Apocrine & Sebaceous Glands

• Apocrine glands are mainly in the axillae, breast, anogenital region, external auditory canal, and eyelids
• These glands secrete via decapitation, where a portion of the cell pinches off
• They primarily respond to sympathetic adrenergic stimuli

Sebaceous Glands

• Found as outgrowths from hair follicles
• Composed of pale-staining cells with lipid vacuoles, using holocrine secretion
• Holocrine secretion involves sebocyte distention until rupture
• Sebaceous glands are throughout the skin except palms and soles

"Free" Sebaceous Glands

• Glands of Zeis on the superficial eyelid margin
• Meibomian glands on the tarsal plate of eyelids
• Montgomery tubercles on the nipple and areola
• Tyson's glands on the external fold of the prepuce
• Fordyce spots on the lips and buccal mucosa

Sebaceous Gland Info

• Glands have adrenergic hormonal control
• They enlarge at puberty due to increased androgens
• Sebum composition is 57% triglycerides, 25% wax esters, 15% squalene and <3% cholesterol and cholesterol esters

Sensory Receptors

• Sensory receptors are either corpuscular or free nerve endings
• Sensory receptors are positive for S100 and contain neurofilaments
• Types of corpuscular endings: nonencapsulated (Merkel cells) and encapsulated (Meissner's and Pacinian corpuscles)
• Nociceptors detect pain via Aδ-type (large) or C-type fibers

Non-Encapsulated Endings

• Free nerve endings are rapidly adapting receptors
• Most are non-myelinated C-type fibers and some myelinated Aδ-type fibers
• Terminal endings are in the epidermis and papillary dermis and detect touch, pressure, and pain
• Merkel cells are in the basal layer, making contact with a sensory nerve terminal and detects touch

Encapsulated Endings

• Vater-Pacini corpuscles are rapidly adapting mechanoreceptors in the deep dermis/subcutis that detect deep pressure and vibration
• They are concentrated in palms, soles, nipples, and the anogenital region
• Meissner's corpuscles are elongated mechanoreceptors for light touch in the dermal papillae, with the highest density in palmoplantar skin
• Ruffini corpuscles are thin, encapsulated, fluid-filled slow adapting receptors in the deep dermis that detect continuous pressure

Mucocutaneous End Organs

• Mucocutaneous receptors are on the vermilion lip, perianal region, glans penis, clitoris, and labia minora

Elastic Tissue

• Elastic tissue makes up 4% of the skin's dry weight, and provides elasticity
• The continuous network spans from the lamina densa of the DEJ throughout the dermis
• Included are oxytalan fibers, thin fibers running perpendicular to the skin surface in the papillary dermis
• Eluanin fibers are thicker fibers parallel to the skin surface in the reticular dermis
• Elastic tissue is an aggregate of elastin and protein filaments (fibrillin)
• Desmosine and isodesmosine are unique to elastic fibers
• Lysyl oxidase is necessary for the formation of elastic-specific amino acids and cross-linking
• UV radiation damages elastic fibers
• Dermal elastosis is a hallmark of photodamage

Ground Substance

• Ground substance is amorphous gel-like material in which connective tissue fibers are embedded
• Primarily composed of proteoglycans
• Functions include water absorption, shock absorption, and lubrication between collagen and elastic fibers
• Aging increases dermatan sulfate and decreases chondroitin sulfate
• Pathological accumulation is seen in acid mucopolysaccharidoses due to deficiency of lysosomal hydrolases that normally cleaves GAGs

Glomus Cells

• They are modified smooth muscle cells in the dermis
• They allow shunting of blood from arterioles to venules without capillaries
• A glomus body consists of an afferent arteriole, Sucquet-Hoyer canal, efferent arteriole, and nerve fibers

Eccrine Glands

• The most important function is to regulate body temperature through evaporative heat loss
• They are composed of the acrosyringium, straight duct, and secretory eccrine coil
• The acrosyringium has an intraepidermal spiral duct opening to the surface of the skin
• The straight duct is within the dermis, consisting of double layer cuboidal epithelium lined by eosinophilic cuticle on the luminal side
• The secretory eccrine coil is within the deep dermis/subcutaneous fat
• It consists of glycogen-rich, pale cells and smaller darker cells
• The outer portion contains myoepithelial cells
• The glands are positive for S100, keratin, and carcinoembryonic antigen (CEA) and are found everywhere except the clitoris, glans penis, labia minora, external auditory canal, and lips
• Eccrine glands possess cholinergic innervation but are derived from sympathetic outflow, so they are functionally cholinergic but anatomically sympathetic and use merocrine secretion

Merkel Cell

• Ectoderm-derived cell functioning as a mechanoreceptor (slow adapting type 1), found among basal keratinocytes
• Found in areas with high tactile sensitivity (lips, fingers, ORS of hair follicle, oral mucosa)
• EM shows microvilli at the cell surface with dense core granules, lobulated nucleus, and intermediate filaments assuming a whorled arrangement near nucleus
• Markers include cytokeratin (CK) 20 and CK8, 18, and 19
• It contains neuron-specific enolase (NSE), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), chromogranin A, synaptophysin, and met-enkephalin

Dermis

• Mesoderm-derived components
• The dermis is divided into the superficial papillary dermis and the deep reticular dermis
• The reticular dermis has larger collagen bundles and mature, branching elastic fibers

Collagen

• Collagen is a family of fibrous proteins that provide structural stability
• Collagen accounts for 70-80% dry weight of dermis
• It is composed of 3 chains combined into a triple helix containing Gly-x-y repeats
• Collagen is degraded by interstitial collagenases (metalloproteinases or MMPs) and stimulated by retinoic acid
• Collagen synthesis is inhibited by IL-1, glucocorticoids, IFNy, TNFα, D-penicillamine, and UV irradiation

Hemidesmosome

• It appears as a thickened area interspersed along the plasma membrane of a basal keratinocyte and provides attachment between basal keratinocytes and the extracellular matrix
• Composed of BPAG1, BPAG2, integrin, and plectin
• Tonofilaments insert into hemidesmosomes

BPAG1

• BPAG1 is an intracellular glycoprotein in the plakin family and promotes adhesion of intermediate filaments with the plasma membrane

BPAG2

• BPAG2 is a transmembrane protein belonging to the collagen family and interacts with BPAG1, β4 integrin, and plectin
• Three target antigens are seen in cicatricial pemphigoid (CP): BPAG2, laminin-5 (epiligrin), and α6β4 integrin

Integrin

• Integrin is a transmembrane cell receptor consisting of two subunits (α and β) located at the basal layer of the epidermis and promotes both cell-cell and cell-matrix interactions
• α6β4 binds intermediate filaments intracellularly, laminin-5 (now called laminin-332) in lamina lucida, and HD proteins (plectin, BPAG2)

Plectin

• Plectin is an intracellular protein belonging to the plakin family that links intermediate filaments to plasma membrane and cross-links HD proteins

Lamina Lucida

• The lamina lucida is an electron-lucent zone under a hemidesmosome on EM and is the weakest link of the BMZ
• It is comprised of anchoring filaments (laminin-332), laminin-1, fibronectin, nidogen (entactin), uncein and a portion of BPAG2

Anchoring Filaments

• Anchoring filaments are delicate filaments emanating perpendicularly that stretch from plasma membrane to lamina densa
• They are a product of basal keratinocytes
• Laminin-332 is a glycoprotein serving as a major component of anchoring filaments and major attachment factor for keratinocytes and binds α6β4 integrin at the hemidesmosome

Lamina Densa

• Electron-dense zone below lamina lucida appearing as a dense line with closely stippled dots on EM
• Type IV collagen is the major component and characteristic collagen of BMZ that provides flexibility
• Additional components include laminins, entactin (nidogen-1), and heparan sulfate

Sublamina Densa

• Contains anchoring fibrils, anchoring plaques, elastic microfibrils, and linkin

Anchoring Fibril

• Primary constituent is type VII collagen, connects lamina densa to anchoring plaques in dermal matrix
• Type VII collagen autoantibodies are in both EB acquisita (EBA) and bullous SLE

Anchoring Plaque

• Primary component is type IV collagen, site where anchoring fibrils attach from above and fibrillar collagen attach from below

Melanocytes

• Pigment-producing dendritic cells derived from the neural crest that are found in the skin, hair, uveal tract of eye, leptomeninges, and inner ear
• Reside in the basal layer with a ratio of 1 melanocyte to 10 basal keratinocytes
• Function is production of melanin which protects from UV radiation
• Melanin is synthesized in a melanosome and has two types of pigment

Pigments

• Pheomelanin is red-yellow, synthesized in spherical melanocytes
• Eumelanin is brown or black, synthesized in oval-shaped melanocytes
• Keratinocytes absorb melanin leading to protection from UV-induced mutations

Hair Follicle

• Longitudinal sections have infundibulum, isthmus, and inferior segment
• Cross-sections have glassy membrane, outer root sheath (ORS), inner root sheath (IRS), cortex and the bulb
• Anagen is the active growth period, catagen is the transitional period, and telogen is the resting period
• Average hair growth is 0.35 mm per day

Langerhans Cell

• Bone marrow-derived dendritic cell with a monocyte-macrophage lineage found in the stratum spinosum that recognize and presents antigens to specific T lymphocytes
• Connected to keratinocytes via E-cadherin receptors
• On EM, Langerhans cells have a folded nucleus and distinct intracytoplasmic organelles (Birbeck granules)