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Renal: Intro to Renal Phys (2) - (Talbot) - JCN
Talbot Part 2/2 TEST = Important
Terms in this set (55)
TRUE or FALSE: The PCT is the longest section of the neprhon, often several times longer than the DCT
2- The fluid in the PCT i similar to ?
Fluid is similar in composition to the PLASMA
The MAJOR role of the PCT is ?
TEST: List what is reabsorbed in the PCT.
- 65-80% of ions (Na, Cl, HCO3, Ca, PO4, SO4)
- 65-70% WATER
- Organic nutrients (sugars, amino acids, vitamins)
- K+ and lipophilic solutes like urea
The _______ nutrients are usually completely reabsorbed in the PCT.
TRUE or FALSE: Reabsorption of potassium is an active process in the PCT
FALSE, it is a PASSIVE process (all other ion reabsorption is active however)
TEST: List what is secreted into the PCT.
and organic IONS
TEST: How much Na is reabsorbed in the PCT compared to the rest of the nephron?
How is this done?
~67% of the total Na in the filtered load is reabsorbed in the PCT
TEST: What is the TF/P ratio, and what does it compare?
The TF/P ratio = the concentration of a given solute in the FILTRATE (or TUBULAR FLUID) at a given point along the nephron relative to the concentration of that solute in the PLASMA.
TEST: What does a TF/P ratio of 1.0 mean? What is the significance of this?
A TF/P ratio of 1.0 means the concentration of a solute in the filtrate is EQUAL to the concentration of that solute in the plasma
- This is significant → shows the solute in question is FREELY FILTERED
TEST: What does a TF/P ratio > 1.0 mean?
This means the concentration of the solute is GREATER in the FILTRATE relative to the plasma
TEST/TRUE or FALSE: A TF/P ratio > 1.0 implies the solute was actively secreted into the filtrate, resulting in a higher concentration of filtrate
FALSE, it COULD mean that.
Could also be due to water volume decreasing in the presence of solutes that DO NOT REABSORB OR SECRETE (like inulin or creatinine).
Since most of the water is being absorbed in the PCT,
as more water is being reabsorbed, there could be NO CHANGE in the solute quantity
and still yield a HIGHER TF/P ratio.
TRUE or FALSE: A TF/P (tubular fluid/plasma) ratio < 1.0 could mean that solute is being reabsorbed
could also mean that water is not being reabsorbed as fast as the solute is
, causing a lower TF concentration!
TEST: The reabsorption of most solutes from the lumen of the nephron into the ECF is directly or indirectly dependent upon the ____ electrochemical gradient maintained by the actions of the (apical/basolateral) __________ (specific pump)
Directly or indirectly
dependent upon the SODIUM electrochemical gradient
maintained by the actions of the
BASOLATERAL Na/K ATPase!!
The Na gradients, whether from the lumen to the cytoplasm or from the ECF to the cytoplasm, are both used to move other solutes (down/against) their concentration gradients.
The Na/glucose co-transporter and Na/H exchanger are examples of (apical/basolateral) Na-coupled carrier proteins
List one basolateral co-transporter used to drive Na efflux into the ECF. Which ion in this transporter is going against the gradient?
- Na against gradient (out to ECF)
- HCO3 down gradient (out to ECF)
TEST: Explain how the basolateral Na/K ATPase is used to drive the reabsorption of:
4) Urea and fat-soluble substances
5) Cl and other anions
Basolateral Na/K ATPase drives Na OUT of the cell (into the ECF).
1) This creates a concentration gradient for Na to passively DIFFUSE from the lumen into the cell
2) At the same time Na is diffusing DOWN its concentration gradient, it co-transports glucose AGAINST its gradient via SECONDARY ACTIVE TRANSPORT
3) The movement of ions out of the lumen drives WATER OUT of the lumen and into the cell
4) With a DECREASE in lumenal VOLUME, this increases the concentration of UREA and other solutes in the lumen, which then drives their TRANSCELLULAR diffusion into cell
5) Similar to urea, Cl and other anions after becoming more concentrated in the lumen due to water loss will move DOWN their concentration gradients, but PARACELLULARLY
For every solute that enters the cell across the apical membrane from the lumen, there must be what?
A basolateral transport mechanism to get it out of the cell and back into circulation!!
List a few apical membrane transporters that play a role in reabsorption of solutes in the PCT.
1) SGLT2 (Early PCT)
SGLT1 (Late PCT)
3) Na-Pi transporter
*****Which transporter accounts for ~2/3 of the Na reabsorption in the PT?
Sodium Hydrogen exchanger
List at least 3 basolateral membrane transporters that play a role in reabsorption of solutes in the PCT.
1) Na/K ATPase
2) Na-HCO3 co-transporter
3) Na/Ca exchanger
TEST: Cl reabsorption in the early PCT occurs (para/trans)-cellularly, why?
Cl reabsorption in:
- EARLY PCT = PARAcellularly
- In the
early PCT, there is more water being reabsorbed than Cl
, raising the TF/P ratio.
Since the concentration of Cl =↑↑↑ in the lumen, it will flow down its concentration gradient via PARACELLULAR routes (since it doesn't need channels or pumps)
The Cl reabsorption in the late PCT occurs (para/trans)-cellularly. Explain.
LATE PCT = TRANScellularly
- In the late PCT= ↓↓↓ concentration gradient so it needs channels and pumps that drive Cl flow TRANSCELLULARLY (the channels/pumps natural route)
What is a HYPERAMINOACIDURIA?
What causes this?
Refers to INCREASED renal excretion of AA
↑ conc of AA in plasma (METABOLIC disorder)
Genetic defects in AA transporters (
systinuria and Hartnup disease
TRUE or FALSE: The majority of potassium reabsorption occurs in the DCT, not the PCT
FALSE, ~ 80% of the filtered load of potassium is reabsorbed in the PCT!!
Proximal tubule water reabsorption is ___ ___ and about ____% of the filtered water is reabsorbed in the PCT
TEST: Essentially all K+ reabsorption is (active/passive) and (para/trans)-cellularly
PASSIVE and PARACELLULARLY
The main driving force for paracellular potassium reabsorption in the EARLY PCT is an _______ gradient, while the driving force in the LATE PCT is driven more by a ________ gradient
For potassium reabsorption:
- EARLY PCT = OSMOTIC gradient
- LATE PCT = VOLTAGE gradient (the lumen becomes positive potential in the late PCT, so naturally K+ will move away from that down its voltage gradient)
Amino acid reabsorption in the PCT is predominantly dependent on ___-coupled co-transporters on the (apical/basolateral) membrane
Predominantly dependent on SODIUM-coupled co-transporters on the APICAL membrane
(don't need to know these though)
TEST: What is the first step in reabsorbing smaller proteins and oligopeptides from the renal tubule lumen?
After this, what TWO transporters are the main players in oligopeptide reabsorption?
What is the DRIVING FORCE?
First step: Breakdown of small proteins and oligopeptides into individual amino acids and di-/tri- peptides by
brush border peptidases
Next: PEPT1 and PEPT2 coupled H+ co-transporters on the APICAL side drives uptakes of these peptides
Main driving force: H+ moving down electrochemical gradient (into the cell)
How are larger proteins such as albumin and insulin reabsorbed if the PEPT1 and PEPT2 transporters can't take them up?
What is the fate of these larger proteins?
MEGALIN and CUBILIN
Fate: Degradation after being internalized, free amino acids then returned to the ECF
TEST: The TF/P ratio (does/does not) change for osmolality all along the PCT.
What does this suggest?
Since the TF/P for osmolality
DOES NOT change, this suggests that water AND solute reabsorption are occurring SIMULTANEOUSLY
(if it didn't, then TF/P would go up or down as either solutes or water was being reabsorbed).
This keeps the number of solutes per unit volume the SAME, keeping osmolality the same.
How come the PCT has a constantly high water-permeability?
Due to the CONSTITUTIVE expression of
apical AND basolateral aquaporins!! (AQP1)
TEST: The morphology of the PCT epithelial cells also allows for high water-permeability.
Briefly explain the mechanism (hint: think about tight junctions and which end they are closed, what they form, what pumps are present, etc...)
Tight junctions between adjacent epithelial cells are closed on the APICAL side but open on the BASOLATERAL side, so it creates a LATERAL INTERCELLULAR SPACE (LIS). (
What is found on the LIS and why are they important?
Facing the LIS are many Na/K ATPases, which pump more Na into the LIS. Using AQPs for transcellular movement or paracellular through the tight junctions, water moves INTO these LISs based on OSMOTIC forces.
This increases the pressure in the LIS, and ultimately drives water towards the ECF down it's pressure gradient!
TEST: Within the PCT epithelial cells, there is an enzyme called ______ _____ that hydrates CO2 to form carbonic acid, which immediately dissociates into ___ and _____. The ______ exchanger actually secretes the ____ into the lumen while the ________ co-transporter moves the _____ back into the ECF.
Both of these transporters depend on the _______ pump to maintain a ____ gradient!!
Within the PCT epithelial cells, there is an enzyme called CARBONIC ANHYDRASE that hydrates CO2 to form carbonic acid, which immediately dissociates into H+ and HCO3-. The Na/H exchanger on the APICAL side actually SECRETES the H into the lumen while the Na/HCO3 co-transporter moves the Na back into the ECF!!
Both of these transporters depend on the Na/K ATPase pump to maintain a Na gradient!!!
PAH, or para-________ ________, is an organic anion that is (reabsorbed/secreted) into the PT in addition to being filtered.
Would you expect the TF/P ratio to be greater or less than that of Inulins? Why?
Para-aminohippurate is an organic anion that is SECRETED into the PT in addition to being filtered.
The TF/P ratio should be markedly greater than that of Inulins because inulin is only filtered and not secreted, making it less concentrated than PAH in the PCT (which is actively secreted).
This means the TF/P ratio for inulin should be lower.
TEST: Organic anions are secreted into the PCT using a series of three transporters on the basolateral side...
List what they are, and describe how they work together to drive organic anions into the PCT.
1) Na/K ATPase - Maintains a Na gradient, high outside and low inside
2) NaDC3 cotransporter - Uses the Na DOWN its gradient (into the cell) to transport dicarboxylates like DC2- into the cell via secondary active transport
3) OAT transporter - DC2- moves back out of the cell down its gradient, driving PAH (organic anion) into the cell
Organic anions are secreted into the PCT using a series of two possible transporter/channels on the apical side. What are they and what do they do?
1) PAH/Anion Antiport - Drives PAH out of the cell into the lumen in exchange for anions into the cell
2) Faciltated diffusion via PAH uniporters
TEST: Secretion of organic anions is an example of what kind of transport?
TERTIARY active transport!
(it takes 3 transporters and ion gradients to drive organic anions into the cell)
TEST: List the one basolateral transporter and one apical transporter involved in transporting organic CATIONS into the PCT.
1) OCT2 - organic cation uniport for facilitated diffusion of OCT2 into the cell (down gradient)
2) OCTN1 - Organic cation/H+ cation exchanger on apical membrane, secreting organic cations into the lumen while reabsorbing H+.
If organic cations are secreted in exchange for protons into the cell, how does the cell get those hydrogen ions back into the lumen?
Na/H exchanger, letting Na down gradient into the cell to pump H+ out to the lumen!
TRUE or FALSE: Nephrons, like enzymes, can be saturated with a high enough solute concentration so that the transport rate is working maximally
What is a clinical example of an over saturation of a solute, resulting in high levels in the urine?
The beetus (diabetes)
AGAIN: What is the equation for filtered load, or quantity of solute filtered from the plasma?
GFR x Plasma concentration of solute
AGAIN: What is the equation for the quantity of solute excreted?
Flow of urine (V) x urine concentration of solute
TEST: Assuming a constant GFR, an increase in plasma concentration of any freely filtered solute will (increase/decrease) the filtered load of that solute
Recall: Filtered load = GFR x P(solute)
- ...if you have more in the plasma, more will be filtered
For most organic nutrients, the quantity excreted from the filtered load is usually ______. Why?
ZERO, because any organic nutrients you filter SHOULD be completely reabsorbed in the PCT!!
What is the plasma threshold for a solute?
The first plasma concentration that results in solute in the urine
TRUE or FALSE: Unlike the filtered load response to increasing plasma solute concentration, the quantity excreted follows an exponential curve
it follows a LINEAR curve
(increase in filtered load is proportional to an increase in plasma solute concentration)
(Above/below) the plasma threshold, quantity reabsorbed (R) is equal to quantity filtered (+/-) quantity excreted
R = F - E
TEST: If using PAH as an estimate of renal blood flow, what conditions must you use when measuring the levels?
Must ensure that the PAH concentrations are LOW,
so that the transporters are not all used up (Tmax).
If they were, PAH wouldn't be excreted as much and would be a poor estimate for renal blood flow!
Above the plasma threshold, quantity (reabsorbed/secreted) is equal to what?
Quantity SECRETED is equal to quantity excreted - quantity filtered
S = E - F
RECAP/TEST: What is the equation for reabsorption rate in terms of GFR?
= F - E
= (GFR x plasma conc of PAH) - (Urine flow x Urine conc of PAH)
RECAP/TEST: What is the equation for secretion rate in terms of GFR?
= E - F
= (Urine flow x urine conc of PAH) - (GFR x plasma conc of PAH)
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