Tutorial 13: Liver Disease and Peptic Ulcer Disease

The liver receives a dual blood supply: the portal vein (approximately 75% of hepatic blood flow, carrying nutrient-rich blood drained from the gastrointestinal tract, spleen, and pancreas) and the hepatic artery (oxygen-rich systemic blood). Portal blood flows through liver sinusoids lined by hepatocytes before draining into central veins → hepatic veins → inferior vena cava. This portal circulation is pivotal to understanding portal hypertension.

Hepatic fibrosis and cirrhosis represent the end-stage of chronic liver injury from any cause (viral hepatitis B/C, alcohol, non-alcoholic steatohepatitis, autoimmune hepatitis, cholestatic disease). The central pathological cell is the hepatic stellate cell (Ito cell), which resides in the space of Disse (between hepatocytes and sinusoidal endothelium). In response to hepatocyte injury, Kupffer cells (hepatic macrophages) release pro-fibrotic cytokines (TGF-β, PDGF) that activate stellate cells, transforming them into myofibroblasts that deposit collagen in the space of Disse. Progressive collagen deposition distorts hepatic architecture, replacing parenchyma with fibrous septa that subdivide the liver into regenerative nodules — the hallmark of cirrhosis.

Cirrhosis complications arise from two mechanisms: (1) portal hypertension from increased resistance to portal blood flow through fibrotic liver → varices (oesophageal and gastric — life-threatening haemorrhage), haemorrhoids, caput medusae (dilated superficial abdominal veins from umbilical vein recanalisation), congestive splenomegaly and hypersplenism (thrombocytopenia, anaemia, leukopenia); (2) hepatocyte failure → coagulopathy (reduced factor synthesis), hypoalbuminaemia → ascites, hepatic encephalopathy (ammonia accumulation from reduced urea cycle activity + portosystemic shunting), and increased risk of hepatocellular carcinoma (HCC).

Alcoholic liver disease progresses through several stages. Alcoholic steatosis (fatty liver): excess ethanol → increased NADH:NAD ratio → impaired fatty acid oxidation + lipogenesis → intracellular lipid accumulation; reversible with abstinence. Alcoholic hepatitis: neutrophilic inflammation, hepatocyte ballooning degeneration, and Mallory-Denk bodies (intracytoplasmic tangles of intermediate filaments — ubiquitinated keratin); high short-term mortality in severe cases. Steatofibrosis/cirrhosis: progressive stellate cell activation and fibrosis; irreversible at cirrhosis stage.

Viral hepatitis: chronic HBV and HCV infection cause hepatocyte injury through immune-mediated mechanisms. Progression: periportal inflammation (hepatitis) → portal-portal bridging fibrosis → portal-central bridging septa → cirrhosis → HCC. HCV is directly cytopathic at high titres and also immune-mediated; effective direct-acting antiviral (DAA) therapy achieves >95% sustained virological response (SVR) and can halt progression.

Helicobacter pylori is a Gram-negative, spiral, urease-producing bacterium that colonises the gastric antrum. Urease generates ammonia from urea, neutralising gastric acid locally and allowing H. pylori to survive in the mucous layer. H. pylori causes type B gastritis (antral predominance), peptic ulcer disease (duodenal and gastric ulcers), and increases the risk of gastric adenocarcinoma and MALT lymphoma. Diagnosis: urea breath test, H. pylori stool antigen, or gastric biopsy (CLO test, histology). Treatment: triple therapy — a proton pump inhibitor (omeprazole) + clarithromycin + amoxicillin for 7–14 days — eradicates H. pylori and allows ulcer healing. NSAIDs are the second major cause of peptic ulceration (inhibit prostaglandin E₂, which normally stimulates mucus and bicarbonate secretion).