Understanding Acid-Base Disturbances Gaps, Deficits and ...msic.org.my/filedownloader.asp?filename=asmic2015_RameshVenkata... · Increased Acid – Acidemia ... Stewart’s definition

Critical Care Medicine

Apollo Hospitals

Chennai

Ramesh Venkataraman, AB(Int Med), AB (CCM)

Consultant, Critical Care Medicine

Department of Critical Care Medicine, Apollo Hospitals

Apollo Hospitals

Understanding Acid-Base Disturbances – Gaps, Deficits and Differences


Understanding Acid-base

Three approaches

Conceptual evolution

Limitations

Comparison

Understanding acid-base

Relative diagnostic efficacy

Prognostic value

Conclusion


Bronsted-Lowry Theory (1923)

Acid - a substance which

donates a hydrogen ion

Volatile vs. Non volatile

(Carbonic vs. Noncarbonic)

Base – a substance which

accepts the H+ from the acid

Acid vs. Base


Acid Homeostasis

Noncarbonic acid

(Metabolic)

Dissolved CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+

Carbonic Acid

(Respiratory)

http://www.google.co.in/url?sa=i&rct=j&q=Lungs&source=images&cd=&cad=rja&docid=A693QEWU2ZLp6M&tbnid=1-ZEfFxULejjJM:&ved=0CAUQjRw&url=http%3A%2F%2Fuabnews.blogspot.com%2F2012%2F02%2Fuab-doc-on-capital-hill-today-breathing.html&ei=71EwUu3oKsPrrQeo7oD4CQ&bvm=bv.51773540,d.bmk&psig=AFQjCNHIz11K4PVwzPKle-Kh4xogQZHaZg&ust=1378984769003817

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Henderson-Hasselbalch equation

pH = 6.10+log([HCO3

-]/0.03xPCO2)

Simplified into the Henderson equation

[H+] = 24 x (PCO2 /[HCO3

-])

Physiologic approach

1. Acid base status determined by net H+ balance

2. Blood pH determined by

PaCO2 – Respiratory component

Bicarbonate – Metabolic component

3. Uses only carbonic acid/bicarbonate buffer system


Primary Disorder And Compensation

Increased Acid – Acidemia

Metabolic – Decreased Bicarbonate

Respiratory – Increased Carbonic acid (PCO2)

Increased Alkali – Alkalemia

Metabolic – Increased Bicarbonate

Respiratory – Decreased Carbonic acid (PCO2)

Dissolved CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+

PCO2 and Bicarbonate go in the same direction in case of

compensation


Metabolic Acidosis

Normal

Na

K

Cations

Cl

HCO3

Anions

Prot

PO4

Na

K

Cations

Cl

HCO3

Anions

Prot

PO4 AG

Na

K

Cations

Cl

HCO3

Anions

Prot

PO4 AG AG

High AG acidosis Normal AG acidosis


Anion Gap - Pitfall

AG – Protein and phosphates

AG MUST be corrected for

albumin and phosphorus

Corrected AG = 2 (S.albumin) + ½ (S.Phosphorus)

AG determines cause of metabolic acidosis

But is underestimated by hypoalbuminemia

Normal

Na

K

Cations

Cl

HCO3

Anions

Prot

PO4

AG


Is bicarbonate a good indicator?

Metabolic derangement

Change in bicarbonate

Change in alveolar ventilation

Altered renal

acidification Altered

HCO3/CO2

equilibrium

Bicarbonate doesn’t accurately reflect

the degree of primary metabolic derangement

Kurtz I et al: Am J Physiol Renal Physiol

294: (2008) F1009 – F1031


(Un)Physiological Approach?

Plasma bicarbonate affected by changes in PaCO2

One component influences other

“Standard” bicarbonate calculation

Sustained changes in PaCO2 modify renal

acidification

Chronic hypercapnia increases plasma bicarbonate

Failure of quantitation of buffers other than

bicarbonate

Isohydric principle

Level of bicarbonate qualitatively reflects status of all buffers

Quantifies magnitude but no insight into cause


Base Excess Approach

Also advocates centrality of H+/ HCO3-

Base excess - metabolic component Assumes 100% oxygenation, 37oC and PCO2 40mmHg

Measure of the contribution of all the ECF buffers

INDEPENDENT of respiratory component

Three relevant acid-base variables

pH

PCO2

Base Excess (BE)


Is SBE a good indicator?

Metabolic derangement

Change in BE

Change in

alveolar ventilation

Altered renal

acidification Altered

HCO3/CO2

equilibrium

BE changes independent of metabolic derangement

in chronic hypo/hypercapnia

Kurtz I et al: Am J Physiol Renal Physiol

294: (2008) F1009 – F1031 Change in SBE


Base Excess has Deficits!!!!!

BE changes with changes in PCO2 invivo

Increased PCO2 causes negative BE

Equilibration occurs across entire extracellular fluid

space (Whole blood + interstitial fluid)

Extracellular or Standard BE

Diluting blood threefold with its own plasma (Hb 5g/dl)

At best a “GUESSTIMATE”

Accurate ONLY when constant hemoglobin “assumed”

Does not help identify the cause


(Mis)understanding acid-base

The serum potassium varies with changes in pH due

to exchange of K+ for H+

Serum K+ concentration is in mmol/L (i.e. 10-3) but that H+

concentration varies in nanomolar range (i.e. 10-9)


(Mis)understanding Acid-base

Vomiting causes metabolic alkalosis by loss of

H+ Why can’t the correction be done with H2O to replenish

the H+?

Saline-induced acidosis - “Dilutional” acidosis Decrease in bicarbonate cannot cause hyperchloremia

How does sodium bicarbonate rectify acidosis?

Fernandez PC, et al. KI 1989; 36: 747-52

Garella S, et al. NEJM 1973; 289: 121-6

Androgue HJ, et al. JCI 1983; 71: 867-83


Stewart’s definition of acid

H+ = OH- - Acid-Base Neutral Acidic solution – H+ > OH-

Basic solution – H+ < OH-

Acids when added to a solution increase H+

Dissociate to yield an anion and H

HA = [H+] [A-]

Complete or partial

Associate with hydroxyl ion

H+ concentration by itself is not a reliable measure of

acidity, alkalinity or neutrality


Determinants of ECF acid-base

[H+] [OH-] = K`w

[H+] [A-] = KA [HA]

[AH] [A-] = [ATOT]

[H+] [HCO3-] = Kc pCO2

[H+] [CO3--] = K3 [HCO3

-]

[SID] + [H+] - [HCO3-] - [A-] - [CO3

--] - [OH-] = 0


H2O

OH-

H+

Determinants of [H+]

Blood Plasma

pCO2

ATOT

SID

Stewart P. Can J Physiol Pharm 1983;61:1444

A- = Ionized weak acid buffer

HA = Non-ionized weak acid buffer

ATOT = Total weak acid buffer

ATOT = 2.43 x total protein g/dl


Strong Ion Difference

These are the “Strong Ions,” so-called because they do not

readily combine with other ions or lose their charge. Conversely,

H+ and HCO3- readily combine, and are called “weak ions”

Na+ Cl- K+

The difference between strong cations and

strong anions is called Strong Ion Difference (SID)

- indicates the net ionic charge of the weak anions; so

it indicates the relative strength of H+ and HCO3-.

Mg++ Ca++ Others (lactate, etc)


Aqueous Solutions

Water

Dissociation

H2O H+ + OH-

Physico - Chemical Approach

H+ and HCO3 – are only DEPENDENT variables

Acids increase water dissociation

1. Determinant of H+ is water dissociation

2. Water dissociation – Determined by SID, ATOT and

PCO2


Physico-chemical Approach

Both H+ and HCO3- are dependent variables

Bicarbonate – just a gap filler between strong cations

and anions

Metabolic component – Strong Ion Difference and ATOT

Respiratory component – PCO2

Six acid-base disorders

SID – increase and decrease – alkalosis and acidosis

ATOT – increase and decrease – acidosis and alkalosis

Respiratory


Stewart Approach

SID = 40


SID vs. AG

Na

K

Cations

Cl

HCO3

Anions

Normal

SIDa Prot

PO4

AG SIDe

AG = (Na+ + K+) – (Cl- + HCO3-)

SIDa (40) = (Na+ + K+) – Cl-

SIDe = Bicarbonate + ATOT-

SIDa = SIDe

SIG = 0


SIG vs. AG acidosis

Na

K

Cations

Cl

HCO3

Anions

High AG or SIG acidosis

SIDa Prot

PO4 AG SIDe

SIG

AG increased

SIDa unchanged

SIDe decreased

SIG increased


SID vs. Normal AG acidosis

Na

K

Cations

Cl

HCO3

Anions

Normal AG or SID acidosis

SIDa Prot

PO4

AG unchanged

SIDa decreased

SIDe decreased equally

SIG = 0

AG SIDe


Strong ion theory - Weaknesses

Very complex to practice

SIG – index of unmeasured anions after discounting for

albumin and phosphates

Advantage negated by correcting AG for albumin and

phosphate

No assessment of compensatory response

Requires routine measurement of multiple other ions

SIG varies with analyzer

Measurement of SIDa

Variable electrolytes being used in definition

SIDe calculated by formula or normograms

Cumbersome at bedside; SIG calculators available


Classification too complex

Normal SIDa Decreased SIDa

Decreased SIDa

But no SIG Decreased SIDe

Increased SIG

Decreased SIDe

No SIG

High ATOT acidosis

Low ATOT alkalosis


More Confusion

Clinical relevance of ATOT acidosis and alkalosis?

No regulation of albumin to maintain acid-base status invivo

Changes in serum albumin do not correlate with changes in

pH or PCO2

Stewart approach – blending of diagnosis and cause

Mathematically accurate but no validation on cause

and effect relationship

Adrogue HJ et al: Kidney Int. 2009; 76: 1239 - 1247


Conceptual Comparison


SIG vs AG

1. AG = [Na+] [K+] – [Cl-] – [HCO3- ]

2. SIDa = Na++K+-Cl-

3. SIDe = HCO3- + A-

4. SIG = SIDa - SIDe [{Na+ + K+ -Cl}- -( HCO3- + A- )]

Combining above 4 equations

SIG = [Na+] [K+] – [Cl-] – [HCO3- ] - [A-]

SIG = AG - [A-]

where [A-]= 2.8 (albumin g/dL)+ 0.6(phosphate mg/dL) at pH 7.4

SIG approximates AGcorr


Diagnostic Accuracy

Dubin A, et al. CCM 2007; 35:1264-1270


Diagnostic and prognostic value

Discordant ABG interpretation - 26 %1

Stewart method superior in identifying patients with high

lactate levels

Can be rectified by incorporating albumin levels in AG

calculations

No difference in quantifying complex acid-base

disorders when AG corrected for albumin 2,3

Conflicting data on prognostic value of SID and SIG1,4,5

1. Balasubramanyan N, et al. CCM 1999; 27(8):1577

2. Moviat M, et al. CCM 2003; 7(3):R41

3. Lautrette A, et al. Minerva Anesthes 2013; 79(10): 1164

4. Cisack RJ et al. ICM 2002; 28(7): 864

5. Kaplan LJ et al. SHOCK 2008; 29(6): 662


Conclusion

Difficult to explain and understand metabolic acid-

base disturbances using bicarbonate-based

approaches

Need to invoke complex mechanisms and hormones

Physico – chemical approach lends itself for easy

explanation and understanding

Blending of diagnosis and cause a concern

More cumbersome

If AG corrected for albumin, no difference between

approaches in diagnostic efficacy

Data conflicting on relative prognostic value of

variables derived from all three approaches


Understanding Acid- base

Final Verdict!!!



Physico - chemical Principles

Electrical Neutrality In macroscopic aqueous solutions, the sum of all positively

charged ions must equal the sum of all negatively charged

ions

Conservation of Mass The amount of a substance remains constant unless it is

added or removed or unless it is generated or destroyed


Na+ K+ Mg++ Ca++

H+

Cl-

alb- CO2

lactate

SO4- -, OH -, others

PO4- -

Electrical Neutrality



[H+] [OH-] = K`w

[H+] [A-] = KA [AH]

[AH] [A-] = [ATOT]

[H+] [HCO3-] = Kc pCO2

[H+] [CO3--] = K3 [HCO3

-]

[SID] + [H+] - [HCO3-] - [A-] - [CO3

--] - [OH-] = 0




[H+]4 + ([SID] + KA)

[H+]3 + (KA ([SID] - [ATOT]) - K`w - Kc pCO2)

[H+]2 - (KA (K`w + Kc pCO2) - K3 Kc pCO2)

[H+] - KA K3 Kc pCO2 = 0



SBE vs SID

The standard base excess

corresponds to the change

in SID required to restore

the plasma (in vivo) to pH

7.40 with pCO2 of 40 mm

Hg

R2=0.9527

-10

-8

-6

-4

-2

0

2

4

6

-8 -6 -4 -2 0 2 4

A/V SIDe

A/V

SB

E

Kellum et al. J Crit Care 1997; 12: 7-12


Saline Acidosis

SID = 40

SID = 32

Serum Na+ 140 mEq/L

Total Body Na+:

140 x 42 = 5880 mEq

Serum Cl- 100 mEq/L

Total Body Cl-:

100 x 42 = 4220 mEq

Add 10L of 0.9% saline

5880 + 1540 = 7420

7420/52 = 142.7 mEq/L

Add 10L of 0.9% saline

4220 + 1540 = 5760

5760/52 = 110.7 mEq/L



How does Saline cause acidosis?

....by decreasing the SID and increasing water

dissociation.



Na+

alb- CO2

lactate


K+ Mg++ Ca++

H+

PO4- -

Cl- Cl-


Saline Acidosis


Cl-

Na+

alb- CO2

lactate

K+ Mg++ Ca++

H+

PO4- -

alb-



Cl- Na+

alb- CO2

lactate


K+ Mg++ Ca++

H+

PO4- -


Further Implications

How does sodium bicarbonate increase the plasma pH?

....by increasing plasma Na+ and thus SID


Sodium Bicarbonate

HCO3- is a dependent variable. It does not

have a Vd. Its concentration is set by the

prevailing pCO2, SID and ATOT.

NaHCO3 increases the plasma pH by

increasing the Na+ and thereby the SID.

This results in decreased water dissociation

and increased pH.


More Acid-Base Questions

Why do patient’s with NG drainage develop alkalemia?

Distinguish H+ loss as HCl from H+ loss as H2O


Geocentric Universe


Copernicus


HCO3-

H+

CO2

Cl-

Buffers

Geocentric Universe


CO2

SID

ATOT

H+

HCO

3-

A-

Post-Copernicus


Changing Practice

Saline causes acidosis, especially in the critically ill

NaHCO3 only works by increasing the serum Na+ (relative

to Cl-)

Lactate is a strong acid but NaL is a salt. Lactate is

acidifying; ATP hydrolysis is not.

Base excess is a reliable measure of metabolic acid-base

status relative to baseline

The anion gap (when the corrected “normal range” is used)

is a reliable measure of missing anions


Base Excess calculations

Calculated the same way, in practice, as SID:

Buffer Base = HCO3- + A-

HCO3 calculated by pH & pCO2 (blood gas machine)

BE = Buffer Base – “expected buffer base”

(expected if pH = 7.4 and pCO2 = 40)

A- calculated using pH & hemoglobin (whole blood)

OR A- calculated using albumin & phos (plasma)


Tight regulation to maintain this level Chemical buffering

Control of PaCO2 - alveolar ventilation

Control of plasma bicarbonate

Renal H+ excretion

Buffers

Uses SOLELY the carbonic acid/bicarbonate buffer system to

assess acid-base status Abundance

Physiological pre-eminence

Both components undergo homeostatic control

Documents

Understanding Acid-Base Disturbances Gaps, Deficits and ...msic.org.my/filedownloader.asp?filename=asmic2015_RameshVenkata... · Increased Acid – Acidemia ... Stewart’s definition