2. Regulation of Body Fluid Osmolality – Regulation of Water Balance

Question 1

Is plasma ADH high or low in patients with central diabetes insipidus?

Answer 1

ADH is low – the posterior pituitary cannot produce it.

Question 2

How does aldosterone increase sodium retention and potassium excretion?

Answer 2

It increases the presentation of ENaC channels in the collecting duct. This increases the reabsorption of sodium, and causes a concomitant ejection of potassium.

Question 3

What is a medullary washout?

Answer 3

The event in which increased blood flow through the vasa recta dissipates the medullary gradient by literally washing out the solute.

Question 4

What would diabetes insipidus do to plasma sodium levels?

Answer 4

Diabetes insipidus increases plasma sodium levels

(Diabetes insipidus = hypernatremia)

Question 5

What two general mechanisms can be the cause of symptoms in nephrogenic diabetes insipidus?

Answer 5

Either a direct failure of the distal and collecting tubules to response to ADH,

or a failure of the countercurrent multiplier to establish a hyperosmotic medullary interstitium.

Question 6

What is the osmolality of the tubular fluid entering the descending limb of the loop of Henle?

Answer 6

Isotonic

Question 7

What four things (discussed along with polyuria) can increase the output of solutes in the collecting duct?

Answer 7

Diuretics, diabetes mellitus, hyperthyroidism, and hyperparathyroidism.

Question 8

What is normal urine output?

Answer 8

1 to 2 L/day

Question 9

What are the general functions of the intercalated cells?

Answer 9

Reabsorption of potassium.

Secretion of hydrogen.

Question 10

What is obligatory urine volume?

How do we calculate it?

Answer 10

Obligatory urine volume is the minimum amount of urine that would have to be produced to secrete the minimal amount of solutes that must be excreted.

Take the minimum amount of solute (about 600 mOsm per day) and divide by 1200 mOsm per liter, the maximum concentration of urine.

(.5 L/day for a normal 70 kg human)

Question 11

Interstitial fluid in the medulla is always at osmotic equilibrium with what portion of the nephron?

Answer 11

The descending limb of the loop of Henle.

(The medullary interstitial fluid and the descending loop of Henle will always have the same osmolality as they descend further into the medulla.)

Question 12

What will the osmolality of the intratubular fluid of the distal tubule be in the presence of ADH?

Answer 12

Maximum of 300 mOsm / kg H20

(recall that the interstitial fluid of the cortex is isotonic)

Question 13

In a patient with hypernatremia due to diabetes insipidus, what would we expect the osmolality of their urine to be?

Answer 13

Diluted (<300/<100)

Even though hypernatremia should increase the ability of the body to reabsorb water from the collecting ducts, the inability of the collecting ducts to respond to ADH makes this irrelevant.

Question 14

What urea transporters are responsible for urea exit from the inner medullary collecting duct?

Answer 14

UT-A1 / UT-A3

Question 15

What ADH related disease is a major cause of low sodium levels?

Answer 15

SIADH

Question 16

Where does almost all of the urea leave the nephron?

Answer 16

The inner medullary collecting duct.

Question 17

What portion of the collecting duct is always impermeable to water?

Answer 17

The cortical portion is always impermeable to water.

Question 18

What is considered oliguria?

Answer 18

300 to 500 mL/day

Question 19

When osmoreceptors are triggered, which pathway is triggered first: the ADH pathway, or the thirst pathway?

Answer 19

The ADH pathway is generally triggered first.

Question 20

What are the general functions of the principal cells?

Answer 20

Reabsorption of sodium, chloride, and water.

Secretion of potassium

Question 21

What urea transporter is responsible for urea uptake into the thin descending loop of Henle?

Answer 21

UT-A2

Question 22

What is the function of desmopressin?

Answer 22

Desmopressin directly acts on V2 receptors to increase reabsorption of water in the distal tubular segments.

Question 23

What is the maximum osmolality of the interstitium of the medulla of the kidney?

Answer 23

1200 to 1400 mOsm / kg H2O

Question 24

What are the four mechanisms that can cause polyuria?

Answer 24

Increase water intake.

Increased GFR.

Increased solute excretion.

Inability of the kidney to reabsorb water in the distal convoluted tubule.

Question 25

What can be determined by a U(osm)/P(osm) of greater than one, and less than one?

Answer 25

U(osm)/P(osm) of greater than one: kidneys are able to produce concentrated urine.

U(osm)/P(osm) of less than one: kidneys are able to produce dilute urine.

Question 26

When there is excess water in the body, what happens to the reabsorption of urea into the medullary interstitium?

Answer 26

Urea reabsorption into the medullary interstitium is reduced.

(There is a reduced concentration of urea and the inner medullary collecting ducts, therefore there is less urea to reabsorb)

Question 27

How is potassium secreted by the principal cells?

Answer 27

Potassium is up taken by the cell by the action of the Na/K ATPase, and then transported out of the cell down its concentration gradient.

Question 28

How can we clinically diagnose between central and nephrogenic diabetes insipidus?

Answer 28

Administer desmopressin. If urinary output quickly returns to normal, the patient has central diabetes insipidus. If it does not, nephrogenic diabetes insipidus is more likely.

Question 29

What would happen in the event of decreased blood flow through the vasa recta?

Answer 29

The net effect is that salt and solute transport out of the tubules of the nephron is decreased because there is less oxygen to the solute transporters of the nephron.

This results in the diminished ability to concentrate urine.

Question 30

What is considered anuria?

Answer 30

<50 mL/day

Question 31

What range is considered polyuria?

Answer 31

>2.5 L/day

OR

>40 mL/kg/day

Question 32

At any point along the length of the thick ascending loop of Henle, what is the difference between the osmolality of the tubular fluid, and the fluid of the interstitium?

Answer 32

200 mOsm / kg H2O

Question 33

What is considered polydipsia?

Answer 33

Water intake >100 mL/kg/day (6 L/day)

Question 34

What chemical mechanism directly causes release of ADH from the supraoptic and paraventricular nuclei?

Answer 34

Nerve stimuli causes an increase in membrane permeability to calcium – and concomitant increase in intracellular calcium. This causes ADH release.

Question 35

What three things (discussed along with polyuria) can increase GFR?

Answer 35

Fever, hyperthyroidism, hyper metabolic states

Question 36

What is the equation for free water clearance?

Answer 36

Free water clearance = urine flow rate - osmolar clearance

Osmolar clearance is calculated the same way we would calculate any other type of clearance. C(osm) = [U (osm) x V]/P (osm)

Question 37

What medications can cause nephrogenic diabetes insipidus?

Answer 37

Diuretics, lithium (antipsychotic), and tetracyclines.

Question 38

What is the function of the vasa recta?

(Three things)

Answer 38

Remove the water and the solute that is constantly added to the medullary interstitium.

Supply oxygen to the cells of the nephron.

Maintain the medullary interstitial gradient.

Question 39

The tubular fluid of the collecting ducts – is it hypotonic or hypertonic when under the effect of ADH?

What about in the absence of ADH?

Answer 39

ADH causes water resorption, and so the inter-tubular fluid is hypertonic

In the absence of ADH, the intertubular fluid is around 100 mOsm / kg H2O (hypotonic)

Question 40

How does the ascending loop of Henle maintain a 200 milliosmolar gradient between itself and the interstitial fluid?

Answer 40

Active sodium chloride channels, such as the Na+/K+/2Cl- transporter.