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jaundice (icterus)
Etiology:
1) elevated unconjugated bilirubin
a) increased bilirubin production
- extravascular hemolysis
- extravasation of blood into tissues
- intravascular hemolysis
- dyserythropoiesis
b) impaired hepatic bilirubin uptake
- congestive heart failure
- porto-systemic shunt
- Gilbert's syndrome (some)
- pharmaceutical agents
- rifampin
- probenecid
c) impaired bilirubin conjugation
- Crigler-Najjar syndrome type-1 & type-2
- Gilbert's syndrome
- neonates
- hyperthyroidism
- ethinyl estradiol
- liver disease
- chronic persistent hepatitis
- advanced cirrhosis
- Wilson's disease
2) elevated conjugated bilirubin
a) biliary obstruction (extrahepatic cholestasis)
- choledocholithiasis
- tumors, extrinsic & intrinsic
- cholangiocarcinoma
- pancreatic carcinoma
- periampullary carcinoma
- metastatic carcinoma
- primary sclerosing cholangitis
- AIDS cholangiopathy
- cytomegalovirus (CMV)
- cryptosporidium
- HIV
- acute pancreatitis, chronic pancreatitis
- strictures after invasive procedures
- parasitic infections
- Ascaris lumbricoides
- liver flukes
- sphincter of Oddi dysfunction
- histiocytosis X
- Mirizzi's syndrome
- periampullary diverticulum
b) intrahepatic cholestasis
- viral hepatitis
- alcoholic hepatitis
- non-alcoholic steatohepatitis (NASH)
- primary sclerosisng cholangitis
- primary biliary cirrhosis
- drugs & toxins
- amoxicillin clavulanate
- alkylated anabolic steroids
- chlorpromazine
- Jamaican bush tea
- arsenic
- sepsis & other states of hypoperfusion
- infiltrative diseases
- amyloidosis
- lymphoma
- sarcoidosis
- tuberculosis
- total parenteral nutrition
- post-operative
- post organ transplantation
- hepatic crisis in sickle cell disease
- pregnancy
- end-stage liver disease
- hepatocellular injury
- parasitic infection
- Clonorchis sinesis
- Fasciola hepatica
- Budd-Chiari syndrome
- familial intrahepatic cholestasis
- thyrotoxicosis
- Alagille syndrome
- Caroli's disease
- protoporphyria
- pregnancy
- disorders of carbohydrate, lipid or bile acid metabolism
3) pharmaceutical causes:
- amoxicillin clavulanate (most common cause)
- anabolic steroids, androgens
- chlorpropamide
- erythromycin estolate
- gold salts
- methimazole
- nitrofurantoin
- oral contraceptives
- phenothiazines
Pathology:
1) plasma elevation of unconjugated bilirubin due to:
a) overproduction of bilirubin
b) impaired bilirubin uptake by the liver
c) defect in bilitubin conjugation
2) plasma elevation of both conjugated bilirubin & unconjugated bilirubin due to:
a) heptocellular disease
b) impaired canalicular excretion
c) biliary obstruction
Clinical manifestations:
- yellowish staining of the skin, sclerae, & other tissues with bile pigment (bilirubin)
Laboratory:
- serum bilirubin:
a) normal < 1 mg dL
b) in the adult, jaundice may become apparent when serum bilirubin > 2.5-3.5 mg/dL
c) in infants, serum bilirubin > 5-6 mg/dL for visible jaundice
- serum unconjugated bilirubin
- serum conjugated bilirubin (normal < 5% of total)
- serum delta bilirubin
- urine bilirubin
Special laboratory:
- abdominal ultrasound
- ERCP if biliary obstruction
- endoscopic ultrasound if biliary obstruction due to pancreatic mass suspected
Radiology:
- abdominal CT
- magnetic resonance cholangiopancreatograpy if pancreas appears normal on abdominal CT & biliary obstruction due to pancreatic mass suspected [4]
Management:
- see specific etiology
Related
hyperbilirubinemia
Specific
cholestatic jaundice
neonatal jaundice
General
hemolysis
References
- Harrison's Principles of Internal Medicine, 13th ed.
Companion Handbook, Isselbacher et al (eds), McGraw-Hill
Inc. NY, 1995, pg 829-39
- Saunders Manual of Medical Practice, Rakel (ed),
WB Saunders, Philadelphia, 1996, pg 361-62, 371-73
- Medical Knowledge Self Assessment Program (MKSAP) 16
American College of Physicians, Philadelphia 2012
- NEJM Knowledge+ Gastroenterology