Tubular Reabsorption and Secretion Flashcards
1
Q
reabsorption
A
- the movement of filtered solutes and water from the tubular fluid across the epithelial cell tubule into the peritubular capillaries and into the circulation
- regulated to maintain the homeostatic balance matching solute and water excretion to a variable solute and water consumption
2
Q
secretion
A
- movement of solutes from the circulation via the peri-tubular capillaries across the epithelial cell tubule into the tubular fluid
- another mechanism in addition to filtration by which solutes may be added to the tubular fluid and excreted in urine
3
Q
renal handling of solutes not excreted by the kidney
A
excreted= filtered+ secreted- reabsorbed
4
Q
general considerations
A
- concentration of filtered organic and inorganic solutes is the same in plasma and tubular ultrafiltrate. as solutes and water in the tubular fluid advance through the nephron, most water and solutes are reabsorbed and returned to circulation. urine is formed by the solutes and water not reabsorbed and by solutes secreted into tubular fluid
- most solute transport from lumen to peri-tubular space across the tubular epithelium is active and driven by energy released from ATP hydrolysis or secondary active transport
- some solute transport from lumen to peri-tubular space is passive and not driven by ATP hydrolysis
- water transport from lumen to peri-tubular space across the tubular epithelium is passive and occurs by osmosis, driven by the difference in osm in the tubular lumen and peritubular spce
- where osm high, water low, water moves down concentration gradient
5
Q
osmolarity
A
- solutes go to peritubular space and increase water concentration in tubular space and decrease it in the peri-tubular space
- water then follows
6
Q
renal epithelial transport
A
transport of solutes is:
- transcellular, occurring by uptake into and efflux from the cell in either the reabsorptive or secretory direction
- paracellular, occurring by movement of solute and water through junctions of contiguous cell in either the reabsorptive or secretory direction
7
Q
transcellular transport
A
- dependent on the coordinate function of solute specific transporters in the apical membrane facing the tubular fluid in the lumen and in the basolateral membrane facing the peritubular space and caps
- solute specific and nephron segment specific transport mechanisms mediate water and solute transport in different segments of the nephron
- Na/K pump is restricted to basolateral membrane of all renal epithelial cells in all segments of the nephrons. it maintains a steady state concentration difference- Na less in and K greater in, Na more out and K less out
- K channel, high K conductance in either luminal or basolateral membrane maintains the steady state, inside negative membrane potential difference
8
Q
transcellular transport 2
A
- lumenal and basolateral solute transport mechanisms are defined as active or passive depending on their ability to transport solutes in a direction across the cell membrane against a solute electrochemical gradient
- active transport mechanisms mediate inward or outward solute transport across the cell membrane in a direction against solute gradient and require energy
- primary active transport mechanisms capture and transduce the energy of ATP hydrolysis to the energy stored in the formation of a solute electrochemical potential gradient
9
Q
secondary active transport
A
-transduce energy stored in the electrochemical potential gradient of one solute into another solute
10
Q
co-transporters
A
- symporters
- couple driving and driven solute in same direction across membrane
- driving solute usually inwardly directed extracellular to intracellular transmembrane Na gradient
- Na down concentration gradient and brings something with it against the something’s concentration gradient
11
Q
counter transporters
A
- anti-porters
- driving and driven in opposite direction
- mediate transport in either direction across the membrane depending on which of the coupled solutes has larger gradient
12
Q
passive transport
A
- mediate solute transport across the cell membrane down a solute electrochemical potential gradient in either inward or outward direction and do not require coupling to a source of energy
- facilitated or not
- channels/pores
13
Q
paracellular transport
A
- passive and driven by a transepithelial solute electrochemical potential gradient
- depends on tightness or solute specific resistance to transport through intracellular junctions
- the ability of epithelia to maintain a trans-epithelial voltage difference or an osmotic gradient is determined by the cell to cell junctional resistance or leakiness of the epithelium to solute and water transport across the junction
- movement of water from the tubular lumen across the intercellular junctions to the peritubular space occurs by osmosis and may entrain the movement of solute by a process of solvent drag, which contributes to transtubular solute reabsorption or secretion
14
Q
functional properties of transcellular transepithelial transport
A
- coordinate function of solut specific active and passive transporters in series, in opposing membranes mediates bi directional transcellular transepithelial transfer of solutes between the tubular fluid and the peritubular space
- reabsorption and secretion is saturable and a maximum rate is achieved at defined, solute specific, plasma and/or tubular fluid solute concentrations
- transcellular reabsorption and secretion is inhibitable by drugs and circulating metabolites
15
Q
tubular reabsorption of a solute may result from
A
- active transport uptake at the luminal membrane and passive transport efflux at the basolateral membrane
- passive transport uptake at the luminal membrane and active transport efflux at the basolateral membrane
16
Q
tubular secretion can result from
A
- active transport uptake at the basolateral membrane and passive efflux at the lumenal membrane
- passive uptake at the basolateral membrane and active efflux at the lumenal membrane
17
Q
reabsorbed glucose
A
-filtered glucose- excreted glucose
18
Q
excreted glucose
A
filtered glucose-reabsorbed glucose
19
Q
reabsorbed glucose
A
Pglu x GFR- Uglu x Vurine
20
Q
renal handling of glucose
A
- filtration and reabsorption but not secretion
- amt of glucose in urine is a function of amt filtered and amt absorbed
- absorbed in the proximal tubule
21
Q
glucose reabsorption
A
- circulates between 75- 170 mg/ dl
- freely filtered from plasm at glomerulus
- at normal levels all is reabsorbed at proximal tubule
- clearance of glucose is zero at normal but begins to increase around levels of 200 mg/dl-threshold plasma concentration
22
Q
Tm
A
- tubular reabsorptive maximum
- maximum solute reabsorptive rate or capacity for tubular solute reabsorption
- as plasma solute concentration approaches Tm, the transport mechanisms get saturated and solute begins to appear in urine
23
Q
membrane transport mechanisms for glucose
A
lumenal membrane:
- Na-glu cotransporters mediate concentrative accumulation of glucose inside the cell driven by inwardly directed Na current
- ratio is 1:2:1, resulting in net positive charge transfer with each glucose transported; electrogenic and sensitive to membrane potential as an additional DF to increase glucose concentration
basolateral membrane:
passive efflux of intracellular glucose mediated by facilitated diffusion (uniporter)
24
Q
excreted PO4
A
-filtered - reabsorbed
25
Q
reabsorbed PO4
A
filtered- excreted
PO4 x GFR- Upo4 x V urine
26
Q
filtered load of phosphate
A
- 250 mMole/day, more than 10x the extracellular pool
- reabsorption in proximal tubule, 90% of filtered load returned to circulation
- reabsorption increases with increasing filtered load of phosphate and approaches a tubular maximum of phosphate reabsorption where the process of transcellular transport becomes saturated and rate of reabsorption is maximal and constant
27
Q
renal handling of PO4
A
- linear relationships for filtered and excreted
- Tm is maximum amt reabsorbed
- at normal levels, almost all reabsorbed
28
Q
transcellular phosphate mechanisms
A
Lumenal membrane:
- Na/PO4 co transporters
- 2:3:1- net positive transfer with each PO4 transported
- sensitive to membrane potential as an additional DF
- titration of dibasic to monobasic by increasing tubular fluid acidity inhibits PO4 transport by decreasing the concentration of dibasic PO4 and the transport of dibasic PO4
basolateral membrane:
-passive efflux
29
Q
renal handling of amino acids
A
-circulating levels of aa arise from GI absorption, protein catabolism and de novo synthesis
-filtered at glomerulus and completely reabsorbed across proximal tubule by AA specific, transceullular transport mechanisms mediating
-active uptake at the luminal membrane (Na-symport) and passive efflux at basolateral membrane (facilitated diffusion)
-saturable above Tm, then above are excreted in urine
-
30
Q
secretion 2
A
- blood borne solutes enter tubular fluid by transcellular secretion from peritubular space to the tubular lumen across various segments of the nephron
- foreign to the body- toxins/drugs
- metabolized by kidney for excretion by kidney
- metabolized by the liver (glucuronidation, sulfation) for excretion by kidney
- regulated in blood
31
Q
renal handling of PAH
A
- secreted =excreted- filtered
- excreted= filtered+ secreted
- secreted = Upah x V urine - Ppah x GFR
- secreted into tubule
- amt of PAH excreted is a function of amy filtered and amt secreted
32
Q
renal handling of PAH 2
A
- exogenous, monovalent organic ion
- freely filtered
- at low circulating levels, so effectively secreted by the proximal tubule that its clearance form the renal circulation is complete and no PAH exits the kidney in the renal vein
- Tm is tubular secretion maximum, defines max rate
- as plasma concentration of PAH increase, Tm for PAH achieved, transport mechs become saturated and PAH appears in renal vein
- PAH secretion becomes a smaller fraction of the PAH in the urine, the PAH filtration becomes larger fraction of amt in urine
33
Q
PAH transcellular transport mechanisms
A
basolateral membrane:
- Na/ dicarboxylate co transporter mediates accumulation of ketoglutarate inside the cell
- and organic anion antiporter mediates concentrative exchange of intracellular ketoglutarate for extracellular PAH
- 1:1, but divalent for monovalent, so net negative charge out of cell, which is another DF to get PAH in
lumenal membrane:
- efflux of PAH by facilitated diffusion
- or actively by anion gradient driven antiport
34
Q
excretion of PAH measures renal plasma flow
A
- rate of plasma solute entry into the kidney in the renal artery is equal to the rate of solute exit from the kidney into the urine and renal veins
- rate PAH entering kidney=rate PAH leaving
- RPF x Ppah= RPFvein x Pvein PAH + U pah x V urine
when all is excreted, RPF x Ppah= Upah x V, RPF= Upah x V / Ppah**
rate of PAH entering = RPF x P pah
35
Q
renal handling of salicylate
A
-circulates in plasma and is filtered in its neutral weak acid for and conjugate base form
36
Q
secretion of salicylate
A
- active basolateral and passive luminal transport of the conjugate base across proximal tubule
- PAH and salicylate are substrates of the same active basolateral and passive luminal transporters
37
Q
reabsorption of salicylate
A
- occurs primarily by the passive process of non-ionic diffusion across the distal nephron
- decreases with increased tubular fluid pH and flow rates
- increases with decreasing tubular fluid pH and flow rates
38
Q
pH and salicylate
A
-when pH is high, there is secretion, at low pH there is reabsorption
