FLUID AND ELECTROLYTE BALANCE PHYSIOLOGY
Cell function depends not only on a continuous supply of nutrients and removal of metabolic wastes, but also on the physical and chemical homeostasis of the surrounding fluids.
Body water content
In a healthy young adult, water probably accounts for about half body weight (mass). However not all bodies contain the same amount of water, and total body water is a function not only of weight, age and sex but also of the relative amount of body fat. Because of their low body fat and low bone mass, infants are 73% or more water.
But total water content declines throughout life, accounting for only about 45% of body weight in old age. A healthy young woman about 50%. This significant difference between the sexes reflects the relatively larger amount of body fat and smaller amount of skeletal muscle in females. Of all body tissues, adipose tissue is least hydrated containing up to 20% water; even bone contains more water than does fat. By contrast, skeletal muscle is about 65% water. Thus, people with greater muscle mass have proportionately more body water.
Water occupies two main fluid compartments within the body. A little less than two-thirds by volume is in the intracellular fluid (ICF) compartment, which actually consists of trillions of tiny individual compartments: the cells. In an adult male of average size (70kg). ICF accounts for about 25L of the 40L of body water. The remaining one-third or so of body water is outside cells, in the extracellular fluid (ECF) compartment. The ECF compartment is, in turn, divisible into two important subcompartments: (1) plasma, the fluid portion of blood within the blood vessels and (2) interstitial fluid (IF), the fluid in the microscopic spaces between tissue cells. Additionally, there are numerous other examples of ECF that are distinct from both plasma and interstitial fluid such as lymph, cerebrospinal fluid, and secretions of the gastrointestinal tract.
In the 70kg adult male, interstitial fluid accounts for approximately 12L and plasma about 3L of total (15L)ECF volume.
Composition of Body Fluids
Solutes: Electrolytes and Nonelectolytes
Water serves as the universal solvent in which a variety of solutes are dissolved. Solutes may be classified broadly as electrolytes and nonelectrolytes. The non electrolytes have bonds that prevent them from dissociating in solution; therefore, they have no electrical charge. Most nonelectrolytes are organic molecules – glucose, lipids, creatinine and urea. In contrast, electrolytes are chemical components that do dissociate into ions in water. Because ions are charged particles, they can conduct an electrical current – hence the name electrolyte. Typically, electrolytes include inorganic salts, both inorganic and organic acids and bases, and some proteins.
Although all dissolved solutes contribute to the osmotic activity of a fluid, electrolytes have much greater osmotic power than nonelectrolytes because each electrolyte molecule dissociates into at least two ions. For example, a molecule of sodium chloride (NaCl) contributes twice as many solute particles as glucose (which remains undissociated), and a molecule of magnesium chloride (MgCl2) contributes three times as many:
NaCl à Na+ + Cl– (two particles)
MgCl2 à Mg2+ + Cl– + Cl– (three particles)
Glucose à glucose (one particle)
Regardless of the type of solute particle, water moves according to osmotic gradients – from areas of lesser osmolality to those of greater osmolality. Thus, electrolytes have the greatest ability to cause fluid shifts.
Electrolyte concentrations of body fluids are usually expressed in milliequivalents per liter (mEq/L), a measure of the number of electrical charges in 1 liter of solution. Because the total number of negative charges (anions) in a solution is always equal to the number of positive charges (cations), the milliequivalent system of reporting electrolyte concentrations makes it easier to follow electrolyte shifts.
The concentration of any ion in solution in mEq/L can be computed using the equation.
Concentration of ion (mg/L)
mEq/L = x No. of electrical charges on one ion
atomic weight of ion
Comparison of Extracellular and Intracellular Fluids
Each fluid compartment has distintictive pattern of electrolytes. But except for the relatively high protein content in plasma, the extracellular fluids are very similar. Their chief caution is sodium, and their major anion is chloride. However, plasma contains somewhat fewer chloride ions than interstitial fluid, because the nonpenetrating plasma proteins are normally anions and plasma is electrically neutral.
In contrast to extracellular fluids, intracellular fluid contains only small amounts of Na+ and Cl–. Its most abundant cation is potassium, and its major anion is phosphate (HPO42-). Cells also contain moderate amounts of magnesium ions and substantial quantities of soluble proteins (about three times the amount found in plasma).
Sodium and potassium ion concentrations in extracellular and intracellular fluids are nearly opposite. The characteristic distribution of these ions on the two sides of cellular membranes reflects the activity of cellular ATP-dependent sodium-potassium pumps, which keep intracellular Na’ concentrations low while maintaining high intracellular K+ concentrations.
Fluid Movement Among Compartments
The continuous exchange and mixing of body fluids are regulated by osmotic and/or hydrostatic pressures. Although water moves freely between the compartments along osmotic gradients, solutes are unequally distributed because of their molecular size, electrical charge, or dependence on active transport.
Exchanges between plasma and interstitial fluid occur across capillary membranes.
Nearly protein-free plasma is forced out of the blood stream into the interstitial space by the hydrostatic pressure of blood. This filtered fluid is almost completely reabsorbed into the bloodstream in response to the colloid osmotic (oncotic) pressure of plasma proteins. Under normal circumstances, the small net leakage that remains behind in the interstitial space is picked up by lymphatic vessels and returned to the bloodstream.
Exchanges between the interstitial and intracellular fluids are more complex because of the selective permeability of cellular membranes. As a general rule, two-way osmotic flows of water are substantial. But ion fluxes are restricted and, in most cases, ions move selectively by active transport. Movements of nutrients, respiratory gases, and wastes are typically unidirectional. For example, glucose and oxygen move into the cells and metabolic wastes move out of the cells and into the blood.
Of the various body fluids, only plasma circulates throughout the body and serves as the link between the external and internal environments. Exchanges occur almost continuously I the lungs, gastrointestinal tract, and kidneys. Although these exchanges alter plasma composition and volume, they are quickly followed by compensating adjustments in the other two fluid compartments so that balance is restored.
Many factors can cause marked changes in ECF and ICF volumes. However, water moves freely between compartments, so the osmolalities of all body fluids are equal, except for the first few minutes after a change in one of the fluids occurs. Increasing the solute content of the ECF (most importantly, the NaCl concentration) can be expected to cause osmotic changes in the ICF-namely, a shift of water out of the cells. Conversely, decreasing the osmolality of the ECF causes water to move into the cells. Thus, the volume of the ICF is determined by the solute concentration of the, ECF.
To remain properly hydrated, water intake must be equal water output Water intake varies Widely from person to person and is strongly influenced by habit, but it is typically about 2500 ml a day in adults. Most water enters the body through ingested liquids (about 60%) and solid foods (about 30%). About 10% of body water is produced by cellular metabolism; this is Called metabolic water or water of oxidation.
Water output occurs by several routes. Some water (28%) vaporizes out of the lungs in expired air or diffuses directly through the skin; this is called insensible water loss. Some, is lost in obvious perspiration (8%) and in feces (4%). The balance (60%) is excreted by the kidneys in urine.
Regulation of Water Intake:
The Thirst Mechanisms
Thirst is the driving force for water intake, but the thirst mechanism is poorly understood It appears that a decrease in plasma volume of 10% (or more, as from hemorrhage) and / or an increase in plasma- osmolality of 1% to 21% results in a dry mouth and excites the hypothalamic thirst center. A dry mouth occurs because the rise in plasma oncotic pressure causes less fluid to leave the bloodstream. Because the salivary glands obtain the water they require from the blood, less saliva is produced. The hypothalamic thirst center, is stimulated when its osmoreceptors lose water by osmosis to the hyportonic ECF, an event that causes them to become irritable and depolarize. Collectively, these events cause a subjective sensation of thirst, which motivates us to get a drink. This mechanism helps explain the nagging thirst of a hemorrhaging patient who has lost 800ml or more of blood.
Regulation of Water Output
Output of certain amounts of water are unavoidable. Obligatory water losses include insensible water losses from the lungs and through the skin, water that accompanies undigested food residues in feces, and a minimum daily sensible water loss of 500ml in urine. Obligatory water loss in urine reflects the facts that (1) when we eat an adequate diet, our kidneys must excrete about 900 – 1200 mosm of solutes to maintain blood homeostasis, and (2) human kidneys must flush urine solutes out of the body in water.
Beyond obligatory water loss, the solute concentration and volume of urine excreted depend on fluid intake, diet, and water loss via other avenues. Normally, the kidneys begin to eliminate excess water about 30 minutes after it is ingested. This delay mainly reflects the time required for ADH release to be inhibited. Diuresis reaches a peak in 1 hour and then declines to its lowest level after 3 hours.
The body’s water volume is closely tied to a powerful water “magnet,” ionic sodium.
Disorders of Water Balance
The principal abnormalities of water balance are dehydration, hypotonic hydration, and edema, and each of these conditions offers a special set of problems to its victims.
Dehydration occurs when water loss exceeds water intake over a period of time and the body is in negative fluid balance. Dehydration is a common sequel to hemorrhage, severe burns, prolonged vomiting or diarrhea, profuse sweating, and diuretic abuse. Dehydration may also be caused by endocrine disturbances, such as diabetes mellitus or diabetes insipidus.
Early signs and symptoms of dehydration include a “cottony” or sticky oral mucosa, thirst, dry flushed skin, and decreased urine output. If prolonged, dehydration may lead to weight loss, fever, and mental confusion. Another very serious consequences of water loss from the plasma ECF compartment is inadequate blood volume to maintain normal circulation and ensuing hypovolemic shock.
In all these situations, water is lost from the ECF. This is followed by the osmotic movement of water from the cells into the ECF, which equalizes the osmolality of the extracellular and intracellular fluids even though the total fluid volume has been reduced. Though the overall effect is called dehydration, it rarely involves only a deficit of water. Most often, as water is lost electrolytes are lost as well.
When the osmolality of the ECF starts to drop (usually this reflects a deficit of Na+), several compensatory mechanisms are set into motion. Once of these is inhibition of ADH release, and as a result, excess water is quickly flushed from the body in urine. But when there is renal insufficiency or an extraordinary amount of water is drunk very quickly, a type of cellular overhydration called hypotonic hydration or water intoxication may result. In either case, the ECF is diluted – its sodium content is normal, but excess water is present.
This in turn promotes net osmosis into the tissue cells, causing them to swell as they become abnormally hydrated.
The resulting electrolyte dilution leads to severe metabolic disturbances evidenced by nausea, vomiting, muscular cramping, and cerebral edema. Water intoxication is particularly damaging to neurons. Uncorrected cerebral edema quickly leads to disorientation, convulsions, coma, and death.
Edema is an atypical accumulation of fluid in the interstitial space, leading to tissue swelling. Edema may be caused by any event that steps up the flow of fluid out of the bloodstream or hinders its return.
Factors that accelerate fluid loss from the bloodstream include increased blood pressure and / or capillary permeability. Increased blood pressure can result from incompetent venous valves, localized blood vessel blockage, congestive heart failure, hypertension, or high blood volume, for instance, during pregnancy or resulting from abnormal retention of sodium.
Increased capillary permeability is usually due to an ongoing inflammatory response. Inflammatory chemicals cause local capillaries to become very porous, allowing large amounts of exudates to form.
Edema caused by hindered fluid return to the bloodstream usually reflects an imbalance in the colloid osmotic pressures on the two sides of the capillary membranes. For example, hypoproteinemia.
Electrolytes include salts, acids, and bases, but the term electrolyte balance usually refers to the salt balance in the body. Salts provide minerals essential for neuromuscular excitability, secretory activity, membrane permeability, and many other cellular functions. Additionally, salts are important in controlling fluid movements.
Salts enter the body in foods and fluids, and small amounts are generated during metabolic activity. Salts are lost from the body in perspiration, feces, and urine.
The Central Role of Sodium in Fluid and Electrolyte Balance
Sodium holds a pivotal position in fluid and electrolyte balance and overall body homeostasis, and regulating the balance between sodium input and output is one of the most important functions of the kidneys.
Sodium is the single most abundant cation in the ECF and is the only one exerting significant osmotic pressure. Additionally, cellular plasma membranes are relatively impermeable to Na+, but some does manage to diffuse in and must be pumped out against its electrochemical gradient. These two qualities give sodium the primary role in controlling ECF volume and water distribution in the body.
It is important to understand that while the sodium content of the body may change, its concentration in the ECF normally remains stable because of immediate adjustments in water volume.
Regulation of Sodium Balance
Influence and Regulation of Aldosterone
When aldosterone concentrations are high, virtually all the remaining Na’ (actually NaCl, because Cl- is cotransported) is actively reabsorbed in the distal convoluted tubules and collecting ducts. Water follow if it can, that is, if the tubule permeability has been increased by ADH.
However, when aldosterone release is inhibited, virtually no Na’ reabsorption occurs beyond the distal tubule.
Aldosterone is produced by adrenal cortical cells. The most important trigger for aldosterone release is the rennin-angiotensin mechanism mediated by the juxtaglomerular apparatus of the renal tubules.
Cardiovascular System Baroreceptors
Blood volume is carefully monitored and regulated to maintain blood pressure and cardiovascular function. As blood volume (hence pressure) rises, baroreceptors in the heart and in the large vessels of the neck and thorax (carotid arteries ad aorta) alert the hypothalamus. Shortly after, sympathetic nervous system impulses to the kidneys decline, allowing the afferent arterioles to dilate. As the glomerular filtration rate rises, sodium and water output increase. This phenomenon, called pressure diuresis, reduces blood volume and consequently, blood pressure. In contrast, drops in systemic blood pressure lead to constriction of the afferent anterioles, which reduces filtrate formation and urinary output and increases systemic blood pressure.
Influence and Regulation of ADH
The amount of water reabsorbed in the collecting ducts of the kidneys is proportional to ADH release. When ADH levels are low, most of the water reaching the collecting ducts is simply allowed to pass through. The result in dilute urine and a reduced volume of body fluids. When ADH levels are high nearly all of the filtered water is reabsorbed and a small volume of highly concentrated urine is excreted.
Osmoreceptors of the hypothalamus sense the ECF solute concentration and trigger or inhibit ADH release from the posterior pituitary accordingly. A decrease in sodium ion concentration inhibits ADH release and allows more water to be excreted in urine, restoring normal Na’ levels in the blood. An increase in sodium levels stimulates ADH release both directly by stimulating the hypothalamic osmoreceptors and indirectly via the rennin-angiotensin mechanism. Factors that specifically trigger ADH release by reducing blood volume include prolonged fever; excessive sweating, vomiting, or diarrhea; severe blood loss; and traumatic burns.
Influence and Regulation of Atrial Natriuretic Peptide
It reduces blood pressure and blood volume by inhibiting nearly all events that promote vasoconstriction and Na+ and water retention. A trial natriuetic peptide is a hormone that is released by certain cells of the heart atria when they are stretched by the effects of elevated blood pressure.
Influence of Other Hormones
Female Sex Hormones – The estrogens are chemically similar to aldosterone and, like aldosterone, they enhance NaCl reabsorption by the renal tubules.
Progesterone seems to decrease sodium reabsorption by blocking the effect of aldosterone on the renal tubules. Thus, progesterone has a diuretic like effect and promotes sodium and water loss.
Glucocorticoids – The usual effect of glucocorticoids, such as cortisol and hydrocortisol, is to enhance tubular reabsorption of sodium. i.e. Promote edema.
Regulation of Potassium Balance
Potassium the chief intracellular cation, is required for normal neuromuscular functioning as well as for several essential metabolic activities, including protein synthesis.
Potassium excess in the ECF decrease their membrane potential, causing depolarization, which is often followed by reduced excitability. A deficit of K+ in the ECF causes hyperpolarization and nonresponsiveness. The heart is particularly sensitive to K+ levels. Both too much too little K+ (hyperkalemia and hypokalemia respectively) can disrupt electrical conduction in the heart, leading to sudden death.
Regulatory Site: The Cortical Collecting Duct
Like sodium balance, potassium balance is maintained chiefly by renal mechanisms.
The renal tubules predictably reabsorb over 90% of the filtered K+, leaving less than 10% to be lost in urine regardless of need. The responsibility for K+ balance falls chiefly on the cortical collecting ducts, and is accomplished mainly by changing the amount of potassium secreted into the filtrate.
Essentially, two factors determine the rate and extent of potassium secretion – the plasma potassium ion concentration and aldosterone levels.
Influence of Plasma Potassium Concentration
The single most important factor influencing potassium secretion is the K+ concentration in blood plasma. A high-potassium diet increases the K+ into the principal cells of the collecting duct and prompts them to secret K+ into the filtrate so that more potassium is excreted. Conversely, a low-potassium diet or accelerated K+ loss depresses its secretion by the collecting ducts.
Influence of Aldosterone
As aldosterone stimulates the principal cells to reabsorb sodium, it simultaneously enhances potassium ion secretion.
To maintain electrolyte balance there is a one-for-one exchange of Na+ and K+ in the cortical collecting ducts. For each Na+ reabsorbed, a K’ is secreted. Thus, as plasma Na+ level rise, K’ levels fall proportionately.
Adrenal cortical cells are directly sensitive to the K+ content of the ECF bathing them. When it increases even slightly, the adrenal cortex is strongly stimulated to release adlosterone, which increases potassium secretion.
Regulation of Calcium Balance
About 99% of the body’s calcium is found in bones in the form of calcium phosphate salts, which provide strength and rigidity to the skeleton. Ionic calcium in the ECF is important for normal blood clotting, cell membrane permeability, and secretory behavior. Like sodium and potassium, ionic calcium has potent effects on neuromuscular excitability. Hypocalcemia increases excitability and causes muscle tetany. Hypercalcemia is equally dangerous because it inhibits neurons and muscle cells and may cause life-threatening cardiac arrhythmias.
Calcium balance is regulated primarily by the interaction of two hormones – parathyroid hormone and calcitonin.
Influence of Parathyroid Hormone
The most important controls of Ca2+ homeostasis are exerted by parathyroid hormone (PTH), released by the tiny parathyroid glands located o the posterior aspect of the thyroid gland in the pharynx. Declining plasma levels of Ca2+ directly stimulate the parathyroid glands to release PTH, which promotes an increase in calcium levels by targeting the following organs.
- Bones – PTH activates osteoclasts (bone-digesting cells), which break down the bone matrix, resulting in the release of Ca2+ and PO42– to the blood.
- Small intestine – PTH enhances intestinal absorption of Ca2+ indirectly by stimulating the kidneys to transform vitamin D to its active form, which is a necessary cofactor for calcium absorption by the small intestine.
- Kidneys – PTH increases calcium reabsorption by the renal tubules while simultaneously decreasing phosphate ion (PO42–) reabsorption.
When calcium levels in the ECF are within normal limits (9-11mg/100ml blood) or are high, PTH secretion is inhibited. Consequently, release of calcium from bone is inhibited, larger amounts of calcium are lost in feces and urine, and more phosphate is retained.
Influence of Calcitonin
Calcitonin, a hormone produced by the parafollicular cells of the thyroid gland, is released in response to rising blood calcium levels. Calcitonin targets bone, where it encourages deposit of calcium salts and inhibits bone reabsorption.
Regulation of Magnesium Balance
Magnesium, the second most abundant intracellular cation, activates the coenzymes needed for carbohydrate and protein metabolism and plays an essential role in myocardial functioning, neurotransmission, and neuromuscular activity. Half of the magnesium in the body is in the skeleton. Most of the remainder is found intracellularly.
Control of magnesium balance is poorly understood, but a renal transport maximum for magnesium is known to exist.
Regulation of Anions
Chloride is the major anion accompanying sodium in the ECF and, like sodium, it helps maintain the osmotic pressure of the blood. When blood pH is within normal limits or is slightly alkaline, about 99% of filtered chloride ions are reabsorbed. In the PCT, they move passively and simply follow sodium ions out of the filtrate and into the peritubular capillary blood.
Most other anions, such as sulfates and nitrates, have definite transport maximums and when their concentrations in the filtrate exceed their renal thresholds, excesses still over into urine.
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