Reabsorption & Secretion: A Trip Down The Tubule
Lecture given:
Table of Contents
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Objectives
Describe how reabsorption of solute and water from the tubule into the bloodstream and secretion of solutes from the bloodstream into the tubule are key aspects of nephron function
- Ultrafiltrate has similar content as plasma but without protein
- Normally, ~150-180 litres/day of ultrafiltrate is formed, but we need to conserve essential nutrients and solutes while removing toxic wastes
- >99% of filtered sodium salts and water are reabsorbed
Substance | Urine/Plasma Ratio |
---|---|
Glucose | 0 |
Sodium | ~1 |
Urea | ~60 |
Creatinine | ~150 |
List the various components of the renal tubule and how they function to help generate urine
Na/K/ATPase | H2O | Ions | Glucose, AA, protein | Uric acid, Creatinine, drugs | Diuretic | Histology | Mutation | |
---|---|---|---|---|---|---|---|---|
PCT | yes | reabs | reabs | reabs | secrete | CI | 15mm; Dark cytosol, small lumen | Fanconi's |
Thin loop (D) | little | highly reabs | little | no | no | N/A | 2-14mm; epithelial cells like sunny side up eggs | |
Thin loop (A) | yes | NO | passive reabs | no | no | N/A | ||
TAL | yes | NO | NaCl reabs, X2+ reabs | no | no | Loop | 12mm; Thicker cells, larger nucleus | Bartter's |
DCT | yes | no? | Ca2+ reabs, Cl reabs | no | no | Thiazide | 5mm; lighter cytosol, larger lumen | Gitelman's |
CD (p) | yes (aldo) | yes (ADH + Aldo) | reabs K or Cl | no | no | K sparing | 20mm; Cell divisions visible due to interdigitation | |
CD (α) | yes | no | H secretion | no | no | N/A |
- glomerular capillaries have fenestrations that make them ~5000 times more permeable than brain
- ~25% of cardiac output are diverted to renal blood flow (RBF)
- renal plasma flow = (1-hct)(RBF)
- GFR = ~20% of renal plasma flow
- Most of the reabsorption/secretion is driven by gradients and Na/K/ATPase
Legend
Out of lumen; Into lumen
Proximal Tubule
- Symporter: HCO3-, only place for Glucose, AA, Phosphate, and vitamins absorption
- Anteporter: H+, NH4+
- Important process: H2O -> H+ + OH-; OH- + CO2 --Carbonic Anhydrase--> HCO- (vasa recta)
- No anteporter/symporter: Organic cations and anions (e.g. urate, creatinine, drugs)
Thin Loop of Henle
- 2-14 mm long depending on location of the nephron
- Descending: very little Na/K/ATPase, so very little salt movement, but highly permeable to water
- Ascending: Impermeable to water, highly permeable to salt
Thick Ascending Limb
- 12 mm long, pass near afferent arteriole where the macula densa form the juxtaglomerular apparatus
- Symport: Na, K, Cl (loop diuretics)
- Channel: K
- NO water absorption
- Absorbs ~30% of filtered NaCl
- K back leak causing urine to be positively charged, and will push X2+ and cations through paracellular spaces
- Therefore, loop diuretics will cause calcium loss in the urine
Distal Convoluted Tubule
- ~5mm long
- Symporter: Cl (Thiazides)
- Channels: Ca -> Ca+Vit D
- Basal side has Na/Ca anteporter to put Ca into vasa recta
- Major site of Ca absorption via calcium channel, and combine with Vitamin D-induced Ca binding protein
- Cl sensor in cell to control activity of symporter
- If lots of Cl in cell, means there's lots of Na in cell too through the symporter. Ca will be repelled and not come through the channel as easily.
- Thiazides can be used to treat kidney stones by inhibiting the symporter to increase Ca absorption
Collecting Ducts
- Coalescence of many DCTs
- ~20 mm, emput into renal pelvis
- Principal cells:
- Na move through channels will repel K to move through channels, and Cl can move paracellularly
- Aquaporins can be inserted via ADH to modify water content of urine
- Aldosterone binds to Aldosterone receptors in the nucleus by entering from the basal side (Spironolactone) and increase the activity of the Na channel. ANP decreases its activity
- α-intercalated cells: H+ channels and K & H anteporters are important for acidfying urine (pH ~6)
- Movement of Na from principal cells out of the urine will attract H+ into the urine
- Things interfering with principal cell function will cause hyperkalemia AND renal tubular acidosis
Counter-current Exchange
- The descending and ascending limbs of Henle are next to each other
- From the PCT, the filtrate is still pretty dilute, but the interstitium is already concentrated due to vasa recta carrying away the water
- Since the descending limb is impermeable to salt, it lets only water out into the concentrated interstitium
- When the filtrate gets to the bottom of the loop, the osmolality can be as high as 1200 mOsm/L, as concentrated as the interstitium (diffusion)
- Then the ascending limb will allow salt to move into the interstitium (first passively, then active secretion)
- By the time the filtrate gets to the collecting duct, the filtrate can be only 50 mOsm/L
- In the collecting duct, urea can also move into the interstitium to concentrate urine, and urine can be concentrated or diluted depending on the presence of aquaporins
- So, the urine can have a range of concentration 50-1200 mOsm/L
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page revision: 39, last edited: 15 Apr 2012 05:37