Hepatic stellate cell activation Quiescent Activated HSC HSC Autocrine tokine roliferation Smooth muscle cytokine Retinoid Y-actin Proliferative droplets cytokines (PDGH Fib cytokines stimulus (GEb) from Fibrogenesis Type NV Matrix collagenase nduced Initiation Perpetuation activation Phase Phase
Hepatic stellate cell activation
Liver fibrosis accumulation of synthesis degradation of matrix extracellular of matrix matrix in liver proteins proteins Collagens type I andⅢ constitute more than 95% of the total content of increased collagen in fibrotic liver
Liver fibrosis accumulation of extracellular matrix in liver synthesis of matrix proteins degradation of matrix proteins Collagens type I and III constitute more than 95% of the total content of increased collagen in fibrotic liver
THE HEPATIC PERISINUSOIDAL (DISSE)SPACE NORMAL FIBROTIC Collagen fibers Sinusoid Endothelial cell Sinusoid Lipocyte: Myofibroblast Low density matrix High density matrix LIPOCYTE- MYOFIBROBLAST
ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY OF LIVER FUNCTION NORMAL Sinusoid Central veIn Bile duct Portal v Hepatocyte Hepatic a FIBROTIC Fibrillar matrix Collagen bundle Basement membrane F igu Distortion of Capillarization Central Vein figure Veins by Septa of Sinusoids Sclerosis pane/)
Pathogenesis: chronic, progressed, diffuse Hepatocyte injury leading to necrosis Chronic inflammation-(hepatitis) Capillarization(肝窦毛细血管化) of the space of Disse is a key event ° Bridging fibrosis Regeneration of remaining hepatocytes proliferate as round nodules surrounded by fibrous septa Loss of vascular arrangement results in regenerating hepatocytes ineffective. Cirrhosis may lead to liver failure, portal hypertension, or development of hepatocellular carcinoma
Pathogenesis: chronic, progressed, diffuse • Hepatocyte injury leading to necrosis. • Chronic inflammation - (hepatitis). • Capillarization (肝窦毛细血管化) of the space of Disse is a key event. • Bridging fibrosis. • Regeneration of remaining hepatocytes proliferate as round nodules surrounded by fibrous septa. • Loss of vascular arrangement results in regenerating hepatocytes ineffective. • Cirrhosis may lead to liver failure, portal hypertension, or development of hepatocellular carcinoma