Hematology PDF

Unit 3: Hematology (Study of blood)  Objectives #1: Describe the Properties of blood Explain the functions of blood Describe the components of blood and their functions  Properties of Blood Viscosity – Blood thickness – contributes to flow Osmolarity...

Unit 3: Hematology (Study of blood)  Objectives #1: Describe the Properties of blood Explain the functions of blood Describe the components of blood and their functions  Properties of Blood Viscosity – Blood thickness – contributes to flow Osmolarity [solution] = total number of solute particles/L total molarity of dissolved particles/solutes – if too high, fluid absorption into the blood causes high BP – if too low, fluid remains in the tissues causing edema  Functions of Blood Blood transports substances throughout the body Functions in respiration, nutrition, waste elimination, thermoregulation, immune defense, water balance, and pH balance. What are the functions of blood? What materials are transported by blood? Why are these substances important? Be specific – explain why each of these substances contributes to homeostasis. What is blood and what does it do? What type of tissue is blood? Functions: 1. Transport of respiratory gases. 2. Regulation of pH. 3. Regulation of electrolytes. 4. Regulation of fluid loss, i.e., hemostasis. 5. Defense against pathogens. 6. Regulation of body temperature. 7. Transport of hormones. 8. Transport of nutrients and metabolic wastes.  Components of Blood Adults have 4-6 L of blood Two major components of blood: – Plasma Clear, extracellular fluid – Formed Elements/cells Blood cells and platelets 3. Name the 2 components of blood. What are the types of formed elements in the blood? What are their functions? Name 4. Describe the the 2 components components of blood. What are the types of formed of plasma. elements in the blood? What are their functions? Name the 2 components of blood.  Plasma 91 % water Pale yellow in color 9% - Mixture of proteins, ions, nutrients, waste products, regulatory products, and gases 4. Describe the components of plasma. Describe the components of plasma.  Plasma- Proteins Proteins in plasma- Almost all are produced by the liver or blood cells: Albumin- contributes to blood viscosity, acts as transport protein, maintains blood colloid osmotic pressure Globulins- Protects tissues, acts as transport protein, involved in immunity Fibrinogen- Functions in blood clotting Describe the components of plasma.  Plasma- Ions Involved in membrane potentials, osmosis, and pH balance: Sodium, potassium, calcium, magnesium, chloride, iron, phosphate, hydrogen, hydroxide, bicarbonate. Plasma-nutrients, waste products, regulatory products, and gases Nutrients- glucose, amino acids, triglycerides, cholesterol, vitamins Waste products- urea uric acid, creatinine, bilirubin, lactate Regulatory products- enzymes and hormones Gases- oxygen, carbon dioxide, nitrogen  Formed Elements Red Blood Cells = erythrocytes – Carry mostly oxygen and some carbon dioxide – hemoglobin White blood cells = leukocytes – Immunity, allergic response, antibody production and inflammation Platelets = thrombocytes – Hemostasis (clotting) What are the types of formed elements in the blood?  Erythrocytes (RBCs) Disc-shaped cell with a bi-concave shape (increases surface area!) Biconcave shape allows RBCs to stack – Rouleaux formation RBCs are flexible “bending” to circulate into small vessels (capillaries) Loss of all organelles (increase volume and diffusion rate) Describe how the shape of an RBC enables it to perform its functions. What proteins contribute to these functions?  Erythrocyte Functions Function is to transport gases – especially O2 Cytoplasm contains: – hemoglobin which carries 99% of body’s O2 and 20% of CO2 – Carbonic anhydrase for CO2 transport and pH balance (forms carbonic acid with CO2 and water) Leukocytes-WBCs  12. What are the functions of the different WBCs? What are What the functions are the of the different WBCs?two major What are types the two major typesof of WBCs? WBCs? Granulocytes- give examples Agranulocytes-give examples  12. What are the functions of the different WBCs? What are the two major Granulocyte Functions Neutrophils Increase in number during bacterial infections Phagocytize bacteria Release antimicrobial chemicals Eosinophils Increase during allergies or parasite infections Release enzymes to destroy multicellular parasites (such as worms) Phagocytize allergens and antigen/antibody complexes  Granulocyte Functions Basophils Increase during chicken pox, allergic reactions and trauma and also at the site of ectoparasite infections (such as a tick bite) Function during inflammation – Secrete histamines (vasodilators) – Secrete heparin (anticoagulant) 12. What are the functions of the different WBCs? What are the two major types?  Agranulocyte Functions Lymphocytes (T-cells and B-cells) Destroy cancer cells, foreign cells and body cells that are infected with a virus Present/advertise antigens to activate other immune cells Control the actions of other immune cells Secrete antibodies (B-cells) Provide immune memory 12. What are the functions of the different WBCs? What are the two major types?  Agranulocyte Functions Monocytes Increase during viral infections and inflammation Differentiate to become macrophages Phagocytize pathogens and debris Present antigens to activate other immune cells 12. What are the functions of the different WBCs? What are the two major types?  Platelets Amoeboid movement and phagocytosis Contain granules Functions – secrete clotting factors, growth factors for endothelial repair, and vasoconstrictors in broken vessels – form temporary platelet plugs – dissolve old blood clots – phagocytize bacteria – attract WBCs to sites of inflammation Describe the role of platelets and the process by which a clot is 14. What formed is the and also function dissolved. of platelets? (Answer found on slide 63)  Objective #2: Name the four basic blood types. Explain how blood typing is performed. Explain the clinical significance of blood testing. (If provided with a hypothetical situation, be able to predict the results). Four Basic Blood Types How does the blood typing test work? If provided with a hypothetical situation, be able to predict the results.  ABO Blood Typing Background information: Antigen = molecule (glycoproteins) on the surface of a cell (allow “normal cells” to be ignored and foreign cells to be attacked) Antigens on surface of RBCs are agglutinogens Antibody = molecule built to recognize and combat foreign antigens – Anti-A and Anti-B – Cause agglutination/clumping in mismatched blood transfusions Your ABO blood type is determined by the presence or absence of antigens on your RBCs  Antibody-Antigen Relationship Fit together like puzzle pieces Antibodies bind to antigens Antibodies stick or clump (agglutinate) together Agglutination Blood Typing What happens during a mismatch? Agglutinated RBCs can lyse (break apart) and block blood vessels Free hemoglobin proteins can block kidney tubules and cause kidney failure (and death) Blood Typing  What about negative and positive? In addition to A and B, Rh is an antigen of concern on blood cells. Presence of Rh is positive, absence of Rh is negative Can cause problems during pregnancy if mother has negative blood type and baby is positive 85% of population is Rh+  Rh and pregnancy Anti-Rh antibodies are not normally present in the blood (form only when you are exposed to Rh antigens) No problems with the first pregnancy but hemolytic disease of the newborn occurs in the second pregnancy if the mother formed antibodies from the first pregnancy RhoGAM (Rh-immunoglobulin) is given to pregnant woman to prevent antibody formation RhoGAM binds fetal RBCs in her blood so she will not form antibodies against them during the pregnancy  Objectives #3 Define hematopoiesis. Explain how red blood cells are formed. Describe hemoglobin and its function. Describe how erythrocyte homeostasis is maintained. Explain how white blood cells are formed. Explain how platelets are formed.  Definitions: Hemopoietic – forming blood OR blood cells Yolk sac- a structure outside the embryo vital during the first trimester of pregnancy (Fxn: endocrine, metabolic and hemopoietic) Hemocytoblast-stem cell from which all blood cells are produced Pluripotent- capable of giving rise to many cell types  Hematopoiesis Hematopoietic tissues produce blood cells – yolk sac in vertebrate embryo produce stem cells that colonize fetal bone marrow, liver, spleen and thymus – liver stops producing blood cells at birth, but spleen and thymus remain involved with WBC production – 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 erythropoietin (EPO), thrombopoietin and other colony-stimulating factors (CSFs) Lots of vocabulary to address in this slide!  Hematopoietic Stem Cell Lineages All blood formed elements are derived from hemocytoblasts (stem cells) Hemocytoblast Explain how the hemocytoblast differentiates into multiple lineages. Stages in RBC Maturation Explain the stages/process of RBC maturation. Don’t forget the critical components required for this process!  Erythrocyte Production Erythropoiesis produces 2.5 million RBCs/second from stem cells (hemocytoblasts) in red bone marrow Development takes 3-5 days 1. First committed cell is proerythroblast – has receptors for erythropoietin (EPO) from kidneys; EPO stimulates development of erythroblast 2. Erythroblasts multiply and synthesize hemoglobin 3. Normoblasts discard their nucleus and other organelles to form a reticulocyte – Reticulocyte enters bloodstream (0.5 to 1.5% of circulating RBCs are reticulocytes) 4. After 24 hours reticulocyte has completed maturation= RBC  Structure of Hemoglobin Hemoglobin consists of 4 protein chains called globins (2 alpha and 2 beta) Each protein chain is conjugated with a heme group which binds oxygen to Fe+2 – heme is ring shaped molecule that binds iron Single hemoglobin molecule can carry four O2 10. Why is iron homeostasis important? How is it maintained? What proteins Explain how theand organs structure are of hemoglobin contributes to its function. involved?  Nutritional Needs for Erythropoiesis - Iron Iron is a key nutritional requirement – low absorption rate requires consumption of 5-20 mg/day – absorbed into blood; binds to transferrin in blood for transport – red bone marrow stores iron, muscle uses to make myoglobin and all cells use it to make mitochondrial proteins – liver stores surplus as ferritin 10. Why Why is iron is iron homeostasis homeostasis important? important? How is it maintained? What How is it maintained? proteins What proteins and and organs are involved? organs are involved?  Nutritional needs cont. B12 and folic acid – for rapid cell division vitamin C and copper – vitamin C aids in dietary absorption of iron – copper is required for iron transfer Vitamin C Note: Calcium inhibits iron absorption.  Erythrocyte Homeostasis Stimuli for erythropoiesis – low levels of O2 (hypoxemia) Detected by circulating blood in the kidneys, liver and carotid bodies increase in exercise high altitude hemorrhaging Negative feedback control – hypoxemia in kidneys – Erythropoietin (EPO) production ↑ – stimulation of bone marrow Describe the regulation of – RBC count ↑ in 3-4 days RBC concentration. How does the kidney impact RBC homeostasis?  Leukocyte production/Leukopoiesis B and T progenitor lymphocytes – differentiate into B cells and T cells – T-cells leave the marrow unfinished and go to the thymus to complete their development Describe the process of leukopoiesis.  Leukocyte production/Leukopoiesis Hematopoietic stem cell -> myeloid progenitor cells – differentiate into neutrophils, basophils, eosinophils or monocytes Q:How do stem cells (hematopoietic cells) know when to differentiate? A:They have receptors for colony stimulating factors (regulatory molecules)  Platelet production (thrombopoiesis) Some hemocytoblasts have receptors that respond to thrombopoietin (produced by liver and kidneys) and activate to become megakaryoblasts Megakaryoblast replicates its DNA repeatedly without dividing The resulting huge cell is called a megakaryocyte and remains in the bone marrow. Small fragments split off the cell to become platelets/thrombocytes Life span 7 to 10 days  Objectives # 4 Define hemostasis. Describe the three different mechanisms that can lead to hemostasis. Describe how a clot formation is regulated. Explain how clots are dissolved.  Hemostasis – Mechanism of Controlling/Stopping Bleeding A positive feedback cycle Prevents excessive blood loss Three processes: – Vascular spasm – Platelet plug – Coagulation (clotting)  15. What causes vascular spasm? Why Vascular spasm Quick constriction of a broken blood vessel Provides immediate but temporary solution Occurs several times a day as BVs are injured Stimuli for spasm: – Injury to smooth muscle causes pain receptors activation (nervous system reflexes lead to vasoconstriction) – Platelets release serotonin which is a vasoconstrictor – Damaged endothelial cells in the vesselWhat wall release causes vascular spasm? Why endothelin (will constrict the vessels) is it important in hemostasis?  Platelet plug formation Not the same as a “blood clot” Normal vessel endothelium is smooth and covered in prostacyclin Prostacyclin's function to prevent platelet activation in a healthy blood vessel Broken vessels expose rough surfaces of collagen fibers, thus activating platelet plug formation What causes a platelet plug to be formed? Why is it important to hemostasis?  Platelet Plug formation What causes platelet plug 16. formation? Why is it important in hemostasis? Positive feedback cycle Involves several steps: adhesion activation aggregation Coagulation-secretion of clotting factors (required for the repair of large tears or cuts)  Platelet Plug formation Platelet adhesion- the initial step in platelet plug formation when platelets bind to exposed collagen fibers and release chemicals (ADP and thromboxane) to activate other platelets Platelet activation- Activated platelets change their shape and express fibrinogen receptors allowing for binding to fibrinogen (remember, this is a blood plasma protein) Platelet aggregation- The binding of fibrinogen creates a “bridge” between different platelets The bridging creates the platelet plug  Coagulation Required for larger tears and cuts to blood vessels It is the formation of a blood clot (a network of fibers that trap blood cells, platelets, and fluids) – The network is formed by protein fibers called fibrin Dependent on release of clotting factors (proteins produced by the liver and found in blood plasma) Note: Clot formation may increase in late stage cancers Describe the role of platelets and the process by which a clot is formed and also dissolved.  18. How are clots dissolved? How are they prevented? Clot Retraction and Dissolution Clot retraction occurs immediately after formation to condense the structure which “sticks” to the walls of the blood vessel. Retraction pulls on edges of BV walls (how the bleeding is managed/stopped) A blood clot usually dissolves a few days after it forms – Process of dissolution is called fibrinolysis – Plasminogen converts to plasmin, the enzyme responsible for breaking fibrin which then dissolves the clot How are clots dissolved?  Objectives #5 Describe the risk groups, symptoms, signs, causes, preventions, and treatments for select blood disorders/diseases Homeostatic Imbalances of Blood Know the risk groups, symptoms, signs, causes, preventions, and treatments for each of the blood-related disorders described in the unit.  Leukemia Cancer of leukocytes There are a variety of types of leukemia Acute – sudden onset with rapid division of abnormal WBCs. Chronic – slow growth of abnormal cells (Adults can get either kind but children are typically diagnosed with acute forms) Treatments include chemotherapy, stem cell transplants and radiation  Hemophilia Bleeding disorder caused by a mutation in the genes for making clotting factors (usually clotting factor VIII or IX) The genes are located on the X chromosome which means hemophilia is a sex linked genetic disease It is a recessive disease Disease is most prevalent in men Queen Victoria’s Family Pedigree  Hemophilia cont. Symptoms include: spontaneous bleeding and bleeding following injuries or surgery. Also: swollen joints due to bleeding at joints, frequent bruising, blood in the stool and or urine, and bleeding gums. Treatment: replace the missing clotting factors by infusion.  Erythroblastosis fetalis Condition in a pregnant woman due to Rh incompatibility with the fetus If a mother is Rh negative and the child in womb is Rh positive then the mother may make antibodies against the child’s blood type. Typically becomes a problem after a first pregnancy. The antibodies from the mother will destroy the babies blood cells making the baby anemic  Sickle cell anemia An autosomal recessive genetic disease Caused by a mutated beta hemoglobin gene (HBB gene) which results in the formation of improperly shaped hemoglobin proteins. Symptoms: pain, anemia, vulnerable to repeat infections, shortness of breath, fatigue and delayed growth (in children)  Thrombocytopenia Low platelet count Can be inherited, caused by leukemia or immune system conditions or it can be drug induced (some medicines can cause it) Symptoms: excessive bleeding and bruising, blood in urine, unusually heavy menstrual flow