Vascular injury

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.

Vascular injury

Liver fibrosis

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.

Changes in the hepatic architecture associated with advanced hepatic fibrosis

Cellular mechanism of liver fibrosis

Matrix production& degradation

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.

Central fibrosis (mild/sever)

Portal and periportal fibrosis

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

Biliary fibrosis

Chronic viral hepatitis

Cirrhosis 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.

Liver cirrhosis

Alcohol induced cirrhosis

Cholestatic cirrhosis

Cholestatic cirrhosis in extrahepatic biliary tract atresia

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Biliary cirrhosis

Biliary cirrhosis

Cirrhosis tyrosinema

Tumors of liver

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.

Hepatocellular carcinoma

Hepatocellular carcinoma

CT scan of hepatocellular carcinoma

Ultra sonography of hepatocellular carcinoma

LFTs (liver function tests) 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)

Measuring Liver Proteins

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.

Measuring Liver Proteins

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.

Measuring Liver Enzymes ALTAn increase in ALT levels may be due to: Acute pancreatitis Celiac disease Cirrhosis Death of liver tissue (liver necrosis) Hepatitis (viral, autoimmune) Hereditary hemochromatosis 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.

Measuring Liver Enzymes

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.

Cholestatic Liver Enzymes 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

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