Body Fluids – Physiology, Mechanism, Functions

Water Content in the Body

A significant percentage of the human body is water, which includes intracellular and extracellular fluids.

Water Content

In physiology, body water is the water content of the human body. It makes up a significant percentage of the total composition of a body. Water is a necessary component to support life for many reasons. All cells in the human body are made mostly of water content in their cytoplasm.

Water molecule: A 3-dimensional model of hydrogen bonds (labeled 1) between molecules of water.

Water also provides a fluid environment for extracellular communication and molecular transport throughout the body. Water itself is also a key component of biochemical reactions involved in physiology, such as hydrolysis. Many organ systems depend on the physical properties of water, such as the surface tension of water in the alveoli of the lungs.

Overall Water Content

The total amount of water in a human of average weight (70 kilograms) is approximately 40 liters, averaging 57 percent of his total body weight. In a newborn infant, this may be as high as 79 percent of the body weight, but it progressively decreases from birth to old age, with most of the decrease occurring during the first 10 years of life.

Also, obesity decreases the percentage of water in the body, sometimes to as low as 45 percent. The water in the body is distributed among various fluid compartments that are interspersed in the various cavities of the body through different tissue types. In diseased states where body water is affected, the fluid compartments that have changed can give clues to the nature of the problem.

Water Content Regulation and Measurement

Body water is regulated largely by the renal and neuroendocrine systems. Water content regulation is one of the most important parts of homeostasis due to its influence on blood pressure and cardiac output. Much of this regulation is mediated by hormones, including anti-diuretic hormone (ADH), renin, angiotensin II, aldosterone, and atrial natriuretic peptide (ANP).

These hormones act as messengers between the kidneys and the hypothalamus; however, the lungs and heart are also involved in the secretion of some of these hormones, such as an angiotensin-converting enzyme (ACE) and ANP respectively.

There are many clinical methods to determine body water. One way to get an uncertain estimate is by calculation based on body weight and urine output. Another way to measure body water is through dilution and equilibration using mass spectrometry, which measures the abundance of water in breath samples from an individual.

In bioelectrical impedance analysis, a person’s hydration level is calculated from high-precision measurements of the opposition to the flow of an electric current through body tissues. Since water conducts electricity, a lower hydration level will cause a greater amount of resistance to electrical flow through the body.

Fluid Compartments

The major body-fluid compartments include intracellular fluid and extracellular fluid (plasma, interstitial fluid, and transcellular fluid).

Fluid Compartments

The fluids of the various tissues of the human body are divided into fluid compartments. Fluid compartments are generally used to compare the position and characteristics of fluid in relation to the fluid within other compartments.

While fluid compartments may share some characteristics with the divisions defined by the anatomical compartments of the body, these terms are not one in the same. Fluid compartments are defined by their position relative to the cellular membrane of the cells that make up the body’s tissues.

Intracellular Fluid

The intracellular fluid of the cytosol or intracellular fluid (or cytoplasm ) is the fluid found inside cells. It is separated into compartments by membranes that encircle the various organelles of the cell. For example, the mitochondrial matrix separates the mitochondrion into compartments.

The contents of a eukaryotic cell within the cell membrane, excluding the cell nucleus and other membrane-bound organelles (e.g., mitochondria, plastides, lumen of endoplasmic reticulum, etc.), is referred to as the cytoplasm.

The cytosol is a complex mixture of substances dissolved in water. Although water forms the large majority of the cytosol, it mainly functions as a fluid medium for intracellular signaling (signal transduction ) within the cell, and plays a role in determining cell size and shape.

The concentrations of ions, such as sodium and potassium, are generally lower in the cytosol compared to the extracellular fluid; these differences in ion levels are important in processes such as osmoregulation and signal transduction. The cytosol also contains large amounts of macromolecules that can alter how molecules behave, through macromolecular crowding.

Extracellular Fluid

Extracellular fluid (ECF) or extracellular fluid volume (ECFV) usually denotes all the body fluid that is outside of the cells. The extracellular fluid can be divided into two major subcompartments: interstitial fluid and blood plasma.

The extracellular fluid also includes the transcellular fluid; this makes up only about 2.5% of the ECF. In humans, the normal glucose concentration of extracellular fluid that is regulated by homeostasis is approximately 5 mm. The pH of extracellular fluid is tightly regulated by buffers and maintained around 7.4.

The volume of ECF is typically 15L (of which 12L is interstitial fluid and 3L is plasma). The ECF contains extracellular matrices (ECMs) that act as fluids of suspension for cells and molecules inside the ECF.

Blood Plasma

Blood plasma is the straw-colored/pale-yellow, liquid component of blood that normally holds the blood cells in whole blood in suspension, making it a type of ECM for blood cells and a diverse group of molecules. It makes up about 55% of total blood volume.

It is the intravascular fluid part of the extracellular fluid. It is mostly water (93% by volume) and contains dissolved proteins (the major proteins are fibrinogens, globulins, and albumins), glucose, clotting factors, mineral ions (Na+, Ca++, Mg++, HCO3- Cl-, etc.), hormones, and carbon dioxide (plasma is the main medium for excretory product transportation). It plays a vital role in intravascular osmotic effects that keep electrolyte levels balanced and protects the body from infection and other blood disorders.

Interstitial Fluid

Interstitial fluid (or tissue fluid) is a solution that bathes and surrounds the cells of multicellular animals. The interstitial fluid is found in the interstitial spaces, also known as the tissue spaces.

On average, a person has about 11 liters (2.4 imperial gallons or about 2.9 U.S. gal) of interstitial fluid that provide the cells of the body with nutrients and a means of waste removal. The majority of the interstitial space functions as an ECM, a fluid space consisting of cell-excreted molecules that lies between the basement membranes of the interstitial spaces. The interstitial ECM contains a great deal of connective tissue and proteins (such as collagen) that are involved in blood clotting and wound healing.

Transcellular Fluid

Transcellular fluid is the portion of total body water contained within the epithelial-lined spaces. It is the smallest component of extracellular fluid, which also includes interstitial fluid and plasma. It is often not calculated as a fraction of the extracellular fluid, but it is about 2.5% of the total body water.

Examples of this fluid are cerebrospinal fluid, ocular fluid, joint fluid, and the pleaural cavity that contains fluid that is only found in their respective epithelium-lined spaces.

The function of the transcellular fluid is mainly lubrication of these cavities, and sometimes electrolyte transport.

Body Fluid Composition

The composition of tissue fluid depends upon the exchanges between the cells in the biological tissue and the blood.

Body Fluid Composition

The composition of tissue fluid depends upon the exchanges between the cells in the biological tissue and the blood. This means that fluid composition varies between body compartments.

Intracellular Fluid Composition

The cytosol or intracellular fluid consists mostly of water, dissolved ions, small molecules, and large, water-soluble molecules (such as proteins). This mixture of small molecules is extraordinarily complex, as the variety of enzymes that are involved in cellular metabolism is immense.

Ions: Ions in solution.

Movement of Fluid Among Compartments

How fluid moves through compartments depends on several variables described by Starling’s equation.

Fluid Movement

Extracellular fluid is separated among the various compartments of the body by membranes. These membranes are hydrophobic and repel water; however, there a few ways that fluids can move between body compartments. There are small gaps in membranes, such as the tight junctions, that allow fluids and some of their contents to pass through membranes by way of pressure gradients.

Formation of Interstitial Fluid

Hydrostatic pressure is generated by the contractions of the heart during systole. It pushes water out of the small tight junctions in the capillaries. The water potential is created due to the ability of the small solutes to pass through the walls of capillaries.

This buildup of solutes induces osmosis. The water passes from a high concentration (of water) outside of the vessels to a low concentration inside of the vessels, in an attempt to reach an equilibrium. The osmotic pressure drives water back into the vessels. Because the blood in the capillaries is constantly flowing, equilibrium is never reached.

The balance between the two forces differs at different points on the capillaries. At the arterial end of a vessel, the hydrostatic pressure is greater than the osmotic pressure, so the net movement favors water and other solutes being passed into the tissue fluid.

At the venous end, the osmotic pressure is greater, so the net movement favors substances being passed back into the capillary. This difference is created by the direction of the flow of blood and the imbalance in solutes created by the net movement of water that favors the tissue fluid.

Removal of Interstitial Fluid

The lymphatic system plays a part in the transport of tissue fluid by preventing the buildup of tissue fluid that surrounds the cells in the tissue. Tissue fluid passes into the surrounding lymph vessels and eventually rejoins the blood.

Sometimes the removal of tissue fluid does not function correctly and there is a buildup, which is called edema. Edema is responsible for the swelling that occurs during inflammation, and in certain diseases where the lymphatic drainage pathways are obstructed.

Starling Equation

Capillary dynamics: Oncotic pressure exerted by the proteins in blood plasma tends to pull water into the circulatory system.

This is a diagram of the Starling model. Note how the concentration of interstitial solutes increases proportionally to the distance from the arteriole.

According to Starling’s equation, the movement of fluid depends on six variables:

• Capillary hydrostatic pressure (Pc)
• Interstitial hydrostatic pressure (Pi)
• Capillary oncotic pressure (πz)
• Interstitial oncotic pressure (πi)
• Filtration coefficient (Kf)
• Reflection coefficient (σ)

The Starling Equation is mathematically described as Flux=Kf[(Pc-Pi)-σ (πz-πi)

Clinical Significance

A variety of pathological conditions induce 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. Decreases in fluid load are commonly referred to as dehydration.

Edema manifests as swelling in the soft tissues 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, creating a dimple in the edematous skin temporarily. Likewise, wearing compression stockings can reduce peripheral edema by increasing interstitial hydrostatic pressure, forcing fluid back into the capillaries.

Pulmonary edema is a condition when excess fluid swells into interstitial tissues of the lung. Symptoms include shortness of breath and chest pain. Orthopnea, or impaired respiration while lying flat, may also be present as the excess fluid is distributed across the entire lung. Pulmonary edema is life-threatening as it compromises gas exchange in the lungs and conditions 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 atrium and left ventricle. This creates a back pressure in the pulmonary veins, increasing pressure in the vessels. 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 typically not found in the interstitial space. As such, a decrease in body albumen directly decreases the “pull” of osmotic pressure into the capillaries. According to Starling forces, this results in the fluid moving into the interstitial spaces.[rx]

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

Edema is treated for symptomatic relief using a variety of medications including diuretics to remove fluid from the body via the renal system. Diuretics are closely associated with inducing contraction metabolic alkalosis. Albumin may be supplemented in cases of low plasma albumin. Lifestyle changes can include reducing sodium intake, restricting fluid intake, and wearing compression stockings. However, targeting the underlying pathology to improve cardiac, hepatic, or renal function offers better results than symptomatic treatment by simply removing fluid, replacing osmotic components, or other lifestyle changes.

Dehydration is largely due to inadequate water intake 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 fluid loss include urine, sweat, respiration, and stool. Pathological causes include diarrhea, vomiting, infection, and increased urination secondary to SIADH, diabetes mellitus, or 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 [1-(140/measured Na)]

In females, the equation is:

• Deficit = 0.5 X weight in kilograms X [1-(140/measured Na)]

This equation is highly useful in determining the initial fluid deficit. However, it has limitations in accuracy and can underestimate total fluid loss by more than 40%. While the above equation can be useful in initial fluid resuscitation, a more accurate approach uses plasma osmolarity instead of sodium, using 290 mmol/kg as the standard value. In pediatric patients, the fluid deficit is directly correlated to bodyweight loss from pre-illness compared to post-illness. One liter of free water weighs 1 kg. Therefore, a 10-kg pre-illness child that weighs 9 kg in illness has a fluid deficit of 1 L. 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 feet females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet

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

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

In other words, a patient who weighs 55 kilograms would 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.[rx]

Burn patients require specialized increases in fluid replacement secondary to the immense loss of free water through their wounds. The needed fluid resuscitation in adults is calculated using Parkland’s formula and Brooke’s formula. The modified Brooke formula is:

• 2 mL/kg/% body surface area burned

The modified Parkland formula is:

• 4 mL/kg/% body surface area burned

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 the urine output rate.[rx]

Diabetic ketoacidosis is a complication of diabetes mellitus that results when the body fails to utilize glucose for energy production. Glucose is an osmotically active substance that is excreted in the urine at high concentrations. This leads to 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 it lacks ketone production. It requires a similar fluid resuscitation.

In hypernatremic patients who undergo fluid replacement with rapid subsequent correction of hypernatremia are at an increased risk for developing cerebral edema. This develops due to increased intracellular and extracellular fluid loads and increased pressure within the brain space. This leads to neurological deficits and ultimately death. This condition can be avoided by slowly infusing fluids such that sodium levels are reduced 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 central pontine myelinolysis syndrome. Brain cells adapt to chronic states of hyponatremia by shifting organic osmoles, such as amino acids, from the intracellular compartment to the extracellular compartment. This allows the cells to maintain their original volume. When hyponatremia is rapidly corrected, brain cells shrink and the tight junctions of the blood-brain barrier are disrupted, leading to cell damage and demyelination of neurons.[rx] This can lead to what is known as “locked-in syndrome,” which is characterized by paralysis, dysphagia, and dysarthria. The serum sodium should be increased 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, less often, hypokalemia. 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 two 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.[rx][rx][rx]

References