Water Balance

Question 1

Which of the following nephron segments has the lowest water permeability under any circumstance?

a. Proximal tubule
b. Descending limb of the loop of Henle
c. Ascending limb of the loop of Henle
d. Cortical collecting duct
e. Inner medullary collecting duct

Answer 1

b - ascending loop of henle

Question 2

In the genetic form of nephrogenic diabetes insipidus, loss-of-function mutations in the vasopressin V2 receptor impair the response of the collecting duct to antidiuretic hormone (ADH). What is the likely consequence of this impairment at the cellular level?

a. Aquaporin-1 water channels are not inserted into the plasma membrane
b. The V2 receptor causes excessive activation of adenylyl cyclase
c. Water permeability of collecting duct membranes remains low even in the presence of high circulating levels of ADH
d. Aquaporin-2 water channels are mis-localized to the basolateral membranes

Answer 2

c - water permeability is low even with a lot of ADH

Question 3

A 23 year female suffers a head injury in a motorcycle accident. Several days later, she notes polyuria and intense thirst. Her urine appears extremely clear (“like water”) and she has to drink more than 5 liters of water per day to satisfy her thirst. Medical evaluation revealed a urine osmolality of 90 msom/l and a serum vasopressin level of < 1 pg/ml (undetectable). A diagnosis of acquired central diabetes insipidus was made. Interestingly, despite the near absence of vasopressin and excretion of large volumes of dilute urine, her serum sodium concentration was only mildly elevated (147 mEq/L; normal range 135-145 mEq/L) as was her serum osmolality (296 mosm/l; normal range 280-290 mosm/l). Why doesn’t she have a more severe degree of hypernatremia and hyperosmolality?

a. although vasopressin levels are low, females have circulating oxytocin that can promote water reabsorption.
b. She has maintained a low dietary sodium intake.
c. Her thirst mechanisms are intact and she has been drinking water.
d. She has normal sodium balance and this is maintaining her serum sodium concentration near the normal range.
e. The laboratory tests must be wrong.

Answer 3

c. Her thirst mechanisms are intact and she has been drinking water.

a. although vasopressin levels are low, females have circulating oxytocin that can promote water reabsorption.
No evidence for this
b. She has maintained a low dietary sodium intake.
Hypernatremia does not tell you anything about total body Na
d. She has normal sodium balance and this is maintaining her serum sodium concentration near the normal range.
Na concentration reflects water balance not sodium balance
e. The laboratory tests must be wrong.
Always possible, but there are more rationale explanations

Question 4

Potassium secretion by the collecting duct is affected by all of the following factors EXCEPT:

a. lumen-negative transepithelial voltage in the collecting duct
b. aldosterone stimulated sodium reabsorption by principal cells in the cortical collecting duct
c. tubular fluid flow rate in the collecting duct
d. concentration of bicarbonate in collecting duct tubular fluid
e. vasopressin stimulated water reabsorption in collecting duct

Answer 4

e. vasopressin stimulated water reabsorption in collecting duct
Water reabsorption is irrelevant to K secretion

Question 5

Define osmoregulation

Answer 5

The physiological control of extracellular fluid osmolality is called osmoregulation.

Question 6

What is Na concentration a proxy for?

Answer 6

the main clinical index of the state of ECF osmolality is the serum Na+ concentration and it is dangerous to confuse this measurement as an index of ECF volume (there is no routinely employed direct measurement of ECF volume - this must be assessed clinically using the physical examination).

Question 7

What drives water reabsorption in the collecting duct?

Answer 7

hypertonic medullary interstitium created by counter current multiplier

Question 8

What is required to excrete dilute urine?

Answer 8

for the kidneys to excrete dilute urine, ADH levels in plasma must be suppressed and the activity of the thick ascending limb of the loop of Henle must be intact (to achieve maximal separation of salt and water).

Question 9

• Stimulation of ADH release
• hypertonic medullary interstitium
• functional V2 receptors in CCD
• functional AQP2 in CCD
  These are requirements for what kind of urine: concentrated or dilute?

Answer 9

concentrated

Question 10

• suppressed ADH release
• adequate NaCl delivery to TAL
• separation of salt and water by TAL
  These are requirements for what kind of urine: concentrated or dilute?

Answer 10

dilute

Question 11

What is the equation that allows us to estimate free water clearance?

Answer 11

C H2o = V - C osm

where V : urine flow rate, and Cosm: osmolal clearance

Question 12

IF CH2o is positive, what is the concentration of the urine?

Answer 12

dilute - solute free water is excreted

Question 13

if CH2O is negative, what is the concentration of the urine?

Answer 13

concentrated - solute free water is retained

Question 14

What is true of the osmolality of tubular fluid in the CCD compared to the interstitiuM?

Answer 14

lower osmolality, driving force for water reabsorption when there are aquaporins

Question 15

What is the final determinant of urine osmolality?

Answer 15

water reabsorption in the medullary CD

Question 16

What are osmotic diuretics?

Answer 16

Osmotic diuretics such as mannitol do not directly affect transporters or pumps along the nephron. This class of diuretics acts by blunting the driving force for water reabsorption from water permeable nephron segments. Mannitol is freely filtered at the glomerulus but is not reabsorbed or metabolized along the nephron. It raises intraluminal osmolality and blunts the osmotic gradient between tubular lumen and surrounding interstitium. This will impair osmosis from water permeable nephron segments, and result in greater urine volume.

Question 17

How does hyperglycemia cause diuresis?

Answer 17

glucose is an osmotic diuretic that raises the osmolality of the tubular fluid relative to the interstitium, blunting the driving force for water reabsorption

Question 18

Which transporters are responsible for urea recycling?

Answer 18

uT-A2 in the descending limb of the loop of Henle

UT-A1 and A3 in the IMCD

UT-B in descending limb of vasa recta

Question 19

What is caused by a deficiency of Ut-B transporters in RBC?

Answer 19

Rare individuals who genetically lack the Kidd antigen (i.e. deficiency of UT-B) are unable to concentrate their urine to greater than 800 mOsm/kg after overnight water deprivation and infusion of vasopressin. This has suggested that urea transport in vasa recta is crucial to maximal urinary concentrating ability.

Question 20

Which aquaporin is constitutively active? where it is located?

Answer 20

AQP 1, PT and DTL

Question 21

Where is ADH synthesized?

Answer 21

supraoptic and paraventricular nuclei of hypothalamus

secreted through posterior lobe of the pituitary gland

Question 22

HOw does ADH cause increased insertion of water channels?

Answer 22

ADH interacts with the V2 vasopressin receptor on basolateral membranes of collecting duct cells. Binding to this receptor triggers an intracellular signaling cascade through G-protein mediated activation of adenylyl cyclase resulting in an increase in cyclic AMP (cAMP) levels. This signaling cascade ultimately stimulates the insertion of water channels into the apical membrane of collecting duct cells giving them substantially increased water permeability

Question 23

What is the one example that is an exception to the rule of hyponatremia = excess water?

Answer 23

The exception to the latter statement occurs in the case of extreme hyperglycemia (elevated blood glucose concentration) where the presence of abnormally high levels of a non-sodium solute (ie. glucose) “pulls” water from the intracellular compartment and dilutes extracellular fluid (causing serum [Na+] to be depressed).

Question 24

Define internal K balance

Answer 24

Internal K+ balance refers to the physiological control over the distribution of K+ between the intracellular and extracellular spaces (e.g., distribution across cell membranes).

Question 25

Define external K balance

Answer 25

External K+ balance refers to the net difference between dietary K+ intake and renal K+ excretion.

Question 26

• Na+/K+-ATPase activity
• Hyperosmolality of extracellular fluid
• Insulin
• pH of extracellular fluid
• Catecholamines (β2 adrenergic receptor)
• Cell breakdown
• exercise
• Na+/K+-ATPase inhibition

Which of these are physiologic regulators of internal K balance?

Answer 26

• Na/K atpase activity
• insulin
• catecholamines (beta 2)
• exercise

Question 27

• Na+/K+-ATPase activity
• Hyperosmolality of extracellular fluid
• Insulin
• pH of extracellular fluid
• Catecholamines (β2 adrenergic receptor)
• Cell breakdown
• exercise
• Na+/K+-ATPase inhibition

Which of these are Pathologic regulators of internal K balance?

Answer 27

• hyperosmolality of ECF
• pH of ECF
• cell breakdown
• Na/K ATPase inhibition

Question 28

How is Na/K ATPase activity increased by hormones?

Answer 28

insulin and catecholamines through Beta 2 receptors

Question 29

How does exercise increase external K?

Answer 29

Exercise causes an increase in muscle K+ release secondary to the opening of potassium channels in repolarizing muscle. Some of these potassium channels are inhibited by ATP and therefore vigorous exercise with depletion of cellular ATP stores will enable these ATP-sensitive channels to remain open longer thus permitting efflux of K+.

Question 30

What kinds of cell lysis are common causes of increased serum K?

Answer 30

For example, during rapid lysis of red blood cells (hemolysis), sudden release of K+ into the blood can raise K+ levels to levels sufficient to cause heart rhythm disturbances and possibly cardiac arrest. Wide spread lysis of tumor cells during chemotherapy (tumor lysis syndrome) or destruction of muscle (rhabdomyolysis) result from trauma or non- traumatic injury can have similar consequences.