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YR2: MCD Haematology > Vitamin B12 and Folic Acid Deficiency > Flashcards

Vitamin B12 and Folic Acid Deficiency Flashcards

1
Q

What is vitamin B12 and what types of food is it commonly found in?

A

Cobalamin (vitamin B12) is a bacterial product that is ingested + stored by animals.
Found in meat, cheese, salmon, cod, milk, eggs

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2
Q

How much B12 is needed every day and how much is found in hepatic stores?

A

1.5-3 mcg/day required

Store: 2-5 mg (will last several years)

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3
Q

What is Vitamin B12 needed for?

A

DNA synthesis

Integrity of the nervous system (involved in myelination)

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4
Q

Broadly speaking, what can cause Vitamin B12 deficiency?

A 
Dietary deficiency (vegans) 
Decreased absorption
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5
Q

What types of food have lots of folic acid?

A

Leafy green vegetables

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6
Q

What can cause folic acid deficiency?

A

Dietary deficiency
Increased demand for folate
Impaired absorption

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7
Q

What is the dietary requirement of folic acid?

A

400-600 mcg

Run out of folate much quicker than B12

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8
Q

What is folic acid required for?

A 
DNA synthesis  
Homocysteine metabolism (potentially toxic)
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9
Q

Where does B12 absorption occur? What happens when it is in excess?

A

Small intestine
Stored
When stores saturated, excreted in urine

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10
Q

What are the 2 methods of B12 absorption?

A
  1. In duodenum, slow + inefficient

2. B12 must combine with intrinsic factor (made by parietal cells of stomach). B12-IF binds to ileal receptors

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11
Q

Deoxythymidine (dTMP) is a major building block of DNA synthesis. How is it produced?

A

Produced by methylation of deoxyuridine (dUMP)
For this to take place: need release of methyl groups from methyl-THF by the action of B12 as a cofactor accompanied by the conversion of homocysteine to methionine.

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12
Q

In what reaction is B12 a co-factor?

A

Conversion of homocysteine to methionine

Enzyme = methionine synthetase

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13
Q

State 6 clinical features of B12 and folate deficiency.

A 
Anaemia (macrocytic + megaloblastic) 
Jaundice (due to ineffective erythropoiesis) 
Angular Cheilosis  
Glossitis  
Sterility (in males) 
Weight loss + change of bowel habit
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14
Q

State 5 causes of macrocytic anaemia.

A 
Vitamin B12/ Folate deficiency 
Liver disease / alcoholism 
Hypothyroidism 
Drugs that interfere with DNA synthesis e.g. Azathioprine
Haematological disorders: 
Myelodysplasia
Aplastic anaemia
Reticulocytosis e.g. chronic haemolytic anaemia
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15
Q

How can you differentiate between the blood film of someone with B12/Folate deficiency and someone with liver disease or alcoholism causing macrocytosis?

A

B12/Folate deficiency = OVAL macrocytes (Megaloblastic)

Liver disease + alcoholism = ROUND macrocytes

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16
Q

What is a reticulocyte?

A

A young red blood cell with no nucleus

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17
Q

Describe how the appearances of cells of the red cell lineage change as they mature.

A

Become smaller + their cytoplasm becomes pinker

Nucleus starts off quite diffuse (open chromatin), becomes more + more compact until it is spit out

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18
Q

What 2 things do you look at when determining the maturity of a red blood cell?

A

Chromatin: how open is it?

Colour of the cytoplasm: how blue is it?

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19
Q

What is meant by ‘megaloblastic changes’?

A

Morphological changes in red cell precursors in the BM
Asynchronous maturation of the nucleus + cytoplasm.
Results in immature, open nucleus with mature cytoplasm.

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20
Q

Broadly speaking, what are megaloblastic changes the result of?

A

Defective DNA synthesis

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21
Q

Which of the causes of macrocytic anaemia also show megaloblastic changes in the bone marrow?

A

B12/Folate deficiency
Myelodysplasia
Drugs that interfere with DNA synthesis

22
Q

Describe the changes to red and white blood cells in megaloblastic anaemia

A

RBC’s:
Asynchrony between maturation of nucleus + cytoplasm
Large red cells
Anisocytosis
WBC’s:
Giant metamyelocytes (due to asynchronous maturation)
Hypersegmented neutrophils

23
Q

What may cause decreased intake of folate?

A

Ignorance, Poverty, Apathy

Elderly, Sick, Eating disorders, Alcoholics

24
Q

What are the consequences of folate deficiency for DNA synthesis?

A

Can’t methylate dUMP to dTMP, which affects DNA synthesis.

Also leads to the accumulation of homocysteine (can’t be converted to methionine)

25
Q

State 3 physiological and 3 pathological causes of increased folate demand.

A 
Physiological (increased growth):
Pregnancy
Adolescence 
Premature babies
Pathological (rapid cell turnover):
Malignancy 
Erythroderma (whole body rash)
Haemolytic anaemia
26
Q

State 3 causes of malabsorption of folate.

A

Coeliac Disease
Surgery or IBD (e.g. Crohn’s disease)
Drugs (e.g. colestyramine, sulfasalazine + methotrexate)

27
Q

State 3 tests to identify folate deficiency.

A

Full blood count
Blood film
Serum folate

28
Q

What would you expect the serum folate and red cell folate of a patient with B12 deficiency to be and why?

A

Serum folate = high
Red cell folate = LOW
Because B12 is required for folate to enter RBC’s

29
Q

What are the 3 main consequences of folate deficiency?

A

Megaloblastic anaemia
Neural tube defects in developing foetus
Increased risk of thrombosis in association with variant enzymes involved in homocysteine metabolism

30
Q

What are the2 types of neural tube defects?

A

Spinal cord = spina bifida

Brain = anencephaly

31
Q

What are the NICE guidelines for women to reduce risk of neural tube defects?

A

400 mcg folic acid preconception to 12 weeks gestation

32
Q

Homocysteine accumulates in folate deficiency. What are the consequences of this?

A

Very high homocysteine levels are associated independently with:
Atherosclerosis
Premature vascular disease
Mildly elevated homocysteine is associated with cardiovascular disease + probably with arterial + venous thrombosis.

33
Q

How did the FDA in the USA attempt to reduce the incidence of NTDs due to folate deficiency?

A

Fortify grain with folate

34
Q

Which groups of people are at particular risk of vitamin B12 deficiency due to decreased intake?

A

Vegans

35
Q

State 3 factors that can affect the absorption of B12.

A

AI: pernicious anaemia (severe lack of intrinsic factor)
Surgery: resection of parts of the GI tract
Inflammatory bowel conditions: Crohn’s, chronic pancreatitis, bacterial overgrowth, parasitic infection

36
Q

What are the 2 main consequences of B12 deficiency?

A

Macrocytic + megaloblastic anaemia
Neurological problems due to demyelination
Subacute combined degeneration of the spinal cord
Bilateral peripheral neuropathy
Optic atrophy
Dementia

37
Q

What may cause reduction in intrinsic factor leading to impaired B12 absorption?

A

Post-gastrectomy
Gastric atrophy
Antibodies to IF or parietal cells

38
Q

State 5 symptoms and signs of B12 deficiency.

A 
Symmetrical parasthesia
Muscle weakness 
Difficulty walking + loss of balance 
Visual impairment  
Psychiatric disturbance
39
Q

What is the role of B12 in DNA synthesis?

A

Both B12 and folate are needed for the production of dTMP (deoxythymidine), which is a crucial building block in DNA synthesis

40
Q

State 3 tests used to diagnose B12 deficiency.

A

Plasma homocysteine (high in B12 + folate deficiency)
Serum methylmalonic acid levels
Look for anti-IF antibodies

41
Q

What is the Schilling test for B12 absorption?

A

Give 2 capsules of B12 with different radioisotopes.
1 capsule will be B12 alone
1 capsule will be B12 + IF
Collect urine for 24 hours after administration + measure the presence + relative proportion of each isotope.

42
Q

What is pernicious anaemia and what does it result in?

A

Autoimmune condition associated with severe lack of IF
Males have decreased life expectancy
Increased risk of stomach cancer

43
Q

Which antibodies are found in pernicious anaemia?

A

Anti-IF antibodies (40-60% of adults with PA)

Anti-gastric parietal cell antibodies (80-90% of adults with PA)

44
Q

How is B12 deficiency treated?

A

Injections of B12 3x/week for 2 weeks then every 3 months

45
Q

Which cells are majorly affected in B12 and Folate deficiency?

A 
Rapidly dividing cells:
Bone marrow
Epithelial surface of mouth + gut
Gonads (spermatogenesis)
Embryonic
46
Q

How could B12 deficiency be indicated on examination?

A

Absent reflexes

Upgoing plantar responses

47
Q

What 3 things are essential for B12 absorption?

A

Intact stomach
Intrinsic factor
Functioning small intestine

48
Q

What 4 infections may cause B12 deficiency?

A

H Pylori
Giardia
Fish tapeworm
Bacterial overgrowth

49
Q

What 3 drugs are associated with low B12?

A

Metformin
PPI’s e.g. Omeprazole
Oral contraceptive pill

50
Q

What are the outcomes of the schilling test?

A
  1. Normal = excretion of radioactive b12 in urine
    No B12 in urine = Pernicious anaemia/ small bowel disease
  2. Pernicious anaemia: excretion of radioactive B12 (absorbed as given with IF)
    Small bowel disease: No B12 in urine

YR2: MCD Haematology (11 decks)

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