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Distal convoluted tubule (DCT)

Shortest nephron segment connecting the thick ascending limb to the collecting duct, located in cortex close to renal corpuscle

Macula densa

Specialized tall epithelial cells at the junction of the thick ascending limb and DCT that detect tubular NaCl concentration, releases adenosine (constricts afferent arteriole) in response to high flow rates

Juxtaglomerular (JG) cells

Modified smooth muscle cells in the tunica media of the afferent arteriole that contain and release renin (starts RAAS → angiotensin formation → sodium retention/arteriole constriction) during sustained increases in RBF

Distal convoluted tubule function

Reabsorbs NaCl (5%) and Ca2+, mostly water impermeable, contributes to dilution of urine, connects thick ascending limb to collecting duct

Early DCT

Water-impermeable segment containing Na+/Cl- cotransporters and TRPV5 calcium channels on the apical side, and pumpkins/ K+ and Cl- channels on the basolateral side

Late DCT

Contains aldosterone-responsive cells similar to principal cells

Na+/Cl- cotransporter (NCC)

Apical transporter that reabsorbs sodium and chloride in the DCT, inhibited by thiazide diuretics

DCT apical channels

NCC (Cl and Na IN from urine), TRPV5 (calcium IN from urine)

DCT basolateral channels

Pumpkins, chloride channel (Cl OUT to blood), potassium channel (recycles potassium OUT to blood)

Thiazide diuretics

Drug class that competitively inhibits the Na+/Cl- cotransporter in the DCT, used for hypertension/congestive heart failure, can lead to hyperlipidemia, decreased serum ions, dry eye, increased risk of hypokalemia with steroids

Collecting duct system

Receives urine from multiple nephrons (through multiple connecting tubules) and fine-tunes sodium (reabsorbs 5%, responds to external signals and hormones)

Principal cells

Collecting duct cells responsible for sodium and water reabsorption and potassium secretion, cilium, microvilli and small mitochondria, 60% of cells in CCD

Principal cells apical channels

ROMK (K+ OUT into urine), ENaC (Na+ IN to cell, creates large lumen negative potential difference),

Principal cells basolateral channels

Pumpkins, K+ channels (recycle K+ OUT into blood)

Intercalated cells

Collecting duct cells responsible for acid-base regulation and potassium handling, alpha and beta, microvilli and many mitochondria, 40% of cells in CCD

Alpha-intercalated cells

Secrete hydrogen ions via apical H+(/K+)-ATPase and reabsorb bicarbonate and potassium

Beta-intercalated cells

Secrete bicarbonate via apical HCO3/Cl- exchanger and reabsorb chloride

Lumen potential principal cells

Electrical gradient created by ENaC-mediated sodium reabsorption that drives potassium secretion and paracellular chloride reabsorption

Paracellular chloride reabsorption

Movement of chloride between cells driven by the lumen-negative electrical potential

Acid-base regulation in the collecting duct

Performed primarily by alpha- and beta-intercalated cells

Anion exchanger 1 (AE1)

Basolateral Cl-/HCO3- exchanger in alpha-intercalated cells

Pendrin

Apical Cl-/HCO3- exchanger in beta-intercalated cells that secretes bicarbonate and reabsorbs chloride

Potassium-sparing diuretics

Diuretics that inhibit ENaC in principal cells, reducing Na+ influx and K+ secretion (increasing serum K+ levels), include triamterene and amiloride, often combined with other therapies, SEs= hyperkalemia, metabolic acidosis and dry eye

Aldosterone

Steroid hormone produced by the adrenal cortex that increases sodium reabsorption/potassium secretion in principal cells by increasing the number of ENaC channels

Spironolactone

Aldosterone receptor antagonist that blocks aldosterone-mediated gene transcription, used for hyperaldosteronism, edema from CHF, and hypokalemia

Antidiuretic hormone (ADH)

Hormone that increases water reabsorption in the collecting duct by inserting aquaporin-2 into the apical membrane of principal cells (and aquaporin-3 into basolateral to allow water to enter interstitium)

V2 receptor

ADH receptor on principal cells that activates cAMP signaling leading to aquaporin insertion

ADH Urea effects

Increases urea permeability in inner medullary collecting duct by inserting urea transporters into the apical membrane (by activating adenyl cyclase and PKA)