SM_191a: Functions of the Renal Tubule I

Question 1

Proximal tubule has __ major subdivisions

Answer 1

Proximal tubule has 3 major subdivisions

Question 2

_____ of the proximal tubule dramatically increase surface area to increases rates of reabsorption

Answer 2

Microvilli (brush border) of the proximal tubule dramatically increase surface area to increases rates of reabsorption

Question 3

Proximal tubule has _______ epithelia

Answer 3

Proximal tubule has leaky epithelia (low resistance)

(paracellular is main route of reabsorption)

Question 4

______ is the main process by which fluid moves in the proximal tubule

Answer 4

Convection is the main process by which fluid moves in the proximal tubule

• Hydrostatic pressure, which opposes reabsorption, is low in the proximal tubule
• Oncotic pressure, which favors reabsorption, is high in the proximal tubule
• Net effect is to favor fluid movement back into capillary (reabsorption)

(also parallel reabsorption of Na⁺ creates transient increase in osmolality, causing water be reabsorbed)

Question 5

Difference between ______ and ______ is the driving force for filtration

Answer 5

Difference between hydrostatic pressure and oncotic pressure is driving force for filtration

Question 6

Describe glomerulotubular balance

Answer 6

Glomerulotubular balance

• In the glomerular capillary, hydrostatic pressure is first greater than oncotic pressure (favoring filtration) but then the two become equal
• In the peritubular capillary, oncotic pressure is greater than hydrostatic pressure (favoring reabsorption)

Question 7

In the glomerular capillary, _____ is first greater than _____, favoring _____, but then the two become equal

Answer 7

In the glomerular capillary, hydrostatic pressure is first greater than oncotic pressure, favoring filtration, but then the two become equal

Question 8

In the peritubular capillary, ______ is greater than ______, favoring ______

Answer 8

In the peritubular capillary, oncotic pressure is greater than hydrostatic pressure, favoring reabsorption

Question 9

Describe what happens if efferent arteriole is constricted

Answer 9

Efferent arteriole constricts

1. Hydrstatic pressure in glomerular capillary increases
2. GFR increases
3. Glomerulotubular balance: force of glomerular reabsorption increases in response

Question 10

In the proximal tubule, _____, _____, _____, _____, and _____ bring Na⁺ across the apical membrane into the cells from the lumen

Answer 10

In the proximal tubule, Na⁺/H⁺ antiporter, Na⁺/glucose symporter, Na⁺/amino acid symporter, 2-3Na⁺/phosphate symporter, and Na⁺/solute symporter bring Na⁺ across the apical membrane into the cells from the lumen

(mainly Na⁺/H⁺ antiporter)

Question 11

In the proximal tubule, ______ and ______ bring Na⁺ across the basolateral membrane into the interstitium from the cells

Answer 11

In the proximal tubule, Na⁺/K⁺ ATPase and Na⁺/3HCO₃^- symporter bring Na⁺ across the basolateral membrane into the interstitium from the cells

(Na⁺/K⁺ ATPase leaves a negative charge inside the cell)

(bicarbonate is driving force for Na⁺/3HCO₃^- symporter)

Question 12

In the proximal tubule, Na⁺ travels from _____ to _____ to _____

Answer 12

In the proximal tubule, Na⁺​ travels from lumen to cells to interstitium (reabsorption)

Question 13

In the proximal tubule, Cl^- crosses the apical membrane to enter the cells from the lumen using the ______

Answer 13

In the proximal tubule, Cl^- crosses the apical membrane to enter the cells from the lumen using the formate/Cl^- antiporter

(formate diffuses into cell to maintain gradient for formate/Cl^- antiporter)

Question 14

In the proximal tubule, Cl^- crosses the basolateral membrane to enter the interstitium from the cells using the _____

Answer 14

In the proximal tubule, Cl^- crosses the basolateral membrane to enter the interstitium from the cells using the K⁺/Cl^- symporter

(K⁺ high inside the cell)

Question 15

In the proximal tubule, Cl^- travels from the _____ to _____ to _____

Answer 15

In the proximal tubule, Cl^- travels from the lumen to cells to interstitium (reabsorption)

Question 16

In the proximal tubule, H₂O travels from lumen to cells and from cells to interstitium using ______

Answer 16

In the proximal tubule, H₂O travels from lumen to cells and from cells to interstitium using aquaporin 1 (reabsorption)

(most water is still reabsorbed by force of convection through paracellular pathway)

Question 17

____, ____, ____, and ____ are _____ in the proximal tubule

Answer 17

Na⁺, Cl^-, H₂O, and amino acids are reabsorbed in the proximal tubule

Question 18

Describe the mechanism of HCO₃^- reabsorption in proximal tubule

Answer 18

HCO₃^- reabsorption in proximal tubule

• Bicarbonate is converted to carbonic acid which is then converted to CO₂ by carbonic anhydrase in lumen and then crosses apical membrane
• Inside cell, CO₂ is converted back into carbonic acid by carbonic anhydrase and then dissociates into HCO₃^- and H⁺
• HCO₃^- crosses basolateral

Question 19

At the physiological end of bicarbonate concentration, the bicarbonate transporter in the proximal tubule is _____ and some bicarbonate _____

Answer 19

At the physiological end of bicarbonate concentration, the bicarbonate transporter in the proximal tubule is saturated and some bicarbonate escapes to be filtered

(transport maximum: proximal tubule has ceiling above which it cannot reabsorb more bicarbonate)

Question 20

Describe the mechanism of glucose reabsorption in the proximal tubule

Answer 20

Glucose reabsorption in the proximal tubule

• Na⁺/glucose symporter brings glucose into cells across apical membrane
• Glucose goes to interstitium across basolateral membrane via transporter

Question 21

______ block the Na⁺/glucose symporter in the apical membrane of the proximal tubule

Answer 21

SGLT2 inhibitors block the Na⁺/glucose symporter in the apical membrane of the proximal tubule

(canagliflozin)

(allow glucose to be excreted)

Question 22

Na⁺/glucose symporter can be ______ after certain level of plasma glucose

Answer 22

Na⁺/glucose symporter can be saturated after certain level of plasma glucose

(glycosuria: high blood sugar spills into urine)

Question 23

Describe the mechanism of ammonium secretion in the proximal tubule

Answer 23

Ammonium secretion in the proximal tubule

• In cells, lutaminase converts glutamine to NH₃ and glutamate
• NH₃ crosses apical membrane into lumen
• NH₃ is protonated in lumen to form NH₄⁺ (proton trapping)
• NH₄⁺ is secreted

(NH₃ is uncharged and lipid soluble, when protonated cannot cross apical membrane and is secreted)

Question 24

______ is the site of secretion of drugs or metabolites through ______

Answer 24

Proximal tubule is the site of secretion of drugs or metabolites through organic cation transporters and organic anion transporters

(enter cells from interstitium via organic cation transporters and organic anion transporters)

Question 25

Organic cation transport brings ______ and ______ across basolateral membrane to the ______

Answer 25

Organic cation transport brings cimetidine and creatinine across basolateral membrane to the cells

(then go to lumen through p-glycoprotein and MRP2 and then are secreted)

Question 26

Organic anion transport brings ______ and ______ across basolateral membrane to the ______

Answer 26

Organic anion transport brings pencillin and uric acid across basolateral membrane to the cells

(then go to lumen through MRP2/MRP4/ABCG2 and then are secreted)

Question 27

Amino acid _____ occurs in the proximal tubule

Answer 27

Amino acid reabsorption occurs in the proximal tubule

(amino acids can only cross basolateral membrane to go to the interstitium, transporters exist for groups of amino acids, important for inborn errors of metabolism such as cystinuria)

Question 28

In absorptive endocytosis in the proximal tubule, _____

Answer 28

In absorptive endocytosis in the proximal tubule, endosome with protein enters cell, is acidified, and breaks down protein into amino acid

(Dent disease: defect in endosomal acidification due to impairment of chloride channel in endosomes)