Lecture 14: Blood Cell Abnormalities

Question 1

What is anaemia?

Answer 1

Reduction in amount of haemoglobin in given volume of blood below expected comparison w/healthy subject of same age and gender.

Question 2

What are some mechanisms of anaemia?

Answer 2

• reduced production of red cells/haemoglobin in bone marrow
• loss of blood from body
• reduced survival of RBCs in circulation
• pooling of red cells in very large spleen

Question 3

What is a microcytic red cell?

Answer 3

A red cell that is smaller than normal

Question 4

What is a macrocytic red cell?

Answer 4

A red cell that is larger than normal

Question 5

What are some common causes of microcytic anaemia?

Answer 5

• defect in haem synthesis –> iron deficiency, anaemia of chronic disease
• defect in globin synthesis (thalassaemia)–> defect in a-chain or B-chain synthesis

Question 6

What are some causes of iron deficiency?

Answer 6

• Increased blood loss (menstrual, hookworm etc.)
• Insufficient intake (dietary, malabsorption - coeliac disease)
• Increased requirements (pregnancy, infancy, physiological)

Question 7

What is often another characteristic of microcytic red cells?

Answer 7

They are usually also hypochromic (paler)

Question 8

What can cause macrocytic anaemias?

Answer 8

Abnormal haemopoiesus so red cell precursors continue to synthesise haemoglobin and other cellular proteins but fail to divide normally

Red cells end up larger than normal

Question 9

What is a megaloblast?

Answer 9

An abnormal bone marrow erythroblast - larger than normal and shows nucleocytoplasmic dissociation

Question 10

What is megaloblastic anaemia caused by?

Answer 10

Deficiency of vitamin B12 or folate

Question 11

What are some causes of normocytic anaemia?

Answer 11

• gastrointestinal haemorrhage
• trauma
• early stages of iron deficiency
• bone marrow failure or suppression
• bone marrow infiltration
• hypersplenism
• splenic sequestration

Question 12

What is polycythaemia?

Answer 12

Too many red cells in circulation, increase in total volume

Question 13

What can cause polycythaemia?

Answer 13

• blood doping or overtransfusion
• appropriately increased erythropoietin e.g. as result of hypoxia
• inappropriate erythropoietin synthesis or use e.g. from renal tumour secretions
• independent of erythropoietin: polycythaemia Vera, intrinsic bone marrow disorder that leads to thick blood

Question 14

How should a blood count always be interpreted?

Answer 14

In context of clinical history and physical findings

Question 15

What is leukaemia?

Answer 15

Bone marrow disease

Question 16

What does leukaemia result from?

Answer 16

Series of mutations in single lymphoid or myeloid stem cell —> lead progeny of cell to show abnormalities in proliferation, differentiation or cell survival leading to study expansion of leukaemic clone.

Question 17

What is chronic leukaemia?

Answer 17

Leukaemia that behaves in a ‘benign’ manner

Question 18

What is acute leukaemia?

Answer 18

Leukaemia that behaves in a ‘malignant’ way, aggressive, patient dies quite rapidly

Question 19

What cells does lymphoid leukaemia affect?

Answer 19

B, T or NK cells/lineage

Question 20

What cells does myeloid leukaemia affect?

Answer 20

Any combination of granulocytic, moncytic, erythroid, megakaryocytic

Question 21

What are the 4 types of leukaemia?

Answer 21

• acute lymphoblastic leukaemia (ALL)
• acute myeloid leukaemia (AML)
• chronic lymphocytic leukaemia (CLL)
• chronic myeloid leukaemia (CML)

Question 22

What are some recognised leukaemogenic mutations?

Answer 22

• mutation in known proto-oncogene
• creation of novel gene e.g. chimaeric or fusion genes
• dysregulation of gene when translocation brings it under influence of promoter or enhancer of another gene

Question 23

Name some identifiable causes of leukaemogenic mutations.

Answer 23

• irradiation
• anti-cancer drugs
• cigarette smoking
• chemicals, benzene

Question 24

In AML, what happens as the cells continue to proliferate but no longer mature?

Answer 24

There is:

• a build up of most immature cells(myeloblasts or ‘blast cells’) in bone marrow which spreads into blood
• failure of production of normal functioning end cells such as neutrophils, monocytes, erythrocytes and platelets

Question 25

What do the mutations usually affect in AML?

Answer 25

• transcription factors
• product of oncogene prevents normal function of protein encoded by normal gene
• cell behaviour profoundly disturbed

Question 26

What do the mutations usually affect in CML?

Answer 26

Gene encoding a protein in signalling pathway between cell surface receptor and nucleus (protein may be membrane receptor or cytoplasmic protein)

Question 27

Are cell kinetics and functions more seriously affected in CML or AML?

Answer 27

AML

Question 28

What happens to cells in CML?

Answer 28

They become independent of external signals, alterations in interaction with stroma, reduced apoptosis so cells survive longer + leukaemic clone expands progressively

Question 29

In terms of end cells, what’s the difference between AML and CML?

Answer 29

AML = failure of production of end cells
CML = increased production of end cells

Question 30

What is ALL?

Answer 30

Acute lymphoblastic leukaemia which has an increase in very immature cells - lymphoblasts- with failure of these to develop into mature lymphocytes

Question 31

What is CLL?

Answer 31

Chronic lymphoid leukaemias - leukaemic cells are mature but are abnormal, T cells, B cells of NK cells

Question 32

What can accumulation of abnormal cells lead to?

Answer 32

• leucocytosis
• bone pain (acute)
• hepatomegaly
• splenomegaly (enlarged spleen)
• lymphadenopathy (lymphoid)
• thymic enlargement (if T lymphoid)
• skin infiltration

Question 33

What can lack of production of normal cells lead to?

Answer 33

Anaemia
Leucopenia
Thrombocytopenia