Exam #1: Acute Inflammation I Flashcards
What is the definition of inflammation?
Inflammation is the LOCAL reaction of VASCULARIZED tissue to injury
*No vasculature & no injury= no inflammation
List the timescale for acute, subacute, & chronic inflammation?
Acute= 0-2 days Subacute= 2-14 days Chronic= >14 days i.e. greater than 2 weeks
*Less than 2 days= acute & greater than 2 weeks= chronic; the middle is subacute
What inflammatory cells mediate acute inflammation?
Neutrophils
What inflammatory cells mediate subacute inflammation?
- Neutrophils
- Monocytes
- Lymphocytes (B, T & NK Cells)
- Plasma cells
- Fibroblasic elements
- Angioblastic elements
What inflammatory cells mediate chronic inflammation?
Mononuclear cells:
- Monocytes that become macrophages once they’re out of the vascular system
- Lymphocytes
- Granuloma cells= macrophage changed cells
Describe the time course of inflammatory cell infiltration.
The hallmark of acute inflammation is increased vascular permeability leading to the escape of protein-rich exudate into the extravascular tissue, causing edema
- Neutrophils are the primary cells present on Day 1
- By ~Day 2 Monocyte/ Macrophages are more abundant
What are the characteristics of eosinophils?
- Eosinophils contain pink granules
- Present normally as 5-10 %
- Predominant inflammatory cells in allergic reactions & parasitic infestations
If you see eosinophilia i.e. an eosinophil concentration greater than 5-8%, what should you consider?
- Allergic reaction
- Parasite infections
List the plasma derived molecules that take part in the inflammatory response.
- Immune system cells (Ab, C3, C5fragments)
- Kinin system (bradykinin)
- Clotting (thrombin)
- Fibrinolytic (plasmin)
- Acute phase proteins (CRP, ceruloplasmin, haptoglobin)
List the tissue derived molecules that take part in the inflammatory response.
- Vaosactive amines (histamine & 5-HT)
- Acidic lipids (prostaglandins, leukotrienes, lipoxins)
- Cytokines (IL-1, TNF) & chemokines (IL-8)
- Others (PAF, NO, ROS, lysosomal enzymes)
Why is inflammation a “double-edged” sword?
Inflammation is fundamentally protective
- Rids the organism of initial cause of injury
- Rids the organism of consequences of injury
However, inflammation & repair may be potentially harmful
- Underlies chronic inflammatory disease
- Hypersensitivity
- Scarring
What are the six cardinal signs of inflammation? What causes these six cardinal signs?
1) Heat= increased blood flow
2) Redness= increased blood flow
3) Swelling= accumulation of water & cells
4) Pain= pressure of fluid & effect of mediators
5) Loss of function secondary to above
6) Systemic changes= release of humoral factors
List the various causes of acute inflammation?
- Infection
- Trauma
- Physical injury from thermal extremes of from ionizing radiation
- Chemical injury i.e. poisons
- Immunologic injury
- Tissue death i.e. inflammatory changes that occur in viable tissue adjacent to necrotic areas
Describe the serous pattern seen in acute inflammation.
Serous= outpouring of watery, protein-poor fluid
E.g. pleural effusion & skin blisters
Describe the fibrinous pattern seen in acute inflammation.
- Seen in more severe injury
- Increased vascular permeability leads to leakage of larger fibrinogen molecules
E.g. fibrinous pericarditis
What happens with fibrinous patterns of inflammation?
1) May resolve over time by fibrinolysis & normal tissue structure restored
2) If not resolved, will lead to ingrowth of fibroblasts & blood vessels (organization)–>scarring
Describe the suppurative pattern seen in acute inflammation.
Suppurative (purulent) inflammation= large amounts of pus (neutrophils, necrotic cells, & edema)
- Pyogenic organisms e.g. streptococci are notorious for causing this type of infection
E.g. acute appendicitis
What is an abscess? What happens when an abscess is NOT resolved?
An abscess is a focal collection of pus with central necrotic region surrounded by a “preserved” layer of neutrophils
*This may become walled off by fibroblastic proliferation
Describe the pattern of ulceration seen in acute inflammation.
Ulceration= local defect, excavation produced by sloughing of inflammatory necrotic tissue
- Acute= neutrophils & vascular dilation
- Chronic= fibroblastic proliferation
*Can only occur on or near a surface i.e. skin & mucosa
E.g. inflammatory necrosis of the mucosa of the mouth, stomach, intestines, GU tract, or subcutaneous tissue of lower extremities…“Peptic ulcers are a good example”
What are the four possible outcomes of acute inflammation?
1) Resolution
2) Healing by scarring
3) Abscess
4) Progression to chronic inflammation
What are the key events of acute inflammation?
1) Changes in vascular caliber that lead to increased blood flow
2) Structural changes that enable plasma proteins & leukocytes to leave the circulation
3) Emigration of leukocytes from microcirculation & their accumulation in the focus of the injury
What hemodynamic changes occur in the vasculature during acute inflammation?
- Initial & transient vasoconstriction followed by vasodilation–>increased flow
- Increased vascular permeability at the level of the postcapillary venules
What is transudation?
Fluid leakage seen in conditions of:
- Increased hydrostatic pressure
- Decreased colloid osmotic pressure
Transudate is a fluid with low protein content, little or no cellular material, and a low specific gravity; essentially, this is an ultrafiltrate of blood plasma
*The connection between endothelial cells are still “tight” enough that proteins are NOT leaking out
What is exudation?
Fluid AND protein leakage in conditions of (inflammation):
- Widening of endothelial junctions
- Monocytes, lymphocytes, and neutrophils leak
Thus, the difference between transudate & exudate= protein
What are the consequences of “leakage” in the vasculature?
- Edema
- Stasis of circulation resulting in increased viscosity
- Decreased absorption from interstitial space
Describe the process of leukocyte extravasation.
1) Migration
2) Adhesion
3) Emigration
4) Chemotaxis
What is the function of a fliopodium?
Movement in the direction of chemotaxis
Describe the mechanism of leukocyte exudation.
1) Rolling
2) Adhesion due to selectins & integrins
3) Transmigration in the direction of chemotaxis
What are cell adhesion molecules?
Membrane proteins that promote leukocyte attachment & participation in the inflammatory response
- Selectins (rolling)
- Ig family
- Integrins (adhesion)
What are selectins? What is their function?
- Ca++ dependent lectins expressed non-specifically
- Serve as the homing receptors that mediate ROLLING of leukocytes along the endothelium at sites of inflammation
- NOT involved in firm adhesion
- Slow down circulating leukocytes
*****Selectins= rolling
What are the different classes of selectins?
P-selectin= platelets E-selectin= endothelium L-selectin= leukocytes
What is ICAM-1?
This is the LIGAND for LFA-1 & MAC-1 INTEGRINS
- “Intercellular adhesion molecule-1”
- Assists in localization of leukocytes to tissue injury
- Expressed on ENDOTHELIUM
- Binds integrins, LFA-1 & Mac-1 present on neutrophils & macrophages
What is VCAM-1?
This is the LIGAND for VLA-4 INTEGRIN
- “Vascular cell adhesion molecule”
- Binds integrin VLA-4 on lymphocytes, monocytes, eosinophils, and basophils
What is PECAM-1?
This is an adhesion molecule present in the intercellular junction between endothelial cells that is involved in the migration of leukocytes
- “Platelet endothelial cell adhesion molecule” or CD31
*Plays and important role in the diapedesis step of leukocyte emigration
What are integrins?
- Group of adhesion molecules that are expressed on leukocytes & composed of heterodimers of alpha & beta subunits, which act in regulation of cell-matrix & cell-cell adhesion
- Transmembrane proteins that link the exterior of the cell to the cytoskeleton
What are B1 integrins?
VLA-4 is an B1 integrin expressed on leukocytes that binds VCAM-1 on endothelial cells
What are B2 integrins?
“Leukocyte function associated antigens”
- LFA-1 & Mac-1 ICAM-1 to assist in localization of phagocytes to injury sites and subsequent extravasation
