Anemia Mike Clark M D Anemia is a

Anemia Mike Clark, M. D.

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.

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

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).

Pallor koilonychia

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

Lab Tests

CBC Values • If you wish to understand the meaning of each value on a CBC go to my MS-Word Document: CBC Explanation of Values

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

Anemia Normal to increased reticulocyte count Increased Peripheral Destruction Hemorrhage Splenomegaly hemolytic The red blood cells are produced and released from the bone marrow correctly, but they are destroyed for some reason outside the bone marrow. Normal to decreased reticulocyte count Decreased Production Iron Deficiency Vitamin B 12 Deficiency The bone marrow is not producing red blood cells effectively and/or not releasing them sufficiently.

Anemia Normal to increased reticulocyte count Increased Peripheral Destruction Hemorrhage Splenomegaly hemolytic Size and rbc color OK Normocytic -Normochromic Normal to decreased reticulocyte count Decreased Production Bone marrow problem Stem Cell Problem Hormone problem Iron Deficiency Vitamin B 12 Deficiency

Decreased Production Causes • Reduction in red blood cells or subnormal level of hemoglobin • Inadequate production of red cells • Insufficient raw materials – Iron deficiency – Vitamin B 12 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

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

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, B 12, 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

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

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

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 B 12 deficiency – Microcytic anemia: cells smaller than normal

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

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

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

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

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

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

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.

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

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

Normal red cells

Cells of hypochromic microcytic anemia

Vitamin B 12 Deficiency Anemia • Vitamin B 12: 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 B 12: for structural and functional integrity of nervous system; deficiency may lead to neurologic disturbances

Vitamin B 12 Deficiency Anemia • Absence or deficiency of vitamin B 12 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

Most vitamin B 12 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 B 12 related deficiency syndromes normalize, save those narrowly connected with the vitamin B 12 dependent enzymes

The total amount of vitamin B 12 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 B 12 excretion, however, most of the B 12 that is secreted in the bile is recycled via enterohepatic circulation

Macrocytic Cells

Pernicious Anemia • Lack of intrinsic factor results in macrocytic anemia – Vitamin B 12 in food combines with intrinsic factor in gastric juice – Vitamin B 12 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 B 12 not absorbed – Distal bowel resection or disease: impaired absorption of vitamin B 12 intrinsic factor complex – May develop among middle-aged and elderly – Associated with autoantibodies against gastric mucosal cells and intrinsic factor

Cardia Esophagus Muscularis externa • Longitudinal layer • Circular layer • Oblique layer Lesser curvature Fundus Serosa Body Lumen Rugae of mucosa Greater curvature Duodenum (a) Pyloric canal antrum Pyloric sphincter (valve) at pylorus Figure 23. 14 a

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. 15 b

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

Polycythemia • Secondary polycythemia – Reduced arterial O 2 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

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