Chronic Inflammation and Granuloma

• Definition: reaction which is slow on onset and prolonged in duration.

• Characteristic histological features:

1. Greater tissue destruction than acute inflammation (necrosis and

hemorrhage).
2. Mononuclear infiltrates (lymphocytes, plasma cells, and
macrophages).
3. Granulation tissue formation and scarring (fibrosis) with little or
absent exudate.
 Causes of chronic inflammation
• Acute infections usually are self-limiting and rapidly
controlled by the host defenses. In contrast, chronic
inflammation may last for weeks, months, or even years. It
may develop during a recurrent or progressive acute
inflammatory process or from low-grade, smoldering
responses that fail to evoke an acute response
• Progression from acute inflammation.

• Primary chronic inflammation;

 Causes of primary chronic inflammation

• 1- Persistent infections
– Organisms usually of low toxicity that invoke delayed
hypersensitivity reaction - M. tuberculosis and T. pallidum
causes granulomatous reaction

• 2- Prolonged exposure to potentially toxic agents

– Exogenous agents include silica which causes silicosis

– Endogenous causes include atherosclerosis

• 3- Autoimmunity
– Auto-antigens provoke self- immune responses that cause
chronic inflammatory diseases like Rheumatoid Arthritis,
SLE.

– Responses against common environmental substances

cause chronic allergic diseases, such as bronchial asthma
 Patterns of chronic inflammation

• 1-Nonspecific Chronic Inflammation

• involves a diffuse accumulation of macrophages and

lymphocytes at the site of injury. Ongoing chemotaxis causes
macrophages to infiltrate the inflamed site
• These mechanisms lead to fibroblast proliferation, with
subsequent scar formation. For example, scar tissue resulting
from chronic inflammation of the bowel causes narrowing of
the bowel lumen.
• 2- Granulomatous Lesions
• . A granuloma typically is a small, 1- to 2-mm lesion in which there is a
massing of macrophages surrounded by lymphocytes. These modified
macrophages resemble epithelial cells and sometimes are called epithelioid
cells. have a pale pink granular cytoplasm with indistinct cell boundaries, the
nucleus is vesicular and oval or elongate , often appearing to merge into one
another as multinucleated giant cells:
1. Langerhans type: horse-shoe appearance of nuclei. It is characteristic for TB.
2. Foreign body type: random arrangement of nuclei. It is found with Asbestosis
and Silicosis.
• Granulomatous inflammation is associated with

• foreign bodies such as splinters, sutures, silica, and asbestos

• microorganisms that cause tuberculosis, syphilis,

sarcoidosis, deep fungal infections, and brucellosis.
• These types of agents have one thing in common: they are
poorly digested and usually are not easily controlled by
other inflammatory mechanisms.
Granulomatous Lymphadenitis
Foreign body giant cell Langerhans giant cell
 Causes of granulomas
Disease Cause Tissue Reaction
Tuberculosis Mycobacterium Caseating granuloma (tubercle): focus of activated
tuberculosis macrophages (epithelioid cells), rimmed by fibroblasts,
lymphocytes, histiocytes, occasional Langhans giant
cells; central necrosis with amorphous granular debris;
acid-fast bacilli

Leprosy Mycobacterium leprae Acid-fast bacilli in macrophages; noncaseating granulomas

Syphilis Treponema pallidum microscopic to grossly visible lesion, enclosing wall of

histiocytes; plasma cell infiltrate; central cells necrotic
without loss of cellular outline

Cat-scratch Gram-negative Rounded or stellate granuloma containing central granular

disease bacillus debris and recognizable neutrophils; giant cells
uncommon
Sarcoidosis Unknown etiology Noncaseating granulomas with abundant activated
macrophages

Crohn disease Immune reaction Occasional noncaseating granulomas in the wall of the
(inflammatory against intestinal intestine, with dense chronic inflammatory infiltrate
bowel bacteria, self-
disease) antigens
 Cellular co-operation of CI
• Lymphocytes; T lymph, B lymph.
• B lymph; plasma cells, produce Abs.
• T lymph; cell mediated immunity, produce cytokine.
• Cytokine activities;
1) Recruitment of macrophages& other lymphocytes.
2) Production of inflammatory mediators.
3) Destruction of target cells- perforin.
4) Interferon gamma (anti viral)
 Macrophages in chronic inflammation

• Derived from blood monocytes; CT Histiocytes,

alveolar mac, kupffer cells, melanophage,

osteoclast, microglia.

• Histiocytic giant cells types; 1- langhan’s cell. 2-

foreign body type.

 Acute-Phase Response

• A systemic effects called the acute-phase response which

usually begins within hours or days of the onset of
inflammation or infection, includes: changes in the
concentrations of plasma proteins , increased erythrocyte
sedimentation rate (ESR), fever , increased numbers of
leukocytes , skeletal muscle catabolism

These responses are generated after the release of the

cytokines, IL-1, IL-6, and TNF-α.
• These cytokines affect the thermoregulatory center in the
hypothalamus to produce fever, the most obvious sign of the
acute-phase response. IL-1 and other cytokines induce an
increase in the number and immaturity of circulating
neutrophils by stimulating their production in the bone
marrow.
• Lethargy, a common feature of the acute-phase response,
results from the effects of IL-1 and TNF-α on the central
nervous system
• Bacterial infections produce a relatively selective increase in

neutrophils (neutrophilia), whereas parasitic and allergic

responses induce eosinophilia. Viral infections tend to produce

neutropenia (decreased numbers of neutrophils) and

lymphocytosis.
• The liver increases the synthesis of acute-phase proteins such as
fibrinogen and C-reactive protein (CRP) that serve several different
nonspecific host defense functions
• The change in the types of plasma proteins contributes to the increased
ESR.
• The metabolic changes, including skeletal muscle catabolism, provide
amino acids that can be used in the immune response and for tissue repair.
• The total systemic process coordinates various activities in the body to
enable an optimum host response
 Systemic effects of inflammation

• Pyrexia.
• symptoms; malaise, anorexia & nausia.
• Wight loss.
• Reactive hyperplasia of RES.
• Haematological changes;

1- high ESR.

2- leukocytosis.

3- anaemia.

4- amyloidosis.