RED BLOOD CELL ENZYMOPATHIES (G6PD DEFICIENCY) Flashcards
Characteristics of rbc
7-8μm in diameter
•Flexible biconcave
•Disc shaped
•Anuclear
•Central area of pallor
•Contains haemoglobin responsible for gaseous exchange in tissues
•Has to travel round the body to achieve this function
•One trip round the whole body takes 20 seconds; in 120 days, it covers about 480km.
For the rbc to fulfill its function what must it do?
To fulfil these functions, it has to generate energy in form of ATP
•It also has to generate reducing power in form of:
➢Reduced Nicotinamide Adenine Dinucleotide (NADH) and
➢Reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH)
What is RED CELL METABOLISM?
The process of generating energy and reducing power constitutes RED CELL METABOLISM
What are RED CELL ENZYMOPATHIES?
Absence of specific enzymes in this metabolic process gives rise to
RED CELL ENZYMOPATHIES
What is the main biochemical pathway in red cell metabolism?
THE EMBDEN-MEYERHOF PATHWAY
This pathway comprises a series of biochemical reactions that converts glucose to lactate.
• In the process, ATP and NADH are generated.
What are the 2 side arms (shunts) of the Embden-Meyerhof pathway?
And what do they generate/ produce?
The Embden-Meyerhof pathway has TWO side arms (shunts):
➢The Luebering-Rapoport shunt
➢The Hexose monophosphate (or Pentose Phosphate) shunt
•The Luebering-Rapoport shunt generates 2,3 Diphosphoglycerate (2,3 DPG)
•The Hexose monophosphate shunt generates NADPH.
What is the function of ATP?
ATP: Energy to maintain red cell volume, shape and flexibility
What is the function of NADH?
NADH: Needed by methaemoglobin reductase to convert methaemoglobin (Fe3+) to functionally active haemoglobin (Fe2+)
What is the function of 2,3-DPG?
2,3-DPG: Regulation of haemoglobin’s oxygen affinity
What are the types of ENZYMOPATHIES?
•Glucose-6-Phosphate Dehydrogenase deficiency
•Pyruvate kinase deficiency
•Glutathione deficiency
What is GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY?
What is it’s classification?
•One of the most common enzymopathies due to deficiency of the enzyme glucose-6-phosphate dehydrogenase leading to intravascular haemolysis.
•Has a worldwide prevalence
Can be classified based on two (2) factors:
1. Type: Type A (Africans), Type B (Western world)
2. Severity:
➢Mild – Black Africans
➢Moderate – Middle East and South East Asia
➢Severe – Mediterranean countries
What is GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY aetiology?
Infections and other acute illnesses (e.g. diabetic
ketoacidosis
Drugs
Antimalarials (e.g. primaquine, pamaquine, chloroquine, Fansidar, Maloprim)
Sulphonamides and sulphones (e.g. co-trimoxazole, sulfanilamide, dapsone, sufasalazine)
Other antibacterial agents (e.g. nitrofurans, chloramphenicol)
Analgesics (e.g. aspirin), moderate doses are safe
Antihelminths (e.g. B-naphthol, stibophen)
Miscellaneous (e.g. vitamin K analogues, naphthalene (mothballs), probenecid)
Fava beans (possibly other vegetables)
What are the Clinical Features of G6PD DEFICIENCY?
•Usually manifests as attacks of haemolysis.
•In between attacks, the patient is ASYMPTOMATIC.
•The haemolysis is intravascular
•During attacks, patients present with:
•Symptoms and signs of anaemia
•Jaundice
•Dark coloured urine (haemoglobinuria)
What are the Investigations G6PD DEFICIENCY?
•Full blood count and differentials - ↓PCV
•Reticulocyte count –
•Blood film (normal stain) – Fragmented cells, bite cells, blister cells
•Blood film (supravital stain) – Heinz bodies (oxidized, denatured haemoglobin)
•Direct Coomb’s test: Negative
•Urinalysis: Haemoglobinuria, Haemosiderinuria.
•G6PD enzyme assay: Enzyme levels usually NORMAL (false normal) during attacks and LOW in-between attacks.
What is the treatment of G6PD DEFICIENCY?
•Stop the offending drug
•Treat infection if present
•Intravenous fluid rehydration to maintain high urine output
•Blood transfusion for severe or symptomatic anaemia
•In neonates: Phototherapy or Exchange Blood Transfusion
