Enrico Tiepolo
Kidneys and body fluids
The kidneys are organs in charge of
maintaining the right values of volume and
composition of the plasma and as a
consequence of eliminating metabolites
and exogenous substances, holding
back solutes that are necessary for the
organism. The latter control function is
carried out by the elimination of water and
solutes through urine; the fundamental
mechanism is a filter of two stages:
1. Ultrafiltration of plasma (only
macromolecules and cells are held),
2. Reabsorption and/or secretion of
solutes and water through a very
selective and regulated mechanism.
The kidney is constituted by a high number of individual units (nephrons) each formed by a
glomerulus and a tubule.
The kidney displays a cortex, essentially constituted by glomeruli (where the ultrafiltration happens),
and a medullary region (pyramids), mostly constituted by tubules (Henle’s loops) (where
reabsorption/ secretion happens).
Distinct regions of the kidneys
- Cortical zone, in which arterial blood forms small glomeruli where the same blood gets
filtered. These glomeruli can be positioned in the more external part (cortical
glomeruli) and in the proximal limit to the medulla (juxtamedullary glomeruli). The
liquid obtained by the mechanism of filtration is then gathered in Bowman’s capsule,
that wraps capillaries of the glomeruli and creates tubules. Between glomeruli,
convolutions of tubules can be observed: before they start their path towards the medullary
zone, proximal convoluted tubules, and on their return path from the medullary
zone, distal convoluted tubules.
- Medullary zone, which is constituted by pyramids where conducts
run parallel:
o Tubules, descending at variable heights, creating
Henle’s loops and going back to the cortical zone.
o Excretory ducts, gathering contents of distal
convoluted tubules and, after they cross the medullary
zone, convey in the calyxes of the renal pelvis.
o Vessels that go down parallel to the tubules in the
medullary zone and then go back up at the
corticomedullary junction are called vasa recta.
Vascularization of the kidneys is very important for its function.
Arterial blood enters the kidneys by the renal arteries, which are 2 branches of the descending
aorta. From here they divide into segmental arteries that reach the various portions of the kidney.
Each segmental artery will further divide into interlobar arteries, which
surround the renal pyramids and run up to the corticomedullary junction,
where they become arcuate arteries.
From the arcuate arteries, radial cortical arteries depart, giving rise to
one arteriole for each glomerulus. The afferent arteriole enters the
glomerulus, and the efferent arteriole exits it, reaching a peritubular
capillary bed from where blood flows into radial cortical venules, that
go back to arcuate veins and then to interlobar veins.
112 Body At Work II
, Enrico Tiepolo
With respect to normal arterioles, efferent arterioles present lower hydrostatic pressure and higher
oncotic pressure (since during the filtration in the glomerulus they lost water and solutes, leaving a higher
concentration of proteins in the blood), making it so that these factors favor a huge water and solutes
reabsorption.
In the medullary zone, vascularization is constituted by vessels that radially descend along the pyramids
and then go back up, called vasa recta. These vasa recta originate from the radial cortical arteries like
the afferent arterioles, but instead of going to the glomerulus, they reach down in the medulla. Since
they don’t pass through a glomerulus, they present higher hydrostatic pressure and the same oncotic
pressure as normal arteries.
Efferent arterioles of juxtamedullary glomeruli, instead of creating peritubular capillary beds (like it
happens in the cortex), run down to the medullary zone and create vasa recta spuria. The blood from
vasa recta spuria will then travel back to either the arcuate artery or the arcuate vein.
Thanks to this anatomical organization, the tubular transports create, in the medullary interstice, an
osmotic gradient that reaches its maximum at the papilla (1200 mOsmol/Kg), reaching 5 times more
than the osmolarity of plasma (which is around 275 mOsmol/Kg), while the tubular lumen becomes
hypo-osmotic with respect to the medullary interstitium.
Every glomerulus, with its own collecting tubule and its capillary bed, makes a functional unit that is
relatively independent, the nephron.
There are 1.2 million nephrons in each kidney, and they work in parallel, contributing to the
production of urine.
Nephrons do not work all the same as the composition of urine of cortical nephrons with respect to the
juxtamedullary ones is different.
The steps of urine production are the following:
a) The blood arrives through the afferent arteriole and gets filtrated through the glomerulus.
About 1/5 of the blood that enters the kidney is typically filtered. “Filter” means to let something
through, together with the fluid, and retain something else (formed elements of blood). In the
glomerulus, molecules smaller that about 7 nm size are generally able to go through. This implies
that proteins, larger than that, will be gradually concentrated along the glomerular capillaries,
and the plasma leaving the glomerulus, in the efferent arteriole, will have an oncotic pressure
some 25% higher than the plasma in the afferent arteriole (cause blood will be more
concentrated). No exchange of gases or solutes has occurred in the glomerulus, but only the
filtration of part of the content, so the content of the blood in the efferent arteriole will be typical
arterial content.
b) The filtrated liquid passes through the proximal convoluted tubules and runs till Henle’s loop.
c) Then the liquid reaches the distal convoluted tubule portion and gets gathered into the collecting
ducts towards the papilla.
o This phase is selective and highly regulated: tubular transport is active in most cases.
The blood that leaves the glomerulus through the efferent arteriole, will generate a peritubular capillary
bed that perfuses the proximal and distal convoluted tubules (in the cortex), and also Henle’s loop when
this does not penetrate deep in the medulla. These vessels, perfusing Henle’s loops, are the vasa recta
spuria; they have the same function as the vasa recta, that depart directly from the arcuate arteries and
perfuse the medullary pyramid, except they contain plasma with a higher oncotic pressure (due to the
previous filtration at the glomerulus), which will therefore have a higher tendency to extract water and
solutes.
Again, the nephron works as a two-stages filter that:
- Completely detains cells of the blood and macromolecules (>70kDa) in the blood and delays the
passage of medium-size molecules (10-70 kDa) at the level of the glomerulus.
- Systems that translocate ions and make cotransport/ antiport allow the reabsorption of 97% of
filtered solutes.
- Passive reabsorption of water is regulated, so that osmolarity of urine can vary around the normal
value of 1.000 mosm/L.
113 Body At Work II
, Enrico Tiepolo
The kidney does not know which substances are good, neutral or toxic, and would need an innumerable
set of specific transport systems to handle the disposition of toxic substances preserving the good ones. It
therefore works according to a completely different rationale: filter everything, reabsorb what is
needed (such as glucose, amino acids, bicarbonate...). This is called non-selective filtration.
Filtering will therefore be based merely on size and partly on electric charge, while a limited number of
active, selective transport mechanisms reabsorb what is needed.
Non-selective filtration demonstrates to be the best mechanism as, followed by reabsorption of water
and electrolytes, leaves in the tubule all hydrophilic molecules that are not actively reabsorbed.
Therefore, in order to extrude a lipophilic molecule, we will make it more hydrophilic and, once it's
been filtered in the tubular system, we won’t reabsorb it.
Active transport needs to be present to reabsorb instead important substances like glucose and amino
acids.
Kidneys therefore regulate:
1. Volume of body fluids: as water is passively reabsorbed, then the quantity of solutes that gets
eliminated determines the quantity of liquids that gets eliminated too.
2. Plasma osmolarity and body fluids osmolarity are also regulated by the passive mechanism
of re-entry of water that compensates the alterations of plasma osmolarity.
3. Plasma concentrations of ions and small molecules through transport systems regulation.
4. Hydrogen ions and bicarbonate concentrations and therefore of pH of extracellular liquids.
Sodium’s role and water balance
The leading role in all the renal systems of transport is the one of Na+.
Sodium tends to passively diffuse into the epithelial cells’ cytoplasm as its concentration is higher outside
the cell and, as the internal membrane potential is negative, the positive charge of Na+ wants to move
towards the more negative cytoplasm.
The fact that its intracellular concentration is low, and the intracellular membrane potential is negative
are both due to the Na/K-ATPase pump that is expressed on the basolateral domain of the
epithelium (that pumps out Na+ in exchange for K+). The passage of sodium along the apical
membrane is a dissipative movement of charges and its free energy is utilized coupling the Na flux with
cotransports or antiports of other ionic species or small biological molecules (e.g. glucose and amino
acids) that need to be transported against gradient.
As sodium is the main extracellular solute, the net
passage of it from the lumen of the tubule towards the interstice
creates an osmotic unbalance as the tubular lumen becomes
hypo-osmotic with respect to the medullary interstitium.
Sodium enters the epithelium lining the tubule following its
concentration of gradient and is then pumped in the
interstitium by a Na+/K+ ATPase.
Part of the free energy liberated after the flow of sodium from
the lumen to the interstitium is used for the creation of a
difference in osmotic pressure, which guides the passive
reabsorption of water from the tubular lumen towards the
interstice to balance the difference in osmolarity; water flow can
follow both a paracellular way and a transcellular way, as
some tiny little spaces exist between cells of the lining epithelium
but also the membrane of these cells is permeable to water.
In the distal portions of the tubules paracellular permeability is
very low and therefore epithelium is impermeable to water. In
particular the ascending portion of Henle’s loop and the DCT are completely impermeable to water,
while the connecting and collecting tubules allow water passage highly regulated through specific protein
pores called aquaporins.
114 Body At Work II
Kidneys and body fluids
The kidneys are organs in charge of
maintaining the right values of volume and
composition of the plasma and as a
consequence of eliminating metabolites
and exogenous substances, holding
back solutes that are necessary for the
organism. The latter control function is
carried out by the elimination of water and
solutes through urine; the fundamental
mechanism is a filter of two stages:
1. Ultrafiltration of plasma (only
macromolecules and cells are held),
2. Reabsorption and/or secretion of
solutes and water through a very
selective and regulated mechanism.
The kidney is constituted by a high number of individual units (nephrons) each formed by a
glomerulus and a tubule.
The kidney displays a cortex, essentially constituted by glomeruli (where the ultrafiltration happens),
and a medullary region (pyramids), mostly constituted by tubules (Henle’s loops) (where
reabsorption/ secretion happens).
Distinct regions of the kidneys
- Cortical zone, in which arterial blood forms small glomeruli where the same blood gets
filtered. These glomeruli can be positioned in the more external part (cortical
glomeruli) and in the proximal limit to the medulla (juxtamedullary glomeruli). The
liquid obtained by the mechanism of filtration is then gathered in Bowman’s capsule,
that wraps capillaries of the glomeruli and creates tubules. Between glomeruli,
convolutions of tubules can be observed: before they start their path towards the medullary
zone, proximal convoluted tubules, and on their return path from the medullary
zone, distal convoluted tubules.
- Medullary zone, which is constituted by pyramids where conducts
run parallel:
o Tubules, descending at variable heights, creating
Henle’s loops and going back to the cortical zone.
o Excretory ducts, gathering contents of distal
convoluted tubules and, after they cross the medullary
zone, convey in the calyxes of the renal pelvis.
o Vessels that go down parallel to the tubules in the
medullary zone and then go back up at the
corticomedullary junction are called vasa recta.
Vascularization of the kidneys is very important for its function.
Arterial blood enters the kidneys by the renal arteries, which are 2 branches of the descending
aorta. From here they divide into segmental arteries that reach the various portions of the kidney.
Each segmental artery will further divide into interlobar arteries, which
surround the renal pyramids and run up to the corticomedullary junction,
where they become arcuate arteries.
From the arcuate arteries, radial cortical arteries depart, giving rise to
one arteriole for each glomerulus. The afferent arteriole enters the
glomerulus, and the efferent arteriole exits it, reaching a peritubular
capillary bed from where blood flows into radial cortical venules, that
go back to arcuate veins and then to interlobar veins.
112 Body At Work II
, Enrico Tiepolo
With respect to normal arterioles, efferent arterioles present lower hydrostatic pressure and higher
oncotic pressure (since during the filtration in the glomerulus they lost water and solutes, leaving a higher
concentration of proteins in the blood), making it so that these factors favor a huge water and solutes
reabsorption.
In the medullary zone, vascularization is constituted by vessels that radially descend along the pyramids
and then go back up, called vasa recta. These vasa recta originate from the radial cortical arteries like
the afferent arterioles, but instead of going to the glomerulus, they reach down in the medulla. Since
they don’t pass through a glomerulus, they present higher hydrostatic pressure and the same oncotic
pressure as normal arteries.
Efferent arterioles of juxtamedullary glomeruli, instead of creating peritubular capillary beds (like it
happens in the cortex), run down to the medullary zone and create vasa recta spuria. The blood from
vasa recta spuria will then travel back to either the arcuate artery or the arcuate vein.
Thanks to this anatomical organization, the tubular transports create, in the medullary interstice, an
osmotic gradient that reaches its maximum at the papilla (1200 mOsmol/Kg), reaching 5 times more
than the osmolarity of plasma (which is around 275 mOsmol/Kg), while the tubular lumen becomes
hypo-osmotic with respect to the medullary interstitium.
Every glomerulus, with its own collecting tubule and its capillary bed, makes a functional unit that is
relatively independent, the nephron.
There are 1.2 million nephrons in each kidney, and they work in parallel, contributing to the
production of urine.
Nephrons do not work all the same as the composition of urine of cortical nephrons with respect to the
juxtamedullary ones is different.
The steps of urine production are the following:
a) The blood arrives through the afferent arteriole and gets filtrated through the glomerulus.
About 1/5 of the blood that enters the kidney is typically filtered. “Filter” means to let something
through, together with the fluid, and retain something else (formed elements of blood). In the
glomerulus, molecules smaller that about 7 nm size are generally able to go through. This implies
that proteins, larger than that, will be gradually concentrated along the glomerular capillaries,
and the plasma leaving the glomerulus, in the efferent arteriole, will have an oncotic pressure
some 25% higher than the plasma in the afferent arteriole (cause blood will be more
concentrated). No exchange of gases or solutes has occurred in the glomerulus, but only the
filtration of part of the content, so the content of the blood in the efferent arteriole will be typical
arterial content.
b) The filtrated liquid passes through the proximal convoluted tubules and runs till Henle’s loop.
c) Then the liquid reaches the distal convoluted tubule portion and gets gathered into the collecting
ducts towards the papilla.
o This phase is selective and highly regulated: tubular transport is active in most cases.
The blood that leaves the glomerulus through the efferent arteriole, will generate a peritubular capillary
bed that perfuses the proximal and distal convoluted tubules (in the cortex), and also Henle’s loop when
this does not penetrate deep in the medulla. These vessels, perfusing Henle’s loops, are the vasa recta
spuria; they have the same function as the vasa recta, that depart directly from the arcuate arteries and
perfuse the medullary pyramid, except they contain plasma with a higher oncotic pressure (due to the
previous filtration at the glomerulus), which will therefore have a higher tendency to extract water and
solutes.
Again, the nephron works as a two-stages filter that:
- Completely detains cells of the blood and macromolecules (>70kDa) in the blood and delays the
passage of medium-size molecules (10-70 kDa) at the level of the glomerulus.
- Systems that translocate ions and make cotransport/ antiport allow the reabsorption of 97% of
filtered solutes.
- Passive reabsorption of water is regulated, so that osmolarity of urine can vary around the normal
value of 1.000 mosm/L.
113 Body At Work II
, Enrico Tiepolo
The kidney does not know which substances are good, neutral or toxic, and would need an innumerable
set of specific transport systems to handle the disposition of toxic substances preserving the good ones. It
therefore works according to a completely different rationale: filter everything, reabsorb what is
needed (such as glucose, amino acids, bicarbonate...). This is called non-selective filtration.
Filtering will therefore be based merely on size and partly on electric charge, while a limited number of
active, selective transport mechanisms reabsorb what is needed.
Non-selective filtration demonstrates to be the best mechanism as, followed by reabsorption of water
and electrolytes, leaves in the tubule all hydrophilic molecules that are not actively reabsorbed.
Therefore, in order to extrude a lipophilic molecule, we will make it more hydrophilic and, once it's
been filtered in the tubular system, we won’t reabsorb it.
Active transport needs to be present to reabsorb instead important substances like glucose and amino
acids.
Kidneys therefore regulate:
1. Volume of body fluids: as water is passively reabsorbed, then the quantity of solutes that gets
eliminated determines the quantity of liquids that gets eliminated too.
2. Plasma osmolarity and body fluids osmolarity are also regulated by the passive mechanism
of re-entry of water that compensates the alterations of plasma osmolarity.
3. Plasma concentrations of ions and small molecules through transport systems regulation.
4. Hydrogen ions and bicarbonate concentrations and therefore of pH of extracellular liquids.
Sodium’s role and water balance
The leading role in all the renal systems of transport is the one of Na+.
Sodium tends to passively diffuse into the epithelial cells’ cytoplasm as its concentration is higher outside
the cell and, as the internal membrane potential is negative, the positive charge of Na+ wants to move
towards the more negative cytoplasm.
The fact that its intracellular concentration is low, and the intracellular membrane potential is negative
are both due to the Na/K-ATPase pump that is expressed on the basolateral domain of the
epithelium (that pumps out Na+ in exchange for K+). The passage of sodium along the apical
membrane is a dissipative movement of charges and its free energy is utilized coupling the Na flux with
cotransports or antiports of other ionic species or small biological molecules (e.g. glucose and amino
acids) that need to be transported against gradient.
As sodium is the main extracellular solute, the net
passage of it from the lumen of the tubule towards the interstice
creates an osmotic unbalance as the tubular lumen becomes
hypo-osmotic with respect to the medullary interstitium.
Sodium enters the epithelium lining the tubule following its
concentration of gradient and is then pumped in the
interstitium by a Na+/K+ ATPase.
Part of the free energy liberated after the flow of sodium from
the lumen to the interstitium is used for the creation of a
difference in osmotic pressure, which guides the passive
reabsorption of water from the tubular lumen towards the
interstice to balance the difference in osmolarity; water flow can
follow both a paracellular way and a transcellular way, as
some tiny little spaces exist between cells of the lining epithelium
but also the membrane of these cells is permeable to water.
In the distal portions of the tubules paracellular permeability is
very low and therefore epithelium is impermeable to water. In
particular the ascending portion of Henle’s loop and the DCT are completely impermeable to water,
while the connecting and collecting tubules allow water passage highly regulated through specific protein
pores called aquaporins.
114 Body At Work II
