CONCENTRATION OF URINE-

COUNTERCURRENT MECHANISM

DR.NEETHU SHOWKATH
 Kidneys have the capability to pass urine with extremes of osmolality
ranging from 30 mOsm/kg to 1400 mOsm/kg of H2O

 Though GFR is 180 L/day, only about 1.5 L of urine is excreted daily

 Thus, kidney normally excretes a concentrated urine to prevent

volume depletion from the body
Osmolarity of fluid in different segments of tubule
Requirements for excreting a concentrated
urine
 A) High level of ADH – increases the permeability of DCT & CD to
reabsorb water

 B) High osmolarity of renal medullary interstitial fluid

What is the process by which renal medullary ISF becomes
hyperosmotic ?

 COUNTERCURRENT SYSTEM
Countercurrent mechanism produces a Hyperosmotic Renal
Medullary Interstitium

 Osmolarity of ISF in almost all parts of body is about 300mOsm/L

 Osmolarity of ISF in the medulla of kidney is much higher –

increasing progressively to 1200-1400mOsm/L in the pelvic tip of
medulla

 This means that the renal medullary interstitium has accumulated

solutes in great excess of water
Major factors causing the buildup of solute conc. in renal
medulla are:

 1. Active transport of sodium & co-transport of potassium & chloride out of

thick ascending limb of LOH into interstitium (via Na+-K+2Cl- symporter)

 2. Active transport of ions from CDs into medullary interstitium

 3. Facilitated diffusion of large amounts of urea from inner medullary CDs into
medullary interstitium

 4. Diffusion of only small amounts of water from medullary tubules into

medullary interstitium
Steps involved in causing Hyperosmotic Renal Medullary
Interstitium

 First, assume that the LOH is filled with fluid with a conc. of
300mOsm/L (same as that leaving PCT) – step 1
 Next, the active pump of Thick AL turned on, reducing conc. inside
tubule & raising the interstitial conc.
 This pump establishes a 200mOsm/L conc. gradient between tubular
fluid & the interstitial fluid - step 2
 The limit to the gradient is about 200mOsm/L – because- paracellular
diffusion of ions back into tubule counterbalances transport of ions
out of the lumen when the 200mOsm/L gradient is achieved
STEP-3
 Tubular fluid in the Descending Limb (DL) of LOH & the ISF
quickly reach osmotic equilibrium due to osmosis of water out of
DL

 The interstitial osmolarity is maintained at 400mOsm/L because of

continued transport of ions out of Thick AL
STEP- 4
 Additional flow of fluid into LOH from the proximal tubule

 Hyperosmotic fluid previously formed in the Desc.limb flows into

Asc.limb
STEP-5
 Additional ions are pumped into interstitium, with water remaining
behind until a 200mOsm/L gradient is established

 Interstitial fluid osmolarity rises to 500mOsm/L

STEP-6
 Once again, fluid in the Desc. Limb reaches equilibrium with the
hyperosmotic medullary ISF

 As the hyperosmotic tubular fluid from the Desc Limb fows into Asc
Limb, still more solute is continuously pumped out of tubules &
deposited into medullary interstitium
STEP-7
 These steps are repeated over and over, with the net effect of
adding more and more solutes to medulla

 With time, this process gradually traps solutes in the medulla,

eventually raising the ISF osmolarity to 1200-1400mOsm/L
 Thus, the repetitive reabsorption of NaCl by the thick AL of LOH
& continued inflow of new NaCl from PCT into LOH is called
countercurrent multiplier system

 NaCl reabsorbed from the ascending LOH keeps adding to the newly
arrived NaCl, thus “multiplying” its conc. in medullary interstitium
Role of DCT & CDs in excreting concentrated urine

 When tubular fluid leaves LOH & enters DCT, fluid is dilute (100
mOsm/L)

 Early DCT further dilutes tubular fluid – as this segment actively transports
NaCl out of tubule but impermeable to water
 As fluid flows into cortical collecting tubule  amount of water
reabsorbed depends on ADH

 High conc of ADH large amounts of water reabsorbed from

cortical CT into cortex interstitium

 The fact that these large amounts of water are reabsorbed into
cortex, rather than into renal medulla, helps to preserve the high
medullary ISF osmolarity
ROLE OF UREA IN CONCENTRATION OF URINE

 Urea contributes to hyper osmotic renal medullary interstial fluid and

to concentrated urine. How ?

 Urea is absorbed in PCT – 50%

 50% urea comes to DCT and CT - which are not permeable to urea
but Collecting Duct in the inner medulla is permeable
ROLE OF UREA IN CONCENTRATION OF URINE- UREA
CYCLE

 When water is reabsorbed in DCT and CT under action of ADH, urea is

more concentrated

 Facilitated diffusion of urea occurs from CT in the inner medullary region

by specific urea transporters (UT-A1 & UT-A3) and contributes to the
concentration of medullary interstial fluid

 Increased urea present in the interstial fluid diffuses into loop of Henle
(descending and ascending limbs) and then to DCT and CT, therefore,
recirculates many times before it is excreted – called Urea Cycle
UREA CYCLE
Countercurrent Exchange System
 Countercurrent Exchange in Vasa Recta Preserves
Hyperosmolarity of Renal Medulla

 Without a special medullary blood flow system, the solutes

pumped into renal medulla by countercurrent multiplier system
would be rapidly dissipated
 2 special features of renal medullary blood flow that contribute to
preservation of high solute conc.
 1. Low medullary blood flow – accounting for <5% of total renal

blood flow
This sluggish blood flow is sufficient to supply the metabolic
needs
of tissues but helps to minimize solute loss from interstitium.
 2. U shape of Vasa Recta - serve as countercurrent exchangers,

minimizing washout of solutes from medullary intestitium

Mechanism of Countercurrent Exchange
 Blood enters and leaves medulla by way of Vasa Recta

 Vasa Recta, like other capillaries, are highly permeable to

solutes in blood, except for plasma proteins

 As blood descends into medulla towards papillae, it becomes

progressively more concentrated – partly by solute entry from
interstitium & partly by loss of water into interstitium
Mechanism of Countercurrent Exchange
 By the time blood reaches the tips of Vasa Recta, it has a conc.
of about 1200mOsm/L – same as that of medullary interstitium

 As blood ascends back towards cortex, it becomes

progressively less concentrated- as solutes diffuse back out into
medullary interstitium & as water moves into VR
Mechanism of Countercurrent Exchange
 Though large amounts of fluid and solute exchange occurs across
the vasa recta, there is little net dilution of concentration of
interstitial fluid at each level of renal medulla because of U shape
of Vasa Recta which act as countercurrent exchangers

 Thus Vasa Recta do not create the medullary hyperosmolarity,

but they do prevent it from being dissipated
IMPORTANT
 Loop of Henle – counter current multiplier - establishes the
concentration gradient in the medullary interstitial fluid.

 Vasa Recta – counter current exchanger- maintains the

concentration gradient in the medullary interstitial fluid.
COUNTER CURRENT MECHANISM
 Concentration of urine is due to

 1. Juxta medullary nephron – long loop of Henle establish (create) the vertical
osmotic gradient
 2. Vasarecta help to maintain (preserve) this osmotic gradient
 3. Collecting duct of all nephrons use the gradient along with hormone vasopressin
(ADH) to produce urine of varying concentration
 4. Urea also help in urine concentration mechanism

 This entire functional organization is known as medullary counter current system