A&P II Chap 19 Notes PDF - Blood cells, properties, formation, clotting, factors, stem cells, groups and PDF

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Blood cells, properties, formation, clotting, factors, stem cells, groups and typing...

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Anatomy & Physiology II! Chapter 19 Notes" Functions and Properties of Blood -Cardiovascular system consists of blood, heart and blood vessels " -Hematology: study of blood " -Blood: liquid connective tissue that consists of cells surrounded by a liquid extracellular matrix called blood plasma " -Interstitial Fluid: fluid that bathes the body cells and is constantly renewed by the blood " -Functions of the blood:" # -Transportation: transports oxygen from the lungs to the cells of the body and carbon dioxide from the body cells to the lungs for exhalation " # # -Carries nutrients from GI tract to body cells and hormones from endocrine glands to other body cells " # -Regulation: helps maintain homeostasis of all body fluids " # # -Regulates pH through the use of buffers " # # -Helps adjust body temperature " # # -Blood osmotic pressure influences the water content of cells " # -Protection: clotting " # # -WBCs protect against disease " # # -Blood proteins including antibodies help protect against disease " -Physical Characteristics:# " # -Denser and more viscous (thicker) than water and feels slightly sticky " # -38°C (100.4°F)" # -Slightly alkaline pH ranging from 7.35-7.45" # -When saturated with O₂, it is bright red, when unsaturated it is dark red " # -Blood volume in average male is 5-6L" # -Blood volume in average female is 4-5L" -Components of blood:# " # -Whole blood has two components: blood plasma and formed blood (cells and cell fragments) " # -About 45% formed elements, 55% plasma" # -Buffy Coat: pale, colorless WBCs and platelets occupy less than 1% formed elements " -Blood Plasma" # -91.5% water, 8.5% solutes (proteins)" # -Plasma proteins " # -Hepatocytes synthesize most of the plasma proteins called albumins, globulins, and fibrinogen " # # -Antibodies (immunoglobulins) are also plasma proteins " -Formed Elements:" # -RBCs, WBCs, platelets (erythrocytes, leukocytes)" # -Types of WBCs:" # # -Neutrophils, basophils, eosinophils, monocytes, lymphocytes (T cells, B cells, natural killer)" # -Platelets: fragments of cells that do not have a nucleus " # # -Release chemicals that promote clotting when blood vessels are damaged " # -Hematocrit: % of total blood volume occupied by RBCs" # # -Normal range for adult female: 38-46%" # # -Normal range for adult male: 40-54%" # # # -Testosterone stimulates synthesis of erythropoietin (EPO), the hormone that in turn stimulates production of RBCs, therefore testosterone contributes to higher hematocrit in males" # -Polycythemia: percentage of RBC is abnormally high (hematocrit of 65%↑)"

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# -Caused by dehydration, use of EPO by athletes" -Anemia: lower than normal number of RBCs"

Formation of Blood Cells -Most formed elements of the blood last only hours, days, or weeks and must be replaced regularly " -The abundance of the different types of WBCs varies in response to challenges by invading pathogens and other foreign antigens " -Hemopoiesis: process by which the formed elements of the blood develop " # -First occurs in yolk sac of embryo and later in liver, spleen, thymus, and lymph nodes of fetus " # -Red bone marrow becomes the primary site of hemopoiesis for life (last 3 months in womb)" -Red Bone Marrow: highly vascularized connective tissue located in microscopic spaces between trabeculae of spongy bone tissue " # -In bones of axial skeleton, pectoral and pelvic girdles, and the proximal epiphyses of the humerus and femur " # -0.05-0.1% of RBM cells are pluripotent stem cells " # # -Have capacity to develop into many different types of cells " # -As an individual ages, RBM becomes inactive and is replaced by yellow bone marrow (fat)" # -Under certain conditions (ex. severe bleeding) YBM can revert back to RBM " # -Stem cells in RBM reproduce themselves, proliferate, and differentiate into cells that give rise to blood cells, macrophages, reticular cells, mast cells, and adipocytes " -Pluripotent stem cells produce two further types of stem cells:" # -Myeloid Stem Cells: give rise to RBCs, platelets, monocytes, neutrophils, eosinophils, basophils, and mast cells " # -Lymphoid Stem Cells: give rise to lymphocytes and natural killer (NK) cells " # -The various stem cells resemble lymphocytes " -Some of the myeloid stem cells differentiate into progenitor cells and others develop directly into precursor cells " # -Progenitor cells are no longer capable of reproducing themselves and are committed to giving rise to more specific elements of blood " # # -Colony forming units (CFUs)" # # -Like stem cells, resemble lymphocytes and cannot be distinguished by their microscopic appearance alone " # -Precursor Cells (blasts): over several cell divisions they develop into the actual formed elements of blood and have recognizable microscopic appearances " -Hemopoietic Growth Factors: regulate the differentiation and proliferation of particular progenitor cells" -Erythropoietin (EPO): increases number of RBC precursors " # -Produced primarily by cells in the kidneys " -Thrombopoietin (TPO): hormone produced by liver that stimulates formation of platelets from megakaryocytes" -Cytokines: small glycoproteins that are typically produced by cels such as RBM, leukocytes, macrophages, fibroblasts, and endothelial cells " # -Generally act as local hormones " # -Regulate development of different blood cell types " # -Stimulate proliferation of progenitor cells " # -Regulate activities of cells involved in non specific defenses and immune responses " # -Cytokines that stimulate WBC formation:" # # -Colony stimulating factors (CSFs)" # # -Interleukins "

Red Blood Cells -Erythrocytes" -Hemoglobin: oxygen carrying protein; gives whole blood its red color " -Adult male ~5.4% million RBCs per μl" -Adult female ~4.8% million RBCs per μl" -New mature cells must enter the circulation at a rate of at least 2 million per second to balance the equally high rate of RBC destruction " -Biconcave discs" -Certain glycolipids in plasma membrane are antigens that account for various blood groups such as ABO and Rh groups " -Lack a nucleus and other organelles and can neither reproduce nor carry on extensive metabolic activities " -Highly specialized for their oxygen transport function" -Generate ATP anaerobically so they do not use up any of the oxygen they transport " -Each RBC contains about 280 million hemoglobin in molecules " -Globin: hemoglobin protein composed of 4 polypeptide chains; a ringlike nonprotein pigment called cheme is bound to each of the four chains; at the center of each heme ring is an iron ion (Fe²⁺) that can combine reversibly with one O₂ molecule -Each O₂ picked up from the lungs is bound to an Fe²⁺. As blood flows through tissue capillaries, the iron-oxygen reaction reverses -Hemoglobin also transports about 23% of the total carbon dioxide -Hemoglobin also plays a role in regulation of blood flow and BP -Nitric Oxide (NO) produced by the endothelial cells that line the blood vessels, binds to hemoglobin -Under certain circumstances, hemoglobin releases NO -The release of NO causes vasodilation -Live only about 120 days -Recycling of RBCs occurs as follows: -Macrophages in spleen, liver, or RBM phagocytize ruptured and worn out RBCs -Globin and heme portions of hemoglobin are split -Globin is broken down into amino acids, which can be reused to synthesize other proteins -Iron is removed from the heme and associates with the plasma protein transferrin (a transporter for Fe³⁺ in the bloodstream) -In muscle fibers, liver cells, and macrophages of the spleen and liver, Fe³⁺ detaches from transferrin and attaches to an iron-storage protein called ferritin -On release from a storage site or absorption from GI tract, Fe³⁺ reattaches to transferrin -The Fe³⁺-transferrin complex is then carried to RBM where RBC precursor cells take it up through receptor-mediated endocytosis for use in hemoglobin synthesis -Iron is needed for the heme portion of hemoglobin and amino acids are needed for the globin -Vitamin B₁₂ is also needed for synthesis of hemoglobin -Erythropoiesis in RBM results in production of RBCs, which enter the circulation -When iron is removed from heme, the non-iron portion of heme is converted to biliverdin (green pigment) then into bilirubin (yellow-orange pigment) -Bilirubin enters bloodstream and is transported to the liver -In the liver, bilirubin is released by liver cells into bile, which passes into the small intestine and then into the large intestine -In the large intestine, bacteria convert bilirubin into urobilinogen

-Some urobilinogen is absorbed back into the blood, converted to a yellow pigment, urobilin, and excreted in urine -Most urobilinogen is eliminated in feces in the form of a brown pigment called stercobilin Erythropoiesis -Production of RBCs -Starts in RBM with a precursor cell called a proerythroblast -Divides several times, producing cells that begin to synthesize hemoglobin -Ultimately, a cell near the end of the development sequence ejects its nucleus and becomes a reticulocyte -Loss of the nucleus causes the center of the cell to indent -Reticulocytes retain some mitochondria, ribosomes, and endoplasmic reticulum -They pass from RBM into the bloodstream by squeezing between plasma membranes of adjacent endothelial cells of blood capillaries -Develop into mature RBCs within 1-2 days after their release from RBM -Normally, erythropoiesis and RBC destruction proceed at roughly the same pace -Hypoxia: oxygen deficiency at the tissue level -May occur if too little oxygen enters the blood -High altitudes -Anemia -Stimulates kidneys to step up the release of erythropoietin, which speeds the development of proerythroblasts into reticulocytes in the red bone marrow -Blood Doping: ahtletes increase their RBC count because increasing the oxygen in the blood increases athletic performance (artificially induced polycythemia: abnormally high # of RBCs) -Natural Blood Doping: altitude training greatly improves fitness, endurance, and performance -At higher altitudes, the body increases the production of RBCs, which means that exercise greatly oxygenates the blood White Blood Cells (Leukocytes) -Have nuclei and a full complement of other organelles -Do not contain hemoglobin -Classified as either granular or agranular, depending on whether they contain conspicuous chemical filled cytoplasmic granules (vesicles) -Granular Leukocytes -Neutrophil: granules are smaller than those of other granular leukocytes, evenly distributed, and pale lilac -Nucleus has 2-5 lobes, develops more with age -Eosinophil: large, uniform-sized granules -Granules usually do not cover or obscure the nucleus which often has 2 lobes -Basophil: round, variable-sized granules that stain blue-purple -Granules commonly obscure nucleus which has 2 lobes -Agranular Leukocytes -Lymphocytes: nucleus stains dark and is round or slightly indented -Cytoplasm stains sky blue and forms a rim around the nucleus -Monocyte: nucleus is kidney or horseshoe shaped and cytoplasm is blue-gray and has a foamy appearance -Azurophilic Granules: lysosomes -Migrate from blood into tissues, where they enlarge and differentiate into macrophages

-Some become fixed (tissue) macrophages meaning they reside in a particular tissue -Others become wandering macrophages which roam tissues and gather at sites of infection or inflammation -WBCs and all other nucleated cells in the body have proteins, major histocompatibility (MHC) antigens protruding from their memories into the ECF (cell identity marker) -In a healthy body, some WBCs, especially lymphocytes, can live for months or years, but most live only a few days -Far less numerous than RBCs (5000-10,000/μl) -Leukocytosis: increase in number of WBCs above 10,000 μl, is a normal, protective response to stresses (ex. invading microbes, surgery) -Leukopenia: abnormally low level of WBCs, below 5,000 μl (ex. chemo, radiation) -Once pathogens enter the body, the general function of WBCs is to combat them by phagocytosis -WBCs leave the bloodstream and collect at sights of pathogen invasion or inflammation -Once granular leukocytes and monocytes leave the bloodstream to fight injury or infection, they don’t return to it -Lymphocytes continually recirculate from blood to interstitial spaces of tissues to lymphatic fluid and back to blood -WBCs leave the bloodstream by emigration (diapedesis) in which they roll along the endothelium, stick to it, and then squeeze between endothelial cells -Adhesion molecules help WBCs stick to the endothelium -Neutrophils and macrophages are active in phagocytosis: ingest bacteria and dispose of dead matter -Chemotaxis: several different chemicals released by microbes and inflamed tissues attract phagocytes -Neutrophils respond most quickly to tissue destruction by bacteria -After engulfing a pathogen during phagocytosis, a neutrophil unleashes several chemicals to destroy the pathogen -Lysozyme: destroys certain bacteria -Strong oxidants -Neutrophils also contain defensins, proteins that exhibit a broad range of antibiotic activity against bacteria and fungi -Eosinophils leave capillaries and enter tissue fluid -Believed to release enzymes, such as histaminase, that combat the effects of histamine and other substances involved in inflammation during allergic reactions -Also phagocytize antigen-antibody complexes are effective against certain parasitic worms -At sites of inflammation, basophils leave capillaries, enter tissues, and release granules that contain heparin, histamine, and serotonin -These intensify the inflammatory reaction and are involved in hypersensitivity (allergic) reactions -Like basophils, mast cells release substances involved in inflammation including heparin, histamine, and proteases -Mast cells are widely dispersed in the body -Lymphocytes: B cells, T cells, and natural killers (NK) -B cells are particularly effective in destroying bacteria and inactivating their toxins -T cells attack infected body cells and tumor cells and are responsible for the rejection of transplanted organs

-Immune responses carried out by both B and T cells help combat infection and provide protection against some diseases -Natural Killer cells attack a wide variety of infected body cells and certain tumor cells -Monocytes take longer to reach a site of infection than neutrophils, but they arrive in larger numbers and destroy more microbes -Upon arrival, enlarge and differentiate into wandering macrophages which clean up cellular debris and microbes by phagocytosis after an infection -An increase in number of circulating WBCs usually indicate inflammation or infection -Differential white cell count Platelets -Hemopoietic stem cells also differentiate into cells that produce platelets -With thrombopoietin, myeloid stem cells develop into megakaryocyte colony-forming cells that in turn develop into precursor cells called megakaryoblasts -Megakaryoblasts transform into megakaryocytes, huge cells that splinter into 2-3000 fragments each of which becomes a platelet -Between 150,000-400,000 platelets are present in each microliter of blood -Have many vesicles but no nucleus -Their granules contain chemicals that promote blood clotting when released Stem Cell Transplants -Bone Marrow Transplant: replacement of cancerous or abnormal RBM with healthy RBM in order to establish normal blood cell counts -Defective RBM is destroyed by high does of chemotherapy and whole body radiation just before the transplant takes place -This kills cancer cells and destroys the patient’s immune system in order to decrease the chance of transplant rejection -RBM from a donor is usually removed from the iliac crest and then injected into the recipient’s vein -The injected marrow migrates to the RBM cavities, where the donor’s stem cells multiply -Used to treat aplastic anemia, Hodgkin’s Disease, breast cancer -It takes 2-3 weeks for transplanted bone marrow to produce enough WBCs to protect against infection -Transplanted RBM may produce T cells that attack the recipient’s tissue: graft-versushost disease -Any of the recipient’s T cells that survived the chemo/radiation can attack donor cells -Patient must take immunosuppressant drugs for life -Cord Blood Transplant: stem cells may be obtained from the umbilical cord shortly after birth -Removed from cord with syringe the frozen -This has several advantages over RBM: -Easily collected -More abundant -Less likely to cause graft-vs-host -Less likely to transmit infections -Can be stored indefinitely Hemostasis -Sequence of responses that stop bleeding

-Vascular Spasm: when arteries or arterioles are damaged, the circularly arranged smooth muscle in their walls contracts immediately -Reduces blood loss for several minutes to several hours -Probably caused by damage to smooth muscle, by substances released from activated platelets, and by reflexes initiated by pain receptors -Platelet Plug Formation: with many vesicles are clotting factors: AOP, ATP, Ca²⁺, 5HT -Also present are enzymes that produce thromboxane A2 (a prostaglandin), fibrinstabilizing factor (helps to strengthen blood clot), lysosomes, mitochondria, and glycogen -Platelet Derived Growth Factor (PDGF): a hormone that can cause proliferation of vascular endothelial cells, vascular smooth muscle fibers, and fibroblasts to help repair damaged blood vessel walls -Occurs as follows: -Platelets contact and stick to parts of a damaged blood vessel (platelet adhesion) -Platelets become activated, they extend many projections that enable them to contact and interact with one another, and they begin to liberate the contents of their vesicles (platelet, release reaction) -Liberated ADP and thromboxane A2 activate nearby platelets -5-HT and thromboxane A2 function as vasoconstrictors which decreases blood flow through the injured vessel -Release of ADP makes other platelets in the area sticky causing the newly recruited and activated platelets to adhere to the originally activated platelets (platelet aggregation) -Platelet Plug: accumulation and attachment of large numbers of platelets form a mass -Very effective in preventing blood loss in a small vessel Blood Clotting -If blood is drawn from the body, its thickens and forms a gel which eventually separates from the liquid -Serum: blood plasma minus the clotting proteins -Blood Clot: gel -Clotting (Coagulation): process of gel formation -Series of chemical reactions that culminates in formation of fibrin threads -Thrombosis: clotting in an undamaged vessel; if blood clots to easily -Clotting factors: Ca²⁺, several inactive enzymes that are synthesized by hepatocytes and released into the bloodstream, various molecules associated with platelets or released by damaged tissues -Clotting is a complex cascade of enzymatic reactions in which each clotting factor activates many molecules of the next one in a fixed sequence -Clotting can be divided in three stages: -Two pathways, extrinsic and intrinsic, lead to the formation of prothrombinase -Once prothrombinase is formed, the steps involved in the next two stages of clotting are the same for both pathways which become the common pathway -Prothrombinase converts prothrombin into the enzyme thrombin -Thrombin converts soluble fibrinogen into insoluble fibrin which forms the threads of the clot -The Extrinsic Pathway: occurs rapidly, within a matter of seconds if trauma is severe

-Tissue Factor (TF or thromboplastin): leaks into the blood from cells outside blood vessels and initiates the formation of prothrombinase -TF is a complex mixture of lipoproteins and phospholipids released from the surfaces of damaged cells -In the presence of Ca²⁺, TF begins a sequence of reactions that ultimately activates clotting factor X -Once factor X is activated, it combines with factor V in the presence of Ca²⁺ to form the active enzyme prothrombinase -The Intrinsic Pathway: more complex, occurs more slowly — usually requiring several minutes -Its activators are either in direct contact with blood or contained within the blood -Outside tissue damage is not needed -If endothelial cells become roughened or damaged, blood can come in contact with collagen fibers in the connective tissue around the endothelium of the blood vessel -Trauma to endothelial cells causes damage to platelets, resulting in the release of phospholipids by the platelets -Contact with collagen fibers activates clotting fa...