Chapter Nephron 49 lm INTRODUCTION : zi SORPUSCLI . Re TUATION TYPES OF NEPHRON @ STRUCTURE lm TUBULAR PORTION OF NEPHRON = PROXIMAL CONVOLUTED TUBULE = LOOP OF HENLE fm DISTAL CONVOLUTED TUBULE @ COLLECTING DUCT PASSAGE OF URINE @ INTRODUCTION to 50 yoars of ago at the rate of 0.8% to Wy, Gvery year Each naphron its formed by two parts (Fig. 49.4) 1. A blind ond called renal corpuscle oF Malpightar Nephron is defined as the structural and functional unit of kidney. Each kidney consists of 1 to 1.3 millions of nephrons, corpusclo The number of nephrons starts decroasing alter about 45 2, tubular portion called renal tubule. Efferent arteriole Afferent arteriole --« Glomorulus Bowman capsule —~ Proximal convoluted ~~~ Distal convoluted tubule tubule Thick descending Thick ascending segment ‘oyna ; Go ee Thin ascending segment coor Collecting duct Hairpin bend FIGURE 49.1: Structure of nephron- g RENAL CORPUSCLE .enal corpuscle or Malpighian corpuscle is a spheroidal and slightly flattened structure with a diameter of about 200 v. Function of the renal corpuscle is the filtration of blood which forms the first phase of urine formation. g SITUATION OF RENAL CORPUSCLE AND TYPES OF NEPHRON Renal corpuscle is situated in the cortex of the kidney either near the periphery or near the medulla Classification of Nephrons Based on the situation of renal corpuscle, the nephrons are classified into two types: 4. Cortical nephrons or superficial nephrons: Nephrons having the corpuscles in outer cortex of the kidney near the periphery (Fig. 49.2). In human kidneys, 85% nephrons are cortical nephrons. Juxtamedullary / nephron Cortical ---" nephron --- Cortex Bectng — Outer medulla duct Duct of —Inner medulla petal ~ Renal sinus FIGURE 49.2: Types of nephron Chapter 49 @ Nephron 305 2. Juxtamedullary nephrons: Nephrons having the corpuscles in inner cortex near medulla or corticomedullary junction. Features of the two types of nephrons are given in Table 49.1. @ STRUCTURE OF RENAL CORPUSCLE Renal corpuscle is formed by two portions: 1. Glomerulus 2. Bowman capsule. Glomerulus Glomerulus is a tuft of capillaries enclosed by Bowman capsule. It consists of glomerular capillaries interposed between afferent arteriole on one end and efferent arteriole on the other end. Thus, the vascular system in the glomerulus is purely arterial (Fig. 49.3). Glomerular capillaries arise from the afferent arte- riole. After entering the Bowman capsule, the afferent Afferent arteriole — Efferent arteriole FIGURE 49.3; Renal corpuscle TABLE 49.1: Features of two types of nephron ies Percentage 85% Short Loop of Henle zone of medulla »d supply to tubule Peritubular capillaries Vasa recta Pies L : Mainly the concentration of urine and al {Furcton Formation of urine formation of urine oe | essa ivation of renal corpuscle Outer cortex near the periphery Hairpin bend penetrates only up to outer ene 15% Inner cortex near medulla Long Hairpin bend penetrates up to the tip of papillaCO ——— 306 Section 5 ¢ Renal Physiology and Skin arteriole divides into 4 or 5 large capillaries. Each large Apillary subdivides into many small capillaries. These Small capillaries are arranged in irregular loops and form anastomosis. All the smaller capillaries finally reunite 0 form the efferent arteriole, which leaves the Bowman capsule. Diameter of the efferent arteriole is less than that of afferent arteriole. This difference in diameter has got functional significance Functional histology Glomerular capillaries are made uy of single layer of endothelial cells, which are attached to Ki basoment membrane. Endothelium has many pores called fenestrae or filtration pores. Diameter of each pore is 0.1 . Presence of the fenestra is the evidence of the filtration function of the glomerulus. Bowman Capsule Bowman capsule is a capsular structure, which enclo- ses the glomerulus. Itis formed by two layers: i. Inner visceral layer ii, Outer parietal layer. Visceral layer covers the glomerular capillaries. It is continued as the parietal layer at the visceral pole. Parietal layer is continued with the wall of the tubular Portion of nephron. The cleft-ike space between the visceral and parietal layers is continued as the lumen of the tubular portion. Functional anatomy of Bowman capsule resembles a funnel with filter paper. Diameter of Bowman capsule is 200 p Functional histology Both the layers of Bowman capsule are composed of a single layer of flattened epithelial cells resting on a basement membrane. Basement membrane of the visceral layer fuses with the basement membrane of glomerular capillaries on which the capillary endothelial cells are arranged. Thus, the basement membranes, which are fused together, form the separation between the glomerular capillary endothelium and the epithelium of visceral layer of Bowman capsule. Epithelial cells of the visceral layer fuse with the basement membrane but the fusion is not complete. Each cell is connected with basement membrane by cytoplasmic extensions of epithelial cells called pedicles or feet. These pedicles are arranged in an interdigitating manner leaving small cleft-like spaces in between. The cleft-like space is called slit pore. Epithelial cells with pedicles are called podocytes (Fig. 49.4), Filtrate FIGURE 49.4: Fil embrené in formed by capillary endothelium on ons iayer of Bowman capsule (yellow) on TUBULAR PORTION OF NEPHRON Tubular portion of nephron is the continuation of Bow: capsule. Itis made up of three parts: 1. Proximal convoluted tubule 2. Loop of Henle 3. Distal convoluted tubule. ™ PROXIMAL CONVOLUTED TUBULE Proximal convoluted tubule is the coiled portion ars”: from Bowman capsule. It is situated in the cortex. continued as descending limb of loop of Henle. Li of proximal convoluted tubule is 14 mm and the dia is 55 p. Proximal convoluted tubule is continued 2s of Henle. Functional histology Proximal convoluted tubule is formed by single la Cuboidal epithelial cells. Characteristic feature of cells is the presence of hair-like projections dre? towards the lumen of the tubule. Because of Presence of these projections, the epithelial cel! called brush-bordered cells. @ LOOP OF HENLE Loop of Henle consists of: i. Descending limb ii. Hairpin bend ili, Ascending limb— : escending Limb 1, Descending ascending Hind of loop of Henle is made up of two ments sea Thick descending segment b. Thin descending segment, hick descending segment trick descending segment is the direct continuation of proximal convoluted tubule, It descends dawn into medulla. Ithas a length of 6 mm and a diameter of 55 4 formed by brush-bordered cuboidal epithelial c itis Thin descending segment Thick descending segment is continued as thin d cending segment (Fig. 49.5). It is formed by flattened epithelial cells without brush border and it is continued ag hairpin bend of the loop. ii, Hairpin Bend Hairpin bend formed by flattened epithelial cells without brush border and it is continued as the ascending limb of loop of Henle. j. Ascending Limb Ascending limb or segment of Henle loop has two parts: a. Thin ascending segment b. Thick ascending segment. Renal corpuscle Chapter 49 ¢ Nephron 307 Thin asconding segment Thin ascending segment is the continuation of hairpin bend. ILis also lined by flatloned epithelial colts without brush border Total length of thin descending segment, hairpin bend and thin nding sogment of Henle loop is ascending segment is continued as thick gment. conding segment Thick ascending segment is about 9 mm long with a diameter of 30 p. Thick ascending segment is lined by cuboidal epithelial cells without brush border, The terminal portion of thick ascending segment, which runs between the afferent and efferent arterioles, of the same nephrons forms the macula densa. Macula densa is the part of juxtaglomerular apparatus (Chapter 50). Thick ascending segment ascends to the cortex and continues as distal convoluted tubule. Length and Extent of Loop of Henle Length and the extent of the loop of Henle vary in different nephrons: i. In cortical nephrons, it is short and the hairpin bend penetrates only up to outer medulla Tubular portion | { | Proximal convoluted tubule Loop of Henle Distal convoluted tubule , t 1 Hairpin bend Ascending limb Descending limb 4 Thick descending Thin descending ‘segment segment FIGURE 49. Thin ascending —_Thick ascending segment segment | arts of nephron308 i Section 5 4 Renal Physiology and Skin Sern Bowman Capsule Proximal convoluted tubule ting duct TABLE 49,2: Size and cells of different parts of nephron and collecting rue ay er (mm) Flattened epithelium Thick descend Cuboidal cells with brush border : Be | Tapert Cuboidal cells with brush border in asco thet 1010 15 5 ane thin se Flattened epithelium | Cuboidal epithelium without brush border 9 x Cuboidal epithelium without brush border 14516 185 2 | Cuboidal epithelium without brush border 20 to 22 40 to. 209 | ii, In juxtamedullary Nephror Jux Ns, thi hairpin bend extends he ive ule deep ini In some ne ? into the inner medulla. Phrons it even Tuns up to the papilla. © DISTAL CONVOLUTED TUBULE Distal convoluted t ig duct. The length of the distal Fo noluted tubule is 14.5 to 15 mm. thas a diame: of 22 to 80 4 (Table 49,2) Functional histology Distal convoluted tub: cuboidal epithelial cell Cells in distal convolut cells (I cells). ule is lined by single layer of Is without brush border, Epithelial ited tubule are called intercalated @ COLLECTING pucT Distal convoluted tubule Continues as the initial or arched collecting duct, which is in cortex. The lower part of the collecting duct lies in medulla. Seven to ten initial Collecting ducts unite to form the straight collecting duct, which passes through medulla. Length of the collecting duct is 20 to 22 mm and its diameter varies between 40 and 200 u. Collecting duct is formed by cuboidal or columnar Pithelia, cells. Functional histology Collecting duct is formed by two types of epithelia cells: 1. Principal or P cells 2. Intercalated or I cells. These two types of cells have some functiona| Significance (Chapters 53 and 54), PASSAGE OF URINE Atthe inner zone of medulla, the straight Collecting ducts from each medullary pyramid unite to form papillary ducts or ducts of Bellini, which open into a 'V" shaped area Called papilla. Urine from each medullary pyrani is collected in the Papilla. From here it is drained intoa minor calyx. Three or four minor calyces unite to fom One major calyx. Each kidney has got about 8 mic calyces and 2 to 3 Major calyces. From minor Calyces urine Passes through maj! alyces, which open into the Pelvis of the ureter. Peis s the expanded portion of Ureter present in the renal sinus. From renal pelvis, urine Passes through remaining Portion of ureter and reaches urinary bladder.Juxtaglomerular Apparatus Chapter 50 @ DEFINITION @ STRUCTURE ™ MACULA DENSA @ =EXTRAGLOMERULAR MESANGIAL CELLS = JUXTAGLOMERULAR CELLS @ FUNCTIONS m SECRETION OF HORMONES ™ SECRETION OF OTHER SUBSTANCES @ REGULATION OF GLOMERULAR BLOOD FLOW AND GLOMERULAR FILTRATION RATE DEFINITION Juxtaglomerular apparatus is a specialized organ situated near the glomerulus of each nephron (juxta = near). © STRUCTURE OF JUXTAGLOMERULAR APPARATUS xtaglomerular apparatus is formed by three different uctures (Fig. 50.1): Macula densa Extraglomerular mesangial cells Juxtaglomerular cells. MACULA DENSA '-cula densa is the end portion of thick ascending * gment before it opens into distal convoluted tubule. | s situated between afferent and efferent arterioles of ‘3 same nephron. It is very close to afferent arteriole. Macula densa is formed by tightly packed cuboidal oithelial cells, * EXTRAGLOMERULAR MESANGIAL CELLS Extraglomerular mesangial cells are situated in the “angular region bound by afferent arteriole, efferent Sreriole and macula densa. These cells are also called *sranular cells, lacis cells or Goormaghtigh cells. Glomerular Mesangial Cells Besides extraglomerular mesangial cells there is another type of mesangial cells situated in between glomerular capillaries called glomerular mesangial or intraglomerular mesangial cells. Glomerular mesangial cells support the glomerular Capillary loops by surrounding the capillaries in the form of a cellular network. These cells play an important role in regulating the glomerular filtration by their contractile property, Macula densa [-77~7—> Thick ascending 1 segment Afferent __ ~ Efferent arteriole arteriole Juxtaglomerular——- — Extraglomerular cells mesangial cells ——- Glomerular mesangial cells FIGURE 50.1: Juxtaglomerular apparatusS10 Seetion § @ Renal Physiology and Skin Xomeniatl Mesangial cells ale phagoeytio i-mate. ase OWS also SeCIVtE glomeNilar interstitial matrix, prustagkantins and evtokines. ® JUXTAGLOMERULAR CELLS: Jentagiomerlat cells ate specialized: smooth muscle calls situated in the wall of afferent arteriote jist before it ators the Bowman capsule, These smooth muscle cells ane MUSti) prose iM unio Media and tunica adventitia of the wall of the afferent arteriole, Jextagionerulat galls ate also called granular cells decause of the presence of secretary granules in their evtoplasm Polar Cushion or Polkissen Juvtagioneruiar calls form a thick cuff called polar cushion of polkissen around the afferent arteriole defore it enters the Bowman capsule. @ FUNCTIONS OF JUXTAGLOMERULAR APPARATUS Primary funetion of juxtaglomerular apparatus is the secretion of hormones. It also regulates the glomerular dlood flow and glomerular filtration rate. ® SECRETION OF HORMONES Ju\taglomerular apparatus secretes two hormones: 1. Renin 2. Prostaglandin. 1. Renin Juxtaglomerular cells secrete renin. Renin is a peptide with 340 amino acids. Along with angiotensins, renin forms the renin-angiotensin system, which is a hormone system that plays an important role in the maintenance of blood pressure (Chapter 103). ‘Stimulants for renin secretion Secretion of renin is stimulated by four factors: |. Fall in arterial blood pressure ji, Reduction in the ECF volume li. Increased sympathetic activity 'v. Decreased load of sodium and chloride in macula densa. Renin-angiotensin system When renin is released into the blood, it acts on a specific plasma protein called angiotensinogen or renin substrate. It is the a,-globulin. By the activity of renin, the angiotensinogen is converted into a decapeptide > callad angiotensin | Angiotensin 1 Is convertag angiotensin UI, which is an octapeptide by the ch of anglotensin-converting enzyme (ACE) s¢¢,, fron lungs. Most of the conversion of angiotensin 1 angiotensin tH takes place in lungs. Angiotensin IH has a short half-life of about 4, minutes, Then itis rapidly degraded into a heptape, 2 called angiotensin I by angiotensinases, whic), * prosont in RBCs and vascular beds in many tiggug Angiotonsin Il is converted into angiotensin IV, which, av hexapoptide (Fig. 50.2). hy My Moy Inny Actions of Angiotensins: Angiotensin | Angiotensin | is physiologically inactive and serves gg, ‘as tho precursor of angiotensin I Angiotensin Il Angiotonsin Il is the most active form. Its actions are On blood vessels: i. Angiotensin 1! inereases arterial blood pressui, by directly acting on the blood vessels any causing vasoconstriction. Itis a potent constici, of arterioles. Earlier, when its other actions were not found it was called hypertensin. ii, It increases blood pressure indirectly , increasing the release of noradrenaline tron postganglionicsympathetic fibers. Noradrenaling is a general vasoconstrictor (Chapter 71). On adrenal cortex: It stimulates zona glomerulosa of adrenal cortex to secrete aldosterone. Aldosterone acts on renal tubules and increases retention of sodium, which is alo responsible for elevation of blood pressure. On kidney: i. Angiotensin Il regulates glomerular filtration ae by two ways: a. It constricts the efferent arteriole, whic causes decrease in filtration after an init increase (Chapter 52) b. It contracts the glomerular mesangial cels leading to decrease in surface area 9 glomerular capillaries and filtration (s# above) ii, It increases sodium reabsorption from ret! tubules. This action is more predominant proximal tubules. On brain: i. Angiotensin II inhibits the baroreceptor ree! and thereby indirectly increases the bye! pressure. Baroreceptor reflex is responsible o decreasing the blood pressure (Chapter 10 ”Chapter 50 # Juxtaglomeruiar Apparatus 311 Stimuli for renin secretion Plasma actions 4. Low blood pressure 2. Low ECF volume I 3, Sympathetic stimulation Angiotensinogen pit an 4, Low plasma sodi | jeguiates , um 2. Increases blood pressure 3. Increases water intake S nin 4. Increases ADH secretion 5. Increases CRH and ACTH secretion Angiotensin | Juxtaglomerular apparatus Angiotensinases | _ Angiotensin iv — FIGURE 50.2: Renin-angiotensin system. ECF = Extracellular fitration rate, ADH = Antidiuretic hormone, CRH = Corticotro ii. Itincreases water intake by stimulating the thirst center Itincreases the secretion of orticotropin-releasing hormone (CRH) from hypothalamus. CRH in tum increases secretion of adrenocorticotropic hormone (ACTH) from pituitary It increases secretion of antidiuretic hormone (ADH) from hypothalamus. iil, Other actions: Angiotensin Il acts as @ growth factor in heart and itis thought to cause muscular hypertrophy and cardiac enlargement. Angiotensin Ill Angiotensin Ill increases the blood pressure and stimulates aldosterone secretion from adrenal cortex. It has 100% adrenocortical stimulating activity and 40% vasopressor activity of angiotensin Il. Angiotensin IV It also has adrenocortical stimulating and vasopressor activities. i om a " ‘i Angiotensin i! —-> 1 1. Increase aldosterone secretion 2. Cause vasoconstriction fiuid, ACE = Angiotensin-converting enzyme, GFR = Glomerular pin-releasing hormone, ACTH = Adrenocorticotropic hormone. 2. Prostaglandin Extraglomerular mesangial cells of juxtaglomerular apparatus secrete prostaglandin. Prostaglandin is also secreted by interstitial cells of medulla called type ! medullary interstitial cells. Refer Chapter 72 for details. m SECRETION OF OTHER SUBSTANCES 1. Extraglomerular mesangial cells of juxtaglomerular apparatus secrete cytokines like interleukin-2 and tumor necrosis factor (Chapter 17) 2. Macula densa secretes thromboxane A. i REGULATION OF GLOMERULAR BLOOD FLOW AND GLOMERULAR FILTRATION RATE Macula densa of juxtaglomerular apparatus plays an important role in the feedback mechanism called tubuloglomerular feedback mechanism, which regulates the renal blood flow and glomerular filtration rate (Refer Chapter 52 for details).Chapter 52 INTRODUCTION GLOMERULAR FILTRATION ™ INTRODUCTION FILTRATION FRACTION FILTRATION COEFFICIENT TUBULAR REABSORPTION INTRODUCTION SELECTIVE REABSORPTION MECHANISM OF REABSORPTION ROUTES OF REABSORPTION SITE OF REABSORPTION THRESHOLD SUBSTANCES TUBULAR SECRETION @ INTRODUCTION SUMMARY OF URINE FORMATION METHOD OF COLLECTION OF GLOMERULAR FILTRATE GLOMERULAR FILTRATION RATE (GFR) PRESSURES DETERMINING FILTRATION FACTORS REGULATING (AFFECTING) GFR METHOD OF COLLECTION OF TUBULAR FLUID REGULATION OF TUBULAR REABSORPTION TRANSPORT MAXIMUM - Tm VALUE REABSORPTION OF IMPORTANT SUBSTANCES =m SUBSTANCES SECRETED IN DIFFERENT SEGMENTS OF RENAL TUBULES @ INTRODUCTION Urine formation is a blood cleansing function. Normally, about 1,300 mL of blood (26% of cardiac output) enters the kidneys. Kidneys excrete the unwanted substances along with water from the blood as urine. Normal urinary Cutput is 1 L/day to 1.5 Liday. Processes of Urine Formation When blood passes through glomerular capillaries, the plasma is filtered into the Bowman capsule. This process 'Scalled glomerular filtration. Filtrate from Bowman capsule passes through the tubular portion of the nephron. While passing through the tubule, the filtrate undergoes various changes both in quality and in quantity. Many wanted substances like glucose, amino acids, water and electrolytes are reabsorbed from the tubules. This process is called tubular reabsorption. And, some unwanted substances are secreted into the tubule from peritubular blood vessels. This process is called tubular secretion or excretion (Fig. 52.1). Thus, the urine formation includes three processes:316 Section 5 ¢ Renal Physiology and Skin Efferent Afferent arteriole arteriole Filtration Arterial blood Glomerulus ---—-' | Peritubular capillary Secretion Tubular portion-----} Venous blood Urine FIGURE 52.1: Events of urine formation A. Glomerular filtration B. Tubular reabsorption C. Tubular secretion. Among these three processes filtration is the function of the glomerulus. Reabsorption and secretion are the functions of tubular portion of the nephron. 1 GLOMERULAR FILTRATION = INTRODUCTION Glomerular filtration is the process by which the blood is filtered while passing through the glomerular capillaries by filtration membrane. It is the first process of urine formation. The structure of filtration membrane is well suited for filtration. Filtration Membrane Filtration membrane is formed by three layers: 1. Glomerular capillary membrane 2. Basement membrane 3. Visceral layer of Bowman capsule. 1. Glomerular capillary membrane Glomerular capillary membrane is formed by single layer of endothelial cells, which are attached to the basement membrane. The capillary membrane has many pores called fenestrae or filtration pores with a diameter of 0.1 p a 2. Basement membrane Basement membrane of glomerular capillaries the basement membrane of visceral layer of Boy” capsule fuse together. The fused basement Tembran separates the endothelium of glomerular capilary 51° the epithelium of visceral layer of Bowman capsule 3. Visceral layer of Bowman capsule This layer is formed by @ single layer of flattened en thelial cells resting on a basement membrane, Ean, call is connected with the basement membrane ¢ cytoplasmic extensions called pedicles or feet. Eth calls with pedicles are called podocytes (Refer to F 49.4), Pedicles interdigtate leaving small cet, spaces in between. The cleft-like space is called six pore or filtration slit. Filtration takes place thoy, these slit pores Process of Glomerular Filtration When blood passes through glomerular capilais the plasma is fitered into the Bowman capsule. All the substances of plasma are filtered except the plasma proteins. The filtered fluid is called glomerular filtrate Ultrafiltration Glomerular filtration is called ultrafiltration because ever the minute particles are filtered. But, the plasma proteirs are not filtered due to their large molecular size. The protein molecules are larger than the slit pores presen in the endothelium of capillaries. Thus, the glomeru: filtrate contains all the substances present in plasre except the plasma proteins. | METHOD OF COLLECTION OF GLOMERULAR FILTRATE Glomerular fitrate is collected in experimental animas by micropuncture technique. This technique involves insertion of a micropipette into the Bowman capsié and aspiration of fitrate. | GLOMERULAR FILTRATION RATE Glomerular fitration rate (GFR) is defined as the guantity of fitrate formed in all the nephrons of both & kidneys in the given unit of time. Normal GFR is 125 mL/minute or about 180 Lida! ™ FILTRATION FRACTION Filtration fraction is the fraction (portion) of the plasma, which becomes the filtrate. It is the- noon tonal plasttel Haw ane glomer iter tiltiation vate ol wwe prannedd 1 percentages yen mew OL ion Hawtin hoo piel Renal plasma tow Hy mit iain ~ 100 60 tdi et Normal fltaation farctlon vation HOM 15%. to 20% # PRESSURES DETERMINING FILTRATION prow, whleb determine the GER awe 1 Glomerular capillary prossure: ) Colloidal osmotic prossure in the glomeruli 4 Hydrostatic prossure in the Bowman capstile Those prossuirs determine the GFR by. either favoring oF opposing the filtration, {, Glomerular Capillary Prossuro Glomerular capillary prossure is the prossure oxertod by the blood in glomerular capillaries. His about 6O nm Hy and, varios botwoon 45 and 70: mm Hg, Glomerular ‘qpilary prossure is the highost capillary prossure in the body. [his pressure favors glomorutar titration 2, Colloidal Osmotic Pressure Its tho prossure exerted by plasma proteins. in the glomeruli. The plasma proteins are not filtered through the glomorular capillarios and romain in the glomerular cayitios. Those proteins develop the colloidal asnolle pressure, which is about 25 mm Hg, ILopposes: glomoralar filtration 4, iydrostatic Pressure in Bowman Capsule ILs tho pressure exerted by the filtrate in Bowman Gapsulo, ILis also called capsular prossure. |! Is about 18mm Hg. It also opposes glomerular filtration, Not Filtration Pressure Nol fitation prossuro is the balance between prossure favoring filtration and pressures opposing filtration. It '8 olhorwise known as effective filtration prossure or “ssontial filtration prossuro. Not filtration pressure Glomerular Colloidal Hyde capillary osmotic press plossure pressure Bowman capsule 60 (25015) © 20mm Ha Chapter 62 ¢ Urine Formation a7 Not filttation pressure is about 20-mm Hg and, tt vation betwoon 1h and 20: mm Hg Starling Hypothesis and Starling Forces Determination of net filtration pressure: bs based on Starling hypothosls, Starling hypothesis states that the hot fitation through capillary membrane is proportional to hydrostatic pressure differance across: the membrane inti oncatic prosaure differance, Hydrostatic prossture within the glomerular capillaries is the glomerular capillary prossure All the pressures: involved in determination of {iltvation are callod Starling forces. @ FILTRATION COEFFICIENT Filtration coofticiont is the GFR in terms of net filtration prossure. It is the GFR per mm Hg of not filtration prossure, For example, when GFR is 125 mL/min and not filtration prossure is 20 mm Hg 125 mt Filtration coefficient 20mm Hy 625 mbm Hy ™ FACTORS REGULATING (AFFECTING) GFR 1. Renal Blood Flow is tho most important factor that is necessary for glomorular filttation, GFR is directly proportional to renal blood flow, Normal blood flow to both the kidneys is 1,300 mL/minute. The renal blood flow itself is controlled by autorogulation, Refer previous chapter for dotails 2. Tubuloglomerular Feedback Tubuloglomerular feedback is the mechanism that regulatos GFR through renal tubule and macula densa (Fig. 52.2). Macula donsa of juxtaglomorular apparatus inthe terminal portion of thick ascending limb is sensitive to the sodium chloride in the tubular fluid When the glomerular filtrate passes through the terminal portion of thick ascending segment, macula donsa acts like a sensor. It detects the concentration of sodium chloride in the tubular fluid and accordingly alters the glomerular blood flow and GFR. Macula densa dotects the sodium chloride concentration via Na'-K* 2CI cotransporter (NKCC2), When the concentration of sodium chloride increases in the filtrate When GER increases, concentration of sodium chloride increasesinthe filtrate, Maculadensareleasesadenosine0 CR a 318 Section 5 # Renal Physiology and Skin Decrease in GFR Increase in GFR crease in NaC! concentration in renal tubule Macula densa Tubulaglomerular | feedback Adenosine tS Constriction of afferent arteriole Decrease in glomerular blood flow _—_——— FIGURE 52.2: Tubuloglomerular feedback. NaCl = Sodium chloride, GFR = Glomerular filtration rate. from ATP. Adenosine causes constriction of afferent arteriole. So the blood flow through glomerulus decreases leading to decrease in GFR. Adenosine acts on afferent arteriole via adenosine A, receptors. There are several other factors, which increase or decrease the sensitivity of tubuloglomerular feedback. Factors increasing the sensitivity of tubuloglo- merular feedback i. Adenosine ii. Thromboxane ii, Prostaglandin E, iv. Hydroxyeicosatetranoic acid Factors decreasing the sensitivity of tubuloglo- merular feedback: i. Atrial natriuretic peptide ii. Prostaglandin |, ili, Cyclic AMP (cAMP) iv. Nitrous oxide. When the concentration of sodium chloride decreases in the filtrate When GFR decreases, concentration of sodium chloride decreases in the filtrate. Macula densa secretes prostaglandin (PGE,), bradykinin and renin. PGE, and bradykinin cause dilatation of afferent arteriole. Renin induces the formation of angiotensin Il, which causes constriction of efferent arteriole. The afferent arteriole and constriction of fg dilatation of ease in glomerular blood fy, arteriole leads to incr GFR. ey aq 3. Glomerular Capillary Pressure ion rate is directly Proportion glomerular capillary Se EA Slomerye, ressure is 60 mm Hg. When glomery: Core pressure increases, the GFR also increas Conilary pressure, in turn depends upon the rena bs flow and arterial blood pressure. Glomerular filtra 4. Colloidal Osmotic Pressure filtration rate is inversely propor eons osmotic pressure, which is exerted plasma proteins in the glomerular capillary bj, Normal colloidal osmotic pressure is 25 mm Ha. Whey colloidal osmotic pressure increases as in the case dehydration or increased plasma protein leve| Grp decreases. When colloidal osmotic pressure is low as, hypoproteinemia, GFR increases. 5, Hydrostatic Pressure in Bowman Capsule GFR is inversely proportional to this. Normally, itis 4 mm Hg, When the hydrostatic pressure increases i the Bowman capsule, it decreases GFR. Hydrostat: pressure in Bowman capsule increases in conditers like obstruction of urethra and edema of kidney beneat renal capsule 6. Constriction of Afferent Arteriole Constriction of afferent arteriole reduces the blood fon to the glomerular capillaries, which in tum reduce GFR. 7. Constriction of Efferent Arteriole If efferent arteriole is constricted, initially the GFF increases because of stagnation of blood in tt capillaries. Later when all the substances are fite from this blood, further filtration does not occur. I because, the efferent arteriolar constriction preve outflow of blood from glomerulus and no fresh 0 enters the glomerulus for filtration. 8. Systemic Arterial Pressure Renal blood flow and GFR are not affected a8 !*" as the mean arterial blood pressure is in betwee" and 180 mm Hg due to the autoregulatory mechs (Chapter 51). Variation in pressure above 180 mmf below 60 mm Hg affects the renal blood flow andangy. vecause # ne atns the autoreg yond this range latory: mechanis ) anism ic Stimulation 7 ent artenoles are Su or ‘ e moderate stimulath cause any significant 9 sympatnel and effer nerves. The mild polied bY jon Chay pter 52 ¢ Urine Forination ng Egetors decreas" FR asiny GER by vasoconstriction |. Angiotensin I ii, Endothelins Noradrenaline platelet activate factor V plateletdonved growth {acto Prostaglan" (Pa LAR geanson?TiON 1 TuBU 1 wwrrodUcTiON Tubular reavsorpio" is the othel gupstances are (al pack 10 the dloo 4 tubuk portion of nepho" yt Lal ge i" The! ana -apsul? ue ih ow” «a to tne ow : “ nottio" in the wd ‘ es the wid the , ‘ a 1 red wil! ac on so! ep fe 4. gio0™ e or re 9° tes: 4 tes gti atte ek ue is Pps320 Section 5 ¢ Renal Physiology and Skin ™ SELECTIVE REABSORPTION Tubular reabsorption is known as selective reabsorption because the tubular cells reabsorb only the substances necessary for the body. Essential substances such as glucose, amino acids and vitamins are completely reabsorbed from renal tubule. Whereas the unwanted Substances like metabolic waste products are not reabsorbed and excreted through urine. ™ MECHANISM OF REABSORPTION Basic transport mechanisms reabsorption are of two types: 1. Active reabsorption 2. Passive reabsorption involved in tubular 1. Active Reabsorption Active reabsorption is the movement of molecules against the electrochemical (uphill) gradient. It needs liberation of energy, which is derived from ATP. Substances reabsorbed actively Substances reabsorbed actively from the renal tubule are sodium, calcium, potassium, phosphates, sulfates, bicarbonates, glucose, amino acids, ascorbic acid, uric acid and ketone bodies. 2. Passive Reabsorption Passive reabsorption is the movement of molecules along the electrochemical (downhill) gradient. This process does not need energy. Substances reabsorbed passively Substances reabsorbed passively are chloride, urea and water. ™ ROUTES OF REABSORPTION Reabsorption of substances from tubular lumen into the peritubular capillary occurs by two routes: 1. Trancelluar route 2. Paracellular route. 1. Transcellular Route In this route the substances move through the cell It includes transport of substances from: a. Tubular lumen into tubular cell through apical (luminal) surface of the cell membrane b. Tubular cell into interstitial fluid c. Interstitial fluid into capillary. Cp t— 7 2. Paracelluar Route In this route, the substances move throu intercellular space. It includes transport of substances from: i. Tubular lumen into interstitial fluid. pre, DH the Sent lateral intercellular space through the ,, ti junction between the cells ight ii. Interstitial fluid into capillary (Fig. 52.3), ™ SITE OF REABSORPTION Reabsorption of the substances occurs in almost all ing segments of tubular portion of nephron. 4. Substances Reabsorbed from Proximal Convoluted Tubule About 7/8 of the filtrate (about 88%) is reabsoy in proximal convoluted tubule. The brush border epithelial cells in proximal convoluted tubule increases the surface area and facilitates the reabsorption. ‘Substances reabsorbed from proximal convoluteg tubule are glucose, amino acids, sodium, potassium, calcium, bicarbonates, chlorides, phosphates, urea, uri: acid and water. 2. Substances Reabsorbed from Loop of Henle Substances reabsorbed from loop of Henle are sodium and chloride. 3. Substances Reabsorbed from Distal Convoluted Tubule Sodium, calcium, bicarbonate and water are reabsorbed from distal convoluted tubule. ™ REGULATION OF TUBULAR REABSORPTION Tubular reabsorption is regulated by three factors: FIGURE 52.3: Routes of reabsorption> : 4 Glomerulotubular balance ” Hormonal factors 3, Nervous factors. 4 Glomerulotubular Balance Glomerulotubular balance is the balance between the filtration and reabsorption of solutes and water in kidney. when GFR increases, the tubular load of solutes and water in the proximal convoluted tubule is increased. It jgfollowed by increase in the reabsorption of solutes and water. This process helps in the constant reabsorption of solute particularly sodium and water from renal tubule. Mechanism of glomerulotubular balance Glomerulotubular balance occurs because of osmotic pressure in the peritubular capillaries. When GFR increa- ses, more amount of plasma proteins accumulate in the glomerulus. Consequently, the osmotic pressure increa- ses in the blood by the time it reaches efferent arteriole and peritubular capillaries. The elevated osmotic pressure in the peritubular capillaries increases reabsorption of sodium and water from the tubule into the capillary blood. 2. Hormonal Factors Hormones, which regulate GFR are listed in Table 52.1. 3. Nervous Factor Activation of sympathetic nervous system increases the tubular reabsorption (particularly of sodium) from renal tubules. Italsoincreases the tubularreabsorptionindirectly by stimulating secretion of renin from juxtaglomerular cells, Renin causes formation of angiotensin II, which increases the sodium reabsorption (Chapter 50). | THRESHOLD SUBSTANCES Depending upon the degree of reabsorption, various Substances are classified into three categories: Chapter 52 @ Urine Formation 321 1, High-threshold substances 2. Low-threshold substances 3. Non-threshold substances. 1. High-threshold Substances High-threshold substances are those substances, which do not appear in urine under normal conditions. The food substances like glucose, amino acids, acetoacetate ions and vitamins are completely reabsorbed from renal tubules and do not appear in urine under normal conditions. These substances can appear in urine, only if their concentration in plasma is abnormally high or in renal diseases when reabsorption is affected. So, these substances are called high-threshold substances. 2. Low-threshold Substances Low-threshold substances are the substances, which appear in urine even under normal conditions. The substances such as urea, uric acid and phosphate are reabsorbed to a little extend. So, these substances appear in urine even under normal conditions. 3. Non-threshold Substances Non-threshold substances are those substances, which are not at all reabsorbed and are excreted in urine irrespective of their plasma level. The metabolic end products such as creatinine are the non-threshold substances. ™ TRANSPORT MAXIMUM — Tm VALUE Tubular transport maximum or Tm is the rate at which the maximum amount of a substance is reabsorbed from the renal tubule. . So, for every actively reabsorbed substance, there is a maximum rate at which it could be reabsorbed. For example, the transport maximum for glucose (TmG) is 375 mg/minute in adult males and about 300 mg/minute in adult females. jormones regulating tubular reabsorption