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Blood Hematology BLOOD: actually is a specialized CT with intercellular material comprised entirely of fluid. formed from undifferentiated mesenchyme of embryos (similar to other CT) - contains formed elements (blood cells) and plasma 1. In average human blood formed elements comprise 46% of blood volume, plasma 54% (hematocrit or pcv- packed cell volume) Men: 40-50% (5-6 million RBC's/mm3) Women: 35-45% (4-5 million RBC's/mm3) 2. Blood volume in average human about 5 L (8% of body weight) 3. Formed elements include: erythrocytes (RBC), leukocytes (WBC), platelets (thrombocytes which are cell fragments from megakaryocyte). Origin of blood: Blood cells originate in red bone marrow from hematopoietic stem cells (pluripotent or hematocytoblasts). These in turn will differentiate (progenitor cells) into the specialized blood cells. Erythropoietin (EPO): Hormone produced in the kidneys used to stimulate erythropoiesis in the bone marrow. EPO is produced in response to: - hypoxia - decrease in rbc count - decrease in hemoglobin conc. Anemia Refer to handout on common anemia's Blood: pH- 7.35-7.45 (arterial blood) - slightly alkaline 4-5x more viscous than water Blood temp. approx. 100F. Salt conc. .85-.90% (Saline?) - - Erythrocytes (RBC’s) Erythropoiesis: begin as immature proerythroblasts which in turn mature to a reticulocytes and ultimately an erythryocyte. Adult RBC production is approximately 200 billion RBC's /day. This means that RBC's are produced at the astonishing rate of 2 million/sec in healthy adults. RBC's outnumber WBC's about 800 to 1 Female: RBC count is 4-5 million/mm3 Male: RBC count is about 5-6 million/mm3 Characteristics: - anucleated - 7.5 micrometers in diameter - lacks other subcellular organelles as well - biconcave shaped (allows a 20-30% increase in surface area which increases efficiency of O2 and CO2 transport) - life span of 120 days The protein spectrin allows cell to flex and change shape to squeeze through capillaries. - Ability to carry O2 and CO2- hemoglobin Hemoglobin (Hb): - Protein found in rbc’s that bind O2. - Imparts reddish color to rbc. - Hemoglobin (Hb) in g/100 mL of blood 13-18 g of hemoglobin/100 mL of blood in adult males 12-16 g of hemoglobin/100 mL of blood in adult females - - Hb contains a structure called the porphyrin ring (also called heme) that is bound to a centrally located Fe molecule. - Each Hb can carry 4 O2's. One RBC contains 250 million Hb molecules (ie. 1 RBC can carry as many as 1 billion molecules of O2). - O2 is picked up in the lungs and binds to Hb along with H+. Hb is now called oxyhemoglobin (bright red arterial blood). - When O2 is dumped off in the tissues it is called deoxyhemoglobin. - When Hb picks up CO2 from tissues it binds to the protein portions of the Hb. Hb carrying CO2 is called carbaminohemoglobin. This gives venous blood its bluish color. Venous blood is not blue due to the decrease in O2 in the blood. Life cycle of an RBC 1- Nutrients (folic acid, Fe and Vit. B-12) are absorbed in the small intestine. 2- Nutrients go to red bone marrow 3- RBC’s develop from progenitor cells 4- RBC’s released in bloodstream and circulate for approx. 120 days 5- After 120 days, RBC’s are broken down by macrophages in the liver and spleen 6- Hb is broken down into heme and globin 7- Heme decomposes into Fe and a greenish substance called biliverdin 8- Iron binds to a protein called transferrin which ultimately travels to the red bone marrow to be recycled. (80% of Fe in the body is stored in the liver as ferritin) 9- Some biliverdin is converted to bilirubin, as yellowish/orange pigment found in bile –gallbladder. 10- Bilirubin travels into small intestine and 10 % is metabolized to urobilinogen (urochromes filtered in the liver) 11- 90% of bilirubin exits in the feces giving fecal matter its brown color (stercobilin) - RBC’s do not have mitochondria so they obtain their energy from anaerobic glycloysis (produce ATP) - primary component in this pathway is 2,3 diphosphoglycerate (2,3 DPG) - assists in unloading O2 in the tissues from the Hg in the RBC Leukocytes (WBC’): - Contain a nucleus plus all common organelles - 5,000-10,000/mm3 lab values - Have the ability to move once outside the blood (diapedesis) through fenestrations (holes) in the capillaries - Ability to be attracted to chemicals (chemotaxis) - Grouped according to the presence of granules in their cytoplasm (Chasing bacteria) Granular leukocytes/ granulocytes/ myeloblast series cells/ polymorphonuclear cells (PMN’s) - Neutrophils - Basophils - Eosinophils Agranular leukocytes (agranulocytes): - Monocytes - Lymphocytes WBC’s are involved in immune functions and are primarily active outside the blood stream. To remember granulocytic and agranulocytic “Every Boy Needs Mommies Love” To remember percentage of proportion “Never Let Monkeys Eat Bananas” NEVER: neutrophils (60%) LET: lymphocytes (30%) MY: monocytes (5%) ENGINE: eosinophils (4%) BLOW: basophils (0-1%) Neutrophil (lobed) Neutrophils: 2-5 lobes that are interconnected by fine strands (sometimes called “segs”) - acute inflammatory response and phagocytize bacteria, fungi and some viruses - circulate in blood for short period of time (10 hrs.) before migrating into tissues (5 days). - first white cell on the scene of an infection Neutropenia: too few neutrophils Neutrophilia: too many neutrophils Basophil - Basophils: Nucleus is typically bilobed Granules contain histamine and heparin Little ameboid and no phagocytic activity when basophil stimulated by an antigen or by tissue injury, responds by breaking open granulations causing histamine release. Histamine release initiates inflammatory reaction causing vasodilation and increasing permeability of blood vessels. - erythema - heat - plasma release Eosinophil - - - Eosinophil nucleus usually bilobed High number present in an allergic reaction. Phagocytize and kill larval stage of parasitic worms. Phagocytosis of the Ab/Ag complex found in an immune response Lymphocytes: - 30% of WBC population - Large dark purple nucleus - Small, medium and large - Majority are not found in circulating blood but in lymphoid tissue (nodes, spleen, marrow etc..) - Smallest WBC slightly larger than RBC - T- lymphocytes (immune response) - B- lymphocytes (antibodies-immunoglobins) We will cover these two lymphocytes in much detail under immunology Lymphocyte - - - - Monocytes: Largest of the WBC’s Nucleus is indented monocytes are phagocytic when monocytes leave bloodstream they rapidly transform to macrophages that are very active in ingesting bacteria, dead cells, tissue debris (“wandering macrophages”) Uses filopodia to search for things to eat - cytoplasmic extensions stimulate antibody production by lymphocytes. Monocyte - - - Platelets: Not cells but cell fragments Hemocytoblast Megakaryoblast Megakaryocyte 150,000 to 400,000/mm3 Anucleated Aid in blood clotting Arise from megakaryocytes in red bone marrow granulated: granules contain serotonin that aid in vasoconstriction Form a temporary plug when vessel is damaged. Formation is regulated by a hormone called thrombopoietin Platelets Plasma vs. serum: Plasma is an aqueous (92% water), straw colored solution containing proteins, lipids (digested nutrient), blood gases (O2, CO2 and N2), aminoacids, vitamins, hormones, and electrolytes (i.e. Na and Cl). The main plasma proteins are: 1- gamma globulins (immunoglobulins or antibodies)- lymphoid tissue 2- albumins (maintains osmotic pressure of blood) - liver 3- fibrinogen (clotting agent)- liver To obtain plasma, blood sample is spun down with an anticoagulant in the tube Serum: If blood is allowed to clot, the clear yellow liquid that separates out is called serum. Serum is similar to plasma but lacks fibrinogen and other clotting agents. To obtain serum, blood sample is spun down with no anticoagulant in the tube. Normal lab values of common substances dissolved in blood plasma/serum. Glucose: 70-110 mg/dl (fasting) Sodium (Na): 135 - 145 mEq/L Calcium (Ca): 8.5- 10.5 mEq/L Chloride (Cl): 98-106 mEq/L Potassium (K): 3.5 - 5.0 mEq/L Bicarbonate (HCO3): 18-23 mEq/L Hemostasis- blood stoppage Initial goal is to turn liquid (blood) into gel (coagulation). Steps: 1- smooth muscle in blood vessel wall contracts when vessel is damaged (vasospasm) -decrease blood loss, may seal off opening - slower flow of blood also helps platelets & coagulation. 2- attracted & stick to damaged vessel walls & to other sticky platelets -platelets release attractant chemicals that attracts other platelets -platelets release thrombospondins that aid platelet adhesion - platelet plug 3- Blood coagulation: Cascade of blood clotting chemicals. To form a blood clot a soluble plasma protein, fibrinogen (factor I), must be converted to insoluble threads called fibrin. Prothrombin (factor II) is a protein made in the liver and is a normal part of blood plasma. a. Prothrombin is converted to thrombin (factor II a). b. Thrombin fragments fibrinogen. c. Fibrinogen joins to form long slender threads of fibrin. d. Fibrin threads attach to the damaged blood vessels and more blood cells and platelets will stick. This mesh will form a blood clot. Under normal conditions clotting of blood in the body should only occur if blood remains stationary. Embolus vs. thrombus - Blood typing (ABO): Discovered in 1900 by Dr. Karl Landsteiner A – antigen A (40%) B – antigen B (10%) AB – antigen A & B (universal recipient 5%) O – no antigens (universal donor 45%) In the plasma: A: Antigen A in RBC Plasma: anti-B type antibodies B: Antigen B Plasma: anti-A type antibodies AB: antigen A&B Plasma: no anti-A or anti-B antibodies O: no antigens Plasma: both anti-A and anti-B antibodies Blood Type A Type of Antigen? A antigen Type of Antibody? Anti-B Receive? B B antigen Anti-A B, O AB Both A and B antigens None None A, B, AB, O Both Anti-A and Anti-B O only O A, O Type O Type B 45% Type A 42% Type AB 3% 10% Rh factor (Antigen D) Rh + = Rh factor antigen (marker) on RBC (85%) Rh - = no Rh antigen Rh- mother and Rh+ father: If baby inherits Rh+ from dad, mom’s blood will recognize baby’s blood as foreign and will attack it. - Erythroblastosis fetalis Blood typing Blood Type Presence of Type of Receive? D Antigen? Antibody? Rh Positive Yes None + and - No Anti-D - only Rh Negative