Jaundice Flashcards
Jaundice?
yellow/green appearance to the skin & eyes (Icterus) produced by increased serum bilirubin
- Usually given in a direct/total relationship
Normal bilirubin ranges?
- ranges 0.5 to 1.0 mg/dl.
- Levels >3.0 mg/dl to be clinically jaundiced
N.B. the Newborn period is the exception
Describe bilirubin metabolism?
- Red cells (Heme) break down forming biliverdin (bile pigment)
- This is unconjugated (indirect bilirubin). - It is transported by albumin & is not soluble - No Bilirubin in the urine
- The bile pigment is converted to conjugated (Direct bilirubin) by the Kupffer cells of the liver.
- In the liver, the bilirubin is conjugated
with UDPglucuronate, making it water-soluble Bilirubin diglucuronide
i.e. (“direct” conjugated bilirubin).
- This is soluble & only shows up in blood & urine with obstruction in the system
Describe Bilirubin conjugation?
- In the terminal ileum the bilirubin is converted to stercobilinogen & urobilinogen by natural bacteria
- Conjugated bilirubin is excreted into the bile and passed into the intestine where it is further metabolised
- urobilinogen ->urobilin-> stercobilin, which colors the feces brown
- Some is reabsorbed and returned to the liver - Some urobilinogen is found in the urine
- If excretion of conjugated bilirubin is hindered, it is excreted by the kidney
Causes of Pre-hepatic jaundice?
hemolytic disease
Causes of Post-hepatic jaundice?
- Hepatitis
- Drug induced hepatitis
- Cirrhosis
Causes of Obstructive jaundice?
- gallstones
- pancreatic cholangio carcinoma
- liver fluke - schistosomiasis
Consequences of obstructive jaundice?
- Obstruction of biliary system prevents production of urobiligen & stercobilinogen
- Stool is light and urine is dark showing bilirubin
Classification of hyperbilirubinemia?
- Increased bilirubin production
- Decreased bilirubin uptake by the liver
- Impaired conjugation in the liver
- unconjugated (indirect) = normal stool and urine color - Decreased excretion of bilirubin into the bile (cholestasis)
- conjugated bilirubin (direct) with dark urine and light stool color
Causes of unconjugated (indirect) hyperbilirubinemia?
- Due to overproduction
- decreased hepatic uptake
- decreased conjugation of bilirubin
Causes of over production of unconjugated bilirubin?
- secondary to hemolysis (autoimmune)
- ineffective erythropoiesis (megablastic anemia)
- increase RBC fragility/turnover (2,3 DPG deficiency)
Causes of impaired hepatic uptake of UB leading to hyperbilirubinemia?
- Gilbert’s syndrome
- certain drugs such as rifampin, anesthetics & radiographic dyes
Causes of impaired conjugation that lead to UB hyperbilirubunemia?
- Hepatocellular disease
- drug inhibition such as chloramphenicol, anabolic steroids
- genetic disorders such as Gilbert’s syndrome or Crigler- Najjar syndrome (decreased UDP-glucuronyl transferases).
What is the most common cause of jaundice?
neonatal jaundice
What makes newborns susceptible to having jaundice?
They do not have a significant quantity of glucouronyl transferase (the enzyme used for conjugation), due to enzyme immaturity, but kicks in within a few weeks
What is kernicterus?
- is a type of brain damage caused by build up in unconjugated bilirubin in the brain
- that causes athetoid cerebral palsy and hearing loss
- It also causes problems with vision and teeth and sometimes can cause mental retardation
How to treat neonatal jaundice?
UV light is used to isomerize the bilirubin, which prevents it from crossing the blood-brain barrier.
What causes neonatal jaundice?
- Rh disease/ABO incompatibility is hemolytic
- impaired hepatic intake
Causes of conjugated (direct) hyperbilirubinemia?
- Altered biliary drainage
- impaired hepatic excretion of bile
- extra hepatic obstructions
- cholestatic jaundice
Causes of altered biliary drainage of bile leading to CB hyperbilirubinemia?
- TPN, cholestasis, drugs
- hepatocellular disease
- cirrhosis
Note:
- May occur in setting of cholestasis with impaired formation or excretion of all components of bile or hepatocellular injury independent of cholestasis.
- May indirectly cause increase in unconjugated also if severe enough
Causes of impaired hepatic excretion that leads to CB hyperbilirubenemia?
- intrahepatic cholestasis
- Dubin-Johnson syndrome & all disorders in the transport of conjugated bile from the hepatocytes to intrahepatic bile ducts.
- Drug-induced cholestasis
- phenothiazines, OCP’s & methyltestosterone
Extra hepatic causes of CB hyperbilirubinemia?
- Gallstones
- pancreatic/biliary obstructive tumors and strictures
- biliary atresia
Characteristic features of conjugated hyperbilirubinemia?
Dark brown or green urine implies conjugated hyperbilirubinemia
What is cholestatic jaundice?
Increased alk phos to 3-4 times normal.
Features of cholestatic jaundice?
- Hypercholesterolemia
- pruritus
- malabsorption of fat & fat-soluble vitamins
- Minimal or marked evidence of liver cell damage.
How do you diagnose conugated hyperbilirubinemia?
through history
1. pale stools & pruritus–> cholestasis.
2. nausea–> gallstones = biliary obstruction.
3. Inquire about drugs & alcohol use, risks for viral hepatitis & pre-existing liver disease.
Laboratory Diagnosis of conjugated hyperbilirubinemia?
- biliary obstruction: <5-10 fold increase in transaminases & >2-3x normal alk phos.
- Hepatocellular disease: >10-15 fold increase in transaminases & < 2-3x normal alk phos.
Disorders of the biliary system?
- sepsis
- post-op jaundice
- hepatocellular disease - hepatitis, cirrhosis
- extrahepatic biliary obstruction
Diagnosing sepsis?
- mainly gram-negative organisms.
- Mildly elevated serum alk phos
Diagnosing post-op jaundice?
- happens 1-10 days post-op
- 15% incidence following heart/ 1% elective abdominal surgery
- Increased alk phos & minimally elevated levels of transaminases
- Secondary to anesthesia side effects
Diagnosing hepatocellular disease?
elevated transaminases, prolonged PT, hypoalbuminemia & clinical features of hepatic dysfunction.
Diagnosing extrahepatic biliary obstruction?
- obstruction of extra hepatic bile ducts–gallstones, neoplasias, bile duct strictures, chronic pancreatitis.
- Clay-colored stools.
Name Special diagnostic procedures in cholestatic jaundice?
- Extra hepatic obstruction
- CT or U/S to determine stone or bile duct dilation. - Bile duct dilation
- endoscopic retrograde cholangiography (ERCP) for management & treatment. - Liver biopsy
- for determining cause of intrahepatic cholestasis
