Blood gas interpretation, acid-base and the Henderson-Hasselbalch equation

Overview and Importance

Precise regulation of blood pH is essential for normal cellular enzyme function, protein structure, oxygen delivery, and cardiac conductivity. The normal arterial blood pH is 7.35-7.45, corresponding to a hydrogen ion concentration $[\text{H}^+]$ of approximately 35-45 nmol/L. Values outside the range of pH 6.8-7.8 are generally incompatible with life.

The carbonic acid-bicarbonate buffer system is the central framework for understanding acid-base regulation, and three major systems work in concert to maintain pH homeostasis:

1. Chemical buffers (immediate, within seconds)
2. Respiratory compensation (rapid, minutes to hours)
3. Renal compensation (slower, hours to days, the only true corrective mechanism)

The Henderson-Hasselbalch Equation

The relationship between pH, $\text{PCO}_2$, and bicarbonate is described by the Henderson-Hasselbalch equation:

$$\text{pH} = \text{pK}_a + \log \frac{[\text{HCO}_3^-]}{[\text{dissolved CO}_2]}$$

Where dissolved $\text{CO}_2 = 0.0225 \times \text{PCO}_2$ (in mmHg), and $\text{pK}_a = 6.1$ for the carbonic acid system.

The key equilibrium reaction is:

$$\text{CO}_2 + \text{H}_2\text{O} \rightleftharpoons \text{H}_2\text{CO}_3 \rightleftharpoons \text{H}^+ + \text{HCO}_3^-$$

This equilibrium is catalysed by carbonic anhydrase in red blood cells, renal tubular cells, and other tissues. Perturbation of either $\text{PCO}_2$ (respiratory component) or $[\text{HCO}_3^-]$ (metabolic component) will shift pH accordingly.

Normal Values

Classification of Acid-Base Disturbances

Disturbances are classified by their origin and direction:

Respiratory Acidosis and Alkalosis

Respiratory Acidosis

Respiratory acidosis results from any process that causes retention of CO₂, elevating $\text{PCO}_2$ above 45 mmHg. The increased $\text{CO}_2$ drives the carbonic acid equilibrium to the right, increasing $[\text{H}^+]$ and lowering pH.

Common causes: hypoventilation, airway obstruction, respiratory muscle weakness, CNS depression (e.g. opioid overdose), severe lung disease.

Respiratory Alkalosis

Any short-term lowering of $\text{PCO}_2$ below 35 mmHg (as occurs with hyperventilation) results in respiratory alkalosis. Decreased $\text{CO}_2$ shifts the carbonic acid-bicarbonate equilibrium to effectively lower $[\text{H}^+]$ and raise pH.

Common causes: anxiety, pain, mechanical overventilation, altitude, pregnancy, hepatic failure.

Metabolic Acidosis and Alkalosis

Metabolic Acidosis

Metabolic (non-respiratory) acidosis occurs when strong acids are added to the blood by non-respiratory mechanisms. For example, in an aspirin overdose, acids in the blood rapidly increase. The $\text{H}_2\text{CO}_3$ formed is converted to $\text{H}_2\text{O}$ and $\text{CO}_2$, which is excreted via the lungs.

Key feature: In uncompensated metabolic acidosis, pH changes occur along a $\text{PCO}_2$ isobar line, unlike respiratory acidosis, there is no primary change in $\text{PCO}_2$.

Common causes: diabetic ketoacidosis, lactic acidosis, renal failure, ingestion of acids, diarrhoea (loss of $\text{HCO}_3^-$).

Metabolic Alkalosis

Metabolic alkalosis results when the free $[\text{H}^+]$ level falls due to:

• Addition of alkali to the blood, or
• More commonly, removal of large amounts of acid (e.g. vomiting with loss of gastric HCl)

In uncompensated metabolic alkalosis, pH rises along the $\text{PCO}_2$ isobar line.

Common causes: vomiting, nasogastric suction, diuretic use, exogenous bicarbonate administration, hyperaldosteronism.

Compensatory Mechanisms

Uncompensated acidosis and alkalosis are seldom seen in clinical practice because compensatory systems activate rapidly. The two main systems are respiratory compensation and renal compensation.

1. Respiratory Compensation (Fast, Minutes to Hours)

The respiratory system compensates for metabolic disturbances by altering alveolar ventilation, directly changing $\text{PCO}_2$ and thus blood pH.

Mechanism: Peripheral and central chemoreceptors detect changes in $[\text{H}^+]$ and $\text{PCO}_2$, sending signals to the respiratory centre in the medulla to adjust minute ventilation.

Important point: Because respiratory compensation begins almost simultaneously with the onset of metabolic acidosis, the large two-step pH swings depicted on theoretical diagrams overstate what occurs in practice. The compensatory response is invoked immediately, blunting the magnitude of pH change.

Limitation: Respiratory compensation cannot fully correct metabolic disturbances. It returns pH towards, but not completely to, normal. Complete restoration requires renal compensation.

2. Renal Compensation (Slow, Hours to Days)

Renal mechanisms are invoked for complete compensation from both respiratory and metabolic disturbances. The kidney is the only system capable of generating new $\text{HCO}_3^-$ and excreting fixed (non-volatile) acids.

Renal Response to Acidosis

Renal tubule cells contain active carbonic anhydrase and can produce $\text{H}^+$ and $\text{HCO}_3^-$ from $\text{CO}_2$.

In response to acidosis:

• Tubular cells secrete $\text{H}^+$ into the tubular fluid in exchange for $\text{Na}^+$
• $\text{HCO}_3^-$ is actively reabsorbed into the peritubular capillary
• Net result: For each $\text{H}^+$ secreted, one $\text{Na}^+$ and one $\text{HCO}_3^-$ are added to the blood
• Fixed acids are actively secreted

This mechanism is responsible for the graphical shift from acute to chronic respiratory acidosis, as the kidney progressively raises plasma $[\text{HCO}_3^-]$ to buffer the elevated $\text{PCO}_2$.

Renal Response to Alkalosis

In response to alkalosis:

• The kidney decreases $\text{H}^+$ secretion
• Depresses $\text{HCO}_3^-$ reabsorption, allowing more bicarbonate to be excreted in the urine

This accounts for the shift from acute to chronic respiratory alkalosis, where renal $\text{HCO}_3^-$ wasting lowers plasma bicarbonate and returns pH towards normal.

Acute vs Chronic Disturbances

The distinction between acute (uncompensated) and chronic (compensated) disturbances is clinically important:

Summary of Compensation Rules

The expected degree of compensation can be estimated using standard formulae (for examination purposes):

Davenport Diagram

The Davenport (or Siggaard-Andersen) diagram plots $[\text{HCO}_3^-]$ against pH with $\text{PCO}_2$ isobars, allowing graphical representation of all four primary disturbances and their compensations:

• Metabolic disturbances cause movement along a $\text{PCO}_2$ isobar (horizontal trajectory on the pH/$\text{HCO}_3^-$ plot)
• Respiratory disturbances cause movement across isobars
• Compensation moves the operating point back towards the normal point

Clinical Relevance

Anaesthetic Implications

1. Respiratory control during anaesthesia

• General anaesthesia and sedation depress respiratory drive, causing hypoventilation and respiratory acidosis
• Mechanical ventilation allows direct manipulation of $\text{PCO}_2$; inappropriate settings can cause either respiratory acidosis (underventilation) or iatrogenic respiratory alkalosis (overventilation)
• Respiratory alkalosis from excessive mechanical ventilation can shift the oxyhaemoglobin dissociation curve to the left , impairing $\text{O}_2$ delivery to tissues

2. Permissive hypercapnia

• In lung-protective ventilation strategies (e.g. ARDS), deliberate acceptance of elevated $\text{PCO}_2$ (respiratory acidosis) may be tolerated to avoid ventilator-induced lung injury

3. Opioid-induced respiratory depression

• All opioids depress central respiratory drive → hypoventilation → $\uparrow \text{PCO}_2$ → respiratory acidosis; this is a major risk in the perioperative period and PACU

4. Hyperventilation and cerebral blood flow

• $\text{CO}_2$ is a potent cerebral vasodilator; deliberate hyperventilation causing hypocapnia (respiratory alkalosis) is used to reduce intracranial pressure acutely in neurological emergencies. However, this may compromise cerebral perfusion if prolonged

5. Metabolic acidosis in the perioperative setting

• Large-volume saline infusion can cause hyperchloraemic metabolic acidosis
• Haemorrhagic shock produces lactic acidosis from anaerobic metabolism
• Both require recognition and appropriate management

6. Metabolic alkalosis

• Prolonged nasogastric suction, high-dose loop diuretics, or vomiting (common preoperatively) can produce metabolic alkalosis
• This blunts the respiratory drive, causing hypoventilation and making weaning from mechanical ventilation more difficult

7. Renal considerations

• ACE inhibitors, ARBs, and NSAIDs impair renal tubular function and can limit renal compensation; important in the perioperative setting
• Patients with chronic kidney disease have reduced capacity for renal compensation of acid-base disturbances

8. Carbonic anhydrase inhibitors

• Acetazolamide inhibits carbonic anhydrase → reduces renal $\text{HCO}_3^-$ reabsorption → metabolic acidosis; used therapeutically for altitude sickness and as an adjunct in some situations requiring controlled acidosis

9. Interpretation of arterial blood gases

• A systematic approach to ABG interpretation is essential: assess pH → identify primary disturbance → assess compensation (is it appropriate?) → consider mixed disturbances
• Recognise that compensation never fully corrects pH back to 7.40 (except in chronic respiratory alkalosis, where near-complete renal compensation can sometimes normalise pH)

10. Temperature correction

• Hypothermia reduces metabolic rate and $\text{CO}_2$ production; blood gases may be interpreted using alpha-stat (uncorrected for temperature) or pH-stat (corrected to patient temperature) strategies, particularly relevant in cardiopulmonary bypass

Sources

• ANZCA clinical guidelines
• ANZCA Professional Documents (PS series)