Distal Tubule & Collecting Ducts

Question 1

2 segments of the Distal tubule

Answer 1

1. Early distal tubule (distal convoluted)

2. Late distal tubule (connecting tubule)

Question 2

3 segments of the collecting duct

Answer 2

1. Cortical
2. Outer medullary
3. Inner medullary

Question 3

How much NaCl and water reabsorption in distal and collecting

Answer 3

7-8%

Thus…referred to as the ‘fine tuners’ of the nephron

Short term physiological regulation of urine flow and sodium excretion is mediated primarily by adjustments in the DT and CD NaCl and water reabsorption

Question 4

Cell types of the distal tubule

Answer 4

Early distal tubule = distal convoluted cell

Late distal tubule = connecting tubule cell (75%) + intercalated cell (25%)

Question 5

Collecting duct cell types

Answer 5

Cortical: principal/intercalated (75/25)

Outer: principal/intercalated (80/20)

Inner: 99/1

Question 6

Which cells in the distal tubules and collecting ducts have the primary function NaCl reabsorption?

Answer 6

Distal convoluted cell (early distal tubule)

Connecting tubule (late distal tubule)

Principal cells (collecting duct)

Question 7

Which cells in distal tubule and collecting duct have the function of H+ secretion into tubular fluid?

Answer 7

Intercalated cell (late distal —> collecting duct)

**barely any in the inner medullary collecting duct

Most of them in late distal and cortical duct

Question 8

Mechanism of NaCl reabsorption in the by early distal tubule (convoluted cells)

Answer 8

1. Basolateral Na/K ATPase pump
2. Intracellular Na drops
3. Gradient for Na/Cl cotransporter on apical membrane
4. Cl passively leaves basolateral membrane into interstitium

Question 9

Thiazide diuretics

Answer 9

Block Na/Cl cotransporter in the apical membrane on distal convoluted cells

‘Hydrochlorothiazide’

Inhibit NaCl reabsorption —> increase in urinary sodium excretion

**note: early distal tubule is IMPERMEABLE to water (so also considered a diluting segment like the ascending loop of Henle)

Question 10

Mechanism of NaCl reabsorption by late distal cells (connecting cells) and the principal cells (collecting cells)

Answer 10

1. basolateral Na/K pump
2. Na passively cross apical through Na channels
3. High K+ in cell —> K passively exit cell through K channels in both membranes (driven by net lumen negative potential gradient also)…major mechanism for regulating K+ excretion into urine
4. That negative lumen gradient also drives Cl- paracellular reabsorption (thus net NaCl reabsorption)

Question 11

Amiloride

Answer 11

Diuretic

Targets apical membran Na+ channels in late distal cells and principal cells in collecting duct

Question 12

What parts of the distal nephron can reabsorb water?

Answer 12

Late distal tubule (connecting tubule)

Collecting duct

NOT early distal tubule

Question 13

Hormone ADH

Answer 13

Increases the permeability of the apical membranes of the late distal tubule cells and the principal cells of the collecting duct to WATER

Water passively diffuses down its gradient into cells —> interstitium

Question 14

What segment plays a major role to concentrate urea in the tubular fluid

Answer 14

Collecting duct….

Cortical and outer medullary ducts are permeable to water (with ADH)….but not urea

Inner medullary duct —> permeable to urea and water (with ADH)…urea passively reabsorbed…net effect is still concentrated urea in urine….and also osmolality in interstitium of inner medulla is increased

This provides driving force for passive NaCl reabsorption by the thin ascending limb and for passive water reabsorption by inner medullary collecting tubule

Question 15

3 mechanisms that regulate NaCl and water reabsorption in distal tubule and collecting duct

Answer 15

1. Increase in [K+ plasma] —> increases Na/K pump rate —> increase Na/water reabsorption + K secretion
2. Increases in tubular fluid flow —> increase NaCl/water reabsorption + K secretion
3. Aldosterone stimulates net NaCl and water reabsorption and K secretion

Question 16

Effect of furosemide (diuretic) on distal tubule and collecting duct

Answer 16

Inhibits NaCl and K reabsorption in the thick ascending lopp

Therefore…

Increase NaCl and water delivery to late distal and collecting ducts….

Net increase in K secretion in distal tubule and collecting tubule…and eventually decrease K+ plasma levels (hypokalemia)

Question 17

Aldosterone mechanism on late distal and collecting duct cells

Answer 17

Stimulates synthesis and insertion of Na+ channels into apical membranes

Also synthesis and insertion of more Na/K pumps into basolateral membranes

Also stimulates synthesis of Krebs Cycle enzymes

Question 18

Chronic increases in aldosterone levels —>

Answer 18

Decrease in urinary NaCl and water excretion

Increase in urinary K+ levels (hypokalemia)

Question 19

Where are ADH (vasopressin) and oxytocin produced

Answer 19

Cell bodies of the magnocellular neurons located in the paraventricular nucleus and supraoptic nucleus of the hypothalamus

Transported down the axons…pass through the hypothalamic-hypophysial tract and terminate in the

Posterior pituitary gland…stored secretory vesicles until secreted into general circulation

Question 20

Mechanism how ADH stimulates water reabsorption from late distal tubule —> collecting duct

Answer 20

1. Binds to membrane ADH receptors
   - V1 = SmM cells of peripheral and renal arterioles —> vasoconstriction
   - V2 = basolateral membrane of late distal cells and principal cells
2. Activate adenylate cyclase
3. Increase production of CAMP in tubular cells
4. Activate PKA.
5. Insertion of vesicles containing aquaporin-2 channels into apical membrane

Question 21

Urea transport into inner medullary collecting duct cell

Answer 21

Passively across apical membrane urea transporter (UT1)

Exits basolateral via UT4

Question 22

Factors that influence ADH release from posterior pituitary

Answer 22

1. Plasma osmolality (primary regulator)
   - osmoreceptors in hypothalamus
   - increase in osmolality —> ADH released —> increase water reabsorption to dilute plasma to normal
2. Blood volume
   - volume receptors in cardiac atria
   - increase volume/stretch —> decrease ADH
   - decrease in volume —> increase ADH