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131 Cards in this Set

  • Front
  • Back
What are the three hormones that the kidneys synthesize and secrete?
Renin
Erythropoietin
1,25-dihydroxycholecalciferol
What is the difference between superficial cortical nephrons and juxtamedullary nephrons?
The two types of nephrons are distinguished by the location of their glomeruli. The superficial cortical nephrons have their glomeruli in the outer cortex, have relatively short loops of Henle, and descend only into the outer medulla. Juxtamedullary nephrons have their glomeruli near the corticomedullary border. The glomeruli are also larger, have higher glomerular filtration rates, have longer loops of Henle that descend deep into the inner medulla and papilla, and are essential for the concentration of urine.

The vasa recta are found following the juxtamedullary nephrons.
What does the renal artery branch into?
Interlobar arteries
Arcuate arteries
Cortical radial arteries
Who has the highest percentage of water? Who has the lowest percentage of water?
Thin men have the highest percentage of body weight as water (~70%).
Obese women have the lowest percentage of body weight as water (~50%).
How much water is in the ICF? In the ECF?
About two-thirds of total body water is in the ICF. About one-third is in the ECF.
What is the 60-40-20 rule?
60% of body weight is water, 40% is ICF, 20% is ECF.
How much of the ECF water is found in the interstitial fluid? In the plasma?
About three-fourths of the ECF is found in the interstitial compartment, and the remaining one-fourth is found in the plasma.
How much of the blood is plasma?
On a volume basis, plasma constitutes 55% of blood volume, and blood cells constitute the remaining 45% of blood volume.
What is the average hematocrit? Is it higher in males or in females?
The average hematocrit is 0.45 or 45%. It is higher in males (0.48) than in females (0.42).
What is the Gibbs-Donnan effect?
The Gibbs-Donnan effect predicts that plasma will have a slightly higher concentration of small cations than interstitial fluid and a slightly lower concentration of small anions.
What is special about mannitol? Where is it distributed?
Mannitol is a large molecular weight sugar that cannot cross cell membranes. It will be distributed in ECF but not ICF.
Mannitol is a marker for ECF volume.
What substances are distributed wherever water is found?
The markers for total body water include isotopic water (D2O and tritiated water) and antipyrine.
What are some markers for plasma volume?
Substances that distribute in plasma but not in interstitial fluid, because they are too large to cross capillary walls. These substances include radioactive albumin and Evans blue (dye that binds to albumin).
How do you calculate ICF volume? Interstitial fluid volume?
Since there are no unique markers, ICF volume is calculated as the difference between total body water and ECF volume. Interstitial fluid volume is the difference between ECF volume and plasma volume.
What is the ECF volume determined by?
The volume of a body fluid compartment depends on the amount of solute it contains. Since the major cation of ECF is Na+ (with accompanying anions Cl- and HCO3-), ECF volume is determined by the amount of NaCl and NaHCO3 (sodium bicarbonate) it contains.
What is the normal value for osmolarity of the body fluids?
290 mOsm/L (~300 mOsm/L for simplicity)
What is the equation to estimate plasma osmolarity?
Plasma Osmolarity (mOsm/L) =

2 x Plasma Na + Glucose/18 + BUN/2.8
Why is the Na+ concentration multiplied by 2 in the equation?
Na+ must be balanced by an equal concentration of anions (Cl- and HCO3-).
What does volume contraction and volume expansion mean?
Volume contraction means a DECREASE in ECF volume.

Volume expansion means an INCREASE in ECF volume.
What does a hyperosmotic disturbance mean?
There has been an increase in ECF osmolarity.
What does a hyposmotic disturbance mean?
There has been a decrease in ECF osmolarity.
What are some examples of Isosmotic Volume Contraction?
Diarrhea, burn.
What are other consequences of diarrhea?
Increased hematocrit and increased plasma protein concentration, which are explained by the loss of isosmotic fluid from the ECF compartment.
What are some examples of Hyperosmotic Volume Contraction?
Sweating, fever, diabetes insipidus.
What occurs during water deprivation?
Hyperosmotic Volume Contraction:

Sweat is hyposmotic relative to ECF. Since a hyposmotic fluid is lost from ECF, ECF volume decreases and ECF osmolarity increases. The difference in osmolarity between ECF and ICF causes water to shift from ICF to ECF until the osmolarities are equal. In the new steady state, both ECF and ICF volumes will be decreased, and both osmolarities will be increased and equal to each other.
What happens to the plasma protein concentration and hematocrit during hyperosmotic volume contraction? Why?
Plasma protein concentration is increased, but the hematocrit is unchanged.

The hematocrit remains the same because even though ECF loses volume, the blood cells ALSO lose volume (ICF volume shift). The two effects offset each other.
What are some examples of Hyposmotic Volume Contraction?
Adrenal insufficiency
What occurs during adrenal insufficiency?
Hyposmotic Volume Contraction:

Adrenal insufficiency results in aldosterone deficiency, which leads to excess NaCl excretion in the urine. NaCl is an ECF solute, so ECF osmolarity decreases. This causes water to shift from ECF to ICF until both osmolarities are decreased and equal. In the new steady state, both ECF and ICF osmolarities will be lower than normal and equal to each other. ECF volume will be decreased and ICF volume will be increased.
What happens to the plasma protein concentration and hematocrit during hyposmotic volume contraction? Why?
Both plasma protein concentration and hematocrit will be increased because of the decrease in ECF volume. Hematocrit increases also because of the shift of water into red blood cells, increasing cell volume.
What are some examples of Isosmotic Volume Expansion?
Infusion of isotonic NaCl.
What occurs during an infusion of isotonic NaCl?
Isosmotic Volume Expansion:

Since NaCl is an extracellular solute, all of the isotonic NaCl solution is added to the ECF, causing an increase in ECF volume, but no change in ECF osmolarity. There will be no shift of water between ICF and ECF.
What happens to the plasma protein concentration and hematocrit during isosmotic volume expansion? Why?
Both plasma protein concentration and hematocrit will decrease (i.e., be diluted) because of the increase in ECF volume.
What are some examples of Hyperosmotic Volume Expansion?
High NaCl intake.
What occurs during high NaCl intake?
Hyperosmotic Volume Expansion:

After ingesting a lot of NaCl (i.e., eating a bag of potato chips), there will be an increase in the amount of solute in the ECF, which increases the ECF osmolarity. ECF osmolarity is higher than ICF osmolarity, which causes water to shift from ICF to ECF, decreasing ICF volume. Both ECF and ICF osmolarities are higher than normal and equal.
What happens to the plasma protein concentration and hematocrit during hyperosmotic volume expansion? Why?
Both plasma protein concentration and hematocrit will be decreased due to the increase in ECF volume. Also, hematocrit will decrease because of the water shift out of the red blood cells into plasma.
What are some examples of Hyposmotic Volume Expansion?
Syndrome of inappropriate antidiuretic hormone (SIADH)
What occurs during syndrome of inappropriate antidiuretic hormone (SIADH)?
Hyposmotic Volume Expansion:

Too much ADH leads to too much water reabsorption, and the excess water is retained and distributed throughout the total body water. The volume of water that is added to the ECF and ICF is in direct proportion to their original volumes. ECF and ICF volumes will be increased, and ECF and ICF osmolarities will be decreased.
What happens to the plasma protein concentration and hematocrit during hyposmotic volume expansion? Why?
Plasma protein concentration is decreased by dilution. However, the hematocrit is unchanged as a result of two offsetting effects: the concentration of RBCs decreases due to dilation, but RBC volume increases because water shifts into the cells.
What is the definition of renal clearance?
Renal clearance is the volume of plasma completely cleared of a substance by the kidneys per unit time.
What is the equation for renal clearance?
Cx = [U]xV/Px

Cx = clearance of X. Units are mL/min
[U]x = urine concentration of X
Px = plasma concentration of X
Renal clearance is the ratio of ___________ to ____________.
Renal clearance is the ratio of urinary excretion ([U]x*V) to plasma concentration.
Which substance is freely filtered across the glomerular capillaries, but not reabsorbed or secreted?
Inulin, which is used to determine the glomerular filtration rate (GFR).
What is the formula for Clearance Ratio?
Clearance ratio = Cx/Cinulin
What does Cx/Cinulin = 1.0 mean?
The clearance of substance x equals the clearance of inulin, and is neither reabsorbed or secreted.
What does Cx/Cinulin < 1.0 mean?

What substances show this property?
The clearance of x is lower than inulin. It is either not filtered, or it is reabsorbed.

Albumin, Na+, Cl-, HCO3-, phosphate, urea, glucose, and amino acids.
What does Cx/Cinulin > 1.0 mean?

What substances show this property?
The clearance of x is higher than inulin. It must be secreted.

Organic acids and bases, and sometimes K+.
What percentage of cardiac output do the kidneys receive?
25% of cardiac output.
What effect do the sympathetic nervous system and circulating catecholamines have on RBF and GFR? Why?
There is a decrease in both RBF and GFR.
Sympathetic nervous system produces vasoconstriction by activation of α1 receptors. α1 receptors are found on both afferent and efferent arterioles, but are much more prevalent on afferent arterioles.
What effect does Angiotensin II have on RBF and GFR?
Angiotensin II vasoconstricts both arterioles. This causes a decrease in RBF.
However, efferent arterioles are more sensitive to angiotensin II. Thus, at low levels of angiotensin II, there is an increase in GFR. A high level of angiotensin II produces a decrease in GFR.
What effect do prostaglandins have?
Prostaglandins, produced locally in the kidneys, cause vasodilation of both afferent and efferent arterioles. This increases RBF, and opposes the effects of the sympathetic NS and angiotensin II.
What effect does dopamine have on renal arterioles?
At low levels, Dopamine dilates renal arterioles, and has a protective (vasodilatory) effect on blood flow.
How can renal plasma flow (RPF) be estimated?
RPF can be estimated from the clearance of an organic acid para-aminohippuric acid (PAH).
What is the formula for Effective RPF?
Effective RPF = [U]PAH x V/[P]PAH = Clearance of PAH

Effective RPF is in ml/min
What is the difference between effective RPF and true RPF?
Effective RPF underestimates true RPF by ~10%. This is because we assume the concentration of PAH in the renal vein is zero, when in reality it is nearly zero.
What is the formula for RBF?
RBF = RPF/(1-Hematocrit)
What constitutes the most significant barrier of the glomerular capillary?
The basement membrane and its three layers: lamina rara interna, lamina densa, and lamina rara externa. The basement membrane does not permit filtration of plasma proteins, unlike the endothelial cell layer.
What is the Starling Equation?
GFR = Kf [(Pgc - Pbs) - πgc]

Kf = Hydraulic conductance or filtration coefficient

Pgc = Hydrostatic pressure in glomerular capillary

Pbs = Hydrostatic pressure in Bowman's space

πgc = Oncotic pressure in glomerular capillary
What is Kf (filtration coefficient)? What are the two factors that contribute to Kf?
The filtration coefficient is the water permeability or hydraulic conductance of the glomerular capillary wall.

The two factors that contribute to Kf are the water permeability per unit of surface area and the total surface area.
What other substances, besides inulin, can estimate GFR?
Creatinine is the closest substance. It is freely filtered, but is also secreted to a small extent. The clearance of creatinine slightly overestimates the GFR.

Blood urea nitrogen (BUN) and serum creatinine concentration are also used to estimate GFR.
What is the filtration fraction? What is the normal value?
Filtration fraction = GFR/RPF

The normal value is about 0.20 or 20%.
What is the formula for filtered load?
Filtered Load = GFR* [P]x
What is the formula for excretion rate?
Excretion rate = V x [U]x
What is the formula for Reabsorption of Secretion rate?
Reabsorption or Secretion Rate = Filtered load - Excretion Rate
At what plasma glucose concentrations does glucose start to be excreted in the urine?
What is this point called?
At plasma glucose concentrations above 200 mg/dL.

This is called threshold.
What is Tm?
Tm (transport maximum) is the plasma glucose concentration when all glucose carriers are saturated and cannot reabsorb any more. This occurs at plasma concentrations above 350 mg/dL.
What is splay?
Splay is the difference between threshold and transport maximum (Tm).
What are some causes of glucosuria?
- In diabetes mellitus, the filtered load of glucose exceeds the reabsorptive capacity (plasma [glucose] is above Tm)

- During pregnancy, GFR is increased, which increases the filtered load of glucose to the extent that it may exceed the reabsorptive capacity.

- Congenital abnormalities of the Na+-glucose cotransporter lead to decreases in Tm.
How is urea reabsorbed?
Urea is reabsorbed by simple diffusion, in most segments of the nephron.
What percentage of PAH is filtered across the glomerular capillaries?
<10%. Ninety percent of the PAH in blood is bound to plasma proteins. Only the unbound portion is filterable. The filtered load increases linearly as the unbound concentration of PAH increases.
What happens when PAH carriers reach Tm?
When Tm is reached, there can be no further increase in the secretion rate of PAH.
What drug uses the PAH transporter for secretion?
Penicillin.
At what urine pH does the HA form of a weak acid predominate?
Why is there more "back-diffusion" from urine into blood at this ph?
At acidic urine pH.

There is more "back-diffusion" from urine into blood because the uncharged HA form can diffuse across the cells. The A- form of a weak acid cannot diffuse.
At what urine pH does the A- form of a weak acid predominate?
At alkaline urine pH.

There is less "back-diffusion" from urine to blood, and excretion of the acid is increased.
What does [TF/P]x = 1.0 indicate?
The [TF/P]x ratio compares the concentration of a substance in tubular fluid to its concentration in systemic plasma.

When [TF/P]x = 1.0, it means that the concentrations are equal. This can mean a few things:
- The ratio was measured in Bowman's space for a freely filtered substance (and no reabsorption or secretion occurred yet)
- Reabsorption of the solute has occurred, but reabsorption of water has occurred in exactly the same proportion.
What does [TF/P]x < 1.0 indicate?
The reabsorption of the solute must have been greater than reabsorption of water.
What does [TF/P]x > 1.0 indicate?
There are two possible meanings:
- There has been a net reabsorption of the solute, but solute reabsorption has been less than water reabsorption.
- There has been a net secretion of the solute into tubular fluid.
How can water reabsorption be calculated?
Water reabsorption can be calculated from the value of [TF/P]inulin.
What equation corrects for water reabsorption?
What would a value of 0.3 mean?
[TF/P]x/[TF/P]inulin is a double ratio that corrects for water reabsorption.
A value of 0.3 means that 30% of the filtered load of the solute remains in the tubular fluid, or 70% has been reabsorbed.
The reabsorption of which ion is the most important? Why?
The reabsorption of sodium (Na+) is the most importnat function the kidney has. Sodium is the major cation of the ECF compartment. The amount of Na+ in ECF determines the ECF volume, which in turn determines plasma volume, blood volume, and blood pressure.
What percentage of Na+ reabsorption occurs in the proximal convoluted tubule?
67% (two-thirds) of the filtered load is reabsorbed. It is isosmotic reabsorption.
Which part of the nephron reabsorbs 25% of the filtered load of Na+?
Thick ascending limb of the loop of Henle. This region is impermeable to water.
Which portion of the nephron is responsible for Na+ balance?
The late distal convoluted tubule and collecting ducts, which also reabsorb the final 3% of the filtered load.
Which portion of the nephron does aldosterone act on?
The late distal convoluted tubule and collecting ducts.
In the early proximal tubule, what is Na+ reabsorbed with?
In the late proximal tubule?
In the early proximal tubule, Na+ is reabsorbed primarily with HCO3- and organic solutes such as glucose and amino acids.
In the late proximal tubule, Na+ is reabsorbed primarily with Cl-.
What are the cotransport mechanisms in the luminal membrane of the early proximal tubule?
Na+-glucose (SGLT), Na+-amino acid, Na+-phosphate, Na+-lactate, and Na+-citrate.
What is the countertransport or exchange mechanism in the luminal membrane of the early proximal tubule?
Na+-H+ exchanger.
What two exchangers exist in the late proximal tubule?
Na+-H+ exchanger and Cl-formate anion exchanger, driven by the high tubular fluid Cl- concentration.
If there is an increase in GFR (and therefore an increase in filtered load of Na+), how does the nephron maintain glomerulotubular balance?
Glomerulotubular balance ensures that a constant fraction of the filtered load is reabsorbed by the proximal tubule. When the GFR is increased, there is more fluid filtered. This leads to an increase in πc (oncotic pressure of peritubular capillary), which leads to increased reabsorption.
During infusion of isotonic NaCl (ECF volume expansion), what is the mechanism that maintains glomerulotubular balance?
An increase in ECF volume decreases the plasma protein concentration, and increases the capillary hydrostatic pressure. Both of the changes in these forces lead to a decrease in fractional reabsorption of isosmotic fluid in the proximal tubule.
During diarrhea or vomiting (ECF volume contraction), what are two mechanisms that maintain glomerulotubular balance?
- A decrease in ECF volume increases plasma protein concentration, and decreases the capillary hydrostatic pressure. This leads to an increase in fractional reabsorption of isosmotic fluid.
- Decrease in blood volume and arterial pressure activates the renin-angiotensin-aldosterone system. Angiotensin II stimulates Na+-H+ exchange in the proximal tubule, and thereby stimulates reabsorption of Na+, HCO3-, and water.
What is the result of activation of renin-angiotensin system during ECF volume contraction?
Because angiotensin II mechanism specifically stimulates HCO3- reabsorption (along with Na+ and water), ECF volume contraction causes contraction alkalosis (metabolic alkalosis secondary to volume contraction).
What is the thin descending limb permeable to?
The thin descending limb is permeable to water and small solutes such as NaCl and urea.
What is the thin ascending limb permeable/impermeable to?
The thin ascending limb is permeable to NaCl and impermeable to water.
What percentage of filtered Na+ is reabsorbed by the thick ascending limb?
25%, although the thick ascending limb (and distal tubule) are load-dependent (the more Na+ delivered, the more it reabsorbs).
What is the mechanism for reabsorption of Na+ in the thick ascending limb?
The luminal membrane contains a Na+-K+-2Cl- cotransporter.
Why is the Na-K-2Cl cotransporter considered electrogenic? What happens because of this?
The cotransporter transports all three ions (Na, K, and Cl) into the cell of the thick ascending limb; Na is extruded from the cell by the Na-K ATPase, and Cl and K diffuse through channels in the basolateral membrane.

A portion of the K, however, diffuses back into the lumen. Thus, the cotransporter brings slightly more negative than positive charge into the cell. This results in a lumen-positive potential difference across the cells of the thick ascending limb. This is the driving force for the reabsorption of divalent cations such as Ca and Mg.
How do the loop diuretics work?
Look diuretics are organic acids that are related to PAH. At physiologic pH, the loop diuretics are anions that attach to the Cl- binding site of the Na-K-2Cl cotransporter.
What is the [TF/P]na and [TF/P]osm for the fluid that leaves the thick ascending limb?
[TF/P]na < 1.0
[TF/P]osm < 1.0
What is the mechanism of reabsorption of filtered Na in the early distal tubule?
The mechanism is an Na-Cl cotransporter in the luminal membrane.
How do thiazide diuretics work?
The thiazides are organic acids, which are anions at physiologic pH. They bind to the Cl site of the Na-Cl cotransporter and prevent it from cycling.
What are the two major cell types of the late distal tubule and collecting duct? What do they do?
Principal cells are involved in Na reabsorption, K secretion, and water reabsorption.
α-Intercalated cells are involved in K reabsorption and H secretion.
What is the mechanism of Na reabsorption in the principal cells?
The luminal membrane of the principal cells contain Na channels, through which Na diffuses down its electrochemical gradient.
What does aldosterone do to increase the reabsorption of Na?
The steroid hormone, which is able to diffuse into the cell and is transferred to the nucleus, directs the synthesis of specific mRNAs. These mRNAs then direct the synthesis of new proteins that are involved in Na reabsorption by the principal cells, which include the Na channel itself, Na-K ATPase, and enzymes of the citric acid cycle.
What are the renal mechanisms that regulate Na excretion?
Sympathetic nerve activity
Atriopeptin (ANP)
Starling forces in peritubular capillaries
Renin-angiotensin-aldosterone system
How does Sympathetic nerve activity regulate Na balance/excretion?
Sympathetic activity is activated by the baroreceptor mechanism in response to a decrease in arterial pressure. It causes vasoconstriction of afferent arterioles and increased proximal tubule Na reabsorption.
How does atriopeptin (ANP) regulate Na excretion?
ANP is secreted by the atria in response to an increase in ECF volume. It causes vasodilation of afferent arterioles, vasoconstriction of efferent arterioles, increased GFR, and decreased Na reabsorption in the late distal tubule and collecting ducts.
How does the renin-angiotensin-aldosterone system regulate Na excretion?
The system is activated in response to decreased arterial pressure. Angiotensin II stimulates Na reabsorption in the proximal tubule, and aldosterone stimulates Na reabsorption in the late distal tubule and collecting ducts.
What are 5 things that cause K to shift into cells, and cause hypokalemia?
Insulin
α-Adrenergic antagonists
β2-Adrenergic agonists
Alkalosis
Hyposmolarity
What are 7 things that cause K to shift out of cells, and cause hyperkalemia?
Insulin deficiency
α-Adrenergic agonists
β2-Adrenergic antagonists
Acidosis
Hyperosmolarity
Cell lysis
Exercise
How does insulin stimulate K uptake into cells?
Insulin increases the activity of Na-K ATPase.
What happens to the K balance during alkalemia? Acidemia?
In alkalemia, the H+ concentration is decreased: H+ leaves the cells and K+ enters the cells, producing hypokalemia.
In acidemia, H+ concentration in blood is increased: H+ enters the cells and K+ leaves the cells, producing hyperkalemia.
Why is there generally no K+ shift during respiratory acidosis or respiratory alkalosis?
Because these conditions are caused by a primary disturbance of CO2. CO2 is lipid soluble, so it freely crosses cell membranes and needs no exchange with K+ to preserve electroneutrality.
When would metabolic acidosis not cause a K+ shift?
When the metabolic acidosis is caused by an excess of an organic acid (i.e. lactic acid, ketoacids, or salicylic acid).
What are the effects of activating adrenergic receptors?
Activation of β2-adrenergic receptors by β2-agonists (i.e. albuterol) increases the activity of the Na-K ATPase, causing a shift of K into the cells, and possibly producing hypokalemia.

α-Adrenergic receptor activation causes a shift out of cells, and may produce hyperkalemia.
Which cells reabsorb K in the distal tubule and collecting ducts? Which cells secrete K?
What are the mechanisms of the reabsorption and secretion?
α-Intercalated cells reabsorb K through H-K ATPases in the luminal membrane.
Principal cells secrete K via Na-K ATPase and K channels.
What are the three effects that aldosterone has on the secretion of K+?
1. Aldosterone induces the synthesis of more luminal membrane Na channels.
2. Aldosterone increases the quantity of Na-K ATPase
3. Aldosterone increases the number of K+ channels in the luminal membrane.
How and where is phosphate reabsorbed?
70% of the filtered load is reabsorbed in the proximal convoluted tubule. 15% is reabsorbed in the proximal straight tubule (right before loop of henle). 15% of the filtered load of phosphate is excreted.

Phosphate reabsorption is accomplished by an Na-phosphate cotransporter in the luminal membrane of the proximal tubule cells.
How does PTH regulate phosphate excretion?
PTH inhibits the Na-phosphate cotransporter.
How is Ca reabsorbed in the thick ascending limb?
Like Na, 25% of the filtered load of Ca is reabsorbed in the thick ascending limb. Due to the lumen-positive potential difference, Ca is reabsorbed in a paracellular route (between cells).
Where is magnesium reabsorbed the most in the nephron?
Mg2+ is reabsorbed most in the thick ascending limb, where 60% of the filtered load is reabsorbed, in comparison to the proximal tubule, which only reabsorbs 30%.
What is the two step process of countercurrent multiplication?
The single effect, the first step, refers to the function of the thick ascending limb. In the TAL, NaCl is reabsorbed via the Na-K-2Cl cotransporter. Due to the permeabilities of the loop of Henle, the result of the single effect is to decrease the osmolarity of the ascending limb, and increase the osmolarities of the interstitial fluid and descending limb.

The second step is the flow of tubular fluid. Fluid continuously flows through the nephron, and the new fluid that enters the descending limb will have an osmolarity of 300 mOsm/L. The high osmolarity fluid in the descending limb (created by the single effect) is pushed down toward the bend of the loop of Henle.
What are the steps of urea recycling? Where does it occur?
Urea recycling occurs in the inner medulla.
1. In the cortical and outer medullary collecting ducts, ADH increases water permeability, but not for urea. Water is reabsorbed, urea remains behind.

2. Urea concentration increases.

3. In the inner medullary collecting ducts, ADH increases both water and urea permeability.

4. Urea diffuses down its concentration gradient into the interstitial fluid in the inner medulla, where it is added to the corticopapillary osmotic gradient.
What is the difference between countercurrent multiplication and countercurrent exchange?
Countercurrent multiplication is an active process that establishes the corticopapillary osmotic gradient. Countercurrent exchange is a purely passive process that helps maintain the gradient.
What are the three effects of ADH on the renal tubule?
1) increases the water permeability of the principal cells of the late distal tubule and collecting ducts
2) increases the activity of the Na-K-2Cl cotransporter of the thick ascending limb
3) increases urea permeability in the inner medullary collecting ducts.
What are the receptors for ADH? What type of protein regulates the action of ADH?
V2 receptors for ADH on the principal cells.
Gs protein.
What is the water channel controlled by ADH?
Aquaporin 2 (AQP2)
What do you use to treat SIADH?
Demeclocycline, which inhibits the ADH action on the renal principal cells.
What do you use to treat central diabetes insipidus? Nephrogenic diabetes insipidus?
In central DI, treatment consists of administration of an ADH analogue, such as 1-deamino-8-D-arginine vasopressin (dDAVP).

In nephrogenic DI, treatment consists of thiazide diuretics. Thiazide diuretics inhibit Na-Cl cotransport in the early distal tubule, preventing dilution of the urine in this segment. As more NaCl is excreted, the urine is less dilute than it would be without treatment. Thiazide diuretics also produce a decrease in GFR and decrease in ECF volume. The decrease in ECF volume causes an increase in proximal tubule reabsorption via effects on Starling forces. The combination of less water filtered and more water reabsorbed in the proximal tubule means that the total volume of water excreted is decreased.
What does it mean when free water clearance (CH2O) is zero? When does this occur?
When free water clearance = 0, no solute-free water is excreted. Urine is isosmotic with plasma (isosthenuric). This can occur during treatment with a loop diuretic, where NaCl reabsorption is inhibited in the thick ascending limb.
What does it mean when free water clearance (CH2O) is positive? When does this occur?
When CH2O is positive, free water is being excreted.
This occurs when ADH levels are low or ADH is ineffective and the urine is hyposmotic.
What does it mean when free water clearance (CH2O) is negative? When does this occur?
When CH2O is negative, free water is reabsorbed in the late distal tubule and collecting ducts.
This occurs when ADH levels are high and the urine is hyperosmotic.