Symptoms of vitamin B12 insufficiency
Reasons for Low Vitamin B12
Reduced Consumption
Animal products are the primary source of vitamin B12, also known as cyanocobalamin. Vitamin B12 is scarce in fruits and vegetables. A strict vegetarian diet devoid of meat, eggs, and milk puts them at risk of developing a vitamin B12 deficiency. Due to sufficient vitamin reserves, an inadequate diet can develop anemia years later.
Reduced Absorption
Any one of the processes involved in the absorption of vitamin B12 can be disrupted, which can lead to an impairment in its absorption.
Gastric factors:
• Loss of pepsin secretion and achlorhydria (deficiency of stomach acid): Pepsin and the low pH that HCl produces are necessary for the release of vitamin B12 from bound proteins in meals.
gastrointestinal elements
• Loss of absorptive surface: Ileal resection, diffuse ileal disease, and Crohn's disease cause the intrinsic factor-vitamin B12 combination to be absorbed improperly. Both nontropical and tropical sprue can cause vitamin malabsorption.
• Competition from parasites or bacteria for vitamin B12.
- Bacterial competition: Diverticulosis or blind loop, stenotic regions caused by abnormal gut structure or surgical aftereffects. Under these circumstances, intestinal stasis leads to bacterial overgrowth that competes with the body for vitamin B12.
- Competition between parasites: Fish tapeworm An infestation of Diphyllobothrium latum can cause a deficit by posing a competition for vitamin B12.
harm to the pancreas' exocrine gland
Vitamin B12 cannot be liberated from R-binder vitamin B12 complexes when exocrine pancreatic activity is lost.
A Rise in Demand
Even with normal absorption, the requirement for vitamin B12 might be so high as to result in a relative deficit. Conditions such as pregnancy, hyperthyroidism, disseminated malignancy, and persistent infections can all cause this.
Definition of Pernicious Anemia
Chronic pernicious anemia (PA) is caused by a lack of intrinsic factor, which impairs vitamin B12 absorption and ultimately results in megaloblastic anemia.
Rate of occurrence
Though it is extremely uncommon in India, pernicious anemia can affect people of any race. Due to the inclination to develop antibodies against certain self-antigens, a genetic predisposition is believed to exist.
Age
A illness of advanced age, pernicious anemia typically manifests in the fifth or eighth decades of life.
Sexual
Compared to men, women are more involved (F:M equals 1.5: 1).
Pathogenesis etiology
A type of autoimmune disease called pernicious anemia arises when the stomach mucosa is destroyed. Evidence supporting an autoimmune etiology includes:
• There is strong evidence linking it to other autoimmune conditions such as Graves disease, Hashimoto thyroiditis, and adrenalitis.
• Damage to the stomach's parietal cells under a microscope is followed by a dense infiltration of lymphocytes and plasma cells. This leads to chronic atrophic gastritis and is mediated by humoral and cellular immune responses.
• Reaction to steroid use.
• The majority of patients have autoantibodies. There are two main categories of autoantibodies.
- Antibody against intrinsic factor (IF)
◆ Type I (blocking) antibody: Found in 50–75% of patients, this antibody prevents vitamin B12 from binding to IF. It is present in gastric juice and plasma.
◆ Antibody type II (binding): It binds to the IF-vitamin B12 complex and stops it from connecting to ileal receptors. Roughly 40% of patients have it.
- Type III parietal cell antibody: It is not unique to PA or other autoimmune diseases; rather, it targets the ATPase pump in parietal cells. It is seen in elderly patients with chronic nonspecific gastritis as well as 90% of PA patients.
The activation of CD4+ T cells, which starts the autoimmune process (Fig. 4.9), causes damage to the stomach. Autoantibodies are secondary to mucosal injury, and they worsen the damage to parietal cells that secrete IF. When enough parietal cells are destroyed, leading to an IF shortage, and when vitamin B12 stores are depleted, anemia ensues. Therefore, although they are useful for diagnosis, autoantibodies are not the main cause of chronic atrophic gastritis.
Features of the Clinic
• Onset: Stealthily develops over time unless therapy is applied to stop it.
• The traditional presenting triad of paraesthesias, sore throat, and weakness.
• Tongue: A painful red, "beefy" tongue caused by papillae atrophy and glossitis. The patient reports feeling less hungry and with less taste.
• Peripheral neuropathy: dispersion of paresthesia or numbness in the socks and gloves. This tingling is bilateral, symmetric, starts at the tips of the toes, moves proximally, and is intense.
• Ataxia: impaired vibration and position sense, disorganized gait, and lack of voluntary coordination of muscular movement.
Serum homocysteine elevation is associated with an increased risk of atherosclerosis and thrombosis.
Results of the Lab
Bone marrow and blood
The alterations seen in the blood and bone marrow are comparable to those previously mentioned for all forms of megaloblastic anemia.
morphology
An antagonistic system It is common to find abnormalities in the stomach and tongue.
• Atrophic glossitis: The tongue has a glazed, glossy, and meaty appearance.
• Stomach: Reduced secretion of pepsin, intrinsic factor, and hydrochloric acid is linked to diffuse chronic atrophic gastritis.
◆ The loss of both chief and parietal cells, along with the atrophy of the glands (mostly in the fundus), is the typical histological hallmark. Parietal cells totally vanish as the illness worsens.
There is a strong infiltration of lymphocytes and plasma cells. ◳ Mucosal cell nuclei are enlarged and resemble megaloblast nuclei. The severity of gastritis increases with age.
- Intestinal metaplasia: Mucus-secreting goblet cells that mimic those lining the large intestine replace the epithelium lining the glands. This kind of metaplasia is referred to as intestinalization or intestinal metaplasia.
Rather than a vitamin B12 shortage, the immunological response is to blame for the metaplastic alterations and stomach atrophy.
75% of instances of severe pernicious anemia have abnormalities in the central nervous system.
• Demyelination in the dorsal and lateral tracts: The dorsal and lateral tracts of the spinal cord exhibit demyelination. Dorsal tract demyelination results in sensory ataxia, while lateral tract demyelination induces spastic paraparesis and acute paresthesia in the lower limbs. These neurologic abnormalities associated with vitamin B12 deficiency are referred to as "subacute combined degeneration" because both sensory and motor pathways are affected.
Biochemical Characteristics
• Tests for vitamin B12 insufficiency diagnosis:
- Lower serum vitamin B12 levels
Elevation of serum methylmalonic acid
Methylmalonic acid excretion in the urine: elevated.
• Schilling test for absorption of vitamin B12
Use: The Schilling test is useful in differentiating pernicious anemia, or megaloblastic anemia caused by intrinsic factor (IF) deficiency, from other types of vitamin B12 insufficiency. While it is still a diagnostic test for PA, it is currently extremely rarely used.
Approach and interpretation: A patient who is fasting is given 1 µg of radioactive vitamin B12.
After that, 1,000 µg of non-radioactive vitamin B12 are injected intramuscularly. The injected vitamin B12 flushes out the ingested radioactive vitamin B12, which will be eliminated through urine, and saturates vitamin B12 binding proteins. Urine is gathered for a full day.
Stage 2: The test is repeated with the addition of oral intrinsic factor to radioactive vitamin B12 if the results are abnormal.
If the excretion of urine returns to normal, the diagnosis of intrinsic factor insufficiency can be attributed to either gastrectomy or pernicious anemia.
Stage 3: If the excretion remains aberrant, either the lesion is located in the terminal ileum or there could be an overgrowth of bacteria. A seven-day regimen of oral tetracycline and antibiotics may be used to treat the bacterial overgrowth. Following an oral tetracycline regimen, the test is redone. In a similar vein, administering pancreatic enzyme extracts together with oral vitamin B12 should direct pancreatic dysfunction if excretion returns to normal, indicating malabsorption of vitamin B12 caused by bacterial overgrowth in the intestine.
• Particular diagnostic procedures for pernicious anemia include: - Serum anti-intrinsic factor antibodies, or antibodies to intrinsic factor, which are very specific for the disease. Rather of determining whether cobalamin deficiency is present or absent, their presence establishes the cause of vitamin B12 deficiency. Anti-intrinsic antibodies are more specific than anti-parietal cell antibodies in 85–90% of cases.
- Achlorhydria induced by pentagastrin/histamine.
Extremely low intrinsic factor levels.
• Additional non-specific testing
- Pepsinogen I dropped - Serum gastrin increased
A stomach biopsy reveals mucosal atrophy as well as an inflammatory lymphocyte and plasma cell infiltration.
FOLATE DEFICIENCY ANEMIA
Megaloblastic anemia, which is comparable to vitamin B12 insufficiency, is caused by folic acid deficiency.
That being said, there are no neurologic abnormalities associated with vitamin B12 insufficiency.
Reasons for Insufficient Folic Acid
The body has limited stores of folate, and months of negative balance can cause a deficit. lists the main causes of folic acid deficiency. Clinical Features
Similar to anemia caused by a vitamin B12 deficiency, minus the neurological symptoms.
Note: Folate therapy also helps with the hematologic signs of vitamin B12 deficient anemia. Nevertheless, folate does not stop the development of the neurological deficiencies caused by a vitamin B12 deficiency—in fact, it can make things worse. Always rule out vitamin deficiencies before starting folate therapy in megaloblastic anemias.
Results of the Lab
Peripheral Blood is Identical to those listed under megaloblastic anemia laboratory results Bone Marrow is Comparable to those listed under megaloblastic anemia laboratory results.
Biochemical Parameters Similar to those listed under "Lab results of megaloblastic anemia."
Particular Folic Acid Deficiency Tests
• Reduced serum folic acid levels.
• FIGLU in the urine: When histidine is converted to glutamate, formiminoglutamate is an intermediate product that is expelled in excess.
