Changes In Plasma Osmolarity Flashcards
How much do we urinate a day?
1-1.5L/day
If water intake is less than water excretion, what happens to the osmolarity?
Osmolarity increases
What is urinary osmolarity?
500-700mOsm/L
What senses changes in plasma osmolarity?
Hypothalamic osmoreceptors in the OVLT
What are the two efferent pathways for regulation of osmolarity? What is the effector and what is changed?
ADH - effector is kidney, affects renal water excretion
Thirst - effector is brain and drinking behaviour, water intake is affected
How are changes in osmolarity detected?
Fenestrated leaky endothelium exposed directly to systemic circulation
Senses changes in plasma osmolarity - osmoreceptors expand when more dilute and shrink with higher osmolarity
Responses mediated by the two efferent pathways
Where is ADH released from?
Posterior pituitary
How is the ADH pathway initiated?
When osmolarity increases, osmoreceptors shrink
Stimulate secretion of ADH
More water is retained
Decreased osmolarity inhibits ADH secretion
What is ADH?
A small peptide - about 8 amino acids long
Hormone
What does ADH do?
Addition of aquaporin 2 in the apical membrane of the collecting duct.
Increased reabsorption of water
Increases permeability of collecting duct to urea causing its reabsorption, which water also follows
How is aquaporin 2 removed from the membrane?
Endocytosis
What aquaporin does the basolateral membrane always contain and why?
Aquaporins 3 and 4
So that it is constantly permeable to water
Any water that enters across the apical membrane can pass into the peritubular blood
Why does increased urea reabsorption in the collecting duct increase water reabsorption?
Water follows it out
Urea also moves down its conc gradient into the ascending limb which is permeable to urea but not water
Can then pass back into the CD where it is reabsorbed in the medullary portion and recycled again
Where is ADH secreted from?
Posterior pituitary
What is secretion of inappropriate ADH (SIADH)?
Excessive release of ADH from posterior pituitary gland or other source
What happens in SIADH?
Dilution all hyponatraemia in which plasma sodium levels are lowered and total body fluid increases
Symptoms of SIADH?
Nausea Vomiting Headache Confusion Lethargy Fatigue Appetite loss Restlessness Irritability Muscle weakness Spasms Cramps Seizures Decreased consciousness Coma
How is SIADH treated?
ADH antagonists
What is diabetes insipidus?
When the posterior pituitary gland doesn’t produce enough ADH or acquired insensitivity of kidney to ADH
Water is inadequately reabsorbed from CD and lots of urine is produced
How is diabetes insipidus treated?
ADH injections
ADH nasal spray
What happens to the osmolarity of the kidney as you descend deeper into it?
It increases
How is the medullary gradient generated?
Active NaCl transport in thick ascending limb and recycling of urea sets up the osmotic gradient
How does the thick ascending limb have a diluting effect on the ultrafiltrate?
Removes solute/ions without water following
What happens to the medullary gradient when loop diuretics are used?
Blocks NaKCC transporters
Medullary interstitium becomes isotonic
Large amounts of dilute urine are produced
What maintains the osmotic gradient of the medulla?
Flow in the vasa recta in the opposite direction to the tubule
(Vasa recta acts as a countercurrent exchanger, conc gradient produced by LoH acts as a counter current multiplier)
What happens to the blood as it passes through the vasa recta?
Begins as isosmotic
Enters hyper osmotic tissue of medulla
Na and Cl diffuse into the vasa recta
Osmolarity of blood increases
At tip of loop it is isosmotic with medullary interstitium
Blood ascending towards cortex is now hyper osmotic compared to interstitium
Water moves in from descending limb of loop of Henle
So what is the overall effect of the vasa recta?
Prevent the medullary hyper osmolarity from being dissipated
What happens to ADH and urine osmolarity of plasma osmolarity decreases?
No ADH stimulation No aquaporin in later DCT and CD Less water reabsorption Tubular fluid with lots of H2O passes through Urine is hypo-osmotic
What happens to ADH and urine osmolarity of plasma osmolarity increases?
ADH is released so aquaporin channels are inserted onto the apical membrane
Cell becomes more permeable to water
More hyperosmotic urine
How does ADH cause insertion of aquaporin 2 on the apical membrane?
Binds to GPCR on the basolateral membrane
ATP -> cAMP
PKA produced
Aquaporin 2 produced
So what are the overall effects of ADH?
Vasoconstriction
Increases Na, K, Cl reabsorption in ascending limb
Increases water reabsorption in late DT and CD
Increases K+ secretion in cortical CD
Increases urea reabsorption in CD
