Last time we took an introduction about the function of the urinary system and the structure or the anatomy of the kidney .also we said that the functional unit of the kidney called (nephrone ), Nephrone :it is the functional unit of the kidney which perform the job of the kidney (the formation of urine generally ). The functions of the kidney : 1. Filtration of the blood 2. Reabsorption process ,occurs in the nephrons 3. Secretion (active secretion ) of some harmful substances ,finally formation and excretion of urine . The main parts of the nephron: 1. Renal corpuscle 2. Tubular system First ,the renal corpuscle composed of : a) Glomerulus :which is a capillaries( the finstrated type of capillaries ) b) Glomerular (Bowman’s )capsule :which envelope the glomerulus Secoundly, the tubular system: It is continuous with bowman’s capsule ( continuation of the inner space of the capsule ) . The component of the tubular system : a) The proximal convoluted tubule (PCT) b) Loop of Henle, which has descending and ascending (limb)parts . c) Distal convoluted tubule (DCT) d) The collecting duct ,all collecting ducts gather and pour in to the papillary ducts these papillary ducts ,which drain to the minor calyces ( the apex ) of the renal pyramidal . The two major type of nephrone : (according to their localization ) Cortical nephrone : 85% of the all nephrons are from this type ,the majority of nephrone are cortical nephrons , most of parts of this type are located in the cortex of the kidney Juxtamedullary nephron : 15% of the total nephrons ,they called juxtamedullary nephrone , since most of their parts are located in the border between the cortex and the medulla in a region called juxtamedulla The criteria The location Length of loops Ability to /nephron type distinguish the loop parts Cortical nephrons Major parts are located in the cortex Juxtamedullary Most of their parts are nephron located on the border between the cortex and the medulla They are shorter longer loops ,and they extended deeply in the medulla Not clear to be distinguished (the tick from the thin ) Can be distinguished very clearly (such as the thin from the thick 1 (juxtamedulla ) ,approximate to the papilla descending or ascending ) The importance of juxtamedullary nephron : It has the capability to concentrate urine more efficient than cortical nepheron ,because the interstitial osmolarity concentration increased as we move down in the medulla so by osmosis the reabsorption occur more efficiently >>so the concentrating of the tubular fluid will also occur more efficiently the blood supply of the nephron how does the blood came to nephron to be filtrated and what happen after that ? *back to the slide that shows you the blood supply of the nephron the blood supply came by afferent arteriole very small division from the renal artery(this artery undergo a lots of division until it reach the afferent arteriole) the afferent arteriole inters the glomerulus ,where the capillaries emerged from the afferent arteriole , then all of the capillaries get to gather (converge) and back in the form of efferent arteriole ,not in the form of venioles as we learned in the previous semester the pathway of the blood in the nephron is :afferent arteriole >>capillaries (the glomerulus ) >>efferent arteriole (the blood which exit the glomerulus and inter this blood vessel )>>after that another division emerged from it called (peritubular capillaries ,another group of capillaries different from the glomerulus )these capillaries circumvents around the tubular system now what is the benefit from these capillaries and this circumvents ??? in order to make re absorption for the substances that need to be reabsorbed from the tubular fluid and back to the blood On the Nephron Blood Supply slid (the simple diagram ) No.2 represent :reabsorbtion So the processes of reabsorption : 1. first filtrated fluid (No.1) on the picture in the slid 2. (No.2)there is a lot of the fluid and the substances or solutes existent ,need to go back to the capillaries to return to the circulation . 3. (No.3 )is the secretion (the active secretion )to get rid of the toxic substances found in the blood more efficiently than the filtration although some of these substances have been filtrated in the first step ,but still there is some we need to get rid of them by the active secretion of these substances . 4. At the end, the fluid (or the net tubular fluid ) become urine and the urinary excretion happen . Peritubular capillaries in the juxtamedullary nephron they called them (Vasa Recta) due to their special shape & function . Note: in the slid of cortical nephron blood supply , it is not required from us to know the details ( )اسماء التفرعات غير مطلوبةbut just take a look on how these embranchments of veins and arteries make a net , how the afferent enter and the efferent exit . 2 notice that there is a venioles come out from the peritubular capillaries ,these venioles will converge in to a vein then back to the renal vein finally to the inferior vena cave which drain the blood to the heart in this stage the blood is filtrated . juxtamedullary nephron in comparison with the cortical nephron, it has a special shape their, loop is too long so this what makes the artery side of the capillaries parallel to the venous side of the capillaries and the same one matrix around them so they called them Vasa Recta they serve the same function “the ability to concentrate the urine more efficiently ,when the body need to make concentration ,because not always the body wants to do this only in some cases for example when we want to keep the water in the body . the structure of renal corpuscle : o there are strange cells adhere to the capillaries in the glomerulus it is not from the capillaries wall they are not endothelial cells .but these cells have extensions and large nucleus these cells are parts of the inner surface(visceral surface ) of bowman's capsule ,which adhere very closely to the capillaries walls of the glomerulus these cells called podocytes since they have extensions called (pedicels )and between these pedicels there are spaces called (filtration slits ) o after the blood inters the glomerulus via the afferent arteriole this blood undergo filtration across the endothelial cells this filtrate passes through the spaces between these cells then through the pedicles finally inters bowman's capsule o the space between the visceral and the outré surface of the bowman’s capsule called inter capsular space o the first segment will face the blood it is the (proximal convoluted tubule )then continues to the whole tubular system . o 20% of the blood that reached the kidney undergo filtration only and the remain 80% back via the afferent arteriole to the branches on the peritubular capillaries then return to the venous side so this is the cycle of blood filtration . o now we will talk about part actually it is a part of the tubular system but located very closely to the afferent arteriole wall ,and it is part of the distal convoluted tubule or the last segment of the thick ascending limb. o it is adheres to the afferent arteriole wall the benefit of this is : to get feedback mechanism depending on the nature of the fluid which reaches this stage . o why it gives this message to the afferent arteriole ? because this afferent is the valve ,which control the amount of blood which inters the glomerulus , according to this it will determine the amount of blood will be filtrated . o if the filtration exceed the normal rate ,the distal ascending convoluted tubule will give a message to the afferent arteriole that the filtration rate is too much so reduce the blood flow o this is the aim of this system(apparatus system ) which composed of : 3 cells from the last segment of the thick ascending (limb)tubule these cells called (macula densa ) which are very close to the afferent arteriole wall ,also these cells are specialized cells although they are part of the distal convoluted tubule but it has different appearance with a dark color .these cells ,according to the delivery of (NaCl) existing in the tubular fluid ,they send a message to the afferent arteriole either to increase or decrease the blood flow that will reach the glomerulus . certain cells that found in the wall of the afferent arteriole called (juxtaglomerular cells ). so this is the apparatus system which responsible of the feedback mechanism "the renal auto regulation "to the kidney itself by which the kidney or the nephron control it is own function. o there is another type of cells located between the afferent and the efferent arteriole called ( mesangial cells or contractile cells );these cells can contract or relax in order to control surface area of the glomerulus ,because if the surface area changed the filtration will be affected also .in which as the surface area increase the filtration will increase . the histology of the filtration membrane : what makes the glomerula very efficient in filtration in which it can form the urine daily and filtrate the blood 60 times daily back to the slide o the yellow layer it is the endothelial cells layer (consists of cells but they are not closely packed together they have spaces between them ,pores it is fenestrated )these pores make this layer have high ability of filtration, so the substances will pass through the pores between these cells according to their size the substances which are equal in size to the pores or smaller they will pass .the size of pores is exactly the size of the albumen molecule .so we expect that the albumen can cross these pores theoretically but the next layer will face the albumen it is the basal lamina or the basement membrane o you know that the endothelial cells lies on the basement membrane ,which is composed of fibers protein ,proteoglaicans, collagen ,fibrin ,microfilament ,etc. all of these fibers are carrying negative charge ,so any protein will pass this layer will face a repulsion from the basal lamina so we conclude that proteins even the albumen are not favored to be filtrated. o The third barrier after the basal lamina is the :slits ,the pedicles and the podocytes all of these forming the third barrier .the podocytes of the inner surface of the capsule as we said that they extend their pedicles very close to the capillaries ,in which it can control the filtration o The conclusion is the molecule size should be small enough to pass through these pores and slits 4 o so these are the barriers that will face the substances during filtration . two special conditions determine whether this substance will pass or not : 1. the size of molecule (the molecular size )it should equal or be less than the pores size 2. the charge :if the substances are neutral or positively charged they can easily pass in compared of those holding a negative charge. That’s explain why the albumen protein (negatively charged ) can’t get out (been filtrated ) even “theoretically” if it can fit the pores size . The cells also will not be filtrated because they are large The substances that success to pass all these barriers we called them the filtrate or (the tubular fluid) This filtrate will undergo another process which is the reabsorption in loop of henle to the valuable substances and most of the water that have been filtrated The conclusion :the histology or the composition of the nephron parts matches their functions ,which means the type of cells which make each part fit it’s function . What are the forces that govern the filtration and makes the blood filtrated ? There are some forces that favor filtration to happen ,which occur in the glomerulus to allow the fluid to get out of the glomerulus to reach bowman’s capsule to form the filtrate . So the filtration occur by physical forces These physical forces start with the hydrostatic pressure which comes from the blood in the afferent arteriole to the glomerulus ,this pressure comes originally from the pumping of the heart ,when it reach the afferent arteriole it will exert pressure equal = 55mmHg and it will try to push the blood to the outside (to the capsular space )of the capillaries through the . 1. The glomerular blood hydrostatic pressure (GBHP):it is directed toward the capsule (with the direction of filtration )so we will give it a positive charge . Force toward the direction of filtration (+ve) Force against the direction of filtration (-ve) 2. Capsular hydrostatic pressure (CHP):Force in the capsule from the fluid since it has a volume so it will exert a hydrostatic pressure on the walls ,but the direction of the pressure is against the filtration (-ve ) and equal 15mmHg it is not big but we have to consider it 3. The third force it is the blood colloidal osmotic pressure (BCOP): it happens due to the protein which remain in the capillaries ,so this pressure will try to return the fluid back to the capillaries so this pressure (glomerular colloid oncotic pressure )works against the filtration (-ve )and equal 30mmHg 4. There is no colloidal pressure in the capsular space :because the albumen remain in the capillaries and should not present in the filtrate .so this pressure is negligible nearly equal( 0 mmHg ). The net filtration pressure(NFP) : 55-30-15= 10 mmHg and it is positive which means with the direction of filtration (from the 5 capillaries in the glomerulus to bowman’s capsule )this is the normal situation to get normal glomerular filtration . Any increase or decrease in the net filtration pressure it will affect directly and largely the filtration Now, suppose that the hydrostatic glomerular pressure drop 10mmHg what will happen ?? the net filtration pressure will become 0mmHg ,so no filtration will occur ,actually this will happen if any one of these pressures changed the net filtration pressure will become 0 or( –ve )>>so no filtration >>the kidney’s job gone The net filtration pressure (10mmHg ) they are very important to get normal filtration rate ,if this drop to 5mmHg >>the glomerular filtration rate will drop to the half Important terms : 1. Renal blood flow (RBF): which comes from the afferent arteriole ,the filtration will happen to 20% of the blood flow which reach the glomerulus and the 80% which remains continue the cycle of blood .this 20% we will called it the filtration fraction . 2. Glomerular filtration rate (GFR): means how many (mLs )of the plasma that has been filtrated in each minute ,so it is the volume of plasma has been filtrated from the nephron in the 2 kidneys in each minute. The GFR =180 L daily ,here we just talking about the filtration we didn’t mentioned the reabsorption yet ,so this 180 L equal 60 time our normal volume of plasma!!! ,this means the same plasma filtrated 60 times daily to get this 180l/day . in one minute 125ml/minute from the 2 kidneys How much plasma or (blood )must reach the kidneys? (in order to get this 125ml/minute of the filtrated plasma and this must be equivalent to the 20% of the plasma or blood has been reached to the kidney ) by the equation : 20% x total plasma (flow rate )= 125mL /minute The total plasma need to reached the kidney = 625 mL/minute t These are needed to get normal GFR as we know that 55% of our blood is plasma so the total renal blood flow =1140 mL (in the book this number =1200mL/min they are close to each other ,remember this is an average ) blood must reach the kidneys to get 625mL plasma >>from which we will have(20%of the total blood reached the kidneys ) or 125mL/minute as a filtrate All of these strait ward equations just to determine the optimum amount of blood must arrives (which is 20% of blood volume ) to the kidneys to get the perfect hydrostatic pressure and normal filtration . If this blood flow decreases >>the rate of filtration will decrease . 6 Some clinical applications about the filtration rate if there is any defect happen to the filtration membrane such as : if there is a damage in the podocytes , in the basement membrane ,or damage in the endothelial cells all of these may cause an increase in the permeability of the proteins so they will appear in the filtrate and the urine >>leading to protein loss , a condition called proteinuria (the presence of proteins in the urine ) in this case the liver couldn’t substitute protein loss and the blood oncotic pressure will drop and this will affect the capillary system in the body this will affect the filtration from the capillaries and the return to the circulation in the venous side due to the drop in the oncotic pressure so the result is edema (the fluid stays in the interstitial fluid ) . so that’s why the urine should be free from proteins it must have zero proteins . extra information ,in case of protein loss there will b 2 consequences: 1. increase NFP :the filtrate will exert a colloid osmotic pressure that draws water out of the blood this means (MORE FLUID IS FILTRATED ) 2. the blood colloid osmotic pressure will decrease , because plasma proteins are being lost in the urine.THIS LOSS ALSO CAUSE EDEMA AS WE SAID Why we were interested to know the normal GFR ? it is about 125 mL and have to remain constant If the GFR was too high , some substances will be filtrated faster than the kidney’s reabsorption ability ,in other words the rate of filtration exceeds the reabsorption rate ,so many valuable substances will be lost like water, minerals and electrolytes , (loss of valuable substances and drop in water volume ) But if the GFR decrease; the efficiency of kidney to eliminate waste products will decrease ,so the waste product will remain more time in our bodies , o the filtration in this case occur 40 times rather than 60 times o also the reabsorption will occur more efficiently than the filtration so may be a reabsorption of some waste products will occur ,that’s why we need to have a constant GFR in normal level . the factors that affect the GFR : the net filtration pressure(NFP) which directly proportional to the GFR >>so there is a constant( GFR= constant X NFP) ,this constant depend on hydraulic conductivity of the membrane this is physically , and usually this coefficient remain constant for the same person and varies from one to another ,and sometimes it may change in the same individual because of a certain disease occur in the membrane like the deposition of some fibrin 7 that will cause a change in the permeability of the membrane .also according to the previous equation this constant might be changed if the hydrostatic pressure (by the way the NFP)drop to 45 we will have zero NFP as well as zero GFR . actually this is not happen ,even if the hydrostatic pressure increase or decrease ,the GFR will remain constant contrary with the physical rules this what we will see if we measure the GFR practically in the kidney although, there is a fluctuation in the mean arterial pressure (and the hydrostatic pressure )in systole & diastole but the GFR remain constant .so this mean there is something which maintains GFR to keep the filtration rate constant or the flow rate inside the glomeruli constant and doesn’t change ,this is what happen in the auto regulation and this it is function . Done by : Noor Khanfar 8
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