Lecture 5 - Urinary System PDF

Because learning changes everything. ® Chapter 26 Urinary System Seeley’s ANATOMY & PHYSIOLOGY Thirteenth Edition Cinnamon VanPutte, Jennifer Regan, Andrew Russo © 2023 McGraw Hill, LLC. All rights re...

Because learning changes everything. ® Chapter 26 Urinary System Seeley’s ANATOMY & PHYSIOLOGY Thirteenth Edition Cinnamon VanPutte, Jennifer Regan, Andrew Russo © 2023 McGraw Hill, LLC. All rights reserved. Authorized only for instructor use in the classroom. No reproduction or further distribution permitted without the prior written consent of McGraw Hill, LLC.  Lecture Outline The kidneys employ a complex series of processes to filter our blood of toxins and to conserve water. Access the text alternative for slide images. © McGraw Hill, LLC 2  26.1 Functions of the Urinary System Urinary system is major excretory system of the body. Two kidneys produce excretory products, carried by ureters to urinary bladder which is emptied via urethra. The kidneys filter a large volume of blood to remove wastes that form urine. Urine consists of excess water, excess ions, metabolic wastes (including urea, a protein by-product), and toxic substances. The kidneys also serve other metabolic activities. © McGraw Hill, LLC 3  Functions of the Kidneys Excretion of waste products from the blood; 21% of cardiac output is filtered per minute. Regulation of blood volume and pressure by controlling extracellular fluid volume. Regulation of blood solute concentrations of the major ions, such as Na+ , Cl− , K + , Ca2+ , HCO3- , and HPO 2- 4 , as well as urea. Regulation of extracellular fluid pH by secreting H+. Regulation of red blood cell synthesis by secreting erythropoietin. Regulation of vitamin D synthesis to help regulate blood Ca2 + levels. © McGraw Hill, LLC 4  Urinary System Access the text alternative for slide images. © McGraw Hill, LLC 5  Anatomy of the Urinary System Access the text alternative for slide images. © McGraw Hill, LLC 6  Internal Anatomy and Histology of the Kidneys Cortex: outer area. Renal columns: part of cortical tissue that extends into medulla. Medulla: inner area; surrounds renal sinus. Renal pyramids: cone-shaped. Base projects into the cortex as medullary rays. Apex of pyramid is renal papilla, points toward sinus. Calyces. Minor calyx: papillae extend into funnel of minor calyx. Major calyx: converge to form renal pelvis. Renal pelvis: enlarged chamber formed by major calyces. Ureter: exits at the hilum; connects to urinary bladder. © McGraw Hill, LLC 7  Frontal Section of the Kidney and Urine Flow 1 Access the text alternative for slide images. © McGraw Hill, LLC 8  Frontal Section of the Kidney and Urine Flow 3 Access the text alternative for slide images. © McGraw Hill, LLC 9  Structure of a Nephron Nephron: functional and histological unit of the kidney. Regions of the nephron: 1. Renal corpuscle. 2. Proximal convoluted tubule. 3. Nephron Loop (Loop of Henle). 4. Distal convoluted tubule. Path of urine produced by nephron: distal convoluted tubule → collecting duct → toward renal papilla → papillary duct → minor calyx and beyond. © McGraw Hill, LLC 10  Types of Nephrons Juxtamedullary nephrons. Renal corpuscle near the cortical medullary border. Nephron loops extend deep into the medulla. (15% of nephrons) Cortical nephrons. Renal corpuscle nearer to the periphery of the cortex. Nephron loops do not extend deep into the medulla. The filtration part of a nephron is called a renal corpuscle. © McGraw Hill, LLC 11  Functional Unit of the Kidney – the Nephron Access the text alternative for slide images. © McGraw Hill, LLC 12  The Renal Corpuscle Glomerular (Bowman) capsule: outer parietal (simple squamous epithelium) and visceral (cells called podocytes) layers. (a) The renal corpuscle consists of the Glomerulus: network glomerular capsule and the glomerulus. of capillaries. Blood The glomerular capsule is indented to form a double-walled chamber and surrounds enters through afferent the glomerulus, a network of capillaries. arteriole, exits through Blood flows from the afferent arteriole into efferent arteriole. the glomerulus and leaves the glomerulus through the efferent arteriole. Access the text alternative for slide images. © McGraw Hill, LLC 13  Glomerular Capsule Parietal layer: outer. Simple squamous epithelium that becomes cube-shaped where Bowman’s capsule ends and proximal tubule begins. Visceral layer: inner. Specialized podocytes The visceral layer of the glomerular capsule covers the glomerular capillaries. Fluid from that wrap around the the blood enters the glomerular capsule and glomerular capillaries. passes into the proximal convoluted tubule of the nephron. The juxtaglomerular apparatus consists of cells from the wall of the afferent arteriole and the distal convoluted tubule Access the text alternative for slide images. © McGraw Hill, LLC 14  Fenestrae and Filtration Slits Fenestrae: window-like openings in the endothelial cells of the glomerular capillaries. Filtrations slits: gaps between the cell processes of the podocytes. Basement membrane sandwiched between the endothelial cells of the glomerular capillaries and the podocytes. Access the text alternative for slide images. © McGraw Hill, LLC 15  Filtration Membrane Filtration membrane: capillary endothelium, basement membrane and podocytes. First stage of urine formation occurs here when fluid from blood in capillaries moves across filtration membrane into the lumen inside Bowman capsule. Access the text alternative for slide images. © McGraw Hill, LLC 16  The Juxtaglomerular Apparatus Juxtaglomerular apparatus: specialized structure near glomerulus; site of renin production. Juxtaglomerular cells- ring of smooth muscle in the afferent arteriole where the latter enters glomerular capsule. Macula densa- Specialized tubule cells of the distal convoluted tubule. The distal convoluted tubule lies between the afferent and efferent arterioles. © McGraw Hill, LLC 17  The Renal Tubule Proximal convoluted tubule: simple cuboidal epithelium with many microvilli. Nephron Loop. Descending limb: first part similar to proximal tubule. Latter part simple squamous epithelium and thinner. Ascending limb: first part simple squamous epithelium and thin, distal part thicker and simple cuboidal. Distal convoluted tubule: shorter than proximal tubule. Simple cuboidal, but smaller cells and very few microvilli. Collecting ducts: form where many distal tubules come together. Larger in diameter, simple cuboidal epithelium. Form medullary rays and lead to tips of renal pyramids. © McGraw Hill, LLC 18  Arteries and Veins of the Kidneys 1 1. Renal arteries branch from abdominal aorta and form the segmental arteries. 2. Interlobar arteries ascend within renal columns toward cortex. 3. Arcuate arteries branch and arch over the base of the pyramids. 4. Cortical radiate arteries project into the cortex. 5. Afferent arterioles carry blood to the glomerular capillaries. Access the text alternative for slide images. © McGraw Hill, LLC 19  Arteries and Veins of the Kidneys 2 6. Glomerular capillaries are the sites of filtration. 7. Efferent arterioles exit the renal corpuscle. 8. Peritubular capillaries form a plexus around the proximal and distal tubules. 9. Vasa recta: specialized parts of peritubular capillaries that course into medulla along with nephron loops, then back toward cortex. Access the text alternative for slide images. © McGraw Hill, LLC 20  Arteries and Veins of the Kidneys 3 10. Peritubular capillaries drain into interlobular veins and lead to. 11. Arcuate veins. 12. Interlobar veins. 13. Renal veins. Access the text alternative for slide images. © McGraw Hill, LLC 21  26.3 Urine Production Nephrons serve as the major functional units as they regulate body fluid composition. Three major steps in urine formation: filtration, tubular reabsorption, and tubular secretion. © McGraw Hill, LLC 22  Steps in Urine Production 1. Filtration. Blood pressure in the glomerular capillaries forces fluid and small molecules out of the blood. The filtered fluid is now called filtrate. Filtration is nonselective and separates based only on size or charge of molecules. Filtration is comparable to emptying your “junk” drawer of everything except large, permanent items. Filtration does not remove everything in the blood. Filtration removes only those substances small enough to fit through the filtration membrane. 2. Tubular reabsorption. Cells in the renal tubules contain many transport proteins. These transport proteins move water and some filtered molecules from the filtrate back into the blood in the peritubular capillaries. This prevents them from being lost from the body as components of urine (these are the “saved” items from your junk drawer). Most of the filtered water and useful solutes have been returned to the blood by the time the filtrate has been modified to urine, whereas the remaining waste or excess substances, and a small amount of water form urine. 3. Tubular secretion. Certain tubule cells transport additional solutes from the blood into the filtrate. Some of these solutes may not have been filtered by the filtration membrane (these are some “throw away” items that had been left behind in your junk drawer). Access the text alternative for slide images. © McGraw Hill, LLC 23  Filtration 1 Movement of fluid, derived from blood flowing through the glomerulus, across filtration membrane. Filtrate: water, small molecules, ions that can pass through membrane. Pressure difference forces filtrate across filtration membrane. Renal fraction: part of total cardiac output that passes through the kidneys. Varies from 12 to 30%; averages 21%. Renal blood flow rate: rate of whole blood flow through kidneys. Renal blood flow rate = cardiac output × renal fraction; average value 1176 mL/min Renal plasma flow rate: renal blood flow rate × fraction of blood that is plasma: 650 mL/min. © McGraw Hill, LLC 24  Filtration 2 Glomerular filtration rate (GFR): amount of filtrate produced each minute. 180 L/day. GFR = renal plasma flow rate × filtration fraction Filtration fraction: part of plasma that is filtered into lumen of glomerular capsules; average 19%. Average urine production/day: 1 to 2 L. Most of filtrate must be reabsorbed. © McGraw Hill, LLC 25  Filtration Membrane Filtration membrane: filtration barrier. It prevents blood cells and proteins from entering lumen of the glomerular capsule, but is many times more permeable than a typical capillary. Components: 1. Fenestrated glomerular capillaries. 2. Basement membrane. 3. Podocytes of visceral layer of the glomerular capsule. Some albumin and small protein hormones enter the filtrate, but these are reabsorbed and metabolized by the cells of the proximal convoluted tubule. Very little protein normally found in urine. © McGraw Hill, LLC 26  Filtration Pressure 1 Filtration pressure: pressure gradient responsible for filtration; forces fluid from glomerular capillary across membrane into lumen of the glomerular capsule. Pressures that contribute to filtration pressure: Glomerular capillary pressure (GCP): blood pressure inside capillary tends to move fluid out of capillary into Bowman’s capsule. Capsule hydrostatic pressure (CHP): pressure of filtrate already in the lumen. Blood colloid osmotic pressure (BCOP): osmotic pressure caused by proteins in blood. Favors fluid movement into the capillary from the lumen. BCOP greater at end of glomerular capillary than at beginning because of fluid leaving capillary and entering lumen. Filtration pressure (10 mm Hg) = GCP (50 mm Hg) − CHP (10 mm Hg) − BCOP (30 mm Hg). © McGraw Hill, LLC 27  Filtration Pressure 2 Colloid osmotic pressure in Bowman’s capsule normally close to zero. During diseases like glomerular nephritis, proteins enter the filtrate and filtrate exerts an osmotic pressure, increasing volume of filtrate. High glomerular capillary pressure results from. Low resistance to blood flow in afferent arterioles. Low resistance to blood flow in glomerular capillaries. High resistance to blood flow in efferent arterioles: small diameter vessels. Filtrate is forced across filtration membrane; fluid moves into peritubular capillaries from interstitial fluid. Hypertension can damage glomerular capillaries. © McGraw Hill, LLC 28  Filtration Pressure 3 Glomerular capillary pressure (G CP). The G CP is essentially the blood pressure inside the glomerular capillaries. It is an outward pressure from blood pressing on the fenestrated capillary walls. The G CP forces fluid and solutes out of the blood into the glomerular capsule. This G CP is higher than that in other capillaries of the body. The higher G CP is due to the smaller diameter of the efferent arteriole compared to that of the afferent arteriole and glomerular capillaries. When the diameter of a vessel decreases, the resistance to blood flow through the vessel is greater. Thus, as the blood flows from the larger-diameter afferent arteriole through the glomerular capillaries to the smaller-diameter efferent arteriole, the blood pressure increases in the glomerular capillaries. Consequently, filtrate is forced across the filtration membrane into the lumen of the glomerular capsule. The G CP is approximately 50 mm Hg compared with approximately 30 mm Hg at the arterial end of other capillary networks. Access the text alternative for slide images. © McGraw Hill, LLC 29  Filtration Pressure 4 2. Capsular hydrostatic pressure (CHP). The C H P is an inward pressure that opposes filtration. C H P is due to pressure from the filtrate fluid in the capsular space. The CH P is about 10 mm Hg. 3. Blood colloid osmotic pressure (BC O P). The B C OP is also an inward pressure that opposes filtration. It is due to the osmotic pressure of plasma proteins in the glomerular capillaries. Through osmosis, these proteins draw fluid back into the glomerular capillary from the glomerular capsule. The BCOP is greater at the end of the glomerular capillary than at its beginning because there is a higher protein concentration at the end of the glomerulus. The average BCOP is approximately 30 mm Hg. 4. To calculate filtration pressure, all three filtration pressures are summed. In a normal kidney GCP is greater than the combination of CHP and BCOP. The filtration pressure is a net outward pressure of approximately 10 mm Hg. Access the text alternative for slide images. © McGraw Hill, LLC 30  Regulation of Glomerular Filtration Rate 1 Intrinsic mechanisms: autoregulation. Involves changes in degree of constriction in afferent arterioles. Myogenic mechanism: as systemic BP increases, afferent arterioles constrict and prevent increase in renal blood flow. Tubuloglomerular feedback: increased rate of blood flow of filtrate past cells of macula densa, signal sent to juxtaglomerular cells, afferent arteriole constricts. © McGraw Hill, LLC 31  Regulation of Glomerular Filtration Rate 2 Extrinsic mechanisms: sympathetic nervous system and hormones. Occurs during severe conditions such as hemorrhage or dehydration. Sympathetic simulation constricts small arteries and afferent arterioles, decreasing renal blood flow and filtrate formation. Renin secreted from juxtaglomerular cells; results in formation of angiotensin II which stimulates vasoconstriction and maintains GFR. © McGraw Hill, LLC 32  Reabsorption of Solutes In the Proximal Convoluted Tubule 1 Access the text alternative for slide images. © McGraw Hill, LLC 33  Reabsorption in the Nephron Loop: The Descending Limb and the Thin Segment of the Ascending Limb 1 1. The epithelial tissue in the majority of the descending limb, in particular the thin segment, is simple squamous epithelial tissue. Remember from chapter 4 that simple squamous cells are highly permeable to water, which means the descending limb is highly permeable to water. In addition, the descending limb is moderately permeable to ions such as Na+ and Cl- , as well as molecules such as urea. Water moves by osmosis out of the descending limb, while some solutes move by diffusion into the descending limb. The particular factors determining the direction of water and solute movement in the descending limb will be discussed later in this section. Ultimately, by the time the filtrate has reached the end of the thin segment, the volume of the filtrate has been reduced by another 15% and its concentration has significantly increased to 1200 mOsm/L. Access the text alternative for slide images. © McGraw Hill, LLC 34  Reabsorption in the Nephron Loop: The Descending Limb and the Thin Segment of the Ascending Limb 2 2. As the nephron loop makes its hairpin turn into the ascending limb, the simple squamous epithelium persists, but it has become impermeable to water. However, it is still permeable to solutes, which exit the ascending limb, thereby again reducing the concentration of the filtrate. As the ascending limb continues, the epithelial tissue transitions to become simple cuboidal. This portion of the ascending limb is now called the thick segment. The thick segment of the ascending limb is impermeable to both water and solutes. Instead, the cells of the thick segment house multiple types of transport proteins including ATP-powered pumps and symporters. These transport proteins remove a significant portion of the solutes from the filtrate, which then enters the interstitial fluid. It is this active transport of solutes that contributes to the kidneys’ ability to conserve water. Access the text alternative for slide images. © McGraw Hill, LLC 35  Reabsorption In the Thick Segment of the Ascending Limb of the Nephron Loop 1 Access the text alternative for slide images. © McGraw Hill, LLC 36  Secretion of Hydrogen and Potassium Into the Renal Tubule (a) Hydrogen ions are secreted into the filtrate by an antiport mechanism in the proximal convoluted tubule, in which H+ are exchanged for Na+. The H+ are derived from two sources. They diffuse from the peritubular capillaries into the interstitial fluid and then into epithelial cells of the tubule, or they are derived from the reaction between carbon dioxide and water in the cells of the tubule. Sodium ions and HCO3- are symported across the basal membrane into the interstitial fluid and then diffuse into the peritubular capillaries. (b) Hydrogen ions and K + are secreted into the filtrate by antiport mechanisms in the distal convoluted tubule. Sodium ions and K + are moved by active transport across the basal membrane of the tubule cell. Sodium ions and HCO3- are symported across the basal membrane into the interstitial fluid and then diffuse into the peritubular capillaries. Access the text alternative for slide images. © McGraw Hill, LLC 37  Urine Concentration Mechanism Kidneys can produce urine with concentrations ranging from a minimum of 65 mOsm/kg to a maximum of 1200 mOsm/kg. Ability to control volume and concentration of urine depends on: 1. Countercurrent mechanisms. 2. Medullary concentration gradient. 3. Hormonal mechanisms. © McGraw Hill, LLC 38  Countercurrent Mechanisms Countercurrent mechanism: fluid in separate structures flows in opposite directions; materials may be exchanged as they pass. Countercurrent multiplier in the nephron loop is responsible for much of the high solute concentration in the interstitial fluid of medulla. Countercurrent exchanger in the vasa recta maintains the high solute concentration in the interstitial fluid. © McGraw Hill, LLC 39  Summary of Urine Formation 1 1. In the average person, about 180 L of filtrate enter the proximal convoluted tubules daily. 2. Glucose, amino acids, Na+ ,Ca2 + ,K + ,CI- , water, and other substances move from the lumens of the proximal convoluted tubules into the interstitial fluid. The excess solutes and water then enter the peritubular capillaries. Consequently, cells of the proximal convoluted tubule reabsorb approximately 65% of the filtrate, which moves solutes and water into the interstitial fluid. The osmolality of both the interstitial fluid and the filtrate is maintained at about 300 mOsm/kg. 3. As the filtrate continues to flow through the renal tubule, it enters the descending limbs of the nephron loops. This portion of the nephron loops is highly permeable to water and solutes. As the descending limbs penetrate deep into the kidney medulla, the surrounding interstitial fluid has a progressively greater osmolality. Water diffuses out of the nephron loops as solutes slowly diffuse into them. By the time the filtrate reaches the deepest part of the nephron loops, its volume has been reduced by an additional 15% of the original volume, at least 80% of the filtrate volume has been reabsorbed, and its osmolality has increased to about 1200 mOsm/kg. Access the text alternative for slide images. © McGraw Hill, LLC 40  Summary of Urine Formation 2 4. Both the thin and thick segments are impermeable to water, but solutes diffuse out of the thin segment, and Na+ ,Cl- , and K + are symported from the filtrate into the interstitial fluid in the thick segments. The movement of solutes, but not water, across the wall of the ascending limbs causes the osmolality of the filtrate to decrease from 1200 to about 100 mOsm/kg by the time the filtrate again reaches the kidney cortex. 5. The volume of the filtrate does not change as it passes through the ascending limbs. As a result, the filtrate entering the distal convoluted tubules is dilute, compared with the concentration of the surrounding interstitial fluid, which has an osmolality of about 300 mOsm/kg. 6. The distal convoluted tubule and collecting duct are permeable to water when under hormonal regulation. 7. Around 1% or less of the filtrate remains as urine, when the body is conserving water. Access the text alternative for slide images. © McGraw Hill, LLC 41  26.4 Regulation of Urine Concentration and Volume Filtrate reabsorption in the proximal convoluted tubules and the descending limbs of the nephron loops is obligatory and therefore remains relatively constant. However, filtrate reabsorption in the distal convoluted tubules and collecting ducts is tightly regulated and can change dramatically, depending on body conditions. Regulation of urine concentration and volume involves hormonal mechanisms as well as autoregulation and the sympathetic nervous system. Hormonal mechanisms include renin-angiotensin- aldosterone mechanism and antidiuretic hormone (ADH) mechanism. © McGraw Hill, LLC 42  Renin-Angiotensin-Aldosterone Hormone Mechanism Mechanism initiated under low blood pressure conditions; counteracts dropping blood pressure. Renin released by juxtaglomerular cells. Renin converts angiotensinogen to angiotensin I. Angiotensin-converting enzyme (ACE) in lungs converts angiotensin I to angiotensin II, a potent vasoconstrictor which also stimulates aldosterone secretion, sensation of thirst, and ADH secretion. Aldosterone acts on DCT and CD to increase sodium reabsorption and therefore water reabsorption. © McGraw Hill, LLC 43  Effect of Aldosterone on the DCT 1 1. When blood pressure decreases, cells of the juxtaglomerular apparatuses in the kidneys secrete the enzyme renin. The kidneys detect the low blood pressure when juxtaglomerular cells detect reduced stretch of the afferent arteriole. In addition, the macula densa cells signal the juxtaglomerular cells to secrete renin when the Na+ concentration of the filtrate drops. 2. Upon secretion, renin enters the blood and converts angiotensinogen, a plasma protein produced by the liver, to angiotensin I. Access the text alternative for slide images. © McGraw Hill, LLC 44  Effect of Aldosterone on the DCT 2 3. Angiotensin-converting enzyme (ACE) is a proteolytic enzyme produced by capillaries of organs such as the lungs. ACE converts angiotensin I to angiotensin II. Angiotensin II is a potent vasoconstricting hormone that increases peripheral resistance, causing blood pressure to increase. However, angiotensin II is rapidly broken down, so its effect lasts for only a short time. Angiotensin II also increases the rate of aldosterone secretion, the sensation of thirst, salt appetite, and ADH secretion. The rate of renin secretion decreases if blood pressure in the afferent arteriole increases, or if the Na+ concentration of the filtrate increases as it passes by the macula densa of the juxtaglomerular apparatuses. Access the text alternative for slide images. © McGraw Hill, LLC 45  Effect of Aldosterone on the DCT 3 4. A large decrease in the concentration of Na+ in the interstitial fluid acts directly on the aldosterone-secreting cells of the adrenal cortex to increase the rate of aldosterone secretion. However, angiotensin II is much more important than the blood level of Na+ for regulating aldosterone secretion. In addition, angiotensin II is critical for returning GFR to normal levels. Aldosterone is a steroid hormone secreted by the cortex of the adrenal glands. Aldosterone binds to its receptor in both the distal convoluted tubules and the collecting ducts. Aldosterone molecules diffuse through the plasma membranes and bind to their nuclear receptors. Access the text alternative for slide images. © McGraw Hill, LLC 46  Effect of Aldosterone on the DCT 4 6. Binding of aldosterone to its receptor increases synthesis of the Na + − K + pump and other Na + transport proteins. The Na + − K + pump increases the reabsorption of Na + and the secretion of K + across the basal membrane of tubule cells. While the other Na + transport proteins increase the transport of Na + across the apical membrane of tubule + cells. As a result, the rate of Na reabsorption increases. Simultaneously, because of the action of the Na+ − K + pump, K + secretion increases, rather than its reabsorption. Access the text alternative for slide images. © McGraw Hill, LLC 47  Antidiuretic Hormone Mechanism Antidiuretic hormone (AD H) produced by hypothalamic neurons, stored in posterior pituitary. Osmoreceptors in hypothalamus detect increased osmolality of interstitial fluid, stimulating ADH to be released. Baroreceptors in atria of heart and some vessels can also stimulate ADH release when blood pressure drops. A DH acts on DCT and CD to increase water reabsorption (by insertions of aquaporins), countering any decrease in blood pressure and/or increase in solute concentration. Insufficient A D H secretion = diabetes insipidus. © McGraw Hill, LLC 48  Effect of ADH on Renal Tubule Water Movement 1. ADH moves from the peritubular capillaries and binds to A DH receptors in the plasma membranes of the distal convoluted tubule cells and the collecting duct cells. 2. When ADH binds to its receptor, a G protein mechanism is activated, which in turn activates adenylate cyclase. 3. Adenylate cyclase increases the rate of ca MP synthesis. Cyclic A M P promotes the insertion of aquaporin-2 containing cytoplasmic vesicles into the apical membranes of the distal convoluted tubules and collecting ducts, thereby increasing their permeability to water. Water then moves by osmosis out of the distal convoluted tubules and collecting ducts into the tubule cells through the aquaporin-2 water channels. 4. Water exits the tubule cells and enters the interstitial fluid through aquaporin-3 and aquaporin-4 water channels in the basal membranes. Access the text alternative for slide images. © McGraw Hill, LLC 49  Effect of ADH on Urine Concentration and Volume (a) In the presence of ADH, the collecting duct is permeable to water and water is reabsorbed into the interstitial fluid. The result is the production of a small volume of concentrated urine. (b) In the absence of ADH, the collecting duct is impermeable to water and water remains in the collecting duct. The result is the production of a large volume of dilute urine. Access the text alternative for slide images. © McGraw Hill, LLC 50  Atrial Natriuretic Hormone Atrial natriuretic hormone (ANH) is produced by cells in right atrium of heart when they are stretched more than normal. Increases stretch due to high blood volume. ANH decreases blood volume by. Inhibiting Na + reabsorption (therefore less water reabsorbed). Inhibiting ADH production. Increases volume of urine produced. Venous return is lowered, volume in right atrium decreases. © McGraw Hill, LLC 51  Regulation of Blood Pressure (1) Blood volume is in the normal range. (2) Blood volume increases outside the normal range, which causes homeostasis to be disturbed. (3) The control centers respond to the change in blood volume. (4) The control centers cause ADH and aldosterone secretion to decrease, which reduced water reabsorption. The control centers also cause dilation of renal arteries, which increases urine production. The heart secretes ANH, which also increases urine production. (5) These changes cause blood volume to decrease. (6) Blood volume returns to the normal range and homeostasis is restored. Observe the responses to a decrease in blood volume outside the normal range by following the pink arrows. Access the text alternative for slide images. © McGraw Hill, LLC 52  26.6 Urine Movement Ureters: bring urine from renal pelvis to urinary bladder. Lined by transitional epithelium. Urinary bladder: hollow muscular container. In pelvic cavity posterior to symphysis pubis. Lined with transitional epithelium; muscle part of wall is detrusor muscle. Trigone: interior of urinary bladder. Triangular area between the entry of the two ureters and the exit of the urethra. Area expands less than rest of bladder during filling. © McGraw Hill, LLC 53  Ureters and Urinary Bladder ©Victor Eroschenko Access the text alternative for slide images. © McGraw Hill, LLC 54  Urine Flow Through the Nephron and Ureters Hydrostatic pressure forces urine through nephron. Peristalsis moves urine through ureters from region of renal pelvis to urinary bladder. Occur from once every few seconds to once every 2 to 3 minutes. Parasympathetic stimulation: increase frequency. Sympathetic stimulation: decrease frequency. Ureters enter bladder obliquely through trigone. Pressure in bladder compresses ureter and prevents backflow. © McGraw Hill, LLC 55  Micturition Reflex 1 Urinary bladder is reservoir for urine; can stretch to hold about 1 L due to folds of the wall, the transitional epithelium, and stretch of the smooth muscle. Micturition reflex is activated when urinary bladder is stretched. Detected by stretch receptors. Parasympathetic action potentials cause detrusor muscle to contract. Decreased somatic motor signals cause external urethral sphincter to relax. © McGraw Hill, LLC 56  Micturition Reflex 2 1. Urine filling the urinary bladder stimulates stretch receptors, which produce action potentials. 2. The action potentials are carried by sensory neurons to the sacral segments of the spinal cord through the pelvic nerves. 3. In response, action potentials travel to the urinary bladder through parasympathetic fibers in the pelvic nerves. The parasympathetic action potentials cause the smooth muscle of the urinary bladder (the detrusor muscle) to contract. In addition, decreased somatic motor action potentials cause the external urethral sphincter, which consists of skeletal muscle, to relax. Urine flows from the urinary bladder when the pressure there is great enough to force the urine through the urethra while the external urethral sphincter is relaxed. The micturition reflex normally produces a series of contractions of the urinary bladder. Access the text alternative for slide images. © McGraw Hill, LLC 57  Micturition Reflex 3 4. Action potentials carried by sensory neurons from stretch receptors in the urinary bladder wall also ascend the spinal cord to a micturi- tion center in the pons and to the cerebrum. 5. The micturition reflex integrated in the spinal cord is automatic, but it is either stimulated or inhibited by descending action potentials sent to the sacral region of the spinal cord. For example, higher brain centers prevent micturition by sending action potentials from the cerebrum and pons through spinal pathways to inhibit the spinal micturition reflex. Consequently, parasympathetic stimulation of the urinary bladder is inhibited, and somatic motor neurons that keep the external urethral sphincter contracted are stimulated. The micturition reflex, integrated in the spinal cord, predominates in infants. The ability to inhibit micturition voluntarily develops at the age of 2 to 3 years; subsequently, the influence of the pons and cerebrum on the spinal micturition reflex predominates. Access the text alternative for slide images. © McGraw Hill, LLC 58  Effects of Aging on the Kidneys Gradual decrease in size of kidneys, but only one-third of one kidney necessary for homeostasis. Amount of blood flowing through gradually decreases. Number of glomeruli decrease and ability to secrete and reabsorb decreases. Ability to concentrate urine declines and kidney becomes less responsive to ADH and aldosterone. Reduced ability to participate in vitamin D synthesis, contributing to Ca2+ deficiency, osteoporosis, and bone fractures. © McGraw Hill, LLC 59  Chapter 27 Fluid, Electrolyte, and Acid-Base Balance Seeley’s ANATOMY & PHYSIOLOGY Thirteenth Edition Cinnamon VanPutte, Jennifer Regan, Andrew Russo © 2023 McGraw Hill, LLC. All rights reserved. Authorized only for instructor use in the classroom. © McGraw Hill, LLC No reproduction or further distribution permitted without the prior written consent of McGraw Hill, LLC.  Lecture Outline Maintaining a homeostatic balance of electrolytes and fluids is important for proper functioning of the body. Access the text alternative for slide images. © McGraw Hill, LLC 61  Concentration of Major Solutes Primary intracellular ions, interstitial fluid ions, and plasma ions. Intracellular cation = K +. Interstitial fluid cation = Na+. + Plasma cation = Na. Intracellular anion = Protein and phosphate Interstitial fluid = Cl−. Plasma anion = Cl−. Access the text alternative for slide images. © McGraw Hill, LLC 62  Exchange Between Compartments The two major forces that determine fluid movement into and out of the blood are hydrostatic pressure and osmotic pressure. Total osmotic pressure in each compartment is approximately equal. Allows for continuous exchange of water and electrolytes. Osmosis has the greatest influence on maintaining fluid homeostasis between extracellular fluid compartments. © McGraw Hill, LLC 63  Influence of Osmotic Pressure on Fluid Movement (a) The two main forces regulation fluid movement into and out of the blood are hydrostatic pressure and osmotic pressure. (b) When osmotic pressures on each side of a plasma membrane are equal, there is no net movement of water molecules. (c) If osmotic pressure is higher in the interstitial fluid than that in the blood, there is a net movement of water by osmosis out of the blood. (d) If osmotic pressure of the blood is higher than that of the interstitial fluid, there is net movement of water by osmosis into the blood. Access the text alternative for slide images. © McGraw Hill, LLC 64  Regulation of Intracellular Fluid Very different from extracellular fluid due to: Selectively permeable plasma membrane Large molecules synthesized by the cell can not leave Transport proteins in the plasma membrane, some of which use ATP for pumps that maintain an uneven distribution of molecules and ions. Access the text alternative for slide images. © McGraw Hill, LLC 65  Regulation of Fluid Balance Thirst is the sensation that induces an urge to drink liquids. Mechanisms that control thirst are : Hypothalamic osmoreceptors Arterial and juxtaglomerular apparatus baroreceptors Dryness of the mouth Distention of the stomach © McGraw Hill, LLC 66  Effect of Blood Pressure on Thirst 1 1. Hypothalamic osmoreceptors. Neurons in the supraoptic nucleus of the hypothalamus function as osmoreceptors by detecting increases in the concentration of the extracellular fluid. When the solute concentration of the extracellular fluid increases, water moves out of these osmoreceptors by osmosis, shrinking them. When they shrink, they are triggered to send action potentials, which result in the thirst sensation. Access the text alternative for slide images. © McGraw Hill, LLC 67  Effect of Blood Pressure on Thirst 2 2. Arterial and juxtaglomerular apparatus baroreceptors. Baroreceptors are sensitive to the degree of stretch on blood vessel walls. Low blood pressure reduces the stretch on the walls of blood vessels. In response to low blood pressure, arterial baroreceptors send action potentials to the thirst center in the hypothalamus, which increases the sensation of thirst. In the kidney, the juxtaglomerular apparatus baroreceptors stimulate the juxtaglomerular cells to secrete the enzyme renin when blood pressure drops. Renin activates the steps in the formation of the hormone angiotensin II. Angiotensin II, in addition to other mechanisms that raise blood pressure, stimulates thirst. Access the text alternative for slide images. © McGraw Hill, LLC 68  Effect of Blood Pressure on Thirst 3 3. Mouth dryness. A reduction in saliva production results when the amount of water in the body decreases. The lack of saliva dries the mouth and stimulates sensory neurons in the mouth to send action potentials to the thirst center in the hypothalamus. 4. Stomach distension. Stomach distention is more influential in decreasing thirst. Too much water consumption can be just as dangerous as too little. Thus, when the total water content in the body is adequate, the thirst sensation decreases. Access the text alternative for slide images. © McGraw Hill, LLC 69  Regulation of Fluid Output Fluid output is regulated by influencing urine output as well as mechanisms that reduce thirst. Mechanisms include those that monitor blood pressure that is directly related to blood volume: Carotid sinus and aortic arch baroreceptors monitor systemic blood pressure Receptors of the juxtaglomerular apparatus monitor kidney blood pressure Receptors in the atria of the heart monitor changes in pressure through venous return These receptors activate neural and hormonal mechanisms that regulated extracellular fluid volume. © McGraw Hill, LLC 70  27.2 Electrolyte Balance Electrolytes are formed when molecules dissociate into ions in water. Inorganic salts, inorganic acids and bases, some proteins. Nonelectrolytes do not dissociate into ions in water; for example, lipids, urea, glucose. Electrolytes, especially sodium, are the component of the body’s fluids that contribute the greatest influence to their osmolality, and can be either cations or anions. The regulation of electrolytes involves the coordinated participation of several organ systems. © McGraw Hill, LLC 71  Regulation of Sodium 1 Function: Dominant extracellular cation that exerts substantial osmotic pressure (90 to 95%) Regulation: Sodium ions are dominant extracellular cations; exert substantial osmotic pressure. Kidneys are major route sodium is excreted. Aldosterone increases sodium reabsorption in kidney. Sodium levels affect blood pressure because water follows sodium. ADH stimulates both water reabsorption in the kidneys and thirst. Overall, ADH is a water conservation hormone. ANH increases Na+ and water excretion © McGraw Hill, LLC 72  Summary of Blood Potassium Regulation (1) Blood K is in the normal range. (2) Blood K increases outside the normal range, which causes homeostasis to be disturbed. (3) The control center responds to the change in blood K +. (4) The control center causes aldosterone to be secreted, which increases K + secretion at the distal convoluted tubule and the collecting duct. (5) These changes cause blood K + to decrease. + (6) Blood K returns to the normal range and homeostasis is restored. Observe the responses to a decrease in blood K + outside the normal range by following the pink arrows. Access the text alternative for slide images. © McGraw Hill, LLC 73  Regulation of Calcium Ions 1 Function: Important for exocytosis, including neurotransmitters Needed for muscle contraction Regulates action potential in cardiac muscle Regulation: Regulated by the kidneys, digestive tract, and bones. Balance between deposition and reabsorption from bone. Balance between absorption from intestines and excretion by kidneys. © McGraw Hill, LLC 74  Regulation of Calcium Ions 2 Regulation, cont. Parathyroid hormone (PTH) secreted when blood calcium levels are low. Acts to: Stimulates osteoclasts to reabsorb bone to release calcium Increases renal reabsorption of calcium Increases rate of vitamin D3 formation; needed for absorption of calcium in the intestines. Calcitonin released by thyroid gland when blood calcium levels are high. Acts to: Inhibit osteoclasts © McGraw Hill, LLC 75  Regulation of Calcium Ions 3 Imbalances: Elevated extracellular levels prevent membrane depolarization. Decreased levels lead to spontaneous action potential generation. Hypocalcemia: low calcium levels in ECF; spontaneous AP generation in nerve and muscle tissue. Hypercalcemia: high calcium levels in ECF; deposition of calcium carbonate salts in tissues, resulting in inflammation. © McGraw Hill, LLC 76  Regulation of Phosphate Ions 1 Function: Most phosphates are tied to calcium in bones Form phospholipids, DNA, RNA, and ATP Regulate enzyme activity Acts as intracellular buffers Most common form is HPO-2 4 © McGraw Hill, LLC 77  Regulation of Phosphate Ions 2 Regulation: Kidney capacity to reabsorb phosphate ions is limited. PTH raises phosphate levels through bone reabsorption. Excess phosphate is either excreted in urine or precipitate as calcium phosphate salts in soft tissues. Imbalances: Hypophosphatemia: low phosphate levels; due to reduced absorption from intestine from vitamin D deficiency or alcohol abuse. Hyperphosphatemia: high phosphate levels; due to renal failure, chemotherapy, hyperparathyroidism (secondary to elevated plasma calcium levels). © McGraw Hill, LLC 78  Regulation of Magnesium Ions 1 Function: Most magnesium stored in bones or ICF. Less than 1% in ECF; found either bound to plasma proteins or as free ions. Cofactors for intracellular enzymes, particularly with the Na + -K + pump. Regulation: Free magnesium ions pass freely through the filtration membranes of the kidneys and most are reabsorbed from the filtrate in the nephron loop. Control of reabsorption mechanism is unclear. © McGraw Hill, LLC 79  Regulation of Magnesium Ions 2 Imbalances: High and low levels of plasma magnesium produce symptoms associated with the Na + -K + pump. Hypomagnesemia: low blood levels of magnesium; weakness and muscle convulsions. Hypermagnesemia: high blood levels of magnesium; nausea, low BP, low respiratory rate. © McGraw Hill, LLC 80  27.3 Hormonal Mechanisms Regulating Body Fluid Composition Blood volume changes are directly proportional to blood pressure changes. Three hormonal mechanisms regulated this relationship: Renin-angiotensin-aldosterone hormone mechanism Atrial natriuretic hormone (ANH) mechanism Antidiuretic hormone (ADH) mechanism © McGraw Hill, LLC 81  Effect of Blood Pressure on Na+ and Water Reabsorption in the Kidneys The renin-angiotensin-aldosterone mechanism acts to increase blood pressure when it drops to low. The juxtaglomerular cells detect a drop in B P in the afferent arterioles and secrete renin which converts angiotensinogen to angiotensin 1, which converts to angiotensin II. Angiotensin II raises BP by vasoconstriction, stimulation of thirst, and release of aldosterone. Aldosterone stimulates reabsorption of Na+ and water follows by osmosis. Blood volume and pressure increase. Access the text alternative for slide images. © McGraw Hill, LLC 82  Effect of Blood Pressure in the Right Atrium of Na+ and Water Excretion In response to increased venous return to the right atrium, atrial natriuretic hormone (ANH) is released. + ANH reduces Na reabsorption in the distal convoluted tubules and collecting ducts by increasing the excretion of Na+ and water follows by osmosis. Access the text alternative for slide images. © McGraw Hill, LLC 83  Effect of Blood Osmolality and Blood Pressure on Water Reabsorption in the Kidneys Low blood pressure stimulates ADH secretion that promotes the reabsorption of water form the distal convoluted tubule and collecting ducts. This increased blood volume and therefore blood pressure. Access the text alternative for slide images. © McGraw Hill, LLC 84  Blood Osmolality Regulation (1) Blood osmolality is in the normal range. (2) Blood osmolality increases outside the normal range, which causes homeostasis to be disturbed. (3) The control center responds to the change in blood osmolality. (4) The control center causes ADH to be secreted, which increases water reabsorption at the distal convoluted tubule and the collecting duct. (5) These changes cause blood osmolality to decrease. (6) Blood osmolality returns to the normal range and homeostasis is restored. Observe the responses to a decrease in blood osmolality outside the normal range by following the pink arrow Access the text alternative for slide images. © McGraw Hill, LLC 85  27.3 Acid-Base Balance Hydrogen ions affect the activity of enzymes and interact with many electrically charged particles. Most reactions in the body are sensitive to H+ pH is the measure of hydrogen ion concentration in an inverse relationship. pH scale is from 0 to 14, with 0 being the most acidic and 14 being the least acidic (most basic) © McGraw Hill, LLC 86  Chemical Buffer Systems 1 Carbonic Acid/Bicarbonate Buffer System: A weak acid formed by CO2 reacting with water. H2CO3  HCO3- + H+ Excess H+ reacts with HCO3- to form H2CO3 - Excess base reacts with the H2CO3 to form HCO3 This system is important in controlling extracellular pH; It responds quickly to: Addition of CO2 or lactate from increased metabolism Increased fatty acid and ketone body production Addition of large amounts of basic substances such as antacids Essential part of both physiological buffer systems. © McGraw Hill, LLC 87  Chemical Buffer Systems 2 Protein Buffer System Made up of intracellular proteins and plasma proteins Hemoglobin in RBCs very important protein buffer. Can function as buffers because the carboxyl (-COOH) group and amino (-NH2) group of amino acids can act as weak acids and bases and bind to or release H+ as needed. © McGraw Hill, LLC 88  Chemical Buffer Systems 3 Phosphate Buffer System Most important intracellular buffer system. Phosphate containing molecules such as DNA, RNA, ATP, and phosphate ions act as buffers. Excess H+ reacts with HPO2- 4 → H2PO - 4 Excess OH- reacts with 2 4 H PO - → HPO 2- 4 © McGraw Hill, LLC 89  Physiological Buffer Systems Regulation of Acid-Base Balance by the Respiratory System1 Achieved through carbonic acid/bicarbonate buffer system. H2O+CO2  H2CO3  H+ + HCO3- As carbon dioxide levels increase, pH decreases; reaction pushed to the right As carbon dioxide levels decrease, pH increases; reaction pushed to the left. © McGraw Hill, LLC 90  Regulation of Acid-Base Balance by the Respiratory System 1 Carbon dioxide levels and pH affect respiratory centers. Hypoventilation increases blood carbon dioxide levels. Hyperventilation decreases blood carbon dioxide levels © McGraw Hill, LLC 91  Regulation of Acid-Base Balance by the Respiratory System 2 1. The reaction between CO2 and H2O is catalyzed by the enzyme carbonic anhydrase, which is found in a relatively high concentration in red blood cells and on the surface of capillary epithelial cells. This enzyme does not influence equilibrium but accelerates the rate at which the reaction proceeds in either direction, so that equilibrium is achieved quickly. 2. Chemoreceptors detect decreases in body fluid pH causing neurons in the respiratory center in the brainstem to increase the rate and depth of breathing. 3. This eliminates CO2 from the body through the lungs at a greater rate. The decline in CO2 levels results in the formation of H2CO3, The dissociation of H2CO3 into CO2 and H2O lowers H+ levels and pH becomes more basic. Access the text alternative for slide images. © McGraw Hill, LLC 92  Regulation of Acid-Base Balance by the Renal System Secretion of H+ into filtrate and reabsorption of HCO3- into ECF cause extracellular pH to increase. + - - HCO in filtrate reabsorbed returned to ECF by the 3 Na HCO 3 symporter in the basal membrane. Rate of H+ secretion increases as body fluid pH decreases or as aldosterone levels increase. Secretion of H+ inhibited when urine pH falls below 4.5. + Buffers in the filtrate combine with secreted H : Bicarbonate buffer. Phosphate ions. Ammonia. © McGraw Hill, LLC 93  Regulation of Body Fluid Acid-Base Balance by the Kidneys 1. Carbonic anhydrase within tubule cells catalyzes the formation of H2CO3, which dissociates into H+ and HCO −. 2. An antiport system then exchanges H+ for Na+ across the apical membrane of the cells. Thus, + tubule cells secrete H+ into the filtrate and reabsorb Na. 3. The Na+ and HCO3− are symported across the basal membrane. + − 4. After the Na and HCO3 are symported from the tubule cells, they diffuse into the peritubular capillaries. As a result, H+ is secreted into the lumens of the tubules, and HCO3− passes into the extracellular fluid. Access the text alternative for slide images. © McGraw Hill, LLC 94  Hydrogen Ion Buffering in the Filtrate Access the text alternative for slide images. © McGraw Hill, LLC 95