Basic pathology

Dr. Mishaal
Inflammation
 CHRONIC
INFLAMMATION
 Chronic Inflammation
• Definition: Prolonged vascularized tissue
response to persistent stimulus in which active
inflammation, tissue destruction, and tissue repair
are simultaneously present for a long duration
(weeks-months-years).
• The main characteristic changes in chronic
inflammation are :
- Infiltration with chronic inflammation cells
- Tissue destruction and degeneration
- Repair and Healing process
 Chronic Inflammation etiology
• Clinical settings (etiology) of chronic inflammation:
1- Persistent infections with low toxicity & high
resistance will evoke delayed type hypersensitivity e.g.
mycobacteria, T. pallidum & certain viruses and
fungi
2- Prolonged exposure to toxic agents e.g. :
 endogenous: high lipid level, causing atherosclerosis
exogenous: inhaled silica causing lung silicosis
3- Autoimmunity e.g. rheumatoid arthritis (RA),
systemic lupus erythematosus (SLE), or immune
responses against common environmental substances
that cause allergic diseases, such as bronchial asthma.
4- Neoplasia : some forms of cancer
 Chronic Inflammation pathogenesis
• The development of chronic inflammation can
either be primary (without going through acute
inflammation), or secondary (progress from
acute inflammation)
 Primary chronic inflammation
• Primary: manifests as chronic directly without going through
acute inflammation e.g.
Resistant organism Tuberculosis, leprosy, some fungi &parasites
Chronic viral infections Chronic viral hepatitis
Endogenous materials Necrotic bone, uric acid crystals (Gout), lipid
Exogenous materials Silica, Asbestos, Beryllium, suture, foreign
body
Autoimmune disease Hashimoto’s, Rheumatoid arthritis
Allergic inflammation Bronchial asthma, atopic dermatitis
Transplant rejection Kidney transplant rejection
Primary granulomatous disease Sarcoidosis
Unknown aetiology Inflammatory bowel disease
 Secondary chronic inflammation
1. Progress from acute inflammation
- from persistence of inciting stimuli
- from suppuration (pus) that is poorly drained

2. Recurrent episodes of acute inflammation

i.e. secondary to repeated bouts of tissue injuries
e.g.
- gall-stones – chronic cholecystitis
- recurrent urinary tract infection
- poorly fixed denture
others: Rheumatoid synovitis
Acute Cholecystitis – if recurrent
it becomes chronic
 Chronic Inflammation pathogenesis
• Infiltration with Mononuclear cells (Macrophages,
Lymphocytes, Plasma cells), giant cells, and fibroblasts
proliferation.
• Macrophages can be activated by a variety of stimuli,
including cytokines e.g., IFN-γ secreted by sensitized T
lymphocytes and NK cells, bacterial endotoxins, and other
chemical mediators. Activation results in increased cell
size, and greater ability to phagocytose and kill ingested
microbes. Activated macrophages secrete a wide variety of
biologically active products that result in the tissue injury
and fibrosis. In short-term inflammation, if the irritant is
eliminated, macrophages eventually disappear (dying off
or travel through lymphatics to lymph nodes).
 Chronic Inflammation pathogenesis
In chronic inflammation, macrophage accumulation
persists, and this is mediated by the following:
1. Recruitment from circulating monocytes; a process
fundamentally similar to that of neutrophils.
2. Local proliferation of macrophages after their
emigration from the bloodstream. This is now known to
occur prominently in some chronic inflammatory
lesions, such as atheromatous plaques.
3. Immobilization of macrophages within the site of
inflammation. Certain cytokines and oxidized lipids can
cause such immobilization (migration inhibiting factors).
 Macrophage accumulation
Macrophage accumulation
 Chronic Inflammation pathogenesis
• Complex interactions between several cell
populations and their secreted mediators. Mediated
by the interaction of monocyte/macrophages with
T and B lymphocyte, plasma cells and others

• Chronic inflammatory cells and mediators are:

A- The cells :
Infiltration of the affected area with : Mononuclear
cells (Macrophages, Lymphocytes, Plasma cells),
giant cells, and fibroblasts proliferation
 Chronic Inflammation pathogenesis
B- The mediators :
• The products of activated macrophages include :
1. Acid and neutral proteases
2. Chemotactic factors
3. Reactive oxygen species
4. Complement components
5. Coagulation factors
6. Growth promoting factors for fibroblasts, blood vessels
and myeloid progenitor cells
7. Cytokines : IL-1, TNF
8. Other biologic active agents ( platelet activating
factor/PAF, interferon, amino acid metabolites)
 Chronic Inflammation pathogenesis
B- The mediators :
• The products of activated macrophages serve to
eliminate injurious agents such as microbes and to
initiate the process of repair, but are also responsible
for much of the tissue injury in chronic inflammation;
their main functions are :
- 1. Toxic substances to microbes and host cells (e.g.,
toxic O2 species, NO, and proteases)
- 2. Chemo-attractants (chemotaxis) to other
inflammatory cells
- 3. Growth factors are the cause of fibroblast
proliferation, collagen deposition, and angiogenesis.
 Chronic Inflammation pathogenesis
B- The mediators :
• With chronic inflammation, the tissue degeneration is
normally mediated by nitrogen species, proteases, and
other reactive oxygen species released from
infiltrating inflammatory cells.
• Certainly, some damaging effects of these mediators
are thought to have main role in some diseases e.g.
genomic alterations in p53 were approved as causes
for many chronic inflammatory diseases (e.g.,
inflammatory bowel diseases and rheumatoid
arthritis) in addition to some cancers
 Chronic Inflammation pathogenesis
B- The mediators :
• Some cytokines (e.g., IFN-γ) secreted by
sensitized T lymphocytes and NK cells, bacterial
endotoxins, and other chemical mediators help in
recruitment and activation of macrophages.
• Certain cytokines and oxidized lipids (migration
inhibiting factors) can cause immobilization of
macrophages.
 Chronic Inflammation pathogenesis
• With chronic inflammation, healing process occurs
by fibrosis through fibroblasts in the granulation
tissue and in the surrounding tissue, both of which
are surrounding the damaged area and trying to
replace it to achieve repair.
• These ongoing simultaneous tissue degeneration
and fibrosis result in chronic inflammation
morphological picture.
 Lymphatic drainage
• Lymphatic vessels help to drain edema fluid
from extravascular space and transport the
leucocytes and cell debris.

• Lymphangitis (inflamed lymphatics)

• Lymphadenitis (inflamed LN)
Chronic Inflammation morphology
Macroscopic picture: variable e.g.:
- Fibrosis
- Chronic abscess
- Persistent sinus or fistula
- Ulcer
- Granuloma
 Chronic Inflammation
• Macroscopic appearances of chronic inflammation
- Fbrosis and thickening of the wall of a hollow viscus
by fibrous tissue in the presence of a chronic
inflammatory cell infiltrate. Fibrosis may become
the most prominent feature of the chronic
inflammatory reaction when most of the chronic
inflammatory cell infiltrate has subsided.
- Fibrosis is commonly seen in chronic cholecystitis,
'hour-glass contracture' of the stomach, where
fibrosis distorts the gastric wall and may even lead
to acquired pyloric stenosis, and in the strictures
which characterise Crohn's disease.
Stomach : Hour-glass contracture
 Chronic Inflammation morphology
• Macroscopic appearances of chronic inflammation
- Chronic ulcer, such as a chronic peptic ulcer of the
stomach with breach of the mucosa, a base lined by
granulation tissue and with fibrous tissue extending
through the muscle layers of the wall
- Chronic abscess cavity, for example osteomyelitis,
empyema thoracis.
- Chronic persistent sinus or fistula
Peptic Ulcer Disease
 Chronic Inflammation
• Macroscopic appearances of chronic inflammation
- granulomatous inflammation, perhaps with caseous
necrosis as in chronic fibrocaseous tuberculosis of
the lung
Tuberculous granuloma: gross

Lung-Tuberculosis
 Chronic Inflammation morphology
Microscopic picture
1. Infiltration by mononuclear cells such as
macrophages, lymphocytes, plasma cells, and
features of damaged tissue
2. Proliferation of fibroblasts with laying down of
collagen (due to effects of growth factors released by
platelet, macrophage, lymphocytes)
3. Proliferation of blood vessels (growth factor –
macrophage)
 Notice : (2+3 = granulation tissue formation)
4. In granulomatous inflammation caseating or non-
caseating granulomas are found
Morphological Features of Chronic
Inflammation

LYMPHOCYTE
“MONO”CYTE, MACROPHAGE
HISTIOCYTE, APC
*(MONOMORPHONUCLEAR CELLS)
 Macrophage

• Inactive monocytes hit by chemical mediators become

macrophages
• The main type of cells found in chronic inflammation
• Secretes ≥ 16 active products
• Accumulate via recruitment, local proliferation,
immobilization
• Variable appearance: epithelioid, giant, etc…
 Lung chronic inflammation

Lung acute inflammation

 Chronic Inflammation morphology
• Morphological microscopic types
(appearances) of chronic inflammation:
there are two types :
1- Non-specific (non-granulomatous
inflammation.
2- granulomatous inflammation.
 Chronic inflammation patterns
Chronic non specific
inflammation
• Features of chronic
inflammation e.g.:
– Some injurious chemicals or
infectious agents e.g chronic
hepatitis.
– Example: Auto-immune diseases,
e.g. auto-immune thyroiditis
Chronic granulomatous
inflammation
• Chronic inflammation in which
modified macrophages (epithelioid
cells) accumulate in small clusters
surrounded by lymphocytes. The small
clusters are called:
(GRANULOMAS)
• Example: Tuberculosis
 Non-specific Chronic Inflammation
• Also known as Non-granulomatous chronic
inflammation.
• This type is characterized by infiltration of
macrophages, lymphocytes and plasma cells in the
site of injury, but without forming granuloma.
Also fibrosis (repair process) and necrosis (tissue
damage) are seen. e.g. chronic viral hepatitis,
chronic cholecystitis, chronic osteomyelitis, etc…
Chronic Cholecystitis
Chronic Osteomyelitis
THANKS