Anemia, Polycythemia and Leukaemia

Question 1

Define 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 happens to Hb concentration, RBC and PCV in anaemia?

Answer 2

All reduced

Question 3

What are the 4 mechanisms of anaemia?

Answer 3

1. Reduced production of red cells/ haemoglobin in the bone marrow.
2. Loss of blood from body (trauma).
3. Reduced survival of red cells in circulation.
4. Pooling of red cells in a very large spleen (hypersplenism, splenic sequestration).

Question 4

What can cause reduced synthesis of haemoglobin?

Answer 4

Reduced synthesis of haem e.g. iron deficiency

Reduced synthesis of globing e.g. thalassemia

Question 5

What is microcytic anemia and what are common causes?

Answer 5

Anemia in which the average cell size is decreased.

Caused by defect in haem synthesis or globin synthesis.

Question 6

3 causes of iron deficiency?

Answer 6

1. Blood loss (hookworm, menstruation)
2. Insufficient intake (vegetarians, malabsorption)
3. Increased requirements (pregnancy and infancy)

Question 7

What is macrocytic anemia and what are the 5 causes?

Answer 7

Anemia in which the average cell size is increased.

Causes:

1. B12 or folic acid deficiency (megaloblastic anemia)
2. Use of drugs interfering with DNA synthesis
3. Liver disease and ethanol toxicity
4. Recent major blood loss with adequate iron stores
5. Haemolytic anemia (reticulocytosis)

Question 8

Difference between polychromatic red cells and reticulocytes

Answer 8

Polychromatic = presence of red cells with a blue tinge to the cytoplasm.

Reticulocytosis = young cells recognised by a specific reticulocyte stain.

Question 9

What is polycythaemia and what are the 4 causes?

Answer 9

Too many red cells in circulation. Can be pseudo if plasma volume is temporarily reduced.

Causes:

1. Blood doping/ overtransfusion
2. Appropriately increased erythropoietin
3. Inappropriately increased erythropoietin
4. Independent of erythropoietin

Question 10

What is polycythaemia vera?

Answer 10

A myeloproliferative neoplasm which can lead to hyperviscosity of blood. This causes significant vascular obstruction.

Question 11

What is leukaemia?

Answer 11

Can bone marrow disease (not all patients have abnormal cells in the blood) due to a series of mutations in a single lymphoid or myeloid stem cell.

These mutations lead to the progeny of that cell to show abnormalities in proliferation, differentiation or cell survival.

Question 12

3 ways leukaemia is different from other cancers?

Answer 12

1. Normal haemopoietic stem cells can circulate in blood and both the stem cells and the cells derived from them can enter tissues.
2. Normal lymphoid stem cells recirculate between tissues and blood.
3. The concepts of invasion and metastasis cannot be applied to cells that normally travel around the body and enter tissues.

Question 13

What are the 3 known leukaemogenic mutations?

Answer 13

1. Mutation in a known proto-oncogene.
2. Creation of new gene (chimaeric or fusion)
3. Dysregulation of gene when translocation of the gene brings it under influence of the promoter or enhance of another gene.

Question 14

Difference between acute and chronic myeloid leukaemia

Answer 14

In AML:
1. Cells proliferate but no longer mature therefore failure to produce end cells.

2. Cell behaviour profoundly disturbed.
3. Mutations affect transcription factors.

In CML:
1. Mutations affect genes encoding signalling proteins between cell surface receptor and nucleus. Cell is independent of external signals.

Question 15

Difference between acute and chronic lymphoid leukaemia.

Answer 15

Acute - increase in very immature cells (lymphoblasts) with a failure of these to develop into mature lymphocytes.

Chronic - lymphocytes are mature but may be abnormal.

Question 16

What are the Disease characteristics of leukaemia?

Answer 16

Accumulations abnormal cells leading to:
Leucocytosis, bone pain, hepatomegaly, splenomegaly, lymphadenopathy (if lymphoid), thymic enlargement (if T lymphoid), skin infiltration

Lack of production of normal cells leading to:
Anemia, leukopenia, thrombocytopenia

Question 17

Cause and consequence of chronic myeloid leukaemia?

Answer 17

Translocation between chromosomes 9 and 22 in a haemopoietic stem cell produced a chimaeric gene which the cell a growth and survival advantage giving rise to a leukaemic clone. This leads to an increase in all granulocytes and their precursors.

There is also an enlarged spleen due to the chimaeric gene protein signals between cell surface and nucleus.

This can be inhibited by specific tyrosine kinase inhibitors.

Question 18

Cause and consequence of acute lymphoblastic leukaemia

Answer 18

•Leucocytosis with lymphoblasts in blood
•Anaemia
•Neutropenia
•Thrombocytopenia
•Replacement of normal bone marrow cells by lymphoblasts
Can be caused by:
1.Formation of a fusion gene
2.Dysregulation of a proto-oncogene by juxtaposition of it to the promoter of another gene e.g. a T-cell receptor gene
3.Point mutation in a proto-oncogene

Question 19

Treatment options

Answer 19

1. Supportive (provide red cells, platelets etc..)
2. Systemic chemo
3. Intrathecal chemo