Chapter 26 Urinary System 26 1 Urinary System

Chapter 26 Urinary System 26 -1

Urinary System Functions • Filtering of blood: involves three processesfiltration, reabsorption, secretion. • Regulation of – Blood volume – Concentration of blood solutes: Na+, Cl-, K+, Ca 2+, HPO 4 -2 – p. H of extracellular fluid: secrete H+ – Blood cell synthesis (kidneys secrete hormone, erythropoietin) • Synthesis of vitamin D 26 -2

Urinary System Anatomy 26 -3

Location and External Anatomy of Kidneys • Location – Lie behind peritoneum (retroperitoneal) on posterior abdominal wall on either side of vertebral column – Lumbar vertebrae and rib cage partially protect – Right kidney slightly lower than left • External Anatomy – Renal capsule: fibrous connective tissue. Surrounds each kidney – Perirenal fat • Engulfs renal capsule and acts as cushioning – Renal fascia: thin layer loose connective tissue • Anchors kidneys and surrounding adipose to abdominal wall – Hilum • Renal artery and nerves enter and renal vein and ureter exit kidneys • Opens into renal sinus (cavity filled with fat and loose connective tissue) 26 -4

Internal Anatomy of 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 is boundary between cortex and medulla. Apex of pyramid is renal papilla, points toward sinus. • Calyces – Minor: papillae extend into funnel of minor calyx – Major: converge to form pelvis • Pelvis: enlarged chamber formed by major calyces • Ureter: exits at the hilum; connects to urinary bladder 26 -5

The Nephron • Functional and histological unit of the kidney • Parts of the nephron: Bowman’s capsule, proximal tubule, loop of Henle (nephronic loop), distal tubule • Urine continues from the nephron to collecting ducts, papillary ducts, minor calyses, major calyses, and the renal pelvis • Collecting ducts, parts of the loops of Henle, and papillary ducts are in the renal medulla 26 -6

Types of Nephrons • Juxtamedullary nephrons. Renal corpuscle near the cortical medullary border. Loops of Henle extend deep into the medulla. • Cortical nephrons. Renal corpuscle nearer to the periphery of the cortex. Loops of Henle do not extend deep into the medulla. • Renal corpuscle. Bowman’s capsule plus a capillary bed called the glomerulus. 26 -7

Renal Corpuscle • Bowman’s capsule: outer parietal (simple squamous epithelium) and visceral (cells called podocytes) layers. • Glomerulus: network of capillaries. Blood enters through afferent arteriole, exits through efferent arteriole. 26 -8

Bowman’s 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 that wrap around the glomerular capillaries 26 -9

Filtration Membrane • 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. • 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’s capsule. 26 -10

Circulation in the Glomerulus • • Afferent arteriole: supplies blood to glomerulus Efferent arteriole: drains glomerulus Both vessels have a layer of smooth muscle Juxtaglomerular apparatus: sight of renin production – Juxtaglomerular cells- ring of smooth muscle in the afferent arteriole where the latter enters Bowman’s capsule – Macula densa- Specialized tubule cells of the distal tubule. The distal tubule lies between the afferent and efferent arterioles. 26 -11

Histology of the Nephron • Proximal tubule: simple cuboidal epithelium with many microvilli • Loops of Henle – 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 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 papillary ducts 26 -12

Circulation Through the Kidney Arterial supply: 1. Renal arteries branch from abdominal aorta 2. Segmental arteries branch from renal 3. Interlobar arteries ascend within renal columns toward cortex 4. Arcuate arteries branch and arch over the base of the pyramids 5. Interlobular arteries project into cortex and give rise to afferent arterioles 26 -13

Circulation Through the Kidney • 6. 7. 8. 9. 10. The part of the circulation involved with urine formation Afferent arterioles supply blood to glomerulus Glomerulus Efferent arterioles exit the renal corpuscle Peritubular capillaries form a plexus around the proximal and distal tubules Vasa recta (loop of henle): specialized parts of peritubular capillaries that course into medulla along with loops of Henle, then back toward cortex 26 -14

Circulation Through the Kidney • Venous drainage 11. Peritubular capillaries (PCT) drain into interlobular veins and lead to 12. Arcuate veins 13. Interlobar veins 14. Renal veins 26 -15

Urine Formation Nephrons considered functional units of the kidney: smallest structural component capable of producing urine 26 -16

Filtration • Movement of fluid, derived from blood flowing through the glomerulus, across filtration membrane • Filtrate: water, small molecules, ions that can pass through membrane (large molecules = blood cells & protein-------do not pass) • Pressure difference forces filtrate across filtration membrane • Renal fraction: part of total cardiac output that passes through the kidneys. Varies from 12 -30%; averages 21% • Renal blood flow rate: 1176 m. L/min • Renal plasma flow rate: renal blood flow rate X fraction of blood that is plasma: 650 m. L/min (1176 ml/min x 0. 55 = 646. 8 ml plasma/min) • Filtration fraction: part of plasma flowing through the kidney that is filtered into lumen of Bowman’s capsules; average 19% ( 650 ml plasma/min x 0. 19 = 123. 5 ml plasma/min-----125 ml/min of filtrate) • Glomerular filtration rate (GFR): amount of filtrate produced each minute. 180 L/day • Average urine production/day: 1 -2 L. Most of filtrate must be 26 -17 reabsorbed

26 -18

Filtration • Filtration membrane: filtration barrier. It prevents blood cells and proteins from entering lumen of Bowman’s capsule, but is many times more permeable than a typical capillary – Fenestrated endothelium, basement membrane and pores formed by podocytes – Some albumin and small hormonal proteins enter the filtrate, but these are reabsorbed and metabolized by the cells of the proximal tubule. Very little protein normally found in urine • Filtration pressure: pressure gradient responsible for filtration; forces fluid from glomerular capillary across membrane into lumen of Bowman’s capsules • Forces that affect movement of fluid into or out of the lumen of Bowman’s capsule – Glomerular capillary pressure (GCP): blood pressure inside capillary tends to move fluid out of capillary into Bowman’s capsule – Capsule pressure (CP): 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) – CP (10 mm Hg) – 26 -19 BCOP (30 mm Hg)

Filtration Pressure 26 -20

Filtration • 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 • Filtrate is forced across filtration membrane; fluid moves into peritubular capillaries from interstitial fluid • Changes in afferent and efferent arteriole diameter alter filtration pressure – Dilation of afferent arterioles/constriction efferent arterioles increases glomerular capillary pressure, increasing filtration pressure and thus glomerular filtration 26 -21

Autoregulation and Sympathetic Stimulation • Autoregulation – Involves changes in degree of constriction in afferent arterioles – As systemic BP increases, afferent arterioles constrict and prevent increase in renal blood flow (opposite also occurs) – Increased rate of blood flow of filtrate past cells of macula densa: signal sent to juxtaglomerular apparatus, afferent arteriole constricts • Sympathetic stimulation: norepinephrine – Constricts small arteries and afferent arterioles – Decreases renal blood flow and thus filtrate formation – During shock or intense exercise: intense sympathetic stimulation, rate of filtrate formation drops to a few ml *Note: Glomerular filtration rate is relatively constant as B. P. changes 26 -22 between 90 & 180 mm. Hg.

Tubular Reabsorption: Overview • Tubular reabsorption: occurs as filtrate flows through the lumens of proximal tubule, loop of Henle, distal tubule, and collecting ducts • Results because of – – – Diffusion Facilitated diffusion Active transport Symport Osmosis • Substances transported to interstitial fluid and reabsorbed into peritubular capillaries: inorganic salts, organic molecules, 99% of filtrate volume. These substances return to general circulation through venous 26 -23 system

Reabsorption in Proximal Convoluted Tubule • Substances pass through cells of tubule wall. Each cell has – Apical surface: surface that faces filtrate. Apical membrane – Basal surface: faces interstitial fluid. Basal membrane – Lateral surfaces: surfaces between cells • Active transport of Na+ across the basal membrane from cytoplasm to interstitial fluid linked to reabsorption of most solutes • Because of active transport, the concentration of Na+ is low inside the cell and Na+ moves into nephron cell from filtrate through the apical membrane. Other substances moved by symport from the filtrate into the nephron cell are substances that should be retained by the body • Substances transported –Through apical membrane: Na+, Cl-, glucose, amino acids, and water. –Through basal membrane: Na+, K+, Cl-, glucose, amino acids, water 26 -24

Reabsorption in Proximal Convoluted Tubule • Number of carrier molecules limits rate of transport • In diabetes mellitus – Concentration of glucose in filtrate exceeds rate of transport – High concentration of glucose in plasma (and thus in filtrate) reflected in glucose in the urine • Diffusion between cells: from lumen of nephron into interstitial fluid – Depends on rate of transport of some solutes through the cells of the tubule – K+, Ca 2+, and Mg 2+ • Filtrate volume reduced by 65% due to osmosis of water 26 -25

Reabsorption in Loop of Henle • Loop of Henle descends into medulla; interstitial fluid is high in solutes. • Descending thin segment is highly permeable to water and moderately permeable to urea, sodium, most other ions (passive). • Water moves out of nephron, solutes in. Volume of filtrate reduced by another 15%. • Ascending thin segment is not permeable to water, but is permeable to solutes. Solutes diffuse out of the tubule and into the more dilute interstitial fluid as the ascending limb projects toward the cortex. Solutes diffuse into the descending vasa recta. 26 -26

Reabsorption in Loop of Henle • The wall of the ascending limb of the loop of Henle is not permeable to water. Na+ moves across the wall of the basal membrane by active transport, establishing a concentration gradient for Na+. K+ and Cl- are symported with Na across the apical membrane and ions pass by facilitated diffusion across the basal cell membrane of the tubule cells. • At the end of the loop of Henle, inside of nephron concentration of solutes is 100 m. Osm/kg (milli-osmole per kilogram). Interstitial fluid in the cortex is 300 m. Osm/kg. Filtrate within DCT is much more dilute than the interstitial fluid which surrounds it. 26 -27

Reabsorption in Distal Convoluted Tubule and Collecting Duct • Active transport of Na+ out of tubule cells into interstitial fluid with cotransport of Cl • Na+ moves from filtrate into tubule cells due to concentration gradient • Collecting ducts extend from cortex (interstitial fluid 300 m. Osm/kg) through medulla (interstitial fluid very high) • Water moves by osmosis from distal tubule and collecting duct into more concentrated interstitial fluid • Permeability of wall of distal tubule and collecting ducts have variable permeability to water • Urine can vary in concentration from low volume of high concentration to high volume of low concentration 26 -28

Changes in Concentration of Solutes in the Nephron • Urea: enters glomerular filtrate. – As volume of filtrate decreases (approx. 99% H 2 O is reabsorbed), concentration of urea increases – Walls of nephron not very permeable to urea: only 4060% passively reabsorbed • Urate ions, creatinine, sulfates, phosphates, nitrates partially reabsorbed – Concentration is high in urine – Toxic substances and are eliminated 26 -29

Tubular Secretion • Moves metabolic by-products, drugs, molecules not normally produced by the body into tubule of nephron • Active or passive • Ammonia: produced by epithelial cells of nephron from deamination of amino acids. Diffuses into lumen • H+, K+, penicillin, and substances such as paraaminohippuric acid (PAH): actively secreted into nephron 26 -30

Secretion of Hydrogen and Potassium A. Hydrogen ions secreted into filtrate by countertransport in proximal tubule – H+ either diffuse from peritubular capillaries into interstitial fluid and then into epithelial cells of tubule or derived from reaction between carbon dioxide and water in cells of tubule. – Na+ and HCO 3 - cotransported across basal membrane into interstitial fluid, then diffuse into peritubular capillaries 26 -31

Secretion of Hydrogen and Potassium B. H+ and K+ secreted into filtrate by countertransport in distal tubule. Na+ and K+ move by active transport across the basal membrane. Na+ and HCO 3 cotransported across basal membrane into interstitial fluid, then diffuse into peritubular capillaries 26 -32

Urine Production • In Proximal convoluted tubules – Na+ and other substances removed – Water follows passively – Filtrate volume reduced • In descending limb of loop of Henle – Water exits passively, solute enters – Filtrate volume reduced 15% • In ascending limb of loop of Henle – Na+, Cl-, K+ transported out of filtrate – Water remains • In distal convoluted tubules and collecting ducts – Water movement out regulated by ADH • If absent, water not reabsorbed and dilute urine produced • If ADH present, water moves out, concentrated urine produced 26 -33

Urine Concentration Mechanism • When large volume of water consumed – Eliminate excess without losing large amounts of electrolytes – Response is that kidneys produce large volume of dilute urine • When drinking water not available – Kidneys produce small volume of concentrated urine – Removes waste and prevents rapid dehydration • Mechanisms that create urine of variable concentration – Maintenance of high concentration of solutes in medulla – Countercurrent functions of loops of Henle – Control of permeability of distal nephron to water 26 -34

Medullary Concentration Gradient • In order to concentrate urine (and prevent a large volume of water from being lost), the kidney must maintain a high concentration of solutes in the medulla • Interstitial fluid concentration (m. Osm/kg) is 300 in the cortical region and gradually increases to 1200 at the tip of the pyramids in the medulla • Maintenance of this gradient depends upon – Functions of loops of Henle – Vasa recta flowing countercurrent to filtrate in loops of Henle – Distribution and recycling of urea 26 -35

Creating/Maintaining High Solute Concentration in Medulla • Active transport of Na+ and cotransport of ions such as K+ and Cl- and other ions out of the thick portion of ascending limb into interstitial fluid • Impermeability of thin and thick parts of ascending limb of loop of Henle to water • Vasa recta remove excess water and solutes that enter the medulla without destroying the high concentration of solutes in interstitial fluid of medulla • Active transport of ions from collecting ducts into interstitial fluid of medulla • Passive diffusion of urea from collecting ducts into interstitial fluid of medulla, impermeability of the ascending limb and permeability of the descending limb of the loops of Henle to 26 -36 urea

Loops of Henle • Juxtamedullary nephrons: long loops. – Walls of descending limbs permeable to water, water moves out into interstitial fluid – Walls of ascending limb impermeable to water – Solute diffuses out of thin segment of ascending limb as it passes though progressively less concentrated interstitial fluid – Na+, K+ and Cl- actively transported out of ascending limb into interstitial fluid – Thus, water enters interstitial fluid from descending limbs and solutes enter interstitial fluid from ascending limbs 26 -37

Vasa Recta • Countercurrent systems that remove excess water and solutes from medulla: parallel tubes in which fluid flows, but in opposite directions • Blood flows through vasa recta to the medulla, vessels turn near tip of renal pyramid, then blood flows in opposite direction • Walls are permeable to water and to solutes: as blood flows toward medulla, water moves out, solutes diffuse in. As blood flows back toward cortex, water moves into vasa recta, some solutes diffuse out • Diffusion is such that slightly more water and slightly more solute are carried from the medulla by the vasa recta than enter it 26 -38

• Loops of Henle and vasa recta function together to maintain a high concentration of solutes in the interstitial fluids of the medulla and to carry away the water and solutes that enter the medulla from the loops of Henle and collecting ducts – Water moves out of descending limb and enters vasa recta – Solutes diffuse out of ascending thin segment and enter vasa recta, but water does not – Solutes transported out of thick segment of ascending enter the vasa recta – Excess water and solutes carried away from medulla without reducing high concentration of solutes – Concentration of filtrate reduced to 100 m. Osm/kg by the time it reaches distal tubule 26 -39

• Water and solutes move out of the collecting duct into the vasa recta 26 -40

Urea • Responsible for large part of high osmolality in medulla • Descending limbs of loops of Henle permeable to urea; urea diffuses into interstitial fluid • Ascending limbs and distal tubules impermeable to urea • Collecting ducts permeable to urea; some diffuses out into interstitial fluid • Urea flows in a cycle maintaining high urea concentration in medulla 26 -41

Urine Concentrating Mechanisms 26 -42

Renin/Angiotensin/Aldosterone 26 -43

ADH and the Nephron 26 -44

ADH and the Nephron 26 -45

Other Hormones • Atrial natriuretic hormone – Produced by right atrium of heart when blood volume increases stretching cells – Inhibits Na+ reabsorption – Inhibits ADH production – Increases volume of urine produced – Venous return is lowered, volume in right atrium decreases • Prostaglandins and kinins: produced in kidney. Role unclear 26 -46

Clearance and Tubular Maximum • Plasma clearance: calculated using substances like inulin – Volume of plasma cleared of a specific substance each minute – Used to estimate GFR – Used to calculate renal plasma flow. Calculated using substances like PAH – Used to determine which drugs or other substances excreted by kidney • Tubular load – Total amount of substance that passes through filtration membrane into nephrons each minute 26 -47

Tubular Maximum • Maximum rate at which a substance can be actively absorbed – Each substance has its own tubular maximum – Normally, glucose concentration in the plasma (and thus filtrate) is lower than the tubular maximum and all of it is reabsorbed; none of it is found in the urine – In diabetes mellitus tubular load exceeds tubular maximum and glucose appears in urine. Urine volume increases because glucose in filtrate increases osmolality of filtrate reducing the effectiveness of water reabsorption 26 -48

Urine Movement • 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 -3 minutes – Parasympathetic stimulation: increase frequency – Sympathetic stimulation: decrease frequency • Ureters enter bladder obliquely through trigone. Pressure in bladder compresses ureter and prevents backflow 26 -49

Anatomy and Histology of Ureters and Bladder • 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 • 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 26 -50

Anatomy and Histology of Urethra • Male: extends from the inferior part of the urinary bladder through the penis • Female: shorter; opens into vestibule anterior to vaginal opening • Internal urinary sphincter: in males, elastic connective tissue and smooth muscle keep semen from entering urinary bladder during ejaculation • External urinary sphincter: skeletal muscle surrounds urethra as it extends through pelvic floor. Acts as a valve 26 -51

Micturition Reflex 26 -52

Effects of Aging • Gradual decrease in size of kidneys, but only onethird 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 Ca 2+ deficiency, osteoporosis, and bone fractures 26 -53