L47- Pediatric Pathology III Flashcards
- (1) list types of neonatal jaundice
- (2) is the first physical exam sign used to determine jaundice in a newborn; once bilirubin levels reach (3)
1- physiological and pathological
2- blanching of skin with digital pressure
3- >5 mg/dl
describe process of physiological jaundice
(Note: cause is normal hemolytic activity)
-Defined as elevation of unconjugated bilirubin during 1st wk of life –> always starting from the 2nd day
Phase I: lasts 5 days (term infants) or 7 days (premature) – serum bilirubin ~12-15 mg/dl
Phase II: decline in bilirubin for 2 wks –> normal adult bilirubin values achieved
list the main features of pathological jaundice
-clinical jaundice appears w/in 24hrs of birth
Total Bilirubin: >15 mg/dl
Conjugated Bilirubin: >2 mg/dl
list the main examples for each type of pathological jaundice
Unconjugated:
- fetomaternal blood group incompatibility // hemolytic disease of newborn
- Crigler-Najjar syndrome Type I, II
Conjugates:
- biliary atresia
- neonatal hepatitis
- Dubin-Johnson syndrome
- Rotor syndrome
Erythroblastosis fetalis:
- (1) is the most extreme form of disease
- (2) is the classic form of disease in newborns
- death in utero = hydrops fetalis
- Kernicterus (via hyperbilirubinemia)
Hemolytic disease of the newborn, aka (1)- (2) describe pathogenesis
1- Erythroblastosis Fetalis
2:
- mother sensitization to fetal Ag via previous exposure (transfusion, previous birth)
- Ig against fetal RBC Ag produced –> crosses into placenta
- Ig attacks fetal RBCs in utero => hemolysis
describe the effects and results of in utero hemolysis (via erythroblastosis fetalis)
Anemia:
- extramedullary hematopoeisis (hepatosplenomegaly)
- cardiac decompensation (cardiac failure) –> hydrops (death)
Hb degradation –> inc bilirubin:
- jaundice
- kernicterus
discuss the important gross and microscopic findings seen on autopsy of Hydrops Fetalis (erythroblastosis fetalis)
- hepatosplenomegaly
- bile stained organs
- erythroblastic hyperplasia of BM
- extramedullary hematopoiesis in liver, spleen
Kernicterus is the result of high levels of (un-/conjugated) bilirubin [include bilibrubin values and solubility] crossing BBB because of (2) status of BBB. As a result, (3) change is noted in the brain, predominately in (4) area.
1- unconjugated bilirubin (lipid soluble – conjugated is water soluble) – at total bilirubin levels >20 mg/dl
2- BBB not as strong or resistant since its is still maturing
3- bile staining
4- basal ganglia, brainstem
describe phototherapy as a treatment for hyperbilirubinemia
- for elevated unconjugated bilirubin levels
- conjugates bilirubin from liposoluble form into water soluble form
- bilirubin excretion via urine
Crigler-Najjar Syndrome:
- (1) type inheritance pattern
- (2) is affected enzyme with (3) types of disease
1- AR
2- UDP-glucuronyltransferase
3:
- type I, complete absence of enzymatic activity
- type II, partial decrease in enzymatic activity
Type I Crigler-Najjar Syndrome:
- (complete/partial) loss of UDP-gluconyltransferase activity
- (2) resulting symptoms
- (3) Tx
1- complete loss
2- unconjugated hyperbilirubinemia –> bilirubin encephalopathy –> kernicterus –> most Pts die w/in 1yr
3- phototherapy
Type II Crigler-Najjar Syndrome:
- (complete/partial) loss of UDP-gluconyltransferase activity
- (2) resulting symptoms
- (3) Tx
1- partial loss
2- less severe form, jaundice may or may not be evident
3- Phenobarbital induces enzyme activity and upregulation + phototherapy
Embryonic / Fetal type biliary atresia:
- results from (1), associated with congenital (2)
- (3) is evident at birth, followed by (4)- include timeframe
1- aberrant intrauterine development of extraheptic biliary tree in utero
2- anomalies: malrotation of abdominal viscera, congenital heart disease
3- early onset neonatal cholestasis
4- jaundice free period after physiological jaundice period – 1wk
Perinatal type biliary atresia:
- (1) cause, w/o association with (2)
- (3) is evident at birth, followed by (4)- include timeframe
1- normal extra-hepatic biliary tree development (in utero) –> destroyed following birth via viral infection (or teratogen) –> bile duct resorption
2- congenital anomalies
3- normal fetus, jaundice free interval
4- late onset neonatal cholestasis (4-8 wks)
describe the morphology of the entire biliary tree in biliary atresia
Extrahepatic:
- inflammation and fibrosis of hepatic and common bile duct
- bile ductular proliferation
- portal tract edema, fibrosis
- parenchymal cholestasis
Intrahepatic:
- periductal inflammation
- progressive destruction of intrahepatic biliary tree
describe prognosis of biliary atresia
- 75% survival, operated w/in 60 days
- 20-30% survivial, operated w/in 90 days
-80% survival with transplantation
Idiopathic neonatal hepatitis:
- (1)% of neonatal hepatitis cases
- important to rule out (2) factors (secondary causes)
- affects (males/females) more
1- 10-15%
2- AAT-deficiency, extrahepatic biliary atresia, infectious agents
3- males, 2:1
describe microscopic features of idiopathic neonatal hepatitis
-hepatocytes form multi-nucleated Giant cells, diffusely distributed and prominent
- ballooning of cells
- acidophilic / eosinophilic degeneration
- cholestasis
Rotor Syndrome = (1):
- results from (2) defect
- (3) clinical presentation
- (4) microscopic presenatation
1- familial conjugated hyperbilirubinemia
2- defect of excretion of bilirubin into bile canaliculi from hepatocytes –> reabsorbed in blood
3: (mild symptomatic jaundice)
- jaundice
- intermittent attacks of epigastric discomfort
- occasional abdominal pain and fever
4:
- low grade pigment deposition
- dissociation of liver cells
- occasional necrotic foci
- fibrin precipitation
Dubin-Johnson syndrome:
- (1) type of inheritance pattern of (2) defect
- (3) is another associated defect
1- AR
2- defective transport of conjugated bilirubin out of hepatocytes into canalicular lumen
3- hepatic excretion of coproporyphrins (=> black liver appearance)
discuss the general characterization and diagnosis of Dubin-Johnson syndrome (include clinical features)
-chronic or intermittent jaundice with ‘black liver’ (coproporyphrin lysosomal accumulation)
- most patients are asymptomatic beyond mild, intermittent jaundice
- usually diagnosed in teenage or young adulthood age, few may be evident in neonates
Serum Bilirubin ~2-5 mg/dl
Cystic Fibrosis:
- (1) type of inheritance pattern for (2- most common) mutation of (3) gene on chromosome (4)
- (5) describe normal function of (3) protein
1- AR
2- ΔF508 deletion (70%, 3 base pair deletion) or one of 800 other mutations
3- CF transmembrane conductance receptor (CFTR)
4- chr.7
5- CFTR phosphorylated by protein kinase A via cAMP –> Cl- APC transporter (influx and efflux) in apical membranes, eccrine glands
CF:
- (1) describe changes seen in sweat gland
- (2) changes in bronchi / bronchioles
1:
- Normal: Cl- influx from duct lumen via CFTR drives Na+ resorption
- CF: inc [Cl-], [Na+] in sweat (less influx)
2:
- Normal: Cl- efflux into respiratory lumen balances / limits Na+, H2O influx/resorption to maintain mucosal hydration
- CF: no Cl- efflux –> massive Na+, H2O influx => mucosal dehydration
