Lecture 5.2: Diuretics

Question 1

What is Diuresis?

Answer 1

Increased formation of urine by the kidney

Question 2

What are Diuretics?

Answer 2

Substances/Drugs that promote Diuresis

Question 3

What is a Mechanistic Overview of how Diuretics work?

Answer 3

• Increased renal excretion of water AND sodium
• Leads to a reduction of ECF volume

Question 4

Why are Diuretics used in Clinical Practice?

Answer 4

In conditions where Na⁺ and water retention cause expansion of ECF volume e.g. Heart Failure

Question 5

How to calculate Total Body Water (TBW)?

Answer 5

0.6 x body weight

Question 6

What makes up TBW? (2)

Answer 6

• Intracellular Fluid
• Extracellular Fluid

Question 7

How to calculate Intracellular Fluid (ICF)?

Answer 7

0.4 x bodyweight

Question 8

How to calculate Extracellular Fluid (ECF)?

Answer 8

0.2 x bodyweight

Question 9

What makes up the ECF? What percentages of the ECF do they make up? (2)

Answer 9

• Interstitial Fluid (ISF): 75%
• Plasma: 25%

Question 10

What is Natriuresis?

Answer 10

Increased sodium excretion

Question 11

What is Kaliuresis?

Answer 11

Increased potassium excretion

Question 12

What are Aquaretics? Example?

Answer 12

• A substance that causes net excretion of water
• Tolvaptan

Question 13

What Types of Diuretics affect the PCT and Proximal Straight Tubule? Examples?

Answer 13

• Carbonic Anhydrase Inhibitors
• Acetazolamide
• Cetazolamide
• Methazolamide

Question 14

What Types of Diuretics affect the Thin Descending & Ascending Loop of Henle? Examples?

Answer 14

• Osmotic Diuretics
• Mannitol

Question 15

What Types of Diuretics affect the Thick Ascending Limb of the Loop of Henle? Examples?

Answer 15

• Loop Diuretics
• Furosemide
• Bumetanide

Question 16

What Types of Diuretics affect the Distal Convoluted Tubule? Examples?

Answer 16

• Thiazide Diuretics
• Metolazone
• Indapamide
• Hydrochlorothiazide (HCTZ)

Question 17

What Types of Diuretics affect the Cortical Collecting Tubule? Examples?

Answer 17

• K+-sparing Diuretics/ Inhibitors of Renal Na+ Channels
• Amiloride
• Triamterene

Question 18

What Types of Diuretics affect the Collecting Tubule? Examples? (2)

Answer 18

• Na⁺ Channel Blockers: Amiloride
• Aldosterone Antagonists: Spironolactone

Question 19

Mechanism of Action: Carbonic Anhydrase Inhibitors (Acetazolamide)

Answer 19

• Inhibits action of carbonicanhydrase in brush border &PCT cell
• Can cause metabolic acidosis due to loss of HCO3 in urine

Question 20

What else are Carbonic Anhydrase Inhibitors used to treat?

Answer 20

• Useful in the treatment of Glaucoma
• Reduces formation of aqueous humour in the eye by about 50%

Question 21

Mechanism of Action: Osmotic Diuretics (Mannitol)

Answer 21

• Small inert molecules
• Increases plasma osmolarity thus drawing out fluid from tissues & cells (IV
mannitol used to treat cerebral oedema)
• Freely filtered at the glomerulus, but not reabsorbed
• Increases the osmolarity of the filtrate
• Acts by altering the driving force for renal water absorption, which is osmolarity
• Not inhibitors of enzymes or transport proteins
• Causes loss of water, Na⁺ and K⁺ in the urine

Question 22

Mechanism of Action: Loop Diuretics

Answer 22

• 30% of filtered Na⁺ absorbed via Na-K-2Cl transporter in LoH
• The K⁺ carried across apical membrane drifts back into lumen via K⁺ channels• • Creates a lumen positive potential
• Which helps to also to drive absorption of the positively charged ions Ca2+ and
Mg2+
• Loop diuretics block Na-K-2 Cl transporter

Question 23

Mechanism of Action: Thiazide Diuretics

Answer 23

• Block Na - Cl transporter in DCT
• Increases Na⁺ (and H2O) loss
• Reduces Ca loss in urine
• Less potent diuretics than loop diuretics
• Only 5% of sodium reabsorption inhibited
• Sodium reabsorbed via NaCl transporter

Question 24

What types of diuretics can produce life threatening Hyperkalaemia?

Answer 24

• K-Sparing Diuretics
• Aldosterone Antagonists

Question 25

Mechanism of Action: Aldosterone Antagonists (e.g.spironolactone)

Answer 25

• Antagonise the action of Aldosterone • Aldosterone acts on Principal cells of Late DT & CD • ↑ Na reabsorption via ENaC • Competitive inhibition of aldosterone receptor cause ↓ Na reabsorption

Question 26

What are 'Starling's Forces'?

Answer 26

Movement of fluid across capillary walls is essential for maintaining a continuous exchange of oxygen and carbon dioxide between the body's cells and the blood supply

Question 27

Formation of Tissue Fluid: Movement between Intravascular and Interstitial Spaces

Answer 27

1) Capillary Hydrostatic Pressure: pressure due to force of gravity on fluid in the capillary, pushing fluid out 2) Plasma Oncotic Pressure: osmotic pressure due to non-permeant molecules such as proteins in the plasma, drawing fluid in

Question 28

What is capillary hydrostatic pressure mainly influenced by?

Answer 28

Venous pressure in the systemic circulation

Question 29

Does fluid move out at the arteriole or venous end?

Answer 29

• Fluid tends to move out at arterial end • Moves in at the venous end

Question 30

What are some Conditions that cause ECF Expansion and Oedema? (4)

Answer 30

• Congestive Heart Failure • Nephrotic Syndrome • Cirrhosis of the Liver • Portal Hypertension

Question 31

What is Congestive Heart Failure?

Answer 31

Heart failure is where the heart is unable to pump blood around the body properly and needs treatment to help it work

Question 32

Why does Oedema build up in Congestive Heart Failure?

Answer 32

• ↑ systemic venous pressure → oedema • Drop in CO → activation of Renin-Angiotensin System (RAAS) → Na+ & water retention → expansion of ECF & oedema

Question 33

How do you treat Oedema build up in Congestive Heart Failure?

Answer 33

• Loop diuretics – e.g. furosemide or bumetanide are 1st choice therapy • Thiazide diuretics like metolazone are used as an adjunct

Question 34

What is Nephrotic Syndrome?

Answer 34

Nephrotic syndrome is a condition that causes the kidneys to leak large amounts of protein into the urine

Question 35

Why does Oedema build up in Nephrotic Syndrome?

Answer 35

Protein loss in urine → low plasma albumin → low oncotic pressure → oedema → reduced circulatory volume → RAS activated → Na & water retention → expansion of ECF & oedema

Question 36

How do you treat Oedema build up in Nephrotic Syndrome?

Answer 36

• Loop diuretics like furosemide or bumetanide are used • Thiazide diuretics like metolazone are used as an adjunct

Question 37

What is Cirrhosis of the Liver?

Answer 37

Cirrhosis is a late-stage liver disease in which healthy liver tissue is replaced with scar tissue and the liver is permanently damaged

Question 38

Why does Oedema build up in Cirrhosis of the Liver?

Answer 38

Cirrhosis of liver → less albumin production in liver → low plasma albumin → low oncotic pressure → oedema→ reduced circulatory volume → RAS activated → Na & water retention → expansion of ECF & worsening oedema

Question 39

How do you treat Oedema build up in Cirrhosis of the Liver?

Answer 39

• Spironolactone

Question 40

What is Portal Hypertension?

Answer 40

• Portal hypertension is elevated pressure in your portal venous system • The portal vein is a major vein that leads to the liver

Question 41

Why does Oedema build up in Portal Hypertension?

Answer 41

Portal hypertension → increased venous pressure in splanchnic circulation (high venous pressure + low oncotic pressure) → Ascites → reduced circulatory volume → RAS activated → Na & water retention → expansion of ECF & worsening oedema

Question 42

How do you treat Oedema build up in Portal Hypertension?

Answer 42

• Spironolactone

Question 43

What are some Adverse Effects of Diuretics? (7)

Answer 43

• Primarily Electrolyte Imbalances • Importantly Potassium Disturbances • Hypovolaemia • Hyponatraemia • ↑ Uric acid levels in blood • Metabolic Effects • Erectile Dysfunction (Thiazides)

Question 44

What Diuretics can cause Hypokalaemia?

Answer 44

• Loop and Thiazide Diuretics • Increase the loss of potassium in the urine may cause Hypokalaemia

Question 45

What Diuretics can cause Hyperkalaemia?

Answer 45

• K⁺ sparing Diuretics & Aldosterone Antagonists • Reduce excretion of potassium in the urine may cause Hyperkalaemia

Question 46

What are some substances with a diuretic effect?

Answer 46

• Alcohol – inhibits ADH release • Coffee − ↑GFR and ↓ tubular Na⁺ reabsorption • Other Drugs: Lithium, demeclocyline − inhibit ADH action on Collecting ducts

Question 47

What are some Diseases that cause Diuresis? (4)

Answer 47

• Diabetes Mellitus – glucose in filtrate - osmotic diuresis • Diabetes Insipidus (cranial) – ↓ADH release from post pituitary → diuresis • Diabetes Insipidus (nephrogenic) – Poor response of Collecting ducts to ADH → diuresis • Psychogenic polydipsia (Increased intake of fluid)