Red cell metabolism Flashcards
In order to fulfil its function, the red cell needs:
A supply of energy
A source of reducing power
Mature RBCs have no DNA, RNA or mitochondria
which means what type of glycolysis and what else
Anaerobic glycolysis
hexose monophosphate shunt and glutathione system
There is a lack of what synthesis in Mature RBC
Lack of protein synthesis
Mutations affecting RBC enzymes either effect what
catalytic activity or cause premature inactivation.
Glycolytic pathway =
glucose converted to pyruvate;
One mole glucose in the Glycolytic pathway =
two moles ATP;
What maintains intracellular cation balance
Na+ pumped out of RBC
K+ pumped into RBC
Membrane bound ATPase required
What maintains RBC cell shape
Failure of energy production = reduction of cell deformability and shape changes
Failure of Phosphorylation of glucose and fructose-6-phosphate prevents what
ATP production later in the pathway
Hexose Monophosphate Pathway also called
pentose phosphate pathway
Hexose monophosphate pathway consumes how much glucose - 5 - phospate
5-10%
Amount of Hexose monophosphate pathway consumed depends on
Amount depends on NAD+ and ATP availability
Glutathione cycle generates what
reducing power of the RBC via NADPH
Generates reducing power of the RBC via NADPH - (glutathione cycle) for:
Oxidation/peroxidation of membrane lipids increases rigidity Reduction of methaemoglobin
Generates reducing power of the RBC via NADPH - (glutathione cycle) for:
Reduction of methaemoglobin, how of occurs how often and reduces what
Occurs on a daily basis, reduces ferric to ferrous iron.
Generates reducing power of the RBC via NADPH - (glutathione cycle) for:
Detoxification of oxidants occurs during
During methaemoglobin formation, reactive oxygen species are developed – superoxide and hydroxyl radicals
2,3 DPG is formed from a
shunt involving 1,3 DPG, 3PG and DPG mutase
The synthesis of one mole 2,3 DPG inhibits
the production of one mole ATP
2,3 DPG inserts itself between
β-chains of deoxygenated Haemoglobin A
Hereditary red cell enzymopathies are
genetic disorders
enzymopathies cause hereditary
non-spherocytic haemolytic anaemias (HNSHA
Enzymopathies are associated with what type of cell
with normocytic normochromic red cells
Do enzymopathies have any
morphological characteristics
no
Most common enzymopathies deficiencies include:
Glucose-6-phosphate dehydrogenase (G6PD)
Pyruvate Kinase
The degree of haemolysis is enzymopathies is
variable.
Factors to consider in enzymopathies is
Which pathway has been affected?
What is the role of the enzyme?
What functional abnormalities have been introduced?
How easy is it for the individual to compensate for the haemolysis
Consequences of enzymopathies is
HNSHA Splenomegaly Jaundice Iron overload Non-haematological sequale
PKLR encodes PK for
(R)ed cells and (L)iver:
mutated PKLR / pyruvate kinase deficiency has the affect of
Reduced ATP production
Increased [2,3DPG]
varying clinical features of PK deficiency
Jaundice
Blood transfusion requirements (dependency in some)
Pigment gallstones
Extravascular haemolysis
Is there a link between residual PK activity and clinical severity.
NO
Red cells deficient in G6PD develop a secondary deficiency in
Glutathione.
X-linked condition
of G6DP linked too
Hemizygous in males
Variable presentation in females – Lyonisation
Enzymopathy diagnosis includes
FBC: NCNC anaemia Increased bilirubin Increased LDH Reduced haptoglobin Raised reticulocytes Exclude AIHA, membrane defects, haemoglobinopathies, enzyme investigations
G6PD deficiency is associated with a
loss of red cell reducing power and haemolytic anaemia
