The kidney is the organ that performs the function of maintaining the
correct volume and composition values of the plasma (homeostasis), and at
the same time, of eliminating metabolites and exogenous substances,
retaining the solutes necessary for the body.
These control functions are performed by regulating the elimination of water
and solutes from the body through the urine. The fundamental mechanism is
that of a two-stage filter, which allows the passage of water and solutes in
the pre-urine through a little specific filtration of the plasma (only cells
and macromolecules are retained) and the subsequent reabsorption and / or
secretion, selective and controlled, of solutes, followed in a finely
regulated way by water.
The kidney is made up of functional units called "nephrons", whose
anatomical structure reflects this two-stage way of working:
a) each nephron is formed by a capillary ball (glomerulus), which operates
the filtration,
b) from a tubule, along which the transport processes that allow the
reabsorption or selective secretion of solutes take place.
The fundamental engine of all transport systems is the sodium-potassium pump
of the tubule cells, which extrudes sodium ions (Na +) towards the
interstitium
In summary, the kidney performs the following functions:
• Filter function
Elimination from the blood and excretion
with the urine of catabolites (urea, creatinine, uric acid, final products
degradation of hemoglobin, metabolites, hormones) and exogenous substances
(drugs, food additives)
• Homeostatic function
Water balance regulation
Electrolyte balance regulation
Acid-base balance regulation
Blood pressure regulation
• Hormonal function
Production of hormones involved in:
Erythropoiesis (erythropoietin)
Ca2 + metabolism (1,25-dihydroxycholicalciferol, active form vitamin D)
Blood pressure and blood flow regulation (renin)
Gluconeogenesis
The kidney is a parenchymatous organ characterized by a rather complex
anatomical structure that reflects a refined functional organization.
Basically, it consists of two distinct regions:
- a cortical region, in which the arterial blood forms small capillary balls
(glomeruli), where the blood itself is filtered and the liquid obtained is
collected in the Bowman's capsule which envelops them and initiates the
tubules; convolutions of the tubules themselves are observed between the
glomeruli, before they continue into the medulla (proximal convoluted
tubule) and return from the medulla (distal convoluted tubule);
- a medullary region, made up of lobes (pyramids) in which run parallel: the
tubules, which descend to variable depth, form a loop (loop of Henle) and go
up to the cortex; the tubules and the collecting ducts, which collect the
contents of the distal contorted tubules and, crossing the medulla, convey
it into the calyxes of the renal pelvis; the vessels that sink parallel to
the tubules in the medulla and rise again (vasa recto).
The nephrons are divided into:
• Cortical nephrons: represent 85% of all nephrons. They are characterized
by a smaller renal corpuscle - located in the peripheral part of the cortex
- and a shorter tubule.
• Juxtamedullary nephrons (= close to the medulla): they are provided with a
more voluminous renal corpuscle located near the medulla and a much longer
tubule. Compared to the previous ones, they have an efferent arteriole that
forms not only a capillary network around the tubules, but also a series of
vascular loops (vasa recta) that descend into the medulla, surround the
collecting ducts and the ascending tracts of the loop of Henle.
These vessels are very important because, in addition to allowing the blood
to return to the cortex, they supply oxygen and nutrients to the tubular
segments, transport the substances that must be secreted to the tubules, and
bring back into the general circulation the water and solutes that must be
reabsorbed and participate in the mechanism of urine concentration /
dilution.
The vascularization of the kidney has some particularly relevant
characteristics. Arterial blood enters through the interlobar arteries and
is distributed through the arcuate arteries that run between the cortex and
medulla.
The spraying of the two portions, cortical and medullary, is anatomically
and functionally very different. Towards the cortex, arteries branch off
from the arcuate arteries - radial cortical or lobular arteries that give
rise to an arteriole for each glomerulus.
An afferent arteriole reaches the glomerulus, exits as an efferent arteriole
and forms a peritubular capillary network from which the blood flows into
lobular veins, which return to the arcuate veins. Towards the medulla, the
vascular system is much simpler, consisting of vessels that descend radially
along the pyramids and rise (vasa recta). It is important to note that
efferent arterioles have different characteristics than normal arterioles.
In fact, leaving the glomerular filtration process, they have a reduced
hydrostatic pressure and, having lost water and solutes, an increased
concentration of proteins (high oncotic pressure): both of these factors
tend to favor the massive reabsorption of water and solutes. . Since the
efferent arterioles of the juxtamedullary glomeruli, instead of giving rise
to the rich peritubular network, deepen into the medulla like the vasa
recta, it should be borne in mind that these spurious vasa recta will have
different exchange characteristics compared to the true vasa recta, which
are generated directly from arcuate arteries without having passed through
glomeruli (and therefore have higher hydrostatic pressure and the same
oncotic pressure as plasma).
Each glomerulus, with its own tubule, constitutes a relatively independent
functional unit, which is called the nephron. Blood arrives at the nephron
through the afferent arteriole and leaves the glomerulus through an efferent
arteriole.
The liquid filtered by the glomerulus passes through the proximal convoluted
tubule, along the loop of Henle
- that for the more superficial (cortical) nephrons it does not
significantly enter the medullary region, while for the deeper ones (iuxtamidollari)
it almost reaches the apex of the renal pyramid (papilla) and therefore the
distal convolutions of the tubule, before being collected in the collector
tubule which introduces it into the collector ducts to bring it to the
papillary outlet.
The peritubular capillary network irrigates the parenchyma of the cortical,
wrapping the whole loop of the cortical nephrons; for the juxtamedullary
nephrons, on the other hand, both the tubular loop and the vessels run
straight and parallel in a radial direction along the axis of the medullary
pyramids: this is essential to favor the maintenance of an osmotic gradient
in the interstitium, through the exchange mechanism counter-current.
The kidney functions as a two-stage filter:
- a molecular filter completely retains blood cells and macromolecules
(proteins weighing more than 70 kDa) and slows the passage of molecules
weighing between 10 and 70 kDa;
- ion translocation and cotransport or antiport systems allow the
reabsorption of about 97% of the filtered solutes. These transports are
actively regulated and this constitutes the main modality of regulation of
renal function.
The water follows passively, but in its turn regulated, so that the
osmolality of the urine can vary from a value below 100 to a value above
1,500 mOsm / l, for a normal value of about 1,000 mOsm / l ( versus about
300 mOsm / l for plasma).
The efficiency of such an organization is evident, with respect to a
selective elimination of all unwanted substances from the plasma, which
would require an enormous number of specific transport mechanisms and would
make it impossible to eliminate unexpected exogenous substances.
Conversely, non-selective filtration, followed by reabsorption of
electrolytes and water, leaves all the hydrophilic solutes not actively
reabsorbed in the tubule (the lipolyl solutes freely cross the membranes and
passively follow the reabsorption of water).
It will therefore be sufficient to make the metabolites and exogenous
substances hydrophilic, so that they remain trapped in the tubule, which
must be eliminated (note that liver metabolism generally proceeds in this
direction), and to possess adequate transport systems to reabsorb the
hydrophilic substances that they must not be lost.
The functioning mechanisms of the kidney allow to regulate:
- the volume of body fluids; since water passively follows, the amount of
solutes (and in particular sodium - Na + -, the most abundant species
eliminated by the kidney determines the amount of fluid eliminated;
diuretics interfere with one or the other of the reabsorption mechanisms of
Na + and are used to eliminate liquids, reduce blood pressure or reduce the
load on the heart.
The renal glomerulus is the specialized structure for plasma filtration: it
consists of an arterial capillary ball wrapped in a capsule (Bowman's
capsule) from which the tubule begins. The renal cortex contains
approximately one million glomeruli.
The glomerular filter allows the passage of solutes only and a partial
diffusion of macromolecules (reduced if negatively charged) and of small:
cine, while it prevents the filtration of proteins larger than albumin and
blood cells. The glomerular filtration rate VFG, approximately 125 ml / min)
depends on the capillary pressure in the glomerulus and on the size of the
interstices between the pedicels of the mesangial cells that line the
glomerular capillary. However, it is also influenced by glomerular blood
flow: if this is slowed down, filtration produces a significant
concentration of proteins, which opposes further filtration by oncotic
pressure.
The tone of the glomerular arterioles (afferent and efferent) is finely
self-regulated by internal reflexes in the kidney, with the result that the
perfusion pressure and the VFG remain virtually constant over a wide range
of blood pressure values (80-180 mmHg); nevertheless, the urinary volume
changes greatly in response to pressure variations, thanks to marked
alterations in the tubular reabsorption processes.
Renal excretion of substances is operationally expressed in terms of
clearance. A substance filtered in the glomerulus and not reabsorbed or
excreted in the tubule is eliminated with the speed with which it is
filtered: this corresponds to cleaning up a corresponding amount of plasma
(clearance = 125 ml min). Reabsorbed substances have lower clearance (up to
zero, if completely reabsorbed), while actively secreted substances can have
much higher clearances (up to a value corresponding to renal plasma flow, if
completely secreted). The measurement of the clearance of substances known
to be renal behavior (e.g., inu-line, filtered only; PAI, filtered and
actively secreted) provides an estimate of important renal parameters
(filtration rate, renal plasma flow useful in clinical evaluation renal
function.
Blood filtration in the kidney takes place in corpuscles (Malpighi's),
located in the renal cortex, which consist of a capillary ball (arterial
glomerulus) which invaginates in Bowman's capsule generating, between the
parietal and visceral epithelial sheet of the capsule, a space (capsular
chamber) that collects the filtrate. The visceral leaflet of the capsular
epithelium is formed by podocytes that interdigitate their pedicels,
creating a porous membrane whose pores have a diameter of about 5 nm.
Between the podocytes and the capillary endothelium, thin and broadly
fenestrated (pores of 50-100 nm), there is a basement membrane which helps
to define the properties of the glomerular filter. Ultrafiltration barrier
(blood / urine barrier). It consists of the fenestrated endothelium of the
glomerular capillaries, the basement membrane and the interdigitations of
the podocytes that form the visceral sheet of the glomerular capsule.
Podocytes appear as star-like elements, with numerous extensions (primary
processes) that embrace the glomerular capillaries. The primary processes
branch giving rise to secondary processes (pedicels or terminal feet) which
adhere to the outer surface of the basement membrane of the glomerular
capillaries. Filtration holes or slits are established between the
contiguous pedicels, closed by diaphragms (diaphragms of the filtration
holes or membranes of the slits). The ultrafiltration barrier of which the
basement membrane is the thickest and most discontinuous layer, allows the
passage of water, ions and crystalloids.
Functions and constitution of the glomerulus filtration membrane
Allows passage of H2O + low molecular weight solutes (65000, <69 kDa);
It exerts a selective action as a function of the size and electric charge
of the molecules. Filtration:
• free molecules radius <20Å (-5 KDa) • variable molecules radius 20-42Å •
absent molecules radius> 42Å (-70 KDa).
Formed by:
• Fenestrated capillary endothelium (pores 50-100 nm) covered with fixed
negative charges, which hinder the passage of plasma proteins (negative
charge).
• Basal membrane formed by collagen and proteoglycans (negatively charged)
is an effective barrier to the passage of plasma proteins.
• Visceral layer of Bowman's capsule (podocytes, with terminal processes,
pedicels, which form slit pores (4-14 nm, closed by protein structure,
filtration diaphragm, adjustable). Negatively charged glycoproteins are
present.
As it passes through the glomerulus, approximately one fifth of the
plasma is filtered into the capsule. By the anatomical features of the
glomerular filter, all dissolved substances in plasma with a molecular mass of
less than 5 kDa (the mass of a small protein of about 50 amino acids) pass.
Between 5 and 70 kDa (molecular radius between 1 and 4 nm) the filtration is
partial, while above 70 kDa the filtration becomes null (molecular filter). To
quantify this behavior, a glomerular filtration coefficient (SG) is defined
which represents the concentration ratio between filtrate and plasma, between 0
and 1, which depends not only on the size, but also to a good extent, for
molecules with size similar to the diameter of the pore, from the
characteristics of the basement membrane; this, in fact, is rich in fixed
negative charges (proteoglycans and acid mucopolysaccharides), and tends to
reject the negatively charged molecules, thus hindering the passage of the
electrical filter anions).
The relationship between molecular size, charge and SG was studied using dextran
polymers, demonstrating that the filtration of macromolecules with a radius
between 18 and 36 A depends on their charge. If albumin, the smallest plasma
protein (radius = 35 A), were neutral, it would filter significantly at the
glomerular level resulting in severe hypoalbuminemia. However, the plasma
proteins, at physiological pH, are deprotonated and therefore behave like
polyanionic dextrans, making the filtration of albumin and, even more so, of the
other plasma proteins of higher dimensions practically nil. If, however, due to
pathological processes, the basement membrane loses its negative charges, the
selectivity based on the charge is lost with consequent filtration of plasma
albumin and albuminuria.
It should also be borne in mind that the failure of proteins such as albumin and
globulins to pass through the glomerular filter means that all molecules, even
small ones, which are bound to plasma proteins, pass only in relation to the
free share, i.e. the filtrate will contain them in concentration at most equal
not to the plasma concentration, but to that of the non-protein bound fraction
(when SG is equal to 1).
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