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Human Physiology Chapter 18 Notes

by: MBattito

Human Physiology Chapter 18 Notes BIOL 3160

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These notes cover material from chapter 18 from lecture, the power points and the textbook
Human Physiology
Dr. Tamara McNutt-Scott
Class Notes
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This 13 page Class Notes was uploaded by MBattito on Thursday April 21, 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 6 views. For similar materials see Human Physiology in Biological Sciences at Clemson University.


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Date Created: 04/21/16
Chapter  18:  The  Digestive  System     Digestive  System   • Organs  of  this  system  function  to  procure  food,  process  it  and  eliminate   generated  wastes   o Involves  the  processes  of  ingestion,  digestion  and  absorption  and   waste  removal   • Without  this  system  the  body  would  be  unable  to  obtain  needed  materials  for   fuel  generation  and  cell  maintenance   • Overlooked  point:  absorbed  nutrients  from  GI  tract  also  use  for  structural   elements   Functions  of  the  Digestive  System:   • Motility:  movement  of  food  through  the  digestive  tract  via   o Ingestion  –  taking  food  into  mouth   o Mastication  –  chewing  the  food  and  mixing  it  with  saliva   o Deglutination  –  swallowing  food   o Peristalsis  and  Segmentation–  rhythmic  wave-­‐like  contractions   (peristalsis)  and  mixing  contractions  in  different  segments   (segmentation)  move  food  through  the  GI  tract   • Secretion:  exocrine  and  endocrine  secretions   o Exocrine:  water,  HCl,  bicarbonate,  and  digestive  enzymes  are  secreted   into  the  lumen  of  the  GI  tract   § Stomach  alone  secretes  2-­‐3  intestine  secrete  hormones  to   regulate  digestive  system   • Digestion:  breakdown  of  food  molecules  into  their  smaller  subunits,  which   can  be  absorbed   • Absorption:  passage  of  digested  end  products  into  the  blood  and  lymph   • Storage  and  elimination:  temporary  storage  and  subsequent  elimination  of   indigestible  food  molecules   • Immune  barrier:     o Tight  junctions  between  epithelial  cells  provide  a  physical  barrier   o Cells  of  the  immune  system  reside  in  the  connective  tissue  located   under  the  epithelium     Digestive  system  can  be  divided  functionally  and  anatomically   • Gastrointestinal  tract:   o Oral  cavity   o Pharynx   o Esophagus   o Stomach   o Small  intestine   o Large  intestine   • Accessory  digestive  organs:   o Pancreas   o Liver   o Gallbladder     o Teeth   o Tongue   o Salivary  glands   GI  Tract  Wall  (from  the  inside  out)   • Mucosa:  lines  the  lumen   o Absorptive  and  major  secretory  layer   o Consists  of  simple  columnar  epithelium  supported  by  the  lamina   propria     § Lamina  propria  –  thin  layer  of  areolar  connective  tissue  with   numerous  lymph  nodules  à  immune  defense   o Muscularis  mucosa:  thin  layer  of  smooth  muscle  external  to  lamina   propria   § Responsible  for  numerous  folds  à  increases  surface  area  for   maximum  absorption   o Goblet  cells:  specialized  cells  that  secrete  mucus     • Submucosa:  highly  vascular  layer  of  connective  tissue   o Absorbed  molecules  in  mucosa  enter  into  these  blood  and  lymph   vessels   o Contains  glands  and  nerve  plexuses   § Submucosal  plexus:  aka  Meissner’s  Plexus  –  provides  a  nerve   supply  to  the  Muscularis  mucosae  of  the  small  and  large   intestine   • Muscularis:  responsible  for  the  peristalsis  and  segmentation   o Inner  circular  and  outer  longitudinal  layer  of  smooth  muscle     o Myenteric  plexus:  located  between  the  two  muscle  layers  –  provides   the  major  nerve  supply  to  the  entire  GI  tract   § Includes  fibers  and  ganglia  from  both  the  sympathetic  and   parasympathetic  divisions  of  the  autonomic  nervous  system   • Serosa:  completes  the  GI  tract  wall   o Areolar  connective  tissue  covered  with  a  layer  of  simple  squamous   epithelium     o Continuous  with  the  mesentery  and  visceral  peritoneum   Regulation  of  GI  Tract   • Parasympathetic  nerves  stimulate  motility  and  secretions  of  the  GI  tract   o Sympathetic  nerves  stimulate  contraction  of  sphincter  muscles  and   decrease  peristalsis  and  secretions  à  antagonistic  to  parasympathetic     • Submucosal  and  myenteric  nerve  plexuses  are  sites  where  parasympathetic   preganglionic  fibers  synapse  with  postganglionic  neurons  that  innervate  the   smooth  muscle  of  the  GI  tract   • Autonomic  nervous  and  endocrine  systems  regulates  GI  tract  extrinsically     • Enteric  system  and  paracrine  regulators  regulate  it  intrinsically   o Intrinsic  sensory  neurons  have  their  cell  bodies  within  the  gut  wall  –   locally  regulate  digestive  tract  by  enteric  nervous  system  (complex   neural  network  within  the  wall  of  the  gut)       Digestive  Tract  Physiology   • Process  begins  with  ingestion  of  foodstuffs  and  mastication  (chewing)  à   chewing  mechanically  digests  food  but  also  mixes  it  with  saliva  containing   salivary  amylase  (carbohydrate  digestion)   From  Mouth  to  Stomach   • Overall:  peristaltic  contractions  of  the  esophagus  deliver  food  to  the  stomach,   which  secretes  very  acidic  gastric  juice  that  is  mixed  with  the  food  by  gastric   contractions  –  proteins  in  the  resulting  mixture  (called  chyme)  are  partially   digested  by  the  enzyme  pepsin   • Deglutination  –  swallowing,  following  mastication   o Three  phases:  oral,  pharyngeal  and  esophageal   § Oral  phase  is  under  voluntary  control  via  somatic  motor   neurons   • Muscles  in  the  mouth  and  tongue  mix  the  food  with   saliva  and  create  a  bolus  –  the  mass  to  be  swallowed  –   that  the  tongue  moves  toward  the  oropharynx     • Receptors  in  the  oral  cavity  and  oropharynx  stimulate   the  pharyngeal  phase   § Pharyngeal  and  esophageal  phases  are  automatic  and   controlled  by  the  swallowing  center  in  the  brain  stem  via   autonomic  neurons     • Pharyngeal  phase  moves  the  bolus  from  the  oral  cavity   to  the  esophagus   • Complex  activities  in  the  pharyngeal  phase:  soft  palate   lifts  to  close  off  nasopharynx  (so  food  does  not  go  into   nose),  vocal  cords  close  off  the  opening  to  the  larynx,   epiglottis  covers  the  vocal  cords,  larynx  is  moved  away   from  the  pathway  of  the  bolus  toward  the  esophagus   (prevents  choking)   o All  activities  only  take  a  total  of    ~1  second   • Esophageal  phase  moves  the  bolus  of  food  by  peristaltic   contractions  toward  the  stomach   o ~5-­‐6  seconds   • Once  in  the  stomach,  ingested  material  is  churned  and  mixed  with  HCl  and   pepsin  (protein  digesting  enzyme)   o Mixture  is  pushed  via  muscular  contractions  past  the  pyloric   sphincter     § Pyloric  sphincter  guards  entry  of  small  intestine  from  stomach   Esophagus     • Portion  of  the  GI  tract  that  connects  the  pharynx  to  the  stomach   • Esophageal  hiatus  –  opening  in  the  diaphragm  allowing  the  esophagus  to   pass  through  before  entry  into  the  stomach   • Walls  of  esophagus  contain  either  skeletal  or  smooth  muscle   o Upper  portion  is  only  skeletal  muscle   o Middle  portion  is  skeletal  and  smooth  muscle   o Lower  portion  is  only  smooth  muscle   • Gastroesophageal  sphincter  –  slightly  narrow  terminal  portion  of  the   esophagus  at  the  entrance  to  the  stomach  due  to  thickening  of  the  circular   muscle  fibers  in  its  wall   o Sphincter  contracts  after  bolus  enters  stomach  to  prevent   regurgitation     o Not  a  true  sphincter  in  humans,  allowing  us  to  regurgitate     o Heartburn  is  produced  if  stomach  acid  reaches  the  esophagus     Stomach   • Most  distensible  part  of  the  GI  tract   • Functions:  store  food,  initiate  digestion  of  proteins,  to  kill  bacteria  with  the   strong  acidity  of  the  gastric  juice  and  to  move  the  food  into  the  small   intestine  as  a  pasty  material  called  chyme   • Contractions  of  the  stomach  churn  the  chyme  –  mixes  it  more  thoroughly   with  the  gastric  secretions   o These  contractions  also  push  partially  digested  food  from  the  antrum   through  the  pyloric  sphincter  and  into  the  first  part  of  the  small   intestine   • Rugae:  long  folds  on  the  inner  surface  of  the  stomach   • Gastric  pits:  openings  of  these  folds  into  the  stomach  lumen   • Exocrine  gastric  glands:  formed  by  cells  that  line  the  folds  –  secrete  various   products  into  the  stomach   o Mucous  neck  cells:  secrete  mucus   o Parietal  cells:  secrete  HCl   § Used  in  small  intestine  for  absorption  of  vitamin  B12   o Chief  cells:  secrete  pepsinogen  (inactive  form  of  pepsin)   o ECL  cells:  secrete  histamine  and  serotonin  à  paracrine  regulators   o G  cells:  secrete  the  hormone  gastrin  into  the  blood   o D  cells:  secrete  the  hormone  somatostatin   • Intrinsic  factor:  polypeptide  secreted  by  the  gastric  mucosa  required  for   intestinal  absorption  of  Vitamin  B12   o Vitamin  B12  is  necessary  for  the  production  of  red  blood  cells  in  the   bone  marrow   • Ghrelin:  hormone  secreted  by  the  stomach   o Secretion  rises  before  meals  and  falls  after  –  serves  as  a  signal  from   the  stomach  to  the  brain  to  regulate  hunger   • Gastric  juice:  highly  acidic  solution  formed  by  a  large  amount  of  water  and   the  exocrine  secretions  of  the  gastric  cells   • Enteroendocrine  cells:  individual  cells  that  produce  hormones  like  gastrin   Secretion  of  Acid  in  the  Stomach   • Parietal  cells  at  the  apical  membrane  secrete  H+  into  the  gastric  lumen  via   primary  active  transport  (ATPase)   o H+/K+  ATPase  pumps  transport  H+  uphill  against  a  million-­‐to-­‐one   concentration  gradient  into  the  lumen  of  the  stomach     o Transport  K+  in  the  opposite  direction   o Potassium  recycling:  the  K  inside  the  parietal  cell  leaks  out  through  K   channels  to  prevent  depletion  of  Kin  the  gastric  lumen   o Parietal  cells  at  the  apical  surface  have  many  microvilli  with  a  high   surface  area  to  allow  the  insertion  of  a  large  number  of  H/K  pumps   • Parietal  cells  at  the  basolateral  membrane  take  in  Cl-­‐  against  its   electrochemical  gradient  by  coupling  its  transport  to  the  downhill  movement   of  bicarbonate   o Bicarbonate  is  produced  within  the  parietal  cells  by  the  dissociation  of   carbonic  acid   o Carbonic  acid  =  CO2  +  H2O  via  carbonic  anhydrase   o Therefore,  Cl-­‐  is  secreted  by  facultative  diffusion,  as  well  as  H+  into   the  gastric  juice  while  bicarbonate  is  secreted  into  the  blood   o The  secretion  of  Cl-­‐  and  K+  recycling  is  necessary  for  continues   activity  of  the  H/K  pumps   • Secretion  of  HCl  by  the  parietal  cells  is  stimulated  by  gastrin,  histamine,  and   ACh   o Gastrin  enters  general  circulation  and  can  stimulate  the  parietal  cells   directly  by  binding  to  receptors  on  the  parietal  cell  basolateral   membrane     o Gastrin  stimulation  is  mostly  indirect  –  gastrin  stimulates  ECL  cells  to   secrete  histamine  à  histamine  acts  as  a  paracrine  regulator  to   stimulate  parietal  cells  to  secrete  HCl   § Histamine  stimulation  of  parietal  cells  is  mediated  by  the  H2   type  of  histamine  receptor  –  different  from  H1  type  involved  in   allergic  reactions   • Parasympathetic  neurons  of  the  vagus  nerve  stimulate  both  parietal  and  ECL   cells  –  stimulation  of  ECL  cells  is  most  important  effect   • High  concentration  of  HCl  from  the  parietal  cells  makes  gastric  juice  very   acidic  –  pH  <2   o Strong  acidity  serves  3  functions:   § Ingested  proteins  are  denatured  at  low  pH  –  become  more   digestible     § Under  acidic  conditions,  weak  pepsinogen  enzymes  partially   digest  each  other  à  frees  the  fully  active  pepsin  enzyme  as   small  inhibitory  fragments  are  removed   § Pepsin  is  more  active  under  acidic  conditions  à  catalyzes  the   hydrolysis  of  peptide  bonds  in  the  ingested  protein   • Thus,  cooperative  activites  of  pepsin  and  HCl  permit  the  partial  digestion  of   food  protein  in  the  stomach   • Since  the  strong  acid  and  pepsin  could  damage  the  lining  of  the  stomach,   defense  mechanisms  are  necessary   o Adherent  layer  of  mucus  –  first  line  of  defense   § Stable  gel  of  mucus  that  is  stuck  to  the  gastric  epithelial  surface   § Contains  alkaline  bicarbonate  –  results  in  a  nearly  neutral  pH   at  the  epithelial  surface   § Major  barrier  to  potential  damage  to  the  stomach  caused  by   pepsin  by  slowing  its  diffusion  so  that  it  doesn’t  normally  reach   the  epithelial  cells   o Other  important  protective  mechanisms:     § Tight  junctions  between  epithelial  cells  –  prevent  acid  and   pepsin  from  leaking  past  the  barrier   § Rapid  rate  of  epithelial  cell  division  replaces  the  entire   epithelium  every  3  days  –  damaged  cells  can  be  rapidly   replaced   Digestion  and  Absorption   • Proteins  are  only  partially  digestion  in  stomach     • Carbohydrates  and  fats  are  not  digested  at  all  by  pepsin  –  almost  all  products   of  digestion  are  absorbed  through  the  wall  of  the  small  intestine   o Alcohol  and  aspirin  can  be  absorbed  across  stomach  wall  due  to  lipid   solubility  –  promotes  damage  to  gastric  mucosa   • Peptic  ulcers  –  erosions  of  the  mucosa  of  the  stomach  (produced  by  the   action  of  HCl)  that  penetrate  through  the  Muscularis  mucosa   o Zollinger-­‐Ellison  Syndrome:  ulcers  in  the  duodenum  produced  by   excess  gastric  acid  resulting  from  very  high  levels  of  gastrin  –  released   by  a  gastrin-­‐secreting  tumor   § Shows  that  excessive  gastric  acid  can  cause  ulcers  in  the   duodenum   o Stomach  ulcers  are  due  to  mechanisms  that  reduce  the  barriers  of  the   gastric  mucosa  to  self-­‐digestion   § Ulcers  are  produced  by  Helicobacter  pylori  bacteria  –  have  adaptations  that   allow  them  to  survive  in  high  acidic  environments   o Can  be  treated  with  a  drug  regimen  consisting  of  a  proton  pump   inhibitor  combined  with  2  antibiotics   § Ulcers  can  also  be  caused  by  NSAIDs  (Nonsteroid  Anti-­‐Inflammatory  Drugs)  –   aspirin  and  ibuprofen     o Damage  the  gastric  mucosa  because  NSAIDs  inhibit  prostaglandin   synthesis  –  prostaglandin  contributes  to  the  mucosa  barrier  by   stimulating  mucus  and  bicarbonate  production   § Acute  gastritis:  inflammation  that  occurs  when  gastric  barriers  are  broken   down  and  acid  can  leak  through  the  mucosa  to  the  submucosa   o Causes  direct  damage  and  stimulates  inflammation     o Histamine  released  in  response  will  stimulate  further  acid  secretion  –   causing  further  damage  à  why  drugs  that  block  H2  histamine   receptors  may  be  used  to  treat  gastritis     § Duodenum  is  normally  protected  from  gastric  acid  by  a  number  of  defenses   o Adherent  layer  of  mucus  –  surrounding  epithelium  normally  exposed   to  a  neutral  pH   o Bicarbonate  secretion  by  the  Brunner’s  glands  in  the  submucosa  –   glands  unique  to  the  duodenum     o Acidic  chyme  is  neutralized  by  the  buffering  action  of  bicarbonate  in   alkaline  pancreatic  juice  –  released  into  duodenum  upon  arrival  of   acidic  chyme   Small  Intestine   • The  portion  of  the  GI  tract  between  the  pyloric  sphincter  of  the  stomach  and   the  ileocecal  valve  opening  into  the  large  intestine   • Small  diameter  but  longest  part  of  the  GI  tract   • Main  site  of  digestion  and  absorption  of  liberated  nutrients   • Portions:   o Duodenum  –  initial  section  extending  from  the  pyloric  sphincter   o Jejunum  –  next  2/5  of  the  small  intestine   o Ileum  –  last  3/5  of  the  small  intestine  –  empties  through  the  ileocecal   valve   • Products  of  digestion  are  absorbed  across  the  epithelial  lining  of  the   interstitial  mucosa  at  a  rapid  rate  due  to  extensive  foldings  of  mucosa   o Absorption  of  carbohydrates,  lipids,  amino  acids,  calcium  and  iron   occurs  primarily  in  the  duodenum  and  jejunum     o Absorption  of  bile  salts,  vitamin  B12,  water,  and  electrolytes  occurs   primarily  in  the  ileum     • Plicae  circulares  –  large  folds  formed  by  the  mucosa  and  submucosa   o Cause  content  to  spiral  through  to  ensure  that  there  is  a  mixing  with   secretions  from  the  lumen  of  the  small  intestine   o Allows  us  to  bring  enzymes  into  contact  with  material  we  are   digesting   o Villi  –  microscopic  folds  of  mucosa  further  increasing  surface  area   o Microvilli  –  foldings  on  the  plasma  membrane  of  the  cells  that  line   these  villi   § Used  interchangeable  with  brush  border     • Villus:  fingerlike  fold  of  mucosa  that  projects  into  intestinal  lumen   o Covered  with  columnar  epithelial  cells  –  including  mucus-­‐secreting   goblet  cells   o Lamina  propria:  forms  the  connective  tissue  core  of  each  villus   § Contains  lymphocytes,  blood  capillaries  and  central  lacteal   (lymphatic  vessel)  –  absorbed  monosaccharides  and  amino   acids  enter  the  blood  capillaries  and  fat  enters  the  lacteal   o Intestinal  crypts:  narrow  pouches  that  open  through  pores  into  the   intestinal  lumen  –  formed  from  invaginations  of  the  epithelium  at  the   base  of  the  villi   § Paneth  cells  –  secrete  antibacterial  lysozyme  and  bactericidal   peptides  (defensins)   • Found  at  the  bottom  of  the  intestinal  crypts  –  only  in   small  intestine,  not  large   • Secretions  help  maintain  intestinal  stem  cells   § Intestinal  stem  cells  –  found  with  Paneth  cells     • Divide  mitotically  to  replenish  and  produce  specialized   cells  of  the  intestinal  mucosa   o Intestinal  epithelium  is  renewed  every  5-­‐7  days   § Mitosis  at  the  base  of  the  villi  in  the  crypts  occurs  once  a  day   § Mitosis  at  the  top  of  the  crypts  stop  and  cells  differentiate  into   secretory  cells  (Paneth  cells,  goblet  cells  and  endocrine  cells)   and  enterocytes  (intestinal  epithelial  cells)   § The  new  cells  migrate  to  the  top  of  the  villi  and  those   previously  at  the  top  undergo  apoptosis     Intestinal  Enzymes   • Brush  border  enzymes  –  digestive  enzymes  in  the  plasma  membrane  of  the   microvilli  that  hydrolyze  disaccharides,  polypeptides  and  other  substrates     o Remain  attached  to  plasma  membrane  –  not  secreted  into  lumen   o Enterokinase:  required  for  activation  of  the  protein-­‐digesting  enzyme   trypsin   Intestinal  Contractions  and  Motility     • 2  types  of  contractile  movement   o Peristalsis     § Weak  in  small  intestine   § Important  in  esophagus  and  stomach   § Stretch  and  chemical  changes  in  a  bolus  are  relayed  to  the   enteric  nervous  system  –  directs  excitation  and  smooth  muscle   contraction  behind  bolus  and  inhibition  and  relaxation  ahead   of  it   § Intestinal  motility  is  slow  for  proper  absorption     o Segmentation  –  serves  to  mix  chyme  with  luminal  fluids;  major   contractile  event  in  the  small  intestine     § Localized  event  of  contractions  and  relaxations   § One  section  with  be  contracted  and  segment  after  it  is  relaxed   • Contractions  of  the  intestinal  smooth  muscle:   o Occur  automatically  in  response  to  endogenous  pacemaker  activity   o Slow  waves  –  rhythm  of  contraction  paced  by  graded  depolarizations   § Interstitial  cells  of  Cajal:  unique  pacemaker  cells  that  produce   slow  waves  –  neither  neurons  nor  smooth  muscle  cells   • Long  projections  that  join  them  to  each  other  and   smooth  muscle  cells  through  gap  junctions   • Gap  junctions  conduct  depolarization  along  cells  –   allows  entire  muscularis  to  work  as  a  functional   syncytium     • Serve  to  depolarize  adjacent  smooth  muscle  cells   § Can  only  spread  a  short  distance  and  must  be  regenerated  by   next  region  of  cells  –  produces  segmentation     • Autonomic  nerves  modify  the  automatic  contractions  by  influencing  the   enteric  nervous  system   Large  Intestine   • Absorbs  water,  electrolytes  and  vitamins  –  little  to  no  digestive  function   • Extends  from  the  ileocecal  valve  to  the  anus   • Chyme  from  ileum  of  small  intestine  is  passed  to  large  intestine  into  the   cecum   • Waste  passes  from  ascending  colon  à  transverse  colon  à  descending  colon   à  sigmoid  colon  à  rectum  à  anal  canal     • Intestinal  microbiota:  microorganisms  of  the  large  intestine     o Necessary  because  they  provide  Vitamin  B,  Vitamin  K  and  folic  acid   o Produce  short-­‐fatty  acid  chains  by  bacterial  fermentation  that   stimulate  active  Na  and  Cl  absorption  –  results  in  secretion  of  water   Accessory  digestive  organs   o Liver,  gallbladder  and  pancreas   o Important  digestive  organs  –  provide  majority  of  digestive  enzymes  for  small   intestine  as  well  as  buffering  substances  to  adjust  acidic  chyme  coming  from   stomach   Pancreas     • Soft,  glandular  organ  that  has  both  exocrine  and  endocrine  functions   o Endocrine  function:  performed  by  pancreatic  islets  that  secrete   insulin  and  glucagon  into  the  blood   o Exocrine  function:  secretes  pancreatic  juice  into  duodenum   § Acini  –  exocrine  secretory  units   • Pancreatic  juice:  product  of  Acinar  cells  and  epithelial  cells   o Contains  bicarbonate  (produced  by  epithelial  cells)  and  digestive   enzymes  (produced  by  Acinar  cells)   § Amylase  –  digests  starch   § Trypsin  –  digests  protein   § Lipase  –  digests  triglycerides   § Note:  complete  digestion  by  the  small  intestine  requires  both   enzymes  from  the  pancreatic  juice  and  brush  border   o The  enzymes  are  produced  in  an  inactive  form  (zynogens)  –  must  be   activated  once  they  get  to  the  small  intestine   § Activated  by  trypsin  which  is  converted  from  trypsinogen  by   enterokinase     § Must  be  inactive  in  pancreas  so  they  don’t  break  down  the   walls  of  the  pancreas   o Acini  absorb  Cl  and  secrete  bicarbonate  so  pancreatic  juice  has  much   more  bicarbonate  than  Cl-­‐   § CFTR  (cystic  fibrosis  trans-­‐membrane  conductance  regulator)   transports  Cl-­‐  back  into  lumen   § Dissociation  of  carbonic  acid  produces  this  bicarbonate  and   H+,  which  is  secreted  into  the  blood   Liver   • Hepatocytes:  liver  cells  the  form  hepatic  that  are  separated  from  each  other   by  sinusoids  –  discontinuous  capillaries  with  fenestrations   o Hepatic  sinusoids  are  much  more  permeable  than  other  capillaries   due  to  their  lack  of  a  diaphragm  or  basement  membrane   § Kupffer  cells:  phagocytic  cells  in  the  sinusoids   o Fenestrations,  lack  of  basement  membrane  and  plate  structure  allow   intimate  contact  between  hepatocytes  and  blood   • Hepatic  Portal  System:  unique  pattern  of  blood  circulation   o Capillaries  in  digestive  tract  drain  into  the  hepatic  portal  veinà   capillaries  in  the  liver  à  hepatic  vein   o Hepatic  portal  vein:  brings  in  deoxygenated  blood  that  is  nutrient  rich   into  the  liver   o Hepatic  vein:  returns  blood  to  general  circulation  to  the  inferior  vena   cava   o Hepatic  artery:  brings  oxygenated  blood  to  liver     § Accounts  for  the  rest  of  the  blood  to  the  liver  (75%  delivered   via  hepatic  portal  vein)   § Adjusted  to  compensate  for  changes  in  blood  flow  through  the   hepatic  portal  vein  à  allows  a  relatively  constant  blood  flow   needed  to  maintain  hepatic  clearance   • Liver  lobules:  functional  units  of  the  hepatic  plates   o Branches  of  the  hepatic  portal  vein  and  hepatic  are  in  the  periphery   surrounding  a  middle  central  veins   o Arterial  and  venous  blood  mix  and  migrate  from  periphery  to  central   vein   § Central  veins  of  different  lobules  converge  to  form  the  hepatic   vein   o Bile  canaliculi:  channels  within  each  hepatic  plate  –  bile  produced  by   hepatocytes  is  secreted  into  the  canaliculi   § Drained  at  the  periphery  of  lobules  by  bile  ducts  à  then   drained  into  hepatic  ducts  that  carry  bile  away  from  the  liver   § Blood  and  bile  do  not  mix  in  the  liver  because  blood  travels  in   the  sinusoid  in  the  opposite  direction   o Portal  triad:  branch  of  bile  duct,  hepatic  portal  vein  and  hepatic  artery   • Functions  of  the  liver:     o Blood  detoxification  via   § Phagocytosis  by  Kupffer  cells   § Chemical  alteration  of  biologically  active  molecules  (hormones   and  drugs)   § Production  of  urea,  uric  acid  and  other  molecules  that  are  less   toxic  than  parent  compounds   § Excretion  of  molecules  in  bile   o Carbohydrate  metabolism  via   § Conversion  of  blood  glucose  to  glycogen  and  fat   § Production  of  glucose  from  liver  glycogen  and  from  other   molecules  by  glycogenesis     § Secretion  of  glucose  into  the  blood   o Lipid  metabolism  via   § Synthesis  of  triglycerides  and  cholesterol   § Excretion  of  cholesterol  in  bile     § Production  of  ketone  bodies  from  fatty  acids   o Protein  synthesis  via   § Production  of  albumin   § Production  of  plasma  transport  proteins   § Production  of  clotting  factors  (fibrinogen,  prothrombin,  etc.)   o Secretion  of  bile  via   § Synthesis  of  bile  salts   § Conjugation  and  excretion  of  bile  pigment  (bilirubin)     Enterohepatic  Circulation   • Some  compounds  absorbed  by  small  intestine  and  enter  hepatic  circulation   are  re-­‐circulated  between  liver  and  small  intestine   o Can  be  retaken  up,  put  back  in  liver  and  go  through  bile  then  repeat   • Variety  of  exogenous  compounds  excreted  by  liver  in  bile  –  thus  liver  can   “clear”  blood  of  particular  compounds,  which  are  eliminated  in  feces   • Drugs  are  processed  in  liver  –  detoxified,  broken  down  and  eliminated  from   the  body   • Bile  salts  are  recycled   o Bilirubin  –  broken  down  part  of  heme   § Broken  down  by  bacteria   § Gives  coloration  to  feces   § Can  be  converted  into  urobilinogen  –  can  be  recycled  too  but   can  be  picked  up  by  the  kidneys  and  then  is  responsible  for   coloration  in  urine   Lipid  Transport  and  Utilization   • Lipoproteins:  lipid-­‐protein  complexes  that  solubilize  the  hydrophobic  lipids   as  well  as  providing  signals  that  regulate  lipid  entry/exit  at  target  cells   • Emulsification:  process  in  which  bile  salt  miscelles  are  secreted  into  the   duodenum  and  act  as  detergents  to  break  up  the  fat  droplets  into  tiny   emulsification  droplets  of  triglycerides     o Is  not  chemical  digestion  –  bonds  are  not  hydrolyzed   o Aids  digestion  because  the  small  droplets  present  a  greater  surface   area   • Pancreatic  lipase:  fat-­‐digesting  enzyme  aided  by  colipase   o Colipase:  protein  secreted  by  liver  that  coats  the  droplets  and  anchors   the  lipase  enzyme  to  them   o Lipase  hydrolyzes  two  of  the  three  fatty  acids  into  free  fatty  acids  and   monoglycerides   • Phospholipase  A:  digests  phospholipids  further  after  the  removal  of  the  first   two  fatty  acids  into  fatty  acids  and  lysolecithin     • The  free  fatty  acids,  monoglycerides  and  lysolecithin  are  more  polar  in  this   form  –  quickly  enter  micelles  of  bile  salts  à  move  to  the  brush  border  for   absorption     o They  can  leave  the  micelles  and  enter  the  intestinal  epithelial  cells  –   used  to  resynthesize  triglycerides  and  phospholipids   o Triglycerides,  phospholipids  and  cholesterol  are  combined  with   protein  inside  the  epithelial  cells  to  form  small  particles  –   chylomicrons,  which  are  secreted  by  exocytosis  into  the  central  lacteal   • ApoE:  protein  constituent  the  chylomicrons  acquire  once  in  the  blood  –   allows  chylomicrons  to  bind  to  receptor  to  be  hydrolyzed  to  release  free  fatty   acids   • VLDL  (very  low  density  lipoproteins):  cholesterols  and  triglycerides   combined  with  other  apolipoproteins  secreted  into  the  blood  to  deliver   triglycerides  to  other  organs   • LDL  (low  density  lipoproteins):  new  particle  formed  when  triglycerides  are   removed  from  VDLD  –  transports  cholesterol     • HDLP  (high  density  lipoproteins);  returns  excess  cholesterol  to  the  liver     Neural  and  Endocrine  Regulation  of  the  Digestive  System   • Modify  the  activity  of  the  GI  tract   • GI  tract  serves  as  both  an  endocrine  gland  and  target  for  various  hormones   • Gastric  function:  divided  into  3  phases   o Cephalic  phase:  control  by  the  brain  via  the  vagus  nerve   § Stimulated  by  sight  smell  and  thought  of  food     § Stimulates  chief  cells  to  secrete  pepsinogen  and  parietal  cells   to  secrete  HCl   § Major  mechanism  is  indirect  –  vagus  nerve  stimulates  G-­‐cells   to  secrete  gastrin  à  stimulates  ECL  cells  to  secrete  histamine   àstimulates  paracrine  cells  to  secrete  HCl   o Gastric  Phase:  stimulated  by  arrival  of  food  in  the  stomach   § Stimulated  in  response  to  distention  of  the  stomach  (by   amount  of  chyme)  and  chemical  nature  of  the  chyme  –  act   primarily  via  the  secretion  of  gastrin   § Partially  digested  proteins  stimulate  gastrin  secretion   § Gastrin  stimulates  pepsinogen  secretion  from  chief  cells  and   HCl  from  parietal  cells  (indirectly)   § Positive  feedback  loop  develops:  as  more  HCl  and  pepsinogen   are  secreted,  more  partially  digested  proteins  are  released  à   stimulates  additional  secretion  of  gastrin  à  additional   secretion  of  HCl  and  pepsinogen   § Negative  feedback  loop:  as  the  pH  drops,  D  cells  secrete   somatostatin  à  inhibits  gastrin  secretion  from  G  cells  à   inhibits  HCl  secretion  from  parietal  cells     o Intestinal  Phase:  inhibition  of  gastric  activity  as  chyme  enters  small   intestine   § As  duodenal  distention  and  osmolality  increase,  gastric   motility  and  secretion  are  inhibited   § Enterogastrone:  gastric  inhibitory  hormone  stimulated  by  the   presence  of  fat  in  the  chyme   § Hormones   • Secretin:  buffers  acidic  of  chyme  coming  from  the   stomach  into  the  small  intestine   • CCK  –  cholecystokinin:  produced  in  presence  of  fat  and   protein   • GIP  –  glucose-­‐dependent  insulinotropic  peptide:   stimulates  beta  cells  in  pancreas  to  release  insulin  in   response  to  glucose  in  food     • Pancreatic  juice  and  bile  regulation:   o Arrival  of  chyme  into  small  intestine  also  stimulates  secretion  of   pancreatic  juice  and  bile   § Secretin:  stimulates  live  to  secrete  bile  after  a  meal   § CCK:  increases  the  blow  of  bile  into  the  duodenum      


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