RENAL PATHOPHYSIOLOGY
GLOMERULOPATHIES
RENAL PHYSIOLOGY
KIDNEY FUNCTIONS AND GFR
The kidney has multiple functions, which are excretion of waste products, acid-base balance,
electrolyte balance, regulation of ECF volume, and regulation of BP. It is also an electro-mechanical
filter, and this function is performed by the renal glomerulus.
The second function is performed by the renal tubule, which
modify the content of the ultrafiltrate previously collected by
the glomerulus. The modification is mediated by the protein
channels present in the renal epithelial cells that form the
renal tubule. These channels can either reabsorb or secrete
biochemical elements, determining the urinary content.
The volume of blood that is filtered every day is 180L, while
the volume of urine that is produced is of 1.2-1.5L; this means
that about 99% of fluid is reabsorbed by the kidney every day.
The glomerular filtration rate (GFR) refers to the rate of
filtration achieved by the glomerulus. The main requirement
for it is to have a good blood perfusion, which ensures enough pressure to exert in the glomerulus.
The GFR is given by the difference between the hydrostatic glomerular pressure (PG), the osmotic
glomerular pressure (G), and the hydrostatic capillary pressure (Pc). Therefore, it is determined by
the Sterling forces. This parameter is also used to assess the renal function of patients.
GLOMERULAR BASEMENT MEMBRANE (GBM)
The glomerulus presents a specific functional anatomy, which is required for its filtering function. The
filtration, as said before, is determined by the Starling forces, which in this case are related to the
capillary pressures and the Bowman space pressures. In this case,
the capillary permeability is not determined primarily by the
epithelium since it is fenestrated, but by the diaphragmatic slits of
the podocytes.
An important part of the glomerulus, is the glomerular barrier
membrane (GBM), which is the site in which the filtration occurs. It
is composed of three elements, which are:
• Endothelium: it is a fenestrated endothelium, which
theoretically allows macromolecules (e. g. albumin) to pass
through it.
• Basement membrane: it is made of ECM proteins, such as
collagen type IV and proteoglycans, which avoid the
movement of macromolecules towards the Bowman space;
moreover, this membrane is negatively charged, and therefore there is both a mechanical and
an electrical opposition of the passage of macromolecules; for that reason, the glomerulus is
considered an electro-mechanical filter; this membrane is composed of three parts, which
are:
Lamina rara interna.
Lamina densa.
Lamina rara externa.
• Podocytes: they are epithelial cells that present
several protrusions called foot processes; these
processes interact through diaphragmatic
openings, called filtration slits, which has a
, diameter of 8-9nm; only substance smaller than that dimension can pass through them.
DETERMINANTS OF THE RENAL BLOOD FLOW
The determinant of the GFR is mainly the blood pressure; it must be constant to allow the correct
filtration of blood. Either higher or lower pressures will cause changes in the GFR. The regulation of
the renal blood pressure allows to maintain
constant the GFR, within a physiological range
(80-170mmHg). The regulation can be of two
types, which are:
• Autoregulation: it is mediated directly
by kidney, and it can be of two types,
which are:
Myogenic response: it is the
fastest, and it is mediated by
mechanoreceptors that sense
changes in BP; when high BP is
present in the afferent
arteriole, the
mechanoreceptors cause a
vasoconstriction, resulting in a
reduction of GFR.
Tubuloglomerular response: it
is the slower response, which
senses changes in the Na+
concentration in the renal
tubule (macula densa); when
high concentration of sodium
are present, the macula densa
causes a vasoconstriction of the afferent arteriole, resulting in a reduced GFR.
• Sympathetic response: it is mediated by baroreceptors, which can sense the decrease in the
blood pressure, and via a vasomotor centre response increase the release of epinephrine and
norepinephrine, thus causing a vasoconstriction of the efferent arterioles, thus maintaining
constant the GFR.
NEPHROTIC VS NEPHRITIC SYNDROMES
NEPHROTIC SYNDROME
The filtration in the glomerulus can be affected by problems that occur in one of the three layers of
the GBM. For instance, antibodies and immune complexes can get stacked in the basement
membrane, resulting in glomerulonephritis. There are
also antibodies that can recognise components of the
basement membrane, resulting in its degradation (e. g.
SLE, Goodpasture syndrome). Finally, another
mechanism can be complement activation, which
causes the basement membrane degradation.
The diseases affecting the glomerulus are known as
glomerulopathies, and they can be divided into two
types, which are the nephrotic and the nephritic
syndromes.
The nephrotic syndrome is caused by the inability of the
glomeruli to keep plasma protein within the blood
lumen. It is caused by a loss of permeability of
GLOMERULOPATHIES
RENAL PHYSIOLOGY
KIDNEY FUNCTIONS AND GFR
The kidney has multiple functions, which are excretion of waste products, acid-base balance,
electrolyte balance, regulation of ECF volume, and regulation of BP. It is also an electro-mechanical
filter, and this function is performed by the renal glomerulus.
The second function is performed by the renal tubule, which
modify the content of the ultrafiltrate previously collected by
the glomerulus. The modification is mediated by the protein
channels present in the renal epithelial cells that form the
renal tubule. These channels can either reabsorb or secrete
biochemical elements, determining the urinary content.
The volume of blood that is filtered every day is 180L, while
the volume of urine that is produced is of 1.2-1.5L; this means
that about 99% of fluid is reabsorbed by the kidney every day.
The glomerular filtration rate (GFR) refers to the rate of
filtration achieved by the glomerulus. The main requirement
for it is to have a good blood perfusion, which ensures enough pressure to exert in the glomerulus.
The GFR is given by the difference between the hydrostatic glomerular pressure (PG), the osmotic
glomerular pressure (G), and the hydrostatic capillary pressure (Pc). Therefore, it is determined by
the Sterling forces. This parameter is also used to assess the renal function of patients.
GLOMERULAR BASEMENT MEMBRANE (GBM)
The glomerulus presents a specific functional anatomy, which is required for its filtering function. The
filtration, as said before, is determined by the Starling forces, which in this case are related to the
capillary pressures and the Bowman space pressures. In this case,
the capillary permeability is not determined primarily by the
epithelium since it is fenestrated, but by the diaphragmatic slits of
the podocytes.
An important part of the glomerulus, is the glomerular barrier
membrane (GBM), which is the site in which the filtration occurs. It
is composed of three elements, which are:
• Endothelium: it is a fenestrated endothelium, which
theoretically allows macromolecules (e. g. albumin) to pass
through it.
• Basement membrane: it is made of ECM proteins, such as
collagen type IV and proteoglycans, which avoid the
movement of macromolecules towards the Bowman space;
moreover, this membrane is negatively charged, and therefore there is both a mechanical and
an electrical opposition of the passage of macromolecules; for that reason, the glomerulus is
considered an electro-mechanical filter; this membrane is composed of three parts, which
are:
Lamina rara interna.
Lamina densa.
Lamina rara externa.
• Podocytes: they are epithelial cells that present
several protrusions called foot processes; these
processes interact through diaphragmatic
openings, called filtration slits, which has a
, diameter of 8-9nm; only substance smaller than that dimension can pass through them.
DETERMINANTS OF THE RENAL BLOOD FLOW
The determinant of the GFR is mainly the blood pressure; it must be constant to allow the correct
filtration of blood. Either higher or lower pressures will cause changes in the GFR. The regulation of
the renal blood pressure allows to maintain
constant the GFR, within a physiological range
(80-170mmHg). The regulation can be of two
types, which are:
• Autoregulation: it is mediated directly
by kidney, and it can be of two types,
which are:
Myogenic response: it is the
fastest, and it is mediated by
mechanoreceptors that sense
changes in BP; when high BP is
present in the afferent
arteriole, the
mechanoreceptors cause a
vasoconstriction, resulting in a
reduction of GFR.
Tubuloglomerular response: it
is the slower response, which
senses changes in the Na+
concentration in the renal
tubule (macula densa); when
high concentration of sodium
are present, the macula densa
causes a vasoconstriction of the afferent arteriole, resulting in a reduced GFR.
• Sympathetic response: it is mediated by baroreceptors, which can sense the decrease in the
blood pressure, and via a vasomotor centre response increase the release of epinephrine and
norepinephrine, thus causing a vasoconstriction of the efferent arterioles, thus maintaining
constant the GFR.
NEPHROTIC VS NEPHRITIC SYNDROMES
NEPHROTIC SYNDROME
The filtration in the glomerulus can be affected by problems that occur in one of the three layers of
the GBM. For instance, antibodies and immune complexes can get stacked in the basement
membrane, resulting in glomerulonephritis. There are
also antibodies that can recognise components of the
basement membrane, resulting in its degradation (e. g.
SLE, Goodpasture syndrome). Finally, another
mechanism can be complement activation, which
causes the basement membrane degradation.
The diseases affecting the glomerulus are known as
glomerulopathies, and they can be divided into two
types, which are the nephrotic and the nephritic
syndromes.
The nephrotic syndrome is caused by the inability of the
glomeruli to keep plasma protein within the blood
lumen. It is caused by a loss of permeability of
