Category Archive Science

Sodium, Electrolytes, and Fluid Balance

Electrolytes play a vital role in maintaining homeostasis within the body.

Importance of Electrolyte Balance

Electrolytes play a vital role in maintaining homeostasis within the body. They help regulate myocardial and neurological function, fluid balance, oxygen delivery, acid-base balance, and other biological processes.

Electrolytes are important because they are what cells (especially those of the nerve, heart, and muscle ) use to maintain voltages across their cell membranes and to carry electrical impulses (nerve impulses, muscle contractions) across themselves and to other cells.

Electrolyte imbalances can develop from excessive or diminished ingestion and from the excessive or diminished elimination of an electrolyte. The most common cause of electrolyte disturbances is renal failure. The most serious electrolyte disturbances involve abnormalities in the levels of sodium, potassium, and/or calcium.

Other electrolyte imbalances are less common and often occur in conjunction with major electrolyte changes. Chronic laxative abuse or severe diarrhea or vomiting (gastroenteritis) can lead to electrolyte disturbances combined with dehydration. People suffering from bulimia or anorexia nervosa are especially at high risk for an electrolyte imbalance.

Kidneys work to keep the electrolyte concentrations in blood constant despite changes in your body. For example, during heavy exercise electrolytes are lost through sweating, particularly sodium and potassium, and sweating can increase the need for electrolyte (salt) replacement. It is necessary to replace these electrolytes to keep their concentrations in the body fluids constant.

Dehydration

There are three types of dehydration:

• Hypotonic or hyponatremic (primarily a loss of electrolytes, sodium in particular).
• Hypertonic or hypernatremic (primarily a loss of water).
• Isotonic or hyponatremic (an equal loss of water and electrolytes).

In humans, the most common type of dehydration by far is isotonic (isonatraemic) dehydration; which effectively equates with hypovolemia; but the distinction of isotonic from hypotonic or hypertonic dehydration may be important when treating people with dehydration.

Physiologically, and despite the name, dehydration does not simply mean loss of water, as both water and solutes (main sodium) are usually lost in roughly equal quantities as to how they exist in blood plasma. In hypotonic dehydration, intravascular water shifts to the extravascular space and exaggerates the 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.

In more severe cases, the 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). As oral rehydration is less painful, less invasive, less expensive, and easier to provide, it is the treatment of choice for mild dehydration. Solutions used for intravenous rehydration must be isotonic or hypotonic.

Sodium Balance Regulation

Sodium is an important cation that is distributed primarily outside the cell.

Sodium Regulation

Sodium is an important cation that is distributed primarily outside the cell. The cell sodium concentration is about 15 mmol/l, but it varies in different organs; it has an intracellular volume of 30 liters and about 400 mmol are inside the cell.

The plasma and interstitial sodium is about 140 mmol/l with an extracellular volume of about 13 liters, 1,800 mmol are in the extracellular space. The total body sodium, however, is about 3,700 mmol as there is about 1,500 mmol stored in bones.

The body has potent sodium-retaining mechanisms and even if a person is on five mmol Na+/day they can maintain sodium balance. Extra sodium is lost from the body by reducing the activity of the renin –angiotensin system that leads to increased sodium loss from the body. Sodium is lost through the kidneys, sweat, and feces.

In states of sodium depletion, the aldosterone levels increase. In states of sodium excess, aldosterone levels decrease. The major physiological controller of aldosterone secretion is the plasma angiotensin II level that increases aldosterone secretion.

A high plasma potassium level also increases aldosterone secretion because, besides retaining Na+, high plasma aldosterone causes K+ loss by the kidney. Plasma Na+ levels have little effect on aldosterone secretion.

A low renal perfusion pressure stimulates the release of renin, which forms angiotensin I that is converted to angiotensin II. Angiotensin II will correct the low perfusion pressure by causing the blood vessels to constrict, and increase sodium retention by its direct effect on the proximal renal tubule and by an effect operated through aldosterone. The perfusion pressure to the adrenal gland has a little direct effect on aldosterone secretion and the low blood pressure operates to control aldosterone via the renin-angiotensin system.

Aldosterone also acts on the sweat ducts and colonic epithelium to conserve sodium. When aldosterone is activated to retain sodium the plasma sodium tends to rise. This immediately causes the release of ADH, which causes water to be retained, thus balancing Na+ and H2O in the right proportion to restore plasma volume.

In addition to aldosterone and angiotensin II, other factors influence sodium excretion.

• Atrial peptide causes the loss of sodium by the kidneys: it is secreted from the heart in high sodium states due to excess intake or cardiac disease.
• Elevated blood pressure will also cause Na+ loss, and low blood pressure usually leads to sodium retention.

Potassium Balance Regulation

Potassium is mainly an intracellular ion.

Potassium Balance

Potassium is predominantly an intracellular ion. Most of the total body potassium of about 4,000 mmol is inside the cells, and the next largest proportion (300–500 mmol) is in the bones. Cell K+ concentration is about 150 mmol/l but varies in different organs. Extracellular potassium is about 4.0 mmol/l, with an extracellular value of about 13 liters, 52 mmol (i.e., less than 1.5%) is present here and only 12 mmol is in the plasma.

In an unprocessed diet, potassium is much more plentiful than sodium. It is present as an organic salt, while sodium is added as NaCl. In a hunter-gatherer, K+ intake may be as much as 400 mmol/d while in the Western diet it is 70 mmol/d or less if a person has a minimal amount of fresh fruit and vegetables.

The processing of foods replaces K+ with NaCl. While the body can excrete a large K+ load, it is unable to conserve K+. On a zero K+ intake, or in a person with K+ depletion, there will still be a loss of K+ of 30–50 mmol/d in the urine and feces.

Acid-Base Status Control

If there is a high potassium intake, for example, 100 mmol, this would potentially increase the extracellular K+ level two times before the kidney could excrete the extra potassium. The body buffers the extra potassium by equilibrating it within the cells.

The acid-base status controls the distribution between plasma and cells. A high pH (i.e., alkalosis >7.4) favors the movement of K+ into the cells, and a low pH (i.e., acidosis ) causes movement out of the cell. A high plasma potassium level increases aldosterone secretion and this increases the potassium loss from the body to restore balance.

This change of distribution with the acid-base status means that the plasma K+ may not reflect the total body content. Therefore, a person with acidosis (pH 7.1) and a plasma K+ of 6.5 mmol/l could be depleted of total body potassium. This occurs in diabetic acidosis. Conversely, a person who is alkalotic with a plasma K+ of 3.4 mmol/l may have a normal level of total body potassium.

Calcium and Phosphate Balance Regulation

Calcium is a key electrolyte: 99% is deposited in the bones and the remainder is associated with hormone release and cell signaling.

Calcium is a very important electrolyte. Ninety-nine percent or more is deposited in the bones and the remainder plays a vital role in nerve conduction, muscle contraction, hormone release, and cell signaling.

The plasma concentration of Ca++ is 2.2 mmol/l, and phosphate is 1.0 mmol/l. The solubility product of Ca and P is close to saturation in plasma. The concentration of Ca++ in the cytoplasm is < 10–6 mmol/l but the concentration of Ca++ in the cell is much higher as calcium is taken up (and is able to be released from) cell organelles.

In the typical Australian diet, there is about 1200 mg/d of calcium. Even if it was all soluble it is not all absorbed as it combines with phosphates in the intestinal secretions. In addition, absorption is regulated by the active vitamin D; increased amounts of vitamin D increase Ca++ absorption.

Absorption is controlled by vitamin D while excretion is controlled by parathyroid hormones. However, the distribution from bone to plasma is controlled by both the parathyroid hormones and vitamin D.

There is also a constant loss of calcium via the kidneys even if there is none in the diet. This excretion of calcium by the kidneys and its distribution between bone and the rest of the body is primarily controlled by the parathyroid hormone.

The calcium in plasma exists in three forms:

1. Ionized.
2. Nonionized.
3. Protein-bound.

It is the ionized calcium concentration that is monitored by the parathyroid gland —if it is low, parathyroid hormone secretion is increased. This increases the ionized calcium levels by increasing bone re-absorption, decreasing renal excretion, and acting on the kidney to increase the rate of formation of active vitamin D, thereby increasing the gut’s absorption of calcium.

The usual amount of phosphate in the diet is about 1 g/d but not all of it is absorbed. Any excess is excreted by the kidney and this excretion is increased by the parathyroid hormone.

This hormone also causes phosphate to leach out of the bones. Plasma phosphate has no direct effect on parathyroid hormone secretion; however, if it is elevated it combines with Ca++ to decrease ionized Ca++ in plasma, and thereby increase parathyroid hormone secretion.

Anion Regulation

The anions chloride, bicarbonate, and phosphate have important roles in maintaining the balance and neutrality of vital body mechanisms.

Anion Regulation

The excretion of ions occurs mainly through the kidneys, with lesser amounts of ions being lost in sweat and in feces. In addition, excessive sweating may cause a significant loss, especially of the anion chloride. Severe vomiting or diarrhea will also cause a loss of chloride and bicarbonate ions.

Adjustments in the respiratory and renal functions allow the body to regulate the levels of these ions in the extracellular fluid (ECF).

Chloride

Chloride is the predominant extracellular anion and it is a major contributor to the osmotic pressure gradient between the intracellular fluid (ICF) and extracellular fluid (ECF). Chloride maintains proper hydration and functions to balance the cations in the ECF to keep the electrical neutrality of this fluid. The paths of secretion and reabsorption of chloride ions in the renal system follow the paths of sodium ions.

Hypochloremia, or lower-than-normal blood chloride levels, can occur because of defective renal tubular absorption. Vomiting, diarrhea, and metabolic acidosis can also lead to hypochloremia.

In contrast, hyperchloremia, or higher-than-normal blood chloride levels, can occur due to dehydration, excessive intake of dietary salt (NaCl) or the swallowing of sea water, aspirin intoxication, congestive heart failure, and the hereditary, chronic lung disease cystic fibrosis. In people who have cystic fibrosis, the chloride levels in their sweat are two to five times those of normal levels; therefore, analysis of their sweat is often used to diagnose the disease.

Bicarbonate

Bicarbonate is the second-most abundant anion in the blood. Its principal function is to maintain your body’s acid–base balance by being part of buffer systems.

Bicarbonate ions result from a chemical reaction that starts with the carbon dioxide (CO₂) and water (H₂O) molecules that are produced at the end of aerobic metabolism. Only a small amount of CO₂ can be dissolved in body fluids; thus, over 90 percent of the CO₂ is converted into bicarbonate ions, HCO₃-, through the following reactions:

CO₂ + H₂O ↔ H₂CO₃ ↔ H₂CO₃– + H+

The bidirectional arrows indicate that the reactions can go in either direction depending on the concentrations of the reactants and products. Carbon dioxide is produced in large amounts in tissues that have a high metabolic rate, and is converted into bicarbonate in the cytoplasm of the red blood cells through the action of an enzyme called carbonic anhydrase.

Bicarbonate is transported in the blood and once in the lungs, the reactions reverse direction, and CO₂ is regenerated from the bicarbonate to be exhaled as metabolic waste.

Phosphate

Phosphate is present in the body in three ionic forms:

1. H₂PO₄−
2. HPO₄²⁻
3. PO₄³⁻

The addition and removal of phosphate from the proteins in all cells is a pivotal strategy in the regulation of metabolic processes. Phosphate is useful in animal cells as a buffering agent, and the most common form is HPO²⁻₄. Bone and teeth bind up 85 percent of the body’s phosphate as part of calcium phosphate salts. In addition, phosphate is found in phospholipids, such as those that make up the cell membrane, and in ATP, nucleotides, and buffers.

Hypophosphatemia, or abnormally low phosphate blood levels, occurs with the heavy use of antacids, during alcohol withdrawal, and during malnourishment. In the face of phosphate depletion, the kidneys usually conserve phosphate, but during starvation, this conservation is impaired greatly.

Hyperphosphatemia, or abnormally increased levels of phosphates in the blood, occurs if there is decreased renal function or in cases of acute lymphocytic leukemia. Additionally, because phosphate is a major constituent of the ICF, any significant destruction of cells can result in the dumping of phosphate into the ECF.

Regulation of Water Intake

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

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 osmolality to normal levels.

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 osmolality 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).

Water Output

Fluid can leave the body in three ways:

• Urination
• Excretion (feces)
• 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 increased thirst) but it also causes the 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 the urine.

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

Nitrogenous Waste in Terrestrial Animals: The Urea Cycle

A general water balance equation is:^[rx]

P = R + ET + ΔS

where

P is precipitation is streamflow is evapotranspiration

ΔS is the change in storage (in soil or the bedrock/groundwater)

This equation uses the principles of conservation of mass in a closed system, whereby any water entering a system (via precipitation), must be transferred into either evaporation, transpiration, surface runoff (eventually reaching the channel and leaving in the form of river discharge), or stored in the ground. This equation requires the system to be closed, and where it isn’t (for example when surface runoff contributes to a different basin), this must be taken into account.

Extensive water balances are discussed in agricultural hydrology.

A water balance can be used to help manage water supply and predict where there may be water shortages. It is also used in irrigation, runoff assessment (e.g. through the RainOff model ^[rx]), flood control, and pollution control. Further, it is used in the design of subsurface drainage systems which may be horizontal (i.e. using pipes, tile drains, or ditches) or vertical (drainage by wells).^[rx] To estimate the drainage requirement, the use of a hydrogeological water balance and a groundwater model (e.g. SahysMod^[rx]) may be instrumental.

The water balance can be illustrated using a water balance graph which plots levels of precipitation and evapotranspiration often on a monthly scale.

Several monthly water balance models had been developed for several conditions and purposes. Monthly water balance models had been studied since the 1940s.^[rx]

Water Balance of a System

“Making water available for its many uses and users requires tools and institutions to transform it from a natural resource to one providing services”.^[rx] This means that there are two types of water systems: Water Resource System (WRS) and Water Use System (WUS).

A WRS, such as a river, an aquifer, or a lake, must obey water balance. For example, the volume of water that goes into an aquifer must be equal to the amount that leaves it plus its change in storage. Under various drivers, such as climate change, population increase, and bad management, water storage of many WRS is decreasing, say per decade. This means that the volume of water in a WRS decreased after a decade, i.e., the inflow was less than outflow during that time interval.^[rx]

In general, a WUS is a water construct of a user, such as a city, an industry, an irrigation zone, or a region, and not a geographic area. The schematic of a WUS shows the inflows and the outflows. For a WUS, change in storage is negligible (relative to its inflow) under a proper time interval, hence water balance becomes inflow equal to outflow with nine Water Path Types (WPT):^[rx]

{\displaystyle VA+OS+PP=ET+NR+RF+RP}

Of course, instead of a river, it could be an aquifer that supplies water to a WUS as the main source. Let us briefly examine an urban water supply on an annual basis as a simplified example. It has negligible ET and PP (WUS is a piped network), has some limited amount of water from groundwater (OS), has return flow to the main source (RF) after passing through a Wastewater Treatment Plant, and RP type has various Water Path Instances (WPI), such as leakage, and water is taken to irrigate green zones. Considering that the annual change in storage of an urban area is negligible, the water balance equation becomes

{\displaystyle VA_{riv}+OS_{gw}=NR+RF_{wwtp}+RP_{leak}+RP_{irr}}

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

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 the re-absorption of water and critical ions from the excreted urine. This mechanism, controlled by an antidiuretic 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, maintain blood pressure, and 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 the 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 P_i + 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 the 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.

Water Balance Disorders

Dehydration is the excessive loss of body fluid.

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:

• Hypotonic – primarily a loss of electrolytes, sodium in particular. Hypotonic dehydration causes decreased plasma osmolality.
• Hypertonic – primarily a loss of water. Hypertonic dehydration causes increased plasma osmolality.
• 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.

Regulation of Water Intake

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

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 osmolality to normal levels.

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 osmolality 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).

Water Output

Fluid can leave the body in three ways:

• Urination
• Excretion (feces)
• 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 increased thirst) but it also causes the 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 the urine.

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

Nitrogenous Waste in Terrestrial Animals: The Urea Cycle

A general water balance equation is:^[rx]

P = R + ET + ΔS

where

P is precipitation is streamflow is evapotranspiration

ΔS is the change in storage (in soil or the bedrock/groundwater)

This equation uses the principles of conservation of mass in a closed system, whereby any water entering a system (via precipitation), must be transferred into either evaporation, transpiration, surface runoff (eventually reaching the channel and leaving in the form of river discharge), or stored in the ground. This equation requires the system to be closed, and where it isn’t (for example when surface runoff contributes to a different basin), this must be taken into account.

Extensive water balances are discussed in agricultural hydrology.

A water balance can be used to help manage water supply and predict where there may be water shortages. It is also used in irrigation, runoff assessment (e.g. through the RainOff model ^[rx]), flood control, and pollution control. Further, it is used in the design of subsurface drainage systems which may be horizontal (i.e. using pipes, tile drains, or ditches) or vertical (drainage by wells).^[rx] To estimate the drainage requirement, the use of a hydrogeological water balance and a groundwater model (e.g. SahysMod^[rx]) may be instrumental.

The water balance can be illustrated using a water balance graph which plots levels of precipitation and evapotranspiration often on a monthly scale.

Several monthly water balance models had been developed for several conditions and purposes. Monthly water balance models had been studied since the 1940s.^[rx]

Water Balance of a System

“Making water available for its many uses and users requires tools and institutions to transform it from a natural resource to one providing services”.^[rx] This means that there are two types of water systems: Water Resource System (WRS) and Water Use System (WUS).

A WRS, such as a river, an aquifer, or a lake, must obey water balance. For example, the volume of water that goes into an aquifer must be equal to the amount that leaves it plus its change in storage. Under various drivers, such as climate change, population increase, and bad management, water storage of many WRS is decreasing, say per decade. This means that the volume of water in a WRS decreased after a decade, i.e., the inflow was less than outflow during that time interval.^[rx]

In general, a WUS is a water construct of a user, such as a city, an industry, an irrigation zone, or a region, and not a geographic area. The schematic of a WUS shows the inflows and the outflows. For a WUS, change in storage is negligible (relative to its inflow) under a proper time interval, hence water balance becomes inflow equal to outflow with nine Water Path Types (WPT):^[rx]

{\displaystyle VA+OS+PP=ET+NR+RF+RP}

Of course, instead of a river, it could be an aquifer that supplies water to a WUS as the main source. Let us briefly examine an urban water supply on an annual basis as a simplified example. It has negligible ET and PP (WUS is a piped network), has some limited amount of water from groundwater (OS), has return flow to the main source (RF) after passing through a Wastewater Treatment Plant, and RP type has various Water Path Instances (WPI), such as leakage, and water is taken to irrigate green zones. Considering that the annual change in storage of an urban area is negligible, the water balance equation becomes

{\displaystyle VA_{riv}+OS_{gw}=NR+RF_{wwtp}+RP_{leak}+RP_{irr}}

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

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 the re-absorption of water and critical ions from the excreted urine. This mechanism, controlled by an antidiuretic 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, maintain blood pressure, and 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 the 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 P_i + 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 the 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.

Water Balance Disorders

Dehydration is the excessive loss of body fluid.

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:

• Hypotonic – primarily a loss of electrolytes, sodium in particular. Hypotonic dehydration causes decreased plasma osmolality.
• Hypertonic – primarily a loss of water. Hypertonic dehydration causes increased plasma osmolality.
• 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.

Hormonal Responses to Food

The endocrine system controls the release of hormones responsible for starting, stopping, slowing, and quickening digestive processes.

Hormonal Responses to Food

The endocrine system controls the response of the various glands in the body and the release of hormones at the appropriate times. The endocrine system’s effects are slow to initiate but prolonged in their response, lasting from a few hours up to weeks. The system is made of a series of glands that produce chemicals called hormones. These hormones are chemical mediators released from endocrine tissue into the bloodstream where they travel to the target tissue and generate a response.

One of the important factors under hormonal control is the stomach acid environment. During the gastric phase, the hormone gastrin is secreted by G cells in the stomach in response to the presence of proteins. Gastrin stimulates the release of stomach acid, or hydrochloric acid (HCl), which aids in the digestion of the majority of proteins. However, when the stomach is emptied, the acidic environment need not be maintained and a hormone called somatostatin stops the release of hydrochloric acid. This is controlled by a negative feedback mechanism.

In the duodenum, digestive secretions from the liver, pancreas, and gallbladder play an important role in digesting chyme during the intestinal phase. In order to neutralize the acidic chyme, a hormone called secretin stimulates the pancreas to produce an alkaline bicarbonate solution and deliver it to the duodenum. Secretin acts in tandem with another hormone called cholecystokinin (CCK). Not only does CCK stimulate the pancreas to produce the requisite pancreatic juices, it also stimulates the gallbladder to release bile into the duodenum.

Another level of hormonal control occurs in response to the composition of food. Foods high in lipids (fatty foods) take a long time to digest. A hormone called gastric inhibitory peptide is secreted by the small intestine to slow down the peristaltic movements of the intestine to allow fatty foods more time to be digested and absorbed.

Understanding the hormonal control of the digestive system is an important area of ongoing research. Scientists are exploring the role of each hormone in the digestive process and developing ways to target these hormones. Advances could lead to knowledge that may help to battle the obesity epidemic.

Neural Responses to Food

All three phases of digestive responses to food (the cephalic, gastric, and intestinal stages) are managed through enzymatic neural control.

Neural Responses to Food

In reaction to the smell, sight, or thought of food, the first hormonal response is that of salivation. The salivary glands secrete more saliva in response to the stimulus presented by food in preparation for digestion. Simultaneously, the stomach begins to produce hydrochloric acid to digest the food. Recall that the peristaltic movements of the esophagus and other organs of the digestive tract are under the control of the brain. The brain prepares these muscles for movement as well. When the stomach is full, the part of the brain that detects satiety signals fullness. There are three overlapping phases of gastric control: the cephalic phase, the gastric phase, and the intestinal phase. Each requires many enzymes and is under neural control as well.

 

Salivation: Seeing a plate of food triggers the secretion of saliva in the mouth and the production of hydrochloric acid in the stomach.

Digestive Phases

The response to food begins even before food enters the mouth. The first phase of ingestion, called the cephalic phase, is controlled by the neural response to the stimulus provided by food. All aspects, such as sight, sense, and smell, trigger the neural responses resulting in salivation and secretion of gastric juices. The gastric and salivary secretion in the cephalic phase can also take place at the thought of food. Right now, if you think about a piece of chocolate or a crispy potato chip, the increase in salivation is a cephalic phase response to the thought. The central nervous system prepares the stomach to receive food.

The gastric phase begins once the food arrives in the stomach. It builds on the stimulation provided during the cephalic phase. Gastric acids and enzymes process the ingested materials. The gastric phase is stimulated by (1) distension of the stomach, (2) a decrease in the pH of the gastric contents, and (3) the presence of undigested material. This phase consists of local, hormonal, and neural responses. These responses stimulate secretions and powerful contractions.

The intestinal phase begins when chyme enters the small intestine, triggering digestive secretions. This phase controls the rate of gastric emptying. In addition to gastric emptying, when chyme enters the small intestine, it triggers other hormonal and neural events that coordinate the activities of the intestinal tract, pancreas, liver, and gallbladder.

Food Energy and ATP

Animals use energy for metabolism, obtaining that energy from the breakdown of food through the process of cellular respiration.

Food Energy and ATP

Animals need food to obtain energy and maintain homeostasis. Homeostasis is the ability of a system to maintain a stable internal environment even in the face of external changes to the environment. For example, the normal body temperature of humans is 37°C (98.6°F). Humans maintain this temperature even when the external temperature is hot or cold. The energy it takes to maintain this body temperature is obtained from food.

The primary source of energy for animals is carbohydrates, primarily glucose: the body’s fuel. The digestible carbohydrates in an animal’s diet are converted to glucose molecules and into energy through a series of catabolic chemical reactions.

Adenosine triphosphate, or ATP, is the primary energy currency in cells. ATP stores energy in phosphate ester bonds, releasing energy when the phosphodiester bonds are broken: ATP is converted to ADP and a phosphate group. ATP is produced by the oxidative reactions in the cytoplasm and mitochondrion of the cell, where carbohydrates, proteins, and fats undergo a series of metabolic reactions collectively called cellular respiration.

 

ATP production pathways: ATP is the energy molecule of the cell. It is produced through various pathways during the cellular respiration process, with each making different amounts of energy.

ATP is required for all cellular functions. It is used to build the organic molecules that are required for cells and tissues. It also provides energy for muscle contraction and for the transmission of electrical signals in the nervous system. When the amount of ATP available is in excess of the body’s requirements, the liver uses the excess ATP and excess glucose to produce molecules called glycogen (a polymeric form of glucose) that is stored in the liver and skeletal muscle cells. When blood sugar drops, the liver releases glucose from stores of glycogen. Skeletal muscle converts glycogen to glucose during intense exercise. The process of converting glucose and excess ATP to glycogen and the storage of excess energy is an evolutionarily important step in helping animals deal with mobility, food shortages, and famine.

Homeostatic Process

Homeostatic processes ensure a constant internal environment by various mechanisms working in combination to maintain setpoints.

Homeostatic Process

The human organism consists of trillions of cells working together for the maintenance of the entire organism. While cells may perform very different functions, the cells are quite similar in their metabolic requirements. Maintaining a constant internal environment with everything that the cells need to survive (oxygen, glucose, mineral ions, waste removal, etc.) is necessary for the well-being of individual cells and the well-being of the entire body. The varied processes by which the body regulates its internal environment are collectively referred to as homeostasis.

Homeostasis

Homeostasis, in a general sense, refers to stability, balance, or equilibrium. Physiologically, it is the body’s attempt to maintain a constant and balanced internal environment, which requires persistent monitoring and adjustments as conditions change. Adjustment of physiological systems within the body is called homeostatic regulation, which involves three parts or mechanisms: (1) the receptor, (2) the control center, and (3) the effector.

The receptor receives information that something in the environment is changing. The control center or integration center receives and processes information from the receptor. The effector responds to the commands of the control center by either opposing or enhancing the stimulus. This ongoing process continually works to restore and maintain homeostasis. For example, during body temperature regulation, temperature receptors in the skin communicate information to the brain (the control center) which signals the effectors: blood vessels and sweat glands in the skin. As the internal and external environment of the body is constantly changing, adjustments must be made continuously to stay at or near a specific value: the set point.

Purpose of Homeostasis

The ultimate goal of homeostasis is the maintenance of equilibrium around the set point. While there are normal fluctuations from the setpoint, the body’s systems will usually attempt to revert to it. A change in the internal or external environment (a stimulus) is detected by a receptor; the response of the system is to adjust the deviation parameter toward the set point. For instance, if the body becomes too warm, adjustments are made to cool the animal. If the blood glucose rises after a meal, adjustments are made to lower the blood glucose level by moving the nutrient into tissues in the command center that require it, or storing it for later use.

Homeostasis: Thermoregulation

Animals use different modes of thermoregulation processes to maintain homeostatic internal body temperatures.

Thermoregulation to Maintain Homeostasis

Internal thermoregulation contributes to an animal’s ability to maintain homeostasis within a certain range of temperatures. As internal body temperature rises, physiological processes are affected, such as enzyme activity. Although enzyme activity initially increases with temperature, enzymes begin to denature and lose their function at higher temperatures (around 40-50 C for mammals). As internal body temperature decreases below normal levels, hypothermia occurs and other physiological processes are affected. There are various thermoregulation mechanisms that animals use to regulate their internal body temperature.

Types of Thermoregulation (Ectothermy vs. Endothermy)

Thermoregulation in organisms runs along a spectrum from endothermy to ectothermy. Endotherms create most of their heat via metabolic processes, and are colloquially referred to as “warm-blooded.” Ectotherms use external sources of temperature to regulate their body temperatures. Ectotherms are colloquially referred to as “cold-blooded” even though their body temperatures often stay within the same temperature ranges as warm-blooded animals.

Ectotherm

An ectotherm, from the Greek (ektós) “outside” and (thermós) “hot,” is an organism in which internal physiological sources of heat are of relatively small or quite negligible importance in controlling body temperature. Since ectotherms rely on environmental heat sources, they can operate at economical metabolic rates. Ectotherms usually live in environments in which temperatures are constant, such as the tropics or the ocean. Ectotherms have developed several behavioral thermoregulation mechanisms, such as basking in the sun to increase body temperature or seeking shade to decrease body temperature.

Endotherms

In contrast to ectotherms, endotherms regulate their own body temperature through internal metabolic processes and usually maintain a narrow range of internal temperatures. Heat is usually generated from the animal’s normal metabolism, but under conditions of excessive cold or low activity, an endotherm generates additional heat by shivering. Many endotherms have a larger number of mitochondria per cell than ectotherms. These mitochondria enable them to generate heat by increasing the rate at which they metabolize fats and sugars. However, endothermic animals must sustain their higher metabolism by eating more food more often. For example, a mouse (endotherm) must consume food every day to sustain high its metabolism, while a snake (ectotherm) may only eat once a month because its metabolism is much lower.

Homeothermy vs. Poikilothermy

A poikilotherm is an organism whose internal temperature varies considerably. It is the opposite of a homeotherm, an organism that maintains thermal homeostasis. Poikilotherm’s internal temperature usually varies with the ambient environmental temperature, and many terrestrial ectotherms are poikilothermic. Poikilothermic animals include many species of fish, amphibians, and reptiles, as well as birds and mammals that lower their metabolism and body temperature as part of hibernation or torpor. Some ectotherms can also be homeotherms. For example, some species of tropical fish inhabit coral reefs that have such stable ambient temperatures that their internal temperature remains constant.

Means of Heat Transfer

Heat can be exchanged between an animal and its environment through four mechanisms: radiation, evaporation, convection, and conduction. Radiation is the emission of electromagnetic “heat” waves. Heat radiates from the sun and from dry skin the same manner. When a mammal sweats, evaporation removes heat from a surface with a liquid. Convection currents of air remove heat from the surface of dry skin as the air passes over it. Heat can be conducted from one surface to another during direct contact with the surfaces, such as an animal resting on a warm rock.

Heat Conservation and Dissipation

Animals have processes that allow for heat conservation and dissipation in order to maintain a homeostatic internal body temperature.

Heat Conservation and Dissipation

Animals conserve or dissipate heat in a variety of ways. In certain climates, endothermic animals have some form of insulation, such as fur, fat, feathers, or some combination thereof. Animals with thick fur or feathers create an insulating layer of air between their skin and internal organs. Polar bears and seals live and swim in a subfreezing environment, yet they maintain a constant, warm, body temperature. The arctic fox uses its fluffy tail as extra insulation when it curls up to sleep in cold weather. Mammals have a residual effect from shivering and increased muscle activity: arrector pili muscles create “goosebumps,” causing small hairs to stand up when the individual is cold; this has the intended effect of increasing body temperature. Mammals use layers of fat to achieve the same end; the loss of significant amounts of body fat will compromise an individual’s ability to conserve heat.

Endotherms use their circulatory systems to help maintain body temperature. For example, vasodilation brings more blood and heat to the body’s surface, facilitating radiation and evaporative heat loss, which helps to cool the body. However, vasoconstriction reduces blood flow in peripheral blood vessels, forcing blood toward the core and the vital organs found there, conserving heat. Some animals have adaptions to their circulatory system that enable them to transfer heat from arteries to veins, thus, warming blood that returns to the heart. This is called a countercurrent heat exchange; it prevents cold venous blood from cooling the heart and other internal organs. This adaption, which can be shut down in some animals to prevent overheating the internal organs, is found in many animals, including dolphins, sharks, bony fish, bees, and hummingbirds. In contrast, similar adaptations (as in dolphin flukes and elephant ears) can help cool endotherms when needed.

Many animals, especially mammals, use metabolic waste heat as a heat source. When muscles are contracted, most of the energy from the ATP used in muscle actions is wasted energy that translates into heat. In cases of severe cold, a shivering reflex is activated that generates heat for the body. Many species also have a type of adipose tissue called brown fat that specializes in generating heat.

Exothermic animals use changes in their behavior to help regulate body temperature. For example, a desert ectothermic animal may simply seek cooler areas during the hottest part of the day in the desert to keep from becoming too warm. The same animals may climb onto rocks to capture heat during a cold desert night. Some animals seek water to aid evaporation in cooling them, as seen with reptiles. Other ectotherms use group activity, such as the activity of bees to warm a hive to survive winter.