keratinization process simplified

1. KERATINIZATION
Dr.Amy Mary Sebastian

2. LEARNING OBJECTIVES:
• KERATINIZATION-definition & characteristics.
• Epidermopoiesis
• Layers of epidermis & epidermal
• differentiation.
• Keratinization of hair
• Keratinization of nail
• Disorders Of Keratinization

3. DEFINITION
• KERATINIZATION
• Genetically programmed,
• Series of morphologic changes & metabolic
events .
• End point is a terminally differentiated
keratinocyte,
• contains keratin filaments, matrix proteins &
surface associated lipids.

4. KERATINIZATION-CHARACTERISTICS
• Involves:1.Nuclear changes
2.Cytoplasmic changes
• Increase in cell size & flattening
• Degradation of nucleus
• Synthesis of new cytoplasmic
organelles,sructural proteins & lipids.
• Dehydration

5. Keratinization-changes in keratinocytes

6. EPIDERMOPOIESIS:
1. Epithelial stem cells
2. Symmetrical & Asymmetrical
division model
3. Epidermal cell kinetics
4. Regulation of epidermopoiesis

7. EPITHELIAL STEM CELLS:
1.Epidermal SC
2.Sebocyte SC
3.Bulge SC

8. Division Models:
Symmetrical
• EPU=1 SC + 10 TAC
• TAC-Divides 4-5
times before
delamination.
• Lateral spindle
orientation.
Asymmetrical
• Preferential
partitioning of SC
into SC & Spinous
cell.
• Perpendicular
spindle orientation

9. Symmetrical & Asymmetrical Division:
TA-Transient Amplifying cell

10. Epidermal Cell Kinetics:
• Epidermal turnover time- 52-75 days.
• Depends upon: 1.Cell cycle time (50-457 hrs)
2.Growth fraction
Interphase
DNA synthesis
Pre Mitotic

11. Cell cycle measurement parameters:
• Mitotic Index: % of cells in mitosis at any point
• Labelling Index:
% of cells in S phase(DNA synthesis) at any
time.

12. Regulation of epidermopoiesis:
Activators:
• GFs –1.EGF & TGF ∝
(upregulates Amphiregulin)
2.Basic FGF
3.KGF (PDGF,IL 1β)
• Cytokines-IL 1 ,IL 6
• Integrins
• Calcium
• Retinoic acid
Inhibitors
• TGF 𝛽
• IFN 𝛼 , 𝐼𝐹𝑁 𝛾

13. Regulation of epidermopoiesis:

14. Layers of epidermis:
1. Stratum basale: 1 cell thick
• large dark nuclei with dense cytoplasm &
many ribosomes.
• Dense tonofilament bundles
2.Stratum spinosum: upper layers contain
odland bodies

15. 3.Stratum Granulosum:
• contains keratohyaline granules.
• Small lamellated granules called “Membrane
coating granules” or Odland bodies.
4.Stratum Lucidum:only in palmoplantar skin.
5.Stratum Corneum:
• Contains flattened cells without nuclei &
organelles- CORNEOCYTES.

16. Layers of epidermis

17. Epidermal Differentiation:
• Involves :
• Formation of keratin.
• Aggregation of keratin filaments.
• Formation of lipid barrier.
• Formation of a cornified envelope.
• Loss of integrin expression.
• Intercellular junctional interactions.

18. KERATIN
• The intermediate filament of keratinocytes.
• Structural integrity to the cell.
• 30% Protein of basal cells
• 85% Protein of corneocytes.
• Molecular wt 40-70 kDa.

19. Keratin:Types
• Type I Keratin
• Larger
• Basic
• Chr 12q
• K1-K8 in epidermis
• Hb1-Hb6 in hair follicle
• Type II Keratin
–Smaller
–Acidic
–Chr 17q
– K9-K20 in epidermis
–Ha1-Ha8 in hair
follicle

20. FORMATION OF KERATIN FILAMENTS

21. Simple epithelia K8/K18
Stratified squamous epithelia K5/K14
Basal keratinocytes of hair follicle K15
Supra basal –Differentiation specific K1/K10
Palmo plantar Epidermis K9
Hyperproliferative epithelia K6,K16,K17
Superficial interfollicular epidermis K2e
Cell specific keratins

22. Aggregation of keratin filaments:
• By FILAGGRIN (Histidine rich protein) in
Keratohyaline granules of S.granulosum.
PROFILAGGRIN
FILAGGRIN
UROCANIC ACID & PYRROLIDONE CARBOXYLIC ACID
(Filters UV & hydrates stratum corneum)

23. Formation of lipid barrier

24. Formation of cornified envelope:
• 20nm thick highly insoluble cell envelope deep to
plasma membrane.
• Contains large no. of glutamyl lysine isodipeptide
bonds formed by TRANSGLUTAMINASES.

25. Precursors of cornified envelope:
• INVOLUCRIN
• 3 membrane associated precursors:
Envoplakin
Periplakin
LORICRIN
• CYTOSOLIC PRECURSORS:
SPR-1(small proline rich protein 1)
Pancornulin

26. Formation of cornified envelope:
Intracellular calcium
Transglutaminase activation
Cross linking of plakins & involucrins
Highly insoluble cornified envelope

27. Formation of cornified envelope & Lipid barrier

28. Keratinization of hair
3 parts:
upper -Infundibulum
middle- Isthmus
lower-Inferior
segment

29. The Inferior section on C/S:

30. • In keratigenous zone the cells of hair follicle
begin to cornify.
• At this level Henle’s layer has a blue grey
colour because it has lost all trichohyaline
granules.
• Huxley’s layer maintain its trichohyaline
granules.

31. • ISTHMUS: Cornified inner sheath get
detached from outer sheath and isthmic
epithelium cornifies producing thin layer of
compactly arranged eosinophilic corneocytes.
• INFUNDIBULUM: Epithelium of hair follicle is
similar to epidermis.

32. KERATINISATION OF NAIL
• COMPONENTS OF NAIL
• Nail matrix
• Nail bed
• Nail plate
• Cuticle
• Lunula

33. • Nail matrix produces major part of nail plate
through onychokeratinisation
• Occures by accretion of tonofilaments without
formation of intervening keratohyaline
granules.

34. Nail differentiation
• Nail keratinocytes – interdigitations in electron
dense interfilamentous matrix.
• Keratins – K6b/K17
• Hair and nail keratins do not desquamate.

35. Disorders of keratinization
• Icthyotic disorders
Ichthyosis vulgaris – or absent fillagrin
Epidermolytic hyperkeratosis – mutation in gene
fork1/k10.
• Psoriatic disorders(Disorder of cell mediated immunity)
Hyperkeratosis – parakeratosis

36. Disorders of keratinization
• Palmoplantar keratodermas (Varied etiology)
Hyperkeratosis seen
• Epidermolytic- K1,K9 Diffuse-K1
• Non Epidermolytic
Focal-K16
• Follicular disorders
• Keratosis pilaris
• Pityriasis rubra pilaris
• Kyrle’s disease
• Hailey-Hailey disease , EBS- K5 & K14.

37. In a nutshell….
• Keratinization is a process in which
keratinocytes detach from the basal lamina
& move towards the skin surface.
• Epidermal stem cells by symmetrical/asymmetrical
division causes epidermopoiesis, + by EGF & TGF𝛼
- by TGF 𝛽, 𝐼𝐹𝑁𝑠
• Keratin is the intermediate filament – Types I & II
• Keratin filaments are aggregated by filaggrin in
keratohyaline granules.

38. In a nutshell….
• Lipids stored in odland bodies by
exocytosis forms the lipid barrier of skin.
• Corneocytes develop a highly insoluble
envelope by crosslinking Involucrins & Plakins
with the help of Transglutaminases.
• Hair & Nail are formed of hard keratin with high
sulphur content & they do not desquamate.

40. Thank
you!
“For not falling
asleep”