Inflammation Flashcards
What is inflammation?
- A major component of the innate immune response whereby the immune system recognizes and removes harmful and foreign stimuli and begins the healing process
- Local response of tissues to injury with subsequent necrotic cell death due to any agent
- Complex reaction to injurious agents that consist of: Vascular response , Cellular reaction, Systemic reaction
Acute Inflammation
- lasts from seconds to 2-3 days
Sub-acute Inflammation
- 3-4 days up to ~2 weeks
Chronic Inflammation
- weeks to months
What is acute (exudative) inflammation?
- Immediate/rapid and early defensive response in the host tissue to injury
- Non-specific
Main characteristic feature: Exudate
- Inflammatory extravascular fluid/infiltrate
- Plasma liquid, plasma proteins, leukocytes, red blood cells, cellular debris & sometimes also of infective germs
- Specific gravity above 1.020 (normal range 1.010-1.020)
Changes in microcirculation
- Exudation of fluid
- Emigration of leukocytes
Inflammation Nomenclature: -itis. Examples:
- Appendicitis
- Cellulitis
- Meningitis
- Pneumonitis
- Nephritis
- Myocarditis
What are the cardinal signs of acute inflammation?
- Calor (Heat)
- Rubor (Redness)
- Tumor (Swelling)
- Dolor (Pain)
- Function Laesa (Loss of Function)
What are the three major components of acute inflammation pathogenesis?
- Vasodilation (blood flow)
- Increased vascular permeability (interstitial fluids/proteins)
- Process of Leukocyte Extravasation (blood stasis)
Describe vasodilation in the pathogenesis of acute inflammation
- Induced by several mediators (histamine, nitic oxide) on vascular smooth muscle
- Arteriolar vasodilation
- Increased blood flow (erythema ) - Clinical Signs: Rubor, Calor
Describe increased vascular permeability in the pathogenesis of acute inflammation
- Endothelial cells become “leaky“
- Exudation of protein-rich fluid into the interstitium
- Markedoutflowof fluid and accumulation in interstitial tissue (edema) -> tumor = swelling
- Loss of fluid and increased vessel diameter (Vascular stasis , Concentration of erythrocytes in small vessels) - Increased blood viscosity
- Impedes further outflow
- Clinical Signs: Rubor, Calor, Tumor
Describe leukocyte extravasion (blood stasis) in the pathogenesis of acute inflammation
- Blood stasis = Increased cells and plasma proteins
- Delivery of leukocytes (neutrophils) from the blood to the site of tissue injury
- Kill pathogens & remove necrotic tissue & foreign substances
Three steps:
- Margination
(Rolling
& Adhesion)
- Transmigration
- Migration
Describe the 3 steps of leukocyte extravasion (blood stasis)
- Leukocyte margination:
Leukocytes adhere to endothelial cells of the blood vessels
- binding due to cell adhesion molecules (CAMs)
Leukocyte rolling
- Selectins lightly tether neutrophils to endothelium -> begins rolling along the surface
Firm adhesion of Leukocytes
- Tighter binding occurs through the interaction of ICAMs on the endothelia cells with interns on the neutrophils
- Leukocyte Transmigration
- Diapedesis: movement across endothelial layer - Leukocyte migration:
- Chemotaxis -> migration toward a chemotactic stimuli (e.g. bacterial products, cytokines, complement proteins like C5)
- Activation and Phagocytosis
What is the wheal and flare inflammatory response (triple response)?
Type I allergic reaction
- Flare (Reddening (vasodilation))
- Wheal (swelling = fluid accumulation)
What are the outcomes of acute inflammation?
Complete resolution
Abscess formation
Fibrosis
- After substantial tissue destruction
- In tissues that do not regenerate
- After abundant fibrin exudation especially in serous cavities (pleura, peritoneum)
Progression to chronic inflammation
What are the 3 classes of body fluid based on composition?
- Transudate
- Exudate
- Edema (Oedema)
What is transudate?
- Fluid leaks out because of increased hydrostatic pressure or decreased osmotic pressure
- Ultrafiltrate of plasma with little protein and few or no cells
What is exudate?
- Extravascular fluid collection, rich in protein and cells
- In inflammation because vascular permeability increases
What is edema (oedema)?
- Excess extravascular fluid in interstitial space
- Either transudate or exudate
- Pus: Made up of neutrophils, necrotic cells and edema fluid
Effusions into body cavities can be further described as follows:
- Serous: transudate with mainly edema fluid and few cells
- Serosanguinous: effusion containing red blood cells
Describe the acute inflammation cycle
What are the morphological patterns of exudative (acute) inflammation?
- Serous Inflammation
- Fibrinous Inflammation
- Catarrhal Inflammation
- Purulent/Suppurative Inflammation
What is serous inflammation?
- Accumulation of excessive clear watery fluid with variable protein content
- Occur in skin and peritoneal, pleural and pericardial cavities
- Acute inflammatory exudate with a low plasma protein & cell content (transudate)
What is fibrinous inflammation?
- Fibrins formed in extracellular spaces
- Occur in membrane-lined cavities such as the pleura, pericardium and peritoneum
- Large amounts of fibrinogen pass the vessel wall
- Acute inflammatory exudate with high plasma protein content - Fibrinous Pericarditis
What is fibrinous pericarditis?
- Exudative inflammation
- Visceral pericardium infiltrated by fibrinous exudate - Exudate consists of fibrin strands and leukocytes
- Fibrin describes an eosinophilic network
- Myocardium has no changes
What is catarrhal inflammation?
- Inflammationof the mucous membranes
- Mainly in airways or cavities of the body e.g. throat & paranasal sinuses, trachea, intestines
- Enlargement of secretory epithelial cells & exudate of mucus and white blood cells -> swelling of mucous membranes
- Often due to an infection or allergy
What is purulent/suppurative inflammation?
- Caused by certain bacteria
- Production of large amounts of pus or purulent exudate consisting of neutrophils, necrotic cells, and edema fluid
- Circumscribed collection of pus can form an abscess
- Abscesses
- Purulent Exudate
What are abscesses?
- Localised collections of exudative purulent inflammatory tissue
- Defense reaction to bacteria -> abscess’ wall seals infected tissue from adjacent healthy cells
- Central region: mass of necrotic leukocytes and tissue cells with zone of neutrophils around
- Outside this region vascular dilation, parenchymal and fibroblastic proliferation
- In time abscess may become walled off and replaced by connective tissue
Image: A recent abscess in the white matter, consisting of pus
- Vessels present congestion and important perivascular edema
What is purulent exudate?
Describe persistent infections as a cause of chronic inflammation
- Tuberculosis
What is tuberculosis?
- Systemic infectious disease of worldwide prevalence - Chronic inflammation caused byMycobacterium tuberculosis
- Varying manifestations -> most affected organ is the lung
- Life threatening in individuals with compromised immune system
- Microscopically, the characteristic lesion in tuberculosis is the tuberculous granuloma areas with caseation necrosis, activated macrophages and lymphocytes, & giant cells (fused macrophages with multiple nuclei and large cytoplasm) -> a granuloma effectively “walls off” the offending agent
- Treatment against TB: antibiotics
Pulmonary Tuberculosis:
- Tuberculous granuloma localized in the pulmonary interstitium
- Surrounding alveoli compressed with parenchyma destruction
Describe prolonged exposure to toxic substances as a cause of chronic inflammation
Silicosis - inflammatory lung disease
- when Silica is inhaled for prolonged periods
Hyperlipidemia
- Cholesterol & triglycerides build up
- Atherosclerosis of arterial wall
What are lesions in chronic inflammation?
- Larger areas of the nervous system that have been inflamed or demyelinated
- Contain activated T cells, B cells, Macrophages and pro-inflammatory cytokines
- Early lesion: vein surrounded by inflammatory cells in the centre: mononuclear inflammatory cells
- Chronic lesion: vein in centre few mononuclear cells almost complete demyelination severe astrogliosis very little inflammation
Describe allergies as a cause of chronic inflammation
- Immediate Type I Hypersensitivity
- Inappropriate immune response triggering inflammation, vasodilation, and nerve irritation
- In sensitised host immediate reaction (minutes) after antigen (allergen) interacts with IgE bound to mast cells
- Examples: hay fever, asthma, anaphylaxis
Mast cell activation after IgE cross linking -> degranulation &release of mediators (histamine) -> inflammatory response:
- blood vessel dilation
- vascular leakage
- muscular spasm
- pro-inflammatory molecules
- cytokine release
- recruitment of leukocytes
Describe non-resolution (following acute inflammation) in chronic inflammation
E.g. Chronic leg ulcer:
- Affects ~ 1% of Australians
- Break in the skin of the leg allows air and bacteria to getinto underlying tissue
- Poor circulation – Venous Disease 80%, Arterial Disease 15%, other 5%
What are granulomas?
Granuloma: Small nodule of inflammation characteristic for chronic inflammation
- Collections of activated Macrophages, T lymphocytes and sometimes necrosis
- forms in an attempt to contain and remove a harmful agent from the body
histiocyte= morphological term for tissue-residentmacrophages
Describe foreign body (Non-Immune type) granulomas
- If particles are too large to be phagocytosed
- Material usually inert –> does not evoke immune response
- Endogenous: hair shafts, keratin, cholesterol - Exogenous materials: splinter, metal dust, talc, suture material, parasites, oil droplets, wood, metals, silica, silicon
Foreign body granuloma - to suture material:
- Due to suture material
- Multinucleated giant cells
- Giant cells are fused macrophages with haphazardly arranged nuclei
- Granulomas are non-necrotic
Describe immune granulomas and provide an example
- When immune cells clump together and create tiny nodules at the site of the infection or inflammation.
- A granuloma is the body’s way to contain an area of bacterial, viral or fungal infection so it can try to keep it from spreading, or to isolate irritants or foreign objects.
Cause: Insoluble particles capable of inducing a cell mediated immune response e.g. response to infection by mycobacterial & fungal organisms
- Usually non-degradable antigens
Unknown etiology granulomas - Crohn’s Disease:
- Chronic Granulomatous disorder
- Can involve any portion of the GIT including oral cavity
- Th1 disorder
- Non-caseating granulomatous inflammation in 50% of cases
- Clusters of neutrophils within crypts
Describe unspecific chronic inflammation
Chronic peptic ulcer:
- Cause:
destruction of gastric or duodenal mucosa, Helicobacter pylori infection
- Ulcerated surface: acute and chronic inflammatory cells
- Image: Inflammatory granulation tissue
- If erosions perforate wall, can lead to peritonitis and hemorrhage
- Fibrous scar in the healed area
Morphology of chronic ulcer:
- Classic peptic ulcer is round to oval sharply punched out defect
- During active phase shows four zones:
- Inflammatory exudate
- Fibrinoid necrosis
- Granulation tissue
- Fibrous tissue
What is the difference between acute and chronic inflammation?
Acute Inflammation:
- Inflammatory cells = neutrophils
- Vascular Damage
- More exudation
- Little or no fibrosis
- Flush, Flare, Weal
Chronic Inflammation:
- Inflammatory cells = macrophages & lymphocytes
- New blood vessels
- No/Less exudation
- Prominent fibrosis
- Little signs
