College Level Anatomy and Physiology by AudioLearn

COLLEGE LEVEL Anatomy &Physi ology

Anatomy & Physiology

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TABLE OF CONTENTS Preface .................................................................................................................................... 1 Chapter One: Cell Anatomy and Physiology ............................................................................. 5 The Cell Membrane ..................................................................................................................... 5 Cellular Organelles and their Function...................................................................................... 10 DNA, the Nucleus, and RNA ...................................................................................................... 15 Protein Synthesis ....................................................................................................................... 20 Cellular Differentiation .............................................................................................................. 20 Key Takeaways .......................................................................................................................... 22 Quiz............................................................................................................................................ 23 Chapter Two: Body Tissues .................................................................................................... 26 Tissue Organization ................................................................................................................... 26 Types of Tissues ......................................................................................................................... 28 Epithelial Tissues.................................................................................................................... 29 Connective Tissue .................................................................................................................. 35 Muscle Tissue ........................................................................................................................ 39 Nerve Tissue .......................................................................................................................... 41 Key Takeaways .......................................................................................................................... 44 Quiz............................................................................................................................................ 45 Chapter Three: Integumentary System .................................................................................. 48 Layers of the Skin ...................................................................................................................... 48 The Epidermis ........................................................................................................................ 49

The Dermis ............................................................................................................................. 52 The Hypodermis..................................................................................................................... 53 Skin Pigmentation ..................................................................................................................... 54 Accessory Skin Structures ......................................................................................................... 54 The Hair.................................................................................................................................. 55 The Nails ................................................................................................................................ 57 Sweat Glands ......................................................................................................................... 58 Sebaceous Glands .................................................................................................................. 59 Functions of the Skin ................................................................................................................. 59 Disorders of the Skin ................................................................................................................. 61 Skin Coloration Diseases ........................................................................................................ 61 Skin Cancer ............................................................................................................................ 62 Benign Skin conditions........................................................................................................... 63 Key Takeaways .......................................................................................................................... 66 Quiz............................................................................................................................................ 67 Chapter Four: Skeletal System ............................................................................................... 70 Bone Structure and Function .................................................................................................... 70 Types of Bones .......................................................................................................................... 70 Bone Anatomy ........................................................................................................................... 71 Bony Markings ........................................................................................................................... 72 Bony Tissue ................................................................................................................................ 74 Spongy Bone versus Compact Bone .......................................................................................... 76 Bone Growth ............................................................................................................................. 76

Bones and Nutrition .................................................................................................................. 78 Hormones affecting Bone ......................................................................................................... 78 Axial Skeleton ............................................................................................................................ 79 The Cranium .............................................................................................................................. 80 Facial Bones ............................................................................................................................... 83 Inside the Skull .......................................................................................................................... 85 The Hyoid Bone ......................................................................................................................... 86 Vertebral Column ...................................................................................................................... 86 Vertebrae .................................................................................................................................. 87 Coccyx and Sacrum.................................................................................................................... 88 The Intervertebral Discs ............................................................................................................ 88 Ribcage and Sternum ................................................................................................................ 89 Appendicular Skeleton .............................................................................................................. 90 The Scapula and Clavicle ........................................................................................................... 91 Upper Limb ................................................................................................................................ 92 The Pelvic Girdle ........................................................................................................................ 95 The Lower Limb ......................................................................................................................... 96 Joints.......................................................................................................................................... 98 Synovial Joints ......................................................................................................................... 100 Key Takeaways ........................................................................................................................ 102 Quiz.......................................................................................................................................... 103 Chapter Five: Muscles and the Muscular System ................................................................. 106 Types of Muscle Tissue............................................................................................................ 106

Skeletal Muscle Fibers ............................................................................................................. 108 The Neuromuscular Junction and Muscle Contraction........................................................... 109 Muscle Structure ..................................................................................................................... 111 Fascicle Arrangements ............................................................................................................ 112 Muscles of the Head and Neck................................................................................................ 113 Muscles that Move the Head .................................................................................................. 115 Muscles of the Posterior Neck and Back ................................................................................. 115 Muscles of the Trunk ............................................................................................................... 116 Muscles of the Upper Extremity ............................................................................................. 119 Muscles of the Pectoral Girdle ................................................................................................ 119 Muscles of the Lower Extremity.............................................................................................. 124 Key Takeaways ........................................................................................................................ 127 Quiz.......................................................................................................................................... 128 Chapter Six: Central Nervous System ................................................................................... 131 Brain Cell Types and Function ................................................................................................. 131 Types of Neurons .................................................................................................................... 133 Types of Glial Cells ................................................................................................................... 134 Myelin ...................................................................................................................................... 135 Action Potential ....................................................................................................................... 136 Synapses .................................................................................................................................. 139 Neurotransmitters................................................................................................................... 140 Brain Structure and Function .................................................................................................. 141 The Cerebrum ...................................................................................................................... 141

The Diencephalon ................................................................................................................ 143 The Brainstem ...................................................................................................................... 144 The Cerebellum ................................................................................................................... 145 The Ventricles ...................................................................................................................... 145 Blood Supply to the Brain........................................................................................................ 147 Protective Coverings in the Brain and Spinal Cord ................................................................. 148 Spinal Cord Structure and Function ........................................................................................ 148 Key Takeaways ........................................................................................................................ 151 Quiz.......................................................................................................................................... 152 Chapter Seven: Peripheral Nervous System ......................................................................... 155 Basics of the Nervous System ................................................................................................. 155 Glial Cells of the PNS ............................................................................................................... 156 Ganglia ..................................................................................................................................... 157 Peripheral Nerves .................................................................................................................... 158 Cranial Nerves ......................................................................................................................... 158 Spinal Nerves ........................................................................................................................... 161 Sensory Receptors ................................................................................................................... 163 Smell .................................................................................................................................... 166 Hearing ................................................................................................................................ 167 Balance ................................................................................................................................ 169 Touch ................................................................................................................................... 169 Vision ................................................................................................................................... 170 Cranial versus Somatic Nerves ................................................................................................ 173

Generating Motor Responses ................................................................................................. 174 Autonomic Nervous System .................................................................................................... 174 Key Takeaways ........................................................................................................................ 177 Quiz.......................................................................................................................................... 178 Chapter Eight: Endocrine System ......................................................................................... 181 Hormones ................................................................................................................................ 181 Hormone Types ....................................................................................................................... 183 Hormone Pathways and Actions ............................................................................................. 184 Regulation of Hormone Secretion........................................................................................... 186 Pituitary Gland and Hypothalamus ......................................................................................... 188 Posterior Pituitary Gland ......................................................................................................... 189 Anterior Pituitary Gland .......................................................................................................... 189 Adrenal Glands ........................................................................................................................ 191 Thyroid Gland .......................................................................................................................... 193 Parathyroid Glands .................................................................................................................. 194 Pineal Gland ............................................................................................................................ 195 Endocrine Pancreas ................................................................................................................. 195 Secondary Endocrine Organs .................................................................................................. 197 Key Takeaways ........................................................................................................................ 199 Quiz.......................................................................................................................................... 200 Chapter Nine: Heart Anatomy and Physiology ..................................................................... 203 Basic Heart Anatomy ............................................................................................................... 203 Right Atrium......................................................................................................................... 207

Right Ventricle ..................................................................................................................... 207 Left Atrium ........................................................................................................................... 208 Left Ventricle ....................................................................................................................... 208 Electrical Activity of the Heart ................................................................................................ 209 Conduction System of the Heart ............................................................................................. 210 The Electrocardiogram ............................................................................................................ 213 Cardiac Cycle ........................................................................................................................... 214 Cardiac Physiology................................................................................................................... 215 Heart Rate ............................................................................................................................... 216 Stroke Volume ......................................................................................................................... 217 Coronary Arteries .................................................................................................................... 218 Key Takeaways ........................................................................................................................ 220 Quiz.......................................................................................................................................... 221 Chapter Ten: Blood and Blood Vessel Anatomy and Physiology........................................... 224 Blood Components .................................................................................................................. 224 Plasma Components................................................................................................................ 225 Formed Elements in Blood ...................................................................................................... 226 Erythrocytes ......................................................................................................................... 227 Leukocytes ........................................................................................................................... 229 Platelets ............................................................................................................................... 230 Blood Clotting Process............................................................................................................. 231 Blood Typing ............................................................................................................................ 232 Arterial Blood Pressure ........................................................................................................... 232

Regulation of the Cardiovascular System ............................................................................... 233 Nervous System Impact on the Cardiovascular System .......................................................... 234 Endocrine System Impact on the Cardiovascular System ....................................................... 235 Autoregulation of the Cardiovascular System ........................................................................ 235 Pulmonary Circulation ............................................................................................................. 236 Systemic Arteries ..................................................................................................................... 236 Ascending Aorta and Aortic Arch Branches ............................................................................ 238 Thoracic and Abdominal Aorta Branches ................................................................................ 238 Upper Limb Artery ................................................................................................................... 239 Arteries serving the Lower Limbs ............................................................................................ 241 Veins: Anatomy and Physiology .............................................................................................. 242 Upper Body Veins .................................................................................................................... 242 Vein Drainage in the Lower Body ............................................................................................ 245 Hepatic Portal System ............................................................................................................. 245 Key Takeaways ........................................................................................................................ 246 Quiz.......................................................................................................................................... 247 Chapter Eleven: Lymphatic and Immune System ................................................................. 250 Anatomy and Physiology of the Lymphatic System ................................................................ 250 The Immune System ................................................................................................................ 251 Lymphocyte Function .............................................................................................................. 252 Lymphoid Organs .................................................................................................................... 253 The Barrier Mechanisms ......................................................................................................... 256 Innate Immune Responses ...................................................................................................... 257

Natural Killer Cells ................................................................................................................... 258 Recognizing a Pathogen .......................................................................................................... 258 Soluble Factors ........................................................................................................................ 258 Complement System ............................................................................................................... 259 Inflammation in the Immune System...................................................................................... 259 The Adaptive Immune System ................................................................................................ 260 What is an Antigen? ................................................................................................................ 261 T Cell Development and Maturation ....................................................................................... 263 Antibodies and B Cells ............................................................................................................. 264 T Cell-related Antigens ............................................................................................................ 267 Hypersensitivity in the Immune System ................................................................................. 267 Autoimmune Diseases............................................................................................................. 268 Key Takeaways ........................................................................................................................ 269 Quiz.......................................................................................................................................... 270 Chapter Twelve: Respiratory System ................................................................................... 273 Respiratory System Anatomy .................................................................................................. 273 The Nose .............................................................................................................................. 273 Pharynx ................................................................................................................................ 275 Larynx................................................................................................................................... 276 Trachea ................................................................................................................................ 278 Bronchial Tree...................................................................................................................... 278 Alveoli .................................................................................................................................. 278 Lung Anatomy ......................................................................................................................... 280

Pulmonary Ventilation ......................................................................................................... 281 Respiratory Volumes ........................................................................................................... 283 Control of Ventilation .......................................................................................................... 284 Gas Exchange ....................................................................................................................... 285 Ventilation and Perfusion .................................................................................................... 286 Oxygen Transport ................................................................................................................ 287 Carbon Dioxide Transport.................................................................................................... 289 Key Takeaways ........................................................................................................................ 290 Quiz.......................................................................................................................................... 291 Chapter Thirteen: Digestive System ..................................................................................... 294 Structure and Basic Function of the Digestive System ........................................................... 294 Alimentary Canal Histology ..................................................................................................... 295 Nervous System in the GI Tract ............................................................................................... 296 Circulation in the GI Tract ....................................................................................................... 297 The Peritoneum ....................................................................................................................... 297 Process of Digestion ................................................................................................................ 297 Regulation of Digestion ........................................................................................................... 298 Mouth Anatomy and Physiology ............................................................................................. 299 Tongue ................................................................................................................................. 300 Saliva .................................................................................................................................... 301 Teeth .................................................................................................................................... 301 The Pharynx ......................................................................................................................... 302 Esophageal Anatomy ............................................................................................................... 303

Stomach Anatomy and Physiology .......................................................................................... 304 Small Intestine ......................................................................................................................... 308 Large Intestine ......................................................................................................................... 311 Exocrine Pancreas ................................................................................................................... 313 Liver ......................................................................................................................................... 314 Gallbladder .............................................................................................................................. 316 Key Takeaways ........................................................................................................................ 317 Quiz.......................................................................................................................................... 318 Chapter Fourteen: Metabolism and Human Nutrition ......................................................... 321 The Process of Chemical Digestion ......................................................................................... 321 Carbohydrate Digestion .......................................................................................................... 322 Protein Digestion ..................................................................................................................... 323 Lipid Digestion ......................................................................................................................... 323 Nucleic Acid Digestion ............................................................................................................. 324 Nutrient Absorption ................................................................................................................ 324 Metabolism ............................................................................................................................. 326 Catabolic Reactions ............................................................................................................. 326 Anabolic Reactions .............................................................................................................. 327 Hormones that Regulate Metabolism ..................................................................................... 327 Oxidation-Reduction Reactions............................................................................................... 328 Carbohydrate Metabolism ...................................................................................................... 328 Gluconeogenesis.................................................................................................................. 332 Lipid Metabolism ..................................................................................................................... 333

Lipogenesis .......................................................................................................................... 334 Protein Metabolism................................................................................................................. 334 Basic Human Metabolism ....................................................................................................... 335 Nutrition and Metabolism ....................................................................................................... 337 Key Takeaways ........................................................................................................................ 339 Quiz.......................................................................................................................................... 340 Chapter Fifteen: Urinary System .......................................................................................... 344 Urinary Tract Anatomy ............................................................................................................ 344 Ureters ................................................................................................................................. 344 Bladder................................................................................................................................. 345 Micturition Reflex ................................................................................................................ 346 Urethra ................................................................................................................................ 347 Gross Kidney Anatomy ............................................................................................................ 348 Microscopic Kidney Anatomy .............................................................................................. 351 Juxtaglomerular Apparatus ................................................................................................. 353 Proximal Convoluted Tubule (PCT) ...................................................................................... 354 Loop of Henle....................................................................................................................... 354 Distal Convoluted Tubule (DCT)........................................................................................... 354 Collecting Ducts ................................................................................................................... 354 Kidney Physiology .................................................................................................................... 355 Secretion and Reabsorption ................................................................................................ 356 Regulation of Kidney Blood Flow ......................................................................................... 358 Other Kidney Functions ....................................................................................................... 359

Urine Composition .................................................................................................................. 360 Key Takeaways ........................................................................................................................ 362 Quiz.......................................................................................................................................... 363 Chapter Sixteen: Fluids, Electrolytes, and the Acid-Base System.......................................... 367 Fluid Compartments ................................................................................................................ 367 Water and Electrolyte Balance ................................................................................................ 370 Antidiuretic Hormone (ADH) ................................................................................................... 372 Electrolyte Balance .................................................................................................................. 372 Acid Base Physiology ............................................................................................................... 375 The Lungs and Acid-Base Balance ........................................................................................... 376 The Kidneys and Acid-Base Balance ........................................................................................ 377 Acid-Base Disorders................................................................................................................. 378 Key Takeaways ........................................................................................................................ 380 Quiz.......................................................................................................................................... 381 Chapter Seventeen: Male Reproductive System .................................................................. 385 Male Reproductive Anatomy .................................................................................................. 385 The Scrotum......................................................................................................................... 385 Testes ................................................................................................................................... 386 Structure of Formed Sperm ................................................................................................. 389 Sperm Maturation ............................................................................................................... 390 Duct System ......................................................................................................................... 390 Male Reproductive Physiology ................................................................................................ 394 Male Reproductive Development ........................................................................................... 394

Puberty .................................................................................................................................... 395 Key Takeaways ........................................................................................................................ 397 Quiz.......................................................................................................................................... 398 Chapter Eighteen: Female Reproductive System.................................................................. 401 Female Reproductive Anatomy ............................................................................................... 401 The Ovarian Cycle and Oogenesis ....................................................................................... 404 Folliculogenesis.................................................................................................................... 406 Hormones and the Ovarian Cycle ........................................................................................ 407 Fallopian Tubes .................................................................................................................... 409 Cervix and Uterus ................................................................................................................ 409 Menstrual Cycle Physiology .................................................................................................... 410 Breast Anatomy and Physiology .......................................................................................... 411 Female Reproductive Development .................................................................................... 413 Key Takeaways ........................................................................................................................ 414 Quiz.......................................................................................................................................... 415 Chapter Nineteen: Developmental Anatomy and Physiology............................................... 419 Genetics and Development ..................................................................................................... 419 Inheritance Patterns ................................................................................................................ 420 Fertilization.............................................................................................................................. 423 The Zygote ............................................................................................................................... 425 Embryologic Development ...................................................................................................... 426 Pre-Implantation Phase ........................................................................................................... 426 Implantation ............................................................................................................................ 428

Embryogenesis ........................................................................................................................ 430 Placental Development ........................................................................................................... 430 Organ Formation ..................................................................................................................... 432 Fetal Development .................................................................................................................. 433 Key Takeaways ........................................................................................................................ 435 Quiz.......................................................................................................................................... 436 Course Summary ................................................................................................................. 440 Course Questions and Answers ........................................................................................... 444

PREFACE This course is intended to appeal to the undergraduate interested in the complete story on human anatomy and physiology. Through pictures and words, you will study the entirety of the human body, from the cellular/microscopic levels, to the developmental levels, and finally to the macroscopic/anatomic levels of the human body. After talking about cells in general, each body system is discussed in turn so that, by the end of the course, you will feel comfortable regarding your understanding of the form and function of the human body. Chapter one covers the basics of cellular anatomy and physiology. This includes a study of the cell membrane, the cytoplasm of the cell, and the different organelles in the cell. The nucleus is one of the more important organelles of the cell, containing the genetic information in the form of chromosomes and directing cellular functions. Also covered in this chapter is protein synthesis and the differentiation of cells. The topic of chapter two is the formation of body tissues and tissue types. While cells have many similarities, there are differences in structure and function that create different types of tissues. How cells make tissues is covered in this chapter as well as the structure and function of different tissue types, including epithelial, connective, muscle, and nerve tissue. The focus of chapter three in the course is the integumentary system, which is basically the skin. The skin is considered the largest organ of the body, covering most of the external surface of the body. There are several layers, which have different functions. In the dermis of the skin are many different accessory skin structures, which are microscopic in nature. The skin serves several different functions in the body, which are discussed in the last part of this chapter. The skeletal or bone system is the topic of chapter four. The discussion starts with the anatomy and physiology of bone cells and bone tissue. Then the axial skeleton (the skull, spine, and ribcage) is covered in detail as well as the appendicular skeleton (mainly the extremities). The functions of joints and ligaments are discussed as they are important aspects of the skeletal system.

The anatomy and physiology of the muscular system are the topics of chapter five. It begins with a discussion of muscles and tendons as well as the different types of muscle tissue. The muscles of the head, neck, trunk, upper extremities, and lower extremities are also discussed. Chapter six examines the structure and function of the central nervous system. There are different types of brain cells—some of which conduct electricity and others that protect and support the electrically-active nerve cells. The gross anatomy and basic functions of the brain are covered in this chapter as well as the gross anatomy and basic functions of the spinal cord, which is also technically a part of the central nervous system, or CNS. Chapter seven covers the structure and function of the peripheral nervous system. These are the nerves located outside of the brain and spinal cord. The major somatic sensory and motor nerves are covered, including the way the major senses are picked up by the body. The cranial nerves, that do not come from the spinal cord, have unique function, which are discussed. The structure and function of the autonomic nervous system are also covered in this chapter. The focus of chapter eight is the endocrine system. This involves the hormones and their interactions with the various body systems. There are numerous “endocrine” organs both within the brain and outside in the rest of the body. The hypothalamus, the pituitary gland, and the pineal gland are all located near or within the brain. The other endocrine glands covered are the adrenal gland, the thyroid gland, the parathyroid glands, and the endocrine portion of the pancreas. The reproductive hormones are covered in a later chapter on the reproductive system. The anatomy and physiology of the heart are discussed in chapter nine. The heart plays a central role in the cardiovascular system, being the major pump that allows blood to flow through the rest of the body. The cells of the heart (cardiac muscle cells) have a unique electrical activity and synchronize the activity of the chambers of the heart. The coronary arteries are the major arteries supplying the heart; they are important because damage to any of these arteries can potentially cause a heart attack. The discussion of the cardiovascular system continues in chapter ten. There are arteries, veins, and capillaries that allow for blood flow and gas exchange in the tissues after oxygenated blood

is pumped out of the heart and before deoxygenated blood reenters it. The components of blood and blood typing are also an important aspect of the cardiovascular system and are topics in this chapter. The lymphatic and immune system are covered together in chapter eleven in the course. The lymphatic system includes the vessels of the lymphatic system that filter blood and pathogens, making these structures also important to the immune system. The thymus gland is a part of the immune system as well as the spleen. Both of these are discussed in this chapter. The immune system is broadly divided into the innate and adaptive immune system. The cells of the immune system and the physiology of these aspects of the immune system are explained in detail in this chapter. The structure and function of the respiratory system are the main topics of chapter twelve. The respiratory system is broadly divided into the upper and lower respiratory tract. The lower respiratory tract is primarily made up of the lungs and the bronchial tree. The anatomy and physiology of the gas exchanging structures of the lungs (the alveoli) finish up this chapter. The topic of chapter thirteen is the human digestive system. It entails everything in the digestive process from the mouth to the anus as well as several other structures involved in digestion, including the liver, gallbladder, and the exocrine portion of the pancreas. The different anatomical structures included as part of the digestive system are covered in detail, including how they function to take food and turn it into nutrients used by the entire body. Chapter fourteen is a continuation of the digestive system; however, it involves the microscopic and molecular aspects of metabolic processes. Carbohydrate, protein, and lipid metabolism are discussed as well as the important energy-producing process of glucose metabolism. The overall physiology of human nutrition and nutritional needs are also examined as part of this chapter. The topic of chapter fifteen is the urinary system. The urinary tract begins with the kidneys with urine traveling through the ureters, bladder, and urethra. The anatomy and physiology of the kidneys are discussed in this chapter as well as the microscopic anatomy of these structures. Closely connected to the anatomy is the unique physiology of the kidneys. After

the kidneys form urine, this fluid is composed of several smaller molecules, which are discussed in the last part of this chapter. Chapter sixteen covers fluids, electrolytes, and the acid-base system. This includes a discussion of the various fluid compartments in the body as well as how water and electrolytes are balanced by the somatic cells and by the renal system. Acid-base physiology depends on activities of both the lungs and the kidneys, which are examined in this chapter; there are several acid-base disorders that require compensation by both of these systems—also covered in the last part of the chapter. The male reproductive system is the topic of chapter seventeen. It includes coverage of the anatomy of the male reproductive system as well as the physiology (including the male reproductive hormones) involved in this system. Finally, the embryological development of the male reproductive system is discussed. Chapter eighteen examines the female reproductive system. First, the anatomy of the female reproductive system is covered, including the internal and external anatomic structures. The physiology of the menstrual cycle and female hormones are included in this chapter as well as the anatomy and physiology of the female breast. Finally, the embryological development of the female reproductive system is discussed in this chapter. The focus of chapter nineteen is developmental anatomy and physiology. This includes a discussion of genetics and how it applies to human phenotypes. Fertilization is more completely covered than it will be in the previous reproductive system chapters and the development of the embryo is explained in detail. As the embryo becomes a fetus at eight weeks gestation, the development continues; this is covered as the final topic of this chapter.

CHAPTER ONE: CELL ANATOMY AND PHYSIOLOGY This chapter includes a discussion of the cell membrane, the cytoplasm of the cell, and the different organelles that can be found in the cell. The nucleus is one of the more important organelles of the cell, containing the genetic information in the form of chromosomes and directing cellular functions. Also covered in this chapter is protein synthesis and the differentiation of cells.

THE CELL MEMBRANE The cell membrane is primarily composed of lipids, and surrounds the cells of the human body. It defines the cell border and allows the cell to interact in a controlled way with the environment around the cell. Cells need to take in nutrients, eliminate waste and avoid the uptake of toxic or other unwanted substances into the cell. Cell-cell communication is also important and is a function of the lipid membrane. Lipid provide a semi-permeable barrier or membrane between the cell and its environment. It also needs to contain proteins, which help in transport across membranes and cell communication. In addition, there are carbohydrates on the proteins and lipids, allowing for cells to recognize one another. The basic structure of the plasma membrane is referred to as the fluid mosaic model. This means that the phospholipid structure of the lipids (which involves a phosphorus-containing water-loving end and a lipid water-aversive tail) is the main structure in the membrane, with cholesterol and proteins imbedded in and floating throughout the structure. This is a dynamic situation in which the membrane does not look the same from one second to the next. Figure 1 in your guide shows a phospholipid and how it forms a membrane in the cell:

Besides phospholipids, cholesterol, proteins, and carbohydrates are part of the plasma/cell membrane. Let’s look at these in turn in order to understand what the cell membrane looks like: •

The phospholipid is made from a glycerol linkage, two fatty acid tails (which are waterhating or hydrophobic), and a phosphate head group (which is water-loving or hydrophilic). They are arranged in a phospholipid bilayer as is seen in figure 1.

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Cholesterol, which is formed by the fusion of four carbon rings, is lipid that forms part of the core of the membrane. It is less abundant than phospholipids, which make up the majority of the membrane.

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Plasma proteins, which can be loosely attached to the outside or inside of the plasma membrane or can be imbedded partly or completely within the membrane.

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Carbohydrates can be present alone and attached to the outer surface of the cell membrane or are attached to proteins (making glycoproteins) or lipids (forming glycolipids).

Different cells have different proportions of the previously mentioned cell membrane components. Proteins make up 50 percent of the mass of the cell membrane, while lipids of all types make up about 40 percent of the membrane. Ten percent of the membrane by weight comes from carbohydrates. 6

The phospholipid bilayer in the cell membrane formed by these interactions makes a good barrier between the exterior and interior of the cell. It means that polar or positively-charged substances of all sizes have a difficult time crossing the hydrophobic center of the membrane. Phospholipids form a micelle in water, which is a single-layered sphere that keeps out water and other positively-charged substances. Those that are bigger form a bilayer membrane, the largest of which is the cell membrane. There are multiple smaller membranes that form liposomes and other organelles (small cellular organs) inside the cell. Figure 2 shows what a liposome looks like:

There are two types of proteins in the cell membrane: integral and peripheral proteins. Integral proteins are “integrated” into the cell membrane and have at least one hydrophobic segment that can be aligned and in contact with the hydrophobic core of the cell membrane. Some will stick out of either side of the membrane with hydrophilic ends. Trans-membrane proteins extend completely through the plasma membrane. Some integral proteins form channels that allow water-loving ions, water, and other hydrophilic substances to pass through the membrane—usually in a controlled fashion. Figure 3 shows an open and closed membrane channel:

A peripheral membrane protein is found on the inside or outside surface of the cell membrane. They can be attached to phospholipids or to integral proteins in the membrane. They do not have hydrophobic portions that are imbedded in the cell membrane. Instead they are loosely attached to the cell. Carbohydrates are less abundant in the cell membrane. They can be bound to lipids (forming glycolipids) or proteins (forming glycoproteins). These can be branched or straight and consist of up to 60 monosaccharide units that stick out of or inside the cell membrane. These are the main cellular markers that are important in the immune system. They allow the body’s immune cells to recognize self-cells (belonging to the self) and non-self-cells (that do not belong to the cell). The structure of the fatty acid tails of the phospholipids is important in determining how the membrane acts—how fluid it is. Saturated fatty acids have no double bonds (are completely saturated with hydrogen atoms), which makes them straight molecules. Unsaturated fatty acids have fewer hydrogen atoms on them and are kinked. They behave differently in the cell membrane. Saturated fatty acid phospholipids make dense cell membranes, while unsaturated fatty acid phospholipids are less tightly packed and more fluid. Most cell membranes have a mixture of saturated and unsaturated fatty acids.

The transport of substances through the membrane is complex. The membrane transport system is what allows different molecules to enter the cell. There are two types of transport across a membrane: passive transport and active transport. Passive transport does not require energy to function. Molecules will pass from a high to a low concentration in an effort to equalize the concentration on either side of the membrane. Passive transport can involve simple diffusion/passive diffusion, osmosis, or facilitated diffusion. Simple diffusion involves no transporter protein and no energy. Carbon dioxide passes via simple diffusion as does water. The transport stops when the concentration is equalized. Osmosis is the movement of water across the cell membrane. Facilitated diffusion is similar to simple diffusion but requires a transporter protein in order to allow the substance to pass through. These are specific to a certain molecule (although some will transport multiple compounds at the same time). No energy is required for this. Active transport requires both a transporter protein and a continuous supply of ATP or other form of cellular energy. We will talk more about ATP (adenosine triphosphate) but keep in mind it is an energy molecule in the cell. This type of transport can cause molecules to pass from a lower concentration to a higher concentration. A permease or transporter protein will transport amino acids, glucose, organic acids, and inorganic ions (like phosphate, potassium, and sulfate) using energy supplied by the cell. The Na-K (sodium-potassium) pump is an example of an active transport mechanism. Figure 4 is an example of the sodium-potassium ion pump:

There is primary active transport that involves the hydrolysis of ATP to provide energy to directly transport the molecule. The molecule goes from a lower to a higher concentration. In secondary electron transport, energy is released when a molecule goes from a higher to a lower concentration, while the energy released goes into transporting a different molecule across the membrane from a lower to higher concentration.

CELLULAR ORGANELLES AND THEIR FUNCTION The fluid inside the cell is called the cytoplasm. In human cells, cytoplasm is everything between the cell membrane and the nuclear envelope (which encloses the nucleus inside the cell). The cytoplasm consists of a gel-like substance known as cytosol. Cytosol contains numerous ions, different types of small molecules, and large molecules (known as macromolecules). The cytoplasm also contains a cytoskeleton, which is a network of fibers that interlace to form the shape of the cell. The cytoskeleton also keeps the cell structures (organelles) in place within the cell so they can function and interact better with one another. All of the organelles

(tiny organs in the cell) are suspended within the cytoplasm by the cytoskeleton. Figure 5 shows what the cytoskeleton of the cell looks like and how it suspends organelles:

The organelles in the cell have different functions within the cell. There are multiple major organelles and even more minor organelles. Let’s take a look at the different organelles in the cell and what they do: •

Endoplasmic reticulum—this is a continuous but stacked membrane that performs two major functions. The rough endoplasmic reticulum contains ribosomes that are involved in the translation and folding of proteins, while the smooth endoplasmic reticulum helps in the making of lipids in the cell. Figure 6 shows the endoplasmic reticulum in the cell:

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Golgi apparatus—this is a single membrane compartment that helps the cell sort and modify proteins. The proteins come to the Golgi apparatus after being built, but before they go to their destination. This organelle helps in post-translational modification of proteins; it checks them for errors and discards those that are incorrect. The good proteins are packaged and sent for delivery.

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Mitochondrion—this is an organelle that is a double-membrane compartment that is primarily involved in energy production. Later, you will see how this is done biochemically. It has some of its own DNA passed on by the person’s mother. Mitochondria are known as "the powerhouses of the cell." Figure 7 shows what the mitochondrion looks like:

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Nucleus—this is one of the major organelles in the human cell. It is a double-membrane compartment that contains nearly all of the genetic material of the cell and is involved in the maintenance of DNA and in RNA transcription. We will talk more about the nucleus later in this chapter.

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Vacuole—this is a single membrane compartmented organelle that is involved in both storage and homeostasis is the cell. They often store waste products and allow them to exit the cell by fusing with the cell membrane, extruding the waste to the outside of the cell.

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Autophagosome—this is a double-membrane structure that collects different aspects of the material inside the cytoplasm and digests it or degrades it so that the molecules can be broken down and the digested material can be recycled.

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Lysosome—this is a single-membrane structure that is involved in the storage of certain molecules within the cytoplasm. It is also an organelle that degrades certain large macromolecules within the cell. There are some diseases (called lysosomal storage diseases) that affect the ability of the lysosome to degrade certain substances, causing them to build up.

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Centriole—this is made from microtubules (which is a protein involved in the cytoskeleton). It provides an anchor for the cytoskeleton in the cell.

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Cilium—this is made from microtubules as well and is on the outside of the cell. It is found in certain cells of the human body and allows for movement of external medium and other substances located on the outside of the cell. Cells of the bronchial tree, for example, have cilia.

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Myofibril—this will be discussed when muscles are discussed. It is made from bundled filaments and allows for muscle contraction in the cell to occur.

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Nucleolus—this is a structure located inside the nucleus that is involved in the production of ribosomes. It is made from proteins, RNA (ribonucleic acid), and DNA (deoxyribonucleic acid).

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Peroxisome—this is a single-membrane compartment that contains hydrogen peroxide and is involved in the breakdown of hydrogen peroxide in the cell.

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Proteasome—this is a large protein complex that uses proteolysis (protein breakdown) to degrade any damaged or unneeded proteins in the cell.

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Ribosome—this is made from RNA and protein. It is involved in the translation of RNA, which is how proteins are made.

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Vesicle—this is a single-membrane structure that takes up certain molecules and transports the substances to different parts of the cell or outside of the cell.

Figure 8 in the guide shows what the interior of the cell is supposed to look like:

DNA, THE NUCLEUS, AND RNA The nucleus is a double-walled structure inside the cell that contains nearly all of the genetic material in the cell in the form of DNA (deoxyribonucleic acid). DNA is a double-stranded, coiled molecule made up of four different nucleotide bases that together form the instructions to make all of the proteins and enzymes inside the cell and determine what the human or other organism looks like. All of the DNA inside each cell of the body is the same but, through the process of differentiation, the DNA that is “active” inside each cell is unique to the cell type. Figure 9 gives the basic structure of the DNA molecule:

The two DNA strands linked together are called polynucleotides as they are made from simpler “monomeric” molecules known as nucleotides. Each nucleotide is made from one of four nucleobases or nucleosides (called guanine, cytosine, thymine, or adenine), as well as the sugar called deoxyribose, and a phosphate group. Covalent bonds connect the different nucleotides in a specific order that makes up the “alphabet” of the DNA molecule. Hydrogen bonds (which are much weaker) connect the base pairs in the center of the ladder-shaped molecule. Adenine (A) always pairs with thymine (T), while cytosine (C) always pairs with guanine (G). Both strands of nucleotides store the same information. The hydrogen bonds between the base pairs is weak but together they result in a molecule that resists cleavage. When the two strands separate in cell division, a matching strand is created to match with the cleaved strands, creating two identical DNA strands that go to two different daughter cells when the cell divides. The enzymes that assist with this process are DNA replicase, polymerase, helicase, and ligase. More than 98 percent of DNA is “non-coding,” meaning they are DNA sequences that do not specifically code for a known protein. The process of replication, as just described, involves several enzymes and is what makes two DNA molecules out of a single DNA strand. Figure 10 describes the process of DNA replication:

DNA that is coded is referred to as genes. Genes are segments of DNA that are transcribed into ribonucleic acid (RNA), which sends messages via “messenger RNA” or “mRNA” to make certain proteins outside of the nucleus. The nucleobases (or just bases) that make up a gene have their message consisting of a three-base code called a codon. Each combination of three bases codes for a certain amino acid, which is the building block molecule of proteins. Together, the three-base codes are read and translated into a specific sequence of amino acids that make up a specific protein. The process of transcription occurs in the nucleus. It involves slightly separating the DNA strands at a specific gene site and making a “matching” single stranded mRNA molecule that carries the DNA message outside of the nucleus. The enzyme that participates in the transcription process is called RNA polymerase. Figure 11 shows what the process of transcription looks like in the nucleus:

Later, we will discuss the process of translation, which is when the mRNA molecule’s message gets turned into an amino acid sequence to make a protein. Inside the human cell, the DNA is organized into 23 pairs of chromosomes for a total of 46 chromosomes. Twenty-two of these chromosomes are numbered with one coming from the genetic mother and one coming from the genetic father of the individual. There are two unmatched chromosomes in males, the XY chromosome pair (with the Y chromosome coming from the father and the X chromosome coming from the mother). In females, there are two X chromosomes, one from each parent. Figure 12 shows the human karyotype (DNA collection) in male and female humans:

In translation, the mRNA molecule goes to the ribosomes, where protein synthesis takes place. The codons involve 3-letter combinations for a total of 64 possible codons. This is plenty, considering there are just 20 standard amino acids. It means that some amino acids match to more than one codon and that there are three “stop codons” that end the coding region (the TAA, TGA, and TAG codons). Ribonucleic acid or RNA is similar to DNA but is single-stranded and contains slightly different bases. The sugar molecule as part of the RNA strand is ribose instead of deoxyribose as is seen in DNA. The bases include uracil, which replaces thymine in the molecule. There are several different types of RNA, which perform different functions. These include the following: •

Messenger RNA (mRNA)—this is the RNA that is transcribed by DNA and goes on to the ribosome, where it passes the DNA message that makes up the protein.

•

Transfer RNA (tRNA)—this is RNA that attaches to both an amino acid and the mRNA molecule, helping to make the protein strand in the ribosome.

•

Ribosomal RNA (rRNA)—this is RNA that makes up the structural component of the ribosome, which is the protein-making machinery of the cell.

There is also RNA that acts as an enzyme, in which case it is called a ribozyme. It helps to speed a chemical reaction in the cell. RNA also plays important roles in other cellular processes,

including cell differentiation, cell division, and cell aging. Defects in RNA function have been implicated in several human diseases, although the exact defects and diseases have yet to be completely discovered.

PROTEIN SYNTHESIS As mentioned, protein synthesis happens in the ribosome in most cases. Protein synthesis is occuring all the time and involves taking the DNA message in the gene, transcribing it onto a mRNA molecule, and then taking the mRNA molecule out to the ribosome. There, the message on the mRNA molecule is coupled with multiple molecules of transfer RNA. The amino acid sequence is put together by the tRNA molecule and enzymes, so that a naked strand of protein is made. The naked strand is the “primary structure” of the protein. It has not undergone any modification. After it is made, it undergoes post-translational modification. This involves changing the primary structure of the protein strand so that it can make bonds between different amino acids and can fold into a three-dimensional shape. The 20 standard amino acids can be expanded by modifying an existing functional group on an amino acid or introducing a new one such as phosphate. Phosphorylation is a common event in controlling the activity of enzymes and is the most common post-translational modification that happens to the protein strand. The ends of the protein chain can be connected to one another and segments of protein can be cleaved in order to activate the protein from the proprotein—the protein precursor molecule. Other things that can happen in post-translational modification include acetylation, hydrogen bonding, and disulfide bonding.

CELLULAR DIFFERENTIATION Cellular differentiation involves the process of taking a less specialized cell and turning it into a more specialized cell type. While all cells have the same DNA, the cells undergo a differentiation process to make a multicellular organism. Differentiation occurs as soon as the

single-celled human zygote begins to divide. After several cell divisions, differentiation starts to occur. When differentiated daughter cells divide themselves, they divide into cells that are either identical to the cells they divide from or differentiate further until fully differentiated cells are created. Stem cells are not differentiated and that make fully-differentiated daughter cells in the adult human. The most commonly-known stem cells are those that make the different types of white blood cells or red blood cells in the body. These are called hematopoietic stem cells. A differentiated cell can have a different size, a different shape, modified metabolic activity, and varying external markers on them when compared to the stem cell. These changes are largely due to alterations in the gene expression of the differentiated cell. The DNA sequence does not change but certain genes are turned on or turned off in the differentiated cell to make the cell different from its precursor. A cell that can turn into many different cell types is called a pluripotent stem cell, while a cell that can differentiate into all other types of cells is called a totipotent stem cell. Only the zygote and very early embryonic cells are truly totipotent. After a few differentiations, the resulting cells lose this ability and become less and less pluripotent.

KEY TAKEAWAYS •

The cell membrane surrounds and defines the cell; it is important in cell-cell communication, cell identification, and controlling what goes into and outside of the cell.

•

The cell membrane is made up of a phospholipid bilayer, proteins, carbohydrates, and cholesterol.

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There are numerous major and minor organelles that function in the body to perform all of the cell’s functions; they are suspended in the cell by the cytoskeleton.

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The DNA molecule makes up the genetic material of the cell.

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Through the processes of transcription and translation, the DNA message goes on to create protein molecules.

•

Through cell differentiation, cells that are less differentiated go on to become increasingly differentiated by turning on or turning off certain genes in the cell.

QUIZ 1.

Which is not considered a function of the cell membrane? a. Cell-cell communication b. Nutrient uptake c. Nutrient metabolism d. Waste excretion Answer: c. The cell membrane does each of these things but does not participate in nutrient metabolism. It takes in nutrients and eliminates waste; it is important in cell-cell communication.

What structure makes up the majority of the plasma membrane? a. Protein b. Phospholipid c. Cholesterol d. Glycolipid Answer: a. Phospholipids and the phospholipid bilayer makes up the majority of the molecules of the plasma membrane but protein makes up 50 percent of the membrane by weight.

Which molecule passes through the cell membrane via simple diffusion? a. Carbon dioxide b. Sodium c. Potassium d. Amino acids Answer: a. Gases like carbon dioxide and water pass through the cell membrane via simple diffusion. The others require a protein or another transport mechanism to pass through the cell.

Which cellular organelle is involved in energy production in the cell?

a. Endoplasmic reticulum b. Golgi apparatus c. Vacuole d. Mitochondrion Answer: d. The mitochondrion makes ATP energy to supply cell with the energy it needs throughout the rest of the cell. 5.

Which organelle is responsible for packaging proteins for export—acting like the “post office” in the cell? a. Nucleolus b. Endoplasmic reticulum c. Golgi apparatus d. Peroxisome Answer: c. The Golgi apparatus finalizes the protein structure formation, discards “bad” proteins and packages the proteins so they go to the proper places.

What molecule is not part of the DNA nucleotide? a. Nucleoside base b. Ribose c. Deoxyribose d. Phosphate Answer: b. Ribose is the sugar that makes up ribonucleic acid or RNA but is not the sugar structure that is part of the DNA molecule (which is called deoxyribose).

After transcription occurs, what is the molecule that is created? a. DNA b. Protein c. Amino acid

d. mRNA Answer: d. Messenger RNA or mRNA is the end-product of transcription in the cell nucleus. 8.

Which enzyme is specifically involved in the transcription process? a. RNA polymerase b. DNA replicase c. DNA helicase d. DNA ligase Answer: a. RNA polymerase is responsible for transcribing a segment of doublestranded DNA into a single stranded mRNA molecule.

What type of ribonucleic acid (RNA) is responsible for putting the amino acids together in the ribosome? a. mRNA b. rRNA c. Ribozymes d. tRNA Answer: d. The tRNA is directly responsible for putting the amino acids together to make the protein molecule.

10.

Where in the cell does translation normally take place? a. Nucleus b. Ribosome c. Nucleolus d. Smooth endoplasmic reticulum Answer: b. The protein-making factory where translation takes place is normally in the ribosome.

CHAPTER TWO: BODY TISSUES While cells have many similarities, there are differences in structure and function that create different types of tissues. How cells make tissues is covered in this chapter as well as the structure and function of different tissue types, including epithelial, connective, muscle, and nerve tissue.

TISSUE ORGANIZATION There are more than two hundred different cell types in the human body. Remember that each cell in the body contains the same DNA but, by turning on and off certain genes in the cell, the different cell types emerge. At some point, the cells become irreversibly committed to being of a certain cell type. In general, the cells of the same type have junctions between the cells so that the tissue is organized and so that it maintains a specific shape. The cells communicate with one another so that the tissue has a specific function through the connections they have. Hormones and similar molecules will act at a distance to have a tissue type act as a unit when the tissue is too large for intercellular communication to take place. The term “tissue” is used to talk about a similar group of cells located together in the body. In general, these cells share the same embryonic origin (which will be discussed in a later chapter). These cells share structural features and are arranged in an orderly manner so that the tissue can function as a whole. Humans, have multiple tissue types that work as a whole and that interact with other tissue types in the body. Tissues have cells that adhere to one another through intercellular junctions, which allow cells to both adhere to and communicate with one another. Epithelial cells have a particularly strong attachment to one another because they form barrier functions and must survive mechanical forces.

There are three different intercellular junction types—each of which has a different function. These include the following: •

Tight junctions—these are also referred to as occluding junctions. There is a band of protein molecules that encircle the connecting cells, forming a tight seal between the cell membranes. They are also referred to as “zonula occludens.” There is still transport between the cells but there is no passive flow between the cells.

•

Adherent junctions—these are referred to as anchoring junctions and include structures called “desmosomes” and “hemidesmosomes”. Most anchoring junctions are referred to as “zonula adherens.” They strengthen the tight junctions and help to link the cytoskeletons of adjacent cells. Desmosomes are referred to as “macula adherens,” which are disc-shaped structures that form a dense attachment of anchoring proteins between two cells. Figure 13 shows what a desmosome looks like:

Hemidesmosomes are found at the base of an epithelial cell and attach the cell to the basal lamina beneath the epithelium. •

Gap junctions—these consist of the connexin protein and allow for the direct exchange of both nutrients and intercellular signals between adjacent cells. Larger molecules can be exchanged through these hollow connections. They are found along the lateral surfaces of an epithelial cell, establishing the communication between cells.

While there are numerous specific tissue types, they can be organized into four basic categories of tissues. These include connective, epithelial, muscle, and nervous tissue. We will talk about each of these tissue types and how they function in the body.

TYPES OF TISSUES One of the four main types of tissue in the body is epithelial tissue or “epithelium.” This is what covers the entire surface of the body and the lining of most of the body’s internal cavities. Its functions include secretion, absorption, protection, and filtration. The skin on the outside of the body is epithelium; it protects the body from dust, dirt, bacteria, and microbes. The cells can be thin (as they are on the outermost layers), flat, elongated or cubic in their structural nature. These cells have many junctions, in keeping with their function. The most abundant tissue in the body is connective tissue—found everywhere in the body. This type of tissue is responsible for the support and protection of all of the organs and tissues of the body. Included as connective tissue are fatty tissue, loose connective tissue, dense fibrous tissue, bone, lymph tissue, cartilage, and blood. Muscle tissue comes in three types: skeletal, smooth, and cardiac muscle. Of these, only skeletal muscle is voluntary—used to control the skeletal parts of the body. Smooth muscle is found in the walls of the blood vessels and the internal organs of the body. It is completely involuntary. Cardiac muscle is found in the walls of the heart and acts as the “pumping tissue” of the heart. It is also involuntary. All types of muscle tissue are excitable electrically. Nerve tissue is found in the brain and in all parts of the body. Most nerve cells are long and stretch to connect to other nerve cells using chemo-electrical signaling between the cells. 28

Impulses come from the periphery of the body and are interpreted by the brain, while the brain nerve cells and nervous tissue send signals to the periphery of the body, telling the muscles and other tissues of the body to do certain things. All nerve tissue, like muscle tissue, is excitable electrically.

EPITHELIAL TISSUES Epithelial tissue is also referred to as epithelium. Its function is to protect the lining of blood vessels, the inner aspect of most organs, and the outermost layer of the body—the skin. The way that epithelial tissue is defined is mainly according to shape. The three main shapes seen in this type of tissue is 1) squamous, 2) columnar, and 3) cuboidal. It can also be multi-layered or in a single layer. Multi-layered squamous tissue is called “stratified.” There is also “pseudostratified” epithelium, which looks stratified but is actually a single layer. Figure 14 shows the different shapes that epithelial tissue can take:

It should be noted that all glands are made from epithelial cells. In such cases, the epithelial cells function as secretory cells. Other functions of epithelial cells include selective absorption, sensing, transcellular transport, and protection. Nourishment of epithelial cells does not come from having a blood supply. The basal lamina or basement membrane, which is part of the

connective tissue, must be permeable enough to allow nutrients to pass through in order to reach the cells of the epithelium. There are multiple different types of epithelial tissue, including these: •

Simple squamous epithelium—this is a single flat layer of cells. It is thin in order to have materials to pass through via filtration and diffusion. It also is capable of secreting a lubricating substance. This type of epithelium is found in the air sacs of the lungs, the blood vessel lining, the lining of the heart, and the lining of the lymphatic vessels. Figure 15 shows what simple squamous epithelium looks like:

•

Simple cuboidal epithelium—these cells are square on histologic (microscopic) evaluation. Its function is absorption and secretion. It is found in ducts and in the secretory parts of the small glands. It is the lining of the tubules of the kidneys. Figure 16 shows what simple cuboidal epithelium looks like:

•

Simple columnar epithelium—this is epithelial tissue that mainly absorbs other molecules. It will also secrete enzymes and mucus. It is mainly found ciliated (with cilia on the outer surface) in bronchial tissue, the uterus, and the fallopian tubes. It is found without cilia in the bladder and the digestive tract. Figure 17 is what simple columnar epithelium looks like:

•

Pseudostratified columnar epithelium—this looks stratified or layered because the nuclei do not line up in a straight line. Its function is to secrete and/or move mucus. It is the type of epithelial tissue seen lining the trachea and most of the upper respiratory tract. It is generally ciliated (meaning that there are cilia on the surface).

•

Stratified squamous epithelium—this is layered but otherwise flat tissue that, as the major function, protects underlying tissue from abrasive actions. It is the tissue that lines the mouth, the vagina, and the esophagus.

•

Stratified cuboidal epithelium—this tissue is also protective to underlying tissue. It forms the sweat gland lining, salivary glands, and mammary glands (the breast tissue).

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Stratified columnar epithelium—this is both secretory and protective to underlying tissue. It lines the male urethra and some glands in the body.

•

Transitional epithelium—this is irregularly shaped stratified tissue that lines the bladder, urethra, and ureters. Its function is to allow the tissue it protects to be flexible and to stretch.

As mentioned, epithelial cells are identified by shape. The squamous epithelium is flat and scale-like. The cuboidal epithelium is roughly square when viewed with a microscope. The columnar epithelium is tall and thin (and sometimes ciliated). They can be simple or stratified. The pseudostratified epithelium is actually one-layered but does not appear that way because the nuclei are seen at different heights on histology examinations. Figure 18 shows what pseudostratified columnar epithelium looks like:

Simple epithelium involves a single layer of cells. Each cell is in contact with the basal lamina (also called the basement membrane), which separates the epithelial layer from underlying connective tissue. It is primarily involved in filtration and absorption. Pseudostratified epithelium also counts as a type of simple epithelium, even though it least looks like it. Both simple columnar and pseudostratified epithelial tissue can be ciliated or non-ciliated. Ciliated pseudostratified epithelium is also called “respiratory epithelium” because it is found only in the nasal cavity, trachea, and bronchi.

As mentioned, stratified epithelium is multilayered in nature. It is multilayered because it is needed to withstand either chemical or mechanical insults. Layers can be abraded or swept away by chemical exposure without losing the deeper layers. They tend to be flat cells at the apical (uppermost) layer of the stratification and more cuboidal or columnar near the base of the layer. The stratified epithelial tissue has the following specialization types: •

Keratinized epithelium—this is when the most apical layers of epithelium involve dead cells that lose their nucleus and cytoplasm. Instead they contain keratin, which is an extremely tough and highly resistant protein. It waterproofs the epithelium and is mainly seen in skin. Moist stratified epithelium without keratin is seen as the type of epithelium in parts of the esophagus.

•

Parakeratinized epithelium—this is similar to keratinized epithelium in that keratin is seen in the apical layers; however, the nuclei are still seen in the cells at the apex of the tissue. This is the type of epithelium seen in the mouth and upper areas of the esophagus.

•

Transitional epithelium—this is specifically found in areas of the body that need to stretch. It looks like stratified cuboidal epithelium when the area is relaxed and stratified squamous epithelium when the area is distended. This is referred to as “urothelium” because it is found in the ureters, bladder, and urethra.

Squamous epithelium looks like thin, flat plates, which provide a smooth, low-friction surface that allows fluids to flow freely over the tissue. The nuclei, like the cells are flattened and oval in shape. These types of cells are typically found in the skin and alveoli (as a simple membrane). The endothelium of the blood vessels and the pericardium consist of these types of cells. Cuboidal epithelium involves cube-shaped cells. The cell nucleus tends to be large and spherical—located in the middle of the cell. It is commonly found as part of exocrine glands and generally secretory in nature or, in the case of the kidneys, it is absorptive. It is also found in the female ovaries and seminiferous tubules in the testes. Stratified cuboidal epithelium is seen in the ducts of the mammary glands, sweat glands, and salivary glands. 33

Columnar epithelial tissue involves column-shaped cells that have a height at least four times of the cell width. The nuclei are located at the bases of the cells and are elongated. Commonly seen in the stomach and intestines, the cells will have microvilli that maximize their apical surface area for better absorption. Ciliated borders are seen in the uterus, the central canal of the spinal cord, and the fallopian tubes. There are specialized columnar cells for sensation in the nose, taste buds, and ears. Goblet cells are specialized columnar cells in the duodenum, which secrete mucus for lubrication. Stratified columnar cell epithelial tissue is uncommon but can be seen in the salivary glands, pharynx, eye, and reproductive organs. Pseudostratified epithelium is often ciliated. The cilia will use energy to beat in unison in order to propel debris through and out of the respiratory tract. Mucus is secreted to lubricate the tissue. In the uterus and fallopian tubes, the ciliated pseudostratified epithelium will propel the fertilized egg from the ovaries to the uterus. The key features of epithelial tissue are that there are almost no intercellular spaces because they are tightly packed and connected with tight junctions and that there is a basement membrane that separates the epithelial tissue from underlying connective tissue. The basement membrane is a scaffolding substance that supports the epithelium. There is a nerve supply but no blood supply to epithelial tissue and the basement membrane acts like a semipermeable membrane that decides what substances will be allowed through and what will not. Epithelial tissue comes from all three of the germ layers of the embryo. This will be discussed more in the last chapter. The ectodermal germ layer goes to make the epidermis; the mesodermal germ layer goes to make the lining of the body cavities; and the endodermal germ layer goes to make the lining of the GI tract. These make the various epidermal layers different from a pathological perspective so that cancers of both the mesothelium and endothelium to be sarcomas, with ectodermally-derived epidermis to be carcinomas. The main functions of epithelial tissues in the body include the following: •

Protecting underlying tissues (from trauma, pathogenic invasion, toxic exposures, drying, and irradiation)

•

Exchange and regulation of chemicals across their surface (from the body cavity to the connective tissue beneath the epithelium) in the act of absorption

•

Secretion of hormones, sweat, enzymes, and mucus by means of ductal systems

•

The provision of sensation

Special epithelium is used to make glandular tissue. There are two types of glands that are made from epithelial tissue. The first is endocrine glands, which secrete hormones into the bloodstream. The second is exocrine glands, which secrete mainly enzymes (but also other products) through ducts that deliver the products into another organ system.

CONNECTIVE TISSUE Connective tissue is developmentally derived from the mesoderm and found throughout the body as it mainly provides support to other tissues. There are four main components to connective tissue: •

Fibers—which can be collagen or elastin protein molecules that support the cells

•

Ground substance

•

Cells—these can be adipocytes (fat cells), macrophages, mast cells, fibroblasts, and leukocytes

•

Water—this is what all of these cells are suspended in

While blood and lymph are technically considered connective tissue, they lacks fiber so some experts do not include these as being true connective tissue. Figure 19 shows what a basic connective tissue would look like:

Connective tissue is subdivided into regular and special connective tissue. Connective tissue proper is even further subdivided into loose connective tissue, dense irregular connective tissue, and dense regular connective tissue. These are labeled as such depending on the amount of fibrous tissue and ground substance in the tissue, with loose connective tissue having more ground substance than dense connective tissue. Dense regular connective tissue involves things like ligaments and tendons, which have a great deal of densely-packed and orderly collagen fibers in them so that they have a great deal of tensile strength but only in one direction. On the other hand, dense irregular connective tissue has tensile strength in multiple directions because of interweaving and irregularity of the fibrous tissue. Special connective tissue involves blood, reticular connective tissue, bone, cartilage, and adipose tissue. Granulation tissue involves newly formed tissue that builds up inside a wound as it starts to heal; this is also connective tissue. The main characteristics of connective tissue include the following: •

There is ground substance, which is a clear, viscous fluid that contains proteoglycans and glycosaminoglycans. It affixes water in the tissue and makes up the intercellular space. One of its roles is to slow the spread of extracellular pathogens.

•

Cells are dispersed throughout the extracellular fluid matrix.

•

Fibers (in some connective tissue), which are mainly collagen and elastin. Blood contains no fibers but the cells are suspended in plasma.

•

The matrix of the connective tissue includes both the ground substance and the fibrous components.

There are three major types of fibers seen in connective tissue, including the following: •

Collagenous fibers—these bind the connective tissue (including bone) together and are found in the intervertebral discs, gut, blood vessels, bone, cartilage, tendons, ligaments, corneas, and skin. Figure 20 shows what collagen fibers are made from. These are biochemically made from alpha-polypeptide chains.

•

Elastic fibers—these allow different organs of the body, such as the lungs and arteries, to recoil and have elasticity. They are found in the extracellular matrix of these organs and are made from elastin and elastic microfibrils. Figure 21 shows what elastin and collagen look like together in connective tissue.

•

Reticular fibers—these are made from type III collagen and are used to form a scaffold for the cells of the connective tissue. They are found in the lymphatic organs, bone marrow, and liver.

There are many different functions for the connective tissue. The loose and dense irregular connective tissue types are formed by fibroblasts and play a vital role in allowing nutrients and oxygen to diffuse from the capillaries (blood supply) to the cells of the tissue. In the same way, carbon dioxide and waste products are allowed to diffuse out of the cells, through the tissue, and into the bloodstream. Dense regular connective tissue tends to form distinct structures. These include aponeuroses, ligaments, and tendons, which are very strong, as well as the cornea, which is a specialized part of the eye. In the blood and lymph tissue, reticular fibers (which are made by reticular cells) provide the matrix (called the parenchyma) for many major organs. In the umbilical cord, there is mucous connective tissue that surrounds the vessels of the cord. There are many disorders of connective tissue that are beyond the scope of this course. Genetic diseases, such as Marfan syndrome and Ehlers-Danlos syndrome, are genetic disorders that affect the elasticity of the connective tissue. Cancers of connective tissue are called sarcomas. Several autoimmune diseases affect the connective tissue, including lupus. Scurvy (a vitamin C deficiency state) affects collagen synthesis in the connective tissue.

MUSCLE TISSUE Muscle tissue is a type of soft tissue in the body. It is by definition contractile tissue and is formed by the process of myogenesis in the embryo. As mentioned, the three types of muscle tissue include skeletal (striated) muscle, smooth (nonstriated) muscle, and cardiac (semistriated) muscle. Figure 22 shows what these different muscle types look like:

There is no conscious control over smooth muscle and cardiac muscle but there is activation of both muscle types by the central nervous system and the endocrine system. The contraction of skeletal muscle is voluntary with input from the central nervous system. Deep tendon reflexes (like the knee-jerk reaction) will happen involuntarily but depend on the central nervous system without actual thinking involved. Muscle cells are contractile and are called myocytes. They can be very short muscle cells or as long as ten centimeters in length. They can be connected by arrangements of myofilaments, which are regularly repeated to allow the muscle tissue to have definition. Skeletal muscle is anchored by tendons or aponeuroses to bone as is used to cause skeletal movement and to affect a certain posture. About 40 percent of the body by mass is made from skeletal muscle. It is known for striations. Smooth muscle is non-striated and is found within the walls of internal structures, such as the stomach, esophagus, bronchi, intestines, bladder, urethra, ureters, blood vessels, and the arrector pili in the skin (which makes goosebumps). Cardiac muscle is also striated and is found in the heart. Both cardiac and skeletal muscle contains sarcomeres, which are packed bundles into bundles of muscle. Sarcomeres are made from long, fibrous proteins that act as filaments that slide past one other when a muscle contracts or relaxes. Skeletal muscle has parallel bundles of cells,

while cardiac muscle has intercalated discs that connect the striations and non-parallel angles. Smooth muscle can contract continuously, while skeletal muscle contracts in bursts. Skeletal muscle is the only type of muscle that connects to nerves via a neuromuscular junction, which will be discussed in a later chapter. The fibers are cylindrical and long in skeletal muscle, branching in cardiac muscle, and very short and fusiform in smooth muscle. There are multiple nuclei in skeletal muscle but not in other muscle types. Cardiac muscle is highly self-regulated with a rapid response, while smooth muscle has a slow but spontaneous response. Only skeletal muscle is not self-regulated (relying on the neuromuscular junction). There are two types of skeletal muscle: Type 1 (slow twitch) muscle and Type 2 (fast twitch muscle). There are several types of fast twitch muscle fibers. Slow twitch muscle has many capillaries and myoglobin, which gives the muscle its red coloration. It carries more oxygen and has sustained aerobic activity. Type IIa muscle is aerobic and looks red in color like Type 1 muscle. Type 2x muscle is less dense in mitochondria and myoglobin. It is the fastest muscle type in humans and is more forceful than other skeletal muscle but cannot sustain itself. Type 2b muscle is not found in humans and is pale in color. It is the fastest type of skeletal muscle (found in rodents). Smooth muscle is divided into single and multi-unit types. Single unit types will contract as a syncytium (which is a multinucleated mass that isn’t separated into separate cells). Multi-unit smooth muscle will allow for finer control and gradual responses because each separate muscle is innervated separately so that, ultimately, the tissue contracts as a whole but with a graded response. Smooth muscle is divided into the types of things it supplies. For example, the smooth muscle that is found in the blood vessel walls is called vascular smooth muscle. One type is the tunica media layer seen in the vessels, while another is called uterine smooth muscle (because it is the myometrium or muscle layer of the uterine cells). The iris of the eye has smooth muscle (called the ciliary muscle). There is similar smooth muscle in the respiratory tract, bladder, lymph tissue, and in the skin (the arrector pili). The mesangial cells in the glomeruli of the kidneys are very similar to smooth muscle cells.

Cardiac muscle is the basic foundation of the heart, called the myocardium. The muscle is made from cardiomyocytes that contain a single nucleus (most often). The myocardial layer of the heart is separated from two other layers: the epicardium around the outside of the heart and the endocardium on the inner layer of the heart. The muscle cells act in coordination to pump blood out of the atria and ventricles to either the systemic or pulmonary circulatory systems. When these muscle cells contract, it is during “systole” and when they relax, it is during “diastole.” The cardiac muscle is supplied by ordinary smooth muscle-containing arteries called coronary arteries.

NERVE TISSUE Nerve tissue is also referred to as neural tissue. It is the main tissue aspect of the nervous system. It consists of the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS is the brain and spinal cord, while the PNS is everything outside of those structures. The tissue is made of neurons (which receive and transmit electrical impulses) and neuroglia or glial cells, that provide nutrients to the neurons and that assists in the propagation of the nerve impulse. There are four types of neuroglial cells in just the CNS, including microglial cells, astrocytes, oligodendrocytes, and ependymal cells. In the PNS, the two types of neuroglia are called Schwann cells and satellite cells. In the CNS, the tissue is broken down into gray and white matter. The white matter contains myelin (which is white in color), while the gray matter consists of mainly neuron cell bodies (which is gray in color). Neurons are specially designed to receive and carry electrical nerve impulses, which are called “action potentials.” The impulse is carried from one cell membrane to the next via chemical molecules called neurotransmitters. They have a large cell body (called a “soma”), with two types of projections, called dendrites and axons. The dendrites generally receive the impulse and there are usually many per cell. The axon is usually one per cell and it carries the impulse to the next cell (although there are exceptions). The space between the two nerve cells is called the “synapse” or the synaptic cleft.

There are structural and functional classifications for the different nerve cells. The three cells in the functional classification include: •

Sensory neurons—these are also referred to as afferent neurons. They relay the sensory information from the periphery of the body to the central nervous system.

•

Motor neurons—these are also referred to as efferent neurons. They relay an action potential out of the CNS to the proper part of the exterior of the body, such as a gland or muscle.

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Interneurons—these are neither afferent nor efferent. They form connections between neurons in either the brain or spinal cord.

There are four different neuron cell types in the structural classification of nerve cells. These include the following: •

Multipolar neurons—these will have at least three processes coming off of the soma and are the major type of neuron seen in the CNS, found either as motor neurons or interneurons.

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Bipolar neurons—these have just two processes coming off the soma, which include just one dendrite and one axon.

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Pseudounipolar neurons—these are sensory neurons that have a cell body that has a single process that splits into two separate branches. One is the axon and the other is the dendrite.

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Unipolar brush cells—these are excitatory interneurons that have one short dendrite that ends in a tuft of structures called dendrioles. These are found in the cerebellum of the brain.

As mentioned, there are also neuroglia as part of the neural tissue. They tend to be much smaller than neurons and have different functions. The different types of neuroglial cells include the following:

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Microglia—these are macrophage cells that act as the main immune system for the central nervous system.

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Astrocytes—these are star-shaped and large, making up the most abundant type of cell in the central nervous system.

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Oligodendrocytes—they have few processes and function to make the myelin sheath that allows axons to transmit impulses at such rapid speeds.

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NG2 Glia—these are developmental precursor cells to the oligodendrocytes but have no other major function.

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Schwann cells—these are the “oligodendrocytes” of the peripheral nervous system and help to maintain axons by forming the myelin sheaths of the axons of the PNS.

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Satellite glial cells—these line the surface of the neuron cell bodies in the ganglia, which are groups of nerve cell bodies in the peripheral nervous system.

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Enteric glial cells—these are found in the enteric nervous system, which lies within the confines of the gastrointestinal tract.

Each nerve has connective tissue surrounding and supporting it. The connective tissue is made of three layers. The endoneurium is the inner layer, which is thin and delicate. The perineurium is the layer that coats the axon and consists of 7-8 concentric layers that serve to protect the nerve fibers, preventing large molecules from getting into the nerve cell. The epineurium is the outermost layer of connective tissue around the neuron. It is thick and dense, making up the thick layer that is seen when one looks at a peripheral nerve. The main function of the nervous tissue is to provide communication and messages to and from the brain and body, conducting electrical signals across the nerve tissue. The gray matter contains the synapses and the white matter contains the axons (which are myelinated). The ganglion tissue in the PNS contains the cell bodies and dendrites of many nerve cells, containing relay points for the nerve tissue impulses to pass from cell to cell.

KEY TAKEAWAYS •

Tissues are the next organization level above cells. Tissues are arranged into organs and organs are arranged into body systems.

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Cells are connected or communicate with one another through intercellular connections.

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The main tissue types are epithelial, nerve, muscle, and connective tissue.

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Epithelial tissue tends to be single or multi-layered and line or cover the organs of the body.

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Connective tissue supports the body and is found in all parts of the body.

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The three types of muscle tissue are skeletal, smooth, and cardiac muscle.

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Nerve tissue consists of conducting neurons and non-conducting glial or neuroglial cells.

QUIZ 1. Which tissue type has the greatest degree of intracellular connection? a. Muscle tissue b. Connective tissue c. Nerve tissue d. Epithelial tissue Answer: d. Epithelial cells need to withstand shear forces and form barriers in the body so that they require the strongest intracellular connections when compared to other tissue types. 2.

What type of intercellular junction allows for communication and exchange of nutrients between two epithelial cells? a. Gap junctions b. Adhering junctions c. Tight junctions d. Desmosomes Answer: a. Gap junctions form pores between two cells to allow nutrients and messenger molecules to travel to adjacent cells.

Which muscle is considered voluntary? a. Intestinal muscles b. Neck muscle c. Heart muscle d. Aortic muscle Answer: b. The muscles of the neck are voluntary muscles that help turn the neck in all directions under the individual’s control.

Which type of tissue is not considered electrically excitable? a. Cardiac muscle 45

b. Nervous tissue c. Smooth muscle d. Glandular tissue Answer: d. Each of these types of tissue are considered electrically excitable except for glandular tissue, which is not able to be electrically stimulated. 5.

What body area does not contain ciliated columnar epithelium? a. Bronchi b. Uterus c. Fallopian tube d. Mouth Answer: d. The bronchi, fallopian tubes, and uterus all contain ciliated columnar epithelium; however, the mouth does not.

Which type of epithelial tissue is found lining the mouth? a. Stratified columnar b. Stratified squamous c. Simple columnar d. Transitional Answer: b. The stratified squamous epithelium of the mouth protects it from abrasion and other mechanical forces.

In which area of the body can transitional epithelium be found? a. Upper esophagus b. Stomach c. Kidneys d. Bladder Answer: d. As transitional epithelium is necessary for stretching, it is found in the bladder so that stretching can occur in this tissue type.

Which type of epithelial tissue is found in the alveoli of the lungs? a. Squamous b. Cuboidal c. Columnar d. Pseudostratified Answer: a. There is simple squamous epithelium in the alveoli. These thin cells are necessary because the carbon dioxide and oxygen need to cross through these cells as part of gas exchange.

Which type of cells are contractile in normal muscle tissue? a. Reticular cells b. Fibroblasts c. Lymphocytes d. Myocytes Answer: d. The myocytes are the main cells that make up muscle tissue. They are contractile and allow for the muscles to contract.

10.

What is only a feature of cardiac muscle and not of smooth and skeletal muscle? a. Intercalated discs b. Sarcomeres c. Striations d. Multiple nuclei Answer: a. Cardiac muscle has striations that do not run parallel to one another. The muscle bundles angle off from one another by means of intercalated discs, which are not a part of either skeletal or smooth muscle.

CHAPTER THREE: INTEGUMENTARY SYSTEM The focus of this chapter is the integumentary system, which is basically the skin. The skin is considered the largest organ of the body, covering most of the external surface of the body. There are several layers that make up the skin, which have different functions. In the dermis of the skin are many different accessory structures, which are microscopic in nature. The skin serves several different functions in the body, which are discussed in the next part of this chapter.

LAYERS OF THE SKIN As mentioned, in medical terms, the skin is considered an organ because it is made from the same basic tissues (all over the body) and because the skin performs a unique function, separate from other organs in the body. There are multiple layers to the skin, which are held together by connective tissue. The deeper layers are highly vascularized and send nutrients up to the higher layers by means of diffusion. Figure 23 shows the basic skin layers:

There are two basic layers of the skin: the epidermis and the dermis. Many anatomists will also include the hypodermis as a third, deeper layer that is highly associated with the skin.

THE EPIDERMIS The epidermis is exclusively epithelial tissue, meaning it does not have blood vessels and has a basement membrane or basal lamina. There are four to five different layers to the epidermis, depending on the part of the body being covered. Figure 24 shows what the epidermal layers look like:

The four-layered skin is thinner than five-layered skin. Parts of the body with four layers have (from deep to superficial) the following layers: the stratum basale, the stratum spinosum, the stratum granulosum, and the stratum corneum. The fifth layer of skin is only seen on the soles of the feet and the palms of the hand. This layer is called the stratum lucidum (which is located between the stratum corneum and the stratum granulosum). The layers of the epidermis all contains keratinocytes except for the stratum basale layer. A keratinocyte is defined as a cell that both makes and stores keratin. Keratin is a fibrous protein that gives t hardness to the skin. It’s also what makes the hair and nails hard and what makes 49

skin relatively water resistant. The way it works is that the cells of the stratum basale migrate out and become keratinocytes, eventually becoming the stratum corneum, which actually consists of flat, dead keratinocytes. These will slough off, only to be replaced by cells coming from the next deepest layer. The stratum basale or stratum germinativum is the deepest layer of the epidermis. It is the cell layer that connects the epidermis to the basal lamina or basement membrane. Remember, the skin is a stratified squamous epithelial tissue. The basement membrane is made from collagen fibers that are intertwining and that have finger-like projections from the dermis extending up through it. These projections from the dermis that come through basement membrane are called “dermal papillae.” The dermal papillae are there to strengthen the connection between the deeper dermis in the skin to the more superficial epidermis. The greater the number of dermal papillae, the stronger is the connection between the dermis and the epidermis. Figure 25 shows dermal papillae extending up from the dermis to increase the connection to the epidermis:

The cells of the stratum basale are the most cuboid in shape of the epidermal cells; these are all precursor cells to the keratinocytes that make up the rest of the epidermis. These are highly mitotic cells, dividing constantly and then pushing more differentiated keratinocytes upward toward the skin surface. Within the basal cell layer is the Merkel cell, which is a sensory receptor cell that gives the skin its sense of touch. As might be imagined, there are more Merkel cells in the hands and feet, which tend to be more sensitive than other body parts. The other cell type seen in the stratum basale besides basal cells and Merkel cells is the melanocyte. This is the cell type that makes melanin under the influence of both genetics and exposure to UV radiation. These cells are protective of the rest of the skin by producing the melanin pigment that blocks UV radiation. Melanin is also what gives skin and hair its color. The stratum spinosum is the “spiny” layer of the skin. Each cell has protruding spines, which are where the processes of the cell that connect each cell to nearby cells via desmosomes. They strengthen the bond between cells of the epidermis. There are 8-10 layers of keratinocytes in this layer, which is made directly from the cells of the stratum basale. This layer also has Langerhans cells, which are dendritic cells that act to engulf pathogens and damaged cells. These Langerhans cells are part of the innate immune system in the skin. As mentioned, these cells are the first of the epidermal cells to make keratin. They also make and excrete a substance that is a glycolipid, which has the function of repelling water. Cells are continually added to the stratum spinosum by the stratum basale. The cells of the stratum spinosum then get pushed more superficially, where they become the cells of the stratum granulosum. The stratum granulosum is called as such because it has a grainy appearance under the microscope. The cells become flatter and have thicker cell membranes. There are 3-5 layers to this skin, which makes a great deal of keratin as well as a protein called keratohyalin. The keratohyalin is what makes the granules inside the cells. The proteins (keratin and keratohyalin) take up more mass than the cells themselves. The cells lose their nuclei and other organelles, leaving behind the cell membranes and proteinaceous material that will form the next layer up. This material is what goes into making hair and nails.

The stratum lucidum is the next layer up. This is the layer only seen on the thick skin of the hands and feet. These cells are flat and dead; they are packed with eleidin, which is a lipidladen clear protein that makes this layer relatively translucent. This protein gives this layer the ability to repel water. The stratum corneum is the most superficial layer in the epidermis. The keratinization of these cells is significant and there are 15-30 layers in this part of the epidermis. The cells are dead and dry; they prevent penetration of pathogens (microbes) and prevent the dehydration of the rest of the skin. The stratum granulosum or the stratum lucidum replace these cells, which are completely turned over after four weeks.

THE DERMIS The dermis is between the epidermis and the hypodermis. The dermis is vascularized, containing blood vessels, nerves, lymph vessels and accessory structures of the skin, such as the sweat glands and hair follicles. There are two layers to the dermis, made from the interconnection and weaving of collagen and elastin fibers—each of which is made by fibroblast cells. Figure 26 shows what the dermis looks like, including the structures within it:

The papillary layer of the dermis is made from loose areolar connective tissue, meaning that the elastin and collagen layers are structured in the form of loose mesh. This is the most superficial layer of the dermis and is the layer that forms the dermal papillae. There are fibroblasts within this layer as well as adipocytes, which are fat cells. Small blood cells that feed the epidermis abound in this layer. There are phagocytes that act to engulf pathogens that have somehow breached the upper layers. Lymphatic capillaries, nerve fibers, and Meissner corpuscles (touch receptors) are seen in this layer. The reticular layer is deeper and is much thicker than the papillary layer. It is made from dense and irregular connective tissue that support the overlying structures. There are sensory and sympathetic nerve fibers in this layer as well as many blood vessels. There are tightly woven elastin and collagen fibers that add to the tensile strength of the tissue. There are strands of collagen extending upward and downward in order to both keep the layers connect and bind water so the skin stays hydrated. Things like Retin-A and collagen injections act to restore the water to the skin and skin turgor, making it look younger and more refreshed.

THE HYPODERMIS The hypodermis or the “subcutaneous layer” is the layer beneath the epidermis. It connects the skin to the bones and muscles beneath it. It is considered to be closely connected to the skin but not technically part of it. This is highly vascularized and consists of adipose cells (adipocytes) and loose areolar connective tissue. It insulates the skin and cushions the underlying tissues. The adipocytes provide an energy reserve and protects the tissues beneath the skin from trauma. Exactly where the fat is stored depends on several hormones in the body, including estrogen, insulin, testosterone, leptin, and glucagon. Genetic factors also play a role in where the fat goes beneath the skin layers. Men build up fat on the arms, lower back, abdomen, and legs, while women collect fat on the breasts, thighs, buttocks, and hips. This fat is designed to “feed” the body in cases where there are no calories to be had. Unfortunately, this rarely happens in modern society so fat in the hypodermis builds up.

SKIN PIGMENTATION There are three pigments that make up the true color of skin: these are hemoglobin, carotene, and melanin. The melanin is created by melanocytes, which are in the stratum basale of the epidermis. There is an intracellular vesicle that stores melanocytes, called a melanosome. There are two different kinds of melanin: eumelanin (which is black and brown) and pheomelanin (which is red). As you can imagine, darker-skinned individuals make more melanin than lighter-skinned individuals. The melanin is actually stored in the keratinocytes that stimulate the melanocytes to make more melanin under the influence of UV (ultraviolet) radiation. As it builds up, the skin becomes darker. This protects the skin from suffering from DNA damage by exposure to more UV radiation. It also prevents folic acid breakdown. Too much melanin will interfere with vitamin D production. It takes ten days after sun exposure to have a peak in melanin production. Melanosomes get destroyed by lysosomes and the keratinocytes get sloughed off so tans do not last. Tanning too much will wrinkle the skin by destroying the cellular infrastructure of the skin. In severe cases, the UV exposure seen in tanning beds and sun exposure will cause enough DNA damage to cause skin cancer. Freckles are accumulations of melanocytes that occur in certain areas of the skin. Moles are even bigger accumulations of melanocytes. It is from moles that melanocytic cancers called melanomas arise.

ACCESSORY SKIN STRUCTURES The accessory skin structures include the sebaceous glands, sweat glands, hair, and nails. These are embryologically from the epidermis but are located in area as deep as the hypodermis. Hair gets its specific color from the melanin pigment and made from dead keratinized cells. Nails are similarly made from these types of cells and act as protection for the fingertips and the tips of the toes. The sweat glands produce sweat, while the sebaceous glands produce oil called sebum.

THE HAIR Hair grows out of the epidermis as a keratinized filament. The origin of the hair is the hair follicle, which is located in the dermis. The hair shaft is that portion of the hair not within the follicle. Most of the shaft is visible above the surface of the skin. The root of the hair is within the follicle, ending in the hair bulb. The hair matrix involves those basal cells that continually divide in order to make the hair grow. There is a connective tissue-derived hair papilla that is enclosed within the hair bulb and that contains both nerve endings and capillaries in the dermal layer. The basal cells that make up the hair shaft divide and push cells outward in the hair root and up into the hair shaft. This causes the hair to grow. There is an inner medulla and an outer cortex, which is made from compressed, keratinized cells. The cortex is covered by the cuticle, which is a hard-packed exterior of dead keratinized cells. Figure 27 shows the basic anatomy of a hair bulb in the hair follicle:

The texture of the hair (whether it is curly or straight) is determined by the appearance and structure of the cortex and the medulla. As new cells are placed into the hair bulb, the shaft is pushed upward, causing hair to grow. Keratin is added to these cells so that they are fully keratinized by the time they reach the surface of the skin. This makes the visible hair completely dead and made only of keratin. When hair is cut or shaved, only the visible portion is removed and the hair follicle remains intact and continually grows hair. Only with electrolysis and pulling the hair out can the bulb of the hair be destroyed. In the hair follicle, there are three concentric layers of cells. The internal root sheath cells surround the root of the hair that is growing. These cells extend to the level of the shaft of the hair and come from the basal cells of the hair matrix. The external root sheath is an extension of the epidermis and encloses the hair root. It is made from basal cells near the base of the hair root. The glassy matrix is the outer connective tissue sheath that covers the hair root, connecting it to the dermal tissue. Hair provides protection, sensory input, communication, and thermoregulation of the body. Hair in the ears, nose, and around the eyes (the eyelashes) defends the body through trapping of dust particles, microbes, and allergens. The eyebrow hair protects the eyes by trapping sweat into them. The hair follicle is highly sensitized with sensory receptors so the hair is important to sensation. Hair is particularly sensitive to air movement disturbances and the invasion of insects near the skin. Each hair is connected to the arrector pili muscle—a smooth muscle that contracts by input from the sympathetic nervous system, causing the hair to “stand erect.” This adds to thermoregulation by trapping hair that can be warmed by the body. Goose bumps are the erection of hair in response to cold exposure and are seen in other mammals as well. There are three phases to hair growth. The anagen phase is when there is rapid division of hair at the root so that the hair can grow out of the skin. This phase lasts the longest at 2-7 years. It is followed by the catagen phase, which is the shortest phase of hair growth, lasting just 2-3 weeks. It is a transition phase that marks the end of active growth. The telogen phase is last, lasting just 2-4 months, during which no new growth occurs. Then another anagen phase

occurs. A new hair follicle is made and the old hair follicle falls out, repeating the cycle. About 50 hairs are lost and replaced every day but this can increase because of hormonal or dietary changes. Aging and certain hormones can influence the hair cycles and can cause increased hair loss. Figure 28 shows the different stages of hair growth.

In the hair papilla, there are melanocytes that give hair its color. This is genetically determined. The amount of melanin in the hair shaft declines with age, causing the hair to look white or gray.

THE NAILS The nail consists of a nail bed that is actually a specialized epidermal structure seen only on the tips of the toes and fingers. The nail body is formed upon the nail bed and protect the most distal parts of the body, which receive the most mechanical stress. The nail body is also helpful in picking up small objects with the fingers; it is made from packed keratinocytes that are dead. The source of the nail body is the nail root, which has its own matrix of proliferating cells originating from the stratum basale. The nails grow continually from this matrix. The nail fold or nail groove is on the sides of the nail and help anchor it. The proximal end of the nail body is the nail cuticle. The nail cuticle is also known as the eponychium. The lunula is the pale part at the base of the nail; it is pale because the epidermis is thicker there. The hyponychium is the most distally-connected part of the nail bed—made from a thick stratum corneum layer. Figure 29 shows what the anatomy of the nail looks like:

SWEAT GLANDS Sweat glands are also referred to as sudoriferous glands. They make sweat, which cools the body. They are actually epidermal projections that extend into the dermis. These fall under the classification of “merocrine glands” because the secretions actually happen via exocytosis through a duct. Figure 30 shows what a sweat gland looks like:

There are two main types of sweat glands: eccrine and apocrine sweat glands. The eccrine sweat gland produces hypotonic sweat fluid used for thermoregulation. They are found all over the body but especially on the palms of the hands, the bottoms of the feet, and the forehead. They lie deep in the dermis and have a duct that leads to the surface of the skin. The sweat is released via exocytosis and is made mainly of water, but also contains metabolic waste, salt, antibodies, and dermcidin (an antimicrobial peptide). Apocrine sweat glands are affiliated with hair follicles, seen mainly in the genital and armpit area. These are deeper in the epidermis and empty their sweat into the hair follicle. It contains water and salts as well as organic compounds that thicken sweat. It is the decomposition of these compounds by bacteria that causes the smell of these areas. This is part of the human pheromone response and the ducts that are blocked by aluminum-based antiperspirants.

SEBACEOUS GLANDS Sebaceous glands are oil glands found throughout the skin of the body. The oil helps to keep the skin and hair waterproofed and lubricated. Most sebaceous glands are linked to hair follicles. There is a mixture of lipids called sebum that is secreted by these glands. The fatty acids in these secretions have antibacterial properties and keep the skin from losing water in low-humidity environments. Sebaceous glands are inactive for the most part in childhood and become activated around the time of puberty.

FUNCTIONS OF THE SKIN The skin and its accessory structures perform many important functions. These include the protection of the body from the hazards of the environment, the prevention of dehydration, protection against pathogens, thermoregulation and electrolyte balance, and vitamin D synthesis. The hypodermis acts to store fat, which cushions and insulates the body. The skin protects the body from things like excessive exposure to water, UV radiation, and cold. It protects the body from water loss due to the presence of glycolipids and keratin in the stratum corneum. Any abrasive action from the environment comes in contact with the skin

first, which protects the rest of the body. The dermcidin in the sweat is antibacterial so that the growth of pathogens is kept at bay. The skin also has a significant sensory function. It’s mainly the hairs that have sensory activity because they can sense environmental changes. The sensory impulse is transmitted to the brain, which then acts on the motor system so the individual will respond by, for example, flicking away an insect or piece of debris. There are sensory nerve structures in the skin itself that detect things like pain, temperature, and light touch. The receptors are seen in greater numbers on the fingertips, making them more sensitive to light touch. The Meissner corpuscles are the detectors of light touch, while the Pacinian corpuscles detect vibration. The Merkel cells in the stratum basale are also touch receptors. Each hair follicle has a sensory receptor attached to it and there are pain and temperature receptors that are found in the skin for maximum sensation. The skin is also responsible for thermoregulation. It is highly connected to the sympathetic nervous system—the part of the nervous system that monitors body temperature and initiates specific motor responses in return. The sweat glands will secrete water and salt in order to cool the body in warm temperatures, with 0.5 liters of sweat secreted every day even when not noticeably sweaty. In hot environments or with heavy exercise, up to 1.5 liters of fluid can be secreted every hour. It’s the evaporation of that sweat that dissipates body heat. Besides sweating, the arterioles in the skin will dilate to dissipate heat in response to hot temperatures, which is why the skin turns red with exercise. These same arterioles will constrict in cold temperatures in order to decrease heat loss. If there is excessive cold, the arterioles in the skin constrict drastically in the extremities to preserve core body heat. This leads to frostbite. As a person gets older, the skin will change. There will be decreased mitosis in the stratum basale, which leads to thinning of the epidermis. The dermis will regenerate more slowly so there will be decreased elasticity of the skin as well as decreased resilience. There is a reduction and redistribution of fat stores in the hypodermis, which further leads to sagging and thinning of the skin.

There will be decreased activity of the accessory structures as a person gets older, so the skin will have thinner nails and hair, decreased sweat, and decreased sebum. The decreased sweating leads to heat intolerance. The skin will become paler because of decreased melanocytic activity. Dendritic cells decrease in activity so the immune system is less active in the skin. Collagen and elastin levels drop so there is wrinkling and the skin becomes drier. The epidermis of the skin is what synthesizes vitamin D when exposed to the sun’s UV radiation. Vitamin D3 is made from a cholesterol derivative housed in the skin. This vitamin D3 (cholecalciferol) goes to the liver to make calcidiol, which goes to the kidneys to make calcitriol—the active form of vitamin D. A lack of vitamin D leads to rickets in severe cases (in children only). Older patients with vitamin D deficiency will have an increased risk of osteomalacia.

DISORDERS OF THE SKIN SKIN COLORATION DISEASES There are a number of skin coloration disorders—most of which are relatively benign. Albinism is a genetic condition that either partially or completely reduces the coloration of the skin, hair, and eyes. There are several types of albinism but the main defect is the inability to make melanin. The skin is very pale and unprotected by melanin from UV radiation. There is a high risk of both sunburn and skin cancer in individuals with this disorder. Light sensitivity is also common because the retina is not pigmented. Other individuals can have patchy loss of melanin, affecting only some of the skin. For example, vitiligo involves areas of the skin affected by de-pigmentation and normal areas of skin. This is secondary to an autoimmune disease that affects the melanocytes. Only the de-pigmented skin is prone particularly to skin cancer. Figure 31 describes what vitiligo looks like:

Skin can also be yellowed by liver disease—a condition called jaundice. The pigment bilirubin (which is yellow) is not able to be processed by the liver so that there is an accumulation of the molecule in all areas of the body; it is most noticeable in the whites of the eyes and in the skin. Other color-related skin conditions include skin darkening from tumors of the pituitary gland, which makes melanocyte-stimulating hormone (MSH) that darkens the skin. Patients with Addison’s disease have an excess of ACTH (adrenocorticotropic hormone) that mimics MSH and causes activation of the melanocytes. A lack of oxygen can be reflected in the skin. Initially, the skin will whiten from a lack of oxygenated hemoglobin, which is the red-pigmented molecule that gives skin its coloration. If this condition becomes prolonged, the skin will develop cyanosis—a bluish discoloration, from an excess of darker red-colored deoxygenated hemoglobin. Some babies will be born with heart defects that cause mixing of oxygenated and deoxygenated blood, so they will be born with cyanosis.

SKIN CANCER Skin cancer, like other cancers, occurs when cells of the body divide uncontrollably, taking over normal tissues. About 20 percent of individuals will have skin cancer at some time in their lives. This is an increase over the past several decades because of increases in UV radiation exposure from ozone depletion. The main cause of skin cancer is DNA damage from UV radiation

exposure. Melanin will be protective from this type of damage but it will not be completely protective. Less commonly, skin cancer will develop on non-sunexposed areas of the skin. The most common type of skin cancer is basal cell carcinoma. It comes from the cells of the stratum basale in the epidermis. It is mainly seen in skin areas that are chronically exposed to the sun. Although it is most commonly secondary to sun exposure, things like arsenic and other types of radiation will cause this type of cancer. In addition, skin wounds can predispose areas of the skin to this type of cancer. Basal cell cancer does not metastasize (spread to other body areas) but it can damage the tissue locally. Squamous cell carcinoma of the skin originates in the keratinocytes of the stratum spinosum layer of the epidermis. These will show up on the ears, scalp, and hands; it represents the second most common type of skin cancer. It tends to be more aggressive than basal cell cancer and has the propensity to metastasize if not treated by removing the cancer. Melanoma is a less common type of skin cancer that is derived from an uncontrolled growth of the melanocytes. Melanomas come often from moles and is the most fatal of all the common skin cancers. It has a tendency to metastasize and can be hard to detect before it has already spread to other organs of the body. Melanomas look like moles but will be more irregular in shape, have unusual and variegated coloring, a raised surface, and an evolving appearance. They also tend to be larger than normal moles and will enlarge with time. They are treated with wide surgical excision and drugs that activate the immune system to fight the melanoma.

BENIGN SKIN CONDITIONS Most skin conditions are benign and are extremely common. The different skin disorders that are seen in adults, teens, and children include psoriasis, eczema, acne, seborrheic dermatitis (dandruff), impetigo (a bacterial infection affecting children), scabies (a parasitic infection), hives (an immune reaction of the skin), warts (a viral infection), and cold sores (a viral infection of the skin). Eczema is a relatively common allergic reaction seen as patchy areas of dry and itchy skin that is often so itchy the skin bleeds. It is believed to be a skin reaction to an environmental allergy,

such as dust mites and nickel. Patients tend to get better after using moisturizers, topical corticosteroid creams, and immunosuppressant drugs. Acne is also common and affects mainly adolescents. It is seen mainly on areas of the skin where there are a lot of sebaceous glands and is related to androgenic hormones that begin to be prominent in puberty. Androgens are known to increase sebaceous gland secretion, leading to a white plug of material in the skin pore. When oxidized by air, the sebum becomes black, forming a blackhead. True acne occurs when acne-causing bacteria infect the skin, leading to focal redness and possible small abscess formation. Acne scarring can occur as the infection heals. The skin is particularly prone to injuries as it protects the rest of the body. Wounds can include abrasions, lacerations, and burns. As the skin is injured, a blood clot stops the flow of blood. Then, fibroblasts come to the area and clean out debris and dead tissue. Collagen is deposited, making what’s known as “granulation tissue.” Capillaries will grow into the area and pave the way for immune cells to come in to prevent infection. Then the stratum basale can rebuild a scar to cover the epidermis, leading to a scar. Burns happen to the skin as a result of severe heat damage, radiation exposure, electrical injury, and certain chemical exposures. The cells die off and there is significant loss of fluid in the burned area. Severe burns can result in electrolyte imbalances, kidney failure, infection, and possible death. IV fluids may be necessary to avoid dehydration from fluid losses. The lack of skin protection from pathogens can lead to a great risk of infection. There are several degrees or severities of burns. First-degree burns are the mildest type of burn, affecting just the epidermis without blistering. Second-degree burns involve the epidermis and part of the dermis. These will lead to blistering of the skin. Third-degree burns affect both the epidermis and the dermis. The skin is leathery and black, brown, or white. It leads to scarring and will not be painful because the nerve endings have been burned. The most severe burn is the fourth-degree burn, which affects underlying tissues, including possibly muscle and bone. Skin grafting may be necessary for third-degree and fourth-degree burns.

Many skin wounds will lead to scar tissue. A scar forms from collagen that is irregularly deposited in place of an injured area. Fibroblasts go to the affected area and make a basketweaved pattern from interlocking collagen fibers that do not recreate the original appearance of the skin. The scar tissue is highly fibrous when compared to regular skin and doesn’t contain the normal accessory structures seen in normal skin (no hair follicles, sweat glands, or sebaceous glands). An overproduction of scar tissue leads to a raised scar known as a keloid. Calluses form on certain parts of the skin, particularly on the hands and feet, from extended wear and abrasion on the skin. The basal cells of the stratum basale are triggered to divide to an excessive degree, leading to an increased thickness of the epidermis. The goal of a callus is to prevent further damage to skin by increasing the cushioning of underlying tissues by having a thick and keratinized epidermis. Corns represent a specialized form of callus that comes from abrasion of the skin over a period of time. The motion that causes a corn is elliptical in nature so that the callous forms in a circular pattern on the feet.

KEY TAKEAWAYS •

There are two main layers to skin, the epidermis and the dermis, with the hypodermis being the subcutaneous layer beneath these two layers.

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There are 4-5 layers to the epidermis, depending on whether it is thick or thin skin.

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Accessory structures of the skin are seen mainly in the dermis.

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The skin has many functions, such as thermoregulation, mechanical protection, and pathogenic infection prevention.

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There are benign and cancerous skin diseases, with skin cancer affecting 20 percent of people at some time in their lives.

QUIZ 1. Which is the most superficial layer of the skin? a. Stratum basale b. Stratum lucidum c. Stratum spinosum d. Stratum corneum Answer: d. The stratum corneum is the most superficial layer of the skin in all of the integumentary system? 2.

Which layer of the skin is only seen in what’s known as “thick skin” on the palms and soles? a. Stratum corneum b. Stratum spinosum c. Stratum lucidum d. Stratum basale Answer: c. The stratum lucidum is only seen in thick skin as the fifth layer of this type of skin.

What cell type is not seen in the stratum basale of the skin? a. Merkel cell b. Keratinocyte c. Melanocyte d. Basal cell Answer: b. Each of these cell types is seen in the stratum basale of the epidermis except for keratinocytes, which are seen in only the other layers of the epidermis.

Which protein gives skin its “hardness”? a. Eleidin 67

b. Keratohyalin c. Keratin d. Collagen Answer: c. Keratin not only makes skin “hard”, it accounts for the hardness of the nails and hair. 5.

Which layer is not technically a part of the skin? a. Epidermal layer b. Reticular layer c. Hypodermal layer d. Papillary layer Answer: c. The hypodermal layer or hypodermis is a layer beneath the dermis that is not directly a part of the skin. It is the subcutaneous layer that provides a connection between the dermis and underlying structures of the body.

Which protein protects the skin from UV damage? a. Keratin b. Hemoglobin c. Melanin d. Collagen Answer: c. It is melanin—a dark-skinned pigment—that protects the skin from UV damage by blocking UV rays from getting to deeper structures below the epidermis.

Which structure is the most external in the hair follicle? a. Hair root b. Internal root sheath c. External root sheath d. Glassy matrix

Answer: d. The glassy matrix is the outer layer of the hair follicle and connects the follicle to the dermis outside of the hair follicle. 8.

Which hair growth phase occurs when the new hair follicle first develops? e. Late anagen f. Early anagen g. Catagen h. Telogen Answer: b. The early anagen phase is the beginning of the next hair cycle and starts the formation of a new hair follicle.

Which is not a characteristic of the apocrine sweat gland? a. It lies deeper than the eccrine glands b. It secretes pheromones c. It is associated with a hair follicle d. It is the main gland responsible for thermoregulation in the body Answer: d. In fact, each of these is true of the apocrine gland except it is the eccrine gland that is the main sweat gland involved in thermoregulation.

10.

In the skin, there are many receptors. What do the Pacinian corpuscles detect? a. Pain b. Vibration c. Light touch d. Temperature Answer: b. The Pacinian corpuscles in the skin specifically detect vibration. There are other sensory receptors in the skin that detect the other basic skin sensations.

CHAPTER FOUR: SKELETAL SYSTEM This chapter starts with a discussion of the anatomy and physiology of bone cells and tissue. Then the axial skeleton (the skull, spine, and ribcage) is covered in detail as well as the appendicular skeleton (mainly the extremities). The functions of joints and ligaments are discussed as they are important aspects of the skeletal system.

BONE STRUCTURE AND FUNCTION Bone is also referred to as osseous tissue. It is considered a connective tissue and forms the bulk of the human skeleton, the function of which is to protect and support the body’s structures, move the body, make blood cells, store minerals, and store fat. The entire skeletal system is composed of bones, cartilage, and supporting ligaments. It’s through its connection with muscles that the skeleton provides body movement. The bones are the levers of the body, while the joints are the fulcrums. It takes the connection of the muscles and their contraction to allow for movement. The bones have several functions that aren’t immediately visible. The bone matrix has the ability to store and act as a reservoir for several major minerals, particularly phosphorus and calcium. It is also a storage milieu for fat cells and its marrow makes red and white blood cells. There are two types of bone marrow: red and yellow marrow. Red marrow is for hematopoiesis (blood cell production), while the yellow marrow is for the storage of fat. We will talk more on this later.

TYPES OF BONES There are 206 bones in the human skeleton, which are made from five different types. The different types are based on the shape of the bone, which is highly associated with their function. Let’s look at the different categories of bones:

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Long bones—these are the typical bones you think of as they are long and cylindrical in nature. Long bones include the humerus, ulna, radius, tibia, femur, fibula, and digit bones. They act as true levers that move when muscles contract around them.

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Short bones—these are more cuboidal in shape and include both the carpals and the tarsal bones. They provide limited motion, stability, and support.

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Flat bones—these are thin, curved bones, including the cranial bones, scapulae, ribs, and sternum. They are protective of internal organs and attach certain muscles.

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Irregular bones—these have an unusual shape that depends on their function. The facial bones and vertebrae are considered irregular bones.

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Sesamoid bones—these are small, round bones that form inside tendons. They protect the tendons and are generally unnamed, except for the patella. Otherwise, the number of sesamoid bones varies with the person. The purpose is to protect tendons from compressive forces.

BONE ANATOMY The long bone has the best gross anatomy for understanding what the anatomy of the bone. There are two parts to most bones: the epiphysis and the diaphysis. The diaphysis is the shaft of the bone from one end to the other. Inside the bone is the medullary cavity, which is filled with yellow marrow. It has dense walls made from compact bone. Figure 32 describes in picture form what the bone looks like:

At the end of each long bone is a wider area known as the epiphysis. This is filled with spongy bone and red marrow. Each epiphysis meets the diaphysis at the metaphysis, which is a narrower area that consists of the epiphyseal plate, which is the growth plate of the bone. When the person stops growing, the epiphyseal plate becomes ossified and defined as the epiphyseal line. There is a membranous lining called the endosteum inside the bone in the medullary cavity. This is where bone repair, remodeling, and bone growth occur. The outer membrane of bone is called the periosteum, which contains the blood vessels, lymph vessels, and nerves that supply the compact bone. Tendons and ligaments attach to bones at the periosteum. It covers the entirety of bone except where the epiphyses for joints; this is where the articular cartilage covers bone instead. Flat bones are slightly different from long bones. They have two layers of compact bone that sandwiches a spongy layer called the diploe. The inner layer can protect the internal structure, such as the brain in the cranial bones, even if the outer layer gets fractured.

BONY MARKINGS There are many different markings on bone, of which there are three types: •

Articulations—also referred to as joints, where two bones meet to facilitate movement.

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Projections—these will stick out of a bone and is often where tendons and ligaments attach.

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Holes—this is a groove or opening in the bone where nerves and blood vessels enter the bone.

Types of articulations include the following: •

Head—such as the head of the femur, in which there is a prominent rounded surface at one end

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Facet—this is a flat end of the bone, such as the facet joint of a vertebral bone

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Condyle—this is a rounded projection, such as the occipital condyles

Types of projections include the following: •

Protuberance—a protruding projection, such as the chin

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Process—a prominence that sticks out of the bone, such as the transverse process of a vertebra

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Spine—this is a sharp process, such as the ischial spine or the spine of the scapulae

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Tubercle—this is a small, rounded process, such as the tibial tubercle (a tendon insertion spot)

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Tuberosity—a rough projection, such as the deltoid tuberosity (a tendon insertion spot)

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Line—this is a ridge that is slightly elongated and elevated (such as the temporal lines of the parietal bones)

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Crest—this is a ridge of bone, such as the iliac crest

There are several kinds of holes in bones, including the following: •

Fossa—an elongated basin in a bone, such as the mandibular fossa

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Fovea—a small pit in the bone, such as the fovea capitis (on the femur head)

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Sulcus—this is a groove in the bone, such as the sigmoid sulcus in the temporal bone

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Canal—a passage within the bone, such as the auditory canal

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Fissure—this is a slit through the bone, such as the auricular fissure

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Foramen—this is a hole through the bone, such as the foramen magnum in the skull

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Meatus—this is an opening into a canal including the external auditory meatus

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Sinus—an air-filled space within the bone, such as the ethmoid sinus

BONY TISSUE Bone contains several types of cells that are suspended in collagen fibers that provide the proteinaceous surface for inorganic salt crystals to stick to. The calcification of bone on collagen fibers gives rise to hydroxyapatite, which is both hard and slightly flexible. The cells themselves make of a small amount of the volume and mass of bone, consisting of the following: •

Osteoblasts—these are cells that produce new bone, including the periosteal and endosteal membranes. These are non-dividing cells that secrete collagen matrix as well as calcium salts. The osteoblast becomes trapped within the bone matrix and turns into an osteocyte.

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Osteocytes—the osteocyte is the major cell in mature bone, formed from osteoblasts. These cells are surrounded by bony tissue in a space called a lacuna. They secrete enzymes that maintain minerals within the bone. These are non-dividing cells. There are channels called canaliculi that connect osteocytes with one another to provide cellcell communication.

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Osteogenic cells—these are undifferentiated cells that are capable of mitosis and are the only bone cells that divide. They are found deep to the periosteum and in the marrow, where they develop into osteoblasts.

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Osteoclast—the osteoclast is the cell that breaks down bone. They originate from macrophages and monocytes and not from osteogenic cells. They break down bone and are essentially the opposite of osteoblasts. Bone is reshaped by the action of these bone cells and osteoblasts.

Figure 33 illustrates what the different bone cell types look like:

SPONGY BONE VERSUS COMPACT BONE There are differences between the two main types of bone: spongy and compact bone. Compact bone is extremely dense and supportive of the skeleton, while spongy or cancellous bone is filled with open spaces so that the bone is not brittle and can withstand compression. Compact bone can be found in the bony diaphysis and beneath the periosteum. The compact bone must be innervated somehow. There is a central canal called a Haversian canal that contains the blood vessels, lymphatic vessels, and nerves that go to the structural unit of this type of bone, called the osteon. The osteon is made from concentric lamellae, which are calcified matrices that give the osteon its structure. There are perforating canals that branch off the central canal called Volkmann’s canals, which supply the endosteum and periosteum. Nutrients get passed to osteocytes by means of the canaliculi. The spongy or cancellous bone contains loosely packed osteocytes. There are trabeculae, which are matrix spikes that form a lattice in which the lacunae are found. The trabeculae are not randomly placed but fall along lines that provide strength to stressed bone, making the bone able to withstand stressors yet decreasing the density of bone. Spongy bone and the bony medulla receive their blood supply through nutrient foramina that pass through compact bone. The blood passes through the marrow spaces and is picked up by veins that exit the bone through the foramina (which contain both arteries and veins). Nerves also pass through these foramina. The nerves give bone the ability to sense deep pain.

BONE GROWTH Bones grow in length through the action of the epiphyseal plate. This is a layer of hyaline cartilage that ossifies in young people along the diaphyseal side. On the epiphyseal side of the plate, new cartilage is formed. This results in a lengthening of the bone. The reserve zone contains chondrocytes within the matrix that secure the epiphyseal plate to the bony tissue of the epiphysis. Figure 34 of the manual shows a micrograph of what the epiphyseal plate looks like:

The proliferative zone in the epiphyseal plate is toward the diaphysis, containing stacks of chondrocytes that makes new chondrocytes all the time. These chondrocytes mature in the “zone of maturation and hypertrophy” that mature and are pushed toward the diaphyseal end of the plate. These are ultimately pushed through the zone of calcified matrix, which contains dead cells surrounded by calcium deposits. This connects the epiphyseal plate to the diaphysis. After bone grows and is finished, the chondrocytes do not proliferate and bone replaces the cartilage, making the epiphyseal line. Bones also increase in diameter through the action of osteoclasts and osteoblasts. The osteoclasts break down bone in the medullary cavity, while the osteoblasts produce new bone beneath the periosteum. The end result is an increase in the diameter of the bone through the process of modeling. Remodeling occurs in the same way as modeling after a fracture or when the bone needs to change shape in adulthood (because of exercise or injury). About 5-10 percent of adult bone is remodeled every year to be replaced by new bone.

BONES AND NUTRITION There are certain nutrients that are particularly associated with bone health. Because calcium is so important to bone health, so is vitamin D. Vitamin D is necessary for the absorption of calcium in the small intestine. It also plays a role in the remodeling of bone, although this isn’t understood. Calcium can be found in milk and dairy products, leafy green vegetables, broccoli, nuts, seeds, beans, and salmon. Vitamin D is in fortified foods and produced by the body after the exposure to sunlight. Many people are deficient in vitamin D, necessitating supplementation. Other nutrients important in the formation of bone include vitamin K. This adds synergistically to vitamin D, creating bone growth. Vitamin K can be found in leafy green vegetables. Magnesium and fluoride are also vital to bone health. About 60 percent of all magnesium in the body is stored in bone. Fluoride is especially important in tooth health; it forms fluorapatite out of hydroxyapatite crystals and helps strengthen bones and teeth by increasing their density. Omega-3 fatty acids form strong bones by enhancing the production of new bone.

HORMONES AFFECTING BONE The endocrine system makes and secretes hormones that help the skeletal system. There are hormones that influence osteoblasts and hormones that influence osteoclasts. One example is growth hormone (GH), which is secreted by the anterior pituitary gland. It stimulates the proliferation of the chondrocytes, increasing the length of long bones. It also increases the mineralization of bones, stimulating the osteoblast activity. This enhances bone density. In addition, thyroxine secreted by the thyroid gland, will promote osteoblast activity and the synthesis of the bony matrix. Sex hormones at puberty (estrogen and testosterone) promote osteoblast activity in order to lengthen the bone during adolescence. Calcitriol, which is the active form of vitamin D, is able to stimulate calcium and phosphate absorption in the GI tract. Parathyroid hormone activates the osteoclasts and increases their activity. This releases calcium from the bones in order to increase the calcium concentration in the blood. It also

helps the kidneys hold onto calcium so that there is more calcium in the blood. Finally, it stimulates vitamin D synthesis so that the calcium can be better absorbed by the GI tract. Calcitonin is made by the thyroid gland and inhibits osteoclast activity, stimulating the uptake of calcium by the bones. This is opposite to the action of PTH so that the calcium ion concentration in the blood is decreased. These hormones are generally not secreted at the same time but together manage the concentration of calcium in the blood.

AXIAL SKELETON There are two divisions to the skeleton: the axial and the appendicular skeleton. The axial skeleton forms the central, upright axis of the body, including the bones of the head, the neck and back bones (vertebrae), and the ribcage (including the sternum). This part of the skeleton keeps the brain, spinal cord, lungs, and heart protected. There are numerous muscular attachments to these bones, which allow for facial movements, the action of the neck and back, and breathing movements. There are 80 bones in the axial skeleton, of which 22 are found in the skull. The vertebral column consists of 24 bones called vertebrae (plus the sacral bone and the coccyx). The thorax has 12 pairs of ribs plus the sternum. Figure 35 illustrates what the axial skeleton looks like:

THE CRANIUM The cranium or skull is the main skeletal structure of the head. It is divided into the brain case or cranial vault and the facial bones. Of all the 22 bones of the skull, 21 are immobile and fused together. Only the mandible or lower jaw is separate and mobile. Figure 36 shows what the anterior view of the cranium and facial bones looks like:

From the anterior view, the skull can be seen as mainly showing the facial bones. The upper and lower jaw is formed as the maxilla and mandible, respectively, which houses the teeth. The orbit is the eye socket that houses the eyeball and the muscles that move it. On the upper side of the eye socket is the supraorbital margin, which contains a small opening called the supraorbital foramen. This is where the nerve that serves the sensation of the forehead comes 80

through. There is an infraorbital foramen below the eye that allows the sensory nerve to the face to pass. Inside the nose is the nasal cavity, divided by the nasal septum, which is formed by part of the ethmoid and vomer bone. The lateral wall of the nasal cavity has two bony plates, called the inferior nasal concha and the middle nasal concha. The superior nasal concha is much smaller and is a part of the ethmoid bone. The lateral view of the skull involves primarily the cranial vault and the sides of the jaw. The zygomatic arch is the bony arch that creates the cheek and is often referred to as the “cheekbone.” It is formed by the temporal process of the zygomatic bone and the zygomatic process of the temporal bone. This forms the arch. Its function is to attach bones that cause the mandible to chew. The temporal fossa is located above this arch and the infratemporal fossa is located below this arch. These also have muscle attachments that cause the mandible to chew. The brain case or cranial area is the part that protects the brain. The calvaria is called the skullcap and forms the rounded top of the brain case. The floor of this case is the floor of the skull. Inside the skull are three spaces, the anterior, the middle and the posterior cranial fossa. Figure 37 shows the brain case bones:

There are eight bones of the brain case, including the following: •

Parietal bone—this is the upper lateral side of the skull. There are two of them that join together at the top of the skull.

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Temporal bone—this forms the lower lateral side of the skull. It contains the ear canal and a large prominence called the mastoid process, which serves as a muscle attachment site.

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Frontal bone—this is the single bone that forms the forehead. The midline is a slight depression called the glabella. It forms the supraorbital margin of the eye and brow ridges. It also forms the floor of the anterior cranial cavity interiorly.

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Occipital bone—this is a single bone in the back of the brain case, forming the base of the cranial cavity. It has protuberances that attach muscles that move the neck, in particular the superior nuchal line. The foramen magnum that the spinal cord passes through is a hole within this bone.

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Sphenoid bone—this is a single bone in the middle of the skull and is attached with nearly every other bone of the skull, forming the base of the central skull. It contains the sella turcica that houses the pituitary gland. Figure 38 illustrates the brain case and the sphenoid bone:

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The ethmoid bone is midline and forms the roof and sides of the upper nasal cavity, contributing to the medial wall of the orbital cavity and part of the anterior cranial cavity. There is a specialized plate called the cribriform plate in this bone that helps olfactory nerve fibers reach the nose so we can smell.

FACIAL BONES The facial bones are all attached, except for the mandible. These bones form the upper and lower jaw, the nasal septum, the nasal cavity, and the orbit. There are fourteen bones in the face, most of which are paired (except for the mandible and vomer bones). The ethmoid bone is a cranial bone but it participates in making the face as well. Bones of the face include the following: •

Maxillary bone—this is also called the maxilla and forms the upper jaw, the medial orbit, the hard palate, and the lateral base of the nose. It contains the upper teeth. There are 83

alveoli (singular is alveolus), which are the attachments to the teeth. The hard palate is the bony plate at the roof of the mouth. •

Palatine bone—this is an irregular bone that mainly forms a horizontal plate that makes the posterior one-fourth of the hard palate, making it seen best on an inferior view of the skull.

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Zygomatic bone—this is what makes the cheekbone via the zygomatic arch. It also forms the lateral wall of the orbit.

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Nasal bone—these two bones join together to make the bridge of the nose (where eyeglasses sit). They support the cartilage that forms the lateral walls of the nose and damaged when one breaks one’s nose.

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Lacrimal bone—this is a small bone that forms the antero-medial wall of the orbit. It has a small lacrimal fossa and the nasolacrimal canal, through which the tear ducts pass.

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Vomer bone—this is an unpaired bone that forms the posterior and inferior part of the nasal septum.

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Mandible—this forms the lower jaw and is the only moveable bone of the skull. It is a paired bone at birth but later fuses to form a U-shaped structure. It houses the lower teeth.

The orbit or eye socket houses the eyeball and the muscles that move the eye and open the upper lid. They lateral wall diverges at a 45-degree angle from midline to allow for peripheral vision to the sides of the head. There are seven skull bones that form the walls of each orbit. The back of the orbit has an opening called the optic canal, which allows for passage of the optic nerve from the back of the eye to the brain. The nasal septum consists of both cartilage and bone. It is formed by parts of the ethmoid and vomer bone. The anterior nasal septum is made by septal cartilage that fills in the gap between the two bony aspects of this septum. The superior, middle, and inferior nasal conchae extend into the nasal cavity on the lateral walls of the cavity. They trap mucus and warm air before entering the back of the nasal cavity.

INSIDE THE SKULL The floor of the cranial cavity, as mentioned, is divided into three spaces called cranial fossae. They increase in depth from the anterior to posterior parts of the brain case. Each has a boundary anteriorly and posteriorly and is divided at the midline by a major opening or bony structure. The anterior cranial fossa is the shallowest and overlies the orbits. It contains the frontal lobes of the brain. Behind it is the deeper middle cranial fossa, which is butterfly-shaped. There are several openings in this fossa for the cranial nerves and several blood vessels to pass. The posterior cranial fossa is the deepest and houses the cerebellum. It is divided in the middle by the large foramen magnum, through which passes the spinal cord. There are several sinuses inside the skull bones. These are hollow, air-filled spaces located within certain bones of the skull. All of the sinuses empty into the nasal passages. They are lined with nasal mucosal tissue. Their function is to reduce bone mass and lighten the skull, adding resonance to the voice. They also produce mucus when one has a cold. Figure 39 shows the sinuses and their entry into the nasal cavity:

The different sinuses are the frontal sinus (above the eyebrows), the maxillary sinuses (overlying the cheeks in the maxillary bone), the sphenoid sinus (which is a single, midline sinus), and the ethmoid air cells.

THE HYOID BONE This is the largest independent bone in the body and does not come in contact with any other bone. It is located in the front of the neck and is not a part of the skull. It is U-shaped and has, as its function, the attachment of the base of the tongue, the larynx (below), and the pharynx (posteriorly). Figure 40 is a picture of the hyoid bone:

VERTEBRAL COLUMN The vertebral column or spinal column is a sequence of vertebrae, which are separated from one another by an intervertebral disc. These stack up to make the entire vertebral column. It supports the trunk of the body and protects the spinal cord. There are 24 vertebrae plus the

sacrum and the coccyx. There are seven cervical vertebrae, 12 thoracic vertebrae, and five lumbar vertebrae. There are four curvatures to the vertebral column—designed to increase the strength, shockabsorbing, and flexibility of the spine. There are primary curvatures (present at birth) and secondary curvatures (formed after birth). The parts of the fetal curvature are the thoracic and the sacrococcygeal curve; these are primary. The cervical curve and the lumbar curve are secondary, occurring after the child is older and begins to stand and walk. Disorders of the spine include kyphosis (forward curvature of the thoracic region), lordosis (backward curvature of the lumbar region), and scoliosis (lateral curvature of anywhere in the spinal column).

VERTEBRAE The vertebrae vary in size and shape, following a similar structural pattern. Each has a body, a vertebral arch, and a total of seven processes. Figure 41 illustrates the anatomy of the typical vertebra:

The bone has a round cylindrical part and a vertebral arch, which faces to the back. The arch has four parts, the left and right pedicles and the left and right laminae. The large opening between the vertebral arch and body is the vertebral foramen, which has the spinal cord going through it. Spinal nerves pass through a passageway called the intervertebral foramen, which is formed by the pedicles of adjacent vertebrae. There is a transverse process on each side of the vertebral arch (which are paired and project laterally). A single spinous process projects toward the back down the middle of the back. These attach several crucial back muscles. There is an inferior articular process and a superior articular process that attach to the bone above and below the vertebra. These articular processes determine how the vertebrae will connect to one another and how the bones move in comparison to one another.

COCCYX AND SACRUM The sacrum is a triangular bone that is wider at the top and has a point at the base for the attachment of the coccyx. It is formed by the fusion of five sacral vertebrae, which does not begin until after 20 years of age. There is a bumpy ridge, called the median sacral crest, which is the remnant of fused spinous processes. The lateral sacral crest is made from the fusion of the transverse processes. The sacral promontory is the lip of the superior base of the sacrum and joins the sacrum to the ilium in the pelvis. The coccyx is referred to as the tailbone and is derived from four small coccygeal vertebrae. It may bear some weight when sitting.

THE INTERVERTEBRAL DISCS These are the structures that provide cushion between vertebral bodies. It allows for movement between the vertebrae. They are fibrocartilaginous pads that have an outer anulus fibrosis and an inner nucleus pulposus. The inner part is more gel-like and the outer part is fibrous. The discs become thinner with age as they lose body water. For this reason, the individual will lose body height, flexibility and range of motion. A ruptured or “slipped” disc

happens when the outer anulus fibrosus becomes weakened and leaks the contents of the nucleus pulposus out into the spinal canal or the intervertebral foramen. The adjacent vertebrae are connected by ligaments that run the length of the vertebral column. The anterior longitudinal ligament runs around the anterior side of the vertebral bodies and resists backward bending. The supraspinous ligament is located on the back side of the vertebral column and supports the spine during forward bending. It forms the nuchal ligament at the top of the spine, where the spine attaches to the back of the skull. There is also a posterior longitudinal ligament that is found inside the vertebral column. Behind the spinal cord inside the spinal column is the ligamentum flavum that connects the lamina of the adjacent vertebrae.

RIBCAGE AND STERNUM The thoracic cage is part of the axial skeleton. It consists of twelve paired ribs and the sternum or breastplate. The ribs are all attached to the twelve thoracic vertebrae; its function is to protect the heart and the lungs. The sternum has three parts: the manubrium, the body, and the xyphoid process. The manubrium is at the top and is a wide/flat bone. The top of it has a shallow, U-shaped border called the jugular (suprasternal) notch. On either side of it is the clavicular notch, where the sternoclavicular joint is located (the joint between the sternum and the clavicle). The first ribs have attachments to the manubrium. The body of the sternum is the largest part. It joins the manubrium at the sternal angle, forming a slight bend. The second rib attaches to the sternal angle. Ribs three through seven will attach to the sternal body; below this is the xyphoid process, which is mainly cartilaginous until a person reaches the middle age years of their life. Ribs are not long bones rather curved, flat bones that form the wall of the thorax. They each articulate in the back to the twelve thoracic vertebrae, attaching anteriorly to the sternum via the costal cartilages. Only ribs 11 and 12 are free-floating and do not connect anteriorly. The

head of the rib is the posterior/back part. The rib curves around to the front. There is a costal groove on the inferior border of the rib where the blood vessels and nerves run.

APPENDICULAR SKELETON The appendicular skeleton consists of the limb bones plus the parts of the body that connect the limbs to the body—the shoulder girdle or pectoral girdle and the pelvis. Figure 42 represents the appendicular skeleton:

THE SCAPULA AND CLAVICLE The scapula, or shoulder blade, is located overlying the upper back. It is supported by the clavicle, which is located in the upper anterior chest. These two bones are connected and form the pectoral girdle, which connects the upper limbs to the body. The clavicle is considered a long bone and serves to anchor several muscles that support the scapula. It holds the shoulder joint in position, while allowing for the maximal amount of freedom of motion of the joint. Its function also includes protecting crucial underlying vessels and nerves as they pass between the trunk of the body and the upper limb. There are two joints that are part of the clavicle: the medial sternoclavicular joint and the lateral acromioclavicular joint. The clavicle is the most commonly broken bone in the body. It occurs when a person falls into an outstretched arm or when there is a lateral blow to the shoulder. The sternoclavicular joint is very strong so, after an injury, the bone breaks rather than dislocating the joint. The segments of broken bone also tend to overlap because of the weight of the arm and shoulder acting on the bony fragments. The scapula anchors the upper limb to the body and is located on the back of the shoulder. It is surrounded by multiple muscles and articulates with the humerus and the clavicle. The bone is triangular with a superior, medial, and lateral border. The three corners of the triangle are the superior angle (medially-located), the inferior angle, and the glenoid cavity/glenoid fossa (that articulates with the humerus). It has two large projections, the coracoid process and the acromial process. The coracoid process is anchored to the clavicle by a strong ligament. The acromial process forms the acromioclavicular joint. Figure 43 illustrates the scapula and its projections:

The acromioclavicular (AC) joint transmits forces from the upper arm to the clavicle. It has relatively weak ligaments so that a fall on the outstretched hand and elbow will often stretch or tear these ligaments. The coracoclavicular ligament is the strong ligament around this joint; it can become injured with a lateral blow to the shoulder, resulting in a dislocation of the AC joint. This is also referred to as a shoulder separation injury.

UPPER LIMB There are three regions in the upper limb. These are the arm, forearm, and hand. There is a total of 30 bones in each upper limb. Figure 44 shows what these bones look like:

The humerus is the only bone in the upper arm area. Its proximal end is the head of the humerus, which is a ball to a ball-and-socket joint. There is a greater and lesser tubercle in this area that serve as shoulder joint muscles. The distal end of the humerus is flatter and has two epicondyles: the medial and lateral epicondyle. There are two articulations distally in the humerus: with the radius and with the ulna. The trochlea articulates with the ulna bone, while the capitulum articulates with the radius bone. There are several depressions: the coronoid fossa, the radial fossa, and the olecranon fossa, which allow for extension and flexion of the forearm so that the forearm bones do not bump into the humerus. The ulna is the forearm bone on the side of the little finger. The proximal end looks like a crescent wrench with a C-shaped trochlear notch that articulates with the trochlea of the humerus. It has a radial notch proximally that provides the joint to the radius called the “proximal radioulnar joint.” The olecranon process of the ulna forms the tip of the elbow. Along the shaft of the ulna is the interosseus membrane between the radius and ulna. The head of the ulna is actually the distal end. It has a styloid process that unites the distal aspects of the ulna and radius. The radius is the forearm bone on the lateral or thumb side of the forearm. The head is located near the elbow and articulates with the capitulum of the humerus. Like the ulna, there is a ridge for the interosseus membrane between the radius and the ulna. The distal end of the radius connects or articulates with two carpal (wrist) bones to make the radiocarpal joint or wrist joint. There are two rows of eight total carpal bones. The proximal row involves the scaphoid, lunate, triquetrum, and pisiform bones. The most distal row involves the trapezium, trapezoid, capitate, and hamate bones. Figure 45 shows the wrist bones and the bones of the hand:

The metacarpal bones are five long bones that form the hand and the thumb. They are each connected to the carpal bones in the wrist to form the carpometacarpal joint. The distal end of each metacarpal bone is the metacarpal phalangeal joint, which forms the first joints of the thumb and fingers (the knuckle bones). These bones are numbered 1 through 5, starting with the thumb metacarpal. The thumb metacarpal is separate from the rest of the bones in order to allow for thumb mobility. There are 14 phalanx bones (called phalanges) in the hand. The thumb has two phalanges (a proximal phalanx and a distal phalanx), while the other digits have three phalanges each (a proximal phalanx, a middle phalanx, and a distal phalanx). These are all connected to one another at several joints, known as the interphalangeal joints.

THE PELVIC GIRDLE The pelvic girdle is also referred to as the hip girdle. It is formed by a single fused bone called the hip bone. This is the attachment point for each of the two lower limbs. The hip bone is connected to the axial skeleton by an attachment to the sacrum at the sacroiliac joint. The pelvic girdle is largely immobile and is built for weightbearing. The three parts or segments to the pelvic bone are the ilium, the ischium, and the pubis. The ilium is the largest part. It is fan-shaped and connects the immobile sacroiliac joint. The superior iliac crest is the upper margin of the ilium called the iliac crest. Figure 46 shows the pelvic bone and its connections:

The ischium forms the posterior and lateral part of the hip bone. There is a tuberosity on the inferior portion, called the ischial tuberosity, which attaches the posterior thigh muscles and carries the weight of the body when a person is sitting. The pubis is the anterior part of the hip bone. It is connected in the middle to the other pubis by the pubic symphysis. There is a circular portion or hole in the pelvis made from the ischium and pubis, which form out of the 95

superior and the inferior pubic ramus. Each of the three parts of the pelvic bone converge to form the acetabulum—a cup that forms the joint between the pelvis and the femur. There are two regions that are enclosed by the bony pelvis. The superior part is called the greater pelvic cavity or “false pelvis,” which houses the small and large intestines. Inferiorly is the “true pelvis,” which is also referred to as the lesser pelvis. It contains the bladder and other pelvic organs. The pelvic brim (also called the pelvic inlet) is the upper margin of the lesser pelvis and the lower margin of the greater pelvis. The pelvic brim is known as the pelvic inlet, while the inferior part of the lesser pelvic cavity is called the pelvic outlet.

THE LOWER LIMB There are three regions in the lower limb: the thigh, the leg, and the foot. There are 30 bones in the lower limb, including the femur, patella, tibia, fibula, tarsal bones, metatarsal bones, and phalanges. Figure 47 shows the bones of the lower limb:

The femur is the only bone in the thigh. The head of the femur is the rounded proximal end that articulates with the acetabulum to form the hip joint. The greater trochanter is on the outside of the femur at the proximal end, while the lesser trochanter is the bony prominence on the

medial projection of the proximal femur. These are muscle attachments that move the thigh and leg. Distally, the femur has a lateral condyle and lateral epicondyle, as well as a medial condyle and medial epicondyle, that help form the articular connection to the tibia and fibula at the knee joint. The condyles form the actual joint, while the epicondyles form muscle attachments. Between the condyles is the intercondylar fossa, which is a deep depression that the patella sits in. The patella or kneecap is the largest sesamoid bone in the body, being incorporated into the tendon on the anterior part of the knee. The patella articulates with the patellar surface of the femur, preventing rubbing of the tendon against the distal femur. It also lifts the tendon away from the knee joint, which increases the leverage of the quadriceps femoris muscle across the knee joint. The patella does not articulate with the tibia. The tibia or shin bone is the medial bone of the leg—much larger than the fibula, which is its paired bone in the lower leg. The tibia is the main weight-bearing bone of the lower leg and can be palpated down the entire aspect of the medial leg. The proximal end has a medial and lateral condyle that are smooth and flat, articulating with the femur to form the knee joint. The tibial tuberosity is where the inferior patellar ligament attaches. There is a long interosseous membrane that acts as a connection between the tibia and the fibula. At the distal end is the medial malleolus or the medial ankle prominence. The fibula is the small outer or lateral bone in the lower leg. It does not bear weight but acts to attach muscles around the lower leg so it cannot be palpated, except at the proximal and distal ends. It articulates with the lateral tibial condyle to form the proximal tibiofibular joint. The distal end is palpated as the lateral malleolus or the outer ankle prominence. There are seven tarsal bones that form the proximal half of the foot. The talus is the most superior bone in the ankle and forms the ankle joint with the tibia and fibula. Inferiorly, it connects with the calcaneus, which is the heel bone and the largest bone in the foot. The calcaneus forms the weightbearing part of the foot. The cuboid bone, the navicular bone, and

three cuneiform bones also make up this part of the hind and mid-foot. Figure 48 shows the bones of the foot:

There are five metatarsal bones that connect to the more proximal bones of the foot. These are labeled 1-5, starting with the great toe side. Both the head of the first and the head of the fifth metatarsal can be felt on either side of the foot as prominences of the foot. There are 14 phalanges that are arranged similarly to the fingers. The toes are numbered like the metatarsals with the hallux being known as the big or great toe. The hallux has two phalanges, while the rest of the toes have the three phalanges.

JOINTS A joint or articulation is the place where two bones or bone and cartilage come together to make a connection. There are several types of joints, some of which are moveable and others are immoveable. The immoveable joints serve mainly a protective function—to protect internal structures and organs and to give the body some stability. Moveable joints allow for body motion. The structural classification of joints involves whether or not the joint is fibrous or contains cartilage. There are three structural joint classifications: 1) a fibrous joint, where adjacent bones are united by fibrous connective tissue; 2) a cartilaginous joint, where fibrocartilage or hyaline cartilage connects the two bones; and 3) a synovial joint, where the two bones

articulate but do not directly connect. Instead, there is a synovial fluid space between the articulating surfaces of the two bones. There are many different types of joints according to the functional classification of joints. These consist of these types of joints: •

Synarthrosis—this is a nearly immobile joint or an immobile joint that includes sutures of the skull that protect the brain. The manubriosternal joint also acts as a synarthrosis.

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Amphiarthrosis—this is a limited-mobility joint that includes those joints that connect adjacent vertebrae. The joint moves slightly but together the entire spine can move a great deal. The pubic symphysis is an amphiarthrosis that is connected by fibrocartilage.

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Diarthrosis—this is a freely mobile joint that includes all the synovial joints of the body. These are found in the appendicular skeleton and allow for a wide range of motion. These joints can be uniaxial (move in one plane), biaxial (move in two planes), or multiaxial (moves in all three planes).

Typical uniaxial joints include the elbow, which only bends or straightens in one plane. The knuckle joint is a typical biaxial joint, in that it allows for bending at the knuckles and widening of the fingers. A typical multiaxial (or triaxial) joint is the hip joint, which can move in all directions. •

Suture—all the bones of the skull (besides the mandible) are joint by fibrous joints called a suture. There is fibrous material that connects the two bones together. These are considered synarthroses. Infants have more fibrous tissue and open areas between the bones, called fontanelles; these close in the first few years after birth as the skull bones get bigger. Some sutures will ossify ad become a synostosis, which means “joined by bone.” This happens late in life so that the suture lines gradually disappear.

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Syndesmosis—a syndesmosis is a fibrous joint in which two parallel bones are connect by connective tissue. An example of this is the interosseous membrane. This type of fibrous connection is seen between the tibia and fibula, and the radius and ulna. The purpose is to unite parallel bones so they don’t separate.

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Gomphosis—this is a special fibrous joint that connects the roots of the tooth with the alveola of the maxillary bone and mandible. They are affixed by the periodontal ligament. It is technically called a synarthrosis because it is an immobile joint.

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Synchondrosis—this is a cartilaginous joint where two bones are joined by hyaline cartilage or where the bone is connected by hyaline cartilage. A temporary synchondrosis is the epiphyseal plate, which ossifies after the person grows. The ilium, ischium, and pubis are also connected via synchondroses during childhood and adolescence.

SYNOVIAL JOINTS Synovial joints are the most common joint in the body. The knee joint is a synovial joint that is depicted in figure 49 in your guide:

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There is a joint cavity in the synovial joint that keeps the articulating joints from actually coming in contact with one another. This gives the joint its movement. Synovial joints are divided into six different types, including these: •

Pivot joint—this rotates around a single axis, which has a rounded portion of bone enclosed within a ring. The atlantoaxial joint between the first and second cervical vertebrae is a pivot joint. The proximal radioulnar joint is another pivot joint.

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Hinge joint—this is a uniaxial joint, such as the elbow joint that involves a concave end and a convex end of two bones.

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Condyloid joint—this is also called an ellipsoid joint; an example is the radiocarpal joint of the wrist and the knuckle joints. These are considered biaxial joints.

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Saddle joint—this involves articulating surfaces that are shaped like a saddle. These are biaxial joints, such as the first carpometacarpal joint at the base of the thumb. This is what allows for opposition of the thumb across the hand.

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Plane joint—this is a gliding joint with flat or slightly curved joints so that bones can slide against one another. These can move in more than one plane but are usually limited in movement by neighboring bones or ligaments. The intercarpal and intertarsal joints of the hand and foot, respectively, are plane joints.

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Ball-and-socket joint—this is a joint with the greatest range of motion. The shoulder and hip joint are both ball-and-socket joints.

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KEY TAKEAWAYS •

There are several types of bones, based on the shape of the bone.

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Bones have a diaphysis, metaphysis, and epiphysis.

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There are several types of bone cells, including osteoblasts, osteocytes, and osteoclasts.

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There are several hormones that control bone growth and development.

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The axial skeleton involves the skull, vertebrae, ribs, and sternum.

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The appendicular skeleton involves the extremities, the pectoral girdle, and the pelvic girdle.

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Joints of the body are divided according to different structural and functional components.

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QUIZ 1. How many named bones are there in the adult human body? a. 53 b. 103 c. 206 d. 314 Answer: c. There are 206 named bones in the adult human body? 2.

What type of bone category involves the carpal bones? a. Sesamoid bone b. Long bone c. Flat bone d. Short bone Answer: d. The carpal bones are considered short bones because they are short and cuboidal in nature, offering only a limited amount of motion.

Which structure is not considered a hole in the bone? a. Fossa b. Fovea c. Sulcus d. Tuberosity Answer: d. A tuberosity is a bone projection; the other choices are considered holes in the compact bone.

Which bone cell has mitotic activity and actually divides? a. Osteoclast b. Osteoblast c. Osteogenic cell d. Osteocyte 103

Answer: c. Of these, only the osteogenic cell, which is undifferentiated, gives rise to osteoblasts, which turn into osteocytes. Osteoclasts are derived from different cells. 5.

Which nutrient makes up the majority of bony tissue? a. Calcium b. Fluoride c. Magnesium d. Phosphorus Answer: a. Much of bone is calcified in the form of calcium-containing hydroxyapatite crystals. Calcium is the nutrient that makes up most of the bony tissue.

Which hormone is most responsible for decreasing calcium concentration in the bloodstream? a. Thyroxine b. Calcitonin c. Parathyroid hormone d. Growth hormone Answer: b. Calcitonin will decrease the calcium concentration by inhibiting the activity of osteoclasts.

Which bone does not make up the brain case? a. Ethmoid bone b. Sphenoid bone c. Maxillary bone d. Occipital bone Answer: c. Each of these makes up the brain case except for the maxillary bone, which is part of the facial bones and not the brain case.

How many lumbar vertebrae are there? 104

a. 5 b. 7 c. 12 d. 15 Answer: a. There are five lumbar vertebrae in the vertebral column. 9.

What bone is not considered a part of the appendicular skeleton? a. Humerus b. Sacrum c. Pelvis d. Femur Answer: b. The sacrum is actually a part of the axial skeleton, while the rest of the bones are a part of the appendicular skeleton.

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Which type of bone is the scapula? e. Long bone f. Sesamoid bone g. Irregular bone h. Flat bone Answer: d. The scapula is mainly a flat bone that is triangular in shape. It is located in the upper posterior chest wall and helps form the joint between the shoulder girdle and the humerus.

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CHAPTER FIVE: MUSCLES AND THE MUSCULAR SYSTEM This chapter begins with a discussion of muscles and tendons as well as the different types of muscle tissue. A discussion of the muscles of the head, neck, trunk, upper extremities, and lower extremities are included in this chapter.

TYPES OF MUSCLE TISSUE Muscle tissue is one of the four primary types of tissue in the body, consisting of three different types: skeletal, cardiac, and smooth muscle. The main quality of muscle tissue is excitability (the ability to become depolarized electrically). An action potential passes from one end of the cell to another, causing muscle contraction. Skeletal muscle is unique among these because it depends entirely on the nervous system, while the other types can be activated by hormonal or environmental stimuli. All muscles contract via the interaction of actin (which is a major muscle protein) and myosin (another major muscle protein). This function occurs in striated muscle cells (cardiac and skeletal muscle) after calcium ions interact with tropomyosin and troponin (which are muscle proteins that block actin-binding sites). Calcium is important in smooth muscle cells but it activates enzymes that activate myosin heads. When calcium is removed, the actin-binding sites are covered again. The actin and myosin are arranged regularly in all types of striated muscle. Skeletal muscle is multinucleated, while cardiac muscle fibers have 1-2 nuclei. These cardiac muscle cells are both physically and electrically connected so the muscle contracts as a unit, called a syncytium. Actin and myosin are not arranged in a regular fashion in smooth muscle cells and the muscle cell has just one nucleus. Because the muscle proteins in smooth muscle are not regular, there are no striations, and the muscle appears “smooth.” The main functions of skeletal muscle include:

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Movement about the joint

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Stopping movement in the act of maintaining posture

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Maintaining joint stability

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Allow urination, defecation, and swallowing to be under voluntary control

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Protecting internal organs

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Generation of heat for homeostasis

There are three layers of connective tissue that encloses skeletal muscle, including the epimysium, which is a dense connective tissue that allows a muscle to contract while still maintaining its structural integrity. It allows people to have separate muscles that move independently. The perimysium is a middle layer of connective tissue that binds muscle fibers into individual bundles called a fascicle. Within the fascicle is a layer of connective tissue and reticular fibers, known as the endomysium, which surrounds the muscle fibers themselves. Figure 50 shows what a skeletal muscle looks like:

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The different mysial tissues intertwine with the collagen of a tendon, while the tendon itself fuses with the periosteum that surrounds the bone. The tension created by the contraction of muscle fibers gets transferred through the mysial tissues, to the tendon, and finally, to the bone for the movement of the skeletal structures. The mysia may also fuse with a tendon-like sheet called the aponeurosis that connects to certain organs and can fuse with fascia, the connective tissue between skin and bony tissue.

SKELETAL MUSCLE FIBERS These muscle fibers are long and cylindrical. They can be as long as 30 cm in length and are built embryologically from myoblasts that fuse with hundreds of myoblasts to form multinucleated skeletal muscle fibers. The multiple nuclei allow for multiple gene copies and a great deal of proteins and enzymes being produced—all of these necessary for muscle contraction. There are special terms used to describe muscle cells that start with the term “sarco,”which means flesh. The plasma membrane of muscle fibers is called the sarcolemma; the cytoplasm is called the “sarcoplasm,” and the smooth endoplasmic reticulum is called the “sarcoplasmic reticulum” or SR. The SR releases and retrieves, stores, and releases the necessary calcium ions for the contraction of muscle fibers. Skeletal muscle is divided into sarcomeres, which is a packet of actin and myosin, along with their regulatory proteins (troponin and tropomyosin). The sarcomere is the functional unit of the muscle fiber; it is bundled in the muscle cell’s myofibril that runs the entire length of the fiber, attaching to the sarcolemma at the end of the muscle fiber. One muscle fiber contains hundreds to thousands of myofibrils, and each myofibril consists of thousands of sarcomeres. Sarcomeres do not run the length of the muscle fiber but are attached to Z-discs that anchor the actin myofilaments. Figure 51 illustrates what a sarcomere looks like:

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The actin, along with the troponin-tropomyosin complex, consists of the “thin filament” of the sarcomere. The myosin strands project from the center of the sarcomere, extending toward the Z-discs; these are thicker and are called thick filaments.

THE NEUROMUSCULAR JUNCTION AND MUSCLE CONTRACTION The neuromuscular junction (NMJ) is where the nerve ending meets the muscle fiber. This is where the motor neuron initially sends a signal to the muscle cell. Each muscle cell is innervated separately and has a neuromuscular junction. It takes excitation at the NMJ for the skeletal muscle to contract. While all cells of the body have an electrical gradient across the

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membrane, only muscle and nerve cells use these potentials to create electrical currents. The currents are small but they are additive and result in muscle contraction. An action potential is an electrical signal that crosses a membrane as a wave. This allows a signal to be transmitted over long distances. Via what’s called “excitation-contraction coupling,” the electrical signal travels along the sarcolemma, resulting in a release of calcium ions from the sarcoplasmic reticulum. The calcium interacts with the shielding proteins (troponin and tropomyosin) in order to force them off the actin so that myosin can attach and pull the actin toward the center, shortening the muscle cell. Motor neurons that tell the skeletal muscle fibers to contract will originate in the spinal cord or brainstem (in the case of head and neck muscles) and will have very long axons that bundle together to form a single nerve that goes to a muscle. The action potential of the nerve cell travels to the NMJ and releases acetylcholine (which is a neurotransmitter or chemical messenger). The neurotransmitter travels across the synaptic cleft, binding to a receptor site, causing depolarization of the muscle fiber. When the membrane depolarizes, voltage-gated sodium channels open and sodium ions enter the cell, spreading the action potential along the membrane. The membrane quickly repolarizes and acetylcholine is degraded. If this doesn’t happen the muscle will continue to contract. This depolarization is the “excitation” portion of the excitation-contraction coupling. There are invaginations of the membrane (called T-tubules) that put the membrane as close to the sarcoplasmic reticulum as possible. A T-tubule and the SR membranes it attaches to is called a “triad,” which surrounds the myofibril in the muscle fiber. The T-tubules carry the action potential into the cell’s interior, allowing for calcium to come out of calcium channels in the sarcoplasmic reticulum. This initiates the “contraction” part of the process of contracting a muscle cell. ATP (the energy of the cell) helps sustain the muscle contraction by keeping the actin and myosin engaged. As long as ATP is present, the muscle can stay contracted. Only the stoppage of the action potential causes the muscle to stop contracting; however, running out of ATP will fatigue the muscle.

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Within the sarcomere, the thin actin fibers slide past the thick myosin fibers. This can happen only when calcium is present in the sarcoplasm (which, in turn, only happens when the action potential reaches the sarcoplasmic reticulum). Tropomyosin prevents actin from binding to myosin. The tropomyosin exists with troponin as a complex. Troponin binds calcium and allows tropomyosin to release its shielding of the actin binding sites. The actin binds to myosin “heads” and is pulled toward the center of the sarcomere. ATP energy is required to keep this process ongoing so the muscle fiber shortens. ATP allows the myosin and actin to disengage and reengage in order to pull the actin fiber over a longer distance. Muscle fatigue happens when a muscle can no longer contract. As ATP stores diminish, muscle function goes down and lactic acid builds up as energy is created by means of glycolysis versus aerobic respiration. Glycolysis continues without oxygen and results in the creation of less ATP. The downside is that lactic acid is a byproduct of these reactions, leading to muscle pain, or stiffness, during conditions of muscle fatigue. Relaxation of a skeletal muscle happens when the action potential stops. The muscle fiber membrane repolarizes, closing the calcium-releasing gates in the sarcoplasmic reticulum. There are pumps that move calcium back into the SR, resulting in coverage of the actin binding sites on the thin filaments. The cross-bridges between the actin and myosin stop and the muscle loses its tension. Muscle strength is partly genetically-determined because the number of muscle fibers in a muscle is the same throughout life. Hormones and stress on a muscle can increase the numbers of sarcomeres and myofibrils in the muscle, which will bulk up the muscle. A lack of muscle use causes atrophy of the muscle, with fewer sarcomeres and fewer myofibrils.

MUSCLE STRUCTURE In order to move the skeleton, the tension created by muscle fiber contraction in skeletal muscle is transferred to the tendons. Tendons are strong bands of connective tissue that attach muscles to bones. The skeletal muscle must be attached to a fixed part of the skeleton,

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called the origin of a muscle. The insertion of a muscle is the part that attaches to the bone being pulled. The agonist muscle is the primary mover of a specific action of a joint. It can be assisted by a synergist, which is a “helper muscle.”. A synergist can also be a “fixator muscle” that stabilizes the bone that is the attachment for the agonist’s origin. An antagonist muscle opposes the action of the agonist. Antagonists help maintain a limb’s position and control rapid movement of an agonist muscle. Some examples of agonist/antagonist pairs in the human body: •

Biceps brachii versus triceps brachii—these are two muscles in the upper arm. The biceps flexes the forearm, while the triceps extends the forearm.

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Hamstrings versus quadriceps—these are muscles of the thigh. The hamstrings flex the leg, while the quadriceps muscles extend the leg.

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Flexor digitorum superficialis and the flexor digitorum profundus versus the extensor digitorum muscles—the first two muscles flex the digits (fingers) and the hand at the wrist, while the extensor digitorum extends the fingers and hand at the wrist. These muscles are located in the forearm.

Some muscles do not pull against the skeleton to allow for skeletal movements. An example of this is the muscles that produce facial expressions. These muscles insert and have their origins in the skin so that muscles change the shape of the face and facilitates facial expressions.

FASCICLE ARRANGEMENTS A bundle of muscle fibers covered by the perimysium is called a fascicle. The arrangement of the fascicles determines how a muscle looks and acts. These are some common fascicle arrangements: •

Parallel—the fascicles are arranged in a parallel fashion, which is the case in most skeletal muscles. Some form a round mass that tapers at both ends into tendons but they are basically parallel fascicles.

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Circular—these lead to circular muscles, also known as sphincters. The contraction causes the sphincter to close, while the relaxation causes the sphincter to open. The orbicularis oris muscle around the mouth is a sphincter.

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Pennate—these are muscles that are splayed out in a feather arrangement. Because the muscle is arranged this way, it cannot move a tendon very far but is tense for its size. A unipennate muscle has fascicles on one side of the tendon (such as the extensor digitorum muscle). A bipennate muscle has fascicles on both sides of the tendon. In some cases, the muscle can be multipennate (such as the deltoid muscle, which covers the shoulder).

MUSCLES OF THE HEAD AND NECK The muscles of the head and neck are “axial muscles.” These include muscles of facial expression. Remember that the origin of a muscle does not move so muscles of facial expression have their origin in the skull surface. The insertion is the place where the muscle ends, which is in the connective tissue and dermis of the skin. This causes movement of the skin to create facial expression. The muscles of the face can be seen on figure 52:

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Two circular muscles of the face are the orbicularis oris and the orbicularis oculi (that closes the eye). The occipitofrontalis muscle moves both the scalp and the eyebrows. This muscle has two bellies (across the front) and across the occiput (back of the head). These are joined by the epicranial aponeurosis (a band of connective tissue across the top of the head. The buccinator muscle is in the cheek and allows for chewing and other mouth movements. There are several small muscles in the face that control minute motions of the face. Extrinsic eye muscles move the eyeball in all directions. They insert in the outer surface of the white part of the eye and originate in the bones of the orbit. There are several muscles that have this function, including the superior rectus, inferior rectus, lateral rectus, medial rectus, inferior oblique, and superior oblique muscles. The levator palpebrae superioris opens the eyes, while the orbicularis oculi muscle closes the eyes. Muscles that move the lower jaw include muscles of mastication or chewing. The main chewing muscle is the masseter muscle, which closes the mouth. It is assisted by the temporalis muscle, which pulls back the mandible. The lateral pterygoid opens the mouth and moves the mandible from side-to-side. The medial pterygoid muscle closes the mouth and helps move the jaw from side-to-side. There are muscles that move the tongue for tasting food, chewing, and swallowing. There are both intrinsic and extrinsic tongue muscles. Intrinsic muscles insert into the tongue and allow the tongue to change its shape. Extrinsic muscles include the styloglossus, genioglossus, palatoglossus, and hyoglossus. They originate in the place where the muscle indicates (for example, the hyoglossus originates in the hyoid bone) and end in the tongue. Muscles of the anterior neck help in swallowing and speech by controlling the position of the hyoid bone and larynx (voice box). There are suprahyoid muscles (above the hyoid bone) and infrahyoid muscles (below the hyoid muscle). The suprahyoid muscles raise the hyoid bone and the larynx, along with the floor of the mouth. These include the digastric muscle, the stylohyoid muscle, the mylohyoid muscle, and the geniohyoid muscle.

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The infrahyoid muscles are also called the strap muscles. They depress the hyoid bone to control the laryngeal position. These include the omohyoid muscle, the sternohyoid muscle, and the thyrohyoid muscle. They change the tone of a person’s voice.

MUSCLES THAT MOVE THE HEAD There are neck muscles that control the movement of the head. They cause flexion, extension and rotation of the head. The major muscle that does this is the sternocleidomastoid muscle. It laterally flexes and rotates the head. It originates in the sternum and clavicle and inserts in the temporal bone at the mastoid process and in the occipital bone. The semispinalis muscle rotates and tilts the head backward. The splenius capitis muscle rotates and tilts the head backward and to the side. The longissimus capitis muscle rotates the head and tilts the head backward.

MUSCLES OF THE POSTERIOR NECK AND BACK The posterior muscles of the neck are primarily concerned with movement of the head, particularly neck extension. The splenius muscles originate in the midline and run laterally and superiorly to their insertions. The splenius capitis inserts in the head and the splenius cervicis extends onto the cervical area. They can extend the head, laterally flex it, and rotate it. The erector spinae muscle group forms the mass of muscles in the back, being the primary extensor of the vertebral column. There are several muscles in this group, including the iliocostalis, the longissimus, and the spinalis muscle groups. The transversospinales muscles run from the transverse processes to the spinous processes of the vertebrae. The semispinalis muscles include the semispinalis capitis, semispinalis cervicis, and semispinalis thoracis. These act in the head, neck, and thorax, respectively, while the multifidus muscle act in the lumbar region. They extend and laterally flex the vertebral column. The segmental muscle group stabilizes the vertebral column and bring together the spinous and transverse processes of consecutive vertebrae. There are scalene muscles—anterior scalene,

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middle scalene, and posterior scalene muscle—which flex, laterally flex, and rotate the head. They also contribute to deep inhalation.

MUSCLES OF THE TRUNK There are four pairs of abdominal muscles covering the anterior and lateral abdominal wall. These include the rectus abdominis, transverse abdominis, internal obliques, and external obliques. These are the muscles you need to know about: •

External and internal obliques—these direct twisting at the waist and side bending of the vertebral column. They are seen in the lower ribs to the pelvis.

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Transverse abdominus—these will squeeze the abdomen and are important in defecation and urination. It is seen from the lower ribs to the pubis.

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Rectus abdominis—these help the body to sit up. It starts in the pubis and ends in the sternum and lower ribs.

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Quadratus lumborum—this muscle causes side bending. It is seen from the ilium up to the ribs.

Figure 53 shows the abdominal muscles:

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The linea alba is a white, fibrous band that is made from the rectus sheaths that join in the anterior midline of the body. They enclose the rectus abdominis muscles that extend upward from the pubis to the sternum. Three transverse bands of collagen fibers are tendinous intersections that look like six-pack abs when the person does many sit-ups. The muscles of the chest will facilitate breathing by changing the size of the thoracic cavity. Inhalation causes the chest to rise and expansion of the lung cavity. Exhalation causes the chest to fall. These are the major muscles of the chest/thorax: •

Diaphragm—this is the main breathing muscle used in inhalation and exhalation. It originates in the sternum and lower ribs, and ends in the central tendon, causing compression and expansion of the lung cavity.

•

External intercostals—these are between each rib and are secondary muscles involved in inhalation and exhalation.

•

Internal intercostals—between the ribs and are important in forced exhalation.

The diaphragm contracts and relaxes and separates the thoracic and abdominal cavities. At rest, it is dome-shaped and convex when looking at it from above. It contracts and flattens, increasing the negative space in the chest cavity, allowing for lung expansion. There are three openings in the diaphragm for the passage of the vena cava, esophagus, and aorta/thoracic duct. There are three sets of muscles, called the intercostal muscles, which exist between the ribs and assist in the breathing process. There are eleven pairs of external intercostal muscles, used in inspiration. There are also eleven pairs of internal intercostal muscles, used for expiration, particularly forced expiration. The innermost intercostals are the deepest chest muscles that act as synergists for the internal intercostal muscles. There are many muscles of the perineum and pelvic floor. The pelvic floor is a sheet of muscles that define the bottom of the pelvic cavity. There is a structure called the “pelvic diaphragm,” which spans the pubis and coccyx. It is made from three muscles: the levator ani muscles (pubococcygeus and iliococcygeus) and the ischiococcygeus muscle. These support the pelvic

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organs and have openings that include the anal canal, vagina (in women), and urethra. Figure 54 illustrates the perineal musculature in females:

The perineum is diamond-shaped and overlies the pelvic diaphragm. It is divided into the anterior triangle or “urogenital triangle” and the posterior triangle or the “anal triangle,” which contains the anus. There are deep and superficial layers to these muscles. Women have two extra muscles: the compressor urethrae and the sphincter urethrovaginalis, which close the vagina. In men, there is an extra deep transverse perineal muscle that plays a role in ejaculation. Superficial muscles in the perineum include the superficial transverse perineal muscle (which supports the perineal body), the bulbospongiosus (which compresses the urethra), and the ischiocavernosus (which helps to maintain an erection in males). There are also deep sphincter muscles: the external urethral sphincter and the external anal sphincter.

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MUSCLES OF THE UPPER EXTREMITY Muscles of the upper extremity include pectoral girdle muscles, arm-moving muscles, forearmmoving muscles, and muscles of the hand and wrist. Remember that the pectoral girdle or shoulder girdle is the lateral aspect of the scapula and clavicle as well as the proximal humerus. These muscles allow the shoulder to move in multiple directions.

MUSCLES OF THE PECTORAL GIRDLE These muscles are located on the anterior or posterior thorax. The anterior muscles include the subclavius, serratus anterior, and the pectoralis minor. The posterior muscles include the trapezius, rhomboid major, and rhomboid minor. Figure 55 shows the shoulder muscles.

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Muscles of the shoulder include the following:

Subclavius—this is an anterior muscle that stabilizes the clavicle during movement of the shoulder. Pectoralis minor—this is an anterior muscle that depresses the scapula and elevates the ribs, during rotation of the shoulder anteriorly. It also assists with inhalation. Serratus anterior—this is an anterior muscle that moves the arm from the side of the body to the front of the body and assists with inhalation. Trapezius—this is a large posterior muscle that elevates the shoulders and pulls the shoulder blades together. It tilts the head backward. Rhomboid major—this is a posterior thoracic muscle that stabilizes the scapula during pectoral girdle movement. It acts on the scapula. Rhomboid minor—this is a posterior thoracic muscle that stabilizes the scapula during pectoral girdle movement by acting on the scapula. The muscles that move the humerus are the actual moving muscles of the arm. These will cross the shoulder joint and will move the humerus bone. The pectoralis major muscle and the latissimus dorsi muscle are axial muscles that cover the thorax and back, respectively. These are thick and fan-shaped muscles that move the humerus. The pectoralis major muscle brings the elbows together and the latissimus dorsi muscle moves the muscles back. There are numerus scapular muscles that also move the humerus. They include the following:

Deltoid muscle—lifts the arm at the shoulder. Subscapularis—assists the pectoralis major. Supraspinatus—rotates elbow outward. Infraspinatus—rotates elbow outward. Teres major—rotates elbow outward. Teres minor—assists the infraspinatus in rotating the elbow outward. Coracobrachialis—moves elbow up and across the chest. 120

It should be noted that the tendons of the subscapularis, supraspinatus, teres minor, and infraspinatus all connect at the top of the shoulder, forming the rotator cuff, which encircles the shoulder joint. This tendon mass can get inflamed and pinched, and may tear away from the bone, especially in people who overuse or injure the shoulder. There are muscles that move the forearm. Figure 56 illustrates some of these muscles:

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The forearm consists of the radius and ulna. There are four actions that can occur in the elbow joint: flexion, extension, supination, and pronation. A summary of these muscles is listed here: •

Biceps brachii—this muscle flexes and supinates the forearm at the elbow.

•

Brachialis—this muscle flexes the forearm.

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Brachioradialis—this assists the flexion of the forearm by stabilizing the elbow.

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Triceps brachii—this extends the forearm (straightens it).

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Anconeus—this muscle aids in extending the forearm by stabilizing the elbow.

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Pronator teres—it pronates the forearm (turns the palm down).

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Pronator quadratus—assists in pronating the forearm.

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Supinator—this muscle supinates the forearm.

The muscles that move the wrist, hand, and fingers are many. There are extrinsic and intrinsic hand muscles. The intrinsic hand muscles originate in the palm. Figure 57 illustrates the muscles of the hand:

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These are the muscles that move the hand and wrist. Some are located in the forearm, while others are in the hand. Superficial anterior compartment forearm muscles: •

Flexor carpi radialis—bends the wrist toward the body and tilts the hand away from the body.

•

Palmaris longus—helps to bend the hand up toward the shoulder.

•

Flexor carpi radialis—bends the hand up toward the shoulder and tilts the hand away from the body.

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Flexor digitorum superficialis—bends the fingers to make a fist.

Deep anterior compartment forearm muscles: •

Flexor pollicis longus—bends the tip of the thumb.

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Flexor digitorum profundus—bends the fingers to make a fist.

Superficial posterior compartment forearm muscles: •

Extensor radialis longus—straighten wrist toward the body and tilts the hand away from the body.

•

Extensor carpi radialis brevis—assists the extensor radialis longus muscle.

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Extensor digitorum—opens fingers.

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Extensor digiti minimi—extends the little finger.

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Extensor carpi ulnaris—straightens the wrist away from the body and tilts the hand toward the body.

Deep posterior compartment muscles: •

Abductor pollicis longus—moves and extends the thumb.

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Extensor pollicis brevis—extends the thumb.

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Extensor pollicis longus—extends the thumb.

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•

Extensor indicis—extends the index finger.

The tendons of the forearm muscles attach to the wrist and extend onto the hand. There are retinacula (singular is retinaculum) sheaths around the tendons at the wrist. The flexor retinaculum is across the palm and the extensor retinaculum is across the back of the hand. The intrinsic muscles of the hand both originate and insert within the hand. They allow the fingers to do slight movements. There are three groups of intrinsic hand muscles: the thenar muscles, the hypothenar muscles and the intermediate muscles. The thenar muscle form the rounded contour of the base of the thumb, which is called the “thenar eminence.” The hypothenar muscles form the hypothenar eminence (the rounded contour of the little finger) and act on the little finger. The intermediate muscles act on all the fingers. Thenar muscles include the abductor pollicis brevis (abducts the thumb), opponens pollicis (opposes the thumb), flexor pollicis brevis (flexes the thumb), and the adductor pollicis (adducts the thumb). Hypothenar muscles include the abductor digiti minimi (abducts the little finger), the flexor digiti minimi brevis (flexes the little finger), and the opponens digiti minimi (opposes the little finger). Intermediate muscles include the lumbricals (flex the fingers), palmar interossei (adduct the fingers), and the dorsal interossei (abducts and flexes the fingers at the MCP joint and extends the middle fingers at the IP joints).

MUSCLES OF THE LOWER EXTREMITY The appendicular muscles of the lower limb act on the pelvic girdle, the thigh, and the leg. The pelvic girdle has less movement about it because the pelvis is an immobile structure that stabilizes rather than moves the body. The gluteal muscles are in the buttocks and move the femur/thigh. These muscles are some of the strongest and largest muscles in the body. The largest of these is the gluteus maximus. There are two smaller muscles, including the gluteus medius and the gluteus minimus. The gluteus maximus is the main extensor muscle at the thigh, while the gluteus medius and gluteus minimus abduct the thigh. The tensor fascia lata will flex and abduct the thigh. The iliopsoas

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muscle group include the femur flexors and lateral rotators, including the psoas major and iliacus muscles. The lateral rotators include the piriformis muscle, the obturator internus, obturator externus, superior gemellus, and the quadratus femoris. An illustration of the leg muscles is seen in figure 58:

Adductors of the thigh include the adductor longus, adductor brevis, adductor magnus, and the pectineus muscles. Abduction of the thigh is lateral movement of the thigh; adduction is bringing together of the thigh; flexion is forward bending of the thigh; and extension is straightening and bending backward of the thigh. Rotation of the thigh can be inward (medial) or outward (lateral). There are multiple muscles of the thigh that move the femur, tibia, and fibula. There are deep connective tissue fascial planes that separate the thigh into the medial, anterior, and posterior compartments. The medial muscles adduct the femur at the hip. The adductor muscles of the

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thigh include the adductor longus, adductor brevis, adductor magnus, and pectineus, while the gracilis flexes and adducts the lower leg at the knee. Anterior compartment of the thigh includes the rectus femoris, vastus lateralis, vastus medialis, vastus intermedius, and the sartorius. The rectus femoris flexes the thigh and extends the tibia and fibula. The others will extend the tibia and fibula, except for the sartorius, which moves the back of the lower leg toward the buttocks. The posterior compartment of the thigh mainly flexes the leg at the knee. These include the biceps femoris, semitendinosus, and the semimembranosus. They also extend the thigh; some will laterally rotate while others will medially rotate the leg. The lower leg is divided into three deep compartments: the anterior, lateral, and posterior compartments. The anterior compartment of the leg will dorsiflex the foot or great toe. These include the tibialis anterior, extensor hallucis longus, and the extensor digitorum longus. The lateral compartment flexes and everts the foot; it includes the fibularis longus and the fibularis (peroneus) brevis muscle. In the posterior compartment of the lower leg, there are deep and superficial muscles. The superficial muscles are the gastrocnemius, soleus, tibialis anterior, and the plantaris. These flex the foot and/or invert the foot. The deep muscles include the popliteus muscle, the flexor digitorum longus muscle, the tibialis posterior, and the flexor hallucis longus. Intrinsic muscles of the foot will move the toes in various directions. The dorsal group includes the extensor digitorum brevis, which extend toes 2-5 (the great toe has a separate extender). The superficial layer of the plantar surface includes the abductor hallucis, flexor digitorum brevis, and the abductor digiti minimi. The second layer includes the quadratus plantae and the lumbricals. The third layer includes the flexor hallucis brevis, adductor hallucis, and the flexor digiti minimi brevis. The fourth layer includes the dorsal interossei and the plantar interossei.

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KEY TAKEAWAYS •

Muscle cells are electrically active, which ultimately causes actin to be pulled by myosin, which shortens the muscle.

•

Only skeletal muscle has a neuromuscular junction, which releases acetylcholine to cause muscle contraction.

•

There are agonist muscles, synergist muscles, and antagonist muscles in action around a joint.

•

The head and neck muscles include muscles of facial expression as well as muscles that flex, extend, and laterally bend or rotate the head.

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Trunk muscles act in breathing (which are in the thorax) and in movement of the trunk anteriorly (which are located in the abdomen).

•

Extremity muscles are best memorized in terms of their ability to flex, extend, rotate, abduct, and adduct the extremity.

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QUIZ 1. Which protein gets acted on in order to cause muscle contraction? a. Actin b. Myosin c. Tropomyosin d. Troponin Answer: a. Actin gets acted on and “pulled” by myosin, while tropomyosin and troponin block certain sites on the actin protein, preventing contraction. 2.

Which connective tissue surrounds the entire muscle in order to give it integrity as the muscle contracts? a. Endomysium b. Fascicle c. Epimysium d. Perimysium Answer: c. The epimysium is the dense connective tissue that surrounds the entire muscle and gives the muscle its integrity as it contracts in the body.

Which neurotransmitter or chemical messenger is present at the neuromuscular junction? a. Acetylcholine b. Serotonin c. Dopamine d. GABA Answer: a. While each of these is a neurotransmitter that acts at different nerve junctions, only acetylcholine is involved as the chemical messenger in the neuromuscular junction.

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What cell structure brings the action potential of the muscle cell to the interior of the cell? a. Sarcolemma b. Sarcoplasmic reticulum c. T tubule d. Z disc Answer: c. The T-tubule is an invagination of the sarcolemma so that the action potential can get to the interior of the cell so that the sarcomere can contract.

What type of fascicle arrangement is seen in the orbicularis oris muscle? a. Circular b. Multipennate c. Parallel d. Bipennate Answer: a. The orbicularis oris muscle is a circular muscle that controls the opening and shape of the mouth. The fascicles are arranged in a circular fashion.

Which muscle of the eye is not an extrinsic muscle that controls eyeball movement? a. Lateral rectus b. Orbicularis oculi c. Medial rectus d. Inferior oblique Answer: b. The orbicularis oculi muscle closes the eyelid but doesn’t control the actual eyeball movements.

Which is the main muscle used for sitting up? a. Rectus abdominis b. Transverse abdominis c. Quadratus lumborum d. External obliques 129

Answer: a. The rectus abdominis is the main “sitting-up” muscle; it runs from the pubis to the sternum and is used for sit-ups. 8.

Which set of muscles or muscle are/is the main muscle(s) of respiration? a. External obliques b. Diaphragm c. Internal obliques d. Innermost obliques Answer: b. Main muscle of respiration is the diaphragm, with the rest of the muscles being accessory muscles of breathing.

Which muscle does not rotate the elbow outward? a. Subscapularis b. Coracobrachialis c. Infraspinatus d. Teres major Answer: b. The muscles listed all rotate the elbow outward except for the coracobrachialis muscle, which instead helps bring the elbow across the chest.

10.

What muscle is the main flexor of the forearm? a. Triceps brachii b. Brachialis c. Biceps brachii d. Brachioradialis Answer: c. The biceps brachii is the main flexor of the forearm, assisted by the brachialis and brachioradialis muscle. The triceps brachii actually extends the forearm at the elbow.

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CHAPTER SIX: CENTRAL NERVOUS SYSTEM There are different types of brain cells—some of which conduct electricity and others that protect and support the electrically-active nerve cells. The gross anatomy and basic functions of the brain are covered in this chapter as well as the gross anatomy and basic functions of the spinal cord, which is also technically a part of the CNS or central nervous system. It should be noted that the nervous system is divided into the CNS (central nervous system) and PNS (peripheral nervous system), the latter of which will be discussed in the next chapter. The CNS located within the skull and vertebral column, and the PNS is outside of these structures (although there are exceptions).

BRAIN CELL TYPES AND FUNCTION There are two cell types in the whole of the nervous system: the neuron and the glial cell. Glial cells are of several types and provide a framework of tissue that supports the neuron and its actions; the neuron is electrically active and is the communication cell of the nervous system. Neuron structure is important to the function of the cell. There is a cell body (containing the nucleus and main cytoplasm structure) and extensions or processes. There is an axon, which connects the cell to its target cell, and at least one dendrite, which usually receives the impulse from another neuron (although there are exceptions). The gray matter has mainly nerve bodies and dendrites; the white matter mainly contains axons that are myelinated. Figure 59 illustrates what a nerve cell looks like:

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A localized collection of cell bodies of neurons in the CNS is called a nucleus, while the similar structure in the peripheral nervous system is called a ganglion. A bundle of nerve fibers or axons in the CNS is called a tract, while the same thing in the PNS is called a nerve. A single axon can be in a tract and later can be in a nerve. Neurons are the basis of nerve tissue, responsible for the passage of the electrical signal in the nervous system. There are a number of connections within the nervous system. The body of the neuron is referred to as the “soma,” which means “body.” Usually there is just one axon, which is a process that projects out of the soma to another nerve cell or electrically-active structure. Axons can repeatedly branch out to communicate with more than one cell. The communication point is called a synapse. Dendrites are also projections but these are more branched and usually receives information. Neurons are polar—the information goes in one direction. The axon hillock is where the axon emerges from the cell body; its cytoplasm changes to be called axoplasm. The axon hillock is also called the “initial segment.” Many axons are covered with myelin, which is made by glial cells. Myelin insulates the axon to allow for faster nerve impulse transmission. There is a gap between collections of myelin called nodes of Ranvier, which divides the axon into segments called axon segments. The axon terminal is the end of the axon, which ends at an enlargement called a “synaptic end bulb.” 132

TYPES OF NEURONS There are trillions of neurons in the nervous system and there are many types of these cells. They can be classified in several ways with names that are based on the type of polarity in the cell. Figure 60 shows the different types of neurons:

A unipolar cell has just one process that emerges from the cell. In humans, they are often referred to as “pseudo-unipolar” cells because true unipolar cells only exist in invertebrates. In humans, the axon often splits, with one split with dendrites and another split with the part of the cell that sends the signal to another neuron. These are exclusively sensory neurons. The cell bodies are always found in ganglia with dendrites in the periphery, taking up sensory information. The axon goes up into the CNS. Bipolar cells have two processes, which extend from each end of the cell body—usually on opposite ends of the soma. One process is the axon, while the other is the dendrite. These are not commonly seen in humans, except in the olfactory epithelium which assist with the sense of smell, and in the retina, where visual stimuli are received.

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Multipolar neurons are the most common type of neuron in humans. There is usually one axon and at least two dendrites. There is a subtype seen in the CNS called the “anaxonic neuron” that has no obvious axon. The cell still has projections but any of the projections can act as an axon at any given point in time. There are other classifications of neurons that depend on where the nerve cell is located in the body but these are less commonly seen.

TYPES OF GLIAL CELLS Glial cells are the type of cell found in the nerve tissue that act as supporting cells to the neurons. They are also referred to as neuroglial cells or “neuroglia.” There are six types of neuroglia (which were described in Chapter 2). Figure 61 shows what the different neuroglial cells look like:

Four of these cell types are seen in the CNS and two are seen in the PNS. A brief review of these cells is included here: •

Astrocyte—a supportive cell

•

Oligodendrocyte—a cell for insulation and myelination

•

Microglia—cells for phagocytosis and immune surveillance

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•

Ependymal cell—a cell that creates CSF (cerebrospinal fluid)

The astrocyte is star-shaped and have many processes coming from their cell body (which are not dendrites or axons). They interact with blood vessels, connective tissue, and neurons. They support by maintaining the concentration of chemicals in the extracellular space, by removing neurotransmitters, by contributing to the blood-brain barrier, and by reacting to tissue damage. The blood-brain barrier or BBB is what separates the CNS from the rest of the body. The BBB will allow nutrients in the CNS but other molecules will not be allowed into the brain. The brain has a special blood supply with little ability for molecules to pass through passively. Because of this, amino acids and glucose must be pumped into the CNS through active transport. Gases and ions can also get through the CNS. WBCs and larger molecules cannot get into the brain or spinal cord. Pharmaceuticals often have a limited ability to pass through the BBB. Oligodendrocytes have few branches (and thus the name). Each oligodendrocyte reaches out and surrounds an axon in order to insulate it with myelin. One such cell will make myelin for multiple axon segments or for different axons. Microglia are probably white blood cell types called macrophages that become microglia as part of early embryonic development. They encounter diseased or damaged cells and ingest/digest these cells or possibly pathogens. Because of their job, microglia are also called CNS-resident macrophages. An ependymal cell is a glial cell that filters the blood and turns it into cerebrospinal fluid or CSF, which is the fluid that circulates throughout the central nervous system. These cells line the ventricles in the CNS, which are embryological remnants of the neural tube. There is a specialized structure in the ventricles called the choroid plexus in which ependymal cells come into contact with blood vessels, where blood can be filtered. This makes the ependymal cells a part of the blood brain barrier. The ependymal cells are similar to epithelial cells in the CNS.

MYELIN The insulation for axons or “myelin” is made by the oligodendrocytes in the CNS and by Schwann cells in the PNS. Myelin is a lipid-rich substance that surrounds the axon to make a 135

sheath. The sheath allows for more rapid transport of the action potential down the axon. Myelin also provides important proteins that are important to the neuronal membrane. The myelin sheath can extend for 1-2 millimeters down the axon. It greatly widens the diameter of the axon.

ACTION POTENTIAL Neurons have receptors or dendrites that receive a signal that must reach a certain threshold in order to allow for the electrical impulse or “action potential” to propagate down the cell. The signal then passes from one cell to the next via a “neurotransmitter” or small cell that crosses the gap between the cells called a synapse. The neurotransmitter diffuses across the synapse to bind to a receptor protein located on a target neuron. This changes the electrical state of the target cell. This propagates the signal. Within the cortex and the CNS are upper motor neurons, which have their cell body in the brain or spinal cord. The cell in the spinal cord or ganglion that communicates with the PNS is called a lower motor neuron. As you learned in the previous chapter, there is a net negative charge (called the membrane potential) in the cell so that the cell is slightly negative inside the cell versus outside of the cell. This negative charge is only seen close to the membrane and is part of how the cell can generate an action potential. The ion channels (which pass ions like sodium and potassium) in the cells are closed when the cell is at rest with the concentration of sodium being ten times greater outside of the cell. Inside the cell, the potassium ion concentration is higher when compared to the outside. There is a -70-mV difference in charge between the inside and outside. This is called the “resting membrane potential.” The resting membrane potential is the steady state that is balanced by ion leakage and active ion pumping inside and outside the cell. To get the passage of an electrical signal throughout the cell, there needs to be a change in the membrane potential. This starts with the sodium channel opening, rushing ions into the cell and, because sodium is positively charged, the net

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negative charge is changed. This is called depolarization, resulting in a membrane potential of +30 mV. When the voltage changes, potassium channels open and the positively-charged potassium ion leaves the cells so that the net charge is -70 mV again; this is called repolarization. There is usually a slight overshooting that happens when the potassium leaves the cell, leading to a temporary hyperpolarization of the cell. The entire process of depolarization and repolarization is called the action potential. Figure 62 is what the action potential looks like:

What causes the action potential is the neurotransmitter binding to the cell and causing the sodium channel to be engaged and to open. In the case of sensory neurons, a physical stimulus activates the sensory receptor, causing the action potential to occur. The first type of sodium channel is called a “ligand-gated Na+ channel” and the second type of sodium channel is called a “mechanically-gated Na+ channel.” There is a third type of channel called the “voltage-gated Na+ channel.” This latter channel requires a certain threshold to be reached before the action potential can be propagated. If the threshold is not reached, there will be no action potential. Action potentials are “all or none.” 137

The voltage-gated sodium channel causes depolarization. There are actually two types of voltage-gated sodium channel gates. One is the activation gate, which opens when the membrane potential crosses a -55-mV level. The other gate type is the inactivation gate, which closes after a specific period of time. This inactivation gate is closed when the cell is at rest but, when the cell is activated, the gate opens to allow for depolarization. The inactivation gates are closed then—until the membrane potential passes the -55-mV level again. There is just one voltage-gated potassium channel that does not open as quickly as the sodium channel. It opens just as the sodium channel is peaking in order to repolarize the cell. As mentioned, it overshoots the resting membrane potential but the activity of the non-gated channels and the sodium-potassium pump in the membrane acts to correct this overshooting problem. It takes just 2 milliseconds for this entire cycle to take place. There is a slight refractory period in which no action potential that can occur. There are two phases of this period: the absolute refractory period (in which no action potential can start) and he relative refractory period (in which a stronger input is necessary to start an action potential). The action potential starts at the initial segment (the end of the axon), where there are a lot of voltage-gated sodium channels. The action potential is propagated by more voltage-gated sodium channels down the line will open to propagate the impulse down the cell’s dendrite or axon. Because of the refractory period, the propagation can only go in one direction. This leads to the polarity of the nerve cell. This propagation only applies to nonmyelinated axons. It propagates differently in myelinated cells. This is because there is no voltage-gated sodium channel activation on myelinated parts of the cell so they only open at the nodes of Ranvier. This allows for the stepwise transfer of the electrical impulse more efficiently down the cell axon. The nodes of Ranvier are particularly spaced so that the depolarization doesn’t fade off before the next node can be activated or depolarized. This is referred to as “saltatory conduction” versus the continuous conduction on nonmyelinated cells. The action potential leaps from one node to the next. The wider diameter of the axon, the faster is the propagation down the axon.

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SYNAPSES There are two types of connections between cells that are electrically-active. In a chemical synapse, there is a neurotransmitter (a chemical messenger) that is released from one cell, having an effect on another cell. In an electrical synapse, there is a direct connection between two electrically-active cells. Ions pass from one cell to the next. Of these two, the most common is the chemical synapse. The neuromuscular junction (NMJ) discussed already is an example of a chemical synapse. Synapses of all types have common features, including the following: •

Presynaptic element (vesicles and machinery to release the neurotransmitters)

•

Neurotransmitters (packaged into vesicles and sent out into the synapse)

•

Synaptic cleft (the space between the electrically active cells)

•

Receptor proteins (that receive the neurotransmitters on the postsynaptic cell)

•

Postsynaptic element (where the action potential takes place)

•

Neurotransmitter elimination or reuptake of these chemicals

Calcium is the key ion at the axon terminal (the end of the axons). These voltage-gated calcium channels open up and calcium concentration increases in the cell. This calcium interacts with the vesicles containing neurotransmitters in the presynaptic cell. It facilitates the merging of the presynaptic membrane, causing the release of neurotransmitter in the synaptic cleft. The synaptic cleft is a short distance between the cells so that the neurotransmitter can diffuse to the postsynaptic cell, binding specifically to the receptors in what is a specific chemical event. There are several neurotransmitter types that act specifically in parts of the brain and PNS. An example of this is the cholinergic system of the NMJ, which used acetylcholine as the main neurotransmitter. There are actually two types of cholinergic receptors: the nicotinic receptor (seen in the NMJ) and the muscarinic receptor. These two receptors are mutually exclusive.

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NEUROTRANSMITTERS There are several neurotransmitter systems besides the acetylcholine system. There are amino acid systems, such as the glutamate (or glutamatergic) system, the GABA (or GABAergic) system, and the glycine (or glycinergic) system. There is a pump system that recycles or takes up the amino acids after they have been acted on. There are biogenic amines, which are related to amino acids. An example of this is serotonin, which is made from tryptophan. This is a part of the serotonergic system. Like amino acids, serotonin is taken back up into the presynaptic cell after it has been used on the postsynaptic cell. Other biogenic amines that are neurotransmitters include epinephrine, norepinephrine, and dopamine. Only epinephrine and norepinephrine have the ability to bind to the same receptor. A neuropeptide is a neurotransmitter molecule made up of a small chain of amino acids. A small one is called met-enkephalin (which is 5 amino acids long), while a long one is betaendorphin (which is 31 amino acids long). They often act also as hormones, which are technically different in action to neurotransmitters, such as vasoactive intestinal peptide (VIP) and substance P. The effect of a neurotransmitter depends on what it does to the postsynaptic cell. Some are excitatory neurotransmitters, others are inhibitory neurotransmitters, while others do both, depending on what happens at the postsynaptic cell. Glutamate is always excitatory, while glycine and GABA are always inhibitory (because they cause hyperpolarization and not depolarization). The biogenic amines (dopamine, serotonin, etc.) have mixed effects on the postsynaptic cells. The effect relies entirely on the receptor. There are two types of receptors: 1) inotropic receptors and 2) metabotropic receptors. Inotropic receptors are ligand-gated ion channels, while metabotropic receptors cause metabolic changes within the cell. In the latter case, a neurotransmitter (or first messenger) binds to the receptor protein, causing the G protein in the cell membrane to become activated. The G protein is a GTP hydrolase that physically moves to activate the effector protein on the

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inside of the cell. This effector protein is an enzyme that creates a second messenger inside the cell. There are different types of second messengers, two of which are cyclic AMP and inositol triphosphate. These cause metabolic changes within the cell that modify ion channels, causing them to either open or close. Interestingly, these molecules also change genes in the nucleus which, in nerve cells, may be the basis of learning and memory inside the brain.

BRAIN STRUCTURE AND FUNCTION The CNS consists of the brain and spinal cord. There are four regions to the brain, the cerebrum, the diencephalon, the brainstem, and the cerebellum. Figure 63 shows what the brain anatomy looks like:

THE CEREBRUM The cerebrum is the largest part of the brain. The wrinkled part is called the cerebral cortex with the rest of the brain beneath that. The separation of the brain into the left and right hemisphere is called the “longitudinal fissure.” Deep inside the cerebrum is the corpus 141

callosum, which is the white matter that connects the two halves of the brain; it is the major pathway for communication between the hemispheres. The cerebrum is the “thinking” part of the brain and is responsible for emotion, memory, and consciousness. There are three nuclei deep in the cortex, called basal nuclei. These are responsible for cognitive processing—particularly, the planning of movements. There are nuclei important in learning, memory, emotion, and behavior. The cerebral cortex is a continuous layer of gray matter that covers the cerebrum and is responsible for higher cortical functions. A gyrus is the ridge seen on the cortex, while the sulcus is the groove between the two gyri. The fold pattern indicates the specific regions of the cerebral cortex. This extensive folding is necessary because the brain must fit within a small space so it needs to fold up. There is a lateral sulcus that separates the temporal lobe from the parietal lobe and frontal lobe. The central sulcus separates the frontal lobe and the parietal lobe. The occipital lobe has no anatomical border between it and the other lobes on the outside. There is, however, a parieto-occipital sulcus on the inside. There are 52 separate histologic areas that have been identified as “Brodmann’s areas,” first identified in the early 1900s but still in use today. These areas align very well with known functional areas of the brain. Areas of the occipital lobe are identified with vision; areas of hearing are associated with the temporal lobe. Memory (particularly long-term memory) is also associated with the temporal lobe as well. The parietal lobe is affiliated with somatosensation. The frontal lobe is primarily affiliated with motor functions. In the parietal lobe, just posterior to the central sulcus, is the postcentral gyrus, which is also referred to as the primary somatosensory cortex. This area processes sensations. Just anterior to this sulcus, in the frontal lobe, is the precentral gyrus, which is the primary motor cortex. It is involved in the movement of the voluntary skeletal muscular system. Anterior to these areas is the prefrontal cortex, which is responsible for things like personality, consciousness, and short-term memory. Beneath the cerebral cortex are subcortical nuclei, responsible for augmenting the cortical processes. The nuclei of the basal forebrain make acetylcholine, which modulates the overall

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activity of the cortex. The hippocampus and amygdala are medial lobe structures that are responsible for long-term memory and emotions. The basal nuclei are also referred to as the basal ganglia (however, the term is confusing because ganglia are linked to the PNS and not the CNS). The major structures of the basal nuclei are the putamen, caudate, and globus pallidus. The caudate and putamen together are referred to as the striatum. There is a connection between the cerebral cortex and the basal nuclei. In fact, it all goes through the striatum. The direct pathway goes from the striatum to the globus pallidus internal (GPI) segment and the substantia nigra pars reticulata (SNR) and then goes on to the thalamus. The thalamus feeds back to the cortex. The indirect pathway goes from the striatum to the globus pallidus external segment and the subthalamic nucleus (eventually reaching the GPI and the SNR). The two pathways have different activities on the thalamus, causing it to excite (direct pathway) or not excite (indirect pathway) the cortex.

THE DIENCEPHALON The diencephalon means “through brain” and comes from an embryological structure of the same name. It is the connection between the cerebrum and the rest of the nervous system (in almost all cases). The exception to this is the sensation of smell or olfaction, which connects directly to the cerebrum and does not go through the diencephalon. This is a deep structure that includes the thalamus and the hypothalamus. The epithalamus contains the pineal gland, while the subthalamus includes the subthalamic nucleus (part of the basal nuclei). The thalamus is actually a collection of nuclei that send information back and forth between the cerebral cortex and the periphery. It passes all sensory information except for the sense of smell. It also processes the information, deciding which stimuli are important and which are not important. The information for motor control comes from the cerebrum and through the thalamus, which relays information The hypothalamus is below and slightly to the front of the thalamus, which is the other big region of the hypothalamus. This structure is a collection of nuclei that are involved in homeostasis. It is the brain’s part of the autonomic nervous system and the endocrine system.

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It releases hormones that act directly on the anterior pituitary gland. In addition, the hypothalamus is involved in memory and in emotion, making it part of the limbic system.

THE BRAINSTEM The brainstem involves the embryological midbrain and hindbrain. Figure 64 is an illustration of the anatomy of the brainstem:

The midbrain coordinates sensory representations of the visual, somatosensory, and auditory perceptual spaces. The pons is the main connecting structure with the cerebellum. Together the pons and medulla regulate several important cardiovascular and respiratory functions. This part of the brain is where most of the cranial nerves originate and is where there are ascending and descending pathways between the brain and spinal cord.

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The midbrain is a small area between the thalamus and the pons. There are two parts: the tectum and the tegmentum. There is a canal called the cerebral aqueduct, which passes through this area. The tectum is made of four colliculi (little bumps). They process sensation from visual perception, somatosensory perception, and auditory perception; it coordinates and integrates these sensations. The tegmentum contains the cell bodies of the cranial nerves and helps regulate cardiovascular and respiratory function. The pons is the major connecting system between the cerebellum and the brainstem. It also receives information from the forebrain and sends it to the cerebellum. The medulla is made from the myelencephalon in the embryonic brain. It contains white matter that is continued onto the spinal cord. The gray matter of the medulla contains the reticular formation. This is an important structure for sleep and wakefulness.

THE CEREBELLUM The cerebellum is similar in appearance to the cerebral cortex in that it has two halves and has both gyri and sulci. Its main function is to integrate and compare sensory feedback from the spinal cord (the periphery) and the cerebrum. It makes up about ten percent of the total mass of the brain. All motor commands from the cerebrum go, in part, to the pons, where there are nerve fibers connecting this structure to the cerebellum. In addition, sensory information from the periphery is sent, in part, to a nucleus in the medulla called the inferior olive. Fibers from there go to the cerebellum to be compared with descending fibers from the cerebrum. This leads to the coordination of movement, which is the main cerebellar function.

THE VENTRICLES The ventricles are spaces within the brain that contain cerebrospinal fluid that circulates throughout the inside and outside of the central nervous system. It removes metabolic waste from the interstitial fluids of nerve tissue, returning the waste products to the bloodstream. Figure 65 is a depiction of the ventricles of the brain:

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There are four ventricles in the brain, which have been developed from the central canal within the neural tube. The first two are paired and are called lateral ventricles, located in the deep part of the cerebrum. These ventricles are connected to the third ventricle through to openings between these structures, called the interventricular foramina. This third ventricle is located in the space that divides the left and right halves of the diencephalon. This opens into the cerebral aqueduct, which passes through the midbrain and into the fourth ventricle (the space between the cerebellum and the pons/upper medulla). Cerebrospinal fluid is made by a specialized membrane known as a choroid plexus. CSF flows through all four ventricles and exits the fourth ventricle, only to open up into the subarachnoid space. Ependymal cells surround capillaries and filter the blood in the ventricles, putting out CSF on the other side of the choroid plexus membrane. The constituents of CSF include water, electrolytes, and small molecules. Oxygen and carbon dioxide can diffuse across the cell membranes into the CSF where it can diffuse into neural tissue. There are choroid plexuses found in each of the four ventricles. The flow of CSF requires circulation of the cardiovascular system. It flows from the lateral ventricles, through the third and fourth ventricles, picking up more CSF as it flows. About 500 milliliters of CSF is filtered

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each day; it ends up either flowing into the central canal of the spinal cord or up and around the median and lateral apertures into the subarachnoid space. It picks up metabolic waste and cushions the brain and spinal cord. There are arachnoid granulations, which are evaginations of the arachnoid membrane into the dural sinuses; these are where the CSF is reabsorbed into the blood. The blood drains out of the head and neck region via he jugular veins.

BLOOD SUPPLY TO THE BRAIN The aorta has branches that supply the brain. The first branch involves the common carotid arteries, with a second branch happening, leading to the internal carotid arteries. These enter the cranium via the carotid canal. In the back of the head are the vertebral arteries, which pass through the neck via the transverse foramina of the cervical vertebrae. These arteries enter the brain through the foramen magnum. There is a merging of branches of the left and right vertebral artery into the anterior spinal artery, which supplies the anterior part of the spinal cord. The two vertebral arteries merge into the basilar artery that gives branches to the brainstem and cerebellum. Branches of the internal carotids and the basilar artery merge together to make the circle of Willis. This is displayed in figure 66:

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The blood in the brain returns through dural sinuses and veins. There is a large superior sagittal sinus that runs in the longitudinal fissure, collecting waste from the CSF. This drains into a confluence of sinuses, along with the occipital and straight sinuses. These all drain into the transverse sinuses that connect to the sigmoid sinuses—finally leading to the jugular veins.

PROTECTIVE COVERINGS IN THE BRAIN AND SPINAL CORD There are several layers that act as connective tissue coverings that protect the brain. These are called the meninges. The tough, outer layer is the dura mater. It forms a protective sheath over the entire brain and spinal cord. The arachnoid mater is a thin fibrous membrane just beneath the dura mater. Beneath that are the arachnoid trabeculae, which look like a spider web. Adjacent and physically connected to the CNS is the pia mater, the innermost meningeal layer. The dura mater is connected physically to the interior of the cranial bones, there are a couple of infoldings that fit into the large crevasses of the brain itself. Two go into the midline of the cerebrum and cerebellum; one separates the occipital lobe and the cerebellum; and a final one goes to surround the pituitary gland. The arachnoid mater is named as such because it has spider-web trabeculae between this layer and the pia mater. The trabeculae are found in the subarachnoid space, which contains CSF. It is here where the arachnoid granulations exist that drain the CSF into the venous system. This space also provides a liquid cushion for the brain and spinal cord. The CSF is collected here when a sample of this fluid is required. The pia mater is physically adherent to the neural tissue, providing a fluid-impermeable membrane. This is a thin layer that extends into every convolution of the brain and spinal cord. Because the spinal cord doesn’t extend all the way down the lumbar vertebrae, this area of the spinal column is used for a lumbar puncture to collect the CSF for evaluation.

SPINAL CORD STRUCTURE AND FUNCTION The central nervous system consists of both the brain and spinal cord. The brain develops out of expansions of the neural tube, while the spinal cord maintains the tubular structure of the 148

embryological neural tube. There is an anterior median fissure that marks the anterior midline. The posterior median sulcus marks the posterior aspect of the spinal cord. There are dorsal nerve roots on the lateral back aspect of the spinal cord, while there are ventral nerve roots on the lateral front aspect on the spinal cord. In this case, “ventral” means front and “dorsal” means back. In general, the posterior/back region of the spinal cord is where sensory function is, while the anterior/front region of the spinal cord is where the motor function is. The regions of the spinal cord from top to bottom correspond to the level where the spinal nerve exits at each level. There are the cervical, thoracic, and lumbar regions. The spinal cord does not extend all the way down the lumbar region. Instead, there is a bundle of nerves collected beneath the lumbar end of the spinal cord, called the cauda equina. This extends from the upper lumbar vertebral bones to the sacrum. If looked at in cross-section, the gray matter is in the shape of an “H.” The different regions are referred to as horns. The posterior horn participates in sensory processing; the anterior horn participates in motor signaling; the lateral horn, found only in the thoracic, upper lumbar, and sacral regions, makes up the CNS aspect of the sympathetic/autonomic nervous system. Figure 67 is a cross-section of the spinal cord:

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The white matter of the spinal cord is separated into columns. There are ascending tracts and descending tracts. Between the posterior horns of gray matter are the posterior columns, while between the anterior horns are the anterior columns. On the sides of the spinal cord are the lateral columns. These all contain myelinated axons, some of which are ascending and others that are descending fibers.

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KEY TAKEAWAYS •

The CNS consists of the brain and spinal cord. There are nerve cells and neuroglial cells that make up the totality of the nervous system.

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The nerve cell is electrically active, with the propagation of the action potential in just one direction.

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There are excitatory and inhibitory neurotransmitters that allow or don’t allow for propagation of the action potential.

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The brain consists of the cerebrum, cerebellum, diencephalon, and brainstem. The cerebrum is the largest component.

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The ventricular system and subarachnoid space contain cerebrospinal fluid (CSF).

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The spinal cord is tubular and contains ascending and descending tracts leading down to the upper lumbar area.

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QUIZ 1. What aspect of the neuron is usually myelinated? a. Soma b. Ganglion c. Axon d. Dendrite Answer: c. The axon is a process of the neuron that often has a myelin sheath in order to allow faster transmission of the impulse. 2.

What is a collection of axons or nerve fibers called in the central nervous system? a. Nucleus b. Tract c. Ganglion d. Nerve Answer: b. A tract is a collection of axons or nerve fibers within the CNS; the same bundle of axons in the periphery is referred to as a nerve. The same axon can be in a tract and later can be in a nerve.

Which cell type in the CNS will create cerebrospinal fluid (CSF)? a. Microglia b. Oligodendrocytes c. Ependymal cells d. Astrocytes Answer: c. Ependymal cells are those that make the cerebrospinal fluid in the central nervous system.

Which glial cells are also referred to as CNS-resident macrophages? a. Microglia b. Oligodendrocytes 152

c. Ependymal cells d. Astrocytes Answer: a. Microglia are cells that have a different embryological origin and actually stem from white blood cells that become macrophages that are resident in the central nervous system. 5.

Which ion is most closely associated with the presynaptic axon terminal that allows the neurotransmitter-filled vesicles to fuse with the axon terminal membrane? a. Sodium b. Chloride c. Calcium d. Potassium Answer: c. Calcium enters the cell and causes the vesicles containing neurotransmitter to fuse with the axon terminal membrane so that the neurotransmitter can leave the cell into the synaptic cleft.

Which neurotransmitter is always excitatory to the postsynaptic cell? a. Serotonin b. GABA c. Glycine d. Glutamate Answer: d. Glutamate is always an excitatory neurotransmitter because, when it binds to a receptor, it always causes depolarization of the postsynaptic nerve cell.

Which lobe of the cerebrum is most associated with vision? a. Frontal lobe b. Parietal lobe c. Temporal lobe d. Occipital lobe

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Answer: d. The occipital lobe is the lobe of the cerebrum that is most associated with vision, although other lobes participate in this activity. 8.

What part of the deeper cerebrum relays sensory and motor information to and from the cerebral cortex? a. Hypothalamus b. Thalamus c. Medulla d. Pons Answer: b. The thalamus takes information from the cerebrum in order to control motor functions and all sensory information (except for olfaction) goes through the thalamus to the cortex.

What is the major function of the cerebellum of the brain? a. The coordination of eye movements b. The regulation of the sleep-wake cycle c. The control of emotions d. The control of gait and coordination Answer: d. The cerebellum is important in gait and coordination.

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Which part of the brain’s ventricular system is the space between the cerebellum and the pons/upper medulla? a. Lateral ventricles b. Fourth ventricle c. Cerebral aqueduct d. Third ventricle Answer: b. The fourth ventricle is the space between the cerebellum and the pons/upper medulla.

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CHAPTER SEVEN: PERIPHERAL NERVOUS SYSTEM The peripheral nervous system is composed of nerves located outside of the brain and spinal cord. The major somatic sensory and motor nerves are discussed, including the way the major senses are picked up by the body. The cranial nerves, that do not come from the spinal cord, have unique functions, which are discussed. The structure and function of the autonomic nervous system are also covered in this chapter.

BASICS OF THE NERVOUS SYSTEM The nervous system can be divided into three separate areas. These include receiving information from the environment (or sensation), responses to information in the environment (or motor function), and the integration of sensation and motor function, which is usually done by the central nervous system in most cases. Let’s take a look at these three areas: •

Sensation—this is when information about the environment (internal or external) that is detected by sensory receptors. Sensation requires a stimulus, which is a deviation from homeostasis or a new event in the environment. The sensations we think of include taste, smell, sight, touch, and hearing. There are additional sensations that come from inside the body, such as stretch of an abdominal organ wall or a change in the concentration of ions in the bloodstream.

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Response—This activity in response to stimuli perceived by the various sensory structures. The response can be fast and nearly reflexive, such as pulling away from a hot stove, or gradual, such as initiating the action of the smooth muscle of the gastrointestinal tract. There is neural control and responses by the glands, including things like sweat gland output. There are also voluntary and involuntary responses.

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Integration—this is where the stimuli obtained from sensory structures are processed. Stimuli must be received and compared with other stimuli being received as well as memories of past stimuli and experiences. This integration will hopefully lead to an

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appropriate motor response. This happens in the central nervous system because it requires memory and higher cognitive functioning to generate the correct responses. The nervous system has three major parts. The first is the somatic nervous system or SNS. This is responsible for the reception of conscious stimuli, perception, and voluntary motor responses. While these are voluntary, it doesn’t mean that they have to be entirely conscious. A startle response involves the somatic nervous system but rarely does one actually think before startling, which involves movement of skeletal muscles. Other things that are part of the SNS that aren’t truly conscious are things that are done automatically. These happen because of “procedural memory” or the learning of habits. The second part is the autonomic nervous system or ANS. The autonomic nervous system is involuntary in nature and responsible for achieving and maintaining homeostasis. Homeostasis involves the regulation of the internal environment so that it achieves and maintains a steady state. Sensory input can be external or internal but the output is to cardiac and smooth muscles rather than skeletal muscles. Things like the heart, sweat glands, and certain smooth muscle functions of the GI tract are under autonomic control. The third part of the nervous system is the enteric nervous system or ENS. This controls the function of the glandular tissue in the digestive system and most of the smooth muscle function of the digestive tract. This is largely independent and does not rely on the central nervous system. There is some overlap between the functions of the autonomic nervous system and the enteric nervous system.

GLIAL CELLS OF THE PNS There are two types of glial cells found in the PNS. The first is the “satellite cell.” This type of cell is found in the autonomic and sensory ganglia, where they surround the cell bodies of neurons. They are largely supportive cells and are similar to the astrocytes in the central nervous system. In fact, the only difference is that these satellite cells do not establish the blood-brain barrier as is seen in the CNS.

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The second glial cell is referred to as a Schwann cell. This cell makes the myelin sheath around axons in a similar way as oligodendrocytes but with one key difference. Schwann cells wrap around and make myelin for just one axon segment, while the oligodendrocyte reaches out to multiple axon segments at once.

GANGLIA A ganglion is a group of nerve cells, similar to a nucleus, but in the periphery. There can be sensory or autonomic ganglia. The most common type of sensory ganglion is called a dorsal root ganglion. These contain the cell bodies that have axons that become the sensory endings in the periphery, such as the skin. They also have projections that extend upward to the CNS via the dorsal nerve root. The dorsal root ganglion also contains nerve bundle fibers belonging to the dorsal nerve root. Another common sensory ganglion is one of the cranial nerve ganglia. These are like the dorsal root ganglion but are associated with a cranial nerve rather than a spinal nerve. The ganglia reside outside of the skull and send branches out to the cranial nerves. Still another type of ganglion are those associated with the autonomic nervous system. There are sympathetic chain ganglia—a row of identical ganglia that receive input from the lateral horn of the thoracic and upper lumbar spinal cord. Above this chain are the paravertebral ganglia in the cervical region. There are three other autonomic/sympathetic ganglia called the prevertebral ganglia—located anterior to the vertebral column. These are multipolar neurons that make synapses with the spinal cord neurons. Each of these three types of ganglia (chain, paravertebral, and prevertebral) send out axons to the head, neck, thoracic, abdominal, and pelvic cavities to regulate organ homeostasis located in these cavities. Another type of autonomic ganglia is the terminal ganglia. These receive input from the cranial nerves or the sacral spinal nerves, being responsible for the regulation of the parasympathetic nervous system in the head, neck, chest, abdominal, and pelvic cavities. The terminal ganglia oppose the sympathetic ganglia. There are two sets of terminal ganglia—those located in the

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cervical area (that control the cranial nerves, thoracic, and upper abdominal area) and those located in the lower abdominal and pelvic area (receiving input from the sacral area). Together, the different autonomic ganglia receive input that might be sympathetic or parasympathetic from the various organs of the body and together, they send out impulses that oppose each other. The action of the body depends on the relative input from the different sets of ganglia. The terminal ganglia below the head and neck are found together in the wall of the target organ. This cluster is referred to as a plexus. The enteric plexus is an extensive network of axons and nerve cell bodies in the wall of the small and large intestines. This is part of the enteric nervous system, along with two other plexuses: the gastric plexus and the esophageal plexus. Remember that these, being part of the ENS, do not require any input from the CNS in order to function. It should be noted that there are other plexuses that are not affiliated with the autonomic nervous system.

PERIPHERAL NERVES Any bundle of axons in the PNS is referred to as a nerve. These are structurally different than tracts found in the CNS. Nerves, unlike tracts, have connective tissue components as well as blood vessels that act to nourish the nerve tissues. There is a specific structure to a nerve. The tough, fibrous outer connective tissue layer is referred to as the epineurium. Inside the nerve, the nerve fibers are bundled into fascicles. Note the similarity between how a nerve and muscle are organized. Each fascicle is surrounded by more connective tissue, called the perineurium. Each axon is itself surrounded by loose connective tissue known as the endoneurium.

CRANIAL NERVES The cranial nerves are named as such because they are directly attached to the brain rather than the spinal cord. While they predominately affect the sensory and motor function to the head and neck, there are some that are parasympathetic to the chest and abdomen. They are

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labeled I-XII (using Roman numerals). They can be completely sensory, completely motor, or both, including some that control the special senses. As is true also of somatic nerves that originate outside of the vertebral column, nerve cell bodies of sensory nerves (the sensory ganglia) are located outside of the cranium. You will be asked to memorize these cranial nerves and their activities: •

CN I—this is the olfactory nerve, which serves the special sense of smell. Its cell bodies are in the olfactory bulb and the target organ is the olfactory epithelium.

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CN II—this is the optic nerve that controls the special sense of vision. Its cell bodies are in the hypothalamus, the thalamus, and the midbrain. The target organ is the retina, specifically, the retinal ganglion cells.

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CN III—this is the oculomotor nerve. It is motor to the extraocular muscles and autonomic to the pupil. The nucleus is called the oculomotor nucleus and it controls the extraocular muscles and the levator palpebrae superioris and is autonomic to the ciliary ganglion (to control pupillary responses).

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CN IV—this is the trochlear nerve and is strictly motor to the superior oblique muscle. Its cell bodies are in the trochlear nucleus.

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CN V—this is the trigeminal nerve. It privides both sensory and motor functions to the face. There are three trigeminal nuclei in the midbrain, pons, and medulla. It has three branches to the forehead, maxillary area, and the mandibular area. It controls the muscles of mastication.

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CN VI—this is the abducens nerve. It is strictly motor to the lateral rectus muscle and its nucleus is called the abducens nucleus.

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CN VII—this is the facial nerve. It is motor to the face but controls the sense of taste to much of the tongue. It also controls part of salivation. It has three nuclei: the facial nucleus, the solitary nucleus, and the superior salivatory nucleus. It controls the movement of nearly all the facial muscles. The geniculate ganglion and the pterygopalatine ganglion are the autonomic ganglia of this nerve.

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CN VIII—this is the auditory or vestibulocochlear nerve. It controls the special senses of hearing and balance. Its nuclei are the cochlear nucleus and (in the cerebellum) the vestibular nucleus. Hearing sensation involves the spiral ganglion, while balance sensation involves the vestibular ganglion.

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CN IX—this is the glossopharyngeal nerve. It is both motor to the throat and has the special sensation of taste to a part of the tongue. It also helps in salivation. Its nuclei are the solitary nucleus, the nucleus ambiguus, and the inferior salivatory nucleus. The target organs are the pharyngeal muscles, the geniculate ganglion, and the otic ganglion.

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CN X—this is the vagus nerve. It is a motor and a sensory nerve, being autonomic to the viscera. Its nucleus is in the medulla. The target organs are the terminal ganglia for the heart and small intestines. It is also responsible for the gag reflex.

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CN XI—this is the spinal accessory nerve. It is entirely motor to the head and neck. The origin is in the spinal accessory nucleus and the target organs are the neck muscles.

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CN XII—this is the hypoglossal nerve. It is entirely motor to the lower throat. Its nucleus is called the hypoglossal nucleus and the target organs are the muscles of the larynx and lower pharynx.

The cranial nerves that are related somewhat to the autonomic nervous system include the oculomotor nerve (the pupillary reflex), the facial nerve (salivation), and the glossopharyngeal nerve (salivation). The vagus nerve is entirely autonomic, targeting the autonomic ganglia in the upper abdomen and thorax.

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Figure 68 shows the origin and function of the twelve cranial nerves:

SPINAL NERVES Some nerves are not connected at all to the brain but are instead connected to the spinal cord. This is a more regular arrangement, with a nerve exiting between each of the vertebrae. All of these nerves combine both sensation and motor function, with axons that separate into two nerve roots. The sensory component involves axons that enter the spinal cord via the dorsal nerve root, while the somatic and autonomic motor nerve leave the spinal cord as the ventral nerve root.

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There are 31 spinal nerves, labeled according to the vertebral level. There are eight pairs of cervical spinal nerves, labeled C1 to C8, 12 pairs of thoracic spinal nerves, labeled T1 to T12, five pairs of lumbar spinal nerves, labeled L1 to L5, five pairs of sacral nerves, labeled S1 to S5, and a single pair of coccygeal nerves. The first spinal nerve, C1, exits between the occipital bone and the first cervical vertebra; the others follow, exiting just above the vertebra it is named after. The exception is C8, which emerges between the seventh cervical vertebra and the first thoracic vertebra. The actual nerves in the periphery involve the reorganization of axons in the spinal nerves to make a nerve that follows a specific course. Axons from different spinal nerves will come together to form a systemic nerve. They do this reorganization at four different areas along the spinal cord in places called a “nerve plexus.” There are no cell bodies in nerve plexuses—only axons that are getting reorganized. •

The cervical plexus incorporates axons from the C1-C5 nerve root level to make head/neck nerves and the phrenic nerve, supplying the diaphragm.

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The brachial plexus incorporates C4-T1 to make the nerves of the arms. Two large branches are the radial nerve and the axillary nerve. There are two sub-branches to the radial nerve: the ulnar and median nerves. Figure 69 shows the brachial plexus:

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The lumbar plexus comes from all the lumbar spinal nerves to make nerves to the pelvis and anterior leg. The femoral and saphenous nerves come from this plexus.

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The sacral plexus comes from L4, L5, and the sacral nerves S1-S4. The sciatic nerve is the major nerve that comes from this and it innervates the posterior leg.

The thoracic spinal nerves T2 through T11 do not participate in a plexus but give rise to the intercostal nerves, each of which travels along and between the ribs.

SENSORY RECEPTORS The purpose of sensory receptors is to take stimuli from the external or internal environment and send the appropriate signal to the central nervous system for processing. Most sensory receptors do not act in isolation but their signals get integrated with other sensations to make a complete picture of the situation. The way this works is that a specific stimulus changes the cell membrane potential of a sensory nerve cell so that the signal can traverse the cell and will eventually reach the CNS. This leads to a conscious perception and the possibility of a motor response. Ultimately, the sensation leads to a perception (in the CNS). There are different types of receptor cells that respond to different stimulus types. Receptors can be identified by three different criteria, including their position, the cell type, and the function. Let’s first look at structural cell types. There are three classifications of receptor types that receive a stimulus: •

Free nerve ending type—this is when the dendrites are directly imbedded in a type of tissue that receives a particular sensation. Pain and temperature receptors in the skin are free ending types of receptors.

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Encapsulated ending—this is when the nerve ending is encapsulated in connective tissue. This causes an enhancement of the nerve cell’s sensitivity. The lamellated corpuscles we’ve talked about already in the dermis are of this type of receptor; they respond to touch and pressure.

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Specialized receptor cell—this is a cell that has distinct structural components designed to interpret a certain stimulus. A photoreceptor in the retina is an example of this kind of receptor cell.

Receptors can also be classified according to their location in relation to the stimulus they receive. There are exteroceptors that are located near a stimulus in the external environment, such as the sensory receptors in the skin. On the other hand, an interceptor is one that receives a stimulus from an internal organ or tissue. These include those that sense a person’s blood pressure in the carotid sinus and aorta. A proprioceptor is a third type that is located near a moving part of the body so that it can interpret the positions of the tissues as they move during body motion (to keep balance, etc.). A third type of receptor classification is by how the receptor changes the stimulus into a change in membrane potential. There are three types of stimuli: •

Ions and macromolecules—the cross the membrane of the cell and affect a signal change

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Physical stimuli—these physically stimulate the cell membrane, causing an action potential

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Electromagnetic radiation—this is when UV light stimulates photoreceptors (although there are similar receptors, like magnetoreceptors in birds, that humans don’t have)

Receptor cells can also be categorized on the basis of the stimuli they respond to. These include the following: •

Chemoreceptor—these interpret chemical stimuli like smell or taste

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Osmoreceptor—these respond to certain concentrations of solutes

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Nociceptor—these receive the sense of pain by sensing chemicals from damaged tissue

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Mechanoreceptor—these respond to physical stimuli like pressure, vibration, and body position

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Thermoreceptor—these can respond to either heat or cold

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There are actually a lot of different sensations besides vision, hearing, touch, smell, and taste. Balance is a sensation as well, involved in what’s known as proprioception (the knowledge of where the body is in space). Touch has several subdivisions, including hair-follicle position, stretch reception, vibration sense, and pressure sensation. Temperature and pain sensations are also separate senses. Depending on divisions and subdivisions used, there can be as many as seventeen different sensory modalities. Let’s look at a few of the major ones. Taste Taste is also referred to as gustation. There are several different basic tastes: salty, sweet, bitter, sour, and umami (savory). A sixth sense of the taste of fats may also be present. The tongue is where taste is perceived. There are papillae (raised bumps) that contain gustatory abilities. The four types of papillae are circumvallate, filiform, folate, and fungiform (according to appearance). Within the taste buds are chemoreceptors called gustatory receptor cells. They release neurotransmitters based on the amount of chemicals in the food being tasted. The facial, glossopharyngeal, and vagus cranial nerves are all associated with taste neurotransmission. Salt taste depends on the concentration of sodium in the saliva. Sour taste depends on the concentration of hydrogen ions in the saliva. In both cases, the ions enter the cell, resulting in depolarization of the cell. The other tastes depend not on an ion concentration but on the reactivity of a molecule with a G protein-coupled receptor (intramembranous protein reception). Sweet sensation depends on the glucose concentration (and artificial sweeteners). Bitter taste is also a G protein-coupled receptor sensation but there are a great many bittertasting molecules. Some will depolarize the cell, while others will hyperpolarize the cell. Alkaloids are found in many substances (like coffee, beer hops, aspirin, tea, and wine tannins). These alkaloids have an evolutionary advantage to the plant containing them because they resist microbes and aren’t eaten much by herbivores. Bitter receptors are found in the back of the tongue so they can initiate the gag reflex for potentially poisonous foods. Umami is another G-protein coupled receptor sensation that is triggered by a specific molecule: L-glutamate. This basically means that protein-rich foods containing this amino acid are

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perceived as savory and have an umami taste. Figure 70 shows a map of where the receptions of the various taste sensations are mainly located on the tongue:

SMELL The sense of smell is also called olfaction. This involves chemoreceptors in the olfactory epithelium of the upper nasal cavity. The epithelium contains bipolar sensory nerve cells that have dendrites extending into the mucosal lining of the nose. Airborne molecules dissolve into the mucosa and bind to proteins that transport the molecules to the olfactory nerve cell dendrites. The receptors in the nerve cell are G protein-coupled receptors, ultimately causing an action potential. The axon of the olfactory neuron extends upward from the basal surface of the epithelium, through the cribriform plate, and into the brain. The axons together from an olfactory tract that connects to the olfactory bulb in the frontal lobe. From there, the nerve impulses go to many parts of the brain, including those responsible for long-term memory of smells and emotional responses. This is why smells often trigger specific emotional responses. Smell isn’t filtered by the thalamus, making it more powerful in evoking emotion. Figure 71 shows what the process of smell looks like in the upper nose:

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HEARING This is also referred to as audition. It involves the transduction of sound waves into a neural signal using internal structures of the ear. The auricle is basically the outer ear, which directs sound waves toward the auditory canal. The external auditory meatus is located in the temporal bone; at the end of it, sound strikes the tympanic membrane. Together, these three structures are called the external ear. The middle ear is the space behind the tympanic membrane that contains three small bones: the malleus, incus, and stapes. They articulate with one another and send the signal to the inner ear. In the inner ear, the sound waves will be translated into a neural signal. Air pressure is equilibrated in the middle ear by the Eustachian tube that extends from the middle ear to the pharynx. Figure 72 illustrates the ear anatomy:

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The inner ear is described as a bony labyrinth—a series of canals within the temporal bone consisting of two regions: the vestibule and the cochlea. The vestibule is responsible for balance, while the cochlea is responsible for hearing. They have two separate nerve bundles that together form the vestibulocochlear nerve. The cochlea has the cell bodies of the spiral ganglia, which detect sound and transmit it to the brain. There is fluid in the cochlea that runs in a wave motion that is consistent with the frequency of the sound wave. There are organs of Corti in the cochlea that contain hair cells, which themselves contain stereocilia (microvilli) that bend in response to sound. This bending of stereocilia will trigger ion channels to open or close in the cell, causing depolarization of the cell. Different hair cells are activated according to the sound’s frequency. Different frequencies of sound will change the hair cells on different parts of the cochlea.

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BALANCE This is referred to as equilibrium, which involves mechanoreception in the vestibule. There are hair cells with similar stereocilia as just described located in the vestibule that sense motion, head position, and head movement. Head position is detected by the utricle and saccule parts of the vestibule, while movement Is detected by the semicircular canals. There is a vestibular ganglion (nerve cell body collection) in the vestibule that sends information about balance to parts of the brainstem and cerebellum along the vestibulocochlear nerve. The stereocilia of the hair cells extend into a viscous gel known as the otolithic membrane. On the surface of this membrane are otoliths, which are small stones made from calcium carbonate. The otoliths move the otolithic membrane in certain positions of the head, bending the stereocilia and resulting in hyperpolarization or depolarization of the hair cells. This results in the detection of head position.

TOUCH This is referred to as somatosensation and is a general sense rather than a special sense (as is the case with the other senses). Somatosensation involves things like kinesthesia, proprioception, pain, temperature, itch, tickle, light touch, vibration, and pressure. There is no special organ associated with these sensations—only multiple receptors located all over the body. These receptors can be located in the skin, tendons, muscles, ligaments, joint capsules, and in visceral organ walls. The free nerve ending sensations are the thermoreceptors (temperature) and nociceptors (pain). Some thermoreceptors are particularly sensitive to heat, while others are only sensitive to cold. The sensations of heat and cold are relative to the body’s own temperature. Nociception is the detection of possibly damaging stimuli. They respond to thermal, chemical, or mechanical stimuli. Chemicals in damaged tissue will activate nociceptors. Mechanoreceptors known as Merkel cells will detect vibration sense. As you remember, they are located in the stratum basale in the epidermis. Deeper in the skin are lamellated corpuscles (also called Pacinian corpuscles), which detect deep pressure and some vibration. Meissner corpuscles are encapsulated nerve endings that detect light touch. Skin stretch is detected by

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stretch receptors called bulbous corpuscles (Ruffini corpuscles). Plexuses of nerves around hair follicles will detect hair movement. Stretch receptors and other somatosensory receptors are also found in joints and muscles. In skeletal muscle, the stretch receptor that does this is called a muscle spindle. The same thing in tendons is called a Golgi tendon organ. There are also bulbous corpuscles seen in joint capsules that measure the amount of stretch inside the joint itself.

VISION Vision is a special sense that relies on the transduction of light stimuli received through the eyes. There are two eyes inside bony orbits that result in binocular vision. The eyelids are present to help protect the eye from abrasions and the eyelashes help filter dust away from the eyes. The palpebral conjunctiva is the inner lining of the eyelids. It extends back onto the white part of the eye (which is called the sclera). Figure 73 illustrates the anatomy of the eye:

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Tears are created by the lacrimal gland, located beneath the lateral aspect of the nose. The tears flow from the lacrimal duct in the medial eye to wash away foreign debris from the surface of the eye. There are six extraocular muscles that control the eye movements. They start in various bones of the orbit and attach to the eyeball itself. There is the superior rectus, inferior rectus, medial rectus, and lateral rectus on their corresponding part of the eyeball. In addition, the superior oblique muscle rotates the eye in a medial direction and the inferior oblique muscle rotates the eye in a lateral direction. The only other muscle in the orbit is the levator palpebrae superioris, which elevates and retracts the upper lid. The trochlear, oculomotor, and abducens nerves all help to rotate the eye in all directions. The eye itself is hollow and made from three layers of tissue. The outermost layers include either the cornea (clear in nature) and the sclera (white in nature). The cornea is transparent which allows light enter the eye. The middle layer of the eye is called the vascular tunic. It consists of the choroid, the ciliary body, and the iris. The choroid provides the blood supply to the eyeball; the ciliary body is a muscular structure attached to the lens by fibers called zonule fibers. Together, these bend the lens so that it can focus light on the retina at the back of the eye. The iris is a smooth muscle and is the colored part of the eye. It can open or close to make the pupil smaller or bigger. The innermost layer of the eye is the retina, also called the neural tunic. It contains the nerve fibers necessary for vision. There are two sections to the eyeball: the anterior and posterior cavity. The anterior portion is the space between the cornea and lens; it includes the iris and the ciliary body. It is filled with a thin watery fluid known as the aqueous humor. The posterior cavity is the larger part behind the lens, containing the vitreous humor, which is thicker in nature. There are several layers within the retina. The photoreceptors (also called the rods and cones) will change their transmembrane potential according to light stimuli. Neurotransmitters are then released to affect cells of the outer synaptic layer (the bipolar cells). These bipolar cells connect each photoreceptor to a retinal ganglion cell (RGC), located in the inner synaptic layer.

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The axons of these RGCs all collect at the optic disc and leave the eye as the optic nerve. There are no photoreceptors in the optic disc, creating a “blind spot”. The exact center of the retina is called the fovea. This part contains only photoreceptors and lacks the overlying blood vessels and other cell layers that cover the photoreceptors in other areas. This makes this part of the retina have the best visual acuity. Each photoreceptor is connected to just one RCG so that the acuity can be remarkably sharp. Toward the edges of the retina there can be 50 photoreceptors to one RCG, which reduces the sharpness significantly. The light that reaches the retina causes chemical changes to pigmented molecules in the photoreceptors, which activate the RCGs. There is an inner segment in a photoreceptor cell that contains the nucleus and major organelles and an outer segment, which is specialized for photoreception. The rods contain a stack of discs that have rhodopsin in them (which are photosensitive). The cones have infoldings that contain photosensitive pigments. There are three photopigments in the cones (called opsins), which are each sensitive to a different wavelength of light. The visual stimulus reaching a photoreceptor causes a change in the photopigment molecule, leading to an action potential in the photoreceptor cell. These allow for the perception of light between 380 nm and 720 nm in wavelength. The opsin pigments have a cofactor called retinal (a hydrocarbon molecule related to vitamin A). The light hits the retinal and changes its biochemical appearance—a process known as photoisomerization. This change in retinal along with the opsin proteins will result in the activation of a G protein which is a transmembrane protein that can change the membrane potential of the cell. The photoisomerization process gets changed back via enzymatic processes. Rods are more sensitive in low-light conditions, whereas cones, which respond to red, green, and blue wavelengths, are more active in bright light conditions. Rods are the photoreceptors that are active in low light and the cones are more sensitive in bright light conditions. The brain can visualize all the different colors by comparing the activity of the different photopigments in the cones. Low light vision tends to be relatively colorless because the rods are not colorsensitive.

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CRANIAL VERSUS SOMATIC NERVES Somatic sensory nerves contain axons from different sensory receptors. These are called afferent fibers. Within the same nerve are efferent “motor” or outgoing nerves. The nerve splits at the spinal cord into dorsal (sensory) roots and ventral (motor and autonomic) roots. Spinal nerves, you should know, involve contralateral innervation. This means that the right side of the body is connected to the left brain, while the left side of the body is connected to the right brain. This is not true of cranial nerves. These are mostly ipsilateral, meaning the nerve fibers do not cross over. In the spinal cord, there are tracts that are specifically for the transfer of sensory information to the brain. These are the dorsal column, the medial lemniscus, and the spinothalamic tract. The fasciculus gracilis is the part of the dorsal column that contains axons from the legs and lower body, while the fasciculus cuneatus contains axons from the upper body and arms. Each of these axons end in the medulla of the brain, sending another neuron back up toward the rest of the brain. Shortly after this, the crossing over or “decussation” happens. The axons then go up to the thalamus. The third neuron starts in the thalamus and ends in the postcentral gyrus of the cerebral cortex. This means that three nerves are necessary for sensory information processing. This controls light touch and proprioception. The spinothalamic tract is responsible for pain and temperature sensations. Everything happens the same as with the dorsal tracts except that they decussate in the spinal cord at the level in which they first enter the spinal cord. The trigeminal pathway (a cranial nerve pathway) also has three nerves involved in controlling the sensation but there are different places for the nerves to go: the second nerve starts in the spinal trigeminal nucleus (in the medulla), the chief sensory nucleus (in the pons) or in the mesencephalic nucleus in the midbrain. There is decussation after that, with ascension into the thalamus and later, the cerebrum. As mentioned, not all cranial nerves have ipsilateral communication with the brain. Vision, and the optic nerve, is one of these. Axons from the medial side of the retina will decussate, while the axons of the lateral side of the retina do not decussate. In some cases, the peripheral vision

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can be lost when there is a pituitary tumor that presses on the crossed-over nerves in the optic chiasm.

GENERATING MOTOR RESPONSES It takes cerebral input from the prefrontal (motor) cortex in order to initiate movement. There are two important secondary motor cortices: the prefrontal cortex and the supplemental motor cortex. The premotor cortex is more to the side of the brain, while the supplemental motor cortex is on the top and middle of the brain. The premotor area is concerned with posture and core muscles, while the supplemental motor cortex is responsible for planned movements. These work with the primary motor cortex to generate movement. The neurons in the motor cortex are called Betz cells. They send axons down the corticospinal tract (to the spinal cord) and the corticobulbar tract (for cranial nerve function). The axons of the corticobulbar tract are ipsilateral (they do not cross over); the axons of the corticospinal tract do cross over, however. The point of crossover in the medulla is called the pyramids. Those that go down the spinal cord go down the lateral corticospinal tract. They control the muscles of the limbs. The axons that control trunk muscles go down the anterior corticospinal tract. They do not decussate until they reach the level they are intended to exit out of the spinal cord. Some do not cross over so that posture, which requires coordination of both sides of the body, is controlled by nerves from both sides of the brain.

AUTONOMIC NERVOUS SYSTEM The autonomic nervous system controls contraction of the cardiac and smooth muscle, as well as glandular tissue. The responses are involuntary and are responsible mainly for homeostasis. There are two divisions to the autonomic nervous system: the sympathetic and parasympathetic division. The sympathetic nervous system is linked to the “fight-or-flight response,” while the parasympathetic nervous system is linked to the “rest and digest response”. Homeostasis is maintined through the balance of these two systems.

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The sympathetic division has connections to the brain via the thoracolumbar system (the thoracic and upper lumbar spinal cord). There is a sympathetic chain ganglion on each level of the vertebral column in these regions for a total of 23 sympathetic ganglia on each side of the spinal cord. A nerve can project directly to a target organ from here (as is the case with the adrenal medulla innervation). In other cases, there is not a direct connection so there needs to be other ganglia to send the signal along. There are paravertebral and prevertebral ganglia that participate in this process. In such cases, there is a preganglionic and postganglionic fiber (that goes to the target organ). Postganglionic fibers are much longer than preganglionic fibers. The sympathetic nervous system does several things. It increases the heart rate, increases the breathing rate, increases the blood flow to the extremities, decreases the blood flow to the digestive system, and stimulates sweat gland secretion. The parasympathetic division has its central neurons on either side of the thoracolumbar region. There are also neurons near the brainstem and the sacrum. The biggest difference is that the preganglionic fibers are long and he postganglionic fibers are short. The ganglia are located near the target organs, often called intramural ganglia. The effect of this system is opposite in general to what the sympathetic nervous system does. The neurotransmitters involved in the sympathetic nervous system can be acetylcholine or norepinephrine. As mentioned before, there are nicotinic and muscarinic receptors in the acetylcholine system. Both receptors bind acetylcholine but are structurally different from one another. The norepinephrine or adrenergic system has alpha-adrenergic receptors and betaadrenergic receptors. Both are G protein-coupled receptors. There are three subtypes of alpha receptors and two types of beta receptors. All preganglionic fibers secrete acetylcholine, while the postganglionic parasympathetic fibers also secrete acetylcholine. Postganglionic sympathetic fibers mostly secrete norepinephrine, except for those that go to sweat glands and to blood vessels in skeletal muscles. (These secrete acetylcholine). There is a division of the autonomic nervous system that is the enteric nervous system. This involves myenteric plexuses in the wall of the digestive tract organs that will directly affect digestion. There is an autonomic reflex so that, for example, when the stretch receptors in the

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stomach are activated by eating, motility is stimulated to try and digest/remove food from the stomach. It does not require CNS input. Homeostasis is achieved because all the target organs have innervation by both the parasympathetic and sympathetic nervous systems. The target cells in the target organ have both cholinergic (parasympathetic) and adrenergic (sympathetic) receptors. If more norepinephrine is released, it will cause sympathetic activity to occur; if more acetylcholine is released, it will cause parasympathetic activity to occur. Key differences are the sweat glands, which don’t have any parasympathetic input, and the skeletal muscle blood vessels, that have acetylcholine released by both the sympathetic and parasympathetic nervous systems. This balance between the two systems is called the autonomic tone.

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KEY TAKEAWAYS •

The peripheral nervous system includes everything in the nervous system outside of the brain and spinal cord.

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There are motor nerve axons and sensory nerve axons that, for the most part, travel in the same nerve bundle until they reach the spinal cord, when they divide into the ventral and dorsal horn.

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The cranial nerves (twelve of them) attach directly to the brain and brainstem and not to the spinal cord.

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The sensory receptors involve special senses (like taste, vision, and hearing) and somatic sensation (like touch, vibration, and temperature sensation).

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The autonomic nervous system has two branches: the parasympathetic and sympathetic nervous divisions.

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QUIZ 1. Which of the following is most similar to the satellite cell? a. Oligodendrocyte b. Astrocyte c. Ependymal cell d. Microglia Answer: b. The satellite cell is a supportive cell that is similar to the astrocyte in the central nervous system. 2.

Which is the central nervous system equivalent to the Schwann cell in the PNS? a. Oligodendrocyte b. Astrocyte c. Ependymal cell d. Microglia Answer: a. The oligodendrocyte and the Schwann cell both make the myelin sheath, making them roughly equivalent cell types.

What is the bundle of nerve fibers within a nerve that the nerve is divided into? a. Epineurium b. Fascicle c. Perineurium d. Endoneurium Answer: b. A fascicle is a bundle of axons within a nerve fiber; multiple fascicles together make the whole nerve.

Which cranial nerve is entirely autonomic in nature? a. Oculomotor b. Facial c. Glossopharyngeal 178

d. Vagus Answer: d. Each of these partially contribute to the autonomic nervous system; however, the vagus nerve is entirely autonomic, sending signals to autonomic ganglia in the chest and upper abdominal area. 5.

Which cranial nerve is not entirely motor in nature? a. Abducens b. Trochlear c. Oculomotor d. Hypoglossal Answer: c. The oculomotor innervates four of the extraocular muscles and the levator palpebrae muscle but it is autonomic to the pupil, where it controls the pupillary response.

Which cranial nerve supplies the most external ocular nerves? a. Abducens b. Optic c. Trochlear d. Oculomotor Answer: d. The oculomotor nerve supplies four of the six external ocular muscles. The trochlear and abducens nerve each supply one external ocular muscle.

What receptor type best describes a photoreceptor cell type? a. Mechanical transduction receptor b. Encapsulated cell receptor c. Specialized receptor cell d. Free nerve ending receptor Answer: c. The photoreceptor is a specialized receptor cell that uses UV light to cause a change in the cell membrane action potential. 179

What type of receptor receives the sensation of pain? a. Nociceptor b. Chemoreceptor c. Mechanoreceptor d. Osmoreceptor Answer: a. A nociceptor responds to chemicals released by damaged tissues and interpret this as a sensation of pain.

Which ear structure is not responsible for hearing? a. Vestibule b. Cochlea c. Malleus d. Stapes Answer: a. The vestibule is actually responsible for balance in the ear and is not involved in the formation of sound through hearing, while the other structures participate in the hearing process.

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Which specialized skin structure detects stretch sensation? a. Meissner corpuscles b. Pacinian corpuscles c. Bulbous corpuscles d. Merkel cells Answer: c. It is the bulbous corpuscles in the skin or other tissue that detects stretch of the tissues. The others are types of mechanoreceptors that detect other things, like touch and vibration sense. Bulbous corpuscles are also called Ruffini corpuscles.

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CHAPTER EIGHT: ENDOCRINE SYSTEM The chapter discusses the endocrine system and the hormones and their interactions throughout the body. There are numerous “endocrine” organs within the brain and throughout the rest of the body. The hypothalamus, the pituitary gland, and the pineal gland are all located near or within the brain itself. The other endocrine glands covered are the adrenal, the thyroid, the parathyroid glands, and the endocrine portion of the pancreas.

HORMONES A hormone is any molecule released within the body that acts on a distant target organ. There are receptors on the target organ cells that respond only to the hormone, causing an effect on the target cells. Hormones are primarily involved in homeostasis, the regulation of human reproduction, growth and development of the tissues of the body, fluid and electrolyte balance, the initiation of sleep, and metabolism. A summary of the major hormones and their effect is as follows: •

Growth hormone (GH)—this is a protein-based hormone that is secreted by the anterior pituitary gland and promotes the growth of the body’s tissues.

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Prolactin (PRL)—this is a peptide hormone secreted by the anterior pituitary gland. It promotes the production of milk.

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Thyroid stimulating hormone (TSH)—this is a glycoprotein hormone secreted by the anterior pituitary gland. It stimulates the release of thyroid hormone.

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Adrenocorticotropic hormone (ACTH)—this is a peptide hormone secreted by the anterior pituitary gland. It stimulates hormone release by the adrenal cortex.

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Follicle stimulating hormone (FSH)—this is a glycoprotein hormone secreted by the anterior pituitary gland. It stimulates gamete (sperm and egg) production.

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Luteinizing hormone (LH)—this is a glycoprotein hormone secreted by the anterior pituitary gland. It stimulates androgen production by the gonads and triggers ovulation in females.

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Antidiuretic hormone (ADH)—it is a peptide protein secreted by the posterior pituitary gland. It stimulates water reabsorption by the kidneys.

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Oxytocin—this is a peptide hormone secreted by the posterior pituitary gland. It stimulates uterine contractions during childbirth.

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Thyroxine and triiodothyronine—these are amine hormones secreted by the thyroid gland. They stimulate the basal metabolic rate in the cells of the body.

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Calcitonin—this is a peptide hormone secreted by the thyroid gland. It reduces blood calcium levels.

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Parathyroid hormone (PTH)—this is a peptide hormone secreted by the parathyroid gland that increases calcium ion levels in the bloodstream.

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Aldosterone—this is a steroid hormone secreted by the adrenal cortex. It increases blood sodium levels.

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Cortisol—this is a steroid hormone that, along with corticosterone and cortisone, is secreted by the adrenal cortex. The function is to increase blood glucose levels.

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Epinephrine and norepinephrine—these are amine hormones that are secreted by the adrenal medulla and stimulate the fight-or-flight response.

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Melatonin—this is an amine hormone secreted by the pineal gland. It regulates the sleep cycles.

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Insulin—this is a protein hormone secreted by the pancreas. It reduces blood glucose levels in response to high glucose levels.

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Glucagon—this is a protein hormone secreted by the pancreas. It increases the blood glucose levels in response to low glucose levels.

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Testosterone—this is secreted by the testes and is a steroid hormone. It stimulates the development of the male secondary sex characteristics and sperm production.

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Estrogen and progesterone—these are steroid hormones that stimulate the development of female secondary sex characteristics and manage the menstrual cycle and pregnancy.

HORMONE TYPES There are several different hormone classifications: steroid hormones, peptide hormones, amine hormones, protein hormones, and glycopeptide hormones. The amine hormone includes norepinephrine, which is a modified amino acid. The oxytocin hormone is an example of a peptide hormone (which is a short amino acid molecule). Growth hormone is a protein hormone (which is a long chain of amino acids). Testosterone is an example of a steroid hormone. Amine hormones are modified amino acids, with removal of the carboxyl group. These are synthesized from tryptophan or tyrosine. An example of a tryptophan-based hormone is melatonin, secreted by the pineal gland. Tyrosine derivatives include the thyroid hormones, epinephrine, norepinephrine, and dopamine. Dopamine is an inhibitory neurotransmitter/hormone that blocks the release of some anterior pituitary hormones. Peptide and protein hormones are all chains of amino acids. The difference between these is the length of the amino acid chain. Both are synthesized by the usual DNA/mRNA and ribosomal protein synthesis channels. Examples of peptide hormones include antidiuretic hormone (ADH) and atrial-natriuretic peptide (which decreases blood pressure and is made by the heart). Some protein-based hormones include growth hormone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Both FSH and LH are called glycoproteins because they have added carbohydrates attached to the protein. Steroid hormones are lipid-derived, made from cholesterol. These include testosterone, estrogen, progesterone, cortisol, and aldosterone. These are not water-soluble so they need to travel via a transport protein. As a result these types of hormones are longer-lasting than 183

amine hormones. The half-life of a steroid hormone is 60-90 minutes, while the half-life of amine hormones is about one minute.

HORMONE PATHWAYS AND ACTIONS Hormones are usually passed via the bloodstream, where they are received by a hormone receptor, which is located within the cell membrane or inside the cell itself. The message gets processed, resulting in a change in the metabolic processes of the target cell. A similar receptor might be located on different body tissues, resulting in different responses initiated by the same hormone. The action on the cell can involve protein synthesis, the activation or deactivation of enzymes, altered cell growth and mitosis, alteration in cell membrane permeability, or the secretion of products. Intracellular hormone receptors are located within the cell itself. This means that the hormone needs to pass through the cell membrane in order to have activity. Steroid hormones act this way because they are lipid soluble and easily pass through the cell membrane. Thyroid hormones, which are also lipid-soluble can enter the cell to act on intracellular hormone receptors. Figure 74 describes the activity of a steroid hormone on a target cell:

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The steroid hormone binds to a receptor in the cytosol or nucleus. This hormone-receptor complex moves toward the cell’s DNA and attaches to it. Thyroid hormones bind directly to receptors already in connection with DNA. It triggers the mRNA production and activates the ribosomes to make new proteins. Water-soluble or hydrophilic hormones cannot diffuse across the cell membrane. For this reason, they must pass the message to a receptor located at the surface of the cell. All amine hormones (except thyroxine and triiodothyronine) require this type of receptor. The hormone becomes the first messenger, triggering a second messenger that acts within the cell. In most cases, the second messenger is cyclic AMP or cAMP. It requires a G protein-receptor that binds the hormone and activates adenylyl cyclase, which converts ATP to cAMP. This cAMP activates protein kinase (an enzyme) that initiates a cascade called a “phosphorylation cascade,” which causes an effect on the cell. Figure 75 depicts what this looks like:

The hormones that use this second messenger include calcitonin, glucagon, and TSH. The entire process of the phosphorylation cascade is very efficient, resulting in a wide variety of cellular responses. The lifespan of cAMP is very short, however, because it is degraded and deactivated by phosphodiesterase (another enzyme). There are certain hormones that will decrease the

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cAMP levels when they bind to the cell membrane, such as somatostatin (growth hormone inhibiting hormone), which blocks GH release by the pituitary gland. While cAMP is the most common second messenger, there can be other second messengers. One involves calcium ions; it makes use of phospholipase C (PLC), which acts like adenylyl cyclase, which separates a membrane-bound phospholipid into diacylglycerol (DAG) and inositol triphosphate (IP3). The first (DAG) initiates the phosphorylation cascade, while IP3 causes an increase in calcium release from the smooth endoplasmic reticulum. The calcium acts as a second messenger and causes several enzymatic changes to occur in the cell. There are certain factors that affect the hormone responses to a cell. When there are high levels of circulating hormones in the bloodstream, the target cells will decrease the numbers of receptors on the surface—a process known as downregulation. The cells will become less active. On the other hand, with chronically low levels of hormones in the bloodstream, there will be upregulation of the receptors. Two or more hormones can interact with one another in several different ways. The three most common ways for hormones to interact with one another include the following: •

Permissive interaction—this is when one hormone allows another hormone to act. This is the case with thyroid and reproductive hormones.

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Synergistic interaction—two similar hormones will have an amplified response. This is the case with a combination of FSH and estrogen, both necessary for egg maturation.

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Antagonistic interaction—this is when two hormones oppose each other. This is the case with glucagon and insulin, which are both made by the pituitary gland.

REGULATION OF HORMONE SECRETION There needs to be tight control of hormone levels in the body. This is done by the activity of feedback loops that operate in most hormone secretion systems. There are a few positive feedback loops that increase the amount of the hormone. An example of this is oxytocin, which

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increases in childbirth as the cervix stretches in labor. This triggers an increasing amount of oxytocin and more intense contractions that only decrease after childbirth has occurred. More commonly, there are negative feedback loops. These occur after the release of the hormone causes a negative feedback onto another endocrine organ that inhibits the further release of the hormone. There are several examples of this, such as the feedback loop involving thyroid hormones and glucocorticoids. The feedback endocrine organs involve both the pituitary gland and the hypothalamus. Figure 76 involves the negative feedback loop in thyroid hormone secretion:

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PITUITARY GLAND AND HYPOTHALAMUS Some call the pituitary gland the “master gland” because it secretes many important endocrine hormones, while others give this title to the hypothalamus. Regardless, the combination of the two glands, which are in close proximity to one another, have a commanding presence over the rest of the endocrine system. The hypothalamus is in the diencephalon of the brain, just beneath and in front of the thalamus. It has neural and endocrine activity. It is connected to the pituitary gland by a stalk called the infundibulum, from which the pituitary gland hangs. There are two lobes to the pituitary gland: an anterior and posterior lobe. The posterior lobe is made from neural tissue, while the anterior lobe is made from endocrine tissue. Almost all of the pituitary hormones are secreted by the anterior lobe of the gland, except for oxytocin and antidiuretic hormone (ADH), which are secreted by the posterior lobe, and melanocyte stimulating hormone (MSH), which is secreted in the intermediate zone of the gland. Figure 77 shows the functions of the pituitary gland:

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POSTERIOR PITUITARY GLAND The posterior pituitary gland is actually neural tissue—an extension of the neurons of both the paraventricular and supraoptic nuclei of the hypothalamus. The cell bodies are actually in the hypothalamus but they have axons that traverse the infundibulum and terminal axons in the posterior pituitary gland. This means that this part of the gland does not produce hormones; instead, it stores and secretes those made by the hypothalamus. Oxytocin is the hormone that stimulates uterine contractions by acting on the uterus. There is an increase in hormone receptors in the uterus at the end of pregnancy so it is more sensitive to the action of this hormone. The cervical dilation that happens during labor triggers even more oxytocin to be released. This will increase the force and frequency of contractions until birth. Oxytocin is also necessary for the let-down reflex in breastfeeding. It is felt to be involved in feelings of love and closeness, as well as the sexual response cycle. Antidiuretic hormone affects the blood osmolarity or concentration of solutes in the bloodstream. Blood osmolarity is measured by osmoreceptors within the hypothalamus; a high osmolarity will signal ADH release from the posterior pituitary gland. The target cells are the tubular cells of the kidneys with allow for increased water absorption. This will decrease the osmolarity of the blood, achieving homeostasis. High concentrations of vasopressin will raise the blood pressure by increasing peripheral resistance.

ANTERIOR PITUITARY GLAND The anterior pituitary gland originates from embryonic digestive tract tissues that migrate to the brain. There are three separate regions to this part of the gland: the pars distalis, the pars intermedia, and the pars tuberalis (which wraps around the infundibulum). The production and release of hormones from the anterior pituitary gland are regulated by the hypothalamus. There is a hypophyseal portal system—a collection of capillaries—that sends the hormones through the blood from the hypothalamus to the pituitary gland.

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Growth hormone or “somatotropin” regulates the growth of the human body, cellular replication, and protein synthesis. It promotes tissue building directly and indirectly. There are two hormones that regulate GH synthesis: GHRH (growth hormone releasing hormone) and GHIH (growth hormone inhibiting hormone or somatostatin)—both of which are released by the hypothalamus. Growth hormone does several things: it accelerates protein synthesis in the bones and skeletal muscles; it activates insulin-like growth factor-1; it stimulates lipolysis (adipose tissue breakdown), which causes fatty acids to be used in metabolism; it causes the breakdown of glycogen in the liver to make glucose; it enhances cellular proliferation and inhibits programmed cell death. The anterior pituitary gland also secretes TSH or thyroid stimulating hormone. It does so because of the release of thyrotropin releasing hormone (TRH) from the hypothalamus. The negative feedback loop goes like this: first TRH is released to cause TSH secretion. Then, the TSH causes thyroxine (T4) and triiodothyronine (T3) to be released by the thyroid gland. The increased levels of these two hormones feedback to decrease the TRH level in the hypothalamus. This decreases TSH production. ACTH is also called corticotropin or adrenocorticotropic hormone. Its role is to stimulate the adrenal cortex to secrete cortisol and related hormones. ACTH is similar to melanocyte stimulating hormone and endorphins. The release of ACTH is regulated by CRH (corticotropin releasing hormone) from the hypothalamus. ACTH and cortisol are crucial in the stress response. FSH and LH are the reproductive hormones secreted by the anterior pituitary gland. They have functions in both males and females. GnRH (gonadotropin releasing hormone) from the hypothalamus triggers the release of these hormones and participates in the negative feedback loop with regard to the reproductive hormones. Both FSH and LH are referred to as gonadotropins. Both of these hormones are glycoproteins. FSH causes sex cell production and maturation, while LH triggers ovulation and regulates the production of estrogen and progesterone in the ovaries. In males, LH stimulates testosterone production.

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Prolactin promotes lactation in women. It helps in the development of the mammary glands in pregnancy so they can produce milk. Its function depends heavily on the permissive effects of other female hormones as well as on oxytocin production. Dopamine (also referred to as prolactin inhibiting hormone) blocks prolactin secretion in non-pregnant women. Prolactin releasing hormone is made in the hypothalamus but it is only helpful in increasing prolactin production in pregnancy. The cells between the two lobes secrete melanocyte stimulating hormone, which has a complicated function when produced by the pituitary gland. The concentration is the same in light-skinned as in dark-skinned people. It is only locally-made MSH in the skin that increases melanin production in humans. Women in pregnancy will have increased MSH production which, along with increased estrogen levels, will cause increased skin pigmentation in certain body areas.

ADRENAL GLANDS There are two adrenal glands, located atop each kidney and made from a combination of glandular and neuroendocrine tissue. They have a high rate of blood flow and are served by three arteries each. Blood flow goes from the outer cortex of the adrenal gland to the inner adrenal medulla and finally out of the left and right suprarenal veins. There are several layers to the adrenal glands. The outer cortex has three layers: the zona glomerulosa, the zona fasciculata, and the zona reticularis. Each secretes separate hormones. The adrenal cortex participates in the hypothalamic-pituitary-adrenal (HPA) axis, which is the feedback loop involved with cortisol production. The adrenal medulla is neuroendocrine tissue made from postganglionic sympathetic nervous system neurons. As mentioned in the previous chapter, the sympathetic nervous system directly connects the preganglionic fibers to the adrenal medulla, which secretes epinephrine and norepinephrine in response to stimulation. The adrenal medulla’s function is to respond to stress.

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Short-term stress involves the fight-or-flight response via the sympathetic-adrenal medulla pathway. It prepares the body for physical exertion. Once the stressor is gone, the body returns to normal. If the stress is not relieved, there is adaptation to stress, called the stage of resistance. Long-term stress leads to a state of exhaustion, with immune suppression, fatigue, and other illnesses. In the adrenal cortex, there are three zones. These are depicted in figure 78:

The most superficial layer of the adrenal cortex is the zona glomerulosa, which is responsible for making mineralocorticoids, which affect the balance of sodium and potassium in the body. The most common mineralocorticoid made is aldosterone, which is released when the potassium is high, the sodium is low, the blood pressure is low, or there is low blood volume. It increases potassium excretion in the kidneys and reduces sodium excretion so the blood volume, sodium level, and blood pressure increase. Its secretion is turned on by ACTH production.

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The next deepest layer is the zona fasciculata, which helps secrete glucocorticoids, the most important of which is cortisol. In response to long-term stressors, the hypothalamus will secrete CRH, in turn triggering ACTH, which stimulates glucocorticoid release. The net effect is to stimulate breakdown of nutrients to be used as a fuel supply. It causes the breakdown of glycogen into glucose, the breakdown of triglycerides into fatty acids and glycerol, and the breakdown of protein into amino acids. The zona reticularis is the deepest layer of the adrenal cortex and produces the androgen hormones. These hormones supplement the androgens made by the gonads, which produce much more of these hormones when compared to the adrenal glands. It is the major source of estrogen produced by women in the postmenopausal years. The adrenal medulla produces catecholamines. It is part of the sympathetic nervous system. The cells of the medulla are called chromaffin cells that make epinephrine and norepinephrine. Epinephrine is more powerful than norepinephrine and is made in greater amounts by these cells. The end result of these hormones is dilation of the pupils, dilation of the airways, increased blood glucose levels, increased heart rate, and increased blood pressure. The circulation increases to the brain, lungs, heart, and skeletal muscle; it decreases in the GI tract, skin, and kidneys. The immune system is downregulated.

THYROID GLAND The thyroid gland is located in the anterior neck in front of the trachea and beneath the larynx. It consists of two lobes, separated by an isthmus (bridge). The tissue is made of thyroid follicles that have a sticky fluid called colloid within each one. The colloid is where thyroid hormone is made. The production of thyroid hormone is entirely dependent on iodine in the system. The follicle cells secrete thyroglobulin, which binds with iodine, which is trapped in the colloid by the follicle cells. T4 or thyroxine has four iodine molecules attached, while T3 or triiodothyronine has three iodine molecules attached. T4 and T3 remain in the colloid center of the thyroid follicles until TSH from the pituitary gland stimulates the reuptake of colloid back into the follicle cells. Enzymes break apart the

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thyroglobulin molecule, releasing free T4 and T3, which exit the cell membrane to enter the bloodstream. Less than 1 percent is unbound; the rest is bound by thyroxine binding globulins or other plasma proteins. These are gradually leached off the proteins and into target cells as free hormones. T3 and T4 are metabolic hormones because their hormones influence the basal metabolic rate of the body, which is the amount of energy the body uses at rest. When T3 and T4 bind to intracellular receptors on the mitochondria, they cause the breakdown of nutrients and the use of oxygen to make ATP. This is an inefficient process, with the formation of heat as a byproduct of these types of reactions. A high production of heat increases body temperature. Thyroid hormones are also important for fetal and childhood development; they continue to support normal neurological function in adults. Reductions in thyroid hormone can affect fertility, libido, and reproductive function. The presence of thyroid hormone is necessary for catecholamine sensitivity by upregulating the numbers of catecholamine receptors in the blood vessels. High hormone levels will increase body heat, increase the blood pressure, strengthen the heartbeat, and increase the heart rate. This is why thyroid disorders have several associated symptoms throughout the body. A lesser known hormone produced by the thyroid gland is called calcitonin. This is made by C cells, also called parafollicular cells between the follicles. The production of calcitonin is triggered by high blood calcium levels; it acts to decrease the calcium level in the bloodstream. It does this by inhibiting osteoclast activity, increasing osteoblast activity, increasing calcium loss in the urine, and decreasing the calcium absorption in the intestinal tract. Interestingly, it does not play a huge role in calcium homeostasis, as other molecules have a greater activity in doing this.

PARATHYROID GLANDS The parathyroid glands are four tiny glands found imbedded in the back surface of the thyroid gland, separated from the gland by a connective tissue capsule. There is more than one type of cell in the parathyroid gland; however, the chief cells are the ones that make the parathyroid

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hormone or PTH. It is the major hormone involved in the homeostasis of calcium levels in the bloodstream. PTH increases the calcium level in the bloodstream by stimulating osteoclasts to break down bone, inhibiting osteoblast activity, increasing calcium reabsorption in the kidneys, and increasing calcitriol production (the active form of vitamin D3). The calcitriol stimulates the absorption of calcium in the diet. There is a negative feedback loop, in which rising calcium levels block further release of PTH by the parathyroid glands.

PINEAL GLAND The pineal gland is below and behind the thalamus. It is made of cells called pinealocytes, which produce the amine hormone called melatonin. The secretion of melatonin varies according to the amount of light in the environment. There is a nerve stimulus sent by light reaching the retinas to a part of the hypothalamus called the suprachiasmatic nucleus. The signal goes from there to the pineal gland where melatonin production is inhibited. As nighttime approaches, the melatonin production increases, creating a state of drowsiness. It is likely that melatonin influences the body’s circadian rhythm, which also affects body temperature and appetite. Children have higher melatonin levels than adults, which may inhibit the onset of puberty. Jet lag is caused by crossing many time zones. It takes several days for individuals to regulate the natural levels of melatonin in order to adjust to the day-night patterns in a new environment.

ENDOCRINE PANCREAS The pancreas is a long, slim organ located mainly behind and slightly below the stomach. It has endocrine and exocrine functions. The endocrine function is involved with the pancreatic islet cells (previously known as the islets of Langerhans). Within these islets, four hormones are secreted: somatostatin, insulin, glucagon, and pancreatic polypeptide (PP). There are four types of cells in the pancreatic islets, including these: •

Alpha cells—these make glucagon, which raises the blood sugar levels in response to low blood sugars. 195

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Beta cells—these make insulin, which lower the blood sugar in response to high blood sugar levels.

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Delta cells—these account for just 4 percent of the islet cells and secrete somatostatin, which is also secreted by the hypothalamus, stomach, and intestines. It inhibits both glucagon and insulin release.

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PP cells—these account for about 1 percent of the islet cells. It secretes pancreatic polypeptide, which plays a role in appetite, decreasing after a meal as well as after fasting.

Insulin and glucagon regulate the blood sugar levels in the body. Insulin comes from the diet and, if not immediately used, it is made into glycogen by the liver or triglycerides in fatty tissue. Hormones regulate the storage and usage of glucose in the body. There are receptors in the pancreas that sense blood sugar levels and allow for the secretion of glucagon or insulin in order to maintain normal blood sugar levels. Glucagon stimulates the conversion of glycogen back into glucose, a process called glycogenolysis. It also stimulates the liver to take amino acids and make glucose out of them. Triglycerides are also broken down by the body in a process called lipolysis, which makes glycerol that is converted into glucose in the liver. The effect is to increase the blood sugar. Insulin acts to decrease blood sugar by facilitating its uptake into cells to be used for metabolism. Cells that don’t require insulin for sugar uptake are the kidneys, brain, red blood cells, liver, and small intestinal lining. Skeletal muscle and adipose tissue are the main target cells for insulin. Food in the intestinal tract will stimulate hormones that turn on insulin production. Once the nutrients are taken up, the elevation in blood sugar further increases the insulin level. Insulin also decreases blood sugar levels by stimulating the metabolism of glucose for ATP generation. It also stimulates the production of glycogen, inhibiting both glycogenolysis and gluconeogenesis. Lastly, it also promotes triglyceride and protein synthesis. The feedback of insulin production is the glucose level itself. Once it is lowered, insulin production is toned down and glucagon synthesis begins. 196

SECONDARY ENDOCRINE ORGANS There are several body organs and tissues that aren’t necessarily part of the endocrine system but have endocrine function. Let’s review these functions as they relate to the endocrine system: •

Heart—the cells of the atria of the heart produce an enzyme called atrial natriuretic peptide (ANP) in response to stretch of the heart muscle wall. It signals a loss of sodium and water in the kidneys, resulting lowered blood volume, lowered blood pressure, and decreased sodium levels.

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GI tract—there are endocrine cells in the GI tract (the stomach and small intestine), such as gastrin, which is released by stomach distension. Gastrin causes a stimulation of hydrochloric acid secretion in the stomach. Secretin is another hormone that stimulates bicarbonate release in the duodenum and decreases hydrochloric acid secretion in the stomach. Cholecystokinin is released by the small intestine and causes bile and pancreatic enzymes to be released.

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Kidneys—the kidneys participate in the renin-angiotensin-aldosterone system that regulates blood pressure and blood volume. It also produces calcitriol from vitamin D3, which stimulates calcium production. Finally, it makes erythropoietin, which stimulates red blood cell production in the bone marrow.

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Skeleton—there are two relatively unknown hormones produced by the skeleton. The first is fibroblast growth factor-23, which blocks the formation of calcitriol from vitamin D3 and increases phosphorus excretion. The second is osteocalcin, which is made by osteoblasts and causes the pancreas to secrete insulin.

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Adipose tissue—there are several hormones made by fatty tissue. Leptin is made by fat cells in response to food consumption and acts by binding to brain neurons involved in the expenditure of energy. Leptin is what creates satiety after a meal. Adiponectin is also secreted by adipose cells; it reduces cellular insulin resistance and protects blood vessels from inflammation and atherosclerosis.

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Skin—this produces cholecalciferol in the presence of ultraviolet light. In the liver, this is converted to active vitamin D3 or calcitriol. Vitamin D is important in intestinal calcium absorption and immune functioning.

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Thymus—this is an immune system gland important in childhood but not as much in adulthood. It makes thymosin, which is actually a group of immune cells that help to develop and differentiate T lymphocytes, contributing to the immune response in ways that are not fully understood.

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Liver—there are at least four important hormones produced by the liver, although some are actually hormone precursors. There is somatomedin (insulin-like growth factor), thrombopoietin, angiotensinogen, and hepcidin. Somatomedin will stimulate growth in the body; angiotensinogen makes angiotensin (important in raising blood pressure); thrombopoietin stimulates platelet production; and hepcidin blocks the release of iron from the cells of the body, regulating iron homeostasis.

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KEY TAKEAWAYS •

The command center of the endocrine system is the pituitary-hypothalamus complex.

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There are two major divisions to the pituitary gland; the anterior part mainly makes hormones that turn on other endocrine tissues.

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The adrenal gland has endocrine and neural origins with the cortex and medulla, respectively.

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The thyroid gland is mainly involved in metabolism.

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The pancreas has major endocrine functions, making four endocrine hormones.

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Many areas of the body have secondary endocrine functions, producing lesser-known hormones.

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QUIZ 1. Which hormone is not made by the thyroid gland? a. Thyroxine b. Calcitonin c. Triiodothyronine d. Parathyroid hormone Answer: d. Parathyroid hormone is created by the parathyroid glands, which are next to the thyroid gland but not part of the thyroid gland. The others are made by the thyroid gland itself. 2.

Which hormone is made by the posterior pituitary gland? a. Thyroid stimulating hormone b. Follicle stimulating hormone c. Antidiuretic hormone d. Growth hormone Answer: c. Antidiuretic hormone or ADH is made by the posterior pituitary gland and helps to regulate water balance in the body. The other hormones are made by the anterior pituitary gland.

Which hormone is not considered a steroid hormone? a. Testosterone b. Estrogen c. Cortisol d. Follicle stimulating hormone Answer: d. Each of these is a steroid hormone, except for follicle stimulating hormone, which is a glycoprotein molecule.

Which of the following is an amine hormone that is synthesized from tryptophan? a. Epinephrine 200

b. Dopamine c. Melatonin d. Thyroxine Answer: c. Each of these are amine hormones, modified amino acids, but only melatonin is synthesized from the amino acid called tryptophan. The others are based on tyrosine. 5.

Which two hormones have opposing actions with one another? a. FSH and LH b. Estrogen and progesterone c. TSH and thyroxin d. Glucagon and insulin Answer: d. Insulin and glucagon are both secreted by the pancreas and have completely opposing effects on the body. Glucagon raises blood sugar, while insulin lowers blood sugar.

Which hormone is secreted by the intermediate zone of the pituitary gland? a. Oxytocin b. Melanocyte stimulating hormone c. Antidiuretic hormone d. Corticotropin releasing hormone Answer: b. Melanocyte stimulating hormone is secreted by the intermediate zone of the pituitary gland. It stimulates melanocytes to make melanin and is structurally related to ACTH. Oxytocin and antidiuretic hormone are secreted by the posterior pituitary gland, while corticotropin releasing hormone is secreted by the hypothalamus.

Which layer represents the most superficial layer of the adrenal gland? a. Zona glomerulosa b. Zona fasciculata

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c. Zona reticularis d. Medulla Answer: a. The zona glomerulosa lies just beneath the adrenal capsule and is the most superficial of the adrenal layers. 8.

What hormone classification is made in the zona fasciculata of the adrenal glands? a. a. Catecholamines b. b. Mineralocorticoids c. c. Sex hormones d. d. Glucocorticoids Answer: d. The glucocorticoids are the classification of hormones produced by the zona fasciculata in the adrenal glands.

Which mineral is important in the production of thyroid hormones? a. Manganese b. Iron c. Iodine d. Magnesium Answer: c. Iodine is an integral part of thyroid hormone production. It is incorporated as part of each of the two thyroid hormone molecules.

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What will least likely happen with an increased level of thyroid hormone in the body? a. Increased blood pressure b. Heat intolerance c. Increased heart rate d. Decreased metabolic rate Answer: d. Increased levels of thyroid hormone will increase the metabolic rate, not decrease the metabolic rate.

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CHAPTER NINE: HEART ANATOMY AND PHYSIOLOGY The heart plays a central role in the cardiovascular system, as the major pump that forces blood throughout the body. The cells of the heart (cardiac muscle cells) have a unique electrical activity and synchronize the activity of the chambers of the heart. The coronary arteries are the major arteries supplying the heart; they are important because damage to any of these arteries potentially can cause a heart attack.

BASIC HEART ANATOMY The heart is located within the thoracic cavity, roughly in the middle of the cavity. In anterior portion of the heart is the mediastinum. The heart is separated by the mediastinum by the pericardium or “pericardial sac,” sitting in the pericardial cavity, which consists mainly of the heart. The posterior portion of the heart is near the thoracic vertebrae. Figure 79 illustrates the anatomy of the heart in the chest:

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The base of the heart is actually the top surface of the heart, where the major blood vessels enter and exit the heart. This means that the inferior tip of the heart is the apex, lying just to the left of the sternum between the fourth and fifth rib junction to the sternum. The heart is slightly tilted from front to back, with the right side being more anterior than the left. The apex of the heart is tucked into a depression in the left lung, called the cardiac notch. The heart is shaped like a pinecone, being broader at the base and tapering at the apex. It is about the size of the human fist. It weighs between 250 and 350 grams, being larger in trained athletes. When the heart is exercised aerobically, myofibrils are added to existing muscle cell fibers so that the heart is larger. Hypertrophic cardiomyopathy is a non-exercise-related condition in which there is focal enlargement of parts of the heart muscle, leading to sudden death in young people. There are four chambers in the heart: two atria and two ventricles. The upper chambers are the atria, while the lower chambers are the ventricles. The atria are receiving chambers that push blood into ventricles, which pump blood out of the heart. There are two distinct circuits in the circulatory system: the pulmonary and systemic circulation. The pulmonary circuit transports blood to and from the lungs, while the systemic circulation transports oxygenated blood to the rest of the body. Figure 80 shows the basic anatomy of the heart:

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The pulmonary trunk is where the deoxygenated blood first exits the right ventricle. It splits into the left and right pulmonary arteries. The arteries branch out many times before reaching the tiny pulmonary arteries, where there is exchange of the oxygen for carbon dioxide in the alveoli of the lungs. This leads to oxygenated blood pumping back through the veins to reach the pulmonary veins, which enter the left atrium. The left atrium pumps blood into the left ventricle, which pumps oxygenated blood into the aorta and systemic circulation. These lead to systemic capillaries, where oxygen exchanges with carbon dioxide, leading to deoxygenated blood passing through venules and veins. This finally leads to the superior and inferior vena cava, which enter the right atrium to start the entire process over again. The right atrium sends blood to the right ventricle and back to the lungs. The tough membrane that surrounds the heart is called the pericardial sac, pericardium or pericardial membrane. It surrounds the roots of the major blood vessels exiting and entering the heart. There are two layers to this membrane. There is the fibrous and serous pericardium. The serous pericardium consists of two layers: the parietal pericardium (fused to the fibrous pericardium) and the epicardium, which is fused to the heart and is part of the heart wall. The pericardial cavity has a small amount of lubricating serous fluid that helps lubricate the heart as it beats in the pericardial space. There is a layer of simple squamous epithelium in the visceral serous membranes that secretes the fluid. There is a superficial leaf-shaped extension of each atrium at the base of the heart called an auricle. It will fill with blood during systole (contraction of the heart) and empty of blood during diastole (relaxation of the heart). There are grooves filled with fat that lie along the upper surface of the heart, called sulci. This is the location of the major coronary arteries that surround the heart. The deep coronary sulcus is located between each atrium and each ventricle. There are less-deep sulci between the left and right ventricles. The deep coronary anterior interventricular sulcus is along the front surface of the heart; the posterior interventricular sulcus is along the back surface of the heart; the coronary sulcus is between the atria and ventricles.

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There are three layers in the heart itself. These include the epicardium (located on the outside), the myocardium (the thick muscle layer), and the endocardium (the thin inner layer). The myocardium consists mainly of cardiac muscle fibers with a framework of collagenous fibers, blood vessels, and nerve fibers. The muscle fibers curve around the atria and ventricles in a figure of 8 pattern. It allows the muscle to contract more efficiently than it would if the muscle fibers were straight. The muscle of the left ventricle is thicker because, while it pumps the same amount of blood as the right ventricle, it needs to overcome the high resistance necessary to pump blood through the systemic circulation. The inner lining of the heart is the endocardium, which Is connected to the myocardium. It is made from simple squamous epithelial cells that compose the endothelium. The endothelium is contiguous with the endothelial lining of the blood vessels of the body. It secretes endothelin molecules that affect the ionic concentrations in the tissues, changing the state of contractility of the heart. There are several septa (plural of septum) or walls in the heart that separate the different chambers. These have myocardium and endocardium but no epicardium. There is an interatrial septum that separates the atria. There is an oval depression in the septum called the fossa ovalis (the remnant of the foramen ovale in the fetus). The foramen ovale allowed blood to flow between the chambers in the fetus; a flap of tissue called the septum primum closes the foramen ovale a few seconds after birth to create a separation of the two chambers. Between the two ventricles is the interventricular septum. It is intact from fetal times and is thicker than the interatrial septum. Between the atria and ventricles is the atrioventricular septum. There are four openings that allow blood to move between the atria and ventricles and from the ventricles to the pulmonary trunk or aorta. Within each of the openings is a valve that opens and closes in order to keep the blood flowing in one direction. The valves between the atria and ventricles are called atrioventricular valves, while the valves that lead out of the heart are called semilunar valves. There is a fibrous skeleton called the cardiac skeleton that reinforces the AV septum, which is made from dense connective tissue.

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RIGHT ATRIUM The right atrium is the receiving chamber for blood that comes back from the systemic circulation via the inferior and superior vena cava, as well as the coronary vein, which receives blood from the myocardium of the heart. The superior vena cava drains blood from the arms, head, neck, and upper chest. The inferior vena cava drains blood from the abdomen, pelvis, and legs. The coronary sinus drains blood from the heart and is located just above and slightly medial to the inferior vena cava opening. In the atrium itself, there are pectinate muscles in the wall of the muscle. The blood returns from the heart on a regular basis (during all stages of heart muscle contraction and relaxation). The opening outflow tract of the right atrium is the tricuspid valve. There is no valve that blocks the vena cava from entering the right atrium.

RIGHT VENTRICLE The right ventricle receives blood via the tricuspid valve from the right atrium. Each flap of the valve is attached to connective tissue strands called chordae tendineae. There are several of these strands associated with each flap of the tricuspid valve. These cords are 80 percent collagen and 20 percent elastin plus endothelium. They connect the flaps to a papillary muscle in the right ventricle. There are three papillary muscles connected to one of three valve leaflets in the tricuspid valve, called the anterior, posterior, and septal muscles. The papillary muscles contract during the contraction phase (systole) of the heart so that there is no backflow of blood into the right atrium. If these muscles rupture, there can be backflow of the blood back into the right atrium. The walls of the right ventricle are lined with trabeculae carneae, which are ridges of heart muscle within the ventricle, along with a moderator band, which reinforces the relatively thinner walls of the right ventricle. The moderator band arises from the lower aspect of the interventricular septum to connect with the inferior papillary muscle. When the right ventricle contracts, it sends blood through the semilunar pulmonic valve, which closes during diastole (relaxation) in order to prevent back flow of the blood from the pulmonary trunk into the right ventricle.

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LEFT ATRIUM The left atrium receives oxygenated blood from the pulmonary circulation. There are pectinate muscles only in the auricle of the left atrium. Blood flows continuously into the left atrium with no valve required. The atrium will contract toward the end of diastole, accounting for about 20 percent of the total amount of ventricular filling. The flow between the left atrium and left ventricle is guarded by the mitral valve.

LEFT VENTRICLE Although both sides of the heart pump the same amount of blood, the left ventricular walls are the thickest of all the walls of the heart. The left ventricle has trabeculae carneae but it doesn’t have a muscular moderator band. There are papillary muscles attaching the mitral valve to the left ventricular wall and there are chordae tendineae that attach the valve to the papillary muscles. There are just two papillary muscles, however; these are the anterior and posterior papillary muscles. When the ventricle contracts, the aortic valve (a semilunar valve) opens to let blood flow into the aorta. Figure 81 shows what the valves of the heart look like:

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The valves assure that there is unidirectional blood flow through the heart. Between the right atrium and the right ventricle is the tricuspid valve, with three leaflets, made from connective tissue and endocardium. It has flaps connected by chordae tendineae and papillary muscles. The pulmonic or “pulmonary” valve has three leaflets reinforced with connective tissue. There are no muscles associated with this valve. The mitral valve is a bicuspid valve with two leaflets and two papillary muscles. The aortic valve has three flaps and no muscles (similar to the pulmonic valve).

ELECTRICAL ACTIVITY OF THE HEART Recall that cardiac muscle is different from skeletal muscle in that it has the ability to initiate an electrical potential at a fixed rate that spreads from cell to cell during cardiac muscle contraction. This is known as autorhythmicity. This is something that isn’t done in smooth or skeletal muscle. The heart rate is modulated by the nervous and endocrine system. There are two types of cardiac muscle cells: a total of 99 percent of them are called “myocardial contractile cells” that will contract and conduct impulses throughout the heart; 1 percent are called “myocardial conducting cells” that form the conduction system of the heart. These tend to be smaller than the contractile cells and do not contract greatly. They act as cells which propagate the action potential like neuron cells throughout the heart. Cardiac muscle cells are shorter and smaller than regular muscle cells. There are striations, which are alternating patterns of darker A bands and lighter I bands, and contractile elements are identical to skeletal muscle. T tubules or “transverse tubules” penetrate from the sarcolemma (plasma membrane) to the interior of the cell (like in other muscle cells) and are found at the junction of the I and A bands, but only at the Z discs. Remember, the Z discs or Z bands are where the sarcomeres end and another one starts. The calcium comes from both the sarcoplasmic reticulum in a small part in cardiac cells; most come from outside the cells. This means the contraction is slower than with skeletal muscle. There are a lot of branches to cardiac muscle. The junction between two nearby cells is called an intercalated disc, which supports the synchronized contraction of the cardiac muscle. These

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discs are where the cells connect to each other and are essentially desmosomes, tight junctions, and gap junctions that allow the passage of ions between the cells, helping to bind the cells together. There is also intercellular connective tissue, which binds the cells together during contraction. Cardiac muscle undergoes aerobic respiration just like other muscle cells. Lipids and carbohydrates are metabolized in the mitochondria to make energy. Cardiac muscle cells have long refractory periods with brief relaxation periods. The relaxation period is necessary to allow the heart to fill with blood for the next cardiac cycle. The refractory period is long in order to prevent tetany of the heart muscle, which isn’t compatible with life. Damaged cardiac muscle cells cannot easily repair or replace themselves if the cell is damage. There are a few cardiac muscle stem cells that can potentially replace dead cells but those that replace dead cells aren’t as functional as the original cells. Dead cells are often replaced by inactive scar tissue.

CONDUCTION SYSTEM OF THE HEART If embryonic heart cells are grown in vitro (in a Petri dish), they can generate their own electrical impulse and contract. When they are connected, they contract together from the faster cell through to the slower cell. The heart can generate its own electrical impulse and the fastest cells lead the way for slower cells. The major components of the cardiac conduction system are the SA node (or sinoatrial node), AV node or atrioventricular node, the bundle branches, and the Purkinje cells. The SA node is where the cardiac conduction cycle begins. It is located in the upper back wall of the right atrium near where the superior vena cava enters the heart. The SA node has the fastest rate of depolarization and is considered the pacemaker of the heart. Impulse spreads from the SA node via internodal pathways through the atria to the AV node. There are three bands of internodal pathways (anterior, middle, and posterior) that lead onto the next node in the electrical pathway. It takes 50 milliseconds to travel between the nodes.

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There is a specialized pathway called the Bachmann’s bundle or the interatrial band connects the left and right atrium. The connective tissue of the cardiac skeleton prevents the impulse from getting to the ventricles by any other pathway but through the AV node. Figure 82 describes the conduction system of the heart:

The AV or atrioventricular node receives impulses from the AV node. It is located near the part of the right atrium near the atrioventricular septum. The AV node depolarizes and sends impulses down to the apex and back up the sides of the ventricles in what’s called the bundle of His. It takes about 100 milliseconds for the impulse to pass through the node. This is a crucial pause that is critical to heart function. It allows the atrial cardiac cells to complete their contraction so blood pumps into the ventricles. The bundle of His divides at the apex into the left and right bundle branches. The left bundle branch supplies the left ventricle and the right bundle branch supplies the right ventricle. The left bundle branch is bigger than the right bundle branch because of the difference in size of

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these ventricles. Each papillary muscle receives the signal at the same time so they contract simultaneously before the ventricles. The passage of the electrical impulse through the bundle of His takes 25 milliseconds. The Purkinje fibers are conductive fibers that spread the impulse throughout the ventricles. They extend throughout the myocardium from the apex toward the base of the heart. They reach the entire ventricle in about 75 milliseconds. The pathway allows the contraction of the heart to go from the apex to the base of the heart. This allows the blood to be squeezed out of the heart in a total of about 225 milliseconds. The action potentials in the cardiac conductive cells is different than the cardiac contractive cells. Sodium, potassium, and calcium are all important in both cell’s action potential activity. There is not a stable resting potential in cardiac muscle cells. Sodium ions leak into the cell continuously, allowing for spontaneous depolarization of the cell. The sodium ions cause the membrane potential to increase from -60 mV to -40 mV. Then the calcium enters the cell, causing further depolarization to +15 mV. Finally, the potassium channels open, allowing the membrane potential to go back to -60 mV before the cycle begins again. The electrical pattern of contractile cells in the heart is different from the conductive cells. There is a more rapid depolarization, followed by a plateau phase and repolarization. This allows the heart muscle to pump blood out of the heart before they can fire a second type. They usually wait for an impulse to come to them although they can pump and generate an action potential on their own if necessary. Contractile cells have a much more stable resting phase when compared to the conductive cells. The resting potential is -80 mV for the atria and -90 mV for the ventricles. The rest of the action potentials are the same for the atria and ventricles. When stimulated, the influx of ions causes the potential to go up to +30 mV, with a rapid depolarization again. This is followed by a plateau phase, where the membrane potential drops slowly. The absolute refractory period is 200 milliseconds, while the relative refractory period is about 50 milliseconds. This long period is necessary for the heart to pump blood out of the ventricles. It prevents premature contractions, which would be fatal.

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THE ELECTROCARDIOGRAM The electrocardiogram or ECG measures the electrical signal of the heart. It is a great diagnostic tool in cardiology. The standard ECG used 12 leads placed on all four extremities and on several precordial areas. The more leads, the better the diagnostic effect of the test. There are ten electrodes total to make a 12-lead ECG. Figure 83 shows a single cardiac cycle represented on an ECG lead:

As you can see, there are several major points on the ECG cycle: The P wave, the QRS complex, and the T wave. The P wave is the depolarization of the atria; the QRS complex is the depolarization of the ventricles. The ventricles start to contract at the peak of the R wave. The T wave represents the repolarization of the ventricles. The repolarization of the atria is hidden in the QRS complex. Doctors measure the PR interval and the length of the QRS complex to see if the heart muscle is healthy. If there is elevation of the QT interval, this could mean a myocardial infarction; if there is depression of the QT interval, it could mean stress or hypoxia in the heart.

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CARDIAC CYCLE The cardiac cycle is the time that begins with atrial contraction and ends with ventricular relaxation. The period of contraction of the heart is called systole, while the period of chamber filling is called diastole. Both atria and ventricles go through systole and diastole at the same time. Blood flows from an area of high pressure to an area of low pressure. The pumping of the heart leads to changes in pressure and blood flow through the heart. At the beginning of the cardiac cycle, the atria and ventricles are relaxed in diastole. Blood continually flows into the right and left atrium. There is opening of the mitral and tricuspid valves so that about 80 percent of ventricular filling happens. The pulmonic and aortic valves are closed during this phase. The atria contract during the P wave of the ECG and provide an atrial kick that pushes another 20 percent of the blood into the ventricles. This lasts 100 milliseconds and ends just before ventricular systole. Ventricular contraction and systole happen just after depolarization of the ventricles at about the time of the R peak. At the end of atrial systole, the ventricles contain about 130 milliliters of blood, called the end diastolic volume or “preload.” The ventricles begin to contract but do not initiate release of the blood in them yet—a period of time called isovolumic contraction. This is followed by the ventricular ejection phase, with release of blood out of the heart. The stroke volume is the amount of blood ejected from the heart, which is 70 milliliters. This leaves about 60 milliliters left in the heart as the end-diastolic volume. The relaxation phase or diastole of the heart occurs during the T wave and lasts about 430 milliseconds. The pressure falls to low levels and some blood backs up toward the ventricles from the pulmonary and systemic circulations. It is then that the semilunar valves close and there is a period of isovolumic ventricular relaxation phase (in which the volume of blood doesn’t change). Then there is further relaxation of the muscle with blood filling into the ventricles from the atria. This leads to both chambers in diastole again. The heart sounds are important to the cardiac evaluation. There is an S1 sound, in which the AV valves close and the ventricles are in systole. This is follows by the S2 sound, in which the

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semilunar valves close, starting the isovolumic phase of diastole. A third sound called S3 is rarely heard. It is the sound of the blood in the atria, the sound of blood sloshing in the ventricles, or the tensing of the chordae tendineae. It may be normal in young people but, in older people, it represents the possibility of congestive heart failure. An S4 sound stems from contraction of the atria into a stiff ventricle and is abnormal. What is occasionally referred to as an S7 is the combination of an S3 and S4 in the same person. A heart murmur is the sound of turbulent blood flow. It can be graded on a scale of 1 through 6, with 6 being the loudest murmur. Certain maneuvers like the Valsalva (bearing down) maneuver and deep breathing can change the quality of the murmur and can help identify the source of the murmur. Murmurs can be diastolic or systolic in nature and can represent narrowed flow through a valve or the backflow through a leaky valve.

CARDIAC PHYSIOLOGY The heart beats at a regular pace because of its autorhythmicity. There are some important aspects of cardiac function that you should know about. For example, the cardiac output or CO of the heart is the stroke volume times the heart rate in contractions per minute or beats per minute (bpm). The stroke volume is the end diastolic volume minus the end systolic volume and is about 70 milliliters. The range in cardiac output is about 4-8 liters per minute or about 5.25 liters per minute on average. There are things that affect this number. Factors affecting heart rate include hormones, autonomic input, fitness levels, and age. Factors affecting the stroke volume include heart size, fitness levels, preload, afterload, gender, duration of contraction, and contractility of the heart muscle. The ejection fraction is another important measurement in the heart function. This number, the EF, is the SV divided by the end diastolic volume. The average EF is about 58 percent, with a range of 55-70 percent. The cardiac reserve is the difference between the maximum cardiac output and the resting cardiac output and is a measure of the reserve or potential of the heart to pump blood during exercise.

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HEART RATE The heart rate is between 60 and 100 in adults, with a maximum HR of about 200-220 bpm. The maximum HR will decrease with age so it’s about 220 minus a person’s age. As the HR increases, there is less time in diastole for filling but the stroke volume will remain high for a period of time. As HR goes further up, the stroke volume will drop. The goal of aerobic exercise is to get within the target heart rate of between 120 and 160 bpm. The brain input over the heart rate comes from two paired cardiovascular centers in the medulla. The cardioaccelerator center uses sympathetic tone to increase the heart rate, while the cardioinhibitory centers use parasympathetic tone to decrease the heart rate. This uses the vagus nerve to contribute to the autonomic tone of the heart. If there was no vagal (parasympathetic) tone, the SA node would initiate a heart rate of about 100 beats per minute. There is a cardiac plexus of nerves located near the base of the heart that comes out of signals from the cardioaccelerator centers and cardioinhibitory centers of the heart. There are more sympathetic nerve fibers on the heart when compared to parasympathetic fibers. Norepinephrine is released at the neuromuscular junction of the cardiac nerves. This will increase the heart rate. Parasympathetic innervation relies on acetylcholine at the neuromuscular junction. This will decrease the heart rate. Increases in heart rate above 100 require sympathetic stimulation. There are various proprioceptors, baroreceptors, and chemoreceptors that influence the heart rate and cardiac output. These result in what are called cardiac reflexes. Increases in physical activity in the muscles, joints, and tendons results in an increased heart rate. There are baroreceptors in the vena cava, carotid bodies, and the aorta that will cause a baroreceptor reflex based on the blood pressures detected in these areas. The atrial reflex or Bainbridge reflex changes the heart rate based on the rate of blood flow in the atria. Chemoreceptors look at byproducts of physical activity (like CO2, hydrogen ions, and lactic acid) to change the heart rate. The factors that change the heart rate include the following:

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Cardioaccelerator nerves—increase heart rate by releasing norepinephrine

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Proprioceptors—increase heart rate during exercise

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Chemoreceptors—increase heart rate with low O2, high hydrogen ions, high CO2, and high lactic acid levels

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Baroreceptors—increase heart rate with a fall in blood volume and blood pressure

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Limbic system—increase heart rate with strong emotions or anticipation of exercise

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Thyroid hormones—increase heart rate with increasing T3 or T4

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Calcium—increased calcium ion will increase heart rate

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Potassium—decreased potassium will increase heart rate

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Sodium—low sodium will increase the heart rate

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Body temperature—increased body temperature will increase heart rate

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Nicotine and caffeine—will increase heart rate

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Cardioinhibitory nerves—will decrease heart rate through acetylcholine

STROKE VOLUME The same factors affecting heart rate will affect the stroke volume. The three major things affecting stroke volume are preload (or ventricular stretch in diastole), contractility of the heart muscle, and afterload (or resistance to outflow). Preload is the same thing as end diastolic volume. This depends on filling time of the heart in diastole. If the heart rate is high, the end diastolic volume or preload is lower. This can be compensated by increasing the stroke volume to a degree. The greater the stretch of ventricular muscle, the more powerful the contraction is (within limits). This will increase the stroke volume. The more forceful the contraction is, the greater is the stroke volume.

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Inotropic factors account for changes in the contractility of the heart. There are positive and negative inotropic factors. Sympathetic stimulation is positively inotropic; the reverse is true of parasympathetic stimulation. There are many drugs that can be positive or negative inotropes. Afterload is the resistance against outflow of the heart. Valve narrowing to the outflow of the heart will increase the afterload. Increased vascular resistance will increase the afterload. In the same way, decreased afterload happens with low blood pressure or decreased resistance to the outflow of the heart.

CORONARY ARTERIES The coronary arteries are vital to cardiac function. The heart is a pump that requires adequate blood flow. An interesting fact about this is that the coronary blood flow doesn’t have a lot of redundancy. There aren’t many arteries that supply the same part of the heart. This is why damage to the coronary arteries or narrowing from atherosclerosis will lead more easily to cardiac muscle damage when compared to other parts of the body. Coronary blood flow is maximal during diastole and is nearly stopped during systole. The coronary arteries come from the first portion of the aorta just after it comes out of the left ventricle. Two sinuses or dilations of the aortic wall give rise to the left and right coronary arteries. A third sinus in the aorta doesn’t give rise to any vessel. The arteries branch out and follow the sulci in the heart called epicardial coronary arteries. The left coronary artery gives rise to the circumflex artery that goes to the back of the heart, while the left anterior descending artery will go down the anterior interventricular sulcus. The right coronary artery goes along the coronary sulcus and supplys blood to the conduction system, the right atrium, and parts of both ventricles. There are marginal arteries that branch off of this and, in the back of the heart, the posterior interventricular artery or posterior descending artery supplies the back of the heart. Figure 84 shows the coronary arteries:

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The coronary veins will drain the heart. They parallel the arteries of the heart with the great cardiac vein along the front surface of the heart in the interventricular sulcus. The posterior cardiac vein parallels and drains the areas supplied by the marginal and circumflex arteries in the heart. There is a middle cardiac vein and a small cardiac vein that drain other parts of the heart. The coronary sinus is a large vein on the back of the heart that drains into the right atrium. There are also anterior cardiac veins that parallel the small cardiac arteries, draining into the anterior surface of the right ventricle, bypassing the coronary sinus.

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KEY TAKEAWAYS •

The heart is a pump made from cardiac muscle that contains four chambers: two atria and two ventricles.

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There are valves between the atria and ventricles and leading out of the ventricles that prevent backflow of blood in the heart.

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The heart cycles through systole (contractile phase) and diastole (relaxation phase).

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Cardiac muscle cells can be contractile or conductive and all have electrical automaticity.

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There is sympathetic and parasympathetic input to the heart with parasympathetic tone predominating to keep the heart rate below 100 beats per minute.

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The coronary arteries supply blood to all the heart and come from aortic sinuses just at the origin of the aorta from the heart.

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QUIZ 1. Which chamber of the heart first receives oxygenated blood from the lungs? a. Left atrium b. Right atrium c. Left ventricle d. Right ventricle Answer: a. The left atrium first receives oxygenated blood from the lungs, sending in onto the left ventricle. 2.

Which chamber of the heart sends blood to the rest of the body? a. Left atrium b. Right atrium c. Left ventricle d. Right ventricle Answer: c. The left ventricle contracts to send blood to the rest of the body (the part not involved in the pulmonary circulation).

What is the flap of tissue that closes over the foramen ovale shortly after birth? a. Fossa ovalis b. Interventricular septum c. Septum primum d. Interatrial septum Answer: c. The septum primum is a flap of tissue that separates the two atria shortly after birth by closing over the foramen ovale, a hole between the atria that exists in fetal circulation.

What is the valve called that separates the inferior and superior vena cava from the right atrium? a. Tricuspid valve 221

b. Semilunar valve c. Bicuspid valve d. There is no valve Answer: d. There is no valve that separates the inferior and superior vena cava from the right atrium. 5.

Which valves of the heart are open during systole? a. Pulmonic and aortic valves b. Aortic and mitral valves c. Tricuspid and mitral valves d. Tricuspid and pulmonic valves Answer: a. The pulmonic and aortic valve open during systole or contraction of the heart in order to allow blood to leave the ventricles.

What is a major difference between cardiac and skeletal muscle? a. There are no T tubules in cardiac muscle. b. There are branches in cardiac muscle. c. There are no Z lines in cardiac muscle. d. The contraction doesn’t involve calcium. Answer: b. The major difference between cardiac muscle and skeletal muscle is that cardiac muscle has branches.

Which ion is not important in the contractility of cardiac muscle cells? a. Sodium b. Potassium c. Calcium d. Magnesium Answer: d. Each of these ions is important in the contractility of cardiac muscle cells except for magnesium, which does not play a role.

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What is the resting potential of the cardiac conductive muscle cell before the muscle contracts? a. -60 mV b. -40 mV c. +5 mV d. +40 mV Answer: a. The initial resting potential of the cardiac conductive muscle cell before the muscle contract is -60 mV but it changes continually with the leakage of sodium ions into the cell.

In a cardiac cycle, what happens first? a. Both the ventricles and atria are in diastole b. The atria are in systole and the ventricles are in diastole c. Both atria and ventricles are in systole d. The ventricles are in systole and the atria are in diastole Answer: a. At the beginning of the cardiac cycle, the atria and ventricles are in diastole at the same time.

10.

What is the 70 milliliters of blood that leaves the heart with each contraction called? a. Preload b. Ejection fraction c. End diastolic volume d. Stroke volume Answer: d. The stroke volume is about 70 milliliters, which is the amount of blood that exits the heart with each contraction.

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CHAPTER TEN: BLOOD AND BLOOD VESSEL ANATOMY AND PHYSIOLOGY There are arteries, veins, and capillaries that allow for blood flow and gas exchange in the tissues after oxygenated blood is pumped out of the heart and before deoxygenated blood reenters it. The components of blood and blood typing are also an important aspect of the cardiovascular system and are topics in this chapter.

BLOOD COMPONENTS Blood is a type of connective tissue made from several components, namely red blood cells (RBCs), white blood cells (WBCs), and platelets, which are cell fragments without nuclei. The extracellular matrix is called plasma, which is mainly water. It suspends the cellular forms. Blood has many functions, including the delivery of oxygen and nutrients to other tissues, the removal of wastes from tissues, defense against pathogens, heat distribution, and the maintenance of homeostasis. The transportation function of blood is the ability of this tissue to transport nutrients from the digestive tract, the transportation of oxygen to tissues, the movement of hormones, the removal of carbon dioxide, and the removal of other waste products to the liver or kidneys, in the form of bile or urine. WBCs participate in the defense of the body against pathogens that have entered the tissues or bloodstream. There can also be cells that have mutated DNA that may become cancerous or virally-infected cells that need to be killed off. Blood platelets act in the defense of the body by making clots whenever tissues and blood vessels are ruptured. Blood also plays a role in body temperature regulation. A rising body temperature will cause blood vessels to dilate in the skin and periphery in order to lower the temperature of the body. This process is reversed when the environment is cold. Finally, blood will tend to maintain the chemical balance in the body by having buffers that regulate the pH of the tissues of the body.

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The blood is mostly water and red blood cells. The packed cell volume or volume of RBCs is about 45 percent. This is also referred to as the hematocrit, which is about 41 percent in females and about 47 percent in males. The percentage of plasma is about 59 percent in females and 53 percent in males. Blood is either dusky red or bright red, depending on the amount of oxygen that is in the sample. Its viscosity is about 5 times that of water, making it have some resistance to flow. The temperature of blood is about 100.4 degrees, slightly higher than a normal internal body temperature. This is because of the friction created by viscous blood in the vessels. The normal pH of blood is 7.35-7.45 in a healthy individual. There are buffers that regulate the pH. About 8 percent of a person’s body weight is blood, accounted for by a volume of blood being 4-6 liters (higher in males).

PLASMA COMPONENTS Most of the components of plasma are plasma proteins. There are some proteins that are unique to plasma and some that are found in other tissues. The proteins you should know include: •

Albumin—this protein has the highest concentration in the plasma. Albumin is a binding protein that transports steroids, fatty acids, and other non-hydrophilic substances. It is the main protein contributing to the osmotic pressure inside blood vessels, keeping water within the vessels. Accounting for about 54 percent of protein in the plasma, a normal level is about 3.5-5.0 g/dL in the blood plasma.

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Globulin proteins—this is the second most common type of protein in the plasma. Alpha and beta-globulins can transport lipid-soluble vitamins, fatty acids and other lipids, and iron in the bloodstream. Gamma globulins are important for the immune system. They contribute to the osmotic pressure to a lesser degree than albumin. Globulins account for 38 percent of the total plasma protein volume.

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Fibrinogen—this is made by the liver and contributes to blood clotting. It accounts for just seven percent of the total plasma protein volume in the blood. 225

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Hormone proteins—these are much less common than other proteins in the bloodstream. They account for a small percentage but are important for the endocrine system.

Proteins make up the bulk of what’s in plasma but there are other things as well. These include oxygen, carbon dioxide, many different ions, vitamins, glucose, metabolic waste products, and amino acids. These things together make up about 1 percent of the plasma volume.

FORMED ELEMENTS IN BLOOD These mainly include the cells we’ve already mentioned. A few of these elements (such as memory cells) can live a long time in the immune system but most of these cells last only a short time. This means that they must be continually replenished by the bone marrow. The process of making new blood when blood is lost or needs replacing is called hemopoiesis or hematopoiesis. This process happens mainly in the spongy bone tissue, where the bone marrow is located (but it can theoretically happen in the spleen and liver as well). All of these formed elements come from stem cells that retain the ability to form many different types of cells. These cells divide and one daughter cell goes on to become differentiated. There are several types of stem cells: totipotent stem cells (that can make any type of cell), pluripotent stem cells (that can make many but not all types of cells), and hemopoietic stem cells (that only make blood-related cells. These are also referred to as hemocytoblasts. These cells can be exposed to hemopoietic growth factors that allow them to make other types of blood cells. Hemocytoblasts can make one of two cell types: •

Lymphoid stem cells—these make lymphocytes, such as NK cells, B cells, and T cells. Each of these is an immune cell. They are only partially differentiated in bone marrow in some cases. While B cells mostly mature in bone marrow, T cells will finish the maturation process in the thymus.

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Myeloid stem cells—these make RBCs, myeloid cells (granulocytes, eosinophils, basophils, monocytes), and megakaryocytes (that make platelets).

As mentioned, there are growth factors that play a role in the development of these cells. For RBCs, the main growth factor is erythropoietin or EPO. This is a hormone secreted by fibroblast cells in the kidneys when they sense low oxygen tension. EPO goes to the bone marrow and triggers the division of myeloid stem cells to make cells along the RBC or “erythrocyte” line. This hormone is used in many medical situations that lead to reduced RBC counts in the body. Another growth factor is thrombopoietin, which is a glycoprotein hormone that makes megakaryocytes/platelets. It is produced by the kidneys and liver. Cytokines are made by many cells of the body and can act locally to stimulate the proliferation of cells to make more WBCs. The two subtypes of cytokines include colony-stimulating factors and interleukins. Colony-stimulating factors act completely locally to trigger myeloblasts to make neutrophils, basophils, and eosinophils. These are called “granulocyte CSFs.” They are used medically for cancer patients to increase the WBC count. Interleukins are signaling molecules made by several cell types to encourage the maturation of cells during inflammation and the immune response. There are many different interleukin types.

ERYTHROCYTES The erythrocyte, or RBC, is the most common formed element in the blood. These cells make up one-fourth of the total number of cells in the body. These are very small cells because they need to squeeze through tiny capillaries to give oxygen to the tissues. They pick up nearly all the oxygen in the lungs, carrying it to tissues; they only pick up 24 percent of the carbon dioxide, however. They do not leave the vessels (unlike WBCs, which extravasate out of the vessels). Erythrocytes mature in the bone marrow and lose their nucleus in the process. Immature RBCs are called reticulocytes and account for 1-2 percent of the total RBC count. The cells cannot use cellular respiration because they don’t have mitochondria and utilize anaerobic respiration in order to function. They have a unique structure, called the biconcave disc, which defines these cells. The main protein in the cell is oxygen-carrying hemoglobin. The shape gives it a greater 227

surface area for oxygenation of the tissues. They flex to fit in tiny capillaries. Figure 85 shows the shape of the erythrocyte:

Hemoglobin is the major protein in the erythrocyte. There are four folded chains that make up the molecule—each of which is bound to a molecule of iron and each of which takes up one oxygen molecule. Because of the numbers of hemoglobin molecules per cell are large (300 million molecules per cell), about 1.2 billion oxygen molecules can be transported per cell. Bright red blood contains oxyhemoglobin, while dark red blood contains deoxyhemoglobin (no oxygen attached to the molecule). When CO2 attaches to hemoglobin, it is called carbaminohemoglobin. An excess of RBCs is called polycythemia, which is a problem because it causes blood that is too viscous to circulate. A low number of RBCs leads to low hemoglobin levels, resulting anemia. Doctors can also measure the percentage of hemoglobin molecules that carry oxygen—a number called the “percent saturation” or “O2 sat” level. Low oxygen readings in the blood (a low O2 sat level) is called hypoxemia. Conditions of hypoxemia lead the kidney fibroblasts to secrete erythropoietin to make more RBCs. There are several nutrients necessary for the production of 2 million RBCs per second. Iron is the most important trace mineral that must be there for hemoglobin production. Ferritin and hemosiderin are the storage molecules for iron. Copper is also necessary for hemoglobin

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production. It helps make proteins that oxidize iron so it can help the iron transport protein (transferrin) be active and functional in transporting iron for heme production. Zinc is a coenzyme in the synthesis of hemoglobin so it is also necessary. The two B vitamins (folate and B12) are co-enzymes that facilitate the DNA synthesis necessary for making new RBCs. RBCs live 120 days in the circulation before being destroyed by macrophages. The globin part of hemoglobin gets broken down completely, iron gets recycled, and a waste product gets formed, called bilirubin. This molecule is used in the production of bile. The bile gets broken down in the GI tract by bacteria, leading to its elimination as stercobilin in the feces. Kidneys will also secrete byproducts of hemoglobin destruction (urobilin) in the urine.

LEUKOCYTES The leukocyte or WBC are involved in the body’s immune reponse. They originate from precursor cells in the bone marrow, with numbers about 5000-10,000 cells per microliter in the blood. They have nuclei and organelles (unlike RBCs) and there are several different types—all with a relatively short lifespan. They operate by leaving the blood vessels to act in the tissues. This process of leaving the vessel is called diapedesis, in which they squeeze out of the blood vessel wall. There is the process of chemotaxis, which is a signaling system that “calls” WBCs to sites where they are needed. There are two broad categories of leukocytes: Granular leukocytes (which contain granules) and agranular leukocytes (which don’t contain granules). Granular leukocytes come from the myeloid cell line, while agranular leukocytes come from the lymphoid cell line.

These cells are known as follows: •

Neutrophils—this is the most common leukocyte, with granules that stain “neutrally” under the microscope. It has a multi-lobed nucleus with older nuclei having more lobes over time. These are bacterial phagocytes, with granules that secrete lysozyme that can break down cell walls, hydrogen peroxide, and defensins (which puncture bacterial cell membranes).

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Eosinophils—these contain granules that stain with a stain called eosin. It has a 2-3lobed nucleus and granules that are red to orange in color. The granules contain antihistamines and things that are toxic to parasitic worms. Their count is elevated in worm infestations, certain autoimmune diseases, and allergies. They can phagocytize pathogens.

•

Basophils—these are the least common leukocyte (less than one percent of total leukocytes) and stain with basic stains. They have large granules that stain dark blue and a bilobed nucleus. They are increased in the inflammatory response and release histamines that contribute to inflammation and heparin, which blocks blood clotting. High counts are seen in low thyroid conditions, parasitic infections, and allergies.

Agranular leukocytes have less-visible granules in their cytoplasm and have a simpler nucleus. There are types of agranulocytes. These include lymphocytes and monocytes: •

Lymphocytes are derived from lymphoid stem cells and mature in lymphoid tissues. These are the second most common leukocyte in the blood. The three main types of lymphocytes are NK cells, B cells, and T cells. NK cells will recognize non-self cells (foreign cells, cancer cells, or virally-infected cells), providing nonspecific immunity. These are large lymphocytes. B lymphocytes and T lymphocytes also play a role in immunity. B cells make antibodies and T cells provide cellular immunity. Memory cells retain the memory of a previous pathogen and can be either T cells or B cells. They live for many years. High levels are seen in certain cancers and viral infections.

•

Monocytes come from the myeloid line and are quite large with horseshoe-shaped nuclei. These turn into phagocytes that kill debris, pathogens, and dead or damaged cells. They also attract other leukocytes to the site of an infection. High counts are seen in viral or fungal invasions, certain leukemias, and tuberculosis.

PLATELETS Platelets are small cell fragments that break off from megakaryocytes. They descend from the myeloid cell line. Megakaryocytes have very large, multi-lobed nuclei that come from megakaryoblasts under the influence of thrombopoietin. These cells do not leave the bone 230

marrow and simply release platelets into the circulation—about 2-3 thousand platelets per cell. There are about 150,000 platelets per microliter of blood. They participate in the clotting of blood, living about 10 days in total. Platelets will see exposed connective tissue when a vessel ruptures. This causes them to become sticky and spikey so that they stick together, binding to the endothelial lining and to exposed collagen fibers. This is aided by a blood clotting factor called von Willebrand factor, which stabilizes the plug of platelets. They release serotonin to constrict the blood vessel, ADP to help platelet adherence, and prostaglandins and phospholipids, to maintain the vasoconstrictive process. They are temporary measures to stop the bleeding process. Fibrinogen in the blood will form a mesh-like clot of fibrin that continues to stop excessive bleeding.

BLOOD CLOTTING PROCESS The clotting process involves coagulation factors or clotting factors. This is a complicated process with two main pathways: the extrinsic pathway (triggered by a traumatic event) and the intrinsic pathway (triggered by internal vessel wall damage). Ultimately, there is a common pathway that ends the clotting process. The clotting process involves 12 clotting factors made in the liver and by platelets. Many of the clotting factors require vitamin K as part of their synthesis. The extrinsic pathway is faster and a more direct pathway to clotting. It acts in traumatic injury situations and requires tissue factors. The intrinsic pathway is lower and more complicated. It requires bloodstream factors and a long coagulation pathway. The common pathway uses fibrin and involves turning the inactive prothrombin into thrombin (an active clotting enzyme) that stabilizes the fibrin clot. The clot eventually needs to break down so that a scar can form and healing can take place. This happens in the process of fibrinolysis, which takes the inactive enzyme plasminogen and turns it into plasmin, an enzyme that breaks down the fibrin clot. The vasodilator, bradykinin, is released so that normal circulation is restored.

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BLOOD TYPING A study of blood typing involves a study of antigens. Antigens are molecules on the surface of the cell that identifies the cell as being of a certain type. They are found on the surface of cells in order to say what the cell type is like. They bind to antibodies in certain situations, triggering the immune process that can result in the destruction of the cell. In blood typing, antigens are the molecules on the cell surface that define a cell as belonging to the self so that it isn’t acted on by the immune system. There are more than 50 antigens on RBC surfaces, with the ABO blood group and the Rh blood group being the most important ones. ABO blood group is actually just made from two antigens, called A and B. These are glycoproteins expressed on the surface of the antigen. A person can be type A or type B (with one of these antigens on their surface), or they can be type AB (with both antigens on the cell surface). The most common type, however, is called type O, with neither antigen on the surface of the RBC. These are genetically-determined with a person inheriting these antigens from their parents. Generally, people with a certain antigen will not be able to take blood from people with different antigens on their RBCs. This is because they will create antibodies against the antigen they lack. The Rh antigen is just one antigen. It is called the D antigen. If a pregnant mother does not have this antigen but has a fetus who has the antigen, they might make antibodies against the fetus’s red blood cells, potentially killing the fetus. Individuals who do not have the antigen cannot receive blood from individuals who have the antigen. About 85 percent of people are considered Rh-positive. It is distinct from the ABO antigens must be known before receiving transfused blood.

ARTERIAL BLOOD PRESSURE Arterial blood pressure is what’s measured in the arteries as the resistance to blood flow in the arteries as it flows through the vessels. It is measured in several ways. When the systemic arterial blood pressure is traditionally measured, it is recorded as a ratio of two numbers (the systolic blood pressure over the diastolic blood pressure). The systolic pressure is usually 120 232

millimeters of mercury (expressed as mm Hg) and the diastolic blood pressure is usually 80 mm Hg in the healthy person. They represent the blood pressure during contraction of the heart and the blood pressure during relaxation of the heart, respectively. The pulse pressure is the difference between the systolic and diastolic blood pressure, which should be about 25 percent of the systolic blood pressure. A low pulse pressure is described as being “narrow.” A narrow pulse pressure can be seen in aortic stenosis, congestive heart failure, and blood loss/low blood volume. A wide or high blood pressure can be seen after strenuous blood pressure in healthy people. Chronically high pulse pressures can cause organ damage. The mean arterial blood pressure or MAP is the average blood pressure in the arteries, it is a complicated number that must be calculated. A normal MAP is about 70-110 mm Hg; a low MAP means the possibility of low blood flow and ischemia to the organs and tissues. The blood pressure is measured (usually) by checking the pressure in the upper arm using a sphygmomanometer, which measures the pressure on a measuring device and uses a stethoscope to listen to Korotkoff sounds, which are sounds created by turbulent flow in the artery when the cuff is deflated. The pressure when the Korotkoff sounds begin is called the systolic blood pressure, while the blood pressure when the Korotkoff sounds end is the diastolic blood pressure. Things that affect the blood pressure and blood flow to the rest of the body include cardiac output, compliance of the arterial walls, blood volume, blood viscosity, and blood vessel length and diameter.

REGULATION OF THE CARDIOVASCULAR SYSTEM Blood pressure must be sufficient to provide adequate blood to the tissues on a continual basis. During exercise, blood flow is preferentially directed to the skeletal muscle, lungs, and heart. After a meal, blood flow is preferentially directed to the digestive system. The only organ that continually receives blood regardless of the situation is the brain. Blood must go to the skin during exercise as well in order to dissipate the generated body heat.

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There are three things that ensure adequate blood flow and sufficient perfusion to the tissues. These are neural regulation, endocrine input, and autoregulatory mechanisms.

NERVOUS SYSTEM IMPACT ON THE CARDIOVASCULAR SYSTEM The nervous system’s role involves cardiovascular centers in the brain that control cardiac and vascular functioning. The limbic system and emotions also play neural roles in determining blood pressure. Cardiovascular centers already discussed are located in the medulla. They respond to several aspects of the blood, including the blood pressure, oxygen concentration, hydrogen ion concentration, and carbon dioxide concentration. The cardioaccelerator centers stimulate the heart to pump faster and more forcefully. The cardioinhibitory centers decrease heart rate and stroke volume via the vagus nerve. Vasomotor centers in the brain control blood vessel tone in the muscle layer (the tunica media) in the arteries, which affect the blood pressure and cardiac output. There are baroreceptors (specialized stretch receptors) within the heart and some blood vessels that respond to the degree of stretch in the tissues. They send impulses to the cardiovascular centers in the medulla to help regulate blood pressure. They aortic sinuses also play a role, as they are located in the proximal aorta above the heart that respond to stretch. There are also stretch receptors (baroreceptors) in the carotid sinuses at the base of the internal carotid arteries. The vena cava and the right atrium have low-pressure baroreceptors. There is parasympathetic input in high blood pressure situations and sympathetic input in low blood pressure situations that regulate the blood pressure. There are chemoreceptor reflexes that monitor oxygen, pH (hydrogen ion concentration), and carbon dioxide levels that stimulate the cardiovascular and respiratory center in the medulla. These are located in the carotid and aortic sinuses near the baroreceptors. An active body will cause more acids to accumulate as waste products, more CO2 produced, and lower O2 levels. When this happens, the heart rate is increased and peripheral vessels are constricted, increasing the cardiac output.

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ENDOCRINE SYSTEM IMPACT ON THE CARDIOVASCULAR SYSTEM The endocrine control over the cardiovascular system involves mainly epinephrine and norepinephrine secreted by the adrenal medulla of the adrenal gland. They will increase the contractile force of the heart, constrict the blood vessels to certain organs, and increase the heart rate. Additionally, antidiuretic hormone (ADH) secreted by the hypothalamus and released by the posterior pituitary gland will help restore the blood pressure and blood volume in situations where there is a loss of blood volume. Renin secreted by the kidneys in response to low blood flow will increase blood pressure by making angiotensin I (which turns into angiotensin II) in the lungs. The end result is vasoconstriction and a marked increase in blood pressure. Angiotensin II also turns on aldosterone to increase the blood volume by taking up more water and sodium by the kidneys.

AUTOREGULATION OF THE CARDIOVASCULAR SYSTEM Autoregulation mechanisms are local mechanisms independent on the nervous system and endocrine control. There are chemical signals and myogenic controls over blood flow and blood pressure. There are chemical signals operating at the precapillary sphincters in the small arteries (arterioles) that will trigger vasoconstriction or relaxation of the blood vessels. This will locally regulate the blood flow to a specific tissue. There is also a myogenic response involving the stretching of smooth muscle in the walls of the small arteries (arterioles). It protects the tissues against wide fluctuations in blood flow and blood pressure to a specific tissue. In low blood pressure situations, the vessel will dilate to increase flow to the tissue. If blood flow is too high, there is decreased blood flow to the tissues by vasoconstriction of the arterioles, which prevents damage to the fragile blood vessels from too high flow to these tissues.

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PULMONARY CIRCULATION The pulmonary circulation is different from the systemic circulation. Blood returns from the body through the right atrium and enters the pulmonary circulation after being pumped out of the heart by the right ventricle. This blood is relatively deoxygenated and is headed toward the lungs in what is called the “pulmonary circuit.” The pulmonary circuit leaves the heart as the pulmonary trunk through the pulmonic valve of the right ventricle. It quickly divides into the left pulmonary artery and the right pulmonary artery. These branch further and further until they reach the pulmonary capillaries, which surround the alveoli of the lungs (where gas exchange occurs). After gas exchange has occurred, the blood flows through small venules and finally into four pulmonary veins. The pulmonary veins provide oxygenated blood to the left atrium, ending the circuit.

SYSTEMIC ARTERIES All of the systemic circulation begins with the aorta, which exits the left ventricle through the aortic semilunar valve. The aorta is the largest artery in the body, ending in the abdominal area and becoming two common iliac arteries. There is an ascending aorta that rises upward, an aortic arch that causes a reversal of the aortic flow, and a descending aorta, which enters the abdomen. The ascending aorta is about five centimeters in length. The descending aorta enters the abdomen through the aortic hiatus. The thoracic aorta is above the aortic hiatus, while the abdominal aorta is below the aortic hiatus. Figure 86 shows the arteries of the body:

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ASCENDING AORTA AND AORTIC ARCH BRANCHES The first vessels to branch off the ascending aorta are two coronary arteries, the left and the right coronary arteries. They arise from the aortic sinuses, which are dilations of the aorta. There is a third sinus that does not yield a blood vessel. The coronary arteries encircle the heart and branch off as described in Chapter 9 of this course. Other major branches occur in the aortic arch: the left common carotid artery, the brachiocephalic artery, and the left subclavian artery. The brachiocephalic artery is just on the right; it divides into the right subclavian artery and the right common carotid artery. While the left side comes directly off the aorta, it otherwise follows the same pathway as the right side. Each subclavian artery sends branches that supply the arms, chest, back, shoulders, and brain. The three main arteries that branch off of these are the internal thoracic artery (mammary artery, that supplies the pericardium, thymus, and anterior chest wall), the vertebral artery (to the back of the brain and spinal cord), and the thyrocervical artery (to the thyroid, neck, and upper back and shoulders). The common carotid artery divides into an external carotid artery (to supply much of the face, jaw, neck, and esophagus) and an internal carotid artery (which has a sinus containing chemoreceptors and baroreceptors). The internal carotid artery goes to supply much of the anterior aspect of the brain. Remember that the vertebral and internal carotid arteries connect (anastomose) and form a ring called the circle of Willis that supplies the brain.

THORACIC AND ABDOMINAL AORTA BRANCHES There are several branches off the thoracic descending aorta. There are visceral branches, including the pericardial arteries, bronchial arteries, esophageal arteries, and mediastinal arteries, which deal with internal body parts. The parietal branches deal with more external body parts, such as the intercostal arteries and the superior phrenic artery, which supplies the diaphragm.

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After crossing through the aortic hiatus to become the descending abdominal aorta, it lies to the left of the vertebral column. Its main branches are the celiac trunk (which divides into the left gastric artery for the stomach, the splenic artery for the spleen, and the common hepatic artery to the liver). The common hepatic artery sends branches to the stomach (right gastric artery), the liver proper (the hepatic artery proper), and the gallbladder (cystic artery). Beneath the celiac trunk, there is the superior mesenteric artery (to the small intestine) and the inferior mesenteric artery (to the distal large intestine and rectum). There are paired arteries (the inferior phrenic artery to the diaphragm, the adrenal artery to the adrenal glands, and the renal artery to the kidneys). There are branches, too, that lead to the ovaries (the ovarian artery) and the testicles (the testicular artery). There are four lumbar arteries that supply blood to the lumbar region, spinal cord, and abdominal wall. These, too, are paired. The aorta ends at the L4 vertebrae as the left and right common iliac arteries. The median sacral artery is the continuation of the aorta to the sacrum. The common iliac artery provides blood to the pelvis and lower limb. The internal iliac artery sends arteries to the external genitalia, pelvic walls, bladder, vagina, and uterus. The external iliac is the vessel that supplies blood to each limb.

UPPER LIMB ARTERY The subclavian artery becomes the axillary artery as it exits the thoracic cavity. It supplies branches to the head of the humerus but continues for the most part as the brachial artery in the upper arm and elbow. This divides into the radial and ulnar arteries, which go onto the forearm down the radial and ulnar sides of the forearm, respectively. The palmar and digital arteries branch off from these arteries to supply the hand. Figure 87 shows the major vessels of the upper arm:

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ARTERIES SERVING THE LOWER LIMBS The external iliac becomes the femoral artery after it exits the trunk. There is the deep femoral artery that gives rise to the lateral circumflex artery to supply the deep thigh muscles. The genicular artery comes off the femoral artery to supply the knee area. The femoral artery becomes the popliteal artery at the level of the knee. There are the anterior and posterior tibial arteries that supply the lower leg and the foot. The anterior tibial artery becomes the dorsalis pedis artery on the top of the foot. The posterior tibial artery provides blood to the posterior calf. It splits to become the medial plantar artery and the lateral plantar artery, supplying the bottom of the foot. Figure 88 shows the major arteries of the leg:

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VEINS: ANATOMY AND PHYSIOLOGY All systemic veins return blood via the superior vena cava and the inferior vena cava to the right atrium. The blood is low in oxygen. The veins largely travel along the same pathways as the arteries and are named in figures 87 and 88. There are deep veins of the head and neck that correspond to major arteries; however, the same cannot be said of superficial veins. Veins in general will regulate the temperature of the body by dilating and by having blood diverted to superficial veins that relieve the body of heat.

UPPER BODY VEINS The superior vena cava drains the upper body. There are subclavian veins, axillary veins, and vertebral veins that match the corresponding arteries. There are paired internal thoracic veins that drain the anterior chest wall. The azygous vein drains a large amount of blood from the thorax. There is a small hemiazygos vein that also drains blood from the thoracic region. It drains into the brachiocephalic vein in the chest. Figure 89 shows the major veins in the thorax:

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The head and neck veins all flow into either the internal jugular vein (from the brain and superficial facial vein) or the external jugular vein (from the scalp, head, and cranial areas). The external jugular vein empties into the subclavian vein in the chest. The internal jugular vein follows the common carotid artery. The brain veins are actually sinuses that drain the CSF and blood from the brain. The major sinus in the brain is the superior sagittal sinus. It drains the CSF via the chorionic villi (arachnoid granulations) along the outside surface of the brain. Lesser sinuses are the straight sinus, occipital sinus, the cavernous sinus, transverse sinus, the sigmoid sinus, and the petrosal sinus. These drain into the internal jugular vein. The upper limb drains start with the digital veins that lead to the palmar venous arches, the radial vein, the ulnar vein, and the brachial vein (which parallels the brachial artery). The brachial vein drains into the axillary vein. The medial cubital vein is a superficial vein where blood is often taken in the antecubital area (in the inner elbow area); it comes from the median antebrachial vein. The basilic vein is located in the forearm and becomes the axillary vein. Figure 90 shows the veins of the upper arm:

There is also a cephalic vein, which is superficial in the upper arm that leads to the axillary vein. The axillary vein is the main vein of the upper extremity. It ultimately becomes the subclavian vein in the thorax. This empties into the venous system of the superior vena cava. 244

VEIN DRAINAGE IN THE LOWER BODY The inferior vena cava drains much of the blood below the diaphragm. The vein parallels the abdominal aorta for the most part and drains a number of lumbar veins (which drain the abdominal wall). There are renal veins, adrenal veins, testicular veins, ovarian veins, and phrenic veins that are similar to their arterial counterparts and draining parts of the interior of the abdomen and pelvis. There is a hepatic vein that drains the liver, entering into the inferior vena cava. There are veins that drain the lower limbs, starting with the plantar veins on the arch of the foot and the digital veins. They form a complex dorsal venous arch and plantar venous arch in the top and bottom of the foot, respectively. In the lower leg, there are two branches, the anterior and posterior tibial veins. These ultimately drain into the popliteal vein in the back of the knee. This becomes the femoral vein in the thigh. The femoral vein becomes the external iliac vein in the lower trunk area, joining the interior iliac vein (which drains pelvic structures) to become the common iliac vein. The two common iliac veins form the inferior vena cava.

HEPATIC PORTAL SYSTEM The liver has its own “portal system.” It is a major processing plant in the digestive system, responsible for taking absorbed nutrients and processing them. It also makes bile, clotting factors, and plasma proteins. The portal system starts with the capillaries of the stomach, small intestine, spleen, and large intestine. The blood ultimately ends in specialized capillaries within the liver, called the hepatic sinusoids. Larger structures include the hepatic portal vein that forms from the superior mesenteric, inferior mesenteric, and splenic veins. It adds blood from the cystic veins (the gallbladder veins) and the gastric veins (from the stomach). These veins contain a great many nutrients that go to the liver for processing. This means that the liver receives blood from the hepatic artery and the hepatic portal vein.

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KEY TAKEAWAYS •

The blood contains plasma and multiple formed elements.

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All formed elements come from hematopoietic stem cells.

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There are cells from the myeloid stem cells and cells from the lymphoid stem cells.

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The blood pressure is the amount of force generated by the heart in the blood vessels, both in systole and in diastole.

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The largest artery in the body is the aorta, while the largest veins are the inferior and superior vena cava.

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The veins mostly follow the arteries in the circulatory system.

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QUIZ 1. What component of blood makes up the greatest amount in volume? a. RBCs b. WBCs c. Platelets d. Plasma Answer: d. About 53-59 percent of the blood by volume is the plasma, with the next greatest amount by volume being RBCs. 2.

Which protein has the highest concentration in the blood plasma? a. Albumin b. Fibrinogen c. Gamma globulins d. Alpha globulins Answer: a. Albumin is extremely common, accounting for more than half of the plasma proteins in blood plasma.

What hematopoietic growth factor is used to increase the RBC count in certain cases of anemia? a. Thrombopoietin b. Cytokines c. Erythropoietin d. Colony-stimulating factor Answer: c. Erythropoietin is the stimulating growth factor for the development of red blood cells in the human body. It is made by the fibroblasts in the kidneys and is decreased in cases of kidney failure.

Low levels of oxygen in the bloodstream is known as what? a. Hypoxemia 247

b. Polycythemia c. Anemia d. Hyperbilirubinemia Answer: a. Hypoxemia is a low level of oxygen in the bloodstream. It can be caused by many reasons and will result in a low oxygen saturation level or a low O2 sat level. 5.

Which leukocyte type is responsible for bacterial phagocytosis and is elevated in bacterial infections? a. Neutrophils b. B lymphocytes c. Eosinophils d. Monocytes Answer: a. Neutrophils are responsible for bacterial phagocytosis. Their numbers are increased in bacterial infection.

Which type of leukocyte makes antibodies in the face of infection? a. Neutrophils b. B lymphocytes c. NK cells d. Monocytes Answer: b. B lymphocytes are responsible for making antibodies in response to an infection. The antibodies are specific to a particular infection.

The top number obtained when measuring the blood pressure is called what? a. Pulse pressure b. Mean arterial blood pressure c. Diastolic blood pressure d. Systolic blood pressure

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Answer: d. The systolic blood pressure is the pressure obtained when the blood pressure is measured. 8.

Blood pressure is partially determined by the presence of baroreceptors in the body. Which is not a place where baroreceptors are located? a. Right atrium b. Left ventricle c. Aortic sinuses d. Carotid sinuses Answer: b. There are baroreceptors that detect high and low stretch in the vessels. They are located in each of these areas but not in the left ventricle. There are also low pressure stretch receptors in the vena cava.

Which major artery does not directly come off the aorta? a. Left subclavian artery b. Brachiocephalic artery c. Right subclavian artery d. Left common carotid artery Answer: c. The right side of the aortic arch gives rise to the brachiocephalic artery that divides into the right subclavian and right common carotid artery. These do not directly come off the aortic arch.

10.

Which is the major artery going to the arms? a. Common carotid artery b. Subclavian artery c. Brachiocephalic artery d. Vertebral artery Answer: b. The left and right subclavian arteries send branches to supply both arms.

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CHAPTER ELEVEN: LYMPHATIC AND IMMUNE SYSTEM The lymphatic system includes the vessels of the lymphatic system that filter blood and pathogens, making these structures also important to the immune system. The thymus gland is a part of the immune system as well as the spleen. Both of these are discussed in this chapter. The immune system is broadly divided into the innate and adaptive immune system. The cells of the immune system and the physiology of these aspects of the immune system are explained in detail in this chapter.

ANATOMY AND PHYSIOLOGY OF THE LYMPHATIC SYSTEM The lymphatic system is responsible for draining body fluids from the periphery, sending it back to the bloodstream. The pressure of blood on the vessels causes a leakage of fluid from the capillaries, which causes an accumulation of fluid into the spaces between the cells. About 20 liters of plasma enters the interstitial space from capillary filtration. It is then that it is called “interstitial fluid.” About 17 liters gets reabsorbed back into the bloodstream, leaving three liters per day that needs to get back into the circulation as lymph fluid. Lymph is protein-rich fluid that travels through lymph vessels. In some cases, it backs up and does not function the way it is supposed to. This leads to a condition called lymphedema. Lymph vessels are also used to transport immune cells from one place to another as well as to transport lipids and fat-soluble vitamins through the body. Lymph nodes are organs of both the lymphatic system and the immune system as they become areas where immune responses take place. Lymph vessels start as open-ended capillaries that feed into larger and larger lymphatic vessels, which ultimately empty into the blood stream via several lymphatic ducts. The lymph travels through multiple lymph nodes, located in the groin, chest, neck, axillae, and abdomen. There are about 500 lymph nodes in the entire body.

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Lymph vessels contain lymph that is not passed through the vessels by actions of the heart pumping; instead, it is forced through the vessels because of contraction of the body’s skeletal muscles as well as from the act of breathing. There are semi-lunar valves or one-way valves in the lymphatic vessels that prevent backflow of lymph fluid. The fluid travels from smaller vessels to larger ducts that enter the bloodstream via ducts that empty at the junction between the jugular and subclavian veins in the neck. The lymphatic capillaries or “terminal lymphatics” are located in the body tissues and interlace with the small arteries and veins of the circulatory system. They are not found in the cornea, bones, bone marrow, or teeth but are found in all other body tissues. These are one cell-thick layered vessels that allow interstitial fluid to flow into them. There are endothelial flaps that open only when the hydrostatic pressure in the tissues is high so fluid can enter the capillaries. In the small intestine, these lymphatic capillaries are called lacteals. They take up a fluid called chyle, which contains fat-soluble vitamins and dietary lipids from the intestinal tract to the lymphatic system. The chyle first enters the liver and then goes into the bloodstream. Larger lymphatic vessels are similar to veins, having a three-layered structure and valves. The valves are located close to one another to keep lymph going through the system. Larger lymph vessels are also known as lymphatic trunks. The right upper side of the body drains fluid into the right lymphatic duct and into the right subclavian vein. The left side of the body and the lower half of the body drains into the thoracic duct, which drains into the left subclavian vein. The thoracic duct receives blood from the lower limbs and lower abdomen and begins with the cisterna chyli (a dilated chamber that receives lymph) in the upper abdomen.

THE IMMUNE SYSTEM The immune system is large and involves multiple things that interact with one another in order to fight pathogens. The three main components in the immune system (which act in a temporal fashion) include the following:

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Barrier mechanisms—these include the mucous membranes, skin, and the GI tract, which all act as the first defense against pathogens, keeping them from entering the body.

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Innate immune system—this consists of certain cells that act in a nonspecific way in order to protect the tissues that have become invaded by pathogens.

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Adaptive immune system—this involves mainly WBCs that act in a controlled and specific way in order to kill diseased and cancerous cells, as well as specific pathogens.

There are three main types of cells that are involved in the immune system. Each of these cells arises from the hematopoietic stem cell line, which involves stem cells that continually divide and differentiate. The three cell types include the following: •

Phagocytes—these are various cells that ingest pathogens and cellular debris

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Lymphocytes—these are part of the adaptive immune system

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Mediator cells—these contain cytoplasmic granules that help mediate the immune response against intracellular pathogens and parasites

LYMPHOCYTE FUNCTION Lymphocytes play a major role in the adaptive immune system. There are two major lymphocyte types, including B and T lymphocytes. They morphologically look identical with very large nuclei. Both B and T cells can be found in the circulation, in lymph fluid, and in lymph organs (which are mainly the spleen and lymph nodes). B cells mainly produce antibodies. An antibody is a group of specific proteins that bind to pathogen-associated molecular structures called antigens. Most antigens can be found on the surface of a foreign pathogen, a foreign cell, or a dying cell. They are called antigens because they create an immune response by virtue of being considered “foreign.” B cells that are activate and are actively secreting antibodies are known as plasma cells.

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T cells do not secrete antibodies but secrete proteins and other factors that communicate with other cells of the immune system to kill intracellular pathogens and damaged cells. They work together with B cells as part of the adaptive immune system. Plasma cells are actively-secreting B cells that have the ability to bind to antigens and make more antibodies. They look different from ordinary B cells in that they have a large amount of rough endoplasmic reticulum and larger amounts of cytoplasm. Natural killer cells are participants in the innate immune system. These are lymphocytes that contain cytotoxic granules designed to kill cells. They act similarly to T cells but act more nonspecifically, acting as the first line of defense against some cancerous and virally-infected cells.

LYMPHOID ORGANS The two primary lymphoid organs are the bone marrow and the thymus gland. These are the main places for the development, proliferation, maturation, and selection of the different lymph cells. The bone marrow is of two types: the red and yellow bone marrow. Yellow bone marrow mainly stores fat, while red bone marrow is the site of hematopoiesis. This is where most of the B cell matures. T cells partially mature and are released as immature “thymocytes,” destined for further development in the thymus gland. The thymus gland is located in the upper anterior chest. There are two lobes to the structure that is held together by connective tissue. The gland is divided into lobules and consists of an outer cortex and an inner medulla. The cortex consists of many thymocytes and epithelial cells, as well as phagocytic cells (macrophages and dendritic cells). The natural selection of mature T cells progresses from the cortex to the medulla, with phagocytic cells destroying T cells that are not selected to be mature T cells. There are also secondary lymphoid organs involved in the maturation process of lymphocytes. Cells that leave the primary lymphoid organs are called naïve lymphocytes. Naïve lymphocytes that do not yet have an encounter with an antigen are still potentially functional. They

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concentrate in the secondary lymphoid tissues, which are lymphoid nodules, lymph nodes, and the spleen. Lymph nodes remove pathogens and cellular debris from the lymph fluid, essentially filtering the lymph. There are dendritic cells and macrophages within lymph nodes that kill off bacteria and other pathogens. Lymph nodes are sites of adaptive immune processes, requiring B cells, T cells, and other immune cells. There is a capsule surrounding the lymph node with extensions called trabeculae that separate the node into different germinal centers. Entering into the lymph node are afferent lymphatic vessels that bring the fluid into the node. Leaving the lymph node are efferent lymphatic vessels, carrying cells and cleaned fluid. The fluid that enters the lymph node goes into a subcapsular sinus, containing dendritic cells, reticular fibers, and macrophages. The cortex of the node has lymphoid follicles. These follicles have germinal centers that have rapidly dividing B cells surrounded by a layer of T cells and other cells that help in the process. Figure 91 is a picture of the microscopic anatomy of the lymph node.

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Lymph fluid flows from the afferent vessel to the subcapsular sinus, to the cortex, to the medulla and medullary sinuses, and to the efferent vessel, which is when the “cleaned” and filtered lymph fluid drains out of the node. Inside the lymph node, the B cells, plasma cells, and T cells act to destroy pathogens. The spleen is another secondary lymphoid organ. It is about five inches in diameter and is attached to the lateral aspect of the lymph node by the gastrosplenic ligament. There is a thick capsule in the spleen and extensive vascularization inside the organ as it acts to filter a great deal of blood. Like other lymphoid organs, there are macrophages and dendritic cells that eliminate dying or damaged RBCs and other material that is foreign to the body. Bloodborne pathogens, in particular, are eliminated by the cells in the spleen. Like related organs, there are trabeculae (connective tissue partitions) that separate the spleen into nodules. The nodule has “red pulp” consisting of RBCs and “white pulp” consisting of cells that are the same as are seen in the lymphoid follicles of lymph nodes. Blood enters the spleen via the splenic artery and divides into arterioles. Then the blood enters sinusoids and leaves through the splenic vein. Red pulp has reticular fibers that have fixed macrophages attached to them, free macrophages, and blood. White pulp surrounds the arterioles and is made from germinal centers of B cells and T cells, plus macrophages and dendritic cells. It is where adaptive T cells and B cells do their activity. Figure 92 is a description of what the spleen looks like:

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Lymphoid nodules are basically simpler than the spleen and lymph nodes but are sites of activity where immune function takes place. There is no fibrous capsule but only clusters of lymphocytes. There are clusters of lymphocytes located in the digestive tract and respiratory tract because these are areas that are most likely to be exposed to environmental pathogens. The tonsils are examples of lymphoid nodules and are located in the back of the mouth in the oropharynx. These are deeply invaginated so that they have a large surface area. The crypts or invaginations collect debris that can be turned into antigens that help in the defense of the different pathogens that are inhaled or swallowed, particularly by children. Mucosa-associated lymphoid tissue or MALT, which consists of a cluster of lymphoid follicles directly linked to mucous membranes. These are swellings seen under the mucosal linings of GI organs, lungs, eyes, and breast tissue. The small intestine consists of MALT called Peyer’s patches that act against ingested substances. They contain specialized M cells that take material in the intestinal lumen, transporting it to nearby lymphoid follicles in order to mount an adaptive immune response. On the other hand, there are bronchus-associated lymphoid tissues called BALT that consists of lymphoid tissue just underneath the epithelial layer in the bronchi where the bronchi bifurcate. These act like the tonsils to mount an attack against inhaled pathogens.

THE BARRIER MECHANISMS The first layer of defense in the immune system is the barrier mechanism, which is present throughout the body. These are present so that pathogens don’t get into the body in the first place. These are nonspecific and stop any type of pathogens. The skin is the major barrier to infection. It is considered too dry for pathogens and it sheds cells continuously, taking bacteria with it. The sweat in the skin will wash away pathogens and creates an acidic environment that is hostile to pathogens. Other defense mechanisms include the salivary glands in the mouth that secrete lysozyme that reacts against bacterial cell walls, the low pH in the stomach, and the mucosal epithelium on mucosal surfaces. Remember from the previous chapters that mucosal epithelium consists of 256

tight junctions that do not let pathogens get through. In addition, there are nonpathogenic bacteria on the mucosal surfaces that prevent the growth of pathogens. Respiratory surfaces will have cilia and mucus that trap bacteria and push them upwards out of the respiratory tract.

INNATE IMMUNE RESPONSES The innate immune system is a nonspecific aspect of the immune system. The most common role of the cells of the innate immune system is to phagocytize pathogens, debris, and infected tissues. This is a rapidly-acting line of defense against organisms that have made it past protective barrier mechanisms. The main cells of the innate immune system are phagocytes that destroy pathogens. In doing so, the phagocytic cell takes the organism in and encapsulates it in a phagosome, which fuses with the destructive lysosomes in the cell, forming a phagolysosome that kills off the pathogen. The major cells that do this are neutrophils, macrophages, and dendritic cells. Let’s look at these: •

Macrophages—these are cells that can move through tissues using their pseudopodia to get to damaged tissues. They can be fixed to reticular fibers in lymph nodes or can be freely roaming through tissues. These are the first line of defense against pathogens. They are called by different names, depending on where they reside. For example, in connective tissue they are called histiocytes; in the liver they are called Kupffer cells; in the lungs they are called alveolar macrophages.

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Neutrophils—this is a bloodborne phagocytic cell that is attracted via chemotaxis to infected tissues. They contain intracytoplasmic granules filled with histamine and other vasoactive mediators. They are called into the site of pathogens or an “infection” to do more than can be done by macrophages alone. They act in both the innate and adaptive immune systems.

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Monocytes—these are precursor cells that circulate in the blood and become a macrophage or a dendritic cell. Dendritic cells are tissue-resident phagocytic cells that participate in the innate immune system. These cells also act as antigen-presenting 257

cells, which mean that they “chew up” pathogens and present their surface antigens on their surface in order to initiate an adaptive immune response.

NATURAL KILLER CELLS These are lymphocytes that can cause programmed cell death, or apoptosis, of an infected cell. Usually, they act on cells that have intracellular bacteria or those that are infected with viruses. Exactly how the NK cell recognizes these cells isn’t completely clear. The NK cell actually induces another cell’s apoptosis by expressing a surface molecule known as a Fas ligand. It binds to the Fas molecule on the infected cell, sending a signal to kill the cell. Another way it can do this is through the release perforins (which make pores to kill infected cells) and granzymes (which digest proteins inside the cell, causing cell death) from the NK cell.

RECOGNIZING A PATHOGEN The question is how these innate immune cells can recognize that something is a pathogen. Basically, they have pattern recognition receptors or PRR that recognize molecules found on bacterial cell walls or other bacterial components. They recognize that a specific pathogen is not a part of the person and also recognize that a cell is damaged or under distress. These receptors were in place before the adaptive immune system developed and are relatively nonspecific. There are just a few PRRs on the cell surface that might react to a variety of pathogens. This is different from the adaptive immune system that has many different receptors that are specific to a particular pathogen. If the PRR binds to a certain pathogen, it will initiate phagocytosis or cellular apoptosis (if the pathogen is inside a damaged cell).

SOLUBLE FACTORS Both cytokines and chemokines are soluble factors. Cytokines are signaling molecules that allow for cell-cell communication over short distances. They are released by one cell to affect a

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nearby cell. A chemokine is a soluble chemical mediator that attracts cells over longer distances. They participate in chemotaxis, which attract cells to the site of an infection. Interferons are a part of the innate immune system. These are proteins that are released from virally-infected cells in order to send a signal to nearby cells, telling them to make antiviral proteins. Similar molecules that can do this include mannose-binding and C-reactive proteins. These are made by the liver and will bind to cell walls of bacteria; the end result is to bring phagocytes near the pathogenic bacteria. In addition, they participate in “opsonization,” which is tagging of pathogens by an antimicrobial protein (or an antibody), marking it for phagocytosis.

COMPLEMENT SYSTEM The complement system are soluble proteins that are found in blood plasma. They don’t act as part of the early immune response but are instead made in the liver. They act in the innate and adaptive immune systems through different pathways. These are a series of proteins and enzymes that form a reaction sequence that leads to one of the following: •

Opsonization of a pathogen so that it can be phagocytized.

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Attract phagocytic cells to the site of an inflammation.

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Cause pores in the plasma membrane of a pathogen, killing it.

INFLAMMATION IN THE IMMUNE SYSTEM The innate immune system involves an inflammatory response, which is the response that happens anytime the body is handling a pathogen. It can happen with an infection or tissue injury of any kind. The goal is to bring in phagocytic cells so that debris can be removed and repair can take place. It also limits the degree of infection so it stays at the original site. There is short-term inflammation and chronic and long-term inflammation or “chronic” inflammation. There are several processes that happen in an inflammatory response. These include the following:

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Tissue damage—injured cells cause mast cells to degranulate (release granules) containing histamine that causes vasodilation and increased blood flow, prostaglandins (leading to pain), and leukotrienes (that attract neutrophils).

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Vasodilation of vessels—this increases the heat to the affected area and leads to redness and increased tissue perfusion.

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Increased capillary permeability—this leads to swelling of the affected area.

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Cellular recruitment—phagocytes are recruited by leukotrienes, including neutrophils for the phagocytosis of the pathogens.

Inflammation will increase the ability of clotting factors to begin to heal the injury. The adaptive immune system is brought in to help eliminate the infection; the cells necessary for making the scar and healing the wound are also brought in by the inflammatory response.

THE ADAPTIVE IMMUNE SYSTEM The innate immune system is an older evolutionary system that does not work to handle specific pathogens. A newer way to kill pathogens is the adaptive immune system. It has a great deal of power in specifically identifying and killing various pathogens. It mainly involves recognizing antigens on pathogens as being foreign, making antibodies against the antigens, and destroying the pathogen because of its specific antigens. The first time there is exposure to the pathogen, there is a “primary adaptive response” and a sickness that is worse than any other future exposures to the pathogen. After the adaptive immune system has responded to the pathogen, the next time there is an infection, there is a “secondary adaptive response” in which there has been immunological memory that protects the individual from repeated infection from the initial pathogen. In such cases, there are few or no symptoms of an infection. The adaptive immune system has what’s known as self-recognition. It can tell the difference between self-antigens and nonself-antigens. This is a system that is not completely perfect as

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there are autoimmune diseases, in which a person makes antibodies and generates a response against a self-antigen, leading to disease that is not from a pathogen. The cells that take part in the adaptive immune system are the B and T cells. The T lymphocytes recognize antigens by having an alpha-beta T cell receptor on their surface. These are two-chain receptors with an alpha and beta chain. This receptor has a variable region, a constant region, and a transmembrane region (also called the anchoring region). There is one type of receptor per T cell that responds to a specific antigen.

WHAT IS AN ANTIGEN? An antigen is a specific pathogen generally a large protein molecule but can be another type of molecule. It consists of one or more epitopes, also called antigenic determinants, which are the regions where a receptor can bind. Epitopes can be small amino acid fragments or carbohydrate segments that are specifically recognized by an immune cell. T cells do not recognize the antigen directly on the pathogen. They only recognize the antigen that is “presented” to them on an antigen presenting cell. Intigen processing is when a phagocytic cell chews up a pathogen, processes it, and puts specific pathogenic antigens on their surface that are presented to a T cell. The antigen that is presented must be connected to a major histocompatibility complex or MHC. These allow the T cell to recognize the antigen as being foreign. Figure 93 is a picture of how an antigen presenting cell does this:

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There are two types of MHC molecules: MHC class I and MCH class II. Each of them acts in antigen presentation and participate in recognition by T cells. The main difference between the two are the types of cells they present the antigen to. The antigen is processed in the APC (antigen presenting cell) and gets fused to an MHC molecule. The fused molecule gets sent to the APC cell surface, where it is detected and read by a T cell. Most cells express MHC class I molecules when they present intracellular antigens. They stimulate a cytotoxic T cell that will destroy the cell plus the pathogen within it. This is the case with viral infections that can infect just about any cell of the body. MHC class II molecules are expressed only on certain immune cells. Specifically, they are only expressed on “professional antigen presenting cells.” The only professional APCs in humans are dendritic cells, B cells, and macrophages. Macrophages are professional APCs that stimulate T cells to release chemical messengers (cytokines) that make phagocytosis more effective. Dendritic cells bring antigens to nearby lymph nodes for presentation. T cells are within the nodes to receive the antigens and respond to them. B cells present antigens to T cells in order to generate an antibody response.

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T CELL DEVELOPMENT AND MATURATION T cells go through a process that helps make sure that the cell won’t attack normal cells and that it belongs to the cell. Mature T cells will express one of two different molecules on their surface: CD4 molecules indicate that the cell is a helper T cell (which “helps” the immune process), while CD8 molecules indicate that the cell is a cytotoxic T cell (which does actual cell and pathogen killing). In the thymus cortex, the immature T cells do not express either molecule. They are referred to as “double negatives.” These cells bind to the class I MHC molecules on the epithelium of the thymus in a process of positive selection. This makes sure the T cell belongs to the person’s body. Cells that cannot bind to the MHC I molecule are destroyed and phagocytized. The thymocytes or T cells, as they mature, will become “double positives” that will express both CD4 and CD8 on their surface. They move onto the medulla of the thymus, participating in “negative selection” This will involve the presence of a professional antigen presenting cell inside the thymus. The cell that can bind to the profession APC is destroyed because it means that it will fight off a self-cell, causing an autoimmune disease. This means that only two percent of the initial number of thymocytes leave the thymus as mature and functioning T cells. Ultimately, the cell that leaves the thymus gland is only going to be a single positive. The CD4 cell is a helper T cell that will bind to a class II MHC cell, while the CD8 cell is a cytotoxic T cell that will bind to a class I MHC. Mature T cells become activated by recognizing an antigen attached to the self’s MHC molecule, causing it to divide rapidly in a process called clonal expansion. This enhances the immune response. They have the ability to bind to a specific pathogenic antigen, which is called clonal selection. The cells that are made by an activated T cell are clones “identical” to the original cell. Some of the dividing cells will be “memory” T cells, which last a long time and retain the memory of the infection. Others will be “effector” T cells that will respond to the infection.

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Helper T cells or Th cells have the CD4 molecule in them. They secrete cytokines (chemical messengers). There are two types of Th cells. The Th1 cell makes cytokines that regulate the immune response by acting on other T cells and macrophages. The Th2 cell also secretes cytokines but these act on B cells so they can turn into plasma cells that make antibodies. T helper cells are necessary for most situations where an antigen goes on to make antibodies. Cytotoxic T cells or Tc cells do the actual killing of infected cells in the same way as NK cells do. They either express the Fas ligand (that binds to Fas receptors on infected cells) or make perforins and granzymes to cause apoptosis from within the cell. Regulatory T cells or Treg cells are also referred to as suppressor T cells. These have several molecules on their cell surface. The first is the CD4 molecule (making them similar to helper cells). The others are called CD25 and FOXP3. It is believed that they suppress clonal expansion so that the immune process does not go unchecked. It is a cell type that isn’t completely understood.

ANTIBODIES AND B CELLS Antibodies are also referred to as immunoglobulins. They are made by B cells in response to a specific antigen. They are actually receptors on B cells that get secreted into the blood stream in most cases. Some are not secreted but are called surface immunoglobulins on the B cell. There are five kinds of antibodies, called IgM, IgD, IgG, IgA, and IgE. Each antibody type acts slightly differently in the immune system that are effective in killing pathogens. Remember that B cells differentiate and mature mainly in the bone marrow. They undergo central tolerance, which is the destruction of any B cells that recognize self-antigens. Clonal deletion happens to immature B cells that bind too strongly to self-antigens (preventing the problem of self-antibodies). It causes these cells to die off. In clonal anergy, the same thing happens to the B cell; however, the B cell isn’t deleted but is unable to function. Remember, too, that mature B cells do not have the ability to make antibodies until they get the go-ahead from Th2 (helper T cells). If the B cell does not get a signal from the Th2 cell, it gets a signal to die and undergoes apoptosis. This is called peripheral tolerance. Once the B 264

cell gets a signal, it becomes a plasma cell, divides, and makes antibodies for a specific period of time before dying off. Only memory B cells (made during the differentiation process) are longlived and maintain a memory of the infection. Antibodies are made from heavy and light chains. Figure 94 shows what the different types of antibodies look like:

The heavy chain is what defines the type of antibody being talked about. The light chain forms part of the antigen-binding site. There are two identical heavy chains and two identical light chains with a Y-shaped antibody structure. The Fc region is the part of the two heavy chains that are connected to one another. It does not bind to the antigen. The light chain and part of the heavy chain are bound together in the upper part of the “Y” to form the antigen binding site (which binds to the antigen). There are two antigen binding sites per antibody molecule. The antibody can be bound to a B cell, making it a B cell receptor. It can also be secreted into the bloodstream as a free antibody. Mature B cells that leave the bone marrow can express

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both an IgM antibody and an IgD antibody. Of these, only the IgD stays on as a B cell receptor. These are the different types of antibodies made by B cells: •

IgM—this is a large antibody made from five different antibody segments, making a total of 10 identical antigen-binding sites. It is the first antibody made in response to an infection. It starts the process of fighting off the infection by activating the complement cascade. The B cell, however, can undergo “class switching,” making other types of antibodies to the same antigen.

•

IgG—this is a late response antibody that occurs after antibody switching. It is a single antibody that can eliminate pathogens in the bloodstream. It can cross the placenta, providing temporary “passive immunity” to the fetus and baby.

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IgA—this can exist as a four-chain or an eight-chain antibody. It is found in mucous membranes, acing on body surfaces. It is secreted in breast milk to prevent disease in infants and providing passive immunity (which is always temporary).

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IgE—this antibody is linked to allergies and to anaphylactic reactions. It causes degranulation of mast cells, which results in the allergic response, which can be severe.

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IgD—this is a poorly understood antibody expressed in immature B cells. It is accompanied by IgM cells and is both bound to the B cell as a B cell receptor and secreted by the B cell in small quantities. They seem to function in allowing the activation of the B cell to make other types of antibodies.

It takes several days for an antibody to be made against an infection, during which time, the person is usually sick from the infection. Then IgM antibodies are made, allowing for the ability to fight off the initial infection. Later, there is class switching so that the IgG antibody is made. The memory cells are present indefinitely, however, so the next time the pathogen is encountered, the B cells can proliferate so that the antibody can be directed and the person does not get sick, or as sick, with future exposure. Passive immunity involves giving a fetus the antibodies necessary to fight the infection OR to give a person some immunoglobulins to a specific infection so they don’t get sick from a known

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infection. This is temporary measure. Active immunity happens either when the person gets the infection and makes their own antibodies OR when the person gets an immunization and makes specific antibodies. Immunizations involve giving killed bacteria, killed virus particles, or “attenuated inactive viruses” that will initiate an immune response without actually having the real infection.

T CELL-RELATED ANTIGENS As mentioned, Th2 cells are important in causing B cells to make antibodies against a particular antigen. These are T cell-dependent antigens. There are also T cell-independent antigens that do not require a T helper cell to activate the B cell to make antibodies. In T cell-dependent activation, the B cell and T helper cell must come together for the B cell to receive the double signal necessary to become activated.

HYPERSENSITIVITY IN THE IMMUNE SYSTEM The immune system can be overactive in many situations. These involve mainly allergies and the generation of an immune response to things in the environment that are not commonly pathogenic. There are four main types of hypersensitivity responses, which are the following: •

Type I Hypersensitivity Reaction—this is also referred to as immediate hypersensitivity. In this reaction, the allergen is an antigen that has an IgE antibody associated with it. The IgE antibody binds to the mast cell surface and causes degranulation, releasing histamine and other immune mediators. This leads to a classical allergic response. It happens quickly, which is why it is called an immediate hypersensitivity reaction. It is tested for using allergy skin testing. A serious type I reaction is called an anaphylactic reaction.

•

Type II Hypersensitivity Reaction—this is mediated by IgG and results in the complement-mediated cell killing of mismatched cells (nonself-cells). This is the type of reaction that occurs with blood transfusions that do not match or when the Rh-negative mother makes antibodies against a Rh-positive fetus (called erythroblastosis fetalis).

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•

Type III Hypersensitivity Reaction—this is the type of reaction seen in immune diseases like systemic lupus erythematosus. It is when free, soluble DNA antigens cause antibodies to be made to the DNA, which precipitates in the blood vessel lining. The immune complexes can become lodged in various organs of the body, resulting in inflammation that is chronic in nature.

•

Type IV Hypersensitivity Reaction—this is a delayed hypersensitivity reaction. The individual gets sensitized to an antigen and later, after re-exposure, there is a cellular response or reaction to the antigen. It involves sensitized Th1 cells and the activation of Tc (cytotoxic) T cells. It is delayed because it takes 24-72 hours for the reaction to take place. This is the kind of reaction seen in certain contact sensitivity reactions, poison ivy reactions, and tuberculosis reactions.

AUTOIMMUNE DISEASES Autoimmune diseases involve a reaction to an antigen that belongs to the self. This is when the normal tolerance process breaks down and there is an attack on the body itself. The trigger is unknown but, when it starts, there is the continual production of antibodies against the selfantigen. There are over 100 known autoimmune diseases affecting different parts of the body. The tendency toward getting these types of diseases is genetic. Autoimmune diseases commonly seen in humans include celiac disease (gluten intolerance), type I diabetes (against the beta cells of the pancreas), Graves disease (causing high thyroid conditions), Hashimoto’s thyroiditis (causing a low thyroid condition), systemic lupus erythematosus (against cellular DNA), myasthenia gravis (against the acetylcholine receptor in the neuromuscular junction), and rheumatoid arthritis (causing joint inflammation and damage).

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KEY TAKEAWAYS •

The lymph system takes extracellular fluid and drains it back into the venous blood supply.

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The immune system includes barrier mechanisms, the innate immune system, and the adaptive immune system.

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The innate immune system mainly involves nonspecific phagocytosis of pathogens.

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The primary lymphoid organs are the bone marrow and the thymus.

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The adaptive immune system is specific to certain antigens made by damaged cells and pathogens.

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Cells of the adaptive immune system include B cells, memory cells, T helper cells, T regulator cells, and cytotoxic T cells.

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QUIZ 1. How much lymph fluid gets processed by the lymphatic system per day? a. 500 ml b. 3 liters c. 17 liters d. 20 liters Answer: b. About 20 liters of fluid gets into the tissues from capillary leakage; however, all but three liters are directly reabsorbed by blood vessels. Three liters will be processed by the lymphatic system each day. 2.

What is not a place where the lymph nodes are located? a. Chest b. Axillae c. Groin d. Knee Answer: d. Lymph nodes are found mainly in the chest, abdomen, groin, axillae, and neck region but are not usually found in the area of the knee.

In the lymphatic system, where is the cisterna chyli located? a. Groin b. Upper abdomen c. Neck d. Face Answer: b. The cisterna chyli is located in the upper abdomen and is the start of the thoracic duct.

In general, where does the thoracic duct empty lymph fluid back into the circulation? a. Superior vena cava b. Right atrium 270

c. Inferior vena cava d. Left subclavian vein Answer: d. The left subclavian vein is where the thoracic duct most often empties into, although it is possible to empty in other nearby veins. 5.

Which type of lymphocyte acts in the innate versus the adaptive immune system? a. B lymphocyte b. T lymphocyte c. NK cell d. Plasma cell Answer: c. The NK cell or natural killer cell is a part of the innate immune system and kills both virally-infected cells and certain cancer cells.

What type of cell is least likely to be found inside the thymus gland? a. Macrophages b. Dendritic cells c. Thymocytes d. NK cells Answer: d. The thymus gland contains macrophages and dendritic cells, which phagocytize the thymocytes that do not get selected to become mature T cells. NK cells are not usually seen in the thymus gland.

The tonsils are considered secondary lymphoid nodules. What do they lack that is seen in other secondary lymphoid tissue? a. T cells b. Macrophages c. Capsules d. B cells

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Answer: c. The most obvious difference between tonsils and other lymphoid tissue is that tonsils do not have a capsule. They have other aspects of lymphoid tissue, however. 8.

How does the stomach act as a barrier to pathogens? a. Peyer’s patches beneath the mucosa b. Low pH environment c. Cilia that push pathogens out of the GI tract d. Keratinization of the mucosal surfaces Answer: b. The low pH environment of the stomach acts to kill many pathogens so they cannot enter the rest of the GI tract or get into the body.

9. Which soluble factor in the immune system isn’t a signaling molecule of some sort? a. C-reactive protein b. Chemokines c. Interferons d. Patterned recognition receptor Answer: d. Each of these is a soluble signaling molecule except for a patterned recognition receptor. The PRR is attached to a phagocytic cell and is not a soluble signaling molecule. 10.

Which type of immune cell is not considered a professional antigen presenting cell? a. T helper cell b. Macrophage c. Dendritic cell d. B lymphocyte Answer: a. T helper cells are not professional APCs; the only cells of this type are macrophages, dendritic cells, and B lymphocytes.

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CHAPTER TWELVE: RESPIRATORY SYSTEM The respiratory system is broadly divided into the upper and the lower respiratory tract. The upper respiratory tract is composed of the nose, sinuses, pharynx, larynx and trachea. The lower respiratory tract is primarily made up of the lungs and the bronchial tree. The anatomy and physiology of the gas exchanging structures of the lungs (the alveoli) is also discussed in this chapter.

RESPIRATORY SYSTEM ANATOMY The purpose of the respiratory system is to provide oxygen to all the tissues of the body that engage in cellular respiration, to remove carbon dioxide as a respiratory waste product, and to aid in the acid-base management process. There are also non-vital functions of the respiratory system. For instance, the nose is used to detect odors, speech requires the respiratory system, and the diaphragm is used for the Valsalva maneuver. There are two major zones in the respiratory tract: the conducting zone (which is that part not involved in gas exchange) and the respiratory zone (involved in gas exchange). Most of the structures are found in the conducting zone and do not directly participate in the exchange of oxygen and carbon dioxide. The conducting zone provides a route for air passage, removes debris and pathogens, and begins to warm and humidify the air coming in to the body.

THE NOSE While air can be inhaled through the mouth, the nose is considered the entrance to the respiratory system. There are two parts to the nose, the external aspect and the internal aspect, also referred to as the nasal cavity. The external nose extends from the facial skeleton and has several obvious structures. The root of the nose is that part which begins between the eyebrows. Extending from that is the bridge of the nose, which connects the nose to the root. The length of the nose is referred to as the “dorsum nasi.” The tip of the nose is referred to as the apex. The alae are the cartilaginous

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structures on the side of the nose. The nares are the openings of the nostril and the philtrum is the dip in the upper lip between the mouth and the nose. The bridge and the root of the nose are structured out of bone, while the rest is cartilage. The septal cartilage is the midline cartilage that forms the dorsum nasi and the alar cartilage surrounds the nares, forming the lateral margin of the nose. The nasal septum is the interior part of the nose, made of cartilage. Inside of the nose, part of the nasal septum is made from a plate composed of the ethmoid and vomer bones. The lateral wall of the nasal cavity has three bony projections, referred to as the superior, middle, and inferior conchae. The inferior conchae are made from separate bones, while the superior and middle conchae are part of the ethmoid bone. The conchae disrupt the airflow and help increase the “warming” surface area of the nose. The bottom of the nasal cavity is the hard palate in the front and the soft palate in the back. This part is made from muscle tissue. There are internal nares that acts as the exit point of the nose, causing air to travel to the pharynx. The conchae act to increase the surface area of the tissues of the nasal cavity, which helps to warm and purify the air as it passes through the nose. They also conserve water and prevent the dehydration of the epithelium of the nose by causing water to be trapped in the exhalation process. The paranasal sinuses are an important part of the nasal structure. These are located in bones and contain air-spaces that will also warm and humidify the air. There are four paranasal sinuses: the frontal sinus, the sphenoidal sinus, the ethmoidal sinus, and the maxillary sinus. They will lighten the weight of the skull and produce mucus to overly the epithelium. Figure 95 shows the anatomy of the sinuses and the pharynx:

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The anterior portion of the nasal cavity and the nares are lined with mucous membranes that contain hair follicles and sebaceous glands that prevent the passage of debris into the nasal cavity. The olfactory epithelium is found at the roof of the nose to aid in the sense of smell. The paranasal sinuses, the meatuses, and the conchae are lined with respiratory epithelium, which is pseudostratified columnar epithelium. It is ciliated epithelium that can bring bacteria out of the respiratory tract. There are goblet cells that produce mucus, which also traps debris that is breathed in. Cold air will slow the movement of cilia so that mucus accumulates. This is why people have a runny nose when exposed to the cold. The goal is to keep the air as warmed and as humidified as possible. There are capillaries that dilate in the nasal mucosa in order to warm the air further in cold weather. There are also cells in the nasal mucosa that produce lysozyme—a common enzyme that kills bacteria by damaging their cell walls. Cells of the immune system will reside beneath the respiratory epithelium in order to provide protection against pathogens.

PHARYNX The pharynx is a muscular tube that receives the air from both the nose and mouth. There are three parts that are arbitrarily defined as the nasopharynx, oropharynx, and laryngopharynx. Of these, only the nasopharynx is strictly associated with the respiratory tract. 275

The nasopharynx contains the three conchae of the nasal cavity. The top of this structure includes the adenoids or “pharyngeal tonsils” This is a lymphoid nodule like the tonsils we have already talked about and contain lymphocytes that have the capacity to destroy pathogens that come in through the nose. These, like the oropharyngeal tonsils, are larger in children and smaller in adults, sometimes disappearing completely in adults. Other structures of the nasopharynx are the uvula (a teardrop-shaped structure hanging from the soft palate) and the soft palate. These structures will move upward during swallowing in order to keep food from entering the nasal cavity during the act of swallowing. There is also the Eustachian tube, which connects the nasopharynx to the middle ear cavity. The oropharynx is used for both air and food passage. The front of it is the boundary of the oral cavity and is referred to as the “fauces,” while the upper border is the nasopharynx. The epithelium anteriorly changes from ciliated pseudostratified columnar epithelium to stratified squamous epithelium. There are two separate sets of tonsils in this area: the palatine tonsils (on either side of the fauces) and the lingual tonsils, located at the base of the tongue. The laryngopharynx is the lowermost aspect of the pharynx and is located behind the larynx. It is used for digestion and respiration. The anterior part (front part) of the laryngopharynx opens into the larynx. The posterior part (back part) opens into the esophagus.

LARYNX The larynx is made from cartilage. It connects the pharynx to the trachea, sending in just the right amount of air per breath. There are several separate cartilaginous structures that make up the larynx. The thyroid cartilage is located in the front (anteriorly); the epiglottis is above the vocal cords, and the cricoid cartilage is below the cords. The thyroid cartilage is the “Adam’s apple” and is more prominent in men. It is the largest cartilage of the larynx. There are three smaller cartilages that are paired. These are the cuneiforms, the corniculates, and the arytenoid cartilages. Figure 96 shows what the structures of the larynx look like:

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The epiglottis is the piece of cartilage that covers the trachea during swallowing. The glottis is made of the true vocal cords, which are white, membranous folds that are attached to the thyroid and arytenoid cartilages. The vestibular folds are the false vocal cords, which are folded segments of mucous membrane. The true cords will oscillate and separate in order to produce noise of different pitches. The upper part of the larynx is continuous with the laryngopharynx and thus is lined with stratified squamous epithelium. It gradually develops respiratory epithelium, which is ciliated and contains goblet cells that produce mucus that traps the debris and potential pathogens as they enter the trachea. In this case, the cilia beat in one direction in order to push mucus upward toward the laryngopharynx, where it can be coughed out or swallowed.

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TRACHEA The trachea is referred to as the windpipe. It starts in the larynx and ends at the lungs. It is composed of pieces of hyaline cartilage, each of which is C-shaped and number up to twenty in total. The back wall of the trachea consists of a fibroelastic membrane made from elastic connective tissue and the trachealis muscle. This membrane stretches to allow the trachea to expand during the inhalation and exhalation process. It can also contract during forced exhalation. The trachea is lined with respiratory epithelium, which is ciliated pseudostratified epithelium.

BRONCHIAL TREE The bronchial tree starts at the trachea where it branches off to form the left and right mainstem bronchi. This is also called the carina. They are lined with typical respiratory epithelium and mucus-producing goblet cells. The carina is a specialized structure consisting of nerve tissue that causes violent coughing if there is a foreign body present. There are rings of cartilage just as is seen in the trachea that prevent collapse of the bronchial tree. These mainstem bronchi enter the lungs at the hilum, which is a place where all of the major nerve and vessel structures enter the lungs as well. The bronchial tree is the collection of branches that get smaller and smaller, continuing as part of the conducting zone, in order to spread the air out to all parts of the lung. There is a mucous membrane that traps debris and possible pathogenic organisms. A bronchiole is the terminal end of the bronchial tree. These are about one millimeter in diameter wit about 1000 total terminal bronchioles per lung. These have muscular walls that can contract and relax in order to increase or decrease the airflow in the lungs but they do not require cartilage to remain open as is in the case with bronchi. The ends of the terminal bronchioles are referred to as respiratory bronchioles. These are part of the respiratory zone and not the conducting zone. They open out into clusters of alveoli.

ALVEOLI Alveoli are clusters of sacs that are connected to the rest of the lungs via alveolar ducts. These are where gas exchange occurs. One alveolus is only about 200 micrometers in diameter. The 278

walls are elastic in order to stretch during the time air enters them. Each alveolus is connected to another by alveolar pores, which maintain the air pressure between the alveoli. Figure 97 illustrates the anatomy of the alveolus:

The wall of the alveolus consists of three different cell types. These include the following: 1) type I alveolar cells, 2) type II alveolar cells, and 3) alveolar macrophages. Type I alveolar cells are squamous epithelial cells, making up 97 percent of the surface area of the alveoli. These are very permeable to gases. Type II alveolar cells secrete pulmonary surfactant, which is a proteinaceous and phospholipid-containing substance that decreases the surface tension of the alveolus. The alveolar macrophage is actually an immune system cell that performs phagocytic functions. These are actually dendritic cells that eliminate anything that has reached the alveolus in the breathing process. The type of epithelium found in the alveolus is the simple squamous type that has a very thin basement membrane. It needs to be so thin so it can pick up oxygen and give off carbon dioxide. It borders the endothelial membrane of the capillaries—the combination of which 279

makes the respiratory membrane that is only about 0.5 millimeters thick. It is through this membrane that gas exchange occurs.

LUNG ANATOMY The lung contains aspects of both the respiratory and conducting zones. Its main function is to participate in the exchange of oxygen for carbon dioxide in the process of pulmonary respiration. The gas exchange area is large—about 70 square meters in area. This is necessary for the most efficient exchange of gases with each breath. The lungs themselves are paired and connected to the trachea by the right and left mainstem bronchi. The lower border of the lungs is the diaphragm—a muscular structure involved in the action of “breathing in.” The lungs are completely enclosed by a pleural lining. The right lung is larger but shorter than the left lung. The left lung is smaller to make room in the left chest for the heart. The lungs consist of lobes separated by large fissures. There are three lobes to the right lung and two lobes to the left lung. Each lobe is divided into multiple bronchopulmonary segments. Each segment gets air from its own tertiary bronchus and each has its own artery. A pulmonary lobule is a subdivision of a segment. It is formed when the bronchi turn into bronchioles. There is an interlobular septum consisting of connective tissue that separates the lobules from one another. The lungs need to be highly vascularized to be available for gas exchange. There are two types of vessels in the lungs: those that participate in the gas exchange and those that supply oxygenated blood to the lung tissue. The pulmonary circulation starts with the pulmonary artery leading out of the right ventricle. It carries deoxygenated blood to smaller and smaller vessels until a single arteriole and a single venule drain a single pulmonary lobule. They ultimately form a pulmonary capillary network that surrounds the different alveoli. Together, the capillary wall and the alveolar wall form the respiratory membrane. The oxygenated blood leaves the veins via the hilum.

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The parasympathetic and sympathetic nervous system both innervate the lungs. These control the dilation and constriction of the airways. The parasympathetic nervous system results in bronchoconstriction, while the sympathetic nervous system causes bronchodilation. The autonomic nervous system also helps regulate the cough reflex and the regulation of the oxygen and carbon dioxide levels in the lungs. The lining of the lungs is called the pleura. There is a right and left pleural lining that cover the lungs as the visceral pleura. This is the layer that is closest to the lungs and lines the fissures of the lobes of the lungs. The parietal pleura is a reflection of the visceral pleura and lines the inner aspect of the thoracic wall. The space between these two linings is called the pleural cavity. The pleurae form two major functions. First, they produce pleural fluid, which is secreted by mesothelial cells (on both layers) and lubricates the space between the two layers. This reduces friction between the two layers. It also creates “surface tension” that keeps the two layers in contact with one another. The pleurae also prevent the spread of infection by separating the different organs in the chest cavity.

PULMONARY VENTILATION Pulmonary ventilation is also referred to as the “act of breathing” or the movement of air into and out of the lungs. There are three pressures involved in the act of breathing: the atmospheric pressure, the alveolar pressure, and the intrapleural pressure (the pressure inside the pleural cavity). The act of breathing depends on the relationship between these pressures. Atmospheric pressure is the amount of force exerted by gases in the air around the body. This is expressed in millimeters of mercury. Air pressure is about 760 mm Hg, which is also called “one atmosphere.” This is actually the air pressure that exists in the environment at sea level. When it comes to pulmonary ventilation, a pressure is said to be “negative” if it is less than atmospheric pressure and “positive” if it is greater than atmospheric pressure. This means that at one atmosphere or the air pressure outside, the pressure is considered to be “zero.” The intra-alveolar pressure is the pressure of air within the alveoli, which changes during the different phases of breathing. This pressure eventually equalizes with the atmospheric pressure 281

but, in reality, it changes with the breathing effort. The intrapleural pressure is the pressure within the pleural cavity—between the visceral and the parietal pleurae. This pressure also changes during the breathing effort. The intrapleural pressure is always lower than (or more negative than) the intra-alveolar pressure. While it fluctuates, the mean intrapleural pressure is -4 mm Hg throughout the cycle of breathing. This is what keeps the lungs and the thoracic wall together. The transpulmonary pressure is the difference between the intrapleural pressure and the intraalveolar pressures, which determines the lung size. The higher the transpulmonary pressure, the greater the size of the lungs. Breathing is dependent upon the contraction and relaxation of the muscle fibers of the thoracic wall and the diaphragm. Lungs are passive transporters of oxygen and do not actually participate in the breathing process. They only participate in breathing by being adherent to the chest wall. The main action of breathing is caused by the diaphragm, which contracts to cause a pressure change inside the chest cavity. The intercostal muscles participate to a lesser degree. The size of the alveoli determines how big and how much the lungs can expand. At some point, the airway resistance is overcome and the air rushes into the alveoli. The resistance increases with the smaller size of the bronchioles. The surfactant keeps the surface tension of the alveoli low enough so that the they do not collapse in the act of expiration. The chest wall, in addition, must be compliant enough to allow the chest to expand during inhalation. It is natural for air to flow down a pressure gradient from an area of high pressure to an area of low pressure. It is the differences in the atmospheric pressure and the intra-alveolar pressure that draws air into the lungs. When the pressure is greater in the alveoli, there is a natural exit of air from the lungs. A respiratory cycle is one inspiration (breathing in) and one expiration (breathing out). The contraction of the diaphragm causes a relative negative pressure in the alveoli, so air rushes in to make full inspiration; upon relaxation of the diaphragm, the pressure equalizes again as the air flows out of the lungs. One can force air out of the lungs actively although this is not the

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normal state of quiet breathing (called eupnea). This doesn’t require thought and is the type of breathing that occurs at rest. It is also possible to have shallow breathing that only involves the intercostal muscles. Forced breathing or hyperpnea is a type of breathing that occurs during exercise or singing. During forced breathing, both inspiration and expiration involves muscle contraction. The muscles of the neck (such as the scalene muscles) causes further lifting of the chest and deeper breathing. Accessory muscles of the abdomen (such as the oblique muscles) will contract and force the lungs to expire more than normal, forcing air out to a greater degree than what is seen in quiet breathing.

RESPIRATORY VOLUMES There are several measured respiratory volumes used to define breathing and to help in identifying breathing disorders. There are four major volumes and several respiratory capacities you should know about, including: •

Tidal volume (TV)—this is the amount of air entering the lungs during quiet breathing.

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Expiratory reserve volume (ERV)—this is the amount of air that can be forcefully breathed out.

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Inspiratory reserve volume (IRV)—this is the amount produced by deep inhalation.

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Residual volume (RV)—this is the air left in the lungs after forced expiration (it keeps the alveoli from relaxing).

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Total lung capacity (TLC)—this is the sum of all of the lung volumes just listed (TV, ERV, IRV, RV). It is the amount of air held in the lungs after a full inhalation (about 6000 milliliters in men and 4200 milliliters in women).

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Vital capacity (VC)—this is the sum of all volumes except the residual volume (about 4000 milliliters in females and 5000 milliliters in men).

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Inspiratory capacity (IC)—is the maximum amount of air that can be inhaled past the normal tidal expiration (the tidal volume plus the inspiratory reserve volume).

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Functional residual capacity (FRC)—the amount of air that remains in the lungs after a normal expiration or the sum of the expiratory reserve volume and the residual volume.

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Anatomical dead space—this is the amount of air in the airways that never reaches the alveoli.

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Alveolar dead space—this is the air found in the alveoli that, because of disease, doesn’t get involved in gas exchange.

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Total dead space—the anatomical dead space plus the alveolar dead space (all the air that doesn’t participate in gas exchange).

CONTROL OF VENTILATION Breathing is largely subconscious although it is possible to consciously breathe. The respiratory rate is defined as the number of breaths per minute. The main respiratory center is located in the medulla of the brain. It is responsive to the CO2 level, O2 level, and pH level in the bloodstream. The total respiratory rate is higher in children than in adults so that, as an adult, the normal breath rate is 12-18 breaths per minute. The medullary respiratory center sets the breathing rhythm; the VRG or ventral respiratory group integrates the important information coming into the medulla; the DRG or dorsal respiratory group integrates the data from the chemoreceptors and stretch receptors in the periphery of the body; the PRG or pontine respiratory group will modify the function of the respiratory centers in the medulla. Both the aortic and carotid body in these vessels will monitor the pH, O2 level, and CO2 level. The hypothalamus will keep track of the body temperature and emotional state to influence the respiratory rate; the cortex has control over voluntary breathing efforts. There are proprioceptors that send impulses to the brain about joint and muscle movements; pulmonary irritant reflexes protect the lungs from foreign body aspiration. The inflation reflex prevents the lungs from becoming over-inflated. The pons and medulla have respiratory centers. In the medulla oblongata, there are the dorsal respiratory group (DRG) and the ventral respiratory group (VRG). The DRG helps maintain the

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continual rate of breathing by causing diaphragmatic breathing. The VRG is involved in forceful breathing by stimulating the accessory muscles in forced inspiration and expiration to contract. In the pons, there is a second respiratory center, the pontine respiratory group. This has both an apneustic center (to stimulate the depth of breathing in deep breathing) and the pneumotaxic center (that allows relaxation after inspiration, controlling the respiratory rate). Each of these brain centers responds to systemic stimuli in a feedback loop. Increased stimulation from the periphery causes forced breathing. It is the CO2 level that primarily controls respiration (not the O2 level). There are both central chemoreceptors and peripheral receptors (in the carotid arteries and aortic arch) that measure the concentration of hydrogen ions, CO2, and O2. Increased CO2 (and hydrogen ions) in the brain will cause the central chemoreceptors to trigger contraction of the intercostals and the diaphragm, increasing the rate and depth of respiration. This cause homeostasis and normalization of the CO2 and Hydrogen ion concentrations. Low CO2 levels decrease the rate and depth of respirations. Increased CO2 means increased hydrogen ions. The same is true of increased exercise that leads to lactic acid buildup. When the blood is more acidic, the ventilatory rate and depth will increase to remove CO2, normalizing the blood pH. If the O2 level is low (at 60 mm Hg or less), the peripheral chemoreceptors will increase the breathing rate. It takes a significant drop in O2 levels to cause this change in breathing. Increased body temperature will increase the respiratory rate. The hypothalamus and limbic system make one excited or trigger the fight-or-flight response, which will increase the respiratory rate as well. Pain and emotions will increase the breathing rate.

GAS EXCHANGE Gas exchange is the major function of the lungs; this happens at the respiratory membrane, which is the fusion of the alveolar wall and the capillary wall. The atmosphere we breathe in consists of mainly oxygen, carbon dioxide, and nitrogen—each of which has a partial pressure that adds up to a total air pressure. The partial pressure is the pressure of one type of gas in a gaseous mixture. In order of decreasing partial pressures, there is nitrogen (78 percent of air), oxygen (21 percent of air), water (0.4 percent of air), and carbon dioxide (0.004 percent of air). 285

In the lungs, the gas in the air must go into the liquid blood. According to Henry’s Law, the higher the partial pressure of a gas, the greater number of gas particles that will dissolve in liquid. The solubility of the gas in a liquid also plays a role. Nitrogen is high in the air but low in blood because it doesn’t dissolve very well. The composition of atmospheric air is different than alveolar gas. There is more water vapor in alveolar gas because of the humidification process. There is also more carbon dioxide in alveolar air and less oxygen (because of exchange of gases). The end result, however, is that oxygen will enter the bloodstream and carbon dioxide will leave the bloodstream.

VENTILATION AND PERFUSION Ventilation is the movement of air in and out of the lung, while perfusion is the flow of blood in the lung’s capillaries. The ventilation must match perfusion in order to have efficient gas exchange. Imbalances do occur naturally, however, if alveolar ducts are blocked and because of the effects of gravity on the blood flow. Disease can cause a ventilation/perfusion (or V/Q) mismatch. The partial pressure of oxygen in the alveoli is about 104 mm Hg, whereas the same value in the oxygenated venous blood in the lungs is about 100 mm Hg, indicating a reasonable efficiency of gas exchange. If it becomes less efficient, the difference between these two pressures is greater. If ventilation is not enough in an alveolus, there is redirection of blood flow to “better” more oxygenated alveoli. There can be increased dilation of vessels in the lungs as well, increasing the rate of gas exchange. The pH, oxygen level, and CO2 level will affect the blood flow in the capillaries. The diameter of the airways determines ventilation, while the diameter of the blood vessels determines perfusion. The greater the CO2 concentration in the bronchioles, the greater is the bronchiolar dilation. The same is true of a low oxygen level in the bloodstream. The goal then is to allow more CO2 to be exhaled from the body. The more oxygen in the alveoli, the more the pulmonary vessels dilate to increase the blood flow and oxygen exchange. There are two places where gas exchange occurs: 1) at the respiratory membrane in the alveoli, and 2) in tissues, where CO2 enters the bloodstream and O2 enters the cells. The lung gas

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exchange process is called external respiration and the tissue gas exchange is referred to as internal respiration. All of this happens through simple diffusion, there are no energy requirements or transporters involved. The gases simply follow a pressure gradient. Deoxygenated blood from the pulmonary artery goes into an alveolar capillary network that helps to create the respiratory membrane. This is where the gas exchange occurs. A small amount of oxygen is dissolved in blood but more is bound to hemoglobin in the RBCs. This oxygenated blood reenters the heart via the pulmonary vein. Carbon dioxide is mostly dissolved in the blood but some is in hemoglobin. The partial pressure of oxygen in the alveoli is 104 mm Hg, while the partial pressure of oxygen in the capillary is just 64 mm Hg. This leaves a huge pressure gradient that allows for the rapid diffusion of oxygen across the respiratory membrane. The same is true in the case of carbon dioxide. The partial pressure of the CO2 in the capillary is 45 mm Hg, while the same value in the alveoli is 40 mm Hg. This leaves just a 5 mm Hg pressure gradient. This is enough, however, that there is exchange of gas across the membrane. Internal respiration is gas exchange at the tissue level. The partial pressure of oxygen in tissues is about 40 mm Hg because it is used as part of the cellular respiration process. In contrast, the partial pressure of O2 in the tissue capillaries is 100 mm Hg. This creates a dissociation of O2 from hemoglobin and accounts for a 60 mm Hg pressure gradient. The blood that isn’t very oxygenated is burgundy or dull red in color. Its partial pressure is about 40 mm Hg and the partial pressure CO2 in deoxygenated blood is 45 mm Hg.

OXYGEN TRANSPORT Oxygen isn’t very soluble in blood so only about 1.5 percent of the total amount is actually dissolved in the bloodstream. The rest, 98.5 percent, is bound to hemoglobin, which contains heme that binds oxygen. Because there are four heme molecules per molecule of hemoglobin so up to four molecules of oxygen will bind to one hemoglobin molecule. Figure 98 illustrates what a hemoglobin molecule looks like:

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Oxyhemoglobin is the bright red molecule that has oxygen bound to it. As you can see by the image, hemoglobin is a quaternary structure with four subunits. The binding of the first oxygen molecule causes a conformational change in hemoglobin that makes it more readily able to bind additional oxygen molecules. The opposite change from oxyhemoglobin to deoxygenated hemoglobin is also made easier after the first oxygen molecule drops off. Saturated hemoglobin has all of the oxygen molecules attached to it. It gradually goes from oxygenated hemoglobin to deoxygenated hemoglobin in the tissues. Tissues that are highly metabolic will use up more oxygen so the partial pressure of oxygen is even lower—as low as 20 mm Hg. This leads to a high differential in the partial pressures between the vessels and the tissues. This is often the case in muscle tissue. Fatty tissue has a lower metabolic rate. It therefore has a lesser gradient and a decreased number of oxygen molecules diffuse across the tissue cell membranes. This incidentally leads to an oxygen reserve in the blood that can be used if there is increased oxygen demand. There are factors that influence the dissociation of oxygen from hemoglobin. Higher temperatures will encourage dissociation so, in highly active tissues, there is more heat given

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off and there is a higher dissociation of oxygen into the tissues. The hormones epinephrine, androgens, growth hormone, and thyroid hormones will increase the dissociation of oxygen from hemoglobin. These will do this by stimulating glycolysis in the RBCs, which causes a byproduct that encourages the dissociation process. More acidic tissues will have greater oxygen dissociation.

CARBON DIOXIDE TRANSPORT Carbon dioxide is transported three ways in the bloodstream. Some is dissolved directly in the blood; some is transported via hemoglobin; and some is transported as bicarbonate ions dissolved in blood plasma. About 7-10 percent of CO2 is directly dissolved as a gaseous substance. About 70 percent goes into the bicarbonate buffer system as bicarbonate ions. It helps to regulate the acid-base balance in the bloodstream. There is a high concentration of bicarbonate in erythrocytes particularly. It exchanges with chloride (another negative ion) in order to stay in the RBCs. About 20 percent of CO2 is bound by hemoglobin that is transported to the lungs. It isn’t bound in similar ways as oxygen; instead, it is bound to different amino acids on the hemoglobin molecule to make carbaminohemoglobin. It is blue to purple in color, which helps contribute to the color of deoxygenated blood. Because oxygen has a greater affinity for hemoglobin than CO2, the hemoglobin must be relatively free of oxygen before CO2 will have the ability to bind.

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KEY TAKEAWAYS •

The respiratory tract is divided into a conducting and a respiratory zone.

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The inlet for the respiratory tract is the nose, which traps debris and helps humidify the air.

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The respiratory epithelium contains cilia and mucus-containing goblet cells that trap and move bacteria and debris that is breathed in.

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The alveolus is where oxygen and carbon dioxide gas exchange occurs.

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Gas exchange in the tissues and lungs will happen because of simple diffusion of the gases, O2 and CO2.

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QUIZ 1. In anatomical terms, what is the tip of the nose called? a. Root b. Bridge c. Dorsum nasi d. Apex Answer: d. The tip of the nose is called the apex. The root of the nose is between the eyebrows; the bridge is the part that connects the rest of the nose; the dorsum nasi is the length of the nose. 2.

What part of the nasal cavity serves to increase the surface area of the inside of the nose? a. Nares b. Palate c. Conchae d. Septum Answer: c. The nasal conchae have several purposes, the most obvious of which is to increase the surface area of the nasal cavity so the air can be warmed and moisturized to a greater degree.

The respiratory epithelium contains cilia and is what type of epithelium? a. Stratified squamous epithelium b. Simple columnar epithelium c. Pseudostratified columnar epithelium d. Simple cuboidal epithelium Answer: c. This epithelium is relatively unique to the respiratory tract and is ciliated pseudostratified columnar epithelium.

What are the lymphoid structures at the base of the tongue called?

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a. Lingual tonsils b. Adenoids c. Pharyngeal tonsils d. Palatine tonsils Answer: a. The lingual tonsils are located at the base of the tongue. The adenoids and pharyngeal tonsils (located in the nasopharynx) are the same thing. The palatine tonsils are on the lateral side of the oropharynx—at the fauces. 5.

Which cell type is found in the greatest abundance in the respiratory alveoli? a. Type I alveolar cell b. Type II alveolar cell c. Dendritic cell d. Alveolar macrophage Answer: a. The most common cell type by far is the type I alveolar cell, making up 97 percent of the cells in the alveolus.

Which type of epithelium lines the alveoli? a. Simple cuboidal epithelium b. Pseudostratified columnar epithelium c. Simple squamous epithelium d. Stratified squamous epithelium Answer: c. The epithelium that lines the alveoli is simple squamous epithelium.

What is an effect of the parasympathetic nervous system on the lungs? a. It increases the respiratory rate and depth. b. It causes bronchoconstriction. c. It causes bronchodilation. d. It causes increased depth but decreased rate of respirations.

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Answer: b. The parasympathetic nervous system causes bronchoconstriction of the bronchial tree. 8.

What is the major force behind pulmonary ventilation or breathing? a. Relaxation of the intercostal muscles b. Contraction of the intercostal muscles c. Contraction of the diaphragm d. Relaxation of the diaphragm Answer: c. It’s the contraction of the diaphragm that participates the most in the act of breathing. The act of inspiring is active, while the act of expiring is passive.

What is the main thing the central chemoreceptors in the brain respond to in order to affect the rate and depth of breathing? a. CO2 level b. Hydrogen ion level c. O2 level d. Lactic acid level Answer: a. It is the CO2 level which will most commonly affect the chemoreceptors in the brain in order to affect the rate and depth of breathing.

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Which gas has a partial pressure in the air (atmosphere) that is the highest? a. Oxygen b. Nitrogen c. Water d. Carbon dioxide Answer: b. Nitrogen has the highest partial pressure making up more than 78 percent of the total composition of the air in the atmosphere.

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CHAPTER THIRTEEN: DIGESTIVE SYSTEM The digestive system includes everything involved with the digestive process ranging from the mouth to the anus. This also includes other structures involved in digestion, including the liver, gallbladder, and the exocrine portion of the pancreas. The different anatomical structures included as part of the digestive system are also covered, including how they take food and turn it into nutrients used by the entire body.

STRUCTURE AND BASIC FUNCTION OF THE DIGESTIVE SYSTEM The basic function of the digestive system is to take in food, mechanically and chemically break the food into its constituents, and absorb the breakdown products into the system. While the bulk of absorption takes place in the small intestine, the entire digestive tract (and other systems) plays a role in the digestive process. The following is a quick breakdown of how the body engages in digestions: •

The cardiovascular system will provide blood for the absorption of nutrients.

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The endocrine system will send hormones that regulate the different organs of the digestive system.

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The skin synthesizes vitamin D which is important in calcium absorption in the GI tract.

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The lymphoid and immune systems will participate in pathogen defense and in the absorption of lipids (as is done by the lacteals in the digestive tract).

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The nervous system has sensory and motor nerves that help smooth muscle contract in the GI tract.

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The kidneys manufacture the active form of vitamin D that allows for increased calcium absorption.

The digestive system is divided into the alimentary tract or alimentary canal as well as the accessory digestive organs, which are essential for the function of the digestive system. The

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alimentary canal is the GI tract—a single tube that is 25 feet in length, starting in the mouth and ending in the anus. In between are the pharynx, esophagus, stomach, small intestine, and large intestine. The accessory digestive organ system will aid in the breakdown of nutrients. It includes the teeth and tongue, which mechanically break down food, and the salivary glands, which chemically break down food. The pancreas will secrete enzymes to assist in digestion as will the liver. The gallbladder stores bile necessary for lipid digestion.

ALIMENTARY CANAL HISTOLOGY While the histology of the alimentary canal will differ slightly depending on the specific organ, there are many similarities throughout the tract. There are four basic layers to the wall of the GI tract, from the inner layer to the outer layer: the mucosa, the submucosa, the muscularis, and the serosa, which is the same as the mesentery. The mucosa or mucous membrane is the innermost layer. The epithelium is slightly different depending on the location in the digestive tract. The mouth, pharynx, esophagus, and anus has stratified squamous epithelium that is non-keratinized. In the stomach and intestines, however, this epithelium is simple columnar epithelial tissue. Among the epithelial cells are mucus-secreting goblet cells as well as enteroendocrine cells that secrete locally-acting hormones. There is rapid renewal of these cells because of wear and tear on the system. There is a lamina propria that contains lymphatic and blood vessels responsible for transporting nutrients through the alimentary canal. There is MALT tissue in this area, which is mucosaassociated lymphoid tissue. These are where the Peyer’s patches are located as well. Also, in the mucosa, is the muscularis mucosa (not the muscularis layer) that has smooth muscle, which forms the folds in the mucosa for increasing the absorptive surface of portions of the GI tract. The submucosa is an area of dense connective tissue just beneath the mucosa. It has blood and lymphatic vessels as well as submucosal glands, which release digestive secretions, and a nerve plexus called the submucosal nerve plexus.

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The layer outside of the submucosa is called the muscularis layer or muscularis externa. In some places, there is an inner circular layer and an outer longitudinal layer. These promote mechanical digestion and move food through the canal. In other places, there is skeletal muscle, allowing for voluntary control over both swallowing and defecation. In the stomach, there are three layers that allow for mechanical churning. In the colon, there are segregated longitudinal muscles instead of a solid muscle. These are known as the tenia coli. The serosa is the outer layer of the alimentary canal. It is seen in that part of the alimentary canal within the abdominal cavity. It exists as the visceral layer surrounding the tissues and a parietal layer within the abdominal cavity. There is the adventitial layer instead in the mouth, pharynx, and esophagus, which is mainly made of collagen.

NERVOUS SYSTEM IN THE GI TRACT The nervous system plays a role throughout the GI tract. There are receptors in the mouth that are triggered when food enters the mouth. They help detect the taste of food and assist with the chewing and swallowing process. The enteric nervous system is considered “intrinsic” and runs from the esophagus to the anus and is considered somewhat separate from the rest of the nervous system. There are two plexuses as part of the alimentary canal. The myenteric plexus is also referred to as the plexus of Auerbach, which lies in the muscularis layer. It is responsible for motility in the GI tract, controlling the force of contractions of the muscularis layer. The submucosal plexus or plexus of Meissner is in the submucosal layer; it is responsible for the regulation of digestive secretions and the GI tract’s reaction to the presence of food. There are also parasympathetic and sympathetic nerves that supply the GI tract externally or “extrinsically.” The sympathetic nervous innervation will decrease GI secretions and motility, while the parasympathetic nervous innervation will increase the GI secretions and motility so that digestion can take place. These two arms of the sympathetic nervous system interact with the enteric nervous system.

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CIRCULATION IN THE GI TRACT The blood vessels have two functions in the GI tract. They will transport the amino acids and simple carbohydrates after digestion but do not participate in lipid transport, which is part of the lacteal system of the lymphatic system. The arteries come from the aortic arch, the thoracic aorta, and the abdominal aorta. The large celiac trunk will provide circulation to the stomach, duodenum, and liver, while the superior and inferior mesenteric arteries supply both the small and large intestines. Most absorption comes into the veins that ultimately provide nutrients to the liver.

THE PERITONEUM The peritoneum, as mentioned, consists of a visceral and parietal peritoneum. There is a peritoneal space that consists of a small amount of fluid. Like the pleural space, it is more of a “potential space” that usually contains very little except for lubricant to decrease friction. There is really no back wall to the peritoneum, however; instead, it folds around the abdominal organs and affixes them to the back of the abdomen. Behind it is the retroperitoneal space containing the duodenum, pancreas, part of the large intestine, and the kidneys.

PROCESS OF DIGESTION There are six activities associated with the act of digestion. These include the following: •

Ingestion—this involves the intake of food through the mouth. There is partial mechanical and chemical digestion, with enzymes that are able to break down both carbohydrates and lipids through the action of lingual lipase. The surface area of food is increased and the right-sized boluses are made and swallowed.

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Propulsion—this happens largely involuntarily, through the action of propulsive muscles and peristalsis. Peristalsis involves the contraction and relaxation of the smooth muscles of the alimentary canal, which mixes food and sends it on its way through the canal.

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Mechanical digestion—this involves increasing the surface area of the food through chewing and the churning of stomach muscles into chyme. It also happens in the small intestine, when the chyme is churned back and forth in segments in a process called “segmentation.”

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Chemical digestion—this is the enzymatic breakdown of food into its chemical constituents. It starts in the mouth, and continues to take place in the stomach and proximal small intestine.

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Absorption—this is the uptake of the nutrients into the bloodstream through the mucosal epithelial cells, mainly in the small intestine, although a small mount also happens in the stomach.

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Defecation—this is a basic process by which there are undigested materials from the food that is eliminated from the body through the feces.

REGULATION OF DIGESTION The regulation of digestion comes through neural impulses and endocrine mechanisms. There are intrinsic and extrinsic activities that take place. In the nervous system, a variety of receptors are present (osmoreceptors, chemoreceptors, and mechanoreceptors) that regulate the digestive system. These receptors can detect a great deal about the food taken in and can send signals to digestive organs to alter their behavior to enhance the digestive process. There are nerve plexuses in the walls of the alimentary canal that will interact with other aspects of the digestive system. There are long reflexes that involve the brain’s and the autonomic nervous system’s responses to stimuli outside of the digestive tract. There are short reflexes that involve the nerve plexuses in the alimentary canal and that act more locally to coordinate the digestive system. The sight of food can initiate a long reflex with the medulla to send a signal to the stomach to enhance the production of hydrochloric acid and enzymes in preparation for the food intake. The same thing can happen with a short reflex, which involves stomach distension triggering gastric juice secretions.

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There are many hormonal influences on the digestive process. The stomach, for example, produces gastrin in response to food ingestion. This stimulates hydrochloride acid production in the stomach. Secretin is made by the duodenum, which stimulates bicarbonate production by the pancreas. Other hormones include cholecystokinin and gastric inhibitory peptide. These are hormones released into the bloodstream that all have GI effects.

MOUTH ANATOMY AND PHYSIOLOGY The mouth or oral cavity is the entryway to the digestive system. The lips have skin covering them on the outside (but with a thin layer of keratin) and are red because of their increased vascularity. The inner layer is mucus membrane, like the rest of the mouth. The mouth is surround by the orbicularis muscle. Just inside the mouth is the labial frenulum that attaches the inner surface of the upper and lower lip to the gums. The side of the mouth is the buccal side or the cheek side. The mucous membrane is non-keratinized, stratified squamous epithelium. Figure 99 is the illustration of the mouth anatomy:

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The opening of the mouth is called the oral vestibule. The exit of the mouth into the oropharynx is called the fauces. The roof of the mouth is composed of the hard and soft palate. The hard palate is created by the maxillary bones and the palatine bones; it provides a counterforce for the tongue to push on during mastication (chewing). Posterior to that is the soft palate, which is largely muscular and changes in shape during different activities of the mouth. The uvula is a fleshy projection beneath the back edge of the soft palate. It moves upward during swallowing to keep food from entering the nasopharynx. There are two arches along the lateral side of the posterior aspect of the tongue: the palatoglossal arch and the palatopharyngeal arch. Between the two are the palatine tonsils. At the base of the tongue are the lingual tonsils.

TONGUE The tongue assists with ingestion of food, mechanical digestion, food sensation (of temperature, texture, and taste), chemical digestion (through the release of lingual lipase), vocalization, and swallowing. It is attached to the mandible, the styloid processes of the temporal bones, and the hyoid bone. It is located on the floor of the mouth and is actually two embryological structures connected by a medial septum. There are intrinsic and extrinsic muscles in the tongue. The intrinsic muscles are located solely within the tongue. These are the longitudinalis superior, the longitudinalis inferior, the transverse linguae, and the verticalis linguae muscles. They aid in speech and swallowing. Extrinsic muscles supporting the tongue include the hyoglossus, mylohyoid, genioglossus, and styloglossus muscles. They insert outside of the tongue and are involved in positioning food for chewing and swallowing and forming chewed food into a bolus. The upper surface and sides of the tongue have a number of papillae, which are actually extensions of the lamina propria of the tongue mucosa. There are several different types that are named because of their shape: the fungiform papillae are shaped like mushrooms; the filiform papillae are thin and long. The fungiform papillae contain the taste buds, while the

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filiform papillae have the touch receptors of the tongue and are abrasive. The lamina propria also contains lingual glands that make lingual lipase, a minor lipid-digesting enzyme.

SALIVA There are actually many salivary glands located in the mucous membranes of the tongue and mouth. They secrete saliva—about 1-1.5 liters per day. Its secretion increases during eating in order to coat the food that is ingested and to chemically break down the carbohydrates in food. There are many minor salivary glands and three pairs of major salivary glands. The submandibular glands are located on the floor of the mouth, secreting saliva via the submandibular ducts. The sublingual glands are beneath the tongue, secreting via the lesser sublingual ducts. The parotid glands are in the cheeks near the ears and secrete saliva via the parotid ducts. More than 95 percent of saliva is water. The rest is made from glycoproteins, enzymes, ions, and growth factors. Salivary amylase is made as part of saliva to start the breakdown process of carbohydrates. There are buffers by the phosphate and bicarbonate system that maintain a saliva pH of between 6.35 and 6.85 (slightly acidic). It lubricates food and assists in bolus formation. There is also IgA released to help fight off pathogens. Lysozyme is secreted as an antimicrobial agent. Some secreted saliva is high in mucus content. The act of salivation is under autonomic control and mainly stimulated by the parasympathetic nervous system, which aids in the production of saliva all the time. During sympathetic nervous system input, there is a decrease in the production of saliva, resulting in a dry mouth. The taste, smell, and sight of food will stimulate saliva production. Chemicals in food will stimulate the brainstem’s superior and inferior salivary nuclei, which send parasympathetic signals via the facial and glossopharyngeal nerves to increase salivation.

TEETH The teeth participate in the act of chewing food. They help mechanically digest food. There are 20 deciduous teeth or baby teeth and 32 permanent teeth or adult teeth. These include the following:

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Incisors—there are eight of these sharp front teeth used for biting into food.

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Cuspids—these are four canine teeth used to tear food up.

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Premolars—there are eight of these “bicuspids,” which are flatter for mashing up food.

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Molars—there are 12 of these on the side of the mouth for crushing food. Four of these are the wisdom teeth.

The teeth are located in the tooth sockets, also referred to as the alveolar processes, located in the mandible and maxilla bones. The gums or gingivae line these tooth sockets; they participate in a minor way in securing the teeth. The periodontal ligaments mainly secure the teeth to the socket. The crown is the part above the gum line, while the root is the part below the gum line. The outer layer is the enamel, which protects the pulp cavity (where the nerves and blood vessels exist), the root canal, and the dentin, which is like bone. Outside of the dentin is a harder layer called cementum. The hardest layer (and the hardest substance in the body) is the enamel. Figure 100 shows the anatomy of the tooth:

THE PHARYNX When it comes to the digestive system, only the oropharynx and laryngopharynx participate in digestion. The oropharynx is directly behind the mouth and is where the food first enters through the fauces and into the pharynx. The laryngopharynx is just above the larynx; the

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posterior aspect of this structure opens into the esophagus. The wall or lining of the oropharynx is the same as in the mouth with stratified squamous epithelium. During swallowing, there are elevating skeletal muscles that raise and expand the pharynx in order to make room for the food bolus. Then the constricting muscles contract so that the bolus of food can be swallowed. Food is forced into the esophagus and the act of esophageal peristalsis begins. The soft palate and uvula prevent the food from getting into the nasopharynx, while the epiglottis folds to prevent food from getting in the trachea. If it does, this will initiate a forceful cough reflex to bring food back up into the pharynx for proper swallowing.

ESOPHAGEAL ANATOMY The esophagus is about 10 inches in length and connects the pharynx to the esophagus, located just behind the trachea. It is collapsed until food enters it and follows a relatively straight course, penetrating through the diaphragm in order to enter the esophageal hiatus. There are two sphincters in the esophagus. The first is the upper esophageal sphincter, which is essentially the same as the inferior pharyngeal constrictor. It controls the amount of food that enters the esophagus from the pharynx. The upper two-thirds has both smooth and skeletal muscle fibers with essentially no skeletal muscle after the second third of the esophagus. There is peristalsis in the esophagus from the beginning. There are secretions that lubricate the esophagus and food as it passes. The second sphincter is the lower esophageal sphincter—called the cardiac sphincter or gastroesophageal sphincter. It is a muscular valve that contracts after food passes through and prevents food and stomach acid from getting back up into the esophagus. It opens to bring food into the stomach. Its dysfunction leads to gastroesophageal reflux disease or GERD. The histology of the esophagus involves the non-keratinized stratified squamous epithelium. This protects the esophagus from abrading food. The mucosa has a lamina propria that secretes mucus via mucus-secreting glands. The muscularis layer depends on where one is in the esophagus. The upper third is nearly all skeletal muscle, the middle third has both smooth 303

and skeletal muscle, and the lower third has only smooth muscle. There is no serosal layer but there is an adventitial layer. It is not covered by visceral peritoneum. The act of swallowing is called deglutition. It is the movement of food as a bolus from the mouth to the stomach. It takes about a second for liquids to pass through the esophagus and 4-8 seconds for solid or semisolid food to pass through. The process is not passive and involves a complex series of muscular activities that are both conscious and unconscious phases. The voluntary phase of swallowing is controllable. Chewing is over and the tongue moves upward and backward against the palate so that food can get into the oropharynx. There are muscles that kick in to prevent food from getting into the trachea or nasopharynx. The pharyngeal phase involves receptors in the oropharynx that sense food, sending it to the “deglutition center” in the medulla oblongata. Breathing stops briefly by the closure of the epiglottis and pharyngeal muscles constrict to move the bolus through the pharynx. The upper esophageal sphincter allows food to enter the esophagus. The esophageal phase involves peristalsis, controlled by the medulla oblongata. There are circular and longitudinal muscles that contract to push the bolus through. It is a short reflex that relaxes the lower esophageal sphincter to allow food to pass into the stomach.

STOMACH ANATOMY AND PHYSIOLOGY Chemical digestion starts minimally in the mouth but really advances in the stomach. The stomach links the esophagus to the small intestine. It contracts readily to cause mechanical digestion. It can stretch to more than 75 times its empty size in order to take in as much as four liters of food or fluid. It is also a receptacle for food, letting in only a little bit of food at a time into the small intestine. The food that is mixed with digestive juices is called chyme, which is made in the stomach. Little nutrient absorption occurs. The four main regions of the stomach are the cardia, the fundus, the body, and the pylorus. The cardia is the first part, located just after the esophagus. The next part is the fundus, which is dome-shaped. Below this is the main portion—the body. The pylorus is the last part, connecting the stomach to the duodenum. It is funnel-shaped, with the largest part being called the pyloric

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antrum. The narrower part is called the pyloric canal, with a pyloric sphincter muscle controlling stomach emptying. Without food, it collapses into folds of mucosa and submucosa, known as rugae. Figure 101 shows an image of what the stomach anatomy looks like:

Like the rest of the alimentary canal, there are four layers to the stomach wall. The muscularis layer and the mucosal layer have unique functions in the stomach. There is an inner oblique smooth muscle layer as well as the circular and longitudinal muscles. All of these allow for the churning of food in this organ. The mucosa has an epithelial lining that makes surface mucus cells that secrete a protective coating of alkaline mucus to protect the stomach wall. Gastric pits exist in the epithelium of the stomach that mark the entrance of gastric glands, which secrete gastric juices. The gastric glands of the cardia and pylorus mainly secrete mucus; however, the pyloric antrum makes both mucus and gastrin (a digestive hormone). The larger glands of the body and fundus make the most gastric juices. The different secretory cells of the gastric juices include the following:

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Parietal cells—these secrete both hydrochloric acid and intrinsic factor, responsible for the low pH (of 1.5-3.5) in the stomach. This low pH is necessary for pepsinogen to convert to the active pepsin and is necessary to kill pathogens. Intrinsic factor is a glycoprotein which facilitates the absorption of vitamin B12 in the small intestine.

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Chief cells—these make pepsinogen, which is the inactive “proenzyme” that uses hydrochloric acid to create pepsin, an enzyme that digests protein.

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Mucus neck cells—these mainly secrete mucus in the upper stomach. It is different from the mucus made by goblet cells as it is acidic in nature. It is not known what this mucus does.

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Enteroendocrine cells—these secrete hormones, including gastrin made by the G cells.

There are multiple hormones secreted by the stomach. The G cells of the pyloric antrum makes gastrin in response to the presence of protein and amino acids in the stomach. It increases gastric gland secretion, promotes gastric emptying, promotes small intestinal muscle contraction, relaxes the ileocecal valve, and causes mass movements in the large intestine. There is ghrelin (made in the fundus) during fasting that stimulates hunger. Histamine will increase parietal cell secretion of hydrochloric acid (HCl). Serotonin is made that will contract the stomach muscles. Somatostatin will, on the other hand, limit motility of the stomach, limit emptying, decrease intestinal absorption, and slow pancreatic secretions. There are neural inputs and endocrine inputs to gastric secretion of gastric juices. This leads to what’s known as cephalic, gastric, and intestinal phases of gastric secretion, which can occur simultaneously. The cephalic phase involves stimulation by the sight and thought of food and stimulation of taste and smell receptor that, through the cerebral cortex, hypothalamus, and medulla oblongata, will stimulate stomach secretions. Poor appetite will block stomach secretions. The gastric phase will involve gastric distention and rising pH levels from food that will stimulate gastric secretions or high acidity that will decrease gastrin secretion. The intestinal phase will be triggered by duodenal changes (distention and pH changes) that will increase or inhibit the secretory activity of the stomach.

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The cephalic phase is brief, while the gastric phase lasts about 3-4 hours. In the gastric phase, there is an upper limit of the amount of HCl produced in the stomach so that the HCl production will stop if the pH gets too low. The intestinal phase involves the release of intestinal gastrin, which first enhances gastric secretion. The distention of the duodenum, however, initiates the enterogastric reflex, which inhibits gastric secretion and closes the pyloric sphincter so that additional chyme will not enter the esophagus. The mucosal barrier protects the stomach from being digested by its own hydrochloric acid. This involves a thick bicarbonate-rich mucus barrier that acts as a physical and chemical barrier to HCl. There are tight junctions in the epithelium that also prevent gastric juices from passing through the epithelial wall. Stem cells will rapidly replace the lost or damaged epithelial mucosal cells so that the surface of the stomach will be replaced every 3-6 days. There is mechanical and chemical digestion taking place in the stomach. As for mechanical digestion, there is a “mixing wave” that is unique to the stomach. It mixes and softens food in order to make chyme. The force increases as the food passes through the stomach. The pylorus holds about an ounce of chyme, passing small amounts through the pyloric sphincter in what’s called “gastric emptying.” Only about three milliliters of chyme pass through the pylorus at a time. Chemical digestion includes some activity of salivary amylase, which is gradually inactivated as the stomach becomes more acidic. Lingual lipase is actually activated by the acidic environment of the stomach, breaking down triglycerides. Protein breakdown starts with pepsin activity. Intrinsic factor acts not on the stomach but on the small intestine to absorb vitamin B12. The stomach contents are completely emptied into the duodenum within 2-4 hours after a meal. Carbohydrates empty the fastest, followed by protein-laden foods. Fatty foods digest slowly and can stay in the stomach for at least six hours.

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SMALL INTESTINE The substance released from the stomach is called chyme. It enters the small intestine, which does most of the digestive function in the abdomen. Nearly all absorption happens as well in the small intestine. The small intestine is 10 feet in length with a one-inch diameter. The surface area is 200 square meters, necessary for the digestive and absorptive processes. There are three regions in the small intestine: the duodenum, the jejunum, and the ileum. The duodenum is just 10 inches in length. It starts at the pyloric sphincter and is largely retroperitoneal (behind the peritoneum); it is C-shaped to curve around the pancreas. It contains the ampulla of Vater, also called the hepatopancreatic ampulla, which is where the bile duct and the main pancreatic duct join to make the major duodenal papilla. This area has a sphincter called the sphincter of Oddi (hepatopancreatic sphincter) that regulates the release of bile and pancreatic secretions. The jejunum is three feet in length and is the middle section of the small intestine. It does not have a clear demarcation between it and the ileum. The ileum is the longest segment of the entire intestinal tract, being six feet in length. It ends at the ileocecal valve, connecting it to the cecum of the large intestine. The small intestine is innervated in two ways: by the vagus nerve, which leads the parasympathetic input, and by the thoracic splanchnic nerve, which leads the sympathetic input. Its vasculature comes from the superior mesenteric artery and drains through the superior mesenteric vein, which carries blood to the liver via the hepatic portal vein. The small intestine has the same four layers as the rest of the alimentary canal; however, the mucosa and submucosa are different and unique to this area. There are circular folds, villi, and microvilli that increase the surface area of the small intestine. The circular folds are deep ridges in the mucosa and submucosa, particularly in the duodenum and down to the mid-ileum. These facilitate absorption. They cause a spiral movement of chyme so that there is time for nutrients to be absorbed to the fullest. The villi are hair-like vascularized projections—about 20-40 villi per square millimeter. Each villus contains an

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arteriole, a venule, and a lacteal for the absorption of nutrients. Figure 102 illustrates the anatomy of the villi:

The microvilli are smaller than villi and are extensions of the epithelial cell membrane, supported by intracellular microfilaments. They cannot be seen by the naked eye with about 200 million of them per square millimeter. This hugely expands the surface area of the intestine. There are intestinal glands in the mucosa as well. These are also referred to as the crypt of Lieberkühn. These will make an alkaline intestinal liquid, which is a mixture of mucus and water. About 1-2 quarts are secreted when the intestines are filling with chyme. There are also duodenal glands called Brunner’s glands, which produce a highly alkaline substance to buffer the acids in the chyme coming out of the pyloric sphincter.

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Other cells include the goblet cells, which secrete mucus, Paneth cells, which secrete lysozyme (which is antibacterial), G cells (which produce intestinal gastrin), I cells (which make cholecystokinin to stimulate bile release and release of pancreatic juices), K cells (which secrete insulinotropic peptide that stimulates insulin release), M cells (which secrete motilin that accelerates gastric emptying, pepsin production, and intestinal peristalsis), and S cells (which secrete the hormone called secretin). There is mechanical digestion in the small intestine. It involves the process of segmentation and a phenomenon called migrating motility complexes. Segmentation involves the sloshing back and forth of intestinal chyme to allow for maximum absorption. This process is highest in the duodenum. After absorption, the segmentation process lessens and transport of chyme begins. This happens because of the duodenal secretion of motilin, which initiates the migrating motility complexes that force chyme through the small intestine slowly down the lumen. It takes about 90-120 minutes to pass through the small intestinal tract. There is a gastroileal reflex that is stimulated by the stomach and that enhances ileal segmentation and ileal motility, relaxing the normally-closed ileocecal valve. This all means that from the time of eating food to the time it leaves the small intestine is about 3-5 hours. The digestion of proteins and carbohydrates is only partly happening in the stomach. It is completed in the small intestine because of the actions of pancreatic juices and intestinal juices. The majority of lipids get digested in the small intestines via the action of bile and pancreatic lipase. Digestion also happens locally by the action of digestive enzymes released at the luminal surfaces of mucosal cells, near the microvilli, where both digestion and absorption can occur at the same time. This chemical digestion in the small intestine must take place in small amounts in order to maximize the process and avoid large influxes of water through osmosis into the intestinal lumen because of the hypertonicity (high concentration of substances) in the stomach chyme. This phenomenon is what occurs in “gastric dumping syndrome.”

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LARGE INTESTINE The large intestine is the end of the alimentary canal. Its main function is to complete the absorption of nutrients, absorption of water, vitamin synthesis, and the elimination of feces. It is a structure that starts at the appendix and ends at the anus. It is only about 3-feet long with a diameter of three inches. There are four regions to the large intestine: the cecum, colon, rectum, and anus. The start of the large intestine is the ileocecal valve, which controls the flow of chyme into the large intestine. The cecum is about six centimeters or 2.4 inches in length and contains the appendix. The appendix contains lymphoid tissue but is not considered a functional organ. The colon is divided into the ascending colon, transverse colon, descending colon, and sigmoid colon. There is right and left splenic flexure that act as “bends” in the upper right (hepatic side) and upper left (splenic side) of the colon. The rectum is about 8 inches in length and curves around the sacrum. There are three folds called the “rectal valves” that prevent the simultaneous passage of gas and feces. The anal canal has two sphincters, the smooth muscle internal anal sphincter (which is involuntary), and the skeletal muscle external anal sphincter (which is voluntary). There are no circular folds and no villi in the large intestine and there are few enzymes secreted. It consists of simple columnar epithelium (other than the anal canal), which is made from absorptive cells (called enterocytes) and interspersed goblet cells. Goblet cells secrete mucus that eases the passage of feces and protects the intestine from the effects of the acidic substances and gases made by the large intestinal bacteria. The major unique features of the large intestine are the bands of longitudinal muscle in the muscularis, divided into three parts called the teniae coli. When these muscles contract, they form the haustra, which are pouches that give the wrinkly appearance of the large intestine. Attached to the teniae coli are fat-filled sacs made by visceral peritoneum called epiploic appendages, which have no known function. These structures are seen in the entire colon except for the rectum and anal canal.

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The anal canal is made from stratified squamous epithelium that connects to the outside skin. This mucosa is stratified to counteract the abrasive forces of feces. The anus has mucosal folds called anal columns, that are highly vascularized. Between these folds are the anal sinuses that secrete mucus. Below the sinuses is the “pectinate line”—a horizontal line that is the connection point of the gut to the external skin. One of the unique things about the large intestine is the presence of trillions of bacteria in the lumen, called intestinal bacterial flora. There are hundreds of different kinds of pathogenic organisms living in the gut lumen. They facilitate chemical digestion and absorption and participate in vitamin synthesis. The main vitamins made are vitamin K, pantothenic acid, and biotin. Dendritic cells will continually evaluate the pathogenicity of these bacteria to ensure that the bacteria are not invasive or pathogenic. If pathogenic, an IgA-mediated immune response is generated so as to kill off any dangerous bacterial organisms. The large intestine receives the chyme, which contains a large amount of water and few nutrients. It takes 12-24 hours for the chyme to travel through the large intestine. Because it doesn’t have much in the way of nutrients, very little digestion occurs in this area. There is mostly mechanical digestion, caused by haustral contractions that is involved in segmentation. These are slow-moving contractions that aid in the absorption of water by the large intestine. In addition, peristalsis occurs in the large intestine as a “mass movement,” which quickly forces the distal contents of the colon through to the rectum. This occurs because of the gastrocolic reflex. There are no digestive enzymes secreted by the large intestine. The chemical digestion that does occur happens because of intestinal bacteria that ferment the remaining carbohydrates, giving off gases that create the flatus or gas in the large intestine. About 1500 milliliters of this gas is produced in the colon each day, with more produced when soluble dietary fiber and indigestible sugars are eaten by the individual. This is why beans cause excess flatus. The small intestine actually absorbs 90 percent of ingested water, with only 10 percent absorbed by the large intestine in the form of feces. Feces is made of unabsorbed nutrients, indigestible food particles, bacteria, water, old epithelial cells, and inorganic salts. Rectal

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muscles eliminate the feces, facilitated by the Valsalva maneuver (the bearing down that occurs when having a bowel movement). Mass movements force the feces from the colon into the rectum, provoking the defecation reflex, which eliminates feces in the rectum. When feces enter the anal canal, a voluntary action takes place, allowing for defecation. Mass movement can be blocked voluntarily but will come back after a period of time. Diet, overall health, and stress will determine the number of bowel movements that occur; the range is from 2-3 bowel movements per day to 3-4 bowel movements per week.

EXOCRINE PANCREAS The pancreas lies horizontally in the retroperitoneal area behind the stomach. Aside from its endocrine function, it also has exocrine functions which is the secretion of digestive enzymes that aid in the digestion of nutrients. There are pancreatic acini (which are grape-like cell clusters) that terminate in pancreatic ducts. They secrete pancreatic juices that exit the pancreatic system via the ampulla of Vater (or the hepatopancreatic ampulla). The sphincter of Oddi prevents the passage of these juices until they are needed. About a liter of pancreatic juice is secreted per day. It is slightly alkaline (with a pH of 7.1-8.2) that buffers the acidic gastric chyme. This will inactivate pepsin and create an environment for the pancreatic enzymes to work. There are enzymes for lipid, carbohydrate, and protein digestion. All of the secreted enzymes are inactive at the time of secretion. They only activate in the duodenum. There is an enzyme called enteropeptidase in the intestinal brush border that activates trypsinogen to make trypsin. This further activates proenzymes to make chymotrypsin and carboxypeptidase. There is also amylase, lipase, and nuclease that digest the nutrients in the food that is eaten. The secretion of enzymes from the pancreas is under hormonal and parasympathetic control. Acidic chyme in the duodenum triggers secretin release, which causes release of pancreatic juices. Proteins and fats in the duodenum also stimulate cholecystokinin release, which

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enhances pancreatic juice secretion. When the parasympathetic nervous system acts on these areas, there will be an increase in pancreatic secretion as well.

LIVER The liver is the largest gland in the body. It participates in digestion and metabolism and consists of two lobes: a larger right lobe and a smaller left lobe. There are several smaller lobes within the right lobe. There are multiple ligaments connecting the liver to the abdominal wall: the falciform ligament, the ligamentum teres hepatic, the coronary ligament, and two lateral ligaments. The lesser omentum is associated with the liver and the lesser curvature of the stomach. The hepatic artery and hepatic portal vein enter the liver at the porta hepatis. The hepatic artery delivers oxygenated blood to the liver, while the hepatic vein sends nutrients from the small intestine to the interior of the liver. Figure 103 shows the liver anatomy, including the passage of these vessels into the liver:

Nutrients are processed in the liver and released back into the bloodstream via the central vein, leading to the hepatic vein and the inferior vena cava. What this means is that all of the blood from the alimentary canal must first pass through the liver before it can be processed and sent back to the circulation.

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Within the liver, there are hepatocytes which account for 80 percent of the volume of the liver. These do much of the functioning of the liver. There are plates of hepatocytes radiating outward from the portal vein to make hepatic nodules. There are small ducts called bile canaliculi that attract bile from the hepatocytes. The bile flows through small ductules and larger bile ducts, ultimately ending up in the right and left hepatic ducts, which merge as the common hepatic duct. The cystic duct of the gallbladder combines with the hepatic duct to make the common bile duct. There are hepatic sinusoids, which are open blood spaces attracting blood from nutrient-rich hepatic portal veins as well as oxygenated blood from the hepatic arteries. These sinusoids have fenestrated capillaries that supply blood to the hepatocytes that can process nutrients, waste materials, and toxins. Bilirubin is processed in these areas with bile excreted into the bile canaliculi. The sinusoids, after processing of nutrients, send the blood out of the liver via the central vein. There are Kupffer cells in these sinusoids that phagocytize dead cells, foreign material, and bacteria. Bile produced by the liver help emulsify lipids in the small intestine so they can be more easily absorbed. About a liter of bile is produced each day. It contains bile pigments, phospholipids, cholesterol, triglycerides, bile salts, and water. It is the combination of bile salts and phospholipids, which are both polar and nonpolar. Their combination with lipids takes large lipid globules and turns them into small fragments that increase the surface area of the lipids for the digestive action of lipase to take place. Bile salts are recycled so they are used over and over. Bilirubin is the main pigment in bile and is a waste product of hemoglobin metabolism. It accounts for the green coloration of bile; however, it gets converted by intestinal bacteria into stercobilin, which is brown in color. Bile is stored between meals because it is not needed. The ampulla of Vater closes and bile is diverted into the gallbladder.

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GALLBLADDER The gallbladder is the storage organ for bile. It is about 3-4 inches in length and lies along the back and inferior aspect of the liver. It is muscular so that it can propel the bile from its interior, through the cystic duct, into the common bile duct, and finally into the duodenum. It is lined with simple columnar epithelium and has rugae much like is seen in the stomach; it has no submucosal layer. It is held against the liver by the visceral peritoneum that would normally be part of the liver. This peritoneal layer instead forms the outer layer of the gallbladder. It has the ability to concentrate the bile coming from the liver up to ten-fold.

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KEY TAKEAWAYS •

The alimentary canal is a four-layered structure throughout its course; the accessory organs participate in the digestive process.

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The mouth and teeth start the mechanical and chemical digestive process when food is first taken into the mouth.

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The stomach starts protein digestion and participates in carbohydrate digestion; the small intestine is the main organ for lipid digestion.

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Most absorption takes place in the small intestine, which is particularly designed to take up nutrients.

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The function of the large intestine is to make and transport feces, make a few vitamins, and absorb 10 percent of the total water in the chyme.

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QUIZ 1. What is the outermost layer of the wall of the GI tract? a. Mucosa b. Submucosa c. Muscularis d. Serosa Answer: d. The serosal layer or serosa is the outermost layer of the gastrointestinal tract. 2.

Which layer of the GI tract will contain the MALT tissue, important in the immune defense of ingested pathogens? a. Mucosa b. Submucosa c. Muscularis d. Serosa Answer: a. The MALT tissue is “mucosa-associated lymphoid tissue,” which is located in the mucosa and is responsible for immune defense in the system.

What is the mucous membrane of the mouth made of? a. Pseudostratified columnar epithelium b. Keratinized stratified cuboidal epithelium c. Simple squamous epithelium d. Nonkeratinized stratified squamous epithelium Answer: d. The mucous membrane of the mouth consists of nonkeratinized stratified squamous epithelium, which protects the mucosa against abrading foods.

Which muscle is considered an extrinsic tongue muscle? a. Hyoglossus muscle 318

b. Longitudinalis inferior muscle c. Transverse linguae muscle d. Verticalis linguae muscle Answer: a. The hyoglossus muscle is an extrinsic tongue muscle, while the other muscles listed are considered intrinsic muscles of the tongue. 5.

What kind of musculature exists in the lower third of the esophagus? a. A mixture of smooth and skeletal muscle b. Skeletal muscle only c. Smooth muscle only d. There are no muscles in this part of the esophagus Answer: c. There is smooth muscle only in the lower third of the esophagus. There is skeletal muscle in the upper third and a mixture of smooth and skeletal muscle in the middle third.

In the gross anatomy of the stomach, there are four separate sections. What is the first section of the stomach called? a. Cardia b. Pylorus c. Body d. Fundus Answer: a. The cardia is the first part of the stomach and is the part that first receives food.

Which enzyme plays the largest role in digestion of food in the stomach? a. Pepsin b. Salivary amylase c. Pancreatic amylase d. Lingual lipase

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Answer: a. While both salivary amylase and lingual lipase are active in the stomach, pepsin is the main enzyme that acts to digest the food, mainly protein, in the stomach. 8.

Which aspect of the alimentary canal is considered the longest part? a. Duodenum b. Ileum c. Colon d. Jejunum Answer: b. The ileum is the longest aspect of the alimentary canal, being about six feet in total length.

Which part of the alimentary canal contains the appendix? a. Transverse colon b. Ileum c. Cecum d. Sigmoid colon Answer: c. The cecum is the first part of the large intestine; it harbors the appendix, which is a largely vestigial organ, although it does contain lymphoid tissue.

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In the intestinal tract, what is the function of goblet cells? a. They secrete enzymes b. They make mucus c. They absorb nutrients d. They regulate acids and bases in the lumen Answer: b. The goblet cells are found in all parts of the intestinal tract and make mucus for the facilitation of the passage of substances and the protection of the GI tract from acids and the abrading effects of food.

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CHAPTER FOURTEEN: METABOLISM AND HUMAN NUTRITION This chapter covers the microscopic and molecular aspects of metabolic processes. Carbohydrate, protein, and lipid metabolism are discussed as well as the important energyproducing process of glucose metabolism. The overall physiology of human nutrition and nutritional needs in humans are also examined as part of this chapter.

THE PROCESS OF CHEMICAL DIGESTION Chemical digestion involves the breakdown of different types of food substances into subunits that are able to be absorbed by parts of the alimentary canal. The chemical reactions necessary for these larger substances to be broken down is known as “hydrolysis.” There are many different enzymes in the GI tract that participate in these chemical processes. While these have been discussed in the previous chapter, the following is a summary of these important enzymes: •

Lingual lipase—this is a salivary enzyme that breaks down triglycerides into free fatty acids.

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Salivary amylase—this is a salivary enzyme that breaks down polysaccharides into smaller sugars (like disaccharides and trisaccharides).

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Gastric lipase—this is a chief cell enzyme (from the stomach) that breaks down triglycerides into free fatty acids.

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Pepsin—this is a chief cell enzyme that breaks down proteins into peptides.

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Alpha-dextrinase—this is a brush border enzyme that breaks down alpha-dextrin molecules into glucose.

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Enteropeptidase—this is a brush border enzyme that takes trypsinogen and makes it into trypsin.

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Lactase—this is a brush border enzyme that breaks lactose down into glucose and galactose.

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Maltase—this is a brush border enzyme that breaks maltose down into glucose.

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Nucleosidases and phosphatases—these are brush border enzymes that break down nucleotides like DNA and RNA into phosphate and simpler molecules.

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Peptidases—this includes aminopeptidase (which knocks off amino acids) and dipeptidase (which breaks down dipeptides into amino acids).

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Sucrase—this is a brush border enzyme that takes sucrose and breaks it into glucose and fructose.

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Carboxypeptidase—this is a pancreatic enzyme that knocks off amino acids at the carboxyl end.

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Chymotrypsin—this is a pancreatic enzyme that breaks down proteins into peptides.

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Elastase—this is a pancreatic enzyme that breaks down proteins into peptides.

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Nucleases—these are pancreatic enzymes that break down RNA or DNA into nucleotides.

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Pancreatic amylase—this is a pancreatic enzyme that breaks down polysaccharides/starches.

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Pancreatic lipase—this is a pancreatic enzyme that breaks down triglycerides into fatty acids.

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Trypsin—this is a pancreatic enzyme that breaks proteins down into peptides.

CARBOHYDRATE DIGESTION The diet consists of about 50 percent carbohydrates. There are simple sugars (1-2 sugar molecules in a chain, called monosaccharides and disaccharides) and complex carbohydrates, also referred to as polysaccharides. The main monosaccharides are fructose, galactose, and glucose. These are easily absorbed. The main disaccharides are sucrose, maltose, and lactose. 322

The most common polysaccharides in the body are glycogen and starches. Cellulose is an indigestible polysaccharide that is not able to be utilized by the body. While digestion of carbohydrates starts in the mouth, most of the digestion takes place in the small intestine through the action of pancreatic amylase. The complete digestion of carbohydrates, however, depends on multiple brush border enzymes. For example, alphadextrinase acts on alpha-dextrin by knocking off one glucose molecule at a time. The three main disaccharides are further broken down into monomers (single units) by sucrase, lactase, and maltase, which are all brush border enzymes.

PROTEIN DIGESTION Proteins are basically chains of amino acids. Digestion takes proteins and breaks them down into amino acids again. About 15-20 percent of the caloric intake of the human diet is protein. The digestion of proteins begins in the stomach and ends in the small intestine. It begins with pepsin in the stomach, although the acidic environment contributes to protein breakdown. The pancreas contributes through the action of trypsin and chymotrypsin. The brush border enzymes like dipeptidase and aminopeptidase will result in small peptides and amino acids that can be absorbed.

LIPID DIGESTION Lipid intake is ideally less than 35 percent of the caloric intake. Most lipid intake is not cholesterol but is instead triglycerides, which is a molecule of glycerol connected to three fatty acids. There are three lipases that participate in the digestion of lipids. These start with lingual lipase and gastric lipase but mainly involves pancreatic lipase. In practicality, all lipid digestion takes place in the small intestine, breaking triglycerides into two fatty acid molecules plus a monoglyceride. These are taken up by the lacteals in the small intestine.

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NUCLEIC ACID DIGESTION While one doesn’t think that nucleic acids are nutrients, both RNA and DNA are found in most foods. Two types of nucleases exist in the pancreas: Ribonuclease (which digests RNA) and deoxyribonuclease (which digests DNA). These break the nucleic acids into nucleotides. These are acted on by the brush border enzymes, nucleosidase and phosphatase, which break down the nucleotides into pentose sugars, phosphate, and nitrogenous bases. Each of these can be absorbed by the enterocytes.

NUTRIENT ABSORPTION Once digested, nutrients need to be absorbed into the bloodstream by the enterocytes in the small intestine. Nearly all of ingested solid food, 90 percent of water, and 80 percent of electrolytes get absorbed within the confines of the small intestine. Most of the protein and carbohydrate absorption happens in the jejunum but vitamin B12 and bile salts get absorbed in the terminal ileum. What’s left for the large intestine are indigestible plant fibers and a small amount of water. There are five mechanisms of nutrient absorption: •

Active transport—this is the pumping of a substance up a concentration gradient and requires cellular energy.

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Passive diffusion—this involves the passage of a substance from a high concentration to a lower concentration that does not require energy.

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Facilitated diffusion—this is a diffusion process but it requires a transport or carrier protein to cross the cell membrane.

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Co-transport or secondary active transport—this involves the movement of a molecule from a high concentration to a lower concentration to power the movement of another molecule against a concentration gradient.

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•

Endocytosis—this involves the formation of vesicles by the cell membrane and requires cellular energy.

Water-soluble nutrients must use, at a minimum, a transport molecule. Nothing can pass between the cells because of tight junctions so everything must pass through the enterocyte. Once the substances are absorbed, the carbohydrates and the amino acids go into the hepatic portal vein, while the lipids diffuse across the cell membrane, get packaged into vesicles, and enter the lacteals that go directly through to the thoracic duct and finally to the venous system in the left subclavian vein. Carbohydrates need to be absorbed by monosaccharides. Both glucose and galactose are absorbed via cotransport with sodium ions, while fructose is absorbed via facilitated diffusion. They leave the enterocytes via facilitated diffusion. Amino acids get absorbed via active transport with up to 98 percent absorbed via the small intestine. Most amino acids require sodium active transport in order to be absorbed. Dipeptides and tripeptides get absorbed as well but are broken down to amino acids before entering the capillaries through diffusion. Lipids get absorbed through the help of bile salts. Short-chain fatty acids can enter via simple diffusion and leave via diffusion into the capillaries. Long-chain fatty acids are not as easily kept in the intestinal lumen by themselves. They are enclosed in micelles with the help of lecithin and bile salts. Fat soluble vitamins and cholesterol are in the center of these micelles. These squeeze between the microvilli and get absorbed into the enterocyte via simple diffusion. They get reincorporated into triglycerides and get surrounded with proteins to make a water-soluble chylomicron that enter the lacteals. Nucleic acids are broken down significantly into pentoses, nitrogenous bases, and phosphate ions. These enter the enterocyte via active transport and ultimately leave the enterocyte the same way to get into the bloodstream. Most minerals get absorbed completely, even if they are not needed. The exceptions are iron and calcium. Iron enters via active transport and gets stored in the ferritin protein until needed. They get lost to the lumen of the GI tract as the enterocytes get sloughed off if iron 325

isn’t needed. If needed, they enter the bloodstream and get transported on transferrin. In the case of calcium, PTH is secreted by the parathyroid glands if the calcium concentration is low. It requires active vitamin D in order to have calcium absorbed. The small intestine absorbs vitamins fat-soluble vitamins (vitamins A, D, E, and K) in the micelles via simple diffusion. It takes dietary fats to help this happen. B vitamins and vitamin C are water-soluble but still get absorbed via simple diffusion (except for vitamin B12, which requires intrinsic factor and endocytosis to be absorbed).

METABOLISM Metabolism is the sum of all chemical reactions involving catabolism (breakdown of substances) and anabolism (the building of substances). The digestion of food is catabolic because larger molecules get broken down into smaller molecules. Anabolism happens when proteins and larger molecules get build from their component parts. Catabolic reactions will produce energy, while anabolic reactions use up energy.

CATABOLIC REACTIONS Catabolic reactions involve the breakdown of large molecules into their constituent parts— processes that release energy. About 40 percent of this energy goes to making the main energy molecule of cells, which is ATP. ATP is used to drive many cellular processes and is the main supporter of organ function. It aids in contracting muscles, in nerve functioning, and in absorbing food from the GI tract. The rest of the energy produced (60 percent) is given off as heat, which is where body heat comes from. Carbohydrates are the most common energy source in the body, making up half of the diet. Sugar breaks down into monomers (monosaccharides). Glucose is the monosaccharide that is most used in making ATP, with extra glucose stored as an energy reserve in both the liver and the skeletal muscles. The storage form of glucose is glycogen. When enough glycogen is made, the rest of glucose is converted into triglycerides and is stored in body fat. Triglycerides are the most common fat source of energy, with about half of excess fat being stored in the subcutaneous tissues of fat. The rest is stored in internal body fat. Proteins get 326

broken down into amino acids to make other proteins. There is no storage form of protein. There is also no storage form of nucleic acids.

ANABOLIC REACTIONS Anabolic reactions involve the creation of larger molecules from smaller molecules. It involves things like making glycogen or larger polysaccharides from monosaccharides, the creation of triglycerides from fatty acids, the making of proteins, and the manufacture of nucleic acids from nucleotides. Each of these processes require the use of ATP that has been made through catabolic reactions. The process of anabolism is also referred to as the process of “biosynthesis.”

HORMONES THAT REGULATE METABOLISM There are hormones of the body that will participate in the decision to have anabolic reactions happen or catabolic reactions happen. Catabolic hormones include glucagon, cortisol, epinephrine, and cytokines. Anabolic hormones include growth hormone, insulin, insulin-like growth factor, estrogen, and testosterone. These hormones can be summarized as follows: •

Cortisol—this is released by the adrenal cortex and participates in breaking down glycogen into glucose as well as breaking down proteins and fats.

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Glucagon—this is released by the alpha cells of the pancreas and participates in breaking down glycogen into glucose in order to raise the glucose levels. It acts in direct opposition to insulin.

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Adrenaline—this is release by the adrenal medulla and stimulates gluconeogenesis to make more glucose in times of need during the fight-or-flight response.

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Growth hormone—this is an anabolic hormone that stimulates the growth of tissues, cells, and bony tissue.

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Insulin-like growth factor—this stimulates muscle and bone growth and blocks apoptosis (or programmed cell death). 327

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Insulin—this is produced by the beta cells of the pancreas and promotes the formation of glycogen from glucose; glycogen is the main storage form of glucose.

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Testosterone—this is produced in the testes or ovaries and stimulates an increase in muscle mass and muscle strength as well as bone growth.

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Estrogen—this is produced in the ovaries, adrenal gland, and liver; it is anabolic by increasing fat deposition.

OXIDATION-REDUCTION REACTIONS These types of reactions are important for all of metabolism. Both of these reactions involve the exchange of electrons in a chemical process. They either involve the splitting of hydrogen into a hydrogen ion (which is positively charged) and an electron. Oxidation involves the loss of an electron from hydrogen—a process that releases energy. This energy plus the electron are passed on to another molecule in a chemical process called reduction (the gain of an electron). Because electrical charge must always stay the same, oxidation reactions and reduction reactions occur together so there are no free electrons floating around. This combination is called a “redox reaction.” They happen in a chemical sequence with the energy from oxidation reactions stored in the molecule that participates in the reduction reaction. Common redox reactions that occur are those that make ATP (and energy) from ADP, that make nicotinamide adenine dinucleotide (NAD) into NADH, and that make flavin adenine dinucleotide (FAD) into FADH2. Both NADH and FADH2 are lesser-known energy-producing molecules that use their energy to make more ATP, which is the main energy source for reactions in the body.

CARBOHYDRATE METABOLISM Carbohydrates are only made from carbon, oxygen, and hydrogen. As food, both complex carbohydrates and simple carbohydrates can be consumed. Simple carbohydrates include glucose, galactose, and fructose, while complex carbohydrates include cellulose, glycogen, and starch. Polysaccharides or complex carbohydrates are molecules that both store energy and act as structural molecules (consider the structural effect of cellulose in plants). 328

The enteric digestive process involves the breakdown of complex carbohydrates into simple sugars, which are absorbed and distributed. Once the simple carbohydrate is taken up by the cell, it is used for energy production in a process known as cellular respiration. There are three main components to cellular respiration but the focus of each of these is to break down glucose into what becomes carbon dioxide and water—a process that creates energy. Different parts of the cell participate in the different cellular respiration processes. The first step is known as glycolysis. This is a simple process that starts the breakdown of glucose and produces some energy. It takes place in the cytoplasm of the cells as a multistep process. Figure 104 shows what happens in glycolysis:

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Glycolysis starts with the addition of a phosphate group by the enzyme hexokinase to produce glucose-6-phosphate. It uses up an ATP molecule; however, this will be “regained” in the end. Then, phosphofructokinase takes the glucose-6-phosphate and makes fructose-6-phosphate. Another ATP molecule is then sacrificed to make fructose-1,6-bisphosphate. It gets split and modified to form two molecules of glyceraldehyde-3-phosphate. They get another phosphate added to them to make 1,3-bisphosphoglycerate. Each of the 1,3-bisphosphoglycerate molecules becomes pyruvate with the four phosphate groups added to make a total of four ATP molecules. Through this pocess there is a net addition of two ATP molecules. In addition, two NADH molecules are made, which are used later. There are two hydrogen ions left over that get used later as well. While this is technically an energy-producing process, note that it uses no oxygen and that it doesn’t fully break down glucose. The pyruvate, however, becomes an important part of aerobic respiration. If no oxygen is present to participate in aerobic respiration, the pyruvate molecules must go through an anaerobic respiration process. In this pathway, pyruvate molecules get converted into lactic acid. This will generate one additional ATP molecule but still doesn’t fully break down glucose. The reason for this anaerobic pathway occurring (besides making ATP) is that the glycolysis pathway can only move forward with the pyruvate concentration being as low as possible. Rather than using oxygen, lactic acid is the acceptor of the leftover electrons formed in glycolysis. Anaerobic respiration occurs in every cell of the body, even those (like erythrocytes or RBCs) that do not have mitochondria, which are necessary for aerobic respiration to occur. This is an effective way of making ATP but it can only be sustained for a few minutes. This is why anaerobic exercise lasts only a short time. The lactic acid produced must diffuse out of the cell and into the bloodstream, where it goes to the liver. There is a Cori cycle in the liver that turns the lactic acid back into pyruvate or glucose, starting the process all over again. Aerobic respiration involves the use of oxygen that becomes the final electron receptor and serves to turn the pyruvate generated from glucose into CO2 and water. The process takes

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place in the mitochondria and involves the Krebs cycle, which is also referred to as the citric acid cycle or the tricarboxylic acid cycle. Figure 105 describes the Krebs cycle:

The Krebs cycle produces more ATP, NADH, and FADH2. The ATP gets used directly for energy processes, while the NADH and FADH2 go on to pass electrons through what’s called the “electron transport chain” in the mitochondria. It is the electron transport chain that ultimately produces the most ATP out of the original glucose molecule. It is called a “cycle” because it reuses molecules until CO2 is produced. Each turn of the Krebs cycle makes one ATP molecule, three NADH molecules, and one FADH2 molecule.

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Next comes the electron transport chain. This occurs the inner mitochondrial membrane and involves multiple complexes of enzymes that shift electrons down the chain of molecules, using the energy stored in NADH and FADH2 to make ATP energy instead. The process uses chemical reactions called “oxidative phosphorylation” and requires oxygen. In the process, ADP is phosphorylated (meaning it has a phosphate chain attached to it) to make ATP and oxygen is combined with hydrogen ions and electrons to make water. Inside the mitochondrial inner membrane, which is where the electron transport chain is, is an enzyme complex known as ATP synthase. Powered directly by the flow of hydrogen ions through the membrane and into the mitochondrial matrix, this enzyme complex makes ADP and phosphate into ATP. This is a very highly energy-producing process. If glycolysis, the Krebs cycle, and the electron transport chain are put together, the net gain of ATP molecules in aerobic respiration per glucose molecule is 36.

GLUCONEOGENESIS This is the production of new glucose molecules, which can be directly made from pyruvate, alanine, glutamine, lactate, or glycerol. Note that only two amino acids (alanine and glutamine) can directly make glucose. This can happen in the liver only if there is insufficient glucose or carbohydrates in the diet. The reason this is essential for the human body is that the brain can only use glucose for energy so it needs to be present in sufficient amounts for the brain to function. While pyruvate is essentially the starting point for gluconeogenesis, it is not the reverse process of glycolysis. It first involves the conversion of pyruvate into oxaloacetate, which gets enzymatically converted to phosphoenolpyruvate or PEP. After this, the process is much like the reverse of glycolysis but, of course, there are different enzymes involved. Glucose-6phosphatase, for example, is one of the last enzymes used to make glucose.

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LIPID METABOLISM As mentioned, the main fats taken in by the diet are triglycerides. Triglycerides can also be made from carbohydrates that are not used in metabolism (when you eat more calories than you need). If, on the other hand, you need to use the energy from fats to participate in cellular processes, it is tied in with glucose metabolism so that energy can be created. The absorption of fats requires bile salts, pancreatic lipases, and the hormone cholecystokinin or CCK. This hormone stimulates pancreatic lipase secretion and the contraction of the gallbladder so that bile salts are available for lipid absorption. Interestingly, CCK also goes to the brain and will suppress hunger, which is why a fatty meal can suppress hunger more than a high-protein or high-carbohydrate meal. When lipids are broken down into fee fatty acids, they enter the enterocyte and reform into triglycerides. It is these triglyceride molecules that get packaged with cholesterol to make chylomicrons, that allow lipids to travel in aqueous environments. The chylomicrons can leave via exocytosis, where they can enter the lacteals in the lymphatic system. They can ultimately get processed by the liver or made into fat in the adipocytes. As mentioned, it is possible to gain energy from fat. The triglycerides must undergo hydrolysis in order to make glycerol and free fatty acids. This is known as lipolysis; it takes place within the cytoplasm of the cell. These fatty acids get oxidized to make acetyl CoA, which is directly fed into the Krebs cycle. The glycerol goes into the glycolysis pathway and proceeds toward the Krebs cycle as well. Each triglyceride molecule makes three fatty acids and one glycerol molecule; each fatty acid has as many as sixteen carbon atoms in it. This means that gram for gram, triglycerides yield more energy than either protein or carbohydrates, accounting for about nine calories per gram. If too much acetyl CoA is made from the oxidation of fatty acids and the Krebs cycle is overloaded, the acetyl CoA becomes a ketone body. Ketones can be used as a fuel source if there isn’t enough glucose. This is the case in prolonged starvation or when the person is a severe diabetic and isn’t using glucose properly for fuel. The end result is what’s known as

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“ketosis.” The excess acetyl CoA becomes a molecule called HMG CoA, which goes to make beta-hydroxybutyrate, the main ketone body found in blood. Ketone bodies can be used by the brain for energy in situations of very low glucose in the system. The ketones are broken down and metabolized to make carbon dioxide and acetone. The acetone is released from the body by being exhaled through the breath. This is why people in ketosis have an alcohol-like smell to their breath. The downside of this ketone metabolism is that it causes acidification of the bloodstream which, in diabetics, is called diabetic ketoacidosis.

LIPOGENESIS The process of lipogenesis happens when there is enough glucose around and more acetyl CoA than is necessary to go through the Krebs cycle. Fatty acids, cholesterol, steroids, triglycerides, and bile salts can be made from this substance. It happens in the cytoplasm of both liver and fat cells. Most of the acetyl CoA comes from glucose consumption and glycolysis and not from fat consumption. Molecules of acetyl CoA are strung together to make fatty acids of variable lengths. It requires the use of ATP to create these chemical bonds but creates a high-energy substance that is stored until it becomes necessary.

PROTEIN METABOLISM The main structural component of the human body is protein. Proteins make up nearly every major structural component of the cells of the body and makes things like enzymes, hemoglobin, collagen, and signaling molecules. Proteins have no storage molecule like carbohydrates and fats so, if taken in excess, they must be converted into triglycerides or glucose for storage or energy use. While most amino acids can be directly synthesized, this is not usually necessary because these can be consumed in food. Protein digestion starts with the denaturation of the protein molecule by hydrochloric acid and pepsin in the stomach. Chyme in the intestine will cause the release of secretin and cholecystokinin, which will cause pancreatic enzyme release and bicarbonate release. The enzymes trypsin, elastase, and chymotrypsin will further break down the protein pieces. The 334

end result is the absorption of amino acids that get used, converted into fats, or turned into acetyl CoA for the Krebs cycle. The process of breaking down proteins into amino acids is called proteolysis. The urea cycle takes the nitrogenous waste products that come from the breakdown of amino acids and turns it into a molecule that is safer in the body than the ammonium ions made in amino acid breakdown. This cycle occurs in the liver and the kidneys. Since the amino group in the amino acid is not a part of any metabolic pathway, to become a metabolically-active substance it must undergo transamination, which turns the amino group into a keto group. This creates a molecule that can enter the Krebs cycle plus an ammonium ion that goes into the urea cycle. While in the urea cycle, ammonium goes along with CO2 to make urea and water; the urea is excreted by the kidneys. Amino acids can be metabolized into several different molecules, including acetyl CoA, pyruvate, oxaloacetate, acetoacyl CoA, and alpha-ketoglutarate. Each of these can participate somewhere in the basic metabolic processes in the body that lead to the Krebs cycle and aerobic metabolism.

BASIC HUMAN METABOLISM Food gets absorbed during eating, used or stored as necessary, and then metabolized during times when a person isn’t eating. In other words, you don’t have to eat continually in order to have nutrients readily available. Right after eating, the body is in an absorptive state. The food is digested and transported into the body via the enterocytes. The sugars, amino acids, and lipids go to the liver, adipose tissue, or muscle tissue in order to be processed and used for energy. This absorptive state can last for up to four hours; insulin is released in order to put glucose into the muscle cells, fat cells, and liver cells. Glucose gets immediately turned into glucose-6-phosphate, which means there is a concentration gradient that pushes more glucose into the cell. Liver glucose goes to make glycogen; the same is true of muscle glucose that isn’t directly needed.

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The post-absorptive state is when the food has already been digested, absorbed, and stored. The body can use glycogen that was previously made in order to maintain a normal glucose level. There is less storage of fats and sugars (as insulin production is decreased) and more production of glucose under the influence of glucagon. Gluconeogenesis also occurs in the liver to make more glucose molecules to replace the depleted glycogen stores. Once this is done, the liver will convert leftover glucose into fat. During starvation or prolonged fasting, the immediate priority is to make glucose for the brain. The second priority is to conserve amino acids to make proteins. The body will use ketones for fuel and glycolysis is shut down in order for cells to use alternative fuels. Muscles will use fatty acids rather than glucose for fuel by being converted into acetyl CoA (to go into the Krebs cycle). The alanine, lactate, and pyruvate will not go into acetyl CoA in the muscle cells but will go to make necessary glucose in the liver. As starvation continues, ketone bodies get used for fuel in the heart and major organs. Fatty acids and triglyceride stores will be used to make ketones. This helps spare proteins from being used up to make glucose molecules. If this source of fuel is used up as well, the proteins from muscles are broken down to make glucose. This means that survival is dependent upon the amount of protein and fat stored in the body. The process of thermoregulation is keeping the body temperature within certain boundaries. The core body temperature is maintained within 97.7 and 99.5 degrees Fahrenheit. About 60 percent of the energy in the ATP production process is used to maintain the body temperature. The hypothalamus in the brain is highly involved in the regulation of body temperature. If the temperature is too high, there are mechanisms in place to lower the temperature. There is more heat dissipated through the skin surface. On the other hand, if there is a sensation of low body temperature, shivering will generate some heat. Thyroid hormone will also generate more heat through metabolic processes in order to gain more body heat. Heat can be lost from the body, flowing from a high heat area to a low heat area. This is done via several mechanisms: 1) Conduction (the direct transfer of heat between two objects, accounting for 3 percent of heat loss; 2) Convection (the transfer of heat through the skin,

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accounting for 15 percent of body heat loss); 3) Radiation (the transfer of heat through radiation to the environment, accounting for 60 percent of body heat loss); 4) Evaporation (the transfer of heat through the evaporation of water or sweat, accounting for 20 percent of body heat lost). The basal metabolic rate or BMR is the daily energy expenditure by humans at rest in the postabsorptive state and in a neutrally temperate environment. About 70 percent of all daily energy expenditure comes in the form of basal metabolic functions, 20 percent comes from physical activity, and 10 percent comes from body thermoregulatory processes. The BMR goes down when lean muscle mass is lost and with age.

NUTRITION AND METABOLISM The energy used and needed by the body involves what’s called the “nutritional calorie.” This is the amount of heat necessary to raise a kilogram of water by 1 degree Celsius. Approximately 1500-2000 calories per day are necessary to sustain daily activities—but it depends on body mass, gender, height, age, and activity level. More calories are required in situations of more activity. An extra 3500 calories per day are required to gain a pound of weight. The reverse is true when one wants to lose weight. Surprisingly, very little calories are burned in exercise. An example is jogging. One full mile of jogging will burn just 100 calories. Carbohydrates require the least amount of energy to process, while the processing of proteins requires the most energy. The balance of weight depends on what is taken in, how many calories are taken in, and how much energy is expended. The body mass index or BMI is a measure of the weight-to-height ratio and is a calculation used to determine a person’s level of obesity. A normal BMI is between 18 and 24.9 kg/m2. Being overweight involves a BMI of between 25 and 29.9 kg/m2, and being obese is a BMI of greater than 30 kg/m2. Being overweight or obese is associated with an increase in many types of diseases, ranging from type 2 diabetes to heart disease and certain cancers. Vitamins are a variety of organic molecules needed in biochemical processes but that are generally not synthesized de novo by the body. When it comes to metabolism, the B vitamins

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play the largest role. Some vitamins are directly taken in by the body through food, while others are made from food-related compounds, such as the synthesis of vitamin A from beta-carotene in vegetables. There are fat-soluble vitamins and water-soluble vitamins. Most fat-soluble vitamins are absorbed in the small intestine except that vitamin D is both absorbed and synthesized via UV light exposure. Water-soluble vitamins (the B vitamins and vitamin C) are absorbed in food. Minerals are inorganic compounds in food that cannot be made in the body. The main minerals in the body include sodium, potassium, phosphorus, calcium, chloride, and magnesium, which make up four percent of the total body mass. Calcium and phosphorus are the most common minerals in the body, being part of the human skeleton. Sodium and potassium are ionic electrolytes that are important in the regulation of all cellular structures. Iron is crucial to hemoglobin synthesis. There are many trace minerals that have low concentrations but have important biochemical properties. Important trace minerals include iron (used in ATP production and oxygen transport), zinc (used in immunity, blood clotting, and hormone functioning), copper (used in RBC production, collagen formation, immune function, and as an antioxidant), iodine (used in thyroid function), sulfur (used to make amino acids), fluoride (used for bone and tooth structure), manganese, cobalt (a part of vitamin B12), selenium, chromium, and molybdenum.

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KEY TAKEAWAYS •

Nutrients are digested, absorbed, and then metabolized by cells of the body.

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The main nutrient used in metabolism is the carbohydrate, which goes to glucose and its subsequent breakdown.

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There is glycolysis, aerobic respiration via the Krebs cycle, and the electron transport chain—all of which create total of 38 ATP molecules per glucose molecule.

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Proteins and lipids can be used in metabolism but ultimately go through glycolysis and/or the Krebs cycle.

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Vitamins and minerals are taken in the body because they can’t be synthesized and are used in various structural and biochemical processes.

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QUIZ 1. In the small intestine, there are brush border and pancreatic enzymes. Which of these enzymes are made by the pancreas? a. Enteropeptidase b. Trypsin c. Maltase d. Aminopeptidase Answer: b. Trypsin is a pancreatic enzyme, while the others are considered brush border enzymes. 2.

Which digestive enzyme preferentially acts on carbohydrates? a. Amylase b. Trypsin c. Lingual lipase d. Elastase Answer: a. Amylase is the only one of these enzymes that preferentially acts on carbohydrates. Lingual lipase acts on lipids, while trypsin and elastase act on proteins/peptides.

There are several kinds of absorptive mechanisms. The mechanism that requires the least amount of energy to cause absorption is what? a. Facilitated diffusion b. Co-transportation c. Active transport d. Endocytosis Answer: a. Each of these will require cellular energy; however, facilitated diffusion generally does not require ATP or similar energy sources to engage in the process.

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Some vitamins get absorbed via micelles because they are fat-soluble. Which vitamin is not absorbed this way because it is not fat-soluble? a. Vitamin K b. Vitamin A c. Vitamin C d. Vitamin E Answer: c. Each of these is a fat-soluble vitamin (along with vitamin D); however, vitamin C is water-soluble.

Which of the following is an anabolic reaction? a. The synthesis of glycogen from glucose b. The making of galactose and glucose from lactose c. The making of pentose and phosphate from deoxyribonucleic acid d. The creation of amino acids from a protein molecule Answer: a. The synthesis of glycogen from glucose takes a smaller molecule and “builds” a larger molecule. This is an anabolic reaction. The rest of the reactions involve breaking down larger molecules into their constituent parts, which are catabolic reactions.

Which hormone is in direct opposition to the anabolic action of insulin? a. Cortisol b. Glucagon c. Epinephrine d. Growth hormone Answer: b. Glucagon participates in gluconeogenesis, which involves making glucose out of glycogen. This acts in direct opposition to insulin and is activated when the glucose level is low.

Which molecule is not an energy-producing molecule? a. ATP 341

b. GDP c. FADH2 d. NADH Answer: b. Each of these is a highly reduced molecule that has stored energy within the molecule; however, GDP is not as reduced and is not generally used for energy production. 8.

What molecule is not an end-product of glycolysis? a. Lactic acid b. NADH c. ATP d. Pyruvate Answer: a. Each of these is an end-product of glycolysis in the cytoplasm of cells, except for lactic acid, which is a byproduct only if aerobic respiration does not occur.

Which hormone is most involved in the absorption of lipids in the digestive tract? a. Cholecystokinin b. Ghrelin c. Gastrin d. Somatostatin Answer: a. The hormone cholecystokinin helps trigger gallbladder contractions to release bile salts and will cause the release of pancreatic lipase. Additionally, it goes to the brain in order to act as an appetite suppressant.

10.

Fatty acids can be used to generate energy through aerobic metabolism. What molecule is made by fatty acids that enters the aerobic metabolic process? a. HMG CoA b. Pyruvate c. Acetyl CoA

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d. Glycerol Answer: c. Free fatty acids get oxidized in the cytoplasm to make acetyl CoA, which enters the Kregs cycle in order where it participates in aerobic metabolism

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CHAPTER FIFTEEN: URINARY SYSTEM The urinary tract includes the kidneys, ureters, bladder, and urethra. The anatomy and physiology of the kidneys are discussed in this chapter as well as the microscopic anatomy of these structures. Closely connected to the anatomy is the unique physiology of the kidneys, specifically the creation of urine.

URINARY TRACT ANATOMY The urinary tract involves the kidneys, ureters, bladder, and urethra. Urine is first made by the kidneys and stored in the bladder over time. Other than the kidneys, each of the other structures have mainly macroscopic, visible features and do assist with the creation of urine.

URETERS The ureters, like the kidneys, are retroperitoneal structures. They drain into the bladder, which is only covered with peritoneum on the dome of its structure. Urine drains into the calyces of the kidney and then into the renal pelvis, which is funnel-shaped. As each hilum narrows, it becomes a ureter. Urine is not passively drained through the ureters via gravity; instead, there are peristaltic waves that propel the liquid. They are not straight tubes but curve outward and then come inward to enter the bladder from an oblique angle. This oblique angle creates a one-way valve—that isn’t an actual sphincter but is physiologically a blockage to upward urine flow. Some children are born without this oblique insertion and suffer from vesicoureteral reflux or backward flow, which increases the risk of kidney infections. The ureters consist of specialized transitional epithelium, which is depicted in figure 106. There are a few mucus-secreting goblet cells within the epithelium. There are circular and longitudinal muscle fibers that contract in a peristaltic fashion. An adventitial layer covers the ureters and affix these structures to both the parietal peritoneum and the back of the abdominal wall:

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BLADDER The bladder is the collection organ for urine. The bladder sits in front of the uterus in women and behind the pubic bone. It also sits in front of the rectum. Figure 107 illustrates what the female urinary bladder looks like in situ:

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In women, the bladder can be compressed by the expanding uterus in pregnancy, leading to an increased frequency of urination. In men, absent the uterus, the bladder has similar anatomy except that the prostate gland sits beneath the bladder and around the urethra. As mentioned, most of the bladder is retroperitoneal except for the upper dome of the structure. The bladder wall is relatively thin, making it highly able to stretch. Still, there is a muscular layer (involving smooth muscle) called the detrusor muscle. This involves non-structured bands of smooth muscle that act to compress the structure as it empties. Its inner lining is the transitional epithelium, so called because it switches from the resemblance of columnar epithelium when the bladder is empty to the resemblance of stratified squamous epithelium when the bladder is full. The normal bladder capacity rangins from 400 – 600 milliliters of urine.

MICTURITION REFLEX This is a reflex involving the act of voiding urine. It involves a mixture of voluntary and involuntary activity. The reflex starts with bladder distension and begins to kick in when the bladder volume is about 150 milliliters. The voluntary control over urination involves keeping the external urethral sphincter from relaxing as the bladder continues to fill. Ultimately, the bladder’s capacity becomes so great that the urges must be attended to. This happens as the urine volume in the bladder is between 300 and 400 milliliters. Failure to maintain this and to overcome the bladder volume increase becomes “incontinence.” There are stretch receptors in the bladder wall that send signals to the sacral spinal cord. This is a short reflex that results in parasympathetic outflow from the spine that contracts the detrusor muscle and relaxes the internal urethral sphincter. This reflex can be overridden by children and adults because of control by the external urethral sphincter. Because this is a local reflex, individuals with paralysis can still have some control over their bladder. The nerves necessary for urinary control include the pelvic, hypogastric and the pudendal nerves. Voluntary control over voiding, however, requires the spinal cord to be intact. The pudendal nerve comes from the sacral micturition center. This manages the skeletal muscles that control the external urinary sphincter and therefore, controls continence. There is

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sympathetic input via the hypogastric nerve that blocks the contraction of the detrusor muscle. At some point, sensory nerve fibers from the pelvic nerve will activate the parasympathetic neurons that sends out motor fibers that contract the bladder muscle.

URETHRA The urethra is responsible for the transport of urine from the bladder to the outside of the body. It is clearly a different structure in males versus females. The base of the bladder is a triangular area called the trigone, with the urethra emptying at the apex of the triangle, below the symphysis pubis. Proximally, the lining of the urethra involves transitional epithelium, while the external portion is made from non-keratinized, stratified squamous epithelium. Only in males is there pseudostratified columnar epithelium between these two types of epithelia. There are two sphincters involved in the urethra: the internal urinary sphincter, which is under autonomic nervous system control (via the parasympathetic nervous system), and the external urinary sphincter, which is a voluntary muscular structure. The female external urethral orifice is actually imbedded within the anterior vaginal wall between the labia minora. It is about four centimeters in length, and the pudendal nerve being responsible for voluntary control over the sphincter. This is a sacral nerve, arising in the S2-S4 nerves coming out of the sacral nerve plexus. The male urethra is much longer than in females, being 20 centimeters in length. It is a bit more complex because it serves sexual and urinary functions. There are four separate regions to the male urethra: 1) the pre-prostatic urethra, 2) the prostatic urethra, 3) the membranous urethra, and 4) the penile/spongy urethra. The prostatic urethra is the part that passes through the male prostate gland. It receives sperm from the ejaculatory ducts and secretions from the paired seminal vesicles. Also paired glands are the Cowper’s glands (also called the bulbourethral glands), which secrete mucus that buffers the urethral pH to protect the sperm. The mucus lubricates the interior of the urethra and the buffering system serves to alkalinize the spermatic environment.

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The membranous urethra passes through the perineal muscles and involves the urethral sphincters. Past that is the spongy urethra that exits at the external urethral orifice after passing through the corpus spongiosum. There are mucous glands along the entire length of the urethra, which lubricate and buffer the tissues from changes in the pH of the urine. The pudendal nerve acts in males the same way it does in females by innervating the external urethral sphincter.

GROSS KIDNEY ANATOMY The kidneys are paired organs lying on either side of the spine. These are retroperitoneal structures that are pressed against the posterior aspect of the abdominal wall. There is a great deal of vascularity involved with the kidneys, largely because they filter the blood to make urine. They are not in the same position in the body with the left kidney at T12-L3 and the right kidney below that. The weight of the kidneys is 125-175 grams in men and 115-155 grams in women. The kidneys are extremely well protected. The lower ribs protect the upper portion; there is a dense fibrous capsule made of connective tissue; there is a renal fat pad that protects the entire structure; the fat pad is covered with renal fascia, which further protects them. This fascia and the peritoneum anchors the kidneys to the posterior abdominal wall so they are retroperitoneal. The adrenal glands sit atop each kidney. The internal anatomy of the kidneys involves the renal cortex, which is the outer region, and the medulla, which is the inner region. Figure 108 shows the internal anatomy of the kidneys:

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There are renal columns that are connective tissue extensions radiating down from the cortex into the medulla, separating the renal pyramids and renal papillae. The renal papillae are groups of collecting ducts, which transport urine made by the nephrons of the kidneys to the calyces of the kidney, which excrete the urine. There are 6-8 lobes to the kidneys, separated by the renal columns, which also provide a framework for vessels that enter and leave the cortex. The pyramids and renal columns combine to make the lobes of the kidneys. The renal hilum is the entry point and exit side of the main blood vessels, nerves, ureters, and lymphatics of the kidneys. These face toward the middle of the body. The renal pelvis also emerges from this structure, which is the point at which the urine first collects before leaving via the ureters. The pelvis has smooth muscle that undergoes peristalsis to propel urine towards the ureter. The renal arteries supply the kidneys, coming from the descending aorta; the renal veins leave the kidneys, emptying into the inferior vena cava. The renal artery is large and first divides into multiple segmental arteries, which branch further to form interlobar arteries (between the lobes). They pass through the renal columns in order to reach the renal cortex. These arteries branch further into arcuate arteries and further branch into cortical radiate arteries and finally into the afferent arterioles. The afferent arterioles are large in number because they need to service about 1.3 million nephrons in each kidney.

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A nephron is the microscopic functional unit of the kidneys. Each will filter the blood and reabsorb much of the filtered water and other constituents, sending only a small amount through the system as urine. Figure 109 shows the basic features of the nephron:

The filtration starts with the glomerulus, which is a tuft of high-pressure capillaries that receives blood from an afferent arteriole and sends blood out of the efferent arteriole. The remainder of the nephron involves a complex tubular system that surrounds the glomerulus—a structure that together is called the Bowman’s capsule. The glomerulus and Bowman’s capsule together make the renal corpuscle. The exiting arteriole, the efferent arteriole, carries the filtered blood. The efferent arteriole goes to a series of peritubular capillaries and the vasa recta (around the tubules). This blood finally exits the kidneys through the renal vein. This complex system (the glomerulus leading to the peritubular capillaries) is basically a capillary bed leading to another capillary bed. This meets the definition of a “portal system,”

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with an arteriole leading to another arteriole between the capillary beds. This is similar to the portal system in the liver, the hypothalamus and pituitary complex. The cortex is lighter in color compared to the remainder of the kidneys. All of the renal corpuscles as well as the proximal and distal convoluted tubules (called the PCTs and DCTs) are found in the cortex. There are cortical nephrons that are defined as small nephrons that have a loop of Henle that doesn’t reach beyond the cortex. Within these are juxtamedullary nephrons that have longer loops of Henle that dip into the deeper regions of the medulla.

MICROSCOPIC KIDNEY ANATOMY The microscopic anatomy of the kidneys involves the anatomy of the nephron. There are three major functions of the nephron: filtration, reabsorption, and secretion. There are minor functions of the nephrons as well, including blood pressure control (through renin secretion), RBC production (through erythropoietin secretion), and calcium absorption (through making calcitriol or active vitamin D). Figure 110 is another, more structural, illustration of the nephron:

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The Bowman’s capsule or glomerular capsule surrounds a renal corpuscle. The glomerulus itself is a high-pressure capillary bed and needs to be high pressure because of the need for proper filtration of blood. The blood is filtered and sends filtrate (basically filtered plasma) to the proximal convoluted tubule. The outer layer of Bowman’s capsule is called the parietal layer and is covered with simple squamous epithelium. The capsule tightly forms a visceral layer that embraces the capillaries. These capsular cells in the visceral layer consisting of podocytes, which have finger-like arms called pedicles that coat the glomerular capillaries and interdigitate to form filtration slits that have gaps forming a type of sieve for filtration. About 10-20 percent of blood plasma filters between the pedicles and are captured by Bowman’s capsule, which funnels blood toward the proximal convoluted tubule (PCT). The only thing separating the capillary lumen and the interior lumen of Bowman’s capsule is a basement membrane. These three structures (the capillary lumen, the lumen of Bowman’s capsule, and the basement membrane) form the “filtration membrane.” This creates pores that are 70 nanometers in diameter that allow plasma to be filtered. The windows of the sieve or fenestrations will prevent RBCs and large proteins from getting through them but most other substances will get through. Most things less than eight nanometers in diameter will easily pass through. The electrical charge will play a role in getting the molecule through the fenestrations. These pores are negatively charged so they will repel things that are negatively charged. On the other hand, positively-charged substances can easily pass through the fenestrations. Globulin proteins cannot pass through the basement membrane so they remain in the blood. There are mesangial cells within the filtration membrane that can contract as a way of regulating the rate of filtration of the glomerulus. Other things that regulate the filtration of plasma include podocytes, which have filtration slits, the negative charge of the pores, the fenestrations in the endothelial cells of the capillaries, and the basement membrane. Together, these cause a filtrate that is devoid of larger proteins and is generally positively charged.

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JUXTAGLOMERULAR APPARATUS There is a juxtaglomerular apparatus or JGA just outside Bowman’s capsule. In addition, there is a part of the distal convoluted tubule (DCT) that comes into direct contact with the place where the afferent and efferent arterioles enter and exit Bowman’s capsule. This place is called the macula densa. This involves cuboidal epithelial cells that monitor the content of ions and other substances in the distal convoluted tubule. The macula densa cuboidal cells adjust their signaling depending on the concentration of sodium in the DCT fluid, releasing paracrine signals. Remember that paracrine signaling involves the secretion of molecules that act relatively locally to signal nearby cells. There is a single cilium in each cuboidal cell of the macula densa that detects the flow rate through the DCT. The paracrine molecular signals given off include ATP and adenosine. The juxtaglomerular apparatus also contains the juxtaglomerular cell. This is a modified, smooth muscle cell surrounding the afferent arteriole. It will contract or relax, depending on the ATP and adenosine concentration released by the macula densa. It regulates the blood flow to the glomerulus. If the sodium concentration is too high, these juxtaglomerular cells will contract to decrease the glomerular filtration rate, resulting in less filtration of plasma and less urine formed. More fluid is retained by the body, which will decrease the blood osmolarity. The macula densa and the juxtaglomerular cells also detect the presence of a low osmolarity in the DCT. If this is the case, the juxtaglomerular cells relax to allow more fluid to flow into the system, which increases the GFR. This will concentrate the blood and cause the osmolarity to rise. This keeps the blood osmolarity roughly the same. The macula densa is also highly important in regulating renin release from the juxtaglomerular cells. Renin is a small protein involved in the vasoconstriction of blood vessels and the raising of blood pressure. Renin takes the protein angiotensinogen to make angiotensin I. This isn’t actually a biologically-active molecule. It needs angiotensin converting enzyme or ACE from the lungs to make angiotensin II, which is the molecule that causes vasoconstriction. Angiotensin II is also responsible for releasing aldosterone by the adrenal cortex. It is this hormone that increases sodium and water reabsorption by the kidneys, further raising blood pressure.

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PROXIMAL CONVOLUTED TUBULE (PCT) After being filtered and collected by Bowman’s capsule, the filtrate enters the PCT. It follows a tortuous path and consists of simple cuboidal cells that have a brush border of microvilli which, as is the case in the GI tract, increase the surface area of the cells so that ions, glucose, and other small solutes can be absorbed and secreted. These are highly active cells that require a lot of ATP and mitochondria in order to actively participate in this process.

LOOP OF HENLE This loop has first a descending and then an ascending part that run parallel to one another, making a sharp turn at the deepest portion. There are thick and thin portions of both aspects of the loop. The thick part has simple cuboidal epithelium, while the thin part has simple squamous epithelium. These have different permeabilities for both water and solutes.

DISTAL CONVOLUTED TUBULE (DCT) This is also a tortuous pathway for urinary filtrate, consisting of simple cuboidal epithelium. These cells have fewer microvilli on their apical surface and need to pump ions against their concentration gradient. There will be a lot of ATP and mitochondria in these cells, which are necessary for the active transport of ions and other molecules.

COLLECTING DUCTS This is where the actual nephron ends. It collects filtrate from several nephrons and slightly modifies it to make urine as a final product. There are actually just 30 terminal ducts from more than a million actual nephrons. Each of these empties into a papilla. They are lined with simple squamous epithelium and have receptors that respond to vasopressin or antidiuretic hormone. When activated, they insert channel proteins called aquaporin channel proteins that allow water out of the collecting duct and into the interstitial fluid. This fluid ends up in the vasa recta in order to hold onto more water if necessary. Without ADH, the urine will be very dilute.

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KIDNEY PHYSIOLOGY One of the more important aspects of kidney function is the GFR or glomerular filtration rate. Roughly five liters of blood get pumped per minute by the heart with about one liter or 20 percent going through the kidneys per minute. Only about 110 milliliters per minute ends up as filtrate. This is referred to as the glomerular filtration rate or GFR. The range is about 80-140 milliliters per minute. This would be a huge amount of urine produced (about 150 to 180 liters per day) if it weren’t concentrated. Fortunately, most of the filtrate gets reabsorbed so only 12 liters of urine are produced per day. There are many things that influence the GFR. The first is the hydrostatic pressure or the pressure of blood against the glomerular capillaries. The second is the hydrostatic pressure of filtrate acting in the opposite direction. The pressure is higher in the capillaries so the net osmosis of water travels from the capillaries to the lumen of the Bowman’s capsule. This is why the capillaries need to be under such high pressure. There is also a colloidal osmotic pressure (the pressure of the non-filtered blood products). This would tend to keep the water in the capillaries and is what the hydrostatic pressure must overcome to filter the plasma. The sum of the influences of hydrostatic pressure and osmotic pressure is called the net filtration pressure or NFP. This is about 10 millimeters of mercury. It is this small amount of pressure that propels a steady amount of water into the filtrate. There is autoregulation of the blood flow reaching the glomerulus so that the amount of pressure influencing the net filtration pressure stays roughly the same. Most of it involves smooth muscle contraction in the afferent capillaries. They contract under high blood pressure situations (to limit kidney blood flow) and relax under low pressure situations (to increase blood flow in the glomerulus). If the mean blood pressure is above 60 mm Hg, there will be adequate GFR. If this is lower than that, the individual is said to be in “shock” and the GFR will drop. The GFR is a tool used to assess the excretory function of the kidneys. If the GFR is down, there is an increase in the potential toxicity of certain drugs. Some drugs must be limited in

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individuals with a low GFR. It is estimated by measuring the creatinine molecule, which is a protein from muscle cell metabolism that is minimally secreted by the nephron.

SECRETION AND REABSORPTION About 180 liters of filtrate get through the glomerulus per day—much of it needing reabsorption back into the bloodstream. As you have learned, this occurs in the PCT, the loop of Henle, DCT, and collecting ducts. Different parts of that system reabsorb and secrete things in various ways. Much of this is passive reabsorption along concentration gradients; however, the reabsorption of water is highly regulated by the kidneys (and the body as a whole). Aldosterone, antidiuretic hormone, and renin (indirectly) will affect the water recovery. Most of water recovery happens in the nephron with only ten percent reaching the collecting ducts. This is where ADH kicks in to recover all, some, or none of the water, depending on how much water is needed by the body. Solutes like glucose, amino acids, oligopeptides, vitamins, and lactate get reabsorbed in the PCT for the most part so they aren’t lost in the urine. Creatinine is secreted in the PCT, while urea is secreted and partially reabsorbed in the PCT (it is later secreted and reabsorbed in other parts of the kidney). Sodium and chloride are mostly reabsorbed throughout the nephron. Bicarbonate is reabsorbed at about 80-90 percent in the PCT, while hydrogen ions are secreted. Potassium can be reabsorbed in the PCT and loop of Henle but is secreted under the regulation of aldosterone in the collecting ducts. Calcium, magnesium, and phosphate are all reabsorbed throughout the nephron. The mechanisms necessary for the reabsorption or secretion of these solutes include diffusion, active transport, facilitated diffusion, osmosis, and secondary active transport. These have already been discussed in previous chapters. Some of these mechanisms need ATP energy, while others are completely passively transported across the cell membranes. The initial filtrate is similar to blood except for the lack of cells and large proteins in the filtrate. There is continual modification after that to make the final urine end product. This modification starts in the PCT. Some substances are secreted in the PCT, while others are reabsorbed. Ultimately these are returned to the circulation by the peritubular and vasa recta capillaries.

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The high pressure of the glomerular capillaries happens because the efferent arterioles are contracted and the afferent arterioles are more relaxed. Sodium is pumped out of the PCT and back into the peritubular capillary—with water necessarily following. This is called obligatory water reabsorption. The PCT is where most of the substances cross back into the bloodstream. Some, such as glucose and amino acids, use symport mechanisms (which is secondary transport) tied to the transportation of sodium. The PCT has simple cuboidal cells that sit against a basement membrane. Substances that cross these cells via a sodium symport mechanism include calcium, chloride, glucose, amino acids, and phosphorus. All of these reabsorption processes ultimately involve ATP energy and the active transport of sodium. About two-thirds of the total amount of sodium, potassium, and water entering the nephron get reabsorbed in the PCT. Other substances, like amino acids, glucose, and vitamins get 100 percent absorbed (unless the glucose level is extremely high). Glucose is bound along with sodium and is transported along with sodium in the PCT. Much of the chloride, calcium, magnesium, and phosphorus get reabsorbed in the PCT. The reabsorption of bicarbonate will be covered more extensively in the chapter on acid-base balance. Its absorption is tied to the acid-base balance in the body, involving an enzyme called carbonic anhydrase. Bicarbonate forms carbonic acid (CO2 and water) in the lumen of the PCT. The CO2 gets transported back through the basement membrane, where it gets enzymatically converted back into bicarbonate ions into the interstitial space outside of the PCT. At the same time, hydrogen ions get secreted into the PCT lumen. As mentioned, there are thick and thin segments of the loop of Henle. They participate in the recovery of more sodium and water in the filtrate. When these are recovered, they enter the vasa recta to get back into the systemic circulation. The thin segments of the loop of Henle have aquaporin channel proteins to allow water to flow unrestricted, accounting for about 15 percent of the water taken up by the nephron. Small amounts of urea, sodium, and other ions are recovered.

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There are more thick parts of the ascending loop than there are in the descending loop. These cells do not have a brush border and do not have aquaporin channel proteins so they do not allow water to get through. Sodium is actively pumped through the cells but water does not get through so the solution becomes more dilute. The urine is fairly dilute in the DCT. Even so, about 10-15 percent of the water is recovered in that part of the nephron. Aldosterone increases the movement of sodium and chloride out of the DCT lumen and into the peritubular capillaries. Parathyroid hormone receptors in the DCT will respond to parathyroid hormone (PTH) and will increase reabsorption of calcium back into the body. The collecting ducts contain principle cells (which help recover sodium and potassium) and intercalated cells (that absorb either hydrogen ions or bicarbonate, depending on the pH of the body). This is also where ADH acts on the cells to retain more water to keep the osmolarity of the blood within homeostatic ranges. As you’ll remember, this is ultimately under the control of the hypothalamus, which will detect the osmolarity of the bloodstream. The principal cells also respond to aldosterone to regulate sodium recovery by the kidneys.

REGULATION OF KIDNEY BLOOD FLOW The regulation of kidney blood flow involves many factors. There is innervation via the celiac plexus and splanchnic nerves that is sympathetic in nature. When there is sympathetic input, there is vasoconstriction of the afferent arterioles that decreases the GFR and renal blood flow in general. This is part of the fight-or-flight response. In addition, sympathetic input will increase renin release in situations of low blood pressure in order to increase the pressure in the glomerulus. There are several autoregulatory mechanisms as well. The first is the myogenic mechanism, in which rising blood pressure will cause relaxation of the arteriolar smooth muscle to maintain a steady flow of blood to the glomerulus. The opposite effect happens in low blood pressure situation. There is also the tubuloglomerular feedback mechanism, involving nitric oxide. This is the activity discussed before regarding the macula densa, which secretes adenosine and ATP,

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affecting the nitric oxide concentration in the glomerular arterioles. Nitric oxide is a vasodilator that will increase the GFR. The renin-angiotensin-aldosterone system has already been discussed. Renin is secreted by the juxtaglomerular apparatus, ultimately causing vasoconstriction and a rise in blood pressure. This will affect the blood pressure in situations of low blood volume or dehydration so that the net effect is to preserve the blood volume and limit fluid loss—by decreasing the GFR. Aldosterone will promote sodium reabsorption by the nephron, retaining water as well and reducing the potassium level in the body. Endothelins are strong vasoconstrictor peptides produced by the renal endothelial cells, cells of the DCT, and mesangial cells in the glomerulus. Angiotensin II, epinephrine, and bradykinin will increase the endothelin release. This isn’t a problem with normal individuals but will cause problems in people with certain types of kidney disease. In addition, endothelins will damage podocytes, reducing the overall glomerular filtration rate or GFR. There are hormones that act in an opposite way to the action of aldosterone, such as natriuretic hormones. These will block aldosterone release, allowing more water to exit via the urine. Atrial natriuretic hormone produced by the atria of the heart in response to being overstretched; this results in the loss of water in the kidneys and lowered blood volume (and blood pressure).

OTHER KIDNEY FUNCTIONS There are other important functions of the kidneys that are apart from the actual filtration of blood and the making of urine. These include the following: •

Elimination of drugs and hormones—the kidneys are responsible for the excretion of many types of water-soluble drugs and hormones. This is true mainly of smaller proteins and molecules.

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Vitamin D Synthesis—as mentioned, vitamin D needs to be activated and made into calcitriol from calcidiol. This makes active vitamin D3 that maintains calcium concentrations in the bloodstream.

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•

Erythropoiesis—the kidneys will sense a low oxygen tension in the bloodstream and will cause erythropoietin (EPO) secretion. People with kidney failure can lose EPO production and will develop anemia from this.

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Blood pressure regulation—this happens mainly through the regulation of water and sodium balance in the kidneys and in the body. A loss of kidney function can lead to a loss of volume control in the kidneys, which can result in low blood or high blood pressure situations.

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Osmolarity regulation— the kidneys must hold on to protein in order to maintain the osmolarity of the blood system. If protein is lost by damaged kidneys, this can lead to a loss of osmolarity and the potential for leakage of water into the interstitial spaces. This leads to peripheral edema.

•

pH Regulation—this involves the maintenance of the pH of the blood and body so as to keep homeostatic mechanisms in place.

URINE COMPOSITION So far, we have learned about the making of urine by the glomeruli and the rest of the renal tissue. While nearly 200 liters of filtrate pass through the glomeruli per day, all but 1-2 liters are made as urine during this time. The urine composition depends on water intake, level of exercise, nutrient intake, environmental temperature, and others. Urine can be fairly clear or dark amber, depending on how concentrated it is. A urinalysis is done to assess the presence or absence of kidney diseases as well as other possible diseases (such as liver disease or diabetes). The color of urine comes mainly from the breakdown of hemoglobin and the production of urochrome, a yellow breakdown pigment. The urine color can also be affected by eating berries, fava beans, or beets, which contain pigmented molecules. Blood in the urine comes from bladder or kidney infections, urinary tract infections or cancers, and sometimes kidney stones. Dehydration will darken the urine and will make it slightly more malodorous. Ammonia comes from the urea in the urine but doesn’t create an odor until the urine has sat outside the

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body for a period of time. Certain foods, like asparagus, fish, garlic, and onions will cause an aromatic urine. The volume of urine depends on the state of hydration of the body. A minimum of 500 milliliters of urine must be created in order to get rid of body waste products. Oliguria involves severe low output of urine, while polyuria involves severe increased output of urine. Anuria involves the absence of urine completely. The pH of the urine varies according to the diet and the pH of the bloodstream, as urine will help regulate the homeostasis of the acid-base situation of the body. The specific gravity of the urine is the measure of the number of solutes in the liquid per unit of volume. This is easier to measure than the osmolarity. Water has a specific gravity of 1.0 and all urine will have a specific gravity greater than that. Normally, cells won’t be present in urine but, in cases of a bladder infection, there will be leukocytes. These cells will release leukocyte esterase, which is also a test that is done on a urine dipstick in order to determine if there are leukocytes in the urine. Protein is not usually found in the urine because it doesn’t pass through the glomerular capillaries. In cases of kidney damage, however, there can be proteinuria or a positive test for protein in the urinalysis. The urine dipstick will also assess urine for ketones, which are byproducts of fatty acid metabolism. This is seen in severe diabetes and in the presence of a low carbohydrate, low protein diet. The nitrite test on a urinalysis is a test done to evaluate the urine for bacteria. When gramnegative bacteria are in the urine, they will metabolize nitrates into nitrites, which will be detected in the urine.

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KEY TAKEAWAYS •

The urine is created by the kidneys, where it is drained by the ureters, stored in the bladder, and exits via the urethra.

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The blood is filtered through the glomerulus, which is encased by Bowman’s capsule.

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About 180 liters of fluid get filtered per day but, because of reabsorption, only 1-2 liters of urine get produced during this time.

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There are controls over the GFR that involve local paracrine function and hormonal (endocrine) function.

•

The kidneys also participate in the making of RBCs, blood volume regulation, pH balance, and vitamin D3 production.

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QUIZ 1. What type of epithelium is lining the inner wall of the ureters? a. Simple squamous b. Transitional c. Stratified squamous d. Simple columnar Answer: b. The transitional epithelium is characteristic of many of the epithelial linings of urinary structures, including the ureters. 2.

What is the approximate upper limit of bladder volume in milliliters? a. 150 milliliters b. 300 milliliters c. 600 milliliters d. 1200 milliliters Answer: c. The approximate upper limit of bladder volume is about 600 milliliters. Above 150 milliliters, there will be an urge to void that can be overcome until the bladder fills to about 300-400 milliliters.

From where does the buffering system for the male sperm come during ejaculation? a. Ejaculatory ducts b. Prostate gland c. Cowper’s glands d. Seminal vesicles Answer: c. The Cowper’s glands secrete mucus and a buffering liquid in order to protect the male sperm from being in such an acidic environment.

Which nerve handles the voluntary control over the external urethral sphincter? a. Pudendal nerve b. Sacral nerve 363

c. Hypogastric nerve d. Pelvic nerve Answer: a. In both males and females, it is the pudendal nerve that innervates and exerts voluntary control over the external urethral sphincter. 5.

What is the kidney structure that receives and exits the blood vessels of the kidney called? a. Calyx b. Papilla c. Medulla d. Hilum Answer: d. The hilum is the structural aspect of the kidneys that receives and exits the main blood vessels serving the structure.

Where does the blood go in the kidney’s nephron after passing through the afferent arteriole? a. Efferent arteriole b. Glomerulus c. Bowman’s capsule d. Vasa recta Answer: b. The glomerulus is a collection of capillaries that receives blood from the afferent arteriole as part of the nephron of the kidney.

There are several things that locally regulate which and how many substances get past the filtration membrane in the glomerulus. Which is not one of these? a. Mesangial cell constriction b. Podocyte fenestrations c. Capillary endothelial fenestrations d. Hydrophobic pores through the filtration membrane

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Answer: d. Each of these play a local factor that plays into getting substances through the filtration membrane except that the pores are negatively charged and are not hydrophobic. 8.

There are cuboidal cells that in the nephron that specifically detect the flow rate and sodium ion concentration of the distal convoluted tubule. What are these cells collectively called? a. Juxtaglomerular apparatus b. Proximal convoluted tubule c. Macula densa d. Bowman’s capsule Answer: c. The macula densa is a collection of ciliated cuboidal cells that detect the flow rate and the sodium ion concentration of the fluid in the distal convoluted tubule, sending out paracrine signals in response.

What is the glomerular filtration rate or GFR? a. The amount of urine produced per day b. The amount of filtrate produced per day c. The amount of plasma filtered per minute d. The amount of urine produced per minute Answer: c. The amount of plasma filtered per minute is considered the glomerular filtration rate. It is on average about 110 milliliters per minute.

10.

Which molecule does not participate in the retaining of water by the kidneys? e. Renin f. Antidiuretic hormone g. Aldosterone h. Epinephrine

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Answer: d. Each of these will directly or indirectly regulate the amount of water getting reabsorbed by urinary filtrate, except for epinephrine, which does not play a major role in this process.

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CHAPTER SIXTEEN: FLUIDS, ELECTROLYTES, AND THE ACID-BASE SYSTEM This chapter includes a discussion of the various fluid compartments in the body and how water and electrolytes are balanced by the somatic cells and by the renal system. Acid-base physiology depends on activities of both the lungs and the kidneys, which are examined in this chapter; there are several acid-base disorders that require compensation by both of these systems—also covered in the last part of the chapter.

FLUID COMPARTMENTS In humans and in other living things, water and “aqueous solutions” are the basis of life. Inside water, which is the solution, are solutes, or the dissolved substances in water. Solutes can be anything from a small ion to a large protein. Charged particles in solution are called ions or electrolytes. Except in localized situation, the positive charge and the negative charge are balanced with positive ions matching a negative ion. As we’ve learned, however, the body uses charged particles to create a net positive or negative charge in many cellular functions. There are semi-permeable membranes in cells with water moving across the membranes via osmosis from regions of high concentration to regions of lower concentrations. These semipermeable membranes otherwise maintain a balance of solutes inside and outside the cell but use pumps and other mechanisms to keep the interior solution in the cell different from the outer solution in the cell. The body is about 50-60 percent water in adults but is up to 75 percent in infancy. This difference is because of changes in the water content of the muscles, fat, bone, and other tissues from infancy to adulthood. The brain and kidneys have the highest water content (at about 80-85 percent) with teeth having the lowest water content at 8-10 percent. There are different fluid compartments in the body, separated by physical barriers. The two main compartments in humans is the intracellular fluid (ICF) compartment and the extracellular fluid (ECF) compartment. Intracellular fluid means “within the cell”, while extracellular fluid 367

means “outside of the cell.” There are two subdivisions of the extracellular fluid: the plasma and the interstitial fluid or IF. The ICF is inside the cell, making up mainly the cytoplasm or cytosol. It accounts for up to 60 percent of the total body water, or about 25 liters of fluid. This tends to be a stable fluid volume because it is highly regulated to keep the solute concentration the same inside the cell. If too little water is seen in the cell, the cell’s cytoplasm is too concentrated for normal cellular activities. If too much water enters the cell, the cell will burst open. The rest of the fluid in the body comes from ECF or extracellular fluid. About 20 percent of the ECF is plasma, while 80 percent is IF or interstitial fluid. Plasma, as you know, is the fluid constituent of blood, while the IF is between the cells. There are other ECF fluids that are not as high in quantity. These include things like the cerebrospinal, lymph, pleural cavity, pericardial, and synovial fluid. The plasma and IF have similar compositions, while the ICF is markedly different. There is a great deal of sodium, bicarbonate ions, chloride, and protein in plasma but the IF is high in just sodium, chloride, and bicarbonate but not protein. The ICF, on the other hand, has high potassium, phosphate, protein, and magnesium concentrations. This happens because of a continual pump that pumps out sodium and pumps in potassium into the cells. As mentioned, the body fluids are mostly neutral in charge. The positively charged ions match with the negatively charged ions. Sodium and chloride are concentrated outside of the cell, while potassium is high inside the cell, mainly because of the sodium-potassium pump, which requires ATP energy to function. Figure 111 shows the sodium-potassium pump within the cell membrane:

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Hydrostatic pressure changes cause movement of fluid between the compartments. The hydrostatic pressure of blood involves the pressure of blood against the walls of the blood vessels by the pumping activity of the heart. This is called the capillary hydrostatic pressure, which opposes the colloid osmotic pressure, or the pressure exerted by the fact that the solutes (mainly albumin) “need” water to stay in solution so it keeps water in the plasma. The filtration pressure squeezes fluid out of the blood into the IF around the cells. This fluid goes into the lymph fluid and reenters via the lymph ducts. Hydrostatic pressure is what makes the capillaries in the nephrons filter the blood to make urine. This is the most important thing that controls this filtration process. This must oppose the hydrostatic pressure on the other side of the filtration membrane and the colloidal osmotic pressure of the albumin in the plasma. If there is dehydration, the hydrostatic pressure drops and the kidney function is impaired, with fewer wastes getting filtered and kidney failure. Fluid moves across an osmotic gradient between the different fluid compartments. Osmotic gradients happen because there is a difference in concentration of the solutes from one side of the membrane to the other. Water will move through osmosis from a high-water content (low 369

solute concentration) to a low water content (high solute concentration). As conditions change in the body (which happens all the time) so will the flow of water. By contrast, the movement of solutes is active and involves the usage of ATP energy and what we now know involves active transport. Active transport allows cells to move a substance against a concentration gradient, meaning from an area of low concentration to an area of high concentration. This is what the sodium-potassium pump is designed to do because both sodium and potassium go from low to high concentrations across the cell membrane. Things like lipids and gases can diffuse easily and passively across the membrane, while the movement of water is basically passive because of aquaporins that allow water to pass through. Other molecules, particularly hydrophilic molecules (such as amino acids, ions, and glucose), do not have the ability to get passively through the cell membrane and need facilitated transport, active transport, or secondary active transport (using other molecules to allow their passage through the membrane).

WATER AND ELECTROLYTE BALANCE The average water intake is about 2.5 liters per day. The majority is ingested through the diet; about 230 milliliters is generated internally through the metabolic processes, such as aerobic respiration. About the same amount exits the body through different routes, such as through stool, urine, the respiratory tract, and skin (with the most exiting through urine). The kidneys have the ability to adjust their output in order to maintain a proper fluid balance in the body. Insensible losses include those from the skin and respiratory tract, with skin losses happening even when a person does not sweat. The osmolality is the ratio of solutes in a particular solution to the volume of solvent. This applies to plasma osmolality, which involves the protein and ions in the solution. The osmolality differs depending on whether the person is overhydrated, normally hydrated, or dehydrated. Fortunately, the plasma osmolality is tightly controlled through regulating the input and output of water.

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Water intake is controlled by drinking fluids. In dehydration, there is a net loss of water that results in low water content in the tissues and blood. As the blood becomes more concentrated, the thirst response is triggered. There are osmoreceptors in the hypothalamus (in the thirst center) that will trigger a conscious awareness of thirst. Dehydrated individuals will have ADH (antidiuretic hormone) released by the hypothalamus for water to be recovered by the kidneys, which helps dilute the plasma. Sympathetic signals also cause decreased output of the salivary glands and a dry mouth, which increases the sensation of thirst. There are also baroreceptors in the aorta and carotid arteries in the neck that detect blood pressure decreases that come from a low blood volume. This will increase the heart rate and contractility of the heart in order to compensate for low blood pressure detected in these areas. The renin-angiotensin system causes changes in the blood pressure as well. The end result is the formation of angiotensin II, which also stimulates thirst and the release of aldosterone from the adrenal glands. Aldosterone is the sodium reuptake hormone; however, since water follows sodium, water is reabsorbed as well so the blood volume increases. If there isn’t enough fluid taken in, there will be dehydration. The same thing happens in vomiting and diarrhea. It also happens in people who are athletes and sweat more fluid than they can take in. The problem can lead to low blood pressure, loss of consciousness, and possible death, particularly if the dehydration is sudden and not compensated for. As mentioned, most water loss comes from loss in the kidneys. About 1.5 liters of urine is produced per day, depending on the person’s hydration levels with a minimum necessary of 500 milliliters to remove toxic substances in the body. If there is too much water taken in, diuresis occurs, which involves an excess of urination that starts about 30 minutes after drinking large amounts of fluid—peaking at one hour after fluid ingestion.

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ANTIDIURETIC HORMONE (ADH) This is also known as vasopressin, and controls the amount of water reabsorbed in the collecting ducts and, to some extent, in the tubules of the kidneys. It is produced by the hypothalamus but is released by the posterior pituitary gland in response to osmoreceptors in the hypothalamus that detects a high osmolality in blood plasma. The ADH will constrict peripheral circulation to increase the core blood supply. It will also cause the aquaporin proteins to be inserted into the cell membrane to allow more water uptake in the kidney cells. As the blood plasma becomes less concentrated, the aquaporins are removed from the cell membrane so that water remains in the collecting ducts for urination.

ELECTROLYTE BALANCE Electrolytes are electrically-charged ions in the fluid of all body compartments. They assist in maintaining an electrical potential across a cell membrane, in the formation of action potentials in nerves, and in muscle contraction. Ions also help stabilize enzymes and proteins, aid in hormone release, and contribute to the osmotic balance inside and outside of the cells. There are many electrolytes but the most important ones in humans are sodium, potassium, bicarbonate, calcium, phosphate, iron, zinc, copper, magnesium, chromium, molybdenum, and manganese. Some of these are found in the largest concentrations and play a bigger role in body functioning, such as sodium, potassium, chloride, calcium, bicarbonate, and phosphate. The six major ions have many functions. For example, calcium and phosphate go mainly to the bones and teeth but are used in other functions as well—with the bones and teeth as reservoirs for these ions in the body. The goal is to keep the concentration of these ions stable in and out of the cells. Other ions are important in maintaining the osmolality of cells and ECF. Ion excretion comes via the kidneys primarily but, in some cases, there is loss via the sweat and stools. Sodium and chloride are lost in sweat, while bicarbonate and chloride can be lost in vomiting and diarrhea. While sodium, potassium, and chloride concentrations in urine can be simply assessed in a urinalysis, the calcium and phosphate levels in urine need to be assessed

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via a 24-hour urine collection sampling. Bicarbonate is the only major ion not excreted in urine to any extent but is used in buffering of plasma. Sodium is the major cation in the ECF. It is responsible for 50 percent of the osmotic pressure gradient between the ECF and the ICF. About 1-2 millimoles of sodium are required per day; however, more than 130 millimoles per day are taken in by the average American individual. This contributes to the high frequency of hypertension in this population. It is excreted by the kidneys after being filtered via the glomerular capillaries. Most, however, is reabsorbed in the PCT. Hyponatremia is a low concentration of sodium, usually because of an excess of water that dilutes the ion concentration but can be from diuretic use, sweating, vomiting, or diarrhea. Diabetes can cause polyuria (or excessive urination) and acidosis, which can lower the sodium level. Congestive heart failure will cause hyponatremia as well from an excess of water in the system. Hypernatremia can come from water loss, ADH, and aldosterone imbalances. Potassium is the major intracellular cation. It helps establish the resting membrane potential by flowing into the cells after depolarization of the neuron and muscle cells. Its concentration is low, however, compared to sodium, so it doesn’t contribute to osmotic pressure. The recommended daily intake of potassium is 4700 milligrams. Potassium is excreted via the renal tubules and collecting ducts. It participates in the ionic exchange with sodium in the tubules of the kidneys because of aldosterone, which activates the sodium-potassium pumps. Low potassium is called hypokalemia and can be caused by low potassium intake, vomiting, diarrhea, and alkalosis. Hyperkalemia involves an elevation of potassium, which can be caused by an increased potassium intake or from kidney failure. Too much potassium in the ECF can partially depolarize the neuronal and cardiac cells, causing a lack of relaxation of the heart muscle, seizing the heart and stopping blood pumping. This can be fatal. Chloride is the main extracellular anion. It contributes to the osmotic pressure gradient between the ICF and ECF, maintaining adequate hydration. It balances the cations in the ECF in order to maintain an electrically neutral environment. Its reabsorption in the kidneys directly follows the sodium ions. Low chloride levels happen when there is a defect in renal tubular

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absorption or with metabolic acidosis, vomiting, or diarrhea. High chloride levels happen with dehydration, excessive salt intake, salicylate poisoning, congestive heart failure, and cystic fibrosis. Bicarbonate is the second most common ion seen in the bloodstream. It is responsible mainly for acid-base balance as part of a buffer system. Because only a small amount of CO2 gas can be dissolved in the fluids of the body, more than ninety percent of this is converted into bicarbonate with the help of water. This is because CO2 and water combine to make carbonic acid, which breaks into bicarbonate and a hydrogen ion. Once the bicarbonate gets to the lungs, the reverse reaction occurs and CO2 is both produced and exhaled. Calcium is found in a high concentration in the body but it is mainly stored in bones, making up about two pounds of the total body weight. It is also a major component of teeth. It is found in the bloodstream, although 50 percent is found bound to proteins. It is essential for the activity of enzymes, for muscle contraction, hormone and neurotransmitter function, and for the coagulation of blood. Low calcium levels are seen if there is hypoparathyroidism, while high calcium levels are seen in hyperparathyroidism and certain types of cancer. Phosphate is found in three separate ionic forms and switches back between these forms. It is found mainly in bone as calcium-phosphate salts in the bones and teeth. It is an important component of the cell membrane, found as phospholipids, and is in important molecules, such as nucleotides and ATP. Finally, it acts as a buffer system in the body. Hypophosphatemia (low phosphate levels) can be seen in alcohol withdrawal, malnourishment, and antacid use. High levels of phosphorus are seen if there is poor renal function or with certain types of leukemia. It is seen in greater concentrations in the ICF versus the ECF. Sodium and potassium are regulated together. As sodium is taken up by the renal collecting ducts, potassium is excreted. This exchange of ions happens through the action of aldosterone and angiotensin II. Aldosterone, as you remember, takes up sodium and water, while it lets go of potassium at the same time. Angiotensin II causes vasoconstriction and increases the GFR as a result. It also signals aldosterone release.

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Calcium and phosphorus are co-regulated as well in the body. It involves three major hormones: Parathyroid hormone (PTH), vitamin D3 (calcitriol), and calcitonin. They are released in varying amounts in response to the calcium levels in the body, with phosphate following it. PTH will bring up calcium levels and calcitonin will lower the calcium levels. Calcitriol will increase the calcium levels through increased absorption.

ACID BASE PHYSIOLOGY Acid-base balance in the body depends on the pH level. The pH level of a solution is the measure of the hydrogen ion and hydroxyl ions in the system or the balance of acids and bases. The pH scale runs from 1 to 14, with a low pH being acidic and a high pH being alkaline or basic. The pH of the body is slightly above 7, making it very nearly neutral when it comes to acid-base balance. To keep the body from fluctuating greatly in pH levels, there are buffering systems that keep this from happening. A buffer or “buffering system” represents either a week acid or a weak base that will take up hydrogen ions or hydroxyl ions to protect the system. There are several buffering systems in place, both inside and outside the cells, which maintain the pH of the system within a narrow range. It takes just seconds for these buffering systems to take place so that the blood pH is maintained. An example of this is the change in respiratory rate that can increase or decrease the CO2 level, which is a major part of the buffering of the bloodstream. The three major buffering systems in the body are: the bicarbonate/carbonic acid system, the phosphate system, and protein buffers. Within the cells, proteins are the major buffers; however, in the bloodstream, it is mainly the bicarbonate/carbonic acid system. Protein buffers are common in living systems. Proteins have both positively-charged amino groups as well as negatively-charged carboxyl groups. This combination of positive and negative charges adds to a buffer system, binding hydrogen and hydroxyl ions, depending on the end being looked at. Protein buffering systems make up two-thirds of the buffering that takes place in the bloodstream and almost all of the buffering that takes place within the cells.

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Hemoglobin acts as a buffer inside the RBCs. When CO2 goes into bicarbonate within the cells, there are hydrogen ions made as part of this that could greatly affect the pH if it weren’t for the buffering power of the hemoglobin molecule. Hemoglobin will take up the hydrogen ion, reducing itself, and dissociating oxygen. The pH within the cells is maintained. The reverse of this process happens in the lungs, where CO2 gas is made and exhaled, water is created out of this, and oxygen binds to the hemoglobin protein. Phosphate buffers involve the weak acid (sodium dihydrogen phosphate) and the weak base (sodium monohydrogen phosphate). These will flip back and forth, taking up hydrogen ions or hydroxyl ions in order to maintain the pH of the bloodstream. Bicarbonate is a major buffer in the bloodstream. It is regulated by sodium, which is also the case with the phosphate buffering system. Sodium bicarbonate is a weak base, while carbonic acid is a weak acid. There is a ratio of bicarbonate ions to carbonic acid in the bloodstream that is about 20:1 to keep the pH within the normal range. What this means is that, as a system, it protects better against an acid environment than it does an alkaline environment, which is a good thing because most metabolic wastes are acidic in nature. The carbonic acid level is most closely associated with the CO2 level in the bloodstream. Throughout the lung tissue, carbonic acid is dissociated through the action of carbonic anhydrase to make CO2 and water. The level of bicarbonate in the bloodstream is controlled by the kidneys, while the level of CO2 is controlled by the lungs. Bicarbonate is a significant buffer as a weak base in the interstitial fluid in the tissues of the body.

THE LUNGS AND ACID-BASE BALANCE The lungs participate in acid-base balance to a significant degree by regulating the amount of carbonic acid in the bloodstream. The levels of CO2 and carbonic acid go together so as the CO2 level increases, so does the carbonic acid level. The exhalation of CO2 results in a loss of carbonic acid concentration and raises the pH; the holding onto CO2 results in a gain of carbonic acid concentration and lowers the pH level. This can happen really quickly and is the

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first response to changes in pH. This means that hyperventilation raises pH and hypoventilation lowers the pH. When exercising, there is more lactic acid made and more CO2 made as part of the metabolic processes that happen in the exercising body. This would normally lead to acidosis and a lowering of the pH of the body; however, the respiratory rate and depth goes up in order to remove CO2 and to balance the acid-base status of the body. There are chemoreceptors in the aorta and carotid sinuses that will adjust the respiratory rate to balance the CO2 level. The same thing happens with pH detection in the medulla that will cause the respiratory centers to affect the respiratory rate.

THE KIDNEYS AND ACID-BASE BALANCE The kidneys play an important role in acid-base balance but compensation takes place more slowly than with the lungs. The kidneys control the amount of bicarbonate in the bloodstream, which is a weak base. The blood bicarbonate level will be too low in chronic adrenal insufficiency/Addison’s disease (low aldosterone levels), severe diarrhea, and the use of certain diuretics. Kidney damage will also reduce the bicarbonate levels as can high ketone body levels (as in diabetic ketoacidosis). The ketone bodies will bind to bicarbonate in the urine filtrate so it cannot be reabsorbed in the tubules. The cells of the tubules in the kidneys cannot absorb bicarbonate at all, so a system is in place to take this back up by the tubular cells. It is dependent on the exchange of sodium for hydrogen ions in the renal tubules. Bicarbonate combines with hydrogen and CO2 is made along with water and CO2 diffuses across the tubule back into the kidney interstitial tissues. The reverse reaction occurs in the tissues so that bicarbonate can be taken in by the peritubular capillaries. Hydrogen will be re-secreted back into the tubules. Sometimes, the hydrogen ions are unavailable for bicarbonate in the filtrate. This happens when phosphates, sulfates, and ammonia are in the filtrate. They will capture hydrogen ions so that bicarbonate cannot be taken back up into the renal interstitial tissues. If too much

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potassium is in the system, there will be fewer hydrogen ions in the filtrate and less conservation of bicarbonate.

ACID-BASE DISORDERS The normal pH in the blood is between 7.35 to 7.45. Levels below this are considered to be acidotic, while levels above this are considered to be alkalotic. The symptoms of acidosis are fatigue, lethargy, headache, and confusion. The symptoms of alkalosis are cognitive impairment, numbness and tingling, muscle twitching, and nausea/vomiting. Metabolic and respiratory disorders can cause either acidosis or alkalosis. The respiratory component involves CO2, which parallels the carbonic acid level, while the renal component involves bicarbonate levels. Metabolic acidosis involves primary bicarbonate deficiency. The most common cause of this problem is excessive numbers of organic acids or ketones in the bloodstream. Other causes of metabolic acidosis include diarrhea (with loss of bicarbonate), kidney disease, diabetic ketoacidosis (from ketones), strenuous exercise, methanol toxicity, paraldehyde toxicity, isopropanol toxicity, ethylene glycol toxicity, and salicylate poisoning (from aspirin overdoses). Metabolic alkalosis is from primary bicarbonate excess. This can be caused by ingestion of certain antacids, excess ACTH production in Cushing’s disease, vomiting (loss of acid), and excessive diuretic or laxative abuse. Respiratory acidosis comes from respiratory failure, pneumonia, or congestive heart failure. On the other hand, respiratory alkalosis comes from hyperventilation, salicylate toxicity (after an initial acidosis), and catecholamine excesses. These things rarely happen as “pure diseases” but are rapidly compensated for in the body. The goal of compensatory mechanisms is to maintain the pH of the blood, which is paramount over the actual concentrations of CO2, carbonic acid, and bicarbonate. The lungs will compensate for metabolic acidosis by blowing off CO2 and will compensate for metabolic alkalosis by holding onto CO2 (within limits, because respiration must to a degree continue to happen or the person will die). 378

The kidneys will eventually compensate for respiratory acidosis or respiratory alkalosis but it takes hours to days for this to occur. Hydrogen ions can be secreted and bicarbonate can be conserved, depending on the pH of the body. This will work to some degree in both elevated and low pH changes in the body.

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KEY TAKEAWAYS •

There are different fluid compartments, including the intracellular space, the plasma space, and the interstitial fluid space.

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There are six major ions involved in controlling the osmotic pressure of the blood and intracellular fluids; some will participate in action-potential changes and other cellular processes.

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Buffering systems involve weak acids and weak bases that maintain a steady pH of the systems they buffer.

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The lungs and kidneys both participate in the acid-base physiology of the body.

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There are several acid-base disorders that can involve metabolic or respiratory acidosis or alkalosis.

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There are compensatory mechanisms that act to maintain the pH of the blood within the very narrow range of 7.35-7.45.

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QUIZ 1. Which body tissue contains the highest concentration of water? a. Bones b. Muscle c. Brain d. Adipose tissue Answer: c. The brain is about 80-85 percent water, making it the highest in water concentration of the above listed body tissues. 2.

Which fluid compartment has the most fluid/water in it? a. ICF b. ECF c. Interstitial fluid d. Plasma Answer: a. The ICF or intracellular fluid volume is the greatest, making up about 60 percent of the total body water.

What is the driving force that causes the filtration of fluid from the renal capillaries in the glomerulus? a. Colloidal pressure in the capillaries b. Hydrostatic pressure in Bowman’s capsule c. Colloidal pressure in Bowman’s capsule d. Hydrostatic pressure in the capillaries Answer: d. The driving force that causes filtration of fluid from the renal capillaries across the filtration membrane is the hydrostatic pressure in the capillaries, which is higher in these capillaries versus most other capillaries.

Which molecule type is not passively transported through the cell membranes? a. Glucose 381

b. CO2 c. Lipid d. Water Answer: a. Water has aquaporins to allow it to passively travel into the cell, while gases and lipids have the ability to passively diffuse across the membrane. Glucose requires facilitated transport in order to get through the hydrophobic membrane. 5.

There is a minimum amount of water that must be excreted through the kidneys per day in order to get rid of metabolic waste products. What is this minimum amount? a. 150 milliliters b. 500 milliliters c. 800 milliliters d. 1.2 liters Answer: b. A minimum of 500 milliliters of fluid through urine is necessary to get rid of the normal metabolic wastes in the body. Anything lower than this will not result in adequate waste excretion by the kidneys.

Which ion is least excreted in the urine by the kidneys? a. Bicarbonate b. Sodium c. Potassium d. Phosphate Answer: a. Each of these major ions is excreted by the kidneys except for bicarbonate, which is hung onto in order to maintain the pH of the plasma and other body fluids.

What is the major extracellular anion? a. Chloride b. Bicarbonate

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c. Phosphate d. Nitrate Answer: a. Chloride naturally follows sodium and is the most common extracellular anion. 8.

Which major ion is one that primarily participates most in acid-base balance? a. Potassium b. Sodium c. Bicarbonate d. Chloride Answer: c. Bicarbonate is the major ion responsible for acid-base balance within the body as it involves carbonic acid and carbon dioxide balance.

What does hemoglobin take up in order to become a buffer to the red blood cells in the tissues? a. Hydrogen ions b. Hydroxyl ions c. Oxygen d. CO2 Answer: a. Hemoglobin will act as a buffer to the biochemical reaction that turns CO2 into bicarbonate and hydrogen ions. The hydrogen ions get taken up by the hemoglobin molecule in order to buffer the system.

10.

What is something not done when a person hyperventilates? a. The pH of the blood will increase. b. The carbonic acid level decreases. c. The CO2 level decreases. d. The bicarbonate level increases.

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Answer: d. Each of these things will happen as a result of hyperventilation but it does not readily affect the bicarbonate level until the kidneys participate in acidbase exchange.

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CHAPTER SEVENTEEN: MALE REPRODUCTIVE SYSTEM This chapter discusses the anatomy of the male reproductive system as well as the physiology, including the male reproductive hormones involved in this system. Finally, the embryological development of the male reproductive system is discussed.

MALE REPRODUCTIVE ANATOMY The major function of the male reproductive system is to produce sperm, the male gamete, containing half of the normal chromosomes in the human body at 23 unpaired chromosomes. The goal of the reproductive system in males is to not only produce these gametes but to facilitate a way for these sex cells to get to the female reproductive tract. This involves the coordinated efforts of the male testes, duct system, endocrine system, and penis.

THE SCROTUM The scrotum is the skin covering over the testes. It is pigmented to a greater degree than is surrounding skin and is muscular, allowing for the reflexive contraction under certain conditions. The purpose of the scrotum is to keep the temperature of the testicles lower than the body temperature by 2-4 degrees Celsius. The subcutaneous muscle layer of the scrotum is called the dartos muscle. It forms a septum that divides the scrotum into two halves, one for each testis. There are two cremaster muscles that come down off the internal oblique muscle of the abdominal wall that covers each testis. The dartos and cremaster muscles can contract in cold weather situations or in cold water so the scrotum can hold the testes closer to the body. These will contract around the scrotum, wrinkling it, and decreasing its surface area in order to retain heat. The opposite happens when the body is exposed to heat or hot environments. The cremasteric reflex involves the contraction on the same side of the body when the upper inner thigh is stroked. This causes an involuntary short reflex in which the contraction of the

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cremaster muscle draws the testis up to the abdomen. The nerves involved are both sensory and motor in nature, involving both the ilioinguinal nerve (sensory) and the genitofemoral nerve (motor).

TESTES The testes are the male reproductive organs, producing both sperm cells and androgenic hormones, mainly testosterone. Unlike the female reproductive system, the testes function throughout the man’s lifespan. These are oval-shaped structures that are each 4-5 centimeters in length. Figure 112 illustrates what the testes look like:

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There are several layers of connective tissue covering the testes. The first is the tunica vaginalis, which has an outer parietal and an inner visceral layer. The second is the tunica albuginea, which is white in color and is the tough layer over the testis itself. It invaginates within the testis to form multiple septa that separate the testis into up to 400 lobules. Sperm cells develop within the lobules in what are called the seminiferous tubules. The seminiferous tubules are tightly coiled tubes that form the main portion of the testis. These are where the sperm cells develop, first as cells that line the seminiferous tubules. The center of each tubule is hollow and is where the sperm cells are released. These sperm cells then enter the straight tubules called tubuli recti and then into the rete testes, which is a fine network of small tubules. There are 15-20 efferent ductules that cross the tunica albuginea and exit the testis itself. The seminiferous tubules are complex, consisting of six different cell types. There are supporting cells known as sustentacular cells and five different types of germ cells. Germ cell development starts at the basement membrane of the seminiferous tubules and progresses toward the inner lumen of the tubule. The cells surrounding the developing sperm cells are called Sertoli cells, also referred to as sustentacular cells. These secrete molecules that promote sperm cell production. They control the life of the germ cell and extend around each germ cell from the basement membrane to the lumen of the seminiferous tubules. There are tight junctions around these sustentacular/Sertoli cells to create a blood/testes barrier. This keeps bloodborne substances from getting to the germ cells and keeps away an autoimmune response from the human immune system. Figure 113 shows the way germ cells develop in the seminiferous tubules:

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The germ cell of the male gamete is called the “spermatogonium” or plural “spermatogonia.” These line the basement membrane inside the tubule and act as stem cells, which can differentiate into a variety of other cells. They divide into primary spermatocytes, secondary spermatocytes, and spermatids, which finally produce mature sperm. This entire process of sperm production is known as spermatogenesis. Spermatogenesis begins at puberty and lasts the duration of a man’s lifetime. Each production cycle starts every sixteen days and lasts about 64 days. The timing isn’t synchronous so there are new cells developing all the time. Sperm counts tend to decline with smoking and after thirty-five years of age but a man is capable of fathering a child throughout his lifespan. The spermatogonium is a diploid cell, meaning it has 46 chromosomes or two pairs of 23 chromosomes each. The end result, however, is the presence of a haploid cell containing just 23 total chromosomes. This means that meiosis must occur, leading to half of the total number of chromosomes. When the spermatogonia undergo mitosis, this leads to another spermatogonium plus one primary spermatocyte. This is the next stage of spermatogenesis. Each cell has identical chromosomes as would be the case in normal mitosis. The same thing happens again when the primary spermatocyte divides to make two secondary spermatocytes. This leads to three identical cells—only two of which go on to make sperm cells (one is still a spermatogonium).

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The secondary spermatocyte undergoes more division that doesn’t involve true mitosis. Instead it undergoes meiosis, in which a total of four cells are made that have half the total number of chromosomes as an adult cell. These are called spermatids. Spermatids are round and have a round, central nucleus with a lot of cytoplasm. These get transformed through the process of spermiogenesis to become spermatozoa or formed sperm, which happens near the lumen of the seminiferous tubules. The sperm get released into the lumen and travel through the ducts just mentioned toward the epididymis.

STRUCTURE OF FORMED SPERM The process of spermiogenesis involves several things. The nucleus is maintained but the cytoplasm is, for the most part, lost. Many organelles are lost and a tail is produced. The cell becomes ovoid in shape. The volume becomes 85,000 times smaller than the female egg. Up to 300 sperm are made each day by one male. Figure 114 outlines what happens in spermiogenesis:

The sperm cell has an acrosome, which is a cap containing lysosomal enzymes, which aids in fertilization of the egg. There are mitochondria that are responsible for powering the flagellum of the sperm cell but no mitochondria in the cell itself. The flagellum consists of an axial filament and a centriole that participates in cell movement. 389

SPERM MATURATION To fertilize an egg, the sperm must be transported from the seminiferous tubules to the epididymis and finally to the penis during ejaculation. The epididymis is a coiled tubular structure that is attached to the testis. It is the main place for sperm maturation. Its total length is about 20 feet long—so long that it takes 12 days for sperm to move through its coils. Smooth muscle lining the epididymal cells will propel the sperm down the tubes. As they mature, the sperm gain their ability to move independently. The end of the epididymis is where mature sperm are held prior to ejaculation.

DUCT SYSTEM Mature sperm must pass through a duct system in order to be ejaculated. There are smooth muscles that propel sperm through the vas deferens or ductus deferens. It is connected with other spermatic cord structures, including connective tissue, arteries, veins, and nerves. It is this structure that will be accessible for a vasectomy, which cuts the vas deferens as it exits the epididymis. The vas deferens extends upward out of the epididymis and through the inguinal canal in the abdominal wall. It enters the pelvic cavity, dilates into a region called the ampulla behind the bladder and then comes back to have the seminal fluid added to it. Figure 115 shows the route of exit of the sperm:

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The semen is the sperm cells plus seminal fluid. In actuality, the sperm cell makes up just five percent of semen; the rest comes from three accessory glands: the prostate, seminal vesicles, and bulbourethral glands. The seminal vesicles make up about 60 percent of semen volume. The main thing that seminal vesicles do is to make fructose, which is the thing that the mitochondria in the sperm cell use to propel the sperm as it goes to make ATP. This is different from normal cells that use mainly glucose for cellular fuel. This fluid then travels to the ejaculatory duct, which is the combined duct made by the ductus deferens and the seminal vesicle duct. These are paired structures that transport seminal fluid into the prostate gland. The prostate gland is just in front of the rectum and beneath the bladder. This surrounds the prostatic urethra and is about the size of a walnut. It secretes an alkaline fluid that will coagulate after ejaculation. This transient thickening of the semen keeps it within the female reproductive tract after ejaculation, which also allows sperm to utilize the fructose for sperm motility.

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The prostate undergoes two periods of growth. It doubles its size at the time of puberty, while after 25 years of age, the prostate enlarges again. Should it enlarge so much that it constricts the outflow of the urethra, it is called benign prostatic hypertrophy or BPH. By the age of sixty, 40 percent of men will have some degree of BPH. This number reaches 80 percent by the age of 60 years. This can be treated medically or surgically so that urine outflow is protected. The bulbourethral glands are paired glands that are also referred to as the Cowper’s glands. They secrete a thick lubricating fluid in the ejaculate that helps lubricate the urethra for sperm to pass. This fluid is released at the time of sexual arousal, just before ejaculate is released. It is the salty part of semen. The penis is the male organ responsible for sexual intercourse or copulation. It is normally flaccid, even during urination but becomes turgid (filled with blood) during sexual arousal. When erect, it allows the organ to penetrate the female vagina in order to deposit ejaculate or semen within the female reproductive tract. The shaft of the penis surrounds the male urethra. It is an erectile structure because of three column-like chambers of erectile tissue that spans the length of the shaft. There are the paired lateral chambers, called the corpus cavernosa (singular is corpus cavernosum). These make up most of the penis. The smaller corpus spongiosum also fills with blood and surrounds the penile urethra. Figure 116 shows the cross section of the male penis:

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The end of the penis is called the glans penis, which is highly innervated and very sensitive, influencing the ejaculation process. The prepuce is the same thing as the foreskin, which is also sensitive and secretes a lubricant that protects the skin of the glans penis. In the circumcision process, this foreskin is surgically removed. This is not done for medical reasons, rather personal or religious reasons, usually within days of a child’s birth. Penile erections happen because of the engorgement of the corpus cavernosa and corpus cavernosum of the penis so the penis can become erect. Nitric oxide is released during sexual arousal from nerve endings near the blood vessels in these structures. This causes relaxation of smooth muscle in the penile arteries, so that they dilate. This increases the blood flow to the penis, causing nitric oxide to be secreted even further by the arterial endothelial cells, furthering the erectile process. This causes the collapse of the veins so that the blood cannot leave the penis, so the erection persists until after ejaculation.

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MALE REPRODUCTIVE PHYSIOLOGY Testosterone is produced by the Leydig cells in the testicles or testes. These are also called interstitial cells because of their location between the seminiferous tubules in the testes. It is secreted as early as the seventh week of development, peaking in the second trimester and allowing for the anatomic differentiation of male sexual organs. The testosterone level increases again at the time for puberty, which causes the secondary sexual characteristics and results in spermatogenesis. The Leydig cells produce 6-7 milligrams of testosterone per day in order to maintain functioning of the male reproductive system. The concentration of testosterone is 100 times greater in the testes than it is in the rest of the male circulation. This will promote spermatogenesis on a regular basis and is necessary to maintain male fertility. It also participates in libido, the development of secondary sexual characteristics, and male muscular development. The adrenal glands also make small amounts of testosterone. Testosterone is regulated in the male reproductive system by the hypothalamus-pituitary-testis pathway. In this system, the hypothalamus secretes gonadotropin releasing hormone, which causes the release of FSH and LH by the anterior pituitary gland. LH or luteinizing hormone stimulates the release of testosterone by the Leydig cells, while FSH or follicle stimulating hormone causes Sertoli cells to become activated to make sperm cells. FSH will also cause the Sertoli cell to release inhibins, particularly inhibin B. These will feed back onto the hypothalamus to cause a reduction in gonadotropin releasing hormone or GnRH. Low testosterone levels will stimulate GnRH in the hypothalamus and high testosterone levels will also feed back onto the hypothalamus. Both of these are negative feedback molecules that allows for adequate control over the Sertoli cells and the Leydig cells.

MALE REPRODUCTIVE DEVELOPMENT The primordial gonads develop very early in embryonic development—about a month after conception, continuing throughout the first and second trimester but stopping development

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after the infant’s birth until the time of puberty. Interestingly, all embryos will become developmentally female unless prompted by male hormones. There needs to be input by the male hormones produced by the Y chromosome in order to cause an embryonic male. There is a gene on the male Y chromosome called SRY found only in males. Without this functioning gene, the fetus will become phenotypically female. The tissue that develops into the gonads are considered bipotential—in that they can become either male or female reproductive organs. The SRY gene causes the recruitment of other genes and the suppression of all female genes. This causes germ cells to become spermatogonia. If this doesn’t happen properly, egg cells or oogonia are formed as they would in the female ovary. Leydig cells in the embryonic testes will secrete testosterone that furthers the development of male sexual characteristics, causing the glans clitoris to become the glans penis instead. The female reproductive duct is called the Mullerian duct, which is suppressed and degraded by secretions in the sustentacular cells, which stimulates the Wolffian duct to develop into the male epididymis, ductus deferens, and seminal vesicles.

PUBERTY Puberty is the stage where primary sexual characteristics develop further along with secondary sexual characteristics. The process starts with GnRH that causes the release of LH and FSH in the anterior pituitary gland. In males, this stimulates spermatogenesis and the Leydig cell’s release of testosterone, leading to the development of secondary sexual characteristics. LH becomes detectable around 8-9 years of age. There is a reduction in the sensitivity of the hypothalamus and pituitary gland to negative feedback so they put out more LH and FSH, even when there are high concentrations of testosterone. Signs of puberty include the following in males: •

Increased size of the larynx, which deepens the voice

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Increased muscular development

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Growth of pubic hair, axillary hair, and body/facial hair

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Testicular growth is the first sign of male puberty. This is associated with an increase in pigmentation of the scrotum and growth of the penis. Facial hair and body hair happen next, followed by deepening of the voice through lengthening of the larynx. The first fertile ejaculations begin at around fifteen years of age with a growth spurt happening toward the end of puberty at a rate of up to four inches per year. Development of puberty can, in some males, continue up until the early 20s.

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KEY TAKEAWAYS •

The male reproductive organs include the testes, scrotum, penis, ejaculatory ducts, and several reproductive glands.

•

Spermatogenesis involves the development of spermatogonia into mature sperm cells that have motility in the seminiferous tubules.

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The seminal vesicles, Cowper’s glands (bulbourethral glands), and prostate gland have secretions that add to the total ejaculate in the male reproductive system.

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Testosterone is the major male hormone, produced by the Leydig cells under a negative feedback loop with the hypothalamus and pituitary gland.

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QUIZ 1. What is the major function of the scrotum in males? a. To make the testosterone for sperm maturation b. To contract in order to have sperm released c. To produce seminal fluid d. To keep the sperm temperature low Answer: d. The scrotum exists to house the sperm-making testes in an environment that is below the normal body temperature because this lower temperature is required for sperm growth and maturation. 2.

The cremasteric reflex involves what part of the male reproductive system? a. Epididymis b. Scrotum c. Penis d. Prostate gland Answer: b. The cremasteric reflex is a short sacral reflex involving the contraction of the scrotum when the upper medial thigh is stroked.

What is the major function of the male Sertoli cell? a. It is the most immature form of sperm cell b. It secretes testosterone c. It secretes estrogen d. It acts as the blood-testis barrier Answer: d. The Sertoli cells are supportive cells to the germ cell/immature sperm cell. They secrete locally-acting molecules necessary for sperm cell survival and act as the blood-testes barrier—preventing autoimmune reactions against developing sperm cells.

Which is the most immature sperm cell called in the process of spermatogenesis?

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a. Spermatids b. Spermatogonia c. Primary spermatocytes d. Secondary spermatocytes Answer: b. The first cell in the line of spermatogenesis is called a spermatogonium or plural being spermatogonia. 5.

Where does the mature sperm in the male get stored in order to wait for ejaculation? a. Seminiferous tubules b. Ejaculatory duct c. Prostate gland d. Epididymis Answer: d. The epididymis is where sperm matures and where they are held until ejaculation takes place. They are held at the end of the epididymis.

What aspect of the semen in males makes up the most volume of this fluid? a. Sperm cells b. Seminal vesicle fluid c. Prostatic fluid d. Bulbourethral gland fluid Answer: b. The seminal vesicle fluid makes up 60 percent of the volume of semen. Sperm cells themselves make up just five percent of the total volume.

What structure of the male reproductive tract secretes fructose into the developing semen? a. Seminal vesicles b. Bulbourethral glands c. Prostate d. Ejaculatory duct

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Answer: a. The seminal vesicles secrete fructose in order to create sperm that has the nutrient in it for better sperm mobility. 8.

What part of the male reproductive tract secretes substances that temporarily coagulates sperm in the semen for ejaculation? a. Seminal vesicles b. Bulbourethral glands c. Prostate d. Ejaculatory duct Answer: c. The prostate gland is a gland in the male reproductive tract that makes substances for the temporary coagulation of semen in the ejaculate.

What molecule directly causes the corpus cavernosa and spongiosum to fill with blood during the erection? a. Testosterone b. Epinephrine c. Nitric oxide d. Vasopressin Answer: c. Nitric oxide will cause vasodilation of the arterioles and an increase in the blood in the corpus cavernosa and corpus spongiosum so that the penis can fill with blood during an erection.

10.

Which cells of the male reproductive tract will make testosterone? a. Leydig cells b. Sertoli cells c. Spermatids d. Spermatogonia Answer: a. The Leydig cells will release testosterone to promote male sexual characteristics. It causes the primary and secondary sexual characteristics—in utero and in puberty.

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CHAPTER EIGHTEEN: FEMALE REPRODUCTIVE SYSTEM This chapter first covers the anatomy of the female reproductive system, including the internal and external anatomic structures. The physiology of the menstrual cycle and female hormones are included in this chapter as well as the anatomy and physiology of the female breast. Finally, the embryological development of the female reproductive system is discussed in this chapter.

FEMALE REPRODUCTIVE ANATOMY The female reproductive system not only produces 23-chromosome gametes but it produces reproductive hormones and participates in the growth and development of the fetus in pregnancy. This system is located entirely in the pelvic cavity (except for the endocrine portion, the pituitary gland and hypothalamus. The gamete in this case is called the oocyte. The external female genitalia are referred to as the vulva. This includes a fat pad over the pubic bone called the mons pubis. This is covered with pubic hair after puberty but serves no other major function. It also includes the labia minora and the labia majora. These are the inner lips and the outer lips, respectively. The outer lips are covered with hair and are thicker and fattier than the inner lips. The labia minora are relatively thin and more pigmented. Figure 117 illustrates the female genitalia:

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Superior to the labia minora is the glans clitoris or clitoris. This is an erectile body of tissue that is as highly sensitive in females as the glans penis is in males—sharing the same embryonic origin. The hymen is a thin membrane that sometimes partially covers the entrance to the vagina. This is a membrane that leaves an opening for the exit of menstrual blood. The vaginal opening is the space between the labia minora. On either side of the vaginal opening are the Bartholin glands, also referred to as the greater vestibular glands. The vagina is a muscular canal that connects the cervix and uterus to the outside. It is about 10 centimeters in length. It is also the birth canal where the infant exits the body. There are outer walls that form ridges along the vaginal column. The fornix is the part of the vagina that is above the level of the cervix, which protrudes into the vaginal space. There is a fibrous adventitial layer on the outer aspect of the vagina and a middle layer of smooth muscle. The

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inner mucus membrane lines the vagina with folds of tissue called rugae. These rugae will flatten out as the vagina expands in childbirth. The Bartholin glands are near the surface of the body near the clitoris. They secrete mucus that keeps the vestibulum (the opening of the vagina) moist. These glands are embryologically similar to the bulbourethral glands or the Cowper’s glands in the male genitalia. The vagina consists of multiple microorganisms that are resident in the vagina to prevent infections from pathogenic bacteria and yeast organisms. The main bacterium found in the female vagina is the Lactobacillus bacterium, which secretes lactic acid that keeps the vaginal pH of below 4.5, which is relatively inhospitable to other bacterial types. The lactic acid also cleanses the vagina—a process that is disrupted and endangered when a woman uses douches. The ovaries are paired structures that are the equivalent of the male testes; these are the female gonads. Each is about 2-3 centimeters in diameter and slightly ovoid in shape. The ovaries are found in the pelvic cavity, supported by the mesovarium, which is an extension of the peritoneum connecting the ovaries to the broad ligament. The suspensory ligaments of the ovary contain the necessary ovarian blood and lymph vessels. There is also an ovarian ligament that attaches the ovary to the uterus. Figure 118 shows the microscopic view of the ovaries:

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The ovary has an outer layer of cuboidal epithelium that forms the ovarian surface. Deep to this is the tunica albuginea, which is the dense connective tissue structure that is similar to that in the male testicle to make the cortex of the ovary. The cortex forms a framework of sorts called the ovarian stroma, which forms the bulk of the ovary. Oocytes (egg cells) will develop on the outer layer of the stroma, surrounded by supportive cells. The oocyte plus the supporting cells is called a follicle. Beneath the cortex is what’s called the inner ovarian medulla, which is where the blood vessels, nerves, and lymph vessels exist in the ovary.

THE OVARIAN CYCLE AND OOGENESIS The ovarian cycle involves the predictable development of the female oocyte and the ovarian follicles during a woman’s reproductive years. This cycle is related to but not the same as the menstrual cycle. It involves oogenesis (which is the creation of the gamete) and folliculogenesis (which is the development of the follicle).

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The process of creating the female gamete is referred to as oogenesis. The oogonia are the female stem cells that form in utero during fetal development, dividing by mitosis similar to how the male spermatogonia divides. Unlike the male, however, the female process of oogenesis enters the primary oocyte stage before birth with arrest of this process during this stage of development until the woman becomes fertile. The arrest of development ends with the primary oogonium undergoing meiosis I but doesn’t go further until menarche, or the onset of menses in females. The process continues until menopause, when the oocytes no longer divide. There are millions of oocytes prior to birth but only 1-2 million at the time of the woman’s birth and this number falls further to 400,000 at the time of puberty. The number reaches zero at menopause. Ovulation or the release of an oocyte from an ovary doesn’t happen until sexual maturity is reached at menarche. Ovulation occurs roughly once every 28 days on average. The luteinizing hormone in the female reaches a peak prior to ovulation and starts the resumption of the meiosis I process in the primary oocyte so that it can become a secondary oocyte. While in males, this results in two cells, this doesn’t happen in females. One secondary oocyte gets most of the cytoplasm while the other receives very little and becomes a nonfunctional polar body. The polar body might or might not complete its own meiosis but it will disintegrate. Rather than the four cells that come from the male spermatogenesis process, only one cell survives to become ovulated. There is one oogonium, two diploid primary oocytes (arrested in meiosis I). One goes on to complete meiosis to become a secondary oocyte, while one becomes a polar body (the secondary oocyte is haploid, with only 23 chromosomes). The secondary oocyte doesn’t actually complete its meiotic process until after it gets fertilized. Meiosis II in the secondary oocyte happens after fertilization leading to a haploid ovum that becomes the diploid zygote instantly. This is the basis of human life and is the first cell of the embryo, containing both chromosomes from the male and chromosomes from the female. The female ovum is considerably larger than the male sperm and contains all of the mitochondria and organelles of the zygote. The sperm cell does not contribute any cytoplasm to the process. All the mitochondrial DNA is inherited by the maternal side/the ovum. 405

FOLLICULOGENESIS Folliculogenesis is the process of making a female follicle. In general, just one follicle is made every 28 days. All of the other follicles developing at that time undergo atresia or ovarian follicle death. Follicles themselves undergo a process of development, beginning as a primordial follicle and progressing to become a primary, secondary, and tertiary follicle. This contains a primary oocyte until right before ovulation occurs. There are small primordial follicles in all newborn females, which are the only type of follicle seen before menarche. These consist of a single layer of supporting cells called granulosa cells that surround the oocyte. These stay in the same state until the follicle gets “recruited.” A few primordial follicles will get recruited every day so that there will be a pool of immature follicles called primary follicles. These granulosa cells are initially squamous and later become cuboidal in shape as they divide, grow, and proliferate. When the granulosa cells proliferate, the cell becomes a secondary follicle. These secondary follicles increase in size and add an outer layer to the follicle, consisting of connective tissue, supporting blood vessels, and theca cells that produce the different types of estrogens. There is a membrane produced by the primary oocyte within the follicle, called the zona pellucida. Fluid known as follicular fluid forms between the granulosa cells, collecting into the antrum—a pool of follicular fluid. The follicle filled with fluid becomes an antral follicle, also known as a tertiary follicle. While several follicles will reach the tertiary or antral stage at the same time but almost all of these will undergo atresia. One (usually) continues to grow and develop until the time of ovulation, when it is expelled as the secondary oocyte surrounded by several layers of granulosa cells from inside the ovarian follicle. Figure 119 shows the different stages of folliculogenesis:

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HORMONES AND THE OVARIAN CYCLE The process of going from a primordial follicle to an early tertiary follicle takes about two months in female humans. The end of the cycle involves a small number of tertiary follicles and the eventual ovulation of the secondary oocyte. These changes happen under the control of the same hormones that regulate spermatogenesis in males, such as GnRH (from the hypothalamus), LH, and FSH (which both come from the anterior pituitary gland).

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Females produce GnRH by the hypothalamus. This is a signal to the anterior pituitary gland, which makes FSH and LH. These hormones will travel to the ovaries, where they bind to the granulosa and thecal cells of the follicles. FSH will stimulate the growth of the follicles, allowing for 5-6 tertiary follicles to grow exponentially. LH will cause both the granulosa cells and the theca cells to make estradiol, which is the major type of estrogen. This is the follicular phase of the menstrual cycle. The more granulosa cells and theca cells in the follicle, the more estrogen is produced by the structure. Large follicles produce enough estradiol to affect the serum estrogen concentration. This will feed back to the hypothalamus and pituitary gland to lessen the release of GnRH, FSH, and LH. This decline in FSH causes atresia of those follicles that aren’t already past a certain point in the cycle. The dominant follicle will survive this atresia process and will continue to progress. This is the one that will be released as an oocyte. The dominant follicle begins to secrete more estrogen than all of the previously developing follicles made altogether before the atresia occurred. The high estrogen level causes the anterior pituitary gland to release LH and FSH that causes the LH surge. This is what causes the ovulation process to occur. It stimulates the resumption of meiosis to make a secondary oocyte (and a polar body). Enzymes called proteases are released to break down the structural proteins in the ovarian wall, bursting the large antrum so that the oocyte can be released into the peritoneal cavity. The surge of LH will alter the granulosa cells and theca cells remaining in the follicle after the oocyte is ovulated. This is referred to as luteinization, turning the leftover follicle into the corpus luteum, which starts the luteal phase. These cells will produce large amounts of progesterone, which is necessary for the maintenance of pregnancy. Progesterone will feed back to the hypothalamus and pituitary gland, resulting in low GnRH, LH, and FSH levels and there are no new follicles developing at this time. The corpus luteum occurs in the luteal phase of the ovarian cycle. If a pregnancy isn’t established within 10-12 days, the corpus luteum will stop functioning in 12-14 days, leading to

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the corpus albicans, which ultimately degrades over several months. FSH and LH are stimulated again and the cycle takes place all over again with new tertiary follicles.

FALLOPIAN TUBES These are also referred to as the uterine tubes or oviducts. These are the tubes in which the oocyte after ovulation travels from the ovary to the uterus. These are paired structures on either side of the uterus. There is the isthmus, which connects the fallopian tube to the uterus, the infundibulum (which flares out at the end of the fallopian tube), and fimbriae, which are fingerlike projections that extend out to the ovary. The ampulla is the midsection of the fallopian tube, where the fertilization process occurs. This is a three-layered tube with an outer serosa, inner smooth muscle layer, and an inner mucosal layer. The inner lining has ciliated cells that beat in the direction of the uterus. The uterine tube receives the oocyte, which is released into the peritoneal cavity in the vicinity of the fimbriae. The contraction of the uterine tube every 4-8 seconds will cause the fimbriae to sweep over the ovaries to accept the oocyte. The cilia pick up the oocyte and carry it down the fallopian tube. The cilia beat more strongly in the presence of estrogen. Muscular contraction of the uterine tube also contributes to the movement of the oocyte. Fertilization usually takes place in the ampulla. After fertilization, the resulting zygote will divide into two, four, and eight cells. It is made of multiple cells by the time it reaches the uterus for implantation. If the egg isn’t fertilized, it will degrade in the uterus or in the fallopian tube, where it is shed as part of the menstrual period.

CERVIX AND UTERUS The uterus is an organ that is largely muscular. Its function is to support the embryo and fetus during pregnancy. It is only about 2-3 inches in dimension when not pregnant. There are three segments to the uterus: the fundus (which is above the isthmus of the fallopian tubes), the body or corpus (which is the midsection of the uterus), and the cervix (the narrower lower part of the uterus that opens out into the vagina). The cervix will facilitate fertilization by secreting mucus that is hospitable to sperm during the time of ovulation.

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There are several supportive ligaments to the uterus. The broad ligament is the major supporting structure of the uterus, formed by folding peritoneal tissue. The round ligament is what attaches the uterus to the labia majora—attaching to the uterus near the fallopian tubes. There is also a uterosacral ligament that connects the cervix to the posterior aspect of the pelvic wall. There are three layers to the uterus. The outer wall is called the perimetrium (which is the serous layer). The myometrium is the middle layer (a layer of smooth muscle that contracts the structure). The endometrium is the inner lining of the uterus. It consists of two layers of its own. There is the stratum basalis and the stratum functionalis. The stratum basalis is next to the muscular layer and does not shed in menstruation. On the other hand, the stratum functionalis will grow and thicken in response to the estrogen level of the woman. In the luteal phase, there are branches of the uterine artery known as the spiral arteries that supply the functionalis layer. They provide circulation should implantation occur. If it doesn’t happen, the stratum functionalis layer will be shed in menstruation. It is the progesterone that causes maturation of the stratum functionalis. This prepares the layer for implantation of the fertilized oocyte. When the corpus luteum fails at the end of the luteal phase, the stratum functionalis fails to be supported and, under the influence of prostaglandins, the spiral arteries of the endometrium will constrict, starving off the stratum functionalis and causing it to be shed in the process of menstruation.

MENSTRUAL CYCLE PHYSIOLOGY The menstrual cycle involves the series of changes that occur in the uterus, ovaries, and fallopian tubes that result in the rebuilding, preparation, and shedding of the stratum functionalis layer of the uterus. Day one of the menstrual cycle is the first day of menses. The cycle goes from the first day of bleeding to just before the first day of the next bleeding cycle. The length of the menstrual cycle is about 22-35 days in length—an average of 28 days. There are three phases of the menstrual cycle: the menses phase, the proliferative phase, and the secretory phase.

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The menses phase happens when the uterine lining is first shed. It lasts about 2-7 days and is a time of low progesterone levels, low FSH levels, and low LH levels. It is the decline in progesterone from the dying corpus luteum that triggers this phase. The stratum functionalis layer is shed during this period of the cycle. The proliferative phase happens after the menstrual phase. The endometrium begins to proliferate and there are increased estrogen levels on the part of the granulosa and theca cells of the tertiary follicles. The estrogen stimulates the building up of the endometrial lining. The high estrogen levels first lead to a decrease in FSH from a negative feedback loop. Then the dominant follicle will produce large amounts of estrogen, which causes the LH surge and ovulation to occur. Ovulation occurs at about day 14 of the menstrual cycle. This marks the end of the follicular phase. The ovulated oocyte is picked up by the fimbriae and travels down the fallopian tube. The vagina becomes more hospitable to sperm so that fertilization can ultimately occur. There begins to be a high progesterone level from the corpus luteum, which triggers maturation of the stratum functionalis in preparation for the fertilized egg. The endometrial glands will secrete a glycogen-rich fluid in preparation for implantation. This is nourishing fluid for the zygote, should it arrive in the uterus. This is why it’s called the secretory phase. Spiral arteries are rich during this phase so that they can supply the uterine lining if there is fertilization. If there is no fertilization, the secretory phase ends with the degrading of the corpus luteum, triggering the next cycle.

BREAST ANATOMY AND PHYSIOLOGY The breasts are considered accessory organs of the female reproductive system. Their major function is to supply milk in the process of lactation or breastfeeding. The breast consists of fatty tissue, milk-producing lobules, and ducts. The ducts end in a nipple that is surrounded by a pigmented area called the areola. There are lubricating glands in the areolae that secrete fluid during lactation so as to protect the nipple from chafing. When the baby nurses, the entire areolar region is taken in by the infant’s mouth to draw milk out of the glands. Figure 120 shows the anatomy of the breast tissue:

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Breast milk is produced by the mammary glands, which are actually modified sweat glands. Milk leaves the nipple via 15-20 lactiferous ducts that open out onto the surface of the nipple. Each of these go into the lactiferous sinus that connects to a lobe that contains alveoli, which are made from milk-secreting cells. These alveoli will change greatly in size depending on whether or not there is milk in them. Milk made in these alveoli will pass into the lactiferous sinuses, where it can be drawn out through the ducts via the act of suckling.

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FEMALE REPRODUCTIVE DEVELOPMENT The development of the female reproductive system in utero was described in the previous chapter. Remember that all embryos are phenotypically female until the male Y chromosome causes factors to be released that cause the development of male genitals and male reproductive structures. The female structures come from the Mullerian ductal system, which gives rise to the female parts of the reproductive tract. More changes happen in puberty in females. During this time, the primordial follicles begin to develop and menarche begins. The onset of menarche actually comes late in the process of puberty. Other changes that happen during female puberty include the following: •

Deposition of fat on the breast and hip areas

•

Breast growth and development

•

Broadening of the pelvis and the growth of both axillary and pubic hair

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KEY TAKEAWAYS •

The external genitalia consist of the clitoris, labia minora, labia majora, and mons pubis.

•

The internal female reproductive system involves the uterus, cervix, vagina, fallopian tubes, and ovaries.

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The process of oogenesis involves the taking of the oogonia through mitosis and meiosis to create just one secondary oocyte, which is fertilized.

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The process of folliculogenesis involves the development of primordial follicles, which grow and change to become primary, secondary, and tertiary (or antral) follicles.

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The menstrual cycle involves changes in the uterine lining that will grow in the follicular phase, mature in the secretory phase, and shed in the menstrual phase.

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The breasts are the site for milk production during lactation or breastfeeding.

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QUIZ 1. The highly sensitive erectile structure in the female genitalia is called what? a. Labia minora b. Clitoris c. Mons pubis d. Hymen Answer: b. The clitoris is the erectile structure that is sexually responsive in the female reproductive system. It is the embryological equivalent of the glans penis. 2.

What is the thin membrane called that partially covers the vaginal opening in the female external genitalia? a. Labia minora b. Clitoris c. Mons pubis d. Hymen Answer: d. The hymen is the thin membrane that partially covers the vaginal opening prior to a woman’s first sexual intercourse. It only partially covers the vagina to allow for the exit of menstrual blood during menstruation.

Which structure connects the ovaries to the uterus? a. Broad ligament b. Suspensory ligament c. Mesovarium d. Ovarian ligament Answer: d. The ovarian ligament connects the ovaries to the uterus itself; the other supporting structures are related to the ovaries and help keep them fixed in the pelvic cavity.

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What is the outermost layer of the ovaries made of? a. Tunica albuginea b. Ovarian follicles c. Cuboidal epithelium d. Ovarian medulla Answer: c. The outermost layer of the ovaries consists of cuboidal epithelium, with the tunica albuginea just inside the cuboidal epithelium, forming the cortex of the ovaries.

When does the secondary oocyte complete meiosis in the female reproductive cycle? a. After it is fertilized b. Just before ovulation c. At the time of menarche d. Just after ovulation Answer: a. The secondary oocyte must first be fertilized before it can undergo the last stages of meiosis.

Which is the main type of follicle found in female children? a. Tertiary follicle b. Secondary follicle c. Primary follicle d. Primordial follicle Answer: d. Primordial follicles are the only type of follicle seen in female children; these consist of a single layer of cells that support the developing egg cell.

How long does the process of folliculogenesis take place? a. Two weeks b. 28 days c. Two months 416

d. Six months Answer: c. It takes two months for a primordial follicle to become a tertiary follicle that gets ovulated. Follicles are recruited every day and there are several tertiary follicles; however, only one usually gets released in the ovulation process. 8.

What hormone is responsible for the development and continued growth of the female follicle in the menstrual cycle? a. FSH b. LH c. GnRH d. Estradiol Answer: a. Under the stimulation of FSH or follicle-stimulating hormone, the follicles will continue to develop until there is a negative feedback onto the pituitary and hypothalamus, reducing the FSH level and resulting in atresia of all but the dominant follicle.

In the female fallopian tube, where does fertilization usually take place? a. Fimbriae b. Isthmus c. Ampulla d. Infundibulum Answer: c. The ampulla is the central part of the fallopian tube and is where fertilization usually takes place. The isthmus is the connecting part to the uterus, while the infundibulum is the far lateral aspect of the fallopian tube, which opens into projections called fimbriae.

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Which is the topmost section of the uterus called? a. Isthmus b. Fundus

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c. Corpus d. Cervix Answer: b. The fundus is the topmost section of the uterus and lies above the isthmus, which is the opening of the fallopian tubes out of either side of the uterus.

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CHAPTER NINETEEN: DEVELOPMENTAL ANATOMY AND PHYSIOLOGY This last chapter includes a discussion of genetics and how it applies to human phenotypes. Fertilization is more completely covered than in prior reproductive system chapters and the development of the embryo is explained in detail. As the embryo becomes a fetus at eight weeks gestation, the development continues; this is covered as the final topic of this chapter.

GENETICS AND DEVELOPMENT There are twenty-three pairs of human chromosomes. In a karyotype, the geneticist will lay out the pairs of chromosomes from 1 through 22. There is no 23rd chromosome pair. Instead there are the sex chromosomes, which determine the person’s gender. There are two X chromosomes, leading to a 22, XX chromosome pattern, in females. In males, there is an X and a Y chromosome, leading to a 22, XY chromosome pattern. The remaining 22 chromosomes are known as autosomal chromosomes. Each will contain up to thousands of individual genes that code for a specific protein. The genetic makeup of the individual is called their genotype, while the physical makeup that comes from the chromosomes is called the phenotype. One half of the 46 chromosomes a person has will come from each parent. This happens when the sperm and egg cell unite during fertilization. Each chromosome of the pair will contain genes coding for the same basic protein but there will be one copy, called an allele, inherited from the sperm and one copy inherited by the egg. The alleles for any given gene may be the same and will code for the same thing. In other cases, the alleles would be different. In some cases, there is a dominant allele and a recessive allele; in other cases, there will be codominance of the alleles, with both genes having an effect on the physical makeup or the phenotype of the individual. Having two identical alleles for a given gene indicates being homozygous for the state. Having two different alleles for a given gene means being heterozygous for the state. The dominance of one gene over another gene can be complete or incomplete. When it is incomplete, this is 419

called incomplete penetrance. Codominance means that neither of the genes has dominance over the other and both are expressed. Generally, there is more than one gene that codes for a specific characteristic. There are at least eight genes, for example, that determine the person’s eye color in humans. There are three alleles that encode for the ABO blood types on the RBCs. Still other diseases will have just one gene that encodes for a specific protein—a mutation of which will cause disease. An example is cystic fibrosis, which is an autosomal recessive disease that involves a single gene defect. A person can be the carrier for a disease in recessive conditions and will not have the disease. For example, it requires two copies of a mutated cystic fibrosis gene to actually have cystic fibrosis.

INHERITANCE PATTERNS Much of what is understood regarding how genetic diseases are inherited or how a phenotype is created comes from the work of Gregor Mendel in the mid-1800s. While he didn’t understand genes or chromosomes, he did identify inheritance patterns in pea plants that paved the way for Mendelian genetics. It became understood that certain gene characteristics were dominant, while others were recessive. This inheritance pattern applies to traits, like height, eye color, hair type, and—even more complex—things like intelligence and other physical features. According to Mendelian genetics, there will always be a dominant and a recessive allele. In practical genetics, however, there are codominant genes and incomplete penetrance, which do not follow the rules of Mendelian genetics. Things like ABO blood types are codominant, which involves genes that do not have dominance over each other. A person can be homozygous for a dominant trait and will always give a dominant gene to their offspring. If a person is heterozygous for a trait, they have one copy of a dominant gene and one copy of a recessive gene. This will still, under Mendelian genetics, be a dominant phenotype because the dominant gene will prevail and will “hide” the recessive gene. They can pass on the dominant or recessive trait to their offspring. The person who is homozygous for a

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recessive trait will have the recessive trait phenotypically and will only pass the recessive trait on to their offspring. Having two heterozygous parents means that each will give a copy (or allele) to their offspring. They can give a dominant or recessive allele. With Mendelian inheritance rules, three of their offspring will have the dominant trait, while one (or 25 percent) will have the recessive trait. These are, of course, averages and estimate the odds or probability that a child will be homozygous dominant, heterozygous dominant, or homozygous recessive. This 3:1 ratio will be seen in this circumstance. A heterozygous dominant person will have a 100 percent chance of passing on the dominant trait to their offspring. Finally, if a heterozygous dominant person and a homozygous recessive person have a child, the dominant trait is only passed to the child half or 50 percent of the time. This means that there will be the statistical probability that half of the children will have the dominant trait (all of whom will be heterozygous themselves) and half of the children will have the recessive trait (and will be homozygous recessive). Remember, this applies to just one gene and there are thousands of genes that get transmitted from two parents’ genomes to their offspring, making endless combinations of phenotypes in the child. An autosomal dominant disorder or autosomal dominant trait is one in which the person has the trait on one of the 22 pairs of chromosomes. Examples of diseases like this include neurofibromatosis I and Huntington disease. As mentioned, there is a 50 percent chance of passing the gene on if the person is heterozygous and a 100 percent chance of passing on the gene if the person is homozygous for the disease. Marfan syndrome and achondroplasia are two diseases that are passed in this way. An autosomal recessive pattern is a disease that is only seen when the person is homozygous for the recessive trait. If the dominant gene is present at all, it would hide the recessive trait and the person won’t have the disease. This type of person would instead be called a “carrier.” Carriers may never know they have the genetic trait. An example of an autosomal recessive disorder is cystic fibrosis. Because the trait is relatively common, about 1 in 2000 people will be born with the disease. Only 25 percent of children of people with the mutated allele will have

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the disorder; the rest will be spared (although half will also be carriers). Other autosomal recessive diseases include Tay-Sachs disease, phenylketonuria, and sickle cell disease. X-linked disorders are a little more complex. Most are autosomal recessive in which the woman is a carrier of the disease. The mother will give an X-chromosome to each of her children but the father will give either an X-chromosome or a Y-chromosome. Because there is no matching healthy X chromosome in males, usually only boys get an X-linked disorder, although it is technically possible but rare to have females with an X-linked recessive trait. Half of all of the child’s boys will have the disease and half of the daughters will be carriers. X-linked dominant diseases are much rarer; however, vitamin D-resistant rickets is one of these diseases. Common X-linked recessive inherited diseases include hemophilia, color blindness, and certain types of muscular dystrophy. The most common scenario is the case of a female carrier (who will not have the disease) and a male who doesn’t have the disease. In such cases, half of the boys will get the mutated recessive gene and will get the disease. Half of the daughters will themselves be carriers. Males will either have the disease or they won’t; they cannot be carriers. In reality, there are things like incomplete dominance, in which a heterozygous person will express features of the dominant and a recessive trait. This can involve things like curly hair and straight hair. While curly hair is dominant, it can be incompletely expressed, leading to a child who just has wavy hair. Codominance involves equal inheritance of both alleles. This is seen in the ABO blood typing situation. A person who has the AB blood type has inherited the A allele from one parent and the B allele from the other parent. People with type O have neither the A allele nor the B allele in their genotype and neither of these receptors on their cell surface. There are some recessive and dominant alleles that are considered lethal. A recessive lethal disease is Tay-Sachs disease, in which there is a neurological condition that causes uniform death prior to five years of age. This is a single gene defect that is not compatible with life.

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Dominant lethal inheritance patterns are rarer because neither homozygotes for the disease nor homozygotes survive. Many of these mutations result in miscarriage or still birth. An example that does not result in stillbirth is Huntington disease. People die from the disease but not until many have already had children who have a 50 percent chance of also having the disease. It’s the late onset of the disease that makes this dominant lethal disease heritable. An allele can be mutated, also called a “mutation.” This is a defect in the DNA sequence that results in a change in the protein. Mutations can be spontaneous or secondary to environmental issues, like viruses, cigarette smoke, radiation, or toxins. This may result in no change in the phenotype but it can also be the cause of a miscarriage or, in the case of mutations of certain cells after differentiation, cancer. Most cancerous cells result from DNA mutations in the affected cancerous cell. There are several chromosomal disorders, which involve too many or two few chromosomes and several genes affected. A trisomy involves too many of a particular chromosome. Down syndrome (trisomy 21), Edward syndrome (Trisomy 18), and Patau syndrome (trisomy 13) are all autosomal trisomy syndromes with only Down syndrome being compatible with long life. A monosomy involves just one chromosome when there should be two. This is compatible with life only in Turner syndrome, which is a 22, XO disease. The female will have just one X chromosome and will not be able to have children.

FERTILIZATION Fertilization involves the uniting of oocyte and sperm cell to make a zygote, which is a diploid cell that has 46 chromosomes from both the sperm and the egg. This is a totipotent cell that can develop into any type of cell in the human body. Figure 121 shows a picture of fertilization:

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After intercourse, there are hundreds of millions of spermatozoa released into the vagina. These must overcome the acidity of the pH and the cervical mucus. Thousands are already destroyed by phagocytic uterine leukocytes before they reach the egg. Only a few thousand cells actually get into the leukocyte. The journey takes place over 20-120 minutes. They can survive for 3-5 days in the uterine environment until the time of fertilization. The egg, on the other hand, can survive just 24 hours before it degrades. There is capacitation going on. This includes getting rid of cholesterol in the head of the sperm so it can release its chromosomes better and can penetrate the egg more easily. This will help the lysosomal enzymes, or digestive enzymes, to be released that will ultimately aid in penetration. The passage of the egg takes place over 72 hours, which will need fertilization to survive as the egg will otherwise be degraded along this pathway. There are two layers surrounding the oocyte during its travel. These are the corona radiata (a layer of granulosa cells) as well as the 424

zona pellucida, which will involve a glycoprotein layer that surrounds the cell’s plasma membrane. There are chemical attractants that attract the sperm to the egg, released by the corona radiata. The sperm must burrow through the corona radiata to reach the zona pellucida. This triggers the acrosomal reaction, in which the acrosome releases enzymes that clears a path through the zona pellucida (the acrosome is the cap on the sperm cell). There are spermbinding receptors on the oocyte plasma membrane that attract the sperm. Once one sperm does this, its head and mid-piece enter the oocyte interior by fusing with the cell membrane. To prevent polyspermy (more than one spermatozoon entering the egg cell), there is the fast block, which depolarizes the egg cell membrane to prevent fusion of additional sperm cells. This lasts about a minute and causes an influx of calcium ions into the egg cell. Because of this, the cortical reaction takes place, involving cortical granules just inside the egg cell membrane. These will release zonal inhibiting proteins and mucopolysaccharides into the space between the plasma membrane and the zona pellucida. These destroy sperm receptors so no sperm cells can bind. The mucopolysaccharides then coat the zygote to create a hardened zona pellucida, called the fertilization membrane.

THE ZYGOTE At the time of fertilization, the secondary oocytes are arrested in metaphase of meiosis II. This is completed after fertilization, with a second polar body created and ejected. The two haploid nuclei called pronuclei will migrate to one another and fuse together. The male and femalederived DNA will intermingle and resulting in a single-celled diploid zygote. About one percent of the time, two eggs are released and fertilized. This results in dizygotic or fraternal twins. These are nonidentical. Less commonly, a zygote can divide into two separate offspring during early development. This results in monozygotic or identical twins. Splitting usually occurs when there are about 70-100 cells present but it can occur at the two-cell stage. The later this happens, the greater is the likelihood that the zygote and embryo will have the same placenta.

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EMBRYOLOGIC DEVELOPMENT Embryological age is determined from the weeks after conception and not the weeks after the first menstrual period (which is what’s done when determining how far along a pregnancy is). The former determination is called the weeks’ gestation. The first two weeks of gestation are called the pre-embryonic stage. Weeks 3-8 are called the embryonic stage with the products of conception called an embryo. At the ninth week of gestation, the embryo becomes a fetus. It is called this until birth. By the end of the embryonic phase, all of the organ systems are in place but are rudimentary.

PRE-IMPLANTATION PHASE Right after fertilization, the zygote is referred to as a conceptus with all of its membranes attached. It gets propelled by cilia and peristalsis through the fallopian tubes and undergoes several mitotic cell divisions without an appreciable increase in size. Each daughter cell from this conceptus is called a blastomere. Figure 122 shows the conceptus before implantation:

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The cells become a 16-cell conceptus at about three days after fertilization. These look like a solid mass of cells called the morula. It floats freely inside the uterus for a few days and divides to the 100-cell stage, using the nutritive endometrial secretions discussed in the previous chapter. The ball of cells begins to secrete its own fluid, resulting in a fluid-filled cavity referred to as a “blastocoel.” At this stage, the conceptus is called a blastocyst. There is an inner cell mass that goes on to make the embryo and outer cells called trophoblasts (that become the chorionic sac and the fetal part of the placenta). Figure 123 shows what the blastocyst looks like:

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IMPLANTATION At the end of the first week, implantation occurs and the conceptus (the blastocyst) imbeds into the lining of the uterus. It usually implants in the posterior wall or in the fundus. About half to three-fourths of the blastocysts will not implant and menses will occur. This is why pregnancy often takes several ovulation cycles in order to achieve a pregnancy. At the time of implantation, the trophoblast cells fuse to form the syncytiotrophoblast, which is a cell body that digests endometrial cells in order to firmly secure the blastocyst to the uterine wall. In response, the uterine mucosa envelopes the blastocyst. The trophoblast secretes HCG (human chorionic gonadotropin), which feeds back to the ovaries so that the corpus luteum does not die. This supports the pregnancy. Just a few days after implantation, the HCG level will be high enough to cause a positive at-home pregnancy test. The implanted embryo begins to organize with the blastocyst forming several layers. Some will grow to become extra-embryonic membranes needed to support the growing embryo. These are the amnion, the yolk sac, the allantois, and the chorion. First, there is a two-layered disc that forms in the inner cell mass along with a space called the amniotic cavity between the inner cell mass and the trophoblast. The upper layer of the disc is called the epiblast, while the lower layer is the hypoblast. This extends into the amniotic cavity, creating a membranous sac that becomes the amnion. The amnion fills with amniotic fluid that comes from the maternal plasma. Ultimately, the fluid comes from the fetal kidneys by the eighth week of gestation. The embryo floats within the amniotic cavity to protect it from trauma. Figure 124 illustrates what these structures look like:

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The inner aspect of the embryonic disc is the hypoblast. It extends into the blastocyst cavity to form the yolk sac. This provides primitive circulation to the developing embryo for the second and third week of embryonic development. The placenta will nourish the embryo at about week four of gestation. The yolk sac has been greatly reduced in size, with its main function to be the source of both blood cells and germ cells (that will make the fetus’s gametes). There is a finger-like extension of the yolk sac that develops into the allantois, which is an excretory duct that forms the fetal bladder. The stalks of the yolk sac and allantois form the outer aspect of the human umbilical cord. The chorion is the last extra-embryonic membrane, surrounding all other layers.

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EMBRYOGENESIS The cells of the two-layered disc of the embryo become three-layered through what’s called gastrulation. There is an indentation in the disc called the primitive streak along the surface of the epiblast. There is a node at the tail end of the primitive streak (the caudal end) that secretes factors that cause the migration of cells through the primitive streak, forming two more layers. The first is the endoderm that replaces the hypoblast, lying just next to the yolk sac. The second is the middle layer, called the mesoderm. The cells that were the nonmigrating epiblast cells become the ectoderm. These three layers are called germ layers. They turn into specific structures of the fetus. The ectoderm becomes the nervous system, sensory organs, hair, nails, and skin. The mesoderm gives rise to the muscles, skeleton, connective tissue, heart, kidneys, and blood vessels. The endoderm forms the GI tract lining, the liver, the lungs, and the pancreas.

PLACENTAL DEVELOPMENT The endometrial decidual cells will nourish the cells of the embryo prior to week four. Between week four and week twelve, the placenta develops and takes over nourishment of the embryo and fetus. The mature placenta comes from both the embryo and the mother. The placenta is connected to the conceptus via the umbilical cord, which has two umbilical arteries and one umbilical vein. The cord is covered by amnion and the vessels are surrounded by Wharton’s jelly, which is a mucus-containing connective tissue. The maternal portion of the placenta comes from the decidua basalis or stratum basalis of the endometrium. The embryonic portion comes from the syncytiotrophoblast and the underlying trophoblast cells called cytotrophoblast cells. These form the chorionic membrane along with some extra-embryonic mesoderm cells. This becomes the chorion. There are finger-like projections from the chorion called chorionic villi that form the fetal portion of the placenta. There are fetal mesenchymal cells (from the mesoderm layer) that form the three umbilical blood vessels. Figure 125 illustrates the basic anatomy of the placenta:

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Full placentation takes place by week 14-16 of gestation. The placenta provides respiration, nutrition and excretion, and endocrine function to the fetus. It takes blood from the fetus via the umbilical arteries, after which capillaries in the chorionic villi filter fetal wastes to return oxygenated blood to the umbilical vein and back to the fetus. The fetal and maternal circulation do not normally mix, with diffusion of oxygen, CO2, and lipid-soluble substances and facilitated diffusion for other substances. Iron and amino acids get to the fetus via active transport. The chorionic villi that act as the surface area for two-way exchange of substances from the maternal blood and the fetal blood. The villi become more branched and thinner throughout gestation. Things like alcohol, barbiturates, nicotine, some pathogens, some other drugs, and antibiotics can cross the placental barrier, potentially being toxic to the fetus.

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ORGAN FORMATION Organ formation is called organogenesis. This happens after gastrulation, which is the formation of the three germ layers and the folding of the layers to form a tube. Neurulation involves the formation of the central nervous system from the ectoderm cells. There are neuroectodermal tissues along primitive fold that become the neural plate. These fold upward to make the neural fold that comes together to make the neural tube. The tube sits on top of a mesoderm-derived structure called the notochord. The notochord develops into the nucleus pulposus of the intervertebral discs. The notochord divides into blocks called somites that differentiate into the axial skeleton, dermis, and skeletal tissue. The anterior part of the neural tube will dilate and become vesicles that form the structures of the brain. The embryo starts out flat and then curves around to form a cylindrical shape through embryonic folding. It develops a distinct head and tail end. The embryo takes in a portion of the yolk sac that becomes the abdomen. This folding will create an endodermal-lined tube called the primitive gut. Organogenesis is complete by the end of the eighth week of gestation. The heart begins beating by the beginning of the fourth week and pumps blood by the fifth week. The liver starts making RBCs by the fifth week; this eventually gets taken over by the bone marrow. Eye pits form during this time and limb buds will form. The beginnings of the lungs also occurs around the fifth week. Fetal movement starts at the sixth week and the intestines form around the umbilical cord because it does not yet fit into the abdomen. The fingers and toes are formed by apoptosis of certain cells in the paddles that are initially the hands and feet. By week seven, there are facial features, lenses, ears, and nostrils. By eight weeks, the major aspects of the brain are in place. The head is as large as the rest of the body and the external genitalia are in place (although the phenotype at that time is always female). Bone begins to replace cartilage via ossification with an embryo that is three cm in length from crown to rump at the end of the embryonic period.

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FETAL DEVELOPMENT The fetal period starts at the ninth week of gestation until birth. While organogenesis has taken place, these organs are rudimentary and need to be fully developed. Sexual differentiation happens between the ninth and the twelfth week. If the fetus is a female, the Mullerian ducts predominate; if the fetus is a male, the Wolffian ducts predominate and the Mullerian duct structures degenerate. The cloaca becomes the rectum and urethra. In females, the cloaca develops into the vagina, rectum, and urethra. The fetus develops a fetal circulation that is integrated with the placenta. The heart starts out as two parallel tubes made from mesoderm and lined with endothelium. This further differentiates into four chambers with shunts that go away at the time of birth. The shunts allow for shortcuts that shunt blood away from the fetal liver and lungs, which are immature. The umbilical vein empties oxygenated blood into the inferior vena cava, which basically bypasses the liver. The liver is bypassed via the ductus venosus shunt, which allows just a little blood to get to the liver. The lungs are bypassed via the foramen ovale, which connects the atria together. The ductus arteriosus is a shunt within the pulmonary artery, which shunts blood into the aorta, bypassing more of the lung circulation. Other organs develop in the fetus besides the circulation. The weeks nine through 12 allow for brain expansion, elongation of the body, and ossification. Fetal movements continue and are partially controllable. Bone marrow kicks in and erythrocytes are made by this structure. Bile is produced by the liver and the fetus will swallow amniotic fluid. The nails develop and the fetus is about nine centimeters in length from crown to rump. From weeks thirteen through sixteen, there is sensory organ development. The eyes will blink but will not open. Sucking motions begin and the ears move upward. The eyes move closer together and the scalp starts to grow hair. The kidneys will make urine and meconium (fetal feces) starts to build up in the fetal intestines. From weeks sixteen through twenty, movement becomes stronger and the mother will feel these fetal movements. The sebaceous glands will form a waxy substance called vernix caseosa

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that protects and moisturizes the fetal skin. Lanugo hair will cover the whole body but is eventually shed by the time of the infant’s birth. Weeks 21 through 30 are marked by weight gain and bone marrow maturation. Myelination of axons occurs but doesn’t complete until a child reaches adolescence. The lungs will produce respiratory surfactant that reduces surface tension in the alveoli. The testes descend and, at 30 weeks, the crown-rump length is 28 centimeters. The fetus grows subcutaneous fat at 31 weeks through birth, which fills out the hypodermis to protect the fetus from thermal insults. The nails grow out and the lanugo hair is shed. The fetus weighs about 5.5 to about 8.8 pounds at the time of birth with a crown-rump length of 14 to 16 inches or 35 to 40 centimeters. The end of pregnancy happens at about 38.5 weeks or 270 days after conception, when the fetus is mature enough to survive outside of the womb.

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KEY TAKEAWAYS •

Genetics is based on 23 pairs of chromosomes containing thousands of different genes that code for different proteins.

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Mendelian genetics allows for dominant and recessive genes, although there are many cases of codominance and incomplete penetrance of dominant genes.

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Fertilization allows for one egg to meet with just one sperm cell to create a zygote.

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The conceptus begins to divide immediately, forming a ball of cells called a morula and a more complex structure called a blastocyst (which is fluid filled).

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The placenta is formed from components of the fetus and the maternal tissues and acts as an endocrine, respiratory, and nutrient/waste organ.

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Most of the organs have developed by eight weeks gestation, although they are not fully functional by that time.

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The fetal stage starts at nine weeks gestation and is a time of maturation and growth of the fetus.

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A full germ gestation is about 270 days from conception to birth or about 38.5 weeks in total.

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QUIZ 1. When looking at a male karyotype, the chromosomes will be numbered and matched. The karyotype will be listed how? a. 22, XX b. 22, XY c. 23, XY d. 23, XX Answer: b. The chromosome pattern on the karyotype will be 22, XY. There are 22 pairs of autosomal chromosomes; there will be an X and a Y chromosome, indicating that this is a male. 2.

Which genetic trait or disease is inherited in a codominant fashion? a. ABO blood type b. Eye color c. Cystic fibrosis d. Huntington disease Answer: a. ABO blood types are codominant traits in which there is no dominance of one gene over another gene. Eye color is polygenic, meaning several genes are involved. Cystic fibrosis is autosomal recessive and Huntington disease is autosomal dominant.

What disorder is considered a dominant lethal disorder? a. Tay-Sachs disease b. Neurofibromatosis I c. Cystic fibrosis d. Huntington disease

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Answer: d. Huntington disease is a dominant lethal disorder, incompatible with long life. The major problem is that it doesn’t manifest until after childbearing years, so the disease is passed on to the offspring. 4.

Which genetic disease is considered a monosomy condition and not a trisomy disease? a. Down syndrome b. Edward syndrome c. Turner syndrome d. Patau syndrome Answer: c. Turner syndrome is a monosomy disease with a female phenotype, while the rest of the disorder involves a trisomy disorder.

What happens in the case of a separation of the zygote at the two-cell stage? a. Dizygotic twins b. Fraternal twins c. Polar body formation d. Monozygotic twins Answer: d. Monozygotic twinning happens when cells of the zygote split early in the process after the zygote is formed. The earlier this happens the greater is the likelihood of the twins have different placentae.

At what week gestation are the products of conception referred to as an embryo? a. One week b. Two weeks c. Three weeks d. Four weeks Answer: c. Prior to three weeks gestation, the products of conception are not called an embryo; this is the pre-embryonic stage. The embryo is what the products of conception called between three and eight weeks gestation.

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What cells become the fetal part of the placenta? a. Morula cells b. Inner cell mass c. Trophoblast cells d. Blastomeres Answer: c. The cells of the trophoblast will become the fetal portion of the placenta, while the inner cell mass becomes the embryo.

What hormone secreted by the trophoblast will allow the corpus luteum in the female ovary to continue to thrive and support the pregnancy? a. Luteinizing hormone b. Progesterone c. Estrogen d. Human chorionic gonadotropin Answer: d. The trophoblast will allow the corpus luteum to continue to thrive and support the pregnancy by secreting human chorionic gonadotropin.

The mesodermal layer gives rise to all of the cells, excluding what structure in the embryo? a. Muscles b. Nerves c. Skeleton d. Heart Answer: b. The nerves come from the ectoderm and the rest of the structures (the muscles, skeleton, and heart) come from the mesoderm.

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What provides the surface area for the exchange of nutrients and wastes across the placenta in the fetal circulation? a. Amnion b. Umbilical cord 438

c. Trophoblast d. Chorionic villi Answer: d. The chorionic villi act as the main surface area for the exchange of nutrients and waste products across the placenta.

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COURSE SUMMARY This course was designed to appeal to the undergraduate interested in learning about human anatomy and physiology. Through the study of pictures, diagrams, and words, you have studied the entirety of the human body, from the cellular/microscopic levels, to the developmental levels, and finally to the macroscopic/anatomic levels of the human body. After talking about cells in general, each body system was discussed in turn so that, now that you are at the end of the course, you should feel more comfortable in any endeavor that requires thorough understanding of how the human body works. Chapter one looked at the basics of cellular anatomy and physiology. This included a study of the cell membrane, the cytoplasm of the cell, and the different organelles that can be found in the cell. The nucleus was examined as one of the more important organelles of the cell, containing the genetic information in the form of chromosomes and directing cellular functions. Also covered in this chapter was protein synthesis and the differentiation of cells. The topic of chapter two was the formation of body tissues and tissue types. While cells have many similarities, there are differences in structure and function. How cells make tissues was covered in this chapter as well as the structure and function of different tissue types, including epithelial, connective, muscle, and nerve tissues. The focus of chapter three was the integumentary system, or the skin. The skin is considered the largest organ of the body, covering most of the external surface of the body. There are several layers that make up the skin, which have different functions. In the dermis of the skin are many different accessory structures, which are microscopic in nature. The skin serves several different functions in the body, which were also examined. The skeletal or bony system was the topic of chapter four. The discussion started with the anatomy and physiology of bone cells and bone tissue. Then the axial skeleton (the skull, spine, and ribcage) was covered in detail as well as the appendicular skeleton (mainly the extremities). The function of joints and ligaments was discussed as they are important aspects of the skeletal system.

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The anatomy and physiology of the muscular system were the topics of chapter five. It began with a discussion of muscles and tendons as well as the different types of muscle tissue. The muscles of the head, neck, trunk, upper extremities, and lower extremities were also discussed. Chapter six examined the structure and function of the central nervous system. There are different types of brain cells—some of which conduct electricity and others that protect and support the electrically-active nerve cells. The gross anatomy and basic functions of the brain were covered in this chapter as well as the gross anatomy and basic functions of the spinal cord, which, as you have seen, is also a part of the CNS or central nervous system. Chapter seven in the course talked about the structure and function of the peripheral nervous system. These are the nerves located outside of the brain and spinal cord. The major somatic sensory and motor nerves were covered, including the way the major senses are picked up by the body. The cranial nerves, that do not come from the spinal cord, have unique functions, which were discussed. The structure and function of the autonomic nervous system were also covered. The focus of chapter eight was the endocrine system. This involved the hormones and their interactions with the various body systems. There are numerous endocrine organs both within the brain and outside in the rest of the body. The hypothalamus, the pituitary gland, and the pineal gland are all located near or within the brain. The other endocrine glands covered were the adrenal, the thyroid, the parathyroid glands, and the endocrine portion of the pancreas. The anatomy and physiology of the heart were discussed in chapter nine in the course. The heart acts as the major pump that forces blood through the rest of the body. The cells of the heart (cardiac muscle cells) have a unique electrical activity and synchronize the activity of the chambers of the heart. The coronary arteries are the major arteries supplying the heart; as you have seen, they are important because damage to any of these arteries can potentially cause a heart attack. The discussion of the cardiovascular system continued in chapter ten. There are arteries, veins, and capillaries that allow for blood flow and gas exchange in the tissues after oxygenated blood is pumped out of the heart and before deoxygenated blood reenters it. The components of

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blood and blood typing are also an important aspect of the cardiovascular system and were topics in this chapter. The lymphatic and immune system were covered together in chapter eleven. The lymphatic system includes the vessels of the lymphatic system that filter blood and pathogens, making these structures important to the immune system. The thymus gland is a part of the immune system as well as the spleen. Both of these were discussed in that chapter. The immune system is broadly divided into the innate and adaptive immune system. The cells of the immune system and the physiology of these aspects were also explained in detail in the chapter. The structure and function of the respiratory system were the main topics of chapter twelve. The respiratory system is broadly divided into the upper respiratory tract and the lower respiratory tract. The structures of the upper and lower respiratory tracts were discussed. As was the anatomy and physiology of the gas exchanging structures of the lungs (the alveoli). The topic of chapter thirteen was the human digestive system. It entails everything in the digestive process from the mouth to the anus as well as several other structures involved in digestion, including the liver, gallbladder, and the exocrine portion of the pancreas. The different anatomical structures included as part of the digestive system were covered in detail, including how they convert food into nutrients used by the body. Chapter fourteen was a continuation of the digestive system; however, it involved a discussion of the microscopic and molecular aspects of metabolic processes. Carbohydrate, protein, and lipid metabolism were discussed as well as the important energy-producing process of glucose metabolism. The overall physiology of human nutrition and nutritional needs in humans were also examined as part of this chapter. The topic of chapter fifteen was the urinary system. The urinary tract begins in the kidneys with urine traveling through the ureters, bladder, and urethra. The anatomy and physiology of the kidneys were discussed as well as the microscopic anatomy of these structures. Closely connected to the anatomy is the unique physiology of the kidneys. The creation of urine was also explained in detail in the last part of this chapter.

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Chapter sixteen i covered fluids, electrolytes, and the acid-base system. This included a discussion of the various fluid compartments in the body as well as how water and electrolytes are balanced by the somatic cells and renal system. Acid-base physiology depends on activities of both the lungs and the kidneys, which were also examined; there are several acid-base disorders that require compensation by both of these systems—also covered in the last part of the chapter. The male reproductive system was the topic of chapter seventeen. It included coverage of the anatomy of the male reproductive system as well as the physiology (including the male reproductive hormones) involved in this system. Finally, the embryological development of the male reproductive system was discussed. Chapter eighteen i examined the female reproductive system. First, the anatomy of the female reproductive system was covered, including the internal and external anatomic structures. The physiology of the menstrual cycle and female hormones were included in this chapter as well as the anatomy and physiology of the female breast. Finally, the embryologic development of the female reproductive system was also discussed. The focus of chapter nineteen was developmental anatomy and physiology. This included a discussion of genetics and how it applies to human phenotypes. Fertilization was more completely covered than it was in prior reproductive system chapters and the development of the embryo was explained in detail. As the embryo becomes a fetus at eight weeks gestation, the development continues; this was covered as the final topic of this chapter.

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COURSE QUESTIONS AND ANSWERS 1. Which cell membrane structure forms channels for ions to pass through? a. Phospholipid b. Peripheral protein c. Glycolipid d. Integral protein Answer: d. An integral protein will form a channel that allows hydrophilic (charged) ions to pass through. 2.

Which part of the cell membrane helps identify the cell as belonging to the self? a. Phospholipid b. Glycolipid c. Protein d. Cholesterol Answer: b. It is the glycolipid portion, or the carbohydrates on a cell membrane, that help identify the cell as belonging to the self. Glycoproteins and plain carbohydrates attached to the cell membrane will also do this.

Which organelle of the cell is most associated with the genetic material in the cell? a. Endoplasmic reticulum b. Mitochondrion c. Nucleus d. Nucleolus Answer: c. Almost all of the genetic material of the cell is located in the nucleus. A small part of it is located in the mitochondria.

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Which organelle helps make ribosomes involved in protein synthesis? a. Nucleolus b. Endoplasmic reticulum c. Golgi apparatus d. Peroxisome Answer: a. The nucleolus is responsible for making the ribosomes. It is located inside the nucleus and contributes to protein synthesis by sending the ribosomes to the rough endoplasmic reticulum for protein synthesis.

How many bases form a codon in the DNA sequence (in a gene)? a. two b. three c. four d. six Answer: b. A codon consists of three bases that are uniquely arranged. The different codons correlate with different amino acids that ultimately make a protein.

How many chromosomes are in nucleus of a human cell? a. 12 b. 23 c. 46 d. 64 Answer: c. There are twenty-three pairs, or a total of 46 chromosomes, in the human nucleus inside each of the cells.

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How many standard amino acids are coded for by the DNA molecule? a. 15 b. 20 c. 26 d. 46 Answer: b. There are twenty amino acids that are coded for by the codons in the DNA molecule.

Which base is not seen in the RNA molecule? a. Guanine b. Cytosine c. Thymine d. Adenine Answer: c. Thymine is replaced by uracil in the RNA molecule when the transcription process occurs and DNA is transcribed into the RNA sequence.

What is the most common post-translational modification that can happen to a proprotein to make an active protein? a. Phosphorylation b. Acetylation c. Cleavage d. Disulfide bonding Answer: a. Phosphorylation of a protein strand is the most common posttranslational modification that happens to a proprotein molecule before it can become a protein.

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10.

A cell that can differentiate into any type of human cell is called what? a. Hematopoietic b. Pluripotent c. Stem cell d. Totipotent Answer: d. A totipotent cell can differentiate into any cell type in the body. Only the human zygote and the first few daughter cells that come from it are truly totipotent. After the first few divisions, the cells become too differentiated and no longer totipotent.

11.

Which type of cell junction allows for an epithelial cell to connect to the basal lamina of the cell? a. Gap junctions b. Hemidesmosomes c. Desmosomes d. Zonula adherens Answer: b. The hemidesmosome is made from proteins that connect the base of the epithelial cell to the basal lamina “beneath” the cell.

12.

Which of the following is not considered connective tissue? a. Blood b. Bone c. Skin d. Cartilage Answer: c. Skin is not connective tissue; it is considered epithelial tissue.

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13.

Which type of epithelial tissue lines the alveoli of the lungs? a. Pseudostratified b. Stratified columnar c. Simple squamous d. Stratified squamous Answer: c. Simple squamous epithelium lines the alveoli of the lungs and assists with diffusion of materials from one place to another across the cells.

14.

What is the main function of transitional epithelial tissue? a. Stretching b. Protection c. Secretion d. Absorption Answer: a. Transitional epithelial tissue allows the urinary tract tissue to stretch and be flexible.

15.

Ciliated pseudostratified epithelium is not found in which of the following locations? a. Esophagus b. Trachea c. Nasal mucosa d. Bronchi Answer: a. Ciliated pseudostratified epithelium is referred to as respiratory epithelium because it is found in the trachea, nasal mucosa, and bronchial tree (bronchi).

16.

In which of the following areas would you find keratinized stratified epithelium? a. Lower esophagus b. Bladder c. Skin d. Vagina 448

Answer: c. The skin is the main area where this type of epithelium is located. 17.

Which of the following is not necessary to classify tissue as connective tissue? a. Water b. Fiber c. Cells d. Ground substance Answer: b. Each of these is a component of most connective tissue; however, blood is considered connective tissue despite not having any fiber or fibrous material.

18.

What protein compound gives lungs and blood vessels their ability to stretch and recoil? a. Type III collagen b. Proteoglycan c. Elastin d. Glycosaminoglycan Answer: c. Elastin is found in the lungs and blood vessels, which these tissues recoil and stretch.

19.

Which type of neuroglial cells are found only in the peripheral nervous system? a. Oligodendrocytes b. Schwann cells c. Astrocytes d. Microglial cells Answer: b. The Schwann cells are found mainly in the PNS, while the other cell types are neuroglia found mainly in the CNS.

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20.

Which of the following is the space between two nerve cells? a. Soma b. Dendrite c. Axon d. Synapse Answer: d. The synapse is the space between two nerve cells. It is also referred to as the synaptic cleft.

21.

Which skin layer is not considered to contain keratinocytes? a. Stratum granulosum b. Stratum basale c. Stratum lucidum d. Stratum spinosum Answer: b. Of all the layers of the skin, only the stratum basale is not considered to contain keratinocytes.

22.

What structures are dermal fold which increase the connection between the dermis and epidermis? a. Dermal papillae b. Meissner’s corpuscles c. Basal lamina d. Arrector pili Answer: a. The dermal papillae increases the connection between the dermis and epidermis by extending upwards from the deeper (dermal) layer to the more superficial (epidermal) layer.

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23.

Which cells in the skin make collagen and elastin? a. Langerhans cells b. Keratinocytes c. Merkel cells d. Fibroblasts Answer: d. Fibroblasts are cells within the dermis that make elastin and collagen.

24.

Which protein binds water in order to keep skin looking fresh and hydrated? a. Collagen b. Elastin c. Keratin d. Keratohyalin Answer: a. Collagen binds water in order to keep skin looking younger, refreshed, and hydrated.

25.

What is the collection of basal cells called that contribute to the growth of hair in the epidermis? a. Hair matrix b. Hair shaft c. Hair bulb d. Hair papilla Answer: a. It is the hair matrix that is made from basal cells and contributes to the formation of the hair shaft.

26.

Which part of the hair is the visible part of this structure? a. Hair matrix b. Hair shaft c. Hair bulb d. Hair papilla

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Answer: b. The hair shaft is what sticks up above the epidermis and is the visible part of the hair structure. 27.

What is another name for the nail cuticle? a. Hyponychium b. Nail bed c. Eponychium d. Lunula Answer: c. The eponychium is the medical term for the nail cuticle, which is located at the proximal aspect of the nail base.

28.

What structure is at the most distal aspect of the nail bed? a. Hyponychium b. Nail fold c. Eponychium d. Lunula Answer: a. The hyponychium is the most distal portion of the nail bed, just where the nail itself extends off the end of the fingertip or toe.

29.

What functions in the skin to dissipate heat during exercise or hot environments? a. The arterioles will constrict in the skin b. The arrector pili muscles contract c. The sweat glands secrete fluid d. The sebaceous glands secrete oil Answer: c. In a hot environment or during exercise, the sweat glands will secrete more sweat, which evaporates and causes loss of body heat, cooling the body.

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30.

Which functional change in skin does not happen as a person gets older? a. There is decreased keratin concentration in the epidermis b. The epidermis becomes thinner c. There is decreased elastin and collagen d. There is decreased sweating Answer: a. Each of these things occur as part of the aging process; however, the keratin concentration is not appreciably decreased in aged skin.

31.

From what area of the bone does growth occur? a. Red marrow b. Epiphyseal plate c. Diaphysis d. Metaphysis Answer: b. The bone marrow grows at the epiphyseal plate, which is not particularly active in adult long bones.

32.

What part of bone provides the nerve endings and blood supply to compact bone? a. Periosteum b. Articular cartilage c. Endosteum d. Epiphyseal line Answer: a. The periosteum supplies lymph vessels, blood vessels, and nerve endings to compact bone.

33.

Which bone cell type makes the mineral matrix of bony tissue? a. Osteoclast b. Osteoblast c. Osteogenic cell d. Osteocyte

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Answer: b. The osteoblast makes new bone by secreting minerals that form the bony matrix. These are the only bone cells that actually make new bone. 34.

What are the structures that house the different osteocytes within the bony tissue? a. Trabeculae b. Canaliculi c. Central canals d. Lacunae Answer: d. The lacunae are the spaces that house the osteocytes, connected to one another for cell-cell communication by canaliculi.

35.

Which bone is not a part of the axial skeleton? a. Mandible b. Sternum c. Sacrum d. Clavicle Answer: d. The clavicle is part of the shoulder girdle, making it a part of the appendicular skeleton rather than the axial skeleton.

36.

Which part of the face is also referred to as the “cheekbone”? a. Zygomatic arch b. Temporal bone c. Temporal fossa d. Infratemporal fossa Answer: a. The zygomatic arch forms the shape of the cheek and is referred to as the cheekbone even though it is part of two separate bones.

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37.

Which part of the vertebra is the process where it attaches to the vertebra beneath it? a. Transverse process b. Spinous process c. Superior articular process d. Inferior articular process Answer: d. The inferior articular process attaches the vertebra to the vertebra beneath it.

38.

Which is not a part of the sternum? a. Clavicle b. Manubrium c. Body d. Xyphoid Answer: a. The sternum consists of the manubrium, body, and xyphoid. The clavicle is a separate bone that attaches to the manubrium.

39.

Which projection forms the tip of the elbow? a. Olecranon process b. Trochlea c. Medial epicondyle d. Lateral epicondyle Answer: a. The prominent olecranon process forms the tip of the elbow.

40.

Which structure connects the two pubis portions of the pelvis anteriorly? a. Acetabulum b. Pubic symphysis c. Sacroiliac joint d. Superior pubic ramus

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Answer: b. The pubic symphysis is a non-moveable joint that connects the pubis portions of the pelvis in the anterior part of the pelvis. 41.

Which structure in the muscle cell stores and releases calcium ions in order to allow for muscle contraction? a. Sarcolemma b. Sarcomere c. Sarcoplasm d. Sarcoplasmic reticulum Answer: d. The sarcoplasmic reticulum or SR stores and releases calcium ions that participate in the contraction of muscle fibers.

42.

Which structure in a muscle is considered the smallest? a. Myofibril b. Sarcomere c. Fascicle d. Muscle fiber Answer: b. The sarcomere is the smallest unit and is the functional unit in the muscle cell. It consists of an actin protein, a myosin protein, plus regulatory proteins.

43.

Which ion is released by the sarcoplasmic reticulum that causes muscle cells to contract? a. Potassium b. Sodium c. Magnesium d. Calcium Answer: d. When calcium is released by the SR, it triggers the actin fibers to move past the myosin fibers, causing a muscle cell to contract.

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44.

Which of the following would be defined as the prime mover of a limb action, such as flexion? a. Synergist b. Antagonist c. Agonist d. Fixator Answer: c. The agonist is the prime mover of a particular joint action. The synergist can help or act as a fixator, while the antagonist opposes the agonist muscle.

45.

Which is the major muscle that rotates and laterally flexes the head? a. Semispinalis muscle b. Splenius capitis muscle c. Longissimus capitis muscle d. Sternocleidomastoid muscle Answer: d. The sternocleidomastoid muscle is the main mover of the head, rotating the head and laterally flexing it.

46.

Which is not considered a posterior or back muscle? a. Middle scalene b. Splenius cervicis c. Omohyoid d. Semispinalis capitis Answer: c. Each of these are posterior back or neck muscles except for the omohyoid, which is a muscle in the anterior neck.

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47.

Which is not a typical pelvic floor muscle? a. Pubococcygeus b. Iliococcygeus c. Urethrovaginalis d. Ischiococcygeus Answer: c. These are muscles of the pelvic floor except for the urethrovaginalis muscle, which is located in the female vagina.

48.

Which shoulder-stabilizing muscle of the pelvic girdle is considered an anterior muscle on the thorax? a. Rhomboid major b. Trapezius c. Rhomboid minor d. Pectoralis minor Answer: d. Each of these is a shoulder-stabilizing muscle of the pelvic girdle. Each of these is a posterior muscle, while the pectoralis minor is an anterior muscle.

49.

Which muscles in the thigh do not act to extend or abduct the femur? a. Tensor fascia lata b. Gluteus maximus c. Gluteus minimis d. Gluteus medius Answer: a. Each of these are gluteal muscles; however, while most of them extend and abduct the femur, the tensor fascia lata flexes and abducts the thigh.

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50.

Which thigh muscle is not located in the anterior compartment of the thigh? a. Sartorius b. Vastus medialis c. Vastus lateralis d. Adductor longus Answer: d. The medial compartment contains the adductor longus, while the rest of the muscles are located in the anterior compartment of the thigh.

51.

What are the gaps between myelin covering the axon called? a. Nodes of Ranvier b. Axon segments c. Axoplasm d. Axon hillocks Answer: a. Nodes of Ranvier are spaces or gaps in the axon that do not contain myelin and divide the neuron’s axon into axon segments.

52.

What type of axon is least commonly seen in the human CNS? a. Anaxonic axon b. Bipolar axon c. Multipolar axon d. Unipolar axon Answer: d. Unipolar axons are rare in humans and primarily seen in invertebrates.

53.

The act of sodium ions changing the membrane potential in nerve cells from -70 mV to +30 mV is called what? a. Repolarization b. Resting membrane potential c. Action potential d. Depolarization 459

Answer: d. The process of going from a negative to positive net membrane potential is referred to as depolarization. The reverse of this happens via potassium ions and is called repolarization. 54.

What starts the action potential in a nerve cell? a. Sodium is pumped out of the cell b. Sodium channels open and sodium flows inside of the cell c. Potassium is pumped into the cell d. Potassium channels open and potassium flows outside of the cell Answer: b. The sodium channels open and sodium flows inside of the cell, causing the action potential to occur.

55.

What structure makes up the largest part of the brain? a. Cerebrum b. Cerebellum c. Diencephalon d. Brainstem Answer: a. The cerebrum is the main “thinking” part of the brain and is the largest part by mass in the central nervous system.

56.

What is the ridge seen on the surface of the cerebrum called? a. Sulcus b. Cortex c. Gyrus d. Nucleus Answer: c. The gyrus is the ridge seen on the surface of the cerebral cortex, with the sulcus being the space or cleft between the gyrus.

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57.

Which sensation does not go through the thalamus in order to reach the cerebral cortex? a. Olfaction b. Vision c. Hearing d. Touch Answer: a. Only olfaction goes directly from the periphery to the cerebral cortex, bypassing the thalamus.

58.

Which part of the brainstem is mainly concerned with sleep and wakefulness? a. Pons b. Tectum c. Reticular formation d. Tegmentum Answer: c. The reticular formation in the medulla is involved in sleep and wakefulness.

59.

What meningeal layer lies closest to the brain tissue? a. Pia mater b. Arachnoid trabeculae c. Arachnoid mater d. Dura mater Answer: a. The pia mater is the layer of the meninges that is closest to the brain tissue. In fact, it cannot be physically separated from the brain itself.

60.

Where is the cauda equina located in the nervous system? a. Between the two halves of the cerebrum b. In the ventricular system of the brain c. At the base of the brainstem d. Below the spinal cord 461

Answer: d. The cauda equina represents the distal spinal nerves that extend below the spinal cord; it is given its name because it looks like a horse’s tail. 61.

Which ganglion type is not associated with the sympathetic nervous system? a. Prevertebral ganglia b. Paravertebral ganglia c. Chain ganglia d. Dorsal root ganglia Answer: d. Each of these ganglion types are affiliated with the sympathetic nervous system except for the dorsal root ganglia, which are sensory in nature and associated with the somatic nervous system.

62.

Which nerve plexus is not associated with the autonomic nervous system? a. Gastric plexus b. Enteric plexus c. Lumbar plexus d. Esophageal plexus Answer: c. Each of these plexuses is linked to the autonomic nervous system and is found in the walls of the various gastrointestinal organs, except for the lumbar plexus, which is associated with the somatic nervous system.

63.

Which cranial nerve is considered the first cranial nerve or cranial nerve I? a. Olfactory b. Optic c. Oculomotor d. Abducens Answer: a. The olfactory nerve controls the sense of smell and is the first cranial nerve.

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64.

Which cranial nerve supplies most muscles of the face? a. Trigeminal b. Facial c. Abducens d. Oculomotor Answer: b. The facial nerve supplies motor abilities to the muscles of facial expression. The muscles of mastication are controlled by the trigeminal nerve.

65.

The ventral nerve root of the spinal nerve contains what kinds of fibers? a. Motor and autonomic b. Sensory and motor c. Motor only d. Sensory only Answer: a. The ventral nerve root exits the spinal cord and contains both motor and autonomic nerve fibers.

66.

Which nerve plexus gives rise to the sciatic nerve? a. Cervical b. Brachial c. Lumbar d. Sacral Answer: d. The sacral plexus gives rise to the sciatic nerve. It is made from the lower lumbar and sacral nerve roots.

67.

The sensation of umami is picked up when the taste bud perceives what molecule? a. Alkaloid b. L-glutamate c. Sodium d. Glucose

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Answer: b. Each of these are molecules that detect taste sensations, with Lglutamate being the molecule that allows for the perception of umami. 68.

Which sensation is most associated with the cribriform plate? a. Taste b. Light touch c. Hearing d. Smell Answer: d. The sense of smell involves nerve fibers from the upper nasal cavity that travel through the cribriform plate in the ethmoid bone, leading to the brain and causing the sense of smell.

69.

Which eye structure is considered part of the outer layer of the eyeball? a. Choroid b. Sclera c. Ciliary body d. Iris Answer: b. Each of these is an area of the middle layer of the eye except for the sclera, which is located in the outer layer of the eyeball.

70.

Where do the sensory nerves from the dorsal column decussate (cross over) in the nervous system so that the opposite side of the brain controls the sensory aspects of the other side of the body? a. Medulla b. Pons c. Spinal cord d. Thalamus Answer: a. The decussation process happens in the medulla, just after the first sensory nerves end and the second sensory nerve begins.

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71.

Which hormone stimulates the maturation of the gametes in the reproductive system of males and females? a. FSH b. LH c. GH d. TSH Answer: a. FSH or follicle stimulating hormone causes the maturation of the gametes (sperm and egg) in both males and females. It is made by the anterior pituitary gland.

72.

Which hormone regulates sleep and is secreted by the pineal gland? a. Oxytocin b. Melatonin c. Norepinephrine d. Cortisol Answer: b. Melatonin regulates the sleep cycle and is secreted by the pineal gland.

73.

Which hormone has an intracellular receptor because it can pass through the cell membrane and act on the cell directly? a. Cortisol b. FSH c. GH d. Norepinephrine Answer: a. Because cortisol is a steroid hormone, it will pass through the cell membrane and affect an intracellular receptor. The others have extracellular receptors.

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74.

Which is the most common second messenger in the activation of the target cell when hydrophilic hormones act on the cell? a. Diacylglycerol b. Cyclic AMP c. Calcium ions d. Inositol triphosphate Answer: b. Cyclic AMP is the most common second messenger, which activates intracellular processes once it is created by the binding of a hydrophilic hormone to an intramembranous receptor.

75.

Which structure makes somatostatin or GHIH? a. Pars intermedia b. Posterior pituitary c. Hypothalamus d. Pars distalis Answer: c. The hypothalamus secretes somatostatin or GHIH in order to inhibit the release of somatotropin, also called growth hormone.

76.

Which hormone is responsible for the let-down reflex in breastfeeding? a. Dopamine b. Prolactin c. Gonadotropin releasing hormone d. Oxytocin Answer: d. Oxytocin causes the let-down reflex in breastfeeding, while prolactin aids in milk gland production and the secretion of milk in breastfeeding.

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77.

What is not an effect of aldosterone? a. Increases blood pressure b. Increases potassium c. Increases sodium d. Increases blood volume Answer: b. Aldosterone will cause increases in all of these things except for the potassium level, which will decrease under the influence of this hormone.

78.

As a result of output of the chromaffin cells of the adrenal gland, which body system change is most likely to occur? a. Increased blood pressure b. Pupillary constriction c. Decreased glucose levels d. Increased immune function Answer: a. The output of the chromaffin cells is epinephrine and norepinephrine, which results in multiple bodily changes, including increased blood pressure. The rest of the choices do not happen as a result of these hormones.

79.

Which gland contributes most to the homeostasis of calcium in the bloodstream? a. Adrenal glands b. Parathyroid glands c. Thyroid gland d. Pituitary gland Answer: b. The parathyroid glands produce parathyroid hormone, which regulates the calcium level in the bloodstream.

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80.

Which hormone is secreted by the delta cells of the pancreatic islets? a. Somatostatin b. Insulin c. Glucagon d. Pancreatic polypeptide Answer: a. The delta cells make somatostatin, which is the same hormone made by the hypothalamus, the stomach, and the intestines.

81.

Which part of the pericardial sac is the same as the wall of the heart? a. Epicardium b. Fibrous pericardium c. Parietal pericardium d. Serous pericardium Answer: a. The epicardium is the part of the serous pericardium, a more delicate layer than the fibrous pericardium, that is the same as the wall of the heart.

82.

Which sulcus is located between the atria and ventricles of the heart? a. Coronary sulcus b. Auricular sulcus c. Anterior interventricular sulcus d. Posterior interventricular sulcus Answer: a. The coronary sulcus is a deep groove located between the atria and ventricles and the interventricular sulci (anterior and posterior) are located between the ventricles.

83.

What is the valve called that separates the right atrium from the right ventricle? a. Aortic valve b. Tricuspid valve c. Mitral valve d. Pulmonic valve 468

Answer: b. The tricuspid valve separates the right atrium from the right ventricle. It is located in the atrioventricular membrane and is supported by the cardiac skeleton. 84.

What is the valve called that separates the left atrium and the left ventricle? a. Aortic valve b. Tricuspid valve c. Mitral valve d. Pulmonic valve Answer: c. The mitral valve separates the left atrium from the left ventricle. It closes during systole to prevent backflow of blood back into the left atrium.

85.

What is the pacemaker of the heart? a. AV node b. Bundle of His c. SA node d. Purkinje fibers Answer: c. The SA node has the fastest rate of depolarization and is considered the pacemaker of the heart. It is located in the right atrium.

86.

Where does the cardiac impulse go after it leaves the AV node? a. Left bundle branch b. Bundle of His c. SA node d. Purkinje fibers Answer: b. The next place the cardiac impulse goes after leaving the AV node is the bundle of His, which spreads down the interventricular septum.

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87.

What is represented by the QRS complex on an ECG? a. Depolarization of the atria b. Repolarization of the atria c. Depolarization of the ventricles d. Repolarization of the ventricles Answer: c. The QRS complex is the electrical activity that represents the depolarization of the ventricles. It is larger than the other inflections because the ventricles are large.

88.

About when do the ventricles begin to contract in the cardiac electrical cycle? a. At the peak of the P wave b. At the peak of the R wave c. At the end of the T wave d. At the end of the S wave Answer: b. The peak of the R wave is when the ventricles begin to contract. This is halfway through the ventricular depolarization phase (the QRS complex).

89.

What is the potential of the heart pump out more blood during exercise called? a. Ejection fraction b. Cardiac output c. Cardiac reserve d. Heart rate Answer: c. The cardiac reserve is the potential of the heart to pump out more blood or its “reserve” for exercise.

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90.

What heart rate would there be in the heart if there was no parasympathetic tone applied to the heart? a. 60 bpm b. 80 bpm c. 100 bpm d. 120 bpm Answer: c. The sympathetic tone only applied to the heart with no parasympathetic input will lead to a heart rate of 100 bpm.

91.

Which cell type does not come from a myeloid stem cell? a. RBC b. Platelets c. T cells d. Eosinophils Answer: c. T cells are lymphocytes that come from the lymphoid cell line and not the myeloid cell line. The others all come from myeloid stem cells.

92.

Which blood cell type matures outside of the bone marrow? a. Platelets b. B cells c. Basophils d. T cells Answer: d. T cells will mature in the thymus and not in the bone marrow. The others will mature within the confines of the bone marrow.

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93.

What molecule is least likely to be necessary for the synthesis of hemoglobin and the making of red blood cells? a. Zinc b. Magnesium c. Copper d. Iron Answer: b. Each of these minerals is necessary in the making of hemoglobin and RBCs; however, magnesium is not part of these processes.

94.

What is the process called that involves the attraction of WBCs to sites in the tissues where they are necessary? a. Diapedesis b. Emigration c. Cellular differentiation d. Chemotaxis Answer: d. Chemotaxis involves the signaling and attraction of WBCs so they can go to the sites where they are necessary.

95.

What formed element in blood is most involved with blood clotting? a. Monocytes b. T lymphocytes c. Platelets d. Neutrophils Answer: c. Platelets are specifically responsible for the clotting of blood, acting to cause the initial clot after a break in a blood vessel has happened.

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What vitamin is most crucial to the blood clotting process in humans? a. Vitamin K b. Vitamin E c. Vitamin C d. Vitamin B12 Answer: a. Many clotting factors depend particularly on vitamin K in order to be synthesized. A deficiency of vitamin K can result in bleeding complications.

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The pulmonary circuit consists of several vessels. Which blood vessel is most likely to contain oxygenated blood? a. Pulmonary trunk b. Right pulmonary artery c. Pulmonary arterioles d. Pulmonary veins Answer: d. The pulmonary veins contain oxygenated blood that has been oxygenated by the exchange between the alveoli and the pulmonary capillaries. The other vessels listed contain deoxygenated blood.

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The descending aorta ends in the abdomen by turning the aorta into what? a. The common iliac arteries b. The femoral arteries c. The aortic arch d. The superior mesenteric artery Answer: a. The descending aorta ends in the lower abdomen by dividing into the common iliac arteries (one on each side of the body).

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What artery sends branches to supply blood to each lower limb? a. Peroneal artery b. External iliac artery c. Internal iliac artery d. Median sacral artery Answer: b. The external iliac artery sends nearly all of its branches to each lower limb. The internal iliac artery supplies mainly the pelvic organs and genitalia.

100. Which artery is a continuation of the axillary artery in the upper arm? a. Thoracic artery b. Brachial artery c. Radial artery d. Ulnar artery Answer: b. The brachial artery is the continuation of the axillary artery in the upper arm. This artery comes from the thoracic artery. Branches of the brachial artery include the radial and ulnar arteries in the forearm. 101. What is least likely to be carried in the lymphatic vessels? a. Dietary fatty acids b. Immune cells c. Erythrocytes d. Fat-soluble vitamins Answer: c. Each of these are carried by the lymphatic vessels as they travel throughout the body; however, erythrocytes are not commonly carried through these vessels.

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102. In the lymphatic system, where are lacteals located? a. In the small intestine b. Around the heart c. In lymph nodes d. In the liver Answer: a. The lacteals are located in the area of the small intestine, where they pick up dietary fatty acids, other lipids, and lipid-soluble vitamins, sending them to the liver. 103. What is the initial defense against pathogens in the immune system? a. B cell system b. Barrier mechanisms c. Innate immunity d. T cell system Answer: b. Barrier mechanisms are the first defense against pathogens and attempt to stop them from entering the body in the first place. 104. What type of cell is also referred to as a “plasma cell”? a. B lymphocyte b. T lymphocyte c. Natural killer cell d. Cytotoxic cell Answer: a. A B lymphocyte cell that is actively secreting antibodies is referred to as a plasma cell.

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105. Which is not considered a secondary lymphoid organ? a. Spleen b. Thymus c. Lymphoid nodules d. Lymph nodes Answer: b. Each of these is a secondary lymphoid organ; however, the thymus gland is a primary lymphoid organ, which is involved in the initial maturation of lymphocytes. 106. What is the place where lymph fluid enters a lymph node called? a. Efferent vessel b. Germinal center c. Subcapsular sinus d. Afferent vessel Answer: d. The afferent vessel is the vessel leading into the lymph node, containing fluid to be filtered by the lymph node. 107. What are macrophages residing in connective tissue called? a. Histiocytes b. Kupffer cells c. Alveolar macrophages d. Dendritic cells Answer: a. Connective tissue macrophages are referred to as histiocytes. They act within the tissues to eliminate pathogens that enter connective tissue. 108. What is not a way that NK cells act to cause apoptosis in infected cells? a. By expressing the Fas ligand that binds to infected cells b. By releasing pore-forming perforins c. By attracting cytotoxic T lymphocytes d. By releasing protein-digesting enzymes 476

Answer: c. Each of these are ways that NK cells cause apoptosis except they don’t attract cytotoxic T lymphocytes to the infected cells. 109. Which T cell type in the immune system will express the CD8 molecule on its surface? a. Th1 cell b. Th2 cell c. Tc cell d. Treg cell Answer: c. The Tc cell or cytotoxic T cell is the only T cell that expresses the CD8 molecule on its surface. The other cell types will only express the CD4 molecule on their surfaces. 110. What is apoptosis? a. Binding of an antigen to an antibody b. Programmed cell death c. The same as phagocytizing a cell d. The presentation of an antigen on a professional antigen presenting cell Answer: b. Apoptosis is programmed cell death. In the immune system, it involves sending a signal to an infected cell or a cell that has not been selected to make antibodies that initiates cell death. 111. What is the purpose of the goblet cells in the respiratory tract? a. They produce mucus b. They have cilia that propel bacteria out of the respiratory tract c. They humidify the air d. They are involved in olfaction Answer: a. The goblet cells will produce the mucus that traps debris in the respiratory tract.

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112. Which sinus is located in the facial or “cheek” bones? a. Ethmoid sinus b. Maxillary sinus c. Frontal sinus d. Sphenoidal sinus Answer: b. The sinuses are named for the bone in which they reside. The maxillary sinus is located in the maxilla or cheek bone. 113. In the larynx is composed of different types of cartilage. Which cartilage is the most prominent? a. Arytenoid b. Thyroid c. Cricoid d. Corniculate Answer: b. The thyroid cartilage is the largest of the cartilages in the larynx. It is unpaired and located in the anterior portion of the larynx. 114. The place in the chest where the mainstem bronchi pass into the lungs along with the vessels and nerves is called what? a. Carina b. Bronchiole c. Alveolus d. Hilum Answer: d. The hilum is the part of the respiratory tract where the mainstem bronchi, the vessels, and the nerves enter the lungs.

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115. What is true of the different lobes of the lungs? a. There are two on each side of the body. b. There are three on each side of the body. c. There are two lobes on the right and three lobes on the left. d. There are two lobes on the left and three lobes on the right. Answer: d. The left lung consists of two lobes and the right lung consists of three lobes. The left lung has a smaller volume because of the room needed for the heart. 116. The smallest subdivision in the lung tissue is called what? a. Alveolus b. Pulmonary lobe c. Bronchopulmonary segment d. Pulmonary lobule Answer: a. As to size, the lobes are the largest, the bronchopulmonary segment is the next smallest, the pulmonary lobule is the next smallest, with the alveolus being the smallest subdivision. 117. In looking at the air pressure in the atmosphere and the lungs, which air pressure is considered the lowest? a. Air pressure in the atmosphere b. Air pressure in the intrapleural space c. Air pressure in the alveoli at full inspiration d. Air pressure in the lungs at full expiration Answer: b. The air pressure in the intrapleural space is always going to be less than the others as it is only about -4 mm Hg, which keeps the lungs adherent to the chest wall (along with the action of the fluid secreted in the pleural space).

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118. Which area of the brain has the least control over the act of breathing? a. Pons b. Hypothalamus c. Medulla d. Cerebellum Answer: d. The pons and medulla have respiratory breathing centers that help control breathing. The hypothalamus will participate by monitoring emotions related to breathing and the body temperature, which affect breathing. 119. What is the process by which the oxygen and CO2 leave their respective places in the tissues and move across the cell membrane? a. There is an ATP-dependent oxygen transporter and CO2 moves across via osmosis. b. There is a pore in the cell membrane where a molecule of O2 is exchanged for a molecule of CO2. c. The CO2 is transported via an intramembranous transporter and the oxygen diffuses across the membrane. d. Both CO2 and O2 travel across a pressure gradient via simple diffusion from a high pressure to a low pressure. Answer: d. Simple diffusion is what transports the CO2 and O2 across the cell membrane from a place of high pressure to a place of low pressure. 120. How many oxygen-binding heme molecules are there in a hemoglobin molecule? a. two b. four c. six d. eight

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Answer: b. There are four molecules of heme that help make up the hemoglobin molecule so that a total of four molecules of oxygen can bind to the hemoglobin protein. 121. Which nervous system input will be responsible for regulating the force and timing of the muscularis layer in the GI tract? a. Parasympathetic external input b. Sympathetic external input c. Myenteric plexus intrinsic input d. Submucosal plexus intrinsic input Answer: c. The myenteric plexus or plexus or Auerbach controls the force and timing of the muscularis layer as part of the enteric nervous system. 122. Which is a place where chemical digestion does not occur? a. Mouth b. Large intestine c. Small intestine d. Stomach Answer: b. Chemical digestion occurs in each of these places except for the large intestine. 123. Which enzyme is made in the saliva in order to start the enzymatic breakdown of carbohydrates? a. Lingual lipase b. Pepsin c. Salivary amylase d. Lysozyme Answer: c. Of these, only lingual lipase, salivary amylase, and lysozyme are secreted in the mouth. It is salivary amylase that aids in the digestive process of carbohydrates.

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124. Which is considered the hardest layer of the tooth? a. Cementum b. Enamel c. Dentin d. Root Answer: b. The hardest layer of the tooth is the enamel layer. It is the hardest substance in the body and overlies all the other layers of the tooth. 125. Which cells of the mucosa of the stomach secrete pepsinogen, which then gets turned into the active enzyme called pepsin? a. Enteroendocrine cells b. Parietal cells c. Mucus neck cells d. Chief cells Answer: d. The chief cells make pepsinogen that uses and requires HCl in order to make the active enzyme pepsin. 126. Which stomach hormone will actually slow absorption, motility, and gastric emptying? a. Gastrin b. Histamine c. Somatostatin d. Ghrelin Answer: c. Somatostatin actually decreases the gastric activity. It is under sympathetic control and will slow absorption, decrease motility, and lessen gastric emptying.

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127. In which part of the alimentary canal will you find the ampulla of Vater? a. Stomach b. Colon c. Jejunum d. Duodenum Answer: d. The ampulla of Vater opens into the duodenum, which is the opening of the bile and pancreatic ducts, allowing bile and pancreatic enzymes to be released into the lumen for digestive purposes. 128. What are the projections from the small intestine’s absorptive cell membranes that facilitate absorption called? a. Microvilli b. Villi c. Circular folds d. Crypts of Lieberkühn Answer: a. The microvilli cannot be seen by the naked eye as they are projections from the absorptive surface’s cell membranes that participate in absorption. 129. Which is not a vitamin synthesized by the bacteria in the large intestine? a. Cyanocobalamin b. Vitamin K c. Biotin d. Pantothenic acid Answer: a. Each of these is a vitamin that is made by the commensal bacteria in the large intestine except for cyanocobalamin, which is not made by bacterial sources.

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130. Which enzyme is made in the intestinal brush border for the activation of pancreatic enzymes in the duodenal lumen? a. Trypsin b. Chymotrypsin c. Carboxypeptidase d. Enteropeptidase Answer: d. It is enteropeptidase, made in the intestinal brush border, that activates trypsinogen to make trypsin, which further activates the rest of the pancreatic enzymes. 131. Which of the following carbohydrates is a monosaccharide? a. Sucrose b. Maltose c. Galactose d. Lactose Answer: c. These are mainly disaccharides but galactose is considered a monosaccharide. This means that it can be absorbed directly in the digestive tract and doesn’t have to be broken down any further through enzymatic actions. 132. When nucleic acids get digested, some of the products of digestion can be absorbed by the GI tract. Which breakdown product of nucleic acids cannot be absorbed by the enterocytes? a. Phosphate b. Nitrogenous bases c. Pentoses d. Nucleotides

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Answer: d. These products can all be absorbed easily in the small intestine, except for nucleotides, which need to be broken down further by enzymes before absorption can take place. 133. Which vitamin must have intrinsic factor to be absorbed, and is absorbed mainly in the terminal ileum? a. Folate b. Vitamin B12 c. Vitamin D d. Biotin Answer: b. Vitamin B12 or cyanocobalamin is a large molecule that gets absorbed only through combining with intrinsic factor and binding to a receptor. The combined intrinsic factor-B12 complex gets absorbed via endocytosis. 134. When it comes to energy production, what is considered the main energy source for making ATP in the human body? a. Triglycerides b. Amino acids c. Cholesterol d. Glucose Answer: d. Most energy reactions in the body come from the metabolism of glucose, which is the main energy source in the body. 135. Which of the following hormones is considered anabolic versus catabolic? a. Cortisol b. Glucagon c. Epinephrine d. Growth hormone

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Answer: d. Growth hormone is an anabolic hormone that causes the buildup of cells and tissues. The other hormones are catabolic, causing the breakdown of molecules. 136. From which of the following nutrients is the most energy or ATP obtained for the body? a. Proteins b. Nucleic acids c. Carbohydrates d. Lipids Answer: c. Carbohydrates and mainly glucose make the most energy for the body in reactions that break down glucose to make carbon dioxide, water, and energy. 137. What is the final electron receptor in anaerobic respiration? a. Pyruvate b. Glucose c. Lactic acid d. NADH Answer: c. Lactic acid is the final electron receptor in anaerobic respiration. It will generate an ATP molecule but it tends to build up in muscle tissue (although most of it ends up in the liver); it is believed to be why muscles get sore after anaerobic exercise. 138. Which part of the glucose metabolic process directly requires oxygen? a. Glycolysis b. Krebs cycle c. Anaerobic respiration d. Electron transport chain

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Answer: d. The electron transport chain requires oxygen, which serves as the final electron acceptor, combining with hydrogen ions to make water. 139. The metabolism of what nutrient leads to the development of urea? a. Fatty acids b. Carbohydrates c. Nucleic acids d. Amino acids Answer: d. When amino acids get broken down, they make ammonium ions, which must be further metabolized to make urea and water out of the ammonium ion plus CO2. 140. When the body is in starvation mode, what is the highest metabolic priority? a. To save protein for body processes. b. To have glucose available for fuel. c. To make ketone bodies for metabolism. d. To preserve nucleic acid synthesis. Answer: b. The priority in starvation is to have glucose available for fuel that is necessary for many processes, including brain function. 141. The micturition reflex involves a spinal reflex and what other aspects of the nervous system? a. Autonomic parasympathetic fibers b. Systemic motor fibers c. Systemic sensory fibers d. Autonomic sympathetic fibers Answer: a. The micturition reflex is mainly a parasympathetic nervous system reflex involving stretch receptors and a parasympathetic response to the bladder muscle, called the detrusor muscle.

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142. There are three types of epithelial linings in the male urethra. Which epithelial type is not present? a. Stratified squamous epithelium b. Transitional epithelium c. Pseudostratified squamous epithelium d. Simple cuboidal epithelium Answer: d. Each of these is a type of epithelium of the male urethra, except for simple cuboidal epithelium. 143. Which of the following does not offer protection for the kidneys? a. Renal capsule b. Adrenal glands c. Lower ribs d. Renal fat pads Answer: b. The adrenal glands sit atop the kidneys but do not participate in the actual protection of the kidneys. The others will participate in the protection of the kidneys from external trauma. 144. What is the part of the kidney that excretes the urine? a. The renal papillae b. The renal cortex c. The renal calyces d. The renal columns Answer: c. The renal calyces are the kidney structures that excrete urine into the pelvis of the kidneys.

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145. What is not a major function of the nephron of the kidneys? a. Toxin detoxification b. Blood filtration c. Reabsorption of water d. Excretion or secretion of urine Answer: a. The nephron itself does not participate in detoxification; it only filters blood, reabsorbs water and ions, and secretes/excretes urine. 146. What type of cell forms the visceral layer of the Bowman’s capsule? a. Simple squamous epithelium b. Pseudostratified columnar epithelium c. Podocyte layer d. Stratified squamous cells Answer: c. The visceral layer of the Bowman’s capsule consists of podocytes, which have pedicles or finger-like extensions and which are where filtration occurs. 147. The renin-angiotensin system is a complex system that affects blood pressure by constricting blood vessels (raising the blood pressure). What is the true vasoconstrictor molecule involved in this system? a. Angiotensin II b. Angiotensin I c. Renin d. Angiotensinogen Answer: a. In this system, the end product is angiotensin II, which is a potent vasoconstrictor in the body, causing an increase in blood pressure.

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148. Which part of the kidneys have aquaporin channel proteins that allow water to enter the vasa recta and prevent water absorption? a. Glomerulus b. Collecting ducts c. Proximal convoluted tubule d. Loop of Henle Answer: b. The collecting ducts have the “final say” in how much water leaves the kidneys. When activated by antidiuretic hormone, they have aquaporin channel proteins that remove water from urine to increase the water in the bloodstream. 149. Obligatory water reabsorption happens in the proximal convoluted tubule of the kidneys. What ion is responsible for this obligatory reabsorption of water? a. Sodium b. Potassium c. Bicarbonate d. Ammonium Answer: a. Water necessarily follows sodium, particularly in the proximal convoluted tubule. This means it passively diffuses along with the active transport of sodium. 150. Where in the kidneys are most of the ions and water reabsorbed? a. Collecting ducts b. Loop of Henle c. Proximal convoluted tubule d. Distal convoluted tubule Answer: c. The proximal convoluted tubule absorbs most of the ions and water that is initially filtered by the glomerulus.

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151. What is the major solute that is different between the plasma and the interstitial fluid or IF? a. Sodium b. Chloride c. Bicarbonate d. Protein Answer: d. There are similar concentrations of solutes in the IF and the plasma but the protein concentration is much different, with IF containing little protein and plasma containing a lot of protein. 152. Which ion is not much higher in intracellular versus extracellular fluid? a. Potassium b. Magnesium c. Chloride d. Phosphorus Answer: c. These are all much higher in concentration in the ICF when compared to the ECF, except for chloride, which is actually higher in the ECF. 153. When it comes to fluid losses in the body, from where is the most fluid lost in any given day? a. GI tract b. Sweat c. Urine d. Respiratory tract Answer: c. Most of the fluid lost is lvia the urinary tract, although each of these mechanisms account for some fluid losses.

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154. Where are the osmoreceptors in the body located that increase the sense of thirst? a. Salivary glands b. Carotid arteries c. Pituitary gland d. Hypothalamus Answer: d. The hypothalamus has osmoreceptors that are part of the thirst center, which detects the osmolality of plasma. 155. What cation is the major cation in the cell? a. Magnesium b. Calcium c. Potassium d. Sodium Answer: c. Through the action of the sodium-potassium pump, potassium is the most common cation seen in the intracellular space. 156. Which ion contributes most to the osmotic pressure within the blood plasma? a. Calcium b. Bicarbonate c. Potassium d. Sodium Answer: d. Sodium is the ion that contributes most to the osmotic pressure within the blood plasma because of its high concentration in this fluid space. 157. Which ion is co-regulated along the same processes as calcium in the body? a. Bicarbonate b. Phosphorus c. Chloride d. Potassium

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Answer: b. The regulation of the calcium and phosphorus levels happens through the same mechanisms in the body. 158. What is not considered a major buffering system in the body? a. Bicarbonate buffering system b. Phosphate buffering system c. Protein buffering system d. Nitrate buffering system Answer: d. Each of these is a major buffering system within the body except for nitrate, which isn’t considered a major buffering component in living things. 159. What disease process does not cause a reduction in the serum bicarbonate level? a. Addison’s disease b. Diabetic ketoacidosis c. Interstitial lung disease d. Diarrhea Answer: c. For various reasons, there will be a reduction in bicarbonate levels in each of these diseases except for interstitial lung disease. Addison’s disease involves low aldosterone levels; ketoacidosis involves the binding of bicarbonate by ketone bodies in the filtrate; and diarrhea will cause a loss of bicarbonate via the GI tract. 160. What is the effect of excess ketones in the bloodstream? a. Metabolic acidosis b. Metabolic alkalosis c. Respiratory acidosis d. Respiratory alkalosis Answer: a. Ketones will bind to bicarbonate in the filtrate and will cause a loss of bicarbonate in the bloodstream and resultant metabolic ketoacidosis.

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161. What is the tissue layer that is closest to the testis itself? a. Tunica albuginea b. Visceral tunica vaginalis c. Parietal tunica vaginalis d. Cremaster layer Answer: a. Each of these covers the testis; however, the innermost layer is the tunica albuginea, which is dense and intimately covers the testis, forming septa within it that separate the testis into hundreds of lobules. 162. Where in the testis does the sperm cell originate? a. Rete testes b. Epididymis c. Seminiferous tubules d. Tubuli recti Answer: c. The sperm cell originates in the seminiferous tubules and gradually works its way through the tubuli recti and rete testes to leave the testis itself. 163. How long is one cycle of spermatogenesis in the seminiferous tubules? a. 16 days b. 32 days c. 64 days d. 128 days Answer: c. A sperm cycle lasts about 64 days with new cycles starting all over the seminiferous tubules every 16 days. 164. What type of cell results from the meiotic process in the spermatozoa development? a. Spermatids b. Spermatogonia c. Primary spermatocytes d. Secondary spermatocytes 494

Answer: a. Spermatids are the result of meiosis of the secondary spermatocytes and, as a result, have just 23 total chromosomes or half of the number of chromosomes of the adult cell. 165. Which structure in the male reproductive tract is not paired? a. Seminal vesicle b. Ejaculatory duct c. Prostate d. Bulbourethral gland Answer: c. The prostate gland is not a paired structure; however, the others are paired in the male reproductive system. 166. What does sperm use for nourishment in order to achieve motility in the semen? a. Glucose b. Free fatty acids c. Amino acids d. Fructose Answer: d. Sperm cells preferentially use fructose as “fuel” to make ATP that powers the sperm cells. 167. Which part of the urethra is responsible for the secretion of the lubricant in the ejaculate at the time of male sexual arousal? a. Seminal vesicles b. Bulbourethral glands c. Prostate d. Corpus cavernosum Answer: b. The bulbourethral glands or Cowper’s glands make a salty lubricant in the ejaculate in order to lubricate the ejaculate in the urethra at the time of ejaculation.

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168. What part of the penis is removed during circumcision? a. Glans penis b. Corpus cavernosum c. Corpus spongiosum d. Prepuce Answer: d. The prepuce or foreskin will be removed surgically as part of the circumcision, usually done at the time of birth in young males. 169. What hormone directly causes the Leydig cells to produce testosterone in the male testes? a. Follicle stimulating hormone b. Gonadotropin releasing hormone c. Inhibin B d. Luteinizing hormone Answer: d. Luteinizing hormone directly causes the production of testosterone by the Leydig cells of the male testes? 170. Which hormone is produced in the male testes as part of the negative feedback loop in the male reproductive system? a. Estrogen b. Follicle stimulating hormone c. Inhibin B d. Luteinizing hormone Answer: c. Inhibin B is produced in the male testes so that there is inhibition of gonadotropin releasing hormone that causes a negative feedback loop to occur in the male reproductive system.

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171. What is lubricated by the Bartholin glands in the female genitalia? a. Fornix b. Cervix c. Vestibule d. Perineum Answer: c. The vestibule is where the Bartholin glands are located and is the area lubricated by the mucus secreted by these glands. 172. What microorganism predominates in the vaginal flora? a. Lactobacillus b. Bifidobacterium c. Escherichia coli d. Candida Answer: a. Lactobacillus species predominate in the vaginal flora. These bacteria secrete lactic acid, which reduces the vaginal pH to make the environment relatively inhospitable to other types of bacteria, particularly pathogenic bacteria. 173. What is the process of forming an egg called in the female reproductive system? a. Folliculogenesis b. Oogenesis c. Menstrual cycle d. Ovarian cycle Answer: b. The process of oogenesis is when the oogonia (primordial egg cell) forms an oocyte, which is the female gamete.

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174. During childhood and before puberty, what stage does oogenesis get arrested at? a. The oogonia stage b. First mitosis of the oogonia c. Meiosis I of the primary oocyte d. Meiosis II of the secondary oocyte Answer: c. The oogonia divides to make the primary oocyte, which stops in the beginning of meiosis I during much of childhood, only developing into a secondary oocyte after menarche. The arrest occurs during prophase of meiosis I. 175. What is the supporting cell in the female ovary called? a. Stromal cell b. Granulosa cell c. Oogonia cell d. Theca cell Answer: b. The supporting cell in the female ovary is called a granulosa cell. The cell starts out squamous in nature but, as it grows and proliferates, it become cuboidal in nature. 176. Which type of follicle in the female ovary is also referred to as an antral cell because it contains the antrum, filled with follicular fluid? a. Primordial follicle b. Primary follicle c. Secondary follicle d. Tertiary follicle Answer: d. The tertiary follicle is also referred to as the antral follicle because it consists of antral or “follicular” fluid.

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177. Which hormone is most responsible for the ovulation of the secondary oocyte? a. FSH b. LH c. GnRH d. Estradiol Answer: b. It is a surge of LH or luteinizing hormone that causes the release of the secondary oocyte in the process of ovulation. 178. What is the main hormone produced by the corpus luteum to support a pregnancy? a. Estradiol b. Estrone c. Testosterone d. Progesterone Answer: d. The corpus luteum makes a great deal of progesterone in order to support a potential pregnancy. It only lasts for about 12-14 days; then reduces to cause a period to occur. 179. Which is the major supporting ligament of the uterus in the pelvis? a. Broad ligament b. Uterine ligament c. Round ligament d. Uterosacral ligament Answer: a. The broad ligament is the main supporting ligament of the uterus, while the round ligament and uterosacral ligament are secondary uterine supportive ligaments.

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180. What is the innermost layer of the uterine tissue called? a. Perimetrium b. Stratum basalis c. Myometrium d. Stratum functionalis Answer: d. The stratum functionalis layer is the innermost lining of the uterus and sheds during menstruation if fertilization does not occur. 181. What is the chance that a person who is heterozygous for a dominant disorder like Huntington disease will pass it on to their children? a. 25 percent b. 50 percent c. 66 percent d. 100 percent Answer: b. The inheritance of a heterozygous dominant disorder involves a 50:50 chance or a 50 percent chance that they will pass it on to their children. 182. A woman is a carrier for an X-linked genetic disease. She has children with a normal male. What is the chance that their sons will be carriers for the disorder? a. Zero percent b. 25 percent c. 50 percent d. 75 percent Answer: a. The trait can be passed onto the male child or not passed onto the male child. There is no chance that the child will be a carrier because they do not have 2 X chromosomes.

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183. What is the outer layer around the egg cell as it travels through the fallopian tube called? a. Zona pellucida b. Capacitance layer c. Corona radiata d. Acrosome Answer: c. The corona radiata consists of granulosa cells that have come along with the egg in order to protect it and to release chemical attractants that attract the sperm to the egg. 184. What happens when calcium floods into the egg cell during fertilization? a. Cortical reaction b. Depolarization of the egg cell c. Capacitation d. Acrosomal reaction Answer: a. A cortical reaction takes place in which there are cortical granules that cause mucopolysaccharides and zonal inhibiting proteins to be released to the outside of the egg, causing hardening of the zona pellucida and a lack of ability to have more sperm enter the egg. 185. What is the zygote and its membranes called shortly after fertilization? a. Conceptus b. Blastomere c. Morula d. Blastocyst Answer: a. The zygote plus its membranes after fertilization are referred to as the “conceptus.”

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186. What are the cells called that first divide after fertilization? a. Conceptus b. Blastomere c. Morula d. Blastocyst Answer: b. The blastomere or “blastomeres” are what the first dividing cell(s) are called when the zygote divides several times. The resulting cells are smaller and do not appreciably change the overall size of the products of conception. 187. The initial embryo is disc shaped. What is the outer layer of this disc called? a. Epiblast b. Trophoblast c. Hypoblast d. Amnion Answer: a. The outer layer of the embryonic disc is called the epiblast. The inner layer is called the hypoblast and beneath this is the yolk sac. 188. There are three layers that form in the embryonic disc after the primitive streak forms. What does the ectoderm layer come from? a. Hypoblast b. Trophoblast c. Epiblast d. Allantois Answer: c. The cells of the epiblast go to become the ectoderm of the embryonic disc. These add to the mesoderm and the endoderm to form the three layers of the embryo.

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189. There are somites that form on either side of the notochord in the developing embryo. In organogenesis, these become all but what structure? a. Spinal cord b. Axial skeleton c. Dermis d. Skeletal muscles Answer: a. The somites become the axial skeleton, dermis, and skeletal muscle but it does not form the spinal cord itself. This is part of the neurulation process instead. 190. Which shunt in the fetal circulation bypasses the fetal circulation so that little blood gets to the fetal liver? a. Ductus arteriosus b. Ductus venosus c. Foramen ovale d. Umbilical vein Answer: b. The ductus venosus shunts blood away from the fetal liver after entering the fetus in the fetal vein, which contains oxygenated blood that is destined to the fetal circulatory system. 191. What genetic factor allows for the male and female genders in utero? a. There are female hormones created by the XX chromosome pair that degenerate the Wolffian ducts. b. There are genes in the X chromosome that make female hormones in order to cause female genitalia to grow. c. There is a gene in the Y chromosome that recruits male genes and suppresses female genes, leading to the male phenotype. d. The lack of female genes in the Y chromosome makes for a predominance of testosterone-producing genes, leading to the male phenotype.

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Answer: c. There is a specific SPY gene in the Y chromosome that recruits male genes and suppresses female genes, leading to the male phenotype. 192. What developmental change does not happen in the male at the time of puberty? a. Widening of the pelvis b. Elongation of the vocal cords c. Increased muscle mass d. Growth of facial hair Answer: a. In puberty, there is widening of the pelvis in the female; this doesn’t happen in males but the other things: elongation of the vocal cords, increased muscle mass, and facial hair growth happen in males at the time of puberty. 193. About how long is the average menstrual cycle in females? a. 7 days b. 14 days c. 28 days d. 40 days Answer: c. The average menstrual cycle is 28 days, with a range of 21-32 days. 194. Which hormone is generally lacking in the follicular phase of the menstrual cycle? a. Estrogen b. FSH c. Luteinizing hormone d. Progesterone Answer: d. Progesterone is made by the corpus luteum, which only happens after the follicular phase is over with. This hormone is relatively lacking in the follicular phase.

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195. Which hormone is responsible for ovulation in females? a. Luteinizing hormone b. Follicle stimulating hormone c. Progesterone d. Gonadotropin releasing hormone Answer: a. It is a surge in luteinizing hormone, called the “LH surge” that triggers the release of an egg in the act of ovulation. 196. After ovulation, how long does the oocyte survive before it must be fertilized? a. 8 hours b. 24 hours c. 72 hours d. 5 days Answer: b. The oocyte or egg cell will only survive about 24 hours before it degrades unless it is fertilized by the male sperm. 197. What is the human product of conception called when it forms a fluid-filled cavity with an inner cell mass and a trophoblast? a. Conceptus b. Morula c. Zygote d. Blastocyst Answer: d. The blastocyst is a structure formed by the growing embryo when it divides into an inner cell mass, a collection of fluid, and an outer trophoblast layer.

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198. What part of the zygote secretes human chorionic gonadotropin in order to cause a positive pregnancy test? a. Inner cell mass b. Ectoderm c. Trophoblast d. Hypoblast Answer: c. The trophoblast of the imbedded embryo will secrete hCG, which is what causes a positive pregnancy test. 199. Under normal circumstances, what is not a part of the human umbilical cord? a. Single umbilical artery b. Single umbilical vein c. Wharton’s jelly d. Paired umbilical arteries Answer: a. There are two umbilical arteries, a single umbilical vein, Wharton’s jelly, and remnants of the allantois in the umbilical cord. 200. What is it called when the three germ layers of the embryo become tube-shaped after being disc-shaped? a. Somite formation b. Neurulation c. Notochord formation d. Gastrulation Answer: d. Gastrulation is the process of taking all three germ layers of the embryo and turning it into a tubular structure after being a flat disc-shaped structure.

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College Level Anatomy and Physiology

Articles inside

Acid Base Physiology

The Lungs and Acid-Base Balance

The Ovarian Cycle and Oogenesis

Acid-Base Disorders

Kidney Physiology

Secretion and Reabsorption

Stomach Anatomy and Physiology

Urine Composition

Basic Human Metabolism

Large Intestine

The Pharynx

Nutrition and Metabolism

Mouth Anatomy and Physiology

Ventilation and Perfusion

Gas Exchange

Larynx

Lung Anatomy

Pulmonary Ventilation

T Cell Development and Maturation

Antibodies and B Cells

Regulation of the Cardiovascular System

Erythrocytes

Plasma Components

Conduction System of the Heart

Electrical Activity of the Heart

Cardiac Physiology

Hormone Types

Parathyroid Glands

Vision

Spinal Nerves

Cranial versus Somatic Nerves

Glial Cells of the PNS

Myelin

Ganglia

Types of Glial Cells

Skeletal Muscle Fibers

Muscles of the Trunk

The Pelvic Girdle

Joints

Fascicle Arrangements

The Scapula and Clavicle

The Lower Limb

Ribcage and Sternum

The Cranium

Skin Cancer

Bony Markings

Muscle Tissue

The Nails

The Dermis

Types of Tissues

The Hair