Respiratory failure is a clinical syndrome characterized by severe impairment of primary lung ventilation and/or gas exchange function, leading to hypoxemia and/or CO2 retention, and causing a series of physiological and metabolic disturbances. The diagnosis of respiratory failure is based on arterial blood gas measurements, specifically at sea level, at rest, and breathing room air: arterial oxygen pressure (PaO2) < 60 mmHg or carbon dioxide pressure (PaCO2) > 50 mmHg.
Classification
In clinical practice, classification is usually based on arterial blood gas and the onset speed.
Classification by arterial blood gas
Type I respiratory failure
Type I respiratory failure, also known as hypoxemic respiratory failure, is characterized by PaO2 < 60 mmHg with decreased or normal PaCO2. It is mainly seen in disorders of pulmonary gas exchange (ventilation-perfusion mismatch, diffusion impairment, pulmonary shunt), such as severe pulmonary infections, interstitial lung disease, and acute pulmonary embolism.
Type II respiratory failure
Type II respiratory failure, also known as hypercapnic respiratory failure, is characterized by PaCO2 > 50 mmHg, with or without hypoxemia. The severity of hypoxemia and hypercapnia due to pure ventilation insufficiency is parallel; if there is a gas exchange disorder, hypoxemia is more severe.
Classification by onset speed
Acute respiratory failure
Acute pathogenic factors, such as severe lung disease, trauma, shock, electric shock, and acute airway obstruction, can rapidly impair lung ventilation and/or gas exchange function, leading to respiratory failure quickly. Without prompt intervention, it can be life-threatening due to the body's inability to quickly compensate.
Chronic respiratory failure
Some chronic diseases can gradually worsen respiratory function, eventually leading to respiratory failure over time. This includes chronic obstructive pulmonary disease (COPD), pulmonary tuberculosis, interstitial lung disease, and neuromuscular disorders, and COPD is the most common. In the early stage, there may be hypoxemia with or without hypercapnia, but the body compensates, resulting in mild physiological and metabolic disturbances, allowing for some level of daily activity. Arterial blood gas analysis shows pH within the normal range. Another common clinical scenario is acute exacerbation of chronic respiratory failure, where conditions such as respiratory infections, airway spasms, and pneumothorax cause a rapid deterioration, with significant decreases in PaO2 and/or increases in PaCO2. This presents features of both chronic and acute respiratory failure in terms of pathophysiology and clinical manifestations.
Pathophysiology
Hypoxemic respiratory failure
The main causes of hypoxemic respiratory failure include decreased inspired oxygen pressure (PiO2), reduced alveolar ventilation (VA), ventilation-perfusion (V/Q) mismatch, true shunt, and diffusion impairment.
Low inspired oxygen pressure
Any situation that reduces the inspired oxygen pressure can lead to hypoxemia. According to the alveolar gas equation:
PAO2 = PiO2 -（PACO2/RQ）
PAO2 is the alveolar oxygen pressure, PACO2 is the alveolar carbon dioxide pressure, and RQ is the respiratory quotient (CO2 production/O2 consumption) and is a constant. When inspired oxygen pressure decreases, alveolar oxygen pressure drops, leading to a decrease in arterial oxygen pressure. This is common in conditions like high altitudes above 3000 meters or sudden decreases in PiO2 due to oxygen therapy equipment failure. These situations are easily identifiable clinically.
Hypoventilation
Normal effective alveolar ventilation in adults at rest is about 4 L/min. According to the equation:
PACO2 = 0.863 × VCO2VA
PACO2 is the alveolar carbon dioxide pressure, and VCO2 is the amount of CO2 production per minute and can be considered constant. The formula shows that PACO2 is inversely proportional to VA. Therefore, hypoventilation directly leads to an increase in PACO2. From the alveolar gas equation (where Patm is atmospheric pressure and PH2O is water vapor pressure):
PAO2 = PiO2 -（PACO2/RQ）= FiO2 ×（Patm-PH2O）-（PACO2/RQ）
An increase in PACO2 leads to a decrease in PAO2, but this can be corrected by increasing oxygen concentration.
Ventilation-Perfusion ratio mismatch
Adequate oxygenation and CO2 elimination depend on normal ventilation and diffusion, as well as a proper ratio between alveolar ventilation and blood flow. The normal V/Q ratio at rest is about 0.8. Mismatches occur in two main forms:
Ventilation insufficiency: conditions such as alveolar collapse, pneumonia, atelectasis, and pulmonary edema reduce ventilation, decreasing the V/Q ratio. Unoxygenated venous blood (pulmonary artery blood) flows directly into arterial blood (pulmonary vein) through alveolar capillaries or shunts, which is termed functional shunt.
Perfusion insufficiency: conditions such as pulmonary embolism, reduced cardiac output, and emphysema increase the V/Q ratio, causing dead-space like ventilation. V/Q mismatch affects oxygenation more than CO2 elimination. CO2 diffuses into the blood 20 times faster than O2. The oxygen dissociation curve is S-shaped, and normal alveolar capillary blood oxygen saturation is already on the plateau, unable to carry more oxygen to compensate for the decrease in oxygen content in low PaO2 areas. The CO2 dissociation curve is linear within the physiological range, facilitating compensation from well-ventilated areas to poorly ventilated areas, expelling sufficient CO2 without causing CO2 retention.
True shunt
True shunt is also known as anatomic shunt, where V/Q is 0, meaning venous blood bypasses gas exchange and enters the arterial system, which is an extreme case of V/Q mismatch. The ratio of blood flow through shunt alveoli to cardiac output is called shunt fraction. Normal shunt fraction is less than 10%. An increase in shunt fraction leads to decreased oxygenation. True shunt, where blood flows through non-ventilated alveoli without gas exchange, makes increasing oxygen concentration ineffective in correcting hypoxemia, making it a major cause of refractory hypoxemia. Increased shunt fraction is seen in alveolar filling diseases (pneumonia, pulmonary edema), alveolar collapse (atelectasis), small airway obstruction (asthma), and abnormal communication between pulmonary capillaries (arteriovenous malformations).
Diffusion impairment
This refers to the impaired physical diffusion of gases like O2 and CO2 across the alveolar-capillary membrane. It is common in interstitial lung diseases. The rate of gas diffusion depends on the pressure difference across the alveolar membrane, gas diffusion coefficient, diffusion area, thickness, and permeability of the alveolar membrane, as well as the contact time between blood and alveoli, cardiac output, hemoglobin content, and V/Q ratio. The diffusion coefficient of CO2 is about 20 times that of O2, and the pressure difference across the diffusion membrane is 1/10 that of O2, making the actual diffusion rate of CO2 2 times that of O2. Therefore, diffusion impairment often only causes hypoxemia without CO2 retention. In practice, diffusion impairment rarely causes severe hypoxemia alone because, at rest, blood in alveolar capillaries contacts alveoli for about 0.72 seconds, while O2 completes gas exchange in 0.25 - 0.3 seconds, indicating strong compensatory diffusion capacity.
Hypercapnic respiratory failure
Hypercapnic respiratory failure can result from increased CO2 production and reduced alveolar ventilation:
Increased CO2 production
Conditions such as fever, overfeeding, and sepsis can increase CO2 production. However, due to compensatory mechanisms, increased CO2 production leads to increased minute ventilation, increasing CO2 excretion. Therefore, hypercapnic respiratory failure due to increased CO2 production alone is uncommon.
Decreased alveolar ventilation
Reduced alveolar ventilation leading to decreased CO2 excretion is the main factor causing hypercapnic respiratory failure. According to the formula:
PACO2 = 0.863 × VCO2/VA
Where VA = MV - VD, MV is minute ventilation, and VD is dead space ventilation. Therefore, decreased alveolar ventilation is related to decreased minute ventilation and/or increased dead space. Decreased minute ventilation can be further divided into obstructive and restrictive ventilatory dysfunction. Obstructive conditions include COPD, asthma, and mucus plugging, while restrictive conditions include neuromuscular diseases causing respiratory muscle weakness, pneumothorax, pleural effusion, abdominal hypertension, and obesity.
To be continued