TAMARA DI TELLA PILATES & TANGO PILATES
SCIENCE

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The nefron is composed by a glomerular portion and a tubular portion. Where is the nefron? It is inside the Malpighi pyramids. In the middle there is an interstice, a contention structure.  Nefrons present a glomerular and a tubular portion (scheme).
The last part of the tubular portion of the nefron end in what are called calyxes. Every calyx ends in the renal pelvis. And what comes out from there is the urethral which ends in the bladder, out of the bladder comes the urethra.  Blood then comes through the renal artery and enters the kidney, covering the renal pelvis. At a pelvis level it divides into branches, forming arches until it reaches the glomerulus.  Inside the glomerulus filtration is produced using the artery-capillary-vein scheme.  Water, ions and small molecules will pass through.  These substances will pass through a tubular portion of the kidney and there two processes will take place: secretion and re-absorption.

There are then three steps: filtration secretion and re-absorption.

Filtration: It is produced in one glomerular part of the nefron.  It is the passage of the glomerular capillary (blood) to the glomerulus.
Re-absorption:  it takes place in the tubular portion of the nefron. It is the passage of the tubule to the per-tubular artery. Within the kidney’s tubular portion, a part of the filtered elements “regrets” the process. It re-absorbs and returns to the body.  Re-absorption is what passes from the tubule to the organism or from the tubule to the per-tubular space; it returns to the blood, it returns to the body. It will return to some per-tubular arteries. It is always an exchange between the nefron and the blood.

Secretion: inside the tubular portion of the nefron. This is what I want to eliminate once again. It is the passage from the pre-tubular artery to the tubule.
It sounds ridiculous, doesn’t it? I filter substances, sodium for example.  It filters an enormous amount of sodium, it reabsorbs during the passage through the tubules and sodium is secreted once and once again in that tract. Why does exist so many comes and goes during this process? 

Inside the body this happens all the time, very often in every system. Why is so much energy spent in making and unmaking all the time? These are very important processes within the body. Since they are important they have to be regulated. Sodium’s cc is so important that the body spends lots of energy filtering, re-absorbing and returning to secrete that sodium.

What is left in the tubule will direct to the calyxes, and then into the pelvis.  At this level, what finally reached the sector is urine, already formed. It passes into the ureter, bladder (a contention, storage unit). When certain levels are reached the bladder signals the brain “you have to pee”, and when the bladder valve opens, that liquid enters the urethra. 
Let us analyze the glomerulus in detail.  We had said that arteries that reach the glomerulus will be branches of the renal arteries. At this level it will form once again an artery-capillary-vein system which will receive a special denomination. This artery is called afferent arteriole. This capillary is called glomerullar capillary since it borders the glomerulus.  And the vein is not called vein. It is denominated efferent arteriole. Is it a vein or not?
 
In reality it is not called vein since it does not allow any gaseous exchange. Therefore since it will not contain any venous blood, there will not be any oxygen exchange. However, the concept is still the same. An artery arrives, there is a capillary, and some different element, without a former substance just comes out. A filtration process then takes place (water, ions, small molecules), what is left?  Cells and proteins are the only non-filtered elements since they are large and complex.

 Renal Blood Flow

It is the amount of blood that reaches the kidney. It constitutes some 20% of net volume (let us also remember the amount of blood that the heart expels per minute).

The Kidney is a highly irrigated tissue since filtering of the body will take place there.
Renal Plasmatic Flow: It is a value which might attract much more our interest since is a part of the renal blood flow. Another value is the amount of plasma which reaches the kidney per second. Up to now we are only considering the plasma.

How much it enters to produce filtration. Glomerular Filtration Volume is how much blood filtrates into the glomerulus; and the filtration fraction. It is a relationship, equal to the glomerular filtration volume and to the renal plasmatic flow. It is 20%, which means that this is the percentage of the plasma which is filtered.

The same way that before we put water, oxygen and blood in contact, this time we are putting blood into contact with the glomerulus and limiting the amount of substance that passes through. This is due to a process denominated filtration. Filtration fraction is the glomerular filtration volume divided by renal plasmatic volume. In other words, how much of the incoming substance is filtered (20%).

Proteins are not filtered. We have then to consider two types of pressure: hydrostatic and oncotic. The first one is given by the water column, and the second by the proteins, it is given by the attraction produced by proteins.  At the afferent arteriole level, concentration of proteins will be higher. We shall remember that we are always speaking of relative values. Up to his point we do not find any synthesized proteins, but water happened to be extracted, thus raising the protein concentration. Their influence is oldstronger and the oncotic pressure will also be higher as opposed to hydrostatic pressure which will lower as a consequence of the loss of water. 

If we analyze these forces within the capillary they are the ones which will carry the filtration process, since this process is the result between these two forces’ relationship. No proteins reach the glomerulus, therefore the oncotic pressure within the glomerulus equals zero. On the opposite hand, there will be a lot of water and that is why the glomerulus’ hydrostatic pressure is enormous.

Since at this level we find no proteins, we always speak of relative pressures; one will be compensated by the other, and both make one.

Glomerular hydrostatic pressure is high, and this will allow the water passage. And will not allow proteins to go through. This relationship between the hydrostatic and oncotic pressure is the one which will allow filtration to take place.

 Juntaglomerular Apparatus
 
Next to the glomerulus exists an apparatus denominated “Juxtaglomerular”. It will have several components, being the granular cells the most important.  They are called that way because they contain some granules and these contain a protein called Renine. It is a protease, or a protein which breaks other proteins. This rupture process takes place with water, it is a hydrolysis.

Other element of the juxtaglomerular apparatus is what we call dense Macula, a perception system, a censor. This will test all characteristics which blood might carry. Blood comes through the afferent arteriole. It will trigger a signal at the dense macula’s level. If it comes very charged with ions, then some substances will say “let us secrete”. And if the opposite occurs, they will just send the opposite message.

When we analyze blood we have to take into account two concepts: volemia (blood volume) which will mainly be given by the amount of water blood possesses. And osmolarity which is amount of particles that blood carries, mainly ions like sodium, a very influential substance.

A hyper tense person will have hyper osmolarity, or much sodium in blood. Instead, a person with little sodium (little osmolarity) will have high volemia since both are strictly related to one another.  We have stated that the body always deals with proportions, volume as water, and osmolarity as particles, as ions.

A hyper volemia will come along with a hyper osmolarity. When volemia rises, blood’s water portion will be higher than its particles.

 Complementary Concepts

Blood comes through the afferent arteriole which is a branch of the renal artery. A certain plasmatic flow will also arrive, a certain renal plasmatic flow with its own different characteristics.  In the case of a hyper tense person, the juxtaglomerular apparatus which is analyzing the incoming blood (dense macula is the censor), censes a high osmolarity level and it will send a signal in order to expel these incoming ions. It will emphasize filtering and secretion, thus diminishing re-absorption.

These are the regulating points.

Given their characteristics, sodium and water come along with other substances. Even though this concept sounds contradictory, taking diuretics and raising urine’s amounts a person also raises the eliminated sodium.  

 Renine-Angiotensine-Aldosterone System: the Hydro Saline Equilibrium

A person with a low osmolarity level, hypo tense (a teenager that might faint in hot summer day, for example), suffers a rise of volemia (volume as compared to osmolarity) and the recommendation is to add salt in his food. That is the manner to raise osmolarity. Blood which carries   these characteristics arrives, the dense macula censes it. It perceives a hyper volemia, and a signal triggers: “re-absorb a small quantity”, and inside the tubule it will say “let it out, let it out, do not re-absorb it”. At this dense macula stage, volemia and osmolarity levels can be modified. This yuxta-glomerular apparatus has two parts: a censor which perceives volemia and osmolarity qualities carried by blood, and a system composed by granulated cells which makes and executes -through all this protease and renina- a system of signals which will modify what goes on at the nefron’s level, how that urine will be handled in order to compensate blood characteristics. This is denominated renine-angiotensine-aldosterone system. And when we refer to the body’s hydro saline equilibrium, to a great extent, we are referring to this system.  

This is how osmolarity and volemia are regulated in blood. Granullar cells are to be found in the juxtaglomerular apparatus, next to the glomerulus, and belong to the nefron which is inside the Malpighi Pyramid also inside the kidney.

Once the dense macula sends a signal, renine will enter blood. Blood has a protein called angiotensinogen, synthesized in the liver. Renine, which is a protease, will break that angiotensinogen and turn it into angiotensine I, angiotensinogen’s active state. As a matter of fact we should state that it possesses a greater activity since angiotensine I is an intermediary activity state.  It is angiotensine II, however, the one which will show a maximum activity. Renine (which transformed angiotensinogen into angiotensine) keeps on circulating inside the blood, and this blood eventually reaches the heart. Mainly in the heart (though eventually we might also find it in other tissues) there is an enzyme called angiotensine converter enzyme (ace). An enzyme is a protein which will help to provoke certain reactions. This is how angiotensine I becomes angiotensine II, and the last one really, happens to be the one which shows a very active state.  It is a vessel constrictor and it will obviously obstruct the blood passage thus also raising blood’s pressure. If I raise my blood’s osmolarity, I raise the amount of particles and the pressure too.  Some way of raising the blood’s pressure is allowing sodium to get in (I raise osmolarity). Another manner is through vessel constriction, given by angiotensine II.  Volemia will diminish. However, this is not the only course of action; we will see that it possesses a much more direct action.   ACE will have a double action. On the one hand it will turn angiotensine I into angiotensine II, thus having a vessel constrictor power, on the other ECA deactivates brad-quinine, a vessel dilator.  Therefore we see that ECA possesses a double vessel constrictor power (it activates a vessel constrictor and deactivates a vessel dilator). Most of hyper tension medicines are ECA inhibitors.    Angiotensine II besides its own action (being a Vessel constrictor) will also enter the suprarenal gland, which is a triangular shaped nervous structure which secretes lots of different neuronal hormones. Angiotensine, however, will stimulate only the release of one of them:  aldosterone. Aldosterone will act in the kidney’s tubule, where re-absorption and secretion is produced.   Aldosterone will stimulate sodium re-absorption and potassium and hydrogen secretion.

Angiotensine does not only raise arterial pressure, it does it getting right to the point: stimulates aldosterone liberation, this reaches the renal tubule, stimulates sodium re-absorption, raising directly that osmolarity, it diminishes volemia and it will also raise potassium and hydrogen secretion.

The problem with this is that if a certain amount of aldosterone is released, a person might suffer from hyper potasemia, and a decomposition of the base acid will take place since these protons or hydrogen regulates our body’s major acidity level. 
The renine angiotensine aldosterone system is then a vessel constriction one, triggered by the dense macula and performed by the granulated cell.

Besides, this system also stimulates another mechanism in the heart through the NFA (Natri-ureic factor –sodium-, Atrial –since we find it in the heart’s auricles). It stimulates sodium secretion. 
In spite of the fact that it comes from the heart we can also find it in other tissues as well.
Sodium excretion will produce hypo tension. Angiotensine II will centrally stimulate an SNC structure (called hypothalamus) where the anti-diuretic hormone (ADH) will be produced.
It stimulates the sodium re-absorption. NFA will act as hypo tensor, aldosterone and ADH as hyper tensors. Renine, angiotensine are hyper tensors.
The sympathetic system will produce vessel constriction.
Example: during any acute dehydration, volemia will be diminished, thus the baro receptors (we find them in auricles, inside the carotid and aortic key) will be diminished and the osmo receptors (within the hypothalamus) magnified. 

As a whole, these actions will provoke thirst, a neuronal signal which stimulates water search and ADH secretion (just as the angiotensine II). This raises re-absorption of sodium inside the collector tubule, diminishing water excretion. Thirst will stimulate search for water, and water will be drank.   This way the body raises the volume and diminishes plasmatic osmolarity taking it to normal levels. This is the normal process.

 Sodium Excretion Regulation Mechanisms

There are three mechanisms for sodium excretion. We shall remember that its entrance is not regulated, only its way out.  
 
The main modifiers are: glomerular filtration volume, aldosterone and a third factor which does not depend upon the former ones.  Changes in plasmatic volume will act as a trigger of these regulating mechanisms.

1. VFG which depends upon the RPA (renal plasmatic flow), the main regulator, and the FNP (filtration net pressure). The amount of blood which reaches the glomerulus will be the main regulator of how much is filtered.  If I ingest more sodium, which is what usually happens with hyper tense people, plasma and osmo receptors’ osmolarity will also rise. This triggers thirst and water drinking.  ADH is also produced and water excretion diminishes. These mechanisms as a whole produce the raise of the plasmatic volume. Plasma’s oncotic pressure thus lowers and so does in blood. Then when blood reaches the capillary, pressure will be lower. Oncotic pressure in the glomerular capillary lowers.  NFP then raises, VFG too and the same happens with sodium excretion.
Plasmatic volume, on the other hand, stimulates baro receptors (volume receptors) consequently diminishing the renal sympathetic tone since the sympathetic provokes vessel constriction.  This is what we know as retro alimentation system.  Pathology appears when it stops functioning.  Renal sympathetic tone will diminish as the afferent arteriole dilates thus allowing the rise of the renal plasmatic flow, also rising the filtration net pressure and also the VFG and sodium excretion.  Due to all these reasons, VFG main regulator will then be the FPR.

2. Aldsoterone will be stimulated by: High potassium levels (we should remember that aldosterone stimulates potassium excretion).
Angiotensine:
ACTH Neuronal signal which will independently stimulate aldoesrone secretion.
FNA: this factor will stimulate sodium secretion. Therefore: FNA diminution will stimulate aldosterone secretion. That was sodium secretion will not vanish. 
Sodium Pressure Diminution in Blood.
Renine triggers are: rise of the renal sympathetic (vessel constrictor)
Volemia’s change. Tubular liquid composition change.
Hydroestatic glomerular pressure rise.
Baro receptor diminution.
 
Then, a rise in the sodium levels (i.e. a hyper tense person) raises plasma osmopolarity and stimulates the osmo receptors. On one hand this stimulates thirst mechanisms and provokes water ingestion.

On the other stimulates DHA which in turn diminishes water excretion since stimulates re-absorption.
Due to these two reasons plasma’s volume rises and baro receptors are stimulated, and renal sympathetic tone diminishes due to the retro alimentation system. This diminution produces the afferent arteriole dilation due to its vessel constriction action diminution and renal perfusion raises thus provoking a large blood income. Renine secretion diminishes slowing the renine-angiotensine-aldosterone system, and sodium excretion is stimulated.

3. As sodium ingestion raises, appears what we know as “third factor effect” which will produce sodium excretion rise.

These are five mechanisms.
Renal sympathetic diminishes.

Angiotensine II also diminishes, and so does aldosterone, consequently raising sodium excretion.
FNA rises and sodium excretion is produced (natri-uresis)
Capillary hydrostatic pressure rises and oncotic pressure in capillary diminishes.
Glomerular hydrostatic pressure diminishes.
 
Therefore a large rise of sodium ingestion will produce the growth of plasma’s osmopolarity and the subsequent stimulation of the osmo receptors. This stimulates thirst and water ingestion.
On the other hand stimulates DHA which in turn diminishes water excretion since the last stimulates re-absorption.
 
Plasma volume rises due to these two reasons.

Therefore plasma’s oncotic pressure diminishes. Per tubular capillary oncotic pressure diminishes and then sodium re-absorption in the proximal tubular lowers and sodium excretion rises. On the other hand FNA also stimulates sodium excretion.

On the other hand, plasmatic volume rise stimulates the baro receptors, thus diminishing the renal sympathetic tone (due to the retro alimentation system. This lowering of the renal sympathetic tone produces dilation of the afferent arteriole due to the diminution of its vessel constriction action and raises the renal perfusion. Re-absorption of the capillary tubular also rises. Therefore, sodium diminishes re-absorption in the proximal tubular and excretion raises.

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