Anaemia and Polycythaemia

Question 1

Define anaemia.

Answer 1

Anaemia = reduction in amount of Hb in given blood volume below what would be expected in comparison with healthy subject of same age and gender.

RBC, Hct also reduced.

Question 2

In what two ways can anaemia occur?

Answer 2

Reduction in amount of Hb in blood stream.

Increase in volume of blood plasma.

Question 3

Why is reduction in absolute Hb considered the practical definition of anaemia?

Answer 3

Increased plasma volume in healthy people will be corrected as excess circulation fluid is excreted, so anaemia can be regarded as a decrease in absolute haemoglobin.

Question 4

Name some mechanisms through which anaemia can occur?

Answer 4

Reduced RBC production in bone marrow

Loss of blood from body

Reduced survival of circulating RBC

pooling of RBC in large spleen

Question 5

How is anaemia classified based on cell size?

Answer 5

microcytic (normally hypochromic)

normocytic (normally normochromic)

macrocytic (normally normochromic)

Question 6

Name some common causes of microcytic anaemia.

Answer 6

Defect in haem synthesis.

• iron deficiency
• anaemia of chronic disease.

Defect in globin synthesis (thalassaemia)

• defect in alpha chain syn (alpha thalassaemia)
• defect in beta chain syn (beta thalassaemia)

Question 7

How might macrocytic anaemia occur?

Answer 7

Macrocytic anaemia is usually due to abnormal haemopoiesis. RBC precursors continue to grow and synthesise haemoglobin but fail to divide normally.

: . RBC are larger than normal.

Question 8

What is a megaloblast?

Answer 8

An abnormal bone marrow erythroblast. Larger than normal with nucleo-cytoplasmic disassocation.

Question 9

Name some causes of macrocytic anaemia.

Answer 9

Megaloblastic erythropoiesis (nucleus maturation delay while cytoplasm grows) - e.g. due to Vit B12/folic acid deficiency.

Pre-mature release of cells from bone marrow (young RBC 20% larger).

Liver disease/ethanol toxicity.

Use of drugs interfering with DNA synthesis.

Significant blood lost (with sufficient iron stores)

Haemolytic anaemia.

Question 10

How can haemolytic anaemia be classified?

Answer 10

Intrinsic/extrinsic causes of RBC abnormality.

Whether it is inherited or acquired.

Whether it is intravascular or extravascular.

Question 11

Diagram comparing inherited and acquired haemolytic anaemia

Answer 11

Question 12

Name the mechanisms of normocytic anaemia.

Answer 12

Recent blood loss

Failure of RBC production

Pooling of RBC in spleen

Question 13

Name some causes of normocytic anaemia.

Answer 13

Peptic ulcer

Oesophageal varices

Trauma

Failure of RBC production

• iron deficiency, early stages.
• renal failure
• bone marrow failure/suppression
• bone marrow infiltration.

Hypersplenism

Question 14

When should you suspect haemolytic anaemia?

Answer 14

Otherwise inexplicable.

Evidence of abnormal RBC

Evidence of increased RBC breakdown

Evidence of increased bone marrow activity.

Question 15

In hereditary spherocytosis haemolytic anaemia what is the site of defect?

Answer 15

membrane

Question 16

What is the site of defect associated with sickle cell anaemia (haemolytic anaemia)

Answer 16

Hb

Question 17

What defective pathway is associated with pyruvate kinase deficiency (haemolytic anaemia)?

Answer 17

glycolytic pathway

Question 18

What defect is associated with glucose-6-phosphate dehydrogenase deficiency (haemolytic anaemia)?

Answer 18

Pentose shunt.

Question 19

Table to show site of defects and examples in acquired haemolytic anaemia

Answer 19

Question 20

What is hereditary spherocytosis?

Answer 20

haemoltyic anaemia or chronic compensated haemolysis resulting from inherited intrinsic defect of RBC membrane

Cell loses membrane in splene –> spherocytic.

Question 21

Explain the consequences of hereditary spherocytosis.

Answer 21

RBC less flexible - removed prematurely by psleen (extravascular haemolysis).

Bone marrow increased RBC output –> polychromasia and reticulocytosis.

Haemolysis –> jaundice + gallstones.

Question 22

Name an osmotic characteristic of spherocytes.

Answer 22

Prone to haemolyse when osmotic pressure is reduced.

Question 23

How can hereditary spherocytosis be treated?

Answer 23

Splenectomy.

Good diet.

Folic acid tablets.

Question 24

What is the role of G6PD?

Answer 24

important enzyme in pentose phosphate shunt.

Essential for protection of RBC from oxidant damage.

Question 25

What can cause G6PD deficiency?

Answer 25

Extrinsic oxidants - foodstuffs, chemicals, drugs.

Genetic - on X chromosome no normally hemizygous males.

Question 26

What are the effects of G6PD deficiency?

Answer 26

Intermittent, severe intravascular haemolysis due to infection/exposre to oxidant.

Hb denatured - round inclusions called Heinz bodies form.

Question 27

How is G6PD deficiency treated?

Answer 27

Blood transfusion for acute haemolysis.

Prevention of exposure to oxidants.

Question 28

Explain how autoimmune haemolytis anaemia arises.

Answer 28

Production of autoantibodis directed at red cell mutagens.

Immunoglobin on RBC membrane recognised by splenic macrophages –> spherocytosis.

Complement components can bind to immunoglobulin molecule and can be recognised by splenic macrophages

Question 29

What causes removal of RBC from circulation in the spleen in autoimmune haemlytic anaemia.

Answer 29

Spherocytes are less flexible than normal RBC

combination of cell rigidity and recognition of antibody and complement in RBC surface by splenic macrophages –> removal of cells from circulation by spleen.

Question 30

How is autoimmune haemolytic anaemia diagnosed?

Answer 30

• Finding spherocytes and an increased reticulocyte count
• Detecting immunoglobulin ± complement on the red cell surface
• Detecting antibodies to red cell antigens or other autoantibodies in the plasma

Question 31

How is autoimmune haemoylytic anaemia treated?

Answer 31

Corticosteroids and other immunosuppressive agents.

Splenectomy

Question 32

How is microangiopathic haemolytic anaemia treated?

Answer 32

Removing cause - e.g. treating hypertension or stopped causative drug.

Plasma exchange when caused by antibody in plasma that is leading to fibrin deposition.