1. Hereditary Haemolytic Anaemias

2. Hereditary Haemolytic Anaemias
Look at the red cell as a floppy bag of haemoglobin
A floppy bag with three “bits”

3. Hereditary Haemolytic Anaemias
Look at the red cell as a floppy bag of haemoglobin
Membrane

4. Hereditary Haemolytic Anaemias
Look at the red cell as a floppy bag of haemoglobin
Membrane
Haemoglobin

5. Hereditary Haemolytic Anaemias
Look at the red cell as a floppy bag of haemoglobin
Membrane
Haemoglobin
Various chemicals

6. Hereditary malfunctions of the Hb molecule will be covered in other presentations

7. Membrane Malfunctions
Membrane malfunctions usually reduce the red cell’s flexibility.
Thus shortening red cell lifespan
Causing a haemolytic process

8. Membrane Malfunctions
e.g. hereditary spherocytosis
normal red cell
Spherocyte

9. Membrane Malfunctions
e.g. hereditary elliptocytosis
normal red cell
elliptocyte

10. Membrane Malfunctions
There is a (hereditary) problem with those proteins that give the red cell shape.
Spectrin
Ankryn
Proteins 3.1, 4, etc
Glycophorins
Reduced flexibility gives shortened cell lifespan
Hence a haemolytic process

11. Membrane Malfunctions
All membrane defects have varying clinical presentations
Some cause anaemias in the newborn
Some are chance findings in patients aged 80+ with chest infection
And there are cases in between the extremes

12. Acquired Membrane Malfunctions
Something usually overlooked
Stuff added to membrane
target cells in liver disease
Altered membrane permeability
burr cells in renal disease
physically damaged cells
schistocytes in H.U.S

13. The red cell membrane might be a floppy bag, but it’s important !

14. Red Cell Metabolism Remember !!!!!
Red cells have only those enzymes they were made with
can’t make more
Red cells are anaerobic
strange when you consider their function

15. Red Cell Metabolism Glucose goes in Hexokinase turns it to G-6-P
and then
Two main biochemical pathways

16. Red Cell Metabolism Glycolysis 2-3 diphosphoglycerate Pyruvate kinase
Pentose phosphate shunt
Glucose phosphate dehydrogenase
Though any enzyme may be deficient

17. Rappaport - lubering shuttle
Red Cell Metabolism
2-3 diphosphoglycerate
Glycolysis
Glucose :
1-3 DPG |
3 DPG
etc
Rappaport - lubering shuttle
DPG |
3 DPG :
etc

18. Red Cell Metabolism 2-3 diphosphoglycerate
“shifts the oxygen dissociation curve”
- what does that mean? -
2-3 DPG bonds deoxy-Hb avidly, thereby causing greater oxygen release to the tissues

19. without PK this don’t happen
Red Cell Metabolism
Pyruvate Kinase
Glycolysis
Glucose :
PEP |
Pyruvate + ATP
etc
without PK this don’t happen

20. Pentose phosphate shunt
Red Cell Metabolism
Glucose phosphate dehydrogenase
Pentose phosphate shunt
Glucose :
G6P |
6PG
etc
the etc includes production NADH and NADPH
which doesn’t happen if G6PD is lacking

21. Red Cell Metabolism
Glucose phosphate dehydrogenase & glutathione
Glutathione (GSH) is a protein which mops up oxidative substances in the red cell.
Glutathione reductase (GR) then recycles glutathione in a reaction that involves NAPD
2GSH + oxidative substance = GS-SG
GS-SG + GR +NADH = 2GSH
“oxidative substance” - what’s that then
Drugs, food, and anti-malarials !

22. Red Cell Metabolism To summarise: Membrane malfunctions HS HE Acquired
Enzyme deficiencies PK
G6PD
Haemoglobinopathies
later...