MECHANISMS OF DYSPNEA

Respiratory sensations are the consequence of interactions between

the efferent , or outgoing, motor output from the brain to the ventilatory

muscles (feed-forward) and the afferent , or incoming, sensory

input from receptors throughout the body (feedback), as well

as the integrative processing of this information that we infer must

be occurring in the brain ( Fig. 33-1 ) . In contrast to painful sensations,

which can often be attributed to the stimulation of a single

nerve ending, dyspnea sensations are more commonly viewed as

holistic, more akin to hunger or thirst. A given disease state may

lead to dyspnea by one or more mechanisms, some of which may beoperative under some circumstances, e.g., exercise, but not others,

e.g., a change in position.

Motor efferents

Disorders of the ventilatory pump, most commonly increase airway

resistance or stiffness (decreased compliance) of the respiratory system,

are associated with increased work of breathing or a sense of an

increased effort to breathe. When the muscles are weak or fatigued,

greater effort is required, even though the mechanics of the system

are normal. The increased neural output from the motor cortex is

sensed via a corollary discharge, a neural signal that is sent to the

sensory cortex at the same time that motor output is directed to the

ventilatory muscles.

Sensory afferents

Chemoreceptors in the carotid bodies and medulla are activated by

hypoxemia, acute hypercapnia, and acidemia. Stimulation of these

receptors, as well as others that lead to an increase in ventilation, produce

a sensation of air hunger. Mechanoreceptors in the lungs, when

stimulated by bronchospasm, lead to a sensation of chest tightness.

J-receptors, sensitive to interstitial edema, and pulmonary vascular

receptors, activated by acute changes in pulmonary artery pressure,

appear to contribute to air hunger. Hyperinflation is associated with

the sensation of increased work of breathing and an inability to get

a deep breath or of an unsatisfying breath. Metaboreceptors, located in skeletal muscle, are believed to be activated by changes in the local

biochemical milieu of the tissue active during exercise and, when

stimulated, contribute to the breathing discomfort.

Integration: Efferent-reafferent mismatch

A discrepancy or mismatch between the feed-forward message to

the ventilatory muscles and the feedback from receptors that monitor

the response of the ventilatory pump increases the intensity of

dyspnea. This is particularly important when there is a mechanical

derangement of the ventilatory pump, such as in asthma or chronic

obstructive pulmonary disease (COPD).

Anxiety

Acute anxiety may increase the severity of dyspnea either by altering

the interpretation of sensory data or by leading to patterns of

breathing that heighten physiologic abnormalities in the respiratory

system. In patients with expiratory flow limitation, for example, the

increased respiratory rate that accompanies acute anxiety leads to

hyperinflation, increased work and effort of breathing, and a sense

of an unsatisfying breath.

DIFFERENTIAL DIAGNOSIS

Dyspnea is the consequence of deviations from normal function in

the cardiopulmonary systems. These deviations produce breathlessness

as a consequence of increased drive to breathe; increased effort

or work of breathing; and/or stimulation of receptors in the heart,

lungs, or vascular system. Most diseases of the respiratory system

are associated with alterations in the mechanical properties of the

lungs and/or chest wall, frequently as a consequence of disease of

the airways or lung parenchyma. In contrast, disorders of the cardiovascular

system more commonly lead to dyspnea by causing gas

exchange abnormalities or stimulating pulmonary and/or vascular

receptors ( Table 33-2 ).

Respiratory system dyspnea

Diseases of the airways Asthma and COPD, the most common

obstructive lung diseases, are characterized by expiratory airflow

obstruction, which typically leads to dynamic hyperinflation of the

lungs and chest wall. Patients with moderate to severe disease have

increased resistive and elastic loads (a term that relates to the stiffness

of the system) on the ventilatory muscles and increased work

of breathing. Patients with acute bronchoconstriction also complain

of a sense of tightness, which can exist even when lung function is

still within the normal range. These patients commonly hyperventilate.

Both the chest tightness and hyperventilation are probably

due to stimulation of pulmonary receptors. Both asthma and COPD

may lead to hypoxemia and hypercapnia from ventilation-perfusion

(V ˙ /Q) mismatch (and diffusion limitation during exercise with

emphysema); hypoxemia is much more common than hypercapnia

as a consequence of the different ways in which oxygen and carbon

dioxide bind to hemoglobin.

Diseases of the chest wall Conditions that stiffen the chest wall,

such as kyphoscoliosis, or that weaken ventilatory muscles, such as

myasthenia gravis or the Guillain-Barré syndrome, are also associated

with an increased effort to breathe. Large pleural effusions

may contribute to dyspnea, both by increasing the work of breathing

and by stimulating pulmonary receptors if there is associated

atelectasis.

Diseases of the lung parenchyma Interstitial lung diseases, which

may arise from infections, occupational exposures, or autoimmune disorders, are associated with increased stiffness (decreased compliance)

of the lungs and increased work of breathing. In addition,

V ˙ /Q mismatch, and destruction and/or thickening of the alveolarcapillary

interface may lead to hypoxemia and an increased drive to

breathe. Stimulation of pulmonary receptors may further enhance

the hyperventilation characteristic of mild to moderate interstitial

disease.

Cardiovascular system dyspnea

Diseases of the left heart Diseases of the myocardium resulting

from coronary artery disease and nonischemic cardiomyopathies

result in a greater left-ventricular end-diastolic volume and an

elevation of the left-ventricular end-diastolic, as well as pulmonary

capillary pressures. These elevated pressures lead to interstitial

edema and stimulation of pulmonary receptors, thereby causing

dyspnea; hypoxemia due to ˙ V/Q mismatch may also contribute

to breathlessness. Diastolic dysfunction, characterized by a very

stiff left ventricle, may lead to severe dyspnea with relatively mild

degrees of physical activity, particularly if it is associated with mitral

regurgitation.

Diseases of the pulmonary vasculature Pulmonary thromboemoblic

disease and primary diseases of the pulmonary circulation (primary

pulmonary hypertension, pulmonary vasculitis) cause dyspnea via

increased pulmonary-artery pressure and stimulation of pulmonary

receptors. Hyperventilation is common, and hypoxemia may be

present. However, in most cases, use of supplemental oxygen has

minimal effect on the severity of dyspnea and hyperventilation.

Diseases of the pericardium Constrictive pericarditis and cardiac

tamponade are both associated with increased intracardiac and pulmonary

vascular pressures, which are the likely cause of dyspnea in

these conditions. To the extent that cardiac output is limited, at rest

or with exercise, stimulation of metaboreceptors and chemoreceptors

(if lactic acidosis develops) contribute as well.

Dyspnea with normal respiratory and cardiovascular systems

Mild to moderate anemia is associated with breathing discomfort

during exercise. This is thought to be related to stimulation of

metaboreceptors; oxygen saturation is normal in patients with anemia.

The breathlessness associated with obesity is probably due to

multiple mechanisms, including high cardiac output and impaired

ventilatory pump function (decreased compliance of the chest wall).

Cardiovascular deconditioning (poor fitness) is characterized by the

early development of anaerobic metabolism and the stimulation of

chemoreceptors and metaboreceptors.