Macrocytic anaemia

Question 1

What is the function of iron?

Answer 1

Creates haemoglobin

Question 2

What is MCV?

Answer 2

Size of the red blood cells

Question 3

What are the three categories of anaemia?

Answer 3

Microcytic (low MCV)
Normocytic (normal MCV)
Macrocytic (large MCV)

Question 4

There are 3 As and 2 Hs for normocytic anaemia

Answer 4

A – Acute blood loss
A – Anaemia of chronic disease
A – Aplastic anaemia
H – Haemolytic anaemia
H – Hypothyroidism

Question 5

Macrocytic anaemia can be _________ or _________

Answer 5

Macrocytic anaemia can be megaloblastic or normoblastic

Question 6

Megaloblastic anaemia results from..

Answer 6

Impaired DNA synthesis, preventing the cells from dividing normally. Rather than dividing, they grow into large, abnormal cells

Question 7

Megaloblastic anaemia is caused by..

Answer 7

Vitamin B12 deficiency
Folate deficiency
Secondary to methotrexate,anti-convulsants and sulphonylureas

Question 8

Normoblastic macrocytic anaemia is caused by..

Answer 8

Alcohol
Reticulocytosis
Hypothyroidism
Liver disease
Cytotoxics, azathioprine
Myelodysplasia
Pregnancy

Question 9

What causes Reticulocytosis?

Answer 9

Rapid turnover of red blood cells - haemolytic anaemia or blood loss

Question 10

Symptoms specific to iron deficiency anaemia include..

Answer 10

Pica
Hair loss

Question 11

What does the following clinical signs show?

Answer 11

Specific causes of anaemia

Also: atrophic glossitis, brittle hair and nails, jaundice, bone deformities, oedema, hypertension and excoriations

Question 12

Ix for anaemia

Answer 12

FBC, reticulocyte count, blood film, renal profile
LFT, ferritin, B12 and folate

Question 13

A ____________ and ____________ are indicated for unexplained iron deficiency anaemia to exclude gastrointestinal cancer as a source of bleeding

Answer 13

A colonoscopy and oesophagogastroduodenoscopy (OGD) are indicated for unexplained iron deficiency anaemia to exclude gastrointestinal cancer as a source of bleeding

Question 14

A _____________ is indicated for unexplained anaemia or possible malignancy (e.g., leukaemia or myeloma)

Answer 14

Bone marrow biopsy

Question 15

Modern analysers use the _____________ properties of red cells to measure the MCV

Answer 15

Light scatter

Question 16

What are the causes of
macrocytosis?

Answer 16

Megaloblastic
Non-megaloblastic

Question 17

Define Megaloblastic

Answer 17

A larger than normal, nucleated red cell precursor (‘mother cell’), with an immature nucleus

Question 18

What happens in megaloblastic anaemia?

Answer 18

Lack of red cells due to predominant defects in DNA synthesis and nuclear maturation in developing precursor cells in the marrow

Cell division is reduced and apoptosis increases

In surviving cells, Hb accumulation occur normally so precursor cell is bigger with an immature nucleus, i.e. a ‘megaloblast’

Once Hb level is optimal, the nucleus is removed, leaving behind a bigger-than-normal red cell, i.e. a ‘macrocyte’

Question 19

Causes of megaloblastic anaemia

Answer 19

B12 deficiency
Folate deficiency
Drugs and rare inherited abnormalities

Question 20

Why are B12 and folate important?

Answer 20

Regulates:

DNA synthesis and nuclear maturation - (e.g. blood cell effect)
DNA modification, gene activity – (e.g. nervous system)

Question 21

B12 deficiency may also affect lipid synthesis, impacting on..

Answer 21

Myelin (protective sheath around nerve fibres)

Question 22

What is pernicious anaemia?

Answer 22

Autoimmune disorder affecting the gastric mucosa that results in vitamin B12 deficiency

Question 23

Causes of pernicious anaemia

Answer 23

B12 deficiency
Atrophic gastritis (e.g. secondary to H. pylori infection), gastrectomy, malnutrition (e.g. alcoholism)

Question 24

Explain the pathophysiology of pernicious anaemia

Answer 24

Antibodies to intrinsic factor +/- gastric parietal cells, blocking the binding site
Reduced acid production and atrophic gastritis
Reduced intrinsic factor production → reduced vitamin B12 absorption

Question 25

Vitamin B12 is important in..

Answer 25

Production of blood cells and the myelination of nerves → megaloblastic anaemia and neuropathy

Question 26

Risk factors of pernicious anaemia

Answer 26

Middle to old aged females Autoimmune disorders: thyroid disease, type 1 diabetes mellitus, Addison's, rheumatoid and vitiligo A blood group

Question 27

Mild jaundice Glossitis (sore tongue) Pins and needles', numbness. Typically symmetrical and affects the legs more than the arms Memory loss, poor concentration, confusion, depression, irritabiltiy

Answer 27

Pernicious anaemia

Question 28

Ix for pernicious anaemia

Answer 28

FBC Vit B12 and folate Antibodies

Question 29

FBC checked in pernicious anaemia

Answer 29

Macrocytic anaemia: macrocytosis may be absent in around of 30% of patients Hypersegmented polymorphs Low WCC and platelets

Question 30

Vit B12 and folate in pernicious anaemia

Answer 30

Level of >200 nh/L is generally considered normal

Question 31

Antibodies checked in pernicious anaemia

Answer 31

Anti intrinsic factor: sensitivity is only 50% but specific for pernicious anaemia (95-100%) Anti gastric parietal cell: 90% but low specificity so often not useful clinically

Question 32

Mx for pernicious anaemia

Answer 32

Vitamin B12 replacement IM If no neuro sx: 3 injections per week for 2 weeks followed by 3 monthly If neuro sx: alternate days till improvement, then every 2 months Folic acid supplementation

Question 33

Complications of pernicious anaemia

Answer 33

Increased risk of gastric cancer

Question 34

Where is folate absorbed?

Answer 34

Jejunum (diffusion and actively)

Question 35

Causes of folate deficiency

Answer 35

Inadequate intake - alcoholic excess Malabsorption - coeliac disease, Crohn’s disease Haemolysis, exfoliating dermatitis, pregnancy, malignancy Anticonvulsants

Question 36

Where is B12 absorbed?

Answer 36

Ileum

Question 37

B12 sources

Answer 37

Animal

Question 38

Folate sources

Answer 38

Liver, leafy veg, fortified cereals

Question 39

Folate is absorbed in..

Answer 39

Jejunum

Question 40

Iron is absorbed in...

Answer 40

Duodenum/proximal jejunum

Question 41

B12 is absorbed in..

Answer 41

Ileum

Question 42

Megaloblasts vs Macrocytes

Answer 42

Megaloblasts are large nucleated RBC precursors with noncondensed chromatin due to impaired DNA synthesis Macrocytes are enlarged RBCs

Question 43

Pregnancy can be associated with low B12 levels, even if this does NOT reflect B12 deficiency. Why is that?

Answer 43

Functional B12 levels (25% of the B12 complex) remain normal, but levels of non-functional B12, called haptocorrin (75% of the B12 complex) fall. We do not measure these components separately and hence the total B12 (reflecting the greater contribution of haptocorrin to the measurement) is low

Question 44

Causes of B12 deficiency include..

Answer 44

Gasterctomy/bariatric surgery Terminal ileal disease (crohns, rarely TB) Ileal resection A vegan diet as B12 Bacterial overgrowth, acid suppression with a PP, coeliac

Question 45

The iron within enterocytes can either be stored as _______, or transferred into the bloodstream via the protein _______. Once in the blood, iron is bound to the transport protein _______

Answer 45

The iron within enterocytes can either be stored as ferritin, or transferred into the bloodstream via the protein ferroportin. Once in the blood, iron is bound to the transport protein transferrin

Question 46

Some iron is taken up by _________ in the reticuloendothelial system as a storage pool

Answer 46

Macrophages