this lecture is the third in the series on the kidney and talks about one of its main functions, osmoregulation, which is the kidney's control over the concentration of solute and volume of body fluid by controlling the permeability of different sections of the nephron. the first section introduces some basic concepts regarding osmolarity in general- osmolarity is defined as moles of solute per kg of solvent and is functionally equivalent to osmolality (moles/L). the tonicity of a fluid refers to the osmolality and thus the amount of dissolved solute. if a cell is in a hypertonic solution, that means the solution it is in has more solute dissolved in it, and thus it has the tendency to shrink because of the water will flow into solution. if a cell is in a hypotonic solution, the cell now has a higher concentration of dissolved solute particles, causing water to flow inward, causing the cell to swell. thus in order to avoid such potentially damaging forces to the cell, osmolarity of body fluids need to be tightly regulated.
we then talk about the mechanism of osmoregulation in the kidney, beginning by looking at the hypertonic medullary interstitium. this is the space outside of the nephritic tubules that has a high concentration of solutes such as NaCl and urea, which are suspended in hyaluronic acid gel and albumin. the high concentration of solute (thus "hypertonic") in the interstitium provides an osmotic force for water to be reabsorbed from the nephron back into the body fluids. urea is looked at first: urea is in general a byproduct of protein metabolism- breaking down proteins forms nitrogen, which is converted to the non toxic, water soluble ammonia. ammonia is reduced in the muscles and peripheral tissues to glutamine, and in the liver glutamine is converted to urea. in the kidney, urea is filtered into the nephron and 50% is reabsorbed in the proximal tubule, while 10% is transported out into the lower medullary interstitium, contributing to its hypertonicity, and 40% is excreted in the urine.
NaCl is reabsorbed into the interstitium in the thin and thick ascending loops of henle. NaCl is first concentrated in the descending loop of henle-- this is due to osmotic pressure from high lactate concentrations (which is produced by the vasa recta because of its use of anaerobic respiration) in the surrounding interstitium, pulling water out from the descending loop. the descending loop is permeable to water but not to sodium, which allows the NaCl to become progressively more concentrated. the concentrated NaCl then flows passively out of the thin ascending loop down its concentration gradient into the interstitium, and it is actively pumped out in the thick ascending loop.
thus, the high concentrations of solute cause the interstitium to have a higher solute concentration than the nephritic tubules and reabsorption is facilitated. the vasa recta's role is then touched upon-- specifically, why it does not dilute the hypertonicity of the interstitium, since it is permeable to both water and sodium. as the blood flows down the vasa recta into the deeper medulla, solute is absorbed from the hypertonic interstitium. however, because of the vasa recta's parallel/hairpin shape, on the way up, solute diffuses back into the interstitium, so that the net effect is simply that solute is removed from the lower medullary interstitium and moved to the upper medullary interstitium.
the role of ADH is looked at in some detail. ADH "anti diuretic hormone" is a hormone that increases the permeability of the collecting duct by upregulating the transcription of aquaporin proteins, which then migrate to the cell surface and allow water to pass through the tubule (recall transcellular transport from lecture 1 on the kidney). it is produced in the PV and SO nuclei in the hypothalamus, transported into the pituitary via axonal transport, and released into the bloodstream. ADH can be produced in response to high sodium levels in the body, causing more water to be reabsorbed and the sodium levels to be diluted. ADH production can also be decreased in response to an excess of water- reducing the permeability of the collecting ducts and causing more water to be excreted in the urine. finally, the baroreceptors that sense mean arterial pressure of the blood inhibit ADH production if blood pressure is too high, reducing blood fluid volume and thus lowering blood pressure.
questions
1. what are the two parameters that regulate extracellular fluid size and composition?
2. excretion of water volume is regulated by indicators of...
3. excretion of sodium is regulated by signals derived from...
4. what are the units of osmolality?
5. a cell in a hypotonic solution...
6. a cell in a hypertonic solution...
7. what are the two factors that influence water reabsorption in the collecting ducts of the kidney?
8. what makes the medullay interstitium hypertonic?
9. urea enters the interstitium from...
10. NaCl enters the interstitium from...
11. what makes up the gel that suspends the solutes in the interstitium?
12. where does urea enter the tubules in short nephrons?
13. how does urea get recirculated back into the tubules?
14. 50% of urea is reabsorbed...
15. the bulk of the deep interstitium's hypertonicity is from...
16. which part of the nephron is impermeable to water?
17. what happens to urea in the collecting ducts?
18. urea is transported into the interstitium via...
19. urea is a byproduct of...
20. amino acid nitrogen forms...
21. describe the formation of urea from ammonium.
22. how does NaCl accumulate in the interstitium of the outer medulla?
23. how does NaCl accumulate in the interstitium of the inner medulla?
24. describe lactate's role in NaCl accumulation in the interstitium.
25. descending loop is permeable to...
26. ascending loop is permeable to...
27. describe the absorbption of solutes in the vasa recta.
28. how does the vasa recta preserve the hypertonicity of the interstitium?
29. where is ADH released from?
30. what does ADH do in the nephron?
31. describe the effect of water reabsorption on the blood.
32. how does ADH increase water permeability of the collecting ducts?
33. what is the minor calyx's role in water reabsorption?
34. action of minor calyces first seen in...
35. how often do rat pelvo-calyceal walls contract?
36. what happens during pulsatile contractions in the rat pevlo-calyceal walls?
37. what happens during relaxation?
38. what are the major locations within the hypothalamus that relate to release of ADH?
39. describe the production of ADH.
40. what do osmoreceptor cells in the hypothalamus do?
41. describe the effects of increased and decreased plasma Na+ concentration on the release of ADH.
42. how are baroreceptors in the heart related to ADH?
43. what are some other factors that stimulate/inhibit ADH release?
44. what is central / pituitary DI?
45. what is nephrogenic DI?
46. effects of lowered ADH include...
47. what is SIADH?
48. what does the hypothalamic thirst center respond to?
49. excess water consumption...
50. polydipsia is...
answers
1. fluid volume and solute concentration (sodium and water)
2. sodium concentration
3. hydrostatic pressure / body fluid volume
4. mol solute / kg solvent
5. swells
6. shrinks
7. hypertonic medullary interstitium provides osmotic pressure for water to travel outward. ADH controls permeability of tubular epithelium.
8. urea and NaCl
9. collecting duct
10. thin and thick portions of the ascending loop.
11. hyaluronic acid and albumin.
12. from the descending vasa recta
13. either through the ascending vasa recta or directly back into the tubules from the interstitium.
14. in the proximal convoluted tubule
15. the 10% of the urea that is reabsorbed in the collecting ducts.
16. the thick ascending loop of henle, the collecting tubules, and the upper collecting ducts.
17. it gets concentrated via reabsorbption of water.
18. ADH dependent transporters in the deepest part of the collecting ducts.
19. protein digestion
20. nitrogen, which is then converted into ammonia, which can be dissolved and excreted.
21. muscles and peripheral tissues convert ammonia into glutamine from reduction of alpha keto glutarate. glutamine is converted in the liver back into urea.
22. active transport via sodium/potassium pumps.
23. passive transport from thin ascending loop.
24. lactate is produced from the anaerobic respiration that occurs in the vasa recta ("due to low blood perfusion"), and accumulates in the interstitium. this pulls water out of the descending loop of henle, thereby concentrating the NaCl. the NaCl is then passively diffused out from the thing ascending loop or actively transported in the thick ascending loop.
25. water
26. sodium
27. absorbs solutes in the inner medulla but releases them in the outer medulla.
28. although blood absorbs solutes from and loses water to the interstitium as it travels down the descending vasa recta, the flows are reversed in the ascending vasa recta-- a consequence of the hairpin structure.
29. hypothalamus into the bloodstream.
30. increases permeability of collecting duct to water, allowing for reabsorption
31. increases blood volume and decreases osmolarity.
32. by increasing the transcription and translation of the genes that code for aquaporins, which are then translocated from the cytoplasm to the cell membrane.
33. it puts physical pressure on the collecting ducts and interstitium, facilitating water reabsorption.
34. the rat unipapillate model.
35. 15-40 times a minutes
36. during contraction, water is squeezed out of the collecting ducts into the interstitium (held by hyaluronic acid), concentrating the urine.
37. during relaxation, decreased interstitial pressure draws water from the interstitium into the vasa recta.
38. supraoptic and paraventricular hypothalamic nuclei.
39. ADH is synthesized in the SO and PV nuclei in the hypothalamus, transported via axons into the posterior pituitary, and then released into circulation.
40. stimulate release of ADH from PV and SO nuclei.
41. increased Na+ (from food intake) stimulates release of ADH, which causes reabsorption of water, diluting the Na+. decreased Na+ (from water intake) decreases ADH release; water is excreted in urine.
42. baroreceptors are the stretch receptors that monitor blood flow. if blood pressure gets too high, they can inhibit ADH production, which will cause net fluid loss and decrease blood pressure.
43. nausea, nicotine, morphine stimulate ADH release. alcohol inhibits ADH release.
44. reduced pituitary secretion of ADH due to genetics, head trauma, brain tumor, or infections.
45. nephrogenic DI is tubular resistance to ADH due to errors in ADH receptors or aquaporins.
46. lowered permeability of collecting ducts reduces water reabsorption, reduces urea reabsorption (and therefore lowers hypertonicity of interstitium), leads to copious urine excretion.
47. unregulated release of ADH causes excess reabsorption of water, concentrated urine, and decreased Na+ blood concentration.
48. ECF osmolarity, drop in blood volume, angiotensin II, dryness of mouth/throat
49. suppresses ADH release
50. water intoxication- causes headache, loss of apptite, lethargy, nausea. decrease in plasma sodium concentration.
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