Fluid, Electrolyte, and Acid-Base Balance

Body Fluids

Body Water Content

Total body water is a function of age, body mass, and body fat.

Due to their low body fat and bone mass, infants are about 73% water.

The body water content of men is about 60%, but since women have relatively more body fat and less skeletal muscle than men, theirs is about 50%.

Body water declines throughout life, ultimately comprising about 45% of total body mass in old age.

Fluid Compartments

There are two main fluid compartments of the body: the intracellular compartment contains slightly less than two-thirds by volume; the remaining third is distributed in the extracellular fluid.

There are two subcompartments of the extracellular fluid: blood plasma and interstitial fluid.



Composition of Body Fluids

Nonelectrolytes include most organic molecules, do not dissociate in water, and carry no net electrical charge.

Electrolytes dissociate in water to ions, and include inorganic salts, acids and bases, and some proteins.

Electrolytes have greater osmotic power because they dissociate in water and contribute at least two particles to solution.

The major cation in extracellular fluids is sodium, and the major anion is chloride; in intracellular fluid the major cation is potassium, and the major anion is phosphate.

Electrolytes are the most abundant solutes in body fluids, but proteins and some nonelectrolytes account for 60­–97% of dissolved solutes.

Fluid Movement Among Compartments

Anything that changes solute concentration in any compartment leads to net water flows.

Nearly protein-free plasma is forced out of the blood by hydrostatic pressure, and almost completely reabsorbed due to colloid osmotic (oncotic) pressure of plasma proteins.

Movement of water between the interstitial fluid and intracellular fluid involves substantial two-way osmotic flow that is equal in both directions.

Ion fluxes between the interstitial and intracellular compartments are restricted; but movement of nutrients, respiratory gases, and wastes typically occur in one direction. 

Water Balance and ECF Osmolality

For the body to remain properly hydrated, water intake must equal water output.

Most water enters the body through ingested liquids and food, but is also produced by cellular metabolism.

Water output is due to evaporative loss from lungs and skin (insensible water loss), sweating, defecation, and urination.

Regulation of Water Intake

The thirst mechanism is triggered by a decrease in plasma osmolarity, which results in a dry mouth and excites the hypothalamic thirst center.

  Thirst is quenched as the mucosa of the mouth is moistened, and continues with distention of the stomach and intestines, resulting in inhibition of the hypothalamic thirst center.

Regulation of Water Output

Drinking is necessary since there is obligatory water loss due to the insensible water losses.

Beyond obligatory water losses, solute concentration and volume of urine depend on fluid intake.

Influence of ADH

The amount of water reabsorbed in the renal collecting ducts is proportional to ADH release.

When ADH levels are low, most water in the collecting ducts is not reabsorbed, resulting in large quantities of dilute urine.

When ADH levels are high, filtered water is reabsorbed, resulting in a lower volume of concentrated urine.

ADH secretion is promoted or inhibited by the hypothalamus in response to changes in solute concentration of extracellular fluid, large changes in blood volume or pressure, or vascular baroreceptors.

Disorders of Water Balance

Dehydration occurs when water output exceeds water intake, and may lead to weight loss, fever, mental confusion, or hypovolemic shock.

Hypotonic hydration is a result of renal insufficiency, or intake of an excessive amount of water very quickly.

Edema is the accumulation of fluid in the interstitial space, which may impair tissue function.

Electrolyte Balance

The Central Role of Sodium in Fluid and Electrolyte Balance

Sodium is the most important cation to regulation of fluid and electrolyte balance in the body due to its abundance and osmotic pressure.

Since all body fluids are in chemical equilibrium, any change in sodium levels causes a compensatory shift in water, affecting plasma volume, blood pressure, and intracellular and interstitial fluid volumes.

Sodium Concentration vs. Sodium Content

Regulation of Sodium Balance

Influence of Aldosterone and Angiotensin II

When aldosterone secretion is high, nearly all the filtered sodium is reabsorbed in the distal convoluted tubule and the collecting duct.

The most important trigger for the release of aldosterone is the renin-angiotensin mechanism, initiated in response to sympathetic stimulation, decrease in filtrate osmolality, or decreased blood pressure.


Influence of Atrial Natriuretic Peptide (ANP)

Atrial natriuretic peptide reduces blood pressure and blood volume by inhibiting release of ADH, renin, and aldosterone, and directly causing vasodilation.

Influence of Other Hormones

Estrogens are chemically similar to aldosterone, and enhance reabsorption of salt by the renal tubules.

Progesterone promotes Na+ and water loss, apparently by antagonizing the effects of aldosterone.

Glucocorticoids enhance tubular reabsorption of Na+, but also increase the glomerular filtration rate. At high levels reabsorption dominates, which promotes edema.

Cardiovascular Baroceptors

Cardiovascular baroreceptors monitor blood volume so that blood pressure remains stable.

High blood volume/blood pressure causes sympathetic stimuli to the kidneys to decline and the afferent arteriles to dilate. The glomerlular filtration rate rises, sodium and water output increase, blood volume and blood pressure decrease.

Low blood pressure causes reflex constriction of systemic arterioles (including afferent arterioles), reducing filtrate formation and urinary output and leading to an increase in systemic blood pressure.



Regulation of Potassium Balance

Potassium is critical to the maintenance of the membrane potential of neurons and muscle cells, and is a buffer that compensates for shifts of hydrogen ions in or out of the cell.

Potassium balance is chiefly regulated by renal mechanisms, which control the amount of potassium secreted into the filtrate.

Blood plasma levels of potassium are the most important factor regulating potassium secretion.

Aldosterone influences potassium secretion, since potassium secretion is simultaneously enhanced when sodium reabsorption increases.

Regulation of Calcium and Phosphate Balance

Calcium ion levels are closely regulated by parathyroid hormone and calcitonin; about 98% is reabsorbed.

Parathyroid hormone is released when blood calcium levels decline, and targets the bones, small intestine, and kidneys.

Calcitonin is an antagonist to parathyroid hormone, and is released when blood calcium rises, targeting bone.

Regulation of Anions

Chloride is the major anion reabsorbed with sodium, and helps maintain the osmotic pressure of the blood.

Acid-Base Balance

Because of the abundance of hydrogen bonds in the body’s functional proteins, they are strongly influenced by hydrogen ion concentration.

When arterial blood pH rises above 7.45, the body is in alkalosis; when arterial pH falls below 7.35, the body is in acidosis.

Most hydrogen ions originate as metabolic by-products, although they can also enter the body via ingested foods.

Chemical Buffer Systems

A chemical buffer is a system of one or two molecules that acts to resist changes in pH by binding H+ when the pH drops, or releasing H+ when the pH rises.

The bicarbonate buffer system is the main buffer of the extracellular fluid, and consists of carbonic acid and its salt, sodium bicarbonate.

When a strong acid is added to the solution, carbonic acid is mostly unchanged, but bicarbonate ions of the salt bind excess H+, forming more carbonic acid. 

When a strong base is added to solution, the sodium bicarbonate remains relatively unaffected, but carbonic acid dissociates further, donating more H+ to bind the excess hydroxide.

Bicarbonate concentration of the extracellular fluid is closely regulated by the kidneys, and plasma bicarbonate concentrations are controlled by the respiratory system.

The phosphate buffer system operates in the urine and intracellular fluid similar to the bicarbonate buffer system: sodium dihydrogen phosphate (NaH2PO4) is its weak acid, and monohydrogen phosphate (Na2HPO4) is its weak base.

The protein buffer system consists of organic acids containing carboxyl groups that dissociate to release H+ when the pH begins to rise, or bind excess H+ when the pH declines.

R-COOH, containing the carboxylic acid group, donates H+ to lower pH and free amino groups, NH2-R, accept H+ to raise pH

Respiratory Regulation of H+

Carbon dioxide from cellular metabolism enters erythrocytes and is converted to bicarbonate ions for transport in the plasma.

When hypercapnia occurs, blood pH drops, activating medullary respiratory centers, resulting in increased rate and depth of breathing and increased unloading of CO2 in the lungs.

When blood pH rises, the respiratory center is depressed, allowing CO2 to accumulate in the blood, lowering pH.

Renal Mechanisms of Acid-Base Balance

Only the kidneys can rid the body of acids generated by cellular metabolism (nonvolatile or fixed acids), while also regulating blood levels of alkaline substances and renewing chemical buffer components.

Bicarbonate ions can be conserved from filtrate when depleted, and their reabsorption is dependent on H+ secretion.

Conservation of Bicarbonate Ions


Type A intercalated cells of the renal tubules can synthesize new bicarbonate ions while excreting more hydrogen ions.

Synthesis of New Bicarbonate/Excretion of Buffered H+


Ammonium ions are weak acids that are excreted and lost in urine, replenishing the alkaline reserve of the blood.

NH4+ Excretion


When the body is in alkalosis, type B intercalated cells excrete bicarbonate, and reclaim hydrogen ions.

Abnormalities of Acid-Base Balance

Respiratory acidosis is characterized by falling blood pH and rising PCO2, which can result from shallow breathing or some respiratory diseases.

Respiratory alkalosis results when carbon dioxide is eliminated from the body faster than it is produced, such as during hyperventilation.

Metabolic acidosis is characterized by low blood pH and bicarbonate levels, and is due to excessive loss of bicarbonate ions, or ingestion of too much alcohol.

Metabolic alkalosis is indicated by rising blood pH and bicarbonate levels, and is the result of vomiting or excessive base intake.

Respiratory Compensation

Respiratory rate and depth increases during metabolic acidosis.

Blood pH is low (< 7.35) and the HCO3- level is below 22 mEq/L. Blowing off more CO2 causes the PCO2 to drop below 35 mm Hg.

Respiratory rate and depth decreases during metabolic alkalosis.

This allows CO2 to accumulate in the blood. Evidence of respiratory compensation for metabolic alkalosis includes pH > 7.45, HCO3- levels over 26 mEq/L, and a PCO2 > 45 mm Hg.

Renal Compensation

In renal compensation for respiratory acidosis, blood PCO2 and HCO3- concentrations are high; in respiratory alkalosis, blood pH is high, but PCO2 is low.


Developmental Aspects of Fluid, Electrolyte, and Acid-Base Balance

An embryo and young fetus are more than 90% water, but as solids accumulate, the percentage declines to about 70–80% at birth.

Distribution of body water begins to change at 2 months of age, and takes on adult distribution by the time a child is 2 years of age.

At puberty, sex differences in body water content appear as males develop more skeletal muscle.

During infancy, problems with fluid, electrolyte, and acid-base balance are common, due to large-scale changes in PCO2.

Infant lungs have low residual volumes.

Infants have a high rate of fluid intake and output, putting them at risk for excessive fluid shifts.

Infants have a high metabolic rate (and generate more metabolic wastes and acids) and ineffective buffer systems, which favors acidosis.

Infants have a large surface area to volume ratio, causing them to have a high rate of insensible water loss.

Infants have inefficient kidneys, making it harder to rid the body of acids.

In old age, body water loss is primarily from the intracellular compartment, due to decline in muscle mass, and increase in adipose tissue.

Increased insensitivity to thirst cues makes the elderly vulnerable to dehydration, and electrolyte or acid-base imbalances.