2012-9-27 BIOCHEMISTRY OF LIVER FUNCTION Metavir Scoring System for Fibrosis Centrel vi F3 F4 Scoring Systems for fibrosis Progression Histological“母“ F4(Cirrhosis) Non-cirmhotk Compensated Compensated Decompensated None(no varices) None varices G, magI Biological Fibrogenesis Scar and Thick (acelluar ngiogenesis X-linking Stage Pathophysiology Portal Hvpertension -Pathogenesis Pressure Flow x Resistance estruction of hepatocytes ncreased flow Flbrockyecarming (Splanchnic Vasculature) ncreased pressure in the venous and sinusoidal channel Modulable function injury contraction
2012-9-27 6 Metavir Scoring System for Fibrosis F1 F3 F2 F4 Modified from Poynard Scoring Systems for fibrosis Progression METAVIR Knodell Ishak F4 F4 F6 F3-F4 F3-F4 F5 F3 F3 F4 F2 F1-F3 F2-F3 F1 F1 F2 F0-F1 F0-F1 F1 F0 F0 F0 Friedman SL. Gastroenterology, 2008 Classification of chronic liver disease based on hisptological, clinical, hemodynamic, and biological parameters. Pathophysiology Etiology Alcohol abuse, Malnutrition, infection, drugs, Fatty infiltration, biliary obstruction… Portal hypertension Destruction of hepatocytes Fibrosis/scarring Liver function Injury Obstruction of blood flow Increased pressure in the venous and sinusoidal channel
2012-9-27 Consequences of portal hypertension Consequences of portal hypertension Formation and open of portal-systemic collateral's Formation and open of portal Esophageallgastric varices systemic collateral short gastric/coronary veins Splenomegaly Rectal collaterals uphemorrhoidal/middle inf Hemorrhoidal umbilical/epigastric bdominal wall varices
2012-9-27 7 Consequences of portal hypertension Formation and open of portalsystemic collateral’s Splenomegaly Ascites Consequences of portal hypertension Formation and open of portal-systemic collateral’s Esophageal/gastric varices short gastric/coronary veins Rectal collateral‘s Suphemorrhoidal/middle & inf. Hemorrhoidal Caput medusae umbilical/epigastric abdominal wall varices Portal system and left renal Esophageal varices Gastric varices Normal Gastro-esophageal varices bleeding Caput medusae ( umbilical)
2012-9-27 Consequences of portal hypertension Ascites Overflow theory abdominal wall varices Ascites enin angiotension aldosterone system RAAS Kallikrein-kinin system, Adenosine onal synthesis of PGs(PGE2 ? Renal tubular RAAS, Angiotension ll 一ET ↑ Plasma re Consequences of portal hypertension Pathology of Liver Cirrhosis Splenomegaly Other Organs vein varices: mucosal edema and stasis hypersplenism: anemia, leukopenia, peptic ulcer formation thrombocytopenia glomerulonephritis(membranous, anti-glumerulat ne, mesangial proliferative ilation of spenic sinus; proliferation of splenic pulp dilation of spleen artery, varicosity of splenic vein lomerulosclerosis, kidney tubules degenerative endophlebitis atrophy and degeneration
2012-9-27 8 abdominal wall varices Consequences of portal hypertension Ascites Theories of ascites formation • Underfilling theory • Overflow theory • Arterial vasodilation theory Ascites • Sodium retention --- Renin angiotension aldosterone system (RAAS) --- sympathetic nerve system , norepinephrine --- Intrarenal factors Kallikrein-kinin system, Adenosine • Water retention --- Antidiuretic hormone (ADH) --- Impaired renal synthesis of PGs (PGE2 ) • Renal vasoconstriction -- RAAS, Angiotension II -- SNS -- ADH -- ET Consequences of portal hypertension Splenomegaly Splenomegaly hypersplenism: anemia, leukopenia, thrombocytopenia spleen：splenomegaly; congestion; blood stasis, dilation of spenic sinus; proliferation of splenic pulp; dilation of spleen artery; varicosity of splenic vein; endophlebitis Pathology of Liver Cirrhosis Other Organs Gastrointestinal vein varices；mucosal edema and stasis； peptic ulcer formation Renal： glomerulonephritis（membranous, anti-glumerular basement membrane, mesangial proliferative glomerulonephritis） Glomerulosclerosis, kidney tubules degenetative necrosis Endocrine gland atrophy and degeneration