2 : Glandular Epithelium Laboratory -­‐ Year 1, Fall Term Dr. Heather Yule ([email protected]) October 21, 2014

Slides for study: 75 (Salivary ), 355 ( Tail), 8 4 (Atrophic ), 49 (Active Mammary Gland) and 50 (Resting Mammary Gland)

Electron micrographs for : study EM: Serous in parotid gland EM: Mucous acinus in mixed EM: Pancreatic acinar cell

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

Specific Objectives:

1. Describe key histological differences between endocrine and exocrine including their development.

2. Compare three modes of secretion in glands; , and .

3. Explain the functional significance of polarization of glandular epithelial cells.

4. Define the terms parenchyma, stroma, mucous acinus, serous acinus and serous a demilune and be able to them identify in glandular tissue.

5. Distinguish exocrine and endocrine pancreas.

6. Compare the histology of resting, lactating and postmenopausal mammary glands.

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

“This copy is made solely for your personal use for research, private study, education, parody, satire, criticism, or review only. Further reproduction, fixation, distribution, transmission, dissemination, communication, or any other uses, may be an infringement of copyright if done without securing the permission of the copyright owner. You may not distribute, e-mail, or otherwise communicate these materials to any other person.” (Full statement from http://copyright.ubc.ca/faq/digital-classroom/) 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 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. ), 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?

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

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 E M: “ 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.

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 for used 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) Color Textbook of Histology, Gartner -­‐ & Hiatt, Fig.5 24. Used in second year. with permission. Copyright © 2006 Elsevier Inc. All rights reserved.

Exocrine Gland Classification -­‐ Mucous, Serous or Mixed/Seromucous Glands • Mucous cells produce ucus m ( 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 mucous both 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?

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 in to 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 nctions pancreas fu 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 production milk 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 lveoli a 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.

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

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 stroma. and entering the

“Invasive ductal 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.