L6 Renal diluting segments and collecting system

Question 1

Parts of the nephron that are persistently water permeable?

Aquaporin Expression?

Answer 1

Proximal Tubule and Descending Loop of Henle

AQP1 expressed on apical and basolateral membrane (Primary Channel)

AQP7 also expressed on apical membrane of straight PT

Question 2

Parts of the nephron whose water permeability is regulated by ADH?

Aquaporin Expression?

Answer 2

Late part of distal convoluted tubule and collecting tubule

➢ Constitutive (constant) AQP3 and AQP4 expression in the basolateral membrane of principal cells

➢ Facultative AQP2 expression in apical membrane of principal cells regulated by ADH

Question 3

Transsellar Reabsorption in the Thick Ascending Limb

Movement of Na+ across apical membrane mediated by ___________________.

Presence of K+ channels on apical membrane essential for continued operation

Movement of Na+ across the apical membrane is also mediated by ______________

Answer 3

Movement of Na+ across apical membrane mediated by NKCC2 symporter (1Na+/1K+/2Cl-)

Presence of K+ channels on apical membrane essential for continued operation of the NKCC2 symporter

Movement of Na+ across apical membrane is also mediated by Na+/H+ antiporter

Question 4

Reabsorption in the Thin Descending Limb?

Answer 4

Water is reabsorbed via AQP1

NaCl is not reabsorbed

Question 5

Reabsorption in the Thin/Thick Ascending Limb?

Answer 5

Water is not reabsorbed (NO AQUAPORIN CHANNELS)

NaCl (~25% of filtered load) is reabsorbed by transcellular and paracellular pathways (50:50 ratio)

Question 6

A dominance of ______________ in the apical membrane of TAL cells results in a lumen-positive voltage. This positive voltage drives the ____________ reabsorption of several cations (_______, ______, _______, and _______)

Answer 6

A dominance of K+ channels in the apical membrane of TAL cells results in a lumen-positive voltage. This positive voltage drives the paracellular reabsorption of several cations (Na+, K+, Mg2+, and Ca2+)

Question 7

Which part of the nephron is known as the diluting segment?

Answer 7

Thick Ascending Limb

Question 8

How do loop diuretics work?

Answer 8

NKCC2 cotransporter is inhibited by loop diuretics
=> Transcellular voltage difference falls
==>Paracellular reabsorption (Na+, K+, Ca2+, Mg2+) is reduced
===>WATER FOLLOWS SOLUTES, with more solutes remaining in the ultra filtrate, more water is secreted

Question 9

Loop diuretics are actively secreted into the tubules by __________

Answer 9

Loop diuretics are actively secreted into the tubules by the organic anion transporter (OAT) System

Question 10

__________ is inhibited by loop diuretics

Answer 10

NKCC2 cotransporter is inhibited by loop diuretics (Thick Ascending Limb)

Question 11

__________ is inhibited by thiazide diuretics

Answer 11

NCC symporter is inhibited by thiazide diuretics (EARLY Distal Convoluted Tubule)*

Question 12

Na reabsorption in early DCT?

Basolateral _______________ maintains a low intracellular [Na +] in the early distal convoluted tubule (DCT)

Entry of NaCl across the apical membrane is mediated by a _________________

Cl- leaves the cell via diffusion via __________

The early DCT is _________ to water thus dilution of tubular fluid continues

Answer 12

Na reabsorption in early DCT?

Basolateral Na K ATPase maintains a low intracellular [Na ++] in the early distal convoluted tubule (DCT)

Entry of NaCl across the apical membrane is mediated by a Na Cl symporter (NCC)

Cl- leaves the cell via diffusion through Cl- channels

The early DCT is impermeable to water thus dilution of tubular fluid continues

Question 13

Basolateral _______________ maintains a low intracellular [Na +] in the early distal convoluted tubule (DCT)

Entry of NaCl across the apical membrane is mediated by a _________________

Cl- leaves the cell via diffusion via __________

The early DCT is _________ to water thus dilution of tubular fluid continues

Answer 13

Basolateral Na K ATPase maintains a low intracellular [Na ++] in the early distal convoluted tubule (DCT)

Entry of NaCl across the apical membrane is mediated by a NCC (Na/Cl) symporter

Cl- leaves the cell via diffusion through Cl- channels

The early DCT is impermeable to water thus dilution of tubular fluid continues

Question 14

Cell types of the LATE DCT/Collecting Ducts and their functions?

Answer 14

Principal cells (80% of cells):

• Reabsorb Na+, Cl-and water and secrete K+
• Solute movement dependent on activity of the Na+/K+
• ATPase in basolateral membrane (Aldosterone Mediated)

Intercalated cells (20% of cells):

• Primarily involved in Acid/Base Ballance
• Reabsorb K+ and secrete either H+ or HCO3-
• Solute movement dependent on activity of the H+/K+-ATPase in apical membrane

Question 15

_____________ are inhibited by amiloride

Answer 15

ENaC channels are inhibited by amiloride (Distal DCT)

Question 16

Proximal Tubule: % Na+ Absorbed/Transporters

Answer 16

65-67%

Na+/H+ Antiporter
Na+ Symporter w/ Glucose, Amino Acids, Organic Solutes
Paracellular

Question 17

Loop Of Henly: % Na+ Absorbed/Transporters

Answer 17

25%

NKCC2 Symporter (1Na+/1K+/2Cl-)
Na+/H+ Antiporter
Paracellular

Question 18

Distal Convoluted Tubule: % Na+ Absorbed/Transporters

Answer 18

EARLY: NaCl (NCC) Symporter
LATE: Na+ (ENaC) Channels

Question 19

Collecting-Duct System: % Na+ Absorbed/Transporters

Answer 19

~3%

Na+ (ENaC) Channels

Question 20

Expression and Regulation of ENac in the Nephron?

Answer 20

The aldosterone-regulated epithelial Na+ channel (ENaC) is not present in the early DCT, but increases in abundance through the late DCT and is strongly expressed in the collecting duct.

Question 21

What determines the volume of water absorbed by the Collecting Duct?

Answer 21

The volume of water absorbed by the Collecting Duct depends on the presence or absence of anti-diuretic hormone (ADH)

In the absence of ADH, the inner medullary collecting duct has at least a finite water permeability but the outer medullary and cortical regions have extremely low water permeability without ADH

Question 22

In the absence of ADH, the _______________ has a finite water permeability but the _____________and ____________ have extremely low water permeability

Answer 22

In the absence of ADH, the inner medullary collecting duct has a finite water permeability but the outer medullary and cortical regions have extremely low water permeability

Question 23

Mechanism of ADH Action?

Answer 23

Presence of ADH
ADH binds to V2 receptor on basolateral membrane of collecting duct cells
==> V2 Receptor activates cAMP second messenger system
===> AQP2 water channels inserted on apical membrane
====>water reabsorbed by osmosis to the blood via constitutively expressed basolateral (AQP3 and AQP4)

Absence of ADH
With the removal of ADH, AQP2 channels are re-internalized into the cell and the apical membrane is once again impermeable to water