Lecture: Physiology Of Blood
Lecture: Physiology of BloodI.Components, Characteristics, Functions of BloodA.Major Components of Blood1. formed elements - the actual cellular components of blood (specialconnective tissue)a.b.c.clottingerythrocytes - red blood cellsleukocytes - white blood cellsplatelets - cell fragments for2. blood plasma - complex non-cellularfluid surrounding formed elements; protein &electrolytesB. Separation of Components in aCentrifugeVOLUME1.2.3.clear/yellowish PLASMA55%thin/whitish buffy coat 1%with LEUKOCYTES & PLATELETSreddish mass - ERYTHROCYTES45%LAYERtopmiddlebottom
hematocrit - percentage by VOLUME of erythrocytes when blood is centrifuged(normal 45%)C.Characteristics of Blood1.2.3.4.5.6.7.8.D.bright red (oxygenated)dark red/purplish (unoxygenated)much more dense than pure waterpH range from 7.35 to 7.45 (slightly alkaline)slightly warmer than body temperature 100.4 Ftypical volume in adult male 5-6 literstypical volume in adult female 4-5 literstypically 8% of body weightMajor Functions of Blood1. Distribution & Transporta.b.oxygen from lungs to body cellscarbon dioxide from body cells to lungs
c.d.e.2.nutrients from GI tract to body cellsnitrogenous wastes from body cells to kidneyshormones from glands to body cellsRegulation (maintenance of homeostasis)a. maintenance of normal body pHi.blood proteins (albumin) & bicarbonateb. maintenance of circulatory/interstitial fluidi.electrolytes aid blood proteins (albumin)c. maintenance of temperature (blushed skin)3.Protectiona.b.platelets and proteins "seal" vessel damageprotection from foreign material & infectionsi. leukocytes, antibodies, complement proteins
II.Erythrocytes (red blood ells; RBCs)A.1.2.3.3.5.6.7.Structure7.5 micron diameter; 2.0 micron thickbiconcave disk shape; ideal for gas exchangei. spectrin - elastic protein; allows shape changemature cells are anucleate (no nucleus)very few organelles; mainly a hemoglobin carrieri. hemoglobin – 33% of cell mass; carries oxygenno mitochondria; only anaerobic respirationratio erythrocytes:leukocytes 800:1red blood cell count: # cells per cubic millimeteri. normal male count - 5.1 to 5.8 millionii. normal female count - 4.3 to 5.2 millionB. Functions (oxygen & carbon dioxidetransport)1.hemoglobin - large moleculeswith globin and hemesa.globin - complex proteinwith 4 polypeptides (2 alpha and 2 betapolypeptides)b.heme group - IRONcontaining pigment part of hemoglobin to which oxygenbindsi. each polypeptide has one heme group;each hemecarries one O2c. normal hemoglobin levels (grams/l00 ml blood)i.infants 14-20 grams/l00 mliiadult female 12-16 grams/100 ml
iii adult male 13-18 grams/l00 ml2.states of hemoglobina.oxyhemoglobin - when oxygen is bound to IRONb.deoxyhemoglobin - no oxygen bound to IRONc.carbaminohemoglobin - when carbon dioxide bound (topolypeptide chain)C.Hematopoiesis and Erythropoiesis1. hematopoiesis (hemopoiesis) - the maturation, development andformation of blood cellsa.red bone marrow (myeloid tissue) - location ofhematopoiesis; in blood sinusoids which connect withcapillaries; mainly in axial skeleton and heads of femur &humerusb.hemocytoblast (stem cell) - the mitotic precursor to bloodcells before differentiationi. differentiation - maturing cell becomes "committed" tobeing certain type blood cell2.erythropoiesis - the maturation, development, and formation ofRed Blood Cells (erythrocytes)hemocytoblast - proerythroblast - early (basophilic) erythroblast - late (polychromatophilic) erythroblast - (hemoglobin) normoblast - (nucleus ejected when enoughhemoglobin)reticulocyte - (retaining some endoplasmic reticulum)ERYTHROCYTE
hemocytoblast - reticulocytereticulocyte - ERYTHROCYTEERYTHROCYTE lifespan(primarily destroyed by macrophages in the spleen)3.3-5 DAYS2 DAYS (in blood)100-120 DAYSRegulation of Erythropoiesisa.hormonal controls - erythropoietin is the hormone thatstimulates RBC productionDECREASED oxygen level in blood causes KIDNEYS toincrease release of erythropoietin1.2.3.4.Less RBCs from bleedingLess RBCs from excess RBC destructionLow oxygen levels (high altitude, illness)Increased oxygen demand (exercise)Eythropoietin now genetically engineered and synthesized byAMGEN of Thousand Oaks.Testosterone can also mildly stimulate production of RBCs in humans
b.Iron - essential for hemoglobin to carry oxygeni.65% of Fe in body is in hemoglobinii. liver and spleen store most excess Fe bound toferritin and hemosideriniii. Fe in blood bound to transferriniv. daily Fe loss: 0.9 mg men/l.7 mg womenv.women also lose Fe during menstrual flowc.B-complex Vitamins - Vitamin B12 and Folic Acidessential for DNA synthesis in early mitotic divisions leading toerythrocytesD.Erythrocyte Disorders (Anemias & Polycythemias)1.Anemias - a symptom that results when blood has lower thannormal ability to carry oxygena.Insufficient erythrocyte counti.hemorrhagic anemia - loss of blood from bleeding(wound, ulcer, etc.)ii. hemolytic anemia - erythrocytes rupture(hemoglobin/transfusion problems, infection)iii. aplastic anemia - red marrow problems (cancertreatment, marrow disease, etc.)b.Decrease in Hemoglobini.iron-deficiency anemia - low Iron levels (diet;absorption, bleeding, etc.)ii. pernicious anemia - low Vitamin B12 (diet, intrinsicfactor for Vit B absorption)c.Abnormal Hemoglobin (usually genetic)i.thalassemia - easily ruptured RBCs (Greek & Italiangenetic link)ii. sickle-cell anemia - sickle-shaped RBCs (geneticAfrica, Asia, southern Europe link)2.Polycythemia - excess RBC count, causes thick blood
a.polycythemia vera - bone marrow problem; hematocritmay jump to 80%b.secondary polycythemia - high altitude (normal); or toomuch erythropoietin releasec.blood doping in athletes - RBCs previously withdrawn aretransfused before an event; more RBCs, more oxygen delivery to thebodyIII.Leukocytes (white blood cells; WBCs)A.General Structure and Function1.protection from microbes,parasites, toxins, cancer2.1% of blood volume; 4-11,000per cubic mm blood3.diapedesis - can "slip between"capillary wall4.amoeboid motion - movementthrough the body5.chemotaxis - moving in directionof a chemical6.leukocytosis - increased "whiteblood cell count" in response to bacterial/viral infection7.granulocytes - contain membrane-bound granules (neutrophils,eosinophils, basophils)8.agranulocytes - NO membrane-bound granules (lymphocytes,monocytes)
B. Granulocytes - granules in cytoplasm can be stained with Wright's Stain;bilobar nuclei; 10-14micron diameter; all are phagocytic cells (engulf material)1.neutrophils - destroy and ingest bacteria & fungi(polymorphonuclear leuks.; "polys")a.b.c.d.e.f.most numerous WBCbasophilic (blue) & acidophilic (red)defensins - antibiotic-like proteins (granules)polymorphonuclear - many-lobed nucleicauses lysis of infecting bacteria/fungiHIGH poly count -- likely infection
2.eosinophils - lead attack against parasitic wormsa.only 1-4% of all leukocytesb.two-lobed, purplish nucleusc.acidophilic (red) granules with digest enzymesd.phagocytose antigens & antigen/antibody complexe.inactivate chemicals released during allergies3.basophils - releases Histamine which causes inflammation,vasodilation, attraction of WBCsa.RAREST of all leukocytes (0.5%)b.deep purple U or S shaped nucleusc.basophilic (blue) granules with HISTAMINEd.related to "mast cells" of connective tissuee.BOTH release Histamine with "IgE" signalf.antihistamine - blocks the action of Histamine in responseto infection or allergic antigenC. Agranulocytes - WBCs without granules in cytoplasm1. lymphocytes - two types of lymphocytesa.T lymphocytes - (thymus) respond against virus infectedcells and tumor cellsb.B lymphocytes - (bone) differentiate into different "plasma
cells" which each produce antibodies against different antigensc.lymphocytes primarily in lymphoid tissuesd.very large basophilic (purple) nucleuse.small lymphocytes in blood (5-8 microns)f.larger lymphocytes in lymph organs (10-17 mic)2.monocytes - differentiate to become macrophages; serious appetitesfor infectious microbesa.largest of all leukocytes (18 microns)b.dark purple, kidney shaped nucleusD. Leukopoiesis and Colony Stimulating Factors (CSFs)1.leukopoiesis - the production, differentiation, and developmentof white blood cells2.colony stimulating factors (CSF) - hematopoietic hormones thatpromote leukopoiesisa.produced by Macrophages and T lymphocytesi.macrophage-monocyte CSF (M-CSF)ii. granulocyte CSF (G-CSF)iii. granulocyte-macrophage CSF (GM-CSF)iv. multi CSF (multiple lymphocyte action)v.interleukin 3 (IL-3) (general lymphocytes)3.leukopoiesis - all cells derived from hemocytoblast
E.Disorders of Leukocytes1.2.leukopenia - abnormally low WBC counta. HIV infection, glucocorticoids, chemotherapyleukemia - cancerous condition of "line" of WBCsa.myelocytic leukemia (myelocytes)b.lymphocytic leukemia (lymphocytes)c.acute leukemia - cancer spreads rapidlyd.chronic leukemia - cancer progresses slowlye.anemia, fever, weight loss, bone painf.death from internal hemorrhage or infectiong.chemotherapy & radiation therapy used to treat3.infectious mononucleosis - caused by Epstein-Barr virus,excessive monocytes and lymphocytes; fatigue, sore throat, fever; 3 weekcourseIV. Platelets (thrombocytes - "clotting")A.1.2.millimeter3.4.B.General Characteristicsvery small, 2-4 microns in diameterapproximately 250-500,000 per cubicessential for clotting of damaged vasculaturethrombopoietin - regulates platelet productionFormation of Plateletshemocytoblast- myeloid stem cell- megakaryoblast- promegakaryocyte- megakaryocyte- (large multilobed nucleus) platelets (anucleatedparts of megakaryocyte cytoplasm)
V.Plasma (the liquid part of blood)A.General Characteristics1.2.plasma makes up 55% of normal blood by volumewater is 90% of the plasma by volume3.many different SOLUTES in the plasmaa.albumin - pH buffer & osmotic pressureb.globulins - binding proteins & antibodiesc.clotting proteins - prothrombin & fibrinogend.other proteins - enzymes, hormones, otherse.nutrients - glucose, fatty acids, amino acids, cholesterol,vitaminsf.electrolytes - Na , K , Ca , Mg , Cl-, phosphate, sulfate,bicarbonate, others
VI. Hemostasis (stoppage of blood flow after damage)A.General Characteristics1.vascular spasms (vasoconstriction at injured site)2.platelet plug formation (plugging the hole)3.coagulation (blood clotting - complex mechanism)B.Vascular Spasms1.first response to vascular injury - VASOCONSTRICTION isstimulated by:a.compression of vessel by escaping bloodb.injury "chemicals" released by injured cellsc.reflexes from adjacent pain receptorsC.Formation of a PlateletPlug1.damage toendothelium of vessel2.platelets becomespiky and sticky in response3.platelets attach todamaged vessel wall to plug it4.platelets producethromboxane A2 granule release5.serotonin releaseenhances vascular spasm6.ADP - attracts andstimulates platelets at site7.prostacylin inhibits aggregation at othersites
VII. Coagulation (blood clotting)A. General Events in Clottingplatelet cells activated by damage- PF3 and/or Tissue Factor produced by platelet cells- Factor X activated- prothrombin activator (enzyme) produced- prothrombin conversion - thrombin (another enzyme)thrombin stimulates: fibrinogen---- fibrin mesh1. anticoagulant - chemical that inhibits clotting2. procoagulant - chemical that promotes clotting3. intrinsic pathway - within the damaged vessela. more procoagulants needed (I-XIII) toward PF3 and Factor Xb. allows more "scrutiny" before clotting occurs4.extrinsic pathway - in outer tissues around vessela. tissue thromboplastin (Tissue Factor) - skips intrinsic stepsstraight to PF3 and Fac Xb. allows rapid response to bleeding out of vessel (clot canform in 10 to 15 seconds)5.B.After activation of Factor X, common pathway:Factor X, PF3 (thromboplastin), Factor V, Ca -- prothrombin activator - prothrombin converted - thrombin (active enzyme)thrombin stimulates: fibrinogen - fibrin (meshwork)Ca & thrombin - Factor XIII (fibrin stabilizer)Clot Retraction (shrinking of clot)1.actomyosin - causes contraction of platelets2.blood serum - plasma WITHOUT clotting Factors3.platelet-derived growth factor (PDGF) - stimulates fibroblastmigration and endothelial growth
C.Clot Eradication (Fibrinolysis)1.healing occurs over 2 - 10 days2.tissue plasminogen activator (TPA) - causes the activation ofplasminogen3.plasminogen-- plasmin4.plasmin degrades proteins within the clotD.Factors Limiting Growth and Formation of Clots1.Limiting Normal Clot Growtha.b.blood moves too fast to allow procoagulantsfactors interfere with normal clottingi.prothrombin III - deactivates thrombinii. protein C - inhibits clotting Factorsiii. heparin - inhibits thrombin; prevents adherence ofplatelets to injured siteVII. Disorders of HemostasisA.Thromboembolytic Disorders (undesirable clotting)1.thrombus - blood clot in normal blood vessel2.embolus -blood clot/gas bubble floating in blooda.TPA, streptokinase - can dissolve a clotb.aspirin - inhibits Thromboxane formationc.heparin - inhibits thrombin & platelet depositd.dicumarol - anticoagulant, blocks Vitamin KB.Bleeding Disorders1.thrombocytopenia - reduced platelet count; generally below50,000 per cubic millimeter; can cause excessive bleeding from vascularinjury2.impaired liver function - lack of procoagulants (Clotting Factors)that are made in liver a. vitamin K - essential for liver to makeClotting Factors for coagulation
3.hemophilias - hereditary bleeding disorders that occur almostexclusively in malesa.hemophilia A - defective Factor VIII (83%)b.hemophilia B - defective Factor IX (10%)c.Genentech. Inc. - now produces genetically engineeredTPA and Factor VIII; patients do not need transfusions as oftenhttp://www.mhhe.com/biosci/esp/2002 general/Esp/folder structure/tr/m1/s7/trm1s7 3.htmVIII. Blood Transfusions and Blood TypingA.Transfusion of Blood1.whole blood transfusion - all cells and plasma; anticoagulants(citrate and oxalate salts) used2.packed red blood cells - most of the plasma has been removedprior to transfusionB.Human Blood Groups1.agglutinogens - glycoproteins on the surface of blood cells;causes "agglutination" (clumping)2.ABO Blood Groups - determined by presence or absence ofType A and Type B agglutinogen proteins on cell membraneTYPEBlood from:type Atype Btype ABtype O3.GENESPEOPLEAntibodiesA/A, A/O, O/AB/B, B/O, O/BA/B or B/Ano A or i-A,Anti-BReceiveA, OB,OA, B, AB, OO onlyagglutinins - antibodies against either A or B agglutinogen(whichever is not present) a. transfusion reaction - patient'santibodies attack the donor bloodi.A (anti-B) receives A,O (not B)ii. B (anti-A) receives B,O (not A)
iii.iv.AB (none) receives A, B, AB, O universal recipientO (anti-A,anti-B) receives O universal donorc.agglutination - when incorrect blood transfused, antibodieswill "clump" new bloodd.hemolysis - after clumping, RBCs may rupture, releasinghemoglobin, harming kidneyi.dilute hemoglobin, administer diuretics
4.Rh factor - adifferent group ofagglutinogensa.Rh positive (Rh ) - an Rhfactor is presentb. Rh negative (Rh-) - NO Rhfactorc.transfusion reaction delayed and less severe than inABO confrontationd. erythroblastosis fetalis Rh- mother antibodies attack Rh of older newborn; results inanemia and low oxygen levels (hypoxia)i.RhoGAM - serum with anti-Rh agglutinins which will clump the Rhfactor, blocking the reaction of mothers antibodiesii. exchange transfusion - directly from the mother (Rh-) to the newborn(Rh )5.Blood Typing - mixing Donors Blood with Recipient Antibodies(Anti-A, Anti-B, anti-Rh) in order to identify agglutination6.Expanding Blood Volume to Avoid Shocka.pure plasma without antibodiesb.plasma expanders - purified human serum albumin,plasminate, dextranc.isotonic saline - normal electrolyte solution isotonic toblood plasma (Ringer's Solution)7.Diagnostic Blood Testsa.bc.anemia - low hematocrit (below 35%)lipidemia - high in fat; yellowish plasmadiabetes - blood glucose level
d.infection - generally higher WBC counte.leukemia - significantly higher WBC countf.differential WBC count - counts % of each of the differentleukocytes (helps diagnose)g.prothrombin time - time for clotting to occurh.platelet count - diagnose thrombocytopeniai.complete blood count - overall blood review
Lecture: Physiology of Blood I. Components, Characteristics, Functions of Blood A. Major Components of Blood 1. formed elements - the actual cellular components of blood (special connective tissue) a. erythrocytes - red blood cells b. leukocytes - white blood cells c. platelets - cell frag
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