Lecture 15: Chemical-induced Methaemoglobin Flashcards
What form of iron is present in Methaemoglobin
Oxidised haem iron (Fe3+)
Why is methaemoglobin bad
oxidised haem iron cannot function as an oxygen-transporting pigment
What are the 3 mechanisms of haem iron oxidation
- Direct oxidation
- Indirect oxidation
- Oxidation following metabolic activation
What 3 factors are needed in a MetHB inducer in direct oxidation of haem iron
- Having a higher redox potential than Fe2+
- Able to penetrate RBC to access haemoglobin
- Capable of oxidation reactions in vivo
How do MetHB inducers cause damage in direct oxidation of haem iron
MetHB inducers cause direct oxidative damage to RBC membranes causing intravascular haemolysis
How does indirect haemoglobin oxidation occur
Hb-bound oxygen is reduced to water as it accepts electrons from haem iron and MetHB-forming species
How does oxidation via metabolic activation occur
Active metabolite enters an NADPH-dependent cycle of MetHB formation
What two mechanisms contribute to tissue hypoxia seen in methaemoglobinaemia
Direct and indirect oxidation
How does direct oxidation lead to tissue hypoxia
oxidised haem iron doesn’t bind to oxygen
How does indirect oxidation lead to tissue hypoxia
distortion of the haem tetramer means remaining iron atoms release oxygen less efficiently
Management of methaemoglobin poisoning
- remove skin exposure
- resuscitate
- methylene blue
