pathology

Body Defense Mechanisms Against Injury

When tissue is injured, the body activates general defense mechanisms.

Defense Mechanisms Include

The skin and mucous membranes; The mononuclear phagocyte system (MPS); The inflammatory response; The immune system

Skin and Mucous Membranes

Serve as the first line of defense; Act as mechanical barriers, protecting the body from injurious agents

Mononuclear Phagocyte System (MPS)

Consists of monocytes and macrophages, including their precursor cells; Also known as the reticuloendothelial system (RES); Functions include the recognition and phagocytosis of foreign material; Macrophages can be fixed or free (mobile) and are found in various tissues

Connective Tissue Macrophages

Histiocytes

Liver Macrophages

Kupffer Cells

Lung Macrophages

Alveolar Macrophages

Spleen Macrophages

Free and Fixed Macrophages

Bone Marrow Macrophages

Fixed Macrophages

Lymph Nodes Macrophages

Free and Fixed Macrophages

Bone Tissue Macrophages

Osteoclasts

Central Nervous System Macrophages

Microglial Cells

Peritoneal Cavity Macrophages

Peritoneal Macrophages

Pleural Cavity Macrophages

Pleural Macrophages

Skin Macrophages

Histiocytes, Langerhans Cells

Synovium Macrophages

Type A Cells

Inflammatory Response Definition

A sequential reaction to cell injury; Neutralizes and dilutes the inflammatory agent, removes necrotic materials, and establishes an environment for healing and repair

Phases of the Inflammatory Response

Vascular Response; Cellular Response

Vascular Response

Initial response involving vasodilation and increased vascular permeability

Cellular Response

Involves the extravasation of leukocytes from the blood to the tissue

Margination

Adherence of leukocytes to the endothelium

Transmigration

Movement through the vascular wall (diapedesis)

Chemotaxis

Directed migration towards a chemical stimulus

Phagocytosis

Ingestion and degradation of foreign material

Phagocytosis Step 1

Recognition and attachment of particles

Phagocytosis Step 2

Engulfment and formation of phagolysosome

Phagocytosis Step 3

Killing or degradation using oxygen-independent mechanisms (lysosomal enzymes); Oxygen-dependent mechanisms (reactive oxygen species)

Chemical Mediators of Inflammation

Originating from plasma or cells such as neutrophils, macrophages, lymphocytes, basophils, mast cells, and platelets

Histamine

Stored in granules of basophils, mast cells, platelets; Causes vasodilation and increased vascular permeability by stimulating contraction of endothelial cells and creating widened gaps between cells

Serotonin

Stored in platelets, mast cells, and enterochromaffin cells of the GI tract; Causes increased vasodilation and increased vascular permeability by stimulating endothelial cells and creating widened gaps between cells; Stimulates smooth muscle contraction

Kinins (Bradykinin)

Produced from prekallikrein and kininogen as a result of activation of Hageman factor (XII) of clotting system; Causes vasodilation and blood vessel permeability; Stimulates pain

Complement Components (C3a, C4a, C5a)

Anaphylaxis agents generated from complement pathway activation; Stimulate histamine release; Stimulate chemotaxis

Fibrinopeptides

Produced from activation of the clotting system; Increases vascular permeability; Stimulates chemotaxis for neutrophils and monocytes

Prostaglandins

Produced from arachidonic acid; PGF and PGE1 cause vasodilation; LTB4 stimulates chemotaxis

Formation of Exudates

Exudates consist of fluids and leukocytes that move from circulation to the injury site; The nature and quantity depend on the injury type and severity

Types of Inflammatory Exudates

Serous; Catarrhal; Fibrinous; Purulent; Hemorrhagic

Serous Exudates

Result from outpouring of fluid that has low cell and protein content; Seen in early stages of inflammation or when injury is mild; Examples include skin blisters and pleural effusion

Catarrhal Exudates

Found in tissues where cells produce mucus; Mucus production is accelerated by inflammatory response; Example: runny nose associated with URTI

Fibrinous Exudates

Occur with increasing vascular permeability and fibrinogen leakage into tissue space; Excessive amount of fibrin coating tissue surfaces may cause them to adhere

Hemorrhagic Exudates

Result from rupture or necrosis of blood vessel walls; Consists of RBCs that escape into tissue

Clinical Manifestations of Inflammation

Local Response; Systemic Response

Local Response Redness (Rubor)

Hyperemia from vasodilation

Local Response Heat (Calor)

Increased metabolism at inflammatory site

Local Response Pain (Dolor)

Change in pH; Change in ionic concentration; Nerve stimulation by chemicals (e.g. histamine, prostaglandins); Pressure from exudates

Local Response Swelling (Tumor)

Fluid shift to interstitial spaces; Fluid exudate accumulation

Local Response Loss of Function (Functio Laesa)

Swelling and pain

Systemic Response Leukocytosis

Increased release of leukocytes

Systemic Response Symptoms

Malaise; Nausea; Anorexia; Fatigue

Fever in Inflammation

Cytokine release (IL-1, IL-6, TNF) triggers fever

Classification of Inflammation Acute

Involves inflammation that lasts 3 days to 3 weeks and usually leaves no residual damage

Classification of Inflammation Sub-Acute

Similar to acute but lasts longer

Classification of Inflammation Chronic

Persists for weeks, months, or years due to the persistence of the injurious agent

Cellular Adaptation

Reversible changes in cell size, number, phenotype, metabolic activity, or function in response to stress; caused by increased demand, chronic irritation, hypoxia, or hormonal stimulation

Physical Agents

Trauma, burns, pressure, irradiation.

Chemical Agents

Poisons, drugs, simple compounds.

Microorganisms

Bacteria, viruses, fungi, parasites.

Hypoxia

Inadequate oxygen in the blood or decreased tissue perfusion.

Genetic Defects

inborn errors of metabolism or gross malformation.

Nutritional Imbalances

Under-nutrition or over-nutrition.

Immunologic Reactions

Hypersensitivity reactions.

Increased Concentrations

Accumulation of normal cellular constituents.

Abnormal Substances

Accumulation of abnormal substances.

Change in Size or Number

Alteration in cellular size or number.

Lethal Change

Progression to cell death.

Atrophy

Decrease in cell size due to reduced workload, loss of nerve supply, decreased blood supply, inadequate nutrition, or loss of hormonal stimulation.

Hypertrophy

Increase in cell size resulting in increased tissue mass without increase in cell number; caused by increased workload or hormonal stimulation

Hyperplasia

Increase number of cells; Increase in tissue mass due to an increase in cell number

Metaplasia

Reversible change where one adult cell type is replaced by another more suitable type for the environment.

Dysplasia

Loss of architectural orientation of one cell; Atypical changes in cells, often linked to chronic irritation and a precursor to malignancy.

Reversible Cell Injury

Can be corrected when the stimulus is removed (e.g., ischemia).

Irreversible Cell Injury

Cannot be corrected after the stimulus is removed, leading to cell death (e.g., infarction, ischemic necrosis).

Necrosis

Pathologic cell or tissue death due to injury; caused by ischemia, toxins, infections, or trauma

Coagulative Necrosis

Preservation of cell structure with loss of nucleus.

Liquefactive Necrosis

Enzymatic dissolution of necrotic cells, common in brain tissue.

Neoplasm

New abnormal cell growth (tumor)

Benign Tumor

Abnormal cell division without metastasis.

Malignant Tumor

Abnormal cell division with local invasion, metastasis, and recurrence (cancer).

Carcinogenesis

Process of cancer cell formation

Metastasis

Spread of cancer cells to distant sites.

Carcinogen

Agent capable of causing cancer; Substances inducing neoplastic growth (e.g., polycyclic aromatic hydrocarbons, aromatic amines).

Chemical Carcinogens

Substances that induce cancer; examples include polycyclic aromatic hydrocarbons, aromatic amines, alkylating agents

Physical Carcinogens

Agents such as ionizing radiation and ultraviolet radiation that damage DNA

Viral Carcinogens

Oncogenic viruses; examples include HPV, EBV

Urticaria

Welts; Hives due to type I hypersensitivity; Erythematous skin lesions; causes include allergens, infections, stress, disease, excessive perspiration

Psoriasis

Chronic autoimmune inflammatory skin disease; caused by T-lymphocytes–mediated immune response; triggers include stress, infection, cold, trauma

Folliculitis

Infection or inflammation of hair follicles; caused by Staphylococcus aureus, friction, occlusion

Furuncle

Boils; Deep follicular infection forming a boil; cluster of caruncles; caused by Staphylococcus aureus

Impetigo

Highly contagious skin infection causing vesicles that rupture and form a honey-colored crust; triggered by Staphyloccoci

Cellulitis

Infection deep in the dermis and subcutaneous tissue; direct invasion of pathogens

Necrotizing Fasciitis

Flesh-eating bacteria; Generally Rare, bronze/purple colored patch, aggressive infection destroying skin, fat, and muscle.

Herpes Simplex Virus Type 1 (HSV-1)

Affects lips, mouth, face; transmitted by saliva; (childhood); remains dormant in trigeminal nerve - still in the bodyt

Herpes Zoster

Reactivation of varicella-zoster virus; causes shingles; 2nd time chicken pox

Verrucae

Warts caused by human papillomavirus; transmitted by direct contact

Tinea

Superficial fungal infections (e.g., Tinea capitis (scalp), Tinea corporis(ring worm), Tinea pedis (athletes foot), Tinea unguium(nails))

Scabies

Mite infestation (Sarcoptes scabiei); transmitted by close contact; causes intense pruritus

Pediculosis

Lice infestation of scalp, body, or pubic area; transmitted by close contact or fomites

First-Degree Burn

Superficial burn of epidermis; caused by brief heat exposure or sunburn; presents with erythema and pain

Second-Degree Burn

Partial-thickness burn of epidermis and dermis; caused by scalds or flames; presents with blisters

Third-Degree Burn

extend into deeper tissues; Full-thickness burn; caused by prolonged heat, chemicals, or electricity; presents with leathery, painless skin