Red Cell Enzyme defects

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Red Cell Enzyme defects

• ATP required for energy (pumps / glucose)
• 23 Diphosphoglycerate (23 DPG) required
• to regulate Hb/O2 dissociation
• Reduction mechanisms for oxidized
• Globin -- G6PD dependant system
• Haem -- Methhb. reductase

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Critical Enzymes/products

• G6PD
• MethHb Reductase
• Pyruvate Kinase
• 23 DPG

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G6PD Deficiency

• Globin spontaneously undergoes oxidation
• Oxidized globin unstable ?ppts
• 
  ?haemolysis
• Oxidation stresses
• eg. Naphthalene
• Nitrofuradantin
• Antimalarials
• Analgesics
• Infections

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G6PD deficiency

• Hexose monophosphate shunt products oxidation
  reduction
• G6PD key enzyme
• Deficiency leads to failure of reduction of
  oxydized globin
• G6PD def. is relative and is cell age dependent
• Older cells more sensitive to oxidant stress

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G6PD Deficiency

• Frequency
• Multiple varients
• 11 of American Negros
• Mediterranean 11000
• Jewish sect ---- 50

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G6PD Deficiency

• Inheritance
• X linked
• Lyon Hypothesis
• Random inactivation of
• X chromosome
• Expression
• Normal with level gt25
• Cong nonspherocytic Haem Anaemia
• Drug induced Haem Anaemia
• Favism

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Other Anaemias

• RBC Aplasia --- Acute/Chronic
• Aplastic Anaemia --- All involved
• 
  Idiopathic/2ary
• Renal failure
• Hypothyroidism
• Chronic disease

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Anaemia of Renal Failure

• Uremia --- Haemolysis
• Marrow supression
• Haemorrhage
• Reduced EPO
• Phosphate retention --- O2 diss curve