Jaundice Flashcards
Jaundice in neonates can be split into 3 categories
1) Early (<24hrs old) = ALWAYS pathological
causes: haemolysis, sepsis
2) Intermediate (<2wks)
causes: physiological, breast milk, sepsis, haemolysis
3) Prolonged (>2wks old)
causes: extrahepatic obstruction, neonatal hepatitis, hypothyroidism, breast milk
(more likely to be pathological but could still be some physical causes eg breast milk jaundice extending into that time period)
What are the major causes of early/intermediate jaundice?
Physiological Jaundice Breast Milk Jaundice Sepsis Haemolysis Abnormal Conjugation (genetic problems)
All forms of Early/intermediate jaundice are unconjugated. What causes physiological jaundice?
Short RBC life span
Relative Polycythaemia
Immature Liver
What causes haemolysis in neonates?
ABO incompatible
Rhesus Disease
Spherocytosis
G6PD deficiency
What genetic causes can cause abnormal conjugation of bilirubin?
Gilbert’s Disease
Crigler-Najjar Syndrome
How do we test to determine the source of early/intermediate jaundice?
Split bilirubin, LFTs, Albumin, Coagulation tests, Glc & ammonia
Urine & blood cultures + TORCH screen (For sepsis)
Blood group, DCT, blood film & G6PD Assay (for haemolysis)
Genetic Testing
How do we manage early/intermediate jaundice?
Treat the cause
If really bad can do Blue Light phototherapy (only works for unconjugated jaundice)
The blue light converts bilirubin to a water soluble isomer
Kernicterus is a dangerous complication of unconjugated jaundice. What happens in it?
Unconjugated bilirubin is fat soluble
Crosses BBB
Deposited in brain (mostly basal ganglia)
Neurotoxic –> encephalopathy
How does kernicterus present?
Early –> Encephalopathy –> Poor feeding, lethargy & seizures
Late –> Cerebral palsy, LDs & SN deafness
What are the major causes of prolonged jaundice? (>2wks old, 3 if preterm)
Conjugated = Biliary Atresia (anatomical), Choledochal cyst, Alagille Syndrome or neonatal hepatitis
Unconjugated = Hypothyroid or breast milk jaundice
Assume Biliary Atresia until proven otherwise
What happens in Biliary Atresia?
Fibroinflammatory disease –> destruction of extrahepatic ducts
blocks flow of bile out liver (so conjugated) and don’t have pigment in stools so pale stools
starts more distally and then progresses proximally towards liver surface
Other signs include pale stool (chalky coloured), dark urine and liver failure if untreated
timely diagnosis -time to treatment determines prognosis
conjugated jaundice + pale stools
What happens in alagille syndrome?
Intrahepatic cholestasis (leading to conjugated jaundice), dysmorphism & congenital cardiac disease
What are some causes of neonatal hepatitis?
Viral Alpha-1-antitrypsin deficiency Haemochromatosis Parenteral Nutrition High ammonia etc etc
How do you test someone who presents with prolonged jaundice?
1st) Split bilirubin
2nd) Check stool colour
Other Tests:
- US for cysts & Atresia
- Liver biopsy for Atresia and some hepatitises
- Genotyping for Alagille Syndrome
- Specific tests for hepatitis causes e.g. serology, TFTs, A-1-A level, Ammonia & Fe studies
How do we treat Biliary Atresia after confirming it with US & biopsy?
Kasai Portoenterostomy
best result if performed before 60 days (<9 weeks)
success rate diminshes rapdily with age
What are the function of the liver?
Factory organ of the body – produces many of the important proteins and enzymes that body needs for day to day functioning of a variety of systems. One of the important groups pf proteins the liver produrces is clotting factors so in liver failure blood doesn’t clot as well
Absorptio, digestion and metabolism of almost all food types. Need bile to help absorb fat.
Storage organ for glycogen for glc storage, fat storage, storage of essential proteins such as labumin
Excretion and clearance of toxic susbtances from our body incl many drugs so these can build up if liver not working
What are the diff LFTs?
- bilirubin
Total
Split = direct (conjugated) + indirect (unconjugated)
ALT/AST
Alkaline phosphatase
GGT
But they don’t really tell u if liver functioning, they tell us if any damage of infl
When is ALT/AST elevated?
hepatocellular damage (hepatitis) ie damage to hepatocytes
When is alk phopshatase and GGT elevated?
biliary disease
If you truly want to measure the function of the liver what is the best test?
check coagulation - esp the PT or INR
What are the best tests to assess liver function?
Coagulation
Prothrombin time (PT)/INR
APTT
Albumin
Bilirubin
(Blood glucose)
(Ammonia)
As liver failure becomes more advanced end up getting hypoglycaemia and elevated ammonia (liver not clearing toxic metabolites effectively) but they tend to be later rather than early features of liver failure
So simplest measure of true liver function = measure clotting and take a look at the albumin as well
What are signs of chronic liver disease in children?
- jaundice (usually most obvious in sclera and usually visible when bilirubin >40-50 umol/l)
- growth failure
Pre-hepatic vs intrahepatic vs post-hepatic jaundice?
- pre-hepatic: problem before liver ie producing too mcuh bilirubin - mostly unconjugated. Haemolysis problem
- intra-heaptic = problem w liver itself so it’s not conjugating the bilirubin and if hold up in the liver with oedema and infl then not excreting it effectively. Usually due to liver disease. Mixed = unconjugated and conjugated
- post-hepatic = (cholestasis) - problem in bile getting out liver into small bowel to be exrceted - so tends to be an obstructive process. Mostly conjugated
What happens to bilirubin ie metabolism?
- in small intetsine, it’s converted to urobilinogen
- either rmeains in bowel and comes out as stercobilin in stool (gives faecal pigment)
- or reabsorbed from bowel and excreted by kidneys in urine
- or some reabsorbd urobilinogen from gut goes back to liver thro enteropheaptic circ and repeats cycle again
So what does the diagnosis of infant jaundice depend on?
Understanding bilirubin metabolism
Age of the infant
What is physiological juandice?
- shorter RBC lifespan in infants (80-90 days) (as neonates have mainly fetal rather than adult Hb)
- relative polycthaemia (high RCC)
- relative immaturity of liver function
=> increased red cell breakdown (haemolysis) and a liver not conjugating things as quickly as would in an older child or adult
- unconjugated jaundice
- develops after first day of life
What is breast milk jaundice?
Exact reason for prolongation of jaundice in breastfed infants unclear
Inhibition of UDP by progesterone metabolite?
Increased enterohepatic circulation?
Unconjugated jaundice
Can persist up to 12 weeks
A variant or closely linked condition to physiological jaundice
Breast fed infants more likely to become more jaundice than formula fed infants and that jaundice more likely to last longer than formula fed babies
Don’t know why this is – there is diff theories (enzyme that causes conjugation ie UDP is inhibited?, increase in enterohepatic circ so more absorption of bilirubin etc?)
Thoughts as to why we allow this to happen – protective effect against some infections in neonatal based??
What is a major complication of jaundice that we worry about?
kernicterus
What is kernicterus and what are the signs?
brain damage due to high bilirubin
Unconjugated bilirubin is fat-soluble (water insoluble) so can cross blood-brain barrier
Neurotoxic and deposits in brain
Early signs – encephalopathy – poor feeding, lethargy, seizures
Late consequences – severe choreoathetoid cerebral palsy, learning difficulties, sensorineural deafness
Can kernicterus occur with conjugated jaundice?
Kerniecterus can only occur with high levels of unconjugated jaundice, it doesn’t occur with with conjuugted juiandice (which tends to occur more in liver disease) as conjugated bilirubin can’t cross the BBB so doenst deposit in the brain and doesn’t cause kernicterus
What is the treatment for unconjugated jaundice?
phototherapy Visible light (450nm wavelength) (not UV) converts bilirubin to water soluble isomer (photoisomerisation)
Threshold for phototherapy in infants guided by charts
(avoid kernictuers)
What are other causes of early/intermediate unconjugated infant jaundice and what investigations would you do for them?
Sepsis (urine + blood cultures, TORCH screen)
Haemolysis
- ABO incompatibility (Blood group, DCT)
- Rhesus disease (Blood group, DCT)
- Bruising/cephalhaematoma (clinical examination)
- Red cell membrane defects (e.g. spherocytosis) (Blood film)
- Red cell enzyme defects (e.g. G6PD) (G6PD assay)
(Abnormal conjugation)
- Gilbert’s disease (genotype/phenotype)
- Crigler-Najjar syndrome (genotype/phenotype
most of infant jaundice is physiological
What is the key message abut conjugated prolonged jaundice and so what is the most important test in prolonged jaundice?
Conjugated jaundice in infants is always abnormal and always requires further investigation
The most important test in prolonged jaundice is a “split” bilirubin
(be more relaxed if unconjugated)
always assess stool colour in prolonged jaundice
Pale stools = some obstructive process going on to bile flow so pigment not getting into stool. Always abnormal and requires further investigation
if stool colour normal eg yellow, green or brown = can be quite relaxaed that have good bile flow
assessment of prolonged infant jaundice primarily targeted at diagnosing patients with biliary atresia early
What are the signs of choledochal cyst (causes biliary obstruction -> prolonged jaundice)?
conjugated jaundice
pale stools
What is the most common indication for liver transplant in children?
biliary atresia
What is Kasai protoenterostomy?
Surgical procedure where firbossed damaged bile ducts are removed
And surgeon resects small bowel, takes distal arm of small bowel up to liver surface and anastomoses that directly onto the liver surface so all the bile drains out from the liver directly into the small intestine.
And then attach the proximal arm of small bowel into the side of that loop of small bowel in a roux-en-y connection so get this direct driange of bile into the bowel restesablished with this connection
Best described as a palliative rather than a curative procedure as most infants whio had a kassai prpcedure will ultimately require a liver transplant at some point in their life but its much better if can get them thro as much of their life as poassible with own liver rather than a transplant and early Kasai gives them best chance of going that
What tests do you do for the different causes of biliary obstruction causing prolonged jaundice?
Biliary atresia
(split bilirubin, stool colour, ultrasound, liver biopsy)
Choledochal cyst
(split bilirubin, stool colour, ultrasound)
Alagille syndrome
(dysmorphism, genotype)
What are the causes of neonatal hepatitis causing prolonged jaundice and the tests you would do?
Alpha-1-antitrypsin deficiency (phenotype/level) Galactosaemia (GAL-1-PUT) Tyrosinaemia (amino acid profile) Urea cycle defects (ammonia) Haemochromatosis (iron studies, liver biopsy) Glycogen storage disorders (biopsy) Hypothyroidism (TFTs) Viral hepatitis (serology, PCR) Parenteral nutrition (history)
What should conjugated jaundice always be considered as until proven otherwise?
biliary atresia
