Microstructure+Epi+Dent+Keefe+Student+2024.pdf

Microstructure of Epithelium DR. KAT HLEE N K EE FE D102: A NATOMICA L S CIE NCE S KATHY MKE EFE @T E MPLE. EDU Disclosure I currently have no relationships of any kind with any company whose products or services in any way relate to the practice of medicine, medical education, or research L...

Microstructure of Epithelium DR. KAT HLEE N K EE FE D102: A NATOMICA L S CIE NCE S KATHY MKE EFE @T E MPLE. EDU Disclosure I currently have no relationships of any kind with any company whose products or services in any way relate to the practice of medicine, medical education, or research Learning Objectives List the histologic characteristics of epithelia and their functions Explain the relevance of epithelial cell polarity and the structure and function of surface specializations Recall the major classes of cell adhesion molecules, their contribution to intercellular junctions and how they control the passage of materials across an epithelium Describe composition of the basement membrane, mechanism of attachment to the base of overlying cells and how mutations in molecules in the basement membrane or breach of the basement membrane may contribute to disease Epithelium is a Basic Tissue Tissue – a group of cells that work together to perform a specific function All the organs of your body are composed of 4 basic tissues – epithelium, muscle, nerve and connective tissue Epithelia are sheets of cells that: Cover or line internal and external body surfaces Form secretory glands and ducts Functions: Protection (e.g. epidermis) All substances entering or leaving an organ must cross this tissue Absorption (e.g. intestinal lining) Secretion (e.g. salivary gland) General Characteristics of Epithelia Characteristics of epithelia include: Cells tightly packed together One free surface not in contact with other cells Faces the internal cavity (lumen) of the organ Attached to underlying connective tissue (CT) by an acellular basement membrane (BM) [lumen] BM is a meshwork of carbohydrates and proteins CT underneath an epithelium is called the lamina propria Lack of blood vessels (avascular) Epithelial cells derive nutrition and O2 from vessels in the Epithelium lamina propria BM Lamina propria Types of Epithelium Epithelial cells come in a variety of shapes and sizes related to their function Epithelium are classified by the following: Shape: Squamous – flattened cells wider than they are tall Cuboidal – cells relatively equal in height and width Columnar – taller than they are wide Arrangement of cells into either: Simple – a single layer of cells Stratified – multiple layers of cells Specialized – pseudostratified and transitional epithelium Simple Squamous Epithelium A single layer of flattened cells Tends to have scanty cytoplasm and flatter nuclei Cells specialized for easy diffusion across their cytoplasm E.g. appear in the air sacs of the lung, lining of blood vessels (endothelium), and structures in the kidney (longitudinal section) Simple squamous epithelium lining a small vein (cross section – H&E stain) Simple Cuboidal Epithelium Cells have about equal physical dimensions and appear square in a histological section Nuclei appear round Function in protection, absorption, synthesis and secretion of substances needed for the function of organs they line E.g. cuboidal cells lining collecting tubules of the kidneys participate in reabsorption of water Simple Columnar Epithelium Taller than they are wide Rounded nuclei Cells that function in protection, transport of materials, absorption and secretion E.g. columnar cells lining the stomach secrete mucus that serves as a protective barrier for nearby cells Found in bronchial tubes of the lungs, uterine tubes and lining the stomach and intestinal tract [lumen] Stratified Epithelium Epithelia composed of more than Apex one layer of cells Only the bottom layer touches the basement membrane Stratified Basement Columnar Membrane Nuclei in each layer are basically aligned Epithelium with each other Lamina Classified based on the shape of the propria top layer of cells: Stratified squamous Stratified cuboidal Stratified columnar Stratified Cuboidal and Columnar Epithelium Rarer type of stratified epithelium found in larger glands and the male urethra E.g. stratified cuboidal epithelia line ducts of sweat glands. Cells recycle sodium and chloride ions in sweat E.g. stratified columnar epithelia in the male urethra protect tissue from urine by secreting mucus Top layer of cells is columnar Stratified Squamous Piles of flattened cells with many layers Most common type of stratified epithelium Epithelium Not as easy to see “lines” of nuclei You can clearly see that only bottom layer connects to basement membrane Found in the vocal folds, esophagus, epidermis of the skin, vagina LP BM Stratified Squamous is Adapted for Toughness Can be seen in areas that undergo friction, and can adapt in the following ways: Can undergo keratinization: Cells synthesize keratin filaments that enhance cell toughness Cells in upper layers may eject cellular organelles (including nuclei) – in a histological section, cells closest to the lumen lack nuclei Certain cells are very mitotically active, thus this epithelium has a high turnover rate Specialized Epithelium Certain epithelia don’t fit into either simple or stratified categories Pseudostratified epithelium Has cells of different shapes and sizes – may C C C appear as if cells are in layers, however, all Epithelium cells touch the basement membrane E.g. respiratory system epithelium contains: G G Columnar cells Basal cells Goblet cells B BM C = columnar cell; G = goblet cell; B = basal stem cell; BM = basement membrane Specialized Epithelium Transitional epithelium (urothelium) is found in the bladder and ureter, and functions to: Maintain a urinary barrier to keep urine stored, even when the organ is distended A pseudostratified epithelium with two distinct appearances: Compact version when the bladder is full Taller version when the bladder is empty Each version has unique rounded cells called umbrella cells whose dense plaques help maintain barrier function These cells can have multiple nuclei  Self Study Epithelium Classification Summary Slide Cell Polarity Epithelial cells are polar – they have an asymmetric distribution of proteins and organelles within their cytoplasm Polarity is described in 3 domains: Apical (apex) – cell surface that faces the lumen Basal (base) – opposite the apical domain. In a simple epithelium, the cell surface attached to the basement membrane Lateral – cell surface attached to other cells in the epithelial sheet Cell polarity is essential to proper function Apical Domain Cell surface facing the lumen Apical domains contain specialized structures that add functionality: [lumen] Proteins (receptors, transporters, channels) [lumen] allow interaction with the lumen E.g. nutrients can be transported into the cell Other specializations increase surface area or help move substances along the epithelial surface Three important apical specializations are: Microvilli Cilia Stereocilia Microvilli Short, finger-like projections of uniform lumen length on the apical surface Enclosed by the plasma membrane E Significantly increases surface area Microvilli appear as individual structures in a TEM Present in cells specialized for absorption Red = plasma membrane! etc. Cytoplasm of cell Microvilli In a TEM, microvilli appear as individual structures Supported by actin filaments which insert into a network of cytoskeletal proteins referred to as the terminal web Glycocalyx can also be seen as a fuzzy border In the light microscope, microvilli can’t be resolved individually and instead look like the bristles of a soft brush Referred to as a “brush border” Cilia Longer, hair-like apical specializations Not as uniform in length Individual strands can be resolved in the light microscope Structure of cilia: Have an internal array of microtubules arranged in a regular pattern – one pair at the center and 9 pairs in a ring around them (“9 + 2” pattern) Specialized for motility – attached to the outer microtubule pairs are dynein motor proteins, which allow cilia to move E.g. Respiratory tract epithelia have cilia that flex (“beat”) to move fluid along their surface. Transports harmful particulate to places where it can be disposed Primary Ciliary Dyskinesia Recessive genetic disorder where ciliary microtubules lack dynein arms and are therefore non-motile In the respiratory system, cilia can’t clear mucus resulting in problems such as chronic sinusitis and bronchitis Since this is a genetic disorder, all cilia in the body are affected Some areas of the body that have cilia Stereocilia Specializations related to microvilli Have a core of actin filaments that attach to terminal web Longer, can branch Rarer – found in the epididymis and inner ear Epididymis – increase surface area Inner ear – components of special sensory cells Not motile Basal Domain Area opposite the apical domain. Important structures here may include: Basement membrane (BM) Hemidesmosomes – junctions that attach the cell to the BM Basal infoldings (striations) – the plasma membrane of the cell folds Do you recognize this organelle? Basement Membrane (BM) Acellular sheet of macromolecules that functions as: Structural support for epithelium and attachment site to lamina propria Semipermeable filter E.g. mutations in BM result in kidney disease, where filtration is compromised Important macromolecules of BM include collagen fibers, laminins, and integrin proteins Basal portion of cell BM appearance: H&E – acellular pink area in basal domain of bottom row of epithelium EM – resolves into two layers: Basal lamina – dense line. Base of epithelial cell is attached here, contains molecules that act as permeability barrier BM Reticular lamina – fibrous mesh that provides structure and attaches basal lamina to lamina propria BL = basal lamina; RL = reticular lamina; H = hemidesmosome; C = cell What is a Transmembrane Protein? Proteins that span the plasma membrane, and can interact with substances both inside and outside the cell Intracellular – inside the cell Extracellular – outside the cell Transmembrane protein Hemidesmosome Junction that function to: Attach the basal domain of the cell to the basal lamina Distribute force throughout epithelium, increasing structural integrity Consist of protein ‘plaques’ that anchor to structures in the following ways: Inside cell – intracellular plaque binds to intermediate filaments (keratin) of the cytoskeleton Outside cell – extracellular domains of integrins and laminins within the hemidesmosome bind to molecules in the basal lamina Lateral Domain Lateral domain notable as: Site of attachment to other cells in the epithelial sheet [lumen] Avenue of transport for materials (paracellular pathway) Proteins here form junctions that attach cells together and regulate transport. Junctions are classified into three functional groups: Occluding junctions – seals cells together, control transport of substances via paracellular pathway E.g. Tight junctions Adhering junctions – mechanically attaches cells together or to extracellular matrix E.g. Zonula adherens, macula adherens (desmosome) Communicating junctions – mediates passage of chemical or electrical signals from one cell to another E.g. Gap junctions  Occluding Junction Tight Junctions (Zonula Occludens) Tight junctions are important to cellular polarity and for the ability to constrict fluids with different chemical compositions to either side of epithelial sheet (selective permeability) Tight junctions form seals that: Prevent proteins from migrating to other domains E.g. apical channel proteins that bring nutrients in from the lumen cannot function properly if they migrate to the basal domain Limit transcellular transport E.g. a molecule transported through the cell can’t just diffuse back into the lumen through the lateral domain Found in the lateral domain adjacent to the apical surface Formed by transmembrane proteins claudin and occludin: Inside the cell they attach to actin filaments of the terminal web Outside the cell they bind to each other  Adhering Junction Zonula Adherens (ZA) Junctions that attach cells together and stabilize the sheet Forms a continuous belt (zonula) around the cell on the lateral surface Directly apposed in adjacent cells – plasma membranes are held together by cadherins: Outside the cell – extracellular domains of cadherins bind to one another Inside the cell – connects to actin filaments Found just below tight junctions  Adhering Junction Desmosomes (Macula Adherens) Form a series of attachment points (“spot welds”) that further stabilize epithelium Important in skin Abundant on the lateral surface, generally below tight junctions and zona adherens Desmosomes hold adjacent plasma membranes together by desmocollin and desmoglein proteins: Outside the cell, desmocollins and desmogleins of adjacent cells bind to each other Inside the cell, thick protein plaques serve as insertion points for intermediate filaments of the cytoskeleton In the blistering disease pemphigus, individuals make antibodies that bind to and disrupt desmosomes resulting in severe blistering of the skin Intermediate filaments Cell 1 Cell 2 Intracellular plaque Pemphigus blisters  Communicating Junction Gap Junctions Junctions that permit flow of ions and small molecules – allow for electrochemical communication between cells E.g. K+, Na+ and Ca2+ travel through gap junctions in heart muscle cells to allow the heart to contract in a coordinated fashion In lateral domain below tight junctions and ZA Consist of transmembrane connexin proteins that form channels between cells called connexons Six connexin proteins form one connexon Two connexons form a gap junction  Self Study Summary of Cellular Junctions Resources Ross and Pawlina, Histology: A Text and Atlas Chapter 4 – Tissues: Concept and Classification Chapter 5 – Epithelial Tissue Kierszenbaum & Tres, Histology and Cell Biology, Chapter 1, Epithelium Junqueira’s Basic Histology: Text and Atlas, Chapter 4, Epithelial Tissue