Physiology of Vit B12
Source: in animal sources only, not in plants
Requirements: 1 ug/day
Absorption: Vit B12 binds to intrinsic factor produced by the parietal cells in the
stomach to be absorbed in the terminal part of ileum where it binds to a specific
receptor
Transport: in the plasma bound to transcotalamine-II
Stores: in the liver sufficient for 2-3 years of normal consumption
Function:
• Synthesis of DNA in dividing cells
• Myelination of nerve fibers
Etiology
1. Diminished intake:
a. Dysphagia, starvation
b. Vegetarians
2. Diminished absorption:
a. Gastrectomy, gastritis, gastric carcinoma
b. Addissonian pernicious anemia:
autoimmune disease, which affects north Europe, females> males, rare below
age 30 years, The disease is genetic (associated with HLA – A3 & B7).
with 3 types of antibodies:
Anti-parietal cells antibodies
Blocking antibodies: that prevents binding of Vit B 12 to intrinsic factor
Binding antibodies: that prevents binding of intrinsic factor-Vit B12 complex to
terminal ileum receptors
It may be associated with other autoimmune disorders e.g. thyroiditis, vitiligo.
c. Ileal disease:
Regional ileitis, T.B
Diphylopotharium latum
Blind loop syndrome
Malabsorption syndrome
3. Increase requirements: Pregnancy, malignancy
4. Reduced storage: Liver cirrhosis (uncommon)
5. Others: Lack of transcobalamin II (congenital).
Pathogenesis
• In dividing cells there’s duplication of DNA & cytoplasm expansion (RNA).
• In case of Vit B12 deficiency, imbalance exists between DNA synthesis (depends on B12)and
cytoplasm (RNA is not affected) delay in cell division formation of megaloblasts.
1. B.M.
• Some megalobasts are destroyed in bone marrow (ineffective enythropoiesis):
1- Destruction of RBCs:↑ LDH,↑ serum iron &↑ hemosiderin in BM.
2- Destruction of platelets thrombocytopenia.
3- Destruction of WBCs:↑ serum muramidase.
2. Peripheral blood:
Released cells are at variable stage of development & undergo further destruction in RES
pancytopenia:
1) RBCs: anisocytosis, poikilocytosis, cabot ring
• & Howel-Jolly bodies
(nuclear remmants).
2) Platelets: More thrombocytopenia.
3) WBCs: Leucopenia with multi segmented PMNLs.
3. GIT: Atrophy of epithelial cells occurs due to rapid turn over of these cells.
4. CNS: Defective myelination of nerve fibers impaired nerve conduction.
Clinical Picture
1. C/P of anemia in general (FOG P
2. C/P specific for Vit B12 deficiency:
• Blood:
Bleeding tendency (↓ platelets
↑ Liability for infection (↓ WBCs).
• GIT:
Tongue: Red glazed.
Stomach: Dyspepsia, nusea, vomiting.
Intestine: Diarrhea.
Hepatosplenomegaly.
• CNS: Subacute combined degeneration (SCD) look neurology.
3. C/P of cause: e.g.
In addission’s aneamia (preniciouse anemia)
Usually blue eyed Northen Europeans.
Other autoimmune disease e.g. addision, vitiligo, Grave’s disease.
There’s increased incidence of gastric carcinoma.
Investigations
I.↓ Hb,↓ PCV,↓ RBCs,↑ ESR.
II. Type of anemia: Megaloblastic normochromic:
• ↑ MCV( > 115 FL).
• Normal MCHC.
III. The cause:
Pancytopenia
1. RBCs: Howel-Jolly bodies, cabbot rings, anisocytosis & poikilocytosis +↑ Bilirubin
+↑ serum iron +↑ serum LDH +↑ hemosiderin deposition in BM.
2. Platelets: Thrombocytopenia +↑ bleeding time.
3. WBCs: Leucopenia +↑ segmented cells +↑ muramidase.
4. BM:
• ↑ Megaloblast precursors.
• ↓ Reticulocytes (characterstic).
↓ Vit B12
1. Low serum Vit B12 (200 – 800 Pg/ml).
2. IM Vit B12 Reticulocytosis (therapeutic test).
VI. Investigation of Etiology: e.g.
• Preniciouse aneamia:
Detection of antibodies.
Gastric function test for achlorhydria.
Endoscopy to exclude gastric carcinoma.
• Investigations for malabsorption syndrome.
• Chilling test:
Procedure: 1000 ug B12 IM Then 1 Ug oral radioactive B12.
Normally: 25% of radioactive Vit B12 appears in urine / 24 hrs (store is already
saturated by IM Vit B12).
Abnormal response: < 5% of radioactive B12 / 24 hr urine Malabsorption.
- Correction by giving intrinsic factor prenicious anemia.
- Correction by antibiotic course bacterial over growth.
Treatment
I. Replacement therapy: B12 (Hydroxy cobalamine) 100 Ug IM daily till RBCs count to 5 million
/mm3 one ampoule IM/ month for life in cases of malabsorption.
II. Treatment of cause: e.g. HCL + pepsin during meals in preniciouse anemia.
III. Blood transfusion if:
* HB < 7 gm%.
* HF or ischemic heart disease.
