CVS Red blood cell production and survival

Question 1

What is the first recognisable RBC precursor in marrow?

Answer 1

proerythroblast is first recognisable RBC
precursor in marrow

Question 2

Where does RBC mature to late normoblast?

Answer 2

maturation to late normoblast in marrow

Question 3

How is RBC related to ambient O2 pressure?

Answer 3

Number of rbc is inversely related to ambient O2 pressure

Question 4

What is the key regulator of feedback loop in RBC production?

Answer 4

Key regulator of feedback loop is EPO

Question 5

What are the steps involved in regulation of RBC production?

Answer 5

1. The stimulus would be hypoxia due to decreased RBC count, decreased amount of haemoglobin, or decreased availability of O2
2. This reduces O2 levels in blood
3. This causes kidney and liver, to a smaller extent, to release erythropoietin
4. Erythropoietin stimulates red bone marrow
5. Enhanced erythropoiesis increases RBC count
6. This increases O2, carrying ability of blood

Question 6

What does HIF enhance expression of?

Answer 6

HIF enhances expression of
iron-absorbing gene.

Question 7

What does HIF enhance expression of?

Answer 7

HIF enhances expression of
iron-absorbing gene.

Question 8

What does iron serve as in RBC production and what is it regulated by?

Answer 8

Iron serves as an important
substrate; and is regulated
by hepcidin.

Question 9

Where is 5-10% of protein absorbed in the body?

Answer 9

5-10% absorbed (1mg) principally in duodenum and jejunum.

Question 10

What regulates the absorption of RBC production?

Answer 10

DMT-1 and ferroportin regulate

Question 11

What regulates the absorption of RBC production?

Answer 11

DMT-1 and ferroportin regulate

Question 12

What are the causes of iron deficiency?

Answer 12

-Poor diet
-Increased demand
-Chronic blood loss
-Malabsorption

Question 12

What are the causes of iron deficiency?

Answer 12

-Poor diet
-Increased demand
-Chronic blood loss
-Malabsorption

Question 12

What are the causes of iron deficiency?

Answer 12

-Poor diet
-Increased demand
-Chronic blood loss
-Malabsorption

Question 12

What are the causes of iron deficiency?

Answer 12

-Poor diet
-Increased demand
-Chronic blood loss
-Malabsorption

Question 12

What are the causes of iron deficiency?

Answer 12

-Poor diet
-Increased demand
-Chronic blood loss
-Malabsorption

Question 13

What do labs show in iron deficiency?

Answer 13

Low Hb level; Microcytic, hypochromic anaemia, [MCV < 80fl(m)

Question 14

What are the normal MCV levels?

Answer 14

MCV: Normal: male 80-95; female 78-95

Question 15

What are 2 things essential for RBC maturation and DNA synthesis?

Answer 15

Both essential for RBC maturation & DNA synthesis

Question 16

Why are both vitamin B12 and folic acid needed in in RBC maturation and DNA synthesis?

Answer 16

Both needed for formation of thymidine triphosphate.

Question 17

What is vitamin B12 involved with in RBC maturation and DNA synthesis?

Answer 17

B12 is coenzyme for methionine synthase in methylation of homocysteine to
methionine.

Question 18

What does deficiency of vitamin B12 and folic acid lead to?

Answer 18

Deficiency leads to failure of nuclear maturation.

Question 19

What are causes of vitamin B12 deficiency?

Answer 19

-Inadequate intake
-Absorption defect
-IF deficiency

Question 20

What are causes of vitamin folate deficiency?

Answer 20

-Inadequate intake
-Absorption defect
-Increased demand/loss
-Drugs

Question 21

What are the labs like for folate and B12 deficiencies?

Answer 21

MCV > 95fl; oval macrocytes;
Megaloblastic anaemia, with macroovalocytes and hypersegmented neutrophil.

Question 22

What is treatment for B12 deficiency?

Answer 22

B12 - Hydroxycobalamin: 1mg im

Question 23

What is treatment for folate deficiency?

Answer 23

Folate: -Folic acid: 5mg/day oral

Question 24

How can renal disease affect RBC production?

Answer 24

ineffective erythropoiesis

Question 25

How can reduced bone marrow erythroid cells affect RBC production?

Answer 25

 Aplastic anaemia
 Marrow infiltration by leukaemia or other malignancies

Question 26

What are the acquired classification of haemolytic anaemia?

Answer 26

Immune:
-Autoimmune
-Alloimmune
Non-immune:
-Red cell fragmentation
-Infection:secondary

Question 27

What are the hereditary classification of haemolytic anaemia?

Answer 27

Red cell membrane disorders:
-Hereditary spherocytosis
-Hereditary elliptocytosis
Red cell metabolism
-G6PD deficiency
-PK deficiency
Haemoglocinopathies
-Sickle cell diseases
-Thalassaemias

Question 28

What are the metabolic processes included in RBC survival?

Answer 28

Glycolytic Pathway (Embden-Meyerhof pathway )
Hexose Monophosphate Shunt (or PPP)

Question 29

What does the glycolytic pathway generate and what is it for?

Answer 29

Generates energy in ATP;
to maintain red cell shape and
deformability
To regulate intracellular cation
conc. via cation pumps (Na/K
pump),

Question 30

What happens in PK deficiency and what happens?

Answer 30

ATP is depleted:
cells lose large amount of potassium & water, becoming dehydrated & rigid.

Question 31

What can PK deficiency cause?

Answer 31

causes chronic non-spherocytic haemolytic anaemia

Question 32

What happens in G6PD deficiency and what can this cause?

Answer 32

 NADPH and GSH generation impaired
-Acute haemolysis on exposure to oxidant stress: oxidative drugs,
fava (broad) beans or infections
-Hb precipitation – Heinz bodies

Question 33

What happens to shape of RBC in hereditary spherocytosis?

Answer 33

Loss of membrane integrity, the RBCs become spherical

Question 34

What causes the common hereditary haemoltic anaemia in northen europe?

Answer 34

deficiency in proteins with vertical interactions between the membrane
skeleton and the lipid bilayer: e.g. ankyrin def

Question 35

What causes hereditary elliptocytosis?

Answer 35

mutations in horizontal interactions e.g. spectrin, ankyrin; actin, protein
4.1 deficiency.

Question 36

What are the genes for globin chain disorders and what chromosomes does it occur on?

Answer 36

11 (ε, γ, δ and β)
16 (ζ and α)

Question 37

What can mutations or deletion of alpha and beta globin chains lead to?

Answer 37

a) Abnormal synthesis of globin chain as in Sickle Cell Diseases.
b) Reduced rate of synthesis of normal globin chains as in Thalassaemia.

Question 38

What are clinically significant sickling syndromes?

Answer 38

 HbSS
 HbSC
 HbS-D Punjab
 HbS- O Arab
 HbS- β thalassaemia

Question 39

What point mutation occurs which leads to sickle cell disease and how?

Answer 39

1. Point mutation in the β globin gene:
   e.g. glutamic acid → valine (HbS)
2. Insoluble Hb tetramer when
   deoxygenated → polymerisation
3. ‘Sickle’ shaped cells

Question 40

What is there a loss of in beta thalassaemia?

Answer 40

 Loss of 1 -chain causes mild microcytic anaemia (thalassaemia trait)
 Loss of both (0) causes thalassaemia major

Question 41

What happens in beta thalassaemia?

Answer 41

Excess α-chains precipitate in erythroblasts causing haemolysis and
ineffective erythropoiesis.

Question 42

What can there be a loss of in alpha-thalassaemia?

Answer 42

There can be loss of 1, 2, 3 or 4 alpha chains.

Question 43

What is transfusion dependant on in beta thalassaemia major?

Answer 43

dependant on 1sy ur of lige

Question 44

What happens if not transfused in 1st year of life?

Answer 44

Failure to thrive
Progressive hepatosplenomegaly
Bone marrow expansion – skeletal
abnormalities
Death in 1st 5 years of life from anaemia

Question 45

What are the side effects of transfusion in beta thalassaemia major?

Answer 45

Iron overload
- Endocrinopathies
- Heart failure
- Liver cirrhosis