Physiology, Body Fluids

Article Author:
Joshua Brinkman
Article Editor:
Sandeep Sharma
3/9/2019 10:01:29 PM
PubMed Link:
Physiology, Body Fluids


Human beings are creatures that are primarily composed of water. It is the essence of life and the aqueous base solution in which all essential biochemical processes occur that produce life. Humans are approximately 75% water by mass as infants and 50% to 60% water by mass as adults. Furthermore, fluid is always in flux through a variety of regulatory mechanisms to maintain appropriate concentrations throughout the various compartments of the body. Fluid is largely regulated through passive diffusion following the concentration gradients of osmotically active solutes; however, hydrostatic pressures can influence fluid movement between spaces.[1]


The distribution of fluid throughout the body can be broken down into 2 general categories: intracellular fluid and extracellular fluid.  Intracellular fluid is approximately 40% of the total body weight. It is the total space within cells primarily defined as the cytoplasm of cells.  In general, intracellular fluids are stable and do not readily adjust rapidly to changes. This space is where much of chemical reactions occur, as such, it is important to maintain an appropriate osmolality. The extracellular fluid comprises approximately 20% of total body weight and further subcategorizes as plasma at approximately 5% of body weight and interstitial space which is approximately 12% of body weight. Additional fluid spaces are possible in pathological scenarios and are categorized based on location and etiology as a transudate or exudate.

The exact chemical composition of body fluid is highly variable. This is dependent on which portion of the body, as well as which organ of the body, contains the fluid. Extracellular fluid and interstitial fluid are similar in composition. Extracellular spaces contain high concentrations of sodium, chloride, bicarbonate, and proteins but are relatively lower in potassium, magnesium, and phosphates. Interstitial fluids physiologically tend to have a low concentration of proteins. Intracellular fluids tend to be an inverse with high levels of phosphate, magnesium, potassium, and proteins but lower sodium, chloride, and bicarbonate.[2][3][4]


Fluid moves throughout cellular environments in the body by passively crossing semipermeable membranes. Osmolality is defined as the number of particles per liter of fluid. Physiologic blood plasma osmolarity is approximately 286 mOsmoles/L. Less than this is hypoosmotic, and greater is hyperosmotic. Cellular osmotic concentration gradients are maintained largely through the active pumping efforts of cellular transmembrane ionic transport proteins.  However, rapid changes in fluid without changes in ionic components causes dilation or concentration of those components. Blood plasma osmotic gradients are maintained through the absorption of solutes from the gastrointestinal tract or secretion into the gastrointestinal tract or urine. In addition to ionic components, osmolality is partially composed of proteins such as albumin in the serum. Another important osmotically active component to consider is glucose. Fluid will move towards hyper-osmolar compartments and away from hypo-osmolar compartments. All body fluids should have an ionic net electoral charge close to zero indicating a balance of cations and anions. Ionic components will diffuse through fluids selectively depending on the presence of permeable membranes. If a membrane is non-permeable to an ion, this creates a gradient of relatively higher concentration osmolarity. Solute gradients can be physiologically created by membrane pumping proteins, which expend energy in the form of ATP to move components from areas of low concentration into higher concentrations against its diffusion gradient. These processes create a cellular environment to osmotically “pull” water into fluid compartments. In addition to the osmotic pull of fluids, fluid movement within the body is reliant on created and maintained hydrostatic pressures. This is best utilized in the movement of fluid from plasma in the extracellular blood space into the interstitial spaces of tissue across the capillary membrane. Hydrostatic pressure is the “push” factor on fluid movement where increased pressures force fluid out of a space.  The combined “push” of hydrostatic forces and “pull” of osmotic forces create a net movement of fluid. This is mathematically explained using the Starling equation:

  • Jv = Kfc ([Pc - Pi] - n [Op-Oi])

Where Jv is the net rate of capillary fluid movement, Kfc is a capillary filtration fluid coefficient, Pc is capillary hydrostatic pressure, Pi is interstitial hydrostatic pressure, n is the osmotic reflection coefficient, Op is plasma oncotic pressure, and Oi interstitial oncotic pressure.[4]

Clinical Significance

A variety of pathological conditions induces abnormalities in fluid balance. Fluid balance abnormalities are either an overload of fluid or a decrease in effective fluid. Fluid overload is clinically known as edema. Edema occurs most commonly in soft tissues of the extremities; however, it is possible to occur in any tissue. Fluid load decreased are commonly referred to as dehydration.

Edema manifests in the soft tissues as swelling of the limbs and face with a subsequent increase in size and tightness of the skin. Peripheral edema is reducible by increasing the pressure in the interstitial space and is measured by pressing a finger into the tissue which will create a formed dimple in the edematous skin temporarily. Likewise, compression stockings can reduce peripheral edema while worn by increasing interstitial hydrostatic pressure, forcing fluid back into the capillaries.

Pulmonary edema may occur. Where excess fluid swells into interstitial tissues of the lung. Symptoms include shortness of breath and chest pain. A physical exam will include orthopnea where respiration is impaired while lying flat as this distributes the excess fluid across the entire lung essentially flooding a patient’s lungs in their fluid. Pulmonary edema is life threatening as it compromises gas exchange in the lungs and can quickly decompensate. Pulmonary edema is associated with cardiac failure and renal failure. Classically, cardiac failure causes pulmonary edema through decreased pumping efficiency and capacity of the left atria and left ventricle. This creates a back pressure in the pulmonary veins increasing pressure in the vessel. Subsequently, hydrostatic pressures in the pulmonary capillaries are increased, “pushing” fluid into the interstitial lung space following the Starling equation. Renal failure causes edema through a failure to remove fluids and osmotic components from the body. The net result is increased osmotic pull into tissues and increased hydrostatic push out of capillaries.[5]

Liver disease is also capable of inducing edema. This is due to a failure to produce osmotically active proteins. Specifically, a failure to produce albumin. Albumin is found physiologically primarily in the plasma of the extracellular blood. It is not found in the interstitial space typically. As such, a decrease in body albumen directly decreases the “pull” osmotic pressure into the capillaries. According to Starling forces, this results in the fluid to move into the interstitial spaces.[6]

Additionally, fluid overload can be iatrogenically induced by excessive fluid replacement via intravenous (IV) fluid replacement.

Edema is treated for symptomatic relief using a variety of medications including diuretics to remove fluid from the body via the renal system. In cases of low plasma albumin, albumin may be supplemented. Lifestyle changes can include reducing sodium intake, fluid intake, and wearing compression stockings. However, targeting the underlying pathology to improve cardiac function, correct hepatic injury, or renal failure offers better results than simply removing fluid, replacing osmotic components, or other lifestyle symptomatic improvement measures.

Dehydration is largely due to failure to intake enough water to meet the body’s metabolic needs. The average adult has an obligatory intake requirement of 1600 mL per day. This value increases depending on activity and metabolism. Primary sources of normal loss include urine, sweat through the skin, respiratory losses, and stool losses. Pathological causes include diarrhea, vomitus, infection, and increased urination secondary to SIADH, diabetes mellitus, and diabetes insipidus. Dehydration manifests clinically as decreased urine output, dizziness, fatigue, tachycardia, increased skin turgidity, and fatigue or confusion in severe cases. Whenever possible, oral fluid replacement should be attempted. In more urgent situations, IV fluid replenishment should be based on bolus supplementation of the deficit of fluids and a maintenance replenishment of obligatory intake requirements. The fluid deficit can be calculated when the pre-dehydration weight and post-dehydration weight are known. The equation in males is:

  • Deficit = 0.6 X weight in kilograms X ((Current Na/140)-1)

In females, the equation is:

  • Deficit = 0.5 X weight in kilograms X ((Current Na/140)-1)

This equation is highly useful in determining initial fluid deficit. However, it has limitations in accuracy as great as a multiple of 40%. In pediatric patients, the fluid deficit is directly correlated to body weight loss from pre-illness compared to post-illness. One liter of free water weighs 1 mg. Therefore, a 10-kg pre-illness child that weighs 9 kg in illness has a fluid deficit of 1L.  In emergency scenarios, a bolus volume of 30 mL/kg is used to replace the loss. In obese patients, however, this leads to over repletion of free water. Therefore, it is recommended to base bolus fluid resuscitation on adjusted ideal body weight (AIBW) in obese patients. This is derived from the ideal body weight (IBW) and the actual body weight (ABW).

  • AIBW = IBW + 0.4 (ABW - IBW)

Where ideal body weight is calculated as:

  • Males: IBW = 50 kg + 2.3 kg for each inch over 5 feetFemales: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet

Maintenance fluid is determined using a formula based on weight also.  Fluid should be replaced at a rate of:

  • 4 mL / Kg / hr for Kg 1-10 + 2mL / Kg / hr for kg 10-20 + 1 mL / kg / hr above 20 kg

In other words, if a patient weighs 55 kilograms the will require:

  • 40 mL/hr + 20 mL/hr + 35 mL = 95 mL/hr of free water

IV fluid replacement options include normal saline (0.9% NaCl), one-half normal saline (0.45% NaCl), Dextrose 5% in either normal saline or one-half normal saline, and lactated Ringer's solution. The choice of replacement fluids is patient scenario-specific and dependent on the electrolyte status of laboratory evaluation.[7]

Burn patients require specialized increases in fluid replacement secondary to the immense loss of free water through their wounds. The needed fluid resuscitation is calculated using Parkland’s formula and Brooke’s formula. Modified Brooke formula is 2 mL times body surface areas burned times weight in kg equals fluid resuscitation needed.[8]

The Parkland formula is 2 mL times body surface areas burned times weight in kg equals fluid resuscitation needed.

Both formulas estimate the first 24-hour fluid requirements from the time of the burn, with half the amount to be given in the first 8 hours.  While both formulas give widely different values, they give equivalent outcomes. Final fluid needs should be based on urine output rate.

Diabetic ketoacidosis is an illness that results in a failure of the body to utilize glucose for energy production. Glucose is an osmotically active substance that is excreted in the urine at high concentrations. This leads to subsequent extreme fluid loss through the urine and dehydration. This necessitates large volume resuscitation of 6 to 9 L of normal saline on average.

Hyperosmolar hyperglycemic non-ketotic acidosis is a similar illness to diabetic ketoacidosis, except is lacks ketone production. It requires a similar fluid resuscitation.

In hypernatremic patients who have a fluid replacement with rapid subsequent correction of hypernatremia are at increased risk for developing cerebral edema. Cerebral edema is an illness where intracellular and extracellular fluid loads increase causing increased pressure within the brain space. This leads to neurological deficits and ultimately death. This illness can be avoided by slowly infusing fluids such that sodium levels reduce at an initial rate of 2 to 3 mEq/L per hour for a maximum total change of 12 mEq/L per day until sodium is in a normal range.

Conversely, rapid correction of hyponatremia may lead to cerebral pontine myelinolysis syndrome. This is also known as “locked-in syndrome” characterized by paralysis, dysphagia, and dysarthria. This occurs when fluid rapidly shifts into the myelin sheath of the nervous system and causes lysis of the cellular tissue. This can be avoided by increasing the serum sodium level by approximately 1 to 2 mEq/L per hour until the neurologic symptoms of hyponatremia subside or until plasma sodium concentration is over 120 mEq/L.

Crystalloid fluid resuscitation offers complications as they alter the ionic load of the serum. Specifically, normal saline replacement may lead to non-gap hyperchloremic metabolic acidosis. One-half normal saline if not monitored closely may dilute ionic components leading to hyponatremia or hypokalemia less often. Abdominal compartment syndrome in septic shock patients is possibly secondary to fluid overload with the subsequent leak of fluid from capillaries into extravascular spaces.

Colloid fluid resuscitation has its risks as well. The 2 major colloids used are albumen and hydroxyethyl starch. In the SAFE trial which compared 4% albumin fluid with 0.9% normal saline, it was determined that outcomes are equivalent. However, in specific cases involving neurological injury, 4% albumin has an increased mortality rate compared to normal saline. As such, albumin should be avoided in this situation. Hydroxyethyl starch was studied in comparison and found to carry an increased risk of death or end-stage renal failure when compared to lactated Ringer's solution when used in sepsis patients.

Diuretics causing are closely associated with inducing contraction metabolic alkalosis.[9][10][11]


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