Lecture 10-Diuretics Flashcards
What is a diuretic?
A substance that promotes increased urine by kidney by increasing renal excretion of water and Na+ -> decreased ECF volume
What are the broad ways in which diuretics work?
- direct action on cells to block Na+ absorption
- antagonising action of aldosterone
- modification of filtrate content (osmotic diuretics)
- inhibiting activity of carbonic anydrase enzyme in PCT to interfere with Na+ and HCO3- reabsorption
What do loop diuretics do?
Block apical NKCC2 in thick ascending limb of loop of Henle so less water reabsorbed later on -> Na+ and water loss
What helps to drive absorption of Ca2+ and Mg2+?
K+ channels on apical membrane bring K+ in and creates positive lumen potential
Give examples of loop diuretics
Furosemide
Bumetanide
When are loop diuretics used?
- Heart failure for treatment of symptoms (breathlessness and oedema)
- nephrotic syndrome
- renal failure
- liver cirrhosis (spironolactone preferred)
How can loop diuretics be used to treat hypercalcaemia?
Impairs Ca2+ absorption in loop of Henle and increases urinary excretion of Ca2+
What do thiazide diuretics do?
Block Na-Cl transporter in DCT
What are thiazide diuretics used to treat?
Hypertension
True or false: blocking Na+ in DCT increases Ca2+ absorption and decreases Ca2+ loss in urine
TRUE
Where do potassium sparing diuretics act?
Late DCT and CD on ENaC channels
What are the two types of potassium sparing diuretics?
- ENaC inhibitors (amiloride)
- aldosterone antagonists (spironolactone)
True or false: aldosterone antagonists reduce mortality in heart failure
TRUE
How can potassium loss be minimised?
Using potassium sparing diuretics with potassium losing diuretics
What can aldosterone antagonists be used to treat?
- heart failure
- ascites and oedema in cirrhosis
- hypertension due to primary hyperaldosteronism
What does the rate of potassium secretion in the DCT and CD depend on?
- conc gradient across apical membrane
- rate of Na+ absorption as inward movement of Na+ creates a negative lumen potential for K+ secretion
How can loop and thiazide diuretics lead to hypokalaemia?
1) block Na+ and water reabsorption in LoH and DCT -> increased Na+ and water to late DCT and CD -> increased Na+ absorption by principal cells -> gradient for K+ excretion -> hypokalaemia
2) block Na+ and water reabsorption in LoH and DCT -> increased Na+ and water to late DCT and CD -> faster flow of filtrate in lumen -> K+ in lumen washed away faster -> favourable conc gradient for K+ secretion -> hypokalaemia
How can ENaC inhibitors lead to hyperkalaemia?
Block ENaC -> decreased Na+ reabsorption -> decreased K+ loss in urine -> hyperkalaemia
How can aldosterone antagonists lead to hyperkalaemia?
Block aldosterone action -> reduce Na/K ATPase and ENaC activity -> decreased Na+ reabsorption -> decreased K+ loss in urine -> hyperkalaemia
When are diuretics used?
To treat conditions with ECF expansion and oedema
How does congestive heart failure lead to ECF expansion?
Decreased CO with decreased renal perfusion or increased systemic venous pressure -> oedema -> RAAS activation -> Na+ and water retention -> ECF expansion
How does nephrotic syndrome lead to ECF expansion?
Increased glomerular basement membrane permeability to protein -> proteinuria -> decreased plasma albumin -> decreased plasma oncotic pressure -> peripheral oedema -> decreased circulating volume -> RAAS -> Na and water retention -> ECF expansion
What are the adverse effects of diuretics?
- K+ abnormalities
- hyponatraemia
- dehydration
- increased uric acid -> gout
- glucose intolerance
- erectile dysfunction with thiazides
- breast enlargement with spironolactone
How do carbonic anhydrase inhibitors work?
Act on PCT to inhibit CA action in brush border and PCT
What are carbonic anyhdrase inhibitors used to treat?
Glaucoma as it decreases formation of aqueous humour
How can carbonic anhydrase inhibitors cause metabolic acidosis?
Loss of HCO3- in urine
How do osmotic diuretics work?
Small inert molecules which increase plasma osmolarity and draw fluid out from tissues and cells
Give an example of an osmotic diuretic
Mannitol
Which day-to-day substances have a diuretic effect?
- alcohol
- Coffee
Which diseases cause diuresis?
- diabetes mellitus
- diabetes insipidus: cranial or nephrogenic
- psychogenic polydipsia
What is the difference between cranial and nephrogenic diabetes insipidus?
- cranial: decreased ADH from posterior pituitary
- nephrogenic: poor response of CD to ADH
