Bench-to-bedside review: Chloride in critical illness

Nor'azim Mohd Yunos, Rinaldo Bellomo, David Story, John Kellum, Nor'azim Mohd Yunos, Rinaldo Bellomo, David Story, John Kellum

Abstract

Chloride is the principal anion in the extracellular fluid and is the second main contributor to plasma tonicity. Its concentration is frequently abnormal in intensive care unit patients, often as a consequence of fluid therapy. Yet chloride has received less attention than any other ion in the critical care literature. New insights into its physiological roles have emerged together with progress in understanding the structures and functions of chloride channels. In clinical practice, interest in a physicochemical approach to acid-base physiology has directed renewed attention to chloride as a major determinant of acid-base status. It has also indirectly helped to generate interest in other possible effects of disorders of chloraemia. The present review summarizes key aspects of chloride physiology, including its channels, as well as the clinical relevance of disorders of chloraemia. The paper also highlights current knowledge on the impact of different types of intravenous fluids on chloride concentration and the potential effects of such changes on organ physiology. Finally, the review examines the potential intensive care unit practice implications of a better understanding of chloride.

Figures

Figure 1
Figure 1
Chloride distribution in the major body fluid compartments.
Figure 2
Figure 2
Integration of proximal convoluted tubule chloride transport mechanisms with strong ion difference and partial pressure. Chloride is reabsorbed from passive paracellular transport, conductance and active coupled transport at both apical and basolateral membranes. The strong ion difference (SID) in the plasma, together with the partial pressure of carbon dioxide (PCO2), regulates these transport activities and determines the hydrogen ion concentration. KCC, K+Cl- co-transporter; NHE, Na+H+ exchanger; SLC26A6, solute carrier 26A6; SLC4A4, solute carrier 4A4.

References

    1. Ganong WF. Review of Medical Physiology. 22. New York: McGraw Hill; 2005.
    1. PubMed.
    1. Kellum JA. Acid-base physiology in the post-Copernican area. Curr Opin Crit Care. 1999;5:429–435. doi: 10.1097/00075198-199912000-00003.
    1. Cushing H. Concerning the poisonous effect of pure sodium chloride solutions upon nerve-muscle preparation. Am J Physiol. 1901;6:77–90.
    1. Odaira T. The influence of some neutral salt solutions, intravenously administered, on the reserve alkali of the blood. Tohoku J Exp Med. 1923;4:523–526. doi: 10.1620/tjem.4.523.
    1. Shires GT, Holman J. Dilution acidosis. Ann Intern Med. 1948;28:557–559.
    1. Black DAK. Body fluid depletion. Lancet. 1953;261:305–311. doi: 10.1016/S0140-6736(53)90991-X.
    1. McFarlane C, Lee A. A comparison of Plasmalyte 148 and 0.9% saline for intra-operative fluid replacement. Anaesthesia. 1994;49:779–781. doi: 10.1111/j.1365-2044.1994.tb03311.x.
    1. Scheingraber S, Rehm M, Sehmisch C, Finsterer U. Rapid saline infusion produces hyperchloraemic acidosis in patients undergoing gynecologic surgery. Anesthesiology. 1999;90:1265–1270. doi: 10.1097/00000542-199905000-00007.
    1. Waters JH, Miller LR, Clack S, Kim JV. Cause of metabolic acidosis in prolonged surgery. Crit Care Med. 1999;27:2142–2146. doi: 10.1097/00003246-199910000-00011.
    1. Liskaser FJ, Bellomo R, Hayhoe M, Story D, Poustie S, Smith B, Letis A, Bennett M. The role of pump prime in the etiology and pathogenesis of cardiopulmonary bypass-associated acidosis. Anesthesiology. 2000;93:1170–1173. doi: 10.1097/00000542-200011000-00006.
    1. Rehm M, Orth V, Scheingraber S, Kreimeier U, Brechtelsbauer H, Finsterer U. Acid-base changes due to 5% albumin versus 6% hydroxyethylstarch solution in patients undergoing acute normovolemic hemodilution: a randomized prospective study. Anesthesiology. 2000;93:1174–1183. doi: 10.1097/00000542-200011000-00007.
    1. Waters JH, Bernstein CA. Dilutional acidosis following hetastarch or albumin in healthy volunteers. Anesthesiology. 2000;93:1184–1187. doi: 10.1097/00000542-200011000-00008.
    1. Wilkes NJ, Woolf R, Mutch M, Mallett SV, Peachey T, Stephens R, Mythen MG. The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients. Anesth Analg. 2001;93:811–816. doi: 10.1097/00000539-200110000-00003.
    1. Waters JH, Gottlieb A, Schoenwald P, Popovic MJ, Sprung J, Nelson DR. Normal saline versus lactated Ringer's solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm repair: an outcome study. Anesth Analg. 2001;93:817–822. doi: 10.1097/00000539-200110000-00004.
    1. Stewart PA. How to Understand Acid-Base. A Quantitative Primer for Biology and Medicine. New York: Elsevier; 1981.
    1. Stewart PA. Modern quantitative acid-base chemistry. Can J Physiol Pharmacol. 1983;61:1444–1461.
    1. Klemtz K, Ho L, Bellomo R. Daily intravenous chloride load and the acid-base and biochemical status of intensive care unit patients. J Pharm Pract Res. 2008;38:296–299.
    1. Jentsch TJ. Chloride channels are different. Nature. 2002;415:276–277. doi: 10.1038/415276a.
    1. Dutzler R, Campbell EB, Cadene M, Chait BT, MacKinnon R. X-ray structure of a ClC channel at 3.0 Å reveals the molecular basis of anion selectivity. Nature. 2002;415:287–294. doi: 10.1038/415287a.
    1. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002;82:503–568.
    1. Food and Nutrition Board, Institute of Medicine of the National Academies. Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate. Washington, DC: National Academies Press; 2004.
    1. Schultz SG. In: Essential Medical Physiology. 3. Johnson LR, Byrne JH, editor. San Diego: Academic Press; 2003. The internal environment; pp. 4–6.
    1. Koch SM, Taylor RW. Chloride ion in intensive care medicine. Crit Care Med. 1992;20:227–240. doi: 10.1097/00003246-199202000-00012.
    1. Morimatsu H, Rocktaschel J, Bellomo R, Uchino S, Goldsmith D, Gutteridge G. Comparison of point-of-care versus central laboratory measurement of electrolyte concentrations on calculations of the anion gap and the strong ion difference. Anesthesiology. 2003;98:1077–1084. doi: 10.1097/00000542-200305000-00009.
    1. Story D, Morimatsu H, Egi M, Bellomo R. The effect of albumin concentration on plasma sodium and chloride measurements in critically ill patients. Anesth Analg. 2007;104:893–897. doi: 10.1213/01.ane.0000258015.87381.61.
    1. Figge J, Jabor A, Kazda A, Fencl V. Anion gap and hypoalbuminemia. Crit Care Med. 1998;26:1807–1810.
    1. Kellum JA, Kramer DJ, Pinsky MR. Strong ion gap: a methodology for exploring unexplained anions. J Crit Care. 1995;10:51–55. doi: 10.1016/0883-9441(95)90016-0.
    1. Story D, Morimatsu H, Bellomo R. Strong-ions, weak-acids, and base-excess: a simplified Fencl-Stewart approach to clinical acid-base disorders. Br J Anaesth. 2004;92:54–60. doi: 10.1093/bja/aeh018.
    1. Boldt J, Schollhorn T, Munchbach J, Pabsdorf M. A total balanced volume replacement strategy using a new balanced hydroxyethyl starch preparation (6% HES 130/0.42) in patients undergoing major abdominal surgery. Eur J Anaesthesiol. 2007;24:267–275. doi: 10.1017/S0265021506001682.
    1. Story DA, Morimatsu H, Bellomo R. Hyperchloraemic acidosis in the critically ill: one of the strong-ion acidoses? Anesth Analg. 2006;103:144–148. doi: 10.1213/01.ane.0000221449.67354.52.
    1. Rocktaeschel J, Morimatsu H, Uchino S, Bellomo R. Unmeasured anions in critically ill patients: can they predict mortality? Crit Care Med. 2003;31:2131–2136. doi: 10.1097/01.CCM.0000079819.27515.8E.
    1. Antinoni B, Piva S, Paltenghi M, Candiani A, Latronico N. The early phase of critical illness is a progressive acidic state due to unmeasured anions. Eur J Anaesthesiol. 2008;25:566–572. doi: 10.1017/S0265021508003669.
    1. Story DA. Hyperchloraemic acidosis: another misnomer? Crit Care Resusc. 2004;6:188–192.
    1. Alfaro V, Torras R, Ibanez J, Palacios L. A physical-chemical analysis of the acid-base response to chronic obstructive pulmonary disease. Can J Physiol Pharmacol. 1996;74:1229–1235. doi: 10.1139/cjpp-74-11-1229.
    1. Levitin H, Branscome W, Epstein FH. The pathogenesis of hypochloremia in respiratory acidosis. J Clin Invest. 1958;37:1667–1675. doi: 10.1172/JCI103758.
    1. Verkman AS, Galietta JV. Chloride channels as drug targets. Nat Rev Drug Discov. 2009;8:153–171. doi: 10.1038/nrd2780.
    1. Pusch M. Myotonia caused by mutations in the muscle chloride channel gene CLCN1. Hum Mut. 2002;19:423–434. doi: 10.1002/humu.10063.
    1. Haug K, Warnstedt M, Alekov AK, Sander T, Ramirez A, Poser B, Maljevic S, Hebeisen S, Kubisch C, Rebstock J, Horvath S, Hallman K, Dullinger JS, Rau B, Haverkamp F, Beyenburg S, Schulz H, Janz D, Giese B, Müller-Newen G, Propping P, Elger CE, Fahlke C, Lerche H, Heils A. Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies. Nat Genet. 2003;33:527–532. doi: 10.1038/ng1121.
    1. Crowell MD, Harris LA, DiBaise JK, Olden KW. Activation of type-2 chloride channels: a novel therapeutic target for the treatment of chronic constipation. Curr Opin Investig Drugs. 2007;8:66–70.
    1. Okada Y, Shimizu T, Maeno E, Tanabe S, Wang X, Takahashi N. Volume-sensitive chloride channels involved in apoptotic volume decrease and cell death. J Membrane Biol. 2006;209:21–29. doi: 10.1007/s00232-005-0836-6.
    1. Pinheiro da Silva F, Nizet V. Cell death during sepsis: integration of disintegration in the inflammatory response to overwhelming infection. Apoptosis. 2009;14:509–521. doi: 10.1007/s10495-009-0320-3.
    1. Barret KE. Gastrointestinal Physiology. New York: McGraw-Hill; 2006.
    1. Barret KE, Keely SJ. Chloride secretion by the intestinal epithelium: molecular basis and regulatory aspects. Annu Rev Physiol. 2000;62:535–572. doi: 10.1146/annurev.physiol.62.1.535.
    1. Guyton AC, Hall JE. Textbook of Medical Physiology. 11. Philadelphia: Elsevier Sanders; 2006.
    1. Corey HE. In: Critical Care Nephrology. 2. Ronco C, Bellomo R, Kellum JA, editor. Philadelphia: Elsevier Sanders; 2009. Renal acid-base physiology; pp. 587–592.
    1. Sindic A, Chang MH, Mount DB, Romero MF. Renal physiology of SLC26 anion exchangers. Curr Opin Nephrol Hypertens. 2007;16:484–490. doi: 10.1097/MNH.0b013e328011cb4a.
    1. Romero MF. Molecular pathophysiology of SLC4 bicarbonate transporters. Curr Opin Nephrol Hypertens. 2005;14:495–501. doi: 10.1097/01.mnh.0000168333.01831.2c.
    1. Ring T, Frische S, Nielsen S. Clinical review: renal tubular acidosis - a physicochemical approach. Crit Care. 2005;9:573–580. doi: 10.1186/cc3802.
    1. Kellum JA. Determinants of plasma acid-base balance. Crit Care Clin. 2005;21:329–346. doi: 10.1016/j.ccc.2005.01.010.
    1. Wakim KG. 'Normal' 0.9% salt solution is neither 'normal' nor physiological [letter] JAMA. 1970;214:1710. doi: 10.1001/jama.214.9.1710b.
    1. Reid F, Lobo DN, Williams RN, Rowlands BJ, Allison SP. (Ab)normal saline and physiological Hartmann's solution: a randomized double-blind crossover study. Clin Sci. 2003;104:17–24. doi: 10.1042/CS20020202.
    1. Latta T. Malignant cholera. Lancet. 1832;ii:1831–274.
    1. Awad S, Allison SP, Lobo DN. The history of 0.9% saline. Clin Nutr. 2008;27:179–188. doi: 10.1016/j.clnu.2008.01.008.
    1. Stoneham MD, Hill EL. Variability in post-operative fluid and electrolyte prescription. Br J Clin Pract. 1997;51:82–84.
    1. Lobo DN, Dube MG, Neal KR, Simpson JS, Rowlands BJ, Allison SP. Problems with solutions: drowning in the brine of an inadequate knowledge base. Clin Nutr. 2001;20:125–130. doi: 10.1054/clnu.2000.0154.
    1. Kellum JA, Bellomo R, Kramer DJ, Pinsky MR. Etiology of metabolic acidosis during saline resuscitation in endotoxaemia. Shock. 1998;9:364–368. doi: 10.1097/00024382-199805000-00009.
    1. Kellum JA. Fluid resuscitation and hyperchloraemic acidosis in experimental sepsis: improved short-term survival and acid-base balance with Hextend compared with saline. Crit Care Med. 2002;30:300–305. doi: 10.1097/00003246-200202000-00006.
    1. Kellum JA, Song M, Venkataraman R. Effects of hyperchloraemic acidosis on arterial pressure and circulating inflammatory molecules in experimental sepsis. Chest. 2004;125:243–248. doi: 10.1378/chest.125.1.243.
    1. Kellum JA, Song M, Li J. Lactic and hydrochloric acids induce different patterns of inflammatory response in LPS-stimulated RAW 264.7 cells. Am J Physiol Regul Integr Comp Physiol. 2004;286:R686–R692.
    1. Kellum JA, Song M, Almasri E. Hyperchloraemic acidosis increases circulating inflammatory molecules in experimental sepsis. Chest. 2006;130:962–967. doi: 10.1378/chest.130.4.962.
    1. Kellum JA. Metabolic acidosis in patients with sepsis: epiphenomenon or part of the pathophysiology? Crit Care Resusc. 2004;6:197–203.
    1. Pedoto A, Caruso JE, Nandi J. Acidosis stimulates nitric oxide production and lung damage in rats. Am J Respir Crit Care Med. 1999;159:397–402.
    1. Pedoto A, Nandi J, Oler A, Camporesi AM, Hakim TS, Levine RA. Role of nitric oxide in acidosis-induced intestinal injury in anaesthetized rats. J Lab Clin Med. 2001;138:270–276. doi: 10.1067/mlc.2001.118176.
    1. Wilcox CS. Regulation of renal blood flow by plasma chloride. J Clin Invest. 1983;71:726–735. doi: 10.1172/JCI110820.
    1. Schnermann J, Ploth DW, Hermle M. Activation of tubulo-glomerular feedback by chloride transport. Pflugers Arch. 1976;362:229–240. doi: 10.1007/BF00581175.
    1. Eaton D, Pooler J. Vander's Renal Physiology. 7. New York: McGraw-Hill Medical; 2009.
    1. Bullivant EMA, Wilcox CS, Welch WJ. Intrarenal vasoconstriction during hyperchloraemia: role of thromboxane. Am J Physiol. 1989;256:152–157.
    1. Quilley CP, Lin YS, McGiff JC. Chloride anion concentration as a determinant of renal vascular responsiveness to vasoconstrictor agents. Br J Pharmacol. 1993;108:106–110.
    1. Williams EL, Hildebrand KL, McCormick SA, Bedel MJ. The effect of intravenous lactated Ringer's solution versus 0.9% sodium chloride solution on serum osmolality in human volunteers. Anesth Analg. 1999;88:999–1003. doi: 10.1097/00000539-199905000-00006.
    1. Boldt J, Suttner S, Brosch C, Lehmann A, Rohm K, Mengistu A. The influence of a balanced volume replacement concept on inflammation, endothelial activation, and kidney integrity in elderly cardiac surgery patients. Intensive Care Med. 2009;35:462–470. doi: 10.1007/s00134-008-1287-1.
    1. O'Malley CMN, Frumento RJ, Bennett-Guerrero E. Intravenous fluid therapy in renal transplant recipients: results of a U.S. survey. Transplant Proc. 2002;34:3142–3145. doi: 10.1016/S0041-1345(02)03593-5.
    1. O'Malley CMN, Frumento RJ, Hardy MA, Benvenisty AI, Brentjens TE, Mercer JS, Bennett-Guerrero E. A randomized, double-blind comparison of lactated Ringer's solution and 0.9% NaCl during renal transplantation. Anesth Analg. 2005;100:1518–1524. doi: 10.1213/01.ANE.0000150939.28904.81.
    1. Mythen MG, Hamilton MA. Hyperchloremic metabolic acidosis: is it clinically relevant? Transfus Altern Transfus Med. 2001;4:15–19. doi: 10.1111/j.1778-428X.2001.tb00040.x.
    1. Tournadre JP, Allaouchiche B, Malbert CH, Chassard D. Metabolic acidosis and respiratory acidosis impair gastro-pyloric motility in anesthetized pigs. Anesth Analg. 2000;90:74–79. doi: 10.1097/00000539-200001000-00018.
    1. Traverso LW, Lee WP, Langford MJ. Fluid resuscitation after an otherwise fatal hemorrhage: I. Crystalloid solutions. J Trauma. 1986;26:168–175. doi: 10.1097/00005373-198602000-00014.
    1. Healey MA, Davis R, Liu FC, Loomis WH, Hoyt DB. Lactated Ringer's is superior to normal saline in a model of massive hemorrhage and resuscitation. J Trauma. 1998;45:894–899. doi: 10.1097/00005373-199811000-00010.
    1. Ho AM-H, Karmakar KM, Contardi LH, Ng SW, Hewson JR. Excessive use of normal saline in managing traumatized patients in shock: a preventable contributor to acidosis. Trauma. 2001;51:173–177. doi: 10.1097/00005373-200107000-00033.
    1. Gan TJ, Bennett-Guerrero E, Phillips-Bute B, Wakeling H, Moskowitz DM, Olufolabi Y, Konstadt SN, Bradford C, Glass PSA, Machin SJ, Mythen MG. Hextend® Study Group. Hextend®, a physiologically balanced plasma expander for large volume use in major surgery: a randomized phase III clinical trial. Anesth Analg. 1999;88:992–998. doi: 10.1097/00000539-199905000-00005.
    1. Martin G, Bennett-Guererro E, Wakeling H, Mythen MG, El-Moalem H, Robertson K, Kucmeroski D, Gan TJ. A prospective, randomized comparison of thromboelastographic coagulation profile in patients receiving lactated Ringer's solution, 6% hetastarch in a balanced-saline vehicle, or 6% hetastarch in saline during major surgery. J Cardiothorac Vasc Anesth. 2002;16:441–446. doi: 10.1053/jcan.2002.125146.
    1. Roche AM, James MFM, Grocott MPW, Mythen MG. Coagulation effects of in vitro serial haemodilution with a balanced electrolyte hetastarch solution compared with a saline-based hetastarch solution and lactated Ringer's solution. Anaesthesia. 2002;57:950–955. doi: 10.1046/j.1365-2044.2002.02707.x.
    1. Roche AM, James MFM, Bennett-Guerrero E, Mythen MG. A head-to-head comparison of the in vitro coagulation effects of saline-based and balanced electrolyte crystalloid and colloid intravenous fluids. Anesth Analg. 2006;102:1274–1279. doi: 10.1213/01.ane.0000197694.48429.94.
    1. Boldt J, Wolf M, Mengistu A. A new plasma-adapted hydroxyethylstarch preparation: in vitro coagulation studies using thromboelastography and whole blood aggregometry. Anesth Analg. 2007;104:425–430. doi: 10.1213/01.ane.0000253484.19070.87.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit