Pernicious anemia is the major form of vitamin B12 deficiency. It is caused by serum antibodies against intrinsic factor which leads to B12 deficiency rather than by B12 deficiency itself. Absorption of vitamin B12 requires intrinsic factor which is secreted by parietal cells. Pernicious anemia is marked by autoimmune attack on gastric mucosa and a loss in parietal cells. Approximately 75% of the affected patients have type I antibody that blocks the binding on vitamin B12 to the intrinsic factor. These antibodies are found in plasma and gastric juice.
A large percent expresses Type II antibodies. Type II antibodies prevent the binding of intrinsic factor-Vitamin B12 complex to the ileal cell receptors. About 85% to 90% of patients have Type III antibodies. Type III antibodies recognize the alpha and beta subunits of the gastric proton pump which is found on parietal cells. 1 It is also thought that an auto reactive CD4+ T-cell response causes gastric mucosal injury and this results in the formation of autoantibodies which makes the injury worse.
Anemia develops when intrinsic factor falls below the threshold level and vitamin B12 stores are depleted. This theory is backed up by experiments in animal models. This type of anemia can also be caused by achlorhydria and loss of pepsin secretion which is more common in elderly individuals. 1 Pernicious anemia occurs in all racial group but is somewhat more prevalent in Scandinavian and Caucasian populations. It is usually a disease of older adults with the median age of diagnosis at 60 and the incidence in people younger than 30 is rare.
There might be genetic predisposition to pernicious anemia but no specific genetic pattern has been observed yet. 1 Some of the characteristics of pernicious anemia include atrophy of fundic glands, deficiency of parietal cells or achlorhydria, intestinalization, and shiny or glazed tongue known as strophic glossitis. Because the gastric atrophy and achlorhydria are a result of autoimmunity and not Vitamin B12 deficiency, oral supplements do not correct them. 75% of the affected individuals also have central nervous system lesions with demyelination of dorsal and lateral tracts.
These lesions may cause spastic paraparesis, sensory ataxia, and sever paresthesias in lower limbs. It is rare but not impossible to have lesions in peripheral nerves as well. 1 Studies have shown orthostatic hypertension resulting from the lesions caused by B12 deficiency. Electrophysiological studies suggest that in Vitamin B12 deficiency axonal degeneration is reported as the main lesion: motor nerve conduction velocities are minimally slowed and distal latencies are increased causing a sympathetic nerve response dysfunction. 2
Diagnosis of pernicious anemia includes megaloblastic anemia, leukopenia, low serum vitamin B12, and elevated homocysteine. People with pernicious anemia are at a higher risk of developing gastric carcinoma. They are also at a higher risk of developing atherosclerosis and thrombosis resulting from elevated homocysteine levels. 1 Clinical manifestation of pernicious anemia is usually involved in numerous CNS and peripheral nervous system abnormalities. Pernicious anemia is a common disorder in elderly outpatients and was found to be associated with orthostatic hypotension since early 1960.
Since NE is not released properly by postganglionic sympathetic neurons, it results in impaired vasoconstriction and reduced intrathoracic vascular volume which leads to orthostatic hypotension. In 1962, a case of orthostatic hypotension associated with pernicious anemia was reported and the patient completely recovered after 12 weeks of parenteral vitamin B12. “In 1981, White and colleagues reported the first case of neurogenic OH as initial symptom of vitamin B12 deficiency. ” 3 In a paper by White, Reik, and Cutlip they discussed a case of a 69 year old man who complained of light headedness on standing, cold feet, and tingling to feet.
He had distal symmetrical polyneuropathy. He was diagnosed of diabetes mellitus sex years ago. His skin was pale. His blood pressure while standing was 96/60- with pulse rate of 86 beats per minute. The hemoglobin was 10. 2 g/dL, hematocrit was 30%, platelet count was 214,000/cu mm, WBC count was 3,200/cu mm, and MCV of 120 cu ? m. Patient experienced syncope which was a result of his orthostatic hypertension which is believed to be because of the neuropathy. And neuropathy is caused by B12 deficiency which in his case was due to pernicious anemia.
Peripheral neuropathy is common in pernicious anemia. It is caused by axonal degeneration and segmental demyelination. Because the patient had diabetes mellitus, one could easily argue that his neuropathy was a result of that but upon treatment with vitamin B12 replacement, his neuropathy improved. But managing his diabetes did not produce similar results. 2 A lot of the symptoms experienced by the 69 year old patient are applicable to our case such as the low blood pressure while standing, the pale skin, and tingling sensation in the feet.
Also high MCV, low platelet count, low hematocrit, low hemoglobin, and low white blood cell count were seen in both the 69 year old patient and our case. They both had vitamin B12 deficiency that is caused by pernicious anemia in 75% of the cases. In our case, her B12 deficiency can either be a result of her vegan diet or pernicious anemia. And because her diet change is recent, it is highly unlikely to be the cause especially because our body has enough B12 stored to not result in a deficiency this early.