Macrocytes and Macrocytic Anaemia Flashcards Preview

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Flashcards in Macrocytes and Macrocytic Anaemia Deck (44)
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1
Q

What is macrocytic anaemia?

A

Anaemia in which the red cells have a larger than normal size = measured using MCV

2
Q

How is MCV measured?

A

Using analysers = use light scatter properties

3
Q

When would a cell be classed as a macrocyte?

A

MVC > 100fl

4
Q

What are the types of macrocytosis?

A

Genuine = true increase in MCV

Spurious (also known as false)

5
Q

What are the categories of genuine macrocytosis?

A

Megaloblastic and non-megaloblastic

6
Q

What are normal red cell precursors called?

A

Erythroblasts or normoblasts = have a nucleus and are marrow-based

7
Q

What happens to normoblasts once they contain an adequate amount of Hb?

A

They stop dividing and lose their nucleus

8
Q

What characterises macrocytic anaemia?

A

Lack of red cells due to predominant defects in DNA synthesis and nuclear maturation in precursors

9
Q

What is a megaloblast?

A

Abnormally large nucleated red cell precursor with an immature nucleus

10
Q

What is abnormal about megaloblast maturation?

A

Division is reduced and apoptosis increases

11
Q

Why do megaloblasts end up bigger?

A

Immature nucleus prevents division plus cytoplasmic development and Hb accumulation are normal

12
Q

What happens once the Hb level in the megaloblast is optimal?

A

The nucleus is extruded to leave behind a macrocyte

13
Q

Why does macrocytosis cause anaemia?

A

Overall there are fewer cells despite the fact that they are bigger

14
Q

What are the cause of megaloblastic macrocytic anaemia?

A

B12 deficiency, folate deficiency, drugs, rare inherited abnormalities

15
Q

What processes do B12 and folate regulate?

A

DNA synthesis and nuclear maturation

DNA modification and gene activity

16
Q

How does B12 enter the body?

A

Enters in food and is released in the stomach by acid = binds to rapid binder protein from saliva as protection

17
Q

Where is intrinsic factor secreted from?

A

Gastric parietal cells = occurs in response to food in stomach

18
Q

What happens to intrinsic factor and B12-rapid binder complex once they leave the stomach?

A

Travel to duodenum = B12 is released from complex and binds to intrinsic factor

19
Q

Where does the intrinsic factor-B12 complex travel to once it leaves the small bowel?

A

Travels to distal small bowel where it attaches to receptors and enters the bloodstream = occurs in ileum

20
Q

What does the intrinsic factor-B12 complex bind to once it is in the bloodstream?

A

Transcohalamin receptors

21
Q

What are some causes of B12 deficiency?

A

Vegan diet, pernicious anaemia, atrophic gastritis, Coeliac, Crohn’s, bacterial overgrowth

22
Q

What is pernicious anaemia?

A

Autoimmune condition causing destruction of gastric parietal cells

23
Q

What does pernicious anaemia result in?

A

Intrinsic factor deficiency plus B12 malabsorption and deficiency

24
Q

How are folates absorbed?

A

Dietary folates converted to monoglutamate

Absorbed in jejunum

25
Q

What are the causes of folate deficiency?

A

Malabsorption = Crohn’s, Coeliac
Excess utilisation = haemolysis, exfoliating dermatitis, pregnancy, malignancy
Dietary insufficiency

26
Q

Why does folate deficiency present earlier than B12 deficiency?

A

Stores of folate

27
Q

What are some symptoms that occur in both folate and B12 deficiency?

A

Weight loss, diarrhoea, infertility, sore tongue, jaundice, developmental problems, signs of anaemia (e.g fatigue)

28
Q

What are some of the neurological conditions that occur in B12 deficiency?

A

Dorsal column abnormalities, neuropathy, dementia, psychiatric issues

29
Q

What is pancocytopenia?

A

Low number of all cells = can occur in some patients with B12 or folate deficiency

30
Q

How can B12 or folate deficiency be diagnosed?

A

Low red cell count = macrocytic anaemia
Blood film
Assay B12 and folate levels in serum

31
Q

What are the auto-antibodies associated with B12 and folate deficiency?

A

Anti-GPC and anti-IF auto-antibodies

32
Q

What does the blood film of a patient with B12 or folate deficiency show?

A

Macroovalocytes and hypersegmented neutrophils (more the 3-5 segments)

33
Q

How is megaloblastic macrocytic anaemia treated?

A

Vitamin B12 injections for life for pernicious anaemia
Folic acid 5mg oral tablets
Red cell transplant only if life threatening anaemia

34
Q

What are the causes of non-megaloblastic macrocytic anaemia?

A

Alcohol, liver disease and hypothyroidism = may not be associated with anaemia
Marrow failure = myelodysplasia, myeloma, aplastic anaemia (all cause anaemia)

35
Q

What is spurious macrocytosis?

A

Volume of mature red cell is normal but MCV is still measured as high

36
Q

What are the causes of spurious macrocytosis?

A

Reticulocytosis and cold-agglutinins

37
Q

What causes reticulocytosis?

A

Increase in reticulocyte numbers occurs as marrow response to acute blood or haemolysis

38
Q

Why does reticulocytosis cause a falsely high MCV and result in spurious macrocytosis?

A

Reticulocytes are bigger than mature red cells and are analysed alongside red cells for MCV measurement

39
Q

What are cold-agglutinins?

A

Proteins produced by cancers and infection

40
Q

How do cold-agglutinins cause spurious macrocytosis?

A

Cause clumping of red cells in samples at temperature <37 = falsely measured as one giant cell

41
Q

How can falsely high MCV measurements due to cold agglutinins be prevented?

A

Warm blood samples to 37 degrees

42
Q

What causes patients with pernicious anaemia to appear mildly jaundiced?

A

Intramedullary haemolysis = causes ineffective erythropoiesis

43
Q

How does ineffective erythropoiesis cause jaundice?

A

Red cells die prematurely in marrow
HB and LDH are released from dead red cells
Hb is converted to bilirubin

44
Q

How can pancytopenia complicate megaloblastic macrocytic anaemia?

A

Nuclear maturation defects can affect multiple lineages