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
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
Chronic Inflammation
Mononuclear Phagocyte System
Circulating blood monocytes →Tissue macrophages
↓
Kupffer cells (liver)
Sinus Histiocytes (spleen)
Microglia (CNS)
Alveolar Macrophages (lung)
Maturation of Mononuclear Phagocytes
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
Effects of Macrophage Activation
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
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
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
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
Granulomatous inflammation
 3 Sarcoidosis
 Bad systemic disease, probably autoimmune disease
 Etiologic agent is unknown
LYMPHATICS IN INFLAMMATION

 Secondary line of defense

 Lymph flow is increased in inflammation
and helps drain the edema fluid
 Lymphangitis
 Lymphadenitis
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
Systemic Effects of Inflammation
Infections→ reactions to cytokines
↓
Acute phase response or the systemic
inflammatory response syndrome (SIRS)
Acute phase response consists of
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)
 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
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)
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
3.Leukocytosis

Common feature of inflammatory reactions

Bacterial infection
Usually 15,000 or 20,000 cells/μl,
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
3.Leukocytosis contd…

Most bacterial infections induce Neutrophilia

Viral infections-Lymphocytosis
Typhoid fever , Rickettsiae-Leukopenia
bronchial asthma, hay fever, and parasitic
infestations- Eosinophilia
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
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
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