The composition of the blood-brain barrier consists of endothelial cells, smooth muscle, and the pial and arachnoid membranes. It plays a role in regulating the movement of ions between blood and cerebrospinal fluid (CSF). The choroid plexus also influences the ionic composition of CSF through ion transportation. While the blood-brain barrier is impermeable to H+ and HCO3- ions, it is highly permeable to CO2. Consequently, the PCO2 in CSF generally mirrors the arterial PCO2 levels, resulting in slightly more acidic pH (7.33) in CSF compared to plasma.

Carbon dioxide (CO2) is not only brought into CSF through the blood-brain barrier but is also generated by brain cells during metabolism. This leads to a few millimeters of mercury higher PCO2 in CSF than arterial blood, contributing to its slightly more acidic pH. The smooth muscle dilation is caused by the combination of arterial carbon dioxide partial pressure (PaCO2) and CO2 generated by metabolism. Protein buffering in CSF is limited.

The carotid and aortic bodies function as peripheral chemoreceptors that respond to changes in arterial partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2), and pH. They transmit afferent information to the central respiratory control center. Peripheral chemoreceptors are the only chemoreceptors affected by changes in PaO2 and are responsible for about 40% of the ventilatory response to PaCO2. These chemoreceptors are small structures with high vascularity. They consist of type I (glomus) cells that are rich in mitochondria and endoplasmic reticulum, as well as cytoplasmic granules containing neurotransmitters such as dopamine, acetylcholine, norepinephrine, and neuropeptides. Afferent nerve fibers connect with type I cells and transmit information to the brainstem through the carotid sinus nerve (carotid body) and vagus.

The Henderson-Hasselbalch equation is utilized to determine the pH of CSF based on the bicarbonate concentration ([HCO3-]). It includes the solubility coefficient (α) and the negative logarithm of the dissociation constant for carbonic acid (pK). The equation demonstrates that an increase in CSF PCO2 leads to a decrease in CSF pH at a given [HCO3-]. This decrease in pH stimulates the central chemoreceptors, resulting in increased ventilation. Consequently, the CO2 in the blood regulates ventilation by influencing the pH of CSF. The resulting hyperventilation reduces PaCO2 and CSF PCO2, thus returning the pH of CSF towards a normal value. Additionally, an increase in PaCO2 causes cerebral vasodilation, enhancing the diffusion of CO2 into CSF. Conversely, an increase in CSF [HCO3-] leads to an increase in CSF pH at a given PaCO2.
Fig. 25.5 ). The blood-brain barrier is composed of endothelial cells, smooth muscle, and the pial and arachnoid membranes, and it regulates the movement of ions between blood and CSF. In addition, the choroid plexus also determines the ionic composition of CSF by transporting ions into and out of CSF. The blood-brain barrier is relatively impermeable by H+ and HCO3 − ions, but it is very permeable by CO2. Thus the PCO2 in CSF parallels the arterial PCO2 tension. CO2 is also produced by cells of the brain as a product of metabolism. As a consequence, the PCO2 in CSF is usually a few millimeters of mercury higher than that in arterial blood, and so the pH is slightly more acidic (7.33) in CSF than in plasma (
Table 25.1 •Fig. 25.5 Carbon Dioxide and the Blood-Brain Barrier. PaCO2crossestheblood-brainbarrierandrapidlyequilibrateswithCO2incerebrospinalfluid(CSF).H+ andHCO3− ionscrossthebarrierslowly.Thepartialpressureofarterialcarbondioxide(PaCO2)combineswithCO2generatedbymetabolismtodilatethesmoothmuscle.Incomparisonwitharterialblood,thepHofCSFislowerandthePCO2ishigher,withlittleproteinbuffering.
PCO2,partialpressureofcarbondioxide.
The carotid and aortic bodies are peripheral chemoreceptors that respond to changes in PaO2 (not the O2 content), PaCO2, and pH, and they transmit afferent information to the central respiratory control center. The peripheral chemoreceptors are the only chemoreceptors that respond to changes in PaO2. The peripheral chemoreceptors are also responsible for approximately 40% of the ventilatory response to PaCO2. These chemoreceptors are small, highly vascularized structures. They consist of type I (glomus) cells that are rich in mitochondria and endoplasmic reticulum. They also have several types of cytoplasmic granules (synaptic vesicles) that contain various neurotransmitters, including dopamine, acetylcholine, norepinephrine, and neuropeptides. Afferent nerve fibers synapse with type I cells, and they transmit information to the brainstem through the carotid sinus nerve (carotid body) and vagus
TheHenderson-Hasselbalch equation relatesthepHofCSFtotheconcentrationofbicarbonate([HCO3−]): whereα isthesolubilitycoefficient(0.03mmol/L/mmHg)andpKisthenegativelogarithmofthedissociationconstantforcarbonicacid(6.1).TheHenderson-HasselbalchequationdemonstratesthatanincreaseinCSFPCO2causesthepHofCSFtodecreaseatanygiven[HCO3−].ThedecreaseinpHstimulatesthecentralchemoreceptorsandtherebyincreasesventilation.ThusCO2inbloodregulatesventilationbyitseffectonthepHofCSF.TheresultinghyperventilationreducesthePaCO2,andthereforethePCO2ofCSF,andreturnsthepHofCSFtowardanormalvalue.Furthermore,cerebralvasodilationaccompaniesanincreaseinPaCO2,andthisenhancesthediffusionofCO2intoCSF.Incontrast,anincreaseinCSF[HCO3−]causesanincreaseinthepHofCSFatanygivenPaCO2.