Lecture 15: proximal tubule reabsorption & secretion Flashcards

1
Q

what is reabsorption?

A

the movement of a substance from the fluid of a tubular lumen (from the nephron) into the peritubular capillary (back into circulation / blood)

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2
Q

what does the proximal tubule contain? what effect does this structure have ?

A
  • the luminal surface contains a brush border (ie microvilli)
  • the presence of microvilli greatlt increase the SA available for absorption
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3
Q

what does the proximal tubule reabsorb?

A
  1. Na+ (65 approx %)
  2. Cl- (65 approx %)
  3. Glucose (virtually all)
  4. protein / amino acids (virtually all)
  5. HCO3-
  6. water (absorbed via osmosis along with solutes)
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4
Q

what are the** 2 sides **of the promixmal tubule epithelial cell?

A
  • the luminal side - in contact with the lumen - the fluid etc
  • the basolateral side - in contact with the interstitial fluid
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5
Q

what are the 2 types of transport methods of solute transport across the epithelial barrier?

A
  1. paracellular transport (through tight junctions between the cells)
  2. transcellular transport (through the cell via channels/ transporters)
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6
Q

what is important to mention about Na+ entry into the epithelial cell of the PCT?

A
  • the proximal tubule cells have a low intracellular Na+ concentration
  • therefore Na+ movement from the lumen into the cell is down a large electrochemical gradient
  • therefore Na+ entry into the PCT cell occurs passively but it is carrier mediated
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7
Q

By what transporter does Na+ mainly enter the cell?

A
  • most of the Na+ entering the tubule cell does so in exchange for H+ secretion using a transporter called NHE3 (Na-H-exchanger 3)
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8
Q

what transporter / ATPase pump is located on the basolateral side of the tubule cell?

A
  • the NA+K+ATPase pump
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9
Q

How does Na+ leave the proximal tubule cell?

A
  • through the Na+/K+/ATPase pump
  • it is actively transported against its concentration gradient
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10
Q

Along the first half of the proximal tubule, how does Na+ get reabsorbed?

A

* low intracellular Na+ is maintained by the Na+/K+/ATPase pump
* Na+ moves down its conc gradient via the **NHE3 transporter **- which in turn provides energy for the secretion of H+ from the cells into the tubular lumen
* the hydration of of intracellular CO2- H2CO3 generates H+ and HCO3- (bicarbonate) in the cell
*** HCO3- & Na+ leaves **the cell via a **Na+-HCO3- symporter **
* Na+ also gets effluxed out of the cell via the Na+/K+/ATPase

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11
Q

How is glucose reabsorbed in the first half of the PCT?

A
  • the reabsorption of glucose is **Na+ dependent **
  • SGLT2 symporter uses the energy generated by the basolateral Na+/K+/ATPase pump to transport both Na+ and glucose into the cell - IE **secondary active transport **
  • glucose then leaves the cell via GLUT2 uniporter and the glucose uniporter and goes into the IF
  • it then gets reabsorbed into the peritubular capillaries
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12
Q

why does the [Cl-] in the tubular fluid increase?

A
  1. more water is being reabsorbed than Cl- , due to osmosis (rememeber h20 flows from low to high solute conc)
  2. there is a higher preferance for Na+ and HCO3- reabsorption in the 1st half of the PCT, rather than Na+ and Cl-
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13
Q

Along the 2nd half of the proximal tubule, how are Na+ and Cl- reabsorbed?

A
  • Na+ and Cl- enter the cell via the Na+-H+ antiporters and** Cl- anion transporters**
  • inside the proximal tubule cell, H+ ions and an anion (- ion) dissociate and get recycled back across the apical membrane
  • Na+ leaves the cell via the Na+/K+/ATPase pump
  • Cl- leaves the cell and enters the blood via the** K+-Cl- symporter **on the basolateral membrane
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14
Q

Other than the transcellular route, what is the other method by which Cl- is reabsorbed?

A
  • as Cl- permeability is greater than that of other anions in the final 2 thirds of the PCT
  • Cl- is reabsorbed paracellularly down its concentration gradient (as there is high tubular conc of Cl-)
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15
Q

In comparison to the SGLT2 symporter for Na+ and glucose in the first half of the proximal tubule, what transporter is present on the apical surface of the 2nd half of the PCT?

A

SGLT1 symporter

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16
Q

Discuss water reabsorption in the PCT

A
  • the proximal tubule is highly permeable to water
  • both the apical and basolateral membranes of the proximal tubule cells express aquaporins
  • also,water can also move between cells (ie paracellularly) through solvent drag
17
Q

what is tubular secretion?

A
  • a process that moves substances from the peritubular capillaries into the tubular lumen
18
Q

Explain the difference between reabsorption and secretion

A

*** direction of transport is different **
* secretion moves substances from the peritubular capillaries into the tubular lumen
* reabsorption is movement from the tubule lumen into the peritubular capillaries

19
Q

what does the proximal tubule secrete?

A
  • secretes a large variety of organic cations and anions that are** products of metabolism**
  • it also secretes numerous exogenous compounds (substances that dont belong in the body) eg** drugs and toxic chemicals**
20
Q

what is a very important function regarding secretion?

A
  • it is essential in limiting the body’s exposure to toxic compounds
21
Q

By what main mechanism does secretion occur?

A

* transcellular mechanisms via transporters and channels etc
* not via paracellular mechanisms because organic compounds are not significantly permeable through tight junctions

22
Q

Describe the secretion of organic anions (OA-) across the PCT

A
  1. Na gradient (low intracellular Na+) is generated by the basolateral Na+/K+/ATPase pump
  2. basolateral OAT antiporters move anions (-) into the cell in exchange for endogenous dicarboxylic acids (eg alpha-ketaglurate)
  3. alpha ketaglurate is actively moved into cells via NADC3 (Na+ dicarboxylate acid) symporters - using the energy derived from Na+/K+ ATPase pump
  4. anions are transported into the tubular lumen across the **apical membrane by OAT and MRP proteins **
23
Q

Describe organic cation (OC+) secretion

A
  • apical transport of the organic cation is also driven by the energy generated by Na+/K+/ATPase pump
  • cations are transported across the basolateral membrane by** passive diffusion via or different OCT proteins **
  • the sodium gradient** drives H+ out of the cell** via the Na+-H- antiporter 3 (NHE3)
  • apical OCTN proteins move small cations out of the cell in exchange for H+
  • larger cations are transported into the tubular lumen via MDR1 ATPase