Acid‐Base Balance in Cerebral Fluids

Respiratory Physiology > Control of Breathing > Central Nervous Control

Email a friend
Contact the editor about this article
How to cite

Vladimir Fencl

10.1002/cphy.cp030204

Source: Supplement 11: Handbook of Physiology, The Respiratory System, Control of Breathing

Originally published: 1986

Published online: January 2011

Full Article on Wiley Online Library

Abstract
Images
References

Abstract

The sections in this article are:

1 Structural and Functional Considerations

1.1 Turnover Rate of Cerebral Fluids

1.2 Barriers Between Cerebral Fluids and Blood

1.3 Exchanges Between CSF and Cerebral ISF

1.4 Ionic Composition of Cerebral Fluids

2 Acid‐Base Balance in Cerebral Fluids

2.1 Normal Acid‐Base Balance

2.2 Acid‐Base Disturbances

2.3 Relationships Between CSF and ISF in Acid‐Base Disturbances

2.4 Conclusions

	Figure 1. Relation between pH of arterial blood plasma and of lumbar CSF in humans during stable nonrespiratory (metabolic) acidosis or alkalosis. Symbols, mean values reported by different authors. From Siesjö 152
	Figure 2. Relation between pH of arterial blood plasma and of lumbar CSF in humans during stable respiratory alkalosis (hypocapnia) or acidosis (hypercapnia). Symbols, mean values reported by different authors. From Siesjö 152
	Figure 3. Relation between pH of arterial blood plasma and of lumbar CSF in humans during stable acid‐base disturbances of metabolic (M) and respiratory (R) origin. Curves constructed from compiled data on relative changes in [H⁺] in fluids. Data from Clark et al. 31, Dempsey et al. 41, and Fencl 45
	Figure 4. Relation between [] in arterial plasma and in CSF in humans during stable acid‐base disturbances of respiratory and metabolic origin. Solid line, metabolic acidosis and alkalosis 45; dashed line, respiratory alkalosis and acidosis; x, values at = 24–60 Torr (data from refs. 31,42,53,142,143,146,150,170); ⊗, mean values in 3 groups of patients with > 70 Torr data from refs. 66,146,167
	Figure 5. Model of CSF secretion. A: relative fluxes. Lengths of arrows indicate relative sizes of ion fluxes through membranes. B: relative permeabilities. From Woodbury 181
	Figure 6. A: in cerebral tissue and CSF is determined mainly by value of during given systemic acid‐base condition and to a minor degree by changes in cerebral blood flow (CBF) produced by acid‐base disturbance. B: processes of interaction between fluid compartments. 1) Choroidal fluid formation involving active transport of strong ions (blood‐CSF barrier). 2) Cerebral ISF formation involving active transport of strong ions (blood‐brain barrier). 3) Exchanges between cerebral ISF and brain cells: a) production or consumption of metabolic acids; b) “cellular buffering” involving exchange of strong cations and anions (chloride shift). 4) Bulk flow of cerebral ISF (?). 5) Passive diffusional exchanges of strong ions between CSF and ISF. 6) “Cellular buffering” by RBCs involving exchange of strong cations and anions between plasma and intracellular fluid of RBCs (chloride shift).

Figure 1.

Relation between pH of arterial blood plasma and of lumbar CSF in humans during stable nonrespiratory (metabolic) acidosis or alkalosis. Symbols, mean values reported by different authors.

From Siesjö 152

Figure 2.

Relation between pH of arterial blood plasma and of lumbar CSF in humans during stable respiratory alkalosis (hypocapnia) or acidosis (hypercapnia). Symbols, mean values reported by different authors.

From Siesjö 152

Figure 3.

Relation between pH of arterial blood plasma and of lumbar CSF in humans during stable acid‐base disturbances of metabolic (M) and respiratory (R) origin. Curves constructed from compiled data on relative changes in [H⁺] in fluids.

Data from Clark et al. 31, Dempsey et al. 41, and Fencl 45

Figure 4.

Relation between [] in arterial plasma and in CSF in humans during stable acid‐base disturbances of respiratory and metabolic origin. Solid line, metabolic acidosis and alkalosis 45; dashed line, respiratory alkalosis and acidosis; x, values at = 24–60 Torr (data from refs. 31,42,53,142,143,146,150,170); ⊗, mean values in 3 groups of patients with > 70 Torr

data from refs. 66,146,167

Figure 5.

Model of CSF secretion. A: relative fluxes. Lengths of arrows indicate relative sizes of ion fluxes through membranes. B: relative permeabilities.

From Woodbury 181

Figure 6.

A: in cerebral tissue and CSF is determined mainly by value of during given systemic acid‐base condition and to a minor degree by changes in cerebral blood flow (CBF) produced by acid‐base disturbance. B: processes of interaction between fluid compartments. 1) Choroidal fluid formation involving active transport of strong ions (blood‐CSF barrier). 2) Cerebral ISF formation involving active transport of strong ions (blood‐brain barrier). 3) Exchanges between cerebral ISF and brain cells: a) production or consumption of metabolic acids; b) “cellular buffering” involving exchange of strong cations and anions (chloride shift). 4) Bulk flow of cerebral ISF (?). 5) Passive diffusional exchanges of strong ions between CSF and ISF. 6) “Cellular buffering” by RBCs involving exchange of strong cations and anions between plasma and intracellular fluid of RBCs (chloride shift).

References
1.	Abbot, J., H. Davson, I. Glen, and N. Grant. Chloride transport and potential across the blood‐CSF barrier. Brain Res. 29: 185–193, 1971.
2.	Adaro, F. V. M., E. E. Roehr, A. R. Viola, and C. Wymersberg de Obrutzky. Acid‐base equilibrium between blood and cerebrospinal fluid in acute hypercapnia. J. Appl. Physiol. 27: 271–275, 1969.
3.	Ahmad, H. R., J. Berndt, and H. H. Loeschcke. Bicarbonate exchange between blood, brain extracellular fluid and brain cells at maintained Pco2. In: Acid‐Base Homeostasis of the Brain Extracellular Fluid and the Respiratory Control System, edited by H. H. Loeschcke. Stuttgart, West Germany: Thieme, 1976, p. 19–27.
4.	Ahmad, H. R., H. H. Loeschcke, and H. H. Woidtke. Three compartment model for the bicarbonate exchange of the brain extracellular fluid with blood and cells. In: The Regulation of Respiration During Sleep and Anesthesia, edited by R. S. Fitzgerald, H. Gautier, and S. Lahiri. New York: Plenum, 1978, p. 195–209.
5.	Alksne, J. F., and E. T. Lovings. Functional ultrastructure of the arachnoid villus. Arch. Neurol. 27: 371–377, 1972.
6.	Ames, A., K. Higashi, and F. B. Nesbett. Relation of potassium concentration in choroid plexus fluid to that in plasma. J. Physiol. London 181: 506–515, 1965.
7.	Ames, A., K. Higashi, and F. B. Nesbett. Effects of Pco2, acetazolamide and ouabain on volume and composition of choroid‐plexus fluid. J. Physiol. London 181: 516–524, 1965.
8.	Ames, A., III, M. Sakanoue, and S. Endo. Na, K, Ca, Mg and Cl concentrations in choroid plexus fluid and cisternal fluid compared with plasma ultrafiltrate. J. Neurophysiol. 27: 672–681, 1964.
9.	Besson, J. M., C. D. Woody, P. Aleonard, H. K. Thompson, D. Albe‐Fessard, and W. H. Marshall. Correlations of brain d‐c shifts with changes in cerebral blood flow. Am. J. Physiol. 218: 284–291, 1970.
10.	Bito, L. Z., H. Davson, and J. D. Fenstermacher (editors). The ocular and cerebrospinal fluids. Exp. Eye Res. 25, Suppl.: 1977.
11.	Blayo, M. C., J. Coudert, and J. J. Pocidalo. Comparison of cisternal and lumbar cerebrospinal fluid pH in high altitude natives. Pfluegers Arch. 356: 159–167, 1975.
12.	Blayo, M. C., J. P. Marc‐Vergnes, and J. J. Pocidalo. pH, Pco2 and Po2 of cisternal cerebrospinal fluid in high altitude natives. Respir. Physiol. 19: 298–311, 1973.
13.	Bledsoe, S. W., D. Y. Eng, and T. F. Hornbein. Evidence of active regulation of cerebrospinal fluid acid‐base balance. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51: 369–375, 1981.
14.	Bledsoe, S. W., and T. F. Hornbein. Central chemosensors and the regulation of their chemical environment. In: Regulation of Breathing. Part I, edited by T. F. Hornbein. New York: Dekker, 1981, p. 347–428.
15.	Bledsoe, S. W., and A. H. Mines. Effect of plasma [K+] on the DC potential and on ion distributions between CSF and blood. J. Appl. Physiol. 39: 1012–1016, 1975.
16.	Bleich, H. L., P. M. Berkman, and W. B. Schwartz. The response of cerebrospinal fluid composition to sustained hypercapnia. J. Clin. Invest. 43: 11–16, 1964.
17.	Bourke, R. S., H. L. Gabelnick, and O. Young. Mediated transport of chloride from blood into cerebrospinal fluid. Exp. Brain Res. 10: 17–38, 1970.
18.	Bourke, R. S., and K. M. Nelson. Studies on the site of mediated transport of chloride from blood into cerebrospinal fluid: effects of acetazolamide. J. Neurochem. 19: 1225–1232, 1972.
19.	Bradbury, M. W. B. Magnesium and calcium in cerebrospinal fluid and in the extracellular fluid of brain (Abstract). J. Physiol. London 179: 67P–68P, 1965.
20.	Bradbury, M. W. B. The Concept of a Blood‐Brain Barrier. New York: Wiley, 1979.
21.	Bradbury, M. W. B., and C. R. Kleeman. Stability of the potassium content of cerebrospinal fluid and brain. Am. J. Physiol. 213: 519–528, 1967.
22.	Bradley, R. D., and S. J. G. Semple. A comparison of certain acid‐base characteristics of arterial blood, jugular venous blood and cerebrospinal fluid in man, and the effect on them of some acute and chronic acid‐base disturbances. J. Physiol. London 160: 381–391, 1962.
23.	Brightman, M. W. Morphology of blood‐brain interfaces. Exp. Eye Res. 25, Suppl.: 1–25, 1977.
24.	Brightman, M. W., and T. S. Reese. Junctions between intimately opposed cell membranes in the vertebrate brain. J. Cell Biol. 40: 648–677, 1969.
25.	Brooks, C. McC, F. F. Kao, and B. B. Lloyd (editors). Cerebrospinal Fluid and the Regulation of Ventilation. Oxford, UK: Blackwell, 1966.
26.	Bühlmann, A., W. Scheitlin, and P. H. Rossier. Die Beziehungen zwischen Blut und Liquor cerebrospinalis bei Störungen des Säure‐Basen‐Gleichgewichtes. Schweiz. Med. Wochenschr. 93: 427–432, 1963.
27.	Bureau, M., and P. Bouverot. Blood and CSF acid‐base changes, and rate of ventilatory acclimatization of awake dogs at 3,550 m. Respir. Physiol. 24: 203–216, 1975.
28.	Cameron, I. R., and R. Miller. The effect of plasma potassium concentration and arterial pH on the CSF‐blood potential difference. Bull. Physio.‐Pathol. Respir. 9: 796–800, 1973.
29.	Chazan, J. A., F. M. Appleton, A. M. London, and W. B. Schwartz. Effects of chronic metabolic acid‐base disturbances on the composition of cerebrospinal fluid in the dog. Clin. Sci. 36: 345–358, 1969.
30.	Choma, L., and H. Kazemi. Importance of changes in plasma HCO3− on regulation of CSF HCO3− in respiratory alkalosis. Respir. Physiol. 26: 265–278, 1976.
31.	Clark, J. M., R. D. Sinclair, and B. E. Welch. Rate of acclimatization to chronic hypercapnia in man. In: Underwater Physiology, edited by C. J. Lambertsen. New York: Academic, 1971, p. 399–417.
32.	Cragg, P., L. Patterson, and M. J. Purves. The pH of extracellular fluid in the cat. J. Physiol. London 272: 137–166, 1977.
33.	Crawford, R. D., and J. W. Severinghaus. CSF pH and ventilatory acclimatization to altitude. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 45: 275–283, 1978.
34.	Crone, C. Facilitated transfer of glucose from blood into brain tissue. J. Physiol. London 181: 103–113, 1965.
35.	Cserr, H. F. Physiology of the choroid plexus. Physiol. Rev. 51: 273–311, 1971.
36.	Cserr, H. F. Convention of brain interstitial fluid. In: Microcirculation and Capillary Exchange, edited by A. G. B. Kovách, J. Hamar, and L. Szabo. New York: Pergamon, 1981, p. 337–341.
37.	Cserr, H. F., J. D. Fenstermacher, and V. Fencl (editors). Fluid Environment of the Brain. New York: Academic, 1975.
38.	Davies, D. G. Hydrogen ion homeostasis of the cerebral extracellular fluid. In: Regulation of Ventilation and Gas Exchange, edited by D. G. Davies and C. D. Barnes. New York: Academic, 1978, p. 167–196.
39.	Davson, H. Physiology of the Cerebrospinal Fluid. London: Churchill, 1967.
40.	Dempsey, J. A., and H. V. Forster. Mediation of ventilatory adaptations. Physiol. Rev. 62: 262–346, 1982.
41.	Dempsey, J. A., H. V. Forster, L. W. Chosy, P. G. Hanson, and W. G. Reddan. Regulation of CSF [HCO3−] during long‐term hypoxic hypocapnia in man. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 175–182, 1978.
42.	Dempsey, J. A., H. V. Forster, and G. D. Do Pico. Ventilatory acclimatization to moderate hypoxemia in man. J. Clin. Invest. 53: 1091–1100, 1974.
43.	Edelman, I. S., and J. Leibman. Anatomy of body water and electrolytes. Am. J. Med. 27: 256–277, 1959.
44.	Eisenberg, H. M., and R. L. Suddith. Cerebral vessels have the capacity to transport sodium and potassium. Science 206: 1083–1085, 1979.
45.	Fencl, V. Distribution of H+ and HCO3− in cerebral fluids. In: Ion Homeostasis of the Brain. The Regulation of Hydrogen and Potassium Ion Concentrations in Cerebral Intra‐ and Extracellular Fluids, edited by B. K. Siesjö and S. C. Sørensen. New York: Academic, 1971, p. 175–185.
46.	Fencl, V., J. R. Dmochowski, and A. E. Young. Dynamics of ionic composition of cerebral interstitial fluid in acute metabolic acid‐base disturbances (Abstract). Proc. Int. Congr. Physiol. Sci., 27th, Paris, 1977, vol. 13, p. 223.
47.	Fencl, V., R. A. Gabel, and D. Wolfe. Composition of cerebral fluids in goats adapted to high altitude. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 47: 508–513, 1979.
48.	Fencl, V., T. B. Miller, and J. R. Pappenheimer. Studies on the respiratory response to disturbances of acid‐base balance, with deductions concerning the ionic composition of cerebral interstitial fluid. Am. J. Physiol. 210: 459–472, 1966.
49.	Fencl, V., J. R. Vale, and J. A. Broch. Respiration and cerebral blood flow in metabolic acidosis and alkalosis in humans. J. Appl. Physiol. 27: 67–76, 1969.
50.	Fisher, V. J., and L. C. Christianson. Cerebrospinal fluid acid‐base balance during a changing ventilatory state in man. J. Appl. Physiol. 18: 712–716, 1963.
51.	Folbergrová, J., V. MacMillan, and B. K. Siesjö. The effect of hypercapnic acidosis upon some glycolytic and Krebs cycle‐associated intermediates in the rat brain. J. Neurochem. 19: 2507–2517, 1972.
52.	Forster, H. V., G. E. Bisgard, B. Rasmussen, J. A. Orr, D. D. Buss, and M. Manohar. Ventilatory control in peripheral chemoreceptor‐denervated ponies during chronic hypoxemia. J. Appl. Physiol. 41: 878–885, 1976.
53.	Forster, H. V., J. A. Dempsey, and L. W. Chosy. Incomplete compensation of CSF [H+] in man during acclimatization to high altitude (4,300 m). J. Appl. Physiol. 38: 1067–1072, 1975.
54.	Géraud, J., A. Rascol, A. Bes, B. Guiraud, and G. Géraud. Le liquide céphalo‐rachidien dans les perturbations de la balance acido‐basique plasmatique. Nouv. Presse Med. 2: 1785–1790, 1973.
55.	Giacobini, E. Cytochemical study of the localization of carbonic anhydrase in the nervous system. J. Neurochem. 9: 169–177, 1962.
56.	Goodrich, C. Effect of chronic acidosis and alkalosis on rat CSF‐blood potential (Abstract). Physiologist 8: 178, 1965.
57.	Granholm, L., L. Lukjanova, and B. K. Siesjö. The effect of marked hyperventilation upon tissue levels of NADH, lactate, pyruvate, phosphocreatine, and adenosine phosphates of rat brain. Acta Physiol. Scand. 77: 179–180, 1969.
58.	Granholm, L., and U. Pontén. The in vivo CO2 buffer curve of the intracellular space of cat cerebral cortex. Acta Neurol. Scand. 45: 493–501, 1969.
59.	Granholm, L., and B. K. Siesjö. The effects of hypercapnia and hypocapnia upon the cerebrospinal fluid lactate and pyruvate concentrations and upon the lactate, pyruvate, ATP, ADP, phosphocreatine and creatine concentrations of cat brain tissue. Acta Physiol. Scand. 75: 257–266, 1969.
60.	Hasan, F. M., and H. Kazemi. Dual contribution theory of regulation of CSF HCO3− in respiratory acidosis. J. Appl. Physiol. 40: 559–567, 1976.
61.	Held, D., V. Fencl, and J. R. Pappenheimer. Electrical potential of cerebrospinal fluid. J. Neurophysiol. 27: 942–959, 1964.
62.	Heuser, D., J. Astrup, N. A. Lassen, and E. Betz. Brain carbonic acid acidosis after acetazolamide. Acta Physiol. Scand. 93: 385–390, 1975.
63.	Hjelle, J. T., J. Baird‐Lambert, G. Cardinale, S. Spector, and S. Udenfriend. Isolated microvessels: the blood‐brain barrier in vitro. Proc. Natl. Acad. Sci. USA 75: 4544–4548, 1978.
64.	Hornbein, T. F., and E. G. Pavlin. Distribution of H+ and HCO3− between CSF and blood during respiratory alkalosis in dogs. Am. J. Physiol. 228: 1149–1154, 1975.
65.	Hornbein, T. F., and S. C. Sørensen. d‐c Potential difference between different cerebrospinal fluid sites and blood in dogs. Am. J. Physiol. 223: 415–418, 1972.
66.	Huang, C. T., and H. A. Lyons. The maintenance of acid‐base balance between cerebrospinal fluid and arterial blood in patients with chronic respiratory disorders. Clin. Sci. 31: 273–284, 1966.
67.	Husted, R. F., and D. J. Reed. Regulation of cerebrospinal fluid bicarbonate by the cat choroid plexus. J. Physiol. London 267: 411–428, 1977.
68.	Jaikin, A., and A. Agrest. Cerebrospinal fluid glutamine concentration in patients with chronic hypercapnia. Clin. Sci. 36: 11–14, 1969.
69.	Javaheri, S., A. Clendening, N. Papadakis, and J. S. Brody. Changes in brain surface pH during acute isocapnic metabolic acidosis and alkalosis. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51: 276–281, 1981.
70.	Javaheri, S., and H. Kazemi. Electrolyte composition of cerebrospinal fluid in acute acid‐base disorders. Respir. Physiol. 45: 141–151, 1981.
71.	Javaheri, S., E. Nardell, and H. Kazemi. Role of Pco2 as determinant of CSF [HCO3−] in metabolic acidosis. Respir. Physiol. 36: 155–156, 1979.
72.	Kao, F. F., and H. H. Loeschcke. Bestandspotential im Gebiete der Liquorräume. Naturwissenschaften 52: 562–563, 1965.
73.	Katzman, R., and H. M. Pappius. Brain Electrolytes and Fluid Metabolism. Baltimore, MD: Williams & Wilkins, 1973.
74.	Kazemi, H., and L. Choma. H+ transport from CNS in hypercapnia and regulation of CSF [HCO3−]. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 42: 667–672, 1977.
75.	Kazemi, H., and S. Javaheri. Interaction between Pco2 and plasma [HCO3−] in regulation of CSF [HCO3−] in respiratory alkalosis and metabolic acidosis. In: The Regulation of Respiration During Sleep and Anesthesia, edited by R. S. Fitzgerald, H. Gautier, and S. Lahiri. New York: Plenum, 1978, p. 173–183.
76.	Kazemi, H., and J. C. Mithoefer. CO2 dissociation curve of dog brain. Am. J. Physiol. 205: 598–600, 1963.
77.	Kazemi, H., N. S. Shore, V. E. Shih, and D. C. Shannon. Brain organic buffers in respiratory acidosis and alkalosis. J. Appl. Physiol. 34: 478–482, 1973.
78.	Kazemi, H., L. M. Valenca, and D. C. Shannon. Brain and cerebrospinal fluid lactate concentration in respiratory acidosis and alkalosis. Respir. Physiol. 6: 178–186, 1969.
79.	Kazemi, H., J. Weyne, F. Van Leuven, and I. Leusen. The CSF HCO3− increase in hypercapnia: relationship to HCO3−, glutamate, glutamine and NH3 in brain. Respir. Physiol. 28: 387–401, 1976.
80.	Kelley, M. A., and H. Kazemi. Role of ammonia as a buffer in the central nervous system. Respir. Physiol. 22: 345–359, 1974.
81.	Kibler, R. F., R. P. O'Neill, and E. D. Robin. Intracellular acid‐base relations of dog brain with reference to the brain extracellular volume. J. Clin. Invest. 43: 431–443, 1964.
82.	Kjällquist, Å. The CSF/blood potential in sustained acid‐base changes in the rat. With calculations of electrochemical potential differences for H+ and HCO3−. Acta Physiol. Scand. 78: 85–93, 1970.
83.	Kjällquist, Å., M. Nardini, and B. K. Siesjö. The regulation of extra‐ and intracellular acid‐base parameters in the rat brain during hyper‐ and hypocapnia. Acta Neurol. Scand. 76: 485–494, 1969.
84.	Kjällquist, Å., and B. K. Siesjö. The CSF/blood potential in sustained acidosis and alkalosis in the rat. Acta Physiol. Scand. 71: 255–256, 1967.
85.	Leusen, I. R. Chemosensitivity of the respiratory center. Influence of CO2 in the cerebral ventricles on respiration. Am. J. Physiol. 176: 39–44, 1954.
86.	Leusen, I. R. Chemosensitivity of the respiratory center. Influence of changes in the H+ and total buffer concentrations in the cerebral ventricles on respiration. Am. J. Physiol. 176: 45–51, 1954.
87.	Leusen, I. Aspects of the acid‐base balance between blood and cerebrospinal fluid. In: Cerebrospinal Fluid and the Regulation of Ventilation, edited by C. McC. Brooks, F. F. Kao, and B. B. Lloyd. Oxford, UK: Blackwell, 1965, p. 55–89.
88.	Leusen, I. Regulation of cerebrospinal fluid composition with reference to breathing. Physiol. Rev. 52: 1–56, 1972.
89.	Loeschcke, H. H. Über Bestandspotentiale im Gebiete der Medulla oblongata. Pfluegers Arch. Gesamte Physiol. Menschen Tiere 262: 517–531, 1956.
90.	Loeschcke, H. H. Über den Einfluss von CO2 auf die Bestandspotentiale der Hirnhäute. Pfluegers Arch. Gesamte Physiol. Menschen Tiere 262: 532–536, 1956.
91.	Loeschcke, H. H. DC potentials between CSF and blood. In: Ion Homeostasis of the Brain. The Regulation of Hydrogen and Potassium Concentrations in Cerebral Intra‐ and Extracellular Fluids, edited by B. K. Siesjö and S. C. Sørensen. New York: Academic, 1971, p. 77–96.
92.	Loeschcke, H. H. Der Säure‐Basenstatus des Liquor cerebrospinalis und seine Regulation durch die Lungenventilation. Klin. Wochenschr. 50: 581–593, 1972.
93.	Loeschcke, H. H. (editor). Acid Base Homeostasis of the Brain Extracellular Fluid and the Respiratory Control System. Stuttgart, West Germany: Thieme, 1976.
94.	Loeschcke, H. H., and H. R. Ahmad. Transients and steady‐state chloride‐bicarbonate relationships of brain extra‐cellular fluid. In: Biophysics and Physiology of Carbon Dioxide, edited by C. Bauer, G. Gros, and H. Bartels. New York: Springer‐Verlag, 1980, p. 439–448.
95.	Maren, T. H. Carbonic anhydrase: chemistry, physiology and inhibition. Physiol. Rev. 47: 595–781, 1967.
96.	Maren, T. H. Bicarbonate formation in cerebrospinal fluid: role in sodium transport and pH regulation. Am. J. Physiol. 222: 885–899, 1972.
97.	Maren, T. H. Effect of varying CO2 equilibria on rates of HCO3− formation in cerebrospinal fluid (Editorial review). J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 47: 471–477, 1979.
98.	Maren, T. H., and L. E. Broder. The role of carbonic anhydrase in anion secretion into cerebrospinal fluid. J. Pharmacol. Exp. Ther. 172: 197–202, 1970.
99.	Marks, C. E., Jr., R. M. Goldring, J. J. Vecchione, and E. E. Gordon. Cerebrospinal fluid acid‐base relationships in ketoacidosis and lactic acidosis. J. Appl. Physiol. 35: 813–819, 1973.
100.	McIlwain, H., and H. S. Bachelard. Biochemistry and the Central Nervous System. London: Churchill, 1971.
101.	Messeter, K., and B. K. Siesjö. Regulation of intracellular pH in the rat brain in chronic hypercapnia. Acta Physiol. Scand. 79: 136–138, 1970.
102.	Messeter, K., and B. K. Siesjö. Electrochemical gradients for H+ and HCO3− between blood and CSF during sustained acid‐base changes. In: Ion Homeostasis of the Brain. The Regulation of Hydrogen and Potassium Ion Concentrations in Cerebral Intra‐ and Extracellular Fluids, edited by B. K. Siesjö and S. C. Sørensen. New York: Academic, 1971, p. 190–200.
103.	Mines, A. H., C. G. Morril, and S. C. Sørensen. The effect of isocarbic metabolic acidosis in blood on [H+] and [HCO3−] in CSF, with deductions about the regulation of an active transport of H+/HCO3− between blood and CSF. Acta Physiol. Scand. 81: 234–245, 1971.
104.	Mitchell, R. A. Cerebrospinal fluid and the regulation of respiration. In: Advances in Respiratory Physiology, edited by C. G. Caro. London: Arnold, 1966, p. 1–47.
105.	Mitchell, R. A., C. T. Carman, J. W. Severinghaus, B. W. Richardson, M. M. Singer, and S. Shnider. Stability of cerebrospinal fluid pH in chronic acid‐base disturbances in blood. J. Appl. Physiol. 20: 443–452, 1965.
106.	Monroe, C. B., and H. Kazemi. Effect of changes in plasma bicarbonate level on CSF bicarbonate in respiratory acidosis. Respir. Physiol. 17: 386–393, 1973.
107.	Mottschall, H. J., and H. H. Loeschcke. Das transmeningeale Potential der Katze bei Änderung des CO2‐Druckes und der H+ Ionenkonzentration. Pfluegers Arch. Gesamte Physiol. Menschen Tiere 277: 662–670, 1963.
108.	Nattie, E. E., and L. Romer. CSF HCO3− regulation in isosmotic conditions: the role of brain Pco2 and plasma HCO3−. Respir. Physiol. 33: 177–198, 1978.
109.	Nattie, E. E., and L. Romer. The role of chloride and other anions in cerebrospinal fluid bicarbonate regulation. In: The Regulation of Respiration During Sleep and Anesthesia, edited by R. S. Fitzgerald, H. Gautier, and S. Lahiri. New York: Plenum, 1978, p. 211–218.
110.	Nattie, E. E., and S. M. Tenney. Effect of potassium depletion on cerebrospinal fluid bicarbonate homeostasis. Am. J. Physiol. 231: 579–587, 1976.
111.	Nemoto, E. M., and J. W. Severinghaus. Stereospecific permeability of rat blood‐brain barrier to lactic acid. Stroke 5: 81–84, 1974.
112.	Oldendorf, W. H. Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection. Am. J. Physiol. 221: 1629–1639, 1971.
113.	Oldendorf, W. H. Carrier mediated blood‐brain barrier transport of short‐chain monocarboxylic organic acids. Am. J. Physiol. 224: 1450–1453, 1973.
114.	Oldendorf, W. H. The blood‐brain barrier. Exp. Eye Res., 25, Suppl.: 177–190, 1977.
115.	Orr, J. A., G. E. Bisgard, H. V. Forster, D. D. Buss, J. A. Dempsey, and J. A. Will. Cerebrospinal fluid alkalosis during high‐altitude sojourn in unanesthetized ponies. Respir. Physiol. 25: 23–37, 1975.
116.	Pannier, J. L., and I. Leusen. Circulation to the brain of the rat during acute and prolonged respiratory changes in the acid‐base balance. Pfluegers Arch. 338: 347–359, 1973.
117.	Pannier, J. L., J. Weyne, and I. Leusen. The CSF/pH potential and the regulation of the bicarbonate concentration of CSF during acidosis in the cat. Life Sci. 10: 287–300, 1971.
118.	Pappenheimer, J. R. The ionic composition of cerebral extracellular fluid and its relation to control of breathing. Harvey Lect. 61: 71–94, 1965‐1966.
119.	Pappenheimer, J. R. Transport of HCO3− between brain and blood. In: Capillary Permeability, edited by C. Crone and N. A. Lassen. New York: Academic, 1970, p. 454–458.
120.	Pappenheimer, J. R., V. Fencl, S. R. Heisey, and D. Held. Role of cerebral fluids in control of respiration as studied in unanesthetized goats. Am. J. Physiol. 208: 436–450, 1965.
121.	Pauli, H. G., C. Vorburger, and F. Reubi. Chronic derangements of cerebrospinal fluid acid‐base components in man. J. Appl. Physiol. 17: 993–998, 1962.
122.	Pavlin, E. G., and T. F. Hornbein. Distribution of H+ and HCO3− between CSF and blood during metabolic acidosis in dogs. Am. J. Physiol. 228: 1134–1140, 1975.
123.	Pavlin, E. G., and T. F. Hornbein. Distribution of H+ and HCO3− between CSF and blood during metabolic alkalosis in dogs. Am. J. Physiol. 228: 1141–1144, 1975.
124.	Pavlin, E. G., and T. F. Hornbein. Distribution of H+ and HCO3− between CSF and blood during respiratory acidosis in dogs. Am. J. Physiol. 228: 1145–1148, 1975.
125.	Pelligrino, D., and J. A. Dempsey. Dependence of CSF on plasma bicarbonate during hypocapnia and hypoxemic hypocapnia. Respir. Physiol. 26: 11–26, 1976.
126.	Pelligrino, D. A., T. I. Musch, and J. A. Dempsey. Interregional differences in brain intracellular pH and water compartmentation during acute normoxic and hypoxic hypocapnia in anesthetized dogs. Brain Res. 214: 387–404, 1981.
127.	Plum, F., and J. B. Posner. Blood and cerebrospinal fluid lactate during hyperventilation. Am. J. Physiol. 212: 864–870, 1967.
128.	Plum, F., and J. B. Posner. Inhomogeneity of cisternal and lumbar CSF acid‐base balance during acute metabolic alterations. Scand. J. Clin. Lab. Invest. Suppl. 102: 1B, 1968.
129.	Plum, F., and R. W. Price. Acid‐base balance in cisternal and lumbar cerebrospinal fluid in hospital patients. N. Engl. J. Med. 289: 1346–1351, 1973.
130.	Pontén, U. Acid‐base changes in rat brain tissue during acute respiratory acidosis and baseosis. Acta Physiol. Scand. 68: 152–163, 1966.
131.	Pontén, U., and B. K. Siesjö. Gradients of CO2 tension in the brain. Acta Physiol. Scand. 67: 129–140, 1966.
132.	Pontén, U., and B. K. Siesjö. Acid‐base relationship in arterial blood and cerebrospinal fluid of the unanesthetized rat. Acta Physiol. Scand. 71: 89–95, 1967.
133.	Posner, J. B., and F. Plum. Independence of blood and cerebrospinal fluid lactate. Arch. Neurol. 16: 492–496, 1967.
134.	Posner, J. B., A. G. Swanson, and F. Plum. Acid‐base balance in cerebrospinal fluid. Arch. Neurol. 12: 479–496, 1965.
135.	Rall, D. P., W. W. Oppelt, and C. S. Patlak. Extracellular space of brain as determined by diffusion of inulin from the ventricular system. Life Sci. 2: 43–48, 1962.
136.	Rapoport, S. I. Cortical pH and the blood‐brain barrier. J. Physiol. London 170: 238–249, 1964.
137.	Rapoport, S. I. Blood‐Brain Barrier in Physiology and Medicine. New York: Raven, 1976.
138.	Rapoport, S. I., and H. K. Thompson. Effect of intravenous NH4Cl and NaHCO3 on the pH of the brain surface, as related to respiration and the blood‐brain barrier. Exp. Neurol. 42: 320–331, 1974.
139.	Reese, T. S., and M. J. Karnovsky. Fine structural localization of a blood‐brain barrier to exogenous peroxidase. J. Cell Biol. 34: 207–217, 1967.
140.	Robin, E. D., R. D. Whaley, C. H. Crump, A. G. Bickelmann, and D. M. Travis. Acid‐base relations between spinal fluid and arterial blood with special reference to control of ventilation. J. Appl. Physiol. 13: 385–392, 1958.
141.	Rosenberg, G. A., W. T. Kyner, and E. Estrada. Bulk flow of brain interstitial fluid under normal and hyperosmolar conditions. Am. J. Physiol. 238 (Renal Fluid Electrolyte Physiol. 7): F42–F49, 1980.
142.	Saunier, C., M.‐C. Aug‐Laxenaire, M. Schibi, and P. Sadoul. Acid‐base and electrolyte equilibrium of arterial blood and cerebrospinal fluid in respiratory insufficiency. Respiration 26: 81–101, 1969.
143.	Saunier, C., E. Reichart, M. Schibi, M.‐C. Aug, and Y. Rouch. l' équilibre acido‐basique du liquide céphalo‐rachidien au cours de l'hypercapnie. Bull. Physio.‐Pathol. Respir. 1: 181–202, 1965.
144.	Scheinberg, P., I. Blackburn, M. Saslaw, M. Rich, and G. Baum. Cerebral circulation and metabolism in pulmonary emphysema and fibrosis with observations on the effects of mild exercise. J. Clin. Invest. 32: 720–728, 1953.
145.	Schöne, H., and H. H. Loeschcke. Bestandspotentiale am Plexus chorioideus des 4. Ventrikels von Katze und Kaninchen in vitro. Pfluegers Arch. 306: 195–209, 1969.
146.	Schwab, M. Das Saure‐Basen‐Gleichgewicht im arteriellen Blut und Liquor cerebrospinalis bei Herzinsuffizienz und Cor pulmonale und seine Beeinflussung durch Carboanhydrase‐Hemmung. Klin. Wochenschr. 40: 1233–1245, 1962.
147.	Severinghaus, J. W. Electrochemical gradients for hydrogen and bicarbonate ions across the blood‐CSF barrier in response to acid‐base balance changes. In: Cerebrospinal Fluid and the Regulation of Ventilation, edited by C. McC. Brooks, F. F. Kao, and B. B. Lloyd. Oxford, UK: Blackwell, 1965, p. 247–258.
148.	Severinghaus, J. W., and A. Carcelen B. Cerebrospinal fluid in man native to high altitude. J. Appl. Physiol. 19: 319–321, 1964.
149.	Severinghaus, J. W., H. Chiodi, E. I. Eger II., B. Brandstater, and T. F. Hornbein. Cerebral blood flow in man at high altitude. Role of cerebrospinal fluid pH in normalization of flow in chronic hypocapnia. Circ. Res. 19: 274–281, 1966.
150.	Severinghaus, J. W., R. A. Mitchell, B. W. Richardson, and M. M. Singer. Respiratory control at high altitude suggesting active transport regulation of CSF pH. J. Appl. Physiol. 18: 1155–1166, 1963.
151.	Siesjö, B. K. The bicarbonate/carbonic acid buffer system of the cerebral cortex of the cat as studied in tissue homogenates. I. The amount of carbon dioxide bound at different carbon dioxide tensions. Acta Neurol. Scand. 38: 98–120, 1962.
152.	Siesjö, B. K. The regulation of cerebrospinal fluid pH. Kidney Int. 1: 360–374, 1972.
153.	Siesjö, B. K. Brain Energy Metabolism. New York: Wiley, 1978.
154.	Siesjö, B. K., and Å. Kjällquist. A new theory for the regulation of the extracellular pH in the brain. Scand. J. Clin. Lab. Invest. 24: 1–9, 1969.
155.	Siesjö, B. K., and K. Messeter. Factors determining intracellular pH. In: Ion Homeostasis of the Brain. The Regulation of Hydrogen and Potassium Ion Concentration in Cerebral Intra‐ and Extracellular Fluids, edited by B. K. Siesjö and S. C. Sørensen. New York: Academic, 1971, p. 244–262.
156.	Siesjö, B. K., and U. Pontén. Acid‐base changes in the brain in nonrespiratory acidosis and alkalosis. Exp. Brain Res. 2: 176–190, 1966.
157.	Siesjö, B. K., and S. C. Sørensen (editors). Ion Homeostasis of the Brain. The Regulation of Hydrogen and Potassium Ion Concentrations in Cerebral Intra‐ and Extracellular Fluids. New York: Academic, 1971.
158.	Sigaard‐Andersen, O. The Acid‐Base Status of the Blood. Copenhagen: Munksgaard, 1963.
159.	Singer, R. B., and A. B. Hastings. An improved clinical method for the estimation of disturbances of the acid‐base balance of human blood. Medicine Baltimore 27: 223–242, 1948.
160.	Skinhøj, E. Regulation of cerebral blood flow as a single function of the interstitial pH in the brain. Acta Neurol. Scand. 42: 604–607, 1966.
161.	Sørensen, S. C. Factors regulating [H+] and [HCO3−] in brain extracellular fluid. In: Ion Homeostasis of the Brain. The Regulation of Hydrogen and Potassium Ion Concentration in Cerebral Intra‐ and Extracellular Fluids, edited by B. K. Siesjö and S. C. Sørensen. New York: Academic, 1971, p. 206–217.
162.	Sørensen, E., J. Oleson, J. Rask‐Madsen, and H. Rask‐Andersen. The electrical potential difference and impedance between CSF and blood in unanesthetized man. Scand. J. Clin. Lab. Invest. 38: 203–207, 1978.
163.	Sørensen, S. C., and J. W. Severinghaus. Effects of cerebral acidosis on the CSF‐blood potential difference. Am. J. Physiol. 219: 68–71, 1970.
164.	Stewart, P. A. Independent and dependent variables of acid‐base control. Respir. Physiol. 33: 9–26, 1978.
165.	Stewart, P. A. How to Understand Acid‐Base Balance. A Quantitative Acid‐Base Primer for Biology and Medicine. New York: Elsevier, 1981.
166.	Tschirgi, R. D., and J. L. Taylor. Slowly changing bioelectric potentials associated with the blood‐brain barrier. Am. J. Physiol. 195: 7–22, 1958.
167.	Van Heijst, A. N. P., A. H. J. Maas, and B. F. Visser. l'équilibre acido‐basique dans le sang et le liquide céphalo‐rachidien dans l'hypercapnie chronique. Bull. Physio.‐Pathol. Respir. 1: 169–179, 1965.
168.	Van Heijst, A. N. P., A. H. J. Maas, and B. F. Visser. Comparison of the acid‐base balance in cisternal and lumbar cerebrospinal fluid. Pfluegers Arch. Gesamte Physiol. Menschen Tiere 287: 242–246, 1966.
169.	Vogh, B. P., and T. H. Maren. Sodium, chloride, and bicarbonate movement from plasma to cerebrospinal fluid in cats. Am. J. Physiol. 228: 673–683, 1975.
170.	Weiskopf, R. B., R. A. Gabel, and V. Fencl. Alkaline shift in lumbar and intracranial CSF in man after 5 days at high altitude. J. Appl. Physiol. 41: 93–97, 1976.
171.	Welch, K., and V. Friedman. The cerebrospinal fluid valves. Brain 83: 454–469, 1960.
172.	Welch, K., and K. Sadler. Electrical potentials of the choroid plexus of the rabbit. J. Neurosurg. 22: 344–351, 1965.
173.	Weyne, J., G. Demeester, and I. Leusen. Bicarbonate and chloride shifts in rat brain during acute and prolonged respiratory acid‐base changes. Arch. Int. Physiol. Biochim. 76: 415–433, 1968.
174.	Weyne, J., and I. Leusen. Bicarbonate, chloride and lactate in brain during acid‐base alterations. In: Ion Homeostasis of the Brain. The Regulation of Hydrogen and Potassium Ion Concentrations in Cerebral Intra‐ and Extracellular Fluids, edited by B. K. Siesjö and S. C. Sørensen. New York: Academic, 1971, p. 352–374.
175.	Weyne, J., and I. Leusen. Lactate in cerebrospinal fluid in relation to brain and blood. In: Fluid Environment of the Brain, edited by H. F. Cserr, J. D. Fenstermacher, and V. Fencl. New York: Academic, 1975, p. 255–276.
176.	Weyne, J., F. Van Leuven, H. Kazemi, and I. Leusen. Selected brain amino acids and ammonium during chronic hypercapnia in conscious rats. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 333–339, 1978.
177.	Wichser, J., and H. Kazemi. CSF bicarbonate regulation in respiratory acidosis and alkalosis. J. Appl. Physiol. 38: 504–512, 1975.
178.	Winterstein, H. The actions of substances introduced into the cerebrospinal fluid and the problem of intracranial chemoreceptors. Pharmacol. Rev. 13: 71–107, 1961.
179.	Wood, J. H. Neurology of Cerebrospinal Fluid I. New York: Plenum, 1980.
180.	Woodbury, J. W. Regulation of pH. In: Physiology and Biophysics (19th ed.), edited by T. C. Ruch and H. D. Patton. Philadelphia, PA: Saunders, 1966, p. 899–934.
181.	Woodbury, J. W. An epilogue. A hypothetical model for CSF formation and blood‐brain barrier function. In: Ion Homeostasis of the Brain. The Regulation of Hydrogen and Potassium Ion Concentrations in Cerebral Intra‐ and Extracellular Fluids, edited by B. K. Siesjö and S. C. Sørensen. New York: Academic, 1971, p. 465–471.
182.	Woody, C. D., W. H. Marshall, J. M. Besson, H. K. Thompson, P. Aleonard, and D. Albe‐Fessard. Brain potential shift with respiratory acidosis in the cat and monkey. Am. J. Physiol. 218: 275–283, 1970.
183.	Wright, E. M. Mechanisms of ion transport across the choroid plexus. J. Physiol. London 226: 545–571, 1972.
184.	Wright, E. M. Transport processes in the formation of the cerebrospinal fluid. Rev. Physiol. Biochem. Pharmacol. 83: 1–34, 1978.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title:	Acid‐Base Balance in Cerebral Fluids
* Name:
* E-mail:
* Note:

How to Cite

Vladimir Fencl. Acid‐Base Balance in Cerebral Fluids. Compr Physiol 2011, Supplement 11: Handbook of Physiology, The Respiratory System, Control of Breathing: 115-140. First published in print 1986. doi: 10.1002/cphy.cp030204

Collections

Free Featured Articles