Pathology Tutorial 31 st batch

1. Pathology Tutorial 31st batch CARDIOVASCULAR SYSTEM

2. A patient is found to have a mid-diastolic murmur and is diagnosed as having mitral stenosis. He has a past history of Rheumatic fever. • List 2 other possible causes for mitral stenosis? (20) • List 2 complications of mitral stenosis? (20) • Describe the microscopic and macroscopic changes of the heart in acute rheumatic fever (50) • List 2 other organs / tissues involved in acute rheumatic fever (10)

3. Calcification Congenital heart disease Pulmonary hypertension Pulmonary oedema Right heart failure Atrial fibrillation Thrombo-embolism- cerebral/ renal/ peripheral/ intestinal infarction

4. Affects all three layers of the heart • Involvement of the endocardium • Heart valves become edematous (thickened) and loss the translucency. • Small multiple wart like vegetations seen along the line of closure. These are firmly attached to valvular leaflet and appear as irregular ridges of valve • left sided valves> right sided valves • On atrial surface of AV valves and ventricular surface of semilunar valves • Microscopically , Infiltration lymphocyte and plasma cells is diffuse; Aschoff bodies with central fibrinoid necrosis also seen. tiny (1-2mm) vegetation along the lines of closure of the heart valve. Vegetation contains fibrin and super added small thrombi (free of micro organism) • Mural endocarditis induces irregular thickenings of endocardial surface called MacCallum plaques

5. Myocarditis – ventricles becomes soft and flabby at early stage. microscopically aschoff bodies are characteristic. Aschoff body is foci of fibrinoid necrosis surrounded by anitschkow cells and multi nucleated aschff cells and infiltration of lymphocytes and plasma cells. • Loss of normal shiny and serofibrinous pericardial exudate in the pericardial sac described as "bread-and-butter" pericarditis. Microscopically contains fibrin deposits and cellular infiltrate mainly lymphocytes and plasma cells. Ashoff bodies may be seen. • joints/ skin /central nervous system

6. 2.1Define aneurysm (10) 2.2Classify aneurysms (40) 2.3Describe the clinical presentations of an abdominal aneurysm and the underlying pathological basis (50)

7. is a localized, abnormal dilatation of blood vessel / heart. • Classification of aneurysm • Depending on composition of wall • True aneurysm - when it involve all 3 layers of vessels/ heart • Atherosclerotic • Congenital • Infection – mycotic aneurysm ,Syphilitic • Inflammation - vasculitis • Ventricular aneurysm follows transmural MI • False aneurysm - extra vascular hematoma that freely communicate with the intravascular space • Usually due to trauma • Depending on their shape and size • Saccular aneurysm – spherical out pouching • Fusiform– diffuse circumferential dilatation of long segment of vessel

8. Clinical presentation AAA and its pathological basis (compression, rupture and thrombo embolic phenomena and arterial occlusion) • Pulsating abdominal mass • Backache – compression of nerves / erosion of vertebra, • Ureteric colic – compression of ureter • Abdominal pain, distension, pallor- leaking aneurysm irritates the peritoneum • Hypovolumic shock – rupture leads to massive intra abdominal heamorrage • Acute onset severe pain in lower limb , pulse less , pale/ gangrene -Limb ischemia due to thrombo embolism • Abdominal pain , vomiting – intestinal ischemia due to mesenteric artery occlusion by emboli • Heamaturia – renal infarct / erosion of ureter

9. 3.1 Discuss the serum enzyme changes in myocardial infarction (40) 3.2 What type of necrosis would you see in a myocardial infarction (10) 3.3 Describe the macroscopic and microscopic appearance of myocardial infarct (30) 3.4 List 4 possible complications that can occur after myocardial infarction? (20)

13. Coagulative necrosis • Macroscopic and microscopic appearance depends o age of the infarct • MI less than12 hours - not apparent macroscopically • 12- 24 hours – reddish blue in colour due to stagnated blood. • 48 -72 hrs-Progressively becomes pale and • 3- 7 days - more sharply demarcated yellow , soft area • 10 – 14 days infarct is rimmed by hyperemic area • 4-6 weeks – grey and become contracted thin fibrous scar. • microscopic • Coagulative necrotic features seen in 4 to 12 hours, odemaheamorrage few neutrophils • At the periphery of infarct – wavy fibers seen • Sub lethal cells at the periphery shows myocyte vacuolization • In 1 -3 days – acute inflammation dense PMNL infiltration • 5-10days – macrophages remove cell debris • 2-3 weeks – granulation tissue with loose collagen and abundant capillaries • 4- 6 weeks – become less cellular and decreased vascularity. • 8weeks - collagenous scar

14. Complications • Cardiogenic shock due to impaired contractility • Congestive heart failure • Arrhythmias • mitral regurgitation due to papillary dysfunction • Ventricular septal defect due to myocardial rupture • Pericarditis • Mural thrombus and emboli • Dressler’s syndrome • Ventricular aneurysm • Progressive late heart failure

15. Explain the pathological basis presence of embolic phenomenon in infective endocarditis and absence in rheumatic endocarditis (25) • Infective endocarditis • Forms friable bulky and potentially destructive vegetation on the heart valves, vegetation contains micro organisms • Rheumatic endocarditis • Cardiac manifestation of rheumatic fever associated with inflammation of the endocardium which results valvular deformities • vegetations are small 1-2 mm that are firmly attached to the valves

16. 4. Write short notes on the macroscopic appearance of heart in 4.1 Acute rheumatic fever (30) 4.2 Infective endocarditis (30) 4.3 Acute myocardial infarction (40)

17. Acute rheumatic fever • Affects all three layers of heart • Small vegetation along the site of closure of valves • Sub endothelial plaques may be seen • Diffuse involvement of myocardium leads to soft ,flabby myocardium • Pericardium- looses its shiny appearance; contain fibrinous or serofibrinousexudate in the pericardial sac gives bread and butter appearance , usually heals without any sequale

18. Infective endocarditis • Only the involve endocardium • Aortic and mitral valves are commonly affected • Forms friable bulky and destructive vegetation containing fibrin, inflammatory cells and microorganism • Size of vegetation varies with type of organism (few mm – cm) • Single /multiple • Potentially destructive • Can erode into myocardium and cause ring abscess

19. Acute myocardial infarction

20. 5. A patient is diagnosed to have acute rheumatic fever 5.1 Describe the pathological changes that could be seen in the heart of this patient? (50) 5.2 List 2 other causes for endocardial vegetation? (20) 5.3 Name 3 extra cardiac manifestations of rheumatic fever? (30)

21. It is type II hypersensitivity reaction which follows Group A streptococcus infection . • Causes inflammation of all three layers of heart • Discrete inflammatory lesion called aschoff bodies are the pathognomic lesion • Endocarditis - Involvement of the endocardium typically results in fibrinoid necrosis and tiny (1-2mm) vegetations along the lines of closure of the heart valve, which do not have much effect on cardiac function in acute phase • left sided valves> right sided valves • Mitral valve is affected commonly • subendothelial lesions may induce irregular thickenings called MacCallum plaques • Myocarditis - diffuse involvement of myocardium with aschoff bodies scattered in the intertitial space may lead to cardiac dilatation , arrhythmia and congestive heart failure • Pericarditis- contain fibrinous or serofibrinous exudates , heals without any sequale

22. Causes of endocardial vegetation • Infective endocarditis • Non bacterial thrombotic endocarditis • libman-sacks endocarditis • Extra cardiac manifestations • Migrating polyarthritis • Erythemamarginatum • Subcutaneous nodule • Rheumatic chorea

23. 6. A patient presenting with left sided chest pain of 48hours duration is diagnosed as having myocardial infarction. • 6.1 define infarction (10) • 6.2 What type of necrosis would you see in this patient? (10) • 6.3 Describe the macroscopy and microscopy of this patient’s infarct (30) • 6.4 List 2 biochemical investigations that would help in the diagnosis (20) • 6.5 List 4 possible complication this patient can develop (30)

24. Infarction • Necrosis of heart muscle due to ischemia • Coagulative necrosis • Macroscopy- infarcted area is soft yellow tan colour Microscpically – coagulative necrotic features ……….., with wavy fibers at the periphery • loss of nuclei and striation of myocytes, • neutrophil infiltrationin the intertitrial space • Serum Troponin I , CK-MB levels

25. Complications • arrhythmia • Pericarditis • Papillary muscle dysfunction results in mitral regurgitation • Myocardial rupture – VSD • Mural thrombus formation and thromboembolism • Later progressive heart failure

26. What is arteriosclerosis? It is a general term includes atherosclerosis, medial calcification (occur in old people), and arteriosclerosis Thickening and loss of elasticity is common feature

27. What is atherosclerosis? Large arteries and medium sized arteries Formation of atheroma in intima of vessels Can lead to obstruction and weakening of wall

28. Explain the pathogenesis of atherosclerosis / formation of uncomplicated atheroma. Several theory –cellular proliferation in the intima, repetitive thrombi formation and organization Response to injury theory - mostly accepted Chronic inflammatory process (of arterial wall) in response to endothelial injury. Risk factors – induces endothelial injury ( usually chronic )

29. Endothelial dysfunction • Increased permeability • Leucocytes adhesion • Accumulation of oxidized LDL in the sub endothelial space • Monocytes adhesion to endothelium and migration and transformation into macrophages • Factors released from activated platelet ,macrophages and vascular wall induces Smooth muscle cells recruitment to sub endothelium • Smooth muscle proliferates and produces collagen and other extra cellular matrix ( which forms the fibrous cap of the plaque) • macrophages engulf lipid and become as foam cell • Smooth muscle cells also take up lipid • Accumulation of intracellular and extra cellular lipid

30. Endothelial dysfunction Increased permeability Prothrombotic tendency Leucocyte ,monocyte, platelet adhesion Lipoprotein insudation Accumulation of EC lipids oxidization Release of chemical mediators Monocyte migration into sub endothelial space Migration of smooth muscle cell into intima Lipid taken up by macrophages and smooth muscle cells Proliferation of smooth muscle cells Deposition of ECM (collagen and proteoglycans) Fibrous cap Foam cells

31. Risk factors for atherosclerosis • Age • Male • Hyperlipidemia • Family history • Hypertension • Diabetes mellitus • Unhealthy diet ?? • smoking • Lack of exercise • Homocystinuria • obesity • Stressful life style

32. What is atherogenesis? Describe the appearance of a uncomplicated atherosclerotic plaque? Macroscopy Large vessel and medium sized artery, usually around the origin of branches. White-yellowish raised focal lesion on in the luminal surface Few mm-1-2cm Usually eccentric and multiple Soft core covered by firm fibrous tissue

33. New vessel

34. What are the complication of atherosclerotic plaque? Rupture , ulceration, and erosion Heamorrage into the plaque Athero embolism Critical stenosis Aneurysm formation due to atrophy of media Calcification

36. What is arteriolosclerosis? • Occurs in small vessels • Thickening of vessel lumen and narrowing • Causes ?? • Types • Hyaline arteriolosclerosis • Hyperpalstic arteriolosclerosis

37. Describe the pathogenesis of Hyaline arteriolosclerosis. • Chronic endothelial dysfunction /damage due to certain factors • Leakage of plasma • Excessive deposition of ECM by smooth muscle cells – hyaline thickening of arterioles,> luminal narrowing

38. Hyperplastic arteriolosclerosis • Occurs in malignant hypertension • Increased permeability of small vessels to fibrinogen and other plasma proteins • Platelet deposition at the site of injury • Plasma and platelet derived growth factors induces smooth muscle hyperplasia • Fibrinoid necrosis is also associated in malignant HT

39. Describe the vascular changes in systemic hypertension? Large and medium sized artery –atherosclerosis and degenerative changes Small vessels - arteriosclerosis