Review of Medical Physiology - William F. Ganong 2002

Respiration
Adaptive changes in respiration in health and disease
Effect of exercise

Numerous cardiovascular and respiratory mechanisms must integrate their activity when physical exertion creates a demand for O₂ in active Tissues, while excess CO₂ and heat are eliminated from the body. Vascular changes increase Blood flow to the Muscles, whereas adequate Circulation is maintained in the rest of the body (see Chapter 33). Furthermore, there is an additional increase in O₂ delivery from the blood to the working muscles during exercise, along with ventilation that ensures the elimination of a certain amount of heat and excess CO₂.

Changes in Ventilation

During exercise, The amount of O₂ entering the blood from the Lungs increases because O₂ is extracted by every unit of blood, and pulmonary blood flow per minute increases. A decrease in blood P_O2 flowing through the pulmonary capillaries from 40 to 25 mmHg or less causes an increase in the alveolar-capillary P_O2 gradient, allowing more O₂ to enter the blood. Concurrently, the blood flow velocity increases from 5.5 to 20–35 L/min or more. As a result, the total amount of O₂ entering the blood increases from 250 mL/min at rest to over 4000 mL/min. The amount of CO₂ eliminated from each unit of blood rises from 200 to 8000 mL/min. The increase in O₂ uptake is proportional to the highest workload. Beyond this point, the level of O₂ consumption plateaus, while blood lactate levels increase (Fig. 37-1). Lactate is released from muscles where aerobic energy store resynthesis cannot keep pace with its utilization, and the oxygen debt of energy begins to increase (see Chapter 3). Fig. 37-2 illustrates the abrupt increase in ventilation at the onset of exercise, which occurs after a brief pause, followed by a more gradual increase thereafter. During moderate exercise, tidal volume increases, accompanied by an increase in respiratory rate as the exertion becomes more vigorous. Cessation of exercise abruptly reduces ventilation after a brief pause back to pre-exercise levels. The sudden increase at THE START OF exercise is thought to be driven by psychological stimuli and afferent impulses from Muscle, ligament, and joint proprioceptors. It is also recognized that the more gradual increase is due to humoral influences, as arterial pH, P_CO2, and P_O2 remain constant during moderate exercise. The increase in ventilation is proportional to the increase in O₂ consumption; however, the mechanisms responsible for respiratory stimulation are still a matter of debate. Elevated body Temperature may also affect respiration. As noted in Chapter 36, exercise increases plasma K⁺ levels, and this increase can stimulate peripheral chemoreceptors. Alternatively, it may result from an increased sensitivity of the respiratory center to CO₂, or from the fact that respiratory fluctuations in arterial P_CO2 are amplified by an increase in mean arterial P_CO2, making CO₂ responsible for the rise in ventilation. O₂ also plays a role, even though arterial P_O2 does not decrease. During physical work, the increase in ventilation during 100% O₂ breathing is 10–20% less than during air breathing (Fig. 37-3). Therefore, the ongoing influence of numerous diverse factors combines to enhance ventilation during moderate exercise.

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Fig. 37-1. Relationship between workload, blood lactate level, and O₂ uptake. I-VI represent workload increments achieved by increasing the speed and elevation of the treadmill during exercise (reproduced with permission from Mitchell JH, Blomqvist G: Maximal oxygen uptake. N Engl J Med 1971;284:1018).

Fig. 37-2. Schematic representation of ventilatory changes during exercise.

As exercise becomes more vigorous, the buffering of lactic acid quantitatively increases, thereby releasing a greater amount of CO₂, which further enhances ventilation. The response to incremental exercise is shown in Fig. 37-4. With increased acid production, ventilation rises, and since CO₂ production is proportional, alveolar and arterial CO₂ changes are relatively small (isocapnic buffering). As hyperventilation ensues, alveolar P_CO2 rises. With further accumulation of lactic acid, the increase in ventilation outpaces CO₂ production, and both alveolar and arterial P_CO2 decrease. The drop in arterial P_CO2 provides respiratory compensation (see Chapter 39) for the metabolic acidosis induced by the added lactic acid. The additional increase in ventilation resulting from acidosis is mediated by the carotid bodies, as this response is absent following their removal.

Fig. 37-3. Effect of 100% O₂ on ventilation during bicycle ergometer exercise at various workloads (reproduced with permission from Astrand P-O: The respiratory activity in man exposed to prolonged Hypoxia. Acta Physiol Scand 1954;30:343).

Post-exercise respiratory rate does not return to baseline until the oxygen debt is repaid, which can take up to 90 minutes. The stimulus for post-exercise ventilation is not arterial P_CO2 (which is typically normal or decreased), but rather an elevated arterial H⁺ concentration resulting from lactacidemia. The magnitude of the oxygen debt quantitatively exceeds the basal O₂ consumption from the cessation of exertion until return to pre-exercise baseline levels. During the repayment of oxygen debt, There is a slight increase in muscle Myoglobin O₂ concentration. ATP and phosphorylcreatine are resynthesized, and lactic acid is cleared. About 80% of lactic acid is converted into Glycogen, and 20% is metabolized into CO₂ and H₂O.

Fig. 37-4. Changes in alveolar P_CO2, alveolar P_O2, ventilation (V_E), CO₂ production (V_CO2), O₂ consumption (V_O2), arterial HCO₃^-, and arterial pH during incremental bicycle ergometer exercise in a normal adult male (reproduced with permission from Wasserman K, Whipp BJ, Casaburi R: Respiratory Control during exercise. In Handbook of Physiology, Section 3: The Respiratory system, Vol. II, part 2, Fishman AP [editor], American Physiological Society, 1986).

Because strenuous exercise generates excess CO₂ from lactic acid buffering, the respiratory exchange ratio (RER) rises to 1.5–2.0. Following exercise, once the oxygen debt has been repaid, the RER drops to 0.5 or lower.

Changes in Tissues

During exercise, maximal O₂ uptake is limited by the maximal rate of O₂ transport to the Cell/35.html">Mitochondria of the active muscles. Furthermore, this limitation is normally independent of any impairment in pulmonary O₂ uptake, and arterial blood Hemoglobin remains fully saturated even during the most strenuous exertion.

During exercise, contracting muscles utilize more O₂; consequently, tissue P_O2 and venous blood P_O2 in the active muscles drop almost to zero. More O₂ diffuses out of the blood, the P_O2 of the blood supplying the muscles decreases, and greater amounts of O₂ are released from oxyhemoglobin. Because capillaries in contracting muscles dilate and numerous previously closed capillaries open up, the average distance from the vascular bed to the tissue Cells is significantly reduced. This facilitates the movement of O₂ from the blood to the cells. The oxyhemoglobin dissociation curve steepens at P_O2 values below 60 mmHg, providing a relatively large amount of O₂ for every 1 mmHg drop in P_O2 (see Fig. 35-2). The supply of additional O₂ is promoted by the accumulation of CO₂ and rising temperature in active tissues; this likely increases 2,3-DPG in erythrocytes, shifting the dissociation curve to the right (see Fig. 35-3). The net effect is a threefold increase in O₂ extraction from each unit of blood. Combined with a thirtyfold or greater increase in blood flow, this elevates the metabolic rate in muscles up to 100-fold during exercise (see Chapter 3).

Fatigue

Fatigue is a complex phenomenon resulting from intense physical exertion or mental effort, and it is also a symptom of many diverse diseases. During exercise, acidosis and other factors contribute to the onset of fatigue. Under these conditions, exertion becomes difficult, and there is a subjective loss of strength that correlates with the level of O₂ uptake rather than actual work performed expressed in kg·m/min. Impulses blocked in the afferent pathways from muscle proprioceptors create a sensation of "exhaustion." The effects of acidosis on the Brain may also be responsible for the feeling of fatigue. Prolonged exertion induces hypoglycemia in normal individuals, although preventing hypoglycemia does not affect endurance or delay the onset of exhaustion. On the other hand, in humans, there is a correlation between exhaustion and the degree of muscle glycogen depletion as determined by muscle biopsy. Sustained muscle contractions become painful because the muscles are ischemic and substances that stimulate pain endings (P factor; see Chapter 7) accumulate. Rhythmic contractions, however, are not painful because the P factor is continuously washed out. Muscle stiffness may develop due to the accumulation of interstitial fluid in muscles during exertion.

Heat dissipation during exercise is described in Chapter 33 and illustrated in Fig. 33-4, while changes in acid-base balance associated with respiration are covered in Chapter 39.