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Homeostatic mechanisms are activated to return the pH back to normal when there are changes in pH that result from alterations in PaCO2. The pH of the cerebrospinal fluid (CSF) is regulated by the blood-brain barrier, which adjusts the ionic composition and [HCO3-] of the CSF. However, changes in CSF [HCO3-] occur slowly over several hours, while changes in CSF PCO2 can occur within minutes. Therefore, it takes hours for compensation for changes in CSF pH to fully develop.

Ventilation and ventilatory patterns are influenced by several reflexes originating from the chest wall and lungs (see Table 25.2). The Hering-Breuer inspiratory-inhibitory reflex is stimulated by increases in lung volume, particularly when associated with an increase in both ventilatory rate and tidal volume. This reflex, mediated by vagal fibers, responds to stretch and is activated by the stretch receptors located in the airway smooth muscles. Type I cells in the aortic and carotid bodies primarily sense PaO2, PaCO2, and pH. A decrease in PaO2 leads to an increase in chemoreceptor discharge, which in turn enhances respiration. The response is more pronounced when PaO2 falls below 75 mm Hg. Therefore, ventilation is regulated by changes in arterial and CSF pH through their effects on peripheral and central chemoreceptors (see Fig. 25.6).

During chronic metabolic acidosis, such as diabetic ketoacidosis, the [H+] in CSF increases, resulting in an increased ventilatory response to inspired PaCO2 (steeper slope). Conversely, during chronic metabolic alkalosis (a relatively uncommon condition), the [H+] in CSF decreases, leading to a decreased ventilatory response to inspired PaCO2 (reduced slope). The positions of the response lines are also shifted, indicating altered thresholds.

Imagine traveling from New York City to Denver. The barometric pressure in New York is approximately 760 mmHg, while in the surrounding mountains of Denver, Colorado, it is 600 mmHg. At sea level, the PaO2 is around 95 mmHg, and using the alveolar air equation (see ), PAO2= [(760 - 47) × 0.21] - [40/0.8] = 100 mmHg. If the alveolar-arterial PO2 difference [AaDO2] is 5 mmHg, then PaO2 = 100 mmHg - 5 mmHg = 95 mmHg. In the CSF, the pH would be approximately 7.33, the PaCO2 would be 44 mmHg (PaCO2 + CO2 produced by the metabolism of brain cells), and the HCO3- would be approximately 22 mEq/L.

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ChangesinPaCO2thatresultfromalterationsinpHactivatehomeostaticmechanismsthatreturnthepHbacktowardanormalvalue.Theblood-brainbarrierregulatesthepHofCSFbyadjustingtheioniccompositionand[HCO3 −]ofCSF.ThesechangesinCSF[HCO3−],however,occurslowly,overaperiodofseveralhours,whereaschangesinCSFPCO2canoccurwithinminutes.ThuscompensationforchangesinthepHofCSFrequireshourstodevelopfully.
Several reflexes that arise from the chest wall and lungs affect ventilation and ventilatory patterns (
Table 25.2 ). The Hering-Breuer inspiratory-inhibitory reflex is stimulated by increases in lung volume, especially those associated with an increase in both ventilatory rate and tidal volume. This stretch reflex is mediated by vagal fibers, and when nerve (aortic body). Type I cells are the cells primarily responsible for sensing PaO2, PaCO2, and pH. In response to even small decreases in PaO2, there is an increase in chemoreceptor discharge, which enhances respiration. The response is robust when PaO2 decreases below 75 mm Hg. Thus ventilation is regulated by changes in arterial and CSF pH through effects on peripheral and central chemoreceptors (
Fig. 25.6 •Fig. 25.6 The Ventilatory Response to Partial Pressure of Arterial Carbon Dioxide (PaCO2) is Affected by the Concentration of Hydrogen ([H+]) in Cerebrospinal Fluid (CSF) and Brainstem Interstitial Fluid. Duringchronicmetabolicacidosis(e.g.,diabeticketoacidosis),the[H+]inCSFisincreased,andtheventilatoryresponsetoinspiredPaCO2isincreased(steeperslope).Conversely,duringchronicmetabolicalkalosis(arelativelyuncommoncondition),the[H+]inCSFisdecreasedandtheventilatoryresponsetoinspiredPaCO2isdecreased(reducedslope).Thepositionsoftheresponselinesarealsoshifted,whichindicatesalteredthresholds.
ImagineflyingfromNewYorkCitytoDenver.ThebarometricpressureinNewYorkisapproximately760mmHg,whereasinthemountainssurroundingDenver,Colorado,itis600mmHg.Atsealevel,thePaO2isapproximately95mmHgandPAO2= [(760− 47)× 0.21]− [40/0.8]= 100mmHg(accordingtothealveolarairequation;see ).Ifthealveolar-arterialPO2difference[AaDO2]is5mmHg,PaO2= 100mmHg− 5mmHg= 95mmHg.IntheCSF,pHwouldbeapproximately7.33,PaCO2wouldbe44mmHg(PaCO2+ CO2producedbymetabolismofbraincells),andHCO3− wouldbeapproximately22mEq/L.