1.
Introduction
An important characteristic of living tissues is their
ability to respond to injury & this determines their
survival. Without an appropriate response the
tissue will be overwhelmed by external and internal
insults.
This response of body is referred to as
inflammation and is shown by all tissues of body.
Denoted by suffix “itis”, e.g. cellulitis, rhinitis,
appendicitis, osteomyelitis, laryngitis etc.
2. Inflammation
Definition – Inflammation (from Latin: meaning to burn) is
part of the complex biological response of body tissues to
harmful stimuli, such as pathogens, damaged cells, or
irritants, and is a protective response involving immune
cells, blood vessels, and molecular mediators.
Functions of inflammation are :
1. To localize & eliminate the initial cause of cell injury,
2. To clear out necrotic cells and tissues damaged from the
original insult and the inflammatory process, and
3. To initiate tissue repair.
Protective response, but potentially harmful.
3. Etiology
1. Exogenous causes:
A. Physical causes: i. Mechanical agents: injuries,
foreign bodies like splinters
ii. Thermal agents: burns, freezing
iii. Radiation injury
B. Chemical agents: toxic gases, acids, bases,
alcohols etc.
C. Biological agents: infections (by bacteria, viruses,
parasites), hypersensitivity reactions
Etiology contd..
2. Endogenous causes:
A. Circulation disorders: thrombosis, infarction,
hemorrhage
B. Autoimmune disorders
C. Enzymes activation – e.g. acute pancreatitis
D. Metabolic disorders – e.g. Gout
4. Classification
A. Acute inflammation – Acute inflammation
is an immediate and early response to an
injurious agent and it is relatively of short
duration, lasting for minutes, several hours or
few days.
It is characterized by exudation of fluids and
plasma proteins and the emigration of
leucocytes (predominantly neutrophils) to the
site of injury.
Classification contd…
B. Chronic inflammation – Chronic
inflammation is a prolonged inflammatory
process (weeks or months) where an active
inflammation, tissue destruction and attempts
to repair are proceeding simultaneously.
There is a progressive shift in the type of WBCs
at the site of inflammation, to mononuclear
cells.
A. Acute Inflammation
Events of acute inflammation are categorized
into vascular & cellular responses.
1) Vascular response has the following stages:
a) Phase I = Immediate (momentary)
vasoconstriction in seconds due to neurogenic or
chemical stimuli.
b) Phase II = Persistent progressive vasodilatation
of arterioles and venules resulting in increased
blood flow which causes redness (rubor) and heat
(calor).
c) Phase III = Increased vascular permeability
causes oozing of protein-rich fluid into
extravascular tissues leading to edema
(tumor). Due to this, the blood vessels are now
packed with red blood cells resulting in stasis.
This helps in localizing the spread of infectious
microorganisms.
Pain is due to stretching and release of
chemicals that stimulate nerve endings.
2) Cellular response – Movement of WBCs
(particularly granulocytes and monocytes) into
the area of injury.
The sequence of events are:
a) Margination, pavementing – WBCs begin to
marginate, or move to and along the periphery of
the blood vessels, virtually lining the endothelium
with time. This is called pavementing.
b) Emigration is a mechanism by which the
leukocytes pass through venules and capillary
walls and migrate into the tissue spaces.
c) Chemotaxis is a unidirectional attraction of
leukocytes from vascular channels towards the
site of inflammation within the tissue space
guided by secreted cytokines, bacterial and
cellular debris.
d) Phagocytosis – Neutrophils and macrophages
engulf and degrade the bacteria and cellular
debris.
Cardinal Signs (Local effects) of
Inflammation
Described by Celsus these are classically seen
in acute inflammation –
1. rubor (redness)
2. tumor (swelling)
3. calor (heat)
4. dolor (pain)
5. functio laesa, or loss of function was later
added by Greek physician Galen.
Systemic effects of Acute
Inflammation
Usually the inflammatory response remains confined to a
localized area. In some cases it can result in systemic
manifestations as mediators are released into the
circulation. These are -
1. Fever : The most important manifestation. It is
coordinated by the hypothalamus & cytokines (IL -1, IL-6,
TNF-α) released from macrophages etc.
2. Endocrine & metabolic: a) The liver secrets acute phase
proteins such as C-reactive protein & coagulation
proteins. CRP is raised in acute inflammation.
b) Glucocorticoids are increased, appetite is decreased.
3. Autonomic responses: a) Redirection of
blood flow from the cutaneous to the
deep vascular bed.
b) PR, BP, sweating.
4. Leucocytosis is a common, especially in bacterial
infections. Most bacterial infections induce neutrophilia.
Some viral infections cause lymphocytosis, parasitic
infestations & allergic reactions induce eosinophilia.
5. Leucopenia may be seen in typhoid fever and sepsis.
6. Weight loss is due to increased catabolism in skeletal
muscle, adipose tissue and the liver.
7. Behavioral effects: malaise, tiredness
B. Chronic Inflammation
Defined as a prolonged process in which tissue
destruction and inflammation occur at same time
Chronic inflammatory diseases are the most
significant cause of death in the world. WHO
ranks chronic diseases as the greatest threat to
human health.
Worldwide, 3 of 5 people die due to chronic
inflammation mediated diseases like stroke,
chronic respiratory diseases, heart disorders,
obesity, and diabetes.
Causes of Chronic inflammation
1.Sequelae of acute inflammation. E.g. osteomyelitis.
2.Recurrent attacks of acute inflammation e.g: cholecystitis
3.Exposure to low level of a particular irritant or foreign
material that cannot be eliminated by body - silica dust.
4.Failure of eliminating the infectious agent that can resist
host defenses and remain in body for prolonged period
e.g. Mycobacterium tuberculosis, protozoa, fungi etc.
5.Autoimmune disorders – body mounts immune response
against healthy tissue e.g. rheumatoid arthritis, SLE.
Types of Chronic Inflammation
1.Nonspecific proliferative: Characterized by
the presence of non-specific granulation tissue
formed by infiltration of mononuclear cells for
example chronic cholecystitis.
2. Granulomatous inflammation: A specific
type of chronic inflammation characterized by
the presence of distinct nodular lesions or
granulomas. There are two types:
a) Foreign body granuloma : Formed due to foreign
body or T-cell mediated immune response for
example silicosis, retained suture.
b) Infectious granuloma : Formed due to chronic
infection. Major causes include:
i) Bacterial: Tuberculosis, Leprosy, Syphilis,
Lymphogranuloma venerum.
ii) Fungal: Histoplasmosis, Cryptococcosis,
Coccidioidomycosis, Blastomycosis
iii) Helminthic: Schistosomiasis
iv) Protozoal: Leishmaniasis, Toxoplasmosis
Systemic effects of chronic
inflammation
1. Fever: Invariably there is mild fever, often with
loss of weight and weakness.
2. Anemia: Chronic inflammation is accompanied
by anemia of varying degree.
3. Leucocytosis: As in acute inflammation ,chronic
inflammation also has WBC but generally there
is relative lymphocytosis.
4. ESR: ESR is elevated in all cases of chronic
inflammation.
Symptoms of Chronic
Inflammation
1. Body pain, arthralgia, myalgia
2. Chronic fatigue and insomnia
3. Depression, anxiety and mood disorders
4. Gastrointestinal complications like constipation,
diarrhea, and acid reflux
5. Weight gain or weight loss
6. Frequent infections
Beneficial effects of inflammation
1. Dilution of toxins – Chemical and bacterial
toxins are reduced by dilution in the exudate &
carried in the venules and lymphatics.
2. Protective antibodies reach at the site of
inflammation & promote microbial
destruction. The complement, coagulation &
fibrinolytic systems are provided to the area.
3. Transport of drugs – Increase vascular
permeability - antibiotics circulate and reach
the site.
4. Fibrin formation – Traps microorganism and
aids phagocytosis.
5. Delivery of nutrients – to the cells / tissues at
the site of inflammation
6. Stimulation of immune response – By draining
into lymphatics, lymphocytes are exposed to
antigen which stimulates the immune
mechanism.
Harmful effects of inflammation
1. Tissue destruction: Inflammation may result in
tissue necrosis which may, in turn, incite further
inflammation.
2. Swelling: The swelling caused by inflammation may
have serious mechanical effects. Examples - acute
epiglottitis with interference in breathing; Acute
meningitis and encephalitis with effects of ICT.
3. Inappropriate response: The inflammatory reactions
seen in sepsis / SIRS , allergies (hypersensitivity)
represent severe manifestations of inflammation.
6. Treatment
1. Treat the cause – Identification and treatment of
cause is of prime importance because once the
cause is nullified, inflammation subsides by itself.
a. Infections – antibiotics / antiviral / antifungal etc.
b. Injury – rest to part
c. Abscess / dirty wound – drainage / debridement
d. Impacted foreign body – remove it
e. Hypersensitivity reaction – remove allergen,
antihistaminic drugs
2. Anti-inflammatory drugs –
a. NSAIDs – Inhibit COX mediated PG
synthesis at the site of injury / infection. They
are also potent analgesics & antipyretics. E.g.
Diclofenac, Ketorolac, Celecoxib etc.
b. Steroids – Irrespective of the cause, these
cover all components and stages of
inflammation but primarily they inhibit
recruitment of inflammatory cells and
production of inflammatory mediators. Topical
application used in chronic skin inflammations.
E.g. Dexamethasone, Prednisolone etc.
c. Enzyme preparations – Serratiopeptidase,
Trypsin, Chymotrypsin, Bromolein
preparations are being used but the data
regarding efficacy is lacking.
3.Cold/ hot fomentation – cold fomentation leads
to vasoconstriction, thereby decreasing edema
and pain (due to induced numbness). Used in
traumatic inflammation with marked edema.
- Hot fomentation helps in decreasing pain by
vasodilatation induced washout of pain mediators
and by soothing post-traumatic spasm and
muscle cramps. However, it can increase the
edema.
7. Course of acute inflammation
1. Resolution of normal structure and function of the tissue
e.g. in common infections, injuries etc.
2. Healing by fibrosis – Fibrous scarring occurs when there is
extensive damage to tissues or where regeneration is not
possible, forming a scar composed mainly of collagen. The
scar lacks any specialized structures, such as parenchymal
cells, hence functional impairment may occur.
3. Abscess formation – Seen in infections specially bacteria. A
cavity is formed containing pus, made of dead WBCs and
bacteria with general debris from destroyed cells.
4. Chronic inflammation
Resolution of inflammation
Defined as complete restoration of the
inflamed tissue back to a normal status.
The inflammatory response must be actively
terminated when no longer needed to prevent
unnecessary "bystander" damage to tissues.
Failure to do so results in chronic inflammation,
and cellular destruction.
There is rapid destruction of causal agent,
inflammatory measures such as vasodilation,
chemical production, and leukocyte infiltration
cease, and damaged cells regenerate. In
situations where limited or short lived
inflammation has occurred, this is usually the
outcome.
