this is the second lecture in renal physiology. recall that the four basic processes of urine formation are filtration from glomerulus to bowman's capsule, reabsorption from tubules to capillaries, secretion from capillaries to tubules, and excretion into urine. this lecture covers the details of reabsorption and secretion, and introduces clearance as a way of measuring filtration of different solutes.
the mechanism of reabsorption is looked at in detail: once filtered and in the proximal convoluted tubule, molecules can be reabsorbed by crossing the tubular membrane to the endothelium of the peritubular capillaries, going from the apical side of the tubular membrane to the basolateral side. it can do this in two ways: either traversing across the luminal membrane, called transcellular transport, or going through the tight junctions that connect the tubular membrane cells, called paracellular transport. sodium is transported across the cell and involves a sodium potassium pump which actively pumps sodium from the membrane cells into the basolateral side, creating a lower concentration in the membrane cells which allows Na+ from the lumen to diffuse passively down its concentration gradient.
reabsorption of other molecules: water travels alongside electrolytes such as Na+ due to osmotic pressure, in special membrane channels called aquaporins, or through the tight junctions, often carrying small ions like Ca2+ or K+ with them (called "solvent drag"). proteins are degraded into amino acids and reabsorbed, and a fraction are reabsorbed via pinocytosis. glucose reabsorption is an example of secondary active transport, because its movement across the tubular membrane is coupled with the inflow of Na+ which, as mentioned above, is powered by the active transport of Na+ out of the tubular membrane.
transport maximum is introduced as the concentration above which a certain solute can not be reabsorbed due to saturation of the transport proteins. when the concentration of a certain solute increases beyond the transport maximum, the difference is simply excreted in the urine. diabetes mellitus is an example where the high glucose levels exceed the transport maximum and therefore is excreted in the urine.
secretion is then briefly looked at: where molecules that haven't been filtered out in the glomerulus are secreted from the peritubular capillaries into the tubular lumen to be excreted. the molecules that are secreted are mainly organic ions and drugs that are protein bound. the lower flow rate in the peritubular capillaries as compared to the glomerular capillaries allows for greater time for the dissociation of ion and protein. the ions are then transported via secondary active transport into the tubular lumen using transport proteins which couple inflow of organic anions with outflow of alpha-ketoglutarate.
next, the idea of renal clearance is introduced. it is formally defined as [the concentration per day of a given solute that is excreted] divided by [the plasma concentration of that solute], which yields a flow rate which represents the amount of plasma that is "cleared" of a certain solute by the kidneys. in other words, clearance is a measure of the kidney's ability to excrete a certain solute. different molecules have different clearances based on the amount of filtration, reabsorption, and secretion that takes place. for example, glucose is completely reabsorbed into the blood stream and thus has zero clearance. on the other hand, inulin is completely filtered and not reabsorbed at all, yielding a clearance of 125mL/min. since any inulin in the blood is completely filtered to the urine, the clearance measurement is a useful estimate of the general "glomerular filtration rate". similarly, para-aminohippuric acid is a molecule that undergoes filtration and secretion (but is not reabsorbed) and thus is used as an estimate of the total plasma flow (RPF, for "renal plasma flow") from the blood to the urine.
three pathologies related to kidney function are touched upon: acute glomerulonephritis is a blockage of the glomerulus by "Ag-Ag complexes", that is related to strep infection and is generally cleared up within 2 weeks. the chronic version of the same disease involves blockage of the glomerular pores, formation of fibrous CT, and irreversible loss of nephritic function. tubular nephritis occurs when toxins such as CCl4, mercury, or lead plug up the tubules, and generally clears up within 10-20 days.
questions
1. epithelial cells of the nephritic tubules are connected by...
2. in reabsorption, what are the two types of fluid and solute transport from the tubular lumen to the capillaries?
3. describe transcellular transport.
4. describe paracellular transport.
5. what is solvent drag and how does it relate to reabsorption?
6. describe the flow of sodium in reabsorption.
7. describe the flow of water in reabsorption.
8. describe the difference of regional permeability in the nephron and what each section reabsorbs.
9. what are some examples of organic solutes that are reabsorbed?
10. what is secondary active transport in the context of reabsorption?
11. describe the reabsorption of proteins.
12. what is the transport maximum?
13. how does the transport maximum relate to diabetes?
14. describe the process of secretion.
15. why do ions dissociate from proteins in the secretion as compared to filtration?
16. describe secondary active transport's role in secretion.
17. what is plasma clearance? how is it defined?
18. what is "virtual volume"?
19. what is inulin and why is it used as a measure of clearance?
20. what is the average clearance of inulin?
21. how is creatinine used as a measure of GFR?
22. what is the clearance of glucose?
23. what is PAH? what is RPF? how does PAH estimate RPF?
24. what is partial clearance? what is an example of a molecule that undergoes partial clearance?
25. what is acute glomerulonephritis?
26. what is chronic glomerulonephritis?
27. what is acute tubular nephritis?
answers
1. tight junctions at the apical surface, leaving lateral intercellular spaces on the basolateral side.
2. transcellular transport, paracellular transport.
3. NaCl is transported across the cells via Na/K pumps and passive transporters, water transported via aquaporins.
4. small molecules pass through tight junctions into intercellular spaces.
5. in paracellular transport, water flowing through the tight junctions can "drag" small ions Ca2+ and K+ due to osmotic forces.
6. Na+ is pumped across basolateral membrane and therefore creates concentration gradient which draws in Na+ from the lumen either by passive transport or coupled with cotransporters such as H+, HCO3-, K+, Cl-
7. water follows electrolyte movement due to osmotic pressure, through aquaporins, which are membrane proteins that are permeable to water.
8. the proximal convoluted tubule reabsorbs both Na+ and water, the ascending loop and distal convoluted tubule reabsorbs just Na+, and the collecting duct absorbs just water.
9. glucose, galactose, fructose, amino acids, acetate, water soluble vitamins.
10. the coupling of the movement of organic solutes across the luminal membrane with Na+, which is powered by a concentration gradient established by active transport of Na+ ions (see question 6).
11. most proteins are degraded into free amino acids and reabsorbed exclusively in the proximal convoluted tubule. some proteins are reabsorbed via pinocytosis.
12. transport maximum is the saturation point beyond which membrane proteins can not transport organic solutes across the luminal membrane for reabsorption.
13. in diabetes mellitus, the glucose levels are past the transport maximum levels and are excreted in the urine.
14. drugs or organic ions that are bound to proteins and thus have not been filtered through the glomerulus can be secreted from the peritubular capillaries into the tubular lumen.
15. the slower flow rate allows for greater time for the ion to dissociate
16. the movement of organic anions into the luminal membrane cell is coupled with the outward flow of alpha-ketoglutarate in "OAT 1,2,3 antiporters". the organic anions then move out into the lumen via MRP or more OAT channels.
17. for a given solute, a measure of how much is removed (excreted) from the blood plasma after filtration, reabsorption, and secretion. defined as the amount of solute excreted per concentration in plasma.
18. the theoretical portion of reabsorbed liquid that used to contain the excreted solute molecules.
19. inulin is a solute that is completely filtered but not secreted or reabsorbed, and thus it is completely excreted-- in this way it can provide a measure of glomerular filtration rate.
20. 125 mL/min
21. creatinine is almost completely filtered and minimally reabsorbed/secreted and is thus also used as an estimate for GFR. a typical value is 125 mL/min.
22. glucose is completely reabsorbed and therefore has 0 clearance.
23. PAH is para-aminohippuric acid, a molecule that is filtered and secreted, but not absorbed. thus it can provide a measure of the total plasma flow from the blood to the kidneys (filtration plus secretion), RPF.
24. partial clearance occurs when there is partial reabsorption of the molecule. for example, 180mmol/day of phosphate is filtered, and only 160mmol/day is reabsorbed, leaving 20mmol to be excreted. this creates a clearance of 14mL/min (excretion flow rate / plasma concentration = clearance), which is only part of the 125 mL total clearance estimated by inulin.
25. Ag-Ab complexes block glomerulus, often due to strep infection, clears up within 2 weeks
26. Ag-Ab complexes block glomerular pores, fibrous CT forms in glomerular capillaries, and nephrons can be irreversibly lost.
27. toxins such as CCl4, mercury, lead, block off the tubules. clears up within 10-20 days.
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