chemical pathology: heme synthesis

Question 1

Hemoglobin synthesis & breakdown pathway

Answer 1

diagram

Question 2

What is porphyrias

Answer 2

Autosomal dominant inherited defect of heme synthesis
Defect in one of 8 biochemical steps

Question 3

What is the two classifications of porphyrias

Answer 3

1. Porphyrinogens: oxidized to porphyrins reactive to UV light & transmit energy to oxygen & form oxygen radicals causing damage to skin (blisters, scars & hypertrichosis)
2. PBG & d-ALA: mimic neurotransmitters & severe CNS dysfunction causing acute attack

Question 4

What 3 events triggers an acute attack

Answer 4

When heme demand is high:
1. Onset after puberty (sex hormones activate)
2. Prolonged fasting/carbohydrate depletion
3. Drugs & alcohol (induce hepatic CYPP450 enzyme)

Question 5

What are the symptoms of acute attack

Answer 5

Abdominal pain: acute, diffuse, severe, radiating to pelvis & back
Sensory & motor neuropathy: weakness, bulbar palsy & respiratory paralysis
Autonomic neuropathy: tachycardia, hypertension & tachyarrhythmia
CNS: anxiety, psychosis & convulsions
Hyponatraemia: due to cerebral salt wasting

Question 6

How is acute attack diagnosed

Answer 6

PBG & d-ALA in urine

Question 7

What is the treatment for acute attack

Answer 7

Treat pain with opioids
Beta blockers for hypertensions
Diazepam/clonazepam for seizures
Reduce haem with glucose
Ascertain fluid balance & slowly correct hyponatremia
ICU for ventilator

Question 8

What is porphyria variegata

Answer 8

Afrikaner population with mutation in R59W in PPOX

Question 9

What is the symptoms of porphyria variegata

Answer 9

Chronic skin damage & acute attacks

Question 10

What does PPOX do

Answer 10

Facilitates reaction that happens in mitochondria & requires enzyme due to highly reduced environment

Question 11

How does the diagnosis of variegata porphyria consist of

Answer 11

South Africans with Afrikaner family history for mutation of R59W & plasma fluorescence scanning

Question 12

What does the diagnosis of porphyria consist of

Answer 12

Urine & EDTA blood (DNA, plasma fluorescence scanning & red cell porphyrins)

Question 13

What is the management of porphyria variegata

Answer 13

Skin damage (avoid sunlight & complete sunblock)
Venesection for PCT (reduce iron overload)
Blood transfusion for CEP
Medic alert for at risk patients
Comprehensive drug list for prescription

Question 14

What is the only autosomal recessive porhyria

Answer 14

Uroporphyrinogen deaminase