Heme degregdation Flashcards
1
Q
Jaundice
A
- clinical sign-yellowish discoloration of skin, mucous membranes, sclera and nail beds
- binding of bilirubin to connective tissue
- when bilirubin levels are greater than 2 mg/dL (hyperbilirubinemia)
- normal serum bilirubil are <1 and mostly unconjugated
2
Q
Formation of bililrubin
A
- occurs in macrophages (reticuloendothelial/mononuclear phagocyte system) mostly in spleen and liver
- heme oxygenase leads to biliverdin (green pigment)
- biliverdin reductase: forms bilirubin (yellow-orange color)
over all uses 2 NADPH and leavse you with Fe3+ and CO
3
Q
Heme Oxygenase
A
Heme + NAPDH + O2 ——>NADP+ + Fe3+ + CO + Biliverdin
4
Q
Biliverdin reductase
A
Biliverdin + NADPH ——> Bilirubin + NADP+
5
Q
Bilirubin transport
A
- unconjugated bilirubin is not water soluble and is transported bound to albumin
- unboud bilirubin can be excreted in urine
- bilirubin can be diplaced from albumin by drugs such as salicylates and sulfonamides and cause kernicterus in children
6
Q
Uptake of bilirubin into liver
A
- has specific transporter
- binds ligandin inside hepatocyte
7
Q
Conjugation of bilirubin
A
Microsomal UDP-glucuronyl trasferase
Bilirubin + 2 UDP=glucuronic Acid—->Bilirubin diglucuronide (conjugated bilirubin) + 2 UDP (enzyme really works 2x)
Defect in Gilbert Syndrome and Crigler-Najjar Syndrome (types I and II)
8
Q
Formation of urobilinogen
A
- conjugated bilirubin is actively transported against gradient into bile canaliculus by a specific ABC transporter
- decongugated by bacterial flora in large intestine converted to urobilinogen (colorless)
- some urobilinogen is reabsorbed into portal circulation (10%)–>eventually secreted into urine as yellow pigment urobilin
9
Q
Formation of stercobilin
A
-also done but intestinal flora, lost in feces, is a brown pigment, gives feces brown color
10
Q
Bilirubin tests
A
Van den Bergh reaction
- bilirubin reacts with diazo reagent (diazotized sulfanilic acid) to form a red colored complex
- conjugated bilirubin is water soluble and reacts rapidly–>direct bilirubin
- total bilirubin: do the reaction with methanol and both react
- Indirect (unconjugated)=total-direct
11
Q
Classifications of Jaundice
A
- Prehepatic/hemolytic: increased breakdown of RBCs
- hepatic: decreased conjugation and decreased excretion
- posthepatic/obstructive: decreased excretion of bilirubin via bile, stone
12
Q
Prehepatic/hemolytic Jaundice
A
- total serum bilirubin super up
- no serum conjugated bilirubin
- serum uncojugated bilirubin super up
- urine bilirubin absent
- urine urobilinogen up
- inceased hemolysis leads to increased formation of bilirubin
- increased unconjugatd bilirubing boud to albumin (contributes to most of the increased serum bilirubin)
- increased bilirubin conjugation in the linger–>more bilirubing into bile–>more urobilinogen in intestine–>increased urobilin in urine and stercobilin in feces
13
Q
Hepatic Jaundice
A
- Total serup bilirubin up up
- conjugated bilirubin up
- unconjugated bilirubin up
- urine bilirubin present (conjugated)
- urine urobilinogen no or down (or sometimes a little up)
- Also elevated ALT and AST
- caused by liver damage like viral hepatis or cirrhosis
- decreased uptake and conjugatation and secretion by liver
- increased conjugated bilirubin in circulation due to regurgitation–>lost in urine
- decreased excretion of conjugated bilirubin into bile and intestine–>less urobilinogen–>less urobilin and stercobilin
14
Q
Post Hepatic Jaundice
A
- Total bilirubin up up
- conjugate bilirubin up up
- serun unconjugated bilirubin normal
- urine bilirubin positive
- urinine urobilinogen down or absent
- Elevated ALP
- caused by obstruction of bile aparatus by gall stones or cancer
- conjugated bilirubin is regurgitated into blood
- no conjugated bilirubin makes it into the intestines
- pt looses weight b/c they don’t absorb fats
- urobilin absent in urine, clay colored feces (light b/c no stercobilin)
15
Q
Jaundice in newborn
A
- neonates have low activity of hepatic UDP-glucuronyl transferase (especially premies)
- increased destruction of RBCs overloads liver’s capacity to conjugate
- increased unconjugated bilirubin
- jaundice by 2nd or 3rd day usually clears up by 7th day (Use lights to break down bilirubin to more soluble forms that can be excreted in bile without conjugation)
- increased unconjugated bilirubin can cross blood-brain barrier to cause kernicterus–>lethargy, althered muscle tone, high pitched cry
- severe permanent neurologic symptoms (choreoathetosis, spasticity, muscular rigidity, ataxia, mental retardation)
- risk increased with hypoalbuminemia, low pH and certain drugs
