Haem and Haemoglobin

Question 1

In which cells are heme synthesised?
Which parts of the cells are responsible?

Answer 1

Erythroid cells in bone marrow, liver.
Mitochondria and cytosol.

Question 2

Which vitamin is required for heme synthesis, and with which enzyme is it associated?

Answer 2

Vitamin B6, associated with ALA synthase.

Question 3

Which enzyme in heme synthesis is inhibited by heavy metal ions?

Answer 3

ALA dehydratase, and Ferrochelatase.

Question 4

What are symptoms of porphobilinogen accumulation?

Answer 4

Abdominal pain, neuropsychiatric symptoms, urine that darkens on exposure.

Question 5

What is heme broken down into?

Answer 5

Heme –> Biliverdin –> Bilirubin.

Question 6

Outline the course of bilirubin in the body, from its origin from the breakdown of heme to its excretion.

Answer 6

Unconjugated bilirubin is bound to albumin in the blood. It is conjugated in the liver and taken into the bile caniculi via active transport. In the gut, bilirubin is converted to urobilinogen, which oxidises to form brown stercobilin. Some urobilinogen is reabsorbed into the portal circulation and resecreted, and the remainder is converted to urobilin in the kidneys and excreted.

Question 7

Classify jaundice and explain the difference between types of jaundice.

Answer 7

1. Prehepatic jaundice: caused by accumulation of bilirubin from rapid heme breakdown eg. hemolytic anemia
2. Hepatic jaundice: defect in conjugation or transport (excretion) eg. alcoholic liver disease/genetic conjugation defects
3. Obstructive jaundice: excretion of bilirubin as bile is blocked eg. bile duct stones/ neoplasias.

Question 8

Explain the pathophysiology of jaundice in mixed hepatocellular dysfunction

Answer 8

Early: defect in reabsorption (portal system) causing increase in conjugated bilirubin.
Late: defect in excretion predominates, worsening accumulation of conjugated bilirubin. Causes bilirubinemia.

Question 9

What are some biological markers for each of the three types of jaundice?

Answer 9

1. Prehepatic: decrease in haptoglobin (Free Hb binds to haptoglobin)
2. Hepatic: Increased AST/ALT, decrease in albumin, elevated PT/aPTT
3. Obstructive: increased ALP/GGT enzymes.

Question 10

Outline the changes in the predominant Hb type during embryogenesis.

Answer 10

Embryonic development: Hb Gower
Fetal development: HbF
After birth: HbA, less HbA2

Question 11

Patient presents with anemia, lab investigations show HbF and HbA2 levels are elevated. What is the likely etiology?

a. Alpha thalassemia
b. Beta thalassemia
c. Sickle-cell anemia
d. Hemophilia A

Answer 11

b. Beta thalassemia