Flashcards in Katz: Proximal Tubular Transport Deck (53):
The proximal tubule primarily secretes and absorbs solutes from what capillaries?
What is the proximal tubule lined with?
Proximal tubule endothelial cells
Most solutes and water are reabsorbed from the proximal tubular lumen. What does this depend on?
INWARD Na movement into the proximal tubule endothelial cell by carrier mediated transporters DOWN the Na gradient.
OUTWARD Na movement UP it's electrochemical gradient out of the endothelial cell.
Diffusion into the peritubular capillary.
What is the mechanism for Na resorption from the proximal tubule?
BASOLATERAL Na/K ATPase pumps coupled with passive LUMINAL Na entry.
What happens to K in Na resorption in the proximal tubule?
K is RECYCLED
Brought into PT endothelial cell through the Na/K ATPase up it's gradient, then moves down it's gradient and OUT of the cell through a K channel.
What systems involving Na are present in the EARLY proximal tubule on the luminal side?
1. Na/H carrier mediated antiporter
2. Na/Glucose secondary active symporter
3. Na/AA secondary active symporter
What happens to luminal Cl in the early proximal tubule?
Luminal Cl builds UP b/c it is not yet being absorbed
What systems involving Na are present in the early proximal tubule on the basolateral side?
1. Na/K ATP as coupled with a K channel
2. Glucose/AA leave via faciliated diffusion through uniporters
3. Na/HCO3 active transport symporter
What is the transtubular potential in the early proximal tubule? Why?
There is a NEGATIVE lumen transtubular potential of -4mV d/t electrogenic transport of glucose and AA.
What is electrogenic transport?
What happens to H, Glucose and AA in the proximal tubule?
They are pumped UP their electrochemical gradients by secondary active transport (secondary to Na moving DOWN it's electrochemical gradient)
What are the 4 "masters" that control the luminal Na/H secondary active antiporter? What do they do?
Increase in intracellular Co2, Ang II, Sympathetic nerve activity
Decrease in intracellular pH
All INCREASE Na/H exchange
How much glucose does the early proximal tubule resorb via the luminal Na/Glucose secondary active transporter?
Normally 100% of the filtered glucose
How does the Na/Glucose transporter in the intestine differ from that in the proximal tubule?
The intestinal is primarily a 2 Na/ 1 Glucose secondary active symporter
If plasma glucose, which is normally 5mM (90 mg/dl), increases to 15 mM what happens? Why
Glucose begins to spill into the urine!
Some Na/glucose transporters in nephrons become SATURATED
What happens in a nephron when there is 20 mM of glucose? (norm 5mM)
All nephrons have all of their Na/glucose electrogenic luminal symporters COMPLETELY saturated. The kidney reaches its transport maximum (Tm) and glucose reabsorption is MINIMAL.
What is glucosuria? Who does it commonly affect?
When Na/Glucose transporters in the nephron are completely saturated and extra plasma glucose spills over into the urine and is EXCRETED. Water FOLLOWS the urine and the pt becomes THIRSTY.
People with Diabetes I/II
What is the MOST IMPORTANT luminal mechanism?
Cl/Formate antiporter system
What is the net effect of the Cl/Formate antiporter system?
Moves Cl (and Na) into the proximal tubule epithelial cells across the luminal membrane.
Cl moves UP its electrochemical gradient and into the cell.
Where is the density of the Cl/Formate antiporter system the greatest?
In the PROXIMAL tubule
What happens when Cl moves down it's electrochemical gradieent?
The lumen becomes POSITIVE
How is formate recycled?
Formate combines with H in the lumen to form NON-IONIZED FORMATE.
NON-IONIZED FORMATE can move through the cell membrane. Once in the membrane it ionizes into Formate and H.
H is pumped back out of the cell through a Na/H secondary active antiporter.
Formate is pumpted out of the cell through a Cl/Formate secondary active antiporter.
Besides transporters, what is another way for Cl to get out of the lumen?
Through the tight junction
Where are Na and Cl reabsorbed?
How does Cl contribute to making a positive potential difference of 4 mV created in the lumen of the proximal tubule? What does this positive potential difference do?
In the INITIAL proximal tubule there is a lot of Na/H antiport acitivity, with resorption of Na and HC03, but Cl gets left behind and the Cl concentration increases in the lumen. Tight junctions in the latter portion of the proximal tubule are permeable to this build up Cl and when Cl gushes through these tight junctions, a positive potential difference of about 4 mV is created (in the lumen) relative to the basolateral side.
Drives some Na through the tight junction
What portion of all Na, Cl and water are reabsorbed in the proximal tubule? Why is this impt?
Proximal tubule luminal fluid osmolality remains at about 300 mOsms
How does water follow solutes through the endothelial cells of the proximal tubule?
1. AQP1 (Channel mediated water movement)
2. Diffusion of water through the lipid bilayer (minor)
3. Tight junctions
Tight junctions are responsible for what percentage of solvent and solute reabsorption? Are tight junctions more or less conductive to solute and water as one progresses down the nephron?
Where is carbonic anyhydrase located? What does it do?
It is present in proximal tubule epithelial cells and also embedded in the luminal membrane with its active site facing into the lumen.
Converts H2C03 to water and C02
How is bicarbonate reabsorbed?
HC03 and H are filtered and 80% destroyed in the proximal tubule. C02 and H20 can diffuse across the membrane.
In the endothelial cell: C02 and H20 > Ca> H2C03> H and bicarb. H are secreted out of the cell in to the lumen. HC03 and Na are pumped into the blood via the proximal basolateral Na/HC03 symporter.
The proximal basolateral NBC symporter probably transports 3 HC03 for each Na. Why?
More energy is required to move Na out of the cell. The E we need to get Na out comes from HC03. HC03 moves DOWN it's EG and CG. You need at least 3 HC03 to get enough E to move a single Na.
How do water, Na, Cl, AA, glucose, Bicarp, nonpolar and polar molecules all re-enter circulation?
Through the PERITUBULAR CAPILLARIES
What is reabsorption?
Lumen to peritubular capillary, or uptake into the peritubular capillares
(Favored by local peritubular capillary starling forces
Where are peritubular capillaries always located?
On the basolateral side of all renal tubule epithelial cells
What happens when blood moves through the peritubular capillaries?
Blood from the eff arterioles (with resis> low pressure)>
goes to the peritubular capillaries>
Peritubular capillares draw fluid in>
out to renal vein
Why is reabsorption favored in the peritubular capillaries?
The net resorptive pressure favors reabsorption.
Very high osmotic pressure d/t decreased concentration of water and increased concentration of albumin in the capillary.
What percentage of Na, Cl and water are reabsorbed in the proximal tubule?
What percent of filtered bicarb is reabsorbed in the proximal tubule?
What percent of filtered AA and glucose are reabsorbed in the proximal tubule?
What is the filtered load of Na- excretion rate of Na?
The rate of Na reabsorption
25,000-200 = 24,800 mM Na/day
Solute filtered load- solute excretion rate= greater than zero. What does this mean?
Solute filtered load- solute excretion rate= Less than zero
What is polar molecular trapping?
Water is reabsorbed so luminal polar molecule concentrations b/c polar molecules are TRAPPED w/out specific transporters or channels.
What happens to the trapped polar molecules?
What is hepatic biotransoframtion?
Liver makes nonpolar toxins polar (ibuprofen)
What happens to nonpolar molecules in the lumen?
As water is reabsorbed in the lumen, luminal nonpolar molecular concentrations INCREASE and are DIFFUSIONALLY REABSORBED.
What happens to urea in the lumen?
It is only slightly polar so only gets slightly trapped
What is the "essence of renal function"?
HIGH GFR delivers a HIGH filtered load into the glomerular lumen. Polar molecules are trapped and therefore excreted rapidly. Polar ions or molecules that need to be save are reabsorbed through specialized transport systems to maintain balance. The proximal tubule serves to reabsorb the majority of the high filtered loads. Therefore, the kidney can regulate and excrete polar molecules.
What are WOA?
They are polar and equal to 6mM total.
You want to save MOST (MCAs) but not ALL WOAs.
What are MCAs that you want to save?
lactate, pyruvate and ketone bodies
What are MCAs that you don't want to save?
foreign chemicals, many drugs, and metabolites which require hepatic biotransofrmation.
What happens to MCAs?
WOA and WOBs are actively SECRETED, so MCAs are ACTIVELY REABSORBED so that they are not normally excreted unless they exceed their transport maximum.