The Renin-Angiotensin-Aldosterone System Content from the guide to life, the universe and everything

The Renin-Angiotensin-Aldosterone System

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Hormones control a great deal within our bodies and, indeed, many determine several aspects of our lives - a case in point is the particularly choppy period known as adolescence, which never ceases to make parents' lives a great deal more interesting, and teenagers' lives a great deal more turbulent.

They also control many aspects that we take for granted, such as the fight-or-flight response, and perhaps appetite. One very important aspect which is in some part controlled by hormones, is blood pressure.

A Situation

When we are exercising when it is very hot, the body reacts to a possible overheating by sweating. In this process, water and a few salts are secreted from sweat glands to cover the surface of the skin. The heat causes this thin layer of sweat to evaporate, and heat to be lost more efficiently from the body.

The advantage of this is that you don't over-heat. The disadvantage is that you lose water. If you don't replenish it by drinking, this constant loss of water will leave you dehydrated, and consequently, your blood pressure will drop. It would continue to drop, if it were not for an adaptation of the body.

The Nervous Reaction

Of course, the body has to keep a close eye on important aspects of bodily function such as blood pressure, and it does this primarily via the nervous system. Signals communicated from this system are quick, and the reaction to stimuli is just as quick, as anyone who has stuck their hand on a hot stove without realising it may know.

The nervous system innervates large blood vessels such as the carotid artery and the vena cava - the largest vein in the body, the anatomy of which is worth going into here.

There are two parts to this vein; the Superior Vena Cava, which carries blood from the brain, neck, upper chest and arms to the right side of the heart, and the Inferior Vena Cava, which carries blood from the rest of the body to the right side of the heart.

These vessels are wired up with stretch receptors. Consequently, any decrease in blood volume either through loss of fluid or just by standing up is detected quickly, and prompt action can be taken. Standing up gives the characteristic 'headrush' effect; which is also worth explaining.

Think of the hydrostatic pressures when you lie down - they are fairly evenly distributed. Now when you stand up, the effect of gravity is such that there is relatively less blood in your upper body and head, and relatively more in your lower parts. There would be a relative drop in blood pressure in your head, and a relative increase in your feet. This is partly why you may feel a bit of a 'headrush' when you get up first thing in the morning. Of course, this now means that the word 'headrush' is a wholly inaccurate misnomer, however its continued use may be due to the familiarity rather than the accuracy of the term. 'Head-drain' doesn't have quite the same ring to it.

Nerves also innervate other arteries within the body. These specifically wire the muscle layer within the artery wall, and if there is a drop in blood pressure then signals are sent for the muscle to contract. This results in the diameter of the artery decreasing and, by virtue of the close relationship between area and pressure, the decrease in area by this vasoconstriction leads to an overall increase in blood pressure back toward the normal range.

The nervous effect, however, is temporary. If the drop in blood pressure is longer standing, then a longer-term solution is required.

Enter our hormones.

In the Beginning...

The first organs to detect changes in blood pressure are our kidneys. This may seem a little strange, as it would make sense for the brain to detect such changes. Actually, there is a very good anatomical reason for this. Firstly, as the head is above the heart, by virtue of gravity the blood pressure within the skull is comparatively lower than downstream. Secondly, the kidneys need to filter the entire volume of our blood, and very quickly. Hence, blood enters our kidneys at very high pressures; almost directly from the aorta - the largest artery in the body, and the one that carries our blood as soon as it comes out of the heart. So any changes in blood pressure are first detected in the kidneys.

If the changes are too large, or that which cannot be overcome by the nervous reaction, combined with the vasoconstriction this then prompts our kidneys to release into the blood a substance called Renin, named thus as it is secreted by our major renal organs.

An Expected Meeting

Renin is a small peptide - a small string of amino acids. It is carried along in the blood, and just as all blood is filtered in the kidney, all blood is put through the customs control centre of the body, the mysterious liver.

Quite on its own, the liver also detects this drop in blood pressure, and begins making the necessary preparations. The major change it makes is to a large protein called Angiotensinogen; cutting it up to produce another protein called Angiotensin I. The Renin comes to meet the liver, and stimulates it to keep cutting and produce more Angiotensin I.

The Baton is Passed on...

So the burden lies with our new protein, Angiotensin I. This drifts along in the blood, until it passes through that other organ through which all blood must pass - the lungs.

From the lungs is released another enzyme, Angiotensin Converting Enzyme, or ACE for short, and this cuts Angiotensin I into the far more potent Angiotensin II. It is this hormone which really starts to shake things up.

Angiotensin II

The more potent son of Angiotensin I, Angiotensin II is the most potent vasoconstrictor in the body. Whereas the nervous reaction is localised, the effects of a hormone such as Angiotensin II are very general. Vasoconstriction happens everywhere, bringing the blood pressure back towards normal.

If the diameter of our blood vessels were the only aspect of blood pressure, then this would be sufficient. However, this is ignoring one simple fact. Everybody loses water through urination.

A Return to Familiar Ground...

So, back to the kidneys. When blood is filtered through the kidneys it filters out all the big bits of our blood, such as large proteins, cells and the like. Small things like glucose, water and electrolytes such as sodium pass through. It is then when the water enters the nephron - the major fine filtering tool within the kidneys.

The human body doesn't want to lose water, but it has to get rid of the excess. So somehow, the body needs to keep as much water back as possible whilst still excreting the excess water. A convoluted solution to this has therefore been devised. Have this diagram of a nephron at hand, as the explanation below will not make much sense without it.

The Loop of Henlé

As the fluid passes from the proximal convoluted tubule, it enters the Loop of Henlé. The surrounding tissue is relatively low in sodium concentration compared to within the descending arm, and the walls of this arm are permeable only to sodium ions. So as the fluid runs into the Loop, water is retained within and sodium ions, by virtue of the difference in concentration between the tissue and within the Loop, diffuse out. This makes the surrounding tissue more concentrated in sodium ions1, and the fluid within the Loop less so, making it a hypertonic fluid.

Now, as the fluid does a U-turn, and enters the ascending arm of the Loop, the surrounding tissue is relatively high in sodium ion concentration. However, the ascending arm is not permeable to sodium ions, but it is permeable to water. So by the process of osmosis, most of the water is reabsorbed.

If more water is to be reabsorbed to return blood pressure to the normal range, then it makes sense to increase the sodium ion concentration in the surrounding tissues. This is the job of the final hormone in the system.

The Final Leg

Angiotensin II has another effect on the body, and that is to stimulate a gland known as the Adrenal Gland. These sit on the top of the kidneys, and secrete various hormones from different areas within. In this case, Angiotensin II stimulates an area of the Adrenal gland known as the zona glomerulosa - have a look at this diagram of the Adrenal Glands to see where the layers are - to secrete the steroid hormoneAldosterone. This hormone encourages sodium to be secreted into, and retained in, the tissues, and thus more water to be reabsorbed into the body.

With all the effects combined, this leads to the return of our blood pressure back to normal limits, and the system moves to the background, ready for the next time it's needed.

Kicking In

As mentioned before, the nervous reaction to the drop in blood pressure is quick, with the effect happening within milliseconds. So how long does the Renin-Angiotensin-Aldosterone System take to work?

It all depends on which part of the system you are talking about. The Renin-Angiotensin part may take seconds to minutes to kick in, whereas the Aldosterone part, because it is a steroid hormone, may take days to weeks to work. In effect, the nervous reaction covers the 'here and now', the Renin-Angiotensin segment covers the short-term, and the Aldosterone segment covers the much longer term drop in blood pressure. This is why you might find that in much warmer climes, if you are not drinking enough water, you don't urinate as frequently.

In Conclusion

The Renin-Angiotensin-Aldosterone System, despite having a rather cumbersome name, is probably one of the most elegant methods of a tightly controlled feedback system. Certainly, it is an important maintenance tool for blood pressure, and one of the best examples of homeostatic control.

1Additional concentration maintenance is provided by the cells within the surrounding tissue, which take it upon themselves to secrete sodium.

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