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PA24.{5,7} | Portal Hypertension & Hepatocellular Carcinoma — SDL Guide (Part 2)

Splenomegaly and Hypersplenism

Three-panel diagram showing normal versus congestive splenomegaly (Panel A), histological features including dilated sinusoids, haemosiderin deposition, and Gamna-Gandy bodies (Panel B), and the hypersplenism mechanism leading to pancytopenia with increased variceal haemorrhage risk (Panel C). — **Panel A:** Normal spleen (≈150 g) vs congestive splenomegaly (500–1000 g); splenic vein back-pressure arrow. **Panel B:** Dilated sinusoids, haemosiderin deposition (golden-brown macrophage granules), Gamna-Gandy bodies (calcified siderotic foci), fibrosis. **Panel C:** Oversized spleen trapping erythrocytes / leucocytes / platelets; outcome boxes: Anaemia, Leucopenia, Thrombocytopenia (Pancytopenia); variceal haemorrhage risk callout.

Sustained back-pressure in the splenic vein causes congestive splenomegaly. In portal hypertension, the spleen may reach 500–1,000 g (normal ≈ 150 g). Histologically: dilated sinusoids, haemosiderin deposition, fibrosis (Gamna-Gandy bodies = foci of organised old haemorrhage).

Hypersplenism is the clinical consequence: the enlarged spleen traps and destroys circulating blood cells excessively, causing pancytopenia — anaemia, leucopenia, and thrombocytopenia. A low platelet count in a cirrhotic patient almost always reflects hypersplenism. Paradoxically, thrombocytopenia combined with coagulopathy (reduced hepatic synthesis of clotting factors) severely worsens the risk of variceal haemorrhage.

Ascites — Mechanism

Diagram showing three pathways causing ascites in portal hypertension: raised hydrostatic pressure, hypoalbuminaemia, and RAAS-driven sodium and water retention converging on peritoneal fluid accumulation. — **Panel A:** Peritoneal cavity, liver, bowel loops, ascitic fluid, three converging pathways, SAAG formula and diagnostic threshold. **Panel B:** Portal venous congestion, raised sinusoidal hydrostatic pressure, fenestrated sinusoidal endothelium, space of Disse, plasma transudation toward liver surface. **Panel C:** Blood vessel, reduced plasma albumin, decreased oncotic pressure, outward fluid movement into interstitial/peritoneal space. **Panel D:** Splanchnic vasodilation, nitric oxide, reduced effective arterial blood volume, baroreceptors, RAAS, ADH, kidney sodium and water retention, aldosterone, spironolactone, salt restriction.

Ascites (free fluid in the peritoneal cavity) in portal hypertension is multifactorial and involves at least three reinforcing mechanisms.

Flow diagram showing three mechanisms of ascites formation: portal hydrostatic pressure, hypoalbuminaemia, and RAAS-mediated sodium and water retention converging on peritoneal fluid accumulation. — **Panel A:** Increased hydrostatic pressure; cirrhotic liver, portal vein, hepatic sinusoid, fenestrated sinusoidal endothelium, space of Disse, liver surface, mesenteric capillaries, plasma transudation arrow.. **Panel B:** Hypoalbuminaemia; damaged liver, reduced albumin synthesis, low plasma albumin, reduced oncotic pressure, fluid movement out of vessel.. **Panel C:** RAAS and sodium/water retention; splanchnic vasodilation, reduced effective arterial blood volume, baroreceptors, RAAS, ADH, kidney, aldosterone, sodium and water retention, expanded plasma volume.. **Panel D:** Ascitic fluid accumulation; liver, mesentery, bowel loops, peritoneal cavity, ascitic fluid, converging hydrostatic/oncotic/RAAS arrows, SAAG interpretation box..

Mechanism 1 — Increased hydrostatic pressure: Raised sinusoidal pressure drives plasma across the fenestrated sinusoidal endothelium into the space of Disse and then into the peritoneal cavity via the liver surface and mesenteric capillaries. This is the primary driver in early/moderate portal hypertension.

Mechanism 2 — Hypoalbuminaemia: The damaged liver synthesises less albumin. Reduced plasma oncotic pressure favours fluid movement out of vessels. This amplifies fluid accumulation.

Mechanism 3 — RAAS and sodium/water retention: Splanchnic vasodilation (NO-mediated) reduces effective arterial blood volume → baroreceptors activate RAAS and ADH → renal sodium and water retention → expands plasma volume → more fluid transudation into peritoneum. This peripheral vasodilation theory explains why diuretics (spironolactone targets aldosterone) and salt restriction are therapeutic.

Serum-Ascites Albumin Gradient (SAAG): SAAG = serum albumin − ascites albumin. SAAG ≥ 1.1 g/dL indicates portal hypertension as the cause (high specificity). SAAG < 1.1 g/dL suggests exudate causes (malignancy, TB peritonitis).

CLINICAL PEARL

SAAG in daily practice: In Indian hospitals, where both TB peritonitis and cirrhotic ascites are common, SAAG is your first discriminating test — cheap, reliable, calculated from two albumin levels. A SAAG ≥ 1.1 g/dL confidently points to portal hypertension. Do not miss the coexistence of TB + cirrhosis (SAAG may be intermediate 0.8–1.1 g/dL in these cases — always send ascitic fluid ADA and CBNAAT simultaneously).

Hepatic Encephalopathy

A four-panel diagram shows ammonia generated in the gut bypassing or overwhelming the liver, entering systemic circulation, crossing the blood-brain barrier, causing hepatic encephalopathy, and being treated with lactulose and rifaximin. — **Panel A:** Gut-derived ammonia, portal vein, liver, reduced hepatocellular mass, porto-systemic shunt, systemic circulation, blood-brain barrier, brain. **Panel B:** High-protein meal, gastrointestinal bleed, dietary/blood proteins, colonic bacteria, ammonia generation. **Panel C:** Asterixis/flapping tremor, confusion, drowsiness, coma, neuropsychiatric progression. **Panel D:** Lactulose, acidic colon, NH3 to NH4+ trapping, rifaximin, urease-producing bacteria suppression.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome caused by the liver's failure to metabolise gut-derived nitrogenous toxins — principally ammonia — that then enter the systemic circulation and cross the blood-brain barrier.

In portal hypertension, two factors converge:
1. Porto-systemic shunting — blood from the gut bypasses the liver through collaterals, delivering unmetabolised ammonia and other toxins directly to the systemic circulation.
2. Reduced hepatocellular mass — even blood that does pass through the liver encounters insufficient functioning hepatocytes to clear toxins.

Ammonia is converted by gut bacteria from dietary protein. This is why a high-protein meal or a GI bleed (where blood proteins become substrate for colonic bacteria) precipitates acute HE. Clinically: flapping tremor (asterixis), confusion, drowsiness, coma. Treatment targets gut ammonia: lactulose (acidifies colon, traps NH4+), rifaximin (suppresses urease-producing bacteria).