Regulation of Water Balance

Question 1

What is osmolarity?

Answer 1

• The concentration of osmotically active particles in solution, which maybe quantitatively expressed is osmoles of solute per litre of solution

Osmolarity (Osm/L OR mOsm/L) = Concentration x No. of dissociated particles

Question 2

What does osmolarity depend upon?

Answer 2

• On the intrinsic property of the substance and dissociation capacity
  
  • ​Ionic compounds have the ability to dissociate into respective ions

Question 3

What are the 2 compartments of fluid in the human body?

Answer 3

• Intracellular fluid (2/3)
• Extracellular fluid (1/3)

Question 4

How is extracellular fluid divided?

Answer 4

• 3/4 Extravascular
• 1/4 Intravascular

Question 5

What is transcellular fluid?

Answer 5

• Refers to fluid that resides within epithelial lined spaces (cerebrospinal fluid and peritoneal fluid)

Question 6

What are 4 forms of unregulated water loss?

Answer 6

• Sweat
• Faeces
• Vomit
• Water evaporation from respiratory lining and skin

Question 7

What is the form of regulated water loss?

Answer 7

• Renal regulation - urine production

Question 8

What happens in a positive water balance?

Answer 8

High water intake → Increase ECF volume / Decrease [Na⁺] → Decrease osmolarity → Hypoosmotic urine production

Question 9

What happens in a negative water balance?

Answer 9

Low water intake → Decrease ECF volume / Increase [Na⁺] → Increase osmolarity → Hyperosmotic urine production

Question 10

Which transporters allow urea into the thin descending limb of the loop of Henle?

Answer 10

UT-A2

Question 11

Which urea transporters are located on the apical cell surface membrane of the collecting duct, allowing the passage of urea into the tubule cells?

Answer 11

UT-A1

Question 12

What is the UT-A3 transporter?

Answer 12

• Present on the basolateral cell membrane of the collecting duct, facilitating the passage of urea from the tubule cells into the medullary interstitium

Question 13

How is urea reabsorbed into the vasa recta?

Answer 13

• Via UT-B1 transporters

Question 14

What effect does vasopressin have on urea transporter?

Answer 14

• Vasopressin up-regulates UT-A1 and UT-A3, potentiating the increase of urea transport into the medullary interstitial fluid

Question 15

What impact does urea have on the osmolarity of the interstitial fluid?

Answer 15

• Increases the osmolarity by a significant magnitude

Question 16

Which hormone influences the permeability of the collecting duct to urea?

Answer 16

• Vasopressin / Antidiuretic Hormone / ADH

Question 17

How many amino-acids long is vasopressin?

Answer 17

• 9 amino acids

Question 18

What is the main function of vasopressin?

Answer 18

• Promotes water reabsorption from the DCT and collecting duct

Question 19

Which neurones synthesise vasopressin?

Answer 19

• Hypothalamic magnocellular neurones originating from the supraoptic and paraventricular nuclei

• Produced in the Hypothalamus
• Stores in the Posterior Pituitary

Question 20

What factors stimulate ADH production (5)?

Answer 20

• Increase in plasma osmolarity
• Hypovolaemia, decreased blood pressure
• Nausea
• Angiotensin II
• Nicotine

Question 21

What factor inhibit ADH production (4)?

Answer 21

• Decreased plasma osmolarity
• Hypervolaemia, increased blood pressure
• Ethanol
• Atrial natriuretic hormone (ANP)

Question 22

What is the normal plasma osmolarity in a healthy adult?

Answer 22

• 275-290 mOSm/kg

Fluctuation detected by osmoreceptors in hypothalamus

Question 23

What % range change in osmolarity is required for the detection of baroreceptors?

Answer 23

• 5-10%

Question 24

What is the mechanism of action of ADH (5)?

Answer 24

1. ADH binds to V2 receptor in basolateral membrane of the principal cell
2. Binding to V2 activates G protein mediated signalling cascade
3. Activates adenylate cyclase: ATP -> cAMP -> PKA -> increases secretion of AQP2
4. AQP2 transported to apical membrane
5. H₂O flows through AQP3 or AQP4 into blood

Question 25

What happens upon AVP binding to G-protein linked V2 receptors within principal tubule cells (2 steps)?

Answer 25

* **Activates adenylate cyclase activity**, generating cAMP. Protein kinase promotes the **migration of AQP 2 molecules** towards the basolateral membrane

Question 26

Which receptors does AVP bind to on tubule cells?

Answer 26

* **G-protein linked V2 receptors** on the basolateral cell surface membrane of principal tubule cells of the collecting duct

Question 27

What is diuresis?

Answer 27

* Diluted urine in high volume excretion

Question 28

What is the amount of ADH in diuresis?

Answer 28

Low to Zero

Question 29

How does the: Thick ascending limb / Distal convoluted tubule / Collecting duct change in diuresis?

Answer 29

* **Thick ascending limb:** Inhibit Na⁺ / K⁺ / 2Cl^- symporter * **Distal convoluted tubule:** Inhibit Na⁺ / Cl^- symporter * **Collecting duct:** Inhibit Na⁺ channel

Question 30

What is antidiuresis?

Answer 30

* Concentrated urine in low volume excretion

Question 31

What is the ADH amount in antidiuresis?

Answer 31

High

Question 32

How does the: Thick ascending limb / Distal convoluted tubule / Collecting duct change in antidiuresis?

Answer 32

* **Thick ascending limb:** Stimulate Na⁺ / K⁺ / 2Cl^- symporter * **Distal convoluted tubule:** Stimulate Na⁺ / Cl^- symporter * **Collecting duct:** Stimulate Na⁺ channel

Question 33

Which channels are integrated within the descending limb to facilitating water leaving the loop of henle and entering into the hyperosmolar interstititum?

Answer 33

* **Aquaporin channels**

Question 34

Describe the permeability to water in the ascending limb.

Answer 34

* **Impermeable** to water due to the absence of aquaporin channels

Question 35

Describe sodium transport within the thick ascending loop.

Answer 35

* **ATPase pumps actively remove sodium** from the tubular cells into the juxtamedullary fluid * Have a high mitochondria density to supply ATP

Question 36

Describe the interstitial osmolarity gradient progressing downwards of the nephron.

Answer 36

* **Increasingly hyperosmolar**

Question 37

Why is the ascending limb impermeable to water?

Answer 37

* Presence of **tight junctions** reduces paracellular transport of water

Question 38

Which transporter pumps sodium ions out of the thick ascending limb?

Answer 38

* Na⁺/K⁺ ATPase pump

Question 39

What are the 2 effects of the Na⁺/K_⁺ ATPase pump?

Answer 39

* **Removal of sodium** while retaining water leads to **hypotonic filtrate to the distal convoluted tubule** * **Pumping of sodium into the interstitial space** generates a **hyperosmotic interstitial fluid environment in the kidney medulla**

Question 40

What are the roles of principal cells?

Answer 40

* **Sodium reabsorption & potassium secretion** * Principal cells have a low mitochondrial density due to the passive diffusion of sodium ions intracellularly, and potassium efflux * **Aldosterone** regulates **Na⁺ reabsorption** by **increasing apical Na⁺ channels & basolateral Na⁺/K⁺ ATPase pumps** * **Anti-diuretic hormone (ADH)** regulates water reabsorption by **increasing apical aquaporins** (Present within intracellular vesicles, ADH signals increased vesicle fusion to embed aquaporins)

Question 41

What are the main causes of central diabetes insipidus?

Answer 41

* **Decreased / negligent production and release of ADH** (stroke, organic brain disease)

Question 42

What are the clinical features of CDI (3)? How is it confirmed?

Answer 42

* **Polyuria** * **P****olydipsia** * **Nocturia** * Water deprivation test to confirm & measure HbA1C

Question 43

What is the treatment of CDI?

Answer 43

* External ADH

Question 44

What is the syndrome of inappropriate antidiuretic hormone secretion (SIADH)?

Answer 44

* Increased production and release of ADH

Question 45

What are the clinical features of SIADH (3)?

Answer 45

* **Hyperosmolar urine** * **Hypervolaemia** * **Hyponatremia**

Question 46

What is the treatment for SIADH?

Answer 46

* **Fluid & water restriction** * If ineffective / chronic **non-peptide inhibitor of ADH receptor** (Conivaptan and tolvaptan)

Question 47

What is the cause of Nephrogenic Diabetes Insipidus (NDI)?

Answer 47

* Less/mutant AQP2 OR * Mutant V2 receptor

Question 48

What are the clinical features of Nephrogenic Diabetes Insipidus (NDI) (2)?

Answer 48

* Polyuria * Polydipsia

Question 49

What is the treatment of NDI?

Answer 49

* Thiazide diuretics + NSAIDs

Question 50

True or False: Osmolarity for 100mmol/L NaCl is less than 200mmol/L Na+ ions.

Answer 50

False

Question 51

True or False: Intravenous fluid infusion first enters intracellular fluid (ICF) and then travels to extracellular fluid (ECF) compartment.

Answer 51

False

Question 52

True or False: NaCl and urea are responsible for creating a hyperosmotic medullary interstitium.

Answer 52

True

Question 53

True or False: One of the body’s response to increased plasma osmolarity is the trigger of thirst.

Answer 53

True

Question 54

True or False: ADH regulates the number of aquaporin channels on both apical and basolateral membranes of the principal cells.

Answer 54

True

Question 55

True or False: The blood of patients with SIADH will slowly get more hyperosmotic.

Answer 55

False