Renal regulation of water and acid-base balance Flashcards
What is osmolarity?
Osmolarity: The concentration of osmotically active particles in solution, which maybe quantitatively expressed is osmoles of solute per litre of solution.
What does osmolarity depend upon?
• Osmolarity depends 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?
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 four forms of unregulated water loss?
Sweat
Faeces
Vomit
Water evaporation from respiratory lining and skin
What happens in a positive water balance?
High water intake,
ECF volume increases
This reduces the concentration of sodium and thus osmolarity
Hypo-osmotic urine production
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 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 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
Which hormone influences the permeability of the collecting duct to urea?
Vasopressin
What impact does urea have on the osmolarity of the interstitial fluid?
Increases the osmolarity by a significant magnitude
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
Which transporters allow urea into the thin descending limb of the loop of Henle?
UT-A2
Which neurones synthesise vasopressin?
Hypothalamic magnocellular neurones originating from the supraoptic and paraventricular nuclei
How many amino-acids long is vasopressin?
9 amino acids
What is the overall function of vasopressin?
Promotes water reabsorption from the DCT and collecting duct
What is the normal plasma osmolarity in a healthy adult?
275-290mOSm/kg
What % range change in osmolarity is required for the detection of baroreceptors?
5-10%
What factors stimulate ADH production?
Increase in plasma osmolarity Decrease in blood pressure Nausea Angiotensin II Nicotine Hypovolaemia
What factor inhibit ADH production?
Decreased plasma osmolarity
Hypervolaemia, increased blood pressure
Ethanol
ANP
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 happens upon AVP binding to G-protein linked V2 receptors within principal tubule cells?
Activates adenylate cyclase activity, generating cAMP - protein kinase promotes the migration of AQP 2 molecules towards the basolateral membrane
Which transporter pumps sodium ions out of the thick ascending limb?
Na+/K+ ATPase pump
What are the two 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 is diuresis?
Increased dilute urine excretion
There is minimal ADH influence
Overall reduced water reabsorption and hyposmolar urine
What is anti-diuresis?
Antidiuresis (Concentrated urine in low volume excretion)
In response to low plasma osmolarity or low blood pressure.
-Vasopressin supports sodium reabsorption in the thick ascending limb, distal
convoluted tubule and collecting duct – increasing hyperosmolar juxtamedullary
fluid concentration.
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?
Polyuria and polydipsia
Water deprivation test to
confirm & measure
HbA1C.
What is the treatment of CDI?
External ADH
What is SIADH?
Increased production and
release of ADH
What are the clinical features of SIADH?
Hyperosmolar urine
Hypervolaemia
Hyponatremia
What is the treatment for SIADH?
Non-peptide inhibitor of
ADH receptor (Conivaptan
and tolvaptan).
What is the treatment of NDI?
Mutant V2 receptor
unresponsive to
ADH stimulation
What are the clinical features of NDI?
Polyuria
Polydipsia
What is the treatment of NDI?
Thiazide diuretics +
NSAIDs.
What does carbonic acid dissociate into?
Bicarbonate and hydrogen ions
How is bicarbonate transported into the interstitium through the basolateral surface?
NBC-1 transporter
Which transporters secrete hydrogen ions into the tubular fluid?
NHE2 transporters
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 increases 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 two types of intercalated cells?
Alpha
Beta
What is the function of the alpha intercalated cells?
HCO3- reabsorption & H+ secretion.
What is the function of beta intercalated cells?
HCO3- secretion & H+ reabsorption.
What is an intercalated cell?
Intercalated cell: Secretes or absorbs acid/bicarbonate Regulation of blood
pH. Intercalated cells reabsorb K+ & HCO3-, while secreting H+. This function
reduces the acidity of the plasma, and subsequently increases urine acidity; this
mechanism is achieved by carbonic anhydrase activity.
Mitochondrial rich
Which amino acid within intercalated cells is used as a mediator for ammonia release?
Glutamine
How is ammonia transported into the filtrate?
NHE3 anti-porter
What happens to ammonia when in the filtrate?
Ammonia is protonated by hydrogen ions in the filtrate to form ammonium ions
The bicarbonate that dissociated from glutamine enters circulation
Which ion behaves as a urinary buffer in the tubular fluid?
Phosphate ions
