Outline of Lecture
Acute and Chronic Inflammation
Possible Outcomes of Acute Inflammation
Abscess formation occurs with some bacterial or fungal infections
Progression to chronic inflammation (next)
Chronic Inflammation
CHRONIC INFLAMMATION
Definition of chronic inflammation
an inflammatory response of prolonged duration (weeks – months – years)
provoked by the persistence of the causative stimulus
simultaneous presence of acute inflammation, tissue destruction and repair
Causes of chronic inflammation
Infectious organisms that resist clearance and form a persistent infection in tissue or undrained abscess cavities
e.g mycobacterium tuberculosis, actinomycetes, treponema palidum and Staph aureus (in bone and pleural cavities)
Exposure to irritant non-living foreign material that can not be removed
implanted materials into wounds (wood splinters), inhaled materials (silica, asbestos), deliberately introduced material (surgical suture material or prosthesis)
Potentially normal tissue components as seen in auto-immune diseases
Beta islet cell in diabetes mellitus type I, Acetyl cholin receptor in Myastenia gravis
Characteristics of chronic inflammation
Infiltration of mononuclear cells
Tissue destruction
Healing with scar formation and fibrosis
Chronic inflammation
Lymphocyte, macrophage, plasma cell (mononuclear cell) infiltration
Tissue destruction by inflammatory cells
Attempts at repair with fibrosis and angiogenesis (new vessel formation)
When acute phase cannot be resolved
Persistent injury or infection (ulcer, TB)
Prolonged toxic agent exposure (silica)
Autoimmune disease states (RA, SLE)
The Players (mononuclear phagocyte system)
Macrophages
Scattered all over (microglia, Kupffer cells, sinus histiocytes, alveolar macrophages, etc.
Circulate as monocytes and reach site of injury within 24 – 48 hrs and transform
Become activated by T cell-derived cytokines, endotoxins, and other products of inflammation
The Players
T and B lymphocytes
Antigen-activated (via macrophages and dendritic cells)
Release macrophage-activating cytokines (in turn, macrophages release lymphocyte-activating cytokines until inflammatory stimulus is removed)
Plasma cells
Terminally differentiated B cells
The Players
Produce antibodies
Eosinophils
Found especially at sites of parasitic infection, or at allergic (IgE-mediated) sites
The dominant cellular player in chronic inflammation is the tissue macrophage
In chronic inflammation
macrophage accumulation persists by different mechanisms
Continued recruitment of monocytes from the circulation
Local proliferation
Prolonged survival and immobilization
Outcome of chronic inflammation
Ulcers
Fistulas
Granulomatous diseases
Fibrotic diseases
and combinations of the above
Examples of chronic inflammatory diseases
Tuberculosis
Sarcoidosis
Rheumatoid arthritis and other connective tissue diseases
Inflammatory bowl diseases (Crohns disease, ulcerative colitis)
Silicosis and other pneumoconioses
Peptic ulcer of the duodenum and stomach
Liver cirrhosis
Chronic Inflammation
Lymphocyte, macrophage, plasma cell (mononuclear cell) infiltration
Tissue destruction by inflammatory cells
Attempts at repair with fibrosis and angiogenesis (new vessel formation)
Unresolved acute phase
persistent injury or infection (ulcer, TB)
prolonged toxic agent exposure (silica)
autoimmune disease states (RA, SLE)
Mononuclear/ Phagocyte System
Macrophages
scattered all over (microglia, Kupffer cells, sinus histiocytes, alveolar macrophages)
circulate as monocytes and reach site of injury within 24 – 48 hrs and transform
become activated by T cell-derived cytokines, endotoxins, and other products of inflammation
T and B Lymphocytes
Antigen-activated (via macrophages and dendritic cells)
Release macrophage-activating cytokines (in turn, macrophages release lymphocyte-activating cytokines until inflammatory stimulus is removed)
Plasma Cells
Terminally differentiated B cells
Produce antibodies
Eosinophils
Found especially at sites of parasitic infection, or at allergic (IgE-mediated) sites
Lymph Nodes and Lymphatics
Lymphatics drain tissues
flow increased in inflammation
antigen to the lymph node
toxins, infectious agents also to the node
lymphadenitis, lymphangitis
usually contained there, otherwise bacteremia ensues
tissue-resident macrophages must then prevent overwhelming infection
Patterns of Acute and Chronic Inflammation
Serous
watery, protein-poor effusion (e.g., blister)
Fibrinous
fibrin accumulation
either entirely removed or becomes fibrotic
Suppurative (abscess)
presence of pus (pyogenic staph spp.)
often walled-off if persistent
Patterns of Acute and Chronic Inflammation
Serous
watery, protein-poor effusion (e.g., blister)
Fibrinous
fibrin accumulation
either entirely removed or becomes fibrotic
Suppurative (abscess)
presence of pus (pyogenic staph spp.)
often walled-off if persistent
Patterns of Acute and Chronic Inflammation
Serous
watery, protein-poor effusion (e.g., blister)
Fibrinous
fibrin accumulation
either entirely removed or becomes fibrotic
Suppurative (abscess)
presence of pus (pyogenic staph spp.)
often walled-off if persistent
Granulomatous Inflammation
Distinct pattern of chronic inflammation
Macrophage is the major player
Granuloma is a focal area of inflammation made up of macrophages, lymphocytes and plasma cells
Granulomatous Inflammation
Clusters of T cell-activated macrophages, which engulf and surround indigestible foreign bodies (mycobacteria, H. capsulatum, silica, suture material)
Resemble squamous cells, therefore called “epithelioid” granulomas
Ulcerative
Necrotic and eroded epithelial surface
Underlying acute and chronic inflammation
Trauma, toxins, vascular insufficiency
Systemic Effects
Fever
one of the easily recognized cytokine-mediated (esp. IL-1, IL-6, TNF) acute-phase reactions including
anorexia
skeletal muscle protein degradation
hypotension
Leukocytosis
elevated white blood cell count
Systemic Effects
bacterial infection (neutrophilia)
parasitic infection (eosinophilia)
viral infection (lymphocytosis)
