10. Vitamin B12 Absorption Requires Two Binding
Proteins
ā¢ Vitamin B12 is absorbed
ā¢ Bound to intrinsic factor
ā¢ A small glycoprotein
ā¢ Secreted by the parietal cells of the
gastric mucosa
10
11. Vitamin B12 Absorption Requires Two
Binding Proteins
Gastric Acid And Pepsin
Release The Vitamin From
Protein Binding In Food
11
12. Vitamin B12 Absorption Requires Two
Binding Proteins
Bind To Cobalophilin
A Binding Protein
Secreted In The Saliva
12
13. Vitamin B12 Absorption Requires Two
Binding Proteins
In The Duodenum
Cobalophilin
Is
Hydrolyzed 13
14. Vitamin B12 Absorption Requires Two
Binding Proteins
Releasing The Vitamin
Bind To
Intrinsic Factor
14
15. Vitamin B12 Absorption Requires Two
Binding Proteins
Vitamin B12 Is Absorbed From The
Distal Third Of The Ileum
Via
Receptors
That Bind The Intrinsic Factor-vitamin
B12 Complex 15
16. Vitamin B12 Absorption Requires Two
Binding Proteins
Neither FREE INTRINSIC
FACTOR
NOR
FREE VITAMIN
IS ABSORBED
16
17. Vitamin B12 Absorption Requires Two
Binding Proteins
ā¢ INTO THE GENERAL
CIRCULATION
CARRIED BY
B12-BINDING PROTEINS.
17
18. Vitamin Bl2 combines with intrinsic
factor to form Vitamin B12- IF
complex.
Vitamin B12 intrinsic factor
complex is absorbed in the ileum.
In the illeal cells the intrinsic
factor is released and the B12 is
transferred to a plasma transport
protein transcobalamin II.
19.
20. Unlike other
water soluble
vitamins,
vitamin B12 is
stored in the
liver and other
tissues
Whole liver
contains about
4-5 mg of B12,
which is
sufficient for 2-
3 years.
he only water soluble vitamin stored
26. Methylmalonyl (COA)
Produced During The
Degradation of
Isoleucine, Valine, Threonine, And
Methionine
ā¢ AND
ā¢ Fatty Acids With Odd Numbers Of
Carbon Atoms
26
31. FUNCTIONS OF VIT B12
ā¢ WHEN THE VITAMIN IS DEFICIENT,
UNUSUAL FATTY ACIDS ACCUMULATE
ā¢ AND BECOME INCORPORATED INTO
CELL MEMBRANES, INCLUDING
THOSE OF THE NERVOUS SYSTEM
31
32. Vitamin B 12
COBALAMIN
KEY ROLE
ļ¼NORMAL FUNCTIONING OF
THE BRAIN AND NERVOUS
SYSTEM
ļ¼FORMATION OF BLOOD
ļ¼INVOLVED IN DNA
SYNTHESIS AND
REGULATION 32
33. Vitamin B 12
COBALAMIN
ļ¼FATTY ACID SYNTHESIS AND
ENERGY PRODUCTION
ā¢ ONLY BACTERIA HAVE THE
ENZYMES REQUIRED FOR ITS
SYNTHESIS
33
51. Folate trap hypothesis
The Levels Of The Other Forms
Decrease.
Cobalamin Deficiency Leads To
Deficiency Of The Other
Tetrahydrofolate Forms
Needed In Purine And TMP
Synthesis 51
53. VITAMIN B12 DEFICIENCY CAUSES
PERNICIOUS ANEMIA
ā¢ PATIENTS WHO FAIL TO ABSORB
THE VITAMIN FROM THE
INTESTINE.
ā¢ MOST OFTEN DUE TO REDUCED
SECRETION OF GASTRIC ACID
AND LESS EFFICIENT
ABSORPTION OF VITAMIN B12
FROM FOODS.
53
54. Pernicious Anemia
ā¢ AUTOIMMUNE DESTRUCTION
OF THE GASTRIC PARIETAL
CELLS
ā¢ RESPONSIBLE FOR THE
SYNTHESIS OF A
GLYCOPROTEIN CALLED
INTRINSIC FACTOR.
54
55. Pernicious Anemia
ā¢ LACK OF INTRINSIC
FACTOR PREVENTS THE
ABSORPTION OF VITAMIN
B12
ā¢ RESULTING IN
PERNICIOUS ANEMIA.
55
56. Pernicious Anemia
ā¢ PATIENTS WITH COBALAMIN
DEFICIENCY ARE USUALLY
ANEMIC, BUT LATER IN THE
DEVELOPMENT OF THE DISEASE
ā¢ THEY SHOW
NEUROPSYCHIATRIC SYMPTOMS
ā¢ CNS EFFECTS ARE
IRREVERSIBLE
56
58. Schilling test
ā¢ PHYSIOLOGIC BASIS BEHIND THE
SCHILLING TEST
ā¢ If you are able to absorb B12
normally,
ā¢ you will absorb it through your
intestinal cells
ā¢ it will enter bloodstream
ā¢ where it will circulate
throughout body 58
59. Schilling test
ā¢ If you canāt absorb it
correctly
ā¢ it will not be absorbed
through gut mucosa
ā¢ excreted in feces
59
60. Schilling test
ā¢ Saturate Any Open B12 Binding
Sites Throughout The Body
ā¢ The Patient Gets
Injections Of Regular B12 At The
Same Time
ā¢ Then we Use oral Radioactive B1260
61. In a patient who CAN absorb B12
properly, hereās what happens:
ļGive IM B12 To Saturate Any
Empty B12 Binding Sites
ļGive Patient A Drink Of
Radioactive B12
61
62. In a patient who CAN absorb B12
properly, hereās what happens:
Wait a while and see if the
B12 is absorbed through the
gut mucosal cells and
circulates around the body
in the blood
62
63. In a patient who CAN absorb B12
properly, hereās what happens:
It wonāt have many places to
drop off B12 (because youāve
thought ahead to block all those
sites) ā so most of the B12 will
just stay in the blood and get
excreted out in the urine
63
64. In a patient who CAN absorb B12
properly, hereās what happens:
ļYou measure the
radioactivity of the urine
ļ and that tells you how
much B12 made it through
the gut (was absorbed
through the gut) and got
into the blood
64
65. But in a patient who CANāT absorb
B12 properly, hereās what happens:
ā¢ Give IM B12 to saturate any
empty B12 binding sites
ā¢ Give patient a drink of
radioactive B12.
65
66. But in a patient who CANāT absorb
B12 properly, hereās what happens:
ā¢ Wait a while and see if the B12 is
absorbed through the gut mucosal cells
and gets into the blood
ā¢ If the patient canāt absorb B12, then
the B12 wonāt get through the gut
mucosal cells, and it will just stay in
the gut and excreted in the feces
(instead of in the urine)
66
67. Then ?
ā¢ Then, you can perform the test again, giving
the patient some intrinsic factor this time to
see if the B12 will be absorbed.
ā¢ If there is now radioactive B12 in the urine,
you know that the problem was lack of
intrinsic factor.
ā¢ If the urine still doesnāt have radioactive B12,
then you need to figure out some other cause.
67
70. Other Tests To Diagnose Pernicious
Anemia
ā¢Megaloblastic Anaemia
ā¢ Low levels of B12 in blood
ā¢Antibodies Against
ļ¼Intrinsic Factor
ļ¼Parietal Cells 70