Briefly discuss the role of antidiuretic hormone and of thirst sensation
in the maintenance of body fluid osmolality.
Outline:
·
Definition of body fluid osmolality
·
Importance of maintaining body fluid osmolality
·
Control of ADH secretion
·
ADH actions on the kidneys
·
Thirst sensation
Essay:
The human body is composed of 70% water and most of it is found in the
plasma and interstitial spaces as a solution containing various ions and
solutes. These particles exert an osmotic pressure within the extracellular
fluid which determines the direction of flow of water between the cellular and
extracellular compartments. One osmole is 1 gram molecular weight of undissolved
solute. Osmolality is the number of osmoles per kilogram of solvent.
Because of its abundance, Na+ is the major determinant of the
osmolality of the ECF. The osmolality of plasma and thus of body fluids is
estimated at 290 mOsm/kg H2O. It is important to maintain the body
fluid osmolality at a relatively constant level as any major deviation from it
will disrupt cellular function. In the clinical setting, hypo-osmolality shifts
water into cells, and this process results in cell swelling. Symptoms associated
with hypo-osmolality are related primarily to swelling of brain cells, leading
to alteration of neurologic function, thereby causing nausea, malaise, headache,
confusion, lethargy, seizures, and coma. When plasma osmolality is increased,
water is lost from cells. The symptoms of an increase in plasma osmolality are
also primarily neurologic, and they include lethargy, weakness, seizures and
even death.
Antidiuretic hormone (ADH), or vasopressin, acts on the kidneys to
regulate the volume and osmolality of the urine. ADH is a small peptide nine
amino acids in length. It is synthesized by neuroendocrine cells located within
the supraoptic and paraventricular nuclei of the hypothalamus. The synthesized
hormone is packaged in granules, which are transported down the axon of the cell
and then stored in the nerve terminals located in the neurohypophysis. The
physiological regulators of ADH secretion are the osmolality of the body fluids
and the volume and pressure of the vascular system.
A change in the body fluid osmolality is the primary regulator of ADH
secretion. Changes in osmolality as small as 1% are sufficient to significantly
alter ADH secretion. The osmoreceptors in the hypothalamus sense changes in body
fluid osmolality by either shrinking or swelling. When the effective osmolality
of the body fluids increases, osmoreceptors send signals to the ADH synthesizing
cells in the hypothalamus, and ADH secretion is stimulated. Conversely, when the
effective osmolality of the body fluid is reduced, secretion is inhibited. The
set point of the system is defined as the plasma osmolality value at which ADH
secretion begins to increase. Below this set point, no ADH is released. The set
point among healthy adults varies between 280 and 290 mOsm/kg H2O.
A decrease in blood volume or arterial pressure also stimulates ADH
secretion. The receptors activated by this response are located in both the
low-pressure (left atrium and pulmonary vessels) and the high-pressure (aortic
arch and carotid sinus) sides of the circulatory system. Both groups of
receptors are sensitive to stretch of the wall of the structure in which they
are located. Signals from these receptors are carried by afferent fibers of the
vagus and glossopharyngeal nerves to the brainstem. Normally, signals from these
receptors tonically inhibit ADH secretion; however, when blood volume or
pressure decreases, this inhibitory input is overridden & ADH secretion is
stimulated.
The primary action of ADH on the kidney is to increase the permeability
of the collecting duct to water. ADH binds to V2 receptor on the
basolateral membrane of the cell. Binding of ADH to this receptor, which is
coupled to adenylyl cyclase via a stimulatory G protein increases the
intracellular levels of cAMP. The rise in intracellular cAMP activates protein
kinase A, which prompts the insertion of intracellular vesicles containing water
channels into the apical membrane of the cells. These water channels allow for
entry of water into the apical membrane cells from the tubular fluid. Water that
enters the cell exits across the basolateral membrane, resulting in net
absorption of water from the tubule lumen into peritubular blood. The increased
uptake of water from the tubular fluid helps to conserve water and returns body
fluid osmolality to normal.
When body fluid osmolality is increased or blood volume or pressure are
reduced, the individual perceives thirst. An increase of 2 to 3% in plasma
osmolality or 10 to 15% decrease in blood pressure induces thirst and the desire
to drink. The neural centers involved in regulating water intake (thirst center)
are located in the anterolateral region of the hypothalamus (subfonical organ
and organum vascusum of the lamina terminalis). Decreases in ECF volume also
stimulate thirst by a pathway independent of that mediating thirst in response
to increased plasma osmolality. It is mediated in part via the renin-angiotensin
system. Angiotensin II acts on the subfornical organ to stimulate the thirst
center.
The ADH and thirst systems work in concert to maintain water balance. An
increase in plasma osmolality invokes drinking and, via ADH action on the
kidneys, conservation of water. Conversely, when plasma osmolality is decreased,
thirst is suppressed and, in the absence of ADH, renal water excretion is
enhanced.