Hyperchloremia

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Hyperchloremia
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Chlorine
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Hyperchloremia is an electrolyte disturbance in which there is an elevated level of chloride ions in the blood. [1] The normal serum range for chloride is 96 to 106 mEq/L, [2] therefore chloride levels at or above 110 mEq/L usually indicate kidney dysfunction as it is a regulator of chloride concentration. [3] As of now there are no specific symptoms of hyperchloremia; however, it can be influenced by multiple abnormalities that cause a loss of electrolyte-free fluid, loss of hypotonic fluid, or increased administration of sodium chloride. These abnormalities are caused by diarrhea, vomiting, increased sodium chloride intake, renal dysfunction, diuretic use, and diabetes. Hyperchloremia should not be mistaken for hyperchloremic metabolic acidosis as hyperchloremic metabolic acidosis is characterized by two major changes: a decrease in blood pH and bicarbonate levels, as well as an increase in blood chloride levels. [3] Instead those with hyperchloremic metabolic acidosis are usually predisposed to hyperchloremia.

Contents

Hyperchloremia prevalence in hospital settings has been researched in the medical field since one of the major sources of treatment at hospitals is administering saline solution. Previously, animal models with elevated chloride have displayed more inflammation markers, changes in blood pressure, increased renal vasoconstriction, and less renal blood flow as well at glomerulus filtration, all of which are prompting researchers to investigate if these changes or others may exist in patients. Some studies have reported a possible relationship between increased chloride levels and death or acute kidney injury in severely ill patients that may frequent the hospital or have prolonged visits. There are other studies that have found no relationship. [4]

Symptoms

Hyperchloremia does not have many noticeable symptoms and can only be confirmed with testing, yet, the causes of hyperchloremia do have symptoms.

Symptoms of the above stated abnormalities may include: [5]

Causes

There are many scenarios which may results in hyperchloremia. The first instance is when there is a loss of electrolyte-free fluid. This simply means that the body is losing increased amounts of fluids that do not contain electrolytes, like chloride, resulting in high concentration of these ions in the body. This loss of fluids can be due to sweating (due to exercise or fever), skin burns, lack of adequate water intake, hyper-metabolic state, and diabetes insipidus. Losing fluids can lead to feelings of dehydration and dry mucous membrane. [4] [5]

The second scenario that may lead to hyperchloremia is known as loss of hypotonic fluid which can be a direct result of loss of electrolyte fluid. Normally, water in the body is moving from an area of low ion concentration to an area of high ion concentration. In this case, the water is being excreted in the urine, therefore, less water is available to dilute these areas of high ion concentration. This can be due to diuretic use, diarrhea, vomiting, burns, kidney disease, kidney failure, and renal tubular acidosis . This may also lead to feeling of dehydration. [4] [5]

The third scenario that may lead to hyperchloremia is an increase in sodium chloride intake. This can be due to dietary intake or intravenous fluid administration in hospital settings. This can lead to the body experiencing hypertension, edema, and cardiovascular dysfunction. [4] [5]

Mechanism

The nephrons in the kidney are responsible for regulating the level of chloride in the blood. The general mechanism is that as filtrate fluid passes through the nephrons varying concentrations of ions will be secreted into the interstitial fluid or absorbed into the lumen. All along the nephrons are blood capillaries waiting to reabsorb ions from the interstitial fluid to circulate in the body. [6] The amount of chloride to be released in the urine is due to the receptors lining the nephrons and the glomerulus filtration.

Normally, chloride reabsorption begins in the proximal tubule and nearly 60% of chloride is filtered here. [7] In a person with hyperchloremia, the absorption of chloride into the interstitial fluid and subsequently into the blood capillaries is increased. This means the concentration of chloride in the filtrate is decreased, therefore, a decreased amount of chloride is being excreted as waste in the urine. [6] In the proximal tubule chloride reabsorption occurs in two parts. In the 1st phase, organic solutes (such as phosphates, amino acids, glucose and anions), sodium ions, and hydronium ions are reabsorbed from the filtrate fluid into the interstitial fluid. This is an important step because this creates the concentration gradient in which chloride concentration in the lumen will increase in comparison to the chloride concentration in the interstitial fluid. In phase 2, chloride will diffuse along the concentration gradient, which means chloride ions will travel from areas of high concentration to areas of low concentration. [5]

One suggested mechanism leading to hyperchloremia, there is a decrease in chloride transporter proteins along the nephron. These proteins may include sodium-potassium-2 chloride co-transporter, chloride anion exchangers, and chloride channels. Another suggested mechanism is a depletion in concentration gradient as a result of the reduced activity in these transporters. Such concentration gradient depletion would allow for the passive diffusion of chloride in and out the tubule. [7]

Diagnosis

Elevated levels of chloride in the blood can be tested simply by requesting a serum chloride test. A doctor would request this test if there are signs their patient is experiencing an imbalance in acid-base levels for a prolonged period of time. [2] [8] For the test to occur a healthcare provider must draw a sample of blood from the patient. The sample will then be sent to a laboratory and results will be provided to the patient's physician. As mentioned earlier a normal serum chloride range is from 96 to 106 mEq/L, and hyperchloremic patients will have levels above this range. [2]

Treatment

As with most types of electrolyte imbalance, the treatment of high blood chloride levels is based on correcting the underlying cause.

Recent research

In patients with sepsis or septic shock they are more susceptible to experience acute kidney injury (AKI) and the factors that may contribute to AKI are still being investigated. In a study conducted by Suetrong et al., (2016) using patients admitted to St. Paul Hospital in Vancouver with sepsis or septic shock had their body concentration of chloride checked over the course of 48 hours to determine if there is a relation between hyperchloremia and AKI. This is an important relationship to study because many times a form of therapy to treat sepsis and septic shock is to administer saline solution, which is a solution containing sodium chloride. Saline has a much higher concentration of chloride than blood. In this study they defined hyperchloremia as concentration of chloride greater than 110 mmol/L. This research demonstrated that hyperchloremia will influence a patient developing AKI. In fact, even patients that had a conservative increase in serum chloride saw some association with developing AKI. This research study suggest that there still needs to be more investigation in the risk of using saline as a form of therapy and the risk of experiencing AKI. [10]

In a separate study investigating the relation of critically ill patients and hyperchloremia, researchers found that there seems to be an independent association between ill patients with hyperchloremia and mortality. This study was conducted with septic patients admitted to ICUs for 72 hours. Chloride levels were assessed at baseline and 72 hours, and confounding variables were accounted for. This study is important because this continues to suggest there is increased risk associated with elevated chloride levels in vulnerable populations. Their article also states there needs to be avoidance of using solutions with chloride in specific patient subgroups [11]

Several trials have been done comparing balanced fluid (chloride restricted) solution with saline (chloride liberal) with the hypothesis that it may reduce the risk of AKI and mortality. Initial randomized trials in septic shock comparing Plasma-Lyte and 0.9% saline (SPLIT and SALT trials) did not show any risk reduction in AKI. [12] [13] However, the later trials with larger sample size in critically and non critically ill adults (SMART and SALT-ED trials) showed reduction in major adverse kidney events. [14] [15] Extrapolating from the findings of septic shock, a recent trial comparing plasmalyte with 0.9% saline in DKA also did not show any significant difference in AKI. Hence, the causal link between hyperchloremia and AKI is yet to be conclusively established. [16]

As studies continue, it is important to include a large patient sample size, a diverse patient population, and a diverse range of hospitals involved in these studies. [4]

Related Research Articles

<span class="mw-page-title-main">Nephron</span> Microscopic structural and functional unit of the kidney

The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure called Bowman's capsule. The renal tubule extends from the capsule. The capsule and tubule are connected and are composed of epithelial cells with a lumen. A healthy adult has 1 to 1.5 million nephrons in each kidney. Blood is filtered as it passes through three layers: the endothelial cells of the capillary wall, its basement membrane, and between the foot processes of the podocytes of the lining of the capsule. The tubule has adjacent peritubular capillaries that run between the descending and ascending portions of the tubule. As the fluid from the capsule flows down into the tubule, it is processed by the epithelial cells lining the tubule: water is reabsorbed and substances are exchanged ; first with the interstitial fluid outside the tubules, and then into the plasma in the adjacent peritubular capillaries through the endothelial cells lining that capillary. This process regulates the volume of body fluid as well as levels of many body substances. At the end of the tubule, the remaining fluid—urine—exits: it is composed of water, metabolic waste, and toxins.

<span class="mw-page-title-main">Fluid replacement</span>

Fluid replacement or fluid resuscitation is the medical practice of replenishing bodily fluid lost through sweating, bleeding, fluid shifts or other pathologic processes. Fluids can be replaced with oral rehydration therapy (drinking), intravenous therapy, rectally such as with a Murphy drip, or by hypodermoclysis, the direct injection of fluid into the subcutaneous tissue. Fluids administered by the oral and hypodermic routes are absorbed more slowly than those given intravenously.

<span class="mw-page-title-main">Renal physiology</span> Study of the physiology of the kidney

Renal physiology is the study of the physiology of the kidney. This encompasses all functions of the kidney, including maintenance of acid-base balance; regulation of fluid balance; regulation of sodium, potassium, and other electrolytes; clearance of toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pressure; production of various hormones, such as erythropoietin; and activation of vitamin D.

<span class="mw-page-title-main">Hyperkalemia</span> Medical condition with excess potassium

Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5 mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasionally when severe it can cause palpitations, muscle pain, muscle weakness, or numbness. Hyperkalemia can cause an abnormal heart rhythm which can result in cardiac arrest and death.

<span class="mw-page-title-main">Electrolyte imbalance</span> Medical condition

Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, fluid balance, oxygen delivery, acid–base balance and much more. Electrolyte imbalances can develop by consuming too little or too much electrolyte as well as excreting too little or too much electrolyte. Examples of electrolytes include calcium, chloride, magnesium, phosphate, potassium, and sodium.

<span class="mw-page-title-main">Hypovolemic shock</span> Medical condition

Hypovolemic shock is a form of shock caused by severe hypovolemia. It could be the result of severe dehydration through a variety of mechanisms or blood loss. Hypovolemic shock is a medical emergency; if left untreated, the insufficient blood flow can cause damage to organs, leading to multiple organ failure.

<span class="mw-page-title-main">Loop diuretic</span> Diuretics that act at the ascending limb of the loop of Henle in the kidney

Loop diuretics are diuretics that act on the Na-K-Cl cotransporter along the thick ascending limb of the loop of Henle in nephrons of the kidneys. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or chronic kidney disease. While thiazide diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function.

<span class="mw-page-title-main">Metabolic acidosis</span> Medical condition

Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys to excrete excess acids. Metabolic acidosis can lead to acidemia, which is defined as arterial blood pH that is lower than 7.35. Acidemia and acidosis are not mutually exclusive – pH and hydrogen ion concentrations also depend on the coexistence of other acid-base disorders; therefore, pH levels in people with metabolic acidosis can range from low to high.

<span class="mw-page-title-main">Saline (medicine)</span> Saline water for medical purposes

Saline is a mixture of sodium chloride (salt) and water. It has a number of uses in medicine including cleaning wounds, removal and storage of contact lenses, and help with dry eyes. By injection into a vein, it is used to treat dehydration such as that from gastroenteritis and diabetic ketoacidosis. Large amounts may result in fluid overload, swelling, acidosis, and high blood sodium. In those with long-standing low blood sodium, excessive use may result in osmotic demyelination syndrome.

<span class="mw-page-title-main">Ringer's lactate solution</span> Fluid used for resuscitation after blood loss

Ringer's lactate solution (RL), also known as sodium lactate solution,Lactated Ringer's, and Hartmann's solution, is a mixture of sodium chloride, sodium lactate, potassium chloride, and calcium chloride in water. It is used for replacing fluids and electrolytes in those who have low blood volume or low blood pressure. It may also be used to treat metabolic acidosis and to wash the eye following a chemical burn. It is given by intravenous infusion or applied to the affected area.

The anion gap is a value calculated from the results of multiple individual medical lab tests. It may be reported with the results of an electrolyte panel, which is often performed as part of a comprehensive metabolic panel.

<span class="mw-page-title-main">Hypoaldosteronism</span> Medical condition

Hypoaldosteronism is an endocrinological disorder characterized by decreased levels of the hormone aldosterone. Similarly, isolated hypoaldosteronism is the condition of having lowered aldosterone without corresponding changes in cortisol.

<span class="mw-page-title-main">Metabolic alkalosis</span> Medical condition

Metabolic alkalosis is a metabolic condition in which the pH of tissue is elevated beyond the normal range (7.35–7.45). This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations. The condition typically cannot last long if the kidneys are functioning properly.

Hyperchloremic acidosis is a form of metabolic acidosis associated with a normal anion gap, a decrease in plasma bicarbonate concentration, and an increase in plasma chloride concentration. Although plasma anion gap is normal, this condition is often associated with an increased urine anion gap, due to the kidney's inability to secrete ammonia.

<span class="mw-page-title-main">Renal tubular acidosis</span> Medical condition

Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. In renal physiology, when blood is filtered by the kidney, the filtrate passes through the tubules of the nephron, allowing for exchange of salts, acid equivalents, and other solutes before it drains into the bladder as urine. The metabolic acidosis that results from RTA may be caused either by insufficient secretion of hydrogen ions into the latter portions of the nephron or by failure to reabsorb sufficient bicarbonate ions from the filtrate in the early portion of the nephron. Although a metabolic acidosis also occurs in those with chronic kidney disease, the term RTA is reserved for individuals with poor urinary acidification in otherwise well-functioning kidneys. Several different types of RTA exist, which all have different syndromes and different causes. RTA is usually an incidental finding based on routine blood draws that show abnormal results. Clinically, patients may present with vague symptoms such as dehydration, mental status changes, or delayed growth in adolescents.

<span class="mw-page-title-main">Metolazone</span> Chemical compound

Metolazone is a thiazide-like diuretic marketed under the brand names Zytanix, Metoz, Zaroxolyn, and Mykrox. It is primarily used to treat congestive heart failure and high blood pressure. Metolazone indirectly decreases the amount of water reabsorbed into the bloodstream by the kidney, so that blood volume decreases and urine volume increases. This lowers blood pressure and prevents excess fluid accumulation in heart failure. Metolazone is sometimes used together with loop diuretics such as furosemide or bumetanide, but these highly effective combinations can lead to dehydration and electrolyte abnormalities.

<span class="mw-page-title-main">Bartter syndrome</span> Medical condition

Bartter syndrome (BS) is a rare inherited disease characterised by a defect in the thick ascending limb of the loop of Henle, which results in low potassium levels (hypokalemia), increased blood pH (alkalosis), and normal to low blood pressure. There are two types of Bartter syndrome: neonatal and classic. A closely associated disorder, Gitelman syndrome, is milder than both subtypes of Bartter syndrome.

Normal anion gap acidosis is an acidosis that is not accompanied by an abnormally increased anion gap.

A volume expander is a type of intravenous therapy that has the function of providing volume for the circulatory system. It may be used for fluid replacement or during surgery to prevent nausea and vomiting after surgery.

The urine anion gap is calculated using measured ions found in the urine. It is used to aid in the differential diagnosis of metabolic acidosis.

References

  1. 1 2 3 4 5 Cambier C, Detry B, Beerens D, et al. (October 1998). "Effects of hyperchloremia on blood oxygen binding in healthy calves". J. Appl. Physiol. 85 (4): 1267–72. doi:10.1152/jappl.1998.85.4.1267. PMID   9760315. S2CID   1778217.
  2. 1 2 3 "Chloride test - blood: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2017-12-12.
  3. 1 2 "Hyperchloremic metabolic acidosis". dynamed.com. Archived from the original on 2019-02-13. Retrieved 2017-12-12.
  4. 1 2 3 4 5 6 Bandak, Ghassan; Kashani, Kianoush B. (2017-11-01). "Chloride in intensive care units: a key electrolyte". F1000Research. 6: 1930. doi: 10.12688/f1000research.11401.1 . PMC   5668919 . PMID   29123653.
  5. 1 2 3 4 5 Morrison, Gail (1990). Walker, H. Kenneth; Hall, W. Dallas; Hurst, J. Willis (eds.). Clinical Methods: The History, Physical, and Laboratory Examinations (3rd ed.). Boston: Butterworths. ISBN   978-0409900774. PMID   21250151.
  6. 1 2 Hall, J, Guyton, A (2016). Textbook of Medical Physiology. Elsevier. ISBN   978-1455770052.{{cite book}}: CS1 maint: multiple names: authors list (link)
  7. 1 2 Nagami, Glenn T. (2016-07-01). "Hyperchloremia – Why and how". Nefrología (English Edition). 36 (4): 347–353. doi: 10.1016/j.nefroe.2016.06.006 . ISSN   2013-2514. PMID   27267918.
  8. ↑ Cancer, Cleveland Clinic. "Hyperchloremia (High Chloride) - Managing Side Effects - Chemocare". chemocare.com. Archived from the original on 2020-03-27. Retrieved 2017-12-12.
  9. 1 2 "Hyperchloremia (high chloride): Symptoms, causes, and treatments". Medical News Today. Retrieved 2017-12-13.
  10. ↑ Suetrong, Bandarn; Pisitsak, Chawika; Boyd, John H.; Russell, James A.; Walley, Keith R. (2016-10-06). "Hyperchloremia and moderate increase in serum chloride are associated with acute kidney injury in severe sepsis and septic shock patients". Critical Care. 20 (1): 315. doi: 10.1186/s13054-016-1499-7 . ISSN   1364-8535. PMC   5053142 . PMID   27716310.
  11. ↑ Neyra, Javier A.; Canepa-Escaro, Fabrizio; Li, Xilong; Manllo, John; Adams-Huet, Beverley; Yee, Jerry; Yessayan, Lenar (September 2015). "Association of Hyperchloremia with Hospital Mortality in Critically Ill Septic Patients". Critical Care Medicine. 43 (9): 1938–1944. doi:10.1097/CCM.0000000000001161. ISSN   0090-3493. PMC   4537691 . PMID   26154934.
  12. ↑ Young, Paul; Bailey, Michael; Beasley, Richard; Henderson, Seton; Mackle, Diane; McArthur, Colin; McGuinness, Shay; Mehrtens, Jan; Myburgh, John; Psirides, Alex; Reddy, Sumeet; Bellomo, Rinaldo (2015-10-27). "Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial". JAMA. 314 (16): 1701–10. doi: 10.1001/jama.2015.12334 . ISSN   0098-7484. PMID   26444692.
  13. ↑ Semler, Matthew W.; Wanderer, Jonathan P.; Ehrenfeld, Jesse M.; Stollings, Joanna L.; Self, Wesley H.; Siew, Edward D.; Wang, Li; Byrne, Daniel W.; Shaw, Andrew D.; Bernard, Gordon R.; Rice, Todd W.; Bernard, Gordon R.; Semler, Matthew W.; Noto, Michael J.; Rice, Todd W.; Byrne, Daniel W.; Domenico, Henry J.; Wang, Li; Wanderer, Jonathan P.; Ehrenfeld, Jesse M.; Shaw, Andrew D.; Hernandez, Antonio; Kumar, Avinash B.; Self, Wesley H.; Siew, Edward D.; Dunlap, Debra F.; Stollings, Joanna L.; Sullivan, Mark; Knostman, Molly; Mulherin, David P.; Hargrove, Fred R.; Janz, David R.; Strawbridge, Seth (2017-05-15). "Balanced Crystalloids versus Saline in the Intensive Care Unit. The SALT Randomized Trial". American Journal of Respiratory and Critical Care Medicine. 195 (10): 1362–1372. doi:10.1164/rccm.201607-1345OC. ISSN   0003-0805. PMC   5443900 . PMID   27749094.
  14. ↑ Semler, Matthew W.; Self, Wesley H.; Wanderer, Jonathan P.; Ehrenfeld, Jesse M.; Wang, Li; Byrne, Daniel W.; Stollings, Joanna L.; Kumar, Avinash B.; Hughes, Christopher G.; Hernandez, Antonio; Guillamondegui, Oscar D.; May, Addison K.; Weavind, Liza; Casey, Jonathan D.; Siew, Edward D.; Shaw, Andrew D.; Bernard, Gordon R.; Rice, Todd W. (March 2018). "Balanced Crystalloids versus Saline in Critically Ill Adults". New England Journal of Medicine. 378 (9): 829–839. doi:10.1056/NEJMoa1711584. ISSN   0028-4793. PMC   5846085 . PMID   29485925.
  15. ↑ Self, Wesley H.; Semler, Matthew W.; Wanderer, Jonathan P.; Wang, Li; Byrne, Daniel W.; Collins, Sean P.; Slovis, Corey M.; Lindsell, Christopher J.; Ehrenfeld, Jesse M.; Siew, Edward D.; Shaw, Andrew D.; Bernard, Gordon R.; Rice, Todd W. (March 2018). "Balanced Crystalloids versus Saline in Noncritically Ill Adults". New England Journal of Medicine. 378 (9): 819–828. doi:10.1056/NEJMoa1711586. ISSN   0028-4793. PMC   5846618 . PMID   29485926.
  16. ↑ Williams, Vijai; Jayashree, Muralidharan; Nallasamy, Karthi; Dayal, Devi; Rawat, Amit (December 2020). "0.9% saline versus Plasma-Lyte as initial fluid in children with diabetic ketoacidosis (SPinK trial): a double-blind randomized controlled trial". Critical Care. 24 (1): 1. doi: 10.1186/s13054-019-2683-3 . ISSN   1364-8535. PMC   6939333 . PMID   31898531.
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