Respiratory Failure

Definition, etiology, pathogenesis Top

Respiratory failure is a dysfunction of the respiratory system causing impaired pulmonary gas exchange and resulting in hypoxemia (a decrease in the partial pressure of arterial oxygen [PaO2] <60 mm Hg [8 kPa] while breathing room air) or hypercapnia (an increase in the partial pressure of arterial carbon dioxide [PaCO2] >45 mm Hg [6 kPa]). Respiratory failure is classified as hypoxemic respiratory failure or hypercapnic respiratory failure. It may be either acute or chronic.

Hypoxemia

1. Mechanisms of hypoxemia:

1) Mismatch of alveolar ventilation and pulmonary perfusion: Reduction of alveolar ventilation with an unchanged or slightly reduced pulmonary perfusion (eg, due to obstructive or interstitial lung disease, minor atelectases, or alveolar flooding) leads to lower partial pressure of oxygen in those areas of the lungs. Poorly oxygenated blood leaving the alveoli of those areas mixes in the pulmonary veins with oxygenated blood from well-ventilated areas of the lungs. This results in reduction in the oxygen content of the blood in the pulmonary veins, left atrium, left ventricle, and systemic arterial circulation.

2) Shunting of poorly oxygenated blood:

a) Intrapulmonary shunting of poorly oxygenated blood: In the case of preserved perfusion of the nonventilated areas of the lung (eg, due to airway obstruction, major atelectases, or alveolar flooding), poorly oxygenated blood from these areas flows into the pulmonary veins and mixes with oxygenated blood flowing from the well-ventilated alveoli. Higher proportions of poorly oxygenated blood are associated with more severe hypoxemia.

b) Intracardiac shunting of poorly oxygenated blood between the pulmonary and systemic circulations cause hypoxemia that responds poorly to oxygen therapy. It is the oxygen content (bound to hemoglobin plus dissolved oxygen) of deoxygenated blood that causes the hypoxemia. Since very little of the oxygen content of blood is affected by dissolved oxygen and hemoglobin cannot be saturated >100%, shunts are poorly responsive to oxygen therapy.

3) Impaired alveolar-capillary diffusion: This results from interstitial lung diseases, which cause thickening of the alveolar-capillary barrier that leads to impaired oxygen diffusion.

4) Low inhaled partial pressure of oxygen: This occurs at very high altitudes, where atmospheric pressure is relatively low.

2. Consequences of hypoxemia (acute and chronic):

1) Anaerobic metabolism is activated by tissue hypoxia, leading to lactic acidosis, cell death, multiorgan failure, and death (acute).

2) A compensatory physiologic response, including tachycardia, increased blood pressure, increased cardiac output, and hyperventilation. This can be transient, waning with persistent mild hypoxemia.

3) Pulmonary hypertension results from reflex vasoconstriction of the pulmonary arterioles and their increased resistance. It becomes persistent due to pulmonary vascular wall remodeling (acute and chronic).

4) Right ventricular failure caused by right ventricular overload and hypertrophy due to pulmonary hypertension secondary to hypoxemia in the course of diseases of the respiratory system (cor pulmonale; acute and chronic).

5) Cyanosis (acute and chronic).

6) Secondary polycythemia caused by chronic hypoxemia that stimulates the synthesis of erythropoietin in the kidney and thus increases erythropoiesis (chronic).

7) Clubbing of digits and hypertrophic osteoarthropathy (chronic).

Hypercapnia

1. Mechanism of hypercapnia: Alveolar hypoventilation: With inadequate ventilation, CO2 accumulates in the lungs, reducing the pressure gradient across the alveolar-capillary membrane. This is the key factor in the development of hypercapnia, because CO2 crosses the alveolar-capillary membrane approximately 20 times faster than O2. Reduced permeability of this barrier and reduced lung perfusion both have much less effect on CO2 removal than on oxygen uptake.

2. Causes of hypoventilation:

1) Increased load on the respiratory system:

a) Increased airway resistance: Upper airway obstruction (foreign body, laryngeal edema or anaphylaxis, obstructive sleep apnea, loss of consciousness), lower airway obstruction (bronchial smooth muscle contraction and mucosal edema: chronic obstructive pulmonary disease [COPD], asthma, anaphylaxis; bronchial obstruction by secretions or tumor).

b) Reduced lung compliance: Alveolar flooding (pulmonary edema, intra-alveolar bleeding), pneumonia, interstitial lung diseases, atelectasis, dynamic hyperinflation (most frequently in COPD); pleural effusion, pneumothorax.

c) Reduced chest wall compliance: Severe obesity, elevation of the diaphragm (intestinal distention, ascites, paralysis of the diaphragm); chest wall deformity, circumferential burn eschar, or tumors.

d) Demand for increased minute ventilation (relative hypoventilation): Shock, hypovolemia, sepsis, pulmonary embolism.

2) Dysfunction of the nervous system or the respiratory muscles:

a) Impaired activity of the central nervous system respiratory centers: Drug overdose (opioids or sedatives), brainstem damage, central sleep apnea, myxedema coma.

b) Impaired nervous or neuromuscular conduction: Cervical or thoracic spinal cord damage, phrenic nerve damage, Guillain-Barré syndrome, amyotrophic lateral sclerosis, muscle relaxants, myasthenic crisis, tetanus, botulism.

c) Impaired strength of respiratory muscles: Respiratory muscle overload (increased work of breathing), electrolyte disturbances (low potassium, magnesium, or phosphate levels), acidosis, malnutrition, hypoxemia, shock, muscle diseases.

3) Increased physiologic dead space ventilation: Physiologic dead space (anatomic dead space and alveolar dead space) is the volume of inhaled gas that does not take part in gas exchange. It may increase as a consequence of:

a) Increase in the volume of gas remaining in the conducting airways (anatomic dead space).

b) Increased alveolar dead space, which occurs when alveolar pressure is greater than the perfusion pressure to alveolar units due to diminished perfusion to alveoli, overdistension (increased pressure) of compliant alveoli, or both.

4) Increased production of carbon dioxide: Any condition that increases metabolic demand will result in an increase in both oxygen consumption and carbon dioxide production. Unless there is an increase in minute ventilation, there will be a resultant hypercapnia.

3. Consequences of hypercapnia: Hypercapnia will stimulate ventilation via both central and peripheral chemoreceptors. However, in the absence of an appropriate increase in ventilation, hypercapnia will result in other significant effects:

1) Respiratory acidosis.

2) Headache and altered mental status: Confusion, pathologic somnolence, and hypercapnic coma, associated with cerebral vasodilation and increased intracranial pressure.

3) Hypoxic respiratory drive: Chronic respiratory failure with hypercapnia leads to a decreased sensitivity of the respiratory centers in the medulla and pons to increased PaCO2. In such cases, the main impulses stimulating the respiratory centers originate from PaO2 chemoreceptors located mainly in the carotid bodies and the aortic arch. In such patients, too aggressive oxygen therapy and too high PaO2 inhibit the respiratory centers and cause hypoventilation, resulting in the worsening of hypercapnic respiratory failure, and thus leading to coma.