Airway resistance

The factors determining the flow of air through the airways are analogous to those determining flow of blood through the vessels and are described by Ohm's law:

Airflow =-

Airflow through the airways is proportional to the gradient between atmospheric pressure and alveolar pressure (DP) and inversely proportional to the airway resistance (R).

Factors determining resistance to airflow are also analogous to those determining the resistance to blood flow and include viscosity, length of the airway, and airway radius. Under normal conditions, the viscosity of the air is fairly constant and the length of the airway is fixed. Therefore, airway radius is the critically important physiological factor determining airway resistance:

Ra-1

Airway resistance is inversely proportional to the radius (r) of the airway to the fourth power. In other words, when the radius is reduced by a factor of two (50%), the airway resistance increases 16-fold. Several factors determine airway resistance, including:

• Airway obstruction

• Bronchial smooth muscle tone

Lung volume. As lung volume increases, airway resistance decreases, that is, as the lungs inflate, the airways expand and become larger. The increase in airway radius decreases airway resistance. Conversely, as lung volume decreases, airway resistance increases. In fact, at very low lung volumes, the small airways may close completely. This is a problem, especially at the base of the lungs, where, due to the weight of the lungs, the airways are less well expanded.

Airway obstruction. Airway obstruction may be caused by several factors including:

• Excess mucus production

• Inflammation and edema of the airway wall

• Airway collapse

Asthma and chronic bronchitis are characterized by overproduction of a thick, viscous mucus (see Figure 17.3, panel b). This mucus blocks the airways and, in effect, reduces the radius of the airways and increases airway resistance. A severe asthmatic attack may be accompanied by formation of mucus plugs, which completely obstruct airflow. Asthma and chronic bronchitis, which are considered chronic inflammatory conditions, are also characterized by inflammation and edema of the airway walls (see Figure 17.3, panel c). This thickening of the airway wall narrows the lumen of the airway and increases airway resistance. Increase in airway resistance due to excess mucus production and inflammation is reversible pharmacologically. The pathophysiology of emphysema involves the breakdown, or destruction, of alveoli. This results in the loss of interdependence, or the effect of radial traction, on airways and leads to airway collapse (see Figure 17.3, panel d). Increase in airway resistance due to this form of lung obstruction is irreversible.

Bronchial smooth muscle tone. Changes in bronchial smooth muscle tone are particularly important in the bronchioles compared to the bronchi. Recall that the walls of the bronchioles consist almost entirely of smooth muscle. Contraction and relaxation of this muscle has a marked effect on the internal radius of the airway. An increase in bronchial smooth muscle tone, or bron-choconstriction, narrows the lumen of the airway and increases resistance to airflow. The activation of irritant receptors in the trachea and large bronchi by airborne pollutants, smoke, and noxious chemicals elicits reflex bronchoc-onstriction. This reflex is mediated by the parasympathetic nervous system, specifically, by the vagus nerve. Acetylcholine released from the vagus nerve stimulates muscarinic receptors on the bronchial smooth muscle to cause bronchoconstriction. This parasympathetic reflex is meant to be a protective response, limiting the penetration of toxic substances deep into the lungs. Parasympathetic stimulation of the lungs also enhances mucus production in an effort to trap inhaled particles.

Bronchoconstriction is also elicited by several endogenous chemicals released from mast cells during an allergy or asthmatic attack. These substances, including histamine and the leukotrienes, may also promote the inflammatory response and edema formation.

A decrease in bronchial smooth muscle tone, or bronchodilation, widens the lumen of the airway and decreases the resistance to airflow. Sympathetic nervous stimulation causes bronchodilation. The adrenergic receptors found on the airway smooth muscle are b2-adrenergic receptors. Recall that nore-pinephrine has a very low affinity for these receptors. Therefore, direct sympathetic stimulation of the airways has little effect. Epinephrine released from the adrenal medulla causes most of this bronchodilation. Epinephrine has a strong affinity for b2-adrenergic receptors. Therefore, during a mass sympathetic discharge, as occurs during exercise or the "fight-or-flight" response, epinephrine-induced bronchodilation minimizes airway resistance and maximizes airflow.

Pharmacy application: pharmacological treatment of asthma

Bronchial asthma is defined as a chronic inflammatory disease of the lungs; it affects an estimated 9 to 12 million individuals in the U.S. Furthermore, its prevalence has been increasing in recent years. Asthma is characterized by reversible airway obstruction (in particular, bronchospasm), airway inflammation, and increased airway responsiveness to a variety of bronchoactive stimuli. Many factors may induce an asthmatic attack, including allergens; respiratory infections; hyperventilation; cold air; exercise; various drugs and chemicals; emotional upset; and airborne pollutants (smog, cigarette smoke).

The desired outcome in the pharmacological treatment of asthma is to prevent or relieve the reversible airway obstruction and airway hyperresponsiveness caused by the inflammatory process. Therefore, categories of medications include bronchodilators and anti-inflammatory drugs.

A commonly prescribed class of bronchodilators is the b2-adr-energic receptor agonists (e.g., albuterol, metaproterenol) that cause relaxation of bronchial smooth muscle and relieve the congestion of bronchial mucosa. Beta two-adrenergic receptor agonists are useful during an acute asthmatic attack and are effective when taken prior to exercise in individuals with exercise-induced asthma. These drugs are usually administered by inhalation or by a nebulizer. Another bronchodilator is ipratropium, an anti-cholinergic drug that blocks muscarinic receptors on the airway smooth muscle. This results in bronchodilation, particularly in large airways. This agent has no effect on the composition or viscosity of bronchial mucus. Also used to treat acute asthmatic attacks, ipratropium is administered by inhalation.

Corticosteroids (e.g., beclomethazone, flunisolide, triamcinolo-ne) have anti-inflammatory and immunosuppressant actions. These drugs are used prophylactically to prevent the occurrence of asthma in patients with frequent attacks. Because they are not useful during an acute attack, corticosteroids are prescribed along with maintenance bronchodilators. These drugs are also administered by inhalation. Cromolyn is another anti-inflammatory agent used prophylactically to prevent an asthmatic attack. The exact mechanism of action of cromolyn is not fully understood; however, it is likely to involve the stabilization of mast cells. This prevents the release of the inflammatory mast cell mediators involved in inducing an asthmatic attack. Cromolyn has proven effective in patients with exercise-induced asthma.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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