Week 3: Inflammation Flashcards
Allostatic Load
Is an index of the cumulative wear and tear on the body caused by repeated activation of multiple physiologic systems over time in response to environmental demands in an effort to maintain internal equilibrium
Identify the cytokines involved in the vascular and cellular responses of the inflammatory process including vasodilation, vascular permeability, pain, systemic manifestations of inflammation, repair and healing and phagocytosis
Cytokine are a family of intercellular-signaling molecules that bind to specific cell receptors and regulate innate or adaptive immunity. They can be pro-inflammatory or anti-inflammatory, synergistic or antagonistic, pleiotropic (same molecule can have many different biologic activities), and include interleukins, interferons, and tumor necrosis factor (TNF)
Vascular Response
Vascular Response: after initiation by the plasma protein system, mast cells, tissue macrophages, and dendritic cells, the inflammatory response has an almost immediate effect on the blood vessels.
1. Hemostasis (coagulation): injury to blood vessels initiates the clotting cascade and activates platelets
2. Vasodilation: arteriole and venule dilation increase the diameter of blood vessels, increasing the volume of blood to the injured area - contributes to redness and warmth in the area
3. Increased vascular permeability: blood vessels become more porous resulting in exudation and edema of the area
4. Leukocyte cell adhesion: leukocytes adhere to the inner walls of vessels
Together, these vascular changes deliver leukocytes (particularly neutrophils and macrophages), plasma proteins, and other biochemical mediators to the site of injury
Explain the role of the three plasma protein systems of inflammation
Protein systems that provide a biochemical barrier against invading pathogens, activated early in inflammation.
1. Complement system
2. Clotting system
3. Kinin system
The activation of the first component of a system results in sequential activation of other components, this is called a cascade.
State the five cardinal signs of acute inflammation and describe the physiologic mechanisms involved
- Redness (vasodilation - increased blood flow)
- Heat (vasodilation - increased blood flow)
- Swelling (increased capillary permeability)
- Pain (stimulation of nerve endings)
- Loss of function
Differentiate between acute and chronic inflammation
Chronic inflammation is inflammation that lasts 2 weeks or longer and is often related to an unsuccessful acute inflammatory response. Characteristics include:
- dense infiltration of lymphocytes and macrophages
- granuloma formation
- epithelioid cell formation
- giant cell formation
Explain the pathophysiology that results in local and system manifestations of inflammations
Local manifestations: result from vascular changes and corresponding leakage of circulating components into the tissue - functions to dilute toxins, carry plasma proteins and leukocytes to the injury site, carry bacterial toxins and debris away from the site, initiates healing
Explain the role of gut microbiome and dysfunction in the pathogenesis of inflammation
The microbiome interacts with the body in a beneficial way to foster healthy defense systems:
- induces protective immune responses & supports immune tolerance of innocuous micro-organisms
- synthesizes metabolites
- releases antibacterial substances
- competes with pathogens for nutrients
- blocks attachment of the pathogens to the epithelium
- produces enzymes that aid digestion of fatty acids & polysaccharides
Some members of the normal bacterial microbiome are opportunistic pathogens - that is, they are harmless under normal conditions but can cause disease in immunocompromised individuals who lack the usual defense mechanisms.
Discuss the common laboratory tests used to help diagnose inflammation
An increase in the total number of WBCs in combination with an abnormal differential count suggests there may be an ongoing infection and/or inflammatory response.
Hepatic synthesis of many plasma proteins is increased during inflammation
- measurement of acute-phase reactants
- fibrinogen
- ESR “sed rate”
- C-reactive protein (CRP levels from 1 mg/dL to 10 mg/dL are thought to be a moderate increase. CRP Levels greater than 10 mg/dL are considered a marked increase.)
The normal number of WBCs in the blood is 4,500 to 11,000 WBCs per microlite
Describe Innate Barriers
Form the first line of defense at the body’s surfaces. These barriers can be physical, mechanical, and biochemical.
Define Inflammation
A response that is meant to both protect against injury and illness and also support healing.
- Occurs in tissues with blood supply (vascularized)
- Rapidly initiated
- Involves activities of cellular and chemical and vascular components
- Non-specific - takes place in approximately the same way regardless of the type of stimulus or past occurences
- No memory cells
Cellular Response
- Neutrophils
- Macrophages
- Phagocytosis
Complement System
Intensifies, activates or collaborates with other components of the inflammatory response - “complements” them. When activated, initiates proteolytic steps (breakdown of proteins into smaller substances) these can destroy pathogens directly or enhance the activity of other components to kill pathogens.
Anaphylatoxin activity resulting in mast cell degranulation, leukocyte chemotaxis, opsonization, cell lysis
Activation of the complement system can be accomplished in three different pathways, all of which activate the protein C3:
1. Classical pathway
2. Lectin pathway
3. Alternate pathway
Classical Pathway
Part of the Complement system and is activated by antibodies (adaptive immune system) bound to their specific targets (antigen). Antibodies of the acquired immune response can use the complement system to kill bacteria and activate inflammation
Lectin Pathway
Part of the Complement system; activated by mannose-containing bacterial carbohydrates
