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Derangements of Homeostasis and Haemodynamics - MUHS Important Answers

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SHORT NOTES (SN)

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SN 1 - INFARCT AND ITS TYPES

• Occurs in:
  • Tissues with dual blood supply (lung, small bowel)
  • Loose/spongy tissues (lung) where blood can seep in
  • Venous occlusion (e.g., ovarian torsion)
  • Re-perfused areas (e.g., after thrombolysis in heart/brain)
• Gross: Wedge-shaped, red/hemorrhagic, base towards periphery, apex pointing to hilum
• Example: Pulmonary infarct, intestinal infarct

• Occurs in:
  • Solid organs with end-arterial supply (heart, kidney, spleen)
  • Where collateral blood supply is absent
• Gross: Wedge-shaped, pale/yellowish, firm, surrounded by a rim of congestion/hemorrhage
• Example: Myocardial infarct, renal infarct, splenic infarct

• Infected thrombus or embolus lodges in vessel
• Subsequent bacterial infection converts infarct into an abscess
• Example: Infective endocarditis producing septic emboli

• Coagulative necrosis - cell outlines preserved but nuclei lost (pyknosis, karyorrhexis, karyolysis)
• Surrounding zone of acute inflammation
• Later: granulation tissue, fibrosis, and scar formation

1. Nature of blood supply (dual vs end-artery)
2. Rate of occlusion (gradual = time for collateral formation)
3. Tissue vulnerability to hypoxia (neurons most sensitive - 3-4 min; myocardium - 20-30 min)
4. Oxygen content of blood (anemia worsens outcome)
5. Presence of pre-existing disease (atherosclerosis, stenosis)

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SN 2 - GROSS AND MICROSCOPIC FEATURES OF LIVER AND SPLEEN IN RIGHT-SIDED HEART FAILURE

LIVER

• Enlarged, heavy, tense capsule, cyanotic (blue-red discoloration)
• Rounded edges
• Cut surface: variegated mottled red-brown appearance - centrilobular congested areas (dark red) surrounded by pale periportal hepatocytes = "NUTMEG LIVER" (resembles cut surface of a nutmeg)
• If left-sided failure also present: necrotic central areas become depressed

• Acute congestion: Centrilobular sinusoids dilated and engorged with blood; centrilobular hepatocytes compressed and undergoing necrosis
• Chronic passive congestion: Centrilobular hepatocytes atrophied, liver cell plates markedly thin
• Periportal hepatocytes (closer to hepatic arterioles) are relatively spared, may show fatty change
• Combination of retrograde congestion + hypoperfusion = centrilobular hemorrhagic necrosis
• Sustained chronic heart failure: centrilobular fibrosis = "cardiac sclerosis" - may rarely progress to cardiac cirrhosis

The combination of left + right failure acts synergistically causing centrilobular hemorrhagic necrosis. The nutmeg appearance reflects hemorrhage and necrosis in centrilobular regions vs tan periportal hepatocytes.

SPLEEN

• Enlarged (congestive splenomegaly)
• Dark red, firm
• Tense capsule

• Dilated, congested sinusoids
• Thickened sinusoidal walls (fibro-siderotic changes in long-standing congestion)
• Red pulp congestion
• Hemosiderin deposits in macrophages (from red cell breakdown)
• Follicles may be compressed and small

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SN 3 - VIRCHOW'S TRIAD - ROLE IN THROMBUS FORMATION

1. Endothelial injury exposes subendothelial matrix - platelets adhere via GpIb-vWF interaction - platelet activation and aggregation - primary plug - then coagulation cascade activation via tissue factor - fibrin clot formation
2. Stasis prevents washout of activated clotting factors, allows platelet contact with endothelium, causes local hypoxia that injures endothelium
3. Turbulence causes endothelial injury and creates countercurrents that allow platelet aggregation

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SN 4 - AIR EMBOLISM

• Occurs in divers, tunnel workers, hyperbaric chamber workers
• On rapid ascent (decompression): nitrogen dissolved in blood/tissues rapidly comes out of solution as bubbles
• Gas bubbles form in skeletal muscle/joints (bends - severe joint pain), lungs (chokes - respiratory distress), brain/spinal cord (neurological deficits)
• Treatment: Slow decompression or hyperbaric O2 chamber (re-dissolves nitrogen)
• Chronic: Aseptic necrosis of femoral heads (avascular necrosis)

• Surgical procedures (neurosurgery in sitting position), IV catheter insertion (accidentally introducing air), chest trauma, obstetric procedures
• Air introduced into venous system
• Small amounts (< 100 mL) usually tolerated
• Large amounts (> 150 mL) can cause sudden death - air lock in right ventricle/pulmonary artery

• Air bubbles accumulate in right ventricle - frothy blood cannot be pumped effectively - cardiac output falls - sudden death ("air lock")
• Pulmonary capillary obstruction - V/Q mismatch - hypoxia

• Mill-wheel murmur (churning sound over precordium from air in right ventricle)
• Sudden hypotension, cyanosis, dyspnea
• Death in massive embolism

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SN 5 - PULMONARY THROMBOEMBOLISM

• 95% arise from DVT of deep veins of legs (popliteal vein and above)

• Right heart thrombi (rare)
• Pelvic veins (in obstetric patients)

1. Acute rise in pulmonary artery pressure (blockage + vasospasm from thromboxane A2, serotonin release)
2. Ischemia of downstream pulmonary parenchyma

• Occurs in only ~10% of PTE (dual blood supply of lung from pulmonary + bronchial arteries is protective)
• Infarction occurs when there is concurrent cardiac failure or poor bronchial circulation
• Gross: Wedge-shaped, hemorrhagic, base toward pleura
• Micro: Coagulative necrosis of alveolar walls with hemorrhage

• V/Q mismatch
• Atelectasis (reduced surfactant)
• Decreased cardiac output (widened A-V O2 difference)
• Right-to-left shunt through patent foramen ovale (30% of people)

• Organization and recanalization by fibrinolysis
• Pulmonary hypertension if recurrent

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LONG ANSWER QUESTIONS (LAQ)

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LAQ 1 (Med Mayur IMP) - CLINICAL CASE: CHF WITH PULMONARY EDEMA + CIRRHOSIS WITH BILATERAL ANKLE SWELLING

65-year-old chronic heart failure with sudden breathlessness, frothy pink sputum, crackles. Autopsy: heavy, wet lungs with fluid oozing from cut surface.

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A. OEDEMA - DEFINITION, TYPES, AND PATHOGENESIS

• Hydrothorax = pleural cavity
• Hydropericardium = pericardial cavity
• Hydroperitoneum (Ascites) = peritoneal cavity
• Anasarca = severe generalized oedema with widespread subcutaneous and body cavity fluid accumulation

• Vascular hydrostatic pressure (pushes fluid OUT of capillaries)
• Plasma colloid osmotic pressure (oncotic pressure, pulls fluid IN)
• At arteriolar end: hydrostatic > oncotic → fluid filters out
• At venular end: oncotic > hydrostatic → fluid returns
• Small net outflow is drained by lymphatics

• Pitting oedema: CHF, hypoproteinaemia, renal failure (watery transudate)
• Non-pitting oedema: Lymphoedema (protein-rich) or myxoedema (mucopolysaccharide deposits in hypothyroidism)

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B. PULMONARY OEDEMA IN PRIMARY HEART FAILURE - PATHOPHYSIOLOGY, GROSS AND MICROSCOPIC CHANGES

Left-sided heart failure
        ↓
Left ventricular pump failure → Reduced cardiac output
        ↓
Elevated left ventricular end-diastolic pressure (LVEDP)
        ↓
Back-pressure → Elevated left atrial pressure
        ↓
Elevated pulmonary venous pressure
        ↓
Transmitted to pulmonary capillaries → Elevated pulmonary capillary pressure
        ↓
Hydrostatic pressure exceeds plasma oncotic pressure
        ↓
Fluid leaks into interstitium (interstitial oedema)
        ↓
Lymphatics overwhelmed → Fluid enters alveolar spaces (alveolar oedema)
        ↓
PULMONARY OEDEMA

• RAAS activation (reduced renal perfusion) → Na+ and water retention → expands blood volume → worsens back-pressure
• Sympathetic activation → tachycardia, vasoconstriction → temporarily maintains BP but worsens cardiac work

• Lungs are heavy and wet (normal lung weight: ~400g each; in oedema can weigh 1000g or more)
• Frothy, pink-tinged fluid oozes from cut surface (fluid + air + a small amount of red cells from leaky capillaries)
• Lungs do not collapse normally on sectioning
• Congested, dark red appearance

• Blood-engorged alveolar capillaries (congestion)
• Alveolar septal widening (interstitial transudation)
• Pink homogeneous fluid in alveolar spaces (proteinaceous transudate)
• Variable intraalveolar hemorrhage (red cells in alveoli)

• Alveolar septa become thickened and fibrotic
• Alveolar spaces contain hemosiderin-laden macrophages = "Heart Failure Cells" (macrophages that have phagocytosed extravasated red cells, the hemoglobin being converted to hemosiderin)
• Prussian blue stain highlights hemosiderin granules in these macrophages
• Perivascular and peribronchial fibrosis

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C. TRANSUDATE vs EXUDATE

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LAQ 2 - EMBOLISM - DEFINITION, TYPES, PATHOGENESIS, MORPHOLOGICAL APPEARANCE, FATE

1. Pulmonary Thromboembolism (most common - see SN5 above)

2. Systemic Thromboembolism

• Source: Left-sided cardiac mural/valvular thrombi, aortic aneurysms, atherosclerotic plaques
• Sites: Lower extremities (75%), brain, intestines, kidneys, spleen
• Effect depends on: Site + alternative blood supply (collaterals)

3. Fat Embolism

• Pathogenesis: After crushing injury/fractures of long bones or severe burns → fat globules released into torn vessels → enter venous circulation → lodge in pulmonary microvasculature
• Also: Free fatty acids released → toxic endothelial injury
• Triad of Fat Embolism Syndrome: Pulmonary insufficiency (hypoxia, tachypnoea) + neurological symptoms + petechial rash (face/conjunctiva/axilla)
• Onset: 24-72 hours after injury
• Morphology: Fat globules in capillaries (stained by Sudan stain, Oil Red O)
• Prognosis: 10% mortality; may recover fully

4. Amniotic Fluid Embolism

• Rare but often fatal complication of labour/delivery
• Amniotic fluid + fetal debris enters maternal circulation via uterine tears or ruptured cervical veins
• Presents: Sudden dyspnoea, cyanosis, hypotensive shock, neurological symptoms, DIC (DIC because amniotic fluid is rich in procoagulant material including thromboplastin)
• Morphology: Squamous cells, lanugo hair, vernix, mucus in maternal pulmonary capillaries
• High maternal mortality (60-80%)

5. Air Embolism (see SN4 above)

6. Paradoxical Embolism

• DVT emboli cross from right to left heart through a patent foramen ovale (present in ~30% population) → systemic arterial embolism from a venous source

1. Lysis/Resolution - Fibrinolytic system dissolves small emboli
2. Organization - Fibroblasts invade; embolus becomes fibrous tissue
3. Recanalization - New channels form through the organized thrombus, partially restoring flow
4. Infarction - If vessel dependent territory has no collaterals
5. Perpetuation - If patient is hypercoagulable, fresh thrombus forms on organized embolus

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LAQ 3 - THROMBUS - DEFINITION, PATHOGENESIS, TYPES, FATE, COMPLICATIONS

1. Endothelial injury → subendothelial collagen and vWF exposed
2. Platelet adhesion via GpIb receptor binding to vWF
3. Platelet activation → release of ADP, TXA2, serotonin → shape change, more platelet recruitment
4. GpIIb-IIIa receptor activated → binds fibrinogen → platelet aggregation (primary plug)
5. Coagulation cascade: Tissue factor (factor VII) → → thrombin → fibrinogen to fibrin → stabilised clot
6. Thrombus propagates in direction of blood flow

1. Resolution/Lysis - Fibrinolytic activity dissolves small/recent thrombi (tPA activates plasminogen → plasmin → breaks down fibrin)
2. Organization - Ingrowth of fibroblasts, smooth muscle cells, endothelium from vessel wall into thrombus
3. Recanalization - Endothelium-lined channels form within organized thrombus, partially restoring blood flow
4. Propagation - Thrombus grows by additional clot deposition
5. Embolization - Fragment detaches and travels distally as an embolus (most dangerous fate)

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Sources: All content referenced from Robbins & Kumar Basic Pathology (Robbins Pathology, 9780323790185) and Fishman's Pulmonary Diseases and Disorders.

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• In LAQ, always write Definition → Pathogenesis → Morphology (Gross + Micro) → Clinical features → Fate/Complications
• "Lines of Zahn" and "Heart failure cells" are favourite one-liner MCQ/SN topics
• Virchow's triad is asked almost every year - memorise all 3 components with examples
• Difference between transudate and exudate (table format) scores full marks
• For liver in right heart failure: always mention "nutmeg liver" gross appearance and centrilobular congestion/necrosis microscopically
• Pulmonary oedema micro: emphasize "heart failure cells" (hemosiderin-laden macrophages) for chronic cases