Collin College BIOL. 2402 Anatomy & Physiology Urinary System 1 Summary of Glomerular Filtrate Glomerular filtration produces fluid similar to plasma without proteins GFR ~ 125 ml per min If nothing else would happen, we would create urine at this rate. The result would be extreme water loss, and loss of all electrolytes and nutrients. 2 1
Nephron tubule Function The function of the nephron tubules is to reclaim as much possible of the essential elements and redirect it back into the blood stream. This will involve : Reabsorption important organic nutrients Active and passive reabsorption of sodium and other ions Reabsorption of water At the same time, unwanted chemical are added to the filtrate via secretion from the blood stream into the tubules. 3 Nephron tubule Function 4 2
The function of the PCT is : Reabsorption of most organic nutrients Active reabsorption of sodium and other ions Reabsorption of water 5 Of the 125 ml of filtrate that enters the PCT per minute, only 40 ml/min passes on to the loop of Henle In addition, 60% of Na +, 50% of K + and Cl -, and 100% of all organic nutrients and bicarbonate are reabsorbed! 6 3
How does this occur? Re-absorption is due to an a-symmetrical arrangement and organization of the epithelial cells lining the proximal tubule 7 Longitudinal section Cross section 8 4
9 The plasma membrane of each epithelial cell that does not face the lumen is called the baso-lateral membrane and resembles membranes of normal cells that area of these cell contains many Na-K pumps. also contains many channels that promote facilitated diffusion for glucose and amino acids 10 5
That part of the epithelial cell facing the lumen of the proximal tubule has a plasma membrane forming many microvilli (brush border) the apical part of each epithelium cell ( thus the part which forms the brush border) does not contain Na-K pumps but does contain Na + leakage channels and Cl - leakage channels 11 The Na-K pumps in the baso-lateral membrane function as usual: pumps Na out and K in, keeping Na low inside the cell by using ATP. This creates a high gradient for Na from lumen of the PCT into the cell of the PCT. Sodium will then diffuse into the cell via specific Na-leakage channels located in the brushborder ( and sodium will leave again via the basolateral membrane via Na-K pumps) To maintain electrical neutrality, each Na moved in will promote the movement of a negative charge ( Chloride ion) via leakage channels for that ion 12 6
Lumen PCT cell Interstitial fluid Na + Na + K + Active transport of sodium out of the cell at the basolateral membrane thus promotes the re-absorption of sodium at the brush border area. The re-absorption of Sodium and Chloride promotes the uptake of water in order to maintain osmotic equilibrium 13 Forces at the Peritubular Capillaries As blood flows from the glomerulus to the peritubular capillaries, it has a higher osmotic concentration. There is also a substantial drop in pressure. The pressure forces are now revered. Hydrostatic pressure of the blood ~ (15 mm Hg ; an outward force) Blood osmotic pressure ~ (30 mm Hg ; inward force) Interstitial pressure ~ ( 2 mm Hg ; inward) Net Force = 15-2 - 30 = -17 mm Hg into the peritubular capillaries. 14 7
Lumen PCT cell Interstitial fluid Na + Na + PTC H 2 O K + -17 mm Hg Driving pressure This force helps to drive the Na + and water back into the blood stream 15 Glucose re-absorption in PCT Brush border membranes also contain channels that couple the movement of sodium to that of glucose (secondary active transport- cotransport) Similar transport systems are present for amino acids to that of certain amino Thus movement of sodium down its concentration gradient drags glucose in, even when glucose is higher in the cell Results in a build up of glucose in the cell which then leaves the cell via facilitated diffusion channels in the basolateral membrane to be reabsorbed by the peritubular capillaries 16 8
Lumen Na + Gluc PCT cell Na + Gluc Interstitial fluid K + PTC -17 mm Hg Driving pressure 17 18 9
19 20 10
Normally all amino acids and glucose are reabsorbed by the proximal tubule. However, when the transporters are 'over-loaded because their maximal transport capacity is surpassed, these components start to spill over into the urine Maximal transport rate of the transporters is called the Tm value. 21 Renal Threshold = plasma concentration at which a substance start to spill over into the urine For humans, normal renal threshold for glucose is about 180 mg/100 ml plasma. Above that, glucose will spill over into the urine Renal Glycosuria When this happens, urine volume increases as well. 22 11
Under normal conditions, renal Threshold is rarely reached. The exceptional cases are for example hyperglycemia as seen in diabetes mellitus. Familial Renal glycosuria : Deficiency in the renal Na/ glucose co-transportes, called SGLT-2 carriers. Characterized by persistent urinary glucose excretion even when blood glucose levels are normal. 23 Amino acids are removed from the filtrate in the PCT via a similar Na + -co-transport on the apical side and a directed towards the peritubular capillaries via specific facilitated transporter on basolateral side Di - and Tri-peptides are taken up via Hydrogen co-transporters. Inside the cell, the peptides are broken down to individual amino acids and then shuttled out via the basolateral side Renal threshold for amino acids is 65 mg/dl. After a protein-rich meal, amino acids commonly appear in urine (aminoaciduria) 24 12