ADH and Diuretics Flashcards
How much plasma is filtered by the kidneys in a day?
180 L
Where in the kidney do the loop diuretics work?
the ascending limb of the LOOP of henle (LOOP)
Where in the nephron do thiazide diuretics work?
in the distal convoluted tubule
Where in the nephron do Potassium sparing diuretics work?
the cortical collecting tubule
Where is ADH active?
in the medullary collecting duct
Where in the nephrone do the osmotic diuretics work?
in the proximal tubule and/or the descending limb of the LOH
What are two examples of Loop diuretics?
furosemide (Lasix) and bumetanide
What do loop diuretics do?
they inhibit the Na/K/2 Cl pump in the thick ascending limb of the lOH
What percentage of Na is reabsorbed in this area - the thick ascending limb of the LOH?
about 25%
WHat happens in general to the osmolarity in the tubule of the thick ascending limb of the LOH?
It goes hypo-osmolar because Na, K and Cl are pumped out but water remains inside since there are no aquaporins here
What is the effect of the loop diuretics on osmolarity within the tubulet hen?
They prevent this decrease in osmolarity because they inhibit the Na, K and Cl from moving out of the tubule.
What effect do the loop diuretics have on Na, Cl and K excretion?
Increased NaCl excretion and increased K excretion because some of the increased nehron Na is exchanged for K in the cortical collecting tubule
What are the major uses of loop diuretics?
- pulmonary edema
- other edematous conditions (CHF)
- hyperkalemia
- acute renal failure
- anion overdose
Why aren’t the loop diuretics used for HTN?
Because htey have a much greater impact on systemic electrolyte levels than the thiazide diuretics and thus have more severe side effects
What are three thiazide diuretics?
chlorthalidone
hydrochlorothiazide
metalazone
What do the thiazides do?
they block the NaCl transporter in the distal convoluted tubule
What percentage of NaCl reabsorbtion occurs in the distal convoluted tubule?
not much - only 8%.
What do the htiazides to to Na, Cl and K excretion
increased NaCl excretion
increase K excretion because some of the increased Na is exchanged for K in the cortical collecting tubule
What are the major uses of the thiazides?
hypertension!
heart failure
nephrolithiasis caused by hypercalcemia
nephrogenic diabetes insipidus
What are the major side effects of the htiazides?
hyperglycemia hyperuricemia hypokalemia hyperlipidemia hyponatremia allergic reactions
Why do the thiazides cause hyperglycemia? Do you still use them in diabetics?
Thiazides are sulfonylureas and will bind to an SUR receptor on a potassium channel controlling insulin release
when it binds, the K channel opens and you get an efflux of K and you hyperpolarize the beta cell
This inhibits the beta cell’s release of insulin release
thus, increasing blood glucose
What are the potassium sparing diuretics?
spironolactone
eplerenone
amiloride
triamterene
What are the two mechanisms of the K sparing diuretics?
spironolactone and eplerenon are aldosterone receptor inhibitors
amiloride and triamterene inhibit Na exchange for K and H in the cortical collecting duct
What are the major uses of the K sparing diuretics?
hyperaldosteornism
prevent potassium wasting caused by other diuretics
What additional benefit do the aldosterone receptor inhibitors have in heart failure?
they prevent the fibrotic changes in the kidneys and heart caused by aldosterone (which is high in CHF)
What are the side effeccts of the K sparing diuretics?
hyperkalemia (duh) hyperchloremic metabolic acidosis Gynecomastia (spironolactone) acute renal failure (specific to triamterene and indomethacin) kidney stones
Vasopressin is the naturally occuring antidiuretic hormone, so what is the synthetic congener?
desmopressin
What are vasopressin and desmopressin used for?
diabetes insipidus
bed-wetting
How does ADH work?
It ultimately activates G protein coupled receptors in the collecting duct to recruit aquaporin channels
this makes water more likely to reabsorb , making urine more concentrated
What is the major osmotic diuretic?
mannitol
How does mannitol work?
it’s a big old sugar that doesn’t get reabsorbed (filtration rate = excretion rate), so it promotes H2O excretion by osmotic forces
What are the uses of mannitol/
reduce body water
reduce intracranial pressure
reduce intraocular pressure
What are some toxicities of mannitol?
extracellular volume expansion dehydration hperkalemia hypernatremia hyponatremia when renal function is low?
What is the major carbonic anhydrase inhibitor?
acetazolamide
Why is acetazolamide not really helpful as a diuretic?
because carbonic ahydrase is too important of an enzyme and works in a lot of places in the body
What do we use acetazolamide for?
glaucoma
produce urinary alkalinization
produce metabolic acidosis
to treat acute mountain sickness
What are the side effects of acetazolamide?
hyperchloremic metabolic acidosis
renal stones
renal potassium wasting
What is the major pathology related to the organic anion transporters?
gout - they transport small hydrophilic molecules into or out of the nephron, including urate (driven by symport or antiport exchane of molecules for dicarboxylates)
What drugs can we use to treat gout that act in the kidney? How do they work?
probenicid and sulfinpyrazone
they inhibit a renal OAT to facilitate the excretion - the uric acid doesn’t get reabsorbed
How does allopurinol work?
it blocks santhine oxidase so you don’t get xanthine ocnverted to uric acid
How does colchicine work for gout?
it’s a microtubule inhibitor with anti-inflamamtory properties
