Introduction

Homeothermic mammals, including humans, normally maintain both intracellular

and extracellular pH within a rather narrow range of values, with the normal values being
approximately 6.9 and 7.4, respectively. Because intracellular pH is difficult to measure,
most physiological and clinical evaluations focus on extracellular pH, which is measured
in samples of arterial or venous blood. Among the different body compartments,
including vascular and extravascular, as well as intra- and extracellular, blood is easily
accessible and the pH values in blood are presumed to reflect whole body pH, including
the intracellular compartment. Values of blood extracellular fluid pH above 7.7 and below
6.9 in humans can result in morbidity and mortality. A clear understanding of the
importance of pH and how to interpret clinically available acid-base data is of utmost
importance to the physician.
‘Respiratory regulation’ refers to changes in pH due to pCO2 changes from
alterations in ventilation. This change in ventilation can occur rapidly with significant
effects on pH. Carbon dioxide is lipid soluble and crosses cell membranes rapidly, so
changes in pCO2 result in rapid changes in [H+] in all body fluid compartments.
A quantitative appreciation of respiratory regulation requires knowledge of two
relationships which provide the connection between alveolar ventilation and pH via
pCO2. These 2 relationships are:

• First equation - relates alveolar ventilation (VA) and pCO2

• Second equation - relates pCO2 and pH.

First Equation: Alveolar ventilation - Arterial pCO2 Relationship

Relationship: Changes in alveolar ventilation are inversely related to changes in arterial

pCO2 (& directly proportional to total body CO2 production).

paCO2 is proportional to [VCO2 / VA]

where:

• paCO2 = Arterial partial pressure of CO2

• VCO2 = Carbon dioxide production by the body

• VA = Alveolar ventilation

Alternatively, this formula can be expressed as:

paCO2 = 0.863 x [ VCO2 / VA ]

(if VCO2 has units of mls/min at STP and VA has units of l/min at 37C and at
atmospheric pressure.)
Second Equation: Henderson-Hasselbalch Equation

Relationship: These changes in arterial pCO2 cause changes in pH (as defined in the
Henderson-Hasselbalch equation):
pH = pKa + log { [HCO3] / (0.03 x pCO2) }

or more simply: The Henderson equation:

[H+] = 24 x ( pCO2 / [HCO3] )

The key point is that these 2 equations can be used to calculate the effect on pH of
a given change in ventilation provided of course the other variables in the equations (eg
body's CO2 production) are known.
Control System
The control system for respiratory regulation of acid-base balance can be
considered using the model of a simple servo control system. The components of such a
simple model are a controlled variable which is monitored by a sensor, a central
integrator which interprets the information from the sensor and an effector mechanism
which can alter the controlled variable. The servo control means that the system works in
such a way as to attempt to keep the controlled variable constant or at a particular set-
point. This means that a negative feedback system is in operation and the elements of the
system are connected in a loop.
Control systems in the body are generally much more complex than this simple
model but it is still a very useful exercise to at first attempt such an analysis.
Control System
for Respiratory
Regulation of
Acid-base
Balance

Control Physiological or Comment

Element Anatomical Correlate
Controlled Arterial pCO2 A change in arterial pCO2 alters arterial
variable pH (as calculated by use of the
Henderson-Hasselbalch Equation).
Sensors Central and peripheral Both respond to changes in arterial
chemoreceptors pCO2 (as well as some other factors)
 Central The respiratory center
integrator in the medulla
Effectors The respiratory muscles An increase in minute ventilation
increases alveolar ventilation and thus
decreases arterial pCO2 (the controlled
variable) as calculated from 'Equation
1'(discussed previously). The net result
is of negative feedback which tends to
restore the pCO2 to the 'setpoint'

'Acid-base pHysiology' by Kerry Brandis