Biochemical Mechanisms Linking Mouth Breathing, Airway Obstruction, and Nocturnal Enuresis

Dr Scott Wustenberg D.C, FACNEM, M.Sc. NutMed (Distinction), B.Sc. Chiro, B.Sc. Physiology/Biochemistry
Email: neo@advancerehab.com.au

ABSTRACT

Airway fragmentation—including mouth breathing, airway occlusion, apnoea, and hypopnea—initiates a series of biochemical, physiological, and neurological events that culminate in nocturnal enuresis (bedwetting). These mechanisms involve hormonal dysregulation, sympathetic overactivation, renal dysfunction, altered sleep architecture, detrusor instability, and metabolic disturbances. This paper outlines 10 interconnected pathways linking sleep-disordered breathing (SDB) to bedwetting, with emphasis on natriuretic peptides, antidiuretic hormone disruption, cortisol and catecholamines, RAAS activation, renal hypoxia, bladder physiology, arousal mechanisms, and respiratory alkalosis from mouth breathing.

1. Hormonal Pathway: Natriuretic Peptides (ANP/BNP)

Mechanism

Upper airway obstruction increases inspiratory effort against an occluded airway, generating severe negative intrathoracic pressure (–15 to –17 mmHg). This markedly increases venous return and stretches the atrial and ventricular walls, triggering release of:

• ANP (Atrial Natriuretic Peptide) from the atria
• BNP (Brain/B-type Natriuretic Peptide) from the ventricles

Effect on Kidneys

ANP/BNP:

• Increase sodium and water excretion
• Suppress RAAS
• Reduce ADH secretion
• Increase GFR
         Result → Nocturnal polyuria exceeding bladder capacity.

Effect on Blood Pressure

Although ANP/BNP are vasodilatory, this effect is overshadowed by sympathetic surges at the termination of apnoeic events.

Evidence

ANP and BNP levels correlate directly with apnoea severity. Elevated morning BNP is found in children with SDB and enuresis. These markers normalize following adenotonsillectomy, CPAP, or airway-expanding interventions (e.g., TOT release, orthodontics).

2. Hormonal Pathway: Antidiuretic Hormone (ADH/Vasopressin) Suppression

Mechanism

Normal sleep increases ADH to reduce nighttime urine volume. Sleep fragmentation from apnoea/hypopnea disrupts ADH circadian rhythm. Elevated ANP/BNP further suppress ADH release.

Effect on Kidneys

Reduced ADH →

• Impaired water reabsorption
• Dilute nocturnal urine
• Increased urine volume
         → Bladder overfilling

Effect on Blood Pressure

Reduced vasopressin minimally contributes to nocturnal blood pressure variance relative to sympathetic activation.

Evidence

Enuretic children with OSA exhibit absent or blunted nocturnal ADH peaks and show a “non-dipping” nocturnal blood pressure pattern.

3. Hormonal Pathway: Cortisol and Catecholamines (HPA Axis + Sympathoadrenal System)

Mechanism

Hypoxia and repetitive arousals activate:

• HPA axis → cortisol
• Sympathetic nervous system → adrenaline and noradrenaline

This is a survival-based response to airway obstruction.

Effect on Kidneys

Cortisol alters glucose handling, immune signaling, fluid balance, and bladder sensory pathways.

Catecholamines:

• Renal vasoconstriction
• Altered GFR
• Increased sodium reabsorption
• Increased renin release

Children with OSA demonstrate a ~45% increase in 24-hr urinary noradrenaline.

Effect on Blood Pressure

Catecholamine-driven vasoconstriction leads to:

• Increased peripheral resistance
• Tachycardia
• Sustained daytime hypertension
• Heightened chemoreceptor sensitivity

Evidence

Muscle sympathetic nerve activity (MSNA) is significantly elevated in OSA and decreases with CPAP. Catecholamine levels correlate with hypoxemia severity.

4. Cardiovascular Pathway: Negative Intrathoracic Pressure Load

Mechanism

Obstruction → futile inspiratory efforts → extreme negative intrathoracic pressure. Results:

• Increased LV transmural pressure (↑ afterload)
• Increased venous return to RV (RV distension)
• Septal shift → impaired LV filling (↓ preload)
• Reduced stroke volume during apnoea

Effect on Kidneys

Increased venous return and atrial stretch → continuous ANP/BNP secretion → nocturnal sodium and water loss.

Effect on Blood Pressure

Initial drop (reduced CO) → rebound sympathetic surge → hypertensive peaks after each apnoea.

Evidence

Intrathoracic pressure swings correlate with ANP rises and urinary cGMP elevation.

5. Renal Pathway: RAAS Activation

Mechanism

Intermittent hypoxia + sympathetic stimulation → ↑ renin → ↑ angiotensin II → ↑ aldosterone.

Effect on Kidneys

Although RAAS normally promotes fluid retention, its actions are overwhelmed by high ANP/BNP, leading to increased sodium excretion.

Effect on Blood Pressure

Angiotensin II → vasoconstriction
Aldosterone → fluid retention
→ Hypertension, especially resistant hypertension associated with OSA.

Evidence

OSA patients show higher plasma renin activity, aldosterone, and angiotensin II. CPAP partially reduces RAAS activation.

6. Renal Pathway: Direct Hypoxic Damage to Kidney Tissue

Mechanism

Intermittent hypoxia triggers:

• Reactive oxygen species (ROS)
• HIF activation
• Inflammatory cytokine release
• Renal sympathetic nerve activation

Effect on Kidneys

• Tubular dysfunction
• Impaired urine concentration
• Tubulointerstitial injury
• Reduced renal perfusion
         → Increased nocturnal urine output and sodium loss.

Effect on Blood Pressure

Renal hypoxia contributes to:

• Endothelial dysfunction
• Impaired pressure-natriuresis
• Further sympathetic elevation
• Chronic kidney disease progression

7. Neurological Pathway: Elevated Arousal Threshold

Mechanism

Chronic sleep fragmentation increases homeostatic sleep pressure → higher arousal threshold.

Children enter deep sleep more persistently and struggle to wake even with bladder distension.

Effect on Bladder/Kidneys

• Reduced sensitivity to bladder signals
• Failure to transition from deep sleep when detrusor contraction occurs
         → Enuresis during NREM transitions.

Evidence

Polysomnography shows:

• Higher CAP rates in N3
• Reduced A2/A3 arousals
         Enuretic children exhibit difficulty waking despite bladder signaling.

8. Neurological Pathway: Sympathetic Overactivation

Mechanism

Hypoxia + arousals + respiratory effort → chronic sympathetic overactivation.

Effect on Kidneys

• Altered renal blood flow
• Increased renin
• Sodium retention patterns modified
• Impaired bladder innervation balance

Effect on Bladder

Sympathetic overdrive contributes to:

• Detrusor overactivity
• Bladder hypersensitivity
• Increased urgency and reduced capacity

Effect on Blood Pressure

Central driver of hypertensive patterns in OSA.

9. Bladder Pathway: Detrusor Overactivity and Instability

Mechanism

Intermittent hypoxia induces oxidative damage in bladder smooth muscle:

• Mitochondrial dysfunction
• ROS accumulation
• Altered calcium handling
• Smooth muscle structural change

Effect on Bladder

• Premature detrusor contractions
• Reduced functional capacity
• Bladder wall thickening
         → Overactive bladder phenotype.

Clinical Link to Enuresis

With an elevated arousal threshold, premature detrusor contraction leads to involuntary nocturnal voiding.

Evidence

Severity of OSA correlates with:

• Bladder wall thickness
• Overactive bladder symptom scores
• Time spent below 90% oxygen saturation

10. Metabolic Pathway: Mouth Breathing and Respiratory Alkalosis

Mechanism

Chronic mouth breathing → CO₂ over-exhalation → hypocapnia → respiratory alkalosis

Effect on Kidneys

To compensate, kidneys excrete:

• Bicarbonate
• Minerals including magnesium, sodium, phosphorus, calcium

Systemic Consequences

• Reduced tissue oxygen delivery (left-shifted oxyhemoglobin curve)
• Impaired neuromuscular function
• Reduced cellular ATP production
• Increased vulnerability of bladder and kidney tissues

Evidence

Mouth breathing increases net water and energy loss by 42%. Blood-gas shifts reduce oxygen unloading to tissues despite normal oxygen saturation values.

Integrated Mechanistic Cascade

Airway obstruction →
→ Negative intrathoracic pressure → ANP/BNP release → nocturnal diuresis
→ Hypoxia → cortisol + catecholamines → hypertension + renal changes  
Sleep fragmentation → ADH suppression + high arousal threshold  
Renal hypoxia → impaired concentrating ability  
Bladder oxidative stress → detrusor overactivity  
Mouth breathing → alkalosis → mineral loss → impaired neuromuscular control

Combined outcome:

• Nocturnal polyuria
• Bladder overactivity
• Failure to awaken to bladder signals
         → Nocturnal enuresis

Clinical Implications

Treatment of airway obstruction consistently improves bedwetting through:

• Reduced negative intrathoracic pressure
• Lower ANP/BNP secretion
• Restoration of ADH rhythm
• Reduced sympathetic tone and catecholamines
• Improved RAAS balance
• Normalization of blood pressure patterns
• Improved sleep architecture
• Renal and bladder tissue recovery

Adenotonsillectomy improves enuresis in 68–85% of children with OSA. CPAP in adults reduces nocturia and bedwetting episodes.

Emerging evidence suggests tethered oral tissue release and airway-expansion orthodontics may provide similar improvements by restoring airway patency.

Bedwetting associated with airway obstruction is therefore a physiological disorder, not a behavioural or developmental failure.