FILTRATION - also known as "ULTRAFILTRATION."

The kidneys filter plasma.  Let's have a look at the structures where filtration takes place in the kidneys!  The central filtration device is the "glomerulus."  While the glomerulus is the central part of the filtration apparatus, it is really not the only part.  Let's start by looking at a couple of diagrams!

Diagram B

Diagram C

Look in diagrams, A and B, and find the "glomerulus."  The glomerulus is really a twisted bundle of high pressure capillaries.  Notice that the glomerulus receives blood from a high pressure "afferent arteriole."  Because the glomerular capillary membrane is 100-400 times more permeable to ions than other capillaries in the body, plasma is readily filtered through the walls of the glomerular capillaries, resulting into the movement of fluid into a surrounding capsule known as the glomerular capsule (or Bowman's capsule).  In diagram A, the space inside Bowman's capsule is labeled, "capsular space," although it is also called the capsular lumen.  Bowman's capsule forms a tight seal around the glomerulus such that all of the fluid being filtered out of the glomerulus is caught in the capsular space.  The plasma that is filtered is known as "renal filtrate" and is similar to plasma, except that the circulating globular proteins are too big to be filtered through the "holes" in the glomerulus!  So the "renal" filtrate is plasma without the globular proteins!  Cells are way too big to be filtered, so we recognize that the kidney filters plasma, not blood.

But why are the glomerular capillaries 100-400 times more permeable to ions than are other capillaries in the body?  Look back at diagram A; note the complex structures involved!  First, the capillary endothelium has large pores as well as gaps between cells.  The pores and gaps are only small enough to stop red and white blood cells; this porous capillary endothelium is known as the "fenestrated endothelium" of the glomeruli.  The word fenestration means window and refers to the large pores in the endothelium of the glomerular capillaries!  The capillary basement membrane also has pores which allow passage of substances with molecular weights as great as 70,000.   Thus, the basement membrane excludes passage of the large globular proteins.

Now, let's look at Diagram A again!  Notice in the lower panel (the magnification) that there are modified epithelial cells in Bowman's capsule called podocytes.  Podocytes have have inter-digitating (inter-locking) finger-like projections, called pedicels.  Notice that the pedicels form a fine meshwork around the glomerular capillaries.  The gaps between the pedicels are known as "filtration slits."  Substances which are filtred through the basement membrane of the capillaries can fit through the filtration slits formed by the pedicels of the podocytes.  Note, however, that despite the presence of these large filtration slits, substances with increasingly large molecular weights have an increasingly difficult time to pass through both the pores and slits.  The larger the molecule, the less likely it is to pass through the filtration device, until we reach molecules with a molecular weight of approximately 70,000, at which point a molecule might just  barely fit through if it had an elongated shape and was able to squeeze through "sideways," but otherwise is unlikely to be filtered.

So why bother with podocytes, pedicels and filtration slits.  In addition to assisting with filtration, the podocytes wrap entirely around the glomerular capillaries, allowing the glomerular capillary network to withstand pressures about twice as high as encountered by any other capillaries in the body.

The glomerulus is a high pressure capillary network and is the renal structure responsible for filtration of plasma.  The glomerulus is very well suited for filtration.  A high afferent (incoming) arteriolar pressure provides a high hydrostatic pressure relative to other body arterioles.  Blood from the afferent arterioles is passed through the glomerulus for filtration.  Blood leaving the glomerulus enters the efferent arterioles.  The efferent arterioles generate a lot of resistance, such that pressure remains high within both the glomerular capillaries and afferent arterioles.  The efferent arterioles branch into the peritubular capillaries where re-absorption predominates under the influence of colloid osmotic pressure generated by proteins (discussed below!).

It isn't pretty, is it?  The table below provides the pressures at the numbered sites in the diagram above!  Below the table, you will find an explanation of the forces driving filtration and re-absorption and why these sites are important.

Filtration is controlled to some extent by the diameter of the afferent and efferent arterioles; there is very little resistance across the capillary bed in the glomerulus, such that very little hydrostatic pressure is lost between the afferent (60 mmHg) and efferent (55 mmHg) arterioles.  The "vascular bed" in the "immediate glomerular region" has 3 important sites (labeled 1, 2, and 3 in the diagram above):

Site 1 - afferent arteriolar entry into the glomerulus
Site 2 - efferent arteriolar exit from the glomerulus
Site 3 - peritubular capillary region; moving away from the glomerulus; the point where the peritubular capillaries branch away from the efferent arteriole and begin to surround the convoluted portions of the nephron

Values are shown as positive or negative.  Positive values indicate that hydrostatic pressure supports filtration while negative values indicate that a force is opposing filtration of plasma out of the vascular compartment (ie. colloid osmotic pressure supports re-absorption back into the vascular compartment, Bowman's capsule pressure is the fluid pressure within the capsule lumen, and plasma must be filtered out of the glomeruli with sufficient pressure to overcome resistance from the fluid pressure already existing within Boman's capsule).  In other words, forces moving fluid out of the blood (filtration) are indicated as positive values, while forces promoting reabsorption back into the blood, or opposing filtration are indicated by negative values.

Fluid is forced out of capillaries (filtration) by blood pressure (hydrostatic pressure).  As plasma is filtered, globular proteins are concentrated in the blood passing through the glomerulus, as globular proteins are too large to be filtered.  Therefore, fluid leaving the glomerulus in the efferent arteriole has a higher colloid osmotic pressure than fluid entering the glomerulus in the afferent arteriole.  Fluid is drawn back into capillaries (re-absorption) by the increase in colloid osmotic pressure following concentration of protein in plasma passing into the efferent arteriole.  The hydrostatic pressure that exists within Bowman's capsule and the wall of Bowman's capsule, itself, represent a physical force opposing filtration into the renal tubule... this is labeled "Bowman's capsule pressure" in the table.  Thus, Site 1 (blood entering the glomerulus) is ideal for rapid filtration (+17 mmHg); filtration has almost ceased at Site 2 (+2 mmHg) and conditions are optimal for re-absorption at site 3 (peritubular capillaries) as we begin to move away from the glomerulus (-22 mmHg).

Note that about 180 liters of filtrate are produced each day, with 1-2 liters ultimately being urinated and the remainder, almost the entire 180 liters filtered, being reabsorbed.  Thus, under normal circumstances we are producing only about 1 ml of urine/min.  Urine may be considered as filtrate which actually appears in the bladder - remember, fluid in the bladder is not available for re-absorption in humans, and fluid in the bladder is considered lost.  Recall that the major route of fluid loss at rest is urine production, about 1.5 liters per day.

Note also that plasma filtration at the kidneys depends on a renal arterial pressure of 70-100 mmHg and an afferent arteriolar pressure of 60 mmHg. Thus, filtration and eventually urination are dependent on blood pressure.  If mean systemic arterial pressure drops below 45-55 mmHg (eg. dehydration, hypovolemia), ultra-filtration and urine formation are severely compromised and may cease.

RE-ABSORPTION involves several structures in and around the nephrons.

Approximately 178.5 L of the 180 L of filtrate produced every day is reabsorbed (99.2% of filtrate is reabsorbed).  Urine output is about 1.5 L per day but can fall to conserve water (400 mL/day) or increase dramatically to rid the body of excess water.  When urine output falls into the 400-600 mL/day range, it is nearly impossible to maintain a normal electrolyte and pH balance, and survival is in question!

Proximal Convoluted Tubule (PCT) Cells have large numbers of mitochondria and a large, very convoluted lumenal surface for good absorption.  This convoluted cell surface is characterized by the presence of extensive microvilli (brush border).  The cell surfaces have Na⁺ channels which allow Na⁺ to diffuse passively into the cells lining the tubule.  The Na⁺ is then actively pumped, by the Na⁺/K⁺ pump, into the ISF around the tubule, from which it can be passively reabsorbed back into plasma. 

Both Cl^- and H₂O passively follow the Na⁺ into the ISF in the region of the PCT; recall that the H₂O follows Na⁺ in the form of a sphere of hydration while Cl^- follows Na⁺ because of the charge attraction!  Approximately 65% of salt and water re-absorption occurs in the proximal tubule.  As the proximal tubule is freely permeable to salt and water, all of this reabsorption does not significantly alter the concentration of the filtrate.  Recall that the renal filtrate is initially isosmotic with plasma.  This means that the proximal tubule ends up reabsorbing an isosmotic solution from an isosmotic solution.  At this point, then, it might seem crazy to have a PCT... but it is important to note that the very important tubular maxima mechanisms described below are active only in this energetic region of the nephron, and are tied to Na⁺ reabsorption.  This energetic region of the nephron is loaded with mitochondria and can manufacture its own glucose when necessary (gluconeogenesis)!

Nephron Loop (Loop of Henle): The cells of the nephron loop are less energetic than those of the proximal tubule but they have a high permeability (notably in the descending limb) to numerous substances.  Filtrate continues to be absorbed in the loop of Henle but, here, the concentration of the renal filtrate is significantly altered. An additional 20% of the renal filtrate will be reabsorbed here; meaning that filtrate volume has been reduced by a total of 85% by the time we ascend back into the cortex and enter the distal convoluted tubule.  Although filtrate enters the descending limb and then the ascending limb, we will consider the processes that occur in the two limbs in reverse order to facilitate explanation of how the kidneys concentrate urine.

Ascending Limb of the nephron loop: The ascending limb is impermeable to water.  But it is very permeable to ions as it has secondary active co-transport proteins which strongly reabsorb Na⁺, Cl^- and K⁺ out of the lumen of the nephron and into the medullary interstitium.  These secondary active co-transporters use the energy provided by the Na+ concentration gradient to reabsorb all 3 ions.  How fascinating is that... a secondary active co-transporter that moves 3 ions at the same time!!!  This means that Na⁺, Cl^- and K⁺ accumulate in the ISF in the medullary region surrounding the nephron loop.  Since the thick-walled ascending limb is impermeable to water, the concentration of the filtrate decreases as solutes are actively pumped out on the way up the ascending tubule. Simply put, the ascending limb helps concentrate solutes in the medulla!  In order to produce a concentrated urine, the medulla must be a "concentrated place!" (ie. it must have a high solute concentration)

Descending Limb of the nephron loop: As filtrate moves down through the descending limb, it is exposed to the high solute concentrations pumped into the medullary ISF by the ascending limb.  The descending limb is permeable to water and so water moves out of the descending tubule and into the highly concentrated medullary ISF.  As water leaves the filtrate moving down through the descending limb, the filtrate becomes increasingly concentrated. Simply put, the descending limb concentrates solutes in the nephron so it will be easier for the ascending limb to pump those solutes into the ISF of the medulla!

  The more salt actively pumped out of the ascending limb of the nephron loop, the more concentrated will become the fluid passing through the descending limb into the ascending limb. ie. by pumping out solutes, the ascending limb indirectly concentrates fluid being delivered to the ascending limb by the descending limb.  This "symbiotic functional relationship" between the ascending and descending limb is known as the countercurrent multiplier system!

Vasa Recta: These long capillary loops parallel the nephron loops. The plasma concentration in the vasa recta parallels that in the nephron loops because the vasa recta are freely permeable to salt and water.  Plasma and ISF are always trying to come to equilibrium such that plasma concentrations in the vasa recta continuously parallel the concentration of the filtrate in the neighboring region of the renal tubule.  Solutes tend to diffuse from the ISF into the vasa recta as the vasa recta descends into the medulla and solutes tend to diffuse out of the vasa recta and into the ISF as the vasa recta ascend out of the medulla.  Solutes diffusing out of the ascending limb on the way up promptly diffuse back into the descending limb and are carried back down.  Blood flow through the vasa recta is extremely slow to allow time for equilibration of the steep concentration gradients.  Simply put, the vasa recta mimic the prevailing concentration gradient in the kidney tubules; this helps trap solutes in the medullary region, helping to maintain the high solute concentration in the ISF of the medulla.

Why is the kidney so overtly concerned about maintaining a high solute concentration in the medulla?  Recall that this high solute concentration in the medulla is absolutely necessary in order to produce a concentrated urine (read on!!!).

  By the time we reach the distal tubule, we have already reabsorbed back 85% of our filtrate volume.  Now, this region of the nephron is permeable to water, although the degree of water permeability in this region is subject to regulation by ADH.  ADH causes incorporation of more water channels into the membrane of the distal tubule and collecting duct so that more water can be reabsorbed, in turn reducing urine output.

Recall that ADH is synthesized in the hypothalamus but is stored and released from the posterior pituitary.  Again, this regulated water re-absorption is reduced in untreated diabetes insipidus, due to an insufficiency of ADH, leading to PUPD.  When the filtrate reaches the distal convoluted tubule and collecting duct, H₂O begins to follow the Na⁺ pumped out in the ascending limb of the nephron loop.  As the collecting duct drops back through the medullary region on its way to the renal pelvis, the collecting duct must pass right through the very concentrated medullary region.  If ADH has caused an increase in the number of functional water channels in the collecting duct, the filtrate will become increasingly concentrated as it passes through the medulla and water is rapidly reabsorbed from the kidney tubule back into the bloodstream.

Thus, for the kidney to produce very concentrated urine it must produce a very concentrated filtrate in the descending limb of the loop of Henle, so that lots and lots of Na⁺ and Cl^- can be pumped out of the ascending limb and then lots and lots of H₂O can be reabsorbed from the distal tubule and collecting duct.  Recall that urea recycling between the collecting ducts and the nephron loop also helps maintain the high solute concentration in the medulla!  The longer the loops and the greater the number of loops, the more time, distance and surface area available to create gradients and the greater the ability to produce concentrated urine.  Thus, the nephron loops, the vasa recta and the distal tubule and collecting duct work in harmony to produce a concentrated urine.  The concentration of urine remains unchanged once it reaches the bladder.

Total length of a nephron:

  The average nephron is 4 cm in length from the beginning of filtration to entry into the pelvic region of the kidney.  This "long" distance allows adequate time for the kidney to "regulate" the contents of fluid entering the tubule.