Renal Physiology

Acid Base

Part 3

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 Acid-Base Physiology
Fall 2009

Learning Objectives

1. Define: pH, acid, base, alkalosis, acidosis, alkalemia, acidemia. Identify the normal
range of pH values, and the upper and lower limits compatible with life.
2. Describe the role of buffers in maintaining pH, including the roles of the lungs and
kidneys.
3. Describe the respiratory and renal regulation of the CO2/HCO3- buffer system,
which allows a buffer with a pKa of 6.1 to be physiologically important in the
maintenance of the normal plasma pH of 7.4.
4. Calculate the renal filtered load of HCO3-, and identify the major sites of
reabsorption (and secretion) along the nephron, emphasizing the importance of H+
secretory mechanisms in this process. Describe the cellular mechanisms responsible
for net transepithelial movement of HCO3-.
5. Describe net acid excretion by the kidneys, titratable acid, the importance of urinary
buffers, and the production and excretion of ammonium. Distinguish between the
reclamation of filtered bicarbonate and the formation of new bicarbonate.
6. Describe how alterations in systemic acid-base balance result in changes to the
filtered HCO3- load and tubular H+ secretion. Distinguish this from factors that alter
this process (e.g. ECF volume changes, aldosterone levels)
7. Describe processes that lead to acid-base disturbances and list common causes
8. Define base excess (or deficit) and anion gap
9. Explain what is meant by primary and secondary acid base disturbances using the
concept of “compensation”.
10. From blood values, identify simple and mixed metabolic and respiratory acid-base
disturbances.

2
Overview
As with most ions in ECF, renal excretion is central in the regulation of H+ balance.
However, acid-base balance is complicated by interactions with numerous buffer systems
and with CO2 balance via the pulmonary system. The primary variables to consider in most
clinical situations are pH, PaCO2 and [HCO3-]. Normal values of 7.40, 40 mmHg and 24
mEq/L respectively must be known at the outset in order to interpret clinical problems.
This section will consider the roles of buffers, alveolar ventilation and renal excretion as the
3 lines of defense against acid/base changes.

Consider the following case:

Is there an acid base abnormality?
What is/are the causes?
What other information do we need?

At present you may not be able to identify the acid base balance shown below but by the
end of this section you should be able to identify the normal values for PaCO2 HCO3 and
base defecit. These will assist in determining an acid base disturbance and its possible
cause and possible compensation.

Case #1
• 26 YO male involve in MVC
• Hypotensive and tachycardia at crash scene
• Altered mental status and multiple severe
injuries
• pH = 7.38; PaCO2 = 30 mm Hg; HCO3- = 18
mEq/L, Base Deficit = -8 mEq/L

3
Definitions
Acids are molecules that release hydrogen ions in solution. Bases are ions or molecules that
can accept hydrogen ions.
Definitions The term alkali is often used
interchangeably with base,
but strictly speaking refers to
• Acid: proton (H+) donor combination of alkaline
metals (sodium, potassium,
HCl ↔ H+ + Cl- lithium etc) with a strong
base like hydroxyl ions.
H2O + CO2 ↔ H2CO3 ↔ H + + HCO3-
Strong acids rapidly
• Base: proton acceptor dissociate releasing large
amounts of H+, weak acids
NaOH + H+ ↔ Na+ + H2O partially dissociate, releasing
less H+. Strong bases react
+
NH3 + H ↔ NH4 +
rapidly and strongly to
neutralize H+, weak bases
bind H+ much more weakly.
Physiologically most acids
and bases are weak.

The [H+] of ECF is very low (0.00004 mEq/L = 40 nEq/L). Normal variations are a
remarkably small 3-5 nEq/L. It is customary to express these very small numbers using the
logarithmic pH scale:

A 10 fold H+ concentration
Definitions change represents a 1 unit
pH change. A 2 fold H+
pH = “power of hydrogen” concentration change
represents approximately a
pH = - log10 [H+]
0.3 unit pH change. The
limits of ECF pH
When [H+] = 10-7 mol/L: compatible with life are
around 6.8 to 7.8. pH is
pH = - log (10-7) = log (1/10-7) = log 107
normally regulated in the
pH =7 range 7.38 to 7.42. pH must
be finely regulated because
pH change of 1 = 10X change in [H+] altered [H+] results in
changes in protein structure
(e.g. enzymes, receptors,
membrane transporters,
structural proteins etc)

4
Sources of H+ and lines of defense
Intake and metabolism of a typical Western diet results in the formation of around 15 000
mmoles of “volatile acid” (CO2) per day plus around 70 mmoles of non-volatile (“fixed,”
“metabolic” acids) including organic acids, phosphoric and sulphuric acids. To achieve
balance, there is net excretion of CO2 at the lung and usually net H+ excretion by the
kidneys. The first (immediate) defense against changes in pH comes from the presence of
buffers. Changes in ventilation, occurring in seconds to minutes alter CO2 excretion quickly
as the second line of defense to pH change.

The renal system is the final line of defense acting to prevent sustained pH change, acting
over hours to days.

Buffers

A buffer is any substance that

Buffers Are The1st
Line Of Defense. They can reversibly bind hydrogen
ions. The effectiveness of a
Minimize (But Do Not Prevent) Changes In pH. buffer system is measured as
buffering power (defined as the
number of moles of strong acid
Buffer + H+ ↔ HBuffer added to 1 liter of solution to
reduce pH by 1 unit” OR “moles
“Buffering Power” (β) = ∆[strong acid] / ∆pH of strong base added to 1 liter of
solution to increase pH by 1
unit). The largest chemical
buffering power is associated
with intracellular proteins.
However, in ECF the
bicarbonate buffer system is
most important.

The Bicarbonate Buffer System

In the presence of the enzyme carbonic anhydrase, dissolved carbon dioxide reacts with
water to form carbonic acid:

CO2 + H2O ↔ H2CO3

Carbonic acid is a weak acid that dissociates to form bicarbonate and hydrogen ions:

CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+

Since the ratio of CO2 : H2CO3 is about 400:1, the full equilibrium reaction is usually
shortened to the “pseudo-equilibrium:”

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CO2 + H2O ↔ HCO3- + H+

Henderson-Hasselbalch Equation
For the purists, here is the derivation of the HH equation (not in the objectives!). So for
those of you who are reading this here it comes. Otherwise skip to the last paragraph of this
section.

A dissociation constant for the forward reaction of acid formation, Ka, may be written:

Ka = [H+] x [HCO3-] / [CO2]

Rearranging for [H+]:

[H+] = Ka x [CO2] / [HCO3-]

Since [CO2] = PCO2 x solubility (s) :

[H+] = Ka x (s. PCO2) / [HCO3-]

Taking the negative logarithm of all terms and separating the terms on the right:

-log[H+] = -logKa -log {(s. PCO2) / [HCO3-]}

Which is the same as:

pH = pKa -log {(s. PCO2) / [HCO3-]}

and inverting the fraction (s. PCO2) / [HCO3-]:

pH = pKa + log [HCO3-] / (s.PCO2)

Welcome back ! Given that pKa = 6.1 and s = 0.03 millimoles/mmHg, inserting normal
values of 24 mEq/L for [HCO3-] and 40 mmHg for PCO2, the Henderson-Hasselbalch
equation correctly predicts a normal plasma pH of 7.4.

What Is The Central Message Of Henderson-

Hasselbalch?
Since in most clinical
pH = pKa + log(HCO3- / s.PCO2) situations, the HH equation
provides a good estimate of
Plasma pH is a simple function of the HCO3- : PCO2 ratio plasma pH, it follows from
the equation that changes in
pH are usually a simple
HCO3- : PCO2 ↑ = Alkalosis : Is it HCO3- ↑ or PCO2 ↓ ?

HCO3- : PCO2 ↓ = Acidosis : Is it HCO3- ↓ or PCO2 ↑? 6

function of the HCO3 : PCO2 ratio. If the ratio increases, pH increases (ALKALOSIS),
which could occur either due to a rise in HCO3- (metabolic alkalosis), or a fall in PCO2.
(respiratory alkalosis). If the ratio decreases, pH falls (ACIDOSIS), which could be due
either to a fall in HCO3- (metabolic acidosis) or a rise in PCO2 (respiratory acidosis).

The buffering power of a closed buffer system has a Normal distribution, with its peak at
pKa. Hence, the bicarbonate buffer system operates a long way from its pKa of 6.1 in
plasma of pH = 7.4, and yet is the most powerful ECF buffer. Why is it so ? The reason for
this paradox is that this buffering system is “open.” If we are talking about the bicarbonate
buffer system in a „test-tube‟ it has its greatest buffering power at a pH of 6.1; this is a closed
system where both CO2 and HCO3 ions can build up respectively therefore altering
equilibrium rates. However, we are talking about this buffer system working in a
physiological system where it is termed an „open‟ system as the amounts of CO2 and HCO3
can be regulated. Regulation of CO2 by the lungs and HCO3 by the kidney confers the
functional buffering power observed. For example, if strong acid was added to blood, the
buffer reaction moves toward CO2 formation. In a closed system, build up of CO2 rapidly
prevents buffering of additional H+. In vivo a build up of CO2 does not occur due to
increased ventilation and CO2 excretion. In this open system, the additional H+ is effectively
buffered (albeit at the cost of consuming HCO3-).

7
Respiratory Regulation of Acid Base Balance
The second line of defense against acid base changes is control over ECF CO2 concentration
by the lungs. Normal pulmonary function balances CO2 excretion with metabolic CO2
production. As shown in the figure below, increased ventilation decreases ECF [H+] (raises
pH), whereas decreased ventilation increases ECF [H+] (lowers pH). These changes occur
rapidly through the bicarbonate buffering equilibrium.

Respiratory System is the Second Line of Defense

Non-linear !

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-

Diagram after A Guyton

Ventilation Rate Responds Strongly To Acidemia

Not only does the alveolar ventilation rate influence pH by changing PCO2, but the pH in
turn affects the rate of ventilation. The figure shows that an acid stimulus is especially
effective at increasing the rate of ventilation and CO2 elimination. Recall that the presence of
H+ sensors in peripheral chemoreceptors can explain this ventilatory response to the
presence of excess metabolic acid. CO2 sensing in both peripheral and central
chemoreceptors should prevent acidemia resulting from volatile acid (CO2) accumulation,
assuming there is normal pulmonary function.

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Renal Contribution To Acid Base Balance

The metabolic acid load of

Cellular respiration produces around 70 mmole/day is
CO2 and “metabolic acids” buffered by the bicarbonate
buffering system, so that
ECF each hydrogen ion consumes
Buffering one bicarbonate. This is
Cells metabolic acid
Food H+ + HC03- converted to carbon dioxide,
consumes ECF
HC0-3
which is excreted at the
lungs. Thus, there is net loss
CO2
of plasma bicarbonate from
CO2 the body as metabolic acids
CO2 are buffered. 70 mmole of
bicarbonate per day is
equivalent to about one fifth
of total extracellular
Lung bicarbonate, which must be
replenished to maintain acid-
base balance.

The kidney has two major functions that contribute to acid-base homeostasis. The first is
regulation of plasma bicarbonate concentration. Under physiological conditions the kidney
maintains plasma [bicarbonate] between 22-26 mEq/L. The kidney can excrete bicarbonate
to reduce plasma bicarbonate, or can generate new bicarbonate to increase plasma
bicarbonate. Under most circumstances, the kidney delivers more bicarbonate to the ECF
via the renal vein than it receives via the renal artery. The amount of bicarbonate added is
just sufficient to neutralize net acid production as a result of cellular metabolism. The second
major (related) function is net acid excretion to combat production of metabolic acids. Acid
in the urine is mainly in the form of ammonium ions (NH4+) and phosphoric acid (H2PO4-).

Recovery Of Filtered Bicarbonate

Prior to any fine regulation of

Acid secretion in the proximal acid-base balance, the renal
tubule recovers filtered HCO3- tubule must recover the
filtered load of bicarbonate. If
Lumen Blood plasma [bicarbonate] is 24
filtration
Na+ mEq/L and GFR is 180
3Na+
HCO3- NHE3 L/day, the filtered bicarbonate
H+ 2K+ load is 4320 mEq/day. The
majority of filtered
H2CO3 Na+
H2CO3 bicarbonate is recovered in the
CA H 2O
+
NBC
early proximal tubule.
3HCO3-
H2O+ CO2 CO2
CA

CA = carbonic anhydrase (X acetazolamide) 9

Hydrogen ion is secreted into the tubule lumen mainly via the Na/H ion exchanger NHE3.
Hydrogen ion combines with filtered bicarbonate to form carbonic acid, which in turn is
rapidly converted into carbon dioxide and water, catalyzed by carbonic anhydrase, which is
anchored on the extracellular face of the brush border membrane. The high PCO2 produced
at the luminal cell surface results in diffusion of carbon dioxide into the proximal tubule cell.
The carbon dioxide that enters the cell is rehydrated to form carbonic acid by the action of
cytoplasmic carbonic anhydrase. This releases bicarbonate, which enters the blood via a
Na/HCO3 cotransporter known as NBC in the basolateral membrane. Hydrogen ion
generated at the same time as cytoplasmic bicarbonate is available for secretion into the
lumen and combination with further filtered bicarbonate. Note the net action of this
mechanism is reabsorption of Na bicarbonate. NO NET ACID EXCRETION OCCURS.
Ammonium Excretion

Ammonium is synthesized in
Acid is also excreted as ammonium ions, mitochondria primarily in proximal
which further replenishes ECF HC03 - tubule. Deamidation of glutamine
and deamination of gutamate both
lumen blood
produce ammonia as a biproduct. At
glutamine pH=7.3 (typical intracellular pH) the
NH4+ vast majority of ammonia is
NH4+ converted to NH4+, thereby
2HCO3-
Na+ glutamic acid consuming free hydrogen ion. NH4+
is secreted as an alternate substrate
NH4+
NH3 to hydrogen ion at the apical
-ketoglutarate membrane Na/H ion exchanger.
Though some NH4+ is reabsorbed
Proximal/distal tubules
from the filtrate in the loop of
Henle, most remains in tubular fluid
and is excreted in the urine. Deamination of glutamate also yields 2 bicarbonate ions, that
leave the cell across the basolateral membrane. Thus the net effect of this model is excretion
of hydrogen ion, plus generation of new bicarbonate.

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“Titratable Acid” Excretion

The slide shows the mechanism for

Excretion of “titratable acid” excretion of titratable acid. One
generates new HC03- important difference compared to
the mechanism of bicarbonate
Lumen Blood
filtration recovery from the filtrate is that
Na+
NHE3
3Na+ secreted hydrogen ion is not
recycled. In this case it is buffered
HPO42- H 2K+
+
by alkaline phosphate ions in the
Na+ filtrate and the hydrogen ion is
H O H2CO3 NBC
H2PO4- +
2 excreted in urine by incorporation
3HCO3-
CO2 into acid phosphate ions. The other
CA
key feature of the model is that the
secreted hydrogen ion is derived
Proximal tubule cell
from carbonic acid in the cell
cytoplasm, which generates
bicarbonate at the same time. Bicarbonate leaves the cell via the basolateral membrane to
enter the blood. The net effect of this model is to excrete hydrogen ion and make a “new”
bicarbonate ion (i.e. one that was not in ECF previously). The model describes events in the
proximal tubule, where the largest quantity of hydrogen ion is secreted, though it should be
realized that hydrogen ion secretion continues in the loop of Henle and all along the distal
nephron and collecting duct. The fraction of acid excretion as phosphates is called titratable
acid because titration of urine to the plasma pH of 7.4 does not include H+ associated with
ammonium ions, since the pKa of the NH4 ↔ NH3 + H+ equilibrium is 9.2.

In the late distal tubule and collecting duct, available buffers are at a low concentration and
further hydrogen ion secretion requires active transport mechanisms. Continued active
hydrogen ion secretion now causes luminal pH to fall substantially.

Acidification of the urine takes place all along the nephron. The greatest quantity of
hydrogen ion is secreted in the proximal tubule, though pH only falls to 6.8 here because of
the large amount of buffers in glomerular filtrate. The loop of Henle, distal tubule and
cortical collecting duct principal cells all secrete H+ via Na/H ion exchangers in the apical
membrane, accounting for the fall in luminal pH at these sites. Aldosterone responsive cells
in these areas increase Na/H ion exchange when stimulated by aldosterone.

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 In the collecting duct H+ is In the collecting duct most of the
secreted up a steep gradient buffers have been used, so that
Intercalated cells
further H+ secretion causes marked
reduction of luminal pH. Sustaining
pH=7.4 , A H+ secretion now requires primary
H+
PT ATP
HCO3 -
active H+ transport. Alpha-
pH=6.8 K +
Cl- intercalated cells express two H+-
LOH H +
ATPases, one of which is H/K-
pH=6.0
ATPase, mentioned earlier as a
DT ,B transporter that is activated during
ATP
+ Cl-
H+ potassium depletion to scavenge
CD pH=5.5 HCO3- remaining potassium from the
to 4.5
filtrate. The other type of cell is the
Beta intercalated cells which are
bicarbonate secreting. If there fall in plasma pH, more H+ pumps are placed in the apical
surface of the alpha intercalated cells. Conversely, a rise in plasma pH favors the secretion
of HCO3 from beta intercalated cells. The secretion of HCO3 from beta intercalated cells is
relatively minor in comparison to the quantities of HCO3 that are filtered, reabsorbed
and/or created in the proximal tubule.

Renal Correction of Acid Base Disturbances

We have seen that net acid excretion by the nephron is linked to regeneration of
bicarbonate. Net acid excretion is equal to the sum of NH4+ and H2PO4- excretion, minus
bicarbonate excretion. The typical profile of net acid excretion for an individual in acid-base
balance is 75% of net acid excretion in the form of NH4+ and the remainder being titratable
acids.

In the case of acidemia, the renal system increases H+ secretion, and therefore HCO3
reabsorption and HCO3 regeneration. If the cause is of metabolic origin, buffering of fixed
acids reduces plasma HCO3 concentration, resulting in a low filtered HCO3 load. More of
the H+ secreted into the tubule lumen is available for net acid excretion, coupled to new
HCO3 generation to cure the problem. If the cause is respiratory, with high PCO2, the same
effects occur, leading to normalization of plasma pH, at the expense of excess plasma HCO3.
Chronic acidosis of any origin causes a large increase in renal ammoniagenesis.

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During alkalosis NH4+ and H2PO4- excretion continues at a reduced rate, but overall net acid
excretion is negative due to a rise in bicarbonate excretion. In metabolic alkalosis, high
filtered HCO3 load is an important source of renal HCO3 excretion. In the case of
respiratory alkalosis, the renal response is to reduce tubular H+ secretion, allowing more
filtered HCO3 to escape and reducing new HCO3 generation into the blood.

Hydrogen and Potassium Interactions

Recall the general interaction of H+ and K+ with respect to intracellular buffering. This is by
far the most dominant mechanism determining H+ and K+ interactions as it occurs
throughout all cells. In addition there is an important quantitative relationship between renal
H+ and K+ excretion, linking homeostasis of these ions. The interaction between H+ and K+
is complex with many process‟ occurring simultaneously.

In many situations there is a reciprocal relationship between H+ and K+ secretion in the

collecting duct. The basis of this
In general H+ and K+ secretion in the reciprocal interaction between H+
collecting duct change reciprocally and K+ is partly the presence of
the exchange H+/K+-ATPase in
Acidosis intercalated cells of the collecting
duct. In an acidotic state
H+ H+ intercalated cells are secreting
Hyperkalemia
increased H+ therefore the
K+
K +
reciprocal rate of K+ reabsorption
Alkalosis is increased leading to a NET
reduction in K+ secretion. This
can potentially cause acidotic
K+ depletion
hyperkalemia. In an alkalotic state,
H+ secretion falls, therefore the
reciprocal rate of K+ reabsorption
+
is decreased leading to a NET increase in K secretion. This can cause the development of
K+ depletion and an alkalotic hypokalemia. In response to K+ depletion there is an increase
in the number and activity of the H+/K+ exchanger resulting in increased H+ secretion and
the development of hypokalemic alkalosis. In spite of the effects mentioned above the most
significant factor in determining H+ and K+ relations is the buffering within cells. (This
was discussed on page 52 of Part II of your notes). Briefly, if cells are attempting to buffer
an acidosis, K+ is released, lowering intracellular K+ and reducing K+ availability for
secretion. Conversely, when cells are reacting to hyperkalemia: H+ ions are released and
reducing H+ availability for secretion.

One more factor that should be mentioned is the effect of pH on the activity of the
basolateral Na+/K+ ATPase pump and ROMK channels in principal cells. Decreasing
intracellular pH from acidemia inhibits the Na+/K+ ATPase pump reducing intracellular
K+. (This is a direct effect of pH on the ATPase activity). Furthermore, the reduced
intracellular pH in principal cells reduces the permeability of the apical ROMK channels to
K+ ions (again this is a direct effect of pH). These combined effects in the principal cells

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(reduced Na/K ATPase and ROMK activity) contributes to the hyperkalemia seen in
acidosis.

Interaction Between ECF Volume And Acid Base Balance

Recall that defense of effective circulatory volume is a dominant process. As a consequence
of this there are „side-effects‟ related to H+ and K+ balance form maintaining an effective
circulating volume. Low ECV is associated with lower GFR and increased fractional Na+
reabsorption, including increased proximal tubule HCO3 reabsorption. Low ECV is also
accompanied by increased aldosterone, which stimulates Na/H exchange in distal nephron
(as a means of increasing Na reabsorption), thereby increasing net acid excretion. The result
of sustained low ECV can be metabolic alkalosis also termed volume contraction alkalosis.

Clinical Diagnosis of Acid Base Disorders

Clinical Definitions
The slide shows clinical definitions of acid base disturbances. Base excess (or base deficit) is
a way of estimating the metabolic contribution to an acid base problem. Base excess
expresses the amount of strong acid (or base) in mEq/L needed to titrate the pH of 100%
oxygenated blood to 7.4 at 37oC and at a PCO2 of 40 mmHg. It is a calculated value,
requiring a complex algorithm, the idea behind which is to assess the size of a metabolic
disturbance independent of PCO2, by first estimating what the pH would be if PCO2 was
corrected to 40 mmHg. Base excess is generally considered more useful than simply using
the HCO3 concentration, since this is never truly independent of PCO2.

Clinical Definitions and Diagnostic Aids

• Respiratory acidosis = PaCO2 > 45 mmHg

• Respiratory alkalosis = PaCO2 < 35 mmHg
• Metabolic acidosis = HCO3- < 22 mmHg or Base
Deficit of < -2
• Metabolic alkalosis = HCO3- > 28 mmHg or Base
Excess of > +2

Anion Gap In Metabolic Acidosis

• Anion gap:
[Na+] - ([Cl-] + [HCO3-]) = 8-16 mmol/L
Anion gap is another common
diagnostic calculation. It is used to
help differentiate between causes
• If > 18, there are unmeasured anions, such as:
of metabolic acidosis. It should be
– lactate
emphasized that ECF is an
– ketones
– salicylate
– ethanol
– ethylene glycol (anti-freeze) 14
electro-neutral solution in which the total number of anions and cations must be equal, such
that there is no actual anion gap in plasma! The calculation assesses the difference between
unmeasured cations (other than Na+) and unmeasured anions (other than Cl- and HCO3-). In
most cases of metabolic acidosis, the addition of a fixed acid results in lowering of HCO 3
through buffering and thus an increased anion gap, according to the calculation shown. In
effect the “anion gap” is occupied by the conjugate base anion of the fixed acid (e.g. lactate).
In most cases of metabolic acidosis anion gap is increased. If the cause of the metabolic
acidosis results in a rise in Cl- (for example diarrhea in which selective HCO3 loss occurs in
exchange for Cl), then metabolic acidosis results which is “hyperchloremic” and the anion
gap is found to be normal.

15
Diagnosis Of Acid Base Disturbances

Acid - Base Diagnosis

PaCO2 No Ventilatory HCO3- No Metabolic

No No
< 35 or >45? Component <21 or >28? Component

Yes Yes

PaCO2 Ventilatory HCO3- Metabolic

Yes Yes
< 35? Alkalosis >28? Alkalosis

No No

PaCO2 Ventilatory HCO3- Metabolic

Yes Yes
>45? Acidosis <21? Acidosis

pH
Acidemia Yes
<7.35?

No

pH
Normal pH Alkalemia Yes
>7.45?

No

source of diagram unknown

16
Define the acid base disturbance present in each of the following cases:

Case #2

• 36 year old heroin addict found unresponsive

with needle in arm
• P = 102, BP = 110/80, f = 5, T = 35.2 C
• ABG: PaO2 = 70, PaCO2 = 80, pH = 7.00, HCO3-
= 23, BD = -2

Case #3

• 16 year old with closed head injury after a

fall from 15 feet
• P = 132, BP = 115/90, f = 32, T = 37.2 C
• ABG: PaO2 = 110, PaCO2 = 26, pH = 7.52,
HCO3- = 22, BD = -1

Case #4

• 22 year old diabetic found unresponsive

• P = 102, BP = 110/80, f = 20, T = 36.2 C
• ABG PaO2 = 90, PaCO2 = 36, pH = 7.12,
HCO3- = 8, BD = -20

17
 Case #5

• 6 week old infant is lethargic with history of

vomiting increasing for 1 week
• P = 122, BP = 85/60, f = 24, T = 37.2 C
• ABG PaO2 = 90, PaCO2 = 44, pH = 7.62,
HCO3- = 36, BE = +12

Mixed Acid-Base Disorders and Compensation

The most common clinical presentation is to see more than one acid base disorder present
simultaneously. This is most often two opposing disorders in which a primary disorder is
being physiologically compensated to bring pH towards normal, but producing a secondary
acid base disturbance in the process. This situation is expected since pH is a controlled
variable subject to negative feedback.

Sometimes the terms “simple” and “compound” acid base disturbances are used, to
differentiate between a mixed acid base disorder in which there is “simple” compensation
and the situation where there is two independent pathologies producing effectively two
primary disorders. This terminology is not used clinically – KEEP IT SIMPLE – describe
the pH deviation (acidemia/alkalemia), describe any PCO2 deviation (respiratory
acidosis/alkalosis) and describe any HCO3/Base Excess disturbance (metabolic
acidosis/alkalosis). In many clinical situations, the concept of physiologic compensation
becomes redundant because of interventions made, such as IV infusions etc.

Consider the following clinical cases and describe the acid base disturbances present:

Case #6

• 63 year old with history of COPD due to

tobacco abuse
• P = 92, BP = 135/90, f = 26, T = 37.0 C
• ABG PaO2 = 65, PaCO2 = 55, pH = 7.34,
HCO3- = 31, BE = +9

Acid-base status?
Primary disorder?
Secondary disorder?
Compensation?

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 Case #7

• 39 year old with history of chronic renal

insufficiency due to hypertension
• P = 82, BP = 148/95, f = 20, T = 36.1 C
• ABG PaO2 = 88, PaCO2 = 30, pH = 7.33,
HCO3- = 14, BD = -11
Acid-base status?
Primary disorder?
Secondary disorder?
Compensation?

Case #1 Review

• 26 YO male involve in MVC

• Hypotensive and tachycardia at crash scene
• Altered mental status and multiple severe
injuries
• pH = 7.38; PaCO2 = 30 mm Hg; HCO3- = 18
mEq/L, BD = -8 mEq/L
Acid-base status?
Primary disorder?
Secondary disorder?
Compensation?

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