2. biokimia darah

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)