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Liver Cirrhosis

Dr.F.Bennani

DEFINITION OF CIRRHOSIS

Cirrhosis
End stage of any chronic liver disease. Characterized histologically by regenerative nodules surrounded by diffuse fibrous tissue

Note : Focal fibrosis in the liver is not cirrhosis e.g : healing of liver abcess

Chronic Liver Disease


Liver Injury

Inflammation
Fibrosis & Hepatocyte regeneration

Cirrhosis

Causes
Alcoholic liver disease Viral hepatitis Primary biliary cirrhosis Haemochromatosis others

Pathogenesis
Liver damage Replacement by fibrous tissue (fibrosis)

No fibrous tissue in normal liver What type of cells responsible for fibrosis

Fibrosis
Key event in Fibrosis is Stellate cell activation
In Normal Liver Stellate Cells store Vitamin A Activation leads to:
Loss of Vitamin A Proliferation Differentiation myofibroblasts Fibrogenic

Stellate Cell Activation

Fibrosis
Activated HSC
Protein synthesis Collagen synthesis

Formation of Extracellular Matrix (ECM)


Collagens (Type I & III) Glycoproteins e.g. laminin, fibronectin Proteoglycans e.g. dermatin, chondroitin sulphate

ECM deposition fibrotic scar

Combination of fibrosis & Hepatocyte regeneration Cirrhosis

HISTOLOGICAL IMAGE OF A NORMAL AND A CIRRHOTIC LIVER

Normal

Cirrhosis

Nodules surrounded by fibrous tissue

GROSS IMAGE OF A NORMAL AND A CIRRHOTIC LIVER

Normal

Cirrhosis
Irregular surface

Nodules

Consequences of Cirrhosis
Impaired catabolic activity
breakdown of by-products of metabolism
E.g. conjugation & excretion of bilirubin jaundice

Impaired synthetic activity


synthesis of molecules especially proteins necessary for normal function
E.g. clotting factor production coagulopathy

Disruption of microvasculature

Portal Hypertension

Ascites- Mechanism of formation


Portal Hypertension
Renin-Angiotensin Activation Renal Dysfunction

Antidiuretic Hormone

Sodium and water retention

Ascites

Complications of cirrhosis
A.Portal hypertension: a.esophageal varices b.ascitis. c.splenomegaly B.Hypoproteinemia: a.coagulopathy --- bleeding b.hypoalbuminemia --- oedema c.low serum globulin ----- low immunity infection C.Hepatic encephalopathy :impaired metabolism of ammonia D.Hepatocellular carcinoma ( hepatoma ) high level of alpha-fetoprotein