absorption and what goes wrong

Question 1

vitamins

Answer 1

organic compounds that required in small quantities for a variety of biochemical functions

Question 2

water soluble vitamins

Answer 2

• B complexes
• C or ascorbic acid

Question 3

fat soluble vitamins

Answer 3

• A or retinol
• D or cholecalciferol
• E or tocopherol
• K

Question 4

sources of vitamin B12 (cobalamin)

Answer 4

• synthesised solely by microorganisms
• only source for humans is - meat, fish, dairy products
• vegetables, fruits and other foods of non-animal origin are free from B12 unless contaminated by bacteria

Question 5

dietary requirement of vitamin B12

Answer 5

• western daily diet contains 5-30 microgram
• body stores2-5 milligram

Question 6

passive absorption of vitamin B12

Answer 6

• through buccal, duodenal and ileal mucosa
• rapid but extremely inefficient
• <1% of an oral dose is absorbed

Question 7

active transport of vitamin B12

Answer 7

• normal physiological mechanism is active transport
• occurs through ileum
• mediated by gastric intrinsic factor
• 70& of ingested amount is absorbed

Question 8

absorption of vitamin B12

Answer 8

• vitamin B12 is released from the food and bound to haptocorrin (transcobalamin I)
• haptocorrin is produced by salivary glands
• intrinsic factor (glycoprotein) is secreted by parietal cells
• haptocorrin is degraded in the duodenum releasing B12
• B12 is captured by intrinsic factor
• intrinsic factor-bound vitamin B12 is endocytosed by cubam in the terminal ileum
• inside the enterocyte intrinsic factor is degraded releasing B12
• ABC transporter releases B12 into the blood
• vitamin B12 binds to transcobalamin II

Question 9

plasma transport of vitamin B12

Answer 9

• vitamin B12 is transported in the plasma bound to transcobalamin I, II, III
• vitamin B12 bound to transcobalamin II is most important for cellular uptake
• internalisation occurs in complex with transcobalamin receptor (CD320) via endocytosis
• the transcobalamin is degraded releasing vitamin B12
• excess vitamin B12 is sent to liver for storage

Question 10

cellular role of vitamin B12

Answer 10

• essential co-enzyme for 2 enzymes in the body
• homocysteine –> methionine irreversible reaction first step
• tetrahydrofolate essential for DNA and RNA
• methylmalonyl-CoA mutase enzyme that require vitamin B12 found in mitochondria

Question 11

role of intrinsic factor in absorption

Answer 11

• produced in the parietal cells
• in the absence of intrinsic factor inadequate amounts of vitamin B12 are absorbed
• resulting in megaloblastic anaemia
• when due to absence of intrinsic factor it is pernicious anaemia

Question 12

pernicious anaemia

Answer 12

• autoimmune atrophic gastritis
• destruction of gastric parietal cells and lack of intrinsic factor
• immune response is directed against H/K/ATPase
• also causes achlorhydria (low production of gastric acid)
• can also be caused by antibodies against intrinsic factor

Question 13

aetiology of vitamin B12 deficiency

Answer 13

• inadequate dietary intake
• loss of gastric parietal cells or intrinsic factor
• functionally abnormal intrinsic factor
• bacterial overgrowth in intestine (stagnant loop syndrome)
• disorders of ileal mucosa (transcobalamin II deficiency)
• dysfunctional uptake and use of vitamin B12 by cells

Question 14

drug induced vitamin B12 deficiency

Answer 14

• proton pump inhibitors and H2 antagonists - reduction in stomach acid reduces separation of B12 from food)
• oral contraceptives and hormone replacement therapy - thought to be due to a reduction in transcobalamin
• metformin (reduces vitamin B12 absorption)
• colchicine (impairs or inhibits receptors in the terminal ileum)

Question 15

consequences of vitamin B12 deficiency

Answer 15

• normal serum concentration of vitamin B12 is 115-1000 mmol/L
• megaloblastic anaemia is the hallmark of symptomatic vitamin B12 deficiency
• in advanced causes anaemia may be severe with haematocrit as low as 10-15% (normal: 40% women; 45% men)
• may be accompanied by leucopoenia and thrombocytopaenia and hypersegemented neutrophils

Question 16

neurological symptoms of vitamin B12 deficiency

Answer 16

• paraesthesia (pins and needles) in hands and feet
• sensory loss
• gait ataxia
• weakness in legs
• subacute combined degeneration of spinal cord

Question 17

digestive symptoms of vitamin B12 deficiency

Answer 17

• hunter’s glossitis

Question 18

cardiovascular symptoms of vitamin B12 deficiency

Answer 18

• angina
• venous thromboembolic disease

Question 19

gynaecological symptoms of vitamin B12 deficiency

Answer 19

• infertility

Question 20

vitamin B12 derivatives

Answer 20

human serum has:
0-10% cyanocobalamin
8-15% hydroxocobalamin
22-39% deoxyadenosylcobalamin
36-62% methylcobalamin
- deoxyadenosylcobalamin and methylcobalamin are active forms of the vitamins in humans

Question 21

treatment of vitamin B12 deficiency

Answer 21

• oral cyanocobalamin and parenteral hydroxocobalamin
• must be parenteral in the case of gastric intrinsic factor deficiency (pernicious anaemia)
• lifelong treatment is necessary

Question 22

sources of vitamin B9 (folate/folic acid)

Answer 22

• dark green vegetables (broccoli, lettuce, brussels, sprouts, spinach)
• dried legumes (beans, lentils, chickpeas)
• fruits and fruit juices
• meat, seafood, poultry and eggs
• fortified cereals and bread

Question 23

recommended daily dose of vitamin B9

Answer 23

• 200 microgram
• 400 microgram during pregnancy

Question 24

absorption of folate

Answer 24

• natural folates are conjugated to a polyglutamyl chain
• folates are absorbed in the monoglutamate form
• hydrolysed by folypoly-y-glutamate carboxypeptidase
• N5-methyltetrahydrofolate (5-MTHF) is main dietary folate
• most absorption occurs in proximal small intestine (duodenum/jejunum) some absorption in colon
• folate is absorbed from the lumen by proton-coupled folate transporter (PCFT)
• absorption is also via a reduced folate carrier (RFC) with folate being exchanged for organic phosphate
• enterocytes have folate receptors
• folate can be exported without further metabolism or reduced to 5-MTHF
• both forms of folate are exported from enterocyte by an organic anion transporter

Question 25

plasma transport of folate and cellular uptake

Answer 25

• most is transported as monoglutamyl derivative
• most folate circulates free in the blood (some bound to albumin)
• plasma concentration is 10-30 nmol/L
• cellular uptake is by the same three mechanisms as for enterocytes (PCFT, RFC and folate receptor)
• intracellular folates exist primarily (75%) as polyglutamate conjugates

Question 26

aetiology of folate deficiency

Answer 26

• inadequate dietary intake
• congenital defects in the uptake system
• intestinal disease (coeliac, IBD, tropical sprue)
• drug interaction (cholestyramine, sulfasalazine, trimethoprim, methotrexate, metformin)
• chronic alcohol use
• increased cellular requirement (pregnancy)

Question 27

symptoms of folate deficiency

Answer 27

• sore tongue (glossitis) / pain upon swallowing
• nausea/vomiting
• abdominal pain
• diarrhoea
• cognitive impairment/dementia
• depression
• if severe results in megaloblastic anaemia

Question 28

treatment of folate deficiency

Answer 28

• oral folic acid for 1-4 months
• oral route is sufficient even in those with malabsorption
• treated until haematological recovery occurs