Body Fluid Compartments

The areas covered in this plenary are

Curiously enough, I'm going to start with the "point" and work backwards

.....if you haven't previously studied Biology, you may find the following useful

Although not, stricly speaking, within the remit of a plenary on "body" fluid compartments, it is probably worth mentioning that some of the most interesting current research is on intracellular compartments. One of the biggest differences between procaryotes (bacteria) and eucaryotes (animal and plant cells) is the presence of a nucleus where the "self-replicating molecules" (DNA) live. Straightaway we have an additional compartment in the cell. Even more interesting is the fact that, in some cell types at least, different areas of the cytoplasm behave as different compartments. Salivary gland acinar cells (for example) have a secretory pole from which secretion occurs and a basolateral pole, where other things happen. Homeostatic regulation of Ca2+ signalling at one end of the cell can be quite different from that of the other.
And now back to the main program.......

From single cell to multicellular organism

In the beginning...(again)

section through a flatwormAlthough it might be argued that bacteria represent the most successful cellular lifeform on the planet, because there are more of them then anything else, being a multicellular organism does seem to have some things going for it. The simplest possible multicellular organism is a sponge. A sponge is a collection of identical cells that exist as a colony. Sponges are even more dull than bacteria. Flatworms (Platyhelminthes) have a slightly more exciting body-plan, where the cells on the outside have a different function (protective and absorptive), from those on the inside (mainly reproductive). Ever wonder why a flatworm is flat? (or is it just me). Flatworms are flat in order to provide the shortest possible diffusion pathways for oxygen and carbon dioxide between the surface of the worm and its interior. Flatworms need to be flat because they do not have a circulatory system. Notwithstanding these deficiencies, flatworms are the simplest creatures to have an more than one body fluid compartment. They have two; an interstitial (in-the-spaces) compartment and an intracellular compartment. In short the outer layer of the flatworm creates a comfortable internal environment for all the other cells to live in. Homeostasis may now occur at both the level of the single cell and at the level of the whole organism.

This may be nice and cosy, but it does mean that you have to be flat. Any non-flat body plan puts the innermost cells too far away from the outside to survive by diffusion alone.

Every metazoan (multi-celled organism) more advanced than a flatworm has discovered that the way to avoid being flat is to have a circulatory system that can reach the body parts that diffusion cannot. Once past this hurdle, all sorts of specialisation amongst the cells that comprise an organism becomes possible. The digestive system is a way of extending the surface area for digestion whilst simultaneously protecting it by internalising it, thus the same cells don't have to try and combine protective and digestive functions. The lungs are essentially the result of the same principle applied to the problem of gaseous exchange. The liver, the brain, the muscles etc. etc. etc. have all evolved to play their own part in the homeostasis of the whole organism. The part of the body that has charge of maintaining the ionic composition of the organism, a task analogous to that of the plasma membrane in a single cell, is the kidney.

Where is all the water

red dwarfA 70 kg man (the figures are slightly different for women) contains about 40-45 litres of water.... Which means that If all the water were removed from a human body some 30 kg of assorted salts would remain. Despite the impression given by Star Trek or Red Dwarf (remember them?) where dried people are represented by a tiny pile of salt crystals, 30 kg is a lot of material. Imagine the mess you could make with 15 bags of sugar....... sugar

In the human body, about 60% of the fluid is in the intracellular compartment. Any fluid not inside a cell therefore comprises the extracellular compartment. The extracellular compartment may be divided into an interstitial compartment and a circulating compartment (the blood plasma and the lymph fluid). The distribution of fluid between the compartments is approximately as follows.

Total 40l Intracellular 24l  
  Extracellular 16l Interstitial 12l
    Plasma 3l
    Lymph 1l
The overall osmolarity of all three compartments is identical at about 300 mOsmol/l

So, the point of the circulating compartment (the blood and the lymph) is to circulate. Most especially to take O2 and glucose to the cells or the organs and to remove CO2 and other waste products.

The point of the intracellular compartment is to create a happy homeostatically regulated environment for cellular processes.

.... and the point of the interstitial compartment is to fill the gaps between the cells and to allow communication between the circulating and intracellular compartments (otherwise the whole thing would be pointless)

How do we know the volume of each of these compartments? We use the Indicator Dilution technique (obviously).

Capillaries and Starling forces

To make the whole circulatory system work, you need the heart and major blood vessels to pump blood around the system. There must also be movement of fluid, and all the things dissolved in it, from the circulatory system into the interstitial compartment so that the dissolved contents come into direct content with the cells. There must also be fluid movement from the tissues back into the blood vessels or else your organs would explode (actually, I'm not sure if they would explode, you would get oedema (swollen; fluid-in-the-tissues). In any case, not very healthy or useful.)

Major blood vessels are water-tight, fluid cannot leak out of an artery, but the teeny-tiny capillaries that link arteriole to venule and surround the tissues are not. Capillaries are a bit like a leaky hosepipe - as water passes through the pipe, some of it squirts out through the holes. The capillaries are more clever than a leaky hosepipe because they also manage to recover (most of) the water that escaped through the holes. The bright lad who figured out that Capillary Osmotic Pressure c) was the key to circulation from capillaries to the tissues and back was Ernest Starling.

The way it works is really very simple. Fluid moves from high pressure to low pressure. Capillary Hydrostatic Pressure (Pc) and Capillary Osmotic Pressure act in opposite directions across the capillary wall. Capillary Hydrostatic Pressure forces fluid out of the capillary, Capillary Osmotic Pressure draws it back in. Capillary Osmotic Pressure doesn't change along the length of a capillary but Capillary Hydrostatic pressure declines from about 30 mmHg to 15 mmHg. Therefore, Capillary Osmotic Pressure is less that Capillary Hydrostatic Presssure at the arterial end of the capillary and fluid moves out of the capillary. It moves back in at the venous end of the capillary because Capillary Hydrostatic Pressure is now smaller than Capillary Osmotic Pressure. The soluble contents of blood plasma filter through the capillary walls along with the fluid into the interstitial fluid bathing the cells. Nutrients feed the cells and waste products are returned to the capillaries at the venous end. Oxygen and CO2 being lipid soluble, can move by diffusion as well as by convection.

Starling's forcesThe balance of hydrostatic and osmotic forces causing movement out and into the capillaries are known as Starling's forces. The most simple formulation of the Starling equation is that net pressure is Capillary Hydrostatic Pressure and Capillary Osmotic Pressure (net pressure = Pc - πc). Notice that the net force is positive (fluid moves out) at the arterial end of the capillary and negative (fluid moves in) at the venous end. The pressures aren't quite equal and opposite, the net pressure for efflux from the capillary (8 mmHg) is slightly greater than that for influx (7 mmHg). Therefore, more fluid leaves than is recovered. The lymph vessels mop up the extra fluid and return it to the circulation.

If you think that this is just too simple to be true in a biological system then you are exactly right. Real life is more complicated in several ways but, the principle doesn't change. Get the idea of fluid movement as a consequence of the balance between hydrostatic and osmotic pressures into your head first and then look for the complications.

Complications

In the first place, there are four Starling's forces (not two)......

In addition to Capillary hydrostatic and osmotic pressures, there are also interstitial hydrostatic (Pi) and osmotic (πi) pressures. One reason that we can get sensible answers by ignoring then is that they are both small to negligible compared to the capillary pressures. Another reason is that they don't change much (if at all) along the length of the capillary. Notice that interstitial hydrostatic pressure is negative e.g. less than ambient or atmospheric.

Starling's forces

To complicate matters a little more, osmotic pressure should be corrected for the reflection coefficient (σ), which takes into account the fact that some proteins can get through some capillaries. If the capillary is really, really tight (like the gomerular capillaries in the kidney) then the reflection coefficient will be 1. Some capillaries (for example in the liver) allow (small) proteins fairly free passage and so the reflection coefficient of these capillaries is (much) less than 1.

Net pressure is therefore given by (Pc - Pi) - σ (πc + πi)

Notice that I have given a different set of values in my two examples. Which are the correct values? Neither or both of course. There is no such thing as a "typical" capillary. The values of all the pressures will vary from organ to organ and within any organ depending on time of day, activity, phase of the moon and so on and so forth. It isn't even true that there is always a circulation of fluid from the capillaries and back. In the glomerular capillaries, fluid moves from capillaries to urine.... but not back again. In the lungs, little or no fluid moves into the alveoli (for obvious reasons). The point is that the values are fine tuned for each and every capillary bed. Furthermore, the values will change depending on whether the organ in question is busy or not. How could there be "typical values"? Anyway, don't obsess about values, it is much more important to understand the principles.

There is one last thing. How much fluid moves depends both on the net pressure and on the Capillary Filtration Coefficient (Kf). The Capillary Filtration coefficient is simply a measure of how leaky a capillary is. Very leaky capillaries have high filtration coefficients and therefore move lots of water. Less leaky capillaries have lower filtration coefficients and (for a given net pressure) allow less water through.

The final, complete version of Starling's equation for fluid flow (J) out or into a capillary is therefore:

J = Kf ([Pc - Pi] - σ [πc + πi])

A handy equation for many an occasion.

Capillary Permeability

Capillaries may be broadly divided into three types based on their leakiness.....which is itself determined by the size of the holes in the capillary wall.

continuous capillary Continuous capillaries have a close connection between adjacent cells and will permit only small molecules < 10nm in diameter to cross. Continuous capillaries surround muscle, skin lungs, adipose tissue CNS, retina and mammary glands.
fenestrated capillaryFenestrated capillaries contain fenestrations or "windows" that offer easy passage to larger molecules (10-100nm) and are found around the kidneys, pancreas, gallbladder and intestine.
discontinuous capillaryDiscontinuous have wide gaps between the cells and will allow practically anything (even cells) across. Discontinuous capillaries surround the liver, spleen, ovaries and some endocrine glands.

All capillaries are composed of a layer of endothelial cells surrounded by a basement membrane. To cross from the plasma to the cells or vice versa, substances must either cross both membranes of the endothelial cells or travel between the cells and then cross the basement membrane.

Don't forget to look at Defense of body osmolarity