SM 197a - Water Balance Flashcards
What are the requirements for excreting concentrated urine?
- Signal
- Hypothalmic osmoreceptors sense high serum Na+
- -> ADH release
- Favorable concentration gradient
- So that there is a driving force for water reabsorption in the collecting duct
- Functional receptors for the signal
- V2 vasopressin receptors on the basolateral membrane of collecting duct cells
- Functional response to receptor/ligand binding
- Increase adenylyl cyclase activity
- -> Increased cAMP
- -> Insertion of AQP-2 into the membranes of collecting duct cells
Which section of the kidney tubule reabsorbs the most water?
Proximal tubule
Aquaporins (AQP1) is constituitively inserted into the proximal tubular epithelial cells; water is always reabsorbed here
What signal drives the release of ADH from the pituitary?
Increased osmolality = primary driver of ADH release
- In addition, volume depletion sensitizes the pituitary to respond to volume depletion
- As volume begins to deplete, the pituitary begins to respond to low volume
- As volume depletion worsens, the pituitary becomes conditioned to release more ADH
- Nausea can also induce ADH release
(No sensitization required)
Which sections of the kidney tubule are under control of ADH?
Cortical collecting duct
Medullary collecting duct
What is the “prototype” osmotic diuretic?
Mannitol
Which of the following nephron segments has the lowest water permeability under any circumstance?
a. Proximal tubule
b. Descending limb of the loop of Henle
c. Ascending limb of the loop of Henle
d. Cortical collecting duct
e. Inner medullary collecting duct
c. Ascending limb of the loop of Henle
What is counter-current exchange?
How does it contribute to kidney function?
The peritubular capillaries (vasa recta) flow antiparallel to the loop of Henle. They remove water to keep the osmotic gradient intact
- Blood coming into the medulla will absorb solute and lose water
- This water, plus water from the thin descending loop of Henle will be reabsorbed as the capillary exits the medulla
- More water is absorbed than solute - the vasa recta helps to maintain the high osmolality of the medulla by removing the water that is reabsorbed
- This helps to maintain the kidney’s ability to concentrate urine
Describe the mechanism of action of vasopressin
- Vasopressin (ADH) is released from the posterior pituitary in response to increased plamsa osmolality
- Or volume depletion or nausea
- ADH binds to its V2R receptor on the basolateral side of collecting duct cells
- Stimulates adenylyl cyclase
- Increased intracellular cAMP
- Insertion of AQP2 into the luminal membrane
In the genetic form of nephrogenic diabetes insipidus, loss-of-function mutations in the vasopressin V2 receptor impair the response of the collecting duct to antidiuretic hormone (ADH).
What is the likely consequence of this impairment at the cellular level?
- Aquaporin-1 water channels are not inserted into the plasma membrane
- The V2 receptor causes excessive activation of adenylyl cyclase
- Water permeability of collecting duct membranes remains low even in the presence of high circulating levels of ADH
- Aquaporin-2 water channels are mis-localized to the basolateral membranes
c. Water permeability of collecting duct membranes remains low even in the presence of high circulating levels of ADH
What are the requirements for excreting dilute urine?
- Signal
- Hypothalmic osmoreceptors sense low serum Na+
- Adequate delivery of NaCl to the thick ascending limb
- To prevent upregulationof Na+ reabsorption, which would increase osmolality (increase Na+) and signal for ADH release
- Functional thick ascending limb
- To remove solutes from the urine
Key: you are not adding water to the urine, you are removing salt and preventing water from following
(no ADH = no water reabsorption in collecting duct, even if the urine is less concentrated than the interstitium)
How does K+ secretion change if Na+ reabsorption in the cortical collecting duct is inhibited?
In the cortical collecting duct:
Decreased Na+ reabsorption -> Decreased K+ secretion
Ex: K+ sparing diuretics (amiloride)
(Na+ reabsorption -> negatively charged lumen -> K+ secretion_
A 23 year female suffers a head injury in a motorcycle accident. Several days later, she notes polyuria and intense thirst. Her urine appears extremely clear (“like water”) and she has to drink more than 5 liters of water per day to satisfy her thirst. Medical evaluation revealed a urine osmolality of 90 msom/l and a serum vasopressin level of < 1 pg/ml (undetectable). A diagnosis of acquired central diabetes insipidus was made. Interestingly, despite the near absence of vasopressin and excretion of large volumes of dilute urine, her serum sodium concentration was only mildly elevated (147 mEq/L; normal range 135-145 mEq/L) as was her serum osmolality (296 mosm/l; normal range 280-290 mosm/l). Why doesn’t she have a more severe degree of hypernatremia and hyperosmolality?
- Although vasopressin levels are low, females have circulating oxytocin that can promote water reabsorption.
- She has maintained a low dietary sodium intake.
- Her thirst mechanisms are intact and she has been drinking water.
- She has normal sodium balance and this is maintaining her serum sodium concentration near the normal range.
- The laboratory tests must be wrong.
c. Her thirst mechanisms are intact and she has been drinking water.
What is the difference between central and nephrogenic diabetes insipidus?
Diabetes insipidus = problem with ADH signaling
Both cause persistent thirst, water consumption and frequent urination -> Susceptibility to de-hydrateion and electrolyte imbalance
-
Central
- Cannot synthesize ADH
-
Nephrogenic
- Kidney is resistant to ADH
- Causes
- Mutations in V2R gene (X-linked)
- Mutations in AQP2 (Autosomal)
- Li+ used as a treatment for bioplar disorder (Acquired)
What is diabetes insipidus?
Diabetes insipidus = ADH signaling is not working
May be central or nephrogenic
- Central
- Problem synthesizing ADH in the hypothalmus
- Nephrogenic
- Problem responding to ADH in the kidney
What are the mechanisms of medullary hyperosmolality?
-
Countercurrent mulitplier
- Established by Na+ reabsorption in the thick ascending limb
- Establishes the initial osmotic gradient
-
Urea cycling
- Strengthens the osmotic gradient
-
Countercurrent exchange
- The vasa recta (blood vessel) flows in the opposite direction of the kidney tubule. Water reabsorbed by the thin descending limb goes here
- Maintains the osmotic gradient
Which parts of the kidney tubule are permeable to urea?
Medullary collecting duct
- Urea that is reabsorbed in the medullary collecting duct contributes to the osmolarity of the inner medulla. This strengthens the gradient for water reabsorption in the thin descending limb and the collecting duct
True or false: Hypernatremia indicates excess sodium in the body
False
Hypernatremia indicates an imablance between salt and water
Usually a result of dehydrateion (not enough water in the body)
What factors promote cell uptake of K+?
(More K+ in the cell, less in the serum)
- Na+/K+ ATPase activity
- Insulin
- Catecholamines (b2 adrenergic receptors)
- Alkalosis
What physiological states trigger ADH release?
- Increased plasma osmolality (main driver)
- Volume depletion
- Nausea
Where is ADH synthesiszed?
From where is it released?
Synthesized in the hypothalmus
Released from the posterior pituitary
What factors promote cellular efflux of K+?
(More K+ in the serum, less in the cell)
- Exercise
- Extracellular fluid hyperosmolality
- Cell breakdown
- Acidosis
Which section of the kidney tubule is responsible for establishing the countercurrent multiplier?
Thick (and thin) ascending loop of Henle
- NaCl is pumped out of the lumen and into the intersititum via active transport
- This establishes an osmotic gradient between the water-permeable thin descending limb and the interstitial space
- Water is pulled into the interstitial space and carried away by the vasa recta
- As this fluid flows up the thin and thick ascending limbs, salt is pumped out (see 1st bullet point)
How does K+ secretion change if Na+ reabsorption in the cortical collecting duct is increased?
In the cortical collecting duct:
If Na+ reabsorption is increased, K+ secretion is increased
(Na+ reabsorption -> negatively charged lumen -> K+ secretion)
Which sections of the kidney tubule are impermeable to water?
Ascending limb
Distal convoluted tubule
Reabsorption of solutes in these sections dilutes the urine.
- Presence of ADH =>
- Water will be absorbed in the collecting tubule, and excreted urine will be concentraed
- Absence of ADH =>
- Water will not be absorbed in the collecting tubule, and dilute urine will be excreted
What is an osmotic diuretic?
A diuretic (ex: mannitol, glucose) that remains in the lumen of the kidney. Its presence increases the osmolarity of the filtrate, which prevents water and solute reabsorption
(There is no driving force for any exchange of water or solute if the filtrate has such a high osmolality?)
Which section of the kidney tubule is responsible for K+ secretion?
Cortical collecting duct
(principal cells)
What are the driving forces for K+ secretion from the cortical collecting duct?
- High intracellular potassium
- Increased Na+ reabsorption
- -> Negatively charged fluid in the tubular lumen
Potassium secretion by the collecting duct is affected by all of the following factors EXCEPT:
- lumen-negative transepithelial voltage in the collecting duct
- aldosterone stimulated sodium reabsorption by principal cells in the cortical collecting duct
- tubular fluid flow rate in the collecting duct
- concentration of bicarbonate in collecting duct tubular fluid
- vasopressin stimulated water reabsorption in collecting duct
E. vasopressin stimulated water reabsorption in collecting duct
