Renal Physio and Diuretics 2 Flashcards
In ThAL of Loop, what is at luminal membrane; basolateral? Comment on charges, in between cells, and the drugs that work at this level? of note?
Luminal membrane: Na-K-2Cl cotransporter mediates the ionic uptake (25% of filtered Na, 20% of filtered K);
basolateral: Na-K ATPase with Cl and K efflux (latter two generate lmen positive potential difference across ThAL tubular epi)
Between cells: driving force for Ca and Mg because of lumen positive potential difference;
Drug: furosemide blocks the cotransporter
Of note: thick and thin ascending limb of loop of Henle IMPERMEABLE to water, even if ADH is around (allows for dilution of tubular fluid and dilute hypoosmotic urine)
More stuff on THaL?
- Active reabsorption of solutes in medullary THaL generates counter-current multiplication of solute concentration differences, or gradient, going from cortex to papilla (can go from 300 mOsm in cortex to 1200 in papilla);
- In collecting duct: reabsorption of water, resulting from osmotic equilibration of tubular fluid with interstitium, generates a concentrated, hyperosmotic urine with osmolarity of up to 4 times greater than plasma (this depends on function of CORTICAL AND MEDULLARY ThAL)
Preservation of normal EFC volume achieved by
ability of kidney to concentrate or dilute osmolarity of urine in response to ECF volume and expansion
Ratio of urine to plasma osmolarity means what when =1, >1, <1? What is free water?
=1: urine is isotonic;
1: concentrated or hypertonic urine (kidney responding to minimize and correct ECF volume contraction and hyperosmolarity by eliminating solute in excess of water)
Free water is water not osmotically obligated to remain in the tubular fluid due to the presence of solutes
Free water clearance is; define the terms;
rate at which the kidney can retain or eliminate water free of solutes (rate in urine flow, V, - osmotic clearance, Cosm);
Cosm = (Uosm x V)/Posm
V and Cosm levels differ, meaning what for ADH?
ADH goes up with V < Cosm; ADH says same at V = Cosm; ADH goes down at V > Cosm
Facts about early distal tubule at luminal and basolateral membrane; drug that works here; what is this segment called?
5% of filtered Na taken up at early distal tubule
- Na-Cl cotransporter luminally; basolateral with Na-K ATPase and Cl channel
- Thiazide diuretcs competitively interact with Cl for occupancy at Cl binding site in Na-Cl cotransport protein;
- Cortical diluting segment (along with cortical ThAL)
Late distal tubule and CD facts, what happens at luminal and basolateral membrane; what does aldo do? Relationship of Na and K here?
- 3% of filtered Na taken up here; site which regulates the amount of Na and K in the urine
- Na channel in and K channel out luminally; Na-K ATPase basolaterally;
- aldosterone is a steroid hormone from the adrenal cortex which regulates Na reabsorption in this region; aldo can diffuse into cell from blood across basolateral membrane, bind to IC receptor to form receptor-aldosterone complex, which enters the nucelus and induces mRNA ranscription fo membrane transport proteins mediating transcell Na reabsorption;
aldo leads to more Na-K ATPases in basolateral membrane as well as more K channels in luminal membrane - Na rebasorption functionally coupled to K secretion, thanks to obligate coupling medated by Na-K ATPase;
What do amiloride and triamterene do?
Block and decrease Na uptake from tubular fluid at late distal tubule and CD (this would inhibit amount of K in urine);
K SPARING DIURETICS!!
What is spironolactone?
- Steroid and aldo receptor antagonist (inhibits Na reabsorption and K secretion across late distal tubule and CD), a K SPARING DIURETIC!!
- Competes with aldo for complex formation with its receptor
- However, ONLY WORKS if there is sufficient circulating aldo for spironolactone to induce an increased amount of Na and decreased amount of K in the urine (thus, patients have to be on a LOW Na diet!!)
