Structure of skin

Structure of skin
By Dr. Jikisha Jain
1st year resident (M.D. DVL)

1. Structure of skin By: Dr.Jikisha Jain

2. Skin Skin is the largest organ in the body. In a 70kg individual, the skin weighs over 5 kgs and covers a surface area approaching 2 square meter. Human skin is of two types:- Non hairy (glabrous)skin : as seen on palms and soles. Hair bearing skin

3. Human Skin Consists Of: Epidermis Dermis Hypodermis(subcutaneous fat )

4. Contents Of Epidermis And Dermis Cells Other structures Epidermis Keratinocytes,melanocytes,langerhans cells and merkel cells Hair follicles,apocrine glands and sweat glands which are derived from epidermis and extend to dermis Dermis Fibroblasts,mast cells,histiocytes,macrophages and lymphocytes Matrix of polysaccharides and protein

5. Epidermis It is stratified squamous epithelium which is terminally differentiated. Thickness:0.05-0.1mm. Keratinocytes constitute more than 95% of epidermal cells. The “ brick like “ shape of keratinocyte is provided by cytoskeleton made of keratin intermediate filaments. As epidermis differentiates, cells gets flattened. This process involves the filament aggregating protein called filaggrin . Keratin and filaggrin comprises 90% of mass of epidermis.

6. Epidermis On morphological grounds, the epidermis can be divided into four distinct layers: Stratum basale or stratum germinativum Stratum spinosum Stratum granulosum Stratum corneum

7. Malpighian layer includes both the basal and spinous cells.

8. Stratum Basale Continuous layer ,generally one cell thick but can be 2 -3 cell layer thick in glabrous skin and hyperproliferative skin. Basal cells are small and cuboidal with large dark staining nuclei and dense cytoplasm. It contains ribosomes , tonofilaments and melanosome s transferred from melanocytes by phagocytosis. It contains three types of cells: stem cells ,transient amplifying cells and post mitotic cells.

9. Stratum Spinosum Aka prickle cell layer . Contains 8-10 layers of cells. Cells are polyhedral with a round nucleus. The cells in upper spinous layer are more larger and flattened and contains “ lamellar granules ”. They are named spinous for the spine like appearance which corresponds to abundant desmosomes histologically.

10. Stratum Granulosum It is 2 -5 cells thick . Contains intracellular granules of keratohyalin. The cytoplasm of upper spinous layer and granular cell layer contains lamellated granules known as membrane coating granules or odland bodies . They discharge their lipid component into intercellular space playing an important role in barrier function and intercellular cohesion.

11. Stratum Corneum Outermost skin layer . Consist of 20-25 layers of cornified cells called as corneocytes which are largest cells of epidermis. They are flattened with no nuclei and cytoplasmic organelles. The corneocyte has a highly insoluble, cornified envelope within the plasma membrane formed by soluble protein precursor called as involucrin .

12. Stratum Lucidum An electron-lucent layer present in palms and soles between stratum granulosum and stratum corneum with nucleated transitional cells.

13. Epidermal cells Keratinocytes Ectodermal in origin. They contain keratin intermedite filaments or tonofilaments. The keratins are separated into two gene families : Type 1 (basic) Type 2(acidic)

14. Cells Keratin expression Simple epithelia K8/K18 Stratified squamous epithelium and basal layer K5/K14 Spinous layer K1/K10 Basal keratinocytes in bulge of hair follicle K15 Palmoplantar epidermis K9 Superficial interfollicular epidermis K2 Merkel cells K8,k18,k19,k20 K20 (specific)

15. Structural organization of keratin filament network inside a keratinocyte

16. Merkel Cells Slow adapting , type 1 mechanoreceptors . They are found in both in hairy skin and glabrous skin of digits ,lips ,region of oral cavity and outer root sheath of hair follicle. applied: in merkel cell carcinoma ,neuroendocrine carcinoma.

17. Merkel cell Spherical granules

18. Langerhans Cells Dendritic cells They are dopa negative and ATPase positive. Derived from bone marrow.

19. Distributed in basal,spinous and granular cell layers Cells are pale staining and have convoluted nuclei and clear cytoplasm, well developed endoplasmic reticulum and lysosomes. They have distinctive rod or racquet shaped granules called as birbeck granules . Function: antigen presentation,stimulatiom of t-cell response and phagocytosis. IHC markers: CD1a,S100.

20. Applied : cells are implicated in pathogenecity of allergic contact dermatitis,cutaneous leishmaniasis and HIV infection. In psoriasis ,sarcoidosis and contact dermatitis ,their number is reduced.

21. Dendritic appearance of langerhans cells

22. Convoluted lobes of nucleus in langerhans cells Racquet shaped granules

23. Melanocytes They are dendritic cells derived from neural crest that are involved in pigment synthesis. Melanocytes are in contact with keratinocytes through their processes but do not form junctions with them at any level. One melanocyte is in contact with 36 basal and suprabasal keratinocyte forming an epidermal melanin unit.

24. There is no difference in the density of melanocytes in different races. The racial differences are due to the distribution and size of melanosomes with keratinocytes.

25. Melanosomes Melanin is produced in melanosomes (pigment granules or organelles) within melanocytes. The major hormone controlling melanin synthesis is alpha-MSH (MELANOCYTE STIMULATING HORMONE) from pituitary gland. Two types of melanin present : Eumelanin (brown/ black) Pheomelanin (red/yellow)

26. Applied: in vitiligo ,melanocytes are destroyed. In albinism ,number of melanocytes are normal but they are unable to synthesize fully pigmented melanosomes . Freckles result from a localized increase in production of pigment by normal number of melanocytes. Nevi are benign proliferations of melanocytes and Melanomas are malignant counterpart .

27. Desmosomes major adhesion complex in epidermis. Anchor keratin filaments to the cell membrane. Bridge the adjacent keratinocytes.

28. Desmosomes have a characteristic ultra structure with cell membranes of two adjacent cells forming a symmetrical junction with a 30nm intercellular space containing a dense line. core has calcium binding glycoproteins called desmogleins and desmocollins .

29. There are three epidermis- specific desmogleins (Dsg 1-3) and desmocollins (Dsc 1-3).. Upper dermis expresses Dsg1 and Dsc 1 more. basal keratinocytes expresses Dsg 3 and Dsc 3 more. The intercellular parts 0f Dsg and Dsc are attached to keratin via desmoplakin ,plakoglobin and plakophilin.

30. Adherens junctions Electron dense transmembrane structures that associate with actin skeleton. Their main component is calcium dependent E-cadherin. The main linkage to actin cytoskeleton is via alpha –catenin.

31. Gap junctions Comprise a cluster of intercellular connections known as connexons. They allow transfer of molecules and ions (<1000 Da) between two cells.

32. Tight junctions Major regulators of permeability of epithelia. Composed of transmembrane and intracellular molecules that includes:- occludin junction adhesion molecules(JAM) claudins

33. Dermis It makes the bulk of skin. Unlike epidermis , it is highly acellular and consist of extracellular matrix of connective tissue . Thickness varies from 0.5mm to 5mm . There are four major components: Collagen fibres : provide tensile strength. Elastic structures : :provide elasticity and resilience . Glycoproteins such as fibrillins,fibulins and integrins : organizers of matrix Proteoglycans /glycosaminoglycans (GAGs): provide hydration.

34. Organization Of Dermis Dermis is organized into : papillary dermis reticular dermis A horizontal plane of vessels marks the boundary between them. The papillary dermis and periadnexal dermis are together known as adventitial dermis .

35. Papillary Dermis It is the superficial and thin part of the dermis that interdigitates with the ridges . Characterized by small bundles of collagen fibres and oxytalan fibres. Mature elastic fibres usually not found. high density of fibroblastic activity and a high metabolic rate .

36. Reticular Dermis It constitutes the lower part of the dermis and merges with the subcutaneous fat. Composed of large diameter collagen fibrils. Mature elastic fibres form a superstructure around the collagen fibre bundles.

37. Connective Tissue Matrix The main fibrous connective tissue of dermis is made of collagen and elastin fibres. collagen

38. Connective Tissue Matrix The main fibrous connective tissue s of the dermis are collagen and elastic connective tissues. Type of collagen Function Type I Larger in diameter forming large and coarse bundles present in reticular dermis. Type III Fibrils are smaller and form small and fine network mainly in papillary dermis and around blood vessels and adnexa. Type IV Limited to basal lamina. Type V Localized in papillary dermis. Type VI Abundant throughout the dermis and is associated with interfibrillar spaces. Type VII Forms anchoring fibrils in DEJ

39. Ultrastructure Of Collagen The molecules are made of three chains. Each chains have a helical domain consisting of (gly-X-Y) in repetition where X and Y are typically proline and hydroxy proline . On electron microscopy ,collagen is seen as regular cross striated fibrils with a 60-70nm periodicity, which is characteristic banding pattern of collagen.

40. Cross striated fibrils seen on microscopy

41. Type of collagen Sites Diseases Type I Dermis ,bones ,tendons Ehler-danlos syndrome Osteogenesis imperfecta Type III Dermis in embryonic life GI tract uterus Vascular type of ehler danlos syndrome Type IV Basement membrane of DEJ , glomeruli and blood vessels Alport syndrome Epidermal blister formation Renal insufficiency Type V On surface of large collagen fibres and regulate their growth Irregularity of individual fibre giving ‘flower like’appearance Type VII Organizes to anchoring fibrils Skin fragility in epidermolysis bullosa

42. Elastic Tissue The elastic tissue forms a continuous network throughout the dermis that extends from the lamina densa of the DEJ to the connective tissue of subcutis. Because of their elasticity, they maintain normal configuration of skin.

43. Ground substance It is the supporting matrix of dermis consisting of PGs and GAGs. Functions: Bind a large amount of water thereby influencing dermal volume and compressibility . Bind to growth factors thereby influencing proliferation ,tissue repair and morphogenesis. The major PGs in the adult dermis are : Chondroitin sulfates/dermatan sulfates (biglycan,decorin,versican) Heparan chondrotin-6 sulfate proteoglycans.

44. fibroblasts Derived from mesenchymal tissue. Most common cells found in the dermis. Function: provide a ECM framework . they synthesize and degrade fibrous and nonfibrous proteins of connective tissue and matrix. They appear as bipolar spindle shaped cells with elongated ovoid nuclei. Cytoplasm contains multiple dilated rough endoplasmic reticulum and Golgi complexes.

45. fibroblast Spindle shaped fibroblast seen on microscopy

46. Electron microscopy of active fibroblast showing abundant rough endoplasmic reticulum in cytoplasm.

47. Cutaneous Blood vessels The cutaneous vasculature is limited to dermis and epidermis has no blood vessels . Dermal vasculature is divided into two:- Superficial vascular plexus between papillary and reticular dermis. Deep vascular plexus between reticular dermis and subcutaneous fat. Vasculature regulates the body temperature by controlling the blood flow through capillaries in upper dermis so that opening blood vessels allow dissipation of excess heat and constriction slows the blood flow and conserve core energy.

48. Nerves of skin Somatic sensory fibres Sympathetic autonomic fibres Myelinated Cutaneous branches of musculocutaneous nerve innervates the skin. Responsible for sensations of touch ,pain, temperature, itching and mechanical stimuli. Unmyelinated Innervate the hair follicle ,sweat glands, arrector pili muscle and smooth muscles of blood vessels.

49. Sensory receptors Free endings Corpuscular receptors Present in papillary dermis. Have schwann cell sheath and basal lamina. Penicillate nerve endings Rapidly adapting receptors of touch , temperature,pain and itch present in hair bearing skin. Discrimination is generalised . Papillary nerve endings Free nerve endings of hair follicles Either encapsulated or noncapsulated present in epidermis and dermis. pacinian corpuscles ovoid shaped mechanoreceptors responding to vibratory stimuli. Golgi- mazzoni corpuscles Krause end bulb Meissner’corpuscles Ruffini corpuscles

50. Subcutaneous fat 80% of fat of the human body is present in the subcutis and the rest surrounds the internal organs. Fat comprises of white and brown adipose tissue. Brown fat is more common in infants and children and is characterized by different mitochondrial properties and increased heat production.

51. Subcutaneous fat Functions : Provide insulation. Provide mechanical cushioning and energy store. It also secretes leptin molecule which regulate appetite. Multipotent stem cells have also been found .

52. Thank you