Concentration of urine

Maj Dr Shavana R.L Rana

 Scheme of presentation

• Introduction
• Medullary Gradient
• Role of Loop of Henle
• Role of ADH
• Dilution and concentration of urine
 Introduction
• Osmolality and volume of the body fluid-
narrow range.
• Kidney plays a central role-vary the excretion
of water and solutes.
• Water intake and loss to be equal.
• Interaction of ADH secretion,thirst centres and
ability of kidneys to excrete urine
• Central role-henle’s loop.
• Range- 50-1200mOsm/kg H2O.
• Urine volume- 0.5-18L/day.
 Main factor
• Principal factors responsible for mechanism of
concentration and dilution of urine are:
• Antidiuretic hormone
• Hyperosmolality and osmolality gradient in
medullary interstitium of kidneys.
 Medullary Gradient
• Critical in concentartion of urine.
• Concentration of urine in presence of ADH requires
peritubular osmolality for absorption of water.
• Events-descending thin segment collecting duct
• Principle solute-NaCl and urea
• Formation of gradient-countercurrent
multiplication.
• Maintained by- countercurrent exchanger.
• Ranges-300mosm/kg of H20 in cortex
• 1200mOsm/Kg H20 in tip of papilla.
 Countercurrent multiplication
• Key factor- anatomic configuration of loop of
henle.
• Flow in opposite or countercurrent direction
in two limbs.
• Different Permeability and
transporter of the 2 limbs-
large osmotic gradient.
• In the kidney, the countercurrent system are
loop of Henle and the vasa recta.
• Countercurrent multiplier- loop of Henle and
is responsible for the production of
hyperosmolality and a gradient in renal
medulla and
• Countercurrent exchanger - vasa recta and is
responsible for maintenance of the medullary
gradient and hyperosmolality.
 Counter current multipliers

• The working of countercurrent multiplier, that

operates by two processes:
• Origin of single effect and
• Multiplication of the single effect.
 Single effect in outer medulla
• main driving force
• the osmotic gradient of approximately
200 mOsm that exists between the ascending limb of loop of
Henle and the surrounding interstitial fluid.
• juxtamedullary nephrons- medullary hyperosmolarity.
• thick ascending limb (TAL) of loop of Henle is located in the outer
medulla,
• impermeable to water and NaCl and other solutes are actively
absorbed in this segment without water, as a result, the tubular
fluid osmolality decreases to less than plasma.
• NaCl reabsorbed in this segment raises the osmolality of outer
medullary interstitium by about 200 mOsm.
 Single effect in inner medulla
• Passive transport of sodium ions from
ascending thin segment into the
interstitium(impermeable to water)
• Active transport of sodium from the inner
medullary collecting duct by principle cells
• Diffusion of urea from the collecting duct into
the medullary interstitium (when ADH
concentration is high in blood by employing a
specialized transport protein (UT-A)
 Multiplication of the single effect.

• The hyperosmolality and medullary gradient is in fact

generated by the multiplication of the single effect by the
countercurrent multiplier.
• The main characteristics of the components of
countercurrent multiplier
• High permeability of a descending thin segment to water.
• Impermeability to water but high permeability to NaCl.
• Impermeability to water and ability to actively absorb
solutes by thick ascending limb (TAL).
• In renal medulla, all other tubular structures (except
ascending limb) are in osmotic equilibrium.
 Countercurrent exchange
• Gradient Washed by blood flow.
• Medullary blood flow is 10% of RBF.
• Prevented by countercurrent flow in vasa recta.
• Special hair pin shaped capillaries.
• Highly permeable to water ,small solutes.
• Blood osmolality same as systemic plasma.
• Blood flows downward along increasing hypertonic
medullary interstitium.
• Water diffuses out.
• Solutes diffuses in.
•Osmolality of blood increases
at hairpin turn.
•Slightly below than
surrounding.
•As blood is rapid-small lag in
equilibration.
•No hairpin bend-capillary
would exit with the solutes.
•Blood ascends through region
of decreasing osmolality
• water fluxes in and solutes
fluxes out passively.
•In ascending limb blood
osmolality is always greater due
to a small lag.
 Role of ADH
• vasopressin.
• Acts on kidney.
• Regulates urine volume.
• Small peptide,
• 9 amino acid in length.
• Synthesized by neuroendocrine cells.
• Supraotic and paraventricular nuclei.
• Packaged-granule,transported via axons.
• Stored –nerve terminals in posterior pituitary.
• Regulators of ADHsecretion- osmolarity of body
fluids,volume and pressure of body system
• AQP2 on apical membrane.
• AQP3,4 on basolateral membrane.
• ADH increases urea permeability by increasing
UT action.
 Dilution of Urine
• ADH levels are low or zero- dilute
urine.
• Fluid entering descending thin
limb- iso-osmotic.
• Water reabsorbed.
• Thus,at the bend osmolality
equal to medullary fluid.
• Thin Ascending limb permeable
to NaCl and urea.
• NaCl diffuses out,urea diffuses in.
• Thick ascending limb-actively
reabsorbs NaCl.(diluting
segment)
• DCT & cortical collecting duct reabsorb NaCl.
• Absence of ADH ,water permeability is low.
• Medullary Collecting duct- even in absence of
ADH ,it is water and urea permeable.
• Therefor,some urea diffuses enters the
Collecting duct.
• Therefore,urine has osmolality of 50mOsm/kg
H20.
• Volume can be upto 18L/day.
 Concentration of urine
• In presence of ADH.
• Reabsorption of NaCl in thin and
thick ascending limb- increases
osmolality of medullary fluid.
• In DCT and collecting duct- water
reabsortion is increased.
• Cortical collecting duct-
300mOsm/kg H20.
• Due to filtered and reabsorbed urea.
• In medullary collecting duct-
osmolality increases upto
1200mOsm/kg H20.
• Due to increase water reabsorption.
• Volume can be as low as 0.5 L/day.
Thank you.