Pernicious Anemia

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Pernicious Anemia by Mind Map: Pernicious Anemia

1. Pathophysiologic Etiology

1.1. Although pernicious anemia technically refers to cases resulting from not enough intrinsic factor, it is often used to describe all cases of anemia due to not enough vitamin B12.

1.2. Body is unable to make enough healthy red blood cells because it doesn't have enough vitamin B12, a nutrient necessary to make healthy red blood cells.

1.2.1. Vitamin B12 binds to intrinsic factor in the stomach, and this facilitates its absorption later when digestive products pass through the small intestine. Intrinsic factor is produced by parietal cells of the gastric mucosa and the intrinsic factor-B12 complex is absorbed by cubilin receptors on the ileum epithelial cells.

1.3. B12 is required by enzymes for two reactions: the conversion of methylmalonyl CoA to succinyl CoA, and the conversion of homocysteine to methionine.

1.3.1. During B12 deficiency, this reaction cannot proceed, which leads to the accumulation of 5-methyltetrahydrofolate and depletes the other types of folate required for purine and thymidylate synthesis. This leads to inhibition of DNA replication in red blood cells, and results in the formation of large, fragile megaloblastic erythrocytes.

2. Causative Factors

2.1. Impaired vitamin B12 absorption

2.1.1. An autoimmune condition in which the body's immune system attacks the actual intrinsic factor protein or the cells in the lining of your stomach that make it.

2.2. 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.

2.3. Weakened stomach lining (atrophic gastritis)

2.4. Diet lacking enough vitamin B12 intake.

2.4.1. Foods high in vitamin B12 include: Breakfast cereals with added vitamin B12 Meats such as beef, liver, poultry, and fish Eggs and dairy products Foods fortified with vitamin B12, such as soy-based beverages and vegetarian burger.

2.5. Very rarely, pernicious anemia is passed down through families and is called congenital pernicious anemia. This is an autosomal recessive disorder. Babies with this type of anemia do not make enough intrinsic factor.

3. Risk Factors

3.1. More common in Northern European or African descent

3.2. Have a family history of the condition

3.3. Atoimmune disorder that involves the endocrine glands, such as Addison's disease, type 1 diabetes, Graves' disease, or vitiligo

3.4. Surgery on stomach or small intestine. The stomach makes intrinsic factor, which helps your body absorb vitamin B12. The small intestine is where vitamin B12 is absorbed.

3.5. Intestinal diseases or other disorders that may prevent vitamin B12 absorption. Examples include Crohn's disease, intestinal infections, and HIV.

3.6. Take medicines that prevent your body from properly absorbing vitamin B12, such as antibiotics and certain seizure medicines.

3.7. Environmental conditions, such as smoking, excessive alcohol or hot tea ingestion

4. Diagnostic Tests

4.1. Blood tests: complete blood count, reticulocyte count, methylmalonic acid and homocysteine level, vitamin B12 level

4.2. Antibody tests for intrinsic factor antibodies and parietal cell antibodies

4.3. Bone marrow examination (only needed if diagnosis is unclear)

4.4. Schilling test to determine whether your stomach is producing intrinsic factor

4.5. Gastric biopsy

5. Common Findings

5.1. Fatigue, lack of energy, or lightheadedness when standing up or with exertion

5.2. Shortness of breath, mostly during exercise

5.3. Problems concentrating

5.4. Swollen, red tongue (glossitis) or bleeding gums

5.5. Paresthesias of feet and fingers

5.6. Chest pain or arrhythmias

5.7. Pale or yellow-ish skin

5.8. Loss of appetite

5.9. Desire to eat ice or other non-food things (pica)

5.10. Diarrhea or constipation

6. Treatments

6.1. The goal of treatment is to increase your vitamin B12 level.

6.2. Treatment involves vitamin B12 injections. People with severely low levels of B12 may need weekly injections until the deficiency is corrected, then they may receive monthly injections.

6.3. Some people may also need to take vitamin B12 supplements by mouth or intranasally.

6.4. Your provider will also recommend eating a variety of foods.

6.5. If medicines are the cause of your pernicious anemia, your doctor may change the type or dose of medicine you take.

6.6. Infants of strict vegetarian mothers may be given vitamin B12 supplements from birth.

7. References

7.1. McCance, K.L., Huether, S. (2014). Pathophysiology: The Biologic Basis for Disease in Adults and Children, 7th edition. St Louis, MO: Elsevier.

7.2. Neumann, W. L., Coss, E., Rugge, M., & Genta, R. M. (2013). Autoimmune atrophic gastritis--pathogenesis, pathology and management. Nature Reviews.Gastroenterology & Hepatology, 10(9), 529-541. doi:

7.3. Toh, B. (2017). Pathophysiology and laboratory diagnosis of pernicious anemia. Immunologic Research, 65(1), 326-330. doi:

8. Autoimmunity & Inflammation

8.1. Decreased absorption of vitamin B-12 is an autoimmune process in which the body's immune system attacks the lining of the stomach.

8.1.1. Antibodies are produced against intrinsic factor. The autoimmune process attacks the IF protein and lowers IF levels in stomach secretions.

8.2. An autoimmune process directed at the stomach lining cells also occurs and results in chronic atrophic gastritis, which is characterized by stomach atrophy and the presence of antibodies to parietal cells and intrinsic factor.

8.2.1. Inflammatory cells degenerate parietal and zymogenic cells, which are replaced by mucous-containing cells. This results in the deficiency of all secretions (hydrochloric acid, pepsin, and IF) in the stomach. Progresses from a mild chronic inflammation of the gastric corpus to pernicious anemia as consequence of intrinsic factor loss and neutralizing intrinsic factor antibody that impairs cobalamin absorption.