Introduction of hematology for reassessment ppt
- 2. What is What is hematology hematology ? ? Hematology is the study of blood. Hematology is the study of blood. Blood: is the fluid where the cells Blood: is the fluid where the cells are free and suspended. are free and suspended. It can cross the tissues. It can cross the tissues. has red color. has red color. Has volume of 5-6 liters, this is 7- Has volume of 5-6 liters, this is 7- 8% of the total body weight. 8% of the total body weight.
- 3. Has PH of 7.3-7.4 (alkaline). Has PH of 7.3-7.4 (alkaline). Specific gravity is 1.055-1.056 Specific gravity is 1.055-1.056 It is composed of plasma (~53-58% It is composed of plasma (~53-58% of the blood volume), before of the blood volume), before clotting occurs, and serum after clotting occurs, and serum after clotting occurs. clotting occurs. Plasma consists of 91-92% water, Plasma consists of 91-92% water, and 8-9%solids. and 8-9%solids.
- 5. Solids are: Solids are: Albumin. Albumin. Glucose. Glucose. Fibrinogen. Fibrinogen. Sodium. Sodium. Calcium. Calcium. Potassium. Potassium. Cholesterol. Cholesterol. Magnesium. Magnesium. Carbon dioxide. Carbon dioxide. Phosphorus. Phosphorus. Neutral fats. Neutral fats. NPN group. NPN group. Oxygen. Oxygen. Many other Many other products. products.
- 6. Also there are such substances, like Also there are such substances, like antibodies, hormones, complement and antibodies, hormones, complement and enzymes. enzymes. Cellular parts of the blood (45-47%): Cellular parts of the blood (45-47%): Consists of: Consists of: – The erythrocytes (RBCs) (~45%) The erythrocytes (RBCs) (~45%) Contain hemoglobin Contain hemoglobin Function in the transport of O Function in the transport of O2 2 and and CO CO2 2
- 8. • The Leukocytes The Leukocytes (WBCs) and platelets (WBCs) and platelets (thrombocytes) (~1%) (thrombocytes) (~1%) Leukocytes are involved in the Leukocytes are involved in the body’s defense against the invasion body’s defense against the invasion of foreign antigens. of foreign antigens.
- 10. Platelets Platelets are involved in hemostasis which are involved in hemostasis which forms a barrier to limit blood loss forms a barrier to limit blood loss at an injured site. at an injured site.
- 12. The cells are forming about 45-47% The cells are forming about 45-47% of the total blood volume in male and of the total blood volume in male and 42% in female. This percentage is 42% in female. This percentage is determined by centrifugation and is determined by centrifugation and is known as heamatocrit (PCV), which known as heamatocrit (PCV), which is the percentage of the packed red is the percentage of the packed red blood cells. blood cells.
- 13. Functions of the blood Functions of the blood : :
- 14. 1. 1. Nutritive: The blood transports Nutritive: The blood transports nutrients from the gut to all parts of nutrients from the gut to all parts of the body for use or storage. the body for use or storage. 2. 2. Respiratory: the blood carries the Respiratory: the blood carries the oxygen to the tissue and remove oxygen to the tissue and remove carbon dioxide and other waste carbon dioxide and other waste products from the tissues to be products from the tissues to be excreted by the lung, kidney, liver, excreted by the lung, kidney, liver, and skin and skin
- 15. 3- 3- The blood regulates the temperature of the The blood regulates the temperature of the body, because it is constantly in motion. body, because it is constantly in motion. 4- Transportive: The blood transports the 4- Transportive: The blood transports the hormones from the endocrine glands to the hormones from the endocrine glands to the tissues. tissues. 5- Excretory: To excrete the waste products 5- Excretory: To excrete the waste products of metabolism, for example urea, and uric of metabolism, for example urea, and uric acid. acid. 6- Protection: versus invading microorganisms
- 16. Blood Cell Production (Hematopoiesis or hemopoiesis) Hematopoiesis is a term describing the formation and development of blood cells. In humans, occurs in bone marrow exclusively All cellular elements derived from pluripotent stem cell (PPSC) PPSC retains ability to both replicate itself and differentiate Types of differentiation determined by the influence of various cytokines Only mature cells are released into the peripheral blood.
- 17. Why do we need the Hematopoiesis ? –Cells of the blood are constantly being lost or destroyed. Thus, to maintain homeostasis, the system must have the capacity for self renewal.
- 18. Sites of production Sites of production : : – Fetus: Fetus: 0-2 months (yolk sac). 0-2 months (yolk sac). 2-7 months ( liver and 2-7 months ( liver and spleen). spleen). 5-9 months (bone marrow). 5-9 months (bone marrow). – infants: bone marrow infants: bone marrow – Adults: bone marrow, ribs, sternum, skull, Adults: bone marrow, ribs, sternum, skull, sacrum and pelvis. sacrum and pelvis.
- 19. – Hematopoiesis in the bone marrow is called Hematopoiesis in the bone marrow is called medullary hematopoiesis medullary hematopoiesis – Hematopoiesis in areas other then the bone Hematopoiesis in areas other then the bone marrow is called marrow is called extramedullary extramedullary hematopoiesis hematopoiesis – Extramedullary hematopoiesis may occur in fetal hematopoietic tissue (liver and spleen), and in adult when the bone marrow cannot meet the physiologic needs of the tissues. This can lead to hepatomegaly and/or splenomegaly (increase in size of the liver or spleen because of increased functions in the organs).
- 20. Hematopoietic tissues ARE: Hematopoietic tissues ARE: Includes tissues involved in the Includes tissues involved in the proliferation, maturation, and proliferation, maturation, and destruction of blood cells destruction of blood cells
- 21. Derivation of blood cells - The committed lymphoid stem cells will be involved in lymphopoiesis to produce lymphocytes - The committed myeloid stem cell can differentiate into any of the other hematopoietic cells including erythrocytes, neutrophils, eosinophils, basophils, monocytes, macrophages, and platelets.
- 22. 1. Erythrocyte: • Normal erythrocyte is a round highly flexible biconcave discs like cell; it is non-nucleated, containing haemoglobin. • It measures about 7.2-7.8 microns, 80-100 femtoliters in volume • Flexibility essential for passage through capillaries • Life span: the average is 80-120 days. • Function: RBC carry oxygen from the lung to the body cells and carry carbon dioxide from the body cells to the lung.
- 25. Terminology : Erythrocytosis: increased in the blood cells count, which may lead to Reticulocyte: is a very young erythrocyte which contains remainant of RNA. The precipitated RNA is seen when stained with a supravital stain such as new methylene blue or brilliant crystal blue dyes. Reticulocytosis: increased blood reticulocyte count. Thrombocytopenia : decrease platelets number in the blood Thrombocytosis: increase platelets number in the blood
- 26. 1. Splenectomy (removal of the spleen), Hypersplenism (splenomegaly) – in a number of conditions the spleen may become enlarged. 2. Leukopenia decreased WBCs count. 3. Leukocytosis: increased WBCs count. 4. Pancytopenia: when all three cell types are decreased, which may lead to anaemia. 5. Polycythemia which is an increasing in the Hg concentration above 17.5 g/dl in adult males and 15.5 g/dl in adult females, with elevated haematocrit and RBCs count.
- 27. Blood Cell Production Blood Cell Production (Hemopoiesis) (Hemopoiesis) Red bone marrow produces RBCs, WBCs and platelets Stem cells called hemocytoblasts multiply continually and are pluripotent (capable of differentiating into multiple cell lines) committed cells are destined to continue down one specific cell line Stimulated by different Cytokines: erythropoietin, thrombopoietin and colony stimulating factors (CSFs).
- 28. B. Erythropoietin and Its B. Erythropoietin and Its Receptor Receptor : : Cytokine – 90% is produced in the kidney and the rest is produced in a variety of extrarenal sites. Necessary for erythroid proliferation and differentiation Absence results in apoptosis (programmed cell death) of erythroid committed cells Anemia of renal failure leads to lack of EPO
- 29. The signal that causes erythropoietin-secreting cells to synthesize and release the cytokine is hypoxia. Whenever the oxygen level within the cytoplasm of erythropoietin-producing cells falls below a critical level, erythropoietin is synthesized in the kidney and secreted into the bloodstream. Once synthesized and released from the cell, erythropoietin travels in the bloodstream to the bone marrow, where it binds to receptors on erythroid cells, thereby initiating their proliferation and differentiation.
- 30. Erythrocyte Homeostasis: Classic negative feedback control Hypoxemia in kidneys leads to increased EPO production Stimulation of bone marrow RBC count in 3-4 days ↑
- 31. Stimuli for erythropoiesis Low levels of O2 Increase in exercise Hemorrhaging
- 33. RBC Precursors 1.Pronormoblast or Proerythroblast. 2.Basophilic (early) normoblast 3.Polychromatophilic (intermediate) Normoblast 4.Orthrochromatophilic ( late) Normoblast 5.Reticulocyte 6.Mature Red Blood Cell
- 34. Erythrocyte Production Erythropoiesis produces 2.5 million RBCs/second from stem cells (hemocytoblasts) in bone marrow Pronormoblast has receptors for erythropoietin (EPO) from kidneys; EPO stimulates development of erythroblast Erythroblasts multiply & synthesize hemoglobin (late normoblast and reticulocyte).
- 35. Late Normoblasts discard discard their nucleus to form a reticulocyte (named for fine network of endoplasmic reticulum) Reticulocyte Enters bloodstream as 0.5 to 1.5% of circulating RBCs Development takes 3-5 days This mechanism will involve reduction in cell size, increase in cell number, synthesis of hemoglobin & loss of nucleus Blood loss speeds up the process increasing reticulocyte count
- 41. RETICULOCYTE : Young red blood cell; still have small amounts of RNA present in their cytoplasm Tend to stain somewhat bluer than mature RBC’s on Wright stain (polychromatophilic) Slightly larger than mature RBC Undergo removal of RNA on passing through spleen, in 1st day of life Can be detected using supravital stain
- 42. Nutritional Needs for Erythropoiesis Iron : is key nutritional requirement for erythropoiesis Lost daily through urine, feces, and bleeding Dietary iron in 2 forms: ferric (Fe+3) and ferrous (Fe+2) Stomach acid converts Fe+3 to absorbable Fe+2 Gastroferritin from stomach binds Fe+2 & transports it to intestine
- 43. Absorbed into blood & binds to Absorbed into blood & binds to transferrin transferrin to travel bone marrow uses to travel bone marrow uses to make to make hemoglobin hemoglobin, , muscle muscle used to used to make myoglobin and all cells use to make myoglobin and all cells use to make make cytochromes cytochromes in mitochondria in mitochondria Liver binds surplus to apoferritin to Liver binds surplus to apoferritin to create ferritin for storage create ferritin for storage 2-B12 & folic acid 2-B12 & folic acid (for rapid cell division). (for rapid cell division). 3-Vitamin C & copper 3-Vitamin C & copper (for cofactors for (for cofactors for enzymes synthesizing RBCs) enzymes synthesizing RBCs)
- 44. 2 2 - - Leukocyte Production (Leukopoiesis) Leukocyte Production (Leukopoiesis) Committed cell types -- B and T progenitor Committed cell types -- B and T progenitor lymphocytes and granulocyte-macrophage lymphocytes and granulocyte-macrophage colony-forming units colony-forming units Possess receptors for colony-stimulating Possess receptors for colony-stimulating factors released by factors released by mature WBCs in in response to infections response to infections Red bone marrow Red bone marrow stores and releases stores and releases granulocytes and monocytes granulocytes and monocytes Some lymphocytes leave bone marrow Some lymphocytes leave bone marrow unfinished go to unfinished go to thymus thymus to complete their to complete their development (T cells) development (T cells)
- 45. Circulating WBCs do not stay in Circulating WBCs do not stay in bloodstream bloodstream Granulocytes leave in 8 hours & live 5 Granulocytes leave in 8 hours & live 5 days longer days longer Monocytes leave in 20 hours, Monocytes leave in 20 hours, transform into macrophages and live transform into macrophages and live for several years for several years WBCs providing long-term immunity WBCs providing long-term immunity (lymphocytes) last decades (lymphocytes) last decades
- 47. Leukocyte Descriptions (WBCs) Leukocyte Descriptions (WBCs) Granulocytes Granulocytes – eosinophils - 2-4% eosinophils - 2-4% – basophils - <1% basophils - <1% – neutrophils - 60-70% neutrophils - 60-70% Agranulocytes Agranulocytes – Lymphocytes (B and T cells) - 25- Lymphocytes (B and T cells) - 25- 33% 33% – Monocytes - 3-8% Monocytes - 3-8%
- 48. Granulocyte Functions Granulocyte Functions Neutrophils Neutrophils (↑ in bacterial infections) (↑ in bacterial infections) Phagocytosis of bacteria Phagocytosis of bacteria Releases antimicrobial chemicals Releases antimicrobial chemicals Eosinophils Eosinophils ↑ ↑ in parasitic infections or allergies in parasitic infections or allergies Phagocytosis of antigen-antibody complexes, allergens & Phagocytosis of antigen-antibody complexes, allergens & inflammatory chemicals inflammatory chemicals Release enzymes destroy parasites such as worms Release enzymes destroy parasites such as worms Basophils Basophils (↑ in chicken pox, sinusitis, diabetes) (↑ in chicken pox, sinusitis, diabetes) Secrete histamine (vasodilator) Secrete histamine (vasodilator) Secrete heparin (anticoagulant Secrete heparin (anticoagulant
- 49. Agranulocyte Functions Agranulocyte Functions Lymphocytes (↑ in diverse infections & immune Lymphocytes (↑ in diverse infections & immune responses) responses) Destroy cancer & foreign cells & virally infected Destroy cancer & foreign cells & virally infected cells cells “ “Present” antigens to activate other immune cells Present” antigens to activate other immune cells Coordinate actions of other immune cells Coordinate actions of other immune cells Secrete antibodies & provide immune memory Secrete antibodies & provide immune memory Monocytes (↑ in viral infections & inflammation) Monocytes (↑ in viral infections & inflammation) Differentiate into macrophages Differentiate into macrophages Phagocytize pathogens and debris Phagocytize pathogens and debris “ “Present” antigens to activate other immune cells Present” antigens to activate other immune cells (APC) (APC)
- 50. Platelet Production (Thrombopoiesis) Platelet Production (Thrombopoiesis) Hemocytoblasts that develop receptors for Hemocytoblasts that develop receptors for thrombopoietin thrombopoietin from from liver or kidney liver or kidney become megakaryoblasts become megakaryoblasts Megakaryoblasts repeatedly replicates its Megakaryoblasts repeatedly replicates its DNA without dividing forms gigantic cell DNA without dividing forms gigantic cell that remains in bone marrow called that remains in bone marrow called megakaryocyte (100 μm in diameter) megakaryocyte (100 μm in diameter) Infoldings of megakaryocyte cytoplasm Infoldings of megakaryocyte cytoplasm splits off cell fragments that enter the splits off cell fragments that enter the bloodstream as platelets (live for 10 days) bloodstream as platelets (live for 10 days) Some stored in spleen and released as Some stored in spleen and released as needed needed
- 51. Platelets Platelets Small fragments of megakaryocyte Small fragments of megakaryocyte cytoplasm cytoplasm 2-4 μm diameter & containing 2-4 μm diameter & containing “granules” “granules” Pseudopods provide amoeboid Pseudopods provide amoeboid movement & phagocytosis movement & phagocytosis
- 52. Functions Functions : : Secrete clotting factors, growth factors Secrete clotting factors, growth factors for endothelial repair, and for endothelial repair, and vasoconstrictors in broken vessels vasoconstrictors in broken vessels Form temporary platelet plugs Form temporary platelet plugs Dissolve old blood clots Dissolve old blood clots Phagocytize bacteria Phagocytize bacteria Attract WBCs to sites of inflammation Attract WBCs to sites of inflammation