Renal Pharmacology & The Urinary System

Question 1

Which of the following stimulates sodium reabsorption by the kidneys?

a. atrial natriuretic peptide (ANP)
b. angiotensin
c. aldosterone
d. ADH

Answer 1

B, C, D

Question 2

Hypoalbuminemia can be caused by all of the following EXCEPT:

a. renal disease
b. hepatic disease
c. heart failure
d. malnutrition

Answer 2

C

Question 3

In cases of severe generalized edema, which of the following fluid compartments is increased in volume?

a. intracellular fluid (ICF)
b. interstitial fluid (IF)
c. transcellular water
d. plasma

Answer 3

B

Question 4

How much cardiac output does the kidneys receive?

Answer 4

20-25%

Question 5

What are 6 key functions of the kidneys?

Answer 5

1. ECF maintenance (sodium, water)
2. elimination of waste products
3. renal transport
4. autoregulation of renal blood flow (and systemic blood pressure) using RAAS, renin, tubular-glomerular feedback, and myogenic response
5. endocrine functions - EPO, calcitriol
6. acid-base balance

Question 6

How much of the total body water is extracellular fluid? What determines its volume? What systems control this?

Answer 6

~ 20%

total sodium content (major ion subject to active transport)

cardiovascular system, renal system (RAAS, diuresis), CNS (ADH release from the hypothalamus/pituitary, thirst)

Question 7

Where in the kidneys is sodium reabsorbed? How?

Answer 7

PT - 65%; apical Na-dependent symporters, Na/H antiporter; basolateral Na/K ATPase, Na/HCO3 symporter

TAL - 25%; apical NKCC symporter, paracellular; basolateral Na/K ATPase

DT - 5%; apical ENaC, Na/Cl symporter; basolateral Na/K ATPase

Question 8

How does the alteration of sodium reabsorption in the proximal tubule affect other ion reabsorption?

Answer 8

blocking NKCC will decrease sodium, chloride, and potassium reabsorption, resulting in a more positively charged interstitium compared to the lumen

• altered transepithelial potential decreases the paracellular movement of calcium and magnesium from the lumen into the interstitium
• this also results in high levels of sodium reaching the CD, making potassium move outside of the cell via channels into the lumen —> increased excretion = hypokalemia

Question 9

How does the endocrine system stimulate and inhibit sodium reabsorption into the interstitium?

Answer 9

STIMULATION - angiotensin II, aldosterone, ADH

INHIBITION - ANP, nitric oxide, endothelin-1

Question 10

What are the 3 systems that regulate renal blood flow?

Answer 10

1. macula densa tubuloglomerular feedback - autoregulation of hydrostatic blood pressure by sensing GFR and Na/Cl reabsorption and changing pressure accordingly
2. local myogenic response - blood flow regulation
3. systemic RAAS - blood flow regulation

Question 11

What 2 active transport mechanisms are present in the proximal tubule to secrete waste products and xenobiotics?

Answer 11

1. OAT - organic anion (OA-) transporter
2. OCT - organic cation (OC+) transporter

Question 12

When do we reduce ECF volume? How?

Answer 12

when fluid is inappropriately retained (edema), common in cardiac, renal, and liver disease, lymphatic obstruction, high hydrostatic pressure, low plasma oncotic pressure, and water/salt retention

promote renal excretion of sodium, which is followed by water (diuretics)

Question 13

What are the 5 main classifications of diuretics? How are they decided upon?

Answer 13

1. loop diuretics
2. carbonic anhydrase inhibitors
3. thiazides
4. osmotic diuretics
5. potassium-sparing diuretics

underlying disease (cause of ECF retention), mechanism/site of action of the drug, side effects

Question 14

What is the mechanism of action of diuretics?

Answer 14

inhibits NaCl reabsorption, which also decreases water reabsorption, which decreases ECF volume

Question 15

How do osmotic diuretics work? What are the 3 most common ones used?

Answer 15

increase the osmolality of ECF, enhancing the flow of water from tissues to the interstitial and intravascular fluids —> increased filtration rates with no target in the kidney

1. mannitol
2. glycerin
3. hypertonic saline

Question 16

What are the 3 pharmacokinetic properties of osmotic diuretics? What is their mechanism of action?

Answer 16

1. must be freely filtered
2. not reabsorbed
3. not metabolized

increased concentration of the osmotic diuretic in the tubular lumen causes less movement of water (and sodium) into the tubular cells, causing water to flow into the tubular lumen leaving with the urine

Question 17

How does mannitol work as an osmotic diuretic? How must it be administered?

Answer 17

does not enter the cells, but remains in the ECF allowing it to extract water from intracellular compartments and increase ECF volume while decreasing blood viscosity

no PO absorption —> must be IV

Question 18

What is mannitol? Where does it work best? What magnitude of sodium is lost?

Answer 18

sugar alcohol that acts throughout the nephron, especially stronger at the loop of Henle

sodium loss is small

Question 19

What are the 3 indications for mannitol usage? What is it not effective as?

Answer 19

1. oliguric renal failure
2. glaucoma - gets water out to decrease pressure
3. CNS edema - decreases brain mass/volume before cranial surgery

moving fluids from intracellular fluid - distributed to ECF

Question 20

What are 2 contraindications for mannitol usage?

Answer 20

1. anuria
2. cranial bleeding

Question 21

What do carbonic anhydrase inhibitors target? What does this cause?

Answer 21

both cytosolic and luminal (membrane-bound) CA at the proximal tubule, which blocks the breakdown of H2CO3 into CO2 that can be brought into the tubular cells and the synthesis of HCO3 from that CO2

hydrogen ions are not generated in the cell and not available for exchange with Na, resulting in reduced Na and HCO3 reabsorption —> loss in urine causes a reduced elimination of acids, increased pH of urine, and metabolic acidosis

Question 22

How can carbonic anhydrase inhibitors affect other parts of the kidney?

Answer 22

the sodium not absorbed will travel through the tubules and be reabsorbed at distal segents of the nephron at the expense of higher potassium elimination —> hypokalemia

Question 23

In what other 4 tissues is carbonic anhydrase found? What effect can the use of carbonic anhydrase inhibitors as diuretics have on these tissues?

Answer 23

1. aqueous humor and CSF - decreases formation, helpful for glaucoma (primary use)
2. gastric mucosa - reduces acid secretion
3. RBC - increases CO2 levels in peripheral tissues and reduced levels in exhaled air
4. macular densa - increases the amount of solutes delivered, activating TGF and decreasing GFR

Question 24

What is the main carbonic anhydrase inhibitor used? What is the primary indication? When is use contraindicated?

Answer 24

Acetazolamide

glaucoma

metabolic acidosis - reduces the elimination of weak acids by decreasing HCO3 filtering (low amounts of filtered HCO3 is absorbed by the uncatalyzed spontaneous hydration reaction, leading to refractoriness)

Question 25

How can carbonic anhydrase inhibitors be more effective?

Answer 25

when used in combination with loop diuretics or potassium-sparing diuretics

Question 26

How do thiazide diuretics work? What are the less effective at?

Answer 26

directly inhibit the Na/Cl co-transportation in the DT (saluretic)

causing Na excretion (most reabsorption occurs earlier by secondary active transport)

Question 27

What causes the variability of the duration of the diuretic effect of thiazide diuretics? What are 6 common side effects?

Answer 27

variable oral bioavailability, elimination half-life, and potency

1. volume depletion (increased Na and Cl elimination pulls water with them)
2. hypotension
3. hyponatremia
4. hypochloremia
5. hypomagnesemia (decreased Cl impairs paracellular Mg movement)
6. hypokalemia

Question 28

What drugs does thiazide diuretics decrease effectiveness? Increase effectiveness?

Answer 28

DECREASE: anticoagulants, uricosuric drugs, insulin

INCREASE: anesthetics, digitalis glycosides, lithium, vitamin D

Question 29

What is the main indication of thiazide diuretics? When is usage contraindicated?

Answer 29

early congestive heart failure

patients with impaired renal function (reduced GFR) and hypercalemia

Question 30

What are the 2 most common thiazide diuretics? What are each indicated for?

Answer 30

1. Chlorothiazide - diuretic, partial ADH deficiency/nephrogenic diabetes insipidus
2. Hydrochlorothiazide - diuretic, antihypertensive, nephrogenic diabetes insipidus, hypoglycemia