Hyperchloremia is an
electrolyte disturbance
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 ...
in which there is an elevated level of
chloride
The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride sa ...
ions in the
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
.
The normal serum range for chloride is 96 to 106
mEq/L
An equivalent (symbol: officially equiv; unofficially but often Eq) is the amount of a substance that reacts with (or is ''equivalent'' to) an arbitrary amount (typically one mole) of another substance in a given chemical reaction. It is an arc ...
,
therefore chloride levels at or above 110 mEq/L usually indicate
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
dysfunction as it is a regulator of chloride concentration.
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
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...
,
vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteri ...
, increased sodium chloride intake,
renal dysfunction
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
,
diuretic
A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics i ...
use, and
diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
. 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
In inorganic chemistry, bicarbonate (IUPAC-recommended nomenclature: hydrogencarbonate) is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula .
Bicarbonate serves a crucial biochem ...
levels, as well as an increase in blood chloride levels.
Instead those with hyperchloremic metabolic acidosis are usually predisposed to hyperchloremia.
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
Saline (also known as saline solution) 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 i ...
. Previously, animal models with elevated chloride have displayed more inflammation markers, changes in
blood pressure, increased
renal
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...
vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vess ...
, 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
Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both.
Causes of AKI are c ...
in severely ill patients that may frequent the hospital or have prolonged visits. There are other studies that have found no relationship.
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:
*Dehydration - due to diarrhea, vomiting, sweating
*Hypertension - due to increased sodium chloride intake
*Cardiovascular dysfunction - due to increased sodium chloride intake
*Edema - due to influx in sodium in the body
*Weakness - due to loss of fluids
*Thirst - due to loss of fluids
*
Kussmaul breathing
Kussmaul breathing is a deep and labored breathing pattern often associated with severe metabolic acidosis, particularly diabetic ketoacidosis (DKA) but also kidney failure. It is a form of hyperventilation, which is any breathing pattern that red ...
- due to high ion concentrations, loss of fluids, or kidney failure
*
High blood sugar
Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...
- due to diabetes
*Hyperchloremic metabolic acidosis - due to severe diarrhea and/or kidney failure
*
Respiratory alkalosis
Respiratory alkalosis is a medical condition in which increased respiration elevates the blood pH beyond the normal range (7.35–7.45) with a concurrent reduction in arterial levels of carbon dioxide. This condition is one of the four primary dis ...
- due to renal dysfunction
*
*
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
In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
and dry
mucous membrane
A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It i ...
.
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.
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.
Mechanism
The
nephron
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 ...
s in the
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
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
In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 60% (range 45 to 75%) of total body weight; women and the obese typically have a lower ...
or absorbed into the lumen. All along the nephrons are
blood capillaries
A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the bod ...
waiting to reabsorb ions from the interstitial fluid to circulate in the body.
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
The proximal tubule is the segment of the nephron in kidneys which begins from the renal pole of the Bowman's capsule to the beginning of loop of Henle. It can be further classified into the proximal convoluted tubule (PCT) and the proximal strai ...
and nearly 60% of chloride is filtered here.
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.
In the proximal tubule chloride reabsorption occurs in two parts. In the 1st phase, organic solutes (such as
phosphate
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid .
The phosphate or orthophosphate ion is derived from phosph ...
s,
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
s,
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
and
anions
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...
), sodium ions, and
hydronium
In chemistry, hydronium (hydroxonium in traditional British English) is the common name for the aqueous cation , the type of oxonium ion produced by protonation of water. It is often viewed as the positive ion present when an Arrhenius acid i ...
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.
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 channel
Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration ''in vivo'' is much higher than other anions. Several ...
s. 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
Passive transport is a type of membrane transport that does not require energy to move substances across cell membranes. Instead of using cellular energy, like active transport, passive transport relies on the second law of thermodynamics to dri ...
of chloride in and out the tubule.
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.
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.
Treatment
As with most types of electrolyte imbalance, the treatment of high blood chloride levels is based on correcting the underlying cause.
*If the patient is dehydrated, therapy consists of establishing and maintaining adequate hydration
such as drinking 2-3
quart
The quart (symbol: qt) is an English unit of volume equal to a quarter gallon. Three kinds of quarts are currently used: the liquid quart and dry quart of the US customary system and the of the British imperial system. All are roughly equ ...
s of water daily. Also, to alleviate symptoms of dehydration like diarrhea or vomiting, it is suggested to take medication.
*If the condition is caused or exacerbated by medications or treatments, these may be altered or discontinued, if deemed prudent.
*If there is underlying kidney disease (which is likely if there are other electrolyte disturbances), then the patient will be referred to a
nephrologist
Nephrology (from Greek'' nephros'' "kidney", combined with the suffix ''-logy'', "the study of") is a specialty of adult internal medicine and pediatric medicine that concerns the study of the kidneys, specifically normal kidney function ( ...
for further care.
*If there is an underlying dysfunction of the endocrine or hormone system, the patient will likely be referred to an
endocrinologist
Endocrinology (from ''endocrine'' + '' -ology'') is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions known as hormones. It is also concerned with the integration of developmental events ...
for further assessment.
*If the electrolyte imbalance is due to influx of sodium chloride in the body, then it has been suggested to make dietary changes or reduce the rate of administering intravenous fluids.
Recent research
In patients with
sepsis
Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
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.
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
In statistics, a confounder (also confounding variable, confounding factor, extraneous determinant or lurking variable) is a variable that influences both the dependent variable and independent variable, causing a spurious association. Con ...
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
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. 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. 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.
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.
References
External links
{{Electrolyte abnormalities
Electrolyte disturbances