1. Skin Integumentary system 2009

2. Skin (cutis, derma) The heaviest organ in the body - 16% of weight Size: 1,2-2,3m 2 Function: Protection (mechanic, from desiccation) Thermoregulation Sweat glands (perspiratio insensibilis) Sweat glands (perspiratio insensibilis) Changes in blood flow Changes in blood flow Excretion of salt (iron looses) Nonspecific immunity Metabolism- ergosterol-vit.D Sensoric ending Sexual signaling (Endocrine gland – adipose tissue: leptin, adiponectin, estrogenes)

3. Development Ectoderm Ectoderm Periderm – 2 layers cuboidal and flat superficial Periderm – 2 layers cuboidal and flat superficial Stratified squamous Stratified squamous Glands, hair and nails – invagination of ectoderm into dermis Glands, hair and nails – invagination of ectoderm into dermis

4. Skin lines (lineae distractiones) Externally visible skin lines:Externally visible skin lines: Wrinkle lines: lines of expressionWrinkle lines: lines of expression Flexure (joint) linesFlexure (joint) lines –sulcus mentolabialis, nasolabialis –sulcus gluteus

5. linea oppositionis pollicis (vitalis)‏ linea oppositionis pollicis (vitalis)‏ linea manus clausae (cephalica, naturalis)‏ linea manus clausae (cephalica, naturalis)‏ linea occlusionis dig. trium ulnarium (mensalis)‏ linea occlusionis dig. trium ulnarium (mensalis)‏ sulcus cutaneus intercarpalis (linea rasceta) sulcus cutaneus intercarpalis (linea rasceta) linea restricta linea restricta Surface pattern lines - hand – Purkyně - chiromantia

6. Skin Grooves (sulci cutis)Grooves (sulci cutis) Papillary ridges (friction ridges) (cristae cutis) – dermatoglyphics - 9 types (according to Purkyně) → daktyloscopy – forensic importancePapillary ridges (friction ridges) (cristae cutis) – dermatoglyphics - 9 types (according to Purkyně) → daktyloscopy – forensic importance Toruli tactiles – 10 in hand ( thenar)‏Toruli tactiles – 10 in hand ( thenar)‏ Lineae distractionesLineae distractiones Retinacula cutis‏ - (retinaculum caudale)‏Retinacula cutis‏ - (retinaculum caudale)‏ Intristinc scarring - Striae cutaneae – rupture of lateral cohesion of the collagen fibres -growth, pregnancy and obesityIntristinc scarring - Striae cutaneae – rupture of lateral cohesion of the collagen fibres -growth, pregnancy and obesity

7. Skin Epidermis Epidermis Dermis Dermis Hypodermis (tela subcutanea – panniculus adiposus)‏ Hypodermis (tela subcutanea – panniculus adiposus)‏ Appendages: Appendages: Hairs Hairs Nails Nails Glands of the skin Glands of the skin Mammary gland Mammary gland

8. Epidermis Stratified squamous keratinized epithelium + melanocytes, Langerhans cells, Merkel´s cells Stratified squamous keratinized epithelium + melanocytes, Langerhans cells, Merkel´s cells Thick type: palms of hands and soles of the feets Thick type: palms of hands and soles of the feets Thin type: rest of the body Thin type: rest of the body Cell renewal in epidermis:15 – 30 days EGF, Keratinocyte growth factor, retinoic acid (vit. A)

9. Epidermis Stratum basale (basophilic cuboid to columnar cells on lamina basale – stem cells) Stratum basale (basophilic cuboid to columnar cells on lamina basale – stem cells) Stratum spinosum – polygonal cells, contain of cytokeratin filament, desmosomes Stratum spinosum – polygonal cells, contain of cytokeratin filament, desmosomes Stratum granulosum – 3 – 5 layers of cells – keratohyalin granules – basophilic; lamellar granules – lipids (ceramids) – barrier – sheet containing lipid Stratum granulosum – 3 – 5 layers of cells – keratohyalin granules – basophilic; lamellar granules – lipids (ceramids) – barrier – sheet containing lipid Stratum lucidum – in thick type -eosinophilic Stratum lucidum – in thick type -eosinophilic Stratum corneum – cells filled by keratin filament are packed together by filaggrin; desmosomes Stratum corneum – cells filled by keratin filament are packed together by filaggrin; desmosomes

10. Stem cells Stem cells in the bulb region of the hair follicle – indepedent migration: Stem cells in the bulb region of the hair follicle – indepedent migration: Bulb-hair stem pathway – at the apex of the dermal papilla Bulb-hair stem pathway – at the apex of the dermal papilla Bulb-epidermis cell pathway – epidermis – stratum basale Bulb-epidermis cell pathway – epidermis – stratum basale Sebaceous glands Sebaceous glands

11. Differentiation of a keratinocyte Cells of stratum spinosum – synthesis of acylglucosylceramide – RER + GA = membrane- coating granules (or lamellar bodies) Bb. stratum granulosum – proteosynthesis = keratohyaline granules, lamellar bodies release ceramide into the intercellular spaces Bb. stratum granulosum – proteosynthesis = keratohyaline granules, lamellar bodies release ceramide into the intercellular spaces Bb. stratum lucidum – intermediate layer - eosinophilic Bb. stratum lucidum – intermediate layer - eosinophilic Bb. stratum corneum – without nuclei, keratin croslinked by filaggrin, together with ceramide form cell envelope, cells are joined by desmosomes Bb. stratum corneum – without nuclei, keratin croslinked by filaggrin, together with ceramide form cell envelope, cells are joined by desmosomes

12. Melanocytes Development from neural crest Development from neural crest Eumelanin, pheomelanin (contains cysteine) - red hair Eumelanin, pheomelanin (contains cysteine) - red hair Tyrozine – dopa – dopaquinone – melanin (tyrozinase) Tyrozine – dopa – dopaquinone – melanin (tyrozinase) Synthesis:vesicle with enzymatic activity, fine granular material Synthesis:vesicle with enzymatic activity, fine granular material Melanosome – filaments with periodocity 10nm Melanosome – filaments with periodocity 10nm Dense granule Dense granule Melanosome visible in LM, size 1x0,4  m Melanosome visible in LM, size 1x0,4  m

13. Melanocytes Cytocrine secretion melanosomes transferred to keratinocytes Cytocrine secretion melanosomes transferred to keratinocytes Function – protection from UV radiation Function – protection from UV radiation Epidermal – melanin unit – about 1000/mm2 Epidermal – melanin unit – about 1000/mm2 Higher number in the skin of scrotum, circum- anal region, areola mammae) Higher number in the skin of scrotum, circum- anal region, areola mammae)

14. Merkel´s cells Present in thick skin in stratum basale Present in thick skin in stratum basale Small dense granules (neurotransmiters) Small dense granules (neurotransmiters) Nerve ending Nerve ending Sensoric mechanoreceptors Sensoric mechanoreceptors

15. Langerhans´ cells Mainly in stratum spinosum Mainly in stratum spinosum Bone marrow derived - antigen presenting cells – in lymphatic nodes - they differentiate into activated dendritic cells – (contain Birbeck´s or vermiforms granules - rodlike) Bone marrow derived - antigen presenting cells – in lymphatic nodes - they differentiate into activated dendritic cells – (contain Birbeck´s or vermiforms granules - rodlike)

16. Dermis Dense collagen connective tissue with elastic fibres. Main glycosaminoglycane is dermatan sulphate Dense collagen connective tissue with elastic fibres. Main glycosaminoglycane is dermatan sulphate Attachment to epidermis – hemidesmosomes and anchoring filaments (laminin 5) and fibriles (collagen VI) – blister, pemphigus Attachment to epidermis – hemidesmosomes and anchoring filaments (laminin 5) and fibriles (collagen VI) – blister, pemphigus Stratum papillare Stratum papillare Stratum reticulare Stratum reticulare Skin appendages – glands, hairs, nails Skin appendages – glands, hairs, nails Sensoric ending (Vater-Paccini, Meissner etc.) Sensoric ending (Vater-Paccini, Meissner etc.)

17. Fissionability lines podle Kraisla Along the collagen fibres in dermis Important for cosmetic surgery and for cutting motion

18. Hypodermis Tela subcutanea‏ Loose collagen tissue and adipose tissueLoose collagen tissue and adipose tissue Is not present in eyelids, clitoris and penisIs not present in eyelids, clitoris and penis Retinacula cutisRetinacula cutis Panniculus adiposusPanniculus adiposus –Stratum musculorum –Stratum fibrosum Stratum membranosumStratum membranosum Textus connectivus laxusTextus connectivus laxus Bursae synoviales subcutaneaeBursae synoviales subcutaneae

19. Skin appendages Hair and hair follicle Hair and hair follicle Sebaceous glands Sebaceous glands Sweat gland Sweat gland Apocrine glands Apocrine glands

20. Hair Hair follicle Hair follicle Hair bulb (bulbus pili) Hair bulb (bulbus pili) Dermal papilla Dermal papilla Hair (cuticle of hair, cortex, and medulla) Hair (cuticle of hair, cortex, and medulla) Internal (epithelial) root sheat Internal (epithelial) root sheat External (epithelial) root sheat External (epithelial) root sheat Connective tissue sheat Connective tissue sheat Arrector pili muscle Arrector pili muscle

21. Nails Nail root hidden in nail groove Nail root hidden in nail groove Eponychium or cuticle Eponychium or cuticle Nail plate (stratum corneum) on the nail bed (stratum basale and spinosum) Nail plate (stratum corneum) on the nail bed (stratum basale and spinosum) Nail plate arises from nail matrix (root and lunula) Nail plate arises from nail matrix (root and lunula)

22. Glands of the skin Sebaceous glands – holocrine glands, composed alveolar Sebaceous glands – holocrine glands, composed alveolar Duct – stratified squamous epithelium Duct – stratified squamous epithelium Not present in thick type Not present in thick type Duct usually ends in the upper part of hair follicle Duct usually ends in the upper part of hair follicle Directly on surfacer: glans penis, clitoris, labia minora, lips, areola mammae Directly on surfacer: glans penis, clitoris, labia minora, lips, areola mammae

23. Glands of the skin Sweat glands - eccrine (merocrine) – simple coiled tubular gland Sweat glands - eccrine (merocrine) – simple coiled tubular gland Excretory duct opens at the skin surface Excretory duct opens at the skin surface Dark cells – glycoproteins Dark cells – glycoproteins Clear cells – glycogen, basolateral labyrinth – secretion of water and ionts (Na, Cl) Clear cells – glycogen, basolateral labyrinth – secretion of water and ionts (Na, Cl) Myoepithelial cells Myoepithelial cells Ducts - pseudostratified epithelium and space between keratinocytes Ducts - pseudostratified epithelium and space between keratinocytes Function - thermoregulation Function - thermoregulation

25. Glands of the skin Apocrine glands – present in axilla, anal and genitregion, areola mammae, modified in ear (ceruminous) and eyelid (glands of Moll) Apocrine glands – present in axilla, anal and genitregion, areola mammae, modified in ear (ceruminous) and eyelid (glands of Moll) Secretory part is wider, ducts opens in hair follicle, secretory activity starts at puberty (merocrine secretion with changes of cell size) Secretory part is wider, ducts opens in hair follicle, secretory activity starts at puberty (merocrine secretion with changes of cell size) Adrenergic inervation Adrenergic inervation

26. Mammary gland (glandula mammaria)‏ The greatest gland of the skinThe greatest gland of the skin Lactation → newborn nutritionLactation → newborn nutrition Paired glands – sulcus intermammariusPaired glands – sulcus intermammarius From 3th – 6 th ribs, parasternal ► anterion axillar lineFrom 3th – 6 th ribs, parasternal ► anterion axillar line Upon the deep pectoral fasciaUpon the deep pectoral fascia Retromammary space – loose connective tissueRetromammary space – loose connective tissue 11 cm x 12 cm11 cm x 12 cm 150g, during lactation 300-800g150g, during lactation 300-800g

27. Development Mammary ridge Mammary ridge Only in thoracal region (Supernumerary breasts and nipples) Development of nipple and glands Development of nipple and glands 15-20 lobes epithelial buds – lactiferous ducts 15-20 lobes epithelial buds – lactiferous ducts Before puberty lactiferous ducts and lactiferous sinuses, only Before puberty lactiferous ducts and lactiferous sinuses, only Increase in size after puberty (influence of estrogens) - terminal interlobular ducts + adipose tissue Increase in size after puberty (influence of estrogens) - terminal interlobular ducts + adipose tissue

28. Mammary gland (glandula mammae)‏ Corpus mammae – glandular tissue‏ - processus axillaris Corpus mammae – glandular tissue‏ - processus axillaris 15-20 compound tubo-alveolar glands 15-20 compound tubo-alveolar glands Ducts = lactiferous ducts → lactiferous sinuses → nipple (mammary papilla)‏ and areola Ducts = lactiferous ducts → lactiferous sinuses → nipple (mammary papilla)‏ and areola Lobes → lobules →glandular alveoles surrounded by dense connective tissue and adipose tissue ‏ Lobes → lobules →glandular alveoles surrounded by dense connective tissue and adipose tissue ‏ Fibrous condensations of stromal tissue -to the dermis suspensory ligaments (of Astley Cooper) Retinaculum cutis mammae = ligg. suspensoria mammaria Cooperi Fibrous condensations of stromal tissue -to the dermis suspensory ligaments (of Astley Cooper) Retinaculum cutis mammae = ligg. suspensoria mammaria Cooperi

29. Mamma Mamma Menstrual cycle Progesteron stimulates cyclic changes – alveolar buds develop under the influence of progesteron, old regress (apoptosis) Menstrual cycle Progesteron stimulates cyclic changes – alveolar buds develop under the influence of progesteron, old regress (apoptosis) Pregnancy – Prolactin and placental lactogen – development of secretory acini Pregnancy – Prolactin and placental lactogen – development of secretory acini

30. Lactation Nerve stimulus – oxytocin – contraction of myoepithelial cells – rejection of milk Nerve stimulus – oxytocin – contraction of myoepithelial cells – rejection of milk Prolactin – milk secretion Prolactin – milk secretion Colostrum -první mléko Colostrum -první mléko Milk – Milk – Proteins – merocrine secretion Proteins – merocrine secretion Lipids -apocrine secretion Lipids -apocrine secretion Sugar (lactosa) production in GA Sugar (lactosa) production in GA Immunoglobulins (IgA) -plasma cells Immunoglobulins (IgA) -plasma cells Decrease of prolactin level – apoptosis - regression Decrease of prolactin level – apoptosis - regression

31. Mammary gland – arteries Arcus aortae → a. subclavia → a. thoracica interna Internal thoracic artery aa. intercostales anteriores (I.-V./VI.) → rr. perforantes Arcus aortae → a. subclavia → a. axillaris Axillary artery → a. thoracica superior → (r. pectoralis a. thoracoacromialis, a. thoracica lat., a. subscapularis)‏ Aorta thoracica aa. intercostales posteriores Intercostal arteries (II.- V.) → rr. perforantes /II.

32. Mammary gland – veins Circular venous plexus Halleri – around areaolaCircular venous plexus Halleri – around areaola  v. axillaris  v. internal thoracic  vv. intercostal

33. Mammary gland - nerves nn. intercostales IV.- VI.  rami ant. + lat. sensoric (T4)‏ and sympathetic fibres

34. Mammary gland – lymph vessels 4 quadrants Plexus subareolaris Sappeyi Contralateral breast and axillaContralateral breast and axilla Internal mammary lymph node chainInternal mammary lymph node chain  nodi l. parasternales  nodi. mediastinales ant.  nodi epigastrici sup. + inf. Axillary lymph nodesAxillary lymph nodes –Sorgius – The most cranial from nodi l. pectorales,on 2./3. dens of m. serratus ant. nodi l. supraclavicularesnodi l. supraclaviculares

35. Carcinoma of mammary gland The most frequent tumor in females - 9% women suffer from this illness Clinical signs – swelling -tumor, skin pulling, ulcers Examination – palpation, sonography, mamography, lymphatic nodes exstirpation mastectomy (parcial, total)‏

36. Carcinoma of mammary gland 90% of carcinoma develop from ductal epithelium, only 10% within lobular alveolo- ductal epithelium 90% of carcinoma develop from ductal epithelium, only 10% within lobular alveolo- ductal epithelium Ductal epithelium has estrogen receptors Ductal epithelium has estrogen receptors Paget carcinoma – in the nipple Paget carcinoma – in the nipple Intraductal– within lactiferous ducts Intraductal– within lactiferous ducts Lobular carcinoma Lobular carcinoma