Inflammation Flashcards
5 cardinal signs of inflammation
dolor (pain), tumor (swelling), rubor (erythema), calor (heat), functio laesa (loss of function)
stages of acute inflammatory response
irritation, sensation, activation of vascular/cellular responses, leukocyte migration, invasion, evacuation, systemic rejection
transudate
not due to increased vascular permeability, no increase in protein concentration, occurs with osmotic or hydrostatic imbalance (i.e. nephrotic syndromes)
exudate
acute inflammatory fluids due to increased vascular permeability, protein & cellular debris present
4 possible types of acute inflammation
serous, fibrinous, suppurative, ulcerative inflammation
pus
a purulent exudate composed of many neutrophils and necrotic cell debris with/without microbes
abscess
part of suppurative inflammatory response
ulcer
focal erosion of a superficial tissue plane (usually skin or mucosal surface) with active acute inflammation. margins become more defined with chronicity
morphology of chronic inflammation
presence of lymphocytes, macrophages, eosinophils, neutrophils. alteration of tissue architecture
morphology of granuloma
aggregates of epithelioid histocytes/activated macrophages with multinucleated giant cells. if necrotizing, caseous necrosis is present.
mechanism of granulomatous inflammation
foreign antigen activates CD4 T cell, which produces cytokines (TNF, IL17) that recruit monocytes to activate (INF gamma) tissue macrophages=fusion to giant cells and granuloma.
general causes of inflammation
microbial infections, necrotic tissue, physical agents, foreign bodies, immune rxns, trauma, chemical agents
ultimate goal of inflammatory process
phagocytosis and restoration of tissue integrity and function
characteristics of acute inflammation
rapid onset, short duration, increased tissue fluid, accumulation of neutrophils
characteristics of chronic inflammation
longer duration, infiltration of macrophages/monocytes/lymphocytes, alteration of tissue histoarchitecture including fibrosis
pathophysiology of rubor/calor
vascular dilation, increased blood flow during acute inflammatory response
pathophysiology of tumor
increased vascular permeability leading to tissue edema and accumulation of neutrophils
pathophysiology of dolor
chemical mediators such as bradykinin
pathophysiology of function laesa
tissue damage, pain, swelling
components of acute inflammation
vascular and cellular response
three major processes of acute inflammation
- alterations in vascular caliber that lead to an increase in blood flow
- structural changes in the microvasculature that permit plasma proteins and leukocytes to leave circulation
- emigration, accumulation, activation of leukocytes to eliminate offending agent
components of acute inflammatory vascular rxn
vasodilation (histamine, NO), increased permeability (endothelial gaps due to histamine, bradykinin, leukotrienes), stasis, leukocyte accumulation
components of acute inflammatory cellular rxn
leukocyte extravasation (cell surface molecules), leukocyte activation (arachidonic acid metabolites/cytokines), phagocytosis, termination of inflammatory response
increased permeability via gaps due to endothelial contraction
histamine, bradykinin, leukotrienes
mechanisms for increased vascular permeability
endothelial gaps, direct injury, leukocyte mediated injury, increased transcytosis pathways, new vessel formation (inherently leaky)
edema
increased fluid in interstitial tissues or serous cavities
effusions
pathologic accumulation of fluid in a body cavity
ascites
specific term for an effusion of the abdominal or peritoneal cavities
adhesion molecules in acute inflammation
selectins, immunoglobulin family adhesion proteins, integrins
selectins
(E,P,L-selectins) expressed on leukocytes and endothelial cells that facilitate the rolling of neutrophils. but don’t bind to each other
Ig family adhesion proteins
(ICAM, PECAM) expressed on endothelial cells and bind to integrins on the surface of leukocytes to facilitate leukocyte adhesion and transmigration
integrins
expressed on leukocytes and participate in rolling and extravasation
chemotactic factors for neutrophils
bacterial products, complement components especially C5, arachidonic acid metabolites (leukotrienes), and kallikrein
histamine
early mediator of vascular rxn including vasodilation and increased permeability. preformed in mast cells, act mainly on endothelial receptors
serotonin
vasodilation, increased permeability. preformed in platelets (released upon aggregation) and neuroendocrine cells.
arachidonic acid
fatty acid residing in cell membrane phospholipids. can be converted into prostaglandins, leukotrienes, lipoxins, TxA2, chemotactic molecules, etc.
cytokines involved in inflammation
TNF alpha & IL1 (from inflammasome) =both local and systemic effects. fever, fatigue, endothelial effects, fibroblast effects, increased cytokine production
nitric oxide
produced by endothelial cells and macrophages, relaxes vascular smooth muscle resulting in dilation. inhibits platelet aggregation
platelet activating factor (PAF)
triggers release of histamine, activates platelets, enhance neutrophil adhesion
importance of factor 12 in inflammation
links kinin (kallikrein=chemotaxis), coagulation (intrinsic pathway), and complement systems.
leukocytosis
elevated white blood count (left shift, bandemia)
erythrocyte sedimentation rate (ESR)
nonspecific test for systemic inflammatory response. increased fibrinogen leads to rouleaux formation and increased density=faster sedimentation
how does increased fibrinogen cause rouleaux formation?
it reduces the surface negative charge on cells so that RBCs don’t repel each other and actually clump together
when is ESR increased?
inflammation, malignancy, pregnancy
when is ESR decreased?
polycythemia, sickle cell anemia, congestive heart failure, hypofibrinogemia, microcytosis
serous inflammation
fluid collection (vascular>cellular). blisters
fibrinous inflammation
vascular permeability increases sufficiently to allow increasingly large molecules such as fibrinogen to lead to sticky coagulum (common on body linings)
suppurative inflammation
inflammatory exudate composed of bacteria, sloughed/necrotic cells, and neutrophils
4 possible outcomes of acute inflammation
complete resolution, abscess formation, chronic inflammation, scar formation
complete resolution of acute inflammation
most often occurs when injurious agent is eliminated and process is short lived.
abscess
cavitated lesion of acute inflammation with central accumulation of neutrophils plus cell and tissue debris. over time a fibrous ring separates the cavity from the surrounding tissue
chronic infection initiator cells
macrophages via INF-gamma
causes of granulomatous inflammation
TB!!!!, mycobacteria, leprosy, syphilis, foreign bodies, autoimmune mediated, etc
