Pathophysiology Case 1: Ricky Anderson LO's

Describe the role of vasodilation in the process of acute inflammation.

Vasodilation: The increased size of blood vessels causes slower blood velocity and increased blood flow to the injured site. Occurs in arterioles (blood vessels) in response to the release of histamines from the mast cells.

Describe the role of increased vascular permeability and blood flow in the process of acute inflammation.

Increased Vascular permeability and increased blood flow: blood vessels undergo structural changes to become porous from contraction of the epithelial cells - this allows for the passage of plasma proteins and white blood cells out of circulation.

Describe the role of increased blood flow in the process of acute inflammation.

leakage of fluid out of the vessels (exudation) causes edema (swelling) at the injury site. Blood in microcirculation becomes more viscous (thick). It flows more slowly and the increased blood flow and increasing concentrations of red blood cells at the site of inflammation cause locally increased erythema (redness) and warmth.

Describe the role of leukocyte emigration in the process of acute inflammation.

Leukocytes (white blood cells) adhere or stick to the inner walls of vessels and migrate through enlarged junctions between the endothelial cells lining the vessels into surrounding tissue in a process called Diapedesis.

Describe chronic inflammation

Chronic inflammation lasts 2 weeks or longer regardless of cause

At times, it can be proceeded by an unusual acute inflammatory response such as those that are complicated by:

- Bacterial contamination or foreign objects might interfere, leading to inadequate healing and prolonged inflammation

- microorganisms are insensitive to phagocytes and macrophages and prolonged inflammation

- Chronic inflammation can lead to Granuloma formation - neutrophils and macrophages are unable to destroy microorganisms (ex: in TB)

Calor

heat - increased chemical activity and increased blood flow to skin surface

Dolor

pain - due to direct injury of nerve fibers, pressure of inflammation on nerve endings and chemical irritants (bradykinin, histamine and prostaglandin)

Rubor

redness - caused by dilation of arterioles and increased blood flow

Tumor

swelling - caused by accumulation of blood and damaged tissue cells

Functio laesa

loss of function - increased pain/swelling (due to all above factors)

List external factors of Acute Inflammation

External factors: non-microbial or microbial

Non-microbial - allergens (hypersensitivity reactions), irritants and toxic compounds

Microbial - virulence factors and pathogen associated molecular patterns (PAMPs)

List internal factors of Acute Inflammation

Infection or necrosis (ex: trauma, oxygen deprivation or ischemia, nutrient deprivation, genetic or immune effects, chemical injury, foreign bodies, temperature extremes, ionizing radiation)

Epidermis

superficial or outer layer of the skin, made up of mostly keratinocytes and melanocytes

Dermis

middle layer - contains sensory receptors, sweat glands, hair follicles and blood vessels

Hypodermis

(subcutaneous layer) - lowest lying layer of connective tissue that contains macrophages, fibroblasts, fat cells, nerves, fine muscles, blood vessels, lymphatics and hair follicle roots.

what skin layer(s) are affected in psoriatic skin manifestations

both the dermis and epidermis are thickened because of keratinocyte proliferation, altered keratinocyte differentiation and expanded dermal vasculature

what skin layer(s) are affected in eczematous skin manifestations

affects epidermis only

Explain the anatomic basis for the skin as a barrier

The skins primary function is to protect the body from the environment by serving as a barrier against microorganisms, UV radiation, loss of body fluids and stress of mechanical forces

Explain the role of normal flora that colonize the skin as a barrier function

The commensal (normal) flora protects against pathogens that cause skin infections including STAPHYLOCOCCUS and STREPTOCOCCUS by competing for nutrients and blocking the attachment of common pathogens from attaching to the epithelium of the skin

Describe how hyperkeratosis is distinct pathogenic mechanisms for psoriatic skin lesions

Hyperkeratosis: keratinocyte growth outpaces the slough rate which leads to hyperkeratosis, leading to skin lesions

Describe how epidermal inflammation is a distinct pathogenic mechanisms for psoriatic skin lesions

Epidermal inflammation: abnormal immune response leads to excessive inflammation

Describe how abnormal keratinocyte differentiation is a distinct pathogenic mechanisms for psoriatic skin lesions

Abnormal keratinocyte differentiation: produces more keratin than normal, leading to abnormal retention of the nuclei. Keratinocytes do not adhere or stick to each other properly, which causes breaks in the epidermis, leading to silvery scaly lesions.

Describe how capillary beds are affected in psoriatic lesions and how they contribute to the clinical presentation of psoriatic lesions.

Inappropriate immunologic response triggers inflammation which further recruits immune cells and keratinocyte hyperproliferation

Angiogenic factors (ex: VEGF from macrophages) are released to account for the increased cell metabolism from the keratinocyte hyperproliferation.

VEGF causes increased vascularization and capillary dilation in the dermis

Dilation of the capillaries results in erythematous lesions found in Psoriasis.

Describe hyperproliferation as it relates to psoriatic skin lesions

The release of cytokines leads to increased keratinocyte proliferation and recruits additional immune cells, leading to inflammation

List the inflammatory cytokines associated with plaque psoriasis

TNF-alpha, IFN-gamma, IL-12, IL-17 and IL-22

List three factors, mechanisms or environmental agents that may trigger psoriatic lesions.

Trauma, stress, dietary factors, and/or previous infection. These all break down skin barriers and could increase the presentation of Psoriatic skin lesions

Describe how skin barrier abnormalities, defects in innate immunity and the skewed adaptive responses are involved in atopic dermatitis, specifically eczema

In Atopic Dermatitis, increased water loss causes dryness and itchiness. An impaired epidermal barrier due to innate immunity defects allows for penetration of irritants, microbes and antigens.