RBC Production and Survival

Question 1

what is the homeostasis mechanism of RBC production?

Answer 1

• stimulation: hypoxia due to low RBC count, Hb decrease or decrease in O2 availability
• decrease in [O2 blood]
• kidney (and liver to small extent) releases EPO
• EPO stimulates red bone marrow
• increase in erythropoiesis
• increase in O2 carrying ability of blood

Question 2

what other chemicals are released in RBC production?

Answer 2

-Fe, vitamin B12, folate, erythroid precursors released and produced

Question 3

where can Fe be found/obtained?

Answer 3

• sourced in meat, eggs, vegetables, dairy foods
• in normal western diet, absorption is 15mg daily
• regulated by DMT-1 and ferroportin

Question 4

what are the causes of Fe deficiency and what happens if there is a deficiency?

Answer 4

• decrease in uptake due to inadequate intake or malabsorption
• increase in demand during pregnancy or growth spurt
• increased loss of Fe due to a GI bleed or excess loss of blood in menses

-RBCs look like pencils in iron deficiency anaemia (IDA) which is the commonest form of anaemia where there is a decrease in Hb levels

Question 5

why is vitamin B12 and folate important for RBC production?

Answer 5

• essential for RBC maturation and DNA synthesis
• needed for the formation of thymidine triphosphate as B12 is a coenzyme for methionine synthase in the methylation of homocysteine
• deficiency in either can cause diminished and abnormal DNA

Question 6

what are the causes of VB12 deficiency?

Answer 6

• inadequate intake due to diet (veganism)
• absorption defect due to diseases like tropical sprue, coeliac dx, blind loop syndrome
• internal factor deficiency due to pernicious anaemia, Crohn’s disease or gastrectomy

Question 7

what are the causes of folate deficiency?

Answer 7

inadequate intake, absorption defect, increase in demand or drugs

Question 8

what is the cause of megablastic anaemia and what is used to treat it?

Answer 8

• due to B12 and folate deficiency

- patients administered folic acid, hydroxycobalamin

Question 9

what can also affect RBC production?

Answer 9

• renal disease: causes ineffective erythropoiesis

- decrease in BM erythroid cells: causes aplastic anaemia, marrow infiltration by leukaemia

Question 10

what are some stressors placed on RBCs?

Answer 10

• has a lifespan of 120 days
• travels 300m through microcirculation
• 8um in diameter
• has to fit in capillaries as small as 3.5um

Question 11

how are haemolytic anaemia classified?

Answer 11

• intrinsic vs extrinsic
• extracellular vs intracellular
• hereditary vs acquired

Question 12

what are the hereditary anaemias?

Answer 12

• red cell disorder: spherocytosis where RBC membrane integrity is lost and so the shape of the RBC is lost, and elliptocytosis where there are mutations in the horizontal interactions of the membrane proteins
• red cell enzymopathies: G6PD deficiency and PK deficiency
• haemoglobinopathies: SCD and thalassaemia

Question 13

how does G6PD deficiency cause anaemia?

Answer 13

• G6PD is involved in the pentose phosphate pathway where NADPH is produced
• NADPH is required to protect the RBC from oxidative damage
• G6PD is responsible for catalysis of the first step to producing NADPH
• NADPH produces reduced GSH which protects the RBC
• without G6PD, there is a decrease in NADPH and a decrease in GSH

Question 14

how does PK deficiency lead to anaemia?

Answer 14

-pyruvate kinase is required in glycolysis to produce ATP
-ATP is required to maintain RBC shape and deformability
and regulates [intracellular cation]
-when ATP is depleted, cell loses a large amount of K+ and H20 so cell becomes dehydrated and rigid
-this causes chronic non-spherocytic haemolytic anaemia
-can lead to jaundice and gall stones