lecture of stewart 1&2

8/7/2019 LECTURE OF STEWART 1&2

1/81

ACID-BASE BALANCE;

EFFECT OF FLUID AND NUTRITION

A Stewart Approach

Yohanes WH George


2/81

This approach is morefundamentally correctthan the conventional and it provides insightinto biologicalmechanisms.

Anyone who studies acid-base physiology shouldbecome familiar with thisapproach.

HOW TO UNDERSTAND

ACID-BASE

A quantitative Acid-Base Primer

For Biology and Medicine

Peter A. Stewart

Edward Arnold, London 1981

Peter A.Stewart.


3/81

TRADITIONAL APPROACH

Hendersen-Hasselbalch (H-H)

pH = pK x Log [HCO3

-/(0.03 x pCO2)]

RELATIONS


4/81

QUANTITATIVE METHOD OF STEWART

CAUSAL -

MECHANISM


5/81

The impact of Stewart analysis has been slow in

coming but there has been a recent resurgencein interest, particularly as this approachprovides explanations for several areas whichare otherwise difficult to understand

Dilutional acidosis

Acid-base disorders related to changesin plasma albumin concentration


6/81

TERM AND CONCEPTS

Solutions as a system :

.it is a general property of system thatthe quantitative results ofseveralinteracting but independent mechanismscannot be explained or understood solely interms of the action of any single one of

these mechanisms.

(Stewart 1983, p144-5)


7/81

GENERAL PRICIPLES

Electrical neutrality:

All the solutions are electrically neutral, thatis, the total concentration of cations equalsthe total concentration of anions

Conservation of mass:

The amounts of the major components (water,electrolytes, metabolites, etc) remainconstant unless these are added or removedfrom outside or created or destroyed bychemical reaction


8/81

Biochemistry of Aqueous

Solutions

All solutions in human biology contain

water and aqueous solution. Provide avirtually inexhaustible source of [H+]

[H+] is determined by the dissociation of

water(Kw) into H+ and OH- ions.


9/81

Changes in H+ occur not as a result of howmuch H+ is added or removed, but as a

consequence ofwater dissociation.

H2O H+ + OH-


10/81

Stewart: A formula for the calculation of theequilibrium value of a [H+]

is

complex

easy and quick using computer

BUT


11/81

Two types of variables

DETERMINANTS OF [H+] INBIOLOGICAL SOLUTION

Dependentvariables

Independentvariables


12/81

Dependent variableshave values which are determined internallyby thesystem. They are determined by the equationswhich determine the system and can be altered onlyby changes in the values of the independentvariables.

Independent variables

have values which are determined by processes or

conditions which are externalto the system; theyare imposed on the system rather than beingdetermined by it.


13/81

Strong IonsDifference

pCO2

ProteinConcentration

PHYSICOCHEMICALRx

CONSERVATION ofMASS

ELECTRONEUTRALITY

H+

HCO3-

OH-

tCO2A-

CO3=

INDEPENDENT VARIABLESDEPENDENT VARIABLES


14/81

ISF,RBC &PLASMA

DETERMINANTS OF BLOODpH

Liver


15/81

Why is this concept of dependentand independent variables so

important?

The reason is that the values of all dependent

variables are determined by and can be calculated

from the values of independent variables.

In body fluids, [H+] is a dependent variables,

therefore can be calculated if the values of the

independent variables are known.


16/81

BASIC IDEA


17/81

PHYSIOLOGY..

Two substances A and B reversibly combining toform substance C, and when the reaction is atequilibrium the equation governing theequilibrium is:

[A] x [B] = K x [C]

K is the rate constant for reaction


18/81

Neutral, acidic and basic solutions aredefined with refference to the value ofsquare root of Kw

Neutral : [H+] = sq rt Kw = [OH-] Acidic : [H+] > sq rt Kw > [OH-]

Basic : [H+] < sq rt Kw < [OH-]


19/81

Acid:any substance which, when added to anaqueous sol, will cause increase in [H+]

Base:

any substance which, when added to anaqueous sol, will cause decrease in [H+]


20/81

Strong ions/electrolyte:substance that exist as essentially

completely dissociated in aqueoussolution,

KA> 104 Eq/L

- Na+, Cl-, K+, Ca+2, SO4-2 (Inorganik)

- Lactate (Organik),


21/81

2 3 4 5 6 7 8 9

100

80

70

60

50

40

30

20

10

%

Ioniz

ed

pH

pK

CO

2HCO

3-

Albumin

L

actate

CHEMICAL EQUILIBRIUM

Whether an ion is strong or weak depends on its pK (i.e., the pH at which half of

the substance is ionized, the other half not). The pK of Lactate is 3.9 (i.e, more than

99% of it is ionized at pH greater than 6). Carbonic acid and albumin are weak acids

because substantial portions of them are neutral in the physiologic range, requiring

that their ionized concentrations be computed.


22/81

Weak ions/electrolyte:

substance that are only partiallydissociated in aqueous solution,

KA between 104 and 10-12 Eq/L

Carbon dioxide (volatile) bicarb

system

Weak acids Albumin & Pi (non-

volatile)


23/81

0%

20%

40%

60%

80%

100%

cations anions

gamblegram for plasm

HCO3-

Alb-

Ca++

Mg+

UA-

H+

lactate-

K+

Cl-

Na+

Strong and weakions


24/81

DETERMINED [H+] IN A SPECIFIC SITUATIONS


25/81

1. PURE WATER

Characteristic of water;

Strongly ionic substances dissociate when placed

in water Water it self dissociates, but only a little

Water containts a lot of water

Molecular weight are small (18) but

Molar concentration is >> (55.3 mol/l at 370C)


26/81

Water dissociates as follow;

H2O H+ + OH-

Very rapid reaction, equilibrium is reached instantaneously in

biological solution

At equilibrium

[H+].[OH-] = Kw.[H2O]

Kw is very small, 4.3 x 10-16

Eq/l at 370

C and temperaturedependent, e.g at 250C is 1.8 x 10-16Eq/l


27/81

A new constant

Kw = Kw x [H2O]

Kw is product of the two constant;

- Kw and

- The molar concentration of water

Lets find the pH of pure water


28/81

[H+] x [OH-] = Kw

If we know the Kw, we still need to find one of the othervariables, [OH-]

Electroneutrality;

[H+] [OH-] = 0

[H+] = [OH-]

[H+] = Kwif [H+] = Kw (neutral)if [H+] > Kw (acidic)if [H+] < Kw (basic)


29/81

2. STRONG ELECTROLYTES IN PUREWATER

Water dissociation;

[H+] x [OH-] = Kw equation 0

Electroneutrality;

[H+] - [OH-] + [Na+] - [Cl-] = 0 equation #1

Substitute Kw/[H+] for [OH-]

[H+] Kw/[H+] + [Na+] [Cl-] = 0

[H+]2 + [H+]([Na+] [Cl-]) Kw = 0

Quadratic equation a.x2 + b.x + c = 0

[H+] = - ([Na+] [Cl-])/2 + {([Na+] [Cl-])2/4 + Kw}

SID = STRONG IONS DIFFERENCE


30/81

And solving for[H+]

[H+] = Kw + SID2/4 SID/2 equation #2[OH-] = Kw + SID2/4 + SID/2 equation #3

In these solution it is clear that if the hydrogen ionconcentration changes

the SID must have changed


31/81

If SID is positive and bigger than 106 Eq/l

we can see that Kw becomes insignificant,and equation #3 becomes very nearly thesame as:

[OH-] = [SID]

We can use this equation and equation #0to derive the hydrogen ion concentration:

[H+] = Kw/[SID]


32/81

If the SID is negative and biggerthan about 106 Eq/liter then equation#2 simplifies out to:

[H+] = - [SID]

But such solutions are not commonlyencountered in biological systems


33/81

SKETCH; RELATIONSHIP BETWEEN SID,H+AND OH-

SID

() (+)

[H+] [OH+]

In biological solutions at 370C, the SID nearlyalways positive, usually around 40 mEq/Liter


34/81

A more complex setup Adding a weakelectrolyte

A weak electrolyte, [Atot ]: One that partially dissociated in the pH range

The most important in plasma is albumin

Represents the total amount of weak

electrolytes produced by biochemical reactionswithin the body, or represents the totalamount of available buffer in body.

3. ADDING A WEAKELECTROLYTE


35/81

Weak Acids:

HA (such as albumin) dissociates to form H+and A-, as follow:

HA H+ + A-

Combined with two equation and the term of

electroneutrality[H+] x [OH-] = Kw eq#0

[H+] + [OH-] + [SID] + [A-] = 0 eq#1A

Dissociation of acids and conservation of

mass;[H+] x [A-] = KA x [HA] eq #4

[HA] + [A-] = [ATot ] eq #5


36/81

Identify the independent variables (Kw,[SID],[ATot ]

and KA) and dependent one ([H+],[OH-],[HA] and [A-]

Eliminate all dependent variables apart from [H+]from the equation by substitution:

[OH-] = Kw/[H+] from eq #0

[HA] = [ATot ] [A-] from eq #5

And substituting eq#5 into eq#4

[A-] = Ka x [ATot ] /([H+] + KA)


37/81

Substitute these values into equation #1A, and get;

[SID]+[H+]-Kw/[H+]KA[ATot ]/(KA+[H+]) =0 eq #6

Use a computer programe to find the [H+]

ITS EASY AND QUICK !!!


38/81

Take a mixture of strong ions and water, andexpose it to CO

2

What happen to CO2gas when exposed to water

Dissolved

React with water to form carbonic acid

Bicarbonate or Carbonate ions

4. STRONG IONS WITH CO2


39/81

a. CO2 can dissolved:

CO2 (gas) CO2 (dissolved)

Equilibrium:

[CO2 dissolved

] = SCO2 x PCO2 equation #7A

SCO2 = Solubility of CO2, 3.0 x 105 Eq/l/mmHg at 370C


40/81

b. Can react with water;

CO2+ H

2O H

2CO

3

Equilibrium;

[CO2 dissolved

] x [H2O] = K x [H

2CO

3]equation #7B

If [H2O] constant;

[H2CO

3] = K

Hx PCO

2

KHat 370C is 9 x 108 Eq/l


41/81

c. H2CO

3dissociate;

H2CO

3H+ + HCO

3-

Equilibrium;

[H+] x [HCO3

-] = K x [H2CO

3]

[H+] x [HCO3-] = KC x PCO

2equation #8

KCis 2.6 x 1011 Eq/l2/mmHg


42/81

d. HCO3- rapidly dissociate:

HCO3-H+ + CO

32

Equilibrium;

[H+] x [CO3

2] = K3 x [HCO3

-] equation #9

K3is 6 x 1011 Eq/l

K3is 6 x 10 11 Eq/l


43/81

THE SIX SIMULTANEOUS EQUATIONS USED BY STEWART

Water Dissociation Equlibrium

[H+] x [OH-] = Kw

Electrical Neutrality Equation

[SID] + [H+] = [HCO3

-] + [A-] + [CO3 2 ] + [OH-]

Weak acid Dissociation Equilibrium

[H+] x [A-] = KA x [HA]Conservation of Mass for A

[ATot

] = [HA] + [A-]

Bicarbonate Ion Formation Equilibrium

[H+

] x [HCO3] = Kc x pCO2

Carbonat Ion Formation Equilibrium

[H+] x [CO3

2 ] = K3 x [HCO3

-]


44/81

A 4th polynomial order

ax4 + bx3+ cx2 + dx + e = 0Substitute;

a.[H+]4 + b.[H+]3 + c.[H+]2 + d.[H+] + e = 0Where,

a = 1

b = [SID] + KA

c = { KA([SID] [A

Tot]) K

w K

c.pCO

2}

d = - {KA(Kw + K

c.pCO

2) K

3.K

c.CO

2}

e = - (KA.K

3.K

c.pCO

2)


45/81

[SID]+[H+

]-KC.pCO2/[H+

]-KA.[ATot ]/(KA+[H+

])-K3.KC.pCO2/[H+]2

-Kw/[H+

]=0

[H+] dan [HCO3

-] = ([SID], pCO2, [A

Tot])

In these solution it is clear that if the hydrogen or

bicarbonate ion concentration changes

the SID,ATot and pCO2 must have changed


46/81

The practical significance of all thismaths

If we want to calculate the pH, we must:1. Know the concentrations of the

strong ions, and

2. Plug these value into equations;

Note:

If you add basic or acidic substance, you cannot just

say We added so much hydroxide so the pH will

change by so much.

You have to work things out using the equations.


47/81

BLOOD PLASMA

Na+

K+

Mg++

Ca++

Cl-

XA-Posfat-

Alb-

HCO3-

OH- CO32-

SID

H+

ATot

Unmeasured Anion

CATION ANION


48/81

USING STEWART FOR

CLINICAL GAIN


49/81

Clasification (Fencl et al)

ACIDOSIS ALKALOSIS

I. Respiratory PCO2 PCO2

II. Nonrespiratory (metabolic)

1. Abnormal SID

a. Water excess/deficit SID, [Na+] SID, [Na+]

b. Imbalance of strong anions

i. Chloride excess/deficit SID, [Cl-] SID, [Cl-]

ii. Unidentified anion excess SID, [XA-]

2. Non-volatile acids

i. Serum albumin [Alb] [Alb]

ii. Inorganic phosphate [Pi] [Pi]


50/81

RESPIRATORYSIMILAR WITH H-H

PCO2 Ph

PCO2 Ph


51/81

METABOLIC

SID

WEAK ACID


52/81

S I D

CHANGING THE WATER CONTENT OF PLASMA

(CONTRACTION ALKALOSIS AND DILUTIONAL

ACIDOSIS

CHANGING THE Cl- (HYPERCHLOREMIC

ACIDOSIS AND HYPOCHLOREMIC ALKALOSIS)

INCREASING THE CONCENTRATION OF

UNIDENTIFIED ANIONS (ORGANIC ACIDOSIS)


53/81

Na+ = 140 mEq/L

Cl- = 110 mEq/L

SID = 30 mEq/L

OH- = 30 mEq/L

Na+ = 70 mEq/L

Cl- = 55 mEq/L

SID = 15 mEq/L

OH- = 15 mEq/L

1 liter2 liter

DILUTIONAL ACIDOSIS

NaCl + H2O Na+ + Cl- + H+ + OH- + H2O

H2O


54/81

Na+ = 140 mEq/L

Cl- = 110 mEq/L

SID = 30 mEq/L

OH- = 30 mEq/L

Na+ = 154 mEq/L

Cl- = 154 mEq/L

SID = 0 mEq/L

OH- = 0 mEq/L1 liter

2 liter

PLASMA PLUS NORMAL SALINE


55/81

Na+ = (140+154)/2 mEq/L= 147 mEq/L

Cl- = (110+ 154)/2 mEq/L= 132 mEq/L

SID = 15 mEq/L

OH- = 15 mEq/L

2 liter

HYPERCHLOREMIC ACIDOSIS RESULTING FROM

NORMAL SALINE

=


56/81

Na+ = 140 mEq/L

Cl- = 110 mEq/L

SID = 30 mEq/L

OH- = 30 mEq/L

Cation+ = 137 mEq/LCl- = 109 mEq/L

Lactate = 28 mEq/L

SID = 0 mEq/L

OH- = 0 mEq/L1 liter

2 liter

PLASMA PLUS RINGERS LACTATE SOLUTION


57/81

Na+ = (140+137)/2 mEq/L= 139 mEq/L

Cl- = (110+ 109)/2 mEq/L= 110 mEq/L

SID = 29 mEq/L

OH- = 29 mEq/L

2 liter=

NORMAL ACID-BASE STATE FOLLOWING

RINGERS LACTATE


58/81

Na+ = 140 mEq/L

Cl- = 110 mEq/L

SID = 30 mEq/L

OH- = 30 mEq/L

Na+ = 280 mEq/L

Cl- = 220 mEq/L

SID = 60 mEq/L

OH- = 60 mEq/L

1 liter liter

CONTRACTION ALKALOSIS


59/81

Na+ = 140 mEq/L

Cl- = 95 mEq/L

SID = 45 mEq/L

OH- = 45 mEq/L

2 liter

HYPOCHLOREMIC ALKALOSIS


60/81

Na+ = 140 mEq/L

Cl- = 120 mEq/L

SID = 20 mEq/L

OH- = 20 mEq/L

2 liter

HYPERCHLOREMIC ACIDOSIS


61/81

CLINICAL STUDIES


62/81

Hyperchloremic Acidosis

Kellum JA, Bellomo R, Kramer DJ, Pinsky MR: Etiology

of Metabolic Acidosis During Saline Resuscitation

in Endotoxemia.Shock1998, 9: 364--368.Experimental evidence of the effect of saline

resuscitation on acid-base parameters in an endotoxic

animal model.


63/81

Scheingraber S, Rehm M, Sehmisch C, Finsterer U:

Rapid saline infusion produces hyperchloremicacidosis in patients undergoing gynecologicsurgery.Anesthesiology1999, 90:1265--1270.

Waters JH, Miller LR, Clack S, Kim JV. Cause of

metabolic acidosis in prolonged surgery. Crit CareMed. 1999; 27:2142-6.

A clinical study detailing the acidosis associated withsaline vs. no change in pH with lactated Ringers

solution in patient undergoing major abdominal/pelvicsurgery.


64/81

Liskaser FJ, Bellomo R, Hayhoe M, et al: Role of PumpPrime in the Etiology and Pathogenesis of

Cardiopulmonary Bypass-associated Acidosis.Anesthesiology 2000; 93:1170-1173

Rehm M, Orth V, Scheingraber S, et al: Acid-Base

Changes Caused by 5% Albumin versus 6%Hydroxyethyl Starch Solution in Patients UndergoingAcute Normovolemic Hemodilution: A RandomizedProspective Study. Anesthesiology 2000; 93:1174-1183

Waters JH, Bernstein CA: Dilutional Acidosis following

Hetastarch or Albumin in Healthy Volunteers.Anesthesiology 2000; 93:1184-1187


65/81

These three studies published in the November, 2000 issue of the

journal Anesthesiology provide conclusive evidence that the Chloride

content of volume expanding solutions determines the degree of

acidosis.

In the study by Lisaker, two types of pump-priming solutions for

cardiopulmonary bypass are compared. A hyperchloremic solution and

a solution with acetate and gluconate as metabolizable anions are

used. As predicted, both cause an acute acidosis but with theacetate/gluconate solution, it resolves quickly while the

hyperchloremic solution causes a persistent hyperchloremic

acidosis.

The next two studies found that normovolumic hemodilution with HESor Albumin in saline (Rhem et al.) produced similar amounts of acidosis

while Albumin in a normo-chloremic solution (Waters et al.)

produced no acidosis at all.


66/81

Weak Acids (ATOT

)Jabor A. Kazda A: Modeling of acid-base

equilibria. Acta Anaesth Scand1995, 39: Suppl

107:119--122.

Classification of acid-base disorders remains

controversial. These authors argue for the use of

three types of disorders based on the three

independent variables identified by Stewart.

However, there is little evidence that this approach toclassification is logical or helpful.


67/81

Figge J, Jabor A, Kazda A, Fencl V: Anion gap and

hypoalbuminemia.Crit Care Med. 1998, 26:1807--10.

These authors demonstrate how the anion gap must

be corrected for changes in albumin concentration.Patients with severe disorders of phosphate will

require additional correction not detailed by the

authors but available in this review.


68/81

Wilkes P: Hypoproteinemia, strong ion difference,

and acid-base status in critically ill patients.J Appl

Physiol1998, 84:1740--1748.This excellent observational study details the changes

in strong ion difference as a function of changes in ATOT.The study provides convincing evidence that the

normal physiologic response to hypoalbuminemia is to

reduce the strong ion difference, principally by

increasing the plasma chloride concentration.


69/81

Fencl V and Rossing TH.

Acid-base disorders in Critical Care Medicine

In critically ill patients, nonrespiratory (metabolic)

alkalosis is the most common acid-base disturbance:

it is caused by hypochloraemia and/ or by

hypoproteinaemia.

Information on the concentration of plasma proteins

should be included when evaluating acid-base

status. Their in vitro experiments on effect of plasma

protein concentration on base excess or anion gapsummarised.


70/81

Fencl V and Leith DE

Stewarts quantitative acid-base chemistry

Includes [Ca++] and [Mg++] as strong cations in the SID

formulae. Gives formulae for estimation of anionic

equivalence of albumin (Prx-) and inorganic

phosphates (Piy-) from their measured concentrationsand the pH of the sample.

SID apparent = Na + K + Ca + Mg - Cl

SID effective approx= Bicarbonate + Prx- + Piy-

Unidentified anions [XA-] = SIDapp SIDeff


71/81

Fencl V, Jobor A, Kazda A and Figge J.

Diagnosis of metabolic acid base disturbances incritically-ill patients.

Compares anion gap and base excess approaches

with Fencl & Leiths quantitative formulae. The thirdapproach allows one to detect and quantify even

the most complex acid-base disturbances seen in

critically-ill patients. All the calculations can be done

at the bedside with a simple hand-held calculator.


72/81

Gilfix BM, Bique M and Magder S.

A physical chemical approach to the analysis of

acid base balance in the clinical setting. A different approach, examines the

contributions to net base excess status of Free water

0.3 x (Na-140) Chloride effect

102-(Cl x 140/Na)

Albumin effect

(0.148 x pH-0.818)(42-[alb]) Other species (gap between net base excess and

sum of three above)


73/81

Balasubramanian N, Havens PL and Hoffman GM.Unmeasured anions identified by the Fencl-Stewart method predict

mortality better than base excess, anion gap and lactate in patients in

the pediatric intensive care unit

Confusing because the formulae are essentially thoseof Gilfix et alrather than those of Fencl and Leith.

- Base excess due to free water effect- Base excess due to chloride

- Base Excess due to albumin

= (simplified to) 0.34 x (45-alb)

- Base Excess due to unmeasured anions

= BE - (BEfw + BECl + BEalb)

St DA B ll R H d H lb h


74/81

Story DA, Bellomo R. Hendersen-Hasselbach vs

Stewart: Another Acid-Base Controversy; Review

Article, Crit Care & Shock (2002)2:59-63

Stewart and Base-excess

BE from the Blood Gas Machine

SID effect, mEq/l = A + B

A. Free Water effect on Na+

= 0.3 x ([Na+] 140) B. Corrected Cl- effect

= 102 ([Cl-] x 140/[Na+]) Total weak acids effect, mEq/l

= 0.123 x pH - 0.6310 x (42 - [Albumin])

UA effect = BE ef SID ef ATot ef

C d


75/81

Case study

pH 7.39 BE effects (mEq/l):

CO2 (mmHg) 36 SBE -3.1

Sodium (mEq/l) 139 Free Water ef -0.3

Chloride (mEq/l) 105 Corrected Cl- ef -3.8

Anion Gap (mEq/l) 17.0 Albumin ef 8.8

Albumin (g/l) 18 Unmeasured Anion ef -7.9

1. H-H : Metabolic acidosis but normal anion gap No important UA

2. Stewart: Profound alkalinizing effect of low plasma albumin a

substantial effect of UA

This patient had an elevated Plasma Phosphate 5 mEq/lInadequacy of the H-H approach

SHOW


76/81

INTERACTION BETWEEN

MEMBRANE

f


77/81

Body fluids

RBC

Plasma Interstitial Intracellular

other

PROTEIN


78/81

ISF=13.5L

LIVERSynthesis

Cl-pCO

2

ATot

Lymph

Blood

pH

Na+ Cl-

Alb

CO2

CO2

ICF

dCO

2

Na+

Cl-


79/81

DISTURBANCE

SID

PCO2

Plasma

Protein

[H+][HCO3-]

Etc.

Renal Failure

Lactic acidosis

Keto-acidosisVomiting

Diare

Heart Failure

Lung disease

Hyperventilation

Hypoventilation

Nephrotic Syndrome

Dehydration

Malnutrition

Charge Balance

Dissociation of:

Water

Protein

Carbonic acid


80/81

THANK YOU


81/81

lecture of stewart 1&2

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