Clin Lab - Pediatrics Flashcards
What is an alkali denaturation test (Apt test) used for?
Differentiates maternal from newborn blood in blood fetal vomit/stool/aspiration
Does fetal Hgb denature in alkaline solutions?
NO
Does adult Hgb denature in alkaline solutions?
YES
Describe the make-up of adult hemoglobin (Hb A).
2 alpha & 2 beta chains
Describe the make-up of fetal hemoglobin (Hb A).
2 alpha & 2 gamma chains
Describe the alkali denaturation test (Apt test) process.
- Sample is mixed w/ 1% NaOH & color assessed
alkali denaturation test (Apt test) (+) test for adult hgb color
- yellow-brown color
- think tea/coca cola
alkali denaturation test (Apt test) (+) test for fetal hgb color
color–>pink
NOTE on newborn screening test
All states require a set of screening tests to look for congenital d/o
Major types of congenital newborn screenings?
- Congenital heart dz
- Hearing test
- Genetic d/o
What are the types genetic disorders screened in newborns?
- Errors of metabolism
- Hormone disorders
- Hemoglobinopathies
- Immune deficiencies
- other
Describe congenital heart dz screening.
Screens for critical congenital heart issues that cause hypoxemia & likely will need correction emergently or w/n 1st year of life
Examples of congenital heart dz?
- Tetralogy of Fallot
- Transposition of the great arteries
- Correction of the aorta
- Tricuspid or pulm atresia
When will hypoxemia likely become apparent?
O2 sats < 80%
What does the typical testing algorithm for congenital heart dz start with?
Test O2 sat using right hand & either foot
Why test the right hand & either foot?
Looking a perfusion (if coarctation we’re looking on above and below)
What is the timing go the newborn screenings?
- Initial screen >/= 24hrs after birth
- repeat screen at 1hr & 2hrs
Why is the initial new born screening measured >/= 24hrs after birth?
Babies can have normal transient hypoxemia
Positive screening test if any of the following are met:
- O2 < 90% in either extremity at any reading
- O2 90-94% in BOTH extremities on all 3 measurements
- O2 difference > 3% b/t extremities on all 3 measurements
If a newborn meets 1 of the criteria for a (+) screening for coarctation, does this mean they have it?
NO
If a (+) screening test for congenital heart dz, what happens next?
pediatric cardiology evaluation
- Need to also rule out causes of hypoxemia
What labs are done to rule out causes of hypoxemia?
- CXR
- CBC
- CMP
What imaging would look at the heart for a coarctation?
Echo
When should newborn tearing screening test be performed?
around 24hrs
What are the 2 types of hearing test for a newborn screening?
- Otoacoustic emissions (OAE)
- Automated auditory brainstem response (AABR)
Describe Otoacoustic emissions (OAE).
microphone placed in the ear canal detects sound waves generated in cochlea
Describe an automated auditory brainstem response (AABR)
sensors placed on head and neck detect action potentials in auditory nerve
Which type of hearing test is used in high risk newborns?
Automated auditory brainstem response (AABR)
Describe the 2 step screening for hearing issues.
Initial screen
- If (-), no further eval; monitor periodically at well child checkups
- If (+), repeat screening test in a few hrs
–> If (-) on 2nd screen, assume (-) but monitor closely
–> If (+) on 2nd screen, refer to audiologist
What are inborn disorders looking for on newborn screening?
abnormal level(s) of metabolites/ hormones/immune markers
How is the sample for testing obtained for inborn d/o?
blood from heel stick applied to test papers & sent to state labs.
When is the sample obtained for inborn d/o? Why?
close to discharge to allow max accumulation of markers
If the inborn d/o test is (+), what’s next?
will need further testing
List types of inborn d/o.
- Errors of metabolism
- Congenital hormonal disorders
- Hemoglobinopathies
- Immunodeficiencies
- Other genetic disorders
What are the results of an error of metabolism?
- accumulation of intermediate substance
- product def or
- toxic metabolite
What is an example of a dz cause by an error of metabolism?
Maple syrup urine dz
Pathophys of maple syrup urine dz.
- enzyme def in pathway that breaks down BCAA (leucine, isoleucine, valine).
- toxic metabolites cause distinctive smell of maple syrup in cerumen, urine, sweat
Errors of metabolism NOTE
Rare but serious genetic disorders
List the 4 categories of errors of metabolism.
- AA d/o
- CHO d/o
- Organic acid d/o
- FA d/o
Examples of amino acid d/o
- Phenylketonuria (PKU)
- Maple syrup urine disease
- Homocystinuria
Testing for amino acid d/o
serum AA levels
Examples of CHO d/o
- Galactosemia
- Glycogen storage dz
Testing for CHO d/o
serum CHO levels
Examples of organic acid d/o
- Propionic acidemia
- Methylmalonic acidemia
Testing for organic acid d/o
serum levels
What tends to occur w/ organic acid d/o?
metabolic acidosis w/ presenting sign of tachypnea
Examples of FA d/o
acyl-CoA dehydrogenase deficiencies
Testing for FA d/o
serum levels
Describe genetic penetrance
It is the severity of the condition
- lower penetrance = takes longer for substance to accumulate
- higher penetrance = take less for substance to accumulate
Possible lab findings of acute decompensation w/ errors of metabolism
- metabolic acidosis
- Hyperammonemia
- abnl LFTs
- -cytopenias from bone marrow suppression
- hypoglycemia
- elevated LDH
- elevated CPK
Describe labs findings for metabolic acidosis when acute decomposition in errors of metabolism.
- organic acid d/o
- low CO2 & HAGMA (adding an acid) on BMP
- Order ABG to prove
Describe Hyperammonemia & S/Sx.
Result of ammonia (think encephalopathy)
- lethargy poor feeding
- irritable
- restless
Describe labs findings for abl LFTS when acute decomposition in errors of metabolism.
AST/ALT elevation due to irritation of liver
Describe labs findings for acute decomposition in errors of metabolism.
WBC platelet are falling & anemia
Why would CPK be elevated?
muscle breakdown problem
Are all inborn errors are currently tested?
NO
Examples of congenital hormonal d/o?
- congenital hypothyroidism
- congenital adrenal hyperplasia
Describe Congenital hypothyroidism
Low levels of thyroid hormones lead to impaired cognitive and physical development
Pathophys: Congenital hypothyroidism
- thyroid dysgenesis (thyroid never formed)
- disruption of TH synthesis
- disruption of TSH receptor
- pituitary/hypothalamic d/o
Labs: Congenital hypothyroidism
- screening: dependent on state
–> Initial T4 test or initial TSH test or TSH/T4 combo test
–> All have false (-) & false (+) issues
Describe Congenital Adrenal Hyperplasia
Impaired production of adrenal cortex hormones leads to adrenal insufficiency
What is the most common reason for congenital adrenal hyperplasia?
21-hydroxylase enzyme
What is the result of the accumulation of 17-hydroxyprogesterone?
adrenal glands often become enlarged (hyperplasia)
Labs: Congenital adrenal hyperplasia
- Newborn screening: high 17-hydroxyprogesterone
- (+) lab findings: hypoNa+, hyperK+ (think Addison’s)
- (+) testing: adrenal US–>
Shows hyperplasia
Example of a hemoglobinopathies?
Sickle cell disease/trait
What is screened in sickle cell dz/trait?
- homozygous sickle cell dz (HbSS)
- sickle cell trait
- sickle cell/beta-thalassemia
- sickle cell/HbC
Is the initial screening test for sickle cell dz/trait confirmatory?
No, will need confirmatory test
Describe the SickleDex test.
Having 1 gene for sickling & will cause precipitation in medium
–> If cloudy–> sickle cell gene
–> If clear–> no sickle cell gene
–> Confirmatory Dx: electrophoresis
How many types of genetic immunodeficiencies are there?
Over 300
What do Congenital immunodeficiencies lead to?
early/severe/recurrent infx w/ high morbidity/mortality
What is the only congenital immunodeficiencies screened?
Severe Combined Immunodeficiency (SCID)
Severe Combined Immunodeficiency (SCID) causes…
Severe disruption of T cell development +/- B cell disruption
- Takes out the entire immune cell from working. Will still have some innate immunity
Severe Combined Immunodeficiency (SCID): Newborn screening test for?
TREC level – T cell receptor excision circles
What are TRECs?
small, circular pieces of DNA excised during development of T cells
Describe results of TREC levels.
TRECs will be low in newborns w/ SCID
–> means low immune function
Describe prehepatic neonatal jaundice
- Cause: Hemolytic anemia
- Liver is good, just overworked
- Clear biliary tree
- AST/ALT/Alk Phos normal
- High LDH & low haptoglobin
- High unconjugated (indirect)
- S/Sx: looks yellow, if affecting the brain–> lethargic)
- Tx: Phototherapy
Worried >24hrs–>damage to brain
Describe hepatic neonatal jaundice
- Cause: viral hepatitis, drug induced, autoimmune
- Liver is the problem
- High AST/ALT
- High unconjugated (indirect)
Describe post-hepatic neonatal jaundice
- Cause: biliary tree atresia, sphincter of Oddi narrowed
- High unconjugated (indirect)
Neonatal jaundice Diagnostic workup?
Obtain total & direct bilirubin measurements
If direct bilirubin >15% of total, this means…
conjugated hyperbilirubinemia
What are the causes of conjugated hyperbilirubinemia?
Causes:
- biliary atresia (Post heptatic), - hepatitis (hepatic)
- inborn error of metabolism (hepatic)
If direct bilirubin < 15% of total, this means…
unconjugated hyperbilirubinemia
Causes of unconjugated hyperbilirubinemia
- hemolysis (hemoglobinopathies - inherited membrane defect (hereditary spherocytosis or oval spherocytosis)
- bacterial sepsis
- autoimmune
- hemolytic dz of the newborn
What is further testing for direct bilirubin <15% of total? (unconjugated hyperbilirubinemia)
Direct antigen test (Coombs test)
Describe results of Direct antigen test (Coombs test) unconjugated hyperbilirubinemia.
DAT (+) = immune-mediated hemolysis
DAT (-)–> multiple other causes
- need to check Hct, retic count (2%), peripheral blood smear
–> Elevated Hct = polycythemia vera
–> Normal blood smear = blood loss, sepsis, drug rxn
–> Incr retic w/ abnl smear = hemoglobinopathy, membrane defect
Describe Corrected Retic Count Formula
(Hct/45 x retic count) x 100
Describe retic count values
- <2% bone marrow production problem
- > 2% destruction of RBCs
Neonatal sepsis: Early onset happens when?
birth to 5 days
What causes early onset neonatal sepsis?
- Group B Strep
- E coli
- Listeria
Workup for early onset neonatal sepsis?
- CBC w/ diff
- CMP
- Blood cultures
- CRP
- LP/CSF analysis (rule out meningitis)
- Other tests – UA, CXR, abd xray
Neonatal sepsis: late onset happens when?
6 days to 1 month
What causes late onset neonatal sepsis?
bacteremia or focal infection
- Same bacteria, + Klebsiella, S. aureus, Neisseria
Workup for late onset neonatal sepsis?
Same as early onset, but need to look for focal infx (CXR, UA, blood cultures, etc)
Which values are the same in Peds & Adults?
- Na/Cl
- BUN
- Ca
- Mg
Which peds lab values decrease over time?
- LFTs
- K+
- Phosphorus
Which peds lab values increase over time?
- Albumin (normal is 4)
- Hgb
- Cr
- Glucose
Which peds lab levels change in proportions?
WBCs
- initially lymphocytes predominant up to ~age 5, then neutrophils predominant
How do Intellectual & physical development typically occur…
in sequential patterns
For preterm infants, adjust for gestational age up to___ when assessing development.
2 years old
Developmental milestones are subdivided into…
- gross motor
- fine motor
- language
- social milestones
List screening tests for developmental milestones
- Denver Developmental II
- Parents Evaluation of Developmental Status (PEDS)
- Ages & Stages Questionnaire (ASQ)
What is evaluated at each visit & compared to standardized growth charts
height & weight
Failure to thrive parameters
Persistent weight < 3% or fall from prior level; flattened or decr growth curve
Causes of Failure to thrive
- Anemia
- bone marrow problem
- kidney/liver
- UTI
- nephrotic syndrome
Evaluation: Failure to thrive
- CBC
- CMP
- UA
- bone films
- As appropriate – TSH, IGF-1, IgA [autoimmune (celiac dz)], ESR/CRP
Obesity parameters
Weight is >95 percentile for age/height
What tests are considered childhood screening tests?
- Hgb
- Lead
- TB
- Dyslipidemia
Evaluation for Obesity
- fasting glucose (type II DM), CMP (liver/kidney/electrolytes), lipid panel.
- As appropriate – TSH (hypo), IGF-1 (GH), cortisol (Cushing synd)
When to screen Hgb?
1 yo
What hgb value needs further eval?
<11
Causes of low Hgb in peds
- not getting iron (hemoglobinopathy)
- vegan/vegetarian diet
When should evaluate for lead?
6, 9, 12, 18, 24 months & yearly thereafter
How is lead measured?
blood
What is measured next if lead levels are elevated?
measure zinc protoporphyrin (ZPP)
If ZPP is elevated, what does this mean? & Tx
lead exposure is chronic–>consider chelation therapy
What ages do you eval risk of latent TB?
1, 6, 12, 24 months & yearly thereafter
What is next if patient is deemed at risk?
PPD test or CXR
When should you not do a PPD test in child?
if vax or allergy
When to eval for CVD risk factors?
yearly
What are CVD RFs?
-smoke exposure
- HTN
- FHx
- CA
- DM
- systemic inflammatory dz
If patient has no RFs, what is next?
check lipid panel once at ages 9-11yo & 17-19yo
before & after puberty
If patient has 1 or more RFs, what is next?
check lipid panel at the time
What is evidence (signs) of abuse?
- bruising
- fractures
- burns
- any unexplained visceral or intracranial injury
If there is evidence/suspicion of abuse, what test are next?
- retinal eval
- skeletal survey
What is a retinal eval looking for in regards to child abuse?
retinal hemorrhaging
Describe a skeletal survey.
- done on kids w/ limited communication
- 21 separate x-rays
–> Old fractures or damage
Abuse signs: Abdo bruising/ tenderness is suggestive to what type of injury? How do you eval it?
- visceral injury
- CT abdo/pelvis
Abuse signs: Neuro deficit is suggestive to what type of injury? How do you eval it?
- Brain/cord injury
- MRI
Poss. not abuse: Bruising w/ petechia is suggestive to what? How do you eval it?
- bleeding disorder
- PT/INR & PTT, CBC (platelets)
Poss. not abuse: Multiple fx, low suspicion of abuse is suggestive to what? How do you eval it?
- bone d/o
- Vit D (low), CMP, EXA, Ca+ (low), Alk Phos, PTH, Mg (low)
