Anaemia

Question 1

WHAT IS ANAEMIA?

Answer 1

A 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 is shown in the blood count of an anaemic (Hb, RBC, Hct)

Answer 2

• Hb is reduced

- RBC and Hct are also reduced

Question 3

What is pseudo anaemia

Answer 3

• Anaemia from an increase in volume of plasma rather than due to a decrease in Hb

Question 4

4 mechanisms of anaemia?

Answer 4

1. Reduced production of red cells/Hb in bone marrow
2. Loss of blood from the body
3. Reduced survival of red cells in the circulation
4. Pooling of red cells in a very large spleen

Question 5

Classification of anaemia and what kinda chromic is it

Answer 5

MICROCYTIC (usually also hypochromic)
NORMOCYTIC (usually normochromic)
MACROCYTIC (usually normochromic)

Question 6

Common causes of microcytic anaemia? )2)

Answer 6

• Defect in haem synthesis

- Defect in globin synthesis (thalassaemia)

Question 7

Common cause of macrocytic anaemia?

Answer 7

• Usually result from abnormal haemopoiesis so that the red cell precursors continue to synthesise Hb and other cellular proteins but they fail to divide like normal
• As a result, red cells end up larger than normal

Question 8

What defects in haem synthesis can you get (2)

Answer 8

Iron deficiency – can be due to dietary problems or blood loss
Anaemia of chronic disease – anaemia in people with chronic inflammation, e.g. chronic rheumatoid arthritis leads to a reduced rate of synthesis of haemoglobin. Initially is normocytic normochromic but chronically becomes hypochromic and microcytic

Question 9

What disease causes defects in globing synthesis

Answer 9

thalassaemia

Question 10

What is megaloblastic anaemia

Answer 10

a problem in DNA synthesis causing a delay in maturation of the nucleus while the cytoplasm continues to mature and so the cell continues to grow

Question 11

• A megaloblast is an abnormal….

Answer 11

bone marrow erythroblasr

Question 12

megaloblast differences to a normoblast?

Answer 12

• It is larger than normal and shows nucleo-cytoplasmic dissociation, the cytoplasm is very mature but the nucleus is still quite primitive compared to what is appropriate

Question 13

2 forms of macrocytic anaemia? How to differentiate the two?

Answer 13

Megaloblastic anaemia
premature release of cells from the bone marrow

• Easily distinguished from megaloblastic macrocytic anaemia as that will have a low reticulocyte count

Question 14

Cause of megaloblastic anaemia

Answer 14

result of lacking vitB12 or folic acid

Question 15

Common population for megaloblastic anaemia

Answer 15

Elderly

Question 16

Common causes of macrocytic anaemia? (5)

Answer 16

• Megaloblastic anaemia as a result of lacking vitB12 or folic acid – not rare in the elderly
• Use of drugs interfering with DNA synthesis Often cancer drugs
• Liver disease and ethanol toxicity (most common cause)
• Recent major blood loss with adequate iron stores (reticulocytes increase)
• Haemolytic anaemia (reticulocytes increase)

Question 17

Normocytic anaemia mechanisms?

Answer 17

• Recent blood loss
• Failure of production of red cells
• Pooling of red cells in the spleen
• Can be due to early stages of micro/macrocytic anaemias

Question 18

Causes of normocytic anaemia? (3)

Answer 18

• Peptic ulcer, oesophageal varices, trauma (all of these cause blood loss)
• Failure of production of red cells:
  Early stages of iron deficiency or anaemia of chronic disease
  Renal failure – EPO drops
  Bone marrow failure or suppression Aplastic anaemia reduced number of red cells made by bone marrow, or bone marrow suppression by drugs e.g. for cancer
  Bone marrow infiltration Cancer
• Hypersplenism e.g. portal cirrhosis

Question 19

what is haemolytic anaemia

Answer 19

Anaemia resulting from shortened survival of red cells in the circulation

Question 20

2 ways of haemolysis occurring and how these are acquired

Answer 20

• Haemolysis can result from an intrinsic abnormality of the red cells (usually inherited and intrinsic)
• Haemolysis can result from extrinsic factors acting on normal red cells such as micro-organisms, chemicals or drugs that damage the red cell

Question 21

4 ways of classifying haemolytic anaemias

Answer 21

INHERITED or ACQUIRED

INTRAVASCULAR or EXTRAVASCULAR

Question 22

When does INTRAVASCULAR haemolysis occur

Answer 22

if there is a very acute damage to the red cell- the cells lyse within the circulation – hallmark is passage of haemoglobin within the urine. If you lyse cells within the circulation, haemoglobin binds to haptoglobin. Haemoglobin/haptoglobin complex is cleared by the liver and the body can conserve the iron, but if this occurs at such a rate the livewr is overwhelmed the haemoglobin is passed in the urine

Question 23

Hallmark of intravascular haemolysis

Answer 23

haemoglobin within the urine.

Question 24

Haemoglobin of cells lysed in the circulation binds to…

Answer 24

haptoglobin

Question 25

Haemoglobin/haptoglobin complex is cleared by ...

Answer 25

the liver

Question 26

When does EXTRAVASCULAR haemolysis occur

Answer 26

when defective red cells are removed by the spleen

Question 27

Sites of defects for inherited haemolytic anaemia (4)

Answer 27

abnormal Membrane, haemoglobin abnormal, defect in glycolytic pathway, defect in enzymes of pentose shunt (G6PD deficiency)

Question 28

Sites of defects for acquired haemolytic anaemia (3)

Answer 28

``` Membrane damage (autoimmune) Damage to whole red cell (mechanical, oxidant microbiological) ```

Question 29

Inherited and acquired kinds of damage to the RBC membrane?

Answer 29

Hereditary spherocytosis and autoimmune haemolytic anaemia

Question 30

Inherited defect to the RBC membrane?

Answer 30

Hereditary spherocytosis

Question 31

Inherited defect to the RBC haemoglobin?

Answer 31

Sickle cell anaemia

Question 32

Inherited defect to the pentose shunt?

Answer 32

G6PD deficiency

Question 33

Acquired damage to the RBC membrane?

Answer 33

Autoimmune haemolytic anaemia

Question 34

Acquired damage to the whole RBC - mechanical ?

Answer 34

Microangiopathic haemolytic anaemia

Question 35

MoA of inherited spherocytosis and how it causes EV haemolysis?

Answer 35

- After entering the circulation cells lose membrane in the spleen and thus become spherocytic - Red cells become less flexible and so are more likely to be trapped in splenic sinusoids and removed prematurely by the spleen-> EXTRAVASCULAR HAEMOLYSIS

Question 36

Bone marrow response to EV haemolysis and what does this cause?

Answer 36

- The bone marrow responds to haemolysis by an increase output of red cells leading to polychromasia and reticulocytosis - Leads to increased bilirubin production, jaundice and gallstones

Question 37

Treatment for hereditary spherocytosis

Answer 37

SPLENECTOMY

Question 38

What is the risk of a splenectomy

Answer 38

Leaves you prone to many blood infections

Question 39

What is the pentose phosphate shunt for

Answer 39

- Essential for the protection of the red cell from oxidant damage - Oxidants may be generated in the blood stream e.g. during infection, or may be exogenous If you have no G6PD you are at risk of haemolysis during infection or when oxidants are being produced

Question 40

G6PD causes what kind of RBC

Answer 40

IRREGULARLY CONTRACTED CELLS

Question 41

what happens to haemoglobin in G6PD deficiency

Answer 41

- Haemoglobin is denatured and forms round inclusions known as Heinz bodies These are removed by the spleen, leaving a defect in the cells

Question 42

Fix for acute haemolysis?

Answer 42

Blood transfusion

Question 43

What does production of autoantibodies directed at red cell antigens cause in the red cells

Answer 43

Spherocytosis and leads to removal of the cells from the circulation by the spleen EXTRAVASCULAR haemolysis

Question 44

how to diagnose AIHA (3)

Answer 44

- Spherocytes and increased reticulocyte count - Detecting immunoglobulin/complement on the red cell surface - Detecting antibodies to red cell antigens or other autoantibodies in the plasma

Question 45

Treatment for AIHA (2)

Answer 45

- Corticosteroids or other immunosuppressive drugs | - Splenectomy for severe cases