Ped Path Flashcards
Disruption
Extrinsic, mechanical force altering the development
Deformation
Extrinsic, biomechanical force altering development
Malformation
Intrinsic/genetic force altering development
Malformation: epidemiology
Idiopathic: 60% Multifactorial: 25% Chromosomal abnormalities: 10-15% Maternal disease states: 6-8% TORCHES: 2-3%
Viral susceptibility: time frame
From just before conception - 16 weeks
Alcohol as a teratogen
Disrupts signaling of retinoic acid and sonic hedgehog
Thalidomide teratogenicity
Upregulates WNT suppressors
-
Nicotine effect on fetus
SGE, prone to SIDS
Maternal diabetes effects
Hyperglycemia -> fetal hyperinsulinemia -> acts as GF increasing both size and rates of organ abnormalities
Sensitive period
3-8 weeks
- neurulation occurs earliest and has greatest susceptibility
Cyclopamine
Screws with sonic hedghog, can result in sever NTDs
Valproic acid as a teratogen
Causes mutations in the HOX genes
Vitamin A (retinol)
It’s essential for organogenesis, but too much can result in retinoic acid embryopathy. May be associated with messed up TGF-B
Gestation time: risk factors for early parturition
Prematurity is the second leading cause of infant mortality.
- premature rupture of membranes and intramniotic infection are common causes
- structural abnormalities
- multiple gestations
Risk factors for newborns
Weight trumps appropriateness for age
Fetal growth restrictions; fetal and maternal factors
- maternal factors: hypertension, preeclampsia, hypercoagulable states
- fetal (represented by symmetric abnomalities) and placental (represented by asymmetric abnormalities) factors also play a role.
Risks for preterm infants (5); 2 organ systems, 2 systemic risks
Hyaline membrane disease Necrotizing enterocolitis Sepsis Intervenous hemorrhage Long term complications
Neonatal RDS: etiology, risk factors (3)
Etiology: underdeveloped lung tissue -> little/no surfactant ->contributing to hyaline membrane disease
- male, c-section, maternal diabetes risk factors
Surfactant A/B vs. C/D
A/B - immune function: innate defense
C/D - reduction in surface tension
- surfactant controlled by SFTPB/SFTPC
Chemical mediators if surfactant
TGF-B and corticosteroids stimulate it
Insulin inhibits it
Bronchopulmonary dysplasia
Rare in infants over 1200 g
- high lvls of O2 contribute to development
- inflammatory cytokines increase
- if they survive past 4 days recovery can be expected at ~ 31 weeks.
Transcervical vs. transpalacental infections
Transcervical: mostly bacteria (some viruses like HSVII). In fetus infections is typically respiratory (inhaled amniotic fluid) and sepsis
- transplacental: most parasites, TORCHES viruses, listeria, treponema pallium
TORCH effects
Fever, encephalitis, hepatosplenomegaly, pneumonitis, myocarditis, hemolytic anemia, vesicular damage, and hemorrhagic skin lesions
Immune hydrops
- aka hemolytic disease of the new born. Can result in anemia, kernicterus, or hydrops from cardiac decompensation
- The D antigen is the major cause of Rh incompatibility
- occurs only after significant trans-placental bleeding
- administration of Anti Ab Ig happens at 28 weeks to prevent sensitization, and again within 72 hours of delivery.
PKU
- Most commonly it the Absence of phenylalanine hydroxylase-> accumulation of Phe
- it may also be reduced TH4 (phe doesn’t get oxidized to tyrosine) this form will not be treated by reducing phe intake.
- control of maternal PKU is ESSENTIAL during pregnancy. Elevated Phe lvls are devastating to baby.
Galactosemia
- primarily a deficiency of GALT
- leads to the G-1-P accumulates and is toxic. (Cataracts and DD are two giveaways)
- hepatomegaly happens early, FTT is also early
- may also have frequent E. coli septicemia
- trt by removing galactose from diet
Cystic fibrosis
- CFTR gene mutation -> bad chloride channels as well as ENaCs, and k channels
- channels are cAMP mediated
- the sweat gland ENaC channels aren’t CFTR controlled, resulting in high sodium AND high chloride sweat
- decreased luminal pH from lack of Bicarbonate transport contributes to obstructions
6 classes of CF
I. Defective protein synthesis
II. Abnormal protein folding: most common (delta F508)
III. Defective regulation
IV. Decreased conductance
V. Reduced abundance
VI. Altered regulation of separate ion channels
- types I,II and III are the most
Phenotypic differences among CF PTs.
TGF- B and MBL are both influenced by the CFTR gene and are involved in innate immunity.
Heterotropia
Heterotrophic tissue is normal tissue in a an abnormal place
- lipoma
- hamartoma
Anaplastic lymphoma kinase (ALK-1)
The major cause of neuroblastomas
Homer-wright pseudorossets
Small, scant cytoplasm containing cells compacted in a tumor represent a histologically classical neuroblastoma
Ganglioma
Similar to Neuroblastoma accept the ganglioma contains mature ganglion cells
Schwannian stroma
Represents a more favorable prognosis
Neuroblastoma prognosis
Age and stage are most important prognostic factors
- 18 mo is the turning point
Amplification of the N-MYC gene is the most important independent factor
N-MYC in neuroblastomas
Hemizigous deletion of distal short arm found in 25-35% of primary tumors
Partial gain of distal long arm is present in up to 50% of tumors
Wilms tumor
- renal tumor that typically occurs from Age 2-5 up to about age 9
- follows two hit hypothesis
- WAGR syndrome has higher risk of developing the Wilms tumor
Denys-drash syndrome
- male pseudohermaphroditism
- early onset neuropathy
- Germ line abnormalities in WT1 gene (biallelic activation)
WT-1
Gene associated with development of Wilms tumor
Beckwith-weiderman syndrome
- organomegaly
- microglossia
- hemihypertrophy
- gene abnormality near locus of WT-1: Associated with Wilms tumor
IGF-2
Paternally imprinted insulin like growth factor
- when its over expressed can lead to development of Wilms tumor
Nephrogenic rests
Putative precursor lesions to a Wilms tumor
- Associated with some unilateral Wilms tumors and almost all bilateral Wilms tumors
Oxygen toxicity
Contribute to Bronchopulmonary dysplasia
Frequent early E. coli septicemia
May indicate Galactosemia, Especially if accompanied by failure to thrive
Male, c-section, maternal diabetes
Risk factor for neonatal RDS
Symmetric vs. asymmetric fetal abnormalities
Symmetric: fetal factor
Asymmetric: placental factor
Maternal fetal growth restrictions
It’s all about blood flow: HTN, hypercoagulable states
