Renal Pharmacology Flashcards
What are the functions of the kidney?
Regulation of the extracellular fluid volume Maintenance of ion balance Regulation of pH Hormone secretion Excretion of foreign substances
Briefly describe the journey of the nephron, giving the roles of each of the different parts of the nephron
- Glomerulus - Site for ultrafiltration of blood
- Proximal tubule - NaCl reabsorption, H+ secretion
- Loop of Henlé and Vasa Recta - Countercurrent multiplier and exchanger concentrating systems
- Distal tubule - Salt Reabsorption
- Collecting tubules and collecting duct - Hormone-regulated H2O reabsorption and Na+ reabsorption
In the glomerulus there are 4 processes that happen. What are they?
- Filtration
- Reabsorption
- Secretion
- Excretion
Where is Renin released?
The juxtaglomerular apparatus (more specifically the granular cells)
What is Renin a response to?
Over-excretion of Na+.
Explain how to RAAS system affects blood pressure.
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.
In all sections of the nephron, there is tubular sodium reabsorption apart from ONE place. Where is it?
Descending limb of loop of Henlé
The proximal convuluted tubule (PCT) accounts for 60-70% of the tubular sodium reabsorption. How does it do this?
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+)
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?
Luminal membrane:
Na+/K+/2Cl- co-transporter
Renal K+ channels
Basolateral membrane: Na+-K+-ATPase K+ Channels K+/Cl- co-transporter Cl- Channels
The distal tubule only receives about 10% of the original volume of the glomerular filtrate, and accounts for 7% of tubular sodium reabsorption. How?
Luminal membrane:
Na+/Cl- co-transporter
Basolateral membrane:
Na+-K+-ATPase
K+ channels
K+/Cl- channels
How does ADH (Anti-diuretic hormone) work in the collecting duct?
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)
How is Na+ reabsorption regulated in the collecting tubule?
Regulation via aldosterone.
Aldosterone increases the number of luminal Na+ channels and the number of basolateral Na+-K+-ATPases
What natural hormone antagonises the effect of Aldosterone at the luminal Na+ channels?
Atrial Natriuretic Peptide (ANP)
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?
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
How do water, ethanol, caffiene and nicotine affect diuresis?
Water, Ethanol and Caffiene all increase diuresis
However, nicotine decreases diuresis
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?
- Loop diuretics - acts on the THICK ascending limb in the loop of Henlé
- Thiazides - acts on the early distal tubule
- K+ sparing diuretics - act on the collecting duct
- Osmotic diuretics - act on the proximal tubule and THIN ascending limb
- Carbonic Anhydrase Inhibitors - Act on proximal convoluted tubule
What is the mechanism behind loop diuretics and what are the NET effects?
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
What are the loop diuretics?
Furosemide
Bumetanide
What is the mechanism behind thiazides and thiazide-like diuretics?
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
What are the thiazide drugs?
Thiazides:
Bendroflumethazide (most prescribed thiazide)
Chlorothiazide
Thiazide-likes:
Chlortalidone
Indapamide
Metolazone
What are the ADRs of loop diuretics & thiazides?
Hypotension (due to hypovolaemia)
Gout (due to hyperuricaemia)
Hypokalaemia
There are two types of potassium sparing diuretics: what are they?
Aldosterone antgaonists
Sodium Channel blockers
Where do Potassium Sparing drugs act in the nephron?
Collecting tubule and collecting ducts
What are the names of the potassium sparing diuretics?
Aldosterone Antagonists:
Spironolactone
Eplerenone
Na+ Channel blockers:
Amiloride
Triameterene
What is the osmostic diuretic?
Mannitol
What is the carbonic anhydrase inhibitor?
Acetazolamide
