636 SECTION VIIRespiratory Physiology
more gradual decline to pre-exercise values. The abrupt
increase at the start of exercise is presumably due to psychic
stimuli and afferent impulses from proprioceptors in muscles,
tendons, and joints. The more gradual increase is presumably
humoral, even though arterial pH, PCO 2 , and PO 2 remain con-
stant during moderate exercise. The increase in ventilation is
proportional to the increase in O 2 consumption, but the mech-
anisms responsible for the stimulation of respiration are still
the subject of much debate. The increase in body temperature
may play a role. Exercise increases the plasma K+ level, and
this increase may stimulate the peripheral chemoreceptors. In
addition, it may be that the sensitivity of the neurons control-
ling the response to CO 2 is increased or that the respiratory
fluctuations in arterial PCO 2 increase so that, even though the
mean arterial PCO 2 does not rise, it is CO 2 that is responsible
for the increase in ventilation. O 2 also seems to play some role,
despite the lack of a decrease in arterial PO 2 , since during the
performance of a given amount of work, the increase in venti-
lation while breathing 100% O 2 is 10–20% less than the
increase while breathing air. Thus, it currently appears that a
number of different factors combine to produce the increase in
ventilation seen during moderate exercise.
When exercise becomes more vigorous, buffering of the
increased amounts of lactic acid that are produced liberates
more CO 2 , and this further increases ventilation. The
response to graded exercise is shown in Figure 37–15. With
increased production of acid, the increases in ventilation and
CO 2 production remain proportional, so alveolar and arterial
CO 2 change relatively little (isocapnic buffering). Because of
the hyperventilation, alveolar PO 2 increases. With further
accumulation of lactic acid, the increase in ventilation out-
strips CO 2 production and alveolar PCO 2 falls, as does arterial
PCO 2. The decline in arterial PCO 2 provides respiratory com-
pensation for the metabolic acidosis produced by the addi-
tional lactic acid. The additional increase in ventilation
produced by the acidosis is dependent on the carotid bodies
and does not occur if they are removed.
The respiratory rate after exercise does not reach basal
levels until the O 2 debt is repaid. This may take as long as 90
min. The stimulus to ventilation after exercise is not the arte-
rial PCO 2 , which is normal or low, or the arterial PO 2 , which is
normal or high, but the elevated arterial H+ concentration
due to the lactic acidemia. The magnitude of the O 2 debt is
the amount by which O 2 consumption exceeds basal con-
sumption from the end of exertion until the O 2 consumption
has returned to pre-exercise basal levels. During repayment of
the O 2 debt, the O 2 concentration in muscle myoglobin rises
slightly. ATP and phosphorylcreatine are resynthesized, and
lactic acid is removed. Eighty percent of the lactic acid is con-
verted to glycogen and 20% is metabolized to CO 2 and H 2 O.
Because of the extra CO 2 produced by the buffering of lac-
tic acid during strenuous exercise, the ratio of CO 2 to O 2 (res-
piratory exchange ratio; R) rises, reaching 1.5 to 2.0. After
exertion, while the O 2 debt is being repaid, the R falls to 0.5 or
less.
CHANGES IN THE TISSUES
Maximum O 2 uptake during exercise is limited by the maxi-
mum rate at which O 2 is transported to the mitochondria in the
exercising muscle. However, this limitation is not normally due
to deficient O 2 uptake in the lungs, and hemoglobin in arterial
blood is saturated even during the most severe exercise.
During exercise, the contracting muscles use more O 2 , and
the tissue PO 2 and the PO 2 in venous blood from exercising
muscle fall nearly to zero. More O 2 diffuses from the blood,
the blood PO 2 of the blood in the muscles drops, and more O 2
is removed from hemoglobin. Because the capillary bed of
contracting muscle is dilated and many previously closed cap-
illaries are open, the mean distance from the blood to the tis-
sue cells is greatly decreased; this facilitates the movement of
O 2 from blood to cells. The oxygen–hemoglobin dissociation
curve is steep in the PO 2 range below 60 mm Hg, and a rela-
tively large amount of O 2 is supplied for each drop of 1 mm
Hg in PO 2 (see Figure 36–2). Additional O 2 is supplied
because, as a result of the accumulation of CO 2 and the rise in
temperature in active tissues—and perhaps because of a rise
in red blood cell 2,3-biphosphoglycerate (2,3-BPG)—the dis-
sociation curve shifts to the right. The net effect is a threefoldFIGURE 37–15 Physiologic responses to work rate during
exercise. Changes in alveolar PCO 2 , alveolar PO, ventilation (V ̇E), CO 2
production (V ̇CO 2 ), O 2 consumption (V ̇O 2 ), arterial HCO 3 – , and arterial
pH with graded increases in work by an adult male on a bicycle ergo-
meter. Resp comp, respiratory compensation. See text for details.
(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.]V•CO 2VCO 2
(L/min-
STPD)VO 2
(L/min-
STPD)- V•O 2
V•E50120025157.407.30300PACO 2
(mm Hg)
PAO 2
(mm Hg)HCO 3 −
HCO 3 −VE
(L/min-
BTPS)pH
pH1507022 min 0Isocapnic
bufferingResp
comp(^0153045607590105120135150165180)
Work rate (watts)