BIO 3324 1nd Edition Lecture 16Outline of Last LectureI. venules&veinsII. blood flowIII. bulk flowIV. sympathetic control V. bloodVI. plasmaOutline of Current LectureI. plasma proteinsII. blood flowIII. hemoglobinIV. RBCV. clotting cascadeVI. thrombinCurrent lecture: Plasma proteins:• Establish the osmotic gradient between blood and interstitial fluid• Partly responsible for buffering• Albumins – most abundant (60%) – non-specifically bind many substances for transport• Globulins (a, b, g)– Bind poorly soluble substances for transport (highly specific)– Involved in blood clotting– Regulatory proteins (a-globulins; e.g. convert angiotensinogen into angiotensin)These notes represent a detailed interpretation of the professor’s lecture. Grade Buddy is best Used as a supplement to your own notes, not as a substitute.– Immune response (g-globulin, aka antibodies, immunoglobulin)• Fibrinogen – key role in blood clotting• Transferrin – iron transporting proteinHematocrit:• Packed cell volume• Represents % erythrocytes (42-45% blood volume)• 1% blood volume = other blood cells– “Buffy Coat”• Remaining volume is plasmaThe cellular elements:• Erythrocytes (Red Blood cells)• Leukocytes (White Blood cells)– Only group of functional cells– Mobile units of immune system– 5 types classified by function or morphology• Mononuclear agranulocytes – single nucleus; lack granules– Monocytes (“phagocytes”), lymphocytes (“immunocytes”)• Polymorphonuclear granulocytes – multi-lobe nucleus; contain granules– Neutrophils, eosinophils, basophils• Thrombocytes (platelets)– Cell fragments derived from megakaryocytes– Responsible for hemostasisBlood cell production:• Hematopoiesis• All blood cells descend from a single precursor cell called a pluripotent hematopoietic stem cell found primarily in bone marrow.• Differentiation is under control of cytokines– “Hormones” include erythropoietin (RBCs) & thrombopoietin (megakaryocytes)– Colony stimulating factors regulates the formation of leukocytes – Interleukins play multiple rolesErythrocytes(red blood cells)• 5x109 cells/ml blood• Responsible for the transport of O2• Flat, disc-like, bi-concave discs– Provides a larger surface area for diffusion of O2 across the membrane– Allows for O2 to diffuse rapidly between interior and exterior of cell• Extremely pliant – can squeeze through narrow capillaries easily• Lack organelles & Nuclei– Essentially a plasma membrane sac containing hemoglobin• Contain Hemoglobin– 250x106 molecules of hemoglobin/cellHemoglobin:• Globin portion – four polypeptide chain• 4 heme groups – nonprotein pigment, contains iron– Can bind reversibly with O2• Can also combine with:– CO2 (carries from tissues to lungs)– H+ from carbonic acid (acts as a buffer)– CO– NO (vasodilator)• Hemoglobin synthesis– Iron enters via the diet– Absorbed by sm. int by active transport– In blood, it binds to & is transported by transferrin– In bone marrow, iron is used to create heme– Excess iron is stored in the liver attached to ferritin & derivativesEnzymes of significance in the RBC• Glycolytic enzymes– Help to fuel the cell’s transport machinery & maintain proper ionic concentration– RBCs rely entirely on glycolysis for energy production• Carbonic Anhydrase– Critical for CO2 transport– Catalyst in the CO2 to HCO3- reaction• How CO2 is transported in the bloodRBC lifespan:• Lacks DNA, RNA, nor cell machinery for repair, growth or division• Survives ~120 days• Typically taken up by the spleen & removed from circulationErythropoiesis:• Occurs in red bone marrow– During in utero development – different tissues• Initially yolk sac, then liver & spleen– During childhood – most bones contain red bone marrow– During adulthood – sternum, ribs, upper ends of the long bones• Regulated by the kidney in response to less O2 arriving in the blood (reduced oxygen-carrying capacity)– Results from less RBCs circulating• Anemia: Below normal O2-carrying capacity of blood• Characterized by a low hematocrit• Caused by:– Excessive loss of RBC– Decreased rate of erythropoiesis– Deficiency in hemoglobin content• Six categories• Types of anemia: Nutritional anemia – dietary deficiency of a factor needed for erythropoiesis. E.g., iron deficiency• Pernicious anemia – inability to absorb Vitamin B12 for erythropoiesis– Caused by deficiency in intrinsic factor – secreted by the lining of the stomach• Aplastic anemia – failure of the bone marrow to produce RBC– Failure of erythropoietic machinary• Renal anemia – inadequate Erythropoietin secretion• Hemorrhagic anemia – loss of blood• Hemolytic anemia – rupture of circulating RBC by external factor. E.g., Sickle CellPolycythemia:• Too many circulating RBCs• Primary – erythropoiesis proceeds at excessive, uncontrolled rate– Increased blood viscosity– Increased total peripheral resistance• Secondary – appropriate erythropoietin-induced adaptive mechanism in response to prolonged reduced O2 deliveryPlatelets(thrombocytes):• Not whole cells, but are cell fragments from Megakaryocytes– Contain organelles & cytosolic elements• Function ~10 days then removed by macrophages• Thrombopoietin released by liver responsible for increased megakaryocyte production• Stored in spleen (1/3 of total circulating number)• Functional role in hemostasisHemostasis:• Arrest of bleeding from a broken blood vessel• Involves 3 major steps– Vascular spasm– Formation of platelet plug– Blood coagulation (clotting)Vascular spasm:• Cut/torn blood vessel immediately constricts• Slows blood flow• Opposing endothelial surfaces are pressed together further sealing off blood flow• Platelet plug: Aggregation of platelets at the tear– Normally do not adhere to endothelial walls, but will adhere to exposed collagen• Release of platelet factors to cause more platelets to aggregate & cause adjacent endothelium to release anti-aggregating chemicals to limit platelet aggregation– Chemicals released to induce vasoconstriction to reinforce vascular spasm– Release factors to promote clotting• Actin/myosin complex within platelet contract to tighten & strengthen plug• Serves to seal the break• Clot formation: Requires the conversion of fibrinogen into fibrin by the enzyme, thrombin at site