Is plasma ADH high or low in patients with central diabetes insipidus?
ADH is low – the posterior pituitary cannot produce it.
How does aldosterone increase sodium retention and potassium excretion?
It increases the presentation of ENaC channels in the collecting duct. This increases the reabsorption of sodium, and causes a concomitant ejection of potassium.
What is a medullary washout?
The event in which increased blood flow through the vasa recta dissipates the medullary gradient by literally washing out the solute.
What would diabetes insipidus do to plasma sodium levels?
Diabetes insipidus increases plasma sodium levels
(Diabetes insipidus = hypernatremia)
What two general mechanisms can be the cause of symptoms in nephrogenic diabetes insipidus?
Either a direct failure of the distal and collecting tubules to response to ADH,
or a failure of the countercurrent multiplier to establish a hyperosmotic medullary interstitium.
What is the osmolality of the tubular fluid entering the descending limb of the loop of Henle?
What four things (discussed along with polyuria) can increase the output of solutes in the collecting duct?
Diuretics, diabetes mellitus, hyperthyroidism, and hyperparathyroidism.
What is normal urine output?
1 to 2 L/day
What are the general functions of the intercalated cells?
Reabsorption of potassium.
Secretion of hydrogen.
What is obligatory urine volume?
How do we calculate it?
Obligatory urine volume is the minimum amount of urine that would have to be produced to secrete the minimal amount of solutes that must be excreted.
Take the minimum amount of solute (about 600 mOsm per day) and divide by 1200 mOsm per liter, the maximum concentration of urine.
(.5 L/day for a normal 70 kg human)
Interstitial fluid in the medulla is always at osmotic equilibrium with what portion of the nephron?
The descending limb of the loop of Henle.
(The medullary interstitial fluid and the descending loop of Henle will always have the same osmolality as they descend further into the medulla.)
What will the osmolality of the intratubular fluid of the distal tubule be in the presence of ADH?
Maximum of 300 mOsm / kg H20
(recall that the interstitial fluid of the cortex is isotonic)
In a patient with hypernatremia due to diabetes insipidus, what would we expect the osmolality of their urine to be?
Even though hypernatremia should increase the ability of the body to reabsorb water from the collecting ducts, the inability of the collecting ducts to respond to ADH makes this irrelevant.
What urea transporters are responsible for urea exit from the inner medullary collecting duct?
UT-A1 / UT-A3
What ADH related disease is a major cause of low sodium levels?
Where does almost all of the urea leave the nephron?
The inner medullary collecting duct.
What portion of the collecting duct is always impermeable to water?
The cortical portion is always impermeable to water.
What is considered oliguria?
300 to 500 mL/day
When osmoreceptors are triggered, which pathway is triggered first: the ADH pathway, or the thirst pathway?
The ADH pathway is generally triggered first.
What are the general functions of the principal cells?
Reabsorption of sodium, chloride, and water.
Secretion of potassium
What urea transporter is responsible for urea uptake into the thin descending loop of Henle?
What is the function of desmopressin?
Desmopressin directly acts on V2 receptors to increase reabsorption of water in the distal tubular segments.
What is the maximum osmolality of the interstitium of the medulla of the kidney?
1200 to 1400 mOsm / kg H2O
What are the four mechanisms that can cause polyuria?
Increase water intake.
Increased solute excretion.
Inability of the kidney to reabsorb water in the distal convoluted tubule.
What can be determined by a U(osm)/P(osm) of greater than one, and less than one?
U(osm)/P(osm) of greater than one: kidneys are able to produce concentrated urine.
U(osm)/P(osm) of less than one: kidneys are able to produce dilute urine.
When there is excess water in the body, what happens to the reabsorption of urea into the medullary interstitium?
Urea reabsorption into the medullary interstitium is reduced.
(There is a reduced concentration of urea and the inner medullary collecting ducts, therefore there is less urea to reabsorb)
How is potassium secreted by the principal cells?
Potassium is up taken by the cell by the action of the Na/K ATPase, and then transported out of the cell down its concentration gradient.
How can we clinically diagnose between central and nephrogenic diabetes insipidus?
Administer desmopressin. If urinary output quickly returns to normal, the patient has central diabetes insipidus. If it does not, nephrogenic diabetes insipidus is more likely.
What would happen in the event of decreased blood flow through the vasa recta?
The net effect is that salt and solute transport out of the tubules of the nephron is decreased because there is less oxygen to the solute transporters of the nephron.
This results in the diminished ability to concentrate urine.
What is considered anuria?
What range is considered polyuria?
At any point along the length of the thick ascending loop of Henle, what is the difference between the osmolality of the tubular fluid, and the fluid of the interstitium?
200 mOsm / kg H2O
What is considered polydipsia?
Water intake >100 mL/kg/day (6 L/day)
What chemical mechanism directly causes release of ADH from the supraoptic and paraventricular nuclei?
Nerve stimuli causes an increase in membrane permeability to calcium – and concomitant increase in intracellular calcium. This causes ADH release.
What three things (discussed along with polyuria) can increase GFR?
Fever, hyperthyroidism, hyper metabolic states
What is the equation for free water clearance?
Free water clearance = urine flow rate - osmolar clearance
Osmolar clearance is calculated the same way we would calculate any other type of clearance. C(osm) = [U (osm) x V]/P (osm)
What medications can cause nephrogenic diabetes insipidus?
Diuretics, lithium (antipsychotic), and tetracyclines.
What is the function of the vasa recta?
Remove the water and the solute that is constantly added to the medullary interstitium.
Supply oxygen to the cells of the nephron.
Maintain the medullary interstitial gradient.
The tubular fluid of the collecting ducts – is it hypotonic or hypertonic when under the effect of ADH?
What about in the absence of ADH?
ADH causes water resorption, and so the inter-tubular fluid is hypertonic
In the absence of ADH, the intertubular fluid is around 100 mOsm / kg H2O (hypotonic)
How does the ascending loop of Henle maintain a 200 milliosmolar gradient between itself and the interstitial fluid?
Active sodium chloride channels, such as the Na+/K+/2Cl- transporter.