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Chapter 26 The Urinary System Lecture Outline Principles of Human Anatomy and Physiology, 11e 1 INTRODUCTION • The urinary system consists of two kidneys, two ureters, one urinary bladder, and one urethra (Figure 26.1). • Urine is excreted from each kidney through its ureter and is stored in the urinary bladder until it is expelled from the body through the urethra. • The specialized branch of medicine that deals with structure, function, and diseases of the male and female urinary systems and the male reproductive system is known as nephrology. The branch of surgery related to male and female urinary systems and the male reproductive system is called urology. Principles of Human Anatomy and Physiology, 11e 2 Chapter 26 The Urinary System • Kidneys, ureters, urinary bladder & urethra • Urine flows from each kidney, down its ureter to the bladder and to the outside via the urethra • Filter the blood and return most of water and solutes to the bloodstream Principles of Human Anatomy and Physiology, 11e 3 Overview of Kidney Functions • Regulation of blood ionic composition – Na+, K+, Ca+2, Cl- and phosphate ions • Regulation of blood pH, osmolarity & glucose • Regulation of blood volume – conserving or eliminating water • Regulation of blood pressure – secreting the enzyme renin – adjusting renal resistance • Release of erythropoietin & calcitriol • Excretion of wastes & foreign substances Principles of Human Anatomy and Physiology, 11e 4 ANATOMY AND HISTOLOGY OF THE KIDNEYS • The paired kidneys are retroperitoneal organs (Figure 26.2). Principles of Human Anatomy and Physiology, 11e 5 External Anatomy of the Kidney • Near the center of the concave medial border of the kidney is a vertical fissure called the hilus, through which the ureter leaves and blood vessels, lymphatic vessels, and nerves enter and exit (Figure 26.3). • Three layers of tissue surround each kidney: the innermost renal capsule, the adipose capsule, and the outer renal fascia. • Nephroptosis is an inferior displacement of the kidneys. It most often occurs in thin people. This condition is dangerous because the ureters may kink and block urine flow (Clinical Application). Principles of Human Anatomy and Physiology, 11e 6 External Anatomy of Kidney • Paired kidney-bean-shaped organ • 4-5 in long, 2-3 in wide, 1 in thick • Found just above the waist between the peritoneum & posterior wall of abdomen – retroperitoneal (along with adrenal glands & ureters) • Protected by 11th & 12th ribs with right kidney lower Principles of Human Anatomy and Physiology, 11e 7 External Anatomy of Kidney • • • • Blood vessels & ureter enter hilus of kidney Renal capsule = transparent membrane maintains organ shape Adipose capsule that helps protect from trauma Renal fascia = dense, irregular connective tissue that holds against back body wall Principles of Human Anatomy and Physiology, 11e 8 External Anatomy of Kidney Principles of Human Anatomy and Physiology, 11e 9 Internal Anatomy of the Kidney • Internally, the kidneys consist of cortex, medulla, pyramids, papillae, columns, calyces, and pelves (Figure 26.3). • The renal cortex and renal pyramids constitute the functional portion or parenchyma of the kidney. • The nephron is the functional unit of the kidney. Principles of Human Anatomy and Physiology, 11e 10 Internal Anatomy of the Kidneys • Parenchyma of kidney – renal cortex = superficial layer of kidney – renal medulla • inner portion consisting of 8-18 cone-shaped renal pyramids separated by renal columns • renal papilla point toward center of kidney • Drainage system fills renal sinus cavity – cuplike structure (minor calyces) collect urine from the papillary ducts of the papilla – minor & major calyces empty into the renal pelvis which empties into the ureter Principles of Human Anatomy and Physiology, 11e 11 Internal Anatomy of Kidney • What is the difference between renal hilus & renal sinus? • Outline a major calyx & the border between cortex & medulla. Principles of Human Anatomy and Physiology, 11e 12 Blood and Nerve Supply of the Kidneys • Blood enters the kidney through the renal artery and exits via the renal vein. – Figures 26.4 and 26.5 show the branching pattern of renal blood vessels and the path of blood flow through the kidneys. • In a kidney transplant a donor kidney is placed in the pelvis of the recipient through an abdominal incision. The renal artery, renal vein, and ureter of the donor kidney are connected to the corresponding structure in the recipient. The patient is then placed on immunosuppressive drugs to prevent rejection of the transplanted kidney. Principles of Human Anatomy and Physiology, 11e 13 Blood & Nerve Supply of Kidney • Abundantly supplied with blood vessels – receive 25% of resting cardiac output via renal arteries • Functions of different capillary beds – glomerular capillaries where filtration of blood occurs • vasoconstriction & vasodilation of afferent & efferent arterioles produce large changes in renal filtration – peritubular capillaries that carry away reabsorbed substances from filtrate – vasa recta supplies nutrients to medulla without disrupting its osmolarity form • The nerve supply to the kidney is derived from the renal plexus (sympathetic division of ANS). Sympathetic vasomotor nerves regulate blood flow & renal resistance by altering arterioles Principles of Human Anatomy and Physiology, 11e 14 Principles of Human Anatomy and Physiology, 11e 15 Nephrons • A nephron consists of a renal corpuscle where fluid is filtered, and a renal tubule into which the filtered fluid passes (Figure 26.5). • Nephrons perform three basic functions: glomerular filtration, tubular reabsorption, and tubular secretion. • A renal tubule consists of a proximal convoluted tubule (PCT), loop of Henle (nephron loop), and distal convoluted tubule (DCT). • Distal convoluted tubules of several nephrons drain into to a single collecting duct and many collecting ducts drain into a small number of papillary ducts. Principles of Human Anatomy and Physiology, 11e 16 Blood Vessels around the Nephron • Glomerular capillaries are formed between the afferent & efferent arterioles • Efferent arterioles give rise to the peritubular capillaries and vasa recta Principles of Human Anatomy and Physiology, 11e 17 Nephrons • The loop of Henle consists of a descending limb, a thin ascending limb, and a thick ascending limb (Figure 26.5). • There are two types of nephrons that have differing structure and function. – A cortical nephron usually has its glomerulus in the outer portion of the cortex and a short loop of Henle that penetrates only into the outer region of the medulla (Figure 26.5a). – A juxtamedullary nephron usually has its glomerulus deep in the cortex close to the medulla; its long loop of Henle stretches through the medulla and almost reaches the renal papilla (Figure 26.5b). Principles of Human Anatomy and Physiology, 11e 18 Blood Supply to the Nephron Principles of Human Anatomy and Physiology, 11e 19 The • Kidney has over 1 million nephrons composed of a corpuscle and tubule Nephron • Renal corpuscle = site of plasma filtration – glomerulus is capillaries where filtration occurs – glomerular (Bowman’s) capsule is doublewalled epithelial cup that collects filtrate • Renal tubule – proximal convoluted tubule – loop of Henle dips down into medulla – distal convoluted tubule • Collecting ducts and papillary ducts drain urine to the renal pelvis and ureter. Principles of Human Anatomy and Physiology, 11e 20 Cortical Nephron • 80-85% of nephrons are cortical nephrons • Renal corpuscles are in outer cortex and loops of Henle lie mainly in cortex Principles of Human Anatomy and Physiology, 11e 21 Juxtamedullary Nephron • 15-20% of nephrons are juxtamedullary nephrons • Renal corpuscles close to medulla and long loops of Henle extend into deepest medulla enabling excretion of dilute or concentrated urine Principles of Human Anatomy and Physiology, 11e 22 Histology of the Nephron and Collecting Duct • Glomerular Capsule – The glomerular capsule consists of visceral and parietal layers (Figure 26.6). – The visceral layer consists of modified simple squamous epithelial cells called podocytes. – The parietal layer consists of simple squamous epithelium and forms the outer wall of the capsule. • Fluid filtered from the glomerular capillaries enters the capsular space, the space between the two layers of the glomerular capsule. Principles of Human Anatomy and Physiology, 11e 23 Histology of the Nephron & Collecting Duct • Single layer of epithelial cells forms walls of entire tube • Distinctive features due to function of each region – microvilli – cuboidal versus simple – hormone receptors Principles of Human Anatomy and Physiology, 11e 24 Renal Tubule and Collecting Duct • Table 26.1 illustrates the histology of the cells that form the renal tubule and collecting duct. • The juxtaglomerular apparatus (JGA) consists of the juxtaglomerular cells of an afferent arteriole and the macula densa. The JGA helps regulate blood pressure and the rate of blood filtration by the kidneys (Figure 26.6). • Most of the cells of the distal convoluted tubule are principal cells that have receptors for ADH and aldosterone. A smaller number are intercalated cells which play a role in the homeostasis of blood pH. • The number of nephrons is constant from birth. They may increase in size, but not in number (Clinical Application). Principles of Human Anatomy and Physiology, 11e 25 Structure of Renal Corpuscle • Bowman’s capsule surrounds capsular space – podocytes cover capillaries to form visceral layer – simple squamous cells form parietal layer of capsule • Glomerular capillaries arise from afferent arteriole & form a ball before emptying into efferent arteriole Principles of Human Anatomy and Physiology, 11e 26 Histology of Renal Tubule & Collecting Duct • Proximal convoluted tubule – simple cuboidal with brush border of microvilli that increase surface area • Descending limb of loop of Henle – simple squamous • Ascending limb of loop of Henle – simple cuboidal to low columnar – forms juxtaglomerular apparatus where makes contact with afferent arteriole • macula densa is special part of ascending limb • Distal convoluted & collecting ducts – simple cuboidal composed of principal & intercalated cells which have microvilli Principles of Human Anatomy and Physiology, 11e 27 Juxtaglomerular Apparatus • Structure where afferent arteriole makes contact with ascending limb of loop of Henle – macula densa is thickened part of ascending limb – juxtaglomerular cells are modified muscle cells in arteriole Principles of Human Anatomy and Physiology, 11e 28 Number of Nephrons • Remains constant from birth – any increase in size of kidney is size increase of individual nephrons • If injured, no replacement occurs • Dysfunction is not evident until function declines by 25% of normal (other nephrons handle the extra work) • Removal of one kidney causes enlargement of the remaining until it can filter at 80% of normal rate of 2 kidneys Principles of Human Anatomy and Physiology, 11e 29 OVERVIEW OF RENAL PHYSIOLOGY • Nephrons and collecting ducts perform three basic processes while producing urine: glomerular filtration, tubular secretion, and tubular reabsorption (Figure 26.7). Principles of Human Anatomy and Physiology, 11e 30 Overview of Renal Physiology • Nephrons and collecting ducts perform 3 basic processes – glomerular filtration • a portion of the blood plasma is filtered into the kidney – tubular reabsorption • water & useful substances are reabsorbed into the blood – tubular secretion • wastes are removed from the blood & secreted into urine • Rate of excretion of any substance is its rate of filtration, plus its rate of secretion, minus its rate of reabsorption Principles of Human Anatomy and Physiology, 11e 31 Overview of Renal Physiology • Glomerular filtration of plasma • Tubular reabsorption • Tubular secretion Principles of Human Anatomy and Physiology, 11e 32 GLOMERULAR FILTRATION • The fluid that enters the capsular space is termed glomerular filtrate. • The fraction of plasma in the afferent arterioles of the kidneys that becomes filtrate is termed the filtration fraction. Principles of Human Anatomy and Physiology, 11e 33 Glomerular Filtration • Blood pressure produces glomerular filtrate • Filtration fraction is 20% of plasma • 48 Gallons/day filtrate reabsorbed to 1-2 qt. urine • Filtering capacity enhanced by: – thinness of membrane & large surface area of glomerular capillaries – glomerular capillary BP is high due to small size of efferent arteriole Principles of Human Anatomy and Physiology, 11e 34 The Filtration Membrane • The filtering unit of a nephron is the endothelial-capsular membrane. – glomerular endothelium – glomerular basement membrane – slit membranes between pedicels of podocytes. • Filtered substances move from the blood stream through three barriers: a glomerular endothelial cell, the basal lamina, and a filtration slit formed by a podocyte (Figure 26.8). • The principle of filtration - to force fluids and solutes through a membrane by pressure - is the same in glomerular capillaries as in capillaries elsewhere in the body. Principles of Human Anatomy and Physiology, 11e 35 Filtration Membrane • #1 Stops all cells and platelets • #2 Stops large plasma proteins • #3 Stops medium-sized proteins, not small ones Principles of Human Anatomy and Physiology, 11e 36 Net Filtration Pressure • NFP = total pressure that promotes filtration • NFP = GBHP - (CHP + BCOP) = 10mm Hg Principles of Human Anatomy and Physiology, 11e 37 Net Filtration Pressure • Glomerular filtration depends on three main pressures, one that promotes and two that oppose filtration (Figure 26.9). • Filtration of blood is promoted by glomerular blood hydrostatic pressure (BGHP) and opposed by capsular hydrostatic pressure (CHP) and blood colloid osmotic pressure (BCOP). – The net filtration pressure (NFP) is about 10 mm Hg. • In some kidney diseases, damaged glomerular capillaries become so permeable that plasma proteins enter the filtrate, causing an increase in NFP and GFR and a decrease in BCOP. (Clinical Application) Principles of Human Anatomy and Physiology, 11e 38 Glomerular Filtration Rate • Amount of filtrate formed in all renal corpuscles of both kidneys / minute – average adult male rate is 125 mL/min • Homeostasis requires GFR that is constant – too high & useful substances are lost due to the speed of fluid passage through nephron – too low and sufficient waste products may not be removed from the body • Changes in net filtration pressure affects GFR – filtration stops if GBHP drops to 45mm Hg – functions normally with mean arterial pressures 80-180 Principles of Human Anatomy and Physiology, 11e 39 Regulation of GFR • The mechanisms that regulate GFR adjust blood flow into and out of the glomerulus and alter the glomerular capillary surface area available for filtration. • The three principal mechanisms that control GFR are renal autoregulation, neural regulation, and hormonal regulation. Principles of Human Anatomy and Physiology, 11e 40 Regulation of GFR Principles of Human Anatomy and Physiology, 11e 41 Renal Autoregulation of GFR • Mechanisms that maintain a constant GFR despite changes in arterial BP – myogenic mechanism • systemic increases in BP, stretch the afferent arteriole • smooth muscle contraction reduces the diameter of the arteriole returning the GFR to its previous level in seconds – tubuloglomerular feedback • elevated systemic BP raises the GFR so that fluid flows too rapidly through the renal tubule & Na+, Cland water are not reabsorbed • macula densa detects that difference & releases a vasoconstrictor from the juxtaglomerular apparatus • afferent arterioles constrict & reduce GFR Principles of Human Anatomy and Physiology, 11e 42 Neural Regulation of GFR • Blood vessels of the kidney are supplied by sympathetic fibers that cause vasoconstriction of afferent arterioles • At rest, renal BV are maximally dilated because sympathetic activity is minimal – renal autoregulation prevails • With moderate sympathetic stimulation, both afferent & efferent arterioles constrict equally – decreasing GFR equally • With extreme sympathetic stimulation (exercise or hemorrhage), vasoconstriction of afferent arterioles reduces GFR – lowers urine output & permits blood flow to other tissues Principles of Human Anatomy and Physiology, 11e 43 Hormonal Regulation of GFR • Atrial natriuretic peptide (ANP) increases GFR – stretching of the atria that occurs with an increase in blood volume causes hormonal release • relaxes glomerular mesangial cells increasing capillary surface area and increasing GFR • Angiotensin II reduces GFR – potent vasoconstrictor that narrows both afferent & efferent arterioles reducing GFR Principles of Human Anatomy and Physiology, 11e 44 TUBULAR REABSORPTION AND TUBULAR SECRETION Principles of Human Anatomy and Physiology, 11e 45 Tubular Reabsorption & Secretion • Normal GFR is so high that volume of filtrate in capsular space in half an hour is greater than the total plasma volume • Nephron must reabsorb 99% of the filtrate – PCT with their microvilli do most of work with rest of nephron doing just the fine-tuning • solutes reabsorbed by active & passive processes • water follows by osmosis • small proteins by pinocytosis • Important function of nephron is tubular secretion – transfer of materials from blood into tubular fluid • helps control blood pH because of secretion of H+ • helps eliminate certain substances (NH4+, creatinine, K+) • Table 26.3 compares the amounts of substances that are filtered, reabsorbed, and excreted in urine with the amounts present in blood plasma. Principles of Human Anatomy and Physiology, 11e 46 Reabsorption Routes • A substance being reabsorbed can move between adjacent tubule cells or through an individual tubule cell before entering a peritubular capillary (Figure 26.11). • Fluid leakage between cells is known as paracellular reabsorption. • In transcellular reabsorption, a substance passes from the fluid in the tubule lumen through the apical membrane of a tubule cell, across the cytosol, and out into interstitial fluid through the basolateral membrane. Principles of Human Anatomy and Physiology, 11e 47 Reabsorption Routes • Paracellular reabsorption – 50% of reabsorbed material moves between cells by diffusion in some parts of tubule • Transcellular reabsorption – material moves through both the apical and basal membranes of the tubule cell by active transport Principles of Human Anatomy and Physiology, 11e 48 Transport Mechanisms • Solute reabsorption drives water reabsorption. The mechanisms that accomplish Na+ reabsorption in each portion of the renal tubule and collecting duct recover not only filtered Na+ but also other electrolytes, nutrients, and water. Principles of Human Anatomy and Physiology, 11e 49 Transport Mechanisms • Apical and basolateral membranes of tubule cells have different types of transport proteins • Reabsorption of Na+ is important – several transport systems exist to reabsorb Na+ – Na+/K+ ATPase pumps sodium from tubule cell cytosol through the basolateral membrane only • Water is only reabsorbed by osmosis – obligatory water reabsorption occurs when water is “obliged” to follow the solutes being reabsorbed – facultative water reabsorption occurs in collecting duct under the control of antidiuretic hormone Principles of Human Anatomy and Physiology, 11e 50 Active and Passive Transport Processes • Transport across membranes can be either active or passive (See Chapter 3). • In primary active transport the energy derived from ATP is used to “pump” a substance across a membrane. • In secondary active transport the energy stored in an ion’s electrochemical gradient drives another substance across the membrane. Principles of Human Anatomy and Physiology, 11e 51 Transport Maximum (Tm) • Each type of symporter has an upper limit on how fast it can work, called the transport maximum (Tm). • The mechanism for water reabsorption by the renal tubule and collecting duct is osmosis. • About 90% of the filtered water reabsorbed by the kidneys occurs together with the reabsorption of solutes such as Na+, Cl-, and glucose. • Water reabsorption together with solutes in tubular fluid is called obligatory water reabsorption. • Reabsorption of the final water, facultative reabsorption, is based on need and occurs in the collecting ducts and is regulated by ADH. Principles of Human Anatomy and Physiology, 11e 52 Glucosuria • Renal symporters can not reabsorb glucose fast enough if blood glucose level is above 200 mg/mL – some glucose remains in the urine (glucosuria) • Common cause is diabetes mellitis because insulin activity is deficient and blood sugar is too high • Rare genetic disorder produces defect in symporter that reduces its effectiveness Principles of Human Anatomy and Physiology, 11e 53 Reabsorption and Secretion in the Proximal Convoluted Tubule Principles of Human Anatomy and Physiology, 11e 54 Reabsorption in the Proximal Convoluted Tubule • The majority of solute and water reabsorption from filtered fluid occurs in the proximal convoluted tubules and most absorptive processes involve Na+. • Proximal convoluted tubule Na+ transporters promote reabsorption of 100% of most organic solutes, such as glucose and amino acids; 80-90% of bicarbonate ions; 65% of water, Na+, and K+; 50% of Cl-; and a variable amount of Ca+2, Mg+2, and HPO4-2. • Normally, 100% of filtered glucose, amino acids, lactic acid, water-soluble vitamins, and other nutrients are reabsorbed in the first half of the PCT by Na+ symporters. Figure 26.12 shows the operation of the main Na+-glucose symporters in PCT cells. Principles of Human Anatomy and Physiology, 11e 55 Reabsorption in the Proximal Convoluted Tubule • Na+/H+ antiporters achieve Na+ reabsorption and return filtered HCO3- and water to the peritubular capillaries (Figure 26.13). PCT cells continually produce the H+ needed to keep the antiporters running by combining CO2 with water to produce H2CO3 which dissociates into H+ and HCO3-. • Diffusion of Cl- into interstitial fluid via the paracellular route leaves tubular fluid more positive than interstitial fluid. This electrical potential difference promotes passive paracellular reabsorption of Na+, K+, Ca+2, and Mg+2 (Figure 26.14). • Reabsorption of Na+ and other solutes creates an osmotic gradient that promotes reabsorption of water by osmosis (Figure 26.15). Principles of Human Anatomy and Physiology, 11e 56 Reabsorption in the PCT • Na+ symporters help reabsorb materials from the tubular filtrate • Glucose, amino acids, lactic acid, water-soluble vitamins and other nutrients are completely reabsorbed in the first half of the proximal convoluted tubule • Intracellular sodium levels are kept low due to Na+/K+ pump Reabsorption of Nutrients Principles of Human Anatomy and Physiology, 11e 57 Reabsorption of Bicarbonate, Na+ & H+ Ions • Na+ antiporters reabsorb Na+ and secrete H+ – PCT cells produce the H+ & release bicarbonate ion to the peritubular capillaries – important buffering system • For every H+ secreted into the tubular fluid, one filtered bicarbonate eventually returns to the blood Principles of Human Anatomy and Physiology, 11e 58 Secretion of NH3 and NH4+ in the Proximal Convoluted Tubule • Urea and ammonia in the blood are both filtered at the glomerulus and secreted by the proximal convoluted tubule cells into the tubules. • The deamination of the amino acid glutamine by PCT cells generates both NH3 and new HCO3- (Figure 26.16). • At the pH inside tubule cells, most NH3 quickly binds to H+ and becomes NH4+. • NH4+ can substitute for H+ aboard Na+/H+ antiporters and be secreted into tubular fluid. • Na+/HCO3+ symporters provide a route for reabsorbed Na+ and newly formed HCO3- to enter the bloodstream. Principles of Human Anatomy and Physiology, 11e 59 Passive Reabsorption in the 2nd Half of PCT • Electrochemical gradients produced by symporters & antiporters causes passive reabsorption of other solutes • Cl-, K+, Ca+2, Mg+2 and urea passively diffuse into the peritubular capillaries • Promotes osmosis in PCT (especially permeable due to aquaporin-1 channels Principles of Human Anatomy and Physiology, 11e 60 Reabsorption in the Loop of Henle • The loop of Henle sets the stage for independent regulation of both the volume and osmolarity of body fluids. • Na+-K+-Cl- symporters reclaim Na+, Cl-, and K+ ions from the tubular lumen fluid (Figure 26.15). • Because K+ leakage channels return much of the K+ back into tubular fluid, the main effect of the Na+-K+-Clsymporters is reabsorption of Na+ and Cl-. • Although about 15% of the filtered water is reabsorbed in the descending limb, little or no water is reabsorbed in the ascending limb. Principles of Human Anatomy and Physiology, 11e 61 Symporters in the Loop of Henle • Thick limb of loop of Henle has Na+ K- Cl- symporters that reabsorb these ions • K+ leaks through K+ channels back into the tubular fluid leaving the interstitial fluid and blood with a negative charge • Cations passively move to the vasa recta Principles of Human Anatomy and Physiology, 11e 62 Reabsorption in the DCT • As fluid flows along the DCT, reabsorption of Na+ and Clcontinues due to Na+-Cl- symporters. – Na+ and Cl- then reabsorbed into peritubular capillaries • The DCT serves as the major site where parathyroid hormone stimulates reabsorption of Ca+2. • DCT is not very permeable to water so the solutes are reabsorbed with little accompanying water. Principles of Human Anatomy and Physiology, 11e 63 Reabsorption and Secretion in the Collecting Duct • By end of DCT, 95% of solutes & water have been reabsorbed and returned to the bloodstream • Cells in the collecting duct make the final adjustments – principal cells reabsorb Na+ • Na+ passes through the apical membrane of principal cells via Na+ leakage channels. Sodium pumps actively transport Na+ across the basolateral membrane (Figure 26.16). – Principal cells secrete a variable amount of K+ (Figure 26.16). • The secretion of K+ through K+ leakage channels in the principal cells is the main source of K+ that is excreted in urine. • intercalated cells reabsorb K+ & bicarbonate ions and secrete H+ Principles of Human Anatomy and Physiology, 11e 64 Actions of the Principal Cells • Na+ enters principal cells through leakage channels • Na+ pumps keep the concentration of Na+ in the cytosol low • Cells secrete variable amounts of K+, to adjust for dietary changes in K+ intake – down concentration gradient due to Na+/K+ pump • Aldosterone increases Na+ and water reabsorption & K+ secretion by principal cells by stimulating the synthesis of new pumps and channels. Principles of Human Anatomy and Physiology, 11e 65 Secretion of H+ and Absorption of Bicarbonate by Intercalated Cells • Proton pumps (H+ATPases) secrete H+ into tubular fluid – can secrete against a concentration gradient so urine can be 1000 times more acidic than blood • Cl-/HCO3- antiporters move bicarbonate ions into the blood – intercalated cells help regulate pH of body fluids • Urine is buffered by HPO4 2- and ammonia, both of which combine irreversibly with H+ and are excreted Principles of Human Anatomy and Physiology, 11e 66 Hormonal Regulation • Hormones that affect Na+, Cl- & water reabsorption and K+ secretion in the tubules – angiotensin II and aldosterone • decreases GFR by vasoconstricting afferent arteriole • enhances absorption of Na+ • promotes aldosterone production which causes principal cells to reabsorb more Na+ and Cl- and less water • increases blood volume by increasing water reabsorption – atrial natriuretic peptide • inhibits reabsorption of Na+ and water in PCT & suppresses secretion of aldosterone & ADH • increase excretion of Na+ which increases urine output and decreases blood volume • Table 26.4 summarizes the hormonal regulation of tubular reabsorption and tubular secretion. Principles of Human Anatomy and Physiology, 11e 67 Antidiuretic Hormone • Increases water permeability of principal cells so regulates facultative water reabsorption • Stimulates the insertion of aquaporin-2 channels into the membrane – water molecules move more rapidly • When osmolarity of plasma & interstitial fluid decreases, more ADH is secreted and facultative water reabsorption increases. Principles of Human Anatomy and Physiology, 11e 68 PRODUCTION OF DILUTE AND CONCENTRATED URINE • The rate at which water is lost from the body depends mainly on ADH, which controls water permeability of principal cells in the collecting duct (and in the last portion of the distal convoluted tubule). • When ADH level is very low, the kidneys produce dilute urine and excrete excess water; in other words, renal tubules absorb more solutes than water (Figure 26.18). Principles of Human Anatomy and Physiology, 11e 69 Formation of Concentrated Urine • Compensation for low water intake or heavy perspiration • When ADH level is high, the kidneys secrete concentrated urine and conserve water; a large volume of water is reabsorbed from the tubular fluid into interstitial fluid, and the solute concentration of urine is high. • Production of concentrated urine involves ascending limb cells of the loop of Henle establishing the osmotic gradient in the renal medulla, collecting ducts reabsorbing more water and urea, and urea recycling causing a build up of urea in the renal medulla (Figure 26.19). • The countercurrent mechanism also contributes to the excretion of concentrated urine. Principles of Human Anatomy and Physiology, 11e 70 Formation of Concentrated Urine • Urine can be up to 4 times greater osmolarity than plasma • It is possible for principal cells & ADH to remove water from urine to that extent, if interstitial fluid surrounding the loop of Henle has high osmolarity – Long loop juxtamedullary nephrons make that possible – Na+/K+/Cl- symporters reabsorb Na+ and Cl- from tubular fluid to create osmotic gradient in the renal medulla • Cells in the collecting ducts reabsorb more water & urea when ADH is increased • Urea recycling causes a buildup of urea in the renal medulla • Figure 26.20 summarizes the processes of filtration, reabsorption, and secretion in each segment of the nephron and collecting ducts. Hormonal effects are also noted. Principles of Human Anatomy and Physiology, 11e 71 Summary • H2O Reabsorption – PCT---65% – loop---15% – DCT----1015% – collecting duct--5-10% with ADH Principles of Human Anatomy and Physiology, 11e 72 Formation of Dilute Urine • Dilute = having fewer solutes than plasma (300 mOsm/liter). – diabetes insipidus • Filtrate and blood have equal osmolarity in PCT • Water reabsorbed in thin limb, but ions reabsorbed in thick limb of loop of Henle create a filtrate more dilute than plasma – can be 4x as dilute as plasma – as low as 65 mOsm/liter • Principal cells do not reabsorb water if ADH is low Principles of Human Anatomy and Physiology, 11e 73 Countercurrent Mechanism • Descending limb is very permeable to water – higher osmolarity of interstitial fluid outside the descending limb causes water to mover out of the tubule by osmosis • at hairpin turn, osmolarity can reach 1200 mOsm/liter • Ascending limb is impermeable to water, but symporters remove Na+ and Cl- so osmolarity drops to 100 mOsm/liter, but less urine is left • Vasa recta blood flowing in opposite directions than the loop of Henle -- provides nutrients & O2 without affecting osmolarity of interstitial fluid Principles of Human Anatomy and Physiology, 11e 74 Reabsorption within Loop of Henle Principles of Human Anatomy and Physiology, 11e 75 Clinical Application • Diuretics are drugs that increase urine flow rate. They work by a variety of mechanisms. The most potent ones are the loop diuretics, such as furosemide, which inhibits the symporters in the thick ascending limb of the loop of Henle. Principles of Human Anatomy and Physiology, 11e 76 Diuretics • Substances that slow renal reabsorption of water & cause diuresis (increased urine flow rate) – caffeine which inhibits Na+ reabsorption – alcohol which inhibits secretion of ADH – prescription medicines can act on the PCT, loop of Henle or DCT Principles of Human Anatomy and Physiology, 11e 77 EVALUATION OF KIDNEY FUNCTION • An analysis of the volume and physical, chemical, and microscopic properties of urine, called urinalysis, reveals much about the state of the body. • Table 26.5 summarizes the principal physical characteristics of urine. • Table 26.6 lists several abnormal constituents of urine that may be detected as part of a urinalysis. Principles of Human Anatomy and Physiology, 11e 78 EVALUATION OF KIDNEY FUNCTION • Two blood screening tests can provide information about kidney function. – One screening test is the blood urea nitrogen (BUN), which measures the level of nitrogen in blood that is part of urea. – Another test is measurement of plasma creatinine. • Renal plasma clearance expresses how effectively the kidneys remove (clear) a substance from blood plasma. – The clearance of insulin gives the glomerular filtration rate. – The clearance of para-aminohippuric acid gives the rate of renal plasma flow. Principles of Human Anatomy and Physiology, 11e 79 Clinical Application • Dialysis is the separation of large solutes from smaller ones through use of a selectively permeable membrane. • Filtering blood through an artificial kidney machine is called hemodialysis. This procedure filters the blood of wastes and adds nutrients. • A portable method of dialysis is called continuous ambulatory peritoneal dialysis. Principles of Human Anatomy and Physiology, 11e 80 URINE STORAGE, TRANSPORTATION, AND ELIMINATION • Urine drains through papillary ducts into minor calyces, which joint to become major calyces that unite to form the renal pelvis (Figure 26.3). From the renal pelvis, urine drains into the ureters and then into the urinary bladder, and finally, out of the body by way of the urethra (Figure 26.1). Principles of Human Anatomy and Physiology, 11e 81 Ureters • Each of the two ureters connects the renal pelvis of one kidney to the urinary bladder (Figure 26.21). • The ureters transport urine from the renal pelvis to the urinary bladder, primarily by peristalsis, but hydrostatic pressure and gravity also contribute. • The ureters are retroperitoneal and consist of a mucosa, muscularis, and fibrous coat. Principles of Human Anatomy and Physiology, 11e 82 Anatomy of Ureters • • • • • • 10 to 12 in long diameter from 1-10 mm Extends from renal pelvis to bladder Retroperitoneal Enters posterior wall of bladder Physiological valve only – bladder wall compresses arterial opening as it expands during filling – flow results from peristalsis, gravity & hydrostatic pressure Principles of Human Anatomy and Physiology, 11e 83 Histology of Ureters • 3 layers in wall – mucosa is transitional epithelium & lamina propria • since organ must inflate & deflate • mucus prevents the cells from being contacted by urine – muscularis • inner longitudinal & outer circular smooth muscle layer – distal 1/3 has additional longitudinal layer • peristalsis contributes to urine flow – adventitia layer of loose connective tissue anchors in place • contains lymphatics and blood vessels to supply ureter Principles of Human Anatomy and Physiology, 11e 84 Urinary Bladder • The urinary bladder is a hollow muscular organ situated in the pelvic cavity posterior to the pubic symphysis. • Anatomy and Histology of the Urinary Bladder • In the floor of the urinary bladder is a small, smooth triangular area, the trigone. The ureters enter the urinary bladder near two posterior points in the triangle; the urethra drains the urinary bladder from the anterior point of the triangle (Figure 26.21). Principles of Human Anatomy and Physiology, 11e 85 Location of Urinary Bladder • Posterior to pubic symphysis • In females is anterior to vagina & inferior to uterus • In males lies anterior to rectum Principles of Human Anatomy and Physiology, 11e 86 Anatomy of Urinary Bladder • Hollow, distensible muscular organ with capacity of 700 - 800 mL • Trigone is smooth flat area bordered by 2 ureteral openings and one urethral opening Principles of Human Anatomy and Physiology, 11e 87 Histology of Urinary Bladder • 3 layers in wall – mucosa is transitional epithelium & lamina propria • since organ must inflate & deflate • mucus prevents the cells from being contacted by urine – muscularis (known as detrusor muscle) • 3 layers of smooth muscle – inner longitudinal, middle circular & outer longitudinal • circular smooth muscle fibers form internal urethral sphincter • circular skeletal muscle forms external urethral sphincter – adventitia layer of loose connective tissue anchors in place • superior surface has serosal layer (visceral peritoneum) Principles of Human Anatomy and Physiology, 11e 88 Micturition Reflex • Micturition or urination (voiding) • Stretch receptors signal spinal cord and brain – when volume exceeds 200-400 mL • Impulses sent to micturition center in sacral spinal cord (S2 and S3) & reflex is triggered – parasympathetic fibers cause detrusor muscle to contract, external & internal sphincter muscles to relax • Filling causes a sensation of fullness that initiates a desire to urinate before the reflex actually occurs – conscious control of external sphincter – cerebral cortex can initiate micturition or delay its occurrence for a limited period of time Principles of Human Anatomy and Physiology, 11e 89 Anatomy of the Urethra • Females – length of 1.5 in., orifice between clitoris & vagina – histology • transitional changing to nonkeratinized stratified squamous epithelium, lamina propria with elastic fibers & circular smooth muscle • Males – tube passes through prostate, UG diaphragm & penis – 3 regions of urethra • prostatic urethra, membranous urethra & spongy urethra • circular smooth muscle forms internal urethral sphincter & UG diaphragm forms external urethral sphincter Principles of Human Anatomy and Physiology, 11e 90 Anatomy of the Urethra Principles of Human Anatomy and Physiology, 11e 91 Urinary Incontinence • Lack of voluntary control over micturition – normal in 2 or 3 year olds because neurons to sphincter muscle is not developed • Stress incontinence in adults – caused by increases in abdominal pressure that result in leaking of urine from the bladder • coughing, sneezing, laughing, exercising, walking – injury to the nerves, loss of bladder flexibility, or damage to the sphincter Principles of Human Anatomy and Physiology, 11e 92 Waste Management in Other Body Systems • Buffers bind excess H+ • Blood transports wastes • Liver is site for metabolic recycling – conversion of amino acids into glucose, glucose into fatty acids or toxic into less toxic substances • The lungs excrete CO2. H2O, and heat. • Sweat glands eliminate excess heat, water, and CO2, plus small quantities of salts and urea. • The GI tract eliminates solid, undigested foods, waste, some CO2, H2O, salts and heat. Principles of Human Anatomy and Physiology, 11e 93 DEVELOPMENT OF THE URINARY TRACT • The kidneys develop from intermediate mesoderm. • They develop in the following sequence: pronephros, mesonephros, and metanephros (Figure 26.22). Principles of Human Anatomy and Physiology, 11e 94 Developmental Anatomy • Mesoderm along the posterior aspect attempts to differentiate 3 times into the kidneys • Pronephros, mesonephros and metanephros Principles of Human Anatomy and Physiology, 11e 95 Later Developmental Anatomy • By 5th week, the uteric bud forms the duct system • Metanephric mesoderm forms the nephrons • Urogenital sinus forms the bladder and urethra Principles of Human Anatomy and Physiology, 11e 96 Aging and the Urinary System • After age 40, the effectiveness of kidney function begins to decrease. • Anatomical changes – kidneys shrink in size from 260 g to 200 g • Functional changes – lowered blood flow & filter less blood (50%) – diminished sensation of thirst increases susceptibility to dehydration • Diseases common with age – acute and chronic inflammations & canaliculi – infections, nocturia, polyuria, dysuria, retention or incontinence and hematuria • Cancer of prostate is common in elderly men Principles of Human Anatomy and Physiology, 11e 97 Disorders of Urinary System • • • • • Renal calculi Urinary tract infections Glomerular disease Renal failure Polycystic kidney disease Principles of Human Anatomy and Physiology, 11e 98 DISORDERS: HOMEOSTATIC IMBALANCES • Crystals of salts present in urine can precipitate and solidify into renal calculi or kidney stones. They may block the ureter and can sometimes be removed by shock wave lithotripsy. • The term urinary tract infection (UTI) is used to describe either an infection of a part of the urinary system or the presence of large numbers of microbes in urine. UTIs include urethritis (inflammation of the urethra), cystitis (inflammation of the urinary bladder), pyelonephritis (inflammation of the kidneys), and pyelitis (inflammation of the renal pelvis and its calyces). Principles of Human Anatomy and Physiology, 11e 99 Glomerular Diseases • Glomerulonephritis (Bright’s disease) is an inflammation of the glomeruli of the kidney. One of the most common causes is an allergic reaction to the toxins given off by steptococcal bacteria that have recently infected another part of the body, especially the throat. The glomeruli may be permanently damaged, leading to acute or chronic renal failure. Principles of Human Anatomy and Physiology, 11e 100 Glomerular Diseases • Chronic renal failure refers to a progressive and generally irreversible decline in glomerular filtration rate that may result from chronic glomerulonephritis, pyelonephritis, polycystic disease, or traumatic loss of kidney tissue. Principles of Human Anatomy and Physiology, 11e 101 Glomerular Diseases • Polycystic kidney disease is one of the most common inherited disorders. In infants it results in death at birth or shortly thereafter. In adults, it accounts for 6-12% of kidney transplantations. In this disorder, the kidney tubules become riddled with hundreds or thousands of cysts, and inappropriate apoptosis of cells in noncystic tubules leads to progressive impairment of renal function and eventually to renal failure. Principles of Human Anatomy and Physiology, 11e 102 end Principles of Human Anatomy and Physiology, 11e 103