Macrocytic Anaemia

Question 1

what is macrocytic anaemia?

Answer 1

red cells have a larger than normal volume

Question 2

what is false macrocytic anaemia?

Answer 2

the volume of mature red cell is normal, but the MCV is measured as high

Question 3

what are the two classifications of macrocytic anameia?

Answer 3

o Megaloblastic

o Non-megaloblastic

Question 4

what are the causes megaloblastic anaemia?

Answer 4

B12 Deficiency
Folate Deficiency
Others – drugs, rare inherited abnormalities

Question 5

what are the causes of non-megaloblastic anaemia?

Answer 5

Alcohol
Liver Disease
Hypothyroidism Marrow Failure – myelodysplasia, myeloma, aplastic anaemia

Question 6

what are the blood count features of macrocytic anaemia?

Answer 6

Hb (low), RBC (low), MCV (high)

Question 7

what are the blood count features of macrocytosis?

Answer 7

Hb (normal), RBC (normal), MCV (high)

Question 8

what are the features of macrocytic anaemia on blood film?

Answer 8

o >100fl

o Macrocytic red blood cells greater in size than nucleus of Lymphocyte

Question 9

what are the causes of normocytic anaemia?

Answer 9

1. Acute blood loss
2. Anaemia of chronic disease (or ↓MCV)
3. Bone marrow failure
4. Renal failure
5. Hypothyroidism (or ↑MCV)
6. Haemolysis (or ↑MCV)
7. Pregnancy

Question 10

what are the causes of megaloblastic anaemia?

Answer 10

B12/ Folate deficiency

– Drugs (hydroxycarbamide/ hydroxyurea

Question 11

what are the causes of Vit B12 deficiency anaemia?

Answer 11

Diet - vegan

Impaired absorption: Pernicious anaemia, Gastrectomy, illeal disease/resection, coeliac disease.

Question 12

what are the causes of pernicious anaemia?

Answer 12

Autoimmune condition where there is atrophy of the gastric mucosa, with failure of Intrinsic Factor (and acid production)→ B12↓ absorption.

Question 13

what are the causes of folate deficiency anaemia?

Answer 13

Poor Intake - old age, poverty, alcohol excess, anorexia
Malabsorption - coeliac, tropical sprue
Excess utilization
– pregnancy, lacatation, prematurity, chronic haemolytic anaemia, malignant and inflammatory diseases, dialysis

Question 14

what are the clinical features of megaloblastic anaemia?

Answer 14

Usually asymptomatic

Question 15

what are the clinical features of vit B12 deficiency anaemia?

Answer 15

Peripheral neuropathy – dorsal column degen.

Rarely – dementia

Question 16

what are the general clinical features of pernicious anaemia?

Answer 16

Glossitis, Angular stomatitis, Mild jaundice, weakness + tiredness, Dysponea, Diarrhoea, grey hair, Mild Splenomegaly, Fever

Question 17

what are the clinical features of folate deficiency anaemia?

Answer 17

Anaemia

Question 18

what is the management of Vit B12 deficiency anaemia?

Answer 18

Treat cause

IM B12 injections

Question 19

what is the management of pernicious anaemia?

Answer 19

IM Hydroxocobalamin

Question 20

what is the management of folate deficiency anaemia?

Answer 20

– Tx of underlying conditon.

– Oral folic acid 5mg daily for 4 months

Question 21

what is the pathophysiology of megaloblastic anaemia?

Answer 21

delayed nuclear maturation relative to that of the cytoplasm.

Question 22

what are the neurological clinical features of pernicious anaemia?

Answer 22

Polyneuropathy– weakness, ataxia, paraplegia

Optic atrophy – dementia, visual disturbances.

Question 23

what are the features on blood film of megaloblastic anaemia?

Answer 23

hypersegmented polymorphs (B12 ↓),

Question 24

what is the characteristic feature of pernicious anaemia?

Answer 24

Parietal cell antibodies 90%

IF antibodies 50%.

Question 25

what are the blood test features in pernicious anaemia?

Answer 25

``` – Hb ↓ – WCC + Platelets ↓ – Serum B12 ↓ < 50ng – Red cell folate ↓ – Serum Bilirubin ↑ ```

Question 26

what are the blood tests features for folate deficiency anaemia?

Answer 26

– Red cell folate ↓ | – Serum folate ↓

Question 27

what doe the red blood cells look like in megaloblastic anaemia?

Answer 27

abnormally large nucleated red cell precursor with an immature nucleus (primitive)

Question 28

what normally happens to erythroblast DNA?

Answer 28

stop diving and lose nucleus once Hb content is optimal

Question 29

what is the main mechanism of megaloblastic anameia?

Answer 29

defects in DNA synthesis and nuclear maturation but RNA and haemoglobin synthesis are preserved. Proerythroblasts expand but in maturing erythroblasts, division is reduced and apoptosis increases.

Question 30

what is the the process of megaloblastic cell formation?

Answer 30

* Cytoplasmic development and haemoglobin accumulation occur normally, and so the precursor cell is bigger with an immature nucleus, i.e. a ‘megaloblast’. * Once haemoglobin level in the cell is optimal, the nucleus is extruded, leaving behind a bigger-than-normal red cell

Question 31

what are the roles of B12 and folate?

Answer 31

Enable chemical reactions for  DNA synthesis  Gene activity

Question 32

what is the role of the folate cycle?

Answer 32

nucleoside synthesis (eg uridine to thymidine conversion).

Question 33

what is the role of the methionine cycle?

Answer 33

producing a methyl donor called ‘S-adenosyl methionine’ (impact on DNA, RNA, proteins, lipids, folate intermediates)

Question 34

what is the role of R protein?

Answer 34

Binds to B12 for transport

Question 35

what cells release intrinsic factor?

Answer 35

gastric cells in response to food

Question 36

what is the role of intrinsic factor?

Answer 36

Acid in stomach frees B12 which binds to intrinsic factor | bound form travels to terminal bowel to be absorbed

Question 37

what are the sources of B12?

Answer 37

animal

Question 38

what are the sources of folate?

Answer 38

liver, leafy veg, fortified cereals

Question 39

how long does the body store B12?

Answer 39

2-4 years

Question 40

how long does the body store Folate?

Answer 40

4 months

Question 41

where is B12 absorbed?

Answer 41

ileum

Question 42

where is folate absorbed?

Answer 42

duodenum and jejunum

Question 43

what is the daily requirement of B12?

Answer 43

1.5micrograms/day

Question 44

what is the daily requirement of folate?

Answer 44

200micrograms/day

Question 45

what are the causes of megaloblastic anaemia?

Answer 45

B12 Deficiency Folate Deficiency Others – drugs, rare inherited abnormalities

Question 46

what is the consequence of both vitB12 and folate deficiney?

Answer 46

microcytic anaemia (cancel each other out)

Question 47

what are the causes of B12 deficiency?

Answer 47

Diet – vegans Pancreas - Chronic pancreatitis Stomach – PA, Atrophic gastritis, PPIs/H2-receptor antganoists, Gastrectomy/Bypass Small Bowel - Jejunum: bacterial overgrowth, coeliac disease - Duodenum: resection, crohns disease Cubulin Receptors – inherited deficiency Pernicious Anaemia

Question 48

what are the causes of folate deficiency?

Answer 48

Inadequate intake - Malabsorption - Coeliac disease, Crohn’s disease Excess utilisation – Haemolysis, Exfoliating dermatitis, Pregnancy, Malignancy, Drugs, anticonvulsants

Question 49

what are the clinical features of megaloblastic anaemia?

Answer 49

o Symptoms/signs of anaemia o weight loss, diarrhoea, infertility o Sore tongue, jaundice o Developmental problems

Question 50

what symptoms are specific to vit B12 deficiency?

Answer 50

Neurological problems** – posterior/dorsal column abnormalities, neuropathy, dementia, psychiatric manifestations

Question 51

how is megaloblastic anaemia diagnosed?

Answer 51

``` FBC Blood film B12 and folate levels Autoantibodies Schillings test Bone Marrow Exam ```

Question 52

what will FBC in megaloblastic anaemia show?

Answer 52

low red cells | Sometimes pancytopenia

Question 53

What will the blood film in megaloblastic anaemia show?

Answer 53

macrovalocytes and hypersegmented neutrophils (3-5 nuclear segments)

Question 54

what is the management of megaloblastic anaemia?

Answer 54

Treat cause Vitamin B12 (hydroxycobalamin) injections for life in pernicious anaemia Folic acid tablets (5mg per day) orally