JAUNDICE
A lecture for third year students (Dr. Ismael D.)Jaundice: is yellowish discoloration of the skin, sclera and mucous membrane, resulting from an increased bilirubin concentration in the body fluid. It is usually detectable clinically when the plasma bilirubin exceeds 50mol/l (~3mg/dl)
Bilirubin metabolism
About 250mg of unconjugated bilirubin is produced from the catabolism of Haem every day. Bilirubin in the blood is almost all unconjugated and, because it is not water soluble, it is bound to albumin and does not pass into the urine. Unconjugated bilirubin is conjugated by the glucuronyl transferase into mono and diglucuronide bilirubin. These are water soluble and by specific carriers enter the bile and reach intestine.Conjugated bilirubin is metabolized by colonic bacteria to form stercobilinogen which may be oxidized to stercobilin and both are excreted in the stool. A small amount of stercobilinogen (4mg/day) is absorbed from the bowel and go to the blood and excreted through the kidney (colorless urobilinogen).
Clinical types of Jaundice:
Haemolytic anaemia: Increased destruction of RBCs or their precursors in the marrow, causing increasing production of bilirubin.Jaundice is usually mild (> 100mol/l) as healthy liver can excrete bilirubin six times greater than normal before unconjugated bilirubin accumulates in the plasma. This is not applied to new born (Kernicterus may occur).
There are no stigmata of chronic liver disease other than jaundice.
Normal or dark colored stool (stercobilinogen). Also urine may turn dark on standing as urobilin is formed.
Pallor due to anaemia and splenomegaly are usually present.
Liver function tests (LFTs) are normal.
No bilirubinuria.
Blood count and film may show evidence of haemolytic anaemia
2. Congenital non-haemolytic hyperbilirubinaemia:
Are inherited either as autosomal dominant like Gilbert and Rotors disaeses or autosomal recessive like Dobin Johnson and type 1 Crigler-Najar.
Gilbert Disease: This is the comments type and benign condition causes mild unconjugated hyperbilirubinaemia due to decrease in the level of glucuronyl transferase or decrease bilirubin uptake inherited as (AD). Usually follows viral infection or fasting well respond to phenobarbital.
3. Hepatocellular jaundice: result from inability of liver to transport bilirubin into the bile as a result of parenchymal liver disease. Swelling and oedema of cells may cause obstruction to the biliary canaliculi. Both conj. And unconj. Bilirubin are increased.
Causes: Viral hepatitis, drugs, alcohol,.
The severity of jaundice, the other clinical features, investigation , treatment, and prognosis vary with underlying causes.
4. Cholestatic jaundice: Tend to become progressive and severe because conjugated bilirubin is unable to enter the bile canaliculi and passes back into the blood and because failure of clearence of unconjugated bilirubin arriving at the liver cells.
Causes of obstructive jaundice
A. Intrahepatic cholestasis stage of the following conditions:Primary biliary cirrhosis, autoimmune H.
Primary sclerosing cholangitis.
Alcohol, pregnancy, BRIC
Drugs, hogdkin lymphoma.
Viral hepatitis, cystic fibrosis, severe bacterial infection, post-operative
B. Extrahepatic:
Choledocholithiasis.
Carcinoma (ampullary, pancreatic,bileduct).
Parasitic infection.
Traumatic biliary stricture.
Clinical features in cholestatic jaundice
Early features:Jaundice
Dark urine
Pale stool
Pruritis
2. Late features:
Xanthelasma and xanthomas
Malabsorption (weight loss, steatorrhea, osteomalacia, bleeding tendency)
3. Features of choleangitis:
Fever
Rigor
Pain
Early Investigations of obstructive jaundice
The history and clinical exam. determine the investigation in individual patients.Usually biochemistry tests show greater elevation of the alkaline phosphatase and GGt compared with aminotransferases (ALT, AST).
Ultrasound is performed to identify any biliary dilatation.
Subsequent investigation is shown in next Schema.
Clinical features suggesting an underlying cause of obstructive jaundice
Progressive, static or flacuating jaundic(carcinoma, stone, stricture, pancreatitis).
2. Abdominal pain: (stone, pancreatitis, choedochal cyst).
3. Irregular hepatomegaly: (hepatic ca.)
4. Palpable gallbladder: (ca. below custic duct (usually pancreas)
5. Abdominal mass: (Ca, Pancreatic cyst, choledochal cyst)
6. Occult blood: Papillary tumour