Hepatic stellate cell activation Quiescent Activated HSC HSC Autocrine cytokines Proliferation Smooth musel. Cytokine receptor Retinoid y-actin Proliferative droplets cytokines (PDGF Fibrogenic fIbrogenic younes stimulus IGEb Signal from Fibrogenesis Kuper cells ar Type NV Matrix collagenase diced Initiation Perpetuation activation ase Phase
Hepatic stellate cell activation
Liver fibrosis accumulation of synthesis degradation of matrix extracellular of matrix matrix in liver proteins proteins Collagens type i and l 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 ③9 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 Figu Distortion of Capillarization Central Vein gure Veins by Septa of Sinusoids Sclerosis pane/) elevate
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. oss 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