Hereditary Haemolytic Anaemias

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Red Cell Metabolism Glycolysis 2-3 diphosphoglycerate Pyruvate kinase Pentose phosphate shunt Glucose - 6 - phosphate dehydrogenase Though any enzyme may be deficient

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

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

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

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

Red Cell Metabolism Glucose - 6 - 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 !

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