10: Vit B12 & Folic acid deficiency Flashcards by David Park

Explain the role of vitamin B12 and folic acid in haemopoiesis and biochemical pathways

Recall dietary sources, mechanisms of absorption, and causes of deficiency

Explain the clinical features, haematological features,

Explain the diagnosis, investigation and management of these deficiencies

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What is B12 used for?

Required for DNA synthesis

Integrity of nervous system

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What is folic acid used for

Required for DNA synthesis

Homocystine metabolism

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What cells are affected in B12/Folate deficiency?

ALL rapidly dividing cells affected:
Bone marrow
Epithelia of mouth/gut
Gonads
Embryos

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Clinical features of B12/Folate deficiency?

Anaemia (weakness/fatigue)
Jaundice
Glossitis
Weight loss/change in bowel habit
Sterility (men)

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What type of anaemia would B12/Folate deficiency cause?

Macrocytic + megaloblastic

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Causes of macrocytic anaemia?

B12/Folate deficiency
Hypothyroid
Liver disease/alcohol
Drugs
Haem disorders (e.g. reticulocytosis)

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What tests would you do on a patient with macrocytic anaemia (high MCV)?

Check B12/Folate levels

2. Thyroid + liver function tests

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Define megaloblastic anaemia

Asynchronous maturation of nucleus + cytoplasm in the development of the erythroblast

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Characteristics of peripheral blood in megaloblastic anaemia

Anisocytosis
Large red cells
HYPERSEGMENTED neutrophils

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What can cause hypersegmented neutrophils?

Either B12 or Folate deficiency

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Dietary sources of folate?

Fresh leafy veg

Destroyed by overcooking, canning, processing

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What can increase folate demand?

Physiological: Preganancy, adolescence, premature babies

Pathological: Malignancy, erythroderma, haemolytic anaemia

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Consequences of folate deficiency

Megaloblastic macrocytic anaemia
Neural tube defects (spina bifida, anencephaly)
Increased risk of thrombosis

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When do you give folic acid to pregnant women?

0.4mg PRIOR to conception + first 12 weeks

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How does folate affect homocysteine?

Homocysteine = slightly toxic amino acid

Converted back to methionine by folate/B12

High levels of homocysteine are associated with?

Atherosclerosis

Premature vascular disease

Signs of B12 deficiency?

Tingling in fingers (paraesthesiae)
Muscle weakness
Difficulty walking
Visual impairment
Psychiatric disturbance
Glossitis
Loss of proprioception = Romberg's sign - Patient falls over if they close their eyes

Consequences of B12 deficiency

NEUROLOGICAL problems
Affects BOTH central and peripheral nerves

Bilateral peripheral neuropathy
Dementia
Optic atrophy
Subacute combined degeneration of the cord -> PARALYSIS

What would you find on examination of B12 deficiency?

NO peripheral reflexes (e.g. knee jerk)

NO upgoing plantar reflexes (e.g. tickling the foot)

Causes of B12 deficiency?

Poor absorption
Reduced dietary intake (B12 is found in animal produce)
Infections/infestations (rare)

Describe the normal absorption of B12

1% absorbed in duodenum (slow and inefficient)

MAIN METHOD:
Forms complex with Intrinsic factor (made by parietal cells in stomach)
B12-IF complex binds to ileal receptors in small intestine and get internalised

What 3 things are essential for normal B12 absorption?

Intact stomach (parietal cells) producing IF
Intrinsic factor
Functioning small intestine

What can cause reduced intrinsic factor levels?

Post-gastrectomy
Gastric atrophy
ANTIBODIES against IF or parietal cells (Pernicious anaemia)

What is pernicious anaemia?

- Autoimmune disease where you make anti-IF antibodies - Severe LACK of IF - Very GRADUAL onset of anaemia - Male patients have higher risk of stomach cancer

What are the types of antibodies made in PA?

1. IF antibodies | 2. Parietal cell antibodies (90% of PA cases)

What are diseases affecting the small bowel (terminal ileum)?

1. Crohn's disease (inflammatory) 2. Coeliac (autoimmune) 3. Surgical resection

Which infections can cause B12 deficiency?

H pylori Giardia Fish tapeworm Bacterial overgrowth

What drugs can cause B12 deficiency?

Metformin Proton pump inhibitors (e.g. omeprazole) Oral Contraceptive pill

What tests would you do to find cause of B12 deficiency?

1. Check antibodies for IF/parietal cells 2. Check antibodies for Coeliac disease 3. Breath test for bacterial overgrowth 4. Test stool for H pylori 5. Test for giardia

What is the shilling test?

1. Drink radiolabelled B12, measure excretion in urine 2. Repeat with added IF If B12 levels go back to normal with the addition of IF, that means you have PA

What does it mean if there is no B12 in urine?

1. NOT absorbing B12 (PA or small bowel disease) 2. Hadn't correct B12 deficiency before doing the test If someone has B12 deficiency, replenish their stores FIRST

If patient has all of the classic features of B12 deficiency but B12 levels are normal what do you do?

1. Measure methylmalonyl acid 2. Measure homocysteine 3. Look for anti-IF antibodies Treat as B12 deficiency until you get results back

Treatment of B12 deficiency

1. B12 injection 3 times a week for 2 weeks 2. After that, every 3 months IF neurological: Injections on alternate days until no further improvement (for up to 3 weeks) After that, every 2 months