Electrolytes play a vital role in maintaining homeostasis within the body. They help to regulate myocardial and neurological function, fluid balance, oxygen delivery, acid-base balance and much more

. Electrolyte imbalances can develop by the following mechanisms: excessive ingestion; diminished elimination of an electrolyte; diminished ingestion or excessive elimination of an electrolyte. The most common cause of electrolyte disturbances is renal failure.

The most serious electrolyte disturbances involve abnormalities in the levels of sodium, potassium, and/or calcium.

Table of common electrolyte disturbances

Electrolyte / Ionic formula / Elevation disorder / Depletion disorder
Sodium / Na+ / hypernatremia / hyponatremia
Potassium / K+ / hyperkalemia / hypokalemia
Calcium / Ca2+ / hypercalcemia / hypocalcemia
Magnesium / Mg2+ / hypermagnesemia / hypomagnesemia
Chloride / Cl- / hyperchloremia / hypochloremia
Phosphate / PO43- / hyperphosphatemia / hypophosphatemia
Bicarbonate / HCO3- / hyperbicarbonatemia / hypobicarbonatemia

General Function

Electrolytes are important because they are what cells (especially nerve, heart, muscle) use to maintain voltages across their cell membranes and to carry electrical impulses (nerve impulses, muscle contractions) across themselves and to other cells.

Kidneys work to keep the electrolyte concentrations in blood constant despite changes in your body. For example, during heavy exercise, electrolytes are lost in sweat, particularly sodium and potassium. These electrolytes must be replaced to keep the electrolyte concentrations of the body fluids constant.

Electrolyte abnormalities and ECG changes

  • Potassium
  • The most notable feature of hyperkalemia is the "tent shaped" or "peaked" T wave. Delayed ventricular depolarization leads to a widened QRS complex and the P wave becomes wider and flatter.
  • When hyperkalemia becomes severe, the ECG resembles a sine wave as the P wave disappears from view.
  • In contrast, hypokalemia is associated with flattening of the T wave and the appearance of a U wave. When untreated, hypokalemia may lead to severe arrhythmias.
  • Calcium
  • The fast ventricular depolarization and repolarization associated with hypercalcemia lead to a characteristic shortening of the QT interval.
  • Hypocalcemia has the opposite effect, lengthening the QT interval.

For acidosis referring to acidity of the urine, see renal tubular acidosis.

Acidosis is an increased acidity (i.e. an increased hydrogen ionconcentration). If not further qualified, it usually refers to acidity of the blood plasma.

Acidosis is said to occur when arterial pH falls below 7.35, while its counterpart (alkalosis) occurs at a pH over 7.45.

Arterial blood gas analysis and other tests are required to separate the main causes.

The term acidemia describes the state of low blood pH, while acidosis is used to describe the processes leading to these states. Nevertheless, physicians sometimes use the terms interchangeably. The distinction may be relevant where a patient has factors causing both acidosis and alkalosis, where the relative severity of both determines whether the result is a high or a low pH.

The rate of cellular metabolic activity affects and, at the same time, is affected by the pH of the body fluids

General symptoms of acidosis. These usually accompany symptoms of another primary defect (respiratory or metabolic).

Metabolic acidosis

Metabolic acidosis is an increased production of metabolic acids, usually resulting from disturbances in the ability to excrete acid via the kidneys. Renal acidosis is associated with an accumulation of urea and creatinine as well as metabolic acid residues of protein catabolism.

An increase in the production of other acids may also produce metabolic acidosis. For example, lactic acidosis may occur from 1) severe (PaO2 <36mm Hg) hypoxemia causing a fall in the rate of oxygen diffusion from arterial blood to tissues, or 2) hypoperfusion (e.g. hypovolemic shock) causing an inadequate blood delivery of oxygen to tissues. A rise in lactate out of proportion to the level of pyruvate, e.g. in mixed venous blood, is termed "excess lactate", and may also be an indicator of fermention due to anaerobic metabolism occurring in muscle cells, as seen during strenuous exercise. Once oxygenation is restored, the acidosis clears quickly. Another example of increased production of acids occurs in starvation and diabetic acidosis. It is due to the accumulation of ketoacids (ketosis) and reflects a severe shift from glycolysis to lipolysis for energy needs.

Acid consumption from poisoning, elevated levels of iron in the blood, and chronically decreased production of bicarbonate may also produce metabolic acidosis.

Metabolic acidosis is compensated for in the lungs, as increased exhalation of carbon dioxide promptly shifts the buffering equation to reduce metabolic acid. This is a result of stimulation to chemoreceptors which increases alveolar ventilation, leading to respiratory compensation, otherwise known as Kussmaul breathing (a specific type of hyperventilation). Should this situation persist the patient is at risk for exhaustion leading to respiratory failure.

Mutations to the V-ATPase 'a4' or 'B1' isoforms result in distal renal tubular acidosis, a condition that leads to metabolic acidosis, in some cases with sensorineural deafness.

Arterial blood gases will indicate low pH, low blood HCO3, and normal or low PaCO2. In addition to arterial blood gas, an anion gap can also differentiate between possible causes.

The Henderson-Hasselbalch equation is useful for calculating blood pH, because blood is a buffer solution. The amount of metabolic acid accumulating can also be quantitated by using buffer base deviation, a derivative estimate of the metabolic as opposed to the respiratory component. In hypovolemic shock for example, approximately 50% of the metabolic acid accumulation is lactic acid, which disappears as blood flow and oxygen debt are corrected.

Treatment of uncompensated metabolic acidosis is focused upon correcting the underlying problem. When metabolic acidosis is severe and can no longer be compensated for adequately by the lungs, neutralizing the acidosis with infusions of bicarbonate may be required.

Respiratory acidosis

Respiratory acidosis results from a build-up of carbon dioxide in the blood (hypercapnia) due to hypoventilation. It is most often caused by pulmonary problems, although head injuries, drugs (especially anaesthetics and sedatives), and brain tumors can cause this acidemia. Pneumothorax, emphysema, chronic bronchitis, asthma, severe pneumonia, and aspiration are among the most frequent causes. It can also occur as a compensatory response to chronic metabolic alkalosis.

One key to distinguish between respiratory and metabolic acidosis is that in respiratory acidosis, the CO2 is increased while the bicarbonate is either normal (uncompensated) or increased (compensated). Compensation occurs if respiratory acidosis is present, and a chronic phase is entered with partial buffering of the acidosis through renal bicarbonate retention.

However, in cases where chronic illnesses which compromise pulmonary function persist, such as late-stage emphysema and certain types of muscular dystrophy, compensatory mechanisms will be unable to reverse this acidotic condition. As metabolic bicarbonate production becomes exhausted, and extraeneous bicarbonate infusion can no longer reverse the extreme buildup of carbon dioxide associated with uncompensated respiratory acidosis, mechanical ventilation will usually be applied.

Alkalosis

Alkalosis refers to a condition reducing hydrogen ion concentration of arterialblood plasma (alkalemia). Generally alkalosis is said to occur when pH of the blood exceeds 7.45. The opposite condition is acidosis.

Types

More specifically, alkalosis can refer to:

  • Respiratory alkalosis
  • Metabolic alkalosis

Causes

The main cause of respiratory alkalosis is hyperventilation, resulting in a loss of carbon dioxide. Compensatory mechanisms for this would include increased dissociation of the carbonic acid buffering intermediate into hydrogen ions, and the related excretion of bicarbonate,[citation needed] both of which would lower blood pH.

Metabolic alkalosis can be caused by prolonged vomiting, resulting in a loss of hydrochloric acid with the stomach content. Severe dehydration, and the consumption of alkali are other causes. It can also be caused by administration of diuretics and endocrine disorders such as Cushing's syndrome. Compensatory mechanism for metabolic alkalosis involve slowed breathing by the lungs to increase serum carbon dioxide, a condition leaning toward respiratory acidosis. As respiratory acidosis often accompanies the compensation for metabolic alkalosis, and vice versa, a delicate balance is created between these two conditions.

Complications

Metabolic alkalosis is usually accompanied with hypokalemia, causing e.g. muscular weakness, myalgia, and muscle cramps (owing to disturbed function of the skeletal muscles), and constipation (from disturbed function of smooth muscles).

It may also cause hypocalcemia. As the pH of blood increases, the protein in the blood becomes more ionised into anions. This causes the free calcium present in blood to bind strongly with protein. If severe, it may cause tetany (alkalotic tetany).

Respiratory alkalosis

Respiratory alkalosis is a medical condition in which increased respiration (hyperventilation) elevates the blood pH (a condition generally called alkalosis). It is one of four basic categories of disruption of acid-base homeostasis.

Types

There are two types of respiratory alkalosis: chronic and acute.

  • Acute respiratory alkalosis occurs rapidly. During acute respiratory alkalosis, the person may lose consciousness where the rate of ventilation will resume to normal.
  • Chronic respiratory alkalosis is a more long-standing condition. For every 10 mM drop in pCO2 in blood, there is a corresponding 5 mM of bicarbonate ion drop. The drop of 5 mM of bicarbonate ion is a compensation effect which reduces the alkalosis effect of the drop in pCO2 in blood. This is termed metabolic compensation.

Mechanism

Respiratory alkalosis generally occurs when some stimulus (see "Causes" below) makes a person hyperventilate. The increased breathing produces increased alveolar respiration, expelling CO2 from the circulation. This alters the dynamic chemical equilibrium of carbon dioxide in the circulatory system, and the system reacts according to Le Chatelier's principle. Circulating hydrogen ions and bicarbonate are shifted through the carbonic acid (H2CO3) intermediate to make more CO2 via the enzyme carbonic anhydrase according to the following reaction:

The net result of this is decreased circulating hydrogen ion concentration, and thus increased pH (alkalosis). There is also a decrease in ionized blood calcium concentration.

Causes

Respiratory alkalosis may be produced accidentally by doctors (iatrogenically) during excessive mechanical ventilation. Other causes include:

  • psychiatric causes: anxiety, hysteria and stress
  • CNS causes: stroke, subarachnoid haemorrhage, meningitis
  • drug use: doxapram, aspirin, caffeine and coffee abuse
  • moving into high altitude areas, where the low atmospheric pressure of oxygen stimulates increased ventilation
  • lung disease such as pneumonia, where a hypoxic drive governs breathing more than CO2 levels (the normal determinant)
  • fever, which stimulates the respiratory centre in the brainstem
  • pregnancy
  • sexual activity, which may induce excessive breathing due to excitation

Symptoms

Symptoms of respiratory alkalosis are related to the decreased blood carbon dioxide levels, and include peripheral paraesthesiae. In addition, the alkalosis may disrupt calcium ion balance, and cause the symptoms of hypocalcaemia (such as tetany and fainting) with no fall in total serum calcium levels.

Metabolic alkalosis

Metabolic alkalosis is a metabolic condition in which the pH of the blood is elevated beyond the normal range ( 7.35-7.45 ). This is usually the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations.

Causes

There are five main causes of metabolic alkalosis

These can be divided into two categories, depending upon urine chloride levels.

Chloride-responsive (<10 mEq/L)

  • Loss of hydrogen ions - Most often occurs via two mechanisms, either vomiting or via the kidney.
  • Vomiting results in the loss of hydrochloric acid with the stomach content. To make stomach acid, body moves hydrogen ions from blood to the stomach, causing low hydrogen ions in blood, raising pH of the blood.
  • Renal losses of hydrogen ions occurs when excess aldosterone induces the retention of sodium and hence the excretion of hydrogen from blood to urine, causing low hydrogen ions in blood, raising pH of the blood.
  • Contraction alkalosis - This results from a loss of water in the extracellular space which is poor in bicarbonate, typically from diuretic use. Since water is lost while bicarbonate is retained, the concentration of bicarbonate increases blood pH.

Chloride-resistant (>20 mEq/L)

  • Retention of bicarbonate
  • Shift of hydrogen ions into intracellular space - Seen in hypokalemia. Due to a low extracellular potassium concentration, potassium shifts out of the cells. In order to maintain electrical neutrality, hydrogen shifts into the cells, raising blood pH.
  • Alkalotic agents - Alkalotic agents, such as bicarbonate (administrated in cases of peptic ulcer or hyperacidity) or antacids, administered in excess can lead to an alkalosis.

Compensation

Compensation for metabolic alkalosis occurs mainly in the lungs, which retain carbon dioxide (CO2) through slower breathing, or hypoventilation (respiratory compensation). CO2 is then consumed toward the formation of the carbonic acid intermediate, thus decreasing pH. Respiratory compensation, though, is incomplete. The decrease in [H+] suppresses the peripheral chemoreceptors, which are sensitive to pH. But, because respiration slows, there's an increase in Pco2 which would cause an offset of the depression because of the action of the central chemoreceptors which are sensitive to the partial pressure of CO2 in the blood. So, because of the central chemoreceptors, respiration rate would be increased.

Renal compensation for metabolic alkalosis, less effective than respiratory compensation, consists of increased excretion of HCO3- (bicarbonate), as the filtered load of HCO3- exceeds the ability of the renal tubule to reabsorb it.

Hypokalemia

Hypokalemia (refers to the condition in which the concentration of potassium (K+) in the blood is low. Normal serum potassium levels are between 3.5 to 5.0 mEq/L ,at least 95% of the body's potassium is found inside cells, with the remainder in the blood. This concentration gradient is maintained principally by the Na+/K+ pump.

Signs and symptoms

Mild hypokalemia is often without symptoms, although it may cause a small elevation of blood pressure, and can occasionally provoke cardiac arrhythmias.

Moderate hypokalemia, with serum potassium concentrations of 2.5-3 mEq/L, may cause muscular weakness, myalgia, and muscle cramps (owing to disturbed function of the skeletal muscles), and constipation (from disturbed function of smooth muscles). With more severe hypokalemia, flaccid paralysis, hyporeflexia, and tetany may result. There are reports of rhabdomyolysis occurring with profound hypokalemia with serum potassium levels less than 2 mEq/L. Respiratory depression from severe impairment of skeletal muscle function is found in many patients.

Some electrocardiographic (ECG) findings associated with hypokalemia are flattened T waves and prolongation of the QT interval. The prolonged QT interval may lead to arrhythmias.

Hyperkalemia

Hyperkalemia (hyper- high; kalium, potassium; -emia, "in the blood") is an elevated blood level of the electrolytepotassium. Extreme hyperkalemia is a medical emergency due to the risk of potentially fatal abnormal heart rhythms (arrhythmia).

Signs and symptoms

Symptoms are fairly nonspecific and generally include malaise, palpitations and muscle weakness; mild hyperventilation may indicate a compensatory response to metabolic acidosis, which is one of the possible causes of hyperkalemia. Often, however, the problem is detected during screening blood tests for a medical disorder, or it only comes to medical attention after complications have developed, such as cardiac arrhythmia or sudden death.

During the medical history taking, a physician will dwell on kidney disease and medication use (see below), as these are the main causes. The combination of abdominal pain, hypoglycemia and hyperpigmentation, often in the context of a history of other autoimmune disorders, may be signs of Addison's disease, itself a medical emergency.

Diagnosis

In order to gather enough information for diagnosis, the measurement of potassium needs to be repeated, as the elevation can be due to hemolysis in the first sample. The normal serum level of potassium is 3.5 to 5 mEq/L. Generally, blood tests for renal function (creatinine, blood urea nitrogen), glucose and occasionally creatine kinase and cortisol will be performed. Calculating the trans-tubular potassium gradient can sometimes help in distinguishing the cause of the hyperkalemia.

In many cases, renal ultrasound will be performed, since hyperkalemia is highly suggestive of renal failure.

Also, electrocardiography (EKG/ECG) may be performed to determine if there is a significant risk of cardiac arrhythmias (see ECG/EKG Findings, below).

Differential diagnosis

Causes include:

Ineffective elimination from the body

  • Renal insufficiency
  • Medication that interferes with urinary excretion:
  • ACE inhibitors and angiotensin receptor blockers
  • Potassium-sparing diuretics (e.g. amiloride and spironolactone)
  • NSAIDs such as ibuprofen, naproxen, or celecoxib
  • The calcineurin inhibitor immunosuppressants ciclosporin and tacrolimus
  • The antibiotic trimethoprim
  • The antiparasitic drug pentamidine
  • Mineralocorticoid deficiency or resistance, such as:
  • Addison's disease
  • Aldosterone deficiency, including reduced levels due to the blood thinner, heparin
  • Some forms of congenital adrenal hyperplasia
  • Type IV renal tubular acidosis (resistance of renal tubules to aldosterone)
  • Gordon's syndrome (“familial hypertension with hyperkalemia”), a rare genetic disorder caused by defective modulators of salt transporters, including the thiazide-sensitive Na-Cl cotransporter.

Excessive release from cells

  • Rhabdomyolysis, burns or any cause of rapid tissue necrosis, including tumor lysis syndrome
  • Massive blood transfusion or massive hemolysis
  • Shifts/transport out of cells caused by acidosis, low insulin levels, beta-blocker therapy, digoxin overdose, or the paralyzing agent succinylcholine

Excessive intake

  • Intoxication with salt-substitute, potassium-containing dietary supplements, or potassium chloride (KCl) infusion. Note that for a person with normal kidney function and nothing interfering with normal elimination (see above), hyperkalemia by potassium intoxication would be seen only with large infusions of KCl or oral doses of several hundred millequivalents of KCl.[1]

Lethal injection

Hyperkalemia is intentionally brought about in an execution by lethal injection, with potassium chloride being the third and last of the three drugs administered to cause death.

Pseudohyperkalemia

Pseudohyperkalemia is a rise in the amount of potassium that occurs due to excessive leakage of potassium from cells, during or after blood is drawn. It is a laboratory artifact rather than a biological abnormality and can be misleading to caregivers.[2] Pseudohyperkalemia is typically caused by hemolysis during venipuncture (by either excessive vacuum of the blood draw or by a collection needle that is of too fine a gauge); excessive tourniquet time or fist clenching during phlebotomy (which presumably leads to efflux of potassium from the muscle cells into the bloodstream);[3] or by a delay in the processing of the blood specimen. It can also occur in specimens from patients with abnormally high numbers of platelets (>1,000,000/mm³), leukocytes (> 100 000/mm³), or erythrocytes (hematocrit > 55%). People with "leakier" cell membranes have been found, whose blood must be separated immediately to avoid pseudohyperkalemia.[4]