Proximal Tubule Flashcards
What percentage of all filtered solutes and H2O are reabsorbed in the proximal tubule?
2/3
-Sum of total osmoles reabsorbed is proportional to water, Iso-osmotic
What are three different mechanisms by which to move substances?
- Diffusion
- Channels
- Transporters
What is diffusion?
Movement down a gradient. Primary method across peritubular capillary and paracellular movement.
-Only non-charged particles!!
What are channels?
They facilitate diffusion across a lipid bilayer
What are transporters?
They are generally slower facilitators than channels due to the required tight substrate binding.
What is the function of Uniporters?
Single solute movement
What is the function of Multiporters?
Move 2 or more solutes simultaneously
- Same direction (symporter)
- Opposite direction (antiporter)
What is active transport?
Moving a solute up it electrochemical gradient!
What is primary active transport?
Need to burn energy to make it happen!
What is secondary active transport?
One solute moves down its electrochemical gradient & this produces other solute energy to go against its!
In the proximal tubule what is the only transporter that requires energy??
The basolateral 3Na+-2K+ transporter!!
What happens in terms of charge in the proximal tubule cells?
More positive change pumped out than in –> this maintains negative change in cell!
What happens to K+ on the basolateral side of the proximal tubule?
K+ is recycled!
What makes up the greatest amount of “stuff” in the urine?
Na+!! (140 mM)
What makes Na+ want to come into the cell at the proximal tubule?
HUGE concentration gradient!
What is the concentration of Na+ in the proximal tubule cell?
4-10 mM
What is a unique property to remember about the peritubular capillaries?
They are fenestrated!!
What different molecules is sodium cotransported with into the proximal tubule cells?
- H+ pumped out of cell
- Glucose pumped in
- A.A. pumped in
- PO4- pumped in
What type of transport does Na+ use when pumped in along with other molecules?
Carrier mediated transport
What are the SGLT?
Sodium-Glucose Linked Transporters
Two types: SGLT1, SGLT2
90% of glucose reabsorbed in proximal tubule via SGLT2!!
How much of filtered glucose is reabsorbed in the proximal tubule?
100%!!
What is the saturation point of Na+-glucose transporters referred to as?
Tm = Transport maximum
What happens when you reach the Transport maximum (Tm) of glucose?
Once it’s reached, additional glucose will NOT be able to be reabsorbed –> glucose will remain in the urine!
What amount of glucose in the urine is abnormal?
ANY GLUCOSE
What amount of glucose in the urine is referred to as glucosuria?
15 mM of glucose
What are some potential causes of Glucosuria?
Genetic/Proximal Tubule Disorder or DM!
What carrier mediated transporters are located on the basolateral side of the proximal tubule cells?
- Na+-HCO3- symporter
- Glucose
- A.A.
In the proximal tubule glucose, A.A. and phosphorus are being pumped up their electrochemical gradient. How is this done?
Via 2ndary Active Transport!
Where is Cl- reabsorbed?
Further down he proximal tubule –> because its concentration builds up as it flows through
Where are most formate transporters located?
Late section of proximal tubule (where there is a favorable concentration gradient for Cl-)
How is Cl- transported in the proximal tubule?
2ndary active transport.
-Pumped in while formate is pumped out!
What does formate become outside the cell?
Formic acid (combined with H+)
What produces formate in the cell?
HF breaks into H+ and formate
What provides the H+ for formate outside the cell?
The Na+, H+ co transporter (Na+ in and H+ out)
What are the three means by which Cl- gets into the peritubular capillary?
- Paracellular flow
- Formate transporter –> Cl- channel
- Formate transproter –> K+, Cl- cotransproter (carrier mediated)
What is the purpose of formate in the proximal tubule cells?
- Simply used to uptake Cl-
- Formate is just recycled!!
What is important to remember about CrCl?
It is an estimate for GFR but it ALWAYS overestimates!
What should you know about MDRD?
It’s a true predictor for GFR but you need to adjust for surface area or your calculation is wrong!
(ex: 1.72 m^2 is standardized)
How much of the Bicarbonate that you filter is reclaimed in the proximal tubule?
80%
What is interesting about Bicarbonate reabsorption?
It is technically put into the urine early on and then “recreated” in the proximal tubule and put into the bloodstream
How is HCO3- transported in the urine?
HCO3- + H+ = H2CO3 = CO2 + H2O
Carbon dioxide and water
What enzyme is responsible for making bicarbonate in the proximal tubule cells?
Carbonic anhydrase converts CO2 + H2O into H2CO3 into HCO3- and H+.
What happens to the H+ and HCO3- made by carbonic anhydrase in the proximal tubule cells?
- The H+ is pumped out into urine (while Na+ is pumped in)
- 3HCO3- is cotransported into the peritubular capillary along with Na+
How is water transported/reabsorbed in the proximal tubule (3 ways)?
- H2O does minor diffusion into cell –> Aquaporins –> Peritubular capillary
- H2O enters cell through aquaporins –> enters peritubular capillary through aquaporins
- H2O is transported paracellularly
- -> water is attracted into the cell because there is a high concentration of solute within the cell
What does it mean when this equation is negative: [(Ppc + pii) - (Pi + pipc)]? Positive?
Negative - Reabsorption
Positive - Filtration
In summary, what is reabsorbed in the Proximal Tubule?
100% Glucose
80% Bicarbonate
66% (2/3) Water, Na, Cl
Why do we filter so much (180 L/day) in the kidney?
To get rid of TOXINS and take everything we need back!
What happens to substances that don’t have channels or transporters?
They MUST diffuse across the cell membrane OR be excreted.
What types of substances can diffuse across the cell membrane?
Non-polar substances (no charge!)
What happens to polar substances in the urine?
They get trapped in the urine, you excrete them!
What can the liver make if the body needs something excreted?
It can make a non-polar thing POLAR!
What are examples of Polar substances?
Waste products, drugs, toxins [cytochrome P450 makes these polar]
What happens to non-polar substances in the urine?
These can diffuse across the membrane and will not be secreted.
What are examples of non-polar substances?
Steroid hormones, O2, Cholesterol, CO2
What is NH4+ used for in the CELL and in the URINE?
To store large amounts of HYDROGEN while keeping the pH balance of urine!
What is important to know about WOA and WOB in the proximal tubule?
Most of these you don’t need!
What WOA/WOB do you NEED to SAVE in the proximal tubule?
Most physiologic WOA you need to save.
Ex: drugs, metabolites (usually arising form liver biotransformation)
What is the most important WOA/WOB you need to SAVE?
Monocarboxylic acids (MCAs) Ex: Pyruvate, Ketone bodies, Lactate
What is special about the MCA transporter?
It pumps MCA into the cell along with Na+.
It recognizes a carboxylic group - so you can hang onto those you need (WOA and WOB) but get rid of anything else.
What happens when the MCA transporter is interrupted?
Anything that interrupts this increases drug concentration/inhibits drug clearance.
How do WOA and WOB get secreted in the urine?
OAT and OBT transport WOA and WOB actively into the cell. Then carrier mediated transporters provide facilitated diffusion of the WOA and WOB into the urine.
What are the Mechanisms of Probenicid & Sulfinpyrazone?
They facilitate the excretion of Uric Acid via inhibiting OAT transporter.
How do WOA and WOB get secreted from the peritubular capillary into the cell?
OAT and OBT transport WOA and WOB actively into the plasma.
