Upon arrival in Denver, there is a sudden decrease in the partial pressure of inspired oxygen (PiO2), resulting in PiO2 = (600 - 47) x 0.21 = 116 mmHg. Additionally, there are decreases in the partial pressures of alveolar and arterial oxygen, with PAO2 = 116 - (40/0.8) = 66 mmHg, and PaO2 = 61 mmHg if AaDO2 remains unchanged. This decline in arterial oxygen triggers the peripheral chemoreceptors, leading to an increase in ventilation. This increase in ventilation reduces PaCO2 and raises arterial pH. The purpose of this heightened ventilation is to minimize hypoxemia by elevating PAO2. For instance, if PACO2 decreases to 30 mmHg, then PAO2 = [(600 - 47) x 0.21] - [30/0.8] = 78 mmHg, reflecting a 12 mmHg increase in PAO2.

The decrease in PaCO2 also causes a decline in the PCO2 of cerebrospinal fluid (CSF). As [HCO3-] remains unchanged, the pH of CSF increases. This rise in CSF pH dampens the discharge rate of central chemoreceptors and reduces their contribution to the ventilatory drive. Over the next 12 to 36 hours, [HCO3-] in CSF decreases as acid-base transporter proteins at the blood-brain barrier reduce [HCO3-]. Consequently, the pH of CSF returns to normal. Central chemoreceptor discharge increases, leading to further augmentation of minute ventilation. Simultaneously, [HCO3-] in CSF gradually gets excreted from plasma by the kidneys, resulting in a gradual return of arterial pH toward normal values. As arterial pH becomes normal, peripheral chemoreceptor stimulation increases. Ultimately, within 36 hours of arrival at high altitude, minute ventilation significantly increases. This delayed response is more substantial than the immediate effect of hypoxemia on ventilation. The further increase in ventilation is due to stimulation of both central and peripheral chemoreceptors. Thus, after 36 hours, both arterial pH and CSF pH are approaching normal values, minute ventilation is increased, PaO2 is decreased, and PaCO2 is decreased.

Upon returning home to New York, PiO2 returns to a normal value, removing the hypoxic stimulus to ventilation. PaO2 returns to normal, and the stimulation of peripheral chemoreceptors to ventilation decreases. This causes an increase in arterial [CO2] toward normal values, which, in turn, leads to an increase in CSF [CO2]. This increase is associated with a decrease in CSF pH as [HCO3-] in CSF is reduced and ventilation is enhanced. Over the next 12 to 36 hours, the acid-base transporters in the blood-brain barrier transport HCO3- back into CSF, gradually restoring the pH of CSF toward normal values. Similarly, the pH of blood decreases as PaCO2 rises due to the decrease in arterial [HCO3-]. This stimulates the peripheral chemoreceptors, and minute ventilation remains augmented. Over the next 12 to 36 hours, blood [HCO3-] increases in the kidneys, arterial pH returns to a normal value, and minute ventilation returns to a normal level.
WhenyouarriveinDenver,thereisanabruptdecreaseinthepartialpressureofinspiredO2(PiO2):PiO2= (600− 47)× 0.21= 116mmHg;therearealsodecreasesinthepartialpressuresofalveolarandarterialO2:PAO2= 116− (40/0.8)= 66mmHg,andPaO2= 61mmHgifthereisnochangeinAaDO2).ThisdecreaseinarterialO2stimulatestheperipheralchemoreceptorsandtherebyincreasesventilation.TheincreaseinventilationdecreasesPaCO2andelevatesarterialpH.TheresultofthisincreaseinventilationistominimizethehypoxemiabyincreasingPAO2.Forexample,assumethatPACO2decreasesto30mmHg.ThenPAO2= [(600− 47)× 0.21]− [30/0.8]= 78mmHg,a12–mmHgincreaseinPAO2.
ThedecreaseinPaCO2alsocausesadecreaseinthePCO2ofCSF.Because[HCO3−]isunchanged,thepHofCSFincreases.ThisincreaseinthepHofCSFattenuatestherateofdischargeofthecentralchemoreceptorsanddecreasestheircontributiontotheventilatorydrive.Overthenext12to36hours,[HCO3−]inCSFdecreasesasacid-basetransporterproteinsintheblood-brainbarrierreduce[HCO3−].Asaconsequence,thepHofCSFreturnstowardnormal.Centralchemoreceptordischargeincreases,andminuteventilationisfurtherincreased.Atthesametimethat[HCO3−]inCSFdecreases,HCO3− isgraduallyexcretedfromplasmabythekidneys.ThisresultsinagradualreturnofarterialpHtowardnormalvalues.PeripheralchemoreceptorstimulationincreasesfurtherasarterialpHbecomesnormal(peripheralchemoreceptorsareinhibitedbytheelevatedarterialpH).Finally,within36hoursofarrivingathighaltitude,minuteventilationincreasessignificantly.Thisdelayedresponseisgreaterthantheimmediateeffectofthehypoxemiaonventilation.Thisfurtherincreaseinventilationisduetobothcentralandperipheralchemoreceptorstimulation.Thusafter36hours,botharterialpHandCSFpHareapproachingnormalvalues;minuteventilationisincreased,PaO2isdecreased,andPaCO2isdecreased.
Younowreturnhome.WhenyoulandinNewYork,thePiO2returnstoanormalvalue,andthehypoxicstimulustoventilationisremoved.PaO2returnstoanormalvalue,andtheperipheralchemoreceptorstimulationtoventilationdecreases.Thiscausesanincreaseinarterial[CO2]towardnormalvalues,whichinturncausesanincreaseinCSF[CO2].ThisincreaseisassociatedwithadecreaseinthepHofCSFas[HCO3−]inCSFisreducedandventilationisaugmented.Overthenext12to36hours,theacid-basetransportersintheblood-brainbarriertransportHCO3− backintoCSF,andthepHofCSFgraduallyreturnstowardnormalvalues.Similarly,thepHofblooddecreasesasPaCO2risesbecausearterial[HCO3−]decreases.Thisstimulatestheperipheralchemoreceptors,andminuteventilationremainsaugmented.Overthenext12to36hours,blood[HCO3−]increasesinthekidneys(see ),arterialpHreturnstoanormalvalue,andminuteventilationreturnstoanormallevel.