INFLAMMATION Flashcards
OVERVIEW OF INFLAMMATION
• A host response to local injury in vascularized tissues to
infection & damaged tissues
• Brings cells and molecules of host defense from the circulation
to eliminate the offending agents
• Not in itself a disease, but is usually a manifestation of
disease.
• Terminates when offending agent is eliminate
Stimuli of Inflammation
- Infections (Bacterial, Viral, Fungal)
- Trauma (Blunt/Penetrating)
- Physical & Chemical agents (irradiation, burns, acids)
- Tissue necrosis
- Foreign bodies (Sutures)
- Immune reactions
Classification of Inflammation
• Classified into:
• Acute - the initial & often transient series of tissue reaction to
injury.
• Chronic – the subsequent & often prolonged tissue reactions
following the initial response.
• Characterized by differences in the cell types taking part in the
inflammatory response
ACUTE INFLAMMATION
• Initial, rapid response: infections/tissue damage
• Within minutes/hours
• Short duration: several hours/ few days
• Exudation of fluid & plasma proteins (oedema)
• Emigration of leukocytes (neutrophils)
• When it fails to clear the stimulus: progress to a protracted phase
of chronic inflammation (CI).
Chronic Inflammation
- It is of longer duration
- Associated with more tissue destruction
- Presence of lymphocytes and macrophages
- Proliferation of blood vessels
- Deposition of connective tissue
• A response of prolonged duration (weeks or months) in which
inflammation, tissue injury and attempts at repair coexist, in varying
combinations
• May precede AI
• Start insidiously as a low-grade, smoldering response
Cardinal Signs of Inflammation
- Rubor (Redness)
- Tumor ( Swelling)
- Calor (Heat)
- Dolor ( Pain)
- Functio laesa(Loss of function)
Components of Acute & Chronic Inflammation
• Major participants: blood vessels & leukocytes
• Blood vessels dilate: slow down blood flow & increase their
permeability
• Characteristics of the endothelium lining change: leukocytes migrate
into the tissues.
• Leukocytes are activated: Ingest & destroy microbes and dead cells
Sequence Of Events
• Recognition of offending agent by host
cells in extravascular tissue
• Recruitment of leukocytes and plasma
proteins into the tissues
• Removal of the stimulus for inflammation
• Regulation of the response
• Repair of damaged tissue
the acute inflammatory response involves:
a) Vascular changes
b) Cellular events (leukocytes)
Vascular changes
Vasodilation
• Induced by the action of several mediators:
histamine on vascular smooth muscle
• Earliest manifestations of AI
• First involves the arterioles and then leads to
opening of new capillary beds in the area.
• Increased blood flow: heat & redness
(erythema)
Increased permeability of the microvasculature
• Contraction of endothelial cells: increased
interendothelial spaces
• outpouring of protein-rich fluid : extravascular
tissues
STASIS IN VASCULAR CHANGES
• Slower blood flow, concentration of red cells in small vessels,
and increased viscosity of the blood.
• Engorgement of small vessels
• Vascular congestion & localized redness
• Neutrophils, accumulate along the vascular endothelium
• Endothelial cells are activated by mediators: express increased
levels of adhesion molecules
Characteristics of Leaked Fluid (Exudation)
• Escape of fluid, proteins and blood cells from blood into tissue or
body cavities exudation.
• An exudate is an extravascular fluid that has a high protein
concentration & contains cellular debris.
• A transudate is a fluid with low protein content, little or no
cellular material, and low specific gravity
• Oedema denotes an excess of fluid in the interstitial tissue or
serous cavities & can be an exudate or a transudate.
• Pus - a purulent exudate: leukocytes, dead cells & microbes
Characteristics of Oedema
Exudate
Specific gravity ≥1.020
Protein content High
Cells & debris High
cause by inflammatory
Transudate
Protein content low Cells & debris low specific gravity <1.020 caused by Inflammatory & Others
Cellular Events in Acute Inflammation
• Recruitment of Leukocytes to sites of infection and injury
1. In the lumen: margination, rolling, & adhesion to
endothelium.
2. Transmigration across the endothelium (diapedesis)
3. Migration in interstitial tissues toward a chemotactic
stimulus
mechanism of margination
White blood cells are confined to a central axial column of the vessel.
• Due to stasis hemodynamic conditions change, & more white cells assume a peripheral position along the endothelial surface
ROLLING AND ADHESION
- Leukocytes tumble slowly along the endothelium & adhere transiently (rolling),
- Finally coming to rest at some point where they adhere firmly (adhesion)
diapedesis
- Leukocytes insert pseudopods into the interendothelial junctions & squeeze through to assume a position between the endothelial cell & the basement membrane
- Traverse the basement membrane & escape into the extravascular space
Morphologic Patterns of Acute Inflammation
• Morphologic hallmarks - Dilation of small blood vessels & accumulation of
leukocytes and fluid in the extravascular tissue.
• Special morphologic patterns are often superimposed
- Severity of the reaction
- Specific cause
- Particular tissue and site involved
• Provide valuable clues about the underlying cause
Serous inflammation
Exudation of cell poor fluid into spaces created by cell injury or into body cavities lined
• Increased vascular permeability) or from the secretions of mesothelial cells
• Transudate e.g. Skin blister from a
burn
Fibrinous inflammation
- Vascular leaks are large/there is a local pro-coagulant stimulus (e.g. cancer cells)
- Fibrinogen leaks & Fibrin is formed
- Characteristic of inflammation lining body cavities e.g. pericardium• Lead to scarring - organisation
PURULENT (SUPPURATIVE) INFLAMMATION
• An exudate - neutrophils, liquefied debris of
necrotic cells, and edema fluid(pus).
• Bacterial infection (pyogenic)-staphylococci
• Produced by seeding of pyogenic bacteria
• Acute appendicitis
ULCERS
- A local defect of the surface of an organ
- Produced by the shedding of inflamed necrotic tissue.
- Peptic ulcer
- Chronic = Fibroblasts, scarring and inflammatory cells
Outcomes of Acute Inflammation
• Complete resolution - little tissue destruction & removal of
microbes
• Healing by scarring, or fibrosis in tissue incapable of
regeneration
• Chronic inflammation- persistence of agent or disturbance
in healing
Mediators of Inflammation
• Substances that initiate & regulate inflammatory reactions
• Most important are vasoactive amines, lipid products (prostaglandins
and leukotrienes), cytokines (including chemokines), and complement
activation.
• Either secreted by cells/generated from plasma proteins
• The major cell types are the sentinels that detect invaders and tissue
damage
• Plasma derived mediators produced in the liver
Causes of Chronic Inflammation
• Persistent infections e.g. Mycobacteria
• Hypersensitivity diseases - excessive activation of immune system/
unregulated immune responses against microbes or common
environmental substances
• Prolonged exposure to potentially toxic agents e.g. silicosis
• Sometimes takes specific pattern - granulomatous reaction
• Fibrosis may dominate the late stages
MORPHOLOGY OF CHRONIC INFLAMMATION
Infiltration with mononuclear cells; macrophages, lymphocytes & plasma cells • Tissue destruction • Attempts at healing by connective tissue replacement of damaged tissue (angiogenesis & fibrosis)
GRANULOMATOUS INFLAMMATION
Collections of activated macrophages(epithelioid cells)
• Epithelioid cells & multinucleated giant cells
• Foreign body granulomas (talc)
• Immune granulomas (cytokines e.g. IL2)
Morphology of Granulomatous Inflammation
• Aggregates of epithelioid macrophages are surrounded by a collar
of lymphocytes
• In Mycobacterium tuberculosis a combination of hypoxia and free
radical–mediated injury leads to a central zone of necrosis
• Grossly, this has a granular, cheesy appearance and is therefore
called caseous necrosis
• Microscopically, appears as amorphous, structureless, eosinophilic,
granular debris, with complete loss of cellular details
Differential of Granulomatous Inflammation
- Limited number of conditions that cause it (some life-threatening)
- TB granuloma, referred to as a tubercle
- Leprosy
- Syphilis
- Disease of Unknown aetiology - Sarcoidosis
- Crohn disease
Systemic Effects of Inflammation
• Inflammation is associated with cytokine-induced systemic
reactions that are collectively called the acute-phase response:
- Fever
- Acute-phase proteins (C-Reactive Protein)
- Leukocytosis
• Other: ↑ pulse &BP, shivering, chills, anorexia, somnolence, and
malaise, probably because of the actions of cytokines on brain
cells
fever
- An elevation by 1° to 4°C
- Substances that induce fever are called pyrogens
- Caused by prostaglandins: hypothalamus
- NSAIDs: inhibit prostaglandin synthesis
Acute phase proteins
• Mostly synthesized in the liver
• Plasma concentrations: Increase several hundred-fold
• Three of the best-known of these proteins are
- C-reactive protein (CRP)
- Fibrinogen
- Serum amyloid A (SAA) protein
Leukocytosis
• Leukocyte count ++ 15,000 /20,000 cells/mL > 100,000 cells/mL.
• Most bacterial infections = increase neutrophil count: neutrophilia
• Viral infections = increase in lymphocytes: lymphocytosis
• In some allergies and parasitic infestations = increase in
eosinophils: eosinophilia.
• Certain infections are associated with a decreased number of
circulating white cells leukopenia
Other Systemic effects of Inflammation
• Disseminated Intravascular Coagulation (DIC)
• Hypotensive shock
• Metabolic disturbances (including insulin resistance and
hyperglycemia
• This clinical triad is known as septic shock
