Hepatobiliary System General Medicine

Hepatobiliary System

Functions Of Liver:

Question 1. Enumerate important functions of liver.
Answer:

Important functions of liver are listed:

Important functions of liver:

• Protein metabolism and urea formation
• Carbohydrate metabolism: Includes gluconeogenesis, glycogenolysis, and glycogenesis
• Lipid metabolism
• Bilirubin formation from hemoglobin degradation
• Metabolism of vitamins and minerals

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• Hormone metabolism
• Drug and alcohol metabolism
• Cholesterol metabolism
• Bile acid formation and bile secretion
• Synthesis of plasma proteins including coagulation factors
• Immunological function: Removal of gut endotoxins and foreign antigens
• Maintains core body temperature
• Maintains pH balance and correction of lactic acidosis

Liver Function Tests:

Question 2. Discuss the liver function tests. Discuss approach to jaundice.
Answer:

Liver Biochemistry:

No single test alone can be used to assess liver function.

Serum Bilirubin:

• Normal values of total serum bilirubin are between 0.3 and 3 mg/dL, with 95% of a normal population falling between 0.2 and 0.9 mg/dL (almost all unconjugated). Bilirubin is a degradation product of hemoglobin and hem-containing proteins. Bilirubin metabolism is summarized.
• Total serum bilirubin = Conjugated (direct) + unconjugated (indirect) bilirubin.

Question 3. Write short answer on causes/diseases with elevated/very high serum alkaline phosphatase.
Answer:

Alkaline phosphatase:

• Many distinct isoenzymes — liver, bone, kidney, placenta, small intestine, origin can be determined by electrophoretic separation.
• Normal serum level: 3–13 KA units (80–240 IU/L).
• Raised levels of liver-derived ALP are not totally specific for cholestasis.
• Low levels: Wilson’s disease, with fulminant hepatitis and hemolysis, possibly because of reduced activity of the enzyme owing to displacement of the cofactor zinc by copper. Ratio of ALP to total bilirubin of <2 is quite specific for Wilson’s disease.
• Raised serum ALP levels:
• <5 times: Hepatocellular jaundice
• >4 times:
• Obstructive jaundice (intrahepatic or extrahepatic obstruction)
• Infiltrative liver diseases, e.g., cancer, metastases, and amyloidosis
• Bone lesions with rapid bone turnover, e.g., Paget’s disease
• Primary biliary cirrhosis

ϒ-glutamyl transpeptidase (GGT):

• Microsomal enzyme is present in liver, renal tubules, pancreas, and intestine.
• Identify the source of isolated elevation in serum ALP (GGTP is normal in bone disease)
• Screening test for alcoholism: If ALP is normal, raised serum γ-GT is a good guide to alcohol intake of more than 60 g/day. (Detection of alcohol abuse in patients who deny it).
• Elevated GGT levels:
• Biliary obstruction
• Alcoholism
• Liver parenchymal damage
• Nonalcoholic fatty liver
• Other causes: Chronic obstructive lung disease, diabetes mellitus, hyperthyroidism, obesity, and renal failure.
• Patients taking phenytoin, barbiturates, and antiretroviral therapy — nonnucleoside reverse transcriptase inhibitors and abacavir

5-nucleotidase:

• Microsomal enzyme has similar significance as that of GGT.
• 5′NT levels are not increased in bone disease but are increased in hepatobiliary disease.

Lactate dehydrogenase (LDH): Not useful in diagnosis of liver diseases

• Moderate elevations: Ischemic hepatitis and hepatic metastasis.
• ALT/LDH ratio >5 suggests ischemic hepatitis while ratio <5 is seen with paracetamol toxicity.

Biosynthetic Function of the Liver:

Causes of prolonged prothrombin time:

• Severe liver damage: Acute hepatitis (e.g., viral hepatitis), cirrhosis
• Deficiency of vitamin K
• Obstructive jaundice that reduces vitamin K absorption
• Fat malabsorption
• Poor intake
• Antibiotic therapy which produces destruction of vitamin
• Producing commensals
• Disseminated intravascular coagulation
• Drugs and toxins: Warfarin, rivaroxaban, apixaban, edoxaban, dabigatran, viper envenomation, anticoagulant rodenticide poisoning

Ceruloplasmin:

• It is an acute-phase reactant synthesized by the liver.
• In blood, it binds to copper and acts as a major carrier for copper.
• Normal plasma level: 20–60 mg/dL
• Causes of elevated levels: Infections, liver diseases, obstructive jaundice, rheumatoid arthritis, and pregnancy.
• Causes of decreased levels: Wilson’s disease (due to decreased rate of synthesis), neonates, Menkes disease, kwashiorkor, marasmus, protein-losing enteropathy, and copper deficiency.

Cholesterol:

• It is synthesized in the liver. Advanced liver disease may be associated with very low cholesterol. However, primary biliary cholangitis (PBC) may be associated with markedly raised cholesterol. Similarly, a low urea level also indicates severe liver dysfunction. Liver functions tests and their significance are summarized.