Pathophysiology of Fluid Balance

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Questions and Answers

Which type of diuretic works by inhibiting the Na+/Cl- symporter in the distal tubule?

Thiazide diuretics (correct)

Carbonic anhydrase inhibitors

Loop diuretics

Aldosterone antagonists

What is the mechanism of action of thiazide-like analogs?

Increasing aquaporins

Inhibiting the Na+/Cl- symporter (correct)

Inhibiting the Na+/K+/2Cl- symporter

Decreasing the Na+/H+ antiporter

Which type of diuretic is used to treat hyperaldosteronism?

Thiazide diuretics

Loop diuretics

Aldosterone antagonists (correct)

Carbonic anhydrase inhibitors

What is the site of action of loop diuretics?

Ascending limb of the loop of Henle Signup and view all the answers

Which of the following diuretics is used to treat mountain sickness?

Acetazolamide Signup and view all the answers

What is the mechanism of action of carbonic anhydrase inhibitors?

Inhibiting the Na+/H+ antiporter Signup and view all the answers

What is the transporter associated with carbonic anhydrase inhibitors?

Na+/H+ antiporter Signup and view all the answers

Which type of diuretic is used to treat heart failure?

All of the above Signup and view all the answers

What is the site of action of aldosterone antagonists?

Collecting tubule Signup and view all the answers

What is the effect of aldosterone antagonists on aquaporins?

Decrease aquaporins Signup and view all the answers

In the kidney, what is the primary function of the proximal convoluted tubule?

Reabsorption of sodium ions Signup and view all the answers

What is the primary mechanism of action of loop diuretics?

Inhibition of the Na+/K+/2Cl- symporter Signup and view all the answers

What is the function of the collecting duct in the kidney?

Regulation of water reabsorption and potassium secretion Signup and view all the answers

What is the effect of aldosterone on the kidney?

Increases sodium reabsorption Signup and view all the answers

What is the primary site of action of thiazide diuretics?

Distal convoluted tubule Signup and view all the answers

What is the primary mechanism of action of aldosterone antagonists?

Inhibition of the epithelial sodium channel Signup and view all the answers

What is the primary effect of diuretics on the body?

Increased urine volume Signup and view all the answers

What is the primary cause of oedema?

Excessive sodium retention Signup and view all the answers

What is the primary function of aquaporins in the kidney?

Facilitate water reabsorption Signup and view all the answers

What is the primary site of action of osmotic diuretics?

Entire nephron Signup and view all the answers

What is the primary site of action for thiazide diuretics?

Distal convoluted tubule Signup and view all the answers

Which of the following diuretics increases the excretion of calcium?

Furosemide Signup and view all the answers

What is the mechanism of action of thiazide diuretics?

Inhibition of a Na+/Cl- cotransporter Signup and view all the answers

Which of the following is an aldosterone antagonist?

Spironolactone Signup and view all the answers

What is the effect of loop diuretics on the reabsorption of sodium in the nephron?

Decrease reabsorption in the ascending limb of Henle Signup and view all the answers

Which of the following diuretics is used to treat idiopathic hypercalciuria?

Hydrochlorothiazide Signup and view all the answers

What is the mechanism of action of aldosterone antagonists?

Inhibition of an aldosterone receptor Signup and view all the answers

Which of the following is a thiazide-like analog?

Indapamide Signup and view all the answers

Where does the inhibition of carbonic anhydrase occur in the nephron?

Proximal convoluted tubule Signup and view all the answers

What is the effect of loop diuretics on the reabsorption of potassium in the nephron?

Increase excretion in the distal convoluted tubule Signup and view all the answers

Study Notes

Causes of Oedema

Congestive heart failure: reduced ability of the heart to maintain cardiac output, leading to kidney response to hypovolaemic state to raise blood volume
Nephrotic syndrome: damaged glomerular membrane, loss of protein reduces colloidal osmotic pressure, leading to aldosterone secretion through RAAS
Hepatic cirrhosis: accumulation of fluid in the abdominal cavity
Premenstrual oedema: fluid retention due to hormonal changes

Treating Non-Oedematous States

Hypertension: reduce blood volume and dilate arterioles
Hypercalcaemia: promote calcium excretion, infused with normal saline due to hypovolemia
Diabetes insipidus: paradoxic treatment for polyuria and polydipsia, reduce plasma volume, decrease glomerular filtration rate, and increase sodium and water reabsorption

Classes of Diuretics

Carbonic anhydrase inhibitors: act on proximal convoluted tubule
Osmotic diuretics: act on descending limb of Henle and proximal convoluted tubule
Loop diuretics: act on ascending limb of Henle
Thiazide diuretics: act on distal convoluted tubule
Aldosterone antagonists: act on collecting ducts, potassium-sparing diuretics
ADH antagonists: act on collecting ducts

Carbonic Anhydrase Inhibitors

Mechanism of Action: inhibit carbonic anhydrase, preventing exchange of Na+ for H+, resulting in mild diuresis
Largely replaced by thiazides and loop diuretics
Indications: long-term use for oedema, chronic treatment of open-angle glaucoma, high altitude disorders prophylaxis
Adverse effects: metabolic acidosis, hypokalaemia, decreases uric acid secretion

Osmotic Diuretics

Mechanism of Action: increase osmolarity of tubular fluid, preventing water reabsorption
Regions affected: proximal tubule and descending limb of Henle
Indications: maintain urine flow in acute toxic ingestion, acute renal failure patients
Adverse effects: dehydration, headache

Loop Diuretics

Mechanism of Action: inhibit Na+/K+/2Cl- symporter, decreasing reabsorption of sodium, potassium, and chloride
Greatest diuretic effect of all diuretic drugs
Indications: acute pulmonary oedema and renal failure, hypertension, hypercalcaemia, hyperkalemia
Adverse effects: ototoxicity, hyperuricaemia, hypomagnesaemia, hypokalaemia, acute hypovolaemia

Thiazide Diuretics

Mechanism of Action: inhibit Na+/Cl- symporter, decreasing reabsorption of sodium and chloride
Indications: hypertension, mild congestive heart failure, idiopathic hypercalciuria, nephrogenic diabetes insipidus
Adverse effects: orthostatic hypotension, erectile dysfunction, hypokalaemia, hyponatraemia, hyperuricaemia, hypercalcaemia, hyperglycaemia

Thiazide-Like Analogs

Similar mechanism of action to thiazides
Indapamide: lipid-soluble, long duration of action, decreases blood pressure, low doses, minimal diuresis

Aldosterone Antagonists

Mechanism of Action: competitive antagonist of aldosterone, preventing sodium reabsorption and potassium secretion
Indications: hypertension, heart failure, secondary hyperaldosteronism
Adverse effects: hyperkalemia, gynaecomastia, menstrual irregularities, decreased libido, impotence

Potassium-Sparing Diuretics

Mechanism of Action: directly inhibit epithelial Na+ channels, decrease Na+/K+ exchange
Amiloride and triamterene: combinations with thiazides or loop diuretics, minimal diuresis
Side effects: leg cramps, decreased folic acid, contraindicated in pregnancy

ADH Antagonists

Mechanism of Action: decrease number of aquaporins, preventing water reabsorption
Indication: syndrome of inappropriate ADH secretion (SIADH)
Lithium and demeclocycline: non-selective, limited use

Ceiling Effects

Low ceiling diuretics: thiazides, increasing dose does not increase diuretic response
High ceiling diuretics: loop diuretics, increasing dose increases diuretic capability, substantial diuresis

Diuretic Tolerance and DDI

Short-term tolerance: decreased response after first dose, nephron primed to reabsorb sodium after drug levels decline
Long-term tolerance: gradual return of sodium chloride to electroneutral level, persistent volume removal triggers long-term RAAS activation
Diuretic resistance and DDI: NSAIDs, ACE-inhibitors, beta-blockers, K+ supplements, heparin, inadequate dosage, poor absorption, hypoalbuminuria, low cardiac output, and poor renal perfusion### Kidney Functions
Regulates ionic composition and urine volume through active reabsorption of water
Five functional zones of the nephron: proximal convoluted tubule, descending loop of Henle, ascending loop of Henle, distal convoluted tubule, and collecting duct
1.4 × 10^6 nephrons in each kidney
Functions include regulation of water and electrolyte content, retention of vital substances, maintenance of acid-base balance, excretion of waste products, and endocrine functions

Reabsorption

Where Na+ goes, H2O follows
Na+ leaves the tubule via active transport, anions follow Na+ across the electrochemical gradient
Water follows through diffusion from an area of low concentration to an area of high concentration (osmosis)
Low volume due to loss of water increases the concentration of K+ and other ions which follow if permeable to the membrane

Transporters

Symporters: transport protein binds more than one substance, facilitating transport across the membrane together (e.g., Na+/K+/2Cl- symporter, K+/Cl- symporter)
Uniporters: transport only one substance (e.g., renal medullary potassium channel (ROMK): ATP-dependent)
Antiporters: exchange one substance for another (e.g., Na+/H+ antiporter, Na+/K+ ATPase antiporter)

Proximal Convoluted Tubule

Kidney cortex
Passive flow: epithelium permeable to water and ions
Reabsorption of two-thirds of Na+, Na+/H+ antiporter, and Na+/K+ ATPase (basolateral membrane)
Carbonic anhydrase modulates bicarbonate reabsorption
Organic acid and base secretory systems

Loop of Henle

Descending limb: highly water permeable, paracellular transport, osmolarity increases along descending portion
Ascending limb: low permeability to water, active salt reabsorption via Na+/K+/2Cl- symporter, Na+/K+ ATPase in basolateral membrane

Distal Convoluted Tubule

Kidney cortex
Low permeability to water
Na+ and Cl- (10%) reabsorbed via Na+/Cl- symporter
Calcium reabsorption into interstitial fluid via Na+/Ca2+ exchanger

Collecting Ducts

Principal cells: sodium (ENaC), potassium (ROMK), and water transport, stimulated by aldosterone
Intercalated cells: α and β, acid-base homeostasis, hydrogen secretion
Sodium reabsorbed via Na+/K+ ATPase
Secretion of H+ and K+

Diuretics

Drugs that increase excretion of salt and water
Saluresis: urinary excretion of sodium and chloride ions
Treat oedematous and non-oedematous states
Most diuretics act on a single anatomical region of the nephron

Oedema

Rate of fluid formation exceeds that of reabsorption
Sodium chloride reabsorption is too high, resulting in water retention
Increased blood volume and expansion of extravascular fluid compartments

Classification of Diuretics

Carbonic anhydrase inhibitors (e.g., acetazolamide): act on proximal tubule, inhibit Na+/H+ antiporter
Osmotic diuretics (e.g., mannitol): act on proximal tubule and descending limb, freely permeable to water
Loop diuretics (e.g., furosemide): act on ascending limb, inhibit Na+/K+/2Cl- symporter
Thiazide diuretics (e.g., hydrochlorothiazide): act on distal tubule, inhibit Na+/Cl- symporter
Aldosterone antagonists (e.g., spironolactone): act on collecting tubule, inhibit ENaC

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Description

This quiz covers the pathophysiology of various conditions that affect fluid balance, including congestive heart failure, nephrotic syndrome, and others.