Lecture 15: proximal tubule reabsorption & secretion Flashcards
what is reabsorption?
the movement of a substance from the fluid of a tubular lumen (from the nephron) into the peritubular capillary (back into circulation / blood)
what does the proximal tubule contain? what effect does this structure have ?
- the luminal surface contains a brush border (ie microvilli)
- the presence of microvilli greatlt increase the SA available for absorption
what does the proximal tubule reabsorb?
- Na+ (65 approx %)
- Cl- (65 approx %)
- Glucose (virtually all)
- protein / amino acids (virtually all)
- HCO3-
- water (absorbed via osmosis along with solutes)
what are the** 2 sides **of the promixmal tubule epithelial cell?
- the luminal side - in contact with the lumen - the fluid etc
- the basolateral side - in contact with the interstitial fluid
what are the 2 types of transport methods of solute transport across the epithelial barrier?
- paracellular transport (through tight junctions between the cells)
- transcellular transport (through the cell via channels/ transporters)
what is important to mention about Na+ entry into the epithelial cell of the PCT?
- 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
By what transporter does Na+ mainly enter the cell?
- most of the Na+ entering the tubule cell does so in exchange for H+ secretion using a transporter called NHE3 (Na-H-exchanger 3)
what transporter / ATPase pump is located on the basolateral side of the tubule cell?
- the NA+K+ATPase pump
How does Na+ leave the proximal tubule cell?
- through the Na+/K+/ATPase pump
- it is actively transported against its concentration gradient
Along the first half of the proximal tubule, how does Na+ get reabsorbed?
* 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
How is glucose reabsorbed in the first half of the PCT?
- 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
why does the [Cl-] in the tubular fluid increase?
- more water is being reabsorbed than Cl- , due to osmosis (rememeber h20 flows from low to high solute conc)
- there is a higher preferance for Na+ and HCO3- reabsorption in the 1st half of the PCT, rather than Na+ and Cl-
Along the 2nd half of the proximal tubule, how are Na+ and Cl- reabsorbed?
- 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
Other than the transcellular route, what is the other method by which Cl- is reabsorbed?
- 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-)
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?
SGLT1 symporter
Discuss water reabsorption in the PCT
- 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
what is tubular secretion?
- a process that moves substances from the peritubular capillaries into the tubular lumen
Explain the difference between reabsorption and secretion
*** 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
what does the proximal tubule secrete?
- 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**
what is a very important function regarding secretion?
- it is essential in limiting the body’s exposure to toxic compounds
By what main mechanism does secretion occur?
* transcellular mechanisms via transporters and channels etc
* not via paracellular mechanisms because organic compounds are not significantly permeable through tight junctions
Describe the secretion of organic anions (OA-) across the PCT
- Na gradient (low intracellular Na+) is generated by the basolateral Na+/K+/ATPase pump
- basolateral OAT antiporters move anions (-) into the cell in exchange for endogenous dicarboxylic acids (eg alpha-ketaglurate)
- alpha ketaglurate is actively moved into cells via NADC3 (Na+ dicarboxylate acid) symporters - using the energy derived from Na+/K+ ATPase pump
- anions are transported into the tubular lumen across the **apical membrane by OAT and MRP proteins **
Describe organic cation (OC+) secretion
- 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