Regulation of Salt and
Water Balance
General Considerations
• Perfusion of tissues is ensured by maintaining both a
sufficient volume of arterial blood and adequate pressure to
drive it through the capillaries
• Several factors go into maintenance of the central pressure:
1.
2.
3.
the beating of the heart
arteriolar constriction
sufficient volume of blood
• Central control exerted through the autonomic nervous
system provides the minute-to-minute adjustments to
cardiac function and arteriolar constriction that maintain
blood pressure relatively constant
• Volume is regulated largely by the endocrine system,
where volume and pressure are closely interrelated
Dr. M. Alzaharna (2014)
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General Considerations
• It is not surprising, therefore, that hormones that
play vital roles in regulating blood volume also
constrict or dilate arterioles
• Permeability of capillaries to small molecules
allows blood in the vascular compartment to
equilibrate quickly with interstitial fluid
• Water distributes freely between the vascular
compartment and the interstitial compartment
• Major determinants of this distribution are:
– the protein content of plasma (colloid osmotic
pressure), principally albumin,
– and blood pressure within the capillaries
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• The volumes of fluid
in the intracellular and
extracellular
compartments also
are determined by
their solute contents
• With a few important
exceptions in the
kidney, biological
membranes are freely
permeable to water
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Salt and Water Balance
• Blood plasma is in osmotic equilibrium with
interstitial and intracellular fluids;
– therefore regulation of plasma osmolality regulates
total body osmolality
• Because sodium is the major contributor to the
osmolality of blood, and because it is largely
excluded from the intracellular compartment,
changes in sodium balance can change both:
– the distribution of body water
– and its total volume
• Thus, homeostatic regulation of blood volume
depends on regulation of intake and excretion of
sodium as well as water
Dr. M. Alzaharna (2014)
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Salt Balance
• Salt and water balance are maintained remarkably
constant despite wide variations in intake and loss of
both sodium and water
• Intake of sodium may vary from almost none in saltpoor environments to several grams during a binge of
potato chips and pretzels
• Output is primarily in urine, but smaller losses are
also incurred in sweat and feces
• Large losses can result from excessive sweating,
vomiting, diarrhea, burns, or hemorrhage
Dr. M. Alzaharna (2014)
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Salt Balance
• The kidney is a powerful regulator of sodium
output and can preserve sodium balance even
when daily intake varies over the 4,000-fold
range between 50 mg and 200 g
Dr. M. Alzaharna (2014)
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Water Balance
• Under basal conditions the typical adult turns
over about 1.75 liters of water each day
• Most of the water originates from
– the diet in the form of solid and liquid foods,
– and the remainder is formed metabolically from
the oxidation of carbohydrate and fat
• Loss occur by:
– evaporation from the lungs and skin,
– as well as by elimination of wastes in the urine
and feces
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• So long as intake exceeds losses, balance can
be achieved by controlling excretion
• Intake, however, is a voluntary act and varies
widely
• Thirst and salt appetite are increased when
intake falls below the amount needed to
maintain balance
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• Blood volume is monitored indirectly, primarily as a function
of pressure
• The concentration of sodium, which is the principal osmolyte
of plasma and the primary determinant of blood volume, is
monitored only indirectly as a function of osmolality
• The kidney is the primary effector of regulation, and at least
four hormones are used to signal regulatory
• Adjustments:
–
–
–
–
ADH,
aldosterone,
angiotensin II,
and atrial natriuretic factor (also called atrial natriuretic peptide, ANP)
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Antidiuretic Hormone (ADH)
• ADH (AVP) is the hormone that signals the kidney to conserve
water when plasma osmolality is increased or when plasma
volume is decreased
– The name ADH describes the prompt decrease in urine volume that
follows hormone administration
– The name AVP refers to the acute increase in blood pressure seen as a
result of arteriolar constriction produced when the hormone is
administered in sufficient dosage
• Osmolality of blood plasma can be increased or decreased by
adjusting the proportion of water relative to solute that is
excreted in the urine, and thus produce reciprocal changes in
the osmolality of the urine
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Antidiuretic Effect
• The two actions of the hormone are produced
by two different G-protein coupled receptors,
V1 and V2
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Antidiuretic Effect
• Antidiuretic hormone conserves free water by
increasing collecting duct permeability to water
• Plasma membranes of most cells are permeable
to water because of the presence of specialized
proteins, called aquaporins (AQPs) that form
water channels
• ADH stimulates an exocytosis-like process in
which the AQP-2 bearing vesicles fuse with the
luminal membrane and thus insert AQP-2
• In the absence of ADH, AQP-2 is removed from
the luminal membrane by endocytosis and stored
in vesicular membranes
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Principal cells of the collecting duct
Before ADH
Dr. M. Alzaharna (2014)
After ADH
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Regulation of ADH Secretion
• Plasma osmolality
– Osmoreceptors are finely sensitive and elicit increased secretion
of ADH when the osmolality increases by as little as 1 to 2%
• Blood volume
– Changes in blood volume are sensed by receptors in both
arterial (high pressure) and venous (low pressure) sides of the
circulation
– Volume is monitored indirectly as the tension exerted on stretch
receptors
– The minimal change needed for low pressure receptors to signal
ADH secretion is a 10 to 15% reduction in volume
• As a general rule, osmolality is preferentially guarded when
volume depletion is small
• When volume loss is large, however, osmolality is sacrificed
in order to maintain the integrity of the circulation
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Dysfunctional States
• The disease state associated with a deficiency of
ADH is called diabetes insipidus and is
characterized by abundant production of dilute
urine
• Nephrogenic diabetes insipidus is the disease that
results from failure of the kidney to respond to
ADH and may result from defects in:
– the V2 receptor,
– aquaporin-2,
– or any of the regulatory proteins that govern cellular
responses to ADH
Dr. M. Alzaharna (2014)
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Dysfunctional States
• In the syndrome of inappropriate secretion of
ADH , ADH secretion is increased above
baseline despite low plasma osmolality
• Death may result from a profound dilution of
plasma electrolytes because of excessive
reabsorption of free water
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The Renin-Angiotensin-Aldosterone
System
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Renin Secretion
• Renin is secreted by an exocytotic process that is
activated in response to a decrease in blood volume
• Three different, but related inputs signal increased
secretion of renin:
– Juxtaglomerular cells are richly innervated by sympathetic
nerve fibers which are activated reflexly by a decrease in
arterial pressure
– Blood pressure (volume) also is sensed as tension exerted
on the smooth muscle cells of the afferent glomerular
arterioles
– Decreased glomerular filtration, decreases the rate of
sodium chloride delivery to the distal convoluted tubules
also results in increased renin secretion
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Actions of Angiotensin II
• Angiotensin II is the primary signal for
increased aldosterone secretion by adrenal
glomerulosa cells
• Actions on the kidney
– By constricting renovascular smooth muscle it
increases vascular resistance in the kidney and
hence decreases renal blood flow and glomerular
filtration
– Therefore, by decreasing glomerular filtration,
angiotensin II decreases sodium and water
excretion
Dr. M. Alzaharna (2014)
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Actions of Angiotensin II
• Cardiovascular effects
– Stimulation of angiotensin II receptors in vascular
smooth muscle results in increased intracellular
calcium concentrations and sustained vasoconstriction
– Acts directly on cardiac myocytes to increase calcium
influx and therefore cardiac contractility
• Central nervous system effects
– Angiotensin II, acting both as a hormone and as a
neurotransmitter, stimulates thirst, appetite for
sodium, and secretion of ADH through actions exerted
on the hypothalamus
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Regulation of
the ReninAngiotensin
Aldosterone
System
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