Proximal Tubule Flashcards
1
Q
general considerations
A
- the kidney maintains ECF solute and fluid volume homeostasis by filtration and reabsorption. amt reabsorbed depends on prevailing balance between amt of solute and water consumed and amt exiting the eCF by respiration, sweating, defecation, and urination
- each segment of the nephron may be considered for its constitutive and regulatory function with regard to the renal handling of solutes and water. constitutive function occurs with little regulation and mediates a lesser renal response to changes in solute or fluid balance. regulatory function of different segments of the nephron mediates the renal response to changes in balance
- proximal tubule is the nephron segment mediating reabsorption of approx 67% of filtered water and NaCk. most of this is constitutive and may increase only when severely volume depleted
- occurs isosmotically, without a change in NaCl concentration in the 33% of the tubular fluid remaining in the PT. its leaky, permitting rapid equilibration of solutes and water across epithelium
2
Q
general considerations 2
A
- PT is the nephron segment mediating reabsorption of most of the organic solutes filtered by plasma (glucose, aa, mono/dicarboxylates, vitamins) as well as bicarbonate and some inorganic solutes
- most organic solute reabsorption is constitutive and saturabel.
- PT also mediates secretion of organic anions (drugs, metabolites) into the lumen to be excreted
- also organic cations
3
Q
changes in solute composition from early to late
A
- TF/P
- rises for inulin because it isn’t reabsorbed, so concentration increases
- 1 for Na because reabsorption of Na and water is the same in PT, constant Na concentration
- Na concentration in tubule doesn’t change because Na and water leave, not just Na
- increase in TF/P for Cl-referential reabsorption of HCO3 rather than Cl in early PT
- decrease in TF/P for HCO3, aa, glucose indicates reabsorption from tubular fluid, which adds to reabsorption of water
4
Q
change in voltage along PT
A
- neg 3 to pos 3
- originally more cations exiting and more anions present, which then switches
- first 25%, more cations out, second 75%, more anions out
5
Q
proximal tubule Na reabsorption
A
- Na diffuses in due to gradient
- then pumped out
- diffuses back into lumen paracellularly due to voltage gradient from Na/K pump (in early PT, 33% leaks)
- in late PT, voltage difference reverses and drives paracellular Na from lumen into peri-tubular space
- passive efflux of Na in serves as symport for other solutes
- out is by Na/K and Na/HCO3 symport
6
Q
Cl reabsorption
A
- paracellular in late and early
- transcellular in late PT- uptake at apical and efflux at basolateral
- paracellular early is driven by neg voltage difference
- due to preferential reabsorption of HCO3 in early PT, lumenal Cl concentration is higher than plasma concentration in late PT, and an outward Cl gradient exists (lumen to blood), which drives paracellular efflux of lumenal Cl (into blood)
- paracellular efflux then creates a lumen positive diffusion potential, which drives paracellular efflux of Na in late PT
- transcellular Cl mediates most transport in late PT, active uptake across apical membrane from solute antiport driven by outwardly directed anion concentration gradient (base out, Cl in, then acid re-conjugtes, diffuses, and H drives Na uptake and base drives Cl uptake)
- passive efflux across basolateral mediated by Cl channel and by K/Cl symporter
7
Q
PT water reabsorption
A
- most of the filtrate is returned to the circulation at the PT, reabsorption occurs without a change in osmolarity. PT reabsorption of water is passive and occurs between and across cells. DF is osmotic gradient resulting from active solute reabsorption
- high water permeability permits a large lumen to peritubule movement of water in response to a small osmotic gradient. high transcellular water permeability is due to the presence of water channels in apical and basolateral membrane of PT cells. most PT transepithelial water reabsorption occurs by the transcellular pathway driven osmotically by transcellular solute reabsorption
- from peri tubular space to caps is driven by a net difference in Starling forces favoring absorption into the caps
- paracellular movement off water from lumen to peri tubular space also causes solvent drag
PT reabsorbs constant fraction of Na filtered load- 67%, so changes in renal hemodynamics dont affect it- glomerulotubular balance
8
Q
angiotensin II and renal SNS
A
-increase PT Na and water reabsorption when circulating volume is reduced
9
Q
Role of proximal tubule in acid base homeostasis
A
- reabsorb and return most filtered HCO3 to circulation maintaining ECF HCO3 concentration at 24 mM. PT reabsorption is mostly constitutive
- secrete H generated from:
1. metabolism of aa
2. production of organic acids like lactic, or acetoacetate or b-hydroxybutyrate
3. intestinal HCO3 loss, may decrease ECF pH
*process of secreting H generates new HCO3, which replaces HCO3 lost in buffering organic and inorganic acid
10
Q
PT HCO3 reabsorption
A
- transcellular, mostly constitutive, returns most to circulation
- coupled to transcellular Na reabsorption and recycles H across luminal membrane
- HCO3 is dissociated, CO2, Na, across (antiporter with H, which makes water), water across, then reassociates and exported
- water dissociation inside gives OH to re make HCO3 with CO2, and the other H goes back out (either alone or antiported to Na) to be recycled into water
- HCO3 pumped out basolateral with Na symporter, dissociates on other side
- doesn’t involve net secretion of H
- saturable, threshold of 40 mM
- ECF volume contraction stimulates HCO3 reabsorption 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 increase Na and HCO3 reabsorption
11
Q
proximal tubule secretion of H
A
- renal excretion of H as titratable acid and NH4
- renal excretion of H as titratable acid results from titration of dibasic phosphoric acid to monobasic. pK of phosphoric acid (6.8) makes it a good buffer of H at the pH of PT fluid (7.4-6.8)
- renal excretion of H as NH4 results from titration of NH3 to 3. PT, thick ascending loop and collecting duct participate in excretion of H as NH4. in PT, origin of NH3 is intracellular glutamine metabolism secondary to active glutamine uptake across luminal and basolateral membrane
12
Q
proximal tubule excretion of H as titratable acid
A
-not all H’s used to move HCO3 in
some protons also titrate filtered phosphate to monobasic, which begins process of making new HCO3 because there is a deficit of intracellular protons and extra OHs
-new HCO3 is made and returned to circulation to replace ones lost in buffering
-replenishes the continuous depletion of HCO3 in the ECF as acid is generated from metabolism and buffered by HCO3`
13
Q
titratable acid excretion
A
- protons generated by metabolism are ultimately excreted in the urine by titration of filtered phosphate and generation of new bicarbonate
- proton excretion as titratable acid (PO4-)
14
Q
proximal tubule excretion of H as NH4
A
- protons secreted by PT are excreted as ammonium
- arises from intracellular metabolism of glutamine
- generates NH3 and OH
- NH3 pK is 9.2- titrated to NH4
- luminal membrane Na/H antiporter transports NH4 as well as H in exchange for N across the membrane and mediates efflux of NH4
- smaller amount of NH3 freely diffuses across luminal membrane into tubular fluid and trapped by titration
- protons from Na/H exchanger or H-ATPase
- for each NH3 titrated to NH4, a proton is trapped and excreted in urine and new HCO3 is made in the proximal tubule for return to circulation
15
Q
respiratory acidosis
A
- hypoventilation
- increase in ECF PCO2
- increase in proximal tubule H secretion as NH4 and an increase in HCO3 synthesis, which increases ECF HCO3 in proportion with CO2
- maintains ratio of HCO3 to CO2 close to 20 and maintains ECF pH close to 7.4
