Pernicious anemia symptoms

The nutritional requirement for vitamin Bjg is low. Adult humans require only about 3 micrograms per day, an amount easily acquired with normal eating habits. However, because plants do not synthesize vitamin Bjg, pernicious anemia symptoms are sometimes observed in strict vegetarians. 

Cobalt is one of twenty-seven known elements essential to humans (28) (see Mineral NUTRIENTS). It is an integral part of the cyanocobalamin [68-19-9] molecule, ie, vitamin B 2> only documented biochemically active cobalt component in humans (29,30) (see Vitamins, VITAMIN Vitamin B 2 is not synthesized by animals or higher plants, rather the primary source is bacterial flora in the digestive system of sheep and cattle (8). Except for humans, nonmminants do not appear to requite cobalt. Humans have between 2 and 5 mg of vitamin B22, and deficiency results in the development of pernicious anemia. The wasting disease in sheep and cattle is known as bush sickness in New Zealand, salt sickness in Florida, pine sickness in Scotland, and coast disease in AustraUa. These are essentially the same symptomatically, and are caused by cobalt deficiency. Symptoms include initial lack of appetite followed by scaliness of skin, lack of coordination, loss of flesh, pale mucous membranes, and retarded growth. The total laboratory synthesis of vitamin B 2 was completed in 65—70 steps over a period of eleven years (31). The complex stmcture was reported by Dorothy Crowfoot-Hodgkin in 1961 (32) for which she was awarded a Nobel prize in 1964. 

Cyano- and hydroxocobalamin - both can be converted to the physiologically relevant coenzymes methyl- and 5 -deoxyadenosylcobalamin in the liver -are used for therapeutical applications. When pernicious anemia caused by chronic atrophic gastritis has been diagnosed, it is treated as follows During the first 7 days of treatment, 1000 pg of hydroxocobalamin/d are administered parenterally, usually intramuscularly. Then, the same dose is given once weekly for 4-6 weeks. The aim is to alleviate the deficiency symptoms and at the same time to replenish the stores. Afterwards, 1000 pg hydroxocobalamin should be given parenterally every 2 months lifelong to avoid relapse [1, 2]. 

The chemistry, metabolism, and clinical importance of folic acid have been the subject of many excellent reviews (A7, Gil, H14, H20, Rl). Folic acid deficiency leads to a macrocytic anemia and leucopenia. These symptoms are due to inadequate synthesis of nucleic acid. The synthesis of purine bases and of thymine, required for nucleic acid synthesis, is impaired in folic acid deficiency. Detection of folic acid activity in biologic fluids and tissues is of the utmost importance it distinguishes between the various anemias, e.g., those due to vitamin Bi2 or folic acid deficiency. Because morphology of the abnormal red cell does not help in diagnosing vitamin deficiency, one must rely on assay methods for differential diagnosis. Treatment of pernicious anemia with folic acid has led to subacute combined degeneration of the spinal cord despite... 

Severe cyanocobalamin (vitamin B12) deficiency results in pernicious anemia that is characterized by megaloblastic anemia and neuropathies. The symptoms of this deficiency can be masked by high intake of folate. Vitamin B12 is recycled by an effective enterohep-atic circulation and thus has a very long half-hfe. Absorption of vitamin B12 from the gastrointestinal tract requires the presence of gastric intrinsic factor. This factor binds to the vitamin, forming a complex that... 

Folic acid supplements are given to pregnant women to decrease the risk of neural tube defects such as spina bifida. Prenatal vitamin preparations that contain higher concentrations of folic acid must be dispensed under a health care worker s guidance because high folate intakes can mask the symptoms of pernicious anemia. 

Which vitamin can mask the symptoms of pernicious anemia by alleviating the anemia but not preventing the neurological damage ... 

This vitamin is not made by plants or animals and can be synthesized only by a few species of microorganisms. It is required by healthy people in only minute amounts, about 3 p.g day. The severe disease pernicious anemia results from failure to absorb vitamin B12 efficiently from the intestine, where it is synthesized by intestinal bacteria or obtained from digestion of meat. Individuals with this disease do not produce sufficient amounts of intrinsic factor, a glycoprotein essential to vitamin B12 absorption. The pathology in pernicious anemia includes reduced production of erythrocytes, reduced levels of hemoglobin, and severe, progressive impairment of the central nervous system Administration of large doses of vitamin B12 alleviates these symptoms in at least some cases. ... 

Pernicious anemia Dementia Spinal degeneration Megaloblastic anemia Neuropsychiatric symptoms None Pernicious anemia is treated with IM or high-dose oral vitamin B12... 

The story of vitamin B12 began with pernicious anemia, a disease that usually affects only persons of age 60 or more but which occasionally strikes children.3 Before 1926 the disease was incurable and usually fatal. Abnormally large, immature, and fragile red blood cells are produced but the total number of erythrocytes is much reduced from 4-6 x 106 mm-3 to 1- 3 x 106 mm-3. Within the bone marrow mitosis appears to be blocked and DNA synthesis is suppressed. The disease also affects other rapidly growing tissues such as the gastric mucous membranes (which stop secreting HC1) and nervous tissues. Demyelination of the central nervous system with loss of muscular coordination (ataxia) and psychotic symptoms is often observed. 

Intramuscular injection of as little as 3-6 pg of crystalline vitamin B12 is sufficient to bring about a remission of pernicious anemia and 1 pg daily provides a suitable maintenance dose (often administered as hydroxocobalamin injected once every 2 weeks). For a normal person a dietary intake of 2-5 pg / day is adequate. There is rarely any difficulty in meeting this requirement from ordinary diets. Vitamin B12 has the distinction of being synthesized only by bacteria, and plants apparently contain none. Consequently, strict vegetarians sometimes have symptoms of vitamin B12 deficiency. 

Gastrointestinal signs and symptoms of vitamin B12 deficiency occur in 26% of cases. These include sore tongue, stomatitis, mucosal ulceration, appetite loss, flatulence, and constipation or diarrhea. Appetite loss, excess gas, and diarrhea are probably related to the underlying gastric disorder (i.e., gastric atrophy) in pernicious anemia. Gastrointestinal symptoms may occur in the absence of symptomatic anemia or macrocytosis. 

Symptoms of dehciency may include pernicious anemia, nerve problems and weakness, smooth or sore tongue. 

This clinical case involves cognitive impairment and mood changes due to vitamin Bj deficiency, sometimes called pernicious anemia. This is one of many illnesses that must be considered and tested for when a patient presents with cognitive symptoms. Other causes of cognitive impairment that are treatable are found in Table 6.2. It is critical that patients be examined and tested for these conditions as soon as symptoms are identified since the passage of time may lessen the probability of cure or improvement in function. 

Oral vitamin Bj2 supplementation appears to be as effective as parenteral, even in patients with pernicious anemia, because the alternate vitamin Bj2 absorption pathway is independent of intrinsic factor. Oral cobalamin is initiated at 1 to 2 mg daily for 1 to 2 weeks, followed by 1 mg daUy. Parenteral therapy is more rapid acting than oral therapy and should be used if neurologic symptoms are present. A popular regimen is cyanocobalamin 1,000 meg daily for 1 week, then weekly for 1 month, and then monthly. When symptoms resolve, daily oral administration can be initiated. 

Concerning possible masking of vitamin B12 deficiency by folic acid, blood counts in 11-33% of the patients with neurological symptoms of vitamin B12 deficiency are in the reference range. That means that in patients with severe funicular myelosis, a vitamin B12 deficiency psychosis, changes in the blood count may not occur, while on the other hand in patients with severe pernicious anemia neurological symptoms are not inevitably present. 

A. Pernicious anemia occurs when the stomach does not produce adequate intrinsic factor for absorption of vitamin B12, which is required for the conversion of methylmalonyl CoA to succinyl CoA and homocysteine to methionine. A vitamin B12 deficiency results in the excretion of methylmalonic acid and an increased dietary requirement for methionine. The methyl group transferred from vitamin B12 to homocysteine to form methionine comes from 5 -methyl tetrahydrofolate, which accumulates in a vitamin B12 deficiency, causing a decrease in folate levels and symptoms of folate deficiency, including increased levels of FIGLU and decreased purine biosynthesis. 

Chronic large doses may interfere with sleep patterns and cause malaise, irritability, and gastrointestinal symptoms such as anorexia, nausea, bloating, flatulence, and bad taste. Seizure threshold may be lowered in epileptics and progression of neurologic injury in pernicious anemia has also been reported. 

Vitamin Bn can be deficient due to a lack of intrinsic factor, which is a glycoprotein secreted by gastric parietal cells. A lack of intrinsic factor or a dietary deficiency of cobalamin can cause pernicious anemia and neuropsychiatric symptoms. The only known treatment lor intrinsic factor deficiency (vitamin Bn deficiency) is intramuscular injection of cyanocobalamin throughout the patient s life. 

Vitamin B12 deficiency, a macrocytic anemia, can be due to inadequate intake, decreased absorption, or inadequate utilization. Anemia caused by a lack of intrinsic factor, resulting in decreased vitamin B12 absorption, is called pernicious anemia. Vitamin B12 levels and the reticulocyte count are usually low. Neurologic symptoms are often present. Oral or parenteral therapy may be used for replacement therapy. 

It is of paramount importance to rule out vitamin B12 deficiency when folate deficiency is detected, as symptoms are similar. Laboratory changes associated with folate deficiency are similar to those seen in vitamin Bn deficiency, except vitamin Bn levels are normal. Decreases occur in the serum folate level (<3 ng/mL) within a few days of dietary folate limitations. The RBC folate level (<150 ng/mL) also declines and may be a better indicator of deficiency, as levels remain constant throughout the life span of the erythrocyte. Serum folate levels are sensitive to short-term changes such as dietary restrictions or alcohol intake, which may result in a short-term decline in serum levels with adequate tissue stores. It should be noted that an estimated 60% of patients with pernicious anemia have falsely low RBC folate levels, in all probability due to the requirement of cobal-amin for the normal transfer of methyltetrahydrofolate from plasma to cells. Additionally, if serum or erythrocyte folate levels are borderline, serum homocysteine is usually increased with a folic acid deficiency. If serum MMA levels are also elevated, vitamin B12 deficiency needs to be ruled out. 

E. The correct diagnosis is thalassemia minor because the patient had been asymptomatic until age 7 years. If he had thalassemia major or Cooley anemia, he would have exhibited symptoms as early as his first birthday. Pernicious anemia leads to a macrocytic or megaloblastic anemia, whereas aplastic anemia is characterized by normal sized erythrocytes. 

Which one of the following will reverse symptoms of megaloblastic anemia in pernicious anemia but has minimal impact on the neurologic dysfunction ... 

Answer A. Folic acid can relieve hematologic symptoms in vitamin B12 deficiency because it can serve as a cofactor for methionine synthetase in the conversion of homocysteine to methionine. However, it cannot replace vitamin Bu (cyanocobalamin) in the reaction that converts malonyl-CoA to succinyl-CoA, so folic acid has no impact on the neurologic dysfunction of pernicious anemia. 

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