Pharm --Renal/Diuretic Flashcards
___ contracts from 1/2 of Total body fluid (TBF) to 1/3 of TBF in adults
ECF
What is solute concentation/osmolarity of ICF and ECF
approx. 300mOsm/L
ICF is __% of body weight
ECF is __% of body weight
Blood volume is __% of body weight
ICF = 40%
ECF = 20%
Blood volume = 7%
K is high ___ the cell
Na is high ___ the cell
K = high inside Na = high outside
–b/c Na/K pump sends K inside and Na out; K can leak out, Na can’t come in
Daily urine output is ___L which is ___% of GFR
1-2L
0.5-1% of GFR
___ is the major solute determining ECF osmolarity
Sodium
Low Na in ECF causes what compensatory change in ECF volume?
Decreases to maintain osmolarity
Can sodium be:
- -filtered?
- -secreted?
- -reabsorbed?
- -excreted?
- -Duh
- -NO!
- -yes
- -yes
What is normal GFR (mL/min)
125ml/min
Normal plasma Na concentration:
140mM
Normal plasma bicarbonate concentration:
24mM
% of Sodium reabsorbed at:
- -Proximal tubule
- -TAL of Loop
- -Distal tubule
- -66%
- -25%
- -6-8%
Nephrotic syndrome is excess filtration and excretion of ___
Albumin
–leads to decreased plasma oncotic pressure
Most filtered bicarbonate is reabsorbed here
Proximal tubule
This portion of the nephron has “leaky” epithelium and is unable to maintain an osmotic gradient.
Proximal tubule
–66% of tubular filtrate is reabsorbed
Loop of Henle: thin descending, thin ascending, TAL
Which is/are impermeable to water?
thin ascending, TAL are impermeable to water (even in presence of ADH)
What portion of the nephron is the physiological origin of positive free water clearance?
Ascending limb of Loop
–no water reabsorption –> hypoosmotic tubular fluid
Circulating Aldosterone hormonally regulate this mechanism at this portion of the nephron.
Sodium reabsorption in the late distal tubule
Early vs. late distal tubule:
Which portion is permeable to water?
Late distal tubule = permeable when induced by interaction with antidiuretic hormone (ADH) –> concentrates urine by reabsorbing water
What is normal filtration fraction?
FF = GFR/RPF = 0.2
What is used to measure GFR? Why?
Inulin clearance
–It is not reabsorbed or secreted, so filtered = excreted
Excretion = Filtration + Secretion - Reabsorption
How is renal handling of Potassium (K) different in low K vs. high K diets?
In what portion of the nephron does this regulation occur?
Low K = no secretion, more reabsorption
High K = high secretion, less reabsorption
Distal tubule and cortical collecting duct
How do alkalosis and acidosis affect potassium (K) secretion?
Alkalosis –> increased K secretion
Acidosis –> decreased K secretion
How do diuretics (except K sparing) cause hypokalemia?
Block of Na reabsorption upstream (TAL for loop and early DT for thiazide) causes increased Na secretion at late DT which induces K secretion
What is negative free water clearance?
What hormone affects it?
Water in tubule reabsorbed back into circulation
- -induced by ADH
- -generates hypertonic urine
How does volume expansion affect Aldosterone levels?
Volume expansion –> low aldosterone –> less Na reabsorption –> less water reabsorption –> dilute urine
What is the mechanism of aquaretics?
Decrease ability of ADH to increase water permeability in late distal tubule and collecting duct –> dilute urine
What are 4 osmotic diuretics?
Mannitol
Excess glucose
Urea
Isosorbide
How do loop diuretics affect positive and negative free water clearance?
–Decrease positive free water clearance (directly, by increasing osmotic clearance in TAL)
–Decrease negative free water clearance (indirectly, by reducing ADH sensitivity (ability to concentrate urine) in the medullary CD from reduced medullary gradient)
How do thiazide diuretics affect positive and negative free water clearance?
Only affects positive free water clearance (prevent salt reabsorption –> increased tubular concentration –> increased water clearance)
–Does not affect negative free water clearance (concentrating urine)
Relative maximal fractional excretion of Na in:
- -PT
- -TAL
- -DT
- -CD
TAL = 25% --loop DT = 8% --thiazide PT = 5% --CA inhibitor, osmotics CD = 2% --K+ sparing diuretics
Carbonic anhydrase inhibitors [increase/decrease]:
- -tubular H+
- -tubular pH
- -Na/H exchanger rate
- -Intracellular carbonic acid formation
- -tubular H+ = decrease
- -tubular pH = increase –> alkaline urine
- -Na/H exchanger rate = decrease
- -Intracellular carbonic acid formation = decrease
Carbonic anhydrase can induce
- -[hyper/hypo] kalemia
- -metabolic [acidosis/alkalosis]
- -Hypokalemia
- -Metabolic acidosis – excess bicarb excretion
Why are osmotic diuretics used in shock and surgery?
Prevent acute renal failure – maintain urine flow
What is the molecular mechanism of loop diuretics?
–Compete w/ chloride for occupancy in 1 of 2 Cl binding sites of Na-K-2Cl cotransporter in luminal membrane of TAL
How long does it take for loop diuretics to induce diuresis?
IV = within minutes Orally = within an hour
How do you prevent hyponatremia caused by chronic use of loop diuretics?
Limit water consumption – prevent volume expansion b/c loop diuretics reduce positive free water clearance
When loop diuretics are used together with aminoglycoside antibiotics (gentamycin), there is a markedly increasked risk for what complication?
Ototoxicity – hearing loss
What are loop diuretic effects on:
- -Calcium
- -Magnesium
- -Potassium
- -Increase calcium excretion
- -Increase magnesium excretion
- -Increase potassium excretion
What is the molecular mechanism of thiazide diuretics?
Inhibit Na-Cl cotransporter in luminal membrane of early DT
A patient on [loop/thiazide] diuretic is more at risk for hyponatremia
Thiazide diuretic – imbalance in renal volume regulation (since it only affects + (diluting urine ability) and not - (concentrating urine ability) free water clearance)
What is the only segment of the nephron that reabsorbs glucose?
Proximal tubule
Is mannitol reabsorbed and/or secreted?
Neither
Do loop diuretics increase or decrease the ability of the kidney to excrete water in excess of solutes?
Decrease – lowers positive free water clearance = less ability to dilute urine
What are the 2 substituted benzothiazide drugs?
- -Chlorothiazide
- -Hydrochlorithiazide
What are the 4 thiazide-like drugs?
- -Chlorthalidone
- -Metolazone
- -Quinethazone
- -Indapamide
The early distal tubule is [permeable/impermeable] to water
Impermeable – even in the presence of ADH
Do thiazide diuretics affect the kidney’s ability to correct for:
- -increase in ECF?
- -decrease in ECF?
–Increased ECF – YES = reduces ability to excrete water in excess of solutes (dilute urine/ + free water clearance) after excess water consumption
–Decreased ECF – NO = doesn’t affect ability to concentrate urine
How is calcium excretion affected by:
- -Loop diuretics?
- -Thiazide diuretics?
- -Amiloride (K-sparing)?
- -Loop = increased excretion
- -Thiazide = increased paracellular reabsorption –> decreased excretion
- -Amiloride = decreased excretion
Assuming Na consumption is constant, loop and thiazide diuretics induce what compensatory mechanism?
–Compensatory increase in Na and water reabsorption in proximal tubule (upstream) –> maintain sodium balance, but not enough to maintain water –> diuresis w/o hyponatremia
Diuretics cause contraction alkalosis through what 2 mechanisms?
- -ECF volume contraction w/o increased bicarb elimination
- -ECF volume contraction induces increased PT reabsorption of bicarb (to increase water reabsorption?)
Which class of diuretics can be used to prevent kidney stone formation?
Thiazide – reverese idiopathic hypercalciuria
How do thiazide diuretics affect GFR?
Decreases GFR
Thiazide drug intereractions with digitalis and quinidine increase the risk of what events?
- -Digitalis – arrhytmia
- -Quinidine – torsade des pointes
Compete with Aldostere for binding to an intracellular receptor –> decrease amount of Aldosterone-Receptor (AR) complex –> decrease proteins that maintain Na reabsorption and K secretion
Also, indirectly inhibit Na/H exchanger
This is the molecular mechanism of what drug(s)?
Spironolactone
Inhibit channel mediated Na reabsorption at the late DT –> decreased intracellular Na –> decreased Na/K ATPase –> decreased intracellular K –> decreased K secretion
Also, directly inhibit Na/H exchanger
This is the molecular mechanism of what drug(s)?
Amiloride
Triamterene
This diuretic is a competitive antagonist of androgen receptors which:
- -in males, cause: gynecomastia, erectile dysfunction, loss of libido
- -in females, cause: amenorrhea, oligomenorrhea, breast soreness
What is it?
Spirinolactone
