Epithelium  2:  Glandular  Epithelium  Histology  Laboratory  -­‐  Year  1,  Fall  Term  Dr.  Heather  Yule  (heather.yule@ubc.ca)    

October  21,  2014      Slides  for  study:    75  (Salivary  Gland),  355  (Pancreas  Tail),  48  (Atrophic  Mammary  Gland),  49  (Active  Mammary  Gland)  and  50  (Resting  Mammary  Gland)    Electron  micrographs  for  study:    EM:  Serous  acinus  in  parotid  gland  EM:  Mucous  acinus  in  mixed  salivary  gland  EM:  Pancreatic  acinar  cell            Specific  Objectives:    1. Describe  key  histological  differences  between  endocrine  and  exocrine  glands  including  

their  development.      2. Compare  three  modes  of  secretion  in  glands;  holocrine,  apocrine  and  merocrine.    3. Explain  the  functional  significance  of  polarization  of  glandular  epithelial  cells.    4. Define  the  terms  parenchyma,  stroma,  mucous  acinus,  serous  acinus  and  a  serous  

demilune  and  be  able  to  identify  them  in  glandular  tissue.    5. Distinguish  exocrine  and  endocrine  pancreas.    6. Compare  the  histology  of  resting,  lactating  and  postmenopausal  mammary  glands.  

 Keywords:  endocrine  gland,  exocrine  gland,  holocrine,  apocrine,  merocrine,  polarity,  parenchyma,  stroma,  acinus,  myoepithelial  cell,  mucous  gland,  serous  gland,  mixed  or  seromucous  gland,  serous  demilune,  exocrine  pancreas,  endocrine  pancreas  (pancreatic  islets),  resting  mammary  gland,  lactating  mammary  gland,  postmenopausal  mammary  gland      

Main  Objective:  Understand  key  histological  features  of  glandular  epithelium  and  relate  structure  to  function.  

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Development  of  Glands:    Endocrine  and  exocrine  glands  develop  from  surface  epithelium  where  cells  proliferate,  penetrate  underlying  connective  tissue  and  differentiate  into  secretory  cells.  Endocrine  glands  lose  their  connection  to  the  surface  (“ductless”)  and  release  their  product  into  the  bloodstream.  Exocrine  glands  retain  their  connection  to  the  surface  and  release  their  product  into  a  duct  or  lumen.        For  more  information  on  glandular  development  please  see  a  histology  text  (i.e.  Netter’s  Essential  Histology  1st  Edition  p.42  or  Gartner  and  Hiatt  3rd  Edition  p.103).    Modes  of  Secretion:  In  holocrine  glands  (i.e.  sebaceous  gland),  secretory  cells  disintegrate  and  release  their  product.  New  cells  are  continuously  replacing  lost  secretory  cells.  In  apocrine  glands  (i.e.  mammary  gland  –  lipid  secretion),  a  small  portion  of  the  apical  cytoplasm  is  released  along  with  the  secretion.  In  merocrine  glands  (i.e.  salivary  gland,  pancreas,  mammary  gland  –  protein  secretion),  their  product  is  released  by  exocytosis.    

 Can  you  label  the  modes  of  secretion  shown  here?    Which  mechanism  is  the  most  common?    

 Epithelial  Cell  Polarization:  Secretory  cells  exhibit  polarity  meaning  they  have  distinct  cellular  domains.  Examine  an  EM  of  a  serous  (protein  secreting)  cell  and  identify  organelles  found  in  the  basal  and  apical  domains  of  the  cell.    

 Try  the  EM:  “Serous  acinus  in  parotid  gland”.  What  organelles  can  you  identify  in  the:  basal  domain?  _______________________________________________  apical  domain?  ______________________________________________  

Why  are  these  cells  polarized?  How  does  polarization  relate  to  function?      Are  mucous  cells  also  polarized?    Hint:  Examine  the  EM:  “Mucous  acinus  in  mixed  salivary  gland”.    

   

Netter’s Essential Histology, Ovalle & Nahirney, Fig.2.15, 2.16. Used with permission. Copyright © 2008 Elsevier Inc. All rights reserved.

Color  Textbook  of  Histology,  Gartner  &  Hiatt,  Fig.5-­‐19.  Used  with  permission.  Copyright  ©  2006  Elsevier  Inc.  All  rights  reserved.  

Slide  75  –  Mixed  Salivary  Gland  (H&E):  (UBC,  CPS  Virtual  Slidebox,  Slide  #75)  This  slide  illustrates  many  key  histological  features  of  exocrine  glands.    Parenchyma  versus  Stroma  Glandular  parenchyma  (epithelial  component)  is  the  functional  portion  of  a  gland  in  that  epithelial  cells  produce  a  glandular  product.  Conversely,  glandular  stroma  (connective  tissue  component)  is  the  supportive  portion  of  a  gland  and  often  divides  the  gland  into  compartments  called  lobules.      Can  you  identify  parenchyma  and  stroma  in  slide  75?  Are  these  terms  used  for  endocrine  glands  too?    Structure  of  Exocrine  Glands  Secretions  are  produced  by  epithelial  cells  (cuboidal,  columnar  or  pyramidal  shaped)  located  in  the  dilated  ends  of  the  gland.  They  often  form  rounded  clusters  called  acini  (singular  acinus)  that  are  surrounded  by  contractile  myoepithelial  cells  and  an  outer  basement  membrane.  Myoepithelial  cells  are  difficult  to  identify  in  slide  75  so  please  do  NOT  spend  time  trying  to  find  them,  just  be  aware  of  their  presence.  From  acini,  secretions  drain  into  an  excretory  duct  system;  small  ducts  within  lobules  merge  into  larger  ducts  seen  between  lobules.  You  will  learn  more  about  the  duct  system  (intercalated,  intralobular  and  interlobular  ducts)  in  second  year.      

Exocrine  Gland  Classification  -­‐  Mucous,  Serous  or  Mixed/Seromucous  Glands  • Mucous  cells  produce  mucus  (mucin  proteins  +  water  =  a  viscous,  lubricating  substance)  

which  is  lost  in  preparation,  thus  mucous  cells  appear  washed  out.    Glands  composed  entirely  of  mucous  acini  are  classified  as  mucous  glands.    

• Serous  cells  produce  a  protein-­‐rich  product  (often  an  enzyme)  which  takes  up  stain  well,  thus  serous  cells  appear  eosinophilic.  Glands  composed  entirely  of  serous  acini  are  classified  as  serous  glands.    

• Many  glands  contain  both  mucous  acini  and  serous  acini  and  are  called  mixed  or  seromucous  glands.  Additionally,  in  mixed  glands,  some  mucous  acini  are  capped  with  serous  cells  called  a  serous  demilune.    

In  slide  75,  a  mixed  salivary  gland,  can  you  identify  mucous  acini,  serous  acini  and  a  serous  demilune?  What  is  the  main  protein  product  secreted  from  serous  cells  in  slide  75?      

Color  Textbook  of  Histology,  Gartner  &  Hiatt,  Fig.5-­‐24.  Used  with  permission.  Copyright  ©  2006  Elsevier  Inc.  All  rights  

reserved.  

Slide  355  –  Pancreas  Tail  (H&E):  (UBC,  CPS  Virtual  Slidebox,  Slide  #355)  The  pancreas,  an  accessory  digestive  organ,  is  a  good  example  of  a  gland  with  both  exocrine  and  endocrine  functions.    99%  of  the  pancreas  is  an  exocrine  gland  secreting  digestive  enzymes  into  the  duodenum.  The  structure  of  the  exocrine  pancreas  is  similar  to  the  salivary  gland  with  rounded  secretory  acini  emptying  into  a  duct  system.    In  slide  355,  can  you  identify  pyramidal  shaped  pancreatic  acinar  cells?    In  the  EM  “Pancreatic  Acinar  Cell”  (EM  on  Medicol  and  found  in  ‘Netter’s  Essential  Histology,  Ovalle  and  Nahirney,  Fig  .2.5’  Used  with  permission.  Copyright  ©  2008  Elsevier  Inc.  All  rights  reserved.),  can  you  see  the  polarization  and  apical  secretory  vesicles  within  the  pancreatic  acinar  cells?      

An  unusual  feature  observed  in  some  sections  of  pancreatic  acini  are  centroacinar  cells  bulging  into  the  acinar  lumen.  These  pale  staining  cells  are  the  first  part  of  the  duct  system  and  they  secrete  a  bicarbonate-­‐rich  fluid.    Can  you  find  a  pancreatic  centroacinar  cell  in  slide  355?  Why  is  bicarbonate-­‐rich  fluid  required  from  these  cells?  

 The  remaining  1%  of  the  pancreas  functions  as  an  endocrine  gland.  Islands  of  pale  staining  cells  within  the  exocrine  pancreas  are  called  pancreatic  islets  or  islets  of  Langerhans.  Pancreatic  islets  produce  different  types  of  hormones  involved  in  regulating  blood  glucose.  You  will  learn  more  about  the  histology  of  the  pancreas  in  second  year.    Can  you  distinguish  the  exocrine  pancreas  from  the  endocrine  pancreas?      Slides  48  (Atrophic),  49  (Active)  and  50  (Resting)  –  Mammary  Gland  (all  H&E):    (UBC,  CPS  Virtual  Slidebox,  Slides  #48,  49  and  50)  The  mammary  gland  undergoes  substantial  change  throughout  life  and  is  a  good  example  of  what  glandular  epithelium  is  capable  of.    In  females,  the  mammary  gland  develops  at  puberty  under  the  influence  of  ovarian  hormones  yet  it  remains  inactive  until  pregnancy.  During  pregnancy,  changes  in  hormones  stimulate  further  development  of  the  mammary  gland  and  eventually  milk  production  from  mammary  epithelial  cells  following  birth.  With  infant  suckling,  myoepithelial  cells  contract,  causing  mammary  epithelial  cells  to  expel  milk.    Mammary  Gland  Structure  The  mammary  gland  is  a  compound  tubuloalveolar  (or  tubuloacinar)  gland.  Each  gland  is  made  up  of  15-­‐20  lobes  drained  by  a  duct  system  ending  with  a  lactiferous  duct  and  sinus  which  drain  into  the  nipple.    For  an  illustration  of  mammary  gland  structure,  please  see  a  histology  text  (i.e.  Netter’s  Essential  Histology  1st  Edition  p.46,  Gartner  and  Hiatt  3rd  Edition  p.486,  Ross  and  Pawlina  6th  Edition  p.864).      

Glandular  parenchyma  is  divided  into  secretory  and  ductal  portions.  Cuboidal  secretory  cells  surrounded  by  myoepithelial  cells  and  a  basement  membrane  comprise  the  alveoli  in  active  or  lactating  mammary  glands.  Note:  Secretory  alveoli  are  only  present  in  lactating  mammary  glands!  The  smallest  ducts  are  lined  by  simple  cuboidal  epithelium  which  becomes  stratified  cuboidal  in  larger  ducts  and  stratified  squamous  near  the  nipple.      Glandular  stroma  supports  and  divides  the  mammary  gland  into  lobes  and  smaller  lobules.  Within  lobules,  loose  connective  tissue  is  abundant  whereas  surrounding  the  lobules  dense  irregular  connective  tissue  and  adipose  are  more  common.  The  amount  and  type  of  stroma  depends  upon  physiological  stage  and  age.    

Slide  50  is  from  a  resting,  inactive  or  non-­‐lactating  mammary  gland.  Can  you  identify:  

Ø parenchyma  –  small  terminal  ducts  within  lobules,  large  ducts  between  lobules  

Ø stroma  –  loose  connective  tissue  within  lobules,  dense  irregular  connective  tissue  surrounding  lobules  

 Slide  49  is  from  an  active  or  lactating  mammary  gland.  Individual  lobules  are  difficult  to  identify  as  secretory  alveoli  now  fill  the  gland  and  crowd  out  the  connective  tissue.  Additionally,  many  alveolar  lumina  and  ducts  are  filled  with  milk.  What  are  the  main  components  of  milk?  

 Slide  48  is  from  an  atrophic  or  postmenopausal  mammary  gland.  After  menopause  and  the  withdrawal  of  ovarian  hormones,  mammary  glands  slowly  involute.  Alveolar  epithelial  cells  undergo  apoptosis,  many  ducts  regress  and  connective  tissue  atrophies.  

         Clinical  Point:  Breast  cancer  is  the  most  common  malignancy  in  women  and  usually  occurs  after  menopause.  Most  cancers  arise  from  ductal  epithelium  (such  as  lactiferous  ducts)  and  “invasive”  cancers  show  evidence  of  breaking  through  the  basement  membrane  and  entering  the  stroma.      “Invasive  ductal  carcinoma  of  the  breast”      

Sastre-­‐Garau  X  et  al.,  Increased  cell  size  and  Akt  activation  in  HER2-­‐2/neu-­‐overexpressing    invasive  ductal  carcinoma    of  the  breast,    Histopathology,  45,  142-­‐147,  2004.      Used  with  permission.  Copyright  ©  2004  John  Wiley  and  Sons.  All  rights  reserved.  

What  are  the  main  histological  differences  between  resting,  active  and  postmenopausal  mammary  glands?