Collin County Community College BIOL. 2402 Anatomy & Physiology WEEK 12 Urinary System 1 RENAL PHYSIOLOGY Glomerular Filtration Filtration process that occurs in Bowman s Capsule Blood is filtered and the filtrate ends up in the tubule system of the nephron What creates the filter system? Combination of the membrane systems of the capillaries and Bowman s capsule cells 2 1
Microscopic Anatomy of Bowman s Capsule Special cells, called Podocytes, cover the capillaries 3 Microscopic Anatomy of Bowman s Capsule Pedicels of podocytes (feet extensions) create filtration slits Podocyte in Bowman s capsule 4 2
Microscopic Anatomy of Bowman s Capsule Scanning electron microscope picture of the fingerlike filtration slits of the podocytes! Compare this with the diagram on left side and previous slide! This system provides a filtering mechanism roughly similar to a coffee filter, but much more refined! It houses 3 filtering mechanisms! 5 Microscopic Anatomy of Bowman s Capsule Filtration System in Bowman s capsule Capillary endothelial cells have many pores let everything through except blood cells and large proteins Basement membrane or Basal Lamina Is negatively charged and repels most smaller proteins Foot process of the Podocytes Form additional filtration slits that only let small molecules through 6 3
Filtration System in Bowman s capsule What are the forces involved the filter system? Similar forces that are involved in capillary fluid exchange in the tissues! Hydrostatic pressure from the blood ( = blood pressure ) Hydrostatic pressure in capsule from the filtrate Osmotic (oncotic) pressure from the blood 7 Filtration System in Bowman s capsule Filtration occurs as fluids move across the glomerulus The positive filtration pressure is the glomerular hydrostatic pressure due to blood pressure in the glomerular capillaries (GHP) Capsular hydrostatic pressure opposes (CsHP) Blood colloid osmotic pressure opposes (BCOP) Net hydrostatic pressure (NHP) = GHP CsHP Net Filtration Pressure (NFP) = GHP - CsHP - BCOP = NHP BCOP 8 4
Filtration System in Bowman s capsule Net filtration pressure is thus a modest 10 mm Hg Net filtration pressure is determined by the 3 forces 9 Bowman s capsule Net Filtration pressure (NFP) Pressure force that drives fluid out of the blood (out of the glomerulus) and into Bowman s capsule Due to the characteristics of the filter, the filtrate that passes into the tubule system of the nephron equals blood minus formed elements and minus proteins Since proteins do not leave the blood stream, but water does, the efferent arteriole will have a higher concentration of proteins and blood cells ( will be more viscous)! 10 5
Bowman s capsule Glomerular Filtration Rate (GFR) Total amount of filtrate formed per minute by the kidneys. Depends on : NFP what happens when NFP = 0? what happens to NFP when BP increases? what happens when afferent blood osmolarity increases? ( use next slide ) Total filtration area ( what happens with a unilateral nephrectomy? ) Filtration membrane permeability ( what happens when some Glomeruli get clogged up? ) 11 Bowman s capsule Blood proteins changes affect this force Blood pressure changes affect this force 12 6
Regulation of GFR Regulation of the GFR is an important homeostatic process. If GFR is too high, we would produce a high rate of filtrate and re-absorption of essential elements would not be efficient. If GFR is too low, we would not be able to secrete important waste products fast enough Regulation of the GFR occurs via 3 mechanisms Renal Auto-regulation Neural regulation Renin-Angiotensin Feedback 13 Regulation of GFR 1. Renal Auto-regulation a. Juxta Glomerular Apparatus (JGA) feedback Distal Convoluted tubule makes contact with afferent and efferent arteriole This region is called the JGA Contains 2 groups of cells that are important in kidney function Juxta glomerular cells : are part of the afferent arteriole wall and act as mechano-receptors and endocrine cells Macula Densa cells : are part of the DCT and they act as chemoreceptors/endocrine cells. 14 7
Regulation of GFR 15 16 8
Regulation of GFR 1. Renal Auto-regulation b. Myogenic Effect When blood vessels and smooth muscles are stretched they tend to contract Increased blood pressure will cause vasoconstriction in the afferent arteriole and counteract a possible increase in NFP. 17 Regulation of GFR 18 9
Regulation of GFR 2. Neural Regulation Mostly a sympathetic effect Produces powerful vasoconstriction of afferent arteriole Decreases GFR and slows production of filtrate Important for example during blood-loss ; prevents body from excreting more urine ( fluid) Changes the regional pattern of blood flow Alters GFR Also Stimulates release of renin by JGA 19 Regulation of GFR 20 10
Regulation of GFR 3. Renin-Angiotensin Feedback The following will result in a Renin release by the Juxtaglomerular cells in JGA apparatus Drop in Blood pressure (reduced stretch in afferent arteriole) Reduced release of the vasoconstrictor from the Macula Densa cells ( thus, reduced Na + flow in the DCT) Direct stimulation of JG cells by sympathetic stimuli All these stimuli release Renin, resulting in Ang II production Efferent arterioles have more Ang II receptors than Afferent arterioles ; thus this will increase the Pressure in the glomerulus (why? ) Ang. II also results in release of Aldosterone and ADH 21 ( what do they do? ) Regulation of GFR 22 11
Regulation of GFR 23 Regulation of GFR 24 12
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. 25 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. 26 13
Nephron tubule Function 27 Proximal Convoluted Tubule The function of the PCT is : Reabsorption of most organic nutrients Active reabsorption of sodium and other ions Reabsorption of water 28 14
Proximal Convoluted Tubule 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! 29 How does this occur? Proximal Convoluted Tubule Re-absorption is due to an a-symmetrical arrangement and organization of the epithelial cells lining the proximal tubule 30 15
Proximal Convoluted Tubule Longitudinal section Cross section 31 Proximal Convoluted Tubule 32 16
Proximal Convoluted Tubule 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 33 Proximal Convoluted Tubule 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 34 17
Proximal Convoluted Tubule 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 35 Proximal Convoluted Tubule 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 36 18
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. Hydrostratic 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. 37 Proximal Convoluted Tubule Lumen PCT cell Interstitial fluid Na + Na + K + PTC H 2 O -17 mm Hg Driving pressure This force helps to drive the Na + and water back into the blood stream 38 19
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 39 Proximal Convoluted Tubule Lumen Na + PCT cell Interstitial fluid Na + K + PTC Gluc Gluc -17 mm Hg Driving pressure 40 20
Proximal Convoluted Tubule 41 Proximal Convoluted Tubule 42 21
Proximal Convoluted Tubule 43 Proximal Convoluted Tubule 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. 44 22
Proximal Convoluted Tubule Renal Threshold = plasma concentration at which a substance start to spill over into the urine When this happens, urine volume increases as well. This because for each ion or molecule that is not reabsorbed, less water is redirected via osmosis (and thus ends up in the urine). 45 Proximal Convoluted Tubule Under normal conditions, renal Threshold is rarely reached. The exceptional cases are for example hyperglycemia as seen in diabetes mellitus. Renal glycosuria : Defective carriers that don t allow the PCT to reabsorb glucose. 46 23