Blood Cell Abnormalities

Question 1

What is Leukaemia?

Answer 1

Bone marrow disease and overspill of the abnormal cells into the blood, producing white blood

Cancer that arises as a result of mutation in a precursor of myeloid or lymphoid cells

Question 2

What are the two terms used to show a greater or lesser degree of malignancy of Leukaemia?

Answer 2

Acute - If untreated, has profound pathological effects and leads to death in a matter of days

Chronic - causes less impairment of function of normal tissues and, although it will eventually lead to death, this usually does not occur for a number of years

Question 3

Why is it that the older a person is, the more likely they are to develop types of cancer?

Answer 3

Older a person is, more likely it is that enough spontaneous or induced mutations to have accumulated in a single cell for the cell to expand into a clone that replaces normal cells

Question 4

What are some examples of the abnormal behaviour of the leukaemic clone?

Answer 4

Growth without dependence on growth factors

Continued proliferation without maturation

Failure to undergo normal cell death

Question 5

What is the cause of Acute Myeloid Leukaemia (AML)?

Answer 5

Result of multiple sequential mutations - a consequence of exposure to environmental mutagenic influences that increase the rate of mutation considerably above natural baseline rate

sometimes irradiation or mutagenic drugs or chemicals (benzene, cigarette smoke)

Question 6

What is the cause of Acute Lymphoid Leukaemia (ALL)?

Answer 6

Due to events occurring during foetal development

Antigenic stimulation may also be a cause for development of types of ALL, leading to rearrangement of DNA so antibodies of greater affinity are produced

If process goes wrong, a lymphoid stem cell may acquire a malignant phenotype

Question 7

What are the differences in the causes of Acute and Chronic Leukaemia?

Answer 7

Acute - mutations in genes coding for transcription factors. So cells still proliferate so there is an accumulation of primitive (as they cannot mature) cells (blast cells) such as lymphoblasts or myeloblasts

Chronic - mutation involves activation of signalling, so the cells will still mature and interaction with stroma may lead to cell survival being prolonged. Impairment of physiological processes are therefore much less than in acute

Question 8

Give some of the direct effects of proliferation of the leukaemic cells

Answer 8

Bone pain

Enlarged spleen

Enlarged liver

Swollen lymph nodes

Question 9

Give the indirect effect of proliferation of the leukaemic cells

Answer 9

Replacement of normal bone marrow by leukaemic cells

Question 10

what are the clinical features?

Answer 10

fatigue, lethargy, pallor (anaemia)

fever and infections (neutropenia)

bruising and petechiae (thrombocytopenia)

bone pain (bone marrow expansion)

abdominal enlargement (hepatomegaly, splenomegaly)

lumps and swellings (lymphadenopathy)

Question 11

What mechanisms can lead to anaemia?

Answer 11

Reduced production of red blood cells by bone marrow

Loss of blood from body

Reduced survival of red cells in circulation (haemolysis)

Increased pooling of red cells in an enlarged spleen

Question 12

What is microcytic anaemia also known as?

Answer 12

Hypochromic anaemia

Question 13

What are the 3 common causes of microcytosis?

Answer 13

Iron deficiency anaemia - reduced synthesis of haem

Anaemia of chronic disease - reduced synthesis of haem

Thalassaemia - reduced synthesis of globin

Question 14

What are the 3 causes of iron deficiency?

Answer 14

Increased blood loss - Commonest cause in adults, could also be menstral

Insufficient intake - Dietary (vegetarians) or Malabsorption (Coeliac disease)

Increased requirements - Pregnancy or Infancy

Question 15

Describe the 3 stages of iron depletion

Answer 15

Iron depletion - Storage iron reduced or absent

Iron deficiency - Low serum iron & transferrin saturation

Iron deficiency anaemia - Low Hb and Hct

Question 16

Clinical features of iron deficiency anaemia

Answer 16

Pallor
Fatigue
Breathlessness
Failure to thrive
Impaired intellectual development in children

Question 17

What is Anaemia of Chronic Disease (ACD)?

Answer 17

Anaemia in patients who are unwell

There is usually an inflammatory aspect to the underlying disease

Question 18

Name some of the common causes of ACD

Answer 18

Rheumatoid arthritis - chronic inflammation can reduce the production of red blood cells in the blood

Autoimmune disease - AIHA, the body’s immune system attacks the red blood cells in error

Malignancy - RBCs wear out quickly and are not replaced as fast as they need to be

Kidney disease - Low Erythropoietin causes blood cell levels to drop, leading to anaemia

Infections such as TB or HIV - nutritional deficiency, malabsorption syndromes, failure of iron utilization, and bone marrow suppression

Question 19

How does Hepcidin regulate absorption of iron?

Answer 19

By inhibiting ferroportin, hepcidin prevents enterocytes from allowing iron into the hepatic portal system, thereby reducing dietary iron absorption

Iron is then lost when the enterocyte dies and is shed into the gut lumen

When iron stores (ferritin) are full, there is upregulation of hepcidin expression and iron absorption is limited

Whereas a requirement for increased erythropoiesis leads to a reduction in hepcidin and iron absorption is increased

Question 20

Give some of the laboratory clues of anaemia of chronic disease

Answer 20

C-Reactive Protein is high

Erythrocyte sedimentation rate (ESR) is high (unlike iron deficiency)

Ferritin is high

Transferrin is low

Acute phase proteins increase

Question 21

How can you distinguish between Iron Deficiency and Anaemia of Chronic Disease?

Answer 21

Ferritin is high in Anaemia of Chronic Disease

Transferrin is high in Iron Deficiency

Hb - Low, Low
MCV - Low, Low
Serum iron -  Low, Low
Ferritin - Low, High
Transferrin - High, Low

Question 22

How can Macrocytic Anaemia be assessed?

Answer 22

Examining blood film

Noting an elevated MCV

Question 23

Give some of the common causes for macrocytic anaemia

Answer 23

Lack of Vitamin B12 or Folic acid (megaloblastic anaemia)

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 24

What does it mean if there is an increased proportion of young red cells?

Answer 24

Young red cells are about 20% larger than mature red cells

So if there is an increased proportion of young red cells (Polychromasia/reticulocytes) in circulation, MCV will be increased

Question 25

What is a Megaloblast?

Answer 25

Abnormal bone marrow erythroblast

Larger than normal and shows nucleocytoplasmic dissociation

Question 26

What causes Megaloblastic Anaemia?

Answer 26

Deficiency of B12 or Folate

Question 27

What are the causes of Normocytic Anaemia, giving examples?

Answer 27

Recent blood loss - Gastrointestinal haemorrhage, trauma

Failure of production of red cells - Early iron deficiency, Bone marrow failure or suppression, Bone marrow infiltration

Pooling of red cells in the spleen - Hypersplenism, Splenic Sequestration in sickle cell anaemia

Question 28

When would you find a low reticulocyte count?

Answer 28

Reduced output of red cells from bone marrow

Question 29

What does reticulocyte count involve?

Answer 29

involves exposing living red cells to a dye (new methylene blue) that stains the higher RNA content of young red blood cells so that they can be counted

Question 30

What is ploychromasia?

Answer 30

cells have a blue tinge, caused by the ribosomal RNA in young red cells, in addition to the pink colour of the haemoglobin