Na and H20 transporters in proximal tubule

Question 1

Overview of Na and H20 transporters 1

Answer 1

• Proximal tubule: NHE (Na/H+ exchanger) is antiporter bringing Na in and H+ out using Na gradient
• Na/Cotransporter (AAs, sugars going same direction as Na) using Na gradient
• Aquaporin1 (AQP1): for water to follow Na (into epithelia)
• Thick ascending limb (TAL): mostly NKCC2 which is a cotransporter of Na, K, and 2Cl all entering the cell
• Some NHE, no AQP (diluting segment)

Question 2

Overview of Na and H20 transporters 2

Answer 2

• Distal convoluted tubule: mostly NCC which couples Na w/ Cl, both entering the cell
• Also no AQP
• Collecting duct intercalated cell: ENaC, a Na channel, ROMK, a K channel that removes K from the cell (secretion), and AQP
• Important to note: all parts of tubule have Na/K ATPase at basolateral membrane to set up concentration gradients (moves Na out and K into cell)

Question 3

Na and H20 reabsorption along nephron 1

Answer 3

• Bulk of the Na and H20 reabsorption happens in proximal tubule (60-70%)
• This is b/c there are many Na channels (NHE, Naco) and AQPs in proximal tubule
• In Loop of Henle (LoH) there is 25-30% of Na reabsorption and 10-15% of H20 reabsorption
• B/c in LoH there is NKCC and NHE for Na, along w/ AQP in descending limb (no AQP in TAL!!)

Question 4

Na and H20 reabsorption along nephron 2

Answer 4

• There is a little Na reabsorption in distal tubule (NCC) and collecting duct (ENaC)
• There is no H20 reabsorption in early distal tubule (no AQP), but there is 5-25% of H20 reabsorbed in late distal and collecting duct (AQP present)

Question 5

Overview of reabsorption process

Answer 5

• Reabsorption of bulk of filtered load (Na/H20) happens in proximal tubule
• Allows for relatively constant amount of material to be delivered to LoH
• Then there is fine adjustment of Na/H20 in distal tubule and collecting duct

Question 6

Notes on reabsorption 1

Answer 6

• Reabsorption is isoosmotic (osmolarity isn’t changing b/c H20 is reabsorbed w/ solutes)
• Na/K ATPase sets up the Na gradient (favoring reabsorption) and drives solute and fluid reabsorption
• K reabsorption happens by solvent drag (is reabsorbed by following H20, which is following Na)

Question 7

Notes on reabsorption 2

Answer 7

• No net secretion of K in PT b/c K is recycled (basolateral K channels) after ATPase to be used for ATPase again
• Na can be thought of as being reabsorbed as either NaHCO3 or NaCl
• HCO3- is preferentially reabsorbed over Cl- in early proximal tubule
• Cl- is preferentially reabsorbed over HCO3- in late PT

Question 8

HCO3 reabsorption 1

Answer 8

• HCO3- is filtered thru glomerulus and in early PT it combines w/ a H+ that was moved into lumen via NHE
• When H2CO3 formed there it is broken into H20 and CO2 via carbonic anhydrase on the apical membrane surface
• Both H20 and CO2 can cross the membrane (H20 using AQP) into the cell

Question 9

HCO3 reabsorption 2

Answer 9

• In the cell carbonic anhydrase will combine the H20 and CO2 to form H2CO3 which dissociates into HCO3- and H+ (pH dependent)
• The HCO3- uses a cotransporter w/ Na on the basolateral side to exit the cell and enter the blood for reabsorption
• The H+ is used by NHE to be removed back into the lumen and the cycle starts over

Question 10

Cl reabsorption 1

Answer 10

• In the late proximal tubule, there is an apical antiporter that couples removal of an anion (HCO3-, OH-, etc) with intake of Cl-
• Once the anion is removed it combines w/ a H+ that was removed via NHE to form HAnion
• This is a neutral compound and can freely diffuse thru the membrane back into the cell where is dissociates into anion and H+ (pH dependent)

Question 11

Cl reabsorption 2

Answer 11

• The Cl- is pumped out of the basolateral membrane using a K/Cl cotransporter (based on K gradient)
• The H+ is used again for NHE and anion is used again to bring in more Cl
• There is also Na and Cl transport across tight junctions (directly into interstitium) in this region, the driving force of which is high [Cl]
• Movement of Cl causes a voltage difference that drives Na movement across the tight junction

Question 12

H20 reabsorption in PT

Answer 12

• Occurs by osmosis driven by high oncotic pressure in peritubular capillaries (due to concentrate plasma that is left in the blood after glomerulus)
• Since the glomerulus doesn’t filter albumin normally it will concentrate the plasma and increase the oncotic pressure
• This allows H20 to flow thru AQPs in basolateral and apical membranes back to the capillaries

Question 13

Regulation of Na and H20 transport

Answer 13

• Na (along w/ HCO2 and Cl) and H20 reabsorption are increased by renal nerve activity and angiotensin II
• ATII stimulates more NHE, and renal nerves stimulate more NHE and Na/K ATPase
• Increasing GFR also increases H20 reabsorption by increasing the oncotic pressure in the capillaries
• Na/H20 reabsorption are decreased by DA, (produced in PT during high salt intake and high BP) by reducing NHE and Na/K ATPase

Question 14

Osmotic diuresis

Answer 14

• Phenomenon when solute concentration in tubular fluid exceeds the reabsorptive capacity (Tmax)
• This leads to an elevated tubular oncotic pressure, leading to a decreased GFR and small percentage of glomerular filtrate reabsorbed
• Most common culprit is glc (diabetes)
• Glc remains in PT and increases its oncotic pressure leading to less fluid reabsorption
• This increases urine flow, but decreases ECF volume leading to thrust and polydipsia