Vit b12 deficiency causes and management

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Vitamin B12 Deficiency:Causes,
Manifestation and Management
Dr Jeetam singh
Jr 3 Internal medicine
MLN Medical college

Moderator:
Dr. Manoj Mathur(MD)
Assistant Professor
PG Department of Medicine
MLN Medical college

Synonyms
• Cyanocobalamine
• Anti Pernicious anemia factor
• Extrinsic factor of Castle

Structure
• Cobalamin is analogous to heme in its
structure having as its base a tetrapyrrole ring.
• Instead of iron as a...

Structure of Vitamin B12
oThe sixth position occupied by either a deoxyadenosine group, a methyl group or a
CN– group in t...

Forms of Cobalamin
• Cobalamin (vitamin B12) exists in a number of different
chemical forms.
• All have a cobalt atom at t...

Dietary Sources
• Cobalamin is synthesized solely by microorganisms.
• Ruminants obtain cobalamin from the foregut, but
th...

Dietary Sources of Vitamin B12

Requirements of vitamin B12
• A normal Western diet contains between
5 and 30 μg of cobalamin daily.
• Adult daily losses ...

RDA OF VITAMIN B12
• Age Male Female Pregnant Lactating
• 0-6months 0.4µg 0.4µg
• 7-12months 0.5µg 0.5µg
• 1-3 years 0.9µg...

Absorption
• Two mechanisms exist for cobalamin absorption.
• Passive absorption-occurring equally through
buccal, duodena...

Absorption
• Dietary cobalamin is released from protein
complexes by enzymes in the stomach,
duodenum, and jejunum
• It co...

Absorption and the role of Intrinsic
factor
• Intrinsic factor (IF) is produced in the gastric
parietal cells of the fundu...

Absorption of Vitamin B12 and the role of Intrinsic factor

Intrinsic factor deficiency
• In the absence of the intrinsic factor
inadequate amounts of cobalamin are
absorbed (the die...

Transportation of Cobalamin
• Three plasma transport proteins have been
identified.
• Transcobalamine I and III (differing...

Storage of Cobalamin
• The liver contains 2000 to 3000 mcg of stored
vitamin B12.
• Since daily losses are 1 to 3 mcg/day,...

Metabolic Role of Cobalamin
1)Cobalamin plays a vital role in the
catabolism of odd-chain fatty acids,
threonine, methioni...

Fate of Propionyl CoA

Fate of Propionyl CoA in B12
deficiency
• In cases of cobalamin deficiency these reactions of
utilization of propionyl co ...

2.Role of cobalamin in DNA synthesis and the
biochemical basis of Megaloblastic anemia
• The cause of megaloblastic anemia...

Implications of Inadequate
Thymidylate synthesis
• Inadequate dTMP restricts DNA but not RNA
synthesis leading to the appe...

3. Role of cobalamin in methionine
metabolism
• Cobalamin is required for the conversion of
homocysteine into methionine.
...

Role of Methionine
• Methionine help in formation of monoamine
neurotransmitter eg: Dopamine, Noradrenaline,
Serotonine.
•...

Folate trap
• In cobalamin deficiency, the methionine synthase reaction
cannot occur, N5-methyltetrahydrofolate accumulate...

Roles of cobalamin and folic acid in
methionine metabolism

Vitamin B12 deficiency
Level of vit B12 in blood
(ng/L)
Severity
160-200 to 1000 Normal
100 to 200 Borderline/Mild deficie...

Vitamin B12 deficiency
Causes of Vitamin B12 Deficiency
1. Nutritional Def.:
Dietary deficiency:- Vegan (rare)
2. Inherite...

B12 deficiency cause cont..
• Crohn’s disease.
• Tropical sprue and coeliac sprue.
• Ileal Surgical resection.
• Decreased...

B12 deficiency cont….

Manifestation:

Anemia
• Anemia is because of bone marrow suppression &
ineffective erythropoesis.
• Patient mostly presented with featur...

Neurological changes in B12
deficiency
1. Cerebrum:
 Complex neuropsychiatric symptoms: Delusion, illusion,
hallucinatio...

 Cardiovascular disease:
 Vit B12 deficiency lead to hyperhomocysteinemia which is
predispose to hypercoagulable state w...

 Other manifestation:
 Thrombocytopenia :- Petaechial rashes, easy bruising,
hemetemesis, malena, bleeding gums.
 Leuco...

Laboratory Findings
 The peripheral blood smear:
• It is usually strikingly abnormal, with anisocytosis and
poikilocytosi...

Peripheral blood smear in
Megaloblastic anemia
Blood film in vitamin B12deficiency showing macrocytic red
cells and a hype...

Laboratory Findings
 Bone marrow morphology :
• It is characteristically abnormal.
• Marked erythroid hyperplasia is pres...

Laboratory Findings
• Other laboratory abnormalities include
elevated serum lactate dehydrogenase (LDH)
and a modest incre...

Laboratory Findings
Serum cobalamin level: The diagnosis of vitamin
B12 deficiency is made by finding an abnormally
low v...

Laboratory Findings
Estimation of serum methylmalonic acid levels:
• In patients with coblamine deficiency sufficient to
...

• There is also increase level of Homocysteine in blood.
• The MMA and homocysteine level start rising even
before decreas...

Schilling test:
• Why the Schilling test is performed?
 The test can help to determine whether stomach is
producing “intr...

Procedure:
Stage 1:
 oral vitamin B12 plus intramuscular vitamin B12
• Oral dose: patient is given radiolabeled Vit B12 ...

 Stage 2: Vitamin B12 + IF If an Stage-I is abnormal:
• The test is repeated with additional oral intrinsic factor
• If t...

Stage 3: vitamin B12 and antibiotics:
• This stage is useful for identifying patients with
bacterial overgrowth syndrome....

Interpretation of schilling test

Differential Diagnosis
• Causes of macrocytic anemia:
 Vit B12 deficiency.
 Folic acid deficiency.
 Hypothyroidism.
 T...

Treatment of vitamin B12 deficiency
 The indications for starting cobalamin therapy are :
• A well-documented Megaloblast...

Treatment of vitamin B12 deficiency
• Patients with pernicious anemia have historically been
treated with parenteral thera...

Injection content Amount(per ml)
Vitcofol(10ml) Nicotinamide+folic acid+cyanocob. 200mg+15mg+500ug
Nurokind plus(2ml) Nico...

Sublingual tablets:

 Coblamin transdermal patches:
 Used once a day and a day in a week.
 Easy to use, better compliance but efficacy is li...

Questions

1. Macrocytic anaemia seen in all except:
a)Liver disease
b)Copper deficiency
c)Thiamine deficiency
d)Orotic aciduria

• Ans B
• Causes of Macrocytic anemia
1. Vit b12 def.
2. Folic acid def.
3. Orotic aciduria.
4.Nitrous oxide inhalation.
5...

2. Which of the following not found in vit b12 def.
a) Moeller’s glossitis
b) Sore tongue
c) Macroglossia
d) Atrophic glos...

• Ans. E
• Median rhomboid tongue:- This condition is
characterised by persistent erythematous, rhomboidal
depappilated le...

3. Megaloblastic anemia due to folic acid deficiency is
commonly due to:
a) Inadequate dietary intake.
b) Defective intest...

Ans.A

4. Megaloblastic anemia due to B12 def. is most
commonly due to:
a) Pernicious anemia
b) Defective intestinal absorption
c...

Ans. B

5. Which of the following is incorrect about pernicious
anemia
a) Lack of intrinsic factor
b) Peak age of onset is <20 yrs...

Ans. B Peak age of onset is 60 yrs.

6. All of the following is true about folic acid
prophylaxis except
a) It prevent NTD.
b) Folic acid prophylaxis prevent a...

Ans D

7.Which of the following incorrect about Imerslund’s
syndrome
a) Selective malabsorption of vit b12
b) Associated with pro...

Ans. D.
Imerslund’s syndrome/Imerslund-grasbeck
syndrome/congenital cobalamin malabsorption:
 This is autosomal recessive...

8. Megaloblastic anemia should be treated with both
folic acid and vit b12 because
a) It is a cofactor
b) It is enzyme
c) ...

• Ans. C
Megaloblastic anemia may be caused by a deficiency of
vit b12 or folate def. Unless it is clear that which of
two...

9. Cubilin receptor (receptor for IF-Cobalamin complex )
Found in all of the following except
a) Intestine
b) Yolk sac
c) ...

• Ans. Myelin sheath

10. 65 yrs old man present with anemia, tingling,
numbness, posterior column dysfunction which of
the following is likely ...

• Ans D
SACD:
 Condition of spinal cord characterised by demyelination of its neurons due to
deficiency of vit b12 which ...

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