Anaemia

Question 1

What is anaemia

Answer 1

Reduction in the amount of haemoglobin in a given volume of blood below what would be expected in comparison with a healthy subject of the same age and gender

Question 2

What in a FBC is reduced in anaemia

Answer 2

Hb

Usually RBC and Hct

Question 3

Describe the general pathogenesis of anaemia

Answer 3

Reduction in the absolute amount of haemoglobin in the blood stream
Occasionally due to an increase in volume plasma (cannot persist as excess fluid is excreted)

Question 4

Give an latrogenic cause of anaemia

Answer 4

giving too much IV fluid too fast

Question 5

What are the mechanisms of anaemia

Answer 5

Reduced production of red cells/haemoglobin in the bone marrow
Loss of blood from the body
Reduced survival of red cells in the circulation
Pooling of red cells in a very large spleen

Question 6

What are the causes of microcytic anaemia

Answer 6

Defect in haem synthesis

• iron deficiency
• anaemia of chronic disease

Defect in global synthesis (thalassaemia)

• Defect in α chain synthesis
• Defect in β chain synthesis

Question 7

What is macrocytic anaemia

Answer 7

Average cell size is increased

Question 8

Describe the general pathogenesis of macrocytic anaemia

Answer 8

Usually abnormal haemopoiesis

The red cell precursors continue to synthesise haemoglobin and other cellular proteins but fail to divide normally

Question 9

What are the two types of causes of macrocytic anaemia

Answer 9

Premature release of RBCs from bone marrow

Megaloblastic erythropoiesis

Question 10

Describe the premature release of RBCs in macrocytic anaemia and what might cause it

Answer 10

Reticulocytes are 20% larger than mature RBCs

Excess haemolysis
Recent major haemorrhage (if the body has plentiful iron stores)

Question 11

What is a megaloblast

Answer 11

Abnormal bone marrow erythroblast (RBC precursors)

Larger than normal

Question 12

What occurs in megaloblastic erythropoiesis

Answer 12

Maturation of the nucleus is delayed but the cell keeps on growing and synthesising protein in the meantime (nuclei-cytoplasmic dissociation)

Question 13

What are the common causes of megaloblastic anaemia

Answer 13

Vitamin B12 or folic acid deficiency
Drugs interfering with DNA synthesis
Liver disease
Ethanol/alcohol toxicity

Question 14

What are the mechanisms of normocytic anaemia

Answer 14

Recent blood loss
Failure of production of red cells
Pooling of red cells in the spleen

Question 15

What can cause haemorrhage that causes normocytic anaemia

Answer 15

• trauma
• peptic ulcer
• oesophageal varices

Question 16

What can cause failure of RBC production (normocytic anaemia)

Answer 16

Renal failure - lack of erythropoietin
Early stage iron deficiency or anaemia of chronic disease (ACD)
Bone marrow suppression

Question 17

What can cause pooling of RBCs in the spleen

Answer 17

portal hypertension

Hypersplenism e.g. portal cirrhosis

Question 18

What is haemolytic anaemia and what can it be due to

Answer 18

Anaemia resulting from shortened survival of red cells in the circulation

May be due to intrinsic abnormality of the red cells or extrinsic factors acting on normal red cells

Question 19

What is the difference between inherited and acquired haemolytic anaemia

Answer 19

Inherited - can result from abnormalities in the cell membrane, haemoglobin or enzymes in the red cell

Acquired - usually results from extrinsic factors such as micro-organisms, chemicals or drugs that damage the red cell

Question 20

What is the difference between intravascular and extravascular haemolysis

Answer 20

Haemolysis is partly intravascular and partly extravascular

Intravascular - if there is very acute damage to the red cell

Extravascular - Defective red cells are removed by the spleen

Question 21

Give examples of causes of inherited haemolytic anaemia

Answer 21

Defective:
Cell membrane - Hereditary spherocytosis

Haemoglobin - Sickle cell

Glycolysis - pyruvate kinase deficiency

Enzymes of pentose shunt - G6PD deficiency

Question 22

Give examples of causes of acquired haemolytic anaemia

Answer 22

Damage to:
Cell membrane - Autoimmune haemolytic anaemia or snake bite
Whole cell - Microangiopathic haemolytic anaemia, malaria

Damage caused by:
Oxidant exposure - dapsone or primaquine
microorganisms - malaria

Question 23

What is the role of glucose-6-phosphate dehydrogenase

Answer 23

G-6-P dehydrogenase is an important enzyme in the pentose phosphate shunt
It is crucial for protecting the RBC from oxidative damage

Question 24

What can cause oxidant damage

Answer 24

Broad beans, naphthalene (in moth balls)

Dapsone or primaquine (drugs).

Question 25

What does a deficiency in glucose-6-phosphate dehydrogenase lead to

Answer 25

Increases vulnerability to oxidants | It causes intermittent, severe intravascular haemolysis due to infection or oxidant exposure.

Question 26

What kind of cells may be found in the blood in glucose-6-phosphate dehydrogenase deficiency

Answer 26

Irregularly contracted cells Hb is denatured and forms around inclusions called Heinz bodies which can be detected The spleen removes Heinz bodies, leaving defective RBCs.

Question 27

Which sex does glucose-6-phosphate dehydrogenase deficiency affect more and why

Answer 27

The G6PD gene is on the X chromosome, so men are more frequently affected than women.

Question 28

What does autoimmune haemolytic anaemia result from

Answer 28

Autoantibodies specific to RBC antigens

Question 29

Explain how the presence autoantibodies for RBC antigens lead to anaemia

Answer 29

Splenic macrophages recognise the antigen-antibody complex and remove it along with part of the cell membrane, leading to spherocytosis. The spherocytes then get removed by the spleen, causing the anaemia.

Question 30

How is autoimmune haemolytic anaemia diagnosed

Answer 30

Spherocytes found Increased reticulocyte count Immunoglobulin and complement on red cell surface detected Antibodies to red cell antigens or other autoantibodies in the plasma detected

Question 31

How is autoimmune haemolytic anaemia treated

Answer 31

Immunosuppression (e.g. with steroids) | Splenectomy for severe cases

Question 32

Describe hereditary spherocytosis

Answer 32

Haemolytic anaemia or chronic compensated haemolysis resulting from an inherited intrinsic defect of the red cell membrane After entering the circulation the cells lose membrane in the spleen and thus become spherocytic

Question 33

How does hereditary spherocytosis lead to jaundice

Answer 33

Spherocytes are less flexible and are removed prematurely by the spleen (extravascular haemolysis) The bone marrow responds nay increasing output of red cells, leading to polychromasia and reticulocytosis Leads to increased bilirubin production, jaundice and gall stones

Question 34

What is the osmotic fragility test

Answer 34

Spherocytes are more prone to haemolyse when osmotic pressure is reduced

Question 35

How is hereditary spherocytosis treated

Answer 35

Splenectomy Good diet so secondary folic acid deficiency does not occur One folic acid tablet taken daily