Hematopoietic System

1. Hematopoietic System Dr. Mohamad Nidal Khabaz Assistant Professor of Pathology, Pathology Department, Faculty of Medicine, Jordan University of Science and Technology

2. Hematopoiesis • All mature blood cells originate from pluri-potent stem cells in the bone marrow. • Pluripotent stem cells have high level of proliferation and self reproduction. They may change through several steps of development to different cell types. • Maturation of cells is going through several intermediate steps. • Usually only mature cells can reach blood

3. Normal bone marrow. Note the presence of megakaryocytes, erythroid islands, and granulocytic precursors.

4. Hematopoiesis • Capacity to differentiate is increasing and capacity to divide and sel-production is decreasing during maturation. Mature blood cells are not able to divide. • The proliferation, differentiation, and functional abilities of the various blood cells are controlled by cytokines (produced by lymphocytes and stromal cells of the bone marrow). • Hematopoiesis must and is very carefully regulated to hold stable number of cells in the blood.

5. Hematopoiesis • Cytokines (colony stimulating factors) stimulate hematopoietic cell colonies from bone marrow precursors: • EPO (Erythropoietin) • TPO (Thrombopoietin) • G-CSF (Granulocyte colony stimulating factor) • GM-CSF (Granulocyte-monocyte colony stimulating factor) • Increase peripheral stem cells for transplantation • Accelerate cell proliferation after bone marrow engraftment

6. HEMATOPOIETIC FACTORS n, neutrophils; m, monocytes; e, eosinophils; b, basophils; meg, megakaryocytes; rbc, red blood cells IL – interleukin , CSF – colony stimulating factor

8. Blood Cells

10. BLOOD

11. Physical Characteristics and Volume of the Blood • Blood is a sticky, thick fluid with a metallic taste • Color varies from scarlet (oxygen-rich) to dark red (oxygen-poor) • The pH of blood is 7.35–7.45 • Temperature is 38C, slightly higher than “normal” body temperature • Blood accounts for approximately 8% of body weight • Average volume of blood is 5–6 L for males, and 4–5 L for females.

12. Functions of the Blood • Carries oxygen from lungs to all body cells & removes carbon dioxide from the cells. • Carries waste products of cell activity to kidneys to be removed from the body. • Transports nutrients from digestive system to body cells.

13. Functions of the Blood • Transports hormones from endocrine glands to target organs • Blood cells help fight infection and heal wounds (white blood cells & platelets). • Blood maintains appropriate body temperature by absorbing and distributing heat.

14. Composition of Blood • Blood separates into two main parts: • Plasma accounts for 55% • Formedelements (Blood cells) 45% of blood volume, Produced in red bone marrow. They are three kinds: • Red = erythrocytes • White = leukocytes • Platelets = thrombocytes

16. Function of the Plasma • Carry the cells that transport gases • Aid in body defenses • Prevent blood loss

17. Plasma Proteins • Albumin • Comprise approximately 54% of the plasma proteins • Contribute to plasma osmotic pressure and the maintenance of blood volume • Serve as a carrier for certain substances • Globulins • Comprise approximately 38% of plasma proteins

18. Plasma Proteins (cont.) • Alpha globulins transport bilirubin and steroids • Beta globulins transport iron and copper • Gamma globulins constitute the antibodies of the immune system. • Fibrinogen • Make up approximately 7% of the plasma proteins • Is converted to fibrin in the clotting process

19. Blood cells • Red blood cells • Platelets • Leukocytes are 5 types of white blood cells protect against disease: • Basophils. • Eosinophils. • Neutrophils. • Lymphocytes. • Monocytes

22. Red Blood Cells (RBCs)

23. Erythrocytes: Red Blood Cells • Normally there are 4 to 6 million RBCs per mm3 of whole blood (Most numerous of blood cells). • Shape: Biconcave discs, 8 micrometers in diameter. • Red blood cells lack nucleus, ER, & mitochondria. • Production regulated by erythropoietin (hormone made in kidneys) • The kidneys produce the hormone erythropoietinto increase blood cell production when oxygen levels are low.

24. Red Blood Cells

26. Function of the Red Blood Cells • Transportation of oxygen to the tissues • Hemoglobin binds some carbon dioxide and carries it from the tissues to the lungs • The hemoglobin molecule is composed of two pairs of structurally different polypeptide chains • Each of the four polypeptide chains consists of a globin (protein) portion and heme unit, which surrounds an atom of iron that binds oxygen. • Each molecule of hemoglobin can carry four molecules of oxygen. • The production of each type of globin chain is controlled by individual structural genes with five different gene loci. • Mutations can occur anywhere in these five loci

27. Physiology of RBCs

28. Erythropoiesis • Red cells are produced in the red bone marrow after birth • Until age 5 years, almost all bones produce red cells to meet growth needs; after 5 years, bone marrow activity gradually declines • After 20 years, red cell production takes place mainly in the membranous bones of the vertebrae, sternum, ribs, and pelvis • With this reduction in activity, the red bone marrow is replaced with fatty yellow bone marrow

29. Steps in Erythropoiesis

30. Red Blood Cell Destruction • The red blood cell has a life span of approximately 120 days, so requires constant replacement. • It is broken down in the spleen. • Iron is reused by the red bone marrow where stem cells continually produce more red blood cells. • The heme molecule is converted to bilirubin and transported to the liver. • It is removed and turn into water soluble for elimination in the bile. • Lack of enough hemoglobin results in anemia.

31. Life Cycle of Red Blood Cells

32. Laboratory Tests for Red Blood Cells • Red blood cell count (RBC) • Measures the total number of red blood cells in 1 mm3 of blood. • Percentage of reticulocytes (normally approximately 1%) • Provides an index of the rate of red cell production. • Hemoglobin (grams per 100 mL of blood) • Measures the hemoglobin content of the blood. • Hematocrit • Measures the volume of red cell mass in 100 ml of plasma volume

34. C.B.C • Haemoglobin - 15±2.5, 14 ±2.5 - g/dl • PCV - 0.47 ±0.07, 0.42 ±0.05 - l/l (%) • Haematocrit, effective RBC volume - better • RBC count - 5.5 ±1, 4.8 ± 1 x1012/l • MCHC - Hb/PCV - 30-36 - g/dl • Hb synthesis within RBC • MCH - Hb/RBC - 29.5 ± 2.5 pg/l • Average Hb in RBC • MCV - PCV/RBC 85 ± 8 – fl • Average volume of red cells

35. Red Blood Cell Disorders

36. Anemia • Definition • An abnormally low number of circulating red blood cells or level of hemoglobin, or both • Low Hb <13.5 (males), <11.5 (females) • Results in diminished oxygen-carrying capacity. • Causes • Excessive loss or destruction of red blood cells • Deficient red blood cell production because of a lack of nutritional elements or bone marrow failure.

37. Anemia • Manifestations of Anemia • Impaired oxygen transport with the resulting compensatory mechanisms • Reduction in red cell indices and hemoglobin levels • Signs and symptoms associated with the pathologic process that is causing the anemia • fatigue, paleness, shortness of breath, and chills

38. Decreased production Nutritional Marrow suppression Marrow infiltration Increased loss Blood loss Hemolytic Immune Non immune Acquired: Decreased production Increased loss Congenital: Increased loss/Hemolytic Anemia Classification

39. Acquired RBC disorders • Decreased Production: • Aplastic, Hypoplastic anemias • Deficiency anemias Iron, B12, Folate etc. • Lack of erythropoiesis - Kidney disease • Marrow disease, malignancy, radiation • Increased loss/destruction: • Blood loss anemias - parasites, bleeding • Hemolytic anemias - Autoimmune (cold & warm antibody) mechanical, drugs & toxins.

40. Hemolytic Anemias • Inherited disorders • Membrane Disorders: • Spherocytosis, Elliptocytosis • Enzyme disorders: • Glucose-6-phosphate dehyrogenase and pyruvate kinase deficiencies. • Immune lysis (Warm & Cold Ab types). • Acquired hemolytic anemias: Infection induced (Clostridia, malaria, septicemia).

41. Hemolytic Anemias (Cont.) • Hemoglobinopathies • Sickle cell anemia (the presence of crescent- or sickle-shaped erythrocytes and accelerated hemolysis) • Thalassemia Syndromes , ,  (inherited disorders of hemoglobin metabolism in which there is a decrease in net synthesis of a particular globin chain without change in the structure of that chain).

42. Sickle Cell Disease

43. Anemias of Deficient Red Cell Production • Iron deficiency anemia (NormalSerum iron (1mg/l)). • Megaloblastic anemias • Cobalamin deficiency anemia. • Folic acid deficiency anemia.

44. Megaloblastic Anemia

45. Iron Deficiency Anemia • Common in developing world • Causes: • Blood loss – bleeding, parasites • Poor diet – malnutrition (greens & meat) • Increased need – Pregnancy, children • Pathogenesis: • Decreased Iron stores, • Decreased Hb Synthesis • Delayed maturation of erythroblasts • Decreased cell size (microcytes) • Decreased hb content (hypochromia) • Decreased RBC number, • Anemia.

46. Clinical Features • Anemia • Pallor, Weakness, Lethargy (A state of deep and prolonged unconsciousness) • Breathlessness on exertion • Palpitations may lead to heart failure - edema • IDA: • Angular cheilosis (inflammation and fissuring radiating from the commissures of the mouth) • atrophic glossitis, and dysphagia • koilonychia (a malformation of the nails) • gastric atrophy.

47. Iron Deficiency Anemia

48. Angular cheilitis & Glossitis

49. Koilonychia in Iron def.

50. Koilonychia in Iron def.