Pernicious Anemia (PA)

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Pernicious Anemia (PA) by Mind Map: Pernicious Anemia (PA)

1. Pathophysiologic etiology

1.1. Associated with type A chronic atrophic (autoimmune) gastritis (McCance & Rote, 2019)

1.1.1. The presence of PA with autoimmune gastritis leads to gastric atrophy from destruction of parietal and zymogenic cells and is marked by circulating parietal cell antibody to gastric H/K ATPase. (McCance & Rote, 2019; Toh, 2017)

1.1.1.1. This results in a deficiency of all secretions of the stomach including:

1.1.1.1.1. Hydrochloric acid

1.1.1.1.2. Pepcid

1.1.1.1.3. IF

1.1.1.1.4. (McCance & Rote, 2019)

1.1.2. Impairs the production of intrinsic factor (IF); a requirement for vitamin B12 uptake from the gut (McCance & Rote, 2019)

1.1.2.1. Vitamin B12 deficiency occurs as a result of a decreased dietary intake of said vitamin or an absorption impairment of intrinsic factor as a result of gastric atrophy (Abdulmanea, Alsaeed, Shaik & AlGahtani, 2014)

1.1.3. The gastritis arises from activation of pathologic Th1 CD4 T cells to gastric H/K ATPase that is present normally on gastric mucosal secretory membranes (Toh, 2017)

1.2. Pernicious anemia is a manifestation of chronic atrophic gastritis that affects the corpus of the stomach that removes the gastric mucosa of gastric parietal cells (Toh, 2017)

1.3. The principal disorder in PA is an absence of intrinsic factor IF (McCance & Rote, 2019)

1.3.1. IF is secreted by gastric parietal cells and complexes with dietary vitamin B12 in the small intestine (McCance & Rote, 2019)

1.3.2. The B12-IF complex binds to cell surface receptors in the ileum and is transported across intestinal mucosa (McCance & Rote, 2019)

1.4. Deficiency in the secretion of IF may be congenital; however, is often an autoimmune (and possibly innate) process that is directed against gastric parietal cells (McCance & Rote, 2019)

1.4.1. Congenital IF deficiency is a genetic disorder that portrays an autosomal recessive inheritance pattern (McCance & Rote, 2019)

1.4.1.1. The autoimmune form may have a genetic component, but not a genetic pattern of transmission (McCance & Rote, 2019)

1.5. PA is also a component of autoimmune polyendocrinopathy; a group of autoimmune diseases of endocrine organs (e.g. autoimmune thyroiditis and type 1 diabetes mellitus) (McCance & Rote, 2019; Toh, 2017)

2. Causative factors

2.1. o surgical removal of the stomach

2.2. o resection of the ileum

2.3. o tape worm infestation

2.4. (McCance & Rote, 2019)

2.5. Other conditions that have an increased demand for vitamin B12 such as:

2.5.1. o pregnancy

2.5.2. o hyperthyroidism

2.5.3. o chronic infection

2.5.4. o disseminated cancer

2.5.5. (McCance & Rote, 2019)

2.6. Individuals experience classic symptoms of PA when hemoglobin levels are decreased significantly (7 to 8 g/dL): (McCance & Rote, 2019)

2.6.1. o Weakness

2.6.2. o Fatigue

2.6.3. o Paresthesia of the feet and fingers

2.6.4. o Difficulty walking

2.6.5. o Loss of appetite

2.6.6. o Abdominal pains

2.6.7. o Weigh loss

2.6.8. o Sore tongue that is smooth and beefy red secondary to atrophic glossitis

2.6.9. o Skin becomes a lemon yellow

2.6.10. o Hepatomegaly and splenomegaly in the elderly

2.6.11. (McCance & Rote, 2019)

3. Risk factors

3.1. Affects individuals 30 years and older with 60 years being the average age of diagnosis (McCance & Rote, 2019)

3.2. Northern European descent; however, is becoming recognizable among all populations and ethnic groups (McCance & Rote, 2019)

3.3. Environmental conditions may contribute: (McCance & Rote, 2019)

3.3.1. o Excessive alcohol

3.3.2. o Hot tea ingestion

3.3.3. o Smoking

3.3.4. (McCance & Rote, 2019)

4. Diagnostic tests

4.1. Clinical manifestations

4.2. Blood Tests

4.3. Bone marrow aspiration

4.4. Serologic studies

4.5. Gastric biopsy

4.5.1. Reveals achlorhydria; a diagnostic of PA as it only occurs with the presence of a gastric lesion (McCance & Rote, 2019)

4.6. The presence of circulating antibodies against parietal cells and IF

4.7. (McCance & Rote, 2019; Toh, 2017)

4.8. The following tests diagnose PA:

4.8.1. Moderate to severe megaloblastic anemia

4.8.2. Leukopenia with hypersegmented granulocytes

4.8.3. Decreased levels of serum vitamin B12

4.8.4. Elevated serum levels of homocysteine and methylmalonic acid

4.8.5. Increased reticulocytes and an increase in the hematocrit level after 5 days of vitamin B12 parenteral administration

4.8.6. (McCance & Rote, 2019; Toh, 2017)

5. Common findings

5.1. Asymptomatic autoimmune gastritis that is chronic precedes the onset of corpus atrophy by 10–20 years; thereby, PA develops slowly overtime at about 20 to 30 years (McCance & Rote, 2019; Toh, 2017)

5.2. Due to slow progression of disease and symptoms, PA is usually severe by the time treatment is pursued (McCance & Rote, 2019)

5.3. Early symptoms are ignored due to vagueness and decreased specificity (McCance & Rote, 2019)

5.3.1. Early symptoms include infections, mood swings, and gastrointestinal, cardiac, and/or kidney ailments (McCance & Rote, 2019)

5.3.1.1. Undiagnosed cases of PA can lead to severe health problems; therby leading to permanent damage to vital organs such as the nerves, heart and other parts of the body (Abdulmanea, Alsaeed, Shaik & AlGahtani, 2014)

5.4. Along with clinical manifestations, there are neurologic manifestations; result from nerve demyelination that produces neuronal death (McCance & Rote, 2019)

5.4.1. Columns of the spinal cord may be affected, causing loss of position and vibration sense, ataxia, and spasticity (McCance & Rote, 2019)

5.5. Low levels of vitamin B12 have been associated with neurocognitive disorders and include: (McCance & Rote, 2019)

5.5.1. o Encephalopathy

5.5.2. o Myelopathy

5.5.3. o Peripheral and optic neuropathy

5.5.4. (McCance & Rote, 2019

5.6. Individuals with Alzheimer’s disease have shown to have vitamin B12 deficiency (McCance & Rote, 2019)

5.7. Individuals with atrophy and metaplasia of gastric mucosa associated with PA have a greater risk of developing gastric carcinoma (McCance & Rote, 2019)

5.8. Acid loss leads to iron deficiency anemia that precedes B12 deficiency pernicious anemia by 20 years (Toh, 2017)

6. Treatments

6.1. The treatment of choice is the replacement of vitamin B12; whereby, injections are delivery weekly until the deficiency is corrected, and then monthly for the remainder of an individual’s life (McCance & Rote, 2019)

6.1.1. Effectiveness is determined by the increase in reticulocyte count (McCance & Rote, 2019)

6.2. High doses of orally administered B12 absorbed across the small bowel are also beneficial (McCance & Rote, 2019)

7. Immunity, Inflammation, Infection or Injury

7.1. Individuals with PA have autoantibodies against the gastric H+ -K+ ATPase; the major protein constituent of parietal cell membranes (McCance & Rote, 2019)

7.2. Early in the disease process, the gastric submucosa becomes infiltrated with inflammatory cells including autoreactive T cells (McCance & Rote, 2019)

7.2.1. The T cell response initiates gastric mucosa injury and triggers the formation of autoantibodies (McCance & Rote, 2019)

7.2.2. Susceptibility to PA development has a genetic link to variants involving the inflammasome, suggesting an innate immunity relationship (McCance & Rote, 2019)

7.3. A past infection with Helicobacter pylori may be cause for initiation of the autoimmune process (McCance & Rote, 2019)

7.3.1. Although H. pylori infection is rare in individuals with PA, greater than half of these individuals possess circulating antibodies against this organism; thus, suggesting past history of infection (McCance & Rote, 2019)

8. Pernicious Anemia

8.1. Pernicious definition; highly injurious or destructive Type of megaloblastic anemia Caused by vitamin B12 deficiency (McCance & Rote, 2019)

8.2. PA is a chronic illness where body fails to produce normal and healthy red blood cells as a result of a vitamin B12 deficiency; B12 is required for normal cell growth (Abdulmanea, Alsaeed, Shaik & AlGahtani, 2014)

8.3. Pernicious anemia is a manifestation of chronic atrophic autoimmune gastritis that affects the corpus of the stomach that removes the gastric mucosa of gastric parietal cells (Toh, 2017)

9. Gastric parietal cells produce two essential biologics: intrinsic factor and HCl acid (Toh, 2017)

10. Pernicious anemia is a consequence of intrinsic factor loss and neutralizing intrinsic factor antibody that impairs cobalamin absorption (Toh, 2017)