RBC production and Survival Flashcards
What factors affect erythropoiesis?
Eryhtropoietin Iron Vit B12 Folate Eryhtroid precursors
What treatment options are available for deficiencies in B12 & folate?
*B12 - Hydroxycobalamin 1mg im
Folate - Folic acid 5mg a day orally
*Hydroxycobalamin = injectible form of B12 given when B12 absorption problems in gut
B12 absorption involves IF made by gastric parietal cells.
TCI is secreted to prevent damage by salivary glands, protecing B12 from degradation
Why does erythropoiesis occur?
Stimulated by hypoxia due to
- Decreased RBC count
- Decreased Hb
- Decreased O2 availability
What pathological factors is RBC production effected by?
- Renal disease causes ineffective erythropoiesis
- Reduced bone marrow erythroid cells causes aplastic
anaemia and marrow infiltration by leukemia or other
malignancies
How is Iron obtained in the body?
Obtained via diet in meat, eggs, vegetables & dairy foods
5-10% absorbed (1mg) in duodenum and jejunum
Gastric secretion of HCl and absorbic acid aid absorption
What are the different types of hereditary hemolytic anemia?
Hameoglobinopathies
- Sickle cell diseases
- Thalassemias
RBC enzymopathies
- G6PD deficiency
- PK deficiency
RBC Membrane disorders
- Hereditary spherocytosis
- Hereditary ellipocytosis
Describe the blood oxygen levels during homeostasis
Blood oxygen levels are normal
Describe Hereditary spherocytosis
Loss of membrane integrity - RBC becomes spherical
due to deficiency in proteins with vertical interactions between membrane skeleton and lipid bilayer
What are the causes of folate deficiency?
Inadequate intake
- Poor nutrition
Absorption defects
- coeliac disease
- Crohn’s dx
- Tropical Sprue
Increased demands/losses
- Pregnancy
- Haemolysis
- Cancer
Drugs
- anticonvulsants
What is the significance of the glycolytic pathway?
Glycolytic pathway generates ATP
- to maintain RBC shape and deformabilty
- Regulates intracellular [cation] via Na+/K+ pump
What are the consequences of Pk deficiency?
PK deficiency is autosomal recessive
=> causes build up of glycolytic intermediates
(2,3-biphosphoglycerate which shifts oxygen diss.
curve to right) -> low O2 affinity
=> low intracellular ATP generation
affects membrane structure causing RBCs to have
arrowheads (irregularly contracted cells)
Outline the process of erythropoiesis due to hypoxia
- O2 levels reduced in blood
- Kidney (and liver) release EPO hormone
- Erythropoietin stimulates red bone marrow
- Enhanced erythropoiesis increases RBC count
- Increases O2 carrying ability of blood
How does the body destroy its own RBCs in AIHA?
AIHA anemic Red cells are coated with IgG alone or with a compliment enabling them to be taken up by rectoendothelial macrophages for degradation
How is folate transported around the body?
Folate weakly binds to albumin transport protein
What is the evolutionary benefit of acute hemolysis?
G6PD deficiency is X linked
Pateints with G6PD deficiency have to avoid particular oxidative drugs
- (quinone based anti malaria drugs)
When G6PD deficiency is treated with primaquine leads to a mild/severe acute hemolytic anemia
stimulating H2O2 production
Providing protection against severe anemia
What are the causes of iron deficiency?
Decreased uptake
- inadequate uptake
- malabsorption
Increased demand
- pregnancy
- growth spurt
Increased loss
- GI bleed
- Excess loss in menses
What are the consequences of RBC integral proteins defetcs?
Defects in Ankyrin, Spectrin, Band 3 or protein 4.2 leads to destabilisation of the overlying lipid bilayer and release of lipids into microvesicles
Causes hereditary elipocytosis
How does a PK deficiency cause mishapen RBCs?
ATP is depleted so cells lose large amounts of K+ & water
Cells become dehydrated and rigid
cation pump fails to function
Causes chronic non-spherocytic hemolytic anemia
=> excess haemolysis leads to jaundice and gall stones
What are the precursor stages of erythrocytes?
Hemocytoblasts -> proerythroblast -> early, late erythroblasts -> normoblast -> reticulocyte -> eyrthrocyte
How does acute hemolysis occur?
Acute hemolysis caused by exposure to oxidant stress
Causes Hb to precipitate into heinz bodies
What is menses?
Blood and other matter discharged rom the uterus during menstruation
Where are globin genes found?
The genes for globin chains occur in clusters on chromosomes
- 11 ( Ɣ β δ and 𝜺 )
- 16 (α and ζ)
Expression of β and α globin chains is closely regulated
What is the significance of Vit B12 and folate in erythropoiesis?
Both essential for RBC maturation and DNA synthesis
required for thymidine triphosphate formation
- (TTP nucleoside triphosphate used in vivo DNA
synthesis)
B12 is coenzyme for methionine synthase
- methylates homocysteine to methionine
What is AIHA anemia?
Autoimmune hemolytic anemia is a group of rare but serious blood disorders caused by antibody
production by the body against own red cells
Divided into cold/warm depending on the antibody’s strength of reaction with red cell at 37℃ or 40℃
