Download Urinary Homeostasis: Homeostasis

Urinary Homeostasis: Homeostasis
Regulation of Glomerular Filtration
In a healthy body, GFR remains relatively constant even in the face of
substantial changes in arterial blood pressure. By adjusting resistance to
the flow of blood, renal autoregulation prevents significant
fluctuations in GFR when systemic arterial blood pressure rises or falls.
Two mechanisms are involved in this intrinsic control. The myogenic
mechanism results from the inherent tendency of vascular smooth
muscle to contract when stretched. This means that the diameter of
afferent arterioles changes in response to fluctuations in blood pressure.
Increasing blood pressure in the afferent arteriole stretches the smooth
muscle in the wall of the arteriole. As a result, the smooth muscle will
contract and the arteriole will vasoconstrict. This reduces the diameter
of afferent arterioles, and blood flow. Decreasing blood pressure in the
afferent arteriole removes the stretch of the smooth muscle in the wall of
the arteriole. As a result, the smooth muscle will relax and the arteriole
will vasodilate. This increases the diameter of afferent arterioles and
blood flow. In both cases, the result is a relatively stable GFR.
The second element of renal autoregulation is the tubuloglomerular
feedback mechanism The macular densa cells of the distal
convoluted tubule are part of the juxtaglomerular apparatus and are
responsible for the tubuloglomerular feedback mechanism. The macula
densa cells respond to the sodium concentration in the filtrate that flows
from the ascending limb of nephron loop into the distal convoluted
tubule. The sodium concentration in the filtrate is directly related to the
rateglomerular filtration rate (GFR). When GFR is high, there is not
enough time for reabsorption, and the filtrate will have a high sodium
concentration. The macular densa cells respond to this high sodium
concentration by releasing the vasoconstrictor adenosine, which
narrows the diameter of the afferent arterioles. Reduced blood flow
lowers the net filtration pressure and the GFR, which enhances sodium
chloride reabsorption. Conversely, when GFR is low the filtrate will have
a low sodium concentration. The release of the paracrine agent by
macula densa cells is inhibited. As a result, the afferent arterioles dilate
and increase tje blood flow into the glomerulus. The result is to increase
net filtration pressure in the glomerulus and increase GFR. This has the
opposite effect of macula densa cell activation: it increases the amount
of filtered sodium, and it reduces sodium reabsorption.
These two autoregulatory mechanisms help keep the flow of blood
through the kidneys relatively constant when mean systemic arterial
blood pressure is within a range of approximately 80 mm Hg to 180 mm
Hg. However, autoregulation cannot adjust for changes in systemic
blood pressure that are outside of this range.
Neural Regulation
The sympathetic nerve fibers that innervate renal blood vessels provide
an extrinsic regulatory mechanism for GFR. During extreme stress or
blood loss, the sympathetic nervous system must meet the needs of the
body as a whole, for example, by temporarily reducing kidney activity
and redirecting blood to other vital organs. In such situations, neural
controls override renal autoregulation. The sympathetic nerve fibers
release the neurotransmitter norepinephrine. Norepinephrine
activates alpha-adrenergic receptors on vascular smooth muscle
and causes afferent arterioles to constrict. The resulting reduced blood
flow into glomerular capillaries lowers net filtration pressure and GFR.
This decreased renal blood flow helps maintain blood volume by
reducing urine output and increasing perfusion to other body tissues.
Hormonal Regulation
Hormones also regulate GFR. One such mechanism is activated when
jutaglomerular (JG) (or granular) cells are stimulated to secrete the
enzyme renin. This enzyme begins a process that results in the
production of angiotensin II, a powerful systemic vasoconstrictor that
also constricts the afferent and efferent arterioles. Angiotensin II also
stimulated the contraction of mesangial cells resulting in a decrease in
the surface area of the glomerulus. Because renin is released when blood
pressure is low, the resulting constriction of the efferent arteriole helps
maintain net filtration pressure in the glomerular capillary and
consequently, GFR. Another hormone, atrial natriuretic peptide (ANP)
increases GFR. ANP is released when the atria of the heart is stretched,
for example, in heart failure when blood volume increases due to
sodium and water retention. ANP relaxes the mesangial cells of the
glomerulus, making more surface area available for filtration. This
increases GFR.
Glomerular Filtration Regulation
Regulation
Primary Stimulus
Mechanism/Activity Site
Effect
Renal
autoregulation
Systemic rising or
falling of arterial
blood pressure
Adjusts resistance to the
flow of blood, when
systemic arterial blood
pressure rises or falls
Prevents
significant
fluctuations
in GFR
Myogenic
mechanism
Smooth muscle fibers
in walls of afferent
arteriole are stretched
when blood pressure
increases
Contraction of smooth GFR
muscle fibers narrows decrease
lumen of afferent arterioles
Tubuloglomerular
feedback
Increased delivery of
sodium ions and
chloride ions to the
macula densa when
blood
pressure
increases
Constriction of afferent GFR
arterioles due to the release decrease
of adenosine by macula
densa cells
Vasoconstrictor
adenosine
Decreased delivery of
sodium ions and to
the macula densa
when blood pressure
drops
Dilation
of
afferent GFR increase
arterioles due to inhibition
of adenosine release by
macula densa cells
Neural regulation
Release
of
norepinephrine due to
increased activity of
renal
sympathetic
nerves
Constriction of afferent GFR
arterioles due to activation decrease
of
alpha-adrenergic
receptors and renin release
Hormone
regulation
Stimuli
cause
justaglomerular cells
to secrete renin.
Once justaglomerular cells Maintains
secrete renin, angiotensin GFR
II is produced.
Angiotensin II
Production
Constriction
of
of
afferent GFR
angiotensin II due to
decreased
blood
volume or blood
pressure
arteriole and contraction of decrease
mesangial cells
ANP
Secretion of ANP due
to stretching of atria
of heart
Capillary surface area GFR increase
available for filtration
increased due to relaxation
of mesangial cells in
glomerulus
Hormonal
Secretion
Regulation
of
Reabsorption
and
Five hormones control the absorption of water, and sodium, chloride,
and calcium ions: angiotensin II, aldosterone, antidiuretic hormone,
atrial natriuretic peptide, and parathyroid hormone.
Let’s look at each:
Angiotensin II
The renin-angiotensin-aldosterone system is stimulated when blood
volume and blood pressure decrease. A decrease in blood pressure
reduces the amount of stretch in afferent arteriole walls and stimulates
juxtaglomerular cells to release renin into the blood. Renin release is
also stimulated directly by sympathetic nerve fiber activity. Renin sets in
motion a cascade of events that leads to the production of the hormone
angiotensin II.
Angiotensin II plays three primary roles. First, it constricts afferent
arterioles, resulting in a reduction in GFR. Second, it stimulates an
exchange mechanism. This leads to an increase in the reabsorption of
water, sodium ions, and chloride ions. Finally, the hormone prompts the
adrenal cortex to secrete the hormone aldosterone.
Aldosterone
The release of aldosterone from the adrenal cortex is stimulated by the
presence of angiotensin II as well as an increased concentration of
potassium ions. Aldosterone stimulates the insertion of sodium
channels in the apical membrane and sodium/potassium pumps in the
basolateral membranes of the principal cells of the distal convoluted
tubules and the collecting ducts. The result is an increase in the
reabsorption of sodium ions. Aldosterone also increases the secretion of
potassium ions by principal cells in the collecting duct. Because of the
increased reabsorption of sodium ions, more water is reabsorbed and
blood volume is effectively increased.
Antidiuretic hormone (ADH)
Antidiuretic hormone (ADH) acts to decrease urine production by
increasing the permeability of principal cells in the late distal convoluted
tubule and the collecting duct, thus increasing facultative water
reabsorption. Without ADH, the apical membranes of principal cells are
relatively water-impermeable. ADH also stimulates the insertion of
aquaporins in the apical membrane, allowing water molecules to move
more quickly from tubular fluid into the cells and then through the
always fairly permeable basolateral membrane and into the blood. When
you are dehydrated, ADH is released, and the kidneys conserve water by
producing a small volume of very concentrated urine. ADH secretion is
controlled bv a negative feedback system. When the water
concentration of plasma and interstitial fluid decreases (i.e., when
osmolarity increases), more ADH is secreted into the blood, making
principal cells more water-permeable. This restores plasma osmolarity
towards normal.
Atrial natriuretic peptide
Atrial natriuretic peptide is released from the heart in response to large
increases in blood volume. This hormone inhibits the reabsorption of
water and sodium ions in the proximal convoluted tubule and collecting
duct. It also inhibits aldosterone and ADH secretion. The resulting
increased sodium ion excretion in urine and the increased urine output
lower blood volume and pressure.
Parathyroid hormone (PTH)
Parathyroid hormone (PTH) affects calcium and phosphate ion
reabsorption. It is released by the parathyroid glands in response to a
reduced concentration of calcium ions in the blood. PTH stimulates
increased reabsorption of calcium ions in the early distal convoluted
tubule. PTH also inhibits the reabsorption of phosphate ions in the
proximal convoluted tubule, prompting the excretion of phosphate ions
in the urine.
Hormones Involved in the Regulation of Reabsorption and
Secretion
Hormone
Stimulus
Release
for Result
Aldosterone
Increased levels of
angiotensin II and
plasma potassium
ion (K+)
Angiotensin
II
Reduced
blood Increased reabsorption of solutes
volume or reduced (including Na+) and water,
blood pressure
leading to increased blood volume
Antidiuretic
hormone
Increased
Increased facultative reabsorption
osmolarity
of of water, leading to reduced
extracellular fluid osmolarity of body fluids
or decreased blood
volume
Atrial
natriuretic
peptide
Stretching of atria Increased excretion of Na+ in
of heart
urine; increased urine output
reduces blood volume
Parathyroid
hormone
Decreased plasma Increased Ca2+ reabsorption,
calcium ion (Ca2+) leading to decreased reabsorption
level
of phosphate ions in the proximal
convoluted tubule and increased
excretion of phosphate ions in
urine
Increased secretion of K+ and
reabsorption of sodium ions
(Na+)
and
chloride
ions;
increased water reabsorption,
leading to increased blood volume