PPT 15: Diuretics Flashcards
Exam 3
What are the Proximal Tubule Targets?
NaCl and NaHCO3
Which drugs target Proximal Tubule Targets?
Carbonic anhydrase inhibitors (block NaHCO3 reabsorption)
Caffeine (weakly blocks adenosine receptors in PCT (Na+))
_______ is an example of a Carbonic anhydrase inhibitor
Acetazolamide
Body fluids are kept at a constant osmolality of _____ via a _________ mechanism in the ____
300 mOsm/kg
countercurrent
proximal tubule
The _____ is responsible for the secretion of larger substances (drugs) into luminal fluid
S2 - straight segment
______ is an impermeable solute that increases osmolality
mannitol
The _______ loop of henle is responsible for water reaborption
descending
The ______ loop of henle is impermeable to water
ascending
What is the pump that transports NaCl and K in the ascending loop of henle?
NKCC2 - sodium, potassium, 2 chloride
- all pumped from urine to thick ascending limb
The excess ____ in the urine of the ascending loop of henle drives ____ out of the urine and into the blood
K+ (charge gradient)
Mg++ and Ca++
What is the MOA of loop diuretics? What is an example?
Selectively inhibit NaCl reabsorption in the thick ascending limb (TAL)
- Reduction in NaCl absorption
- Diminish lumen positive potential - Increase secretion (loss) of Mg2+ and Ca2+ in urine
Lasix
What diruertics should be avoided in patients with sulfa alergies?
Loop diuretics (lasix) and thiazides (HCT)
What is reabsorbed in the distal convoluted tubule? By what?
Ca++, by PTH
What is the MOA of thiazides?
- Inhibit NaCl transport in DCT
- Some inhibition of CA activity
- HCT
Carbonic anhydrase inhibitors ___ pH, while loop diuretics and thiazides ___ pH
Decrease, increase
______ is the final site for sodium reabsorption
collecting tubule
______ is the most important site for potassium secretion
collecting tubule
The collecting tubule contains what 2 cell types?
Principal and intercalated
What is the role of the principal cells in the collecting tubule?
Builds up (-) charge in lumen
- more Na+ in than K+ out
- drives Cl- out through paracellular route
_____ is the channel responsible for Na+ and water reuptake in the collecting tubule
ENaC - epithelial sodium channel
What is the role of the intercalated cells in the collecting tubule?
H+ removal into urine
Exchange bicarb for Cl- in blood
Differentiate between the 2 types of K+ wasting diuretics
Some block NaCl
- Cl- leaves via paracellular route
Some block NaHCO3
- HCO3 can’t exit via paracellular route
- Drives increased K+ depletion
Diuretics upstream result in excess ___ in CT
Na+
Aldosterone is secreted by the ______
adrenal cortex
What is the effect of aldosterone at the collecting tubule?
Increase Na+ and water reuptake (ENaC) - increasing BP and vol
K+ sparing diuretics work by what MOA?
- Antagonize the effects of aldosterone - spironolactone
- Inhibition of sodium flux through ion channels in luminal membrane - amiloride
K+ sparing diuretics are most useful in states of _____
mineralocorticoid excess - Conn’s syndrome, Ectopic ACTH production
ADH (vasopressin) effects at the collecting duct
- Increases water reabsorption
- Adds preformed AQP2 to apical membrane
- Increases blood volume
- Makes more concentrated urine
ADH agonist vs antagonist
- Agonist: Vasopressin
- Antagonist: Conivaptan
What parts of the nephron are freely permeable to water?
PCT and descending loop
_____ is used mainly to reduce intracranial pressure
mannitol
- also for rhabdomyolysis and radiocontrast agents
Mannitol works by countering the _____
osmotic force - more urine ouput, less Na+ reabsorption
What is the etiology and treatment for DI?
Insufficient ADH
Thiazide diuretics
The hypertonic medullary interstitium is in the _____
descending loop of henle
What are the uses for Carbonic Anhydrase Inhibitors?
Glaucoma
Alkalinization of urine
Metabolic alkalosis
Acute Mountain Sickness
What is the loop diuretic that isn’t a sulfanamide?
Ethacrynic acid
What are the 3 ways GFR is regulated?
- Adjust blood flow
- Alter capillary surface area
- Control arteriole diameter
What are the steps that occur if GFR is increased?
GFR increased
1. Receptors - macula densa cells of JGA detect increased NaCl and water
2. Juxtoglomerular apparatus is the control center - decreased secretion of NO
3. Effectors - afferent arteriole decreases blood flow through the glomerulus
4. GFR decreased - back to homeostasis
What are the actions of the nephron?
- Glomerular filtration
- Tubular reabsorption
- Tubular secretion
Rate of excretion =
Rate of excretion = filtration rate + secretion rate - reabsorption rate
Most of the filtrate is reabsorbed in the ____
PT
What are the components of the neprhon?
- Glomerulus
- PCT
- Descending loop of henle
- Ascending loop of henle
- DCT
- Collecting tubule
- Collecting duct
______ is the hormone that acts at the collecting tubule, while _____ is the hormone that acts at the collecting duct
aldosterone
ADH
What are the 4 main targets of diuretics?
- Membrane transport proteins
- Water permeable segments of nephron
- Enzyme inhibition
- Interference with hormone receptors
What are the classes of diuretics?
- Carbonic Anhydrase Inhibitors
- Loop Diuretics
- Thiazides
- Potassium Sparing Diuretics
- Osmotic diuretics
The renal corpuscle is made of what 2 parts?
- glomerular capillaries (glomerulus)
- glomerular (Bowman’s) capsule
The _______ is the capillary system that surrounds the PCT and DCT, while the _____ surrounds the loop of henle
Peritubular capillaries
vasa recta
Podocytes are only found in the ____
cortex - glomerular filtration
The juxtaglomerular apparatus includes what 3 parts?
macula densa, juxtaglomerular cells, and extraglomerular mesanginal cells
The juxtaglomerular apparatus is located where?
the vascular pole of the renal corpuscle.
How does the juxtaglomerular apparatus regulate BP?
Regulates blood pressure by activating the renin-angiotensin-aldosterone system
The _____ monitors osmolality and fluid volume in the distal tubule and transmits info to JG cells (NO)
macula densa
_________ are the modified SM cells in the afferent arteriole that synthesize renin
Juxtaglomerular Cells
The nephron filters ___ and produces _____
blood, urine
