URINE CONCENTRATION

MECHANISMDr Mazlyn Mustapha

MB BCh BAO (Trinity College Dublin), MRCP (Ireland)Physiology Department

Universiti Sains Malaysia28th December 2008

Case History

A 25 year old man presented with a history of polyuria and polydipsia.

He has a history of being involved in a motor vehicle accident, where he suffered severe head injury as a result of not wearing a motorcycle helmet 2 years ago.

He had spent 2 months in hospital undergoing treatment and later underwent rehabilitation.

What is the diagnosis?

Question

How does the kidney produce urine with varying osmolality ( between 50-1200 mOsm/kg )?

Drink little bit – small volume of urine

Drink a lot – plenty of urine

Content

How the osmotic gradient (across medulla) is formed

How the counter current mechanism works

Collecting ducts impermeability to water unless there is ADH

The Osmotic Gradient

Between outer border renal medulla & papilla: osmolality of interstitium varies from 300 – 1200 mOsm/kg

The Gradient

There is countercurrent mechanism (bi-directional flow)

Gradient formation

Intially, all are iso-osmotic = 300 mOsm/kg

Thick ascending limb pumps NaCl into interstitium – at gradient of 200 mOsm/kg

Tubular fluid in descending limb equilibriates with interstitium

Gradient Formation

As tubular fluid in descending limb moves deeper, it brings the high osmolality deeper into the medulla

The hyperosmotic fluid enters the ascending limb, and more NaCl is pumped out

The osmolalility of the interstitium increases

This continues until the tubular fluid at the hair-pin end reaches 1000 mOsm/kg osmolality

Quick Summary

Kidney generates osmotic gradient by:

Active transport of NaCl from lumen into interstitium

Gradient is used to reabsorb water as it passes through medulla

Amount of water reabsorbed is controlled by ADH

More on the Gradient

Outer medulla: osmolality 290 mOsm/kg (NaCl)

Inner medulla: 1200 mOsm/kg (half – NaCl, half – urea)

Crucial factors for Gradient

Counter current arrangement

Na+ transport by thick ascending limb against gradient 200 mOsm/kg

Proximal tubule & descending limb – permeable to water & Na+, Cl+ & Urea

Crucial factors for Gradient

The thick ascending limb, the distal tubule & collecting ducts – little permeability to Na+, Cl+ & Urea

Ascending limb & 1st part of distal tubule – actively transport NaCl (& impermeable to water, thus water & solute are separated)

Quick Summary

The counter current arrangement multiplies a small transepithelial gradient (200 mOsm/kg) into a large longitudinal gradient (1200 mOsm/Kg)

Urea

The osmotic pressure of inner medulla is 1200-1400 mOsm/kg

Half attributable to NaCl

Another half to urea

Urea

Small solute

Freely filtered in glomerulus

Passively reabsorbed in proximal tubule

At hairpin end urea concentration is 200mOsm/kg due to passive secretion

Urea is concentrated in medulla

Thick asc limb: Na + Cl removed from tubular fluid

Tubular fluid is hypotonic compared to plasma

When urine concentrated due to ADH, urine osm reach 290 mOsm/kg, similar to plasma. DIFFERENCE is osm due to urea (NaCl removed)

Urea

As tubular fluid flows into medulla, more water is reabsorbed due to ADH.

Urea concentration in urine rises until it exceeds interstitium

Urea is concentrated by removal of water

Urea

When urea concentration is high, it moves from tubule into interstitium

There is conservation of urea (recycled)

Urea can be excreted in large amounts without losing large amounts of water

Vasa Recta

Provides blood flow to medulla

Does not alter the gradient

Removes ions & water that have been reabsorbed

Vasa Recta

Derived from efferent arteriole of juxtamedullary glomeruli

Walls are permeable to salt & water

When blood reaches deepest end of medulla, contents have equilibriated

Vasa Recta

Same occurs on the way up to cortex (equilibrium between blood & interstitium)

Blood leaving vasa recta slightly hyperosmotic than plasma

Countercurrent arrangement & low blood flow maintains gradient

ADH

Regulates absorption of water from collecting ducts

Secreted by posterior pituitary in response to increased plasma osmolality

Secretion regulated by osmoreceptors in hypothalamus

ADH

10-15% filtered water is reabsorbed under influence of ADH

Remainder has been reabsorbed along the nephron

If posterior pituitary is unable to secrete ADH – large volumes of urine / polyuria (diabetes insipidus)

ADH

ADH inserts water channels into the cells of the collecting ducts

Vasopressin (ADH) increases water permeability by binding to V2 receptors in the basolateral membrane of cells in the collecting ducts, stimulated adenyl cyclase to produce c’AMP, which then activates protein kinase A that leads to insertion of aquaporin-2 (AQP2) water channels into the apical membrane

AQP1 - found across the ascending limb of the loop of Henle. Not sensitive to vasopressin

AQP2 - found on the apical surface of the collecting duct. Sensitive to vasopressin

AQP3 - found on the basolateral membrane of the cortical and outer medullary collecting duct

AQP4 - found on the basolateral membrane of the inner medullary collecting duct.

The End

What is the diagnosis of the case history?

Thank you

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