Pulmonary Medicine
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TABLE OF CONTENTS Preface........................................................................................................ 1 Chapter One: Pulmonary Anatomy and Physiology ..................................... 6 The Nose........................................................................................................................... 6 The Pharynx ................................................................................................................... 10 Larynx and Trachea ....................................................................................................... 10 Bronchi ........................................................................................................................... 12 The Respiratory Zone .................................................................................................... 13 Gross Anatomy of the Lungs.......................................................................................... 14 Mechanisms of Breathing .............................................................................................. 16 Respiratory Volumes...................................................................................................... 18 Control of Ventilation .................................................................................................... 20 Alveoli and Gas Exchange .............................................................................................. 21 Airway Defense Mechanisms ......................................................................................... 24 Pulmonary Circulation ................................................................................................... 25 Key Takeaways ............................................................................................................... 26 Quiz ................................................................................................................................ 27 Chapter Two: Pulmonary Testing .............................................................. 29 Spirometry ..................................................................................................................... 29 Lung Volume Measurement .......................................................................................... 32 Diffusing Capacity of the Lung for Carbon Monoxide or DLCO ................................... 35 Pulse Oximetry ............................................................................................................... 36 Methacholine Challenge Test ........................................................................................ 37
Six-Minute Walk Test .................................................................................................... 38 Arterial Blood Gases ...................................................................................................... 39 Exhaled Nitric Oxide Testing ......................................................................................... 39 Chest Radiology ............................................................................................................. 40 Ventilation Perfusion Scanning ..................................................................................... 43 Key Takeaways ............................................................................................................... 45 Quiz ................................................................................................................................ 46 Chapter Three: Approach to Respiratory Symptoms ................................. 49 Dyspnea .......................................................................................................................... 49 Working Up Dyspnea Patients....................................................................................... 52 Clinical Assessment of Dyspnea .................................................................................... 54 Evaluation of Cough ....................................................................................................... 58 Treating a Chronic Cough .............................................................................................. 61 Chest Pain ...................................................................................................................... 62 Key Takeaways ............................................................................................................... 65 Quiz ................................................................................................................................ 66 Chapter Four: Lung Infections .................................................................. 69 Community-Acquired Pneumonia................................................................................. 69 Treatment of Community Acquired Pneumonia ........................................................... 72 Ventilator-Associated Pneumonia ................................................................................. 73 Lung Abscesses .............................................................................................................. 75 Opportunistic Lung infections ....................................................................................... 77 Tuberculosis ................................................................................................................... 79 Key Takeaways ............................................................................................................... 84
Quiz ................................................................................................................................ 85 Chapter Five: Obstructive Lung Diseases .................................................. 88 Asthma or Reactive Airway Disease ..............................................................................88 Treatment of Asthma ..................................................................................................... 93 COPD .............................................................................................................................. 94 Treatment of COPD ....................................................................................................... 96 Alpha-1 Antitrypsin Disease .......................................................................................... 97 Key Takeaways ............................................................................................................... 99 Quiz .............................................................................................................................. 100 Chapter Six: Cystic Fibrosis .................................................................... 102 Introduction ................................................................................................................. 102 Treatment of Pulmonary Disease in CF ...................................................................... 106 Key Takeaways ..............................................................................................................110 Quiz ............................................................................................................................... 111 Chapter Seven: Bronchial Diseases .......................................................... 114 Bronchiectasis in Children............................................................................................ 114 Management of Bronchiectasis in Children ................................................................. 117 Bronchiectasis in Adults ............................................................................................... 119 Treatment of Adult Bronchiectasis ............................................................................... 121 Bronchiolitis ................................................................................................................. 123 Key Takeaways ............................................................................................................. 126 Quiz ...............................................................................................................................127 Chapter Eight: Lung Cancer .................................................................... 129 Non-small Cell Cancer ................................................................................................. 129
Small Cell Cancer ......................................................................................................... 133 Mesothelioma............................................................................................................... 136 Carcinoid Lung Cancer ................................................................................................ 138 Key Takeaways ............................................................................................................. 140 Quiz .............................................................................................................................. 142 Chapter Nine: Pulmonary Embolism ....................................................... 146 Introduction ................................................................................................................. 146 Diagnosis of Pulmonary Embolism ............................................................................. 148 Management of Pulmonary Embolism........................................................................ 150 Key Takeaways ............................................................................................................. 153 Quiz .............................................................................................................................. 154 Chapter Ten: Pulmonary Hypertension .................................................... 157 Types of Pulmonary Hypertension ...............................................................................157 Pulmonary Hypertension due to Diffuse Lung Disease .............................................. 159 Management of Pulmonary Hypertension ................................................................... 161 Prognosis of Pulmonary Hypertension ....................................................................... 163 Key Takeaways ............................................................................................................. 164 Quiz .............................................................................................................................. 165 Chapter Eleven: Pulmonary Edema ......................................................... 168 Cardiogenic Pulmonary Edema ................................................................................... 168 Noncardiogenic Pulmonary Edema............................................................................. 170 High Altitude Pulmonary Edema .................................................................................172 Key Takeaways ..............................................................................................................175 Quiz .............................................................................................................................. 176
Chapter Twelve: Infiltrative and Interstitial Lung Diseases ...................... 179 Idiopathic Interstitial Pneumonia ............................................................................... 179 Desquamative Interstitial pneumonia ......................................................................... 180 Respiratory Bronchiolitis-associated Interstitial Lung Disease ................................. 180 Acute Interstitial Pneumonia ....................................................................................... 181 Nonspecific Interstitial Pneumonia .............................................................................. 181 Hypersensitivity Pneumonitis ..................................................................................... 182 Sarcoidosis ................................................................................................................... 184 Eosinophilic Lung Disease ........................................................................................... 186 Pulmonary Alveolar Proteinosis .................................................................................. 189 Key Takeaways .............................................................................................................. 191 Quiz .............................................................................................................................. 192 Chapter Thirteen: Workplace Lung Diseases........................................... 195 Occupational-Induced Asthma .................................................................................... 195 Silicosis ......................................................................................................................... 197 Berylliosis ..................................................................................................................... 199 Asbestosis ..................................................................................................................... 201 Key Takeaways ............................................................................................................. 205 Quiz ..............................................................................................................................206 Chapter Fourteen: Pleural Diseases ........................................................ 209 Pleural Effusion ...........................................................................................................209 Pleural Infections .......................................................................................................... 211 Spontaneous Pneumothorax ....................................................................................... 213 Key Takeaways ..............................................................................................................217
Quiz .............................................................................................................................. 218 Chapter Fifteen: Mediastinal Diseases .................................................... 220 Mediastinal Tumors .....................................................................................................220 Pneumomediastinum................................................................................................... 222 Mediastinitis ................................................................................................................ 224 Key Takeaways ............................................................................................................. 226 Quiz .............................................................................................................................. 227 Chapter Sixteen: Disorders of Breathing ................................................. 231 Obstructive Sleep Apnea .............................................................................................. 231 Central Sleep Apnea ..................................................................................................... 233 Neuromuscular Diseases and Respiratory Disease ..................................................... 235 Key Takeaways ............................................................................................................. 237 Quiz .............................................................................................................................. 238 Chapter Seventeen: ARDS and Respiratory Failure ................................. 240 ARDS ............................................................................................................................240 Ventilatory Failure ....................................................................................................... 244 Mechanical Ventilation ................................................................................................ 245 ECMO ........................................................................................................................... 247 Key Takeaways ............................................................................................................. 249 Quiz .............................................................................................................................. 250 Summary ................................................................................................ 253 Course Questions and Answers ............................................................... 258 Answers to Quiz ...................................................................................... 299 Answers to Chapter One .............................................................................................. 299
Answers to Chapter Two .............................................................................................. 301 Answers to Chapter Three ........................................................................................... 302 Answers to Chapter Four ............................................................................................. 303 Answers to Chapter Five ..............................................................................................304 Answers to Chapter Six ................................................................................................ 305 Answers to Chapter Seven ...........................................................................................306 Answers to Chapter Eight ............................................................................................308 Answers to Chapter Nine .............................................................................................309 Answers to Chapter Ten ............................................................................................... 310 Answers to Chapter Eleven .......................................................................................... 312 Answers to Chapter Twelve ......................................................................................... 313 Answers to Chapter Thirteen ....................................................................................... 314 Answers to Chapter Fourteen ...................................................................................... 315 Answers to Chapter Fifteen ..........................................................................................317 Answers to Chapter Sixteen ......................................................................................... 318 Answers to Chapter Seventeen .................................................................................... 320 Answers to Course Quiz ............................................................................................... 322
PREFACE This course delves deeply into the subject of pulmonary medicine, which is something all medical practitioners will encounter on some level. There will be a discussion of the anatomy and physiology of the airways and an in depth understanding of the different disorders faced by the practitioner of pulmonary medicine. It includes the common disorders, such as asthma, pneumonia, and COPD, as well as complex lung diseases like the different pneumoconioses, pulmonary hypertension, and cystic fibrosis. The complicated issues of respiratory failure, ventilator management, and ECMO are also covered so as to understand the phenomena of the various lung diseases and how they are managed by the pulmonary specialist. Chapter one in the course introduces the topic of pulmonary medicine with a discussion of the anatomy and physiology of the respiratory system. This system includes the conducting zone and the respiratory zone, which will be discussed. The different mechanism of breathing and gas exchange are also covered. Lastly, the anatomy of the pulmonary circulation will be discussed as a review of normal pulmonary anatomy and physiology. Chapter two covers the basics of different types of pulmonary testing. There are multiple types of lung tests that can be done to evaluate a patient with lung symptoms. These include spirometry, pulse oximetry, and arterial blood gases, which are basic tests of lung function. The chest radiograph is an important radiographic tool that can detect multiple types of lung diseases. Finally, ventilation-perfusion lung scanning is covered as a tool for detecting pulmonary emboli in the lungs. The focus of chapter three in the course is the approach to the patient with different respiratory symptoms. The underlying pathophysiology of dyspnea is discussed as well as the approach in the diagnosis of the patient who has dyspnea as an outpatient. The approach and management of the individual who has subacute or chronic cough is covered as well as the diagnostic approach to the patient who has chest pain for pulmonary and non-pulmonary diseases.
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The topic of chapter four is lung infections. The most common lung infection seen is community-acquired pneumonia. These are infections that happen to individuals in the community setting. Ventilator-associated pneumonia is also covered because there are many more organisms that can cause these infections that just aren’t seen in community-acquired pneumonia. Lung abscesses are uncommon infections of the lung from a variety of pathogens; these are more difficult to treat than pneumonia. Opportunistic lung infections are seen in immunosuppressed patients and represent a wide variety of bacterial and non-bacterial pathogens. Tuberculosis manifestations and treatment are also a part of this chapter. Chapter five in the course is a discussion of the different obstructive lung diseases. The two most common obstructive lung diseases are asthma or reactive airway disease and COPD or chronic obstructive pulmonary disease. Asthma can be seen at any age but normally begins in childhood. COPD is almost always a disease of older adults and is usually seen in individuals with a long cigarette smoking history. The chapter also covers alpha-1 antitrypsin disease, which is a genetic disease that leads to obstructive lung disease. The focus of chapter six is the autosomal recessive disease known as cystic fibrosis. This affects various aspects of the body, including the lungs, digestive tract, reproductive system, and sweat glands. A main feature of the disease is related to the lungs, with difficulty clearing pathogens and the frequent occurrence of severe lung infections. While CF traditionally involved a markedly shortened lifespan, current treatment has lengthened this so that individuals can live longer and healthier lives. Chapter seven in the course involves a discussion of two different bronchial diseases. Bronchiectasis is disease of distortion and dilation of the bronchial tree that can affect either children or adults. The manifestations and treatment of the disease as it exists in children and as it is seen in adults are covered separately. Bronchiolitis is an infectious disease of the bronchioles that mainly affects infants and children. The characteristics of the disease and the treatment are discussed as part of this chapter. Chapter eight in the course introduces lung cancer and its manifestations. There are two main types of primary lung cancer that are most commonly seen: non-small cell
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lung cancer, which is the most common, and small cell lung cancer. Most of these cancers are tobacco-related. Less commonly, patients can have a malignancy of the pleura, seen in individuals who’ve been exposed to asbestos, usually in the workplace. A rarer type of lung cancer is carcinoid cancer of the lungs, which is also covered as part of this chapter. The main focus of chapter nine is the acute pulmonary embolism. The most common cause of this is a deep venous thrombosis of the lower extremity that travels from the leg to the lungs, leading to a significant ventilation-perfusion mismatch. Some patients will have milder disease and will present with symptoms that are survivable. Others will have a massive embolus and will have a cardiac arrest from which they do not recover. The presentation, diagnosis, and management of pulmonary emboli are covered in this chapter. Chapter ten in the course is about pulmonary hypertension. It involves any condition that leads to a mean pulmonary artery pressure of greater than or equal to 20 millimeters of mercury. There are several different groups that are represented by having pulmonary hypertension as part of the features. The different groups of pulmonary hypertension are based on the underlying cause of the disease process. Special emphasis is given of group 3, which is pulmonary hypertension due to chronic lung disease and/or hypoxemia. The treatment of pulmonary hypertension is discussed as well. Chapter eleven talks about the different causes and manifestations of pulmonary edema. Pulmonary edema can be cardiogenic in nature or related to various types of lung disease. One cause of pulmonary edema is high altitude, which can cause this problem in the absence of any type of heart problem or pulmonary condition. The various treatments for pulmonary edema are covered as a part of this course; the treatment depends on the underlying etiology. There are many different infiltrative and interstitial lung diseases discussed in chapter twelve in the course. This includes idiopathic interstitial pneumonia, which is actually a wide range of diseases involving abnormalities of the interstitium of the lungs. Other related disorders include sarcoidosis, which is infiltrative, and hypersensitivity
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pneumonitis. The relatively uncommon diseases of the lungs called eosinophilic lung disease and pulmonary alveolar proteinosis are also covered in the chapter. The focus of chapter thirteen is workplace lung injuries. A common workplace lung injury that can be seen in a variety of workplace situations is occupational-induced asthma. This is not much different from normal asthma but tends to be triggered by workplace situations. There are specific lung diseases that are also related to workplace exposure. These include silicosis, asbestosis, and berylliosis, which are collectively called pneumoconioses. These are specific lung disease brought on by the inhalation of a foreign substance—usually on a chronic basis in the workplace. Chapter fourteen in the course talks about several different types of pleural diseases. Pleural effusions can be transudative or exudative, depending on the cause of the effusion. They can also be unilateral or bilateral. Pleural infections may be primary or may be secondary to extension of other lung infections. This chapter also covers the causes and manifestations of pneumothoraces, which can be secondary to trauma or to spontaneous disease of these membranes. The main topics of chapter fifteen include those involving the mediastinal space. This is typically a small centrally-located space that is rarely involved in disease processes. The chapter discusses benign and malignant tumors of the mediastinum as well as pneumomediastinum, which involves air in the mediastinum. Fibrosing mediastinitis is a complication of certain fungal infections of the lungs that can present in the patient with underlying lung disease. Chapter sixteen in the course involves a discussion of the different disorders that affect breathing itself. Perhaps the most common of these is obstructive sleep apnea, seen in patients of all ages and presentations. Less commonly seen is central sleep apnea, in which the problem is caused by a defect in the respiratory centers of the brain. Lastly, respiratory patterns can be greatly affected by neuromuscular diseases. There is a variety of neuromuscular diseases that can adversely affect the ability to breathe spontaneously. The focus of chapter seventeen in the course is severe lung diseases that can lead to ventilatory failure. Acute respiratory distress syndrome is a severe response to different
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lung insults that often leads to ventilatory failure. The management of ventilatory failure and hypercapnia is also covered in this course as is the basics of mechanical ventilation. ECMO is used primarily for cardiorespiratory surgery, which is discussed as part of this chapter.
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CHAPTER ONE: PULMONARY ANATOMY AND PHYSIOLOGY This chapter introduces the topic of pulmonary medicine with a discussion of the anatomy and physiology of the respiratory system. This system includes the conducting zone and the respiratory zone, which will be discussed. The different mechanism of breathing and gas exchange are also covered. Lastly, the anatomy of the pulmonary circulation will be discussed as a review of normal pulmonary anatomy and physiology. Anatomy of the Airways The respiratory system is divided functionally into two zones: the conducting zone and the respiratory zone. The conducting zone involves those regions that do not participate in gas exchange, while the purpose of the conducting zone is to participate in gas exchange. In the conducting zone, the structures provide a passageway for incoming and outgoing air. It gets rid of debris and removes pathogens, warming and humidifying inhaled air. There are specialized structures that sense odors in the nasal passages and that metabolize airborne carcinogens (in the epithelium of the bronchial tree).
THE NOSE The external nose has the skeletal structures that give the typical appearance of the nose itself. There is a root that is located between the eyebrows. The bridge of the nose will be the part of the nose that connects the root to the remainder of the nose. The dorsum nasi is what the length of the nose is called. The tip of the nose is called the apex. The nostrils are made up of the alae of which the singular is ala. The alae are made of cartilage and form the naris (of which the plural is nares) or nostrils. The philtrum is the dip in the skin that connects the nose to the upper lip. Figure 1 shows an image of the nose:
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Figure 1.
Beneath the skin of the nose is the skeleton, made of bone. The root and bridge are made of bone, while the part that sticks out is made of cartilage. This is why a skeleton looks like it is missing a nose. The nasal bone is actually one of a couple of bones that lie under the bridge and root of the nose. It connects the nose to the frontal and maxillary bones of the face. There is septal cartilage that attaches to the nasal bone to make the dorsum nasi. The alar cartilage makes the nares and apex of the nose. The nostrils open up into the nasal cavity, which has two sections divided by the nasal septum, which is made by septal cartilage, the perpendicular plate of the ethmoid bone, and the vomer bone. There are three projections on the lateral aspect of the nasal cavity: the inferior, middle, and superior nasal conchae. Just the inferior concha is a separate bone, while the other two conchae are part of the ethmoid bone. The conchae of the lateral nasal cavity serve the major function of increasing the surface area of the nasal cavity, leading to increased trapping of debris and an increased
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humidification of the air. There are meatuses beneath these bones that open into the facial paranasal sinuses. The floor of the nose and the upper part of the mouth is the palate. There is a hard palate anteriorly, which consists of bone. The soft palate is muscular. Figure 2 shows the anatomy of the nasal cavity:
Figure 2.
There are four sinuses that comprise the paranasal sinuses—each named by the bone in which they reside: the frontal sinus, the maxillary sinus, the ethmoid sinus, and the sphenoidal sinus. It is the sinuses that produce mucus; they also make it so that the head/skull isn’t so heavy. The anterior part of the nasal cavity is lined with mucous membranes, hair follicles, and sebaceous glands that aid in getting rid of debris in the nose as it is inspired. There is also specialized olfactory epithelium that detects odors.
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The majority of the nose and the entirety of the sinuses is lined with pseudostratified ciliated columnar epithelium, which is called respiratory epithelium. It contains goblet cells that make mucus, which helps to trap pathogens and debris. The cilia beat to remove this mucus and debris toward the throat, which is then swallowed. Cold air will slow this process, which is why the nose runs in cold environments. Capillaries beneath the epithelium warm the air through the process of convection. Another defensive activity of the upper respiratory passage is the production of defensins. Defensins are made by the serous and mucus-producing cells of the respiratory passages, which also secrete lysozyme. Both lysozyme and defensins have antibacterial properties. There are also immune cells in the deep connective tissue of the respiratory passages that help to protect the tissues from pathogens. Figure 3 shows the respiratory epithelium:
Figure 3.
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THE PHARYNX The pharynx is a tube that is made primarily by skeletal muscle and a type of mucous membrane epithelium. There are three parts: the nasopharynx, the oropharynx, and the laryngopharynx. The nasopharynx is behind the nose itself and is used just for breathing. There is a pharyngeal tonsil or adenoid lying at the top of the nasopharynx. This tonsil is a lymphoid organ that helps to get rid of pathogens during inhalation. The uvula is a teardrop-shaped structure at the back of the soft palate. It moves during swallowing and helps close off the nasopharynx so food does not enter the nose during swallowing. There are also Eustachian tubes in the nasopharynx that connect the middle ear cavity to the nasopharynx. The oropharynx is both a passageway for food and air. It is located behind the oral cavity and has the fauces as the dividing structure between the two. The epithelium is stratified squamous epithelium. There are two sets of tonsils there; the palatine tonsils (on either side of the fauces) and the lingual tonsil (at the base of the tongue). These also contain lymphoid tissue that destroys pathogens. The laryngopharynx is beneath the oropharynx. It is used for food and air and is where the GI tract and respiratory tract diverge. Anteriorly, it opens into the larynx, while posteriorly, it opens into the esophagus.
LARYNX AND TRACHEA The larynx is made from cartilage and connects the pharynx to the trachea. It is formed through the connection of multiple pieces of cartilage. There are three large pieces: the anterior thyroid cartilage, the superior epiglottis, and the inferior cricoid cartilage. The thyroid cartilage is the biggest piece and contains the Adam’s apple. The cricoid cartilage is ring-shaped. There are three smaller cartilages that are paired: the arytenoids, the cuneiforms, and the corniculates. Figure 4 shows the anatomy of the larynx:
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Figure 4.
The epiglottis is attached to the thyroid cartilage. It is flexible and covers the trachea when swallowing and rests on the glottis. The glottis is made by the true vocal cords, the vestibular folds, and the space between the folds. The vestibular folds are folded mucous membranous structures that make up the false vocal cords. The true vocal cords are attached to the thyroid and arytenoid cartilages by a muscle. These true cords will oscillate, making sound. The trachea or windpipe has the larynx at the superior end. It consists of between 16 and 20 stacked pieces of hyaline cartilage—each of which is C shaped, opening in the back. The cartilages are held together by dense connective tissue. The trachealis muscle and connective tissue together form what’s called the fibroelastic membrane, which closes the posterior surface of the trachea. It is lined with the typical respiratory epithelium seen in the rest of the respiratory tract. Figure 5 shows the anatomy of the trachea:
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Figure 5.
BRONCHI The trachea ultimately branches into the left and right primary bronchi. They are lined by respiratory epithelium containing goblet cells. There is nervous tissue at the carina that causes severe coughing if food or a foreign body is present. There are rings of cartilage that support the bronchial structure so they do not collapse. These are part of the conducting zone because they do not participate in gas exchange and contain debristrapping mucus.
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Bronchioles are defined as being 1 millimeter in diameter or less; they come off the tertiary bronchi and end in terminal bronchioles. There are more than a thousand terminal bronchioles per lung. They have muscular walls that can increase or decrease their size, affecting airflow.
THE RESPIRATORY ZONE These structures are directly involved in the exchange of respiratory gases. This zone starts at the respiratory bronchiole, which is the smallest bronchiole. The bronchiole leads to an alveolar duct, which opens into a cluster of various numbers of alveoli. Figure 6 shows what the alveoli and their circulation look like:
Figure 6.
The alveolar duct is a tube made from connective tissue and alveoli. One alveolus is a small, grape-like structure that is involved in gas exchange. Many alveoli together form an alveolar sac. One alveolus is about 200 micrometers in diameter and stretch because
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of elastic walls. The stretched walls allow for excellent gas exchange. The alveoli are connected to each other by alveolar pores, which help maintain the pressure equalized throughout the lungs. There are three types of cells that make up the alveoli. Type I alveolar cells are squamous epithelial cells, making up 97 percent of the surface area of the cells. They are highly gas-permeable. Type II alveolar cells secrete pulmonary surfactant, which is made from protein and phospholipids. The mobile cells are the alveolar macrophages, which are phagocytic and remove pathogens and debris. The type I alveolar cell has a thin elastic membrane associated with it. It borders the endothelial lining of the capillaries—all together making the respiratory membrane (the alveolar cell, the basement membrane, and the endothelial cell). Together, these are thin enough at half a micrometer so that simple diffusion of oxygen and carbon dioxide can happen.
GROSS ANATOMY OF THE LUNGS The lungs are pyramidal in shape and are paired organs, connected only by the trachea and bronchi. The diaphragm is located inferior to the lungs and is the main structure that is involved in the work of breathing. The right lung is shorter than the left and has three lobes, while the left lung has two lobes and a lingula that overlies part of the heart. There is a cardiac notch on the left side to fit the heart up next to the lungs. The apex of the lungs is on the top, while the base of the lung is on the bottom. The costal surface is the part near the ribcage and the mediastinal surface faces the midline of the body. The mediastinal surface contains the hilum, which contains the main vessels entering and leaving the heart. Figure 7 depicts the main anatomy of the lungs:
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Figure 7.
The three lobes of the lungs are the superior, middle, and inferior lobes. The two lobes of the lungs are the superior and inferior lobes. The lungs are also divided into bronchopulmonary segments, which consist of a tertiary bronchus, its artery, and the parenchyma that they supply. In some cases, there can be disease of a bronchopulmonary segment that necessitates its removal, which can be accomplished without damaging other segments. A lobule is a section of lung that is supplied by a bronchiole; an interlobar segment divides each lobule. The lung has a blood supply called the pulmonary circuit or pulmonary circulation. We will talk more about that in a minute. The blood supply starts as deoxygenated blood that becomes oxygenated as part of the gas exchange process. All vessels end and leave the heart via the hilum. The parasympathetic and sympathetic nervous system are involved in the innervation of the heart. The parasympathetic nervous system leads to bronchoconstriction, while the sympathetic nervous system leads to bronchodilation. The cough reflex and the
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regulation of oxygen and carbon dioxide levels are determined by the autonomic nervous system as well. Sensation of the lungs comes from the vagus nerve. The pulmonary plexus is formed by nerves located at the hilum. The nerves follow the bronchi, branching to serve the blood vessels, glands, and muscle fibers that are a part of the lungs. The lining of the lungs involves a serous membrane called the pleura. There are two layers of the pleura. There is a visceral pleura that is directly attached to the lung surface and that goes into the fissures of the different lobes. The parietal pleura is adherent to the chest wall, the diaphragm, and the mediastinum. Between the two layers is the pleural cavity. A few millimeters (10 to 20 milliliters) of pleural fluid is made by the mesothelial layers from both pleural layers, which lubricates the surfaces. The fluid also creates surface tension to maintain the lung position during breathing and is adhesive enough to allow the lungs to enlarge during inspiration. Finally, it acts to prevent movement of pathogens between the different parts of the lungs.
MECHANISMS OF BREATHING Breathing involves changing the intra-alveolar pressure in order to have air enter and leave the lungs. The ability to breathe depends on the pressure of air in the atmosphere and the pressure of air in the lungs. Both inspiration and expiration depend on the differences in pressure between the lungs and the atmosphere. There are several gas laws that apply to breathing. The first is Boyle’s law, which states that, at a constant temperature, the change in volume of a container will change its pressure. As the volume is decreased the pressure is increased. There are three pressures that play a role. The first is the atmospheric pressure, which is the air pressure in the surrounding air. It is equal to 1 atmosphere or 760 millimeters of mercury. For respiration, however, the atmospheric pressure is set at zero, with positive pressures being greater than atmospheric pressure and negative pressures being less than atmospheric pressure.
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The intra-alveolar pressure is the pressure of air in the alveoli. It is also called the intrapulmonary pressure. It is always equalized with the atmospheric pressure. The transpulmonary pressure is the pressure between the lungs and the pleural space. It is about 4 millimeters of mercury different from the atmospheric pressure. The intrapleural pressure is the pressure between the parietal and visceral pleura. It is negative 4 millimeters compared to the intra-alveolar pressure. There are forces within the thorax that lead to the negative intrapleural pressure. One of these is the elasticity of the lungs themselves. This pulls the lungs away from the thoracic wall. The surface tension of the fluid in the alveolus creates an inward pull on the lung tissue. The opposing force in the lungs is the surface tension in the pleural cavity, which pulls the lungs outward. This depends on the having the right amount of fluid in the intrapleural space. Finally, the elasticity of the chest wall opposes the inward pull. The outward pull is greater than the inward pull so as to keep the lungs expanded. Breathing depends on the contraction and relaxation of the different muscle fibers of the thorax and diaphragm, with the lungs being passive in the breathing process. The negative intrapleural pressure keeps the lungs adherent to the chest wall when breathing happens. It’s the muscle movements that allow the air to enter or leave the lungs. One of the main things that affect airflow is the resistance generated by the diameter of the airways. The thoracic wall compliance is also a factor. This compliance is the ability of the thoracic wall to stretch under pressure. The thoracic cavity needs to expand in order for inspiration to occur and the chest wall compliance plays a big role. Things like obesity can affect thoracic wall compliance, which affects the amount of air that can get into or outside the lungs. The basic driving force behind pulmonary ventilation is the flow of air down a pressure gradient. Air will flow into the lungs due to pressure differences between the atmospheric pressure and the intra-alveolar pressure. The air flows out for the same reason—an increased intra-alveolar pressure versus the atmospheric pressure. There are two main events that happen in pulmonary ventilation. The first is inspiration and the second is expiration. One respiratory cycle is inspiration plus expiration. There
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are two muscle groups involved in the normal inspiration: the external intercostal muscles and the diaphragm. There are other muscles that can be involved if a larger breath is indicated. The diaphragm moves downward and the ribs move upward and outward. This expands the ribcage and, because the lungs are adherent to the rib cage, the lungs expand as well. This causes a decrease in intra-alveolar pressure and air rushes into the lungs. Expiration is normally passive so that no energy is necessary to push air out of the lungs. The lungs are elastic so they recoil as the diaphragm and intercostal muscles relax. There is a subsequent increase in the intrapulmonary pressure so that air leaves the lungs. There are different types of breathing. Quiet breathing is called eupnea. It occurs at rest and does not require cognitive thought. It does require contraction of the diaphragm and external intercostal muscles. Deep breathing or “diaphragmatic breathing” involves contraction of the diaphragm. Shallow breathing or “costal breathing” depends on the contraction of the intercostal muscles. Forced breathing or “hyperpnea” happens with things like singing or exercising. Muscle contraction is required for both inspiration and expiration. It requires the addition of the scalene muscles for inspiration and the oblique muscles of the abdomen and the internal intercostals of the ribcage in order for this type of respiration to occur.
RESPIRATORY VOLUMES There are several respiratory volumes important in the respiratory cycle. The tidal volume is about 500 milliliters and is the volume inhaled or exhaled during quiet breathing. The expiratory reserve volume is about 1200 milliliters and is the amount of air that can be forcefully exhaled. The inspiratory reserve volume is the amount that can be inhaled deeply. The residual volume is the amount that must stay in the lungs after forced exhalation to keep the alveoli from collapsing. Figure 8 describes a normal breath:
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Figure 8.
In addition to these volumes, there is the anatomical dead space. This is the air that is present in the airways that cannot get exchanged because it is kept within the bronchi. The alveolar dead space is that which is in the alveoli that are not functioning because of a ventilation/perfusion mismatch or because there is disease in the alveoli. This can happen because of a pulmonary embolism, for example. The total dead space is the anatomical dead space and the alveolar dead space together.
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CONTROL OF VENTILATION While breathing can be controlled, it normally happens without thinking. The respiratory rate is the number of breaths per minute. Its rate can increase or decrease, depending on the condition. The medulla oblongata in the brain contains the respiratory center, which breathes at a rate that depends on the O2 level, the CO2 level, and the pH of the blood. The respiratory rate will vary with age, being between 30 and 60 breaths per minute prior to one year of age and about 12 to 18 breaths per minute in adulthood. There are several factors that play into respiration. The medullary respiratory center sets the main breathing rhythm. The ventral respiratory group or VRG integrates the incoming data in order to set the breathing rhythm, while the dorsal respiratory group or DRG can integrate input from the different stretch receptors and chemoreceptors peripheral to the brain. The pontine respiratory group or PRG modifies and influences the function of the medulla oblongata. The pontine respiratory group is comprised of the pneumotaxic center and the apneustic center. The hypothalamus monitors the body temperature and emotional state to regulate breathing. The aortic body and carotid body will monitor the pCO2 and pO2 of the blood as well as the pH. The cortical areas of the brain can control voluntary breathing. There are also proprioceptors in the joints and muscles that send impulses to the brain for increasing the respiratory rate with exercise. There are two reflexes: an irritant reflex that protects the lower airways from foreign bodies and an inflation reflex that protects the lungs from over-inflation. The dorsal respiratory group or DRG maintains a constant breathing rhythm, while the ventral respiratory group or VRG is involved in forced breathing. The VRG stimulates the accessory muscles that are involved in the act of forced breathing. This results in forced expiration. The pontine respiratory center or pontine respiratory group consists of a pair of nerve clusters in the apneustic center that stimulate the DRG in order to control the depth of breathing in deep breathing. The pneumotaxic center is a cluster of neurons that inhibit
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the DRG, allowing the individual to relax after inspiration, allowing for control over the rate of respirations. These regions of the brain do not act in a vacuum. They respond to basic systemic stimuli. The greater the stimulus, the greater is the response. The CO2 concentration is the major factor that controls the respiratory drive in the healthy person. There are central chemoreceptors in the brain and brainstem and peripheral chemoreceptors in the aortic arch and carotid arteries. An increased CO2 level will stimulate the respiratory effort, while a decreased CO2 level will inhibit the respiratory effort. Lactic acid will lower the pH and will increase the respiratory rate; lactic acid will increase during intense exercise. The hypothalamus and the cortex are also involved in influencing breathing. The hypothalamus responds to changes in temperature, emotions, and pain signals. These include things like the fight-or-flight response, which will act to increase the respiratory rate in response to stress.
ALVEOLI AND GAS EXCHANGE Gas exchange is the ultimate goal of the respiratory system. Pulmonary ventilation is what it’s called when the body brings air to the alveoli for the process of gas exchange. External respiration is what it is called when the gas exchange occurs at the level of the alveoli. In order to understand this type of respiration, you need to also understand Dalton’s gas law or the law of partial pressures. It indicates that the sum total of a mixed gas pressure is equal to the sum of the partial pressures of each gas in the mixture. Most of air is nitrogen gas at more than 78 percent. Oxygen is next at 21 percent. CO2 makes up just 0.04 percent of the total gas in atmospheric air. Water vapor actually has a higher concentration than CO2 at 0.4 percent of atmospheric air. This partial pressure is important because a gas will move toward from its area of higher partial pressure to its area of lower partial pressure. There is also Henry’s law to consider and that states that the concentration of gas in a liquid medium is proportional to both its partial pressure and its solubility in the liquid. 21
Nitrogen has a very high partial pressure in atmospheric air but it has a low solubility in blood so it does not have a high blood concentration in this liquid. The major exception is scuba divers that breath in a mixture of gases that have a higher partial pressure of nitrogen underwater. This leads to a potentially fatal level of nitrogen dissolved in blood. In alveolar air, the water vapor pressure is higher because air is humidified as it enters the lungs. The nitrogen percentage is 75 percent; the oxygen percentage is about 14 percent; the water vapor percentage is 6.2 percent; and the CO2 percentage is 5.2 percent. The partial pressure of oxygen is 104 millimeters of mercury and the partial pressure of CO2 in the alveolar air is 47 millimeters of mercury. Gas exchange occurs at the lungs and at the tissues. External respiration is the exchange of gases at the alveoli, while internal respiration is that exchange that occurs in the tissues. Gases exchange via simple diffusion with no energy required. They follow the pathway set up by the partial pressures of the gases and by the concentration of the gas in the liquid plasma. The respiratory membrane is highly permeable to both oxygen and carbon dioxide and the alveoli offer up a large surface area. Most oxygen is picked up by hemoglobin in the pulmonary capillaries. Some carbon dioxide is taken up by hemoglobin in the tissues but most is dissolved in plasma. Some carbon dioxide gets transferred via bicarbonate, which goes to carbon dioxide and water through the action of carbonic anhydrase in the red blood cell. The solubility of oxygen isn’t high in blood but there is a big difference in the partial pressure of oxygen in the alveoli (at 104 millimeters of mercury) versus the capillaries (at 40 millimeters of mercury). This is what allows oxygen to diffuse into the bloodstream. The difference between the partial pressure of carbon dioxide at the alveoli is not as great at 5 millimeters of mercury. This is offset by the greater solubility of carbon dioxide in the blood versus oxygen so that carbon dioxide can leave the plasma and enter the alveolar side in the lungs. Only about 1.5 percent of all blood oxygen is dissolved in the plasma. Most enter the RBC and get picked up by hemoglobin, which can bind up to four oxygen molecules per heme molecule. The end result is oxyhemoglobin, which is formed whenever oxygen binds to hemoglobin, contributing to its bright red color. The binding of one oxygen
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molecule facilitates the binding of the other four molecules. In the same way, the dropping off of one oxygen molecule facilitates the dropping off of the other three. A hundred percent saturation comes from all four heme molecules attached to oxygen. Most blood is 95 to 99 percent saturated. This relationship between oxygen and hemoglobin binding leads to an oxygen dissociation curve. At lower partial pressures of oxygen, there is less of a percent saturation of hemoglobin. There are two different factors that determine the dissociation of oxygen from hemoglobin. Highly active tissues, such as muscle, have a lower partial pressure of oxygen. The partial pressure of oxygen in fatty tissue is higher because less oxygen is used. Less oxygen dissociates in fatty tissue than in muscle tissue. Higher temperatures will cause oxygen and hemoglobin to dissociate to a greater degree, while low temperatures inhibit this dissociation process. This is what’s seen in highly metabolic tissues. Hormones like growth hormone, thyroid hormone, epinephrine, and androgens will stimulate the 2,3-bisphosphoglycerate production in the RBCs. This molecule is a metabolic product of glycolysis and promotes the dissociation of oxygen from hemoglobin. The Bohr effect indicates that there is a relationship between blood pH and oxygen’s affinity for the hemoglobin molecule. Acidotic pH levels will promote oxygen dissociation, which is what’s seen in highly metabolic tissues. Blood pH will decrease with CO2, carbonic acid, and lactic acid in the tissues. These will promote oxygen dissociation. Carbon dioxide, as mentioned, is transported as bicarbonate, on hemoglobin, and in solution in plasma. About 7 to 10 percent is transported as solubilized CO2. Most (about 70 percent) is transported as bicarbonate and then turned into carbon dioxide and water via carbonic anhydrase in the RBCs. The bicarbonate leaves the RBCs by switching places with chloride in the plasma. The CO2 is rapidly diffused across the respiratory membrane into the alveoli, where it is exhaled. About 20 percent of CO2 gets bound by hemoglobin to make carbaminohemoglobin. It dissociates from the
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hemoglobin in the alveoli and gets passed through to the outside of the body during exhalation. The Haldane effect determines the affinity of hemoglobin for oxygen and carbon dioxide. Hemoglobin that is completely saturated with oxygen will not easily bind to carbon dioxide. When oxygen is not bound to the hemoglobin molecule, hemoglobin will rapidly bind to carbon dioxide.
AIRWAY DEFENSE MECHANISMS There are aspects of the airways that defend against pathogens and debris. The bifurcation of the airway and the anatomy of the nasopharynx will not allow foreign particles greater than 2 to 3 micrometers in diameter to pass through to the lower airways. Coughing generates turbulence that also defends the lower airways. Cilia in the respiratory tract beat upward to get rid of debris in the airways. Mucus gel in the airways will prevent pathogenic bacteria from entering the lungs. Secretory IgA made by the immune system will bind and neutralize viruses and toxins and will prevent the passage of bacteria across the airway epithelium. A nonspecific barrier to pathogens is the presence of lactoferrin, lysozyme, and peroxide in the airways. Lactoferrin is bactericidal and peroxides act as oxygen free radicals to kill or stop bacteria. Lysozyme will kill bacteria and is made from macrophages or neutrophils in the lungs. Epithelial cells act as a mucosal barrier. They are adherent to one another through several junctions, preventing the passage of pathogens. Pathogens that get through can be killed by phagocytic dendritic cells just beneath the epithelial basement membrane. They can take up antigens and migrate to the lymph nodes of the lungs, where they activate T cells, which are specific to a particular antigen. Eosinophils, basophils, and mast cells contribute to the activation of the respiratory tract in allergic diseases. Within the alveoli, the type I cells and type II cells play a minor role in the immune system milieu of the alveoli. Surfactant will contribute to the human host lung defenses and enhance the killing of microbes. Alveolar macrophages are phagocytic cells that provide the major first line of defense against things that enter the alveoli. It is the job 24
of these cells to neutralize pathogens or particles as well as to recruit both neutrophils and other types of mononuclear cells. The alveoli contain about ten percent lymphocytes, including helper T cells, cytotoxic T cells, and NK cells. About 5 percent are B lymphocytes. They get activated by the dendritic cells in the lungs. Neutrophils get activated in bacterial infections and become the most active cells when the alveolar macrophages fail.
PULMONARY CIRCULATION While ventilation is the movement of air into and outside of the lungs, perfusion is the flow of blood through the pulmonary vasculature. The ventilation and perfusion should be roughly equal and balanced in order to have adequate exchange of oxygen and carbon dioxide. When ventilation is not sufficient for a particular alveolus, blood is redirected to alveoli that are receiving enough ventilation. This happens by constricting flow in the arterioles away from the malfunctioning alveolus. Vasodilation happens in normal alveoli in order to have adequate perfusion to these alveoli. The pulmonary circuit is the system of blood vessels that supply the lungs. This circuit starts at the right atrium and passes through the right ventricle. It is a single vessel that leaves the right ventricle as the pulmonary trunk. The pulmonary semilunar valve will prevent backflow of blood during diastole into the right ventricle. Shortly after the blood leaves the pulmonary trunk it bifurcates into the left and right pulmonary artery. These branch several times to end in multiple pulmonary capillaries. After exchanging oxygen and carbon dioxide, the blood vessels enlarge to end within the pulmonary veins. There are four pulmonary veins, two on the right and two on the left.
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KEY TAKEAWAYS •
The upper airway involves the nose, pharynx, and larynx.
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There is a conducting zone and a respiratory zone in the airways. The conducting zone conducts air and the respiratory zone exchanges gases.
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There are three major alveolar cells: type I cells, type II cells, and alveolar macrophages.
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A bronchopulmonary segment has its own terminal bronchiole and its own arterial supply.
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The respiratory centers are contained with the medulla and the pons.
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There are several gas laws that determine the way gases behave in the body.
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Oxygen is mainly carried on hemoglobin, while carbon dioxide is carried as bicarbonate, dissolved CO2, and as carbaminohemoglobin.
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There are multiple lines of defense against pathogens and debris that get into the airways or alveoli.
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The pulmonary circuit starts at the pulmonary trunk and ends at four pulmonary veins.
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