Exam 2 (Lecture 13) - Acute Inflammation Flashcards
Which cells/substances initiate acute inflammation after tissue injury or infection?
1) Histamine
2) Cytokines
3) Chemokines
4) PAF
5) Prostaglandins
6) Leukotrienes
7) Bradykinin
8) C3a/C5a
What happens after acute inflammation is initiated (activated)?
There is increased blood flow to the microvasculature
There is vadodilation
Activation of endothelium (inflammatory mediators/adhesion molecules)
What are the outcomes of acute inflammation?
1) Slowing/stasis of blood
2) Leukocyte adhesion cascade
3) Increased vascular permeability
What are the beneficial and harmful aspects of inflammation?
- Diluting and/or inactivating biologic and chemical toxins
- Killing or sequestering microbes, foreign material, necrotic tissue, and neoplastic cells
- Degrading foreign materials
- Providing wound healing factors to ulcerated surfaces and traumatized tissue
- Restricting movement of appendages and joints to allow time for healing and repair
- Increasing temperature in the body or locally to induce vasodilation and inhibiting replication of some microbial agents
**These same mechanisms can be harmful if they are over-done/not regulated!
What is the purpose of acute inflammation?
1) To kill and/or eliminate the cause of injury (microbes, foreign material, thermal, radiation, etc)
2) To phagocytose and remove debris
3) To repair the damage, thereby returning the tissue to normal structure and function
**Acute inflammation progresses chronologically in sequence through three phases: fluidic, cellular, and reparative.
What are the characteristics of acute inflammation?
- The response to injury begins as active hyperemia, characterized by an increased flow of blood to injured tissue (vasodilation)
- Redness and heat in tissues such as skin following injury (facilitated by chemical mediators)
- In vasodilation, vascular flow is slowed (i.e. vascular congestion); so there’s fluid leakage
- Leakage of plasma and plasma proteins into the interstitium mainly through inter endothelial cell gaps in the post capillary venules.
- This leakage also causes swelling and pain by stretching pain receptors in the interstitium.
Describe the fluidic (exudative) phase of the acute inflammatory response.
Purpose:
- Dilute and localize the inciting agent/substance
Increased blood flow (active hyperemia) to the site of injury
Increased permeability of capillaries and postcapillary venules to plasma proteins and leukocytes
Emigration of leukocytes (via the leukocyte adhesion cascade) into the perivascular area
Describe the cellular phase of the acute inflammatory response.
Transudate
Follows the fluid phase
Principal function:
- To deliver leukocytes into the exudate at the site of injury
- They internalize agents/substances through phagocytosis and, as required, for killing and/or degradation
What is the leukocyte adhesion cascade?
Margination followed by:
- rolling
- adhesion
- transendothelial migration
Describe the cellular phase of the acute inflammatory response with respect to neutrophils.
Neutrophils are often the first type of leukocyte recruited into the inflammatory exudate.
- Purpose of neutrophils:
- to kill microbes (bacteria, fungi, protozoa, and viruses)
- to kill tumor cells
- to eliminate foreign materials
The average transit time in the blood is 10 hours.
Neutrophils within tissue survive from 1-4 days.
Cytokines (IL-1 and TNF) and growth factors (IL-3, GM-CSF, and G-CSF) maintain neutrophil concentrations in a steady-state manner under normal physiologic conditions.
What is the function of chemical mediators in acute inflammation? Give some examples of chemical mediators.
Examples:
- Histamine
- Serotonin
- Bradykinin
- Tachykinins
Bind to receptors on target cells and often activate target cells or cause the target cell to secrete additional inflammatory mediators.
Have short half-lives and decay rapidly
Are destroyed enzymatically
Are scavenged by protective mechanisms such as antioxidants
Are blocked by endogenous inhibitors such as complement inhibitors and decoy receptors
Provides a checks and balances system on the severity of the acute inflammatory response
Distinguish between transudate and exudate.
Transudate:
- Low specific gravity (1.010)
- Low protein concentration
- Low cellularity
- Clear fluid
Exudate:
- Increased specific gravity (~1.020)
- Increased protein (>4 g/dl)
- Increased cellularity
- accumulates over time
- Cloudy, opaque fluid
What is the complement cascade?
A unique sequence of molecular events occurring within the vascular system.
Effects are:
- proinflammatory
- chemotactic
- opsonizing
- antigen solubilizing
- antibody inducing
- permeability enhancing
- microbial cell lysis
Nearly 10% of serum proteins are complement factors.
Classical, Alternative, and Lectin pathways.
Activation: Results in formation of a membrane attack complex (MAC) that perforates the cell membranes of foreign invaders and naive host cells.
Describe the arachidonic acid metabolites of acute inflammation.
When inflammation or inflammatory mediators injure cells, the cell membrane lipids are rapidly rearranged to create a variety of biologically active lipid mediators derived from arachidonic acid.
Arachidonic acid metabolites from COX isoenzymes induce an intermediate prostaglandin PGH2, which is converted into at least 5 metabolites.
What do prostaglandins contribute to in acute inflammation?
1) Fever (via PGE2)
2) Inflammatory tachycardia
3) ACTH response
4) Behavior stress syndrome (reduced movement and loss of social contact)
5) Clotting/hemostasis (vis prostaglandin and thromboxane)
