The document discusses acid-base balance and summarizes key concepts from traditional and modern physical-chemical approaches. It explains that the traditional view focused on hydrogen and bicarbonate ion concentrations, while the Stewart model emphasizes three independent variables: partial pressure of carbon dioxide, non-volatile weak acid concentration, and strong ion difference. The Stewart approach provides a more comprehensive understanding of factors influencing pH.

1. Acid base balanceAcid base balance
Suchitra Ranjit MDSuchitra Ranjit MD
Pediatric Intensivist,Pediatric Intensivist,
Apollo Hospitals, ChennaiApollo Hospitals, Chennai

2. For past 100 yrs, acid base has occupied a
special corner of clinical medicine
Physicians generally agree that acid base is
important, but struggle o understand the
science, pathology and application
Also need to be aware of “traditional” vs
modern physical-chemical approach

3. Why knowledge of blood gases are important…
“Long periods of boredom punctuated by moments of
utter panic.”

4. Understanding acid-base physiology:
from Henderson-Hasselbalch to Stewart….
Earliest concepts developed in the beginning of 20th
century
Arrhernius, then Henderson followed by Hasselbalch,
Bronsted Lowry
Acid (HA) is a proton donor, donates H+
Base ( A-) is a proton acceptor, accepts H+

5. •The acidity of the solution is thus a measure of the hydrogen
ion activity
•The normal concentration of H+ is in nanomole range (nmol/L)
• 1 nmol/L = 10 -6
milliequivalents/L
•Serum sodium concentration is 3 million times H+
concentration
•Becoz such figures and units may be confusing, H+
concentration expressed as pH units
•pH = negative log10 of hydrogen ion concentration in nmol/l
•The p refers to the German word ‘potenz’ (power) so pH
means 'power of hydrogen'.
pH = -log10[H+]

6. Relationship between pH and
[H+
]
pH
[H+
]
(nanomoles/l)
6.8 158
6.9 125
7.0 100
7.1 79
7.2 63
7.3 50
7.4 40
7.5 31
7.6 25
7.7 20
7.8 15
A doubling or a halving of
[H+] means a change in
pH by 0.3 either up or
down.

7. Acid production in the body
Volatile acids during oxidative metabolism
• Can leave solution and enter the atmosphere
(e.g. carbonic acid)
•CO2 production: 12,500 mEq of H+ equivalents/day
•Excreted by lungs
Non volatile (fixed) acids produced by daily catabolic load
•Acids that do not leave solution (e.g. sulfuric and
phosphoric acids) until eliminated by the kidney.
Organic acids
Participants in or by-products of aerobic metabolism
(eg, lactic acid)

8. Normal range of pH : 7.35- 7.45
Why maintain pH in such a narrow range ?

9. Plasma pH
• Plasma pH is maintained by homeostasis in the range
7.35 – 7.45
• pH has a widespread effect on cell function
- most cell enzymes work best at physiological pH
• An abnormal pH can result in disturbances in a wide
range of body systems
• Alteration outside these boundaries affects all
body systems but mainly nervous & cardiovascular
(coma, cardiac failure, and circulatory collapse)

10. pH balance regulated by:
1. Chemical buffer system (acts immediately)
1. Respiratory centre in brain stem (1-3
minutes)
2. Renal mechanisms (hours / days)

11. Weak vs strong acids.. Which are
better buffers?
• An acid is “strong” if it dissociates its H+ easily
• ie, corresponding base has low affinity for it
• ie, dissociation constant is high (pK low)
•“Weak” acids only partially dissociate
• Corresponding base has high affinity for it
•Acid and base pairs are present in equimolar proportions
in solution

12. Acid pair can efficiently
buffer (resist) changes in
pH after addition of base
Base pair can efficiently
buffer (resist) changes in
pH after addition of acid
Weak vs strong acids.. Which are better buffers?
•Weak acids: Acid and base pairs are present in equimolar proportions in
solution
•Most effective as buffer when pka of solution closest to physiological pH

13. Physiological buffering systems
Two general categories
1. Bicarbonate/carbonic acid ( HCO3/H2CO3)
buffering system ( ECF and within RBC)
2.Non bicarbonate buffers ( Hb, oxyHb,
organic and inorganic phosphates, plasma
proteins)
Buffers cannot eliminate H+ from the body , but
temper sudden changes in pH and buy time until
problem corrected or a new balance is reached

14. • pH = pKa + log [HCO3
-
]/[H2CO3]
• pH = pKa + log [HCO3
-
]/0.03 x PCO2
• pH = 6.1 + log [HCO3
-
]/0.03 x PCO2
• 7.4 = 6.1 + log 20/1
• 7.4 = 6.1 + 1.3
• The solubility constant of CO2 is 0.03
• The pKa of carbonic acid is 6.1
• Plasma pH equals 7.4 when buffer ratio is 20/1
• Plasma pH may be affected by a change in either the
bicarbonate concentration or the PCO2
• The [HCO -
] and PCO values determine plasma pH
Henderson-Hasselbalch equation
Expresses the relationship of the HCO3/H2CO3
buffering system to pH

15. • pH = pKa + log [HCO3
-
]/[H2CO3]
• pH = pKa + log [HCO3
-
]/0.03 x PCO2
• pH = 6.1 + log [HCO3
-
]/0.03 x PCO2
• Disadvantages of HH
• Better quantification of resp component than metabolic
• No quantification of non carbonic acids
Henderson-Hasselbalch equation
Expresses the relationship of the HCO3/H2CO3
buffering system to pH

17. Bicarbonate buffer system
• Mixture of:
- carbonic acid (H2CO3) and
- sodium bicarbonate (NaHCO3)
Tremendously efficient becoz of rapid interconversion to volatile CO2
• When pH of solution rises (becomes more alkaline),
the carbonic acid dissociates releasing more H+
which
reduces pH
• When pH of a solution drops (becomes more acidic),
the bicarbonate combines with extra H+
mopping them
up which ensures that pH rises.

18. pH balance regulated by:
1. Chemical buffer system (act immediately)
2. Respiratory centre in brain stem
(1-3 minutes)
3. Renal mechanisms (hours / days)

19. Respiratory system regulation of pH
• Eliminates CO2 from blood whilst replenishing stores of
O2
• CO2 generated by cellular respiration.
• Enters RBC and converted to bicarbonate for transport
in plasma to lungs
CO2 + H2O H2CO3 H+
+ HCO3
-
Carbonic
anhydrase
Carbonic
acid
Bicarbonate
ion

20. pH balance regulated by:
1. Chemical buffer system (act immediately)
2. Respiratory centre in brain stem (1-3 minutes)
3. Renal mechanisms (hours / days)

21. Renal Mechanisms
• Kidneys alter/replenish H+
by altering
plasma [HCO3
-
]
∀↓ [H+
] plasma (alkalosis) → kidneys
excrete lots of HCO3
-
∀↑ [H+
] plasma (acidosis) → kidneys
produce new HCO3
-

22. In acid-base balance, the kidney is responsible for 2 major
activities:
1. Re-absorption of filtered bicarbonate: 4,000 to 5,000
mmol/day
2. Excretion of the fixed acids (acid anion and associated
H+): about 1 mmol/kg/day.
Both these processes involve secretion of H+ into the
lumen by the renal tubule
•Losing a bicarbonate ion is the same as gaining a
hydrogen ion;
•reabsorbing a bicarbonate ion is the same as
losing a hydrogen ion

23. The contributions of the proximal tubules to acid-base
balance are:
•firstly, reabsorption of bicarbonate which is filtered at
the glomerulus
•secondly, the production of ammonium
Daily filtered bicarbonate equals the product of the daily
glomerular filtration rate (180 l/day) and the plasma
bicarbonate concentration (24 mmol/l). This is 180 x 24 =
4320 mmols/day (or usually quoted as between 4000 to
5000 mmols/day).
About 85 to 90% of the filtered bicarbonate is
reabsorbed in the proximal tubule and the rest is
reabsorbed by the distal tubule and collecting ducts

24. Reabsorption of bicarbonate back into the
plasma

25. Bicarbonate Handling… cont.
• BUT secreted H+
is not excreted
• Combines with HCO3
-
in lumen to form CO2
and H2O
• Therefore, filtered HCO3
-
disappears, but
you have some HCO3
-
production inside the
cell from CO2 and H2O
• Gains equal losses so we achieve balance
• Except during alkalosis, the kidneys
reabsorb all filtered HCO3
-
, preventing loss
of HCO3
-
in the urine

26. Addition of New HCO3
-
to Plasma
• What if you use up all filtered HCO3
-
in the lumen,
and you still have free, excess H+
?
– Recombine H+
with another buffer e.g. HPO4
2-
– Excreted as H2PO4
2-
– Gives net gain of HCO3
-
by plasma
• But you can also generate new HCO3
-
to increase
the pH of the plasma
• However, it would be unusual to do this because
you have lots of filtered HCO3
-
to use up first (25
x amount of non-HCO3
-
buffers)

27. Addition of bicarbonate back into the plasma
by secretion of H+

28. Another way of making HCO3
-
…..
• Renal production and secretion of ammonium (NH4
+
)
• Urinary H+
excretion = renal addition of new HCO3
-
to
plasma

29. Renal responses to acidosis
• H+
ions secreted to reabsorb all filtered HCO3
-
• Even more H+
secreted, contributing new HCO3
-
to
plasma as these H+
ions are excreted bound to
non-HCO3
-
urinary buffers such as HPO4
2-
• Tubular glutamine metabolism and ammonium
excretion are enhanced to make more HCO3
-
(TAKES TIME!!!)
• NET RESULT: More new HCO3
-
into blood,
increasing plasma [HCO3
-
]. This compensates for
the acidosis. Urine is highly acidic (lowest pH is
4.4)

32. The response to alkalosis

33. Traditional versus modern
views of blood gas analysis

34. Traditional view
When we first study acid-base balance, it is too easy
believe that the concentrations of the hydrogen and
bicarbonate ions, [H+] and [HCO3-], are at the heart
of the problem - are dominant forces.
We do, after all, discuss them, measure them, and
treat them:
Whatever an acid or a base does, must be due to the
pH, i.e., the concentration of H+.
In addition [HCO3-] must surely determine the
metabolic state.

35. Disadvantages of the traditional view
in the critically ill
Failed to take into account contributions of
albumin in calculation of anion gap/SBE
Unsatisfactory explanations for changes in
pH with fluid (saline) administration

36. Stewart (1981): physical chemical
approach
• Concept of electrolytes as
critical factors in acid/base
balance
• Balance of SID is
maintained by the
dissociation and
reassociation of water

37. Stewart's Independent Variables:
There are three variables which are
amenable to change in-vivo:
1. partial pressure of carbon dioxide (PCO2),
2. total weak non-volatile acids [ATOT],
3.net Strong Ion Difference [SID].
The influence of these three variables can
be predicted through six simultaneous
equations

38. Stewart's Dependent Variables:
Stewart listed a total of six ion
concentrations as dependent:
[H+], [OH-], [HCO3-], [CO3--2], [HA], [A-]
(weak acids and ions).
In-vivo and clinically, therefore, these are
not subject to independent alteration.
Their concentrations are governed by
concentrations of other ions and
molecules.

40. Na+Na+
K+K+
Ca++
, Mg++Ca++
, Mg++
Cl-Cl-
XA-XA-
HCO3
-HCO3
-
Albx-Albx-
Piy-Piy-
SID eff
Strong
cations
Strong
anions
SID apparent =
Strong cations
+
Strong anions

41. Na+Na+
K+K+
Ca++
, Mg++Ca++
, Mg++
Cl-Cl-
XA-XA-
HCO3
-HCO3
-
Albx-Albx-
Piy-Piy-
Strong
cations
Strong
anions
SID eff
Strong ion
gapSID apparent =
Strong cations
+
Strong anions
SID
effective

42. [SID]:
The Strong Ion Difference is the difference
between the sums of concentrations of the strong
cations and strong ions:
[SID] = [Na+] + [K+] + [Ca2+] + [MG2+] - [CL-]
– [Other Strong Anions].

43. [ATOT]:
[ATOT] is the total plasma concentration of
the weak non-volatile acids, inorganic phosphate,
serum proteins, and albumin:
[ATOT] = [PiTOT] + [PrTOT] + albumin.

44. Total CO2:
Predominantly pCO2, also H2CO3, carbonates
The effects of changes on PCO2 are well understood
and produce the expected alterations in [H+]:
CO2 + H2O <—> H2CO3 <—> HCO3- + H+

45. Metabolic (Non-Respiratory):
Metabolic disturbances, obviously, cannot be viewed as a
consequence of bicarbonate concentration because
bicarbonate is merely a dependent variable.
The two possible sources of metabolic disturbances are either
[SID] or [ATOT].
With normal protein levels, [SID] is about 40mEq/L
Any departure from this normal value is roughly equivalent to
the standard base excess (SBE), i.e., if the measured [SID]
were 45 mEq/L, the BE would be about 5 mEq/L, and a
measured [SID] of 32 mEq/L would approximate to a BE = -8
mEq/L.

46. Changing [SID]:
[SID] can be changed by two principal methods:
1) Concentration:
•Dehydration or over-hydration alters the concentration
of the strong ions and therefore increases, or decreases,
any difference.
•The body's normal state is on the alkaline side of neutral.
•Therefore, dehydration concentrates the alkalinity
(contraction alkalosis) and increases [SID];
•Overhydration dilutes this alkaline state towards neutral
(dilutional acidosis) and decreases [SID].
2) Strong Ion Changes:
If the sodium concentration is normal, alterations in the
concentration of other strong ions will affect [SID]:

47. 2) Strong Ion Changes:
If the sodium concentration is normal, alterations in the
concentration of other strong ions will affect [SID]:
a. Inorganic Acids:
The only strong ion capable of sufficient change is
chloride, Cl- (potassium, calcium and magnesium do
not change significantly). An increased Cl- concentration
causes an acidosis and a decreased [SID] causes
alkalosis.
Because the chloride ions are measured, the anion gap
will be normal.
b. Organic Acids:
By contrast, if the body accumulates one of the organic
acids, e.g., lactate, formate, keto-acids, then the
metabolic acidosis is characterized by a normal chloride
concentration and an abnormal anion gap because of the
presence of the "unmeasured" organic acid.

49. Changing [ATOT]:
The non-volatile weak acids comprise inorganic phosphate,
albumin and other plasma proteins. Making the greatest
contribution to acid-base balance are the proteins, particularly
albumin, which behave collectively as a weak acid.
Hypoproteinemia, therefore, causes a base excess and vice
versa.
Phosphate levels are normally so low that a significant fall is
impossible. However, in renal failure, high phosphate levels
contribute to the acidemia.

50. Pros and Cons:
1) Understanding:
Stewart's greatest contribution may be his focus on the
importance of the factors controlling pH.
[H+], [OH-] and [HCO3-] are merely dependent
variable.
This emphasis on the importance of the underlying
causes rightly diminishes the importance of the
bicarbonate ion.

51. 2) Shortcomings :
A major shortcoming lies in calculating a value for
[SID] which depends upon accurate measurements of
several variables.
An acceptable level of error in the underlying
measurements becomes less acceptable after
subtraction.
This is partly because the errors are summed and
partly because any error now appears proportionately
large against the resulting small value.

52. 3) Standard Base Excess Accuracy:
Standard base excess has been well validated both for
accuracy and for clinical relevance through many
years of familiarity and clinical correlation.
Albumin correction:
AG corrected=AG OBSERVED+ 2.5 (4.2-observed
albumin)

53. Clinical application facilitated by
determination of 4 variables
1. The SBE from blood gas analysis
2. The SBE effect from NaCl: ( Na- Chl-38)
3. The BE effect of albumin: 2.5(4.2-obs albumin)
4. The BE effect of unmeasured anions (UMA)

54. Which Model to Use?
• Ultimately personal preference!
– All models are simply a means of explaining
observed physical findings
– All models have inbuilt assumptions and
limitations … to varying degrees
• IF you choose to rely upon a more simple
model, this is reasonable, providing:
– The model ‘works’ for the majority of clinical
scenarios
– You are aware of the limitations of the model
– You are aware of the existence of more accurate
models, when they exist.

55. SIDS and effects of fluid administration
Critical Care 2005, 9:204-211
Stewart's quantitative physical chemical approach enables us
to understand the acid–base properties of intravenous fluids.
Lowering and raising plasma SID while clamping ATOT cause
metabolic acidosis and alkalosis, respectively.
Fluid infusion causes acid–base effects by forcing
extracellular SID and ATOT toward the SID and ATOT of
the administered fluid.
Thus, fluids with vastly differing pH can have the same acid–
base effects.
The stimulus is strongest when large volumes are
administered, as in correction of hypovolaemia, acute
normovolaemic haemodilution, and cardiopulmonary bypass.

56. Saline, SID and Stewarts

60. Henderson-Hasselbalch
theory
Stewart’s approach

61. Conclusion:
For most acid-base disturbances, and for the foreseeable
future, the traditional approach to acid-base balance seems
certain to prevail.
For the clinician, the three variables of greatest us are the
pH, PCO2,and standard base excess (SBE).
What might change this?
The answer would have to be published cases where clinical
management has been critically improved by using Stewart's
approach.
Such cases would have to be accumulated, evaluated, and
approved before any major switch to his approach seems
warranted.

62. Useful Websites
• Mainly Traditional + History + Terms
– http://www.acid-base.com/
• Traditional & Stewart
– http://www.qldanaesthesia.com/AcidBaseBook/
ABindex.htm
• Stewart Approach
– http://www.anaesthetist.com/icu/elec/ionz/Stewart.ht
http://www.AcidBase.org