Chapter 2 Pulmonology

Jessica M. Intravia, MHA, Thomas A. Brown, MD, Sonali J. Shah

Insider’s Guide to Pulmonology for the USMLE Step 1

Pulmonology is a favorite subject for Step 1 because it provides a lot of opportunity to integrate across disciplines. Therefore, you should expect to find pulmonology questions on related subjects such as microbiology, cardiology, and clinical anatomy (we especially recommend spending some time with an anatomy atlas to refamiliarize yourself with chest x-ray films). However, this does not mean that USMLE test makers will forget to include questions regarding pulmonary physiology and pathology. In fact, many pulmonology questions on Step 1 will require you to apply conceptual knowledge of pathophysiology. In other words, avoid memorizing a ton of detailed information for this subject. Instead, focus on reasoning through the pathophysiology of various conditions as they relate to the lung (e.g., why compliance increases with emphysema, why altitude changes alter pH, why certain diseases alter AaDO₂). You will notice that the key point is to constantly ask yourself “why?” when studying for this subject!

Basic concepts—mechanics of breathing

1 What are the driving forces for the following:

A. Inspiratory airflow?

A negative intrapleural pressure (i.e., the pressure outside the lungs) is created by the opposing tendencies of the chest wall to expand and the lung to collapse. This negative intrapleural pressure is transmitted to the alveoli such that there is a pressure gradient between alveolar air spaces and the external environment, resulting in airflow into the lung.

Muscles involved in forced inspiration include the diaphragm, external intercostals, innermost intercostals, and scalene and sternocleidomastoid muscles.

B. Expiratory airflow?

An increase in intrapleural pressure (i.e., becomes less negative) is created by relaxation of the diaphragm and elastic recoil of the lungs and chest wall. Contraction of the abdominal muscles (rectus abdominis, internal and external obliques, transversus abdominis) during forced expiration can also increase the intrapleural pressure. The internal intercostals are also involved in forced expiration.

2 What are the forces of resistance for the following:

A. Inspiratory airflow

Airway resistance, compliance resistance, and tissue resistance are the forces of resistance for inspiration; collectively, these forces determine the overall work of breathing.

Airway resistance is generated by the friction between rapidly moving air molecules and the walls of the airways. It is typically a small component of the work of breathing. Airway resistance is greater in the large airways because they are arranged in series, whereas the small airways are arranged in parallel.

The total resistance (R_T) of a specific number (n) of resistors in series is equal to the sum of their individual resistances such that

By contrast, the total resistance (R_T) of a specific number (n) of resistors in parallel is calculated as

Compliance resistance is generated as the lungs inflate and overcome the intrinsic elastic recoil of the lungs. The work to overcome this resistance (compliance work) normally accounts for the largest proportion of the work of breathing. Note that compliance work is reduced in obstructive lung disease and increased in restrictive lung disease.

Tissue resistance is generated as the pleural surfaces slide over each other during respiration. This resistance is normally minimal because of the presence of pleural fluid. Note that tissue resistance can increase markedly in conditions in which the pleural surfaces become adherent to each other, as may occur with an empyema (Fig. 2-1).

B. Expiratory airflow

Figure 2-1 Relative contributions of the three types of resistance to the total work of breathing.

(From Brown TA: Rapid Review Physiology. Philadelphia, Mosby, 2007.)

Reduction in airway diameter associated with increased intrathoracic pressures affect resistance during expiration. Expiration is typically a passive process because this resistance is small and is easily overcome by the energy provided by elastic recoil of the lung and chest wall. However, in certain conditions in which airway diameter is pathologically reduced (e.g., asthma) or the forces of elastic recoil of the lung are reduced (e.g., emphysema), expiration may become an active process requiring use of accessory muscles.

3 What does pulmonary compliance measure?

Compliance is a measure of lung distensibility. Compliant lungs are easy to distend. Compliance (C) can be measured as the change in volume (ΔV) required for a fractional change in pressure (ΔP):

The properties of compliance and elastance (tendency of the lung to recoil inward; see question 5) are inversely proportional to one another. In conditions in which elastance decreases (e.g., emphysema), compliance will automatically increase.

4 With respect to the compliance curve of the lungs, how might breathing at an elevated functional residual capacity in chronic obstructive pulmonary disease result in less “efficient” breathing?

Figure 2-2 shows a compliance curve of the lungs. Note that the lungs are most compliant in the midportion of the inspiratory curve (steepest slope). Breathing at an elevated functional residual capacity (as patients with chronic obstructive pulmonary disease [COPD] are prone to do for a variety of reasons) is less efficient and requires more work.

Figure 2-2 Compliance curve of the lungs: lung volume plotted against changes in transpulmonary pressure (the difference between pleural and alveolar pressure).

(From Brown TA: Rapid Review Physiology. Philadelphia, Mosby, 2007.)

5 What does pulmonary elastance measure? How is pulmonary elastance altered in restrictive and obstructive lung diseases and why?

Elasticity is the property of matter that makes it resist deformation. As elasticity increases, increasingly greater pressure changes will be required to distend the lungs. Pulmonary elastance (E) can be calculated as the change in pressure (ΔP) divided by the change in volume (ΔV):

In restrictive lung diseases such as silicosis and asbestosis, which are characterized by parenchymal fibrosis, pulmonary elastance increases. In COPD, which is characterized by parenchymal destruction, elastance decreases.

6 How does surfactant affect alveolar surface tension?

Water molecules lining the surface of alveoli are attracted to each other and are repelled by the hydrophobic air molecules. The attractive force between water molecules generates surface tension, which in turn produces a collapsing pressure that promotes alveolar collapse. Surfactant is composed of phospholipids (mainly lecithin and sphingomyelin) that reduce the collapsing pressure by minimizing the interaction between alveolar fluid and alveolar air (Fig. 2-3).

Figure 2-3 Role of surfactant in reducing alveolar surface tension. Note the orientation of the hydrophilic “head” in the alveolar fluid and the hydrophobic “tail” in the alveolar air.

(From Brown TA: Rapid Review Physiology. Philadelphia, Mosby, 2007.)

7 Why are smaller alveoli more prone to collapse, and how is this relevant to neonatal respiratory distress syndrome?

Laplace’s law states that the collapsing pressure (P) is directly proportional to surface tension (T) and inversely proportional to the alveolar radius (R), such that smaller alveoli will experience a larger collapsing pressure:

The combination of small alveoli and inadequate surfactant production in premature infants contributes to respiratory failure in the neonatal respiratory distress syndrome.

Fetal amniotic fluid can be measured for lecithin and sphingomyelin content, the ratio of which can serve as an indicator of fetal lung maturity. A ratio of <1.5 is a strong predictor of neonatal respiratory distress syndrome. Maternal steroids can be given if the fetus is less than 35 weeks old in order to increase fetal lung maturity before delivery.

8 What is the minute ventilation?

Minute ventilation is the total volume of air that enters and exits the lung each minute. The normal (resting) minute ventilation is a function of tidal volume and respiratory rate:

Example:

9 What is “dead space”? What is the difference between anatomic dead space and physiologic dead space?

Dead space refers to lung volume that is ventilated but not perfused by deoxygenated blood, such that there is no potential for gas exchange in this space. The anatomic dead space is lung volume that receives ventilation, but in which there are no pulmonary capillaries available for gas exchange. This anatomic dead space includes the nasal cavity, pharynx, larynx, trachea, bronchi, and conducting bronchioles, often referred to as the conducting airways. The physiologic dead space includes both the anatomic dead space and the alveoli that are ventilated but not perfused (alveolar dead space), so no gas exchange occurs in them either.

The majority of physiologic dead space can be attributed to the apex of the lung due to poor perfusion at the apex compared with the base. Exercise decreases physiologic dead space by improving perfusion to the entire lung.

Basic concepts—ventilation-perfusion matching

11 What does the ventilation/perfusion ratio measure, and what is its approximate value? What is an “ideal” value for this ratio?

The ventilation/perfusion ratio (/) measures how well pulmonary perfusion and pulmonary ventilation are matched, indicating how efficiently oxygenation of blood is occurring in the pulmonary capillaries. Normally, the lungs receive close to the entire cardiac output (~5 L/min), and the prototypical 70-kg man has an alveolar ventilation rate of roughly 4 L/min (as shown in question 10). A ventilation rate of 4 L/min and a pulmonary perfusion rate of 5 L/min yield a / ratio of 0.8, which implies suboptimal matching of pulmonary ventilation and perfusion. A / ratio of 1 is ideal, and represents optimal matching of pulmonary ventilation and perfusion.

The / ratio can be applied to the lungs as a whole, or to separate areas of the lungs, and is a measure of the efficiency of ventilation in those separate areas as well. Regional differences in ventilation and perfusion exist across various zones of the lungs because of the force of gravity. In an upright subject, both blood flow and perfusion are decreased at the apex of the lung and increased at the base of the lung. However, the decrease in perfusion is greater than the decrease in ventilation at the apex of the lung, leading to an increased / ratio. Likewise, the / ratio at the base is decreased because the increase in perfusion is greater than the increase in ventilation. This difference leads to an apical / ratio of 3, while the basal / ratio is closer to 0.6.

During exercise, the greater increase in alveolar ventilation and lesser increase in cardiac output lead to a more uniform / ratio from apex to base that more closely approximates the ideal / ratio of 1.0.

12 What conditions cause an increase in the / ratio?

The / ratio increases whenever pulmonary ventilation is proportionately greater than pulmonary perfusion. As just discussed, exercise is a normal situation in which ventilation increases proportionally more than perfusion, and in this case it optimizes the / ratio. A pathologic condition that increases the / ratio is a pulmonary embolus. In this condition, patients are often tachypneic (respiring rapidly), which increases ventilation. The clot in the lungs also reduces pulmonary perfusion, so both of these processes increase the / ratio. In fact, the / ratio in the blocked segment would theoretically approach infinity because blood flow to that region is completely blocked ( = 0). The pathologic consequence of an increased / ratio is that ventilation is “wasted” in lung areas that are not adequately perfused.

13 What causes a decrease in the ventilation/perfusion ratio?

Generally, any lung disease in which the process of ventilation itself is compromised will decrease the amount of oxygen that the pulmonary blood flow receives, predisposing the patient to hypoxemia. This is deleterious because less oxygen diffuses into the blood that flows through the lungs. Additionally, less carbon dioxide can be “blown off,” predisposing to hypercapnia. An example is asthma, in which the bronchoconstriction that occurs impairs ventilation and reduces the / ratio.

Patients with decreased / ratio will respond to oxygen administration. However, a / ratio of 0 generally implies an obstructed mainstem bronchus and will not respond to oxygen.

14 What effect does chronic obstructive pulmonary disease usually have on the ventilation-perfusion ratio?

Airway obstruction in COPD can reduce ventilation relative to perfusion, decreasing the / ratio. However, pulmonary capillary loss in COPD can increase ventilation relative to perfusion, causing an increased / ratio. In fact, if these two processes are occurring in the same patient, this patient can have a normal / ratio despite severe ventilation/perfusion mismatches in different parts of the lung!

15 What is the difference between an anatomic shunt and a physiologic shunt?

Most anatomic shunts occur within the heart when deoxygenated blood from the right side of the heart crosses the septum and mixes with oxygenated blood from the left side of the heart. This mixture results in varying degrees of hypoxemia that cannot be improved with the administration of 100% O₂.

In a physiologic shunt, deoxygenated blood bypasses the gas-exchanging unit. Atelectasis can occur in many lung diseases including pneumonia. In atelectasis, ventilatory obstruction to the gas-exchanging unit leads to a subsequent loss of volume and a / ratio of 0.

Basic concepts—gas exchange

16 What influences the diffusion of gases from the alveoli into the pulmonary capillaries, and vice versa?

Gas diffusion across a membrane (the pulmonary membrane in this case) is described by Fick’s law of diffusion:

where V_gas is the volume of gas that traverses the membrane per unit time, A is the surface area of the membrane, D is the diffusivity of the particular gas in the particular membrane, P₁ − P₂ is the partial pressure difference of the specific gas across the membrane, and T is the thickness of the membrane.

It is important to recognize that all pulmonary diseases that create respiratory dysfunction affect one or more of the parameters in the diffusion equation. For example, in asthma, the impaired ventilation reduces the pressure gradient for oxygen across the membrane. In emphysema, ventilation is impaired (reducing the pressure gradient) and the surface area of the pulmonary membrane is reduced from loss of alveoli.

Note: The diffusing capacity of the pulmonary membrane is defined as the volume of gas (typically measured using carbon monoxide) that can diffuse across the pulmonary membrane per mm Hg pressure difference across the membrane. It can be seen from Fick’s law that the diffusing capacity is dependent on the surface area, gas diffusivity, and membrane thickness.

17 What is the alveolar-arterial oxygen gradient and what is the clinical significance of its magnitude?

The alveolar-arterial oxygen gradient (PAO₂ − PAO₂, sometimes designated AaDO₂) is a measure of the difference in oxygen tension, or partial pressure, between the alveoli and arterial blood. In a healthy person, a typical alveolar oxygen tension (PAO₂) might be roughly 110 mm Hg, whereas the arterial oxygen tension (PAO₂) might be roughly 100 mm Hg. In such a healthy person, this slight 10 mm Hg difference in the partial pressure of oxygen between these two “compartments” reflects the highly efficient diffusion of oxygen across the pulmonary membrane. AaDO₂ increases by 3 mm Hg with every decade of life past the age of 30, but should never exceed 25 mm Hg. A high alveolar-arterial oxygen gradient implies the presence of pulmonary disease that is causing impaired diffusion of alveolar oxygen across the pulmonary membrane, resulting in hypoxemia. In contrast, AaDO₂ can appear normal in a patient who is hypoventilating.

18 How is the alveolar-arterial oxygen gradient calculated?

where

where FIO₂ = the fraction of inspired oxygen (usually 0.21), PB is barometric pressure (usually 760 mm Hg), PH₂O is water vapor pressure (usually 47 mm Hg), PACO₂ = alveolar pressure of carbon dioxide, which equals the arterial pressure of carbon dioxide due to rapid diffusion across the alveolar membrane, and R = the respiratory quotient (usually 0.8).

19 What are the primary determinants of respiratory drive?

Respirations do not occur without input from the nervous system, which comes from the medullary respiratory center (or from conscious drive). The respiratory center responds to input from central and peripheral chemoreceptors. Hypoxia, hypercapnia, and acidemia stimulate peripheral chemoreceptors that then transmit to and stimulate the respiratory center to increase the rate and depth of respirations. Central chemoreceptors are stimulated by hypercapnia by way of CO₂ diffusing across the blood-brain barrier and dissolving to form carbonic acid, thereby lowering the pH of the central nervous system (CNS). Central chemoreceptors do not respond directly to hypoxia.

Note: The predominant mechanism of respiratory suppression of the barbiturates, benzodiazepines, opioids, and general anesthetics is to make the medullary respiratory center less responsive to increases in PaCO₂.

20 How does increasing or decreasing the arterial PCO₂ affect pH?

When CO₂ dissolves in water, the following reaction occurs:

where CA is carbonic anhydrase.

If additional CO₂ is added, the reaction shifts to the right, creating more hydrogen ions, which decrease the pH of the solution. Conversely, removal of CO₂ pushes the reaction to the left, resulting in removal of H⁺ from solution, with an overall increase in pH. It is this reaction that the lungs exploit to compensate for alterations in arterial pH.

By increasing or decreasing ventilation, and thereby affecting the arterial PCO₂ levels, the pH can be raised or lowered.

21 What is respiratory acidosis? Respiratory alkalosis?

In respiratory acidosis, the lungs are not ventilating well, and the CO₂ that builds up shifts the equation in question 20 to the right, lowering the pH to an abnormal level. In respiratory alkalosis, the lungs are blowing off too much CO₂, shifting the same equation to the left and raising the pH to an abnormal level. In both cases, the respiratory rate and depth are pathologically mismatched to the physiologic demands/needs.

The kidneys attempt to compensate for respiratory acidosis by retaining bicarbonate, or for respiratory alkalosis by increasing bicarbonate excretion, exploiting the other side of this chemical reaction. Unlike the process of respiratory compensation, renal compensation is slow and can take several days to be complete.

Step 1 Secret

Recognizing various acid-base disorders not only is a USMLE favorite but will be a very useful skill during your clinical years!

22 What are the forced expiratory volume and the FEV₁/FVC ratio?

The forced expiratory volume (FEV₁) is the maximum amount of air that can be expired in 1 second following a full inspiration. The forced vital capacity (FVC) is the total amount expired following a full inspiration. The FEV₁/FVC ratio is therefore the percent volume of air that can be expired in 1 second relative to the maximum expiration.

23 What is the principal difference between “restrictive” and “obstructive” lung disease with respect to the FEV₁/FVC ratio?

In restrictive lung disease (e.g., pulmonary fibrosis), decreased pulmonary compliance limits inspiratory volumes. Although expiration is not impaired, the limited inspiratory volumes result in smaller FEV₁ and FVC volumes. Furthermore, the increased pulmonary elastic recoil results in a smaller decrease in FEV₁ than in FVC, resulting in a normal or modestly increased FEV₁/FVC ratio.

In obstructive lung disease, expiratory airflow is impaired secondary to airway narrowing, and from decreased pulmonary elastic recoil in emphysematous COPD. FEV₁ is decreased proportionally more than FVC, resulting in a reduced FEV₁/FVC ratio.

Table 2-1 lists some examples of obstructive and restrictive lung diseases.

Table 2-1 Obstructive and Restrictive Lung Diseases

Obstructive Lung Diseases	Restrictive Lung Diseases
Chronic bronchitis Emphysema Asthma Bronchiectasis Cystic fibrosis	Neuromuscular diseases (poliomyelitis, myasthenia gravis, Duchenne muscular dystrophy, Guillain-Barré syndrome) Acute respiratory distress syndrome (ARDS) Neonatal respiratory distress syndrome Sarcoidosis Idiopathic pulmonary fibrosis Goodpasture’s syndrome Wegener’s granulomatosis Drug toxicity Pleural diseases