Etiologies and mechanisms of hypercapnia

Respiratory pathway affecting carbon dioxide elimination
Central nervous system ↓	"Won't breathe"
Peripheral nervous system ↓	"Can't breathe"
Respiratory muscles ↓
Chest wall and pleura ↓
Upper airway ↓
Lungs	Abnormal gas exchange: "Can't breathe enough"
Schematic figure representing the respiratory pathway, along which a variety of diseases can affect carbon dioxide elimination and result in hypercapnia. Note that gas exchange abnormalities alone are relatively uncommon causes of hypercapnia, but gas exchange problems in the setting of reduced mechanical capability of the ventilatory pump are very common explanations for acute and chronic hypercapnia.
Mechanism and etiologies of hypercapnia
Mechanism	Etiologies
Decreased minute ventilation (global hypoventilation; extra pulmonary causes)
Decreased central respiratory drive	Sedative overdose (eg, narcotic or benzodiazepine, some anesthetics, tricyclic antidepressants) Encephalitis Stroke Central and obstructive sleep apnea Obesity hypoventilation Congenital central alveolar hypoventilation Brainstem disease Metabolic alkalosis Hypothyroidism* Hypothermia Starvation
Decreased respiratory neuromuscular or thoracic cage function	Primary spinal cord/lower motor neuron/muscle disorders Cervical spine injury or disease (eg, trauma syringomyelia)^¶ Amyotrophic lateral sclerosis Poliomyelitis Guillain-Barré syndrome Phrenic nerve injury Critical illness polymyoneuropathy Myasthenia gravis Muscular dystrophy Polymyositis Tetanus Transverse myelitis (eg, multiple sclerosis) Tick paralysis Acute intermittent porphyria Eaton Lambert syndrome Neuralgic amyotrophy Periodic paralysis Glycogen storage and mitochondrial diseases Respiratory muscle fatigue	Thoracic cage disorders Kyphoscoliosis Thoracoplasty Flail Chest Ankylosing spondylitis Pectus excavatum Fibrothorax	Metabolic disorders^Δ Hypophosphatemia Hypomagnesemia Hypothyroidism Hyperthyroidism
			Toxins, poisoning, drugs Tetanus Dinoflagellate poisoning Shellfish poisoning (red tide) Ciguatera poisoning Botulism Organophosphates Succinylcholine and neuromuscular blockade Procainamide
Increased dead space (gas exchange abnormalities; pulmonary parenchymal causes or airway disorders)
Anatomic	Short shallow breathing
Physiologic	Pulmonary embolism (usually severe) Pulmonary vascular disease (usually severe) Dynamic hyperinflation (eg, upper and lower airway disorders including chronic obstructive pulmonary disease, severe asthma) Endstage interstitial lung disease
Increased carbon dioxide production
	Fever Thyrotoxicosis Increased catabolism (sepsis, steroids) Overfeeding Metabolic acidosis Exercise
Multifactorial
	Upper airway disorder^◊ Severe laryngeal or tracheal disorders (stenosis/tumors/angioedema/tracheomalacia) Vocal cord paralysis Epiglottitis Foreign body aspiration Retropharyngeal disorders Obstructive goiter

This is a comprehensive list of etiologies of hypercapnia that are not listed in order of which is more or less common. Decreased mechanical ventilation can also cause hypercapnic respiratory acidosis (eg, permissive hypercapnia). Importantly, any factor that limits the mechanical function of the ventilatory pump (such as airway obstruction or weak muscles), when combined with a gas exchange abnormality (increased physiological dead space), may lead to hypercapnia. For further details regarding the mechanisms that underlie these pathologies, please refer to the UpToDate topic on mechanisms, causes, and effects of hypercapnia.

* Hyperthyroidism is also a rare cause of respiratory muscle weakness.

¶ Injury or disease process needs to be between cervical spine level 3 and 5 (C3 to 5) for clinically significant diaphragmatic paresis/paralysis to occur.

Δ Hypermagnesemia, hypokalemia, and hypercalcemia can also cause respiratory muscle weakness and contribute to hypercapnia.

◊ Upper airway disorders are rare causes of hypercapnia. They either diminish total ventilation or lead to dynamic hyperinflation and reduced tidal volume while simultaneously causing increased work of breathing and carbon dioxide production.

Graphic 103091 Version 4.0

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Etiologies and mechanisms of hypercapnia