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Bone marrow Red Yellow Bone Fat Reticulin Haematopoiesis – red, white, platelets lymphoid.

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Presentation on theme: "Bone marrow Red Yellow Bone Fat Reticulin Haematopoiesis – red, white, platelets lymphoid."— Presentation transcript:

1 Bone marrow Red Yellow Bone Fat Reticulin Haematopoiesis – red, white, platelets lymphoid

2 Normal red cells Central pale area

3 Red cells MenWomen Hemoglobin (g/l) Hematocrit (%) Red cell count (10 12 /l) Reticulocyte count (%) Mean cell volume (fl)80-95 Mean corpuscular hemoglobin (pg)27-33 Mean corpuscular hemoglobin concentration (gm/dL) 33-37

4 Red cells pathological conditions: I.decrease in the circulating red cell mass (poss. with structural abnormalities) very common - anaemia II. increase in the circulating red cell mass less common polycythemia =erythrocytosis=polyglobuly

5 Polycythemia =increased concentration of red cells RELATIVE - decreased plasma volume dehydration, stress ABSOLUTE primary – neoplastic= polycythemia vera = myeloproliferative neoplasm secondary - increased erythropoietin stimulation  Appropriate  reactive – low levels of oxygen in the PB (heart disease, high altitude)  Inappropropriate

6 Red cells Normal: uniform in size and shape Pathologic: variation in size, shape, inclusions Variation size - anisocytosis Shape – poikilocytosis

7 Red cells - functions Deliver oxygen to the tissues Anemia - reduction of the total number of red cells amount of hemoglobin circulating red cell mass

8 Consequences of anemia - symptoms ???????????

9 Dg. of anemia - history Age of onset Duration of illness Prior therapy of anemia Suddennes or severity of anemia Chronic blood loss Hemolytic episodes Toxic exposures Dietary history Family history, racial background Underlying diseases

10 Anemia – consequences, symptoms Fatigue, syncope, dyspnea Impairment of organ function due to hypoxia Pallor, postural hypotension )decreased blood volume) Heart murmurs, heart failure. Increased cardiac output

11 Anemia Not a diagnosis per se Look for an underlying problem History, physical examination

12 Anaemia decrease in the total circulating red cell mass (hematocrit, hemoglobin concentration) Classification: A. underlying mechanism blood loss increased destruction decreased production B. morphology of erythrocytes size (micro-, macro-, normocytic) shape (spherocytosis, stomato-,...) color (degree of hemoglobinization: normo- hypo-, hyperchromic) MAYCOMBINEMAYCOMBINE

13 Acute Hypovolemia – shock Anemia – normocytic normochromic Shift of water – hemodilution –↓ hematocrite Compensatory increase of red cell production Reticulocytes Chronic → loss of iron→ iron deficiency hypochromic sideropenic anemia Blood loss acute or chronic internal or external

14 Iron deficiency anemia mechanism: blood loss, decreased production body iron = functional + storage F - 2g, M - 6g inadequate intake for metabolic demands Lack in diet or low absorption most common nutritional disorder in the world 2. Increased requirement (children, pregn., lact) !!!3. Chronic blood loss!!! - GIT, GYN most important cause of iron deficiency in the Western world

15 Hypochromic microcytic sideropenic anemia Scattered fully hemoglobinized cells - blood transfusion Small hemoglobinization (narrow Hb rim -periphery) Small red cells Iron deficiency

16 PB: ery pale + small BM: erythroid hyperplasia, loss of iron alopecia, koilonychia, atrophy of tongue, gastric mucosa Plummer-Vinson (Kelly-Patterson) syndrome: siderop.an., atrophic glossitis, esophageal webs

17 Iron deficiency anaemia Pallor conjunctiva skin pale palmar creases

18 Iron deficiency anaemia koilonychia nails concave (or flat), ridged, brittle

19 Iron deficiency anaemia angular cheilosis fissuring and ulceration; pallor

20 Iron deficiency anaemia flattening and loss of papillae bald, fissured tongue

21 Causes of hypochromic anemia 1.Disorders of iron metabolism 2.Disorders of heme synthesis 3.Disorders of globin synthesis (thalassemia) Ad 1. Iron deficiency Blood loss Poor intake - growth, pregnancy, lactation Malabsorption Chronic infections or inflammatory states neoplasia

22 Anaemia decrease in the total circulating red cell mass (hematocrit, hemoglobin concentration) Classification: A. underlying mechanism blood loss → increased destruction decreased production

23 Increased destruction =lysis of red cells=hemolysis intravascular – rare - mechanical injury – artificial valves or microthrombi, exogenous toxic agents, complement fixation (transfusion of mismatched blood) extravascular - more common, when red cells considered foreign or less deformable Hemolytic anemia Abnormality:  intracorpuscular or extracorpuscular  hereditary (intra) or acquired (extra)

24 Hemolytic anemia premature destruction of red cells accumulation of the products of the hemoglobin catabolism BM – increased erythropoiesis, extreme: extramedullary hematopoiesis PB: reticulocytosis high bilirubin –gallstones; jaundice, blr in urine chronic duration: hemosiderosis Main clinical symptoms anemia, splenomegaly, jaundice; gallstones

25 Haemolytic anaemia splenomegaly and jaundice

26 Haemolytic anaemia jaundice normal

27 Increased destruction of ery=hemolysis I. Intrinsic (intracorpuscular) causes A. hereditary membrane – cytoskeleton, lipid synthesis enzymes – deficiencies - G6PD, glutathione synthetase, pyruvate kinase hemoglobin - deficient synthesis of globin, structurally abnormal Hb B. acquired membrane defect: paroxysmal nocturnal hemoglobinuria II. Extrinsic (extracorpuscular) causes antibodies, trauma, infection, chemical injury sequestration

28 Examples of hemolytic anemia Membrane defects – Proteins underlying the red cell membrane Shape, stability, flexibility

29 Hereditary spherocytosis (peripheral smear) anisocytosis and several dark-appearing spherocytes with no central pallor. Howell-Jolly bodies (small dark nuclear remnants)

30 Hereditary spherocytosis AD (AR, sporadic);most common her. hemol. A. Membrane defect – cytoskeleton – protein spectrin (and ankyrin) deficiency Round erythrocyte= spherocyte, less deformable Vulnerable to spleen sequestration and destruction Main clinical symptoms anemia, splenomegaly, jaundice; gallstones Chronic hemolytic anemia (mild to normal) Acute anemic episodes: aplastic crisis (parvovirus) hemolytic crisis

31 Table Adult Reference Ranges for Red Blood Cells*Table Adult Reference Ranges for Red Blood Cells* A red cell squeezing from the red pulp cordsinto the sinus lumen. Note the degree of deformability required for red cells to pass through the wall of the sinus. Splenic sinus

32 Mutations weakening interactions involving α-spectrin, β-spectrin, ankyrin, band 4.2, or band 3 cause the normal biconcave red cell to lose membrane fragments and become spherical spherocytic cells: less deformable than normal, become trapped in the splenic cords, phagocytosed by macrophages. Red cell membrane cytoskeleton Alterations leading to spherocytosis and hemolysis

33 Pathophysiology of hereditary spherocytosis

34 Haemolytic anaemia: reticulocytes precip. RNA

35 Hereditary elliptocytosis Usually mild, rarely severe

36 Hemolytic anemia Intracorpuscular Enzyme deficiencies

37 G6PD deficiency enzymes protecting the red cell against the oxidative stress G6PD deficiency → loss of protection → oxidant injury infections, drugs, beans (favism) → hemolysis; otherwise normal morphologic changes of chronic HA rarely present hundreds of genetic forms of G6PD common pathologic alleles: G6PDA -, G6PD Mediterranean X-linked→ males homozygous, women heterozygous Mediterranean, Middle East, Africa Protection against malaria

38 G6PD deficiency Clinical and laboratory findings Episode of acute hemolytic anemia in anotherwise healthy person; neonatal jaundice following oxid. injury – drug (antimal. – primaquine,; sulfoamides, nitrofurantoin, nalidixic acid; TNT,, infections, food Variable severity

39 Enzyme deficiency: G6PD deficiency effects of oxidant drug exposure (PB) Red cells with precipitates of denatured globin (Heinz bodies) splenic macrophages pluck out these inclusions → "bite cells"

40 Increased destruction of ery=hemolysis I. Intrinsic causes A. hereditary membrane – cytoskeleton, lipid synthesis enzymes – deficiencies - G6PD, glutathione synthetase, pyruvate kinase →hemoglobin – abnormal quantity (deficient synthesis of globin) quality (structurally abnormal Hb)

41 Shape: sickle Hereditary hemoglobinopathy Structurally abnormal hemoglobin HbS abnormal physiochemical properties B-globin – 6 th position, Molecular defect: point mutation valine for glutamic acid Sickle cell anemia (PB)

42 Sickle cell anemia Hemolysis, microvascular occlusion

43 Sickle cell anemia Oxyg. HbS: liquid Deoxyg.:viscous gel →fibers HbS - aggregation and polymerization Sickle shape; Initially: reversible (with oxygenation) Repeated: irreversible sickling Membrane damage

44 Rate and degree of sickling 1. Amount of HbS Heterozygotes: HbS and HbA – only sickle cell trait (sickling when marked hypoxia) Homozygotes: severe anemia 2. Hemoglobin concentration the higher, the worse 3. Fall in pH → deoxygenation

45 Sickle cell anemia - clinical manifestation 1.chronic hemolytic anemia (ery survival 20 days) chronic hyperbilirubinemia, Hbemia, jaundice, gallstones aplastic crisis 2. occlusion of small vessels → thrombosis, ischemia, necrosis painful crises 3. splenomegaly 4. increased susceptibility to infections 5. activation of the bone marrow, extramedullary haematopoiesis

46 Diagnosis Clinical, laboratory – blood smear HbS - electrophoresis Clinical course variable Therapy symptomatic

47 Thalassemia Deficient synthesis of globin chains Globin chain absent or amount reduced β - major, minor (more common), intermedia β +,0 Homo/heterozygous α +,0

48 Scleral jaundice Haemolytic autoimmune anaemia

49 Pathogenesis of β-thalassemia major aggregates of unpaired α-globin chains not visible Blood transfusions correct the anemia reduce the stimulus for marrow expansion, but add to systemic iron overload

50 Thalassemia major: gallbladder - bilirubin gallstones

51 Immunohemolytic anemia Antibodies Coombs test

52 Raynaud phenomenon autoimmnune haemolytic anaemia

53 Erythroblastosis fetalis

54 Decreased production of red cells Deficiency of vital substrates disorders of proliferation and differentiation  stem cells  erythroblasts Impaired:  DNA synthesis – B 12, folic acid – megaloblastic  hemoglobin synthesis - heme (lack of iron) - globin  Others: anemia of chron. dis., AA, PRCA

55 Megaloblastic anemia impaired DNA synthesis characteristic morphologic changes blood (macrocytes), bone marrow (megaloblasts) Deficiency of vit. B 12 Folic acid

56 Megaloblastic anaemia

57 Vitamin B 12 absorption

58 Deficiency of vit. B Decreased intake – diet, vegetarianism 2. Impaired absorption Intrinsic factor deficiency – pernicious anemia, gastrectomy Malabsorption Intestinal dis., resection of ileum Parasitic uptake, bacterial overgrowth 3. Increased requirement pregnancy, hyperthyroidism, disseminated cancer

59 Vit. B 12 deficiency BM and blood, CNS, (pernicious: GIT) GIT: beefy tongue – atrophic glossitis CNS – spinal cord - myelin degenaration laterodorsal tracts – balance, motoric, sensitive Pernicious: stomach: chronic gastritis, intestinal metaplasia, higher risk of carcinoma

60 Pernicious anemia Older people Autoimmune Ab Poss. with autoimmune thyroiditis, adrenalitis

61 Megaloblastic anaemia Acute leukaemia Diffferential diagnosis

62 Megaloblastic anaemia hypersegmented neutrophils (macropolycyte)

63 Megaloblastic anaemia - pernicious lemon-yellow appearance pallor (anaemia) + jaundice (ineffective erythropoiesis)

64 Pernicious anaemia (38 ys.) premature greying, blue eyes, vitiligo

65 Beefy tongue atrophic glossitis (Hunter) vit. B12 deficiency

66 Pernicious anaemia Dorsolateral spinal cord demyelination

67 Folate deficiency Decreased intake Increased requirements Impaired use Relative deficiency Megaloblastic anemia; no neurological symptoms Cheilosis, glossitis, dermatitis

68 Anemia of chronic disease *Infections *immunologic *neoplasms Mechanism: defect in reutilization of iron (transfer, cytokines) ! abundant storage iron Anemia: normo, normo or hypo, micro

69 Aplastic anemia Failure or suppression of myeloid stem cell PANCYTOPENIA primary OR secondary - drugs, chemicals infections irradiation inherited – Fanconi Or cause unknown… BM: hypocellular, PB: pancytopenia, symptoms spleen normal Special subgroup: pure red cell anemia

70 Aplastic anemia Markedly hypocellular marrow contains mainly fat cells.


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