EPITHELIUM

PRESENTED BY:

DR. KALPAJYOTI BHATTACHARJEE

DEPT. OF ORAL PATHOLOGY AND MICROBIOLOGY

CONTENTS Definition

Development

Characteristics

Classification

Functions

Cell polarity

Membrane specialization of epithelia

Glands

Epithelial cell renewal

Structure of the oral epithelium

DEFINITION

Epithelium is an avascular tissue composed of cells

that cover the exterior body surfaces and line internal

closed cavities (including the vascular system) and

body tubes that communicate with the exterior (the

alimentary, respiratory, and genitourinary tracts).

Epithelium also forms the secretory portion

(parenchyma) of glands and their ducts. In addition,

specialized epithelial cells function as receptors for

the special senses (smell, taste, hearing, and vision).

DEVELOPMENT

EPITHELIUM IS DERIVED FROM 3 GEREM LAYERS

ECTODERM MESODERM ENDODERM

ALTHOUGH MOST OF THE EPITHELIA ARE DERIVED FROM ECTODERM AND ENDODEREM

ECTODERM: Oral and nasal mucosa, cornea, epidermis of the skin & glands of the skin & the mammary glands.

ENDODERM: The liver, the pancreas & the lining of the respiratory and GIT.

MESODERM: Uriniferous tubules of the kidney, the lining of the male and female reproductive systems, the endothelial lining of the circulatory system and the mesothelium of the body cavity.

CHARACTERISTICS

They are closely apposed and adhere to one another by

specialized cell junctions.

They exhibit functional and morphologic polarity through

a free surface or apical domain, a lateral domain, and a

basal domain.

Their basal surface is attached to an underlying

basement membrane.

EPITHELIAL CELLS that lack a free surface are

seen in:

interstitial cells of Leydig in the testis

the lutein cells of the ovary

the parenchyma of the adrenal gland

anterior lobe of the pituitary gland

Epithelioreticular cells of the thymus

certain types of injury, Infections and tumors

EPITHELIUM creates a selective barrier between the external environment and the underlying connective tissue seen in

Blood

lymph

CLASSIFICATION1) SIMPLE:• Squamous• cuboidal• columnar

2) PSEUDOSTRATIFIED

3) STRATIFIED• Squamous non keratinised• Squamous keratinised• Cuboidal• Columnar• transitional

SIMPLE- When it is one cell layer thick

STRATIFIED- When it has two or more cell layer.

SQUAMOUS- When the width of the cell is greater than its height.

CUBOIDAL- When the width, depth & height are approximately the same.

COLUMNAR- When the height of the cell approximately exceeds the width.

SIMPLE SQUAMOUS EPITHELIUM

Composed of flattened, irregularly shaped cells forming a continuous surface which may be reffered to as pavemented epithelium.

Term ‘squamous’ derives from the comparison of the cells to the scales of a fish.

Supported by an underlying delicate membrane.

Involved in passive transport of either gases or fluids.

PRESENT IN: Lining- pulmonary alveoli, loop of Henle, parietal

layer of Bawman capsule, inner and middle ear, blood and lymphatic vessels, pleural and peritoneal cavities.

FUNCTION:

Limiting membrane Fluid transport Gaseous exchange Lubrication Reducing friction Lining membrane

SIMPLE SQUAMOUS EPITHELIUM

SIMPLE CUBOIDAL EPITHELIUM

Intermediate form between simple squamous and simple columnar epithelium.

Nucleus is round and located in the centre of the cell.

Present in: Ducts of exocrine glands Surface of ovary Kidney tubules Thyroid follicles

Functions: Secretion Absorption Surface barrier

SIMPLE CUBOIDAL EPITHELIUM

SIMPLE COLUMNAR EPITHELIUM

Cells are taller and appear columnar in sections at right angles to the basement membrane.

Nuclei are elongated and may be located towards the base, the centre or occasionally the apex of the cytoplasm, this is known as polarity.

PRESENT IN: Small intestine & colon Stomach lining and gastric glands Gall bladder

FUNCTION: Transportation Absorption Secretion Protection

SIMPLE COLUMNAR CILIATED EPITHELIUM

Described as a special entity because of the presence of surface specialisation called cilia.

Each cilia consists of a finger like projection of the plasma membrane.

Not common in humans except in the female reproductive tract.

Simple columnar ciliated epithelium

GOBLET CELL These are modified columnar epithelial cells

which synthesize and secrete mucin. Scattered among the cells of many epithelial

linings particularly respiratory and GIT. Mucus content stain for glycoprotein using

PAS. The part of the cell where secretory vesicle

accumulates bulges and compresses the neighboring cells.

PSEUDOSTRATIFIED COLUMNAR EPITHELIUM

The term pseudostratified is derived from the appearance of this epithelium in section which conveys the erroneous impression that there is more than one layer of cells.

True simple epithelium since all the cells rest on the basement membrane.

Nuclei are disposed at different levels thus creating the illusion of cellular stratification.

Exhibit polarity with nuclei confined to the basal two-third of the epithelium, cilia are never present on stratified epithelium

PRESENT IN:Trachea & bronchial treeDuctus deferensAuditory tube and tympanic cavityNasal cavity & lacrimal sacMale urethraLarge excretory ducts

FUNCTION:SecretionAbsorptionLubricationTransportationProtection

STRATIFIED SQUAMOUS EPITHELIUM

It consists of a variable number of cells layer which exhibit transition from a cuboidal basal layer to a flattened surface.

Basal layer divide continuously.

Well adapted to withstand abrasion since loss of surface cells does not compromise the underlying tissue.

Nuclei become progressively condensed (pyknotic) and flattened, before ultimately disintegrating.

STRATIFIED SQUAMOUS EPITHELIUM

STRATIFIED SQUAMOUS NONKERATINISED EPITHELIUM

Flattened with nuclei.Moist superficial cells are living.

PRESENT IN:MouthEpiglottisEsophagusVocal foldsVagina

FUNCTION:ProtectionSecretion

STRATIFIED SQUAMOUS KERATINIZED EPITHELIUM

Flattened without nucleiDry, superficial cells are dead.Nuclei are lost.

PRESENT IN:Epidermis of skin.

FUNCTION:Protection.

STRATIFIED CUBOIDAL EPITHELIUM

Thin, stratified epithelium which usually consists of only two or three layers of cuboidal or low columnar cells.

Not involved in significant absorptive or secretory activity

PRESENT IN:Ducts of sweat glandsLarge ducts of exocrine glandsAnorectal junction

FUNCTION:AbsorptionSecretion

STRATIFIED COLUMNAR EPITHELIUM

PRESENT IN:Conjunctiva of eyeSome large excretory ductsPortions of male urethra

FUNCTION:SecretionAbsorptionProtection

TRANSITIONAL EPITHELIUM Form of stratified epithelium.

Highly specialized to accommodate a great degree of stretch.

So named because it has some features which are intermediate (transitional) between stratified cuboidal and stratified squamous epithelia.

In relaxed state (contracted) state, transitional epithelium appear to be about 4-5 layers thick. basal cells are roughly cuboidal , the intermediate cells are polygonal, and the surface cells are large and rounded and may contain 2 nuclei.

In the stretched state, it appears 2-3 cells thick (although the actual number of layers remains constant) and the intermediate and surface layers are extremely flattened.

PRESENT IN:UrethraUretersBladdersRenal calyces

FUNCTION:ProtectionDistensible

FUNCTIONS

1) Protection of underlying tissue of the body from abrasion and injury

2) Transcellular transport of molecules across epithelial layers

3) Secretion of mucus, hormones, enzymes and so forth from various glands.

4) Absorption of materials from a lumen

5) Control of movement of materials between body compartments via selective permeability of intracellular junctions between epithelial cells.

6) Detection of sensations via taste buds, retina of the eye and specialized hair cells in the ear.

CELL POLARITY

The free or apical domain is always directed towards the exterior surface or the lumen of an enclosed cavity or tube. It is rich in ion channel, carrier protein and hydrolytic enzymes as well as aquaporins, channel forming proteins that function in regulation of water balance.

Lateral domain communicates with adjacent cells & is characterized by specialized attachment areas.

The basal domain rests on the basal lamina

anchoring the cell to underlying connective tissue.

MEMBRANE SPECIALIZATION OF EPITHELIA

The intercellular, luminal and basal surface of epithelial cells exhibit a variety of specialization.

1) INTERCELLULAR SURFACE: The apposed surface of epithelial cells are lined

by several different types of membrane and cytoskeletal specialization. Cell junctions are:

a) Occluding or tight junctions: Located immediately behind the luminal surface

of simple columnar epithelium Intercellular spaces are oblitereted Transmembrane adhesive protein- occludin,

claudin, junctional adhesive molecule

Each tight junction forms a continuous circumferential band or zonules around the cell and are thus known as zonula occludens.

FUNCTIONS: Seal adjacent cells together Involved in cell signaling Defines apical and basolateral domain of

plasma membrane.

Tightness of the junction is related to the claudins present

b) Adhering junctions:

Tightly binds the constituent cells of the epithelium together and acts as an anchorage

Cytoskeleton of all the cells are effectively linked into a single functional unit

Apoptosis, loss of cell polarity, unregulated cell proliferation are absent.

Important in cellular signaling

Intercellular space- 20nm

CELL TO CELL ADHESIVE JUNCTION:

Transmembrane protein – cadherin Cytoplasmic adaptar protein- catenin

Zona adherens- e-cadherin A&B catenins, nectins actin filaments

Macula adherens- A desmosome  also known as macula adherens is a cell structure specialized for cell-to-cell adhesion.

Desmoglein & desmocollin Desmoplakin, Plakoglobin, Plakophollin Intermediate filaments

CELL TO CELL MATRIX JUNCTION:

Focal adhesion which anchor actin filaments of the cytoskeleton into the basement membrane

Integrin, A-actinin, vinculin, talin, actin filaments, remodelling of actin filaments.

Hemidesmosomes which anchor the intermediate filaments of the cytoskeleton into the basement membrane.

Hemidesmosomes are asymmetrical and are found in epithelial cells connecting the basal face of the cell to basal lamina. Similar in form to desmosomes when visualized by electron microscopy

Integrin, A6B4, BP230, Plectin, intermediate filaments links the cells to the basal lamina.

Hemidesmosomes

c) Gap junction:

Circular intercellular contacts areas containing hundreds of tiny pores which permit passage of small molecules between adjacent cells.

Intercellular space- 2-3 nm Transmembrane protein- connexin (form aqueous

channels) Function-:-

Creates a (nexus) adjacent cell conduct

between two adjacent cells for passage of small

ions and informational micromolecules.

2) LUMINAL SURFACE:

Luminal surface of epithelial cells may incorporate 3 main types of specialization:

a)cilia b)microvilli c)stereocilli

CILIA

Relatively long motile structure which are resolved by light microscopy

They are hairlike extensions of the apical plasma membrane containing an axoneme, the microtubule-based internal structure.

Cilia give a “crew-cut” appearance to the

epithelial surface basal bodies.

MOTILE CILIA

Active movement due to the presence of microtubule associated proteins; rapid forward movement with slow recovery stroke (half cone trajectory).

most commonly found on epithelia which function in transporting secretions .

present on sperm cells as flagella; provides a forward movement to the sperm cell.

Motile cilia are capable of moving fluid and

particles along epithelial surfaces eg. Tracheobronchial tree and oviduct.

PRIMARY CILIA

found in almost all cells in the body .

transmit signals from extracellular space into the cell.

No active movement; passively bend due to flow of fluid.

Function: chemosensors osmosensors mechanosensors.

NODAL CILIA

Structure similar to primary cilia except they have an ability for active transport, active rotational movement

Found in the embryo during gastrulation on the bilaminar disc near the area of primitive node.

Essential in developing left-right asymmetry of internal organs.

MICROVILLI

Microvilli are fingerlike cytoplasmic projections on the apical surface of most epithelial cells .

In intestinal absorptive cell this surface structure was originally called the striated border; in the kidney tubule cells, it is called the brush border.

Can not be individually resolved with the microscope

Internal structure contain a core of actin filament that are cross linked by several actin binding protein

Increase absorptive capacity

STREOCILIA

Stereocilia are unusually long, immotile microvilli.

Found only singly or in small number in odd sites such as the male reproductive tracts.

Contains ezrin and A-actinin.

Treadmilling effect- structure renewal process

STREOCILLIA

3) BASAL SURFACE

The interface between all epithelia and underlying supporting structures is marked by a noncellular structure known as the basement membrane.

It provides structural support for epithelia and constitute a selective barrier to the passage of material between epithelium and supporting tissue.

Hemidesmosomes provides a mean of anchorage of the cells via its cytoskeleton to the basement membrane and underlying supporting tissue

Consists of 3 zones: lamina lucida lamina densa lamina fibroreticularis or sublamina densa

LAMINA DENSA

The lamina densa is a component of the basement membrane zone between the epidermis and dermis of the skin, and is an electron-dense zone between the lamina lucida and dermis.

Synthesized by the basal cells of the epidermis

Electron dense matrix 50nm thick between the epithelium and the adjacent connective tissue

Exhibit a network of fine, 3-4nm filaments composed of laminins, a type iv collagen molecule (chicken-wire) and proteoglycans and glycoprotein.

LAMINA LUCIDA  The lamina lucida is a component of the

basement membrane which is found between the epithelium and underlying connective tissue.

Clear zone 40nm thick that attach the cells to the basal lamina

Contain- collagen type xvii, integrins, laminin v

Anchoring fibrils consists of collagen type vii attach basal lamina to connective tissue.

GLANDS

Typically glands are classified into:

1)Exocrine glands discharge their secretory product via a duct onto an epithelial surface. Cells of which are composed of highly specialized epithelial cells, the internal structure of the cells reflecting the nature of the secretory product and the mode of secretion.

Morphology: a)simple: single, unbranched duct. b)compound: branched duct

system.

2)Endocrine glands are ductless. Secrete their product into the connective tissue where they enter the blood stream to reach the target cells. The products of endocrine glands are called hormone.

In some epithelia, individual cells secrete a substance that does not reach the blood stream but rather affects other cells within the same epithelia. Such secretory activity is referred to as paracrine. The secretory material reaches the target cells by diffusion through the extracellular space or immediately subjacent connective tissue.

Cells of exocrine glands exhibit different mechanism of secretion:

Merocrine secretion- involves the process of exocytosis and is the most common form of secretion, protein are usually the major secretory product

Apocrine secretion- involves discharge of free, unbroken, membrane bound vesicles containing secretory product. This is an unusual mode of secretion and appears to lipid secretory products in the breasts and some sweat glands

Holocrine secretion- involves discharge of whole secretory cells with subsequent disintegration of the cells to release the secretory product. Occurs principally on the sebaceous glands.

EPITHELIAL CELL RENEWAL

The stratified squamous epithelium of skin is replaced in approximately 28 days.

Cells in the stratum basale undergo mitosis to provide for cell renewal.

As these cells differentiate they are pushed toward the surface by new cells in the basal layer.

Ultimately, the cells become keratinized and slough off.

Thus a steady state is maintained within the epithelium, with new cells normally replacing exfoliated cells at the same rate.

Cells arising by division in the basal layer may remain in the progenitor cell population or undergo a process of maturation as they move to surface.

EPITHELIAL METAPLASIA

Epithelial metaplasia is a reversible

conversion of one mature epithelial cell type

to another mature epithelial cell type.

Metaplasia is generally an adaptive response

to stress, chronic inflammation, or other

abnormal stimuli.

EPITHELIAL METAPLASIA

TUMOURS ARISING FROM EPITHELIA

A tumour can arise from any tissue if there is uncontrolled growth of cells.

A malignant tumour arising from an epithelia is a carcinoma.

If it arises from squamous epithelium it is a squamous cell carcinoma

If tumour arising from glandular epithelium it is called adenoma.

Diagnosis can be made by Immuno histochemical technique.

STRUCTURE OF THE ORAL EPITHELIUM

Stratified squamous variety.

May be keratinized (ortho or parakeratinized) or nonkeratinized depending on location.

Keratinized: gingiva and hard palate (masticatory mocosa). In many gingival epithelium is parakeratinized.

Non keratinized: cheeks, faucial and sublingual tissue.

Both keratinized and nonkeratinized contains 2 groups of cells- keratinocytes and nonkeratinocytes.

TURNOVER TIME OF THE EPITHELIUM

Turnover time- time taken for a cell to divide and pass through the entire epithelium.

E.g. – * skin - 52 to 75 days . * gut - 4 to 14 days. * gingiva - 41 to 57 days. * cheek - 25 days.

Nonkeratinised buccal epithelium turns over faster than keratinized gingival epithelium.

Keratinized epithelium: 1) stratum basale 2) stratum spinosum 3) stratum

granulosum 4) stratum corneum

STRATUM BASALE

Single layer of cuboidal cells

Made up of cells that synthesize DNA and undergo mitosis thus providing new cells

Basal cells and parabasal cells are referred to as stratum germinativum but only basal cells can divide.

Basal cells synthesize proteins

Hemidesmosomes are found in basal layer.

Lateral borders of the adjacent cells are closely apposed and connected by desmosomes.

The basal cells contain tonofilaments and are attached to the attachment plaque

Desmosomes consists of 2 principal proteins: transmembranous protein and proteins within the cells and related to attachment plaque.

STRATUM BASALE

STRATUM SPINOSUM

Irregular polyhedral cells larger than basal cells.

In light microscopy, it appears these are joined by “intercellular bridges”

Tonofilaments seems to course from cell to cell across the bridge.

Electron microscopy revels- intercellular bridges are desmosomes and tonofibrils are bundles of tonofilament.

Desmosome attachment plaques contain the polypeptides desmoplakin and plakoglobin.

Intercellular space contains glycoprotein, glycosaminoglycan and fibronectin.

Prickle cell layer- shrinks away from each other remaining in contact at the desmosomes.

Most active layer in protein synthesis.

STRATUM SPINOSUM

STRATUM GRANULOSUM

Flatter and wider cells larger than spinous cells

Contains basophilic keratohyalin granules

Nucleus show degeration and pyknosis.

Tonofilaments are more dense in quantity and are often seen associated with keratohyalin granules.

Cell surface are more regular and more closely attached to adjacent cell surface.

Lamellar granules: keratinosome or odland

body- membrane coating acts as permeability barrier.

Involucrin (keratolin)- protein present at the upper half.

Membrane coating granules are glycoprotein.

STRATUM GRANULOSUM

STRATUM CORNEUM

keratinized squamae which are larger and flatter

than granular cells.

Nuclei and organelles have disappeared.

Acidophilic and histologically amorphous layer.

Keratohyalin granules have disappeared.

Cells are composed of densely packed filaments

coated by basic protein of keratohyaline granules,

filaggrin.

STRATUM CORNEUM

Orthokeratinized epithelium: do not contain nuclei.

Parakeratinized epithelium: the stratum corneum retains pyknotic

nuclei.

Incomplete removal of the organelles from the cells of the granular layer occur so that the nuclei remain as shrunken pyknotic structure, and remnants of other organelles also may be present in the keratinized layer

ORTHOKERATINISED EPITHELIUM

PARAKERATINIZED EPITHELIUM

NONKERATINIZED EPITHELIUM

Layers Basal - (Stratum Basale) Intermediate - (Stratum Intermedium) Superficial - (Stratum Superficiale)

Basal cells are similar.

Cells of stratum intermedium are larger than

spinosum and are attached by desmosomes

and other junction.

More closely attached than spinous cells.

No Stratum Granulosum

No Stratum Corneum.

Stratum Superficiale – nucleated cells

Less number of tonofilaments

Lack keratohyaline granules.

Have higher rate of mitosis than keratinized epithelium.

Parakeratosis –physiologic normally keratinizing tissue becomes

parakeratinized.

Keratosis- Pathologic keratinization occurs in anormally

nonkeratinized tissue.

KERATINOCYTE

Epidermal/epithelial cells that synthesize keratin.

Characteristic intermediate filament protein is cytokeratin.

Show cell division, undergo maturation and finally desquamate

Increase in volume in each successive from basal to superficial.

NONKERATINOCYTES

Donot possess cytokeratin filament

Do not show mitotic activity undergo maturation and finally desquamate

Usually dendritic and appears unstained or clear in routine H&E stains

Identified by special stain or Imunohistochemical technique

Migrate to oral epithelium from neural crest or bone marrow.

MELANOCYTES

Present in basal layer.

Arise from neural crest ectoderm.

Staining reaction- dopa oxidase- tyrosinase,

silver stains.

Stained by : Mason-Fontana stain

Dendritic, no desmosomes and tonofilaments.

Premelanosomes and melanosomes are present.

Function- synthesis of melanin pigment granules

(melanosomes) and transfer to surrounding

keratinocytes.

LANGERHANS CELL

Present in suprabasal layer.

Arise from bone marrow.

Dendritic or clear cells with no desmosomes or

tonofilaments.

Characteristic langerhans granule- Birbeck

granules

Staining reactions- cell surface antigen markers

Stains by: gold chloride, ATPase &

immunofluorescent markers.

Function-

antigen trapping and processing.

LANGERHANS CELL

MERKEL CELLS

Present in basal layer.

Arise from division of epithelial cell.

Staining reaction- PAS positive.

Seen in masticatory mucosa but are absent in

lining mucosa

Non-dendritic with less desmosomes and

tonofilaments.

sensory and respond to touch.

Characteristic electron-dense vesicles and

associated nerve axon.

MERKEL CELLS

ULTRASTRUCTURE OF EPITHELIAL CELLS

Intracellular filaments- tonofilaments

Intracellular proteins- cytokeratins

Low mol wt keratin(40)- glandular & simple

Intermediate wt- stratified epithelia

Highest(67) – keratinized

stratified

Stratified oral epithelim - keratin 5 & 14

Keratinized epithelium - keratin 1, 6, 10, 16

Non-keratinized - keratin 4, 13, 19

REFERENCES

Michael H. Ross and Wojciech Pawlina; Histology A Text & Atlas; 6th edition; p.105-146

Kumar GS , Orban’s Oral Histology and Embryology, 12th Ed,2009,Elsevier,New Delhi, p.210-226.

Nanci A , Ten Cate’s Oral Histology Development structure and function, 7th Ed,2008,Mosby,New Delhi,p.320-336.

Singh.I,Histology of Human Histology Colour Atlas,5th Ed , Jaypee brothers , 2009,New Delhi, p.45-53.

Wheaters, functional histology, a text and colour atlas, 4th edition, page 80-96

BKB Berkovitz, oral anatomy, histology and embryology, 3rd edition, page 220-224

Leslic P. Gartner, colour textbook of histology, 3rd edition, page 85-109