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Pathology of External Respiration

Pathologia systematis respirationis externae

For medical students2 min readUpdated 2026-10-10

Pathology of external respiration refers to a group of standard disorders characterized by impaired gas exchange between the air in pulmonary alveoli and the blood. These disorders are driven by disruptions in ventilation, perfusion, or gas diffusion along their partial pressure gradients.

External respirationGas exchange between alveoli and capillaries across the blood-air barrier.

Pressure gradientThe difference in partial pressure—the main driving force for gas diffusion in the body.

HypoventilationA condition where the actual alveolar ventilation volume falls below the body's metabolic demands.

Tissue respirationGas exchange between blood and tissues, alongside cellular oxygen consumption.

The Essence of Respiration and Its Types

Respiration is a vital and continuous process of gas exchange, primarily involving oxygen (O2) and carbon dioxide (CO2). The primary physical mechanism underlying this exchange is bidirectional diffusion. Diffusion always occurs strictly along a partial pressure gradient: gas molecules spontaneously move from a zone of higher pressure to a zone of lower pressure.

In medical science and pathophysiology, respiration is traditionally divided into two major interrelated stages:

External respiration. This is the fundamental stage where bidirectional diffusion of gases takes place. Oxygen and carbon dioxide cross a specialized barrier—the blood-air (alveolocapillary) membrane. On one side of this membrane is the air within the pulmonary alveoli, and on the other is the blood flowing through the dense capillary network of the interalveolar septa.
Tissue respiration (often called internal respiration). This stage involves bidirectional gas diffusion directly at the level of internal organs, between capillary blood and the internal environment of body tissues. Furthermore, this term has a strictly biochemical meaning: tissue respiration refers to the direct utilization of O2 molecules by cells during their complex internal metabolism.

Main Forms of External Respiration Disorders

The pathology of the external respiration system includes several typical forms. Each is inextricably linked to the failure of a specific link ensuring normal gas exchange in lung tissue. The four key categories of disorders are:

Alveolar ventilation disorders. The problem lies in impaired delivery of fresh air to the alveolar space or hindered removal of air from it.
Pulmonary perfusion disorders. In this case, blood flow in the capillaries surrounding the alveoli is impaired, meaning the delivered air cannot fully participate in gas exchange with the bloodstream.
Impairment of the ventilation-perfusion ratio (VA/Q mismatch). Normally, incoming airflow and circulating blood flow must be strictly balanced. If this delicate ratio is disrupted, overall respiratory efficiency drops sharply.
Gas diffusion disorders. Obstacles arise that hinder the free passage of O2 and CO2 directly across the alveolocapillary (blood-air) membrane.

Alveolar Ventilation Disorders

Among all potential external respiration disorders, ventilation problems carry special clinical significance. Globally, they are divided into two opposite groups: alveolar hyperventilation and alveolar hypoventilation.

Alveolar hypoventilation is a typical pathological form of external respiration where the actual (real) volume of alveolar ventilation per unit of time is lower than the body requires under given conditions. In other words, the lungs physically cannot keep up with the body's current demand for gas renewal.

Alveolar hypoventilation never occurs without a cause. It is always driven by two major groups of factors:

Disorders of external respiration biomechanics. This group includes impairments of the respiratory apparatus itself that prevent the normal physical execution of inhalation and exhalation.
Disorders of external respiration regulation. Here, the root of the problem lies in the disruption of regulatory signals controlling the breathing process.

Mnemonic

To easily remember the four types of external respiration disorders, use the mnemonic VPDD: Ventilation (air didn't reach), Perfusion (blood didn't arrive), Proportion (ventilation-perfusion mismatch), Diffusion (gas didn't cross the membrane).

Frequently asked questions

Which specific biomechanical disorders of external respiration lead to hypoventilation?

Decreased alveolar ventilation can be caused by disorders of external respiration biomechanics, which include:

Airway obstruction — impaired airway patency.
Impaired lung compliance — restrictive disorders.

What is the pathogenesis and consequences of ventilation-perfusion ratio abnormalities?

The pathogenesis involves a mismatch between blood flow and ventilation in areas of the lungs or the lungs as a whole. This mechanism leads to respiratory failure.

Consequences include:

Hypoxemia — develops due to ventilation-perfusion imbalances.
Forms presenting with both hypoxemia and hypercapnia may occur due to insufficient alveolar ventilation.
Pulmonary cyanosis develops secondary to alveolar hypoventilation and ventilation-perfusion mismatch.
In COPD: areas with low VA/Q contribute primarily to hypoxemia; areas with high VA/Q increase physiological dead space and require a compensatory increase in total ventilation to maintain normal PaCO2.

What causes impaired gas diffusion across the blood-air membrane?

Impaired gas diffusion across the blood-air membrane is associated with the following conditions and mechanisms:

Severe pulmonary parenchymal disease, leading to parenchymal respiratory failure. Examples include generalized infection, fluid aspiration, bronchiolitis, toxic gas inhalation, pulmonary edema, and shock.
Edema of the blood-air membrane in hypothyroid coma, which hinders gas diffusion.
Interstitial edema and impaired gas diffusion across a thickened alveolocapillary membrane in chronic systolic heart failure.
Damage to the alveolocapillary membrane — leading to reduced respiratory surface area and decreased pulmonary diffusing capacity.

What central regulatory disorders of external respiration cause hypoventilation?

Alveolar hypoventilation can be caused by disorders in the regulatory mechanisms of external respiration, divided into three groups:

Centrogenic (neurogenic) — damage to the respiratory center; includes pathology of the respiratory center and CNS pathways, such as birth trauma and brain tumors.
Afferent — insufficient or excessive afferent input to the respiratory center neurons. Excessive inhibitory afferentation can suppress respiratory center activity; causes include severe chest or airway pain, excessive irritation of the airway mucosa, inhalation of irritants, thermal injury, acute bronchitis, and tracheitis.
Efferent — impaired innervation of the respiratory muscles, including impaired impulse transmission at the neuromuscular junctions of the intercostal muscles and diaphragm; examples include poliomyelitis, myasthenia gravis, and polyneuritis.

What factors lead to pulmonary perfusion disorders?

Pulmonary perfusion disorders are recognized as a mechanism impairing the gas-exchange function of the lungs. Confirmed factors and mechanisms include:

Circulatory failure — decreased pulmonary blood flow associated with circulatory failure in hypothyroid coma.
Pulmonary microcirculatory disorders — endothelial injury in microvessels, hemostatic disorders with thrombohemorrhagic syndrome, and intravascular, transmural, and extravascular microcirculatory disturbances.
Decreased circulating blood volume (CBV) and increased blood viscosity — lead to central, tissue, and microcirculatory disturbances; respiratory hypoxia is listed among the consequences.
Hemothorax, pneumothorax, and intrapulmonary hematoma during chest trauma alter pulmonary vascular resistance; pneumothorax and hemothorax exacerbate respiratory and circulatory disorders.

What is the main driving force for gas exchange during respiration?

The main driving force is the partial pressure gradient. Thanks to this pressure difference, oxygen and carbon dioxide diffuse across biological barriers.

What is the fundamental difference between external and tissue respiration?

External respiration is gas exchange between alveolar air and pulmonary capillary blood. Tissue respiration is gas exchange between blood and tissues, as well as the consumption of oxygen by cells to maintain metabolism.

What is the blood-air membrane?

It is a specialized barrier (alveolocapillary membrane) through which bidirectional gas exchange occurs between alveolar air and blood in the interalveolar septa.

What are the main causes of alveolar hypoventilation?

Decreased alveolar ventilation is caused by two main groups of factors: disorders of external respiration biomechanics and disruptions in its regulatory mechanisms.

Go deeper

Detailed analysis of factors causing disorders of external respiration biomechanics.
Mechanisms of external respiration regulatory disorders.
Pathogenesis of alveolar hyperventilation and its systemic consequences.
Causes of impaired gas diffusion across the blood-air membrane.
Changes in the ventilation-perfusion ratio in various pathologies.