Ventilation is determined by the variables in the following equation:

F = P/R

where F is the bulk flow of air, P is the difference in pressure between the atmosphere and the alveoli, and R is the resistance offered by the conducting airways.

Ventilation is controlled by the respiratory center in the lower brainstem areas of the medulla and pons. In the medulla, there are inspiratory and expiratory neurons that fire at opposite times in a preset pattern of rate and rhythm. Respiratory neurons drive ventilation by exciting motor neurons that innervate the main muscle of inspiration (the diaphragm) and the accessory muscles (the intercostal muscles).

The rate of diffusion of a gas (e.g., oxygen and carbon dioxide) is determined with the following equation:

where D is the rate of diffusion, X_a is the concentration of gas in the alveolus, X_c is the concentration of gas in the capillary, SA is the surface area available for diffusion, T is the temperature of the solution, d is the distance across which diffusion must occur, and k is a physical constant that takes into account nonvariable characteristics of the gas such as its molecular weight and its specific solubility coefficient.

Oxygen is carried in the blood in dissolved form and bound to hemoglobin. The amount of oxygen dissolved in the blood depends on the partial pressure of oxygen in the air entering the alveoli and the solubility of oxygen. Normally the dissolved amount carried is small (only approximately 3 mL/L). Instead, most oxygen (98%) is carried bound to hemoglobin.

Hemoglobin is a protein molecule composed of four subunits, each combining a globulin molecule with a molecule of iron. Each iron molecule has a binding site for oxygen. Dissolved oxygen combines with hemoglobin until all four sites are saturated. At normal arterial oxygen concentration of 100 mm Hg,
nearly 100% of hemoglobin molecules are saturated with oxygen. Even in the venous blood, with a reduced oxygen concentration of 40 mm Hg, hemoglobin is still at least 75% saturated with oxygen (Fig. 14-3). The ability of hemoglobin to bind oxygen is reduced by increased hydrogen ion concentration, increased temperature, and increased amount of a substance produced by red blood cells during glycolysis, 2,3-diphosphoglycerate (DPG). A reduced affinity for oxygen means that hemoglobin releases oxygen to the tissues more readily. Increases in hydrogen ion, temperature, and DPG occur during periods of increased metabolism; therefore, decreased hemoglobin affinity releases more oxygen to a cell and allows it to meet its elevated metabolic demands.

The pulmonary circulation consists of deoxygenated blood traveling in the pulmonary artery from the right side of the heart. This blood perfuses the respiratory portions of the lungs and participates in the exchange of oxygen and carbon dioxide across the capillaries and alveoli. After picking up oxygen and releasing carbon dioxide, the blood returns to the heart by way of the pulmonary vein. Pressure and resistance to flow in the pulmonary circulation are usually low, with a mean pulmonary pressure of approximately 12 mm Hg compared with a mean systemic pressure of approximately 90 mm Hg. The pulmonary circulation is compliant and can accommodate large variations in blood volume. Therefore, the pulmonary circulation can act as a reservoir for blood that can be called upon in times of decreased systemic blood volume or pressure.

The bronchial circulation carries blood from the left side of the heart to the lungs through the thoracic aorta. The bronchial circulation accounts for approximately 8% to 9% of the total cardiac output. Blood in the bronchial circulation is well oxygenated and supplies oxygen to the structures of the lungs not involved in the exchange of gases, including the connective tissue and the large and small bronchi. Blood returns to the left side of the heart through the pulmonary vein. Returning bronchial blood is deoxygenated because it has been used by metabolically active cells of the lungs but has not been involved in gas exchange. The deoxygenated blood mixes with the well-oxygenated blood coming from the pulmonary circulation also back to the left side of the heart, and slightly reduces the overall oxygen concentration of that blood.

Spirometry is the measurement of the volume of air moving into and out of the lungs and is measured as an individual inhales and exhales into a closed chamber. It is used to determine lung volumes, including tidal, inspiratory reserve, expiratory reserve, and residual volumes, and, calculated from these, vital capacity (Fig. 14-4). The average values presented in the figure for each of these volumes are for an adult male. Values for adult females are approximately 20% to 25% less.

Pulse oximetry is a noninvasive method that uses infrared technology to measure the percentage of hemoglobin that is saturated with oxygen. A transducer placed on an extremity detects light absorption by hemoglobin during pulsatile arterial waves and a computer translates it into a percentage. The normal range for oxygen saturation (SPO₂) is 95% to 100%. Inaccurate readings may be caused by excessive movement, nail polish, and conditions that alter perfusion such as shock or hypovolemia.

Arterial blood gases (ABGs) offer information about pH and the amount of oxygen, carbon dioxide, and bicarbonate in the blood. Normal values are:

Measurement of the amount of exhaled carbon dioxide may be done by treated paper which changes color in the presence of acid or via spectography. This test is useful in determining the effectiveness of ventilation and may actually help identify impending respiratory depression.

A chest x-ray offers information about structural abnormalities of the lung. For example, atelectasis, consolidation, densities, hyperinflation, edema, or collapsed areas offer valuable information for the diagnosis of respiratory problems.

Compression atelectasis occurs when a source outside the alveolus exerts enough pressure on the alveolus to collapse it. This occurs if the chest wall is punctured or opened because atmospheric pressure is greater than the pressure holding the lungs expanded (pleural pressure), and with exposure to atmospheric pressure the lungs will collapse. Compression atelectasis can also occur if there is pressure exerted on the lungs or alveoli from a growing tumor, abdominal distention, or edema and swelling of the interstitial space around an alveolus.

Absence of air in the alveolus results in absorption atelectasis. If flow of air into an alveolus is blocked, the air currently inside eventually diffuses out and the alveolus collapses. Blockage usually occurs after mucus buildup and obstruction of airflow through a bronchus supplying a given group of alveoli. Any situation that results in mucus accumulation, such as cystic fibrosis, pneumonia, or chronic bronchitis, increases the risk of absorption atelectasis. Surgery is also a risk factor for absorption atelectasis because of the mucus-producing effects of anesthesia as well as a resultant hesitancy to cough up accumulated mucus after surgery. This is especially true if the surgery was in the abdominal or thoracic area, where pain associated with coughing is intense. Prolonged bed rest after surgery increases the risk of developing absorption atelectasis, because lying down causes a pooling of mucus secretions in dependent areas of the lung, decreasing ventilation to those areas. Mucus accumulation increases the risk of pneumonia because mucus can act as a breeding ground for growth of microorganisms.

Absorption atelectasis can also be caused by anything that reduces the production or concentration of surfactant. Without surfactant, surface tension in the alveolus is high, increasing the likelihood of alveolar collapse. Premature birth is associated with a reduction in surfactant and a high incidence of
absorption atelectasis. Near drowning may dilute out surfactant and thus may be associated with absorption atelectasis as well.

Damage to the type II alveolar cells that produce surfactant can also lead to absorption atelectasis. These cells are destroyed by the breakdown of the alveolar wall that occurs during some forms of respiratory disease, as well as by high oxygen therapy for a period longer than 24 hours. With loss of these cells, surfactant production is reduced.

The pulmonary circulation is usually a low-pressure, low-resistance circulation. Anything that causes (1) a prolonged increase in pulmonary blood flow, (2) an increase in pulmonary resistance to flow, or (3) an impediment in pulmonary vascular outflow can result in pulmonary hypertension.

Pulmonary hypertension can make it more difficult for the right side of the heart to pump. A type of heart failure called cor pulmonale can result. Cor pulmonale is right-sided heart failure caused by chronic lung disease. Pulmonary hypertension can also result in pulmonary edema because the capillary hydrostatic force favoring filtration is increased. Edema of the pulmonary interstitial space leads to a decreased diffusion rate of oxygen from the alveolus to the capillary because of increased distance for diffusion.

Although the upper respiratory tract is directly exposed to the environment, infections are uncommon and seldom progress to lower respiratory tract infections involving the lower airways and alveoli. Protective mechanisms abound throughout the respiratory tract to prevent infection. The cough reflex expels foreign bodies and microorganisms, and removes accumulated mucus. The mucociliary blanket consists of cells, located upwards from the level of the bronchi, which make mucus, and cilia cells that line the mucus-producing cells. The mucus-producing cells trap foreign particles, and the cilia beat rhythmically to propel the mucus and any trapped particles up the respiratory tree to the nasopharynx, where they can be expelled as sputum, blown out the nose, or swallowed. This complex is sometimes referred to as the mucociliary escalator system. The cilia are delicate structures that can be paralyzed or injured by a variety of noxious stimuli, including cigarette smoke, as described later.

If microorganisms evade these defense mechanisms and colonize the upper respiratory tract, a third important line of defense, the immune system, is in position to prevent their passage to the lower respiratory tract. This response is mediated by lymphocytes, but also involves other white blood cells such as macrophages and neutrophils brought to the area by the inflammatory process. If there is a breakdown of a defense mechanism of the respiratory system or if the microorganism is especially virulent, a lower respiratory tract infection can result.

Cigarette smoke is known to alter the effectiveness of some respiratory defense mechanisms. Products of cigarette smoke stimulate mucus production while paralyzing the cilia. This leads to the accumulation of thick mucus and any trapped particles or microorganisms in the airways, decreasing the movement of air and increasing the risk of microbial growth. A smoker’s cough is an attempt to expel this thick mucus out of the respiratory tract. Lower respiratory tract infections are more common in smokers and in those exposed to second-hand smoke, especially infants and children.

Clinical indications of upper respiratory tract infections depend on the infection site as well as the microorganism responsible for the infection. All clinical manifestations result from the inflammatory processes and any direct damage the microorganism inflicts. Clinical manifestations include:

Pneumonia, an acute infection of the lung tissue by a microorganism, is a lower respiratory tract infection. Most pneumonias are bacterial in origin, occurring as a primary condition or secondary to a previous viral infection. Pneumonia is classified as community acquired (CAP) when it occurs outside a health care facility or in someone other than a health care provider. It is more prevalent in smokers and has a much higher incidence in the winter months. Pneumonia diagnosed at least 48 hours after being admitted to a health care facility is referred to as hospital-acquired (or nosocomial) pneumonia and has a mortality rate of up to 50%. Almost 90% is bacterial in nature.

The most common cause of bacterial pneumonia is the gram-positive bacterium Streptococcus pneumoniae, which is responsible for pneumococcal pneumonia. The bacteria Staphylococcus aureus and group A beta-hemolytic streptococci are also frequent causes of pneumonia, as is Pseudomonas aeruginosa. Other pneumonias are caused directly by viruses, such as that seen occasionally with influenza. Young children especially are susceptible to viral pneumonia, usually from infection with respiratory syncytial virus (RSV), parainfluenza, adenovirus, or rhinovirus. Mycoplasmal pneumonia, a relatively common pneumonia, is caused by a microorganism that is, in some respects, between a virus and a bacterium. Individuals who have acquired immunodeficiency syndrome (AIDS) frequently develop an otherwise rare pneumonia called Pneumocystis carinii pneumonia. Individuals exposed to aerosols of previously standing water, for instance, from air-conditioning units or dirty humidifiers, may develop Legionella pneumonia. Finally, individuals who aspirate stomach contents after vomiting or who aspirate water in an experience of near-drowning may develop aspiration pneumonia. For these individuals, the aspirated material itself rather than a microorganism may cause pneumonia by stimulating an inflammatory reaction. Subsequent bacterial infection may also develop.

The risks of developing the pneumonias described above are greater for the young, the old, or for anyone immunocompromised or weakened by another disease or disability. Risk of death after pneumonia is also stratified based on age (over 50 or young, especially the newborn) and the presence of coexisting illness such as congestive heart failure, neoplastic disease, or renal disease.

Much of the damage to the lung tissue after successful colonization of the lungs by a microorganism is the result of the usually vigorous immune and inflammatory reaction mounted by the host. In addition, toxins released by the bacteria causing bacterial pneumonia can directly damage cells of the lower respiratory system, including the surfactant-producing type II alveolar cells. Bacterial pneumonia results in the most striking immune and inflammatory response, the course of which has been well described for pneumococcal pneumonia.

For pneumococcal pneumonia, four stages of disease have been described. These four stages are similar for the other types of pneumonia.

Stage 1, called hyperemia, refers to the initial inflammatory response occurring in the area of lung infection. It is characterized by increased blood flow and increased capillary permeability at the site of infection. It occurs as a result of inflammatory mediators released from mast cells after immune cell activation and tissue injury. These components include histamine and prostaglandin. Mast cell degranulation also activates the complement pathway. Complement acts with histamine and prostaglandin to vasodilate the pulmonary vascular smooth muscle, leading to increased blood flow to the area and increased
capillary permeability. This results in movement of plasma exudate into the interstitial space, causing swelling and edema between the capillary and the alveolus. Fluid buildup between the capillary and the alveolus increases the distance over which oxygen and carbon dioxide must diffuse, thereby decreasing the rate of gas diffusion. Because oxygen is less soluble than carbon dioxide, its movement into the blood is most affected, often leading to a decrease in hemoglobin oxygen saturation. During this first stage of pneumonia, infection spreads to neighboring tissue as a result of increased blood flow and breakdown of neighboring alveolar and capillary membranes as the inflammatory processes continue.

Stage 2 is called red hepatization. It occurs when the alveoli fill with red blood cells, exudate, and fibrin, produced by the host as part of the inflammatory reaction.

Stage 3, called gray hepatization, occurs as white blood cells colonize the infected part of the lung. Then, fibrin deposits accumulate throughout the area of injury and phagocytosis of cell debris occurs.

Stage 4, called the resolution stage, occurs when the inflammatory and immune responses wane; cell debris, fibrin, and bacteria are digested; and macrophages, the cleanup cells of the inflammatory reaction, dominate.

Symptoms are similar for all types of pneumonia but are usually most pronounced for those of bacterial origin.