Diuretics

Question 1

Define diuresis (1)

Answer 1

The increased formation of urine by the kidney.

Question 2

Define diuretics (2)

Answer 2

A class of drugs that act to cause a diuresis by increasing renal excretion of Na+ and water.

Question 3

Describe the different Na+ channels in the different parts of the nephron. (5)

Answer 3

PCT - NaH antiporter, Na-glucose or Na-AA symporters.
LoH - NKCC2 symporter
DCT - Na-Cl symporter
Late DCT and CD - ENaC

Question 4

Describe the action and use of loop diuretics. (7)

Answer 4

NKCC2 in the LoH blocked, Na+ and Cl- not reabsorbed so medulla not as concentrated so less water is reabsorbed later. This also blocks the formation of the positive lumen potential created by K+ diffusing back into the filtrate because Cl- still exists in the lumen, meaning Ca2+ and Mg2+ are not reabsorbed.
Used in treating heart failure (will reduce fluid overload but not change mortality), and fluid retention in cirrhosis, renal failure, nephrotic syndrome, and used in hypercalcaemia.

Question 5

Describe the action and use of Thiazide diuretics. (4)

Answer 5

Secreted into the lumen at PCT and travels with filtrate till it blocks Na-Cl symporter in DCT. Blocks Na+ reabsorption, which increases Ca2+ reabsorption.
Widely used in hypertension.

Question 6

Explain how Loop and thiazide diuretics can cause hypokalaemia. (9)

Answer 6

K+ secretion in DCT and CD is a passive process that depends on concentration gradient across apical membrane and rate of Na+ absorption. Blocked Na+ and H2O resorption leads to increased delivery to DCT&CD. This has 2 mechanisms that lead to hypokalaemia:

1. Increase Na+ reabsorption by principle cells leads to an electrical gradient for K+ secretion.
2. Faster flow rate washed K+ in the filtrate away creating a chemical gradient for K+ secretion.

Diuretics May also lead to low volume states which activates RAAS, where aldosterone release causes retention of Na+ and K+ secretion leading to hypokalaemia.

Question 7

Describe the two types of potassium sparing diuretic. (3)

Answer 7

Aldosterone agonists eg spirolactone - replaces aldosterone in stimulating ENaC, so indirectly acts to reduce ENaC action.
ENaC blockers - directly blocks ENaC.

Question 8

Describe the uses of the two types of K+ sparing diuretics (4)

Answer 8

Aldosterone agonists - reduced mortality in heart failure; used to treat hypertension not controlled by A or C, and hypertension secondary to hyperaldosteronism (Conn’s syndrome or adrenal tumour).
ENaC blockers - usually used in conjunction with K+ losing diuretics to reduce K+ loss.

Question 9

Describe the formation of hyperkalaemia in K+ sparing diuretics. (2)

Answer 9

Reduced ENaC action leads to reduced Na+ reabsorption, leads to reduced K+ loss in urine, leads to hyperkalaemia.

Question 10

Explain why diuretics are useful in treating congestive heart failure. (4)

Answer 10

CO reduced - Renal blood flow reduced - increase in systemic venous pressure - oedema - activation of RAAS due to reduced renal flow - Na+ and H2O retention - expansion of ECF - more oedema.
Diuretics can stop the aldosterone action or prevent Na+ reabsorption.

Question 11

Explain why diuretics might be needed in nephrotic syndrome. (5)

Answer 11

++ proteinuria - low plasma albumin - peripheral oedema - low circulating volume - RAAS - Na+ and H2O retention - more oedema. Diuretics can stop the aldosterone action or prevent Na+ reabsorption.

Question 12

Explain why diuretics might be needed in liver cirrhosis. (6)

Answer 12

Reduced albumin synthesis in the liver - low plasma albumin - low oncotic pressure - oedema.
Portal hypertension - high venous pressure and low oncotic pressure - ascites.
Both lead to reduced circulating volume - RAAS - Na+ and H2O retention.

Question 13

Describe some adverse effects that can result from diuretic use. (6)

Answer 13

Hypo- or hyperkalaemia.
Hypovolaemia
Hyponatraemia (in K+ sparing)
Increased uric acid (thiazide and loop) leading to gout flare ups.
Metabolic effects (thiazide and loop) - raised LDL, glucose intolerance.
Erectile dysfunction (thiazides)

Question 14

Explain 3 natural diuretics. (3)

Answer 14

Alcohol - limits ADH release.
Coffee - increases GFR and decreases Na+ reabsorption
Lithium - inhibits ADH.

Question 15

Explain 4 diseases that can cause diuresis. (4)

Answer 15

Diabetes mellitus - osmotic diuresis from glucose in urine.
Crainial diabetes insipidus - decreases ADH release from posterior pituitary reduced water reabsorption.
Nephrogenic diabetes insipidus - decreased sensitivity to ADH of collecting duct.
Psychogenic polydipsia.