Red blood cell production and survival

Question 1

what stimulates erythropoiesis?

Answer 1

• Stimulus
○ Hypoxia due to decreased RBC count, decreased amount of Hb
Reduced O2 levels in blood

Question 2

Steps of erythropoiesis

Answer 2

• Kidney and liver release erythropoietin
• Erythropoietin stimulates red bone marrow
• Enhanced erythropoiesis increase RBC count
Increases O2 carrying ability of blood

Question 3

What are the requirements of erythropoiesis?

Answer 3

• Vitamin B 12 and folic acid
• Amino acids and Fe2+
• Epo
• Gives 10^12 RBC/day

Question 4

What are the sources of Iron

Answer 4

Meat, eggs, vegetables, dairy

Question 5

Absorption of Iron and what helps with absorption

Answer 5

• Absorption:
○ Normal western diet provides 15mg daily
§ 5-10% absorbed principally in duodenum and jejunum
HCl and ascorbic acid help absorption

Question 6

How is haem synthesised?

Answer 6

• Succinyl CoA and glycine combine in the presence of vitamin B6 and δ-ALA synthase to form δ-ALA

δ-ALA converted into protoporphyrin which combines with Iron to form Haem

Question 7

How is haemoglobin synthesised?

Answer 7

• Transferrin brings in the Fe2+ to the cells mitochondria where it combines with protoporphyrin forming haem

The haem leaves the mitochondria and combines with alpha and beta 2 globin to form haemoglobin

Question 8

What are the causes of iron deficiency?

Answer 8

• Causes:
	○ Decreased uptake:
		§ Inadequate intake
		§ Malabsorption
	○ Increased demand:
		§ Pregnancy
		§ Growth spurt
	○ Increased loss
		§ GI bleed
                § Excess loss in menses

Question 9

Why is vitamin B12 and folic acid essential and why?

Answer 9

• Essential for RBC maturation
○ Needed for formation of thymidine triphosphate

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

Question 10

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

Answer 10

• Deficiency of these causes abnormal DNA
○ Leads to failure of nuclear maturation

Megaloblastic anemia occurs

Question 11

What is the treatment for deficiency of vitamin B12 and folic acid?

Answer 11

§ B12-Hydroxycobalamin 1mg

Folate-Folic acid: 5 mg/day oral

Question 12

Causes of Vitamin B12 deficiency

Answer 12

○ Inadequate intake
	§ Vegans
○ Absorption defect:
	§ Tropical sprue
	§ Coeliac dx
	§ Blind loop syndromes
○ IF deficiency:
	§ Pernicious anaemia
	§ Crohn's
        § Gastrectomy and others

Question 13

Causes of Folate deficiency

Answer 13

○ Inadequate intake:
	§ Poor nutrition
○ Absorption defect:
	§ Coeliac disease
	§ Crohn's dx
	§ Tropical sprue
○ Increase in demand:
	§ Pregnancy 
	§ Haemolysis
	§ Cancer
○ Drugs:
           Anticonvulsants

Question 14

What are the causes of faliure of RBC production?

Answer 14

• Renal dx-ineffective erythropoiesis
• Reduced Bone Marrow erythroid cells:
○ Aplastic anaemia
Marrow infiltration by leukaemia or other malignancies

Question 15

What is the stress placed on RBC?

Answer 15

• Life span of 120 days
• 300 miles travelled through microcirculation
• 8um diameter
• Capillaries as small as 3um

Question 16

What does longevity and survival of RBC depend on?

Answer 16

• Membrane integrity
• Hb structure
Presence of red cell enzymes

Question 17

What causes hereditary haemolytic anaemia?

Answer 17

• Haemoglobinopathies:
	○ Sickle cell diseases
	○ Thalassaemia's
• Red cell enzymopathies
	○ G6PD deficiency
	○ PK deficiency
• Red cell membrane disorders
	○ Hereditary spherocytosis
           Hereditary elliptocytosis

Question 18

What can cause acquired haemolytic anaemia?

Answer 18

• Immune:
	○ Autoimmune
	○ Alloimmune
	○ Drug induced
• Non-immune:
	○ Red cell fragmentation
	○ Infection
           Secondary

Question 19

What can a mutation or deletion of base in globin gene cause?

Answer 19

• Mutations or deletion may lead to:
○ Abnormal synthesis of globin chain as in sickle cell diseases
Reduced rate of synthesis of normal alpha or beta globin chains as in thalassaemia’s

Question 20

What is sickle cell disease?

Answer 20

Group of Hb disorders with inherited sickle beta-globin gene

Question 21

What is the most common sickle cell disease?

Answer 21

Sickle cell anaemia-homozygous(HbSS)most common of all SCD

Question 22

What mutation occurs on beta globin gene which causes HbSS?

Answer 22

Substitution of adenine with thymine giving rise to val instead of glu.

Question 23

What are heterozygote conditions in sickle cell disease?

Answer 23

○ Heterozygote conditions:
	§ HbS
	§ HbSC
	§ HbSD
          HbSE

Question 24

What is beta thalassaemia caused by and what does it result in?

Answer 24

○ Loss of 1 beta chain

resulting in mild microcytic anaemia

Question 25

What is thalassaemia major caused by?

Answer 25

Loss of both beta chains causes thalassaemia major

Question 26

What occurs in beta thalassaemia?

Answer 26

Excess alpha chains precipitate in erythroblasts causing haemolysis and ineffective erythropoiesis

Question 27

What is alpha thalassaemia caused by?

Answer 27

• Alpha thalassaemia:

Loss of 1-4 alpha chains

Question 28

What are the two main enzymes in RBC

Answer 28

○ G6PD

Pyruvate kinase

Question 29

What 2 main metabolic pathways are supported by main RBC enzymes

Answer 29

○ Pentose phosphate pathway

Glycolytic pathway

Question 30

What happens in G6PD deficiency?

Answer 30

• NADPH and GSH generation impaired
○ Acute haemolysis on exposure to oxidant stress
Hb precipitaion-Heinz bodies

Question 31

What is G6PD known as?

Answer 31

Most common known enzymopathy, estimated to affect 400 million people worldwide

Question 32

What happens in PK deficiency and what is it due to?

Answer 32

• ATP-depleted cells lose large amount of potassium and water, becoming dehydrated and rigid

Due to Cation pumps failing to function

Question 33

What does PK deficiency cause?

Answer 33

Causes chronic non-spherocytic haemolytic anaemia

Question 34

What does excess haemolysis lead to?

Answer 34

Excess haemolysis leads to jaundice, gallstone