Mechanisms to Adjust Urine Concentration Flashcards
“fine tuning” of water and salt content
- where?
- how?
In late distal collecting tubule, collecting duct
Aldosterone => Na reabsorption, K excretion, H excretion
ANP => inhibits Na reabsorption, increases Na excretion
ADH => stimulates water reabsorption (insert AQPs), increase action of Na/K/2Cl cotransporter, increases reabsorption of urea
Cation transport in Late DT and CD
large negative transepithelial potential
Na moves into cell due to concentration gradient created by NaK ATPase
K move into lumen due to large negative potential
Aldosterone in Principal Cells
increases Na reabsorption
- incorporation of Na channels into luminal membrane
- Incorporation of Na/K ATPase ion pump in basolateral membrane
Physiologic control of permeability in collecting duct in a well hydrated person
collecting duct is impermeable to water
secrete dilute urine in large amounts
Physiologic control of permeability in collecting duct in a dehydrated person
collecting duct is VERY permeable to water
small volume of very concentrated urine is excreted
How does ADH alter water reabsorption?
ADH binds to V2 receptors causing a phosphorlyation reaction with cAMP and PKA leading to protien phosphorylation which allows AQP2 to be inserted in luminal membrane and INCREASE reabsorption of water
ADH release increased with:
volume depletion
increase in osmolarity
ANGII release
What is the concentration of solutes and blood flow in inner medulla?
Why is this important?
High solute concentration
Low blood flow
low blood flow important for concentrating urine because you have established a concentration gradient that allows water to be reabsorped (ie concentrate urine) and a high blood flow would wash this gradient out
Counter Current Multiplier Mechanism
- Function
Allows kidneys to excrete highly concentrated urine
Conserves water in dehydration
Components of Counter current multiplier mechanism
- Descending/Ascending Loop of Henle
- Vasa recta capillaries
- Collecting ducts
Mechanism of Action of Counter Current Multiplier
- Na+ gradient that the Na/K/2Cl cotransporter can establish in TAL is 200 mOsm/Kg
- Interstitium becomes hyperosmolar and pulls water out of the descending limb
- Urine is descending limb is concentrated
- Process repeats
- Augmented by action of ADH in CD
- urea reabsorption form inner medullary collecting ducts into interstitium
- urea contributes to 50% of the osmolarity
Role of Urea in Counter Current Multiplier Mechanism
with ADH secretion collecting tubule is permeable to water (via AQP2) => water leaves => higher concentration of urea in collecting tubule => increase gradient => urea passively diffuses into interstitium => establishes higher gradient at LOOP OF HENLE aids in concentrating urine there. (urea about 50% of osmolarity of interstitium)
Describe urea recycling
PCT = urea reabsorbed DLOH = about 50% of filtered urea remains ALOH = 100% of urea
This is because urea is reabsorbed by collecting duct to create concentration gradient then secreted back into lumen of loop of henle so it can be recycled and used again to create this gradient
What would happen regarding urea in case of excess ECF volume?
- No ADH
- increased RBF
- increased GFR
- Decreased urea recycling (lower concentration since more H2O present)
- Urea excretion
- Less concentrated urine
Vasa Recta role in counter current multiplier system
Descending vasa recta with ascending LOH reabsorbs Na
Ascending vasa recta with descending LOH absorbs water
vasa recta flows the opposite direction of urine
Osmotic Diuretics
work in PCT
decrease water reabsorption by increasing osmotic pressure of tubular fluid
Loop Diuretics
work in TAL of loop of henle
decrease activity of Na/K/2Cl cotransporters and reabsorption in teh thick ascending loop of henle
- disruption of countercurrent multiplier system
- increase delivery of soutes to distal nephron segment which acts as osmotic agent to decrease water reabsorption
Thiazide Diuretics
decreases NaCl reabsorption in the early distal tubule
What happens to K balance with diuretics?
Increase RBF leading to K secretion and K imbalance
- Loop diuretics often given with K sparing diuretics
Carbonic Anhydrase Inhibitors
block sodium bicarbonate reabsorption at PCT
- dec Na and HCO3 reabbsorption causes diuresis
- can cause acidosis due to loss of HCO3
Competitive Inhibitors of Aldosterone
decrease Na reabsorption from and decrease K secretion into cortical collecting tubule
-Na = osmotic diuretic can increase ECF K levels ( K sparing diuretic)
Sodium Channel blockers
stop Na entery into Na channels in luminal membrane
dec Na reabsorption
dec K secretion
Antidiuresis
conservation of water and excretion of concentrated urine
Osmoreceptor-ADH feedback system
increased ECF osmolarity leads to shrinking of osmoreceptor cells in hypothalmus leading to ADH secretion
Aortic arch and carotid sinus baroreceptors
decrease in arterial pressure leads to ADH secretion
Cardiac atria
decreased blood volume leads to ADH secretion
What leads to ADH secretion and senses that?
- Inc ECF osmolarity (osmoreceptors in hypothalamus)
- Dec arterial pressure (aortic arch and carotid sinus baroreceptors)
- Dec blood volume (cardiac atria)
What other stimuli is associated with ADH secretion?
Thirst (+ANGII)
Solute concentration of vasa recta when you enter and leave?
osmolarity higher when you leave tubule
solute concentration of loop of henle when enter vs leave
osmolarity lower when you leave loop of henle
Ingest 1L pure water what happens?
increase urine flow in about 1 hour
decrease urine concentration
can excrete more pure water without changing the amount of solutes excreted
Low ADH
high volume of dilute urine excreted
CD impermeable to water
lower solute concentration in medullary insterstitium
Obligatory Urine volume
70kg person = 600 mOsm/day waste, max urine concentration = 1200 mOsm/L
600mOs/day X1L/1200mOsm = 0.5 L/day
Osmolar Clearance
The process of concentrating or diluting the urine requires the kidneys to excrete water and solutes somewhat indpedently
Osmolar clearance equation
Cosm = Uosm x V/Posm
What happens to Cosm when kidneys
- excrete excess solute?
- retain solute?
- increases Cosm
- decreases Cosm
Free water Clearance
the excretion of water in excess of the amounts needed to excrete isosmotic urine (the excretion of solute-free water by the kidneys)
Free water clearance equation
Ch2o= V- Cosm (v = urinary flow rate)
Uosm< Posm
Ch2o is postive
pure water is cleared from the body
Uosm > Posm
Ch20 is negative
pure water is retained
Affect of ADH on Ch20
reabsorb more water leads to decreased free water clearance
Fractional Excretion
the fraction (percentage) of filtered load of a substance that is excreted in urine
Fractional excretion equation
Fex = (UxV)/(PxGFR)
Fraction excretion equation for Creatine clearance
Fex= (UxPcr)/(PxUcr)
Disorders of Urinary concentrating ability
- Inappropriate secretion of ADH (Central DI/SIADH)
- Impariment of countercurrent mechanism
- Inability of kidney to react to ADH (Nephrogenic DI)
Central Diabetes Inspidus
Failure to produce ADH
SIADH
continous ADH production
Nephrogenic Diabetes Insipidus
kidney can’t react to ADH
How do the following affect osmolarity?
- increase RBF
- increase GFR
- Absence of ADH
- increase flow in vasa recta and washes gradient, can’t concentrate urine
- inc tublar flow, can’t get enough Na out, urea not as concentrated due to water, DEC MEDULLARY HYPERSOMOLARITY
- reduce water reabsorption, reduced urea reabsorption, less conentrated urine
