CIRRHOSIS OF LIVER PORTAL HYPERTENSION HEPATIC ENCHEPALOPATHY PART-ONE 1 TO 21 slides

Definition of cirrhosis Cirrhosis is derived from Greek word kirros=orange or tawny and osis=condition -WHO definition :a diffuse process characterized by liver necrosis and fibrosis and conversion of normal liver architechture into structurally abnormal nodules that lack normal lobular organisation.

CAUSES OF LIVER CIRRHOSIS -Infections:post hepatitic cirrhosis(B,D,C). -Toxins:Alcohol. -Cholestatic liver disease:PBC,PSC… -Autoimmune diseases:autoimmune hepatitis. -Vascular disorders: cardiac cirrhosis,Budd-Chiari syndrome ,Veno occlusive disease -Metabolic and genetic :Wilson disease ,hemochromatosis,alpha 1- antitrypsin deficiency -Non alcoholic steato hepatitis(NASH). Cryptogenic.

Pathology of cirrhosis -nodularity(regenerating nodules). -fibrosis(deposition of dense fibrous septa)-fragmentation of sample. -abnormal liver architecture -hepatocyte abnormalities:pleomorphism,dysplasia,hyperplasia -Gross pathology:irregular surface ,yellowish colour,small,firm

HISTOLOGICAL IMAGE OF A NORMAL AND A CIRRHOTIC LIVER Cirrhosis Slide 8 HISTOLOGICAL IMAGE OF A NORMAL AND A CIRRHOTIC LIVER Histological images of two livers. On the left, a normal liver with conserved architecture. On the right, a cirrhotic liver with regenerative nodules surrounded by fibrous tissue (stained blue). Nodules surrounded by fibrous tissue

HISTOLOGICAL IMAGE OF CIRRHOSIS Fibrosis Regenerative nodule Slide 9 HISTOLOGICAL IMAGE OF CIRRHOSIS Histological image of a cirrhotic liver showing regenerative nodules surrounded by fibrous tissue (stained blue).

NATURAL HISTORY OF CHRONIC LIVER DISEASE Compensated cirrhosis Decompensated cirrhosis Death Development of complications: Variceal hemorrhage Ascites Encephalopathy Jaundice Slide 14 NATURAL HISTORY OF CHRONIC LIVER DISEASE Cirrhosis represents the end histological stage resulting from chronic liver injury of various etiologies. Initially, cirrhosis is compensated. The transition to a decompensated stage is marked by the development of variceal hemorrhage, ascites, hepatic encephalopathy and/or jaundice. Once decompensation occurs, the patient is at risk of death from liver disease.

CLINICAL FEATURES Hepatomegaly (although liver may also be small) Jaundice Ascites Circulatory changes Spider telangiectasia, palmar erythema, cyanosis Endocrine changes Loss of libido, hair loss Men: gynaecomastia, testicular atrophy, impotence Women: breast atrophy, irregular menses, amenorrhoea Haemorrhagic tendency Bruises, purpura, epistaxis, menorrhagia Portal hypertension Splenomegaly, collateral vessels, variceal bleeding, fetor hepaticus Hepatic (portosystemic) encephalopathy Other features Pigmentation, digital clubbing

COMPLICATIONS OF CIRRHOSIS Complications of Cirrhosis Result from Portal Hypertension or Liver Insufficiency Variceal hemorrhage Portal hypertension Spontaneous bacterial peritonitis Ascites Cirrhosis Hepatorenal syndrome Slide 17 COMPLICATIONS OF CIRRHOSIS Cirrhosis leads to two clinical syndromes: portal hypertension and liver insufficiency. Development of variceal hemorrhage and ascites are the direct consequence of portal hypertension, while jaundice occurs as a result of a compromised liver function. Encephalopathy is the result of both portal hypertension (portosystemic shunting) and liver dysfunction (decreased ammonia metabolism). Ascites in turn can become complicated by infection (spontaneous bacterial peritonitis) and by the development of a functional renal failure (hepatorenal syndrome). Encephalopathy Liver insufficiency Jaundice

Diagnosis of cirrhosis clinical+laboratory+radiologic+liver biopsy

DIAGNOSIS OF CIRRHOSIS – CLINICAL FINDINGS 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) Slide 19 DIAGNOSIS OF CIRRHOSIS – CLINICAL FINDINGS Cirrhosis should be investigated in any patient with chronic liver disease. Various physical signs suggest the presence of cirrhosis. In particular, a palpable left lobe with a small right lobe (on percussion) and splenomegaly are highly suggestive of cirrhosis. A recent review of several studies concludes that the listed physical findings, when present in chronic liver disease, confer a high specificity for cirrhosis. However the sensitivity is generally low and the absence of these physical signs does not exclude cirrhosis. De Bruyn G and Graviss EA, BMC Medical Informatics & Decision Making 2001; 1: 6

DIAGNOSIS OF CIRRHOSIS – LABORATORY STUDIES In Whom Should We Suspect Cirrhosis? Laboratory Liver insufficiency Low albumin (< 3.8 g/dL) Prolonged prothrombin time (INR > 1.3) High bilirubin (> 1.5 mg/dL) Portal hypertension Low platelet count (< 175 x1000/ml) AST / ALT ratio > 1 Slide 20 DIAGNOSIS OF CIRRHOSIS – LABORATORY STUDIES Tests that explore liver synthetic function are serum albumin and prothrombin time, while serum bilirubin investigates the ability of the liver to conjugate and excrete bilirubin. With liver dysfunction there is hypoalbuminemia,a prolonged prothrombin time and hyperbilirubinemia and the presence of either of these findings, in the presence of chronic liver disease, indicates the possibility of cirrhosis. However, an even earlier more sensitive finding suggestive of cirrhosis is a low platelet count that occurs as a result of portal hypertension and hypersplenism. An AST/ALT ratio >1 has also been identified as having a high specificity but a low sensitivity, therefore its absence cannot exclude cirrhosis. Poynard and Bedossa. J Viral Hepat. 1997; 4:199 Dienstag JL, Hepatology 2002; 36 (Suppl 1): S152

DIAGNOSIS OF CIRRHOSIS – CAT SCAN CT Scan in Cirrhosis Slide 23 DIAGNOSIS OF CIRRHOSIS – CAT SCAN This slide shows typical computed tomography findings in compensated cirrhosis. The contour of the liver is irregular, there is obvious splenomegaly and the presence of collaterals indicates portal hypertension and secures the diagnosis of cirrhosis. Liver with an irregular surface Collaterals Splenomegaly

Liver biopsy Diagnostic Algorithm Patient with chronic liver disease and any of the following: Variceal hemorrhage Ascites Hepatic encephalopathy Physical findings: Enlarged left hepatic lobe Splenomegaly Stigmata of chronic liver disease Laboratory findings: Thrombocytopenia Impaired hepatic synthetic function Yes No Radiological findings: Small nodular liver Intra-abdominal collaterals Ascites Splenomegaly Colloid shift to spleen and/or bone marrow Yes No Slide 41 DIAGNOSTIC ALGORITHM Diagnostic algorithm to investigate the presence of cirrhosis in patients with chronic liver disease. No Yes Liver biopsy not necessary for the diagnosis of cirrhosis Liver biopsy

Management of cirrhosis -Specific treatment in some pre cirrhotic lesions: Wilson’s disease—Dpenicillamine,,hemochromatosis---phlebotomy,,antiviral drugs for chronic viral hepatitis -in established cirrhosis---treatment of complications -screening for hepatocellular carcinoma -liver transplantation -maintenance of nutrition

CHILD-PUGH CLASSIFICATION OF PROGNOSIS IN CIRRHOSIS Score 1 2 3 Encephalopathy None Mild Marked Bilirubin (mg/dl) < 2.0 2.0-3.0 > 3.0 Albumin (g/dl) > 3.5 3.0-3.5 < 3.0 Prothrombin time (seconds prolonged) < 4 4-6 > 6 Ascites Add the individual scores: < 7 = Child's A 7-9 = Child's B > 9 = Child's C

MELD SCORE MELD = 3.8(SERUM BILIRUBIN –MG/DL)+11.2 IN INR + 9.6 IN SERUM CREATININE – MG/DL+ 6.4

PORTAL HYPERTENSION Definition:it is an increase in portal venous pressure. -normal portal pressure:5-10mmHg. -portal hypertension;>12mmHg -normal portal blood flow:1-1.5L/minute -- increased resistance to portal blood flow +hyperdynamic circulation-----formation of porto systemic collaterals that diver blood to systemic circulation bypassing the liver

MECHANISMS OF PORTAL HYPERTENSION Pressure (P) results from the interaction of resistance (R) and flow (F): P = R x F Portal hypertension can result from: increase in resistance to portal flow and/or increase in portal venous inflow Slide 44 MECHANISMS OF PORTAL HYPERTENSION In fluid mechanics, Ohm’s law states that pressure (P) is dependent upon flow (F) and resistance to flow (R). Therefore, portal hypertension can result from an increase in portal venous inflow, an increase in resistance to portal flow or an increase in both flow and resistance.