Inflammation Mechanisms and Responses

Chronic inflammation is a prolonged inflammatory response lasting weeks to years.
It involves ongoing inflammation, tissue damage, and healing, often with fibrosis.
It is characterized by infiltration of mononuclear cells (macrophages, lymphocytes, plasma cells, and eosinophils), tissue destruction and repair.
Can be a continuation of or independent from acute inflammation

A rapid response to injury.
Macroscopic features include redness, swelling, heat, and pain.
Microscopic features include vascular dilation, exudate, and neutrophil emigration.
Mediated by short-lived chemical mediators (some manipulatable by drugs).
Neutrophils are the primary phagocytes, engulfing and degrading bacteria and dead tissue.
Phagocytosis is enhanced by opsonisation of particles, e.g. antibody or complement.
Bacterial killing is largely oxygen dependent.

Rapid response of living tissue to any injury.
Macroscopic (naked-eye) features include: redness, swelling, heat, pain & loss of function.
Microscopic features include vascular dilation and exudate leakage into tissues, neutrophil migration.
Changes are regulated by short-lived chemical mediators, some of which are treatable with drugs.
Neutrophils are fast-acting, short-lived phagocytes, ingesting and breaking down bacteria and dead tissue.
Phagocytosis is improved by opsonisation (marking particles for phagocytosis).
Bacterial killing heavily relies on oxygen.

Cells and their functions in chronic inflammation.
Role of macrophages in chronic inflammation.
Conditions associated with chronic inflammation and types of inflammation
Possible chronic inflammation complications.
Relevant clinical situations, their causative factors, complications, and treatments.
Granulomatous inflammation: a type of chronic inflammation, described as Tuberculosis and leprosy, Sarcoidosis, syphilis, foreign body reactions

Derived from blood monocytes.
Accumulate due to recruitment from blood, mitotic division, and immobilization by cytokines (Macrophage inhibitory factor).
Activation occurs once extravasated (moved from blood vessel to tissue).
Macrophages are activated by interferon gamma (IFN-γ) secreted by sensitized T-cells and bacterial endotoxins.
Phagocytosis: ingest, engulf microbes and cellular debris, and destroy using oxygen or oxygen-independent mechanisms.
Initiate tissue repair and contribute to fibrosis and scar formation.
Secrete inflammatory mediators like cytokines (TNF, IL-1) for initiation and maintenance of inflammatory reactions,
Display antigens to T-lymphocytes, responding to T-cell signaling.
Important role in chronic inflammation clearance of debris and initiating tissue repair/healing.

Sometimes called "chronic inflammatory cells."
A normal component of many tissues.
Primarily involved in immune responses (immunological functions).
B-lymphocytes produce antibodies.
T-lymphocytes are for immune control and specific cytolytic (cell-killing) functions.

Plasma cells: differentiated antibody-producing B-lymphocytes (implying chronicity).
Eosinophils: involved in allergic reactions, parasite infestations, and some tumours.
Fibroblasts/myofibroblasts: recruited by macrophages, they create collagen.
These cells are crucial for the complex responses in chronic inflammatory processes.

Granulomas are localized collections of immune cells, usually in chronic inflammation.
Arising when a low-grade antigenic stimulation persists.
Often present in various chronic inflammatory conditions.
Associated with a prolonged inflammatory reaction.

Fibrosis (e.g., in chronic cholecystitis, as a result of repeated attacks).
Impairment of function (e.g., in chronic inflammatory bowel disease).
Rarely, increased function (e.g., Graves disease).
Atrophy (e.g., in gastric mucosa, adrenal glands).
Stimulation of immune response (macrophage-lymphocyte interactions).
Chronic inflammation can result in various pathological effects, including structural changes and functional alterations.

Fibrosis
Impaired function and atrophy
Stimulation of immune response
Understanding the significance of chronic inflammation is crucial for diagnosis and treatment.

Primary Tuberculosis: Infection in previously uninfected individuals, usually affects mid-zone lungs, often forming Ghon focus.
Secondary Tuberculosis: Re-activation or recurring infection in a previously infected individual, commonly starts at apical lung
Ghon focus & complex
Outcomes: Often scarring with lingering bacteria. Possible progressive primary tuberculosis with massive hilar lymph nodes, tuberculous bronchopneumonia, or miliary tuberculosis.

Morphology of most cases isn't specific, though the proportions of cell types can vary
Some examples of variation include Rheumatoid arthritis (plasma cells), chronic gastritis (lymphocytes), Leishmaniasis (macrophages).
Varied cell types reflect the complex nature of the inflammatory responses.

Although characteristic of acute inflammation, neutrophils can persist and be seen in chronic inflammation due to persistent microbes, necrotic cells, or mediators produced by macrophages.
Their presence may indicate unresolved issues or ongoing challenges.