Diuretics Flashcards
Describe how water and salts are reabsorbed in the proximal convoluted tubule
What else is secreted here
Majority of Na, glucose, AA, HCO3 reabsorbed here
-NaKATPase on basal side
-NaH exchanger => H secretion
Weak acids and bases secreted here (drugs)
Describe how water and salts are reabsorbed in the TALoH
-why is this possible
What diuretic acts on what channel here
What are some examples
Na reabsorbed, water NOT reabsorbed here
- NaKATPase on basal side
- NKCCT (inhibited by LOOP DIURETICS)
- K circulates between tubule and cell => +ve fluid that forces Na, K, Ca, Mg through to blood, independent of Na uptake
- Cl channel => blood
- driven by hypertonic medulla (countercurrent mechanism)
Furosemide
Torasemide
Describe how water and salts are reabsorbed in the distal convoluted tubule
Na and water reabsorbed here
- NaCl2 exchanger (inhibited by THIAZIDE DIURETICS)
- NaKATPase on basal side
- Cl channel, K channel => blood
-K circulates between cell and ISS, independent of Na uptake
Indapamide
Bendroflumethiazide
Metolazone
Describe how water and salts are reabsorbed in the collecting duct
Na and water reabsorbed here
K secretion reduced
-ENaC, ROMK (K SPARING DIURETICS)
-NaKATPase on basal side
How do loop diuretics work
When is it used
What are the main 5 side effects and why
What congenital disease has similar side effects and why?
If less Na is reabsorbed via NKCCT => less water reabsorbed in DCT, CD
-due to smaller osmotic gradient between CD, medulla=> more dilute urine
Edema
- heart failure (increased venous pressure)
- hepatic cirrhosis => ascities
- renal disease (protein lost via kidneys)
- hepatic disease (less albumin produced)
SE
HYPOKALEMIA
-increased overall NaK exchange in CD
METABOLIC ALKALOSIS
-decreased plasma volume without proportional decrease in HCO3 => [HCO3] increases but amount doesn’t
HYPOCALCEMIA, HYPOMAGNESIA
-driven by net movement of circulating K, decreased K gradient => decreased uptake of Ca, Mg
OTOTOXICITY
-NKCCT similar to Cl channel in inner ear
HYPOVOLEMIA
-too much diuresis
Neonatal Barrter syndrome => loss of function of NKCCT
How do thiazide type diuretics work
What are the CV effects?
When is it used
What are the main side effects
Block NCl2 cotransport in DCT
Reduce plasma volume, venous return, TPR
Transient decrease in CO
HTN due to VD effect
SE
HYPOKALEMIA
-increased overall NaK exchange in CD due to decrease uptake
HYPERGLYGEMIA
-NaK exchange needed => insulin. Harder if hypokalemic
HYPERURICAEMIA
-increase urate reabsorption
What are the 3 mechanisms that explain why diuresis => metabolic alkalosis
- volume depletion
- hypokalemia
- increased Cl secretion
Volume depletion (low GFR) => less NaCl reaches macula densa => increased Ang2 released => increased NaH exchanger activity in PCT => increased Na uptake, H secretion
Hypokalemia => NaH exchange in PCT => increased Na uptake, H secretion
Increased Cl loss => increased HCO3 reabsorption
How do diuretics lead to hypokalemia
Diuretics inhibit reauptake of Na
Increased Na delivery to CD => increased uptake by ENaC
Gradient established by ATPase
Increased movement of Na into cell => -ve fluid in CD => drives K out by ROMK
Diuretics also increase the amount of fluid in CD => K washed away quickly, not enough time to move into A Intercalated cells via KH exchange
What diuretics can be used to prevent hypokalemia
How do they work, how would you use them?
What are the side effects of K sparing diuretics
Not used in isolation, used with loop for
- heart failure
- renal disease
- hepatic disease
Spironolactone- aldosterone receptor antagonist
-very slow onset => aldosterone upregulates NaKATPase and ENac via protein synthesis
Amiloride, triamterene- block ENaC => reduced Na uptake, K secretion
Hyperkalemia
What diabetic drug also has a diuretic effect
How does it work
Empagliflozin - SGLUT blocker in PCT
-increased glucose in urine keeps water in tubule
Good add on, action is insulin dependent
