Sinusoids of liver are delicate structure and their walls are composed of endothelium. Sinusoids blockage can cause dilatation of these structures, liver can become engorged with blood cell. Microcystin, beryllium, dimethyl nitrosamines, and some anticancer drugs.

Scarring process in response to liver injury Liver repair injury through the deposition of new collagen. Hepatic stellate cell (ito cell) (HSC) produce matrix. Fibrosis is not only the result of necrosis. Derangements in the synthesis and degradation of matrix by injured mesenchymal cell.

Cellular mechanism of liver fibrosis

Liver matrix produced by hepatocytes, lipocytes Fibroblast, myofiberoblast, space Disse Necrotic cell Inflammatory cell Cytokines Cytokines stimulate matrix producing cells Repeated and persistent injury develop fibrosis Overcome the degrading ability of matrix on the part of liver that attempts to eliminate those formation through degrading enzymes which are produced by fibroblasts, neutophils.

A: Liver showing periportal fibrosis and cholestasis B: Portal tract showing ductal metaplasia and periportal fibrosis C: Portal - portal bridging fibrosis D: Portal - portal bridging fibrosis

 Cirrhosis of liver is fibrotic disease.  Loss of significant hepatic function.  Organ failure.  Characterized by accumulation of fibrous tissues and lipids.  Portal hypertension  General cardiovascular compromise.  A diet poor in protein and vitamin B increases the progression of the disease  Ethanol, aflatoxin B, vinyl chloride, arsenic.

Cholestatic cirrhosis in extrahepatic biliary tract atresia

 Hepatic carcinogens, aflatoxinB, safrole, CCl4,alkylnitrosamines,acetylaminofluorene  Vinyl chloride, arsenic (Angiosarcoma)  Malignant neoplasm linked chemical exposure.  Cirrhosis is predisposing factor of hepatic cancer.  Hepatic sinusoids, hepatocytes, bile duct.

 Measurements of total protein  Albumin and globulin  Prothrombin time  Bilirubin  various liver enzymes  ALT (alanine aminotransferase or SGPT)  AST (aspartate aminotransferase or SGOT)  GGT (gamma-glutamyltranspeptidase)  ALP (alkaline phosphatase)

Total protein 1) serum total protein6.5 to 8.2 grams/ deciliter. Globulins 1) Liver cells and the immune system. Albumin 1) If the liver is badly damaged, it can no longer produce albumin. 2) Maintains the amount of blood in the veins and arteries. 3) Low albumin levels: causing swelling in the feet and ankles. 4) The normal albumin range is from 3.9 g/dl to 5.0 g/dl.

Prothrombin 1) Factor II 2) Prothrombin is made in the liver. 3) The normal time needed for blood to clot is between 10 and 15 seconds. 4) A longer prothrombin time can be caused by serious liver disease or:  A lack of vitamin K,  Blood-thinning medicines,  Other medications that can interfere with the test.  Certain bleeding disorders.

ALT An increase in ALT levels may be due to:  Acute pancreatitis  Celiac disease  Cirrhosis Cirrhosis  Death of liver tissue (liver necrosis)  Hepatitis (viral, autoimmune) Hepatitis  Hereditary hemochromatosishemochromatosis  Infectious mononucleosis  Lack of blood flow to the liver (liver ischemia)  The normal range of ALT levels is between 5 IU/L to 60 IU/L.

AST  Other organs besides the liver.  High AST levels sign of liver trouble.  The normal range for AST levels in the bloodstream are 5 IU/L to 43 IU/L.

GGT and ALP ALP metabolizes phosphorus and brings energy to the body. GGT brings oxygen to tissues. If the bile duct is inflamed or damaged, GGT and ALP can get backed up and spill out from the liver into the bloodstream. Causes of elevated ALP and GGT levels include:  Scarring of the bile ducts (called primary biliary cirrhosis)  Fatty liver (steatosis)  Alcoholic liver disease  Liver inflammation from medications and certain herbs  Liver tumors  Gallstones or gall bladder problems  The normal range of ALP is from 30 IU/L to 115 IU/L.  The normal range of GGT is from 5 IU/L to 80 IU/L.

 Bilirubin can leak out from the liver into the bloodstream if the liver is damaged.  When bilirubin builds up, it can cause jaundice - a yellowing of the eyes and skin, dark urine and light colored feces. The causes of abnormal bilirubin levels include:  Viral hepatitis,  Blocked bile ducts,  Other liver diseases,  Liver scarring (cirrhosis)  Normal total bilirubin levels range from 0.20mg/dl to 1.50mg/dl.  Direct bilirubin testing measures bilirubin made in the liver.  The normal level of direct bilirubin range from 0.00mg/dl to.03 mg/dl