Distal Tubule & Collecting Ducts Flashcards
2 segments of the Distal tubule
- Early distal tubule (distal convoluted)
2. Late distal tubule (connecting tubule)
3 segments of the collecting duct
- Cortical
- Outer medullary
- Inner medullary
How much NaCl and water reabsorption in distal and collecting
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
Cell types of the distal tubule
Early distal tubule = distal convoluted cell
Late distal tubule = connecting tubule cell (75%) + intercalated cell (25%)
Collecting duct cell types
Cortical: principal/intercalated (75/25)
Outer: principal/intercalated (80/20)
Inner: 99/1
Which cells in the distal tubules and collecting ducts have the primary function NaCl reabsorption?
Distal convoluted cell (early distal tubule)
Connecting tubule (late distal tubule)
Principal cells (collecting duct)
Which cells in distal tubule and collecting duct have the function of H+ secretion into tubular fluid?
Intercalated cell (late distal —> collecting duct)
**barely any in the inner medullary collecting duct
Most of them in late distal and cortical duct
Mechanism of NaCl reabsorption in the by early distal tubule (convoluted cells)
- Basolateral Na/K ATPase pump
- Intracellular Na drops
- Gradient for Na/Cl cotransporter on apical membrane
- Cl passively leaves basolateral membrane into interstitium
Thiazide diuretics
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)
Mechanism of NaCl reabsorption by late distal cells (connecting cells) and the principal cells (collecting cells)
- basolateral Na/K pump
- Na passively cross apical through Na channels
- 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
- That negative lumen gradient also drives Cl- paracellular reabsorption (thus net NaCl reabsorption)
Amiloride
Diuretic
Targets apical membran Na+ channels in late distal cells and principal cells in collecting duct
What parts of the distal nephron can reabsorb water?
Late distal tubule (connecting tubule)
Collecting duct
NOT early distal tubule
Hormone ADH
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
What segment plays a major role to concentrate urea in the tubular fluid
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
3 mechanisms that regulate NaCl and water reabsorption in distal tubule and collecting duct
- Increase in [K+ plasma] —> increases Na/K pump rate —> increase Na/water reabsorption + K secretion
- Increases in tubular fluid flow —> increase NaCl/water reabsorption + K secretion
- Aldosterone stimulates net NaCl and water reabsorption and K secretion
Effect of furosemide (diuretic) on distal tubule and collecting duct
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)
Aldosterone mechanism on late distal and collecting duct cells
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
Chronic increases in aldosterone levels —>
Decrease in urinary NaCl and water excretion
Increase in urinary K+ levels (hypokalemia)
Where are ADH (vasopressin) and oxytocin produced
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
Mechanism how ADH stimulates water reabsorption from late distal tubule —> collecting duct
- Binds to membrane ADH receptors
- V1 = SmM cells of peripheral and renal arterioles —> vasoconstriction
- V2 = basolateral membrane of late distal cells and principal cells - Activate adenylate cyclase
- Increase production of CAMP in tubular cells
- Activate PKA.
- Insertion of vesicles containing aquaporin-2 channels into apical membrane
Urea transport into inner medullary collecting duct cell
Passively across apical membrane urea transporter (UT1)
Exits basolateral via UT4
Factors that influence ADH release from posterior pituitary
- Plasma osmolality (primary regulator)
- osmoreceptors in hypothalamus
- increase in osmolality —> ADH released —> increase water reabsorption to dilute plasma to normal - Blood volume
- volume receptors in cardiac atria
- increase volume/stretch —> decrease ADH
- decrease in volume —> increase ADH
