Regulation of Water Balance Flashcards
Part of "Renal Regulation of Water and Acid-Base Balance" lecture
What is osmolarity?
- 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
What does osmolarity depend upon?
- On the intrinsic property of the substance and dissociation capacity
- Ionic compounds have the ability to dissociate into respective ions
What are the 2 compartments of fluid in the human body?
- Intracellular fluid (2/3)
- Extracellular fluid (1/3)
How is extracellular fluid divided?
- 3/4 Extravascular
- 1/4 Intravascular
What is transcellular fluid?
- Refers to fluid that resides within epithelial lined spaces (cerebrospinal fluid and peritoneal fluid)
What are 4 forms of unregulated water loss?
- Sweat
- Faeces
- Vomit
- Water evaporation from respiratory lining and skin
What is the form of regulated water loss?
- Renal regulation - urine production
What happens in a positive water balance?
High water intake → Increase ECF volume / Decrease [Na+] → Decrease osmolarity → Hypoosmotic urine production
What happens in a negative water balance?
Low water intake → Decrease ECF volume / Increase [Na+] → Increase osmolarity → Hyperosmotic urine production
Which transporters allow urea into the thin descending limb of the loop of Henle?
UT-A2
Which urea transporters are located on the apical cell surface membrane of the collecting duct, allowing the passage of urea into the tubule cells?
UT-A1
What is the UT-A3 transporter?
- Present on the basolateral cell membrane of the collecting duct, facilitating the passage of urea from the tubule cells into the medullary interstitium
How is urea reabsorbed into the vasa recta?
- Via UT-B1 transporters
What effect does vasopressin have on urea transporter?
- Vasopressin up-regulates UT-A1 and UT-A3, potentiating the increase of urea transport into the medullary interstitial fluid
What impact does urea have on the osmolarity of the interstitial fluid?
- Increases the osmolarity by a significant magnitude
Which hormone influences the permeability of the collecting duct to urea?
- Vasopressin / Antidiuretic Hormone / ADH
How many amino-acids long is vasopressin?
- 9 amino acids
What is the main function of vasopressin?
- Promotes water reabsorption from the DCT and collecting duct
Which neurones synthesise vasopressin?
- Hypothalamic magnocellular neurones originating from the supraoptic and paraventricular nuclei
- Produced in the Hypothalamus
- Stores in the Posterior Pituitary
What factors stimulate ADH production (5)?
- Increase in plasma osmolarity
- Hypovolaemia, decreased blood pressure
- Nausea
- Angiotensin II
- Nicotine
What factor inhibit ADH production (4)?
- Decreased plasma osmolarity
- Hypervolaemia, increased blood pressure
- Ethanol
- Atrial natriuretic hormone (ANP)
What is the normal plasma osmolarity in a healthy adult?
- 275-290 mOSm/kg
Fluctuation detected by osmoreceptors in hypothalamus
What % range change in osmolarity is required for the detection of baroreceptors?
- 5-10%
What is the mechanism of action of ADH (5)?
- ADH binds to V2 receptor in basolateral membrane of the principal cell
- Binding to V2 activates G protein mediated signalling cascade
- Activates adenylate cyclase: ATP -> cAMP -> PKA -> increases secretion of AQP2
- AQP2 transported to apical membrane
- H2O flows through AQP3 or AQP4 into blood
What happens upon AVP binding to G-protein linked V2 receptors within principal tubule cells (2 steps)?
- Activates adenylate cyclase activity, generating cAMP. Protein kinase promotes the migration of AQP 2 molecules towards the basolateral membrane
Which receptors does AVP bind to on tubule cells?
- G-protein linked V2 receptors on the basolateral cell surface membrane of principal tubule cells of the collecting duct
What is diuresis?
- Diluted urine in high volume excretion
What is the amount of ADH in diuresis?
Low to Zero
How does the: Thick ascending limb / Distal convoluted tubule / Collecting duct change in diuresis?
- Thick ascending limb: Inhibit Na+ / K+ / 2Cl- symporter
- Distal convoluted tubule: Inhibit Na+ / Cl- symporter
- Collecting duct: Inhibit Na+ channel
What is antidiuresis?
- Concentrated urine in low volume excretion
What is the ADH amount in antidiuresis?
High
How does the: Thick ascending limb / Distal convoluted tubule / Collecting duct change in antidiuresis?
- Thick ascending limb: Stimulate Na+ / K+ / 2Cl- symporter
- Distal convoluted tubule: Stimulate Na+ / Cl- symporter
- Collecting duct: Stimulate Na+ channel
Which channels are integrated within the descending limb to facilitating water leaving the loop of henle and entering into the hyperosmolar interstititum?
- Aquaporin channels
Describe the permeability to water in the ascending limb.
- Impermeable to water due to the absence of aquaporin channels
Describe sodium transport within the thick ascending loop.
-
ATPase pumps actively remove sodium from the tubular cells into the juxtamedullary fluid
- Have a high mitochondria density to supply ATP
Describe the interstitial osmolarity gradient progressing downwards of the nephron.
- Increasingly hyperosmolar
Why is the ascending limb impermeable to water?
- Presence of tight junctions reduces paracellular transport of water
Which transporter pumps sodium ions out of the thick ascending limb?
- Na+/K+ ATPase pump
What are the 2 effects of the Na+/K+ ATPase pump?
- 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
What are the roles of principal cells?
-
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)
What are the main causes of central diabetes insipidus?
- Decreased / negligent production and release of ADH (stroke, organic brain disease)
What are the clinical features of CDI (3)? How is it confirmed?
- Polyuria
- Polydipsia
- Nocturia
- Water deprivation test to confirm & measure HbA1C
What is the treatment of CDI?
- External ADH
What is the syndrome of inappropriate antidiuretic hormone secretion (SIADH)?
- Increased production and release of ADH
What are the clinical features of SIADH (3)?
- Hyperosmolar urine
- Hypervolaemia
- Hyponatremia
What is the treatment for SIADH?
-
Fluid & water restriction
- If ineffective / chronic non-peptide inhibitor of ADH receptor (Conivaptan and tolvaptan)
What is the cause of Nephrogenic Diabetes Insipidus (NDI)?
- Less/mutant AQP2
OR - Mutant V2 receptor
What are the clinical features of Nephrogenic Diabetes Insipidus (NDI) (2)?
- Polyuria
- Polydipsia
What is the treatment of NDI?
- Thiazide diuretics + NSAIDs
True or False: Osmolarity for 100mmol/L NaCl is less than 200mmol/L Na+ ions.
False
True or False: Intravenous fluid infusion first enters intracellular fluid (ICF) and then travels to extracellular fluid (ECF) compartment.
False
True or False: NaCl and urea are responsible for creating a hyperosmotic medullary interstitium.
True
True or False: One of the body’s response to increased plasma osmolarity is the trigger of thirst.
True
True or False: ADH regulates the number of aquaporin channels on both apical and basolateral membranes of the principal cells.
True
True or False: The blood of patients with SIADH will slowly get more hyperosmotic.
False
