Lecture Week 3 Flashcards
What can jaundice be caused by
what are pathological cases of jaundice
Un conjugated and conjugated bile
when in unconjugated bili increased
physiological jaundice of newborn
HDN
Breast milk hyperbilirubinemia – Something in breast milk which prevents baby’s liver from processing unconjugated bilirubin
-Gilbert syndrome (pathological)
-Crigler-Najjar syndrome (pathological)
Conjugated in increased in :
Idiopathic neonatal hepatitis – Inflammation of liver
-Biliary atresia – Blockage/ absence in bile duct
Dubin-Johnson syndrome
What is the enzyme that catalyzes the conjugation of bilirubin?
UDP glucoral transferase - last to develop in the fetus
Physiological Jaundice - Causes 3
1) decreased conjugation
when you have all 3 you have increased amount of unconjugated bilirubin which is carried by albumin, This cant be excreted easily by babies . Premies are most at risk
increase in unconjugated bilirubin within first few days after birth while conjugated bilirubin levels are normal can be caused by:
enzyme deficiency
-lack of UDP-glucuronyl transferase in first few days-enzyme is one of the last liver functions to be activated in prenatal life
-breast milk pregnanediol (female hormone involved in metabolism of progesterone)
inhibits bilirubin conjugation
Physiological Jaundice - Causes
2)) increased bilirubin load
-babies are born with high levels of RBC so when body starts removing old RBC after birth the increased RBC destruction can increase bilirubin load
-baby RBC have a lifespan of 90 days
Physiological Jaundice - Ranges
unconjugated bilirubin
unconjugated bilirubin
-peak 3-5 days after birth and stay high for 2-4 weeks
-normal is 85umol/l
-as the babys liver enzyme liver system develops the levels decrease
-anything about 170 umol/l is pathological in that it can produce disease process and if the baby has low albumin - bilirubin neurotoxicity
Physiological Jaundice - Causes
increased absorption of bilirubin in intestine
beta-glucuronidase in meconium
-enzyme in gut deconjugates bilirubin (Bc) (converts conjugated to unconjugated – this is absorbed into the blood and then liver)
-hydrolyzes Bc to Bu that is then passively reabsorbed (enterohepatic pathway)
Pathological Jaundice with increases in Unconjugated Bilirubin
Hemolytic Disease of Newborn (HDN)
after birth baby cord blood will be sent to transfusion for type and screen , DAT
-there is an Rh incompatibility between the antiD on Rh negative mom and Rh positive fetus
-Rh neg mom makes Anti-D that will attack Rh pos baby’s RBCs – causing increased RBC destruction
-baby becomes jaundiced in 24 hours
- Breast milk hyperbilirubinemia
-Breast milk may contain beta-glucuronidase which is the enzyme found in baby’s gut that can deconjugate bilirubin
Crigler-Najjar Syndrome
pathological jaundice
inherited autosomal recessive
-absence of UDP glucuronyl transferase (bili will not get conjugated)
-increase in unconjugated bilirubin
-most die of kernicterus (biliburin deposited in the brain) within 1st year of life
-early liver transplant is only effective therapy
Gilbert Syndrome
benign condition
inherited autosomal recessive
UDP enzyme activity is decreased so it’s less effective
only mild increases in unconjugated bilirubin
often misdiagnosed as chronic hepatitis
not as severe as Crigler- Najjar
Pathological Jaundice with increases in Conjugated Bilirubin
Dubin-Johnson Syndrome:
Liver is functioning properly, able to take in unconjugated bili and conjugate it. It cant remove the conjugated bili and excrete into bile
. Thus conjugated bilirubin will be leaked into the system
benign
inherited, autosomal recessive
elevated conjugated bilirubin & minor elevation of unconjugated bilirubin
Delta bilirubin – Conjugated + albumin in circulation
Measured in total bilirubin test results
Pathological Jaundice: with increases in Conjugated Bilirubin
Idiopathic neonatal hepatitis:
-unknown etiology
-characterized by cholestatic jaundice
appears within first 2 weeks of birth
treatment is supportive
-Affects transport of bilirubin
Pathological Jaundice: with increases in Conjugated Bilirubin
Biliary atresia (in utero):
-acquired or secondary disorders
virus, Down Syndrome, trisomy 17/18
-absence of extrahepatic or intrahepatic ducts (bile ducts may be present but are narrowed or openings missing/ gall bladder may be absent)
-drainage of bile can be surgically repaired for extra-hepatic
-liver transplant may be required
What is Kernicterus
-can be caused by Hyperbilirubinemia
-resulting from bilirubin neurotoxicity
-increase in free unconjugated bilirubin (not bound to albumin) cross blood-brain barrier
-bilirubin more lipid-soluble than water- soluble: deposits in nuclei of neurons
-brain tissue on autopsy is stained yellow
-Build up of unconjugated bilirubin in brain
-necrosis of the cells of the basal ganglia & hippocampus
-infants get seizures and if they dont pass they have severe brain damage, auditory issue
-had almost disappeared because mom are given Rh immune globin injections preventing them from making Anti-D that attacks baby’s RBCs . But because babies are getting discharged earlier right after birth they have to be readmitted for high bilirubin
Specimen Timing, Treatment Guidelines
bilirubin levels or transcutaneous (measured from skin) be done within first 24 h of birth, or before discharge
-we need to look bilirubin because it helps is see which newborn needs to be treated
pre-discharge total bilirubin level
gestational age
higher risk if pre-term (<37 weeks)
less albumin to bind bilirubin in plasma
birth weight < 2500 g
age in hours after birth
presence of any hemolysis due to maternal blood incompatibilities
overall health of the infant
The older the baby is, if their total bilirubin is still high, then they’re at high risk for hyperbilirubinemia
Hyperbilirubinemia: Treatment
phototherapy
remember inconjugated bili is not water soluble
photoisomerisation with blue light (450 nm) converts unconjugated bilirubin to nontoxic, water-soluble isomers that are excreted in urine
In severe cases:
exchange transfusion may be required for severe HDN (pathological jaundice)
Measuring Neonatal Bilirubin
POCT: Transcutaneous bilirubin
-reflects light from skin
-measurement without using a needle
-uses many wavelengths so there is not discrepancy if baby is melanated
Direct Spectrophotometric
-undiluted serum -NEOTATES ONLY because babies dont have carotene
-bilirubinator
-ABs at 454 nm and only measures UNconjugated bili
-subtraction of absorbance at 540 nm corrects for presence of oxyhemoglobin (hemolysis)
Diazo methods
-capillary blood by heel prick or venous
Unconjugated is a CALCULATED amount
Hyperbilirubinemia: additional lab testing
bil, Bu, Bc, we can test for:
Albumin: reflects Bu carrying capacity
Transfusion testing
ABO & Rh
antibody screen
direct antiglobulin test (DAT)
Hematology testing
CBC: Hb, Hct, Diff
When you test for bilirubin what do you look for
- testing for liver function , its ability to absorb , conjugate and excrete into the bile
-we need to know how much and what type
-increases can be caused by
increased production (hemolysis)
decreased uptake by the liver
decreased conjugation
decreased secretion from the liver
bile duct blockage discussed previously
inherited disorders (Gilbert syndrome, Crigler-Najjar, Dubin-Johnson)
What type of specimen is needed for bilirubin
-serum or plasma
-bilirubin is photo-sensitive (destroyed by light) can decrease 30-50x if not covered
-protect samples from sunlight or fluorescent light if not being analyzed immediately
-use dark-colored (tinted) containers or wrap in foil to protect from light exposure
What is the Jendrassik-Grof Method of measuring total bilirubin
AU480 machine - needs a sample blank to remove endogenous serum interference
Diazo reagent: Sulphanilic acid in Hydrochloric acid and Sodium nitrite
*Accelerator: Caffeine-benzoate Solubilizes the water in unconjugated bilirubin by dissociating it from albumin
-Tbil reacts with Daizo to produce Azobilirubin. Followed by the addition of Ascorbic acid which destroys the Diazo reagent not used . Tartrate is added to make the solution alkaline = blue color . pH is important because itll change it to the color we measure at
U480 measure azobilirubin at 570-660 nm.
-intensity of the blue colour is proportional to the concentration of the total bilirubin
In other pH, azobilirubin could be pink. It just depends on the instrument were using
