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Anatomy,  Physiology  &  Homeostasis • Anatomy:  study  of  form   • Physiology:  study  of  func:on   – In  essence,  human  physiology  is  the  study  of  how   the  body  perceives  and  achieves  homeostasis

Homeostasis • The  regula:on  of  the  body’s  fluid  environment   within  a  specific  range  of  values,  or  around  a   set  point

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Fluid  Environment • Human  body  is  ~70%   water,  by  weight   • Human  cells  are  ~70%   water,  by  volume   • Homeostasis  involves   regula:ng  this  water,  and   this  is  physiology

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Nega:ve  Feedback • Homeostasis  is   generally  achieved   using  nega:ve   feedback   mechanisms   • “Devia:on  from  a  set   point  is  resisted”   – If  the  variable  is  too   high,  we  act  to  lower   it   – If  the  variable  is  too   low,  we  act  to  raise  it

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Nega:ve  Feedback • Nega:ve  feedback  loops  require   – Receptor  (to  sense  s:mulus)   – Control  center  (to  compare  s:mulus  to  set  point)   – Effector  (to  change  the  value  of  the  s:mulus   variable)

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Nega:ve  Feedback  –  Example • Baroreflex:  primary  determinant  of  blood   pressure   • Iden:fy?   – Receptors   – Control  center   – Effector

Nega:ve  Feedback  –  Example

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Nega:ve  Feedback  –  Example

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Posi:ve  Feedback  Loops • If  variable  is   increasing,  the   body  acts  to   increase  it  more   • Requires  a   mechanism  to   break  the  loop

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Posi:ve  Feedback  Loops • Uterine  labor   – Receptor:  stretch  receptors  in  cervix   – Control  center:  hypothalamus  and  posterior   pituitary  gland  (secretes  oxytocin=OT)   – Effectors:  muscular  wall  of  uterus  (lots  of  oxytocin   receptors)   – Mechanism  to  break  loop:  a^er  birth,  stretch   receptors  no  longer  s:mulated

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Posi:ve  Feedback  Loops • Breast  feeding   – Receptor:  mechanoreceptors  in  nipple   – Control  center:  hypothalamus  and  posterior   pituitary  gland  (secretes  oxytocin)   – Effectors:  myoepithelial  cells  surrounding  milk  sacs   – Mechanism  to  break  loop:  mechanoreceptor   s:mula:on  ceases

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Regula:on  of  Blood  Gases • Blood  gases  of  interest:  oxygen,  carbon  dioxide   • How  do  we  regulate  these?

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Regula:on  of  Blood  Gases • Most  important  equa:on  in  this  course!  

CO2  +  H2O   HCO3-­‐  +  H+

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Regula:on  of  Blood  Gases • • • •

pH  =  –log[H+]   Range:  0-­‐14   pH  7=pure  water  (neutral)   Log  scale,  so  a  pH  change  of  1,  reflects  a  10-­‐ fold  change  in  hydrogen  ions  (acidity)   • As  hydrogen  ions  increase,  pH  goes  down

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Regula:on  of  Blood  Gases

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Regula:on  of  Blood  Gases • H+  =  an  acid   • Defini:on  of  acid:  anything  that  gives  up  H+  in   water   • Strong  acids  (HCl)  disassociate  into  separate   ions  (H+and  Cl-­‐  more  readily  in  water)   • Where  are  acids  produced?  And  how?

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Regula:on  of  Blood  Gases • HCO3-­‐  =  a  base  (bicarbonate  ion)   • Bases  can  collect  extra  H+  to  increase  pH   • Can  use  the  equa:on  to  alter  pH,  and  to   produce  hydrogen  and  bicarbonate  ions   • Where  is  bicarbonate  produced?

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Regula:on  of  Blood  Gases  –  CO2 • CO2  levels  in  blood  drive  breathing  rate  and   depth   • Small  changes  in  CO2  levels  result  in  rapid   responses  of  changes  in  breathing   • Body  uses  breathing  to  eliminate  extra  CO2   and  to  restore  acid-­‐base  balance

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Regula:on  of  Blood  Gases  –  CO2

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Regula:on  of  Blood  Gases  –  CO2

Regula:on  of  Blood  Gases  –  O2

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• Although  oxygen  intake  is  a  necessary  part  of   respira:on,  O2  levels  don’t  drive  respira:on   the  same  way  CO2  levels  do   • Human  body  is  rela:vely  unresponsive  to  O2   changes  un:l  O2  levels  are  seriously   compromised

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Regula:on  of  Acid-­‐Base  Balance • CO2  +  H2O    HCO3-­‐  +  H+   • Regula:ng  CO2  is  regula:ng  pH   • Elimina:ng  CO2  drives  equa:on  to  the  le^,   reducing  free  hydrogen  ions,  and  raising  pH

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Regula:on  of  Acid-­‐Base  Balance

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Regula:on  of  Nutrients • Macronutrients  =  sugars,  fats,  proteins   • Glucose  regula:on  is  regulated  by  insulin  and   glucagon  nega:ve  feedback  loop   – As  blood  sugar  increases,  the  body  acts  to  decrease   it  (insulin)   – As  blood  sugar  decreases,  the  body  acts  to  increase   it  (glucagon)

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Regula:on  of  Glucose • Pancreas  directly  evaluates  blood  sugar  levels,  when   glucose  levels  are  too  high,  the  beta  cells  in  the   pancreas  secrete  insulin  (hormone)   • Insulin  binds  to  insulin  receptors  (on  virtually  all  body   cells)   • Insulin  receptors  tell  cell  to  increase  ac:vity  and   number  of  glucose  carriers,  resul:ng  in  increased   uptake  of  glucose  into  cells   • Result:  blood  glucose  drops

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Regula:on  of  Glucose • When  glucose  levels  are  too  low,  the  alpha  cells  in   the  pancreas  secrete  glucagon  (another  hormone)   • Glucagon  travels  to  areas  of  stored  carbohydrates   • Glucagon  ac:vates  an  enzyme  that  s:mulates   glycogenolysis  (chains  of  mostly  glucose  molecules)   • Result:  blood  glucose  increases

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Regula:on  of  Glucose

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Regula:on  of  Glucose

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Regula:on  of  Glucose • Blood  sugar  levels  are  constantly  increasing   and  decreasing   – Without  meal,  insulin  secreted  every  ~20  min   – Meals  result  in  a  large  blood  sugar  increase,  and   thus  a  large  increase  in  insulin  secre:on,  followed   by  a  hypoglycemic  rebound  

• For  what  part  of  the  body  is  blood  sugar   regula:on  most  important?

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Regula:on  of  Fats  (Lipids) • Most  common  storage  lipid=triglyceride  [TG]   (glycerol  molecule  +  3  faly  acid  [FA]  chains)   • Lots  of  energy  is  stored  in  each  FA/TG   • TG  is  unwieldy,  so  when  the  body  needs  to   access  energy,  it  breaks  off  the  FA  chains

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Regula:on  of  Fats  (Lipids) • The  rate  that  the  body  converts  TG  into  free  FA   chains  using  adipose  lipase  =  the  rate  that  FA   becomes  available  for  use   • What  causes  us  to  break  TG  into  FA?

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Regula:on  of  Fats  (Lipids) • Factors  that  increase  TG  breakdown  to  FA   – Low  insulin  levels  (and  therefore  low  glucose)   – Epinephrine/norepinephrine  (increase  with  stress   and/or  exercise)   – Growth  hormone   – Thyroid  hormone

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Appe:te  Regula:on • Hunger  center   – Hypothalamus  (hunger/sa:ety  centers)   – Major  regulator  of  appe:te  in  most  animals  

• What  else  influences  our  hunger?  what  we   eat?  how  much  we  eat?

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Appe:te  Regula:on • Lep:n  

Guess which mouse doesn’t make leptin?

– Released  from  from  adipose  cells  when  they  are   full,  reducing  appe:te   – As  adipose  cells  shrink  (because  TGs  are  being   converted  to  FA  and  used),  the  lep:n  release   decreases,  s:mula:ng  appe:te   – Many  obese  people  are  lep:n-­‐resistant,  but  have   high  levels  of  lep:n  (receptor  deficit)

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Regula:on  of  Ion  Concentra:on • Cells  use  ion  concentra:ons  as  a  major   mechanism  of  direc:ng  cell  ac:vity   • Sodium  (Na+)  and  potassium  (K+)  ions  are   balanced  by  kidney  (covered  in  more  detail  in   A&P  I)   • All  cells,  but  especially  neurons,  work  because   of  appropriate  ion  amounts  inside  and  outside   cell

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Regula:on  of  Ion  Concentra:on • Na+  levels  higher  outside  the  cell   • K+  levels  higher  inside  the  cell,  but  intracellular   environment  has  a  net  nega:ve  charge

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Regula:on  of  Ion  Concentra:on • Muscle  cell  –  example   – When  s:mulated,  Na+  channels  open,  allowing  Na+   to  rush  in,  the  cell  becomes  posi:vely  charged  and   the  voltage  change  results  in  muscle  contrac:on   – To  reset  the  internal  nega:ve  charge,  K+  flows  out   of  the  cell  through  channels   – What  happens  if  there  is  a  high  [K+]  outside  the   cell?

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Regula:on  of  Ion  Concentra:on • Muscle  cell  –  example   – Excessive  [K+]  concentra:ons  in  the  extracellular   fluid  (ECF)  result  in  cell’s  inability  to  reset  and   contract  again   – K+  levels  evaluated  by  receptors  on  the  adrenal   cortex   – Response:  aldosterone  secre:on  by  adrenal  glands

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Regula:on  of  Ion  Concentra:on

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Regula:on  of  Blood  Volume • Water  exists  in   three   compartments   – Intracellular   – Inters::al   (extracellular   fluid=ECF)   – Blood

Regula:on  of  Blood  Volume

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• What  is  the  “normal”  amount  of  blood?   • Where  does  fluid  come  from/go  to?

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Regula:on  of  Blood  Volume • What  are  blood  flow  des:na:on  priori:es?   – BRAIN  (nearly  constant)   – Heart  (varies  –  why?)   – Either  (depending  on  demands)   • Muscles  and  skin   • Guts,  kidneys,  liver,  etc.

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Regula:on  of  Low  Blood  Volume • Decreased  blood  volume   – Receptor:  osmoreceptors  sense  high  osmolarity   (solute  [salt]  concentra:on)  in  ECF   – Control  center:  hypothalamus   – Effectors:   • Thirst  center  neurons  create  thirst   • An:diure:c  hormone  (ADH)  secre:ng  cells  of  posterior   pituitary  act  on  kidney  to  conserve  water  in  urine

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Regula:on  of  Blood  Volume

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Regula:on  of  Blood  Volume

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Regula:on  of  High  Blood  Volume • Increased  blood  volume   – Receptor:  stretch  receptor  in   atrium   – Atrial  myocytes  secrete  ANF   (atrial  natriure:c  factor  or   pep:de)   – Effectors:  in  response  to  ANF,   kidneys  excrete  more  Na+  and   water  follows,  resul:ng  in   decreased  blood  volume

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Regula:on  of  Water  Temperature • Directed  by  autonomic  nervous  system   (sympathe:c  vs.  parasympathe:c)   • Too  warm?  Direct  blood  to  skin  (dila:ng  skin   arterioles)  while  restric:ng  blood  to  the  guts   and  viscera  [sympathe:c]   • Too  cold?  Shunt  blood  to  body  core,   constric:ng  the  vessels  to  the  skin   [parasympathe:c]

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Regula:on  of  Water  Temperature

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Cancer • Devia:on  from  homeostasis:  disrup:on  in  the   number  of  and  behavior  of  cells   • Overall  life:me  risk  of  cancer  diagnosis  in  US  (ACS):   – 50%  for  men   – 33%  for  women  

• Overall  life:me  risk  of  cancer  death  in  US  (NCI):   – 23%  for  men   – 20%  for  women

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Cancer • In  homeostasis,  the  growth  rate  of  cells  equals  the   death  rate  (even  replacement)   • Cancer:  abnormal  net  growth  rate  of  :ssue  and   abnormal  behavior  of  cells   – Cells  stop  dying  off  and/or  reproduce  too  quickly   – Cells  stop  differen:a:ng  and  acquire  ability  to  metastasize   – All  these  changes  accumulate  to  malignant  cancer

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Cancer

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Characteris:cs  of  Cancer  Cells • • • • •

Lose  contact  inhibi:on   Live  longer  than  most  cells   Undifferen:ated   High  metabolic  rate   All  of  these  characteris:cs   are  the  result  of   accumulated  muta:ons

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Cancer  &  Gene:cs • All  cancers  are  “gene:c”   – Cancer  (abnormal  and  uncontrolled  cell  growth)  is   due  to  a  series  of  muta:ons  in  DNA  

• Not  all  cancer  is  “hereditary”   – Most  gene:c  muta:ons  that  lead  to  cancer  are   acquired  over  a  person’s  life:me   – Roughly  5%  of  cancer  death  is  alributable  to   inherited  gene:c  muta:ons  that  predispose  a   person  to  a  par:cular  type  of  cancer

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Cancer  Progression • Cancer  is  usually  the  result  of   the  accumula:on  of  mul:ple   muta:ons,  and  the   progression  of  disease  process   • Finding  cancer  early  (benign)   or  before  much  metastasis   results  in  beler  outcome

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Cancer  Progression

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Cancer  Progression • Preven)on  easier,  more  effec)ve,  and  less   expensive  than  treatment   – Primary  preven:on  (prevent  cancer  from  occurring)   – Secondary  preven:on  (early  diagnosis  and   treatment)   – Tools  for  preven:on?  Screening/early  detec:on?

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• Carcinogens  cause  muta)ons   • Cancer  typically  mul)factorial:   – – – –

gene)c  predisposi)on   toxic  chemicals   infec)on  (HPV,  H.  pylori)   physical  factors  (trauma,  radia)on)

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Alributable  Causes  of  Cancer  Death

Source: Harvard Center for Cancer Prevention. Harvard Report on Cancer Prevention. 1996.

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Mechanisms  of  carcinogenesis • Turning  on   dormant  oncogene   • Conversion  of   proto-­‐oncogene  to   oncogene   • Turning  off  tumor
 suppressor  gene
 (TSG)