A general approach

The physico-chemical acid-base approach is different from the conventional approach based
on the Henderson-Hasselbalch equation, and requires a new way of approaching acid-base
problems. At any one point in time, the [H
+
] is determined by the composition of the
electrolytes and the PCO
2
of the solution. Mathematical analysis shows that it is not absolute
concentrations of almost totally dissociated ("strong") ions that influence hydrogen ion
concentration, but the difference between the activities of these strong ions (This "strong ion
difference" is commonly abbreviated "SID"). We have already displayed the relationship
between SID and [H
+
] as well as [OH
-
], but let's sketch the two on the same set of axes:

We are now ready to approach acid-base using a physico-chemical model. A very simplistic
way of approaching acid-base problems is to think of H
+
and OH- as charge buffers. Any
change in the charge composition of a solution will result in a change in H
+
or OH- to
maintain electroneutrality. For instance, an increase in the negatively charged chloride will
result in an increase in H
+
to maintain electroneutrality. This increased [H
+
] we call
'acidosis'. Because of the inverse relationship between H
+
and OH-, it is sometimes easier to
assess pH changes through changes in the basic OH-. Increased OH- leads to alkalosis,
decreased OH- results in acidosis. For example, the problem of hyperchloremia can be looked
at in another way using OH-. The increased Cl- will decrease the SID. The SID is normally
positively charged so that the decreased SID would result in fewer OH-. Fewer of the basic
OH- results in acidosis. The following picture is a simplified rendering of normal acid-base
status in plasma. We will explore changes in acid-base balance using this illustration:
Note that the
above picture is used to provide a conceptual framework for discussion, and is not intended to
replace the more detailed analysis of acid base that we previously attempted.

Specific Metabolic abnormalities
From the above general approach more specific metabolic problems can be addressed.
Metabolic problems arise from abnormalities in either
1. SID, or
2. weak acid.
The weak acids are primarily composed of proteins and phosphate. These weak electrolytes
are partially charged thus any change in pH is brought about only by the charged portion of
that change. Thus, change in protein or phosphate is tempered by the partial contribution that
they make to the electroneutrality equation. This means that most acute acid-base metabolic
changes are a result of change in the SID. There are three general mechanisms by which SID
changes:
1. changing the water content of plasma (contraction alkalosis and dilutional acidosis)
2. changing the Cl- (hyperchloremic acidosis and hypochloremic alkalosis), and
3. increasing the concentration of unidentified anions (organic acidosis).
Let's systematically explore the ways that SID changes.
1. Free water change - Dilutional acidosis and contraction alkalosis
o Dilutional Acidosis
Classically a dilutional acidosis is explained as an expansion of the
extracellular volume by a solution without alkali. This expansion dilutes the
concentration of HCO3- buffer. This dilution of the HCO3- results in the
acidosis. This explanation does not explain why a similar dilution of the H
+

does not take place.
The physico-chemical approach explains the phenomena differently. Changing
the amount of free water concentrates or dilutes the electrolytes. By changing
the relative concentration of the electrolytes, a dilutional acidosis or
contraction alkalosis can result. This change results from change in SID.
Development of a dilutional acidosis is best illustrated by an example. If a liter
of water contains 140 mEq/L of sodium and 110 mEq/L of chloride than the
SID of that solution is 30 mEq. If we were to add another liter of water
without adding any more electrolytes, the solution would contain 70 mEq/L of
sodium and 55 mEq/L of chloride. Now, the SID is 15 mEq. Because we have
decreased the positive charge contribution of the SID from 30 to 15 mEq, a
fall in OH- would occur and a "dilutional" acidosis would be seen. This
explanation is easily understood by considering the following diagram:
In the operating room, dilutional acidosis can theoretically occur as part of the
TURP syndrome. Studies of the TURP syndrome have focused on dilutional
hyponatremia however this should also be accompanied by an acidosis if the
chloride is equally diluted. Traditional treatment of the hyponatremia focuses
on treatment with normal or hypertonic saline. Analysis of this treatment
reveals that this may not be the best method of managing this problem. If we
were to take one liter of our solution with 70 mEq/L of sodium and 55 mEq/L
of chloride and add one liter of normal saline which has 154 mEq/L of Na+
and 154 mEq/L of Cl-, we would increase our sodium concentration but
worsen our acidosis. A beaker of this solution would contain 112 mEq/L of
sodium and 105 mEq/L of chloride with an SID of 7 mEq. This further decline
in the SID results in a decline in the OH- charge buffer and further acidosis. A
more appropriate treatment might be with sodium bicarbonate . Here, sodium
ions are administered with HCO3-. The bicarbonate is conveniently expired
through the lungs leaving the Na+ to increase the SID.

Let's further explore the result of adding normal saline to plasma, in the
following diagrams:



Combining the two clearly causes an acidosis:


Contrast this with the consequences of adding Ringer's lactate:



Note how, in contrast to normal saline, the Ringer's causes minimal disturbance
in acid-base balance:

In the above we assume that (as normally occurs) the lactate is fully
metabolised in the liver. This may not apply in severely ill patients, especially
those with substantial liver disease.


o Contraction alkalosis
Contraction alkalosis can be seen in the patient who has been fluid restricted
or treated with diuretics. Similar to dilutional acidosis, this problem arises
from free water and SID changes. Consider the extreme case where we take
the original liter of water containing 140 mEq/L of sodium and 110 mEq/L of
chloride and boil off half of the water. This results in a sodium concentration
of 280 mEq/L and a chloride concentration of 220 mEq/L. Now the SID is 60
mEq, and the OH- "buffer" would increase so that the solution would remain
electrically neutral. Treatment of contraction alkalosis simply requires free
water administration in the form of hypotonic solutions.

Using the beaker model, treatment can be explained mechanistically. We
would now add one liter of 0.45% NaCl solution containing 77 mEq of Na+
and 77 mEq of Cl-. The final electrolyte concentration would contain 145 mEq
of Na+ and 125 mEq of Cl- and an SID of 20 mEq. By the use of this fluid we
have changed the SID from 60 to 20 mEq resulting in a decrease in the OH-
and in fact an over-correction of the alkalosis!
2.
3. Chloride changes
o Hypochloremia
Chloride shifts occur in relation to gastrointestinal abnormality. If the
hyperchloric gastric contents are lost through vomiting or through gastric tube
suction then a hypochloremia can result. Hypochloremia leads to an increase
in SID. The positive charge increase associated with the SID must be balanced
by an increase OH-.
Administration of normal saline constitutes effective treatment. This treatment
can be illustrated in the same fashion as free water changes. If we have a one
liter beaker of water with 140 mEq/L of Na+ and a "hypochloremic" 95
mEq/L of Cl- then the SID is 45 mEq. If one liter of normal saline is added,
the beaker would then contain 147 mEq/L of Na+ and 125 mEq/L of Cl- with
the SID being 22 mEq/L. By shifting the SID, we have shifted the pH in the
normal direction. If volume expansion is problematic then potassium, calcium
or magnesium chloride can be administered. The tight regulation and small
concentration of these cations makes them beneficial under these
circumstances. Similarly to NaHCO3, Cl- could also be administered
essentially by itself in the form of hydrochloric acid (HCl), although most
clinicians would shy away from this approach!

o Hyperchloremia
Hyperchloremia results in an increase in H
+
. Treatment of the elevated Cl-
and decreased SID would be done by increasing the SID. This could be
accomplished through sodium bicarbonate administration. Here, the Na+ is the
effector agent and not the HCO3-. The HCO3- is a dependant variable and is
rapidly excreted as CO2. Other ways of administering Na+ with a
metabolizable anion are through the use of the sodium salts of lactate,
gluconate, acetate or citrate. Volume contraction would also counter the fall in
SID but is neither desirable nor easily effected.

4.
5. Unidentified anions
SID can also be affected by the presence of organic acids such as lactate or ketoacids.
Again, because these negatively charged molecules lower the SID, they result in an
acidosis. Treatment is usually focused on stopping the production of acid. Resolution
of the abnormal H
+
can also be achieved by increasing the SID using NaHCO3.