The document discusses countercurrent exchange systems in various organs and tissues of the body including the kidney. It describes how the countercurrent multiplier system in the loop of Henle establishes a gradient that is maintained by the countercurrent exchanger system of the vasa recta, allowing the kidney to produce concentrated urine through the medullary countercurrent system. It also discusses how diuretics work by targeting different sites along the nephron to increase urine output.

1. Dr.

2.  A system in which the inflow runs parallel to,
counter to, and in close proximity to the outflow
for some distance.
Conditions to be fulfilled,
 2 tubes in parallel
 movement in opposite direction
 in close proximity & selectively permeable

3. Maintenance of air temperature in a
furnace
Countercurrent mechanism helps Penguin
to stand on ice for long time.

4.  Skin (heat conservation)
 Scrotum (exchange of heat & testosterone)
 Kidney – ability to concentrate urine,
a critical adaptation of life on
land through evolution

5.  Depends upon maintenance of a gradient
of increasing osmolality along the
medullary pyramids.
 Counter current multiplication system-
Loop of Henle
 Counter current exchange system –
Vasa recta

6. • long loop of Henle establishes a vertical osmotic
gradient (Countercurrent multiplier)
• their vasa recta preserve this gradient while
providing blood to renal medulla (
Countercurrent exchanger)
• collecting ducts of all nephrons use the gradient in
conjunction with the hormone vassopressin, to
produce urine of varying concentration (osmotic
equilibrating device)
 Collectively this entire functional organization is
known as medullary countercurrent system

8.  A large, vertical osmotic
gradient is established in
the interstitial fluid of the
medulla
(from 100 to 1200
mosm/liter)
 This osmotic gradient
exists between
the tubular lumen and
the surrounding
interstitial fluid.

9.  Process in which small osmotic gradient
established at any level of LOH is multiplied in to
larger gradient.
 Single effect
 Active transport of Na & Cl out of thick ascending
limb
 High permeability of thin descending limb to
water
 Solute deposition in medulla & removal of water
from descending limb

10. PCT
Water reabsorption
follows solute
reabsorption
Descending limb of loop of
Henle
Highly permeable to water
Relatively impermeable to
solutes
Thick Ascending
limb
Impermeable to
water
Solute reabsorption
occurs

11.  Hypothetical case
 Assume glomerular
filtrate to be 300
mOsm/L
 Assume Medullary
interstitium to be at
300 mOsm/L
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300

12.  Transporters
create a gradient
of
200 mOsm/L
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300

13.  The osmolarity in
the medullary
intersitium
increases to 400
mOsm/L
300
300
300
300
300
300
200
200
200
200
200
200
400
400
400
400
400
400

14.  The descending
limb loses water
and reaches the
same osmolarity
400
400
400
400
400
400
200
200
200
200
200
200
400
400
400
400
400
400

15.  New fluid enters
the loop of Henle300
300
300
400
400
400
200
200
200
400
400
400
400
400
400
400
400
400

16.  Upper
interstitium
equilibrates
300
300
300
400
400
400
200
200
200
400
400
400
300
300
300
400
400
400

17. 300
300
300
400
400
400
200
200
200
400
400
400
300
300
300
400
400
400
Transporters
pump out
sodium and
chloride again
into interstitium

18. Until a gradient of
200 mosm is
attained
300
300
300
400
400
400
150
150
150
300
300
300
350
350
350
500
500
500

19.  Descending limb
equilibrates350
350
350
500
500
500
150
150
150
300
300
300
350
350
350
500
500
500

20.  Inflow of fresh
filtrate and
equilibration with
the medullary
interstitum
300
300
350
350
500
500
150
150
300
300
500
500
300
300
350
350
500
500

21.  Tranporters work
again to reach a
gradient of 200
mosm
 Process is repeated
again and again
 Thus a single effect
gets multiplied
300
300
350
350
500
500
125
125
225
225
400
400
325
325
425
425
600
600

22.  Axial gradient
Magnitude depends on,
 Rate of fluid flow
 Strength of single effect
 Length of LOH

23.  Descending limb is highly permeable to water
but impermeable to solutes
 Thin ascending limb is passively permeable to
solutes
 In thick ascending limb, Na & Cl are actively
transported (Na/K/2Cl)

25.  Solute gradient created by LOH in medulla is
maintained by vasa recta
 Decrease solute dissipation
 In descending limb, solutes diffuse into vessels
 In ascending limb, solutes diffuse out of vessel
 Thus solutes keep circulating
 Water diffuses out of descending limb and into
ascending limb
 While solutes recirculate in medulla, water is
removed from it

27.  Descending vasa recta
• Loses water
• Gains solutes
 Ascending vasa recta
• Gains water
• Loses solutes

28.  Acts as osmotic equilibrating device, by its
permeability to water & urea
 use the gradient, created by LOH &
maintained by vasa recta, in conjunction
with the hormone vasopressin, to produce
urine of varying concentration

30.  Vasopressin-controlled, variable water reabsorption
occurs in the final tubular segments.
 65% of water reabsorption is obligatory in the proximal
tubule. In the distal tubule and collecting duct it is
variable, based on the secretion of ADH.
 The secretion of vasopressin increases the permeability
of the tubule cells to water. An osmotic gradient exists
outside the tubules for the transport of water by osmosis.
 Vasopressin works on tubule cells through a cyclic AMP
mechanism.
 During a water deficit, the secretion of vasopressin
increases. This increases water reabsorption.
 During an excess of water, the secretion of vasopressin
decreases. Less water is reabsorbed. More is
eliminated.

32. Every time tubular fluid passes through LOH,
 Water comes out of descending limb into interstitium,
which is removed by ascending limb of vasa recta
 Solutes come out of ascending limb into interstitium
Thus, high osmolality is maintained in medulla
 This causes movement of water out of the
Collecting Duct & makes the urine concentrated

33. DIURETICS
drugs that increase the rate of urine flow
their clinical applications aim to reduce ECF
volume by decreasing total body NaCl content

34. TYPE Site of
Action
Examples
1. Inhibitors of Carbonic
Anhydrase
PCT Acetazolamide,
Methazolamide
2. Osmotic diuretics LOH Glycerine,
Isosorbide,
Mannitol,Urea
3. Inhibitors of Na-K-2Cl
symport
(Loop diuretics /High
ceiling diuretics
Thick AL of
LOH
Furosemide,
Bumetamide,
Torsemide

35. TYPE Site of
Action
Examples
4. Inhibitors of Na-Cl
symport
(Thiazide-like
diuretics)
DCT Chlorothiazide,
Hydrochlorothiaz
ide,
5. Inibitors of renal
epithelial Na channels
(K-sparing diuretics)
Late DCT
& CD
Amiloride,
Triamterene
6. Antagonists of
mineralocorticoid
receptors
(Aldosterone
antagonists/
K-sparing diuretics)
Late DCT
& CD
Spironolactone

36. Diuretic Braking
Compensatory Mechanisms:
 Activation of sympathetic nervous system
 Activation of R-A-A axis
 Decreased arterial BP
 Hypertrophy of renal epithelial cells
 Increased expression of renal epithelial
transporters