Site author Richard Steane
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Control of blood water potential

Balancing the aqueous inputs and outputs

Water can be gained from food and drink we ingest, and mineral salts - principally sodium chloride, common salt - are also part of our diet. This varies from person to person, and at different times of our life and the season. Respiration produces water, from the oxidation of hydrogen in carbohydrates and fats. Our other body reactions produce products which dissolve in water and enter the blood. Urea, produced in the liver as a result of deamination of excess amino acids, is an example of this.

It is important that most of these products are removed from the blood, as it is circulating to reach all the cells of the body.

The removal of metabolic products is the process of excretion, and it also involves the loss of water, in urine or air breathed out, as well as in faeces - which biologists generally do not count as an excretory product. In hot conditions we sweat, and lose both water and salt from the body as a result.

The liquid fraction of blood - the plasma - is mostly water: 90-92% water, and 8-10% solutes.

It is important to control the relative amounts of water and compounds dissolved in it - in order to maintain the 'osmotic balance'. This homeostatic process is called osmoregulation. This may be described as the control of the water potential of the blood.

An animal cell surrounded by (pure/distilled) water will absorb water by osmosis and swell up, perhaps to the point of bursting (lysis). On the other hand it will lose water by osmosis and shrink in volume when surrounded by a more concentrated solution, like seawater.

In each of these cases water moves to the region with a more negative water potential, i.e. water moves down a water potential gradient.

In the human body, it is important to prevent these effects. The water potential of blood is monitored within the hypothalamus, and the pituitary gland uses hormonal control to co-ordinate the action of the kidneys in removing excess water or solutes from the body. This is in addition to the excretion of body wastes e.g. urea and the removal of other substances e.g. drugs.

Typical water and salt inputs and outputs
for an adult male over a 24 hour period
Waterfood625expired air400
/ cm3fluids1875sweat900
/ g perfaeces0.25
There may be some variation from these figures.
An often recommended value for daily water intake is 3.5 litres.
Most people consume too much salt - on average 9-12 g per day.
The recommended maximum level of intake is 6 g.

Water potential - ψ or ψw - is a term that quantifies the tendency of water to move from one area to another. Pure water has a water potential of 0 (zero), and a solution (consisting of solute(s) dissolved in water) has a negative water potential. Water potential is typically expressed in terms of potential energy per unit volume, so pressure units are used. See osmotic pressure opposite.

In living systems water potential may be caused by a number of factors, principally osmosis, but also due to (mechanical) pressure - liquids being 'pumped' or other forms of mass transport.

These other components are often given a potential of their own: ψπ is the solute or osmotic potential, and ψp is the pressure potential.

The problem with salt

Salt - sodium chloride - is not poisonous, and the body needs it for fluid balance within cells. However excess salt in our diet causes our body to retain more water, in order to balance its osmotic effects. This increases the volume of blood, raises the blood pressure and puts more stress on the heart. It may thus cause a heart attack, stroke or kidney problems.

Blood sweat and tears . . .

We all know that body fluids consist of water and various dissolved substances that make them rather salty. Of couse salt is sodium chloride, and at this level it is more appropriate to refer to the individual ions concerned.
Sodium ions (Na+), potassium ions (K+), chloride ions (Cl-) hydrogencarbonate ions (HCO3-) [AKA bicarbonate ions], and calcium ions Ca2+ are the main ones in blood plasma.
In combination, they all contribute to the osmolarity of body fluids, even though their individual concentrations can be expressed in terms of molarity.

Osmolarity and tonicity

These are other methods of expressing and comparing the relative concentration of water and solutes in liquids.

Osmolarity takes into account the number of particles in solution: most "salts" dissociate into at least 2 ions. The (combined) osmolarity of blood is about 300 mOsm/L, equivalent to about 8.8 grams of sodium chloride - NaCl - per litre.

This is considered to be practically isotonic to - having the same solute concentation as - "normal saline" which has a number of uses in medicine and physiology. This consists of a 0.90 % w/v solution of NaCl.

Many people are familiar with isotonic sports drinks which are formulated to help people rehydrate during or after exercise, although the term can be confusing if it over-emphasises the supply of energy via carbohydrates.

Tonicity can be used as a comparative term, used with the prefixes hypo- and hyper-. Blood plasma is hypertonic to distilled water, and in osmosis water moves from a hypotonic to a hypertonc solution.

Osmotic pressure

We can calculate the osmotic pressure of a solution, π, using the following equation:

Osmotic pressure π = MRT

M is the (os)molar concentration of solute (units : mol/L)
R is the ideal gas constant (0.08206 L atm mol-1 K-1)
T is the temperature on the Kelvin scale (°C + 273) This is 310 for a human body at 37 °C

So 0.300 mOsm/L is equivalent to 7.63 atm. (0.773 MPa)
The water potential of blood plasma may thus be taken to be -0.773 MPa.

What not to do after a marathon

Obviously exercise causes us to get hot and sweaty, and to feel thirsty.

But if we drink a lot of cold water, the osmotic balance within the body can be upset. The rapid intake of water dilutes the solutes within the bloodstream, which may have a number of consequences.

In particular it can cause hyponatremia, which is a low sodium concentration in the blood. This is defined by a sodium concentration of less than 135 mmol/L (135 mEq/L), and severe hyponatremia being below 120 mEq/L.

Hyponatremia can cause problems with the brain: headache, thinking impairment, nausea and dizziness, and it can lead to confusion, seizures, and coma. Muscle cramps are another consequence.

This may be clinically reversed by the intravenous administration of controlled amounts of sodium chloride over an extended time period.

Exercise-associated hyponatremia was initially described in the 1980s in endurance athletes, and since then 'overdrinking beyond thirst' has been conclusively identified as the cause.

There have in fact been a number of deaths of athletes from complications associated with brain damage due to hyponatremia.

ADH production and release

Diuresis is production of urine: Diuretics increase it - Antidiuretics decrease it
ADH - antidiuretic hormone - also known as (arginine) vasopressin - AVP - is a hormone produced in neurones in the hypothalamus (on the undersurface of the brain).

It is passed down axons to the posterior pituitary and stored there in vesicles.

If the water potential of the surrounding extracellular fluid falls (osmolarity or tonicity rises) as a result of water being lost, this is detected by osmoreceptors in the hypothalamus.

This then causes the release of ADH into the blood circulation and it passes to the kidneys (as well as the rest of the body).

Baroreceptors which detect low blood pressure/reduced blood volume also stimulate ADH release.

The hypothalamus also generates feelings of thirst in response to falling blood water potential, so as a result we are more likely to top up with drinks containing water.

Other hormones of little/no significance in this context

Also from the posterior pituitary (neurohypophysis): oxytocin (similar molecule)
from the anterior pituitary (adenohypophysis):(via releasing factors) FSH, LH ,TSH, prolactin, ACTH, GH,etc

For the purpose of comparison within this account, it is worth bearing the following in mind.
If the osmolarity of blood passing through the hypothalamus rises above 300 mOsm/L then ADH is released and in the final stages in the kidney this causes water to be reabsorbed into the blood (bringing the osmolarity back down to 300 mOsm/L).

Structure of the nephron

The basic unit of kidney function is a structure called a nephron, or a kidney tubule, and there are about a million in each kidney.

Within to the outer section (cortex) of the kidney there is a cup-shaped capsule enclosing a glomerulus - a ball-shaped knot of blood capillaries.

This leads on into a tubular section, with several distinct sections : Each of these parts may be given extra descriptive words which tell more about their functions and specialisation: thick and thin sections of the loop, early and late sections in the convoluted tubules

The nephron is served with an extensive blood supply.

There is a branch from the renal artery (afferent arteriole) supplying blood to the glomerulus, and a slightly narrower efferent arteriole leaving it. This leads to capillaries surrounding the convoluted sections, in between which is a network of capillaries (vasa recta) crossing over and surrounding the loop of Henle. These capillaries lead back out eventually to the renal vein.

This account will cover the processes occurring in each section of the nephron.

A single nephron

nephron (152K)

The distal convoluted tubule coils back towards the glomerulus.

The juxtaglomerular apparatus is between the afferent arteriole and the distal convoluted tubule of the same nephron.

Its function in regulation of renal blood flow and glomerular filtration rate.

Nearby cells can release renin which affects reabsorption of sodium ions.

Getting quantitative

In each lined section below I have attempted to put in some figures about the processes occurring

Blood flow in context

The volume of blood in the human body is about 5 litres. Plasma is only 55% of the volume of blood.

The heart beats about 100,000 times in a day (24 hours) - giving a flow rate equivalent to 7000 litres per day.

In this time the kidneys receive 1440 litres of blood, so they process the body's blood 288 times a day.

Formation of glomerular filtrate

Bowman's Capsule enclosing the glomerulus bowmans (51K) A digitised and idealised image from Gray's Anatomy
The difference in diameter between the afferent and efferent arterioles means that blood slows down and blood pressure forces the lighter liquid fraction of the blood plasma to leak out from the capillaries of the glomerulus, which have small pores in their endothelium.

Surrounding the capillaries and forming the inner surface of the capsule is a basement membrane with small perforations, and this is supported by finger-like extensions of podocyte cells. These perforations allow only fairly small molecules to pass through - a process known as ultrafiltration.

The resulting liquid which is formed - glomerular filtrate - consists of Most of the useful substances are reabsorbed into the blood in the next sections and the waste substances become more concentrated as the filtrate passes onwards.

The following components are not usually removed from the blood in the glomerulus: What would be the significance of finding blood or protein in the urine?
> Probably indicates mechanical damage to the basement membrane and capillaries
Sketch of renal capsule and glomerulus Glomerular_Physiology (218K)
Modified from Wikimedia Commons, the free media repository

Glomerular filtration rate (GFR)

This is a test used to check how well the kidneys are working. It is sometimes calculated by measuring creatinine levels in the blood, or after injection of inulin, or even small doses of radioactive markers
Normal GFR varies according to age, sex, and body size; in young adults it is approximately 120 ml/min/1.73 m2 and it gradually declines with age.

These rather odd units refer to the rate of flow of blood into the kidney, which depends on body size, so it is calculated to match a standard body size - with 1.73 m2 of skin surface.

Glomerular filtrate is about 12% of the flow rate of blood into the kidneys.
This amounts to 172 litres over a 24 hour period.
About 99% of this is reabsorbed, so we produce about 1.7 litres of urine in this time.

Reabsorption of glucose and amino acids (with sodium ions and water) from the proximal convoluted tubule

As the glomerular filtrate passes out of the renal capsule it flows into the proximal convoluted tubule, which is lined with a single layer of cells.

These cells have different protein transporters and carriers on their inner (luminal) surface and their outer (apical) surface. This enables substances to pass out of the filtrate and into the cells lining the tubule, then onwards into the blood in the surrounding capillaries.

Glucose is moved into the lining cells by secondary active transport (ion-coupled transport). It then passes out by facilitated diffusion.

The main transport mechanism for glucose is a sodium (ion)-glucose cotransporter and the glucose entering the cells then passes out via glucose channels to re-enter the blood in the surrounding capillaries.

This movement is powered by the concentration gradient set up by an ATP-powered sodium-potassium ion pump (as found in other cells, such as nerve cells). This pumps sodium ions out of the cells into the interstitial space outside, whilst potassium ions move in the opposite direction.

Water also accompanies the glucose and sodium ions as solvent so it is also passively reabsorbed as a result of osmosis.

Normally, all the glucose in the filtrate is reabsorbed within the proximal convoluted tubule.

There are also transport proteins for amino acids (Na+/amino acid symporters) in these cell membranes, so 100% of amino acids are reabosrbed here too.

About two thirds of the salts (sodium and chloride ions, also potassium and phosphate) and two thirds of the water are also reabsorbed into the blood at this stage.

The fluid passing out from the proximal convoluted tubule has the same osmolarity as blood plasma.

In this account the term filtrate is not used from here onwards, as the composition of the fluid within the tubule has been modified.

Too much glucose to reabsorb

In diabetes mellitus the blood glucose concentration is uncontrolled and generally higher than the amount that can be reabsorbed in the primary convoluted tubule. Consequently some glucose remains in the fluid within the tubule and eventually leaves the body in the urine.
Reabsorption of glucose and sodium ions in the proximal convoluted tubule

proximal_cell (40K)

[components not shown to scale]
SGLT2 is a (Sodium ion) Glucose cotransporter (symporter)
[This is similar to the SGLT1 glucose transporter which is involved in the absorption of glucose into cells lining the ileum, but it imports single Na+ ions with each glucose molecule.]
GLUT2 is a glucose channel (carrier protein)
Na+/K+ ATPase is a sodium-potassium ion pump

What is the significance of the following features shown in the diagram?

microvilli on the inner surface?
> increase surface area for inward diffusion of glucose and Na+
mitochondria near to the outer surface?
> aerobic respiration to produce ATP for Na+/K+ATPase

These are not the only carrier proteins in these cell membranes.
Various channel proteins allow potassium and chloride ions to pass though the cell membrane and into the blood, as well as HCO3- ions passing into the blood and H+ into the lumen.

The rate of reabsorption of water and dissolved solutes (into the blood capillaries alongside the proximal convoluted tubule) is about 115 litres per 24 hours.

The osmolarity of fluid leaving the proximal convoluted tubule (flow rate now down to about 57 litres per 24 hours) is practically identical to blood plasma, about 300 mOsm/L.

It all gets concentrated outside of the loop of Henle

The loop of Henle acts as a countercurrent multiplier

loopfigures (40K)
Leading down in the medulla there is a distinct difference in osmolarity between the two limbs and a gradient of sodium ions in the medulla

In the descending limb of the loop of Henle water passes out of the fluid inside the tubule and into the surrounding interstitial fluid, which is increasingly "salty" in the lower regions of the medula.

This movement of water is caused because cells lining the ascending limb alongside actively transport sodium and chloride ions out into the interstitial fluid between them.

As it passes down the descending limb, the water content of the tubule fluid is greatly reduced, in proportion to the osmolarity of the interstitial fluid.

Then as it passes up the ascending limb, the tubule fluid's sodium chloride concentration also falls because these ions are being pumped out, so that the fluid inside the loop of Henle is both greatly reduced in volume, and hypotonic to blood.
The membrane on this side is impermeable to water, so water is not reabsorbed from the fluid outside.

The net result of the movement of sodium and chloride ions is to create a tonicity gradient or gradient of sodium ions in the medulla of the kidney.

Effect of chemical inhibitors

Various drugs are used to treat high blood pressure.

So-called loop diuretics, e.g. Furosemide, act by inhibiting the Na-K-Cl cotransporter in the loop of Henle, by binding to the chloride transport channel, thus causing sodium, chloride, and potassium ions to remain in the tubule and eventually pass out in urine. In so doing they causes an increase in the volume of urine produced - diuresis.

They cause a decrease in blood pressure by lowering the volume of blood in the body.

ascendingloop (3K)
Embedded in the inner membrane of cells lining the ascending limb is a protein that aids in the secondary active transport of sodium, potassium, and chloride ions. The Na-K-Cl cotransporter (NKCC) actually moves sodium ions, potassium ions and chloride ions in the same direction, so it is a symporter. Movement of Na+, K+ and Cl- are in the proportion 1:1:2 and this does not set up a membrane potential as occurs in nerve cells.

On the other side of the cell there is a sodium-potassium ion pump Na+/K+ ATPase releasing sodium ions into the interstitial fluid.

Running alongside the loop of Henle are blood capillaries, and their lining cells and enclosed blood cells are also subject to osmotic influences as they descend into the medulla. Obviously these supply the tubule lining cells with oxygen and glucose which are necessary for cells to respire and support the active transport processes. And as the blood flows back up from the medulla, water flows back into the blood and reverses the effects of 'saltiness'.

The gradient of sodium ions takes the osmolarity of interstitial fluid to about 1200 mOsm/L at the tip of the pyramid (at the bottom in most diagrams). As the the fluid inside the tubule equilibrates with the interstitial fluid, loss of water causes the flow rate to decrease (by a factor of 4?).

Then in the ascending limb the tubule fluid loses sodium and other ions and so its osmolarity decreases, moving from about 1200 mOsm/L to about 100 mOsm/L, which is its lowest value. This loss of solutes causes the flow rate to decrease even more.

The osmolarity of fluid leaving the loop of Henle is now below that of blood plasma. The flow rate is now quite low - perhaps down to about 1-2 litres per 24 hours.

The last movement of ions in the distal convoluted tubule

In this region, the concentration of sodium and chloride ions in the blood may be regulated, as well as potassium and calcium ions. This is a result of other hormones initiating different active transport processes.

The pH of blood may also be regulated by moving H+ ions into the tubule and HCO3- ions into the bloodstream.
As a result the urine may be made more acidic and the blood more alkaline - its pH is 7.4.
Similar mechanisms (cotransporters powered by sodium/potassium ion ATPase pumps) function within the distal convoluted tubule, but they are controlled by other hormones.

distalcell (68K)
Within the cell CO2 and H2O form carbonic acid H2CO3 which is speedily hydrolysed by carbonic anhydrase enzyme into hydrogencarbonate (HCO3-) and hydrogen ions (H+).

Blood pH is regulated by the absorption of HCO3-) ions into the bloodstream, raising the pH, and secretion of H+ into the tubule fluid, to be excreted in urine and lowering the pH.

The final adjustment can be made to sodium ion concentration, with hormone-controlled reabsorption if necessary. Calcium ions may be transported into the blood, and potassium ions may pass into the tubule fluid.

Hormones involved

Aldosterone, a steroid hormone produced in the cortex of the adrenal gland, may increase the reabsorption of sodium and chloride ions and secretion of potassium ions into the tubular fluid. The secretion of aldosterone is controlled by angiotensin (I), produced in the liver, and converted into its active form angiotensin (II) by renin which is produced in the juxtaglomerular cells in the kidneys, in response to reduced renal blood flow.

As a result more urine is produced, and its concentration is decreased.

Parathyroid hormone PTH causes reabsorption of calcium ions.

Fine-tuning the reabsorption of water under the control of ADH

At this stage, the fluid inside the tubule is quite watery as a result of ions being actively transported away.

In the (short) final sections of the nephron, mainly the distal convoluted tubule and collecting ducts, water may leave the tubule and pass into the blood, if it is required to restore the blood's water potential (in the rest of the body) by diluting it, so the water potential is made 'less negative'.

This is caused by an increase in the permeability of the cell membranes of the tubules in response to the hormone ADH released from the pituitary gland, allowing water to move out by osmosis.

The cell membrane is made significantly more permeable to water as a result of the incorporation of the channel protein aquaporin into the cell membrane so water moves out down a concentration gradient by facilitated diffusion.

As a result less urine is produced, and its concentration is increased.

And the water potential of circulating blood is restored to its normal value.

When reabsorption of water does not work

The condition Diabetes insipidus is caused by problems with the hormonal control of water reabsorption in the final parts of the kidney tubule.

This change in the functioning of the kidneys may be a genetic condition or a result of damage or disease.

Symptoms include thirst and excessive production of very dilute urine - perhaps 20 litres per day, instead of the usual 1-2 litres. There are a number of other consequences , such as frequent need to get up to urinate during the night.

There are different forms of diabetes insipidus:
Cranial diabetes insipidus. is caused by events within the brain, so that the hypothalamus does not produce any ADH (and possibly other hormones)
Nephrogenic diabetes insipidus is caused by problems in the kidneys, such as lack of receptors for ADH, or non-production of aquaporin.

Lack of receptors for ADH as an inherited condition is usually caused by a mutant recessive allele carried on the X chromosome.

Which sex is more likely to be affected by this condition?
> male
Give a reason for this.
> Only one copy of mutant allele causes condition/cannot be heterozygous as male sex chromosomes are XY
In females both copies would have to be mutant/ mutant may be masked by single normal allele because females are XX

Antidiuretic hormone binds with receptors in the membrane of cells of the distal convoluted tubule and collecting ducts. This receptor - vasopressin receptor 2 (V2R) - is a 'G-protein-coupled receptor', which stimulates the enzyme adenylate cyclase to catalyse the conversion of ATP to 3',5'-cyclic AMP.
Cyclic AMP acts as a second messenger, activating a signalling pathway that causes vesicles containing aquaporin 2 to fuse with the plasma membrane.

More Aquaporin, more water reabsorbed

Aquaporins-01 (483K)
From 26.2 Water Balance by Rice University

There are different versions of the water channel protein aquaporin in the kidney tubules.

AQP2 can only be found in the lining cells of the connecting tubule and collecting duct. It is normally stored in vacuoles, but under the influence of antidiuretic hormone it is brought into action and inserted into the inner surface of the cells, forming a very efficient water channel for the facilitated diffusion of water.

AQP3 and AQP4 are both present in the outer membrane of collecting duct cells. They are always present and provide the exit pathway into the bloodstream.
Double feedback loops for homeostatic control of blood water potential

ADHloop (44K)

Once again, we see that the possession of separate mechanisms involving negative feedback controls departures in different directions from the original state, giving a greater degree of control.

Other related topics on this site

(also accessible from the drop-down menu above)
Similar level
Control of blood glucose concentration
Inorganic ions
Transport across cell membranes

Web references

Water Balance part of Chapter 26. Fluid, Electrolyte, and Acid-Base Balance
26.3 Electrolyte Balance Fluid, Electrolyte, and Acid-Base Balance
Exercise-Associated Hyponatremia
Salt reduction
Contribution of Water from Food and Fluids to Total Water Intake: Analysis of a French and UK Population Surveys

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