A 52-year-old man with a 20-year history of alcohol use disorder presents to the emergency department with haematemesis and melaena. On examination, he is hypotensive (BP 85/50), tachycardic (HR 118/min), and has clinical signs of chronic liver disease including spider angiomata, palmar erythema, and ascites. Laboratory investigations reveal INR 2.8, platelet count 65,000/μL, and total bilirubin 3.2 mg/dL. Upper endoscopy confirms bleeding oesophageal varices. What is the most likely underlying pathological mechanism responsible for the variceal bleeding in this patient?

Explanation

## Pathophysiology of Variceal Bleeding in Cirrhosis **Key Point:** Oesophageal varices in cirrhosis develop as a direct consequence of portal hypertension, which results from increased resistance to blood flow through the cirrhotic liver. ### Mechanism of Portal Hypertension in Cirrhosis In advanced cirrhosis, the normal hepatic architecture is replaced by fibrous tissue and regenerative nodules. This structural distortion: 1. Increases resistance to portal blood flow (increased intrahepatic vascular resistance) 2. Leads to portal pressure elevation (>12 mmHg defines clinically significant portal hypertension) 3. Causes portosystemic collateral formation, including oesophageal varices 4. Results in splanchnic vasodilation and increased portal blood flow, further perpetuating hypertension **High-Yield:** The hallmark of cirrhosis is loss of normal hepatic lobular architecture with replacement by fibrous septa and regenerative nodules — this is what causes the increased intrahepatic resistance. ### Clinical Features Supporting This Diagnosis This patient has multiple indicators of decompensated cirrhosis: - Ascites (portal hypertension + hypoalbuminaemia) - Thrombocytopenia (bone marrow suppression + splenic sequestration from splenomegaly) - Coagulopathy (synthetic dysfunction) - Variceal bleeding (portal hypertension) **Clinical Pearl:** The degree of portal hypertension correlates with the risk of variceal bleeding. Once portal pressure exceeds 12 mmHg, varices form; bleeding risk increases significantly when pressure >20 mmHg. ### Pathological Progression ```mermaid flowchart TD A[Chronic liver injury<br/>alcohol, HBV, HCV, etc.]:::outcome --> B[Hepatocellular necrosis<br/>and inflammation] B --> C[Hepatic stellate cell activation] C --> D[Excessive collagen deposition<br/>and fibrosis] D --> E[Loss of normal architecture<br/>Cirrhosis develops]:::outcome E --> F[Increased intrahepatic<br/>vascular resistance]:::action F --> G[Portal hypertension<br/>Portal pressure >12 mmHg]:::outcome G --> H[Portosystemic collaterals<br/>Oesophageal varices]:::outcome H --> I[Variceal rupture<br/>and bleeding]:::urgent ``` **Mnemonic:** **CIRRHOSIS** = **C**ollagen deposition → **I**ncreased resistance → **R**aised portal pressure → **R**egenerative nodules → **H**epatic dysfunction → **O**esophageal varices → **S**plenic sequestration → **I**nternational normalized ratio elevated → **S**planchnic vasodilation [cite:Robbins 10e Ch 18]