Maintenance of the Body
endocrine systems maintain blood pressure. In extreme changes
of blood pressure (mean arterial pressure less than 80 or greater
than 180 mm Hg), extrinsic controls take precedence over in-
trinsic controls in an eﬀort to prevent damage to the brain and
other crucial organs.
GFR can be controlled by changing a single variable—
glomerular hydrostatic pressure. All major control mechanisms
act primarily to change this one variable. If the glomerular
hydrostatic pressure rises, NFP rises and so does GFR. If the
glomerular hydrostatic pressure falls by as little as 18%, GFR
drops to zero. Clearly hydrostatic pressure in the glomerulus
must be tightly controlled. Let’s see how the intrinsic and extrin-
sic mechanisms accomplish this feat.
Intrinsic Controls: Renal Autoregulation
By adjusting its
own resistance to blood ﬂow, a process called
, the kidney can maintain a nearly constant GFR de-
spite ﬂuctuations in systemic arterial blood pressure. Renal
autoregulation uses two diﬀerent mechanisms: (1) a
and (2) a
tubuloglomerular feedback mechanism
, le± side).
ik) reﬂects a property of vascular smooth muscle—it
contracts when stretched and relaxes when not stretched.
Rising systemic blood pressure stretches vascular smooth
muscle in the arteriolar walls, causing the aﬀerent arte-
rioles to constrict. Tis constriction restricts blood ﬂow
into the glomerulus and prevents glomerular blood pres-
sure from rising to damaging levels. Declining systemic
blood pressure causes dilation of aﬀerent arterioles and
raises glomerular hydrostatic pressure. Both responses
help maintain normal NFP and GFR.
Tubuloglomerular feedback mechanism.
tion by the ﬂow-dependent
is “directed” by the
macula densa cells
(see Figure 25.8). Tese cells, lo-
cated in the walls of the ascending limb of the nephron
loop, respond to ﬁltrate NaCl concentration (which varies
directly with ﬁltrate ﬂow rate). When GFR increases, there
is not enough time for reabsorption and the concentration
of NaCl in the ﬁltrate remains high. Te macula densa cells
respond to high levels of NaCl in ﬁltrate by releasing vaso-
constrictor chemicals (A²P and others) that cause intense
constriction of the aﬀerent arteriole, reducing blood ﬂow
into the glomerulus. Tis drop in blood ﬂow decreases the
NFP and GFR, slowing the ﬂow of ﬁltrate and allowing
more time for ﬁltrate processing (NaCl reabsorption).
On the other hand, the low NaCl concentration of
slowly ﬂowing ﬁltrate inhibits A²P release from macula
densa cells, causing vasodilation of the aﬀerent arterioles
(Figure 25.12). Tis allows more blood to ﬂow into the
glomerulus, thus increasing NFP and GFR.
Autoregulatory mechanisms maintain a relatively constant
GFR over an arterial pressure range from about 80 to 180 mm
Hg. Consequently, normal day-to-day changes in our blood
pressure (such as during exercise, sleep, or changes in posture)
²wo inward forces inhibit ﬁltrate formation
by opposing HP
in the capsular space (HP
pressure exerted by ﬁltrate in the glomerular capsule. HP
is much higher than hydrostatic pressure surrounding most
capillaries because ﬁltrate is conﬁned in a small space with a
colloid osmotic pressure
in glomerular capillaries
is the pressure exerted by the proteins in the blood.
As shown in Figure 25.11, the above pressures determine
net ﬁltration pressure (NFP)
. NFP largely determines the
glomerular ﬁltration rate, which we consider next.
Glomerular Filtration Rate (GFR)
glomerular ﬁltration rate
is the volume of ﬁltrate formed
each minute by the combined activity of all 2 million glomeruli
of the kidneys. GFR is directly proportional to each of the fol-
Net ﬁltration pressure.
NFP is the main controllable fac-
tor. Of the pressures determining NFP, the most important
is hydrostatic pressure in the glomerulus. Tis pressure can
be controlled by changing the diameter of the aﬀerent (and
sometimes the eﬀerent) arterioles, as we will see shortly.
Total surface area available for ﬁltration.
illaries have a huge surface area (collectively equal to the
surface area of the skin). Glomerular mesangial cells sur-
rounding these capillaries can ﬁne-tune GFR by contracting
to adjust the total surface area available for ﬁltration.
Filtration membrane permeability.
are thousands of times more permeable than other capillar-
ies because of their fenestrations.
Te huge surface area and high permeability of the ﬁltration
membrane explain how the relatively modest 10 mm Hg NFP
can produce huge amounts of ﬁltrate. Furthermore, the NFP in
the glomerulus favors ﬁltration over the entire length of the cap-
illary, unlike other capillary beds where ﬁltration occurs only at
the arteriolar end and reabsorption occurs at the venous end. As
a result, the adult kidneys produce about 180 L of ﬁltrate daily,
in contrast to the 2 to 4 L formed daily by all other capillary beds
combined. Tis 180 L of ﬁltrate per day translates to the normal
GFR of 120–125 ml/min.
Regulation of Glomerular Filtration
GFR is tightly regulated to serve two crucial and sometimes
opposing needs. Te kidneys need a relatively constant GFR to
make ﬁltrate and do their job maintaining extracellular homeo-
stasis. On the other hand, the body as a whole needs a constant
blood pressure, and this is closely tied to GFR in the following
way: Assuming nothing else changes, an increase in GFR in-
creases urine output, which reduces blood volume and blood
pressure. Te opposite holds true for a decrease in GFR.
²wo types of controls serve these two diﬀerent needs.
) act locally within the kidney
to maintain GFR, while
by the nervous and