CIRRHOSIS DR.AMANULLAH ABBASI FCPS, MRCP SENIOR REGISTRAR WARD-7 JPMC
Definition -Cirrhosis is characterized by a diffuse increase in the fibrous connective tissue of the liver, with areas of necrosis and regeneration of parenchymal cells, imparting a nodular texture histologically. -In its later stages, cirrhosis leads to such deformity of the liver that it interferes with hepatobiliary function and the circulation of blood to and from the liver
NORMAL LIVER
Cirrhosis
AETIOLOGY -Alcoholic liver disease (70%) alcoholic cirrhosis -Viral hepatitis (10%) post-necrotic cirrhosis -Cryptogenic cirrhosis (10%) unknown -Secondary biliary cirrhosis obstruction of bile duct -Primary biliary cirrhosis autoimmune disease -Primary sclerosing cholangitis (5%) Hereditary haemochromatosis(5%) -Cardiac failure cardiac cirrhosis -Wilson disease; α 1 -at deficiency (rare)
Pathophysiology of Cirrhosis -The liver plays a vital role in synthesis of proteins (e.g. albumin, clotting factors and complement), detoxification and storage (e.g. vitamin A). -In addition, it participates in the metabolism of lipids and carbohydrates. -Cirrhosis is often preceded by hepatitis and fatty liver (steatosis), independent of the cause. -If the cause is removed at this stage, the changes are still fully reversible.
Cont….. -The pathological hallmark of cirrhosis is the development of scar tissue that replaces normal parenchyma, blocking the portal flow of blood through the organ and disturbing normal function. -Recent research shows the pivotal role of stellate cell, a cell type that normally stores vitamin A, in the development of cirrhosis. -Damage to the hepatic parenchyma leads to activation of the stellate cell, which becomes contractile (called myofibroblast) and obstructs blood flow in the circulation.
Cont….. - In addition, it secretes TGF-β1, which leads to a fibrotic response and proliferation of connective tissue. -Furthermore, it disturbs the balance between matrix metalloproteinases and the naturally occurring inhibitor, leading to matrix breakdown and replacement by connective tissue-secreted matrix. -The fibrous tissue bands (septa) separate hepatocyte nodules, which eventually replace the entire liver architecture, leading to decreased blood flow throughout. -The spleen becomes congested, which leads to hypersplenism and increased sequestration of platelets. – -Portal hypertension is responsible for most severe complications of cirrhosis.
Clinical Features of Hepatic Cirrhosis -May be clinically salient (asymptomatic) -Non-specific manifestations: anorexia; weight loss; weakness; abdominal gaseousness; digestive complaints … -Hepatomegaly hard, irregular & painless. -Hepatic atrophy disease progression -Jaundice
Clinical Features cont… -Ascites.Circulatory changes spider telangiectasia; palmer erythema; cyanosis.Endocrine changes -loss of libido -hair loss -men: gynaecomastia, testicular atrophy, impotence -woman: breast atrophy, irregular menses, amenorrhea
ASCITES
Clinical Features cont… -Hemorrhagic tendency Bruises; purpura; epistaxis; menorrhagia -Portal hypertension Splenomegaly, collateral vessels, variceal bleeding -Fetor hepaticus -Hepatic encephalopathy -Other Features pigmentation; digital clubbing; low grade fever
PORTAL HYPERTENSION MANIFESTATION -Portal hypertension is defined as a sustained elevation of pressure in the portal vein above the normal level. -The primary mechanism for inducing portal hypertension, regardless of the disease, is increased resistance to blood flow through the liver. Increase in splanchnic arterial flow.- -Decreased outflow through the hepatic vein and increase inflow combine to overload the portal circuit. -The back pressure in the portal system causes splenomegaly and is partly responsible for the accumulation of ascites.
PORTAL HYPERTENSION MANIFESTATION -The important collateral channels which develop as a result of cirrhosis and portal hypertension are found in lower esophagus, the shunting of the blood through this circuit to venae cavae cause dilatation of these veins (esophageal varices) -Collateral circulation also involves the superficial to dilated veins around the umbilicus (caput medusa) -Dilatation of anastomosis between the branches of the inferior mesenteric vein and rectal vein lead to develop of internal hemorrhoids
Caput Madusae
Esophageal Varices
DIAGNOSIS -Routine lab tests may be normal - prothrombin time - serum albumin - serum globulin - ALT/AST -ALP normal or -Bilirubin usually normal -Anemia common -Hypersplenism leucopoenia & thrombocytopenia -Ultrasound textual abnormalities; confirm hepatosplenomegaly -CT liver size, texture & density -Endoscopy esophageal varices
Prognosis & Treatment -Prognosis difficult to estimate -Complications poor prognosis -Supportive treatment withdrawal from toxic agents attention to nutrition, treatment of complications -Specific therapies altering the collagen production are being evaluated -Advanced liver cirrhosis transplantation