The Proximal Tubule Flashcards
Main site of tubular secretion
Proximal Tubule
Avidly secreted
Percentage reabsorbed
All of Z reabsorbed
AMount exrected=amount entering the kidney in the renal artery (PAH)
Amount excreted
Transport across epithelial cells and types
Renal epithelial cells have a luminal and a basolateral membrane
Transcellular - through the cell across 2 membranes
Paracellular - between cells (across tight junctions by simple diffusion)
The (primary) transcellular route - requires transport proteins on both membranes
Passive trasnport type
Simple diffusion - slow and non-selective
Ion channels - highly selective…open-channel and gated
Facilitated diffusion…reuqires uniporters
Trasnporters exhibit stauration kinetics
Symporter
Antiporter
ATPases
Two or more by same protein
Two solutes moving in opposite directions across membrane
For both sym and antiporter - one solute will be moving WITH favorable EC gradient
ATPases - pumping AGAINST the EC gradient
Reabsorption of glucose in pT
Absolute dep on Na+-K+-ATPase located on basolateral membrane
Downhill flux of Na across luminal membrane into the cell facilitates uphill movement of glucose into the cell via the Na+-glucose symporter
How dose Na/glucose symporter work?
Na binds to carrier
Na binding creates high affinity for glucose
Glucose binding changes conformation so binding sites face the ICF
Na released into cytosol where Na is low…release changes the glucose binding to low affinity and therefore glucose is released
ATPase trnapsorts Na across the basolateral membrnae
Glucose uniporter (GLUT2) transports glucose out of cell across the basolateral membrane
LUminal membrane Na+-glucose symporters
SGLT-2 - high capacity-low affinity…on the early part of the PCT…Often inhibited by diabetic medications
SGLT-1…low capacity-high affinty (late PCT)
This is because there is tons of glucose at beginning and decreases towards the end
Na coupled sympoters on luminal membrane
3 AA symports
2 phosphate symports
Na-H+ exchanges…this is an ANTIporter
Fanconi syndrome - generalized defect in proximal tubule transport
Proximal tubule small proteins that are filtered
Rabsorbed via receptor-mediated endocytosis
Filtered proteins bind to megalin and cubulin in luminal clathrin coated pits
Endocytosed proteins degraded to AA and released basolaterally
Similar mech for uptake of 25-OH Vit D prior to mitochondrial conversion to 1,25-OH Vit D by 1-alpha hydroxylase
PT reabsorptive capacity
2/3 of filtrate reabsorbed
Many solutes (glucose, AA, HCO3) COMPLETELY reabsorbed proximally
Effect on the concentration
Since 2/3 of water AND solute are reabsorbed…then fluid is isosmotic and isotonic
If isotonic (b/t tubular and IS fluid) then how does H2O move????
SOlute transport creates a small transepithelial osmotic grdient (tubular fluid slightly LOWER than the EC fluid)…basically the solute resbsorbed first
Water moves from the lumen to the interstitium down this osmotic gradient
High fludi flux with small osmotic gradient due to aquaporins (water channels) in both luminal and basolateral membrane
Regulation of the PT fluid reabsorption
Complete reapsorption is 2 step process…take from lumen to interstitium…then from intersittium to peritubular capillaries
Phase 2 movement depends on STARLING forces…low Pc (downstream of affarent.efferent resistance points) and high Pipc (filtration creates high PC plasma protein concentration)
GT balance
Proximal tubule reabsorbs a constant percentage of the fiiltered load…relatively constant delivery of fluid to the distal nephron
If GFR increases, this helps tone down the amount sent to loop of Henle
Effects of efferent arteriolar resistance
Increased resistance means increased Pgc so increased GFR
Also decreased Ppc
AND
Decreased RBF, increase filtration fraction, so increase Pipc
Hemorrhage
Decreased BP and high sympathetic nerve activity (constricting AA) - decreased GFR
Angiotensin 2 — EA constriction — Increased GFR
Ensures sufficiently high GFR to filter and therefore excrete waste product efficiencyyl
GT balance minimizes loss of filtered fluid due to elevated GFR
IN vivo micropuncture
Pipette A samples tubular fluid at last accessible point of proximal tubule…difference in composition of this fluid and plasam respresents transport along proximal tubule
No transport in the last 30% or so…reason being that tubule begins to descend into the deeper cortex and is inaccessible
Dufference between Proximal and distal gives you effects of late proximal tubule (pars recta) and segments of the loop of henle
CANOOT access collecting tubule function or trnasport in juxtamedullary neprhons
Secretion
Furosemide and butanide are loop diuretics and secreted into the proximal tubule…also PAH
OA transports
Taken up across basolaterla membrnae in exchange for alpha-keotglutarate via OAT 1 and 3
Effluxed alpha-KG taken back into the cell via Na+-dicarboxylate symporter (NaDC)
Down-hill flux of Na into the cell via the NaDC due to the Na-K-ATPase
OA across luminal membrane
OAT4 antiporter pumps OA out and filtered alpha-KG in
Also MRP-2 - multidrug resistance-associated protein -2…screted OA into the lumen
OC transport
Electrical gradient favors OC uptake across BM via OC transporters
LM transport mediated by OC-H+ antiporter (OCTN) and MDR 1 (p-glycoprotein)
OATs
Not really selective
Can utilize this to clinical benefit
Tm concept
Since reabsorption is channel or carrier-mediated, there must be a maximal transport capacity when all carriers stuarated - tubular transport max
Consider renal handling of glucose…amount filtered=GFR*Pgl
Amount excreted=V*Ugl
AMount reabsorbed=amount filtered-amount excreted
SPlay and thereshold
Splay - slight variance in TM between neprhons
Thresh - plasma concetration at which Tm is exceeded…normally well below
Diabetes and gluocsuria
NOT a compensatory response by the kidneys to lower the Pgl
Since plasam glucose so high, filtered load of gluocse is way above the Tm
Clearance
Measure of GFR
Must use substance not reabsorbed or secreted by neprhon or metabolized or produced by the kidney
Eamples - Inulin or creatinine (endogenous metabolite of creatine)
GFR = (V*Uin)/Pin
Basically volume over time
CxCin
SUbstance must undergo NET reabsorption
Must undergo net secretion
How to measure RPF
RPFaPx = RPFvPx + Ux*V
Basially measuring the amount in and out via both renal vein and urine
At low concetrations, all PAH delivered to kideny is either filtered or secreted…therefore PAH in renal vein is 0…SO
RBF = (Upah*V)/Ppah
you eliminate the amoutn out part
RBF eq
RBF/(1-Hct)
