复旦大学附属中山医院：《内科学》课程教学资源（PPT讲稿）王吉耀 - 肝硬化 Hepatic Cirrhosis

Hepatic Cirrhosis Professor Wang Ji-yao Department of Internal Medicine Division of Gastroenterology, Zhongshan hospital, Fu Dan university

Hepatic Cirrhosis Professor Wang Ji-yao Department of Internal Medicine Division of Gastroenterology, Zhongshan hospital , Fu Dan university

Citthosis---definition chronic, progressed. diffuse hepatocellular injury fibrosis nodular regeneration ncidence: 17/100000/y Age: 20-50 yr

Cirrhosis---definition chronic, progressed, diffuse hepatocellular injury fibrosis nodular regeneration Incidence: 17/100000/y Age: 20-50 yr

Hepatic cirrhosis Etiology Diffuse, chronic liver injury Hepato-cellular Formation of regenerative necrosis, collapse of diffuse fibrous septa nodules formation 》 hepatic lobules Liver function Injury, Portal hypertension Complations: Upper GI Bleeding, Hepatic coma, infections, primary liver cancer, Functional renal failure

Hepatic cirrhosis 》 Etiology Liver function Injury,Portal hypertension Diffuse, chronic liver injury Hepato-cellular necrosis, collapse of hepatic lobules regenerative nodules formation Formation of diffuse fibrous septa Complations: Upper GI Bleeding, Hepatic coma, infections, primary liver cancer, Functional renal failure

Etiology of cirrhosis) 1 Chronic viral hepatitis(慢性病毒性肝炎 HBV,HCV,HBV+HDV 2 Long-term alcoholism(慢性酒精中毒) [80g/d,10y 13. Prolonged cholestasis(长期胆汁郁积, intra-and extra-hepatic: primary biliary cirrhosis, PBCI /[secondary biliary cirrhosis] 4. Drugs and toxins(药物和毒物) Itoxic hepatitis---chronic active hepatitis-- cirrhosis 5 Nonalcoholic steatohepatitis(NASH(非酒精性 脂肪性肝炎)

1.Chronic viral hepatitis (慢性病毒性肝炎): [HBV,HCV,HBV+HDV] 2. Long-term alcoholism(慢性酒精中毒) [80g/d, 10 yr.] 3. Prolonged cholestasis(长期胆汁郁积), intra-and extra-hepatic:[primary biliary cirrhosis, PBC] /[secondary biliary cirrhosis] 4. Drugs and toxins(药物和毒物) [toxic hepatitis---chronic active hepatitis--- cirrhosis] 5. Nonalcoholic steatohepatitis (NASH)(非酒精性 脂肪性肝炎) Etiology of cirrhosis(I)

Etiology of cirrhosis(II) 6. Hepatic venous outflow obstruction(肝血液循环 障碍) veno-occlusive disease, Budd-Chiari syndrome, constrictive pericarditis 7. Metabolic disorders(遗传代谢性疾病) hemochromatosis(血色病); Wilson' s disease(肝豆状核变性); 8 Autoimmune hepatitis(AH(自身免疫性肝炎) 9 Schistosomiasis(血吸虫病) 10. Cryptogenic(隐原性) 11. Mixed alcohol+virus. HBV+HCV, HBV+schistosomiasis

Etiology of cirrhosis(II) 6. Hepatic venous outflow obstruction(肝血液循环 障碍) veno-occlusive disease, Budd-Chiari syndrome, constrictive pericarditis 7. Metabolic disorders (遗传代谢性疾病) hemochromatosis(血色病);Wilson‘s disease(肝豆状核变性); 8. Autoimmune hepatitis (AIH)(自身免疫性肝炎) 9. Schistosomiasis (血吸虫病) 10. Cryptogenic (隐原性) 11. Mixed: alcohol+virus , HBV+HCV, HBV+schistosomiasis

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