Renal regulation of water and acid-base balance

Question 1

What is osmolarity?

Answer 1

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

Question 2

What does osmolarity depend upon?

Answer 2

• Osmolarity depends 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?

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 four forms of unregulated water loss?

Answer 6

Sweat
Faeces
Vomit
Water evaporation from respiratory lining and skin

Question 7

What happens in a positive water balance?

Answer 7

High water intake,

ECF volume increases

This reduces the concentration of sodium and thus osmolarity

Hypo-osmotic urine production

Question 8

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

Answer 8

Aquaporin channels

Question 9

Describe the permeability to water in the ascending limb

Answer 9

Impermeable to water to the absence of aquaporin channels

Question 10

Describe sodium transport within the thick ascending loop

Answer 10

ATPase pumps actively remove sodium from the tubular cells into the juxtamedullary fluid

Have a high mitochondria density to supply ATP

Question 11

Describe the interstitial osmolarity gradient progressing downwards of the nephron

Answer 11

Increasingly hyperosmolar

Question 12

Why is the ascending limb impermeable to water?

Answer 12

Presence of tight junctions reduces paracellular transport of water

Question 13

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 13

UT-A1

Question 14

What is the UT-A3 transporter?

Answer 14

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

Question 15

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

Answer 15

Vasopressin

Question 16

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

Answer 16

Increases the osmolarity by a significant magnitude

Question 17

How is urea reabsorbed into the vasa recta?

Answer 17

Via UT-B1 transporters

Question 18

What effect does vasopressin have on urea transporter?

Answer 18

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

Question 19

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

Answer 19

UT-A2

Question 20

Which neurones synthesise vasopressin?

Answer 20

Hypothalamic magnocellular neurones originating from the supraoptic and paraventricular nuclei

Question 21

How many amino-acids long is vasopressin?

Answer 21

9 amino acids

Question 22

What is the overall function of vasopressin?

Answer 22

Promotes water reabsorption from the DCT and collecting duct

Question 23

What is the normal plasma osmolarity in a healthy adult?

Answer 23

275-290mOSm/kg

Question 24

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

Answer 24

5-10%

Question 25

What factors stimulate ADH production?

Answer 25

``` Increase in plasma osmolarity Decrease in blood pressure Nausea Angiotensin II Nicotine Hypovolaemia ```

Question 26

What factor inhibit ADH production?

Answer 26

Decreased plasma osmolarity Hypervolaemia, increased blood pressure Ethanol ANP

Question 27

Which receptors does AVP bind to on tubule cells?

Answer 27

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

Question 28

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

Answer 28

Activates adenylate cyclase activity, generating cAMP - protein kinase promotes the migration of AQP 2 molecules towards the basolateral membrane

Question 29

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

Answer 29

Na+/K+ ATPase pump

Question 30

What are the two effects of the Na-K-ATPase pump?

Answer 30

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 31

What is diuresis?

Answer 31

Increased dilute urine excretion There is minimal ADH influence Overall reduced water reabsorption and hyposmolar urine

Question 32

What is anti-diuresis?

Answer 32

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.

Question 33

What are the main causes of central diabetes insipidus?

Answer 33

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

Question 34

What are the clinical features of CDI?

Answer 34

Polyuria and polydipsia Water deprivation test to confirm & measure HbA1C.

Question 35

What is the treatment of CDI?

Answer 35

External ADH

Question 36

What is SIADH?

Answer 36

Increased production and | release of ADH

Question 37

What are the clinical features of SIADH?

Answer 37

Hyperosmolar urine Hypervolaemia Hyponatremia

Question 38

What is the treatment for SIADH?

Answer 38

Non-peptide inhibitor of ADH receptor (Conivaptan and tolvaptan).

Question 39

What is the treatment of NDI?

Answer 39

Mutant V2 receptor unresponsive to ADH stimulation

Question 40

What are the clinical features of NDI?

Answer 40

Polyuria | Polydipsia

Question 41

What is the treatment of NDI?

Answer 41

Thiazide diuretics + | NSAIDs.

Question 42

What does carbonic acid dissociate into?

Answer 42

Bicarbonate and hydrogen ions

Question 43

How is bicarbonate transported into the interstitium through the basolateral surface?

Answer 43

NBC-1 transporter

Question 44

Which transporters secrete hydrogen ions into the tubular fluid?

Answer 44

NHE2 transporters

Question 45

What are the roles of principal cells?

Answer 45

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).

Question 46

What are the two types of intercalated cells?

Answer 46

Alpha | Beta

Question 47

What is the function of the alpha intercalated cells?

Answer 47

HCO3- reabsorption & H+ secretion.

Question 48

What is the function of beta intercalated cells?

Answer 48

HCO3- secretion & H+ reabsorption.

Question 49

What is an intercalated cell?

Answer 49

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

Question 50

Which amino acid within intercalated cells is used as a mediator for ammonia release?

Answer 50

Glutamine

Question 51

How is ammonia transported into the filtrate?

Answer 51

NHE3 anti-porter

Question 52

What happens to ammonia when in the filtrate?

Answer 52

Ammonia is protonated by hydrogen ions in the filtrate to form ammonium ions The bicarbonate that dissociated from glutamine enters circulation

Question 53

Which ion behaves as a urinary buffer in the tubular fluid?

Answer 53

Phosphate ions