Unit 7 - Regulation of Plasma Osmolarity

Question 1

what is the body balance of water?

Answer 1

both gain and loss = 2500 mL

gain: ingested fluid 1200, ingested food 1000, metabolism 300
loss: urine 1500 (regulated); feces 100, skin/sweat 550, exhaled air 350 (unregulated)

Question 2

how is normal ECF osmolarity preserved?

Answer 2

kidney can maximize (concentrate) or minimize (dilute) urine osmolarity in response to increases/decreases in ECF osmolarity due to an excess/deficit of water consumption

Question 3

what is urine and ECF osmolarity when

1. (U/P)osm = 1?
2. (U/P)osm > 1?
3. (U/P)osm < 1?

Answer 3

1. urine is isotonic, and ECF is isotonic
2. both are hypertonic, but urine is more hypertonic
3. both are hypotonic, but urine is more hypotonic

Question 4

what is typical osmolar excretion and urine osmolarity?

Answer 4

osmolar secretion is usually 600 mOsm/day in urine, with volume of 1.5 L/day so typical Uosm = 600/1.5 = 400 mOsm/L

Question 5

what does the kidney do to Uosm if high water intake?

Answer 5

reduces from 400 to as low as 30 mOsm/L (10% of plasma osmolarity)
-so if typical daily osmolar excretion of 600 mOsm/day, max urine volume = 600/30 = 20 L/day

Question 6

what does the kidney do to Uosm if restricted water intake (or excessive loss)?

Answer 6

increases from 600 to as high as 1200 mOsm/L (400% plasma osmolarity)
-so if typical osmolar excretion of 600 mOsm/day, max urine volume = 600/1200 = 0.5 L/day

Question 7

what is “free water”?

Answer 7

retained or excreted water in excess (in spite of) solute (IOW, water is not osmotically obligated to stay anywhere b/c of solute)

Question 8

what is the ability of the kidney to defend against an increase in plasma osmolarity dependent upon?

Answer 8

making a concentrated urine with higher osmolarity than plasma
-kidney can increase osmolarity in urine up to 1200 mOsm/L (“free water” from tubular fluid is returned to plasma, diluting plasma osmolarity and increasing plasma volume)

Question 9

what is the ability of the kidney to defend against a decrease in plasma osmolarity dependent upon?

Answer 9

making a dilute urine with a lower osmolarity than plasma
-kidney can decrease osmolarity in urine to 30 mOsm/L (“free water” from plasma is added to tubular fluid, concentrating plasma osmolarity and decreasing plasma volume)

Question 10

what happens to free water clearance when:

1. (U/P)osm = 1?
2. (U/P)osm > 1?
3. (U/P)osm < 1?

Answer 10

keeping in mind that Cosm = (Uosm*V / Posm)

1. Cosm = V, so free water clearance = 0 (kidney neither adds nor removes free water from plasma)
2. Cosm > V, so free water clearance < 0 (negative free water clearance = urine is hyperosmotic b/c kidney retains water for plasma)
3. Cosm < V, so free water clearance > 0 (positive free water clearance = urine is hyposmotic b/c kidney eliminates water from plasma)

Question 11

what are positive and negative free water clearance limited by?

Answer 11

magnitude of solute consumed

Question 12

what will happen to negative and positive free water clearance when in solute balance with a diet low in solute (600 Osm/day)? high in solute (1200 mOsm/day)?

Answer 12

low solute diet
increase negative free water clearance, and decrease positive free water clearance

high solute diet
decrease negative free water clearance, and increase positive free water clearance
-increased solute excretion forces kidney to excrete more water to eliminate extra solute in urine

Question 13

are we better adapted to withstand excess of water or a deficit?

Answer 13

an excess of water

Question 14

how is urine diluted?

Answer 14

NaCl reabsorption in absence of water reabsorption

• in tubule segments with low water permeability (thin and thick ascending limb, distal tubule) dilute tubular fluid to 120 mOsm/L
• positive free water clearance (dilute, hyposmotic urine)

Question 15

how is urine concentrated?

Answer 15

NaCl reabsorption in thick ascending limb makes hypertonic interstitial surrounding collecting tubules in renal medulla

• osmotic equilibraion of tubular fluid in collecting duct with hypertonic interstitium causes water reabsorption, which concentrates tubular fluid to max 1200 mOsm/L
• negative free water clearance (concentrated, hyperosmotic urine)

Question 16

relative osmolarity of tubule fluid along nephron

Answer 16

proximal tubule: isosmotic
end of LoH: hyposmotic
end of CD (with ADH): hyperosmotic (antidiuresis/water restriction)
end of CD (w/o ADH): hyposmotic (water diuresis)

Question 17

how does ADH change water permeability?

Answer 17

increases water permeability of distal nephron from cortex (late distal tubule) to inner medulla (collecting duct)
-allows absorption of water in excess of solutes (free water)

Question 18

what is the circulating half-life of ADH, and what does this mean?

Answer 18

it’s short (18 minutes) meaning there is timeliness of process of detecting changes in plasma osmolarity and signaling kidney to respond appropriately
-once plasma hyperosmolarity is corrected, ADH secretion decreases, and there’s rapid enzymatic degradation of hormone to minimize an “over correction”

Question 19

how is water permeability increased?

Answer 19

1. vesicles containing aquaporin fuse with apical membrane facing tubular fluid
2. aquaporins allow transcellular flow of H2O driven by osmosis, from tubular lumen into cell and from cell into hypertonic medullary osmolarity
3. results in retention of “free water” and negative free water clearance (excreting urine with high osmolarity)

Question 20

what are ADH’s effects on vascular smooth muscle?

Answer 20

vasoconstriction to maintain blood pressure and flow when blood volume is severely reduced (hemorrhagic shock)

Question 21

by how much does ADH increase water permeability in collecting ducts?

Answer 21

increases cortical from 50 to 1000 um/sec, and inner medulla from 0 to 100 um/sec
-but even with ADH, is nowhere near PT and tDLH (>10,000 um/sec) without ADH

Question 22

aquaporin structure

Answer 22

tetramers of 4 identical monomers

-water molecule selective

Question 23

what happens if the posterior pituitary is removed, and/or a posterior pituitary extract is given after a bolus of water then NaCl is given?

Answer 23

PP intact: increased urine outflow after water, and decrease outflow after NaCl
-ADH will decrease outflow too

PP removed: urine flow will increase after water, but won’t decrease after NaCl is added
-exogenous ADH will still cause decreased outflow