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Respiratory Acidosis and Respiratory Alkalosis
RESPIRATORY ACIDOSIS
Definition & Primary Disturbance
Respiratory acidosis results from hypoventilation, causing CO₂ retention and a rise in PaCO₂ (hypercapnia). The increased PCO₂ is the primary disturbance, which by the Henderson-Hasselbalch equation drives pH down.
Arterial Blood Gas Profile:
| Parameter | Change |
|---|
| pH | ↓ (< 7.35) |
| PaCO₂ | ↑ (primary) |
| HCO₃⁻ | ↑ (compensatory) |
Pathophysiology
The sequence of events:
1. CO₂ Retention
Hypoventilation causes PCO₂ to rise. By mass action (CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃⁻), H⁺ increases (pH falls) and HCO₃⁻ rises proportionally.
2. Buffering
Buffering of excess CO₂ occurs exclusively in the ICF, especially in red blood cells. CO₂ diffuses into cells, is converted to H⁺ and HCO₃⁻, and H⁺ is buffered by intracellular proteins (hemoglobin) and organic phosphates.
3. No Respiratory Compensation
There is no respiratory compensation for respiratory acidosis - the lung is the cause of the disorder.
4. Renal Compensation
- Increased H⁺ excretion as titratable acid and NH₄⁺
- Increased synthesis and reabsorption of new HCO₃⁻
- NH₄⁺ formation is accelerated over days
- Chronic respiratory acidosis may down-regulate the apical HCO₃⁻/Cl⁻ exchanger (pendrin) in the distal tubule
Compensatory Responses (Expected)
| Type | Formula | Onset |
|---|
| Acute | HCO₃⁻ rises ~1 mEq/L per 10 mmHg ↑ PaCO₂ | Minutes (cellular buffering) |
| Chronic | HCO₃⁻ rises ~4 mEq/L per 10 mmHg ↑ PaCO₂ | >24-48 hours (renal), complete by ~5 days |
Serum bicarbonate generally does not exceed 38 mEq/L even with maximum renal compensation.
Causes
| Category | Examples |
|---|
| CNS/Respiratory center depression | Opioids, barbiturates, anesthetics, alcohol, head trauma, intracranial tumors, sleep apnea (central), obesity-hypoventilation syndrome |
| Neuromuscular disorders | Guillain-Barré syndrome, polio, ALS, multiple sclerosis, myasthenia gravis, diaphragm paralysis |
| Airway obstruction | Aspiration, obstructive sleep apnea, laryngospasm |
| Disorders of gas exchange | COPD (most common cause), ARDS, pneumonia, pulmonary edema, interstitial lung disease, large pleural effusions, pulmonary embolism |
| Mechanical ventilation | Inadequate settings, barotrauma, ET tube displacement, permissive hypercapnia |
| Chest wall disorders | Extensive rib fractures, flail chest, kyphoscoliosis |
COPD is the most frequent cause, primarily because of reduced alveolar ventilation from mechanical disadvantage and respiratory muscle weakness. - Murray & Nadel's Textbook of Respiratory Medicine
Clinical Features
Manifestations vary by severity, acuity, and the presence of hypoxemia:
Acute (rapid PCO₂ rise):
- Anxiety, dyspnea, confusion
- Psychosis, hallucinations
- Progression to coma
Chronic (gradual hypercapnia):
- Sleep disturbances, daytime somnolence
- Loss of memory, personality changes
- Impaired coordination
Neurological signs (from cerebral vasodilation by CO₂):
- Headaches (CO₂ is a potent cerebral vasodilator)
- Papilledema (mimics raised ICP)
- Asterixis, tremor, myoclonic jerks
- Abnormal reflexes, focal muscle weakness
COPD-specific note: Central chemoreceptors can be suppressed by chronic hypercapnia (because renal HCO₃⁻ generation raises CSF pH, blunting the pH signal). These patients rely on carotid body (hypoxic) drive - hence giving high-flow O₂ can suppress ventilation, worsen hypercapnia, and lead to narcosis. - Murray & Nadel's
Treatment
- Treat the underlying cause - improve ventilation
- Assisted ventilation (NIV or intubation/mechanical ventilation) when severe
- Permissive hypercapnia: In mechanically ventilated patients with ARDS, low tidal volumes reduce barotrauma even at the cost of mild hypercapnia; pH is monitored closely
- Bicarbonate infusion: Only considered in mixed respiratory + metabolic acidosis; goal is NOT to normalize pH but to partially correct acidemia
- Avoid supplemental O₂ excess in COPD (suppresses hypoxic drive)
RESPIRATORY ALKALOSIS
Definition & Primary Disturbance
Respiratory alkalosis results from hyperventilation, causing excessive loss of CO₂ and a fall in PaCO₂ (hypocapnia). The decreased PCO₂ is the primary disturbance, driving pH upward.
Arterial Blood Gas Profile:
| Parameter | Change |
|---|
| pH | ↑ (> 7.45) |
| PaCO₂ | ↓ (primary) |
| HCO₃⁻ | ↓ (compensatory) |
Pathophysiology
1. Loss of CO₂
Hyperventilation causes PCO₂ to fall. By mass action, H⁺ decreases (pH rises) and HCO₃⁻ also falls.
2. Buffering
Occurs in the ICF - H⁺ exits cells in exchange for K⁺ (or Na⁺), moving into the ECF to partially buffer the alkalosis. Within cells, the reverse reaction regenerates CO₂ from HCO₃⁻ and H⁺.
3. No Respiratory Compensation
The lung is the cause; there is no meaningful respiratory compensation.
4. Renal Compensation
- Decreased H⁺ excretion and decreased NH₄⁺ formation
- Reduced HCO₃⁻ reabsorption → HCO₃⁻ is excreted in urine
- Full renal compensation takes 2-3 days
Compensatory Responses (Expected)
| Type | Formula | Onset |
|---|
| Acute | HCO₃⁻ falls ~2 mEq/L per 10 mmHg ↓ PaCO₂ | Rapid (cellular buffering) |
| Chronic | HCO₃⁻ falls ~2.5 mEq/L per 10 mmHg ↓ PaCO₂ | 2-3 days (renal) |
Serum bicarbonate generally does not fall below 16 mEq/L in pure respiratory alkalosis (lower suggests concurrent metabolic acidosis). - Murray & Nadel's
Causes
| Category | Examples |
|---|
| Stimulation of medullary respiratory center | Anxiety/hysterical hyperventilation, gram-negative septicemia, salicylate (aspirin) poisoning, neurologic disorders (stroke, tumor), liver failure (hepatic encephalopathy), fever, pain |
| Hypoxemia (stimulates peripheral chemoreceptors) | High altitude, pneumonia, pulmonary embolism, severe anemia, CHF |
| Mechanical ventilation | Excessive tidal volume or rate settings |
| Pregnancy | Progesterone stimulates respiratory center (normal physiologic alkalosis) |
| Drugs | Salicylates (early), catecholamines, theophylline |
| Thyrotoxicosis | Increased metabolic rate with stimulation of breathing |
Note: Salicylate toxicity initially causes respiratory alkalosis (direct CNS stimulation of respiration), followed later by metabolic acidosis - giving a classic mixed picture.
Clinical Features
Symptoms result from hypocapnia-induced cerebral vasoconstriction and hypocalcemia from increased protein-bound Ca²⁺:
CNS effects (from cerebral vasoconstriction):
- Light-headedness, dizziness
- Confusion, syncope
Peripheral neuromuscular effects (from decreased free ionized Ca²⁺):
- Paresthesias (tingling and numbness of hands, feet, and perioral region)
- Carpopedal spasm
- Tetany
- Positive Chvostek's and Trousseau's signs
Cardiac effects:
- Increased cardiac excitability
- Can precipitate arrhythmias (alkalosis shifts K⁺ into cells, causing hypokalemia)
Mechanism of hypocalcemia in alkalosis: With decreased H⁺, more H⁺ dissociates from albumin → more Ca²⁺ binds albumin → free ionized Ca²⁺ falls → neuronal excitability increases.
Classic case (Costanzo Physiology): A 24-year-old anxious female hyperventilates before exams - ABG shows pH 7.56, PCO₂ 23 mmHg, HCO₃⁻ 20 mEq/L. Symptoms: light-headedness and tingling of hands and feet. Treatment: breathe into a paper bag (rebreathing CO₂ restores PCO₂ to normal).
Treatment
- Treat the underlying cause (most important)
- Anxiety/psychogenic hyperventilation: Rebreathing (paper bag), reassurance, anxiolytics
- Hypoxemia-driven: Supplemental oxygen (corrects the stimulus)
- Mechanical ventilation-induced: Reduce rate or tidal volume; add dead-space
- Sepsis-driven: Antimicrobials and source control
- Salicylate toxicity: Urinary alkalinization and dialysis if severe
COMPARISON TABLE
| Feature | Respiratory Acidosis | Respiratory Alkalosis |
|---|
| Primary cause | Hypoventilation | Hyperventilation |
| Primary disturbance | ↑ PaCO₂ | ↓ PaCO₂ |
| pH | < 7.35 | > 7.45 |
| HCO₃⁻ direction | ↑ (compensation) | ↓ (compensation) |
| Acute compensation | HCO₃⁻ +1 per 10 mmHg ↑ PCO₂ | HCO₃⁻ -2 per 10 mmHg ↓ PCO₂ |
| Chronic compensation | HCO₃⁻ +4 per 10 mmHg ↑ PCO₂ | HCO₃⁻ -2.5 per 10 mmHg ↓ PCO₂ |
| Compensation organ | Kidney | Kidney |
| CNS symptoms | Somnolence, narcosis, asterixis | Light-headedness, tetany, paresthesias |
| Commonest cause | COPD | Anxiety/hyperventilation, sepsis |
| Max HCO₃⁻ | ~38 mEq/L | Rarely <16 mEq/L |
KEY FORMULAS FOR ABG INTERPRETATION
Respiratory Acidosis:
- Acute: Expected HCO₃⁻ = 24 + [0.1 × (PCO₂ - 40)]
- Chronic: Expected HCO₃⁻ = 24 + [0.4 × (PCO₂ - 40)]
Respiratory Alkalosis:
- Acute: Expected HCO₃⁻ = 24 - [0.2 × (40 - PCO₂)]
- Chronic: Expected HCO₃⁻ = 24 - [0.25 × (40 - PCO₂)]
If measured HCO₃⁻ is higher than expected → superimposed metabolic alkalosis
If measured HCO₃⁻ is lower than expected → superimposed metabolic acidosis
Sources: - Costanzo Physiology, 7th Ed. - Brenner and Rector's The Kidney, 2-Vol. Set - Murray & Nadel's Textbook of Respiratory Medicine, 2-Vol.
