10.09 Acute Inflammation Flashcards
components of acute inflammation
- from blood
- from connective tissue
- from blood: polymophonuclear leukocytes (neutrophils), lymphocytes, platelets, monocyte, clotting factors, eosinophil and basophil
- from connective tissue: mast cell, fibroblast, macrophage
five cardinal signs of acute inflammation
swelling, redness, temperature, pain and loss of function
granulocytes
- neutrophils (PMNs)
- eosinohpils (more for hypersensitivty)
- basophils
- macrophages (mostly for chronic inflammation but also in the late stages of acute inflammation).
vascular event
- vasoconstriction
- vasodilation
- exudation
- stasis
- adhesion and rolling
- margination (pavementing)
vascular event: vasoconstriction
temporary and neurological response.
when body senses pressure or injury, it initially constricts blood vessels to minimize bleeding. it’s followed by vessel dilation
vascular event: vasodilation
starts from artery to capillaries to vein.
increased hydrostatic pressure pushes fluid out of vessels into the injured site.
vascular event: exudation
fluid leakage
- endothelial cells contract to produce interendothelial gaps
- increased vascular permeability
- immediate transient (hrs), immediate prolonged (physical damage to vessels; days), and delayed prolonged (e.g., sunburn)
- mild (watery, serous; bullous disease-bollous dermititis)
- moderate (fibrinous: some proteins; “bread and butter” pericarditis)
- supprative (purulent, puss, pyogenic; acute appendititis)
- severe (hemorrhage)
vascular event: stasis
- blood thickens and slows down (due to decrease in fluid from exudation)
- RBCs stick together in the middle of the vessel and WBCs are pushed out
vascular event: adhesion and rolling
- in normal state, WBCs and endothelium have same elec. charges. During inflamm., endoth change elec. charges.
- activated macrophages in the site releases cytokines that leak thru endoth to attrack WBCs to endoth.
- leukocytes temporarily bind to endoth at P- and E-selectin >> integrin on leukocyte bind to integrin ligand (ICAM-1) for more stable adhesion >> PECAM-1 (CD31) on both leukocyte and endoth bind to allow leukocyte to squeeze through endothelium into the tissue
- chemotaxis: chemicals released from the injured site create chemotactic factor gradient which attrack neutrophils
vascular event: margination (pavementing)
lining of the blood vessels with WBCs
cellular events
- emigration (diapedesis)
- chemotaxis
- opsonization
- phatocytosis
cellular events: emigration (diapedesis)
- pavementing and migration
- squeezing through the endothelium into the tissue
cellular event: chemotaxis
- drawing of cells through chemotactic gradient secreted by activated macrophages
cellular event: opsonization
- opsonins: molecular taggs attached to offending agents for neutrophil recognition
- complement 3 breakdown product
- non-immune immunoglobulin G (IgG)
- plasma carbohydrate-binding lectins (collectins)
- receptors: C3b, Fc and C1q
cellular event: phagocytosis
- attachment of neutrophil to opsonized agnet >> engulfment >> discharge of lysosomal granule contents into phagosome >> killing and digestion of agent (using ROS and RNS)
- lysosomes don’t wait until phagosome is completely formed: lysosomal substances can leak out and destroy nearby anything >> can lead to significant damage
plasma-derived mediators for acute inflammation
- clotting-fibrinolytic: factor XIII, plasmin
- kinins: e.g., bradykinin
- complement: e.g., C3a,b, C5a,b proteins
- C3b attaches to microbe for recognition
- C3a and C5a recruits and activates leukocytes
- factor XII starts the cascade
- kinin cascade will inhibit the whole process
- clotting cascade will continue the process leading to acute inflamm.
cell-derived mediators for acute inflammation
- arachidonic acid derivatives (leads to production of prostaglandins, etc)
- PG, TX: cyclooxygenases
- LT, LX: lipoxygenases
- vasoactive amines from mast cell: histamine and serotonin
- cytokines: IL-1/TNF
- nitric oxide from macrophages: stimulates vascular smooth muscle relaxation and vasodilation (also results in leukocytes and platelet adhesion).
arachidonic acid
- when worked by 5-lipoxygenase: leads to vasoconstriction and increased permeability
- when worked by 12-lipoxygenase: leads to vasodilation, inhibition of neutrophil chemotaxis and stimulates monocyte adhesion
- when worked by cyclooxygenase then prostacyclin PGI2 (from WBC), vasodilation, inhibits platelet aggregation
- when worked by COX then thromboxane A2 (from platlet), vasoconstriction and platelet aggregation.
- if just COX, leads to vasodilation and edema.
TNF/IL-1
local and systemic effects
- locally: leukocyte adhesion, activation and fibroblast prolifeation and collagen synthesis
- systemically: fever, leukocytosis, decrese appetite and more sleep
subtypes of acute inflammation: within skin
- abscesses: focal area of suppuration (puss)
- phlegmons (cellulitis): spreading of abscesses (e.g., streptococcal: tissues dissolved by neutrophils)
subtypes of acute inflammation: on surfaces: (skin, mucous membrane)
- ulcers: focal necrosis and inflammation (“crater-like”)
- pseudomembranes: diffused ulceration.
- e.g., pseudomembranous colitis: most common hospital-induced lethal disease
systemic effects of acute inflammation
- fever: endogenous pyrogens: IL-1, IL-6, TNF-alpha, PGE, NO
- leukocytosis: IL1, TNF, CSF, GSF
- acute phase reactants (produced in liver): CRP, complement, serum amyloid A (SAA)
acute inflammation outcomes
- resolution
- abscesses: mass tissue destruction that needs phagocytosis
- chronic inflammation: if acute wasn’t enough
