JAUNDICE
الدكتور خلدون ذنون- كلية طب نينوىالمرحله الرابعة
Objectives
The following facts need to be digested:
Bilirubin metabolism
liver functions tests
Types of jaundice
Prognosis of jaundice ranges from excellent to fatal.
Introduction
Yellow appearance of the skin, sclera & mucous membranes due to increased bilirubin level in the body fluids.Detectable clinically when plasma bilirubin > 3mg/dl (50(mol/L).
Bilirubin does not cross the blood brain barrier except in neonatal period.
Sources of unconjugated bilirubin
Haemoglobin breakdown.
Catabolism of other haem-containing proteins e.g myoglobin & cytochrome enzymes.
Ineffective erythropoiesis.
Bilirubin metabolism
Unconjugated bilibrubin 250-300mg/day from haem is conjugated by liver glucuronyl transferase ( mono- or diglucuronide which is excreted through bile ( large intestine, colonic bacteria ( stercobilinogen 100-200mg/day ( stercobilin ( stool.
Small amount of stercobilinogen ( blood as urobilinogen ( entero- hepatic circulation) or reach the kidneys & excreted as urobilinogen 4mg /day & becomes urobilin in urine.
Bilirubin in the blood is mainly unconjugated; it is not water soluble, bound to albumin & does not pass into the urine.
Conjugated bilirubin is water-soluble & is lost with the stool or excreted via kidneys into the urine.
Mechanisms producing jaundice
A- Increased production of bilirubin (heamolytic).B- Impaired excretion of bilirubin:
1. Hepatocellular jaundice (acute &chronic parenchymal liver disease)
2. Cholestatic jaundice .
3. Congenital hyperbilirubinaemia: (Gilbert, Crigler-Najjar I & II,
Dubin-johnson, Rotor) syndromes.
HAEMOLYTIC JAUNDICE
Due to increased destruction of RBC or their precursors in the marrow causing excess bilirubin production.Jaundice is usually mild as normal liver can excrete 6 times bilirubin load greater than normal except in the newborn or liver disease .
Clinical features
Mild jaundice.Normal-coloured or dark stool due to excess stercobilinogen.
Urine turns dark on standing as excess urobilinogen excreted in urine changes to urobilin.
Palor, anaemia, splenomegaly.
Investigation
Plasma bilirubin usually < 100 (mol/L < 6mg/dl.
Liver function tests are normal.
There is no bilirubin in urine because excess plasma bilirubin is mainly unconjugated.
Evidence of haemolytic anaemia i.e ( HB, reticulocytosis, and macrocytosis, target RBC, active bone marrow.
Treatment: Treat the cause & the anaemia itself.
HEPATOCELLULAR JAUNDICE
Parenchymal liver disease leads to inability of the liver to transport bilirubin into bile.
Hepatocytes have impaired uptake & transport of unconjugated bilirubin into the biliary canaliculi.
Swelling of the cells & oedema result in obstruction of the biliary canaliculi with biliary stasis.
Both conjugated & unconjugated bilirubin ( in the blood.
AST & ALT are mainly increased with lesser increase in ALP & GTT.
Liver biopsy has a role in defining the cause.
OBSTRUCTIVE(CHOLESTATIC) JAUNDICE
Conjugated B. is unable to enter the bile canaliculi & passes back into the blood.Failure of clearance of unconjugated B. arriving at the liver cells.
Aetiology
A- Intrahepatic ( medical ) : viral hepatitis , autoimmune hepatitis , drugs , alcohol , pregnancy , post operative , severe bacterial infections , Hodgkins lymphoma , primary biliary cirrhosis , primary sclerosing cholangitis , idiopathic recurrent cholestasis .B- Extrahepatic (surgical)
Choledocholithiasis.
Carcinoma: ampullary, pancreatic, bile duct, secondary.
Cystic fibrosis, parasitic infection, traumatic biliary stricture.
Clinical features
A- Cholestasis: early: jaundice may be deep yellow to green, dark urine, pale stools, and pruritis.Late features: xanthelasma, xanthoma, malabsorption (weight loss, steatorrhea, osteomalacia, bleeding).
B- cholangitis: fever, rigor, right hypochondrial pain, hepatic abscess.
C- Features of underlying disease:
Static or increasing jaundice: carcinoma.
Fluctuating jaundice: stone, stricture, pancreatitis, choledochal cyst.
Abdominal pain: stone, pancreatitis, choledochal cyst.
Cholangitis: stone, stricture, choledochal cyst.
Abdominal scar: stone, stricture.
Irregular hepatomegaly: hepatic carcinoma.
Palpable gall bladder: carcinoma below cystic duct e.g pancreas.
Abdominal mass: carcinoma, pancreatic cyst, choledochal cyst.
Occult blood in the stool: papillary tumor.
Investigations
(( Bilirubin in the blood mainly conjugated.(( Alkaline phosphates & GGT.
Small ( in aminotransferases.
(( Bilirubin in urine.
U/S: may show liver shape &size, biliary dilatation, gall stones, gall bladder dilatation, tumors.
Investigation of the cause : U/S , CT , MRCP , ERCP , PTC , liver biopsy , laparoscopy , laparatomy .
( PT: vitamin K deficiency.( S. calcium: vitamin D deficiency.
CONGENITAL NON-HAEMOLYTIC HYPPERBILIRUBINAEMIA
GILBERTS SYNDROME
Most common form, all other forms are very rare.Autosomal dominant.
Due to ( glucuronyl transferase & ( bilirubin uptake.
jaundice is mild due to excess unconjugated B. in the blood < 100 (mol/L
During fasting the level of unconjugated B. increases.
Phenobarbital decreases the level of unconjugated B.
Liver function tests & liver histology is normal.
No treatment, excellent prognosis.
Important because it may be mistaken with more serious liver diseases.
CRIGLER-NAJJAR TYPE I
Autosomal recessive.Absent glucuronyl transferase.
Kernicterus in neonate & rapid death .
CRIGLER-NAJJAR TYPE II
Autosomal dominant.(( Glucuronyl transferase ( (( unconjugated B.
Presents in neonate.
Treatment: UV light, liver transplant.
DUBIN-JOHNSON SYNDROME
Autosomal recessive
( Canalicular excretion of bilirubin.
( Conjugated bilirubin in the blood.
Mild disease, no treatment is needed.
ROTORS SYNDROME
Autosomal dominant.( Bilirubin uptake, ( intrahepatic binding.
( Conjugated bilirubin in the blood.
Mild disease, no treatment is needed.
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