micro + macrocytic anaemia Flashcards

1
Q

hypochromic microcytic anaemias

A

deficient haemoglobin synthesis, a cytoplasmic defect

something lacking in Hb synthesis -> nuclear machinery intact so cells keep dividing
- one of the signal to stop dividing is Hb accumulation
-> as a result the cells are small

and as they contain little Hb, they are hypochromic (lacking in colour)

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2
Q

causes of microcytic anaemia

A

TAILS
Thalassamia - globin
Anaemia of chrondisease - Fe (heme)
iron def - Fe (heme)
Lead poisoning - porphyrin
Sideroblastic anaemia - protoporphyrin (heme)

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3
Q

haem deficiency causes causing microcytic anaemia

A

lack of iron for erythropoiesis
- iron def
- AOCD - normal body iron but lack of available

problems with porphyrin synthesis
- lead poisoning
- congenital sideroblastic anaemias

(globin def = thalassaemia)

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4
Q

causes of macrocytic anaemia

A

megaloblastic anaemia
- B12 def
- folate def

normoblastic macrocytic anaemia
- alcohol
- reticulocytosis
- hypothyroidism
- liver disease
- drugs - azathioprine, methotrexate

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5
Q

megaloblastic

A

a larger than normal, nucleated red cell precursor, with an immature nucleus - usually based in the bone marrow

cytoplasmic development + Hb accumulation occur normally + so precursor cell is bigger with an immature nucleus
(stops replicating when reaches certain Hb content)

more apoptosis due to falty cells - big cells but less of them (anaemia)

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6
Q

causes of megaloblastic anaemia

A

B12 def (pernicious anaemia)
folate def

others - drugs, rare inherited stuff

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7
Q

treatment of megaloblastic anaemia

A

treat cause
- vit B12 injections (pernicious anaemia)
- folic acid tablets (5mg per day)

only if potentially lifethreatening anaemia - transfuse red cells

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8
Q

why are b12 + folate important?

A

essential co-factors in linked biochemical reactions which regulate -

  1. DNA synthesis + nuclear maturation - needed for conversion from uracil to thymine, def means too much uracil + initiating apoptosis
  2. DNA modification + gene activity - acts as a methyl donor to modify gene expression
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9
Q

blood film features of megaloblastic anaemia

A

hypersegemented neutrophils
pancytopenia

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10
Q

how is B12 absorbed?

A

intrinsic factor released by parietal cells in stomach forms a complex with B12 which is then absorbed in the distal ileum (end of small intest)

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11
Q

where does absorption of iron take place

A

occurs in duodenum + proximal jejunum (must be ferrous (Fe2+) state or bound to a protein such as heme

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12
Q

pernicious anaemia

A

autoimmune condition with resulting destruction of gastric parietal cells - results in intrinsic factor deficiency with B12 malaborption + deficiency

assoc with atrophic gastritis + history/FH of autoimmune disorders
symptoms often subtle - delayed diagnosis

other causes of b12 def - malnutrition, alcoholism

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13
Q

presentation of pernicious anaemia

A

Peripheral neuropathy with numbness or paraesthesia – “pins + needles”
Subacute combined degeneration of spinal cord – progressive weakness, ataxia, paresthesias
Loss of vibration sense or proprioception

Visual changes
- Mood or cognitive changes – memory loss, poor concentration, confusion, irritability
- Anaemia features – lethargy, pallor, dyspnoea

Mild jaundice – “lemon tinge” (combined with anaemia pallor)
Glossitis -sore tongue

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14
Q

pernicious anaemia investigations

A

testing for autoantibodies
- intrinsic factor antibody - 1st line
- gastic parietal cell antibody

(before)
FBC
- macrocytic anaemia (may be absent)
- hypersegmented polymorphs
- low WCC + platelets may also be seen

vit b12 + folate levels

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15
Q

management of pernicious anaemia

A

1mg IM vit B12 replacement (hydroxycobalamin) 3 times weekly for 2 weeks then every 3 months
- more intense regimes if neuro symptoms

if folate def too, treat B12 FIRST !!
- treating with folic acid with b12 def can lead to subacute combined degeneration of cord

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16
Q

folate absorption

A

dietary folates converted to monoglutamate
- absorbed in jejunum - diffusion + actively

17
Q

why can patients be jaundiced in pernicious anaemia?

A

B12 deficiency causes premature red cell destruction in the BONE MARROW

-> this results in excess bilirubin prodution

due to ineffective erythropoiesis
- red cells die prematurely in marrow
- Hb + lactate dehydrogenase (LDH) are released from dead red cells
- Hb converted to bilirubin

18
Q

causes of folate deficiency

A

inadequate intake - dietary more likely than b12 due to lesser stores - eg alcoholics
malabsorption - coeliac, crohns

excessive utilisation
- haemolysis, exfoliating dermatitis, pregnancy, malignancy

drugs - anticonvulsants !!!! know for exam**

19
Q

source, body store, site of absorption + daily requirement of b12

A

source = animal
body store = 2-4yrs (onset of def - years)
site of absorption = ileum
daily requirement = 1.5ug/day

20
Q

source, body store, site of absorption + daily requirement of folate

A

source = liver, leafy veg, fortified cereals
body store = 4months (onset of def quicker - weeks)
site of absorption = duodenum + jejunum
daily requirement = 200ug/day

21
Q

clinical features common to both b12 + folate deficiency

A

anaemia signs
weight loss
diarrhoea
infertility
sore tongue
jaundice !
developmental problems

22
Q

clinical features more assoc with b12 def

A

neurological problems
- posterior/dorsal column abnormalities - subacute degeneration of cord (can be assoc with irreversible neurological damage - early recognition important)

  • neuropathy
  • dementia
  • psychiatric manifestations
23
Q

why does a b12/folate deficiency present as pancytopenia?

A

b12/folate required for DNA synthesis (uracil -> thymine)

defective DNA synthesis in haematopoitic precursors affected, so all haematopoeic cells lines after are affected

(also maybe haemolysis of faulty cells?)

24
Q

blood findings in b12/folate deficiency

A

macrocytic anaemia
red cell count low
pancytopenia

blood film - macrovalocytes + hypersegmented neutrophils (neutrophils usually have 3-5segments)

autoantibodies
- antigastro-parietal cells - flaw sensitive not specific
- anti-intrinsic factor - flaw, specific not sensitive

25
Q

spurious/false macrocytosis

A

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

causes - reticulocytosis, cold-agglutinins

26
Q

causes of spurious/false macrocytosis

A

reticulocytosis
- an increase in reticulocyte number occurs as a marrrow response to acute blood loss or red cell breakdown (haemolysis)
- reticulocytes are bigger than mature red cells + are analysed along with these for the MCV measurement

cold-agglutinins
- clumps of agglutinated red cells are registered as 1 giant cell - increases MCV

27
Q

approach to investigating macrocytic anaemia

A

reticulocyte count
- raised - haemorrhage, haemolysis
- normal/decreased - blood film for hyperseg neutrophils

yes - serum b12/folate

no - liver disease, alcoholism, hypothyroidism - if no myelodysplasia, myeloma, aplastic anaemia -> bone marrow biopsy

28
Q

causes of normocytic anaemia

A

3As + 2Hs

acute blood loss
anaemia of chronic disease
aplastic anaemia

haemolytic anaemia
hypothyroidism

29
Q

what can cause a false anaemia?

A

haemodilution - excess fluid

30
Q

what is the core difference between microcytic + macrocytic? other than the size obvs

A

microcytic - haemoglobin problem

macrocytic - maturation problem