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Human Physiology Chapter 17 Notes

by: MBattito

Human Physiology Chapter 17 Notes BIOL 3160

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These notes cover material from chapter 17 that was covered in the power points, lecture and textbook.
Human Physiology
Dr. Tamara McNutt-Scott
Class Notes
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This 11 page Class Notes was uploaded by MBattito on Wednesday April 20, 2016. The Class Notes belongs to BIOL 3160 at Clemson University taught by Dr. Tamara McNutt-Scott in Fall 2015. Since its upload, it has received 20 views. For similar materials see Human Physiology in Biological Sciences at Clemson University.


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Date Created: 04/20/16
Chapter  17:  Physiology  of  the  Kidneys     Primary  function  of  kidneys  is  in  the  regulation  of  the  extracellular  fluid  (plasma   and  interstitial  fluid)  environment  of  the  body   • Accomplished  through  formation  of  urine   o During  this  process,  kidneys  regulate   § Volume  of  blood  plasma  à  contribute  significantly  to  the   regulation  of  blood  pressure   § Concentration  of  waste  products  in  blood   § Concentration  of  electrolytes  (Na,  K,  HCO3,  etc.)   § pH  of  plasma   • Kidneys  considered  most  potent  acid-­‐base  regulator   Gross  Anatomy  of  the  Urinary  System   • Kidneys:  lie  on  either  side  of  the  vertebral  column  below  the  diaphragm  and   liver   o About  the  size  of  a  fist   o Coronal  Section  of  kidney  has  2  regions   § Outer  renal  cortex  –  reddish  brown  and  granular  because  of   numerous  capillaries   § Deeper  renal  medulla  –  striped  due  to  the  presence  of   microscopic  tubules  and  blood  vessels   • Composed  of  8-­‐15  conical  renal  pyramids  separated  by   renal  columns   o Cavity  of  the  kidney  is  divided  into  several  portions   § Minor  calyx  –  small  depression  that  each  pyramid  projects  into   § Major  calyx  –  formed  by  union  of  several  minor  calyces  à   major  calyces  join  to  form  renal  pelvis     • Renal  pelvis:  cavity  where  urine  produced  in  the  kidneys  is  drained  to     o Urine  then  channeled  from  the  kidneys  to  the  urinary  bladder  through   the  ureters     o Ureters:  long  ducts  that  undergo  peristalsis  (wave-­‐like  contractions)   § Pacemaker  of  these  peristaltic  waves  is  located  in  the  renal   calyces  and  pelvis,  which  contain  smooth  muscle  –  renal   calyces  and  pelvis  also  undergo  peristalsis  to  aid  emptying  of   urine  from  kidney   • Urinary  bladder:  storage  sac  for  urine   o Shape  is  determined  by  amount  of  urine  it  contains   § Empty  =  pyramidal   § As  it  fills  =  ovoid  and  bulges  into  abdomen     o Drained  inferiorly  by  urethra   o Has  a  muscular  wall  –  detrusor  muscle     Microscopic  Anatomy  of  the  Kidney   • Nephron  –  functional  unit  of  the  kidney   o Responsible  of  urine  formation   o Comprised  of  renal  corpuscle  and  renal  tubules   § Renal  corpuscle  –  glomerulus  and  Bowman’s  capsule   • Glomerular  filtration   § Renal  tubules  –  proximal  convoluted  tubule,  distant  convoluted   tubulues  and  Loop  of  Henle   • Tubular  secretion     • Tubular  absorption     o 2  types:   § Cortical  –  original  in  the  outer  2/3  of  the  cortex   • More  numerous   § Juxtamedullary  –  originate  in  the  inner  1/3  of  the  cortex  (next   to  the  medulla)   • Have  longer  nephron  loops   • Play  an  important  role  in  kidney’s  ability  to  produce  a   concentrated  urine   • Glomerular  (Bowman’s)  capsule:  surrounds  the  glomerulus     o Contains  an  inner  visceral  layer  and  outer  parietal  layer   o Space  between  the  two  layers  is  continuous  with  the  lumen  of  the   tubule   o Filtrate  that  enters  glomerular  capsule  passes  into  lumen  of  the   proximal  convoluted  tubule   § Proximal  convoluted  tubule  contains  millions  of  microvilli  to   increase  surface  area  for  reabsorption   § See  absorption   o Fluid  passes  from  the  proximal  convoluted  tubule  to  the  nephron  loop   (Loop  of  Henle)     § This  fluid  is  carries  into  the  medulla  in  the  descending  limb  of   the  loop  and  returns  to  the  cortex  in  the  ascending  limb   o Distal  convoluted  tubule:  coiled  tubule  in  the  cortex   § See  secretion   § Shorter  than  proximal  tubule     § Relatively  few  microvilli     § Terminates  as  it  empties  into  a  collecting  duct   o Collecting  duct:  receives  fluid  from  the  distal  convoluted  tubule  of   several  nephrons   § Fluid  is  drained  by  the  collecting  duct  from  the  cortex  to  the   medulla  as  the  collecting  duct  passes  through  a  renal  pyramid   § Fluid  is  now  called  urine  à  passes  into  minor  calyx  à   funneled  through  renal  pelvis  out  of  the  kidney  into  the  ureter   • Vasculature   o Renal  artery:  where  arterial  blood  enters  kidney   o Renal  artery  divides  into  interlobular  arteries  that  pass  between   pyramids  through  the  renal  columns     o Arcuate  arteries  branch  from  interlobular  arteries  at  the  boundary  of   the  cortex  and  medulla   o Afferent  arterioles:  microscopic  arterioles  formed  from  branching  of   Arcuate  arteries     § Deliver  blood  into  glomeruli  (capillary  network  that  produce  a   blood  filtrate  that  enters  the  urinary  tubules)   o Efferent  arteriole:  where  remaining  blood  in  the  glomerulus  leaves   through   § Delivers  blood  into  another  capillary  network  –  peritubular   capillaries  surrounding  the  renal  tubules   § This  blood  is  drained  into  veins  that  parallel  the  course  of  the   arteries  in  the  kidney  à  interlobular,  arcuate,  and  interlobar   veins   § Interlobar  veins  leave  kidney  as  a  single  renal  vein  à  empties   into  inferior  vena  cava   o Arrangement  of  blood  vessels  is  unique   § Only  one  in  which  capillary  bed  is  drained  by  an  arteriole   instead  of  a  venule  and  delivered  to  a  second  capillary  bed   downstream   Glomerular  Filtration   • Urine  formation  begins  with  the  filtration  of  plasma  from  glomerular   capillaries  into  Bowman’s  capsule  à  glomerular  filtration  –  results  in   formation  of  filtrate   • Process  utilizes  a  pressure  gradient   • Endothelial  cells  of  the  glomerular  capillaries  have  large  pores  (fenestrae)     o Causes  glomerular  capillaries  to  be  100-­‐400x  more  permeable  to   plasma  water  and  dissolved  solutes  than  skeletal  muscle  capillaries   o Pores  are  still  small  enough  to  prevent  entry  of  RBC,  WBC  and   platelets   • Before  fluid  in  blood  plasma  can  enter  the  interior  of  the  glomerular  capsule,   it  must  pass  through  3  layers  of  selective  filters   o Fluid  entering  is  referred  to  as  filtrate  –  will  become  modified  as  it   passed  through  the  different  segments  of  the  nephron  tubules  to   become  urine   o Capillary  fenestrae  –  first  potential  filtration  barrier   § Large  enough  to  allow  proteins  to  pass  but  are  surrounded  by   charges  that  may  present  some  barriers  to  plasma  proteins   o Glomerular  basement  membrane  –  second  potential  barrier   § Layer  of  collagen  and  proteoglycans  lying  immediately  outside   the  endothelium   § Most  resists  fluid  flow  into  the  capsule  lumen   § Offer  some  barrier  to  plasma  proteins   o Slit  Diaphragm  –  third  potential  barrier   § Visceral  layer  of  glomerular  capsule  is  made  up  of  podocytes   § Unique  epithelial  cells  with  a  bulbous  cell  body,  primary   processes  and  thousands  of  foot  processes   § Processes  are  attached  to  the  basement  membrane   § Narrow  slits  between  adjacent  foot  processes  provide   passageways  for  molecules  entering  the  interior  of  the   glomerular  capsule  as  glomerular  filtrate   § Slit  diaphragm  –  links  interdigitating  foot  processes  and   presents  the  last  potential  filtration  barrier   Forces  Involved  in  Filtration   • Filtration  occurs  due  to  opposing  forces   o Important  elements   § Blood  pressure   § Protein  concentration  in  plasma  compared  to  filtrate  (not   many  proteins  in  filtrate)     • Glomerular  filtration  rate  (GFR)   o Volume  filtered  from  the  glomeruli  into  Bowman’s  capsule  per  unit   time   § Average  ~115-­‐125mL/min   § Consider  average  blood  volume  is  5.5L  à  total  blood  volume  is   filtered  every  40  minutes   • Osmotic  pressure  established  by  presence  of  protein  in  plasma  and  not  really   in  filtrate     o Greater  colloid  osmotic  pressure  of  plasma  promotes  the  osmotic   return  of  filtered  water   o Net  filtration  pressure  of  about  10  mmHg  –  since  glomerular   capillaries  are  extremely  permeable  and  have  a  large  surface  area,  this   modest  filtration  pressure  produces  an  extraordinary  large  volume  of   filtrate   Regulation  of  GFR   • Vasoconstriction  or  vasodilation  of  afferent  arterioles  affects  rate  of  blood   flow  into  glomerulus   • Observe  variety  of  intrinsic  and  extrinsic  mechanisms  to  ensure  GFR  is  high   enough  to  eliminate  wastes  and  regulate  blood  pressure  –  but  not  too  high  as   to  cause  excessive  water  loss   o Sympathetic  nerve  endings   § Vasoconstriction  occurs  in  afferent  arterioles   § Helps  to  preserve  blood  volume  and  divert  blood  to  the   muscles  and  heart   o Renal  auto  regulation   § Observe  relatively  constant  GFR  with  fluctuation  BP   • Afferent  arterioles  dilate  when  BP  falls  below  average   and  constrict  when  BP  is  above  average   • Changes  in  efferent  arterioles  are  of  secondary   importance   § Myogenic  regulation   • Smooth  muscle  of  afferent  arterioles  sensitive  to  stretch   –  result  in  vasoconstriction  when  stretched   § Result  of  effects  of  locally  produced  chemicals  on  the  afferent   arterioles   • Tubuloglomerular  feedback   o Macula  densa:  specialized  cells  that  act  as  the   sensor  –  part  of  a  larger  functional  unit   (Juxtaglomerular  apparatus)     • Increased  delivery  of  NaCl  and  H2O  to  the  distal  tubule   causes  macula  densa  to  release  chemical  signal  causing   constriction  of  the  afferent  arteriole   Renal  Reabsorption   • Most  salt  and  water  filtered  return  to  blood  via  reabsorption     o Defined  as  the  return  of  filtered  molecules  from  the  renal  tubules  to   the  blood   o Proximal  convoluted  tubule  facilitates  reabsorption   • Obligatory  water  loss  –  minimal  volume  needed  to  ensure  excretion  of   metabolic  wastes   o ~400  mL  of  urine  a  day   • Observe  that  transport  of  water  is  passive,  occurring  via  osmosis  à  therefore   a  concentration  gradient  must  be  established  between  filtrate  and  blood  that   favors  osmotic  return   o Filtrate  is  iso-­‐osmotic  to  plasma,  so  we  must  use  interstitial  fluid     o In  some  cases,  active  transport  of  solute  concentrations  is  used  to   facilitate  osmosis     • Process  begins  in  the  epithelial  cells  of  the  proximal  convoluted  tubule   o Epithelial  cells  are  joined  by  apically  located  tight  junctions  –  create   regions  for  exchange   • Sodium  drives  reabsorption   o Sodium  concentration  in  filtrate  and  plasma  are  equal  but  lower  in  the   cytoplasm  of  the  epithelial  cells   § Low  NA+  concentration  due  to  low  permeability  and  Na/K   pump  moving  Na  into  interstitial  fluid   § A  potential  difference  is  created  across  the  proximal  tubule   epithelial  cell  wall  à  electrically  favors  Cl-­‐  movement  from   tubular  fluid  to  interstitial  fluid     o An  increase  in  osmotic  pressure  of  interstitial  fluid  surround  proximal   tubule  cells  creates  an  osmotic  gradient  between  interstitial  fluid  and   tubular  filtrate   o The  proximal  tubule  is  permeable  to  water  so  water  moves  out  by   osmosis   • As  water  moves,  solute  concentration  in  tubular  fluid  increases,  if   mechanisms  in  place  then  solute  moves   o Thus  solutes  follow  solvents  –  explains  how  the  passive  absorption  of   these  solutes  occur   o Also  observe  use  of  Na  gradient  for  co-­‐transport  of  solute   • Transport  maximum  is  limited  –  if  concentration  exceeds  saturation,  there  is   a  loss  of  urine   • Obligatory  water  reabsorption:  water  is  moved  through  osmosis  by  settling   up  sodium  gradient   • Fluid  components  are  kept  Osmotically  balanced  due  to  properties  of  the   renal  tubule   o ~85%  of  original  filtrate  is  reabsorbed  in  early  regions  leaving  ~15%   to  enter  the  distal  convoluted  tubule  and  collecting  ducts   § 15%  x  GFR  of  180L/day  =  27L/day   § This  is  still  an  excessive  amount  so  it  must  be  reabsorbed  to   varying  degrees  to  in  accordance  with  the  needs  of  the  body   § This  is  fixed  by  hormones  that  act  on  the  distal  tubule  and   collecting  duct     Countercurrent  Multiplier  System  and  Countercurrent  Exchange   • For  organism  survival  with  limited  water  intake,  a  mechanism  must  be  in   place  to  produce  a  concentrated  (hyperosmotic)  urine   • Human  kidney  can  produce  a  maximum  urinary  concentration  of   1400mosm/L   o Almost  5x  the  plasma  osmolality   o Occurs  in  medullary  collecting  ducts   § Presence  of  ADH  allows  the  reclaim  of  water   o How  does  the  medullary  interstitial  fluid  become  so  concentration?   § Functions  of  the  loop  of  Henle  in  the  Juxtamedullary  nephrons,   vasa  recta  and  trapping  of  urea  in  kidney  medulla   • Ascending  Limb  of  the  Loop  of  Henle:   o Divided  into  two  regions:     § Thin  segment  near  the  tip  of  the  loop   § Thick  segment  carries  the  filtrate  into  the  distal  convoluted   tubule  in  the  renal  cortex   o NaCl  is  actively  extruded  from  the  thick  segment   § Na  moves  passively  down  its  concentration  gradient  from  the   filtrate  into  the  cells  à  powers  inward  secondary  active   transport  of  K+  and  Cl-­‐   § Na  is  then  transported  into  the  interstitial  fluid  via  the  Na/K   pump   • Cl-­‐  passively  follows  the  Na+  due  to  the  electrical   attraction   • K+  passively  diffuses  back  into  the  filtrate   o The  ascending  limb  is  not  permeable  to  water  so  water  cannot  follow   the  flow  of  salt  as  seen  in  the  proximal  tubule  à  by  the  time  the   filtrate  reaches  the  distal  tubule  the  filtrate  is  very  dilute  and  the   interstitial  fluid  is  hypertonic  to  it     • Descending  Limb  of  the  Loop  of  Henle   o Does  not  actively  transport  salt  and  is  impermeable  to  the  passive   transport  of  it   o Unlike  the  ascending  limb,  the  descending  limb  is  permeable  to  water   § Allows  it  to  release  water  Osmotically     § Increases  the  salt  concentration  arriving  in  the  ascending  limb   à  increases  salt  transport  by  the  ascending  limb  so  that  the   NaCl  concentration  of  the  interstitial  fluid  is  multiplied   • Countercurrent  Multiplication   o Positive  feedback  mechanism  is  created  by  the  interactions  of  the   proximal  and  distal  tubule  effecting  the  concentrations  of  filtrate  and   interstitial  fluid   § The  more  salt  extruded  by  the  ascending  limb,  the  more   concentrated  the  fluid  that  is  delivered  to  it  from  the   descending  limb  will  be   § Positive  feedback  mechanism  that  multiplies  the  concentration   of  the  interstitial  fluid  and  descending  limb  fluid  is  called  the   countercurrent  multiplier  system   • Steps  of  the  mechanism:  Start  with  isosmotic  fluid  leaving  descending  and   reaching  ascending  à  NaCl  is  pumped  out  actively  à  NaCl  trapped  in   interstitial  fluid  by  vasa  recta  (blood  vessels)   o NaCl  pumped  out  of  ascending  limb  causes  interstitial  fluid  to  be   hypertonic   o The  hypertonic  interstitial  fluid  causes  the  descending  limb  to  release   water  through  osmosis  à  causes  filtrate  to  be  somewhat  hypertonic   when  it  reaches  back  to  the  ascending  limb   o The  now  higher  NaCl  concentration  in  the  ascending  limb  allows  it  to   pump  out  more  NaCl  than  it  did  before  because  more  NaCl  is  available   to  carriers  à  causes  interstitial  fluid  to  become  even  more   concentrated   o The  increased  concentration  of  interstitial  fluid  causes  even  more   water  to  be  drawl  out  of  the  descending  limb  à  causes  filtrate  to  be   even  more  hypertonic  when  it  reaches  back  to  the  ascending  limb   o The  progression  repeats  to  a  higher  extend  each  time  until  the   maximum  concentration  is  reached  in  the  inner  medulla  –  the   maximum  value  is  determined  by  the  capacity  of  the  active  transport   pumps  working  along  the  lengths  of  the  thick  segments  of  the   ascending  limbs   • What  does  the  countercurrent  multiplier  accomplish?   o Increases  concentration  of  renal  interstitial  fluid  from  300  mOsm  in   the  cortex  to  1200  mOsm  in  the  inner  medulla  –  the  hypertonicity  of   the  renal  medulla  is  critical  because  it  serves  as  the  driving  force  of   water  reabsorption  through  the  collecting  ducts   • Vasa  recta:     o Vessels  that  parallel  the  nephron  loop   o Have  urea  transporters  and  aquaporins  in  the  plasma  membrane   § Allows  for  them  to  gain  salt  and  urea  and  lose  water     o Countercurrent  exchange:  mechanism  allowing  vasa  recta  to  maintain   hypertonicity   § Salt  and  other  dissolved  solutes  found  in  high  concentration  in   the  interstitial  fluid  diffuse  into  descending  vasa  recta   § The  same  solutes  passively  diffuse  out  of  the  ascending  vasa   recta  and  back  into  the  interstitial  fluid  à  completes   countercurrent  exchange   § This  constant  circulation  allows  for  the  solute  to  be  trapped  in   the  medulla   o Net  action  of  the  vasa  recta  is  to  remove  water  from  the  interstitial   fluid  of  the  renal  medulla     Effects  of  Urea   § Urea  functions  as  an  osmotically  active  molecule   o Trapped  within  the  medullary  interstitial  fluid  because  of  constant   recycling  –  supports  this  regions  high  osmolality   § Presence  of  NaCl  and  urea  make  interstitial  fluid  very  hypertonic,  creating  an   environment  so  that  water  can  leave  via  osmosis  from  the  collecting  ducts   Collecting  Duct  and  ADH:   § The  collecting  duct  is  impermeable  to  NaCl  but  has  aquaporins  allowing   water  to  flow     § Since  the  interstitial  fluid  is  hypertonic,  water  flows  out  of  the  collecting  duct   via  osmosis   o The  water  does  not  dilute  the  surrounding  interstitial  fluid  because  it   is  transported  back  to  general  circulation  in  the  vascular  system   § The  force  driving  osmosis  is  created  by  the  countercurrent  multiplier  system   o Concentration  gradient  is  thus  kept  relatively  constant  but  can  change   based  on  variations  in  permeability  to  water  made  by  regulating  the   number  of  aquaporins   § Aquaporins  –  water  channels  in  the  plasma  membrane  of  the   collecting  duct  epithelial  cells   § When  plasma  osmolality  increases  by  as  little  as  1%,  the  anterior  pituitary   secretes  arginine  vasopressin  –  functions  as  antidiuretic  hormone  (ADH)   o In  response,  cAMP  is  produced  and  after  a  series  of  reactions  inserts   aquaporins  on  the  plasma  membrane     o Increased  number  of  aquaporins  increases  the  collecting  ducts   permeability  to  water  and  allows  for  increased  water  reabsorption  à   facultative  water  reabsorption   o Decreased  release  of  ADH  decreases  the  number  of  aquaporins  in  the   membrane,  decreasing  water  permeability,  decreasing  water   reabsorption  and  causing  for  more  dilute  urine  excretion  in  larger   volumes   § ADH  release  is  stimulated  by  Osmoreceptors  in  the  hypothalamus  due  to   change  in  blood  plasma  osmolality   § In  cases  of  extreme  dehydration  increasing  amounts  of  ADH  will  be  released   o Urine  excretion  will  decrease  until  it  reaches  the  obligatory  water  loss   ~400  mL/day   o Decrease  in  urine  excretion  is  limited  to  this  value  because  urine   cannot  become  more  concentrated  than  the  interstitial  fluid   § Note:  even  in  the  complete  absence  of  ADH  some  water  will  still  be   reabsorbed  through  the  collecting  ducts   Renal  Plasma  Clearance   § Renal  clearance  –  ability  of  kidneys  to  remove  molecules  from  blood  plasma   by  excreting  urine  –  “clearing”  blood  of  particular  solutes   o Clearing  occurs  due  to  glomerular  filtration  and  tubular  secretion   o Reabsorption  decreases  renal  clearance   § Excretion  rate  =  (filtrate  rate  +  secretion  rate)  –  reabsorption  rate   o After  filtration,  if  a  solute  is  neither  secreted  or  reabsorbed,  the   excretion  rate  =  filtration  rate   o Under  that  assumption,  the  glomerular  filtration  rate  can  be   determined  and  used  to  assess  the  health  of  the  kidneys   § Glomerular  filtration  rate  =  volume  of  blood  plasma  filtered   per  minute   § While  most  substances  produced  in  the  body  are  always  either  secreted  or   reabsorbed,  insulin  is  not  à  rate  of  insulin  filtration  is  exactly  equal  to  rate   of  excretion  of  it     o GFR  =  (V  x  U)  /  P   § V  =  rate  of  urine  formation   § U  =  concentration  of  substance  in  urine   § P  =  concentration  of  substance  in  plasma   § Renal  plasma  clearance  is  the  volume  of  plasma  from  which  a  substance  is   completely  removed  in  one  minute  by  excretion  in  the  urine   o When  the  substance  is  neither  reabsorbed  nor  secreted,  GFR  =  renal   plasma  clearance   o Renal  plasma  clearance  =  GFR  =  (VU)/P   o If  a  solute  is  reabsorbed,  the  renal  plasma  clearance  of  a  substance   must  be  less  than  the  GFR   o If  a  solute  is  secreted,  the  renal  plasma  clearance  will  be  less  than  the   GFR   § Glucose  and  amino  acids  are  easily  filtered  from  blood  through  Bowman’s   capsule  but  are  not  found  in  excreted  urine  à  indicates  they  must  be   completely  reabsorbed   o Reabsorption  of  these  occurs  on  the  proximal  convoluted  tubule  via   secondary  active  transport  of  carrier  proteins     o Carrier  proteins  exhibit  property  of  saturation   § One  carrier  =  1  molecule  at  a  take   § Transport  maximum:  exists  when  the  transported  molecule  is   present  in  such  high  concentrations  that  all  carrier  proteins  are   occupied  and  the  transport  rate  reaches  a  maximum     Renal  Control  of  Electrolytes     § Kidneys  assist  with  regulation  of  several  electrolytes  by  matching  urinary   excretion  with  dietary  intake   o 90%  of  filtered  Na  and  K  are  reabsorbed  by  the  proximal  convoluted   tubule     § Occurs  at  a  constant  rate   § Not  subjected  to  hormonal  regulation  but  in  regard  to  body   needs   § Role  of  aldosterone  in  Na  and  K  balance  –  modifies     o Regulation  can  occur  via  the  mineralocorticoid  aldosterone   § Na  reabsorption     • Excrete  ~30mg  a  day  in  urine   • Na  concentration  can  diminish  to  0  in  the  presence  of   aldosterone   • Induces  synthesis  of  all  channels  and  pumps  in   collecting  duct   § Filtration  relies  on  blood  pressure  and  radius  of  afferent/efferent  arteriole   § Potassium  secretion     o Occurs  in  distal  convoluted  tubule  and  collecting  ducts   § Aldosterone-­‐dependent  potassium  secretion     • Potassium  rich  mean  increases  blood  potassium  and   stimulated  adrenal  cortex  to  release  aldosterone  –   results  in  potassium  secretion  into  filtrate   § Also  can  occur  via  aldosterone-­‐independent  potassium   secretion   • Potassium  rich  meal  causes  insertion  of  potassium   channels  into  plasma  membrane  of  cortical  collecting   duct  cells  due  to  concurrent  elevation  in  blood   potassium  concentration     o Another  mechanism  –  sensory:   § With  increased  sodium  due  to  increase  flow  in  filtrate,  it  is   “sensed”  by  a  primary  cilium   § So  as  flow  “bends”  the  cilium  it  activated  potassium  channels   leading  to  increased  potassium  secretion   § Explains  how  some  diuretics  can  cause  low  blood  potassium   levels   Control  of  aldosterone  secretion     § Aldosterone  promotes  Na  retention  and  K  secretion  –  thus  with  a  rise  in   blood  K  levels  aldosterone  secretion  is  increased  (direct  mechanism)   § However,  with  Na  the  process  is  more  complex  and  typically  involves  a  fall  in   blood  volume  along  with  activation  of  the  renin-­‐angiotensin-­‐aldosterone   system  (indirect  mechanism)   Atrial  Natriuretic  Peptide     § With  an  increased  blood  volume,  observe  salt  secretion  and  water  loss  which   is  due  in  part  to  inhibition  of  aldosterone  release   § However,  natriuretic  peptides  are  involved  in  long-­‐term  Na  and  water   balance  (also  blood  volume  and  pressure)   o Natriuretic  peptides  –  serve  as  a  counter-­‐regulatory  system  for  the   renin-­‐angiotensin-­‐aldosterone  system   § Produces  in  cells  in  the  atria  and  other  areas  such  as  the  brain   § Cause  an  increase  in  GFR   § Produces:   • Natriuesis  –  increased  sodium  excretion   • Diuresis  –  increased  fluid  in  excretion   § K  sparing:  since  Na  is  secreted,  spare  K  will  be  taken  up   Relationship  Between  Na,  K  and  H   § Blood  K  concentration  indirectly  affects  blood  H  concentration   § Observe  that  as  extracellular  H+  concentration  increases  in  the  collecting   duct,  some  H+  moves  into  the  cell  and  causes  cellular  K  to  diffuse  outward   into  extracellular  fluid   o Reestablishes  proper  ratio  of  these  ions  in  extracellular  fluid  with   same  occurring  in  distal  convoluted  tubule  cells   § As  Na  moves,  K  and  or  H  are  secreted  to  maintain  charge  balance   o In  acidosis  –  observe  an  increase  in  blood  K  concentration  (not   secreted)     o In  alkalosis  –  observe  a  decrease  in  blood  K  concentration  (secreted)   o Hyperkalemia  (too  much  K  in  blood)  leads  to  acidosis  because  when  K   is  secreted,  H  is  retained   Renal  Acid-­‐Base  Regulation     § Kidneys  assist  with  blood  pH  regulation  by  excreting  H+  and  reabsorbing   bicarbonate   § H+  enters  filtrate  by  glomerular  filtration  and  secretion  into  renal  tubules  à   the  acidification  of  urine   § Tubule  cells  are  impermeable  to  bicarbonate  so  its  absorption  is  indirect   § During  acidosis,  proximal  convoluted  tubule  can  make  more  bicarbonate  via   glutamine  metabolism     o Bicarbonate  goes  into  blood  and  formed  NH3  buffers  urine   § During  alkalosis,  less  bicarbonate  is  reabsorbed  due  to  less  H  in  filtrate   o Excretion  assists  with  compensation  for  alkalotic  condition     Urinary  Buffers   § As  blood  pH  falls  below  7.35,  urine  pH  typically  falls  below  5.5   o Note  that  the  nephron  cannot  produce  a  urine  below  4.5   o To  excrete  more  H+  it  must  be  buffered   § Bicarbonate  cannot  accomplish  this  because  it  is  mostly   reabsorbed   § Alternatives:  phosphates  and  ammonia    


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