Pathology Tutorial 31st batch

• CARDIOVASCULAR SYSTEM

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)

• Calcification• Congenital heart disease

• Pulmonary hypertension• Pulmonary oedema• Right heart failure• Atrial fibrillation• Thrombo-embolism- cerebral/ renal/

peripheral/ intestinal infarction

• 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

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

• 2.1Define aneurysm (10)• 2.2Classify aneurysms (40)• 2.3Describe the clinical presentations of an

abdominal aneurysm and the underlying pathological basis (50)

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

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

• 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)

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, odema heamorrage 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

ComplicationsCardiogenic shock due to impaired contractilityCongestive heart failureArrhythmiasmitral regurgitation due to papillary dysfunctionVentricular septal defect due to myocardial rupturePericarditisMural thrombus and emboliDressler’s syndromeVentricular aneurysmProgressive late heart failure

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

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)

Acute rheumatic feverAffects all three layers of heartSmall vegetation along the site of closure of valvesSub endothelial plaques may be seenDiffuse involvement of myocardium leads to

soft ,flabby myocardiumPericardium- looses its shiny appearance; contain

fibrinous or serofibrinous exudate in the pericardial sac gives bread and butter appearance , usually heals without any sequale

Infective endocarditisOnly the involve endocardiumAortic and mitral valves are commonly affectedForms friable bulky and destructive vegetation

containing fibrin, inflammatory cells and microorganism

Size of vegetation varies with type of organism (few mm – cm)

Single /multiplePotentially destructiveCan erode into myocardium and cause ring abscess

• Acute myocardial infarction

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)

• Causes of endocardial vegetation– Infective endocarditis– Non bacterial thrombotic endocarditis– libman-sacks endocarditis

• Extra cardiac manifestations– Migrating polyarthritis– Erythema marginatum– Subcutaneous nodule– Rheumatic chorea

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)

• 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

Complications◦ arrhythmia◦ Pericarditis◦ Papillary muscle dysfunction results in mitral

regurgitation◦ Myocardial rupture – VSD ◦ Mural thrombus formation and thromboembolism◦ Later progressive heart failure

• 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

• What is atherosclerosis?• Large arteries and medium sized arteries• Formation of atheroma in intima of

vessels• Can lead to obstruction and weakening of

wall

• 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 )

Endothelial dysfunctionIncreased permeabilityLeucocytes adhesionAccumulation of oxidized LDL in the sub endothelial spaceMonocytes adhesion to endothelium and migration and

transformation into macrophagesFactors released from activated platelet ,macrophages and vascular

wall induces Smooth muscle cells recruitment to sub endotheliumSmooth 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 cellSmooth muscle cells also take up lipid Accumulation of intracellular and extra cellular lipid

Endothelial dysfunction

Lipoprotein insudation

Monocyte migration into

sub endothelial space

Migration of smooth muscle cell into intima

Prothrombotic tendency

Leucocyte ,monocyte, platelet adhesion

Release of chemical mediators

Lipid taken up by macrophages and

smooth muscle cells

Proliferation of smooth muscle cells

Deposition of ECM (collagen and

proteoglycans)Foam cellsFibrous

cap

Accumulation of EC lipids

oxidization

Increased permeability

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

• 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

New vessel

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

• What is arteriolosclerosis?• Occurs in small vessels• Thickening of vessel lumen and

narrowing• Causes ??• Types

– Hyaline arteriolosclerosis– Hyperpalstic arteriolosclerosis

• 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

• 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

• Describe the vascular changes in systemic hypertension?

• Large and medium sized artery –atherosclerosis and degenerative changes

• Small vessels - arteriosclerosis