Vitamin B deficiency anemia 12 , where pernicious anemia is a type, is a disease in which insufficient red blood cells are produced due to vitamin B deficiency < sub> 12 . The most common initial symptom is fatigue. Other symptoms may include shortness of breath, pale skin, chest pain, numbness in hands and feet, poor balance, smooth red tongue, poor reflexes, depression and confusion. Without treatment some of these problems can become permanent.
Although pernicious anemia technically refers to cases resulting from insufficient intrinsic factors, it is often used to describe all cases of anemia due to insufficient vitamin B 12 . The lack of intrinsic factor is most often due to autoimmune attacks on the cells that make it in the stomach. Can also occur after surgical removal of some of the stomach or from a congenital disorder. Other causes of low vitamin B 12 include insufficient dietary intake (such as the vegan diet), celiac disease, or tapeworm infection. When suspected, the diagnosis is made by blood and, occasionally, a bone marrow test. Blood tests may show less but more red blood cells, lower pink blood cell count, lower vitamin B 12 , and antibodies to intrinsic factors.
Pernicious anemia, due to a lack of intrinsic factors, can not be prevented. Vitamin B deficiency 12 because other causes can be prevented by a balanced diet or with supplements. Pernicious anemia can be easily treated with vitamin B sub-injection or vitamin 12 . If the symptoms are severe, an injection is usually recommended initially. For those who have difficulty swallowing pills, nasal sprays are available. Often, care is done for life.
Pernicious anemia due to autoimmune problems occurs in about one per 1000 people. Among those over the age of 60, about 2% have conditions. This more often affects people of northern European descent. Women are more often affected than men. With proper care, most people lead normal lives. Because the risk of stomach cancer is higher, those with pernicious anemia should be checked regularly for this. The first obvious explanation was by Thomas Addison in 1849. The term "evil" means "dangerously harmful"; the term was coined and right before the availability of effective treatment.
Video Vitamin B12 deficiency anemia
Signs and symptoms
The symptoms of pernicious anemia appear slowly. Untreated, it can lead to neurological complications, and in serious cases, death. Many signs and symptoms are due to anemia itself, when anemia is present. Symptoms may include tingling triads or other skin sensations (paresthesia), tongue pain (glossitis), and general fatigue and weakness. It presents with a number of more common symptoms, including depressed mood, mild fever, diarrhea, dyspepsia, weight loss, neuropathic pain, jaundice, angular cheilitis, pallid appearance and lips dehydrated or ruptured and dark circles around the eyes, as well as brittle nails, and thinning and graying of hair. Since PA may affect the nervous system, symptoms may also include difficulties in proprioception, memory changes, mild cognitive impairment (including difficulty concentrating and slow response, colloquially referred to as brain fog), and even psychosis, urinary disorders, loss of sensation in the legs, unstable gait, difficulty walking, muscle weakness and irregularities. Anemia can also cause tachycardia (rapid heartbeat), heart murmurs, pale yellow candles, changes in blood pressure (low or high), and shortness of breath (known as "sigh"). Shortages can also present with thyroid disorders. In severe cases, anemia can lead to evidence of congestive heart failure. Severe chronic PA complications are subacute spinal cord compound degeneration, leading to distal sensory loss (posterior columns), absence of ankle reflexes, increased knee reflex response, and plantar extensor responses. In addition to anemia, hematologic symptoms may include cytopenias, intramedullary haemolysis, and pseudothrombotic microangiopathy. Pernicious anemia may contribute to delays in physical growth in children, and may also be the cause of delayed puberty for teenagers.
Maps Vitamin B12 deficiency anemia
Cause
Vitamin B 12 can not be produced by the human body, and must be obtained from food. When foods containing B 12 are eaten, vitamins are usually bound to proteins and released by proteases released by the pancreas in the small intestine. After its release, most of the B 12 is absorbed by the body in the small intestine (ileum) after binding to a protein known as an intrinsic factor. The intrinsic factor generated by parietal cells of the gastric mucosa (gastric layer) and intrinsic complex factor-B 12 is absorbed by cubilin receptors in ileal epithelial cells. PA is characterized by a deficiency of B 12 caused by the absence of intrinsic factors.
PA can be regarded as the final stage of immune gastritis, a disease characterized by gastric atrophy and the presence of antibodies against parietal cells and intrinsic factors. A specific form of chronic gastritis, type A gastritis or atrophic gastritis of the body, strongly associated with PA. This autoimmune disorder is localized to the body of the stomach, where the parietal cells are located. Antibodies to intrinsic factors and parietal cells cause the destruction of oxyctic gastric mucosa, in which parietal cells are present, leading to the loss of intrinsic factor synthesis. Without intrinsic factor, ileum can no longer absorb B 12 .
Although the exact role of Helicobacter pylori infection in PA remains controversial, evidence suggests that H. pylori is involved in the pathogenesis of the disease. A long-standing H. pylori infection can cause gastric autoimmunity by a mechanism known as molecular mimicry. Antibodies produced by the immune system can become cross-reactive and can bind both H. pylori antigens and those found in the gastric mucosa. Antibodies are produced by active B cells that recognize pathogenic peptides and self-derived peptides. Autoantigen which is believed to cause autoreactivity is the alpha and beta subunits of H /K -ATPase.
Less commonly, H. pylori and Zollinger-Ellison syndrome can also cause nonautoimmune gastritis forms that can cause pernicious anemia.
Disorders B 12 may also occur after gastric removal (gastrectomy) or gastric bypass surgery. In this operation, either the abdomen producing gastric secretions will be removed or they are bypassed. This means intrinsic factors, as well as other factors required for absorption of B 12 , are not available. However, lack of B 12 after gastric surgery is usually not a clinical problem. This may be because the body stores B for years 12 in patients with adequate liver and stomach surgery equipped with vitamins.
Although no specific PA susceptibility gene has been identified, genetic factors are likely to be involved in the disease. Pernicious anemia is often found in conjunction with other autoimmune disorders, suggesting a common autoimmune susceptibility gene may be a contributing factor. Regardless, previous family studies and case reports focused on PA have suggested that there is a genetic predisposition of PA in particular, and close relatives of PA patients appear to have higher incidence of PA and associated PA conditions. Furthermore, it is further demonstrated that the formation of antibodies to gastric cells is an autosomal dominant gene determined, and the presence of antibodies against gastric cells may not always be associated with the occurrence of atrophic gastritis associated with PA.
Pathophysiology
Although a healthy body stores three to five years of B 12 in the liver, the normally undetectable autoimmune activity in a person's intestine over a long period of time leads to B 12 thinning and anemia generated. B 12 is required by the enzyme for two reactions: conversion of methylmalonyl CoA to succinyl CoA, and conversion of homocysteine ​​to methionine. In the latter reaction, methyl groups of 5-methyltetrahydrofolate were transferred to homocysteine ​​to produce tetrahydrofolate and methionine. This reaction is catalyzed by a methionine synthase enzyme with B 12 as the essential cofactor. During deficiency B 12 , this reaction can not proceed, leading to the accumulation of 5-methyltetrahydrofolate. This accumulation depletes the other folate types necessary for the synthesis of purines and thymidylates, which are necessary for DNA synthesis. Inhibition of DNA replication in red blood cells results in the formation of large and fragile megaloblastic erythrocytes. The neurological aspect of the disease is thought to arise from the accumulation of methylmalonyl CoA due to the need for B 12 as a cofactor against the methylmalonyl CoA mutase enzyme.
Diagnosis
PA can be suspected when the patient's blood smear shows a large, fragile, immature erythrocytes, known as megaloblasts. The first diagnosis of PA requires demonstration of megaloblastic anemia by performing a complete blood count and blood smear, evaluating the average corpuscular volume (MCV), as well as the concentration of corpuscular hemoglobin (MCHC). PA is identified with high MCV (macrocytic anemia) and normal MCHC (normochromic anemia). Ovalocytes are also usually seen in blood smears, and the pathognomonic features of megaloblastic anemias (which include PA and others) are hypersegmented neutrophils.
Vitamin B serum levels 12 are used to detect the deficiency, but they do not distinguish the cause. Levels of vitamin B 12 can be very high or low and data for sensitivity and specificity vary greatly. Normal serum levels can be found in cases of deficiency in which myeloproliferative disorders, liver disease, transcobalamin II deficiency, or overgrowth of intestinal bacteria occur. Low levels of vitamin B serum 12 may be caused by factors other than B 12 deficiency, such as folate deficiency, pregnancy, oral contraceptive use, haptocorrine deficiency, and myeloma.
The presence of antibodies to gastric parietal cells and intrinsic factors are common in PA. Parietal cell antibodies are found in other autoimmune disorders and also in up to 10% of healthy individuals, making the tests non-specific. However, about 85% of PA patients have parietal cell antibodies, which means they are sensitive markers for this disease. Intrinsic factor antibodies are much less sensitive than parietal cell antibodies, but they are much more specific. They are found in about half of PA patients and are very rare in other disorders. This antibody test can differentiate between PA malabsorption and food-B 12 . The combination of both intrinsic factor antibody tests and parietal cell antibodies can improve the sensitivity and overall specificity of the diagnostic outcome.
Certain metabolite accumulation occurs in B 12 deficiency because of its role in cellular physiology. Methylmalonic acid (MMA) can be measured in both blood and urine, whereas homocysteine ​​is measured only in blood. An increase in both MMA and homocysteine ​​can differentiate between B 12 and folate deficiency because only homocysteine ​​increases in the latter.
Increased gastrin levels can be found in approximately 80-90% of cases of PA, but can also be found in other gastritis forms. Decreased levels of pepsinogen I or decreased pepsinogen I for pepsinogen II ratios can also be found, although these findings are less specific for PA and can be found in food malabsorption-B 12 and other gastritis forms.
The diagnosis of type A atrophic gastritis should be confirmed by gastroscopy and a gradual biopsy. About 90% of individuals with PA have antibodies to parietal cells; However, only 50% of all individuals in the general population with these antibodies have pernicious anemia.
The form of vitamin B 12 deficiency other than PA should be considered in the differential diagnosis of megaloblastic anemia. For example, the state of B 12 -defficiency that causes megaloblastic and possibly erroneous anemia for classical PA may be due to infection with tapeworm Diphyllobothrium latum , probably because of parasite's competition with host for vitamin B 12 .
The classic test for PA, Schilling test, is no longer widely used, as more efficient methods are available. This historic test consists, in the first step, taking oral doses of vitamin B 12 , followed by quantitation of vitamin in the urine of the patient for 24 hours through radioactivity measurements. The second step of the test repeats the first step regimen and procedure, with the addition of oral intrinsic factor. A patient with PA presents a number of intrinsic factors lower than the normal amount; therefore, the addition of intrinsic factor in the second step results in an increase in vitamin B absorption 12 (above the baseline set at the first). Schilling tests differentiate PA from other forms of B 12 deficiency, in particular, from Imerslund-Grasbeck Syndrome (IGS), vitamin B12 deficiency caused by mutations in cobalamin receptors.
Treatment
PA care varies by country and region. Opinions vary on administrative efficacy (parenteral/oral), number and time interval of dose, or vitamin B 12 form (eg cyanocobalamin/hydroxocobalamin). A more comprehensive study is still needed to validate the feasibility of certain therapeutic methods for PA in clinical practice. The permanent cure for PA is lacking, although the filling of B 12 should be expected to result in cessation of symptoms associated with anemia, cessation of neurological damage, and in cases where neurological problems are not advanced, neurological recovery and complete and permanent remission of all symptoms, for B 12 added. Repetition B 12 can be completed in various ways.
Intramuscular injection
Standard treatment for PA is intramuscular injection of cobalamin in the form of cyanocobalamin (CN-Cbl), hydroxocobalamin (OH-Cbl) or methylcobalamin.
Oral dose
Treatment with high doses of vitamin B 12 by mouth also appears to be effective.
Prognosis
Someone with a well-cared for PA can live a healthy life. Failure to diagnose and treat in time, however, can result in permanent neurological damage, excessive fatigue, depression, memory loss, and other complications. In severe cases, neurologic complications of pernicious anemia can lead to death - hence the name, "destructive", meaning lethal.
A relationship has been observed between pernicious anemia and some types of gastric cancer, but causal relationships have not been established.
Epidemiology
PA is estimated to affect 0.1% of the general population and 1.9% of those over the age of 60, accounting for 20-50% of B 12 deficiency in adults. The literature review shows that the prevalence of PA is higher in Northern Europe, especially in Scandinavian countries, and among people of African descent, and that increased awareness of disease and better diagnostic tools may play a role in apparently higher incidence rates.
History
The phenomenon was first described in 1822 by Dr James Scarth Combe in the Medico-Chirurgical Society of Edinburgh Transactions, under the heading The History of Anemia Cases .
However, this was not investigated in more depth until 1849, by British physician Thomas Addison, from which he obtained the common name of Addison's anemia. In 1871, German physician Michael Anton Biermer (1827-1892) noticed the particular characteristics of anemia in one of his patients; he then coined the term "progressive pernicious anemia". In 1907, Richard Clarke Cabot reported a series of 1,200 patients with PA; Their average survival is between one and three years. William Bosworth Castle experimented where he ingested raw hamburger meat and spewed it after an hour, and then put it in a group of 10 patients. Unprocessed raw hamburger meat is fed to the control group. The first group shows the response of the disease, while the latter group does not. This is not an ongoing practice, but shows the 'intrinsic factor' of stomach juice.
Pernicious anemia was a deadly disease before about 1920, when George Whipple suggested raw liver as a treatment. The first treatment that can be done for anemic anemia begins when Whipple makes the discovery in experimental journeys where he makes dogs anemia, then feeds them various foods to see which will make them recover the most quickly (he seeks care for anemia from bleeding, not pernicious anemia). Whipple found ingesting large amounts of the liver apparently to cure anemia from blood loss, and attempting liver consumption as a treatment for pernicious anemia, reported an increase there, too, in a paper in 1920. George Minot and William Murphy then began to isolate curative properties in the liver , and in 1926 showed it was contained in raw liver juice (in the process also showed it was iron in liver tissue, not a soluble factor in liver juice, which cures anemia from bleeding in dogs); thus, the discovery of the liver juice factor as a treatment for pernicious anemia by chance. Frieda Robscheit-Robbins is working with Whipple, co-authoring 21 papers from 1925-30. For the discovery of a cure from a previously fatal illness of unknown cause, Whipple, Minot, and Murphy shared the 1934 Nobel Prize in Medicine.
After Minot and Murphy verified the Whipple result in 1926, the victim of anemia pernisiaan eat or drink at least half a pound of raw liver, or drink raw liver juice, every day. This continues for several years, until concentrations of the juice of the liver are available. In 1928, chemist Edwin Cohn prepared a liver extract that was 50 to 100 times stronger than natural foods (liver). The extract can even be injected into the muscle, which means the patient no longer needs to eat a lot of liver or juice. It also reduces the cost of treatment significantly.
The active ingredient in the liver remained unknown until 1948, when it was isolated by two chemists, Karl A. Folkers from the United States and Alexander R. Todd of England. The substance is cobalamin, whose discoverer named vitamin B 12 . The new vitamins in the juice of the heart were finally completely purified and characterized in the 1950s, and other methods of producing it from the bacteria were developed. It can be injected into the muscles with less irritation, making it possible to treat the PA more easily. Pernicious anemia is finally treated with large oral oral doses of B 12 , usually between 1 and 4 mg daily.
One author has hypothesized that Mary Todd Lincoln, wife of American President Abraham Lincoln, had pernicious anemia for decades and died of it.
Research
SNAC complex
Although oral injections and intramuscular injection are the most common treatment methods available today, several new methods are being tested, with a high promise for future unification into mainstream treatment methods. Because injections are unfavorable vehicles for drug delivery, current research involves increased passive diffusion in ileum following oral ingestion of cobalamin derivatives. Researchers have recently taken advantage of a new compound of N- [8- (2-hydroxybenzoyl) amino] caprylate (SNAC), which greatly improves bioavailability and metabolic stability. SNAC is able to form a noncovalent complex with cobalamin while maintaining its chemical integrity. This complex is much more lipophilic than the water-soluble B vitamin 12 , so it can pass through cell membranes more easily.
Recombinant intrinsic factor
Another method to increase absorption through ileum is to swallow the Cbl complex that the IF has attached. The lack of intrinsic factor generated by the patient's body can be increased by using the synthetic human IF produced from recombinant pea plants. However, in cases where IF-antibodies are the reason for malabsorption throughout the ileum, this treatment will become ineffective.
Sublingual/intranasal Submission
Sublingual treatments have also been postulated to be more effective than oral treatments alone. A 2003 study found, while this method was effective, a dose of 500 g of cyanocobalamin was administered either orally or sublingually, equally efficacious in restoring normal cobalamin psychological concentration. The intranasal method has also been studied as a vehicle for cobalamin delivery. A 1997 study monitored plasma cobalamin concentrations from six patients with pernicious anemia for 35 days when treated with 1500? G intranasal hydroxocobalamin. One hour after administration, all patients showed an eight-fold increase in plasma cobalamin concentration and doubled after 35 days with three 1500 g treatments. However, further research is needed to investigate the long-term effectiveness of this delivery method.
Exploratory treatments
One exploration, and a potential alternative method for the treatment of pernicious anemia is the use of transdermal fillings. In one such system, patches consist of cyanocobalamin, stabilizer, and epidermal penetration enhancers. Transdermal routes allow cobalamin derivatives to spread passively through the stratum corneum, epidermis, and dermis, and eventually enter the bloodstream; Therefore, cobalamin avoids the first heart pass effect, and therefore offers the potential for increased bioavailability and efficacy. Slow release increases cobalamin part-time, offering the potential dose reduction required relative to oral delivery methods. In one such system, polycaprolactone-filled fibers made as nanofiber electrospun can release hundreds of micrograms of cobabalmin per day.
References
External links
- Vitamin B12 anemia deficiency in Curlie (based on DMOZ)
Source of the article : Wikipedia
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