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High Chloride Levels (Hyperchloremia) Symptoms & Causes

Written by Carlos Tello, PhD (Molecular Biology) | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Puya Yazdi
Medically reviewed by
Puya Yazdi, MD | Written by Carlos Tello, PhD (Molecular Biology) | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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Discussing blood test results with a doctor

Chloride plays an important role in acid and electrolyte balance, kidney and muscle function, and the transport of minerals, water, and gases. Both high and low blood chloride levels can cause health issues. Keep reading to learn more about high chloride levels and the symptoms and disorders caused by it.

Disclaimer: The symptoms and conditions we discuss here are commonly associated with high chloride, but high chloride alone is not enough for a diagnosis. Work with your doctor to discover what underlying condition might be causing your high chloride levels to develop an appropriate plan to improve your health.

Symptoms of High Chloride (Hyperchloremia)

High chloride levels (>106-110 mEq/L) are known as hyperchloremia.

Long-term or severe hyperchloremia can have the following symptoms from dehydration and metabolic acidosis (low blood pH) [1, 2]:

  • Diarrhea
  • Vomiting
  • Headache
  • Apathy
  • Thirst
  • Muscle cramps
  • Irregular heart rate
  • Confusion
  • Numbness or tingling
  • Seizures
  • Breathing problems
  • Fever
  • Sweating
Symptoms of high chloride levels depend on the underlying cause, such as dehydration or metabolic acidosis.

Causes of High Chloride Levels

Overview

High blood chloride can be caused by:

  • Dehydration [3, 4]
  • Conditions that can cause fluid loss, such as fever or diarrhea [4, 5]
  • Too much stress, which causes high cortisol levels (adrenal hyperfunction) [6]
  • Parathyroid hyperfunction (hyperparathyroidism) [7, 4, 8]
  • Kidney disease [3, 9]
  • Metabolic acidosis [3, 4]
  • Hyperventilation causing respiratory alkalosis [3, 4]
  • Diabetes insipidus (a rare condition where the body produces a large amount of urine and one often feels thirsty) [4]
  • Bromide intoxication [4]
  • Drugs such as aspirin [10]

1) Dehydration

Dehydration increases the concentration of chloride in the body by decreasing the amount of water. In these conditions, the kidneys reduce urine production to preserve more water [11].

Dehydration can be caused by [3]:

  • Insufficient water intake
  • Vomiting
  • Diarrhea
  • High fever
  • Heat exposure
  • Intense exercise
  • Alcohol abuse
  • Some medications (e.g., diuretics)
  • Production of large amounts of diluted urine (diabetes insipidus)
  • Increased urine production as a result of high salt intake

2) Excessive Salt Intake

Excessive salt intake (salty food, infusion of 0.9% salt solution during patient resuscitation, or unintentionally swallowing salty water) exceeds the capacity of the kidneys to excrete sodium and chloride, and increases water loss from urination and diarrhea. This leads to a buildup of both electrolytes [12, 3, 13].

3) Metabolic Acidosis

Metabolic acidosis (low blood pH) occurs when the body produces excessive acids or insufficient bicarbonate. This loss of bicarbonate increases the concentration of chloride to maintain negative charges in the blood [14, 15].

Alternatively, some forms of diarrhea cause the excretion of bicarbonate, which increases chloride retention [16].

Chloride buildup linked to metabolic acidosis also occurs in a condition in which the kidneys fail to absorb bicarbonate (proximal kidney tubular acidosis) or in patients suffering from chronic kidney failure [17, 18].

Blockers of the enzyme that transforms carbon dioxide into bicarbonate (carbonic anhydrase II) also promote chloride buildup [19].

Excessive exposure to certain organic acids (e.g., toluene) can also cause high chloride [20].

4) Electrolyte Imbalances

Positive and negative charges in the blood must be balanced to remain electrically neutral. Conditions promoting the increased buildup of positive electrolytes such as sodium and potassium in the blood will lead to the excessive accumulation of chloride [21].

5) Genetic Disorders

The following genetic conditions are associated with abnormal chloride levels.

Gordon’s Syndrome

Pseudohypoaldosteronism type II (PHAII), also known as Gordon’s syndrome, is a rare hereditary disease characterized by high blood chloride levels [22].

In the kidneys, the proteins WNK1 and WNK4 activate the electrolyte transporters Na+/Cl- cotransporter (NCC) and Na+/K+/2Cl- cotransporters 1 and 2 (NKCC1 and NKCC2), thus causing the increased intake of sodium, chloride, and potassium. Additionally, the proteins KLHL3 and CUL3 form a complex that binds to WNK4 and breaks it down, thus decreasing the absorption of these electrolytes. Mutations in all these proteins can cause Gordon’s syndrome [23, 24, 25, 26].

Consequences of High Chloride Levels

1) Kidney Function

Several studies found a link between high blood chloride levels and increased incidence of kidney injury:

  • A meta-analysis of 21 studies and over 6,000 critically ill people [27]
  • Three observational studies and a clinical trial on over 3,500 critically ill people [28, 9, 29, 30]
  • Two observational studies and a clinical trial on over 32,000 people undergoing surgery [31, 32, 33]
  • A case series on 79 children with diabetic ketoacidosis [34]
  • An observational study on over 200 people with septic shock [35]
  • An observational study on over 1200 people with bleeding in the membrane area of the brain (subarachnoid space) [36]

However, this relationship was not seen in other studies:

  • A retrospective analysis of 95 people with septic shock [37]
  • A retrospective analysis of almost 300 people undergoing heart surgery [38]
  • Two observational studies on almost 1,500 people undergoing surgery [39, 40]
  • An observational study and a clinical trial on over 3,000 critically ill people [41, 42]

In an observational study on over 200 patients who underwent kidney transplantation, no association could be found between high blood chloride levels in the donor and the incidence of acute kidney injury in the recipient [43].

Infusion of 0.9% salt solution reduced blood flow in the kidneys as a result of high blood chloride levels in a clinical trial on 12 healthy volunteers [44].

Several studies suggested a link between high chloride levels and kidney disease complications, but more research is needed.

2) Death Rate

A relationship between high blood chloride levels and increased death rate of critically ill patients has been demonstrated in these studies:

  • An observational study on almost 2,000 people with septic shock [45]
  • Three observational studies on over 110,000 adults with systemic inflammatory syndrome and almost 900 children with septic shock [46, 47, 48]
  • Two observational studies on almost 55,000 people undergoing surgery [31, 49]
  • Three observational studies on over 300 critically ill adults and children [50, 51, 52]

However, this correlation was not seen in these studies:

  • A meta-analysis of 21 studies and over 6,000 critically ill people [27]
  • A clinical trial on over 2,000 people admitted to the intensive care unit [42]
  • An observational study and a clinical trial on over 1,000 critically ill people [30, 28]
  • A clinical trial on over 400 people with septic shock [53]
The link between high chloride levels and death rates is still unclear. The evidence so far has been mixed.

3) Blood Circulation

In 2 clinical trials on over 200 people undergoing major surgery, those infused with 0.9% salt required higher volumes of a neurotransmitter (catecholamine) to increase their blood pressure and support circulation than those infused with a balanced solution [33, 54].

In a trial on 66 people undergoing aortic reconstruction surgery, the infusion with a balanced solution (Ringer’s lactate) instead of 0.9% salt reduced blood loss during the operation [55].

4) Immune System

Infusion with a balanced solution induced higher circulating levels of cytokines than with 0.9% salt solution in a clinical trial on 40 people undergoing surgery [56].

High blood chloride concentrations increased the circulating cytokine levels in a study in rats with septic shock but failed to do so in a similar experiment [57, 58].

In two cell studies, exposure to a chloride-concentrated solution reduced the activation and attachment to the inner blood vessel lining of white blood cells, suggesting that infusion with high-chloride fluids reduces the risk of septic shock [59, 60].

Small studies suggest that people who receive high-chloride infusions may experience high blood pressure and raised cytokines, but this hasn’t been verified.

5) In-Hospital Complications

In a meta-analysis of 21 studies involving over 6,000 critically ill people, infusion with high-chloride fluids was associated with the requirement for longer mechanical ventilation times [27].

In two observational studies on almost 32,000 people undergoing surgery and over 3,000 with systemic inflammatory syndrome, infusion with 0.9% salt increased the incidence of infections after the operation [31, 47].

Infusion with 0.9% salt caused increased readmission rates when compared to a balanced solution in an observational study on over 3,000 people with systemic inflammatory syndrome [47].

High blood chloride levels caused by infusion with 0.9% salt increased the length of hospital stay in two observational studies on over 3,000 people with systemic inflammatory syndrome and over 22,000 undergoing surgery [47, 49].

An observational study on almost 32,000 people undergoing stomach and bowel surgery showed that those infused with 0.9% salt were more likely to require a blood transfusion [31].

Limited evidence shows that high-chloride fluids may increase hospital stay and in-hospital complications, but more data are needed.

Factors that May Decrease Blood Chloride

The most important thing is to work with your doctor to treat any underlying conditions causing your high chloride levels. The additional strategies below are other things that you may try if you and your doctor determine that they could be appropriate.

1) Staying Hydrated

If high blood chloride concentration is caused by dehydration, restore water levels by drinking abundant water, infusing balanced or chloride-free electrolyte solutions, and avoiding drinking alcohol [3, 61, 62].

2) Certain Medications

Note: By writing this section, we are not recommending changes in your medication schedule. We are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.

The following medications may cause increased blood chloride levels:

  • Diuretics [63, 64]
  • Laxatives [65]
  • Corticosteroids (short-term treatments) [66]
  • Carbonic anhydrase blockers [67]

3) Treating Certain Disorders

Because they can enhance chloride (and other electrolyte) imbalances, the following disorders must be urgently resolved in patients with high blood chloride levels:

  • Diabetes [68]
  • Kidney failure [18]
  • Liver failure [69]
  • Eating disorders (if the patient is abusing laxatives) [70]

Limitations and Caveats

Although the studies covered in this post were mainly human studies, a large number of them were retrospective cohort studies. Because these studies look at existing data, the data may be inaccurate, incomplete, or inconsistently measured. Thus, most of the data collected is only correlational (shows a relationship between the factors) and not causal (determines a cause and effect) [71].

Takeaway

Chloride blood levels above 95-105 mEq in adults and children are considered high (also known as hyperchloremia). This test is usually ordered as part of an electrolyte or metabolic panel.

Symptoms of high chloride levels depend on the underlying cause, such as dehydration or metabolic acidosis. Other potential causes include high salt intake, underlying electrolyte imbalances, and certain genetic disorders.

High chloride levels are not enough for a diagnosis. Your doctor will assess your overall symptoms and lab test results for an accurate diagnosis and treatment.

Further Reading

About the Author

Carlos Tello

Carlos Tello

PhD (Molecular Biology)
Carlos received his PhD and MS from the Universidad de Sevilla.
Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.

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