Physiology of the Kidneys 597reabsorbed. A decrease in ADH, conversely, results in less reab-
sorption of water and thus in the excretion of a larger volume
of more dilute urine ( fig. 17.20 ). ADH is produced by neurons
in the hypothalamus and is released from the posterior pituitary
(chapter 11; see fig. 11.13). The secretion of ADH is stimu-
lated when osmoreceptors in the hypothalamus respond to an
increase in blood osmolality above the normal range (gener-
ally 280–295 mOsm). During dehydration, therefore, when the
plasma becomes more concentrated, increased secretion of ADH
promotes increased permeability of the collecting ducts to water.
In severe dehydration only the minimal amount of water needed
to eliminate the body’s wastes is excreted. This minimum, an
obligatory water loss of about 400 ml per day, is limited by the
fact that urine cannot become more concentrated than the med-
ullary interstitial fluid surrounding the collecting ducts. Under
these conditions about 99.8% of the initial glomerular ultrafil-
trate is reabsorbed.membranes to travel from the Golgi apparatus and fuse with
the plasma membrane. This is similar to exocytosis, but instead
of the secretion of cellular products, the process adds aqua-
porin channels to the plasma membrane in response to ADH
stimulation.
In response to ADH, therefore, the collecting duct
becomes more permeable to water. When ADH is no longer
available to bind to its membrane receptors, the water chan-
nels are removed from the plasma membrane by a process of
endocytosis ( fig. 17.19 ). Endocytosis is the opposite of exo-
cytosis; the plasma membrane invaginates to reform vesicles
that again contain the water channels. Alternating exocytosis
and endocytosis in response to the presence and absence of
ADH, respectively, results in the recycling of water channels
within the cell.
When the concentration of ADH is increased, the collect-
ing ducts become more permeable to water and more water is
Figure 17.19 ADH stimulation of aquaporin
channels. ( a ) When ADH is absent, aquaporin channels are
located in the membrane of intracellular vesicles within collecting
duct epithelial cells. ( b ) ADH stimulates the fusion of these
vesicles with the plasma membrane and ( c ) the insertion of
the aquaporin channels into the plasma membrane. ( d ) When
ADH is withdrawn, the plasma membrane pinches inward (in
endocytosis) to again form an intracellular vesicle and to remove
the aquaporin channels from the plasma membrane.
Fusion of exocytotic vesiclePlasma membrane with
aquaporin channelsFormation of
endocytotic vesicle(b)(d) (c)Vesicle(a)CytoplasmExtracellular
fluidAquaporin
channelsADHADHNo
ADHNo
ADHFigure 17.20 Homeostasis of plasma concentration
is maintained by ADH. In dehydration ( left side of figure ), a rise
in ADH secretion results in a reduction in the excretion of water in
the urine. In overhydration ( right side of figure ), the excess water is
eliminated through a decrease in ADH secretion. These changes
provide negative feedback corrections, maintaining homeostasis of
plasma osmolality and, indirectly, blood volume.Low water intake
(dehydration)Plasma
osmolalityADHStimulusSensor
Integrating center
EffectorWater
reabsorptionWater
reabsorptionADHPlasma
osmolalityHigh water intake
(over-hydration)Less water
excreted in urineMore water
excreted in urineOsmoreceptors in
hypothalamusKidneysNegative
feedback
correctionNegative
feedback
correctionStimulusPosterior pituitary