BISC 307L 1st Edition Lecture 36 Current Lecture Overview of Kidney Function o o 4 jobs 1 Filtration leakage of fluid out of the capillaries into the glomerular tubule like plasma minus the proteins 2 Reabsorption from glomerular tubule back into the capillary most of the salt most of the water glucose amino acids general process 3 Secretion from blood into the lumen of the tubule more of a selective process concentration can change due to this Excretion what comes out of the end of the collecting duct into the renal pelvis unaltered and is excreted In loop of henle only reabsorption occurs not secretion 180 L day are filtered out of the plasma into bowmans capsule all of your plasma is filtered 60 times a day so most of it has to be recovered over 99 of the fluid that is being filtered is reabsorbed 300mOsM is the same as plasma over 70 of the fluid is reabsorbed by the end of the proximal tubule by active transport of solutes and water follows by osmosis because of the way the fluid is reabsorbed transport of mostly salt the osmolarity should stay the same and it does by the end of the loop of henle the osmolarity is 100mOsM because so much salt was reabsorbed that the osmolarity went downthis is the only part of the nephron that can produce a hypoosmotic system because sometimes you need to get rid of excess water the osmolarity at the collecting duct varies due to reabsorption of water can be as high as 1200 Renal Corpuscle o o o o o In order to understand look at the poking finger analogy The outer wall is pretty non porous but the inner wall is very porous Podocytes form filtration slits in the inner wall 3 barriers that the fluid goes through 1 pores in the endothelium 2 Basal lamina 3 Spaces in between the podocytes to enter the lumen of bowmans capsule o podocytes can change their shape and a masangial cell can also change shape and this movement can change the width of the filtration slits Filtration Fraction o o If the total plasma volume entering is 100 not all of that plasma leaks into bowmans capsule o Only about 20 of plasma volume entering gets filtered and the other 80 stays in the blood o So 20 of the volume that gets filtered over 19 gets reabsorbed Filtration Pressure o o Pressure gradient o PH 55mmHg which is very high pressure for a capillary o The total pressure is the blood pressure driving it out minus the osmotic pressure exerted by protein and minus the back pressure in bowmans capsule due to the fact that this is happening in a closed space 55 30 15 10net filtration pressure o This is what is causing the fluid to move out of the capillaries o One of the reasons that blood pressure has to be so high in the kidney capillaries is because the glomerular capillaries are all about filtration not reabsorption need it high enough so that even at the downstream end it will be pushing blood out o By the time we get to the peritubular capillaries the pressure is so low that it strongly favors reabsorption of fluid when it gets to the proximal tubule o The net filtration pressure is going to drive a glomerualr filtration rate of 180L day and this is an important measurement of kidney function this is maintained at about this level over a wide range of blood pressure o High blood pressure can cause kidney damage o Important that these structures are no overwhelmed by too much flow o Regulation of filtration rate 1 Movement of podocytes to change the resistance by which the net filtration pressure pushes out 2 Constriction of afferent and efferent arterioles Top renal blood flow is coming from the same vessels that supply the rest of the body When you have vasoconstriction of the afferent arteriole increases resistance to blood flow decreases total blood flow decrease blood pressure filtration rate down Vasoconstriction of efferent artery blood dams up upstream capillary blood pressure is higher than normal increased filtration rate 3 Extrinsic and intrinsic mechanisms 1 Extrinsic outside the kidney sympathetic nerves causes vasoconstriction and shut down of filtration rate Hemorrhage and dehydration reduces fluid loss Also circulating hormones that control this 2 Intrinsic 1 Myogenic response to stretch of smooth muscle when they are stretched by high blood pressure they stretch vasocconstriction increases resistance to flow flow rate maintained 2 Juxtaglomerular apparatus o next slide Juxtaglomerular Apparatus o o Intrinsic regulation of filtration rate o At the top of the ascending limb of the loop of henle passes in between the fork of the afferent and efferent arteriole The epithelial cells that touch the arterioles are modified and the smooth muscle cells that surround the arterioles are also modifiedcalled granular cells or JG cells The macula densa cells are sensory tissue and the JG cells are hormone tissue The macula densa is sensing the flow rate of salt through the tubule and in response they release paracrine hormones ATP prostaglandin E2 and NO and the target cells of these are the smooth muscle cells contractile vasoconstriction and granular cells secrete renin Renin is an enzyme and activates a hormone activates the angiotensin pathway Transport and Excretion General Mechanisms of Reabsorption o o Reabsorption of most stuff 1 Na reabsorbed by active transport to ECF 2 Creates electrical gradient that drives the movement of anions into the ECF paracellular route or transcellular 3 Also all of this Na and CL being moved creates an osmotic gradient which drives the reabsorbtion of water 4 K and Ca and urea are left behind which creates a concentration gradient that drives their movement back into the ECF Urea is about 50 reabsorbed Reabsorption of Na Glucose HCO3 etc o o Mechanisms for the reabsorption of Na o Every place in the proximal tubule what is driving this is Na K pumps in the basolateral membrane pumping sodium out of the basolateral membrane o They are replaced by depends on what part of the tubule you are in o In the proximal tubule a Na H antiport pumps Na into the cell and there are also Na dependent glucose and amino acid transporters that pump Na into the cell o There is also a Na inorganic phosphate PO4 H2PO4 cotransport which moves both into the cell o Brings with is phosphate so it is a phosphate reabsorbing transporter and this is inhibited strongly by PTH