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Hypochloremia

Hypochloremia

Chloride is an electrolyte, an anion present in all body fluids but is found in the highest concentration in the blood and in the fluid outside of the body’s cells (extracellular fluid or ECF). Chloride is a negatively charged ion that works with other electrolytes, such as potassium, sodium, and bicarbonate, to help regulate the amount of fluid in the body and maintain the acid-base balance. The kidneys predominantly regulate serum chloride level. Most of the chloride which is filtered by the glomerulus is reabsorbed by both proximal and distal tubules (majorly by proximal tubule) by both active and passive transport 1.

There are no established cut-off values for hypochloremia, normochloremia, or hyperchloremia 2; most studies use cut-off values of < 98 mEq/L for hypochloremia and > 110 mEq/L for hyperchloremia 3.

Hypochloremia is usually caused by excess use of loop diuretics, nasogastric suction, excess water gain like congestive heart failure or vomiting. Metabolic alkalosis is usually present with hypochloremia. Vomiting causes loss of hydrochloric acid. In the presence of extracellular fluid volume contraction, there is an increase in sodium (Na) and bicarbonate (HCO3−) resorption in the kidney, which helps to maintain the alkalosis. Aldosterone accelerates the retention of sodium and HCO3− at the expense of hydrogen, potassium (K), and chloride.

Most of the time, chloride concentrations mirror those of sodium, increasing and decreasing for the same reasons and in direct relationship to sodium. When there is an acid-base imbalance, however, blood chloride levels can change independently of sodium levels as chloride acts as a buffer. It helps to maintain electrical neutrality at the cellular level by moving into or out of the cells as needed.

You get chloride in your diet through food and table salt, which is made up of sodium and chloride ions. Most of the chloride is absorbed by the digestive tract, and the excess is eliminated in urine. The normal blood level remains steady, with a slight drop after meals because the stomach produces acid after eating, using chloride from blood.

Hypochloremia causes

Hypochloremia may be due to 4, 5:

  • Addison disease
  • Adrenal insufficiency
  • Bartter syndrome
  • Burns
  • Congestive heart failure
  • Cirrhosis of the liver
  • Nephrotic syndrome
  • Emphysema or other chronic lung diseases (causing respiratory acidosis)
  • Excessive sweating
  • Hyperaldosteronism
  • Metabolic alkalosis
  • Respiratory acidosis (compensated)
  • Syndrome of inappropriate diuretic hormone secretion (SIADH)
  • Vomiting
  • Diarrhea
  • Nasogastric suction
  • Small bowel fistulas
  • Renal failure combined with salt deprivation
  • Intrinsic renal diseases
  • Over treatment with diuretics
  • Chronic respiratory acidosis
  • Diabetic ketoacidosis
  • Hypothyroidism
  • Salt-losing nephropathy e.g., interstitial nephritis
  • Acute intermittent porphyria
  • Water intoxication or pathologic water drinkers
  • Expansion of extracellular fluid volume
  • Inadequate sodium chloride (NaCl) intake
  • Increased effective circulatory blood volume:
    • Hypertonic infusions
    • Hyperglycemia (early stages)
  • Use of certain drugs 6:
    • Chronic laxative
    • Bicarbonate ingestion
    • Corticosteroids
    • Diuretics
    • Barbiturates
    • Chlorpropramide
    • Clofibrate
    • Morphine
    • Nicotine
    • Tricyclics

Total body chloride depletion can result from both extrarenal and renal causes 6. Extrarenal causes include inadequate sodium chloride intake, losses of certain gastrointestinal fluids (e.g., vomiting and nasogastric suction associated with loss of HCl, or diarrhea as a result of abnormalities in small bowel transport), and loss of fluids through the skin occurring as a result of trauma (e.g., burns). Severe vomiting may lead to the most disproportionate loss of chloride compared to sodium since gastric chloride content is greater than 100 mEq/L and gastric sodium content is relatively low (20 to 30 mEq/L). In individuals with protracted vomiting or nasogastric suction, the serum sodium concentration may be only mildly depressed (130 mEq/L), whereas the serum chloride concentration is usually markedly lowered (80 to 90 mEq/L). The most reduced levels of serum chloride (range 45 to 70 mEq/L) are associated with pernicious forms of vomiting due to gastric outlet obstruction, protracted vomiting in alcoholics, or self-induced vomiting. Individuals with hypochloremia secondary to total body chloride depletion will have physical findings that indicate extracellular fluid volume contraction (e.g., hypotension, tachycardia, and orthostatic changes in blood pressure). Further support of total body chloride (and sodium) depletion is the finding of low concentrations of sodium and chloride in the urine. Renal causes of chloride (and sodium) losses include diuretic abuse, particularly loop diuretics; osmotic diuresis (e.g., mannitol, diabetic ketoacidosis, or hyperosmolar nonketotic coma); renal diseases associated with a salt-losing nephropathy including interstitial nephritis; chronic renal failure; postobstructive diuresis; and conditions associated with adrenal insufficiency (e.g.. lack of endogeneous or exogeneous glucocorticoids or mineralocorticoids). The physical findings in individuals with hypochloremia as a result of renal losses of sodium and chloride will be similar to individuals with extrarenal chloride losses. In these individuals, however, the concentration of chloride and sodium in the urine will be elevated, indicating renal losses of chloride (and sodium) despite evidence of extracellular fluid volume contraction.

Another finding often associated with total chloride depletion is metabolic alkalosis (blood pH greater than 7.45). The reabsorption of sodium bicarbonate (NaHCO3) in the proximal and distal tubule is augmented because total body chloride depletion results in both extracellular fluid volume contraction (which stimulates HCO3 reabsorption) and decreased quantities of filtered chloride available to the tubules for reabsorption with sodium. The virtual absence of chloride in the urine in the presence of a metabolic alkalosis is a strong indication that total body chloride depletion is present. Augmented reabsorption of NaHCO3 will persist until adequate quantities of chloride are administered and/or the volume of the extracellular fluid compartment is normalized. Metabolic alkalosis also increases potassium excretion by the kidneys which can lead to hypokalemia.

A number of chloride-containing solutions can be used to correct total body chloride depletion including isotonic sodium chloride (normal saline, physiologic saline) for replacement of just sodium and chloride; potassium chloride for replacement of potassium and chloride; and lysine monochloride, arginine monochloride, ammonium chloride, or HCl when acid replacement is necessary in conditions associated with chloride depletion and severe metabolic alkalosis.

Clinical conditions associated with excess water retention can cause a dilutional hyponatremia with a proportionate decrease in the chloride concentration 6. This form of hypochloremia does not reflect total body chloride or sodium depletion, and, in fact, many of the conditions associated with dilutional hypochloremia have a normal or increased total body content of chloride and sodium. Individuals with dilutional hypochloremia generally have a normal or elevated blood pressure and evidence of extracellular fluid volume expansion. The sodium and chloride urine concentrations are variable depending on the underlying medical condition.

Specific acid–base abnormalities may also be associated with hypochloremia. Conditions associated with a respiratory acidosis (e.g., retention of CO2 as with chronic obstructive lung disease) cause the proximal tubule to increase its secretion of hydrogen ion. This results in sodium being retained prefentially as sodium bicarbonate and not sodium chloride. Although this is a compensatory mechanism to help ameliorate the acidemia, the end result is increased concentrations of serum bicarbonate (greater than 30 mEq/L) and decreased serum chloride concentrations. Conditions causing dilutional hyponatremia and hypochloremia do not require chloride-containing fluids, since they do not have total body chloride depletion. However, respiratory acidosis associated with hypochloremia may need chloride-containing fluids if a metabolic alkalosis and/or hypokalemia is also present.

Hypochloremia signs and symptoms

There are no specific signs or symptoms of hypochloremia 7. Hypochloremia signs and symptoms depend on the underlying cause. Hypochloremia can result in hyperirritability, tetany or muscular excitability, slowed respirations and hypotension secondary to fluid loss 8.

Hypochloremia can occur in a wide variety of conditions, including vomiting, diarrhea, gastrointestinal suction, renal failure combined with salt deprivation, overtreatment with diuretics, chronic respiratory acidosis, diabetic ketoacidosis, excessive sweating, syndrome of inappropriate antidiurectic hormone excretion (SIADH), salt-losing nephropathy, acute intermittent porphyria, water intoxication, expansion of extracellular fluid volume, adrenal insufficiency, hyperaldosteronism, metabolic alkalosis, and the use of certain drugs like chronic laxative or bicarbonate ingestion, corticosteroids, and diuretics 4, 5.

Hypochloremia diagnosis

A chloride blood test is used to detect hypochloremia. It is often used, along with other electrolytes, as part of a routine health exam to screen for a variety of conditions.

Chloride and other electrolyte tests may also be used to help diagnose the cause of signs and symptoms such as prolonged vomiting, diarrhea, weakness, and difficulty breathing (respiratory distress). If an electrolyte imbalance is detected, your healthcare practitioner will look for and address the disease, condition, or medication causing the imbalance and may use a series of electrolyte tests to monitor the effectiveness of treatment. If an acid-base imbalance is suspected, your healthcare practitioner may also order tests for blood gases to further evaluate the severity and cause of the imbalance.

Urine chloride tests may be used by your healthcare practitioner to determine whether the cause of alkalosis (too much base) is loss of salt (in cases of dehydration, vomiting, or use of diuretics, where urine chloride would be very low) or an excess of certain hormones such as cortisol or aldosterone that can affect electrolyte elimination.

The diagnosis of hypochloremia is made based on the patient’s history of diuretic therapy, vomiting, or nasogastric suctioning along with the assessment of chloride values in the presence of metabolic alkalosis. If urine chloride is less than 10 mEq/L, then hypochloremia is due to chloride responsive alkalosis. If greater than 40 mEq/L, hypochloremia is due to volume overload or dilution. These patients usually have a metabolic alkalosis due to excess mineralocorticoid or glucocorticoid.

Hypochloremia treatment

Hypochloremia treatment involves treating the underlying cause. Chloride‐responsive alkalosis is treated with normal saline. Chloride‐resistant metabolic alkalosis requires IV normal saline plus K. Give one fourth as KCl and three fourths as NaCl.

Chloride is readily available in the food supply and most Americans probably consume more than necessary, in the form of table salt and salt in prepared foods. It is also found in many vegetables and in foods such as salted meats, butter, tomatoes, lettuce, celery, and olives.

References
  1. Morrison G. Serum Chloride. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Butterworths; Boston: 1990.
  2. Neyra JA, et al. Association of Hyperchloremia With Hospital Mortality in Critically Ill Septic Patients. Crit Care Med. 2015;43:1938–1944. doi: 10.1097/CCM.0000000000001161
  3. Kimura S, et al. Association of serum chloride concentration with outcomes in postoperative critically ill patients: a retrospective observational study. J Intensive Care. 2014;2:39. doi: 10.1186/2052-0492-2-39
  4. Nicoll Diana, McPhee Stephen J, Pignone Michael, Lee Chuenyi Mark. Pocket guide to Diagnostic tests. 5th Edition.
  5. Jacques Wallach. Interpretation of Diagnostic Tests. 8th Edition. Lippincott Williams & Wilkins
  6. Morrison G. Serum Chloride. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 197. Available from: https://www.ncbi.nlm.nih.gov/books/NBK309
  7. Essential Emergency Medicine For the Healthcare Practitioner 2007. ISBN 978-1-4160-2971-7 https://doi.org/10.1016/B978-1-4160-2971-7.X1000-8
  8. Delmar’s Guide to Laboratory and Diagnostic Tests. 2nd Edition (2010).
Health Jade Team

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