1. RENAL PHYSIOLOGY Origin of the Hyperosmotic Renal Medulla
continuing from last time
PHYSIOLOGY 451
RENAL PHYSIOLOGY
Dr. Michael Fill, Lecturer

2. Origin of the Hyperosmotic Renal Medulla
Page 62 in the Renal syllabus
Cortex
Medulla
mOsM
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Medulla is hyperosmotic
but there is also an
osmolarity gradient.

3. Origin of the Hyperosmotic Renal Medulla
Cortex
Medulla
mOsM
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Countercurrent
Multiplication
H20
reabsorbed Na
H20
Na+
reabsorbed
The 3 Essential Elements:
1) Active Na+ transport in thick ascending limb of loop.
( Overall, the loop always reabsorbs more Na+ than H20 )

4. Origin of the Hyperosmotic Renal Medulla
Vasa Recta
Blood Osmolarity
IN = OUT
mOsM
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Hair-pin loop
arrangement
preserves
medullary
osmolarity
Cortex
Medulla
The 3 Essential Elements:
1) Active Na+ transport in thick ascending limb of loop.
( Overall, the loop always reabsorbs more Na+ than H20 )
2) Unique arrangement of medullary peritubular capillaries.
( The vasa recta loop down into the renal medulla)

5. Origin of the Hyperosmotic Renal Medulla
Cortex
Medulla
mOsM
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Urea Recycling:
Keeps “dumping” urea
(solute) back into medulla.
Rate of “dumping” depends
on urea level in the tubular
fluid (faster when higher).
Urea
Recycling
The 3 Essential Elements:
1) Active Na+ transport in thick ascending limb of loop.
( Overall, the loop always reabsorbs more Na+ than H20 )
2) Unique arrangement of medullary peritubular capillaries.
( The vasa recta loop down into the renal medulla )
3) Recycling of urea between loop and collecting duct.
( Urea provides about half of the high medullary osmolarity )

6. Tubular Fluid Osmolarity Changes along Nephron
Percent filtered
H20 Remaining
Iso-osmotic
to plasma
Dilute
urine
Conc.
Approaches osmolatity of interstitium in cortex
Approaches osmolatity of interstitium in medulla
Hypo-osmotic
to plasma

7. Regulation of Sodium and Water Excretion
( Lecture 5 … page 66, renal syllabus )
….. essentially same as…..
Regulating Plasma Volume and Osmolarity
Kidneys excrete salt and water
Since the amounts of salt and water in body define blood volume & osmolarity,
Kidney’s control blood volume and body fluid osmolarity.

8. Renal Role in Blood Pressure Regulation
Short Term BP Control: seconds/minutes classic baroreceptor reflex
sympathetic output changes vascular resistance
Medium Term BP Control: minutes/hours renin release
renin promotes angiotensin II formation
circulating angiotensin II changes vascular resistance
Long Term BP Control: hours/days changes in total body salt & H20
changes blood volume
The Kidney’s Role:
1) renin release (min/hrs)
2) controlling blood volume (hrs/days)
CONCEPT: If you control Na, then you control blood volume.
Blood volume changes when H20 moves in or out of the plasma.
H20 always moves down osmotic gradients.
Most abundant osmotically active particle in plasma is Na+.
Control of Na = control of H20 movement = Control of volume

9. Regulation of Na+ & H20 Balance
First a Conceptual Overview
Parallel Bulk
Handling
Pressure
Natriuresis
Aldosterone ….. Na
ADH ….. H20
Differential
Hormonal
Fine-Tuning

10. Regulation of Na+ Balance
Pressure Natriuresis
Definitions:
Natriuresis =  Na+ excretion in Urine
Pressure Natriuesis is caused
by increased blood pressure
& associated increase in GFR.
More IN
OUT
Simply Hemodynamics:
More IN = More OUT
No independent treatment of Na+ & H20
Good for simple bulk volume control
Some Murky Mechanism Details:
Some evidence that increased BP some
how down regulates Na reabsorption
from the proximal tubule
Higher hydrostatic pressure in peritubular
capillaries reduces reabsorption from
the proximal tubule.
Pressure Natriuresis:
1) driven by simple hemodynamics
2) proximal nephron phenomenon
3) no sensors or circulating factors

11. Regulation of Na+ in Distal Nephron
Aldosterone:
Most important “H20-independent” controller
of Na+ reabsorption & Na+ balance
Steroid hormone produced by adrenal cortex
Acts on principle cells of the collecting duct
Circulating Angiotensin II stimulates its release
Differential Hormonal Fine-Tuning
Collecting Duct
So…  BP trigger baroreceptor response
… this in turn triggers renin release
… renin leads to increased angiotensin II levels
… this triggers aldosterone release
… this stimulates Na reabsorption
… this leads to increased blood volume
… increased blood volume leads to  BP
This is summarized in the next figure.

12. …  BP triggers baroreceptor response
…  BP & sympathetic inputs trigger renin release from granular cells
… renin enters circulation and leads to increased angiotensin II levels
… angiotensin II triggers aldosterone release from adrenal cortex
… aldosterone stimulates Na reabsorption from collecting duct
… the retained Na leads to increased blood volume which raises BP
Aldosterone is not the only hormone that
regulates the body’s Na+ balance.

13. Atrial Natriuretic Peptide released from heart when
atria stretch due to high
blood volume ( BP)
vasodilates afferent arteriole
increasing GFR
inhibits Na reabsorption in
from collecting duct
inhibits renin-angiotensin
Atrial Natriuretic Peptide
Now….
Let’s look at hormonal
control H20 balance

14. Regulation of H20 Balance
Key Hormone = Antidiuretic Hormone (ADH) sometimes called vasopressin
Collecting Duct
ADH :
Peptide hormone
Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly
Released from posterior pituitary
Increases H20 Permeability of apical
membrane by promoting the fusion
of vesicles containing an aquaporin

15. Input Signals that Control ADH Release
1) cardiovascular baroreceptors
 BP  less baroreceptor firing   ADH release
 BP  more baroreceptor firing   ADH release
2) hypothalamic osmoreceptors
 plasma osmolarity   ADH release
 plasma osmolarity   ADH release

16. Input Signals that Control ADH Release
1) cardiovascular baroreceptors
 BP  less baroreceptor firing   ADH release
 BP  more baroreceptor firing   ADH release
2) hypothalamic osmoreceptors
 plasma osmolarity   ADH release
 plasma osmolarity   ADH release
Baroreceptors

17. Input Signals that Control ADH Release
1) cardiovascular baroreceptors
 BP  less baroreceptor firing   ADH release
 BP  more baroreceptor firing   ADH release
2) hypothalmic osmoreceptors
 plasma osmolarity   ADH release
 plasma osmolarity   ADH release
Osmoreceptors
The cells that
release ADH integrate
the 2 input signals.
“2 heads are better than 1”

18. Input Signals that Control ADH Release
1) cardiovascular baroreceptors
 BP  less baroreceptor firing   ADH release
 BP  more baroreceptor firing   ADH release
2) hypothalmic osmoreceptors
 plasma osmolarity   ADH release
 plasma osmolarity   ADH release
Generally, osmolarity usually dominates unless there are
very large changes in volume.
Certain other brain level inputs can alter short-term ADH release (fear, pain, alcohol).
Diabetes insipidus is due to
abnormal ADH regulation.
Origin could be brain problem
or bad renal ADH receptors.

19. Free Water Clearance (CH20)
means to access renal H20 handling, not the usual clearance calculation
The CH20 determination considers urine as having 2 parts:
Urine
Volume
solute-free
H20
H20 with
solute
 This is the H20 “cleared”
Volume in which solutes
present would be iso-osmotic
compared to plasma. v
solute-free
H20
H20 with
solute
Can be calculate as
Osmolar Clearance
COSM =
UOSM · V
POSM

20. Free Water Clearance (CH20)
means to access renal H20 handling, not the usual clearance calculation
The CH20 determination considers urine as having 2 parts:
Urine
Volume
solute-free
H20
 This is the H20 “cleared” v
H20 with
solute
Volume in which solutes
present would be iso-osmotic
compared to plasma.
solute-free
H20
Thus…. CH20 = V - COSM
COSM =
UOSM · V
POSM
H20 with
solute
Can be calculate as
Osmolar Clearance

21. Free Water Clearance (CH20)
means to access renal H20 handling, not the usual clearance calculation
The CH20 determination considers urine as having 2 parts:
Urine
Volume
solute-free
H20
 This is the H20 “cleared” v
H20 with
solute
Volume in which solutes
present would be iso-osmotic
compared to plasma.
Note: CH20 could
be negative !!
This is when very
concentrated
urine is being
produced.
solute-free
H20
Thus…. CH20 = V - COSM
COSM =
UOSM · V
POSM
H20 with
solute
Can be calculate as
Osmolar Clearance

22. Free Water Clearance (CH20)
means to access renal H20 handling, not the usual clearance calculation
The CH20 determination considers urine as having 2 parts:
Urine
Volume
solute-free
H20
H20 with
solute
 This is the H20 “cleared”
Volume in which solutes
present would be iso-osmotic
compared to plasma. v
Note: CH20 could
be negative !!
This is when very
concentrated
urine is being
produced.
solute-free
H20
H20 with
solute
Can be calculate as
Osmolar Clearance
COSM =
UOSM · V
POSM
Thus…. CH20 = V - COSM
If… V = COSM
Then… CH20
is zero
If… V > COSM
Then… CH20
is positive
If… V < COSM
Then… CH20
is negative