The Proximal Tubule

Question 1

Main site of tubular secretion

Answer 1

Proximal Tubule

Question 2

Avidly secreted

Percentage reabsorbed

All of Z reabsorbed

Answer 2

AMount exrected=amount entering the kidney in the renal artery (PAH)

Amount excreted

Question 3

Transport across epithelial cells and types

Answer 3

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

Question 4

Passive trasnport type

Answer 4

Simple diffusion - slow and non-selective

Ion channels - highly selective…open-channel and gated

Facilitated diffusion…reuqires uniporters

Trasnporters exhibit stauration kinetics

Question 5

Symporter
Antiporter
ATPases

Answer 5

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

Question 6

Reabsorption of glucose in pT

Answer 6

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

Question 7

How dose Na/glucose symporter work?

Answer 7

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

Question 8

LUminal membrane Na+-glucose symporters

Answer 8

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

Question 9

Na coupled sympoters on luminal membrane

Answer 9

3 AA symports
2 phosphate symports
Na-H+ exchanges…this is an ANTIporter
Fanconi syndrome - generalized defect in proximal tubule transport

Question 10

Proximal tubule small proteins that are filtered

Answer 10

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

Question 11

PT reabsorptive capacity

Answer 11

2/3 of filtrate reabsorbed

Many solutes (glucose, AA, HCO3) COMPLETELY reabsorbed proximally

Question 12

Effect on the concentration

Answer 12

Since 2/3 of water AND solute are reabsorbed…then fluid is isosmotic and isotonic

Question 13

If isotonic (b/t tubular and IS fluid) then how does H2O move????

Answer 13

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

Question 14

Regulation of the PT fluid reabsorption

Answer 14

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)

Question 15

GT balance

Answer 15

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

Question 16

Effects of efferent arteriolar resistance

Answer 16

Increased resistance means increased Pgc so increased GFR

Also decreased Ppc

AND

Decreased RBF, increase filtration fraction, so increase Pipc

Question 17

Hemorrhage

Answer 17

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

Question 18

IN vivo micropuncture

Answer 18

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

Question 19

Secretion

Answer 19

Furosemide and butanide are loop diuretics and secreted into the proximal tubule…also PAH

Question 20

OA transports

Answer 20

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

Question 21

OA across luminal membrane

Answer 21

OAT4 antiporter pumps OA out and filtered alpha-KG in

Also MRP-2 - multidrug resistance-associated protein -2…screted OA into the lumen

Question 22

OC transport

Answer 22

Electrical gradient favors OC uptake across BM via OC transporters

LM transport mediated by OC-H+ antiporter (OCTN) and MDR 1 (p-glycoprotein)

Question 23

OATs

Answer 23

Not really selective

Can utilize this to clinical benefit

Question 24

Tm concept

Answer 24

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

Question 25

SPlay and thereshold

Answer 25

Splay - slight variance in TM between neprhons

Thresh - plasma concetration at which Tm is exceeded…normally well below

Question 26

Diabetes and gluocsuria

Answer 26

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

Question 27

Clearance

Answer 27

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

Question 28

CxCin

Answer 28

SUbstance must undergo NET reabsorption

Must undergo net secretion

Question 29

How to measure RPF

Answer 29

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

Question 30

RBF eq

Answer 30

RBF/(1-Hct)