Review Inflamasi

Djumadi Achmad
 Causes of Inflammation :

 Physical agents – Trauma, radiation

 Infection – microbial agents
 Chemicals – acid, alkali, toxins
 Ischemia / Infarction – necrotic tissue
 Foreign bodies - exogen/endogen
 Immune reaction - hypersensitivity
 Cardinal Signs of Acute Inflammation

• Calor : Warm – Hyperaemia.

• Rubor : Redness – Hyperaemia.
• Dolor : Pain – Nerve, Chemical med.
• Tumor : Swelling – Exudation
• Functio laesa: Loss of function - (Virchow 1902)
 Acute Inflammation
• Immediate and early response to tissue injury
(physical, chemical, microbiologic, etc.)
– Vasodilation
– Vascular leakage and edema
– Leukocyte emigration (mostly PMNs)
Vascular Leakage
Vascular Leakage
Cellular Event (margination, rolling, adhesion,
migration, phagocytosis & killing)
Leukocyte Activation and Removal of Offending Agents

• Leukocytes can eliminate microbes and dead cells by

phagocytosis, followed by their destruction in
phagolysosomes.
• Destruction is caused by free radicals (ROS, NO) generated in
activated leukocytes and lysosomal enzymes.
• Neutrophils can extrude their nuclear contents to form
extracellular nets that trap and destroy microbes.
(Neutrophil Extracellular Traps)
Leukocyte Activation and Removal of Offending Agents

• Enzymes and ROS may be released into the extracellular

environment.
• The mechanisms that function to eliminate microbes and
dead cells are also capable of damaging normal tissues (the
pathologic consequences of inflammation).
• Antiinflammatory mediators terminate the acute
inflammatory reaction when it is no longer needed.
Mediators of Inflammation
Figure 2-15 Interrelationships between the four plasma mediator systems triggered
by activation of factor XII (Hageman factor)..
 Termination of the Acute Inflammatory
Response
• Inflammation after the offending agents are removed.
Mediators of inflammation have short half-lives, and are
degraded after their release
• Neutrophils will die by apoptosis within a few hours after
leaving the blood
• Switch in the type of AA metabolite produced, from
proinflammatory leukotrienes to antiinflammatory lipoxins
• Liberation of antiinflammatory cytokines, including TGFbeta
and IL-10, from macrophages and other cells
 Causes of Chronic Inflammation
• Unresolved acute phase
• Persistent injury or infection (ulcer, TB)
• Prolonged toxic agent exposure (silica  silicosis ;
lipid  atherosclerosis
• Inappropriate immune reaction : allergic diseases,
autoimmune diseases (RA, SLE)

 Underlying pathogenesis of certain diseases such as

Alzheimer disease, metabolic syndrome, type 2
diabetes, and cancer
 Features of Acute and Chronic Inflammation

Feature Acute Chronic

Onset Fast: minutes or hours Slow: days
Cellular infiltrate Mainly neutrophils Monocytes/macrophages
and lymphocytes
Tissue injury, fibrosis Usually mild and self - Often severe and
limited progressive

Local and Prominent Less

systemic signs
Acute inflammation. Densely packed
polymorphonuclear leukocytes (PMNs)
with multilobed nuclei.
Chronic inflammation. Lymphocytes ,
plasma cells, and macrophages .
 Several functions of macrophages :

• Macrophages ingest and eliminate microbes and dead tissues.

• Macrophages initiate the process of tissue repair and are
involved in scar formation and fibrosis.
• Macrophages secrete mediators of inflammation, such as
cytokines (TNF, IL-1,chemokines, others) and eicosanoids.
• Macrophages display antigens to T lymphocytes and respond
to signals from T cells (feedback loop)  essential for defense
against many microbes by cell-mediated immune reponses.
Macrophage activation
 T and B Lymphocytes

• Antigen-activated (via macrophages and dendritic

cells)  effector and memory cells
• Release macrophage-activating cytokines (in turn,
macrophages release lymphocyte-activating
cytokines until inflammatory stimulus is removed)
Macrophage-lymphocyte interactions in chronic
inflammation
 Plasma Cells
• Terminally differentiated B cells
• Produce antibodies
 Eosinophils
• Found especially at sites of parasitic infection, or at
allergic (IgE-mediated) sites
 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
 Figure 2-20 Purulent inflammation. A, Multiple bacterial abscesses in the lung, in a
case of bronchopneumonia. B, The abscess contains neutrophils and cellular debris,
and is surrounded by congested blood vessels.
 Granulomatous Inflammation
• Granulomatous inflammation is a form of chronic
inflammation characterized by collections of activated
macrophages, often with T lymphocytes, and sometimes
associated with central necrosis.
• 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
Foreign Body Granulomas

• Chronic inflammatory response to inert

particles: uric acid crystals (Gout), talc,
sutures, and asbestos; produces a
"noncaseous” epithelioid granuloma, or
a "hard” granuloma” (non necrotic core)
• Absence ofT cell-mediated immune
responses

Foreign body giant cell

 Immune granulomas
• Caused by agents that inducing a persistent T cell-
mediated immune response
• The agent is difficult to eradicate, such as a persistent
microbe or a self antigen
• Macrophages activate T cells to produce cytokines,
– IL-2  activate other T cells
– IFNγ  activate macrophages
– IL-4 or IFNγ  transform the macrophages into epithelioid
cells and multinucleate giant cells
• Usually with central necrotic area (soft granuloma)
 Immune granulomas

Typical tuberculous granuloma showing an area of central necrosis

surrounded by multiple Langhans-type giant cells, epithelioid cells, and
lymphocytes.
 Systemic Effects of Inflammation
• The cytokines TNF, IL-1, and IL-6 are important mediators of
the acute-phase reaction; other cytokines, notably type I
interferon, also contribute to the reaction.
• The acute-phase response consists of several clinical and
pathologic change :
o Fever
o Acute-phase proteins
o Leukocytosis
o Other manifestation of the acute-phase response
o Sepsis
 Tissue Repair
• Tissue repair (healing) refers to the restoration of
tissue architecture and function after an injury
• Repair of damaged tissues occurs by two types of
reactions:
– regeneration by proliferation of uninjured cells and
maturation of tissue stem cells
– deposition of connective tissue to form a scar
 Cell and Tissue Regeneration
• The ability of tissues to repair themselves is
determined, in part, by their intrinsic proliferative
capacity.
• Based on this criterion, the tissues of the body are
divided into three groups.
 Labile Tissue : continuously dividing

• Hematopoietic cells in the bone marrow

• Surface epithelia :
– Stratified squamous epithelia of the skin, oral cavity,
vagina, and cervix;
– Cuboidal epithelia of the exocrine glands (e.g salivary
glands, pancreas, biliary tract)
– Columnar epithelium of the gastrointestinal tract,
uterus, and fallopian tubes;
– Transitional epithelium of the urinary tract.
 Stable tissues

• The parenchyma of most solid tissues, such as liver,

kidney, and pancreas
• Endothelial cells, fibroblasts, and smooth muscle
cells
• The proliferation of these cells is particularly
important in wound healing
• With the exception of liver, stable tissues have a
limited capacity to regenerate after injury
 Permanent Tissue

• The cells of these tissues are considered to be

terminally differentiated and nonproliferative in
postnatal life.
• The majority of neurons and cardiac muscle cells
belong to this category
• Thus, injury to the brain or heart is irreversible and
results in a scar, because neurons and cardiac
myocytes cannot regenerate
 Cell proliferation
• Cell proliferation is driven by signals provided by
growth factors and from the extracellular matrix.
• All growth factors activate signaling pathways that
ultimately induce the production of protein that are
involved in driving cells through the cell cycle and
other proteins that release blocks on the cell cycle
 Mechanisms of Tissue regeneration
• In labile tissues, such as epithelia of the intestinal
tract and skin,injured cells are rapidly replaced by
proliferation of residual cells and differentiation of
tissue stem cells, provided the underlying basement
membrane is intact
• In stable tissues regeneration is usually a limited
process (exception of the liver). Pancreas,adrenal,
thyroid, and lung have some regenerative capacity.
 Repair by Connective Tissue Deposition

• If repair cannot be accomplished by regeneration

alone it occurs by replacement of the injured cells
with connective tissue, leading to the formation of a
scar, or by a combination of regeneration of some
residual cells and scar formation
• In contrast to regeneration, which involves the
restitution of tissue components, scar formation is a
response that “ patches” rather than restores the
tissue
 Angiogenesis
• Angiogenesis involves sprouting of new vessels from existing
ones, and consists of the following steps :
– Vasodilatation in response to nitric oxide and increased
permeability induced by vascular endothelial growth
factor(VEGF).
– Separation of pericytes from the abluminal surface and
breakdown of the basement membrane to allow formation of a
vessel sprout.
– Migration of endothelial cells toward the area of tissue injury.
– Proliferation of endothelial cells just behind the leading
front(‘tip’)of migrating cells.
 Factors That Influence Tissue Repair

• Infection is clinically one of the most important

causes of delay in healing;it prolong inflammation
and potentially increase the local tissue injury.
• Diabetes is a metabolic disease that compromises
tissue repair for many reasons(chapter 24),and is one
of the most important systemic causes of abnormal
wound healing.
 Factors That Influence Tissue Repair

• Nutritional status has profound effects on

repair;protein deficiency,for example,and particularly
vitamin C deficiency, inhibits collagen synthesis and
retard healing.
• Glucocorticoid (steroid) have well-documented anti
inflammatory effects,and their administration may
result in weakness of the scar due to inhibition of
TGF-beta production and diminished fibrosis.
 Factors That Influence Tissue Repair

• Mechanical factors such as increased local pressure

or torsion may cause wounds to pull apart,or
dehisce.
• Poor perfusion,due either to arteriosclerosis and
diabetes or to obstructed venous drainage(e.g in
varicose veins), also impairs healing.
• Foreign bodies such as fragments of steel,glass,or
even bone , impede healing.
 Abnormalities in Tissue Repair
• Inadequate formation of granulation tissue or
formation of a scar can lead to two types of
complications: wound dehiscence and ulceration.
• Dehiscence or rupture of a wound, occurs most
frequently after abdominal surgery and is due to
increased abdominal pressure. Vomiting,coughing or
ileus can generate mechanical stress on the
abdominal wound.
Gastric ulcer
• An erosion which
extends down past
the muscularis
mucosa is an ulcer

• This slide shows in

lining of the stomach
with two punched
out areas
Foot ulcer
 Abnormalities in Tissue Repair
• Wound can ulcerate because of inadequate
vascularization during healing.
• Non healing wounds also form in areas devoid of
sensation. These neuropathic ulcers are occasionally
seen in patients with diabetic peripheral neuropathy
 Abnormalities in Tissue Repair
• Excessive formation of the components of the repair
process can give rise to hypertrophic scars and
keloids.
• Hypertrophic scars generally develop after thermal
or traumatic injury that involves the deep layers of
the dermis.
• Keloid formation seem s to be an individual
predisposition
 Abnormalities in Tissue Repair
• Contraction in the size of a wound is an important
part of the normal healing process. An exaggeration
of this process gives rise to contracture and results in
deformities of the wound and the surrounding
tissues.
• Contracture are particularly prone the develop on
the palms,the soles,and the anterior aspect of the
thorax, after serious burns and can compromise the
movement of joints.
Keloid
• hypertrophic scarring
• an over abundant
deposition of Type III
collagen
• genetic predisposition
is more common in
blacks
 Fibrotic disorders
• Fibrotic disorders include diverse chronic and
debilitating diseases such as
– liver cirrhosis,
– systemic sclerosis(scleroderma),
– fibrosing disease of the lung
• idiopathic pulmonary fibrosis,
• pneumoconioses,
• drug/radiation induced pulmonary fibrosis,
– end-stage kidney disease,
– constrictive pericarditis.