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eMCD - Hae > Haematology 9: Vitamin B12 and Folic acid Deficiency > Flashcards

Haematology 9: Vitamin B12 and Folic acid Deficiency Flashcards

1
Q

What is the role of B12 + folate in hemopoiesis?

A
  • required for DNA synthesis

- absence –> severe anaemia

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2
Q

B12 is required for:
1.
2.

A

B12 is required for:

  1. DNA synthesis
  2. Integrity of the nervous system
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3
Q

What is meant by megaloblastic?

What defines megaloblastic anaemia?

A

Megaloblastic = morphological change in RBC precursors within bone marrow

  • megalobastic anaemia = defined by
  • asynchronous maturation of nucleus + cytoplasm –> in erythroid series
  • maturing RBC seen in bone marrow
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4
Q

What are laboratory features of megaloblastic anaemia?

A
  • large RBC
  • anisocytosis (RBC unequal size)
  • hyperhsegmented neutrophils
  • giant metamyelocytes
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5
Q

What is meant by macrocytic?

A
  • average RBC = Above normal range
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6
Q

how is B12 absorbed?

A

initially:
- B12 binds to R protein (transcobalamin 1) in stomach
- Gastric pariental cells –> make intrinsic factor
- B12 leaves stomach –> duodenum
- pancreatic enzymes displace R protein from B12
- free B12 binds to intrinsic factor
- B12-IF couples –> goes to terminal ileum
- B12-IF complex = enters cell
- goes into portal circulation

In Circulation:
- B12 binds to Trancobalamin 2 –> Active B12

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7
Q

How is folate absorbed?

A
  • folate acid = hydrolysed to mono glutamates (at acid PH)
  • folate = absorbed as pteroglutamates
  • which can be methylated (in luminal cells) –> tetrahydrofolates.
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8
Q

What is meant by macrocytic anaemia?

A
  • Macrocytic: average RBC = Above normal range

-

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9
Q

list clinical features of folate + B12 deficiency

A
  • anaemia (macrocytic + megaloblastic)
  • jaundice
  • glossitis
  • angular cheilosis
  • weight loss, change of bowel habit (due to change in turn over of gut cells)
  • sterility
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10
Q

What are some causes of macrocytic anaemia?

A
  • Vit B12/ folate deficiency (oval macrocyte)
  • Liver disease / alcohol (round macrocytea)
  • hypothyroidism
  • drug e.g azathioprine
  • hematological disorders (eg myelodysplasia, asplastic anaemia, reticulocytosis)
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11
Q

What are some causes of macrocytic anaemia?

A
  • Vit B12/ folate deficiency (oval macrocyte)
  • Liver disease / alcohol (round macrocytea)
  • hypothyroid
  • drugs
  • hematological disorders
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12
Q

source of dietary folate=

- how is this destroyed?

A
  • fresh leafy vegetables

destroyed by overcooking/canning/processing

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13
Q

how would you do laboratory diagnosis of folate deficiency?

A
  • FBC + film

- Folate levels in the blood

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14
Q

List 3 consequences of folate deficiency:
1.
2.
3.

A

List 3 consequences of folate deficiency:

  1. Megaloblastic/macrocytic anaemia
  2. Neural tube defects in developing fetus
  3. Increased risk of thrombosis
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15
Q

What is the association between folic acid + homocysteine?

A

folate deficient = can’t convert homocysteine –>methionine

  • so homocysteine builds up (in plasma + intracellularly)
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16
Q

VERY HIGH homocysteine –> independently associated with:
1.
2.

A

VERY HIGH homocysteine –> independently associated with:

  1. Atherosclerosis
  2. Premature Vascular disease
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17
Q

VERY HIGH homocysteine –> independently associated with:

MILDLY elevated homocysteine –>

  1. DEFINATELY ______
  2. Probably _______
  3. Probably _______
A

VERY HIGH homocysteine –> independently associated with:

  1. Atherosclerosis
  2. Premature Vascular disease

MILDLY elevated homocysteine –>

  1. DEFINATELY cardiovascular disease
  2. Probably arterial thrombosis
  3. Probably venous thrombosis
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18
Q

What are some consequences of B12 deficiency?

A
  • neurological problems –> demyelination
  • optic atrophy
  • dementia
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19
Q

What might you see in an examination of a patient with B12 deficiency ? (in terms of reflexes)

A
  • absent reflexes + upping plantar responses.
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20
Q

What are some causes of B12 deficiency?

A
  • Poor absorption
  • reduced dietary intake
  • infections/ infestations
21
Q

Briefly describe the 2 ways of B12 absorption.

A
  1. slow + ineffeicient (in small intestine) 1%

2. B12 combine w IF –> then B12-IF complex binds to ill receptors (99%)

22
Q

What are 3 conditions for B12 absorption?

A

1 Intact stomach
2 Intrinsic factor
3 Functioning Small intestine

23
Q

Give some reasons why B12 absorption may be impaired.

A
  1. reduction in Intrinsic factor
    - Pernicious anaemia
    –> post gastrectomy
    –> gastric atrophy
    –> antibodies to IF or parietal cells produced
    (parietal cells where IF is made)
  2. Disease of Small bowel
24
Q

What are some drugs associated with Low B12 ?

A
  • metformin
  • omeprazole (H+ pump inhibitors)
  • Oral contraceptive pill
25
Q

What does a Shilling test comprise of?

A
  • drink radiolabelled B12
  • measure excretion in urine
  • repeat test with added Intrinsic factor
  • measure excretion in urine

If you’re NOT absorbing B12 –> then no B12 is detected in urine. It all goes into your poo!
so if you’re normal - you should be able to detect B12 in urine!

26
Q

Shilling test –> no B12 in urine –> why might this happen?

A
  • not absorbing B12 (PA or s.bowl disease)

- hadn’t corrected B12 deficiency before test

27
Q

What is Pernicious Anaemia?

A
  • autoimmune condition associated with severe lack of IF
  • you get very gradual development of anaemia
  • Peak age = 60 y/o
  • Family history
28
Q

Folic acid is needed for
a)
b)

A

a) DNA synthesis

b) Homocysteine metabolism

29
Q

in a normal RBC development:

A
  • nucleus condenses down
  • cytoplasm becomes purple–> more pink –> red

note: change in this = megaloblastic change

30
Q

WHta is a characteristic cell that you might observe in patients with megaloblastic anaemia patients?

A

hypersegmented neutrophil

31
Q

What 3 tests might you do if someone had macrocytosis?

A
  • b12/folic acid test
  • liver function test
  • thyroid function test
32
Q

What might hypersegmented neutrophil be a sign of?

A

b12 deficiency
or
folate deficiency

33
Q
  • note: homocysteine = kind of toxic so normally it is converted to methionine via B12
A

-

34
Q

What is Romberg’s sign?

What is it due to?

A

romberg’s sign = loss of proprioception due to B12 deficiency

35
Q

On examining B12 patient what might you see with regards to their reflexes?

A
  • loss of reflex

- loss of plantar response

36
Q

how might you treat someone with pernicious anaemia?

A

give injections of vitb12

37
Q

What are the antibodies present in pernicious anaemia?

A
  • anti IF antibodies

- anti parietal cell antibodies

38
Q

note: Anti IF/parietal cell antibodies test only done if B12 deficiency has been confirmed

A

-

39
Q

Why does hereditary spherocytosis cause haemolytic anaemia?

A

Due to extravascular haemolysis in the spleen

40
Q

What causes haemolytic disease of the newborn (HDN)?

A

Anti-D crossing the placenta into an RhD positive foetus

41
Q

What holds onto iron in the plasma?

A

Transferrin

42
Q

Ferritin levels are a useful indicator of iron deficiency, but in which situation are they NOT ideal?

A

Raised CRP and ESR

43
Q

How is B12 involved in DNA synthesis?

A
  • B12 = needed to convert dUMP –> dTMP

- dTMP = important as a building block for DNA synthesis

44
Q

How is folate + B12 deficiency treated?

A
  • oral folate
  • oral cyanobalamin
  • parenteral hydroxycobalamin
45
Q

who is at risk of DIETARY folate deficiency?

A
  • elderly
  • sick
  • eating disorders
  • alcoholics
46
Q
  • B12/Folate deficiency = ROUND / OVAL macrocytes

- Liver disease and alcoholism = OVAL /ROUND macrocytes

A
  • B12/Folate deficiency = OVAL macrocytes

- Liver disease and alcoholism = ROUND macrocytes

47
Q

How is Folic acid absorbed?

A
  • Folic acid enters GI tract as polyglutamates
  • Stomach acid hydrolyses polyglutamates –> monoglutamates
  • Folic acid = absorbed as pteroglutamates
  • Then it is methylated in the luminal cells –> to form methyl tetrahydroflorate
  • later on methyl tetrahydroflorate –> involved in converting homocysteine to methionine (through release of methyl groups)
48
Q

B12 is a co factor in the conversion of _____ to ______

A

B12 is a co factor in the conversion of homocysteine to methionine

eMCD - Hae (11 decks)

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