acid-base physiology' by kerry brandis
TRANSCRIPT
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'Acid-base pHysiology' by Kerry Brandis
Contents
Chapter 1 : Introduction
1.1 Overview1.2 Acids and Bases1.3 The Hydrogen Ion
1.4 Measurement of H1.! Imortance of H in "e##u#ar Meta$o#ism1.% Imida&o#e A#ha'(tat Hyothesis
Chapter 2 : Control of Acid-Base Balance
2.1 Acid'Base Ba#ance2.2 Buffering2.3 )esiratory )egu#ation
2.4 )ena# )egu#ation2.! The Acid'Base )o#e of the *iver
2.% )egu#ation of Intrace##u#ar +H, -
Chapter 3 : Acid-Base isorders
3.1 Termino#ogy of Acid'Base isorders3.2 Anion /a3.3 The e#ta )atio
3.4 0rinary Anion /a3.! Osmo#ar /a
Chapter ! : "espiratory Acidosis
4.1 efinition4.2 "auses4.3 Maintenance
4.4 Meta$o#ic ffects
4.! "omensation4.% "orrection4. Assessment
4. reventionChapter # : $etabolic Acidosis
!.1 efinition!.2 "auses!.3 Maintenance!.4 Meta$o#ic ffects
!.! "omensation!.% "orrection!. Assessment!. revention
Chapter % : "espiratory Al&alosis
%.1 efinition%.2 "auses%.3 Maintenance%.4 Meta$o#ic ffects
%.! "omensation%.% "orrection%. Assessment%. revention
Chapter : $etabolic Al&alosis
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.1 efinition.2 "auses.3 Maintenance.4 Meta$o#ic ffects
.! "omensation.% "orrection. Assessment. revention
Chapter ( : $a)or *ypes of $etabolic Acidosis
.1 *actic Acidosis.2 5etoacidosis.3 Acidosis and )ena# 6ai#ure.4 Hyerch#oraemic Acidosis
.! )ena# Tu$u#ar Acidosis.% Acidosis due to rugs and To7ins. 0se of Bicar$onate in Meta$o#ic Acidosis
Chapter + : Assess,ent of Acid-Base isorders
8.1 (tructured Aroach to Assessment8.2 (ystematic va#uation8.3 Bedside )u#es to Assess "omensation
8.4 The )ationa#e8.! The /reat Trans'At#antic Acid'Basee$ate8.% "#inica# 7am#es
"ase History Inde7 for wor9ed e7am#es
Chapter 1 : .uantitati/e Acid-Base Analysis
1:.1 The (ystem1:.2 The Bac9ground1:.3 The ;aria$#es
1:.4 The
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*raditional Approach
The discussion of acid'$ase hysio#ogy out#ined in most of this $oo9 is the =traditiona#> emirica#aroach. The concets and e7#anations of this aroach are sti## the most common way that acid'$asehysio#ogy is taught and understood $y many c#inicians.
But this is not the on#y aroach.
hysico-che,ical Approach
An a#ternative aroach derived from hysico'chemica# rinci#es was roosed $y a "anadianhysio#ogist? eter (tewartin 181. A#ternative names for this aroach are the @(tewart aroach@ and@uantitative Acid'$ase Ana#ysis@
The two aroaches are very simi#ar in the way that acid'$ase disorders are c#assified and measured.The maor difference is in the e7#anation and interretation of acid'$ase disorders and contro#mechanisms. )ecent research has #arge#y confirmed the correctness of the (tewart aroach $ut it must$e admitted that it wi## ta9e
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introduction to the E/reat transat#antic acid'$ase de$ateEdiscusses why this aroach is $est.
"hater 1:introduces
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Acid-base hysiology
12 Acids 8 Bases
121 5hat is an acid9
The term is derived from the *atin word =acidus> which means sour. ar#y chemists had a #ist ofroerties that were common to the su$stances that they considered to $e acids or $ases +eg acids had asour taste? turned #itmus red? reacted with some meta#s to roduce a f#amma$#e gas Ghydrogen ..etc.. -.They wou#d assess a new su$stance as an acid or as a $ase Gor as neither $y comaring the roertiesof the new su$stance against the #ist of roerties.
*he Arrhenius *heory
The first modern aroach to acid'$ase chemistry was $yArrheniusin 1. He defined an acid as asu$stance which was caa$#e of dissociating in water so#ution to roduce hydrogen ions. Thisdefinition identified most of the su$stances which were considered to $e acids at that time. A $ase wasdefined as a su$stance which dissociated in water so#ution to roduce hydro7ide ions. The theory was
not tota##y satisfactory for severa# reasons. 6or e7am#e? some su$stances which had acidic roertiesdid not contain hydrogen and some $ases did not contain hydro7ide ions. The theory a#so a#ied on#yto a
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$e accommodated $y considering car$onic acid G H2"O
3 as the acid.
In rea#ity? most hysicians have a $asic 9now#edge of acids and $ases which is somewhat of an
com$ination of the Arrhenius aroach GacidD H,in so#ution? the Bronsted'*owry aroach Gacid Lroton donor and even the *ewis aroach Geg "O2as an acid. This #eve# of understanding is
genera##y satisfactory for c#inica# uroses. The ta$#e $e#ow summarises the different aroaches.
Basic rinciples of the ;arious *heories of Acids and Bases
Traditiona# aroach AcidD a su$stance that has certain roertiesGeg sour taste? turns #itmus red
Arrhenius Acid D H,in a G(tewart and does not e7ist
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in so#utions in that form. This @metahorica# H,@ is e7tensive#y used and this convention is continuedhere.
132 Hydrogen Ion Acti/ity
"hemists sea9 of =idea# so#utions> which have certain redicta$#e hysicochemica# roerties.However? rea# so#utions e7hi$it various degrees of =non'idea#> $ehaviour. This deviation from idea#$ehaviour is due to interactions $etween the mo#ecu#es in the so#ution and inc#udes $oth so#vent'so#uteinteractions and so#ute'so#ute interactions. The magnitude of this interaction Gand the deviation fromidea# $ehaviour is higher with higher artic#e concentration in the so#ution and with ions as comaredto non'charged secies.
The idea of Eeffective concentrationE or EactivityE was introduced $y *ewis to dea# with this ro$#em.Activity indicates how many artic#es seem to $e resent in the so#ution and is different from howmany actua##y are resent. Activity can $e thought of as a#ying a correction factor to theconcentration. Activity is re#ated to concentration $y the activity coefficientD
efinition of Acti/ity
a7L g . +7-
whereDa
7L activity of su$stance 7 in the so#ution
g L activity coefficient of 7+7- L concentration of su$stance 7 in the so#ution
The activity coefficient of a so#ute is constant in any articu#ar given so#ution $ut its va#ue can changeif the roerties of the so#ution are changed Geg $y changing the ionic strength or the temerature. Ifthe re#ationshi $etween concentration and activity is #otted on a grah? it is not #inear. It deends on
the tye of so#vent and the tye and concentration of the various so#utes resent in the so#ution. In anidea# so#ution? the activity coefficient is one. The activity coefficient a#so aroaches unity as non'idea#so#utions $ecome more and more di#ute.
It is usua# in discussions of acid'$ase $a#ance to assume the activity coefficient of so#utes is e
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The a#ternative +H,- is not correct $ecause the activity coefficient is ignored
6ree H,Gie $are rotons are not the form rea##y resent in so#ution anyway.
The disadvantages of H areD
It is a contrived sym$o# which reresents a dou$#e non'#inear transformation of +H,- Gie the #ogof a reciroca#
It is difficu#t to #earn and understand It disguises the magnitude of changes in +H,-
13# A 0i,ple 5ay to Con/ert bet4een pH and
"hanges in the +H,- $y a factor of 2 cause a H change of :.3 'this rovides us with a sim#e way to
determine various H'+H,- airs of va#ues if we 9now that H .4 is 4: nmo#es#. 6or e7am#eD a +H,-of : nmo#es# is a H of .1 ' insection of the ta$#e a$ove shows a va#ue of 8 so this sim#e method
is retty accurate. This usefu# re#ationshi ho#ds $ecause #og 2 is :.3 so a dou$#ing or a ha#ving of +H,-means a change in H $y :.3 either u or down.
"elationship bet4een pH 8
pH
?nano,oles@l
%. 1!
%.8 12!
.: 1::
.1 8
.2 %3
.3 !:
.4 4:
.! 31
.% 2!
. 2:
. 1!
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This doesnEt a##ow you to menta##y ca#cu#ate every H and +H ,- va#ue $ut the 4 $asic airs which areusefu# and easy to memorise areD
H .4 is 4: nM H .: is 1:: nM
H .3% is 44 nM
H .44 is 3% nM
The #ast two va#ues a$ove are the norma# range of H va#ues which is easy to remem$er $ecause the
re#ationshi $etween the +H,- and the decima# art of the H Gie the norma# range of .3% to .44 is a
+H,- range of 44 to 3% nM. Kow you can wor9 out that a H of .:% has a +H,- va#ue of nm as this isdou$#e that at .3% Gie 44nM ' and so on.
"eferences
1.Kor$y P. The origin and meaning of the #itt#e in H. Trends in Biochemica# (ciences 2:::J 2!D 3%'3.
EAcid'$ase Hysio#ogyE $y 5erry Brandis ' from httDwww.anaesthesiaM".com
Acid-Base hysiology
1!: *he $easure,ent of pH
1!1 $ethods
The hydrogen gas #atinum e#ectrode was origina##y used for measuring +H,- $ut is not usefu# forc#inica# H ana#ysis. The sam#e had to $e fu##y saturated with hydrogen gas and a## the o7ygene#iminated. The method is not suita$#e for raid automated ana#ysis of $#ood sam#es. "urrent methodsof H measurement inc#udeD
"o#orimetric methods. *itmus aer is used to decide $etween acid or $ase $ut aersincororating H'sensitive dyes have $een $een designed to measure finer gradations of H Gegurine H is estimated $y use of indicator dyes in distic9s. rogress in co#orimetric Hmethods using indicator dyes Ginc#. f#uorescent dyes has #ead to the deve#oment of accurateintravascu#ar methods of H measurement. The aratrend ,is a commercia##y avai#a$#esystem for measuring intra'arteria# H and $#ood gases.
/#ass e#ectrodes. These are wide#y used in medica# a#ications eg $#ood'gas machines.
I(6T e#ectrodes ' using EIon'se#ective fie#d effect transistorsE. These are used most#y inindustry $ut have $een deve#oed for intravascu#ar use.
http://www.ncbi.nlm.nih.gov/pubmed/10637613?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov/pubmed/10637613?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve%20&%20db=pubmed%20&%20dopt=Abstract%20&%20list_uids=12925481http://www.iscpubs.com/articles/abl/b0201bro.pdfhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve%20&%20db=PubMed%20&%20list_uids=3482477%20&%20dopt=Abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve%20&%20db=PubMed%20&%20list_uids=3482477%20&%20dopt=Abstracthttp://www.ncbi.nlm.nih.gov/pubmed/10637613?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov/pubmed/10637613?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve%20&%20db=pubmed%20&%20dopt=Abstract%20&%20list_uids=12925481http://www.iscpubs.com/articles/abl/b0201bro.pdfhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve%20&%20db=PubMed%20&%20list_uids=3482477%20&%20dopt=Abstract -
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1!2 *he lass pH lectrode
"remer in 18:% discovered that a e#ectrica# otentia# deve#oed across a g#ass mem$rane which wasroortiona# to the H difference across the mem$rane. 5erridge in 182! deve#oed the first g#asse#ectrode for ana#ysis of $#ood sam#es. MacInnesC o#e in 1828 e7erimented with different tyes ofg#ass to find the one which was most sensitive. This MacInnes'o#e g#ass G9nown as "orning :1!g#ass consists of 2Q si#icon dio7ide? %Q ca#cium o7ide and 22Q disodium o7ide GKa
2O.
The H e#ectrode consists of 2 ha#f ce##sD the g#ass e#ectrode and a reference e#ectrode Geg ca#ome#e#ectrode. This unit deve#os an e#ectrica# otentia# across the g#ass which is deendent on the
difference in aH,across the g#ass mem$rane. This effective#y a##ows measurement of the H of the testso#ution $ecause the H in the so#ution on the other side of the mem$rane is constant. Other otentia#sdeve#o in the H e#ectrode Geg #i
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Acid-Base hysiology
1#: pH 8 Cellular $etabolis,
1#1 5hy is pH so i,portant9
*he a/is Hypothesis 8 Ion trapping
hat is the ro#e of H in the $ody and why does H,have an imortance which seems out of 9eeingwith its incredi$#y #ow concentration
An insight can $e gained from the findings of avis G18!. He surveyed a## 9nown meta$o#icathways and #oo9ed at the structura# features of the comounds in each of these athways. He foundthat near#y every =$iosynthetic intermediate has at #east one grou that wou#d $e #arge#y ionised athysio#ogica# H? whether it is an acid or a $ase>. The on#y few e7cetions he cou#d find amongsthundreds of comounds were some macromo#ecu#es? some water'inso#u$#e #iids and end'roducts ofmeta$o#ism Geg waste comounds.
In summary? he found thatD=all 'h (nown low molcular wi)h' and wa'r solu*l *iosyn'h'ic in'rmdia's +ossss )rou+s 'ha'ar ssn'ially com+l'ly ionisd a' nu'ral +-.
These grous are hoshate? ammonium and car$o7y#ic acid grous.
*he a/is hypothesis is that the ad/antage to the cell of this pH-dependent ionisation 4as the
efficient trapping of these ionised co,pounds 4ithin the cell and its organelles
1#2 5hat about the e6ceptions to this generalisation9
There are some comounds that are seeming e7cetions to the genera#isation. (o we need to as9 this
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$y an a#ternative means.
$etabolic precursors 8 4aste products
These comounds need to $e a$#e to cross the mem$rane for ease of uta9e Grecursors #i9e g#ucose ore7cretion Gwaste roducts from the ce##. It is an advantage if they are not charged and not traed. Thefirst reaction that recursors undergo when they enter a ce## is a reaction that #aces a charged grou on
the mo#ecu#e. An e7am#e is g#ucose which is converted to g#ucose'%'hoshate which is charged atintrace##u#ar H and there$y traed within the ce##. "#ear#y any reaction athway that had nonchargedor non'$ound intermediates wou#d have strong evo#utionary ressures against it $ecause of thediffusiona# #oss of these intermediates from the ce##.
(o these e7cetions do not inva#idate the avis hyothesis $ut instead add to it.
The imortance of H,is c#ear#y not re#ated to its concentration er se $ecause this is incredi$#y sma##.Its imortance derives from the fact even though its concentration is e7treme#y #ow? an a#teration in thisconcentration has maor effects on the re#ative concentrations of every conugate acid and $ase of a##the wea9 e#ectro#ytes. One maor conse
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Dirst Hypothesis: pH?ICD E pF
If theoretica##y it is c#ear that the idea# I"6 H shou#d $e the H of neutra#ity GK? then the ne7t ste isto as9 the
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change in temerature. This theory a$out the constancy of the imida&o#e a#ha va#ue as roosed $y)eeves and )ahn has $een termed the imida&o#e a#hastat hyothesis.
A#hastat Hyothesis
The degree of ionisation Ga#ha of the imida&o#e grous ofintrace##u#ar roteins remains constant desite change in
temerature.
The other necessary condition for maintaining imida&o#e a#ha constant is that the "O2content in
$#ood must $e 9et constant at different $ody temeratures. This means that venti#ation must $eregu#ated to maintain the imida&o#e a#ha in the $#ood. It has $een found e7erimenta##y that thisregu#ation to maintain imida&o#e a#ha constant in $#ood wi## resu#t in imida&o#e a#ha $eingmaintained in other comartments Geg intrace##u#ar f#uid as we##. The resiratory contro# that adustsventi#ation ro$a$#y invo#ves roteins whose activity is a#tered in an aroriate direction $y ana#hastat mechanism. Adustment of "6 "O2is necessary as this maintains a constant re#ative
a#9a#inity of the "6 re#ative to the I"6 so there is constancy of the gradient for H ,across the ce##mem$rane. In rea#ity this does not mean that venti#ation has to increase mar9ed#y with decrease intemerature $ecause the reduced meta$o#ic rate wi## automatica##y resu#t in decreased "O
2roduction.
I,portant Fote:Many eo#e have an a#most unsha9ea$#e $e#ief that a H of .: is the Eneutra# HEand conse
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temerature. The resu#ts from the $#ood gas machine must then $e those asmeasured in the machine at 3R". The reference range for 3R" is o$vious#y thecorrect one to a#y when assessing these resu#ts.
Fou shou#d $e carefu# $ecause if you or a co##eague indicate the atientEs actua#temerature on the $#ood'gas re
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A fina# ointD According to chemists? the situation concerning H and temerature is actua##y which must $e ar$itrari#y defined at every temerature. This means that the a$so#uteva#ue of measured otentia# at any articu#ar temerature cannot $e recise#y determined and thus thatH va#ues o$tained at different temeratures? strict#y sea9ing? cannot $e comared. This rea##y is not aconcern to the c#inician.
1%3 6a,ple: Alphastat $anage,ent during Induced Hypother,ia
As a e7am#e? consider the management of a atient who is coo#ed during oen heart surgery.
A atient is coo#ed to 2:R" for cardiac surgery whi#e on cardiac $yass. Imagine an arteria# sam#e wasdrawn and ana#ysed at 2:R" and showed H .%! and "O
21 mmHg. Kow if this same sam#e was
ana#ysed at 3R" then at that temerature? the va#ues wou#d $e H .4 and "O24: mmHg. o which
valu do you wan' r+or'd 'o you1
The va#ues for 3R" can $e interreted against the 9nown reference va#ues for 3R" and they wou#d $e
considered to $e norma#. This is the a#hastat aroach and is e of hydrogen ions rather than the actua# concentration that is imortant for$io#ogica# effects
H is the
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roviding conditions for otima# intrace##u#ar function? articu#ar#yD' intrace##u#ar traing of meta$o#ite intermediates is ma7imised at an intrace##u#ar H ofneutra#ity' activity of a## roteins Ginc# en&ymes is otimised $ecause their net charge is 9et constant
In the $ody? there is strong evidence that intrace##u#ar H changes with temerature such that theintrace##u#ar H remains at or c#ose to the H of neutra#ity. This is achieved $y aroriate
temerature induced changes in the 5 of the imida&o#e grou of histidine. The idea that thedegree of dissociation G9nown as a#ha of imida&o#e remains constant desite changes intemerature is 9nown as the =a#ha'stat hyothesis>. This has im#ications for c#inica# racticeGeg management of hyothermia during cardiou#monary $yass.
E
Acid-Base hysiology
21 - Acid-Base Balance
ach day there is alwaysa roduction of acid $y the $ody>s meta$o#ic rocesses and to maintain$a#ance? these acids need to $e e7creted or meta$o#ised. The various acids roduced $y the $ody arec#assified as resiratory Gor vo#ati#e acids and as meta$o#ic Gor fi7ed acids. The $ody norma##y canresond very effective#y to ertur$ations in acid or $ase roduction.
211 "espiratory Acid
The acid is more correct#y car$onic acid GH2"O
3 $ut the term Eresiratory acidE is usua##y used to mean
car$on dio7ide. But "O2itse#f is not an acid in the Bronsted'*owry system as it does not contain a
hydrogen so cannot $e a roton donor. However "O2can instead $e thought of as reresenting a
otentia# to create an e
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Increased #eve#s of activity wi## increase o7ygen consumtion and car$on dio7ide roduction so thatactua# dai#y "O
2roduction is usua##y significant#y more than the oft' according to the usua# definition. This inconsistency causes
some confusionD it is sim#est to $e aware of this and accet the esta$#ished convention.Ket roduction of fi7ed acids is a$out 1 to 1.! mmo#es of H,er 9i#ogram er dayD a$out : to 1::
mmo#es of H,er day in an adu#t. This non'vo#ati#e acid #oad is e7creted $y the 9idney. 6i7ed acids areroduced due to incom#ete meta$o#ism of car$ohydrates Geg #actate? fats Geg 9etones and rotein Gegsu#hate? hoshate.
The a$ove tota# for net fi7ed acid roduction e7c#udes the #actate roduced $y the $ody each day as themaority of the #actate roduced is meta$o#ised and is not e7creted so there is no net #actate re
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213 "esponse to an Acid-Base erturbation
The $ody>s resonse1to a change in acid'$ase status has three comonentsD
6irst defenceD Buffering
(econd defenceD )esiratory D a#teration in arteria# "O2
Third defenceD )ena# D a#teration in H"O3
' e7cretion
The word EdefenceE is used $ecause these are the three ways that the $ody EdefendsE itse#f against acid'$ase distur$ances. This is not the com#ete icture as it neg#ects some meta$o#ic resonses Geg changesin meta$o#ic athways that occur.
This resonse can $e considered $y #oo9ing at how the comonents affect the G +H"O3- "O2 ratio
in the Henderson'Hasse#$a#ch e
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Most discussions of hydrogen ion $a#ance refers to net roduction Gwhich re
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221 efinition of a Buffer
A $uffer is a so#ution containing su$stances which have the a$i#ity to minimise changes in H when an
acid or $ase is added to it 1.
A $uffer tyica##y consists of a so#ution which contains a wea9 acid HA mi7ed with the sa#t of that acid
C a strong $ase eg KaA. The rinci#e is that the sa#t rovides a reservoir of A'to re#enish +A'- when
A'is removed $y reaction with H,.
222 Buffers in the Body
*he body has a /ery large buffer capacity
This can $e i##ustrated $y considering an o#d e7eriment Gsee $e#ow where di#ute hydroch#oric acidwas infused into a dog.
04an 8 itts 6peri,ent 2
In this e7eriment? dogs received an infusion of 14 mmo#s H,er #itre of $ody water. This causeda dro in H from .44 G+H,- L 3% nmo#es# to a H of .14 G+H,- L 2 nmo#es# That is? a rise in
+H,- of on#y 3% nmo#es#.
(OD If you ust #oo9ed at the change in +H,- then you wou#d on#y notice an increase of 3% nmo#es#and you wou#d have to wonder what had haened to the other 13?888?8%4 nmo#es# that wereinfused.
Where did the missing H+go?
They were hidden on $uffers and so these hydrogen ions were hidden from view.
Before we roceed? #ets ust ma9e sure we areciate what this e7eriment revea#s 3.The dogs were
infused with 14?:::?::: nmo#es# of H,$ut the #asma +H,- on#y changed $y a $it over :.::2Q. By
any ana#ysis? this is a system which po4erfully resists change in . GMy ersona# ana#ogy onareciating the magnitude of this is to use the ana#ogy of deositing V14?:::?::: in the $an9? $ut thenfinding that after E$an9 chargesE my account on#y went u $y V3%.
Ma9e no mista9eD the $ody hasD
a H0/ $uffering caacity? and
this system is essentia##y IMMIAT in effect.
6or these 2 reasons? hysicochemica# $uffering rovides a owerfu# first defence against acid'$aseertur$ations.
Buffering hides fro, /ie4 the real change in H=that occurs
This huge $uffer caacity has another not immediate#y o$vious im#ication for how we thin9 a$out the
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severity of an acid'$ase disorder. Fou wou#d thin9 that the magnitude of an acid'$ase distur$ance cou#d
$e
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Bone "a car$onate In ro#onged meta$o#ic acidosis
223 *he Bicarbonate Buffer 0yste,
The maor $uffer system in the "6 is the "O2'$icar$onate $uffer system. This is resonsi$#e for a$out
:Q of e7trace##u#ar $uffering. It is the most imortant "6 $uffer for meta$o#ic acids $ut it cannot$uffer resiratory acid'$ase disorders.
The comonents are easi#y measured and are re#ated to each other $y the Henderson'Hasse#$a#chea , #og10 G +H"O3- :.:3 7 "O2
The 5>a va#ue is deendent on the temerature? +H,- and the ionic concentration of the so#ution. It hasa va#ue of %.:88 at a temerature of 3" and a #asma H of .4. At a temerature of 3:" and H of
.:? it has a va#ue of %.14. 6or ractica# uroses? a va#ue of %.1 is genera##y assumed and correctionsfor temerature? H of #asma and ionic strength are not used e7cet in recise e7erimenta# wor9.
The 5Ea is derived from the 5a va#ue of the fo##owing reactionD
"O2, H
2O WLX H
2"O
3WLX H,, H"O
3'
Gwhere "O2refers to disso#ved "O
2
The concentration of car$onic acid is very #ow comared to the other comonents so the a$ovee
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H L #og1:G:: ' #og G:.:3 "O2 +H"O
3'-
H L %.1 , #og G +H"O3- :.:3 "O2
On chemica# grounds? a su$stance with a 5a of %.1 shou#d not $e a good $uffer at a H of .4 if itwere a sim#e $uffer. The system is more com#e7 as it is =oen at $oth ends> Gmeaning $oth +H"O
3-
and "O2
can $e adusted and this great#y increases the $uffering effectiveness of this system. The
e7cretion of "O2via the #ungs is articu#ar#y imortant $ecause of the raidity of the resonse. The
adustment of "O2 $y change in a#veo#ar venti#ation has $een referred to as hysio#ogica# $uffering.
*he bicarbonate buffer syste, is an effecti/e buffer syste, despite ha/ing a lo4 pKa because the
body also controls pC2
22! ther Buffers
The other $uffer systems in the $#ood are the rotein and hoshate $uffer systems.
These are the on#y $#ood $uffer systems caa$#e of $uffering resiratory acid'$ase distur$ances as the$icar$onate system is ineffective in $uffering changes in H,roduced $y itse#f.
*he phosphate buffer syste, is F* an i,portant blood buffer as its concentration is too lo4
The concentration of hoshate in the $#ood is so #ow that it is
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imida&o#e grou of the histidine residues which has a 5a of a$out %.. This is suita$#e for effective$uffering at hysio#ogica# H. Haemog#o$in is
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22% "ole of Bone Buffering
*he carbonate and phosphate salts in bone act as a long ter, supply of buffer especially during
prolonged,etabolic acidosis
The imortant ro#e of $one $uffers is often omitted from discussions of acid'$ase hysio#ogy4.
Bone consists of matri7 within which secia#ised ce##s are disersed. The matri7 is comosed oforganic +co##agen and other roteins in ground su$stance- and inorganic +hydro7yaatite crysta#sDgenera# formu#a "a
1:GO
4%GOH
2- comonents. The hydro7yaatite crysta#s ma9e u two'thirds of the
tota# $one vo#ume $ut they are e7treme#y sma## and consearound each of the hydro7yaatite crysta#s. The car$onate is resent in the crysta#s and its re#easere
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$one minera# cannot $e e7#ained $y the acidosis a#one. "hanges in vitamin meta$o#ism? hoshatemeta$o#ism and secondary hyerarathyroidism are more imortant than the acidosis in causing #oss of$one minera# in uraemic atients. The #oss of $one minera# due to these other factors re#easessu$stantia# amounts of $uffer.
0u,,ary
Bone is an imortant source of $uffer in chronic meta$o#ic acidosis Gie rena# tu$u#aracidosis C uraemic acidosis
Bone is ro$a$#y invo#ved in roviding some $uffering Gmost#y $y ionic e7change in mostacute acid'$ase disorders $ut this has $een #itt#e studied.
)e#ease of ca#cium car$onate from $one is the most imortant $uffering mechanisminvo#ved in chronic meta$o#ic acidosis.
*oss of $one crysta# in uraemic acidosis is mu#tifactoria# and acidosis is on#y a minorfactor
BOTH the acidosis and the vitamin 3 changes are resonsi$#e for the osteoma#acia thatoccurs with rena# tu$u#ar acidosis.
"eferences
1. orth#ey *I.ydro)n ion m'a*olism.Anaesth Intensive "are 18 KovJ !G4 34'%:.midD23:14. u$Med
2. itts )6.Mchanisms for s'a*iliin) 'h al(alin rsrvs of 'h *ody.Harvey *ect 18!2'18!3J4 12'2:8. u$Med
3. Bernards "3n'r+r'a'ion of 4linical Acid"5as a'a. )egiona# )efresher "ourses inAnesthesio#ogy. 183J 1D 1'2%
4. Bushins9y A.Acidosis and *on.Miner #ectro#yte Meta$ 1884J 2:G1'2 4:'!2. u$Med
Acid-Base hysiology
23 "espiratory "egulation of Acid-Base Balance
231 Ho4 is the "espiratory 0yste, in&ed to Acid-base Changes9
=)esiratory regu#ation> refers to changes in H due to "O2 changes from a#terations in venti#ation.This change in venti#ation can occur raid#y with significant effects on H. "ar$on dio7ide is #iidso#u$#e and crosses ce## mem$ranes raid#y? so changes in "O2 resu#t in raid changes in +H,- in a##$ody f#uid comartments.
A
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rovide the connection $etween a#veo#ar venti#ation and H via "O2. These 2 re#ationshis areD
6irst e
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9nown.
The ne7t
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Acid-Base hysiology
2! "enal "egulation of Acid-Base Balance
2!1 "ole of the Kidneys
The organs invo#ved in regu#ation of e7terna# acid'$ase $a#ance are the lungsare the &idneys.The #ungs are imortant for e7cretion of car$on dio7ide Gthe resiratory acid and there is a hugeamount of this to $e e7cretedD at #east 12?::: to 13?::: mmo#sday.
In contrast the 9idneys are resonsi$#e for e7cretion of the fi7ed acids and this is a#so a critica# ro#eeven though the amounts invo#ved G:'1:: mmo#sday are much sma##er. The main reason for thisrena# imortance is $ecause there is no other way to e7crete these acids and it shou#d $e areciated
that the amounts invo#ved are sti## very #arge when comared to the #asma +H,- of on#y 4:nanomo#es#itre.
There is a second e7treme#y imortant ro#e that the 9idneys #ay in acid'$ase $a#ance? name#y therea$sortion of the fi#tered $icar$onate. Bicar$onate is the redominant e7trace##u#ar $uffer against the
fi7ed acids and it imortant that its #asma concentration shou#d $e defended against rena# #oss.
In acid'$ase $a#ance? the 9idney is resonsi$#e for 2 maor activitiesD
)ea$sortion of fi#tered $icar$onateD 4?::: to !?::: mmo#day
7cretion of the fi7ed acids Gacid anion and associated H,D a$out 1 mmo#9gday.
Both these rocesses invo#ve secretion of H,into the #umen $y the rena# tu$u#e ce##s $ut on#y the
second #eads to e7cretion of H,from the $ody.
The rena# mechanisms invo#ved in acid'$ase $a#ance can $e difficu#t to understand so as asim+lifica'ionwe wi## consider the rocesses occurring in the 9idney as invo#ving 2 asectsD
ro7ima# tu$u#ar mechanism ista# tu$u#ar mechanism
2!2 ro6i,al *ubular $echanis,
The contri$utions of the ro7ima# tu$u#es to acid'$ase $a#ance areD
first#y? rea$sortion of $icar$onate which is fi#tered at the g#omeru#us
second#y? the roduction of ammonium
The ne7t 2 sections e7#ain these ro#es in more detai#.
2!3 Bicarbonate "eabsorption
ai#y fi#tered $icar$onate e
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and H2O in a reaction cata#ysed $y car$onic anhydrase. The actua# reaction invo#ved is ro$a$#y
formation of H,and OH'from water? then reaction of OH'with "O2Gcata#ysed $y car$onic anhydrase
to roduce H"O3'. ither way? the end resu#t is the same.
The H,#eaves the ro7ima# tu$u#e ce## and enters the "T #umen $y 2 mechanismsD
;ia a Ka,
'H,
antiorter Gmaor route ;ia H,'ATase Groton um
6i#tered H"O3'cannot cross the aica# mem$rane of the "T ce##. Instead it com$ines with the
secreted H,Gunder the inf#uence of $rush $order car$onic anhydrase to roduce "O2and H
2O. The
"O2is #iid so#u$#e and easi#y crosses into the cyto#asm of the "T ce##. In the ce##? it com$ines with
OH'to roduce $icar$onate. The H"O3'crosses the $aso#atera# mem$rane via a Ka,'H"O
3'symorter.
This symorter is e#ectrogenic as it transfers three H"O3
'for every one Ka,. In comarison? the Ka,'
H,antiorter in the aica# mem$rane is not e#ectrogenic $ecause an e can $eoened a #itt#e.
8nc func'ionD The unctions maintain different distri$utions of some of the integra# mem$rane
roteins. 6or e7am#e they act as a =fence> to 9ee the Ka,'H,antiorter #imited to the aica#
mem$rane? and 9ee the Ka,'5,ATase #imited to the $aso#atera# mem$rane. The differentdistri$ution of such roteins is a$so#ute#y essentia# for ce## function.-
The 4 maor factors which contro# $icar$onate rea$sortion areD
*umina# H"O3
'concentration
*umina# f#ow rate
Arteria# "O2
Angiotensin II Gvia decrease in cyc#ic AM
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An increase in any of these four factors causes an increase in $icar$onate rea$sortion. arathyroidhormone a#so has an effectD an increase in hormone #eve# increases cAM and decreases $icar$onaterea$sortion.
utline of "eactions in ro6i,al *ubule u,en 8 Cells
iagram to $e added
The mechanism for H,secretion in the ro7ima# tu$u#e is descri$ed as a high caacity? #ow gradientsystemD
The high caacity refers to the #arge amount G4::: to !::: mmo#s of H,that is secreted er day. GThe
actua# amount of H,secretion is !Q of the fi#tered #oad of H"O3'.
The #ow gradient refers to the #ow H gradient as tu$u#ar H can $e decreased from .4 down to %.'.:on#y.
Though no net e7cretion of H,from the $ody occurs? this ro7ima# mechanism is e7treme#y imortantin acid'$ase $a#ance. *oss of $icar$onate is e
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$e e7creted Gand the hoshate $uffer has $een titrated down.
If H,secretion continues into the medu##ary co##ecting duct this wou#d reduce the H of the #umina#f#uid further. A #ow H great#y augments transfer of ammonium from the medu##ary interstitium into the#umina# f#uid as it asses through the medu##a. The #ower the urine H? the higher the ammoniume7cretion and this ammonium e7cretion is augmented further if an acidosis is resent. Thisaugmentation with acidosis is Eregu#atoryE as the increased ammonium e7cretion $y the 9idney tends to
increase e7trace##u#ar H towards norma#.
If the ammonium returns to the $#ood stream it is meta$o#ised in the #iver to urea G5re$s'Hense#eitcyc#e with net roduction of one hydrogen ion er ammonium mo#ecu#e.
GKoteD (ection 2.4.discusses the ro#e of urinary ammonium e7cretion.
'"enal regulation of Acid-Base Balance' is continued on the ne6t page
Acid-Base hysiology
2! "enal "egulation of Acid-Base Balance ?continued
2!# istal *ubular $echanis,
This is a #ow caacity? high gradient system which accounts for the e7cretion of the dai#y fi7ed acid#oad of : mmo#sday. The ma7ima# caacity of this system is as much as :: mmo#sday $ut this is
sti## #ow comared to the caacity of the ro7ima# tu$u#ar mechanism to secrete H,. It can however
decrease the H down to a #imiting H of a$out 4.! D this reresents a thousand'fo#d Gie 3 H unitsgradient for H,across the dista# tu$u#ar ce##. The ma7ima# caacity of :: mmo#sday ta9es a$out !days to reach.
The rocesses invo#ved areD'
6ormation of titrata$#e acidity GTA
Addition of ammonium GKH4, to #umina# f#uid
)ea$sortion of )emaining Bicar$onate
1 *itratable Acidity
H,is roduced from "O2 and H2O Gas in the ro7ima# tu$u#ar ce##s and active#y transorted into the
dista# tu$u#ar #umen via a H,'ATase um. Titrata$#e acidity reresents the H,which is $ufferedmost#y $y hoshate which is resent in significant concentration. "reatinine G5a aro7 !.: maya#so contri$ute to TA. At the minimum urinary H? it wi## account for some of the titrata$#e acidity. If9etoacids are resent? they a#so contri$ute to titrata$#e acidity. In severe dia$etic 9etoacidosis? $eta'hydro7y$utyrate G5a 4. is the maor comonent of TA.
The TA can $e measured in the urine from the amount of sodium hydro7ide needed to titrate the urineH $ac9 to .4 hence the term =titrata$#e acidity>.
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2 Addition of A,,oniu,
As discussed revious#y? ammonium is redominant#y roduced $y ro7ima# tu$u#ar ce##s. This isadvantageous as the ro7ima# ce##s have access to a high $#ood f#ow in the eritu$u#ar cai##aries and toa## of the fi#trate and these are the two sources of the g#utamine from which the ammonium is roduced.
The medu##ary cyc#ing maintains high medu##ary interstitia# concentrations of ammonium and #owconcentrations of ammonium in the dista# tu$u#e f#uid. The #ower the urine H? the more the amount ofammonium that is transferred from the medu##ary interstitium into the f#uid in the #umen of themedu##ary co##ecting duct as it asses through the medu##a to the rena# e#vis. +KoteD The medu##aryco##ecting duct is different from the dista# convo#uted tu$u#e.-
The net effect of this is that the maority of the ammonium in the fina# urine was transferred from themedu##a across the dista# art of the tu$u#e even though it was roduced in the ro7ima# tu$u#e.+(im#istica##y $ut erroneous#y it is sometimes said that the ammonium in the urine is roduced in thedista# tu$u#e ce##s.-
Ammonium is not measured as art of the titrata$#e acidity $ecause the high 5 of ammonium means
no H,is removed from KH4,during titration to a H of .4. Ammonium e7cretion in severe acidosiscan reach 3:: mmo#day in humans.
Ammonium e7cretion is e7treme#y imortant in increasing acid e7cretion in systemic acidosis. Thetitrata$#e acidity is most#y due to hoshate $uffering and the amount of hoshate resent is #imited$y the amount fi#tered Gand thus the #asma concentration of hoshate. This cannot increasesignificant#y in the resence of acidosis Gthough of course some additiona# hoshate cou#d $e re#easedfrom $one un#ess other anions with a suita$#e 5a are resent. 5etoanions can contri$ute to asignificant increase in titrata$#e acidity $ut on#y in 9etoacidosis when #arge amounts are resent.
In comarison? the amount of ammonium e7cretion can and does increase mar9ed#y in acidosis. Theammonium e7cretion increases as urine H fa##s and a#so this effect is mar9ed#y augmented in acidosis.6ormation of ammonium revents further fa## in H as the 5a of the reaction is so high.
In re/ie4
Titrata$#e acidity is an imortant art of e7cretion of fi7ed acids under norma#circumstances $ut the amount of hoshate avai#a$#e cannot increase very much.
A#so as urine H fa##s? the hoshate wi## $e a## in the dihyrogen form and$uffering $y hoshate wi## $e at its ma7imum.
A further fa## in urine H cannot increase titrata$#e acidity Gun#ess there are otheranions such as 9eto'anions resent in significant
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3 "eabsorption of "e,aining Bicarbonate
On a tyica# estern diet a## of the fi#tered #oad of $icar$onare is rea$sor$ed. The sites and ercentagesof fi#tered $icar$onate invo#ved areD
ro7ima# tu$u#e !Q
Thic9 ascending #im$ of *oo of Hen#e 1:'1!Q
ista# tu$u#e :'!QThe decrease in vo#ume of the fi#trate as further water is removed in the *oo of Hen#e causes anincrease in +H"O3'- in the remaining f#uid. The rocess of H"O3' rea$sortion in the thic9 ascending
#im$ of the *oo of Hen#e is very simi#ar to that in the ro7ima# tu$u#e Gie aica# Ka,'H,antiort and
$aso#atera# Ka,'H"O3' symort and Ka,'5,ATase. Bicar$onate rea$sortion here is stimu#ated $ythe resence of #umina# frusemide. The ce##s in this art of the tu$u#e contain car$onic anhydrase.
Any sma## amount of $icar$onate which enters the dista# tu$u#e can a#so $e rea$sor$ed. The dista#tu$u#e has on#y a #imited caacity to rea$sor$ $icacar$onate so if the fi#tered #oad is high and a #argeamount is de#ivered dista##y then there wi## $e net $icar$onate e7cretion.
The rocess of $icar$onate rea$sortion in the dista# tu$u#e is somewhat different from in the ro7ima#
tu$u#eD
H,secretion $y the interca#ated ce##s in "T invo#ves a H,'ATase Grather than a Ka,'H,
antiort
H"O3' transfer across the $aso#atera# mem$rane invo#ves a H"O3''"#'e7changer Grather than a
Ka,'H"O3' symort
The net effect of the e7cretion of one H,is the return of one H"O3' and one Ka,to the $#ood stream.The H"O3' effective#y re#aces the acid anion which is e7creted in the urine.
The net acid e7cretion in the urine is e
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1 6tracellular /olu,e
;o#ume de#etion is associated with Ka,retention and this a#so enhances H"O3 rea$sortion.
"onverse#y? "6 vo#ume e7ansion resu#ts in rena# Ka,e7cretion and secondary decrease in H"O3rea$sortion.
2 Arterial pC2An increase in arteria# "O2 resu#ts in increased rena# H,secretion and increased $icar$onaterea$sortion. The converse a#so a#ies. Hyercania resu#ts in an intrace##u#ar acidosis and this resu#ts
in enhanced H,secretion. The ce##u#ar rocesses invo#ved have not $een c#ear#y de#ineated. This rena#$icar$onate retention is the rena# comensation for a chronic resiratory acidosis.
3 otassiu, 8 Chloride eficiency
otassium has a ro#e in $icar$onate rea$sortion. *ow intrace##u#ar 5,#eve#s resu#t in increased H"O3
rea$sortion in the 9idney. "h#oride deficiency is e7treme#y imortant in the maintenance of a
meta$o#ic a#9a#osis $ecause it revents e7cretion of the e7cess H"O3 Gie now the $icar$onate insteadof ch#oride is rea$sor$ed with Ka,to maintain e#ectroneutra#ity. G(ee discussion in (ection .3
! Aldosterone 8 cortisol ?hydrocortisone
A#dosterone at norma# #eve#s has no ro#e in rena# regu#ation of acid'$ase $a#ance. A#dosterone de#etion
or e7cess does have indirect effects. High a#dosterone #eve#s resu#t in increased Ka,rea$sortion and
increased urinary e7cretion of H,and 5,resu#ting in a meta$o#ic a#9a#osis. "onverse#y? it might $ethought that hyoa#dosteronism wou#d $e associated with a meta$o#ic acidosis $ut this is veryuncommon $ut may occur if there is coe7istent significant interstitia# rena# disease.
# hosphate 6cretion
hoshate is the maor comonent of titrata$#e acidity. The amount of hoshate resent in the dista#tu$u#e does not vary great#y. "onse
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in urine H and this re#ationshi is mar9ed#y enhanced with acidosis.
2! 5hat is the "ole of 7rinary A,,oniu, 6cretion9
There are different views on the true ro#e of KH4,e7cretion in urine. How can the rena# e7cretion of
ammonium which has a 5 of 8.2 reresent H,e7cretion from the $ody
One schoo# says the roduction of ammonium from g#utamine in the tu$u#e ce##s resu#ts in roductionof a#ha'9etog#utarate which is then meta$o#ised in the tu$u#e ce## to =new> $icar$onate which isreturned to the $#ood. The net effect is the return of one $icar$onate for each ammonium e7creted in theurine. By this ana#ysis? the e7cretion of ammonium is e
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e#inination that has a different acid'$ase effect from urea roduction.
The ro#e of g#utamine is to act as the non'to7ic transort mo#ecu#e to carry KH4,to the 9idney. The$icar$onates consumed in the roduction of g#utamine and then re#eased again with rena# meta$o#ismof 9etog#utarate are not imortant as there is no net gain of $icar$onate.
Overa##D rena# KH4,e7cretion resu#ts indirect#y in an e
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"omment
The a$ove discussion focuses on the Etraditiona#E aroachto acid'$ase $a#ance and ashort'coming of that aroach is that the e7#anations are wrong. The (tewart aroachGsee "hater 1: rovides the e7#anations and the insights into what is occurring. 6or
e7am#e? the focus on e7cretion of H,and e7cretion of KH4,$y the 9idney is
mis#eading. EAcid hand#ingE $y the 9idney is most#y mediated through changes in "#'
$a#ance. KH4
,is a wea9 anion that when e7creted with "#'a##ows the $ody to retain the
strong ions Ka,and 5,. The urinary e7cretion of "#'without e7cretion of an e
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The term acid anion is used $ecause they are anions roduced $y dissociation of an acid.
That isD HA 'X H,, A'Gwhere HA is the acid and A'is the acid anion.
The anions are the conugate $ase of the acid GBronsted'*owry system and are not themse#ves acids.This is an imortant distinction to ma9e $ecause they are often referred to as though they were acidsand this #eads to confusion.
If the endogenous roduction of these anions is fo##owed $y #ater consumtion in the #iver then there isno net roduction of acid or $ase $ecause the H,roduced Gfrom the dissociation of the acid isconsumed when the anion is su$se
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this haened then the $ody wou#d a#so meta$o#ise the endogenous#y roduced #actate and this wou#d$e the maor factor in correction of the acidosis. However? if this heatic meta$o#ism does not haen?then the infused #actate ust interferes with the usefu#ness of seria# #actate measurements as an seria#inde7 of severity of the acidosis.
Overa## then? it is genera##y not the referred "6 re#acement so#ution. If it is the on#y so#ution readi#yavai#a$#e then it can $e used and the infused #actate Ga $ase cannot worsen the acidaemia. The Eofficia#E
recommendation is to not use Hartmann>s so#ution in atients with #actic acidosis. GAs a oint ofinterest? you might #i9e to consider whether norma# sa#ine which contains the non'meta$o#isa$#ech#oride as the anion cou#d ossi$#y $e any $etterU
ndogenous actate
(ome e7cess #actate is norma##y roduced in certain tissues and Esi##s overE into the circu#ation. This#actate can $e ta9en u and meta$o#ised in various tissues Geg myocardium to rovide energy. On#y inthe #iver and the 9idney can the #actate can $e converted $ac9 to g#ucose Gg#uconeogenesis as ana#ternative to meta$o#ism to car$on dio7ide. The g#ucose may re'enter the $#ood and $e ta9en u $yce##s Ges musc#e ce##s. This g#ucose'#actate'g#ucose cyc#ing $etween the tissues is 9nown as the "ori
cyc#e. Tyica##y there is no net #actate roduction which is e7creted from the $ody. The rena# thresho#dfor #actate is re#ative#y high and norma##y a## the fi#tered #actate is rea$sor$ed in the tu$u#es.
The tota# amount of #actate invo#ved is #arge G1?!:: mmo#sday in comarison to the net fi7ed acid
roduction G1 to 1.! mmo#s9gday. The meta$o#ism of #actate in the #iver indirect#y e#iminates the H,
roduced su$se
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Amino acids a#so have side chains and incom#ete meta$o#ism of some of these has acid'$ase effects 'eg side chain meta$o#ism can resu#t in a net fi7ed acid roduction. (u#huric acid is roduced frommeta$o#ism of methionine and cysteine. This is a maor comonent of the net fi7ed acid #oad.
Arginine? #ysine and histidine have nitrogen in their side chains so their meta$o#ism generates H,.
/#utamate and asartate have car$o7y#ic acid grous G"OO' in their side chains so their meta$o#ism
consumes H,Gand therefore roduces H"O3
'. The $a#ance of these reactions is a net dai#y roduction
of H,and acid anions of !: mmo#day Gie roduction of 21: mmo#sday and consumtion of 1%:mmo#day. The #iver is the maor net roducer of fi7ed acids.
2#3 $etabolis, of A,,oniu,
(ee section 2.4for detai#s. The conversion of KH4,to urea in the #iver resu#ts in an e
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2% "egulation of Intracellular Hydrogen Ion Concentration
2%1 I,portance of Intracellular
*he ,ost i,portant for the body is the intracellular
5hy9Because of its rofound effects on meta$o#ism and other ce## rocesses which occur due to theeffects of +H,- on the degree of ionisation of intrace##u#ar comounds. (ecifica##yD
0,all ,olecule effectD Intrace##u#ar traing function'due to the ionisation of meta$o#icintermediates.
arge ,olecule effectD ffects on rotein functionD The function of many intrace##u#ar roteinsGes the activities of en&ymes is a#tered $y effects on the ionisation of amino acid residues Geshistidine residues
In assess,ent of acid-base disordersL the clinician is al4ays loo&ing fro, the outside in
5hy96or 2 reasonsD
ase of sam#ingD Arteria# $#ood is easy to sam#e. It is much more difficu#t to o$tain anintrace##u#ar sam#e
Arteria# $#ood gives resu#ts which can $e considered a sort of Eaverage va#ueE. It wou#d $e moredifficu#t to find an intrace##u#ar sam#e that cou#d $e considered to $e EreresentativeE of a## I"6.
*he basis of the clinical approach is to use the e6tracellular results to ,a&e inferences about
intracellular conditions
Both car$on dio7ide and the fi7ed acids are roduced intrace##u#ar#y and move down concentrationgradients to the "6. "ar$on dio7ide crosses ce## mem$ranes very easi#y and it is imortant to rea#ise
that "O2 can move in or out deending on the gradient across the ce## mem$rane.In dia$etic 9etoacidosisG5A? the 9etoacids are roduced in the #iver and not in every ce## in the$ody. The intrace##u#ar a#9a#inising effect of the comensatory hyocania that occurs wi## howeveraffect every ce## and not ust the heatocytes. oes this mean that 5A roduces an e7trace##u#ar rise
in +H,- $ut the oosite change in most tissues Ge7c#uding the #iver where the net effect is a fa## in
intrace##u#ar +H,- due to the comensatory hyocania 5etoacids can enter most ce##s and $e used as
an energy su$strate and this wou#d initia##y cause a fa## in intrace##u#ar +H,-. Intrace##u#ar H may not$e a#tered much once ma7ima# resiratory comensation has $een achieved $ecause of these oosingeffects. It is ossi$#e that though the ma7ima# resiratory comensation does not fu##y correct thee7trace##u#ar acidaemia? it may $e sufficient to revent much change in intrace##u#ar H. Thisdiscussion is secu#ative and has not $een fu##y investigated. The urose here is mere#y to show that#oo9ing at acid'$ase disorders from the intrace##u#ar viewoint can #ead to ideas which are differentfrom those of the conventiona# e7trace##u#ar viewoint.
The hyothesis of )ahn and cowor9ers Gsee section 1.% is that the intrace##u#ar H is maintained ata$out the H of neutra#ity GK $ecause this is the H at which meta$o#ite intermediates are a## chargedand traed inside the ce##. 7trace##u#ar H is higher $y :.! to :.% H units and this reresents a$out afourfo#d gradient favouring the e7it of hydrogen ion from the ce##. Measurements of intrace##u#ar H ina variety of mamma#ian s9e#eta# musc#e rearations have found H va#ues most#y in the %. to .1range. ;a#ues found in other tissues have sometimes $een higher deending on the e7erimenta#
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arrangements. This va#ue is a #itt#e higher then the K G%. at 3" $ut is sti## a$#e to effective#y traintermediates within the ce##. A further com#ication is that intrace##u#ar H is not uniform andmeasurements have $een a$#e to give on#y mean H va#ues for the who#e intrace##u#ar comartment.These mean va#ues may $e mis#eading as there may $e acidic and $asic areas within different ce## areasor organe##es and it is this #oca# H which is imortant.
Because of the po4erful effects of intracellular on ,etabolis, it is useful to consider theprocesses 4hich atte,pt to ,aintain it at a stable /alue *his assists us in ,a&ing inferences
about intracellular e/ents fro, an e6tracellular acid-base sa,ple
The rocesses resonsi$#e for maintaining a sta$#e intrace##u#ar H areD
=Intrace##u#ar $uffering>
Adustment of arteria# "O2
*oss of fi7ed acids from the ce## into the e7trace##u#ar f#uid
2%2 GIntracellular Buffering
This term refers to those raid reversi$#e rocesses occurring within the intrace##u#ar f#uid whichminimise changes in H in resonse to an acid or a#9a#i stress. The term =$uffering> is used here in amuch $roader sense then that discussed in section 2.2 where it was used to refer to the rocess ofhysicochemica# $uffering a#one. Intrace##u#ar#y? there are other raid and reversi$#e rocesses which
act to minimise acute changes in intrace##u#ar +H,- and which can usefu##y $e considered a form of=$uffering>. =Intrace##u#ar $uffering> inc#udes the fo##owing rocessesD
hysicochemica# $uffering
Meta$o#ic $uffering
Organe##ar $uffering
7eriments have shown that these three rocesses can neutra#ise over 88.88Q of any acid or a#9a#iadded acute#y to the intrace##u#ar f#uidU These rocesses rovide raid $ut temorary re#ief from acuteintrace##u#ar acid'$ase changes.
hysicoche,ical buffering
In
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tend to oose changes in +H,-.
"hanges in intrace##u#ar H affect the activity of en&ymes. The net effect of differentia# changes inen&yme activity in various athways Ginc#uding the main g#yco#ytic athway is an a#teration in the
#eve#s of acidic meta$o#ites in such a way that changes in +H,- are minimised. 6or e7am#e? themeta$o#ism of #actate to g#ucose or to water and "O
2Gwhich can readi#y #eave the ce## wi## effective#y
remove H,
from intrace##u#ar f#uid. This is c#ear#y not sim#y hysicochemica# $uffering. "onsideranother e7am#eD If intrace##u#ar "O2decreases due to acute hyerventi#ation? this roduces a re#ative
intrace##u#ar a#9a#osis. "hanges in en&yme activities resu#t in increased #eve#s of #actate? yruvate andother acidic intermediates. This occurs
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Al&alae,ia ' Arteria# H X .44 Gie +H,- W 3% nM
The meaning of the terms acid? $ase? +H,- and H has $een discussed revious#y in (ections1.2and1.3.
An acidaemia of course must $e due to an acidosis so is an indicator of the resence of this disorder. Inmi7ed acid'$ase disorders? there may $e co'e7isting disorders each having oosite effects on the "6
H so a ?
http://www.anaesthesiamcq.com/AcidBaseBook/ab1_2.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab1_2.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab1_3.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab9_2.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab4_1.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab6_1.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab5_1.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab7_1.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab7_1.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab8_4.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab1_2.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab1_3.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab9_2.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab4_1.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab6_1.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab5_1.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab7_1.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab8_4.php -
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=high> and =norma#> as refera$#e.
313 isorders are defined by their CD ffects
The c#inica# acid'$ase disorders are defined $y their effects in the e7trace##u#ar f#uid Gor moresecifica##y? in the arteria# $#ood.
The disorder may arise $ecause of changes intrace##u#ar#y Geg e7cess #actate roduction $ut the effecte7trace##u#ar#y is what is a$#e to $e easi#y measured.
esite the definitions of acidosis and a#9a#osis a$ove? it is common to sea9 of an Eintrace##u#aracidosisE or an Eintrace##u#ar a#9a#osisE. This use is not consistent with the definitions a$ove $ut as thereare no other satisfactory terms avai#a$#e so this common ractice is fo##owed here.
"eferences
1. Karins )/ and mmett M. im+l and mid acid"*as disordrs: a +rac'ical a++roach.Medicine GBa#timore 18: MayJ !8G3 1%1'. u$Med
2. a#ms#ey )K and hite /H.Mid acid"*as disordrs."#in "hem 18! 6e$J 31G2 321'!.
u$Med3. AdroguY HP.Mid acid"*as dis'ur*ancs.P Kehro# 2::% Mar'ArJ 18 (u# 8 (8'1:3.
u$Med
A## Med#ine a$stractsD u$MedHu$Med
reviousS Inde7S To of ageSKe7t
EAcid'$ase Hysio#ogyE $y 5erry Brandis 'from httDwww.anaesthesiaM".com
Acid-Base hysiology
32 *he Anion ap
321 efinition 8 Clinical 7se
The term anion ga GA/ reresents the concentration of a## the unmeasured anions in the #asma. Thenegative#y charged roteins account for a$out 1:Q of #asma anions and ma9e u the maority of theunmeasured anion reresented $y the anion ga under norma# circumstances. The acid anions Geg#actate? acetoacetate? su#hate roduced during a meta$o#ic acidosis are not measured as art of the
usua# #a$oratory $iochemica# rofi#e. The H,roduced reacts with $icar$onate anions G$uffering andthe "O
2roduced is e7creted via the #ungs Gresiratory comensation. The net effect is a decrease in
the concentration of measured anions Gie H"O3 and an increase in the concentration of unmeasured
anions Gthe acid anions so the anion ga increases.
A/ is ca#cu#ated from the fo##owing formu#aD
Anion ga L +Ka,- ' +"#'- ' +H"O3'-
)eference range is to 1% mmo##. An a#ternative formu#a which inc#udes 5,is sometimes used
articu#ar#y $y Kehro#ogists. In )ena# 0nits? 5,can vary over a wider range and have more effect onthe measured Anion /a. This a#ternative formu#a isD
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6774200http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6774200http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3917878http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16736447http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6774200,3917878,16736447http://www.hubmed.org/display.cgi?uids=6774200,3917878,16736447http://www.anaesthesiamcq.com/AcidBaseBook/ab2_6.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ABindex.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab3_1.php#tophttp://www.anaesthesiamcq.com/AcidBaseBook/ab3_2.phphttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6774200http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3917878http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16736447http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6774200,3917878,16736447http://www.hubmed.org/display.cgi?uids=6774200,3917878,16736447http://www.anaesthesiamcq.com/AcidBaseBook/ab2_6.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ABindex.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab3_1.php#tophttp://www.anaesthesiamcq.com/AcidBaseBook/ab3_2.php -
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A/ L +Ka,- , +5,- ' +"#'- ' +H"O3'-
The reference range is s#ight#y higher with this a#ternative formu#a. The +5,- is #ow re#ative to the otherthree ions and it tyica##y does not change much so omitting it from the et have muchc#inica# significance.
$a)or Clinical 7ses of the Anion ap
To signa# the resence of a meta$o#ic acidosis and confirm other findings
He# differentiate $etween causes of a meta$o#ic acidosisD high anion ga versus norma# anionga meta$o#ic acidosis. In an inorganic meta$o#ic acidosis Geg due H"# infusion? the infused
"#'re#aces H"O3and the anion ga remains norma#. In an organic acidosis? the #ost
$icar$onate is re#aced $y the acid anion which is not norma##y measured. This means that theA/ is increased.
To assist in assessing the $iochemica# severity of the acidosis and fo##ow the resonse totreatment
322 *he Anion ap can be $isleading
It is determined from a ca#cu#ation invo#ving 3 other measured ions? so the error with an A/ is muchhigher than that of a sing#e e#ectro#yte determination. The commonest cause of a #ow anion ga is#a$oratory error in the e#ectro#yte determinations. The 8!Q error range for the A/ is a$out ,' ! mmo##Gie a 1:mmo#s# rangeU
If the A/ is greater than 3: mmo##? than it invaria$#y means that a meta$o#ic acidosis is resent.
If the A/ is in the range 2: to 28 mmo##? than a$out one third of these atients wi## not have ameta$o#ic acidosis.
Other c#inica# guides shou#d a#so $e used in deciding on the resence and severity of a meta$o#ic
acidosis. (ignificant #actic acidosis may $e associated with an anion ga which remains in the referencerange. *actate #eve#s of ! to 1: mmo#s#itre are associated with a high morta#ity if associated withsesis? $ut the A/ may $e reorted as within the reference range in as many as !:Q of these casesUGorwart C "ha#mers 18! G(ee a#so discussion in (ection .4regarding #actate'ch#oride antiort.
The anion ga is usefu# esecia##y if very e#evated or used to confirm other findings. "auses of a highanion ga acidosis can $e sorted out more secifica##y $y using other investigations in addition to thehistory and e7amination of the atient. Investigations which may $e very usefu# areD
*actate
"reatinine
#asma g#ucose
0rine 9etone test
Key Dact: Hypoalbu,inae,ia causes a lo4 anion gap
A#$umin is the maor unmeasured anion and contri$utes a#most the who#e of the va#ue of the anion ga.very one gram decrease in a#$umin wi## decrease anion ga $y 2.! to 3 mmo#es. A norma##y highanion ga acidosis in a atient with hyoa#$uminaemia may aear as a norma# anion ga acidosis.This is articu#ar#y re#evant in Intensive "are atients where #ower a#$umin #eve#s are common. A #acticacidosisin a hyoa#$uminaemic I"0 atient wi## common#y $e associated with a norma# anion ga.
http://www.anaesthesiamcq.com/AcidBaseBook/ab8_4.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab8_1.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab8_1.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab8_4.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab8_1.phphttp://www.anaesthesiamcq.com/AcidBaseBook/ab8_1.php -
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effect wi## $e an increase in unmeasured anions $y the one acid anion A'Gie anion ga increases $yone and a decrease in the $icar$onate $y one.
Kow? if a## the acid dissociated in the "6 and a## the $uffering was $y $icar$onate? then the increase inthe A/ shou#d $e e
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elta "atio Assess,ent uideline
W :.4 Hyerch#oraemic norma# anion ga acidosis
:.4 ' :. "onsider com$ined high A/ C norma# A/ acidosis B0T note that
the ratio is often W1 in acidosis associated with rena# fai#ure
1 to 2 0sua# for uncom#icated high'A/ acidosis*actic acidosisD average va#ue 1.%5A more #i9e#y to have a ratio c#oser to 1 due to urine 9etone #ossGes if atient not dehydrated
X 2 (uggests a re'e7isting e#evated H"O3#eve# so considerD
a concurrent meta$o#ic a#9a#osis? or
a re'e7isting comensated resiratory acidosis
5arning
Be very wary of over'interretation ' A#ways chec9 for other evidence to suort the diagnosis as anune7ected va#ue without any other evidence shou#d a#ways $e treated with great caution.
A high ratio
A high de#ta ratio can occur in the situation where the atient had
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7rinary Anion ap E ? 7A - 7C E = -
3!2 Clinical 7se
Key Dact: *he urinary anion gap can help to differentiate bet4een I* and renal causes of a
hyperchlorae,ic ,etabolic acidosis
It has $een found e7erimenta##y that the 0rinary Anion /a G0A/ rovides a rough inde7 of urinaryammonium e7cretion. Ammonium is ositive#y charged so a rise in its urinary concentration Gieincreased unmeasured cations wi## cause a fa## in 0A/ as can $e areciated $y insection of theformu#a a$ove.
How is this usefu# "onsider the fo##owingD
0tep F: $etabolic acidosis can be di/ided into t4o groups based on the anion gap ?A:
High anion ga acidosis
Korma# anion ga Gor hyerch#oraemic acidosis.
It is easy to ca#cu#ate the anion ga so this differentiation is easy and indeed c#inica##y usefu#.
0tep *4o: Consider the hyperchlorae,ic group for further analysis Hyperchlorae,ic acidosis
can be caused by:
*oss of $ase via the 9idney Geg rena# tu$u#ar acidosis
*oss of $ase via the $owe# Geg diarrhoea.
/ain of minera# acid Geg H"# infusion.
0tep *hree: Bo4el or &idney as the cause9
iagnosis $etween the a$ove 3 grous of causes is usua##y c#inica##y o$vious? $ut occasiona##y it may$e usefu# to have an e7tra aid to he# in deciding $etween a #oss of $ase via the 9idneys or the $owe#.
If the acidosis is due to #oss of $ase via the $owe# then the 9idneys can resonse aroriate#y
$y increasing ammonium e7cretion to cause a net #oss of H,from the $ody. The 0A/ wou#d
tend to $e decreased? That isD increased KH4,Gwith resuma$#y increased "#' LX increased 0"
LXdecreased 0A/.
If the acidosis is due to #oss of $ase via the 9idney? then as the ro$#em is with the 9idney it isnot a$#e to increase ammonium e7cretion and the 0A/ wi## not $e increased.
oes this 4or&9
7erimenta##y? it has $een found that atients with diarrhoea severe enough to cause hyerch#oraemicacidosis have a negative 0A/ Gaverage va#ue '2 ,' 1: mmo## and atients with acidosis due toa#tered urinary acidification had a ositive 0A/. In many cases? the cause Ggut or 9idney wi## $eo$vious? $ut occasiona##y ca#cu#ation of the urinary anion ga can $e usefu#.
3!3 Conclusion
In a atient with a hyerch#oraemic meta$o#ic acidosisD
A negative 0A/ suggests /IT #oss of $icar$onate Geg diarrhoea
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A ositive 0A/ suggests imaired rena# dista# acidification Gie rena# tu$u#ar acidosis.
As a memory aid? remem$er =ne/0Tive> ' negative 0A/ in $owe# causes. 6or more detai#s of the useof the 0A/ in differentiating causes of dista# urinary acidification? see Bat##e et a# G188.
)emem$er that is most cases the diagnosis may $e c#inica##y o$vious Geg severe diarrhoea is hard tomiss and consideration of the urinary anion ga is not necessary.
Acid-Base hysiology
3# - s,olar ap
KBD EOsmo#ar gaE has severa# a#ternative namesD Eosmo# gaE? Eosmo#e gaE? Eosmo#arity gaEC Eosmo#a#gaEJ these a## refer to the same thing. 6or consistency? the term @osmo#ar ga@ is used e7c#usive#ythrough this $oo9.
3#1 5hat is the 'os,olar gap'9
efinitions
An os,oleis the amount of a su$stance that yie#ds? in idea# so#ution?that num$er of artic#es GAvogadro>s num$er that wou#d deress thefree&ing oint of the so#vent $y 1.%5
s,olalityof a so#ution is the num$er of osmo#es of so#ute er9i#ogram of so#vent.
s,olarityof a so#ution is the num$er of osmo#es of so#ute er #itreof so#ution.
(o osmo#a#ity is a measure of the num$er of artic#es resent in a unit weight of so#vent. It isindeendent of the si&e? shae or weight of the artic#es. It can on#y $e measured $y use of a roertyof the so#ution that is deendent on the artic#e concentration. These roerties are co##ective#y referredto as "o##igative roerties. Osmo#a#ity is ,easuredin the #a$oratory $y machines ca##ed osmometers.The units of osmo#a#ity are mOsm9g of so#ute
Osmo#arity is calculatedfrom a formu#a which reresents the so#utes which under ordinarycircumstances contri$ute near#y a## of the osmo#a#ity of the sam#e. There are many such formu#aewhich have $een used. One wide#y used formu#a for #asma which is used at my hosita# isD
Calculated os,olarity E ?1(% 6 = = = +Kote regarding unitsD 6or the a$ove e
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hat #eve# of osmo#ar ga is @a$norma#@
An osmo#ar ga X 1: mOsm# is often stated to $e a$norma#. The suort forthis contention is oor. One study GHoffman )( et a#? 1883 suggested the useof this formu#aD
Calculated os,olarity E ? 2 6 = glucose@1( = B7F@2( =ethanol@!%
They found a mean osmo#ar ga of 2.2 with ( !.! mOsm#. The 8!Q rangeGmean ,' 2( was '14 to ,1:. This study is ro$a$#y the $asis for the X1:va#ue as $eing a$norma#. The range for norma# va#ues is very deendent onthe articu#ar formu#a that is used.
Osmo#arity is easy to ca#cu#ate $ecause it on#y re
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a$norma##y increase the osmo#ar ga. The other tye of osmometer cannot do this. An e7#anation forthis difference isD
@;aor ressure osmometry? in contrast to osmometry using the free&ing oint deression method?re
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A respiratory acidosis is a pri,ary acid-base disorder in 4hich arterial pC2rises to a le/el
higher than e6pected
At onset? the acidosis is designated as an Eacute respiratory acidosisE. The $odyEs initia# comensatoryresonse is #imited during this hase.
As the $odyEs rena# comensatory resonse increases over the ne7t few days? the H returns towardsthe norma# va#ue and the condition is now a Echronic respiratory acidosisE.
The differentiation $etween acute and chronic is determined $y time $ut occurs $ecause of the rena#comensatory resonse Gwhich is s#ow.
Acid-Base hysiology
!2 "espiratory Acidosis - Causes
The arteria# "O2is norma##y maintained at a #eve# of a$out 4: mmHg $y a $a#ance $etween
roduction of "O2$y the $ody and its remova# $y a#veo#ar venti#ation. If the insired gas contains no
"O2then this re#ationshi can $e e7ressed $yD
paC2is proportional to;
C2@ ;
A
whereD
;"O2is "O2roduction $y the $ody;
Ais A#veo#ar venti#ation
An increase in arteria# "O2can occur $y one of three ossi$#e mechanismsD
resence of e7cess "O2in the insired gas
ecreased a#veo#ar venti#ation
Increased roduction of "O2$y the $ody
"O2gas can $e added to the insired gas or it may $e resent $ecause of re$reathing D Anaesthetists are
fami#iar with $oth these mechanisms. In these situations? hyercania can $e induced even in the
resence of norma# a#veo#ar venti#ation and norma# car$on dio7ide roduction $y the $ody.
An adu#t at rest roduces a$out 2::m#s of "O2er minuteD this is e7creted via the #ungs and the arteria#
"O2remains constant. An increased roduction of "O
2wou#d #ead to a resiratory acidosis if
venti#ation remained constant. The system contro##ing arteria# "O2is very efficient Gie raid and
effective and any increase in "O2very romt#y resu#ts in a #arge increase in venti#ation. The resu#t
is that increased "O2roduction a#most never resu#ts in resiratory acidosis. It is on#y in situations
where venti#ation is fi7ed that increased roduction wi## cause resiratory acidosis. 7am#es of this
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wou#d $e a venti#ated atient who deve#os acute ma#ignant hyerthermiaD the arteria# "O2wi## rise
un#ess the a#veo#ar venti#ation is su$stantia##y increased.
$ost cases of respiratory acidosis are due to decreased al/eolar /entilation
The defect #eading to this can occur at any #eve# in the resiratory contro# mechanism. This rovides a
convenient way to c#assify causes that is used in the fo##owing ta$#e.
Al/eolar hypo/entilation ,ay i,pair o6ygen upta&e
The degree of arteria# hyo7aemia wi## $e re#ated to the amount of hyoventi#ation. Increasing theercent of o7ygen in the insired gas can com#ete#y correct the hyo7aemia if hyoventi#ation is theon#y factor invo#ved. If u#monary disease #eading to shunt or venti#ation'erfusion mismatch isresent? then the hyo7aemia wi## not $e so easi#y corrected. The fo##owing #ist c#assifies causes $y themechanism or site causing the resiratory acidosis.
Causes of "espiratory Acidosis ?classified by $echanis,
A: Inadeuate Al/eolar ;entilation
Central Respiratory Depression & Other CNS Problems
rug deression of res. center Geg $y oiates? sedatives? anaesthetics
"K( trauma? infarct? haemorrhage or tumour
Hyoventi#ation of o$esity Geg ic9wic9ian syndrome
"ervica# cord trauma or #esions Gat or a$ove "4 #eve#
High centra# neura# $#oc9ade
o#iomye#itis Tetanus
"ardiac arrest with cere$ra# hyo7ia
Nerve or Musle Disorders
/ui##ain'Barre syndrome
Myasthenia gravis
Musc#e re#a7ant drugs
To7ins eg organohoshates? sna9e venom ;arious myoathies
!ung or Chest Wall De"ets
Acute on "OA
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"hest trauma 'f#ai# chest? contusion? haemothora7
neumothora7
iahragmatic ara#ysis or s#inting
u#monary oedema
Adu#t resiratory distress syndrome
)estrictive #ung disease Asiration
#ir$ay Disorders
0er Airway o$struction
*aryngosasm
BronchosasmAsthma
%ternal 'ators
Inade
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inadequate alveolar ventilation. This is a very imortant oint. Keverthe#ess the rarecauses shou#d $e considered esecia##y in Anaesthetic and Intensive "are ractice where atients areoften intu$ated and connected to circuits. articu#ar issues here inc#udeD
Ma#ignant hyerthermia GMH is an e7treme#y rare $ut otentia##y fata# condition which occursa#most e7c#usive#y in Anaesthetised atients e7osed to certain drugs
;arious circuit misconnections C ma#functions? or soda #ime e7haustion? can resu#t in
significant re$reathing of e7ired car$on dio7ide atients who are ara#ysed and on contro##ed venti#ation cannot increase their a#veo#ar
venti#ation to e7crete any increased amounts of "O2roduced $y the $ody Geg in hyercata$o#ic
states such as sesis or MH
7ogenous car$on dio7ide is introduced into the $ody in certain rocedures Geg #aaroscoyand this increases the amount of car$on dio7ide to $e e7creted $y the #ungs
Adding "O2to the insired gas as a resiratory stimu#ant has resu#ted? a#$eit rare#y? in adverse
outcomes in the ast. GThis ractice is now a$andoned in modern Anaesthetic ractice
"ontinuous canograhy monitoring is now mandatory in Anaesthetic ractice.
Acid-Base hysiology
!3 "espiratory Acidosis - $aintenance
Key Dact: A rise in arterial pC2is a potent sti,ulus to /entilation so a respiratory acidosis 4ill
rapidly correct unless so,e abnor,al factor is ,aintaining the hypo/entilation
This feed$ac9 mechanism is resonsi$#e for the norma# tight contro# of arteria# "O2. The factorcausing the disorder is a#so the factor maintaining it. The revai#ing arteria# "O
2reresents the
$a#ance $etween the effects of the rimary cause and the resiratory stimu#ation due to the increased"O
2.
Other then $y venti#atory assistance? the "O2wi## return to norma# on#y $y correction of the cause of
the decreased a#veo#ar venti#ation.
An e7treme#y high arteria# "O2has direct anaesthetic effects and this wi## #ead to a worsening of the
situation either $y centra# deression of venti#ation or as a resu#t of #oss of airway atency orrotection.
Acid-Base hysiology
!! "espiratory Acidosis - $etabolic ffects
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!!1 epression of Intracellular $etabolis,
As C2rapidly and easily crosses lipid barriersL a respiratory acidosis has rapid 8 generally
depressing effects on intracellular ,etabolis,
Hyercania wi## raid#y cause an intrace##u#ar acidosis in a## ce##s in the $ody. The c#inica# icture wi##
$e affected $y the arteria# hyo7aemia that is usua##y resent. The effects descri$ed $e#ow are themeta$o#ic effects of hyercania rather than resiratory acidosis. atients with resiratory acidosis can$e hyocanic if a severe meta$o#ic acidosis is a#so resent.
Imortant effects of Hyercania
(timu#ation of venti#ation via $oth centra# and erihera# chemorecetors
"ere$ra# vasodi#ation increasing cere$ra# $#ood f#ow and intracrania# ressure
(timu#ation of the symathetic nervous system resu#ting in tachycardia? erihera#vasoconstriction and sweating
erihera# vasodi#ation $y direct effect on vesse#s
"entra# deression at very high #eve#s of "O2
!!2 I,portance of Cerebral ffects
*he cerebral effects of hypercapnia are usually the ,ost i,portant
These effects areD
increased cere$ra# $#ood f#ow?
increased intracrania# ressure? C
otent stimu#ation of venti#ation.
This can resu#t in dysnoea? disorientation? acute confusion? headache? menta# o$tundation or evenfoca# neuro#ogic signs. atients with mar9ed e#evations of arteria# "O
2may $e comatose $ut severa#
factors contri$ute to thisD
Anaesthetic effects of very high arteria# "O2Geg X 1::mmHg
Arteria# hyo7aemia
Increased intracrania# ressure
As a ractica# c#inica# e7am#e? the rise in intracrania# ressure due to hyercania may $e articu#ar#ymar9ed in atients with intracrania# atho#ogy Geg tumours? head inury as the usua# comensatorymechanism of "(6 trans#ocation may $e readi#y e7hausted. Any associated hyo7aemia wi## contri$uteto an adverse outcome.
!!3 ffects on Cardio/ascular 0yste,
*he effects on the cardio/ascular syste, are a balance bet4een the direct and indirect effects
Tyica##y? the atient is warm? f#ushed? sweaty? tachycardic and has a $ouncing u#se.
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!#1 *he co,pensatory response is a rise in the bicarbonate le/el
This rise has an immediate comonent Gdue to a resetting of the hysicochemica# e
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H"O3that #eaves the ce## causes the rise in e7trace##u#ar H"O
3. The amount of $uffering is #imited $y
the concentration of rotein as that is #ow re#ative to the amount of car$on dio7ide re
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0cenario 2
If a atient with chronic resiratory acidosis is intu$ated and venti#ated? the arteria# "O2can $e
raid#y corrected G$y adusting the venti#ator arameters. This can occur is a $eneficia# strategy. The idea is to adust venti#ation to a##ow ade
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!%2 5hat is Gpost hypercapnic al&alosis9
The correction of the e#evated $icar$onate Grena# comensation associated with chronic resiratoryacidosis may not $e raid. )eturn of #asma $icar$onate to norma# re
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The reason we have to a##ow for a meta$o#ic acid'$ase disorder is that the "O2va#ue changes from
4:mmHg due so#e#y to the $odyEs comensatory venti#atory resonse to a meta$o#ic acidosis ora#9a#osis so ust using a va#ue of 4:mmHg as norma# wou#d $e wrong and #ead us to incorrectconc#usions.
ith an acute meta$o#ic acidosis? the $ody resonds $y increasing a#veo#ar venti#ation. This resonse iscomensatory $ecause hyerventi#ation resu#ts in a decrease in arteria# "O
2
which tends to return the
arteria# H towards .4+ar'ially correcting the acute deviation of #asma H from norma#. The va#ue of"O
2at ma7ima# comensation can $e redicted using a sim#e $edside Eru#e of thum$E and this
ca#cu#ated va#ue is the Ee7ectedE "O2which we use to comare with the Eactua#EGmeasured "O
2
va#ue.
If a meta$o#ic disorder is resent? we can ca#cu#ate Gusing a sim#e formu#a a new reference va#ue of"O
2G the =e7ected "O
2> that we wou#d e7ect that wou#d $e resent with tyica# #eve#s of
resiratory comensation. e use this ca#cu#ated Ee7ected va#ueE to comare with the actua# measuredva#ue.
Fou wi## now note as a conse
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hyerventi#ation that occurs with a meta$o#ic acidosis $ut this term is
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A ,etabolic acidosis is an abnor,al pri,ary process or condition leading to an increase in fi6ed
acids in the blood
This causes the arteria# #asma $icar$onate to fa## to a #eve# #ower than e7ected. The fa## in #asma
$icar$onate is due to titration of H"O3
'$y H,.
0econdary or co,pensatory processeswhich cause a fa## in #asma $icar$onate shou#d not $econfused with rimary rocesses. A fa## in $icar$onate occurring in resonse to a chronic resiratorya#9a#osis shou#d $e referred to as a comensatory resonse and never as a =secondary meta$o#icacidosis>.
This distinction $etween a rimary rocess and a secondary one has $een discussed revious#y insection 3.1.2when discussing termino#ogy of acid'$ase disorders.
It is of course ossi$#e for a atient to have a mi7ed acid'$ase