Basic Anatomical Structure of Skin Part II PDF 2024

Basic anatomical structure of skin- part-II Dr: Hamida Aldwibe Prof of D & V- 2024  TAC that can still replicate, but only for a few cycles, until they reach a termi...

Basic anatomical structure of skin- part-II Dr: Hamida Aldwibe Prof of D & V- 2024  TAC that can still replicate, but only for a few cycles, until they reach a terminal diff. phase, where they Regenerate move upwards & themselves eventually desquamate Divide & differentiate ‫هرمة‬  Stratum spinosum (Prickle) 5 -10 (8 -10) layers (multilayered)  Large nucleated supra-basal. K  Irregular shape cells Stratum spinosum (Polyhedral / Polygonal)  Round (oval) nucleus  Prominent nucleoli & cytoplasm. Dr: Hamida Aldwibe-2023  Stratum spinosum: (Prickle)  Pavement like structure (‫)الرصيف‬  Cells are bigger than basel cells  Limited cell division Stratum spinosum  Itaccompanied by more prominent tono-fibrils. Dr: Hamida Aldwibe-2023  Stratum spinosum (Prickle)  Contains:  keratinocytes  Langerhans cells (Scattered Stratum throughout the layer ) spinosum  Lamellar granules Langerhans cell  Multiple types of intercellular junctions Dr: Hamida Aldwibe-2023  Desmosome ( Prominent in st. spinosum ) A delicate spine like processes Spiny’ appearance on H&E microscopically. Ca++ dependent structures that promote cell adhesion (Desmosomal attachments bridge (sites) between cells for cytoskeleton (intermediate filaments) Dr: Hamida Aldwibe-2023 Desmosomal related Infections Bullous impetigo SSSS Stratum spinosum: (Prickle)  On moving up become:  Flatter  Develop organelles:  lamellar granules = odland bodies Stratum spinosum  Addition of keratin fibers takes place Stratum spinosum: (Prickle)  Have large bundles of keratin filaments around nucleus & inserted into desmosomes peripherally  Keratins 1 & 10 made in it K1/ K10  K5/K14 still present, but not made de novo in it K5/ K14  The keratinisation process  Consists on a series of mitotic divisions that start at the st. basale  That lead to the replacement of the cytoplasm with the protein keratin.  New synthesis of K1/K10 (keratinization)  Are specific keratins, characteristic of K1/ K10 epidermis & markers of terminal differentiation  At the end of the keratinisation process, K. can be found dead, as flat, nucleus-free & highly keratinised squamous cells at the st. cornum.  St. Germinativum (Basale)  The epidermis renews itself continuously by cell division (mitosis) in it’s deepest ( basal layer).  Renewal of the epidermis takes approximately 26 to 28 days:  13 to 14 days for maturation from basal layer to corneum &  Another 13 to 14 days for shedding Basal ( desquamation ) layer Dr: Hamida Aldwibe-2023  After a mitotic division a newly formed cell will undergo a progressive maturation called keratinization as its migrates to 26-28 days the surface. maturation  Basal cells contain: Ornithine decarboxylase ↑ ornithine decarboxylase expression (ODC) Is a marker for proliferative activity  Markers for hyper-proliferative states in st. spinosum are: k6 k16 K17 ki-67 Α3β Integrin  Recent studies  Have recognized:  Up-regulation of these keratins ( K6/ k16/ k17 ) alters:  Proliferation  Cell adhesion  Migration of KCs  Inflammatory features of KCs  Dysregulation of the innate immune response of KCs Un controled inflammation Psoriasis pathogenesis  In cases of:  Psoriasis  Actinic keratoses SCC  Wound healing  Prurigo nodularis  Supra-basal keratinocytes (st. spin0sum):  Down-regulate K1/K10 &  K6/K16/ K17 are upregulated (make) in hyperproliferative k, outer root sheath, & oral epithelium.  (mRNA always present for K6/K16/ k17, but only translated during proliferation)  Active k6, 16, 17, mRNA levels are in prurigo nodularis lesions-2021 upregulate Down-regulate upregulate K6a/K16 mutation K6b/K17 Pachyonychia congenita 1 Pachyonychia congenita 2  The expression of Ki67  Isa non histonic protein which is interfere with cell proliferation and has many controlling effects on cell cycle.  The expression level of ki67 is strongly associated with:  Cell proliferation activity  Growth (tumor cells  Disease progression  Cancer recurrence  Metastatic potential  The expression of Ki67  Ki67 is a useful poor prognostic indictor for melanoma pts.  Is higher in aggressive & recurring BCC  SCC  Gliomas  Iswidely used in routine pathological investigation as a proliferation marker at the molecular level by IHC.  Lamellar bodies known as:  Lamellar granules  Keratinosomes  Odland bodies)  Membrane-coating granules (MCGs) ( vesicles/ vacuoles )  Lamellar granules“ Odland bodies” A membrane bound intracellular structures (secretory organelles)  Are round to oval Lamellar granules  Measure approximately Odland bodies  100 to 300 nm in size (G)  0.2 – 0.3 μm (Esra)  Lamellar granules“ Odland bodies”  Formed (originate) in Golgi app.  In upper most part of spinous layer  Become more abundant in the cytoplasm of granular layers. Odland bodies  Their primary site of action is at the interface between the granular & cornified cell layers (st. corneum) Primary site of action of LG Ultrastructura of LG (transmission electron. M) Secreted LG Red arrows indicate secreted LG. Green arrows indicate LG in the cytoplasm. LG in the cytoplasm.  Lamellar granules“Odland bodies” Containing a series of alternating thick & thin lamellae (folded sheets, disk like, liposome like) Light lamellae Dense lamellae May be thick or thin Contain Contain Phospholipids Proteins Free sterols Polar lipids Hydrolytic enzymes Lameller granules (lamellated or odland bodies) contains:  Lipid  Hydrolytic & Catabolic enzymes:  Glucosyl-ceramides (predominant lipid of st. C.)  Lipases (Specific barrier lipids)  Glycosidase   Acid hydrolases  Glycoproteins  Acid phosphatases  Glycolipids  Proteases  Phospholipids  Antimocrobial peptides:  Free sterols  Beta defensins (hBDs)  Cathepsin D  Proteins (e.g. corneodesmosin)  Kallikrein (KLK7/ KLK8) Odland bodies are important for:  Epidermal permeability barrier function  Desquamation of keratinocytes   Formation of the cornified cell envelope  Odland bodies are important for:  Local anti-microbial immunity.  Recently --- a role in the local innate immune response as they contain beta 2 defensins, (anti- microbial peptides) with potent activity against Gram-negative bacteria & candida. Lamellar granules“Odland bodies”  Are specialized lysosomes (secretory) which secreted from K  Bud off (‫ )برعم‬from the Golgi Lamellar Hydrophobicgranules barrier complex lamellar sheets  Atthe transition from the G. layer to the cornified layer,  TheLG fuse with plasma. M. of K. secretory Transient cell Lamellar granules“Odland bodies”  Discharging their contents of ceramides, other lipids & enzymes into the extracellular = bricks space at the junction of the G. & cornified layer Lamellar Mortar hydrophobic granules barrier  Forms lamellar sheets = lamellar sheets (ceramide) or ‘mortar’ which acts as intercellular cement for corneocytes (‘bricks’)  Thus contributing to formation of secretory cutaneous lipid barrier  Lamellar granules “Odland bodies” ➔ Ceramides help to form the cornified = mortar = ceramide cell envelope, and eventually replace the cell membrane = Bricks  Create a hydrophobic barrier between the G. & cornified layer Mortar Lamellar = lamellar hydrophobic barrier granules  1) Water retention in the outer epidermis sheets  2) Formation of the water impervious (‫ )منيع‬barrier zone (a barrier to water loss)  Also at transition, filaggrin directs the secretory aggregation of keratin proteins  Function of LG  Have a central role in the formation of an impermeable, lipid-containing membrane (permeability) that:  Is required for maintaining skin barrier function  Mediate st. corneum cell cohesion and they form a barrier to water loss (Serves as a water barrier).  Serves as an antimicrobial barrier  Is essential for fluid & electrolyte balance.  Release components that are required for skin shedding (desquamation) in the upper most epidermal layer  Accounts for the efficacy of topical medications & for allergens to enter the epidermis & promote sensitization. Clinical implications of LG  Recent studies:  Thepathogensis of psoriasis & atopic D. may include primary abnormalities in skin barrier function  LG secretion & lipid structure is abnormal in the epidermis of pts with Netherton syndrome.  Lamellar bodies related diseases:  1) Harlequin ichthyosis:  LG or abnormal or absent.  2) Flegel’s disease: : LG  3) Congenital ichthyosiform erythroderma:  ↑ LG but structurally abnormal  4) X-linked.R. ichthyosis:  Absent steroid sulfatase in LG.  Harlequin ichthyosis = Ichthyosis congenita gravior  Harlequin ichthyosis = Ichthyosis congenita gravior Auto. R Ears are rudimentary or absent Eclabium & ectropion are severe LG or Deformities of the nose, absent or and hands/feet abnormal Thick, horny, armor- Child is often stillborn or like plates of scale premature or dies soon after with deep fissures delivery Survivors, develop features of: covering the entire - Congenital ichthyosiform surface. erythroderma or - Lamellar ichthyosis.  Harlequin ichthyosis:  Defect (mutation) in ABC lipid transporter gene (ABCA12) at C 2q34  ABCA12 encodes a membrane transporter protein of epidermal LG that is involved in energy-dependent lipid transport.  Defective also in lamellar ichthyosis type II  Abnormalexpression of profilaggrin, K6 & K16 have been reported.  Lamellar ichthyosis  Usually, a collodion -like membrane covers the baby at birth, then desquamates over the first 2–3 wks of life Scales are large & dark  Inherited as an auto. R. trait.  LG or uniformly abnormal or absent.  Mutation in TGM1 gene on C14  LI type 2 has been associated with mutations in the ABCA12 gene.  Congenital ichthyosiform erythroderma: = Non-bullous CIE = NBCIE caused by mutations in any one of at least three CIE genes: as presents ALOX12B, ALOXE3 a collodion or NIPAL4 baby at birth in about 90% of cases gradually progressing to erythroderma  LG but structurally abnormal  Together with lamellar ichthyosis (LI), it has been classified under autosomal recessive congenital ichthyosis (ARCI)  Congenital ichthyosiform erythroderma: = Non-bullous CIE = NBCIE may be caused by mutations in any one of at least  To date, three mutations genes: in at least ALOX12B, 5 genesor ALOXE3 have been NIPAL4 reported to cause CIE:  Lipoxygenase (LOX) genes (ALOXE3, ALOX12B)  NIPAL4 (ICHTHYIN)  ABCA12  TGM1  (Mutations in ALOX12B, ALOXE3 or ABCA12 genes are responsible for most of cases).   Congenital ichthyosiform erythroderma: = Non-bullous CIE = NBCIE may be Cicatricial alopecia can occur Nail dystrophy and ectropion are common. Scales are fine and white on the trunk, face, and scalp with erythema While larger and greyer on the limbs  X-linked.R. ichthyosis:  Absent steroid sulfatase in LG. (epidermis)  Steroid sulfatase deficiency (SSD) (90%)  SSD impaired hydrolysis (breakdown) of cholesterol sulfate & dehydroepiandrosterone sulfate (DHEAS) Accumulation of cholesterol 3-sulfate in epidermis  Persistent cell cohesion in upper st. C  corneocytes are not able to shed large dark brown, polygonal, adherent scales favoring the neck, preauricular area, scalp (especially in young Failure of desquamation & excess scaling children), extremities, and trunk  X-linked.R. ichthyosis  In women pregnant with an affected fetus, steroid sulfatase deficiency in the fetal placenta causes:  Low or absent levels of estrogen in the urine & amniotic fluid because of inadequate deconjugation of DHEAS  (which is necessary for estrogen synthesis).  Failure of spontaneous delivery  due to insufficient dilation of the cervix.  This can only be partially overcome by oxytocin administration, often necessitating cesarean section.  X-linked.R. ichthyosis diagnosis  Increased levels of the beta fraction of cholesterol sulfate in serum of pts can be detected by serum lipoprotein electrophoresis (screening test).   Diagnosis can be confirmed by genetic testing Cholesterol sulfate level elevated for STS mutation  Measurement of steroid sulphatase enzyme activity in leukocytes or fibroblasts or K (useful )  X-linked.R. ichthyosis diagnosis  Prenatal diagnosis (amniocentesis & CVS) can be done by:  Measurement of decreased estrogen levels &  The presence of non hydrolyzed sulfated Cholesterol sulfate level elevated steroids in maternal urine  X-linked.R. ichthyosis associations  Asymptomatic comma-shaped corneal opacities occur in 10 – 50% of male pts & in some female carriers  Otherocular abnormalities such as deuteranopia (green color-blindness) are rare.  Male pts have a 20-fold increased incidence of cryptorchidism (15%) & are at higher risk for developing testicular cancer (germ cell ca.) & hypogonadism.  X-linked.R. ichthyosis associations  There have been rare reports of:  Seizures  Reactive psychological disorders, attention deficit disorder  Developmental delay  Pyloric hypertrophy  Congenital defect in the abdominal wall  Acute lymphoblastic leukemia in pts with steroid sulfatase deficiency.  Although steroid sulfatase activity is measurably reduced in 85% of female carriers, the remaining activity seems sufficient to prevent any skin manifestations.  Epidermolytic ichthyosis  Was formerly known as:  Epidermal hyperkeratosis  Bullous congenital ichthyosiform erythroderm  It typically presents at birth with: Uncommon  Erythroderma  Skin fragility  Peeling skin  Blistering  Superficial erosions & ulceration Autosomal dominant  Epidermolytic ichthyosis  Caused by missense mutations  (where a single nucleotide is changed) in the keratin genes K1 (KRT1) and K10 (KRT10).  Spontaneous mutation occurs in 50% of cases  Mutations in KRT1 are associated with severe palmoplantar keratoderma.  Mutations in KRT10 generally lack palmoplantar symptoms.  Keratintonofilaments consist of K1 and K10 and are a robust (‫ )قوي‬structural component of the keratinocytes in the epidermis.  Mutations in KRT1 and KRT10 lead to:  1)Variable disruption and decreased stability of the K1/K10 tonofilaments  2)Hyperkeratosis due to lack of desquamation  Improvement with age  Blistering is replaced by dark-brown, grey, or white dry or macerated scales and erythema  Palmoplantar keratoderma  Common symptoms:  Anhidrosis  Pruritus  Fissuring  Decreased joint mobility  Hair, nails, and mucosal surfaces are usually not involved.  Epidermolytic ichthyosis in an adult Corrugated ridges Cobblestone pattern Skin fragility decreases over time, with development of widespread hyperkeratosis that forms corrugated ridges in flexures and a cobblestone pattern on extensor surfaces of joints Epidermolytic palmoplantar keratoderma limited to the palms and soles has mutations in the ……………. KRT9 gene  Epidermolytic keratoderma with prominent erythema at the border.(Vörner type). In general, epidermolytic and non- epidermolytic forms cannot be distinguished clinically Flegel's disease = Hyperkeratosis lenticularis perstans Rare Small red brown hyperkeratotic papules Flegel's disease = Hyperkeratosis lenticularis perstans  Pathophysiology---- is unknown  Auto. D. transmission In familial cases  Exposure to the sun has also been implicated but not proven.  Skin biopsy showed:  Dense, focal hyperkeratosis & parakeratosis  Absent. G. layer --- LG  Acanthosis  Upper dermal lymphocytic infiltrate in a band-like manner.  Disorders associated with abnormalities of Odland bodies  Function of St. spinosum: (Prickle)  Provides strength & flexibility to the skin  Synthesizes cytokeratins/ cytoplasmic intermediate filaments (= keratin fibers Stratum formation) spinosum  Desmosomes --- bridges between adjacent K & resists mechanical stress Dr: Hamida Aldwibe-2023