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Transport Protection O2, CO2, nutrients, wastes, hormones, and heat Platelets & clotting WBCs: Immunity & Inflammation Regulation “Chemistry” pH & buffering of ECF & blood “Amount” Fluid and electrolyte balance You have about 4-6 liters of blood (think 5!) ≈ 8% of total body weight 100.4 degrees F Plasma =clear extracellular fluid (& mostly water) “Cells” float in the plasma Erythrocytes Leukocytes Platelets Viscosity = resistance to flow whole blood ≈ 5 times as viscous as H2O Osmolarity = has to do with # of dissolved particles (see p. 104-105 for review) total number of dissolved particles in the blood is important! sodium ions, protein (albumins) & RBCs = most important affectors of blood osmolarity Molarity = # of moles (of substance) per liter of solution Osmolarity = # of osmoles per liter of solution WHAT?! e.g. 1 osmole = 1 mole of dissolved PARTICLES (not necessarily = to the number of moles of the SUBSTANCE you put in!) Depends on whether the substance is IONICALLY bonded or COVALENTLY bonded 1 Mole glucose 1 osm glucose solution BUT: 1 Mole NaCl 2 osm Na+ + Cl- solution (NaCl disassociates in solution to twice the number of particles) TAKE HOME MESSAGE: The total number of particles in blood vs. ECF is important! Water will move into compartment with more particles (think, “to try to disperse them” and balance osmolarity). Therefore: Balance between Blood and ECF depends on: Ignore details of picture for now - just get main idea, that osmolarity is really IMPORTANT and helps govern which way fluid will move! 1) Filtration OUT of capillary -Pressure, viscosity & osmolarity 2) Reabsorption by OSMOSIS High blood osmolarity: causes fluid absorption into blood (from gut & ECF) = raises BP Low blood osmolarity: causes fluid to remain in tissues = lowers BP, may result in edema Plasma – liquid “matrix” (of vascular connective tissue) Serum remains after plasma clots 3 major categories of plasma proteins albumins - most abundant contributes to viscosity and osmolarity globulins (antibodies) provide immune system functions alpha, beta and gamma globulins fibrinogen precursor of fibrin threads that help form blood clots Plasma proteins formed by liver except globulins (produced by plasma cells=transformed B lymphocytes in connective tissues) Colloid Osmotic Pressure: is the contribution of proteins to the osmolarity of blood Plasma Protein Deficiency: -liver disease or -starvation Changes Body Osmolarity Balance! Kwashiorkor Example: Canabalize tissues muscle wasting Low Protein Diet low protein levels in body low blood osmolarity Fluid buildup in tissues & ascites Nitrogenous compounds Nutrients amino acids from dietary protein or tissue breakdown nitrogenous wastes (urea) toxic end products of catabolism normally removed by the kidneys glucose, vitamins, fats, minerals, etc O2 and CO2 Electrolytes Na+ makes up 90% of plasma cations BUN Creatinine Iron (animation is the next “slide” – just know terms below!) Ferric (Fe3+) vs Ferrous (Fe2+) stomach acid converts Fe3+ to absorbable Fe2+ Binds to THREE different proteins: Vitamin B12 and Folic Acid Gastroferritin – in stomach Transferrin – in bloodstream Apoferritin + Fe2+ = Ferritin (stored in liver) Iron used in: bone marrow for hemoglobin, muscle for myoglobin and all cells use for cytochromes in mitochondria rapid cell division Vitamin C and Copper cofactors for enzymes synthesizing RBCs Hemopoietic tissues produce blood cells yolk sac produces stem cells liver stops producing blood cells at birth spleen remains involved with WBC production red bone marrow pluripotent stem cells hemopoiesis produces RBCs, WBCs and platelets Biconcave cells 7.5 M diameter Blood type determined by surface glycoprotein and glycolipids Cytoskeletal proteins (spectrin & actin) give membrane durability, but wear out ≈ 4 months No mitochondria = anerobic respiration Eject nucleus so must make all proteins in advance Spleen = RBC “graveyard” ≈ 2.5 million released into circulation every second! 18-27 Gas transport - major function increased surface area/volume ratio due to loss of organelles during maturation increases diffusion rate of substances 33% of cytoplasm is hemoglobin (Hb) O2 delivery to tissue and CO2 transport to lungs Carbonic anhydrase (CAH) produces carbonic acid from CO2 and water important role in gas transport and pH balance Carry oxygen from the lungs to your tissues (& some CO2 from tissues to lungs) Contain hemoglobin, a protein molecule that actually carries the O2 Heme groups conjugate with each protein chain hemoglobin molecule can carry four O2 oxygen binds to central ferrous ion (Fe2+) Globins - 4 protein chains 2 alpha and 2 beta chains Except in fetus (HbF) gamma chains replace beta chains; whole thing binds O2 better = due to switching over from Fetal Hemoglobin (HbF) to Adult Hemoglobin (HbA) after birth = increased hemolysis of fetal RBCs causes increase in blood levels of bilirubin! (We’ll talk about the advantages and disadvantages of Fetal Hemoglobin in the next unit - just know the above for now!) “RBC count” and “hemoglobin concentration” indicate amount of O2 blood can carry hematocrit (packed cell volume) = % of blood composed of cells (think ≈ 45%) men 42- 52% cells; women 37- 48% cells hemoglobin concentration of whole blood (think ≈ 15%) men 13-18g/dL; women 12-16g/dL RBC count (think ≈ 5 million per cm3 - that’s cubic centimeter) men 4.6-6.2 million/L; women 4-2-5.4 million/L Higher Lower This is what a hematocrit capillary tube looks like the person is measuring the hematocrit percentage. Negative feedback control: drop in RBC count causes hypoxia in tissues EPO production stimulates bone marrow RBC count in 3 - 4 days (count too high = polycythemia) Causes of Hypoxemia? low levels O2 (altitude) increase in exercise loss of lung tissue in emphysema 2.5 million RBCs/sec Development takes 3-5 days First committed cell - erythrocyte colony forming unit reduction in cell size, increase in cell number, synthesis of hemoglobin and loss of nucleus has receptors for erythropoietin (EPO) from kidneys! Erythroblasts multiply and synthesize hemoglobin Discard nucleus to form a reticulocyte named for fine network of endoplasmic reticulum 0.5 to 1.5% of circulating RBCs Iron removed from heme and converted (stepwise) into bilirubin Bilirubin is released into blood plasma (kidneys yellow urine = urochrome) liver secretes into bile concentrated in gall bladder: released into small intestine; bacteria create urobilinogen (brown feces) 18-36 Polycythemia - an excess of RBCs (excessive erythropoiesis) Always triggered by hypoxemia, no matter what the cause Primary Polycythemia Cancer of erythropoietic cell line in red bone marrow hematocrit as high as 80%!! Secondary Polycythemia (from hypoxemia) From dehydration, emphysema, high altitude, or physical conditioning Dangers of polycythemia increased blood volume, pressure, viscosity can lead to embolism, stroke or heart failure Anemia is a deficiency in O2 carrying-capacity of the blood! Due to: Low hemoglobin in the cells OR Too few RBCs Symptoms: Pallor Weakness Tiredness Unable to exercise without getting out of breath Inadequate erythropoiesis or hemoglobin synthesis inadequate vitamin B12 from poor nutrition or lack of intrinsic factor (pernicious anemia) Don’t iron-deficiency anemia make kidney failure and insufficient erythropoietin enough aplastic anemia - complete cessation of Hemorrhagic anemias Hemolytic anemias Lose cells faster than you can make them Tissue hypoxia and necrosis Low blood osmolarity (tissue edema) Low blood viscosity (heart races and pressure drops) Short of breath and lethargic Hereditary Hb ‘defect’ common in peoples of African descent Recessive allele modifies hemoglobin structure under low O2 conditions (hypoxemia) Due to a single amino acid substitution only! 1 in 500 African Americans have the disease 1 in 1000 to 1400 Hispanic-Americans Antigens unique molecules on cell surface used to distinguish self from foreign foreign antigens generate immune response Antibodies secreted by plasma cells as part of immune response to foreign matter Agglutination antibody molecule binding to antigens causes clumping RBC antigens =Branched sugars Or called agglutinogens (because they’re not antigenic to YOU, who made them) A and B on RBC surface Your ABO blood type is determined by presence or absence of antigens (agglutinogens) on RBCs type A person has A antigens (although they’re not antigenic to YOURself) type B person has B antigens type AB has both antigens type O has neither antigen most common - type O rarest - type AB Antibodies (agglutinins); anti-A and -B Appear 2-8 months after birth; at maximum concentration at 10 yr. Anti -A and/or -B (both or none) are in plasma you do not form antibodies against your antigens Agglutination each antibody can attach to several foreign antigens at the same time Responsible for mismatched transfusion reaction Agglutinated RBCs block blood vessels and hemolyze free Hb blocks kidney tubules, causes death Universal donor Type O lacks antigenic branched sugar on RBC surface donor’s plasma may have antibodies against recipient’s RBCs, however … (but transfused volume is smaller than amount of blood in recipient’s body - hopefully) may give packed cells (minimal plasma) Universal recipient Type AB lacks plasma antibodies; no anti- A or B Rh (D) agglutinogens discovered in rhesus monkey in 1940 Rh+ blood type has D agglutinogens on RBCs Rh frequencies vary among ethnic groups Anti-D agglutinins not normally present form in Rh- individuals exposed to Rh+ blood Rh- woman with an Rh+ fetus or transfusion of Rh+ blood no problems with first transfusion or pregnancy Occurs if mother has formed antibodies and is pregnant with 2nd Rh+ child Anti-D antibodies can cross placenta Prevention RhoGAM given to pregnant Rh- women binds fetal agglutinogens in her blood so she will not form Anti-D antibodies Fig. 18.16 Rh antibodies attack fetal blood causing severe anemia and toxic brain syndrome 5,000 to 10,000 WBCs/L Conspicuous nucleus Travel in blood before migrating to connective tissue Protect against pathogens (We’ll talk more about WBCs in Lymphatic System & Immunity lecture) Neutrophils ( in bacterial infections) phagocytosis of bacteria release antimicrobial chemicals Eosinophils ( in parasitic infections or allergies) phagocytosis of antigen-antibody complexes, allergens and inflammatory chemicals release enzymes to destroy parasites Basophils ( in chicken pox, sinusitis, diabetes) secrete histamine (vasodilator) secrete heparin (anticoagulant) Lymphocytes ( in diverse infections and immune responses) destroy cells (cancer, foreign, and virally infected cells) “present” antigens to activate other immune cells coordinate actions of other immune cells secrete antibodies and provide immune memory Monocytes ( in viral infections and inflammation) differentiate into macrophages phagocytize pathogens and debris “present” antigens to activate other immune cells These things are usually included: Hematocrit Hemoglobin concentration Total count for RBCs, reticulocytes, WBCs, and platelets Differential WBC count RBC size and hemoglobin concentration per RBC Leukopoiesis Colony-forming units in each cell line (in bone marrow) T lymphocytes complete development in thymus Red bone marrow stores and releases granulocytes and monocytes Circulating WBCs do not stay in bloodstream granulocytes leave in 8 hours and live 5 days longer monocytes leave in 20 hours, transform into macrophages and live for several years WBCs provide long-term immunity (decades) Fig. 18.18 Leukopenia = low WBC count (<5000/L) causes: radiation, poisons, infectious disease effects: elevated risk of infection Leukocytosis = high WBC count (>10,000/L) causes: infection, allergy and disease differential count - distinguishes % of each cell type Leukemia = cancer of hemopoietic tissue Actually causes a HIGH WBC count, but cells are immature and not able to perform proper functions So it is AS IF you had far too few WBCs! acute and chronic - death in months or 3 years effects - normal cell % disrupted; impaired clotting Platelets Fibrinogen Compare: small Lymphocyte Erythrocyte Platelet Small fragments of megakaryocytes 2-4 m diameter; contain “granules” amoeboid movement and phagocytosis Functions secrete vasoconstrictors stick together to form temporary platelet plugs secrete clotting factors initiate formation of clot-dissolving enzyme chemically attract neutrophils and monocytes to sites of inflammation phagocytize bacteria All 3 steps involve platelets Pain receptors through reflex arc, cause constriction of vessel Smooth muscle injury Platelets release serotonin (=vasoconstrictor) Normally endothelium = smooth Broken vessel exposes rough collagen Platelet pseudopods STICK to rough collagen and other platelets Pseudopods contract and draw walls of vessel together forming a platelet plug 18-64 GOAL = to convert Fibrinogen to Fibrin Threads Fibrinogen (a plasma protein) is converted into fibrin threads which form the clot TWO DIFFERENT ways this can be initiated: Clotting factors coming from within the blood itself OR Clotting factors from vessel wall 18-65 GOAL of BOTH pathways to make Fibrin Threads by activating Fibrinogen Two DIFFERENT ways to get to Factor X (‘weird’, but handy) Extrinsic pathway Clotting factors come from OUTSIDE the blood itself Initiated by damaged tissues Fewer steps to Factor X, so takes about 15 seconds Intrinsic pathway Clotting factors all found IN the blood Initiated by platelets More steps, so takes 3-6 minutes! Some books have ERROR Calcium required for either pathway! Factor X gets activated by either pathway (intrinsic or extrinsic) Factor X activates something…. … that activates the ‘FINAL ACTIVATOR’ Thrombin Thrombin causes Fibrin threads to form by activating Fibrinogen Then they form 3-D mesh throughout platelet plug, entrapping RBCs, WBCs etc. ERROR Most of the clotting factors are made in the liver Liver diseases compromise clotting! Platelet-derived growth factor secreted by platelets and endothelial cells repair damaged vessel Fibrinolysis (dissolution of a clot) plasmin, a fibrin-dissolving enzyme (clot buster) Genetic lack of any clotting factor affects coagulation Sex-linked recessive (on X chromosome) Physical exertion causes bleeding and excruciating pain 18-70 transfusion of plasma or purified clotting factors factor VIII produced by transgenic bacteria Embolism - clot traveling in a vessel Thrombosis - abnormal clotting in unbroken vessel most likely to occur in leg veins of inactive people pulmonary embolism - clot may break free, travel from veins to lungs Infarction may occur if clot blocks blood supply to an organ (MI or stroke) 18-71 650,000 Americans die annually of thromboembolism Next – A Bit About Blood Vessels Arteries carry blood away from heart Veins carry blood back toward heart Capillaries connect smallest arteries to veins Tunica interna (intima) = smooth inner layer of simple squamous endothelium; with Internal elastic lamina (frequently seen) Tunica media = middle layer, usually thickest; smooth muscle, collagen, some elastic fibers woven among cells sometimes Tunica externa (or tunica adventitia) = outermost layer of loose connective tissue with vasa vasorum in larger arteries Arterioles (= resistance vessels) control amount of blood to various organs, by dilating or constricting Innervated by Sympathetic neurons Systemic body arterioles partially constricted at all times normally to maintain blood pressure! Metarterioles short vessels connect arterioles to venules through capillary beds Have smooth muscle cells that form precapillary sphincters around entrance to each capillary 1. Continuous - occur in most tissues endothelial cells have tight junctions with intercellular clefts (allow passage of solutes) 2. Fenestrated - kidneys, small intestine organs that require rapid absorption or filtration filtration pores – spanned by very thin glycoprotein layer allows passage of only small molecules 3. Sinusoids – liver, spleen, bone marrow irregular blood-filled spaces; some have extra large fenestrations, allow proteins and blood cells to enter Sinus rhythm – 70-80 BPM (beats per minute) w/Vagal innervation, called Vagal Tone SA node intrinsic rate = 100 BPM Ectopic focus – any region of spontaneous firing that is not SA So Vagus innervation SLOWS intrinsic heart rate! nodal rhythm - set by AV node, 40 to 50 bpm intrinsic ventricular rhythm - 20 to 40 bpm Arrhythmia - abnormal cardiac rhythm heart block: failure of conduction system bundle branch block total heart block (damage to AV node) Angina pectoris partial obstruction of coronary blood flow can cause chest pain pain caused by ischemia, often activity dependent Myocardial infarction complete obstruction causes death of cardiac cells in affected area pain or pressure in chest that often radiates down left arm Short, branched cells, one central nucleus Intercalated discs join myocytes end to end interdigitating folds - surface area mechanical junctions tightly join myocytes: fascia adherens: actin anchored to plasma membrane; transmembrane proteins link cells desmosomes electrical junctions - gap junctions allow ions to flow