2024 - Chronic Inflammation - year 1

Definition:
- Prolonged inflammation with delayed response.
- Results from a balance between tissue damage due to persistent stimuli and the body's attempt to repair.
- Predominantly involves lymphocytes and macrophages.

Onset:
- Begins gradually and is usually preceded by acute inflammation.
- Triggered by persistent or recurrent stimuli.

Progression Examples:
- Abscess formation (e.g., acute osteomyelitis progressing to chronic osteomyelitis).
- Indigestible materials (e.g., wood or surgical sutures in wounds).
- Recurrent episodes of acute inflammation

Causes:
- Persistent infections (e.g., Mycobacterium tuberculosis, Treponema pallidum, fungi).
- Prolonged exposure to toxic agents (e.g., silica, asbestos).
- Autoimmune diseases (e.g., Rheumatoid arthritis, Systemic Lupus Erythematosus).
- Diseases of unknown etiology (e.g., Inflammatory bowel disease).

- Mononuclear cells (macrophages, lymphocytes, and plasma cells).
- Tissue destruction.
- Repair processes (granulation tissue formation, angiogenesis, and fibrosis).

Origin:
- Derived from blood monocytes; found as tissue macrophages in different organs.
  - Examples: Kupffer cells (liver), sinus histiocytes (spleen and lymph nodes), alveolar macrophages (lungs), microglia (CNS), osteoclasts (bone).
Role in Inflammation:
- Main effector cells in chronic inflammation.
- Involve in the phagocytosis of pathogens and tissue remodelling.
- Activation through cytokines and bacterial endotoxins.

Production:
- Produced in the bone marrow, mature in the thymus.
Types:
- CD4 helper cells (MHC class II)
- CD8 cytotoxic cells (MHC class I).
Functions:
- Regulate macrophage activity and release lymphokines for immune response.

Production:
- Produced in the bone marrow and activated to form plasma cells.
Function:
- Plasma cells produce antibodies following antigen encounter, possessing a high quantity of rough endoplasmic reticulum.

Natural Killer (NK) Lymphocytes:
- Eliminate viruses and bacteria.
Eosinophils:
- Common in allergies and effective against parasites; contribute to tissue damage with major basic protein (MBP).
Mast Cells and Basophils:
- Have IgE receptors.
- IgE stimulation triggers release of inflammatory mediators like heparin and proteinases.
Dendritic Cells:
- Key antigen-presenting cells that activate naive T cells to initiate immune response.
- Bind antigens to MHC class II and present them to lymphocytes for activation

Definition:
- A specific form of chronic inflammation characterized by aggregation of macrophages (epithelioid macrophages).
- Granulomas consist of nodular collections of epithelioid macrophages surrounded by lymphocytes and giant cells.
Causes:
- Response to infections (e.g., tuberculosis), foreign bodies, tumors, or unknown etiology (e.g., sarcoidosis).

Occurs in response to poorly digestible foreign material:
- Exogenous: Splinters, sutures, graft materials.
- Endogenous: Keratin, hair shafts (e.g., in pilonidal sinus).

Involves interactions between CD4 T helper cells and macrophages:
- Macrophages present antigens via MHC II to CD4 helper T cells, activating them.
- Results in cytokine production (e.g., IL-2, IFN-γ).
Associated Conditions: TB, fungal infections, sarcoidosis.

Foreign Body Granuloma:
- Macrophages cluster around foreign material.
- Presence of multinucleated giant cells with disorganized nuclei.

Caused by Mycobacterium tuberculosis.
Induces type IV hypersensitivity; primarily affects lungs and lymph nodes.
Histological Features:
- Caseating granuloma, central necrosis.
- Presence of epithelioid macrophages, Langhans giant cells, T-helper cells, plasma cells, and peripheral suppressor T cells and fibroblasts.
Diagnostic Techniques: ZN stain, culture, fluorescent staining with auramine, PCR.

Granulomatous condition of unknown origin, more common in young adults, especially Blacks.
Histological Features:
- Non-caseating naked granuloma.
- Presence of Schaumann bodies (concentric calcifications) and asteroid bodies.

Serous Inflammation:
- Accumulation of thin fluid; can occur in skin blisters or body cavities.
Fibrinous Inflammation:
- Characterized by fluid and fibrin accumulation; may result in organization.
Suppurative Inflammation:
- Characterized by the presence of pus, potentially leading to abscess formation.

Abscess:
- Localized pus collection, consisting of necrotic tissue and microorganisms.
Ulcer:
- Local defect in the epithelial surface, resulting from cell shedding and tissue loss.
Sinus:
- Tract lined with granulation tissue, often due to chronic inflammation.
Fistula:
- Abnormal communication between two surfaces, track open at both ends such as gastrointestinal in Crohn's disease.

Acute Phase Response:
- Systemic response due to inflammatory mediators from leukocytes and hepatocytes in reaction to infection or injury.

Pyrexia:
- Fever induced by pyrogens affecting the hypothalamus via IL-1 and TNF-α.
Acute Phase Proteins:
- Liver-produced proteins such as C-reactive protein (CRP) and fibrinogen influencing blood parameters (increased ESR).
Leukocytosis:
- White blood cell count elevation(4-8 to 15-20)
- extreme elevations may indicate leukemoid reactions or leukemia
General Symptoms:
- Increased pulse and blood pressure, sweating, anorexia, and malaise.
Severe Consequences:
- Sepsis