Renal 2 Flashcards
How do aquaretics affect the action of ADH?
Decrease the ability of ADH to increase H2O permeability of the late DT and CD
What are saluretics? What are the 4 classes?
Drugs which decrease reabsorption of solutes in 1 or more segments of the nephron:
Carbonic anhydrase inhibitors
loop diuretics
thiazide diuretics
K-sparing diuretics
What is an osmotic diuretic?
Drug which enters the tubular fluid by glomerular filtration and is neither reabsorbed nor secreted along the nephron. The increased osmotic pressure within the tubule inhibits H20 reabsorption resulting in a more voluminous diuresis.
- What is the mechanism of loop diuretics?
- Why are they considered most efficacious?
- Why does loop diuretic use result in excessive K secretion in the urine?
- Inhibit Na/K/2Cl cotransporter in thick ascending limb –> decrease Na/K/Cl reabsorption
- They induce the largest diuresis (FE-Na = 25%)
- Compensatory mechanisms downstream in the late DT/CD couples Na reabsorption with K secretion
- Where do thiazide diuretics act?
- Mechanism of action?
- How are they similar to loop diuretics?
- Cortical talH/Early DT
- Inhibit Na/Cl cotransporter –> Decrease Na and Cl reabsorption
They also inhibit proximal tubule carbonic anhydrase - Increased excretion of K due to compensatory Na reabsorption (they are obligately coupled)
- Where do potassium sparing diuretics work?
- Mechanism of action?
- What other diuretics would you combine with them? Why?
- Late DT/CD
- Block Na chnls in late DT/CD –> Block the obligate functional coupling of Na reabsorption and K secretion
- Either a loop diuretic or thiazide diuretic. K sparing diuretics will decrease the amount of Na reabsorbed in the late DT/CD –> increase the volume of diuresis while maintaining blood K concentration
Describe the mechanism by which loop diuretics increase the time necessary to rid the body of excess fluid intake.
Remember: CH20 = V - Cosm
The loop diuretics increase osmolar clearance (Cosm). Therefore, less free water is excreted based on the following equation CH20 = V - Cosm and it takes more time to excrete fluid in excess of solute
In a volume contracted patient, why do loop diuretics increase free water clearance?
A healthy kidney would attempt to concentrate the urine. In a patient on loop diuretics, there is a lesser countercurrent gradient, and therefore an inability to concentrate urine. This results in less negative free water clearance
What is a risk of thiazide diuretic use in volume expanded patients?
(Remember: CH20 = V - Cosm)
What is a major risk?
Because they decrease the ability to excrete free water, it will take a longer time to decrease the excess volume. Therefore, major risk: hyponatremia
What is the countercurrent multiplication ion concentration dependent on?
The magnitude of transcellular solute reabsorption in the medullary thick ascending limb of Henle
Describe the process by which thiazide diuretics decrease free water clearance ability
Remember: CH20 = V - Cosm
block solute reabsorption in the DT –> decrease the ability to dilute the urine. Osmolar clearance increases therefore decreasing free water clearance
(CH20 = V - Cosm)
What solutes absorbed in the cortical early distal tubule participate in the counter current concentration gradient?
Solutes that are reabsorbed into the cortex do not contribute to the ion concentration gradient.
Describe the mechanism of the carbonic anhydrase inhibitors
Inhibit luminal CA –> decrease intracellular H+ –> Na/H exchanger function decreases –> limit reabsorption of Na + promote diuresis
What effect do CA inhibitors have on urine pH?
Increased pH
Describe the contents of the diuresis induced by CA inhibitors
Increased excretion of Na, K, and HCO3- in an alkaline urine
What are the major complications of CA inhibitor use?
Hypokalemia (K loss in urine) and metabolic acidosis (bicarb loss in urine)
What are the current uses of CA inhibitors now that they are obsolete as diuretics?
Used to decrease intraocular volume and pressure
What can CA inhibitor-induced metabolic acidosis lead to?
Ammonia generated from renal metabolism is diverted from the urine to accumulation in the ECF creating the risk of hepatic encephalopathy
Osmotic diuretics work by influencing the following 3 parameters. Explain their influence.
1) Osmotic pressure
2) Tubular fluid flow
3) Renal blood flow
(1) Non reabsorbable solutes increase the osmotic pressure –> opposes isotonic reabsorption of Na and H2O.
(2) Increased flow of isotonic tubular fluid decreases Na and Cl reabsorption in the LOH and distal tubule.
(3) There is increased blood flow to the renal medulla –> decreases the osmotic gradient decreasing urine concentrating ability.
What is the most widely administered osmotic diuretic?
Mannitol
What are four loop diuretics and what do they act upon?
Furosemide
Bumetanide
Torsemide
Ethacrynic acid
inhibit the Na-K-Cl cotransporter in the talH
What is the FE of Na for CAI?
< 5%
What are the 3 therapeutic indications of mannitol?
Drug OD (drugs eliminated via urine) shock (treat acute renal failure) Increased intraocular/intracranial pressure
How is hyponatremia caused by loop diuretics? How is it corrected?
Remember: CH20 = V - Cosm
The kidney has an inability to excrete H2O in excess of solute; Hyponatremia may be corrected with water restriction
What is the mechanism causing hypokalemia in a patient on loop diuretics and thiazide diuretics?
Excess Na is delivered to the distal tubule –> K secretion and elimination
What 4 changes in ECF solute concentration can result from loop diuretic induced ECF volume contraction?
alkalosis (high HCO3), Hyperuricemia, Increased BUN, Increased serum creatinine
What are the 6 diuretics that belong to the thiazide and thiazide-like classes, respectively?
Thiazides: C, H
Thiazide-like: C, M, Q, I
Chlorothiazide Hydrochlorothiazide Chlorthilidone Metolazone Quinethazone Indapamide
What is a risk factor of mannitol use?
Pulmonary edema
What are the 5 indications for loop diuretic use?
Two involve edema…
One involves the liver…
One involves calcium…
The last involves drugs…
Crises involving pulmonary edema edema from HF cirrhosis Hypercalcemia Drug toxicity
What solutes are increased in the diuresis of a patient on loop diuretics?
Na, K, Cl, Mg, Ca
A loss in body weight is seen on administration of loop diuretics but then the body weight plateaus. Why is this?
Compensatory Na reabsorption in the proximal tubule counters the Na excretion induced by the loop diuretics
Describe the mechanism of thiazide and thiazide-like diuretics
Block the Na-Cl cotransporter –> decrease transcellular Na and Cl reabsorption in the early DT
What serious side-effect can be caused by loop diuretics especially in the presence of aminoglycoside antibiotics?
Ototoxicity
As side effects, how can thiazide and thiazide-like diuretics affect the blood levels of the following?
K Na acidosis or alkalosis? Uric acid BUN serum creatinine Calcium
Hypokalemia-diabetes
hyponatremia
contraction alkalosis
hyperuricemia
increased BUN
increased serum creatinine
hypercalcemia
What is the primary use of thiazide diuretics?
What are 3 secondary uses?
Primary Use: HTN
Secondary Use:
Chronic edema due to cardiac insufficiency
Idiopathic hypercalciuria
nephrogenic diabetes insipidus
What are the 3 potassium sparing diuretics?
Spironolactone, Amiloride, Triamterene
What is the mechanism of spironolactone?
Sprionolactone competes with aldosterone for the aldosterone receptor –> downregulates proteins necessary for Na reabsorption and K secretion in the LDT and CD
What ability of the kidney do the thiazide diuretics limit? What does this put the patient at risk for?
The ability to dilute the urine; Hyponatremia
What is a major risk of K sparing diuretic use?
hyperkalemia
What type of mechanism is induced by the kidney to compensate for loss of Na due to thiazide diuretics?
Increased sodium reabsorption in the proximal tubule
What is the main clinical application of the potassium sparing diuretics?
Used in combination with thiazide or loop diuretics to minimize K depletion while controlling hypertension
What is required to make spironolactone induce diuresis?
Presence of aldosterone in the blood
What is the mechanism of action of amiloride and triamterene?
Amiloride and triamterene both block Na channel and Na/H exchanger in the luminal membrane of the LDT and CD
There are several secondary clinical applications of K sparing diuretics.
1) Control edema caused by what 3 conditions?
2) What hormonal irregularity?
3) What ionic abnormality?
4) What random condition?
Control edema caused by CHF, cirrhosis, and nephrotic syndrome;
Primary/Secondary aldosteronism;
Idiopathic hypercalciuria;
Li-induced polyuria
By what transporter are thiazide/loop diuretics secreted into the tubular fluid across the luminal membrane? Amiloride and triamterene?
Thiazide/Loop Diuretics
–Passively thru the organic anion transporter
Amiloride/Triamterene
–Actively thru the organic cation/H+ transporter
What side effects are associated with spironolactone use?
Androgen receptor antagonism resulting in gender-specific effects (male - gynecomastia, etc; female - amenorrhea etc)
What are the 5 factors determining the quantity of of diuretic present at its site of action?
Plasma concentration, RBF, Glomerular Filtration, Tubular secretion, Tubular Fluid Concentration
Order the diuretics from greatest to least FENa
Loop > Thiazide > CAI > K-sparing
Why are higher doses of diuretic needed to give to a patient with kidney failure?
Organic anion metabolites build up in the circulation because they cannot adequately be secreted by the kidney. Therefore, there is a greater competitition for the OA transport. Higher doses of diuretics can outcompete the higher levels of metabolites
Why are higher doses of diuretic needed in a patient with nephrotic syndrome?
In nephrotic syndrome, excess protein is in the tubular filtrate. This protein absorbs the diuretic limiting its action. Therefore, higher doses are needed.
