OBJECTIVE 3: TO UNDERSTAND THE PROCESS BY WHICH AN
OSMOTICALLY DILUTE URINE IS FORMED.
A. When water intake is excessive and ADH secretion is suppressed, the kidney is able to excrete copious amounts of water without a large increase in solute excretion. This permits the organism to maintain the osmotic concentration of the extracellular fluid constant.
B. The kidney dilutes the urine and increases water excretion by reabsorption of solute in the distal segments of the nephron when the absence of ADH has reduced water reabsorption. Osmotic dilution of the urine begins in the thick ascending limb and continues in the initial segment of the distal tubule whether ADH is present or not. In these segments the fractional reabsorption of solute always exceeds fractional water reabsorption and together they are called the "diluting segment". It is in these segments that the osmotic concentration of the tubular fluid falls below that of the glomerular filtrate. In the succeeding segments of the nephron, fractional solute reabsorption continues to exceed fractional water reabsorption when ADH is absent. In the human, water excretion can reach as high as 20 L/day or 11% of the GFR. The osmotic concentration of the urine can be as low as 40-60 mosmole/kg H2O. This is called water diuresis.
C. To understand the sequence of events in the body=s response to an intake of water, consider a subject weighing 70 kg who ingests one liter of water. As the water is absorbed into the blood from the gastrointestinal tract, it passes by osmosis into both the extracellular and intracellular water compartments, reducing the osmotic concentration of both compartments to the same level. Cells contain 72% of total body water. Thus, cells also contain 72% of the osmotically active solute. Therefore, in diluting both compartments to the same concentration, 720 ml of the ingested water will enter the intracellular compartment and 280 ml will remain in the ECF. This is a small increase in the volume of the ECF (2.5%) and only a small fraction of that remains in plasma.
1. The change in blood volume is probably not large enough to trigger any of the reflex mechanisms controlling the volume of the ECF; nor is it large enough to alter significantly the blood pressure or the colloid osmotic pressure of the plasma. Thus, there is little change in GFR.
2. There is, however, a small but distinct drop in the osmotic concentration of the body water of about 7 mosmole/kg H2O or 2.5%. This small change is enough to affect the very sensitive osmoreceptors, causing them to inhibit ADH release from the posterior pituitary.
3. Within 15 to 20 minutes, this drop in secretion, together with the continued metabolism and excretion of circulating ADH, causes a fall in the plasma concentration of ADH. The collecting tubules then begin to lose their permeability to water and the urine flow begins to rise and reaches a peak of about 15 ml/min in 60 to 90 min.
4. As water is excreted, the osmotic concentration of the ECF begins to rise, water begins to leave the body cells, including the osmoreceptors, and ADH secretion begins to rise. In 120 to 150 min, the urine flow returns to the control level. By that time almost all the ingested fluid has been excreted. During this period, there has been no change in GFR and little change in solute excretion. The major change has been in water excretion and the major reason for that change has been the fall in the plasma concentration of ADH.
D. The syndrome of diabetes insipidus is a disorder of the ADH system. It is characterized by the excretion of large quantities of dilute urine. This may be due to a primary insufficiency of ADH, related to dysfunction or loss of function of the hypothalamic-neurohypophyseal tract; an inability of the kidney to respond to ADH (nephrogenic diabetes insipidus); or a psychogenic disorder causing compulsive water drinking (polydipsia), which physiologically reduces the secretion of ADH. The first type can be successfully treated with synthetic analogs of ADH, which have greater antidiuretic potency and much less vasopressor activity than ADH. One of these is desmopressin.
QUESTIONS:
4. At what point in the
nephron does the dilution process begin? How does it occur? What is
required so that the process continues in the later segments of the distal
tubule and in the collecting tubule?
5. The following data were obtained in an
experiment on a normal male subject weighing 77 kg who had taken in no
fluids during the preceding 10 hours.
Time
Posm
Pcr
V
Uosm
Ucr
UosmV
min
mOsmole/kg
mg/dl
ml/min
mOsmole/kg
mg/dl
mosmoles/min
0
Empty bladder and begin 1st
clearance period.
60
End 1st clearance period and collect
blood sample.
290
1.2
0.54
1034
289
62-69
Subject drinks 1200 ml water.
130
Empty bladder and begin 2nd
clearance period
160
End 2nd clearance period and collect
blood samples
283
1.15
11.0
82
13.8
220
Empty bladder and begin 3rd clearance
period.
250
End 3rd clearance period and collect
blood sample
288
1.2
1.1
490
143
a. Calculate the rate of excretion of osmoles for each period.
b. What osmotic concentration and volume changes were produced in each of the three body water compartments by the intake of water?
c. List the sequence of events beginning with the water intake that led to an increase in V and the decrease in Uosm.
d. Compare the changes in the rates of excretion of water and of solute. Is this significant? Why?
e. What processes reduced the urine osmotic concentration below that of plasma?
f. Would aldosterone secretion have been affected? Would reabsorption in the proximal tubule have been altered? Did GFR change? Why?
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