Renal Pharmacology

Question 1

What are the functions of the kidney?

Answer 1

Regulation of the extracellular fluid volume
Maintenance of ion balance 
Regulation of pH
Hormone secretion 
Excretion of foreign substances

Question 2

Briefly describe the journey of the nephron, giving the roles of each of the different parts of the nephron

Answer 2

1. Glomerulus - Site for ultrafiltration of blood
2. Proximal tubule - NaCl reabsorption, H+ secretion
3. Loop of Henlé and Vasa Recta - Countercurrent multiplier and exchanger concentrating systems
4. Distal tubule - Salt Reabsorption
5. Collecting tubules and collecting duct - Hormone-regulated H2O reabsorption and Na+ reabsorption

Question 3

In the glomerulus there are 4 processes that happen. What are they?

Answer 3

1. Filtration
2. Reabsorption
3. Secretion
4. Excretion

Question 4

Where is Renin released?

Answer 4

The juxtaglomerular apparatus (more specifically the granular cells)

Question 5

What is Renin a response to?

Answer 5

Over-excretion of Na+.

Question 6

Explain how to RAAS system affects blood pressure.

Answer 6

Angiotensinogen is released from the liver.
Renin released from the kidney converts Angiotensinogen to Angiotensin 1.
Angiotensin 1 is converted to Angiotensin 2 via ACE (Angiotensin Converting Enzyme).
Angiotensin 2 promotes vasoconstriction and therefore there is an INCREASE in blood pressure.

Question 7

In all sections of the nephron, there is tubular sodium reabsorption apart from ONE place. Where is it?

Answer 7

Descending limb of loop of Henlé

Question 8

The proximal convuluted tubule (PCT) accounts for 60-70% of the tubular sodium reabsorption. How does it do this?

Answer 8

In the luminal membrane:
Na+-H+ exchanger (H+ secretion)
Na+-coupled co-transporters (X = eg. glucose, amino acids etc)

The basolateral membrane:
Primary active transport by Na+-K+-ATPase
K+ efflux via renal K+ channels (this controls the balance of intracellular Na+)

Question 9

The thick ascending limb (TAL) of the loop of Henlé is responsible for around 25% of the tubular sodium reabsorption. How does it do this?

Answer 9

Luminal membrane:
Na+/K+/2Cl- co-transporter
Renal K+ channels

Basolateral membrane:
Na+-K+-ATPase
K+ Channels 
K+/Cl- co-transporter 
Cl- Channels

Question 10

The distal tubule only receives about 10% of the original volume of the glomerular filtrate, and accounts for 7% of tubular sodium reabsorption. How?

Answer 10

Luminal membrane:
Na+/Cl- co-transporter

Basolateral membrane:
Na+-K+-ATPase
K+ channels
K+/Cl- channels

Question 11

How does ADH (Anti-diuretic hormone) work in the collecting duct?

Answer 11

It acts to increase the expression of Aquaporin-2 in the luminal membrane. (Basically means drawing water out of the tubule back into the blood)

Question 12

How is Na+ reabsorption regulated in the collecting tubule?

Answer 12

Regulation via aldosterone.

Aldosterone increases the number of luminal Na+ channels and the number of basolateral Na+-K+-ATPases

Question 13

What natural hormone antagonises the effect of Aldosterone at the luminal Na+ channels?

Answer 13

Atrial Natriuretic Peptide (ANP)

Question 14

ANP is released in response to an increased preload in the heart by the heart. What are the actions of ANP in order to decrease the preload?

Answer 14

The adrenal gland decreases the amount of aldosterone secretion
The kidney decreases the amount of sodium reabsorption and renin secretion
Blood vessels dilate

These all cause an increase in diuresis and natriuresis which causes a decrease in blood volume

Question 15

How do water, ethanol, caffiene and nicotine affect diuresis?

Answer 15

Water, Ethanol and Caffiene all increase diuresis

However, nicotine decreases diuresis

Question 16

There are several types of diuretics and are classified by where they act on in the kidney. What are they and where do they act?

Answer 16

1. Loop diuretics - acts on the THICK ascending limb in the loop of Henlé
2. Thiazides - acts on the early distal tubule
3. K+ sparing diuretics - act on the collecting duct
4. Osmotic diuretics - act on the proximal tubule and THIN ascending limb
5. Carbonic Anhydrase Inhibitors - Act on proximal convoluted tubule

Question 17

What is the mechanism behind loop diuretics and what are the NET effects?

Answer 17

Mechanism: Inhibition of luminal Na+/K+/2Cl- transporter in the Thick Ascending Limb of the loop of Henlé
NET effects: decreased Na+ reabsorption
decreased Cl- reabsorption
Increased K+ loss

Question 18

What are the loop diuretics?

Answer 18

Furosemide

Bumetanide

Question 19

What is the mechanism behind thiazides and thiazide-like diuretics?

Answer 19

Mechanism: Inhibition of the luminal Na+/Cl- co-transporter in the early distal tubule

NET effects: decreased Na+ reabsorption
decreased Cl- reabsorption
MODERATE K+ secretion

Question 20

What are the thiazide drugs?

Answer 20

Thiazides:
Bendroflumethazide (most prescribed thiazide)
Chlorothiazide

Thiazide-likes:
Chlortalidone
Indapamide
Metolazone

Question 21

What are the ADRs of loop diuretics & thiazides?

Answer 21

Hypotension (due to hypovolaemia)
Gout (due to hyperuricaemia)
Hypokalaemia

Question 22

There are two types of potassium sparing diuretics: what are they?

Answer 22

Aldosterone antgaonists

Sodium Channel blockers

Question 23

Where do Potassium Sparing drugs act in the nephron?

Answer 23

Collecting tubule and collecting ducts

Question 24

What are the names of the potassium sparing diuretics?

Answer 24

Aldosterone Antagonists:
Spironolactone
Eplerenone

Na+ Channel blockers:
Amiloride
Triameterene

Question 25

What is the osmostic diuretic?

Answer 25

Mannitol

Question 26

What is the carbonic anhydrase inhibitor?

Answer 26

Acetazolamide