66: Proximal Tubule Flashcards
The proximal tubule is the nephron segment mediating ________ of ⅔ of both filtered water and filtered salt. Most of this REABSORPTION is constitutive (not regulated) and may increase only when severely volume _______. PT fluid reabsorption occurs ______ without a change in salt concentration in the 33% of the tubular fluid remaining in the PT. For this to be an isoosmotic process, and equal amount of solute and water must be reabsorbed.
The proximal tubule is the nephron segment mediating REABSORPTION of ⅔ of both filtered water and filtered salt. Most of this REABSORPTION is constitutive (not regulated) and may increase only when severely volume depleted. PT fluid reabsorption occurs isosmotically without a change in salt concentration in the 33% of the tubular fluid remaining in the PT. For this to be an isoosmotic process, and equal amount of solute and water must be reabsorbed.
The proximal tubule mediates reabsorption of most of the ______ solutes filtered from plasma (glucose, AA, vitamins) & bicarbonate & phosphate & sulfate. These solutes appear in the _____ if not reabsorbed by the proximal tubule.
The proximal tubule mediates reabsorption of most of the organic solutes filtered from plasma (glucose, AA, vitamins) & bicarbonate & phosphate & sulfate. These solutes appear in the urine if not reabsorbed by the proximal tubule.
The proximal tubule mediates _____ of most of the organic anions and cations from the peritubular capillaries to the lumenal fluid, where they are excreted into the urine. This is bad because these vitamins are not reabsorbed back into the circulation. If the reabsorptive processes are saturated, then the remaining solutes will appear in the _____. Hence, anything that gets past the proximal tubule, will be in the urine.
The proximal tubule mediates secretion of most of the organic anions and cations from the peritubular capillaries to the lumenal fluid, where they are excreted into the urine. This is bad because these vitamins are not reabsorbed back into the circulation. If the reabsorptive processes are saturated, then the remaining solutes will appear in the urine. Hence, anything that gets past the proximal tubule, will be in the urine.
See pg. 3
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Na+ and Cl- transport across the proximal tubule cell layer may be (1) _____, resulting from uptake across the lumenal membrane and efflux across the basal membrane, or (2) ______, resulting from movement of Na+ and Cl- between cells through tight junctions.
Na+ and Cl- transport across the proximal tubule cell layer may be (1) transcellular, resulting from uptake across the lumenal membrane and efflux across the basal membrane, or (2) paracellular, resulting from movement of Na+ and Cl- between cells through tight junctions.
Transcellular transport of sodium to the basal or lateral side of the interstitial space is done via a sodium concentration gradient that maintains a _____ sodium cocentration within the lumenal membrane via the basolateral Na/K ATPase. The inside negative voltage difference is another driving force for sodium to move into the cell. Thus, there is an _____ gradient. 33% of the sodium that leaves trancellularly, backleaks _____ & is reabsorbed again.
Transcellular transport of sodium to the basal or lateral side of the interstitial space is done via a sodium concentration gradient that maintains a low sodium cocentration within the lumenal membrane via the basolateral Na/K ATPase. The inside negative voltage difference is another driving force for sodium to move into the cell. Thus, there is an electrochemical gradient. 33% of the sodium that leaves trancellularly, backleaks paracellulary & is reabsorbed again.
Transcellular Na+ transport results from passive uptake of Na+ across the apical membrane down a Na+ ________ gradient and _____ efflux of Na+ across the basal and lateral membrane against a Na+ electrochemical gradient.
A lumen ____ transepithelial voltage difference serves to drive a paracellular “backleak” of Na+ in the _____ PT and approximately 33% of Na+ transported transcellularly leaks back into the lumen. In the late PT the transepithelial voltage difference reverses and a lumen positive transepithelial voltage difference serves to drive paracellular Na+ transport from lumen to the ____ space.
See figures on pgs. 4-5
Transcellular Na+ transport results from passive uptake of Na+ across the apical membrane down a Na+ electrochemical gradient and active efflux of Na+ across the basal and lateral membrane against a Na+ electrochemical gradient.
A lumen negative transepithelial voltage difference serves to drive a paracellular “backleak” of Na+ in the early PT and approximately 33% of Na+ transported transcellularly leaks back into the lumen. In the late PT the transepithelial voltage difference reverses and a lumen positive transepithelial voltage difference serves to drive paracellular Na+ transport from lumen to the peritubular space.
The passive uptake of Na+ across the PT apical membrane occurs by transport mechanisms mediating Na+-solute _____ and _______. Multiple, substrate-specific, Na+-solute symporters function in the apical membrane as a pathway for cellular Na+ uptake as well as concentrative accumulation of intracellular solutes such as glucose, amino acids, mono- and dicarboxylates, vitamins, phosphate and sulfate.
The net _____ charge transfer resulting from Na+-solute symport creates a lumen negative transepithelial voltage difference, which drives a paracellular “backleak” of Na+ from the peritubular space into the ______. A Na+-solute antiporter mediates the exchange of _____ Na+ for intracellular H+ across the apical membrane.
The active efflux of Na+ across the PT basal and lateral membrane occurs by primary active transport mediated by a _______ and by secondary active transport mediated by _______ symport.
The passive uptake of Na+ across the PT apical membrane occurs by transport mechanisms mediating Na+-solute cotransport in the same (symport) or opposite direction (antiport). Multiple, substrate-specific, Na+-solute symporters function in the apical membrane as a pathway for cellular Na+ uptake as well as concentrative accumulation of intracellular solutes such as glucose, amino acids, mono- and dicarboxylates, vitamins, phosphate and sulfate.
The net positive charge transfer resulting from Na+-solute symport creates a lumen negative transepithelial voltage difference, which drives a paracellular “backleak” of Na+ from the peritubular space into the lumen. A Na+-solute antiporter mediates the exchange of lumenal Na+ for intracellular H+ across the apical membrane.
The active efflux of Na+ across the PT basal and lateral membrane occurs by primary active transport mediated by a Na+-K+ ATPase and by secondary active transport mediated by Na+- HCO3- symport.
Ions and minerals that need to be _____ in the body are reabsorbed into the peritubular capillaries through active transport, secondary active transport, or transcytosis.
The ions that need to be _____ as waste are secreted from the peritubular capillaries into the nephron to be sent towards the bladder and out of the body. Hence, if you do nothing, things in the peritubular space leave the body.
Ions and minerals that need to be saved in the body are reabsorbed into the peritubular capillaries through active transport, secondary active transport, or transcytosis.
The ions that need to be excreted as waste are secreted from the peritubular capillaries into the nephron to be sent towards the bladder and out of the body. Hence, if you do nothing, things in the peritubular space leave the body.
Transepithelial transport of Cl- in the PT occurs _____ in the early and late proximal tubule as well as transcellularly mediated by uptake at the apical (lumenal) membrane & efflux @ the basolateral membrane in the _____ PT.
Paracellular Cl- transport in the early PT is driven by a lumen _____ transepithelial voltage difference (via repulsion) due to the preferential reabsorption of bicarbonate. Cl- concentration gets high in the lumen and there is a concentration gradient that mediates the _____ efflux of lumenal Cl-. This efflux of Cl- creates a lumen positive diffusion potential which drives the paracellular efflux of sodium in the ____ PT.
Transcellular Cl- occurs only in the late PT. There is _____ uptake of Cl- across the PT apical membrane via chloride-solute antiport. The passive efflux of intracellular Cl- across the basolateral membrane is mediated by a Cl- ____ and by a Potassium chloride ____porter.
Transepithelial transport of Cl- in the PT occurs paracellularly in the early and late proximal tubule as well as transcellularly mediated by uptake at the apical (lumenal) membrane & efflux @ the basolateral membrane in the late PT.
Paracellular Cl- transport in the early PT is driven by a lumen negative transepithelial voltage difference (via repulsion) due to the preferential reabsorption of bicarbonate. Cl- concentration gets high in the lumen and there is a concentration gradient that mediates the passive efflux of lumenal Cl-. This efflux of Cl- creates a lumen positive diffusion potential which drives the paracellular efflux of sodium in the late PT.
Transcellular Cl- occurs only in the late PT. There is active uptake of Cl- across the PT apical membrane via chloride-solute antiport. The passive efflux of intracellular Cl- across the basolateral membrane is mediated by a Cl- channel and by a Potassium chloride symporter.
Proximal Tubule Water Reabsorption:
Most (67%) of the glomerular filtrate is returned to the circulation at the proximal tubule where _____ of tubular fluid occurs without a change in osmolarity (passive). PT transepithelial reabsorption of water is _____ and occurs both between cells (paracellular) as well as across cells (transcellular). The primary driving force for paracellular and transcellular water reabsorption is the small osmotic gradient resulting from _____ solute (primarily Na+ and Cl-) reabsorption across the PT. The general rule, which applies to the proximal tubule, as well as to other succeeding segments of the nephron, is: water reabsorption follows from solute _____ across the tubule epithelia. Tubule solute reabsorption creates sufficient difference in transtubular osmolarlity to drive transcellular and paracellular water reabsorption.
The exceptionally high water permeability (leakiness) of the PT permits a large lumen-to-peritubule movement of water in response to a small osmotic ____. The high transcellular water permeability is due to the presence of water (aquaporin) channels in both the ____ and _____ membrane of PT cells. Most PT transepithelial water reabsorption occurs by the _____ pathway driven osmotically by transcellular solute reabsorption.
Water absorption from the peritubular space into the peritubular capillaries is driven by a net difference in _____ forces spanning the peritubular capillary wall favoring absorption of fluid into the ______ capillaries. Recall the Starling forces are the difference in hydrostatic pressure and osmotic pressure inside and outside the capillary. In the glomerulus, the hydrostatic (push out) _____ the oncotic (pull in) = filtration, but in the peritubular capillaries, this is reversed so that ____ exceeds ____ = reabsorption of water.
The paracellular movement of water from lumen to peritubular space driven by the _____, Na+ transport- dependent increase in osmolarity in the lateral space is observed to entrain and “sweep” Na+ and Cl-
within the flow of fluid between cells in the direction of the peritubular capillary. This remarkable process of entrainment or “sweeping” of paracellular Na+ and Cl- across the cell layer is referred to a solvent _____,
where movement of solvent (water) drags solutes along with it between cells.
Proximal Tubule Water Reabsorption:
Most (67%) of the glomerular filtrate is returned to the circulation at the proximal tubule where reabsorption of tubular fluid occurs without a change in osmolarity (passive). PT transepithelial reabsorption of water is passive and occurs both between cells (paracellular) as well as across cells (transcellular). The primary driving force for paracellular and transcellular water reabsorption is the small osmotic gradient resulting from active solute (primarily Na+ and Cl-) reabsorption across the PT. The general rule, which applies to the proximal tubule, as well as to other succeeding segments of the nephron, is: water reabsorption follows from solute reabsorption across the tubule epithelia. Tubule solute reabsorption creates sufficient difference in transtubular osmolarlity to drive transcellular and paracellular water reabsorption.
The exceptionally high water permeability (leakiness) of the PT permits a large lumen-to-peritubule movement of water in response to a small osmotic gradient. The high transcellular water permeability is due to the presence of water (aquaporin) channels in both the apical and basolateral membrane of PT cells. Most PT transepithelial water reabsorption occurs by the transcellular pathway driven osmotically by transcellular solute reabsorption.
Water absorption from the peritubular space into the peritubular capillaries is driven by a net difference in Starling forces spanning the peritubular capillary wall favoring absorption of fluid into the peritubular capillaries. Recall the Starling forces are the difference in hydrostatic pressure and osmotic pressure inside and outside the capillary. In the glomerulus, the hydrostatic (push out) exceeds the oncotic (pull in) = filtration, but in the peritubular capillaries, this is reversed so that oncotic exceeds hydrostatic = reabsorption of water..
The paracellular movement of water from lumen to peritubular space driven by the active, Na+ transport- dependent increase in osmolarity in the lateral space is observed to entrain and “sweep” Na+ and Cl-
within the flow of fluid between cells in the direction of the peritubular capillary. This remarkable process of entrainment or “sweeping” of paracellular Na+ and Cl- across the cell layer is referred to a solvent drag,
where movement of solvent (water) drags solutes along with it between cells.
Regulation of Proximal Tubule Na+, Cl- and Water Reabsorption
- Changes in renal hemodynamics, increasing or decreasing GFR, increase or decrease the filtered load of Na+ into the PT. The PT responds by reabsorbing a constant fraction of the ___ filtered load (~67%), constituitively, independent of external neural or hormonal control. This process of “glomerulotubular (GT) balance”serves to maintain Na+ and fluid balance and defend against excessive Na+ and fluid ___ or ___.
- Angiotensin II and renal sympathetic nerve activity increase PT Na+ and water ______ when circulating volume is reduced.
Regulation of Proximal Tubule Na+, Cl- and Water Reabsorption
- Changes in renal hemodynamics, increasing or decreasing GFR, increase or decrease the filtered load of Na+ into the PT. The PT responds by reabsorbing a constant fraction of the Na+ filtered load (~67%), constituitively, independent of external neural or hormonal control. This process of “glomerulotubular (GT) balance”serves to maintain Na+ and fluid balance and defend against excessive Na+ and fluid loss or gain.
- Angiotensin II and renal sympathetic nerve activity increase PT Na+ and water reabsorption when circulating volume is reduced.
Proximal tubule has a role in Acid-base homeostasis. It constituitivly ______ most of the filtered bicarbonate and keeps its ECF concentration constant by returning it to the circulation.
PT also ____ protons generated from metabolic processes AA metabolism, production of organic acids, & bicarbonate loss in diarrhea. Secreting protons generates new HCO3- which replaces the bicarbonate lost in ____ of metabolic acids (HCO3- is becomes H2CO3 & then becomes CO2 & water so it is effectivley lost).
Proximal tubule has a role in Acid-base homeostasis. It constituitivly reabsorbs most of the filtered bicarbonate and keeps its ECF concentration constant by returning it to the circulation.
PT also secretes protons generated from metabolic processes AA metabolism, production of organic acids, & bicarbonate loss in diarrhea. Secreting protons generates new HCO3- which replaces the bicarbonate lost in buffering of metabolic acids (HCO3- is becomes H2CO3 & then becomes CO2 & water so it is effectivley lost).
Proximal Tubule HCO3 Reabsorption:
The process of proximal tubular HCO3- reabsorption is _____cellular and mostly constituitive, returning most of the filtered HCO3- to the circulation with little regulation.
Transcellular PT HCO3- reabsorption is coupled to transcellular Na+ reabsorption by a process, which involves a recycling of H+ across the luminal membrane. In the PT tubular fluid, filtered HCO3- is dehydrated by a lumenal membrane ______ to form CO2 and OH-. H+ transported ____ of the cell by a luminal membrane Na+ /H+ antiporter titrates OH- to form H2O, which moves ____ the cell (see pg. 9). CO2 diffuses across the luminal membrane into the cell and is combined with intracellular OH- by intracellular ______ to form intracellular HCO3-. The source of intracellular OH- arises from H+ transported out of the cell by a luminal membrane_____ antiporter, which leaves behind an intracellular OH- for each H+ transported out of the cell. Intracellular Na+ is actively transported out of the cell across the basolateral membrane by a Na+/K+ ATPase. Intracellular Na+ is also actively transported out of the cell across the basolateral membrane by a Na+ – HCO3- symporter, which also mediates efflux of intracellular HCO3-. The transcellular transport process mediating HCO3- reabsorption does not involve net secretion of H+.
ECF volume _____ stimulates HCO3- reabsorption (contraction alkalosis) due to an effect of Starling forces increasing PT fluid reabsorption and an effect of increased angiotensin II to increase luminal membrane Na+-H+ antiport resulting in increased Na+ and HCO3- _____.
Proximal Tubule HCO3 Reabsorption:
The process of proximal tubular HCO3- reabsorption is transcellular and mostly constituitive, returning most of the filtered HCO3- to the circulation with little regulation.
Transcellular PT HCO3- reabsorption is coupled to transcellular Na+ reabsorption by a process, which involves a recycling of H+ across the luminal membrane. In the PT tubular fluid, filtered HCO3- is dehydrated by a lumenal membrane carbonic anhydrase to form CO2 and OH-. H+ transported out of the cell by a luminal membrane Na+ /H+ antiporter titrates OH- to form H2O, which moves into the cell (see pg. 9). CO2 diffuses across the luminal membrane into the cell and is combined with intracellular OH- by intracellular carbonic anhydrase to form intracellular HCO3-. The source of intracellular OH- arises from H+ transported out of the cell by a luminal membrane Na+/H+ antiporter, which leaves behind an intracellular OH- for each H+ transported out of the cell. Intracellular Na+ is actively transported out of the cell across the basolateral membrane by a Na+/K+ ATPase. Intracellular Na+ is also actively transported out of the cell across the basolateral membrane by a Na+ – HCO3- symporter, which also mediates efflux of intracellular HCO3-. The transcellular transport process mediating HCO3- reabsorption does not involve net secretion of H+.
ECF volume contraction stimulates HCO3- reabsorption (contraction alkalosis) due to an effect of Starling forces increasing PT fluid reabsorption and an effect of increased angiotensin II to increase luminal membrane Na+-H+ antiport resulting in increased Na+ and HCO3- reabsorption.
Tubular fluid is the fluid in the tubules of the kidney. It starts as a renal ultrafiltrate in the glomerulus, changes composition through the nephron, and ends up as ____ leaving through the ureters. Hence, tubular fluid will leave as ____ if nothing is done to it.
Tubular fluid is the fluid in the tubules of the kidney. It starts as a renal ultrafiltrate in the glomerulus, changes composition through the nephron, and ends up as urine leaving through the ureters. Hence, tubular fluid will leave as urine if nothing is done to it.
