81. States of decreased extracellular volume, and their consequences

Last updated on May 25, 2019 at 19:34

Before we begin

Extracellular space = ECS = Intravascular space + interstitial space

Intracellular space = ICS

Intravascular space = IVS

We must know the difference between osmolarity and tonicity.

Osmolarity is the measure of how many osmoles, i.e. dissolved particles are in a solution. If solution A contains more salt than solution B will, all other things being equal, solution A have higher osmolarity than solution B.

Tonicity is the measure of how different the osmolarity of two solutions are. If solution A has higher osmolarity than solution B is solution A hypertonic compared to solution B.

When we talk about tonicity in the body do we usually mean the difference in osmolarity between the intracellular and extracellular space. However, this is only true for substances that can’t pass freely through cell membranes. For example, if the glucose concentration of the blood increases will it be hypertonic, because glucose can’t freely cross cell membranes. Because it can’t do that will water flow from the ICS into the ECS. It would not work for ethanol, urea, methanol or other substances that freely diffuse across cell membranes, because that wouldn’t cause a water flow.

Hypertonicity is the state where the osmolarity of the extracellular space is higher than the osmolarity of the intracellular space. This causes fluid to move from the cells and out, causing cells to shrink.

Hypotonicity is where the osmolarity of the intracellular space is higher. This causes water to enter the cells, causing them to swell.

Fluid spaces in the body

Around 60% of the body weight in a normal person is water. Of this is two thirds in the intracellular and one third in the extracellular space. An easy way to remember this is the 60-40-20 rule. The body is 60% water, 40% of the body weight is water in the intracellular space and 20% of the body weight is water in the extracellular space.

The composition of the compartments differs as well. In the ECS is sodium the dominant cation while in the ICS is potassium the dominant cation. In the ECS is chloride the dominant anion while in the ICS are phosphate and protein anions dominant. pH is slightly lower in the ICS, around 7.2.

The osmolarity in all fluid spaces is the same though. Regulation of normal volume always has more priority than regulating the osmolarity, pH or K+ balance

The ICS doesn’t really have the capacity to decrease or increase in size. When we talk about hypo or hypervolaemia we mean the ECS. The same goes for tonicity – it mostly depends on the osmolarity of the ECS.

Considering we can have hypo-, normo-, and hypervolaemia and hypo-, normo- and hypertonicity simultaneously do we have 9 possible combinations, where just one of them is normal:

Extracellular volume
Increased Hypotonic hypervolaemia Normotonic hypervolaemia Hypertonic hypervolaemia
Normal Hypotonic normovolaemia Normotonic normovolaemia Hypertonic normovolaemia
Decreased Hypotonic hypovolaemia Normotonic hypovolaemia Hypertonic hypovolaemia
Decreased Normal Increased Tonicity

Osmo and volume regulation are tightly interconnected, as they depend on each other. However, we’ll try to examine them separately.

Regulation of volume

Despite what may seem logical is volume majorly regulated by Na+ intake and salt excretion. This is because water follows Na+. This means that when you are hypovolaemic will you not be (primarily) thirsty, you’ll have salt craving (although you should probably drink water also). RAAS will also be activated to retain more salt. When you are hypervolaemic will there be less RAAS activation and therefore less aldosterone, causing Na+ excretion where water will follow. Natriuretic factors like atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) will also be activated in hypervolaemia, causing Na+ excretion.

The easiest ECS to regulate is the intravascular volume, as it is here the majority of salt is. If the ECS increases or decreases in volume will that change quickly transfer to the interstitial space as well, because they are interconnected.

In severe hypovolaemia will ADH also be activated, causing water retention without Na+ retention. This decreases the osmolarity of the ECS, causing hypotonicity. A hypotonic normovolaemia occurs. However, as we talked about, having normal volume is more important for the body than to have isotonicity.

The kidneys are good at their job, so if you suddenly increase you salt intake will they soon increase the salt excretion, so that the Na+ level in the blood is just a little elevated. If you continue with this increased salt intake will the kidneys continue to excrete more. This means that the kidneys will always try to match the salt intake to prevent the Na+ level from increasing too much.

States of decreased extracellular volume (hypovolaemia)

Exsiccosis means a salt and water loss from not just the intravascular space but also the interstitial space. Dehydration usually means just a simple water loss, without salt loss. When water without salt is lost must osmolarity go up, meaning that the ECS will become hypertonic and water will flow out from cells.

Depending on the cause of water loss do we have three possibilities:

  1. Salt is simultaneously lost and more salt is lost than water, so hypotonicity occurs
  2. Salt is simultaneously lost and salt and water are both lost in equal amount, so normotonicity occurs
  3. Water is lost without salt loss, or salt loss is smaller than the water loss. Hypertonicity occurs.

It’s important to note that aldosterone causes salt and water retention in equal amounts, while ADH causes just water retention. Aldosterone therefore doesn’t change the tonicity, but increased ADH causes hypotonicity.

Based on these three possibilities must we separate the causes for hypovolaemia into three:

Hypotonic hypovolaemia (more salt is lost than water) Normotonic hypovolaemia (salt and water loss are equal) Hypertonic hypovolaemia (more water is lost than salt)
  • Addison disease
  • Salt-losing kidney
  • RTA IV
  • Ileus
  • Cystic fibrosis
  • Burns
  • Blood loss
  • Vomiting
  • Diarrhoea
  • Asthenuric polyuria
  • Decreased water intake
  • Diabetes insipidus
  • Osmotic diuresis
  • Sweating
  • Polyuric phase of renal disease
  • Very dry environment

Hypotonic hypovolaemia:

Addison’s disease is characterized by low aldosterone. To compensate for this will the pituitary release more ADH. The urine will contain less water, which makes the body hypotonic.

Renal tubular acidosis IV is characterised by decreased effect of aldosterone and therefore follows the same mechanism.

Salt-losing kidney occurs when the kidney loses more salt than water, like in acute tubular necrosis, where the damaged tubules passively reabsorb a lot of fluid but can’t actively reabsorb salt.

Cystic fibrosis is characterised by chloride channel deficiency. Problems with chloride channels makes them lose more salt than normal in diarrhoea and sweating, probably because salt reabsorption is deficient.

Normotonic hypovolaemia:

Severe burns remove the upper layers of the skin, which causes increased skin evaporation from the plasma.

Blood loss depletes the body of salt and water in equal amounts. Same goes for vomiting and diarrhoea.

Asthenuric polyuria, or isosthenuric polyuria means that the kidneys can’t concentrate the ultrafiltrate, so the urine has equal osmolarity as the ultrafiltrate, which again has equal osmolarity as the plasma.

Hypertonic hypovolaemia:

Decreased water intake but normal salt intake means that the osmolarity of the ECS increases.

Diabetes insipidus is a condition where ADH is deficient, meaning that the body can’t retain as much water, so it becomes hypertonic.

In osmotic diuresis will osmotically active substances in the filtrate (mostly glucose in DM) cause increased water excretion.

Interestingly is sweat hypotonic, meaning it has lower osmolarity than the serum. When you sweat a lot will you therefore lose more water than salt, causing hypertonicity.

Consequences of hypovolaemia
  • Decreased turgor of the skin
  • Decreased blood pressure
  • Increased orthostatic hypotension
  • Increased blood viscosity
  • Poor tissue perfusion
  • Hypovolaemic shock

All depending on the severity, of course.

Infants and elderly have lesser capacity to compensate for hypovolaemia, as they have limited ability to move fluid from the interstitium into the vessels. Also, the feeling of thirst is smaller in elderly, so they’re more prone to forget to drink.

Compensation of hypovolaemia

Where possible will RAAS be activated and aldosterone will cause salt and water retention. In severe hypovolaemia will ADH also be activated, where possible (i.e. not in diabetes insipidus).


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80. Disorders of potassium balance. Hypo- and hyperkalaemia

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82. States of elevated extracellular volume. Causes, mechanisms and consequences

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