Robbins Chapter 10 Flashcards
4 common causes of death in infants < 1 yo (CPSM)
- congenital malformations
- prematurity
- SIDS
- maternal complications
4 common causes of death in 1-4 yos (ACAM)
- accidents
- congenital malformations
- assault
- malignant neoplasms
4 common causes of death in 5-9 yos (AMCA)
- accidents
- malignant neoplasms
- congenital malformations
- assault
4 common causes of death in 10-14 yos (AMSA)
- accidents
- malignant neoplasms
- suicide
- assault
Teratogens (Valproic Acid and All-Trans RA)
VA (antiepileptic)
- disrupts HOX proteins –> weird limb development
- mimicked by HOX gene defects
AT RA (accutane –> acne)
- excess = CNS, cardiac, palate deformities
- mimicked by TGF-beta
Moderate-Late, Very, and Extremely Preterm time frames
ML: 32-37 weeks
Very: 28-32 weeks
Extremely: < 28 weeks
4 major risks for Prematurity (PISM)
- Preterm Premature Rupture of Membranes
- infection of amniotic space
- Intrauterine Infection –> 25%
- Structural Abnormalities
- Multiple Gestation (twin pregnancy)
Fetal vs Placental vs Maternal FGR
F - congenital problems, TORCH infections
symmetric restrictions = organs affected equally
P - heavy placental blood burden (3rd trimester)
- fetus growth outpaces nutrient supply
- *asymmetric restrictions = brain spared**
M - MOST COMMON (dec. placental blood flow)
- preeclampsia, HTN, malnutrition, drugs, alcohol
What are the three biggest risk groups for Neonatal Respiratory Distress Syndrome? (MMC) What would the physical exam reveal about these patients?
males, maternal diabetes, C-section
- fine rales in lung fields, ground-glass densities on chest X-Ray
Neonatal Respiratory Distress Syndrome
- deficient in SP-B, SP-C, and surfactant lipids (check in the amniotic fluid) –> Type II Pneumocytes
- progressive atelectatic lungs and reduced membrane compliance = hyaline membrane formation
- hypoventilation = acidosis and pulmonary vasoconstriction
What two things increase surfactant synthesis and what two things decrease surfactant synthesis? What does prognosis of NRDS depend on? (2 things)
Increase: labor and cortisol (glucocorticoids)
Decrease: insulin (diabetic mother) and C-section
Prognosis depends on: maturity and birth weight
Retrolental Fibroplasia and Bronchopulmonary Dysplasia (Complications of Ventilator Oxygen)
RF: VEGF rebound after loss of high oxygen lvls from ventilator = retinal vessel proliferation
BD: dec. alveolar septation (large, simple alveoli), happens at the saccular stage
- inflammatory cytokines can cause
What 3 things are NRDS patients who recover at risk for?
Patent Ductus Arteriosus, Intraventricular Hemorrhage, Necrotizing Enterocolitis
Necrotizing Enterocolitis (NRDS risk)
enteral feeding where bacteria is introduced to infant
Platelet Activating Factor (PAF) –> enterocyte apoptosis = gut microbes cause inflammation
Pneumatosis Intestinalis
Presentation and Management of NEC
BLOODY STOOL, DISTENSION, SHOCK
terminal ileum, cecum, right colon = commonly
- resection of necrotic bowel (post strictures)
coagulative necrosis, ulceration, bacterial colonization, submucosal gas bubbles (pneumatosis intestinalis)
Transplacental vs Transcervical Perinatal Infections
TP: parasitic/viral (mostly) –> fetal bloodstream
TC: bacterial (mostly)
- breath amniotic fluid or passing through canal
Early Onset vs Late Onset Perinatal Sepsis
EO - 7 days of life
- from group B strep (pneumonia, sepsis, meningitis)
LO - 7 days to 3 months
- from listeria/candida (sepsis)
Immune Hydrops (Rh and ABO) and Protection
Rh –> mother (Rh-) makes IgG after first pregnancy that can attack future Rh+ babies
- D antigen (from father)
- use Rhesus (RhIg) –> rhogam (anti-D antigen)
ABO –>A/B fetus with O mother that have anti-A/B Abs that are IgG
- NO effective PROTECTION
When should Rhesus be administered to mothers that are Rh(-)?
at 28 weeks and 72 hours after delivery or abortion of first pregnancy
What 3 things can cause non-immune hydrops? (CCF)
- CV defects
- Chromosomal Abnormalities (Turner, 18, 21)
- cystic hygromas is Turner
- Fetal Anemia NOT of Rh/ABO cause
- alpha thalassemia and Parovirus B19
Classical Phenylketonuria cause and presentation (5 major things)
deficient phenylalanine hydroxylase (PAH) = hyperphenylalanemia (treated with diet restriction)
- mental retardation in 6 months, seizures, dec. pigment, eczema, and MUSTY/MOUSY ODOR
2% of cases due to cofactor BH4 that CANNOT be treated with diet
When should mothers with PKU restrict phenylalanine during pregnancy?
restrict diet prior to conception and throughout prenancy
- metabolites act as TERATOGENS = mental retardation, microcephaly, congenital heart disease
Galactosemia cause and presentation (4 major things)
deficient Galactose-1-phosphate uridyl transferase
- accumulation of Galactose-1-phosphate
- galactokinase deficiency (Rxn 1) = RARE
- cataracts (galactitol accumulation), edema in DENTATE and OLIVARY nuclei (mental retardation less severe than PKU), aminoaciduria, hepatomegaly
FAILURE TO THRIVE (remove milk in first 2 years)
Cystic Fibrosis cause and presentation (4 major things)
3 base deletion on Chromosome 7q31.2
- defect in protein folding in golgi/ER
- reoccurring lung infections, pancreatic insufficiency, and steatorrhea, MALE INFERTILITY
CFTR gene and ENaC (airway vs sweat duct)
Airway: inhibited by normal gene
- inc. uptake of Na across apical membrane in CF
- dryer mucus (hyperconcentrated)
Sweat Duct: ENaC activity DECREASES (opposite)
- reduced Na absorption from sweat
- SALTY Babies (diagnostic)
CFTR and Bicarbonate Transport (Pancreatic Insufficiency)
SLC26 coexpressed with CFTR
- responsible for bicarbonate ion transport
- problems = acidic secretions (normally alkaline) that cause mucin precipitation and duct plugging
What 3 modifiers of Neutrophil action inc. the severity of Pulmonary Disease in patients with Cystic Fibrosis? (MTI)
mannose-binding lectin 2 (MBL2), TGF-B1, interferon related developmental regulator 1 (IFRD1)
What are the 3 most common bacteria that infect the lung and what opportunistic bacteria is most common in CF patients?
top 3: S. aureus, H. influenza, P. aeruginosa
Most common in CF patient: B. cenocepacia
- cepacia syndrome, longer hospital stays, inc. death
What are two common GI features of CF and what nasal abnormality can indicate testing a child for CF?
GI: meconium ileus and intussusception in RLQ
- telescoping of colon
Sinonasal polyps occur in 10-25% of patients but are good indicators that a child should be tested for CF
What ages are associated with:
- Neonatal period
- Infancy
- Toddler/preschool
- School Age
- first 4 weeks of life
- up to age 1
- age 1-4
- age 5-14
When does SIDS usually occur? What is its most common finding?
mostly occurs between 2nd and 4th month of life
- leading cause of death between 1 month and 1 year
commonly seen with: multiple petechiae on thymus, visceral/parietal pleura, and epicardium
How is SIDS associated with Arousal and Cardiorespiratory control?
Arousal –> delayed development of serotonin RAS
- stimulated laryngeal chemoreceptors elicit INHIBITORY cardiorespiratory reflex
- prone position and respiratory tract infection in these children = FATAL
What are 3 exogenous stressors that inc. risk of SIDS?
hyperthermia, co-sleeping, sleeping on soft surfaces
What is a Hemangioma?
MOST COMMON TUMOR OF INFANCY
usually face and scalp = “port-wine stains”
- cavernous or capillary (capillary MORE cellular in children than adults = NO BUENO)
Lymphangiomas vs Lymphangiectasis
- angiomas: cystic/cavernous spaces
- usually deep regions of neck, axilla, retroperitoneal
- may encroach on vital tissue (fluid accumulation)
- angiectasis: abnormal dilation of preexisting channels
- diffuse swelling of all or part of EXTREMITY
- spongy/dilated subQ or deeper lymphatic ducts
What are Congenital-infantile Fibrosarcomas? What translocation is associated with them?
richly cellular and indistinguishable from adult versions
better outcome than adult = EXCELLENT prognosis
t(12;15) = ETV6-NTRK3 fusion transcript
- continually active RAS/PI3K/AKT pathways
- DIAGNOSTIC FINDING
Sturge-Weber Syndrome presentation and 4 associated factors (GLSS)
sporadic congenital neurocutaneous disorder
- “port-wine stain” in opthalamic branch of Trigeminal N.
- also: glaucoma, abnormal leptomeninges capillaries, seizures, stroke
What are Neuroblastomas and where are they found?
most common extracranial solid tumor of childhood
- diagnosis age = 18 months w/abdominal mass
- ALK mutation = familial predisposition to NB
location: adrenal medulla and sympathetic chain ganglia (Chromaffin cells)
- paravertebral region and post. mediastinum
Neuroblastomas and Pseudorosettes
rosettes where tumor are arranged concentrically around neuropil
- positive immunohistochemical reaction for ENOLASE
What is the relationship between Schwannian stroma and Ganglioneuroblastomas and Ganglioneuromas?
better outcome
- maturation of neuroblasts into ganglion cells usually accompanied by Schwann cells
Clinical Presentation of Neuroblastoma
large abdominal mass w/fever and weight loss
proptosis, “blueberry muffin baby” (disseminated neuroblastomas), bladder dysfunction
inc. serum catecholamines (VMA and HVA elevated)
What ages, stages, ploidy, and NMYC amplifications are associated with Favorable and Unfavorable prognosis for Neuroblastomas?
Favorable
- age: < 18 months
- stage: 1, 2a, 2b, 4s (commonly regresses on its own)
- ploidy: hyperdiploid
- NMYC amplification: NONE
Unfavorable:
- age: > 18 months
- stage: 3, 4
- ploidy: near diploid (chromothripsis)
- NMYC amplification: YES
use FISH analysis to find NMYC amplifications
What is Wilms Tumor? What do Nephrogenic Rests mean for Wilms Tumors?
most common renal tumor of childhood (age 2-5 and almost all by age 10)
Nephrogenic Rests: precursor lesions of Wilms tumor in RENAL PARENCHYMA
- pts @ inc. risk of developing Wilms tumor in other kidney –> SURVEILLANCE REQUIRED
WAGR Syndrome (Wilms Tumor)
- 33% w/Wilms Tumor, Aniridia, genital anomalies, MR
11p13 deletion (WT1 and Pax6 = aniridia (no iris))
**can have Pax 6 loss W/O WT1 loss
Denys-Drash Syndrome (Wilms Tumor)
- 90% w/Wilms Tumor, gonadal dysgenesis, early neuropathy
dominant (-) missense mutation in ZINC-FINGER region of WT1 protein (no DNA binding)
WT1 critical for kidney/gonad development (mutated = inc. risk of gonadoblastomas)
Beckwith-Wiedemann Syndrome (Wilms Tumor) and IGF-2/CDKN1C
- 5% w/Wilms Tumor, organomegaly, macroglossia, adrenal cytomegaly, omphalocele
involves 11p15.5 (WT2) –> Imprinting
- IGF-2 (paternal) –> uniparental disomy (tumor)
also CDKN1C –> p57 mutation
- inc. risk of hepato/pancreatoblastomas, rhabdomyosaracomas, and adrenocortical tumors
Wilms Tumor Morphology (4)
- large solitary well circumscribed mass (necrosis, cysts, hemorrhage)
- large abdominal mass across midline into pelvis (hematuria, bowel obstruction, hypertension)
Triphasic: blastemal (small blue cells), stromal, epithelial (tubules)
5% –> anaplasia (TP53 mutation)
