2.1.2 Renal Handling of Urea and Uric Acid Flashcards
Reabsorption of urea in the collecting tubule is stimulated by:
an increase of circulating levels of ADH.
an efficient countercurrent multiplier system.
an increase in water reabsorption in the collecting tubule.
all of the above.
All of the above
In the distal nephron and the first sections of the collecting duct permeability for urea depends on several factors. When ADH is present, reabsorption of water increases urea concentration in the luminal fluid. When the fluid reaches the inner medullary collecting ducts, urea has attained a high concentration. The gradient drives transtubular reabsorption to the interstitium via facilitated diffusion through transporters present in the apical and basolateral membranes. Since water reabsorption is primarily responsible for the increased urea concentration gradient across the tubules, it is clear that reabsorption of urea depends on the water movements. There is an additional factor linking water and urea reabsorption: ADH, which stimulates water reabsorption in the collecting ducts, also activates the urea facilitated diffusion transporters in the medullary collecting ducts. So the presence of ADH, reabsorption of water, and an adequate countercurrent mechanism are essential for urea reabsorption (option d).
The following values were obtained from a patient before and after treatment with furosemide.
The GFR in the patient:
Increased by more than 25%
Decreased by more than 25%
Unchanged
Unchanged
To calculate GFR, the following equation is used:
GFR = UCR . V / PCR
Before furosemide, GFR = 117 mg/dl x 1.3 ml/min / 1.2 mg/ml = 126.7 ml/min.
After furosemide, GFR = 36.6 mg/dl x 4.5 ml/min / 1.3 mg/ml = 126.7 ml/min.
As shown, GFR is not affected by the use of the diuretic furosemide (option c).
What are some of the effects of acetazolamide?
Increased excretion of Na+ and bicarbonate
Increased secretion of K+ in distal nephron
Can result in metabolic acidosis
Where is uric acid secreted?
Proximal tubule middle segement
What are the effects of aquaretics?
Increased excretion of free water
Does not affect salt secretion
Does not affect H+ secretion
Where is uric acid reabsorbed?
Proximal tubule 1st and last segment
A 70-year-old man presents complaining of pain in his joints; especially his big toe. His serum showed elevated levels of uric acid. In this person, you would expect to see increased reabsorption and secretion of uric acid in which of the following regions of the kidney?
Proximal tubules
Uric acid in plasma is not bound to proteins and filter readily in the glomeruli; then, it is handled almost exclusively by the proximal tubules. Net reabsorption usually prevails, and under normal conditions, approximately 8 to 12% of the filtered uric acid load is excreted. However, the compound is also secreted.
Reabsorption occurs in the first and last segments of the proximal tubule, and secretion, in the middle segment of the proximal tubule.
What is a characteristic effect of spironolactone?
Decreased secretion of H+ and metabolic acidosis
What are the uses for thiazide diuretics?
Essential hypertension
HF
Edema
Renal lithiasis
What is the MOA of aquaretics?
Blocking V2 receptor on basolateral membrane of collecting tubule.
The following values were obtained from a patient before and after treatment with furosemide.
The rate of K excretion in the patient:
increased more than 2-fold with treatment.
increased less than 2-fold with treatment.
decreased more than 2-fold with treatment.
decreased less than 2-fold with treatment.
did not change with treatment.
Increased more than 2 fold
The rate of K+ excretion can be calculated by multiplying the urine volume in 24 hs and the concentration of K+ in urine.
So, before furosemide, K+ excretion rate = 1.87 L/day x 72 mEq/L = 134.6 mEq/day.
After furosemide, K+ excretion rate = 6.5 L/day x 82 mEq/L = 533 mEq/day.
So, after treatment with the diuretic, K+ excretion rate increase more than 2-fold.
What is the mechanism of action of thiazide diuretics?
Inhibition of the NaCl co-transporter in the distal tubule
Results in increased excretion of Na and Cl
What are the uses of furosemide?
Most effective diuretic
Treats HF
Hypertension
Pulmonary edema
What is the MOA of osmotic diuretics? (Mannitol)
Works on entire nephron
Uses osmotic action to increase excretion of H2O
What is the mechanism of action of a loop diuretic (furosemide)?
Inhibits the NKCC channel in the loop of henle
What are diuretics?
Compounds that cause diuresis
They deccrease volume of ECF
Affects salt and water excretion
What are normal plasma concentrations of uric acid?
Plasma: 4-6 mg/dL
The following values were obtained from a patient before and after treatment with furosemide.
Which of the following accounts for the fall in urine osmolarity after furosemide treatment?
Decreased permeability of the collecting ducts to water
Decreased water reabsorption in the proximal tubule
Reduced permeability of distal tubules to water
Reduced reabsorption of salt in the thick ascending limb of the loop of Henle
Reduced reabsorption of salt in the thick ascending limb of the loop of Henle
The fall in urine osmolarity after treatment with furosemide, depends on inhibition of the Na-K-2Cl transporter and a reduction in the reabsorption of salt in the thick ascending limb of the loop of Henle.
What does diuresis mean?
It is the term used to designate the increase in the volume of urine excreted
What are the uses for aquaretics?
How can decreased GFR effect urea handling?
Decreased GFR will lead to increased urea retention and increased BUN
Due to decreased urine flow and increased water transport
What is the MOA of amiloride?
Inhibition of the ENaC at the collecting tubule (apical side)
Leading to increased excretion of Na+
Decreased K+ secretion by decreasing electrical gradient at apical side
What are com uses for potassium sparing diuretics? (Amiloride and spironolactone)
In combination with other diuretics to prevent hypokalemia
Hypertension
What are the effects of ADH on Urea transport?
Increased water transport will lead to increased urea reabsorption at collecting tubules
Due to increased levels of ADH
What is the MOA of acetazolamide?
Site of action is proximal tubule
Inhibition of conversion to CO2 + H2O
What are the uses of carbonic anhydrase inhibitors?
Weak diuretics
Used to treat glaucoma
Correction of metabolic alkalosis
Profilaxis for acute altitude sickness
What is the MOA of spironolactone?
Inhibition of the Na/K pump on basolateral membrane of collecting tubule cells.
Leads to increased excretion of Na+
In a patient treated with furosemide:
the ability of the kidneys to concentrate the urine maybe impaired.
water diuresis will occur.
the fractional excretion of K+ will be reduced.
the epithelial Na channel in the distal tubule will be blocked.
the ability of the kidneys to concentrate the urine maybe impaired.
The ability of the kidney to concentrate the urine depends on the correct function of the countercurrent mechanism at the renal tubules. The countercurrent effect is based on maintaining a high salt concentration at the renal medulla. One of the main mechanisms involved in transporting salt into the renal medulla is the Na-K-2Cl co-transporter, located in the ascending limb of the loop of Henle. Furosemide is a diuretic that specifically inhibits the activity of the Na-K-2Cl co-transporter. Therefore, besides causing an increase in renal fractional excretion of Na+ and K+, furosemide secondarily impairs the efficiency of the kidney countercurrent mechanism (answer A).
Describe the handling of urea by the proximal tubule, descending loop on henle, and collecting tubule.
Proximal tubule - reabsorbs 50%
Descending loop - secretes 60%
Collecting tubule - reabsorbs 50%
60% of Urea is excreted
What are the effects of furosemide?
Increased excretion of Na+, K+ and Cl-
Increased secretion of K+ in distal nephron
Increased Ca2+ and Mg2+ loss in loop of henle
Decreased counter current mechanism
Increased H+ secretion in distal nephron
Can result in hypokalemia, hyponatremia, and hypomagnesemia
Metabolic alkalosis
