Electrolyte Balance – Pathophysiology, Mechanism, Importance

Sodium, Electrolytes, and Fluid Balance

Electrolytes play a vital role in maintaining homeostasis within the body.

Importance of Electrolyte Balance

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

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

Electrolyte imbalances can develop from excessive or diminished ingestion and from the excessive or diminished 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.

Other electrolyte imbalances are less common and often occur in conjunction with major electrolyte changes. Chronic laxative abuse or severe diarrhea or vomiting (gastroenteritis) can lead to electrolyte disturbances combined with dehydration. People suffering from bulimia or anorexia nervosa are especially at high risk for an electrolyte imbalance.

Kidneys work to keep the electrolyte concentrations in blood constant despite changes in your body. For example, during heavy exercise electrolytes are lost through sweating, particularly sodium and potassium, and sweating can increase the need for electrolyte (salt) replacement. It is necessary to replace these electrolytes to keep their concentrations in the body fluids constant.

Dehydration

There are three types of dehydration:

• Hypotonic or hyponatremic (primarily a loss of electrolytes, sodium in particular).
• Hypertonic or hypernatremic (primarily a loss of water).
• Isotonic or hyponatremic (an equal loss of water and electrolytes).

In humans, the most common type of dehydration by far is isotonic (isonatraemic) dehydration; which effectively equates with hypovolemia; but the distinction of isotonic from hypotonic or hypertonic dehydration may be important when treating people with dehydration.

Physiologically, and despite the name, dehydration does not simply mean loss of water, as both water and solutes (main sodium) are usually lost in roughly equal quantities as to how they exist in blood plasma. In hypotonic dehydration, intravascular water shifts to the extravascular space and exaggerates the intravascular volume depletion for a given amount of total body water loss.

Neurological complications can occur in hypotonic and hypertonic states. The former can lead to seizures, while the latter can lead to osmotic cerebral edema upon rapid rehydration.

In more severe cases, the correction of a dehydrated state is accomplished by the replenishment of necessary water and electrolytes (through oral rehydration therapy or fluid replacement by intravenous therapy). As oral rehydration is less painful, less invasive, less expensive, and easier to provide, it is the treatment of choice for mild dehydration. Solutions used for intravenous rehydration must be isotonic or hypotonic.

Sodium Balance Regulation

Sodium is an important cation that is distributed primarily outside the cell.

Sodium Regulation

Sodium is an important cation that is distributed primarily outside the cell. The cell sodium concentration is about 15 mmol/l, but it varies in different organs; it has an intracellular volume of 30 liters and about 400 mmol are inside the cell.

The plasma and interstitial sodium is about 140 mmol/l with an extracellular volume of about 13 liters, 1,800 mmol are in the extracellular space. The total body sodium, however, is about 3,700 mmol as there is about 1,500 mmol stored in bones.

The body has potent sodium-retaining mechanisms and even if a person is on five mmol Na+/day they can maintain sodium balance. Extra sodium is lost from the body by reducing the activity of the renin –angiotensin system that leads to increased sodium loss from the body. Sodium is lost through the kidneys, sweat, and feces.

In states of sodium depletion, the aldosterone levels increase. In states of sodium excess, aldosterone levels decrease. The major physiological controller of aldosterone secretion is the plasma angiotensin II level that increases aldosterone secretion.

A high plasma potassium level also increases aldosterone secretion because, besides retaining Na+, high plasma aldosterone causes K+ loss by the kidney. Plasma Na+ levels have little effect on aldosterone secretion.

A low renal perfusion pressure stimulates the release of renin, which forms angiotensin I that is converted to angiotensin II. Angiotensin II will correct the low perfusion pressure by causing the blood vessels to constrict, and increase sodium retention by its direct effect on the proximal renal tubule and by an effect operated through aldosterone. The perfusion pressure to the adrenal gland has a little direct effect on aldosterone secretion and the low blood pressure operates to control aldosterone via the renin-angiotensin system.

Aldosterone also acts on the sweat ducts and colonic epithelium to conserve sodium. When aldosterone is activated to retain sodium the plasma sodium tends to rise. This immediately causes the release of ADH, which causes water to be retained, thus balancing Na+ and H2O in the right proportion to restore plasma volume.

In addition to aldosterone and angiotensin II, other factors influence sodium excretion.

• Atrial peptide causes the loss of sodium by the kidneys: it is secreted from the heart in high sodium states due to excess intake or cardiac disease.
• Elevated blood pressure will also cause Na+ loss, and low blood pressure usually leads to sodium retention.

Potassium Balance Regulation

Potassium is mainly an intracellular ion.

Potassium Balance

Potassium is predominantly an intracellular ion. Most of the total body potassium of about 4,000 mmol is inside the cells, and the next largest proportion (300–500 mmol) is in the bones. Cell K+ concentration is about 150 mmol/l but varies in different organs. Extracellular potassium is about 4.0 mmol/l, with an extracellular value of about 13 liters, 52 mmol (i.e., less than 1.5%) is present here and only 12 mmol is in the plasma.

In an unprocessed diet, potassium is much more plentiful than sodium. It is present as an organic salt, while sodium is added as NaCl. In a hunter-gatherer, K+ intake may be as much as 400 mmol/d while in the Western diet it is 70 mmol/d or less if a person has a minimal amount of fresh fruit and vegetables.

The processing of foods replaces K+ with NaCl. While the body can excrete a large K+ load, it is unable to conserve K+. On a zero K+ intake, or in a person with K+ depletion, there will still be a loss of K+ of 30–50 mmol/d in the urine and feces.

Acid-Base Status Control

If there is a high potassium intake, for example, 100 mmol, this would potentially increase the extracellular K+ level two times before the kidney could excrete the extra potassium. The body buffers the extra potassium by equilibrating it within the cells.

The acid-base status controls the distribution between plasma and cells. A high pH (i.e., alkalosis >7.4) favors the movement of K+ into the cells, and a low pH (i.e., acidosis ) causes movement out of the cell. A high plasma potassium level increases aldosterone secretion and this increases the potassium loss from the body to restore balance.

This change of distribution with the acid-base status means that the plasma K+ may not reflect the total body content. Therefore, a person with acidosis (pH 7.1) and a plasma K+ of 6.5 mmol/l could be depleted of total body potassium. This occurs in diabetic acidosis. Conversely, a person who is alkalotic with a plasma K+ of 3.4 mmol/l may have a normal level of total body potassium.

Calcium and Phosphate Balance Regulation

Calcium is a key electrolyte: 99% is deposited in the bones and the remainder is associated with hormone release and cell signaling.

Calcium is a very important electrolyte. Ninety-nine percent or more is deposited in the bones and the remainder plays a vital role in nerve conduction, muscle contraction, hormone release, and cell signaling.

The plasma concentration of Ca++ is 2.2 mmol/l, and phosphate is 1.0 mmol/l. The solubility product of Ca and P is close to saturation in plasma. The concentration of Ca++ in the cytoplasm is < 10–6 mmol/l but the concentration of Ca++ in the cell is much higher as calcium is taken up (and is able to be released from) cell organelles.

In the typical Australian diet, there is about 1200 mg/d of calcium. Even if it was all soluble it is not all absorbed as it combines with phosphates in the intestinal secretions. In addition, absorption is regulated by the active vitamin D; increased amounts of vitamin D increase Ca++ absorption.

Absorption is controlled by vitamin D while excretion is controlled by parathyroid hormones. However, the distribution from bone to plasma is controlled by both the parathyroid hormones and vitamin D.

There is also a constant loss of calcium via the kidneys even if there is none in the diet. This excretion of calcium by the kidneys and its distribution between bone and the rest of the body is primarily controlled by the parathyroid hormone.

The calcium in plasma exists in three forms:

1. Ionized.
2. Nonionized.
3. Protein-bound.

It is the ionized calcium concentration that is monitored by the parathyroid gland —if it is low, parathyroid hormone secretion is increased. This increases the ionized calcium levels by increasing bone re-absorption, decreasing renal excretion, and acting on the kidney to increase the rate of formation of active vitamin D, thereby increasing the gut’s absorption of calcium.

The usual amount of phosphate in the diet is about 1 g/d but not all of it is absorbed. Any excess is excreted by the kidney and this excretion is increased by the parathyroid hormone.

This hormone also causes phosphate to leach out of the bones. Plasma phosphate has no direct effect on parathyroid hormone secretion; however, if it is elevated it combines with Ca++ to decrease ionized Ca++ in plasma, and thereby increase parathyroid hormone secretion.

Anion Regulation

The anions chloride, bicarbonate, and phosphate have important roles in maintaining the balance and neutrality of vital body mechanisms.

Anion Regulation

The excretion of ions occurs mainly through the kidneys, with lesser amounts of ions being lost in sweat and in feces. In addition, excessive sweating may cause a significant loss, especially of the anion chloride. Severe vomiting or diarrhea will also cause a loss of chloride and bicarbonate ions.

Adjustments in the respiratory and renal functions allow the body to regulate the levels of these ions in the extracellular fluid (ECF).

Chloride

Chloride is the predominant extracellular anion and it is a major contributor to the osmotic pressure gradient between the intracellular fluid (ICF) and extracellular fluid (ECF). Chloride maintains proper hydration and functions to balance the cations in the ECF to keep the electrical neutrality of this fluid. The paths of secretion and reabsorption of chloride ions in the renal system follow the paths of sodium ions.

Hypochloremia, or lower-than-normal blood chloride levels, can occur because of defective renal tubular absorption. Vomiting, diarrhea, and metabolic acidosis can also lead to hypochloremia.

In contrast, hyperchloremia, or higher-than-normal blood chloride levels, can occur due to dehydration, excessive intake of dietary salt (NaCl) or the swallowing of sea water, aspirin intoxication, congestive heart failure, and the hereditary, chronic lung disease cystic fibrosis. In people who have cystic fibrosis, the chloride levels in their sweat are two to five times those of normal levels; therefore, analysis of their sweat is often used to diagnose the disease.

Bicarbonate

Bicarbonate is the second-most abundant anion in the blood. Its principal function is to maintain your body’s acid–base balance by being part of buffer systems.

Bicarbonate ions result from a chemical reaction that starts with the carbon dioxide (CO₂) and water (H₂O) molecules that are produced at the end of aerobic metabolism. Only a small amount of CO₂ can be dissolved in body fluids; thus, over 90 percent of the CO₂ is converted into bicarbonate ions, HCO₃-, through the following reactions:

CO₂ + H₂O ↔ H₂CO₃ ↔ H₂CO₃– + H+

The bidirectional arrows indicate that the reactions can go in either direction depending on the concentrations of the reactants and products. Carbon dioxide is produced in large amounts in tissues that have a high metabolic rate, and is converted into bicarbonate in the cytoplasm of the red blood cells through the action of an enzyme called carbonic anhydrase.

Bicarbonate is transported in the blood and once in the lungs, the reactions reverse direction, and CO₂ is regenerated from the bicarbonate to be exhaled as metabolic waste.

Phosphate

Phosphate is present in the body in three ionic forms:

1. H₂PO₄−
2. HPO₄²⁻
3. PO₄³⁻

The addition and removal of phosphate from the proteins in all cells is a pivotal strategy in the regulation of metabolic processes. Phosphate is useful in animal cells as a buffering agent, and the most common form is HPO²⁻₄. Bone and teeth bind up 85 percent of the body’s phosphate as part of calcium phosphate salts. In addition, phosphate is found in phospholipids, such as those that make up the cell membrane, and in ATP, nucleotides, and buffers.

Hypophosphatemia, or abnormally low phosphate blood levels, occurs with the heavy use of antacids, during alcohol withdrawal, and during malnourishment. In the face of phosphate depletion, the kidneys usually conserve phosphate, but during starvation, this conservation is impaired greatly.

Hyperphosphatemia, or abnormally increased levels of phosphates in the blood, occurs if there is decreased renal function or in cases of acute lymphocytic leukemia. Additionally, because phosphate is a major constituent of the ICF, any significant destruction of cells can result in the dumping of phosphate into the ECF.