136 - Jaundice Flashcards
Where does jaundice first appear?
Sclera
Plasma bilirubin concentration must exceed for jaundice to be easily visible
35 micromolar
Synonym for jaundice
Icterus
Amount of bilirubin produced each day
4mg per kg
Which bilirubin is too high in indirect jaundice?
Unconjugated
Examples of pathologies that can lead to jaundice
Includes sepsis (especially cholangitis - infection of the common bile duct), biliary cirrhosis, pancreatitis, coagulopathy, renal and liver failure.
Protein that carries unconjugated bilirubin to ER in a hepatocyte
Ligandin
Pre-hepatic jaundice causes
Haemolyisis
Ineffective erythropoiesis
Post-hepatic jaundice causes
Gallstones
Biliary stricture
Carcinoma of pancreas of biliary tree
Cholangitis
Direct jaundice
High conjugated bilirubin
Hepatic jaundice
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)
Microsome
Artefact from a lab.
ER Doesn’t survive cell fractionation. Microsomes are clusters of what were once ER.
Splenic problem that can lead to haemolytic anaemia
Reticuloendothelial hyperactivity
Examples of bacterial toxins that can lead to haemolytic anaemia
Clostridial, streptococcal, meningococcal toxins
How can heart valves lead to haemolytic anaemia?
If there is a valvular problem, the valves can break red cells
March haemoglobinuria
Mechanical haemolytic anaemia.
From regular mechanical trauma (marching, running long distances, etc)
Normal blood [unconjugated bilirubin]
Under 20 micromolar/L
Lab findings in haemolytic jaundice 1 2 3 4 5 6
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
Number of neonates with jaundice
~1/3
Why does neonatal jaundice come about?
1
2
3
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
If neonatal jaundice persists for a few days, what could be causing it? 1 2 3 4 5 6
- Hemolytic disorders (ABO or Rh factor incompatibility)
- Glucose-6-phosphate dehydrogenase deficiency
- Birth trauma.
- Premature birth
- Breastfeeding
- Any condition casing hepatic inflammation.
How is jaundice level analysed?
Non-invasive spectal analysis.
Measures transcutaneous bilirubin value.
Generally accurate for levels up to 250 micromolar/L
Gilbert’s disease
Less-severe form of Crigler-Najjar.
Decreased conjugation of bilirubin and decreased uptake in some cases.
Often mild disease
Most common human enzyme deficiency
Glucose-6-phosphate dehydrogenase deficiency
What does glucose-6-phosphate dehydrogenase deficiency lead to?
Haemolytic anaemia
Distribution of glucose-6-phosphate dehydrogenase deficiency
Malaria areas. Haemolytic anaemia is an advantage for reducing malaria infection.
How does glucose-6-phosphate dehydrogenase deficiency confer resistance to malaria?
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
Glucose-6-phoasphate dehydrogenase function
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
Why does glucose-6-phosphate dehydrogenase deficiency affect RBCs and not other cells?
RBCs lack nucleus, can’t just make more glucose-6-phosphate dehydrogenase to compensate
Effect of glucose-6-phosphate dehydrogenase deficiency
Reduced glutathione.
Glutathione is made from pentose phosphate metabolism.
Cells are less able to protect themselves from ROS.
Function of pentose phosphate shunt
Produces NADPH, which helps form glutathione.
Glutathione protects against ROS.
What is chloroquine contraindicated in?
Glucose-6-phosphate dehydrogenase deficiency
Effect of choloquine on someone with GSH disease
Acute haemolysis
Classical feature of galactosaemia in neonates
Cataracts
Galactose
4-epimer of glucose.
How is galactose made?
Produced from glucose by epimerase.
Lactose
Glucose and galactose disaccharide
Effect of galactose-1-phosphate uridyltransferase deficiency
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.
Why can galactosaemia lead to cataracts?
Cataract formation is due to the osmotic effect of galactitol formed by aldehyde reductase.
