Alveolar Hypoventilation

Alveolar hypoventilation is a condition characterized by inadequate alveolar ventilation relative to metabolic carbon dioxide production, resulting primarily in hypercapnia and secondarily in hypoxemia. It represents one of the fundamental pathophysiological mechanisms of respiratory insufficiency, particularly hypoxemic–hypercapnic (type II, global) respiratory failure.

Respiratory Failure

In contrast to respiratory failure caused by ventilation–perfusion mismatch or diffusion impairment, alveolar hypoventilation is typically associated with a normal alveolar–arterial oxygen gradient (A–aDO₂).

Epidemiology

Epidemiological data show that the incidence of acute RI according to current criteria is approximately 8 cases per 100,000 population. Chronic lung diseases, such as COPD , bronchial asthma and others, are very common in the population and lead to the development of chronic RI in approximately 5% of cases .

Alveolar hypoventilation occurs across all age groups but is most commonly observed in patients with chronic lung disease, neuromuscular disorders, obesity, or central nervous system depression. It plays a significant role in the development of chronic respiratory insufficiency in patients with chronic obstructive pulmonary disease (COPD), bronchial asthma, obesity hypoventilation syndrome, and various neuromuscular diseases.

Definition

Alveolar hypoventilation is defined as a reduction in alveolar ventilation (V̇A) that is insufficient to maintain normal arterial carbon dioxide tension. The condition is characterized by:

• increased PaCO₂ (hypercapnia),
• decreased PaO₂ (hypoxemia),
• normal or only mildly increased A–aDO₂.

From a pathophysiological perspective, alveolar hypoventilation represents a primary disorder of ventilation, rather than a disorder of diffusion or pulmonary perfusion.

Etiology

The causes of alveolar hypoventilation can be divided into two major categories:

1. Central Causes (Impaired Respiratory Drive)

• Depression of the central nervous system (Opioids, sedatives, anesthetics)
• traumatic brain injury
• cerebrovascular accidents
• neuroinfections
• congenital or acquired central hypoventilation syndromes

2. Peripheral Causes (Failure of the Ventilatory Pump)

• Neuromuscular disorders (Guillain-Barré syndrome, myasthenia gravis, muscular dystrophies)
• spinal cord injuries
• phrenic nerve paralysis
• chest wall deformities (kyphoscoliosis)
• Distrupted pleural space
• obesity hypoventilation syndrome,
• respiratory muscle fatigue
• severe upper or lower airway obstruction.

Pathophysiology

The fundamental mechanism of alveolar hypoventilation is a reduction in alveolar ventilation relative to carbon dioxide production.

Mechanisms Leading to Hypercapnia

Under steady-state conditions:

• arterial PaCO₂ is directly proportional to CO₂ production,
• arterial PaCO₂ is inversely proportional to alveolar ventilation.

A decrease in alveolar ventilation therefore results in carbon dioxide retention and the development of respiratory acidosis.

Mechanisms Leading to Hypoxemia

Hypoxemia in alveolar hypoventilation occurs as a consequence of:

• reduced alveolar oxygen tension,
• without significant ventilation–perfusion mismatch,
• and without impairment of diffusion across the alveolar–capillary membrane.

As a result, the A–aDO₂ remains normal, which is a key diagnostic feature distinguishing alveolar hypoventilation from other causes of respiratory insufficiency.

Clinical Presentation

Clinical manifestations depend on the severity and rate of onset of hypoventilation.

Early manifestations include:

• hypoventilation,
• fatigue,
• daytime somnolence,
• morning headaches,
• reduced exercise tolerance.

Manifestations of hypercapnia:

• headache,
• tremor,
• impaired concentration,
• somnolence progressing to coma,
• increased intracranial pressure in severe cases.

Manifestations of hypoxemia:

• cyanosis,
• tachycardia,
• dyspnea,
• psychomotor agitation.

Diagnostics

The cornerstone of diagnosis is arterial blood gas analysis, which typically demonstrates:

• elevated PaCO₂,
• decreased PaO₂,
• normal A–aDO₂,
• respiratory acidosis (acute) or compensated respiratory acidosis (chronic).

Additional diagnostic steps include:

• detailed medical history (drug use, neurological symptoms, obesity),
• physical examination,
• imaging studies (chest X-ray, CT),
• pulmonary function testing,
• neurological evaluation when indicated.

Treatment

Oxygen Therapy

Management of alveolar hypoventilation is primarily directed at treating the underlying cause.

Key therapeutic principles include:

• ensuring airway patency,
• ventilatory support (non-invasive or invasive, depending on severity),
• cautious oxygen therapy, particularly in chronic hypercapnic patients,
• treatment of the underlying neurological, muscular, or pulmonary disorder,
• respiratory muscle rehabilitation.

In chronic conditions, long-term ventilatory support may be required.

Alveolar Hypoventilation in Children

In pediatric patients, alveolar hypoventilation most commonly occurs in association with:

• congenital neuromuscular disorders,
• severe central nervous system infections,
• congenital central hypoventilation syndrome,
• upper airway obstruction.

Children are at higher risk of rapid decompensation due to limited respiratory reserve.

References

• Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease. Elsevier.
• Hammer GD, McPhee SJ (eds.). Pathophysiology of Disease: An Introduction to Clinical Medicine. McGraw-Hill Education, 2014.
• Maruna P. Examination Tests from Pathological Physiology. Karolinum, 2015.