topic 3 blood

8/7/2019 Topic 3 Blood

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The Blood


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The blood contains a solid part and a liquid part.The solid part consists of the blood cells and the liquid part is the

plasma.

If one takes a sample of blood, treats it withan agent to preventclotting, and spins it in a centrifuge,

the red cells settle to the bottomthe white cells settle on top of them forming the "buffy coat".

The fraction occupied by the red cells is called the hematocrit.

Normally it is approximately 45%. Values much lower than this are asign of anemia.

Thus hematocrit is the percentage of red blood cells in the blood.


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General Components of Blood

Whole Blood can be broken into 2 main components:

Plasma (46-63%)

Formed elements (37-54%). Plasma itself consists primarily of:

Water (92%) Plasma Proteins (7%) Othersolutes (1%).

The formed elements consistof: Red blood cells (99.9%) White blood cells (>0.1%) Platelets (>0.1%).


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Functions of the Blood

Blood performstwo major functions: transportthrough the body of

oxygenand carbon dioxide

food molecules (glucose, lipids, amino acids)

ions (e.g., Na+, Ca2+, HCO3)

wastes (e.g., urea)

hormones

heat

defense ofthe body againstinfectionsand otherforeignmaterials. All the WBCsparticipate inthese defenses.


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Other functions of blood. They include:

Transportof dissolved gases, nutrients, hormones, andmetabolic wastes.

Regulation ofthe pH and electrolyte composition ofinterstitial fluidsthroughoutthe body.

Restriction of fluid losses (in eventofinjury).

Defense againsttoxinsand pathogens.


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Composition of Plasma

Plasma isthe straw-colored liquid in which the blood cellsaresuspended. Itisthe liquid portion ofthe blood

Component Percent

Water ~92

Proteins 68

Salts 0.8

Lipids 0.6

Glucose (blood sugar) 0.1


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Serum Proteins ( in the Plasma )

Proteinsmake up 68% ofthe blood. They are aboutequally divided betweenserum albumin and agreatvariety ofserum globulins.

After blood is withdrawn froma veinand allowed to

clot, the clotslowly shrinks. Asitdoesso, aclearfluid called serumissqueezed out. Thus:

Serum is blood plasma without fibrinogenand otherclotting factors.


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Formation of differenttypes of blood cells fromstemcells.


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A Red Blood Cell

Red blood cell synthesisis knownas erythropoiesis. Inthe adult, allblood cell formation (i.e., synthesis of RBCs, WBCs, and platelets)occursinthe red bone marrow.


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RED BLOOD CELL FORMATION ( Erythropoiesis )

In health, erythropoiesisisregulated so thatthe number ofcirculating erythrocytesismaintained withinanarrow range.Normally, a little lessthan l% ofthe body'stotal red blood cellsareproduced per day and these replace an equivalentnumberthathavereached the end oftheir life span. Howeverthatstill representsahuge 200,000,000,000 cells

Erythropoiesisisstimulated by hypoxia (lack of oxygen). However,

oxygen lack doesnotactdirectly onthe haemopoietictissues butinstead stimulatesthe production ofa hormone, erythropoietin.This hormone thenstimulates haemopoietictissuesto produce redcells.

Erythropoietinisa glycoprotein. Itisinactivated by the liverandexcreted inthe urine. Itisnow established thaterythropoietinisformed withinthe kidney by the action ofarenal erythropoietic

factorerythrogenin. Erythrogeninispresentinthe juxtaglomerularcells ofthe kidneys

and isreleased into the blood inresponse to hypoxiainthe renalarterial blood supply.

Various other factorscanaffectthe rate of erythropoiesis byinfluencing erythropoietinproduction.


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Whathappensto the iron?Iron will be stored inthe liveras well astransported to red bone marrow (to beincorporated innew RBCs) and othertissuesIronistransported inthe blood asaproteincomplex called transferrinand stored withinlivercells.


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Hematocrit

An essential testused to examine blood isthe hematocrit. The hematocritis

ameasure ofthe percentage of whole blood occupied by RBCs. Average value inamale is 47% (range of 42-52%).

Average ina female is 42% (range of 37-47%).

HCT can be determined by centrifuging asample of blood so thatall theformed elementscome outofsuspension - we will do thisin lab!

Since leukocytesand plateletsmake up far lessthan 1% ofthe blood, itcan

be assumed that: (100-HCT) = % of blood occupied by plasma.


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Types ofWBCs:

They can be classified asto whether ornotthey containgranulesthattake upWright'sstainand are visible withthe lightmicroscope.

Granulocytes Contain visible stained granules. Includes:

Basophils Eosinophils Neutrophils. Agranulocytes

Do notcontainstained visible granules. Includes: Lymphocytes Monocytes.


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- 50-70% ofcirculating WBCs.- Cytoplasmispacked with pale "neutral" colored granulesthatcontain bactericidalcompounds.- Mature neutrophils have asegmented nucleus - and are thus knownaspolymorphonuclear leukocytes.

- About12 umin diameter.- Highly mobile and generally the firstWBCsto arrive atasite ofinjury.- Specialize inattacking and digesting bacteriathathave been "marked" fordestruction.- Lifespan ofabout6 hrsto a few days.

Neutrophils


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2- 4% ofcirculating WBCs. Similarinsize to neutrophils buthave reddish-orange staining

granules. Functions:

Phagocytize antibody-coated bacteria, protozoa, and cellular debris. Exocytose toxiccompounds onto the surface ofpathogens, particularly

large multicellularparasitessuch as flukes orparasitic worms.

They increase in # dramatically during aparasiticinfection. Also sensitive to allergensand increase in # during allergicreactions

as well. Typical lifespan of 8 - 12 days.

Eosinophils


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Basophils

Lessthan 1% ofcirculating leukocytes. Smallerthan eosinophilsand neutrophils. Contain granulesthatappear deeppurple or blue.

Migrate to injury sitesand discharge the contents oftheir granules: Histamine

Vasodilatorand increaser ofcapillary permeability.

Heparin Ananticoagulant.

These 2 chemicals enhance the local inflammationinitiated by mastcellsandattractotherWBCs.

Lifespanisnotcertain.


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Monocytes

2- 8 % ofcirculating WBCs. Almost2 x as big asan RBC. Nucleusis large & tendsto be oval or kidney-shaped. Individual monocytesuse the bloodstreamasa highway,

staying inthe circulation for only about24hrs before anentering peripheral tissuesto become atissuemacrophage, anaggressive phagocyte.

Lifespancan be upto several months.


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Lymphocytes

20 30 % ofcirculating WBCs. Slightly largerthan RBCs. In blood smears, youtypically only see athin halo ofcytoplasmaround arelatively large

nucleus. Continuously migrate fromthe bloodstreaminto the peripheral tissuesand back into the

bloodstream. Circulating lymphocytesare only aminute fraction ofthe total # inthe body. Mostare in

otherconnective tissuesand in lymphatic organs. Circulating blood contains 2 mainclasses of lymphocytes:

T Lymphocytes: Defend against foreigncellsand tissuesand coordinate the immune response. B Lymphocytes: Produce and distribute antibodies - proteinsthatattack foreignmolecules.

Lifespan 2 to 3 days orabout200 days.


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Normal values of RBC and WBC


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Hemoglobin (Hgb)

Men:1418 gramsper deciliter (g/dL) or 8.711.2 mmol/L (SI units)Women:1216 g/dL or 7.49.9 mmol/L

Red blood cell (RBC) count

Men: 4.66.2 million RBCspermicroliter (L) or 4.66.2 x 1012/Liter (SI

units)

Women:

4.25.4 million RBCsper L or 4.25.4 x 1012/L

Children:

4.64.8 million RBCsper L or 4.64.8 x 1012/L

Hematocrit (HCT)

Men: 40%54%

Women: 37%47%


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Red blood cell indices

Mean corpuscular volume (MCV):

80100 femtoliters (fL)

Mean corpuscular hemoglobin (MCH):

2832 picograms (pg)

Mean corpuscular hemoglobin concentration(MCHC):

3236 gramsper deciliter (g/dL)


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WBC count: 4,50011,000/L polymorphonuclearneutrophils: 1800

7800/L; (5070%)

band neutrophils: 0700/L; (010%) lymphocytes: 10004800/L; (1545%)

monocytes: 0800/L; (010%)

eosinophils: 0450/L; (06%) basophils: 0200/L; (02%)


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Platelet (thrombocyte) count

140,000450,000 plateletspermm

3or 150400 x 10

9/Liter (SI

units)


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Platelets

Plateletsare cell fragmentsproduced frommegakaryocytes. Blood normally contains 150,000350,000 permicroliter (l) orcubicmillimeter (mm3).

Thisnumberisnormally maintained by a homeostatic(negative-feedback) mechanism .

Ifthis value should dropmuch below 50,000/l, there isa danger ofuncontrolled bleeding because oftheessential role thatplatelets have in blood clotting.

Plateletscontainschemical substances or blood factorswhich play amajorrole in blood clotting.


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The production ofplateletsiscalled thrombopoiesis Flattened, disk-like cell fragmentsthat are about1um by 4um. Actas aparticipantinthe vascularclotting system. Sometimesreferred to asthrombocytes. Continuously being replaced. Each plateletcirculates for 9-12 days

before being removed by splenicmacrophages. On average there are 350,000 plateletsperuL of blood. Produced inthe bone marrow. Large cellscalled megakaryocytes

release fragments (platelets) into the circulation


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Formation of Platelets


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This looping diagrammaticanimationshowsthe process ofplateletformation fromamegakaryocyte


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Whatdo platelets do?

Transportofchemicalsintegral to the

clotting process. By releasing enzymesand other factors,

platelets helpinitiate the clotting process.

Formation ofatemporary patch (called aplateletplug) inthe wall ofa damagedblood vessel.


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Blood clotting

Vascular Phase Damage to the wall ofa blood vessel will obviously affectthose cellsthat

comprise the wall. The endothelial cells (simple squamous epitheliumthat linesthe blood vessel

lumen) atthe site ofaninjury will: Have their basementmembrane exposed. Release a variety ofchemicals. Become "sticky."

The smooth muscle cellsinthe blood vessel wall also respond to damage. TheyCONTRACT. By contracting, the blood vessel diameter decreases which helpstoreduce blood lossand reduce the pressure onthe damaged area.


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PlateletPhase Platelets beginto attach to the sticky endothelial cells, the basementmembrane, and to

exposed collagen fibers. Asplatelets "stick," they are activated and they release chemicalsthat: Attractand activate more platelets. Cause local vasoconstriction (contraction of blood vessel smooth muscle and asubsequent

decrease inthe diameter ofthe blood vessel lumen).

Eventually, we are leftwith amass ofplateletsthattemporarily plugsthe leak inthedamaged blood vessel wall.

Itshould be noted thatintactendothelial cellsrelease achemical called prostacyclin

which inhibitsplateletaggregation. Thisrestrictsthe plug to the site ofthe damage.


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Coagulation Phase Now we need to create amore permanentseal thatcan effectively coverthe break while

repairstake place. In other words, we need aclot. The coagulationphase isasequence ofchemical reactionsthatculminate inthe

conversion of fibrinogen (asoluble circulating plasmaproteinmade by the liver) into ameshwork ofthe insoluble protein fibrin.

The fibrinmeshwork will grow and coverthe surface ofthe plateletplug. RBCsandadditional plateletsare trapped inthistangle forming a blood clotthatwill effectively sealthe walls ofthe damaged blood vessel.

Coagulationrequirescalciumas well asclotting factors - several differentproteinsprimarily synthesized by the liver.

Many clotting factorsare proenzymes (inactive enzymes) thathave to be converted to activeenzymes before they can directessential reactionsinthe clotting process. The synthesis ofsome ofthe clotting factorsrequires vitamin K.

During the coagulationphase enzymesand proenzymesinteract. The activation of oneproenzyme createsanactive enzyme thatactivatesanotherproenzyme thatwill thenactivate athird and so on yielding achainreaction orcascade. Youcanthink ofit kind oflike arow of dominos falling down.


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There are actually 2 maincascadesinvolved inthe clotting

process: the extrinsic pathway,and intrinsic pathway.

Extrinsic Pathway Begins with the release oftissue factor by damaged endothelial cells or

peripheral tissues. The greaterthe damage, the more tissue factorreleased, and the faster

clottingwill occur. Ina few shortsteps, achemical called prothrombinactivator will have

been formed. Because only a few stepsare required, the extrinsic pathforms prothrombinactivatorratherquickly.

Intrinsic Pathway Begins with the exposure ofcollagen which startsthe activationcascade

ofseveral proenzymes eventually resultinginthe production ofprothrombinactivator. Because there are several steps, the intrinsic path doesnotmake

prothrombinactivatoras fastasthe extrinsic path. However, multiplestepsallows formore amplification which meansmore prothrombinactivator will be made.


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Blood clot( electronmicroscopy )


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Howdowe get rid ofthe clot?

Fibrinolysis As repairsproceeds, the clotgradually dissolves. This

dissolution is knownasfibrinolysis.

Fibrinolysis beginswith the activationofthe proenzymeplasminogen by 2 enzymes: Thrombinactivated in the commonpathway.

Tissue plasminogenactivator releasedby damagedtissue.

Once plasminogen is turned intoplasmin, the plasmindigests the fibrinstrandsanderodes the foundationof

the cl

ot.______________________________________________

Plasmin

BLOOD CLOT ---------------------------- clotdissolved


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topic 3 blood

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