Lecture 9: Water Balance, Urinary Concentration and Dilution

Question 1

What are the pathological causes of water loss?

Answer 1

1. vascular bleeding
   
   • loss of H2O andNa
2. Vomiting
   
   • loss of H2O and H+
3. Diarrhea
   
   • loss of H2O and HCO3-

Question 2

What is water steady state?

Answer 2

Amount ingest = amount eliminated

Question 3

What are types of water gain?

Answer 3

1. food and drink
2. metabolism
   (glucose + O2  CO2 + H2O)

Question 4

What are types of physiologic water loss?

Answer 4

1. skin
2. Lungs
3. Urine
4. Feces

Question 5

What is the normal response to water loading?

Answer 5

A rapid decrease in urine osmolality

Thick ascending limb = why there is low salt but high water content for urine for this phenomenon

Question 6

What is the normal response to water deprivation?

Answer 6

Upregulation of vasopressin and urine osmolality will shoot up

Question 7

What is the logic of renal water handling?

Answer 7

Since water availability is certain (at least in the Caveman days), the kidney must have the capacity to either conserve water effectively or to excrete water to maintain balance if water intake is excessive
System is designed to keep total body water (TBW) in a really narrow range

Question 8

What is the overall plan of renal regulation of water conservation/excretion?

Answer 8

1. Develop and maintain a high solute content with a gradient from inner cortex down to the tip of the inner medulla
2. Deliver lots of fluid through this gradient
3. Have a signaling system which senses water needs and delivers a hormonal switch to the tubules to either allow or prevent water passing from tubules into the renal interstitium to be returned to the circulation

Question 9

How does one establish a cortical to medullary osmotic gradient?

Answer 9

Theory 1:
Use of a structure with hairpin loop (ascending and descending limb)
The loop is initially filled with isosmotic solution containing solute at 300 mmole/kg
The ascending portion contains solute pumps which can pump solute from ascending limb to achieve a max gradient of 20 mosm/kg water at any transverse segment
The descending portion allows water to diffuse out in response to the osmotic gradient created by solute pumps
Won’t be asked to describe in detail because no model fully does it

Question 10

What are the characteristics of the Countercurrent Multiplier Model?

Answer 10

Step 1: tubule is initially filled with isotonic fluid
Step 2: Na is pumped out of ascending loop raising the osmotic pressure and lowering it inside
Step 3: Water flows out of the descending limb by osmosis, raising the osmotic pressure on the descending tubule to 400 mOsm/L
Step 4: Fresh fluid enters the glomerulus, pushing 400 mOsm/L into the ascending limb into ascending limb
E. The 2nd round of Na pump produces another 200 mOsm/L gradient across the membrane, but water does not go through because this is a SELECTIVE membrane that only lets across Na…so each round of successive Na pumping will lead to a more concentrated cortex/medulla

Question 11

Why do kidneys stop at 1200 concentration?

Answer 11

Because tubule isn’t long enough?

According to goldfarb’s notes: limited by diffusional processes because gradient eventually peters out

Question 12

How does concentration of cortex and medulla compare?

Answer 12

Medulla can be 4x the concentration of cortex

Question 13

What is the problem for the inner medulla where most of the gradient occurs?

Answer 13

The descending and ascending LoH have little transport activity
The two contrast between the two types of nephrons, cortical vs juxtamedullary nephron, exposes this fallacy
Cortical nephron makes sense because thick ascending limb can secrete the Na which is the model that was noted before
However, juxtamedullary nephron does NOT have a thick ascending limb that spans the medulla (only a small portion of the outer medulla)
-only has thin limbs (which has no active transport)
-therein lies the weakness of the countercurrent model

Question 14

How does one explain the inner medulla capacity to create an
osmotic gradient?

Answer 14

The passive permeability model

Question 15

What is the passive permeability model?

Answer 15

1. urea is transported actively into the interstitium at the BOTTOM of the collecting duct
   -this raises osmolality of inner medulla
2. Solute concentration of tubule starts to rise as water is removed since descending LoH is water and not salt soluble
3. This leads to a rising sodium concentration in last parts of descending limb
4. more sodium in descending limb means more Na to secrete in the ascending limb, thin and thick…thick just augments with NCCK2 pump
   Issues with this model as well

Question 16

What do studies show about the
Relationship between collecting ducts and
Descending LoH?

Answer 16

Descending LoH is farther away from collecting
Ducts so as not to disturb gradient
Not going to be tested on the experiments

Question 17

How does the kidney make sure the blood does not wash out the gradient established by counter-current exchange multiplier?

Answer 17

How does the kidney make sure the blood does not wash out the gradient established by counter-current exchange multiplier?

Question 18

How is the permeability of the collecting duct modified to serve the need for excreting or reabsorbing water from the dilute fluid presented to the duct?

Answer 18

ADH will retain water

Hormonally regulated at level of collecting duct

Question 19

What triggers increase in vasopressin synthesis in posterior hypothalamus?

Answer 19

1. osmolarity greater than 280 mOsm
   
   • by hypothalamic osmoreceptors
   • as osmolality rises, hypothalamic osmoreceptors undergo a reduction in cell volume to upregulate vasopressin release
2. Decreased atrial stretch due to low blood volume
   
   • atrial stretch receptor
3. Decreased blood pressure
   
   • carotid and aortic baroreceptors

Question 20

Does ADH get released during heart failure?

Answer 20

Yes because osmolarity decreases even though body is hypovolemic

Question 21

What is the MoA of vasopressin?

Answer 21

Vasopressin is produced by posterior pituitary
Travels through blood
Binds to V2 vasopressin receptor on basolateral membrane in collecting duct cell
Vasopressin + V2 receptor (G-protein coupled receptor) = increased cAMP = increased PKA
Increased cAMP and PKA will upregulate expression of aquaporin2 water pores
Aquaporin-2 water pores leads to greater uptake of water

Question 22

What is the relationship between plasma vasopressin and urine osmolality?

Answer 22

Directly proportional

Question 23

How does one assess the status of urinary concentration?

Answer 23

1. Since the system is responsive to the state of body fluids, urinary concentrating function (or diluting function) can only be measured under defined conditions
2. To determine max concentrating function, urine must be collected after 12 hrs of fasting or when patient has elevated plasma osmolality
   Normal 800 mOsm/kg (max is 1200 mOsm/Kg but requires several days of low fluid intake to maximally concentrate inner medulla)

Question 24

If urine with 140 mOsm/Kg were secreted, how can one tease that out into two volumes?

Answer 24

1. 500 ml urine with 280 mOsm
   +
2. 500 ml of urine with 0 mOsm
   It is 1 L of volume because it is equal to 1kg of urine

Question 25

What is free water clearance?

Answer 25

The volume of the water cleared per given unit of time

Question 26

Thus what can a sample of urine be thought as?

Answer 26

Two moieties

1. The volume that would be necessary to dissolve all excreted solutes at a concentration that is isomotic with blood plasma
2. The volume of pure or solute-free-water-or simply free water that one must add/subtract to previous volume to account for entire urine volume