Pathology

Characterize the changes in a keratinocyte from its inception in the basal lamina to its arrival on the outer surface of the skin.

The journey of a keratinocyte is one of production, migration, and differentiation across the layers of the epidermis

objective 1: in depth of keratinocytes step 1

Inception (Stratum Germinativum/ or Basale): The process begins in the deepest epidermal layer, the stratum germinativum. Here, columnar basal cells undergo mitosis to produce new keratinocytes. At this stage, the cells are cuboidal to low columnar in shape.

objective 1 keratinocytes step 2

 Migration and Differentiation (Stratum Spinosum & Granulosum):As new cells are produced, they are pushed toward the skin's surface.

In the stratum spinosum, the keratinocytes become multisided and develop a spiny appearance where their borders connect.

    In the stratum granulosum, the cells become the most differentiated of the living skin, growing progressively flatter. They lose their cytoplasm and nuclear structures while continuing to synthesize keratin. They also secrete lamellar bodies, which make the skin water-impermeable.

objective step 3

Transition (Stratum Lucidum): In thick skin areas like the palms and soles, keratinocytes pass through this thin, transparent layer of transitional cells.

step 4

 Arrival (Stratum Corneum):The journey ends at the most superficial layer, the stratum corneum. By this point, the keratinocytes are dead, keratinized, flattened, and elongated. They form a durable, protective barrier that is continuously shed and replaced by new cells from below

Objective 2: Describe the following skin appendages and their functions: sebaceous gland, eccrine gland, apocrine gland, nails, and hair.

Skin appendages are specialized structures formed by the epidermis.

 objective 2:Sebaceous Glands

These glands produce an oily secretion called sebum.

Sweat Glands:

These glands produce watery secretions. Your sources mention two types:

    ◦ Apocrine Glands: These are found in limited locations, specifically the axillae (armpits) and anogenital areas.

    ◦ Eccrine Glands: This type is mentioned in the learning objectives but is not described further in the provided text.

• Hair and Nails: Both hair and nails are mentioned as skin appendages formed from the epidermis. Hair follicles are densely distributed on the scalp, axillae, and genitalia.

◦ Apocrine Glands:

These are found in limited locations, specifically the axillae (armpits) and anogenital areas.

◦ Eccrine Glands

This type is mentioned in the learning objectives but is not described further in the provided text.

Hair and Nails:

 Both hair and nails are mentioned as skin appendages formed from the epidermis. Hair follicles are densely distributed on the scalp, axillae, and genitalia.

Objective 3: Characterize the skin in terms of sensory and immune functions.

 Sensory Function: The skin is a key part of the sensory system. Specialized Merkel cells, located in the epidermis, are responsible for providing sensory information.

• Immune Function: The skin's immune role is linked to Langerhans cells, which are also found in the epidermis. These cells connect the epidermis to the broader immune system, acting as a first line of defense.

 Sensory Function:

The skin is a key part of the sensory system. Specialized Merkel cells, located in the epidermis, are responsible for providing sensory information.

Immune Function:

The skin's immune role is linked to Langerhans cells, which are also found in the epidermis. These cells connect the epidermis to the broader immune system, acting as a first line of defense.

Detailed Structure and Function of the Skin

The skin, also known as the integumentum, is a versatile organ that accounts for about 16% of the body's weight.

layers of the skin

The skin consists of three primary layers:

1. Epidermis (Outer Layer):

2. Dermis (Inner Layer):

3. Subcutaneous Layer (Hypodermis):

epidermis outer layer

    ◦ Structure: This is an avascular (lacks blood vessels) layer composed of four to five strata of keratinized epithelial cells. Its thickness varies, from about 0.5 mm on the eyelid to 1.5 mm on the sole of the foot.

    ◦ Function: As the outermost layer, the epidermis provides the skin's primary protective functions. It contains openings for sweat and sebaceous glands.

Dermis (inner layer)

    ◦ Structure: The dermis is a layer of connective tissue that contains the blood vessels and nerve fibers that supply the epidermis. It is separated from the epidermis by the basement membrane. The dermis is thickest on the back.

Subcutaneous Layer (Hypodermis):

◦ Structure: This layer is composed of loose connective and adipose (fat) tissues. It is thickest on the abdomen and buttocks.

    ◦ Function: It binds the dermis to the underlying tissues of the body.

. Key Functions of the Skin

Protection: It serves as the body's first line of defense against harmful environmental agents like microorganisms, chemicals, and sunlight. It also protects underlying muscles, bones, and organs.

• Thermoregulation: The skin plays a role in regulating body temperature.

• Interface with the Environment: It forms the major interface between the internal organs and the external world.

• Indicator of Systemic Disease: Skin disorders can be manifestations of internal diseases, such as the bronze skin of Addison disease or the jaundice seen with liver disease

Pathophysiology Spotlight: Pressure Ulcers

Immobility is the single factor most likely to put an individual at risk of altered skin integrity. This leads to a common and serious skin disorder known as pressure ulcers

Aetiology (Cause) of ulcers

• Mechanism

Pressure ulcers (also called bedsores or decubitous ulcers) are caused by prolonged pressure on the skin, which compresses blood vessels in the dermis. This compression deprives the skin tissue of blood (a condition called ischemia), leading to tissue death (necrosis). The risk is highest where skin is stretched tightly over bony prominences, such as the heels or sacrum.

 Contributing Factors: of the ulcers

◦ Healthy individuals automatically shift their weight, even while asleep, to relieve pressure. Patients on bedrest often lack the muscle mass and strength to reposition themselves.

    ◦ Patients with decreased sensation (such as from sensory neuropathy) may not feel the pain that would normally prompt them to move.

 At-Risk Body Sites

• While the soles of the feet are adapted for prolonged weight-bearing, other areas are not.

• About 95% of all pressure ulcers develop at five main sites: the sacrum, ischial tuberosity (sitting bones), greater trochanter (hip), heel, and ankle.

• In patients lying down (supine), ulcers most frequently occur on the sacrum and heels.

Risk Factors and Prevention

Primary Risk Factor: Extended immobility is the main risk factor for developing pressure ulcers.

• Other Modifiable Risks: Poor nutrition, high body mass index (BMI), and smoking can increase the risk.

• Prevention:

    ◦ The best prevention strategy is to mobilize as soon as possible.

    ◦ Other key preventive measures include frequent changes of position, meticulous skin care, early risk assessment, and ensuring adequate nutrition and hydration.

Functions of the Skin

• Prevents body fluids from leaving the body

• Protects body from potentially damaging environmental agents

• Serves as an area for heat exchange (temperature regulation)

• Provides protection against invading microorganisms

Primary Skin Lesions Flat Lesions

flat lesions

• Macule:

• Patch:

Raised Solid Lesions

• Papule:

  Nodule (not shown but important):

  Wheal:

  Fluid-Filled Lesions

  • Vesicle:

  • Bulla:

  • Pustule:

Macule:

• Circumscribed, flat, non-palpable, discolored spot

• Sharp borders

• Size: < 1 cm

• Examples: freckles, flat moles, petechiae

Patch:

• Flat, non-palpable, irregular shape

• Size: > 1 cm

• Example: vitiligo

Papule:

• Raised, solid, without fluid

• Sharp borders

• Size: < 1 cm

• Examples: elevated mole, wart

Nodule (not shown but important):

• Solid, raised lesion, deeper than papule

• Size: > 1 cm

Wheal:

• Raised, irregular-shaped area of edema (localized swelling)

• Transient (comes and goes)

• Examples: insect bite, allergic reaction, hives

Vesicle:

• Small, fluid-filled blister

• Size: < 5 mm (0.5 cm)

• Examples: herpes simplex, chickenpox

Bulla:

• Larger fluid-filled blister

• Size: > 5 mm

• Examples: burns, blister from friction

Pustule:

• Elevated, pus-filled lesion

• Example: acne

Secondary Skin Lesions

1. Scar

2. Keloid

3. Scale

4. Crust

5. Fissure

6. Erosion

7. Ulcer

8. Lichenification

Scar

• Fibrous tissue replaces normal skin after injury.

Keloid

• Overgrowth of scar tissue.

• Extends beyond original wound boundaries.

Scale

• Thin flakes of keratinized epithelium.

• Seen in psoriasis, lupus.

Crust

• Dried residue of serum, blood, or pus

5. Fissure

• Linear crack in skin.

• May extend into dermis.

6. Erosion

• Loss of superficial epidermis.

• Appears moist and depressed.

Ulcer

• Loss deeper than epidermis.

• Necrotic tissue, bleeding, scarring possible.

8. Lichenification

• Thickened, roughened skin.

• Due to repeated rubbing, irritation, scratching.

Bacterial Infections

• Impetigo

  • Small vesicle/pustule or large bulla (face)

  • Caused by Staph or Strep

• Ecthyma

  • Ulcerative form of impetigo (Strep, S. aureus, Pseudomonas)

  • Ritter disease: Staph scalded skin syndrome

  • Scarlet fever-like rash (true scarlet fever = Strep)

• Cellulitis

  • Deep infection into dermis & subcutaneous tissue

• Impetigo

• Small vesicle/pustule or large bulla (face)

• Caused by Staph or Strep

• Ecthyma

• Ulcerative form of impetigo (Strep, S. aureus, Pseudomonas)

• Ritter disease:

• Staph scalded skin syndrome

• Scarlet fever-like rash (true scarlet fever = Strep)

• Cellulitis

• Deep infection into dermis & subcutaneous tissue

Viral Infections

• Human papillomavirus (HPV)

  • Causes verrucae (warts), benign papillomas

• Herpes simplex virus (HSV)

  • Type 1: Oral herpes (spread by respiratory droplets or saliva contact)

  • Type 2: Genital herpes

• Herpes zoster (Shingles)

  • Localized vesicular eruption

  • Distributed over a dermatomal segment of skin

• Human papillomavirus (HPV)

• Causes verrucae (warts), benign papillomas

• Herpes simplex virus (HSV)

• Type 1: Oral herpes (spread by respiratory droplets or saliva contact)

• Type 2: Genital herpes

• Herpes zoster (Shingles)

• Localized vesicular eruption

• Distributed over a dermatomal segment of skin

Acne Disorders

• Non-inflammatory

  • Comedones (whiteheads, blackheads)

  • Sebum plugs in sebaceous glands

• Inflammatory

  • Papules, pustules, nodules, cysts

  • Caused by sebum escaping into dermis → irritation from fatty acids

• Acne vulgaris

  • Chronic inflammatory disease of pilosebaceous unit

• Acne conglobata

  • Severe: multiple openings, large abscesses, interconnecting sinuses

  • Discharge: odoriferous, serous/mucoid/purulent

  • Associated with anemia, ↑WBC, ↑ESR, ↑neutrophils

• Non-inflammatory

• Comedones (whiteheads, blackheads)

• Sebum plugs in sebaceous glands

• Inflammatory

• Papules, pustules, nodules, cysts

• Caused by sebum escaping into dermis → irritation from fatty acids

• Acne vulgaris

• Chronic inflammatory disease of pilosebaceous unit

• Acne conglobata

• Severe: multiple openings, large abscesses, interconnecting sinuses

• Discharge: odoriferous, serous/mucoid/purulent

• Associated with anemia, ↑WBC, ↑ESR, ↑neutrophils

Inflammatory Disorders

• Rosacea

  • Chronic inflammation with vascular instability

  • Leakage of fluid & inflammatory mediators into dermis

  • May include gastrointestinal symptoms

  • Types:

    • Erythematotelangiectatic (facial flushing)

    • Papulopustular (inflammatory)

    • Phymatous (thickening, nodules)

    • Ocular (eye involvement)

• Rosacea

• Chronic inflammation with vascular instability

• Leakage of fluid & inflammatory mediators into dermis

• May include gastrointestinal symptoms

• Types:

  • Erythematotelangiectatic (facial flushing)

  • Papulopustular (inflammatory)

  • Phymatous (thickening, nodules)

  • Ocular (eye involvement)

Allergic & Hypersensitivity Disorders

• Urticaria (Hives)

  • Pale, raised, itchy papules/plaques (superficial dermis)

• Contact dermatitis

  • Allergic: Type IV hypersensitivity reaction

  • Irritant: Caused by chemical irritation

• Atopic dermatitis

  • Inflammatory, poorly defined erythema, edema, vesicles, weeping (acute stage)

• Nummular (discoid) eczema

  • Coin-shaped papulovesicular patches

• Lichenification

  • Thickened skin in chronic stage of dermatitis

• Urticaria (Hives)

• Pale, raised, itchy papules/plaques (superficial dermis)

• Contact dermatitis

• • Allergic: Type IV hypersensitivity reaction

  • Irritant: Caused by chemical irritation

• Atopic dermatitis

• Inflammatory, poorly defined erythema, edema, vesicles, weeping (acute stage)

• Nummular (discoid) eczema

• Coin-shaped papulovesicular patches

• Lichenification

• Thickened skin in chronic stage of dermatitis

Drug-Induced Skin Eruptions

• Systemic drugs → generalized skin lesions

• Topical drugs → contact dermatitis-type rashes

• Bullous skin lesions:

  • Erythema multiforme minor

  • Stevens-Johnson syndrome (SJS): <10% body surface

  • Toxic epidermal necrolysis (TEN): >30% epidermal detachment

• Systemic drugs →

• generalized skin lesions

• Topical drugs →

• contact dermatitis-type rashes

• Bullous skin lesions:

• Erythema multiforme minor

• Stevens-Johnson syndrome (SJS):

• <10% body surface

• Toxic epidermal necrolysis (TEN):

• >30% epidermal detachment

Skin Conditions in the Elderly

Normal aging changes

• ↓ Subcutaneous tissue

• Thinning of epidermal & dermal layers

• ↓ Melanocytes, Langerhans cells, Merkel cells

• ↓ & thickening of blood vessels

Common aging lesions

• Skin tags

• Keratoses (seborrheic keratosis = “stuck on” appearance)

• Actinic keratosis → precancerous

• Lentigines (liver spots, sun spots)

• Vascular lesions: telangiectasias, angiomas, venous lakes

• Skin tags

harmless growth that appear anywhere in skin

• Keratoses

• (seborrheic keratosis = “stuck on” appearance)

• Actinic keratosis →

• precancerous

• Lentigines

• (liver spots, sun spots)

• Vascular lesions:

• telangiectasias, angiomas, venous lakes

Acanthosis Nigricans (Metabolic Hyperpigmentation)

• Pigmented hyperkeratoses in skin flexures (axilla, perineal area, back of neck)

• Lesions: symmetric, verrucous, papillary

• Associated with:

  • Paraneoplastic syndrome

  • Metabolic syndrome (insulin resistance, obesity, diabetes)

pulosquamous Dermatoses

• Psoriasis

  • Chronic inflammatory disorder

  • Well-demarcated red plaques with silvery scales

  • Autoimmune (T-cell mediated)

• Pityriasis rosea

  • Self-limiting, inflammatory

  • Starts with “herald patch”, then generalized rash

• Lichen planus

  • Inflammatory, unknown cause

  • Purple, polygonal, pruritic, papules (the 4 Ps)

• Psoriasis

• Chronic inflammatory disorder

• Well-demarcated red plaques with silvery scales

• Autoimmune (T-cell mediated)

• Pityriasis rosea

• Self-limiting, inflammatory

• Starts with “herald patch”, then generalized rash

• Lichen planus

• Inflammatory, unknown cause

• Purple, polygonal, pruritic, papules (the 4 Ps)

Arthropod Infestations

• Scabies

  • Infestation with Sarcoptes scabiei mite

  • Burrows, small papules, intense itching (worse at night)

  • Common sites: finger webs, wrists, axillae, waist

• Pediculosis (Lice)

  • Infestation with Pediculus humanus capitis (head lice), P. corporis (body lice), Phthirus pubis (pubic lice)

  • Intense pruritus, visible lice/nits on hair shafts

• Scabies

• Infestation with Sarcoptes scabiei mite

• Burrows, small papules, intense itching (worse at night)

• Common sites: finger webs, wrists, axillae, waist

• Pediculosis (Lice)

• Infestation with Pediculus humanus capitis (head lice), P. corporis (body lice), Phthirus pubis (pubic lice)

• Intense pruritus, visible lice/nits on hair shafts

Pressure Injuries (Decubitus Ulcers, Bedsores)

• Caused by ischemia from unrelieved pressure

• Stages:

  • Stage I: Red, non-blanchable intact skin

  • Stage II: Partial-thickness skin loss (epidermis/dermis)

  • Stage III: Full-thickness skin loss into subcutaneous tissue

  • Stage IV: Full-thickness skin loss with exposed muscle, bone, or supporting structures

• Caused by ischemia from unrelieved pressure

• Stages1

• Caused by ischemia from unrelieved pressure

• Stages:

  • Red, non-blanchable intact skin

• • Stage II:

• Partial-thickness skin loss (epidermis/dermis)

• Stage III:

• Full-thickness skin loss into subcutaneous tissue

• Stage IV:

• Full-thickness skin loss with exposed muscle, bone, or supporting structures

Nevi & Skin Cancer

• Nevi (moles) → benign tumors of skin cells

• Malignant melanoma

  • Most dangerous skin cancer

  • ABCDE rule: Asymmetry, Border irregularity, Color variation, Diameter >6mm, Evolution

• Basal cell carcinoma

  • Most common, least aggressive

  • Nodular, pearly appearance

• Squamous cell carcinoma

  • Red, scaling, keratotic lesion

  • May ulcerate

• Nevi (moles) →

• benign tumors of skin cells

• Malignant melanoma

• Most dangerous skin cancer

• ABCDE rule: Asymmetry, Border irregularity, Color variation, Diameter >6mm, Evolution

• Basal cell carcinoma

• Most common, least aggressive

• Nodular, pearly appearance

• Squamous cell carcinoma

• Red, scaling, keratotic lesion

• May ulcerate

Skin Disorders of Infancy

• Port-wine stains (capillary malformation, vascular birthmark)

• Mongolian spots (pigmented birthmarks, common in darker skin)

• Diaper rash (irritant dermatitis)

• Hemangiomas (benign vascular tumors)

• Cradle cap (seborrheic dermatitis in infants, greasy scales)

• Prickly heat (miliaria, sweat gland obstruction → small red papules)

• Nevi (benign pigmented lesions, “birthmarks”)

• Port-wine stains

• (capillary malformation, vascular birthmark)

• Mongolian spots

• (pigmented birthmarks, common in darker skin)

• Diaper rash

• (irritant dermatitis)