Pathophysiology of the Integumentary System PDF

Pathophysiology of the integumentary system Dr Elina Psara Integumentary system • Components: – Skin (integument) – Hair – Nails Fun facts about the integumentary system • • • • • • Skin is the largest organ of the body Skin comprises 12-15% of body weight Thickness: 0.5-3.0mm Nail growth rate...

Pathophysiology of the integumentary system Dr Elina Psara Integumentary system • Components: – Skin (integument) – Hair – Nails Fun facts about the integumentary system • • • • • • Skin is the largest organ of the body Skin comprises 12-15% of body weight Thickness: 0.5-3.0mm Nail growth rate: 0.1 mm/d Hair growth rate: 1.5-2.2 mm/w Life span of hair: – Eyelashes and axilla: 4 months – Scalp: 4 years Functions of the integumentary system • • • • • Protection Sensation Thermoregulation Excretion of wastes Synthesis of vitamin D Protection from (part 1/2): • Mechanical and chemical damage – Barrier of tough, keratinized cells – Pain receptors warn body of possible damage • Pathogens – Unbroken surface – Acidic secretions inhibit bacterial growth – Phagocytes ingest foreign material • UV radiation – Melanin absorbs UV light and prevents it from reaching deeper layers Protection from (part 2/2): • Thermal damage – Pain receptors warn body of possible damage • Desiccation (drying out) – Keratin and other substances keep skin fairly waterproof Sensation • Sensory receptors that can detect: – Heat – Cold – Touch – Pressure – Pain Thermoregulation • How does the skin help us cool down? – Evaporative cooling (sweating) – Increased blood flow through skin (increases heat loss) • How does the skin help us warm up? – Goose bumps: arrector pili muscles contract to pull hair upright, and add insulation to body – Decreased blood flow through skin (reduces heat loss) Excretion of wastes • The sweat glands excrete metabolic wastes: – Urea – Uric acid – Salt – Lactic acid – (Water too) Synthesis of vitamin D • When UV light hits the skin, modified cholesterol molecules are converted into vitamin D Components of the integumentary system • 2 major components: – Cutaneous membrane (epidermis and dermis) – Accessory structures (hair, nails and exocrine glands) • Does not function in isolation – Extensive network of blood vessels and sensory receptors in dermis – Hypodermis (subcutaneous layer) Organ/component Primary function Cutaneous membrane: - Epidermis - Dermis Covers surface; protects deeper tissues Nourishes epidermis; provides strength; contains glands Hair follicles Produce hair; innervation provides sensation Hair Provides protection for head Sebaceous glands Secretes lipid coating that lubricates hair shaft and epidermis Sweat glands Produces perspiration for evaporative cooling Nails Protects and stiffens distal tips of digits Sensory receptors Provides sensation of touch, temperature, pressure Epidermis • • • • Keratinised stratified squamous epithelium Outer most protective shield of body Avascular Thin skin (most of body surface) → 4 layers – Thinner layers compared to thick skin • Thick skin (lips, palms, fingertips and soles) → 5 layers Layers of epidermis • 2 names – Stratum (pl. strata) means layers – 2nd name refers to the function or appearance • In order, from superficial to deep: – – – – – Stratum corneum Stratum lucidum (in thick skin only) Stratum granulosum Stratum spinosum Stratum basale • “Come, Let’s Get Sun Burned” Stratum basale • Deepest epidermal layer • Attached to the underlying dermis along a wavy borderline • Consists (mostly) of a single row of cuboidal cells representing the youngest keratinocytes • Many mitotic nuclei – Reflects rapid cell division • Alternate name: stratum germinativum Stratum spinosum • Spinosum = prickly • Several cell layers thick • Cells contain a weblike system of intermediate filaments, which span their cytosol to attach to desmosomes • Keratinocytes appear polygonal, irregular (spiny) in shape → called prickle cells • Scattered among the keratinocytes are: – Melanin granules – Langerhan’s cells Stratum granulosum • 3-5 layers in which keratinocyte appearance changes drastically – Cells flatten – Nuclei and organelles begin to disintegrate – They accumulate: • Keratohyaline granules • Lamellated granules – Cell membranes thicken • Above this layer, the epidermal cells are too far from the dermal capillaries so they die Stratum lucidum • Few rows of translucent, flat, dead keratinocytes with indistinct boundaries and nucleus • Gummy substance of the keratohyaline granules (i.e. eleidin) clings to the keratin filaments in the cells→ cells aggregate in parallel arrays • Visible ONLY in thick skin Stratum corneum • Hard, callous layer • 23-30 cell layers thick (3/4 of total epidermis) • Keratin and the thickened plasma membranes of cells protect the skin against abrasion and penetration • Glycolipid between cells makes this layer water resistant • Composed of dead keratinocytes • Cornification means keratinized (corneocytes) • It takes 15-30 days for cells to move from S. basale to S. corneum Stratum corneum • This layer is water resistant, but not waterproof – Hypotonic (freshwater) → swell – Hypertonic (saltwater) → shrink Major cells of the epidermis • • • • Keratinocytes Melanocytes Merkel cells Langerhan’s cells Keratinocytes • Most common cells of epidermis • Produce keratin – Fibrous protein → important for protective properties of skin • Tightly interconnected by desmosomes • Arise in the deepest part of the epidermis – Cells pushed upward by the production of new cells beneath them – By the time they reach the free surface of the skin, flattened membranes with keratin – New epidermis every 25-45 days ➢ Friction rubs them off ➢ Persistent friction causes a thickening of the epidermis: callous Melanocytes • Rounded cells with dendrite-like branches • Found in the deepest layer of the epidermis • Synthesise the pigment melanin (melan = black) – Made and accumulated in membrane-bound granules called melanosomes – Melanosomes are taken up by the keratinocytes – Accumulate on the superficial side of the keratinocytes → forming a pigment shield that protects the nucleus from UV damage Langerhan’s cells • Star-shaped • Arise from bone marrow and migrate to the epidermis – In all epidermal layers but most prominent in stratum spinosum • Also called epidermal dendritic cells • Langerhan’s cells are macrophages that help activate our adaptive immune system – Their slender processes extend among the surrounding keratinocytes, forming a continuous network Merkel cells • • • • Present at the epidermal-dermal junction Shaped like a spiky hemisphere Sensory cells innervated by sensory nerves Abundant in fingertips, oral mucosa and hair follicles • Function as mechanoreceptors Concept check • Dandruff is caused by excessive shedding of cells from the outer layer of skin on the scalp. Thus dandruff is composed of cells from which epidermal layer? Concept check • Why do paper cuts hurt so bad but do not bleed? Concept check • A splinter that penetrates to the 3rd layer of the epidermis of the palm is lodged in which layer? Concept check • Why does swimming in fresh water for an extended period cause epidermal swelling? Concept check • Some criminal sand or cut skin off the tips of their fingers so as not to leave recognizable fingerprints. Would this practice permanently remove fingerprints? Why or why not? Epidermal pigmentation (skin colour) • Epidermis contains 3 pigments: – Carotene – Melanin – Haemoglobin Carotene • Orange-yellow pigment from some vegetables • Found in stratum corneum and dermis • Most apparent in light-skinned humans Melanin • Brown, yellow-brown, or black pigment produced by melanocytes • More dominant in dark-skinned humans • Highest concentration found in cheeks, forehead, nipples and genitals Haemoglobin • RBCs contain haemoglobin, which binds and transports oxygen in the bloodstream – When bound to oxygen: bright red colour • Flushed or red when blood supply is increased (e.g. embarrassed, overheated etc.) • Pale or white when blood supply is reduced (scared or nervous) • Cyanotic or blue when reduced blood supply is prolonged (extreme cold, CVD or respiratory disorders) Dermis (part 1/2) • Composed of strong, flexible connective tissue • Consists of: – – – – – Fibroblasts: cells that form the fibers of connective tissue Macrophages: protective cell capable of phagocytosis Mast cells: immune cell that initiates inflammation WBCs: protection Its semifluid matrix is heavily embedded with: ➢ Collagen: strong, fibrous (threadlike) insoluble protein ➢ Elastin: extracellular connective tissue protein ➢ Reticular fibers: supporting framework tissue Dermis (part 2/2) • The dermis binds the entire body together like a body stocking • Richly supplied with nerve fibres, blood vessels, and lymphatic vessels • Major portions of hair follicles, as well as oil and sweat glands, are derived from epidermal tissue but reside in the dermis • Critical role in thermoregulation 2 layers of dermis • Papillary: loose connective tissue, capillaries, lymphatics and sensory neurons • Reticular: “reticulum” network of collagen and elastin fibers (dense irregular connective tissue) – Accounts for 80% of the thickness of the dermis Hypodermis • Also known as the subcutaneous membrane • Also called “superficial fascia” • Adipose-rich tissue which stores fat and anchors skin • Different patterns of accumulation (male/female) Skin appendages • Derived from epidermis but extend into dermis • Include: – Hair and hair follicles – Sebaceous (oil) glands – Sweat (sudoriferous) glands – Nails • Function: Hair – Warmth – Sense light touch of the skin – Protection – scalp • Root hair plexus: – Sensory nerves surround the base of the hair – Feel every movement around every hair strand • Arrector pili muscles: – Smooth muscle innervated by sympathetic nerves – Contracts and pulls on follicle → hair stands erected ➢ The contracted muscle presses the sebaceous gland → sebum secreted – Important for fear and rage, and it insulates us when cold (traps heat close to body – goosebumps) Sebaceous glands • Oil glands that discharge an oily secretion onto hair follicles: sebum • Distributed all over dermis apart from palms and soles • Functions of sebum: – Prohibits the growth of bacteria – Lubricates and protects the keratin of the hair shaft and conditions the surrounding skin Sweat glands (sudoriferous glands) • Cover entire skin surface EXCEPT lips, external ear canal, nipples, glans penis, clitoris and labia minora • Prevent overheating • Stimulated in response to stress and heat • Mode of secretion: merocrine Sweat glands (sudoriferous glands) • Eccrine glands – Functional in early life – Total number of eccrine glands is fixed throughout life ➢ Inversely proportional to body surface area – Eccrine sweat: mostly water and NaCl • Apocrine glands – – – – Located primarily in the axilla, breasts, face, scalp, and perineum Present from birth, but secretory function begins in puberty Larger than eccrine glands; open into hair follicles instead of onto skin surface Produce a viscous, lipid-rich and potentially odorous secretion on to hair follicles • Apoeccrine glands – – – – Develop from eccrine sweat glands in late childhood and adolescence Limited distribution: found only in axillary region Distal duct connect onto the skin’s surface Produce mostly water and NaCl secretions Nails • Made of hard keratin • Grows from nail matrix Thermoregulation • How the body regulates heat loss and heat production • Heat loss has to equal heat production in order for the body temperature to stay constant – Heat loss = heat production • Regulation is controlled by mechanisms in the body, the environment, and behaviors of the individual • Hypothalamus receives info from thermoreceptors in the skin and body core Langer’s or Cleavage lines • Skin tension lines (aka Langer's lines or cleavage lines) run parallel to the collagen bundles within the dermis • Represent the natural lines along which the skin tends to split when penetrated • Incisions made parallel to Langer’s lines will gap to a lesser extent and heal with a finer scar than incisions made at right or oblique angles to them Striae distensae (stretch marks) • Linear tears in dermal collagen • Risk factors: – – – – – – Pregnancy Rapid weight gain and loss Deficiency of fibrillin Female sex Family history Race • Pathophysiology: – Linear tears in dermal collagen – Blood vessel dilation → reddish-purple stretch marks Burns • The loss of the physical barrier function of the skin opens the door to microbial invasion and can lead to infection • Causes of burn injuries: – – – – – High temperature (70%) Electricity (5%) Friction Radiation Chemicals (3%) • Severity, morbidity and mortality directly associated with: – – – – Body surface area affected Burn depth Burn location Temperature and time of exposure to heat source Pathophysiology of burns • Local response: – Zone of coagulation: ➢ Occurs at point of maximum damage ➢ Irreversible tissue loss – Zone of stasis: • Surrounding the coagulation zone • Characterised by ↓ tissue perfusion • Moderate damage = tissue is potentially salvageable – Necrosis if: prolonged hypotension, infection, or oedema – Zone of hyperaemia: • • • • Surrounding the stasis zone Dilated vessels due to inflammation ↑ blood flow to healthy tissue Tissue will recover – Necrosis only if: severe sepsis or prolonged hypoperfusion Pathophysiology of burns • Systemic response: when TBSA >30% → release of inflammatory mediators at injury site Dermatomes • Bilateral region of skin innervated by a pair of spinal nerves • 30 dermatomes: 31 spinal nerves – C1 has no corresponding dermatome • Dysfunction or damage to a spinal nerve root can trigger symptoms in dermatome Herpes viruses • Lifelong infection that produces vesicles/blisters • Signs and symptoms come and go – Risk factors for flares: ↑ stress and ↓ immunity • Some herpes types: – – – – Herpes varicella (aka chickenpox) Herpes zoster (aka shingles) Herpes simplex 1 Herpes simplex 2 Herpes varicella aka chickenpox • >90% of cases: children <10 y • Benign in healthy children; ↑ in morbidity in adults and immunocompromised patients • Pathophysiology: – Acquired through inhalation of airborne respiratory droplets or through conjunctiva – Replication in nasopharynx and regional lymph nodes – Primary viraemia 4-6 days after infection – Multiple organs infected – Secondary viraemia with viral skin infection after replication – Varicella will permanently live in the sensory ganglia: latency following primary infection; replication suppressed → noninfectious Herpes zoster aka shingles • Result of reactivation of latent varicella infection • Reactivation → formation of virions in involved sensory neurons • Virions travel to epithelial cells → rash within corresponding dermatome • Risk factors: – – – – – Ageing Stress Immunosuppression Intrauterine exposure to varicella History of varicella at <18 months Herpes simplex virus • • • • HSV-1 and HSV-2 Double-stranded DNA virus Prevalence: 65-90% Transmitted by direct contact with an affected individual • Risk factors: – – – – Sun exposure Stress Immunosuppression Physical trauma Human papilloma virus • Small, double-stranded DNA virus: >200 types • Transmitted by skin-to-skin and skin-to-mucosa contact – Sexual and non-sexual courses (highly contagious) • CDC: “~80% of women and 90% of sexually active men, at a particular time of their life, will be infected with ≥1 HPV type” • Infects basal squamous epithelium = skin and mucosae of anogenital tract, hands or feet • HPV does not enter the bloodstream: infection does not affect other body parts • Most HPV infections resolve spontaneously within 1-2 years • A subset of HPV types (e.g. HPV-16, HPV-18) may cause cervical cancer (99%) Fungal infections (aka mycosis) • Tinea: general term for fungal skin infections • Usually located in moist areas where skin surfaces meet (e.g. genital area, between toes) • Many fungi live only in stratum corneum • Risk factors: – – – – Obesity Diabetes Poor circulation Immunosuppression Bacterial infection: cellulitis • Cellulitis is an acute, spreading bacterial infection of the dermis or subcutaneous layer of the skin • It may follow damage to skin (e.g. animal bite, wound, surgery) • Caused by streptococcus and staphylococcus – Immune cells (e.g. neutrophils) are overwhelmed • Risk factors: – Diabetes – Immunosuppression – Poor circulation Bacterial infection: Lyme disease • Commonly caused by: – Borrelia burgdorferi: USA – Borrelia afzelii, Borellia garinii, and Borellia burgdorferi: Europe and Asia • Onset usually in summer and fall • Pathophysiology: – Bacterium enters the skin at site of tick bite – After 3-32 days, organisms migrate locally in skin around bite and spread via lymphatics or blood – Inflammatory reaction (erythema migrans) occurs before significant antibody response (serologic conversion) Decubitus ulcers • Aka bedsores or pressure ulcers • Skin and soft tissue injuries forming due to constant or prolonged pressure exerted on skin • Occur at bony areas (e.g. ischium and sacrum) Alopecia • Any type of hair loss and can be acute or chronic • Immune system mistakenly attacks hair follicles → inflammation • Causes: – – – – – – Genetics Chemotherapy Hormonal imbalance Scale infections Severe emotional or physical stress Medications Scabies • Infestation of skin by the mite Sarcoptes scabiei • Pathophysiology: – Microscopic mites burrow into the upper layer of skin to lay eggs – Eggs hatch in 3-4 days; reach adulthood in 1-2 weeks – After 4-6 weeks, allergic reaction to mite proteins and faeces – Newly hatched mites (i.e. larvae) move to skin’s surface and spread over the body by scratching – Mites mate and start process over again • Anyone can get them • Contagious: by close physical contact and sometimes sharing clothes/bedding with infected person Acne • Hair follicles become clogged by sebum and dead skin cells → pimples/zits Boil (furuncle) • A painful, pus-filled bump in the skin that is caused by a bacterial infection – Staphylococcus aureus • Involves the dermis and subcutaneous tissue • A carbuncle is a cluster of boils that form a connected area of infection under the skin Contusion aka bruise • Caused by an impact of the skin, without the skin surface breaking • Small blood vessels tear → blood leaks under skin • Causes: – – – – – Sports injury Car accidents Falls Assault Domestic violence Eczema • Pathophysiology: – Caused by genetic predisposition to allergies – The epidermis is made with a defect in filaggrin protein → defective skin barrier – Skin surface is dry and cracked – Allergens hat would normally not be seen by the immune system get into the cracks – Dendritic cells (APCs) present the allergen to the immune system → generation of an allergic reaction Folliculitis • Inflammation of the hair follicles • Most commonly caused by bacterial infections (especially staphylococcus aureus) Hives (urticaria) • Pathophysiology: – Caused by an allergic reaction to external agents – Release of histamine and other vasoactive substances from mast cells in the superficial dermis – Results in intradermal oedema caused by capillary and venous vasodilation and occasionally caused by WBC infiltration Keloid • Benign fibrous proliferations that occur in the dermis after trauma or injury to the skin • They grow beyond the boundaries of the original wound size • Aetiology: unknown Skin cancer • Most common type of cancer • Out-of-control growth of abnormal cells in the epidermis due to unrepaired DNA damage that triggers mutations • Cause: UV radiation • 2 types: – Benign ➢ Does not spread (encapsulated) – Malignant ➢ Metastasised to other parts of the body Basal cell carcinoma • • • • • • • Least malignant Most common skin cancer ↑ in incidence rates Incidence ↑ with age Arises from Stratum basale Develops in body parts exposed to sun Metastasis is rare Squamous cell carcinoma • Malignant tumour of epidermal keratinocytes that invades the dermis • Arises from Stratum spinosum • Metastases occur in advanced stages • Occurs in sun-exposed areas • Incidence ↑ with age Malignant melanoma • A tumor produced by the malignant transformation of melanocytes • Melanocytes are derived from the neural crest: melanomas can arise in other locations (e.g. G.I.T. and brain) • Caused by excessive exposure to sunlight • Incidence ↑ with age Psoriasis • A chronic, noncontagious immune-mediated disease that causes rapid buildup of keratinocytes – Tenfold ↑ in cell multiplication IL-17 IL-22 IL-23 TNF-α IFN-γ Psoriasis • A chronic, noncontagious autoimmune disease that rapid buildup of keratinocytes – Tenfold ↑ in cell multiplication • Pathophysiology: – Activation of T cell by an unknown antigen → release of inflammatory mediators – Also, infiltration of skin by activated T cells stimulates proliferation of keratinocytes – Keratinocyte hyperproliferation causes raised, scaly patches on skin Questions?