Anemia

1. Anemia Mike Clark, M.D.

2. Anemia is a decrease in the normal number of red blood cells (RBCs) or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin deficiency. Because anemia has multiple causes (etiologies) a work-up must be performed to identify the specific cause or in some cases causes.

3. Symptoms Most commonly, people with anemia report non-specific symptoms of a feeling of weakness, or fatigue, general malaise and sometimes poor concentration. They may also report shortness of breath, dyspnea, on exertion. In very severe anemia, the body may compensate for the lack of oxygen carrying capability of the blood by increasing cardiac output. The patient may have symptoms related to this, such as palpitations, angina (if preexisting heart disease is present), intermittent claudication of the legs, and symptoms of heart failure

4. Signs • On examination, the signs exhibited may include pallor (pale skin, mucosal linings and nail beds) but this is not a reliable sign. There may be signs of specific causes of anemia, e.g., koilonychia (in iron deficiency), jaundice (when anemia results from abnormal break down of red blood cells — in hemolytic anemia), bone deformities (found in thalassemia major) or leg ulcers (seen in sickle cell disease).

6. History and Physical • As a result of the non-specific signs and symptoms a history and physical examination is performed.

7. Two main causes of anemia • Decreased Production of red blood cells and/or hemoglobin • Increased destruction of red blood cells and/or hemoglobin • Main test to distinguish the difference is the reticulocyte count. Normal count is .5 – 2% • Generally a low normal to low reticulocyte count is caused by decreased production and high one is caused by increased destruction

8. Decreased Production Causes • Reduction in red blood cells or subnormal level of hemoglobin • Inadequate production of red cells • Insufficient raw materials • Iron deficiency • Vitamin B12 deficiency • Folic acid deficiency • Inability to deliver adequate red cells into circulation due to marrow damage or destruction (aplastic anemia), replacement of marrow by foreign or abnormal cells

9. Increased Destruction Causes • Excessive loss of red cells • External blood loss (hemorrhage) • Shortened survival of red cells in circulation • Defective red cells: hereditary hemolytic anemia • Accelerated destruction of cells from antibodies to red blood cell or by mechanical trauma to circulating red cells

11. Diagnostic Evaluation of Anemia • 1. History and physical examination • 2. Complete blood count: to assess degree of anemia, leukopenia, and thrombocytopenia • 3. Blood smear: determine if normocytic, macrocytic, or hypochromic microcytic • 4. Reticulocyte count: assess rate of production of new red cells • 5. Lab tests: determine iron, B12, folic acid • 6. Bone marrow study: study characteristic abnormalities in marrow cells • 7. Evaluation of blood loss from gastrointestinal tract to localize site of bleeding

12. CBC indices regarding red blood cells • Red Blood Cell Count - 4.8 – 5.4 million per microliter • Hematocrit ( 30 – 60) generally 45% to 52% for men and 37% to 48% for women • Hemoglobin ( 13 to 18 grams per deciliter for men and 12 to 16 for women) • MCV (Mean Corpuscular Volume) - 80 to 100 • MCH (Mean Corpuscular Hemoglobin) –this is the average amount of Hgb. in a the typical red blood cell. 27 to 32 picograms • MCHC (Mean Corpuscular Hemoglobin Conc.) - the average concentration of hemoglobin in a given volume of red cells (32 – 36%) • RDW – (Red Cell Distribution Width) – a measurement of the variability of red cell size and shape. Higher numbers indicate greater variation in size 11 - 15

13. Peripheral Smear • Look at size – 6 – 9 micromillimeters • Too small – microcytic • Too big – macrocytic • Normal size – normocytic • Look at color • Too pale – hypochromic • Too dark – hyperchromic • Normal color - normochromic

14. Anemia: Morphologic Classification • Classification based on red cell appearance suggests the etiology of the anemia: • Normocytic anemia: normal size and appearance • Macrocytic anemia: cells larger than normal • Folic acid deficiency • Vitamin B12 deficiency • Microcytic anemia: cells smaller than normal

15. Anemia: Morphologic Classification • Hypochromic anemia: reduced hemoglobin content • Hypochromic microcytic anemia: smaller than normal and reduced hemoglobin content

16. Increased Destruction (Peripheral) • Too extensive destruction after cells have been formed and released from bone marrow • Generally find a high reticulocyte count – because more and more immature red blood cells are being released from bone marrow to compensate for the shortage in the peripheral circulation

17. Possible Causes of Increased Destruction • Acquired hemolytic anemia • Normal red cells but unable to survive due to a “hostile environment” • Attacked and destroyed by antibodies • Destruction of red cells by mechanical trauma • Passing through enlarged spleen (splenomegaly) • In contact with some part of artificial heart valve

18. Possible Causes of Increased Destruction Hemolytic Anemia (Genetic) • Hereditary hemolytic anemia • Genetic abnormality prevent normal survival • 1. Abnormal shape: hereditary spherocytosis • 2. Abnormal hemoglobin: hemoglobin S (sickle hemoglobin); hemoglobin C; both found predominantly in persons of African descent • 3. Defective hemoglobin synthesis: thalassemia minor and major; globin chains are normal but synthesis is defective (Greek and Italian ancestry) • 4. Enzyme defects: glucose-6-phosphatase dehydrogenase deficiency predisposes to episodes of acute hemolysis

19. Distortion of red cells containing sickle hemoglobin when incubated under reduced oxygen tension.

20. Distortion of red calls containing sickle hemoglobin when incubated under reduced oxygen tension. Higher magnification view.

22. Decreased Production • Something is causing red blood cells not to be produced fast enough • Generally the reticulocyte count is low or low normal. The reason is that if production is bad –reticulocytes (immature red blood cells) also cannot be produced adequately.

23. Classification of anemia based on the “bone marrow factory” concept

24. Iron-Deficiency Anemia • Characteristic laboratory profile • Low serum ferritin and serum iron • Higher than normal serum iron-binding protein • Lower than normal percent iron saturation • Treatment • Primary focus: learn cause of anemia • Direct treatment towards cause than symptoms • Administer supplementary iron • Examples • Infant with a history of poor diet • Adults: common cause is chronic blood loss from GIT (bleeding ulcer or ulcerated colon carcinoma) • Women: excessive menstrual blood loss • Too-frequent blood donations

25. Normal red cells

26. Cells of hypochromic microcytic anemia

27. Vitamin B12 Deficiency Anemia • Vitamin B12: meat, liver, and foods rich in animal protein • Folic acid: green leafy vegetables and animal protein foods • Both required for normal hematopoiesis and normal maturation of many other types of cells • Vitamin B12: for structural and functional integrity of nervous system; deficiency may lead to neurologic disturbances

28. Vitamin B12 Deficiency Anemia • Absence or deficiency of vitamin B12 or folic acid • Abnormal red cell maturation or megaloblastic erythropoiesis with formation of large cells called megaloblasts • Mature red cells formed are larger than normal or macrocytes; corresponding anemia is called macrocytic anemia • Abnormal development of white cell precursors and megakaryocytes: leukopenia, thrombocytopenia

29. Most vitamin B12 deficiency symptoms are actually folate deficiency symptoms, since they include all the effects of pernicious anemia and megaloblastosis, which are due to poor synthesis of DNA when the body does not have a proper supply of folic acid for the production of thymine. When sufficient folic acid is available, all known B12 related deficiency syndromes normalize, save those narrowly connected with the vitamin B12-dependent enzymes

30. The total amount of vitamin B12 stored in body is about 2–5 mg in adults. Around 50% of this is stored in the liver. Approximately 0.1% of this is lost per day by secretions into the gut as not all these secretions are reabsorbed. Bile is the main form of B12 excretion, however, most of the B12 that is secreted in the bile is recycled via enterohepatic circulation

31. Macrocytic Cells

32. Pernicious Anemia • Lack of intrinsic factor results in macrocytic anemia • Vitamin B12 in food combines with intrinsic factor in gastric juice • Vitamin B12 intrinsic factor complex absorbed in ileum • Causes • Gastric mucosal atrophy; also causes lack of secretion of acid and digestive enzymes • Gastric resection and bypass: vitamin B12 not absorbed • Distal bowel resection or disease: impaired absorption of vitamin B12 intrinsic factor complex • May develop among middle-aged and elderly • Associated with autoantibodies against gastric mucosal cells and intrinsic factor

33. Cardia Fundus Esophagus Muscularis externa Serosa • Longitudinal layer • Circular layer Body • Oblique layer Lumen Lesser curvature Rugae of mucosa Greater curvature Pyloric canal Pyloric antrum Duodenum Pyloric sphincter (valve) at pylorus (a) Figure 23.14a

34. Gastric pits Surface epithelium (mucous cells) Gastric pit Mucous neck cells Parietal cell Chief cell Gastric gland Enteroendocrine cell (b) Enlarged view of gastric pits and gastric glands Figure 23.15b

35. Folic Acid Deficiency Anemia • Relatively common • The body has very limited stores, which rapidly become depleted if not replenished continually • Pathogenesis • Inadequate diet: encountered frequently in chronic alcoholics • Poor absorption caused by intestinal disease • Occasionally occurs in pregnancy with increased demand for folic acid

36. Polycythemia • Secondary polycythemia • Reduced arterial O2 saturation leads to compensatory increase in red blood cells (increased erythropoietin production) • Emphysema, pulmonary fibrosis, congenital heart disease; increased erythropoietin production by renal tumor • Primary/Polycythemia vera • Manifestation of diffuse marrow hyperplasia of unknown etiology • Overproduction of red cells, white cells, and platelets • Some cases evolve into granulocytic leukemia

37. Polycythemia • Complications • Clot formation due to increased blood viscosity and platelet count • Treatment • Primary polycythemia: treated by drugs that suppress marrow function • Secondary polycythemia: periodic removal of excess blood