Concentration and Dilution of Urine

Question 1

Countercurrent multiplier

Answer 1

Sets up osmotic gradient in loop of Henle

Deposits NaCl into bottom of loop of Henle by ascending limb dumping osmoles into interstitum, then flow from PCT into descending limb bringing those osmoles down to the bottom

Osmolality transferred from ascending limb to descending limb

Question 2

Single effect step of countercurrent multiplier

Answer 2

Produces 200mOsm gradient between ascending and descending limb

Thick ascending limb of loop of Henle is impermeable to water but Na/2Cl/K pumps ions into interstitial space and out of fluid –> increased osmolarity of interstitial fluid (400mOsm/L0 near thick ascending limb, and dilute fluid (200mOsm/L) in thick ascending limb

Descending limb of loop of Henle is permeable to water, so water exits and goes into interstitial fluid to equalize –> increased osmolarity of descending limb and still of interstitial fluid too (400mOsm/L)

Note: ADH stimulates Na/2Cl/K pump

Question 3

Flow of tubular fluid in countercurrent multiplier

Answer 3

Fluid entering descending limb of loop of Henle from PCT is 300 mOsm/L, and pushes 400mOsm/L fluid down

Then, single effect happens again so in ascending limb the osmolarity in tubule decreased and osmolarity in interstitial fluid increased. Descending limb will equalize to interstitial fluid high concentration set up by ascending limb.

Question 4

What can affect the degree to which the urine is concentrated?

Answer 4

1) ADH (increases activity of Na/2Cl/K cotransporter, needed for urea recycling, and inserts water channels for reabsorption)
2) Length of the loop of Henle
3) Rate of solute transport out of ascending limb
4) Permeability of descending limb
5) Flow rate of tubular fluid

Question 5

Urea recycling and contribution to countercurrent multiplier effect

Answer 5

After PCT (where 50% of urea reabsorbed), nothing else is permeable to urea until INNER (bottom) medullary collecting tubule, so high concentration of urea in tubular fluid by the time it gets to bottom of collecting tubule

ADH increases water and urea permeability (by increasing transporter for facilitated diffusion of urea, UT1) in inner medullary collecting tubule, so urea diffuses down conc gradient into interstitial space (this equalizing enough to increase interstitial osmolality a lot)

Adds solute to bottom interstitial space so contributes to concentration gradient and increases countercurrent multiplier effect

Note: need ADH for urea recycling

Question 6

ADH effects on countercurrent multiplier effect

Answer 6

1) ADH stimulates Na/2Cl/K pumps in thick ascending limb in single effect step of countercurrent multiplier
2) ADH inserts UT1 (urea transporters) into medullary (bottom) part of collecting ductso urea goes into interstitum and increases effect of countercurrent multiplier

Note: if no ADH (central diabetes insipidus or drank a lot of water), then no urea recycling because it depends on ADH

Question 7

Vasa recta

Answer 7

Blood flow through vasa recta is low

Have countercurrent EXCHANGE

Since capillary walls of vasa recta are very permeable to salt, blood follows same gradient as countercurrent multiplier set up

Note: blood leaving vasa recta at top is a little more concentrated than what entered but gradient is not dissipated because countercurrent multiplier mechanisms continuously replacing solute carried away

Question 8

ADH

Answer 8

1) Increases water permeability of principal cells in late distal tubule and collecting duct
2) Increases actibity of Na/2Cl/K pump to increase countercurrent multiplication
3) Increases urea permeability in inner medullary collecting duct, enhancing urea recycling and countercurrent multiplication

Question 9

Mechanism of ADH

Answer 9

ADH in bloodstream binds V2 receptors on basolateral membrane –> G-coupled ptotein response activates adenylyl cyclase –> cAMP produced –> cAMP activates PKA –> PKA phosphorylates targets (uncertain) –> vesicles with AQP2 channels inserted into luminal membrane of principal cell –> reabsorption of water

Question 10

Creating hyperosmotic urine (greater osmolality than blood)

Answer 10

Osmolality in blood and thus in filtrate is 300mOsm/L

Thick ascending limb reabsorbs salt via Na/2Cl/K pump but is impermeable to water so dilutes tubular fluid (100mOsm/L)

Early distal tubule dilutes fluid even more (80 mOsm/L)

Late distal tubule/collecting duct respond to ADH which let water flow out, and urine gets constantly concentrated to equalize with gradient from countercurrent multiplier (gets to 1200 mOsm/L by the end)

Want hyperosmotic urine when low volume state, trying to hold onto fluids

Question 11

Creating hypoosmotic urine (lower osmolality than blood)

Answer 11

Osmolality in blood and thus in filtrate is 300mOsm/L

Thick ascending limb reabsorbs salt via Na/2Cl/K pump (but not as much in absence of ADH) but is impermeable to water so dilutes tubular fluid (120mOsm/L)

Early distal tubule dilutes fluid even more (110 mOsm/L)

Late distal tubule/collecting duct are impermeable to water because no ADH, so even as fluid goes down gradient, it doesn’t equalize and NaCl is even reabsorbed here too which dilutes urine even more (75 mOsm/L at end)

Want hyposmotic urine when high volume state, trying to get rid of fluid

Question 12

Water input routes

Answer 12

Food and drink

60-97% of weight in food is water

Metabolic water is usually <10%; but metabolism of carbohydrates, fats and proteins creates water too

Question 13

Water output routes

Answer 13

Insensible: losses you’re not aware of; skin (water vapor), lungs (breathing)

Sensible: losses you are aware of; sweat (hypotonic), feces (isotonic), urine output is regulated to meet body needs

Question 14

How does the body measure osmolality?

Answer 14

Osmoreceptors in hypothalamus outside the blood brain barrier swell or shrink when osmolality changes –> membrane stretch alters pattern of nerve impulse generation –> signals to large bodied cells of paraventricular and supraoptic nuclei which synthesize ADH –> neuron axons travel down to posterior pituitary and release granules of ADH

When osmolality differs from 285 mOsm/L, ADH release changes

Question 15

When does ADH secretion start and when does thirst start?

Answer 15

ADH secreted right away when it senses plasma osmolality higher than 285 mOsm/L, and continues to be secreted even after thirst kicks in

Thirst only beings when plasma osmolality is higher than 290 mOsm/L

Question 16

How does the body adjust thirst induced water intake?

Answer 16

Osmoreceptors controlling thirst are near (but different from) osmoreceptors that trigger ADH release

You need drinking behavior in order to maintain water balance. Drinking behavior can even hide renal problems if you are able to drink enough to maintain water balance

Question 17

Does the body sense changes in osmolality or volume better?

Answer 17

At normal circulating volume, body senses changes in osmolality better–ADH is released right away

However, when huge volume depletion (hemorrhage), the baroreceptors respond to decreased stretch and cause ADH secretion and thirst. Also, angiotesin II acts on the brain to increase release of ADH during decreased volume state.

Question 18

Normal urine osmolality

Answer 18

Can range from 50-1400 mOsm

When osmolality of body fluids >295, kidneys concentrate urine to retain fluid

When osmolality of body fluids <275, kidneys dilute urine to get rid of fluid

Healthy kidneys get rid of water 10x more rapidly than they can conserve water

Question 19

What happens when you have osmotic diuresis (when you have too much solute in your filtrate)?

Answer 19

That solute (mannitol in experiments, glucose in diabetes mellitus) in the PCT causes less water to be reabsorbed there –> get higher flow through the nephron –> inability to concentrate urine because of mechanisms below:

1) High medullary blood flow washes out osmotic gradient created by countercurrent multiplication
2) High medullary flow rate (super fast) reduces ability to equilibrate in collecting tubule even in the presence of ADH so you can’t reabsorb as much water

Question 20

What happens to salt when you get extreme (<80-90%) hypovolemia?

Answer 20

You actually get hyponatremia because you just try to conserve WATER first, don’t care as much about restoring osmolality/salt balance