Renal Physiology and Skin PDF

Section Renal Physiology 5 and Skin 48. Kidney..................................................................................................... 301 49. Nephron......................................

Section Renal Physiology 5 and Skin 48. Kidney..................................................................................................... 301 49. Nephron.................................................................................................. 304 50. Juxtaglomerular Apparatus..................................................................... 309 51. Renal Circulation..................................................................................... 312 52. Urine Formation...................................................................................... 315 53. Concentration of Urine............................................................................ 325 54. Acidification of Urine and Role of Kidney in Acid-base Balance............. 330 55. Renal Function Tests............................................................................... 333 56. Renal Failure........................................................................................... 337 57. Micturition................................................................................................ 339 58. Dialysis and Artificial Kidney................................................................... 346 59. Diuretics.................................................................................................. 348 60. Structure of Skin...................................................................................... 351 61. Functions of Skin..................................................................................... 354 62. Glands of Skin......................................................................................... 356 63. Body Temperature................................................................................... 359  Chapter Kidney 48 „ INTRODUCTION „ FUNCTIONS OF KIDNEY „ ROLE IN HOMEOSTASIS „ HEMOPOIETIC FUNCTION „ ENDOCRINE FUNCTION „ REGULATION OF BLOOD PRESSURE „ REGULATION OF BLOOD CALCIUM LEVEL „ FUNCTIONAL ANATOMY OF KIDNEY „ DIFFERENT LAYERS OF KIDNEY „ TUBULAR STRUCTURES OF KIDNEY „ INTRODUCTION Renal system includes: 1. A pair of kidneys Excretion is the process by which the unwanted 2. Ureters substances and metabolic wastes are eliminated from 3. Urinary bladder the body. 4. Urethra. A large amount of waste materials and carbon di- Kidneys produce the urine. Ureters transport the oxide are produced in the tissues during metabolic urine to urinary bladder. Urinary bladder stores the urine process. In addition, residue of undigested food, until it is voided (emptied). Urine is voided from bladder heavy metals, drugs, toxic substances and pathogenic through urethra (Fig. 48.1). organisms like bacteria are also present in the body. All these substances must be removed to keep the „ FUNCTIONS OF KIDNEY body in healthy condition. Various systems/organs in the body are involved in performing the excretory function, viz. Kidneys perform several vital functions besides formation 1. Digestive system excretes food residues in the form of urine. By excreting urine, kidneys play the principal of feces. Some bacteria and toxic substances also role in homeostasis. Thus, the functions of kidney are: are excreted through feces 2. Lungs remove carbon dioxide and water vapor „ 1. ROLE IN HOMEOSTASIS 3. Skin excretes water, salts and some wastes. It also Primary function of kidneys is homeostasis. It is removes heat from the body accomplished by the formation of urine. During the 4. Liver excretes many substances like bile pigments, formation of urine, kidneys regulate various activities in heavy metals, drugs, toxins, bacteria, etc. through the body, which are concerned with homeostasis such bile. as: Although various organs are involved in removal of wastes from the body, their excretory capacity is limited. i. Excretion of Waste Products But renal system or urinary system has maximum excretory capacity and so it plays a major role in Kidneys excrete the unwanted waste products, which homeostasis. are formed during metabolic activities:  302 Section 5 t Renal Physiology and Skin organs, kidneys play major role in preventing acidosis. In fact, kidneys are the only organs, which are capable of eliminating certain metabolic acids like sulfuric and phosphoric acids. „ 2. HEMOPOIETIC FUNCTION Kidneys stimulate the production of erythrocytes by secreting erythropoietin. Erythropoietin is the important stimulating factor for erythropoiesis (Chapter 10). Kidney also secretes another factor called thrombopoietin, which stimulates the production of thrombocytes (Chapter 18). „ 3. ENDOCRINE FUNCTION Kidneys secrete many hormonal substances in addition to erythropoietin and thrombopoietin (Chapter 72). Hormones secreted by kidneys FIGURE 48.1: Urinary system i. Erythropoietin ii. Thrombopoietin a. Urea (end product of amino acid metabolism) iii. Renin b. Uric acid (end product of nucleic acid metabolism) iv. 1,25-dihydroxycholecalciferol (calcitriol) c. Creatinine (end product of metabolism in muscles) v. Prostaglandins. d. Bilirubin (end product of hemoglobin degradation) e. Products of metabolism of other substances. „ 4. REGULATION OF BLOOD PRESSURE Kidneys also excrete harmful foreign chemical Kidneys play an important role in the long-term regulation substances such as toxins, drugs, heavy metals of arterial blood pressure (Chapter 103) by two ways: pesticides, etc. i. By regulating the volume of extracellular fluid ii. Through renin-angiotensin mechanism. ii. Maintenance of Water Balance Kidneys maintain the water balance in the body by „ 5. REGULATION OF BLOOD CALCIUM LEVEL conserving water when it is decreased and excreting Kidneys play a role in the regulation of blood calcium water when it is excess in the body. This is an important level by activating 1,25-dihydroxycholecalciferol into process for homeostasis (Refer Chapter 4 for details). vitamin D. Vitamin D is necessary for the absorption of iii. Maintenance of Electrolyte Balance calcium from intestine (Chapter 68). Maintenance of electrolyte balance, especially sodium „ FUNCTIONAL ANATOMY OF KIDNEY is in relation to water balance. Kidneys retain sodium if the osmolarity of body water decreases and eliminate Kidney is a compound tubular gland covered by a sodium when osmolarity increases. connective tissue capsule. There is a depression on the medial border of kidney called hilum, through which iv. Maintenance of Acid–Base Balance renal artery, renal veins, nerves and ureter pass. The pH of the blood and body fluids should be „ DIFFERENT LAYERS OF KIDNEY maintained within narrow range for healthy living. It is achieved by the function of kidneys (Chapter 54). Body Components of kidney are arranged in three layers (Fig. is under constant threat to develop acidosis, because 48.2): of production of lot of acids during metabolic activities. 1. Outer cortex However, it is prevented by kidneys, lungs and blood 2. Inner medulla buffers, which eliminate these acids. Among these 3. Renal sinus.  Chapter 48 t Kidney 303 divided into 8 to 18 medullary or Malpighian pyramids. Broad base of each pyramid is in contact with cortex and the apex projects into minor calyx. 3. Renal Sinus Renal sinus consists of the following structures: i. Upper expanded part of ureter called renal pelvis ii. Subdivisions of pelvis: 2 or 3 major calyces and about 8 minor calyces iii. Branches of nerves, arteries and tributaries of veins iv. Loose connective tissues and fat. „ TUBULAR STRUCTURES OF KIDNEY Kidney is made up of closely arranged tubular structures FIGURE 48.2: Longitudinal section of kidney called uriniferous tubules. Blood vessels and interstitial connective tissues are interposed between these 1. Outer Cortex tubules. Uriniferous tubules include: Cortex is dark and granular in appearance. It contains 1. Terminal or secretary tubules called nephrons, renal corpuscles and convoluted tubules. At intervals, which are concerned with formation of urine cortical tissue penetrates medulla in the form of columns, 2. Collecting ducts or tubules, which are concerned which are called renal columns or columns of Bertini. with transport of urine from nephrons to pelvis of ureter. 2. Inner Medulla Collecting ducts unite to form ducts of Bellini, Medulla contains tubular and vascular structures which open into minor calyces through papilla. Other arranged in parallel radial lines. Medullary mass is details are given in Chapter 49.  Chapter Nephron 49 „ INTRODUCTION „ RENAL CORPUSCLE „ SITUATION – TYPES OF NEPHRON „ STRUCTURE „ TUBULAR PORTION OF NEPHRON „ PROXIMAL CONVOLUTED TUBULE „ LOOP OF HENLE „ DISTAL CONVOLUTED TUBULE „ COLLECTING DUCT „ PASSAGE OF URINE „ INTRODUCTION to 50 years of age at the rate of 0.8% to 1% every year. Each nephron is formed by two parts (Fig. 49.1): Nephron is defined as the structural and functional unit of 1. A blind end called renal corpuscle or Malpighian kidney. Each kidney consists of 1 to 1.3 millions of nephrons. corpuscle The number of nephrons starts decreasing after about 45 2. A tubular portion called renal tubule. FIGURE 49.1: Structure of nephron  Chapter 49 t Nephron 305 „ RENAL CORPUSCLE 2. Juxtamedullary nephrons: Nephrons having the corpuscles in inner cortex near medulla or Renal corpuscle or Malpighian corpuscle is a spheroidal corticomedullary junction. and slightly flattened structure with a diameter of about Features of the two types of nephrons are given in 200 µ. Table 49.1. Function of the renal corpuscle is the filtration of blood which forms the first phase of urine formation. „ STRUCTURE OF RENAL CORPUSCLE „ SITUATION OF RENAL CORPUSCLE AND Renal corpuscle is formed by two portions: TYPES OF NEPHRON 1. Glomerulus 2. Bowman capsule. Renal corpuscle is situated in the cortex of the kidney either near the periphery or near the medulla. Glomerulus Classification of Nephrons Glomerulus is a tuft of capillaries enclosed by Bowman capsule. It consists of glomerular capillaries interposed Based on the situation of renal corpuscle, the nephrons between afferent arteriole on one end and efferent are classified into two types: arteriole on the other end. Thus, the vascular system in 1. Cortical nephrons or superficial nephrons: Nephrons the glomerulus is purely arterial (Fig. 49.3). having the corpuscles in outer cortex of the kidney Glomerular capillaries arise from the afferent arte­ near the periphery (Fig. 49.2). In human kidneys, riole. After entering the Bowman capsule, the afferent 85% nephrons are cortical nephrons. FIGURE 49.2: Types of nephron FIGURE 49.3: Renal corpuscle TABLE 49.1: Features of two types of nephron Features Cortical nephron Juxtamedullary nephron Percentage 85% 15% Situation of renal corpuscle Outer cortex near the periphery Inner cortex near medulla Short Long Loop of Henle Hairpin bend penetrates only up to outer Hairpin bend penetrates up to the tip of papilla zone of medulla Blood supply to tubule Peritubular capillaries Vasa recta Mainly the concentration of urine and also Function Formation of urine formation of urine  306 Section 5 t Renal Physiology and Skin arteriole divides into 4 or 5 large capillaries. Each large capillary subdivides into many small capillaries. These small capillaries are arranged in irregular loops and form anastomosis. All the smaller capillaries finally reunite to 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 up of single layer of endothelial cells, which are attached to a basement membrane. Endothelium has many pores called fenestrae or filtration pores. Diameter of each pore is 0.1 µ. Presence of the fenestra is the evidence of the filtration function of the glomerulus. FIGURE 49.4: Filtering membrane in renal corpuscle. It is formed by capillary endothelium on one side (red) and visceral Bowman Capsule layer of Bowman capsule (yellow) on the other side. Bowman capsule is a capsular structure, which enclo­ ses the glomerulus. „ TUBULAR PORTION OF NEPHRON It is formed by two layers: i. Inner visceral layer Tubular portion of nephron is the continuation of Bowman ii. Outer parietal layer. capsule. Visceral layer covers the glomerular capillaries. It It is made up of three parts: is continued as the parietal layer at the visceral pole. 1. Proximal convoluted tubule Parietal layer is continued with the wall of the tubular 2. Loop of Henle portion of nephron. The cleft­like space between the 3. Distal convoluted tubule. visceral and parietal layers is continued as the lumen of the tubular portion. „ PROXIMAL CONVOLUTED TUBULE Functional anatomy of Bowman capsule resembles a funnel with filter paper. Diameter of Bowman capsule Proximal convoluted tubule is the coiled portion arising is 200 µ. from Bowman capsule. It is situated in the cortex. It is continued as descending limb of loop of Henle. Length Functional histology of proximal convoluted tubule is 14 mm and the diameter Both the layers of Bowman capsule are composed of is 55 µ. Proximal convoluted tubule is continued as loop a single layer of flattened epithelial cells resting on a of Henle. basement membrane. Basement membrane of the Functional histology visceral layer fuses with the basement membrane of glomerular capillaries on which the capillary endothelial Proximal convoluted tubule is formed by single layer of cells are arranged. Thus, the basement membranes, cuboidal epithelial cells. Characteristic feature of these which are fused together, form the separation between cells is the presence of hair­like projections directed the glomerular capillary endothelium and the epithelium towards the lumen of the tubule. Because of the of visceral layer of Bowman capsule. presence of these projections, the epithelial cells are Epithelial cells of the visceral layer fuse with the called brush-bordered cells. basement membrane but the fusion is not complete. Each cell is connected with basement membrane by „ LOOP OF HENLE cytoplasmic extensions of epithelial cells called pedicles or feet. These pedicles are arranged in an interdigitating Loop of Henle consists of: manner leaving small cleft­like spaces in between. The i. Descending limb cleft­like space is called slit pore. Epithelial cells with ii. Hairpin bend pedicles are called podocytes (Fig. 49.4). iii. Ascending limb.  Chapter 49 t Nephron 307 i. Descending Limb Thin ascending segment Descending limb of loop of Henle is made up of two Thin ascending segment is the continuation of hairpin segments: bend. It is also lined by flattened epithelial cells without a. Thick descending segment brush border. b. Thin descending segment. Total length of thin descending segment, hairpin Thick descending segment bend and thin ascending segment of Henle loop is 10 mm to 15 mm and the diameter is 15 µ. Thick descending segment is the direct continuation of Thin ascending segment is continued as thick the proximal convoluted tubule. It descends down into ascending segment. medulla. It has a length of 6 mm and a diameter of 55 µ. It is formed by brush­bordered cuboidal epithelial cells. Thick ascending segment Thin descending segment Thick ascending segment is about 9 mm long with a Thick descending segment is continued as thin des­ diameter of 30 µ. Thick ascending segment is lined by cending segment (Fig. 49.5). It is formed by flattened cuboidal epithelial cells without brush border. epithelial cells without brush border and it is continued The terminal portion of thick ascending segment, as hairpin bend of the loop. which runs between the afferent and efferent arterioles of the same nephrons forms the macula densa. Macula ii. Hairpin Bend densa is the part of juxtaglomerular apparatus (Chapter 50). Hairpin bend formed by flattened epithelial cells without Thick ascending segment ascends to the cortex brush border and it is continued as the ascending limb and continues as distal convoluted tubule. of loop of Henle. Length and Extent of Loop of Henle iii. Ascending Limb Ascending limb or segment of Henle loop has two Length and the extent of the loop of Henle vary in parts: different nephrons: a. Thin ascending segment i. In cortical nephrons, it is short and the hairpin bend b. Thick ascending segment. penetrates only up to outer medulla FIGURE 49.5: Parts of nephron  308 Section 5 t Renal Physiology and Skin TABLE 49.2: Size and cells of different parts of nephron and collecting duct Length Diameter Segment Epithelium (mm) (µ) Bowman Capsule Flattened epithelium ­ 200 Proximal convoluted tubule Cuboidal cells with brush border 14 55 Thick descending segment Cuboidal cells with brush border 6 55 Thin descending segment, hairpin bend 15 Flattened epithelium 10 to 15 and thin ascending segment Thick ascending segment Cuboidal epithelium without brush border 9 30 Distal convoluted tubule Cuboidal epithelium without brush border 14.5 to 15 22 to 50 Collecting duct Cuboidal epithelium without brush border 20 to 22 40 to 200 ii. In juxtamedullary nephrons, this is long and the duct is formed by cuboidal or columnar epithelial hairpin bend extends deep into the inner medulla. cells. In some nephrons it even runs up to the papilla. Functional histology „ DISTAL CONVOLUTED TUBULE Collecting duct is formed by two types of epithelial cells: Distal convoluted tubule is the continuation of thick ascending segment and occupies the cortex of kidney. 1. Principal or P cells It is continued as collecting duct. The length of the distal 2. Intercalated or I cells. convoluted tubule is 14.5 to 15 mm. It has a diameter of These two types of cells have some functional 22 to 50 µ (Table 49.2). significance (Chapters 53 and 54). Functional histology „ PASSAGE OF URINE Distal convoluted tubule is lined by single layer of At the inner zone of medulla, the straight collecting ducts cuboidal epithelial cells without brush border. Epithelial from each medullary pyramid unite to form papillary cells in distal convoluted tubule are called intercalated ducts or ducts of Bellini, which open into a ‘V’ shaped cells (I cells). area called papilla. Urine from each medullary pyramid is collected in the papilla. From here it is drained into a „ COLLECTING DUCT minor calyx. Three or four minor calyces unite to form Distal convoluted tubule continues as the initial or one major calyx. Each kidney has got about 8 minor arched collecting duct, which is in cortex. The lower part calyces and 2 to 3 major calyces. of the collecting duct lies in medulla. Seven to ten initial From minor calyces urine passes through major collecting ducts unite to form the straight collecting duct, calyces, which open into the pelvis of the ureter. Pelvis is which passes through medulla. the expanded portion of ureter present in the renal sinus. Length of the collecting duct is 20 to 22 mm and From renal pelvis, urine passes through remaining its diameter varies between 40 and 200 µ. Collecting portion of ureter and reaches urinary bladder.  Chapter Juxtaglomerular Apparatus 50 „ DEFINITION „ STRUCTURE „ MACULA DENSA „ EXTRAGLOMERULAR MESANGIAL CELLS „ JUXTAGLOMERULAR CELLS „ FUNCTIONS „ SECRETION OF HORMONES „ SECRETION OF OTHER SUBSTANCES „ REGULATION OF GLOMERULAR BLOOD FLOW AND GLOMERULAR FILTRATION RATE „ DEFINITION Glomerular Mesangial Cells Juxtaglomerular apparatus is a specialized organ Besides extraglomerular mesangial cells there is situated near the glomerulus of each nephron (juxta = another type of mesangial cells situated in between near). glomerular capillaries called glomerular mesangial or intraglomerular mesangial cells. „ STRUCTURE OF Glomerular mesangial cells support the glomerular JUXTAGLOMERULAR APPARATUS capillary loops by surrounding the capillaries in the form of a cellular network. Juxtaglomerular apparatus is formed by three different These cells play an important role in regulating structures (Fig. 50.1): the glomerular filtration by their contractile property. 1. Macula densa 2. Extraglomerular mesangial cells 3. Juxtaglomerular cells. „ MACULA DENSA Macula densa is the end portion of thick ascending segment before it opens into distal convoluted tubule. It is situated between afferent and efferent arterioles of the same nephron. It is very close to afferent arteriole. Macula densa is formed by tightly packed cuboidal epithelial cells. „ EXTRAGLOMERULAR MESANGIAL CELLS Extraglomerular mesangial cells are situated in the triangular region bound by afferent arteriole, efferent arteriole and macula densa. These cells are also called agranular cells, lacis cells or Goormaghtigh cells. FIGURE 50.1: Juxtaglomerular apparatus  310 Section 5 t Renal Physiology and Skin Glomerular mesangial cells are phagocytic in nature. called angiotensin I. Angiotensin I is converted into These cells also secrete glomerular interstitial matrix, angiotensin II, which is an octapeptide by the activity prostaglandins and cytokines. of angiotensin-converting enzyme (ACE) secreted from lungs. Most of the conversion of angiotensin I into „ JUXTAGLOMERULAR CELLS angiotensin II takes place in lungs. Angiotensin II has a short half-life of about 1 to 2 Juxtaglomerular cells are specialized smooth muscle minutes. Then it is rapidly degraded into a heptapeptide cells situated in the wall of afferent arteriole just before it called angiotensin III by angiotensinases, which are enters the Bowman capsule. These smooth muscle cells present in RBCs and vascular beds in many tissues. are mostly present in tunica media and tunica adventitia Angiotensin III is converted into angiotensin IV, which is of the wall of the afferent arteriole. a hexapeptide (Fig. 50.2). Juxtaglomerular cells are also called granular cells Actions of Angiotensins because of the presence of secretary granules in their cytoplasm. Angiotensin I Angiotensin I is physiologically inactive and serves only Polar Cushion or Polkissen as the precursor of angiotensin II. Juxtaglomerular cells form a thick cuff called polar Angiotensin II cushion or polkissen around the afferent arteriole Angiotensin II is the most active form. Its actions are: before it enters the Bowman capsule. On blood vessels: i. Angiotensin II increases arterial blood pressure „ FUNCTIONS OF by directly acting on the blood vessels and JUXTAGLOMERULAR APPARATUS causing vasoconstriction. It is a potent constrictor Primary function of juxtaglomerular apparatus is the of arterioles. Earlier, when its other actions were secretion of hormones. It also regulates the glomerular not found it was called hypertensin. blood flow and glomerular filtration rate. ii. It increases blood pressure indirectly by increasing the release of noradrenaline from „ SECRETION OF HORMONES postganglionic sympathetic fibers. Noradrenaline is a general vasoconstrictor (Chapter 71). Juxtaglomerular apparatus secretes two hormones: On adrenal cortex: 1. Renin 2. Prostaglandin. It stimulates zona glomerulosa of adrenal cortex to secrete aldosterone. Aldosterone acts on renal tubules 1. Renin and increases retention of sodium, which is also responsible for elevation of blood pressure. Juxtaglomerular cells secrete renin. Renin is a peptide On kidney: with 340 amino acids. Along with angiotensins, renin forms the renin-angiotensin system, which is a hormone i. Angiotensin II regulates glomerular filtration rate system that plays an important role in the maintenance by two ways: of blood pressure (Chapter 103). a. It constricts the efferent arteriole, which causes decrease in filtration after an initial Stimulants for renin secretion increase (Chapter 52) Secretion of renin is stimulated by four factors: b. It contracts the glomerular mesangial cells i. Fall in arterial blood pressure leading to decrease in surface area of ii. Reduction in the ECF volume glomerular capillaries and filtration (see above) iii. Increased sympathetic activity ii. It increases sodium reabsorption from renal iv. Decreased load of sodium and chloride in tubules. This action is more predominant on macula densa. proximal tubules. Renin-angiotensin system On brain: When renin is released into the blood, it acts on a i. Angiotensin II inhibits the baroreceptor reflex specific plasma protein called angiotensinogen or renin and thereby indirectly increases the blood substrate. It is the α2-globulin. By the activity of renin, pressure. Baroreceptor reflex is responsible for the angiotensinogen is converted into a decapeptide decreasing the blood pressure (Chapter 103)  Chapter 50 t Juxtaglomerular Apparatus 311 FIGURE 50.2: Renin-angiotensin system. ECF = Extracellular fluid, ACE = Angiotensin-converting enzyme, GFR = Glomerular filtration rate, ADH = Antidiuretic hormone, CRH = Corticotropin-releasing hormone, ACTH = Adrenocorticotropic hormone. ii. It increases water intake by stimulating the thirst 2. Prostaglandin center iii. It increases the secretion of orticotropin-releasing Extraglomerular mesangial cells of juxtaglomerular hormone (CRH) from hypothalamus. CRH in apparatus secrete prostaglandin. Prostaglandin is also turn increases secretion of adrenocorticotropic secreted by interstitial cells of medulla called type I hormone (ACTH) from pituitary medullary interstitial cells. Refer Chapter 72 for details. iv. It increases secretion of antidiuretic hormone (ADH) from hypothalamus. „ SECRETION OF OTHER SUBSTANCES Other actions: 1. Extraglomerular mesangial cells of juxtaglomerular Angiotensin II acts as a growth factor in heart and apparatus secrete cytokines like interleukin-2 and it is thought to cause muscular hypertrophy and cardiac tumor necrosis factor (Chapter 17) enlargement. 2. Macula densa secretes thromboxane A2. Angiotensin III „ REGULATION OF GLOMERULAR BLOOD Angiotensin III increases the blood pressure and FLOW AND GLOMERULAR FILTRATION RATE stimulates aldosterone secretion from adrenal cortex. It has 100% adrenocortical stimulating activity and 40% Macula densa of juxtaglomerular apparatus plays vasopressor activity of angiotensin II. an important role in the feedback mechanism called Angiotensin IV tubuloglomerular feedback mechanism, which regulates It also has adrenocortical stimulating and vasopressor the renal blood flow and glomerular filtration rate (Refer activities. Chapter 52 for details).  Chapter Renal Circulation 51 „ INTRODUCTION „ RENAL BLOOD VESSELS „ MEASUREMENT OF RENAL BLOOD FLOW „ REGULATION OF RENAL BLOOD FLOW „ AUTOREGULATION „ SPECIAL FEATURES OF RENAL CIRCULATION „ INTRODUCTION Blood vessels of kidneys are highly specialized to facilitate the functions of nephrons in the formation of urine. In the adults, during resting conditions both the kidneys receive 1,300 mL of blood per minute or about 26% of the cardiac output. Maximum blood supply to kidneys has got the functional significance. Renal arteries supply blood to the kidneys. „ RENAL BLOOD VESSELS FIGURE 51.1: Renal blood vessels Renal Artery Renal artery arises directly from abdominal aorta and Arcuate Artery enters the kidney through the hilus. While passing through renal sinus, the renal artery divides into many Each arcuate artery gives rise to interlobular arteries. segmental arteries. Interlobular Artery Segmental Artery Interlobular arteries run through the renal cortex perpendicular to arcuate artery. From each interlobular Segmental artery subdivides into interlobar arteries artery, numerous afferent arterioles arise. (Fig. 51.1). Afferent Arteriole Interlobar Artery Afferent arteriole enters the Bowman capsule and forms Interlobar artery passes in between the medullary glomerular capillary tuft. After entering the Bowman pyramids. At the base of the pyramid, it turns and runs capsule, the afferent arteriole divides into 4 or 5 large parallel to the base of pyramid forming arcuate artery. capillaries.  Chapter 51 t Renal Circulation 313 Glomerular Capillaries veins, interlobar veins, segmental veins and finally the renal vein (Fig. 51.3). Each large capillary divides into small glomerular Renal vein leaves the kidney through the hilus and capillaries, which form the loops. And, the capillary joins inferior vena cava. loops unite to form the efferent arteriole, which leaves the Bowman capsule. „ MEASUREMENT OF RENAL Efferent Arteriole BLOOD FLOW Efferent arterioles form a second capillary network Blood flow to kidneys is measured by using plasma called peritubular capillaries, which surround the tubular clearance of para-aminohippuric acid (Refer Chapter 55). portions of the nephrons. Thus, the renal circulation forms a portal system by the presence of two sets of „ REGULATION OF RENAL BLOOD FLOW capillaries namely glomerular capillaries and peritubular Renal blood flow is regulated mainly by autoregulation. capillaries. The nerves innervating renal blood vessels do not have any significant role in this. Peritubular Capillaries and Vasa Recta Peritubular capillaries are found around the tubular portion of cortical nephrons only. The tubular portion of juxtamedullary nephrons is supplied by some specialized capillaries called vasa recta. These capillaries are straight blood vessels hence the name vasa recta. Vasa recta arise directly from the efferent arteriole of the juxtamedullary nephrons and run parallel to the renal tubule into the medulla and ascend up towards the cortex (Fig. 51.2). Venous System Peritubular capillaries and vasa recta drain into the venous system. Venous system starts with peritubular venules and continues as interlobular veins, arcuate FIGURE 51.2: Renal capillaries FIGURE 51.3: Schematic diagram showing renal blood flow  314 Section 5 t Renal Physiology and Skin „ AUTOREGULATION „ SPECIAL FEATURES OF RENAL CIRCULATION Autoregulation is the intrinsic ability of an organ to regulate its own blood flow (Chapter 102). Autoregulation Renal circulation has some special features to cope up is present in some vital organs in the body such as with the functions of the kidneys. Such special features are: brain, heart and kidneys. It is highly significant and more 1. Renal arteries arise directly from the aorta. So, the efficient in kidneys. high pressure in aorta facilitates the high blood flow to the kidneys. Renal Autoregulation 2. Both the kidneys receive about 1,300 mL of blood Renal autoregulation is important to maintain the per minute, i.e. about 26% of cardiac output. Kidneys glomerular filtration rate (GFR). Blood flow to kidneys are the second organs to receive maximum blood remains normal even when the mean arterial blood flow, the first organ being the liver, which receives 1,500 mL per minute, i.e. about 30% of cardiac pressure vary widely between 60 mm Hg and 180 mm output. Hg. This helps to maintain normal GFR. 3. Whole amount of blood, which flows to kidney has Two mechanisms are involved in renal autoregulation: to pass through the glomerular capillaries before 1. Myogenic response entering the venous system. Because of this, the 2. Tubuloglomerular feedback. blood is completely filtered at the renal glomeruli. 4. Renal circulation has a portal system, i.e. a double 1. Myogenic Response network of capillaries, the glomerular capillaries and peritubular capillaries. Whenever the blood flow to kidneys increases, it 5. Renal glomerular capillaries form high pressure stretches the elastic wall of the afferent arteriole. bed with a pressure of 60 mm Hg to 70 mm Hg. It is Stretching of the vessel wall increases the flow of much greater than the capillary pressure elsewhere calcium ions from extracellular fluid into the cells. The in the body, which is only about 25 mm Hg to 30 mm influx of calcium ions leads to the contraction of smooth Hg. High pressure is maintained in the glomerular muscles in afferent arteriole, which causes constriction capillaries because the diameter of afferent arteriole of afferent arteriole. So, the blood flow is decreased. is more than that of efferent arteriole. The high capillary pressure augments glomerular filtration. 2. Tubuloglomerular Feedback 6. Peritubular capillaries form a low pressure bed with a pressure of 8 mm Hg to 10 mm Hg. This low Macula densa plays an important role in tubuloglomerular pressure helps tubular reabsorption. feedback, which controls the renal blood flow and GFR. 7. Autoregulation of renal blood flow is well Refer Chapter 52 for details. established.  Chapter Urine Formation 52 „ INTRODUCTION „ GLOMERULAR FILTRATION „ INTRODUCTION „ METHOD OF COLLECTION OF GLOMERULAR FILTRATE „ GLOMERULAR FILTRATION RATE (GFR) „ FILTRATION FRACTION „ PRESSURES DETERMINING FILTRATION „ FILTRATION COEFFICIENT „ FACTORS REGULATING (AFFECTING) GFR „ TUBULAR REABSORPTION „ INTRODUCTION „ METHOD OF COLLECTION OF TUBULAR FLUID „ SELECTIVE REABSORPTION „ MECHANISM OF REABSORPTION „ ROUTES OF REABSORPTION „ SITE OF REABSORPTION „ REGULATION OF TUBULAR REABSORPTION „ THRESHOLD SUBSTANCES TRANSPORT MAXIMUM – Tm VALUE „ REABSORPTION OF IMPORTANT SUBSTANCES „ TUBULAR SECRETION „ INTRODUCTION „ SUBSTANCES SECRETED IN DIFFERENT SEGMENTS OF RENAL TUBULES „ SUMMARY OF URINE FORMATION „ INTRODUCTION Filtrate from Bowman capsule passes through the tubular portion of the nephron. While passing through Urine formation is a blood cleansing function. Normally, about 1,300 mL of blood (26% of cardiac output) enters the tubule, the filtrate undergoes various changes both the kidneys. Kidneys excrete the unwanted substances in quality and in quantity. Many wanted substances along with water from the blood as urine. Normal urinary like glucose, amino acids, water and electrolytes are output is 1 L/day to 1.5 L/day. reabsorbed from the tubules. This process is called tubular reabsorption. Processes of Urine Formation And, some unwanted substances are secreted into When blood passes through glomerular capillaries, the the tubule from peritubular blood vessels. This process plasma is filtered into the Bowman capsule. This process is called tubular secretion or excretion (Fig. 52.1). is called glomerular filtration. Thus, the urine formation includes three processes:  316 Section 5 t Renal Physiology and Skin 2. Basement membrane Basement membrane of glomerular capillaries and the basement membrane of visceral layer of Bowman capsule fuse together. The fused basement membrane separates the endothelium of glomerular capillary and the epithelium of visceral layer of Bowman capsule. 3. Visceral layer of Bowman capsule This layer is formed by a single layer of flattened epi­ thelial cells resting on a basement membrane. Each cell is connected with the basement membrane by cytoplasmic extensions called pedicles or feet. Epithelial cells with pedicles are called podocytes (Refer to Fig. 49.4). Pedicles interdigitate leaving small cleft­like spaces in between. The cleft­like space is called slit pore or filtration slit. Filtration takes place through these slit pores. Process of Glomerular Filtration FIGURE 52.1: Events of urine formation When blood passes through glomerular capillaries, the plasma is filtered into the Bowman capsule. All the substances of plasma are filtered except the plasma A. Glomerular filtration proteins. The filtered fluid is called glomerular filtrate. B. Tubular reabsorption C. Tubular secretion. Ultrafiltration Among these three processes filtration is the function of the glomerulus. Reabsorption and secretion Glomerular filtration is called ultrafiltration because even are the functions of tubular portion of the nephron. the minute particles are filtered. But, the plasma proteins are not filtered due to their large molecular size. The „ GLOMERULAR FILTRATION protein molecules are larger than the slit pores present in the endothelium of capillaries. Thus, the glomerular „ INTRODUCTION filtrate contains all the substances present in plasma except the plasma proteins. Glomerular filtration is the process by which the blood is filtered while passing through the glomerular capillaries „ METHOD OF COLLECTION OF by filtration membrane. It is the first process of urine GLOMERULAR FILTRATE formation. The structure of filtration membrane is well suited for filtration. Glomerular filtrate is collected in experimental animals by micropuncture technique. This technique involves Filtration Membrane insertion of a micropipette into the Bowman capsule and aspiration of filtrate. Filtration membrane is formed by three layers: 1. Glomerular capillary membrane „ GLOMERULAR FILTRATION RATE 2. Basement membrane Glomerular filtration rate (GFR) is defined as the total 3. Visceral layer of Bowman capsule. quantity of filtrate formed in all the nephrons of both the 1. Glomerular capillary membrane kidneys in the given unit of time. Normal GFR is 125 mL/minute or about 180 L/day. Glomerular capillary membrane is formed by single layer of endothelial cells, which are attached to the „ FILTRATION FRACTION basement membrane. The capillary membrane has many pores called fenestrae or filtration pores with a Filtration fraction is the fraction (portion) of the renal diameter of 0.1 µ. plasma, which becomes the filtrate. It is the ratio  Chapter 52 t Urine Formation 317 between renal plasma flow and glomerular filtration rate. Net filtration pressure is about 20 mm Hg and, it It is expressed in percentage. varies between 15 and 20 mm Hg. GFR Filtration fraction = × 100 Starling Hypothesis and Starling Forces Renal plasma flow Determination of net filtration pressure is based on 125 mL/min Starling hypothesis. Starling hypothesis states that the = × 100 net filtration through capillary membrane is proportional 650 mL/min to hydrostatic pressure difference across the membrane = 19.2%. minus oncotic pressure difference. Hydrostatic pressure Normal filtration fraction varies from 15% to 20%. within the glomerular capillaries is the glomerular capillary pressure. „ PRESSURES DETERMINING FILTRATION All the pressures involved in determination of filtration are called Starling forces. Pressures, which determine the GFR are: 1. Glomerular capillary pressure „ FILTRATION COEFFICIENT 2. Colloidal osmotic pressure in the glomeruli 3. Hydrostatic pressure in the Bowman capsule. Filtration coefficient is the GFR in terms of net filtration These pressures determine the GFR by either pressure. It is the GFR per mm Hg of net filtration favoring or opposing the filtration. pressure. For example, when GFR is 125 mL/min and net filtration pressure is 20 mm Hg. 1. Glomerular Capillary Pressure 125 mL Glomerular capillary pressure is the pressure exerted Filtration coefficient = 20 mm Hg by the blood in glomerular capillaries. It is about 60 mm Hg and, varies between 45 and 70 mm Hg. Glomerular = 6.25 mL/mm Hg capillary pressure is the highest capillary pressure in the body. This pressure favors glomerular filtration. „ FACTORS REGULATING (AFFECTING) GFR 2. Colloidal Osmotic Pressure 1. Renal Blood Flow It is the pressure exerted by plasma proteins in the It is the most important factor that is necessary for glomeruli. The plasma proteins are not filtered through glomerular filtration. GFR is directly proportional to renal the glomerular capillaries and remain in the glomerular blood flow. Normal blood flow to both the kidneys is capillaries. These proteins develop the colloidal 1,300 mL/minute. The renal blood flow itself is controlled osmotic pressure, which is about 25 mm Hg. It opposes by autoregulation. Refer previous chapter for details. glomerular filtration. 2. Tubuloglomerular Feedback 3. Hydrostatic Pressure in Bowman Capsule Tubuloglomerular feedback is the mechanism that It is the pressure exerted by the filtrate in Bowman regulates GFR through renal tubule and macula densa capsule. It is also called capsular pressure. It is about (Fig. 52.2). Macula densa of juxtaglomerular apparatus 15 mm Hg. It also opposes glomerular filtration. in the terminal portion of thick ascending limb is sensitive to the sodium chloride in the tubular fluid. Net Filtration Pressure When the glomerular filtrate passes through the Net filtration pressure is the balance between pressure terminal portion of thick ascending segment, macula favoring filtration and pressures opposing filtration. It densa acts like a sensor. It detects the concentration is otherwise known as effective filtration pressure or of sodium chloride in the tubular fluid and accordingly essential filtration pressure. alters the glomerular blood flow and GFR. Macula densa Net filtration pressure = detects the sodium chloride concentration via Na+­K+­ 2Cl– cotransporter (NKCC2). When the concentration of sodium chloride increases in the filtrate When GFR increases, concentration of sodium chloride = 60 – (25 + 15) = 20 mm Hg. increases in the filtrate. Macula densa releases adenosine  318 Section 5 t Renal Physiology and Skin dilatation of afferent arteriole and constriction of efferent arteriole leads to increase in glomerular blood flow and GFR. 3. Glomerular Capillary Pressure Glomerular filtration rate is directly proportional to glomerular capillary pressure. Normal glomerular capillary pressure is 60 mm Hg. When glomerular capillary pressure increases, the GFR also increases. Capillary pressure, in turn depends upon the renal blood flow and arterial blood pressure. 4. Colloidal Osmotic Pressure Glomerular filtration rate is inversely proportional to colloidal osmotic pressure, which is exerted by plasma proteins in the glomerular capillary blood. Normal colloidal osmotic pressure is 25 mm Hg. When colloidal osmotic pressure increases as in the case of dehydration or increased plasma protein level GFR decreases. When colloidal osmotic pressure is low as in hypoproteinemia, GFR increases. FIGURE 52.2: Tubuloglomerular feedback. NaCl = Sodium chloride, GFR = Glomerular filtration rate. 5. Hydrostatic Pressure in Bowman Capsule GFR is inversely proportional to this. Normally, it is 15 from ATP. Adenosine causes constriction of afferent mm Hg. When the hydrostatic pressure increases in arteriole. So the blood flow through glomerulus the Bowman capsule, it decreases GFR. Hydrostatic decreases leading to decrease in GFR. Adenosine acts pressure in Bowman capsule increases in conditions on afferent arteriole via adenosine A1 receptors. like obstruction of urethra and edema of kidney beneath There are several other factors, which increase or renal capsule. decrease the sensitivity of tubuloglomerular feedback. Factors increasing the sensitivity of tubuloglo­ 6. Constriction of Afferent Arteriole merular feedback: i. Adenosine Constriction of afferent arteriole reduces the blood flow ii. Thromboxane to the glomerular capillaries, which in turn reduces iii. Prostaglandin E2 GFR. iv. Hydroxyeicosatetranoic acid. 7. Constriction of Efferent Arteriole Factors decreasing the sensitivity of tubuloglo­ merular feedback: If efferent arteriole is constricted, initially the GFR i. Atrial natriuretic peptide increases because of stagnation of blood in the ii. Prostaglandin I2 capillaries. Later when all the substances are filtered iii. Cyclic AMP (cAMP) from this blood, further filtration does not occur. It is iv. Nitrous oxide. because, the efferent arteriolar constriction prevents outflow of blood from glomerulus and no fresh blood When the concentration of sodium chloride enters the glomerulus for filtration. decreases in the filtrate When GFR decreases, concentration of sodium chloride 8. Systemic Arterial Pressure decreases in the filtrate. Macula densa secretes Renal blood flow and GFR are not affected as long prostaglandin (PGE2), bradykinin and renin. as the mean arterial blood pressure is in between 60 PGE2 and bradykinin cause dilatation of afferent and 180 mm Hg due to the autoregulatory mechanism arteriole. Renin induces the formation of angiotensin (Chapter 51). Variation in pressure above 180 mm Hg or II, which causes constriction of efferent arteriole. The below 60 mm Hg affects the renal blood flow and GFR  Chapter 52 t Urine Formation 319 accordingly, because the autoregulatory mechanism Factors decreasing GFR by vasoconstriction fails beyond this range. i. Angiotensin II 9. Sympathetic Stimulation ii. Endothelins iii. Noradrenaline Afferent and efferent arterioles are supplied by iv. Platelet­activating factor sympathetic nerves. The mild or moderate stimulation v. Platelet­derived growth factor of sympathetic nerves does not cause any significant change either in renal blood flow or GFR. vi. Prostaglandin (PGF2). Strong sympathetic stimulation causes severe constriction of the blood vessels by releasing the „ TUBULAR REABSORPTION neurotransmitter substance, noradrenaline. The effect is more severe on the efferent arterioles than on the „ INTRODUCTION afferent arterioles. So, initially there is increase in Tubular reabsorption is the process by which water and filtration but later it decreases. However, if the stimulation other substances are transported from renal tubules is continued for more than 30 minutes, there is recovery back to the blood. When the glomerular filtrate flows of both renal blood flow and GFR. It is because of through the tubular portion of nephron, both quantitative reduction in sympathetic neurotransmitter. and qualitative changes occur. Large quantity of water 10. Surface Area of Capillary Membrane (more than 99%), electrolytes and other substances are reabsorbed by the tubular epithelial cells. The GFR is directly proportional to the surface area of the reabsorbed substances move into the interstitial fluid capillary membrane. of renal medulla. And, from here, the substances move If the glomerular capillary membrane is affected as into the blood in peritubular capillaries. in the cases of some renal diseases, the surface area Since the substances are taken back into the blood for filtration decreases. So there is reduction in GFR. from the glomerular filtrate, the entire process is called tubular reabsorption. 11. Permeability of Capillary Membrane GFR is directly proportional to the permeability of „ METHOD OF COLLECTION OF TUBULAR FLUID glomerular capillary membrane. In many abnormal There are two methods to collect the tubular fluid for conditions like hypoxia, lack of blood supply, presence analysis. of toxic agents, etc. the permeability of the capillary membrane increases. In such conditions, even plasma 1. Micropuncture Technique proteins are filtered and excreted in urine. A micropipette is inserted into the Bowman capsule 12. Contraction of Glomerular Mesangial Cells and different parts of tubular portion in the nephrons Glomerular mesangial cells are situated in between the of experimental animals, to collect the fluid. The fluid glomerular capillaries. Contraction of these cells decrea­ samples are analyzed and compared with each other to ses surface area of capillaries resulting in reduction in assess the changes in different parts of nephron. GFR (refer Chapter 51 for details). 2. Stop-flow Method 13. Hormonal and Other Factors Ureter is obstructed so that the back pressure rises Many hormones and other secretory factors alter GFR and stops the glomerular filtration. The obstruction is by affecting the blood flow through glomerulus. continued for 8 minutes. It causes some changes in the fluid present in different parts of the tubular portion. Factors increasing GFR by vasodilatation Later, the obstruction is released and about 30 i. Atrial natriuretic peptide samples of 0.5 mL of urine are collected separately at ii. Brain natriuretic peptide regular intervals of 30 seconds. The first sample contains iii. cAMP the fluid from collecting duct. Successive samples iv. Dopamine contain the fluid from distal convoluted tubule, loops of v. Endothelial­derived nitric oxide Henle and proximal convoluted tubule respectively. All vi. Prostaglandin (PGE2). the samples are analyzed.  320 Section 5 t Renal Physiology and Skin „ SELECTIVE REABSORPTION 2. Paracelluar Route Tubular reabsorption is known as selective reabsorption In this route, the substances move through the because the tubular cells reabsorb only the substances intercellular space. necessary for the body. Essential substances such It includes transport of substances from: as glucose, amino acids and vitamins are completely i. Tubular lumen into interstitial fluid present in reabsorbed from renal tubule. Whereas the unwanted lateral intercellular space through the tight substances like metabolic waste products are not junction between the cells reabsorbed and excreted through urine. ii. Interstitial fluid into capillary (Fig. 52.3). „ MECHANISM OF REABSORPTION „ SITE OF REABSORPTION Basic transport mechanisms involved in tubular Reabsorption of the substances occurs in almost all the reabsorption are of two types: segments of tubular portion of nephron. 1. Active reabsorption 2. Passive reabsorption. 1. Substances Reabsorbed from Proximal Convoluted Tubule 1. Active Reabsorption About 7/8 of the filtrate (about 88%) is reabsorbed Active reabsorption is the movement of molecules in proximal convoluted tubule. The brush border of against the electrochemical (uphill) gradient. It needs epithelial cells in proximal convoluted tubule increases liberation of energy, which is derived from ATP. the surface area and facilitates the reabsorption. Substances reabsorbed from proximal convoluted Substances reabsorbed actively tubule are glucose, amino acids, sodium, potassium, Substances reabsorbed actively from the renal tubule calcium, bicarbonates, chlorides, phosphates, urea, uric are sodium, calcium, potassium, phosphates, sulfates, acid and water. bicarbonates, glucose, amino acids, ascorbic acid, uric acid and ketone bodies. 2. Substances Reabsorbed from Loop of Henle Substances reabsorbed from loop of Henle are sodium 2. Passive Reabsorption and chloride. Passive reabsorption is the movement of molecules along the electrochemical (downhill) gradient. This 3. Substances Reabsorbed from Distal process does not need energy. Convoluted Tubule Substances reabsorbed passively Sodium, calcium, bicarbonate and water are reabsorbed from distal convoluted tubule. Substances reabsorbed passively are chloride, urea and water. „ REGULATION OF TUBULAR REABSORPTION „ ROUTES OF REABSORPTION Tubular reabsorption is regulated by three factors: 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. FIGURE 52.3: Routes of reabsorption  Chapter 52 t Urine Formation 321 1. Glomerulotubular balance 1. High­threshold substances 2. Hormonal factors 2. Low­threshold substances 3. Nervous factors. 3. Non­threshold substances. 1. Glomerulotubular Balance 1. High-threshold Substances Glomerulotubular balance is the balance between the High­threshold substances are those substances, which filtration and reabsorption of solutes and water in kidney. do not appear in urine under normal conditions. The food When GFR increases, the tubular load of solutes and substances like glucose, amino acids, acetoacetate water in the proximal convoluted tubule is increased. It ions and vitamins are completely reabsorbed from is followed by increase in the reabsorption of solutes and renal tubules and do not appear in urine under normal water. This process helps in the constant reabsorption of conditions. These substances can appear in urine, only solute particularly sodium and water from renal tubule. if their concentration in plasma is abnormally high or in renal diseases when reabsorption is affected. So, these Mechanism of glomerulotubular balance substances are called high­threshold substances. Glomerulotubular balance occurs because of osmotic 2. Low-threshold Substances pressure in the peritubular capillaries. When GFR increa­ ses, more amount of plasma proteins accumulate in the Low­threshold substances are the substances, which glomerulus. Consequently, the osmotic pressure increa­ appear in urine even under normal conditions. The ses in the blood by the time it reaches efferent arteriole substances such as urea, uric acid and phosphate are and peritubular capillaries. The elevated osmotic pressure reabsorbed to a little extend. So, these substances in the peritubular capillaries increases reabsorption of appear in urine even under normal conditions. sodium and water from the tubule into the capillary blood. 3. Non-threshold Substances 2. Hormonal Factors Non­threshold substances are those substances, Hormones, which regulate GFR are listed in Table 52.1. which are not at all reabsorbed and are excreted in urine irrespective of their plasma level. The metabolic 3. Nervous Factor end products such as creatinine are the non­threshold substances. Activation of sympathetic nervous system increases the tubular reabsorption (particularly of sodium) from renal TRANSPORT MAXIMUM – Tm VALUE tubules. It also increases the tubular reabsorption indirectly by stimulating secretion of renin from juxtaglomerular Tubular transport maximum or Tm is the rate at which cells. Renin causes formation of angiotensin II, which the maximum amount of a substance is reabsorbed increases the sodium reabsorption (Chapter 50). from the renal tubule. So, for every actively reabsorbed substance, there „ THRESHOLD SUBSTANCES is a maximum rate at which it could be reabsorbed. For example, the transport maximum for glucose (TmG) is Depending upon the degree of reabsorption, various 375 mg/minute in adult males and about 300 mg/minute substances are classified into three categories: in adult females. TABLE 52.1: Hormones regulating tubular reabsorption Hormone Action Aldosterone Increases sodium reabsorption in ascending limb, distal convoluted tubule and collecting duct Increases sodium reabsorption in proximal tubule, thick ascending limb, distal tubule and Angiotensin II collecting duct (mainly in proximal convoluted tubule) Antidiuretic hormone Increases water reabsorption in distal convoluted tubule and collecting duct Atrial natriuretic factor Decreases sodium reabsorption Brain natriuretic factor Decreases sodium reabsorption Increases reabsorption of calcium, magnesium and hydrogen Parathormone Decreases phosphate reabsorption Calcitonin Decreases calcium reabsorption  322 Section 5 t Renal Physiology and Skin Threshold Level in Plasma for Substances from the cell into interstitium and two potassium ions having Tm Value from interstitium into the cell. Tubular epithelial cells are connected with their Renal threshold is the plasma concentration at which neighboring cells by tight junctions at their apical luminal a substance appears in urine. Every substance having edges. But, beyond the tight junction, a small space Tm value has also a threshold level in plasma or blood. is left between the adjoining cells along their lateral Below that threshold level, the substance is completely borders. This space is called lateral intercellular space. reabsorbed and does not appear in urine. When the The interstitium extends into this space. concentration of that substance reaches the threshold, Most of the sodium ions are pumped into the lateral the excess amount is not reabsorbed and, so it appears intercellular space by sodium­potassium pump. The rest in urine. This level is called the renal threshold of that of the sodium ions are pumped into the interstitium by substance. the sodium­potassium pump situated at the basal part For example, the renal threshold for glucose is 180 of the cell membrane. mg/dL. That is, glucose is completely reabsorbed from (Transport of sodium out of the tubular cell by sodium­ tubular fluid if its concentration in blood is below 180 potassium pump, decreases the sodium concentration mg/dL. So, the glucose does not appear in urine. When within the cell. This develops an electrochemical gradient the blood level of glucose reaches 180 mg/dL it is not between the lumen and tubular cell resulting in diffusion reabsorbed completely; hence it appears in urine. of sodium into the cell). „ REABSORPTION OF IMPORTANT SUBSTANCES 3. Transport from Interstitial Fluid to the Blood Reabsorption of Sodium From the interstitial fluid, sodium ions enter the From the glomerular filtrate, 99% of sodium is reabsor­ peritubular capillaries by concentration gradient. bed. Two thirds of sodium is reabsorbed in proximal In the distal convoluted tubule, the sodium re­ convoluted tubule and remaining one third in other seg­ absorption is stimulated by the hormone aldosterone ments (except descending limb) and collecting duct. secreted by adrenal cortex. Sodium reabsorption occurs in three steps: 1. Transport from lumen of renal tubules into the Reabsorption of Water tubular epithelial cells Reabsorption of water occurs from proximal and distal 2. Transport from tubular cells into the interstitial fluid convoluted tubules and in collecting duct. 3. Transport from interstitial fluid to the blood. Reabsorption of water from proximal convoluted 1. Transport from Lumen of Renal Tubules tubule – obligatory water reabsorption into the Tubular Epithelial Cells Obligatory reabsorption is the type of water reabsorption Active reabsorption of sodium ions from lumen into the in proximal convoluted tubule, which is secondary tubular cells occurs by two ways: (obligatory) to sodium reabsorption. When sodium i. In exchange for hydrogen ion by antiport (sodium is reabsorbed from the tubule, the osmotic pressure counterport protein) – in proximal convoluted decreases. It causes osmosis of water from renal tubules tubule. ii. Along with other substances like glucose and Reabsorption of water from distal convoluted tubule amino acids by symport (sodium co­transport and collecting duct – facultative water reabsorption protein) – in other segments and collecting duct. Facultative reabsorption is the type of water reabsorption It is believed that some amount of sodium diffuses in distal convoluted tubule and collecting duct that along the electrochemical gradient from lumen into occurs by the activity of antidiuretic hormone (ADH). tubular cell across the luminar membrane. The electro­ chemical gradient is developed by sodium­potassium Normally, the distal convoluted tubule and the collecting pump (see below). duct are not permeable to water. But in the presence of ADH, these segments become permeable to water, so it is reabsorbed. 2. Transport from Tubular Cells into the Interstitial Fluid Mechanism of action of ADH – Aquaporins Sodium is pumped outside the cells by sodium­ Antidiuretic hormone increases water reabsorption potassium pump. This pump moves three sodium ions in distal convoluted tubules and collecting ducts by  Chapter 52 t Urine Formation 323 stimulating the water channels called aquaporins. ADH combines with vasopressin (V2) receptors in the tubular epithelial membrane and activates adenyl cyclase, to form cyclic AMP. This cyclic AMP activates the aquaporins, which increase the water reabsorption. Aquaporins (AQP) are the membrane proteins, which function as water channels. Though about 10 aquaporins are identified in mammals only 5 are found in humans. Aquaporin­1, 2 and 3 are present in renal tubules. Aquaporin­4 is present in brain and aquaporin­5 is found in salivary glands. Aquaporin­2 forms the water channels in renal tubules. Reabsorption of Glucose Glucose is completely reabsorbed in the proximal convoluted tubule. It is transported by secondary active transport (sodium cotransport) mechanism. Glucose and sodium bind to a common carrier protein in the luminal FIGURE 52.4: Splay in renal threshold curve for glucose membrane of tubular epithelium and enter the cell. The carrier protein is called sodium-dependant glucose Reabsorption of Bicarbonates cotransporter 2 (SGLT2). From tubular cell glucose is transported into medullary interstitium by another carrier Bicarbonate is reabsorbed actively, mostly in proximal protein called glucose transporter 2 (GLUT2). tubule (Chapter 54). It is reabsorbed in the form of carbon dioxide. Tubular maximum for glucose (TmG) Bicarbonate is mostly present as sodium bicarbonate In adult male, TmG is 375 mg/minute and in adult in the filtrate. Sodium bicarbonate dissociates into sodium females it about 300 mg/minute. and bicarbonate ions in the tubular lumen. Sodium diffuses into tubular cell in exchange of hydrogen. Renal threshold for glucose Bicarbonate combines with hydrogen to form carbonic Renal threshold for glucose is 180 mg/dL in venous acid. Carbonic acid dissociates into carbon dioxide and blood. When the blood level reaches 180 mg/dL glucose water in the presence of carbonic anhydrase. Carbon is not reabsorbed completely and appears in urine. dioxide and water enter the tubular cell. In the tubular cells, carbon dioxide combines with Splay water to form carbonic acid. It immediately dissociates Splay means deviation. With normal GFR of 125 mL/ into hydrogen and bicarbonate. Bicarbonate from the minute and TmG of 375 mg/minute in an adult male the tubular cell enters the interstitium. There it combines predicted (expected) renal threshold for glucose should with sodium to form sodium bicarbonate (Fig. 54.1). be 300 mg/dL. But actually it is only 180 mg/dL. When the renal threshold curves are drawn by using „ TUBULAR SECRETION these values, the actual curve deviates from the ‘should be’ or predicted or ideal curve (Fig. 52.4). This type of „ INTRODUCTION deviation is called splay. Splay is because of the fact Tubular secretion is the process by which the substances that all the nephrons do not have the same filtering and are transported from blood into renal tubules. It is also reabsorbing capacities. called tubular excretion. In addition to reabsorption from renal tubules, some substances are also secreted into Reabsorption of Amino Acids the lumen from the peritubular capillaries through the Amino acids are also reabsorbed completely in proximal tubular epithelial cells. convoluted tubule. Amino acids are reabsorbed actively Dye phenol red was the first substance found to be by the secondary active transport mechanism along secreted in renal tubules in experimental conditions. with sodium. Later many other substances were found to be secreted.  324 Section 5 t Renal Physiology and Skin Such substances are: Thus, urine is formed in nephron by the processes of 1. Para­aminohippuric acid (PAH) glomerular filtration, selective reabsorption and tubular secretion. 2. Diodrast 3. 5­hydroxyindoleacetic acid (5­HIAA) „ SUMMARY OF URINE FORMATION 4. Amino derivatives 5. Penicillin. Urine formation takes place in three processes (Refer to Fig. 52.1): „ SUBSTANCES SECRETED IN DIFFERENT 1. Glomerular filtration SEGMENTS OF RENAL TUBULES Plasma is filtered in glomeruli and the substances reach 1. Potassium is secreted actively by sodium­potassium the renal tubules along with water as filtrate. pump in proximal and distal convoluted tubules and 2. Tubular Reabsorption collecting ducts 2. Ammonia is secreted in the proximal convoluted The 99% of filtrate is reabsorbed in different segments of renal tubules. tubule 3. Hydrogen ions are secreted in the proximal and 3. Tubular Secretion distal convoluted tubules. Maximum hydrogen ion Some substances are transported from blood into the secretion occurs in proximal tubule renal tubule. 4. Urea is secreted in loop of Henle. With all these changes, the filtrate becomes urine.  Chapter Concentration of Urine 53 „ INTRODUCTION „ MEDULLARY GRADIENT „ COUNTERCURRENT MECHANISM „ ROLE OF ADH „ SUMMARY OF URINE CONCENTRATION „ APPLIED PHYSIOLOGY „ INTRODUCTION tion of concentrated urine is not as simple as that of dilute urine. Every day 180 L of glomerular filtrate is formed with large It involves two processes: quantity of water. If this much of water is excreted in 1. Development and maintenance of medullary urine, body will face serious threats. So the concentration gradient by countercurrent system of urine is very essential. 2. Secretion of ADH. Osmolarity of glomerular filtrate is same as that of plasma and it is 300 mOsm/L. But, normally urine is „ MEDULLARY GRADIENT concentrated and its osmolarity is four times more than that of plasma, i.e. 1,200 mOsm/L. „ MEDULLARY HYPEROSMOLARITY Osmolarity of urine depends upon two factors: 1. Water content in the body Cortical interstitial fluid is isotonic to plasma with the 2. Antidiuretic hormone (ADH). osmolarity of 300 mOsm/L. Osmolarity of medullary Mechanism of urine formation is the same for interstitial fluid near the cortex is also 300 mOsm/L. dilute urine and concentrated urine till the fluid reaches However, while proceeding from outer part towards the distal convoluted tubule. However, dilution or the inner part of medulla, the osmolarity increases concentration of urine depends upon water content of gradually and reaches the maximum at the inner most the body. part of medulla near renal sinus. Here, the interstitial fluid is hypertonic with osmolarity of 1,200 mOsm/L (Fig. „ FORMATION OF DILUTE URINE 53.1). This type of gradual increase in the osmolarity of When, water content in the body increases, kidney the medullary interstitial fluid is called the medullary excretes dilute urine. This is achieved by inhibition of gradient. It plays an important role in the concentration ADH secretion from posterior pituitary (Chapter 66). of urine. So water reabsorption from renal tubules does not take place (see Fig. 53.4) leading to excretion of large „ DEVELOPMENT AND MAINTENANCE OF amount of water. This makes the urine dilute. MEDULLARY GRADIENT Kidney has some unique mechanism called counter­ „ FORMATION OF CONCENTRATED URINE current mechanism, which is responsible for the develop­ When the water content in body decreases, kidney ment and maintenance of medullary gradient and hyper­ retains water and excretes concentrated urine. Forma­ osmolarity of interstitial fluid in the inner medulla.  326 Section 5 t Renal Physiology and Skin Role of Loop of Henle in Development of Medullary Gradient Loop of Henle of juxtamedullary nephrons plays a major role as countercurrent multiplier because loop of these nephrons is long and extends upto the deeper parts of medulla. Main reason for the hyperosmolarity of medullary interstitial fluid is the active reabsorption of sodium chloride and other solutes from ascending limb of Henle loop into the medullary interstitium. These solutes accumulate in the medullary interstitium and increase the osmolarity. Now, due to the concentration gradient, the sodium and chlorine ions diffuse from medullary interstitium into the descending limb of Henle loop and reach the ascending limb again via hairpin bend. Thus, the sodium and chlorine ions are repeatedly re­