Flashcards in Renal Deck (42):
Where is 60-70% of NaCl reabsorbed?
The proximal tubule
How much NaCl is reabsorbed in the loop of henle?
Where is K+ reabsorbed and where is it secreted?
Reabsorbed in the proximal tubule and loop of henle (?)
Secreted in the Distal tubule and collecting ducts
Which section of the Nephron do loop diuretics act on?
Ascending loop of Henle
What ion channels do loop diuretics act on?
How do loop diuretics increase urine production?
By acting on the Na+/K+/2Cl- channel loop diuretics keep more ions in the lumen. Ordinarily the movement of ions into the epithelial cells and then into the interstitium creates an osmotic gradient which drives the movement of water into the interstitium which is reabsorbed. The lack of Osmotic pressure keeps water in the lumen and prevents water reabsorbtion. The increased osmotic pressure in the lumen reduces water reabsorbtion downstream as well, further increasing water secretion.
Name a common loop diuretic
What percentage of Na+ is excreted when furosemide is taken?
When are loop diuretics used?
Acute pulmonary oedema
Chronic heart failure
Ascites (liver failure)
How can loop diuretics cause hypokalaemia?
Decreased reabsorbtion of Na+ in the loop of henle
Increased concentration of Na+ in the distal tubule
Up-regulation of the Na+/K+ATPase pump in the dt = increased K+ secretion
What supplement is usually given with loop diuretics?
What is secreted when using a loop diuretic that may cause a metabolic alkalosis?
What is a potential negative outcome of furosemide in the elderly?
Loss of extracellular fluid volume causing hypovolaemia and hypotension
Where do thiazide diuretics act?
The distal convoluted tubule
What channels do thiazide diuretics act on?
The Na+/Cl- co-transporter
How do thiazide diuretics cause hypokaleamia?
As for loop diuretics except now the process occurs in the collecting duct
How long are loop diuretics active for?
Name 2 thiazide diuretics
How long are thiazides active for?
Max effect 4-6 hours but act for 8-12hours (they are excreted in the urine)
What are thiazides used for?
Severe resistant oedema (in combination with a loop diuretic)
Side effects of thiazides?
Increased uric acid due to inhibition of secretion - can cause gout
Hypokaleamia - co administered with a K+ supp
Name a thiazide like diuretic
Indapamide - reduced side effects
Name a potassium sparing diuretic
How do potassium sparing diuretics act?
The potassium-sparing diuretics are competitive antagonists that either compete with aldosterone for intracellular cytoplasmic receptor sites, or directly block sodium channels (specifically epithelial sodium channels (ENaC) by amiloride). The former prevents the production of proteins that are normally synthesized in reaction to aldosterone. These mediator proteins are not produced, and so stimulation of sodium-potassium exchange sites in the collection tubule does not occur. This prevents sodium re-absorption and potassium and hydrogen ion secretion.
What is the half life of spironolactone?
It is very short (about 10 minutes) buts its metabolite has a long half life (16 hours) and is still active
Is spironolactone fast or slow onset?
Slow onset long duration
When in spironolactone used?
In combination with a loop diuretic or thaizide diuretic
What are some side effects of potassium sparing diuretics?
What are triamterene and amiloride?
They are drugs which block epithelial sodium channels (stopping re-absorption) and hence block the secretion of potassium.
Describe the pharmacokinetics of Triamterene
Well absorbed, onset after 2 hours and works for a duration of 12-16 hours
Describe the pharmacokinetics of Amiloride
Poorly absorbed with a slow onset and a duration of action of about 24 hours
What are osmotic diuretics?
They are pharmocologically inert substances which are filtered but not reabsorbed. They act by changing osmolarity and hence reducing passive water reabsorbtion
Where do osmotic diuretics act?
They act the water permeable parts of the nephron (proximal tubule, descending loop of henle, collecting tubules)
When are osmotic diuretics used
Raised intra-cranial pressure
To prevent acute renal failure
- If GFR is so low/slow that all NaCl and water is being reabsorbed then water retention by osmotic diuretics is effective
These diuretics only have a small impact on Na+ retention
Name a heavy metal which damages the nephron
How does mercury damage the nephron
Direct toxicity and vasoconstriction
binds to the thiol groups in proteins and causes immune glomerulonephritis (inflammation either of the glomeruli or small blood vessels in the kidneys)
How can heavy metals damage the nephron?
Loss of brush boarder membranes
Cause mitochondrial changes
Name an antibiotic which can damage the kidney
How does gantamicin damage the nephron
Cationic drug binds to anionic phsopholipids
Altered generation of PIP2
Altered intracellular Ca2+ levels
Impaired mitochondrial respiration
This impairs secretion which in turn increases toxicity and thus generates a vicous cycle
Where does gentamicin act on the nephron?
Apical membrane of the proximal tubule
Describe how antineoplastic agents can damage the kidney:
These agents are activated inside cells
Form highly reactive species
Binds to the neucleophilic components of cell (eg thiols of proteins)