BME 501Advanced Topics in Biomedical SystemsSpring 2014Dr. KayBME 501 Lecture Notes – Mar 10Overview of Circulation and Blood• Components of the blood– Plasma– Blood Cells• Hemostasis– Primary– Secondary• Blood circuitryStem CellsES cellsMesodermHemangioblastsCardiovascular progenitor cellsEndothelial Progenitor cellsCardiomyocytesHematopoieticProgenitor cellsVascular progenitor cellsSmooth muscle Cells (Pericytes)Blood vesselsCD38-CD34-c-kit+CD133+CD45+Oct 3/4+Sox2+CD 31+, CD34+, VE-Cad, vWF, eNOSCD133+, CD34+/-CD31+, CD45-c-kit+ Flk-1+ (VEGFR2+)Early embryoBlastocyst stageInner cell mass containing ES cellsStem cellsare removedEndodermLungsMucosal liningLiverEctodermSkinNerveseyesKit*+, SCA1+, SP or MDR1+(NKX2-5+ or Isl1+)CD45+ and CD133+(PROM1)Bone Marrow-Derived Hematopoietic Stem CellsComponents of the Blood:Plasma• Component of blood that is free of blood cells• Can be obtained by centrifugation• Makes up ~55% of the blood volume• Slightly alkaline fluid with pale yellowish color• Approximately 90 % water and 10% dry matter (dissolved)• Ninety percent organic substances, 10% minerals• Serum: plasma with clotting factors removedComponents of the Blood:Blood CellsIdentifying cell types in the bloodErythrocytes: Red Blood Cells• Rich in hemoglobin, a protein able to loosely bind oxygen• Responsible for providing oxygen to tissues• Partly responsible for recovering carbon dioxide produced as waste• Features that make erythrocytes more efficient for transport/diffusion of oxygen:– Lack of nucleus allows more room for hemoglobin– Biconcave shape of cells raises surface area to cytoplasmic volume ratio• Under shear stress, can release ATP and nitric oxide to cause dilation of blood vessels and promote normal blood flow• Mean lifespan: 100-120 days• Approximately 7 μm in diameter• Density in the blood: 4.5 million – 6 million cells/mm3(greater for men vs. women)• Hematocrit: percent volume of red blood cells in blood (men: 45%, women: 40%)• At end of life, retained by spleen and undergo phagocytosis by macrophagesOxygen Affinity of HemoglobinPlatelets,Thrombocytes• Small disk-shaped cell fragments (no nucleus)• Main function: stop loss of blood from wound (hemostasis)• When aggregated, platelets release factors that promote blood coagulation– Serotonin reduces diameter of lesioned vessels, reducing blood loss– Fibrinogen converted to active form, fibrin, by thrombin; trap cells and make clot• Approximately 2-3 µm in diameter • Density in the blood: 130,000 – 360,000 platelets/mm3Platelets are not true cells: - They germinate from large leukocytes called megakaryocytes- They are small sized diskettes about 3 µm in diameter- When stained, they appear a purple color and are more intense than red cellsLeukocytes:White Blood Cells• Responsible for defense of the organism• Density in the blood: 4,000 – 10,000/mm3 (much less numerous than red blood cells)• Divide into two categories: – Granulocytes: defined by presence of granules in the cytoplasm• Granules are different and help to distinguish different cell types• Granules have different affinities for neutral, acidic or basic stains: neutrophil, eosinophil (acidophil), basophil– Lymphoid cells (agranulocytes): no granules in cytoplasm• Lymphocyte• Monocyte• Each type of leukocyte is present in the blood in different proportions:– Neutrophil: 50 – 70%– Eosinophil: 2 – 4%– Basophil: 0.5 – 1%– Lymphocyte: 20 – 30%– Monocyte: 3 – 8%• Very active in phagocytosis of bacteria• Present in large amount in the pus of wounds• Not able to renew the lysosomes used in digesting microbes; die after having phagocytosed a few microbes• Approximately 12-15 µm in diameter• Recognizable because nucleus is divided into 2 to 5 lobes connected by a fine nuclear strand or filament• Immature neutrophils have band-shaped or horseshoe-shaped nucleus; known as band cellsNeutrophils• Attack parasites and phagocyte antigen-antibody complexes• Cytoplasm is full of granules which assume a characteristic pink-orange color when stained Eosinophils(Acidophils)• Secrete anti-coagulant and vasodilatory substances such as histamines and serotonin (serotonin can have vasoconstrictive or vasodilatory effects, depending on the scenario) • Have a phagocytic capability, but main function is secreting substances which mediate the hypersensitivity reaction • Rarest leukocytes: less than 1 % • Approximately 9-10 µm in diameter • Cytoplasm very rich in granules which take on a dark purple color when stained• Nucleus is bi- or tri-lobed, but is hard to see because large number of granules hide it Basophils• Present in blood, lymphoid tissues and organs, and lymph circulating in the lymphatic vessels• Lymphoid organs include: thymus, bone marrow, spleen, lymphoid nodules (lymph nodes), palatine tonsils, Peyer’s patches, lymphoid tissue of respiratory and GI tracts• Most circulate in blood in resting state• Slightly larger than red blood cells (approximately 8-10 µm in diameter)• Have compact, round nucleus which occupies nearly all cellular volume; cytoplasm is very reduced• Based on quantity of cytoplasm, lymphocytes are divided into small, medium and large categories• In lymphoid tissues and organs: can be activated to differing degrees following antigenic stimulation• In blood: lymphocytes are 20-30 % of all leukocytesLymphocytes• Each lymphocyte recognizes only a specific, complementary antigen• Large number of circulating lymphocytes allows for recognition of practically all substances in organism (both foreign and its own); together, able to recognize hundreds of millions or even billions of different molecules• Auto-immunity controlled in part by regulator T-cells (also called suppressor cells)• When activated, cooperate among themselves to amplify and increase precision of immune response • Two types of lymphocytes: T and B lymphocytesLymphocytesB Lymphocytes• Produced in the bone marrow• Each B cell has a specific antibody as cell-surface receptors• When antibodies on surface of B cell meet their specific complementary epitope on an antigen, antibodies bind epitope and hold antigen to cell• Binding of cell-surface antibody to its target antigen activates B cell, triggering rapid cloning/replication of that B cell (clonal selection, usually with aid of helper T-cells) • Clonal selection