(5) Reabsorption and secretion in the distal tubule and collecting duct

3 segments of distal tubule

distal convoluted tubule(DCT), connecting tubule(CNT), and initial collecting duct (ICT).

(ultrastructure) Distal convoluted tubule

1st segment of distal tubule. DCT is very similar to cells of the TAL. (mitochondria associated with extensive basal membrane interdigitations. More complex and cuboidal and more involved in absorption and secretion)

(ultrastructure) Connecting tubule

2nd segment of distal tubule. CNT has 2 cell types (connecting-tubule/principal cells and intercalated cells). These 2 cell types are seen through the rest of the nephron segment.

(ultrastructure) Initial collecting duct

last segment of distal tubule. In the ICT, there are 1/3rd intercalated cells and ⅔ principal cells.Also, alpha- and beta-inter-calated cells. Principal cells (replace the similar connecting- tubule cells) have a central cilium and invaginated basolateral membranes.

Aldosterone stimulates sodium reabsorption in what types of cells?

principal and principal-like

3 segments of the collecting duct

cortical collecting duct (CCT), outer medullary collecting duct(OMCD), and inner medullary collecting duct(IMCD).

(ultrastructure) cortical collecting duct (CCT)

1st segment of collecting duct. 2:1 ratio of principal to intercalated cells.

(ultrastructure) outer medullary collecting duct(OMCD) and inner medullary collecting duct(IMCD)

2nd and last segment of collecting duct. Single cell type that becomes taller as you move deeper into the medulla and the epithelium becomes tighter

Main responsibility of the distal nephron and collecting duct system

tightly regulated control of salt and water reabsorption

How is NaCl reabsorbed in the distal convoluted tubule?

across apical membrane via thiazide-sensitive Na/Cl cotransporter (luminal). Cl- moves across basolateral membrane via a channel and the Na+ is pumped across

Thiazaide diuretic

prescribed for hypertension. Targets thiazide sensitive Na/Cl cotransporter in the DCT in order to decrease uptake of NaCl

Gitelman syndrome

defective thiazide-sensitive NaCl cotransporter in the distal convoluted tubule which causes decreased NaCl reabsorption in the kidney and hypotension

Where are principal or principal-like cells found?

connecting tubule (Distal Tubule), initial collecting duct (Distal Tubule) and cortical collecting duct (Collecting Duct)

How is NaCl reabsorbed in principal or principal-like cells?

amiloride-sensitive epithelial Na+ channel (ENaC) on the luminal membrane. Cl- reabsorption by paracellular diffusion is driven by the super negative Vte established by ENaC. also promotes potassium secretion

Liddle syndrome

increased ENaC activity in principle cells increases Na/Cl reabsorption leading to hypertension

How do beta-intercalated cells contribute to Na or Cl reabsorption?

Cl-HCO3 exchanger that is coupled to acid-base handling (only contributes to Cl- reabsorption)

Aldosterone

hormone secreted by the adrenal cortex that targets principle or principle-like cells. Increases activity and expression of epithelial sodium channels on the tubule lumen.

Stimulators of aldosterone

angiotensin II, sympathetic activation (volume contracted), hyperkalemia, and stress/trauma

Spironolactone

diuretic that blocks action of aldosterone by competing for the receptor. Decreases sodium reabsorption to combat hypertension

t/f water reabsorption in the nephron is active

false, it is passive and follows solute reabsorption

How is H2O reabsorption affected by the absence of anti-diuretic hormone?

H2O permeability of the TAL and further downstream is low, and solute reabsorption creates a hypoosmotic tubule fluid relative to the interstitium

How is H2O reabsorption affected by the presence of anti-diuretic hormone?

H2O permeability increases, and the osmotic gradient drives the passive reabsorption of H2O

How is potassium secreted by principal cells

ENaC draws potassium into the cell and across the apical membrane due to very negative lumen voltage that it generates

How is potassium reabsorbed in the distal tubule/collecting duct

occurs in alpha-intercalated cells. Luminal H-K pump and basolateral K+ channel. Reabsorption is coupled to secretion of of H+

Why can hypokalemia lead to alkalosis?

potassium reabsorption in alpha-intercalated cells is coupled to secretion of of H+

Show the difference in acid-base handling by alpha intercalated cells vs beta intercalated cells

alpha is involved in H+ secretion while beta is involved in HCO3- secretion. The expression of the Cl-HCO3 exchanger is flipped from basolateral on alpha to apical on beta

How is calcium reabsorbed in the distal convoluted tubule?

similar to the transcellular process in the PT and TAL. stimulated by parathyroid hormone and vitamin D.

How is DCT calcium reabsorption regulated?

tightly regulated via stimulation by parathyroid hormone (PTH) and vitamin D