Tieman Brandau Neonatal Case Flashcards
Tests based on substances released from damaged tissue
endogenous substances released by damaged hepatocytes;
ALT
AST
Lactic dehydrogenase
Endogenous substances reflecting impaired bile flow: GGT Alk Phos 5'-nucleotidase Leucine aminopeptidase
Tests based on substances synthesized by teh liver
albumin coag factors serum lipids and lipoproteins triglycerides cholesterol
Cholestasis
Impaired bile flow caused by either intrahepatic or extrahepatic disorders
Laboratory studies will show increased direct bilirubin (conjugated bilirubin) measurements
Physiologic jaundice
defined as jaundice in an otherwise healthy infant
NOT physiologic if develops before 36 hours of age, persists beyond 10 days or if direct bilirubin is > 20 % of total bilirubin
Breast milk jaundice
Approximately 2% of breast fed infants will have prolonged unconjugated hyperbilirubinemia with levels ranging from 10-15 mg/dL
be wary of kernicterus
important test to get with infants
ammonia levels– important for inborn errors of metabolism
Differential Diagnosis for Neonatal Cholestasis
Infection
Metabolic disorders (20%)
Endocrine
Genetic (25%)
Familial intrahepatic cholestatic syndromes
Anatomical or obstructive disorders (25-35%)
Number of unique disorders causing cholestasis in the neonatal period is greater than in any other time of life
Infectious Causes of Neonatal Cholestasis
Viral-adenovirus, CMV, coxsackievirus, EBV, enterovirus, hepatitis A, B, C, herpes simplex, HIV, parvovirus, reovirus, rubella
Bacterial-UTI, sepsis, listerosis, TB
Spirochete-syphilis, leptospirosis
Parasites-toxoplasmosis, malaria, toxocariasis, histoplasmosis
congenital rubella syndrome- association
microcephaly
heart disease
petechiae and purpura
cataracts, glaucoma, strabismus, nystagmus, microphthalmia, iris dysplasia
early congenital syphilis
presents before 2 years
prematurity and intrauterine growth retardation
hepatosplenomegaly
nasal chondritis (snuffles)
skin rash
osteochondritis
neurological symptoms and signs, including hydrocephalus and cranial nerve palsies
late congenital syphilis
presentation after 2 years craniofacial malformation dental abnormalities interstitial keratitis deafness neurosyphilis paroxysmal cold haemoglobinuria
Toxoplasmosis
most common intrauterine infection in developing countries
affects more than one billion in the world
most common cause of posterior uveitis
Metabolic Causes of Neonatal Cholestasis
Galactosemia
Glycogen storage disease type 4
Fatty acid oxidation defects (SCAD, LCAD)
Urea cycle defects, arginase deficiency
Tyrosinemia
Lysosomal storage diseases (Gaucher, Farber Wolman and Niemann-Pick)
Galactosemia effects
brain damage cataracts jaundice enlarged liver kidney damage
if given milk, unmetabolized milk sugars build up and damage the liver, eyes, kidneys and brain
Glycogen storage disease Type IV
Andersen disease
autosomal recessive due to deficiency of glycogen banching enzyme
deficiency of GBE results in formation of an amylopectin-like compact glycogen molecule with fewer branching points and longer outer chains
patients with the classical form of GSDIV develop progressive liver disease early in life
the non-progressive hepatic variant of GSD IV is less frequent and these patients usually survive into adulthood
besides these liver related presentations, there are rare neuro muscular forms of GSD IV
Tyrosinemia 1 in Infants
Common Manifestations: Diarrhea and bloody stools
Vomiting
Poor weight gain
Extreme sleepiness
Irritability
“cabbage-like” odor to the skin or urine
Liver problems : Enlarged liver Jaundice Tendency to bleed and bruise easily Swelling of the legs and abdomen
Gaucher Disease Subtypes
get giant liver and spleen
Genetic Causes of Neonatal Cholestasis
Cystic fibrosis
Trisomy 13, 18 or 21
Turner syndrome
α-1 antitrypsin deficiency (10% of all causes of neonatal cholestasis)
Trisomy screening
21- down
18- edwards
13- patau
Turner syndrome
low posterior hairline webbed neck and extra skin wide-set nipples swollen hands discolored spots on skin swollen feet
Endocrine Causes of Neonatal Cholestasis
Hypothyroidism
Hypopituitarism
untreated congenital hypothyroidism
jaundice poor feeding hypotonia macroglossia large fontanelles, delayed closure course facial features mental retardation short stature
Familial Intrahepatic Cholestatic Syndromes
Alagille syndrome (arteriohepatic dysplasia)
Byler disease (Progressive Familial Intrahepatic Cholestasis)
Carioli disease
“Idiopathic” neonatal hepatitis
Alagille Syndrome
Autosomal dominant disorder Associated findings include: - Cholestatic liver disease - Pulmonary valvular stenosis or atresia - Vasuculopathy - Renal disease
3 most common forms of neonatal cholestasis
idiopathic neonatal hepatitis
extrahepatic biliary atresia
alpha-1-antitrypsin deficiency
when to do the Kasai procedure?
first 4 weeks of life
taking a loop of small bowel, putting it up into the porta hepatis, and hoping it will drain the bowel. This is all we had before liver transplants for babies came around.
CHOLESTASIS defn
The systemic retention of biliary constituents as a result of failure of formation and (or) the flow of bile
intrahepatic vs extrahepatic cholestasis
INTRAHEPATIC
Usually a failure of formation of bile at the hepatocyte level
Elevated transaminases and unconjugated bilirubin
Can also be an obstructive process confined to the intrahepatic bile ducts
EXTRAHEPATIC
Obstructive process of the extrahepatic bile ducts
Elevated AP, GGTP and conjugated bilirubin
NEONATAL OBSTRUCTIVE JAUNDICE - defn and most common causes
Must be considered in any newborn jaundice presenting or persisting after 14 days old
Elevated conjugated bilirubin, AP, GGTP
Often, but not always, with acholic stools
Most common causes are
Biliary atresia
Less common causes are congenital biliary tract anomalies, choledochal cysts, and infections
BILIARY ATRESIA
have a high index of suspicion
Post-natal destruction of EH bile ducts with resultant injury and fibrosis of IH bile ducts
Unknown etiology
~30% of neo-natal cholestatic jaundice
Females > males
Associated with extra-hepatic anomalies
Most common cause of hepatic death and reason for liver transplantation in children
Diagnosed by lab, US, MRC and liver bx
Treated by Porto-enterostomy (Kasai procedure)
Best results if done at < 60 days of age
If Kasai procedure fails, liver transplant
CHOLEDOCHAL CYSTS
Less common cause of pediatric obstructive jaundice (2-4%)
5 types—type V (intrahepatic) called Caroli’s disease***
60-70% are found at age under 10
- Present with obstructive jaundice, acholic stools, pruritis, abd. pain, and/or fever
- Diagnosed by typical lab pattern of obstructive jaundice, US, MRCP, and ERCP
- Should usually be surgically resected because of risk of malignancy and cholangitis
type 5 choledochal cysts
Caroli’s disease
