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Urinary System > Lecture 5.2: Diuretics > Flashcards

Lecture 5.2: Diuretics Flashcards

1
Q

What is Diuresis?

A

Increased formation of urine by the kidney

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2
Q

What are Diuretics?

A

Substances/Drugs that promote Diuresis

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3
Q

What is a Mechanistic Overview of how Diuretics work?

A

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

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4
Q

Why are Diuretics used in Clinical Practice?

A

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

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5
Q

How to calculate Total Body Water (TBW)?

A

0.6 x body weight

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6
Q

What makes up TBW? (2)

A

• Intracellular Fluid
• Extracellular Fluid

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7
Q

How to calculate Intracellular Fluid (ICF)?

A

0.4 x bodyweight

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8
Q

How to calculate Extracellular Fluid (ECF)?

A

0.2 x bodyweight

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9
Q

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

A

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

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10
Q

What is Natriuresis?

A

Increased sodium excretion

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11
Q

What is Kaliuresis?

A

Increased potassium excretion

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12
Q

What are Aquaretics? Example?

A

• A substance that causes net excretion of water
• Tolvaptan

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13
Q

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

A

• Carbonic Anhydrase Inhibitors
• Acetazolamide
• Cetazolamide
• Methazolamide

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14
Q

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

A

• Osmotic Diuretics
• Mannitol

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15
Q

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

A

• Loop Diuretics
• Furosemide
• Bumetanide

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16
Q

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

A

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

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17
Q

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

A

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

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18
Q

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

A

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

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19
Q

Mechanism of Action: Carbonic Anhydrase Inhibitors (Acetazolamide)

A

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

20
Q

What else are Carbonic Anhydrase Inhibitors used to treat?

A

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

21
Q

Mechanism of Action: Osmotic Diuretics (Mannitol)

A

• 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

22
Q

Mechanism of Action: Loop Diuretics

A

• 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

23
Q

Mechanism of Action: Thiazide Diuretics

A

• 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

24
Q

What types of diuretics can produce life threatening Hyperkalaemia?

A

• K-Sparing Diuretics
• Aldosterone Antagonists

25
Q

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

A

• 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

26
Q

What are ‘Starling’s Forces’?

A

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

27
Q

Formation of Tissue Fluid: Movement between Intravascular and Interstitial Spaces

A

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

28
Q

What is capillary hydrostatic pressure mainly influenced by?

A

Venous pressure in the systemic circulation

29
Q

Does fluid move out at the arteriole or venous end?

A

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

30
Q

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

A

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

31
Q

What is Congestive Heart Failure?

A

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

32
Q

Why does Oedema build up in Congestive Heart Failure?

A

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

33
Q

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

A

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

34
Q

What is Nephrotic Syndrome?

A

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

35
Q

Why does Oedema build up in Nephrotic Syndrome?

A

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

36
Q

How do you treat Oedema build up in Nephrotic Syndrome?

A

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

37
Q

What is Cirrhosis of the Liver?

A

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

38
Q

Why does Oedema build up in Cirrhosis of the Liver?

A

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

39
Q

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

A

• Spironolactone

40
Q

What is Portal Hypertension?

A

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

41
Q

Why does Oedema build up in Portal Hypertension?

A

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

42
Q

How do you treat Oedema build up in Portal Hypertension?

A

• Spironolactone

43
Q

What are some Adverse Effects of Diuretics? (7)

A

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

44
Q

What Diuretics can cause Hypokalaemia?

A

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

45
Q

What Diuretics can cause Hyperkalaemia?

A

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

46
Q

What are some substances with a diuretic effect?

A

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

47
Q

What are some Diseases that cause Diuresis? (4)

A

• 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)

Urinary System (15 decks)

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