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Year 2 - MCD - Haematology > Vitamin B12 and Folic Acid Deficiency > Flashcards

Vitamin B12 and Folic Acid Deficiency Flashcards

1
Q

What are the roles of vitamin B12 and folic acid?

A
  • required for DNA synthesis

- Absence leads to severe anaemia which can be fatal

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2
Q

What is vitamin b12 needed for?

A
  • DNA synthesis

- integrity of the nervous system

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3
Q

What is folic acid needed for?

A
  • DNA synthesis

- Homocystine metabolism

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4
Q

How does b12 and folic acid deficiency show in terms of cell size?

A
  • typically high MCV
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5
Q

What is the link of b12 and folate in terms of DNA synthesis?

A

Both are needed for the production of deoxythymidine a crucial building block in DNA synthesis. As you can see here, deoxythymidine is made from deoxyuridine.

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6
Q

Which cells are affected by folate and b12 deficiency?

A
  • all rapidly dividing cells

- e.g. embryos, gonads, bone marrow, epithelial surfaces of mouth and gut

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7
Q

What are clinical features of folate and vitamin b12 deficiency?

A
  • Anemia: weak, tired, short of breath
  • Jaundice (because you are not making RBC enough and you are breaking RBCs down there is more bilirubin)
  • Glossitis and angular cheilosis (inflamed tongue and crackles in the corner of the mouth)
  • Weight loss, change of bowel habit
  • Sterility (interferes with spermatogenesis in males)
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8
Q

How do cells in b12 and folate deficiency appear?

A
  • megaloblastic

- macrocytic

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9
Q

What causes macrocytic anaemia?

A
  • Vitamin B12/folate deficiency
  • Liver disease or alcohol
  • Hypothyroid
  • Drugs e.g. azathioprine
  • Haematological disorders: Myelodysplasia, aplastic anemia, Reticulocytosis e.g. chronic haemolytic anemia
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10
Q

What does megaloblastic mean?

A

Describes a morphological change in the red cell precursors within the bone marrow

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11
Q

normal stages of red cell maturation?

A
  • erythroblast
  • normoblast: early, intermediate, late
  • reticulocyte
  • circulating RBC

(mature: no nucleus, just lots of Hb (red because of haem)
Proerythroblast has a nucleus and is making lots of proteins, nucleus dominates the cell.
To get from A to F you have to get rid of the nucleus.
Cytoplasm also changes -> it gets more and more pink because of haem synthesis rather than proteins and DNAnucleus gets more and more dense)

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12
Q

What is megaloblastic anaemia?

A
  • Defined by asynchronous maturation of the nucleus and cytoplasm in the erythroid series.
  • Maturing red cells seen in the bone marrow
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13
Q

What are the features of megaloblastic anaemia in peripheral blood?

A
  • Anisocytosis
  • Large red cells
  • Hypersegmented neutrophils
  • Giant metamyelocytes
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14
Q

What are hyper-segmented neutrophils?

A

more than 5 granule lobes

-> associated with megaloblastic change in the bone marrow

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15
Q

Q1. Thyroid disease can be a cause of megaloblastic red blood cells - true or false?

A

false

-> thyroid disease only causes macrocytosis NOT megaloblasticity.

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16
Q

Q2. Give 3 tests that you would do if someone had a macrocytosis

A 
Folate
Vit B12
Thyroid function test in anyone with a raised MCV
Liver function tests because 
Reticulocyte count
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17
Q

Q3: What are the underlying causes of hypersegme need neutrophils?

A
  • folate deficiency

- vitamin b12 deficiency

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18
Q

Facts about dietary folate

A
  • Fresh leafy vegetables
  • Destroyed by overcooking/canning/processing
  • in the US it is added to many foods in stores (e.g. grains fortified with folic acid)
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19
Q

What people are more likely to have folate deficiency?

A

Causes: apathy, poverty, ignorance

-> consider elderly and alcoholics (people that don’t really look after themselves)

Folate stores only last up to a few weeks.

(e.g. alcoholic admitted with a head injury after a fight
30y old lady with infected whole body eczema
90 y old lady who has a cup of tea and a jam sandwich for each meal)

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20
Q

When is there an increased demand in folate?

A

PHYSIOLOGICAL

  • Pregnancy
  • Adolescence
  • Premature babies

PATHOLOGICAL

  • Malignancy
  • Erythoderma
  • Haemolytic anaemias
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21
Q

How would you diagnose folate deficiency in the lab?

A
  • FBC and film (you might see raised MCV and megaloblastic changes)
  • Folate levels in the blood
  • also take a history and examine, look for skin conditions and ALD

assessing the cause:
EASY – history (diet/alcohol/illness)
EXAMINATION – skin disease/ alcoholic liver disease

22
Q

What are consequences of folate deficiency?

A
  • Megaloblastic, macrocytic anemia (mainly)
  • Neural tube defects in developing fetus (women should take folate supplements 3 months before trying to have a child)
  • Increased risk of thrombosis in association with variant enzymes involved in homocysteine metabolism
23
Q

What are examples of neural tube defects?

A
  • spina bifida
  • anencepahaly (born without a brain)

-> ALL PREGNANT WOMEN TAKE FOLIC ACID 0.4MG PRIOR TO CONCEPTION AND FOR FIRST 12 WEEKS

24
Q

What are highly elevated levels of homocysteine associated with?

A
  • atherosclerosis
  • premature vascular disease

-> very high rate of thrombosis

25
Q

What are mildly elevated levels of homocysteine associated with?

A
  • cardiovascular disease DEFINITELY
  • arterial thrombosis PROBABLY
  • venous thrombosis POSSIBLY (=less likely for venous thrombosis)
26
Q

What are consequences of B12 deficiency?

A

Neurological problems
- Bilateral peripheral neuropathy
- Subacute comined degeneration of the cord
- Posterior and pyramidal tracts of the spinal cord
- Optic atrophy
- dementia
(degeneration of cord also seen? severe)

27
Q

What might you see in a patient history with b12 deficiency?

A 
Paraesthesiae
Muscle weakness
Difficult walking
Visual impairment
Psychiatric disturbance
28
Q

What might you find upon examination of a patient with a b12 deficiency?

A

Absent reflexes and upgoing plantar responses

29
Q

What are causes of B12 deficiency?

A
  • poor absorption
  • reduced dietary intake (Stores are large and last for 3-4 years, Animal produce, Vegans are at risk)
  • infections/infestations (Abnormal bacterial flora (stagnant loops), Tropical sprue, Fish tapeworm)
30
Q

What can go wrong with the absorption of vitamin b12?

A
  • it is a complex process - many things can go wrong

-

31
Q

What can go wrong with the absorption of vitamin b12?

A
  • it is a complex process - many things can go wrong

- there can also be reduced absorption

32
Q

How is vitamin B12 absorbed?

A
  • a) in the duodenum (1% = slow and ineffective)
  • b) in the ileum after binding to IF which is made in parietal cells in the stomach -> b12-IF binds to ileal receptors (most absorption done this way)
  • after absorption, b12 is stored and once stores are filled it is excreted in the urine.
33
Q

What 3 things are essential in the absorption of b12?

A

Intact Stomach
Intrinsic factor
Functioning small intestine

34
Q

What causes a reduction in IF?

A

a) post gastrectomy
b) gastric atrophy
c) antibodies to intrinsic factor or parietal cells

35
Q

Pernicious Anemia

A

Autoimmune condition associated with SEVERE LACK OF IF

Peak age: 60 years
Family history
Males have a decreased life expectancy (increased risk of stomach cancer)

36
Q

Autoantibodies in PA?

A

= pernicious anemia

  • IF ABs (occasionally found in other conditions)
  • Pariteal cell ABs
    90% adults with PA
    16% normal females over age of 60
    Increased in relative of patients with PA

(a lot of us will have autoantibodies with age with no clinical significance)

37
Q

What are some diseases causing imputed b12 absorption?

A
  1. Diseases of small bowel (terminal ileum)
    a) Crohns
    b) Coeliac disease
    c) surgical resection
38
Q

What are some infections that may interfere with vitamin b12 absorption?

A

H Pylori
Giardia
Fish tapeworm
Bacterial overgrowth

39
Q

What are some drugs associated with vitamin b12 deficiency?

A

Metformin
Proton pump inhibitors e.g. omeprazole
Oral contraceptive pill

40
Q

What would you test for in patients with low b12?

A

What is the cause of B12 deficiency?

Antibodies to parietal cells and IF
Antibodies for coeliac disease
Breath test for bacterial overgrowth
Stool for H Pylori
Test for Giardia
OLDEN DAYS - Shilling test  (part I and part II)
41
Q

How does the schilling test work?

A
  • prior to the test you give vitamin b12and replenish the stores!!

a) drink radiolabelled B12
b) measure excretion in the urine

If there is a lot of radioactivity in the urine it has been absorbed because it ended up in the blood. If there is no radioactivity in the urine it was not absorbed
If there were no injections given, the B12 is soaked up and that the body vit b12 stores are full.

42
Q

Why is the shilling test not done anymore?

A

The company does not make it anymore and also because of the radioactivity

43
Q

Schilling test: what does the absence of b12 in the urine indicate?

A
  1. Not absorbing B 12
    • pernicious anaemia
    • small bowel disease
  2. Hadn’t corrected B 12 deficiency before the test

Normal = the radioactive b12 is in the urine because the stores in the body have been filled previously.

44
Q

What is the Schilling test part 2?

A

Repeat test but also give intrinsic factor this time and measure excretion in urine.

45
Q

What are the results of the Schilling test in pernicious anemia?

A

part 1: urinary excretion is low

part 2: urinary excretion is normal

antibodies are not alsways accurate in PA

46
Q

How do you treat PA?

A
  • lifelong b12 injections
47
Q

What would you do if a patient has low urinary excretion in both parts of the Schilling test?

A

Measure methylmalonyl acid
Measure homocysteine
Look for anti-intrinsic factor antibodies

Treat as B12 deficiency until you get all of the results back

48
Q

What would you do if a patient has a low urine excretion in schilling part 1 and a normal urine excretion in schilling part 2?

A

Sounds like PA -> give b12 injections

49
Q

Treatment of vitamin b12 deficiency

A
  • Injections of B12…. 1000ug (i.m)
    3x/week for 2 weeks
    Thereafter every 3 months
  • IF NEUROLOGICAL INVOLVMENT
    B12 injections alternate days until no further improvement – up to 3 weeks
    Thereafter every 2 months
  • Vegans should take b12 tablets
50
Q

A 49 y old man with grey hair and blue eyes presents with anaemia. His blood count is as follows:
Hb 90g/l WBC 4 x 109/l platelets 160 x 109/l MCV 110fl

Which would be the most appropriate set of investigations

a) Blood film, liver function, Shilling test
b) Folate, B12, thyroid function, liver function
c) Thyroid function, B12 and anti-intrinsic factor antibodies
d) Ferritin, shilling test, folate
e) Blood film, thyroid antibodies, anti-parietal cell antibodies

A

B) -> looks at causes of microcytic anemia

Year 2 - MCD - Haematology (11 decks)

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