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46 Cards in this Set

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describe the relative solubility and toxicity of unconjugated bilirubin and conjugated bilirubin
unconjugated- relatively insoluble in the blood, but is too large to get filtered at the glomerulus. solubility increased by binding to albumin, but unbound acts like a lipid and can cross BBB.
Conjugated- totally harmless event neonates. water soluble, and never albumin bound. small enough to be filtered at the glomeruli of the nephrons and is eliminated in the urine
kernicterus
Unbound unconjugated bilirubin can cross the BBB and is absorbed into the CNS neuron cell membranes forming a pathological inclusion that interferes with myelination
Which types if bilirubin cause jaundice
Unconjugated and conjugated!
Normal ranges for bilirubin in adults and neonates
Adult: total- 0.2-1.0 mg/dL
Direct- 0.0-0.4
Neonate- cord blood- less than 4.5
3-day less than 7.0
5- day less than 12.0
7-day less than 7.0 (all indirect)
Critical total bilirubin neonate-6months above 20mg/dl
Explain the breakdown of hemoglobin to conjugated bilirubin and urobilinogen
Hgb is broken down into bilirubin, iron, and blogin.
-bilirubin binds with albumin in the blood and then is acted on by blucuronyl transfer ease to make bilirubin diglucuronide(conjugated,direct)
-conjugated bill is excreted into the intestinesand bacterial enzymes convert urobilinogen into urobilins
- urobilinogens and urobilins are excreted in the feces at about 50-250 mg/day
How do we get indirect bilirubin form a bili assay
Total-direct=indirect
Or
Total-conjugated=unconjugated
Normal findings for urobilinogen and bilirubin in the urine
Both should be negative
Findings in pre-hepatic jaundice
Total bilirubin- 3.6mg/dl
Direct bilirubin- 0.3
Elevation is due to uncojugated
Urine urobilinogen- positive
Urine bilirubinn- negative
What is pre-hepatic jaundice seen in?
-normal neonatal physiological jaundice, gilberts, criggler-najjar
- hemolytic disease of the newborn
- acanthocytosis
- sickle cell or hemoglobinopathies
- transfusion reactions
What is hepatocellular jaundice seen in
Seen in any type of acute hepatitis, like hep A, B, C or chemical hepatitis
Values seen in hepatocellular jaundice
Total bilirubin- 4.2mg/dl
Direct bilirubin- 2.8
Elevation due to both conjugated and unconjugated
Urine urobilinogen is positive
Urine bilirubin is positive
What is hepatobiliary jaundice seen in? (post hepatic)
Primary biliary atresia- rare pediatric disease
Gallbladder diaease- choleostasis- extra-hepatic bile stone in gallbladder or intra-hepatic bile stone within liver
Values seen in post hepatic jaundice
Total bilirubin- 4.6mg/dl
Direct bilirubin- 4.2
Elevation due to conjugated bilirubin
Urine urobilinogen is negative
Urine bilirubin is positive
Explain gilberts syndrome and values
- a physiological jaundice
- total bilirubin 2.6
Direct bilirubin- 0.3
Elevation due to indirect
Urine urobilinogen is positive
Urine bilirubin is negative
Explain criggler-najjar
- usually a physiological jaundice
- total bill 2.6
- direct bill 4.2
Elevation due to indirect
Urine urobilinogen positive
Urine bili is negative
Explain dubin-Johnson syndrome and values
An obstructive physiological jaundice
-total bili-4.6
Direct bili- 4.2
Elevation is cue to conjugated bili
Urine urobilinogen is negative
Urine bili is positive
Specimen of choice for bili assays
Fresh unhemolyzed serum
-fresh unhemjolyzed heparinized plasma is an acceptable alternative
Specimen handling for bili assays
Protect from light- light labile
Keep cool- heat labile
Assay asap- degrades with time
Hemolysis will cause increased values if read at a wavelength below 600nm
Methods for bili assays
Nearly all analyzers use methods that are modifications of
Jendrassic Grof method
Evelyn Malloy Method
Both of these use a diazo reaction
Explain Evelyn-Malloy method
- uses a diazo reagent
- fractionation by solubility in polar vs. Non polar solvent.
- direct soluble in water
- total measured in ethanol
Rxn ended with red Azobilirubin and read below 600
Explain Jendrassic-Groff method
Uses a diazo reagent
- fractionation by solubility in pH
- direct soluble in HCL pH 1.3
- total measured in Acetate-Caffiene reagent (pH 8.0, caffiene is also a catalyst
- after Red Azobilirubin is formed fehling II reagent is added to shift the product to Blue Azobilirubin and read at 600nm
- hemoglobin interference is minimized
Precaution on pediatric bili levels
Dilute pediatric samples prior to analysis's appropriate to avoid redraws for more specimen.
- most analyzers have a linear range that is meant for adult values. Newborns can be 12-30 mg
Explain direct-reading bilirubinometers
Bili is a yellow chromophore so the sum level in a newborn may be directly measured in a bilirubinometer.
The specimen is a diluted sum or plasma
- a biggie for PCMC type hospitals
- vitros are replacing the need for bilirubinometers
Explain vitreous bilirubin slides
-uses two slides TBIL and BU/BC
- TBIL is a diazo rxn reading color using one wavelength
- BU/BC is a diazo rxn but the color is read at two wavelengths since bu and bc have slightly different absorbing spectra
Explain vitros neonatal bilirubin assay
TBIL slide is not FDA cleared for neonates under 3 weeks old and should not be used
- NBILI = total of BU and BC
- DBILI = BC portion of slide usually is very small
- during the first few days of life the neonate does not have any conjugated bili
Delta bilirubin
It was noticed that the TBILI was greater than the total of BU+BC in neonates and than was noticed among adults
- this occurred in patients with hepatitis and choleostasis.
- the difference between the TBILI and the BU/BC was called the difference or Delta bilirubin
- delta bili represents unconjugated bili that has been covalently bound to Albumin
Ammonia
-end product of protein and a amino acid catalbolism
- strongest naturally occurring base
- if ammonia builds up in the system it causes metabolic alkalosis
- very toxic to nereves causing shaking and spasms
- liver is the only organ able to detoxify ammonia by converting it to urea which is completely harmless
Reference range for ammonia
7-27 mol/L
- usually reported as mol/L Nitrogen
- low levels are fine, but high will cause alkalosos
Ammonia specimen handling
Specimen of choice is Heparinized plasma (green cap)
- keep in ice to slow enzymatic rxn and assay immediately
- keep specimen tightly capped until you actually perform the assay. Ammonia is volatile and will evaporate
Ammonia and urea levels and disease correlation
Elevated ammonia- hepatic disease
Low normal to decreased urea- hepatic disease
Normal values for plasma ammoia nitrogen
7-27 umol/L
Normal values for BUN and Urea
BUN- 7-18 mg/dL
Urea- 15-38 mg/dL
Normal values for creatinine
Serum/plasma
Males- 0.6-1.2 mg/dL
Females- 0.5-1.1
24 hr creatinine
Male- 800-1800 mg/day
Female- 600-1600
Normal values for creatinine clearance (GFR)
Males- 97-137 mL/min/1.73m
Females- 88-128
Normal values for uric acid
Males 3.5-7.2 mg/dL
Females 2.6-6.0
What is the conversion from bun to urea?
BUN x 2.14= urea
Azotemia
Elevated blod levels of non protein waste products, like BUN creatitnine uric acid
Uremia
End stage renal failure,
Azotemia plus other signs and symptoms of renal failure
Pre renal azotemia
Caused by Not perfusing the. Kidneys with blood, diet, and heavy metal poisoning
Renal azotemia
Caused by intrinsic damage to nephrons
- acute glomerulonephritis
- interstitial nephritis
- acute peel nephritis
- acute tubular necrosis
Hallmarks of acute glomerulonephritis
Prorenturia with tons of rbc and rbc casts
Hallmarks of pyelonephritis
WBC's, WBC casts, bacteria, and epithelial cells
Post renal azotemia
Caused by urethral obstruction, and kidney stones
Correlation between intra renal disease and creatinine levels
Each 0.1 mg/dl increase in serum creatinine corresponds to a 5-7% function loss
Pre renal azotemia BUN/creatinine ratios
>24
caused by shock, not perfusing the kidneys with blood
Intra renal azotemia BUN/creatinine ratios
<15
caused by damaged nepnrons