Diuretics Flashcards
What are diuretics?
Drugs that act on the renal tubule to promote the excretion of sodium, chloride and water.
Describe the arrangement of proximal tubule cells.
Tubular epithelial cells surround the lumen of the nephron.
On the basolateral side of the epithelial cells are capillaries passing through the kidneys.
How do sodium and water move across the proximal tubule epithelium?
A lot of sodium is reabsorbed in the proximal tubule.
On the apical side there are sodium channels that allow sodium to diffuse into the epithelial cell.
Water can follow sodium into the cell via osmosis.
Once sodium is in the epithelial cell, Na+/K+ ATPase pumps sodium out of the cell into the blood in exchange for K+.
The oncotic pressure exerted by the proteins in the blood in the capillaries exerts an important force in drawing water into the capillaries.
The paracellular pathway is dependent on the gap junctions between cells- the proximal tubule has large gap junctions between cells so there is a fair amount of movement of ions and water via the paracellular pathway in this region.
A lot of glucose and amino acids are also reabsorbed in the proximal tubule, and these tend to be coupled with sodium reabsorption.
Sodium exchange is linked to carbonic anhydrase:
CO2 + H2O -> HCO3- + H+
H+ and HCO3- are filtered by the glomerulus into the filtrate- this then interacts with membrane bound carbonic anhydrase, which converts it to CO2 + H2O.
CO2 and H2O can freely diffuse into the cell.
When in the cell, they are acted upon by carbonic anhydrase that converts them back to H+ and HCO3-.
HCO3- ions are then reabsorbed into the capillaries with sodium (Na+/HCO3- cotransport).
The H+ is used to drive the Na+/H+ exchanger at the apical membrane.
A lot fo sodium, bicarbonate and water reabsorption is the end result, most of which takes place in the proximal tubule.
What percentage of filtered fluid is reabsorbed in the proximal convoluted tubule?
65-70%
How does the kidney deal with exogenous agents?
The kidneys excrete a lot of drugs.
The drugs can be removed through transport proteins that pick up the drugs as they pass through the kidneys and transport them into the lumen.
Explain the countercurrent effect in the kidneys.
Descending limb- permeable to water.
Ascending limb- impermeable to water.
Sodium leaves the ascending limb and enters medullary interstitium.
Fluid in ascending limb decreases in osmolarity.
More concentrated medullary interstitium draws water from the permeable descending limb.
Fluid in descending limb increases in osmolarity.
More fluid enters and forces fluid from descending to ascending limb.
This fluid has increased in osmolarity due to increased sodium concentration in the medulla.
Sodium leaves the ascending limb and enters medullary interstitium.
Fluid in ascending limb decreases in osmolarity.
How do diuretics work?
Inhibit the reabsorption of sodium and chloride
i.e. increased excretion
Increase the osmolarity of tubular fluid
i.e. decrease the osmotic gradient across the epithelia
What are the main classes of diuretics? Give examples.
Osmotic diuretics, e.g. mannitol
Carbonic anhydrase inhibitors, e.g. acetazolamide
Loop diuretics, e.g. frusemide (furosemide)
Thiazides, e.g. bendrofluazide (bendroflumethiazide)
Potassium sparing diuretics, e.g. amiloride, spironolactone
What is the action of osmotic diuretics, e.g. mannitol, on sodium reabsorption?
None.
What is the action of osmotic diuretics, e.g. mannitol, on water reabsorption?
Increase the osmolarity of tubular fluid, therefore decreased water reabsorption where the nephron is permeable to water: proximal tubule, descending loop of Henle, collecting duct.
Where do carbonic anhydrase inhibitors, e.g. acetazolamide, act?
Proximal convoluted tubule.
What is the action of loop diuretics, e.g. frusemide, on sodium reabsorption?
Inhibit Na+ and HCO3- reabsorption in proximal tubule.
Inhibit Na+ and Cl- reabsorption in ascending limb- 30%.
What is the action of loop diuretics, e.g. frusemide, on water reabsorption?
Increased tubular fluid osmolarity
Decreased osmolarity of medullary interstitium
Decreased water reabsorption in the collecting duct
What are the other effects (apart from on sodium and water reabsorption) of loop diuretics, e.g. frusemide?
Increased delivery of HCO3- to distal tubule
Ca2+ and Mg2+- loss of potassium recycling
Increased delivery of Na+ to distal tubule
Increased K+ loss (increased sodium/potassium exchange)- in common with thiazides
What is potassium recycling?
Drives the positive lumen potential.
