INFLAMMATION

A complex reaction to various injurious agents

Consists of vascular responses, migration and activation of leukocytes, and systemic
reactions
A protective response
Ultimate goal:
Remove initial cause of injury
Remove consequences of injury
Important in tissue repair
Destroy, dilute, wall of infectious process
Sets in motion tissue repair
Regeneration
Scarring
Unique features
Reaction of blood vessels
Accumulation of fluids and electrolytes in extravascular space
Tissues and cells are involved in this reaction
Fluid and plasma proteins, blood vessels, circulating cells (WBCs), CT cells (mast
cells, fibroblasts, macrophages), extracellular matrix (collagen, elastin), adhesive
glycoproteins
Inflammation is terminated when the inciting agent is eliminated and the mediators have
degenerated

Components of inflammatory response

1. Vascular reaction
Vasodilation
Increased permeability
2. Cellular reaction
Margination
Rolling
Adhesion
Transmigration
Migration

ACUTE INFLAMMATION
-

Predominating WBC: Neutrophils

A rapid response to an injurious agent that aims to rapidly bring mediators of
inflammation to the site of injury
Alterations in blood flow
Increased vascular permeability
Emigration, accumulation, and activation of neutrophils
Infiltration by polymorphonuclear cells (BEN)
Resolve in 1-2 wks.

Stimuli for acute inflammation

- Infections
- Trauma
- Physical and chemical agents
- Tissue necrosis
- Foreign bodies
- Immune rxns
Mediators of acute inflammation
- Vasoactive amines (histamine and serotonin)
- Kinins (Bradykinin)
- Complement system (C3a and C3a)
- Clotting system
1. Arachidonic acid metabolites: Prostaglandin, Prostacyclin, Thromboxane A2,
Leukotrienes (B4, C4, D4, E4)
2. Oxygen metabolites
3. Platelet aggregating factor
4. Nitric oxide
5. Cytokines (Interleukins, TNF)
Hallmark of Acute Inflammation:
- Increased vascular permeability
Edema
- Swelling due to tissue fluid accumulation
Exudation:
- Escape of fluid, proteins and blood cells from the vascular system into interstitial tissue
or body cavities
- Two types
Exudate
Transudate

Protein content
Sp Gr
Cellular components
Pus
-

Exudate
High
>1.020
Inflammatory cells, cellular
debris

Transudate
Low (Albumin)
<1.020
None

An exudate rich in inflammatory cells (leukocytes) and cellular debris

MORPHOLOGIC PATTERNS
1. Serous
- Plasma-like effusion with no cells
- There is abundant protein-rich fluid exudate with a relatively low cellular content
- Vascular dilatation may be apparent to the naked eye
- Inflammation of the serous cavities, such as peritonitis, and inflammation of a
synovial joint, acute synovitis
- Early inflammation, heart failure, pleural effusions
2. Purulent or Suppurative
- The term suppurative and purulent denote the production of pus
- Contains dying and degenerate neutrophils, proteins, tissue debris, infecting
organisms
- Caused by pyogenic bacteria
- The pus may become walled-off by granulation tissue or fibrous tissue or produce
an abscess (a localized collection of pus in a tissue
- Empyema

Hollow viscus fills with pus (empyema of the gall bladder or the appendix)

3. Fibrinous
- Contains large amounts of fibrinogen
- Forms thick stick meshwork that may cause areas to stick together
- Thick fibrin coating
- Often seen in acute pericarditis giving the parietal and visceral pericardium a bread
and butter appearance
4. Membranous
- Contains fibrinous or fibrinopurulent material with necrotic cells
- Often found in mucous membranes, some microbial infection
5. Serosanguinous
- Contains both serous and hemorrhagic materials
- Caused by bleeding, serous exudation like injury and burns
Exudates in Inflammatory Process
1. Hemorrhagic
- Contains large amount of RBC and other cells
- Damaged or vascular injury or permeable blood vessels or depletion of coagulation
factors
- Acute pancreatitis due to proteolytic destruction of vascular walls, and in
meningococcal septicemia due to disseminated intravascular coagulation
2. Mucinous or Catarrhal
- When mucus hypersecretion accompanies acute inflammation of a mucous
membrane
- Contains large amount of mucous and epithelial cells
- Inflammatory conditions like allergic rhinitis, common
Types of Inflammation According to Location
1. Abscess
- Localized collection of pus in a part of the body, surrounded by an inflamed area
- The area will most likely look like a giant boil or cyst that can become extremely
red and infected
2. Ulcer
- An open sore of the skin, eyes or mucous membrane, often caused by an initial
abrasion and generally maintained by an inflammation and/or an infection
3. Catarrhal
- Mucosal surface
- Thick mucous and WBCs
4. Membranous
- An epithelium becomes coated by fibrin, desquamated epithelial cells and
inflammatory cells
- An example is the grey membrane seen in pharyngitis laryngitis due to
Corynebacterium diphtheriae
5. Pseudomembranous
- Formed by the fibrin and necrotic surface epithelium
- A structure which resembles the luminal surface of tissue (looks like the affected
tissue is covered by a membrane)

Types of Inflammation According to Distribution/Location of Lesion in an Organ

1. Focal
- Single abnormality or inflamed area within a tissue
- Size varies from 1 mm to several cms in diameter
2. Multifocal
- Arising from or pertaining to many foci (several foci separated from one another)
- Size is variable
- Each focus of inflammation is separated from the other inflamed foci by an
intervening relatively normal zone of tissue
3. Locally Extensive
- Involvement of considerable area within an organ
- Also known as Focally Extensive
- Possible origin
o Several local reactions that spread into adjacent tissue
o Coalescence of foci in a multifocal reaction
4. Diffuse
- Involve all the tissue or organ in which the inflammation is present
- Variations in severity may exist
- Interstitial pneumonia
Outcome of Acute Inflammation
- Complete resolution
- Healing (by CT replacement or scarring)
- Abscess formation
- Progression to chronic inflammation
CHRONIC INFLAMMATION
-

Predominating WBC: Lymphocytes

An inflammation of prolonged duration
Infiltration by mononuclear cells (macrophages, lymphocytes, plasma cells)

Causes
1. Follows an acute inflammation
2. Repeated bouts of acute inflammation
A. Persistent infections of intracellular microbes (tubercle bacilli, viral infections)
B. Prolonged exposure to nondegradable but potentially harmful substances
(silicosis, asbestosis)
C. Immune reactions (autoimmune disease)
Hallmark of Chronic Inflammation:
- Mononuclear cells
Morphology
1. Infiltration of mononuclear cells (macrophages, lymphocytes, plasma cells, mast cells,
eosinophils)
2. Tissue destruction
3. Attempts at healing by CT replacement (angiogenesis and fibrosis)
Granulomatous Inflammation
-

A distinctive chronic inflammatory reaction in which the predominant cell type is an

activated macrophage with a modified epithelial-like (epithelioid) appearance. In the
focus of inflammation (granuloma), microscopic aggregations of macrophages are
transformed into epithelioid cells surrounded by collar of mononuclear leukocytes,
principally lymphocytes and occasional plasma cells. Such epithelioid cells often fuse to
form giant cells comprising of a large mass of cytoplasm with 20 or more small nuclei

arranged peripherally in a horseshoe shape (Langhan's Giant Cell) or haphazardly

(body-type).
Characterized by formation of granulomas
Granuloma
Focal aggregation of activated macrophages which are transformed in an
epithelial-like (epithelioid histiocytes) cells, have an abundant pink cytoplasm,
and are surrounded by numerous lymphocytes and plasma cells
Histiocytes
Surround foreign body
Multinucleated giant cells that try to eat the foreign body, no arrangement
Tuberculosis, leprosy, syphilis

Two types of granuloma

1. Foreign body granuloma
- Caused by inert foreign bodies
- Material (talc), sutures
- No inflammatory or immune reactions present
2. Immune granuloma
- Caused by immune T cell-mediated reactions
- Insoluble particles (microbial parts)
- Inflammatory reactions present
Resolution Inflammation (Healing)
Simple Resolution
- No destruction of normal tissue
- Offending agent is neutralized
- Vessels return to their normal permeability state
- Excess fluid is reabsorbed
- Clearance of mediators and inflammatory cells
Regeneration
- Replacement of lost or necrotic tissue with a new tissue that is structurally and
functionally similar to those that were destroyed
- The intact, healthy neighboring cells surrounding the dead cells will proliferate to
replace the affected cells
Replacement by a CT scar
- Formation of a new type of tissue that caused fibrous scar production with some
loss of tissue function
- Angiogenesis
- Migration and proliferation of fibroblasts (laying down collagen)
- Deposition of extracellular matrix
- Remodeling
- Reorganization of the fibrous tissue, contraction of wound edges
- Cicatrization
Formation of the mature scar
Cicatrix
o Scar
o Less vascular, pale, contracting scar tissue
- Epithelialization
Systemic Effects: Inflammation
- Fever, increase in pulse and BP, decreased in sweating, rigors, chills, anorexia,
somnolence, malaise, lymphadenopathy
- Increase plasma levels of acute phase proteins (CRP, serum amyloid A protein)
- Leukocytosis
- Sepsis
- Shock
Factors Modifying the Inflammatory-Reparative Response
- Adequacy of blood supply
- Nutritional status of patient
- Presence or absence of infection

Presence or absence of DM
Presence of absence of immunosuppressive drugs (e.g. glucocorticosteroids)
Adequate levels of circulating, normal functioning WBCs