Tetiana Haniastuti, Ph.D

The oral mucosa is the mucous membrane lining the inside of the mouth and consists of stratified squamous epithelium termed oral epithelium and an underlying connective tissue termed lamina propria.[

Lapisan yang melapisi bagian dalam mulut yang dilapisi oleh epitel pipih berlapis yang dibawahnya terdiri dari jaringan ikat dan lamina propria

The two main tissue components of the OM are:• The oral epithelium, it is a stratified squamous epithelium• The lamina propria, it is the underlying connective tissue.

The interface between oral epithelium and lamina propria (basement membrane) is usually irregular and the so called connective tissue papillae interdigitate with the epithelial ridges.

The tissue component under the oral mucosa is the submucosa and it is less easy to recognize the junction between them than between oral epithelium and lamina propria.

• It is derived from the embryonic ectoderm and forms the primary barrier between oral environment and underlying tissues.

• It consists of stratified squamous cells arranged in 4 distinct layers

• A=stratum germinativum (basal layer);

• B=stratum spinosum (prickle cell layer);

• C=stratum granulosum (granular layer);

• D=stratum corneum (keratinised or cornified layer)

The cells of oral epithelium that take part in the renewal are:• Progenitor cells: the function is to divide and provide

new cells• Maturing cells: they undergo a process of maturation to

form the protective cell layer.

It maintains its continuity by a continuous cell renewal:

• Cell proliferation : dilakukan oleh proliferasi sel

• Cell maturation : setelah proliferasi lalu melakukan maturasi untuk membentuk lapisan paling atas

Selalu mempertahankan continuitas atau memperbaharui diri melalui : Maturasi dan proliferasi

The progenitor cells are located in the basement membrane in thin epithelia (floor of the mouth) and in the lower two to three cell layers in thicker epithelia (cheek)

Progenitor cells divide into new progenitor cells or into maturing cells.

Letaknya di atas membrana basalis, terletak pada lapisan sel basal, sel pada stratum basal menunjukkan aktivitas mitosik paling tinggi, cenderung berkelompok.

• The cells of the st. basale shows the highest mitotic activity.• This maturation results in keratinization or non-keratinization • These basal cells tend to cluster and are more frequently found at the

bottom of the retes of the epithelium

• inner most layer• cuboidal or columnar cells• in the thin mucosa of the floor

of the mouth = 1 layer• Pada mukosa yang tipis = hanya

1 lapis sel basal• in the cheeks and palate = 2 or 3

layers (pada pipi atau palatum, bisa 2 atau 3 lapis)

• also called stratum basale because it attaches firmly to the basal lamina of the basement membrane (disebut stratum basal karna melekat pada lamina basal pada dasar membran.

• contain progenitor or stem cells = produce the basal cells that mature into all cells of the epithelium

Basal layer or stratum germinativum

Diagram depicting the compartments of the oral epithelium and indicating the statistical basis of a homeostatic system, that is, after mitosis one cell remains in the reproductive compartment while the other moves into the functional compartment.

A. Ian Hamilton And H. J. J. Blackwood J. Anat. (1974), 117, 2, Pp. 313-327

Di epitel ga ada pembuluh darah ya, jadi pembuluh darah itu di lamina propria jadi metabolisme nya berasal dari lamina propria. Stratum basal itu = reproductive compartment sedangkan yang stratum di atasnya itu = functional compartment

Epithelium of the cheek showing the constituent cell layers and compartments.

A. Ian Hamilton And H. J. J. Blackwood J. Anat. (1974), 117, 2, Pp. 313-327

• Lies above the first one and contains several rows of elliptical or spherical cells.

• Di superfisial stratum basal, terdiri dari beberapa lapisan

• from maturation and migration of basal cells • several layers thick• Both, st. basale and st. spinosum, together

constitute half to two third of the thickness of the oral epithelium. (1/2 -2/3)

• The cells have cytoplasmatic processes that have contact with other processes of other cells. connected by bundles of intermediate filamentsmelanocytes are common

• Langerhans cells also found – in the more superficial layers of the prickle layer

• Sel-sel memiliki proses cytoplasmatic yang memiliki kontak dengan proses lain dari sel-sel lain. dihubungkan dengan bundel filamen menengah melanosit yang umum. Sel Langerhans juga ditemukan - di lapisan lebih dangkal dari lapisan merinding

prickle layer = stratum spinosum

As cells leave the basal layer and enter into differentiation, they become larger and begin to flatten and accumulate cytoplasmic protein filaments, representing the cytokeratins. Terdapat akumulasi filamen sitoplasmic yang merupakan representasi sitokeratin.

As the cells enter the prickle cell layer, small organelles known as membrane-coating granules representing accumulating lipid become evident . Trus ada granula yang melapisi membran dan mengandung lipid

In addition to the accumulation of lipids and keratins, the differentiating keratinocytes synthesize and retain a number of specific proteins, including profilaggrin, involucrin, and other precursors of the thickening of the cell envelope .

• The granular layer - stratum granulosum - is the next layer and consists of larger flattened cells containing small granules. Lebih memipih dan ada granula yang lebih kecil lagi.

• made up of epithelial cells displaced from the prickle

• in keratinized epithelium – cell synthesize large quantities of proteins (including keratin) – cytoplasm appears granular

• the granules = keratohyalin granules• these granules surround the keratin

filaments as they develop• as keratin is made – cells become thinner

and flatter• the plasma membrane thickens and

becomes less permeable (plasma membran akan menebal dan kurang permeable)

• the cells then die and dehydrate creating bundles of keratin surrounded by keratohyalin sandwiched between two phospholipid membranes. sel kemudian mati dan dehidrasi menciptakan bundel keratin dikelilingi oleh keratohyalin terjepit di antara dua membran fosfolipidi

granular layer = stratum granulosum

Differentiation in keratinized epithelia leads to production of the stratum corneum.

The cornified cells making up this layer are flat and hexagonal in shape, filled with a compact array of condensed cytokeratin filaments, bounded by a thickened cell envelope, and surrounded by an external lipid matrix.

keratinized layer/superficial layer = stratum corneum

At the boundary between the granular and cornified layers, the membrane-coating granules migrate to the superficial (apical) aspect of the keratinocyte, where the bounding membrane of the organelle fuses with the cell plasma membrane so that the lipid lamellae are extruded into the extracellular spaces of the surface layer . Thus, the membrane-coating granules are believed to be responsible for the formation of a superficial, intercellular, permeability barrier in stratified squamous epithelium.

After the granules are extruded, the interior of the cell becomes filled with aggregated cytokeratin filaments, and involucrin, loricrin, and other proteins are deposited on the inner aspect of the plasma membrane as a thick band of protein that becomes covalently cross-linked.

Dengan demikian, granul membran-lapisan yang diyakini bertanggung jawab untuk pembentukan dangkal, antarsel, permeabilitas barrier epitel skuamosa berlapis.Setelah butiran yang diekstrusi, bagian dalam sel menjadi penuh dengan filamen cytokeratin agregat, dan involucrin, loricrin, dan protein lain yang disimpan pada aspek dalam dari membran plasma sebagai band tebal protein yang menjadi kovalen cross-linked.

keratinized layer/superficial layer = stratum corneum

Pada stratum granulosum ada granula keratohyalin, kalau ada diferensiasi akan bergerak ke superfisial, lalu akan berikatan pada membran dan organela kemudian berfusi sehingga keratinnya ini akan bewarna, granula yang berisi lipid juga akan dikeluarkan pada lapisan keratin.

Cells that are driven from progenitor cells and ready for maturation passes the entire epithelium to form the protective layer.

Sel yang didorong dari sel progenitor dan siap untuk pematangan melewati seluruh epitel membentuk lapisan pelindung.

In general maturation in the oral cavity follows two main patterns:• Keratinization• Nonkeratinization• Parakeratinization pada kulit terjadi hanya

pada kondisi inflamasi tapi di mulut bisa pas normal

Keratinization or cornification is the formation of a surface of keratin. pembentukan keratin

Such process is seen in the oral mucosa of the palate, gingiva and in some regions of the tongue dorsum.

A keratinized epithelium shows in histological sections a number of layers (strata)

Nonkeratinization occurs in regions with less mechanical influences to the OM, such as cheek, lips, underside of the tongue and the soft palate.

Nonkeratinized epithelium is usually thicker than keratinized epithelium.

No sudden changes in the cells above the st. spinosum occur in nonkeratinized epithelium

In so called parakeratinized mucosa, such as parts of the hard palate and the gingiva, in the surface layer the nuclei are shrunken and retained in many or all squames. Also keratohyaline granules are present in this layer. Masih ditemukan nukleus

Such phenomenon is a normal event in the oral epithelium, but not true for the epidermis, where parakeratinization is associated with diseases such as psoriasis.

• in the masticatory mucosa - large amounts of keratin are present >> so the outermost layer = keratinized layer

• BUT in the lining mucosa – no keratin is made – this layer is called the superficial layer

• presence of keratin prevents growth of microorganisms and physical damage

• covered in secretions from glands to provide some moisture• cells are flattened = squames• keratinized layers – cells do not contain nuclei• pattern of keratinization in these cells = orthokeratinization• a variation in keratinization is seen in the mucosa of parts of

the hard palate and much of the gingiva = parakeratinized mucosa

• only the cells in the surface stain for keratin and the nuclei are retained in many or all of the squames + fewer keratohyaline granules in the underlying granular layer (immature form of orthokeratinization)

• in the skin – parakeratinization is a disease state (e.g. psoriasis)

• – normal in oral mucosa• the keratinized mucosa of the oral cavity – 20 cell layers thick

-can be thicker than the palms and soles!!!!

keratinized layer/superficial layer = stratum corneum

In nonkeratinizing epithelia, the accumulation of lipids and of cytokeratins in the keratinocytes is less evident and the change in morphology is far less marked than in keratinizing epithelia. (pada nonkeratinisasi akumulasi lipid dan keratin kurang dan perubahan morfologi kurang sedangkan pada yang keratinisasi jelas)

The mature cells in the outer portion of nonkeratinized epithelia become large and flat and possess a cross-linked protein envelope, but they retain nuclei and other organelles, and the cytokeratins do not aggregate to form bundles of filaments, as seen in keratinizing epithelia. ( sel yang matur pada permukaan luar dari epitel nonkeratinisasi terlihat lebih besar dan pipih tapi masih mempertahankan nukleusnya)

keratinizing vs non keratinizing epithelia

Epithelial maturation in keratinized oral mucosa

Orthokeratinization of stratified squamous epithelium may occur at sites in the oral cavity where the mucosa is subjected to habitual mechanical stress - such as continuous trauma from chewing. Note the stratum corneum (A). No nuclei are visible in contrast with the parakeratinized variety. Lapisan epitel yang mengalami keratinisai juga disebut sebagai orthokeratinisasi. PadaTerjadi pada rongga mulut dimana mukosanya mendapat tekanan mekanis, misalnya pada gingiva, tidak ada nukleusnya lagi.

The mucosa covering the hard palate exhibits a distinct keratinized layer -High connective tissue papillae are associated with keratinized epithelium. -This form of keratinization in the oral cavity is referred to as orthokeratinized stratified squamous epithelium.

This is a section of labial mucosa. The epithelium (B) is non-keratinized stratified squamous. Examine the uppermost layer (*) carefully and note that these cells still exhibit nuclei. The loose connective tissue of the lamina propria that underlies the epithelium inserts up into this overlying layer in finger-like projections or papillae (A). -the non-keratinized epithelium is very thick

Parakeratinized epithelium of gingiva.Note the connective tissue papillae (A). The overlying epithelium is keratinizedThere is the absence of a distinctive stratum granulosum and the presence of nuclei (*) in the outermost layers (absent in a stratum corneum). Tapi piknotik

- dorsum of the adult tongue. - The majority of the tiny projections in this image are filiform papillae (A). - They are exposed to constant abrasive action during eating, talking, swallowing, etc. This results in their tips becoming protected by a layer of keratin. - A buildup of keratin can result in their elongation – has a hairy appearance = hairy tongue

This is the histological appearance of filiform papillae. Keratinization (A) occurs on the tips of these papillae. Each papilla has a core of connective tissue (B).

Histologic sections of three types of lingual papillae.

A, Several filiform papillae and a fungiform papilla from the anterior part of the tongue. The epithelium of the filiform papillae is keratinized; that of the fungiform papilla is keratinized thinly or nonkeratinized.

B, Section through the foliate papilla. The nonkeratinized epithelium covering the papilla contains numerous taste buds (arrowheads) situated laterally.

C, Histologic section of taste buds in the epithelium of circumvallate papillaA deep groove runs around the papilla, and the glands of Ebner empty into it.

Inset: Enlarged view of a simple taste bud with its barrel-like appearance and the apical pore (arrowhead).

The turnover time is the period of time is needed by a cell to divide and pass through the entire epithelium. Periode yang dibutuhkan sel untuk membelah dan mengalami maturasi sampe pada lapisan superfisial

The turnover time is 52 to 75 days in skin, 41 to 57 days in the gingiva and 25 days in the cheek.

Homeostasis dari epitel, ada keseimbangan antara sel basalis dengan sel yang mengelupas.

The concept of epithelial homeostasis implies that cell production in the deeper layers will be balanced by loss of cellsfrom the surface

Mitotic activity affected by a number of factors, such as time of day, stress, and inflammation. For example, the presence of a slight subepithelial inflammatory cell infiltrate stimulates mitosis, while severe inflammation causes a marked reduction in proliferative activity. Aktivitas mitosis dipengaruhi oleh beberapa faktor seprti waktu, hari, stres dan imflamasi. Inflamasi yang ringan menstimulasi mitosis, kalau berat mempengaruhi aktivitas proliferasi.

After cell division, each daughter cell either recycles in the progenitor population or enters the maturing compartment. The switch between proliferation and differentiation is modulated by the presence of factors, such as extracellular calcium, phorbol esters, retinoic acid, and vitamin D3 . Maturasi di pengaruhi oleh kalsium , phorbol ester, retinoid acid dan vitamin d3

Melanocytes – basal layer – menghasilkan melanosit-warna Merkel cells - basal layer- sel yang saraf

- is a sensory cell responding to touch Langerhans’ cells –fungsi imunologi, mampu untuk mengenali

material yang masuk dan memperkenalkan ke limfosit T

– they can move in and out of the epithelium

- They have an immunologic function, recognizing & processing antigenic material that enters the epithelium from the external environment and presenting it to helper T lymphocytes.

Inflammatory cells -- limfosit –T dan B (B—plasma--antibodi)

- mostly lymphocytes >>pmn (pada keadaan normal biasanya limfosit lebih sering dari pmn)

They do not participate in the process of maturation

Preparat oral epithelium menggambarkan melanocyte (panah) (Pewarnaan Masson’s Fontana)

A B

B. Preparat lapisan superficial oral epithelium B. Preparat lapisan superficial oral epithelium menggambarkan sel Langerhans cells (panah) menggambarkan sel Langerhans cells (panah) (ATPase)(ATPase)

keratinocytes produce interleukins (1, 6, 7, 8, 10, 11, and 12), colony-stimulating factors (GM, G, and M), and tumor necrosis factor-, all of which modulate the function of Langerhans’ cells.

In turn, Langerhans’ cells produce IL-1, which can activate T lymphocytes, which secrete IL-2, thus bringing about proliferation of T cells capable of responding to antigenic challenge.

IL-1 also increases the number of receptors to melanocyte-stimulating hormone in melanocytes and so can affect pigmentation.

The influence of keratinocytes extends to the adjacent connective tissue where cytokines produced in the epithelium can influence fibroblast growth and the formation of fibrils and matrix.