Anemi-recorded https://www.sPart II.pptx

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1. RBC DISORDERS Part II Dr . Rema Saad

2. Decreased red cell production Nutritional deficiencies Deficiencies affecting DNA synthesis B12 and folate deficiencies Deficiencies affecting hemoglobin synthesis Iron deficiency anemia Erythropoietin deficiency Renal failure, anemia of chronic disease Immune-mediated injury of progenitors Aplastic anemia, pure red cell aplasia 1/11/2021 2

3. 4. Inherited genetic defects Defects leading to stem cell depletion Fanconi anemia, telomerase defects Defects affecting erythroblast maturation Thalassemia syndromes 5. Inflammation-mediated iron sequestration Anemia of chronic disease 6. Primary hematopoietic neoplasms Acute leukemia, myelodysplasia , myeloproliferative disorders. 1/11/2021 3

4. 7. Space-occupying marrow lesions Metastatic neoplasms , granulomatous disease 8. Infections of red cell progenitors Parvovirus B19 infection 9. Unknown mechanisms Endocrine disorders, hepatocellular liver disease 1/11/2021 4

5. Megaloblastic Anemias The common theme among the various causes of megaloblastic anemia is an impairment of DNA synthesis that leads to ineffective hematopoiesis and distinctive morphologic changes, including abnormally large erythroid precursors and red cells. Causes : Vitamin B 12 deficiency. Folic acid deficiency. 1/11/2021 5

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8. Certain peripheral blood findings are shared by all megaloblastic anemias . The presence of red cells that are macrocytic and oval (macro- ovalocytes ) is highly characteristic. The MCHC is not elevated.* There is marked variation in the size ( anisocytosis ) and shape ( poikilocytosis ) of red cells. The reticulocyte count is low. Nucleated red cell progenitors occasionally appear in the circulating blood when anemia is severe. 1/11/2021 8

9. Neutrophils are also larger than normal ( macropolymorphonuclear ) and show nuclear hypersegmentation . 1/11/2021 9 A peripheral blood smear shows a hypersegmented neutrophil .

10. The marrow is usually markedly hypercellular as a result of increased hematopoietic precursors, which often completely replace the fatty marrow. Megaloblastic changes are detected at all stages of erythroid development . 1/11/2021 10

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12. The marrow hyperplasia is a response to increased levels of growth factors, such as erythropoietin. The anemia is further exacerbated by a mild degree of red cell hemolysis of uncertain etiology. 1/11/2021 12

13. Anemia of Vitamin B 12 deficiency: pernicious anemia Pernicious anemia is a specific form of megaloblastic anemia caused by an autoimmune gastritis that impairs the production of intrinsic factor, which is required for vitamin B12 uptake from the gut. 1/11/2021 13

14. Normal Vitamin B12 Metabolism. 1/11/2021 14

15. Biochemical Functions of Vitamin B12. 1/11/2021 15 Methyl cobalimin is one of the naturally occuring coenzymes forms of vitamin B 12 .

16. Pernicious anemia Incidence: occurs in all racial groups It is a disease of older adults; the median age at diagnosis is 60 years, and it is rare in people younger than 30. A genetic predisposition is strongly suspected, Pathogenesis : Pernicious anemia is believed to result from an autoimmune attack on the gastric mucosa. 1/11/2021 16

17. Histologically : there is a chronic atrophic gastritis marked by a loss of parietal cells, a prominent infiltrate of lymphocytes and plasma cells, and megaloblastic changes in mucosal cells similar to those found in erythroid precursors. 1/11/2021 17

18. Note: Vitamin B-12 deficiency is associated with disorders other than pernicious anemia. Achlohydria Loss of pepsin secretion Gastrectomy Loss of exocrine pancreatic function Ileal resection or ileal disease 1/11/2021 18

19. Morphology The blood and bone marrow changes , described earlier The stomach typically shows diffuse chronic gastritis fundic gland atrophy, affecting both chief cells and parietal cells, the latter being virtually absent. The glandular epithelium is replaced by mucus-secreting goblet cells that resemble those lining the large intestine, a form of metaplasia referred to as intestinalization . Atrophic glossitis . With time, the tongue may become shiny, glazed, and “beefy”. CNS lesions: demyelination of the dorsal and lateral spinal tracts 1/11/2021 19

20. Note : The gastric atrophy and metaplastic changes are due to autoimmunity and not vitamin B12 deficiency; hence, parenteral administration of vitamin B12 corrects the megaloblastic changes in the marrow and the epithelial cells of the alimentary tract, but gastric atrophy and achlorhydria persist. 1/11/2021 20

21. Note : The diagnosis is confirmed by an outpouring of reticulocytes and a rise in hematocrit levels beginning about 5 days after parenteral administration of vitamin B12. Persons with atrophy and metaplasia of the gastric mucosa associated with pernicious anemia have an increased risk of gastric carcinoma . Elevated homocysteine levels are a risk factor for atherosclerosis. 1/11/2021 21

22. Anemia of Folate Deficiency A deficiency of folic acid results in a megaloblastic anemia having the same pathologic features as that caused by vitamin B12 deficiency. 1/11/2021 22 folate does not prevent (and may even exacerbate) the neurologic deficits seen in vitamin B12 deficiency states . It is thus essential to exclude vitamin B12 deficiency in megaloblastic anemia before initiating therapy with folate.

23. Etiology The three major causes of folic acid deficiency are: decreased intake. 50 to 200 μg daily increased requirements. impaired utilization. 1/11/2021 23

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25. Iron Deficiency Anemia Deficiency of iron is the most common nutritional disorder in the world and results in a clinical signs and symptoms that are mostly related to inadequate hemoglobin synthesis. 1/11/2021 25

26. Iron in the body is recycled between the functional and storage pools 1/11/2021 26

27. Regulation of iron absorption Iron absorption is regulated by hepcidin , a small circulating peptide that is synthesized and released from the liver in response to increases in intrahepatic iron levels. 1/11/2021 27 divalent metal transporter Cytochrome B is ferrireductase

28. Etiology Iron deficiency can result from dietary lack. impaired absorption. increased requirement. chronic blood loss. 1/11/2021 28

29. To maintain a normal iron balance, about 1 mg of iron must be absorbed from the diet every day.* Heme iron is much more absorbable than inorganic iron, the absorption of which is influenced by other dietary contents.** enhanced by ascorbic acid, citric acid, amino acids, and sugars in the diet, and inhibited by tannates (found in tea), carbonates, oxalates, and phosphates. Dietary lack. 1/11/2021 29

30. Dietary iron inadequacy occurs in even privileged societies in the following groups: Dietary lack. Infants, who are at high risk due to the very small amounts of iron in milk. The impoverished, who can have suboptimal diets for socioeconomic reasons at any age. Older adults, who often have restricted diets with little meat because of limited income or poor dentition. Teenagers who subsist on “junk” food. 1/11/2021 30

31. Impaired absorption is found in fat malabsorption ( steatorrhea ), and chronic diarrhea. Gastrectomy impairs iron absorption by decreasing the acidity of the proximal duodenum (which enhances uptake), and also by increasing the speed with which gut contents pass through the duodenum. Specific items in the diet can also affect absorption. 1/11/2021 31 impaired absorption.

32. Increased requirement is an important cause of iron deficiency in : growing infants, children, and adolescents, as premenopausal women, particularly during pregnancy. Economically deprived women having multiple, closely spaced pregnancies are at exceptionally high risk. 1/11/2021 32 increased requirement.

33. Is the most common cause of iron deficiency in the Western world. External hemorrhage or bleeding into the gastrointestinal, urinary, or genital tracts depletes iron reserves. 1/11/2021 33 chronic blood loss. Iron deficiency in adult men and postmenopausal women in the Western world must be attributed to gastrointestinal blood loss until proven otherwise.

34. Iron absorption

35. Pathogenesis. Whatever its basis, iron deficiency produces a hypochromic microcytic anemia. 1/11/2021 35 At the outset of negative iron balance, reserves in the form of ferritin and hemosiderin may be adequate to maintain normal hemoglobin and hematocrit levels as well as normal serum iron and transferrin saturation.

36. Progressive depletion of these reserves first lowers serum iron and transferrin saturation levels without producing anemia. In this early stage there is increased erythroid activity in the bone marrow. 1/11/2021 36 Anemia appears only when iron stores are completely depleted and is accompanied by lower than normal serum iron, ferritin , and transferrin saturation levels.

37. MORPHOLOGY The bone marrow reveals: a mild to moderate increase in erythroid progenitors. A diagnostically significant finding is the disappearance of stainable iron from macrophages in the bone marrow, which is best assessed by performing Prussian blue stains on smears of aspirated marrow. 1/11/2021 37

38. MORPHOLOGY In peripheral blood smears: the red cells are small ( microcytic ) and pale ( hypochromic ). In established iron deficiency the zone of pallor is enlarged; hemoglobin may be seen only in a narrow peripheral Rim. Poikilocytosis in the form of small, elongated red cells (pencil cells) is also characteristically seen. 1/11/2021 38

39. 1/11/2021 39 Normochromic: Normal red cells with sufficient hemoglobin have a zone of central pallor measuring about one third of the cell diameter. Hypochromic