2008 urine concentrating mechanism
TRANSCRIPT
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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