General pathology review

PATHOLOGY 2013 BATCH

the study and diagnosis of disease", the study of the structural, biochemical and functional changes in cells, tissues, and organs that underlie disease

BHAGATH M S

RAJEEV BISWAS

CONTENT A. GENERAL PATHOLOGY

1

Adaptation and Injury of Cell and Tissue

6 LECTURES

2

Tissue Repair

3 LECTURES

3

Hemodynamic Disorder and Abnormalities of Blood Supply Inflammation

5 LECTURES

Neoplasia and the Malignancies of Hematopietic and Lymphoid Systems

12 LECTURES

4 5&9

6 LECTURES

B. SYSTEMIC PATHOLOGY 6

Disease of Cardiovascular System

8 LECTURES

7

Disease of Respiratory System

6 LECTURES

8

Disease of Digestive System

9 LECTURES

9

Disease of Immunity

3 LECTURES

10

Disease of the Urinary System

5 LECTURES

11

Disease of the Genital System and Breast

3 LECTURES

12

Disease of the Endocrine System

3 LECTURES

13

Disease of Nervous System

3 LECTURES

14

Infectious Diseases

8 LECTURES

PAGE 1

1. Adaptation and Injury of Cell and Tissue

6 LECTURES

TO MASTER 1. The concepts and lesion of adaptation: atrophy, hypertrophy, hyperplasia, metaplasia 2. The morphological changes of intracellular and extracellular accumulation in gross and light microscopic levels: hydropic degeneration, fatty change, hyaline change (connective tissue, vascular wall, intracellular).

3. Concept of necrosis and apoptosis 4. The basic morphological evidence of necrosis (especially nuclear changes).

5. The basic morphological changes of main types of necrosis: coagulation, liquefaction, caseous necrosis and fibrinoid necrosis 1. THE CONCEPTS AND LESION OF ADAPTATION: ATROPHY, HYPERTROPHY, HYPERPLASIA, METAPLASIA ADAPTATION :: Within limits, most cells can adapt to environmental stresses by modifying their size/shape, pattern of growth, and/or metabolic activity.  Adaptation are classified into two types :: Physiological Changes hormones or endogenous chemical mediators (breast and uterus enlargement during pregnancy and breast feeding), exercise, etc

Pathological Changes cellular responses to modulate their structure and function to escape the injury or to be more resistant to the injury

ATROPHY It is a reduction in the size of an organ or tissue owing to either cell loss or a reduction in the size of cells. o normally formed → small o parenchyma cells of an organ EXAMPLES :: o atrophy of the brain in Alzheimer disease o thinning of the bones in osteoporosis.

Atrophy can be defined as Shrinkage in the size of the cell by loss of cell substance.

The common causes are ::       

Decreased workload (atrophy of disuse) Loss of innervation (denervation atrophy) Diminished blood supply Inadequate nutrition Loss of endocrine stimulation Aging (senile atrophy) Pressure PAGE 2

HYPERTROPHY It is an increase in the size of an organ or tissue owing to enlargement of constituent cells. It may be physiologic or pathologic.

EXAMPLES :: o cardium hypertrophy o pathological example :: the response of the heart and skeletal muscles to prolonged effort. o Physiologic hypertrophy :: Uterus during pregnancy HYPERPLASIA It is an increase in the size of an organ owing to an increased number of cells.

It can be induced by hormones ,growth factor or viruses EXAMPLES :: o hyperplasia of endometrium METAPLASIA It is the transformation of one mature tissue cell type into anotherEpithelium metaplasia Mesenchym metaplasia EXAMPLES :: o Epithelium metaplasia o Squamous metaplasia  Columnar epithelium Squamous epithelium  Ex :: BLADDER & CERVIX  Smokers often exhibit Sq. metaplasia  Vit. A deficiency or Overdose can lead to Sq. metaplasia o Glandular metaplasia  Where the tissue converts to a glandular form  Ex :: Barret esophagus

o Mesenchym metaplasia

PAGE 3

Tissue

Normal

Metaplasia

Stimulus

Airways

Pseudostratified columnar epithelium

Squamous epithelium

Cigarette smoke

Urinary bladder

Transitional epithelium

Squamous epithelium

Bladder stone

Esophagus

Squamous epithelium

Columnar epithelium

Gastro-esophageal reflux (Barrett's Esophagus)

Cervix

Glandular epithelium

Squamous epithelium

Low pH of vagina

2. THE MORPHOLOGICAL CHANGES OF INTRACELLULAR AND EXTRACELLULAR ACCUMULATION IN GROSS AND LIGHT MICROSCOPIC LEVELS: HYDROPIC DEGENERATION, FATTY CHANGE, HYALINE CHANGE (CONNECTIVE TISSUE, VASCULAR WALL, INTRACELLULAR).

HYDROPIC DEGENERATION (cell swelling) It refers to an increase in cell size due to increased intracellular accumulation of water. o Mild: clouding swelling o Severe: balloon-like change PAGE 4

Morphology   

NE: increasing weight and turgor of organs or tissues LM：cells are enlarged , crowded together, cytoplasm is translucent and stains more lightly EM: dilation of the endoplasmic reticulum, mitochondria swelling

FATTY CHANGE (fatty degeneration) It is the accumulation of triglyceride in the cytoplasm of parenchymal cells. o Sites：liver kidney myocardium Morphology 

NE:

 

o Acute Fatty Liver: Microvacuolar fatty change, foamy cytoplasm. o Chronic Fatty Liver: Macrovacuolar and microvacuolar fatty change. o frozen section + special stain SUDAN III--orange OIL RED O—red LM: The organ is enlarged and yellow, with a greasy appearance when cut EM: liposomes in the cytoplasm

HYALINE CHANGE (accumulation of proteins) Hyaline degeneration is applied to describe the material of homogeneous, glassy, usually eosinophilic appearance seen on microscopy of HE stain. 

Types :: o Hyaline of Connective Tissue o Hyaline of arteriolar walls o Intracellular hyaline

Hyaline of Connective Tissue 

GROSSLY：homogeneous pink hyaline appearance (e.g.,scar)  LM ： excessive collagen as thick hyalinized bands Hyaline of Arteriolar walls - Seen in benign hypertension 

LM : Deposition of amorphous proteinaceous material thickened of the wall narrowing of the lumen

Intracellular hyaline - Seen in hepatocyte, plasma cell, renal tubular cell, etc. 

Deposition of mass like proteinaceous material in the cells

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3. CONCEPT OF NECROSIS AND APOPTOSIS Cell death. There are two forms of cell death-necrosis,the ultimate result of irreversible cell injury, and apoptosis(programmed cell death) STIMULI PATTERN OF DEATH HISTOLOGY DNA BREAKDOWN CELLULAR PROCESSES TISSUE REACTION

NECROSIS Pathological Group

APOPTOSIS Physiological and Pathological Single cells

Swelling Random

Condensation Diffuse inter-nucleosomal

ATP depletion

Endonucleases

Inflammation

No

OR Cell Size Nucleus Plasma membrane Cellular contents Adjacent Inflammation Physiologic pathologic role

NECROSIS Enlarged (swelling) Pyknosis  Karyorrhexis  Karyolysis Disrupted Enzymatic digestion; may leak out of cell Frequent Invariably pathologic (culmination of irreversible cell injury)

APOPTOSIS Reduced (shrinkage) Fragmentation into nucleosome size fragments Intact; altered structure, especially orientation of lipids Intact; may be released in apoptotic bodies No Often physiologic, means of or eliminating unwanted cells; may be pathologic after some forms of cell injury, especially DNA damage

4. THE BASIC MORPHOLOGICAL EVIDENCE OF NECROSIS (ESPECIALLY NUCLEAR CHANGES).  



Necrotic cells show increased eosinophilia in hematoxylin and eosin stain.

Dead cells may be replaced by large, whorled phospholipid massed called myelin figure that are derived from damaged cell membranes.

Nuclear changes appear in 1 of 3 patterns, all due to nonspecific break down of DNA. 1) KARYOLYSIS [the basophilia of the chromatin may fade] 2) PYKNOSIS [characterized by nuclear shrinkage and increased basophila] 3) KARYORRHEXIS [the pyknotic or partially pyknotic nucleus undergoes fragmentation] PAGE 6

5. THE BASIC MORPHOLOGICAL CHANGES OF MAIN TYPES OF NECROSIS: COAGULATION, LIQUEFACTION, CASEOUS NECROSIS AND FIBRINOID NECROSIS Types of Necrosis a. Coagulative Necrosis b. Liquefactive Necrosis c. Fat Necrosis d. Caseous Necrosis e. Fibrinoid Necrosis f. Gangrene COAGULATIVE NECROSIS  

It typically caused by ischemia (infarct), is the most common form of necrosis.

The necrotic tissue appears pale and firm and retains its normal shape because no enzymatic lysis occurs--enzymes, like all other proteins, have been "coagulated" (i.e., inactivated). o occurs in solid organs, such as the kidney, heart ,spleen o deficient blood supply and anoxia o LM ::  The cell, devoid of its nucleus, appears as a mass of coagulated, pink-staining, homogeneous cytoplasm  the necrotic cell retains its cellular and structure outline, often for several days.

LIQUEFACTIVE NECROSIS  

It is typically found in the brain or in an abscess (i.e., a pusfilled cavity).

Tissue is softened ("liquefied") through the action of enzymes released from brain cells or, in the case of an abscess, polymorphonuclear neutrophils (PMNs). o brain following ischemia o suppurative inflammation o autolysis heterolysis

FAT NECROSIS  

It may be caused by trauma to adipose cells, or induced by lipolytic enzymes released during disease states (e.g., lipase release in acute pancreatitis).

Free fatty acids released from fat cells bind with calcium to form white specks composed of calcium soaps.

PAGE 7

Nonenzymatic Fat Necrosis

CASEOUS 

NECROSIS

It is typically seen in tuberculosis and certain fungal granulomas.

The tissue appears cheesy; histologically, it consists of granular material surrounded by epithelioid and multinucleated giant cells.



FIBRINOID NECROSIS 

It is typically seen in arteries, arterioles, or glomerular capillaries damaged by autoimmune diseases.

Blood vessels are impregnated by fibrin and other serum proteins and appear magenta-red in histologic sections.

It is characterized by loss of normal structure and replacement by a homogeneous, bright pink-staining necrotic material that resembles fibrin microscopically

 

GANGRENE 

Extensive tissue necrosis with putrefaction is complicated to a variable degree by secondary bacterial infection o foul-smelling gas o brown, green or black discoloration



TYPES

Dry gangrenes

Extremities ischemic necrosis

(“mummification”) refers to noninfected ischemic necrosis accompanied by drying of the the tissuse

Wet gangrene

extremities internal organs

It is a clinical term for ischemic necrosis accompanied by bacterial decomposition, which leads to partial liquefaction of the tissues.

Gas gangrene

clostridial species

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REVIEW Cellular adaptations to stress    

HYPERTROPHY : increased cell size and organ size ; occur in tissues incapable of cell division HYPERPLASIA : increased cell numbers ; occurs in tissues in which the cells are able to divide or contain tissue stem cells. Hyperplasia and hypertrophy may co-exist ATROPHY : decreased cell size or number and organ size METAPLASIA : replace one cell type by another cell type (reprogram tissue stem cells to differentiate into a new phenotype cell (phenotype change) PAGE 8



  

CELL INJURY OCCURS : 1) severe stress, cell cannot adapt ; 2) injurious stimuli affect many metabolic pathways and cellular organelles -leading to reversible injury or irreversible injury/cell death REVERSIBLE INJURY : in early stage or mild forms of injury, the functional and morphologic changes are reversible if the stress or stimulus is removed REVERSIBLE INJURY : cell swelling, fatty change, membrane bleeding, loss of microvilli, mitochondrial and ER swelling, eosinophilia (pink color) AMYLOIDOSIS :: a variety of fibrillary proteins (amyloid protein fibrils) deposited in interstitial tissues in certain pathologic conditions. o NE :: (yellowish to greyish discoloration )  small amounts undetectable  large amounts organ enlargement  pale gray and waxy o LM ::  HE it stains homogeneous pink  Congo red stain red  polarized light green o EM ::  branching fibrils 7.5 - 10 nm wide  On x-ray diffraction a pleated β-sheet structure resistant to enzymatic degradation

EXTRAS

-plasia and -trophy 

ANAPLASIA (structural differentiation loss within cell or group of cells)



APLASIA (organ or part of organ missing)



HYPOPLASIA (congenital below-average number of cells, especially when inadequate)



HYPERPLASIA (proliferation of cells)



NEOPLASIA (abnormal proliferation)



DYSPLASIA (change in cell or tissue phenotype)



METAPLASIA (conversion in cell type)



PROSOPLASIA (development of new cell function)



DESMOPLASIA (connective tissue growth)



ATROPHY (reduced functionality of an organ, with decrease in the number or volume of cells)



HYPERTROPHY (increase in the volume of cells)

PAGE 9

3 LECTURES

2. Tissue Repair TO MASTER 1. The following definitions: regeneration, repair and granulation tissue

REGENERATION Some tissues are able to replace the damaged components and essentially return to a normal state; this process is called regeneration.

REPAIR

Regeneration REPAIR

Scar healing GRANULATION TISSUE It is a kind of highly vascularized connective tissue Morphology NE: fresh, soft, pink and granular LM: ~ is composed of newly formed capillaries, proliferating fibroblasts, & residual inflammatory cells

QUESTIONS FROM LAB BOOK (Adaptation, Injury and Repair of Cell and Tissue) 1. Briefly discuss the gross and microscopic alterations associated with fatty change in the liver, heart and kidneys.

2. Distinguish between reversible and irreversible cell injury 3. Describe the main categories of necrosis, with examples.

4. Discuss the differences and similarities between the necrosis and apoptosis.

5. Under light microscopy, what portion of the cell would you expect to observe morphological changes of cellular death?

TERMS      

Atrophy Hypertrophy Metaplasia Hydropic degeneration Fatty degeneration of liver Hyaline degeneration PAGE 10

          

Calcification Coagulative necrosis Liquefactive necrosis Caseous necrosis Fibrinoid necrosis Gangrene Apoptosis Regeneration Repair Granulation tissue Collagenization

PAGE 11

5 LECTURES

3. Hemodynamic Disorder and Abnormalities of Blood Supply TO MASTER 1. The meanings or definitions of important terms in this chapter such as congestion, heart failure cell and thrombosis.

2. The concept, causes and morphologic characteristics of edema and describe ascites, hydrothorax and anasarca.

3. The concept, causes, pathological features and effects of congestion and describe the cause and pathological changes of liver and lung congestion.

4. The concept, etiology and pathogenesis of thrombosis (Virchow’s triad), and the type and consequences of thrombus. Compare the difference between thrombi and clots.

5. The concept and types of embolism and its influence on body.

6. The pathway of embolus travel. Name the most likely final destination of deep vein thrombosis.

7. The concept and types of infarction, and compare the morphological characteristics of various types of infarction.

1. THE MEANINGS OR DEFINITIONS OF IMPORTANT TERMS IN THIS CHAPTER SUCH AS CONGESTION, HEART FAILURE CELL AND THROMBOSIS. CONGESTION o A local increased volume of blood in a tissue may cause hyperemia or congestion. o Congestion is a passive process, resulting from impaired venous return from a tissue.

HEART FAILURE o Heart failure often called congestive heart failure. o Heart failure are of two types ::  RIGHT HEART FAILURE  Its mainly due to Hepatic venous congestion. They are of two types ::  Acute Hepatic Congestion :: the central hepatic veins and sinusoids are distended with blood, and there may be central hepatocyte degeneration.  Chronic Hepatic Congestion :: the central regions of hepatic lobules are grossly red-brown (due to cell death) and slightly depressed and are accentuated against surrounding zones of uncongested tan fatty liver (“nutmeg liver”)  LEFT HEART FAILURE  Its mainly due due to Pulmonary venous congestion. They are of two types ::

PAGE 12





Acute Pulmonary Congestion :: causes dilation of alveolar capillaries with transudation of fluid into the alveoli (pulmonary edema). Intra-alveolar hemorrhage may also result.

Chronic Pulmonary Congestion :: the septa become thickened and fibrotic and alveolar spaces may contain numerous hemosiderin-laden macrophages (“heart failure cells”)

THROMBOSIS Thrombosis is the formation of a blood clots inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot that breaks free and begins to travel around the body is known as an embolus.

2. THE CONCEPT, CAUSES AND MORPHOLOGIC CHARACTERISTICS OF EDEMA AND DESCRIBE ASCITES, HYDROTHORAX AND ANASARCA. EDEMA  Condition of excess fluid in the interstitial space.  CAUSE o A. Increase hydrostatic pressure  Localized venous obstruction, e.g. venous thrombosis, portal hypertension (ascites)  Generalized increased venous pressure, e.g. heart failure o B. Reduces plasma osmotic pressure  Low serum albumin, the serum albumin most responsible for maintaining colloid osmotic pressure.  - Excessive loss (nephritic syndrome, burns)  - Reduced synthesis (liver disease e. g. cirrhosis or protein malnutrition)

o C. Lymphatic obstruction  Usually localized; it can result from inflammatory or neoplastic obstruction. e.g.  Filariasis often causes massive lymphatic and lymph node fibrosis in the inguinal region (elephantiasis).  In breast cancer, radical operation can result in severe edema of the arm.

o D. Sodium and water retention  Increased salt, with the obligate accompanying water, causes increased hydrostatic pressure (due to expansion of the intravascular fluid volume) and diminished vascular colloid osmotic pressure.  poststreptococcal glomerulonephritis and acute renal failure.

PAGE 13

 MORPHOLOGY o Edema is easily recognized grossly. o ML: edema fluid generally is manifested only as subtle cell swelling, with clearing and separation of the extracellular matrix elements. o Edema is most commonly seen in subcutaneous tissues, lungs, and brain.  SUBCUTANEOUS EDEMA o Different distributions depending on the cause o Edema due to nephritic syndrome may be initially manifested in tissue with a loose connective tissue, such as the eyelids, causing periorbital edema. o Finger pressure over significantly edematous subcutaneous tissue displaces the interstitial fluid and leaves a finger shaped depression, so-called pitting edema.  PULMONARY EDEMA o Causes:Most frequently seen in left ventricular failure and other diseases (adult respiratory distress syndrome, renal failure). o Gross: lungs weight is increased, and they ooze fluid when cut o ML: dilation and congestion of capillaries, pale pink fluid in the alveoli  BRAIN EDEMA o Localized (abscesses or neoplasm) o Generalized (encephalitis or hypertensive crises) o Brain is grossly swollen with narrowed sulci and distended gyri showing signs of flattening against unyielding skull.

ASCITES Accumulation of fluid in the peritoneal cavity HYDROTHORAX It is a type of pleural effusion in which serous fluid accumulates in the pleural cavity.

ANASARCA It is an extreme generalized edema, is a medical condition characterized by widespread swelling of the skin due to effusion of fluid into the extracellular space.

3. THE CONCEPT, CAUSES, PATHOLOGICAL FEATURES AND EFFECTS OF CONGESTION AND DESCRIBE THE CAUSE AND PATHOLOGICAL CHANGES OF LIVER AND LUNG CONGESTION. Congestion is a passive process resulting from reduced outflow of blood from a tissue.

Cause :: Due to increased in hydrostatic pressure (refer above)

PAGE 14

4. THE CONCEPT, ETIOLOGY AND PATHOGENESIS OF THROMBOSIS (VIRCHOW’S TRIAD), AND THE TYPE AND CONSEQUENCES OF THROMBUS. COMPARE THE DIFFERENCE BETWEEN THROMBI AND CLOTS.

VIRCHOW’S TRIAD describes the three broad categories of factors that are thought to contribute to thrombosis.

1.

HYPERCOAGULABILITY

2.

HEMODYNAMIC CHANGES (STASIS, TURBULENCE)

3.

ENDOTHELIAL INJURY/DYSFUNCTION

Types of thrombi: 1. Pale thrombi (composed mainly of fibrin and platelets with a few erythrocytes) in the coronary and cerebral etc.

2. Red thrombi (Composed of platelets, fibrin and large numbers of erythrocytes) in the venous system.

3. Mixed thrombi (Consist of alternating layers of platelet aggregates) usually in veins.

4. Hyaline thrombi (Microthrombi is usually in DIC “Disseminated intravascular coagulation”).

5. Mural thrombi (In heart chambers or aortic lumen), 6. Occlusive (Coronary and cerebral arteries).

Site of thrombosis: 1. Arterial thrombosis; Occur after endothelial damage and local turbulence.

2. Cardiac thrombosis; Myocardial infarction, inflammation of cardiac valves, and turbulence and stasis in arterial chambers 3. Venous thrombosis; A. Thrombo-phlebitis (Occurs in the saphenous system ) B. Phlebo-thrombosis (Deep vein thrombosis “DVT”).

Evolution of thrombi: 1. Fibrinolysis via fibrinolytic system tPA (Small thrombi).

2. Organization and recanalization (Large thrombi).

3. Thrombo-embolism (Embolization).

DIFFERENCE BETWEEN THROMBUS AND CLOT THROMBUS

CLOT

INTRAvascular

Could be intra or extravascular

Has PLATELETS

LACKS Platelets

FIBRIN WBC – Lines of Zahn

No Lines of Zahn

PAGE 15

5. THE CONCEPT AND TYPES OF EMBOLISM AND ITS INFLUENCE ON BODY. 1. THROMBO-EMBOLISM  pulmonary and systemic arterial  SITE of arterial emboli (Brain , viscera such as renal, and upper and lower extremities).

2. AIR EMBOLISM  Occurs when enough air bubbles enter the vascular system.  CAUSES :: Trauma to internal jugular vein, child birth or abortion, blood transfusion.  CLINICAL EFFECT :: Air enters blood stream – Enter right ventricle – create a frothy mixture – obstruct circulation – cause DEATH.  It also obstruct pulmonary artery 3. NITROGEN GAS EMBOLISM  Decompression sickness;  (When air is breath at high pressure, increased amount of gas “particular nitrogen” become dissolved in blood and tissues).  CLINICAL EFFECT :: o ACUTE :: Bones causing pain [THE BENDS] and in the lungs causing the CHOCKES. o CHRONIC :: Avascular necrosis of bone 4.FAT EMBOLISM;  Occurs after truma involving fractures to the long bones.  CLINICAL EFFECT :: Respiratory insufficiency neurologic symptoms, anemia, petachia 5. AMNIOTIC FLUID EMBOLISM  With childbirth.

6. TUMOR EMBOLISM 

A mechanism of metastasis.

6. THE PATHWAY OF EMBOLUS TRAVEL. NAME THE MOST LIKELY FINAL DESTINATION OF DEEP VEIN THROMBOSIS. 1. PULMONARY EMBOLISM:  Pulmonary thromboembolism is very common.  Most common source (90%) is from the leg veins (phlebothrombosis).  Thrombi in pelvic venous plexuses are less common source.  The size of the embolus is the factor most influencing the clinical effects of pulmonary embolism.  Massive emboli (5%): Sudden death; Large emboli may lodge in the outflow tract of the right ventricle or in the main pulmonary artery.  Medium-sized emboli (10%): Emboli lodge in an end artery, and secondary blood supply from the bronchial arteries must be compromised (by preexisting cardiopulmonary disease), Pulmonary infarction.  Small emboli (85%): No symptoms; Common result, thrombus undergoes lysis and resolution.

Develop pulmonary hypertension in 2~4% of patients.

PAGE 16

2. SYSTEMIC ARTERIAL EMBOLISM:  Sources of arterial emboli: 1. infective endocarditis with vegetations on valves; 2. mural thrombus in myocardial infarction; 3. left atrial thrombus in atrial fibrillation; 4. mural thrombi in aortic and ventricular aneurysms; 5. thrombus in atherosclerotic plaques.  SITES: Brain--causing a stroke; Viscera--renal, mesenteric, and splenic; Upper and lower extremities 3. DVT JOURNEY:  Fragmented thrombi from DVTs are carried through progressively larger channels and usually pass through the right side of the heart before arresting in the pulmonary vasculature.

7. THE CONCEPT AND TYPES OF INFARCTION, AND COMPARE THE MORPHOLOGICAL CHARACTERISTICS OF VARIOUS TYPES OF INFARCTION. INFARCTION is the development of the area of necrosis in an organ or tissue resulting from sudden reduction of its blood supply. Always caused by atrial occlusion.

1. Pale or anemic infarcts; (Kidney, brain, spleen and heart) appear slightly darker and wedgeshaped area, becoming soft, pale, and tan-yellow.

2. Red or hemorrhagic infarcts; (Caused by venous occlusion in loose tissues such as lung and intestine) appear deep red, firm and sharply demarcated area.

3. Sterile infarcts v/s septic infarcts (Infects are by secondary bacterial infection of the necrotic tissue) 4. Venous infarction; (Results when total occlusion of all venous drainage from a tissue occurs) e.g.:: sagittal sinus and renal vein , and always hemorrhagic.

QUESTIONS FROM LAB BOOK 1. What is the difference between a thrombus and an embolus? What is an infarct?

2. What are the components of Virchow’s triad and how to do they cause thrombosis?

3. What is the major complication of thrombus in a leg vein?

4, What are the effects of intra-cardiac thrombi?

5. What coagulation disturbances may be encountered in patients with tumors?

6. What is the difference between a pulmonary embolus and pulmonary infract?

Terms       

Congestion Heart failure cell Nutmeg cell Thrombosis Embolism Infarction Brown duration of lungs

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6 LECTURES

4. Inflammation TO MASTER 1. The meanings or definitions of important terms in this chapter, such as abscess, adhesion molecules and granuloma.

2. The concept, basic pathological changes and consequences of inflammation. Name four cardinal signs of inflammation.

3. Process of chemotaxis, opsonization and phagocytosis.

4. The types of inflammation and pathological changes of different types of inflammation.

Describe the morphological characteristics and possible outcomes of the fibrinous and purulent inflammations.

5. The causes and morphological characteristics of chronic inflammation including granuloma

1. Definitions of :: a) ABSCESS •

A localized collection of purulent inflammation accompanied by liquefactive necrosis, sometimes surrounded fibrovascular tissue, is referred to abscess.

•

Caused by STAPHYLOCOCCUS AUREUS

b) ADHESION MOLECULES Cell adhesion molecules (CAMs) are proteins located on the cell surface involved in binding with other cells or with the extracellular matrix (ECM) in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. c) GRANULOMA **** GRANULOMATOUS INFLAMMATION: A special type of chronic inflammation, is characterized by the formation of granuloma defined as an aggregate of macrophages.

2. The concept, basic pathological changes and consequences of inflammation. Name four cardinal signs of inflammation.  Inflammation: Inflammation is a complex reaction to injurious agents that consists of vascular response, cellular reaction, and systemic reactions.  Systemic changes which includes :: (A) Fever and others (B) Changes of the peripheral white blood cell count (C) Changes in plasma protein levels.  The main components of inflammation are a vascular reaction and a cellular response; both are activated by mediators derived from plasma proteins and various cells.  The steps of the inflammatory response can be remembered as: (1) recognition of the injurious agent, (2) recruitment of leukocytes, (3) removal of the agent,

PAGE 18

(4) regulation (control) of the response, (5) resolution (repair).

 The outcome of acute inflammation is either elimination of the noxious stimulus, followed by decline of the reaction and repair of the damaged tissue, or persistent injury resulting in chronic inflammation

CARDINAL SIGNS OF INFLAMMATION ARE :: • Redness • Heat • Swelling • Pain 3. Process of chemotaxis, opsonization and phagocytosis.

CHEMOTAXIS: • Directed migration of leukocyte towards chemical stimulus • Margination  Emigration  Margination

OPSONIZATION:  Phagocytosis include 3 stages. Opsonisation comes under recognition and attachment.  Enhanced by opsonins, opsonin receptors on leukocytes.  Without opsonins, macrophage can bind bacteria via pattern recognition receptors

PHAGOCYTOSIS.

1. Recognition and attachment 2. Engulfment 3. Microbial killing 4. The types of inflammation and pathological changes of different types of inflammation.

Describe the morphological characteristics and possible outcomes of the fibrinous and purulent inflammations.

Inflammation is classified into acute and chronic inflammation.  Acute inflammation Acute inflammation is of relatively short duration, lasting from a few minutes up to a few days, and is characterized by fluid and plasma protein exudation and a predominantly neutrophils accumulation.  Chronic inflammation is of longer duration (days to years) and is typified by influx of lymphocytes and macrophages with associated vascular proliferation and scarring.

Acute inflammation has two major events which are vascular response and cellular response.



Some types of Acute inflammation are: ⁻ Serous inflammation PAGE 19

⁻ Fibrinous inflammation ⁻ Suppurative inflammation ⁻ Hemorrhagic inflammation.

1) SEROUS INFLAMMATION •

• •

Characterized by accumulation of excessive clear watery fluid with a variable protein content, which implies increased vascular permeability.

Occurring in skin (burn blisters), and in peritoneal, pleural and pericardial cavities Catarrhal inflammation

2) FIBROUS INFLAMMATION •

•

Large amounts of fibrinogen pass the vessel wall, and fibrins are formed in the extracellular spaces, e.g. fibrinous pericarditis or pleuritis.

Excessive fibrinous exudation usually lead to organization and fibrosis in the affected area.

Cor villosum

Pseudomembraneous inflammation • Pseudo-membranous inflammation is the fibrinous inflammation occurred on a mucosal surface, and consists mainly of fibrin mixed with necrotic cells on the surface of the affected mucosa, e.g. diphtheria, bacillary dysentery.

Diphtheria

3) SUPPURATIVE INFLAMMATION • •

• •

Infiltration of neutrophils is dominated.

Characterized by the production of pus, usually caused by infection with pyogenic bacteria such as Staphylococcus aureus and Streptococcus pyogenes.

Pus is made up of neutrophils, necrotic cells and edema fluid.

Abscess :: A localized collection of purulent inflammation

Purulent meningitis

accompanied by liquefactive necrosis, sometimes surrounded fibrovascular tissue, is referred to abscess.

Caused by Staphylococcus aureus. Eg:: abscess in brain, Renal abscess

•

Sinus tract and Fistula :: Deep-seated abscesses sometimes discharge their pus along a sinus tract (an abnormal connection between the abscess and the skin or a mucosal surface).

4) HEMORRHAGIC INFLAMMATION •

•

Obvious hemorrhage occurs when the blood vessels in the inflamed areas are severally injured.

In some infections diseases, e.g. endemic hemorrhagic fever, Ebola virus disease, leptospirosis and plague.

5. The causes and morphological characteristics of chronic inflammation including granuloma 



Characteristics of Chronic Inflammation ************************* • Infiltration with chronic inflammatory cells • Tissue destruction • Repair: angiogenesis and fibrosis According to Granulomatous inflammation Chronic inflammation classified into • epithelioid cell granuloma, which represents an immune response in which the macrophages are activated by lymphokine of stimulated T cells PAGE 20

•

foreign body granuloma, which represents nonimmune phagocytosis of foreign nonantigenic material by macrophages.

Features of classification o Activated macrophages (epithelioid cells) aggregate to form granulomas surrounded by lymphocytes, plasma cells, fibroblasts. o Epithelioid cells appear on microscopic examination as large cells with abundant pale, foamy cytoplasm. o Granulomas commonly contain multinucleate giant cells--Langhans' giant cell, foreign body giant cell --formed from the fusion of many macrophages.

QUESTIONS FROM LAB BOOK 1. What is the inflammatory reaction? What are the clinical manifestation?

2. What are mediators of inflammation? How do they function?

3. What are the key differences between acute and chronic inflammation.

TERMS                 

Pseudomembranous inflammation Ulcer Abscess Phlegmonous inflammation Sinus Fistula Catarrhal inflammation Adhesion molecule Granuloma Granulomatous inflammation Inflammatory polyp Inflammatory pseudo-tumor Inflammatory mediator Chemokine Villus heart Exudate Cytokines

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12 LECTURES

6. & 9. Neoplasia and the Malignancies of Hematopoietic and Lymphoid Systems.

TO MASTER 1. The meanings or definitions of important terms in this chapter, such as atypia, anaplasia and dysplasia.

2. Concept and morphological characteristics of neoplasm.

3. The general principles of neoplastic nomenclature and classification. List the common exceptions to standard terminology.

4. The growth and spread of neoplasm. Master the main routes of metastasis. Learn the mechanism of local intervention.

5. The grading and staging of tumors on body.

6. The difference between benign and malignant tumors.

7. The difference between carcinoma and sarcoma.

4. The meanings or definitions of important terms in this chapter, such as ATYPIA, ANAPLASIA & DYSPLASIA. ATYPIA Structural abnormality of a cell ANAPLASIA • Lack of histologic differentiation.

• Anaplastic tumor is not clear its tissue of origin.

• It is only used in the malignant neoplasms.

DYSPLASIA • The term dysplasia is used to describe disorder but non-neoplastic proliferation of epithelium.

• Loss of normal orientation.

• Loss of cellular uniformity, exhibiting pleomorphism, deeply stained nuclei, a high nuclear to cytoplasmic ratio, an increased number of mitoses.

OR • [atypical hyperplasia or metaplasia] is a premalignant transformation of normal epithelia.

5. Concept and morphological characteristics of NEOPLASM. • A neoplasm can be defined as an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists after the initiating stimulus has been removed.

• Fundamental to the origin of all neoplasms is loss of responsiveness to normal growth controls.

• Neoplasms are divided into two main groups: I) BENIGN NEOPLASM grow slowly and remain localized to the site of origin.

II) MALIGNANT NEOPLASM grow rapidly and may spread widely.

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Characters of tumors • Progressive: lose control • Purposeless: no useful • Parasitic: at the expense of body Structure Characteristics of Tumours • Gross appearance: benign vs malignant • Colour and consistency: benign vs malignant • Firmer: usually firmer than surrounding tissue, proportion of parenchyma & stroma • Border: Benign and malignant Histological Structure of Tumors • All tumors, benign and malignant, have two basic components : • Parenchyma :: neoplastic cells from which the tumor derives • Stroma :: connective tissue, blood vessels, lymphatics that supply blood and provides support for the growth of parenchymal cells.

3. The general principles of NEOPLASTIC NOMENCLATURE and CLASSIFICATION. List the common exceptions to standard terminology.

NOMENCLATURE PRINCIPLES • Base on • Histogenesis :: gives information about the type of cell from which the tumor has arisen • Behavior :: behavior gives information on whether the cell is benign or malignant CLASSIFICATION a. BENIGN TUMORS ⁻ These are generally named after the cell of origin followed by the suffix -oma ⁻ Such as :: Fibroma, chondroma etc ⁻ The nomenclature of benign epithelial neoplasms is more complex. ⁻ Eg:: adenoma, villus or tubular adenomas, papillary cystadenoma, papillaoma b. MALIGNANT TUMORS CARCINOMA SARCOMA 

Malignant epithelial neoplasm



Malignant mesenchymal neoplasm



Epithelial  ROOT + CARCINOMA



Epithelial  ROOT + SARCOMA



Ex :: Fibrosarcoma, Chondrosarcoma



Ex :: squamous carcinoma, adenocarcinoma EXCEPTION OF THESE RULES A. Sound benign but are really malignant  

Lymphoma Plasmacytoma PAGE 23

 

Melanoma Seminoma

B. Blastoma  Derived from primitive tissue  Malignant :: Meuroblastoma, Nephroblastoma etc  Benign :: Osteoblastoma, Chondroblastoma C. Leukemia  Malignant D. Teratoma  Mature teratoma vs Immature teratoma E. Eponymously named tumors      

Ewing sarcoma Kaposi sarcoma Hodgkin lymphoma Burkitt lymphoma Wilms tumor (nephroblastoma) All of malignant tumors above Examples of tumor nomenclature HISTOLGICAL TYPE

BENIGN

MALIGNANT

EPITHELIAL TUMORS *Glandular

Adenoma

Adenocarcinoma

* Non-glandular, e.g:

Papilloma

Carcinoma

Squamous cell

*Squamous cell papilloma

*Squamous cell carcinoma

Transitional cell

*Transitional cell papilloma

*Transitional cell carcinoma

Basal cell

*Basal cell papilioma

*Basal cell carcinoma

Adipose Tissue

Lipoma

Liposarcoma

Cartilage

Chondroma

Chondrosarcoma

Bone

Osteoma

Osteosarcoma

Smooth muscle

Leiomyoma

Leiomyosarcoma

Voluntary muscle

Rhabdomyoma

Rhabdomyosarcoma

Blood vessels

Angioma

Angiosarcoma

HAEMOPOIETIC TUMOR

---

Leukaemia

LYMPHORETICULAR TUMOR

---

Lymphoma

MELANOCYTES

---

Malignant melanoma

GERMINAL CELL TUMOR

Benign teratoma

Malignant teratoma

CONNECTIVE TISSUE TUMORS

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4.

The GROWTH and SPREAD of neoplasm. Master the MAIN ROUTES OF METASTASIS. Learn the mechanism of local intervention.

The rate of proliferation of neoplastic cells varies :: GROWTH (a) BENIGN TUMOR • Exophytic • Circumscribed • Encapsulated (b) MALIGNANT TUMOR • Endophytic • Ulceration • Non – encapsulated Modes of spread :: (a) Local invasion (b) Malignant Main Routes :: (a) Lymphatic :: from secondary tumors in lymph nodes (b) Vascular :: from secondary tumors in organs (c) Transcoelomic :: in plural, peritoneal & Pericardial cavities Mechanism :: (a) Detachment of tumor cells from each other, E-Cadherins (b) Degeneration of ECM, MMP (c) Attachment of tumors of ECM via Integrins (d) Migration of tumor cells, Motility factors, HGF

5.

The GRADING and STAGING of tumors on body.

• Only used in malignant tumors • It help clinicians to determine the prognosis for the patient.

GRADING • The grade is determined by a pathologist who examines the tumor histologically.

• Cancers are classified as grades I to IV with increasing anaplasia.

• GRADES I: WELL DIFFERENTIATED • GRADES II: MODERATELY DIFFERENTIATED • GRADES III: POORLY DIFFERENTIATED • GRADES IV: UNDIFFERENTIATED

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STAGING / TNM SYSTEM • The stage is determined by the extent of spread of a cancer within the patient.

• Clinically • T: SIZE OF PRIMARY TUMOR  T1, T2, T3, and T4 describe the increasing size of the primary tumor.

• N: REGIONAL LYMPH NODE INVOLVEMENT  N0, N1, N2, and N3 indicate progressively advancing lymph node involvement.

• M: METASTASES  M0 and M1 reflect the absence or presence of distant metastases.

6.

The difference between BENIGN and MALIGNANT TUMORS.

Comparison of benign & malignant tumors BENIGN TUMOR

MALIGNANT TUMOR

GROWTH RATE

Slow

Rapid

CHARACTER OF GROWTH

Expansion

Infiltration

TUMOR SPREAD

Remains localized

Metastasis by bloodstream and lymphatics PAGE 26

CELL DIFFERENTIATED

7.

Well differentiated

Poorly differentiated

The difference between CARCINOMA and SARCOMA.

Principal characteristics of carcinomas and sarcomas Features

CARCINOMA

SARCOMA

ORIGIN

Epithelium

Connective tissues

BEHAVIOUR

Malignant

Malignant

FREQUENCY

Common

Relatively rare

PREFERRED ROUTE OF METASTASIS

Lymph

Blood

IN SITU PHASE

Yes

No

AGE GROUP

Usually over 50 years

Usually below 50 years

EXTRAS  LYMPHOMA, TERATOMA, MELANOMA Lymphoma :: Malignant neoplasm in lymph nodes Teratoma :: Orginates from germs cell. Eg: gonads Melanoma :: also called Malignant melanoma, occurs in fair skinned people living in sunny climate Etiological agent :: UV light  HODGKIN and NON HODGKIN LYMPHOMAS HODGKIN LYMPHOMA

NON-HODGKIN LYMPHOMA

Single Axial group of Nodules

Multiple peripheral Nodes

Contagious spread

Non contigious spread

Mesenteric Nodes & Waldeyer ring rarely involved

Both involved

Extra-nodal involvement uncommon

Common

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LEIOMYOMA vs LEIOMYOSARCOMA

 CELLULAR ADAPTATIONS Increase in size of parenchymal cells resulting in enlargement of organs Eg :: Hypertrophy of cardiac muscle Reduction of number & size of parenchymal cells of an organ or its parts which once normal Eg :: Ischemic atrophy Neuropathic atrophy

Reversible changes in one type of epithelial or mesenchymal adult cell to another type of epithelial or mesenchymal adult cell.

Increased number of parenchymal cells resulting in enlargement of the organ.

Eg :: wound healing

Disordered cellular development (pleomorphism, nuclear hyperchromasia, mitosis, loss of polarity) accompanied with metaplasia and hyperplasia

Epithelial  Squamous and Columnar metaplasia Mesenchymal  Osseous and Cartilaginous metaplasia

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LAB BOOK QUESTIONS 1. How are tumors named ? What are the common prefixes used in naming tumors? How would you name the following tumors: a benign tumor of fat, a malignant tumor of muscle, a malignant tumor of squamous epithelium, a benign tumor of glandular epithelium arising from the surface of the colon and projecting into the lumen, a malignant tumor of cartilage ?

2. What are the major differences between a benign and a malignant tumor?

3. What is a lymphoma? What is a teratoma? What is a melanoma?

4. What is leukemia? What are its major clinical manifestations?

5. What are oncogenes and tumor suppressor genes?

Terms ::  Atypia Structural abnormality in a cell  Anaplasia Lack of histological differentiation, malignant neoplasm, not clear its tissue orgin 

Dysplasia Premalignant transformation of normal epithelia



Direct spread



Transcoelomic metastasis



Carcinoma in situ



Cachexia :: Wasting syndrome is loss of weight, muscle atrophy, fatigue, weakness



Paraneoplastic syndrome In some patients cancer produces remote symptoms that are not explained by local effects of tumour or metastatis.



Teratoma Orginates from germ cells. Eg :: Gonads



Oncogene Mutated form of proto oncogenes, positive regulators of cell growth.



Tumor suppressor gene Negative regulators of cell growth.



Two Hit Hypothesis TSG recessive, Both of the Normal alleles must be inactivated for the development of cancer



Warburg effect <asked for 2012 batch> Cancer cell obtain most of their energy from glucose using glycolytic pathways rather than from the oxidative breakdown of pyruvate in mitochondria.

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