DSF - 11-17-11 - Physiology - Solute Handling Along Tubules

1. Apical/Luminal side
- Faces tubule

2. Basolateral/Serosal side
- Faces the interstitium and blood vessels

1. Transcellular
- Across and through cells via transport proteins
- Active transport or secondary/coupled active transport

2. Paracellular
- Between cells via leaky gap junctions
- Driven by electrochemical gradients and osmotic forces

Pinocytosis

Diffusion

Solvent drag

Maintaining intracellular Na+ low

Generates driving force for Na+ to enter cells from the tubular lumen

Co-transport via sodium

Occurs exclusively in the proximal tubule

SGLT1 in the early proximal tubule

SGLT2 in later proximal tubule

Transport is driven uphill by the downhill movement of sodium that comes from the gradient created by the Na+/K+ ATPase

GLUT1

GLUT2

Glucose moves passively out of the cell into the interstitium and then passively into the peritubular capillaries

200 mg/dL

OATs are responsible for secreting organic anions into tubular cells from the blood and interstitial space

A low urine pH (full of H+ ions) neutralizes organic anions which can diffuse back across renal cells

A high urine pH favors secretion and excretion of organic anions

2/3 of total reabsorption takes place in the proximal tubule

Isosmotic reabsorption:
- Water and sodium are reabsorbed to the same extent

- Glucose reabsorption (only site)

- 67% of sodium reabsorption

- Organic anion and cation secretion from peritubular capillaries

- Reabsorption of filtered proteins

Symporters that use the DOWNHILL gradient of Na+ (low in the epithelial cell due to the Na+/K+ ATPase) to move these compounds UPHILL from the tubular lumen into the cell

Tubular lumen:
- [Na+] ~ 145 mM
- [K+] ~ 4 mM

Renal epithelial cell:
- [Na+] ~ 30 mM
- [K+] ~ 110 mM

Peritubular capillary:
- [Na+] ~ 145 mM
- [K+] ~ 4 mM

Establishes an osmotic gradient where the concentration of solutes is lower in the tubular lumen than in the interstitium

This enables water to move from the tubular lumen into the interstitium via aquaporins

This creates an isosmotic reabsorption in the proximal tubule

1. Na+/K+ ATPase maintains renal epithelial cell [Na+] low

2. Na+/H+ antiporter on the apical surface moves H+ out of the cell and into the tubular lumen using the downhill gradient of Na+

3. The transported H+ combines with filtered bicarbonate via carbonic anhydrase to yield H20 and CO2 in the tubular lumen

4. H20 and CO2 move from the tubular lumen into the renal epithelial cell via aquaporins and diffusion, respectively

5. H20 and CO2 in the renal epithelial cell combine via carbonic anhydrase to reform H+ and bicarbonate ion

6. Bicarbonate ion is transported out of the cell down its concentration gradient via a symporter that transports Na+ out of the cell against its concentration gradient

7. H+ is recycled and used to drive the antiporter on the apical surface

Bicarbonate is the major physiological buffer

Urine flow would increase

Na+ and H20 are staying behind in the urine

[Cl-] increases because there are no transporters for Cl- and water is being reabsorbed, thus increasing the concentration

1. Cl- ions travel paracellularly from the tubular lumen into the interstitium down their concentration gradient

2. Positive ions (Na+, K+, Ca2+, Mg2+) move paracellularly down their electrical gradient in response to a more positive charge in the tubular lumen

3. H20 moves down its concentration gradient from the tubular lumen into the interstitium due to a decreased osmolality, also causing solvent drag

1. Anions in the proximal tubule combine with H+ ions pumped inot the tubular lumen (via H+/Na+ antiporter) combine to a neutral form and cross into the the renal epithelial cell

2. These neutral molecules then dissociate back into their anion form and are exchanged for Cl- via a symporter on the apical side

1. Osmotic gradient established with reduced osmolality move water from the tubular lumen into the renal epithelial cells and interstitium

2. Starling forces in the interstitium and peritubular capillaries move water from the interstitium into the peritubular capillaries
- Hydrostatic pressure in the interstitium
- Oncotic pressure in the peritubular capillaries

No further glucose can be reabsorbed because the glucose transporters are all saturated

Urine volume would increase

Filtered glucose would exceed the maximum amount of reabsorption and there is less of a drive for water to be reabsorbed from the proximal tubule

Penicillin, an organic anion, would stay in the blood longer because PAH would compete for OATs

1. Organic cations are transported from the blood and interstitium into the renal epithelial cells via organic cation transporters (OCTs) on the basolateral surface

2. Organic cations move from the renal epithelial cell through the apical surface into the proximal tubule lumen via OC+/H+ antiporters

3. Organic cation secretion depends on urine pH:
- Acidic urine traps the cations in the urine
- Basic urine neutralizes the cation and allows it back into the renal epithelial cell

1. Proteins in the urine are endocytosed into the renal epithelial cell via endocytic receptors

2. Proteins are degraded into constituent amino acids in the renal epithelial cell

3. Amino acids are transported out of the cell and into the blood by various amino acid transporters

(Process is saturable)

Establishing the mechanism by which water is saved by creating a hyperosmotic interstitial fluid

Na+, Cl-, and H20 move out of the tubular lumen into the hypertonic interstitium

Na+ and Cl- move out of the tubular lumen

No movement of H2O because of a lack of aquaporins

The thin ascending Loop of Henle allows solute out but does not allow water out

The Na+/K+/2Cl- symporter
- One Na+, one K+ and two Cl- ions bind and flip the symporter, transporting K+ and Cl- UPHILL on the back of the DOWNHILL Na+ gradient

This transporter is electrically neutral (positive sodium plus positive potassium are negated by two negative chlorides)

Water follows the ions moved out of the lumen from the Na+/K+/2Cl- symporter and institutes solvent drag

Ca2+ and Mg2+ are brought along, paracellularly

Na+/K+ ATPase maintains intracellular [Na+] low

Na+/Cl- symporter brings Cl- into the epithelial cell against its concentration gradient using the DOWNHILL gradient of Na+

1. Principal cells

2. Intercalated cells

Principal cells:
- Na+/K+ ATPase maintains intracellular Na+ low

- Electrogenic Na+ channels (eNaC) exchange Na+ into the epithelial cell for K- into the tubular lumen via another transporter on the apical surface

Drugs that interfere with K+ loss from the epithelial cells of the late distal convoluted tubule and increase urine volume

A/α - Acid-secreting

B/β - Base-secreting

Moves protons from the interstitium and peritubular capillaries into the tubular lumen

1. CO2 + H2O combine via carbonic anhydrase to form bicarbonate ion and H+

2. V-type proton ATPase on the apical side (vacuolar-type ATPase) moves proton into the tubular lumen

3. P-type proton ATPase on the apical side (exchange type ATPase) is an antiporter that moves proton into the tubular lumen, exchanging it for K+

4. Bicarbonate ion is transported via a antiporter on the basolateral side for Cl-

Bicarbonate ion is secreted into the tubular lumen and H+ is secreted into the interstitum

1. CO2 + H2O combine via carbonic anhydrase to form bicarbonate ion and H+

2. 2. V-type proton ATPase on the basolateral side (vacuolar-type ATPase) moves proton into interstitium

3. Bicarbonate ion is moved into the tubular lumen via an antiporter that exchanges it with Cl-