introduction to acid base disorders

8/11/2019 Introduction to Acid Base Disorders

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Acid Base Abnormalities

This teaching module will provide an overview of acid base abnormalities. Below is a list of topics that will be covered:

Introduction to Acid Base Disturbances and Definitions

Compensatory Responses

Calculations: Anion Gap, Delta Ratio, Urine Anion Gap, Osmolar Gap

Step by Step Approach to interpretin an arterial blood as

!hysiolo ic "ffects of Acid Base Disorders

"tiolo y of Acid Base Disorders

Introduction to Acid Base Disorders

In order to approach acid base disorders, consider the following equations:

1) #enderson #asselbalch e$uation : p# % &'( ) lo *#CO+ -. /'/+ !CO0

where 6.1 is the p a !negative logarithm of the acid dissociation constant) for carbonic acid !"#$%&) and '.'&, the factor whichrelates ($%# to the amount of $%# dissolved in plasma.

#) 1assirer Bleich e$uation : *#)- % 02 3 !CO0 . *#CO+ -

p# *#)-, nanomol.45'6/ (&5'5/ 0/

5'&/ 0&5'7/ +05'2/ 2/5'+/ 7/5'0/ &+5'(/ 6/5'// (//&'8/ (07&'6/ (&/

lthough cumbersome and somewhat difficult to use at the bedside, both equations represent a ver* important relationship. The*predict that the ratio of dissol9ed CO0 to #CO+ , rather than their actual concentrations, determines h*drogen ion concentrationand thus p".

drop or rise in ($%# will result in a drop or rise in +" - respectivel*.

+"$%& - on the other hand is inversel* related to " concentration whereb* a drop in bicarbonate levels result in an increase in "concentration while a rise in bicarbonate levels result in a reduction in " concentration.

This buffer s*stem is of ph*siologic importance because both the pulmonar* and renal mechanisms for regulating p" wor/ b*ad0usting this ratio.

The ($%# can be modified b* changes in alveolar ventilation, while plasma +"$%& - can be altered b* regulating its generationand e cretion b* the /idne*s.

Definitions

An acid base disorder is a change in the normal value of extracellular pH that may result when renal or respiratory function isabnormal or when an acid or base load overwhelms excretory capacity.

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ormal acid base 9alues

p# !CO0 #CO+2ange: 3.&4 3.54 &6 55 ## #6%ptimal value 3.5' 5' #5

Acid base status is defined in terms of the plasma pH.

Acidemia decrease in the blood p" below normal range of 3.&4 3.54

Al;alemia levation in blood p" above the normal range of 3.&4 7 3.54

Clinical disturbances of acid base metabolism classically are defined in terms of theHCO3- /CO2 buffer system.

Acidosis < process that increases +" - b* increasing ($%# or b* reducing +"$%& -Al;alosis < process that reduces +" - b* reducing ($%# or b* increasing +"$%& -

It is important to note that thou h acidosis and al;alosis usually leads to acidemia and al;alemia respecti9ely, thee=ception occurs >hen there is a mi=ed acid base disorder' In that situation, multiple acid base processes coe=istin maylead to a normal p# or a mi=ed picture' ?his >ill be discussed in more detail later'

8ince ($%# is regulated b* respiration, abnormalities that primaril* alter the ($%# are referred to as respiratory acidosis !high($%#) and respiratory al;alosis !low ($%#).

In contrast, +"$%& - is regulated primaril* b* renal processes. bnormalities that primaril* alter the +"$%& - are referred to asmetabolic acidosis !low +"$%& -) and metabolic al;alosis !high +"$%& -).

Simple acid base disorders : 9isorders that are either metabolic or respirator*.

@i=ed acid base disoders : ore than one acid base disturbance present. p" ma* be normal or abnormal.

Compensatory Responses

cid Base disoders are associated with defense mechanisms referred to as compensator* responses that function to reduce theeffects of the particular disorder on the p". They do not restore the pH back to a normal value . This can onl* be done with correctionof the underl*ing cause. In each of these disorders, compensator* renal or respirator* responses act to minimi;e the change in "concentration b* minimi;ing the alteration in the ($%#


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In general, respiratory compensation results in a .2 mmHg reduction in !CO2 for e"ery .# me$/% reduction in the plasma HCO3- concentration do&n to a minimum !CO2 of # to 'mmHg '

@or e ample, if an acid load lowers the plasma "$%& concentration to A meq, then:9egree of "$%& reduction is #5 !optimal value) 7 A ? 14.Therefore, ($%# reduction should be 14 1.# ? 1C.Then ($%# measured should be 5' !optimal value) 7 1C ? ##mm"g.

inter s EormulaTo estimate the e pected ($%# range based on respirator* compensation, one can also use the DinterEs @ormula which predicts:!CO0 % ('7 3 *#CO+ - ) 6 F 0

Therefore in the above e ample, the ($%# according to DinterEs should be!1.4 A) C F # ? #' #5

nother useful tool in estimating the ($%# in metabolic acidosis is the recognition that the pCO0 is al>ays appro=imately e$ualto the last 0 di its of the p#'

Compensatory Responses: Respiratory Acidosis

2espirator* cidosis is an acid base disturbance characteri;ed b* an elevation in the partial pressure of dissolved $%# leading toan elevation in the ($%#


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If the ($%# is acutel* increased to C' mm"g, there will be appro imatel* a 5meq elevation in the plasma +"$%& - to #C meqand a potentiall* serious reduction in e tracellular p" to 3.13.

$hange in ($%# ? C' 5' ? 5'.Therefore elevation in +"$%& - ? 5'


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Acute Respiratory Al;alosis

bout 1' minutes after the onset of respirator* al/alosis, h*drogen ions move from the cells into the e tracellular fluid, where the*combine with +"$% & to form carbonic acid in the following reaction:" "$% & H " #$% & !$ )

The h*drogen ions are primaril* derived from intracellular buffers such as hemoglobin, protein and phosphates. The reaction withbicarbonate ions in this reaction leads to a mild reduction in plasma +"$% & -.

In acute respiratory al alosis, as a result of cell buffering, for e"ery # mmHg decrease in the !CO2, there is a 2me$/%decrease in the plasma HCO3- concentration.

(lease note that the cellular buffering does not offer adequate protection against respirator* al/alosis. @or e ample:

If the ($%#, were reduced to #' mm"g, the change in ($%# would be #' !5' #') and therefore the fall in plasma +"$%& - wouldbe 5 meq !#'


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!rimary disorderInitial

chemicalchan e

Compensatoryresponse Compensatory @echanism "=pected le9el of compensation

@etabolicAcidosis #CO+ !CO0 #yper9entilation

!CO0 % ('7 3 *#CO+ - ) 6F 0

!CO0 % ('0 3H *#CO+ -

!CO0 % last 0 di its of p#

@etabolicAl;alosis #CO+ !CO0 #ypo9entilation

!CO0 % /'8 3 *#CO+ - ) (& F 0

!CO0 % /'5 3 H *#CO+ -

RespiratoryAcidosis !CO0 #CO+

Acute Intracellular Bufferin hemo lobin,intracellular proteins*#CO+ - % ( m"$.4 for e9ery (/

mm # H!CO0

Chronic Generation of ne> #CO+ due to the increasede=cretion of ammonium'*#CO+ - % +'7 m"$.4 for e9ery (/

mm # H!CO0

RespiratoryAl;alosis !CO0 #CO+

Acute Intracellular Bufferin *#CO+ - % 0 m"$.4 for e9ery (/mm # H!CO0

Chronic Decreased reabsorption of #CO+ , decreasede=cretion of ammonium*#CO+ - %2 m"$.4 for e9ery (/

mm # H!CO0

lso: In acute respirator* acidosis, Jp" ? '.''C K ($%#In chronic respirator* acidosis, Jp" ? '.''& K ($%#.

Calculations

There are various calculations that are commonl* used diagnosticall* in interpreting acid base disorders and distinguishingbetween different causes of acid base disorders. $alculating the anion gap is an approach that must be ta/en in all cases ofmetabolic acidosis. %ther calculations such as osmolar gap and urine anion gap, are used when clinicall*, the cause of an acidbase disorder is in doubt.

This teaching module will discuss the various diagnostic calculations that can be useful in interpreting acid base disorders.mphasis will be placed on the underl*ing rational behind each formula to increase comprehension and deduction and minimi;e

memori;ation.

Topics to be covered are:

nion Lap 9elta 2atio

Grine nion Lap

%smolar Lap

Anion Gap Dhen acid is added to the bod*, the +" - increases and the +"$%& - decreases. In addition, the concentration of the

anion, which is associated with the acid, increases. This change in the anion concentration provides a convenient wa* toanal*;e and help determine the cause of a metabolic acidosis b* calculating what is termed the anion ap .

The anion gap is estimated b* subtracting the sum of $l and "$%& concentrations from the plasma a concentration. a Gnmeasured cations ? Cl ) #CO+ ) Gnmeasured anions Anion ap % * a- < *Cl - ) *#CO+ - The ma0or unmeasured cations are calcium, magnesium, gamma globulins and potassium. The ma0or unmeasured anions

are negativel* charged plasma proteins !albumin), sulphate, phosphates, lactate and other organic anions. The anion gapis defined as the quantit* of anions not balanced b* cations. This is usuall* equal to 1# F 5 meq and is usuall* due to thene ati9ely char ed plasma proteins as the charges of the other unmeasured cations and anions tend to balance out.

If the anion of the acid added to plasma is $l , the anion gap will be normal !i.e., the decrease in +"$%& - is matched b*an increase in +$l -). @or e ample:#Cl ) a#CO+ J aCl ) #0CO+ J CO0 ) #0O

In this setting, there is a meq. for meq. replacement of e tracellular "$%& b* $l = thus, there is no change in the anion

gap, since the sum of $l - +"$%& - remains constant. This disorder is called a h*perchloremic acidosis, because of theassociated increase in the $l concentration. LI or renal loss of "$%& produces the same effect as adding "$l as the/idne* in its effort to preserve the $M will retain a$l leading to a net e change of lost "$%& for $l .

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In contrast, if the anion of the acid is not $l !e.g. lactate, N h*dro *but*rate), the anion gap will increase !i.e. the decreasein +"$%& - is not matched b* an increase in the +$l - but rather b* an increase in the +unmeasured anion-:#A ) a#CO+ J aA ) #0CO+ J CO0 ) #0O , where is the unmeasured anion.

$auses of elevated nion gap acidosis is best remembered b* the mnemonic 1U4? or the popular @UD!I4"S

@ ? ethanolU ? GremiaD ? 9 !also and starvation)! ? (araldeh*deI ? I "4 ? >actic acidosis" ? th*lene Ll*colS ? 8al*cilate

1 ? etoacidosis !9 ,alcoholic /etoacidosis,starvation)U ? Gremia !2enal @ailure)4 ?>actic acidosis? ? To ins ! th*lene gl*col, methanol, paraldeh*de,salic*late)

Because, ne ati9ely char ed plasma proteins account for the normal anion ap, the normal 9alues shouldbe adKusted do>n>ard for patients >ith hypoalbuminemia'

?he appro=imate correction is a reduction in the normal anion ap of 0'7 me$.l for e9ery ( .dl decline in theplasma albumin concentration normal 9alue % 2 .dl '

8ee practice case C for an e ample. ?he Delta Ratio H.H The delta ratio is sometimes used in the assessment of elevated anion gap metabolic acidosis to determine if a mi ed acid

base disorder is present. Delta ratio % H Anion ap.H *#CO+ - or Oanion ap. J *#CO+ - Delta Delta % @easured anion ap < ormal anion ap Delta del ormal *#CO+ - < @easured *#CO+ - 9elta 9elta % AG < (0 Delta delaaa 02 *#CO+ - In order to understand this, let us re e amine the concept of the anion gap. If one molecule of metabolic acid !" ) is added to the $@ and dissociates, the one " released will react with one

molecule of "$%& to produce $%# and "#%. This is the process of buffering. ?he net effect >ill be an increase inunmeasured anions by the one acid anion A ie anion ap increases by one and a decrease in the bicarbonateby one me$'

ow, if all the acid dissociated in the $@ and all the buffering was b* bicarbonate, then the increase in the L should beequal to the decrease in bicarbonate so the ratio between these two changes !which we call the delta ratio) should beequal to one.

s described previousl*, more than 4'P of e cess acid is buffered intracellularl* and b* bone, not b* "$%& . In contrast,most of the e cess anions remain in the $@, because anions cannot easil* cross the lipid bila*er of the cell membrane.As a result, the ele9ation in the anion ap usually e=ceeds the fall in the plasma *#CO+ -' In lactic acidosis, fore=ample, the H.H ratio a9era es ('&:( .

On the other hand, althou h the same principle applies to ;etoacidosis, the ratio is usually close to (:( in thisdisorder because the loss of /etoacids anions !/etones) lowers the anion gap and tends to balance the effect ofintracellular buffering. nion loss in the urine is much less prominent in lactic acidosis because the associated state ofmar/ed tissue h*poperfusion usuall* results in little or no urine output.

delta delta value below 1:1 indicates a greater fall in +"$%& - than one would e pect given the increase in the aniongap. This can be e plained b* a mi ed metabolic acidosis, i.e a combined elevated anion gap acidosis and a normal aniongap acidosis, as might occur when lactic acidosis is superimposed on severe diarrhea. In this situation, the additional fallin "$%& is due to further buffering of an acid that does not contribute to the anion gap. !i.e addition of "$l to the bod* asa result of diarrhea)

value above #:1 indicates a lesser fall in +"$%& - than one would e pect given the change in the anion gap. This can bee plained b* another process that increases the +"$%& -,i.e. a concurrent metabolic al/alosis. nother situation toconsider is a pre e isting high "$%& level as would be seen in chronic respirator* acidosis.

Delta ratio Assessment Guidelines

L /'2#yperchloremic normal anion ap acidosis

L ( #i h AG M normal AG acidosis

( to 0 !ure Anion Gap Acidosis4actic acidosis: a9era e 9alue ('&D1A more li;ely to ha9e a ratio closer to ( due to urine ;etone loss

N 0 #i h AG acidosis and a concurrent metabolic al;alosis

or a pre e=istin compensated respiratory acidosis

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8ee case & and 3 for e amples.

Urine Anion Gap

The three main causes of normal anion gap acidosis are:

>oss of "$%& from Lastrointestinal tract !diarrhea) >oss of "$%& from the idne*s !2T s)

dministration of acid

9istinguishing between the above & groups of causes is usuall* clinicall* obvious, but occasionall* it ma* be useful to have ane tra aid to help in deciding between a loss of base via the /idne*s or the bowel. $alculation of the urine anion ap ma* be helpfuldiagnosticall* in these cases.

The measured cations and anions in the urine are a , , and $l = thus the urine anion gap is equal to:Grine anion gap ? * a)- ) *1)- *Cl -Grine anion gap ? unmeasured anions 7 unmeasured cations

In normal sub0ects, the urine anion gap is usuall* near ;ero or is positive ' In metabolic acidosis, the e cretion of the "5 !which ise creted with $l ) should increase mar/edl* if renal acidification is intact. Because of the rise in urinar* $l , the urine anion gapwhich is also called the urinary net char e , becomes negative, ranging from #' to more than 4' meq. The negative valueoccurs because the $l concentration now e ceeds the sum total of a and .

In contrast, if there is an impairment in /idne* function resulting in an inabilit* to increase ammonium e cretion !i.e. 2enal Tubular cidosis), then $l ions will not be increased in the urine and the urine anion gap will not be affected and will be positive or ;ero.

In a patient with a h*perchloremic metabolic acidosis: A ne ati9e UAG su ests GI loss of bicarbonate e diarrhea , apositi9e UAG su ests impaired renal acidification ie renal tubular acidosis '

s a memor* aid, remember Qne GU? iveR negative G L in bowel causes.

2emember that in most cases the diagnosis ma* be clinicall* obvious !severe diarrhea is hard to miss) and consideration of theurinar* anion gap is not necessar*.

8ee case 4 for an e ample.

%smolar Lap

The %smolar Lap is another important diagnostic tool that can be used in differentiating the causes of elevated anion gapmetabolic acidosis. The ma0or osmotic particles in plasma are a , $l , "$%& , urea and glucose and as such, plasma osmolarit*can be estimated as follows:!lasma osmolarity % 0 a ) lucose.(6 ) BU .0'6

ote that because $l and "$%& are alwa*s bound to a, their contributions to osmolarit* are estimated b* doubling the aconcentration. (lasma osmolalit* !(osm) can also be measured directl* b* free;ing point depression. The osmolar gap is thedifference between the calculated serum osmolarit* and the measured serum osmolarit*.

Osmolar Gap % @easured !osm < Calculated !osm

The normal osmolar gap is 1' 14 mmol "#' .The osmolar gap is increased in the presence of low molecular weight substancesthat are not included in the formula for calculating plasma osmolarit*. $ommon substances that increase the osmolar gap areethanol, ethylene lycol, methanol, acetone, isopropyl ethanol and propylene lycol'

In a patient suspected of poisoning, a high osmolar gap particularly if 0 2'1 &ith an other&ise une plained highanion gap metabolic acidosis is suggesti"e of either methanol or ethylene glycol into ication.

%ne must correlate an elevated osmolar gap with other clinical findings because it is a relativel* nonspecific finding that is alsocommonl* seen in alcoholic and diabetic /etoacidosis, lactic acidosis and in chronic renal failure. levation in the osmolar gap inthese disease states is thought to be due in part to elevations of endogenous gl*cerol, acetone, acetone metabolites, and in thecase of renal failure, retention of unidentified small solutes.

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Step>ise approach to interpretin the arterial blood as'

( . #M!' The most clinical useful information comes from the clinical description of the patient b* the histor* and ph*sicale amination. The "S( usuall* gives an idea of what acid base disorder might be present even before collecting the BL sample

0. 4oo; at the p# . Is there an acid base disorder present If p" U 3.&4, then acidemia if p" V 3.54, then al/alemia If p" within normal range, then acid base disorder not li/el* present. p" ma* be normal in the presence of a mi ed acid base disorder, particularl* if other parameters of the BL are abnormal.

+. 4oo; at !CO0, #CO+ ' Dhat is the acid base process !al/alosis vs acidosis) leading to the abnormal p" re both valuesnormal or abnormal

In simple acid base disorders, both values are abnormal and direction of the abnormal change is the same for both parameters. %ne abnormal value will be the initial change and the other will be the compensator* response.

+a . Distin uish the initial chan e from the compensatory response'The initial change will be the abnormal value that correlates with the abnormal p". If l/alosis, then ($%# low or "$%& high If cidosis, then ($%# high or "$%& low.

%nce the initial change is identified, then the other abnormal parameter is the compensator* response if the direction of the changeis the same. If not, suspect a mi ed disorder.

+b . %nce the initial chemical change and the compensator* response is distinguished, then identify the specific disorder . 8eetable below.

If ($%# is the initial chemical change, then process is respirator*. if "$%& is the initial chemical change, then process is metabolic.

Acid Base Disorder Initial Chemical Chan e Compensatory Response

Respiratory Acidosis !CO0 #CO+

Respiratory Al;alosis !CO0 #CO+

@etabolic Acidosis #CO+ !CO0

@etabolic Al;alosis #CO+ !CO0

2. If respiratory process, is it acute or chronic n acute respirator* process will produce a compensator* response that is due primaril* to rapid intracellular buffering. chronic respirator* process will produce a more significant compensator* response that is due primaril* to renal adaptation,

which ta/es a longer time to develop. To assess if acute or chronic, determine the e=tent of compensation. 8ee table .

7. If metabolic acidosis, then loo/ at the Anion Gap . If elevated !V than 16), then acidosis due to G>T. ! etoacidosis, Gremia, >actic acidosis, To ins). 8ee table . If anion gap is normal, then acidosis li/el* due to diarrhea, 2T .

&. If metabolic process, is degree of compensation ade$uate $alculate the estimated ($%#, this will help to determine if a seperate respirator* disorder is present. 8ee table .

5. If anion gap is elevated, then calculate the Delta Ratio !K


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!hysiolo ic "ffects of Acidosis

Respiratory "ffects

#yper9entilation 1ussmaul respirations

Shift of o=yhaemo lobin dissociation cur9e to the ri ht

Decreases 0,+ D!G le9els in red cells, >hich opposes the effect abo9e' shifts theODC bac; to the left ?his effect occurs after & hours of acidemia '

Cardio9ascular "ffects

Depression of myocardial contractility this effect predominates at p# L 5'0

Sympathetic o9er acti9ity tachycardia, 9asoconstriction, decreased arrhythmia

threshold

Resistance to the effects of catecholamines occur >hen acidemia 9ery se9ere

!eripheral arteriolar 9asodilatation

Penoconstriction of peripheral 9eins

Pasoconstriction of pulmonary arteries

"ffects of hyper;alemia on heart

Central er9ous System "ffects

Cerebral 9asodilation leads to an increase in cerebral blood flo> and intracranialpressure occur in acute respiratory acidosis

Pery hi h pCo0 le9els >ill cause central depression

Other "ffects

Increased bone resorption chronic metabolic acidosis only

Shift of 1) out of cells causin hyper;alemia an effect seen particularly inmetabolic acidosis and only >hen caused by non or anic acids

Increase in e=tracellular phosphate concentration

!hysiolo ic "ffects of Al;alosis

Respiratory "ffects

Shift of o=yhaemo lobin dissociation cur9e to the left impaired unloadin ofo=y en

?he abo9e effect is ho>e9er balanced by an increase in 0,+ D!G le9els in RBCs'

Inhibition of respiratory dri9e 9ia the central M peripheral chemoreceptors

Cardio9ascular "ffects

Depression of myocardial contractility

ArrhythmiasCentral er9ous System "ffects

Cerebral 9asoconstriction leads to a decrease in cerebral blood flo> result in

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confusion, muoclonus, asteri=is, loss of consciousness and seiQures Onlyseen in acute respiratory al;alosis' "ffect last only about & hours'

Increased neuromuscular e=citability resultin in paraesthesias such ascircumoral tin lin M numbness carpopedal spasm Seen particularly in acuterespiratory al;alosis'

Other "ffects

Causes shift of hydro en ions into cells, leadin to hypo;alemia'

ote: ost of the above effects are short lasting.

"tiolo y of Acid Base Disturbances

This teaching module will give an overview of common causes of specific acid base disoders. lso included are conditions or scenarios thatcommonl* lead to mi ed acid base disorders.

etabolic cidosis etabolic l/alosis

2espirator* cidosis

2espirator* l/alosis

i ed cid Base 9isorders

@etabolic Acidosis

A primary metabolic acidosis is characteri ed by lo& arterial pH 4 +.3'1, reduced plasma HCO3- concentration,and compensatory al"eolar hyper"entilation resulting in decreased !CO2.

It can be induced b* either increased endogenous acid production, increased e ogenous acid administration, loss of "$%& , orb* decreased abilit* to e crete the normal dietar* " load.

Differential Dia nosis

The differential diagnosis of metabolic acidosis is vast and is best approached if one brea/s down the causes of metabolicacidosis into normal vs elevated anion ap metabolic acidosis. 8ee below.

"le9ated Anion Gap N(& me$ ormal Anion Gap 6 (& me$

Increased "ndo enous production :

1etoacidosis Alcohol, S tar9ation,D1A

4actic Acidosis

Uremia

4oss of Bicarbonate :DiarrheaCarbonic anhydrase inhibitors?ype 0 R?A pro=imal!ancreatic ileostomy!ancreatic, biliary, intestinal fistula

"=o enous Administration :ammonium chloride or #C4

Decreased Renal Acid "=cretion :?ype ( distal ,2 R?ARenal Eailure

Into=ications :@ethanol, "thylene Glycol,!araldehyde, Salicylates, I #

@iscellaneous :#yper;alemiaReco9ery from D1A

Clic; submenu or ne=t for select causes of metabolic acidosis

4actic Acidosis

commonl* encountered cause of elevated anion gap metabolic acidosis, particularl* in the I$G is lactic acid. >actic acidosis ischaracteri;ed b* a p" U 3.&6 and lactate level V 7mmol.4

>actic acid is produced under normal aerobic states in cells of the brain, retina, and er*throc*tes. Gnder normal circumstances,

lactate is circulated to the liver, and to a lesser degree the /idne*, where it is converted into glucose or $%# and "#% .

4actate ) +O0 J #CO+ ) 0CO0 ) 0#0O0 4actate ) 0CO0 ) 0#0O J 0#CO+ ) lucose'

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http://fitsweb.uchc.edu/student/selectives/TimurGraham/Etiology_Metabolic_Acidosis.htmlhttp://fitsweb.uchc.edu/student/selectives/TimurGraham/Etiology_Metabolic_Alkalosis.htmlhttp://fitsweb.uchc.edu/student/selectives/TimurGraham/Etiology_Respiratory_Acidosis.htmlhttp://fitsweb.uchc.edu/student/selectives/TimurGraham/Etiology_Respiratory_Alkalosis.htmlhttp://fitsweb.uchc.edu/student/selectives/TimurGraham/Mixed_Acid_Base_Disorders.htmlhttp://fitsweb.uchc.edu/student/selectives/TimurGraham/Mixed_Acid_Base_Disorders.htmlhttp://fitsweb.uchc.edu/student/selectives/TimurGraham/Etiology_Metabolic_Acidosis.htmlhttp://fitsweb.uchc.edu/student/selectives/TimurGraham/Etiology_Metabolic_Alkalosis.htmlhttp://fitsweb.uchc.edu/student/selectives/TimurGraham/Etiology_Respiratory_Acidosis.htmlhttp://fitsweb.uchc.edu/student/selectives/TimurGraham/Etiology_Respiratory_Alkalosis.htmlhttp://fitsweb.uchc.edu/student/selectives/TimurGraham/Mixed_Acid_Base_Disorders.html


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In h*po ic states !low %# suppl*) such as in strenuous muscle activit* !sei;ure) or in low tissue perfusion states from circulator*failure, lactic acid is also produced anaerobicall* during gl*col*sis. This occurs via the following reaction:

This conversion of p*ruvate to lactate in anaerobic conditions is promoted b* the accumulation of 9" and the depletion of 9which is needed as an electron acceptor so that gl*col*sis can continue. The conversion to lactate results in the regeneration of

9 so that minimal amounts of T( can be made indefinitel* from gl*col*sis in states of ver* low tissue o *genation.

>actate accumulation and lactic acidosis results because in states of low tissue perfusion such as shoc/, or in states ofmitochondrion d*sfunction, lactate cannot be rec*cled to the liver for conversion bac/ to glucose or for further brea/down becauseboth of these reactions as shown above require o *gen and both ta/e place in the mitochondrion.

There are primaril* # t*pes of lactic acidosis:

?ype A 7 9ue to tissue h*poperfusion and h*po ia?ype B 7 ot due to tissue h*poperfusion and h*po ia.

?ype A 4actic Acidosisost cases of lactic acidosis are due to reduced o *gen deliver* as a result of reduced tissue perfusion from shoc; or

cardiopulmonar* arrest. %ther conditions such as acute pulmonary edema , can cause severe h*po emia leading to reduced %#deliver*. %ther causes are carbon mono ide poisoning and se9ere anemia . %ther causes of t*pe lactic acidosis which ma* notnecessaril* involve generali;ed tissue h*po ia are se9ere seiQure , se9ere e=erciQe and hypothermic shi9erin . ll of whichresult in locali;ed s/eletal muscle h*po ia leading to increased lactic acid production.

The clinical signs usuall* indicate reduced tissue perfusion and include severe h*potension, tach*pnea, oliguria or anuria,peripheral vasoconstriction and deteriorating mental status. Sepsis , particularl* in criticall* ill patients is a ver* important cause oflactic acidosis and is often associated with fever !V&C.4W$) or h*pothermia !&4W$). 1ussmaul hyper9entilation !deep sighing

respiration) ma* be observed if the severit* of the acidosis is sufficient to elicit a degree of respirator* compensation. >acticacidosis is usuall* associated with laborator* abnormalities indicating organ failure or compromise such as abnormal liver functiontests, elevated BG and elevated creatinine. >actate levels are usuall* greater than 4 meq. Gpper limit of nl is 1.6 in plasma.

nion gap is classicall* elevated, V 16.

?ype B 4actic AcidosisGsuall* without clinicall* apparent tissue h*po ia and can be due to an* number of conditions:

Gnderl*ing diseases: 9 , uremia, liver disease, infections, malignancies 9rugs and to ins: ethanol, methanol, eth*lene gl*col, salic*lates, metformin

Inborn errors of metabolism: p*ruvate deh*drogenase deficienc*, gl*cogen storage disease, p*ruvate carbo *lasedeficienc*, etc.

%ther : D 4actic acidosis !short bowel s*ndrome) X, idiopathic

T*pical picture includes acute onset after nausea and vomiting, altered state of consciousness and h*perventilation. >aborator*findings are variable depending on underl*ing cause.

D 4actic Acidosis Xasil* missed diagnosis, because the isomer responsible for the acidosis is the 9 isomer which is not detected b* the standard

assa* for lactate. This unique form of lactic acidosis can occur in patients with KeKunoilelal bypass , or less commonl*, small bo>elresectio n or other causes of the short bo>el syndrome'

In these settings, the glucose and starch are metaboli;ed in the colon into 9 lactic acid, which is then absorbed into the s*stemiccirculation. The ensuing acidemia tends to persist, since 9 lactate is not recogni;ed b* > lactate deh*drogenase, the en;*me that

catal*;es the conversion of the ph*siologicall* occurring > lactate into p*ruvate.

12


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Two factors that tend to contribute to the accumulation of 9 lactate s*stemicall* are 1) an o9er ro>th of ram positi9eanaerobes , such as lactobacilli that are most able to produce 9 lactate and #) increased deli9ery of lucose and starch to thecolon in the presence of a shorter small bo>el transit'

(atients t*picall* present with recurring episodes of metabolic acidosis, usuall* after a carboh*drate meal, and characteristicneurologic abnormalities including confusion, cerebella ata ia, slurred speech, and loss of memor*.

Criteria for D lactic acidosis:

(resence of short bowel s*ndrome with an intact colon. n acute episode of encephalopathic s*mptoms, such as confusion, slurred speech , ata ia, unstead* gait, abusive

behavior and lactate levels

8erum 9 lactate levels V & mmom

bnormal colonic flora, with a predominance of Lram positive anaerobic bacteria !>actobacilli, which produce largeamounts of lactic acid)

?reatment for 4actic AcidosisTreatment of lactic acidosis requires identification of the primar* illness and therap* directed toward correction of that disturbance.2estoration of tissue o *gen deliver* through hemod*namic and


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Gncontrolled t*pe 1 diabetes mellitus is the most common cause of /etoacidosis. The lac/ of insulin contributes to this condition notonl* via decreased glucose upta/e but also b* promoting lipol*sis !trigl*ceride brea/down) and fatt* acid o idation. It is a state thatalso includes an increase in counter re ulatory hormones !ie, glucagon, cortisol, growth hormone, epinephrine) which contributeto h*pergl*cemia b* promoting further gluconeogenesis and to /etonemia b* promoting acet*l 7$% migration into mitochondrionwhere the* can be converted into /etones.

(rogressive rise of blood concentration of these acidic organic substances initiall* leads to a state of /etonemia. atural bod*buffers can buffer /etonemia in its earl* stages. Dhen the accumulated /etones e ceed the bod*Es capacit* of e tracting them,the* overflow into urine !ie, /etonuria). If the situation is not treated promptl*, more accumulation of organic acids leads to fran/clinical metabolic acidosis !ie, /etoacidosis), with a drop in p" and bicarbonate serum levels. "*pergl*cemia usuall* e ceeds the

renal threshold of glucose absorption and results in significant gl*cosuria. $onsequentl*, water loss in the urine is increased!pol*uria) due to osmotic diuresis induced b* gl*cosuria. This incidence of increased water loss results in severe deh*dration, thirst,tissue h*poperfusion, and, possibl*, lactic acidosis. In addition, beta h*dro *but*rate induces nausea and vomiting thatconsequentl* aggravate fluid loss. ?ypical free >ater loss in D1A is appro=imately & liters or nearl* 1'' m>


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nion gap V 16

8erum normal, high or low.

8erum a low phos low.

8erum phosphate: usuall* phosphate depleted due to urine losses but are normal or high b* labs due to transcellularshift out of cells in the setting of acidosis and insulin deficienc*. After treatment >ith Insulin, phosphate le9els usuallylo>

8erum glucose usuall* V &'' mg


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These patients frequentl* ma* present with a mi ed acid base disturbance:

levated anion gap metabolic acidosis secondar* to etoacidosis etabolic al/alosis as a result of persistent vomiting

$hronic respirator* al/alosis as a result of liver disease.

ild degree of lactic acidosis ma* also be present, contributing to the elevated anion gap acidosis.

"istor*

$hronic alcoholic who goes on drin/ing binge 9evelops pancreatitis, gastritis, which leads to abdominal pain, nausea and persistent vomiting

8*mptoms leads to cessation of alcohol consumption and poor oral inta/e 1 to & da*s prior to presentation

8*mptoms ma* also include that of liver disease or portal h*pertension : melena, hematoche;ia, hematemesis, fatigue,d*spnea

lcoholic withdrawal: tremors, sei;ure, hallucinations, delirium tremens

8igns

Tach*cardia, tach*pnea, ussmaul respiration, h*potension !possibl*) bdominal tenderness !particularl* if pancreatitis present)

"eme positive stools

(h*sical e am findings ma* include that of chronic liver disease: spider nevi, ascitis, hepatomegal*, caput medusa,palmar er*thema, varices, 0aundice, g*necomastia

>aborator* findings

BL: p" ma* be low high or normal depending on acid base disturbances present. ($%# will be low, "$%& high. niongap will be elevated, V16 8erum /etones ma* be falsel* negative, or onl* wea/l* positive.

8erum glucose ma* be low, normal or onl* slightl* elevated !in contrast to 9 were glucose levels are significantl*elevated)

8erum lactate ma* be elevated

g, phos, depleted low due to increased urinar* e cretion and poor nutrition. (hos ma* appear normal or high due totranscellular shift in the setting of acidosis.

Bun and $r elevated due to prerenal a otemia

nemia ma* be present due to alcohol induced bone marrow suppression, h*perspenism, or LI bleed

"ct ma* be falsel* elevated due hemoconcentration secondar* to volume loss.

lcohol levels absent or low

>@Ts ma* be abnormal if liver disease present. m*lase, lipase elevated if pancreatitis present

?reatment

stablish B$s. If the patientEs mental status is diminished, consider administration of o *gen, thiamine, de trose, andnalo one. 2emember thiamine must be given prior to de trose to prevent Dernic/e orsa/off.

%nce the diagnosis of is established, the mainsta* of treatment is h*dration with 4P de trose in normal saline!94 8.) $arboh*drate and fluid replacement reverse the pathoph*siologic derangements that lead to b* increasingserum insulin levels and suppressing the release of glucagons and other counter regulator* hormones. 9e trose

16


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stimulates the o idation of 9" and aids in normali;ing the 9"< 9 ratio. @luids alone do not correct asquic/l* as fluids and carboh*drates together.

Insulin contraindicated, because ma* lead to life threatening h*pogl*cemia particularl* as the patientRs endogenous insulinlevels rise with carboh*drate and fluid repletion.

Bicarbonate onl* given if p" U 3.1, and acidosis not responding to IM@.

Star9ation. Eastin

8tarvation, as mentioned previousl* can result in /etoacidosis due to the increase in counter regulator* hormones and a decreasein insulin, a balance which promotes fatt* acid o idation, gluconeogenesis, and /etone production.

"owever in comparison to the potentiall* severe /etoacidosis that develops in uncontrolled diabetes and alcoholic states, /etoacidlevels do not e ceed 1' meq with fasting. This limitation in the /etone formation ma* reflect the abilit* of /etonemia to promoteinsulin secretion, eventuall* limiting the release of free fatt* acids and thus /etoacidosis

Renal ?ubular Acidosis

Renal Tubular Acidosis (RTA) refer to a group of disorders intrinsic to renal tubules characterized by an impairment in urinary acidificationwhich result in retention of H+ ions, reduction in plasma [H !"#$ and a hyperchloremic metabolic acidosis with a normal serum anion gap%There are " distinct types of RTA, each ha&ing a different pathophysiology leading to decreased acid e'cretion% The urinary anion gap ([ a + $

* l# ) is usually positi&e in RTA due to an inability to e'crete H+ % This distinguishes RTA from the other causes of normal anion gap metabolicacidosis such as diarrhea which will ha&e a negati&e urinary anion gap%

Clic; ne=t or submenu for a discussion on each type of R?A'

?ype ( Distal R?A

T*pe 1 or distal 2T is referred to as the classic 2T and is a disorder of acid e cretion involving the collectin tubules . Thedisorder is characteri;ed b* a hypo;alemic, hyperchloremic metabolic acidosis .

(athoph*siolog*

The disorder is due to defective " ion secretion in the distal tubule. Impairment in #) ions secretion result in an inability to

acidify the p# beyond 7'7 which retards the e cretion of titratable acids !" #(% 5) and " 5 ions, thus resulting in a reduction in netacid e cretion. The plasma bicarbonate is significantl* reduced and ma* fall below (/ me$.4'

The impairment in " ions secretion is most commonl* thought to be due to a defect in the luminal #) A?!ase pump located inthe intercalating cells of the collecting tubule. The " T(ase pump is primaril* responsible for the h*drogen secretion in the distalnephrons.

These patients tend to have urinar* wasting and h*po/alemia. The etiolog* of the h*po/alemia is unclear but is thought to bedue to increased potassium secretion b* distal tubular cells in the setting of diminished " ion secretion.

"*percalciuria, h*perphosphatemia, nephrolithiasis !calcium phosphate stones) and nephrocalcinosis are fre$uently associated>ith untreated type ( R?A' The h*percalciuria is thought to be due to 1) increased calcium phosphate release from bone as aresult of bone buffering of e cess acid and #) reduction in tubular calcium reabsorption secondar* to chronic acidosis. Theh*percalciuria, al/aline urine, and reduced e cretion of citrate in the urine !which normall* prevents calcium cr*stalli;ation) promotethe precipitation of calcium phosphate and stone formation. The h*pocitraturia is thought to be due to the effects of acidosis andh*po/alemia on pro imal tubule reabsorption.

$auses

an* different conditions have been associated with t*pe I 2T . 8ee table below. The most common identifiable causes in adultsare autoimmune disorders, such as SKo renTs syndrome . In children, 2T is most often a primar* hereditar* condition.

8*mptoms

?he loss of calcium salts from bones in these patients can result in failure to thri9e, ric;ets and stuntin of ro>th inchildren and osteomalacia or osteopenia in adults . (atients ma* otherwise be as*mptomatic or ma* present with s*mptoms ofsevere acidosis or h*po/alemia !pol*uria, pol*d*psia, wea/ness and fatigue)

17


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@aKor causes of distal R?A

Idiopathic or sporadic in children

EamilialAutosomal dominantAutosomal recessi9e

Secondary Ac$uiredSKo ren s

#ypercalciuriaRheumatoid Arthritis , S4"#yper lobulinemiaIfosfamide, Amphotericin , 4ithium carbonateSic;le cell anemiaCirrhosis, renal transplant

?ype 0 !ro=imal R?A

T*pe # 2T is characteri;ed b* an impairment in pro=imal #CO+ reabsorption resulting in a hypo;alemic hyperchloremic metabolicacidosis'

(athoph*siolog*

This condition usuall* appears as part of a generali;ed disorder of pro imal tubular function /nown as Eanconi syndrome which alsoinclude defects in the absorption of glucose, amino acids, phosphate, uric acid, and other organic anions such as citrate.

The reduction in "$%& reabsorption leads to an increase in bicarbonate loss in the urine. 2emember that a loss of a single bicarbonateion is a/in to adding one h*drogen ion to the plasma, therefore this bicarbonate loss in the urine leads to increased h*drogen ionconcentration and a subsequent reduction in arterial p".

Gsuall* about A'P of the filtered "$%& is absorbed b* the pro imal tubule, the rest is absorbed b* the distal nephrons. In the setting ofpro imal impairment of "$%& , the dis tal nephrons become overwhelmed b* an increase in "$%& deliver* and cannot compensate forthe loss in pro imal function. "owever as urinar* "$%& loss progresses, plasma "$%& drops to 14 1C meq. This causes the level offiltered "$%& to fall and thus there is reduced deliver* of "$%& ions to the distal nephrons. t that point, the distal nephrons are nolonger overwhelmed and can regain function, leading to a reduction in bicarbonaturia and a urine which can now be acidic. This is incontrast to t*pe 1 2T , where urine acidification is limited to a minimum urinar* p" of 4.4.

?hus type 0 R?A is a self limitin disorder in >hich the plasma #CO+ concentration is usually bet>een (2 and 0/ me$.4due to the establishment of a ne> steady state '

Grinar* wasting and h*po/alemia are common in t*pe # 2T and is due to persistent hyperaldosteronism, leading to increased secretion b* the distal nephrons. "*peraldosteronism in these patients are related to the defect in pro imal reabsorption of filtered "$%&which in effect leads to decreased pro imal a$l reabsorption and a tendenc* for salt wasting.

The factors responsible for the defects in pro imal transport are incompletel* understood. There are three features of the pro imal tubulesthat are vital to pro imal reabsorption of "$%& : 1) the a) #) e=chan er in the luminal membrane, #) the a) 1) A?!Ase pump inthe basolateral membrane and &) the enQyme carbonic anhydrase, which is located both intracellularl* where it results in the generationof " and "$%& , and in the lumen, where it facilitates "$%& reabsorption. It has been proposed that one or more of these factors mustbe impaired to account for the defect in t*pe # 2T .

$auses

Below is a table showing some of the /nown causes of t*pe II 2T . variet* of congenital and acquired disorders can cause t*pe # 2T .Idiopathic 2T and c*stinosis are most common in children= carbonic anhydrase inhibitors and multiple myeloma are most oftenresponsible in adults.

$omplications

s in t*pe 1 2T , bone disease also occurs due to an increase in bone buffering of e cess acid and the release of calcium salts from bone.Also contributin to this problem is ac$uired 9itamin D deficiency, since the pro=imal tubule is a maKor site of formation ofcalcitriol'

9efects in pro imal transport ma* also result in phosphate wasting and hypophosphatemia leading to decreased deposition of mineral inbone. 2ic/ets in children and osteomalacia or osteopenia in adults are relativel* common in t*pe # 2T , occurring in up to #'P of cases.

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In contrast to t*pe 1 2T , nephrocalcinosis and nephrolithiasis does not occur , and this is due to normal levels of urinar* cit rate in thiscondition !in contrast to t*pe #) and the abilit* to acidif* the urine which increases the solubilit* of calcium phosphate.

@aKor Causes of type 0 R?A

Idiopathic or sporadic in children

#ereditaryA' CystinosisB' GalactosemiaC' ?yrosinemiaD' Glyco en stora e disease, type ("' ilson s disease

Ac$uired disordersA' @ultiple @yelomaB' #ypocalcemia and 9itamin D deficiencyC' Dru s and ?o=ins: AcetaQolamide or other carbonic anhydrase inhibitor,Ifosfamide, StreptoQocin, 4ead, Cadmium, @ercury, outdated tetracyclineD' Amyloidosis"' Renal transplant reKection

?ype 2 R?A

T*pe IM 2T is the onl* t*pe characteri;ed b* a hyper;alemic, hyperchloremic acidosis . The defect is thought to beAldosterone deficiency or resistance'

(athoph*siolog*

ldosterone deficienc* or resistance impairs the secretion of h*drogen and potassium ion resulting in acidosis and hyper;alemia .The h*per/alemia is usuall* ver* prominent in this condition and has an important role in metabolic acidosis b* impairingammonium production and acid e cretion in the urine. The h*per/alemia in this setting impairs "5 production in the pro imaltubule b* inducing a state of intracellular al;alosis within the tubular cell. This occurs due to the transcellular e change ofpotassium for h*drogen resulting in the e it of h*drogen ion from the cell.

The development of intracellular al/alosis reduces "5 secretion b* the pro imal tubular, which in combination with decreasedh*drogen secretion distall*, result in decreased ammonium e cretion and decreased net acid e cretion. 2eversing this process b*correcting the h*per/alemia often leads to increased "5 e cretion and correction of the metabolic acidosis

The metabolic acidosis seen with h*poaldosteronism is generall* mild, with the plasma +"$%& - usually abo9e (7 me$.4 . Despitethe impairment in distal #) secretion, the urine p# in this disorder is enerally but not al>ays belo> 7'+ , in contrast to t*pe1 2T . The abilit* to acidif* the urine in this condition is due to the inadequate amount of "& available for buffering of protons.

ven if onl* a few protons are secreted distall*, urinar* p" will fall in the absence of buffers. This is in contrast to t*pe 1 2T wheredistal " secretion is impaired and an* protons secreted will be buffered b* available "& , thus maintaining an al/aline urine.

$auses

T*pe 5 2T due to aldosterone deficienc* has multiple etiologies. #yporeninemic hypoaldosteronism is the most common causeand is usuall* asscoiated with mild to moderate renal insufficenc*. It is most commonl* found in diabetes nephropathy andchronic interstitial nephritis . 8 I98, $ inhibitors, trimetoprim and heparin can all reduce aldosterone production andproduce a t*pe 5 2T . 9rug induced t*pe 5 2T is usuall* seen in patients with pre e isting renal insufficienc*.

(atients with tubular resistance to aldosterone will present ver* similarl* to h*poreninemic h*poaldosteronism. It is thought to bedue to a tubulointerstial process that damages the distal tubule causing retention of h*drogen and potassium ions despite adequatealdosterone. B!# and sic;le cell disease are the most common causes. Spironolactone has also been /nown to cause analdosterone resistant state.

8*mptoms

T*pe IM 2T is usuall* as*mptomatic with onl* mild acidosis, but cardiac arrh*thmias or paral*sis ma* develop if h*per/alemia ise treme.

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Dia nosis of R?A

T*pe I 2T

The findings of h*po/alemic, normal anion gap metabolic acidosis with an inappropriately hi h urine p# N7'7 and postive urineanion gap confirm the diagnosis ' In patients with a normal plasma bicarbonate concentration, the failure to lower urinar* p" to lessthan 4.4 after an acute acid challenge with "5$l defines the s*ndrome of incomplete classic distal R?A

T*pe II 2T

The diagnosis of t*pe # 2T is made b* measurement of the urine p" and fractional bicarbonate e cretion during a bicarbonateinfusion.The plasma bicarbonate concentration is raised toward normal !1C #' meq) with an intravenous infusion of sodiumbicarbonate at a rate of '.4 to 1.' meq


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T*pe # 2T

l/ali therap* is required for normal growth in children and to prevent or treat osteopenia


22/41

%ral al/ali is t*picall* used to maintain the +"$%& - over #' meq. This can be accomplished with relativel* modest amounts ofal/ali !1.' to 1.4 m q and lesser concentration of $>. ach meq of " ion secretedgenerates 1 meq of "$%& which is then absorbed in the plasma. Gnder normal conditions the increase in the plasma "$%&concentration is onl* transient, since the entr* of acid into the duodenum stimulates an equal amount of "$%& secretion from the

pancreas. "owever there is no stimulus to "$%& secretion if gastric 0uice is removed during vomiting and L suction. The netresult is an increase in the plasma +"$%& - and metabolic al/alosis.

22

(' 4oss of hydro en ions fromGI

0' "=o enous addition ofal;ali

+' ?ranscellular #) shift

2' Contraction al;alosis

(' Reduced "CP < decreased GERand increased absorption of #CO+

0' #ypo;alemia

(' @ineralocorticoid e=cess

0' Se9ere #ypo;alemia

#ypo;alemia


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Gnder normal conditions, the e cess "$%& generated would be e creted in the urine b* the /idne* and thus al/alosis would notbe maintained. "owever vomiting or nasogastric suction also results in a decrease in the e tracellular f luid compartment and theeffective circulating volume ! $M). The reduction in the $M leads to decreased L@2 !less bicarb filtered), and also serves as astimulus to increase angiotensin and aldosterone production leading to an increase in a and "$%& reabsorption b* the pro imaltubules. n increase in a reabsorption leads to increased "$%& reabsorption because of the increase in h*drogen secretion as

a is e changed for " across the a " transporter in the pro imal tubule. The secreted h*drogen ions combine with filtered"$%& leading to reabsorption as previousl* described . Aldosterone primarily acts distally to increase #) and 1 secretionresultin in increased acid and potassium e=cretion . The net result is a h*po/alemic metabolic al/alosis. The almost completereabsorption of "$%& in the setting of reduced $M, leads to the parado=ical findin of an acidic urine despite the presence ofe tracellular al/alosis .

Contraction Al;alosis and #ypo;alemia

$ontraction al/alosis occurs whenever there is a loss in bodil* fluid that does not contain "$%& . In this setting, which is most commonl*due to diuretics , the e tracellular volume contracts around a fi ed quantit* of "$%& resulting in a rise in +"$%& -. ote that in this setting,the total bod* bicarbonate is the same as shown in the figure below.

The direct effect of contraction is largel* minimi;ed b* the release of " from cell buffers, thereb* lowering the plasma +"$%& -toward normal. "owever, if $@ reduction b* diuretics result in h*povolemia, then as in vomiting, the release of angiotensin andaldosterone will be stimulated. This then leads to an increase in "$%& absorption and increased " and secretion. The increasein potassium secretion result in the development of hypo;alemia which also pla*s a ver* important role in maintaining theal/alosis.

#ypo;alemia"*po/alemia is ver* commonl* associated with metabolic al/alosis. This is due to # factors: 1) the common causes of metabolical/alosis !vomiting, diuretics, mineralocorticoid e cess) directl* induce both " and loss !via aldosterone) and thus also cause

h*po/alemia and #) h*po/alemia is a ver* important cause of metabolic al/alosis. "*po/alemia causes metabolic al/alosis b*three mechanisms. The initial effect is b* causing a transcellular shift in which leaves and " enters the cells, thereb* raising thee tracellular p". The second effect is b* causing a transcellular shift in the cells of the pro imal tubules resulting in an intracellularacidosis, which promotes ammonium production and e cretion. Thirdl*, in the presence of h*po/alemia, h*drogen secretion inthe pro imal and distal tubules increases. This leads to further reabsorption of "$%& . The net effect is an increase in the net acide cretion.

!osthypercapnia

The normal stimulus to respirator* acidosis is a compensator* increase in "$%& reabsorption b* the /idne* and thus an increasein plasma +"$%& -. Treatment with mechanical ventilation in this disorder leads to a rapid reduction in the p$%#. The plasma"$%& will however remain elevated, resulting in the development of metabolic al/alosis. The maintenance of al/alosis in thissetting is unclear. "owever chronic respirator* acidosis is thought to be associated with $l loss in the urine leading to h*povolemiaand h*pochloremia. 2estoration of $l and volume balance tends to correct the disorder.

@ineralocorticoid e=cess

23
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24/41

The common causes of metabolic al/alosis cause and maintain metabolic al/alosis due to hypo9olemia induced secondaryhyperaldosteronism which leads to increased acid e cretion and h*po/alemia. $onditions of mineralocorticoid e cess such as$onnEs s*ndrome, e cess steroid administration and $ushingEs s*ndrome produce a state of h*peraldosteronism which also leadsto metabolic al;alosis and hypo;alemia' In these conditions, the e tracellular volume is e panded and the patient ma* haveh*pertension. In these patients, metabolic al/alosis is perpetuated b* the effects of hypo;alemia !not h*povolemia) which leads toincreased ammonium production, h*drogen secretion and bicarbonate reabsorbtion

Dia nosis of @etabolic Al;alosis

%nce it has been determined that a patient has metabolic al/alosis, the etiolog* is usuall* obvious from the histor*. If there is nopertinent histor*, then one can assume that the al/alosis is due to one of the three most common causes: 1) vomiting, #) diuretics,&) mineralocorticoid e cess. To differentiate between these conditions, it is usuall* helpful to measure the urinary chlorideconcentration .

In causes of metabolic al/alosis associated with a reduction in the $M, there will be a stimulus for avid a and $l reabsorption toreplenish e tracellular volume. In these setting urinary Cl should be e=pected to be 9ery lo>, less than 07 me$.4 .

Grinar* a is not a reliable measure of e tracellular volume in this setting because if the al/alosis is such that not all of the filtered"$%& can be reabsorbed, then some will be e creted with a and the urinar* a ma* be high. Thus, it ma* appear that thevolume status is euvolemic or h*pervolemic when it is not.

If the urinar* $l is low, indicating a h*povolemic state, then administration of a$l and water to replenish the e tracellular volumeshould stop the stimulus for aldosterone production and in turn should lead to appropriate e cretion of e cess "$%& andimprovement of h*po/alemia. Thus, leading to correction of the metabolic al/alosis. 8uch causes of metabolic al/alosis are said tobe saline responsi9e' 8ee table below.

In contrast, states of mineralocorticoid e=cess are associated >ith an e=panded 9olume and sometimes h*pertension. Theurinary Cl >ill be hi h N 2/ me$.4 ' In these patients, administration of saline would further e pand the e tracellular volume andworsen h*pertension. It would not correct the al/alosis which is primaril* due to h*po/alemia. 8uch causes of metabolic al/alosisare said to be saline resistant .

Urine Cl L 07 me$.4Saline Responsi9e

Urine Cl N 2/ me$.4Saline Unresponsi9e

$auses of saline resistant metabolic al/alosis can further be distinguished based on whether or not the patient is h*pertensive.ineralocorticoid e cess states tend to be associated with h*pertension while e ogenous al/ali load, Barrters and LitelmanEs

s*ndrome are associated with normal blood pressure .

?reatment

8aline 2esponsive metabolic al/alosis

Re e=pand 9olume >ith ormal Saline ! (rimar* Therap*)8upplement with (otassium to treat h*po/alemia !al/alosis associated with se9ere h*po/alemia will be resistant to

volume resuscitation until is repleted)

" bloc/ers or ((Is if vomiting< L suction to prevent further losses in " ions

9iscontinue diuretics

ceta;olamide if 8 contraindicated due to $"@. ! onitor for h*po/alemia)

"$l or "5$l in emergenc*. !"$l can cause hemol*sis, "5$l should not be used in liver disease)

"emodial*sis in patients with mar/ed renal failure

24

!rimary mineralocorticoid e=cess

"=o enous Al;ali load

Barrter s or Gitelman s syndrome

Se9ere #ypo;alemia 1L 0'/

Pomitin or naso astric suction

Diuretics

!osthypercapnia

Cystic Eibrosis

4o> chloride inta;e


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8aline 7 Gnresponsive metabolic al/alosis ! ineraldocorticoid e cess)

8urgical removal of mineralocorticoid producing tumor ldosterone inhibitor

$ inhibitor.

9iscontinue steroids

!otassium repletion !onl* intervention needed to treat the al/alosis)

Respiratory Acidosis

Respiratory acidosis is a clinical disorder characterized by a low arterial pH (< .!"#$ an elevation in the p%&' (hypercapnia# and acompensatory increase in the plasma H%&!)*.

"*percapnia also occurs in metabolic al/alosis, but this is rather a response to the high arterial p", which distinguishes the two.

!athophysiolo y s mentioned previousl* , brea/down of carboh*drates and fats result in the endogenous production of up to #' mol of $%#. This $%#, ifnot e creted via ventilation will combine with "#% to form carbonic acid in the following reaction:CO0 ) #0O W #0CO+ CA W #) ) #CO+

n* increase in ($%# due to increased $%# production is rapidl* handled b* increased alveolar ventilation. Because of the lungRse cellent capacit* to e crete e cess $%#, increases in ($%# are alwa*s due to h*poventilation and never to increased $%# production.

"*poventilation can occur with an* interference in the respirator* process. 8ee table. $ommon etiologies are neuromuscular disorders,$ 8 depression, disorders of the chest wall, chronic obstructive lung disease and acute airwa* obstruction.

@or a discussion on the compensator* mechanisms of respirator* acidosis, clic/ here .

Causes of respiratory acidosis

A C S depression(' Opioids0' O=y en in patient >ith chronic hypercapnia+' Central sleep apnea2' C S lesion7' "=treme obesity !ic;>ic;ian syndrome

B euromuscular disorders(' @yasthenia ra9is0' Guillain Barre+' A4S2' !oliomyelitis7' @uscular dystrophy&' @ultiple Sclerosis

C Chest >all or ?horacic Ca e Abnormality(' 1yphoscoliosis0' Elail Chest+' @y=edema2' Rib Eracture7' Scleroderma

2 Disorders affectin as e=chan e(' CO!D0' Se9ere asthma or pneumonia+' !neumothora= or #emothora=2' Acute pulmonary edema

7 Air>ay obstruction(' Aspiration of forei n body0' Obstructi9e sleep apnea+' 4aryn ospasm

Symptoms8*mptoms are caused b* acute respirator* acidosis and not b* chronic respirator* acidosis and usuall* include neurologic abnormalities.Initial s*mptoms include headache, blurr* vision, restlessness, and an iet*, which can progress to tremors, asteri is, delirium, andsomnolence or coma !$%# narcosis). 8evere h*percapnia increases cerebral blood flow and cerebrospinal fluid pressure. 8igns of

increased intracranial pressure such as papilledema ma* be seen.

The tendenc* to develop neurologic abnormalities in acute respirator* acidosis is due to the rapid reduction in $8@ p". $%# is lipid solubleand rapidl* crosses the blood brain border, leading to a decline in $8@ p". In contrast, "$%& is a polar compound that does not readil*

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cross the blood border and thus is not available to counteract the actions of $%#. Thus acute respirator* acidosis promotes a greater fall in$8@ p" than acute metabolic acidosis, which ma* e plain wh* neurologic abnormalities are seen less often in the latter. In chronicrespirator* acidosis, the $%# accumulates at a much slower rate, allowing renal compensation to return the arterial p" and ultimatel* $8@p" toward normal. Therefore neurologic abnormalities are also seldom seen in chronic respirator* acidosis.

?reatment

Treat underl*ing disorder 8uppl* o *gen

$orticosteroids and bronchodilators to reduce airwa* inflammation and resistance.

echanical ventilator if ventilation fails.

Respiratory Al;alosis

2espirator* l/alosis is an acid base disturbance characteri;ed b* elevated arterial p", h*perventilation resulting in a low p$%# and ausuall* compensator* decrease in plasma "$%& concentration.

!athophysiolo y2espirator* l/alosis results from an elevation in alveolar ventilation that causes a fall in the partial pressure of dissolved carbon dio ide.The fall in ($%# causes a compensator* fall in plasma "$%& concentration as was decribed previousl* .

The causes of 2espirator* l/alosis are shown in the table below. It is ver* commonl* induced b* what the bod* or patient perceives as astressor. The stressor which is often associated with an iet*, pain, and infection stimulates the $ 8 leading to h*perventilation. %thercommon causes are h*po emia, sepsis, liver failure and ( . spirin into ication is an interesting cause of respirator* al/alosis which canalso cause an elvated anion gap acidosis.

A C S stimulation(' pain0' An=iety, !sychosis+' Ee9er 2' CPA7' @enin itis, encephalitis&' ?umor, trauma5' Dru s: Salicylate also causes metabolic acidosis , methyla=anthines, theophylline,aminophyllines'

6' !re nancy, pro esterone

B #ypo=emia or tissue hypo=ia(' #i h altitude0' !ulmonary disease: pneumonia, interstitial fibrosis, !", pulmonary edema+' C#E2' #ypotension7' Se9ere anemia&' Aspiration

C Chest Receptors stimulation(' Elail Chest0' #emothora=+' !"

2 @iscellaneous disorders('Gram ne ati9e septicemia 9ery early clinical si n of septicemia0' #epatic failure+' @echanical hyper9entilation2' #eat e=posure7' Reco9ery from metabolic acidosis

$linical anifestations

$linical manifestations of respirator* al/alosis var* according to duration and severit* and depend on the underl*ing disease process.

In acute respirator* al/alosis, acute onset of h*pocapnia can cause cerebral vasoconstriction. Therefore, an acute decrease in ($%#reduces cerebral blood flow and can cause neurologic s*mptoms, including di;;iness, mental confusion, s*ncope, sei;ures, paresthesias,numbness around the mouth. This acute drop in ($%#, result in a substantial drop in $8@ p" not seen in chronic respirator* al/alosis ormetabolic al/alosis. In metabolic al/alosis, the change in $8@ p" occurs much slower due to the relative inabilit* of "$%& to cross theblood brain barrier in comparison to $%#.

In addition some complaints ma* be unrelated to the change in p". @or e ample, patients with ps*chogenic h*perventilation often complainof chest tightness, headache, d*spnea, and other somatic s*mptoms that ma* be related to an iet* and not al/alemia. cute respirator* al/alosis also causes intracellular shift of potassium and phosphates potentiall* resulting in h*po/alemia and

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h*pophosphatemia. The h*po/alemia is usuall* mild. "*pocalcemia t*picall* results, due to an increase in albumin bound calcium and ma*lead to tetan* and a positive $hvoste/ or Trousseau sign.

Treatment

Treat the underl*ing cause: o *gen, diuretics, etc. @or an ious patient, reassurance, rebreathing into paper bag !raises the inspired ($%#).

Teach breath holding techniques during episodes.

If intubated, reduce minute ventilation b* ad0usting rate, tidal volume.

Gsuall* self limited since muscles wea/ness will suppress ventilation.

If the (a$%# is corrected rapidl* in patients with chronic respirator* al/alosis, metabolic acidosis ma* develop due to the previouscompensator* drop in serum bicarbonate.

@i=ed Acid Base Disorders

i ed acid base disorders occur when there is more than one primar* acid base disturbance present simultaneousl*. The* arefrequentl* seen in hospitali;ed patients, particularl* in the criticall* ill.

hen to suspect a mi=ed acid base disorder:

1. The e pected compensator* response does not occur #. $ompensator* response occurs, but level of compensation is inadequate or too e treme

&. Dhenever the ($%# and +"$%& - becomes abnormal in the opposite direction. !i.e. one is elevated while the other isreduced). In simple acid base disorders, the direction of the compensator* response is alwa*s the same as the directionof the initial abnormal change.

5. p" is normal but ($%# or "$%& is abnormal

4. In anion gap metabolic acidosis, if the change in bicarbonate level is not proportional to the change of the anion gap. orespecificall*, if the delta ratio is greater than # or less than 1.

6. In simple acid base disorders, the compensator* response should never return the p" to normal. If that happens, suspecta mi ed disorder.

i ed metabolic disorders

1. Anion Gap and ormal Anion Gap Acidosis .This mi ed acid base disorder is identified in patients with a delta ratio less than ( which signifies that the reduction inbicarbonate is greater than it should be, relative to the change in the anion gap. Thus, implicating that there must beanother process present requiring buffering b* "$%& , i.e a concurrent normal anion gap acidosis.

ample: >actic acidosis superimposed on severe diarrhea. !note: the delta ratio is not particularl* helpful here since the

diarrhea will be clinicall* obvious)

(rogressive 2enal @ailure

9 during treatment

T*pe IM 2T and 9

#. Anion Gap Acidosis and @etabolic Al;alosisThis mi ed acid base disorder is identified in patients with a delta ratio reater than (, which signifies a reduction inbicarbonate less than it should be, relative to the change in the anion gap. This suggests the presence of anotherprocess functioning to increase the bicarbonate level without affecting the anion gap, i.e. metabolic al/alosis.

amples:

>actic acidosis, uremia, or 9 in a patient who is activel* vomiting or who requires nasogastric suction.

(atient with lactic acidosis or 9 given sodium bicarbonate therap*.

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&. ormal Anion Gap Acidosis and @etabolic Al;alosisThis diagnosis can be quite difficult, because the low "$%& and low ($%# both move bac/ toward normal whenmetabolic al/alosis develops. lso, unli/e elevated anion gap acidosis, the anion gap will not indicate the presence of theacidosis.

ample:

In patients who are vomiting and with diarrhea !note: all acid base parameters ma* fall within the normal range)

i ed respirator* and respirator*7metabolic disorders

"aving a good /nowledge of compensator* mechanisms and e tent of compensation will aid in identif*ing these disorders.2emember= compensation for simple acid base disturbances alwa*s drives the compensating parameter ! ie , the ($%#, or+"$%& -) in the same direction as the primar* abnormal parameter ! ie , the +"$%& - or ($%#). hene9er the !CO0 and *#CO+-are abnormal in opposite directions, ie , one abo9e normal >hile the other is reduced, a mi=ed respiratory and metabolicacid base disorder e=ists'

Rule of thumb:

Dhen the ($%# is elevated and the +"$%& - reduced, respirator* acidosis and metabolic acidosis coe ist. Dhen the ($%# is reduced and the +"$%& - elevated, respirator* al/alosis and metabolic al/alosis coe ist

The above e amples both produce ver* e treme acidemia or al/alemia and are relativel* eas* to diagnose. "owever more often,the disorder is quite subtle. @or e ample, in cases of metabolic acidosis, the "$%& is low and ($%# low. If the ($%# is normal ornot aqequatel* reduced, this ma* indicate a subtle coe isting respirator* acidosis.

i ed acid base disorders usuall* produce arterial blood gas results that could potentiall* be e plained b* other mi ed disorders.%ftentimes, the clinical picture will help to distinguish. It is important to distinguish mi ed acid base disorders because wor/ up andmanagement will depend on accurate diagnosis.

1. Chronic Respiratory Acidosis >ith superimposed Acute Respiratory Acidosisample:

cute e acerbation of $%(9 secondar* to acute pneumonia

$%(9 patient with worsening h*poventilation secondar* to o *gen therap* or sedative administration

#. Chronic Respiratory Acidosis and Anion Gap @etabolic Acidosisample:

$%(9 patient who develops shoc/ and lactic acidosis

&. Chronic Respiratory Acidosis and @etabolic Al;alosisample:

(ulmonar* insufficienc* and diuretic therap*

or $%(9 patient treated with steroids or ventilation !important to recogni;e as al/alemia will reduce acidemicstimulus to breathe)

5. Respiratory Al;alosis and @etabolic Acidosisample:

8alic*late into ication

Lram negative sepsis

cute cardiopulmonar* arrest

8evere pulmonar* edema

(lease note that it is impossible to have more than one respirator* disorder in the same mi ed disorder!i.e. concurrent respirator*

al/alosis and respirator* acidosis)

!ractice Cases28


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These case studies are pro&ided to gi&e you practice dealing with some of the topics that were discussed in the acid base tutorial% ach casecontains a clinical presentation followed by e&aluati&e studies% Answers are pro&ided after each case but it would probably be best if youformulate your own answer to each .uestion before reading below for the answer .

Case (

55 *ear old moderatel* deh*drated man was admitted with a two da* histor* of acute severe diarrhea. lectrol*te results: a1&5, #.A, $l 1'C, "$%& 16, BG &1, $r 1.4.

BL: p" 3.&1 p$%# && mm"g"$%& 16 p%# A& mm"g

Dhat is the acid base disorder

nswer !using the step by step approach )

1. #istory : Based on the clinical scenario, li/el* acid base disorders in this patient are:

ormal anion gap acidosis from diarrhea or levated anion gap acidosis secondar* to lactic acidosis as a result of h*povolemia and poor perfusion.

0' >oo/ at the p# .The p" is low, !less than 3.&4) therefore b* definition, patient is acidemic .

+. Dhat is the process >oo/ at the !CO0, #CO+ .($%# and "$%& are abnormal in the same direction , therefore less li/el* a mi ed acid base disorder. eed to distinguish theinitial change from the compensator* response. low ($%# represents al/alosis and is not consistent with the p". low "$%&represents acidosis and is consistent with the p", therefore it must be the initial change. The low ($%# must be the compensator*response. 8ince the primar* change involves "$%& , this is a metabolic process, i.e. etabolic cidosis.

2. $alculate the anion apThe anion gap is a !$l "$%& ) ? 1&5 !1'C 16) ? 1'8ince gap is less than 16, it is therefore normal.

7. Is compensation ade$uate $alculate the estimated ($%#.Gsing DinterEs formula= ($%# ? 1.4 +"$%& -) C F # ? 1.4 16 C F # ? &' &5.

8ince the actual ($%# falls within the estimated range, we can deduce that the compensation is adequate and there is no seperaterespirator* disorder present.

Assessment : ormal anion gap acidosis with adequate compensation most li/el* secondar* to severe diarrhea .

Case 0

## *ear old female with t*pe I 9 , presents to the emergenc* department with a 1 da* histor* of nausea, vomiting, pol*uria, pol*d*psiaand vague abdominal pain. (. . noted for deep sighing breathing, orthostatic h*potension, and dr* mucous membranes.

>abs: a 1 , 6.', $l A&, "$%& 11 glucose 3#', BG &C, $r #.6.G : p" 4, 8L 1.'1', /etones negative, glucose positive . (lasma /etones trace.

BL: p" 3.#3 "$%& 1' ($%# #&


nswer !using the step by step approach )


levated anion gap acidosis secondar* to 9 , or levated anion gap acidosis secondar* to lactic acidosis in the setting of vomiting and pol*uria which ma* lead to

h*povolemia, and


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+. Dhat is the process >oo/ at the !CO0, #CO+ .($%# and "$%& are abnormal in the same direction , therefore less li/el* a mi ed acid base disorder but not *et ruled out.

gain, need to distinguish the initial change from the compensator* response. low "$%& represents acidosis and is consistentwith the p", therefore it must be the initial change. To maintain the ($%#oo/ at the p# .The p" is low, !less than 3.&4) therefore b* definition, patient is acidemic .


gain, need to distinguish the initial change from the compensator* response. low "$%& represents acidosis and is consistentwith the p", therefore it must be the initial change. The low ($%# must be the compensator* response. 8ince the primar* changeinvolves "$%& , this is a metabolic process, i.e. etabolic cidosis.

2. $alculate the anion ap

The anion gap is a !$l "$%& ) ? 1&5 !33 A) ? 5C8ince gap is greater than 16, it is therefore abnormal.

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7. Is compensation ade$uate $alculate the estimated ($%#.Gsing DinterEs formula= ($%# ? 1.4 +"$%& -) C F # ? 1.4 A C F # ? 1A.4 #&.4.

8ince the actual ($%# falls within the estimated range, we can deduce that the compensation is adequate and there is no seperaterespirator* disorder present.

&. 8ince anion gap elevated, calculate the delta ratio to rule out concurrent metabolic al/alosis.

Delta ratio ? K nion gap ? ! L 1#) pppppp ? !5C 1#) pp ? &6 ? #.6

Deppppppppp K +"$%& -p a !#5 +"$%& -)ppppp !#5 A) pp 15

8ince the delta ratio is greater than #, we can deduce that there is a concurrent metabolic al;alosis . This is li/el* due tovomiting.

nother possibilit* is a pre e istent high "$%& level due to compensated respirator* acidosis. But we have no reason to suspectrespirator* acidosis based on the histor*.

Assessment : i ed elevated anion gap metabolic acidosis and metabolic al/alosis li/el* due to lactic acidosis and vomiting .

Case 2

3' *ear old man with histor* of $"@ presents with increased shortness of breath and leg swelling.

BL: p" 3.#5, ($%# 6' mm"g, (%# 4# "$%& #3


nswer !using the step b* step approach )


cute respirator* acidosis secondar* to acute pulmonar* edema



eed to distinguish the initial change from the compensator* response. "$%& is on the high side of normal and is not consistentwith the p". ($%# is high and represents acidosis and is consistent with the p". Therefore it must be the initial change. The highnormal "$%& must be the compensator* response. 8ince the primar* change involves ($%#, this is a respirator* process, i.e.2espirator* cidosis.

2. Is respirator* process acute or chronic, estimate e pected e=tent of compensation . If acute, e pected compensation is O+ #CO+ - ? 1 m q for ever* 1' mm "g H($%# .$hange in ($%# ? 6' 5' ?#'.Therefore elevation in +"$%& - ? #'


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a 1&C, 5.#, $l 1'C, "$%& 15

Because of her histor*, the ph*sician decides to chec/ her urine electrol*tes.

Grine chemistr*: &1, a 1'', $l 1'4

Dhat is the acid base disorder Dhat is the li/el* cause

nswer

(' #istory : ote that in this scenario, we are not given an arterial blood gas. Therefore we must deduce the diagnosis primaril*from the histor* and the limited wor/up available.

The patients presents to an outpatient visit ver* as*mptomatic. Besides the histor* of diarrhea, there is nothing else in the histor* tosuggest an active acid base disorder. "owever, her serum electrol*tes indicate a low "$%& concentration which suggestsacidosis.De can safel* rule out a chronic respirator* al/alosis as basis of the low "$%& since h*perventilation would be evidenton e am. In the absence of other data, we have to assume that the patient has a metabolic acidosis.

De are not given serum electrol*tes and therefore we cannot calculate the anion gap, but based on the histor*, we can assumethat the patient does not have lactic acidosis, /etoacidosis, uremia and has not ingested an* to ins.

ssuming the patient has normal anion gap acidosis, our differential becomes diarrhea vs 2T . De have to consider 2T in thispatient, because of the histor* of 80ogrenEs.

0. Urine Anion Gap . De are given urine electrol*tes and thus to distinguish between 2T and diarrhea, we can calculate the urineanion gap , otherwise /nown as the Grinar* et $harge. 2emember that the G L is an indirect measure of ammonium e cretion,which should be ver* high in the presence of acidosis if renal function is not impaired.

G L ? a $lG L ? 1'' &1 1'4 ? #6.

positive G L suggest 2T because in the setting of diarrhea, ammonium chloride concentration in the urine would be high andthe G L would be negative. postive value suggests that the /idne* is unable to adequatel* e crete ammonium, leading to areduction in net acid e cretion and thus metabolic acidosis.

Assessment : etabolic acidosis li/el* secondar* to renal tubular acidosis.

ote that further wor/up is needed in order to distinguish the different t*pes of 2T . 80ogrenEs is most commonl* seen in t*pe I 2Tand is associated with h*po/alemia and a urine p" that that does not fall be*ond 4.&, even in the setting of increased acid load.$hec/ing the urine p" after administration of " 5$l would establish the diagnosis.

Case 6

3# *ear old man with histor* of $%(9 presents to the hospital with alcoholic /etoacidosis.

8erum chemistr*: a 1&6, 4.1, $l C4, "$%& #4, BG #C, $r 1.5, BL: p" 3.#', ($%# 6', "$%& #4, (%# 34Grine /etones #

If the patientRs previous anion gap was 1#, what was his bicarbonate concentration prior to the onset of /etoacidosis

Answer

The patient is acidemic, with a high ($%# and a "$%& that is slightl* elevated. This would seem to suggest an acute respirator*acidosis. "owever we are told that the patient has developed alcoholic /etoacidosis which should produce an elevated anion gapmetabolic acidosis. In that case we would e pect the bicarbonate level to be ver* low, but it is not. This would suggest that thepatient either has a concurrent metabolic al/alosis or that the bicarbonate level was ver* high prior to the onset of metabolicacidosis.

The patient is not vomiting or ta/ing diuretics and there is no reason to supect a metabolic al/alosis. De are told of the histor* of$%(9, which is commonl* associated with chronic respirator* acidosis. In these patients, bicarbonate levels are ver* high due torenal compensation. Therefore we suspect that the patient had a high bicarbonate level prior to the onset of . The metabolicacidosis from caused a drop in his bicarbonate level, down to a normal level.

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The anion gap is a !$l "$%& ) ? 1&6 !C4 #4) ? #6, this confirms our suspicion of an elevated anion gap metabolic acidosis.

In patients with /etoacidosis, we suspect a 1:1 change in the elevation of the anion gap vs the reduction of the bicarbonate level.That is, the elevation in the anion gap will be matched b* an equal reduction in bicarbonate. 8ee delta ratio .

If the previous anion gap was 1#, then change in L ? #6 1# ?15.The change in bicarbonate should also be 15, therefore the previous bicarbonate level should be 15 #4 ? &A.

Case 5

4' *ear old insulin dependent diabetic woman was brought to the 9 b* ambulance. 8he was semi comatose and had been ill for several da*s. $urrent medication was digo in and a thia;ide diuretic for $"@.>ab results8erum chemistr*: a 1, #.3, $l 3A, "$%& 1A Llu C14,>actate '.A urine /etones &

BL: p" 3.51 ($%# "$%& 1A p%# C#


nswer !using the step b* step approach )

1. #istory : Based on the clinical scenario, possible acid base disorders in this patient are:

levated anion gap acidosis secondar* to 9 etabolic al/alosis in the setting of thia;ide diuretics use.

0' >oo/ at the p# .ote that the p" is normal which would suggest no acid base disorder.

introduction to acid base disorders

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