Diuretics Flashcards
Define diuretic
Substance or drug that promotes a diuresis by increased renal excretion of water and sodium to decrease extra cellular fluid volume
Define diuresis
Increased formation of urine by the kidney
What are the four main ways diuretics work?
Direct action on cells to block sodium transporters on the luminal membrane of the nephron
Antagonise action of aldosterone
Modify filtrate content
Inhibit carbonic anhydrase
Briefly, what does aldosterone do?
Acts on principal cells of the late DT and CD to increase expression of epithelial Na channels (ENaC)
Give an example of a loop diuretic
Furosemide
Bumetanide
What percentage of sodium is reabsorbed in the thick ascending limb?
25%
What normally happens in the thick ascending limb?
Na-K-2Cl does reabsorption
K+ drifts back into lumen -> positive lumen potential
Drives paracellular absorption of Ca2+ and Mg2+
How do loop diuretics work?
Secreted into PCT
Travel downstream to thick ascending limb
Block Na-K-2Cl transporter
Blocks ability to reabsorb sodium, potassium and chloride, and also calcium and magnesium
Segments downstream have limited capacity to reabsorb flood of Na+ and water
What are loop diuretics used for?
Heart failure due to vaso/venodilatation effect
Kidney failure
Acute pulmonary oedema caused by left heart failure
Hypercalcaemia
Fluid retention and oedema due to nephrotic syndrome or kidney failure
Where is the site of action of thiazide diuretics?
Distal convoluted tubule
Give an example of a thiazide diuretic
Bendroflumethiazide
Metolazone
What normally happens in the distal convoluted tubule?
Sodium-chloride transporter reabsorbs sodium and chloride
Calcium is reabsorbed and transported across basolateral membrane via NCX
3Na-2K-ATPase drives the whole thing
What is the action of thiazide diuretics?
Block the Na-Cl transporter in the DCT
Increases Na and water loss in urine
Increases calcium reabsorption (because there is a greater sodium gradient for NCX on basolat. because Na-Cl no longer working)
What are thiazide diuretics useful for treating?
Hypertension (causes vasodilation, not understood how)
Side effects of thiazide diuretics?
Hypokalaemia
Hypercalcaemia
Example of a potassium sparing diuretic?
Amiloride
Site of action of potassium soaring diuretics?
Collecting duct (principal cells)
What normally happens in the principal cells of the collecting duct?
Na+ reabsorbed via ENaC, takes water with it
Driven by Na-K-ATPase
K+ into cell via Na-K-ATPase on basolateral and secreted into lumen
Action of potassium sparing diuretics?
Directly block the ENaC in principal cells
Na no longer reabsorbed
Less of a gradient for Na-K-ATPase so less potassium is secreted
Action of aldosterone antagonists?
Block the action of aldosterone
Aldosterone normally increases expression of ENaC on apical membrane of principal cells
Less sodium reabsorption and less potassium secretion
Example of an aldosterone antagonist?
Spironolactone
Use of aldosterone antagonists?
Treat hypertension due to primary aldosteronism
Ascites and oedema in cirrhosis
In addition to loop diuretics in heart failure
What is Conn’s syndrome?
Adrenal hyperplasia or a tumour leading to increased aldosterone secretion. Causes hypertension
Uses of K+ sparing diuretics?
Often used with other diuretics eg thiazide to reduce hypokalaemia
When should K+ sparing diuretics and aldosterone antagonists not be used?
If patient is on ACE-inhibitors or K+ supplements
Patients with renal impairment
What does carbonic anhydrase do?
Does the reaction
HCO3- + H+ -> H2O + CO2
H2O and CO2 then absorbed into PCT cell and goes back to HCO3- by action of carbonic anhydrase
HCO3- can then be absorbed into the blood
Action of carbonic anhydrase inhibitors?
Inhibit carbonic anhydrase in the brush border and in PCT cells
Prevents reabsorption of HCO3
What can carbonic anhydrase inhibitors be useful to treat?
Glaucoma
Reduces formation of aqueous humour of the eye by 50%
Side effects of carbonic anhydrase inhibitors?
Metabolic acidosis because HCO3 is lost in the urine
How do osmotic diuretics work?
Small inert molecules which increase the plasma osmolarity
Causes fluid to be drawn out from rises and cells
They are freely filtered in the glomerulus but not reabsorbed to increase osmolarity of filtrate
Cause loss of H2O, Na+ and K+
Name an osmotic diuretic
Mannitol
What can osmotic diuretics be used to treat?
Cerebral oedema
IV mannitol
How does congestive heart failure lead to an expansion of ECF and oedema?
- drop in cardiac output
- RAAS activation
- Na and H2O retention
- expansion of ECF and oedema
- increase in systemic venous pressure
- oedema
How does nephrotic syndrome lead to an increase in ECF expansion?
- protein loss in urine
- decreased plasma albumin
- decreased oncotic pressure
- oedema
- reduced circulatory volume
- RAAS activation
- Na+ and H2O retention
- expansion of ECF
- oedema
How does cirrhosis of the liver lead to expansion of the ECF?
- decreased albumin production
- decreased plasma albumin
- decreased oncotic pressure
- oedema
- reduced circulatory volume
- RAAS activation
- Na and H2O retention
- expansion of ECF
- oedema
Which diuretics can cause hyperkalaemia?
Loop diuretics
Thiazide diuretics
Which diuretics can be used to treat hypokalaemia?
K+ sparing diuretics
Aldosterone antagonists
How do loop diuretics and thiazide diuretics cause hypokalaemia?
Block Na+ and H2O reabsorption in PCT
Increased Na+ and H2O to late DT and CD
Increased sodium absorption by principal cells
Favourable electrical gradient for K+ excretion
Faster flow rate in lumen so K+ excreted is washed away faster
More K+ lost in urine
In what other way do diuretics contribute to hypokalaemia?
Diuretics reduce ECF volume
Activation of RAAS
Aldosterone increases Na+ reabsorption and K+ excretion
Hypokalaemia
What is hepatic encephalopathy?
A reversible syndrome of impaired brain function which occurs in cirrhosis with advanced liver failure
Caused by elevated ammonia in the blood
What diseases can cause diuresis?
Diabetes mellitus
Diabetes insipidus (cranial or nephrogenic)
Psychogenic polydipsia
What is the difference between cranial and nephrogenic diabetes insipidus?
Cranial - less ADH released from posterior pituitary
Nephrogenic - poor response of collecting ducts to ADH
Both lead to diuresis
What are some adverse effects of diuretics?
Potassium abnormalities Hypovolaemia Hyponatraemia Increased uric acid in blood leading to gout (loop and thiazide) Metabolic effects (loop and thiazide) -glucose intolerance -raised LDLs Thiazides can cause erectile dysfunction
What does alcohol affect to cause a diuretic effect?
Inhibits ADH release
What does coffee do?
Increases GFR
Decreases tubular Na+ reabsorption
