4 - Renal Tubular Transport Flashcards
What are processes in the kidney that determine the final composition of urine?
RPF, GFR, and reabsorption.
For many substances, what percentage of of the filtered load (from the glomerulus) is reabsorbed? Give a few examples of substances for which this is true.
Over 99%.
Glucose, bicarb, sodium, chloride.
What is the structure of renal tubules?
They are a collection of epithelial cells organized analogously to a 6-pack of cans held together with plastic rings.
Top of can = apical or luminal side of cells
Sides and bottoms of cans = basolateral or interstitial side of the cells.
Plastic rings = tight junctions
What are the basic pathways that fluid can be reabsorbed from the lumen? Is energy used?
By paracellular (across the tight junctions) or transcellular (across the cells) pathways.
This can be active (coupled to ATP) or passive diffusion.
How does water move across the renal epithelial cells?
Via osmosis, therefore it will follow solute reabsorption in the segments that are permeable to water.
Why is the mechanism for sodium handling so important?
It’s the most common cation in the ECF.
The reabsorption of other substances is dependent (directly or indirectly) on the tubular handling of sodium and potassium by the Na/K ATPase on the basolateral membranes of epithlial cells. .
What is the function of the Na/K ATPase? Why is this important?
Maintain a low intracellular Na and a high intracellular K to maintain a charge of ~70mV inside the cell.
This gradient is used in many co/counter transport systems in which other solutes are reabsorbed or secreted in mechanisms coupled to sodiums movement into the cell.
What does the proximal tubule (PT) reabsorb?
67% filtered water, Na+, and K+ (water follows Na passively-isosmotic reabsorption)
50% filtered urea
85% filtered HCO3-
~100% filtered load of glucose, amino acids, and protein.
Where is the energy for PT reabsorption obtained from?
Na/K ATPase pump.
What does the reabsorption of NaHCO3 and water generate?
A Cl- gradient which is the force for the passive reabsorption of sodium.
What is one mechanism by which sodium is reabsorbed in the PT?
1/3 occurs by the Na/H counter-transporter.
Uses electrochemical gradient for sodium reabsorption in PT cells and couples it to the secretion of H ion.
Where is bicarbonate permeable to the PT cells?
It is impermeable to the apical membrane, but the brush borders of the membrane and the cytoplasm contain carbonic anhydrase (ca).
What is the role of carbonic anhydrase?
In the tubular lumen, filtered bicarb combines with H+ ions to form carbonic acid (H2CO3); this dissociates into CO2 and H2O (catalyzed by CA).
What happens to the CO2 and H2O created by carbonic anhydrase.
CO2 diffuses into the cytoplasm to combine with water and participate in the reverse rxn to reform HCO3- and H+.
HCO3- can then move across the basolateral membrane by a transporter while H+ is secreted by the Na/H exchanger.
What are the three things that the Na/H exchanger and CA accomplish together?
Sodium reabsorption, bicarbonate reabsorption, and acid secretion.
What is a second major mechanism for sodium reabsorption in the PT?
Co-transport with glucose or amino acids. Takes advantage of the gradient favoring reabsorption of sodium.
This accounts for the reabsorption of 100% of the filtered load of glucose and aas and ~1/3 of the sodium reabsorption.
What is a third mechanism for sodium reabsorption in the PT?
An Na/H exchanger that’s coupled to an anion/Cl exchanger in which the anion is going into the lumen and the Cl- is reabsorbed.
Anions include formate, hydroxide, oxalate, or sulfate
The reabsorption of Na early in the PT leads to what?
An increase in Cl- concentration and lumen negative potential.
This provides a driving force for passive Cl- movement across the tight junction.
Na+ is reabsorbed along with Cl- through this mechanism.
How are sodium and chloride reabsorbed in the late PT?
Passive diffusion.
The reabsorption of Na+ (with water) in the early segments, leads to increased Cl and negative luminal potential, and increased urea concentration.
This leads to passive reabsorption of urea and Cl- in the late PT.
How does the proximal tubular fluid/plasma (TF/P) concentration ratio of creatine change from the beginning to the end of the PT?
Creatine is not absorbed, so the concentration increases as fluid progresses through the PT.
How does the proximal tubular fluid/plasma (TF/P) concentration ratio of Cl-, Urea, Na+, and osmolarity change throughout the PT?
Cl- and urea (like creatine) increase, which provides the driving force for their passive diffusion in the late PT.
Na+ and osmolarity are fairly constant due to isosmotic reabsorption in this segment.
How does the proximal tubular fluid/plasma (TF/P) concentration ratio of HCO3-, glucose, and amino acids change throughout the PT?
Ratio of HCO3- decreases, reflecting the reabsorption of the majority of filtered HCO3- in the PT.
Glucose and amino acids is decreases the greatest because they are almost 100% reabsorbed.
Describe the carrier mediated reabsorption of solutes in the PT? Describe this in terms of the Na/glucose co-transporter.
It is saturable.
The Na/glucose transporter will remove all of the filtered glucose up until it reaches its maximum capacity (375 mg/min). At that point, the filtered load exceeds the reabsorptive rate for glucose.
What is the difference between filtered load and reabsorption of glucose equal to?
The glucose spilled into the urine (urine glucose excretion rate).
How does filtered load relate to GFR? What does this tell us about an increase in plasma glucose concentration?
Filtered load = GFR x plasma concentration of substance
This means that filtered load will increase as plasma glucose concentration increases if GFR remains constant.
Describe the balance of hydrostatic and oncotic forces in the peritubular capillaries?
It favors reabsorption back into the blood (as opposed to net filtration like the glomerulus).
This makes sense because about 99% of filtered water and solute is reabsorbed, which must occur in the post-glomerular capillary beds.
Which osmotic pressure is higher in the peritubular capillaries?
They have a relatively low hydrostatic pressure (compared to glomerular capillaries) and a high oncotic pressure (due to the presence of proteins that were not filtered by the glomerulus).
There is also low interstitial pressure and interstitial oncotic pressure.
Net: favors reabsorption
What is an additional property of PT epithelial cells?
Secretion, the movement of solute from interstitium into the tubular lumen.
Complex process in which organic anions are secreted. These mechanisms are saturable.
Describe the secretion of PAH?
It is equal to the sum of the filtered load and secreted PAH.
When plasma PAH exceeds .1 mg/ml, the transport maximum of the organic anion secretory mechanism is exceeded.
Thus the clearance of PAH at plasma concentrations greater than 0.1 mg/ml is not an accurate measure of RPF. (must be corrected for PAH extraction)
What are the endogenous organic anions secreted in the proximal tubule?
cAMP, bile salts, hippurates, oxalate, prostaglandins, and urate.
What are the exogenous organic anions secreted in the PT?
PAH, acetazolamide, chlorothiazide, furosemide, penecillin, and salicylates.
Filtered load of PAH + secreted PAH = _________?
Excreted PAH
What are the endogenous organic cations secreted in the PT?
Creatinine, dopamine, epi, and norepi.
What are the exogenous organic cations secreted in the PT?
Atropine, isoproterenol, cimetidine, morphine, quinine, and amiloride.
What occurs in the thin descending loop of henle?
Permeable to water but limitedly permeable to solutes.
Water is reabsorbed following an osmotic gradient.
What occurs in the thin ascending loop of henle?
It is impermeable to water, but permeable to sodium and urea.
Passive reabsorption of sodium by passive diffusion.
Urea is excreted.
What occurs in the thick ascending limb of the loop of Henle?
Impermeable to water.
Differs from other segments b/c there is active transport of Na+ by the Na/K/2Cl transport mechanism, driven by the electrochem gradient for Na reabsorption.
Here ~25% of the filtered load of Na is reabsorbed.
What is another important mechanism for reabsorption in the thick ascending limb of the loop of henle?
The Na/H exchanger in the apical membrane, which allows H secretion and HCO3- reabsorption.
There is also paracellular reabsorption of divalent cations and magnesium.
What happens to the K+ reabsorbed by the Na/K/2Cl transporter in the thick ascending loop?
It diffuses back across the apical membrane.
This leads to a slightly positive luminal membrane charge that favors diffusion of cations across the tight junctions in this segment.
What occurs in the early distal tubule? What is it permeable to and what is reabsorbed?
Impermeable to water.
The primary reabsorption in this segment is by a Na/Cl co-transporter that’s sensitive to thiazide diuretic agents.
Calcium and magnesium are also reabsorbed here.
What is the function of the principal cells of the late distal tubule and cortical collecting duct?
Primary site for water reabsorption, permeability regulated by ADH.
They also reabsorb sodium and secrete potassium, which is dependent on aldosterone.
How is sodium reabsorbed in the late distal tubule and cortical collecting duct?
A sodium channel in the apical membrane, known as the epithelial sodium channel (ENaC).
Coupled to secretion of K through a separate channel.
What is a second type of cell in the collecting duct?
Where are these located specifically?
The intercalated cell: important for reabsorption of bicarb and potassium.
These are found in the collecting duct segment in the outer medulla.
How do the inner medullary collecting duct cells differ from the principal cells?
They reabsorb water in the presence of ADH.
Reabsorb Na in a process similar to principal cells, but this process is not coupled to K secretion.
In the distal portion, urea is reabsorbed, which is mediated by ADH.
