Cirrhosis is end-stage liver disease characterized by extensive fibrosis and architectural distortion, losing synthetic and detoxification functions. Portal hypertension develops from increased vascular resistance, triggering varices, ascites, and splanchnic vasodilation.
Understand the fibrotic cascade: chronic hepatocyte injury → hepatic stellate cell activation → myofibroblast proliferation → excessive collagen deposition. Study Child-Pugh and MELD scores as prognostic markers.
Cirrhosis is not reversible—antiviral therapy arrests progression but does not reverse established fibrosis. Portal hypertension precedes decompensation; compensated cirrhosis may be asymptomatic.
To understand cirrhosis, start with what the liver is supposed to do — and what happens when its architecture is destroyed. From your liver function prerequisite, you know the liver performs hundreds of tasks: synthesizing albumin and clotting factors, detoxifying ammonia to urea, conjugating bilirubin for biliary excretion, and metabolizing drugs and hormones. These functions depend not just on individual hepatocytes being alive, but on them being arranged in the correct spatial relationship to blood flow through the hepatic sinusoids. Cirrhosis destroys that architecture.
The fibrotic cascade begins with injury — whether from alcohol, viral hepatitis, steatohepatitis, or biliary obstruction — and your chronic inflammation prerequisite explains what follows: repeated cycles of hepatocyte death trigger a repair response. Hepatic stellate cells (HSCs), normally quiescent fat-storing cells in the perisinusoidal space of Disse, become activated by inflammatory cytokines (TGF-β is the dominant fibrogenic signal). Activated HSCs transdifferentiate into myofibroblasts: they contract, proliferate, and secrete massive amounts of Type I and III collagen. This collagen deposits in the perisinusoidal space, replacing the normal low-resistance fenestrated endothelium with a dense fibrous matrix — a process called capillarization of the sinusoids. The liver is now organized not into functional lobules but into regenerative nodules of hepatocytes surrounded by fibrous septa. This architectural distortion has two major consequences: hepatocytes lose direct access to blood flow (losing function), and vascular resistance through the liver rises sharply.
Portal hypertension follows directly from this increased vascular resistance. Portal venous pressure normally runs 5–10 mmHg; in cirrhosis it rises above 12 mmHg, which is the threshold at which complications develop. The portal system responds to back-pressure by developing portosystemic collaterals — new vascular channels that try to route blood around the liver. The most dangerous are esophageal and gastric varices: thin-walled vessels in the submucosa of the esophagus and stomach that balloon under portal pressure and can rupture catastrophically. Simultaneously, high portal pressure combined with low serum albumin (a synthetic failure) reduces oncotic pressure, pushing fluid from splanchnic vessels into the peritoneal cavity — the mechanism of ascites. Splanchnic vasodilation, driven by locally produced nitric oxide, worsens the situation by increasing portal blood flow even as resistance is already elevated.
The clinical course divides into compensated cirrhosis (portal hypertension present but collaterals manage it; patient may be asymptomatic for years) and decompensated cirrhosis (variceal bleeding, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome). Hepatic encephalopathy is driven primarily by ammonia — your liver function knowledge explains that the liver normally converts ammonia from gut bacterial metabolism to urea. When portosystemic shunting bypasses the liver, ammonia reaches the systemic circulation and the brain, impairing astrocyte function and producing neurological symptoms ranging from subtle personality changes to coma. The Child-Pugh and MELD scores you encounter in clinical training quantify the degree of synthetic failure (INR, albumin, bilirubin) and the portal hypertension complications (ascites, encephalopathy) to predict prognosis and prioritize transplantation — the only definitive therapy for end-stage disease.