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GOOD MORNING….
ORAL EPITHELIUM
DR NAVEEN PARVATHAREDDY
I MDS, NARAYANA DENTAL COLLEGE
CONTENTS
• INTRODUCTION
• TYPES OF ORAL EPITHELIUM
• KERATINOCYTES
CYTOKERATINS IN ORAL EPITHELIUM
KERATIN ASSOCIATED PROTEINS
• NON-KERATINOCYTES
• EPITHELIAL PROLIFERATION
• EPITHELIAL MATURATION
• CELLULAR EVENTS IN CELL MATURATION
• BASEMENT MEMBRANE
• EPITHELIAL DISORDERS
• SUMMARY
• REFERENCES
INTRODUCTION
THE TISSUE THAT FORMS THE SURFACE OF THE ORAL MUCOSA
ACTS AS A BARRIER
IT IS OF STRATIFIED SQUAMOUS TYPE
MAINTAIN STRUCTURAL INTEGRITY
DERIVED FROM
TYPES OF ORAL EPITHELIUM
ORTHOKERATINISED PARAKERATINISED NON KERATINISED
GINGIVAL EPITHELIUM
• JUNCTIONAL EPITHELIUM
• SULCULAR EPITHELIM
KERATINOCYTES
KERATINOCYTES CONSISTS OF 2 FUNCTIONAL POPULATIONS
• PROGENITOR POPULATION – PERFORMING
EPITHELIAL PROLIFERATION
• MATURING POPULATION – PERFORMING EPITHELIAL
MATURATION
 Keratins (previously also called cytokeratins) are
filament forming proteins of epithelial cells and are
essential for normal tissue structure and function
 Forms the cytoskeleton of all the epithelial cells,
along with microfilaments & microtubules.
 Provide mechanical linkage & distribute force over
wide area
Based on distribution
Soft keratin
Hard keratin
Based on X-ray diffraction pattern
Alpha
Beta
Feather keratins
Amorphous keratins
Based on amino acid sequence and charge
o Type I: Acidic proteins
: Keratins 9-20
o Type II: Basic or neutral proteins
: Keratins 1-8
Based on molecular weight
o Low molecular weight keratins(40kDa)
o Intermediate molecular weight keratins
o High molecular weight keratins(67kDa)
 Known as intermediate filament associated proteins
 These include
Filaggrin
Trichohyalin
Desmosomal proteins
Proteins of cornified cell envelope
FILAGGRIN
• CATIONIC PROTEIN; AIDS IN
DENSE PACKING OF KERATIN
• SYNTHESIZED IN THE
GRANULAR CELL LAYER
• FACILITATES DISULFIDE BOND
FORMATION
• MARKER FOR KERATINIZED
TYPE OF EPITHELIUM
TRICHOHYALIN
• EXPRESSED IN THE KERATINIZING FILIFORM PAPILLA OF
TONGUE
• SINGLE STRANDED ALPHA-HELICAL ROD THAT BIND
KERATIN
• FUNCTION AS INTRACELLULAR CEMENT
• ALSO FUNCTIONS AS CROSS BRIDGING PROTEINS.
DESMOSOMAL PROTEINS
• LINKS EPITHELIAL CELLS TO EACH OTHER; ATTACHES KERATIN
CYTOSKELETON TO CELL SURFACE
• INTEGRAL PROTEINS: DESMOGLEIN & DESMOCOLLIN
• CYTOPLASMIC PLAQUE PROTEIN: DESMOPLAKIN & PLAKOGLOBIN
• PLAQUE ASSOCIATED PROTEINS: PLAKOPHILIN, ENVOPLAKIN &
PERIPLAKIN
PROTEINS OF CORNIFIED CELL ENVELOPE
• DEPOSITED ON THE INNER FACE OF PLASMA MEMBRANE OF
KERATINOCYTES.
• BARRIER FUNCTION OF STRATIFIED KERATINIZED EPITHELIA
• EXPRESSED IN
• MOST ABUNDANT CE PROTEINS
oLORICRIN
oINVOLUCRIN
oSMALL PROLINE RICH PROTEINS (SPR’S)
 They together makes up 10% of cell population in
the oral epithelium
 In light microscope –
 No tonofilaments
 No maturation
 Different non- keratinocytes in oral epithelium are
Melanocytes
Langerhans cells
Merkel cells
Inflammatory cells
Melanocytes
LM EM
Langerhans Cells
H & E EM
Merkel Cells
INFLAMMATORY CELLS
 Progenitor cells present in the basal layer
 Dividing cells tend to occur on clusters
 Progenitor compartment consists of 2 functional sub
population of cells
◦ Small stem cells-
◦ Large amplifying cells-
 Turnover time of the epithelium is the time it takes
for a cell to divide and pass through the entire
epithelium
 Turnover time
Skin – 52 – 75 days
Gut – 4 – 14 days
Gingiva – 41 – 57 days
Cheek – 25 days
 Proliferation is controlled by biologically active
substances called cytokines
MATURATION
Maturation follows 2 main patterns
Keratinization
Non– keratinization
Keratinization
Occurs in masticatory mucosa which is tough
& resistant to abrasion
Histologically , shows a number of distinct
layers or strata
Stratum basale
Otherwise
Deepest layer
Formed by
Basal cells show
Stratum spinosum
 Otherwise
 Situated
 Contacts only at points known as intercellular bridges or desmosomes
 Basal and prickle cell constitutes
 Stratum germinivatum
LAMELLAR BODIES, LAMELLAR GRANULES,
MEMBRANE COATING GRANULES OR
KERATINOSOMES.
THESE GRANULES ARE
• SMALL
• MEMBRANE BOUND
• SIZE – 250 NM
• CONTAIN GLYCOLIPID
• ORIGINATE FROM GOLGI SYSTEM
ODLAND BODIES
Stratum granulosm
Next to spinous layer
Consists of large flattened cells
Cells contain small granules that stain immensely with
hematoxylin
KERATOHYALIN GRANULES
• CHARACTERISTIC FEATURE
• UNDER LM,EM
• IRREGULAR IN SHAPE
• SIZE 0.5 – 1 MICROMETER
• SYNTHESIZED BY RIBOSOMES
• KERATOHYALIN GRANULES ASSOCIATED WITH
TONOFIBRILS ,
• FILAGGRIN, LORICRIN
Stratum corneaum
Surface layer
Composed of very flat cells
Eosinophilic, do not contain any nuclei
This pattern of maturation is called orthokeratinization
Some times in some mucosa, retain the shrunken nuclei
called as parakeratinisation
Non keratinization
◦ Usually the lining mucosa
◦ Basal & prickle layers resemble that of keratinized
except the prickle cells of non- keratinized epithelium
are slightly larger and intercellular bridges are less
conspisious
Above the prickle layer, divided into 2 zones
Stratum intermedium
Stratum superficiale
# No granular layer
# Superficial layer contain plump nucleus
# Not stain intensely with eosin
spinous cell layer (s. intermedium)
In prickle cell layer, increase in size is more than that of
keratinized epithelium
Tonofilaments remain dispersed
Contain membrane bound granules
They are circular in shape, with an amorphous coat
Stratum superficiale
The cells of the superficial layer,
Are more flattened
Contain dispersed tonofilaments and nuclei
Number of cell organelles are diminished
Not dehydrated
• CELL SIZE
• TONOFILAMENTS
• KERATINS
• GRANULAR LAMELLAE
• PERMEABILITY BARRIER
Keratinised epithelia Non keratinized epithelia
 Depends on the
Thickness of the epithelium
Pattern of maturation
Thinnest epithelium allow better penetration
Permeability barrier is due to the lipids derived
from the membrane coating granules
BASEMENT MEMBRANE
• FORMED BY
• LM – AMORPHOUS, DENSE LAYER OF VARIABLE THICKNESS
• PAS STAIN - WELL DEFINED MAGENTA LAYER
• IN ELECTRON MICROSCOPE BM CONSISTS OF 3 LAYER
• LAMINA LUCIDA
• LAMINA DENSA
• LAMINA FIBRO-RETICULARIS
BASEMENT MEMBRANE
• MAIN CONSTITUENTS OF BM ARE
• THE GLYCOSAMINOGLYCAN, HEPARIN SULPHATE
• FIBROUS PROTEIN –COLLAGEN TYPE-IV , VII
• STRUCTURAL GLYCOPROTEINS – FIBRONECTIN , LAMININ &
ENACTIN
Functional role
 Compartmentalize tissues
 Anchor cell sheets
 Play major role in control of cell migration
 Act as an stimulus
 Serve as a barrier
 As epithelium devoid of blood vessels
 Fenestrations in BM
EPITHELIAL DISORDERS:
Epithelial atrophy Epithelial hyperplasia
HYPERKERATOSIS ULCERATED EPITHELIUM
ACANTHOLYSISACANTHOSIS
ORAL EPITHELIUM
• SERRATED AND NON-SERRATED BASAL CELLS
• CYTOKERATINS EXPRESSION
• SPECIAL STAINS FOR NON-KERATINOCYTES
SERRATED HEAVILY PACKED WITH TONOFILAMENTS WHICH
ARE ADAPTATIONS FOR ATTATCHMENT
NON-SERRATED - SLOWLY DIVIDING CELLS WHICH SERVE TO
PROTECT GENETIC INFORMATION OF TISSUE
• PERIMETER OF BOTH NUCLEUS & CYTOPLASM
• CYTOPLASM IS PRIMITIVE & CONTAIN
Cytokeratin expression in normal oral
mucosa:
Basal cells
• Keratinised sites : k5 & k14
• Non-keratinised sites : k19
Supra-basal cells
• Keratinised sites : k1 & k10
• Non-keratinised sites : k4 & k13
CYTOKERATINS EXPRESSION IN EPITHELIAL
TUMOR CELLS:
• best IHC marker for Merkel-cell
carcinomas
Ck 20
• markers for poorly differentiated
squamous cell carcinoma
Ck 13
• a marker for odontogenic epithelial
origin
Ck 14 & 19
Keratins can be used as differentiation markers in
normal oral epithelia:
• markers for simple epithelial differentiation
K8/18
• markers for keratinized epithelium
K1/10
• markers for non-keratinized epithelium.
K4/13
• considered as hyperproliferative markers
• expressed in sites of high epidermal keratinocyte turnover and in pathological
hyperproliferative conditions affecting the skin
K6/16
• MELANOCYTES-
• LANGERHANS CELLS-
• MERKEL CELLS-
• LYMPHOCYTES-
 Ten Cates Oral Histology – Antonio Nanci –
8th edition
 Anatomy, histology & embryology –
Berkovitz – 3rd edition
 Atlas of histology – Difiore’s – 9th edition
 Text book of basic histology – Wheater’s
 Text book of human histology – Inderbir
Singh – 5th edition
 Ham’s histology -9th edition
 Internet sources
Oral epithelium , dr naveen reddy

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Oral epithelium , dr naveen reddy

  • 2. ORAL EPITHELIUM DR NAVEEN PARVATHAREDDY I MDS, NARAYANA DENTAL COLLEGE
  • 3. CONTENTS • INTRODUCTION • TYPES OF ORAL EPITHELIUM • KERATINOCYTES CYTOKERATINS IN ORAL EPITHELIUM KERATIN ASSOCIATED PROTEINS • NON-KERATINOCYTES • EPITHELIAL PROLIFERATION • EPITHELIAL MATURATION • CELLULAR EVENTS IN CELL MATURATION • BASEMENT MEMBRANE • EPITHELIAL DISORDERS • SUMMARY • REFERENCES
  • 4. INTRODUCTION THE TISSUE THAT FORMS THE SURFACE OF THE ORAL MUCOSA ACTS AS A BARRIER IT IS OF STRATIFIED SQUAMOUS TYPE MAINTAIN STRUCTURAL INTEGRITY DERIVED FROM
  • 5. TYPES OF ORAL EPITHELIUM ORTHOKERATINISED PARAKERATINISED NON KERATINISED
  • 6. GINGIVAL EPITHELIUM • JUNCTIONAL EPITHELIUM • SULCULAR EPITHELIM
  • 7. KERATINOCYTES KERATINOCYTES CONSISTS OF 2 FUNCTIONAL POPULATIONS • PROGENITOR POPULATION – PERFORMING EPITHELIAL PROLIFERATION • MATURING POPULATION – PERFORMING EPITHELIAL MATURATION
  • 8.  Keratins (previously also called cytokeratins) are filament forming proteins of epithelial cells and are essential for normal tissue structure and function  Forms the cytoskeleton of all the epithelial cells, along with microfilaments & microtubules.  Provide mechanical linkage & distribute force over wide area
  • 9. Based on distribution Soft keratin Hard keratin Based on X-ray diffraction pattern Alpha Beta Feather keratins Amorphous keratins
  • 10. Based on amino acid sequence and charge o Type I: Acidic proteins : Keratins 9-20 o Type II: Basic or neutral proteins : Keratins 1-8 Based on molecular weight o Low molecular weight keratins(40kDa) o Intermediate molecular weight keratins o High molecular weight keratins(67kDa)
  • 11.  Known as intermediate filament associated proteins  These include Filaggrin Trichohyalin Desmosomal proteins Proteins of cornified cell envelope
  • 12. FILAGGRIN • CATIONIC PROTEIN; AIDS IN DENSE PACKING OF KERATIN • SYNTHESIZED IN THE GRANULAR CELL LAYER • FACILITATES DISULFIDE BOND FORMATION • MARKER FOR KERATINIZED TYPE OF EPITHELIUM
  • 13. TRICHOHYALIN • EXPRESSED IN THE KERATINIZING FILIFORM PAPILLA OF TONGUE • SINGLE STRANDED ALPHA-HELICAL ROD THAT BIND KERATIN • FUNCTION AS INTRACELLULAR CEMENT • ALSO FUNCTIONS AS CROSS BRIDGING PROTEINS.
  • 14. DESMOSOMAL PROTEINS • LINKS EPITHELIAL CELLS TO EACH OTHER; ATTACHES KERATIN CYTOSKELETON TO CELL SURFACE • INTEGRAL PROTEINS: DESMOGLEIN & DESMOCOLLIN • CYTOPLASMIC PLAQUE PROTEIN: DESMOPLAKIN & PLAKOGLOBIN • PLAQUE ASSOCIATED PROTEINS: PLAKOPHILIN, ENVOPLAKIN & PERIPLAKIN
  • 15. PROTEINS OF CORNIFIED CELL ENVELOPE • DEPOSITED ON THE INNER FACE OF PLASMA MEMBRANE OF KERATINOCYTES. • BARRIER FUNCTION OF STRATIFIED KERATINIZED EPITHELIA • EXPRESSED IN • MOST ABUNDANT CE PROTEINS oLORICRIN oINVOLUCRIN oSMALL PROLINE RICH PROTEINS (SPR’S)
  • 16.  They together makes up 10% of cell population in the oral epithelium  In light microscope –  No tonofilaments  No maturation
  • 17.  Different non- keratinocytes in oral epithelium are Melanocytes Langerhans cells Merkel cells Inflammatory cells
  • 22.  Progenitor cells present in the basal layer  Dividing cells tend to occur on clusters  Progenitor compartment consists of 2 functional sub population of cells ◦ Small stem cells- ◦ Large amplifying cells-
  • 23.
  • 24.
  • 25.  Turnover time of the epithelium is the time it takes for a cell to divide and pass through the entire epithelium  Turnover time Skin – 52 – 75 days Gut – 4 – 14 days Gingiva – 41 – 57 days Cheek – 25 days
  • 26.  Proliferation is controlled by biologically active substances called cytokines
  • 27. MATURATION Maturation follows 2 main patterns Keratinization Non– keratinization
  • 28. Keratinization Occurs in masticatory mucosa which is tough & resistant to abrasion Histologically , shows a number of distinct layers or strata
  • 29.
  • 31. Stratum spinosum  Otherwise  Situated  Contacts only at points known as intercellular bridges or desmosomes  Basal and prickle cell constitutes  Stratum germinivatum
  • 32. LAMELLAR BODIES, LAMELLAR GRANULES, MEMBRANE COATING GRANULES OR KERATINOSOMES. THESE GRANULES ARE • SMALL • MEMBRANE BOUND • SIZE – 250 NM • CONTAIN GLYCOLIPID • ORIGINATE FROM GOLGI SYSTEM ODLAND BODIES
  • 33. Stratum granulosm Next to spinous layer Consists of large flattened cells Cells contain small granules that stain immensely with hematoxylin
  • 34. KERATOHYALIN GRANULES • CHARACTERISTIC FEATURE • UNDER LM,EM • IRREGULAR IN SHAPE • SIZE 0.5 – 1 MICROMETER • SYNTHESIZED BY RIBOSOMES • KERATOHYALIN GRANULES ASSOCIATED WITH TONOFIBRILS , • FILAGGRIN, LORICRIN
  • 35. Stratum corneaum Surface layer Composed of very flat cells Eosinophilic, do not contain any nuclei This pattern of maturation is called orthokeratinization Some times in some mucosa, retain the shrunken nuclei called as parakeratinisation
  • 36. Non keratinization ◦ Usually the lining mucosa ◦ Basal & prickle layers resemble that of keratinized except the prickle cells of non- keratinized epithelium are slightly larger and intercellular bridges are less conspisious
  • 37. Above the prickle layer, divided into 2 zones Stratum intermedium Stratum superficiale # No granular layer # Superficial layer contain plump nucleus # Not stain intensely with eosin
  • 38. spinous cell layer (s. intermedium) In prickle cell layer, increase in size is more than that of keratinized epithelium Tonofilaments remain dispersed Contain membrane bound granules They are circular in shape, with an amorphous coat
  • 39. Stratum superficiale The cells of the superficial layer, Are more flattened Contain dispersed tonofilaments and nuclei Number of cell organelles are diminished Not dehydrated
  • 40. • CELL SIZE • TONOFILAMENTS • KERATINS • GRANULAR LAMELLAE • PERMEABILITY BARRIER Keratinised epithelia Non keratinized epithelia
  • 41.  Depends on the Thickness of the epithelium Pattern of maturation Thinnest epithelium allow better penetration Permeability barrier is due to the lipids derived from the membrane coating granules
  • 43. • FORMED BY • LM – AMORPHOUS, DENSE LAYER OF VARIABLE THICKNESS • PAS STAIN - WELL DEFINED MAGENTA LAYER • IN ELECTRON MICROSCOPE BM CONSISTS OF 3 LAYER • LAMINA LUCIDA • LAMINA DENSA • LAMINA FIBRO-RETICULARIS BASEMENT MEMBRANE
  • 44. • MAIN CONSTITUENTS OF BM ARE • THE GLYCOSAMINOGLYCAN, HEPARIN SULPHATE • FIBROUS PROTEIN –COLLAGEN TYPE-IV , VII • STRUCTURAL GLYCOPROTEINS – FIBRONECTIN , LAMININ & ENACTIN
  • 45. Functional role  Compartmentalize tissues  Anchor cell sheets  Play major role in control of cell migration  Act as an stimulus  Serve as a barrier  As epithelium devoid of blood vessels  Fenestrations in BM
  • 47.
  • 50.
  • 51. ORAL EPITHELIUM • SERRATED AND NON-SERRATED BASAL CELLS • CYTOKERATINS EXPRESSION • SPECIAL STAINS FOR NON-KERATINOCYTES
  • 52.
  • 53. SERRATED HEAVILY PACKED WITH TONOFILAMENTS WHICH ARE ADAPTATIONS FOR ATTATCHMENT NON-SERRATED - SLOWLY DIVIDING CELLS WHICH SERVE TO PROTECT GENETIC INFORMATION OF TISSUE • PERIMETER OF BOTH NUCLEUS & CYTOPLASM • CYTOPLASM IS PRIMITIVE & CONTAIN
  • 54. Cytokeratin expression in normal oral mucosa: Basal cells • Keratinised sites : k5 & k14 • Non-keratinised sites : k19 Supra-basal cells • Keratinised sites : k1 & k10 • Non-keratinised sites : k4 & k13
  • 55. CYTOKERATINS EXPRESSION IN EPITHELIAL TUMOR CELLS: • best IHC marker for Merkel-cell carcinomas Ck 20 • markers for poorly differentiated squamous cell carcinoma Ck 13 • a marker for odontogenic epithelial origin Ck 14 & 19
  • 56. Keratins can be used as differentiation markers in normal oral epithelia: • markers for simple epithelial differentiation K8/18 • markers for keratinized epithelium K1/10 • markers for non-keratinized epithelium. K4/13 • considered as hyperproliferative markers • expressed in sites of high epidermal keratinocyte turnover and in pathological hyperproliferative conditions affecting the skin K6/16
  • 57. • MELANOCYTES- • LANGERHANS CELLS- • MERKEL CELLS- • LYMPHOCYTES-
  • 58.  Ten Cates Oral Histology – Antonio Nanci – 8th edition  Anatomy, histology & embryology – Berkovitz – 3rd edition  Atlas of histology – Difiore’s – 9th edition  Text book of basic histology – Wheater’s  Text book of human histology – Inderbir Singh – 5th edition  Ham’s histology -9th edition  Internet sources