mod 8

Integument functions

Protection, vitamin D production, immunogenic function, sensation, thermal regulation

Integument (skin)

Epidermis and dermis

Integumentary system

Integument and its derivatives

Hypodermis

Also called subcutaneous fascia or superficial fascia

Hypodermis is NOT part of the integument

Derivatives of epidermis

Hair follicles, sebaceous glands, sweat glands, nails, mammary glands

Basement membrane

Basement laminar plus reticular lamina

Basement membrane deep to epidermis

Seen in light microscope

Basal lamina and reticular lamina seen in EM

Epidermis

keratinized stratified squamous epithelium 

stratum corneum (deep stratum lucidum in thick skin)

stratum granulosum

stratum spinosum (prickle cell layer)

stratum basale (stratum germinativum)

Dermis

loose and dense irregular connective tissue

Papillary layer

Reticular layer

EVG stain (collagen red, elastic black)

Weigert elastic stain (tissue purple, thick fibers dark purple)

Dermatoglyphics

study fingerprint

fingerprint identification

true dermal ridges are in thick skin (bases of dermatoglyphics)

Multiple dermal papillae lie between dermal ridges

Each person genetically unique

think and thin skin

refer to thickness of epithelial layer

Thickest epidermis located in hairless palms of hands and soles of feet

Stratum basale

single layer, adjacent to basal lamina, cuboidal to low columnar cells, vitamin D production, stem cells (metabolically active- only ones dividing), extensive cell junctions- desmo zone, hemidesmosome

psoriasis

Psoriasis

normal transmit time from basal cell to desquamation is 50 to 60 days, with psoriasis, rapid proliferation shortens time to about 7 days

Stratums spinosum (prickle cell layer)

Several cell layers thick

Cuboidal to squamous cells (becomes flatter)

Vitamin D production

Metabolically inactive (can't divide)

desmozones (nodes of bizzozero)

Cytoplasmic process (spines)

Stratum granulosum

One to three cell layers thick

Squamous cells (flat)

Retain nuclei

Keratohyalin granules (darker stain)

Stratum corneum (deep stratum lucidum in thick skin)

variable thickness of layer

Squamous cells

Anuclear

Keratinized cell (soft keratin)- completely keratinized as reach top

Deep stratum lucidum in thick skin

Papillary layer

Loose connective tissue

More cellular

Lots of ground substance

Loosely arranged fibers

Thin collagen fibers ( 1, 3 )

Thin elastic fibers

Reticular layer

Dense irregular connective tissue

Less cellular

Closely packed fiber bundles

Thick collagen fibers ( 1 )

Thick elastic fibers

Wound healing

Collagen and elastic fibers oriented in parallel lines called Langer lines

Surgical incisions parallel to Langer lines heal faster

stratum basale ramps up mitosis

Migrate to proliferating cells

Exfoliate of dead keratinocytes free scab

fibroblast differentiates into myofibroblast

myofibroblast involved in wound enclosure

Cells of epidermis

Keratinocytes

Melanocytes

Linker hand cells

Merkel cells

Keratinocytes

Keratinization, water barrier, cell junctions

Keratinization

Accumulation of keratohyalin granules as cells differentiate against high concentrations of keratohyalin granules in stratum granulosum

keratohyalin granules are characteristic histological features and initiate conversion of granular cells into cornified cells over 2-6 hours

Water barrier

Formed by laminar bodies that secrete pro barrier lipids and other molecules into intercellular space between stratum granulosum and stratum corneum

Cell junctions

Hemi desmosomes tether keratinocytes of stratum basale to basil lamina

Desmosomes tether keratinocytes together

Cytoplasmic process are connected by desmosomes (at light level called nodes of bizarro)

Desquamation (exfoliation ) result of pro-lytic degration of desmosomes in a pH dependent manner-desmosome keeps cells together until get to top of corneum, get more acidic decrease PH- desmosomes die → Slough off (exploration)

Hemi desmosomes

tether keratinocytes of stratum basale to basil lamina

Desmosomes

tether keratinocytes together

Cytoplasmic process are connected by desmosomes (at light level called nodes of bizarro)

melanocyte

Neural Crest derived

Migrate to stratum basale

Basophilic cytoplasm

No desmosomes- don't attach- migrate- how it gets to stratum basale

Production of melanin granules

Melanin granule transport via kinsein or dynein along microtubules (In cytoplasm of melanocyte ->kinesin-> keratinocyte pahgo-> dynein-motor molecule-transport elsewhere

Keratinocytes phagoctosis melanin processes to take up melanin granules

Number of melanocytes similar across humans, regardless of integument pigmentation, pigmentation determined by melanin degradation rate (suntan forward slow degradation of melanin)

cancer of epidermal origin

basal cell carcinoma

squamous cell carcinoma

malignant melanoma

melanocyte proliferation- dangerous

ABCD rule- asymmetrical shape of lesion, border of lesion is irregular, color variations, diameter grater than 6mm

langerhan’s cells

antigen-presenting cells (presenting to t-lymphocytes)immune system APC

originate in bone marrow and migrate to stratum spinosum

indented nucleus

no desmosome -migrate

rod-shaped Birbeck granules in cytoplasm

Birbeck granules

langerhan’’s cells express lectin langerin

langerin induces formation of Birkbeck granules

Birkbeck granules internalize and degrade HIV-1

lectin cause Birkbeck granule to form

merkel’s cell

ectoderm derived

in stratum basale

most abundant in fingertips (touch)

contain dense-cored neurosecretory granules (in contact w/neuron release granules (neurotransmitter)→ fire neuron

desmosomes tether merkel cells to keratinocytes (stable, do not move)

synapse with pseudo unipolar neurons

function in tactile sensation

merkel cell carcinoma

rare but aggressive

innervation

free never ending, merkel cell, corpuscle-Pacinian, Meissner, Ruffini

free nerve ending innervation

pain, temperature, tactile

no assocated structure

most pain, temp

all look same but each one respond to something different, increase temp or decrease temp-not both

corpuscle

have connective tissue encapsulated nerve ending

Pacinian, Meissner, Ruffini

Pacinian corpuscle

deep pressure, vibration

deeper down near hypoderm

onion looking

Meissner corpuscle

tactile

superficial her epiderm

Ruffini corpuscle

tactile

hair follicle

derived from epidermis even though extends to hypodermis

hair: medulla, cortex, cuticle

internal root sheath, external root sheath, glassy membrane (basal lamina), connective tissue, hair papilla enclosed by hair bud

cortex of hair

contain cuboidal cells

cuticle of hair

contains squamous cells

keratinized hair cells

contain hard keratin

hair color determined by

melanin content and type

glands

made of parenchyma (cells responsible for organ function-typically epithelial tissue)

stroma (cells with supporting role-typically connective tissue)

endocrine and exocrine glands

endocrine galnds

secrete hormone into stroma-hormones reach target through blood

exocrine glands

secrete products into ducts, ducts convey products to lumen or surface

merocrine, apocrine, holocrine

apocrine secretion

secretory product released from apical end of cell into duct

released with cytoplasm and plasma membrane

lactating mammary gland-compound tubuloacinar

holocrine secretion

secretory product released into duct

released with cell debris after cell apoptosis

sebaceous glands of integument- branched acinar

merocrine secretion

secretory product released from apical end of cell , exocytosis into duct

sweat gland of integument-simple coiled tubular

no plasma membrane-no enclosed, just release item

sebaceous glands

branched acinar gland

holocrine secretion of sebum

sebum

lipid product + cell debris aafte4r apoptosis

coats hair (gland next to hair)

correlation between sebum amount and acne

sweat glands

eccrine sweat glands

apocrine sweat glands

eccrine sweat galnds

widely distributed in integument (scattered)

simple coiled tubular gland

3 cell types

merocrine secretion (no apop, no membrane)innervation is SNS cholinergic -acetal choline neurotransmitter (ACh)

water-rich sweat antibacterial glycoprotein granules

narrow lumen in duct

clear cells and dark cells

clear cells

eccrine sweat glands

columnar shape

produce sweat (pater portion)

increased mitochondria and glycogen

increased surface area of plasma membrane

adjacent to intercellular canaliculi

intercellular canaliculi

eccrine sweat galnds

space connect to lumen to take things there

dark cell

eccrine sweat gland

pyramidal shape

antibacterial glycoprotein granule

increased rer and golgi

adjacent to lumen

myoepithelial cells

eccrine sweat gland

contraction assists secretion

apocrine sweat glands

primary axilla, anus, external genitalia

hair follicles

simple coiled tubular gland

one cell type

merocrine secretion

innervation is SNS adrenergic norepinephrine (NE)

protein-rich sweat which can be stored in lumen

wide lumen duct

nails

nail matrix-epidermal germinative zone

hard keratin do not desquamate (no sluff off)

eponychium=cuticle

hyponychium=thick epidermis that secures free edge of nail

ectoderm in development

gives epidermis

outermost and NS

mesenchyme in development

gives dermis

lateral place →limbs and body wall

paraxial→ back

neural crest cell→ face and neck

segmentation

with each spinal cord-”st5rip of integument”

what invigorates where

spinal cord grows out, pass though mesoderm tissue→ mesoderm becomes vertebra

lines of Blaschko

set of patters in pt with dermatological disorder

make out desmosome layers

distinct likes in every invigorated differing areas

host skin defenses

innate immune system

intact epidermis: acidic pH, low moisture, low surface temperature, salt

excreted chemicals: sebaceous glands (sebum-lipids & FA) & sudoriferous glands (salt, urea & FA)

normal microbiota-compete for sites

Langerhans cells-motile dendritic cell of epidermis (capture, transport, present antigen to T cells)

routes of infections

exogenous-disrupted sin barrier

endogenous-seeded into tissues, blood, lymph, normal microbiota

toxin induced-made at distant site-cause pathogenies in/near skin

common bacterial skin and soft tissue

G+:

staphylococcus aureus (localized abscesses)

streptococcus pyogenes (spreading infections)

Propionibacterium acnes (acne vulgaris)

clostridium perfingens

G-: pseudomonas, haemophilus, vibrio, pasteurgella

staphylococci

g+

staphylococcus aureus

staphylococcus epidermidis

staphylococcus saprophyticus

staphylococcus aureus

G+, grape cluster

B-hemolytic-lyse RBC (see though blood agar plate)

normal microbiota

localized infection-abscesses

staphylococcus aureus virulence

many cell surface and extracellular virulence factors →multifactorial

some expressed not all at one time→ multifactorial

depend on what expressed→ disease progression

cell associated virulence factors of staphylococcus aureus virulence

capsule, protein A, clumping factor

capsule of staphylococcus aureus

microcapsule, polysaccharide, serotype 5 & 8-evade phagocytosis (k antigen)

protein A of staphylococcus aureus

on surface of staph. binds to Fc region of IgG, interferes with phagocytosis and complement activation-aggregation -no Fc release/rxn, slow immune response to staph

clumping factor of staphylococcus aureus

cell bound coagulase -cell wall protein- bound to cell wall, binds to fibrinogen → fibrin=bacterial aggregation (antibody only reach outside, org still inside)

extracellular enzyme of staphylococcus aureus

coagulase (+), hyaluronidase, nucleases, lipase, catalases (+), staphylokinase, penicillinase

coagulase (+) staphylococcus aureus

free protein, not cell bound, extracellular, secreted

bind to prothrombin=staphylothrombin

converts fibrinogen to fibrin

creates localized clotting

clumping factor/coagulase

hyaluronidase and nuclease

not organism specific-chew at tissue matrix

lipases

degrades phospholipid→ tissue die

catalase (+) staphylococcus aureus

inhibits phagocytic killing interfere with myeloperoxidase system-hypochlorous acid

staphylokinase

fibrinolysis-dissolve fibrin clot

specific to staphylococcus aureus

penicillinase

B-lactamase-hydrolyzes penicillin

not virulence factor but help survive

survival with inappropriate therapy

how staphylococcus aureus penitrates

travel through blood to tissue→ clumping factor (cell-bound adhesion) converts fibrinogen to fibrin, bind to epithelium→ organism secrete coagulase (soluble), binds prothrombin, converts fibrinogen to fiber, localized clotting→ blood c lot form around clump of cells→ immune system don’t recognize as foreign→ organism release enzymes (lipases, nucleases, hyaluronidase, neuraminidase)→ once in tissue, organism secrete staphylokinase (fibrinolysin) → dissolve clot→ organism leave and infect other tissue

toxin of staphylococcus aureus

exofoliatin/ exfoliative toxins

toxic shock syndrome toxin

enterotoxin

cytotoxin (a,b,g,d)

exfoliatin or exfoliative toxin

lyse epithelial junction (desmosome)

uppe3r layers of epithelium= no scarring

toxic shock syndrome toxin (TSST-1)

cause major systemic effects, induces release of cytokines

superantigen- hyperfocus inflammation response → cytokine storm→ occupy 50% T cell to one toxin→ overwhelm immune toxin

staphylococcus aureus specific

enterotoxin

induce release of cytokines

act on natural receptors in upper GI tract

activate vomiting center

superantigen

cytotoxins (a,b,g,d)

lyse a variety of cells (erythrocytes, leukocytes, hepatocytes, platelets, smooth muscle in blood vessels)

Streptococcus pyrogenes

G+, cocci-chain

GAS/GABHS- group a, b hemolytic strep, most frequent streptococcal skin pathogen, group A-specific cell wall carbohydrate (antigen detected in rapid strep test)

spreading infection-move though body, agreessive

Streptococcus pyrogenes enzymes

Dnase, hyaluronidases, streptokinase, toxin (SPE) and virulence factor (M protein)-Spe, M protein

hyaluronidase

spreading factor in streptococcus pyogenes

streptokinase

spreading factor in streptococcus pyogenes-dissolves blood clots

Toxins (SPE)

Streptococcus pyogenes

Streptococcal Pyrogenic Exotoxins, A-C and F

erythrogenic superantigens

rash-scarlet fever

group of exotoxin secreted-superantigen in blood stream→ systemic

M protein

fimbriae/pili associated

impede phagocytosis, contribute to invasiveness

creates sequelae-antibodies to M protein cross-react with host cells, acute rheumatic fever (ARF)-generate antigen-antibody complexes-lodge in glomeruli-APSGM acute poststreptococcal glomerulonephritis

help bind to target cell and stop phagocytosis

propionibacterium acnes

G+, pleomorphic bacilli-no actual shape, # of diff forms depending on env nutrients, mostly bacilli (short chains or clumps)

common aerotolerant anaerobe (small O2), normal skin microbiota (sebaceous glands- FA)

Acne-primary bacterium

opportunistic infections in pt with prosthetic devices and intravascular lines (immunosuppressed pt)

progression of propionibacterium acnes

folliculitis→ boil→ carbuncles (direct progression from mild → severe)

discrete disease but damage accumulates during infection or by manipulation

macules

flat, non-palpable

flat, see red, not above skin, cant fell it, below surface

papules

palpble lesion

over surface of skin, feel it, painful, red

vesicles

palpable, fluid-filled lesions

sebum, feel, below and above skin

pustules

palpable, pus

pus by organism, feel, below and above, feel

abscess

localized collection of pus surrounded by inflamed tissue

abscess forming skin infections

acne vulgaris

noninflamed acne vulgaris

inflammatory acne vulgaris

folliculitis

superficial folliculitis

wetsuit folliculitis

furuncles and carbuncles

acne vulgaris

Propionibacterium acnes, G+

anaerobic, nonmotile, pleomorphic rod

normal skin microbiota (halotolerant)

commonly colonized skin, sebaceous glands