Lecture N7 Integumentary System

Copyright Pass NPLEX 20181

INTEGUMENTARYSYSTEM

INTEGUMENTARY SYSTEM

▪Embryology & Anatomy▪Physiology▪Biochemistry▪Pathology (With General Overview)

SAMPLE CASE 174 year-old male presents with painful blisters. He reports them starting in hismouth and then appeared on his back and abdomen. He is diagnosed withpemphigus vulgaris.

1. Which of the following best describes the pathogenesis of this condition?

a) autoimmune attack against desmoglein 1

b) autoimmune against type XVII collagen of hemidesmosomes

c) mutation of the keratin gene resulting in a lack of connection between theepidermis and dermis.

d) defect in type V collagen synthesis

▪ Answer: A – autoimmune attack against desmoglein 1▪ This disease can involve the autoimmune attack against desmoglein 3 as well.

SAMPLE CASE #24 year-old female presents with a pruritic rash all over her body that started 2 daysago. You notice some of the lesions have begun to crust over. She is diagnosedwith varicella zoster infection.

1. Varicella zoster is a _______________ virus.

a) Single-stranded RNA

b) DNA enveloped

c) Double-stranded DNA

d) RNA enveloped


▪ Answer: B. The varicella zoster virus is a DNA enveloped virus.

EMBRYOLOGY & ANATOMY▪ Embryology

▪ Anatomy▪ Layers of the Skin

▪ Epidermis▪ Dermoepidermal Junction▪ Dermis▪ Hypodermis

▪ Sensory Receptors▪ Lipid Bilayer▪ Intercellular Junctions

EMBRYOLOGY▪ Ectoderm

▪ Epidermis and dermal appendages

▪ Mesoderm▪ Dermis and hypodermis

▪ Neural Crest Cells▪ Migrate into the skin and become melanocytes

EPIDERMIS▪ Stratified squamous epithelium

▪ Composed of keratinocytes, melanocytes, Langerhans cells, Merkel cells

▪ Basement membrane separates it from the dermis

Layers:▪ Stratum basale – on the basement membrane.

▪ Melanocytes and keratinocytes are found here.

▪ Stratum spinosum – partially keratinized cells▪ Cells in this layer are mechanically attached to desmosomes

▪ Stratum granulosum – dead cells pushed from stratum spinosum▪ Stratum lucidum – dying cells, translucent▪ Stratum corneum – fully formed keratin, cells are flattened

EPIDERMAL CELL TYPESKeratinocytes

▪ Found in the basement membrane▪ These cells mature and harden as they move up▪ They eventually die and are shed.

Melanocytes▪ Produce brown pigment.▪ Found in the inner layer of the epidermis.

Langerhans cells▪ Antigen-presenting dendritic cells▪ They are present in all layers of the epidermis except the stratum corneum.▪ Most prominent in the stratum spinosum.

Merkel cells▪ Found near nerve ending▪ Function as touch receptors

DERMOEPIDERMAL JUNCTIONHemidesmosome

▪ Found on keratinocytes▪ Connects them to the basement membrane

Basal Laminar▪ Composed of lamina lucida and lamina densa

▪ Contain anchoring proteins and cross-linking fibers, respectively


Epidermal Layers

Image: Wikimedia Commons - Author: OpenStax College

Image: Wikimedia Commons – Author: unknown

▪ Contains strong and flexible connective tissue.

▪ Cells types include: fibroblasts, macrophages, mast cells andWBCs

Layers▪ Papillary layer (thin)

▪ Contains Meissner’s corpuscles (free nerve endings), fibroblasts, blood vessels, collagen

▪ Reticular layer (thick)▪ Form Langer’s lines of tension within the skin.▪ Contains collagen and elastin fibers.

▪ Hair follicles are lined with stratified squamous epithelium

▪ Sebaceous glands are primarily attached to the top of hair follicles and produce sebum.

▪ Pilosebaceous unit is composed of hair follicle, sebaceous gland, and arrector pili muscle.

▪ Eccrine (merocrine) sweat glands are involved in moving sweat out of the body.

▪ Apocrine sweat glands are the same as the eccrine glands in structure but found only in thepubic, axillary, and perianal areas and are associated with body odor.

DERMIS

▪ Thickest layer of skin

▪ Composed of mainly adipose and areolar connective tissue

▪ Adipocytes are the primary cell type since its main function is fat storage.▪ Fibroblasts and macrophages can be found in this layer as well

▪ Not present in the following locations:▪ Eyelids, genitals, nipples, and shins

HYPODERMIS Layers of the Dermis

Image: Wikimedia Commons - Author: Blausen.com staff. " Blausen gallery 2014". Wikiversity Journal of Medicine. DOI:10.15347/wjm/2014.010. ISSN 20018762.

SENSORY RECEPTORSMeissner’s corpuscles

▪ Deep within the skin▪ Very sensitive to touch▪ Fingers and lips

Pacinian corpuscles▪ Respond to pressure

LIPID BILAYERPhospholipids

▪ Head = polar, charged, hydrophilic▪ faces towards the surface of the membrane

▪ Tail = non-polar, uncharged, hydrophobic▪ composed of fatty acid chains that face theinside of the bilayer

Cholesterol▪ Found between phospholipids▪ Maintains membrane fluidity.

Carbohydrates, glycolipids, glycoproteins▪ Found on the external membrane surface▪ Facilitate cell-cell recognition.

Image: Wikimedia Commons Author:OpenStax - https://cnx.org/contents/[email protected]:fEI3C8Ot@10/Preface


Functions▪ Transport proteins▪ Enzymes▪ Receptor sites▪ Sites for cell adhesion▪ Attachment for cytoskeleton to the membrane

Integral▪ Amphipathic and therefore span the entire membrane▪ Ex: ion channels and transport proteins

Peripheral▪ One side of the membrane▪ Anchored to the bilayer via electrostatic interactions with the phospholipids▪ Ex: hormone receptors

Secreted▪ Produced in the cell and transported out (i.e. hormones)

PROTEINSINTERCELLULAR JUNCTIONS▪ Tight junctions (zonula occludens)

▪ Found at apical surfaces, close the intercellular space▪ Prevent free diffusion of substances between epithelial cells

▪ Belt desmosomes (zonula adherens)▪ Around the entire cell▪ Creates a small intercellular space containing cadherins

▪ Desmosomes (macular adherens)▪ Allows a small intercellular space▪ Found in epithelial areas where mechanical forces are high.

▪ Gap junctions▪ Very small intercellular space▪ Consist of tubular channels which allow for communication between cells

PHYSIOLOGY

PHYSIOLOGY▪ Cellular Transport

▪ Osmosis, osmolarity, osmotic pressure

▪ Ion channels

▪ Action potential

▪ Thermal physiology and regulation

CELL TRANSPORTSimpleDiffusion

▪ No need for energy expenditure or a carrier protein▪ Concentration gradient drives it

FacilitatedDiffusion▪ Passive transport▪ Involve a protein carrier because molecules are too large topass through pores located in the membrane.

▪ Carrier proteins are highly selective and can becomesaturated.

▪ Ex: glucose carriers

Active Transport

▪ Uses energy to move a substanceagainst its concentrationorelectrochemicalgradient.

▪ Requires a carrier protein that can become saturated.

▪ Examples:▪ Primary active transport = Na+/K+ ATPase▪ Antiports▪ Symports▪ Secondary active transport where no ATP is expended (Na+-glucose transport).

Image: Wikimedia Commons –Author: Lhunter2099

Image: Wikimedia Commons – Author: Blausen.com staff.“Blausen gallery 2014". Wikiversity Journal of Medicine.DOI:10.15347/wjm/2014.010. ISSN 20018762.

Osmosis▪ Diffusion of water across a semi-permeable membrane from a low concentration ofsolute to a solution with a high solute concentration.

Osmolarity▪ Total solute concentration of a solution.

Osmotic Pressure▪ Driving force for the movement of water across a membrane.

▪ Isotonic – same concentration of solutes inside the cell as normal extracellular fluid.▪ Hypotonic – less solute outside the cell than normal extracellular fluid▪ Hypertonic – more solute outside the cell than normal extracellular fluid

Image: Wikimedia Commons – Author: LadyofHats


ION CHANNELS▪ Size selective

▪ Open or closed

▪ Voltage-gated▪ Activated by a change in membrane potential

▪ Ligand-gated▪ Activated by a hormone or second messenger

ACTION POTENTIAL▪ Restingmembrane potential of a neuron = -70 mV

▪ A transient change in membrane ion permeability allows certain ions tomove down their concentrationgradient.▪ Requires a sodium-potassiumpump

Resting state▪ Open channels are predominantly permeable to K+

Depolarization▪ Results from the opening of voltage-gatedNa+ channels which increases the membrane permeability to sodiumallowing Na+ to move into the cell.

▪ The membrane potential approaches+60 mV during this phase.▪ A threshold exists that allows the voltage-gatedNa+ channels to open and thus trigger an action potential.

Restoration▪ Closure of theNa+ channels and opening of K+ channels causes a flux of K+ out of the cell.▪ Hyperpolarization occurs for a short time during this phase,

Image: Wikimedia Commons – Author: Original by en:User:Chris 73, updated by en:User:Diberri, converted to SVG by tiZom

THERMAL PHYSIOLOGYBasal Metabolic Rate (BMR)

▪ When at mental and physical rest (not sleeping) at a comfortable room temperature and fasting for at least 12hours.

Shivering▪ Triggered by falling skin temperatures and facilitated by the hypothalamus.

Radiation▪ All objects emit heat and the rate is determined by the temperature of the radiating surface as well as thetemperature difference between surfaces.

Conduction▪ Heat is lost or gained during collision of adjacent molecules

Convection▪ Heat is lost or gained through the movement of air or water.

Evaporation▪ Water absorbs enough heat to escape as a gas.

THERMAL REGULATIONHypothalamus

▪ Center for thermoregulation▪ Peripheral receptors on the skin alert the hypothalamus.

▪ Vasoconstriction or vasodilation occurs as a result.

Fever▪ Hypothalamic set point is altered temporarily.▪ Mediated by endogenous pyrogens (IL-1, IL-6, TNF) and prostaglandins.

BIOCHEMISTRY


BIOCHEMISTRY▪ Collagen

▪ Melanin

▪ Antioxidants

▪ Cell Cycle

COLLAGEN▪ 30% glycine, 10% proline

▪ 90% = type I-III▪ I = skin, tendons, ligaments, blood vessels, organs, bone▪ II = cartilage▪ III = reticular connective tissue▪ IV = basement membrane▪ V = interstitial tissue, hair, placenta

▪ Hydroxylation of lysine and proline by lysyl and proline hydroxylase▪ Requires vitamin C and iron

Lysyl oxidase (protein-lysine 6-oxidase – PL6O)▪ Found in fibroblasts▪ Reaction results in the spontaneous cross-linking of collagen and elastin fibers athydroxylysine residues.

▪ Cofactors: copper, vitamin C

Prolyl oxidase▪ Found in fibroblasts▪ Cofactors = iron, vitamin C

MELANIN▪ Pheomelanin (orange/red/light brown pigment)

▪ Nipples, lips, glans penis, vagina

▪ Eumelanin (dark pigment)▪ Absorbs UV light

Tyrosinase▪ Found in melanocytes, neurons▪ Forms dopaquinone which is then converted to either pheomelanin or eumelanin▪ Requires: copper, tyrosine

ANTIOXIDANTSGlutathione

▪ Synthesized from glutamate, glycine, and cysteine▪ Cofactor required: selenium

▪ Gamma-glutamylcysteine combines glutamate and cysteine.▪ Glutathione synthetase combines gamma-glutamylcysteine and glycine to form reduced glutathione(GSH)▪ BOTH are dependent on magnesium

▪ Detoxification▪ Glutathione-S-transferase (GST) attaches GSH to electrophilic compounds and plays a major role in the phase IIdetoxification pathways founds in the intestines, liver, and kidneys.

▪ An inactivated and water soluble complex which can be excreted in the urine is the result.▪ Requires: selenium

▪ Redox▪ Glutathione peroxidase binds two glutathiones (GSH) together to form glutathione disulfide (GSSG), oxidizedglutathione. This reaction removes H2O2▪ Requires: selenium

▪ Glutathione reductase is involved in the regeneration of reduced glutathione (GSH)▪ Requires: NADPH

Carotenoids▪ Quench singlet oxygen and free radicals in lipid membranes and inside cells.

Flavonoids▪ React with free radicals

Alpha-lipoic acid▪ Electron carrier▪ Co-factor to pyruvate dehydrogenase complex and redox reactions.

Coenzyme Q10▪ Mediates electron transport and provides hydrogens in order to eliminate lipid peroxylradicals.


Image: Wikimedia Commons – Author: Kelvinsong

GENERAL PATHOLOGY▪ Adaptive changes

▪ Cellular injury

▪ Pigmentation

▪ Chemical mediators

▪ Complement

▪ Healing mechanisms

▪ Edema

▪ Hemostasis

▪ Wound Healing

ADAPTIVE CHANGESHypertrophy

▪ Cells increase in size▪ Often in response to increased functional demand or hormones

Hyperplasia▪ Increase in the number of cells▪ Due to increased functional demand, hormones, or persistent cellular injury.

Atrophy▪ Cells shrink in size due to persistent injury or lack of nutrients, use, oxygen, or hormones.

Metaplasia (premalignant)▪ Change from one type of tissue to another due to persistent cellular injury.

Dysplasia (premalignant)▪ Abnormal tissue development▪ Reversible if cause is removed

CELLULAR INJURYReversible

▪ Decrease in pH and pump failure▪ Fatty change

Irreversible▪ Necrosis

▪ Coagulative: Often a result of ischemia and involves proteins being denatured or coagulated.▪ Liquefactive: The result of bacterial infection and involves the destruction of tissue by lysosomal enzymes.▪ Caseous: Most commonly seen in tuberculosis granulomas.▪ Gangrenous: Result of ischemia to a lower extremity or the bowel.▪ Enzymatic fat necrosis: Complication of pancreatitis.▪ Fat necrosis: Result of severe injury to a tissue with high fat content.▪ Fibrinoid: Fibrinogen, complement, immunoglobulin, and other proteins are deposited in the arteries.

Apoptosis▪ Programmed cell death; normally after approximately 50 cell divisions▪ Cancer

▪ bcl-2 gene produces an enzyme that blocks apoptosis and immortalizes affected cells.▪ p53 tumor suppressor gene is missing or mutated in about 50% of all human cancers and prevents apoptosis.

PIGMENTATIONHemosiderin

▪ Yellow-brown granules of iron bound to ferritin▪ Hemosiderosis is seen in genetic hemochromatosis and recurrent internal bleeding.

Melanin▪ Formed from the oxidation products of tyrosine in melanosomes in epidermal cells

Lipofuscin▪ Yellow-brown pigment granules as a result of lysosomal digestion found in the adrenal glands,ganglion cell, kidneys, liver, and heart muscle.

Bilirubin▪ Yellow bile pigment found as sodium bilirubinate or as an insoluble calcium salt in gallstones.▪ Excess bilirubin is associated with jaundice.

CHEMICAL MEDIATORSCyclooxygenase Pathway

▪ Generates prostaglandins, prostacyclin, and thromboxanes▪ COX-1 is always expressed while COX-2 is expressed during inflammation .

▪ Prostaglandins (PG)▪ Produced during inflammation by endothelial and inflammatory cells as well as platelets.▪ Many of these cause vasodilation.

▪ Prostacyclin (PGI)▪ Produced by undamaged endothelial cells▪ Causes vasodilation and inhibits platelet aggregation.

▪ Thromboxanes (TX)▪ Produced by platelets.▪ Cause vasoconstriction and promote platelet aggregation.


5-Lipoxygenase pathway▪ Activated by C5a and produces leukotrienes (LTs).▪ Most LTs cause vasoconstriction, bronchospasm, and increased vascular permeability.

Factor XII▪ Causes pain, increased vascular permeability, vasodilation▪ Activates the clotting, fibrinolytic, and complement cascades.

Histamine▪ Release from basophils and mast cells can be caused by trauma, cold, immune reactions via IgE,C3a, or C5a binding

▪ Causes vasodilation and increased vascular permeability.

Nitric oxide▪ Produced by macrophages and endothelial cells.▪ Promotes vascular permeability and inhibits platelet aggregation.

COMPLEMENT▪ Protein made in the liver

▪ Generated in a cascade in response to antibodyantigen complexes or to bacterial cell wall

▪ C5a is a chemotactic which increases inflammatorycell adhesion

▪ C3b coats the bacteria to enhance phagocytosis byinflammatory cells

▪ C5b-C9 form the membrane attack complex (MAC)that targets the cell membrane to causes lysis.

Image: Wikimedia Commons – Author: The Immune System.pdf

HEALING MECHANISMSRegeneration

▪ Renewal of lost tissue▪ Requires the basement membrane to remain intact

Fibrosis▪ Begins with inflammation, liquefaction, and clearing of dead cells.▪ Granulation tissue is then formed and proliferation of new capillaries occurs.▪ Fibroblasts enter the area and generate collagen.▪ Scar tissue is the result and is less vascular than the surrounding tissue.

EDEMAExudate

▪ High protein content, often contains inflammatory cells▪ Serous – no inflammatory cells▪ Fibrinous – large amount of fibrin due to the activation of coagulation cascade▪ Purulent – large amount of cellular debris from inflammation▪ Suppurative – purulent exudate with significant liquefaction necrosis (i.e. pus)

Transudate▪ Low protein content, no associated with inflammation

▪ Seen in ascites, pleural effusion, lymphatic obstruction

HEMOSTASIS▪ Vasoconstriction to restrict blood loss as platelet plug is being formed.

▪ Platelets adhere to collagen via von Willebrand factor (vWF).

Coagulation Cascade▪ Intrinsic pathway

▪ Vessel endothelium ruptures and exposes underlying tissues.▪ Factors XII, XI, IX, VIII

▪ Extrinsic pathway▪ Damage to tissue cells causes release of tissue thromboplastin/tissue factor.▪ Factor VII

▪ Prothrombin activator converts prothrombin to thrombin which is used to convertfibrinogen to fibrin.

▪ Vitamin K is required for the synthesis of factors II, VII, IX, and X.

Image: Wikimedia Commons – Author: Jng46


WOUND HEALING▪ Hemostasis

▪ Inflammation▪ Leukocytes remove debris and bacteria▪ Fibroblasts migrate into the area

▪ Proliferation▪ New blood vessels form and structural proteins are deposited.▪ Granulation tissue forms, new epithelium grows, and the wound begins to contract.

▪ Remodeling▪ Collagen organizes

TYPES OF WOUND HEALINGPrimary intention

▪ Minimal damage, wound edges are close together▪ Results in minimal scarring

Secondary intention▪ More granulation tissue needed for wound healing▪ Results in a larger scar and increases the risk of infection

Tertiary intention▪ Severe and infected wounds▪ Debridement and cleaning is often required

INFECTIOUS DISEASE

INFECTIOUS DISEASEViral attachment is also called adsorption.

▪ Requires specific receptors or lectin (glycoprotein-to-glycoprotein) interactions

Syncytial bridges▪ Some enveloped viruses spread using these bridges between cell

Virulence = invasiveness

VIRAL REPLICATION1. Attachment

2. Entry

3. Viral particles break apart before replicating

4. DNA viruses migrate to the nucleus and integrate with the host’s genome.

5. New viral particles assembled

6. Host cell typically dies and releases viral particles

NEOPLASMS▪ Types

▪ Genes involved in cancer

▪ TNM staging

▪ Mutations


NEOPLASIA▪ Benign

▪ do not invade tissue or metastasize▪ well-differentiated and slow growing

▪ Premalignant▪ Carcinoma in situ

▪ Dysplastic or neoplastic cells but no breach of the basement membrane

▪ Malignant ‘-oma’▪ Can look ulcerated, invade tissue, and metastasize; less well differentiated, fast growing

▪ Sarcoma → mesenchymal (connective) tissue▪ Carcinoma → epithelial tissue▪ Adenocarcinoma → glandular tissue▪ Squamous cell carcinoma → stratified squamous epithelium

Protooncogenes▪ Code for receptors or related proteins normally involved in signal transduction▪ Ex: Ras protooncogene – causes cell growth independent of growth factors when mutated

Tumor suppressor genes▪ Normally determines when cells divide and undergo apoptosis.▪ Ex: p27 TSG – when mutated it continues cell division despite DNA damage

Telomerase▪ Causes the tips of chromosomes to lengthen with cell division rather than shrink▪ Contributes to the immortalization of cancer cells.

TNM STAGING SYSTEM▪ Stage 1

▪ T1-2 (mild to moderate)▪ N0 (no nodal involvement)▪ M0 (no metastasis)

▪ Stage 2▪ T3 (severe)▪ N0▪ M0

▪ Stage 3▪ T3▪ N1 (nodes involved)

▪ Alpha fetoprotein (AFP) and human chorionic gonadotropin (hCG):▪ highly correlated with the presence of testicular cancer.

▪ Prostate-specific antigen (PSA):▪ Used in early detection and monitoring patients with prostate cancer.

▪ CA-125:▪ Used to assess the progression of ovarian cancer

▪ Carcinoembryonic antigen (CEA):▪ used to monitor colorectal cancers

▪ CA19-9▪ used to monitor pancreatic cancer

MUTATIONSPoint mutation

▪ Can result in an altered gene splicing, premature protein synthesis termination, andnoncoding sequences.

▪ Sickle cell anemia is an example of this type of mutation.

Deletion or insertion▪ Results in a frame shift or a loss of a portion of a chromosome

Trinucleotide repeats▪ Huntington’s disease (CAG repeats in chromosome 4)

PATHOLOGY


PATHOLOGY▪ Pigmentation Changes

▪ Acute & Inflammatory

▪ Chronic & Inflammatory

▪ Blistering diseases

▪ Genetic diseases

▪ Benign & pre-malignant lesions

▪ Malignant neoplasms

▪ Infectious diseases

PIGMENTATION CHANGES

Nevocellular nevus▪ Circumscribed and hyperpigmented▪ Macules, papules, or nodules

Vitiligo▪ Autoimmune condition involving the destruction of melanocytes.▪ Patchy areas of depigmented skin which appears chalk white under Wood’s light▪ More common if pernicious anemia, thyroiditis, type 1 diabetes mellitus, or autoimmunehypoadrenocorticism is present.

ACUTE & INFLAMMATORYAtopic dermatitis

▪ Associated with allergic disorders such as asthma and hay fever.▪ Onset is common in infants; red, crusted, weeping lesions

Contact dermatitis▪ Secondary to contact with an irritant which results in local skin inflammation.

Erythemamultiforme▪ Inflammatory eruption of the skin that occurs suddenly and lasts for 2-4 weeks but can reocurr seasonally▪ Lesions are symmetric, erythematous, edematous and bullous in nature.▪ Found on the skin and mucous membranes▪ Frequently accompanied by arthralgia, malaise, and fever.

Urticaria▪ Flattened, fluid-filled vesicles with extreme pruritis▪ Almost always a result of an allergic, generally type I hypersensitivity reaction.▪ Chronic or acute and can occur anywhere on the body

CHRONIC & INFLAMMATORYAcne rosacea

▪ Idiopathic inflammatory condition mainly affecting the facial skin.▪ Most commonly seen in middle-aged adults; female:male 3:1▪ Erythema, telangiectasia, papules or pustules on the face, facial flushing, and rhinophyma .▪ Associated with sun damage, stress, immune abnormalities, food allergies, and hypochlorhydria.▪ Alcohol, vasodilators and stress can exacerbate.

Lichen planus▪ Recurrent inflammatory condition affecting thin skin that is easily torn (resulting in pain and irritation)▪ Most commonly affects the vulva and uncircumsized penis but can affect the oral cavity and skin.▪ Pruritic, polygonal-shaped, pink/purple papules

Psoriasis▪ Chronic, inflammatory autoimmune disease▪ Erythematous plaques with a silvery scaling, positive Auspitz sign▪ Most commonly on extensor surfaces of elbows and knees and usually doesn’t itch.▪ Thickening, pitting, and destruction of nails is common.▪ At risk for psoriatic arthritis (15%), uveitis

BLISTERING DISEASESEpidermolysis bullosa

▪ Rare disorder due to a mutation of the keratin gene resulting in a lack of connection between theepidermis and dermis.

▪ Extremely fragile skin and recurrent blisters.

Bullous pemphigoid▪ Chronic, benign autoimmune bullous condition that primarily affects the elderly.

▪ Primarily affects areas of friction (axilla, groin, lower abdomen,medial thighs, and forearms)▪ Immunoglobulins directly against the basement membrane zone of the epidermis

▪ Type XVII collagen of hemidesmosomes▪ Tense bullae, negative Nikolsky’s sign, extremities initially especially flexural folds, can be associatedwith pruritis, annular dusky erythematous edematous lesions.

▪ Number of intact blisters outnumber erosions.

Pemphigus vulgaris▪ Autoimmune attack on desmoglein 1 and 3 that affects keratinocyte adhesion.▪ Most commonly seen in the elderly and in people of Jewish ethnicity.▪ Painful intraepidermal flaccid bullae starting in the mouth then involving extensive areas of skin; bullaerupture easily leaving painful erosion; positive Nikolsky’s sign

GENETIC CONDITIONSAlbinism

▪ Autosomal recessive disorder of melanin synthesis.▪ Ocular albinism is X-linked and seen mainly in male.

Ehlers-Danlos syndrome (EDS)▪ A group of genetic disorders involving collagen synthesis.▪ Autosomal and recessive forms exist.

▪ Classic type 1 EDS: defect in type V collagen synthesis resulting in severe skin laxity.▪ Type 2: milder disease▪ Type 3: results in more joint laxity and hypermobility▪ Type 4: autosomal dominant; involves type III collagen; associated with a higher risk ofdeveloping an aortic aneurysm


BENIGN & PRE-MALIGNANTLESIONSActinic keratosis

▪ Sharply delineated patch or plaque on sun damaged skin that can evolve into squamous cellcarcinoma.

▪ Commonly found on the backs of hands or the face.

Dysplastic nevi▪ Larger than benign moles, irregular or indistinct borders, multi-coloured, and lack symmetry.▪ Can progress to malignant melanoma.

Seborrheic keratosis▪ Common benign neoplasm found in older populations.▪ Lesions appear in a scattered manner on the head, trunk, and extremities and are sharplydelineated papules that have a distinct ‘pasted on appearance’

▪ Initially a tiny non-pigmented papules that develops into a larger (1-6 cm diameter), greasy,darkly pigmented plaques with a bumpy surface.

MALIGNANT NEOPLASMSBasal cell carcinoma

▪ Most common skin tumor.▪ Well-circumscribed pearly papule on sun exposed skin which is locally aggressive but rarelymetastasizes.

Squamous cell carcinoma▪ Common skin tumor that is locally invasive but rarely results in metastasis.▪ Scaling, indurated, ulcerated nodule. Often initially presents as a actinic keratosis.▪ Most commonly associated with excessive sun exposure but can occur due to chemical carcinogen,radiation, or X-ray exposure.

Melanoma▪ Associated with excessive sun exposure and most common in fair-skinned people.▪ Radial growth initially and does not metastasize.▪ Vertical growth occurs later and may metastasis worsening the prognosis.

INFECTIOUS DISEASES

Acne vulgaris▪ Inflammatory condition related to plugged sebaceous glands and Propionibacterium acnesinfection.

▪ Open comedones and closed comedones, inflammatory pustules, nodules, cysts, or papules▪ Face, upper trunk, upper arms.

Candidiasis▪ Candida albicans▪ Thrush (white patches on an erythematous base that can be scraped off), vaginal candidiasis,chronic mucocutaneous candidiasis

Cellulitis▪ Pyogenic disease localized in the skin.▪ Swelling, red hot skin (possible peau d’orange appearance), fever or chills, lymphangitiscausing red streaks, regional lymphadenopathy, hypotension, tachycardia, leukocytosis, andheadache.

Erysipelas▪ Pyogenic disease that ismore superficial than cellulitis with lymphangitis.▪ Lesion (vesicles or bullae) is shiny, swollen, red, tender, and has well-defined edges.

Erythema nodosum▪ Inflammation of the deep dermis and subcutaneous fat tissue with tender red nodules.▪ Pretibial region or on the arms▪ Most commonly caused by inflammation due to URI caused by strep.

Folliculitis▪ Inflammation of hair follicles generally caused by infection by Staphylococcus aureus▪ Tender pustule(s) around a hair follicles, chronic recurrences.

Impetigo▪ Skin infection caused by Staphylococcus aureus that is highly contagious▪ Most often affects the perioral or the chin▪ Vesicles form a honey-coloured crust

▪ Begins as an erythematous macule▪ Spread by direct contact

Methicillin resistant Staphyloccocus aureus (MRSA)▪ Highly virulent and can spread to organs and the blood.▪ It can secrete the toxin that causes toxic shock syndrome and is known to cause necrotizingdisease of the skin, lungs, and other tissue.

Molluscum contagiosum▪ Caused by Molluscipox virus (enveloped DNA virus)▪ Commonly seen in children▪ Incubates for 2-8 weeks and causes painless, pearly nodules with central umbilication on theface and body in children and genitalia in adults.

▪ A cheesy substance may be expressed.

Tinea (ringworm)▪ Dermatophyte which only infects superficial keratinized structures found in stratum corneum

▪ Trichophyton and Malassezia

▪ Form annular itchy plaques with an erythematous scaly edge▪ Prefers warm and moist areas and is characterized by pruritic papules, broken hair, andthickened, broken nails.

▪ To diagnose a 10% KOH solution on a skin scraping or a Wood’s lamp is used.


Varicella zoster virus (VZV)▪ A DNA enveloped herpes virus that causes primary chickenpox disease and shingles▪ Chickenpox

▪ Incubates for 14-21 days; pruritc papulovesicular rash occurs all over the body▪ Papules turn into vesicles and pustules which eventually crust over▪ Mild in children and can be severe in adults causing encephalitis▪ Reye’s syndrome is a severe complication in children who are given aspirin.

▪ Herpes zoster▪ Shingles is a reactivation of the latent virus.▪ Painful vesicles along a dermatome.▪ Nerve pain can be debilitating and can persist after the vesicles disappear (postherpetic neuralgia)

▪ VZV infects the mucosal membranes of the URT first then spreads through the blood to the skin wherethe rash erupts.

▪ Remains latent in the dorsal root ganglia.

Verrucae▪ Raised skin lesions due to an underlying infection with human papillomavirus (HPV)▪ Condyloma acuminatum occur on the genitalia - cauliflower-like lesions▪ Some cause plantar warts and others are carcinogenic.

Wound infection/needle stick▪ Hepatitis, HIV, and other viruses are of greatest concern for transmission.

KEY POINTS▪ Layers of the skin and their components

▪ Cofactors needed for reactions

▪ Action potential

▪ Chemical mediators

▪ Cellular injury and wound healing

▪ Differentiating similar pathologies▪ Bullous pemphigoid vs pemphigus vulgaris

PRACTICE QUESTIONS1. What cytokine is involved in raising body temperature during a fever?a. IL-4b. IL-10c. IL-1d. IFN-beta

ANSWERc. IL-1

▪ The endogenous pyrogens include IL-1, IL-6, TNF which are released from WBCs,injured tissue cells, or macrophages during an infection or another stimuluscausing a fever.

▪ IL-4 promotes growth and differentiation of B-cells and is involved in switching Bcells from IgG to IgE. It is involved in the activation of eosinophils and mast cells.

▪ IL-10 inhibits the production of IL-2 and TNF by helper T-cells to favour thehumoral immune response.

▪ IFN-beta is produced by fibroblasts and has antiviral activity and can increase theproduction of other cytokines.

65-year-old woman presents with a non-healing ulcer on her nose. It is tan in colour

and slightly raised. She states she does spend a lot of time outside in her garden and

often forgets to apply sunscreen.

2. What is the most common progression of this lesion?a. Basal cell carcinomab. Seborrheic keratosisc. melanomad. Squamous cell carcinoma

PRACTICE QUESTIONSd. squamous cell carcinoma

▪ Squamous cell carcinoma are scaling, indurated, ulcerated nodule. Often initiallypresents as a actinic keratosis.

▪ Basal cell carcinoma is a well-circumscribed pearly papule on sun exposed skinwhich is locally aggressive but rarely metastasizes.

▪ The lesions of seborrheic keratosis are sharply delineated papules that appearpasted on and occur on the head, trunk, and extremities.

▪ Melanoma is associated with sun exposure, The majority of melanomas areblack or brown, but they can also be skin-colored, pink, red, purple, blue orwhite.

ANSWER


IN THE NEXT SECTION…

▪Section 8: Musculoskeletal System

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Lecture N7 Integumentary System