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Haemotology > Macrocytic anaemia and vitamin B12 and folate > Flashcards

Macrocytic anaemia and vitamin B12 and folate Flashcards

1
Q

Macrocytic anaemia

A
  • Anaemias where the average red cell size is greater than normal (increased MCV)*
  • >100 fl*
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2
Q

types of maxcrocytic anaemia

A
  1. Megaloblastic anaemia
  2. Macronormoblastic erythropoiesis
  3. Stress erythropoiesis
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3
Q

causes of macrocytic anaemia

A
  • vitamin B12 anaemia
  • Folate deficiency
  • myelodysplasia
  • liver disease
  • alcohol toxicity
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4
Q

Megaloblastic anaemia

A
  • Interference with DNA synthesis during erythropoiesis causes development of nucleus to be retarded in relation to maturation of cytoplasm
  • Cell division delayed and erythroblasts continue to grow to form megaloblasts which give rise to larger red cells
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5
Q

causes of megaloblastic anaemia

A
  • Vitamin B12 / folate deficiency
  • Drugs that interfere with DNA synthesis (e.g. some anti- cancer)
  • Some erythroid leukaemias where DNA synthesis is retarded
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6
Q
A
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7
Q

Macronormoblastic erythropoiesis

A

Normal relationship between development of nucleus and cytoplasm is retained but erythroblasts are larger than normal and give rise to larger red cells

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8
Q

cause of macronormoblastic erythropoiesis

A
  • liver disease
  • alcohol toxicity
  • myelodysplastic syndrome
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9
Q

Stress erythropoiesis

A
  • Conditions associated with a high reticulocyte count (reticulocytes are larger than normal red cells)
  • High level of erythropoietin leads to an expanded and accelerated erythropoiesis
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10
Q

causes of stress erythropoiesis

A
  • Recovery from blood loss due to haemorrhage
  • Recovery from haemolytic anaemia
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11
Q

folate is the

A

synthetic form of folic acid

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12
Q

what synthesises folate

A

bacteria and plants

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13
Q

what are good sources of folate

A
  • Present in a wide variety of animal and vegetable food sources
    • Green leafy vegetables (foliage)
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14
Q

where is folate absorbed

A

duodenum and jejunum

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15
Q

once the folate has been absorbed in the duodenum and jejunum what is it converted to

A
  • tetrahydrofolate (FH4) by intestinal cells
  • Taken up by liver- store
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16
Q

importance of folate

A
  • Metabolic role to provide carbons for other reactions
    • E.g. synthesis of nucleotides bases required for DNA and RNA synthesis
17
Q

cause of folate deficiency

A
  • Dietary deficiency (poor diet)
  • Increased requirements
    • Pregnancy
    • Increased erythropoiesis e.g. haemolytic anaemia
    • Severe skin disease e.g. psoriasis
  • Disease of duodenum and jejunum (e.g. coeliac disease and crohns disease)
  • Drugs which inhibit dihydrofolate reductase e.g. methotrexate
  • Alcoholism
  • Urinary loss of folate in liver disease and heart failure
18
Q

symtoms of folate deficiency

A
  • Anaemia related
  • Reduced sense of taste
  • Diarrhoea
  • Numbness and tingling in feet and hands
  • Muscle weakness
  • Depression
19
Q

why is folic acid taken before conception and during the first 12 weeks of pregnancy

A

to prevent neural tube defects in babies e.g. spina bifida

20
Q

vitamin B12 is also known as

A

cyancobalamin

21
Q

what sort of vitamin is Vitamin B12 (cyanocobalamin)

A

Water soluble vit

22
Q

vitamin B12 is an

A
  • essential cofactor fo DNA synthesis (due to its role in folate metabolism)
  • required for normal eryhtropoiesis
  • essential for normal function and development of the CNS
23
Q

what produces vitamin B12

A

bacteria

24
Q

sources of B12

A
  • Largely obtained from foods of animal origin (produced by commensal bacteria)
    • Essential that people on a vegan diet eat foods fortified with B12 or take a B12 supplement daily or weekly
25
Q

vitamin B12 absorption

A
  1. B12 released from food proteins by proteolysis in stomach where it then binds to haptocorrin
  2. Haptocorrin B12 complex digested by pancreatic proteases in small intestine releasing B12 which then binds intrinsic factor (produced by gastric parietal cells).
  3. Intrinsic factor–B12 complex binds to cubam receptor which mediates uptake of complex by receptor- mediated endocytosis into enterocytes
  4. After lysosomal release in enterocytes, B12 exits via basolateral membrane through MDR1
  5. Binds to transcobalamin in blood and transported around bloodstream
  6. Majority of B12 is stored in the liver (store enough to provide B12 requirements for ~3-6 years)
26
Q

pernicious anaemia

A
  • Decreased or absent intrinsic factor (causes progressive exhaustion of B12 reserves
27
Q

cause of pernicious anaemia

A
  • Autoimmune disease
    • 2 types of antibody
      • Blocking Ab blocks binding of B12 to IF
      • Binding Ab prevents receptor mediated endocytosis
28
Q

causes of vitamin B12 deficeincy

A
  • Dietary deficiency
  • Lack of intrinsic factor (Pernicious anaemia)
  • Disease of the ileum (Crohns disease, ileal resection, tropical sprue)
  • Lack of transcobalamin (congenital defect)
  • Chemical inactivation of B12 e.g. frequent use of anaesthetic gas nitrous oxide
  • Parasitic infestation (tapeworm can trap b12)
  • Some drugs can chelate intrinsic factor (e.g. hypercholesterolaemia drug cholestyramine)
29
Q

symptoms of B12 deficiency

A
  • Anaemia related
  • Glossitis and mouth ulcers
  • Diarrhoea
  • Paraesthesia
  • Disturbed vision
  • irritability
30
Q

how can B12/folate deficiency also affect the NS

A
  • Folate deficiency in pregnancy can cause neural tube defects
  • Vitamin B12 deficiency associated with focal demyelination

Subacute combined degeneration of the cord

31
Q

B12 defiicency more often resuls in

A

reversible peripheral neuropathy

32
Q

which serious condition can B12 deficiency result in

A
  • subacute combined degeneration (irreversible) of the cord- involving degeneration of posterior and lateral columns of the spinal cord
33
Q

symptoms of subacute combined degeneration of the cord

A
  • Gradual onset weakness, numbness and tingling in arms, legs and trunk which progressively worsens
  • Changes in mental state
34
Q

relationship between B12 and Folate

A

lack of B12 will trap folate in the stable methyltetrahydrofolate form prveneting its use in other reactions such as synthesis of thymidine for DNA synthesis

35
Q

Why do B12 and folate deficiency cause a megaloblastic anaemia?

A
  • Both folate and B12 deficiency lead to thymidine deficiency
  • In absence of thymidine, uracil is incorporated into DNA instead
  • DNA repair enzymes detect these errors and constantly repair excision
  • Results in asynchronous maturation between nucleus and cytoplasm
    • Nucleus doesn’t fully mature
    • Cytoplasm matures at the normal rate
    • Large nuclei and open chromatin
    • Mature red cells also large leading to macrocytic anaemia
36
Q

megaloblastic features in peripheral blood film

A

As B12/foalte deficiency progresses a pancytopenia ca also develop i.e. low platelets and neutrophils as well

37
Q

Investigations for megaloblastic anaemia

A
38
Q

treatment of vitamien B12 and folate deficiency

A

Haemotology (12 decks)

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