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Acid–Base Balance
\( \text{CO}_2 \) / Bicarbonate

Explore how your body maintains a stable blood pH through the carbonic acid–bicarbonate buffer system, the role of \( \text{CO}_2 \), and the organs that keep everything in balance.

Anatomy & Physiology

Why Blood pH Matters

Your blood must stay within a narrow pH range of 7.35 – 7.45. Even small deviations can denature enzymes, disrupt nerve signaling, and impair oxygen delivery. The body uses buffer systems, the lungs, and the kidneys to defend this range constantly.

Below 7.35
Acidosis: confusion, fatigue, coma if severe
7.35 – 7.45
Normal range: enzymes and proteins function optimally
Above 7.45
Alkalosis: muscle twitching, numbness, seizures

Key Terms to Know

1
pH: A logarithmic scale measuring hydrogen ion concentration: \( \text{pH} = -\log[\text{H}^+] \)
2
Buffer: A chemical system that resists changes in pH by absorbing or releasing \( \text{H}^+ \) ions
3
Carbonic acid \( (\text{H}_2\text{CO}_3) \): A weak acid formed when \( \text{CO}_2 \) dissolves in blood plasma
4
Bicarbonate \( (\text{HCO}_3^-) \): The conjugate base that neutralizes excess \( \text{H}^+ \) in the blood
5
Carbonic anhydrase: The enzyme in red blood cells that catalyzes the \( \text{CO}_2 + \text{H}_2\text{O} \) reaction

The Bicarbonate Buffer System

The most important buffer in blood plasma is the carbonic acid–bicarbonate system. It accounts for roughly 75% of all chemical buffering in the body.

\( \text{CO}_2 + \text{H}_2\text{O} \)
 reactants carbonic anhydrase
\( \text{H}_2\text{CO}_3 \)
 carbonic acid
\( \text{HCO}_3^- + \text{H}^+ \)
 bicarbonate + hydrogen Reversible equilibrium: shifts left or right to maintain pH

The Core Equation

The single most important equation in acid–base physiology:

Left side
\( \text{CO}_2 \) is produced by cellular metabolism and carried to the lungs
Middle
\( \text{H}_2\text{CO}_3 \) is unstable and quickly dissociates
Right side
\( \text{HCO}_3^- \) buffers acid; \( \text{H}^+ \) determines pH

The Henderson–Hasselbalch Equation

This equation links three measurable clinical values: pH, bicarbonate concentration, and partial pressure of \( \text{CO}_2 \). The normal ratio of \( \frac{[\text{HCO}_3^-]}{[\text{H}_2\text{CO}_3]} \) is approximately 20 : 1.

\( [\text{HCO}_3^-] \)
Normal: 22 – 26 mEq/L (regulated by kidneys)
\( P_{\text{CO}_2} \)
Normal: 35 – 45 mmHg (regulated by lungs)

Respiratory vs Metabolic

Acid–base imbalances are classified by their origin. The lungs control the \( \text{CO}_2 \) side (respiratory), while the kidneys control the \( \text{HCO}_3^- \) side (metabolic).

Respiratory Metabolic
Primary change \( P_{\text{CO}_2} \) \( [\text{HCO}_3^-] \)
Organ involved Lungs Kidneys
Speed of response Seconds to minutes Hours to days
Acidosis cause \( \uparrow \text{CO}_2 \) (hypoventilation) \( \downarrow \text{HCO}_3^- \) or \( \uparrow \text{H}^+ \)
Alkalosis cause \( \downarrow \text{CO}_2 \) (hyperventilation) \( \uparrow \text{HCO}_3^- \) or \( \downarrow \text{H}^+ \)

How the Body Compensates

When one system causes a pH shift, the other system compensates to restore the 20:1 ratio. Compensation does not fully correct pH; it minimizes the deviation.

Lungs
Adjust \( \text{CO}_2 \) (fast)
 Kidneys
Adjust \( \text{HCO}_3^- \) (slow)
 pH 7.35–7.45 respiratory compensation renal compensation Respiratory issues → renal compensation (slow) Metabolic issues → respiratory compensation (fast)

How to Interpret Blood Gases

1
Check the pH: Is it < 7.35 (acidosis) or > 7.45 (alkalosis)?
2
Check \( P_{\text{CO}_2} \): Is it > 45 mmHg (respiratory acidosis) or < 35 mmHg (respiratory alkalosis)?
3
Check \( [\text{HCO}_3^-] \): Is it < 22 mEq/L (metabolic acidosis) or > 26 mEq/L (metabolic alkalosis)?
4
Match the culprit: Which value (\( P_{\text{CO}_2} \) or \( \text{HCO}_3^- \)) explains the pH shift?
5
Look for compensation: Is the other value moving in the opposite direction to restore pH?

Example 1: Respiratory Acidosis

1
pH = 7.30 → below 7.35 → this is acidosis
2
\( P_{\text{CO}_2} \) = 55 mmHg → above 45 → \( \text{CO}_2 \) is elevated → respiratory cause
3
\( \text{HCO}_3^- \) = 26 mEq/L → normal/slightly high → kidneys beginning to compensate

Example 2: Metabolic Acidosis

1
pH = 7.25 → acidosis
2
\( \text{HCO}_3^- \) = 12 mEq/L → far below 22 → metabolic cause (ketoacids consumed bicarbonate)
3
\( P_{\text{CO}_2} \) = 25 mmHg → below 35 → lungs compensating by blowing off \( \text{CO}_2 \) (Kussmaul breathing)

Example 3: Respiratory Alkalosis

1
pH = 7.52 → above 7.45 → alkalosis
2
\( P_{\text{CO}_2} \) = 28 mmHg → below 35 → excessive \( \text{CO}_2 \) exhalation → respiratory cause
3
\( \text{HCO}_3^- \) = 23 mEq/L → still normal → no renal compensation yet (acute event)

Equilibrium Shifts in Action

\( \text{CO}_2 + \text{H}_2\text{O} \rightleftharpoons \text{H}_2\text{CO}_3 \rightleftharpoons \text{HCO}_3^- + \text{H}^+ \)
 normal equilibrium at pH 7.40
\( \uparrow \text{CO}_2 \)
 Shift RIGHT
\( \uparrow \text{H}^+ \rightarrow \downarrow \text{pH} \)
\( \downarrow \text{CO}_2 \)
 Shift LEFT
\( \downarrow \text{H}^+ \rightarrow \uparrow \text{pH} \)
\( \uparrow \text{H}^+ \) (acid)
 Shift LEFT
\( \text{HCO}_3^- \) buffers \( \text{H}^+ \)
\( \downarrow \text{H}^+ \) (base)
 Shift RIGHT
\( \text{H}_2\text{CO}_3 \) releases \( \text{H}^+ \)

The Lungs: Fast Responders

The respiratory system adjusts \( \text{CO}_2 \) levels within seconds to minutes. Chemoreceptors in the brainstem and aortic/carotid bodies detect pH changes and modify ventilation rate.

Acidosis detected
Breathing rate increases → exhale more \( \text{CO}_2 \) → shift equilibrium left → \( \text{H}^+ \) decreases → pH rises
Alkalosis detected
Breathing rate decreases → retain \( \text{CO}_2 \) → shift equilibrium right → \( \text{H}^+ \) increases → pH falls

The Kidneys: Powerful but Slow

Renal compensation takes hours to days but can fully correct pH. The kidneys adjust by excreting or retaining \( \text{H}^+ \) and \( \text{HCO}_3^- \).

1
In acidosis: kidneys excrete \( \text{H}^+ \) into urine and reabsorb \( \text{HCO}_3^- \) back into blood
2
In alkalosis: kidneys excrete \( \text{HCO}_3^- \) into urine and retain \( \text{H}^+ \)
3
New bicarbonate: kidneys can also generate new \( \text{HCO}_3^- \) from glutamine metabolism in tubular cells

Common Mistakes

✕ Confusing cause and compensation
If \( P_{\text{CO}_2} \) is low in metabolic acidosis, that is compensation, not a second disorder. Always start with pH to identify the primary problem.
✕ Forgetting the 20:1 ratio
pH depends on the ratio of \( \text{HCO}_3^- \) to \( \text{CO}_2 \), not their absolute values. Both can change and pH can remain normal if the ratio holds.
✕ Mixing up acid and base directions
More \( \text{CO}_2 \) = more acid = lower pH. More \( \text{HCO}_3^- \) = more base = higher pH. Students often reverse this.

Summary of Imbalances

Condition pH \( P_{\text{CO}_2} \) \( \text{HCO}_3^- \) Compensation
Respiratory Acidosis ↓ ↑ Normal → ↑ Kidneys retain \( \text{HCO}_3^- \)
Respiratory Alkalosis ↑ ↓ Normal → ↓ Kidneys excrete \( \text{HCO}_3^- \)
Metabolic Acidosis ↓ Normal → ↓ ↓ Lungs hyperventilate
Metabolic Alkalosis ↑ Normal → ↑ ↑ Lungs hypoventilate

Question 1 of 5

The enzyme carbonic anhydrase catalyzes which reaction?

Question 2 of 5

A patient has: pH = 7.48, \( P_{\text{CO}_2} \) = 30 mmHg, \( \text{HCO}_3^- \) = 23 mEq/L. What is the primary disorder?

Question 3 of 5

If blood \( \text{CO}_2 \) levels increase, what happens to \( [\text{H}^+] \) and pH?

Question 4 of 5

In the Henderson–Hasselbalch equation, what is the normal ratio of \( [\text{HCO}_3^-] \) to \( [\text{H}_2\text{CO}_3] \)?

Question 5 of 5

How do the kidneys compensate for respiratory acidosis?