Approach to the yellow baby

Question 1

What are some of the functions of the liver?

Answer 1

Produces blood clotting enzymes

Absorption of foods (particularly fat)

Storage of glcogen (and albumin)

Metabolism and excretion of drugs and toxins

Question 2

What is measured when doing liver function tests?

Answer 2

Bilirubin - total + split (conjugated + unconjugated)

ALT / AST

Alkaline phosphatase

Gamma glutamyl transferase (GGT)

Question 3

What does raised ALT/AST indicate?

Answer 3

Hepatocellular damage

damage to hepatocytes - eg. in hepatitis

Question 4

What do raised Alkaline phosphatase and Gamma glutamyl transferase (GGT) indicate?

Answer 4

Biliary disease

Question 5

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?

Answer 5

**Coagulation - PTT (prothrombin time), APTT

*Albumin

Bilirubin

Blood glucose / Ammonia

Question 6

What is the cardinal sign of liver disease in children?

Answer 6

Jaundice

Additional symptoms of liver disease rarely seen without jaundice, otherwise liver disease mainly seen incidentally on tests

Question 7

What are some features of liver disease in children that isn’t seen in adults?

Answer 7

Growth failure (failure to thrive)

Question 8

What causes jaundice? Where is it most visible?

Answer 8

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?)

Question 9

What are the steps of bilirubin metabolism?

Answer 9

1. Breakdown of erythrocytes into unconjugated bilirubin in RES and spleen
2. Unconjugated bilirubin bound by albumin, transported to liver where glucuronic acid is added to make it conjugated bilirubin
3. Conjugated bilirubin excreted in bile and converted to urobilinogen
4. Urobilinogen either excreted in stool, by kidneys, or reabsorbed vie enterohepatic circulation and reincorporated into bile

Question 10

Is bilirubin water soluble?

Answer 10

Unconjugated bilirubin is not water soluble, needs to bind albumin to be transported

Conjugated bilirubin is water soluble

Question 11

What is raised unconjugated bilirubin a sign of?

Answer 11

Pre-hepatic jaundice

The problem lies with RBC metabolism and breakdown, making too much bilirubin to deal with

Question 12

What is a mix of raised unconjugated and conjugated bilirubin a sign of?

Answer 12

Intrahepatic jaundice

Liver dysfunction is causing it to be unable to excrete bilirubin into the bile effectively, problem is with the liver

Question 13

What is raised conjugated bilirubin a sign of?

Answer 13

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

Question 14

What are the different age classifications for infant jaundice?

Answer 14

Early (< 24hrs)

Intermediate (24 hours - 2 weeks old)

Prolonged (> 2 weeks old)

Question 15

If a baby is jaundiced at an early stage (< 24 hours old), what are the likely causes?

Answer 15

Always pathological**

• Haemolysis
• Sepsis

Question 16

If a baby is jaundiced at an intermediate stage (24 hours - 2 weeks old), what are the likely causes?

Answer 16

Physiological
breast milk

• Sepsis
• Haemolysis

Question 17

If a baby is jaundiced at an prolonged stage (> 2 weeks old), what are the likely causes?

Answer 17

Extrahepatic obstruction
Neonatal hepatitis
Hypothyroidism

Breast milk

Question 18

What causes physiological jaundice in babies?

Answer 18

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

Question 19

In physiological jaundice, when does it develop? What type of bilirubin would be found mostly?

Answer 19

Develops after the first day of life

Mostly unconjugted bilirubin as excess haemolysis is uncompensated due to immature liver function

Question 20

What is breast milk jaundice? What type of bilirubin is seen? How long does it last?

Answer 20

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

Question 21

What is kernicterus?

Answer 21

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)

Question 22

What are some of the early signs of kernicterus?

Answer 22

Encephalopathy:

• poor feeding
• lethargy
• seizures

Question 23

What are some of the late consequences of kernicterus?

Answer 23

Severe choreoathetoid cerebral palsy

Learning difficulties

Sensironeural deafness

Question 24

How is raised unconjugated bilirubin treated in young babies?

Answer 24

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)

Question 25

What are some non-physiological causes of high unconjugated bilirubin in infants?

Answer 25

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)

Question 26

What tests may be done in babies to find out or exclude non-physiological causes of high unconjugated bilirubin in babies?

Answer 26

Urine + blood cultures (sepsis) Blood group + DCT (direct Coombs test) (haemolysis) Blood film Genetic testing

Question 27

When is infant jaundice classified as being prolonged?

Answer 27

When it lasts for more than 2 weeks More than 3 weeks in preterm babies

Question 28

What are the main potential causes for prolonged jaundice in the infant?

Answer 28

Unconjugated: - Breast milk - Hypothyroidism Conjugated: - Neonatal hepatitis - Biliary obstruction

Question 29

What is the most important test to do on a baby that has jaundice?

Answer 29

A split bilirubin test Conjugated bilirubin is ALWAYS pathological so knowing whether the bilirubin is conjugated is v important

Question 30

What are the most important causes of biliary obstruction in young babies?

Answer 30

***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)

Question 31

When an infant has prolonged jaundice what is the most important question in their history taking? What does it tell us?

Answer 31

Stool colour If the stool is pale there is an obstruction that is stopping the passage of bile into the stool (biliary obstruction)

Question 32

What is biliary atresia?

Answer 32

Congenital fibro-inflammatory disease of the bile ducts, starting at the extra-hepatic ducts and moving proximally Causes obstruction of bile flow

Question 33

How does biliary atresia present?

Answer 33

Jaundice Pale stools Dark urine Progresses to liver failure if untreated

Question 34

How is biliary atresia treated?

Answer 34

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

Question 35

What investigations can be done when there is suspected biliary obstruction?

Answer 35

Split bilirubin Stool colour USS Liver biopsy

Question 36

If the baby has prolonged conjugated jaundice, but no biliary atresia, what would be next in your DDx?

Answer 36

Neonatal hepatitis

Question 37

What are some causes of neonatal hepatitis?

Answer 37

``` Alpha-1-antitrypsin deficiency Galactosaemia Tyrosinaemia Urea cycle defects Haemochromatosis Glycogen storage disorders Hypothyroidism Viral hepatitis Parenteral nutrition ```