Hematopoiesis - PDF

Hematopoiesis Dr. Noor Hasan Baiee MBChB / F.I.C.M.S (Pathology/Hematology) Hematopathology Lecture for 4 th stage medical students Babylon University / College of medicine  Objectives 1. Know sites of hematopoiesis throughout life 2....

Hematopoiesis Dr. Noor Hasan Baiee MBChB / F.I.C.M.S (Pathology/Hematology) Hematopathology Lecture for 4 th stage medical students Babylon University / College of medicine  Objectives 1. Know sites of hematopoiesis throughout life 2. Describe the Structure of the bone marrow 3. Know the Significance of haemopoietic stem cell 4. Identify factors that Control hemopoiesis 6. Outline laboratory tests for Assessment of hemopoiesis 7. Define Red blood cell indices 8. Define anemia and Illustrate its classification Blood is a Suspension of differentiated mature non- dividing cells, (RBC,WBC and platelets The word Hematopoiesis refers to the production & development of all the blood cells: Erythrocytes (RBC): Erythropoiesis Leucocytes (WBC): Leucopoiesis Thrombocytes (platelets): Thrombopoiesis  Developmental sites of haemopoesis Prenatal; Fetus:(intrauterine) : – 0—2month (Yolk sac) – 2—7months (liver & spleen) – 5—9 months (bone marrow) Postnatal; Extra uterine: – Infant : Bone marrow (all bones) – Adult and elderly: Vertebrae, ribs, sternum, skull, pelvic bones and proximal ends of long bones  You Love a Smart Bunny Yolk Liver Spleen Bone marrow sac 7months—2 9months—5 2months—0 At other skeletal sites hematopoietic areas are replaced by fat cells. However, when there is increased demand for blood cell production , conversion of yellow fatty inactive marrow to red active marrow can occur. In extremely severe cases (e.g. severe chronic anemia), resumption of hematopoietic activity in organs other than bone marrow such as liver and spleen ( extramedullary hematopoiesis ) can occur. FIGURE  Histology (structure) of bone marrow The bone marrow consist of two parts , red marrow (parenchymal tissue) and supportive tissue. 1. red bone marrow: ; consist of four main (Parenchymal )cells types: o A. Stem cells. o B. cells of Erythropoiesis series (Stem cell, CFUE, Erythroblast ( early, intermediate and late erythroblast) – reticulocytes ). o C. Cells of myeloid series ( stem cell , CFUM, Blast, promyelocytes , myelocytes, metamyelocytes, band cells and mature granulocytes. o D. Megakaryocytes : precursor of platelets 2. Stromal supportive tissue (They form the environment for haemopoesis a. bone trabecular forming the architecture of bone marrow, b. network of microcirculation, c. supportive cells: macrophages, fatty cells, dendritic cells, and fibroblast Histology (structure) of bone marrow Stem cell; The Foundation of Hematopoisis All blood cells are derived from pleuripotent haematopoietic stem cells , It has the ability of proliferation, self-renewal, and differentiation along several lineages. Haemopoiesis starts with stem cell division in which one cell replaces the stem cell (self‐renewal ) and the other is ommitted to differentiation. The capacity of self-renewal permits life-long continuation of the process.  Stages of Hematopoiesis The myeloid and lymphoid stem cells originate from the pleuripotent hematopoietic stem cell. From myeloid and lymphoid stem cells progressively more committed progenitors arise. Red cells,granulocytes, monocytes, and platelets are derived from myeloid stem cell while B and T lymphocytes are formed from lymphoid stem cell through intermediate stages. Types of committed precursor cells: (1). Erythroid stem cells (CFU—E ): give mature Erythrocytes (RBC) (2) Myeloid stem cells (CFU—GM) : precursor of neutrophils, eosinophil, Basophils and monocytes. (3) Megakaryocytes stem cells : Thrombocytes (platelets) precursors.  Regulation of Hematopoiesis Hematopoiesis is tightly regulated by various factors including 1. Cytokines and interleukins 2. Hormones Erythropoietin(EPO) : Hormone produced by the kidney (90%) and liver (10%) Control erythroid proliferation and differentiation. Its secretion is stimulated by tissue hypoxia Thrombopoietin (TPO)  Thyroid hormones: Hemoglobin lever increase with increase thyroid hormone level Androgen : stimate erythropoiesis which is why hemoglobin levels are higher in male than female. 3. Growth factors : Colony growth factors: Stem cell-GF, GM-GF, Monocytes GF. G-CSF granulocyte colony stimulating factor GM-CSF granulocyte monocyte colony stimulating factor PDF FGF 4. Nutrients support : minerals (IRON) , vitamins (B12, folic acid, ), Amino acids are all crucial for blood cell production. 5. Bone marrow Microenvironment , and supportive cells Macrophages role in hemopoiesis (Has different functions): a. storage Iron in the bone marrow b. Denaturation of the aged red cells c. Release of cytokines and control hemopoiesis d. Defense mechanism  Erythropoisis Mature red blood cells develop from erythroblast in the bone Marrow. The development involves multiple stages with four mitotic divisions so that each precursor cell give rise to 16 mature red cells. The nucleus is expelled from the orthochromatic normoblast with the formationof a reticulocyte. The reticulocyte still has remnants of ribosomal RNA in the form of a cytoplasmic reticulum. After 1 to 2 days in the bone marrow and 1-2 days in peripheral blood reticulocytes lose RNA and become mature pink-staining erythrocytes Reticulocyte count is performed to assess erythropoietic activity of the bone marrow in a case of anaemia. In anaemia due to decreased red cell production or ineffective erythropoiesis, reticulocyte count is low. In anaemia with effective red cell production, reticulocyte count is high. Normal count (0.5-2.5%) Mature erythrocyte is a round biconcave disc about 7 to 8 μm in diameter. various red cell components (haemoglobin, enzymes, and membrane) Stages of Erythropoisis  Assessment of Hematopoisis 1. Hematocrit and Hb (PCV, hemoglobin), 2. CBC: erythrocytes count, leukocytes count, platelets count 3. Blood film ( for cells morphology) 4. Reticulocytes count 5. Bone marrow aspirate 6. Genetic tests  RBC indices 1. MCV (mean corpuscular volume) The average volume of RBC ( 80—100 fl) which classify anemia on cell size into microcytic100fl MCV= Htc (PCV)/ Red cells count 2. MCH (mean corpuscular hemoglobin) The average content of Hb in RBC. NR: 27-32 pg less than 27pg Hypochromic 27-32 normochromic MCH= Hb/ total Red cell count On blood smear hypochromic RBCS appear pale with increased central pallor to more than one third Hypochromia 3. MCHC (mean corpuscular hemoglobin concentration) Express the average concentration of hemoglobin per unit volume of RBC. MCHC= Hb/Htc (PCV) = NR: 32-36% 4. RDW ( Red cell Distribution Width) Red cell distribution width (RDW): degree of variation of red cell size increased RDW reflect anisopoikilocytosis.  Anemia Anemia is defined as a reduction in the haemoglobin concentration or oxygen-carrying capacity of blood below the level that is expected for healthy persons of same age and sex in the same environment. 13g/dl in adult male > 12g/dl in adult female >  Classification of Anemia The most useful classification is that based on red cell indices and divides the anemia into microcytic, normocytic and macrocytic Hypochromic (≥2/3 Normochromic Macrocytic central pallor) Normocytic microcytic (MCV