ARCHITECTURAL LIVER DISRUPTION IS THE MAIN MECHANISM THAT LEADS TO AN INCREASED INTRAHEPATIC RESISTANCE,Liver Cirrhosis,Natural History,Cirrhosis,End stage of any chronic liver disease Characterized histologically by regenerative nodules surrounded by fibrous tissue Clinically there are two types of cirrhosis: Compensated Decompensated,DEFINITION OF CIRRHOSIS,Cirrhosis,Normal,Nodules,Irregular surface,GROSS IMAGE OF A NORMAL AND A CIRRHOTIC LIVER,Cirrhotic liver,Nodular, irregular surface,Nodules,GROSS IMAGE OF A CIRRHOTIC LIVER,Cirrhosis,Normal,Nodules surrounded by fibrous tissue,HISTOLOGICAL IMAGE OF A NORMAL AND A CIRRHOTIC LIVER,HISTOLOGICAL IMAGE OF CIRRHOSIS,Fibrosis,Regenerative nodule,PATHOGENESIS OF LIVER FIBROSIS,Hepatocytes,Space of Disse,Sinusoidal endothelial cell,Hepatic stellate cell,Fenestrae,Normal Hepatic SInusoid,Retinoid droplets,PATHOGENESIS OF LIVER FIBROSIS,Alterations in Microvasculature in Cirrhosis,Activation of stellate cells Collagen deposition in space of Disse Constriction of sinusoids Defenestration of sinusoids,Normal Liver,Hepatic vein,Sinusoid,Portal vein,Liver,Splenic vein,Coronary vein,THE NORMAL LIVER OFFERS ALMOST NO RESISTANCE TO FLOW,Portal systemic collaterals,Distorted sinusoidal architecture leads to increased resistance,Portal vein,Cirrhotic Liver,Splenomegaly,ARCHITECTURAL LIVER DISRUPTION IS THE MAIN MECHANISM THAT LEADS TO AN INCREASED INTRAHEPATIC RESISTANCE,AN INCREASE IN PORTAL VENOUS INFLOW SUSTAINS PORTAL HYPERTENSION,Mesenteric veins, Flow,Splanchnic vasodilatation,Distorted sinusoidal architechure,Portal vein,An Increase in Portal Venous Inflow Sustains Portal Hypertension,Mechanisms of Portal Hypertension,Pressure (P) results from the interaction of resistance (R) and flow (F):,Portal hypertension can result from: increase in resistance to portal flow and/or increase in portal venous inflow,MECHANISMS OF PORTAL HYPERTENSION,Compensated cirrhosis,Decompensated cirrhosis,Death,Chronic liver disease,Natural History of Chronic Liver Disease,NATURAL HISTORY OF CHRONIC LIVER DISEASE,Development of Complications in Compensated Cirrhosis,Ascites,Jaundice,Encephalopathy,GI hemorrhage,Probability of developing event,0,20,60,80,100,0,60,40,20,40,80,100,120,140,160,Months,Gines et. al., Hepatology 1987; 7:122,NATURAL HISTORY OF CIRRHOSIS,60,40,80,100,120,140,160,0,40,60,80,20,20,0,100,Months,Probability of survival,All patients with cirrhosis,Decompensated cirrhosis,180,Decompensation Shortens Survival,Gines et. al., Hepatology 1987;7:122,Median survival 9 years,Median survival 1.6 years,SURVIVAL TIMES IN CIRRHOSIS,Liver insufficiency,Variceal hemorrhage,Complications of Cirrhosis Result from Portal Hypertension or Liver Insufficiency,Cirrhosis,Ascites,Encephalopathy,Jaundice,Portal hypertension,Spontaneous bacterial peritonitis,Hepatorenal syndrome,COMPLICATIONS OF CIRRHOSIS,Cirrhosis - Diagnosis,Cirrhosis is a histological diagnosis However, in patients with chronic liver disease the presence of various clinical features suggests cirrhosis The presence of these clinical features can be followed by non-invasive testing, prior to liver biopsy,DIAGNOSIS OF CIRRHOSIS,In Whom Should We Suspect Cirrhosis?,Any patient with chronic liver disease Chronic abnormal aminotransferases and/or alkaline phosphatase Physical exam findings Stigmata of chronic liver disease (muscle wasting, vascular spiders, palmar erythema) Palpable left lobe of the liver Small liver span Splenomegaly Signs of decompensation (jaundice, ascites, asterixis),DIAGNOSIS OF CIRRHOSIS CLINICAL FINDINGS,Laboratory Liver insufficiency Low albumin ( 1.3) High bilirubin ( 1.5 mg/dL) Portal hypertension Low platelet count ( 1,In Whom Should We Suspect Cirrhosis?,DIAGNOSIS OF CIRRHOSIS LABORATORY STUDIES,CT Scan in Cirrhosis,Liver with an irregular surface,Splenomegaly,Collaterals,DIAGNOSIS OF CIRRHOSIS CAT SCAN,Diagnostic Algorithm,Patient with chronic liver disease and any of the following: Variceal hemorrhage Ascites Hepatic encephalopathy,Liver biopsy not necessary for the diagnosis of cirrhosis,Physical findings: Enlarged left hepatic lobe Splenomegaly Stigmata of chronic liver disease,Laboratory findings: Thrombocytopenia Impaired hepatic synthetic function,Radiological findings: Small nodular liver Intra-abdominal collaterals Ascites Splenomegaly Colloid shift to spleen and/or bone marrow,Yes,No,Yes,No,Liver biopsy,DIAGNOSTIC ALGORITHM,Liver insufficiency,Variceal hemorrhage,Complications of Cirrhosis Result from Portal Hypertension or Liver Insufficiency,Cirrhosis,Ascites,Encephalopathy,Jaundice,Portal hypertension,Spontaneous bacterial peritonitis,Hepatorenal syndrome,COMPLICATIONS OF CIRRHOSIS,Cirrhosis is the most common cause of portal hypertension The site of increased resistance in cirrhosis is sinusoidal Other causes of portal hypertension are classified according to the site of inc