approach to the yellow baby

Question 1

what are the functions of the liver

Answer 1

• synthetic function: proteins, enzymes
  
  • e.g. clotting factors
• absorption and metabolism
  
  • bile for fat absorption; proteins and carbs
• storage
  
  • e.g. glycogen, fat, protein
• excretion and clearance of toxic products

Question 2

what 4 things are included in a LFT

Answer 2

actually assess liver damage

• bilirubin
  
  • total
  • split - direct (conjugated) and indirect (unconjugated)
• ALT/AST - alanine aminotransferase, aspartate aminotransferase
• alkaline phosphatase
• gamma glutamyl transferase (GGT)

Question 3

when would ALT/AST be elevated

Answer 3

hepatocellular damage - hepatitis

Question 4

when would alkaline phosphatase and gamma glutamyl transferase (GGT) be elevated

Answer 4

biliary disease

Question 5

tests to assess liver function

Answer 5

coagulation - prothrombin time (PT)/INR, APTT - liver’s production of clotting factors

albumin - synthetic function of liver

bilirubin - clearance of bile from liver

(blood glucose) - hypoglycaemia can be a clearance of liver failure

(ammonia) - can be elevated in liver failure

Question 6

clinical manifestations of paediatric liver disease

Answer 6

• jaundice
• incidental finding of abnormal blood test
• symptoms/signs of chronic liver disease

Question 7

signs of chronic liver disease in children

Answer 7

head: encephalopathy, epistaxis

skin: jaundice,spider naevi, bruising and petechia

portal HT: varices , splenomegaly

abdo: hypersplenism, hepatorenal failure, ascites

peripheral: liver palms, clubbing, peripheral neuropathy, hypotonia

malnutrition: muscle wasting, loss of fat stores, rickets 2y to vit D deficiency

cholestasis: fat malabosorption, deficiency of fat soluble vitamins, pruritis, pale stools, dark urine

growth failure

Question 8

what is jaundice

Answer 8

= yellow discolouration of skin and tissues due to accumulation of bilirubin

most common presentation of liver disease in children

usually most obvious in sclera, can also check when blanching skin (press finger over sternum and look at colour)

Question 9

when does jaundice become visible

Answer 9

usually visible when total bilirubin >40-50umol/l

Question 10

DDx for jaundice

Answer 10

beta-carotenaemia - high consumption of carotene high foods e.g. carrots

• yellow discolouration of sclera is more likely to be jaundice as beta-carotenaemia only discolours skin and slcera will remain white

Question 11

what is diagnosis of infant jaundice dependent on

Answer 11

• bilirubin metabolism
• age of infant

Question 12

describe the process of bilirubin metabolism

Answer 12

1. red cells reach end of their life and are ready to be broken down
2. Hb is broken down - iron recycled to make new Hb, haem portion is broken down to make biliverdin
3. free circulation biliverdin is converted by biliverdin reductase into unconjugated bilirubin
4. unconjugated bilirubin is bound to albumin and transported to the liver
5. in the liver is is conjugated w/ glucuronic acid bu UDP glucuronosyltransferase to make conjugated bilirubin
6. conjugated bilirubin is excreted from the liver into the bile and then through the bile duct into the small intestine
7. in the small intestine it is converted into urobilinogen which leaves in the stool as stercobilin (converted from urobilinogen by bacteria in the gut) or is excreted by the kidneys
8. some of the reabsorbed urobilinogen from the gut goes back through the liver via enteropathic circulation and repeats the cycle

Question 13

where are red cells broken down

Answer 13

reticular endothelial systems

• spleen

Question 14

is unconjugated bilirubin soluble

Answer 14

water insoluble - has to be transported bound to albumin

conjugated bilirubin is water soluble

Question 15

which part of bilirubin metabolism does pre-hepatic jaundice affect

Answer 15

• any cause of jaundice where the cause lies before the liver
• XS bilirubin production
• mostly unconjugated

Question 16

which part of bilirubin metabolism does intra-hepatic jaundice affect

Answer 16

• problem within the liver itself
• liver isn’t conjugating bilirubin as well as it should be
• not excreting bilirubin into the bile effectively
• mixed picture of elevated conjugated and unconjugated bilirubin

Question 17

which part of bilirubin metabolism does post-hepatic jaundice affect

Answer 17

aka cholestasis

• bile can’t get out of liver into small bowel to be excreted
• tends to be obstructive process, bilirubin is still getting to the liver and being conjugated but isn’t getting out
• elevation of conjugated jaundice

Question 18

when does early neonatal jaundice occur

Answer 18

early - <24hrs old

Question 19

causes of early neonatal jaundice

Answer 19

ALWAYS PATHOLOGICAL

haemolysis, sepsis

Question 20

when does intermediate neonatal jaundice occur

Answer 20

24hrs-2wks

Question 21

causes of intermediate neonatal jaundice

Answer 21

physiological

breast milk

sepsis

haemolysis

Question 22

when does prolonged neonatal sepsis occur

Answer 22

>2wks

• >3wks for preterm infants

Question 23

causes of prolonged neonatal sepsis

Answer 23

conjugated: extrahepatic obstruction - biliary obstruction, neonatal hepatitis
unconjugated: hypothyroidism, breast milk

Question 24

what is physiological jaundice

Answer 24

occurs after the first 24hrs

affects the vast majority of infants to some degree

Question 25

why does physiological jaundice occur

Answer 25

shorter RBC life span in infants - 80-90days relative polycythaemia (high RBC count) - typical Hb 180-200 relative immaturity of liver function * more RBC breakdown, liver isn't conjugating as quickly → jaundice **unconjugated jaundice, occurs AFTER first day of life**

Question 26

why does physiological jaundice occur after the first day of life

Answer 26

takes time for RBC to break down and jaundice to build up

Question 27

why does breast milk jaundice occur

Answer 27

exact reason for prolongation of jaundice in breastfed infants is unclear * ? inhibition of UDP by progesterone metabolite → less conjugation → increased unconjugated jaundice * ? increased enterohepatic circulation → more reabsorption of bilirubin → higher levels in bloodstream

Question 28

what is breast milk jaundice

Answer 28

jaundice is more likely in breastfed babies than formula fed **unconjugated jaundice** can persist up to 12wks

Question 29

why is jaundice important to investigate

Answer 29

kernicterus unconjugated bilirubin is fat soluble so can cross blood brain barrier neurotoxic and deposits in brain

Question 30

early signs of kernicterus

Answer 30

encephalopathy poor feeding lethargy seizures

Question 31

late consequences of kernicterus

Answer 31

serve choreioathetoid cerebral palsy learning difficulties sensorineural deafness

Question 32

what type of jaundice does kernicterus occur with

Answer 32

only high levels of unconjugated

Question 33

how to avoid kernicterus developing

Answer 33

phototherapy for unconjugated jaundice * visible light (450nm) wavelength, NOT UV, converts bilirubin to water soluble isomer (photoisomerisation) * threshold for phototherapy in infants guided by charts

Question 34

causes of haemolysis resulting in early/intermediate unconjugated infant jaundice

Answer 34

ABO incompatibility rhesus disease bruising/cephalhaematoma red cell membrane defects e.g spherocytosis red cell enzyme defects e.g. G6PD

Question 35

causes of abnormal conjugation resulting in early/intermediate unconjugated infant jaundice

Answer 35

Gilbert's disease - common, mild Crigler-Najjar syndrome - v. rare, severe, high rates of kernictus

Question 36

tests to exclude sepsis as a cause of jaundice

Answer 36

urine and blood cultures TORCH screen

Question 37

tests to exclude haemolysis as a cause of jaundice

Answer 37

ABO incompatibility, 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

Question 38

tests to exclude abnormal conjugation as a cause of jaundice

Answer 38

Gilbert's disease, Crigler-Najjar syndrome - genotype, phenotype

Question 39

prolonged jaundice - conjugated jaundice

Answer 39

conjugated jaundice in infants is **always** abnormal and **always** requires further investigation

Question 40

what is the most important test in prolonged jaundice

Answer 40

split bilirubin - determine whether it is conjugated or unconjugated

Question 41

causes of prolonged jaundice - biliary obstruction

Answer 41

**biliary atresia** - conjugated jaundice, pale stools **choledochal cyst** - conjugated jaundice, pale stools **alagille syndrome** - intrahepatic cholestasis, dysmorphism, congenital cardiac disease

Question 42

prolonged jaundice - stool colour

Answer 42

**always** assess stool colour * pale stools indicate obstructive process and pigment isn't getting into stool * normal stool colour (yellow/green/brown) - good bile flow is intact

Question 43

3 things to remember about prolonged jaundice

Answer 43

conjugated jaundice in infants is **always** abnormal and **always** requires further investigation **always** assess stool colour assessment of prolonged infant jaundice is primarily targeted at diagnosing patients with biliary atresia early

Question 44

what is biliary atresia

Answer 44

congenital fibro-inflammatory disease of bile ducts → destruction of extra hepatic bile ducts inflammation typically progresses proximally towards liver and leads to destruction of bile ducts

Question 45

presentation of biliary atresia

Answer 45

prolonged, conjugated jaundice pale stools, dark urine most common indication for liver transplantation in children

Question 46

why is it important to diagnose biliary atresia

Answer 46

progression to liver failure if not identified and treated timely diagnosis critical as time to treatment determines prognosis

Question 47

treatment for biliary atresia

Answer 47

Kasai portoenterostomy * fibrous bile ducts are removed * distal end of small bowel taken up to liver surface and anastomosis created onto liver surface * bile drains directly into small intestine from liver * proximal end of small bowel attached to loop of small bowel to re-establish connection

Question 48

prognosis following Kasai portoenterostomy

Answer 48

success rate diminishes rapidly w/ age best results if performed before 60 days (\<9wks) palliative rather than curative - will likely require liver transplant later in life

Question 49

investigations for biliary obstruction causes of prolonged jaundice

Answer 49

biliary atresia - split bilirubin, stool colour, US, liver biopsy choledocal cyst - split bilirubin, stool colour, US alagille syndrome - dysmorphism, genotype

Question 50

causes of prolonged jaundice - causes of neonatal hepatitis

Answer 50

alpha 1 antitrypsin deficiency galactosaemia tyrosinaemia urea cycle defects haemochromatosis glycogen storage disorders hypothyroidism viral hepatitis and other infectious causes - hep B/C, toxoplasma, CMV, EBV, UTI septicaemia, meningitis parenteral nutrition

Question 51

tests for causes of prolonged jaundice - causes of neonatal hepatitis

Answer 51

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 - hx