Systemic pathology new (updated) by Medicos 143

PATHOLOGY

BHAGATH M S

2013 batch

S Y S T E M I C

R E V I E W

CREDIT 7

RAJEEV BISWAS

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C O N T E N T

B. SYSTEMIC PATHOLOGY 6

Disease of Cardiovascular System

8 LECTURES

Disease of Respiratory System

6 LECTURES

Disease of Digestive System

9 LECTURES

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

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6. DISEASES OF CARDIOVASCULAR SYSTEM

8 LECTURES

EXAM PATTERN :: 2-3 TERMS, 1 QUESTION TO MASTER 1. The pathologic character of atherosclerosis. 2. The location and frequencies of coronary atherosclerosis. 3. The morphological features and complications of myocardial infarction. 4. The clinical features, the gross and microscopic morphology, and the complications of hypertension including the heart, central nervous system, kidneys, blood vessels. 5. The basic pathological changes of rheumatism. 6. The pathological character of rheumatic pancarditis including endocarditis, myocarditis and pericarditis. 7. The gross and microscopic morphology, clinical presentation and course of infective endocarditis. 8. The definition of atherosclerosis, fatty streaks, artheromatous plaque, myocardial infarction, ventricular aneurysm, hypertension, concentric hypertrophy, coronary heart disease, Aschoff body, rheumatic vegetation, chronic rheumatic heart disease, mitral stenosis, infective endocarditis.

1. 1. 2. 3.

THE PATHOLOGIC CHARACTER OF ATHEROSCLEROSIS. Fatty Streak Fibrious atheromatous plaque Complicated plaque

FATTY STREAK  Collection of foam cells in the intima FIBRIOUS ATHEROMATOUS PLAQUE  Fibrous cap  Lipid zone  Basal zone COMPLICATED PLAQUE  Thrombosis  Dystropic calcification  Ulceration  Vascularization  Hemorrhage  Aneurysms 2. THE LOCATION AND FREQUENCIES OF CORONARY ATHEROSCLEROSIS. (Coronary ATH is narrowing of the lumina of the coronary artery and accounts for the vast majority of coronary artery disease, and is most marked in the proximal parts of the coronary arteries.)

The location and frequencies of coronary ATH in the right and left main coronary arteries are in turn as follows: (1)left anterior descending coronary artery(40%-50%) (2)right coronary artery(30%-40%) (3) left circumflex coronary artery(15%-20%) The obstructive degree of the lumen of the coronary artery is divided into 4 grades :: 3|Page

GRADE I < 25% GRADE II 26 – 50 % GRADE III 51 – 75 % GRADE IV ≥ 75% 3. THE MORPHOLOGICAL FEATURES AND COMPLICATIONS OF MYOCARDIAL INFARCTION. TIME

GROSS

0 – 30 min

No change

No change [EM :: Reversible changes (Mitochondrial swelling)]

1 – 2 hours

No change

Few wavy fibers at the margin of infarct [EM :: Irreversible changes (Sarcolemmal disruption, Electron dense mitochondrial deposits)]

4 – 12 hours

No change

Early coagulative necrosis, edema, occasional neutrophils

18 – 24 hours

Slight Pallor (pale appearence) or mottling

Continuing coagulative necrosis [nuclear pykinosis, cytoplasmic eosinophilia], neutrophilic infiltrate “contraction band” necrosis.

25 – 72 hours

Pallor

Complete coagulative necrosis of myofibers, heavy neutrophil infiltrate

4 – 7 days

Central Pallor with hyperemic border

Macrophages appear, early disintegration of necrotic fibers, granulation tissue at the edge of the infarct.

10 days

Max yellow, soft, shrunken, purple border

Well developed phagocytosis, prominent granulation tissue, peripheral areas of infarct.

7 – 8 weeks

Firm, gray

Fibrosis

COMPLICATIONS A: arrhythmias B: left ventricular failure C: progressive infarction D: pericarditis E: systemic embolism from mural thrombi F: myocardial rupture G: ventricular aneurysm

4. THE CLINICAL FEATURES, THE GROSS AND MICROSCOPIC MORPHOLOGY, AND THE COMPLICATIONS OF HYPERTENSION INCLUDING THE HEART, CENTRAL NERVOUS SYSTEM, KIDNEYS, BLOOD VESSELS. a) EARLY HYPERTENSION - The early phase hypertension is asymptomatic, and diagnosis can be made only by detecting the elevation of blood pressure. b) HYPERTENSIVE HEART DISEASE - The term hypertensive heart disease is used when the heart is enlarged in the absence of a cause other than hypertension. - CONCENTRIC HYPERTROPHY - Left ventricular hypertrophy and normal size of the chamber. - With long – standing and severe hypertension left ventricular dilation and failure occurs.

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c) HYPERTENSIVE RENAL DISEASE - Changes in renal arterioles occur in most cases of hypertension, resulting in decreased glomerular filtration rate, progressive fibrosis and loss of nephrons in kidney. - Renal failure with elevation of serum creatinine usually occurs only in patients with malignant hypertension. d) HYPERTENSIVE CEREBRAL DISEASE - Hypertensive patients have a greatly increased incidence of cerebrovascular disease, both thrombosis and hemorrhages (strokes). e) HYPERTENSIVE RETINAL DISEASE - Narrow, irregular arteries with thickened walls characterize mild to moderate hypertension. 5. THE BASIC PATHOLOGICAL CHANGES OF RHEUMATISM. a) EARLY PHASE [Exudative, degeneration] - The initial tissue reaction is that of focal fibrinoid necrosis. b) PROLIFERATIVE PHASE [Granulomatous phase] - The hallmark of acute rheumatic carditis is the presence of multiple foci of inflammation within the connective tissue of heart called Aschoff bodies. c) FIBROSIS PHASE [Healed phase] - The Aschoff body is fusiform, the cytoplasm of the component cell is diminished in amount and the cells become spindle shaped. The collagenous fibers fuse to small scars. 6. THE PATHOLOGICAL CHARACTER OF RHEUMATIC PANCARDITIS INCLUDING ENDOCARDITIS, MYOCARDITIS AND PERICARDITIS. ENDOCARDITIS (valvulitis) - Involved valves show edema and denudation of the lining endocardium, particularly in areas of free edge of the value. - Platelet â&#x20AC;&#x201C; Fibrin thrombi [Rheumatic vegetations] form in areas of endocardial damage. MYOCARDITIS - Acute myocardial involvement, characterized by the presence of numerous Aschoff bodies in the myocardium, causes tachycardia and dilation of the heart. PERICARDITIS - Acute inflammation of the pericardium (fibrinous pericarditis) occurs only in severe cases, causing chest pain and a pericardial rub.

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7. THE GROSS AND MICROSCOPIC MORPHOLOGY, CLINICAL PRESENTATION AND COURSE OF INFECTIVE ENDOCARDITIS. a) ACUTE INFECTIVE ENDOCARDITIS - Acute course - Virulent agents infect normal valves. - Characterized by severe destruction of the valve or abscess. b) SUB-ACUTE INFECTIVE ENDOCARDITIS - Chronic course - Less Virulent agents infect abnormal valves. - Not Characterized by severe destruction of the valve or abscess. PATHOLOGY ⁻ Infected thrombi (vegetations) are the characteristic pathologic finding in infective endocarditis. ⁻ The hallmark of infective endocarditis is the presence of valvular vegetations containing bacteria or other organisms. ⁻ The vegetations are multiple, large ,and friable and commonly become detached from the valve as emboli. CLINICAL FEATURES A) BACTEREMIA [or fungemia] :: Petechial hemorrhages, Miliary abscesses B) IMMUNE COMPLEXES :: Focal or diffuse proliferative glomerulonephritis, Cutaneous immune complex-mediated vasculitis C) VALVULAR DYSFUNCTION :: Cardiac murmurs, Valve perforation D) EMBOLISM :: Infarction of many organs 16. THE DEFINITION OF ATHEROSCLEROSIS (ATH) ATH is a disease of large and medium-size arteries that results in progressive accumulation within the intima of SMCs, lipids and connective tissue. FATTY STREAKS  They are thin, flat, yellow streaks in the intima consists of macrophages and SMCs.  Collection of foam cells in intima ARTHEROMATOUS PLAQUE o > It’s the basic lesion of clinical ATH. o > It consist of 3 zones ::  Fibrous cap  Lipid zone  Basal zone 6|Page

MYOCARDIAL INFARCTION Myocardial infarction (MI) is refers to a discrete focus of ischemic necrosis in the heart Acute myocardial infarction  Heart attack

VENTRICULAR ANEURYSM High intraventricular pressure may cause progressive outward bulging of the area of the infarction during systole. This paradoxical motion of part of the ventricular wall is called ventricular aneurysm.

HYPERTENSION A persistent elevation of Blood pressure to greater than 140mm µg systolic, greater than 90mm µg diastolic or both. CONCENTRIC HYPERTROPHY  Left ventricular hypertrophy and normal size of the chamber.  With long-standing and severe hypertension, left ventricular dilation and failure occurs.

CORONARY HEART DISEASE Coronary heart disease is one of ischemic heart disease (IHD) that is ,in the vase majority of cases, a consequence of ATH of the coronary arteries and develops when the flow of blood is inadequate to provide for the oxygen demands of the heart. Four syndromes :: 1. 2. 3. 4.

Various forms of angina pectoris (chest pain) Acute myocardial infarction Sudden cardiac death Chronic IHD with congestive heart failure

ASCHOFF BODY The Aschoff body is fusiform ,the cytoplasm of the component cell is diminished in amount, and the cells become spindle shaped. The collagenous fibers fuse to small scars.

RHEUMATIC VEGETATIONS Platelet- Fibrin Thrombi [Rheumatic vegetations] form in areas of endocardial damage.

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CHRONIC RHEUMATIC HEART DISEASE  Rheumatism is a multisystem inflammatory disease that follows an episode of group A streptococcal infection after an interval of a few weeks.  Rheumatism may cause heart disease, carditis, polyarthritis, and so on.  It is proposed that antibodies directed against the M proteins of group A streptococci crossreact with normal proteins present in the heart, joints, and other tissues. MITRAL STENOSIS A valvular heart disease characterized by narrowing orifice of mitral valve of the heart.

INFECTIVE ENDOCARDITIS Infective endocarditis is an infection associated with formation of an adherent, bulky mass of thrombotic debris ,and organisms, termed some vegetations on the endocardial surface, usually on a valve.

QUESTIONS FROM LAB BOOK 1. How to differentiate the vegetations of rheumatic endocarditis and bacterial endocarditis ? 2. Terms  Aschoff body.  Concentric hypertrophy.  Atheroma.  Fibrous atheromatous plaque. EXTRAS 1. CORONARY HEART DISEASE Coronary heart disease is one of ischemic heart disease (IHD) that is ,in the vase majority of cases, a consequence of ATH of the coronary arteries and develops when the flow of blood is inadequate to provide for the oxygen demands of the heart. Four syndromes: (1)various forms of angina pectoris (chest pain) (2)acute myocardial infarction (MI) (3)sudden cardiac death (4)chronic IHD with congestive heart failure

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7. DISEASES OF RESPIRATORY SYSTEM

6 LECTURES

EXAM PATTERN :: 2 TERMS, 1 SHORT (from respiratory/endocrine) TO MASTER 1. The etiology, pathological features, complications and the clinical features of lobar pneumonia, lobular pneumonia and viral pneumonia. 2. The definition of acute interstitial pneumonia. 3. The definition of COPD. 4. The pathological features, complications and clinical features of chronic bronchitis,emphysema, bronchial asthma, bronchiectasis and silicosis. 5. The etiology, pathogenesis and pathological features of chronic cor pulmonale. 6. The etiology, classification, gross types, spread and clinical features of carcinoma of the lung. 7. The definition of condolidation, acute congestion, red hepatization, gray hepatization, bronchopneumonia, interstitial pneumonia, emphysema, panacinar emphysema, centriacinar emphysema, periacinar emphysema, bullous emphysema, bronchiectasis, chronic obstructive pulmonary disease, chronic bronchitis, asthma and silicosis.

1. THE ETIOLOGY, PATHOLOGICAL FEATURES, COMPLICATIONS AND THE CLINICAL FEATURES OF LOBAR PNEUMONIA, LOBULAR PNEUMONIA AND VIRAL PNEUMONIA. LOBAR PNEUMONIA It is a type of acute bacterial pneumonia. The bronchi are not involved and large confluent areas are consolidated. Etiology :: ⁻ It typically occurs with primary pneumonias caused by virulent agents, mostly pneumococci. ⁻ The most common cause of air space pneumonia is Streptococcus pneumoniae. ⁻ This is overwhelmingly the case ( 60% - 70% )in primary communityacquired pneumonias of lobar pattern, with most of the remainder resulting from Legionella Pneumophila. ⁻ It is increased frequency in three groups of individuals: (1) Those with underlying chronic diseases such as CHF, COPD, or diabetes. (2) Those with either congenital or acquired immunoglobulin defects. (3) Those with decreased or absent splenic function. Pathological features :: Lobar pneumonia progresses through 4 stages :: 1. ACUTE CONGESTION :: Dilation of alveolar capillaries and early fluid exudation, few neutrophil emigration and erythrocytes diapedesis into the alveoli. 2. RED HEPATIZATION :: Exudation and neutrophil emigration. Alveolar congestion is still present, and the alveolar air has been replaced by the cellular exudate, erythrocytes, neutrophils & fibrin. 3. GRAY HEPATIZATION :: Neutrophil emigration, Fibrin exudates persist within the alveoli. 4. RESOLUTION :: Resorption of exudate and enzymatic digestion of inflammatory debris. Clinical features :: It is the evidence of consolidation, auscultation sound, tactile fremitus enhancement.

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LOBULAR PNEUMONIA (BRONCHIOPNEUMONIA) It a type of acute bacterial pneumonia. The bronchi are infected, with involvement of adjacent alveoli in a patchy often limited fashion. Etiology: it is secondary pneumonia due to many bacteria, staphylococcus aureus, gram negative bacteria, streptococcus pneumoniae, hemophilus influenza. Pathologic features: ⁻ characterized by foci of acute suppurative inflammation centered on bronchioles. ⁻ The consolidation may be patchy through one lobe but is more often multilobar & frequently bilateral & basal. ⁻ Well-developed lesions are slightly elevated, dry, granular, gray-red to yellow, and poorly delimited at their margins. ⁻ Edema not involved normaly. Histologically, suppurative exudate in bronchi, bronchioles, and adjacent alveolar spaces. ⁻ Neutrophils dominant. Abscesses are marked by necrosis of underlying architecture. Clinical features: ⁻ The onset is insidious, course is irregular worsening of the patient's prior condition. ⁻ Low-grade fever and cough productive of purulent sputum resolution usually occurs. Patient is not severly debilitated. Complication: ⁻ disturbances of ventilation and perfusion ⁻ pleural invovlement ⁻ bacteremia ⁻ suppuration ⁻ necrotizing bacterial pneumonia ⁻ pulmonary carnification ⁻ hydrolase

VIRAL PNEUMONIA Pneumonia which is an infection by agents intracellular pathogens. It is acute inflammation that is usually restricted to the interstitium. Etiology: ⁻ Caused by mycoplasma pneumoniae and Influenza and parainfluenza viruses. ⁻ Sporadic viral pneumonia (children). ⁻ Respiratory syncytial virus (adults). Pathologic features: ⁻ Expanded alveolar septa ⁻ edema ,hyperemia ⁻ A cellular infiltrate by lymphocytes and plasma cells. ⁻ The alveolar spaces are airfilled ⁻ Infected alveolar epithelial cells ⁻ Necrosis ⁻ variety of inclusion bodies (cytomegalo virus, herpes virus, measles virus). ⁻ Infected alveolar epithelial cells show multinucleated giant cells (respiratory syncytial virus, measles, herpesvirus).

Clinical features: ⁻ Acute onset of fever ⁻ cough unproductive or produced mucoid sputum. ⁻ Dyspnea and illness is usually mild and self-limited. 10 | P a g e

2.THE DEFINITION OF ACUTE INTERSTITIAL PNEUMONIA. ⁻ acute inflammation in the interstitium caused by infection by agents intracellular pathogens. ⁻ Peripheral blood commonly shows neutropenia, lymphocytosis, or no change. ⁻ Caused by mycoplasma pneumoniae and viruses.

3. THE DEFINITION OF COPD. COPD refers to conditions that share a major symptoms – dyspnea – and are accompanied by chronic obstruction of air flow within the lungs. [chronic bronchitis, asthma, emphysema]

4. THE PATHOLOGICAL FEATURES, COMPLICATIONS AND CLINICAL FEATURES OF CHRONIC BRONCHITIS,EMPHYSEMA, BRONCHIAL ASTHMA, BRONCHIECTASIS AND SILICOSIS. CHRONIC BRONCHITIS - Hypersecretion of mucus in large airways - Increase in goblet cells - Fibrous replacement - In the small airways of the lungs [small bronchi & bronchioles] - Reid index (normally 0.4) is increased Complications: ⁻ Progress to chronic obstructive airway disease. ⁻ Lead corpulmonale and heart failure. ⁻ Cause atypical metaplasia and dysplasia of the respiratory epithelium, providing a rich soil for cancerous transformation.

EMPHYSEMA a permanent dilation of the distal air spaces to the terminal bronchiole, usually with destruction of their walls and with termed overinflation. Classification: (1)Alveolar emphysema: containing centriacinar emphysema, panacinar emphysema, periacinar emphysema. (2) Interstitial emphysema. (3) Other types: Paracicatrical emphysema, bullous emphysema, senile emphysema, compensatory emphysema. Pathological features: ⁻ Destruction of lung parenchyma by proteolytic enzymes (proteases, mainly elastase). ⁻ Normally, antiproteolytic substances such as antitypsins in the plasma inactivate these proteolytic enzymes as they are released and thereby protect tissues from damage. ⁻ Alpha-1 antiprotease has antiproteolytic activity. Clinical features: ⁻ patients with COPD are asymptomatic in the early stages of diseases. ⁻ FEV1:FVC ratio is decreased. ⁻ Symptomatic phase, COPD present with a spectrum of symptoms. ⁻ Type A: Patients present with chronic cough either dry or productive of mucoid sputum-progressive dyspnea, and wheezing.The patients successfully maintain oxygenation of the blood by hyperventilation. Type B: Patients have marked chronic obstructive bronchitis and can not hyperventilate. ⁻ There is decreased oxygenation of blood and increased arterial carbon dioxide content. 11 | P a g e

BRONCHIAL ASTHMA ⁻ Bronchial asthma is increased responsiveness of the tracheobronchial tree to a variety of stimuli. ⁻ Exposure to these stimuli leads to bronchiolar smooth muscle contraction. ⁻ The cause of the increased responsiveness of the air passages is unknown but is believed to be related to bronchial inflammation. ⁻ Bronchospasm causes obstruction to airflow – maximal in expiration - and a high-pitched wheeze. ⁻ Expiration is prolonged because of airflow obstruction. Pathological features: ⁻ Bronchiolar obstruction due to smooth muscle contraction, mucoid plugs, and inflammatory edema is maximal in expiration. ⁻ This results in distal air trapping and alveolar distention. ⁻ Vascular congestion, edema, and infiltration by neutrophils and eosinophils. ⁻ The bronchioles become filled with thick mucous secretions. Clinical features: ⁻ episodic attacks of dyspnea and wheezing, dry cough thick, tenacious, scanty sputum, severe attacks, frequently secondary bacterial infection. ⁻ Allergic asthma occurs in childhood and tends to disappear as the child grows. Intrinsic asthma occurs in older individuals and tends to produce a more chronic disease.

BRONCHIECTASIS: It is abnormal and irreversible dilation of the bronchial tree proximal to the terminal bronchioles - in contrast to emphysema, which involves the bronchial tree distal to the terminal bronchioles. Pathological features: ⁻ a patchy distribution, depending on the extent of bronchial obstruction. ⁻ The lower lobes are the most commonly affected. ⁻ The dilated bronchi and bronchioles may be cylindric, or saccular and fibrosis of the intervening lung parenchyma. ⁻ Diagnostic feature is the finding of large bronchi near the pleura. ⁻ The walls of the distended bronchi show inflammation and fibrosis. ⁻ The mucosa may be ulcerated, and the lumen is commonly filled with pus. Clinical features: ⁻ Cough ⁻ sputum, ⁻ hemoptysis.

Silicosis: ⁻ disease caused by inhalation of crystalline silicon dioxide (silica) dust particles in the range of 1-5 um. ⁻ Silicotic lesions may be found long after exposure has been terminated Pathogenesis: ⁻ Small silica crystals, when inhaled, reach the lung acinus. >5 um mucus layer and wafted upward the ciliary action to be expelled. < 1um remain airborne and are exhaled. ⁻ In the alveoli, the silica crystals are phagocytosed by macrophages. ⁻ Silicic acid is toxic to membranes of the macrophages and cell death. ⁻ Inflammation and fibrosis follow, leading to formation of a nodule compose hyalinized collagen around the crystals. 12 | P a g e

Pathological features: ⁻ Grossly, the silicotic nodule is gray-black hard, and brittle and has concentric rings of hyalinized collagen in cross section. ⁻ Nodules are found mainly along lymphatic pathways, especially around the hilum and in the upper lobes. Clinical features: ⁻ exposed to massive amounts of dust, acute lung disease. ⁻ Chronic pulmonary fibrosis with a mild restrictive ventilatory defect, slowly progressive dyspnea, and pulmonary hypertension (cor pulmonale). Complications: ⁻ progressive massive fibrosis ⁻ incidence of tuberculosis (macrophage function) ⁻ silicosis is also associated with an increased incidence of autoimmune disease.

5. THE ETIOLOGY, PATHOGENESIS AND PATHOLOGICAL FEATURES OF CHRONIC COR PULMONALE. Chronic corpulmonale: is right ventricular hypertrophy because of lung disease or disorder. Increased pulmonary blood pressure, or flow, or both, increased pulmonary vascular resistance, left heart resistance to blood flow may all lead to corpulmonale. ETIOLOGY: Chronic obstructive disease, including chronic bronchitis, emphysema, asthma, bronchiectasis, pneumoconiosis, may lead to corpulmonale. Pulmonary hypertension in which destruction of portions of pulmonary vascular bed, vasoconstrivte effects of hypoxemia, and respiratory acidosis which may lead to the hypertension. PATHOLOGICAL FEATURES:  Right ventricle is thickened with an accompanying increase in the weight of the heart.  The right ventricular wall may reach a thickness of more than 1.5 cm, and the weight of the heart may be increased to 500 or to 700g.  Thickness of right ventricular wall exceeding 0.5 in which normal state it would be 0.2-0.3, under the pulmonary artery valve 2 cm is the diagnostic criterion of chronic corpulmonale in pathology.

6. THE ETIOLOGY, CLASSIFICATION, GROSS TYPES, SPREAD AND CLINICAL FEATURES OF CARCINOMA OF THE LUNG. ETIOLOGY: Due to carcinogens, cigarette smoking, urban pollution, radiation, molecular genetics, and scar cancer. CLASSIFICATION: A. SQUAMOUS CELL CARCINOMA: ⁻ Squamous carcinoma arises from the bronchial epithelium. ⁻ It is characterized by intercellular bridges (desmosomes) between tumor cells, and keratinization of the cytoplasm. ⁻ Squamous carcinoma has a strong male predominance, is strongly associated with cigarette smoking. ⁻ Squamous carcinoma tends to remain localized more than the other types, resulting in large masses in the lung. B. ADENOCARCINOMA: ⁻ Adenocarcinoma of the lung, shows glandular differentiation or secretion of mucin by the tumor cells, showing acinar, papillary, bronchioloalveolar or solid with mucin growth pattern or a mixture of these patterns. 13 | P a g e

â ť

It is associated with cigarette smoking although not as strongly as squamous carcinoma and small cell carcinoma. â ť Several different forms of adenocarcinoma are recognized: (1) adenocarcinom arising centrally in large bronchi. (2) Adenocarcinoma arising in peripheral scars in the lungs (scar carcinoma). (3) bronchioloalveolar carcinoma arising in small bronchioles or alveoli, probably from the surfactant-producing Clara cells or from type II pneumocytes. C. SMALL CELL CARCINOMA: - Small cell carcinoma is composed of small round to oval cells with scant cytoplasm. - Small cell carcinoma is believed to arise from neuroendocrine cells in the bronchial mucosa, small cell carcinoma is highly malignant. - Bloodstream metastasis occurs early in the course of the neoplasm. - They almost always occur in the large bronchi near the hilum of the lung. D. LARGE CELL CARCINOMA: - Carcinomas is composed of large cells that show no squamous or glandular differentiation on light microscopy. - Pleomorphic giant cell carcinoma is a highly malignant variant with numerous multinucleated giant cells. PATHOLOGICAL FEATURES: In gross, Central carcinomas arise in the first-, second-, or third-order bronchi near the hilum of the lung. All histologic types occur, but the majority are squamous or small cell carcinomas. PATHOGENESIS: From its mucosal origin, the neoplasm grows into the bronchial lumen (causing ulceration, bleeding, or obstruction) and infiltrates the bronchial wall and adjacent lung parenchyma. There is extensive invasion of the bronchi wall and lung parenchyma, forming a large mass with areas of necrosis and hemorrhage. GROSS TYPES: (1) Peripheral Lung Carcinoma: -

Peripheral carcinomas arise in relation to small bronchi, bronchioles, or alveoli. Peripheral lung carcinomas tend to be adenocarcinomas and, less commonly, squamous carcinomas, small cell carcinoma rarely occurs in the periphery.

(2) Diffuse type: -

On gross examination, this type appears as a diffuse infiltrate of military nodules indistinguishable from lobar pneumonia or tuberculosis.

(3) Early lung cancer: -

The diameter of the tumor is below 2 cm; tumor confined to the wall of a bronchus or infiltrate to the bronchial wall and the surrounding tissues; no lymph node metastasis present.

(4) Occult lung cancer: -

Both clinical and x-ray examinations are negative, but cytology of sputum smears shows cancer cells, biopsy or surgical materials are certified as in situ carcinoma or early infiltrating carcinoma without lymph node metastasis.

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7. THE DEFINITION OF CONDOLIDATION, ACUTE CONGESTION, RED HEPATIZATION, GRAY HEPATIZATION, BRONCHOPNEUMONIA, INTERSTITIAL PNEUMONIA, EMPHYSEMA, PANACINAR EMPHYSEMA, CENTRIACINAR EMPHYSEMA, PERIACINAR EMPHYSEMA, BULLOUS EMPHYSEMA, BRONCHIECTASIS, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, CHRONIC BRONCHITIS, ASTHMA AND SILICOSIS. - PERIACINAR EMPHYSEMA: - distal acinar emphysema. - It occurs adjacent to areas of fibrosis, scarring, or atelectasis and is usually more severe in the upper half of the lungs. - Since this pattern is accentuated along lobular septa, it is refered to as paraseptal emphysema. - CENTRI-ACINAR EMPHYSEMA: - dilation and destruction the central part of the acinus the respiratory bronchioles. - PANACINAR EMPHYSEMA: - dilation and destruction involve the entire acinus, alveoli and alveolar ducts as well as the respiratory bronchioles. - This type of emphysema is probably associated with a-antitrypsin defeciency. - PULMONARY CONSOLIDATION: - is a region of (normally compressible) lung tissue that has filled with liquid, a condition marked by induration (swelling or hardening of normally soft tissue) of a normally aerated lung. - It is considered a radiologic sign. - PARACICATRICAL EMPHYSEMA: - is known as emphysema associated with lung scarring. - BULLOUS EMPHYSEMA: - bulla is an emphysematous space more than 1 cm in diameter. - Subpleural bullae may appear in any forms of emphysema. - SEVERE ACUTE RESPIRATORY SYNDROME (SARS) - is a contagious and sometimes fatal respiratory illness. - SARS first appeared in China in November 2002. - Within a few months, SARS spread worldwide, carried by unsuspecting travelers. - SARS showed how quickly infection can spread in a highly mobile and interconnected world.

QUESTIONS FROM LAB BOOK 1.What are difference between lobar pneumonia and bronchopneumonia ? 2.Terms  Chronic Obstructive Pulmonary Disease (COPD)  Chronic or pulmonale  Muscularization arterioles  Pulmonary carnification  Hypostatic pneumonia  Aspiration pneumonia  Severe Acute Respiratory Syndrome (SARS)  Silicotic nodule  Acute Respiratory Distress Syndrome (ARDS)  Oat cell carcinoma

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8. DISEASES OF DIGESTIVE SYSTEM

9 LECTURES

EXAM PATTERN :: 1 TERM, 1 LONG QUESTION TO MASTER 1. The types of chronic gastritis. 2. The pathological changes, outcome and complications of peptic ulcer diseases. 3. The predilection site, the naked eye morphology and the common histological type of digestive tract carcinoma (including esophageal carcinoma, gastric carcinoma, colorectal carcinoma) as well as the concept of the early carcinoma. 4. The basic pathological changes, pathological types, and clinical pathological relationship of hepatitis virus. 5. The gross and microscopic features, clinical pathological relationship of cirrhosis (such as portal hypertension and hepatic failure). 6. The types of gross morphology and histology, and diffuse characteristics of primary liver cancer. 7. The term explanations: early gastric carcinoma, leather-bottle stomach, piecemeal necrosis, bridging necrosis, cirrhosis of the liver.

TERMS EXPLANATION REFLUXED ESOPHAGITIS (newly added) It is believed to occur when there is prolonged exposure of the mucosa to refluxed gastric contents. The associated clinical condition is termed gatroesophageal reflux disease (GERD).

BARRET’S ESOPHAGUS Prolonged reflux esophagitis commonly leads to metaplasia of the esophageal epithelium from squamous to glandular.It is defined as presence of glandular mucosa showing intestinal metaplasia.

PEPTIC ULCER DISEASE (newly added) They are ulcers occurring in any part of the gastrointestinal tract exposed to the action of acidic gastric juice. They occur principally in the duodenum and stomach.

EARLY GASTRIC CARCINOMA  Defined as gastric carcinoma restricted to the mucosa and submucosa.  It appears as a small, flat mucosal thickening that may have a minimal polypoid and ulcerative component.

LEATHER – BOTTLE STOMACH / LINITIS PLASTICA Its type of late gastric cancer which appear as diffusely infiltrating lesion that causes thickening and contraction of the stomach wall with relatively little mucosal involvement [linitis plastica]

PIECEMEAL NECROSIS A type of necrosis in viral hepatitis in which liver cells at the interface between Parenchyma and fibrous tissue are destroyed, together with lymphocytic or plasma cell infiltrate.

BRIDGING NECROSIS Sub massive necrosis is the occurrence of liver cell necrosis that extends across lobular boundaries, often bridging portal areas and central veins.

GROUND – GLASS HEPATOCYTES Its a histologic change in which hepatocytes infected with hepatitis B virus show this appearance “groundglass” that contrasts with the coarsely granular cytoplasm of uninfected hepatocytes. 16 | P a g e

OR  In chronic hepatitis B or HBV carrier caused by accumulation of HBsAg in cytoplasm.  Have large, pale, finely granular, pink, cytoplasmic inclusion on HE staining.  Immuno-staining confirms that the endoplasmic Reticulum is ballooned with surface antigen [brown], HBsAg, hepatits B surface antigen.

CIRRHOSIS OF THE LIVER Cirrhosis is a chronic degenerative disease in which normal liver cells is damaged and are replaced by scar tissue. OR Its a pathologic entity characterized by necrosis of liver cells, slowly progressive over a long period and ultimately causing chronic liver failure and death; fibrosis which involves both central veins and portal areas; regenerative nodules; distortion of normal hepatic lobular architecture; diffuse involvement of the whole liver.

REVIEW QUESTIONS 1.Describe the relationship among reflux esophagitis, Barrett’s esophagus and esophageal carcinoma. 2.Describe the sites and pathological changes of esophageal carcinoma 3.Describe the pathological changes of chronic atrophic gastritis. 4.Compare the macroscopic difference between benign and malignant gastric ulcer. 5.Describe complications of chronic peptic ulcer.P227 6.Describe the pathogenesis of chronic peptic ulcers.P224-225 7.Describe grossly the pathological changes of advanced gastric carcinoma 8.Describe the basic pathological changes of viral hepatitis. 9.Describe the pathological changes of chronic hepatitis. 10.What are pathological features of liver cirrhosis? P253 11.Describe the clinical features of liver cirrhosis P253-255 12.Describe the pathological features of hepatocellular carcinoma

1.DESCRIBE THE RELATIONSHIP AMONG REFLUX ESOPHAGITIS, BARRETT’S ESOPHAGUS AND ESOPHAGEAL CARCINOMA. (newly added) o REFLUX ESOPHAGITIS believed to occur when there is prolonged exposure of the mucosa to refluxed gastric contents. Clinically termed as gastroesophageal reflux disease(GERD) o Causing Reddening and superficial erosion, Severely, ulceration and fibrous narrowing BARRETT’S ESOPHAGUS is Metaplasia of the esophageal epithelium from normal squamous to glandular columnar. o Heartburn, dysphagia, noticeable regurgitation of sour-tasting gastric contents o ESOPHAGEAL CARCINOMA o Most primary adenocarcinoma of the lower esophagus arise in Barrett's esophagus. o Esophageal carcinoma can spread to adjacent organs or tissue directly. o Lymph nodes metastases and blood stream metastases can occur ,usually depending on the region of the tumor

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2.DESCRIBE THE SITES AND PATHOLOGICAL CHANGES OF ESOPHAGEAL CARCINOMA (newly added) o Occurs in older people (over 40 years) o more common in males. o The common site is the distal third of the esophagus. The pathological changes of esophageal carcinoma are: o mostly ARISEN IN THE DISTAL THIRD OF ESOPHAGUS and may INVADE THE ADJACENT GASTRIC CARDIA o The EARLY LESIONS: a plaque like thickening of the mucosa o The ADVANCED LESIONS; Macroscopically, ADVANCED ESOPHAGEAL CARCINOMA is divided into following types: (1) polypoid/fungating mass (2) malignant ulcer (3) narrowing  involves the whole esophagus circumference, fibrotic response causes narrowing. (4) medulla (special)

3. DESCRIBE THE PATHOLOGICAL CHANGES OF CHRONIC ATROPHIC GASTRITIS. (newly added) CHRONIC GASTRITIS o Chronic gastritis is defined histologically as an increase in the number of lymphocytes and plasma cells in the gastric mucosa，with/without intestinal metaplasia. o Are of 2 types :: ⁻ Chronic superficial gastritis :: an inflammatory infiltration of lymphocytes and plasma cells. ⁻ Chronic atrophic gastritis CHRONIC ATROPHIC GASTRITIS with gland atrophy, mucosa is more obviously thinned and flattened, reddened as the submucosal vessels become more apparent. Pathological Changes  The mucosa is more obviously thinned and flattened  The submucosal vessels become more apparent. OR -

lymphocyte and plasma cell infiltration glandular atrophy lamina propria fibrosis intestinal metaplasia

4.COMPARE THE MACROSCOPIC DIFFERENCE BETWEEN BENIGN AND MALIGNANT GASTRIC ULCER. BENIGN SIZE :: Diameter SHAPE MARGIN BASE EDGE MUCOSA

< 5 cm Circle Flat, non – elevated Clean, smooth Radiate outward Regenerating epithelium

MALIGNANT > 5 cm Irregular, Utensil bottom Raised, everted Shaggy – necrosis, hemorrhage Radiation is interrupted Malignant epithelial cells

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5.DESCRIBE COMPLICATIONS OF CHRONIC PEPTIC ULCER. - The major site is first part of duodenum and gastric antrum. - The complications of peptic ulcer include hemorrhage, penetration of adjacent organ, perforation, pyloric obstruction and malignancy. 1. HEMORRAGE / BLEEDING  Erosion of blood vessels by ulcer in 30% patients.  If slow, it causes occult blood loss in feces.  If brisk, hematemesis or melena occurs.  Anemia 2. PERFORATION/ PENETRATION  Occurs in about 5 %  Most common in anterior duodenal ulcers.  Responsible for over 70 % of deaths.

PENETRATION  Ulcerative process extend into adjacent organs.  Penetration  Pancreatic substance  Constant Back Pain

3. PYLORIC OBSTRUCTION / STENOSIS  Fibrosis of pyloric canal or first part of duodenum 4. MALIGNANT TRANSFORMATION  About 1 % gastric ulcer.  Duodenal ulcers never.

6.DESCRIBE THE PATHOGENESIS OF CHRONIC PEPTIC ULCERS. 1. HYPERSECRETION OF ACID  Acid is necessary for peptic ulcers to form and ulcers do not occur in achlorhydric state.  Exact casual role played by acid is uncertain.  Patients with  DUODENAL ULCER have increased acid secretion with heightened response to normal stimuli.  GASTRIC ULCERS frequently have normal or low acid population.

2. DECREASED MUCOSAL RESISTANCE TO ACID  Decreased resistance of mucosa to acid is believed to be the primary cause of most GASTRIC ULCERS.  Prostaglandins E2 levels in gastric juice have been shown to be constantly decreased in patients with PEPTIC ULCER.

3. HELICOBACTER PYLORI INFECTION  H. Pylori grows in the surface layer [mucous] which may become altered, decreasing mucosal resistance.

 H. Pylori infection is present in 75 % patients [CHRONIC DUODENAL ULCER]

7.DESCRIBE GROSSLY THE PATHOLOGICAL CHANGES OF ADVANCED GASTRIC CARCINOMA (newly added) o FUNGATING/POLYPOID TYPE :: protruding into the lumen o ULCERATIVE TYPE :: raised, everted edges o DIFFUSELY INFILTRATING TYPE / LEATHER-BOTTLE STOMACH/ LINITIS PLASTICA. :: The diffusely infiltrative lesion that causes thickening and contraction of stomach wall with relatively little mucosal involvement called leather bottle stomach. 19 | P a g e

8.DESCRIBE THE BASIC PATHOLOGICAL CHANGES OF VIRAL HEPATITIS. Although the Pathogenesis of the liver cell damage resulting from viral hepatitis is different, the morphology of liver in a typical case is very similar. a) DAMAGES OF LIVER CELLS :: Alteration 1. Degeneration of liver cells -

Cytoplasmic swelling of liver cells Typically, ballooning degeneration, most common Fatty degeneration Acidophilic degeneration

Apoptosis of individual liver cells

Necrosis of liver cells

The apoptosis is recognizable by the formation of eosinophilic councilman bodies [acidophilic bodies] Focal Necrosis Bridging Necrosis Piecemeal Necrosis Sub massive & Massive (Panacinar) Necrosis

b) INFLAMMATORY CELLS INFILTRATION :: Exudation Infiltration of portal tract by mixed inflammatory cells [Lymphocytes & Plasma cells].

c) PARENCHYMAL REGENERATION & INTERSTITIAL REACTION :: Proliferation -

Hepatocytes regeneration Kupffer’s cell hyperplasia Bile ductules Proliferation

Fibroblast / HSCs proliferations – Fibrosis cirrhosis.

9. WHAT ARE THE TYPE AND MORPHOLOGY OF ALCOHOLIC LIVER DISEASE? (newly added and question replaced) (1) FATTY LIVER/HEPATOCELLULAR STEATOSIS: - Chronic - Macrovacular - Reversible (2) ACUTE ALCOHOLIC HEPATITIS: - focal necrosis with neutrophils - cholestatasis  jaundice - alcoholic hyalin (Mallory body) (3) CHRONIC ALCOHOLIC LIVER DISEASE: - ongoing focal necrosis - centrilobular and sinusoid fibrosis - some regeneration conserving normal architecture - irreversible - may not be progressive (4) ALCOHOLIC CIRRHOSIS: ongoing focal necrosis extensive fibrosis regenerative nodules loss of normal architecture progressive and irreversible

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(question replaced instead old question was DESCRIBE THE PATHOLOGICAL CHANGES OF CHRONIC HEPATITIS.)

Characterized in increasing severity 1. Asymptomatic carrier state with normal liver histology. 2. Minimal chronic hepatitis [chronic persistent hepatitis]. 3. Chronic active hepatitis, characterized by continuing necrosis of liver cells [piecemeal necrosis]. ` NECROSIS

MILD Spotty

MODERATE Piecemeal few bridging

INFLAMMATORY CHANGES FIBROUS TISSUE HYPERPLASIA LOBULAR ARCHITECTURES

+ / - Portal areas

Severe intra – lobular

Portal areas

Fibrous septa

___

Most ( - )

SEVERE  Severe  Large Severe / Portal areas necrosis Large amount of Fibrous septa Destroyed

10.WHAT ARE PATHOLOGICAL FEATURES OF LIVER CIRRHOSIS ? Three processes are central to the pathogenesis of cirrhosis 1. Death of hepatocytes 2. Extracellular matrix deposition 3. Vascular reorganization

GROSSLY     

Early stages: The liver is enlarged. Late stages: The liver becomes smaller. It is much firmer than normal. Diffuse nodularity is the most characteristic feature. Depending on whether the nodules > or < 3 cm, it is classified as macronodular, micronodular, or mixed.

HISTOLOGICALLY  Fibrous septa - Vasculature of liver is greatly distorted.  Parenchymal nodules - Diffuse regenerative nodules - They are composed of hyperplastic / dysplasia liver cells organized into irregular plates.

11.DESCRIBE THE CLINICAL FEATURES OF LIVER CIRRHOSIS CHRONIC LIVER FAILURE  Decreased synthesis of albumin, low serum albumin levels, edema and ascites.  Decreased levels of Prothrombin and of factors VII, IX and X – a bleeding tendency.  Hepatic Encephalopathy :: It is characterized by cerebral dysfunction [hypersomnia, delirium, flapping tremors of hands] leading to convulsion, coma and death.  Hepato-renal syndrome :: Occurrence of acute renal failure  Endocrine changes :: Disordered metabolism of certain hormones, testicular atrophy and small vascular telangiectasia in the skin [spider angiomas]  Fetor hepaticus :: breathe like that of “a freshly opened corpse” due to deficient methionine  Jaundice and liver hand 21 | P a g e

PORTAL HYPERTENSION : Causes :: Presinusoidal: Obstruction of intrahepatic / extrahepatic portal veins. Sinusoidal: Fibrosis and distortion of sinusoids, arterio-venous anastomoses. > Splenomegaly > Portosystemic shunt :: Development of Portosystemic venous anastomoses – bypassing the obstructed portal circulation.

> Ascites

12.DESCRIBE THE PATHOLOGICAL FEATURES OF HEPATOCELLULAR CARCINOMA o Early stage :: - Appear single node and diameter less than 3 cm or less than 2 nodules and total diameters less than 3cm, with clinically asymptom. But serum AFP Positive, no hemorrhage and necrosis in nodules with obvious border. o Present as ::  A large solitary mass  Multiple nodules  A diffusely infiltrative lesion Microscopically, o Variable differentiation  Well – differentiated : cells arranged in cords separated by sinusoids  Less well – differentiated : sheets of anaplastic cells. o Serum AFP assay :: an important diagnostic test. SPREAD and METASTASES o Intrahepatic spread of tumor and vascular invasion common.  Invasion to portal vein branches  Intrahepatic metastasis o Invasion to hepatic vein – lungs, bones, adrenals o Implantation metastases QUESTIONS FROM LAB BOOK 1.Compare the macroscopic features of benign gastric ulcer with malignant gastric ulcer. 2.Name the sites affected and the pathogenesis of peptic ulcer. 3.What are the causes and pathological features of liver cirrhosis? 4.Describe the risk factor associated with chronic gastritis. 5.Summarize the features of the colorectal carcinoma. 6.Describe the correlation of hepatitis, cirrhosis and primary hepatocellular carcinoma. 7.Terms  Cirrhosis of liver  Early gastric carcinoma  Intestinal metaplasia  Pseudopyloric metaplasia  Acidophilic body (Councilman body)  Spotty necrosis  Piecemeal necrosis  Bridging necrosis  Alcoholic hyaline body (Mallory body)  Liver cirrhosis  Pseudo lobule  “Ground glass” hepatocyte

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9. DISEASES OF IMMUNITY TO MASTER 1. The features of systemic lupus erythematosus (SLE), rheumatoid arthritis including clinical presentation, morphology. 2. Vocabulary/Related Terms: Libman-Sachs endocarditis; wire loop lesions; pannus; rheumatoid nodules; hyperacute rejection; acute rejection; chronic rejection

THE FEATURES OF SYSTEMIC LUPUS ERYTHEMATOSUS (SLE), RHEUMATOID ARTHRITIS INCLUDING CLINICAL PRESENTATION, MORPHOLOGY.

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)  It affects young women, is characterized by the formation of autoantibodies to many endogenous antigens (e.g., DNA,RNA, nuclear proteins).  Circulating immune complexes are deposited in many tissues, causing organ-specific lesions.  CLINICAL MANIFESTATION - Circulating immune complexes are deposited in many tissues, causing organ-specific lesions. - Skin :: - Rashes :: butterfly rash, rash in chest [ rashes ← skin inflammation ← Ag + Ab + C ] - Digital gangrene :: [←vasculitis ← Ag+Ab+C Thrombosis ] - Skin ulceration :: [skin ulceration ← vasculitis ← Ag+Ab+C ] - Small vessels vasculitis - Arterioles fibrinoid necrosis - Thrombosis - Vascular intimal fibrosis (onion skin appearance) - Kidney - Most common death in SLE -

Proteinuria, microscopic hematuria, nephrotic syndrome, acute nephritic syndrome, renal

failure and low serum complement levels during the active phase - Glomerulonephritis  Immune complex deposition Heart - Pericarditis - Myocarditis - Libman-Sachs endocarditis Joints - Joint inflammation (arthritis) - Pain (arthralgia) Nervous System - Vasculitis and Hyperplasia of the lymphoid system Other immune phenomena :: Bleeding tendency, Thrombocytopenia, Hemolytic anemia, Neutropenia

RHEUMATOID ARTHRITIS  CLINICAL MANIFESTATION - Involved joints are swollen (warm and tender, spindled appearance ), painful and stiff (heavy in the morning , light during the night). - Joint deformity occurs early in severe cases. Restriction of movement may cause rapid disuse atrophy of muscles around the joint. - Many patients have systemic symptoms such as low-grade fever, weakness and malaise． 23 | P a g e

Unknown cause for a progressive and potentially deforming arthritis, more common in females, highest age incidence: 25~ 55 years, less common in tropical countries. Articular manifestations: small joints of the hands and feet---the proximal interphalangeal joints, larger joints –less common. Synovial membrane swollen, congested，and thickened → proliferation of granulation tissue → pannus formation → articular cartilage，subchondral bone，and periarticular ligaments and tendons destroied → joint fibrosis.

Extra-articular manifestations: Subcutaneous rheumatoid nodules --granulomas. Microscopy: an area of fibrinoid necrosis of collagen surrounded by palisading histiocytes．

VOCABULARY/ RELATED TERMS: LIBMAN-SACHS ENDOCARDITIS; WIRE LOOP LESIONS; PANNUS; RHEUMATOID NODULES; HYPERACUTE REJECTION; ACUTE REJECTION; CHRONIC REJECTION. LIBMAN-SACHS ENDOCARDITIS  Its a form of nonbacterial endocarditis that is seen in association with systemic lupus erythematosus.  It is one of the most common heart-related manifestations of lupus (the most common being inflammation of the fibrous sac surrounding the heart).

WIRE LOOP LESIONS In the Glomerulus, extensive, subendothelial immune complexes create a circumferential thickening of the capillary wall, resembling rigid “wire loops”

PANNUS In rheumatoid arthritis, Pannus is an abnormal layer of fibrovascular tissue or granulation tissue over a joint surface.

RHEUMATOID NODULES  It is a local swelling or tissue lump, usually rather firm to touch, like an unripe fruit, which occurs almost exclusively in association with rheumatoid arthritis.  Very rarely rheumatoid nodules occur as rheumatoid nodulosis in the absence of arthritis. HYPERACUTE REJECTION It occurs within minutes or hours and results from the attachment of preexisting antibodies to the endothelial cells of the graft, leading to endotheliosis and thrombosis of major vessels. ACUTE REJECTION It occurs days, months, or years after transplantation and is mediated either by antibodies or lymphocytes. The humoral (antibody) response is usually characterized by obliterative vasculitis. CHRONIC REJECTION It usually occurs after several bouts of acute rejection, from which it differs only in the degree of vascular obliteration,

TERMS BEHIND PPT 24 | P a g e

Allergen An agent that causes IgE-mediated hypersensitivity reactions, e.g. pollen, house dust mite. Allergy Common term for a type I hypersensitivity reaction. Alternative pathway The complement cascade pathway, which is triggered by a variety of factors such as tissue damage and starts with C3. Anaphylaxis The antigen-specific immune reaction mediated by IgE which results in systemic vasodilatation and constriction of smooth muscle (including those of the bronchus), leading to shock and sometimes death. Antibody A molecule produced by B cells in response to antigen with which it can specifically bind. Antigen A molecule which reacts with preformed antibody on B cells and T cell receptors. Antigen-Presenting cells (APC) These can process and present antigen to lymphocytes. Examples are the dendritic reticulum cells in follicle centres, and the Langerhans cells of the skin. CD markers Cluster differentiation markers are molecules on leucocytes and platelets that can be recognised with monoclonal antibodies and may be used to differentiate different cell populations. Complement C1-C9 are the serum protein components of the complement cascade which are responsible for mediating inflammatory reactions, opsonisation of particles and cell lysis. The cascade can be activated by the immune system (classical pathway) or by tissue damage (alternate pathway). Cytokines A family of messenger proteins which stimulates the maturation or activation of a variety of cells including lymphocytes and macrophages. Originally known as lymphokines, when it was thought that they were only secreted by lymphocytes, cytokines have a wide variety of different physiological and pathological effects, including the maturation of haemopoietic stem cells. GRAFT VERSUS HOST DISEASE It typically occurs following bone marrow transplants. T lymphocytes transplanted with other hematopoietic cells attack the host cells or secrete cytokines that adversely affect the transplant recipient. 1. Dermatologic manifestations: They include desquamative dermatitis in the acute phase and sclerosis in the late phase. 2. Hepatic findings: Bile duct destruction leads to cholestatic jaundice. 3. Hematologic findings: Bone marrow involvement leads to suppression of normal hematopoiesis. 4. Gastrointestinal findings: Epithelial cell necrosis results in malabsorption and bloody diarrhea.

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10. DISEASES OF THE URINARY SYSTEM QUESTIONS FROM PPT 1. TERMS - Acute nephritic syndrome - Nephrotic syndrome - Circulating immune complexes - Immune complexes in situ - IgA nephropathy - Crescent - End-stage kidney 2. Chronic glomerulonephritis morphology and clinical menifestations 3. Acute diffuse profiferative GN morphology and clinical menifestations 4. Membranous nephropathy morphology and clinical menifestations

1. TERMS - Acute nephritic syndrome  acute onset  hematuria  mild to moderate proteinuria  azotemia  edema  hypertension

- Nephrotic syndrome  heavy proteinuria (more than 3.5 g of protein /day),  hypoalbuminemia, severe edema, hyperlipidemia, lipiduria  (hypoalbuminemia→colloid osmotic pressure↓ → edema)

- Circulating immune complexes  Ag is not glomeruli origin  Ag-Ab complex are formed in blood circulation and is TRAPPED in glomeruli. - Immune complexes in situ  The Antigen is fixed in glomeruli  Ag-Ab complex are FORMED in glomerulus - IgA nephropathy  Also known as BERGER DISEASE  Deposition of IgA in mesangium  Seen in children and young adults  Most common manifestation is Hematuria  Most common glomerular disease worldwide. 26 | P a g e

- Crescent Constitution  proliferation of parietal cells  migration of monocytes and Tcell  contains fibrin strands Harm  obliterate Bowman's space  compress the glomeruli Cellularity ~ →fibroid ~→ scarring - End-stage kidney As the damage of cell structure progress, it may become difficult as certain whether the primary lesion was glomerular, vascular or interstitial. Such markedly damaged kidneys are called End-stage Kidney. 2. Chronic glomerulonephritis morphology and clinical manifestations MORPHOLOGY GROSS  Kidney contracted  Their surface red-brown  Granular MICROSCOPY ⁻ scarring and hyalinization of the glomeruli ⁻ interstitial fibrosis ⁻ atrophy of tubules in the cortex ⁻ lymphocytes (rarely, plasma cell) infiltration in the interstitial tissue ⁻ small and medium-sized arteries sclerosis ⁻ a part of nephron hypertrophy ⁻ ‘end – stage kidneys’

CLINICAL MANIFESTATION ⁻ developing insidiously ⁻ discovered only late in its course ⁻ usually first suspected with the discovery of proteinuria, hypertension, or azotemia on routine medical examination ⁻ In some patients, nephritic or the nephrotic syndrome ⁻ the nephrotic syndrome less common with more advanced disease 27 | P a g e

⁻ Hypertension is very common ⁻ microscopic hematuria usually present, grossly bloody urine rare ⁻ Without treatment, the prognosis is poor

3. Acute diffuse profiferative GN morphology and clinical manifestations MORPHOLOGY GROSS  Enlarge  Red  Scattered petechial hemorrhages LIGHT MICROSCOPE ⁻ Glomeruli: volume ↑, cells↑, lack of blood ⁻ Proliferation: endothelial and mesangial cells ⁻ Infiltration: neutrophil and monocyte ⁻ Thrombi: capillary lumina* [sometimes] ⁻ Necrosis: capillary walls* [sometimes] ⁻ Mesenchyme: hyperemia ELECTRON MICROSCOPE immune complexes arrayed a subendothelial, intramembranous, or often subepithelial "humps" IMMUNOFLURESCENCE IgG and complement within the deposits

CLINICAL MANIFESTATION  ONSET : ABRUPT malaise, a slight fever, nausea  ACUTE NEPHRITIC SYNDROME oliguria,azotemia, hypertension, mild to moderate proteinuria, edma, gross hematuria (smoky brown)  SERUM ANTISTREPTOLYSIN O TITERS are elevated in poststreptococcal cases.

4. Membranous nephropathy morphology and clinical manifestations MORPHOLOGY  GROSS APPEAR  LIGHT MICROSCOPY  diffuse thickening of the GBM

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 ELECTRON MICROSCOPY  subepithelial deposits  spike like protrusions of GBM matrix  the podocytes lose their foot  IMMUNOFLUORESCENCE MICROSCOPY  deposition of immunoglobulins and complement

CLINICAL MANIFESTATION  nephrotic syndrome  nonselective proteinuria  poor response to corticosteroid  about 40%: renal failure after 2 to 20 years  10% to 30%: partial or complete remission of proteinuria QUESTIONS FROM LAB BOOK

1. Outline the morphological characteristics of acute diffuse proliferative glomerulonephritis and chronic sclerosing glomerulonephritis and analyse the clinical manifestation. 2. Terms ::  Cresent  Nephrotic syndrome  Acute nephritic syndrome

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11. DISEASES OF THE GENITAL SYSTEM AND BREAST QUESTIONS FROM PPT

1. To describe the morphologic features of complete Mole 2. To describe the morphologic features of chronic cervicitis 3. TERMS • Cervical Intraepithelial Neoplasia, Cin • Microinvasive Carcinoma Of The Cervix • Lobular Carcinoma In Situ • Ductal Carcinoma In Situ • Nabothian Cysts

1. To describe the morphologic features of complete Mole In complete moles, all the chromosomal material is derived from sperms. The molar karyotype is 46, XX. In 10%, including Y chromosomes. Early embryonic death, and no fetal parts are seen. GROSS  The uterus is usually enlarged.  The uterine cavity is filled with a mass of grape-like structures - thinwalled, translucent, cystic, and grayish-white.  This represents the hydatidiform mole.  No normal fetal parts are identified. MICROSCOPICALLY  the cysts are composed of hydropic chorionic villi, the interior being filled with an avascular, loose myxoid stroma.  Trophoblastic proliferation produces sheets of cytotrophoblastic and syncytotrophoblastic cells.  Cytologic atypia may be present.

2. To describe the morphologic features of chronic cervicitis (1) The squamocolumnar junction comes to lie below the exocervix. This“exposed” columnar epithelium may appear reddened and moist and has been called cervical“erosion”. This term is misleading however, nothing is really being eroded and the condition is entirely normal. These cervical changes is a natural response to the female hormone. (2) Frequently, overgrowth of the regenerating squamous epithelium blocks the orifices of endocervical glands to produce retention (nabothian) cysts. Fibrous stenosis of gland ducts leading to nabothian cysts, too. (3) Squamous metaplasia of the endocervical epithelium is common. (4) Polyps are common lesions of the endocervical canal, usually occurring at about the time of menopause. Microscopically, endocervical polyps contain hyperplastic endocervical glands and a highly vascular stroma and may show marked chronic inflammation. The surface epithelium of a polyp commonly shows squamous metaplasia. Endocervical polyps are benign. 3. TERMS CERVICAL INTRAEPITHELIAL NEOPLASIA, CIN (also known as cervical dysplasia and cervical interstitial neoplasia): is the potentially premalignant transformation and abnormal growth (dysplasia) of squamous cells on the surface of the cervix. CIN is a precancerous lesion, and is usually curable. MICROINVASIVE CARCINOMA OF THE CERVIX Microinvasive carcinoma of the cervix is defined as cervical carcinoma in which the total depth of invasion is less than 5mm from the basement membrane. LOBULAR CARCINOMA IN SITU a neoplastic proliferation of lobular epithelial cells that fill and distend all the acini of at least one complete 30 | P a g e

lobular unit, obliterating their lumens. Tumor cells consist of small cells that have oval or round nuclei with small nucleoli that do not adhere to one another. Basement membrane is intact. DUCTAL CARCINOMA IN SITU increased proliferation of ductal epithelial cells confined within the BM and subtle to marked cellular atypia. Frequently multifocal, and commonly associated with infiltrating ductal carcinoma. NABOTHIAN CYSTS (or nabothian follicle) is a mucus-filled cyst on the surface of the cervix. They are most often caused when stratified squamous epithelium of the ectocervix (toward the vagina) grows over the simple columnar epithelium of the endocervix (toward the uterus). In other word, frequently, overgrowth of the regenerating squamous epithelium blocks the orifices of endocervical glands to produce retention (nabothian) cysts.

QUESTIONS FROM LAB BOOK 1. What are the spread routes and serious results of cervical carcinoma and carcinoma of breast ? 2. How to differentiate the hydratid-form mole, invasive mole and choriocarcinoma ? 3. Terms ::  Cervical intraepithelial neoplasia (CIN)  Adenoacanthoma A malignant neoplasm consisting chiefly of glandular epithelium (adenocarcinoma), usually well differentiated, with foci of squamous (or epidermoid) neoplastic cells.

    

Adenosquamous carcinoma Prostatic-specific antigen (PSA) Intraductal carcinoma in situ Comedocarcinoma Lobular carcinoma in situ

 Paget disease Eczematous changes in nipples and surrounding skin Presence of large carcinoma cells with abundant cytoplasm in epidermis Carcinoma cell with mucin plus

EXTRAS Invasive carcinoma: is defined as carcinoma infiltrating to a depth of greater than 5 mm from the basement membrane. It occurs most frequently in the age group from 30 to 50 years.

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12. DISEASES OF THE ENDOCRINE SYSTEM EXAM PATTERN :: 2 TERMS, 1 SHORT (from respiratory/endocrine) TO MASTER

1. The main endocrine organs. 2. The normal structure and function of thyroid gland. 3. The definition, etiology, pathological features and the clinical features of diffuse nontoxic and multinodular goiter, excessive secretion of thyroid hormone. 4. The pathological changes and prognosis of the thyroid follicular adenoma and thyroid carcinoma. 5. The definition and classification of diabetes mellitus.

THE MAIN ENDOCRINE ORGANS > Pituitary > Thyroid > Parathyroid > Adrenal glands > Pancreatic islet

THE NORMAL STRUCTURE AND FUNCTION OF THYROID GLAND  The thyroid is firm, reddish-brown, and smooth.  It is surrounded by a fibrous capsule that blends with the deep cervical fascia  HISTOLOGICALLY, 1. closely packed follicles cuboidal epithelial cells colloid-- thyroglobulin 2. a rich vascular supply 3. little intervening stored Dispersed between the thyroid follicles are the parafollicular or C cells, which secrete calcitonin. THE DEFINITION, ETIOLOGY, PATHOLOGICAL FEATURES AND THE CLINICAL FEATURES OF DIFFUSE NON

TOXIC AND MULTI-NODULAR GOITER, EXCESSIVE SECRETION OF THYROID HORMONE. DIFFUSE NON-TOXIC & MULTI-NODULAR GOITER DEFINITION  represent the culmination of mild deficiency of thyroid hormone production followed by compensatory thyroid hyperplasia  hyperplasia and hypertrophy of the gland corrects the hormone deficiency and maintains the euthyroid  thyroid enlargement  serum TSH levels are increased  deficiency of organic iodine in the cells resulting from impaired hormone synthesis  Note: goiter means enlargement of the thyroid gland due to any cause

ETIOLOGY  The basic cause of diffuse nontoxic and multinodular goiter is failure of normal thyroid hormone synthesis  A. Endemic Goiter the result of chronic dietary deficiency of iodine mainly in inland mountainous regions of the world such as the Alps, Andes and Africa A. Endemic Goiter  up to 10% thyroid enlargement, sometimes massive 32 | P a g e

 not common in coastal communities because of the high iodine content of seawater and seafood  endemic goiter is more common in women because of increased iodine requirements in pregnancy and lactation  The incidence decreased - iodization of common table salt was instituted  due to increased physiologic demand for thyroxine at puberty or during pregnancy ( also called physiologic goiter) B. Sporadic Goiter  less commonly, sporadic goiter may result from mild deficiency of enzymes involved in thyroid hormone synthesis  dietary factors that block thyroid hormone synthesis. They are found in plants such as cabbage and cassava and cauliflower and have been identified as a cause of goiter  In most cases, however, the cause of sporadic goiter is not apparent. PATHOLOGICAL FEATURES  TSH-induced hypertrophy and hyperplasia of thyroid follicular cells results  initially in diffuse, symmetric enlargement of the gland (diffuse goiter)  The follicles are lined by crowded columnar cells, which may pile up and form projections similar to those seen in Graves disease  If dietary iodine subsequently increases, or if the demands for thyroid hormone decrease, the stimulated follicular epithelium involutes to form an enlarged, colloid-rich gland (colloid goiter)  cut surface of the thyroid in such cases is usually brown, somewhat glassy, and translucent  Microscopically, the follicular epithelium may be hyperplastic in the early stages of disease or flattened and cuboidal during periods of involution  recurrent episodes of hyperplasia and involution combine to produce a more irregular enlargement of the thyroid, termed multinodular goiter  Virtually all long-standing simple goiters convert into multinodular goiters. They may be nontoxic or may induce thyrotoxicosis (toxic multinodular goiter)  multinodular goiters are multi-lobulated, asymmetrically enlarged glands, which may reach massive size  On the cut surface, irregular nodules containing variable amounts of brown, gelatinous colloid are present  Regressive changes are quite common, particularly in older lesions, and include areas of fibrosis, hemorrhage, calcification, and cystic change  Microscope, includes colloid-rich follicles lined by flattened, inactive epithelium and areas of follicular epithelial hypertrophy and hyperplasia, accompanied by the regressive changes noted above CLINICAL MANIFESTATION  Individual with congenital thyroid tissue in the mediastinum may present with a mediastinum mass (retrosternal goiter)  Abnormal thyroid hormone production may rarely occur in multinodular goiter  Hyperthyroidism is commoner than hypothyroidism and is due to the development of autonomous hyperplastic nodules in the gland (toxic nodular goiter). The risk of development of carcinoma in a multinodular goiter is small. THE PATHOLOGICAL CHANGES AND PROGNOSIS OF THE THYROID FOLLICULAR ADENOMA AND THYROID

CARCINOMA.

THE DEFINITION AND CLASSIFICATION OF DIABETES MELLITUS ⁻ Diabetes mellitus is a chronic disease characterized by relative or absolute deficiency of insulin, resulting in glucose intolerance. It occurs in 4-5 million persons in the Unite Sates (approximately 2% of the population).

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⁻ The pathologic changes in the pancreatic islets in diabetes mellitus are variable from one patient to another and are not specific for diabetes. In type I diabetes, there is frequently a lymphocytic infiltration of the islets in the early phase, followed by a progressive loss of B cells. ⁻ The changes in type II diabetes are often minimal in the early stages. In advanced disease, there may be fibrosis and amyloid deposition in the islets; in diabetes, the amyloid appears to consist in part of precipitated insulin. ⁻ CLASSIFICATION ⁻ Type I diabetes ⁻ Type II diabetes ⁻ Other specific type of diabetes eg::Disease of exocrine pancreas, genetically, endocrinopathies.

QUESTIONS FROM LAB BOOK 1.

To understand the pathologic changes of nodular goiter and toxic nodular.

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3 LECTURES

13. DISEASES OF NERVOUS SYSTEM TO MASTER 1. The types of infective meningitis and corresponding etiology, infectious routes, morphology of each type. 2. The types, etiology, infectious routes, and pathologic characteristics of cerebral abscess, viral encephalitis (including Japanese B encephalitis) and spongy encephalitis. 3. The terms: soften focus, perivascular cuffing, microglial nodules, neurophagia.

1. THE TYPES OF INFECTIVE MENINGITIS AND CORRESPONDING ETIOLOGY, INFECTIOUS ROUTES, MORPHOLOGY OF EACH TYPE. MENINGITIS 1. Pachymeningitis – dura primarily 2. Leptomeningitis – Pia-arachnoid INFECTIOUS ROUTES  Hematogenous spread  Direct implantation by trauma or NS congenital malformation  Peripheral Nerves AFFECTED TISSUE  Leptomeningitis & Subarachnoid space CLASSIFICATION  Acute purulent meningitis – Bacteria  Acute Lymphocytic meningitis – Viruses  Chronic Meningitis – Numerous different micro organisms

ACUTE LEPTOMENINGITIS SITES :: Piamater and arachinoid ETIOLOGY :: Infectious agents, chemical substances CLASSIFICATION ::  Acute Bacteria meningitis  Acute Viral meningitis  Tuberculous meningitis  Other causes ACUTE BACTERIA MENINGITITS Susceptible group : < 5 years (70%) ETIOLOGY :: - Neonate : E.coli & Streptococcus agalactiae - 1 – 5 years : Haemophilus influenza - 5 – 40 years : Neisseria meningitides - > 40 years : Listeria monocytogenes and G - Bacilli

35 | P a g e

ACUTE VIRAL MENINGITIS Susceptible group : < 30 years (90%) ; Mild, benign disease ETIOLOGY :: - Enterovirus - Mumps Virus - HIV seroconversion - LCM virus [Lymphocytic choriomeningitis]

TUBERCULOSIS MENINGITIS  Chronic  Early stages : exudation  Other causes :: - Fungi - Amebas PATHOLOGY :: - NE :: congested, opaque exudate - LM :: hyperemia, fibrin formation TYPES

BACTERIAL

VIRUS

CHRONIC

Exudate

PMN, Fibrin

LC, MC Plasma cells

Brain substance

Unaffected

Inflammed

Reactive

chronic

inflammation Courses

Severe

Mild, Self-limited

Insidious onset, slow progression

CHRONIC MENINGITIS Etiology :: facultative intracellular organisms, mycobacteria, fungi, Treponema pallidum Pathology :: Marked fibrous thickening  TB : chronic caseous granulomateous inflammation  Syphilis : obstructive vasculitis, Plasma cells, LC

2. THE TYPES, ETIOLOGY, INFECTIOUS ROUTES, AND PATHOLOGIC CHARACTERISTICS OF CEREBRAL ABSCESS, VIRAL ENCEPHALITIS (INCLUDING JAPANESE B ENCEPHALITIS) AND SPONGY ENCEPHALITIS.

THE TERMS: SOFTEN FOCUS, PERIVASCULAR CUFFING, MICROGLIAL NODULES, NEUROPHAGIA. SOFTEN FOCUS Soften foci = Liquefaction necrosis

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Well circumscribed Pale stained Incomplete necrosis PERIVASCULAR CUFFING Perivascular lymphocytic infiltration is perivascular cuffing consists of mononuclear cells including lymphocytes and macrophages. MICROGLIAL NODULES Microglial nodules are usually present are sometimes associated with phagocytosis of neurons by microglia and macrophages. NEUROPHAGIA

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8 LECTURES

14. INFECTIOUS DISEASES EXAM PATTERN :: 2 TERMS, 1 LONG QUESTION TO MASTER 1. Basic and advance pathologic changes, pathomorphology of primary and secondary pulmonary tuberculosis. 2. The difference between primary and secondary pulmonary tuberculosis in terms of age of hosts, infective pathway, localization of the lesion, gross and microscopic changes, radiography and sequelae. 3. The main pathological changes and natural history of secondary pulmonary tuberculosis related to pathological types. 4. The main pathological changes and the commonest tissues involved in extrapulmonary tuberculosis (intestine, kidney, meninges, bone, lymph node). 5. The terms: Caseous necrosis, Epithelioid cell, Langhan’s giant cell, Granuloma, cold abscess, Ghon’s complex (primary complex), Secondary tuberculosis, Tuberculoma. 6. The pathologic characteristics including tissues commonly invaded and main morphologic changes, main infectious routes and susceptible herd of typhoid fever, bacillary dysentery, and leprosy. 7. The types/stages and corresponding pathological changes of typhoid fever, bacillary dysentery, and leprosy. 8. The terms: typhoid cell, typhoid granuloma, pseudomembrane, clear zone, erythema nodosum leprosum, and Lucio’s phenomenon. 9. The pathologic characteristics including tissues commonly invaded and main morphologic changes, main infectious routes and susceptible herd of gonnorhea, condyloma acuminate, syphilis, and AIDS. 10. The difference between gumma and tubercle. 11. The stages of syphilis and main morphologic changes respectively. 12. The effects of HIV infection on immune system, opportunistic infection and malignant neoplasms.

13. The terms: Condyloma acuminate, Koilocytes, Gumma, AIDS, and Kaposi's sarcoma.

1. BASIC AND ADVANCE PATHOLOGIC CHANGES, PATHO-MORPHOLOGY OF PRIMARY AND SECONDARY PULMONARY TUBERCULOSIS. 1. BASIC PATHOLOGIC CHANGES  Tubercle [Tuberculous granuloma]  Caseous necrosis  Exudation – Edema + Hyperemia + PMN + Bacteria  Proliferation – Tubercle + Fever bacteria  Alteration – caseous necrosis + fever bacteria TUBERCLE  Hard  Military  Coarsely granular & dotted lesions

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 Caseous necroisis  Epitheloid cells  Langhan’s cells  Lymphocytes  Fibrosis TUBERCLE – Epithelioid cell  Plentiful  Eosinophilic cytoplasm  Oval vesicular nucleus LONGHAN’S GAINT CELL  Plentiful pink cytoplasm  Multi-nuclei  Marginal ring - arranged CASEOUS NECROSIS  NE :: Thick, pasty, homogeneous, pale yellow-white substance  LM :: eosinophilic substance, homogeneous, lipid-rich, substance less 2. ADVANCE CHANGES IN DEVELOPMENT HEALING  Absorption & Resolution  Fibrious & Calcification DEPRAVATION  Infiltration & Progression  Dissolution & Dissemination BACKGROUND  Large number of organisms  Host Resistance Low LESIONS  Lungs  Meninges  Kidney  Bone marrow  Liver TYPES  Acute systemic military TB  Subacute military TB  Chronic TB ACUTE SYSTEMIC MILITARY TB ::  Pulmonary vein – all of the body  Pulmonary artery/ Lymphatic vessel – Lungs  Studded with white tubercles (≥ 1mm, equal size)  Adult – extra pulmonary origin  Child – muscle tissue exempt SUBACUTE SYSTEMIC MILITARY TB ::  Compared to acute systemic military TB  Military nodule – bigger & fever CHRONIC AND RECURRENT MILARY TB :: 39 | P a g e

 Heavy lungs & Fibrotic pleurae  Cut surface :: coalesced – nodules (central coseation  cavitation)

2. THE DIFFERENCE BETWEEN PRIMARY AND SECONDARY PULMONARY TUBERCULOSIS IN TERMS OF AGE OF HOSTS, INFECTIVE PATHWAY, LOCALIZATION OF THE LESION, GROSS AND MICROSCOPIC CHANGES, RADIOGRAPHY AND SEQUELAE. Types of Pulmonary TB :  1st infection type : childhood type = primary TB  2nd infection type : Adult TB = secondary TB PRIMARY PULMONARY TB :  Primary complex o Central zone of caseous necrosis o Epitheloid histiocytes o Occasional Langhan’s gaint cell o Lymphocytes  Inflammatory Lymphatic vessels  Enlarged regional Lymph nodes

SECONDARY PULMONARY TB  Localized, extensive caseous necrosis  Lung apex

Small epithelioid cell granuloma

Large solid mass of fibrocaseous granuloma (Tuberculoma)

Infective sputum

Spread

Cavitation

Cavitary Fibrocaseous TB

PRIMARY

SECONDARY

SUSCEPTIBLE HERDS

Children

adults

INFECTION

First

second

ORIGINAL FOCUS

basal segment of upper lobes or apical

apex

segment of lower lobes

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IMMUNITY TO BACILLI

→+

PATHOLOGICAL CHANGES

primary complex

new and old lesions, limited

CONSEQUENCE

short, self limited

long, require treatment

SPREAD

lymphatic or blood vessels

bronchi

3. THE MAIN PATHOLOGICAL CHANGES AND NATURAL HISTORY OF SECONDARY PULMONARY TUBERCULOSIS RELATED TO PATHOLOGICAL TYPES. PATHOLOGY :: (given above) NATURAL HISTORY OF ADULT TYPE PULMONARY TB :  Healing  Softening & Cavitaion  Spread

PATHOLOGICAL TYPES::  Focal Pulmonary TB  Infiltrating Pulmonary TB  Chronic fibrotic cavitary TB  Caseous pneumonia  Tuberculoma  Tuberculous pleuritic

4. THE MAIN PATHOLOGICAL CHANGES AND THE COMMONEST TISSUES INVOLVED IN EXTRAPULMONARY TUBERCULOSIS (INTESTINE, KIDNEY, MENINGES, BONE, LYMPH NODE). INTESTINAL TB : Pathological sites : Cecum & Ileum, appendix, colon, Rectum, duodenum

Pathological features : Circumferential ulcers, long axis of ulcers intestines. TUBERCULOUS MENINGITIS : Insidious Prodrome : anorexia/ malaise/ vomit, 2 – 3 weeks  signs of meningeal irritation. RENAL TB : Primary Pulmonary TB  Hematogenous dissemination  Caseous granulomas at corticomedullary region  pelvicaliceal system  discharge of caseous material in urine  Chronic inflammatory o Low grade fever 41 | P a g e

o Numerous neutrophils  Urinary Symptoms o Weight loss o Frequency, mild Lumbar pain o Hematuria TUBERCULOUS BONE : Site :: Thoraic & Lumbar vertebras, Bones of hips, Knee, angle, elbow, wrist Feature :: Caseous granulomas Cold abscess :: Liquified caseous of muscle redness / heat φ LYMPH NODE TB : Pathologic Site :: Pulmonary hilar mode with primary complex, Cervical nodes NE : enlarge, mat together/ cheesy material LM : numerous granulomas 5. THE TERMS: CASEOUS NECROSIS, EPITHELIOID CELL, LANGHAN’S GIANT CELL, GRANULOMA, COLD ABSCESS, GHON’S COMPLEX (PRIMARY COMPLEX), SECONDARY TUBERCULOSIS, TUBERCULOMA. CASEOUS NECROSIS NE : thick, pasty, homogenous, pale yellow-white substance LM : Eosinophilic substance, homogeneous, lipid – rich, structure less [no interstitial fibrous tissue] EPITHELOID CELLS Activated macrophages resembling epithelial cells.  Plentiful, eosinophilic cytoplasm  Oval vesicular nucleus LANGHAN’S GAINT CELL  Plentiful pink cytoplasm, multi – nuclei  Marginal ring – arranged

GRANULOMA Collection of immune cells known as granulocytes found in an inflammation. COLD ABSCESS 42 | P a g e

Liquefied caseous of muscles. Redness / heat φ

GHON’S COMPLEX (PRIMARY COMPLEX)  Basal segment of upper lobe / apical segment of lower lobe, close to pleura  Parenchymal infection  Epithelioid – cell granulomatous inflammation SECONDARY TUBERCULOSIS  Reinfection bacilli – large number from sputum  Reactivation, Breakdown of immunity, Tuberculum – Positive individuals, sub – apical region of upper lobe. TUBERCULOMA  Nodular conglomerate area of caseous necrosis  Well formed fibrous capsule  Cut surface – uniform/ lamellate, dry, caseous 6. THE PATHOLOGIC CHARACTERISTICS INCLUDING TISSUES COMMONLY INVADED AND MAIN MORPHOLOGIC CHANGES, MAIN INFECTIOUS ROUTES AND SUSCEPTIBLE HERD OF TYPHOID FEVER, BACILLARY DYSENTERY, AND LEPROSY. TYPHOID FEVER Sides : Lymphoid tissue of intestine : ileum, cecum, jejunum, appendix, colon Source : Contaminated food, water Fecal oral transmission from patients & carriers. Salmonella typhi  small intestine  regional lymph node. Bacteremic phase

Bacteremia

Bacilli multiply

Intestinal phase

Bacilli re-enter the intestine lumen by bile Bacilli re-infect Lymphoid tissue Acute inflammation, necrosis, ulceration

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BACILLARY DYSENTERY Endotoxin (LPS) – all Fecal oral transmission Natural habitat : Primate gut, Rectum, Sigmoid flexure Bacterial endotoxin Deeper cells lining the intestinal crypts Small abscesses in the mucosal epithelium of colon Pathology : Pseudomembrane and ulceration LEPROSY Sites – skin and PNS – cooler parts Chronic infectious granulomatous disease TUBERCULOUS

LEPTOMATOUS

Cellular immunity

High

Low

Lesions Bacteremia

Small

Widespread common

Similar to

Involved tissue

Rare Peripheral

Skin, eye, upper

Leptomateous type

nerves

respiratory tract

with more bacteria

Palpable Thickening,

Extensive destruction

Symptoms

INTERMEDIATE

nerve palsies Therapy

good

Bad

7. THE TYPES/STAGES AND CORRESPONDING PATHOLOGICAL CHANGES OF TYPHOID FEVER, BACILLARY DYSENTERY, AND LEPROSY. TYPHOID FEVER :: Can be classified into 4 classic stages. 1. Stage of hyperplasia of Payer’s patches 2. Necrotic stage 3. Ulcerative stage 4. Healing stage 8. THE TERMS: TYPHOID CELL, TYPHOID GRANULOMA, PSEUDOMEMBRANE, CLEAR ZONE, ERYTHEMA NODOSUM LEPROSUM, AND LUCIO’S PHENOMENON. ********** ERYTHEMA NODOSUM IC :: Induced Subcutaneous Panniculitis NE :: Painful nodules, tender erythema 44 | P a g e

LM :: Mφ (Bacilli +), PMN, Acute vasculitis LUCIO’S PHENOMENON III hypersentivity – induce flare-up vasculitis Small to medium vessels – lumen narrowed Vessel walls – Bacilli +, Intimal fibrosis 9. THE PATHOLOGIC CHARACTERISTICS INCLUDING TISSUES COMMONLY INVADED AND MAIN MORPHOLOGIC CHANGES, MAIN INFECTIOUS ROUTES AND SUSCEPTIBLE HERD OF GONNORHEA, CONDYLOMA ACUMINATE, SYPHILIS, AND AIDS. GONORRHEA ************* CONDYLOMA ACUMINATE ************* SYPHILIS  Susceptible Herds :: Heterosexual, Homosexual males  Transmission :: Sexual contact & Blood & Placenta GUMMA (Syphiloma) - NE:Irregular, firm, large mass with coagulative necrosis, rubbery (resilient) connective tissue. - LM: Localized destructive granuloma Center :: gummatous (rubbery) necrosis Around :: Epithelioid, Lymphocytes, Plasma cells, Pump fibrosis SMALL BLOOD VESSEL DISEASE - LM: Proliferative endo-arteritis & Periarteritis, Periadventitial cuffing by LC and Plasma cells endothelial cells – swell and Proliferate AIDS 10. THE DIFFERENCE BETWEEN GUMMA AND TUBERCLE. Granuloma

GAMMA

TUBERCLE

Coagulative necrosis

Incomplete, elastic fiber + Complete, cheesy rubbery

Blood vessels

Endoarteritis and Periangitis

Epithelioid & Langhan’s cell

Fewer

Common

Lymphocytes

Numerous

Plasma cells

Numerous

Fewer 45 | P a g e

Absorption, Fibrosis

Common

Calcification

Seldom

Common

11. THE STAGES OF SYPHILIS AND MAIN MORPHOLOGIC CHANGES RESPECTIVELY. PRIMARY SYPHILIS ::  Sites :: male – penis , female – vagina  Primary chancre [ hard chancre ] - NE :: Painless, indurated papule, well defined ulcer, “clean” moist base. - LM :: Infiltration with LC, Mφ, Plasma cells.  Draining LN enlarged  Heal spontaneously in 3 – 6 weeks SECONDARY SYPHILIS :: 7 – 8 week after chancre  Generalized skin rash - NE : 1. Maculopaular skin rash orogenital mucous cutaneous, red/copper colour, snail – track ulcers (mouth) 2. Flat papules [condyloma lata] moist cutaneous, mucosutaneous areas, anus/valva/perineum - LM : Perivascular infiltration, LC, Mφ, Plasma cells TERTIARY SYPHILIS  Destructive lesions  Obstructive endarteritis & Periangitis  Gumma  NEURO SYPHILIS - Meningovascular syphilis - Parenchymatous neurosyphilis  Cardiovascular syphilis – aortitis / aneurysm  Latent syphilis 12. THE EFFECTS OF HIV INFECTION ON IMMUNE SYSTEM, OPPORTUNISTIC INFECTION AND MALIGNANT NEOPLASMS.

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13.

THE TERMS: CONDYLOMA ACUMINATE, KOILOCYTES, GUMMA, AIDS, AND KAPOSI'S SARCOMA.

CONDYLOMA ACCUMINATE  Veneral warts / Genital warts  Local warty papillary condylomatous lesions  HPV 6, II KOILOCYTES Squamous cell with perinuclear vacuole, Heterochromic nucleus GUMMA  Syphiloma ⁻ NE: irregular, firm, large mass with coagulative necrosis, rubbery (resilient) connective tissue ⁻ LM: localized destructive granuloma ⁻ Center --- gummatous (rubbery) necrosis ⁻ Around – epithelioid cells, lymphocytes, plasma cells, plump fibrosis OR A gumma is a soft, non-cancerous growth resulting from the tertiary stage of syphilis. It is a form of granuloma. Gummas are most commonly found in the liver (gumma hepatis), but can also be found in brain, heart, skin, bone, testis,KOILOCYTES and other tissues, leading to a variety of potential problems including neurological disorders or heart valve disease. AIDS  Acquired Immuno Deficiency syndrome  Impaired mediated Immunity o CD4+ T cells  Opportunistic infections  Opportunistic malignancies, HIV antibody + KAPOSI’S SARCOMA It is a malignant vascular cancer that affects the skin and many internal organs and presents purple, red or brown lesions. Relate to HHV-8 infection

QUESTIONS FROM LAB BOOK 1. Compare the morphology of typhoid fever with that of bacillary dysentery, tuberculosis, amoebiasis and schitosomiasis of the intestine. 2. What is the difference between suppurative meningitis and epidemic encephalitis B? 3. Terms ::  Neuronophagia 47 | P a g e

ď&#x201A;ˇ Satellitosis ď&#x201A;ˇ Typhoid nodule SUMMARY TUBERCULOSIS Tubercle Bacillus Tuberculous granuloma Lung Primary and Secondary

Tuberculosis: Etiology Pathologic feature Commonest site Types

Primary TB: Contain Primary complex or Ghon complex which is composed of a focal tuberculosis lesion (Ghon focus), inflammatory lymphatic vessels and enlarged regional lymph nodes. Ghon focus consists of epitheloid-cell granulomatous inflammation at the site of parenchymal infection. Secondary TB: contain Type Focal TB (inactive) Infiltrative TB (active,common) chronic fibrocavitive TB (opening) Caseous pneumonia (fatal) Tuberculoma (time bomb) Tuberculosis pleurisy

Feature Lesion at the apex of lung, self-limited, patient is asymptomatic Focus is invasive and fuzzy, appear as cloudy-like shadows Cavity has necrotic, ragged walls, with adherent pale yellow cheesy material Rapidly progressive, caseous hilar node erodes a bronchial wall and perforation of tuberculous cavity is present Nodular conglomerate area of caseous necrosis Contain humectous tuberculous pleuritis and Siccus tuberculous pleuritis

Miliary TB: consequence of primary/secondary TB, location is lungs, meninges, kidneys, bone marrow, liver, etc. Types of extrapulmonary TB: Extrapulmonary TB intestinal tuberculosis Tuberculous peritonitis Tuberculous meningitis Tuberculous kidney Tuberculous fallopian tubes Tuberculous epididymis Tuberculous osteomyetitis Vertebral tuberculosis

Main comparison between typhoid, bacillary dysentery, and leprosy. Disease Etiological factor Main pathological feature

Site of infections

Typhoid Salmonellosis typhi typhoid nodule/proliferation of reticuloendothelial system, systemic, PMN ileum & cecum

Bacillary dysentery Shigella Colitis pseudomembrane & ulceration

rectum, sigmoid flexure

Leprosy mycobacterium leprae Epithelioid cell granulomas Macrophage with many bacilli skin and PNS --- cooler parts of body 48 | P a g e

Transmission

Fecal-oral transmission Fecal-oral transmission from patients & carriers

person to person with low infectivity rates

Types of leprosy:

STDs: Etiological factors: Human pappillomavirus (HPV) ---condyloma acuminatum Human immunodeficiency virus(HIV)---AIDS Neisseria gonorrhoeae---gonorrhea Treponema pallidum---syphilis Features of the Diseases: Gonorrhea CONDYLOMA ACUMINATUM

SYPHILIS---stage I

SYPHILIS---stage II SYPHILIS---stage III

AIDS

Acute suppurative inflammation Urethra and periurethral glands Young adults Males---Glans penis and inner lining of the prepuce or in the terminal urethra Histology Epidermis---pappilomatous hyperplasia Koilocytes---cytoplasmic vacuolation HPV-6, 11 Primary chancre---penis Painless indurated nodule Ulcer with rounded margins Endarteritis---perivascular infiltration of LC and plasma cells Inguinal lymphadenitis Condylomata lata Generalized lymphadenitis Gumma Thoracic aortic aneurysms Central nervous system changes Impaired cell-mediated immunity Opportunistic infections Unusual malignancies---Kaposiâ&#x20AC;&#x2122;s sarcoma HIV---blood, semen, saliva, vaginal , and breast milk

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PREVIOUS YEAR QUESTIONS PATHOLOGY 2012 BATCH (memorized by a senior) TERMS 1. 2. 3. 4. 5. 6.

ASCHOFF BODIES AUTOPHAGY ONCOBETAL ANTIGEN LEATHER BOTTLE STOMACH WARBURG EFFECT GANGRENE

SHORT AND LONG QUESTIONS 1. 2. 3. 4. 5. 6. 7. 8.

PATHOLOGICAL FEATURES OF GASTRIC CARCINOMA. DIFFERENCE BETWEEN BENIGN AND MALIGNANT NEOPLASM. DIFFERENCE BETWEEN NECROSIS AND APOPTOSIS THE ETIOLOGY, MORPHOLOGY, PATHOLOGY, CLINICAL MANIFESTATION OF TYPHOID, DYSENTRY AND LEPROSY. THE NOMENCLATURE OF BENIGN AND MALIGNANT NEOPLASM. EXPLAIN THE FATE OF THROMBOSIS. ETIOLOGY, PATHOLOGICAL FEATURES, COMPLICATIONS, CLINICAL FEATURES OF LOBAR PNEMONIA. THE CLINICAL FEATURES AND THE COMPLICATION OF HYPERTENSION INCLUDING THE HEART, CNS, KIDNEY, BLOOD VESSEL.

2014-2015 (2nd SEM) AND PREVIOUS QUESTIONS TERMS 1.

ATROPHY

   2.

GANGRENE 

   3.

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. normally formed → small parenchyma cells of an organ

Extensive tissue necrosis with putrefaction is complicated to a variable degree by secondary bacterial infection foul-smelling gas brown, green or black discoloration Are classified into Dry, Wet and Gas Gangrene

AUTOPHAGY

Autophagy (autophagocytosis): self-eating, lysosomal digestion of cell's own components.

EDEMA

Condition of excess fluid in the interstitial space 5.

CHRONIC INFLAMMATION

Chronic inflammation is of longer duration (days to years) and is typified by influx of lymphocytes and macrophages with associated vascular proliferation and scarring. 50 | P a g e

WARBURG EFFECT

Cancer cell obtain most of their energy from glucose using glycolytic pathways rather than from the oxidative breakdown of pyruvate in mitochondria. 7.

PRICANCEROUS LESION

A pre-malignant or pre-cancerous lesion is an abnormality in a tissue area which is just a step away from cancer. 8.

COCENTRIC HYPERTROPHY

> Left ventricular hypertrophy and normal size of the chamber. > With long-standing and severe hypertension, left ventricular dilation and failure occurs 9.

ATHEROSCLEROSIS

ATH is a disease of large and medium-size arteries that results in progressive accumulation within the intima of SMCs, lipids and connective tissue. 10. INTERSTIAL PNEUMONIA o acute inflammation in the interstitium caused by infection by agents intracellular pathogens. o Peripheral blood commonly shows neutropenia, lymphocytosis, or no change. o Caused by mycoplasma pneumoniae and viruses.

11. EMPHYSEMA

a permanent dilation of the distal air spaces to the terminal bronchiole, usually with destruction of their walls and with termed overinflation.

12. LEATHER BOTTLE STOMACH

Its type of late gastric cancer which appear as diffusely infiltrating lesion that causes thickening and contraction of the stomach wall with relatively little mucosal involvement [linitis plastica] 13. RHEUMATIOD NODULE

ď&#x201A;ˇ It is a local swelling or tissue lump, usually rather firm to touch, like an unripe fruit, which occurs almost exclusively in association with rheumatoid arthritis. Very rarely rheumatoid nodules occur as rheumatoid nodulosis in the absence of arthritis. 14. MINIMAL CHANGE DISEASE

Minimal Change Disease (MCD, also known as Nil Lesions, Nil Disease, or lipoid nephrosis) is a disease of the kidney that causes nephrotic syndrome and usually affects children (peak incidence at 2â&#x20AC;&#x201C;3 years of age) 15. SILICOSIS

disease caused by inhalation of crystalline silicon dioxide (silica) dust particles in the range of 1-5 um. 16. PERIVASCULAR CUFFING

51 | P a g e

Consist of mononuclear cell including lymphocyte and macrophage 17. ASCOFF BODY o The hallmark of acute rheumatic carditis is the presence of multiple foci of inflammation within the connective tissue of heart called Aschoff bodies. o The Aschoff body is fusiform, the cytoplasm of the component cell is diminished in amount and the cells become spindle shaped. The collagenous fibers fuse to small scars.

18. ONCOFETAL ANTIGENS

Are proteins that are expressed at high levels on cancerous cells and in normal developing (fetal tissues) 19. MYOCARDIAL INFARCTION

Myocardial infarction (MI) is refers to a discrete focus of ischemic necrosis in the heart Acute myocardial infarction  Heart attack 20. CONSOLIDATION

It is a region of (normally compressible) lung tissue that has filled with liquid, a condition marked by induration (swelling or hardening of normally soft tissue) of a normally aerated lung. - It is considered a radiologic sign. 21. BRONCHIECTASIS

It is abnormal and irreversible dilation of the bronchial tree proximal to the terminal bronchioles in contrast to emphysema, which involves the bronchial tree distal to the terminal bronchioles. 22. GROUND GLASS HEPATOCYTES

Its a histologic change in which hepatocytes infected with hepatitis B virus show this appearance “ground-glass” that contrasts with the coarsely granular cytoplasm of uninfected hepatocytes. 23. IgA NEPHROPHATY

> Also known as Berger Disease > Deposition of IgA in mesangium > Common manifestation is hematuria 24. COMEDOCARCINOMA

Comedocarcinoma is one kind of breast cancer which is most commonly very early-stage which demonstrates central necrosis. It is a usually a type of ductal carcinoma in situ 25. SOFTEN FOCCUS

> Liquefaction necrosis in Japanese B Encephalitis > Well circumscribed and pale stained incomplete necrotic area 26. KAPOSI’S SARCOMA

Malignant neoplasm of skin and internal organs 27. MESOTHELIOMA

52 | P a g e

a cancer of mesothelial tissue, associated especially with exposure to asbestos.

SHORT QUESTIONS 1.

WHAT FACTORS PRE-DESPOSE TO THROMBUS FORMATION IN LEG VEINS? WHAT ARE THE MAJOR COMPLICATIONS OF VENOUS THROMBI?

PATHOLOGICAL CHANGES OF VIRAL PNEUMONIA.

⁻ ⁻ ⁻ ⁻ ⁻ ⁻ ⁻ ⁻

Expanded alveolar septa edema ,hyperemia A cellular infiltrate by lymphocytes and plasma cells. The alveolar spaces are airfilled Infected alveolar epithelial cells Necrosis variety of inclusion bodies (cytomegalo virus, herpes virus, measles virus). Infected alveolar epithelial cells show multinucleated giant cells (respiratory syncytial virus, measles, herpesvirus).

DESCRIBE THE MORPHOLOGY OF COMPLETE MOLE.

GROSS  The uterus is usually enlarged.  The uterine cavity is filled with a mass of grape-like structures - thin-walled, translucent, cystic, and grayish-white.  This represents the hydatidiform mole.  No normal fetal parts are identified. MICROSCOPICALLY  the cysts are composed of hydropic chorionic villi, the interior being filled with an avascular, loose myxoid stroma.  Trophoblastic proliferation produces sheets of cytotrophoblastic and syncytotrophoblastic cells.  Cytologic atypia may be present. 4.

WHAT ARE THE POSSIBLE OUTCOMES OF ACUTE INFLAMMATION.

LONG QUESTIONS 1.

HOW TO REPAIR A BIG TISSUE DEFECT IN THE HUMAN BODY?

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WHAT IS LEUKEMIA? WHAT IS SARCOMA? WHAT IS TERATOMA?

LEUKEMIA :: Malignant haemopoietic tumor SARCOMA :: Malignant tumor of connective or other non-epithelial tissue TERATOMA :: Orginates from germ cells, eg:: gonad 3.

DIFFERENCE BETWEEN APOPTOSIS AND NECROSIS.

Cell death. There are two forms of cell deathnecrosis,the ultimate result of irreversible cell injury, and apoptosis(programmed cell death)

NECROSIS Pathological

STIMULI PATTERN OF DEATH HISTOLOGY DNA BREAKDOWN CELLULAR PROCESSES TISSUE REACTION

Group

APOPTOSIS Physiological and Pathological Single cells

Swelling Random

Condensation Diffuse inter-nucleosomal

ATP depletion

Endonucleases

Inflammation

4. DESCRIBE THE NOMENCLATURE OF TUMORS ? Nomenclature is 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 ⁻ Classified as ⁻ BENIGN TUMOR :: These are generally named after the cell of origin followed by the suffix -oma ⁻ Such as :: Fibroma, chondroma etc ⁻ MALIGNANT TUMOR :: CARCINOMA

SARCOMA



Malignant epithelial neoplasm



Malignant mesenchymal neoplasm



Epithelial  ROOT + CARCINOMA



Epithelial  ROOT + SARCOMA



Ex :: squamous carcinoma, adenocarcinoma



Ex :: Fibrosarcoma, Chondrosarcoma

5. LIST 4 KINDS OF SEXUAL TRANSMITTED DISEASE. EXPLAIN MAIN PATHOLOGICAL CHANGES. Disease Main pathological changes HPV(Human Pappiloma Virus)  condyloma acuminatum

HIV (Human immune deficiency Virus)  AIDS

1. SITES :: penis/vagina/cervix/vulva/perianal/perineum 2. NE :: clinical infection/subclinical infection 3. Koilocytosis (squamous cell perinuclear vacuole, heterochromic nucleus) 1. CHANGES OF LYMPH NODES 2. EARLY STAGE - PGL (persistent generalized lymphadenopathy) 3. LATE STAGE

Neisseria gonorrhoeae 

1. SUPPURATIVE ACUTE INFLAMMATION - Affected areas : urethra, prostate, epididymis, cervix 2. AFFECTED TISSUES - superficial layer of mucous membrane 3. OTHER ORGANS - genital tract, pelvic peritoneum: peritonitis, fetus

Treponema pallidum  syphilis

1. GUMMA (syphiloma :: localized destructive granuloma) 2. SMALL BLOOD VESSEL DISEASE

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6. d) e) -

PLEASE DESCRIBE THE RHEMATIC PATHOLOGICAL CHANGES IN HEART. EARLY PHASE [Exudative, degeneration] The initial tissue reaction is that of focal fibrinoid necrosis. PROLIFERATIVE PHASE [Granulomatous phase] The hallmark of acute rheumatic carditis is the presence of multiple foci of inflammation within the connective tissue of heart called Aschoff bodies. f) FIBROSIS PHASE [Healed phase] - The Aschoff body is fusiform, the cytoplasm of the component cell is diminished in amount and the cells become spindle shaped. The collagenous fibers fuse to small scars.

DESCRIBE THE CLINICAL FEATURES OF LIVER CIRRHOSIS. CHRONIC LIVER FAILURE  Decreased synthesis of albumin, low serum albumin levels, edema and ascites.  Decreased levels of Prothrombin and of factors VII, IX and X – a bleeding tendency.  Hepatic Encephalopathy :: It is characterized by cerebral dysfunction [hypersomnia, delirium, flapping tremors of hands] leading to convulsion, coma and death.  Hepato-renal syndrome :: Occurrence of acute renal failure  Endocrine changes :: Disordered metabolism of certain hormones, testicular atrophy and small vascular telangiectasia in the skin [spider angiomas]  Fetor hepaticus :: breathe like that of “a freshly opened corpse” due to deficient methionine  Jaundice and liver hand PORTAL HYPERTENSION : Causes :: Presinusoidal: Obstruction of intrahepatic / extrahepatic portal veins. Sinusoidal: Fibrosis and distortion of sinusoids, arterio-venous anastomoses. > Splenomegaly > Portosystemic shunt :: Development of Portosystemic venous anastomoses – bypassing the obstructed portal circulation. > Ascites

8. PLEASE DESCRIBE THE PATHOLOGICAL CHANGES IN HEART, KIDNEY AND BRAIN OF HYPERTENSION PROCESS. f) EARLY HYPERTENSION - The early phase hypertension is asymptomatic, and diagnosis can be made only by detecting the elevation of blood pressure. g) HYPERTENSIVE HEART DISEASE - The term hypertensive heart disease is used when the heart is enlarged in the absence of a cause other than hypertension. - CONCENTRIC HYPERTENSION - Left ventricular hypertrophy and normal size of the chamber. - With long – standing and severe hypertension left ventricular dilation and failure occurs. h) HYPERTENSIVE RENAL DISEASE - Changes in renal arterioles occur in most cases of hypertension, resulting in decreased glomerular filtration rate, progressive fibrosis and loss of nephrons in kidney. - Renal failure with elevation of serum creatinine usually occurs only in patients with malignant hypertension. i) HYPERTENSIVE CEREBRAL DISEASE - Hypertensive patients have a greatly increased incidence of cerebrovascular disease, both thrombosis and hemorrhages (strokes). j) HYPERTENSIVE RETINAL DISEASE - Narrow, irregular arteries with thickened walls characterize mild to moderate hypertension.

DESCRIBE THE PATHOLOGICAL CHANGES OF GASTRIC CARCINOMA.

 Early gastric cancer ⁻ gastric carcinoma restricted to the mucosa and submucosa ⁻ regardless of the presence or absence of perigastric lymph node metastases.

 Late gastric cancer ⁻ Fungating/polypoid type

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⁻ ulcerative type ⁻ Diffusely infiltrating type / leather-bottle stomach/ linitis plastica.

10. COMPARE TUBERCULOSIS, TYPHOID FEVER, BACILLARY DYSENTRY AND LEPROSY ACCORDING TO PATHOGENS, INFECTIVE PATHWAYS, SUSEPTIVE TISSUE OR ORGANS AND THE TYPICAL PATHOLOGICAL CHANGES. PATHOGENS INFECTIVE SUSPECTIVE TISSUE TYPICAL PATHOLOGICAL CHANGES PATHWAYS / ORGANS Mycobacterium Pulmonary, Human lungs Caseous necrosis, Fibrosis, TUBERCULOSIS tuberculosis intestinal, tonsillar, Epitheliod cells, Langhans gaint placenta, cell, Lymphocyte cutaneous Salmonella Fecal oral route Human colon Typhoid cell showing typhoid TYPHOID FEVER typhi granuloma. Hyperplasia stage, Necrotic stage, Ulcerative stage, Healing stage BACILLARY DYSENTRY LEPROSY

Shegilla colitis

Fecal oral route

Human colon

Pseudo membrane and ulcer

Mycobacterium leprae

Person to person with low infective rate

Skin & Peripheral Nervous system

Nodules, Virchow Lepra cell, Lucio’s phenomenon, Erythema nodosum leprosum

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PATHOLOGY EXAM PAPER 2013 BATCH TERMS. 1. Fatty change. 2. Metaplasia. 3. Edema. 4. Embolism. 5. Granulomatous inflammation. 6. Paraneoplastic lesion. 7. Rheumatism. 8. Atheromatous plaque. 9. Gray hepatization. 10. Chronic bronchitis. 11. Peptic ulcer disease. 12. Subcutaneous rheumatoid nodule. 13. Micro invasive carcinoma. 14. Tuberculoma. 15. Gumma.

SHORT QUESTIONS. 1. Membranous nephropathy morphology and clinical manifestation? 2. Outline the basic steps included in the extravasation of leukocytes in acute inflammation? 3. Pathological features of chronic corpulmonale?

LONG QUESTIONS. 1. 2. 3. 4. 5.

Explain the pattern of necrosis and its outcome? Pathophysiological feature of mitral stenosis? Explain tumor virus? And the tumor caused by them? Difference between primary pulmonary and secondary pulmonary tuberculosis? Pathological features of liver cirrhosis?

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