RENAL BLOOD FLOW & GLOMERULAR FILTRATION
The concept of clearance is frequently
used in mea-surements of RBF and the glomerular filtration rate (GFR). The
renal clearance of a substance is defined as the volume of blood that is
completely cleared of that substance per unit of time (usually, per minute).
Renal plasma flow
(RPF) is most commonly mea-sured by p-aminohippurate
(PAH) clearance. PAH at low plasma concentrations can be assumed to be
completely cleared from plasma by f ltration and secretion in one passage
through the kidneys. Consequently,
where [PAH]U= urinary concentration
of PAH and [PAH]P= plasma PAH
concentration.
If the hematocrit
(measured as a decimal rather than as a percent) is known, then
RPF and RBF are normally about 660 and 1200 mL/min, respectively.
The GFR, the volume of fluid filtered
from the glo-merular capillaries into Bowman’s capsule per unit time, is
normally about 20% of RPF. Clearance of inulin, a fructose polysaccharide that
is completely filtered but is neither secreted nor reabsorbed, is a good
measure of GFR. Normal values for GFR are about 120 ± 25 mL/min in men and 95 ± 20 mL/ min in women. Although less accurate than
measur-ing inulin clearance, creatinine clearance is a much more practical
measurement of GFR . Creatinine clearance tends to overestimate GFR because
some creatinine is normally secreted by renal tubules. Creatinine is a product
of phospho-creatine breakdown in muscle. Creatinine clearance is calculated as
follows:
where [creatinine]U= creatinine concentration in urine and [creatinine]P= creatinine
concentration in plasma.
The ratio of GFR to RPF is called the filtrationfraction (FF) and is normally
20%. GFR is dependenton the relative tones of both the afferent and efferent
arterioles (see above). Afferent arteriolar dilation or efferent arteriolar
vasoconstriction can increase the and maintain GFR, even when RPF decreases.
Afferent arteriolar tone appears to be responsible for maintaining a relatively
constant GFR over a wide range of blood pressures.
Regulation of RBF represents a complex interplay between
intrinsic autoregulation, tubuloglomerular balance, and hormonal and neuronal
influences.
Autoregulation of RBF normally occurs
between mean arterial blood pressures of 80and 180 mm Hg and is principally due
to intrinsic myogenic responses of the afferent glomerular arte-rioles to blood
pressure changes. Within these lim-its, RBF (and GFR) can be kept relatively
constant by afferent arteriolar vasoconstriction or vasodilation. Outside the
autoregulation limits, RBF becomes pressure dependent. Glomerular filtration
generally ceases when mean systemic arterial pressure is less than 40–50 mm Hg.
Tubuloglomerular
feedback plays an
important rolein maintaining constant GFR over a wide range of perfusion
pressures. Increased tubular flow tends to result in reduced GFR; conversely,
decreased tubular flow tends to result in increased GFR. Although the mechanism
is poorly understood, the macula densa appears to be responsible for
tubuloglomerular feed-back by inducing reflex changes in afferent arteriolar
tone and possibly glomerular capillary permeability. Angiotensin II probably
plays a permissive role in this mechanism. Local release of adenosine, which
occurs in response to volume expansion, may inhibit renin release and dilate
the afferent arteriole.
Increases
in afferent glomerular arteriolar pressure stimulate renin release and
formation of angiotensinAngiotensin II causes generalized arterial
vaso-constriction and secondarily reduces RBF. Both afferent and efferent
glomerular arterioles are con-stricted, but because the efferent arteriole is
smaller, its resistance becomes greater than that of the affer-ent arteriole;
GFR therefore tends to be relatively preserved. Very high levels of angiotensin
II con-strict both arterioles and can markedly decrease GFR. Adrenal
catecholamines (epinephrine and norepinephrine) directly and preferentially
increase afferent arteriolar tone but usually do not cause marked decreases in
GFR because these agents also increase renin release and angiotensin II
formation. Relative preservation of GFR during increased aldo-sterone or
catecholamine secretion appears at least partly to be mediated by
angiotensin-induced pros-taglandin synthesis because it can be blocked by
inhibitors of prostaglandin synthesis such as nonste- roidal antiinflammatory
drugs (NSAIDs). Renal synthesis of vasodilating prostaglandins
(PGD2, PGE2,
and PGI2) is an important protective mechanism during periods of
systemic hypotension and renal ischemia.
ANP
is released from atrial myocytes in response to atrial distention. ANP is a
direct smooth muscle dilator and antagonizes the vasoconstric-tive action of
norepinephrine and angiotensin II. It preferentially dilates the afferent
glomerular arteri-ole, constricts the efferent glomerular arteriole, and
relaxes mesangial cells, effectively increasing GFR . ANP also inhibits both
the release of renin and angiotensin-induced secretion of aldo-sterone, and
antagonizes the action of aldosterone in the distal and collecting tubules.
Sympathetic outflow from the spinal cord
at the level of T4–L1 reaches the kidneys via the celiac and renal plexuses.
Sympathetic nerves innervate the juxtaglo-merular apparatus (β1) as well as the renal vasculature (α1). This innervation is largely
responsible for stress-induced reductions in RBF (below). α1-Adrenergic receptors enhance sodium
reabsorption in proximal tubules, whereas α2 receptors decrease such reabsorp-tion and promote
water excretion. Dopamine and fenoldopam dilate afferent and efferent
arterioles via D1-receptor activation. Unlike dopa-mine, fenoldopam
is selective for the D1-receptor. Fenoldopam and low-dose
dopamine infusion can at least partially reverse norepinephrine-induced renal
vasoconstriction. Activation of D2-receptors on pre-synaptic
postganglionic sympathetic neurons can also vasodilate arterioles through
inhibition of nor-epinephrine secretion (negative feedback). Dopamine is formed
extraneuronally in the proximal tubule cells from circulating
L-3,4-dihydroxyphenylalanine (L-dopa). Dopamine is released into the tubule
where it can bind dopaminergic receptors to reduce proxi-mal reabsorption of Na+.
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