Respiratory System

佚名

T he respiratory system's major function is gas exchange, in which air enters the body on inhalation (inspiration), travels throughout the respiratory passages, exchanging oxygen for carbon dioxide at the tissue level, and carbon dioxide is expelled on exhalation (expiration).

The upper airway ― composed of the nose, mouth, pharynx, and larynx ― allows airflow into the lungs. This area is responsible for warming, humidifying, and filtering the air, thereby protecting the lower airway from foreign matter.

The lower airway consists of the trachea, mainstem bronchi, secondary bronchi, bronchioles, and terminal bronchioles. These structures are anatomic dead spaces and function only as passageways for moving air into and out of the lung. Distal to each terminal bronchiole is the acinus, which consists of respiratory bronchioles, alveolar ducts, and alveolar sacs. The bronchioles and ducts function as conduits, and the alveoli are the chief units of gas exchange. These final subdivisions of the bronchial tree make up the lobules ― the functional units of the lungs. (See Structure of the lobule .)

In addition to warming, humidifying, and filtering inspired air, the lower airway protects the lungs with several defense mechanisms. Clearance mechanisms include the cough reflex and mucociliary system. The mucociliary system produces mucus, trapping foreign particles. Foreign matter is then swept to the upper airway for expectoration by specialized fingerlike projections called cilia. A breakdown in the epithelium of the lungs or the mucociliary system can cause the defense mechanisms to malfunction, and pollutants and irritants then enter and inflame the lungs. The lower airway also provides immunologic protection and initiates pulmonary injury responses .

The external component of respiration (ventilation or breathing) delivers inspired air to the lower respiratory tract and alveoli. Contraction and relaxation of the respiratory muscles moves air into and out of the lungs.

Normal expiration is passive; the inspiratory muscles cease to contract, and the elastic recoil of the lungs and the chest wall causes them to contract again. These actions raise the pressure within the lungs to above atmospheric pressure, moving air from the lungs to the atmosphere.

An adult lung contains an estimated 300 million alveoli; each alveolus is supplied by many capillaries. To reach the capillary lumen, oxygen must cross the alveolar capillary membrane.

The pulmonary alveoli promote gas exchange by diffusion ― the passage of gas molecules through respiratory membranes. In diffusion, oxygen passes to the blood, and carbon dioxide, a byproduct of cellular metabolism, passes out of the blood and is channeled away.

Circulating blood delivers oxygen to the cells of the body for metabolism and transports metabolic wastes and carbon dioxide from the tissues back to the lungs. When oxygenated arterial blood reaches tissue capillaries, the oxygen diffuses from the blood into the cells because of an oxygen tension gradient. The amount of oxygen available to cells depends on the concentration of hemoglobin (the principal carrier of oxygen) in the blood; the regional blood flow; the arterial oxygen content; and cardiac output.

Because circulation is continuous, carbon dioxide does not normally accumulate in tissues. Carbon dioxide produced during cellular respiration diffuses from tissues to regional capillaries and is transported by the systemic venous circulation. When carbon dioxide reaches the alveolar capillaries, it diffuses into the alveoli, where the partial pressure of carbon dioxide is lower. Carbon dioxide is removed from the alveoli during exhalation.

For effective gas exchange, ventilation and perfusion at the alveolar level must match closely. (See Understanding ventilation and perfusion .) The ratio of ventilation to perfusion is called the / ratio. A / mismatch can result from ventilation-perfusion dysfunction or altered lung mechanics.

The amount of air reaching the lungs carrying oxygen depends on lung volume and capacity, compliance, and resistance to airflow. Changes in compliance can occur in either the lung or the chest wall. Destruction of the lung's elastic fibers, which occurs in adult respiratory distress syndrome, decreases lung compliance. The lungs become stiff, making breathing difficult. The alveolar capillary membrane may also be affected, causing hypoxia. Chest wall compliance is affected by disorders causing thoracic deformity, muscle spasm, and abdominal distention.

Respiration is also controlled neurologically by the lateral medulla oblongata of the brain stem. Impulses travel down the phrenic nerves to the diaphragm and then down the intercostal nerves to the intercostal muscles between the ribs. The rate and depth of respiration are controlled similarly.

Apneustic and pneumotaxic centers in the pons of the midbrain influence the pattern of breathing. Stimulation of the lower pontine apneustic center (by trauma, tumor, or cerebrovascular accident) produces forceful inspiratory gasps alternating with weak expiration. This pattern does not occur if the vagi are intact. The apneustic center continually excites the medullary inspiratory center and thus facilitates inspiration. Signals from the pneumotaxic center and afferent impulses from the vagus nerve inhibit the apneustic center and “turn off” inspiration.

In addition, chemoreceptors respond to the hydrogen ion concentration of arterial blood (pH), the partial pressure of arterial carbon dioxide (Pa CO 2 ), and the partial pressure of arterial oxygen (Pa O 2 ). Central chemoreceptors respond indirectly to arterial blood by sensing changes in the pH of the cerebrospinal fluid (CSF). Pa CO 2 also helps regulate ventilation by impacting the pH of CSF. If Pa CO 2 is high, the respiratory rate increases; if Pa CO 2 is low, the respiratory rate decreases. Information from peripheral chemoreceptors in the carotid and aortic bodies also responds to decreased Pa O 2 and decreased pH. Either of these changes results in increased respiratory drive within minutes.

PATHOPHYSIOLOGIC MANIFESTATIONS

Pathophysiologic manifestations of respiratory disease may stem from atelectasis, bronchiectasis, cyanosis, and hypoxemia.

Atelectasis

Atelectasis occurs when the alveolar sacs or entire lung segments expand incompletely, producing a partial or complete lung collapse. This phenomenon removes certain regions of the lung from gas exchange, allowing unoxygenated blood to pass unchanged through these regions and resulting in hypoxia. Atelectasis may be chronic or acute, and often occurs in patients undergoing upper abdominal or thoracic surgery. There are two major causes of collapse due to atelectasis: absorptional atelectasis, secondary to bronchial or bronchiolar obstruction, and compression atelectasis.

Absorption atelectasis

Bronchial occlusion, which prevents air from entering the alveoli distal to the obstruction, can cause absorption atelectasis ― the air present in the alveoli is absorbed gradually into the bloodstream, and eventually the alveoli collapse. This may result from intrinsic or extrinsic bronchial obstruction. The most frequent intrinsic cause is retained secretions or exudate forming mucous plugs. Disorders such as cystic fibrosis, chronic bronchitis, or pneumonia increase the risk of absorption atelectasis. Extrinsic bronchial atelectasis usually results from occlusion caused by foreign bodies, bronchogenic carcinoma, and scar tissue.

Impaired production of surfactant can also cause absorption atelectasis. Increasing surface tension of the alveolus due to reduced surfactant leads to collapse.

Compression atelectasis

Compression atelectasis results from external compression, which drives the air out and causes the lung to collapse. This may result from upper abdominal surgical incisions, rib fractures, pleuritic chest pain, tight chest dressings, and obesity (which elevates the diaphragm and reduces tidal volume). These situations inhibit full lung expansion or make deep breathing painful, thus resulting in this disorder.

Bronchiectasis

Bronchiectasis is marked by chronic abnormal dilation of the bronchi and destruction of the bronchial walls, and can occur throughout the tracheobronchial tree. It may also be confined to a single segment or lobe. This disorder is usually bilateral in nature and involves the basilar segments of the lower lobes.

There are three forms of bronchiectasis: cylindrical, fusiform (varicose), and saccular (cystic). (See Forms of bronchiectasis .) It results from conditions associated with repeated damage to bronchial walls with abnormal mucociliary clearance, which causes a breakdown of supporting tissue adjacent to the airways. (See Causes of bronchiectasis .)

In patients with bronchiectasis, sputum stagnates in the dilated bronchi and leads to secondary infection, characterized by inflammation and leukocytic accumulations. Additional debris collects within and occludes the bronchi. Increasing pressure from the retained secretions induces mucosal injury.

Cyanosis

Cyanosis is a bluish discoloration of the skin and mucous membranes. In most populations, it is readily detectable by a visible blue tinge on the nail beds and the lips. Central cyanosis indicates a decreased oxygen saturation of the hemoglobin in arterial blood, which is best observed in the buccal mucous membranes and the lips. Peripheral cyanosis is a slowed blood circulation of the fingers and toes that is best visualized by examining the nail bed area.

Cyanosis is caused by desaturation with oxygen or reduced hemoglobin amounts. It develops when 5 g of hemoglobin is desaturated, even if hemoglobin counts are adequate or reduced. Conditions that result in cyanosis include decreased arterial oxygenation (indicated by low Pa O 2 ), pulmonary or cardiac right-to-left shunts, decreased cardiac output, anxiety, and a cold environment.

An individual who is not cyanotic does not necessarily have adequate oxygenation. Inadequate oxygenation of the tissues occurs in severe anemia, resulting in inadequate hemoglobin concentration. It also occurs in carbon monoxide poisoning, in which hemoglobin binds to carbon monoxide instead of to oxygen. Although assessment of these patients does not reveal cyanosis, oxygenation is inadequate.

Others may appear cyanotic even though oxygenation is adequate ― as in polycythemia, an abnormal increase in red blood cell count. Because the hemoglobin count is increased and oxygenation occurs at a normal rate, the patient may still present with cyanosis.

Cyanosis as a presenting condition must be interpreted in relation to the patient's underlying pathophysiology. Diagnosis of inadequate oxygenation may be confirmed by analyzing arterial blood gases and obtaining Pa O 2 measurements.

Hypoxemia

Hypoxemia is reduced oxygenation of the arterial blood, evidenced by reduced Pa O 2 of arterial blood gases. It is caused by respiratory alterations, whereas hypoxia is a diminished oxygenation of tissues at the cellular level that may be caused by conditions affecting other body systems that are unrelated to alterations of pulmonary functioning. Low cardiac output or cyanide poisoning can result in hypoxia, in addition to alterations of respiration. Hypoxia can occur anywhere in the body. If hypoxia occurs in the blood, it is termed hypoxemia. Hypoxemia can lead to tissue hypoxia.

Hypoxemia can be caused by decreased oxygen content (P O 2 ) of inspired gas, hypoventilation, diffusion abnormalities, abnormal / ratios, and pulmonary right-to-left shunts. The physiologic mechanism for each cause of hypoxemia is variable. (See Major causes of hypoxemia .)

DISORDERS

Respiratory disorders can be acute or chronic. The following disorders include examples from each.

Adult respiratory distress syndrome

Adult respiratory distress syndrome (ARDS) is a form of pulmonary edema that can quickly lead to acute respiratory failure. Also known as shock lung, stiff lung, white lung, wet lung, or Da Nang lung, ARDS may follow direct or indirect injury to the lung. However, its diagnosis is difficult, and death can occur within 48 hours of onset if not promptly diagnosed and treated. A differential diagnosis needs to rule out cardiogenic pulmonary edema, pulmonary vasculitis, and diffuse pulmonary hemorrhage.

Causes

Common causes of ARDS include:

• injury to the lung from trauma (most common cause) such as airway contusion
• trauma-related factors, such as fat emboli, sepsis, shock, pulmonary contusions, and multiple transfusions, which increase the likelihood that microemboli will develop
• anaphylaxis
• aspiration of gastric contents
• diffuse pneumonia, especially viral pneumonia
• drug overdose, such as heroin, aspirin, or ethchlorvynol
• idiosyncratic drug reaction to ampicillin or hydrochlorothiazide
• inhalation of noxious gases, such as nitrous oxide, ammonia, or chlorine
• near drowning
• oxygen toxicity
• sepsis
• coronary artery bypass grafting
• hemodialysis
• leukemia
• acute miliary tuberculosis
• pancreatitis
• thrombotic thrombocytopenic purpura
• uremia
• venous air embolism.

Pathophysiology

Injury in ARDS involves both the alveolar epithelium and the pulmonary capillary epithelium. A cascade of cellular and biochemical changes is triggered by the specific causative agent. Once initiated, this injury triggers neutrophils, macrophages, monocytes, and lymphocytes to produce various cytokines. The cytokines promote cellular activation, chemotaxis, and adhesion. The activated cells produce inflammatory mediators, including oxidants, proteases, kinins, growth factors, and neuropeptides, which initiate the complement cascade, intravascular coagulation, and fibrinolysis.

These cellular triggers result in increased vascular permeability to proteins, affecting the hydrostatic pressure gradient of the capillary. Elevated capillary pressure, such as results from insults of fluid overload or cardiac dysfunction in sepsis, greatly increases interstitial and alveolar edema, which is evident in dependent lung areas and can be visualized as whitened areas on chest X-rays. Alveolar closing pressure then exceeds pulmonary pressures, and alveolar closure and collapse begin.

In ARDS, fluid accumulation in the lung interstitium, the alveolar spaces, and the small airways causes the lungs to stiffen, thus impairing ventilation and reducing oxygenation of the pulmonary capillary blood. The resulting injury reduces normal blood flow to the lungs. Damage can occur directly ― by aspiration of gastric contents and inhalation of noxious gases ― or indirectly ― from chemical mediators released in response to systemic disease.

Platelets begin to aggregate and release substances, such as serotonin, bradykinin, and histamine, which attract and activate neutrophils. These substances inflame and damage the alveolar membrane and later increase capillary permeability. In the early stages of ARDS, signs and symptoms may be undetectable.

Additional chemotactic factors released include endotoxins (such as those present in septic states), tumor necrosis factor, and interleukin-1 (IL-1). The activated neutrophils release several inflammatory mediators and platelet aggravating factors that damage the alveolar capillary membrane and increase capillary permeability.

Histamines and other inflammatory substances increase capillary permeability, allowing fluids to move into the interstitial space. Consequently, the patient experiences tachypnea, dyspnea, and tachycardia. As capillary permeability increases, proteins, blood cells, and more fluid leak out, increasing interstitial osmotic pressure and causing pulmonary edema. Tachycardia, dyspnea, and cyanosis may occur. Hypoxia (usually unresponsive to increasing fraction of inspired oxygen [Fi O 2 ]), decreased pulmonary compliance, crackles, and rhonchi develop. The resulting pulmonary edema and hemorrhage significantly reduce lung compliance and impair alveolar ventilation.

The fluid in the alveoli and decreased blood flow damage surfactant in the alveoli. This reduces the ability of alveolar cells to produce more surfactant. Without surfactant, alveoli and bronchioles fill with fluid or collapse, gas exchange is impaired, and the lungs are much less compliant. Ventilation of the alveoli is further decreased. The burden of ventilation and gas exchange shifts to uninvolved areas of the lung, and pulmonary blood flow is shunted from right to left. The work of breathing is increased, and the patient may develop thick frothy sputum and marked hypoxemia with increasing respiratory distress.

Mediators released by neutrophils and macrophages also cause varying degrees of pulmonary vasoconstriction, resulting in pulmonary hypertension. The result of these changes is a / mismatch. Although the patient responds with an increased respiratory rate, sufficient oxygen cannot cross the alveolar capillary membrane. Carbon dioxide continues to cross easily and is lost with every exhalation. As both oxygen and carbon dioxide levels in the blood decrease, the patient develops increasing tachypnea, hypoxemia, and hypocapnia (low Pa CO 2 ).

Pulmonary edema worsens and hyaline membranes form. Inflammation leads to fibrosis, which further impedes gas exchange. Fibrosis progressively obliterates alveoli, respiratory bronchioles, and the interstitium. Functional residual capacity decreases and shunting becomes more serious. Hypoxemia leads to metabolic acidosis. At this stage, the patient develops increasing Pa CO 2 , decreasing pH and Pa O 2 , decreasing bicarbonate levels, and mental confusion. (See Looking at adult respiratory distress syndrome .)

The end result is respiratory failure. Systemically, neutrophils and inflammatory mediators cause generalized endothelial damage and increased capillary permeability throughout the body. Multisystem organ dysfunction syndrome (MODS) occurs as the cascade of mediators affects each system. Death may occur from the influence of both ARDS and MODS.