Epithelium

epithelium seminar

1. EPITHELIUM PRESENTED BY: DR. KALPAJYOTI BHATTACHARJEE DEPT . OF ORAL PATHOLOGY AND MICROBIOLOGY

2. CONTENTS Definition Development Characteristics Classification Functions Cell polarity Membrane specialization of epithelia Glands Epithelial cell renewal Structure of the oral epithelium

3. 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).

4. DEVELOPMENT EPITHELIUM IS DERIVED FROM 3 GEREM LAYERS ECTODERM MESODERM ENDODERM ALTHOUGH MOST OF THE EPITHELIA ARE DERIVED FROM ECTODERM AND ENDODEREM

5. 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.

6. 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.

7. 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

8. EPITHELIUM creates a selective barrier between the external environment and the underlying connective tissue seen in Blood lymph

9. classification 1) SIMPLE: Squamous cuboidal columnar 2) PSEUDOSTRATIFIED 3) STRATIFIED Squamous non keratinised Squamous keratinised Cuboidal Columnar transitional

10. 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.

11. 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.

12. 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

13. SIMPLE SQUAMOUS EPITHELIUM

14. 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

15. Functions: Secretion Absorption Surface barrier

16. SIMPLE CUBOIDAL EPITHELIUM

17. 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

18. FUNCTION: Transportation Absorption Secretion Protection

19. 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.

20. Simple columnar ciliated epithelium

21. 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.

22. 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.

23. Exhibit polarity with nuclei confined to the basal two-third of the epithelium, cilia are never present on stratified epithelium PRESENT IN: Trachea & bronchial tree Ductus deferens Auditory tube and tympanic cavity Nasal cavity & lacrimal sac Male urethra Large excretory ducts

24. FUNCTION: Secretion Absorption Lubrication Transportation Protection

25. 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.

26. STRATIFIED SQUAMOUS EPITHELIUM

27. STRATIFIED SQUAMOUS NONKERATINISED EPITHELIUM Flattened with nuclei. Moist superficial cells are living. PRESENT IN: Mouth Epiglottis Esophagus Vocal folds Vagina FUNCTION: Protection Secretion

28. STRATIFIED SQUAMOUS KERATINIZED EPITHELIUM Flattened without nuclei Dry, superficial cells are dead. Nuclei are lost. PRESENT IN: Epidermis of skin. FUNCTION: Protection.

29. 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 glands Large ducts of exocrine glands Anorectal junction

30. FUNCTION: Absorption Secretion

31. STRATIFIED COLUMNAR EPITHELIUM PRESENT IN: Conjunctiva of eye Some large excretory ducts Portions of male urethra FUNCTION: Secretion Absorption Protection

32. 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.

33. 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: Urethra Ureters Bladders Renal calyces FUNCTION: Protection Distensible

34. 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.

35. 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.

36. 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.

37. 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

38. 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

39. 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

40. 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

41. 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.

42. Hemidesmosomes

43. 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.

44. 2) LUMINAL SURFACE: Luminal surface of epithelial cells may incorporate 3 main types of specialization: a)cilia b)microvilli c)stereocilli

45. 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.

46. 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.

47. 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.

48. 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.

49. 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

50. 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

51. STREOCILLIA

52. 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.

53. 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

54. 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.

55. 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.

56. 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 .

57. 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.

58. 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

59. 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.

60. 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.

61. 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.

62. 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.

63. EPITHELIAL METAPLASIA

64. 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.

65. 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.

66. 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.

67. Keratinized epithelium: 1) stratum basale 2) stratum spinosum 3) stratum granulosum 4) stratum corneum

68. 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

69. 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.

70. STRATUM BASALE

71. 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.

72. 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.

73. STRATUM SPINOSUM

74. 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.

75. 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.

76. STRATUM GRANULOSUM

77. 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.

78. STRATUM CORNEUM

79. 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

80. ORTHOKERATINISED EPITHELIUM

81. PARAKERATINIZED EPITHELIUM

82. NONKERATINIZED EPITHELIUM Layers Basal - (Stratum Basale) Intermediate - (Stratum Intermedium) Superficial - (Stratum Superficiale)

83. 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

84. No Stratum Corneum. Stratum Superficiale – nucleated cells Less number of tonofilaments Lack keratohyaline granules.

85. Have higher rate of mitosis than keratinized epithelium. Parakeratosis –physiologic normally keratinizing tissue becomes parakeratinized. Keratosis- Pathologic keratinization occurs in anormally nonkeratinized tissue.

86. 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.

87. 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.

88. 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.

89. 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.

90. LANGERHANS CELL

91. 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.

92. MERKEL CELLS

93. 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

94. REFERENCES Michael H. Ross and Wojciech Pawlina; Histology A Text & Atlas; 6 th edition; p.105-146 Kumar GS , Orban’s Oral Histology and Embryology, 12 th Ed,2009,Elsevier,New Delhi, p.210-226. Nanci A , Ten Cate’s Oral Histology Development structure and function, 7 th Ed,2008,Mosby,New Delhi,p.320-336.

95. Singh.I,Histology of Human Histology Colour Atlas,5 th Ed , Jaypee brothers , 2009,New Delhi, p.45-53. Wheaters, functional histology, a text and colour atlas, 4 th edition, page 80-96 BKB Berkovitz, oral anatomy, histology and embryology, 3 rd edition, page 220-224 Leslic P. Gartner, colour textbook of histology, 3 rd edition, page 85-109