In Depth Description of the oral epithelium

1. 1

2. PRESENTED BY
DR SHRIKANT SONUNE
GUIDED BY
DR ASHOK PATIL
DR SHILPA KANDALGAONKAR
DR MAYUR CHOUDHARI
DR SUYOG TUPSAKHARE
DR MAHESH GABHANE

3. INTRODUCTION
Epithelium
Membrane
Cutaneous
membrane
Mucous
membranes
(mucosa)
Serous
membranes
(serosa)
Endothelium
Glands

4. Oral mucosa
 Epithelium- Stratified Squamous Epithelium
 Connective tissue
a lamina propria
submucosa.
 Oral mucosa is divided a/c to function into
1. Lining mucosa,
2. Masticatory mucosa,
3. Specialized mucosa

5. Specialized
mucosa
Lining mucosa
Masticatory
mucosa
Oral mucosa

6. Lining Mucosa
 Forms about 60% of surface area
 Nonkeratinized
 Distensible
 Relatively loosely bound .
 Found over mobile structures like
the lips, cheeks,
soft palate, alveolar mucosa,
vestibular fornix, and the floor of the mouth.

7. Masticatory Mucosa
 Form 25% of surface area
 Keratinized
 Rigid,
 Tough
 Tightly bound .
 Protective-covering component of
Gingiva
Hard palate
Alveolar ridge

8. Specialized Mucosa
 It is located on the dorsum of the tongue.
 Specialized mucosal structures the lingual papillae
and taste receptors.
 The heterogeneous pattern of keratin expression in the
tongue is complex
 In part is responsible for generating the papillary
architecture of the lingual epithelium.

10. Keratinized epithelium Nonkeratinized epithelium
 Superficial layer show no
nuclei(or pyknotic)
 Comparatively thin
 Increase in size comparatively
less
 Filaments aggregates in
bundle
 Superficial layer show viable
nuclei
 Comparatively thick
 Increase in size comparatively
more
 Filaments are dispersed

11. Keratinized epithelium Nonkeratinized epithelium
 Odland bodies are elongated
& contain a series of parallel
lamellae
 Effective barrier
 Keratohyalin granules
associated with
tonofilaments
 Odland bodies are circular
with amorphous core
 Forms comparatively less
effective barrier
 Keratohyalin granules are not
associated with
tonofilaments

12. Over view of oral epithelium
Architectural integrity Function
Cell to cell attachment Mechanical,
Basal lamina Chemical,
Keratin cytoskeleton Microbial barrier,
Signaling functions.
Major cell type Other cell type
Keratinocytes Langerhans cells,
Merkel cells,
Melanocytes,
Constant renewal
Replacement of damage cells

13. Structure of Basement
membrane
 A specialized extracellular molecular network,
constructed jointly by epithelial and connective tissue
cells.
 Pink-to-purple band approximately 0.5µm thick
 The basement membrane consists of
- Lamina densa
- Lamina lucida
- Lamina reticularis

14. Structure of Basement membrane

15. Basal lamina
 Basal lamina : Joins the epithelium to the underlying
connective tissue
 It consist of lamina densa & lamina lucida.
 The lamina densa a fibrillar layer
 The lamina rarae or lamina lucida electron-lucent
layer.
(Recent studies have shown that the lamina lucida is a
preparation artifact produced during tissue
dehydration. In reality, the basal lamina consists solely
of a lamina densa in direct juxtaposition to the cell
membrane.)

16.  Approximately 400 Å beneath the epithelial basal
layer
 Produced by the basal cells
 Light microscope
Structure less zone
 PAS stain positive

17. Basal lamina
 Lamina lucida : Laminin
 Lamina densa :
Type IV collagen +heparan sulphate
(chicken wire configuration )
 Permeable to fluids but acts as a barrier to particulate
matter

18. Lamina
Reticularis
 Characterized by a reticular network of collagens
(other than type IV).
 Merges with the underlying connective tissue.
 Anchoring fibrils (type VII collagen),
 Along with type I, type II

19. Function of Basement membrane
Foundation for epithelium
Line of demarcation
Promotes differentiation of epithelium
Promote peripheral nerve regeneration & growth
 Also tend to prevent metastases

20. Cytoskeleton of epithelium
Diameter Molecular wt
Smaller
Microfilaments
4-6nm 25kda
Intermediate
filaments
7-11nm 40-200kda
Large
microtubules
25nm 55kda

21. Intermediate Filaments
 Essential components of the cytoskeleton and
nucleoskeleton of all cells.
 Intermediate Filaments are products of the largest
family of cytoskeleton protein genes.
 In humans, at least 65 members of this multigene
family are presently known to encode these 10-12 nm
filaments.
 Epithelia have been characterized by containing
Specific types of proteins , that proteins known as
cytokeratins, which form the largest group of
Intermediate Filaments with about 50 genes.

22. Cytokeratins
 5classes of intermediate filaments have been
described:
i Acidic cytokeratins; Cytoplasmic
ii Basic cytokeratins; Intermediate Filaments
iii Vimentin, desmin
iv Neurofilaments Nuclear
v Nuclear lamins Intermediate Filaments

23. Cytokeratins
Acidic (type 1 cytokeratins ) Basic (Neutral, type II cytokeratins)
CK10, CK12,CK13, CK14, CK16,
CK17, CK18,CK19 and CK20
CK1, CK2, CK3, CK4, CK5, CK6,
CK7, CK8 and CK9

24. Cytokeratins
 Keratin proteins : Numbered in a sequence contrary to
their molecular weight
E.g. Lower molecular weight keratins (such as K19, )
 Always occurs in pairs of combination of type 1 &
type11
 Absence of pair susceptible to degeneration by
proteases
 Cytokeratins shows tissue & layer specificity

25. Function of Cytokeratins
Form a complex network which extends from the
surface of the nucleus to the cell membrane.
Organization of the cytoplasm and cellular
communication mechanisms.
Supporting the nucleus and providing tensile strength
to the cell.
Interact with desmosomes and hemidesmosomes.

26. Stratified Squamous epithelium
 Stratified Squamous keratinizing epithelium
(cutaneous type)
 Stratified Squamous Parakeratinizing epithelium
 Stratified Squamous Nonkeratinizing
epithelium(mucous type)

27.  Oral epithelium :stratified Squamous epithelium
 4 classical epithelial strata
1. Stratum basale
2. Stratum spinosum
3. Stratum granulosum
4. Stratum corneum

28.  The principal cell type : Keratinocyte
 Other cells : Non-keratinocytes / Clear cells
Langerhans cells
Merkel cells
Melanocytes
Inflammatory cells

29. Stratum basale
 Cells in the basal layer : single layer of Cuboidal to
columnar .
 Their nuclei are round to ovoid
 Situated away from basement membrane.
 All cell organelles are present.
 Filaments comprising k5 and k14 keratin chains
occupy roughly 25% of the cytoplasmic volume.

30. Basal cells synthesize and secrete
1.Type IV and type VII collagens,
2.Laminin,
3.Perlecan,
4.Parathyroid hormone- related peptide,
5.Cytokines(k5& k14)
As the cells differentiate, the nucleus-to-cytoplasmic
ratio decreases.

31. Cell renewal
Cell loss
Approximately 1 month
Keratinocyte reach the outer
epithelial surface, where it
becomes shed from the stratum
corneum
Epithelium maintains a
constant thickness.

32. Cell renewal
 Turn over time is follows-
1) For skin-52 to 75 days
2)For gut-4 to 14 days
3)For gingiva -41 to 57 days
4)Buccal mucosa -25 days
It depend on regional differences.
 Certain agents like cancer chemotherapeutic drugs &
inflammation affects epithelial turnover time.

33. Stratum Basale
Stem cells Serrated cells

34. Stem cells
 Nonserrated basal cells contain only a few cytoplasmic
organelles and appear to be the least differentiated cells
in the epidermis.
 High nucleus-to-cytoplasmic ratio,
 Expression of k19,
 Relative lack of keratin filament bundles,

35. Stem cells
 High levels of integrins.
 Contain melanin pigment as a result of their close
association with melanocytes.
 Expression of bcl-2 protein, an inhibitor of apoptosis.
 Administration of bromodeoxyuridine.

36. Proliferation

37. Serrated type cell
 Also known as transit amplifying cells.
 They have a serrated basal surface in contact with the
basement membrane.
 Numerous cytoplasmic processes (pedicles) that project
into the underlying connective tissue create the serrated
appearance.
 These basal cells appear specialized for anchoring the
epidermis to the connective tissue.
 The pedicles are rich in hemidesmosomes and have
well-developed filament bundles terminating at the
attachment plaques.

38.  Stratum spinosum
 Large, polyhedral cells
 Short cytoplasmic processes resembling spines
 Prickly appearance(spiny appearance ?)
 Cohesion : Desmosomes
Located between the
cytoplasmic processes
of adjacent cells

39. Stratum spinosum
 The stratum Spinosum forms the first layer of the differentiation
compartment.
 Most active in protein synthesis
 Here the expression of k1 and k10 keratins increases, while that of
k5 and k14 decreases.
 Cell-to-cell attachment increases dramatically
 Membrane-coating granules or lamellar granules are assembled in
the Golgi complex

40. Stratum spinosum
 They contain lamellar plates of fatty acids, cholesterol,
and sphingolipids.
 These lipid plates are released by exocytosis into the
intercellular spaces at the upper layers of the stratum
granulosum.
 This all changes indicate their biochemical
commitment to keratinization.

41.  Stratum Granulosum And Stratum Corneum
 Stratum granulosum
Keratohyalin granules
 Stratum granulosum
 Stratum corneum
 Very sudden keratinization
of the cytoplasm of the
keratinocyte &
conversion into horny squame
Abrupt transition

42. Stratum Granulosum
 Flatter & wider cells larger than spinous layer.
 Derives its name from its content of Keratohyalin
granules.
 The nuclei show signs of cell degeneration & pyknosis.
 m-RNA for filaggrin, the principal component of the
Keratohyalin granules and for loricrin and involucrin,
precursors of the cell envelope, increase in amounts in
the stratum granulosum.

43. Stratum Granulosum
 Membrane-coating granules continue to increase in
number and migrate to the peripheral cytoplasm close
to the plasma membrane in the outer layers of stratum
granulosum.
 Also known as keratinosomes, odland body , lamellar
granules
 Discharge content into intercellular space forming an
intercellular lamellar material.

44. Filled with keratin
Apparatus for protein synthesis & energy production
lost
 Complete keratinization Orthokeratinized
 Parakeratinized epithelium
 Nonkeratinized epithelium
Intermediate
stages of
keratinization
Stratum corneum

45.  Orthokeratinized epithelium
No nuclei in the stratum corneum
Well-defined stratum granulosum
Stratum corneum

46.  Parakeratinized epithelium
Stratum corneum retains pyknotic nuclei
Keratohyalin granules : Dispersed
Stratum corneum

47.  Nonkeratinized epithelium
Has neither granulosum nor corneum strata
Superficial cells : Viable nuclei
(shows stratum Basale, intermedium, superficiale)

48.  Proliferation and differentiation of the keratinocyte
Proliferation : Mitosis in the basal layer and less
frequently in the suprabasal layers
Differentiation : Keratinization

49.  Events of continuous differentiation
Cells lose the ability to multiply by mitotic division
Produce elevated amounts of protein, and
accumulate keratohyalin granules, keratin filaments
and macromolecular matrix in their cytoplasm
Lose the cytoplasmic organelles responsible for
protein synthesis and energy production

50. Eventually degenerate into a cornified layer due to the
process of intracellular keratinization, but without
loss of cell-cell attachment
Finally sloughed away from the epithelia surface and
into the oral cavity as the cell-cell attachment
mechanisms (that is, hemidesmosomes and gap
junctions) ultimately disintegrate

51.  Morphologic changes
Progressive flattening
 Prevalence of tonofilaments
 Intercellular junction
Keratohyaline granules
Disappearance of the nucleus
Str. basale
Str. spinosum
Str. granulosum

52.  Stratum corneum : K1 ,
 Other proteins
 Keratolinin
 Involucrin
 Filaggrin
Keratohyalin granules Filaggrin Matrix of
corneocyte

53.  Corneocytes
Bundles of keratin tonofilaments
Amorphous matrix of filaggrin
Resistant envelope under the cell membrane
 Interconnections
Desmosomes
Tight junctions (zonae occludens) : Less frequently

54.  Deeper strata
Numerous mitochondria
Succinic dehydrogenase
Nicotinamide-adenine dinucleotide
 Cytochrome oxidase
Other mitochondrial enzymes
Active tricarboxylic
cycle
Aerobic glycolysis

55.  Uppermost cells of the stratum spinosum
Keratinosomes or odland bodies
Modified lysosomes
Acid phosphatase : Enzyme involved in the
destruction of organelle membranes

56. NONKERATINOCYTES
 Do not possess cytokeratins filaments hence do not
have the ability to keratinize.
 Not arranged in layers
 Dendritic and appear unstained or clear
 They are identified by special stains or by
immunocytochemical methods.
 These cells migrate to the oral epithelium
1. From neural crest
2. From bone marrow.

57. Melanocytes
Langerhans
cells
Inflammatory
cell
Merkel's cells
Non-
keratinocyte
NONKERATINOCYTES

58.  Originate from neural crest cells
 Dendritic cells
 Premelanosomes or melanosomes
 Melanophages or Melanophores
Tyrosine
Dopa
Melanin
Tyrosinase
MELANOCYTES

59. MELANOCYTES
 Residing in the basal layer
 Establishes contact with about 30-40 keratinocytes
through their dendritic processes.
 Melanin produced by melanocytes Melanosome
 Melanocytes detected by
The dopa reaction
Silver-staining techniques.
Mosan Fontana stain
 Keratinocytes release mediators essential for normal
melanocytes function.

60.  Dendritic cells
 Modified monocytes
(hematopoietic origin)
 Mononuclear phagocyte system
 Macrophages with possible
antigenic properties
 Antigen-presenting cells
for lymphocytes
 G-specific granules (Birbeck's)
LANGERHANS CELLS

61.  It stains with
Gold chloride,
ATPase,
Immunofluorescent markers.
 Penetrate the epithelium from lamina propria.
 Has vimentin-type intermediate filaments.
 In the presence of antigenic challenge by bacterial
plaque Langenhans cells migrate into the gingiva.
 They also migrate into the epithelium in response to
chemotactic factors released by the keratinocytes to
the surface receptors of Langerhans cells.
 They shuttle between epithelium & regional lymph
nodes

62.  Originate from neural crest
 Present in Basal layer
 Harbour nerve endings
 Not dendritic
 Occasional desmosomes
 Tactile preceptors
 Stained by PAS stain.
MERKEL CELL

63.  Clinical normal areas of mucosa
 Nucleated cell layers
 Transient
 Lymphocytes : Most frequent
Associated with langerhans cells
 Polymorphonuclear leukocytes
 Mast cells
Inflammatory cells

64. Lateral Surface
Specializations
64

65. Cell junctions
 These are the sites where some kind of special contact
can be recognized between the cells
Can be classified in 3main types
1. Tight junction
2. Adhering junction
3. Gap junction (communicating junction)

66. Cell junctions
Another terms related to junctions are
1. Zonula a junction that extends around the perimeter
of cell like a belt.
2. Fascia if the junction occupies only the strip or patch
of cell surface.
3.Macula small & circular in outline.

67. types of Junctions in epithelia.
1. Zonula occludens
2. Zonula adherens
3. Macula communicans
1) Tight junction.
Zonula occludens (occluding junction, tight junction)
occurs on the lateral cell surfaces just beneath the
apical poles.
67

68. Structure of Tight junction
Formed by interactions of
special trans membrane
proteins (claudins,
occludin) in the plasma
membranes of adjacent
cells, these junctions form
a network that extends
completely around the cell
perimeter and represent
the closest contacts
between cells.
68

69. Functions.
Restrict Paracellular Flow
by restricting intercellular movement of materials.
Restrict Membrane Flow
They separate the apical and basolateral domains in cell
membranes, which insures that specific proteins will
remain in specific domains.
69

70. 2. Zonula adherens
It is also a band-like junction that extends around the
perimeter of cells; it serves in the attachment of
adjacent epithelial cells. Most numerous in oral
epithelium.
70

71. Macula communicans
 also known as
-communicating junction
-macula communicans,
-maculae communicantes
 This is a junctional area of between adjacent cells that
facilitates intercellular communication by allowing the
passage of small molecules and ions across the narrow
intercellular gap through a multitude of junctional
pores.
71

72. Structure of Macula
communicans
The junction consists of a
hexagonal lattice of
connexin protein subunits
called connexons, which
form intramembrane
hydrophilic channels
connecting the cytoplasm
of adjacent cells.
72

73. 73
Function.
 Permit intercellular signaling and electrical coupling by
allowing the regulated passage of ions and small
molecules between cells.
 Important cellular strategy for approaching the efficiency
of a syncytium.
{Pathologic hyperplasia & metaplasia usually
accompanied by reduction in gap junction
communication.}

74. Macula adherens (desmosome)
 Desmosomes are adhesive intercellular junctions,
which are found in tissues subjected to mechanical
strain.
 Widespread in epithelia,
 Particularly in stratified Squamous varieties.
 Intermediate (keratin) filament cytoskeletons across
cells.
 These junctions are “spot welds” between adjacent
cells,
 Which are formed by the juxtaposition and
attachment of two symmetrical disk-shaped structures
provided by each cell.
74

75. a. Structure: light microscopic.
At the Light Microscopic level, only observed in
Stratified Squamous Epithelium due to their high
density between cells.
 They appear as small punctate bodies,
 Hence onces they were considered as “cytoplasmic
bridges”
75

76. Structure: electron
microscopic
Their ultra structure
revealed that
desmosomes are
bipartite junctions,
which consist of
symmetrical, mirror-
image-like components
provided by each
adjacent cell.
76

77.  Intracellular components
Inside each cell, just beneath their lateral plasma
membranes, electron dense structures called attachment
plaques were found to connect the cell membrane on one
side with intermediate filaments of the keratin
cytoskeleton on the cytoplasmic side.
 Extracellular components
Between each cell in the middle of the intercellular space,
an intermediate dense midline was observed, which
appeared to be a region of attachment between adjacent
cells.
77

78. c. Structure: submicroscopic.
At the molecular level,
 specialized adhesive proteins.
major components cadherin superfamily of adhesion
molecules.
two major desmosomal cadherins have been described
and a schema for their nomenclature proposed
desmocollins and desmogleins.
Region-specific expression for various isoforms of these
proteins has also been shown to occur in Stratified
Squamous Epithelium.
78

79. Function.
 Most abundant in lining membranes subject to wear
and tear,
 Present in all epithelia,
 desmosomes are important cellular spot welds that
hold cells together by a calcium dependent adhesion
mechanism.
 They represent an important means of resistance to
lateral shearing forces between cells by coupling
external attachment of adjacent cells to internal
linkage of their keratin cytoskeletons across the
epithelium.
79

80. Structure of mucosa in different
regions
 Soft palate – thin (150micron), nonkeratinized
stratified Squamous epithelium ,taste buds present
 Ventral surface of tongue- thin nonkeratinized
stratified Squamous epithelium
 Floor of mouth-very thin (100micron),nonkeratinized
stratified Squamous epithelium

81. Structure of mucosa in different
regions
 Alveolar mucosa- thin nonkeratinized Squamous
epithelium.
 Labial & buccal mucosa -very thick
(500micron),nonkeratinized stratified Squamous
epithelium
 Lips vermilion zone -thin Orthokeratinized Squamous
epithelium
 Lips intermediate zone- thin Parakeratinized stratified
Squamous epithelium

82. Structure of mucosa in different
regions
 Gingiva -thick (250micron) Orthokeratinized
/Parakeratinized stratified Squamous epithelium,
showing stippled appearance.
 Hard palate- thick Orthokeratinized , stratified
Squamous epithelium thrown into transverse palatine
ridges (rugae).
 Dorsal surface of tongue- thick keratinized & non
keratinized stratified epithelium Squamous
epithelium forming 3 types of lingual papillae, some
bearing taste buds.

86. References
 Orel cells & tissue by P. R. Garant,
 Orbans oral histology & embryology
(11th edition ,12th edition)
 Oral histology 5th edi ten cate
 Histo notes by aw gustafson

87. 87