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MUHS 2nd MBBS Pathology - Complete Answer Set

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TOPIC 1: Pathways Leading to Systemic Oedema from Primary Heart Failure

• Failing left ventricle → back-pressure in pulmonary veins → pulmonary capillary hypertension → transudate leaks into alveoli → pulmonary oedema
• Clinical: dyspnea, orthopnea, paroxysmal nocturnal dyspnea, fine basal crepitations

• Back-pressure in systemic/portal veins → raised hydrostatic pressure
  • Raised portal pressure: congestive hepatomegaly (nutmeg liver), splenomegaly, ascites
  • Raised systemic venous pressure: dependent pitting oedema (ankles/feet), pleural effusion, pericardial effusion

• Reduced cardiac output → reduced renal perfusion → RAAS activation → aldosterone-driven Na⁺ and H₂O retention → increased plasma volume → further raised hydrostatic pressure → generalised oedema
• ADH (vasopressin) also released, worsening fluid retention
• As heart failure worsens, retained fluid increases hydrostatic pressure and perpetuates oedema

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TOPIC 2: Liver, Spleen in Right-Sided Heart Failure & Chronic Venous Congestion (CVC) of Lungs

LIVER - Right-Sided Heart Failure

• Liver enlarged and heavy (congestive hepatomegaly)
• Cut section: dark-red congested centrilobular (central vein) zones surrounded by paler, yellowish-tan peripheral parenchyma
• This alternating pattern = "Nutmeg liver" (resembles a cut nutmeg)
• In severe/long-standing cases: central areas become fibrotic → "Cardiac cirrhosis"

• Centrilobular sinusoidal dilatation and congestion (red cells engorging sinusoids around central vein)
• Central hepatocyte atrophy and necrosis (centrilobular necrosis) due to hypoxia - especially when left-sided failure also present
• Periportal hepatocytes survive longer (better oxygen from portal blood)
• Chronic cases: centrilobular fibrosis spreading outward → cardiac cirrhosis

SPLEEN - Right-Sided Heart Failure

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CHRONIC VENOUS CONGESTION (CVC) OF LUNGS

• Lungs heavy, firm, brown in colour ("brown induration of lung")
• On cut section: frothy, blood-tinged fluid exudes
• Lungs 2-3 times normal weight
• Subpleural petechiae may be visible

• Alveolar capillaries and septal vessels engorged with blood
• Alveolar walls thickened and fibrotic (congestion pneumonitis)
• Heart failure cells - alveolar macrophages laden with haemosiderin (from phagocytosed extravasated RBCs); these are pathognomonic
• Perl's Prussian blue stain demonstrates haemosiderin in macrophages
• Alveoli may contain RBCs and transudate fluid

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TOPIC 3: Difference Between Transudate and Exudate

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TOPIC 4: Oedema

Definition

• Anasarca = generalised massive oedema involving subcutaneous tissue, serous cavities
• Hydrothorax = pleural effusion; Hydropericardium; Ascites (peritoneal)

Types

1. Localised oedema - inflammatory, lymphatic, venous obstruction (DVT, tourniquet)
2. Generalised oedema (anasarca) - cardiac failure, nephrotic syndrome, hepatic cirrhosis
3. Pitting oedema - fluid shifts on pressure; in hypoproteinaemia, CCF
4. Non-pitting oedema - lymphoedema (myxoedema), lymphatic obstruction
5. Pulmonary oedema - fluid in alveoli/interstitium
6. Cerebral oedema - vasogenic or cytotoxic

Pathogenesis (Starling Forces)

• Forces pushing out of capillaries: hydrostatic pressure (capillary ~32 mmHg arterial end)
• Forces pulling back into capillaries: plasma colloid osmotic pressure (~25 mmHg, primarily albumin)
• Lymphatic drainage removes excess

Pulmonary Oedema - Pathophysiologic Mechanism

• Heavy, wet lungs (2-3× normal weight)
• Frothy, blood-tinged fluid on cut section
• Congested, dark red appearance

• Alveolar capillaries engorged
• Alveoli filled with homogeneous pink proteinaceous fluid (transudate)
• RBCs in alveolar spaces
• Heart failure cells (haemosiderin-laden macrophages) in chronic cases
• In ARDS: hyaline membrane formation lining alveolar walls

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TOPIC 5: Shock

Definition

Types, Mechanisms, Examples

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TOPIC 6: Stages of Shock

Stage 1 - NON-PROGRESSIVE (Compensated) Stage

• Baroreceptors detect ↓BP → reflex compensatory mechanisms activated
• Neurohumoral response:
  • Sympathetic stimulation → tachycardia, vasoconstriction
  • Catecholamine release (epinephrine, norepinephrine)
  • RAAS activation → angiotensin II → aldosterone → Na⁺/H₂O retention
  • ADH (vasopressin) release
  • ANP counterbalances (limited)
• Effect: Peripheral vasoconstriction (skin becomes pale, cool), coronary and cerebral blood flow maintained, blood shunted to vital organs
• Clinically: Patient is compensated; vital organs perfused; reversible if treated

Stage 2 - PROGRESSIVE Stage

• If underlying cause not corrected
• Widespread tissue hypoxia → anaerobic glycolysis → lactic acidosis
• Low pH blunts arteriolar vasomotor response → arterioles dilate → blood pools in microcirculation
• Peripheral pooling → further ↓ cardiac output → endothelial ischemia → DIC
• Vital organs begin to fail
• Clinically: acidosis, oliguria (ATN), confusion, falling BP despite vasopressors

Stage 3 - IRREVERSIBLE Stage

• Severe widespread cell injury
• Lysosomal enzyme leakage → autolysis
• Myocardial contractility worsens
• Ischaemic bowel allows intestinal bacteria into bloodstream → superimposed bacteraemic shock
• Acute kidney injury (ATN) = renal failure
• Multi-organ dysfunction syndrome (MODS)
• Death despite all interventions

Morphologic Changes in Shock

• Brain: ischaemic encephalopathy
• Heart: subendocardial necrosis, contraction band necrosis
• Kidney: acute tubular necrosis (ATN) - most classic finding; shock kidney
• Lungs: diffuse alveolar damage (ARDS) - "shock lung"
• Adrenals: cortical cell lipid depletion (stress response)
• GIT: haemorrhagic gastroenteropathy
• Liver: centrilobular necrosis ("nutmeg" pattern)

Note on Hypovolemic Shock

• Caused by loss of blood (haemorrhagic) or plasma (burns, diarrhoea)
• Stages clearly apply: compensated (tachycardia, vasoconstriction, oliguria) → progressive (acidosis, falling BP) → irreversible (MOF)
• Management: aggressive fluid resuscitation (crystalloid + blood products), control the source of bleeding
• Haemorrhagic shock classified by class I-IV (% blood volume lost)

Note on Septic Shock

• Most common cause: Gram-positive bacteria (Staphylococcus, Streptococcus), then Gram-negative (E. coli, Klebsiella), fungi
• Pathogenesis: LPS (endotoxin) and other PAMPs → Toll-like receptors on macrophages/endothelium → TNF-α, IL-1, IL-6, IL-12 → massive inflammatory response
• Effects: vasodilation (warm shock initially), ↑ vascular permeability, tissue hypoperfusion, DIC, metabolic derangements
• Superantigens (TSST-1) can cause toxic shock syndrome
• Mortality: 20-30%

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TOPIC 7: Thrombosis

Definition of Thrombus

Definition of Thrombosis

Pathogenesis - Virchow's Triad

• Exposes subendothelial collagen → platelet adhesion via vWF
• Exposes tissue factor (TF) → activates extrinsic coagulation cascade
• Endothelial activation: ↑ tissue factor, ↓ thrombomodulin, ↓ TFPI, ↑ PAI-1
• Causes: atherosclerosis, hypertension, hypercholesterolaemia, homocysteinaemia, smoking, inflammation, mechanical injury
• Predominates in arterial thrombosis

• Turbulence → endothelial injury/dysfunction; causes countercurrents, local stasis; disrupts laminar flow
• Stasis → platelets contact endothelium; prevents washing away of activated clotting factors; promotes endothelial hypoxia
• Predominates in venous thrombosis
• Examples: DVT (immobility), atrial fibrillation (stasis in atrial appendage), aneurysms, atherosclerosis (turbulence at bifurcations)

• Primary (genetic): Factor V Leiden mutation (most common), Prothrombin G20210A mutation, Protein C/S deficiency, Antithrombin III deficiency
• Secondary (acquired): Prolonged bed rest, pregnancy, OCP, cancer (Trousseau syndrome - migratory thrombophlebitis), antiphospholipid syndrome, nephrotic syndrome (loss of antithrombin III), HIT (heparin-induced thrombocytopenia)

Types of Thrombus

1. Arterial thrombus - white/pale, platelet-rich, at sites of turbulence (coronary, cerebral arteries); often occlusive
2. Venous thrombus (phlebothrombosis) - red/dark, RBC-rich, at sites of stasis (lower extremity deep veins); almost always occlusive; lines of Zahn present
3. Mural thrombus - in cardiac chambers or aorta (AF, MI, aneurysm); may embolise
4. Valvular vegetations - on cardiac valves (infective endocarditis = infected; NBTE = sterile; Libman-Sacks = SLE)

Gross Features of Thrombus

• Focally attached to vessel wall (at point of initiation)
• Arterial thrombus: pale, grey-white, friable, platelet-rich
• Venous thrombus: dark red, gelatinous, red cell-rich
• Lines of Zahn: alternating pale (platelet + fibrin) and dark red (RBC) laminations - hallmark of antemortem thrombus
• Propagating portion: poorly attached, prone to embolisation

Microscopic Features

• Pale areas: aggregated platelets + fibrin mesh
• Dark areas: entrapped RBCs and leukocytes
• Lines of Zahn clearly visible
• Attached to vessel wall at one end

Fate of Thrombus (4 possible fates)

1. Propagation - thrombus extends, increasing risk of occlusion/embolism
2. Embolisation - thrombus (or portion) dislodges → distant occlusion
3. Dissolution (thrombolysis) - plasmin digests fibrin; most favourable outcome
4. Organisation and recanalisation - ingrowth of endothelial cells, smooth muscle, fibroblasts → endothelialised channels form through the thrombus, partially restoring blood flow; becomes incorporated into vessel wall

Complications of Thrombosis

• Occlusion → ischaemia/infarction (MI, stroke, DVT-related limb ischaemia)
• Embolism → PE (from DVT), stroke (from cardiac mural thrombus)
• Cardiac mural thrombus → systemic embolism
• Phlegmasia cerulea dolens (massive DVT)
• Paradoxical embolism (venous thrombus crosses ASD/VSD to systemic circulation)

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TOPIC 8: Embolism

Definition of Embolus

Definition of Embolism

Types of Embolism with Examples

Pulmonary Thromboembolism (PTE)

• Massive (>60% occlusion) - sudden death, acute right heart failure (cor pulmonale), cardiovascular collapse
• Medium-sized - pulmonary haemorrhage (bronchial circulation usually prevents infarction); infarction if bronchial supply also compromised (e.g., left heart failure)
• Small/multiple - may be silent; organised into fibrous webs; recurrent emboli → pulmonary hypertension
• Saddle embolus - straddles pulmonary artery bifurcation → catastrophic

• Haemorrhagic, wedge-shaped, with base toward pleura and apex toward the occluded vessel (red infarct due to dual blood supply + congestion)
• Microscopy: coagulative necrosis, haemorrhage, congestion

Air Embolism

• Cause: Rapid entry of air into venous system (obstetric procedures, IV injection, neck trauma, open cardiac surgery); decompression sickness (Caisson disease) - rapid ascent from high pressure → dissolved N₂ forms gas bubbles in blood and tissues
• Amount needed: >100 mL can be fatal; even 5 mL can cause death in coronary or cerebral circulation
• Effects: Air lock in right ventricle → obstructs outflow → cardiac failure; cerebral/coronary embolism
• Decompression sickness ("bends"): N₂ bubbles in muscles/joints (pain), spinal cord (paralysis), lungs (chokes), brain (cerebral symptoms)
• Treatment: Hyperbaric oxygen (recompression)

Fat Embolism

• Cause: Fractures of long bones, liposuction, severe burns, pancreatitis
• Fat globules from bone marrow enter torn venules → travel to lungs → pulmonary insufficiency
• Triad: Respiratory distress, neurological symptoms (confusion, coma), petechial rash (thrombocytopenia from fat-induced platelet aggregation)
• Microscopy: Fat globules in pulmonary capillaries (stained with Sudan IV or Oil Red O)

Amniotic Fluid Embolism

• Rare but often fatal
• Squamous cells + mucin + lanugo from amniotic fluid enter maternal pulmonary vasculature → DIC + ARDS

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TOPIC 9: Infarct

Definition

Types of Infarct

Morphology of Infarcts

• Shape: Wedge-shaped, with occluded vessel at apex and organ periphery/serosal surface at base
• Fresh (0-24 hr): Poorly defined, slightly haemorrhagic, soft
• 1-2 days: Margins better defined by a rim of hyperaemia (congestion + acute inflammation)
• Days-weeks: Pale, yellow, increasingly well-defined (in solid organs); brown/dark (in lung - haemorrhagic)
• Long-standing: Replaced by grey-white fibrous scar (contracted)
• Overlying fibrinous peritonitis/pleuritis if serosal surface involved

• Main feature: Coagulative necrosis (ghost outlines of cells preserved; nuclei disappear - pyknosis → karyorrhexis → karyolysis)
• Changes take 4-12 hours to appear microscopically
• Acute inflammation at margins within hours, well-defined by 1-2 days
• Macrophages infiltrate to remove debris (4-5 days onwards)
• Granulation tissue forms (days to weeks)
• Fibrosis/scar formation (weeks to months)
• Exception: Brain → liquefactive necrosis (no coagulative necrosis)

Factors Influencing Development of Infarct

1. Anatomy of blood supply - end-arterial (kidney, spleen) = more susceptible; dual supply (lung, liver) = more resistant
2. Rate of occlusion - slow occlusion → collateral development → less infarction
3. Tissue susceptibility to ischaemia - neurons (4-5 min), cardiac myocytes (20-30 min), fibroblasts (hours-days)
4. Blood oxygenation - pre-existing anaemia/cyanosis worsens outcome

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Quick Summary Table for MUHS Revision

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