CLINICAL CHEMISTRY 2 MLT 302 LIVER FUNCTION AND

CLINICAL CHEMISTRY 2 (MLT 302) LIVER FUNCTION AND THE BILIARY TRACT LECTURE FIVE Dr. Essam H. Aljiffri 1

LIVER DISEASES Acute Viral Hepatitis • Hepatitis occurs as a complication of many viral infections, the term viral hepatitis usually refers to three types of infection (A, B and C). • Hepatitis A is transmitted by the oro faecal route while; Ø hepatitis B and C are transmitted by blood products or other body fluids. • Attacks vary in severity and may be asymptomatic with only a transient rise in transaminases. 2

Acute Viral Hepatitis • The basic pathology of these infections is similar; Ø acute inflammation, and Ø hepatic necrosis occurs. • Symptoms are often non specific at presentation, including; Ø Anorexia, and Ø Nausea. 3

Acute Viral Hepatitis • Serum transaminases may be elevated significantly, sometimes exceeding 20 times the upper limit of normal. • Serum transaminase activities usually peak before the onset of jaundice which occurs typically 34 days following the onset of symptoms, • the urine often becoming dark and the feces pale. 4

Acute Viral Hepatitis • Impaired excretion of bilirubin from hepatocytes is often the major cause of hyperbilirubinaemia which is therefore mainly conjugated. 5

Acute Viral Hepatitis • Bilirubinuria is common. • Modest increases in alkaline phosphatase greater than three times the upper limit of normal. 6

Chronic Hepatitis • Chronic persistent hepatitis may follow acute viral hepatitis. • Transaminase activities often being abnormal biochemical finding. 7

Chronic Hepatitis • Chronic active hepatitis may result from persisting: Ø Ø Ø 8 hepatitis B infection, other viral infections, auto immune hepatitis, drug reactions, alpha 1 antitrypsin deficiency, alcohol abuse.

Chronic Hepatitis • Jaundice with very high serum transaminase activities is common; Ø immunoglobulin levels are often high. • Serum albumin concentrations may fall as the disease progresses. 9

Hepatic Cirrhosis • Cirrhosis is a diffuse process in which fibrosis and nodule formation follows: Ø hepatocellular necrosis. • There are many causes: 10

Causes of liver cirrhosis • Chronic alcohol abuse • Viral hepatitis • Inherited metabolic disorders Ø Haemochromatosis Ø Wilson’s disease Ø Galactosaemia Ø α Antitrypsin deficiency Ø Tyrosinaemia Ø Type IV glycogen storage disease • Prolonged cholestasis • Hepatic venous outflow obstruction Ø Heart failure • Toxins, drugs 11

Hepatic Cirrhosis • The normal architecture of the liver is disrupted in cirrhosis, with changes in the blood supply resulting in portal hypertension. • Slight increases in transaminases, particularly AST and GGT, are the commonest abnormalities 12

Hepatic Cirrhosis • Jaundice is accompanied by increased urobilinogen and bilirubin excretion in urine. • Increases in serum immunoglobulins may occur. • Patients with cirrhosis are at increased risk of developing: Ø hepatocellular carcinoma, indicated by ( high alpha fetoprotein concentrations in serum). 13

Hepatocellular and Acute (Fulminant) Hepatic Failure • Hepatocellular failure may result from almost all causes of liver disease including: Ø viral hepatitis, Ø cirrhosis, Ø drug overdoses, e. g. paracetamol, and • prolonged cholestasis. • Jaundice is often progressive and transaminases are usually raised. 14

Hepatocellular and Acute (Fulminant) Hepatic Failure • Changes in nitrogen metabolism occur, including: Ø reduced urea synthesis and Ø Blood levels of ammonia may rise. • Hypoglycaemia may occur owing to impaired gluconeogenesis. • Abnormalities in oestrogen androgen metabolism occur and a degree of feminization is common in male patients. 15

Hepatocellular and Acute (Fulminant) Hepatic Failure • Testicular atrophy is common, with reduced testosterone level, particularly in: Ø alcoholic patients. • Fulminant hepatic failure is caused by: Ø sudden massive necrosis, or Ø severe impairment of liver function. 16

Hepatic Malignancy • The liver is a common site for secondary carcinoma. • Increases in serum alkaline phosphatase and GGT due to: Ø tumours causing cholestasis in parts of the liver are common abnormalities of liver function tests. 17

Toxic Liver Damage • Liver injury may follow exposure to a number of: Ø pharmacological, or Ø chemical agents. • With some, toxic effects are predictable and dose related. 18

Gallstones • Most gallstones, unlike renal stones, do not contain calcium and are: • radiotranslucent. • The main constituent of gallstones in Western countries is cholesterol. - Cholesterol gallstone formation due to: Ø supersaturation of the bile with cholesterol. 19