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 – 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

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. (b) Enlarged view of gastric pits and gastric glands
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 Primary/Polycythemia vera
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 Treatment
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