Histology Chapter 4

lamina propria

*The connective tissue that underlies the epithelia lining the organs of the digestive, respiratory, and urinary systems* -Most epithelia are adjacent to connective tissue containing blood vessels from which the epithelial cells receive nutrients and O2. - Even thick epithelia do not themselves normally contain blood vessels.

Brush Boarder

- In cells such as those lining the small intestine - densely packed microvilli are visible as a brush or striated border projecting into the lumen

stereocilia

- Long Microvilli - BUT less motile than microvilli, and may show branching distally. - specialized stereocilia with a motion-detecting function are important components of inner ear sensory cells.

hemidesmosomes

- On the basal epithelial surface, cells - attach to the basal lamina by anchoring junctions - adhesive structures resembling a half-desmosome ultra-structurally - BUT unlike desmosomes the clustered transmembrane proteins that indirectly link to cyto-keratin intermediate filaments are *integrins rather than cadherins*. The integrins of hemidesmosomes bind primarily to laminin molecules in the basal lamina.

unicellular glands

- Scattered secretory cells - common in simple cuboidal, simple columnar, and pseudostratified epithelia - e.g. goblet cell - abundant in the lining of the small intestine and respiratory tract, which secretes lubricating mucus that aids the function of these organs.

Microvilli

- absorption- apical cell surfaces - usually of uniform length - can increase surface area by 20- or 30-fold. - *thick glycocalyx* covering microvilli of the intestinal brush border - membrane-bound proteins and enzymes for digestion of certain macromolecules - *actin filaments* capped and bound to the surrounding plasma membrane by actin- binding proteins - dynamic microfilament arrays: undergo various myosin-based movements, which help maintain optimal conditions for absorption via numerous channels, receptors, and other proteins in the plasmalemma - actin filaments insert into the terminal web of cortical micro- filaments at the base of the microvilli.

basal bodies

- apical cytoplasmic structures just below the cell membrane - similar structure to that of centrioles, with triplets of microtubules and dynamic tubulin protofilaments forming rootlets anchoring the cilia to the cytoskeleton.

pemphigus vulgaris

- blistering (bullous) disease -involving the epidermis or stratified squamous epithelia of the oral mucosa: due to abnormal desmosome function caused by autoimmune reactions against specific desmogleins that reduce cell-to-cell adhesion. Similar dis- orders arise with genetic mutations for various junctional proteins.

axonemal dynein

- bound to one microtubule in each doublet - extend as "arms" toward a microtubule of the next doublet. - energy from ATP dynein-powered sliding of adjacent doublets relative to each other bends the axoneme and a rapid series of these sliding movements produces the beating motion of the cilium. - The long *flagellum* that extends from each fully differentiated sperm cell has an axonemal structure like that of a cilium and moves with a similar mechanism.

Mucous cells

- have RER and Golgi complexes and are filled apically with secretory gran- ules, but these contain *heavily glycosylated proteins* called *mucins*. - mucins hydrate upon released from the cell- form a layer of mucus: hydrophilic mucins are usually washed from cells during routine histological preparations, causing the secretory granules to stain poorly with eosin - Sufficient oligosaccharides remain in developing mucinogen granules, however, to allow mucous cells to be stained by the PAS method e.g. *goblet cells*

Endocrine glands

- lack myoepithelial cells - specialized for either protein or steroid hormone synthesis, w/ cytoplasmic staining characteristic of RER or SER, respectively. - proteins - exocytosis -lipophilic steroids -diffusion - involves hormone transport in the blood to target cells throughout the body - receptors may very close to the hormone-secreting cell or on the secreting cell itself, signaling which is termed *paracrine or autocrine*, respectively.

Cilia

- microtubules - most (if not all) other cell types have at least one short projection called a primary cilium, which is not motile but is enriched with receptors and signal transduction complexes for detection of light, odors, motion, and flow of liquid past the cells. - longer and two times wider thana typical microvillus - 9 + 2 assembly of microtubules is called an axoneme - *kinesin and cytoplasmic dynein* motors move along the peripheral microtubules for the transport of molecular components into and out of these structures. - continuous with those in basal bodies - exhibit rapid beating patterns that move a current of fluid and suspended matter in one direction along the epithelium: successive changes in the conformation of the axoneme

Epithelial Cell Polarity

- polarity with organelles and membrane proteins distributed unevenly within the cell - *basal pole* - the region of the cell contacting the ECM and connective tissue - *apical pole* - the opposite end, usually facing a space

focal adhesion/ focal contact.

- resembling hemidesmosomes superficially but smaller, more numerous, and consist of integrins linked indirectly to bundled *actin filaments, not intermediate filaments*. - linked via *paxillin to focal adhesion kinase*, a signaling protein which upon integrin binding to laminin or other specific ECM proteins initiates a cascade of intracellular protein phosphorylation affecting cell adhesion, mobility, and gene expression. - Focal adhesions are also important in migrating nonepithelial cells such as fibroblasts

Serous Cells

- synthesize proteins that are mostly not glycosylated, such as digestive enzymes. - have well-developed RER and Golgi complexes and are filled apically with secretory granules in different stages of maturation - stain intensely with basophilic or acidophilic stains. - Acini of the pancreas and parotid salivary glands are composed of serous cells.

Secretory Epithelia

-Epithelial cells that function mainly to produce and secrete various macromolecules may occur in epithelia with other major functions or glands. -May synthesize, store, and release *proteins* (eg, in the pancreas), *lipids* (eg, adrenal, sebaceous glands), or *complexes* of carbohydrates and proteins (eg, salivary glands). * Epithelia of mammary glands secrete all three substances. * some glands (eg, sweat glands) have little synthetic activity and secrete mostly water and electrolytes (ions) trans- ferred from the blood.

Functions of Basement Membranes

-filters - structural support for epithelial cells - attach epithelia to underlying connective tissue - *Basal lamina* components help organize *integrins* and other proteins in the plasma membrane of epithelial cells, maintaining cell polarity and helping to localize endocytosis, signal transduction, and other activities. - mediate many cell-to-cell interactions involving epithelia and mark routes for certain cell migrations along epithelia. - serves as a scaffold that allows rapid epithelial repair and regeneration.

types of exocrine secretion mechanisms

1. Merocrine secretion: This is the most common method of protein or glycoprotein secretion and involves typical exocytosis from membrane-bound vesicles or secretory granules. 2. Holocrine secretion: Here cells accumulate product continuously as they enlarge and undergo terminal differ- entiation, culminating in complete cell disruption which releases the product and cell debris into the gland's lumen. This is best seen in the sebaceous glands producing lipid- rich material in skin 3. Apocrine secretion: Here product accumulates at the cells' apical ends, portions of which are then extruded to release the product together with small amounts of cyto- plasm and cell membrane. Lipid droplets are secreted in the mammary gland in this manner

merocrine secretion categories

1. serous 2. mucous 3. Seromucus

Parts of the Basement Membrane

1.) Basal lamina - closest layer to epithelium (type IV collagen, fibers, *laminin* (major glycoprotein (b)), proteoglycans, glycoproteins) 2.) Reticula layer - Type III collagen fibers secreted by underlying connective tissue. Absent in some epithelial membranes.

carcinomas & adenocarcinomas

Both benign and malignant tumors can arise from most types of epithelial cells. Malignant tumors of epithelial origin are called *carcinomas* (Gr. karkinos, cancer + oma, tumor). Malignant tumors derived from glandular epithelial tissue are called *adenocarcinomas* (Gr. adenos, gland + karkinos). Adenocarcinomas are by far the most common tumors in adults after age 45.

Epithelia

Epithelial tissues are composed of closely aggregated *polyhedral cells* adhering strongly to one another and to a thin layer of ECM, forming cellular sheets that line the cavities of organs and cover the body surface. *Epithelia (Gr. epi, upon + thele, nipple) line all external and internal surfaces of the body and all substances that enter or leave an organ must cross this type of tissue.*

RENEWAL OF EPITHELIAL CELLS

Epithelial tissues are relatively labile structures whose cells are renewed continuously by mitotic activity and stem cell populations. The rate of renewal varies widely; it can be fast in tissues such as the intestinal epithelium, which is replaced every week, or slow, as in the large glands. In stratified epithelial tissues, stem cells and mitosis occur only within the basal layer in contact with the basal lamina. In some functionally complex epithelia, stem cells are located only in restricted niches some distance from the transit amplifying cells and differentiating cells. For example, the epithelium lining the small intestine is derived completely from stem cells found in the simple glands between the intestinal villi. In the epidermis, many stem cells are located at a characteristic position along the wall of hair follicles.

Helicobacter pylori

Important in the etiology of gastric ulcers, binds the extracellular domains of tight-junction proteins in cells of the stomach and inserts a protein into these cells, which targets ZO-1 and disrupts signaling from the junction.

myoepithelial cells

In addition to secretory cells, epithelia of many exocrine glands (eg, sweat, lachrymal, salivary, and mammary glands) contain contractile *myoepithelial cells* at the basal ends of the secretory cells. Long processes of these cells embrace an acinus. Bound to the basal lamina by hemidesmosomes and connected to the other epithelial cells by both gap junctions and desmosomes, myoepithelial cells are rich in actin filaments and myosins. Strong contractions in these cells serve to help propel secretory products from acini into the duct system.

transcytosis

In thin cells with few organelles, the simple squamous epithelial cells lining blood and lymphatic capillaries (endothelia) or body cavities (mesothelia), which cross the thin cells in both directions and release their contents on the opposite side by exocytosis. This process of *transcytosis* also occurs between the apical and basolateral membranes domains in cells of simple cuboidal and columnar epithelia and is important in many physiologic processes.

parenchyma and the stroma

Most organs can be divided into the parenchyma, which is composed of the cells responsible for the organ's specialized functions, and the stroma, the cells of which have a supporting role in the organ. Except in the brain and spinal cord, the stroma is always connective tissue

neoplasia & metaplasia

Some epithelial cells are prone to abnormal growth or dysplasia, which can progress to precancerous growth called *neoplasia*. Early neoplastic growth is often reversible and does not always result in cancer. Under certain abnormal conditions, one type of epithelial tissue may undergo transformation into another type in another reversible process called *metaplasia*. In heavy cigarette smokers, the ciliated pseudostratified epithelium lining the bronchi can be transformed into stratified squamous epithelium *dysplasia* - abnormal growth, bad cancer irreversible

transcellular transport

Some epithelial cells specialize in the transfer of ions (by ion pumps) and water (via the membrane channels called aquaporins) in either direction across the epithelium, the process known as transcellular transport. *Apical tight junctions* prevent paracellular diffusion or back- flow between the cells. Epithelia of kidney tubules are key sites for ion and water transport, maintaining the body's overall balance of salts and water. Cells of the proximal renal tubules are spe- cialized structurally for transcellular transport.

seromucous glands

Some salivary glands have both serous acini and mucous tubules with clustered serous cells. The product of such glands is a mixture of digestive enzymes and watery mucus.

papillae

The area of contact between the two tissues (epithelia & lamina propria) may be increased by small evaginations called *papillae* (L. papula, nipple) projecting from the connective tissue into the epithelium. *Papillae occur most frequently in epithelial tissues subject to friction, such as the covering of the skin or tongue.

Clostridium perfringens

The enterotoxin secreted by Clostridium perfringens, which causes "food poisoning," binds claudin molecules of intestinal cells, prevents insertion of these proteins during maintenance of tight junctions, and causes loss of tissue fluid into the intestinal lumen via the paracellular pathway.

acne vulgaris

The holocrine sebaceous glands are the primary structure involved in the common form of acne, acne vulgaris. Excessive holocrine secretion of sebum and keratin triggered by the surge of the steroid hormone testosterone that occurs in both genders at puberty frequently leads to blocked ducts within the gland. Activity of the normal commensal skin bacterium Propionibacterium acnes within the blocked duct commonly produces localized inflammation.

reticular lamina

The more diffuse meshwork of the reticular lamina contains *type III collagen* and is bound to the basal lamina by *anchoring fibrils of type VII collagen*, both of which are produced by cells of the connective tissue

chronic bronchitis

common among habitual smokers, the number of goblet cells in the lining of airways in the lungs often increases greatly. This leads to excessive mucus production in areas where there are too few ciliated cells for its rapid removal and contributes to obstruction of the airways. The ciliated pseu- dostratified epithelium lining the bronchi of smokers can also be transformed into stratified squamous epithelium by metaplasia.

TYPES OF EPITHELIA

covering (or lining) epithelia and secretory (glandular) epithelia

chronic vitamin A deficiency

epithelial tissues of the type found in the bronchi and urinary bladder may gradually be replaced by stratified squamous epithelium.

Celiac disease

gluten-sensitive enteropathy or sprue, is a disorder of the small intestine in which one of the first pathologic changes is *loss of the microvilli brush border* of the absorptive cells. This is caused by an immune reaction against the wheat protein gluten during its digestion, which produces diffuse enteritis (intestinal inflammation), changes to the epithelial cells leading to malabsorption, and eventually to pathologic changes in the intestinal wall. The malabsorption problems and structural changes are reversible when gluten is removed from the diet.

external laminae

similar composition to basal lamina - exist as sleeves surrounding muscle cells, nerves, & fat-storing cells, where they serve as semipermeable barriers regulating macromolecular exchange between the enclosed cells and connective tissue.

ECM components of the Basal Lamina

■ *Type IV collagen:* Monomers of type IV collagen self- assemble into a two-dimensional network of evenly spaced subunits. ■*Laminin:* These are large glycoproteins that attach to trans-membrane proteins called integrins at the cells' basal surface and project through the network of type IV collagen. ■ Nidogen and perlecan: Respectively a short, rod-like protein and a proteoglycan, both of these cross-link laminin to the collagen network and help determine the porosity (porous) of the basal lamina and the size of molecules able to filter through it.

principal functions of epithelial tissues

■Covering, lining, and protecting surfaces (eg, epidermis) ■ Absorption (eg, the intestinal lining) ■ Secretion (eg, parenchymal cells of glands