COUNTERCURRENT

MECHANISM
 Introduction
• Kidney posses unique property of regulating the volume &
osmolality of urine.

• water excess : Kidney can excrete urine with an osmolarity as

low as 50mosm/L

• water deficit : kidney can excrete urine with a concentration

of 1200 to 1400mosm/L

• Without major changes in rate of excretion of sodium &

potassium .
 Principal factors
• Responsible for concentration and dilution of urine

a. Antidiuretic hormones

b. Hyperosmolality and osmolality gradient in

medullary interstitium
 Renal mechanisms for excreting a
dilute urine
• Kidney can excrete as much
as 20L/day of dilute urine
with a concentration low as
50mOsm/L.

• Reabsorbing solutes

• Fail to reabsorb water in

distal tubule & collecting
ducts.
Renal mechanisms for excreting a dilute urine
• Glomerular filtrate
osmolarity is same as
plasma of 300mOsm/L

• Tubular fluid remains

isosmotic in proximal
tubule

• Descending loop of Henle ,

water is reabsorbed by
osmosis hypertonic about
2to 4 times
• In ascending limb especially
the thick segment , Na+,
K+, Cl- are avidly
reabsorbed

• This part of tubule is

impermeable to water

• Tubular fluid is dilute

• Osmolarity decreases to
100mOsm/L
Thus, Regardless of whether ADH is present or absent , fluid leaving the early
distal tubular segment is hypo-osmotic, with an osmolarity of only one third the
osmolarity of plasma
 Renal mechanisms for excreting a
dilute urine
• Late distal convoluted tubule , cortical collecting duct
& collecting duct impermeable to water in the
absence of ADH

• Additional reabsorption of solute.

• Osmolarity decrease to 50mOsm/L.

• Failure to reabsorb water & continued reabsorption of

solutes leads to large volume of dilute urine.
 Renal mechanisms to conserve water by
excreting concentrated urine
• Ability of kidney to form more concentrated urine than
plasma , essential for survival

• Water deficit , form concentrated urine by excreting solutes

&↑ water reabsorption.

• Kidney , produce maximal urine concentration of 1200 to

1400mOsm/L.( 4 to 5 times the osmolality of plasma)
 Obligatory urine volume
• Minimal volume of urine that must be excreted

• 7okg human must excrete about 600mOsm of solutes

each day.

• Max urine concentrating ability 1200mOsm/L

• Obligatory urine volume = 600mosm/day

1200mOsm/day
= 0.5L/day
 Renal mechanisms to conserve water by
excreting concentrated urine
• Basic requirement
a. High level of ADH - ↑ permeability of distal tubules
to water

b. High osmolarity of renal medullary interstitial fluid

- provides osmotic gradient necessary for water
reabsorption in presence of high ADH.
( by Counter current mechanism )
 Differences between cortical and juxtamedullary
nephron
Feature Cortical nephron Juxtamedullary nephron
Location of glomerulus Upper region of cortex Junction of cortex and
medulla.
Percentage of total 85% 15%
nephrons
Size of glomeruli Small Larger
Size of loop of Henle Small , extend up to outer Large, extend deep into
layer of medulla the medulla
Descending limb of loop Thin segment Thin segment
of Henle comprises
Ascending limb of loop of Thick segment Thin segment
Henle comprises
Efferent arterioles Have larger diameter & Have smaller diameter, &
break up into peritubular continues as vasa recta.
capillaries
Feature Cortical nephron Juxtamedullary nephron
Rate of filtration Slow High

Major function Excretion of waste Concentration of urine

products of urine by counter current
mechanism
 Counter current mechanism produces a Hyper
osmotic renal medullary interstitium

• The osmolarity of interstitial fluid in almost all parts of the

body is 300mOsm/L, similar to plasma osmolarity.

• Osmolarity of interstitial fluid in medulla of kidney 1200 to

1400mOsm/L ( accumulation of solutes in excess of water)
 Counter current mechanism
• Factors contributing to solute concentration

i. Active transport of Na+ & co transport of K+ , Cl- out of

thick portion of ascending limb of loop of Henle into
medullary interstitium

Pump establishes 200mOsm concentration gradient between

tubular lumen & medullary interstitium ( thick limb is
impermeable to water)

ii. Active transport of ions from collecting ducts into medullary

interstitium
 Counter current mechanism
iii. Facilitated diffusion of large amounts of urea from inner
medullary collecting ducts to medullary interstitium.

iv. Diffusion of small amounts of water from medullary tubules

into medullary interstitium.
 Counter current mechanism
First step
• loop of Henle filled with
fluid with concentration of
300mOsm/L
 Counter current mechanism
Step 2. Active pumping of
thick ascending limb turned
on.

• ↑ interstitial concentration

• Establishes 200mOsm/L
concentration gradient
 Counter current mechanism
• Step 3
• Tubular fluid in descending
limb of loop of Henle and
interstitial fluid reach
osmotic equilibrium .

• Interstitial osmolarity is
maintained at 400mOsm/L
(continued transport of ions
out of thick ascending
limb)
Step 4
• Additional flow of fluid into
the loop of Henle
• Hyperosmotic fluid flows
into the ascending limb.

• Additional ions are pumped

into the interstitium leaving
water causing an osmolality
of 200mOsm/L.

• ↑ interstitial osmolality to
500mOsm/L
 Counter current mechanism

Fluid in the descending limb reaches

Interstitial osmolality to equilibrium with hyper osmotic
500 mOsm/L medullary interstitium
 Counter current mechanism

Hyper osmotic tubular fluid from descending limb flows into ascending limb ,
more solutes are continuously pumped out of tubules into medullary
interstitium
• Traps solutes in medulla and multiplies the concentration
gradient established by active pumping of ions out of thick
limb of loop of Henle.

• Raising the interstitial osmolarity to 1200 to 1400mOsm/L

• Repetitive reabsorption of NaCl by thick limb of loop of

Henle & inflow of new NaCl from proximal tubule is called
counter current multiplier system
Counter current multiplier system
Role of distal tubule and collecting ducts in
excreting a concentrated urine
• Tubular fluid reaches the distal convoluted tubule in renal
cortex , fluid is dilutes 100mOsm/L

• Cortical collecting tubule , water reabsorption dependent on

ADH (impermeable to water & reabsorb solutes)

• Water is reabsorbed into cortex , than into medulla , preserves

the high medullary interstitial fluid osmolarity.

• Minimal water reabsorption occurs in the medulla quickly

carried by vasa recta into venous blood.
Role of distal tubule and collecting ducts in
excreting a concentrated urine
 Contribution of Urea to hyper osmotic medullary
interstitium and to a concentrated urine.

• Contributes about 40 to 50 % of osmolarity (500- 600mOsm/L)

• Passively reabsorbed from the tubule

• Proximal tubule 40-50% of filtered urea reabsorbed

• Urea is not permeable as water.

• Concentration ↑in thin segment of loop of Henle ( permeable to

water) & secretion occurs from medullary interstitium
Additional mechanism for forming hyper osmotic renal
medulla
• Thick asc limb , distal tubule , cortical collecting tubule are
relatively impermeable to urea ( little reabsorption occurs)

• Urea concentration ↑due to high levels of ADH

• High tubular fluid concentration of urea flows into inner

medullary collecting duct, urea reabsorbed by urea
transporters.

• Diffuses into the inner medullary interstitium & then into

thin loop of Henle.

• Urea recirculates several times before it is excreted

Countercurrent exchange in Vasa recta
• Preserves hyperosmolality of renal medulla.

• 2 special features of renal medullary blood flow that

contribute to preservation of high solute concentration

i. Medullary blood flow is low (< 5% of total renal blood flow)

sluggish blood flow , maintain metabolic needs & minimises
solute loss from medullary interstitium.

ii. The Vasa recta serves as countercurrent exchangers,

minimizes washout of solutes from medullary interstitium
Large amount of solutes would be lost from renal medulla
without the U shape of Vasa Recta capillaries
 Countercurrent exchange in Vasa recta
• Large amount of solute & fluid exchange occurs , little net
dilution of concentration in renal medulla ( U- shaped capillaries)

• Vasa recta do not create the medullary

hyperosmolarity, but prevent it from being dissipated.
 Disorders of urinary concentrating
ability
1.Inappropriate secretion of ADH

2. Impairment of countercurrent mechanism

3. Inability of distal tubule, collecting tubule, and

collecting ducts to respond to ADH.
 Antidiuretic hormone
• Release by stimulation of osmoreceptors located in
hypothalamus

• Second neuronal area – anteroventral region of third

ventricle (AV3V region )
- subfornical organ
- organum vasulosum of lamina terminalis
LESION
- median preoptic nucleus

Affect ADH secretion, thirst, sodium appetite, blood

pressure
 Disorders of urinary concentrating
ability
• 1.Inappropriate secretion of ADH

i. Failure to produce ADH: “ Central” Diabetes insipidus

- head injuries, infections, congenital
- large volume of dilute urine , exceed 15L/day
- severe dehydration
Treatment : Desmopressin – synthetic analog of ADH
(injections, nasal spray, orally )
 Disorders of urinary concentrating ability

• 1.Inappropriate secretion of ADH

ii. Inability of kidneys to respond to ADH: “Nephrogenic”

diabetes insipidus

- failure of the counter current mechanism to form

hyperosmotic medullary interstitium

- Failure of distal & collecting tubules to respond to ADH

- Large volume of dilutes urine are formed

 Disorders of urinary concentrating ability
• Others

i. Damage to renal medulla

ii. Impaired functioning of loop of Henle ( diuretics)

iii. Drugs – lithium , tetracyclines (impair the distal

nephrons to ADH)