Diuretics Flashcards
Describe the general route of flow through he kidney
Bowman capsule Proximal tubule Descending loop of Henle Ascending loop of Henle (impermeable to water) Distal tubule Collecting duct
Explain sodium are reabsorbed from the proximal kidney tubules
Sodium transported through the apical membrane into the proximal tubule cell
The sodium potassium ATPase on the basal membrane ensures that sodium is reabsorbed into the blood very quickly, maintaining the concentration gradient.
Explain the movement of water through the proximal kidney tubules
Water can either move transcellularly (via aquaporins) or paracellularly
Transported through the apical membrane into the proximal tubule cell
In the lumen there is no protein. The oncotic pressure of proteins in the blood will draw water into the blood.
Explain how glucose and amino acids are reabsorbed from the kidney tubules
Sodium and hydrogen exchange at the apical membrane
Sodium here is coupled with glucose and amino acids to allow for their reabsorption
Explain how bicarbonate is reabsorbed from the kidney tubules
- Bicarbonate and H+ conversion to CO2 + H2O by carbonic anhydrase
- Transport into the tubule cell
- Conversion by carbonic anhydrase into H+ + HCO3-
- H+ exchanged with Sodium the apical membrane
- Bicarbonate transported through the basal membrane with sodium into the interstitium
Describe the excretion of drugs in the kidney
Excretion of drugs largely to take place in the proximal tubule. Recognition of groups e.g. glucuronide of drugs and excretion into the urine
Describe the transcellular transport occurring in the ascending loop of Henle
Impermeable to water - Sodium Chloride reabsorption
- Apical membrane protein allows movement of sodium, potassium and chloride
- Sodium exchanged with potassium at the basal membrane
- Potassium efflux back out at the basal membrane with chloride
Explain the countercurrent effect of the Loops of Henle
- The ascending limb is impermeable to water and sodium leaves to enter the medullary interstitium
- Decrease in ascending limb fluid osmolarity
- Water is drawn from the descending limb due to the concentration of medullary interstitial
- Fluid in the descending limb increases in osmolarity
- More fluid enters and forces fluid form descending to ascending limb
- This fluid is greater in osmolarity
The high osmolarity of the interstitium will allow for reabsorption of water from the collecting duct
Describe the transport of water through the distal tubule of the kidney
H20 enters the cell via AQP2
Enters intersititum via to AQP3/4
AQP synthesis stimulated by ADH binding to V2
Describe the transport of sodium through the distal tubule of the kidney
Early - Sodium chloride co-transport protein at the apical membrane -> sodium chloride reabsorption
Potassium levels balanced by symport with chloride at the basal membrane
Late - more permeable to water due to AQP
Describe the reabsorption of sodium in the collecting duct of the kidney
Sodium transport through a channel (apical)
Exchange with potassium
Potassium excreted into the tubule
Chloride enters from tubule -> interstitium
how do diuretics work
Inhibit the reabsorption of Na+ and Cl- (increase excretion)
Increase the osmolarity of tubular fliud (decreases the osmotic gradient across the epithelia)
What are the 5 main classes of diuretics and give an example of each
Osmotic diuretics - mannitol
Carbonic anhydrase inhibitors - acetazolamide
Loop diuretics - frusemide (furosemide)
Thiazides - bendrofluazide (bendroflumethiazide)
Potassium sparing diuretics - amiloride, spironolactone
Explain the mechanism of action of loop diuretics
Acts on the ascending loop of Henle, inhibiting the transport of sodium and chloride (30%)
There is an increase in tubular fluid osmolarity, while interstitium osmolarity decreases and water reabsorption from the collecting duct decreases
What are some other effects of loop diuretics
Increase in sodium delivery to the distal tubule
Increase in potassium loss
Calcium and magnesium reabsorbed- loss of potassium recycling
Explain the mechanism of action of thiazide diuretics
Inhibit sodium and chloride reabsorption in the early distal tubule (5-10%）
Increasing tubular fluid osmolarity and reducing water reabsorption in the collecting duct.
Less powerful than loop diuretics as there is a reduced effect on the interstitium
What are some other effects of thiazide diuretics
Increase in sodium delivery to distal tubule
Increase in potassium exchange
Magnesium loss
Calcium reabsorption
What is the problem with thiazide and loop diuretics
Long-term they activate the RAAS as they cause water and sodium loss. This is recognised by the macula densa cells.
This is a problem with loop diuretics as the protein that puts sodium into the macula densa cell is the one that is stopped by these loop diuretics so the macula densa cell activates RAAS
What are the classes of potassium sparing drugs and give an example of each
Aldosterone receptor antagonists
e.g. spironolactone
Inhibitors of aldosterone-sensitive Na+ channels
e.g. amiloride
Explain the mechanism of action of potassium sparing diuretics
Spironolactone causes a reduction in sodium channels and Na-K-ATPase and therefore less potassium loss due to inhibition of aldosterone receptors in the early distal tubule (5%)
Amiloride inhibits the entry of sodium
Reduced water reabsorption in collecting duct
What are some other effects of potassium sparing diuretics
reduction in reabsorption of Na+ to distal tubule
Increased H+ retention (reduced Na+/H+ exchange)
Give some common side effects of loop and thiazide diuretics
Hypovolaemia Metabolic alkalosis Hyponatraemia Hypokalaemia Hyperuricemia
What causes uric acid build up in the use of diuretics
The transport protein that moves diuretics across the basal membrane is the same that transports uric acid. With increased diuretic movement, less uric acid is excreted resulting in hyperuricemia
Give some common side effects of potassium sparing diuretics
Hyperkalaemia
What are the uses of diuretics
Thiazides are 1st line treatment of hypertension (salt sensitive)
Heart failure treatment
Why are thiazides used in hypertension treatment instead of other diuretics
Other diuretics Initial response (4-6 weeks) due to decreased plasma volume After 4=6 weeks - plasma volume restored
Chronic thiazides (in contrast with other diuretics) - causes vasodilation and reduces TPR
What is given along diuretics to inhibit the counter effect of RAAS
ACE inhibitors
Explain why diuretics can be used in heart failure treatment
The heart becomes less efficient at pumping blood so CO falls. RAAS and sympathetic system activation to increase blood pressure.
However, there is also cardiac remodelling which would input a greater load on the heart
There is also congestion of blood in the venous system
Diuretics would cause sodium reduction and fluid loss
What is the problem with using loop diuretics in heart failure and how is it overcome
Loop diuretics would cause sodium reduction and fluid loss, but it would also activate the RAAS.
To overcome this, a potassium sparing diuretic can be administered alongside.
