Chapter 23: Urinary System Learning Outcomes

Explain how the collecting duct and antidiuretic hormone regulate the volume and concentration of urine.

• The kidney eliminates metabolic wastes from the body, but prevents excessive water loss • As the kidney returns water to the tissue fluid and bloodstream, the fluid remaining in the renal tubules passes as urine, and becomes more concentrated • Collecting duct (CD) begins in the cortex where it receives tubular fluid from several nephrons • CD runs through medulla, and reabsorbs water, making urine up to four times more concentrated • Medullary portion of CD is more permeable to water than to NaCl • As urine passes through then increasingly salty medulla, water leaves by osmosis, concentrating urine • How concentrated the urine becomes depends on body's state of hydration • Water diuresis—drinking large volumes of water will produce a large volume of hypotonic urine - Cortical portion of CD reabsorbs NaCl, but it is impermeable to water - Salt is removed from the urine but water stays in - Urine concentration may be as low as 50 mOsm/L • Dehydration leads to production of hypertonic urine - Urine becomes scanty and more concentrated - High blood osmolarity stimulates posterior pituitary to release ADH and then an increase in synthesis of aquaporin channels by renal tubule cells - More water is reabsorbed by collecting duct - Urine is more concentrated • If BP is low in a dehydrated person, GFR will be low - Filtrate moves more slowly and there is more time for reabsorption - More salt removed, more water reabsorbed, and less urine produced

Explain how the kidney maintains an osmotic gradient in the renal medulla that enables the collecting duct to function.

Countercurrent Multiplier: • The ability of kidney to concentrate urine depends on salinity gradient in renal medulla • Nephron loop acts as countercurrent multiplier • Multiplier: continually recaptures salt and returns it to extracellular fluid of medulla which multiplies the osmolarity of adrenal medulla • Countercurrent : because of fluid flowing in opposite directions in adjacent tubules of nephron loop. • Fluid flowing downward in descending limb - Passes through environment of increasing osmolarity - Most of descending limb very permeable to water but not to NaCl - Water passes from tubule into the ECF leaving salt behind - Concentrates tubular fluid to 1,200 mOsm/L at lower end of loop • Fluid flowing upward in ascending limb - Impermeable to water - Reabsorbs Na+, K+, and Cl− by active transport pumps into ECF - Maintains high osmolarity of renal medulla - Tubular fluid becomes dilute: 100 mOsm/L at top of loop • Recycling of urea adds to high osmolarity of deep medulla - Lower end of collecting duct is permeable to urea but neither thick segment of loop nor DCT is permeable to urea - Urea is continually cycled from collecting duct to the nephron loop and back - Urea remains concentrated in the collecting duct and some of it always diffuses out into the medulla adding to osmolarity • Vasa recta—capillary branching off efferent arteriole in medulla - Provides blood supply to medulla and does not remove NaCl and urea from medullary ECF • Countercurrent system—formed by blood flowing in opposite directions in adjacent parallel capillaries • Descending capillaries of vasa recta - Exchanges water for salt - Water diffuses out of capillaries and salt diffuses in • As blood flows back up to the cortex, the opposite occurs • Ascending capillaries of vasa recta - Exchanges salt for water - Water diffuses into and NaCl diffuses out of blood - Vasa recta gives the salt back and does not subtract from the osmolarity of the medulla

Define excretion and identify the systems that excrete wastes.

Excretion—separating wastes from body fluids and eliminating them Four body systems carry out excretion: - Respiratory system • CO2, small amounts of other gases, and water - Integumentary system • Water, inorganic salts, lactic acid, urea in sweat - Digestive system • Water, salts, CO2, lipids, bile pigments, cholesterol, and other metabolic waste - Urinary system • Many metabolic wastes, toxins, drugs, hormones, salts, H+, and water

Describe the process by which the kidney filters the blood plasma, including the relevant cellular structure of the glomerulus.

Kidneys convert blood plasma to urine in four stages: - Glomerular filtration - Tubular reabsorption - Tubular secretion - Water conservation • Glomerular filtrate—the fluid in the capsular space - Similar to blood plasma except that it has almost no protein • Tubular fluid—fluid from the proximal convoluted tubule through the distal convoluted tubule - Substances have been removed or added by tubular cells • Urine—fluid that enters the collecting duct - Undergoes little alteration beyond this point except for changes in water content Glomerular filtration—a special case of capillary fluid exchange in which water and some solutes in the blood plasma pass from the capillaries of the glomerulus into the capsular space of the nephron. • Filtration membrane—three barriers through which fluid passes - Fenestrated endothelium of glomerular capillaries • 70 to 90 nm filtration pores - small enough to exclude blood cells • Highly permeable - Basement membrane • Proteoglycan gel, negative charge, excludes molecules greater than 8 nm • Albumin repelled by negative charge • Blood plasma is 7% protein, the filtrate is only 0.03% protein - Filtration slits • Podocyte cell extensions (pedicels) wrap around the capillaries to form a barrier layer with 30 nm filtration slits • Negatively charged which is an additional obstacle for large anions • Almost any molecule smaller than 3 nm can pass freely through the filtration membrane - Water, electrolytes, glucose, fatty acids, amino acids, nitrogenous wastes, and vitamins • Some substances of low molecular weight are bound to the plasma proteins and cannot get through the membrane - Most calcium, iron, and thyroid hormone • Unbound fraction passes freely into the filtrate

Name and locate the organs of the urinary system.

Kidneys- are large, bean-shaped organs towards the back of the abdomen (belly). They lie behind a protective sheet of tissue within the abdomen. Ureters- are 25-30 cm long tubes lined with smooth muscle that exit the kidneys through the hilum and carry urine to the bladder. Bladder- a pyramid-shaped organ which sits in the pelvis. Urethra- the male urethra is 18-20 cm long, running from the bladder to the tip of the penis. The female urethra is 4-6 cm long and 6 mm wide. It is a tube running from the bladder neck and opening into an external hole located at the top of the vaginal opening.

Describe how the renal tubules reabsorb useful solutes from the glomerular filtrate and return them to the blood.

Two routes of reabsorption: - Transcellular route • Substances pass through cytoplasm of PCT epithelial cells and out their base - Paracellular route • Substances pass between PCT cells • Junctions between epithelial cells are leaky and allow significant amounts of water to pass through • Solvent drag—water carries a variety of dissolved solutes with it • Reabsorbed fluid is ultimately taken up by peritubular capillaries • Sodium reabsorption is key - Creates an osmotic and electrical gradient that drives the reabsorption of water and other solutes - Na+ is most abundant cation in filtrate - Creates steep concentration gradient that favors its diffusion into epithelial cells - Two types of transport proteins in the apical cell surface are responsible for sodium uptake • Symports that simultaneously bind Na+ and another solute such as glucose, amino acids, or lactate • Na+-H+ antiport that pulls Na+ into the cell while pumping out H+ into tubular fluid • Negative chloride ions follow the positive sodium ions by electrical attraction - Various antiports in the apical cell membrane that absorb Cl− in exchange for other anions they eject into the tubular fluid: K +-Cl− symport • Potassium, magnesium, and phosphate ions diffuse through the paracellular route with water • Phosphate is also cotransported into the epithelial cells with Na+ • Some calcium is reabsorbed through the paracellular route in the PCT, but most Ca 2+ reabsorption occurs later in the nephron • Glucose is cotransported with Na+ by sodium-glucose transport (SGLT) proteins - normally all glucose is reabsorbed

Describe the functional anatomy of the ureters, urinary bladder, and male and female urethra.

Ureters - Retroperitoneal, muscular tubes that extend from each kidney to the urinary bladder - About 25 cm long - Pass posterior to bladder and enter it from below - Flap of mucosa at entrance of each ureter acts as a valve into bladder • Keeps urine from backing up into ureter when bladder contracts - Three layers of ureter • Adventitia—connective tissue layer that connects ureter to surrounding structures • Muscularis—two layers of smooth muscle with third layer in lower ureter - Urine enters, it stretches and contracts in peristaltic wave • Mucosa—transitional epithelium - Begins at minor calyces and extends through the bladder - Lumen very narrow, easily obstructed by kidney stones Urinary bladder - Muscular sac located on floor of the pelvic cavity - Inferior to peritoneum and posterior to pubic symphysis • Three layers - Covered by parietal peritoneum, superiorly, and by fibrous adventitia elsewhere - Muscularis: detrusor: three layers of smooth muscle - Mucosa: transitional epithelium • Umbrella cells on surface of epithelium protect it from the hypertonic, acidic urine • Rugae—conspicuous wrinkles in empty bladder • Trigone—smooth-surfaced triangular area on bladder floor that is marked with openings of ureters and urethra • Capacity—moderate fullness is 500 mL, maximum fullness is 700 to 800 mL - Highly distensible - As it fills, it expands superiorly - Rugae flatten - Epithelium thins from five or six layers to two or three Urethra - Is a tube that conveys urine out of body • Female urethra: - 3 to 4 cm long, bound to anterior wall of vagina - External urethral orifice is between vaginal orifice and clitoris • External urethral sphincter - Where urethra passes through the pelvic floor - Skeletal muscle - voluntary control • Male urethra: 18 cm long • Three regions - Prostatic urethra (2.5 cm) • Passes through prostate - Membranous urethra (0.5 cm) • Passes through muscular floor of pelvic cavity - Spongy (penile) urethra (15 cm) • Passes through penis in corpus spongiosum • Internal urethral sphincter - Detrusor muscle thickening • External urethral sphincter - Skeletal muscle of pelvic floor

List several functions of the kidneys in addition to urine formation.

• Filter blood and excrete toxic metabolic wastes • Regulate blood volume, pressure, and osmolarity • Regulate electrolytes and acid-base balance • Secrete erythropoietin, which stimulates the production of red blood cells • Help regulate calcium levels by participating in calcitriol synthesis • Clear hormones from blood • In starvation, they synthesize glucose from amino acids

Explain the forces that promote and oppose filtration, and calculate the filtration pressure if given the magnitude of these forces.

• Filtration pressure depends on hydrostatic and osmotic pressures on each side of the filtration membrane • Blood hydrostatic pressure (BHP) - High in glomerular capillaries (60 mm Hg compared to 10 to 15 in most other capillaries) • Because afferent arteriole is larger than efferent arteriole: a large inlet and small outlet • Hydrostatic pressure in capsular space - 18 mm Hg due to high filtration rate and continual accumulation of fluid in the capsule • Colloid osmotic pressure (COP) of blood - About the same here as elsewhere: 32 mm Hg • Glomerular filtrate is almost proteinfree and has no significant COP • Higher outward pressure of 60 mm Hg, opposed by two inward pressures of 18 mm Hg and 32 mm Hg • Net filtration pressure: 60out − 18in − 32in = 10 mm Hg out - High BP in glomerulus makes kidneys vulnerable to hypertension - It can lead to rupture of glomerular capillaries, produce scarring of the kidneys (nephrosclerosis), and atherosclerosis of renal blood vessels, ultimately leading to renal failure • Glomerular filtration rate (GFR)—amount of filtrate formed per minute by the two kidneys combined - GFR = NFP × Kf ≈ 125 mL/min. or 180 L/day (male) - GFR = NFP × Kf ≈ 105 mL/min. or 150 L/day (female) • Net filtration pressure (NFP) • Filtration coefficient (Kf) depends on permeability and surface area of filtration barrier • Total amount of filtrate produced per day equals 50 to 60 times the amount of blood in the body - 99% of filtrate is reabsorbed since only 1 to 2 L urine excreted per day • If GFR too high - Fluid flows through renal tubules too rapidly for them to reabsorb the usual amount of water and solutes - Urine output rises - Chance of dehydration and electrolyte depletion • If GFR too low - Wastes are reabsorbed - Azotemia may occur

Trace the flow of fluid through the renal tubules.

• Flow of fluid from the point where the glomerular filtrate is formed to the point where urine leaves the body: glomerular capsule → proximal convoluted tubule → nephron loop → distal convoluted tubule → collecting duct → papillary duct → minor calyx → major calyx → renal pelvis → ureter → urinary bladder → urethra

Describe how the nervous system, hormones, and the nephron itself regulate filtration.

• GFR control is achieved by three homeostatic mechanisms: Renal autoregulation • The ability of the nephrons to adjust their own blood flow and GFR without external (nervous or hormonal) control • Enables kidney to maintain a relatively stable GFR in spite of changes in systemic blood pressure • Two methods of autoregulation: myogenic mechanism and tubuloglomerular feedback • Myogenic mechanism—based on the tendency of smooth muscle to contract when stretched - If arterial blood pressure increases • Afferent arteriole is stretched • Afferent arteriole constricts and prevents blood flow into the glomerulus from changing - If arterial blood pressure falls • Afferent arteriole relaxes • Afferent arteriole dilates and allows blood to flow more easily into glomerulus, so that flow rate remains similar and filtration remains stable • Tubuloglomerular feedback— glomerulus receives feedback on the status of downstream tubular fluid and adjusts filtration rate accordingly - Regulates filtrate composition, stabilizes kidney performance, and compensates for fluctuations in blood pressure - Juxtaglomerular apparatus: complex structure found at the end of the nephron loop where it has just reentered the renal cortex - Loop comes into contact with the afferent and efferent arterioles at the vascular pole of the renal corpuscle - Macula densa—patch of slender, closely spaced sensory cells in nephron loop • When GFR is high, filtrate contains more NaCl • When macula densa absorbs more NaCl, it secretes ATP • ATP is metabolized by nearby mesangial cells into adenosine • Adenosine stimulates nearby granular cells - Granular (juxtaglomerular) cells: modified smooth muscle cells wrapping around arterioles (close to macula densa) • Granular cells respond to adenosine by constricting afferent arterioles - Constriction reduces blood flow which corrects GFR - Mesangial cells might also contract, constricting capillaries and further limiting GFR • Granular cells also contain granules of renin, which they secrete in response to drop in blood pressure - Participate in the renin-angiotensin-aldosterone system that works to control blood volume and pressure • Renal autoregulation regulates GFR but cannot keep it entirely constant - Rises in blood pressure will cause a rise in GFR - If mean arterial pressure drops below 70 mm Hg, filtration and urine output cease Sympathetic Control • Sympathetic nerve fibers richly innervate the renal blood vessels • Sympathetic nervous system and adrenal epinephrine constrict the afferent arterioles in strenuous exercise or acute conditions like circulatory shock - Reduces GFR and urine output - Redirects blood from the kidneys to the heart, brain, and skeletal muscles - GFR may be as low as a few milliliters per minute Hormonal control • The renin-angiotensin-aldosterone mechanism is a system of hormones that helps control blood pressure and GFR • In response to a drop in blood pressure, baroreceptors in carotid and aorta stimulate the sympathetic nervous system • Sympathetic fibers trigger release of renin by kidneys' granular cells • Renin converts angiotensinogen, a blood protein, into angiotensin I • In lungs and kidneys, angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II • Angiotensin II—active hormone that increases BP - Potent vasoconstrictor raising BP throughout body - Constricts efferent arteriole raising GFR despite low BP - Lowers BP in peritubular capillaries enhancing reabsorption of NaCl and H2O - Stimulates adrenal cortex to secrete aldosterone, which promotes Na+ and H2O reabsorption in DCT and collecting duct - Stimulates Na+ and H2O reabsorption in PCT - Stimulates posterior pituitary to secrete ADH which promotes water reabsorption by collecting duct - Stimulates thirst

Explain how the nervous system and urethral sphincters control the voiding of urine.

• Micturition—the act of urinating • Between acts of urination, the bladder fills but - Urethral sphincters are tightly closed • Sympathetic activity in upper lumbar spinal cord stimulates postganglionic fibers to the detrusor muscle (relax it) and internal urethral sphincter (excite it) • Somatic motor fibers from upper sacral spinal cord travel through pudendal nerve to supply the external sphincter to allow voluntary control • Two reflexes 1. Involuntary micturition reflex 2. Voluntary reflex Involuntary Micturition Reflex • Stretch receptors detect filing of bladder, transmit afferent signals to spinal cord • Efferent signals return to bladder from spinal cord (S2 and S3) via parasympathetic fibers in the pelvic nerve • Signals excite detrusor muscle • Signals relax internal urethral sphincter (male); urine is involuntary voided external sphincter is not closed Voluntary control • Micturition center in the pons receives signals from stretch receptors • If timely to urinate - Pons returns signals to spinal interneurons that excite detrusor and relax internal urethral sphincter(male) - Cerebral cortex signals open external urethral sphincter • There are times when the bladder is not full enough to trigger the micturition reflex but one wishes to "go" anyway - Valsalva maneuver used to compress bladder - Excites stretch receptors early to get the reflex started.

Describe the location and general appearance of the kidneys.

• Position, weight, and size - Lie against posterior abdominal wall at level of T12 to L3 - Right kidney is slightly lower due to large right lobe of liver - Rib 12 crosses the middle of the left kidney - Retroperitoneal along with ureters, urinary bladder, renal artery and vein, and adrenal glands

Describe how the nephron regulates water excretion.

• Primary function of nephron loop is to generate salinity gradient that enables collecting duct to concentrate the urine and conserve water • Electrolyte reabsorption from filtrate - Thick segment reabsorbs 25% of Na+, K +, and Cl− in filtrate • Ions leave cells by active transport and diffusion - NaCl remains in the tissue fluid of renal medulla - Water cannot follow since thick segment is impermeable - Tubular fluid very dilute as it enters distal convoluted tubule •Fluid arriving in the DCT still contains about 20% of the water and 7% of the salts from glomerular filtrate - If this were all passed as urine, it would amount to 36 L/day • DCT and collecting duct reabsorb variable amounts of water and salt and are regulated by several hormones - Aldosterone, atrial natriuretic peptide, ADH, and parathyroid hormone • Two kinds of cells in the DCT and collecting duct - Principal cells • Most numerous • Have receptors for hormones • Involved in salt and water balance - Intercalated cells • Involved in acid-base balance by secreting H+ into tubule lumen and reabsorbing K+ Aldosterone—the "salt-retaining hormone" - Steroid secreted by the adrenal cortex - Triggers for aldosterone secretion are: • When blood Na+ concentration falls or • When K+ concentration rises or • There is a drop in blood pressure -->renin release --> angiotensin II formation -->stimulates adrenal cortex to secrete aldosterone • Functions of aldosterone - Acts on thick segment of nephron loop, DCT, and cortical portion of collecting duct • Stimulates reabsorption of Na+ and secretion of K+ • Water and Cl− follow the Na+ • Net effect is that the body retains NaCl and water - Helps maintain blood volume and pressure • Urine volume is reduced • Urine has an elevated K+ concentration Natriuretic peptides—secreted by atrial myocardium of the heart in response to high blood pressure • Four actions result in the excretion of more salt and water in the urine, thus reducing blood volume and pressure - Dilates afferent arteriole, constricts efferent arteriole: - Increased GFR - Inhibits renin and aldosterone secretion - Inhibits secretion of ADH - Inhibits NaCl reabsorption by collecting duct Antidiuretic hormone (ADH)- secreted by posterior pituitary - Dehydration, loss of blood volume, and rising blood osmolarity stimulate arterial baroreceptors and hypothalamic osmoreceptors - This triggers release of ADH from the posterior pituitary - ADH makes collecting duct more permeable to water - Water in the tubular fluid reenters the tissue fluid and bloodstream rather than being lost in urine Parathyroid hormone (PTH)- secreted from parathyroid glands in response to calcium deficiency (hypocalcemia) - Acts on PCT to increase phosphate excretion - Acts on the thick segment of the ascending limb of the nephron loop, and on the DCT to increase calcium reabsorption - Increases phosphate content and lowers calcium content in urine - Because phosphate is not retained, calcium ions stay in circulation rather than precipitating into bone tissue as calcium phosphate - PTH stimulates calcitriol synthesis by epithelial cells of the PCT

Trace the flow of blood through the kidney.

• Renal artery divides into segmental arteries that give rise to: - Interlobar arteries: up renal columns, between pyramids - Arcuate arteries: over pyramids - Cortical radiate arteries: up into cortex - Branch into afferent arterioles: each supplying one nephron • Leads to a ball of capillaries—glomerulus - Blood is drained from the glomerulus by efferent arterioles - Most efferent arterioles lead to peritubular capillaries - Some efferents lead to vasa recta—a network of blood vessels within renal medulla - Capillaries then lead to cortical radiate veins or directly into arcuate veins - Arcuate veins lead to interlobar veins which lead to the renal vein • Renal vein empties into inferior vena cava • In the cortex, peritubular capillaries branch off of the efferent arterioles supplying the tissue near the glomerulus, the proximal and distal convoluted tubules • In the medulla, the efferent arterioles give rise to the vasa recta, supplying the nephron loop portion of the nephron

Describe the nerve supply to the kidney

• Renal plexus—nerves and ganglia wrapped around each renal artery - Follows branches of renal artery into the parenchyma of the kidney - Issues nerve fibers to blood vessels and convoluted tubules of the nephron - Carries sympathetic innervation from the abdominal aortic plexus • Stimulation reduces glomerular blood flow and rate of urine production • Respond to falling blood pressure by stimulating the kidneys to secrete renin, an enzyme that activates hormonal mechanisms to restore blood pressure - Kidneys also receive parasympathetic innervation of unknown function

Identify the external and internal features of the kidney.

• Shape and size - About the size of a bar of bath soap - Lateral surface is convex, and medial is concave with a slit, called the hilum • Receives renal nerves, blood vessels, lymphatics, and ureter • Three protective connective tissue coverings - Renal fascia immediately deep to parietal peritoneum • Binds it to abdominal wall - Perirenal fat capsule: cushions kidney and holds it into place - Fibrous capsule encloses kidney protecting it from trauma and infection • Collagen fibers extend from fibrous capsule to renal fascia • Still drop about 3 cm when going from lying down to standing up • Renal parenchyma— glandular tissue that forms urine - Appears C-shaped in frontal section - Encircles renal sinus - Renal sinus: cavity that contains blood and lymphatic vessels, nerves, and urine collecting structures • Two zones of renal parenchyma - Outer renal cortex - Inner renal medulla • Renal columns—extensions of the cortex that project inward toward sinus • Renal pyramids—6 to 10 with broad base facing cortex and renal papilla facing sinus - Lobe of kidney: one pyramid and its overlying cortex - Minor calyx: cup that nestles the papilla of each pyramid; collects its urine - Major calyces: formed by convergence of 2 or 3 minor calyces - Renal pelvis: formed by convergence of 2 or 3 major calyces - Ureter: a tubular continuation of the pelvis that drains urine down to the urinary bladder

Describe how the tubules secrete solute from the blood into the tubular fluid.

• Tubular secretion—renal tubule extracts chemicals from capillary blood and secretes them into tubular fluid • Purposes of secretion in PCT and nephron loop include: - Acid-base balance • Secretion of varying proportions of hydrogen and bicarbonate ions helps regulate pH of body fluids - Waste removal • Urea, uric acid, bile acids, ammonia, and a little creatinine are secreted into the tubule - Clearance of drugs and contaminants • Examples include: morphine, penicillin, and aspirin • Some drugs must be taken multiple times per day to keep up with renal clearance.

Name the major nitrogenous wastes and identify their sources.

• Urea formation - Proteins--> amino acids--> NH2 removed --> forms ammonia - Liver converts ammonia to urea • Uric acid - Product of nucleic acid catabolism • Creatinine - Product of creatine phosphate catabolism