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

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

Answer 3

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

Question 4

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

Answer 4

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 5

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

Answer 5

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 6

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

Answer 6

Bone pain

Enlarged spleen

Enlarged liver

Swollen lymph nodes

Question 7

• Give the indirect effect of proliferation of the leukaemic cells

Answer 7

Replacement of normal bone marrow by leukaemic cells

Question 8

What does the blood film of someone with AML look like

Answer 8

Blast cell has large size

Large Nuclei/cytoplasmic ratio

Cytoplasm contains granules consistent with those being myeloblasts and diagnosis of AML

Platelets and neutrophils notably absent, consistent with replacement of normal haematopoietic cells by leukaemia clone

Question 9

what are the clinical signs of someone with leukaemia

Answer 9

Fatigue

Pallor (anaemia)

Fever & infections (neutropenia)

Bruising & petechiae (thrombocytopenia)

Bone pain (bone marrow expansion)

Question 10

• What symptoms/signs may patient with CML present with?

Answer 10

Increase in all granulocytes (neutrophils, eosinophils, basophils) and their precursors - left shift

Abdominal discomfort (hepatomegaly, splenomegaly)

Question 11

What symptoms/signs may patient with CLL present with present with?

Answer 11

squashed CLL lymphocyte (smear)

Lumps and swellings (lymphadenopathy- swelling of lymph node)

Fatigue

Lethargy

Pallor (anaemia)

Question 12

what does the blood film of someone with ALL look like

Answer 12

Blast cells recognised by large size

High nuclei/cytoplasmic ratio

Open chromatin pattern of nuclei and prominent nucleoli

Cytoplasm has no granules (only difference from ALL)

Platelets and neutrophils are notably absent, consistent with replacement of normal haematopoietic cells by leukaemic clone

Question 13

What does someone with ALL present with

Answer 13

Lumps and swelling (lymphadenopathy)

Lethargy, pallor (anaemia)

Fever & infections (neutropenia)

Bruising and petechiae (thrombocytopenia)

Bone pain (bone marrow expansion)

Question 14

• What mechanisms can lead to anaemia?

Answer 14

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 15

• What are the 3 causes of iron deficiency?

Answer 15

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 16

• Describe the 3 stages of iron depletion

Answer 16

Iron depletion - Storage iron reduced or absent

Iron deficiency - Low serum iron & transferrin saturation

Iron deficiency anaemia - Low Hb and Hct

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

Question 22

• How can Macrocytic Anaemia be assessed?

- How does it occur?

Answer 22

Examining blood film
Noting an elevated MCV

abnormal haematopoiesis where red cell precursors continue to synthesise haemoglobin and other cellular proteins but fail to divide normally

Question 23

• What is a Megaloblast?

- what do macrocytic anaemias result from?

Answer 23

Abnormal bone marrow erythroblast
Larger than normal and shows nucleocytoplasmic dissociation
delay in maturation of nucleus but cytoplasm continues to mature and cell continues to grow

Question 24

• What are the causes of Normocytic Anaemia, giving examples?

Answer 24

Recent blood loss - Gastrointestinal haemorrhage, trauma

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

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

Question 25

• When would you find a high reticulocyte count?

- When would you find a low reticulocyte count?

Answer 25

In response to haemolytic anaemia
Recent blood loss

Reduced output of red cells from bone marrow

Question 26

How do cytokines in chronic disease affect erythropoietin production

Answer 26

cytokines eg TNF alpha and interleukins
decrease erythropoietin production
prevent normal flow of iron from duodenum to red blood cells