Renal Regulation of water and acid-base balance

Question 1

Define osmosis and osmolarity

Answer 1

Osmosis is the movement of water through a semi-permeable membrane from an area of low solute concentration to an area of high solute concentration until equilibrium is reached. Oncotic pressure is driven by the number of molecules.
Osmolarity = Concentration x No. of dissociated particles = Osm/L OR mOsm/L

Question 2

Describe body fluid distribution

Answer 2

2/3 is intracellular fluid. 1/3 is extracellular fluid - 1/4 of ECF is intravascular such as plasma and 3/4 is extravascular. 95% of extravascular fluid is interstitial fluid while 5% is transcellular fluid. Interstitial fluid surrounds and bathes different cells/tissues. Transcellular fluid examples are CSF/peritoneal fluid etc.

Question 3

What are unregulated and regulated methods of water loss?

Answer 3

Unregulated: Sweat, Feces, Vomit, Water evaporation from respiratory lining and skin
Regulated: Renal regulation – urine production

Question 4

Describe renal regulation

Answer 4

When there is a positive water balance due to high intake, increase in ECF volume means sodium concentration is decreased which leads to dip in osmolarity. Thus, hypoosmotic urine is produced to remove excess water and equilibrate osmolarity.

Question 5

Describe water reabsorption in the different parts of the nephron

Answer 5

67% of water reabsorption occurs in the PCT. In the descending limb, water is passively reabsorbed through gradient. The medullary interstitium needs to be hyperosmotic for water reabsorption to occur from the Loop of Henle and collecting duct. In the thin ascending limb, passive salt absorption occurs but no water reabsorption and in thick portion, active absorption of salt occurs. Variable amounts of water reabsorbed based on ADH action and body needs which modulate it.

Question 6

Describe the countercurrent multiplication principle

Answer 6

Active salt reabsorption occurs in the thick ascending portion of the loop of henle. This creates a hyperosmolar region in the medullary interstitium, drawing water out of the descending limb. As water is drawn out, filtrate at the bottom of the loop is the most hyperosmolar and hence greatest amount of salt reabsorption occurs here. Creates a gradient of osmolarity down the loop.

Question 7

What is urea recycling?

Answer 7

Urea filtered in Bowman’s capsule, travels through loop of Henle and into collecting duct. Transported through UT-A1 receptor on luminal side of collecting duct epithelial cell through UT-A3 receptor on basolateral side of epithelial cell. Concentration of urea in interstitium can be as high as 600 mmol/L. Once in the medullary region, urea can either go into the vasa recta through UT-B1 transporter or can enter thin descending limb of loop of Henle through UT-A2.

Question 8

What is the goal of urea recyling?

Answer 8

Urea recycling helps to increase osmolarity of interstitium required for 2 reasons: To concentrate the urine produced and urea excretion requires less water (when filtrate reaches medullary collecting duct, able to equilibrate with interstitium as high conc in interstitium so will have high conc in collecting duct as well thereby requiring less water.)

Question 9

How does ADH influence urea recyling?

Answer 9

Vasopressin boosts UT-A1 & UT-A3 numbers.

Question 10

Describe ADH

Answer 10

9 amino acid long protein. Promote water reabsorption from collecting duct. Produced in hypothalamus (neurons in supraoptic & paraventricular nuclei). Stored in the posterior pituitary.

Question 11

What factors influence ADH production and release?

Answer 11

Stimulatory: An increase in plasma osmolarity, hypovolemia, drop in blood pressure, nausea, angiotensin 2, nicotine
Inhibitory: Decrease in plasma osmolarity, hypervolemia, increase in blood pressure, ethanol, ANP

Question 12

How are osmolarity and blood pressure detected?

Answer 12

Plasma osmolarity: 275-290 mOsm/kg H20 (Healthy adult). Fluctuation detected by osmoreceptors in hypothalamus.
5-10% change required for detection by baroreceptors;
information transmitted to hypothalamus.

Question 13

Explain the mechanism of action of ADH

Answer 13

ADH binds to V2 receptors on basolateral membrane of principal cell in collecting duct. Activates G-protein pathway activating adenylate cyclase forming cAMP. Protein kinase A causes aquaporin 2 channels to fuse with the apical membrane. Allows greater water reabsorption which then travels into bloodstream through aquaporin 3 and 4 found in basolateral membrane.

Question 14

What is diuresis and how does it occur?

Answer 14

Diuresis is the production of increased dilute urine excretion. Occurs when ADH is zero or low. In the thick ascending limb, sodium reabsorbed via active transport by sodium potassium pump in basolateral surface of epithelial cell. This creates a low concentration of sodium within the cell, allowing for movement of sodium down concentration gradient from filtrate into cell – using energy of sodium, chloride and potassium ions also move into cell through triple transporter. Potassium and chloride then transported into blood in basolateral membrane through symporter but chloride can also move into blood through ion channel. Similarly, potassium can return to filtrate via ion channel in apical membrane.
Hypoosmolar fluid therefore produced at top of loop of Henle.

Question 15

Describe NaCl reabsorption in DCT

Answer 15

Sodium and chloride symporter allows ions in through apical membrane driven by sodium concentration gradient, created by sodium potassium ATPase pump. Potassium and chloride removed into bloodstream through symporter in basolateral membrane - chloride also travels through ion channel.

Question 16

Describe Na+ reabsorption in the principal cell

Answer 16

Travels through ion channel through apical membrane into the principal cell. Sodium reabsorbed through sodium potassium ATPase pump.

Question 17

What happens if ADH is high?

Answer 17

Antidiuresis - Concentrated urine in low volume excretion.
ADH supports Na+ reabsorption in:
Thick ascending limb: increases Na+ - K+ - 2Cl- symporter
Distal convoluted tubule: increases Na+ - Cl- symporter
Collecting duct: increases Na+ channel

Question 18

Describe central diabetes insipidus

Answer 18

Cause: Decreased/negligent production and release of ADH
Clinical features: Polyuria, polydipsia
Treatment: External ADH

Question 19

Describe Syndrome of inappropriate ADH secretion (SIADH)

Answer 19

Cause: Increased production and release of ADH
Clinical features: Hyperosmolar urine, Hypervolemia, Hyponatremia
Treatment: Non-peptide inhibitor of ADH receptor (conivaptan & tolvaptan)

Question 20

Describe nephrogenic diabetes insipidus

Answer 20

Cause: Less/mutant aquaporin-2, mutant V2 receptor
Clinical features: Polyuria, polydipsia
Treatment: Thiazide diuretics + NSAIDs

Question 21

Why is acid base balance important?

Answer 21

Acid and base constantly added to body due to diet and metabolism. Bases mainly excreted in faeces and so there is a net addition of metabolic acid to our fluid compartments – important to utilize this as can impact blood pH otherwise. Normal blood pH is 7.4.

Question 22

How is acid base balance maintained?

Answer 22

Primarily acids neutralized by buffer systems (bicarbonate buffer system producing bicarbonate and carbon dioxide). Maintenance of bicarbonate levels by kidneys. 
3 roles of kidney:
Secretion & excretion of H+
Reabsorption of HCO3-
Production of new HCO3-

Question 23

Describe reabsorption of bicarbonate ions across nephrons

Answer 23

80% absorbed in PCT, 10% in thick ascending limb of loop of henle, 6% in DCT, 4% in collecting duct

Question 24

Describe how bicarbonate ions are reabsorbed in the PCT

Answer 24

1. CO2 enters cell by diffusion and by action of carbonic anhydrase, creates hydrogen ion and bicarbonate ion.
2. Proton ion can leave cell and enter tubular fluid – firstly, can go through NHE3 transporter where energy of sodium travelling down into cell used to transport the proton. Secondly, H+ ATPase pump can be used to transport H+ out.
3. Bicarbonate symporter NBC1 moves bicarbonate along with sodium into the bloodstream.
4. H+ transported out into tubular fluid combines with bicarbonate ions to form H2CO3 which is broken down into water and carbon dioxide, providing a supply of carbon dioxide.

Question 25

What are the roles of the different intercalated cells in the DCT and collecting ducts?

Answer 25

⍺-Intercalated cell: HCO3- reabsorption & H+ secretion.

β-Intercalated cell: HCO3- secretion & H+ reabsorption.

Question 26

Describe bicarbonate ion reabsorption in alpha intercalated cell

Answer 26

1. Carbon dioxide diffuses into cell and reacts with water catalysed by carbonic anhydrase to form bicarbonate ion and H+.
2. Bicarbonate ion absorbed from basolateral surface via chloride bicarbonate antiporter. Chloride removed from cell through ion channels basolaterally.
3. H+ removed into lumen through H+ ATPase and H+-K+ ATPase.

Question 27

Describe activity of beta intercalated cell

Answer 27

1. Bicarbonate and H+ formed.
2. Bicarbonate removed into lumen through bicarbonate-chloride antiporter.
3. H+ removed basolaterally through H+ ATPase while chloride exits via ion channels.

Question 28

Describe how bicarbonate ions are produced in the proximal convoluted tubule

Answer 28

One molecule of glutamine gives rise to 2 ammonia ions and a divalent ion which is then broken down into two bicarbonate ions, absorbed into the blood. The ammonia ions are then converted into one urea ion and one proton ion – sodium proton antiporter NHE3 used to remove ammonia ion from cell or converted to ammonia gas which diffuses into tubular fluid space and combines with a H+ ion to form an ammonia ion.