Tubular reabsorption

- The second step of urine formation

- Very selective, quantitatively large and variable process
- Needed to maintain the composition of the ECF
- Glucose and amino acids are almost completely reabsorbed
- 99% of water and 99.5% of salt are reabsorbed

- Substances are reabsorbed by being transported first across the tubular

epithelial wall into the interstitial fluid then into the blood
- Bulk flow: flow from the interstitial fluid to the peritubular capillaries
- Each tubular epithelial cell has two membranes:
 The luminal (apical) membrane faces the tubular lumen
 The basolateral membrane lies in contact with the interstitial fluid

- Substances can be transported through one of the two routes

 Transcellular: across the tubular epithelium through special carriers
 Paracellular: across leaky junctions between the tubular cells
- Water moves by osmosis through aquaporin channels found on the
basolateral and luminal membrane or sometimes between the cells

- Active transport
 Primary:
 Transport is coupled directly to an energy source
 Reabsorption of Na by Na-K pump
 Secondary:
 Coupled to an energy source in an indirect way
 Reabsorption of glucose and amino acids
 Co-transport: movement to the same direction
 Counter-transport: movement to opposite directions

- Active transport of sodium through the tubular membrane

 Takes place in all segments except descending limb of Henle
 Of the Na+ filtered, 99.5% is normally reabsorbed
 Of the Na+ reabsorbed, on average
 67% in the proximal tubule
 25% in the loop of Henle
 8% in the distal and collecting tubules (depends on hormones)
 Mostly mediated by Na+/K+ ATPase pump on basolateral membrane
 This pump keeps Na concentration low in tubular cells and high in the ISF
 Water follows reabsorbed sodium by osmosis
 Thus, sodium reabsorption has a main effect on blood volume and BP
 Aldosterone promotes Na retention by
  Insertion of additional Na channels into the luminal membrane
 Insertion of additional Na/K pumps into basolateral membrane
 This insertion takes place in the distal and collecting tubules

 Atrial Natriuretic Peptide “ANP” (from heart) decreases Na reabsorption

- Water and chloride reabsorption

 Na reabsorption stimulates water and chloride to pass passively
 Water follows the reabsorbed sodium, by means of osmosis, and this
creates an increase in the luminal concentration of chloride
 Therefore, providing chemical gradient for chloride ions

- Urea reabsorption
 Occurs through urea transporters, in the descending
limb and first part of ascending limb of loop of Henle
and the last part of the collecting duct
 When water and sodium reabsorbed in the proximal
tubule, urea becomes more concentrated
 This will create a concentration gradient favoring the
reabsorption of urea
 Urea becomes more concentrated in the last part of
the collecting duct, which is important to create
hyperosmolar medullary interstitium
 Then urea is picked up again by the loop of Henle

Renin-Angiotensin-Aldosterone-System
- Any ↓ in NaCl, ECF or BP stimulates kidneys to release renin
- Renin converts angiotensinogen into angiotensin I (synthesized by liver)
- Angiotensin I is converted to angiotensin II by the "ACE" (in lungs)
- Angiotensin II functions
 Stimulates zona glomerulosa of adrenal cortex to release aldosterone
 Vasoconstriction of the efferent arterioles
 Stimulation of thirst center and vasopressin release

Transport Maximum "Tm" for actively reabsorbed substances

- Happens due to saturation of the carriers
- Determined primarily by the number of transporters
- Tm for Na in proximal tubules does not exist (gradient-time transport)
 - This principle also applies to the substances that are actively secreted
 Creatinine (16mg/min)
 Para-aminohippuric acid "PAH" (80mg/min)

- Passively-transported substances do not exhibit a Tm and they depend on

 Electrochemical gradient
 Permeability of the membrane for the substance
 Time that the fluid containing the substance remains within the tubule

- The substances that follow Tm transport also have a renal threshold

- If this threshold exceeded, the substance starts to appear in urine

- For glucose
 Tmax is 375mg/dl
 Renal threshold for glucose is 200 mg/dL
 Some nephrons excrete glucose in a lower than transport maximum level

Reabsorption and Secretion along different parts of the nephron:

- Proximal tubule
 Most of the reabsorption (65%) of all substances happens in the PCT
 High capacity for active and passive reabsorption
 The proximal tubule epithelial cells
 Highly metabolic
 Have large numbers of mitochondria
 Extensive brush borders on the luminal membrane
 In the 1st half Na is reabsorbed by co-transport with glucose and AAs
 In the 2nd half Na is reabsorbed mainly along with chloride ions
 Certain substances, such as hydrogen, organic acids (Bile salts, oxalate,
catecholamine and urates), and bases (HCO3-) are actively secreted
 Concentration of solutes along the PCT
 Concentration of substances that are
completely reabsorbed, such as glucose &
amino acids, will drop
 Concentrations of sodium and chloride remain
relatively constant, that’s because of the water
permeability
 Some substances, such as creatinine and urea,
are less permeable and not actively
reabsorbed, and their concentration increases
- Loop of Henle:
 Consists of three functionally and structurally distinct segments:
 The thin descending segment
 The thin ascending segment
 The thick ascending segment
 The thin segment
 Doesn't contain sodium or solute transporter
 Highly permeable to water
 Important in generation of hyperosmolar medullary interstitium
 The thick ascending segment
 Contains large number of mitochondria and sodium transporters
 Providing high capacity for sodium transport
 Other cations can pass through the paracellular route
 Two carriers for sodium reabsorption at the luminal membrane
 Na+/H+ carrier:
 Moves sodium ions to inside the cell
 Moves hydrogen ions to the tubular lumen
 Na+/2Cl-/K+ co-transporter:
 Uses the potential energy released by the downhill
diffusion of Na into cell to drive the reabsorption of
potassium against a concentration gradient
 Can be inhibited by the loop diuretics
 Then sodium inside the cells moves to the interstitial fluid through
the Na+/K+ ATPase pump
 Potassium in the cells can diffuse back into either the tubular
lumen or the interstitial fluid

- Distal Tubule
 The very first portion forms part of the juxtaglomerular complex
 The next part is highly convoluted
 Same characteristics of thick segment of ascending limb of loop of Henle
 Reabsorbs most of the ions, including sodium, potassium, and chloride
 Impermeable to water and urea
 Referred to as the diluting segment because it dilutes the tubular fluid
 Na and Cl move from lumen into the cell by the Na+/Cl- co-transporter
 Then sodium will be transported to the interstitial fluid via Na/K pump
 Chloride follows sodium through Cl channels
 Na/Cl channels can be inhibited by Thiazide
- Principal cells
 In the late distal tubule and collecting tubule
 Responsible for the reabsorption of sodium, chloride and water
 Responsible for the secretion of potassium
 Under the hormonal control of Aldosterone and ADH
 ADH works only on principle cells of the collecting duct
 Depend on the activity of Na/K pump in cell’s basolateral membrane
 The primary sites of action of the potassium-sparing diuretics
 Aldosterone antagonists inhibit the stimulatory effects
of aldosterone on sodium reabsorption and potassium
secretion
 Sodium channel blockers
 Directly inhibit the entry of sodium into the
sodium channels of the luminal membranes
 Reduce the amount of sodium that can be
transported across the basolateral membranes
by the sodium-potassium ATPase pump

- Intercalated cells
 Avidly Secrete Hydrogen and Reabsorb Bicarbonate and Potassium Ions
 Around 40% of cells in the late distal tubule and collecting ducts
 Type A
 Secretes hydrogen ions by the
 H+ ATPase transport system
 H+/K+ ATPase transporter
 Hydrogen is generated in this cell by the
action of carbonic anhydrase on water and
carbon dioxide to form carbonic acid
 Carbonic acid dissociates into hydrogen ions
and bicarbonate ions
 Hydrogen ions are then secreted into tubules
 For each hydrogen ion secreted, a bicarbonate
ion becomes available for reabsorption across
 These cell are important in acidosis

 Type B
 Functions opposite to those of type A cells
 Secretes bicarbonate and reabsorb hydrogen in alkalosis
 Has hydrogen and bicarbonate transporters located in the
opposite sides compared to those in type A cells
 Hydrogen ions are actively transported out of the cell on the
basolateral side of the cell membrane by hydrogen ATPase
  Bicarbonate is secreted into the lumen thus eliminating excess
plasma bicarbonate in cases of alkalosis

- Medullary collecting duct

 Reabsorb less than 10 per cent of the filtered water and sodium.
 The final site for processing the urine.
 Play important role in determining final urine output of water & solutes.
 Its permeability to water is controlled by the level of ADH.
 The medullary collecting duct is permeable to urea.
 Some of the tubular urea is reabsorbed into the medullary interstitium
 Helping to raise the osmolality in this region of the kidneys
 Contributing to the kidneys’ ability to form a concentrated urine
 Capable of secreting hydrogen ions against a large concentration
gradient, as also occurs in the cortical collecting tubule.
 Plays a key role in regulating acid-base balance.