Lecture 11: CV Part 2 (INCOMPLETE)

Question 1

what are the two types of ways that diuretics increase urine secretion

Answer 1

1. Natriuretic - thee ion transport system at different sites, which in turn
   reduces sodium reabsorption
2. Aquaretic - by working on the aquaporins and increasing the amount of solute-free water being
   excreted

Question 2

what are the 6 classes of diuretics

Answer 2

*Thiazide diuretics
*Loop diuretics
*Potassium-sparing diuretics
*Carbonic anhydrase inhibitors
*Osmotic diuretics
*Vasopressin receptor antagonists

Question 3

Approximately 20% of the blood plasma that enters the kidneys is filtered
through to _____________ and _______

Answer 3

Bowman’s capsule and nephron

Question 4

What are the 5 functional zones of nephron?

Answer 4

Proximal Convoluted Tubule
Descending Loop of Henle
Ascending Loop of Henle
Distal Convoluted Tubule
Collecting Tubule and Duct

Question 5

What generally happens in the proximal convoluted tubule?

Answer 5

Approximately 66% of filtered Na+, 85% of the
NaHCO3, 65% of the K+, 60% of the water, and
virtually all of the filtered glucose and amino acids
are reabsorbed in the proximal tubule

● Organic acid secretory systems are also located in
the proximal tubule

Note: Medications do not work on this part of the kidney.

Question 6

What generally happens in the descending loop of Henle?

Answer 6

Loop passes into the kidney’s medulla.
Water is extracted from the descending limb of

this loop by osmotic forces found in the
hypertonic medullary interstitium

Osmolarity increases, aka salt concentration increases by 3x.

Question 7

What generally happens in the ascending loop of Henle?

Answer 7

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.

Question 8

What generally happens in the distal convoluted tubule?

Answer 8

10% of filtered NaCl is reabsorbed via thiazide-sensitive Na/Cl co-transporter.

Ca reabsorbed via Na/Ca exchanger, which is regulated via parathyroid hormone.

Question 9

What generally happens in the collecting tubule?

Answer 9

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!!!!

Question 10

What cells does aldosterone work on in the kidneys?

Answer 10

Principal cells.

Question 11

What kind of transporter does the a principal cell have?

Answer 11

Na/K, generally pumping Na back into the blood, and K back into the urine.

Question 12

What happens if a diuretic increases Na+ delivery to the collecting duct?

Answer 12

More potassium shifts of out the blood, so your urine concentration of K is much higher.

Question 13

What are the water channels in principal cells called?

Answer 13

Aquaporins.

Question 14

What hormone regulates aquaporins?

Answer 14

ADH/Vasopressin.

Question 15

What does ADH do to an aquaporin?

Answer 15

Makes cells permeable to water, concentrating the urine.

Question 16

Where do loop diuretics work on in the kidney?

Answer 16

Ascending loop

Question 17

Why do we like loop diuretics?

Answer 17

They have the highest efficacy in diuretic effect, aka you take more, the more effect. They are sometimes known as high-ceiling diuretics.

Question 18

What are the 3 loop diuretics?

Answer 18

Furosemide (Lasix)
Torsemide
Bumetanide (Bumex)

Question 19

What is the MOA of a loop diuretic?

Answer 19

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 Excretion , but most Ca is reabsorbed later.

Can increase renal blood flow by increasing prostaglandin production.

Note: NSAIDs can reduce effect.

Question 20

What is the PK of a loop diuretic?

Answer 20

administration either orally or paraenterally

Rapid onset, even with renal insufficiency patients

duration of action = 2-8 hours, (lasix = six hours)

Secreted into urine via organic acid system.

The most potent is bumetanide, following by torsemide and then furosemide.

Question 21

What are the indications for a loop diuretic?

Answer 21

Reducing edema, both peripheral and central. (good in emergencies due to rapid onset)

Combined with hydration, it is good for managing hypercalcemia

Also can treat hyperkalemia.

Question 22

What are some contraindications for a loop diuretic?

Answer 22

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. (rare complication)

Hypovolemia, hypokalemia, hypomagnesemia.

Hyperuricemia (leads to high uric acid and can cause gout attacks

Pregnancy Category C (There are no satisfactory studies in pregnant women, but animal studies demonstrated a risk to the fetus; potential benefits of the drug may outweigh the risks.)

Question 23

What kind of patients should not a loop diuretic?

Answer 23

People on other ototoxic drugs like aminogylcosides.
People with gout or high uric acid levels.
Pregnant women