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Lecture Presentation - Urinary system

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									The Urinary System
   Kidneys
     –   Functional components
         of urinary system
             Partially protected by
              11th - 12th pairs of ribs
             Right kidney slightly

   ureters
   urinary bladder
   urethra
   Functions of the kidneys include:
     –   Regulating blood ionic composition
             Na+, K+, Ca2+, Cl-, HPO42-
     –   Regulating blood pH
             Excrete variable amounts of H+ and conserve and produce bicarbonate
     –   Regulating blood volume
             Conserve and eliminate variable amounts of water in urine
     –   Regulating blood pressure
             Via regulation of blood volume as well as vasoconstrictive effects of ADH
     –   Maintaining blood osmolarity (no. of dissolves particles per litre of
             Separately regulates loss of water and solutes
     –   Producing hormones
             Calcitriol – active form of vitamin D
             EPO – stimulates production of erythrocytes
     –   Regulating blood glucose level
             Carries out gluconeogenesis
     –   Excreting wastes and foreign substances
    Kidney anatomy
   Renal capsule
     –   protection

     –   maintains kidney shape

   Adipose capsule
     –   protection

     –   holds kidney in place
             Nephroptosis may occur in
              very thin people

   Renal fascia
     –   anchors to surrounding
         structures and abdominal wall
   Renal Hilus
    –   ureters, blood vessels,
        lymphatic vessels and nerves
        enter and exit kidney
   Structure:
    –   Cortex
    –   Medulla
            columns
                 –   Extension of cortex
                     providing route for nerves
                     and blood vessels
            pyramids
                 –   Papillary ducts run into
                     apex (papilla)
    –   Minor and major calyces
    –   Renal pelvis
         Nerve and blood supply of
   Kidneys receive 20-25% of resting
    cardiac output
   Each nephron receives an afferent
     –   Divides into ball shaped capillary network
         called glomerulus
              Glomerular capillaries reunite to form
               efferent arteriole
                  –   Carries blood out of glomerulus
     –   Vasa recta and peritubular capillaries
         extend from some efferent arterioles
              Supply blood to tubular portions of
     –   Renal nerves part of sympathetic division
         of ANS
              Most are vasomotor nerves that regulate
               blood flow through kidney
   Nephron
    –   functional unit of the
            Consists of:
               –   Renal corpuscle
                     • Glomerulus
                     • Bowman’s capsule
               –   Renal tubule
                     • proximal convoluted
                     • loop of Henle
                     • distal convoluted
   Two classifications of
     –   Cortical (80-85%)
             glomerulus in outer cortex
             short loop of Henle
                –   penetrates to outer
     –   Juxtamedullary (15-20%)
             glomerulus deep in cortex
             long loop of Henle
                –   Ascending limb has two
                        • Thin ascending
                        • Thick ascending
                –   Penetrates deep into
                –   Establish high osmolarity
                    in renal medulla
   Nephron performs 3 functions:
    –   glomerular filtration
            Water and most solutes in blood
             plasma move across glomerular
             capillaries into capsular space
             then into renal tubule
    –   tubular reabsorption
            Tubule cells reabsorb ~99% of
             filtered water and useful solutes
    –   tubular secretion
            Tubule and duct cells secrete
             wastes, drugs, excess ions into
         Glomerular filtration
   Endothelial cells of glomerular
    capillaries encircled by podocytes
     –   Pedicels of podocytes form filtration
   Filtration membrane
                Permits filtration of water and
                 small solutes but not blood
                 cells, platelets or most plasma
   Mesangial cells
     –   Located among glomerular
                Regulate diameter of capillaries
    Glomerular filtration

   Net filtration
    pressure depends on
     –   glomerular blood
         hydrostatic pressure

     –   capsular hydrostatic

     –   blood colloid
         osmotic pressure
    Clinical note

   In some kidney diseases
    glomerular capillaries are
     –   Plasma proteins enter
         glomerular filtrate
             Reduces blood coloid
              osmotic pressure
                –   More fluid moves into
                                            From: http://renux.dmed.ed.ac.uk/EdREN/EdRenINFObits/NephroticLong.html
                      •   Causes edema
Glomerular filtration rate

   Glomerular Filtration Rate (GFR)
     –   Volume of filtrate formed in all renal corpuscles of both kidneys each
             Averages 125 ml/min
             If GFR too high
                –   substances pass too quickly through tubules for adequate reabsorption
                       •   Excess urinary loss
             If GFR too low
                –   Nearly all filtrate reabsorbed
                       •   Certain wastes may not be adequately excreted
     –   GFR remains relatively constant due to:
             Adjustments in glomerular blood flow
             Alteration of glomerular capillary surface area available for filtration
                –   Mesangial cells regulate this
Glomerular filtration rate

        GFR controlled by:
         –   Renal autoregulation

         –   Neural regulation

         –   Hormonal regulation
Renal autoregulation of GFR

   Renal autoregulation of GFR
     –   Two mechanisms
             Myogenic
                –   Stretching triggers contraction of smooth muscle cells in wall of afferent

                       •   Glomerular blood flow reduces

                       •   GFR reduces

                –   Normalises GFR within seconds after a change in blood pressure

             Tubuloglomerular feedback
                –   Macula densa provides feedback to regulate diameter of afferent arteriole
                    via the juxtaglomerular apparatus
    Juxtaglomerular apparatus
   Final part of ascending limb of LOH
    makes contact with afferent arteriole
   Tubule cells in this region of LOH
    crowded together
     –   macula densa
              detect changes in delivery of Na+,
               Cl- and H20
   Wall of afferent arteriole contains
    modified smooth muscle cells
     –   Juxtaglomerular cells
              release nitric oxide which adjusts
               diameter of afferent arteriole
   Macula Densa and Juxtaglomerular
    cells together make
    Juxtaglomerular apparatus
    Tubuloglomerular regulation of GFR

   When GFR high less time for
    reabsorption of Na+, Cl- and
     –    macula densa detects increased
          delivery of Na+, Cl- and H20.

     –    NO release by juxtaglomerular
          cells inhibited
              Afferent arteriole constricts
                 –   Decreases blood flow
                     through afferent arteriole
                     and decreases GFR
Neural regulation of GFR

     Blood vessels in kidneys supplied by sympathetic ANS fibres
       –   Stimulation (such as during exercise etc) causes constriction of
           afferent arteriole
                Reduces GFR
                   –   Reduces urine output so as to conserve blood volume

                   –   Permits greater blood flow to other tissues
Hormonal regulation of GFR

     ANP
       –   Released by atria when stretched (high blood volume / high BP)
                Causes relaxation of glomerular mesangial cells
                    –   Increases capillary surface area for filtration

                           •   GFR increases

     Angiotensin II
       –   Vasoconstrictor formed in response to low blood pressure
                Causes constriction of afferent (and efferent arterioles)
                    –   Reduces GFR

                           •   Increases reabsorption to increase BP
Tubular reabsorption
   Normal rate of GFR (~125 ml/min) means that the volume of fluid entering the
    PCT in ½ hour is greater than total plasma volume
     –   Normally ~99% of filtered water and solute reabsorbed
              PCT makes major contribution to reabsorption

              More distal tubules fine tune reabsorption to maintain water and ion balance

     –   Solute reabsorption drives water reabsorption because all water reabsorption occurs
         via osmosis
              Obligatory water reabsorption
                  –   Water reabsorbed with solutes (water ‘obliged’ to follow solutes)

                         •   Occurs in PCT and descending LOH – always permeable to H2O

              Facultative water reabsorption
                  –   Ability of water to follow solute dependent on availability of ADH

                         •   Occurs mainly in collecting ducts
Reabsorption and secretion - PCT
   Largest amount of solute and water reabsorption occurs in PCT
     –   Most absorptive processes involve Na+

     –   Filtered glucose, amino acids, lactic acid, vitamins and other nutrients reabsorbed
         by Na+ symporters

     –   Na+ also reabsorbed by Na+/H+ antiporters
              Can provide mechanism for reducing blood H+

              PCT cells can produce own H+ to keep antiporter running to ensure adequate Na+
                  –   H+ produced by carbonic anhydrase reaction

                         •    HCO3- produced from carbonic anhydrase reaction reabsorbed

                  –   NH4+ can substitute for H+

                         •    Produced by deamination of glutamine

                         •    Also produces HCO3- which is reabsorbed

              Reabsorption of solutes promotes water reabsorption via osmosis (obligatory water
Reabsorption – Loop of Henle

   Reabsorption of water via osmosis
    not automatically coupled to
    reabsorption of solutes
     –   Descending LOH permeable to
         water, relatively impermeable to
              Water reabsorbed via osmosis

     –   Ascending limb of LOH permeable
         to solutes, relatively impermeable
         to water
              Solutes reabsorbed via Na+-K+-
               2Cl- symporters
Reabsorption – DCT

   Reabsorption of Na+ and Cl- via
    Na+-Cl- symporters

   Relatively impermeable to
     –   Does not follow via obligatory
         water reabsorption

   Major target for parathyroid
    hormone stimulated increase in
    Ca2+ reabsorption
Reabsorption and secretion – collecting ducts

     By time filtrate reaches end of
      DCT 90-95% of filtered solutes
      and water have been reabsorbed

     Collecting ducts relatively
      impermeable to water
       –   Water reabsorption under
           facultative control
Hormonal regulation of tubular reabsorption
and secretion

        Most important regulators of tubular electrolyte
         reabsorption and secretion are
          –   Angiotensin II

          –   Aldosterone

        Major hormone regulating tubular water reabsorption is
Renin – angiotensin – aldosterone system

   When BP and BV low walls of afferent arteriole stretched
    –   Reduced stretch causes juxtaglomerular cells to release renin
               –   Renin also released in response to sympathetic stimulation
            Renin clips off 10 amino acid peptide called angiotensin I from
             angiotensinogen (plasma protein)
            Angiotensin I converted to angiotensin II (active) in lungs by ACE
             (angiotensin converting enzyme) clipping off another 2 amino acids
            Angiotensin II
               –   constricts afferent arterioles
                      •   reduces GFR and allows more time for reabsorption
               –   stimulates Na+, Cl-, and water reabsorption in PCT
               –   stimulates aldosterone secretion by adrenal cortex
                      •   increases reabsorption of Na+, Cl- and H20 in collecting ducts
                      •   Also stimulates thirst centre in hypothalamus
    Antidiuretic hormone
   ADH released by posterior pituitary
     –   Secretion regulated by negative
              Hypothalamic osmoreceptors
               regulate secretion of ADH in
               response to changes in blood

     –   ADH regulates facultative water
         reabsorption in last part of DCT and
         collecting ducts
              Stimulates insertion of water channel
               (aquaporin-2) into apical membranes of
               principal cells
Urine production

       Homeostasis of body fluid volume depends in
        large part on the ability of the kidneys to
        regulate the rate of water loss in urine

       ADH controls whether dilute or concentrated
        urine is formed
    Producing dilute urine
   Descending limb of LOH
     –    permeable to water
     –   impermeable to solutes
             Water moves out solutes
              cannot follow
   Ascending limb and collecting
     –   permeable to solutes (active
             Contribute to medullary osmotic
     –   impermeable to water
         (dependent on ADH)
             Solutes actively transported
              out but water cannot follow
         Producing concentrated urine
   Production of concentrated urine is
    dependent on a high osmotic
    gradient in the renal medulla
   High osmotic gradient established
    by juxtamedullary nephrons:
     –   Thick ascending limb cells of LOH
         reabsorb ions from filtrate and pass
         into medulla
     –   Urea recycling
              Urea recycled from distal tubule to
               medulla and equilibrates with LOH
                  –   Maintains medullary osmolarity
     –   Sluggish flow of blood in vasa recta
         allows equilibrium with medullary
              ie blood does not remove solutes
               and destroy gradient
     Producing concentrated urine

   ADH increases insertion of

    aquaporin-2 in collecting ducts

     –   When filtrate passes through

         high osmolarity of deep renal

         medulla water moves according

         to osmotic gradient

     –   Results in concentrated urine
    Clinical note - diuretics

   Diuretics slow renal reabsorption of


     –   Most act by blocking Na+ transporters

               Less Na+ reabsorbed

                  –   Less water reabsorbed by obligatory


     –   Cause diuresis (increased urine
         production)                                                               ?oneclick=true

               Reduces plasma volume

                  –   Reduces edema
    Urine transport, storage and
   Urine drains from collecting ducts into calyces, renal pelvis and then ureters

   Stored in urinary bladder

     –   Average capacity 700-800 ml

     –   Sensation of fullness initiates conscious desire to urinate before bladder ½ full

   Once bladder approx ½ full stretch receptors in bladder wall transmit afferent

    nerve impulses to micturition centre in sacral spinal cord

     –   Efferent impulses cause contraction of detrusor muscle (lines wall of bladder) and

         relaxation of internal urethral sphincter muscle

              Micturition can be delayed through conscious contraction of external urethral sphincter

               (skeletal muscle)
Aging and the urinary system
         Kidneys shrink in size
           –   Reduced blood flow
                    Filter less blood

         Sensation of thirst diminishes with age
           –   Increased dehydration

         Urinary dysfunction more prevalent
           –   Polyuria – excessive urine production
           –   Nocturia – excessive urination at night
           –   Dysuria – painful urination
           –   Incontinence
           –   hematuria

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