Atlas of pathophysiology, 2 Edition

Part II - Disorders

Hematologic Disorders

Anemia

Anemia causes lower than normal levels of erythrocytes in the blood. There are several types of anemia, including aplastic, iron deficiency, and pernicious. Iron deficiency anemia affects 10% to 30% of adults in the United States.

Causes

Aplastic anemia

·   Congenital

·   Autoimmune reactions or other severe disease (hepatitis)

·   Radiation (about half of such anemias)

·   Drugs (antibiotics, anticonvulsants)

·   Toxic agents (benzene)

Iron deficiency anemia

·   Inadequate dietary intake of iron (less than 1 to 2 mg/day)

·   Iron malabsorption, as in chronic diarrhea, partial or total gastrectomy, or malabsorption syndromes, such as celiac disease and pernicious anemia

·   Blood loss

·   Pregnancy, which diverts maternal iron to fetus

·   Intravascular hemolysis-induced hemoglobinuria or paroxysmal nocturnal hemoglobinuria

·   Mechanical trauma by prosthetic heart valve or vena cava filters

Pernicious anemia

·   Genetic predisposition

·   Immunologically related disorder, such as thyroiditis, myxedema, Graves' disease

·   Partial gastrectomy

·   Age over 60 years

Pathophysiology

Aplastic anemia usually develops when damaged or destroyed stem cells inhibit blood cell production. Less commonly, damage to bone marrow microvasculature creates an unfavorable environment for cell growth and maturation.

Iron deficiency anemia occurs when the supply of iron is inadequate for optimal formation of red blood cells (RBCs); the result is microcytic cells with pale color (hypochromic) on staining. Body stores of iron, including plasma iron, become depleted, and the concentration of serum transferrin, which binds with and transports iron, decreases. Insufficient iron stores lead to a depleted RBC mass with low hemoglobin (Hb) concentration and impaired oxygen-carrying capacity.

Decreased production of hydrochloric acid in the stomach and a deficiency of intrinsic factor characterize pernicious anemia. The resulting vitamin B12 deficiency inhibits cell growth, leading to the production of scant, deformed, macrocytic RBCs having poor oxygen-carrying capacity. It also causes neurologic damage by impairing myelin formation.

Signs and symptoms

Aplastic anemia

·   Progressive weakness, fatigue, and altered level of consciousness

·   Ecchymosis, pallor, petechiae, and hemorrhage from the mucous membranes or into the retina

·   Fever, oral and rectal ulcers, and sore throat

·   Bibasilar crackles and tachycardia

Iron deficiency anemia

·   Tachycardia

·   Spoon-shaped, brittle nails

·   Glottitis

Pernicious anemia

·   Weakness, numbness, and tingling of extremities

·   Gingival bleeding and tongue inflammation

·   Disturbed position sense, lack of coordination, impaired fine finger movement, and altered vision, taste, and hearing

·   Irritability, poor memory, headache, depression, delirium, and ataxia; changes may have occurred before treatment

·   Palpitations, tachycardia, and systolic murmur

Diagnostic test results

Aplastic anemia

·   Laboratory studies show 1 million/mm3 or fewer RBCs of normal color and size with a very low absolute reticulocyte count, elevated serum iron level, normal or slightly reduced total iron-binding capacity, and decreased platelet, neutrophil, and lymphocyte counts.

·   Bone marrow biopsy may show severely hypocellular or aplastic marrow and depression of RBCs and precursors.

Iron deficiency anemia

·   Laboratory analysis reveals low hematocrit, low Hb, low serum ferritin and serum iron with high binding capacity, low RBC count with microcytic and hypochromic cells, decreased mean corpuscular Hb, and depleted or absent iron stores.

·   Bone marrow studies show hyperplasia of precursor cells.

Pernicious anemia

·   Schilling test shows excretion of radiolabeled vitamin B12.

·   Laboratory analysis shows Hb level 4 to 5 g/dl, low RBC count, mean corpuscular volume greater than 120 mm3, and serum vitamin B12 less than 0.1 mcg/ml.

·   Bone marrow aspiration shows erythroid hyperplasia with increased megaloblasts but few normally developing RBCs.

·   Gastric analysis shows the absence of free hydrochloric acid after histamine or pentagastrin injection.

·   Antibody testing reveals intrinsic factor antibodies and antiparietal cell antibodies.

Treatment

Aplastic anemia

·   RBC or platelet transfusion; experimental histocompatibility locus antigen-matched leukocyte transfusions

·   Bone marrow transplantation

·   Measures to prevent infection and antibiotics

·   Respiratory support with oxygen

·   Corticosteroids, marrow-stimulating agents, immunosuppressive agents, and colony-stimulating factors

Iron deficiency anemia

·   Oral iron or iron and ascorbic acid combination

·   Parenteral iron

·   Iron-rich foods

Pernicious anemia

·   Early parenteral vitamin B12 replacement

·   After initial response, lifelong monthly dose of vitamin B12

·   Blood transfusions

·   Digoxin, diuretic, and low-sodium diet (for heart failure)

P.241

PERIPHERAL BLOOD SMEAR IN APLASTIC ANEMIA

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PERIPHERAL BLOOD SMEAR IN PERNICIOUS ANEMIA

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PERIPHERAL BLOOD SMEAR IN IRON DEFICIENCY ANEMIA

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