Endocrine/metabolic

Question 1

Absorption mechanism of Vitamin B12

Answer 1

Bound to ingested animal proteins - proteins denatures by acids and pepsin in stomach to release B12 -> B12 binds to haptocorrin to protect from B12 degradation - haptocorrin degraded by pancreatic enzymes in duodenum and B12 free again - binds to intrinsic factor travels to terminal ileum - B12/IF complext binds to IF receptor -> once absorbed binds to haptocorrin in blood (70-80%, inactive) and transcobalamin II (<30%, active)

Question 2

Function of vitamin b12

Answer 2

Important role in DNA synthesis and neurological function byt acting as a COFACTOR for 2 reactions:

1. MMA -> succinyl-CoA
2. homocysteine -> methionine (along with folic acid)

Question 3

Dietary sources of Vitamin B12

Answer 3

Animal products

• meat
• poultry
• fish!! (crab, clams, mussels esp. high levels)
• eggs
• dairy products (low levels)

Fortified foods including:

• soy milks
• vegetarian “meats”
• yeast spreads e.g. vegemite
• breakfast cereals

Question 4

Recommended daily intake of Vitamin B12

Answer 4

2.4mcg/day

85g of salmon

Question 5

Risk factors for B12 deficiency (8)

Answer 5

Vegetarian/vegan diet
Age >65y
Institutionalised/RACF residents
Newborns of vegetarian or malnourished mothers
Gastric surgery patients
Atrophic gastritis patients
H. Pylori infection
Patient with GI disorders (e.g. Crohn's, coeliac disease)

Question 6

Causes of Vit B12 deficiency

Answer 6

Nutritional:

• Low dairy/meat intake >65y
• alcoholism
• strict veganism

Increased requirements:
- pregnancy/lactation

Impaired absorption

• anti-intrinsic factor antibodies (i.e. Pernicious anaemia)
• autoantibodies to gastric parietal cells (atrophic body gastritis)
• gastrectomy
• prolonged use of PPI, metformin or H2RAs

Other GI causes:

• chronic GI symptoms
• coeliac disease
• Crohn’s
• intestinal surgery, gastric resection, sleeve or banding
• intestinal parasites
• ileocystoplasty

Question 7

Main medications known to lower Vit B12 levels

Answer 7

Histamine 2 receptor antagonists
Metformin (>4 months use)
PPIs (>12 months use)

Question 8

Clinical manifestations of Vit B12 deficiency

Answer 8

Haem:

• megaloblastic anaemia
• pancytopaenia
• pernicious anaemia

Neuro:

• paraesthesia
• peripheral neuropathy
• Combined systems disease

Psych:

• irritability, personality change
• mild memory impairment
• depression
• psychosis
• Alzheimer’s disease

CVS:
- ?increased risk of MI/Stroke

Question 9

Conditions causing falsely low serum vitamin B12 levels

Answer 9

Pregnancy
Primary folate deficiency
Iron deficiency
Inherited disorders of B12 metabolism
Oral contraception

Question 10

Management of B12 deficiency

Answer 10

To correct deficiency:
- hydroxocobalamin 1mg IM alternate days for 2 weeks (less intensive tx required if no anaemia or neuro symptoms)

Maintenance:

• if absorption not impaired: cyanocobalamin 50-200 microg/day orally, between meals
• if absorption impaired: hydroxocobalamin 1mg IM every 2-3 months

*iron supplementation may be required for patients with severe anaemia as iron stores will start to fall 1-2 days post first injection

Question 11

Recovery of symptoms after treatment of B12 deficiency

Answer 11

Hb will increase approx 10g/L per week, some symptoms will start to improve within 48h

Neuropathy improves more slowly, patients with long history of neurological symptoms may have residual effects