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module 11 - renal system.docx

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Western University
Physiology 2130
Ingrid L.Stefanovic

Module 11 – Renal System, Water & Electrolyte Balance Contents Introduction  Renal system include: o Kidneys o Ureters o Bladder o Urethra  The principal function of the kidneys is the regulation of water balance, electrolyte levels, pH of the blood & LT regulation of arterial pressure Function of the Kidneys  The basic function of the kidneys is to remove nonessential substances from the plasma, including waste metabolites, excess water, and electroytes and to recover any essential substance like glucose  In doing so, the kidneys play a major role in regulating the water levels, the chemical conc of the body fluid compartments, and pH (acidity) of the blood  The kidneys do not produce water or electrolytes but only conserve them by reducing the amount removed from the body  The eliminate of waste or foreign substances is an important function of the kidneys o Removal of drugs, food additives, and vitamins that are excreted in the urine  The kidneys also act as an endocrine gland, producing hormones/components of hormonal systems such as erythropoietin, renin, vit D, and stanniocalcin Anatomy of the Kidneys  Kidneys = size of a fist  Consist of an outer renal cortex, middle renal medulla, and inner calyces that drain into a central renal pelvis  The renal pelvis then drains into the ureter  Located within the renal pyramids are the functional units of the kidneys (the nephrons) o Each nephron drains through a collecting duct into a calyx Anatomy – Blood Supply of the Kidneys  Blood flows to the kidneys through the: o Renal artery  interlobar arteries  arcuate arteries  interlobular arties (supplies the nephron) o The blood supply to the nephron drains into the interlobular vein  arcuate vein  interlobar vein  renal vein Anatomy – The Nephron  The nephron = functional unit of the kidneys  There are over 1 million nephrons in each kidney whose function is to filter the blood, reabsorb essential substances and excrete nonessential molecules and waste  Each nephron is composed of a highly coiled hollow tube surrounded by a complex blood supply  Glomerular capsule (Bowman’s capsule) surrounds a very small, highly permeable capillary bed called the glomerulus o These structures are often collectively referred to as the renal corpuscle  The tubular portion of the nephron consists of the following structures in order: o Proximal convoluted tubule (highly coiled portion of the nephron) o Descending and ascending limb of the loop of Henle o Distal convoluted tubule o Collecting duct Anatomy – Blood Supply of the Nephron  Very complex  Blood from the renal artery eventually reaches the interlobular artery that drains into the afferent arteriole o Afferent arteriole gives rise to the glomerulus (where filtration takes place) o The blood from the glomerulus enters the efferent arteriole  peritubular capillaries (dense network of capillaries surrounding the tubes of the nephron)  drains into the interlobular vein and eventually back to the renal vein The Renal Corpuscle  Renal corpuscle = glomerular (Bowman’s) capsule + glomerulus  This is the site where the blood is filtered (glomerular filtration)  Filtrate - fluid that is filtered from the blood that enters the glomerular capsule (or capsular space)  Glomerular filtration is facilitated by a highly permeable capillary endothelium this is surrounded by podocytes  The larger diameter afferent arteriole and smaller diameter efferent arteriole also enhance glomerular filtration Processes along the Nephron  Each section of the nephron has different functions o These functions can be broken into:  Filtration  Reabsorption  Secretion Processes along the Nephron – Important Terms  Filtration – movement of fluid (solution) through the glomerular capillary due to hydrostatic pressures (pressure gradient)  Filtrate – solution created by filtration (filtered at renal corpuscle) o Filtrate is generally composed of water plus all the dissolved solutes in the blood (except for large proteins that are too big to be filtered)  Reabsorption – movement of a substance from the lumen of the nephron back into the blood  Secretion – movement of substance from the blood  lumen of the nephron  Excretion – removal of a substance from the body (kidneys)  Excretion = filtration + secretion – reabsorption Glomerular Filtration  Bulk flow of fluid from the blood  glomerular capsule  This fluid (filtrate) contains the same substances as plasma with the exception of large proteins and RBCs  Glomerular filtration is affected by the extremely permeable capillaries, which make up the glomerulus, and Starling Forces  The glomerular capillary has many fenestrations  Special epithelial cells (podocytes) surround the capillaries o The podocytes have large filtration slits that are formed btwn pedicles  These structural features increase filtration at the glomerulus Glomerular Filtration – Starling Forces  Starling Forces cause the bulk movement of fluid across capillaries due to a combo of hydrostatic and colloid osmotic forces  Blood hydrostatic pressure = 60 mmHg o Almost 2x that in a regular capillary, causing filtration of fluid into the glomerular capsule o This pressure is principally due to the difference in diameter btwn the afferent (large) and efferent (small) arterioles  Colloid Osmotic Pressure due to plasma proteins = -32 mmHg o Causing reabsorption of fluid into the plasma  Capsular Hydrostatic Pressure = -18mmHg (reabsorption of fluid)  There is no colloid osmotic force in the globular capsule since very few proteins are filtered o Therefore, the resulting net filtration pressure = 10 mmHg out of the glomerulus into the capsular space Glomerular Filtration Rate (GFR) and Filtered Load  The kidneys filter a tremendous amount of fluid each day – 180L/day  Glomerular Filtration Rate (GFR) – volume of fluid that is filtered by the glomerulus during a certain time period  Bc the kidneys filter many other substances, it is important to be able to calculate the filtered load - the amount of these substances filtered by the kidneys per day o Filtered load = GFR x plasma conc of the substance  Examples of GFR and Filtered Load o Both GFR and filtered load can tell a physician a lot about how the kidneys are functioning o Ie. glucose is almost completely filtered by the glomerulus, but it is all reabsorbed by the nephron in healthy individuals o Therefore, no glucose should be excreted in the urine o On the other hand, you’d expect to find some Na+ in the urine since it is both filtered and excreted  Its important to calculate also its urine concentration and the amount of solute excreted o These values also tell the physician important info concerning the health and functioning of the kidneys  Urine concentration = amount of the solute that is excreted per unit of urine (g/L)  Amount of solute excreted = actual amount (in grams) of solute that is excreted in the urine o Amount excreted = urine conc x amount of water excreted per day (1.8L/day)  Amount reabsorbed = amount of filtered substance that is taken back up (reabsorbed) by the kidneys o Amount reabsorbed = filtered load – amount excreted  Fraction excreted = (amount excreted/filtered load) x 100%  Example: o Glomerular filtration rate = 180L/day o Na+ plasma conc = 5g/L o Amount of Na+ reabsorbed = 626g/day o Amount of water excreted = 1.8L  Calculate the concentration of Na+ in the urine (in g/L) o How much Na+ is being excreted? 1. Amt. excreted = amt. filtered + amt. secreted – amt. reabsorbed a. Na+ is not secreted in this example therefore take it out 2. Amt. excreted = filtered load – amt. reabsorbed a. Were given the amount of Na+ reabsorbed but not the filtered load 3. Filtered load = GFR x plasma conc a. = 180 x 5 b. = 900 g – this is what is being filtered at the glomerulus 4. Amt excreted = 900 – 626 a. = 274 g – this is the amount of Na+ excreted in the urine. However we want the concentration! 5. Amt of Na+ excreted = urine concentration x amt of water excreted a. Urine conc of Na+ = amt of Na+ excreted/amt of water excreted i. 274 g/1.8L ii. = 152.2 g of Na+/L of urine = urine concentration of Na+ Tubular Transport Mechanism – Introduction  From the proximal convoluted tubule to the collecting duct  Throughout these sections of the nephron, reabsorption (blue) and secretion (pink) occur to different substances in a regulated & non- regulated manner  Reabsorption and secretion involve a number of transport mechanisms including: o Active transport o Secondary active transport o Facilitated diffusion o Simple diffusion o Osmosis (in the case of water) Tubular Transport Mechanisms – Reabsorption  Over 99% of the substances filtered in the glomerulus are reabsorbed back into the circulation at different sites along the nephron  When molecules are reabsorbed from the filtrate back into the circulation, there are two transport routes that can be taken: paracellular and/or transcellular transport  The tubular cells are joined tg by tight junctions o Generally these tight functions don’t allow substances to cross btwn the cells. However, along the nephron, these tight junctions vary and can be quite leaky o As a result, some substances can diffuse btwn the tubular cells by paracellular transport  Other substances are transported across the tubular cell membrane from the lumen into the cell, then into the interstitial fluid and into the blood o This form of reabsorption = transcellular (transepithelial) transport  In many cases, transcellular transport can be regulated (increased/decreased) by hormones o However, most cases of transcellular transport are non-regulated and occur without any hormonal control  Paracellular transport is generally non-regulated, occurring without any hormone control Tubular Transport Mechanism – Reabsorption – The Na+/K+ Pump  Many of the transport mechanisms along the nephron rely upon the Na+/K+ pump that we have seen many times  Recall that this pump is an active transport mechanism bc it requires ATP in order to move 3 Na+ out of the cell and 2 K+ into the cell o As a result, it helps establish a concentration gradient for both ions across the cell membrane  A high concentration of Na+ outside the cell and low inside  A high concentration of K+ inside the cell and low outside Tubular Transport Mechanisms – Reabsorption – Secondary Active Transport  In secondary active transport, the Na+ conc gradient that is established by the Na+/K+ pump is used to power other transporters o As Na+ moves into the cell down its concentration gradient, other substances will either move in with the Na+ or will move out in exchange with the incoming Na+ o Secondary active transporters include the Na+/glucose co-transporter and the Na+/H+ exchanger  Na+/glucose co-transporter is located on the luminal side of tubule cells o With this transporter, as each Na+ diffuses into the cell, a single glucose molecule is carried in along with it  Na+/H+ exchanger is also located on the luminal side of the cells o Moves one H+ out of the cell for every Na+ that diffuses in Tubular Transport Mechanism – Secretion  Secretion – kidneys remove unwanted substances from blood  lumen of nephron  Secretion is generally a hormonally regulated process but in some cases it can occur without any hormone control (non-regulated)  Most substances that are secreted are eventually excreted in the urine  Secreted substances include H+ and K+ o This process does rely on the presence of the Na+/K+ pump Tubular Transport Mechanisms  Na+ reabsorption: o Takes place in the proximal tubule, ascending limb of the loop of Henle and early distal tubule – mostly by non-regulated mechanisms o However, Na+ reabsorption in the proximal tubule can also be regulated by the hormone angiotensin II and by the hormone aldosterone in the late distal tubule and collecting duct  In a healthy individual, all the glucose that is filtered at the glomerulus is reabsorbed in the proximal tubule  Amino acids, building blocks of proteins, are also reabsorbed in the proximal tube  Water reabsorption takes place in the proximal tubule and descending limb of the loop of Henle through non-regulated mechanisms o No water is reabsorbed in the ascending limb of the loop of Henle o Water reabsorption is regulated by antidiuretic hormone (ADH) in the late distal tubule and collecting duct  K+ reabsorption takes place in the proximal tubule and the ascending limb of the loop of Henle o Secretion of K+ occurs in small amounts in the ascending limb of the loop of Henle o Larger amounts of this ion are secreted in the late section of the distal tubule and collecting duct under the influence of the hormone aldosterone  H+ secretion occurs in the proximal tubule and the ascending limb of the loop of Henle – it can be both regulated and non-regulated o H+ are also secreted in the late distal tubule and collecting duct Proximal Convoluted Tubule – Reabsorption of Na+, Glucose, and Amino Acids  Proximal convoluted tubule reabsorbs ~66% of the total filtrate o Na+/K+ pump is one of the most important transport mechanisms of the nephron  Due to the Na+ concentration gradient established by the pump, Na+ can be reabsorbed into the tubule cells by simple diffusion, Na+/glucose co- transporter or the Na+/H+ exchanger o Na+/H+ exchanger can be regulated by the hormone angiotensin II  Amino acids are also reabsorbed along this section of the nephron by a Na+/amino acid co-transporter similar to Na+/glucose co-transporter  In a healthy individual, the Na+/glucose co-transporter reabsorbs all of the glucose in the filtrate, however this is not the case in people with diabetes mellitus Proximal Convoluted Tubule – Diabetes Mellitus  Diabetes mellitus is a disease that affects the pancreas’ ability to produce the hormone insulin o Insulin = essential for cells to take up and store glucose after a meal o Therefore, without insulin, glucose concentrations build up in the blood o Large quantities of glucose are filtered by the glomerulus, and as a result the Na+/glucose co-transporters cannot reabsorb all of it  Consequently, some is excreted in the urine  This is one of the important symptoms of diabetes mellitus – glucose in the urine o Since this co-active transport system is a form of secondary active transport, it can be saturated  Ie. single postal worker trying to sort all of the mail coming down a fast conveyor belt, a lot of glucose will get by the pumps Proximal Convoluted Tubule – Reabsorption of Water  Now that Na+, glucose and amino acids have been reabsorbed, the filtrate will have a lower solute concentration (and higher water concentration) compared to the cell and interstitial fluid  With this osmotic gradient and the presence of special water channels (aquaporins), water will move down its concentration gradient by osmosis causing it to be reabsorbed  Water will be reabsorbed by both paracellular transport btwn the cells and by transcellular transport across the cells  *Water reabsorption takes place only AFTER solutes have been reabsorbed – particularly Na+* Proximal Convoluted Tubule – Potassium and Chloride  65% of all the filtered K+ and Cl- are reabsorbed in the proximal tubule  All of this reabsorption is through 2 types of paracellular transport – both of which are not regulated o Recall: the tubule cells are joined tg by tight junctions and that these junctions can be leaky – particularly in the proximal tubule  Cl- are also reabsorbed in the proximal tubule by transcellular transport Proximal Convoluted Tubule – Potassium and Chloride Reabsorption  Reabsorption of K+ and Cl- occurs by two paracellular mechanisms: o Solvent drag  Involves the reabsorption of K+ with the movement of water  Water is reabsorbed by osmosis btwn the tubule cells and this water as it moves btwn the cells also carries with it some of the dissolved substances in the filtrate – incl K+  Solvent drag = movement of a solute (K+) in a solvent (water) o Simple diffusion  Reabsorption of K+ down its concentration gradient  Water is reabsorbed by osmosis by both paracellular and transcellular mechanisms  As water is absorbed through the tubule cells, K+ remain in the filtrate  As more water is reabsorbed alone, the filtrate becomes more and more concentrated with K+  As a result, the K+ concentration gradient increases to the point where K+ can move into the interstitial space btwn the tubule cells (paracellular route) via simple diffusion Reabsorption of Filtrate Back into the Circulation  The cells lining the proximal tubule reabsorb a great deal of material (Na+, glucose, water from the lumen of the nephron)  How does all this material return to the circulation? o This material must first leave the cells and enter the interstitial space o Na+ will leave the tubule cells by Na+/K+ pump o Glucose + AA are transported across the basal membrane of the cells by specific facilitated diffusion transporters o Remember K+ are reabsorbed by paracellular transport so they are already in the interstitial fluid o Once in the interstitial fluid, all these substances are reabsorbed into the circulation by Starling Forces  Reabsorption of water and all dissolved molecules from the interstitial space back into the peritubular capillaries occurs due to Starling Forces o The pressures for these Starling Forces around the tubule cells are much different than those around a typical capillary o In the kidney, the capillary hydrostatic force (Pc) = 13 mmHg o Interstitial hydrostatic force (Pif) = 6 mmHg o Osmotic force due to proteins in the plasma (pieP) = 32 mmHg o Interstitial osmotic force (pieIF) = 15 mmHg o As a result, the net filtration pressure moving the fluid, which is equal to (Pc – Pif) – (pieP – pieIF) is calculated to be -10 mmHg or 10 mmHg moving back into the capillary  Note: the very large osmotic pressure caused by the plasma proteins  This pressure is large bc during glomerular filtration, almost all substances were filtered except large proteins Proximal Convoluted Tubule – Concentration of Filtrate  After reabsorbing Na+, glucose, AA, K+ and water, the concentration of the filtrate leaving the proximal tubule will not have changed significantly from what it was at the beginning of the tubule
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