Lecture 11: CV Part 2 COPY Flashcards
What are the 5 functional zones of nephron?
Proximal Convoluted Tubule
Descending Loop of Henle
Ascending Loop of Henle
Distal Convoluted Tubule
Collecting Tubule and Duct
What generally happens in the proximal convoluted tubule?
most of filtered Na+, Sodium bicarb, potassium, water, and glucose/amino acids are reabsorbed.
Organic acids are also secreted.
Note: Medications do not work on this part of the kidney.
What generally happens in the descending loop of Henle?
Loop passes into the kidney’s medulla.
Water is extracted by osmotic forces found in the hypertonic medullary interstitium.
Osmolarity increases, aka salt concentration increases by 3x.
What generally happens in the ascending loop of Henle?
25% of NaCl is reabsorbed without water following, aka the diluting segment.
Location of the Na/K/2Cl cotransporter, so K returns to the cell.
Mg and Ca are reabsorbed via paracellular pathway.
What generally happens in the distal convoluted tubule?
10% of filtered NaCl is reabsorbed via thiazide-sensitive Na/Cl cotransporter.
Ca reabsorbed via Na/Ca exchanger, which is regulated via parathyroid hormone.
What generally happens in the collecting tubule?
Only responsible for 2-5% of NaCl reabsorption by the kidney.
Final site of NaCl reabsorption.
Site at which mineralcorticoids work.
Important site of K secretion by the kidney and where nearly all diuretic-induced changes in K balance occur!!!!
Contains principal cells which are for major sites of Na+, K+, and water transport regulated by aldosterone
What cells does aldosterone work on in the kidneys?
Principal cells.
What kind of transporter does the a principal cell have?
Na/K, generally pumping Na back into the blood, and K back into the urine.
What happens if a diuretic increases Na+ delivery to the collecting duct?
More potassium shifts of out the blood, so your urine concentration of K is much higher.
What are the water channels in principal cells called?
Aquaporins.
What hormone regulates aquaporins?
ADH/Vasopressin.
What does ADH do to an aquaporin?
Makes cells permeable to water, concentrating the urine.
Where do loop diuretics work on in the kidney?
Ascending loop
Why do we like loop diuretics?
They have the highest efficacy in diuretic effect, aka you take more, the more effect. They are sometimes known as high-ceiling diuretics.
What are the 3 loop diuretics?
Furosemide (Lasix)
Torsemide
Bumetanide (Bumex)
What is the MOA of a loop diuretic?
inhibition of Na/K/2Cl pump.
This causes a significant increase in the amount of sodium in the urine and therefore water in the urine.
Increased urinary Ca and Mg, but most Ca is reabsorbed later.
Can increase renal blood flow by increasing prostaglandin production.
Note: NSAIDs can reduce effect.
What is the PK of a loop diuretic?
may be administered orally or parenterally
have rapid onset of action, even in patients w renal insufiiciency
duration of action is 2 to 8 hours
secreted into urine by organic acid secretory system (PCT)
bumetanide and torsemide are much more potent than furosemide
What are the indications (therapeutic uses) for a loop diuretic?
Reducing edema (acute/chronic peripheral, acute pulmonary, good in emergencies due to rapid onset of action)
may also be used along with hydration to manage hypercalcemia
Also can treat hyperkalemia.
What are some contraindications for a loop diuretic?
Black Box Warning: Leads to profound diuresis with water and electrolyte depletion.
Hypersensitivity to sulfonamides.
Ototoxicity with hearing loss/vertigo, seen mainly when combined with other ototoxic drugs.
Hypovolemia, hypokalemia, hypomagnesemia.
Hyperuricemia (increase uric acid and can lead to gout attacks, therefore avoid in pt’s with high UA or hx of gout attacks)
Pregnancy C
What kind of patients should not a use loop diuretic?
People on other ototoxic drugs like aminogylcosides.
People with gout or high uric acid levels.
pregnant women (class C)
What are the thiazide drugs we learned?
Chlorothiazide (Diuril)
Chlorthalidone
Hydrochlorothiazide (HCTZ, most common)
Indapamide
Metolazone (most potent, inpatient only)
What are thiazide drugs a derivative of?
Sulfonamides.
What part of the kidney does a thiazide drug work on?
the thiazide sensitive Na/Cl cotransporter in the Distal convoluted tubule.
What is the MOA of a thiazide drug?
Decreases Na+ reabsorption, keeping more water in the urine. (done via inhibition of Na/Cl transporter)
Increases K+ loss in urine.
Loss of Mg w chronic use
Decreases urinary excretion of Ca, so serum Ca increases.
Reduces peripheral vascular resistance.
What is the PK of a thiazide drug?
Equal max effect, potency varies.
Oral
Exceptions:
Chlorothiazide has low lipid solubility, so it requires high dosages AND can be given parenterally.
Chlorthalidone has a half life of 50-60 hours, longest duration.
Metolazone is most potent, can be used in renal failure.
What are thiazide drugs also known as?
Low ceiling drugs. They have a max effect, unlike the loop diuretics, which are high ceiling.
Which thiazide can be given in renal failure?
Metolazone, the most potent.
Which thiazide would I use if I just wanted to give one dose every few days?
Chlorthalidone
Which thiazide would I use if I wanted to use the most common?
Hydrochlorothiazide, HCTZ.
Which thiazide would I use if I wanted an IV administration one?
Chlorothiazide.
How long does it take a thiazide to reach max/stable BP reduction?
1-3 weeks.
What system do thiazide drugs compete with in excretion? Implications?
Organic acid secretion, which means uric acid can build up.