Principles of Acid-Base Physiology

Explain the principles underlying acid-base chemistry

There have been several different theories of acid-base chemistry. The one most relevant for the primary exam is the Brønsted–Lowry definition, which defines:

• An acid as a proton donor
• A base as a proton acceptor

pH

• Stands for the power of hydrogen
• Is a measure of hydrogen ion activity in a solution
  • Activity can be approximated by concentration
  • Therefore, pH can be expressed as a function of hydrogen ion concentration: $pH = -log_{10}[H^+]$
    Using pH rather than concentration makes it easier to compare different solutions.

pKa

• Strong acids (and bases) dissociate completely in solution
• Weak acids (and bases) only partially dissociate
  They have a dissociated state (A-) and an undissociated state (HA)
• The ratio of concentrations on each side can be used to calculate the acid dissociation constant, Ka
  $Ka = {[A^-] \times [H^+] \over [HA]}$
  This equation describes the strength of an acid by indicating how readily the acid gives up its hydrogen.
• Similar to pH, this value is often log transformed to pKa produce an index, which allows easy comparison of different substances:
  $pKa = -log_{10}Ka$
• pKa has several useful properties:
  • An acid of base will be 50% ionised when the pH of its solution equals its pKa
  • Acids are more ionised above their pKa
  • Bases are more ionised below their pKa
  • An increase in pH of 1 above the pKa will result in that substance being either 90% (for an acid) or 10 % (for a base) ionised

Systemic Effects of Acid-Base Disorders

pH disturbance affects many organ systems:

• Respiratory
  • Increased $\dot{V}_A$
    Peripheral and central chemoreceptors increase ventilation in response to a fall in pH.
  • Oxyhaemoglobin-Dissociation Curve
    Right-shifted by a fall in pH.
  • Bronchoconstriction
    Hypercapnea causes parasympathetically-mediated bronchoconstriction.
• Cardiovascular
  • Inotropy
    Inotropy falls in acidosis due to a direct myocardial depressant effect. May be offset by increased SNS tone in low-grade acidosis. Alkalosis may increase inotropy by increasing responsiveness to circulating catecholamines.
  • Decreased response to catecholamines
    When pH < 7.2.
  • Arrhythmias
    Secondary to altered SNS tone and electrolytes.
  • Vasodilation
    Directly due to hypercapnea.
• CNS
  H⁺ ions cannot cross the BBB, however CO₂ can.
• Fluid and Electrolyte
  • Plasma K⁺ increases by 0.6mmol.L^-1 for every 0.1 unit fall in pH
    This is due to impairment of the Na⁺/K⁺-ATPase
  • H⁺ ions bind to the same site on albumin as calcium, so ionised calcium will increase
• MSK
  • Bones
    Chronic metabolic acidosis consumes bone phosphate to buffer H⁺ ions, causing osteoporosis.
• Cellular
  • Enzyme function
    Denaturation and functional impairment.
  • Molecular ionisation
    Change in ionisation may change a molecules ability to cross cell membranes (e.g. reducing dose of thiopentone in acidosis), or affect their function
  • Resting membrane potential
    Change in ion permeability will alter RMP, and therefore how easy it is to generate an action potential.

Change with Temperature

pH is temperature dependent:

• pH increases by 0.015 for every 1°C fall in temperature
  Due to decreased ionic dissociation of water.
• Gas solubility almost always increases when temperature falls
  Dissolving is typically (not always) an exothermic reaction. As the kinetic energy content of a molecule falls, its ability to dissociate from solution decreases.
  • As CO₂ dissolves, PaCO₂ falls
• As blood gas machines operate at 37°C, a measurement error will occur if a patient is not close to 37°C
  • A hypothermic patient will have a higher pH and CO₂ than measured

There are two common methods for managing pH of significantly hypothermic patients (e.g., those on CPB): pH-stat and alpha-stat.

pH-stat

• CO₂ is added to the circuit so that pH and PaCO₂ are normal when corrected for temperature
• This theoretically improves oxygen delivery by preventing the left-shift in the oxyhaemoglobin dissociation curve
• The increased CO₂ also causes cerebral vasodilation, which:
  • Increases speed and uniformity of cerebral cooling
  • Increases risk of cerebral embolic events

alpha-stat

• pH and CO₂ values are maintained at 'normal for 37°C'
  • Measured values will be different, as:
    • pH will be increased
    • CO₂ will be decreased
• Cellular autoregulation is preserved
• Unlike pH-stat, this does not cause cerebral vasodilation

References

1. Chambers D, Huang C, Matthews G. Basic Physiology for Anaesthetists. Cambridge University Press. 2015.
2. ANZCA July/August 1999
3. Chemlab. Solubility. Florida State University.