Pernicious anemia

URL of this page: http://www.nlm.nih.gov/medlineplus/ency/article/000569.htm

Pernicious anemia is a decrease in red blood cells that occurs when the body cannot properly absorb vitamin B12 from the gastrointestinal tract. Vitamin B12 is necessary for the proper development of red blood cells. Pernicious anemia is a type of megaloblastic anemia. See also: Anemia

Causes
The body needs vitamin B12 to make red blood cells. To provide vitamin B12 to your blood cells, you need to eat enough foods containing vitamin B12, such as meat, poultry, shellfish, eggs, and dairy products. To absorb vitamin B12, your body uses a special protein called intrinsic factor, which is released by cells in the stomach. The combination of vitamin B12 bound to intrinsic factor is absorbed in the last part of the small intestine. When the stomach does not make enough intrinsic factor, the intestine cannot properly absorb vitamin B12. Very rarely, infants and children are born without the ability to produce enough intrinsic factor, or the ability to absorb the combination of intrinsic factor and vitamin B12 in the small intestine. Pernicious anemia that occurs at birth (congenital) is inherited. You need the defective gene from each parent to get it. Common causes of pernicious anemia include:
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Weakened stomach lining (atrophic gastritis) The body's immune system attacking the cells that make intrinsic factor (autoimmunity against gastric parietal cells) or intrinsic factor itself

The disease begins slowly and may take decades to fully establish. Although the congenital form occurs in children, pernicious anemia usually does not appear before age 30 in adults. The average age at diagnosis is 60. Risk factors include:

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Symptoms
People with mild anemia may have no symptoms or very mild symptoms. More typical symptoms of vitamin B12 deficiency anemia include:
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Diarrhea or constipation Fatigue, lack of energy, or light-headedness when standing up or with exertion Loss of appetite Pale skin Problems concentrating Shortness of breath, mostly during exercise Swollen, red tongue or bleeding gums Nerve damage caused by vitamin B12 deficiency that has been present for a longer time may cause: o Confusion or change in mental status (dementia) in severe or advanced cases o Depression o Loss of balance o Numbness and tingling of hands and feet

Exams and Tests

Tests that may used to diagnose or monitor pernicious anemia include:
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Bone marrow examination (only needed if diagnosis is unclear) Complete blood count (CBC) Measurement of serum holotranscobalamin II Reticulocyte count Schilling test Serum LDH Serum methylmalonic acid (MMA) level Serum vitamin B12 level

Pernicious anemia may also affect the results of the following tests:
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Bilirubin Cholesterol test Gastrin Leukocyte alkaline phosphatase Peripheral smear TIBC

Vitamin B12 deficiency affects the appearance of cells that form on the outer surface of the body and line inner passageways (epithelial cells). An untreated woman may have a false positive Pap smear.

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Treatment
Monthly vitamin B12 injections are prescribed to correct the vitamin B12 deficiency. This therapy treats the anemia and may correct the neurological complications if taken early enough. In people with a severe deficiency, the injections are given more often at first. Some doctors recommend that elderly patients with gastric atrophy take vitamin B12 supplements by mouth in addition to monthly injections. There is also a preparation of vitamin B12 that may be given through the nose. For some people, taking vitamin B12 tablets by mouth in a very high dose can be an effective treatment. A well-balanced diet is essential to provide other elements for healthy blood cell development, such as folic acid, iron, and vitamin C.

Outlook (Prognosis)
The outcome is usually excellent with treatment. Any damage to nerves may be permanent, especially if treatment is not started within 6 months of when symptoms began.

Possible Complications
People with pernicious anemia may have gastric polyps, and they are at increased risk for gastric cancer and gastric carcinoid tumors. Brain and nervous system (neurological) problems may continue if treatment is delayed.

When to Contact a Medical Professional

Call your health care provider if you have symptoms of vitamin B12 deficiency.

Prevention
There is no known way to prevent this condition. However, with early detection and treatment of vitamin B12 deficiency, complications can be minimized.

Alternative Names
Macrocytic achylic anemia; Congenital pernicious anemia; Juvenile pernicious anemia; Vitamin B12 deficiency (malabsorption)

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Megaloblastic anemia
URL of this page: http://www.nlm.nih.gov/medlineplus/ency/article/000567.htm

Megaloblastic anemia is a blood disorder in which there is anemia with larger-than-normal red blood cells. Anemia is a condition in which the body does not have enough healthy red blood cells. Red blood cells provide oxygen to body tissues.

Causes
Megaloblastic anemia is usually caused by a deficiency of folic acid or vitamin B12. Other less common causes are:
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Alcohol abuse Certain inherited disorders Drugs that affect DNA, such as chemotherapy drugs Leukemia Myelodysplastic syndrome Myelofibrosis

Risk factors relate to the causes. See also:

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Anemia - B12 deficiency Folate-deficiency anemia Pernicious anemia

Symptoms
See:
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Anemia - B12 deficiency Folate-deficiency anemia Pernicious anemia

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Exams and Tests

For testing information, see:
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Anemia - B12 deficiency Folate-deficiency anemia Pernicious anemia

Treatment
The first goal is to diagnose the cause of the anemia. The treatment depends on the cause. Anemias related to specific vitamin deficiencies are discussed separately. See:

What is pernicious anemia? Anemia is a condition in which the body does not have a sufficient number of red blood cells or hemoglobin. Hemoglobin is present within red blood cells and is important for carrying oxygen to all tissues of the body. In males, anemia is typically defined as hemoglobin level of less than 13.5 gram/100ml, while in women, a hemoglobin level of less than 12.0 gram/100ml is considered to be indicative of anemia. These definitions may vary slightly depending on the source and the laboratory reference used. Pernicious is a term that means destructive, injurious or deadly. Pernicious anemia is a disease where large, immature, nucleated cells (megaloblasts, which are forerunners of red blood cells) circulate in the blood, and do not function as blood cells; it is a disease caused by impaired uptake of vitamin B-12 due to the lack of intrinsic factor (IF) in the gastric mucosa. It was termed "pernicious" because before it was learned that vitamin B-12 could treat the anemia, most people that developed the disease died from it. Anemia can result from disruptions in the production of red blood cells or hemoglobin as well as from an increased destruction of red blood cells or loss of blood. Pernicious anemia is due to an inability to absorb vitamin B-12 (also known as cobalamin or Cbl) from the gastrointestinal tract. Humans get vitamin B-12 from animal products; both meat and dairy products are dietary sources of vitamin B-12. The body is able to store vitamin B-12 for a long time, so inadequate dietary intake must persist for years before a true deficiency of vitamin B-12 is reached. Because of
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this, the symptoms of pernicious anemia usually do not appear for years. While pernicious anemia is most commonly diagnosed in adults with an average age of 60, a rare, congenital (inborn) type of pernicious anemia has been described. As with other causes of anemia, symptoms related to decreased oxygen-carrying capacity of the blood can include tiredness and shortness of breath. Vitamin B-12 deficiency also interferes with the function of the nervous system, and symptoms due to nervous system damage may be apparent even before the anemia is discovered. Pernicious anemia is most common in Caucasian persons of northern European ancestry than in other racial groups. In this population, 10-20 people per 100,000 persons are diagnosed each year with pernicious anemia. Pernicious anemia is also termed Biermer's or Addison's anemia.

What is megaloblastic anemia? Sometimes, anemias are subclassified based upon the size and microscopic appearance of the red blood cells. In this regard, pernicious anemia is a form of megaloblastic anemia. Megaloblastic anemia refers to an abnormally large type of
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red blood cell (megaloblast). Megaloblasts are produced in the bone marrow when vitamin B-12 or folic acid levels are low. Megaloblastic anemia can also be caused by other disease of the bone marrow and can be a side effect of some cancer chemotherapy drugs.
What causes pernicious anemia?

Pernicious anemia is considered to be an autoimmune disease, in which the body's own immune system mistakenly damages its own tissues. It is believed that the decreased absorption of vitamin B-12 from the gastrointestinal tract in pernicious anemia results from the presence of an autoantibody against intrinsic factor (IF), a protein made in the stomach that is necessary for the absorption of vitamin B-12. Normally, vitamin B-12 binds to intrinsic factor in the stomach, and this facilitates its absorption by the small intestine further along in the digestive process. Along with the autoimmune process that attacks the IF protein and lowers IF levels in stomach secretions, another autoimmune reaction against the stomach lining cells also occurs, resulting in a form of inflammation known as chronic atrophic gastritis. Pernicious anemia is sometimes associated with other autoimmune diseases such as Graves' disease, Hashimoto's thyroiditis and vitiligo (depigmentation or blanching of skin areas). Is pernicious anemia the same as vitamin B-12 deficiency anemia? Pernicious anemia is one form of vitamin B-12 deficiency that results from the autoimmune process described above. However, other causes of vitamin B-12 deficiency can also produce the same signs and symptoms as pernicious anemia. Other potential causes of vitamin B-12 deficiency include surgical removal of the stomach or a portion of the stomach (total or partial gastrectomy), other gastrointestinal diseases such as celiac disease or Crohn's disease, infections of the gastrointestinal tract, and poor nutrition.
What are the symptoms of vitamin B-12 deficiency/ pernicious anemia?

As discussed previously, true pernicious anemia results from an autoimmune condition that impairs absorption of dietary vitamin B-12, resulting in vitamin B-12 deficiency. Vitamin B-12 deficiency of any cause will result in anemia and neurologic symptoms. Because the body has large stores of vitamin B-12, a deficiency takes many years to establish.
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Vitamin B-12 deficiency affects the nervous system, leading to a variety of symptoms. Sometimes, these may be apparent before symptoms related to the anemia. Neurological symptoms vary and may be nonspecific (meaning that these are symptoms that can be caused by a number of different conditions). Feelings of numbness, tingling, weakness, lack of coordination, clumsiness, impaired memory, and personality changes can all occur. Both sides of the body are usually affected, and the legs are typically more affected than the arms. A severe deficiency can result in more serious neurological symptoms, including severe weakness, spasticity, paraplegia, and fecal and urinary incontinence. Symptoms of anemia are due to the reduced oxygen-carrying capacity of the blood. Shortness of breath, fatigue, dizziness, and pale skin can all occur with anemia. In anemia, the heart is placed under stress since it has to work harder to deliver enough oxygen to body tissues. This can result in heart murmurs, fast heartbeats, arrhythmias, an enlarged heart (cardiomegaly), or even heart failure. It is important to note that not all people who have vitamin B-12 deficiency and neurological symptoms will also have anemia. A deficiency of vitamin B--12 can also alter the surface of the tongue, making it appear shiny or smooth. Finally, sometimes pernicious anemia is diagnosed in a patient with no symptoms. In these cases, it is usually found incidentally when blood tests are ordered for another reason.
How is pernicious anemia/vitamin B-12 deficiency diagnosed?

The first step is always a thorough history and physical examination by a health care practitioner. The results of this examination are used to help direct further testing. A number of laboratory tests are available that can help diagnose pernicious anemia as well as other causes of vitamin B-12 deficiency. These tests include:
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A complete blood cell count (CBC) Examination of a blood smear (peripheral smear) under a microscope, often performed in association with a CBC Blood vitamin B-12 level measurements Tests for the presence of autoantibodies to intrinsic factor or stomach lining cells
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Blood levels of iron and iron-binding capacity Folate levels (which are often reduced when vitamin B-12 levels are low) Blood levels of methylmalonic acid or homocysteine, both of which may be sensitive indicators of vitamin B-12 deficiency The Schilling test, a measure of how well the body can absorb vitamin B-12, is less commonly used today than in the past. Finally, bone marrow aspiration or bone marrow biopsy may be recommended in some cases if bone marrow disorders are suspected

What is the treatment for pernicious anemia and vitamin B-12 deficiency? The symptoms of pernicious anemia and vitamin B-12 deficiency can be treated by replenishing the vitamin B-12 supply in the body. If a condition other than pernicious anemia is responsible for vitamin B-12 deficiency, treatment must also be directed at the underlying condition. Symptoms of vitamin B-12 deficiency may be improved after just a few days of medical treatment. Vitamin B-12 is typically given as an intramuscular injection (shot). An injection of 1000 micrograms (1 mg) of vitamin B-12 is generally given every day for one week, followed by 1 mg every week for four weeks and then 1 mg every month thereafter. Alternative treatments for pernicious anemia include high-dose oral vitamin B-12, since a lower-efficiency absorption system for vitamin B-12 exists in the intestine that does not require the presence of IF. However, the oral dose required for this type of therapy (1 to 2 milligrams/day) is more than 200 times higher than the minimum daily vitamin B-12 requirement for adults and is significantly higher than that available in most standard multivitamins and B-12 supplements. Nasal spray and sublingual (under the tongue) preparations of vitamin B-12 are also available and are under investigation Can pernicious anemia/ vitamin B-12 deficiency be prevented? The autoimmune process that causes pernicious anemia cannot be prevented. Vitamin B-12 deficiency that is caused by conditions such as other gastrointestinal diseases and gastrointestinal surgery is preventable only to the extent that these causative conditions themselves are preventable.

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Vitamin B-12 is derived from animal (for example, meat, fish, poultry, milk) sources, but vitamin B-12 deficiency in vegetarians or vegans can be prevented by the use of oral vitamin B-12 supplements. An oral dose of 100-200 micrograms (mcg) taken weekly is sufficient. Pregnant and nursing women who are vegetarians or vegan should take a B-12 supplement and inform their doctors they are vegetarians or vegan. What is the prognosis for pernicious anemia/ vitamin B-12 deficiency? If untreated, the neurological complications of pernicious anemia can be permanent and end in death, but pernicious anemia is easily and effectively treated by the administration of vitamin B-12. Life-long treatment is required. People with pernicious anemia have a slightly increased risk of stomach cancer when compared to the normal population. The incidence of stomach cancer in people with pernicious anemia is 2-3 times higher than in the general population of the same age. Pernicious Anemia At A Glance
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Pernicious anemia is a condition caused by too little vitamin B12 in the body. It is a form of vitamin B12 deficiency anemia. Vitamin B12 helps the body make healthy red blood cells and helps keep nerve cells healthy. It is found in animal foods, including meat, fish, eggs, milk, and other dairy products. The most common cause of pernicious anemia is the loss of stomach cells that make intrinsic factor. Intrinsic factor helps the body absorb vitamin B12 in the intestine. The loss of parietal cells may be due to destruction by the body's own immune system. Pernicious anemia can cause permanent damage to nerves and other organs if it goes on for a long time without being treated. It also raises the risk for developing stomach cancer. Common signs and symptoms of pernicious anemia are:
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Feeling tired and weak Tingling and numbness in hands and feet

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A bright red, smooth tongue

Pernicious anemia is diagnosed using family history and medical history, a physical exam, and diagnostic tests and procedures. Pernicious anemia is easy to treat with vitamin B12 pills or shots as well as diet changes. Life-long treatment is needed. Complications caused by untreated pernicious anemia may be reversible with treatment. Doctors don't know how to prevent pernicious anemia that is caused by the immune system destroying stomach cells. Eating foods high in vitamin B12 and folic acid can help prevent vitamin B12 deficiency caused by a poor diet

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