L5 Urinary Concentration And Dilution Flashcards
When body fluids are hyposmotic (water excess), the kidneys excrete a ________ urine.
Dilute urine (as low as 50 mOsm/L - water diuresis)
When body fluids are hyperosmotic (water deficit), the kidneys excrete a ________ urine.
Concentrated urine (up to 1200 mOsm/L - antidiuresis)
The kidneys can regulate water excretion independently of ….
Solute excretion
_________________ creates a large gradient in the interstitial fluid from the corticomedullary border to to teh tip of the papilla by multiplying a small local gradient created by the epithelium of the loop of Henle.
The Counter-Current Multiplier
In the Loop of Henle, reabsorption of _____ exceeds reabsorption of water, which is key for establishing…
Na+
Key for establishing the concentration gradient of sodium in the renal medulla.
At any given level in the loop of Henle, the osmotic concentration of the fluid in the descending limb ______ the osmotic concentration of the interstitial fluid.
Equals
The descending limb has no active transport of ions but is very permeable to water, so the fluid in the descending limb is in osmotic equilibrium with the ISF.
Because the thick ascending limb of the loop of Henle actively absorbs ions but is impermeable to water, the osmotic concentration of the urine passing through it is ________ than the osmotic concentration of the ISF
Less - the urine becomes more dilute as it passes through the thick ascending limb and ions are reabsorbed into the ISF.
Fluid is progressively ________ as it flows down the descending limb and progressively _______ as it flows up the ascending limb
Concentrated, then diluted
_______ is the largest osmotic gradient that can be maintained across the wall of the ascending limb.
200 mOsm
Beyond 200 mOsm, back diffusion will equal the rate of reabsorption
The countercurrent multiplier is a multiplier because…
The 200mOsm/L created by active transport has been multiplied (to 1200 mOsm/L)
The countercurrrent multiplier is countercurrent because…
The flow is in opposing directions through the two limbs
What is the essential component that allows the countercurrent multiplier to exist?
Active transport (particularly of Na+)
Active transport of sodium in the thick ascending limb of the loop of Henle is primarily via…
The Na+/K+/2Cl- cotransporter (NKCC2)
Moves a molecule of sodium, a molecule of potassium, and two molecules of chloride all at once with one turn of the mechanism.
NKCC2 transporter is stimulated by ____ and blocked by ____.
Stimulated by ADH, blocked by furosemide (Lasix)
MOA for loop diuretics
Inhibit ionic transport in the thick ascending limb of the loop of Henle by blocking the action of the NKCC2 transporter (moves 1Na, 1K, and 2Cl all at once)
Vasa recta are not multipliers but the are ___________.
Countercurrent exchangers
As blood flows down the capillary, NaCl diffuses in and H2O out.
As blood flows up the capillary, the reverse occur
This serves to protect the ISF gradient, and is an entirely passive process.
Urea is generated by
Hepatic protein catabolism
Why is urea important?
It contributes to hyperosmotic renal ISF and to the concentration of the urine
Urea is recycled in the:
Medulla of the kidney
Permeability to urea of the inner medullary portion of the collecting duct is controlled by ADH
Why can’t people on low protein diets concentrate urine as well?
Low protein diet —> reduced urea formation from catabolism in the liver
The reduced urea makes it difficult to create the proper hyperosmotic renal ISF that allows for the concentration of urine.
Describe NaCl transport in the early distal convoluted tubule
The NKCC2 transporter is NOT present in teh early DCT, but there is a NaCl transporter (NCC) in the luminal membrane.
The early portion of the DCT is not permeable to water (continues to dilute tubular fluid)
The NCC transporter is the target of thiazide diuretics.
The early distal tubule is also referred to as the ________ segment
Diluting segment
Because it is not permeable to water and thus continues to dilute the tubular fluid as ions are transported out via the NCC transporter.
The late distal tubule and collecting duct are composed of what two types of cell?
Principal cells
• Reabsorbed Na+ and secrete K+
• Site of ALDOSTERONE and ADH action
Intercalated cells (type A)
• Secretes H+
• Reabsorbed K+
Na+ reabsorption and K+ secretion in the late distal tubule and collecting duct depend on …
The Na/K ATPase in the basolateral membrane and the apical channels for both ions
Describe the effects of aldosterone on the late Distal tubule and collecting duct
Principal cells of the DCT reabsorb Na in exchange for K.
Aldosterone increases the number of apical Na and K channels (ENaC - Epithelial Na+ channel), and increases Na/K ATPase activity, thereby increasing the reabsorption of Na+.
(Also has a small effect on H/K ATPase in the alpha-Intercalated cells - important for K+ reabsorption and acid/base balance)
What is the target for the diuretic Amiloride?
The ENaC (epithelial Na+ channels), which allow for the reabsorption of Na by the distal tubule and collecting duct.
Aldosterone enhances reabsorption of Na but Amiloride inhibits it.
Why would you see an increase in aldosterone in cases of hypokalemia?
While aldosterone mostly effects the principal cells to reabsorb Na, it also effects the intercalated cells by enhancing the activity of the H/K-ATPase, allowing for the reabsorption of potassium (K)
Water and urea permeability of the collecting duct is controlled by:
Vasopressin (aka - ADH)
Water permeability can be high or low:
• Dependent on water channels (aquaporins) in the apical membranes of the CD cells
• ADH causes the insertion of aquaporins in to the apical membranes…
MOA of vasopressin (ADH)
On binding with its receptor sites on the basolateral membrane of a distal tubule or collecting duct cell, ADH activates the cycle AMP second messenger system within the cell.
Cyclic AMP in turn increases the opposite luminal membrane’s permeability to H2O by increasing the number of aquaporins in the membrane.
The increased permeability to H2O in DCT and CD allows for more reabsorption of water (and therefore more concentrated urine)
60-80% of NaCl and water are reabsorbed in the ______.
Proximal tubule.
The tubular fluid remains isosmotic.
Water is reabsorbed in the _______________
Descending limb of the loop of Henle
Fluid becomes hyperosmotic.
NaCl is reabsorbed in the ____________.
Ascending limb of the LOH.
Fluid becomes slightly hyposmotic
No water reabsorption normally occurs in the ___________.
Early distal tubule, even though there is some NaCl reabsorption.
Fluid remains hyposmotic
What hormonal actions occur in the late distal tubule and collecting duct?
Na+ reabsorption is regulated by aldosterone levels
(+) ADH: water reabsorption is high, urine becomes hyperosmotic (as high as 1200 mOsm/L, same as osmolality of surrounding ISF)
(-) ADH: water reabsorption is inhibited —> dilute hyposmotic urine is produced
