Urinary System

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Chapter 26

• Urinary System

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Urinary System Functions

• Filtering of blood involves three processes-
  filtration, reabsorption, secretion.
• Regulation of
• Blood volume
• Concentration of blood solutes Na, Cl-, K,
  Ca2, HPO4-2
• pH of extracellular fluid secrete H
• Blood cell synthesis (kidneys secrete
  hormone,erythropoietin)
• Synthesis of vitamin D

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Urinary System Anatomy
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Location and External Anatomyof Kidneys

• 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)

• 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

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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

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The Nephron

• Functional and histological unit of the kidney
• Parts of the nephron Bowmans 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

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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. Bowmans capsule plus a
  capillary bed called the glomerulus.

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Renal Corpuscle

• Bowmans 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.

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Bowmans Capsule

• Parietal layer outer. Simple squamous epithelium
  that becomes cube-shaped where Bowmans capsule
  ends and proximal tubule begins
• Visceral layer inner. Specialized podocytes that
  wrap around the glomerular capillaries

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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 Bowmans capsule.

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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
  Bowmans capsule
• Macula densa- Specialized tubule cells of the
  distal tubule. The distal tubule lies between the
  afferent and efferent arterioles.

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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

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Circulation Through the Kidney

• Arterial supply
• Renal arteries branch from abdominal aorta
• Segmental arteries branch from renal
• Interlobar arteries ascend within renal columns
  toward cortex
• Arcuate arteries branch and arch overthe base of
  the pyramids
• Interlobular arteries project into cortex and
  give rise to afferent arterioles

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Circulation Through the Kidney

• The part of the circulation involved with urine
  formation
• Afferent arterioles supplyblood to glomerulus
• Glomerulus
• Efferent arterioles exit therenal 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

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Circulation Through the Kidney

• Venous drainage
• Peritubular capillaries (PCT) drain into
  interlobular veins and lead to
• Arcuate veins
• Interlobar veins
• Renal veins

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Urine Formation

• Nephrons considered functional units of the
  kidney smallest structural component capable of
  producing urine

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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 mL/min
• Renal plasma flow rate renal blood flow rate X
  fraction of blood that is plasma 650 mL/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
  Bowmans 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 reabsorbed

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Filtration

• Filtration membrane filtration barrier. It
  prevents blood cells and proteins from entering
  lumen of Bowmans 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 Bowmans capsules
• Forces that affect movement of fluid into or out
  of the lumen of Bowmans capsule
• Glomerular capillary pressure (GCP) blood
  pressure inside capillary tends to move fluid out
  of capillary into Bowmans 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) BCOP (30 mm Hg)

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Filtration Pressure
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Filtration

• Colloid osmotic pressure in Bowmans 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

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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 between 90 180
  mmHg.

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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 system

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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

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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, Ca2, and Mg2
• Filtrate volume reduced by 65 due to osmosis of
  water

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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.

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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 mOsm/kg
  (milli-osmole per kilogram). Interstitial fluid
  in the cortex is 300mOsm/kg. Filtrate within DCT
  is much more dilute than the interstitial fluid
  which surrounds it.

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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 mOsm/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

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Changes in Concentration of Solutes in the Nephron

• Urea enters glomerular filtrate.
• As volume of filtrate decreases (approx. 99 H2O
  is reabsorbed), concentration of urea increases
• Walls of nephron not very permeable to urea only
  40-60 passively reabsorbed
• Urate ions, creatinine, sulfates, phosphates,
  nitrates partially reabsorbed
• Concentration is high in urine
• Toxic substances and are eliminated

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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
  para-aminohippuric acid (PAH) actively secreted
  into nephron

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Secretion of Hydrogen and Potassium

• 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 HCO3- cotransported across basal membrane
  into interstitial fluid, then diffuse into
  peritubular capillaries

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Secretion of Hydrogen and Potassium

1. H and K secreted into filtrate by
   countertransport in distal tubule. Na and K
   move by active transport across the basal
   membrane. Na and HCO3- cotransported across
   basal membrane into interstitial fluid, then
   diffuse into peritubular capillaries

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Urine Production

• 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

• 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

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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

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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 (mOsm/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

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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 urea

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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

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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

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• 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 mOsm/kg
  by the time it reaches distal tubule

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

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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

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Urine Concentrating Mechanisms
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Renin/Angiotensin/Aldosterone
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ADH and the Nephron
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ADH and the Nephron
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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

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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

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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

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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

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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

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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

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Micturition Reflex
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Effects of Aging

• 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