FRESH AIR INTAKE EXHAUST FUMES

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100

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350o

o

o o

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INSULATION

FURNACE

THE COUNTERCURRENT PRINCIPLE

COUNTERCURRENT: LOOP OF HENLE

80010021000

alh

200402400dlh

The Countercurrent Multiplier

cortexm

edul

laH2O

1200

285 100

502

802

11021100

500 300

900

600800

salt

THE COUNTERCURRENT SYSTEM

THE LOOP OF HENLE: Adds more salt than water to the medullary interstitium, thereby osmotically concentrating the interstitial fluid and diluting the tubular fluid.

cortexm

edul

la

H2O

285 100

502

802

11021100

500 300

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600800

salt

1202 1200

175cortex

502

802

1102

distal tubule

500

800

285

100

1100

300H2O

300

DISTAL AND CORTICAL COLLECTING TUBULES

THE COUNTERCURRENT SYSTEMTHE LOOP OF HENLE: Adds more salt than water to the medullary interstitium, thereby osmotically concentrating the interstitial fluid and diluting the tubular fluid.

THE DISTAL TUBULE AND CORTICAL COLLECTING TUBULE: Lose more water than salt to the cortical interstitium, bringing the tubular fluid back to an isosmotic state before delivering it the medullary collecting duct. Thus the solute-free water generated in the loop of Henle is returned to the circulation and does not enter the medullary interstitium.

MEDULLARY COLLECTING TUBULES

10028001000

1000

1002

402

dlh alh

200400

400cd

402

cortex

med

ulla

H2O

285 100

502

802

11021100

500 300

900

600800

salt

1202 1200

175cortex

502

802

1102

distal tubule

500

800

285

100

1100

300H2O

300

THE COUNTERCURRENT SYSTEM

THE LOOP OF HENLE: Adds more salt than water to the medullary interstitium, thereby osmotically concentrating the interstitial fluid and diluting the tubular fluid.

THE DISTAL TUBULE AND CORTICAL COLLECTING TUBULE: Lose

more water than salt to the cortical interstitium, bringing the tubular fluid back to an isosmotic state before delivering it the medullary collecting duct. Thus the solute-free water generated in the loop of Henle is returned to the circulation and does not enter the medullary interstitium.

THE MEDULLARY COLLECTING DUCT: Surrounded by the osmotically concentrated medullary interstitium, the duct loses more water than solute, thereby bringing the tubular fluid to the same high osmotic concentration as the interstitium.

COUNTERCURRENT: VASA RECTA

80010021000

1000

1010

200402400

400

440

avr

dvr

alhdlh

The Countercurrent Exchanger

285 350

502

802

med

ulla

1102

800

500

1100

820

1110

535

H2O saltcortex

400

1000

cd

THE COUNTERCURRENT SYSTEMTHE LOOP OF HENLE: Adds more salt than water to the medullary interstitium, thereby osmotically concentrating it and diluting the tubular fluid.

THE DISTAL TUBULE AND CORTICAL COLLECTING TUBULE: Lose more water than salt to the cortical interstitium, bringing the tubular fluid back to an iso-osmotic state before delivering it the medullary collecting duct. Thus the solute-free water generated in the loop of Henle is lost to the circulation without entering the medullary interstitium.

THE MEDULLARY COLLECTING DUCT: Surrounded by the osmotically concentrated medullary interstitium, the duct loses more water than solute, thereby bringing the tubular fluid to the same high osmotic concentration as the interstitium.

THE VASA RECTA: The descending vasa recta loses water to concentrated plasma in the ascending vasa recta, thereby reducing the volume of water carried to the deep reaches of the medullary interstitium. The plasma gains salt as it descends into the medulla but subsequently returns it again to the blood in the descending vasa recta, perserving the salt content of the medullary interstitium.

THE COUNTERCURRENT SYSTEM

1200

H2O

285 100

502

802

11021100

500 300

900

600800

salt

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175

502

802

1102

500

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1100

300285 350

502

802

1102

500

1100

820

1110

535

H2O salt

800

SUMMARY OF THE COUNTERCURRENT MECHANISM

♦ The primary engine is active salt reabsorption without water by the thick ascending limb of Henle’s loop.

♦ The countercurrent flow arrangement of Henle’s loop and the vasa recta traps salt and urea within the medulla and minimizes the volume of water entering the medullary interstitium.

♦ The resulting high osmotic concentration of the medullary interstitium causes water reabsorption from the collecting tubule, raising the osmotic concentration of the urine.

FACTORS AFFECTING COUNTERCURRENT SYSTEM♦ ADH controls the permeability of the collecting tubule to water.

♦ Increased flow rate through the ascending limb of Henle’s loop increases salt reabsorption and effectiveness of the CC system.

♦ Increased flow rate through the medullary collecting tubule delivers additional water to medulla reducing the osmotic concentration of the medulla and thereby reducing the osmotic concentration of the urine.

♦ Increased flow rate through vasa recta depletes medullary ISF of solute.

♦ Insufficient protein intake can reduce supply of urea and decrease effectiveness of CC system.

♦ Drug effects: Loop diuretics inhibit primary engine of CC system. Amiloride, thiazides and aldosterone inhibitors increase flow rate through medullary collecting tubules.

♦Anatomical: Among species, the fraction of nephrons with long loops and the relative length of the loops affect the CC system.

UREA REABSORPTION AND SECRETION

▲Urea reabsorption and secretion occurs by a process of facilitated diffusion via specialized channels or carriers in the tubular cell membranes.

▲It is driven by a urea chemical gradient created by water reabsorption.

▲Urea is concentrated in the medullary interstitium. This enables the kidney to excrete urea at a high concentration in the urine.

▲At the same time the high urea concentration in the medullary interstitium contributes to the process of osmotically concentrating the urine.

EFFECT OF FLOW RATE ON UREA EXCRETION

FRACTIONAL EXCRETION OF UREA

URINE FLOW, L/24 hrs

U/P

UR

EA/U

/PC

R

0 2 4 6 8 10 12 0.0

0.2

0.4

0.6

0.8

1.0

TUBULAR HANDLING OF UREA

H2OUrea

Urea?

UreaUt2

UreaUt4Ut1

COUNTERCURRENT CONCENTRATION OF UREA

1100

502

802

1202

1102

1200

500

285

1200

285

502

802

1102

500

800

1100

300

900

600800

UREA

H2O

vasa recta

ureaH2O

urea

100

outerinnermedulla

1100

+

REGULATION OF PLASMA OSMOTIC CONCENTRATION

_

ECFosm OSMO-RECEPTORS

ADH

H2O

Uosm + V

+

0

1

2

3

4

5

6

275 280 285 290 295 300

ADHpg / ml

PLASMA OSMOLALITY, mOSM / Kg H2O

MAX. EFFECTIVE CONC.

BASAL

TRESHOLD

CONTROL OF ADH SECRETION

ADH attaches to a V2 receptor and activates a cascade through a Gs protein, adenylyl cyclase, cAMP and protein kinase A to cause the insertion of aquaporin 2 into the apical membrane.

H2O moves through aquaporin 2 in response to the osmotic gradient and thence through aquaporins 3 and 4 in the basolateral membrane.

MECHANISM OF ACTION OF ADH

WATER CONSERVATION Consider that a person excretes approximately 600 mOsmoles and 2.0 L of H2O a day. The urine osmotic concentration will average 300 mOsm/L.

Since the plasma osmotic concentration is approximately 300 mOsm/L, the kidney is excreting an isosmotic urine. The clearance of osmoles, Cosm, can be calculated:

Cosm= (UosmV)/Posm = (300 mOsm/L x 2 L/day)/300 mOsm/L = 2 L/day.

If that person is deprived of fluid but maintains the same solute intake, water will be reabsorbed to a greater extent and the urine osmotic concentration may rise to 1200 mOsm/L. Solute excretion(UosmV) will still equal 600 mOsmoles/day and Cosm will still equal 2 L/day. However urine volume will equal only 0.25 L/day. We canconsider that 1.75 L of water was reabsorbed without solute.

That volume of H2O that is reabsorbed to raise the urine conc. above that of plasma is called solute free water reabsorption, TcH2O, and is calculated as follows.

TcH2O = Cosm – V = 2L/day –0.25 L/day = 1.75 L/day

WATER CONSERVATION

1202 1200

175cortex

med

ulla

502

802

1102

distal tubule

500

800

285100

1100

300

H2O

saltSolute-free water reabsorption begins in the collecting tubule at the cortical-medullary junction and continues in the outer and inner medullary CD when ADH is present and the tubular wall is permeable to ADH.

The volume of TcH2O is dependent upon the efficiency of the counter-current system and the magnitude of solute delivery to the collecting tubule.

WATER DIURESISConsider again a person taking in and excreting 600 mOsmoles of solute a day. If that individual drinks copious amounts of water, ADH secretion will be suppressed and the urine osmotic concentration may drop to as low as 50 mOsm/L and urine volume may rise to 12 L/day. Cosm will still equal 2 L/day.

The excess water excreted above that 2 L/day can be considered to be solute-free water cleared from the body.

CH20 = V – Cosm = 12 L/day –2 L/day = 10 L/day.

Solute-free water generation begins at the point in the thick ascending limb where the reabsorption of solute without water first lowers the urine osmotic concentration below that of plasma and continues in the distal tubule and collecting duct where solute reabsorption without water reabsorption continues in the absenceof ADH.

Time Posm V Uosm UosmV Cosm CH2OMin mOsm/kg ml/min mOsm/kg mOsm/min ml/min0 Empty bladder and begin 1st clearance period.

60 End 1st clearance period and collect blood sample.290 0.54 1034 558.4 1.93 -1.39

62-69 Subject drinks 1200 ml water.130 Empty bladder and begin 2nd clearance period.160 End 2nd clearance period and collect blood sample.

283 11.0 82 902 3.19 7.81220 Empty bladder and begin 3rd clearance period.250 End 3rd clearance period and collect blood sample.

288 1.1 490 539 1.87 -0.77

EFFICIENCY OF WATER DIURESIS

SOLUTE DIURESISCAUSES:Presence in the filtrate of large amounts of poorly reabsorbed solute.Inhibition of a transport system.

TUBULAR REACTION:In the proximal tubule, the presence of the poorly reabsorbed solute inhibits salt and water reabsorption because the high conductance and water permeability prevent the establishment of high gradients across the tubular epithelium.

The increased flow rate through the thick ALH allows additional salt reabsorption because of the gradient effect. This partially compen-sates for the proximal inhibition.

In the distal tubule and CD the increased flow rate also allows additional solute and water reabsorption.

In the medullary CD, water reabsorption initially increases but,ultimately, the additional water entering the medullary interstitium washes out the countercurrent gradient.

EFFECT OF FLOW RATE ON SALT REABSORPTION

Uosm

TcH2O

Flow Rate

SOLUTE DIURESIS

Time Hct GFR V Posm Uosm Pna Una UnaV UosmV TH2OMin % mlmin mosmole/kg mEq/l μEq/min μosmole ml/min

/min0 Begin I.V. infusion of saline at 1.4 ml/min.25 Begin 1st clearance period50 End 1st clearance period

45 25 0.13 292 1954 145 278 36.1 254 0.7452 Begin infusion of 20% mannitol at 5 ml/min I.V.80 Begin 2nd clearance period.90 End 2nd clearance period.

38 26 3.3 321 425 133 52 172 1402 1.07

AN EXAMPLE OF SOLUTE DIURESIS