966
UNIT 4
Maintenance of the Body
25
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
renal autoregu-
lation
, the kidney can maintain a nearly constant GFR de-
spite fluctuations in systemic arterial blood pressure. Renal
autoregulation uses two different mechanisms: (1) a
myogenic
mechanism
and (2) a
tubuloglomerular feedback mechanism
(
Figure 25.12
, le± side).
1.
Myogenic mechanism.
Te
myogenic mechanism
(mi
0
o-
jen
9
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.
2.
Tubuloglomerular feedback mechanism.
Autoregula-
tion by the flow-dependent
tubuloglomerular feedback
mechanism
is “directed” by the
macula densa cells
of the
juxtaglomerular complex
(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)
Inward Pressures
²wo inward forces inhibit filtrate formation
by opposing HP
gc
.
Te
hydrostatic pressure
in the capsular space (HP
cs
)
is the
pressure exerted by filtrate in the glomerular capsule. HP
cs
is much higher than hydrostatic pressure surrounding most
capillaries because filtrate is confined in a small space with a
narrow outlet.
Te
colloid osmotic pressure
in glomerular capillaries
(OP
gc
)
is the pressure exerted by the proteins in the blood.
As shown in Figure 25.11, the above pressures determine
the
net filtration pressure (NFP)
. NFP largely determines the
glomerular filtration rate, which we consider next.
Glomerular Filtration Rate (GFR)
Te
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-
lowing factors:
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.
Glomerular cap-
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.
Glomerular capillaries
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.
Intrin-
sic controls
(
renal autoregulation
) act locally within the kidney
to maintain GFR, while
extrinsic controls
by the nervous and
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