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Effects of Gas Exchange on Acid‐Base Balance

Michael I. Lindinger, George J.F. Heigenhauser

10.1002/cphy.c100055

Source: Volume 2, Issue 3, July 2012

Published online: July 2012

Full Article on Wiley Online Library



Abstract

This paper describes the interactions between ventilation and acid‐base balance under a variety of conditions including rest, exercise, altitude, pregnancy, and various muscle, respiratory, cardiac, and renal pathologies. We introduce the physicochemical approach to assessing acid‐base status and demonstrate how this approach can be used to quantify the origins of acid‐base disorders using examples from the literature. The relationships between chemoreceptor and metaboreceptor control of ventilation and acid‐base balance summarized here for adults, youth, and in various pathological conditions. There is a dynamic interplay between disturbances in acid‐base balance, that is, exercise, that affect ventilation as well as imposed or pathological disturbances of ventilation that affect acid‐base balance. Interactions between ventilation and acid‐base balance are highlighted for moderate‐ to high‐intensity exercise, altitude, induced acidosis and alkalosis, pregnancy, obesity, and some pathological conditions. In many situations, complete acid‐base data are lacking, indicating a need for further research aimed at elucidating mechanistic bases for relationships between alterations in acid‐base state and the ventilatory responses. © 2012 American Physiological Society. Compr Physiol 2:2203‐2254, 2012.

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Figure 1. Figure 1.

Diagram showing interrelationships between ventilation, acid‐base variables, and cellular processes. The dashed arrows indicate pathways through peripheral and central chemoreceptors that drive ventilation according to the acid‐base status of the individual.
Figure 2. Figure 2.

Common strong ion salts and their dissociations in body fluids. By definition, strong ions are nearly completely (> 99%) dissociated in physiological solutions. This scheme recognizes that PCr2− can be hydrolyzed to inorganic phosphate (which contributes to [Atot]) and creatine, which is uncharged.
Figure 3. Figure 3.

Relationships between the independent acid‐base variable strong ion difference ([SID]) and the dependent acid‐base variables pH, [H+] and [HCO3−] in human plasma. Plasma [Atot] was held constant at 16 mEq/L and PCO2 held constant at 40 mmHg. Note the decreasing slope in the [SID] : [H+] relationship with increasing [SID], indicating increased ability to remove H+ from solution. For comparison, the dashed – dotted line extrapolates a linear decrease in [H+] with increasing [SID]. Increasing [SID] from 39 to 45 mEq/L has the effect of buffering’ [H+] by approximately 3 nEq/L.
Figure 4. Figure 4.

The phosphate buffer system. In physiological fluids at 37°C, the phosphate species on the left side of the diagram predominate. The simultaneous dissociations of these reactions results in an apparent pK′ of 6.8 for the phosphate system. Note that hydronium (H3O+) dissociates to water and a proton.
Figure 5. Figure 5.

(A) (Top) The minute ventilation (VE)—arterial PCO2 relationship for normal humans when arterial Po2 is 100 mmHg. (Bottom) The muscle to alveolar CO2 gradient (mmHg) at rest, with high‐intensity exercise, and in a closed system at rest. (B) The effect of arterial PCO2 on VE at various levels of VCO2 as would be seen in normal individuals during exercise. Adapted, with permission, from Wasserman (329).
Figure 6. Figure 6.

A “Gamblegram” showing the concentrations of the main cations and anions in normal human plasma. [SID] is equal to the sum of [HCO3−], [A−], [Pi−], and [unmeasured anions], and [HCO3−] is equal to difference between [SID] and [A−]. A difference between the sum of cations and sum of anions would represent unmeasured anions.
Figure 7. Figure 7.

Plasma [H+] as a function of plasma PCO2, [SID], and [Atot]. Plasma [H+] isopleths (dotted lines) are shown for a range of [SID]. In panel A, [Atot] is held constant at 17 mEq/L. In panel B, PCO2 is held constant at 40 mmHg. The time course of femoral venous plasma [H+] is shown by the solid arrows; R = rest, preexercise; 0.5 = 30 s of recovery from 30 s of very high intensity leg bicycling exercise; 3.5 = 3.5 min of recovery; 9.5 = 9.5 min of recovery. Data adapted, with permission, from Kowalchuk et al. (154).
Figure 8. Figure 8.

Skeletal muscle intracellular [H+] as functions of intracellular PCO2, [Atot], and [SID]. The [H+] isopleths for [SID] = 100 mEq/L are for resting muscle, using a KA of 1.645 × 10−7 Eq/L, while the isopleths for [SID] = 60 mEq/L are for intensely exercised muscle. The dashed line isopleths in each panel are for resting muscle using the exercise muscle KA of 1.98 × 10−7 Eq/L), indicating that the increase in KA contributes to the increase in [H+] with intense exercise. Resting values for PCO2, [Atot], and [SID] are 50 mmHg, 140 mmol/L, and 100 mEq/L, respectively. These became 110 mmHg, 170 mmol/L, and 60 mEq/L, respectively, at the end of high‐intensity exercise. The time course of intracellular [H+] is shown by the solid arrows; R = rest, preexercise; 0.5 = 30 s of recovery from 30 s of very high intensity leg bicycling exercise; 3.5 = 3.5 min of recovery; 9.5 = 9.5 min of recovery. Data adapted, with permission, from Kowalchuk et al. (155).
Figure 9. Figure 9.

Respiratory chemoreflex control of ventilation. Pulmonary ventilation controls PCO2 and Po2, the forward part of the loop. Modified Stewart model equations are used to determine arterial and central H+ concentration ([H+]) by their respective PCO2, strong ion difference (SID), albumin concentration ([Alb]), and phosphate concentration ([PO43−]). [H+] and Po2 control ventilation via the respiratory chemoreflexes in the feedback part of the loop. Ventilation is also affected by drives to breathe independent of chemoreflexes, here called the wakefulness drive. Data adapted, with permission, from Ainslee and Duffin (2).
Figure 10. Figure 10.

Central (A) and peripheral (B) chemoreceptor responses to PCO2 and Po2 in terms of the drives to ventilation that they produce. Each chemoreceptor has a threshold PCO2 below which no drive is produced and above which the drive to ventilation is linearly related to PCO2 with a slope defined as the sensitivity. Models of the drive to breathe from peripheral chemoreceptors assume that the drive from peripheral chemoreceptors increases linearly with [H+] above a chemoreceptor threshold [H+] with a constant slope [sensitivity (DpS)]; therefore, sensitivity and threshold (Tp) determine the response to any particular stimulus. Inset: for the peripheral chemoreceptor sensitivity depends on Po2 in a rectangular hyperbolic relation, with asymptotes for Po2 (usually 30 mmHg) and DpS (usually 0). Data adapted, with permission, from Duffin (66).
Figure 11. Figure 11.

Complete chemoreflex model. Ventilation, dependent on PCO2 and Po2, is shown as a series of isoxic lines. Central and peripheral ventilatory neural drives (dashed and dotted lines, respectively) are added to provide total chemoreflex neural drive to breathe (solid lines) but only increase ventilation once a neural drive threshold (TD) is exceeded (heavy dashed line), establishing ventilatory recruitment PCO2 thresholds at each isoxic Po2. Central chemoreceptor threshold PCO2, when plotted against PaCO2, is less than that for the peripheral chemoreceptors because of PaCO2‐central chemoreceptor PCO2 difference (a‐c diff). (Adapted, with permission, from Ainslee and Duffin, 2).
Figure 12. Figure 12.

(A) VE (diamonds, dashed line) and o2 (triangles, dotted line) and (B) arterial PCO2 (squares, dashed line) and pH (circles, solid line), at rest and during graded exercise as a function of cardiac output in normal subjects. The data points, from left to right, represent rest, then exercise conducted at 75 W, 150 W, the ventilatory threshold, the ventilatory threshold plus 25 W, and at 90% of previously determined o2max. Data adapted, with permission, from Stickland et al. (291). (C) Breath‐by‐breath plot of end‐tidal CO2 (ET‐CO2) and of plasma [lactate−] (dashed line) of one subject performing incremental exercise to fatigue. Work rate was increased by 30 W at 1‐min intervals. Data adapted, with permission, from Hirakoba et al. (114).
Figure 13. Figure 13.

Schematic of acid‐base ventilation interactions during high‐intensity exercise.
Figure 14. Figure 14.

Plasma arterial‐venous (a‐v) differences for PCO2 (top) and [H+] bottom at rest (R), at the end of four 30 s bouts of very high intensity leg bicycling exercise with 4 min of rest between bouts, and during 90 min of recovery. Dashed lines with squares denote the a‐v difference across the arm, indicative of noncontracting tissues. The solid lines with dots denote the a‐v difference across the leg, indicative of contracting muscle. Data adapted, with permission, from McKelvie et al. (194) and Lindinger et al. (172).
Figure 15. Figure 15.

Minute ventilation (VE; inset), VCO2 (solid symbols) and o2 (open symbols) were elevated (P < 0 05) after 7 weeks of sprint training. Measurements were obtained at rest (R), during (denoted by hatched bar) and following maximal exercise (hatched bar), conducted before (triangles) and after (circles) 7 weeks of sprint training. Data adapted, with permission, from McKenna et al. (196).
Figure 16. Figure 16.

Schematic of acid‐base ventilation interactions during recovery from high‐intensity exercise. The processes shown are of significant magnitude and rate during the first 10 to 15 min of recovery, then they continue to slow and cease as the new equilibrium is established. During recovery, most of the lactate‐entering recovering muscles is in oxidative slow and fast fiber types.
Figure 17. Figure 17.

Minute ventilation (VE), respiratory exchange ratio, o2, and VCO2 after 30 s of very high intensity leg bicycling exercise. Data adapted, with permission, from Kowalchuk et al. (155).
Figure 18. Figure 18.

Arterial (solid symbols), FV (open symbols) plasma [H+] (circles), and PCO2 (triangles) at rest and after 30 s of very high intensity leg bicycling exercise. Data adapted, with permission, from Kowalchuk et al. (154).
Figure 19. Figure 19.

Arterial plasma [H+] and origins of change in[H+] in after ingestion of 0.3 g/kg body mass NaHCO3 (A) and KHCO3 (B). •, Measured arterial plasma [H+]; ○, calculated [H+] when only PCO2 changes and [SID] and [Atot]) are kept constant; ▴, calculated [H+] when only [Atot] changes and [SID] and PCO2 are kept constant; and □, calculated [H+] when only [SID] changes and PCO2 and [Atot] are kept constant. Hatched bar indicates 60‐min ingestion period. *Mean significantly different (P ≤ 0.05) from time 0. Data adapted, with permission, from Lindinger et al. (170).
Figure 20. Figure 20.

(A) Arterial plasma [SID] after ingestion of 0.3 g/kg body mass NaHCO3 (▪) and KHCO3 (•) trials. (B) Arterial plasma [Atot] in NaHCO3 and KHCO3 trials. (C) Arterial PCO2 in NaHCO3 and KHCO3 trials. Hatched bar indicates 60‐min ingestion period. *Mean significantly different (P ≤ 0.05) from time 0. Data adapted, with permission, from Lindinger et al. (170).
Figure 21. Figure 21.

Scheme of interactive processes operating during an induced respiratory alkalosis.
Figure 22. Figure 22.

Plasma pH (A), [HCO3−] (B), and [lactate] (C) before and after a maximal exercise test while breathing air (MAX, •), during exercise (to maximal under these conditions) with hypoxia (12% O2 inspired) 60 min before to 30 min after exercise (HP, ○); and submaximal (to PP maximal) exercise while breathing air (SUB, ▪). Values are means ± SD. *Significant difference between HP and MAX (P < 0.05). §Significant difference between HY and SUB. Data adapted, with permission, from Kato et al. (148).
Figure 23. Figure 23.

The relationship between plasma [lactate] and pH was significantly different with hypoxia (upper line and points) than with normoxia. Statistical analysis: regressions are parallel, but Y‐intercepts differ significantly (P < 0.01). Data adapted, with permission, from Kato et al. (148).
Figure 24. Figure 24.

Sequence of processes leading to hypoxemia, hypocapnia, and alkalosis upon exposure to altitude.
Figure 25. Figure 25.

Increasing arterial pH (ΔpHa) always leads to a rise of arterial O2 saturation (ΔSaO2), but ΔSaO2/ΔpHa increases with altitude. The O2 equilibrium curves were generated from the measured values found in Caucasians (shown in table inset). The dashed curve represents the gain in SaO2 as from the actual pHa values at the various altitudes. Data adapted, with permission, from Samaja et al. (262).
Figure 26. Figure 26.

Short‐term ventilatory acclimatization to and deacclimatization from hypoxia. As an index of alveolar ventilation, PaCO2 illustrates the temporal pattern of acute (0‐1 h) and chronic (> 1 h) ventilatory changes during exposure to 4300‐m altitude. Symbol × shows arterial PCO2 during acute normoxia after 3 days of hypoxia. Solid line with arrow depicts time during chronic hypoxia that acute normoxia was initiated. Broken line depicts time course of deacclimatization from hypoxia. Numbers in parentheses are values for Pao2 during various conditions. All symbols represent mean data for a minimum n = 6. Data adapted, with permission, from Dempsey and Forster (56).
Figure 27. Figure 27.

o2, ventilation, and arterial PCO2 during exercise at 5260 m. (A) o2 increases similarly in both groups to indistinguishable maximal values. (B) Compared with natives, lowlanders continue to hyperventilate throughout exercise. (C) Arterial PCO2 is approximately 8 mmHg lower in lowlanders at rest and throughout the range of exercise. Values are means ± SE. Data adapted, with permission, from Wagner et al. (323).
Figure 28. Figure 28.

The influence of acute altitude exposure and acid‐base manipulation on VE, VCO2, and o2 during incremental exercise. Values from the ground level test at 60 and 120 watts are shown for comparison (□). Altitude control •; altitude metabolic alkalosis (▴); altitude metabolic acidosis (○). VE was significantly increased during the altitude control compared to ground level, and during metabolic acidosis compared to metabolic alkalosis at power outputs of 60 and 80 watts. For power outputs more than 60 watts VCO2 with metabolic acidosis was significantly lower than with metabolic alkalosis. Data adapted, with permission, from McLellan et al. (198).
Figure 29. Figure 29.

Time course of plasma PCO2 (top) and pH (bottom) during incremental leg cycle exercise at ground level (•) and at altitude under normal conditions (○) and after administration of either NaHCO3− (▪) or acetazolamide (▴). Data adapted, with permission, from McLellan et al. (198).
Figure 30. Figure 30.

Mean (n = 5) minute ventilation (VE; top panel, dashed lines), arterialized hand vein plasma [lactate−] (top panel, solid lines), [H+] (lower panel, solid lines), and PCO2 (lower panel, dashed lines) at rest (some data are missing, and at 33% and 66% of control o2max. ▴ control trial; • metabolic acidosis trial; ▪ metabolic alkalosis trial. Data adapted, with permission, from Jones et al. (144).
Figure 31. Figure 31.

Plasma PCO2 before and after exercise during a maximal exercise test while breathing air (MAX, •), during exercise (to maximal under these conditions) with hypercapnia (HC; 6% CO2 inspired) 60 min before to 30 min after exercise (○); and submaximal (to hypercapnia maximal; SUB) exercise while breathing air (▪). Values are means ± SD. *Significant difference between HC and MAX (P < 0.05). †Significant difference between HC and SUB (P < 0.05). Data adapted, with permission, from Kato et al. (149).
Figure 32. Figure 32.

Plasma [lactate−] before and after exercise during a maximal exercise test while breathing air (MAX, •), during exercise (to maximal under these conditions) with hypercapnia (HC; 6% CO2 inspired) 60 min before to 30 min after exercise (○); and submaximal (to hypercapnia maximal) exercise while breathing air (▪). Values are means ± SD. *Significant difference between HC and MAX (P < 0.05). Data adapted, with permission, from Kato et al. (149).
Figure 33. Figure 33.

Plasma pH is plotted against plasma [lactate−] after exercise in normocapnic conditions (•and solid line) and in hypercapnic conditions (○ and dashed line). Linear regression equations are presented. Regression lines are parallel, but Y‐intercepts differ significantly (P < 0.001). Data adapted, with permission, from Kato et al. (149).
Figure 34. Figure 34.

Effects of pregnancy on ventilatory equivalent for CO2 (VE/VCO2), end tidal PCO2 (PETCO2), and ventilation at rest and during incremental cycle exercise. • postpartum; ○ third trimester. Data points are mean ± SE. *P < 0.05. Data adapted, with permission, from Jensen et al. (130).
Figure 35. Figure 35.

(A) Effects of human pregnancy on the central ventilatory chemoreflex response to progressive iso‐oxic hyperoxic hypercapnia in a representative subject. Note the pregnancy‐induced decrease in the central chemoreflex ventilatory recruitment threshold for PCO2 (VRTCO2) as well as the increased ventilatory response above and below this threshold, representing central chemoreflex sensitivity and wakefulness (or nonchemoreflex) drives to breathe, respectively. TM3, third trimester; PP, postpartum; PETCO2, end‐tidal PCO2. Data adapted, with permission, from Jensen et al. (132). (B) Central ventilatory chemoreflex response to hyperoxic hypercapnia in a representative pre‐ and postmenopausal subject. PET CO2, end‐tidal PCO2. Adapted, with permission, from Preston et al. (243).
Figure 36. Figure 36.

Schematic illustration of calculation of cycle CO2 balance. Dashed line, average metabolic CO2 production over time; solid line, varying breath‐by‐breath CO2 excretion measured during changes in ventilation. Difference between CO2 accumulation during event and CO2 elimination during subsequent interevent period determines CO2 balance for event‐interevent cycle. Adapted, with permission, from Berger et al. (20).
Figure 37. Figure 37.

PaCO2 (left) and [HCO3−] (right) trends over the 20‐day simulations. With isolated reduction in either renal HCO3− excretion or reduced ventilatory response, increases in PaCO2 and [HCO3−] occurred. In contrast, the relatively small effects of blunted respiratory control alone and reduced renal HCO3− excretion alone show marked synergism when both occur simultaneously. Adapted, with permission, from Norman et al. (219).
Figure 38. Figure 38.

The model's time course (light line, open circles) of HCO3 kinetics compared with experimentally obtained values (heavy line; in dogs, taken from Polak et al. 1961). The x‐axis plots days from either the onset (left panel) or removal (right panel) of hypercapnia. The y‐axis shows the change in [HCO3−] at the end of each day expressed as a percentage of the final change. Adapted, with permission, from Norman et al. (219).
Figure 39. Figure 39.

(A) Minute ventilation (VE) as a function of arterial plasma pH in individuals with diabetic ketoacidosis. Points represent data from Kety and Polis (152). (B) Arterial plasma pH as a function of PCO2, showing isopleths for plasma [HCO3−] and cerebrospinal fluid pH (pHCSF). Open square are data,taken with permission, from Kety and Polis (152) in conscious patients with diabetic ketoacidosis (DKA). Solid circle denote the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics data in children with DKA who go on to develop cerebral edema. Solid triangle are data taken, with permission, from Glaser et al. (91) from children who had DKA and cerebral edema.
Figure 40. Figure 40.

Minute ventilation (VE) as a function of end‐tidal PCO2 in control subjects (n = 10) and patients (n = 6) with chronic renal failure receiving chronic hemodialysis. Adapted, with permission, from Burgess et al. (30).


Figure 1.

Diagram showing interrelationships between ventilation, acid‐base variables, and cellular processes. The dashed arrows indicate pathways through peripheral and central chemoreceptors that drive ventilation according to the acid‐base status of the individual.



Figure 2.

Common strong ion salts and their dissociations in body fluids. By definition, strong ions are nearly completely (> 99%) dissociated in physiological solutions. This scheme recognizes that PCr2− can be hydrolyzed to inorganic phosphate (which contributes to [Atot]) and creatine, which is uncharged.



Figure 3.

Relationships between the independent acid‐base variable strong ion difference ([SID]) and the dependent acid‐base variables pH, [H+] and [HCO3−] in human plasma. Plasma [Atot] was held constant at 16 mEq/L and PCO2 held constant at 40 mmHg. Note the decreasing slope in the [SID] : [H+] relationship with increasing [SID], indicating increased ability to remove H+ from solution. For comparison, the dashed – dotted line extrapolates a linear decrease in [H+] with increasing [SID]. Increasing [SID] from 39 to 45 mEq/L has the effect of buffering’ [H+] by approximately 3 nEq/L.



Figure 4.

The phosphate buffer system. In physiological fluids at 37°C, the phosphate species on the left side of the diagram predominate. The simultaneous dissociations of these reactions results in an apparent pK′ of 6.8 for the phosphate system. Note that hydronium (H3O+) dissociates to water and a proton.



Figure 5.

(A) (Top) The minute ventilation (VE)—arterial PCO2 relationship for normal humans when arterial Po2 is 100 mmHg. (Bottom) The muscle to alveolar CO2 gradient (mmHg) at rest, with high‐intensity exercise, and in a closed system at rest. (B) The effect of arterial PCO2 on VE at various levels of VCO2 as would be seen in normal individuals during exercise. Adapted, with permission, from Wasserman (329).



Figure 6.

A “Gamblegram” showing the concentrations of the main cations and anions in normal human plasma. [SID] is equal to the sum of [HCO3−], [A−], [Pi−], and [unmeasured anions], and [HCO3−] is equal to difference between [SID] and [A−]. A difference between the sum of cations and sum of anions would represent unmeasured anions.



Figure 7.

Plasma [H+] as a function of plasma PCO2, [SID], and [Atot]. Plasma [H+] isopleths (dotted lines) are shown for a range of [SID]. In panel A, [Atot] is held constant at 17 mEq/L. In panel B, PCO2 is held constant at 40 mmHg. The time course of femoral venous plasma [H+] is shown by the solid arrows; R = rest, preexercise; 0.5 = 30 s of recovery from 30 s of very high intensity leg bicycling exercise; 3.5 = 3.5 min of recovery; 9.5 = 9.5 min of recovery. Data adapted, with permission, from Kowalchuk et al. (154).



Figure 8.

Skeletal muscle intracellular [H+] as functions of intracellular PCO2, [Atot], and [SID]. The [H+] isopleths for [SID] = 100 mEq/L are for resting muscle, using a KA of 1.645 × 10−7 Eq/L, while the isopleths for [SID] = 60 mEq/L are for intensely exercised muscle. The dashed line isopleths in each panel are for resting muscle using the exercise muscle KA of 1.98 × 10−7 Eq/L), indicating that the increase in KA contributes to the increase in [H+] with intense exercise. Resting values for PCO2, [Atot], and [SID] are 50 mmHg, 140 mmol/L, and 100 mEq/L, respectively. These became 110 mmHg, 170 mmol/L, and 60 mEq/L, respectively, at the end of high‐intensity exercise. The time course of intracellular [H+] is shown by the solid arrows; R = rest, preexercise; 0.5 = 30 s of recovery from 30 s of very high intensity leg bicycling exercise; 3.5 = 3.5 min of recovery; 9.5 = 9.5 min of recovery. Data adapted, with permission, from Kowalchuk et al. (155).



Figure 9.

Respiratory chemoreflex control of ventilation. Pulmonary ventilation controls PCO2 and Po2, the forward part of the loop. Modified Stewart model equations are used to determine arterial and central H+ concentration ([H+]) by their respective PCO2, strong ion difference (SID), albumin concentration ([Alb]), and phosphate concentration ([PO43−]). [H+] and Po2 control ventilation via the respiratory chemoreflexes in the feedback part of the loop. Ventilation is also affected by drives to breathe independent of chemoreflexes, here called the wakefulness drive. Data adapted, with permission, from Ainslee and Duffin (2).



Figure 10.

Central (A) and peripheral (B) chemoreceptor responses to PCO2 and Po2 in terms of the drives to ventilation that they produce. Each chemoreceptor has a threshold PCO2 below which no drive is produced and above which the drive to ventilation is linearly related to PCO2 with a slope defined as the sensitivity. Models of the drive to breathe from peripheral chemoreceptors assume that the drive from peripheral chemoreceptors increases linearly with [H+] above a chemoreceptor threshold [H+] with a constant slope [sensitivity (DpS)]; therefore, sensitivity and threshold (Tp) determine the response to any particular stimulus. Inset: for the peripheral chemoreceptor sensitivity depends on Po2 in a rectangular hyperbolic relation, with asymptotes for Po2 (usually 30 mmHg) and DpS (usually 0). Data adapted, with permission, from Duffin (66).



Figure 11.

Complete chemoreflex model. Ventilation, dependent on PCO2 and Po2, is shown as a series of isoxic lines. Central and peripheral ventilatory neural drives (dashed and dotted lines, respectively) are added to provide total chemoreflex neural drive to breathe (solid lines) but only increase ventilation once a neural drive threshold (TD) is exceeded (heavy dashed line), establishing ventilatory recruitment PCO2 thresholds at each isoxic Po2. Central chemoreceptor threshold PCO2, when plotted against PaCO2, is less than that for the peripheral chemoreceptors because of PaCO2‐central chemoreceptor PCO2 difference (a‐c diff). (Adapted, with permission, from Ainslee and Duffin, 2).



Figure 12.

(A) VE (diamonds, dashed line) and o2 (triangles, dotted line) and (B) arterial PCO2 (squares, dashed line) and pH (circles, solid line), at rest and during graded exercise as a function of cardiac output in normal subjects. The data points, from left to right, represent rest, then exercise conducted at 75 W, 150 W, the ventilatory threshold, the ventilatory threshold plus 25 W, and at 90% of previously determined o2max. Data adapted, with permission, from Stickland et al. (291). (C) Breath‐by‐breath plot of end‐tidal CO2 (ET‐CO2) and of plasma [lactate−] (dashed line) of one subject performing incremental exercise to fatigue. Work rate was increased by 30 W at 1‐min intervals. Data adapted, with permission, from Hirakoba et al. (114).



Figure 13.

Schematic of acid‐base ventilation interactions during high‐intensity exercise.



Figure 14.

Plasma arterial‐venous (a‐v) differences for PCO2 (top) and [H+] bottom at rest (R), at the end of four 30 s bouts of very high intensity leg bicycling exercise with 4 min of rest between bouts, and during 90 min of recovery. Dashed lines with squares denote the a‐v difference across the arm, indicative of noncontracting tissues. The solid lines with dots denote the a‐v difference across the leg, indicative of contracting muscle. Data adapted, with permission, from McKelvie et al. (194) and Lindinger et al. (172).



Figure 15.

Minute ventilation (VE; inset), VCO2 (solid symbols) and o2 (open symbols) were elevated (P < 0 05) after 7 weeks of sprint training. Measurements were obtained at rest (R), during (denoted by hatched bar) and following maximal exercise (hatched bar), conducted before (triangles) and after (circles) 7 weeks of sprint training. Data adapted, with permission, from McKenna et al. (196).



Figure 16.

Schematic of acid‐base ventilation interactions during recovery from high‐intensity exercise. The processes shown are of significant magnitude and rate during the first 10 to 15 min of recovery, then they continue to slow and cease as the new equilibrium is established. During recovery, most of the lactate‐entering recovering muscles is in oxidative slow and fast fiber types.



Figure 17.

Minute ventilation (VE), respiratory exchange ratio, o2, and VCO2 after 30 s of very high intensity leg bicycling exercise. Data adapted, with permission, from Kowalchuk et al. (155).



Figure 18.

Arterial (solid symbols), FV (open symbols) plasma [H+] (circles), and PCO2 (triangles) at rest and after 30 s of very high intensity leg bicycling exercise. Data adapted, with permission, from Kowalchuk et al. (154).



Figure 19.

Arterial plasma [H+] and origins of change in[H+] in after ingestion of 0.3 g/kg body mass NaHCO3 (A) and KHCO3 (B). •, Measured arterial plasma [H+]; ○, calculated [H+] when only PCO2 changes and [SID] and [Atot]) are kept constant; ▴, calculated [H+] when only [Atot] changes and [SID] and PCO2 are kept constant; and □, calculated [H+] when only [SID] changes and PCO2 and [Atot] are kept constant. Hatched bar indicates 60‐min ingestion period. *Mean significantly different (P ≤ 0.05) from time 0. Data adapted, with permission, from Lindinger et al. (170).



Figure 20.

(A) Arterial plasma [SID] after ingestion of 0.3 g/kg body mass NaHCO3 (▪) and KHCO3 (•) trials. (B) Arterial plasma [Atot] in NaHCO3 and KHCO3 trials. (C) Arterial PCO2 in NaHCO3 and KHCO3 trials. Hatched bar indicates 60‐min ingestion period. *Mean significantly different (P ≤ 0.05) from time 0. Data adapted, with permission, from Lindinger et al. (170).



Figure 21.

Scheme of interactive processes operating during an induced respiratory alkalosis.



Figure 22.

Plasma pH (A), [HCO3−] (B), and [lactate] (C) before and after a maximal exercise test while breathing air (MAX, •), during exercise (to maximal under these conditions) with hypoxia (12% O2 inspired) 60 min before to 30 min after exercise (HP, ○); and submaximal (to PP maximal) exercise while breathing air (SUB, ▪). Values are means ± SD. *Significant difference between HP and MAX (P < 0.05). §Significant difference between HY and SUB. Data adapted, with permission, from Kato et al. (148).



Figure 23.

The relationship between plasma [lactate] and pH was significantly different with hypoxia (upper line and points) than with normoxia. Statistical analysis: regressions are parallel, but Y‐intercepts differ significantly (P < 0.01). Data adapted, with permission, from Kato et al. (148).



Figure 24.

Sequence of processes leading to hypoxemia, hypocapnia, and alkalosis upon exposure to altitude.



Figure 25.

Increasing arterial pH (ΔpHa) always leads to a rise of arterial O2 saturation (ΔSaO2), but ΔSaO2/ΔpHa increases with altitude. The O2 equilibrium curves were generated from the measured values found in Caucasians (shown in table inset). The dashed curve represents the gain in SaO2 as from the actual pHa values at the various altitudes. Data adapted, with permission, from Samaja et al. (262).



Figure 26.

Short‐term ventilatory acclimatization to and deacclimatization from hypoxia. As an index of alveolar ventilation, PaCO2 illustrates the temporal pattern of acute (0‐1 h) and chronic (> 1 h) ventilatory changes during exposure to 4300‐m altitude. Symbol × shows arterial PCO2 during acute normoxia after 3 days of hypoxia. Solid line with arrow depicts time during chronic hypoxia that acute normoxia was initiated. Broken line depicts time course of deacclimatization from hypoxia. Numbers in parentheses are values for Pao2 during various conditions. All symbols represent mean data for a minimum n = 6. Data adapted, with permission, from Dempsey and Forster (56).



Figure 27.

o2, ventilation, and arterial PCO2 during exercise at 5260 m. (A) o2 increases similarly in both groups to indistinguishable maximal values. (B) Compared with natives, lowlanders continue to hyperventilate throughout exercise. (C) Arterial PCO2 is approximately 8 mmHg lower in lowlanders at rest and throughout the range of exercise. Values are means ± SE. Data adapted, with permission, from Wagner et al. (323).



Figure 28.

The influence of acute altitude exposure and acid‐base manipulation on VE, VCO2, and o2 during incremental exercise. Values from the ground level test at 60 and 120 watts are shown for comparison (□). Altitude control •; altitude metabolic alkalosis (▴); altitude metabolic acidosis (○). VE was significantly increased during the altitude control compared to ground level, and during metabolic acidosis compared to metabolic alkalosis at power outputs of 60 and 80 watts. For power outputs more than 60 watts VCO2 with metabolic acidosis was significantly lower than with metabolic alkalosis. Data adapted, with permission, from McLellan et al. (198).



Figure 29.

Time course of plasma PCO2 (top) and pH (bottom) during incremental leg cycle exercise at ground level (•) and at altitude under normal conditions (○) and after administration of either NaHCO3− (▪) or acetazolamide (▴). Data adapted, with permission, from McLellan et al. (198).



Figure 30.

Mean (n = 5) minute ventilation (VE; top panel, dashed lines), arterialized hand vein plasma [lactate−] (top panel, solid lines), [H+] (lower panel, solid lines), and PCO2 (lower panel, dashed lines) at rest (some data are missing, and at 33% and 66% of control o2max. ▴ control trial; • metabolic acidosis trial; ▪ metabolic alkalosis trial. Data adapted, with permission, from Jones et al. (144).



Figure 31.

Plasma PCO2 before and after exercise during a maximal exercise test while breathing air (MAX, •), during exercise (to maximal under these conditions) with hypercapnia (HC; 6% CO2 inspired) 60 min before to 30 min after exercise (○); and submaximal (to hypercapnia maximal; SUB) exercise while breathing air (▪). Values are means ± SD. *Significant difference between HC and MAX (P < 0.05). †Significant difference between HC and SUB (P < 0.05). Data adapted, with permission, from Kato et al. (149).



Figure 32.

Plasma [lactate−] before and after exercise during a maximal exercise test while breathing air (MAX, •), during exercise (to maximal under these conditions) with hypercapnia (HC; 6% CO2 inspired) 60 min before to 30 min after exercise (○); and submaximal (to hypercapnia maximal) exercise while breathing air (▪). Values are means ± SD. *Significant difference between HC and MAX (P < 0.05). Data adapted, with permission, from Kato et al. (149).



Figure 33.

Plasma pH is plotted against plasma [lactate−] after exercise in normocapnic conditions (•and solid line) and in hypercapnic conditions (○ and dashed line). Linear regression equations are presented. Regression lines are parallel, but Y‐intercepts differ significantly (P < 0.001). Data adapted, with permission, from Kato et al. (149).



Figure 34.

Effects of pregnancy on ventilatory equivalent for CO2 (VE/VCO2), end tidal PCO2 (PETCO2), and ventilation at rest and during incremental cycle exercise. • postpartum; ○ third trimester. Data points are mean ± SE. *P < 0.05. Data adapted, with permission, from Jensen et al. (130).



Figure 35.

(A) Effects of human pregnancy on the central ventilatory chemoreflex response to progressive iso‐oxic hyperoxic hypercapnia in a representative subject. Note the pregnancy‐induced decrease in the central chemoreflex ventilatory recruitment threshold for PCO2 (VRTCO2) as well as the increased ventilatory response above and below this threshold, representing central chemoreflex sensitivity and wakefulness (or nonchemoreflex) drives to breathe, respectively. TM3, third trimester; PP, postpartum; PETCO2, end‐tidal PCO2. Data adapted, with permission, from Jensen et al. (132). (B) Central ventilatory chemoreflex response to hyperoxic hypercapnia in a representative pre‐ and postmenopausal subject. PET CO2, end‐tidal PCO2. Adapted, with permission, from Preston et al. (243).



Figure 36.

Schematic illustration of calculation of cycle CO2 balance. Dashed line, average metabolic CO2 production over time; solid line, varying breath‐by‐breath CO2 excretion measured during changes in ventilation. Difference between CO2 accumulation during event and CO2 elimination during subsequent interevent period determines CO2 balance for event‐interevent cycle. Adapted, with permission, from Berger et al. (20).



Figure 37.

PaCO2 (left) and [HCO3−] (right) trends over the 20‐day simulations. With isolated reduction in either renal HCO3− excretion or reduced ventilatory response, increases in PaCO2 and [HCO3−] occurred. In contrast, the relatively small effects of blunted respiratory control alone and reduced renal HCO3− excretion alone show marked synergism when both occur simultaneously. Adapted, with permission, from Norman et al. (219).



Figure 38.

The model's time course (light line, open circles) of HCO3 kinetics compared with experimentally obtained values (heavy line; in dogs, taken from Polak et al. 1961). The x‐axis plots days from either the onset (left panel) or removal (right panel) of hypercapnia. The y‐axis shows the change in [HCO3−] at the end of each day expressed as a percentage of the final change. Adapted, with permission, from Norman et al. (219).



Figure 39.

(A) Minute ventilation (VE) as a function of arterial plasma pH in individuals with diabetic ketoacidosis. Points represent data from Kety and Polis (152). (B) Arterial plasma pH as a function of PCO2, showing isopleths for plasma [HCO3−] and cerebrospinal fluid pH (pHCSF). Open square are data,taken with permission, from Kety and Polis (152) in conscious patients with diabetic ketoacidosis (DKA). Solid circle denote the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics data in children with DKA who go on to develop cerebral edema. Solid triangle are data taken, with permission, from Glaser et al. (91) from children who had DKA and cerebral edema.



Figure 40.

Minute ventilation (VE) as a function of end‐tidal PCO2 in control subjects (n = 10) and patients (n = 6) with chronic renal failure receiving chronic hemodialysis. Adapted, with permission, from Burgess et al. (30).

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Article Title: Effects of Gas Exchange on Acid‐Base Balance
 

How to Cite

Michael I. Lindinger, George J.F. Heigenhauser. Effects of Gas Exchange on Acid‐Base Balance. Compr Physiol 2012, 2: 2203-2254. doi: 10.1002/cphy.c100055