Required Knowledge base to manage patients
with Jaundice
Dr A.J. Chandrasekhar
Biochemical definition of jaundice
Bilirubin >2.5 mg/dl
Bilirubin metabolism
Red cell phase (Source)
- 80% of bilirubin is derived from RBC's
- When red cells die, the heme moiety gets oxidized to biliverdin,
which is then metabolized to bilirubin.
- This unconjugated bilirubin is tightly bound to albumin.
- Unconjugated bilirubin can cross blood brain barrier and can
cause encephalopathy
- Blue light changes unconjugated bilirubin water soluble and
can be excreted without conjugation.
- Neonatal brain cells , especially basal ganglia have an
affinity for unconjugated bilirubin
Role of Liver
Liver has a central role in metabolism of
- bilirubin uptake.
-
conjugation
- excretion into bile
Bilirubin uptake
Conjugation
- Bilirubin glucuronosyl transferace catalyzes and conjugates
bilirubin to glucuronic acid generating bilirubin glucuronide.
- Conjugated bilirubin is bound to albumin in two forms
- Reversible similar to unconjugated bilirubin
- Long standing period results in irreversible complex with
albumin (biliprotein). this is not excreted by kidney and can stay in serum for
weeks even after relief of obstruction. They disappear with normal degradation
of albumin.
- Conjugated bilirubin is water soluble and is excreted in
urine.
- Presence of bilirubin in urine is indicative of conjugated
hyperbilirubinemia.
Excretory phase
- Excretion is the rate limiting step
- After secretion in bile, bilirubin is transported through the
biliary tract into duodenum.
GI phase
- Bilirubin is either excreted in feces or converted into
urobilinogen by ileal or colonic bacteria.
- Urobilinogen gets absorbed from ileum
and colon into portal circulation.
- Some taken up by liver and re-excreted in
bile.
- Rest bypasses liver and excreted by kidney.
How do you Classify jaundice
By metabolic mechanisms |
By Pathological mechanism |
Overproduction |
Hemolytic jaundice |
Decreased hepatic uptake |
Hepatocelluar failure?? |
Decreased hepatic conjugation |
Hepatocelluar failure?? |
Decreased excretion into bile |
Cholestatic jaundice
Obstructive jaundice |
Unconjugated hyperbilirubinemia
80-85 % of unconjugated bilirubin (indirect) in
unconjugated hyperbilirubinemia
- Increased bilrubin production
- Decreased hepatic uptake/Decreased glucoronide conjugation
- Gilbert's syndrome
- Drugs
- Physiologic jaundice of newborn
Conjugated hyperbilirubinemia
>50% direct reacting indicates conjugated
hyperbilirubinemia
- Hereditary disorder
- Hepatocelluar disease
- Viral hepatitis
- Alcoholic hepatitis/Cirrhosis
- Ischemia/CHF
- Autoimmune hepatitis
- Metabolic: Rye syndrome, Wilson's disease
- Cholestatic jaundice
- Intrahepatic
- Granulomatous infection
- Severe inflammation
- Malignancy
- Primary biliary cirrhosis
- Drugs
- Extrahepatic
- Choledocholithiasis
- Primary sclerosing cholangitis
- Pancreatitis
- Pancreatic carcinoma
Important historical information you should
gather from history and why
- Duration long standing
- Nausea, vomiting, anorexia. / Hepatitis
- Asymptomatic / Obstructive Jaundice, Cancer Pancreas
- Abdominal pain / Cholecystitis, Cholangitis, Hepatitis,
Cancer
- Fever/ Cholecystitis, Cholangitis, Hepatitis
- Weight loss / Cancer, Cholangitis
- Bowel habits
- Blood transfusion / Hepatitis
- Drug abuse / Hepatitis
- Ethanol / Fatty liver, Alcoholic hepatitis, Cirrhosis,
Pancreatitis
- Medications INH, chlorpromazine, anabolic steroids,
acetaminophen
- Travel / Hepatitis
- Pruritus. / Bile salts get deposited in tissue and lead to itching.
Obstructive jaundice.
- Acholic stools / Obstructive jaundice
- Biliary surgery / Stones, Cholangitis
- Pregnancy
- Inflammatory bowel disease / Cholangitis
- Surgery / Post-op jaundice
- Prior or concurrent malignancy / Liver metastases
- History of hemolytic anemia / Sickle cell, Thalasemia
Important physical findings you should gather
from physical examination and why
- Jaundice.
- Jaundice results from accumulation of bilirubin. Imbalance between production and clearance.
- Jaundice detectable, when the bilirubin is about twice the normal
range (2-2.5 mg/dl)
- Scleral tissue is rich in elastin, which has a high affinity
for bilirubin
- Darkening of urine and scleral icterus precede yellowing of
skin
- Other causes of yellow skin carotenemia. carotenemia does not cause scleral icterus
- Hyperbilirubinemia per se has no patho-physiologic effect.
- Bilirubin is present in body fluids in proportion to their
albumin content. Not present in true secretions like tears, saliva and pancreatic
juice.
- Influenced by blood flow and edema. paralyzed extremities and
edematous areas tend to remain uncolored
- Greenish hue/long standing problem. /Long standing jaundice assumes a greenish hue due to oxidation
of circulating bilirubin to biliverdin
- Fever/biliary tract inflammation
- RUQ tenderness/biliary tract inflammation
- Enlarged tender liver/hepatic inflammation, malignancy
- Palpable gall bladder/distal biliary obstruction from
malignancy
- Splenomegly/Portal hypertension
- Hyperestrogen state/ Cirrhosis
- Gynaecomastia
- Testicular atrophy
- Spider angiomata
- Palmar erythema/ Cirrhosis
- Facial telengiectasia/ Cirrhosis
- Dupuytren's contracture/ Cirrhosis
- Wasting/ malignancy, biliary disease
- Scratch marks / Obstructive jaundice. Itching due to bile
salt deposition.
- Adenopathy/ cancer, lymphoma
- Masses/ cancer
- Xanthomata/ Primary biliary Cirrhosis
- Kayser-fleischer rings/ Wilson's disease
Useful lab studies in evaluation of a patient
with jaundice and their utility
- Urine bilirubin. / Presence of bilirubin in urine is indicative of conjugated
hyperbilirubinemia.
- Urine urobilinogen
- Serum bilirubin total, direct and indirect
- Normal serum bilirubin 0.3-1.0 mg/dl
- 90% of normal bilirubin is in unconjugated form bound to
albumin (indirect). Not excreted in urine.
- Bile salts enhance renal excretion of bilirubin, explaining
why bilirubin level plateaus around 40 mg/dl in obstructive jaundice.
- Higher levels occur with hepato-celluar injury.
- Liver enzyme
- Alkaline phosphatase
- Serological viral studies A, B, C, D, E, CMV.
- Liver biopsy
- CT
- Ultrasound
- MRI
- Doppler flow
- Endoscopic cholangiography
- PTC ( percutaneous transhepatic cholangiography)
- ERCP (endoscopic retrograde cholangiopancretography) /cytology/biopsy
Chronic bile stasis
- Pruritus - bile salts
- Steatorrhea - malabsorption
- Fat soluble vitamin deficiency (K, A, D)
- Elevated cholesterol - xanthomas
- Progressive Jaundice
- Gallstones
- Biliary cirrhosis
- Hepatocellular carcinoma