CVS Red blood cell production and survival Flashcards
What is the first recognisable RBC precursor in marrow?
proerythroblast is first recognisable RBC
precursor in marrow
Where does RBC mature to late normoblast?
maturation to late normoblast in marrow
How is RBC related to ambient O2 pressure?
Number of rbc is inversely related to ambient O2 pressure
What is the key regulator of feedback loop in RBC production?
Key regulator of feedback loop is EPO
What are the steps involved in regulation of RBC production?
- The stimulus would be hypoxia due to decreased RBC count, decreased amount of haemoglobin, or decreased availability of O2
- This reduces O2 levels in blood
- This causes kidney and liver, to a smaller extent, to release erythropoietin
- Erythropoietin stimulates red bone marrow
- Enhanced erythropoiesis increases RBC count
- This increases O2, carrying ability of blood
What does HIF enhance expression of?
HIF enhances expression of
iron-absorbing gene.
What does HIF enhance expression of?
HIF enhances expression of
iron-absorbing gene.
What does iron serve as in RBC production and what is it regulated by?
Iron serves as an important
substrate; and is regulated
by hepcidin.
Where is 5-10% of protein absorbed in the body?
5-10% absorbed (1mg) principally in duodenum and jejunum.
What regulates the absorption of RBC production?
DMT-1 and ferroportin regulate
What regulates the absorption of RBC production?
DMT-1 and ferroportin regulate
What are the causes of iron deficiency?
-Poor diet
-Increased demand
-Chronic blood loss
-Malabsorption
What are the causes of iron deficiency?
-Poor diet
-Increased demand
-Chronic blood loss
-Malabsorption
What are the causes of iron deficiency?
-Poor diet
-Increased demand
-Chronic blood loss
-Malabsorption
What are the causes of iron deficiency?
-Poor diet
-Increased demand
-Chronic blood loss
-Malabsorption
What are the causes of iron deficiency?
-Poor diet
-Increased demand
-Chronic blood loss
-Malabsorption
What do labs show in iron deficiency?
Low Hb level; Microcytic, hypochromic anaemia, [MCV < 80fl(m)
What are the normal MCV levels?
MCV: Normal: male 80-95; female 78-95
What are 2 things essential for RBC maturation and DNA synthesis?
Both essential for RBC maturation & DNA synthesis
Why are both vitamin B12 and folic acid needed in in RBC maturation and DNA synthesis?
Both needed for formation of thymidine triphosphate.
What is vitamin B12 involved with in RBC maturation and DNA synthesis?
B12 is coenzyme for methionine synthase in methylation of homocysteine to
methionine.
What does deficiency of vitamin B12 and folic acid lead to?
Deficiency leads to failure of nuclear maturation.
What are causes of vitamin B12 deficiency?
-Inadequate intake
-Absorption defect
-IF deficiency
What are causes of vitamin folate deficiency?
-Inadequate intake
-Absorption defect
-Increased demand/loss
-Drugs
What are the labs like for folate and B12 deficiencies?
MCV > 95fl; oval macrocytes;
Megaloblastic anaemia, with macroovalocytes and hypersegmented neutrophil.
What is treatment for B12 deficiency?
B12 - Hydroxycobalamin: 1mg im
What is treatment for folate deficiency?
Folate: -Folic acid: 5mg/day oral
How can renal disease affect RBC production?
ineffective erythropoiesis
How can reduced bone marrow erythroid cells affect RBC production?
Aplastic anaemia
Marrow infiltration by leukaemia or other malignancies
What are the acquired classification of haemolytic anaemia?
Immune:
-Autoimmune
-Alloimmune
Non-immune:
-Red cell fragmentation
-Infection:secondary
What are the hereditary classification of haemolytic anaemia?
Red cell membrane disorders:
-Hereditary spherocytosis
-Hereditary elliptocytosis
Red cell metabolism
-G6PD deficiency
-PK deficiency
Haemoglocinopathies
-Sickle cell diseases
-Thalassaemias
What are the metabolic processes included in RBC survival?
Glycolytic Pathway (Embden-Meyerhof pathway )
Hexose Monophosphate Shunt (or PPP)
What does the glycolytic pathway generate and what is it for?
Generates energy in ATP;
to maintain red cell shape and
deformability
To regulate intracellular cation
conc. via cation pumps (Na/K
pump),
What happens in PK deficiency and what happens?
ATP is depleted:
cells lose large amount of potassium & water, becoming dehydrated & rigid.
What can PK deficiency cause?
causes chronic non-spherocytic haemolytic anaemia
What happens in G6PD deficiency and what can this cause?
NADPH and GSH generation impaired
-Acute haemolysis on exposure to oxidant stress: oxidative drugs,
fava (broad) beans or infections
-Hb precipitation – Heinz bodies
What happens to shape of RBC in hereditary spherocytosis?
Loss of membrane integrity, the RBCs become spherical
What causes the common hereditary haemoltic anaemia in northen europe?
deficiency in proteins with vertical interactions between the membrane
skeleton and the lipid bilayer: e.g. ankyrin def
What causes hereditary elliptocytosis?
mutations in horizontal interactions e.g. spectrin, ankyrin; actin, protein
4.1 deficiency.
What are the genes for globin chain disorders and what chromosomes does it occur on?
11 (ε, γ, δ and β)
16 (ζ and α)
What can mutations or deletion of alpha and beta globin chains lead to?
a) Abnormal synthesis of globin chain as in Sickle Cell Diseases.
b) Reduced rate of synthesis of normal globin chains as in Thalassaemia.
What are clinically significant sickling syndromes?
HbSS
HbSC
HbS-D Punjab
HbS- O Arab
HbS- β thalassaemia
What point mutation occurs which leads to sickle cell disease and how?
- Point mutation in the β globin gene:
e.g. glutamic acid → valine (HbS) - Insoluble Hb tetramer when
deoxygenated → polymerisation - ‘Sickle’ shaped cells
What is there a loss of in beta thalassaemia?
Loss of 1 -chain causes mild microcytic anaemia (thalassaemia trait)
Loss of both (0) causes thalassaemia major
What happens in beta thalassaemia?
Excess α-chains precipitate in erythroblasts causing haemolysis and
ineffective erythropoiesis.
What can there be a loss of in alpha-thalassaemia?
There can be loss of 1, 2, 3 or 4 alpha chains.
What is transfusion dependant on in beta thalassaemia major?
dependant on 1sy ur of lige
What happens if not transfused in 1st year of life?
Failure to thrive
Progressive hepatosplenomegaly
Bone marrow expansion – skeletal
abnormalities
Death in 1st 5 years of life from anaemia
What are the side effects of transfusion in beta thalassaemia major?
Iron overload
- Endocrinopathies
- Heart failure
- Liver cirrhosis
