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ANKI GI > Vitamin B12 & Folate deficiency > Flashcards

Vitamin B12 & Folate deficiency Flashcards

1
Q

Which foods are rich in vitamin B12?

A

Dietary sources include animal and dairy products such as meat, poultry, milk, and eggs.

Stores of vitamin B12 in the liver remain in the body for years, so vitamin B12 deficiency depends on chronic, long-term deficiency.

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2
Q

What is the normal serum Vit B12 level?

A
  • <148 picomols/L (<200 picograms/mL) indicates probable deficiency,
  • 148 to 258 picomols/L (201-350 picograms/mL) indicates possible deficiency,
  • >258 picomols/L (>350 picograms/mL) indicates that deficiency is unlikely.

Vit B12 = cobalamin

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3
Q

Where is B12 absorbed?

A

Terminal ileum

(It is a water soluble vitamin)

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4
Q

What are the uses of vitamin B12 in the body?

A
  • DNA synthesis - cofactor
  • Integrity of nervous system - synthesis of myelin
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5
Q

How common is B12 deficiency?

A
  • Prevalence increases with age, and ranges from 5%-15% in older people
  • Nutritional deficiency of B12 is uncommon, but may be present in vegans and strict vegetarians who do not take supplements
  • Gastric bypass –> vit B12 deficiency
  • Common during pregnancy (levels decrease from 1st to 3rd trimester)
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6
Q

What is the aetiology of Vit B12 deficiency?

A
  • Decreased dietary intake
  • Diminished gastric breakdown of vitamin B12 from food
  • Malabsorption from the gastrointestinal tract.
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7
Q

Describe the absorption pathway of B12.

A
  • B12 is bound to food
  • It binds to R protein (haptocorrin) released in saliva and from parietal cells to prevent denaturation by stomach acid.
  • R protein is digested in duodenum
  • IF (intrinsic factor) is secreted by parietal cells and binds to VitB12. VitB12/IF complex is resistant to digestion. If no IF then no B12 absorption
  • This complex binds to cubilin receptor in distal ileum and enters cell. Complex is broken and B12 binds TCII (transcobalamin II) to cross basolateral membrane and travels to liver as VitB12/TCII complex (this is how is appears in plasma)
  • Proteolysis in liver breaks down TCII inside the cell.
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8
Q

Name 3 conditions which could cause Vit B12 malabsorption.

A
  • Crohn’s disease
  • Coeliac disease
  • Bacterial overgrowth syndromes- link between H pylori and B12 deficiency but it is unlcear whether organism or associated atrophic gastritis causes the deficiency.
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9
Q

Which medications can cause a B12 deficiency?

A
  • PPI
  • H2 receptor antagonists
  • Metformin
  • Anticonvulsants
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10
Q

What is pernicious anaemia?

A

Autoimmune destruction of the parietal cells (which produce intrinsic factor) which leads to reduced vitamin B12 absorption from the gastrointestinal tract

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11
Q

What type of anaemia can be caused by B12 or folate deficiency?

A

Macrocytic and megaloblastic anaemia

Picture below shows the link between B12 and folate in DNA synthesis. 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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12
Q

What are the risk factors for Vit B12 deficiency?

A
  • Age >65 - likely due to poor absorption
  • Gastric surgery - bypass or resection
  • Chronic GI disease
  • Vegan diet - if no supplements then up to 88% deficient
  • Metformin use - likely due to malabsorption
  • H2 receptor antagonist or PPI inhibitor use - B12 bound to food must be freed by peptic acid secretion from stomach.
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13
Q

What are the deficiency syndromes of B12?

A

Macrocytic anaemia

Neuropathy

Glossitis

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14
Q

What are the symptoms of B12 deficiency?

A

PARAESTHESIA - early and subtle symptoms of neurological damage

Difficulty walking, muscle weakness, visual impairment, psychiatric disturbance

Fatigue, lethargy, SOB (anaemia), pallor

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15
Q

What are the signs of B12 deficiency on examination?

A

B12 can cause posterior column degeneration which can lead to..

  • ataxia
  • decreased vibration sense
  • +ve Romberg’s sign (loss of proprioception)

Other:

  • Glosstis
  • Angular cheilitis
  • Petechiae
  • Pallor
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16
Q

What investigations should you do for B12 deficiency?

A
  • FBC- low Hct, high MCV
  • Blood smear - shows megalocytes, hypersegmented polymorphonuclear cells
  • Reticulocyte count -low index indicating low production, differentiates B12 from haemolytic anaemia(would be high)

Check for the cause of the deficiency:

  • Measure methylmalonic acid (MMA) - elevated, marker or B12 tissue deficiency
  • Homocysteine - elevated as above but not as specific for B12 deficiency
  • Antibodies to parietal cells and IF- positive in pernicious anaemia but antiparietal cell antibodies can be elevated in atrophic gastritis too

Other:

  • Antibodies for coeliac disease
  • Breath test for bacterial growth
  • Stool for H pylori
  • Test for giardia
  • Schilling test (no longer used)
17
Q

Which foods are rich in folate? How is folate in food reduced?

A

Green vegetables, legumes, and some fruits. Folic acid in cereal-grain products.

Folate is destroyed by overcooking/canning/processing

18
Q

Where is folate absorbed and what is the deficiency syndrome?

A

Jejunum

Macrocytic anaemia

Folate is AKA B9

19
Q

What is the classic manifestation of folate deficiency?

A

Megaloblastic anaemia without neuropathy is the classic manifestation of folate deficiency

20
Q

How common is folic acid deficiency?

A
  • Mainly affects pre-school children, pregnant women and elderly
  • Common in countreis without folic acid fortification of cereal-grain products - mandatory fortification was enforced in US in 1996 and Canada in 1998
  • Increases risk of neural tube defect pregnancies
21
Q

What is the function of folate in the body?

A

Required for

  • DNA synthesis
  • Homocysteine metabolism
22
Q

What type of anaemia is folate deficiency most commonly associated with?

A

Megaloblastic anaemia

23
Q

What is the aetiology of folate deficiency?

A
  1. INADEQUATE intake:
    • Eating unfortified cereals e.g. rice/wheat
    • Excessive cooking of veg
    • Malnutrition
    • Intake of special diets e.g. for phenylketonuria
    • Infant intake of goats’ milk (deficient in folate)
  2. Increased demand e.g. pregnancy, lactation, prematurity, chronic dialysis (causes loss)
  3. Malabsorption e.g. occurs in disorders of the small intestine, such as tropical sprue and coeliac disease and after extensive resection
24
Q

Name 2 neural tube defects caused by folate deficiency.

A

Spina bifida

Anencephaly

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

25
Q

What is the pathway of folate absorption in the body?

A
  • Polyglutamate form in food - chains of glutamic acid
  • It is polar and soluble in water so not absorbable in GI tract which has cells surrounded by lipid memranes
  • Therefore in jejunum it is broken down by enzymes from poly to mono-glutamate - this is smaller and less negatively charged so can pass into cells
  • There they are converted into THF by tetrahydrofolate reductase. These get methylated into methy-THF to leave the cell into the blood stream
  • This goes to liver to be stored for 2-3months but most is used in metabolic processes in cells
26
Q

What are the risk factors for folate deficiency?

A

IGNORANCE, POVERTY, APATHY

  • Low dietary folate intake
  • Age >65years
  • Alcoholism - if consuming more than 80g alcohol per day
  • Pregnant/lactating
  • Prematurity - RBC folate concentrations fall in first 2-3months in preterm infants whether breast fed or formula-fed so routine supplementation required
  • Intestinal malabsorption disorders
  • Medication - trimethoprim, methotrexate, sulfasalazine, pyrimethamine, anticonvulsants (eg. phenytoin, phenobarbital) - inhibit enzymes in folate metabolism
  • Infantile goat’s milk
  • Congetinal defects in folate absorption and metabolism

Increased cell turnover, intake of special diet, chronic dialysis.

27
Q

What are the signs and symptoms of folate deficiency?

A

Anaemia

  • Headache (megaloblastic anaemia) and dizziness
  • SOB
  • Pallor
  • Fatigue
  • Glossitis
  • Loss of appetite (due to megaloblastic anaemia)
  • Tahcycardia/tachypnoea/murmur/

Ischaemic heart disease and stroke

  • Signs of HF - displaced apical impusle, gallop rhythm, elevated JVP
  • Chest pain
  • Slurred speech
  • Paralysis

Pancytopenia

  • Anaemia - from low RBC
  • Recurrent infections - low WBC
  • Bleeding tendencies/petechiae - low platelets

Other: signs of alcoholism, exfoliative dermatitis

28
Q

What investigations would you do for folate deficiency?

A
  • FBC - low Hb, high MCV and MCH (but may be absent or less than expected); thrombocytopenia, neutropenia
  • Peripheral blood smear - macrocytosis, anisocytosis, poikilocytosis, hypersegmented neutrophils
  • Reticulocyte count - low corrected reticulocyte count indicating low production (present in other deficiency states and bone marrow failure)
  • Serum folate and RBC folate
  • Serum B12
  • Serum LDH - if high indicates ineffective erythropoiesis of advanced anaemia
  • Serum U Bilirubin - elevated if ineffective erythropoiesis in advanced anaemia
  • Iron panel - high serum iron, ferritin and transferrin as above
  • MMA - normal (high in B12)
  • Plasma homocysteine - elevated
  • Bone marrow aspirate/biopsy - megaloblastic changes, erythroid hyperplasia, abnormal nuclear appearance
29
Q

Why might you get premature vascular disease/atherosclerosis in folate deficiency?

A

It increases serum homocysteine levels which are associated with

  • Ÿatherosclerosis
  • Ÿpremature vascular disease

Mildly elevated levels of homocysteine are associated with:

  • Ÿcardiovascular disease DEFINITELY
  • Ÿarterial thrombosis PROBABLY
  • Ÿvenous thrombosis POSSIBLY
30
Q

Name 3 infections which may cause B12 deficiency.

A
  • H Pylori
  • Giardia
  • Fish tapeworm
  • Bacterial overgrowth

ANKI GI (43 decks)

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