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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
What does a Shilling test comprise of?
- 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
Shilling test --> no B12 in urine --> why might this happen?
- not absorbing B12 (PA or s.bowl disease) | - hadn't corrected B12 deficiency before test
27
What is Pernicious Anaemia?
- autoimmune condition associated with severe lack of IF - you get very gradual development of anaemia * Peak age = 60 y/o * Family history
28
Folic acid is needed for a) b)
a) DNA synthesis | b) Homocysteine metabolism
29
in a normal RBC development:
- nucleus condenses down - cytoplasm becomes purple--> more pink --> red note: change in this = megaloblastic change
30
WHta is a characteristic cell that you might observe in patients with megaloblastic anaemia patients?
hypersegmented neutrophil
31
What 3 tests might you do if someone had macrocytosis?
- b12/folic acid test - liver function test - thyroid function test
32
What might hypersegmented neutrophil be a sign of?
b12 deficiency or folate deficiency
33
- note: homocysteine = kind of toxic so normally it is converted to methionine via B12
-
34
What is Romberg's sign? | What is it due to?
romberg's sign = loss of proprioception due to B12 deficiency
35
On examining B12 patient what might you see with regards to their reflexes?
- loss of reflex | - loss of plantar response
36
how might you treat someone with pernicious anaemia?
give injections of vitb12
37
What are the antibodies present in pernicious anaemia?
- anti IF antibodies | - anti parietal cell antibodies
38
note: Anti IF/parietal cell antibodies test only done if B12 deficiency has been confirmed
-
39
Why does hereditary spherocytosis cause haemolytic anaemia?
Due to extravascular haemolysis in the spleen
40
What causes haemolytic disease of the newborn (HDN)?
Anti-D crossing the placenta into an RhD positive foetus
41
What holds onto iron in the plasma?
Transferrin
42
Ferritin levels are a useful indicator of iron deficiency, but in which situation are they NOT ideal?
Raised CRP and ESR
43
How is B12 involved in DNA synthesis?
- B12 = needed to convert dUMP --> dTMP | - dTMP = important as a building block for DNA synthesis
44
How is folate + B12 deficiency treated?
- oral folate - oral cyanobalamin - parenteral hydroxycobalamin
45
who is at risk of DIETARY folate deficiency?
- elderly - sick - eating disorders - alcoholics
46
- B12/Folate deficiency = ROUND / OVAL macrocytes | - Liver disease and alcoholism = OVAL /ROUND macrocytes
- B12/Folate deficiency = OVAL macrocytes | - Liver disease and alcoholism = ROUND macrocytes
47
How is Folic acid absorbed?
- 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
B12 is a co factor in the conversion of _____ to ______
B12 is a co factor in the conversion of homocysteine to methionine

eMCD - Hae (11 decks)

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