Exam 2 (Lecture 14) - Acute & Chronic Inflammation Flashcards
What are the 5 cardinal signs of inflammation?
1) Redness
2) Heat
3) Swelling
4) Pain
5) Loss of function
What are the three phases of acute inflammation?
1) Fluidic phase (exudative)
2) Cellular phase (transudative)
3) Reparative phase
What is the purpose of the fluidic phase?
Dilute and localize the inciting agent/substance.
- increased blood flow (active hyperemia) to the site of injury
- increased permeability of capillaries and post capillary venules to plasma proteins and leukocytes
- emigration of leukocytes (via the leukocyte adhesion cascade) into the perivascular area
What is the purpose of the cellular phase?
To deliver leukocytes into the exudate at the site of injury.
- They internalize agent/substances through phagocytosis and for killing and/or degradation.
**Remember: RAT (Rolling, Adhesion, Transendothelial (migration)
What is the purpose of the reparative phase?
Resolution
Resolution occurs ONLY if the following occur:
- the acute inflammatory response is completed IN THE CORRECT SEQUENCE
- macrophages and lymphatic vessels remove the exudate
- the inciting agent or substance is eliminated
- the stroma (connective tissue) of the affected tissue is intact and can provide support for regeneration of
epithelial cells (if not = fibrosis (scarring)
- ulcerated or necrotic epithelial cells are replaced by regeneration of adjacent epithelial cells on an intact
basement membrane
What is one important mediator of inflammation and what is its function?
Neutrophil
Phagocytosis:
entrapment of bacterium > formation of phagosome > degradation of bacterium > exocytosis of remains
Discuss the killing mechanisms of neutrophils and whether they are good or bad.
Neutrophils release free radicals, such as superoxide anion, hydroxyl radical, and nitrous oxide derivatives
- these are released into the extracellular space (it’s a cascade, so more and more keeps happening)
Killing mechanisms:
- injury vascular endothelial cells (BAD)
- inactivate antiproteases, such as alpha1-antitrypsin resulting in damage to ECM proteins (BAD)
- enhance cytokine and chemokine expression (MOSTLY GOOD; as long as it’s not over-exuberant)
- activate endothelial cells and increase adhesion molecule expression (MOSTLY GOOD; just not too much)
- increase the formation of chemotactic factors like LTB4 (MOSTLY GOOD; just not too much)
Discuss the body’s antioxidants agains the neutrophil free radicals.
The antioxidants are:
1) enzymatic, such as superoxide dismutase (SOD)
2) nonenzymatic endogenous substances, such as ceruloplasmin, transferrin, metallothionein, uric acid, and
melatonin
3) nonenzymatic dietary substances, such as vitamins A, C, and E
Discuss the “danger signals” that are associated with inflammatory responses.
Both endogenous and exogenous stimuli produce “danger” signals
- danger-associated molecular patterns (DAMPs) = related intracellular proteins or nucleic acids released
from necrotic cells at the site of necrosis
What are acute phase proteins?
Plasma proteins synthesized in the liver whose concentrations increase (or decrease) by 25% or more during inflammation. (IL-1 and TNF cause increase in acute phase proteins).
These proteins serve as inhibitors or mediators of the inflammatory response.
What are interferons?
Glycoprotein cytokines produced by lymphocytes and many other cell types in response to viruses and virus-infected cells, parasites, and neoplastic cells.
Inhibit viral replication within host cells
Activate NK cells and macrophages
Increase antigen presentation to T lymphocytes
Increase the resistance of host cells to viral infection
What happens if conditions do not allow for complete resolution of the acute inflammation?
1) Progression to chronic/granulomatous inflammation
2) Healing by fibrosis
3) Healing with increased cellularity
4) Abscess formation
Describe the progession to chronic/granulomatous inflammation.
Occurs when the acute inflammatory response fails.
Characterized by:
- persistence of the inciting stimulus for a long period of time (weeks to months)
- extensive tissue injury and necrosis (third-degree burn)
- a shift of the cellular elements of the inflammatory response from neutrophils to lymphocytes,
macrophages, and sometimes multinucleate giant cells (mononuclear cells)
- extensive connective tissue reorganization followed by fibrosis (fibroplasia) = chronic
Describe the abscess formation process.
Occurs when the acute inflammatory response fails to rapidly eliminate the inciting stimulus.
- enzymes and inflammatory mediators from neutrophils in the exudate liquefy the affected tissue and neutrophils to form pus
- myeloperoxidase enzyme in neutrophils contributes to neutrophil necrosis and liquefaction
- reptiles and birds lack this enzyme and are therefore unable to liquefy neutrophils into pus (their abscesses look different)
What are the types of abscesses?
They can have either a sterile or septic origin.
1) Septic abscess = most commonly originate from bacterial infection
- pyogenic bacteria such as staphylococcus and streptococcus commonly cause these types of abscesses
2) Sterile abscess = arise from incompletely degraded foreign bodies or from the failure of injected medications
to be completely absorbed
