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  • BIOCHEMICALASPECTOFBLOOD

    AbdulSalamM.SofroDept.ofBiochemistry,Fac.ofMedicine

    YARSIUniversity

  • IntroducHon

  • AnaksayawaktudisunatdarahnyasusahberhenH,kenapayadok?

    Tiapkalisayasikatgigikeluardarah,kenapayadok? Hidungadiksayaseringmimisen.Kenapayadok? Tekanandarahsayarendah.Apasayaharusmakansatekambingterusdok?

    KadarHemoglobin(Hb)pamansayakurang.Katadokterharusditransfusi.Apakalaukurangdarahharusditransfusidok?

    Anaksayakurangdarah,apaharusdiberilaukhaH&ampelaterusdok?

    QsrelatedtoBlood

  • Iqra bismi Rabbikalladzii kholaq

    (Bacalah, dengan nama Rabb/Tuhan mu yang telah menciptakan)

    Kholaqal insaana min alaq ........ (Yang menciptakan manusia dari alaq -

    segumpal darah, sesuatu yang menempel) - QS. AlAlaq

    Venice, Italy Dec 2012

    Theverybeginningofhumandevelopment

    Fer$lizedovum

    Zygote

  • cogito ergo sum = saya berpikir maka saya ada (Rene Descartes Filsuf Prancis)

    Cesky Crumlov, Cezk Dec 2013

    Paris, France, Dec 2012

  • Teaching aims

    By the end of the lecture, students would be able to understand & describe various biochemical aspects of blood

    Reference: Murray K et al. 2000. Harpers Biochemistry, 25th ed & other lecture sources

  • Coretopics

    Introduction Composition and main functions of blood Plasma and its proteins Hemostasis and thrombosis Hemoglobin synthesis and degradation

  • IntroducHon

    Blood is a liquid tissue circulates in what is virtually a closed system of blood vessels

    Blood consists of solid elements (RBC, WBC & platelets) suspended in a liquid medium called plasma critical for the maintenance of health

  • ComposiHonandmainfuncHonsofblood

  • FuncHons

    Respiration Nutrition Excretion Maintenance of normal acid-base balance Regulation of water balance Regulation of body temperature

  • Defense against infection by WBC & circulating antibodies

    Transport of hormones & regulation of metabolism

    Transport of metabolites Coagulation

  • Composition

    Solid elements : RBC, WBC, Platelets Liquid medium : plasma consisting of water,

    electrolytes, metabolites, nutrients, proteins, hormones, etc. Water & electrolyte composition of

    plasma is practically the same as that of all extracellular fluids Once the blood has clotted (coagulated),

    the remaining liquid phase (called serum) lacks of the clotting factors (including fibrinogen)

  • Composition of Blood

    19-13

  • Red blood cells (erythrocytes)

    DeliveringOxygentotheHssues&helpinginthedisposalofcarbondioxide&protonsformedbyHssuemetabolism

    MuchsimplerstructurethanmosthumancellsmembranesurroundingasoluHonofHb(about95%ofintracellularproteinoftheRBC)

    Containcytoskeletalcomponentsimportantindeterminingtheirshape(Spectrin,ankyrin&otherperipheralmembraneprotein)

  • Red blood cells (cont.)

    Possessmanybloodgroupsystems(eg.ABO,Rh&MNsystems)TheABOsystemiscrucialinbloodtransfusion

    TheABOsubstancesareglycosphingolipids&glycoproteinssharingcommonoligosaccharidechains

  • Redbloodcells(cont.)

    Lifespan:120days TheirproducHonisregulatedbyerythropoieHn(synthesizedinkidney&isreleasedtothebloodstreamandtravelstobonemarrowinresponsetohypoxia)

  • Redbloodcells(cont.)

    About2millionRBCenterthecirculaHonpersecond

    MetabolicallyacHve(butunique&relaHvelysimple)(facilitateddiusioninvolvingspecicprotein,i.e.glucosetransporter/permease,butnotinsulindependentlikeinmuscle&adiposecells)

  • Redbloodcells(cont.)

    SOD,Catalase&GlutathioneprotectcellsfromoxidaHvestress&damagelinkedtoHexoseMonophosphateShunt(HMS=PentosePhosphatePathway)

  • Leukocyte(WBC)

    Thereare3groups:granulocytes(polymorphonuclearleukocytes=PMNs):NeutrophilsBasophilseosinophils

    monocyteslymphocytes

  • NeutrophilsphagocytosebacteriaandplayamajorroleinacuteinammaHon

    Basophilsresemblemastcells,containhistamin&heparinandplayaroleinsometypesofimmunologichypersensiHvityreacHons

    EosinophilsareinvolvedincertainallergicreacHons&parasiHcinfecHons

  • Monocytesareprecursorsofmacrophageswhich,likeneutrophilsareinvolvedinphagocytosis

    LymphocytesBlymphocytessynthesizeanHbodies,Tlymphocytesplaymajorrolesinvariouscellularimmunemechanisms,suchaskillingvirallyinfectedcells&somecancercells

  • Platelets(Thrombocytes)

    cell-likeparHclessmallerthanRBCsandWBCs.

    Helpwithcloingprocessbygatheringatbleedingsiteandclumpingtogethertoformaplugthathelpssealthebloodvessel.

  • Bloodgroupsystem

    Very important in blood transfusion Determined by antigens in blood cell

    membrane and antibody in plasma ABO blood group system:

    Blood group A : antigen A, antibody Anti B Blood group B : antigen B, antibody Anti A Blood group AB : antigen A & B, antibody non Blood group O: antigen non, antibody anti A &

    anti B

  • Genes&theirproductinABObloodgroupsystem

    GeneH:fucosyltransferaseGeneA:N-acetylgalactosamineglycosyltransferaseGeneB:galactosyltransferaseGeneO:inacHveenzyme

  • Gene product Antigen Gene product Antigen

    H & A

    H & B

    H

    H P s r u e b c s u t r a s n o c r e

    Tr-A

    Tr-B

    O

    Precursor substance

    Tr-H

    hh

  • RBCPrecursorStructure

    Glucose

    Galactose

    N-acetylglucosamine

    Galactose

    Precursor Substance (stays the

    same)

    RBC

    Source: cls.umc.edu/COURSES/.../ABOsystem.ppt

  • FormaHonoftheHanHgen

    Glucose

    Galactose

    N-acetylglucosamine

    Galactose

    H antigen

    RBC

    Fucose cls.umc.edu/COURSES/.../ABOsystem.ppt

  • FormaHonoftheAanHgen

    Glucose

    Galactose

    N-acetylglucosamine

    Galactose

    RBC

    Fucose N-acetylgalactosamine

    cls.umc.edu/COURSES/.../ABOsystem.ppt

  • FormaHonoftheBanHgen

    Glucose

    Galactose

    N-acetylglucosamine

    Galactose

    RBC

    Fucose Galactose

    cls.umc.edu/COURSES/.../ABOsystem.ppt

  • Group O Group A

    Many H antigen sites

    Fewer H antigen

    sites

    A

    A A

    A A

    Most of the H antigen sites in a Group A individual have been

    converted to the A antigen

    cls.umc.edu/COURSES/.../ABOsystem.ppt

  • GeneHcs

    The H antigen is found on the RBC with the Hh or HH genotype, but NOT from the hh genotype

    The A antigen is found on the RBC with the Hh, HH, and A/A, A/O, or A/B genotypes

    The B antigen is found on the RBC with the Hh, HH, and B/B, B/O, or A/B genotypes

  • HanHgen

    Certain blood types possess more H antigen than others:

    O>A2>B>A2B>A1>A1B Greatest

    amount of H Least

    amount of H

    cls.umc.edu/COURSES/.../ABOsystem.ppt

  • Plasmaanditsproteins

  • Plasmaproteins

    Total plasma protein approx. 7.0-7.5 g/dl A complex mixture of simple & conjugated

    proteins such as glycoproteins & various types of lipoproteins, thousands of antibodies

    Can be separated by: sodium or amm. sulfate into three major

    groups fibrinogen, albumin & globulins electrophoresis using cellulose acetate into

    five bands albumin, 1, 2, & globulin

  • Cont. Concentration of plasma protein is important in

    determining the distribution of fluid between blood & tissues

    Osmotic pressure (oncotic pressure) exerted by plasma protein is approx. 25 mm Hg. Hydrostatic pressure in arterioles is approx.

    37 mm Hg a net outward force of about 11 mm Hg drives fluid out into interstitial spaces.

    Hydrostatic pressure in venules is approx. 17 mm Hg a net force of about 9 mm Hg attracts water back into circulation

  • Cont.

    The above pressures are often referred to as the Starling forces.

    If plasma protein concentration is markedly diminished (eg. due to severe protein malnutrition fluid is not attracted back into the intravascular compartment and accumulates in extravascular tissue spaces oedema

  • Cont.

    Most plasma proteins are synthesized in the liver

    Plasma proteins are generally synthesized on membrane-bound polyribosomes

    Almost all plasma proteins are glycoproteins

    Many plasma proteins exhibit polymorphism

  • SomefuncHonsofplasmaproteins

    Antiprotease (antichymotrypsin, 1 antitrypsin, 2 macroglobulin, antithrombin)

    Blood clotting (various coagulation factors, fibrinogen)

    Hormones

  • Immune defence (Ig, complement proteins, 2-microgloblin)

    Involvement in inflammatory responses (acute phase response protein eg. C-reactive protein, 1-acid glycoprotein

    Oncofetal (a1-fetoprotein = AFP) Transport or binding proteins such as:

  • Cont. albumin for bilirubin, FFA, ions, metals,

    metheme, steroids, other hormones, variety of drugs

    Ceruloplasmin contains Cu but albumin is more important in physiological transport of Cu

    Corticosteroid-binding globulin (transcortin) Haptoglobin binds extracorpuscular Hb Liproproteins (chylomicron, VLDL, LDL,

    HDL)

  • Cont. Hemopexin Retinol-binding protein Sex hormone-binding globulin Thyroid-binding Transferrin Transthyretin (formerly pre albumin, binds

    T4 & forms a complex with Retinol-binding protein)