PHYSIOLOGY
Acidebase physiology: new
concepts
Tom Hickish
Andrew D Farmery
Abstract
The traditional approach to acidebase physiology is based on the Hender-
soneHasselbalch equation which is derived from the CO2 =HCO3
buffer
system. However, it is becoming increasingly recognized that this is an
incomplete analysis as it focuses on only one of the six reactions involving
Hþ and can lead to the incorrect assumption that CO2 and HCO3
are inde-
pendently adjusted factors that ultimately determine pH. In 1983, Stewart,
a Canadian physiologist, proposed that a fuller understanding of acid
ebase physiology required consideration of biological fluids as a complex
dynamic system, taking into account the interactions of all the chemical
species involved. He showed that the true independent variables control-
ling the pH of any given fluid compartment are: the difference in the concen-
tration of ‘strong ions’, the total concentration of ‘weak acid’, and the PCO2.
Importantly, Hþ and HCO3
are dependent variables and it is incorrect to
think of them as being specifically regulated to manipulate pH. This review
will discuss the importance of pH homeostasis and highlight the implica-
tions of the Stewart approach in our understanding of acidebase control
mechanisms and disorders. In particular, the true mechanisms by which
the kidney regulates plasma pH will be discussed, emphasizing key miscon-
ceptions that have been propagated as a result of the traditional approach.
Keywords Acidebase physiology; acidosis; Stewart approach
Royal College of Anaesthetists CPD Matrix: A101.
Importance of HD
Maintenance of plasma pH (
log10 [Hþ]) within the range 7.35e
7.45, which corresponds to an intracellular pH of neutrality (where
[Hþ] ¼ [OH
]; wpH 6.8 at 37 C), is an essential requirement for
life. But why should an ion that is only present in nanomolar con-
centrations be so critical? The answer is twofold: firstly, metabolic
intermediates are completely ionized at neutral pH and therefore
are maximally trapped within the cell; secondly, the activity of all
proteins (including enzymes) is exquisitely sensitive to changes in
Hþ concentration as their binding characteristics are determined by
their net charge. Therefore the Hþ concentration is tightly regulated
to provide conditions for optimal intracellular function.
Problem
The main problem faced by the homeostatic control mechanisms
is the defence against a massive daily acid load. The acid
Tom Hickish BA BM BCh is Foundation Doctor at East Sussex Health Trust,
UK. Conflicts of interest: none declared.
Andrew D Farmery BSc BCh MA MD FRCA is Fellow and Tutor in Medicine
and Physiology at Wadham College, Oxford, UK. Conflicts of interest:
none declared.
ANAESTHESIA AND INTENSIVE CARE MEDICINE 16:11
produced by the body can be thought of as either volatile or non-
volatile:
Volatile acid is mainly carbonic acid (H2CO3) which is produced
by the hydration of CO2:
CO2 þ H2 O#H2 CO3 #Hþ þ HCO3

Therefore, although CO2 is not itself an acid as it does not contain
a hydrogen ion to donate, it can instead be thought of as repre-
senting a potential to create an equivalent amount of carbonic
acid. At rest (with a CO2 production of 200 ml/minute) the daily
load of CO2 is at least 15,000 mmol/day.
Non-volatile acids contribute much less to daily acid production
with a net production of 1e1.5 mmol/kg/day or 70e100 mmol of
Hþ per day in an adult. These acids are produced by the
incomplete metabolism of carbohydrates (e.g. lactate), fats (e.g.
acetoacetate, b-hydroxybutyrate) and proteins (e.g. sulphate,
phosphate). Note that these are actually bases rather than acids.
However this terminology is common place because they have
been formed by the liberation of an Hþ from their parent acid.
It is clear that these amounts are several orders of magnitude
greater than the normal body Hþ concentration and thus robust
defence mechanisms are essential for conditions compatible with
life.
Defence mechanisms
The traditional approach to acidebase balance is that there are
two component defence mechanisms:
 physicochemical buffering
 acid excretion from the lungs (as CO2) and the kidneys.
In order to understand these mechanisms it is first necessary
to understand the principles of buffer systems within the body.
Physicochemical buffering
A buffer is a solution that resists changes in pH when an acid or
base is added to it. A buffer consists of an undissociated weak
acid (HA) and its conjugate base (A
) and can be represented by:
HA#Hþ þ A

A buffer typically consists of a solution which contains a weak
acid HA mixed with the salt of that acid (e.g. NaA). The principle
is that the salt provides a reservoir of A
to replenish [A
] when
A
is removed by reaction with Hþ. The body has a huge
buffering capacity and as this process happens instantaneously,
physicochemical buffering provides a powerful first defence
against acidebase perturbations.
The main buffer systems in the different fluid compartments
of the body are as follows:
 blood
 haemoglobin: HHb # Hþ þ Hb

 bicarbonate: H2CO3 # Hþ þ HCO3

 interstitial fluid
 bicarbonate: H2CO3 # Hþ þ HCO3

 intracellular fluid
 proteins: HPr # Hþ þ Pr

 phosphate: H2 PO4
# Hþ þ HPO4 2

578 Ó 2015 Elsevier Ltd. All rights reserved.
 PHYSIOLOGY
The main buffer system in the extracellular fluid is bicar-
bonate/carbonic acid:
CO2 þ H2 O#H2 CO3 #Hþ þ HCO3

Since the concentration of carbonic acid is very low compared to
the other components, the acid moiety of the system is CO2 and
so the above equation can be simplified to:
CO2 þ H2 O#Hþ þ HCO3

Indeed, it is from this equation that the HendersoneHasselbalch
equation is derived:

 
pH ¼ pK þ log HCO3
ðaPCO2 Þ
 
so; pH is a function of HCO3
PCO2
The HendersoneHasselbalch equation forms the basis of the
traditional approach to acidebase balance: it is used to show
that, for the CO2 =HCO3
buffer system to be sustainable, the
body must ultimately regulate ½HCO3
 and PCO2.
It has therefore been taught that the longer-term control of
acidebase homeostasis is achieved by respiratory control of
plasma PCO2 through changes in alveolar ventilation (occurs
over minutes), and by the control of HCO3
excretion by the
kidneys (occurs over hours to days). Importantly, the traditional
approach views these two variables as independently adjusted
factors that ultimately determine pH.
Alternative approach: the Stewart method
However, in 1983, the Canadian physiologist Peter Stewart pro-
posed an alternative approach to acidebase regulation. He pro-
posed that a full understanding of acidebase physiology requires
consideration of biological fluids as a complex dynamic system:
one needs to consider all the chemical species involved and how
they interact chemically with each other.
He made the argument that the traditional approach only fo-
cuses on one of six reactions that involves Hþ ions, and ignores
the other five:
 water: H2O # Hþ þ OH

 ‘weak’ acids in water (mainly protein and inorganic
phosphate): HA # Hþ þ A

 carbonate: CO32
þ Hþ # HCO3

 bicarbonate: HCO3
þ Hþ # CO2
 electrical neutrality equation: [SID] þ [Hþ] ¼ ½HCO3
 þ
[A
] þ ½CO3 2
 þ [OH
]
 conservation of mass for ‘A’: [ATOT] ¼ [HA] þ [A
]
Stewart employed the fundamental principles of physical
chemistry to derive the factors that must determine [Hþ]. He
applied the principles of electroneutrality, conservation of mass,
and the law of mass action (the requirement that all equilibriums
must be simultaneously satisfied) to the various components
which constitute body fluids:
 water
 weak ions e weak ions are produced from substrates
which only partially dissociate when dissolved in water.
These can be classified into two groups:
ANAESTHESIA AND INTENSIVE CARE MEDICINE 16:11
 carbon dioxide and associated ions (volatile)
 weak acids (non-volatile) which are mainly protein and
inorganic phosphate
 strong ions e strong ions are ions which are fully disso-
ciated in biological solutions (e.g. Naþ, Kþ, Cl
, lactate).
That is their dissociation equilibria have a pK far removed
from the local pH.
Stewart created a model of human solutions by adding each of
these constituents in turn and solving simultaneous equations
based on the dissociation equilibria of all the reactions involving
Hþ. In his analysis he emphasized that the concentrations of the
various chemical species present are the variables of the system,
which can be of two types:
Dependent variables have values that are determined internally
by the system. They are determined by the equations (chemical
equilibria) which determine the system and can be altered only
by changes on the values of the independent variables.
Independent variables have values that are determined by
processes or conditions which are external to the system; they
are imposed on the system rather than being determined by it.
From his analysis, Stewart showed that that [Hþ] in a physi-
ological solution is in fact a function of three independent
variables:
 The strong ion difference (SID) / the total concentration
of fully dissociated cations in solution minus the total
concentration of fully dissociated anions in solution ¼
{[Naþ] þ [Kþ] þ [Ca2þ] þ [Mg2þ]}
{[Cl
] þ [lactate
]}
z [Naþ] þ [Kþ]
[Cl
] / controlled by the kidney. For
the mathematical reader, proof of the dependency of [Hþ]
on SID is shown in the Appendix.
 Total concentration of weak acid ([ATOT]) / predomi-
nately phosphate and proteins such as albumin (controlled
by the liver) and Hb (controlled by the haemotopoetic
system).
 PCO2 / controlled by the lung.
Therefore, in a given body fluid compartment, any changes in
pH must be because of a change in one of more of these inde-
pendent variables. Crucially, it is misleading of the traditional
approach to think of HCO3
as being specifically regulated
to manipulate pH as HCO3
cannot be individually or
primarily altered. Stewart concluded that ½HCO3
 is a marker for
acidebase disturbances rather than a causative factor.
The Stewart approach and the traditional approach both agree
on the role of the lungs in regulating acidebase balance through
CO2 excretion and manipulation of arterial PCO2. However, it is
the role of the kidney that is disputed. Using the Stewart
approach, we can discover the true mechanisms by which the
kidney regulates plasma pH, and can appreciate key mis-
conceptions that have been propagated as a result of the tradi-
tional approach.
Role of the kidneys in regulation of plasma pH
Conventionally, the kidney is viewed as regulating plasma pH by
regenerating HCO3
with the net effect of excreting Hþ. How-
ever, Stewart shows that moving Hþ ions between compartments
does not actually change pH because it does not alter any of the
579 Ó 2015 Elsevier Ltd. All rights reserved.
 PHYSIOLOGY
independent variables present. [Hþ] will be maintained by a
change in the dissociation of water to reverse any [Hþ] fluctua-
tions: the water dissociation equilibrium is able to provide an
essentially inexhaustible source or sink for Hþ ions. Therefore,
the Stewart approach proposes that the true mechanism by
which the kidney regulates plasma pH is by changing the flux of
strong ions across the renal tubules: the kidney alters the SID. A
key question is which strong ion? [Naþ] is tightly controlled to
maintain osmolarity and control plasma volume, and [Kþ] needs
to be tightly controlled to ensure appropriate cardiac and
neuromuscular function. Therefore, the kidney alters [Cl
] to
regulate acidebase balance.
In order to understand this process more fully, we shall
discuss the commonly taught mechanisms of renal acidebase
handling, but will reconcile misconceptions derived from the
traditional approach with a more accurate perspective based on
the Stewart approach.
The kidney plays two important roles:
 reabsorption of filtered HCO3

 excretion of Cl
and increase in the SID (traditional
approach focuses on concomitant regeneration of buffered
HCO3
).
Reabsorption of the filtered HCO3L
Approximately 4e5 mol/day is filtered through the glomerulus
and all of this is reabsorbed. This process takes place mainly in
the proximal tubule and is mediated mainly by Naþ-driven sys-
tems (secondary active transport). The mechanisms for this
process are shown in Figure 1.
Intracellular Hþ, formed from the reaction between H2O and
CO2, is secreted into the tubular lumen mainly by passive Nþ/Hþ
exchange using a protein carrier. Secreted Hþ ions combine with
HCO3
in the tubular lumen to form H2CO3 which dissociates to
H+ secretion and HCO3– reabsorption in the tubular cells
–HCO
Blood
NBCl
Cl–
Na+
ATP
K+
Interstitium
From Bruno CM, Valenti M. Acid-base disorders in patients with chronic obstructive pulmonary disease:
a pathophysiological review. J Biomed Biotechnol 2012; 2012: 1–8.
ATP, adenosine triphosphate; NHE3, sodium/hydrogen exchanger.
Figure 1
ANAESTHESIA AND INTENSIVE CARE MEDICINE 16:11
CO2 and H2O. Carbonic anhydrase in the luminal cell membrane
ensures that this dissociation occurs rapidly. The CO2 passively
diffuses into the cell where it is hydrated and converted back to Hþ
and HCO3
by intracellular carbonic anhydrase. The reabsorbed
HCO3
passively exits the cell across the basolateral cell mem-
brane in exchange for Cl
. Therefore, secondary active Hþ secre-
tion into the lumen keeps luminal [Hþ] high and intracellular [Hþ]
low. This drives the reaction in the lumen to produce CO2 and H2O,
and the reaction in the cell to produces HCO3
and Hþ. The Hþ
ions thus undergo a futile cycle to reabsorb the filtered HCO3
.
However, under normal conditions, the kidney already re-
absorbs the entire filtered load of bicarbonate. Therefore, this
process can only protect against a metabolic alkalosis, but it
cannot correct for a metabolic acidosis: the kidney cannot reab-
sorb more bicarbonate than is filtered. Therefore, the kidney
must employ other mechanisms.
Regeneration of HCO3L and excretion of HD?
The traditional approach teaches that the kidney is also able to
regenerate the bicarbonate that has been depleted during the
buffering of non-volatile acids, with the subsequent excretion of
an equivalent amount of Hþ in the urine.
The theory for this process is shown in Figure 2 and takes
place in the intercalated cells of the distal tubule and collecting
duct. Intracellular Hþ is formed through the same process as
described in the proximal tubule and the Hþ is actively trans-
ported into the distal tubular lumen via an Hþ-ATPase pump. In
order for there to be a net excretion of Hþ, unlike in the proximal
tubule, the secreted Hþ must not react with tubular HCO3
as
otherwise the CO2 formed within the tubular lumen would be
returned to the cell, effectively recycling the secreted Hþ.
Unbuffered Hþ cannot account for much acid loss because the
minimum urinary pH is only about 4.5: we would need to pass
Filtration
ATP H+
Na+
+ NHE3 H+ + –HCO3
3
H+
H2CO3
H2CO3
Carbonic
anhydrase
H 2O
+
CO2 CO2 + H2O
Tubular fluid
580 Ó 2015 Elsevier Ltd. All rights reserved.

Titration of non-volatile acids. H+ secreted into the tubular fluid combines
with phosphate and a new HCO3 – is generated within the cell
Na+
ATP
K+
–HCO
3
AE
Blood
Cl–
H2CO3
CO2
Interstitium
From Bruno CM, Valenti M. Acid-base disorders in patients with chronic obstructive pulmonary disease:
a pathophysiological review. J Biomed Biotechnol 2012; 2012: 1–8.
ATP, adenosine triphosphate.
Figure 2
thousands of litres of pH 4.5 urine to excrete the daily non-
volatile acid load. The alternative is for the secreted Hþ to bind
to urinary buffers of which phosphate is the most important as it
is present at significant concentrations. At the prevailing pH
values in most biological systems, monohydrogen phosphate
ðHPO4 2
Þ and dihydrogen phosphate ðH2 PO4
Þ are the two
species present:
Hþ þ HPO4 2
#H2 PO4

The pKa of this reaction is 6.8. Under normal conditions the pH
of the glomerular ultrafiltrate is 7.4 (that of plasma), meaning
that phosphate will initially be predominantly in the mono-
hydrogen form and so can combine with more Hþ in the renal
tubules. However, the capacity of the phosphate buffer system is
limited under acidotic conditions for two reasons. Firstly, the
amount of phosphate present in the distal tubule cannot be
varied significantly. Secondly, as the urinary pH falls to less than
5.5 the phosphate buffer system becomes fully saturated.
Therefore, although this ‘titratable acidity’ is an important part of
excretion of non-volatile acids under normal circumstances, it
cannot be an important mechanism in acidebase regulation
when the ability to increase renal Hþ excretion is required.
It is a common misconception that ammonia (NH3) provides
this extra urinary buffer capacity: it is thought that lipid soluble
NH3 is produced in the tubular cell and diffuses into the tubular
fluid where it is effectively trapped by buffering secreted Hþ and
being converted to water-soluble ammonium (NH4þ). However,
this has to be incorrect: the pKa for ammonia is so high (w9.2)
ANAESTHESIA AND INTENSIVE CARE MEDICINE 16:11
PHYSIOLOGY
Filtration
HPO42–
Na+
ATP +HPO42–
+ H+ K+/H +
H+
ATP
H2PO4–
H 2O NaH2PO4
+
CO2
Tubular fluid
that at both extracellular and intracellular pH, it is present almost
entirely in the acid form NH4þ, which is not a useful buffer.
The real answer is that, under acidotic conditions, it is
ammonium (NH4þ) excretion itself that fulfils this regulatory role
as, unlike phosphate, its excretion can increase markedly as
urine pH falls. As shall now be discussed, in order to understand
the physiology of this mechanism, it is vital to adopt the Stewart
approach.
Ammonium excretion
Ammonium is produced predominantly within the proximal tu-
bule cells from glutamine by the action of the enzyme gluta-
minase. The expression of glutaminase is controlled by the
prevailing pH as the mRNA involved in its transcription is more
stable under acidotic conditions. Glutamine enters the cell from
both the peritubular capillaries (80%) and the filtrate (20%).
The majority of the ammonium is involved in a process
known as ‘medullary cycling’ which maintains an increasing
interstitial concentration of ammonium from cortex to medulla
and low concentrations of ammonium in the distal tubule fluid
(in a way analogous to the familiar cortex to medulla sodium
chloride osmolality gradient, and using a similar kind of coun-
tercurrent multiplication). A model of ammonium handling and
excretion by the kidney is shown in Figure 3. The ammonium
produced in the proximal tubule cells is secreted into the tubular
lumen by replacing Hþ on the Naþ/Hþ exchanger. This proxi-
mally produced ammonium is reabsorbed from the tubular fluid
in the medulla as it passes along the thick ascending limb of the
loop of Henle by replacing Kþ on the triple transporter (Naþ/Kþ/
581 Ó 2015 Elsevier Ltd. All rights reserved.
 PHYSIOLOGY

Schematic representation of ammonium handling and excretion by the kidney

Glutamine Expression is
Glutaminase
HCO3– pH sensitive

Increasing
NH4+
interstitial
ammonium
Na+ NH4+
Lumen

Interstitium 2Cl–
Na+
NH4+ NH4+ NH4+
2Cl–
Na+
NH4+

RhCG
NH4+

NH4+
Expression is
NH4+ pH sensitive
medullary
NH4+ accumulation NH +
4

Figure 3

2Cl
). This means that the amount of ammonium entering the thus allowing the body to retain the strong ions Naþ and Kþ. It is
distal tubule is small. Some of the interstitial ammonium returns this excretion of Cl
without an equivalent amount of strong ion
to the late proximal tubule and enters the medulla again (i.e. that is the true cause of the correction of plasma pH as it results
recycling occurs). The net effect is that there is a large ammo- in an increase in the SID.
nium concentration gradient between the medullary interstitium
and the luminal fluid of the medullary collecting duct. Classification of acid-base disturbances using the Stewart
This provides a mechanism by which the amount of ammo- approach
nium excretion can be highly regulated simply by altering the
As discussed, the Stewart approach shows that disturbances in
permeability of the collecting duct to ammonium (analogous to
plasma pH can occur only via changes in the independent vari-
how anti-diuretic hormone regulates water homeostasis by
ables: pCO2, the SID, and [ATOT].
altering the collecting duct water permeability). The molecular
Therefore, as with the traditional approach, respiratory aci-
mechanisms for this process are only just being elucidated, but it
doses or alkaloses are those in which the primary disturbance is
seems that specific membrane proteins from the family of Rhesus
the PCO2. However, for metabolic acidoses and alkaloses,
glycoproteins play an important role in regulating the transport
whereas the traditional approach focuses on primary distur-
of ammonium down its concentration gradient into the collecting
bances in HCO3
, the Stewart approach shows that the true
duct. Importantly, this mechanism is pH sensitive: it has been
primary disturbance must in fact be in the SID or [ATOT]. Primary
shown that the expression of the Rhesus C glycoprotein (RhCG)
respiratory disturbances are compensated by metabolic re-
in the collecting duct increases in the presence of a prolonged
sponses, and primary metabolic disturbances are compensated
metabolic acidosis, thus leading to an increase in ammonium
by respiratory responses.
excretion.
But how does ammonium excretion correct a metabolic
Respiratory acidosis is a process caused by a rise in arterial PCO2
acidosis? Certainly, excretion of NH4þ per se does not excrete any
which is proportional to VCO2/VA (where VCO2 is the amount of
protons in the traditional sense (as discussed above). However
CO2 produced by the body and VA is alveolar ventilation).
NH4þ is a weak anion that when excreted is accompanied by Cl
,

ANAESTHESIA AND INTENSIVE CARE MEDICINE 16:11 582 Ó 2015 Elsevier Ltd. All rights reserved.
 PHYSIOLOGY

Therefore respiratory acidosis occurs during alveolar hypo- HCO3
cannot affect plasma Hþ or HCO3
concentrations unless
ventilation (e.g. asphyxia, neuromuscular disease, chronic pul- changes in the independent variables also occur. Although the
monary disease, opiate toxicity) or increased CO2 production by traditional approach remains the most widely used in everyday
the body (e.g. during exercise, malignant hyperthermia). clinical practice, it fails to understand the true mechanisms of
acidebase disorders and pH homeostasis. A
Respiratory alkalosis is a process caused by a fall in arterial
PCO2 and is always due to alveolar hyperventilation (e.g.
excessive minute ventilation if mechanically ventilated, physio- Appendix
logical response to hypoxia, anxiety attacks, salicylate
intoxication). The dependency of [Hþ] on SID is not necessarily intuitive.
However, this can be proven from consideration of just two of
Metabolic acidosis is a process caused by either a decrease in the the conditions listed in the bullet point list on page 579; namely
SID, or by an increase in [ATOT]. A decrease in the SID may be the dissociation equilibrium of water, and the preservation of
caused by either the generation of organic strong anions (e.g. electroneutrality.
lactate following a hypoxic insult, or ketone bodies in diabetic Consider the dissociation of water:
ketoacidosis), by the loss of strong cations (as with the loss of Kþ
and Naþ in severe diarrhoea), by the mishandling of strong ions H2 O#Hþ þ OH

(as with renal tubular acidosis), or by the addition of exogenous
strong anions (as with iatrogenic acidosis or poisoning). The iat- At equilibrium, the Law of Mass Action dictates that ½Hþ  ½OH

rogenic metabolic acidosis that results from the infusion of saline ¼ Kw ½H2 O where Kw is the dissociation constant for water.
provides an elegant example of how changes in the SID disturb Given that the concentration of water is effectively constant,
acidebase balance. Saline does not contain any significant quan- this can be re-written as:
tity of Hþ ions and therefore by the traditional approach it would
not be expected to alter pH. Whilst it is true that the pH of saline   K0 w
OH
¼ þ where K0 w is another constant: Equation A1
solution may be 6, which in physiological terms is too acidic to ½H 
sustain life, the Hþ load it presents is trivial. If Hþ were the only
consideration, we would need to administer 1000 litres of saline to Now consider the conditions required for electroneutrality of a
increase a patient’s ‘base deficit’ by just 1 mmol/litre. solution of sodium chloride in water:
However, saline is a ‘SID zero’ solution and thus causes the ½Naþ  þ ½Hþ  ¼ ½Cl-  þ ½OH- , which re-arranges to:
extracellular fluid SID to decrease: saline causes [Cl
] to increase  þ  
proportionally more than [Naþ] as Cl
is normally present at a Na
½Cl-  ¼ ½OH- 
Hþ
lower concentration (extracellular [Cl
] ¼ 110 mM; extracellular
[Naþ] ¼ 140 mM). This causes a relative hyperchloraemia and a Given that the difference in the strong (fully dissociated) cations
decrease in the SID, with a subsequent acidosis. In contrast, and anions is SID, we have:
Hartmann’s solution has a SID much closer to the SID of extra-  
cellular fluid and thus does not have as profound an effect on SID ¼ ½OH-  - Hþ Equation A2
plasma pH.
Now recall equation A1, and substitute the [OH
] term in
Metabolic alkalosis is a process caused by either an increase in equation A2 with K0 w/[Hþ] from equation A1 to get:
the SID, or a decrease in [ATOT]. An increase in the SID may be
K0 w  þ 
caused by the loss of more strong anions than strong cations (as SID ¼ - H
with diuretic therapy, or from the loss of Cl
following vomiting ½Hþ 
of gastric secretions in pyloric stenosis or nasogastric aspiration)
or by the administration of more strong cations than strong an- Now multiplying both sides by [Hþ] gives:
ions (as with infusion of NaHCO3 or large volumes of blood  þ 2  
containing sodium citrate). A decrease in [ATOT] can result from H þ SID, Hþ - K0 w ¼ 0 Equation A3
causes of hypoalbuminaemia such as the nephrotic syndrome or
liver failure. Equation A3 is seen to be a quadratic equation which can be
solved for [Hþ] in terms of SID and K0 w, hence SID is an inde-
Conclusion pendent determinant of [Hþ].

In the words of Stewart, the conventional understanding of acid

ebase balance is ‘cluttered with jargon, chemically meaningless
derived equations, a misunderstanding of what is really
happening, and an artificial use of the HendersoneHasselbalch
equation as the only equation determining acidebase balance in
any body fluid’. This review has emphasized how the Hþ and
HCO3
concentrations are dependent variables whose values are
determined by the SID, [ATOT], and pCO2: movement of Hþ or
FURTHER READING
http://www.anaesthesiamcq.com/AcidBaseBook/ABindex.php.
Kellum JA, Elbers PWG. Stewart’s textbook of acidebase, 2nd edn. 2009.
Lulu Enterprises Ltd, UK.
Sirker AA, Rhodes A, Grounds RM, Bennett ED. Acidebase physiology:
the traditional and the modern approaches. Anaesthesia 2002; 57:
348e56.

ANAESTHESIA AND INTENSIVE CARE MEDICINE 16:11 583 Ó 2015 Elsevier Ltd. All rights reserved.