1. Common Findings
1.1. PA develops slowly (possibly over 20 to 30 years); 60 years of age is the median age at time of diagnosis.
1.1.1. Because of the slow onset of symptoms, PA is usually severe by the time treatment is sought
1.2. Hemoglobin level has decreased significantly (7 to 8 g/dl), the individual experiences the
1.2.1. A low red blood cell count also can cause shortness of breath, dizziness, headache, coldness in your hands and feet, pale or yellowish skin, and chest pain.
1.3. Classic symptoms of Anemia
1.3.1. Weakness
1.3.2. Fatigue
1.3.3. Paresthesias of the feet and fingers
1.3.4. Difficulty in walking
1.3.5. Loss of appetite
1.3.6. Abdominal Pains
1.3.7. Weight Loss
1.3.8. Sore Tongue that is smooth and beefy red secondary to atrophic glossitis
1.4. "Lemon Yellow" skin due to combination of PALLOR and ICTERUS
1.5. HEPATOMEGALY (indicating right-sided heart failure)
1.6. SPLENOMEGALY
1.7. NEUROLOGICAL MANIFESTATIONS
1.7.1. produces neuronal death
1.7.1.1. resulting from nerve demyelination
1.7.2. Nerve Damage
1.7.3. Muscle weakness
1.7.4. tingling and numbness in your hands and feet
1.7.5. loss of reflexes
1.7.6. Confusion
1.7.7. Dementia
1.7.8. Memory Loss
1.8. SPINAL CORD ISSUES
1.8.1. loss of position and vibration sense
1.8.2. ataxia
1.8.3. spasticity
1.9. Affective Disorders
1.9.1. Depressive Types
1.10. DIGESTIVE TRACT PROBLEMS
1.10.1. Nausea and Vomiting
1.10.2. Heartburn
1.10.3. Abdominal Bloating and Gas
1.10.4. Constipation or Diarrhea
1.10.5. loss of appetite
1.11. People who have pernicious anemia also may be at higher risk for weakened bone strength and stomach cancer.
1.12. HEART PROBLEMS
1.12.1. Arrythmias
1.12.2. Heart Murmur
1.12.3. Enlarged Heart
1.12.4. Heart Failure
1.13. FRACTURES
1.13.1. Vitamin B12 deficiency can cause weakened bones and may lead to hip fractures.
1.14. PROBLEMS WITH INFANTS HAVING PA
1.14.1. Infants who have vitamin B12 deficiency may have poor reflexes or unusual movements, such as face tremors
1.14.2. They may have trouble feeding due to tongue and throat problems
1.14.3. If left untreated, Permanent Growth Problems
1.14.4. Irritable
2. Diagnostic Tests
2.1. Serologic studies
2.1.1. replaced the Schilling Test for dianosing PA
2.1.2. Measuring methylmalonic acid and homocysteine levels, which are elevated early in PA, is more sensitive.
2.1.3. The presence of circulating antibodies against parietal cells and intrinsic factor is also useful in diagnosis
2.1.4. Gastric biopsy reveals total achlorhydria (absence of hydrochloric acid), which is diagnostic for PA because it occurs only in the presence of this gastric lesion.
2.2. Bone Marrow Tests
2.2.1. Aspiration
2.2.2. Biopsy
2.3. CBC
2.3.1. Low hemoglobin and hematocrit
2.3.1.1. A low level of hemoglobin or hematocrit is a sign of anemia.
2.3.2. Mean Corpuscular Volume (MCV) is HIGH
2.3.2.1. MCV is a measure of the average size of your red blood cells. MCV can be a clue as to what's causing your anemia. In pernicious anemia, the red blood cells tend to be larger than normal.
2.3.3. low reticulocyte counts.
2.3.3.1. The test shows whether your bone marrow is making red blood cells at the correct rate
2.3.4. vitamin B12 level
2.3.5. homocysteine and methylmalonic acid (MMA) levels
2.3.5.1. High levels of these substances in your body are a sign of pernicious anemia.
2.3.6. intrinsic factor antibodies and parietal cell antibodies.
2.3.6.1. These antibodies also are a sign of pernicious anemia.
2.4. Gastric biopsy
3. Causative Factors
3.1. Congenital or acquired deficiency of intrinsic factor (IF); genetic disorder of DNA synthesis
3.1.1. Intrinsic factor is a protein made in the stomach. It helps your body absorb vitamin B12. In some people, an autoimmune response causes a lack of intrinsic factor.
3.1.2. is a genetic disorder that demonstrates an autosomal recessive inheritance pattern
3.2. PA is also frequently a component of autoimmune polyendocrinopathy, which is a cluster of autoimmune diseases of endocrine organs
3.2.1. Autoimmune Disease such as DIabetes Type 1
3.3. Most cases of PA result from an autoimmune gastritis (type A chronic gastritis) in which gastric atrophy results from destruction of parietal and zymogenic cells.
3.4. Crohn's Disease
3.5. Having part or all of your stomach or intestine taken out
3.6. HIV
3.7. Some medicines, like antacids or drugs that treat type 2 diabetes, can make it harder for your body to absorb enough B-12.
3.8. DIET
3.8.1. A strict vegetarian diet puts you at risk for PA too, since you won’t be eating foods that are rich in B-12 like eggs, milk, and poultry.
3.8.2. Breastfed infants of strict vegetarian mothers also are at risk for pernicious anemia. These infants can develop anemia within months of being born. This is because they haven't had enough time to store vitamin B12 in their bodies. Doctors treat these infants with vitamin B12 supplements.
3.8.3. elderly and people who suffer from alcoholism, also may be at risk for pernicious anemia. These people may not get the proper nutrients in their diets
3.9. Medications
3.9.1. Certain medicines that alter bacterial growth or prevent the small intestine from properly absorbing vitamin B12. Examples include antibiotics and certain diabetes and seizure medicines.
3.10. Surgery
3.10.1. A lack of intrinsic factor also can occur if you've had part or all of your stomach surgically removed. This type of surgery reduces the number of parietal cells available to make intrinsic factor.
3.11. INFECTIONS
3.11.1. A tapeworm infection. The tapeworm feeds off of the vitamin B12. Eating undercooked, infected fish may cause this type of infection.
3.11.2. Initiation of the autoimmune process may be secondary to a past infection with Helicobacter pylori
4. Risk Factors
4.1. Family clusters have been identified; 20% to 30% of individuals related to persons with PA also have PA.
4.1.1. These relatives, particularly first-degree female relatives, also demonstrate a higher frequency of the presence of gastric autoantibodies.
4.2. Initiation of the autoimmune process may be secondary to a past infection with Helicobacter pylori
4.3. more common in people of Northern European and African descent than in other ethnic groups.
4.3.1. Scandinavian, English, and Irish descent
4.3.2. Less common in individuals of Greek or Italian origin
4.3.3. Reported in Blacks and Hispanics
4.3.4. Females are more prone to develop PA, with black females having an earlier onset
4.4. Older people also are at higher risk
4.4.1. due to a lack of stomach acid and intrinsic factor, which prevents the small intestine from absorbing vitamin B12. As people grow older, they tend to make less stomach acid.
4.5. Have had part or all of your stomach surgically removed
4.6. Have an autoimmune disorder that involves the endocrine glands
4.6.1. such as Addison's disease, type 1 diabetes, Graves' disease, or vitiligo. Research suggests a link may exist between these autoimmune disorders and pernicious anemia that's caused by an autoimmune response.
4.7. Have certain intestinal diseases or other disorders that may prevent your body from properly absorbing vitamin B12
4.7.1. Examples include Crohn's disease, intestinal infections
4.8. Take medicines that prevent your body from properly absorbing vitamin B12
4.8.1. Examples of such medicines include antibiotics and certain seizure medicines.
4.9. strict vegetarian/poor diet
5. Pathophysiologic Etiology
5.1. Decreased/ Deficiency in B12 (Cobalamin) for erythropoiesis
5.2. abnormal deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis in the erythroblast; premature cell death
5.3. In pernicious anemia, the body can't make enough healthy red blood cells because it doesn't have enough vitamin B12.
5.4. Without enough red blood cells to carry oxygen to your body, you may feel tired and weak. Severe or long-lasting pernicious anemia can damage the heart, brain, and other organs in the body.
5.5. Body makes antibodies that attack and destroy the parietal (pa-RI-eh-tal) cells. These cells line the stomach and make intrinsic factor. As a result of this attack, the stomach stops making intrinsic factor. Without intrinsic factor, your body can't move vitamin B12 through the small intestine, where it's absorbed. This leads to vitamin B12 deficiency.
5.6. the most common type of megaloblastic anemia, is caused by vitamin B12 deficiency, which is often associated with the end stage of type A chronic atrophic (congenital or autoimmune) gastritis ( due to INFLAMMATION and IMMUNITY factors)
5.6.1. Most cases of PA result from an autoimmune gastritis (type A chronic gastritis) in which gastric atrophy results from destruction of parietal and zymogenic cells.
5.6.1.1. Early in the disease process the gastric submucosa becomes infiltrated with inflammatory cells, including CD4 lymphocytes, eventually extending into the lamina propria and causing degeneration of the parietal and zymogenic cells
5.6.2. Thus, PA is secondary to autoimmune destruction of parietal cells, thus diminishing the production of IF, and the presence of autoantibodies that neutralize the capacity of remaining IF to transport vitamin B12
6. Treatments
6.1. Replacement of vitamin B12 (cobalamin) is the treatment of choice.
6.1.1. lifelong intramuscular (IM) vitamin B12 replacement
6.2. Initial injections of vitamin B12 are administered weekly until the deficiency is corrected, followed by monthly injections for the remainder of the individual’s life
6.3. recent experience has shown that higher doses of orally administered vitamin B12 will be absorbed across the small bowel and is beneficial.
6.4. A study by Chan, Low, and Lee (2016) found that oral vitamin B12 replacement at 1000 μg daily was adequate to replace vitamin B12 levels in patients with pernicious anemia. Oral vitamin B12 is an effective alternative to vitamin B12 IM injections.
6.5. eat foods fortified with vitamin B12 or take vitamin B12 supplements.
6.6. multivitamins and B-complex vitamin supplements.
6.7. A vitamin B12 nose gel and spray also are available
6.7.1. These products may be useful for people who have trouble swallowing pills, such as older people who have had strokes.
7. PROGNOSIS
7.1. Untreated PA is fatal, usually because of heart failure. Death occurs after a course of remissions and exacerbations lasting from 1 to 3 years.
8. TYPE of ANEMIA
8.1. Pernicious anemia is one of two major types of "macrocystic" or "megaloblastic" anemia.
8.1.1. These terms refer to anemia in which the red blood cells are larger than normal. (The other major type of macrocystic anemia is caused by folic acid deficiency.)