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Title: The permeability of the red cell membrane
Author: Bawazir, Waleed Mohammed
ISNI:       0000 0004 5914 6645
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2015
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The red blood cell (RBC) has a small diffusional permeability to monovalent cations that is increased in some conditions exceeding the corrective ability of the NaKA TPase and affecting RBC hydration and shape. We investigated the molecular basis of three such conditions, distal renal tubular acidosis (dRTA), dehydrated stomatocytosis (OHSt), and familial pseudohyperkalaemia (FP). A family from South East India with dRTA and hereditary spherocytosis (HS) was studied . We found the severely affected children were homozygous for the mutation A8580 in band 3 whereas the asymptomatic parents were heterozygotes. Blood films from the children showed predominantly spherocytes and echinocytes. We investigated the genetic basis of pedigrees with OHSt or FP and found mutations in PIEZ01 and ABCB6 respectively. Protein analysis suggested that both mutant proteins were expressed and may associate in separate RBC membrane complexes. The expression of ABCB6 during erythropoiesis was also studied in FP-Cardiff and controls. FP-Cardiff, associated with the mutation R723Q in ABCB6, was asymptomatic at physiologic temperature however the RBCs leaked cations 4-6 times normal when refrigerated. The R723Q mutation has complete genetic penetrance and may have a frequency of 1 in 500 in the UK population. Build up of potassium in RBC units is a problem of blood storage. We found that two FPCardiff RBC units rapidly developed unacceptably high potassium levels when stored at 4 DC. This rapid loss of potassium could not be reversed by rejuvenating the stored FP RBCs, although rejuvenation replenished the ATP and 2,3-0PG levels in FP-Cardiff and controls. Levels of microvesicies in one FP unit was five times normal. Taken together, our data suggests that stored FP-Cardiff RBCs may be unsuitable for transfusion , a larger scale analysis of the storage properties of FP-Cardiff RBCs, and the development of DNA test to screen all blood donors for this condition are needed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available