Week 1: Na+ and H2O transporters along nephron, proximal tubule

Question 1

ID the main Na transporters in PT, TALH (thick ascending loop of hence), DCT, CCD (cortical CD), OMCD /IMCD (outer/inner medullary collecting duct), and their location in apical vs. basolateral side.

Answer 1

All have Na/K ATPase on basolateral side. Rest of these transports are on apical side.

• PT: NHE, Na/cotransport
• TALH: NKCC, NHE
• DCT:Na-Cl cotransport
• CD: CCD-Na channels, IMCD-amiloride sensitive Na channels

Question 2

ID the main water transporters in PT, Loop of Henle, early DT, late DT to Collecting duct, and their location in apical vs. basolateral side.

Answer 2

• PT: AQP1 (apical and basolat), 60-67% reabsorbed
• Loop: AQP1 in descending limb only, none in TALH, 10-15% reabsorbed
• early DT: none
• late DT to collecting duct: apical AQP2, basolat AQP3,4, 5-24% reabsorbed, AQP2 regulated by ADH and ANP

Question 3

What is the main function of the proximal tubule?

Answer 3

-reabsorption of the bulk of the filtered load in order to deliver a relatively constant amount of material to the loop of Henle and distal tubule/collecting ducts for fine adjustment

Question 4

Describe transport in the first half of the proximal tubule.

Answer 4

• Na: Na is pumped out on basolateral side by Na/K ATPase (driving force). Na enters on apical side via NHE and Na/glucose or AA cotransport, and exits cell on basolateral side via Na/HCO3 transporters.
• HCO3-: H+ pumped out with NHE combines with HCO3- to make H2CO3, converted by CA (carbonic anhydrase) to H2O and CO2, which enter s the cell and is converted back to HCO3-. HCO3- exits basolateral side with Na/HCO3-transporter.

Question 5

Describe transport in the second half of proximal tubule.

Answer 5

• Na: pumped out basolateral side by Na/ATPase, enter apical side via NHE
• Cl: enters via Cl/anion exchanger apically, exits basolaterally via K/Cl cotransport
• the anion the moves out on apical side combines with H+ that moves out via NHE to form HAnion which moves through apical membrane directly into the cell, dissociates again and is recycled
• since no Cl-transport prior to this, the driving force for passive Cl transport is high tubular lumen Cl- concentration
• also has paracellular NaCl reabsorption

Question 6

How does each of the following affect PT salt and water reabsorption: renal nerve activity, angiotensin II, dopamine, high salt diet?

Answer 6

• renal nerve activity: increases PT reabsorption of NaCl, NaHCO3, H2O
• ATII: increases reabsorption
• dopamine and high salt: decreases reabsorption (dopamine is produced in PT during high salt intake)
• filtration fraction (GFR/RBF): increases driving force for reabsorption, plasma oncotic pressure in peritubular capillaries increases, providing driving force for increased fluid reabsorption in PT

Question 7

Compare fraction of the filtered load transported by the proximal tubule under normal conditions for water, sodium, chloride, bicarbonate, glucose, amino acids.

Answer 7

The PT is leaky epithelium, about 2/3 of filtered volume (GFR=120ml/min) is reabsorbed in the PT (80ml/min).  The fraction of the filtered load reabsorbed is as follows:
Na: 2/3
K: 2/3
Cl: .58
bicarbonate: .89
glucose: ~1
amino acids: ~1
HCO3- is preferentially reabsorbed over Cl- or NaCl. Cl- reabsorption in early PT is less than Na reabsorption, which sets up chemical gradient for Cl reabsorption in late PT

Question 8

Define osmotic diuresis. How can high plasma glucose cause it?

Answer 8

It is increased urination due to certain substances in the fluid filtered by the kidneys

• develops when solute concentration in tubular fluid exceeds reabsorptive capacity
• in high plasma glucose, it exceeds reabsorptive capacity. Glucose remains in PT and osmotic pressure due to glucose reduces fluid reabsorption, leading to increased urine flow and decreased ECF volume
• ->thirst and polydipsia