hepatic sinusoid

STRUCTURE AND FLOW - Blood flow: portal triad (portal vein + hepatic artery branches) -> sinusoids -> central vein -> hepatic vein -> IVC. Bile flows the opposite way, through canaliculi toward the bile duct in the portal triad (countercurrent). - Wall: discontinuous, fenestrated endothelium with no diaphragm and no true basement membrane. Large gaps let albumin and lipoproteins pass, but not blood cells. - Space of Disse (perisinusoidal space): lies between the endothelium and hepatocytes. It is the site of plasma-hepatocyte exchange. Hepatocyte microvilli project into it.

CELLS ASSOCIATED WITH SINUSOIDS - Endothelial cells: fenestrated. They act as a filter and scavenge some molecules. - Kupffer cells: liver-resident macrophages (derived from yolk sac/monocytes) in the sinusoid lumen. They phagocytose bacteria, debris, and old RBCs, and they release cytokines (TNF-alpha, IL-1, IL-6) in sepsis and alcoholic hepatitis. - Hepatic stellate (Ito) cells: in the space of Disse. They store vitamin A (retinol) in lipid droplets. When injured, they become myofibroblasts and lay down collagen (types I and III), which causes fibrosis and cirrhosis. This is the key step in cirrhosis. - Pit cells: liver-specific NK cells.

ZONES OF THE ACINUS (Rappaport) - Zone 1 (periportal): closest to the oxygenated blood supply. It is most susceptible to viral hepatitis and to toxins that arrive by the portal route (e.g., phosphorus). It is the last zone to be affected by ischemia. Gluconeogenesis, urea synthesis, and beta-oxidation occur here. - Zone 2 (intermediate): affected in yellow fever. - Zone 3 (centrilobular, near the central vein): lowest oxygen. It is the most susceptible to ischemia (e.g., hypoperfusion or shock liver) and to toxins made by CYP450 (acetaminophen, CCl4, alcohol). It has the highest CYP450 content and is the first zone to show alcoholic hepatitis and congestion (nutmeg liver). Glycolysis and lipogenesis occur here.

CLINICAL CORRELATES - Portal hypertension: increased sinusoidal resistance (cirrhosis; "sinusoidal" cause) leads to varices (esophageal, caput medusae, hemorrhoids), splenomegaly, and ascites. Causes by location: presinusoidal (schistosomiasis, portal vein thrombosis), sinusoidal (cirrhosis), postsinusoidal (Budd-Chiari syndrome, right heart failure, constrictive pericarditis, veno-occlusive disease). - Budd-Chiari syndrome: hepatic vein thrombosis leads to sinusoidal congestion and centrilobular necrosis, with hepatomegaly, ascites, and abdominal pain. It is associated with polycythemia vera, hypercoagulable states, and OCP use. - Sinusoidal obstruction syndrome (veno-occlusive disease): sinusoidal endothelial injury after hematopoietic stem cell transplant or pyrrolizidine alkaloid (bush tea) exposure. It presents with painful hepatomegaly, jaundice, and weight gain/ascites. - Peliosis hepatis: blood-filled cavities from sinusoidal dilation. It is associated with anabolic steroids, OCPs, and Bartonella henselae (bacillary angiomatosis) in HIV. - Hepatic congestion (right heart failure): "nutmeg liver" from centrilobular congestion and necrosis. - Extramedullary hematopoiesis can occur in sinusoids (e.g., myelofibrosis). - Capillarization of sinusoids (loss of fenestrae, deposition of a basement membrane) in chronic liver disease impairs exchange and contributes to hepatic dysfunction. - Hepatocellular carcinoma: tumor vessels become capillarized and arterialized, which produces the arterial enhancement and washout pattern on imaging.

HIGH-YIELD PEARLS - Sinusoids are not lined by a continuous endothelium, so albumin and other macromolecules are easily exchanged. This allows protein-rich ascites in postsinusoidal (hepatic venous outflow) obstruction (SAAG >1.1 with ascitic fluid protein >2.5 g/dL) versus protein-poor ascites in cirrhosis (sinusoidal; SAAG >1.1, protein <2.5 g/dL). - Sinusoidal pressure is normally low (~ 2–5 mmHg). Portal hypertension is defined as a hepatic venous pressure gradient >5 mmHg, and clinically significant at ≥10 mmHg.