Approach to the Yellow Baby Flashcards
what are the functions of the liver?
Factory - produces many important proteins and enzymes for the body
Makes clotting factors – when liver not working your blood doesn’t clot as it should do
Liver play important role is absorption, digestion and metabolism of almost all food types we consume, you need bile to help you absorb fat and also plays essential role in digestion and absorption of fats, proteins and carbohydrates
storage organ for glycogen for glucose storage and for fat storage and some essential proteins like albumin
excretion and clearance of toxic products of our body, metabolism and excretion fo drugs and other toxic products to our body and if the liver fails we see a build up of toxic products in the body
Liver “function” tests (LFTs) - what are they?
(gorup of blood tests)
- Bilirubin - Total bilirubin and “Split” bilirubin – Direct (conjugated) + Indirect (unconjugated)
- ALT/AST (alanine aminotransferase/aspartate aminotransferase)
- Alkaline phosphatase
- Gamma glutamyl transferase (GGT)
LFTs dont tell you how well the liver in functioning but rather it is damaged
When do the following change:
- Bilirubin
- ALT/AST (alanine aminotransferase/aspartate aminotransferase)
- Alkaline phosphatase
- Gamma glutamyl transferase (GGT)
- Bilirubin - Bilirubin only goes up if damage
- ALT/AST (alanine aminotransferase/aspartate aminotransferase) - Elevated in hepatocellular damage (“hepatitis”)
- Alkaline phosphatase - Elevated in biliary disease
- Gamma glutamyl transferase (GGT) - Elevated in biliary disease
Tests to assess liver function how should it be done?
- Coagulation - Prothrombin time (PT)/INR and APTT
- Albumin - how liver is making protein
- Bilirubin
- (Blood glucose)
- (Ammonia)
If liver failure more advanced then you can get hypoglycaemia or elevated ammonia but tend to be later features of liver failure
Simplest measure of liver function if test clotting and look at albumin
What are the Clinical manifestations of paediatric liver disease?
- JAUNDICE - Most common presentation of liver disease in children is jaundice
- Incidental finding of abnormal blood test
- Symptoms/signs of chronic liver disease
what are the Signs of Chronic Liver Disease in Children?
+ Growth failure
Same as they are in adults
One that is different to adults is growth failure, FTF – not seen in adult patients
what is jaundice?
= yellow discolouration of skin and tissues due to accumulation of bilirubin
- Usually most obvious in sclera (Yellow of eye is true distinction for jaundice compared to other causes of yellow skin like eating lots of orange carrots (carotenemia))
- Usually visible when total bilirubin >40-50 umol/l
Diagnosis of infant jaundice dependent on what?
- Understanding bilirubin metabolism
- Age of the infant
Bilirubin metabolism - what is the process?
Starts with red cells that have reached end of life and broken down to be recycled by body
Broken down particularly in the spleen
Globin broken to amino acid
Iron reused to make new haem
Haem broken to biliverdin
Stercobilin gives stool its colour (faecal pigment)
Excreted in kidney in form of urine
Some goes back to liver
Pre-hepatic jaundice, Intrahepatic jaundice and Post-hepatic jaundice (cholestasis) - is bilirubin conjugated or not?
Pre-hepatic jaundice, Intrahepatic jaundice and Post-hepatic jaundice (cholestasis) jaundice - what are the causes?
Problem lies in the bile getting out of the liver into the small bowel to be excreted, tends to be an obstructive process
Pre-hepatic – cause of haemolysis and bilirubin production, making too much bilirubin
Hepatic – mixed picture due to liver disease, problem in liver, not conjugating it as much as it should do and also not excreting it into the bile effectively
Post-hepatic – cholestatic process which there is an obstructive process stopping bile getting out, Problem lies in the bile getting out of the liver into the small bowel to be excreted, tends to be an obstructive process
Understanding how bilirubin __________ and processed in body helps differentiate in the pathway where the body is coming from
metabolism
Neonatal jaundice – what are the different classifications by age?
Early (<24 hours old):
- Always pathological
- Causes: Haemolysis, Sepsis (infectious process)
-Intermediate (24hrs – 2 weeks) (most common)
•Causes: Physiological, Breast milk, Sepsis, Haemolysis
Prolonged (>2 weeks) (Prolonged most likely to be pathological rather that physiological)
•Causes: Extrahepatic obstruction, Neonatal hepatitis, Hypothyroidism, Breast milk
what is “Physiological” jaundice?
- Shorter RBC life span in infants (80-90 days)
- Relative polycythaemia (high total red cell count)
- Relative immaturity of liver function
- Unconjugated jaundice (Prehepatic jaundice)
- Develops after first day of life (Takes time for red cells to build up)
Excess red cell breakdown and immature liver function
what is Breast-milk jaundice?
- Exact reason for prolongation of jaundice in breastfed infants unclear
- Unconjugated jaundice
- Can persist up to 12 weeks
Closely linked to physiological jaundice
Breast fed infants more likely to be jaundice than formula fed
Why do we worry about assessing infants with jaundice?
Kernicterus
what is Kernicterus and what is the process causing it?
- Unconjugated bilirubin is fat-soluble (water insoluble) so can cross blood-brain barrier
- Neurotoxic and deposits in brain
Basal ganglia in brain
Avoidable condition
Can only occur with high levels of unconjugated jaundice, cant get it with conjugated jaundice as conjugated bilirubin cannot cross the BBB
whata re the consequences of Kernicterus?
- Early signs – encephalopathy – poor feeding, lethargy, seizures
- Late consequences – severe choreoathetoid cerebral palsy, learning difficulties, sensorineural deafness
Severe long term consequences
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
The way we avoid kernicterus developing
how is the treatment threshold of babies with neonatal jaundice decided?
Different charts based on gestation of baby
exchange transfusion – remove proportion of infants blood and replace with packed red cells and dilute the blood and take out the high levels of circulating bilirubin, more aggressive treatment
What are Other Causes of Early/Intermediate Unconjugated infant jaundice?
Sepsis (Any cause of infection)
Haemolysis
- ABO incompatibility (baby different blood group form mother)
- Rhesus disease (less common now due to rhesus screening)
- Bruising/cephalhaematoma
- Red cell membrane defects (e.g. spherocytosis)
- Red cell enzyme defects (e.g. G6PD)
(Abnormal conjugation)
- Gilbert’s disease – common, mild, slight reduction in function of UDP so less conjugation
- Crigler-Najjar syndrome – v. rare, severe (almost complete absence of UDP = Signiant impaired of conjugation of bilirubin)
Most infant jaundice is ________________
physiological/harmless
Other Causes of Early/Intermediate Unconjugated infant jaundice:
how do we exclude sepsis, haemolysis and abnornmal conjugation?
what is Prolonged infant jaundice?
- Jaundice persisting beyond 2 weeks of life
•3 weeks for preterm infants
what are the causes of Prolonged infant jaundice?
Conjugated:
- Anatomical (biliary obstruction)
- Neonatal hepatitis (liver inflammation)
Unconjugated:
- Hypothyroidism (causes reduction in conjugation)
- Breast-milk jaundice (jaundice may still be happening)
Prolonged jaundice key message number 1:
- _________ jaundice in infants is always ________ and always requires further ________
- The most important test in prolonged jaundice is a “_____” bilirubin (distinguish weather conjugated or unconjugated jaundice)
Conjugated
abnormal
investigation
split
what are the causes of prolonged jaundice – biliary obstruction?
(Stopping flow of bile out of liver)
- Biliary atresia - Conjugated jaundice, pale stools
- Choledochal cyst - Conjugated jaundice, pale stools
- Alagille syndrome - Intrahepatic cholestasis, dysmorphism, congenital cardiac disease
Prolonged jaundice key message number 2:
• Always assess _____ _____ in infants with prolonged jaundice
stool colour
Pale stool = some obstructive process going on stopping bile getting into stools
what is Biliary atresia?
Congenital fibro-inflammatory disease of bile ducts leading to destruction of extra-hepatic bile ducts
Progression to liver failure if not identified and treated
Timely diagnosis critical as time to treatment determines prognosis
Most common indication for liver transplantation in children
how does Biliary atresia present?
- Presents with prolonged, conjugated jaundice
- Pale stools, dark urine
Chalky colour stools, Obviously pale
Try see with your own eyes, e.g. photo of stool/nappy
Biliary atresia treatment - Kasai portoenterostomy
what is it?
Fibroses damaged bile ducts are removed and the surgeon dissects the small bowel and takes the distal arm of the small bowel and anastomoses it onto the liver surface so bile drains from liver directly into the small intestine and the proximal arm of the small bowel into the side of that loop of small bowel so you get direct drainage of bile into the bowel
Palliative rather that curative procedure and most will need a liver transplant
Prolonged jaundice key message number 3:
• Assessment of prolonged infant jaundice is primarily targeted at diagnosing patients with _______ ______ early
biliary atresia
So we can get them an early kasai procedure
Why we always check conjugated bilirubin and look at stool colour as beyond ever other diagnosis we want to find the children with biliary atresia early so we can get them an early surgical correction
Causes of prolonged jaundice – biliary obstruction
how do you check for each of the following?
- Biliary atresia
- Choledochal cyst
- Alagille syndrome
Alagille syndrome – look for other associated features like cardiac abnormalities and do some genetic testing for that
What are some causes of prolonged jaundice – neonatal hepatitis?
Group of conditions that cause liver inflammation
Prolonged conjugated jaundice and they don’t haver biliary atresia then think about these
Wide variety of causes
- Alpha-1-antitrypsin deficiency
- Galactosaemia
- Tyrosinaemia
- Urea cycle defects
- Haemochromatosis
- Glycogen storage disorders
- Hypothyroidism
- Viral hepatitis
- Parenteral nutrition
Causes of prolonged jaundice – how do you investigate for neonatal hepatitis?
Some key tests we would do to try and differentiate cause of hepatitis picture of jaundice
Conjugated jaundice without pale stools and no evidence of structural abnormality
More specialised area
Prolonged infant jaundice summary:
- Always ask about stool ______
- Most important test is a _____ bilirubin to differentiate unconjugated from conjugated jaundice
- Conjugated jaundice always requires further investigation and should be considered ______ _______ until proven otherwise
If unconjugated you can be more relaxed about it
colour
split
biliary atresia
