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107 Cards in this Set

  • Front
  • Back
% of CO that goes to Kidneys
20-25%
Force behind solute reabsorption
Na/K ATPase
Carbonic Anydrase role in Kidney
NaHCO3 reabsorption
Afferent arteriole cells release
Renin
Role of Macula Densa
Measures Na concentration in distal tubule & communicates via ANS to Granular cells
Counter Current Multiplier Mechanism
Allows for H2O reabsorption by setting up gradients
Controls absorption of water in the collecting ducts
ADH
Controls active reabsorption of NaCl in distal tubule
Aldosterone
MOA of Thiazide diuretics
Prevent NA reabsorption in distal tubule
Effect of ADH on collecting tubule and collecting duct
ADH increases permeability to water to increase reabsorption
Mode of Na reabsorption in collecting duct
Via epithelial NA channels
Actions on epithelial Na channels
Aldosterone - Stimulatory

Amiloride - Inhibitory
MOA of Osmotic Diuretics
Modify Filtrate content
What is the main function of the kidney?
Remove wastes, regulate volume, electrolyte and pH of the extracellular fluid
What components comprise a nephron?
Glomerulus, Proximal tubule, loop of Henle, distal convoluted tubule, and collecting duct
What is the main driving force for reabsorption of solutes and water from the lumen?
Na+/K+ ATPase in the basolater membrane of the tubule
How is Na+ transported into the proximal tubule?
Sodium enters the lumen as part of the ultrafiltrate.
What stimulates epithelial Na+ channels to reabsorb Na+ from lumen?
Aldosterone
What inhibits epithelial Na+ channels that reabsorb Na+?
Amiloride
How does Aldosterone promote Na+ reabsorption from epithelial cells into the blood?
Stimulates synthesis of Na+/K+ transporters to increase sodium reabsorption from cells into the blood
What is the Effect on K+ and H+ levels by Aldosterone/ADH
As Na+ is transported out of the lumen and epithelial cell, K+ and H+ are transported into the lumen resulting in increased K+/H+ excretion.
Which drugs selectively act on transporters in the tubule?
There are no rugs that are selective for transporters.
What is the purpose of the counter current multiplier system?
To promote H2O reabsorption by setting up gradients
What controls absorption of water in the collecting ducts?
ADH/Vasopressin
What controls active reabsorption of NaCl in the distal tubule?
Aldosterone
Which is more permeable to water, the ascending or descending loop of Henle?
The decending loop is much more permeable to water
What class of drugs inhibits NaCl cotransport in the distal tubule?
Thiazide Diuretics
What drug inhibits Aldosterone?
Spironolactone
How do osmotic diuretics act?
They modify the osmolarity of the ultrafiltrate, promoting water excretion
What function does Carbonic Anhydrase have?
Carbonic Anhydrase combines HCO3 and H+ ion together to form CO2 and H2O and transports them across the epithelial cell where they are converted back into HCO3 and H+ ion. The HCO3 is then transported back into the blood, thus conserving base.
Where does Carbonic Anhydrase act?
Mostly in the proximal tubule
How much fluid has been reabsorbed by the time it ultrafiltrate passes through the Loop of Henle?
60-70%
What are the loop diuretics?

Where do they act?
Furosemide
Bumetanide

They act on the thick ascending limb inhibiting the Na+K+/Cl-2 carrier
What are the Carbonic Anhydrase inhibitors?

Where do they act?
Acetazolamide

They act on the proximal tubule by increasing excretion of HCO3 and accompanying Na+, K+, and water.
Which are the most common diuretics used?
Thiazides and Loop Diuretics
Which class of diuretics are also know as "high ceiling" diuretics
Loop diuretics
Carbonic Anhydrase Inhibitors are more commonly used for what conditions
Epilepsy
Glaucoma
Loop Diuretics are used for what conditions?
Acute Pulmonary Edema
Hypercalcemia-Inc. Ca exc.
CHF
Nephrotic Syndrome
HTN
Renal Failure
Chemical Intoxication-Wash out
Thiazides are used for what conditions?
Renal Failure
Hypercalcemia
Nephrogenic Diabetes Insipidus
HTN
K+ Sparing diuretics are used for what conditions?
HTN
Augmentation of other antihypertensives
Where do thizide diuretics act?
They target the Cl- site of the NaCl transporter blocking NaCl reabsorption
Examples of Xanthine diuretics
Caffeine
What side effects could thizide diuretics have?
Could precipitate a gouty attack by impairing Uric Acid clearance

May cause Hypokalemia
Role of macula densa cells
Respond to changes in rate of flow and composition of distal tubule fluid, and control renin release from granular cells. Located in distal convoluted tubule.
Role of granular cells
Release renin in response to decreased Na+ in distal tubule or decreased renal perfusion. Located in afferent arteriole
How much Na+ reabsorption occurs in the proximal convoluted tubule?
60-70%
Where does carbonic anhydrase work?
In the proximal convoluted tubule
The only class of diuretic drugs that work on the PCT
Carbonic anhydrase inhibitors
Net effect of Carbonic anhydrase inhibitors
Plasma HCO3 declines beacause o fincreased urinary excretion of HCO3, Na+, K+ and water with acoompanying metabolic acidosis
Current uses of Carbonic anhydrase inhibitors
Glaucoma - Decreased AH formation

Epilepsy - Unusal forms of infantile elpilepsy
Limitation of carbonic anhydrase inhibitors
Diuretic effect is limited to suppply of bicarbonate
Most powerful class of diuretics?
Loop diuretics
Which class of diuretics may precipitate a gouty attack?
Thiazides
Where do Thiazides exert their action?
Distal tubule
Thiazides
Chlorothiazide
Hydrochlorothiazide
Chlorthalidone
Indapamide
Metazolone
Uses of Thiazides?
HTN
CHF
Edema
Hypercalciuria to prevent stone fromation
Nephrogenic DI
What causes Thiazide induced metabolic alkalosis?
Retention of HCO3
Volume contraction & Concentration of NaHCO3
Loss of H+ ion
What drug reaction history is significant when giving thiazides?
Sulfa drug sensitivity

Can cause SJS
What electroyte imbalance is possible with Thiazides?
Hypokalemia

TDP
Arrythmias/V fib
What is the relationship betwen diabetes and Thiazides?
Thizides increasing K+ loss

K+ and Glucose are cotransporters, when K+ is lost Glucose is retained raising blood sugar levels
What is the relationship between Lithium levels and Thiazide use?
Lithium is a salt, and when Na+ is lost through Thiazide action, Lithium is retained resulting in increased levels and possible toxicity
Why do Thiazides cause K+ depletion?
K+ is exchanged for Na+ in collecting tubule resulting in increased K+ excretion
What is the site of action of Thiazides in the Distal Tubule?
Thiazides act on the CL-site of Na+/Cl- transporter to block NaCl reabsoprtion
What other class of diuretics are Thiazides structurally similar to?
CAI

Both have sulfur in structures
Why could Thiazides precipitate a gouty attack?
Thiazides and UA both compete for the same transporter.

Thiazides prevent UA from being transported into the lumen and can cause buildup of UA
How do we treat hypokalemia associated with Thiazide use?
K+ supplements

Use of K+ sparing diuretic
What is a bid storage site for K+ in cells?
Proteins with -COOH
Adverse effects of Thiazides?
Hypokalemia
SJS
Increased UA levels
Metabolic Alkalosis
What loop diuretic is safe to give to people with sulfa sensitivity?
Ethacrynic Acid
What class of diuretics are Loops derived from?
Thiazides

Loops have sulfur in structure
Loop diuretic site of action?
Thick ascending loop of Henle
Action of Loop diuretics?
Block NaK2Cl transport AND disrupt counter-current multiplier system

"Double whammy"
What is the significance of the NaK2Cl transporter?
It is the driving force behind the counter-current multiplier system
Which is more efficacious as a diuretic, Thiazides or Loops?
Loops have greater efficacy, causing more NaCl excretion.
What are the potential toxicities of Loop diuretics
Hypokalemia
Matabolic Acidosis
Lithium retention/toxicity
Temporay deafness due to inner ear distrubance
May displace Protein bound drugs
1st choice of drug to treat stage 1 HTN?
Thiazide diuretic

Especially if renally impaired
Conditions the loop diuretics are used to treat?
Used cautiously in conjuction w/ sodium restriction in edema caused by CHF, liver disease, kidney failure
HTN, especially if renally impaired
Hypercalcemia-cardiac, muscle issues
Rank from most efficacious to least: Thiazides, K sparing, Loops
Loops
Thiazides
K+ Sparing
Effect of Adrenal cortical tumor?
Increased aldosterone & corticosteroids

Decreased K+ levels
Why would a K+ sparing diuretic be used to treat a person with Adrenal cortical tumor?
Adrenal tumor would cause K+ wasting, and K+ sparing diuretic would help retain K+
How does a Pituitary tumor affect K+ levels?
Tumor would release ACTH that drives Adrenal cortex, increasing release of aldosterone and causing hypokalemia.
What is the action of ADH?
It increases the # of aquaporins, promoting H2O reabsorption
How does Aldosterone exert its effect?
It increases Na+ reabsorption from the collecting tubule and increases the # of Na+/K+ transporters to increase Na+ transport back into blood from basolateral membrane
What are the clinical uses of K+ sparing diuretics?
Adjunt to K+ wasting diuretics
Treatment of refractory edema
Hyperaldosteronism
Heart Failure
Possible adverse effects of K+ sparing diuretics?
Hyperkalemia
Hormonal effects
Menst. Irreg.
Impotence
Dec. Libido
Gynecomastia
What is the rationale for combining diuretics?
Furosemide prevents Na+ absorption in TAL, and Thiazide also prevents DT from compensating by absorbing more than it normally would.

The combination is more effective than either individually
Result of chronic exposure to diuretics?
Upregulation of transporters to compensate
Compensation for K+ loss when using K+ wasting diuretic?
K+ sparing diuretic or K+ supplement

NOT BOTH!!!!
Action of osmotic diuretics?
Pulls H2O from intracellular space to dilute diuretic

Filtered in the glomerulus but not reabsorbed, increasing H2O excretion along with smaller Na+ excretion
Clinical uses for osmotic diuretics?
Used ito maintain renal tubular flow in trauma, hemolytic reactions, & toxic poisoning
Used emergently for increased ICP or intraocular pressures
How do osmotic diuretics treat heart failure?
They don't. The are NOT useful for treating heart failure associated with Na+ reabsorption
Possible adverse effects of osmotic diuretics?
CV overload due to increased volume

Hypersensitivity - give small dose 1st
Where do CAI's act?
In proximal tubule on carbonic anhydrase
Effects of CAI's
Increased excretion of NaHCO3 an retention of H+ ion resulting in acidosis and increased K+ excretion
Clinical uses of CAI's
Alkalinizing urine - H+ loss
Glaucoma - Decrease AH production
Epilepsy - Suppress neuron firing
Adverse effects of CAI's
Cross sentitivity to sulfa drugs

Hypokalemia
A Pt. that has been taking Acetazolamide for 4 dyas may develop what?
Tolerance to diuretic action of CAI
Thiazides
Chlorothiazide
Hydrochlorothiazide
Indapamide
Bendroflumethazide
Clorthalidone-Thiazide like
Meazoloe-Thiazide like
Sulfanyl Derivative Loops
Furosemide
Bumetanide
Torsemide
Phenoxyacetic Acid Derivatives
Ethacrynic Acid
Aldosterone receptor blockers
Spironolactone
Eplerenone-More specific for aldosterone receptor
Na+ Channel Blockers
Amiloride
Triamterene
Osmotic Diuretics
Mannitol
Sucrose
Urea
Glycerol
Carbonic Anhydrase Inhibitors
Acetazolamide
Dichlophenamide
What would be an effective adjunct treatment with Thiazides or Loops for someone with High uric acid levels?
Uricosurics, which promote urate excretion in the urine.
What are the uricosurics?
Probenecid
Sulfinpyrazone
What diuretic classes contain sulfur meoities?
CAI's
Thiazides
Loops (Except Ethacrynic Acid)