Lecture 6: Systemic Features of Inflammation, Chronic Inflammation Flashcards
What regulates temperature/fever?
Preoptic area of hypothalamus (autonomic nervous system)
What does a higher temperature do in fever?
Enhance metabolism of neutrophils / inflammatory cell function, kill bacteria (?), increase phagocytosis (?)
What is nonpyrogenic hyperthermia?
Regulatory set point unchanged; physiologic mechanisms can’t dissipate heat
What causes nonpyrogenic hyperthermia?
Heat stroke (temperatures), increased head production, exercise/seizure/metabolic disorders, malfunctioning regulatory center (CNS lesion)
What is pyrogenic hyperthermia?
Change in thermoregulatory set-point in hypothalamus
Macrophages stimulated to release IL-1, TNF, IL-6 (endogenous pyrogens) –> local production of PG in hypothalamus
What are examples of pyrogens?
Toxins from bacteria, inflammation, immune response, cancer, some pharmacologic agents, viruses
What is thought to be a life-threatening fever?
Above 105.8 F
Adverse effects of fever:
Inactivity, anorexia, discomfort, seizures
What does acetaminophen do?
Block COX-3
- Reduce fever centrally in hypothalamus
- Inhibit central pain signals in brain
Works faster than ibuprofen for fever
What does ibuprofen do?
- Decrease inflammation, and therefore pain
What causes lymphadenitis?
Inflammatory mediators, debris, infectious organisms draining into nodes
What is lymphangitis?
Inflammation of lymphatic channels; characterized by red streaks
What are acute phase proteins?
Proteins that appear in plasma early in inflammation; not normally present, or present in low amounts.
IL-1, TNF, and IL-6 increase production of these in the LIVER.
List some examples of acute phase proteins.
Fibrinogen, serum amyloid A, C-reactive protein, C3, haptoglobin
What is C-reactive protein?
Bind to cell surfaces to increase binding of complement proteins/bacteria
- activate alternative pathway
- indicate chronic inflammation
What inhibits inflammatory reaction?
alpha1-antitrypsin
What is serum amyloid A (SAA)?
Acute phase protein, may be involved in secondary amyloidosis (chronic diseases)
What is increased erythrocyte sedimentation rate?
Red cells fall more quickly with settling of blood in inflammation
- presence of increased fibrinogen
Indicator of chronic inflammatory disease (like lupus)
What is leukocytosis?
Increases in leukocytes (primarily neutrophils) in infection (primarily bacterial, sometimes infarction)
What are reasons for leukocytosis?
- Marginated cells are stimulated by IL-1, TNF, IL-6 (and IL-8)
- Increase in synthesis (CSF)
- Early release from marrow (immature - bands)
Lymphocytosis is seen in _______
viral infections
Leukocytosis is a _____ fold increase usually seen in _____ hours
2-3; 72
What is the numerical mark for leukocytosis?
Total white count > 10,000
Neutrophils > 80% (8000)
Increase in bands (
What does an increase in eosinophils look like and mean?
Allergies/parasites
> 5% of differential count or >500 per microliter
What increases eosinophils?
IL-5 (Th1 response with increased IgE due to IL-4)
What hypersensitivity is associated with eosinophils?
Type I
Collect at sites due to chemokines from mast cells along with histamine
What are examples of pathology that is systemic inflammation?
Septic shock, SIRS (systemic inflammatory response syndrome), vascular leak syndrome, DIC, anaphylaxis
How is inflammation resolved?
- Apoptosis of neutrophils
- Anti-inflammatory mediators
- Removal of debris
What are some anti-inflammatory mediators?
Lipoxins, resolvins, protectins, acute phase reactants
3 outcomes for inflammation:
- complete resolution
- healing and regeneration
- chronic inflammation
What continues inflammation in the chronic state?
Macrophages - continue to stimulate immune response, especially with persistent antigen
What causes fibrosis?
Fibroblasts from chronic macrophage activation; collagen formation and cross-linking
Scar tissue
