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Chronic inflammation md pathology robbins based answer

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Robbins pathology chronic inflammation definition causes cells morphologic features

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Chronic inflammation

Definition: Chronic inflammation is a prolonged response, lasting weeks to months, in which active inflammation, tissue injury, and repair occur simultaneously. It may follow acute inflammation or arise insidiously without a preceding acute phase.
Robbins, Cotran & Kumar Pathologic Basis of Disease, pp. 86-87.

Causes

  1. Persistent infections
    • Organisms difficult to eradicate, especially mycobacteria, viruses, fungi, and parasites.
    • May produce a granulomatous pattern.
    • An acute infection may occasionally fail to resolve and become chronic, for example a chronic lung abscess.
  2. Immune-mediated and hypersensitivity diseases
    • Autoimmune disorders: e.g., rheumatoid arthritis, multiple sclerosis.
    • Persistent or dysregulated immune response to microbes: e.g., inflammatory bowel disease.
    • Allergic diseases: e.g., bronchial asthma.
  3. Prolonged exposure to toxic agents
    • Exogenous: silica inhalation causing silicosis.
    • Endogenous: lipid deposition in arterial walls contributing to atherosclerosis.

Morphological features

The three characteristic features are:
  1. Mononuclear cell infiltration
    • Mainly macrophages, lymphocytes, and plasma cells.
  2. Tissue destruction
    • Caused by the persistent injurious agent and by activated inflammatory cells.
  3. Healing by connective-tissue replacement
    • Angiogenesis: formation of new small vessels.
    • Fibrosis: collagen deposition and scar formation.
Mnemonic: MTF
  • Mononuclear infiltrate
  • Tissue destruction
  • Fibrosis with angiogenesis
Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 87.

Cells and mediators

1. Macrophages: the dominant cell

Macrophages derive mainly from circulating blood monocytes, which migrate into tissue and differentiate. They:
  • Phagocytose microbes and dead cells
  • Produce inflammatory mediators: TNF, IL-1, chemokines, eicosanoids
  • Cause tissue injury through reactive oxygen species, nitric oxide, lysosomal enzymes, and proteases
  • Present antigen to T lymphocytes
  • Promote repair, angiogenesis, fibrosis, and scar formation

Macrophage activation

TypeMain activatorsMajor functions
Classical activation, M1-likeMicrobial products/TLR ligands, IFN-gamma, foreign materialMicrobial killing; secretion of pro-inflammatory cytokines; tissue injury
Alternative activation, M2-likeIL-4, IL-13Termination of inflammation; tissue repair; fibrosis

2. Lymphocytes

T lymphocytes and macrophages maintain and amplify chronic inflammation through a feedback loop.
  • T cells recruit and activate macrophages.
  • IFN-gamma from T cells activates macrophages.
  • Activated macrophages present antigen to T cells and release cytokines, including IL-12, which further activates T cells.
  • T cells also produce TNF, IL-17, and chemokines, promoting recruitment of leukocytes and monocytes.
  • B cells/plasma cells may produce antibodies directed against persistent antigens or self-antigens.

3. Other cells

  • Eosinophils: prominent in parasitic infections and Th2-mediated allergic disorders; recruited in part by eotaxin.
  • Mast cells: can participate in chronic inflammatory reactions, especially allergic disease, by releasing mediators such as histamine and prostaglandins.
  • Neutrophils: may coexist with chronic inflammation if there are repeated acute episodes or persistent infection.
Robbins, Cotran & Kumar Pathologic Basis of Disease, pp. 87-90.

Granulomatous inflammation

A distinctive pattern of chronic inflammation, usually due to persistent agents that are difficult to eradicate.

Granuloma

A localized collection of activated macrophages, called epithelioid cells, often surrounded by lymphocytes. Epithelioid cells may fuse to form multinucleated giant cells.

Types

  1. Foreign-body granuloma
    • Caused by inert material too large to be phagocytosed, such as suture material, talc, or splinters.
    • Giant cells surround the foreign material.
    • T-cell-mediated immune response is not prominent.
  2. Immune granuloma
    • Caused by persistent T-cell-mediated immune response.
    • Th1 cells produce IFN-gamma, activating macrophages.
    • Examples: tuberculosis, leprosy, some fungal infections, sarcoidosis, and Crohn disease.

Tuberculous granuloma

A typical tubercle has:
  • Central caseous necrosis
  • Surrounding epithelioid macrophages
  • Langhans-type giant cells
  • Peripheral lymphocytes
Key point: When granulomas are identified, tuberculosis should be excluded.
Robbins, Cotran & Kumar Pathologic Basis of Disease, pp. 90-91.

Acute versus chronic inflammation

FeatureAcute inflammationChronic inflammation
Onset/durationRapid, minutes to daysProlonged, weeks to months or longer
Predominant cellsNeutrophilsMacrophages, lymphocytes, plasma cells
Main vascular responseEdema and exudationLess prominent exudation
Tissue injuryUsually mild and self-limitedOften persistent and progressive
RepairUsually follows resolutionOccurs simultaneously with inflammation
FibrosisUsually absent or limitedCommon and may dominate late stages

Exam summary

Chronic inflammation is characterized by mononuclear inflammatory infiltrate, ongoing tissue destruction, and attempts at repair by angiogenesis and fibrosis. Macrophages are the principal cells, while macrophage-T-cell interactions sustain the response. Persistent infections, autoimmune/allergic disorders, and toxic agents are the major causes.
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