Portal Hypertension

1. Anatomy of the Portal Venous System

Figure 124.1 — Anatomy of the portal venous system. (Yamada's Textbook of Gastroenterology, 7th ed.)

2. Pathophysiology

A. Increased Intrahepatic Resistance (primary mechanism in cirrhosis)

• Regenerative nodules and fibrotic bands compress and distort sinusoids
• Capillarization of sinusoids (loss of fenestrations)
• Swelling of hepatocytes and Kupffer cells

• Activated HSCs act as perisinusoidal pericytes and contract in response to vasoconstrictor stimuli
• ↓ nitric oxide (NO) production by endothelial cells → impaired vasodilation
• ↑ endothelin-1 (ET-1), angiotensin II → intrahepatic vasoconstriction
• Imbalance: vasoconstrictors dominate over vasodilators within the liver

B. Hyperdynamic Splanchnic Circulation (perpetuating factor)

• ↑ NO in splanchnic circulation (opposite to the liver: NO is increased here)
• Inflammatory mediators (bacterial translocation → PAMPs → cytokines)
• Increased production of prostacyclin and glucagon

• Increased splanchnic blood flow → increased portal inflow
• Reduced effective arterial blood volume → activation of RAAS and sympathetic nervous system → sodium retention → ascites
• Cardiac output is initially increased (hyperdynamic state); reduced at late stages

C. Collateral Circulation Development

3. Portosystemic Collaterals

Figure 124.3 — Sites of portosystemic collateral circulation in portal hypertension and cirrhosis. (Yamada's Textbook of Gastroenterology, 7th ed.)

A paraumbilical collateral vein is the most specific sign of intrahepatic (parenchymal) portal hypertension, as it indicates obstruction at the liver level rather than extrahepatic obstruction. — Yamada's Gastroenterology

4. Classification by Site of Obstruction

Note: HVPG measurement is only accurate for sinusoidal and postsinusoidal causes. In prehepatic/presinusoidal portal hypertension, HVPG is normal or only mildly elevated.

5. Causes of Portal Hypertension

Common

• Cirrhosis — accounts for the vast majority in the West (alcoholic liver disease, chronic viral hepatitis B/C, NAFLD/NASH, autoimmune hepatitis, hemochromatosis, Wilson's disease, PBC, PSC)
• Schistosomiasis — most common cause worldwide (presinusoidal); caused by S. mansoni or S. japonicum depositing eggs in presinusoidal portal venules → granulomatous inflammation → "pipestem fibrosis"

Less Common

• Portal vein thrombosis — associated with myeloproliferative neoplasms, hypercoagulable states, intra-abdominal infection, pancreatitis, malignancy
• Splenic vein thrombosis — causes "sinistral" (left-sided) portal hypertension; commonly due to pancreatitis
• Budd-Chiari syndrome — hepatic vein outflow obstruction; causes posthepatic portal hypertension
• Nodular regenerative hyperplasia — sinusoidal obliteration without fibrosis (associated with azathioprine, oxaliplatin, HIV)
• Sinusoidal obstruction syndrome — endothelial damage; associated with bone marrow transplantation, chemotherapy
• Congenital hepatic fibrosis — autosomal recessive; portal hypertension without liver failure
• Right heart failure / constrictive pericarditis — raised hepatic venous pressure transmitted back to sinusoids
• Arterioportal fistula — increased portal inflow

6. Clinical Features

A. Splenomegaly & Hypersplenism

• Elevated portal pressure in the splenic vein → splenomegaly
• Sequestration of blood cells → thrombocytopenia (most common and earliest), leucopenia, anaemia (pancytopenia = hypersplenism)

B. Ascites

• Triggered by splanchnic arterial vasodilation → effective arterial hypovolemia → RAAS & SNS activation → renal sodium retention
• Increased hydrostatic pressure in splanchnic capillaries (Starling forces) promotes transudation
• Hypoalbuminaemia reduces oncotic pressure

C. Variceal Hemorrhage

• Esophageal varices: most important; present in ~50% of cirrhotics; bleeding risk highest when HVPG > 12 mmHg; ~30% mortality per bleeding episode
• Endoscopic appearance: small (≤5 mm) vs. large (>5 mm); red wale marks, cherry red spots, hematocystic spots all indicate high bleeding risk
• Gastric varices (GOV1, GOV2, IGV1, IGV2 — Sarin classification): gastric fundal varices (IGV1) have highest bleeding risk
• Rectal varices (distinguished from hemorrhoids)

D. Caput Medusae

• Dilated paraumbilical veins radiating from the umbilicus
• Pathognomonic of intrahepatic portal hypertension

E. Hepatic Encephalopathy

• Portal blood (containing ammonia and other toxins) bypasses the liver through portosystemic shunts → toxins accumulate in systemic circulation → cross blood-brain barrier → astrocyte dysfunction, cerebral oedema
• Precipitated by infection, GI bleed, renal failure, constipation, excess dietary protein, benzodiazepines

F. Portal Hypertensive Gastropathy (PHG)

• Mosaic pattern of gastric mucosa on endoscopy; submucosal congestion without inflammation
• Can cause chronic occult bleeding

G. Hepatorenal Syndrome (HRS)

• Extreme renal vasoconstriction as a consequence of RAAS/SNS activation and reduced cardiac output
• Functional renal failure without structural kidney damage

H. Cardiopulmonary Complications

• Hepatopulmonary syndrome: intrapulmonary vascular dilatations → shunting → hypoxia; orthodeoxia (desaturation on sitting up)
• Portopulmonary hypertension: pulmonary arterial hypertension due to increased splanchnic mediators reaching the pulmonary circulation
• Cirrhotic cardiomyopathy: systolic dysfunction under stress, diastolic dysfunction, prolonged QT

I. Hepatic Hydrothorax

• Transdiaphragmatic passage of ascitic fluid (usually right-sided pleural effusion)

J. Haematological Features

• Coagulopathy (impaired synthesis of clotting factors)
• Anaemia (multifactorial: hypersplenism, variceal blood loss, poor nutrition)

7. Measurement of Portal Pressure

• HVPG (gold standard): WHVP − FHVP; measured via transjugular or femoral hepatic vein catheterization with balloon-occluding catheter
  • Normal: < 6 mmHg
  • Portal hypertension: ≥ 6 mmHg
  • CSPH: ≥ 10 mmHg (predicts variceal formation)
  • Variceal bleeding threshold: > 12 mmHg
• Non-invasive surrogates: liver stiffness (LSM) >20–25 kPa by elastography + low platelets + splenomegaly = CSPH
• HVPG is not accurate for prehepatic or presinusoidal causes

• Sleisenger and Fordtran's Gastrointestinal and Liver Disease, Chapter 92 (Shah & Kamath)
• Yamada's Textbook of Gastroenterology, 7th ed., Chapter 124 (Kamath & Wong Kee Song)
• Medical Physiology (Boron & Boulpaep)
• Mulholland & Greenfield's Surgery, 7th ed.