Maintaining a normal physiologic acid-base balance is essential for the functioning of every organ system in the body. The renal and pulmonary systems are the primary regulators of acid-base balance. There are four principal acid-base disorders: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. A systematic approach to evaluation is critical to identify potential etiologies. A history, physical examination, metabolic profile, and arterial blood gas measurement provide a full assessment of acid-base status. However, availability of arterial blood gas measurements is usually limited outside of inpatient and emergency department settings. Calculation of an anion gap is a crucial first step for evaluating laboratory test results. Changes in serum pH, Pco2, serum bicarbonate concentration, and anion gap suggest the primary disorder, and predictable compensatory changes indicate whether a secondary acid-base disturbance is present. Mixed acid-base disorders involving the renal and pulmonary systems can occur, underscoring the importance of a systematic approach to evaluation. In the outpatient setting, primary care physicians play a vital role in identifying and treating these disorders based on initial evaluation. Prompt recognition and management of acid-base disorders can help prevent morbidity and mortality.

How ventilation (V ̇ E) matches gas exchange (V ̇ C O 2) while maintaining isocapnia during exercise remains unresolved. We measured V ̇ E , V ̇ C O 2 , arterialized-venous P C O 2 (PāCO2) and hypercapnic ventilatory responsiveness (HCVR = ∆ V ̇ E /∆ P C O 2) during four steady-state exercise intensities below the respiratory compensation point (RCP) and used a mathematical model to characterize feedforward contributions to exercise hyperpnoea and test the hypothesis that CO2 chemofeedback is inhibitory. Model assumptions were that the ventilatory response to exercise-intensity changes (GSYS = ∆ V ̇ E /∆ V ̇ C O 2) equals the sum of a feedforward exercise stimulus proportional to V ̇ C O 2 (GEX) modified by the CO2 chemoreflex (HCVR). Using experimental data GSYS was quantified as ∆ V ̇ E /∆ V ̇ C O 2 between exercise steps and GEX equalled GSYS minus chemoreflex feedback (i.e. HCVRx∆PāCO2/∆ V ̇ C O 2). Twenty healthy young participants completed a maximal cycling test and three submaximal step-incremental protocols of two 8 min stages below the estimated lactate threshold (θLT; MOD1 and MOD2) and two 12 min stages between θLT and RCP (HVY1 and HVY2). During visits 2 and 3, three rebreathing tests performed at each intensity provided HCVR (average V ̇ E -end-tidal P C O 2 slope). During visit 4, heated hand vein blood provided PāCO2 at each intensity, and V ̇ C O 2 and V ̇ E were measured by metabolic cart. With higher steady-state V ̇ C O 2 , one-way repeated-measures ANOVA showed that HCVR rose from 2.4 ± 0.9 at MOD1 to 2.8 ± 0.8, 3.2 ± 0.8 and 3.6 ± 1.0 L · min[-1] · mmHg[-1] at MOD2, HVY1 and HVY2, respectively; ∆PāCO2/∆ V ̇ C O 2 decreased (P < 0.001) from 0.2 ± 4.3 at MOD1 to -1.9 ± 5.0, -5.5 ± 4.5 and -8.0 ± 4.6 mmHg · L · min[-1]; and GEX increased (P < 0.001) from 26.9 ± 15.1 at MOD1 to 34.5 ± 20.3, 53.9 ± 19.1 and 73.4 ± 27.5 L · min[-1]. Exercise hyperpnoea may reflect the balance of intensity-dependent feedforward and inhibitory CO2 chemofeedback drive. KEY POINTS: We aimed to quantify exercise intensity-dependent changes in CO2 chemoreflexes and interpret their role in exercise hyperpnoea. Ventilatory, gas exchange, arterialized-venous P C O 2 (PāCO2) and hypercapnic ventilatory responses (HCVR) were measured during successive work-to-work cycling exercise transitions from low-to-moderate to heavy-intensity work rates. The measured HCVR at each intensity and ∆ V ̇ E /∆ V ̇ C O 2 and ∆PāCO2/∆ V ̇ C O 2 from one work rate to the next were included in a mathematical model to characterize feedforward contributions to exercise hyperpnoea at four intensities. With increasing steady-state V ̇ C O 2 , ∆ V ̇ E /∆ V ̇ C O 2 and HCVR progressively increased, whereas ∆PāCO2/∆ V ̇ C O 2 progressively became more negative. Assuming ∆ V ̇ E is the sum of a feedforward gain plus linear CO2 chemofeedback gain responding to changes in V ̇ C O 2 and P aC O 2 from rest to exercise, respectively, we estimated that feedforward gain rises with increasing exercise intensities, attaining a drive that exceeds requirements for P C O 2 regulation at its resting level. Exercise hyperpnoea, therefore, requires a feedforward exercise stimulus constrained by inhibitory chemofeedback from rest to exercise to minimize hypocapnia .

A sizable fraction of dyspneic patients with only mild to moderate COPD exhibit a heightened ventilatory response to exercise relative to metabolic demands, i.e. a high ventilation (V.E)/CO2 output (V.CO2). The lack of continuous assessment of gas exchange efficiency and estimates of arterial CO2 partial pressure has hindered our understanding of the physiological underpinnings of this dynamic phenomenon. We compared key indices of gas exchange efficiency relative to the intra-breath CO2 profile as a function of expired volume using breath-by-breath volumetric capnography in 30 patients (FEV1 = 76 ± 17%) and 30 sex- and age-matched controls during incremental cycle ergometry. Wasted ventilation in the physiological dead space (VDphys) was calculated as the sum of airway and alveolar (alv) dead space divided by tidal volume (VT). Transcutaneous (tc) readings provided estimates of arterialised PCO2. Patients exhibited lower exercise tolerance, reporting higher dyspnoea throughout exercise (p < 0.05). Higher V.E/V.CO2 was associated with higher absolute (L) alveolar dead space (VDalv), but similar VT; thus, both VDphys/VT and VDalv/VT were consistently higher in patients (p < 0.05). V.E/V.CO2 was elevated (≥34) in normocapnic patients (PtcCO2≥35 mmHg) who had a high VDphys/VT (≥0.3); conversely, high V.E/V.CO2 coexisted with a lower VDphys/VT only in hypocapnic subjects (p < 0.05). Higher VDalv and lower PtcCO2 were independently associated with a high V.E/V.CO2 nadir and iso-work rate dyspnoea (p < 0.001). Based on this innovative, high-density data-acquisition approach, we conclude that both wasted ventilation and alveolar hyperventilation, in a highly variable combination, contribute to excessive ventilation in dyspneic patients with mild-to-moderate COPD.

Studies involving breath-hold dives as deep as 60 m have identified a spike in arterial Po2 ([Formula: see text]) and Pco2 ([Formula: see text]) apparently associated with lung compression by water pressure as depth increases. Competitive breath-hold dives may exceed 100 m, raising the possibility that a spike in [Formula: see text] might contribute to narcosis-like symptoms sometimes experienced. To predict the magnitude of this spike, three elite breath-hold divers were instrumented with radial artery catheters and had arterial blood specimens taken at the bottom on separate dives to 20, 40, 60, and 80 m with another specimen either after beginning apnea but before leaving the surface (one participant) or on arrival back at the surface while still apneic (two participants). Contrary to previous expectations, the greatest spike in [Formula: see text] was at 40 m (mean: 29.3 kPa, 220 mmHg) and the trajectory of rise in [Formula: see text] also plateaued at 40 m [mean: 5.61 kPa, 42.1 mmHg (from a mean baseline of 2.53 kPa after predive hyperventilation) and 5.54 kPa, 41.6 mmHg at 60 m] before rising again after 60 m (80 m mean: 6.9 kPa, 51.5 mmHg). This suggests that a spike in arterial gases associated with lung compression was detectable until the greatest proportional changes in lung volume with increasing pressure had occurred. Thereafter, [Formula: see text] decreased through metabolism, and [Formula: see text] increased through simple metabolic accumulation. The compression effect seemed maximal at 40 m (five atmospheres absolute pressure) which may relate to the simple Boyle's law prediction that the lung may be compressed to close to residual volume (20%-30% of total lung capacity) at this pressure.NEW & NOTEWORTHY In descending deep breath-hold divers, spikes in [Formula: see text] and [Formula: see text] associated with compression of the lungs by increasing water pressure have been reported. This study, which reports the deepest arterial blood gas specimens taken to date, raises the possibility that these spikes are detectable until the greatest proportional changes in lung volume with increasing pressure have occurred, after which [Formula: see text] will decrease through metabolism and [Formula: see text] will increase through simple metabolic accumulation.