136 - Jaundice

Question 1

Where does jaundice first appear?

Answer 1

Sclera

Question 2

Plasma bilirubin concentration must exceed for jaundice to be easily visible

Answer 2

35 micromolar

Question 3

Synonym for jaundice

Answer 3

Icterus

Question 4

Amount of bilirubin produced each day

Answer 4

4mg per kg

Question 5

Which bilirubin is too high in indirect jaundice?

Answer 5

Unconjugated

Question 6

Examples of pathologies that can lead to jaundice

Answer 6

Includes sepsis (especially cholangitis - infection of the common bile duct), biliary cirrhosis, pancreatitis, coagulopathy, renal and liver failure.

Question 7

Protein that carries unconjugated bilirubin to ER in a hepatocyte

Answer 7

Ligandin

Question 8

Pre-hepatic jaundice causes

Answer 8

Haemolyisis

Ineffective erythropoiesis

Question 9

Post-hepatic jaundice causes

Answer 9

Gallstones
Biliary stricture
Carcinoma of pancreas of biliary tree
Cholangitis

Question 10

Direct jaundice

Answer 10

High conjugated bilirubin

Question 11

Hepatic jaundice

Answer 11

Pre-microsomal (EG: rifampicin)

Microsomal (EG: hepatitis viruses, Cirgler-Najjar syndrome, Gilbert’s syndrome)

Post-microsomal (EG: impaired excretion, EG hepatitis, drugs - rifampicin)

Intrahepatic obstruction (hepatitis, cirrhosis)

Question 12

Microsome

Answer 12

Artefact from a lab.

ER Doesn’t survive cell fractionation. Microsomes are clusters of what were once ER.

Question 13

Splenic problem that can lead to haemolytic anaemia

Answer 13

Reticuloendothelial hyperactivity

Question 14

Examples of bacterial toxins that can lead to haemolytic anaemia

Answer 14

Clostridial, streptococcal, meningococcal toxins

Question 15

How can heart valves lead to haemolytic anaemia?

Answer 15

If there is a valvular problem, the valves can break red cells

Question 16

March haemoglobinuria

Answer 16

Mechanical haemolytic anaemia.

From regular mechanical trauma (marching, running long distances, etc)

Question 17

Normal blood [unconjugated bilirubin]

Answer 17

Under 20 micromolar/L

Question 18

Lab findings in haemolytic jaundice 
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Answer 18

1) High plasma unconjugated bilirubin
2) Decreased plasma haptoglobins
3) Increased urine urobilinogen
4) Increased reticulocytes
5) Decreased haemoglobin
6) Possible evidence of haemolysis on blood film

Question 19

Number of neonates with jaundice

Answer 19

~1/3

Question 20

Why does neonatal jaundice come about?
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3

Answer 20

1) Increased haem catabolism (because changing from foetal haemoglobin to adult haemoglobin - decreased gamma, increased beta chain)
2) Immaturity of the liver in bilirubin conjugation and excretion
3) Newborn liver doesn’t produce adequate ligandin, gluconuryl transferase

Question 21

If neonatal jaundice persists for a few days, what could be causing it? 
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Answer 21

• Hemolytic disorders (ABO or Rh factor incompatibility)
• Glucose-6-phosphate dehydrogenase deficiency
• Birth trauma.
• Premature birth
• Breastfeeding
• Any condition casing hepatic inflammation.

Question 22

How is jaundice level analysed?

Answer 22

Non-invasive spectal analysis.
Measures transcutaneous bilirubin value.
Generally accurate for levels up to 250 micromolar/L

Question 23

Gilbert’s disease

Answer 23

Less-severe form of Crigler-Najjar.
Decreased conjugation of bilirubin and decreased uptake in some cases.
Often mild disease

Question 24

Most common human enzyme deficiency

Answer 24

Glucose-6-phosphate dehydrogenase deficiency

Question 25

What does glucose-6-phosphate dehydrogenase deficiency lead to?

Answer 25

Haemolytic anaemia

Question 26

Distribution of glucose-6-phosphate dehydrogenase deficiency

Answer 26

Malaria areas. Haemolytic anaemia is an advantage for reducing malaria infection.

Question 27

How does glucose-6-phosphate dehydrogenase deficiency confer resistance to malaria?

Answer 27

When malaria enters RBC, uses NADPH from host cell (As doesn’t produce it’s own).
If the cell is deficient in G6PD, it doesn’t have much NADPH as it can’t make it through the pentose phosphate shunt. If this is used by by malaria parasite, RBC lyses as can’t produce glutathione

Question 28

Glucose-6-phoasphate dehydrogenase function

Answer 28

Pentose phosphate step-1 is catalysed by glucose-6-phosphate dehydrogenase.
Glucose-6-phosphate taken from glycolysis, shunted into pentose phosphate pathway.

In glucose-6-phosphate dehydrogenase deficiency the enzyme has a short life and is depleted before the normal 120 day life of RBCs

Question 29

Why does glucose-6-phosphate dehydrogenase deficiency affect RBCs and not other cells?

Answer 29

RBCs lack nucleus, can’t just make more glucose-6-phosphate dehydrogenase to compensate

Question 30

Effect of glucose-6-phosphate dehydrogenase deficiency

Answer 30

Reduced glutathione.
Glutathione is made from pentose phosphate metabolism.
Cells are less able to protect themselves from ROS.

Question 31

Function of pentose phosphate shunt

Answer 31

Produces NADPH, which helps form glutathione.

Glutathione protects against ROS.

Question 32

What is chloroquine contraindicated in?

Answer 32

Glucose-6-phosphate dehydrogenase deficiency

Question 33

Effect of choloquine on someone with GSH disease

Answer 33

Acute haemolysis

Question 34

Classical feature of galactosaemia in neonates

Answer 34

Cataracts

Question 35

Galactose

Answer 35

4-epimer of glucose.

Question 36

How is galactose made?

Answer 36

Produced from glucose by epimerase.

Question 37

Lactose

Answer 37

Glucose and galactose disaccharide

Question 38

Effect of galactose-1-phosphate uridyltransferase deficiency

Answer 38

Galactosaemia.
Buildup of galactose, as can’t remove it from the blood by converting it to glucose.
Can lead to jaundice by damaging liver by blocking bile canaliculi.

Question 39

Why can galactosaemia lead to cataracts?

Answer 39

Cataract formation is due to the osmotic effect of galactitol formed by aldehyde reductase.