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Vitamin B12 is found in many animal products such as meat, fish, dairy, and eggs. The daily requirements of vitamin B12 are between 2 to 3 micrograms. Vitamin B12 helps to regulate the immune system's response to infection and is an essential part of many metabolic functions, including the following; • the production and maturation of red blood cells which are pivotal for health due to their function of delivering oxygen throughout the body. • the synthesis of new DNA, It is important for cell growth and division. • the production of the building blocks that make up DNA. Vitamin B12 also plays several roles in the functioning and maintenance of the nervous system. • It is essential for the production of neurotransmitters; these are the chemicals which allow signals to be passed along the nervous system. • It is also a component in the synthesis and repair of the myelin sheath, which is wrapped around nerves and is necessary for the fast transmission of signals along nerve cells. Up to 5% of ingested vitamin B12 can be absorbed through simple diffusion, the other 95% must bind with a protein called intrinsic factor before it can be absorbed in the ileum region of the small intestine. intrinsic factor is crucial for the transport and absorption of vitamin B12. Intrinsic factor is produced in parietal cells. These cells are located in glands lining the body and fundus regions of the stomach. The parietal cells also produce hydrochloric acid. The acidic environment of the stomach helps in the following ways; • Its aids digestion and absorption of minerals such as iron, calcium, and phosphate. • It activates digestive enzymes. • It kills many bacteria which are ingested with food. Intrinsic factor binds to vitamin B12 in the stomach and promotes its transport to the small intestine. The body absorbs the intrinsic factor and vitamin B12 complex in the ileum. The ileum is lined with receptors which can absorb the complex created by vitamin B12 combined with intrinsic factor . The receptors can recognise the vitamin B12 when bound to intrinsic factor and will engulf it, absorbing it from the ileum. The unbound vitamin B12 will not be recognised or absorbed by the receptors. Pernicious anaemia is a vitamin B12 deficiency which occurs as the result of autoimmune activity. The immune system produces antibodies which cause damage to intrinsic factor or to the parietal cells which produce it. Antibodies are immune proteins which recognise and neutralise foreign substances, such as bacteria and viruses. In autoimmune conditions, the immune system produces antibodies that attack aspects of a person’s own body, this can result in damage or destruction of normal, healthy cells. In pernicious anaemia, the body produces antibodies which are either; • Intrinsic factor antibodies • Or; Parietal cell antibodies Both of these types of antibodies will result in the impairment of intrinsic factor, and therefore a deficiency of vitamin B12. There are two types of intrinsic factor antibodies, these prevent the action of intrinsic factor in different ways. • Type 1 antibodies block the binding of intrinsic factor and vitamin B12. • Type 2 antibodies prevent the bound intrinsic factor and vitamin B12 from attaching to the receptors in the small intestine, this prevents it from being absorbed. Parietal cell antibodies destroy the parietal cells themselves. The parietal cells produce intrinsic factor; therefore destruction of the parietal cells leads to a lack of intrinsic factor. The destruction of parietal cells can result in additional complications, as in addition to intrinsic factor the parietal cells produce the stomach’s hydrochloric acid. The decrease in stomach acidity can compromise the digestion of proteins and can lead to iron deficiency. Pernicious anaemia is responsible for 20 to 50% of cases of vitamin B12 deficiency. Pernicious anaemia affects equivalent to 1 in every 1000 people. Pernicious anaemia can affect people of all ages; however, prevalence increases with age. Approximately 3% of people over 65 develop pernicious anaemia. Pernicious anaemia is more common in women than it is in men. With twice as many women being diagnosed with the disease compared to males The number of people with pernicious anaemia may be significantly higher than currently identified. This is due to several factors; • The disease is pernicious in nature, it can take many years for symptoms to develop, and the onset can be gradual . This is due to the liver’s capacity to store excess vitamin B12. The liver can potentially store enough vitamin B12 to last for 5 to 10 years. • Pernicious anaemia can present with a myriad of symptoms and can present very differently across different patients. This can make a diagnosis difficult. • There is no ‘gold standard’ test for pernicious anaemia, making it difficult to diagnose the condition conclusively. The reason that some people develop pernicious anaemia is currently uncertain and requires further research, current evidence suggests that the following may play a role; • Pernicious anaemia clusters in families, which suggests that there is a possible genetic factor. • Helicobacter Pylori is a bacteria which can infect the stomach. A current theory is that Helicobacter Pylori has a similar structure to intrinsic factor and parietal cells. Therefore when the immune system is fighting the Helicobacter Pylori infection, the antibodies that it creates may also target the intrinsic factor and parietal cells. The presentation of symptoms is highly variable in cases of pernicious anaemia. There is also the potential that symptoms can come on gradually in such a way that people become accustomed to the symptoms over time. The most common initial symptom is a pins and needles, sensation. This usually occurs in the hands, arms, or legs. The typical presentation of pernicious anaemia includes; • Pins and needles • fatigue • pale appearance • alterations to vision and smell • headache • chest palpitations • chest pain. The impact upon the brain and nervous system could potentially cause the following symptoms; • urinary incontinence. • muscle weakness. • imbalance • unsteady gait • clumsiness • muscle stiffness • Depression • Mania • Psychosis • auditory or visual hallucinations • memory issues • decreased mental concentration. Risks linked to pernicious anaemia include; • An increased risk of developing gastric cancer. People with pernicious anaemia should be vigilant in monitoring potential gastric symptoms and speaking to their doctor if they have any of the following: heartburn, problems swallowing, indigestion, stomach pain, and feeling full when eating. • People with pernicious anaemia also have an increased chance of developing other autoimmune conditions - such as thyroid disorders, rheumatoid arthritis, and type 1 diabetes. If someone is suspected of having pernicious anaemia, then the following blood tests may be carried out. Mean corpuscular volume analysis. The Mean corpuscular volume is a measurement of the size and volume of red blood cells. Pernicious anaemia often results in megaloblastic anaemia in which fewer red blood cells are formed and they are larger in size than is typical. A blood sample is taken and the Mean corpuscular volume is measured, if this value is larger than normal then it is indicative of possible pernicious anaemia. However, this test is not definitive as red blood size appears normal in 30% of people with pernicious anaemia . The levels of vitamin B12 in blood serum can also be used as a diagnostic test for pernicious anaemia. If levels of cobalamin in the blood are below 200 nanograms per litre then this is indicative of pernicious anaemia. Levels between 200 and 400 nanograms per litre are considered borderline levels. Testing for the presence of intrinsic factor antibodies in blood is a further available diagnostic test. This test is not particularly sensitive, the intrinsic factor antibodies are only successfully detected in around 50 to 70% of cases of pernicious anaemia, meaning that a negative results does not necessarily rule out a diagnosis of pernicious anaemia. The presence of parietal cell antibodies in blood can also be tested for. These antibodies are successfully found via testing in 85% of patients making this a highly sensitive test. However the test is not highly specific and positive results can be returned when antibodies for other autoimmune conditions are present, this can result in a false positive for pernicious anaemia. The underlying lack of intrinsic factors can’t be cured. However, vitamin B12 deficiency can be managed effectively with lifelong vitamin B12 administration. A manufactured form of vitamin B12 called Hydroxocobalamin is used for treatment. For people with neurological symptoms the treatment regimen is; Intramuscular injection of 1mg of hydroxocobalamin every other day until there is no further improvement. Then Intramuscular injection of 1mg of hydroxocobalamin every 2 months. For people without neurological symptoms the treatment regimen is; Intramuscular injection of 1mg of hydroxocobalamin every 2 months. serious side effects are very rare. some potential side effects of the treatment include; • Pain or irritation at the injection site • Diarrhea • Nausea • Vomiting • Headache • Hot flushes. Pernicious anaemia can be well controlled through regular administration of hydroxocobalamin, patients usually respond very well to the treatment. If pernicious anaemia is left untreated then there is the potential that some symptoms could become irreversible.