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Mason: Murra and Nadel's Te tbook of Respirator Medicine, 5th ed.

Copyright 2010 Saunders, An Imprint of Elsevier

MECHANISMS OF HYPOXEMIC RESPIRATORY FAILURE

There are five pathophysiologic mechanisms of hypoxemia: (1) decreased inspired oxygen pressure (PIO2) or fraction, (2) hypoventilation, (3) impaired diffusion, (4) shunt, and (5) ventilation-perfusion (V/Q) mismatch. [5]

Decreased Inspired O

gen Pressure

The PIO2 depends on the FIO2 multiplied by the difference between the Patm and the pressure of saturated vapor (PH 2O): As mentioned previously, the FIO2 at room air is 0.21 and can

decrease only in rare circumstances, such as the saturation of a closed environment with toxic fumes, where the inspired gas mixture contains a lower oxygen fraction. Therefore, according to the equation, a naturally occurring lower PIO2 can be observed only in conditions of low Patm. Patm progressively declines as altitude increases, going from 760 mm Hg at sea level to 253 mm Hg at the summit of Mount Everest (8848 m [29,029 ft]). Hence, PIO2 ranges from 150 mm Hg at sea level ((0.21 ? (760 mm Hg 47 mm Hg)) to 43 mm Hg on top of Mount Everest (0.21 ? (253 mm Hg 47 mm Hg)) (Fig. 91-3). [5a]

FIGURE 91-3

Altitude effects on the pressure of inspired oxygen (PIO2), w hich geographically can range from 43 mm Hg at the summit

of Mount Everest to 158 mm Hg at the Dead Sea. Most major w orld cities are located near sea level, w here the PIO2 is 150 mm Hg.

According to the alveolar gas equation (see earlier), a reduction in PIO2 results in a decrease in PAO2, which consequently reduces the driving pressure for oxygen through the alveolar-capillary membrane, inducing respiratory hypoxemia.

H poventilation

H poventilation
Hypoventilation is the condition defined by the reduction of alveolar ventilation ( PACO2 (PACO2 = K ? /VA, where K is a constant and on the metabolic rate). According to the alveolar gas equation: if the respiratory exchange ratio (R, normally = 0.8) remains constant, any increase in PACO2 results in a reduction of PAO2, which can lead, in severe cases of hypercapnia, to hypoxemia. For example, if the PaCO2 is increased to 80 mm Hg, the resulting PAO2 on room air (at sea level) would be decreased to 50 mm Hg. This form of hypoxemia, exclusively due to hypoventilation, is readily recognizable because it is characterized by a normal (A a)PO2 difference, and a high PaCO2, and is easily corrected by increasing the FIO2 or reducing the PACO2 by increasing alveolar ventilation (e.g., with mechanical ventilation). The reduction of alveolar ventilation leading to an increase in PaCO2 is the result of an imbalance between the function of the respiratory pump and the load applied to the respiratory system. The respiratory pump encompasses all of the neuromuscular structures from the central nervous system to the respiratory muscles, including the motor-neuron and the neuromuscular junction, responsible for the expansion of the chest during inspiration. The respiratory load can be subclassified as the resistive load (due to the resistance of the airways), elastic load (due to the compliance of the lungs and chest wall), and the CO2 production load, determined by the metabolic demands of peripheral tissue, which can increase dramatically during exercise, sepsis, trauma, and other factors. ), which is a determinant of

is the rate of production of CO2, and depends

Impaired Diffusion
Alveolar oxygen must diffuse through the alveolar-endothelial membranes in order to dissolve in the bloodstream and bind to Hb in red blood cells. Under normal conditions, complete oxygenation of blood in the pulmonary capillaries requires only 0.25 second, which is only a third of the total time in which the blood remains in contact with the alveolar-endothelial membrane (Fig. 91-4). Consequently, the relatively long alveolar capillary transit time can compensate for any impairment in oxygen diffusion. Thickening of the blood-gas barrier occurs in several diseases such as diffuse interstitial fibrosis, idiopathic pulmonary fibrosis, cryptogenic organizing pneumonia, asbestosis exposure, ARDS. Nevertheless, owing to this reserve of diffusion time, hypoxemia due solely to impaired diffusion is rarely observed in resting conditions, even during disease states. Impairment in oxygen diffusion through the bloodgas barrier can become clinically significant during exercise or other circumstances causing increased cardiac output, which induces a faster transition of the red cells through the alveolar capillaries. Therefore, rises in cardiac output will increase the flow through the pulmonary capillaries, thereby significantly reducing the time available for oxygen diffusion, which, if combined with an impaired diffusion rate, can lead to the development of hypoxemic respiratory failure because of a diffusion limitation (see Fig. 91-4).

FIGURE 91-4

Oxygen diffusion at the alveolar-capillary barrier requires only a third of the available time to obtain complete equilibration

FIGURE 91-4 Oxygen diffusion at the alveolar-capillary barrier requires only a third of the available time to obtain complete equilibration under normal resting conditions (blue line). Small impairments in diffusion (dashed bro n line) use the available reserve time, maintaining capillary oxygenation of greater than 60 mm Hg, so this impairment w ill be clinically insignificant. Larger diffusion impairments (dashed pale line) may prevent complete oxygenation, w hich during exercise w hen blood flow is increased may become clinically significant, leading to hypoxemic respiratory failure.

Sh n
Shunt is defined as the passage of venous blood into the arterial circulation without passing ventilated alveoli and, consequently, not becoming oxygenated. It is more accurate to define this mechanism as right-to-left shunt, because the communication between the venous and the arterial circulation can cause hypoxemia only if the direction of the shunted blood flow is right to left. Hypoxemic respiratory failure can be caused by intrapulmonary or extrapulmonary shunts. Examples of diseases with intrapulmonary shunts are pulmonary arteriovenous malformations, hepatopulmonary syndrome, and diseases characterized by alveolar consolidation or collapse (e.g., pneumonia, atelectasis). This latter condition of alveolar consolidation or collapse can also be viewed as an extreme V/Q mismatch, defined by areas of the lung that are unventilated but still perfused (discussed later). An interesting clinical example of intrapulmonary shunt is hepatopulmonary syndrome, which is cause by a regional dilation of pulmonary capillaries at the bases of the lungs. In this condition, the shunt increases when the patient is in the upright position, leading to hypoxemia. Because perfusion is redistributed toward the apex of the lung when the patient is placed in the supine position, this positioning will allow progressive reduction of shunt, thereby lessening the hypoxemia. Extrapulmonary shunts are caused by the presence of intracardiac communication between the ventricles or the atria, due to atrial or ventricular septal defects, or by patency of the ductus arteriosus. The presence of hypoxemia caused by shunt is characterized by the failure of PaO2 to rise despite inhalation of pure oxygen (100%). The shunt fraction can be estimated by the following equation: where, is the shunt flow, is the total blood

flow, Cc O2 is the end-capillary O2 content, calculated from the PAO2, CaO2 is the arterial O2 content and is the mixed venous O2 content, measured from the venous blood sampled through the pulmonary artery catheter.

Ven ila ion-Pe f

ion Mi ma ch

To become fully oxygenated and allow the total removal of CO2, all the blood perfusing the lungs needs to be in contact with ventilated alveolar units. Ideally, the V/Q ratio should be equal to 1. Physiologically, in the upright position, the perfusion of the lungs changes anatomically, increasing from the apex to the base, due to either gravitational or anatomic considerations. Likewise, the ventilation is greater at the base of the lung, as opposed to the apical regions. However, from apex to base, the perfusion increases more rapidly than that of ventilation, resulting in a progressive decrease of V/Q ratio. The overall V/Q ratio of the lungs is normally around 0.8. This mild difference of the real V/Q from the ideal value of 1 is responsible for a physiologically appreciable (A a)PO2 difference. V/Q varies broadly between pathophysiologic extremes. On one side, there are alveolar units with no ventilation but normal perfusion, resulting in a V/Q ratio of 0. This phenomenon is referred to as right-to-left shunt, as discussed previously. In these alveolar units, the oxygen content is similar to that of the mixed venous blood and the CO2 is elevated. At the other extreme, some alveolar units are fully ventilated but not perfused, resulting in an infinite V/Q ratio. This area of ventilation is called dead space, in which the alveolar oxygen content is similar to that of the inspired gas mixture and the CO2 is almost absent (Fig. 91-5).

FIGURE 91-5 Ventilation-perfusion (V/Q) ratio displays the normal balance ( a ) betw een alveolar ventilation and vascular perfusion allow ing for proper oxygenation. When ventilation is reduced, the V/Q ratio decreases, in the most extreme case resulting in pure shunt, w here V/Q = 0. When perfusion is reduced, the V/Q ratio increases, in the most extreme case resulting in pure dead space, w here V/Q = infinite ().

Between these two extremes, any alteration of V/Q matching can lead to severe impairments in gas exchange with clinically significant hypoxemia, hypercapnia, or a combination of both. In the majority of respiratory failure cases, V/Q mismatch is the cause of hypoxemia and can be identified by an increased (A a)PO2 difference and exclusion of the other four mechanisms of hypoxemia. Moreover, arterial oxygenation can normally be improved by adding supplemental O2 to the mixture of inspired gas, which increases PAO2 in poorly ventilated alveolar units. Overall, among all five pathophysiologic mechanisms causing hypoxemia, shunt and V/Q mismatch are the most relevant from a clinical perspective. In fact, reduction of PIO2 and impaired diffusion are rarely significant, and hypoventilation-induced hypoxemia can be easily corrected with minimal increments of FIO2. However, in clinical practice, more than one mechanism often contributes at the same time to the development of hypoxemia. It is important to stress that adequate cardiac output is necessary to avoid hypoxemia, because a reduced cardiac output is associated with lung perfusion impairment and consequent inequality of the V/Q ratio. Moreover, a low cardiac output is associated with a significant reduction in mixed venous oxygen saturation, which can thereby cause other mechanisms of hypoxemia (i.e., impaired diffusion), which under normal conditions are clinically insignificant, to contribute to the development of hypoxemia.

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