Anatomy of skin & inflammation

Dr.K.Priyatham

Introduction

• Survival of all living organisms requires that they should eliminate foreign invaders , such as infectious pathogens & damaged tissues .

• These functions are mediated by complex host immune response called as an Inflammation.

• Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process.

• Hence without inflammation, wounds and infections would never heal.

Inflammation

• Definition –

The word inflammation is derived from

Latin word inflammare, which means “to set

on fire.”

Inflammation

• It is a complex reaction to injurious agents such as microbes & damaged, usually necrotic, cells that consists of vascular responses, migration & activation of leukocytes & systemic reactions.

SIGNS OF INFLAMMATION• RUBOR- REDNESS DUE TO INCREASED BLOOD BLOW AND VASODILATION• CALOR- OR HEAT DUE TO INCREASE BLOOD FLOW TO THE PERIPHERY• TUMOR- SWELLING FROM INFLAMMATORY EDEMA• DOLOR-PAIN FROM SWELLING AND PRESENCE OF INFLAMMATORY

MEDIATORS• FUNCTIO LAESA-LOSS OF FUNCTION DUE

TO MAIN AND STRUCTURAL NECROSIS

2nd Yr Pathology 2010

Inflammation

The basis of the five cardinal signs

• Increased blood flow due to vascular dilatation gives redness and heat.

• Increased vascular permeability gives oedema causing tissue swelling.

• Certain chemical mediators stimulate sensory nerve endings giving pain. Nerves also stimulated by stretching from oedema.

• Pain and swelling result in loss of function.

Types of inflammation 1. Acute inflammation – It is the rapid response to the injury or microbes or other

foreign substances that is designed to deliver leukocytes & plasma proteins to the site of injury .

Causes –2. Infections – Bacterial , viral , fungal or parasitic3. Trauma –Blunt or Penetrating 4. Tissue necrosis- 5. Foreign bodies – sutures 6. Immune reactions

• Outcomes of acute inflammation-1. Resolution2. Progression to chronic inflammion.3. Scarring or fibrosis

2. Chronic inflammation –• It is inflammation of prolonged duration in which

active inflammation, tissue injury & healing proceed simultaneously .

• Immunologists define as period when macrophages predominate

• Clinicians define as recurrent inflammation prior to completion of repair or resolution

• Causes –1. Persistent infection 2. Immune mediated inflammatory diseases3. Prolonged exposure to potentially toxic agents

Ulcers Resolution Fistulas Granulomatous diseases Fibrotic diseases (Scaring) combinations of the above

Outcome of chronic inflammation

Differences between Acute & Chronic Inflammation

Acute inflammation Chronic inflammation

Definition It is the rapid response to the injury or microbes or other foreign substances that is designed to deliver leukocytes & plasma proteins to the site of injury .

It is inflammation of prolonged duration in which active inflammation, tissue injury & healing proceed simultaneously .

Onset Rapid Insidious

Duration Short ( Few minutes to days )

Long (Days to years )

Acute inflammation Chronic inflammation

Specificity Non- specific Specific, where immune response is activated

Cells involved Neutrophils Lymphocytes , plasma cells , macrophages , fibroblasts

Vascular changes

Active vasodilation ,Increased vascular permeabilty

New vessels formation(Neoangiogenesis )

Fluid exudation & edema

Present Absent

Cardinal signs Present Absent

Acute inflammation Chronic inflammation

Tissue necrosis Absent Ongoing

Systemic manifestations

High grade fever Low grade fever, weight loss , anemia

Pathophysiology of inflammation

Inflammed (Vasodilation in capillary bed)

NormalArteriole Venule

Capillary bed

Leukocyte Transmigration , Chemotaxis & Phagocytosis

Resolution of Inflammation

Pathophysiology of inflammation

Outcomes of Acute Inflammation • Resolution of tissue structure and function with elimination of

stimulus • Tissue destruction and persistent inflammation

– Abscess • pus-filled cavity (neutrophils, monocytes and liquefied cellular debris) • walled off by fibrous tissue and inaccessible to circulation • tissue destruction caused by lysosomal and other degradative enzymes

– Ulcer • loss of epithelial surface • acute inflammation in epithelial surfaces

– Fistula • abnormal communication between organs or an organ and a surface

– Scar • Causes distortion of structure and sometimes altered function

• Chronic inflammation – Marked by replacement of neutrophils and monocytes with lymphocytes,

plasma cells and macrophages – Accompanied by proliferation of fibroblasts and new vessels with

scarring

Inflammatory cells

1. Blood leukocytes – Neutrophils , Macrophages, Lymphocytes.2. Plasma cells 3. Connective tissue cells – Fibroblasts, Mast cells.4. Cells of vascular walls .

Inflammatory mediators • Definition – Chemical substances that trigger certain

processes in an inflammatory reaction.

Cell derived Plasma derived

Histamine Kinin system mediators

Serotonin C- reactive protein

Neutrophilic proteases Complement system mediators

Interleukins( IL-1 . TNF- α )

Chemokines

Arachidonic acid (PG, LT)

PAF

Repair Process• Removal of Debris

– begins early and initiated by liquefaction and removal of dead cells and other debris

• Formation of Granulation Tissues – connective tissue consisting of capillaries and

fibroblasts that fills the tissue defect created by removal of debris

• Scarring – fibroblasts produce collagen until granulation tissue

becomes less vascular and less cellular – progessive contraction of the wound occurs, resulting

in deformity of original structure

Factors that Impede Repair

• Retention of debris or foreign body • Impaired circulation • Persistent infection • Metabolic disorders

– diabetes• Dietary deficiency

– ascorbic acid – protein

Healing and granulation • Fibroplasia is a response to

– Damaged connective tissue– Parenchymal damage exceeds regenerative capacity

• Hyperplasia of connective tissue • Neovascularization• Granulation

– coordinated proliferation of fibroblasts with a rich bed of capillaries

– intensely hyperemic with a roughened or granular, glistening surface

– healthy granulation tissue resists secondary infections

Healing by First Intention• Clean, surgical incision or other clean narrow cut• Focal disruption of epithelial basement membrane

with little cell damage• Regeneration dominates fibrosis• Scabbing with fibrin-clotted blood• Neutrophils migrate to edges• Epidermis becomes mitotic and deposits ECM• Macrophages replace neutrophils• Vascularization and collagen deposition fills gap• Contraction of collagen minimizes epidermal

regeneration

Healing by Second Intention• Larger area of tissue injury such as abcess, ulcer,

infarction that destroys ECM• Large clot or scab with fibrin and fibronectin fills gap• Larger volume of necrotic debris must be removed

by more neutrophils and macrophages– Opportunity for collateral damage by phagocytes

• Scar tissue formed from vascular cells, fibroblasts, and myofibroblasts

• Contraction of myofibroblasts distorts tissue• More prone to infection

When healing goes wrong

Keloid scar

SKIN - Basic structure

introduction

• Skin is the largest organ of the human body• Accounts for 16-20% of body weight…it weighs twice as much

as your brain• For the average adult human, the skin has a surface area of

between 1.5-2.0 sq.mtrs• The skin is composed of two basic layers (regions)..

– Epidermis – outermost layer– Dermis –underlying connective tissue

• Subcutaneous fat (Hypodermis),inspite of its close anatomic relationship and tendency to respond jointly to pathologic processes,is not a part of skin basic structure

Functions• The skin is an organ of protection. The primary function of the

skin is to act as a barrier. The skin provides protection from: mechanical impacts and pressure, variations in temperature, micro-organisms, radiation and chemicals.

• The skin is an organ of regulation. The skin regulates several aspects of physiology, including: body temperature via sweat and hair, and changes in peripheral circulation and fluid balance via sweat. It also acts as a reservoir for the synthesis of Vitamin D.

• The skin is an organ of sensation. The skin contains an extensive network of nerve cells that detect and relay changes in the environment. There are separate receptors for heat, cold, touch, and pain.

EPIDERMIS

• Primarily made up of keratinized stratified squamous

epithelium(keratinocytes)

• Gives strength to the skin.

• Varies in thickness from thick skin to thin skin

• Eyelids- 0.04 mm,Palms- 1.6 mm,average 0.1 mm

• It does not have any vascularization, so it relies on the connective

tissues deep to it.

• Also contain melanocytes, merkel’s cells and Langerhans cell

Layers of epidermis • Stratum basale (the deepest layer)• Stratum spinosum• Stratum granulosum• Stratum lucidum • Stratum corneum (most superficial layer of epidermis)

Stratum Basale

• The stratum germinativum (or basal layer, stratum basale)

Consists of single layer of basophilic columnar or cuboidal

cells.

• Along with S. spinosum, it is a component of Malpighian layer

• Cells are bound to each other by desmosomes and to basal

lamina by hemidesmosomes.

• All cells contain intermediate keratin filaments, number of

which increases as cells progress upward.

Stratum Spinosum• Also contain the dividing cells as in basale.• Cells contain bundles of intermediate filament

(tonofilaments) projecting into the processses of cells which give attachment to the desmosomes, so giving spined appearance.

• Tonofilaments provide resistant to the abrasion so this layer is thicker in the areas prone to abrasion (thick skin) .

• Keratinization begins in the stratum spinosum.

Stratum granulosum

• Consists of polygonal cells , cytoplasm of which is filled with

the basophilic granule , keratohyaline granules. It is rich in

phosphorylated histidine and cystine.

• Cells contain, lamellated bodies, made up of lipid. It fuses

with the cell membrane and it come out of cells and function

as a intercellular cement or sealing agent.

• This sealing effect is first evolutionary adaptation to

terrestrial life

Stratum Lucidum

• More prominent in thick skin .Cellular organells and

nuclei are not prominent.

• It is composed of clear non-nucleated cells.

• In the palms and soles, the stratum

lucidum is present. The tan colored protein blocks the

underlying melanocytes from view

Stratum corneum

• The main difference between thick skin and thin skin relates to the thickness of the Stratum corneum.

• These are the dead cells, flaking off. The cells lose their nucleus and fuse to form squamous sheets, which are eventually shed from the surface (desquamation).

• The mean turnover or renewal time of epidermis is 39 days(13+12+14) i.e.,time for a cell to move from the stratum basale to the distal edge of the stratum corneum and shed

• 13 days for proliferative compartment( lower two rows),12 days for differentiated compartment,14 days for cornified layer

Dermis • It is connective tissue that support the epidermis and attaches the epidermis

to the hypodermis.• Dermis is 15-40 times thicker than the epidermis• Its surface consists of many ridges (dermal papillae) which interdigitate with

epidermal ridges. • The dermis is also the area where all the glands of the body are located.• Has 2 layers/compartments1. A thin zone immediately beneath the epidermis (the papillary dermis) and

around adnexa ( the periadnexal dermis).The combination of papillary and periadnexal dermis is called Adventitial dermis

2. A thick zone of Reticular dermis that extends from the base of the papillary dermis to the surface of the subcutaneous fat

Papillary dermis

Papillary layer –The papillary dermis is the uppermost layer of the dermis,composed of thin haphazardly arranged collagen bundles,delicate branching elastic fibers,numerous fibrocytes,abundant ground substance.A highly developed microcirculation composed of arterioles,capillaries and venules

Its superior surface is uneven (fingerlike projections) which forms the characteristic fingerprint of the finger. This layer provides the epidermis with nutrients. Pain and touch receptors are found here

• Together,the papillary dermis and epidermis form a morphologic and functional unit whose intimacy is reflected in their alteration jointly in various inflammatory processes

• A similar interrelationship exists b/w periadnexal layer and its adjacent epithelium

Reticular dermis

• Dense irregular Connective Tissue

• Has thick bundles of Collagen and coarse Elastic fibers.Proportionally,

there are fewer fibrocytes and blood vessels and less ground substance

compared to papillary dermis

• Arrangement of bundle in the direction of mechanical force give rise to

the cleavage lines of Langer.

• Strongest layer of the Dermis.Gives the area strength.Contains

sweat,sebaceous glands and pressure receptors

• Leather is made of this layer.

HYPODERMIS•Consists of loose connective tissue which helps in sliding the skin over the deep structure.•Consists of layer of fat according to the nutritional status of the person.•Also called as superficial fascia or panniculus adiposus

VESSELS IN SKINArteries form the 2 plexuses. One at the junction of papillary and reticular layer( sub- papillary plexus) and another at junction of dermis and hypodermis (cutaneous plexus).Veins form the three plexuses – 2 in same position as for arterial and another in the middle of the dermis

Cutaneous Glands1. Sebaceous (oil) glands-Sebaceous glands are microscopic glands in

the skin which secrete an oily matter, called sebum, in the hair follicles to lubricate the skin and hair. In humans, they are found in greatest abundance on the face and scalp, though they are distributed throughout all skin sites except the palms and soles. An infection causes acne

2. Sweat (sudoriferous) glands - Sweat glands are exocrine glands, found in the skin , that are used for body temperature regulation.

a) Eccrine glands -Eccrine glands (or merocrine glands) are found at virtually all sites on the human body. They produce clear liquid (perspiration), consisting of water, salts, and urea.

b) Apocrine glands- Apocrine glands are found in axillary and genital areas, secrete a milky protein and fat substance. This mixture is an excellent source of nutrients for bacteria which produce body odour.

hair• Follicle- A hair follicle is a part of the skin that grows hair by packing old cells together.

• Root• Shaft• Hair bulb

Arrector pili -Arrectores pilorum (singular Arrector pili) are tiny muscle fibers

attached to each hair follicle, which contract to make the hairs stand on end,

causing goose bumps. Arrectores pilorum are smooth muscle, not skeletal

muscle, which explains why humans cannot voluntarily give themselves goose

bumps.

nails• Fingernails and toenails are made of a tough protein called keratin. Along

with hair and teeth they are an appendage of the skin.

• Free edge- The part of the nail that extends past the finger, beyond the nail plate. There should always be a free edge present to prevent infections.

• Nail folds (cuticle)- A fold of hard skin overlapping the base and sides of a fingernail or toenail

• Nail Matrix- This is the only living part of the nail. It is situated behind and underneath the Nail Fold and produces protein keratin which makes up the Nail Plate.

PRIMARY SKIN LESIONS

PRIMARY SKIN LESIONS MACULE

• MACULE IS A CIRCUMSCRIBED FLAT AREA LESS THAN 2 CMS OF DISCOLORATION WITHOUT ELEVATION OR DEPRESSION OF SURFACE RELATIVE TO SURROUNDING SKIN

MACULE

PAPULE

• PAPULE IS A CIRCUMSCRIBED, ELEVATED, SOLID LESION LESS THAN 0.5 CMS IN DIAMETER, SUCH AS THE LESIONS OF LICHEN PLANUS AND NONPUSTULAR ACNE

PAPULE

PATCH AND BULLA• PATCH IS A CIRCUMSCRIBED AREA OF

DISCOLORATION, GREATER THAN 2CMS WHICH IS NEITHER ELEVATED OR DEPRESSED RELATIVE TO THE SURROUNDING SKIN

• BULLAE ARE RAISED, CIRCUMSCRIBED LESION GREATER THAN 0.5 CM THAT CONTAIN SEROUS FLUID

PATCH and BULLAE

TUMOR and VESICLE• TUMOR – is a solid, firm lesion about 2

cms in diameter that can be above, level with or beneath the skin surface. It is also called a mass.

• VESICLE – is a small , superficial elevation of the skin, less than 0.5 cm, that contains serous fluid.

TUMOR and VESICLE

PLAQUE AND PUSTULE• PLAQUE IS A WELL-CIRCUMCRIBED,

ELEVATED, SUPERFICIAL, SOLID LESION, GREATER THAN 1 CM IN DIAMETER

• PUSTULE IS A SMALL (1CM IN DIAMETER) CIRCUMSCRIBED SUPERFICIAL ELEVATION OF THE SKIN THAT IS FILLED WITH PURULENT MATERIAL

PLAQUE and PUSTULE

WHEAL IS TRANSIENT, CIRCUMSCRIBED, ELEVATED PAPULES

OFTEN WITH ERYTHEMATOUS

BORDERS AND PALE CENTERS

Thank you