Obligatory Reabsorption And Secretion In The Proximal Convoluted Tube

Question 1

Na+ Tubular Transport

Answer 1

• Low Na+ inside cell maintained by Na+/K+ ATPase on the basolateral membrane. Extrudes Na+ back to blood. K+ leads to blood. Generates gradient for Na+ to enter via apical membrane. Transcellular route requires vhannels/transporter. Other molecules are reabsorbed using this gradient.
• Transcellular Transport via apical Na+/H+ exchanger and many apical Na+ co-transporters. Exits towards blood via the basolateral Na+/K+ ATPase.
• Paracellular Transport via “leaky” tight junctions - neary 2/3 of Na+ reabsorbed via transcellular pathways will leak back to lumen through paracellular pathway.

Question 2

H+ Tubular Transport

Answer 2

• H+ can enter the cell via co-transport with amino acids. Or can be made in the cell when H2CO3 is acted upon by Carbonic Anhydrase creating H+ and HCO3-.
• H+ exits cell through apical Na+/H+ exchanger.

Question 3

K+ Tubular Transport

Answer 3

K+ enters cell via basolateral Na+/K+ ATPase. No apical entry.

K+ exits cell via basolateral leak K+ channel towards blood. The Cl-/K+ Co-transporter also allows exit of K+ towards blood.

K+ in lumen is predominantly transported back to the blood via the paracellular pathway.

Question 4

Cl- Tubular Transport

Answer 4

• Cl- is transported partly via a transcellular route: Enters via Apical Cl-/HCO3- Exchanger and Basolateral HCO3-/Cl- Exchanger. Exits via Basolateral Cl- Channel and Basolateral Cl-/K+ Co-transporter.
• Also transported via Paracellular Pathway, dominant route for Cl- in proximal tube, transcellular is dominant in later portion of tube.

Question 5

HCO3- Tubular Transport

Answer 5

• HCO3- couples to the H+ gradient in lumen caused by Na+/H+ Exchanger. Converted to H2O and CO2 via Carbonic Anhydrase. CO2 diffuses into cell. H2O enters cell via aquaporin channels (can also travel via paracellular pathway). H+ is then extruded across apical membrane by Na+/H+ Exchanger.
• HCO3- inside the cell is extruded by the basolateral membrane by Na+/HCO3- Co-transporter and HCO3-/Cl- Exchanger.
• Some HCO3- in the cell will be extruded through the apical membrane back to the lumen via the Apical HCO3-/Cl- Exchanger.
• Luminal HCO3- couples with H+ and is converted to H2O and CO2 to enter the cell again.

Question 6

Ca2+ Tubular Transport

Answer 6

• Ca2+ is freely filtered and reabsorbed, but not secreted.
• 20% via transcellular pathway via Apical Ca2+ Channel, Basolateral Na+/Ca2+ Exchanger and a Basolateral Ca2+ ATPase.
• 80% via paracellular pathway through tight junctions.
• Large share of Ca2+ excretion takes place in the faeces.

Question 7

Mg2+ Tubular Transport

Answer 7

Paracellular Solvent Drag

Question 8

Amino Acid Tubular Transport

Answer 8

• Secondary active transport
• Couple to the Na+ gradient generated by the Na+/K+ ATPase pump.
• Amino acods cross the apical membrane via co-transport with either Na+ or H+.
• Extruded by basolateral uniporters.

Question 9

Monosaccharide Tubular Transport

Answer 9

• Secondary active transport
• Couple to the Na+ gradient generated by the Na+/K+ ATPase pump.
• Crosses the apical membrane via a Na+/Glucose Co-transporter (SGLT1 and SGLT2).
• Extruded across basolateral membrane by GLUT1, a uniporter.

Question 10

Solvent Drag

Answer 10

• The osmotic gradient generated by ions being reabsorbed from the tubule lumen back to the blood (peritubular capillaries) enables paracellular transport of H2O.
• The movement of H2O carries some of the solutes/ions with it, SOLVENT DRAG. Ions are dragged against electrochemical gradient through leaky tight junctions.
• Na+, Cl-, Ca2+, Mg2+, K+, urea.

Question 11

Transport Maximum (Tm)

Answer 11

• The maximal amount of a substance (in mg) which can be transported (reabsorbed or secreted) by tubular cells /min.
• E.g. the rate of reabsorption can become saturated and will not transport anymore, even if more could move. If it can’t mive, it will build up (more will be excreted or more will remain in blood).
• Examples include Glucose (100% reabsorbed from filtrate, not secreted) and Para-Aminohippuric Acid (PAH; not reabsorbed, fully secreted).
• The Tm for glucose reflects the point at which all nephrons have reached maximum capacity to reabsorb glucose.

Question 12

Renal Threshold

Answer 12

The concentration of a substance dissolved in the blood above which the kidneys begin to remove it into the urine.

Question 13

Consequences of Renal Threshold being Exceeded?

Answer 13

Excess glucose appears in urine e.g. glucosuria like in diabetes mellitus.

Question 14

Renal Clearance

Answer 14

-Renal clearance reflects the ability of the kidneys to remove molecules from blood plasma by excreting them into the urine.
-Determined by glomerular filtration, tubular reabsorption and tubular secretion.
- Us X V
Cs = —————
Ps

Question 15

Filtration Fraction (FF)

Answer 15

FF = GFR/RPF

Question 16

Use of Inulin in determining GFR

Question 17

Water Transport in Proximal Tube

Answer 17

• Transcellular via apical water channels (aquaporins), high density in membrane. Dominant route.
• Paracellular via “leaky” tight junctions. Will also follow osmotic gradient generated by e.g. transcellular Na+ reabsorption.

Question 18

Clearance Ratio

Answer 18

-If rates of GFR (clearance of inulin) and renal excretion of substance are known. Possible to calculate if there is a net reabsorption or net secretion of a substance. This is called a clearance ratio.
-Clearance ratio = Uphos Uin
——— / ———
Pphos Pin
-If = 1, substance neither secreted nor reabsorbed. If >1, substance is secreted. If <1, substance is reabsorbed.