Diuretics Flashcards
What is diuresis?
Increased formation of urine by the kidney
How do diuretics generally act?
By blocking reabsorption of sodium and water by the tubule, blocking the action of aldosterone, modifying filtrate content or inhibiting the activity of carbonic anhydrase
What channel pumps Na+ out across the basolateral membrane of the tubule?
Na-K-ATPase
True or False:
Na+ moves across the apical membrane of tubules against its concentration gradient
False
Moves down its concentration gradient - set up by Na/K pump on basolateral membrane that pumps sodium out of the cell - therefore tubular cell concentration of sodium is low
True or False:
The Na/K pump on the basolateral membrane is common to all segments of the tubule
True
What sodium channels are present in the apical membrane of the proximal tubule?
Na-H antiporter
Na-Glucose
Na-AA etc
What sodium channels are present in the apical membrane of the loop of henle?
NKCC (Na K 2 Cl)
What sodium channels are present in the apical membrane of the early distal tubule?
NaCl symporter
What sodium channels are present in the apical membrane of the late distal tubule and collecting duct?
ENaC
What do diuretics reducing ENaC activity also reduce?
K+ secretion
In which part of the kidney is there a net secretion of K+?
Principal cells in late DT and CD
K+ brought into cell on the basolateral membrane via Na/K pump and leaves via a K+ channel on the apical membrane
Does Na+ absorption favour K+ excretion in the principal cells?
Yes
Where do loop diuretics act?
Loop of henle
What do loop diuretics block?
NaKCC
Where do thiazide diuretics act?
Early DT
What do thiazide diuretics block?
Na-Cl cotransporter
What do K+ sparing diuretics act on?
Late DT and CD
Block ENaC
How does aldosterone act on principal cells of the late DT and CD?
Increases Na+ reabsorption via ENaC
How do aldosterone antagonists decrease Na reabsorption?
Competitive inhibition of aldosterone receptor - so aldosterone cannot increase reabsorption
How do osmotic diuretics work?
Increase osmolarity of filtrate - reduce water and Na+ reabsorption throughout the tubule
What are some examples of loop diuretics?
Furosemide, bumetanide
What is used in acute pulmonary oedema?
IV Furosemide (loop diuretic)
Why are loop diuretics used in heart failure?
For treatment of symptoms (breathlessness, oedema)
- Diuretic effect
- Vaso and venodilation
When are loop diuretics used to treat fluid retention and oedema?
In nephrotic syndrome, renal failure, cirrhosis of liveer
Why are loop diuretics useful in treatment of hypercalcaemia?
Impairs calcium absorption in loop of henle, increases urinary excretion of calcium
What effect does thiazide diuretics have calcium absorption?
Increases Ca2+ absorption - reduces Ca2+ loss in urine
What is an example of a thiazide diuretic?
Bendroflumethiazide
True or False:
Aldosterone antagonists are shown to reduce mortality in HF
True
Used in lon term tretment of HF (non diuretic effect)
What is the preferred drug for ascites and oedema in cirrhosis?
Aldosterone antagonists (eg spironolactone)
What is used to treat hypertension due to primary hyperaldosteronism (Conns syndrome)?
Aldosterone antagonist - spironolactone
Adrenal hyperplasia/tumour -> causes increased secretion of aldosterone -> hypertension
What does amiloride block?
ENaC
Why are ENaC blockers usually used in combination with loop or thiazide diuretics?
ENaC blockers have a K+ sparing effect
Used to minimise K+ loss
What does the rate of K+ secretion in the DT and CD depend on?
Concentration gradien across apical membrane and rate of sodium abdorption (inward movement of Na+ creates a favourable lumen negative potential for K+ secretion)
How can loop and thiazide diuretics lead to hypokalaemia?
Block Na+ reabsorption in LoH or early DT
Increased Na absorption by principal cells
Favourable electrical gradient for K+ excretion
More K+ loss in urine leading to hypokalaemia
Which diuretics are K+ sparing?
ENaC blockers and aldoserone antagonists
Why should spironolactone not be used along with K+ supplements?
Increased risk of hyperkalaemia as spironalactone is an aldosterone antagonist which is K+ sparing
How can glomerular disease lead to oedema?
Increase in GBM permeability to protein - proteins filtered and lost in urine
Causes low plasma albumin, resulting in a low plasma oncotic pressure -> peripheral oedema
Reduced circulatory volume -> RAAS activates
What conditions are diuretics used in?
Conditions with ECF expansion and oedema
(Congestive HF, nephrotic syndrome, cirrhosis, kidney failure)
Acute pulmonary oedema
HF
Hypertension
What are some adverse effects of diuretics?
Potassium abnormalities Hypovolaemia Hyponatraemia Increased uric acid levels -> gout attacks Erectile dysfunction (thiazides) Gynaecomastia (spironolactone)
What is an example of a carbonic anhydrase inhibitor?
Acetazolamide
Where do carbonic anhydrase inhibitors act?
Proximal tubule - inhibits action of carbonic anhydrase in brush border + PCT cell
What is an example of an osmotic diuretic?
Mannitol
What is IV mannitol used to treat?
Cerebral oedema
What are some diseases that cause diuresis?
Diabetes mellitus
Diabetes insipidus
Psychogenic polydipsia
What are the two types of diabetes insipidus?
Cranial - decreased ADH release from post pituitary
Nephrogenic - poor response of CD to ADH
