Harrison’s Manual of Medicine



Disturbances of Respiratory Function
Diagnostic Procedures

Disturbances of Respiratory Function
The respiratory system includes not only the lungs but also the CNS, chest wall (diaphragm, abdomen, intercostal muscles), and pulmonary circulation. Prime function of the system is to exchange gas between inspired air and venous blood.
DISTURBANCES IN VENTILATORY FUNCTION   (Fig. 127-1 and Fig. 127-2)   Ventilation is the process whereby lungs deliver fresh air to alveoli. Measurements of ventilatory function consist of quantification of air in the lungs [total lung capacity (TLC), residual volume (RV)] and the rate at which air can be expelled from the lungs [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1)] during a forced exhalation from TLC. Expiratory flow rates may be plotted against lung volumes yielding a flow-volume curve (HPIM-15, Fig. 250-4, p. 1448).

FIGURE 127-1. Lung volumes, shown by block diagrams (left) and by a spirographic tracing (right). TLC, total lung capacity; VC, vital capacity; RV, residual volume; IC, inspiratory capacity; ERV, expiratory reserve volume; FRC, functional residual capacity; VT, tidal volume. (From SE Weinberger, JM Drazen: HPIM-15, 1447.)

FIGURE 127-2. Flow diagram outlining the diagnostic approach to the pt with hypoxemia (PaO2 <80 mmHg). PAO2 – PaO2 is usually <15 mmHg for subjects £30 years old, and increases ~3 mmHg per decade after age 30.

Two major patterns of abnormal ventilatory function are restrictive and obstructive patterns (Table 127-1 and Table 127-2).

Table 127-1 Common Respiratory Diseases by Diagnostic Categories

Table 127-2 Alterations in Ventilatory Function

In obstructive pattern:

Hallmark is decrease in expiratory flow rate, i.e., FEV1.

Ratio FEV1/FVC is reduced.

TLC is normal or increased.

RV is elevated due to trapping of air during expiration.
In restrictive disease:

Hallmark is decrease in TLC.

May be caused by pulmonary parenchymal disease or extraparenchymal (neuromuscular such as myasthenia gravis or chest wall such as kyphoscoliosis).

Pulmonary parenchymal disease usually occurs with a reduced RV, but extraparenchymal disease (with expiratory dysfunction) occurs with an increased RV.
DISTURBANCES IN PULMONARY CIRCULATION   Pulmonary vasculature transmits the RV output, ~5 L/min at a low pressure. Perfusion of lung greatest in dependent portion. Assessment requires measuring pulmonary vascular pressures and cardiac output to derive pulmonary vascular resistance. Pulmonary vascular resistance rises with hypoxia, intraluminal thrombi, scarring, or loss of alveolar beds.
All diseases of the respiratory system causing hypoxia are capable of causing pulmonary hypertension. However, pts with hypoxemia due to chronic obstructive lung disease, interstitial lung disease, chest wall disease, and obesity-hypoventilation–sleep apnea are particularly likely to develop pulmonary hypertension.
DISTURBANCES IN GAS EXCHANGE   Primary functions of the respiratory system are to remove CO2 and provide O2. Normal tidal volume is about 500 mL, and normal frequency is 15 breaths per minute for a total ventilation of 7.5 L/min. Because of dead space, alveolar ventilation is 5 L/min.
Partial pressure of CO2 in arterial blood (PaCO2) is directly proportional to amount of CO2 produced each minute (
CO2) and inversely proportional to alveolar ventilation (

Gas exchange is critically dependent on proper matching of ventilation and perfusion.
Assessment of gas exchange requires measurement of ABGs. The actual content of O2 in blood is determined by both PO2 and hemoglobin.
Arterial PO2 can be used to measure alveolar-arterial O2 difference (A–a gradient). Increased A–a gradient (normal <15 mmHg, rising by 3 mmHg each decade after age 30) indicates impaired gas exchange.
In order to calculate A–a gradient, the alveolar PO2 (PAO2) must be calculated:

where FIO2 = fractional concentration of inspired O2 (0.21 breathing room air), PB = barometric pressure (760 mmHg at sea level), PH2O = water vapor pressure (47 mmHg when air is saturated at 37°C), and R = respiratory quotient (the ratio of CO2 production to O2 consumption, usually assumed to be 0.8).
Adequacy of CO2 removal is reflected in the partial pressure of CO2 in arterial blood.
Because measurement of ABGs necessitates arterial puncture, noninvasive techniques may be useful, particularly to determine trends in gas exchange over time. The pulse oximeter measures oxygen saturation SaO2 rather than PaO2. While widely used, clinicians must be aware that (1) the relationship between SaO2 and PaO2 is curvilinear, flattening above a PaO2 of 60 mmHg; (2) poor peripheral perfusion may interfere with the oximeter’s function; and (3) the oximeter provides no information about PCO2.
Ability of gas to diffuse across the alveolar-capillary membrane is assessed by the diffusing capacity of the lung (DLCO). Carried out with low concentration of carbon monoxide during a single 10-s breath-holding period or during 1 min of steady breathing. Value depends on alveolar-capillary surface area, pulmonary capillary blood volume, degree of ventilation-perfusion (
) mismatching, and thickness of alveolar-capillary membrane.
MECHANISMS OF ABNORMAL FUNCTION   Four basic mechanisms of hypoxemia are (1) ¯ inspired PO2, (2) hypoventilation, (3) shunt, and (4)
mismatch. Diffusion block contributes to hypoxemia only under selected circumstances. Approach to the hypoxemic pt is shown in Fig. 127-2.
The essential mechanism underlying all cases of hypercapnia is inadequate alveolar ventilation. Potential contributing factors include (1) increased CO2 production, (2) decreased ventilatory drive, (3) malfunction of the respiratory pump or increased airways resistance, and (4) inefficiency of gas exchange (increased dead space or
mismatch) necessitating a compensatory increase in overall minute ventilation.
Diagnostic Procedures
NONINVASIVE PROCEDURES   Radiography   No CXR pattern is sufficiently specific to establish a diagnosis; instead, the CXR serves to detect disease, assess magnitude, and guide further diagnostic investigation. Thoracic CT is now routine in evaluation of pts with pulmonary nodules and masses. CT is especially helpful in the assessment of pleural lesions. Contrast enhancement also makes thoracic CT useful in differentiating tissue masses from vascular structures. High-resolution CT has largely replaced bronchography in the evaluation of surgical bronchiectasis and is useful in evaluation of pts with interstitial lung disease. Spiral or helical CT is increasingly used in the diagnosis of pulmonary thromboembolism. MRI is generally less useful than CT but is preferred in evaluation of abnormalities at the lung apex, adjacent to the spine, and at the thoracoabdominal junction.
Skin Tests   Specific skin test antigens are available for tuberculosis, histoplasmosis, coccidioidomycosis, blastomycosis, trichinosis, toxoplasmosis, and aspergillosis. A positive delayed reaction (type IV) to a tuberculin test indicates only prior infection, not active disease. Immediate (type I) and late (type III) dermal hypersensitivity to Aspergillus antigen supports diagnosis of allergic bronchopulmonary aspergillosis in pts with a compatible clinical illness.
Sputum Exam   Sputum is distinguished from saliva by presence of bronchial epithelial cells and alveolar macrophages. Sputum exam should include gross inspection for blood, color, and odor, as well as microscopic inspection of carefully stained smears. Culture of expectorated sputum may be misleading owing to contamination with oropharyngeal flora. Sputum samples induced by inhalation of nebulized, warm, hypertonic saline can be stained using immunofluorescent techniques for the presence of Pneumocystis carinii.
Pulmonary Function Tests   May indicate abnormalities of airway function, alterations of lung volume, and disturbances of gas exchange. Specific patterns of pulmonary function may assist in differential diagnosis. PFTs may also provide objective measures of therapeutic response, e.g., to bronchodilators.
Pulmonary Scintigraphy   Scans of pulmonary ventilation and perfusion aid in the diagnosis of pulmonary embolism. Quantitative ventilation-perfusion scans are also used to assess surgical resectability of lung cancer in pts with diminished respiratory function. Gallium scanning may be used to identify inflammatory disease of the lungs or mediastinal lymph nodes. Inflammatory activity of the lungs detected with gallium may be associated with diffuse interstitial infections. Gallium uptake by the lungs may also occur in P. carinii pneumonia (PCP).
INVASIVE PROCEDURES   Bronchoscopy   Permits visualization of airways, identification of endobronchial abnormalities, and collection of diagnostic specimens by lavage, brushing, or biopsy. The fiberoptic bronchoscope permits exam of smaller, more peripheral airways than the rigid bronchoscope, but the latter permits greater control of the airways and provides more effective suctioning. These features make rigid bronchoscopy particularly useful in pts with central obstructing tumors, foreign bodies, or massive hemoptysis. The fiberoptic bronchoscope increases the diagnostic potential of bronchoscopy, permitting biopsy of peripheral nodules and diffuse infiltrative diseases as well as aspiration and lavage of airways and airspaces. Fiberoptic biopsy is particularly useful in diagnosing diffuse infectious processes, lymphangitic spread of cancer, and granulomatous diseases.
Video-Assisted Thoracic Surgery   Now commonly used for diagnosis of pleural lesions as well as peripheral parenchymal infiltrates and nodules. Has largely replaced “open biopsy”; may be used therapeutically.
Percutaneous Needle Aspiration of the Lung   Usually performed under CT guidance to obtain cytologic or microbiologic specimens from local pulmonary lesions.
Bronchoalveolar Lavage (BAL)   An adjunct to fiberoptic bronchoscopy permitting collection of cells and liquid from distal air spaces. Useful in diagnosis of PCP, other infections, and some interstitial diseases.
Thoracentesis and Pleural Biopsy   Thoracentesis should be performed as an early step in the evaluation of any pleural effusion of uncertain etiology. Analysis of pleural fluid helps differentiate transudate from exudate (Chap. 134). (Exudate: pleural fluid LDH >200 IU, pleural fluid/serum protein >0.5, pleural fluid/serum LDH >0.6.) Pleural fluid pH <7.2 suggests that an exudate associated with an infection is an empyema and will almost certainly require drainage. WBC count and differential; glucose, PCO2, amylase, Gram stain, culture, and cytologic exam should be performed on all specimens. Rheumatoid factor and complement may also be useful. Closed pleural biopsy can also be done when a pleural effusion is present, but has largely been replaced by video- assisted thoracoscopy.
Pulmonary Angiography   The definitive test for pulmonary embolism; may also reveal AV malformations.
Mediastinoscopy   Diagnostic procedure of choice in pts with disease involving mediastinal lymph nodes. However, lymph nodes in left superior mediastinum must be approached via mediastinotomy.

For a more detailed discussion, see Weinberger SE, Drazen JM: Disturbances of Respiratory Function, Chap. 250, p. 1446, and Diagnostic Procedures in Respiratory Diseases, Chap. 251, p. 1453, in HPIM-15.


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