Blood Cell Abnormalities

Question 1

What is leukaemia?

Answer 1

“White blood”

Bone marrow disease, overspill of abnormal cells into the blood

Arises as a result of mutation in a precursor of myeloid or lymphoid cells

Question 2

How is leukaemia classified?

Answer 2

Either myeloid or lymphoid

In this case myeloid includes not only granulocytes and monocytes but also megakaryocytes and erythroids

Question 3

Why is leukaemia slightly different from other types of cancer?

Answer 3

The abnormal cells circulate and spread

Therefore the concepts of local migration and metastasis are difficult to apply

The formation of localised tumour masses is also possible but not necessary

Malignant and benign are not used to describe leukaemias

Question 4

What terms are used instead of malignant and benign with leukaemia?

Answer 4

Acute and chronic

Depending on the degree of malignancy they shown

Acute : untreated, this would have a profound pathological effect and would cause a quick death

Chronic: less impairment of function of normal tissues. Will eventually lead to death

Determined by the nature of the mutation

Question 5

What are the fourain types of leukaemia given that there are two categories to consider?

Answer 5

Acute lymphoblastic leukaemia

Acute myeloid leukaemia

Chronic lymphocytic leukaemia

Chronic myeloid leukaemia

Question 6

Why does leukaemia occur?

Answer 6

A number of mutations in a primitive cell. Gives it a growth advantage

This single cell gives rise to a clone that slowly replaces normal cell

Mutations occur in oncogenes, and sometimes tumour surpressor genes

Question 7

Are mutations is germ cells (lead to gametes) beneficial or not?

Answer 7

They can be neutral, beneficial or harmful. Beneficial ones allow evolution

Question 8

Are mutations in somatic cells beneficial or harmful.

Answer 8

Very rarely beneficial. They are usually either neutral or harmful

Question 9

How do mutations in somatic cells occur?

Answer 9

Could be exposure to mutagens, or a random spontaneous process

The older the person, the more likely it is that enough spontaneous or induced mutations have occurred in a single cell for that cell to expand into a one that replaces normal cells

Question 10

What is some of the abnormal behaviour displayed by leukaemic clones?

Answer 10

Growth occurring without dependence on growth factors

Continued proliferation without maturation

Failure to undergo normal cell death (apoptosis)

Question 11

What causes acute lymphoblastic leukaemia?

Answer 11

Usually unowknown, sometimes mutagenic drugs, exposure to irradiation, exposure to chemicals in utero

Possibly delayed exposure to a common pathogen or pathogens

Question 12

What causes acute lymphoid leukaemia?

Answer 12

Ussually unknown, sometimes irradiation, mutagenic drugs or chemicals

(Benzene, cigarette smoke)

Question 13

What causes chronic myeloid leukaemia?

Answer 13

Usually unknown

Rarely irradiation or mutagenic drugs

Question 14

What causes chronic lymphoid leukaemia?

Answer 14

Unknown

Some families are predisposed

Question 15

What mutations result in acute leukaemias?

Answer 15

Mutations in genes encoding transcription factors with A resultant profound abnormality in the cells ability to mature. However the cells continue to proliferate so that there is an accumulation of primitive cells referred to as blast cells

Question 16

What mutations result in chronic leukaemias?

Answer 16

Activation of signalling pathways within the cell. Enables cells to proliferate without growth factors

However, maturation still occurs, so there is less loss of function than in acute leukaemia

Question 17

What are the signs and symptoms of leukaemia?

Answer 17

Direct - effects of the proliferation of leukaemic cells (bone pain, enlarged liver, enlarged spleen and swollen lymph nodes)

Indirect - effects of leukaemic cells which leads to a replacement of bone marrow cells (anemia, thrombocytopenia, neutropenia)

Question 18

What are the clinical signs of leukaemia?

Answer 18

Fatigue, lethargy, pallor (anemia)

Fever and infections (neutropenia)

Bruising and petechiae (thrombocytopenia)

Bone pain (bone marrow expansion)

Abdominal enlargement (splenomegaly, hepatomegaly)

Lumps and swellings (lymphadenopathy)

Question 19

What are essential investigations to diagnose leukaemia?

Answer 19

Full blood count and blood film

Flow cytometry, to characterise the profile of the cell surfacesrkers expressed

Cytogenetic/molecular genetic analysis

Question 20

What is anemia?

Answer 20

Reduction in the haemoglobin concentration in the circulating blood flow. Below healthy levels

Usually associated with a reduction in red blood cell count and haematocrit

Question 21

Which mechanisms result in anaemia?

Answer 21

Reduced production of RBCs by bone marrow

Loss of blood from the body

Reduced survival of red cells in circulation (haemolysis)

Increased pooling of red cells in an enlarged spleen

Question 22

Anaemia can also be classified by red blood cell size, what are the possibilities here?

Answer 22

Microcytic

Macrocytic

Normocytic

Question 23

What are some of the clinical studies causes of microcytic anaemia?

Answer 23

Iron deficiency (haem synthesis)

Anaemi of chronic disease (haem stnthesis)

Thalassaemia (globin synthesis)

(These cells are often also hupochromic)

Question 24

What is microcytic anaemia caused by?

Answer 24

Reduced synthesis of haemoglobin

Either reduces synthesis of haem (iron deficiency or chronic disease) or reduced synthesis of globin (thalassaemia)

Question 25

What causes iron deficiency anaemia?

Answer 25

Increased blood loss- hookworm is most common cause worldwide, also menorrhagia Insufficient intake - dietary (vegetarians), malabsorption (coeliac, H.pylori gastritis) Increased requirements - physiological (pregnancy, infancy)

Question 26

What are the stages of iron depletion?

Answer 26

Iron depletion - storage iron reduced or absent Iron deficiency - as above and low serum iron and transferrin saturation Iron deficiency anaemia - as above and low haematocrit and haemoglobin

Question 27

What are the clinical features of iron deficiency anaemia?

Answer 27

Pallor, fatigue, breathlessness Failure to thrive, impaired intellectual development in children ``` Koilonichia (spoon nails) Angular cheilitis (scabby mouth) ```

Question 28

What are some common causes of anaemia of chronic disease (ACD)?

Answer 28

Rheumatoid arthritis Autoimmune disease Malignancy Kidney disease Infections such as tuberculosis or HIV

Question 29

What are some laboratory clues for ACD?

Answer 29

High levels of C-reactive protein Erythrocyte sedimentation rate is high Ferritin is high Transferrin is low Acute phase proteins increase

Question 30

What happens in macrocytic anaemia?

Answer 30

Abnormal haemopoiesis so that the red cell precursors continue so synthesis haemoglobin and other cellular proteins but fail to divide normally One cause of macrocytic anaemia is megaloblastic erythropoiesis (delay in maturation of the nucleus while the cytoplasm continues to grow) Megaloblasts are generally seen in the bone marrow, not the blood film

Question 31

What are som common causes macrocytic anaemia?

Answer 31

Lack of vitamin B12 of folic acid Use of drugs interfering with DNA synthesis Liver disease and ethanol toxicity Recent major blood loss with adequate iron stores (reticulocytes increased) Haemolytic anaemia (reticulocytes increased)

Question 32

How is megaloblastic erythropoiesis detected?

Answer 32

(Megaloblast= abnormal bone marrow erythroblast) It is larger than normal and shows nucleocytoplasmic dissociation Possible to detect it from the peripheral blood, but to be sure requires bone marrow examination Blood film shows: tear drop cells, hyperseented neutrophils, oval macrocytes

Question 33

What mechanisms lead to normocytic anaemia?

Answer 33

Recent blood loss Failure to produce red blood cells Pooling of red cells in the spleen

Question 34

What causes normocytic anaemia?

Answer 34

Gastrointestinal haemorrhage, trauma Early stages of iron deficiency, bone marrow surpression. Bone marrow infiltration Hypersplenism

Question 35

How is the reticulocytes count done?

Answer 35

Expose living red cells to the dye methylene blue. Their higher RNA count means they show up bluer than older red blood cells