Approach to the yellow baby Flashcards
What are some of the functions of the liver?
Produces blood clotting enzymes
Absorption of foods (particularly fat)
Storage of glcogen (and albumin)
Metabolism and excretion of drugs and toxins
What is measured when doing liver function tests?
Bilirubin - total + split (conjugated + unconjugated)
ALT / AST
Alkaline phosphatase
Gamma glutamyl transferase (GGT)
What does raised ALT/AST indicate?
Hepatocellular damage
damage to hepatocytes - eg. in hepatitis
What do raised Alkaline phosphatase and Gamma glutamyl transferase (GGT) indicate?
Biliary disease
Since LFT’s are often more an indicator of damage of the liver rather than good function, what would you measure to test the function of the liver?
**Coagulation - PTT (prothrombin time), APTT
*Albumin
Bilirubin
Blood glucose / Ammonia
What is the cardinal sign of liver disease in children?
Jaundice
Additional symptoms of liver disease rarely seen without jaundice, otherwise liver disease mainly seen incidentally on tests
What are some features of liver disease in children that isn’t seen in adults?
Growth failure (failure to thrive)
What causes jaundice? Where is it most visible?
Buildup of bilirubin gives a yellow tinge, usually when bilirubin is above 40 umol/L
Most visible in sclera of eyes
Also seen if apply pressure and blanch the skin over the sternum (should go white, but is there a yellow tinge?)
What are the steps of bilirubin metabolism?
- Breakdown of erythrocytes into unconjugated bilirubin in RES and spleen
- Unconjugated bilirubin bound by albumin, transported to liver where glucuronic acid is added to make it conjugated bilirubin
- Conjugated bilirubin excreted in bile and converted to urobilinogen
- Urobilinogen either excreted in stool, by kidneys, or reabsorbed vie enterohepatic circulation and reincorporated into bile
Is bilirubin water soluble?
Unconjugated bilirubin is not water soluble, needs to bind albumin to be transported
Conjugated bilirubin is water soluble
What is raised unconjugated bilirubin a sign of?
Pre-hepatic jaundice
The problem lies with RBC metabolism and breakdown, making too much bilirubin to deal with
What is a mix of raised unconjugated and conjugated bilirubin a sign of?
Intrahepatic jaundice
Liver dysfunction is causing it to be unable to excrete bilirubin into the bile effectively, problem is with the liver
What is raised conjugated bilirubin a sign of?
Post-hepatic jaundice: cholestasis
Bilirubin is getting out of the liver and into the bile, but problems with biliary secretion are causing a buildup of conjugated bilirubin
What are the different age classifications for infant jaundice?
Early (< 24hrs)
Intermediate (24 hours - 2 weeks old)
Prolonged (> 2 weeks old)
If a baby is jaundiced at an early stage (< 24 hours old), what are the likely causes?
Always pathological**
- Haemolysis
- Sepsis
If a baby is jaundiced at an intermediate stage (24 hours - 2 weeks old), what are the likely causes?
Physiological
breast milk
- Sepsis
- Haemolysis
If a baby is jaundiced at an prolonged stage (> 2 weeks old), what are the likely causes?
Extrahepatic obstruction
Neonatal hepatitis
Hypothyroidism
Breast milk
What causes physiological jaundice in babies?
A misbalance in bilirubin metabolism is caused by:
- HbF having a shorter lifespan than adult Hb (haemolysis)
- Babies being relatively polycythaemic (high RBC)
- Their livers being relatively immature
Just means there will be high bilirubin for a bit that should resolve spontaneously as liver function catches up
In physiological jaundice, when does it develop? What type of bilirubin would be found mostly?
Develops after the first day of life
Mostly unconjugted bilirubin as excess haemolysis is uncompensated due to immature liver function
What is breast milk jaundice? What type of bilirubin is seen? How long does it last?
Jaundice that can be seen in breast fed infants that isn’t seen in bottle fed infants. Mechanism of jaundice is unclear.
Unconjugated bilirubin
Can last for around the first 3 months of life
What is kernicterus?
Serious complication of raised unconjugated bilirubin
Since unconjugated bilirubin is fat soluble it can cross the blood brain barrier, leads to toxic deposits of bilirubin in the brain (particularly basal ganglia)
What are some of the early signs of kernicterus?
Encephalopathy:
- poor feeding
- lethargy
- seizures
What are some of the late consequences of kernicterus?
Severe choreoathetoid cerebral palsy
Learning difficulties
Sensironeural deafness
How is raised unconjugated bilirubin treated in young babies?
Phototherapy
Placing the blidfolded baby under a 450nm wavelength (visible light - blue) converts unconjugated bilirubin to a water soluble isomer via photoisomerisation
(can also be done by exchange transfusion - more agressive: involves taking some of the babies blood and replacing it with other red cells)
What are some non-physiological causes of high unconjugated bilirubin in infants?
Sepsis
Haemolysis (ABO incompatibility, rhesus disease, bruising, red cell membrane defects)
Genetic:
- Gilbert’s disease (common, partial inability to conjugate bilirubin)
- Crigler Najjar syndrome (rare, near total inability to conjugate bilirubin)
What tests may be done in babies to find out or exclude non-physiological causes of high unconjugated bilirubin in babies?
Urine + blood cultures (sepsis)
Blood group + DCT (direct Coombs test) (haemolysis)
Blood film
Genetic testing
When is infant jaundice classified as being prolonged?
When it lasts for more than 2 weeks
More than 3 weeks in preterm babies
What are the main potential causes for prolonged jaundice in the infant?
Unconjugated:
- Breast milk
- Hypothyroidism
Conjugated:
- Neonatal hepatitis
- Biliary obstruction
What is the most important test to do on a baby that has jaundice?
A split bilirubin test
Conjugated bilirubin is ALWAYS pathological so knowing whether the bilirubin is conjugated is v important
What are the most important causes of biliary obstruction in young babies?
***Biliary atresia (bile can’t get out of liver - conjugated jaundice and pale stool)
Choledochal cyst (cystic malformation of bile duct, turbulent flow & blockage, conjugated jaundice and pale stool)
Allagile syndrome (intrahepatic blockage - genetic syndrome. comes with heart disease)
When an infant has prolonged jaundice what is the most important question in their history taking? What does it tell us?
Stool colour
If the stool is pale there is an obstruction that is stopping the passage of bile into the stool (biliary obstruction)
What is biliary atresia?
Congenital fibro-inflammatory disease of the bile ducts, starting at the extra-hepatic ducts and moving proximally
Causes obstruction of bile flow
How does biliary atresia present?
Jaundice
Pale stools
Dark urine
Progresses to liver failure if untreated
How is biliary atresia treated?
Kasai portoenterstomy
Remove the cystic ducts, anastamose the ileum onto the liver, anastamose the duodenum onto more distal ileum
Bile drains directly into gut afterwards. Ideally want to do the surgery before 9 weeks of age
Will eventually rely on liver transplant
What investigations can be done when there is suspected biliary obstruction?
Split bilirubin
Stool colour
USS
Liver biopsy
If the baby has prolonged conjugated jaundice, but no biliary atresia, what would be next in your DDx?
Neonatal hepatitis
What are some causes of neonatal hepatitis?
Alpha-1-antitrypsin deficiency Galactosaemia Tyrosinaemia Urea cycle defects Haemochromatosis Glycogen storage disorders Hypothyroidism Viral hepatitis Parenteral nutrition
