Pathophysiology

The respiratory system is responsible for oxygen and carbon dioxide exchange between the blood and the atmosphere. Respiratory failure occurs when this exchange fails and metabolic demands for oxygen and body system acid-base stabilisation are not maintained, creating a ventilation-perfusion mismatch. Failure of oxygen exchange results in the development of severe hypoxaemia with cellular anoxia and tissue asphyxia. This can occur with all forms of lung disease, including fluid filling of alveolar spaces; collapse of alveolar spaces; re-distribution of blood flow from functioning alveolar units (shunting); loss of blood flow to alveolar tissue (e.g., pulmonary embolism); underlying loss of pulmonary tissue (e.g., emphysema, trauma, fibrosis); and thickening or fluid build-up at alveolar membranes that inhibits gas exchange (e.g., pneumonia). Chronic hypoxia in patients with chronic respiratory failure stimulates increases in the number of circulating red blood cells (erythrocytosis). Failure of carbon dioxide exchange results in hypercapnic respiratory failure, causing increased carbon dioxide in arterial blood and respiratory acidosis. Carbon dioxide accumulation leads to carbonic acid accumulation within the tissues, resulting in chronic respiratory acidosis. Renal bicarbonate retention occurs to compensate for this and results in chronic respiratory failure. Hypercapnic respiratory failure occurs with lung disorders that limit exchange of carbon dioxide from the blood to the atmosphere. These lung disorders include poor ventilatory muscle function, as occurs with neuromuscular disorders (e.g., Guillain-Barre, drug over-dose); obstruction of airways and alveoli (e.g., asthma, pulmonary oedema); secretions in the small airways and alveoli (e.g., chronic obstructive pulmonary disease, cystic fibrosis); and chest wall abnormalities (e.g., traumatic flail chest, kyphoscoliosis). Respiratory factors

Acute pulmonary vascular occlusion can result in ventilation-perfusion mismatch and respiratory failure due to insufficient blood flow to functioning alveoli. Massive pulmonary artery embolisation may cause high right-sided after-load pressures leading to cardiac dysfunction and inability of the heart to circulate adequate blood volume. Pneumothorax can lead to respiratory failure if there is not enough lung reserve to compensate for the collapsed lung or lung segment. This would typically occur in the setting of pre-existing pulmonary dysfunction. Bilateral pneumothoraces can cause catastrophic respiratory failure and rapid cardiac arrest. Fluid or blood accumulation in the pleural space (pulmonary effusion) may lead to compression of pulmonary tissues and loss of pulmonary function, causing respiratory failure. Effusion can occur secondary to infection, malignancy, trauma, cardiac failure, and collagen vascular disease, as well as many other conditions. Destruction or infiltration of alveoli reduces the surface area available for gas exchange. Emphysema causes alveolar destruction, and the bullae that are formed occupy intrathoracic space without contributing to gas exchange. Respiratory failure results from

acute or eventual loss of the baseline number of alveolar units. Infiltration or filling of alveoli with fluid is a frequent cause of acute respiratory failure. Conditions that cause alveolar filling include pneumonia, pulmonary oedema, and pulmonary haemorrhage. Alveolar haemorrhage can occur with Goodpasture's syndrome, Wegener's granulomatosis, and trauma. Fluid-filling of alveoli leads to inability of these alveoli to provide gas exchange with the blood, a condition referred to as intra-pulmonary shunting. Acute respiratory distress syndrome resulting from trauma, hypo-perfusion, or direct insult is a form of alveolar infiltration and injury. Acute upper airway obstruction (e.g., from foreign body aspiration, acute epiglottitis, anatomical abnormalities, anaphylaxis) can inhibit air flow into the lungs and cause respiratory failure. Lower airway obstruction (e.g., from asthma, chronic obstructive pulmonary disease, cystic fibrosis) is more common and involves constriction or mucous blockage of intermediate-size bronchioles. Pulmonary embolus can occur as a result of hypercoagulability from clotting cascade diseases or abnormalities. Exposure to toxic fumes can lead to damage of the upper airway, lower airway, or alveoli. Industrial gases such as chlorine are an example. The most common inhalation injury is smoke inhalation, where particulate matter and gases are intermixed and can cause upper airway and lower airway inflammation resulting in respiratory failure. Toxic gases such as carbon monoxide and hydrogen sulphide are exchanged in the lungs, yet result in asphyxia by inhibiting the ability of the blood to effectively extract oxygen from the lungs, as well as causing cellular metabolic damage (cellular asphyxia).

Non-respiratory factors

Poor perfusion of the brain, heart, and lungs (e.g., from haemorrhagic hypovolaemia, dehydration hypovolaemia, septic shock, cardiogenic shock, severe anaemia) can result in respiratory failure by reducing blood oxygenation and depressing CNS respiratory centres. Ventilation with pulmonary gas exchange is dependent on diaphragm and chest wall muscle functioning. Neurological disorders inhibiting respiratory muscle function limit ventilation and can cause respiratory failure. Examples include Guillain-Barre syndrome and myasthenia gravis. Muscular dystrophy is an example of a disorder that results in muscle function abnormalities that limit ventilation and can result in respiratory failure. Opiate and sedative medicines decrease respiratory drive in the CNS, with resulting limited ventilatory effort. Injuries, disease, or insult of the CNS can result in loss of respiratory drive and secondary respiratory failure. Examples include infiltrating and mass cancers of the CNS, head injury with haemorrhagic mass effect, direct brain injury, infections, primary CNS disorders, and cerebrovascular accident.

Traumatic causes

Direct thoracic injury may result in a number of abnormalities that can lead to respiratory failure. Direct brain injury can result in loss of respiratory drive.

Spinal injury can result in loss of peripheral nerve function and the lack of ability to ventilate.