Pernicious anemia

Pernicious anemia, also known as Addison’s anemia, is a megaloblastic anemia characterized by decreased gastric production of hydrochloric acid and deficiency of intrinsic factor (IF), a substance normally secreted by the parietal cells of the gastric mucosa that’s essential for vitamin B₁₂ absorption in the ileum. The resulting deficiency of vitamin B₁₂ causes serious neurologic, gastric, and intestinal abnormalities. Untreated pernicious anemia may lead to permanent neurologic disability and death.

Causes and incidence

Familial incidence of pernicious anemia suggests a genetic predisposition. (It may involve an inherited single dominant autosomal factor.) Significantly higher incidence in patients with immunologically related diseases, such as thyroiditis, myxedema, and Graves’disease, seems to support a widely held theory that an inherited autoimmune response causes gastric mucosal atrophy and, therefore, deficiency of hydrochloric acid and IF. IF deficiency impairs vitamin B₁₂ absorption. The resultant vitamin B₁₂ deficiency inhibits cell growth, particularly of red blood cells (RBCs), leading to insufficient and deformed RBCs with poor oxygen-carrying capacity. It also impairs myelin formation, causing neurologic damage. Iatrogenic induction can follow partial gastrectomy.

PEDIATRIC TIP Juvenile pernicious anemia, occurring in children younger than age 10, stems from a congenital stomach disorder that causes secretion of abnormal IF.

ELDER TIP With age, vitamin B₁₂ absorption may also diminish, resulting in reduced erythrocyte mass and decreased hemoglobin (Hb) levels and hematocrit (HCT).

Pernicious anemia primarily affects people of northern European ancestry. It’s rare in children and infants. Onset typically occurs after age 35, and incidence increases with age. It affects about 2% of people older than age 60.

Signs and symptoms

Characteristically, pernicious anemia has an insidious onset but eventually causes an unmistakable triad of symptoms: weakness, sore tongue, and numbness and tingling in the extremities. The lips, gums, and tongue appear markedly bloodless. Hemolysis-induced hyperbilirubinemia may cause faintly jaundiced sclera and pale to bright yellow skin. In addition, the patient may become highly susceptible to infection, especially of the genitourinary tract.

Other systemic symptoms of pernicious anemia include the following:

❑ GI: Gastric mucosal atrophy and decreased hydrochloric acid production disturb digestion and lead to nausea, vomiting, anorexia, weight loss, flatulence, diarrhea, and constipation. Gingival bleeding and tongue inflammation may hinder eating and intensify anorexia.

❑ Central nervous system (CNS): Demyelination caused by vitamin B₁₂ deficiency initially affects the peripheral nerves but gradually extends to the spinal cord. Consequently, the neurologic effects of pernicious anemia may include neuritis; weakness in extremities; peripheral numbness and paresthesia; disturbed position sense; lack of coordination; ataxia; impaired fine finger movement; positive Babinski’s and Romberg’s signs; light-headedness; altered vision (diplopia and blurred vision), taste, and hearing (tinnitus); optic muscle atrophy; loss of bowel and bladder control; and, in males, impotence. Its effects on the nervous system may also produce irritability, poor memory, headache, depression, and delirium. Although some of these symptoms are temporary, irreversible CNS changes may have occurred before treatment.

❑ Cardiovascular: Increasingly fragile cell membranes induce widespread destruction of RBCs, resulting in low Hb levels. The impaired oxygen-carrying capacity of the blood secondary to lowered Hb leads to weakness, fatigue, and light-headedness. Compensatory increased cardiac output results in palpitations, wide pulse pressure, dyspnea, orthopnea, tachycardia, premature beats and, eventually, heart failure.

❑ Musculoskeletal: Scissors gait can also occur as a late sign of untreated anemia.

Diagnosis

A positive family history, typical ethnic heritage, and results of blood studies, bone marrow aspiration, gastric analysis, and the Schilling test establish the diagnosis. (See Tests for blood composition, production, and function, pages 1022 and 1023.) Laboratory screening must rule out other anemias with similar symptoms, such as folic acid deficiency anemia, because treatment differs. Diagnosis must also rule out vitamin B₁₂ deficiency resulting from malabsorption due to GI disorders, gastric surgery, radiation, or drug therapy.

Blood study results that suggest pernicious anemia include:

❑ decreased Hb levels (4 to 5 g/dl) and decreased RBC count

ELDER TIP Hb levels drop 1 to 2 g/ dl in elderly men, and HCT may decrease slightly in both men and women. These changes reflect decreased bone marrow and hematopoiesis and (in men) decreased androgen levels; they aren’t an indicator of pernicious anemia.

❑ increased mean corpuscular volume (greater than 120/µl); because larger-than-normal RBCs each contain increased amounts of Hb, mean corpuscular Hb concentration is also increased

❑ possible low white blood cell and platelet counts and large, malformed platelets

❑ serum vitamin B₁₂ assay levels less than 0.1 mcg/ml

❑ elevated serum lactate dehydrogenase levels.

Bone marrow aspiration reveals erythroid hyperplasia (crowded red bone marrow), with increased numbers of megaloblasts but few normally developing RBCs. Gastric analysis shows absence of free hydrochloric acid after histamine or pentagastrin injection.

Confirming diagnosis  The Schilling test is the definitive test for pernicious anemia. In this test, the patient receives a small oral dose (0.5 to 2 mcg) of radioactive vitamin B₁₂ after fasting for 12 hours. A larger dose (1 mg) of nonradioactive vitamin B₁₂ is given I.M. 2 hours later, as a parenteral flush, and the radioactivity of a 24-hour urine specimen is measured. About 7% of the radioactive B₁₂ dose is excreted in the first 24 hours; people with pernicious anemia excrete less than 3%. (In pernicious anemia, the vitamin remains unabsorbed and is passed in the stool.) When the Schilling test is repeated with IF added, the test shows normal excretion of vitamin B₁₂.

Important serologic findings may include IF antibodies and antiparietal cell antibodies.

Treatment

Early parenteral vitamin B₁₂ replacement can reverse pernicious anemia, minimize complications and, possibly, prevent permanent neurologic damage. An initial high dose of parenteral vitamin B₁₂ causes rapid RBC regeneration. Within 2 weeks, Hb levels should rise to normal, and the patient’s condition should markedly improve. Because rapid cell regeneration increases the patient’s iron and folate requirements, concomitant iron and folic acid replacement is necessary to prevent iron deficiency anemia.

After the patient’s condition improves, the vitamin B₁₂ dosage can be decreased to maintenance levels and given monthly. Because such injections must be continued for life, the patient should learn self-administration of vitamin B₁₂.

If anemia causes extreme fatigue, the patient may require bed rest until Hb levels rise. If Hb levels are dangerously low, he may need blood transfusions. Digoxin, a diuretic, and a low-sodium diet may be necessary for a patient with heart failure. Most important is the replacement of vitamin B₁₂ to control the condition that led to this failure. Antibiotics help combat accompanying infections.

Special considerations

Supportive measures minimize the risk of complications and speed recovery. Patient and family teaching can promote compliance with lifelong vitamin B₁₂ replacement.

❑ If the patient has severe anemia, plan activities, rest periods, and necessary diagnostic tests to conserve his energy. Monitor pulse rate often; tachycardia means his activities are too strenuous.

❑ To ensure accurate Schilling test results, make sure that all urine over a 24-hour period is collected and that the specimens are uncontaminated.

❑ Warn the patient to guard against infections and tell him to report signs of infection promptly, especially pulmonary and urinary tract infections, because the patient’s weakened condition may increase susceptibility.

❑ Provide a well-balanced diet, including foods high in vitamin B₁₂ (meat, liver, fish, eggs, and milk). Offer between-meal snacks and encourage the family to bring favorite foods from home.

❑ Because a sore mouth and tongue make eating painful, ask the dietitian to avoid giving the patient irritating foods. If these symptoms make talking difficult, supply a pad and pencil or some other aid to facilitate nonverbal communication; explain this problem to the family. Provide diluted mouthwash or, with severe conditions, swab the patient’s mouth with tap water or warm saline solution.

❑ Warn the patient with a sensory deficit not to use a heating pad, because it may cause burns.

❑ If the patient is incontinent, establish a regular bowel and bladder routine. After the patient is discharged, a home health care nurse should follow up on this schedule and make adjustments, as needed.

❑ If neurologic damage causes behavioral problems, assess mental and neurologic status often; if necessary, give tranquilizers, as ordered, and apply a jacket restraint at night.

❑ Stress that vitamin B₁₂ replacement isn’t a permanent cure and that these injections must be continued for life, even after symptoms subside.

❑ To prevent pernicious anemia, emphasize the importance of vitamin B₁₂ supplements for patients who have had extensive gastric resections or who follow strict vegetarian or vegan diets.

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Book Source Details

• Book Title: Professional Guide to Diseases (Eighth Edition)
• Author(s): Springhouse
• Year of Publication: 2005
• Copyright Details: Professional Guide to Diseases (Eighth Edition), Copyright © 2005 Lippincott Williams & Wilkins.

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More About This Book: Title: Professional Guide to Diseases (Eighth Edition) Authors: Springhouse Publisher: Lippincott Williams & Wilkins Copyright: 2005 ISBN: 1-58255-370-X

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