Vitamin B12 deficiency is common in India, especially among vegetarians and the elderly. It causes hematological, neurological, gastrointestinal and vascular issues. The document discusses causes of B12 deficiency including pernicious anemia and intestinal malabsorption. Clinical manifestations and investigations for diagnosis are explained. Treatment involves lifelong B12 supplementation through injections or high dose oral supplements. Preventive measures for high risk groups like vegetarians and post-gastric surgery patients are also covered.

1. VITAMIN B12 DEFICIENCY IN
INDIA:
CLINICAL RELEVANCE AND
MANAGEMENT
BY
DR. YUGANDHAR. TUMMALA
1ST YEAR PG

2. INTRODUCTION
• Vitamin B12 or cobalamin is water soluble vitamin
synthesised by microorganisms and detected in foods of
animal origin.
• It is of 2 forms in human body.
• Methylcobalamin.
• 5-deoxyadenosil cobalamin.
• Functions of vitamin B12 are:
DNA synthesis.
Methylation.
Folate metabolism.
Erythropoiesis.
Neurodevelopment and Nervous system function.

3. • It is a co-factor for 2 enzymes:
Methionine synthase:
oIt is required for synthesis of amino acid, methionine from
homocysteine.
oSynthesis of S-adenosylmethionine(SAM), which is used for
methylation within DNA, RNA and proteins.
L-Methylmalonyl coenzyme A mutase.
• B12 deficiency is common in elderly patients.
• Low vitamin B12 with hyperchromocystinemia is common in
India and particularily in vegetarians.
• Deficiency of vitamin B12 shows Neuropsychiatric,
haematological and vascular manifestations.

4. ABSORPTION AND DISTRIBUTION
DIETARY
SOURCES:
Milk, Eggs, Fish and
meat.
IN STOMACH:
With the help of gastric
acid, found bound
cobalamin is released.
Binds to R-protein
(HC, cobalophilin)
that are produced in
salivary glands.
IN DUODENUM:
Cobalamin is released from
haptocorrin by pancreatic
protease and binds to IF to
form IF-Cbl complex.
IN TERMINAL ILEUM:
Receptors of enterocytes
recognises the IF-Cbl complex
and enters into cell.
INSIDE THE CELL:
IF is degraded into
lysosomes and Cbl is
released into blood stream
IN BLOOD STREAM:
Cobalamin binds to HC or TC
and facilitates the uptake of
cobalamin by cells.
IF-Cbl: Interleukin Factor
And Cobalamin
Complex.
HC: Haptocorrin.
TC: Transcobalamin.

5. CAUSES OF B12 DEFICIENCY
GASTRIC CAUSES:
Gastrectomy/Bariatric surgery.
Gastritis.
H. Pylori infection.
Due to all
these factors
Found bound vitamin B12
levels are reduced due to
decreased secretion of gastric
acid and enzymes (haptocorrin,
cobalophillin).
Diminished gastric function
also favours the bacterial
overgrowth in small intestine
and cause B12
malabsorption.

6. PERNICIOUS ANEMIA:
 It is the common cause.
 Occurs due to lack of intrinsic factor (IF).
 It is the autoimmune disorder called Polyglandular
Autoimmune Syndrome and can include disorders like
Autoimmune Thyroid Disease, Addison's Disease, Type 1 Diabetes
Mellitus, And Vitiligo.

7. Major conditions are:
Autoimmune Metaplastic Atrophic Gastritis
Autoantibodies directed against Hydrogen-potassium Adenosine
Triphosphatase (H-K-ATPase) in gastric parietal cells and
secretes hydrogen ions into the lumen in exchange for potassium.
Autoantibody Formation Against Intrinsic Factor Two
types of anti-IF antibodies: one that blocks the attachment of Cbl to
IF; and the other that blocks attachment of the Cbl-IF complex to
ileal receptors.
Gastric Tumors The chronic atrophic gastritis in PA is associated
with an increased risk of intestinal-type gastric cancer and of gastric
carcinoid tumors. Results in parietal cell loss, compensatory
hypergastrinemia, and argyrophilic cell hyperplasia.

8. INTESTINAL CAUSES:
Malabsorption: Factors that contribute are:
Gastric atrophy, achlorhydria.
Helicobacter pylori infection.
Intestinal bacterial overgrowth secondary to antibiotic
treatment.
Chronic alcoholism.
Gastric surgery/reconstruction for obesity (bariatric surgery).
Pancreatic exocrine failure.

9. Ileal Resection Or Bypass.
Crohn's disease.
Diphyllobothrium latum (fish tapeworm) infestation:
Transmitted by consumption of a variety of freshwater fish in a
raw form.
The diagnosis is generally established by identifying eggs or
proglottids in the stool and UGI scopy.

10. • DRUGS:
• Neomycin.
• Biguanides (eg, Metformin).
• Proton pump inhibitors (eg, Omeprazole).
• Histamine 2 receptor antagonists (eg, Cimetidine).
• N2O anesthesia which inhibits methionine synthase.
• HIV-INFECTION: Leads to
• Poor nutritional status.
• Diarrhea.
• Ileal dysfunction.
• Exudative enteropathy.

11. • Hereditary causes: Includes
• Decreased production of intrinsic factor.
• Decreased uptake of the intrinsic factor-cobalamin (IF-Cbl)
complex.
• It is due to mutation either in the gene for cubilin or "amnionless"
(AMN) receptor which is essential for ileal cobalamin uptake.
• Condition is called as Imerslund-Grasbeck syndrome or Juvenile
Megaloblastic anemia.

12. EPIDEMIOLOGY
• Epidemiological studies show that in general population, B12
deficiency has a prevalence of around 20%.
• Farmingham study revealed a prevalence of 12% among
elderly people.
• Other studies suggest that 30%—40% are at higher
prevalence,particularly elder people those who are
hospitalized and malnourished.

13. CLINICAL MANIFESTATIONS
• Hematological Manifestations.
• Neurological Manifestations.
• Gastrointestinal Manifestations.
• Hyperhomocystinemia And Vascular Manifestations.

14. •HEMATOLOGICAL MANIFESTATIONS:
Diminished activity of methionine synthase
deficiency
Inhibits the regeneration of tetrahydrofolate
(THF) resulting folate & B12 deficiency.
Impairment of DNA synthesis and affects the
rapidly dividing cells of bone marrow.
Results in Megaloblastic Anemia.

16. • Hematological features of Vitamin B12 are:
• Macrocytosis.
• Neutrophil hypersegmentation.
• Isolated thrombocytopenia.
• Neutropenia.
• Pancytopenia.
• Rarely:
• Hemolytic anemia.
• Thrombotic microangiopathy.

17. •NEUROLOGICAL MANIFESTATIONS:
oSubacute combined degeneration of the spinal
cord:
Also known as LICHTHEIM disease.
Degeneration of the posterior and lateral column of
the spinal cord.

18. Cbl deficiency leads to a defect in myelin
formation of unknown mechanism.
Leads to paresthesia and ataxia associated
with loss of vibration and position sense.
Progress to severe weakness, spasticity,
clonus, paraplegia, and even fecal and
urinary incontinence.
&

19. • Features include:
• Memory loss.
• Irritability.
• Dementia.
• Extrapyramidal signs like Tremors, Slurred speech, Akathesia,
Dystonia, Anxiety, Distress, Paranoia, and Bradyphrenia.
• Lhermitte's sign, a shock-like sensation that radiates to the feet
during neck flexion and/or a positive Romberg test.
• Optic neuropathy in those with Leber’s hereditary optic
neuropathy.
• Optic atrophy is a rare complication and may progress to visual
failure.

20. •GASTROINTESTINAL MANIFESTATIONS:
• Glossitis.
• Jaundice.
• Lactate dehydrogenase.
• Elevated levels of bilirubin.
• Abdominal pain, Nausea, Vomitings, Diarrhoea, Loss of
Apetite.
• Mucocutaneous ulcers.

21. •HYPERHOMOCYSTINEMIA AND VASCULAR
MANIFESTATIONS:
Deficiency of B12 and folic acid leads
to Hyperhomocystinemia.
Leads to Loss Of Elasticity of blood
vessels that leads to damage of intima.
This damage leads to cholesterol, collagen
and calcium to build up, causing Plaque
Formation.
Leads to Myocardial Infarction,
Stroke, Pulmonary Embolism, DVT

22. • The Amount Of Homocysteine Is Regulated By Three
Vitamins:
• Folate.
• Vitamin B6.
• Vitamin B12.

23. •SKELETAL MANIFESTATIONS:
As B12 deficiency leads to high Homocysteine
levels.
Homocysteine binds to collagenous matrix of
bone.
Modifies collagen properties and reduce bone
strength.
Leads to Osteoporosis due to alterations in
bone biochemical properties.
Leads to increase the risk of fractures. (Elderly
people are more prone).

24. INVESTIGATIONS
•Macroovalocytic Anemia:
• Hypersegmented Neutrophils.
• Elevated iron levels.
• Elevated levels of indirect bilirubin.
• Low levels of haptoglobin.
• Increased red cell breakdown.
• Normal reticulocyte count.
• Thrombocytopenia, Neutropenia, Pancytopenia when anemia is severe. These
suggest diagnosis such as myelodysplastic syndrome/acute myeloid
leukemia (MDS/AML), or aplastic anemia.
• Careful examination of the peripheral blood smear and bone marrow for
dysplastic (eg, hyposegmented neutrophils) or leukemic white blood cell
changes is diagnostic in MDS/AML, while the marrow in aplastic anemia
shows markedly reduced cellularity.

25. Megaloblastic
Erythropoeisis
Macroovalocytes.

26. •Pernicious Anemia:
• The presence of anti-intrinsic factor (IF) antibodies is
highly confirmatory for the diagnosis of pernicious anemia
(PA), with a sensitivity of 50 to 70 percent.
• Elevated serum gastrin levels, low pepsinogen I levels,
and a low ratio of pepsinogen I to pepsinogen II are highly
sensitive for the diagnosis of PA.

27. •B12 levels:
• >300 pg/mL (>221 pmol/L) – Normal result.
• 200 to 300 pg/mL (148 to 221 pmol/L) – Borderline result;
deficiency possible
• <200 pg/mL (<148 pmol/L) – Low; consistent with
deficiency (specificity of 95 to 100 percent)

28. •Metabolite Testing:
• Methylmalonic acid – 70 to 270 nanomol/L ̶ Normal.
• Homocysteine – 5 to 15 micromol/L ̶ Normal.
• Only homocysteine is elevated in folate deficiency.
• Both metabolite levels are elevated in B12 deficiency.
• Serum holotranscobalamin levels less than 35pmol/L ̶ In B12
deficiency.
• In future new serum cobalamin assay kits such as
holotranscobalamin may replace older kits and becomes standard
for testing of cobalamin deficiency.

29. TREATMENT
•PERNICIOUS ANEMIA:
• ROUTE: Intramuscular or Deep Subcutaneous.
• DOSAGE 1000 mcg (1 mg)/day for one week.
Followed by 1 mg/week for four weeks.
• If the underlying disorder persists 1 mg every month to be
given.(eg, surgical removal of terminal ileum).

30. •ORAL:
• DOSAGE 1000 to 2000 mcg/day.
• Given in patients with impaired intrinsic factor function.
• Does not require intrinsic factor or a functioning terminal
ileum.
• In the few randomized clinical trials which have been
reported, the use of oral B12 (1000 to 2000 mcg/day) in
newly diagnosed patients was found to be as effective as
intramuscular administration in obtaining short-term
hematological and neurological responses in vitamin B12-
deficient patients

31. •OTHER ROUTES:
• ROUTE:
• Sublingual.
• Nasal spray.
• Gel.
• These routes of treatment have not been adequately
studied and the available formulations are expensive.

32. •PARENTERAL:
• Pernicious anemia (PA) is typically treated.
• ROUTE: Intramuscular or deep subcutaneous.
• DOSAGE: 1000 mcg (1 mg) every day for one week.
Followed by 1 mg every week for four weeks.
• Parenteral B12 is inexpensive, relatively nontoxic, and
amounts given in excess of need are excreted harmlessly
in the urine.

33. PREVENTIVE MEASURES.
• VEGETARIANS:
• On Mediterranean diets (eg, fresh fruits and vegetables with little
in the way of animal-source foods) are at risk of development
of B12 deficiency and require vitamin B12 supplementation.
• PREGNANT WOMEN &BREAST-FEEDING MOTHERS:
• Need supplementation, as infants are also at much greater risk of
vitamin B12 deficiency than their mothers.
• GASTRIC SURGERY:
• Large doses of oral vitamin B12.