Water Balance

Regulation of Water Intake

Fluid can enter the body as preformed water, ingested food and drink, and, to a lesser extent, as metabolic water.

Learning Objectives

Describe the regulation of water intake in the body

Key Takeaways

Key Points

  • A constant supply of water is needed to replenish the fluids lost through normal physiological activities, such as respiration, sweating, and urination.
  • Thirst is a sensation created by the hypothalamus that drives organisms to ingest water.
  • Increased osmolarity in the blood acts on osmoreceptors that either stimulate the hypothalamus directly or cause the release of angiotensin II to stimulate the hypothalamus to cause thirst.
  • The renin –angiotensin system increases thirst as a way to increase blood volume. It is activated by high plasma osmolarity, low blood volume, low blood pressure, and stimulation of the sympathetic nervous system.

Key Terms

  • thirst: The sensation that drives organisms to ingest water. It is considered a basic survival instinct.
  • osmoreceptors: Sensory receptors that are primarily found in the hypothalamus or macula densa that detect changes in the solute concentration of blood.

Water Intake

Fluid can enter the body as preformed water, ingested food and drink, and, to a lesser extent, as metabolic water that is produced as a by-product of aerobic respiration and dehydration synthesis. A constant supply is needed to replenish the fluids lost through normal physiological activities, such as respiration, sweating, and urination.

Water generated from the biochemical metabolism of nutrients provides a significant proportion of the daily water requirements for some arthropods and desert animals, but it provides only a small fraction of a human’s necessary intake. In the normal resting state, the input of water through ingested fluids is approximately 2500 ml/day.

Body water homeostasis is regulated mainly through ingested fluids, which, in turn, depends on thirst. Thirst is the basic instinct or urge that drives an organism to ingest water.

Thirst is a sensation created by the hypothalamus, the thirst center of the human body. Thirst is an important component of blood volume regulation, which is slowly regulated by homeostasis.

Hypothalamus-Mediated Thirst

An osmoreceptor is a sensory receptor that detects changes in osmotic pressure and is primarily found in the hypothalamus of most homeothermic organisms. Osmoreceptors detect changes in plasma osmolarity (that is, the concentration of solutes dissolved in the blood).

When the osmolarity of blood changes (it is more or less dilute), water diffusion into and out of the osmoreceptor cells changes. That is, the cells expand when the blood plasma is more dilute and contract with a higher concentration.

When the osmoreceptors detect high plasma osmolarity (often a sign of a low blood volume), they send signals to the hypothalamus, which creates the biological sensation of thirst. Osmoreceptors also stimulate vasopressin (ADH) secretion, which starts the events that will reduce plasma osmolarity to normal levels.

The illustration shows the location of the hypothalamus in the brain. It is between the thalamus and the infundibulum. The anterior and posterior pituitary glands are seen under the infundibulum.

The hypothalamus: The hypothalamus is the thirst center of the human body.

Renin–Angiotensin System-Mediated Thirst

Another way through which thirst is induced is through angiotensin II, one of the hormones involved in the renin–angiotensin system. The renin–angiotensin system is a complex homeostatic pathway that deals with blood volume as a whole, as well as plasma osmolarity and blood pressure.

The macula densa cells in the walls of the ascending loop of Henle of the nephron is another type of osmoreceptor; however it stimulates the juxtaglomerular apparatus (JGA) instead of the hypothalamus. When the macula densa is stimulated by high osmolarity, The JGA releases renin into the bloodstream, which cleaves angiotensinogen into angiotensin I. Angiotensin I is converted into angiotensin II by ACE in the lungs. ACE is a hormone that has many functions.

Angiotensin II acts on the hypothalamus to cause the sensation of thirst. It also causes vasoconstriction, and the release of aldosterone to cause increased water reabsorption in a mechanism that is very similar to that of ADH.

Note that the renin–angiotensin system, and thus thirst, can be caused by other stimuli besides increased plasma osmolarity or a decrease in blood volume. For example, stimulation of the sympathetic nervous system and low blood pressure in the kidneys (decreased GFR) will stimulate the renin–angiotensin system and cause an increase in thirst.

Regulation of Water Output

Fluid can leave the body in three ways: urination, excretion (feces), and perspiration (sweating).

Learning Objectives

Describe the regulation of water output in humans

Key Takeaways

Key Points

  • The majority of fluid output occurs from urination. Some fluid is lost through perspiration (part of the body’s temperature control mechanism) and as water vapor in expired air.
  • The body’s homeostatic control mechanisms ensure that a balance between fluid gain and fluid loss is maintained. The hormones ADH (antidiuretic hormone, also known as vasopressin ) and aldosterone play a major role in this.
  • If the body is becoming fluid deficient, increased plasma osmolarity is sensed by the osmoreceptors. This results in an increase in the secretion of ADH that causes fluid to be retained by the kidneys and urine output to be reduced.
  • Aldosterone is the major end-product of the renin – angiotensin system, and increases the expression of ATPase pumps in the nephron that causes an increase in water reabsorption through sodium cotransport.
  • ADH increases water reabsorption by increasing the nephron’s permeability to water, while aldosterone works by increasing the reabsorption of both sodium and water.

Key Terms

  • osmoreceptors: Sensory receptors, primarily found in the hypothalamus, that detect changes in plasma osmolarity and contribute to the fluid-balance regulation in the body.
  • anti-diuretic hormone: A neurohypophysial hormone found in most mammals that is responsible for increasing water absorption in the collecting ducts of the kidney nephrons.
  • aldosterone: A corticoid hormone that is secreted by the adrenal cortex that regulates the balance of sodium and potassium and thus the water-balance levels in the body.

Water Output

Fluid can leave the body in three ways:

  1. Urination
  2. Excretion (feces)
  3. Perspiration (sweating)

The majority of fluid output occurs from urination, at approximately 1500 ml/day (approximately 1.59 qt/day) in a normal adult at resting state. Some fluid is lost through perspiration (part of the body’s temperature control mechanism) and as water vapor in expired air; however these fluid losses are considered to be very minor.

The body’s homeostatic control mechanisms maintain a constant internal environment to ensure that a balance between fluid gain and fluid loss is maintained. The hormones ADH (anti-diuretic hormone, also known as vasopressin) and aldosterone, a hormone created by the renin–angiotensin system, play a major role in this balance.

If the body is becoming fluid deficient, there will be an increase in the secretion of these hormones that causes water to be retained by the kidneys through increased tubular reabsorption and urine output to be reduced. Conversely, if fluid levels are excessive, the secretion of these hormones is suppressed and results in less retention of fluid by the kidneys and a subsequent increase in the volume of urine produced, due to reduced fluid retention.

ADH Feedback

When blood volume becomes too low, plasma osmolarity will increase due to a higher concentration of solutes per volume of water. Osmoreceptors in the hypothalamus detect the increased plasma osmolarity and stimulate the posterior pituitary gland to secrete ADH.

ADH causes the walls of the distal convoluted tubule and collecting duct to become permeable to water—this drastically increases the amount of water that is reabsorbed during tubular reabsorption. ADH also has a vasoconstrictive effect in the cardiovascular system, which makes it one of the most important compensatory mechanisms during hypovolemic shock (shock from excessive fluid loss or bleeding).

Aldosterone Feedback

Aldosterone is a steroid hormone (corticoid) produced at the end of the renin–angiotensin system. To review the renin–angiotensin system, low blood volume activates the juxtaglomerular apparatus in a variety of ways to make it secrete renin. Renin cleaves angiotensin I from the liver -produced angiotensinogen. Angiotensin converting enzyme (ACE) in the lungs converts angiotensin I into angiotensin II. Angiotensin II has a variety of effects (such as increasing thirst) but it also causes release of aldosterone from the adrenal cortex.

Aldosterone has a number of effects that are involved in the regulation of water output. It acts on mineral corticoid receptors in the epithelial cells of the distal convoluted tubule and collecting duct to increase their expression of Na+/K+ ATPase pumps and to activate those pumps. This causes greatly increased reabsorption of sodium and water (which follows sodium osmotically by cotransport), while causing the secretion of potassium into urine.

Aldosterone increases water reabsorption; however, it involves an exchange of sodium and potassium that ADH reabsoption regulation does not involve. Aldosterone will also cause a similar ion -balancing effect in the colon and salivary glands as well.

This is a diagram overview of the renin–angiotensin system that regulates blood pressure and plasma osmolarity. The hypothalamus of the brain releases a corticotropin-releasing hormone that makes the pituitary gland release ACTH to the liver which, in turn, releases angiotensinogen. Renin cleaves angiotensin I from the liver-produced angiotensinogen. Angiotensin converting enzyme (ACE) in the lungs converts angiotensin I into angiotensin II. Angiotensin II has a variety of effects (such as increasing thirst) but it also causes release of aldosterone from the adrenal cortex.

A schematic diagram of the renin–angiotensin system: Overview of the renin–angiotensin system that regulates blood pressure and plasma osmolarity.

Nitrogenous Waste in Terrestrial Animals: The Urea Cycle

Urea, a nitrogenous waste material, is the end product excreted in urine when ammonia is metabolized by animals, such as mammals.

Learning Objectives

Discuss the urea cycle

Key Takeaways

Key Points

  • Ureotelic animals, which includes mammals, produce urea as the main nitrogenous waste material.
  • 2 NH3 + CO2 + 3 ATP + H2O → H2N-CO-NH2 + 2 ADP + 4 Pi + AMP is the chemical reaction by which toxic ammonia is converted to urea.
  • The urea cycle involves the multi-step conversion (carried out by five different enzymes ) of the amino acid L- ornithine into different intermediates before being regenerated.

Key Terms

  • ureotelic: animals that secrete urea as the primary nitrogenous waste material
  • ornithine: an amino acid, which acts as an intermediate in the biosynthesis of urea
  • urea: a water-soluble organic compound, CO(NH2)2, formed by the metabolism of proteins and excreted in the urine

Nitrogenous Waste in Terrestrial Animals: The Urea Cycle

Mammals, including humans, are the primary producers of urea. Because they secrete urea as the primary nitrogenous waste product, they are called ureotelic animals. Urea serves an important role in the metabolism of nitrogen-containing compounds by animals. It is the main nitrogen-containing substance in the urine of mammals. Urea is a colorless, odorless solid, highly soluble in water, and practically non-toxic. Dissolved in water, it is neither acidic nor alkaline. The body uses it in many processes, the most notable one being nitrogen excretion. Urea is widely used in fertilizers as a convenient source of nitrogen. It is also an important raw material for the chemical industry.

Apart from mammals, urea is also found in the urine of amphibians, as well as some fish. Interestingly, tadpoles excrete ammonia, but shift to urea production during metamorphosis. In humans, apart from being a carrier of waste nitrogen, urea also plays a role in the countercurrent exchange system of the nephrons, which allows for re-absorption of water and critical ions from the excreted urine. This mechanism, controlled by an anti-diuretic hormone, allows the body to create hyperosmotic urine, which has a higher concentration of dissolved substances than the blood plasma. This mechanism is important to prevent the loss of water, to maintain blood pressure, and to maintain a suitable concentration of sodium ions in the blood plasmas.

The urea cycle is the primary mechanism by which mammals convert ammonia to urea. Urea is made in the liver and excreted in urine. The overall chemical reaction by which ammonia is converted to urea is 2 NH3 (ammonia) + CO2 + 3 ATP + H2O → H2N-CO-NH2 (urea) + 2 ADP + 4 Pi + AMP.

The urea cycle utilizes five intermediate steps, catalyzed by five different enzymes, to convert ammonia to urea. The amino acid L-ornithine is converted into different intermediates before being regenerated at the end of the urea cycle. Hence, the urea cycle is also referred to as the ornithine cycle. The enzyme ornithine transcarbamylase catalyzes a key step in the urea cycle. Its deficiency can lead to accumulation of toxic levels of ammonia in the body. The first two reactions occur in the mitochondria, while the last three reactions occur in the cytosol.

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Urea Cycle: The urea cycle converts ammonia to urea in five steps that include the catalyzation of five different enzymes.

Water Balance Disorders

Dehydration is the excessive loss of body fluid.

Learning Objectives

Describe disorders due to water balance problems

Key Takeaways

Key Points

  • There are three types of dehydration: hypotonic or hyponatremic, hypertonic or hypernatremic, and isotonic or isonatremic.
  • Hypotonic dehydration is primarily a loss of electrolytes, sodium in particular.
  • Hypertonic dehydration is primarily a loss of water.
  • Isotonic dehydration is an equal loss of water and electrolytes.
  • Hypvolemia is a loss of blood volume, and may cause hypovolemic shock. In humans, the most common type of dehydration by far is isotonic (isonatraemic) dehydration.
  • Water balance disorders are generally treated by increasing water intake and reducing or stopping fluid loss.

Key Terms

  • isotonic: When comparing solutions, an isotonic solution has the same osmolarity (ion concentration) as the solution it is being compared to.
  • plasma: The straw-colored/pale-yellow, liquid component of blood that normally holds the blood cells of whole blood in suspension.
  • electrolyte: Any of the various ions (such as sodium or chloride) that regulate the electric charge on cells and the flow of water across their membranes.

Water Balance Disorders

In physiology and medicine, dehydration (hypohydration) is defined as the excessive loss of body fluid. It is literally the removal of water from an object. However, in physiological terms, it entails a deficiency of fluid within an organism.

Much of the physiological effects of dehydration is due to the changes in ion concentration that may occur as a result of the dehydration. Alternatively, hypovolemia may occur due to loss of blood volume itself.

Dehydration

There are three types of dehydration that differ based on the type of change in ion concentrations:

  1. Hypotonic—primarily a loss of electrolytes, sodium in particular. Hypotonic dehydration causes decreased plasma osmolarity.
  2. Hypertonic—primarily a loss of water. Hypertonic dehydration causes increased plasma osmolarity.
  3. Isotonic—an equal loss of water and electrolytes. Isotonic dehydration will not change plasma osmolarity, but it will reduce overall plasma volume. Isotonic dehydration is the most common type of dehydration.

Further complications may also occur. In hypotonic dehydration, intravascular water shifts to the extravascular space and exaggerates intravascular volume depletion for a given amount of total body water loss.

Neurological complications can occur in hypotonic and hypertonic states. The former can lead to seizures, while the latter can lead to osmotic cerebral edema upon rapid rehydration.

Hypovolemia

Hypovolemia is specifically a decrease in the volume of blood plasma. Furthermore, hypovolemia defines water deficiency in terms of blood volume rather than the overall water content of the body.

This is a color photograph of IV fluid and electrolyte administration. Intravenous administration of fluid is one effective treatment of dehydration in humans.

IV fluid and electrolyte administration: Intravenous administration of fluid is one effective treatment of dehydration in humans.

Hypovolemia is a cause of hypovolemic shock. Shock is any condition in which the body’s fluids are unable to properly circulate and oxygenate the major organs of the human body; this causes compensatory mechanisms to activate that cause further bodily harm as the body’s metabolism is maintained for a while longer.

In the case of hypovolemic shock, the tissue metabolism is impaired due to a lack of blood volume and makes it difficult for red blood cells to reach all of the tissues of the body. It is most often caused by severe vomiting, diarrhea, blood loss, or hemorrhage. Other forms of shock with similar symptoms may be due to problems in the heart (cardiogenic) or bacterial infection (septic).

Treatment Options

To treat minor dehydration water intake must be increased, while the source of fluid loss must be reduced or stopped altogether. Plain water restores only the volume of the blood plasma and inhibits the thirst mechanism before solute levels can be replenished.

Solid foods can contribute to fluid loss from vomiting and diarrhea. In more severe cases, correction of a dehydrated state is accomplished by the replenishment of necessary water and electrolytes through oral rehydration therapy or fluid replacement by intravenous therapy (an IV drip).

As oral rehydration is easier to provide, it is the treatment of choice for mild dehydration. Solutions used for intravenous rehydration must be isotonic or hypotonic. Pure water injected into the veins will cause the breakdown (lysis) of red blood cells that could cause other problems.