Acid-Base Balance

6 min read Updated Mar 26, 2026

Blood pH must stay between 7.35 and 7.45. A pH below 7.35 is acidosis; above 7.45 is alkalosis. Either extreme can be fatal. Two organ systems share the job of maintaining this narrow range: the lungs handle the fast response (seconds to minutes), and the kidneys handle the slow but powerful response (hours to days).

The MCAT tests acid-base physiology frequently and expects you to identify the disorder, determine the cause, and predict the compensation.

Acid-base nomogram plotting arterial pH vs pCO2 vs HCO3-, with labeled regions for metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis — Acid-base nomogram showing all four disorders. **Focus on:** identify the primary disorder from pH (acidosis < 7.35, alkalosis > 7.45), then determine if it's respiratory (CO2 abnormal) or metabolic (HCO3- abnormal). The body compensates by adjusting the other system. *Credit: Wikimedia Commons, Public Domain*

The Bicarbonate Buffer System

The body’s most important extracellular buffer is the bicarbonate system. The chemistry behind this buffer (Henderson-Hasselbalch equation) is covered in general chemistry - here we focus on how the body regulates it:

How the Kidneys Regulate pH

The kidneys have three mechanisms for acid-base regulation:

1. Bicarbonate reabsorption (PCT)

The PCT reabsorbs ~80-90% of filtered HCO3-
This is not direct reabsorption - HCO3- cannot cross the apical membrane
Instead: H+ is secreted into the lumen (via Na+/H+ exchangers), combines with filtered HCO3- to form CO2 + H2O (catalyzed by carbonic anhydrase on the brush border)
CO2 diffuses into the PCT cell, is reconverted to HCO3- (intracellular carbonic anhydrase), and HCO3- exits on the basolateral side into the blood
Net effect: each H+ secreted “reclaims” one HCO3-

2. H+ secretion (collecting duct)

Type A intercalated cells actively secrete H+ via H+ ATPase and H+/K+ ATPase
This generates NEW bicarbonate (not just reclaiming filtered HCO3-)
Each H+ secreted generates one new HCO3- that enters the blood
This is the kidney’s mechanism for correcting acidosis

3. Ammonium (NH4+) excretion

The PCT produces NH3 (ammonia) from glutamine
NH3 diffuses into the tubular lumen and combines with H+ to form NH4+ (ammonium)
NH4+ is trapped in the lumen (charged, cannot diffuse back) and excreted
This allows the kidney to excrete large amounts of H+ without dropping urine pH below ~4.5 (NH3 acts as a urinary buffer)

The Four Acid-Base Disorders

Disorder	Primary Problem	pH	Primary Change	Compensation
Metabolic acidosis	Excess H+ or loss of HCO3-	< 7.35	HCO3- low	Lungs hyperventilate (blow off CO2)
Metabolic alkalosis	Loss of H+ or excess HCO3-	> 7.45	HCO3- high	Lungs hypoventilate (retain CO2)
Respiratory acidosis	CO2 retention (hypoventilation)	< 7.35	CO2 high	Kidneys retain HCO3-, excrete H+
Respiratory alkalosis	CO2 loss (hyperventilation)	> 7.45	CO2 low	Kidneys excrete HCO3-, retain H+

How to Read an Arterial Blood Gas (ABG)

The MCAT may give you ABG values and ask you to identify the disorder:

Step 1: Look at pH. Is it acidotic (< 7.35) or alkalotic (> 7.45)?

Step 2: Determine the primary cause.

If CO2 is abnormal and matches the pH direction, it is respiratory
If HCO3- is abnormal and matches the pH direction, it is metabolic

Step 3: Check for compensation.

Is the other value changing in the expected compensatory direction?

Normal values:

pH: 7.35-7.45
pCO2: 35-45 mmHg
HCO3-: 22-26 mEq/L

Example: pH 7.30, pCO2 55 mmHg, HCO3- 28 mEq/L

pH is low (acidosis)
CO2 is high (respiratory cause - hypoventilation)
HCO3- is slightly elevated (renal compensation - kidneys retaining bicarbonate)
Diagnosis: respiratory acidosis with partial renal compensation

Common Causes of Each Disorder

Metabolic acidosis:

Diabetic ketoacidosis (excess ketone production)
Lactic acidosis (anaerobic metabolism)
Renal failure (cannot excrete H+ or regenerate HCO3-)
Severe diarrhea (loss of HCO3- in stool)

Metabolic alkalosis:

Prolonged vomiting (loss of HCl from stomach)
Excessive antacid use
Hyperaldosteronism (excess H+ secretion in collecting duct)

Respiratory acidosis:

COPD, pneumonia, or any cause of hypoventilation
Opioid overdose (suppresses respiratory drive)

Respiratory alkalosis:

Hyperventilation (anxiety, pain, high altitude)

A patient has pH 7.50, pCO2 48 mmHg, HCO3- 36 mEq/L. Identify the primary disorder and the compensation.

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Primary disorder: metabolic alkalosis (pH is high, HCO3- is high - the bicarbonate excess is driving the alkalosis). Compensation: respiratory (CO2 is elevated because the lungs are hypoventilating to retain CO2 and lower pH). The compensation is partial because pH has not returned to normal range. A common cause would be prolonged vomiting (loss of gastric HCl).

Why can't the lungs fully compensate for a metabolic acid-base disorder?

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Respiratory compensation is self-limiting. In metabolic acidosis, the lungs hyperventilate to blow off CO2. But excessive hyperventilation reduces CO2 so much that the low CO2 itself begins to inhibit respiratory drive (the body will not voluntarily suffocate). Similarly, in metabolic alkalosis, hypoventilation raises CO2, but hypoxia eventually forces breathing to resume. Only the kidneys can fully correct the primary problem by adjusting HCO3- directly.