Fluid balance is a carefully regulated system with many mechanisms to monitor and modify the absorption and secretion of water. Water is in constant motion between compartments that make up the body. When the body senses a drop in the effective circulating volume it stimulates a response to restore blood pressure and retain fluids. When there is too much fluid the body increases secretion and excretion of the excess.

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Drinking water

Image: “A characteristic delta wave seen in a patient with WPW. Note short PR interval.” by Antonio Calero. License: CC BY-SA 2.0

Body Fluid Distribution

Distribution of Water in the Human Body

Image: “Distribution of Water in the Human Body” by OpenStax College. License: CC BY 3.0

The average human body is composed of 35–40 % tissue and bone by weight and 60–65 % water. We call this water total body water and it is distributed into three compartments throughout the body. 2/3 of the total body water is intracellular and and found in the cytoplasm and nucleus of all types of cells: red blood cells, white blood cells, epithelial cells, fat cells, etc.

The other 1/3 of total body water is in the extracellular space. 1/3 of the extracellular water is found intravascularly, this is the plasma in the blood vessels, and 2/3 in the interstitium, the space between cells that makes up tissue. So all of the plasma that maintains tissue perfusion and blood pressure only equals a paltry 1/9 of the total body water.

Intracellular Water

2/3 of total body water or 6/9 of total body water

Interstitial Water

2/3 of extracellular water or 2/9 of total body water

Intravascular Fluid

1/3 of extracellular water or 1/9 of total body water

Extracellular Water

1/3 of total body water

Water is constantly moving between compartments via osmosis and always down its concentration gradient. Increasing the intracellular solute concentration will result in a fluid shift from the extracellular space (both interstitial water and intravascular fluid).

As total body water is gained or lost it always comes from the intravascular space first. For instance, if a person drinks hypotonic or pure water, it dilutes the intravascular fluid, resulting in a fluid shift to the interstitial space and then the intracellular space. If a person drinks hypertonic salt water, it will increase the solute concentration of the intravascular space and fluid will shift from the interstitial space into the intravascular space followed by a fluid shift from the intracellular space into the interstitial space until the body is once again in equilibrium.

Fluid Compartments in the Human Body

Image: “Fluid Compartments in the Human Body” by PhilSchatz. License: CC BY 4.0

Intake and Output

Normal Prolonged, heavy exercise
Fluids ingested 2100 ?
From metabolism 200 ?
Total intake 2300 ?
Insensible: skin 350 350
Insensible: lungs 350 650
Sweat 100 5000
Feces 100 100
Urine 1400 500
Total output 2300 6600

Water addition

Water is added to the body in a variety of ways. Under normal conditions water is consumed as a free liquid or bound in solid food. About 22 % of consumed water comes from food consumption in a typical western diet.

Normally, as much as 2 L of dietary fluid can be consumed in any one day. As it passes through the gastrointestinal (GI) system water and food is mixed with 6–7 L of digestive secretions consisting of saliva, liver, stomach, and pancreatic secretions and bicarbonate solutions. Most of this fluid will be absorbed by the mucous membranes in the small intestine and, to a lesser extent, the large intestine.

80 % of consumed water is absorbed by the small intestine. Water passes through the membranes of the epithelial cells that line the small intestine by solutes, especially sodium, are absorbed. Sodium is absorbed into enterocytes through transport proteins found in the luminal side of the cells. These are primarily cotransporters that move sodium and glucose or amino acids into the enterocytes. This forms an osmotic gradient that pulls water into the cell. Water continues to follow the sodium as it is pumped into the interstitial space at the basal-luminal side of the cell and then into the capillaries of the portal system. Water continues to be absorbed in the large intestine with other nutrients and vitamins.

Fluids can also be added intravenously when in the hospital. It is always preferred to provide nutrients PO (“per os” or “by mouth”) but some procedures, tests, and most surgeries require the patient to be NPO (“nil per os” or “nothing by mouth”). In these cases and when the patient is physically unable to eat due to unconsciousness or aspiration concerns nutrients and fluids are supplied intravenously. The type and rate of fluid provided can be a very powerful medical tool for treating a variety of ailments.

Flowchart Showing the Thirst Response

Image: “Flowchart Showing the Thirst Response” by PhilSchatz. License: CC BY 4.0

Water removal

Fluids are removed by three different ways: urination, defecation, and intravascular fluid loss.

The process of urination starts at the kidneys where electrolytes and other small particles are filtered out of the blood and then some material is reabsorbed or secreted into the urine which is then excreted. This process is very carefully controlled by several modulators including three hormones aldosterone, vasopressin (antidiuretic protein) and natriuretic peptide. These hormones are released in response to the body’s physiologic state to regulate plasma volume, plasma osmolality, and certain electrolyte concentrations (mostly sodium).

Water is also lost during defecation. Most fluid is reabsorbed from consumed food and drink by the small intestine, but some escapes in feces. This is an osmotic process as the food bolus travels down the gastrointestinal system. If the bolus travels too fast and has spent an insufficient time to allow for sufficient water absorption then the stool is watery, called diarrhea (a condition where there is too much fluid in the fecal matter). Young and healthy adults may not suffer any consequences from occasional diarrhea but in both the very young and elderly the water loss due to diarrhea could lead to major health concerns including dehydration, malnutrition, metabolic acidosis, and hypovolemic shock.

Uncontrolled intravascular fluid loss, as in a trauma, can also lead to hypovolemic shock. Fluid can also be removed from the intravascular space during the process of dialysis in patients with kidney injury.

Regulation of water and Na+ Balance


Normally, body fluid volumes (ECF) are rehulated by changes in Na+ balance. Normally, serum osmolality and its primary determinant, Na+ concentration, are regulated by changes in H2O balance.

  • Changes in Na+ balance → changes in volume status
  • Changes in H2O balance → changes in Na+ concentration and osmolarity
  • In certain pathologic states, there can be “crossover” between these two systems



The body has no way of measuring the extracellular fluid levels (EFC). However, through various receptors found throughout the body the effective circulating volume (ECV) can be measured. ECV is a measure of the fluid that perfuses tissue.

EFC and ECV are proportional in a healthy adult. However, in a diseased state such as congestive heart failure or cirrhosis the EFC may appear low resulting in a response by the body to retain fluids even though the EFC appears normal. The result is a hypervolemic state with peripheral edema, pulmonary edema and ascites.

Fluid Distribution Diagrams



Measuring Ions and Fluid Compartments

Basic metabolic panels Comprehensive metabolic panels
Chem-7 (SMA-7)
  • Ions: Na+, K+, CI & HCO3
  • Ions: Na+, CI-, HCO3 (CO2), Ca2+
  • Other: Glucose, BUN & Creatinine
  • Other: Glucose, BUN, Creatinine, ALP, ALT, AST, Bilirubin, TP, Albumin
Plasma, Serum & interstitial osmolality
  • Direct measurement: Freeze point depression/ vapor pressure
  • Estimated: Posm = (2 x Na) + (glucose/18) + (BUN/2.8)

Serum Total Proteins (Oncotic)

  • Total
  • Albumin
  • Globulins: α1, α2, β, γ

Changes in Body Fluid Compartment

Hypo-osmotic Volume Expansion Hypo-osmotic Volume Contraction
ECF Measurements

ABP = ↑ ↔

[Na+] = ↓

TP = ↓

Hct = ↔

Endocrine Response

Aldo = ↓

ADH = ↓

hypoosmotic-volume-expansion ECF Measurements

ABP = ↓

[Na+] = ↓

TP = ↑

Hct = ↑

Endocrine Response

Aldo = ↑

ADH = ↓ ↔

Iso-osmotic Volume Expansion Iso-osmotic Volume Contraction
ECF Measurements

ABP = ↑

[Na+] = ↔

TP = ↓

Hct = ↓

Endocrine Response

Aldo = ↓

ADH = ↔ ↓


  • IV solution
isoosmotic-volume-expansion ECF Measurements

ABP = ↓

[Na+] = ↔

TP = ↑

Hct = ↑

Endocrine Response

Aldo = ↑

ADH = ↔ ↑


  • Diarrhea
  • Vomitting
 Hyper-osmotic volume expansion  Hyper-osmotic Contraction  
ECF Measurements

ABP = ↑

[Na+] = ↑

TP = ↓

Hct = ↓

Endocrine Response

Aldo = ↓

ADH = ↑ ↔


  • Aldosterone
  • Tumor
hyperosmotic-volume-expansion ECF Measurements

ABP = ↓

[Na+] = ↑

TP = ↑

Hct = ↔

Endocrine Response

Aldo = ↑

ADH = ↑


  • Lack of water

Renin-Angiotensin-Aldosterone System

The renin-angiotensin-aldosterone system (RAAS) involves several peptide and steroid hormones to regulate fluid balance and blood pressure.

When activated, RAAS works to increase blood pressure and fluid retention and is the target of many hypertension medications including ACE inhibitors and aldosterone receptors antagonists. This system starts at the afferent arterioles of the kidney. Modified smooth muscle cells called juxtaglomerular cells located in these arterioles detect blood pressure with stretch receptors. When blood pressure drops or when they are signaled by the macula densa sensing low sodium concentration the juxtaglomerular cells release the enzyme renin into circulation.

Renin converts angiotensinogen, synthesized by the liver, into angiotensin I. This is then quickly activated by angiotensin converting enzyme (ACE), synthesized by the lungs, into angiotensin II. Angiotensin II is a strong vasoactive peptide consisting of eight residues. It affects multiple systems to increase circulating blood volume and blood pressure. It causes the afferent arterioles to constrict increasing systemic blood pressure and the sodium, chloride, and water reabsorption in the kidney.

In the brain angiotensin II stimulates the release of vasopressin (ADH) and the thirst center. It also causes the adrenal glands to release the mineralocorticoid aldosterone. Aldosterone then affects the kidney even further to increase reabsorption of sodium, chloride, and water and also secrete potassium.

The renin-angiotensin system

Image: “Overview of the renin-angiotensin system” by Mikael Häggström. License: Public Domain

Atrial Natriuretic Peptide

Atrial natriuretic peptide (ANP) works to oppose aldosterone. It is a peptide hormone that is synthesize and released by myocytes found in the atria of the heart in response to stretching (too much blood volume) or angiotensin II. In the kidney it works to increase glomerular filtration rate and excretion of sodium, chloride and water. It also relaxes systemic afferent arterioles to lower systemic blood pressure.

Antidiuretic Hormone

Antidiuretic Hormone (ADH)

Image: “Antidiuretic Hormone (ADH)” by PhilSchatz. License: CC BY 4.0

Antidiuretic hormone (ADH) or arginine vasopressin is a short peptide hormone. This hormone works to increases blood volume. ADH is released from the posterior pituitary when stimulated by low-pressure baroreceptors found in the vasculature or osmoreceptors found in the hypothalamus.

When blood volume is low these receptors send a signal to the posterior pituitary to release ADH. Osmoreceptors measure the osmotic pressure of blood. When the blood is too concentrated (too much solvent) they will shrivel as fluid shifts out of the cells by osmosis. This sends a signal to the posterior pituitary to release ADH into circulation.

There are several ADH receptors. AVPR2 is found in the basolateral side of the epithelial cells that line the collecting ducts and tubules in the kidney. When AVPR2 is stimulated multiple copies of the water transport protein aquaporin-2 are inserted into the luminal side of the collecting duct cells and water is reabsorbed down its concentration gradient and into systemic circulation.



Interaction of plasma osmolality and volume on AVP/ADH secretion

plasma osmolality

Angiotensin II and Na+ excretion


Regulation of Aldosterone



Review Questions

The correct answers can be found below the references.

1. The majority of the total body water is found in which compartment?

  1. Extracellular space
  2. Intracellular space
  3. Intravascular space
  4. Interstitial space

2. Which volume does the body measure when assessing fluid state?

  1. Effective circulating volume
  2. Intracellular volume
  3. Intravascular circulating volume
  4. Effective interstitial volume

3. Which two systems oppose each other to balance fluid levels?

  1. Effective circulating volume and intracellular volume
  2. Renin and Aldosterone
  3. Angiotensin II and Aldosterone
  4. RAAS and ANP
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