Lecture 9 2/8/24 Flashcards
What is inflammation?
reaction within a living vascularized tissue to local injury
What types of injury can occur that cause inflammation?
-infectious microbes
-mechanical trauma
-heat
-cold
-radiation
-cancerous cells
What is the purpose of inflammation?
-to dilute, isolate, and eliminate cause of injury
-to repair tissue damage resulting from the injury
What are the basics of inflammation?
-requires a stimulus
-major players are in circulation/blood
-only in living tissue
-allied with healing and repair
-can be harmful
What are the benefits of inflammation?
-dilutes/inactivates biological and chemical toxins
-kills/sequesters microbes and neoplastic cells
-degrades foreign material
-provides growth factors to help with healing phase
What are the harms of inflammation?
-can destroy normal tissue
-cardinal signs of inflammation
What are the cardinal signs of inflammation?
-heat
-redness
-swelling
-pain
-loss of function
What descriptors should be included in a morphologic diagnosis?
-severity
-duration
-distribution
-modifiers
-process
-organ
Which terms can be used to describe the severity of a diagnosis?
-minimal
-mild
-moderate
-marked
-severe
Which terms can be used to describe the chronicity of a diagnosis?
-peracute: hours
-acute: hours to days
-subacute: many days
-chronic: weeks to years
-chronic-active: ongoing acute stimulus
How can a process be determined to be acute vs. chronic?
based on the type(s) of inflammatory cells and other gross changes
Which terms can be used to describe distribution of a diagnosis?
-focal
-multifocal
-locally/regionally extensive
-diffuse
-multifocal to coalescing
-segmental
-unilateral/bilateral
-cranioventral (lungs)
Which terms can be used when having to provide a modifier for an inflammatory process?
-suppurative
-necrotizing
-ulcerative
-hemorrhagic
-lymphoplasmacytic
-granulomatous
-eosinophilic
What are some examples of terms that can be used when providing a modifier for a specific location?
-bronchopneumonia
-interstitial pneumonia
-glomerulonephritis
-portal hepatitis
Which leukocytes are involved with inflammation?
-neutrophils
-monocytes/macrophages
-lymphocytes
-plasma cells
-eosinophils
-basophils
-mast cells
Which non-leukocytes are involved with inflammation?
-endothelial cells
-platelets
-fibroblasts
What are the characteristics of inflammatory mediators?
-derived from cells or plasma
-can be produced as needed or pre-formed and stored
-short-lived
What are the master cytokines?
-IL-1
-TNF
What part of the arachidonic acid pathway is inhibited by steroids?
phospholipase function
What part of the arachidonic acid pathway is inhibited by leukotriene receptor antagonists?
leukotrienes
What part of the arachidonic acid pathway is inhibited by COX-1/2 inhibitors?
cyclooxygenase
How is it possible for some membrane lipids to not form arachidonic acid (omega 6 fatty acid)?
-dietary omega 3 fatty acids insert into cell membrane
-insertion of dietary omega 3 fatty acids decreases arachidonic acid
What are the impacts of increased omega 3s in the cell membrane?
-less inflammation
-less pain
-less-free radical-mediated damage
What are the characteristics of histamine?
-pre-formed
-released in response to trauma, cytokines, etc.
What are the effects of histamine?
-vasodilation
-increased vascular permeability
-pain and itching
-eosinophil attraction
What are the steps of inflammation?
-initiation
-vasodilation
-increased vascular permeability
-activation of leukocytes
-diapedesis
-chemotaxis
-phagocytosis
What are examples of potential stimuli for inflammation?
-infectious agents
-trauma
-abnormal cells
-necrotic cells
-foreign material
Why do stimuli trigger inflammation?
PRRs on epithelial cells and leukocytes recognize PAMPs and DAMPs
How do resident macrophages initiate inflammation?
-recognize non-self or DAMPs
-release IL-1
How do lymphocytes initiate inflammation?
-recognize non-self
-release IL-1
How does direct damage to cells initiate inflammation?
-damage to mast cells leads to mast cell degranulation/histamine release
-release of IL-1
How does indirect damage initiate inflammation?
-sunburn irritates keratinocytes
-keratinocytes release IL-1
How does amplification of signaling initiate inflammation?
-IL-1 can trigger mast cell degranulation
-histamine triggers more IL-1 release
What occurs during vasodilation?
-increased blood flow to area causes heat and redness
-slowing of blood leads to margination of neutrophils
What effect does histamine, IL-1, and TNF have on the blood vessels?
makes endothelial cells contract, causing leaky vessels
How does increased vascular permeability result in edema and an increase in marginated neutrophils?
-fluid leaks out of vessels, resulting in hemoconcentration
-increased viscosity of blood leads to blood “sludging”
-sludging of blood results in more marginated neutrophils
What is lost due to increased vascular permeability?
-fluid
-proteins/fibrinogen
What happens when fibrinogen is exposed to collagen outside of the vessels?
triggers the clotting cascade, leading to fibrin formation
How do IL-1 and TNF play a role in increased vascular permeability?
increase expression of adhesion molecules, increasing the number of marginated neutrophils
Which adhesion molecules are present on vessel endothelial cells?
-E-selectin
-P-selectin
-ICAM-1
How do IL-1 and TNF increase leukocyte binding, in terms of the leukocyte?
increase the expression and avidity/stickiness of integrins on leukocyte surface
How are histamine, TNF, and IL-1 involved in leukocyte activation?
-upregulation of adhesion molecules
-increase in cytokine and prostaglandin production
What are the characteristics of diapedesis?
-movement of leukocytes out of vessels
-primarily neutrophils
-depends on upregulation of adhesion molecules
-mediated by PECAM-1
