‫‪Professor Emeritus Dr.

SABAH AHMED ABU SABE‬‬

‫‪M.B.Ch.B.; Ph.D.; L.S.‬‬
‫‪Ex. Dean of faculty of Medicine, Kufa University‬‬
‫السأتاذ المتمرس الدكتور ‪:‬صباح أحمد أبو صيبع‬
‫عميد كلية طب الكوفه ورئيس فرع المأراض سأابقا ا‬
‫بروفسور في كلية طب بغداد سأابقا‬
‫شهادة الدكتوراة وشهادةمأابعد الدكتوراة‬

‫‪INFLAMMATION‬‬
 Inflammation
Inflammation is the physiological response of living tissue to injury.
Types of inflammation
1. Acute inflammation.
2. Chronic inflammation.
3. Subacute inflammation.

Acute inflammation
The irritant is usually moderate and of rapid action and is characterized by the
presence of polymorphonuclear leucocytes and fibrin and it is of short duration.
The major local manifestations of acute inflammation:
1. vascular dilatation (causing erythema or red and warmth or heat)
2. extravasation of plasma fluid and proteins (edema or swelling)
3. leukocyte emigration and accumulation in the site of injury

Vascular changes:
I. Changes in blood flow & caliber
●Transient vasoconstriction of the arterioles. The mechanism is unknown; it
may be neurogenic due to axonal reflex.
●Persistent vasodilatation, involves the arterioles. The blood flow thus will be
increased in the injured area & the volume of blood there will be 10 folds the
normal level. This is called active hyperemia,. This is the cause of heat & redness
observed clinically. This stage of increased blood flow will last for 10 to 15minutes
and is caused by chemical mediators e.g. histamine, 5HT etc; these are liberated
by tissue damage
●This is followed by slowing of blood flow which result from:
a. Increased permeability of microcirculation with escape of fluids into the
extravascular spaces.
b. Increase of the cellular component in the intravascular compartment.
The above changes (a and b) cause an increase in blood viscosity.
II. Changes in vascular permeability
Once vasodilatation starts, plasma proteins, which include fibrinogen, will pass
through the gaps between endothelial cells.

The cellular response

Normal blood flow is characterized by axial flow in which the plasma is seen near
the vessel wall & the cellular components (RBCs, WBCs and platelets) occupy the
central column.
In case of acute inflammation, the red cells & more importantly WBCs, will become
more closely packed near vessel wall especially in venules. This is called
margination or pavementing of leucocytes. Some of the leucocytes may pass
through the vessel wall & migrate into the extravascular spaces of the inflamed
area.This is called emigration of leucocytes.
Emigration
This is a process by which mobile WBCs escape from blood vessels into the
perivascular spaces & tissues. This may involve polymorphonuclear neutrophils
eosinophils, basophils, lymphocytes & monocytes. They pass by their amoeboid
movement into the endothelial junctions.
Chemotaxis
This refers to the directional movement of cells towards an attractant or,
locomotion oriented along a chemical gradient at the site of injury.
Chemotactic agents include:
1. Exogenous & endogenous substances such as soluble bacterial products,
2. Components of the complement system such as C5a.
3. Products of lipoxygenase pathway of arachidonic acid metabolism,
particularly leukotriene B4 (LTB4).
4. Cytokines as interleukin-8(IL-8).
Phagocytosis
Phagocytosis & release of lysosomal enzymes are two of the major benefits occurring
from the accumulation leukocytes at the site of inflammation.
There are three distinct steps in phagocytosis
1. Recognition
2. Attachment
3. Engulfment
Engulfment
Pseudopodes from leukocytes (cytoplasmic extensions) flow around the object to be
engulfed to form a membrane-bound phagocytic vacuole that contains the particle.
This will fuse with membrane-bound lysosomes to form phagolysosome.
Killing or degradation of the ingested material
This is achieved by the production of reactive oxygen metabolites such as
superoxide & hydrogen peroxide, which kill bacteria that become degraded by the
lysosomal enzyme hydrolase.
Chemical mediators
These are divided into three categories
I. Mediators that are derived from plasma (systemic mediators);
- The kinin-system
- The complement system C3a, C3b, C5b
- The coagulation & fibrinolyitc systems
II. Mediators released from cells
 Preformed mediators in secretory granules

- Histamines,Serotonin, Lysosomal enzymes

 Newly synthesized mediators

prostaglandins (PG), leukotrienes (LT), platelets-activating factor,

cytokines (such as lymphokines secreted by T lymphocytes).
Effects of inflammation
1. Beneficial effects; these act through the flow of exudates into the
inflammatory tissue & by the phagocytic & microbicidal effects of migrated WBCs.
a. Dilution of toxins:
Exudates dilute chemical & bacterial toxins.
b. Protective antibodies
These antibodies attack injurious agents and destroy them immunologically.
c. Fibrin formation
A network of the deposited fibrin is seen in the inflamed tissue forming a mechanical
barrier that precludes the movement & spread of bacteria.
d. Promotion of immunity:
Bacteria in the inflammatory exudates, whether free or phagocytosed, are carried to
the lymph nodes by lymphatics. There they mount an immune response, which
provides antibodies & cellular mechanisms that may appear after few days and
remain for years. These immunological mechanisms help destroy microbial agents.
e. Cell nutrition
Flow of inflammatory exudate brings in oxygen & glucose to the cells within the area
of inflammation. It also carries away the cellular waste products.

2. Harmful effects:
a. Swelling of acutely inflamed tissue may have serious mechanical effects e.g. acute
laryngitis cause suffocation in children.
b. Rise in tissue pressure
Inflammation when is confined within a restricted space cannot expand. The result is
an increase in tissue pressure & this interferes with cell function & blood flow. The
latter leads to ischemic injury e.g. encephalitis & meningitis both cause increased
intracranial pressure & death. Similarly osteomyelitis leads to bone necrosis.

c. Sever allergic reaction e.g. to pollens may cause asthma, dyspnoea.

Patterns of inflammation
1. Serous inflammation
This is characterized by outpouring of thin fluid that is either derived from the blood
(serum) or secretions of serous mesothelial cells of pleura, peritoneum, and
pericardium or joints spaces. Serous inflammation is seen for example in
tuberculous pleurisy.
2. Fibrinous inflammation
In this type there is exudation of large amounts of plasma proteins including
fibrinogen with subsequent precipitation of masses of fibrin e.g. fibrinous
pericarditis. 3. Suppurative inflammation:
This is characterized by the production of large amounts of pus or (purulent
exudates).
Abscess is a localized collection of pus caused by suppurative inflammation.The
central part consists of acidophilic debris ( dead tissue cells and dead WBCs) and this
is surrounded by viable neutrophils, which is surrounded by granulation tissue.
Ulcer is a discontinuity of epithelial surface (skin and mucouse membranes) .
4. Membranous inflammation (pseudomembranous inflammation):
This is a form of inflammatory reaction that is characterized by the formation of a
pseudomembrane e.g. diphtheria.
5. Catarrhal inflammation:
This is a mild inflammation of mucosal membranes as is seen in common cold,
bacillary dysentery, and food poisoning.

Fate of acute inflammation

1. Resolution: this means complete restoration of the injured area to normal.
2. Healing by fibrosis:
Fibrosis & scar formation.
3. Progression of acute inflammation to chronic inflammation.
4. Suppuration. Formation of pus is a common sequel of acute inflammation.

Chronic inflammation
This is an inflammation of slow progress and so of long duration & is marked chiefly
by the formation of new connective tissue. It may be a continuation of an acute
inflammation or it is chronic from the beginning by:
1. Injury e.g. physical or chemical, examples include response to talc powder (in
surgical operations) or asbestos or silica particles (in the lung).
2.Poor local circulation e.g. in association with varicose veins.
3Certain microorganisms cause chronic rather than acute inflammation e.g.
leprosy, T.B, or syphilis.
4.Autoimmune diseases e.g. rheumatoid arthritis .
5.Crohn’s disease a granulomatous disease affecting the GIT.

Morphological features of chronic inflammation

Chronic inflammation is of prolonged duration; it lasts for weeks, months or years, in
which active inflammation, tissue injury & healing proceed simultaneously.
Infiltration with mononuclear cells (chronic inflammatory cells) including

lymphocytes, macrophages & plasma cells.

 Tissue destruction largely induced by the inflammatory cells.

 Repair involving new vessel proliferation (angiogenesis) & fibrosis.

Chronic inflammatory cells

Macrophages migrate within the first 24 to 48 hr.
Activation of macrophages occurs through the effects of
1. Cytokines secreted by sensitized T-lymphocytes especially interferon γ
(INF- γ )
2. Bacterial endotoxin
3. Various chemical mediators.
After activation, macrophages secrete:
1. Acid & neutral proteases, causing tissue damage.
2. Toxic oxygen metabolites.
3. Neutrophil chemotactic factors.
4. Coagulation factors.
5. Arachidonic acid metabolites causing tissue injury.
6. Growth factors like fibroblasts growth factor (FGF), tumor necrosis
factor β (TNF β)
7. Angiogenic cytokines.
8. Collagenase.

Granulomatous inflammation
This is a distinctive pattern of chronic inflammation characterized by aggregation of
activated macrophages that have been modified by acquiring an enlarged squamous
cell-like appearance. These cells are called epithelioid cells.
Granulomas, the morphologic units of granulomatous inflammation; they are small
(0.5 mm to 2 mm) collections of epithelioid cells usually surrounded by a rim of
lymphocytes and sometimes fibroblasts.
The epithelioid cell may fuse to form multinucleated giant cells. Multinucleated giant
cells may or may not be present in granulomas and thus are not essential for the
diagnosis of granulomatous inflammation.
Multinucleated giant cells may achieve diameters of 40 to 50 microns and may
contain as many as 50 nuclei.
There are two morphological variants of multinucleated giant cells depending on the
distribution of their nuclei
1. Langhans’-type giant cells where the nuclei are arranged around the
periphery (creating a horse-shoe pattern).
 2. Foreign body-type giant cells where the nuclei are scattered
haphazardly. The foreign body-type cells are so named because they are
formed in the presence of larger amounts of indigestible material (foreign
bodies).
Causes of granulomatous inflammation include
1. Tuberculosis
2. Sarcoidosis
3. Deep fungal infections
4. Reactions to FB
5. Brucellosis (Malta fever)
6. Schistosomiasis (Bilharziasis)
7. Cat-scratch disease
8. Syphilis
9. Leprosy
TB is the most common cause of granulomatous inflammation. The granulomas of
TB are characterized by caseation necrosis.
Another common cause of granulomatous inflammation is that induced by the
presence of foreign bodies.
Foreign bodies that may trigger such granulomatous inflammation include suture
material, talc powder, undigested food material in anal fistulae etc.
These foreign bodies can be high-lightened by the use of polarizing lenses that cause
them to appear refractive.
Sarcoidosis is a systemic granulomatous disease of unknown etiology. Common
sites of involvement are lymph nodes (in particular mediastinal), lungs etc.
The granulomas are different from those caused by TB in that they are noncaseating.
They may also contain nonspecific structures such as the Schaumann bodies.
Other important granulomatous diseases include
- Tuberculous epididymitis.
- Tuberculous endometritis.
- Tuberculous meningitis.
- Crohn’s disease.
- Schistosomiasis (Bilharziasis) urinary bladder.