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la" nll:q/l (10'/ mmo1/1)

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fracas

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- ::li'Jtuo 15·6 pH Con~idcralion~ in ChcmLstry and Physiology(:1) Rcl~Hionshlp of pH to the n:blivc COIKcnlr:llions or!-t • .-;lnci base (OH-) under chcmico.Hy ,.neutral, nciJic. and ;dkalilh: (Ondiliolls. (b) Pbsm;l pH j'.mgc under norm:li. acidosis, and31kalosis c.:llndltions.

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• . 1ho prlncip'al rolo 9f"h~'blood,• -"'. 01' ,'~I. .! ~" • .• • • •

The blood i.s do vical vehicle of communicacion bc[wecn chetissues of multi·cellular oQpnisms. Its numerous functions··include (he following:

(1) Jclivcry of nutrjc.:nc~ from J.(lit to ci1i.5uc&;(~) ,",UII (.'xciluoJje: 'he (,:11 rri 11).('-' of' UXYJ.(CJl {rum clH.o' JuoJ.(" (0

che.: ci,.IOucs. uno (urbun dioxiJc frum the Ci,IOU(""J, Co ch,-'lungs.j

(3) .transport of the waste produces of metabolism from thesites of production to the sites of disposal;

(4) carriage of hormones from endocrine ,glands to specifictarget tissues; ano

(~) protection 1lt;llinst invudinH, ort;anisms-its immuno·logical role.

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VARIATIONS UNDER DIFFERENT PHYSIOLOCALCONDITIONS

1. SEX: for males the blood volume is 10% higher than infemales. This is due to greater number ofRBc.

2. PREGNANCY: B.V. rises due to increase in both cells &plasma. In pregnant women B.V. increases on the average byabout 20 to 30%, in the last few weeks of pregnancy.

3.MUSCULAR EXPERCISE: It raises B.V. probably due 10contraction of spleen.

4. POSTURE: In erect posture there is about 15% diminutionof total plasma. It passes out into the tissue spaces.

5. BLOOD PRESSURE: Rise ofB.P. lowers B.V. bypressing out more fluid into the tissue spaces.

6. AL TITUDE: At higher altitude the BY will rise. Due tohypoxia the number ofRBc will increase.

7. ADERNALINE INJECTION: Raises BY probably bycontraction of spleen.

;~.wThQplasma pr"t~ins geller.al'y aTe synthesizeq by 'the livu,

",,'lIh the e)lcepiion ofth~ 9amma ~IQbulil1s~which are pro-ollted \)J \Y!Y'lphO(Jk~.

Summary ofthe functions of plasma proteins1 Transpo.rt functions ((X- and ~-globulins).2 Defensive (immunoglobulms).3 Reserve of body proteins4 Osmotic functlOn (albumm) through control of tkexchange )f fluid between blood and tissues5 VISCOSity of plasma is due mainly to fibnnogen andglobulins6 Fibrinogen is 'he precursor of fibrin In the blood clot.Prothrombin IS an (X2-globulin and most of the remainingclotting factors are ~-globullns.

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the'plasma..The:percent volumept:;rc(jmeasLI.red. In this. example, tile'hpm,ot",-,it'id

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FiH. [tit Silcs of activc hnCJllatopoictic Illarrow (rcd ll1arCCHv,)' in~hildrell allli "uul!s. There is a similar "mount of red marrow (.1000 to1·500g), ill each uespi!e the uiffercnces in body weight.· (FromIlierman, H. R. (l'.!G I) III F'IIICliolls oj the Wood, cd. MacFarlane, It.:.;. & Robb-Smi!h, A. H. T, p. 357: Oxforu: Ulackwcll.)

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Regulation of erythrpoiesis

1- 02 supply (hypoxia or hyperoxia)

2- Vitamines (B12, folate, .... etc.)

3-lron

4- Proteins

5- Trace etements (copper, cobalt)

6- Health bone marrow

7- Live,' (storage, protein synthesis, hormone

synthesis)

8- Hormones: (erythropoieten, androgens,

thyroid hormones, gl'Owthhormone and

corticosteroid hormones)

Hematopoietic Stem Cells. i

Kid~ f'-"~~-·-:·ro::t~oblasts

Erythropoietin .1.~'t Red Blood Cells

Decreases {tI ,

~ _. - ~ ~ I Tissue Oxygenation

,',?~\

Decr~ases

Factors that decreaseoxygenation

1. Low blood volume2. Anemia3. Low hemoglobin4. Poor blood flow5. Pulmonary disease

Figure 32-4

Function of the erythropoietin mechanism to increase productionof red blood cells when tissue oxygenation decreases

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FIGURE 22·13 :. . .' ,Steps j'n the a~sOrplio)~ oJ iron'rrulL the i'nlcstinc ')' ./cllld its transport into ll~c blood. ... ~

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1. Iron deficiency is estimated to affect about

30% of the world population.

2. Iron deficiency Anemia is still the most

important deficiency related to malnutrition.

3. Iron deficiency anemia (IDA) and thalassemia

trait (TT) are the most common forms of

microcytic anemia.

4. Some discrimination indices calculated from

red blood cell indices are defined and used for

rapid discrimination between TT and IDA.

5. Iron-deficiency anemia (IDA) is a common

clinical problem throughout the world and an

enom10US public health risk in developing and

even in industrialized countries.

6. Traditionally, several methods other than

semm ferritin were used to assess IDA.

1 nm

Figure 27-10. Diagrammatic representation of a mole-'cule of hemoglobin A, showing the 4 subunits. There aretwo (~ and twO-f)-polypeptide chains, each coiiliiinTngaheme moiety. These moieties are represented by thedisks. (Reproduced, with permission, from Harper HA etal: Physi%gische Chemie. Springer-Verlag, 1975Y

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Figure 27-12. Dla"rammatic reprosentation 01 a molo-culo 01 hemoglobin A, showing the 4 subunits. Thera me2 " and 2 I> polypeptide chains. each containing a hememoiely. Tho sa moiollos aro roprGsented by tho disks.(Reproduced. with permission. Ir.om Harper HA et at:Physiologischc Chernie. Springer-Verlag, 1975.)

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Birth 3Age (months)

i Figure 27-14. Development of human hemoglobin\. chains.

6

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90§, hemoglobin at>- 80 40 mm Hgx0

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c:0 60ac,0

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o 10 20 30 40 50 60 70 80 90 100Partial pressure of oxygen in mm Hg

Figure 17.15 Hemoglobin Dissociation Curve for Oxygen in an AdultHuman. The curve shows the extent to which hemoglobin pickfi,. up orreleases oxygen as the oxygen pressure in the blood changes\J.JVVhenblood passes through the lungs, where the partial pressure of oxygenis about 100 mm H,g"the i:lemoglobin becomes about 97_percent sat-urated with oxyge~ut when blood passes through distant-tissues,where the partial pressure of oxygen is ordinarily about 40 mm Hg, thehemoglobin releases about ~!i12.£,-"eDt..of its oxygen. (Adapted from J.W. Severingl18us, J. Appl. Physiol. 21 ("1966] :1111;)

'0g 20:c~E. 15

Hb 14 g/dl

Hb 10 g/dl

c'"coua

Hb 7 g/dl

mmHg

Po,

Fig. 6.12 Effect of anaemia on oxygen content of the blood atdifferentPo2 values.

~t is evident that the quantity of oxygen carried in avolume of blood is dependent on the P02 as well as thehaemoglobin concentration"X:The percentage saturation ofhaemoglobin with oxygen is dependent on P02 and totallyindependent of haemoglobin concentration. If oxygencontent (instead of percentage saturation of haemoglobinwith oxygen) is plotted against Po" the level of the curvewill be dependent on the haemoglobin concentration of thesample of blood (Fig. 6. I25"But when plotting percentagesaturation against P021 as is usually done, the curve willalways be the same, whatever the haemoglobin concentra-tion is, if other factors remain the same.--j

ab, 1:0Q

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f>Q 83.5 O.l~)GO 89 O.Wlu 92.7 O.LIno 94.5 n.';!'"90 96.5 0.27100 97.5 O.:lU

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10 20 30 ~O GO 60 70 80 90 100 110

PO, (mm Hg)

Figure 35-2. Oxygen-hemoglobin dissociation curve. pi-I"7.~O. temperature 3()OC. (Redrawn and reproduced, willlpermission, from Com roe JI-l Jr et al: The Lung: ClinicalPhysiJ/ogy and Pulmonary Function Tests, 2nd ed. YearBool<, 1962.)

Hb, -I- 0, ", Hb,O,Hb,O,I· 0, ", Hb,O,Hb,O, -I- 0, '" Hb,O,Hb,O, -I- 0, '" Hb,OB

iCol1lbination oC the firsthellle ill Ihe I·Ib InolcClilc with O2 increases the af-fillity or the secolld heme for O2, and oxygenationof the second iller-eases tire affinity of the third,etc, so that the affinity of !-Ill for the fourth O2moleclile is In;\I\Y fillles Ihal ror the fit·sl.. - ...

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peo2 40mmHg (S.33kPa)Temp = 37°C

IPSO = 26mmHg (3.46kPa)

fL __ ,-'I!...J_..J5,-- __ -.---_----"OT __ ---,-__ ';C5:....,kPa40 80 'DO 120mmHg20 60Oxygen partial pressure

Fig. 13.6 The oxyhemoglobin dissociation curve for a PeD2 of5.33 kPa (40 mmHg) at 37 cc. Under these conditions, the p~ovalue is 3.46 kPa (26 mmHg), ;1., rhe Po] in arrerinl blood (97 percem saruraccd); V, the Po:! for mixed venous blood (5.33 kP" or40 mmHg) at which value the hemoglobin i::; still 75 per cems:}rurared. Note thac as dle Po:! falls below S kPa (60 mmHg) the

'. curve becomes progrtssively stec::per.

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Partial pressure of oxygen in mm HgFigure 17.17 Effect of 2,3-Diphosphoglycerate

• > • • • • , (DP.G) 'on Oxygen Dissociation from Hemoglobin .."i-\()'The. formation of extra DPG in 'red blood cells, as

. "occurs at high altitudes, shifts' the dissociationcurve to the right. In other words, DPG promotes

;;·the release of oxygen from hemoglobin. (Modifiedand reproduced with permission from J. H. Com-roe, Jr., Physiology of Respiration, 2d ed., p. 185 .. Copyright © 1974 by Year Book Medical Publishers,Inc., Chicago.)

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o. 20 , 40 60 80 100Partial pressure of oxygen in mm Hg

Figure 17.18 Effects of Mammalian Size on Oxy-gen, Dissociation from Hemoglubin. Small mam,".mals release oxygen more readilyfrom hemoglobin:.thando large mammals, This difference is probably:-related to the greater need far oxygen in small~_.manimalsto support a greatet' heat production per,unit of body weight. (Rept'inted from K,Schmidt-Nielsen; Federation Proceedings 29 [1970] :1529:)

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diagnostic evaluation 01' crythrocytc function it is lIsuallynecessary to meas\lre three quantities: the red cell col/nl.RCC (~L1-I), the ilelllog/oi>in CIlII CCII I ral iOIl o/Iile blood [I'Ibj(gil), and the ilelllatocril I-IC1~ From these, three othercharacteristic raramctcrs can be derived: the mean corp IIS- .

clllar ilelllogloi>in MC!!, the lIIel/lI COrpllsCillar ilel1log/ohinconcelltralion MCH C, anu the lIJeall corl'lIsclllar' voillmeMCV, Thc relationships undel'iying theseealculations arereflected directly in the definitions of the parameters andarc summarized in thc rollowing diagram:

[J Ib1

/~l!:!!i = MCH MCHC = [Hbl~C Hcr

I IRCC HCT~.~/

MeV = \lCTl<.CC

Given, ror ex,ll11rlc, that I\CC = S, I06~II, [Hb] = 1S0g/1nnd 1·ICT = (lAS, the othcr parnmctc/s al'c ns follows:MCI-! = JOpg, Melle = JJJgjl, and MCV = 0,09'!O-6fil = ')(l n (l'cl11to!itcrs) = ')0 pm] (thc conversionamong IInits is given Oil pp, 7,)(JI".j.

• Values for Ccntr,i1 !:uropc; lor North Amcrica (accord-ing to Winlro~c) MCH =' 29 PS

Mean Corpuscular Hemoglobin (MCB), "r\y :·;rl;"· .I,-,, 11·,..."';r.,.~• ..•f' vjrir1',j

of hemoglobin in the red blood cell.Weight of hemoglobin

in 1 ~I of bloodMCH = Number of rod blood colis

In 1 J-I.l of bloot!

If:1 g = 1011 pg

1 ml = 10J p.!

Then:Weight (in pg) of bernot;lobiti in 1 11.1of hlood

11001\nglo!J[n x In,'' pg

100.X 101 JA-\= Hemoglobin x la' pgJjl.l

If:

Hemoglobin = 15.0 g/dlRed bluod cell count = 5,000,000/).11

Thell:

= 30 pg

. \MCH "'" Homoglobin x 10 pg

Red blood cell count ill millionsNormal v;,\[uu for tho Mel-!: 27-31 pg

IlISCUSSION

The MCH fndicntcs the amount of hemo-globin in the red blood cell and shouldalways correlate with the Mev andIvICHC. An MCI-Ilowor thaI I 27 PC is foundin microcytic anemia and [llsa wilh nor-mocytic. hypochromic red blood cells. Anclcvalr.d MCH OCcurs in 1I1Q.crocytic anC)-mias and in som[~ cases of spllcrocytu:o;isin which hypurchromil1 rnily be prc~jt)nl.

jldoan Curpuscul~r HcnwgillhinConccntration (MCI-IC)

fill.:! ivll.l-l.l. .l,'j all expu.;;;j;jJ.UJ.i· 01 lUi.:

avewgc conccnll'8Lion of hemoglobin inthe red blood cells, It gives the ratio of Ih8wci[lhL of hCll'lOlliouin Lo Lho volume of Lhored blood cell.

MCHC = Hemoglobin in g/dlHCI1Hllocrilidl

x 100 (to convorl 10 'Xl)

If:

Helllogiobin = 15.0 g/dlHnU\alocril ,= 45%

MCHC = l~.U g/rll x~2. 'X,4~ volumes/d]

= 0;1°/1.1

Therefore, the form ula:

MCHC = HcmogJouj 11 x 'I 00 (r~HClllulocril

Norma! vulue [or Ihe IvJCllC: 3~-3G%

IJlSCUSSION

The MCl--lC indicates whelher the redblood cells are normochromic, hypo-chromic, or hyperchromic, 1\;1 Mel Iebelow 32% indiCates hypochrolllia, anMCI-IC above 3{)'),u indicates' hyper-chromia, and ret! blood cells with a norma ii\'ICHC arc termed normochromic,

,~.:' ,;:; ..

Mean Corpuscular Volume (MCV)The MCV indicates,the average volume

of the red blood cells. ' '...- ~Volumo. of fl.:ld blood colis ill

Mev = romlolil;,rr. (fllil,1 of blood'Hod blood cull'/Id of blood

If:HCl11nlocrH = 45% (or 0.'15)

J~od blood coJl'oounl = 5.000.000/1'-1, (o.r 5.0 X 10"/1'-1)

1 1'-1= 10' fI

Then:

MCV = 0.45 x 10' II/I", 5,0 X 10'/1'-145 x 10 fI

= 90 fI

Therefore, the formula:

MCV = ' Hemulucril X 10 " fIRed blood cell count in millions

Normtll vuiue for the Mev: 00-97 fl

DISCUSSION

The MeV indicates whether the redblood cells appear normocytic, microcy-tic, or macrocytic. If the Mev is less than80 fl, the red blood cells are microcytic, Ifthe Mev is greater than 97 fl, the red bloodcells arc macrocytic. 1£the MeV is withinthe normal range, Ihn red blOOd cells arenormocytic.

.1l

I'

illUui"cOJEOJI:

(; I~V>NVIu::;:

range of graduation

height of blood column

length ~f tube

internal diameter of tube

amount of blood

l

Sedimentation Rate

Wcslcrgren

o to 200 nun-------,200 m.m'

300 nll?

~

Wiolruoc

o to 100 nun (10 em)

~120 nun

2.5 mm

2 ml ,.l ml

Fig. 122. Sedimentatio;l rate tubes.

305

Cutler

Ow 40 111m

50 111m

70 111m

5.0mm

I 1111

'"••::I-;;;.-;e..oZ'" "0o..cti~

coV)

EEBB

00:00

ER.YTHROc.yTe S&DIMSHTA'T'ONlATa

When anticoagulated whole blood isallowed to stand fOYtI period oftimeJ thered blood cells setl:le. out trom {he plasma.

7(-The ,Me at which the f'f.c{ blooc\ cells {allis known as tt'le erythrocyte .s~dim ento.fion~9 (EStl). ~format\on of+h~ftd bloGod Cfltt.~.\) ~-I-~-"r \\\

)1 I /

r I_'~~!h..... ! / ("."~~Ih • •,, \J~J~..

*Xhe. E5R is aHeded mainly by th rce fac·~-..t. ER)THROC'Ylll.(si2e,shape,cell .cC.llJnf)fI factor of ~h ief ·,rnpor~af\ ceo In tfe.ier-

minil'l9 the. (ai-e offal! oHhe. re~ bloool ~etlsis 1l'le siu or ma~s (Sf the fa/l,n9 par~,cre.

t\.ihe.large.r th«. partic.le, ihe .fClsf-er its fllteoHilll.Macroqte~tel'ldt6 settle 1\"\O(C! rapidl-ythan microc.ytes.7\.Re~ blood c.~lIs+ha~ show an aHH~Hon intheir shape, sl4ch as sickle cells Clod spher-DC)lte.S, c1re un.;)ble to form rouleauy anc.(their ~"C rate is decre~se.d.~n 'iitv!.'e 8(H!mi!!

ESR i;ei~~dteci.ln polyc)ltnemicHhe €SR '$t'lMm al.

j):. PLASMA CAMpOsnrotJfhe. plasma Com po~ition i!io \he sinql~

lI'IO~timportant facior determinh'\9 -theESR. Rou\e.au)!. o~ tne r-e,d blood cells are. 8f~l'c:~e.qmaifl\)1 by \he \Qvels plasma protei.,. levels o~ fibrl~n09"" and 910bulins increase.5 +he. ESR.

'\n. t-AECHANICA\ ANP nc.\-lN!CAL fA CioR S;•.? 1t is im po(~ant "ha\ "h~ FSR.•",be. be 41)(-

ClC\\) pClYptnd·,cl.llar. " ~il! of'3° can cau~C2er-(U1s ~ p -to 'l(J0J• . A l!oo, ~"e raek nCJldif'l9~l'Ie lub~s should neai be. 5ubjec.+ to al\)YYlOV.mfn~ or v·,b~tio~. With IM38 ChC1\'l~es in-\~mpe("tu r4i"tie £S~ \1'lcreClseS·!he '''''-:Itt) andd'orne{er o~ the ~SR {ubf! also ll.Ffec.i- the.~jOClI \esl resvl~s.

'\c.

l)SI\10TIC FRAl;lLlTY TEST ®@Tllll wnll(Jtic Imgility l!~st is llllIPl()y(~d tollllip diugllllSlJ ~liffen~1I1 types uf u\I()\IIias.ill which tlw pliysicldJ2roperties uf tl~lJ redbluud c\~lllIm ;i1tl)l"\)l~l'1H1 maill factor af-

fuelillg tho uSlIIutici frngilitv tost is th!l,~ShH ll! of t u red bloud cell. which. ill turn.I!, { ependonl Oil tllll , () ullleWurface arl)u.lIiid(i)illllctiollnl stulu luI tho rI)J"bl()()d cdL 'liillllllmlllO. All illcro(lsmi uSl1lutic fragilityis iOlllllfill hemolyti\: nllmnins. Iwr(ll\iturysplwrucytosis. nlld whenever splwro,cytesare fuulld. lJocrellsllli usmutic fragilityoccurs followillg splelleclomy. 'ii1 j!iverdisease. sickle coli anemia. iroll,ddi-ci lllley Hllem i 8., t he I !lSSllI Jl in.