Histology: Epithelium

Apocrine glands

(e.g. lactating mammary gland) part of the apical cytoplasm of the secretory cell is released along with the contents.

Holocrine glands

(e.g. sebaceous gland), the entire secretory cell along with its contents is released.

Exocrine

- secrete into duct and stains with PAS

Zonula Occludens (Gap junction)

--> Contain electronic and metabolic connection with plaque-like array of subunits --> Not part of junctional complex and is common in certain tissues other than epithelia (e.g. central nervous system, cardiac muscle and smooth muscle) --> Gap junctions couple adjacent cells metabolically and electrically --> Gap junctions is a plaquelike entity composed of an ordered array of subunits called connexons, which extend beyond the cell surface into the gap to keep the opposing plasma membranes approximately 2 nm apart. --> Connexons consist of 6 cylindrical subunits (composed of proteins called connexins) which are arranged radially around a central channel with a diameter of 1.5 nm. --> Precise alignment of connexons on adjacent cells produces a junction were cell-to-cell channels permit passage of ions and small molecules with a molecular weight of less than 1200 daltons. --> Connexons may alter their conformation to shut of communication between cells.

Microvilli

--> Fingerlike projections of epithelium that extend into lumen and increase absorptive surface area --> Characterized by glycocalyx (sugar coat) on their exterior surface, formed by branching oligosaccharides of integral membrane proteins and phospholipids --> Actin filaments longitudinally arranged extend into cell to form terminal web at apical cytoplasm --> Microvilli constitute the brush border of kidney proximal tubule cells and the striated border of intestinal absorptive cells. --> Location of microvilli will say where on apical domain endo and excocytosis will take place --> Anchored to villin (tip of microvilli), terminal web composed of actiin filaments (presence of myosin II + tropomyosin) to give contractile ability and decrease apical surface diameter to spread microvilli

Macula Adherens (desmosomes)

--> Small, discrete disc-shaped adhesive site. --> Also found at sites other than the junctional complex, where it joins epithelial cells. --> it is characterized by a dense plaque of intracellular attachment proteins, called desmoplakins, on the cytoplasmic surface of each opposing cell. --> Keratin intermediate filaments in bundles (tonofilaments) loop into and out of the dense plaque from the cytoplasm. --> Between the adjacent cells are transmembrane linker glycoproteins, called desmogleins and desmocollins that are cadherin molecules. --> Intercellular space between cells have dense material/ striations that are transmembrane linkers --> E-cadherins and desmogleins makeup thick electron density btw membranes --> Used in epidermis to keep cells together and prevent water loss --> Hold intercalated discs together

Transitional (urinary) epithelium

--> Stratified superficial cells --> Relaxed state: Dome shape bulge into lumen (8 layers below) • Could have two nuclei (binucleated) prepared to divide fast with many tight junctions --> Stretched state: flat and reduced to 2 layers below --> Lines excretory pathways from renal calyces to urethra in urinary system

Lateral modifications

--> These surfaces contain specialized junctions that provide adhesion between cells and restrict movement of materials into and out of the lumina. --> The junctional complex is an intricate arrangement of membrane-associated structures that functions in cell-to-cell attachment of columnar epithelial cells. --> It corresponds to the terminal bar observed in epithelia by light microscopy and consists of three distinct components that are visible by electron microscope

Zonula occludens (tight junctions)

--> Zone that surrounds the entire apical perimeter of adjacent cells and is formed by fusion of the outer leaflets of the cells' plasma membranes --> In freeze-fracture preparations, tight junctions are visible as a branching anastomosing network of intramembrane strands on the plasma membrane inner leaflet next to the cytoplasm (P-face) and grooves on the corresponding external E-face the inner aspect of the outer leaflet. --> Strands of transmembrane proteins (claudins and occludens) that link adjacent plasma membranes (thus sealing off the intercellular space) --> Tight junctions prevents movement of substances into the intercellular space from the lumen. This ability (its tightness) is directly related to the number and complexity of the intramembrane strands. --> Tight junction is analogous to fasciae occludens (ribbon-like area of fusion between transmembrane proteins on adjacent endothelial cells lining capillaries.) --> # of strands (in apical to basal direction) + presence of channels determine leakiness of the jxn

Zonula Adherens (Intermediate junction)

--> Zone that surrounds the entire perimeter of epithelial cells just basal to the tight junction. --> Extends completely around the perimeter of epithelial cells as adhesive and structure supporting --> Terminal Web - Opposing plasma membranes are reinforced by actin filament meshwork --> A mat of actin filaments is located on each of its cytoplasmic surfaces. The actin filaments are linked, via alpha-actinin and vinculin to the transmembrane glycoprotein E-cadherin. --> E-cadherin glycoprotein relies on Ca2+ for adhesion or to join the two membranes. --> It is analogous to fasciae adherens (ribbon-like adhesion zone in intercalated disks of cardiac muscle)

Hemidesmosomes

--> present in lowest basal layer of cells and attaches basal layer to basal lamina --> Function in mediating the adherence of epithelial cells to the underlying basal lamina. --> Incomplete desmosome only about half of a desmosome (use integrin proteins and tonofilaments to attach) --> These junctions are present on the basal surface of basal cells in certain epithelia (e.g. tracheal epithelium and stratified squamous epithelium and on myoepithelial cells, where they lie adjacent to basal lamina). --> Consist of dense cytoplasmic plaque, which is linked via transmembrane receptor proteins (integrins) to lamins in basal lamina --> Anchoring filaments (type VII collagen) from the basal lamina extend deeper into the underlying connective tissue and insert into plaques of type IV collagen. --> Keratin filaments (tonofilaments) in the cell terminate in the hemidesmosome plaque, allowing these junctions to link the cytoskeleton with the extracellular matrix --> May infect and separate from basal lamina causing fluid to collect (Bollus) --> IgG immunoglobulins (antibodies) and activated T lymphocytes (WBC) attack components at basement membrane specific to desmosomes --> Auto-antibodies bind and eosinophils release protease to degrade hemidesmosome

Basal Lamina

-->Basal Lamina - extracellular supportive structure 20 to 100 nm thick that is visible only by electron microscopy. --> It is produced by the epithelium resting upon it and is composed mainly of Type IV collagen, lamin (which does not stain with H/E), entactin, and proteoglycans (rich in heparin sulfate and stains with H/E) --> Consists of two Zones (Both produced by epithelium): • Lamina Rare (lamina lucida) - low density lying next to plasma membrane of basal cells • Lamina Densa - dense meshwork of type IV collagen, glycoproteins, and glycoaminoglyans which lies adjacent to reticular lamina of the deeper connective tissue. o Reticular Lamina - produced by connective tissue (referred to as reticular fibers) --> The basal lamina plus the underlying reticular lamina constitute the basement membrane, which is observed only with light microscopy. --> Fused basal lamina - epithelium are not always up against connective tissue and may fuse with basal lamina in another cell o Lungs - cell rests directly against basal lamina of blood cells o Will not stain do to laminin and do not contain reticular fibers

Lateral interdigitations

-> fingerlike projections that interlock adjacent epithelial cells (lock & key) --> Absorb water from lumen directly and accumulate stain in area of water absorption (looks like cell wall but is not) --> Found in collecting duct of kidney, gallbladder for water control, or colon

Columnar cells

-> most active cell as of division, absorption, and secretion (oval nucleus at base) --> Many times the nucleus is euchromatic and many vesicles can be seen in the cell A) Simple --> Consists of polyhedral cells (elongated in one plane) --> Lines the stomach, intestine, and excretory ducts of many glands --> Contains large gaps that allow for folding in intestine when it is stretched Major function: Absorption conduit barrier, absorption and secretion B) Stratified Columnar - rare to find --> Found in large excretory ducts of some glands and in cavernous urethra

Endocrine glands

1) secrete into blood stream and lack ducts - secretion called hormone 2) Found in the parenchyma of gland while connective tissue makes up stroma 3) May be unicellular (e.g. individual endocrine cells in GI and respiratory epithelia) or multicellular (e.g. adrenal gland) and they lack a duct system. 4) In multicellular glands, secretory material is released into fenestrated capillaries, which are abundant just outside of the basal lamina of the glandular epithelium. --> Enteroendocrine cells in gastrointestinal - unicellular Respiratory epithelia - multicellular • Basal lamina sep. epithelium from connective tissue compartment • Blood vessels do not penetrate basal lamina

Discuss the 4 basic tissue types

A) Epithelial Tissue B) Connective Tissue C) Muscle Tissue D) Nervous Tissue

Epithelium Function

Absorption occurs via endocytosis or pinocytosis in various organs (e.g. the proximal convoluted tubule of the kidney) Secretion of various molecules (eg hormones, mucus, proteins) occurs by exocytosis Selective permeability results from the presence of tight junctions between epithelial cells and permits fluids with different compositions and concentrations to exist on separate sides of an epithelial layer (e.g. intestinal epithelium) Protection from abrasion and injury is provided by the epidermis, the epithelial layer of skin.

Describe immotile cilia syndrome and its clinical manifestations in the form of Kartagener's syndrome

Cilia are present in almost all organs and play a significant role in the human body. There is increasing evidence that cilial dysfunction is involved in many human disorders. Several disorders called immotile cilia syndrome affect the function of cilia. Mucociliary transport that occurs in the respiratory epithelium is one of the most important mechanisms protecting body against invading bacteria and other pathogens. Motile cilia covering the epithelium of the respiratory tract are responsible for the clearance of the airway. Failure of the mucociliary transport system occurs in Kartagener's syndrome. Kartagener's syndrome caused by structural abnormality that results in absene of dynein arms. Also misoriented basal feet pointing in different directions.

How glands are classified

Class. # cells, type of duct, shape of glandular unit, type & mode of secretion

Classify the types of epithelial tissues and give examples of sites where each may be found. State a minimum of five different functions of various types of epithelia.

Classified into types by the number of cell layers and the shape of the superficial layer of cells. 1) Squamous (flat) 2) Cuboidal (square) 3) Columnar (rectangle) • Simple: One cellular layer all in contact with basement membrane • Stratified: Only one layer actually touches the basement membrane while all others rest in rows atop

Exocrine gland divisions

Connective tissue may divide exocrine gland into lobes or smaller lobules and locations of ducts can be: • Interlobar - between lobes, interlobular - between lobules, intralobar - within lobe • Intralobular - single lining of epithelium with more pathways to get to main duct • Striation or Intercalated Interlobular - stratified columnar secrete directly into the duct

Describe the changes in the hemidesmosomes which may lead to bullous (vesicular) lesions (as seen in bullous pemphigoid)

Describe the changes in the hemidesmosomes which may lead to bullous (vesicular) lesions (as seen in bullous pemphigoid)

Changes in epithelium resulting in metaplasia and carcinoma

Epithelia undergo metaplasia in response to persistent injury. Metaplasia is the conversion of one type of differentiated epithelium into another. Most commonly, a glandular epithelium is transformed into a squamous epithelium. In cases of chronic acid reflux from the stomach into the lower esophagus, the stratified squamous nonkeratinized epithelium is replaced by glandular mucus-secreting epithelium (Barrett epithelium) similar to that found lining the cardia of the stomach. This helps protect the esophagus against injurious effects of the acid and pepsin but is also a well-known precursor of esophageal adenocarcinoma. Epithelial cell tumors Occur when cells fail to respond to normal growth regulatory mechanisms. 1) These tumors are benign when they remain local 2) They are malignant when they invade neighboring tissues. Then, they may (or may not) metastasize to other parts of the body. A) Carcinomas--> malignant tumors that arise from surface epithelia B) Adenocarcinomas--> malignant tumors that arise from glands.

Describe the clinical significance of the junctional complexes as a target of pathogenic agents (as seen in pemphigus vulgaris).

Epithelium form a physical barrier that allows the body to maintain internal homeostasis while protecting the organism from harmful pathogenic agents from the external environment. The easiest way for many viruses, bacteria, and parasites to successfully compromise the protective functions of the epithelial layer is to destroy the junctional complexes between epithelial cells. Several proteins found in junctional specializations of the cell membrane are affected by molecules produced or expressed by these pathogenic agents.

Basal plasma membrane infoldings

Form deep invaginations that compartmentalize mitochondria --> A common specialization in ion transporting epithelia (e.g distal convoluted tubule of kidney, striated ducts in salivary glands) --> Form deep invaginations that compartmentalize mitochondria --> They increase surface area and bring ion pumps (Na+-K+ ATPase) in the plasma membrane close to their energy supply produced in the mitochondria

Stratified squamous epithelium (keratinized)

Keratinized • Flattened superficial layer of cells do not contain a nucleus and become filled with keratin (dead) • Constitutes epidermis - skin • Cells below progress upward losing more and more components of their cell

Merocrine glands

Merocrine glands (e.g. parotid gland) the secretory cells release their contents by exocytosis.

Multicellular gland

Multicellular - gland composed of more than one cell. • Classification of multicellular glands is based on 2 criteria: • Multicellular glands are classified according to duct branching as simple glands (duct does not branch) or compound glands (duct branches) • They are further classified according to the shape of the secretory unit as acinar or alveolar (saclike or flasklike) or tubular (straight, coiled or branched) • A connective tissue capsule may surround the gland or septa of connective tissue may divide the gland into lobes and smaller lobules. • Glands may have ducts between lobes (interlobar), within lobes (intralobar), between lobules (interlobular) or within lobules (intralobular), such as striated and intercalated ducts.

Stratified squamous epithelium (non-keratinized)

Non keratinized (Wet) • Composed of several layers of cells all containing a nucleus (Most protective form of epithelium) • Lines the moist body surfaces of mouth, esophagus, and vagina Keratinized • Flattened superficial layer of cells do not contain a nucleus and become filled with keratin (dead) • Constitutes epidermis - skin • Cells below progress upward losing more and more components of their cell Location of stratified squamous epithelium: 1) Epidermis 2) Oral cavity and esophagus 3) Vagina Function: Barrier, protection

Glands

Originate from epithelium that penetrates the connective tissue and forms secretory units. Structure A gland consists of a functional portion (parenchyma) of secretory and ductal epithelial cells, which is separated by a basal lamina from supporting connective tissue elements (stroma). Glandular Epithelium - Secretory portions

Simple squamous epithelium

Simple - consists of single layer of flattened cells Location of simple squamous epithelium: Vascular system (endothelium) Body cavities (mesothelium) Bowman's capsule (kidney) Respiratory spaces in lung Major functions: Exchange, barrier in central nervous system. Exchange and lubrication Barrier Exchange

Duct

Simple - unbranched duct o Compound - branched duct • Shape of secretory unit- either acinar (saclike) or tubular (straight, coiled, branch) • Type of secretion (one or both) o Serous - watery and rich in enzymes (Stains with H/E) • Contain a lot of RER for active secretions and zymogen granules (pre-enzyme form near golgi) • Parotid gland - only contains serous secretory unitsa o Mucous - viscous liquid that protects or lubricates (very light purple PAS) Highly glycosylated • Sublingual gland - contains both pure mucous and mixed secretory units Parotid gland - only contains serous secretory units Submandibular gland - both pure serous and mixed secretory units - in routine tissue prep, serous cells more removed from lumen of acinus and are shaped as crescent cells (demilunes) at periphery of mucus acinous = artifact

Squamous Epithelium

Squamous Epithelium - little to no activity used for protection with flat nucleus

Apical epithelial surfaces

These surfaces may possess specialized structures such as microvilli, stereocilia, and cilia.

Epithelium Function

Transcellular transport of molecules from one epithelial surface to another occurs by various processes, including the following: 1) Diffusion of oxygen and carbon dioxide across the epithelial cells of lung alveoli and capillaries 2) Carrier protein-mediated transport of amino acids and glucose across intestinal epithelia 3) Vesicle-mediated transport of immunoglobulin A (IgA) and other molecules

Unicellular gland

Unicellular glands- composed of a single cell (e.g. goblet cells in tracheal epithelium) Goblet Cell (usually flat nucleus pushed down for more mucous)

Cilia

actively motile extensions that transport substance across surface (in bronchial, tracheal, oviduct epithelium) -contain a core of longitudinally arranged microtubules (the axoneme) which arises from a basal body during ciliogenesis.

Cilia (axoneme)

core of nine doublet microtubules with (9+2 configuration) 9 pairs of doublets circular and two in the middle A) Ciliary dynein arms extend unidirectionally from one member of each doublet microtubule and interact with adjacent doublets, so that they slide past one another. B) These arms consist of ciliary dynein, which a head that is an ATPase that splits ATP to liberate the energy necessary for active movement of a cilium. C) Radial spokes extend from each of the nine outer doublets toward the central sheath. D) Central sheath surrounds the two central microtubules; it and the radial spokes regulate the ciliary beat. E) Nexin an elastic protein that connects adjacent doublet microtubules and helps maintain the shape of the cilium. F) Basal body cylindrical structure at the base of each cilium that consists of 9 triplet microtubules arranged radially in the shape of a pinwheel (9+0 configuration) G) Basal body resembles a centriole but has a less complex central organization. The inner two triplets of the basal body give rise to the doublet microtubules of the cilium axoneme.

Paracrine

into extracellular space

Terminal bar

junctional complex: encircle every cell like ring of six pack can soda): ZO, ZA, MA/Desmosome - separating membranes further down you go

Stereocilia

long microvilli not cilia in the epididymis and vas deferens of the male reproductive tract.

Nucleus

o Euchromatin - DNA is unwound, stain is irregular, and nucleolus is visible (nucleus is active) o Heterochromatin - chromatin is condensed and stains very dark (not active)

Histology pathologies

o Kartagener's Syndrome - autosomal recessive disorder in genes that code tubulin and dynein (ciliary protein) Immotile cilia cannot clear mucous causing recurrent pulmonary infections or sterility in males Situs inversus - organ reversal due to faulty migration during embryogenesis PCD - Primary Ciliary Dyskinesia + situs inversus = KS o Bullous Pemphigoid - Bullae means enlarged fluid filled vesicle Autoimmune skin disease where forms blisters between dermis and epidermis IgG antibodies + act. T cells attack components of basement membrane specific to hemidesmosomes, IgG bind and stimulate infiltration, eosinophils release proteases that degrade hemidesmosome leads to fluid accumulation o Metaplasia - reversible change of one adult epithelium with another due to stimulus o Carcinoma - malignant neoplasms of epithelial cell origin (neoplasm is just a tumor) Lesion can invade adjacent structures and spread to distant sites (metastasize) Adenoma: Benign neoplasm producing gland pattern and to those derived from glands

Multicellular glands

secrete various substances • -Mucous is a viscous material that usually protects or lubricates cell surfaces • -Serous secretions are watery and often rich in enzymes • -Mixed secretions contain both mucous and serous components Mechanisms of secretion vary:

Structural and functional characteristics that distinguish epithelium from other tissues

• Avascular: no blood vessels (protected by the basement membrane [produced by epithelial and connective tissue] - blood vessels in connective tissue) • Polarized epithelial cells specialized to perform a variety of vectorial functions o Functional & morphological polarity: apical, lateral, basal domain o Organelles are reflected of the function of a cell at a particular time and change often o Number of nuclear pores on a nucleus is reflective of activity level o Rough Endoplasmic reticulum is attached to nucleus if actively translating

Basal membrane

• Basal membrane is a very selective layer and biochemistry changes according to needs of a cell (layer of cells touching basement membrane) • Cells lining the lumen determine cell type - may be different at basement membrane but named according to lumen type 1. Very healthy cells next to basal membrane, right next to food supply and take up most stain 2. Nucleus shape is important - when dyed the shape of the cell is unknown only the nucleus is visible

Cuboidal cells

• Cuboidal - nucleus is round and spherical in center of square cell good for intermediate activity o Simple --> Lines distal tubules of kidney, follicles in the thyroid gland, and surface of the ovary o Stratified - uncommon --> Lines the duct of sweat glands

P-face versus E-face

• P-Face (Proteoplasmic) - inside the cell • E-Face (External) - outside of cell

Pseudostratified epithelium

• Pseudostratified - Respiratory Epithelium --> Not actually stratified instead it is simple - seems that way because nuclei are dispersed --> All cells touch the basal lamina, but do not touch the lumen --> Some contain mucous secreting goblet cells --> Lines the trachea, primary bronchi, and excretory ducts in parotid gland --> Epididymis - pseudostratified columnar with stereocilia

Explain the staining properties exhibited by various parts of the cells in relation to hematoxylin and eosin stains.

• Staining o Acids such as nucleic acids in nucleus (basophilic components) Hemotaxyllin - dark blue to purple and is very basic o Bases such as proteins (acidophilic components - acid loving) Eosin - Pink to red and is very acidic o Carbohydrates such as glycogen, glycoproteins, and glycoaminoglycans Periodic Acid Schiff (PAS) o Fat - Osmium Tetroxide with Oil Red (metal with high affinity) or Sudan Black/ Red o Connective Tissue - Trichome o Reticular fibers- silver stain

Define epithelial tissue

• The tissue that lines internal and covers external surface of body • Specialized for different functions such as absorption (microvilli), secretion (excocytosis), transport (basofolds), protection (keratinized outer layer of skin), sensory (receptors for smell, taste, vision, hear) • Cells lie close to each other with little intracellular space • Composed of one cell layer (simple) or more than 1 cell layer (stratified) • Is avascular • Separated from underlying connective tissue by basement membrane • These cells have distinct biochemical, functional and structural domains that confer polarity or sidedness to epithelia.