Vitamin b12 deficiency anemia

Anemia caused by vitamin B¹² deficiency anemia is blood disorder, which characterized by abnormalities in the DNA synthesis of the blast cells due to the deficiency of vitamin B¹² and/or folic acid.

The vitamin B¹² molecule consists of the nucleotide 5,6-dimethylbenzimidazole linked at right angles to a four-pyrrole ring with a cobalt atom (the corrin nucleus). Several cobalamins (vitamin B¹² compounds), which vary only in the ligand attached to the cobalt atom, occur in nature.

Methylcobalamin (MeCbl) and adeno-sylcobalamin (AdoCbl), physiologic cobalamin coenzymes, perform the biochemical roles of B¹². MeCbl functions in nucleic acid metabolism and is the cofactor involved in defective DNA synthesis. AdoCbl serves as a scavenger system for catabolism of aliphatic amino acids, lipid membranes, and precursors of propionate; it may be the cofactor involved in altered myelin synthesis and repair.

Vitamin B¹² is available in meat and animal protein foods. Its absorption is complex; it occurs in the terminal ileum and requires intrinsic factor, a secretion of parietal cells of the gastric mucosa, for transport across the intestinal mucosa. Vitamin B¹² in food binds to binding proteins (R binders) in saliva that protect B¹² in the acid milieu of the stomach. When this B¹² complex (B¹²-R binders) enters the small intestine, pancreatic enzymes cleave it, and the vitamin B¹² binds to the intrinsic factor.

Etiology of vitamin B¹²-deficiency anemia

1. Reduced intake: nutritional deficiency.

2. Strict veganism.

3. Impaired absorption:

• gastric cause: total or partial gastrectomy;

• intestinal cause: chronic tropical sprue, intestinal stagnant loop syndrome (e.g. jejunal diverticulosis, blind loop, strictures), scleroderma, Crohn's disease and ileal resection, congenital selective malabsorption with proteinuria, Zollinger Ellison syndrome, severe pancreatitis, coeliac disease;

• hemodialysis;

• transport protein defects: hereditary lack of transcobalamin II, abnormal transcobalamin II, abnormal B¹² binding protein.

4. Competition for cobalamin:

• bacterial colonization of the small intenstine;

• fish tapeworm infection;

• bacteria "blind loop" syndrome.

5. Impaired metabolism:

• inhibitors of dihydrofolate reductase;

• purine antagonists;

• pyrimidine antagonists;

• alcohol.

Pathogenesis: Methylcolabamin is an essential cofactor in the conversion folic acid to its active form. When this reaction is impaired folate metabolism is deranged and occurs defects in DNA synthesis with megaloblastic maturation patterns in patients who are deficient to cobalamin.

The lack of vitamin В¹² lead to the biochemical disorder such as conversion of homocysteine to methionine which takes part in production of phospholipids required for myelin formation. This biochemical abnormality may contribute to the neurological complication of cobalamine deficiency.

The jaundice may be explained by the excess breakdown of hemoglobin from immature crythroid bone marrow which easily damaged than normal erythrocytes and hence have a shortened life span.

Clinical features

There are three clinical syndromes: anemic, affection of the digestive system and neurological syndrome.

Anemic syndrome includes such complaints: fatigue, tiredness, palpitation, dyspnea, giddiness. The skin is pallor with lemon yellow tint, slightly icteric skin and sclerae, swallowing face, slight pedal edema. Physical examination of the cardiovascular system reveals tachycardia, systolic murmur at the apex and pulmonary artery, systolic bruits over carotid arteries, ischemic changes on ECG, heart failure. The symptoms and signs of gastrointestinal affection: anorexia, Hunter's glossitis (sore, smooth red tongue, with ulcer over the edge), atrophic gastritis, bladder and bowel dysfunction, diarrhea, enlarged liver and sometimes spleen.

Neurological syndrome includes peripheral neuropathy and combined degeneration of the spinal cord where the posterior and lateral columns undergo demyelization. The symptoms and signs are next: numbness, tingling, paresthesia in the extremities, difficulty in walking, ataxia, position and vibration senses are diminished, dumbness. There may be sphincter disturbance. Reflexes may be diminished or increased. The Romberg and Babinski signs may be positive. Affections of the mental state reflect irritability, diminished memory, even severe dementia or psychosis. In young females there may be infertility.

Additional methods of examination

Clinical blood analysis:

- hemoglobin concentration decreased moderately; red blood cell count decreased pronouncly;

- mean cell volume ranging from 100 to 140 fl;

• color index > 1,2;

• moderate leucopenia;

• mild, usually asymptomatic thrombocytopenia;

• anisocytosis - macrocytosis;

• poikilocytosis - ovalocytosis;

• hyperchromia, ring or pessary cells;

• red blood cells may show: Howel-Jolly bodies, Cabot rings;

• hypersegmentes neutrophils;

• macropolycytes (large neutrophils).

Bone marrow:

• hyperplasia of erythroid elements;

• megaloblasts - gigantic cells with large nucleus oval shape and basophilic cytoplasm;

• gigantic metamyelocytes;

• megakaryocytes.

Biochemical blood analysis:

• increased level of unconjugated bilirubin;

• increased level faeces stercobilin;

• increased level of lactatdehydrogenasa.

Special tests for diagnosing vitamin В¹² deficiency:

• low serum vitamin B¹² assay;

• increased urinary excretion of methylmalonic acid;

• low radioactive vitamin B¹² absorption test (Schilling's test);

• reticulocyte response to vitamin B¹² administration.