1. Chronic Inflammation
Definition:
Inflammation of prolonged duration in which active inflammation,
tissue injury and the healing proceed simultaneously
Causes:
Persistent Infections
Ex. Treponema palladium (causative organism of syphilis)
Organism of low toxicity and evoke an immune reaction =
delayed hypersensitivity
Prolonged Exposure to toxic Agents
Autoimmunity
Ex. Autoimmune diseases
2. Chronic Inflammation
Morphologic Features:
Infiltration with mononuclear cells (macrophages,
lymphocytes & plasma cells)
indicates persistent reaction to injury
Tissue destruction
Done by way of Inflammatory cells
Repair involving angiogenesis and fibrosis
Attempt to replace lost tissue
5. Mechanisms of macrophage accumulation during
Chronic Inflammation
Continued recruitment of monocytes from the
circulation
Most important source for macrophages
Local proliferation of macrophages from the blood
stream
Immobilization of macrophages within the site of
inflammation
Cytokines and oxidized lipids can cause
immobilization
7. Other Cells of Chronic Inflammation
Infiltration with mast cells, lymphocytes and plasma
cells
Lymphocytes
Mobilization in antibody – mediated response
Mast Cells
Widely distributed in connective tissues and participate in both
acute and persistent inflammatory reactions
Binds the Fc portion of the IgE antibody
Plasma Cells
Produce antibody directed either against persistent antigen in
the inflammatory site or against altered tissue components
Eosinophils
parasitic infections
Mediated by IgE
Eotaxin – a chemokine that has the ability to prime eosinophils for
chemotaxis
8. Granulomatous inflammation
It’s a pattern of chronic inflammatory reaction in
which the predominant cells are
Aggregations of macrophages having an enlarged,
squamous cell-like appearance (called Epitheloid
macrophages)
GRANULOMA = Nodular collection of
Epitheloid macrophages surrounded by a rim of
LYMPHOCYTES
It’s a focal area of Granulomatous inflammation
In an H&E stain can see:
Epitheloid cells have pale granular cytoplasm with indistinct
boundaries
Giant cells = Epitheloid cells that fuse (Langhan’s)
Can be found in the periphery or sometimes in the center of the
granuloma
Have large mass of cytoplasm
Have 20 or more small nuclei arranged in the periphery or
haphazardly
9. Granulomatous inflammation
Types of Granulomatous Inflammation
1. Immune granulomas
Caused by insoluble particles that are capable of
inducing a cell-mediated immune response
Macrophages are transformed into Epitheloid cells and
multinucleate giant cells
Examples:
Bacteria
Tuberculosis *** (high incidence due to drug
resistant stains)
Leprosy
Parasites
Schistosomiasis (3 types)
Fungi
Histoplasmosis
Blastomycosis
10. Granulomatous inflammation
2.Foreign Body Granulomas
Don’t incite either an inflammatory or immune
response.
Epitheloid cells and giant cells are apposed to the
surface and encompass the foreign body.
The foreign body is usually found in the center of the
granuloma.
Examples:
Metal/Dust
Berylliosis
Silicosis
Foreign body
Splinter
Suture
11. Granulomatous inflammation
3 Sarcoidosis
Bad systemic disease, probably autoimmune disease
Etiologic agent is unknown
12. LYMPHATICS IN INFLAMMATION
Secondary line of defense
Lymph flow is increased in inflammation
and helps drain the edema fluid
Lymphangitis
Lymphadenitis
13. Third line of defense
organisms gain access to the vascular circulation-
Bacteremia
next line of defense
Phagocytic cells of the liver, spleen, and bone
marrow
heart valves, meninges, kidneys, and joints are
favored sites of implantation for blood-borne
organisms
14. Systemic Effects of Inflammation
Infections→ reactions to cytokines
↓
Acute phase response or the systemic
inflammatory response syndrome (SIRS)
Acute phase response consists of
15. Acute phase response
Fever-elevation of body temperature by 1° to
4°C
pyrogens stimulate prostaglandin synthesis
in the vascular and perivascular cells of the
hypothalamus
exogenous pyrogens (LPS)
endogenous pyrogens (TNF, IL-1)
16. 1.Fever
PGE2 via neurotransmitters such as cyclic AMP
↓
Reset the temperature set-point at a higher level
↓
Fever
↓
Fever induce heat shock proteins that enhance
lymphocyte responses to microbial antigens
17. 2.Acute-phase proteins
C-reactive protein (CRP)
Fibrinogen
Serum amyloid A protein (SAA)
Synthesised by hepatocytes
Synthesis is by upregulated by cytokines
IL-6 (for CRP and fibrinogen)
IL-1 or TNF (for SAA)
18. 2.Acute-phase proteins
CRP and SAA act as opsonins helps in
clearing
Necroticcell nuclei
Microbial cell walls
Unlimited production of SAA - secondary
amyloidosis in chronic inflammation
19. 3.Leukocytosis
Common feature of inflammatory reactions
Bacterial infection
Usually 15,000 or 20,000 cells/μl,
20. 3.Leukocytosis contd…
A) Accelerated release of cells from the bone
marrow post - mitotic reserve pool
↓
(shift to the left) by cytokines
B) Colony stimulating factors cause increase
production of WBC
22. Other features of APR
Effects of cytokines on brain cells
Increased pulse and blood pressure
Decreased sweating,
Rigors (shivering)
Chills (search for warmth)
Anorexia
Malaise
23. Sepsis
Sepsis ;- severe bacterial infection
Large amounts of LPS & TNF
Multiple small thrombi by expressing Tissue
Factor (TF) on Endothelial cells (EC)
Septic shock – Triad
1. Liver failure – no Gluconeogenesis (Hypoglycemia)
2. Loss of perfusion pressure & heart failure –
hemodynamic shock
3. Disseminated Intravascular Coagulation (DIC) –
Multiple Thrombi in circulation & Fibrin split
products
Multi Organ Failure
Mainly Lung , Liver also Kidney & Bowel
24. Consequences of impaired inflammation
Defective inflammation Excess Inflammation
↑ susceptibility to Allergies
infection Important in
Delay in wound healing Cancer
Tissue damage Atherosclerosis
Fibrosis as a sequel of
chronic infections,
metabolic conditions