Lecture 8 – RBC production and survival

Question 1

RBC production - ON DIAGRAM

Answer 1

ON DIAGRAM

Question 2

Hormonal Control of Erythropoiesis (5)

Answer 2

Hypoxia caused by decresed RBC/O2/Hb.
Increases of EPO in kidney.
EPO to red bone marrow.
Increases RBC.
Increases O2 carried in blood.

Question 3

What is required for erythropoiesis? (4)

Answer 3

Vitamin B12/Folic acid.
Fe2+.
Amino acids.
EPO.

Question 4

Iron (5)

Answer 4

• Sources  Meat, eggs, vegetables, dairy foods.
• Absorption
• Normal Western diet provides 15mg daily.
• 5-10% absorbed (1mg) principally in duodenum and jejunum.
• Gastric secretion (HCl) and ascorbic acid help absorption.

Question 5

Vitamin B12 and Folic Acid (4)

Answer 5

• Both essential for RBC maturation DNA synthesis.
o Both needed for formation of THYMIDINE TRIPHOSPHATE.
o B12 is coenzyme for methionine synthase in methylation of homocysteine to methionine.
• Deficiency in either of them causes abnormal, diminished DNA, leading to failure of nuclear maturation.

Question 6

What happens in folate and B12 deficiencies? (4)

Answer 6

• Megaloblastic anemia, with macroovalocytes and hypersegmented neutrophil.
Megaloblastic anemia - A condition in which the bone marrow produces unusually large, structurally abnormal, immature red blood cells (megaloblasts).
• Treatment
 B12 - Hydroxycobalamin: 1mg im
 Folate: -Folic acid: 5mg/day oral

Question 7

Causes of Vitamin B12 deficiency (10)

Answer 7

ON DIAGRAM

Question 8

Causes of Folate deficiency (12)

Answer 8

ON DIAGRAM

Question 9

Other causes of failure of RBC production (4)

Answer 9

• Renal dx - ineffective erythropoiesis.
• Reduced BM erythroid cells.
o Aplastic anaemia.
o Marrow infiltration by leukaemia or other malignancies.

Question 10

RBC Survival and Destruction (1)
Stress placed on RBC (4)
Longevity and survival (3)

Answer 10

•	Energy supply in cells but RBC unable to carry out oxidative phosphorylation and protein synthesis.
•	Stress placed on RBC
•	Life span 120 days.
•	300 miles travelled through microcirculation.
•	8μm diameter.
•	Capillaries as small as 3μm.
•	Longevity and survival depends on 
o	Membrane integrity.
o	Hb structure.
o	Presence of red cell enzymes.

Question 11

Classification of Haemolytic Anaemia (6) - ON DIAGRAM

Answer 11

ON DIAGRAM

Question 12

Classification of Haemolytic Anaemia - Acquired

Answer 12

ON DIAGRAM

Question 13

Classification of Haemolytic Anaemia - Hereditary

Answer 13

ON DIAGRAM

Question 14

Classification of Haemolytic Anaemia - Intra/Extravascular Haemolysis

Answer 14

ON DIAGRAM

Question 15

Globin disorders (5)

Answer 15

• Globin genes cluster on chromosomes.
• Expression of alpha and beta globin closely balanced.
• Mutations or deletions may lead to;
o Abnormal synthesis of globin chain as in Sickle Cell Diseases.
o Reduced rate of synthesis of normal α- or -globin chains as in Thalassaemias.

Question 16

Sickle cell disease (3)

Answer 16

ON DIAGRAM

Question 17

Thalassemia (5)

Answer 17

• Beta-thalassaemia
• Loss of 1 -chain causes mild microcytic anaemia (thalassaemia trait)
• Loss of both (0) causes thalassaemia major
• Excess α-chains precipitate in erythroblasts causing haemolysis and ineffective erythropoiesis.
• Alpha-thalassaemia
• There can be loss of 1, 2, 3 or 4 alpha chains.

Question 18

Red Cell Enzymes (4)

Answer 18

• Two main enzymes
o Glucose-6-Phosphate Dehydrogenase (G-6-PD)
o Pyruvate Kinase (PK)

•	Support 2 main Metabolic Pathways
o	Pentose Phosphate pathway
Using G6PD
o	Glycolytic pathway 
Using PK

Question 19

What happens in G6PD deficiency? (4)

Answer 19

• NADPH and GSH generation impaired.
• Acute haemolysis on exposure to oxidant stress: oxidative drugs, fava beans (broad beans) or infections.
• Hb precipitation – Heinz bodies.
• G6PD deficiency most common known enzymopathy, estimated to affect 400 million people worldwide but evolutionary beneficial.

Question 20

What happens in PK (Pyruvate Kinase) deficiency? (4)

Answer 20

 What happens in PK deficiency?
 ATP-depleted cells lose large amount of potassium & water, becoming dehydrated & rigid.
 Because cation pumps fail to function.
 Causes chronic non-spherocytic haemolytic anaemia.
 Excess haemolysis leads to jaundice, gallstones.