what are the two different types of cells in the collecting ducts, and what are their functions?
(1) principal cells: re-absorption of Na+ and secretion of K+ (2) intercalated cells: secretion of H+
what is the function of the tight junction between the cells of the collecting ducts?
transport of water and ions can be individually regulated by hormones
what controls Na/Cl absorption in the in the collecting ducts?
what controls water re-absorption in the collecting ducts?
anti-diuretic hormone (ADH/vasopressin)
what does Aldosterone do? what blocks it?
Na/Cl reabsorption and K excretion. Effect is blocked by K sparing diuretics
explain the quick effect/delayed effect of aldosterone
(quick effect): stimulation of the Na+/H+ exchanger (binding to membrane aldosterone receptors). (delayed effect): binding to cellular receptors → mediator proteins that activate sodium channels
what does ADH do? (what blocks it?)
↑ water reabsorption (stimulates V2 receptor which results in increased numbers of aquaporins or water channels in the apical membrane.) Blocked by Lithium carbonate, Demeclocycline, Colchicine (in class he said we just need to know that it can be blocked. I don't trust him.)
Explain K+ balance in the collecting ducts, and how it relates to the tubular membranes and Na+ (in his words)
The higher permeability of the luminal membrane for Na depolarizes the luminal membrane but not the basolateral membrane. This creates a lumen-negative trans-epithelial potential difference. This in turn creates an important driving force for the secretion of potassium via K-channels. Delivery of more Na to this part of the kidney augments depolarization of the luminal membrane, enhances the lumen negative potential difference and facilitates K excretion
explain K+ balance when non-k-sparing drugs are used
K loss will ↑ when ↑ Na reaches the collecting ducts (this happens with thiazide and loop diuretics) (my notes say: membrane on side of urine is depolarized, but the cells lining the UT and blood are not. So between the urine and interstitium, there is a bigger trans-epithelial potential difference. The more Na that reaches that part of the kidney (collecting duct), will further facilitate K secretion. With more Na in urine, there is a bigger diff between luminal side and basolat side, which forces K back into urine.)
explain how K+ balance and K-sparing diuretics work
K loss will be ↓ when Na reabsorption is ↓ in the collecting ducts (this is what K-sparing diuretics do)
how does Spironolactone work? where is it absorbed/how well is it absorbed? Side effects?
works by competing with aldosterone. Well absorbed from GIT. SEs are GI upset, hyperkalemia, gynaecomastia, menstrual disorders, testicular atrophy, peptic ulcers
which K-sparing diuretic has an active metabolite? what is the name of the a.m.?
Spironolactone does, the a.m. is called canrenone (SPIRO CAN do it!)
which K-sparing diuretic's onset takes several days?
Spironolactone (going in a spiral takes longer than a straight line)
how does Amiloride work? where/how is it absorbed? how is it excreted? side effects?
Directly decreases activity of the pump(Na/K). Poorly absorbed from GIT. It is excreted mostly unchanged. SE is hyperkalemia (Ami wont let much change her, and she doesnt care that you can't stomach her. she'll punch you right in the pump)
how does Triamterene work? where/how well is it absorbed? How is it excreted? Side effects?
Directly decreases activity of the pump(Na/K). Well absorbed from GIT. excreted partly unchanged. SE is hyperkalemia (Tri-s to be like Ami, but that's why it partly changes itself in order to convince itself to punch you in the pump. However, when not around any, is easy to stomach)
what are K-sparing diuretics used to treat?
decrease hypokalemia secondary to other diuretic use (CHF), treat edema and ascites (think hepatic disease and portal hypertension) (special K for your liver, eat it up and your belly will swell and your heart will explode)
when are K-sparing diuretics less effective?
poor diuretic effect is increased when sodium load or aldosterone concentrations are high
what are the aldosterone-mediated effects on the tubule? (6)
[remember, aldosterone is interested in absorbing Na+Cl and excreting K]. (1) activate Na channels (2) redistribute Na channels to luminal membrane (3) De novo(new) synthesis of Na channels (4) Activation of K/Na ATPase(pump) (5) Redistribution of K/Na ATPase to the basolateral membrane (6) De novo(new) synthesis of K/Na ATPase
which drug increases long-term survival in canine CHF and why? (NOTE: I have no idea where I got this. So. Feel free to ignore at your own risk)
spironolactone, because it competes with aldosterone (aldosterone inc Na--> inc water--> inc BP. so inhibiting these dec edema and cardiac workload) (spiro the dragon helps all fellow animals)
They are filtered through the glom but not reabsorbed in the tubules, and act on those parts of the nephron that are freely permeable to water (proximal tubule - descending limb of the loop of Henle, collecting duct). Prevents reabsorption of H2O by dec. osmotic gradient.
what is the primary effect of osmotic diuretics, and what is the secondary effect?
primary--> osmotic pull keeps water in the tubules. secondary--> dec Na reabsorption (Na is leaked back from leaky membrane to stay with water bc of diff osmotic gradient)
2 clinical indications of osmotic diuretics?
(1) acutely raised intracranial or intraocular pressure (2) prevention of acute renal failure (reduced GFR - urine flow ceases)
what are the side effects of osmotic diuretics in the body?
transient expansion of extracellular fluid (I have written: pull fluid from all your tissues, so transient dehydration of all of them.)
the "specific therapy" of acute kidney injury is what? examples?
Remove the cause! If toxins--> antidotes. If infectious cause --> antimicrobials
supportive therapy in acute kidney dz--> fluid therapy. Explain why we do this
correction of hydration status, acid-base balance and electrolyte status
*supportive therapy--> management of oliguria or anuria. How do we do this? (order(not sure if actually order or just how he worded it) in which we do things-specific drugs named)
Start with furosemide(loop diuretic) when lack of urinary output. Then use osmotic diuretics. Then use fenoldopam (a dopamine agonist which works better than dopamine because it doesnt get degraded so quickly- works on D1 receptors which cause vasodilation for inc GFR), then diltiazem (a Ca++ antagonist which causes vasodilation to inc GFRs)
supportive therapy--> management of polyuria. How do you do this? (not specific)
do by monitoring fluid and electrolyte therapies
supportive therapy--> treatment of uremic complications (what are the two complications, basic idea on how you tx it?)
(1) vomiting--> anti-emetics and inhibitors of gastric acid secretion (2) hypertension--> adjust fluid administration rates- diuretics - anti-hypertensives
Chronic kidney disease is most common in who?
most common in ageing cats, but also seen in dogs or other animals
Chronic kidney disease is a renal dz that leads to _________ and then _________
renal insufficiency and then renal failure
Chronic kidney disease--> pathological changes occur to what structure? regardless of what?
Regardless of the site of initiating renal injury, pathological changes will occur to the glomerulus (it all goes back to glom, baby)
Chronic kidney disease--> how is severity of dz usually reflected?
reflected in the magnitude of proteinuria (urine protein-to-creatinine ratio) (if proteinuria is persistent higher than 0.5, def a prob, he said, but this isnt in notes)
what is the RAAS? If you have kidney dz, what do you wanna do with the RAAS?
Renin-Angiotensin- Aldosterone System (hormone system that regulates blood pressure and water (fluid) balance. Angiotensin causes vasoconstriction and Aldosterone causes water and sodium retention) If you have kidney dz, then, you wanna INHIBIT it, because it will then REDUCE the blood pressure and there will be LESS retination of water and salt, which puts less burden on the kidneys
what are the 4 ways to inhibit the RAAS system?
(1) Angiotensin-converting-enzyme inhibitors (2) Angiotensin receptor blockers (losartan -telmisartan) (3) Aldosterone receptor blockers (spironolactone) (4) Renin inhibitors (used in humans and not extensively yet in dogs: aliskirine)
Angiotensin receptor blockers--> what are the receptors these drugs act on? Describe the properties of the receptors
(1) AT1. The Classic effects of angiotensionII work here. vasoconstriction--> aldosterone and vasopressin release - sodium and water retention (sympathetic facilitation). cell prolif--> left ventricular hypertrophy, nephrosclerosis, endothelial dysfunction. (2) AT2. usually does opposite of the classical AT1, in order to limit the detrimental effects of AT1 activation. Actions are: vasodilation - sodium excretion - anti proliferative effects
what is/are the drug(s) used to block angiotensin receptors?
TELMISARTAN, losartan (ppl need to stop being so TENSE about their TANs)
look at slide 38 chart
telmisartan shit ( (1)vasoconstriction+sodium and water retention+symapthetic stim+pos inotropy--> hypertension and arrythmia. (2) cellular prolif/growth+ECM protein regulation--> vascular and cardiac hypertrophy, modeling, nepherosclerosis. (3) endothelial dysfunction, modification of LDL--> atherosclerosis )
which receptors does telmisartan bind to? what are the strong effects it exerts?
Binds strongly to AT1 (the classic effect receptor) to reverse effects by inhibiting. This causes strong antihypertensive effects
what are the properities of telmisartan? (hydro or lipophilic? is there prot binding? how is it absorbed, and how is it metabolized?)
Lipophilic, binds reversibly to plasma proteins, oral bioavail is 33% in cat, and is GLUCORONIDATED (oddly enough, cats still do well with it) (my FAT CAT loves to EAT PROTEIN and GLUCOSE, and will TEL MI when he wants to)
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