inflammation Flashcards
(26 cards)
inflammation
response of vascularised tissue to offending agents by bringing cells and molecules from circulation to eliminate the offending agent
causes of inflammation
- infection and toxin -> biological agents
- tissue necrosis (body treats dead cells as foreign bodies)
- foreign bodies
- immune reactions (autoimmunity) -> misdirected inflammation
physical agents (heat, cold, radiation)
cells and molecules involved in inflammation
leukocytes (WBC)
- neutrophil, lymphocyte, macrophage
mediators in inflammation
- histamine (vasodilation)
- prostaglandin (vasodilation, pain, fever)
- cytokine (TNF, IL-1, IL-6) -> systemic effects like fever, leukocyte recruitment and activation)
- chemokine (induce chemotaxis -> direct the migration of WBC)
- bradykinin (pain)
impt of vessels
vascularised tissue provide passageway for immune cells and molecules to travel to injury site
acute vs chronic inflammation
onset
A: fast
C: slow (days)
cellular infiltrate
A; neutrophils
C: monocytes/macrophages and lymphocytes
tissue injury
A: mild and self-limited
C: severe and progressive
local and systemic signs
A: prominent
C: less
amt of inflammatory exudate
A: exudation faster
C: exudation slower or absent
cardinal signs of inflammation (local)
redness (vasodilation)
swelling (exudate)
pain (stimulation of nociceptive nerve fibres)
warmth (vasodilation)
loss of function (damaged tissue)
mast cell degranulation
release of inflammatory mediators by mast cells via exocytosis
3 groups of inflammatory mediators
- histamine (preformed in granules)
- eicosanoids (thromboxane, leukotriene, prostaglandin) -> simple non protein molecules synthesised in cytoplasm
- cytokine (continuous) -> protein
pathogenesis of inflammation
- Mast cells secrete histamine and prostaglandins. Macrophage secrete prostaglandins.
- histamine and prostaglandin cause vasodilation -> redness and warmth
- vasodilation cause large gaps between endothelial cells of inner lumen of blood vessels so exudate leaks out -> swelling
- Kinin in exudate activated to bradykinin which irritate the nociceptive fibers, prostaglandins sensitise fibers to bradykinins to transmit pain
- pain and swelling contribute to loss of function
- blood flow in vasodilated blood vessel is slower, allowing neutrophils to undergo margination
- selectins on endothelial cells slow neutrophils down (margination) and integrins on neutrophils force them to stop, undergoing adhesion to the endothelium (pavementing)
- chemokines released by inflammatory cells (mast cells, macrophages) allow neutrophils migrate out of blood vessel
- neutrophils attracted to site of action by leukotrienes, bacterial product and complements phagocytose offending agents or release toxic contents
- macrophages secrete cytokines (TNF-alpha, IL-1) which augment inflammatory process
- more selectin and integrins (improved adhesion of neutrophils)
- increased killing ability of neutrophils
- stimulate systemic response (promote prostaglandin production to cause fever since high temo bad for bacteria)
neutrophil emigration
- margination of neutrophil (slow down and roll along)
- pavementing of neutrophil (adhere to wall of of blood vessel)
- pass between capillary endothelial cells which contract, widening fenestrations (gaps)
- extravasation of neutrophil lead to inflammatory exudate
exudate vs transudate
exudate -> due to inflammation
transudate -> due to haemodynamic disorder
5 systemic symptoms of inflammation
fever (TNF, IL-1) -> prostaglandin raise body temp by increasing heat production and decreasing heat loss (thermoregulation)
- heat augments performace of immune cells, place stress on pathogen and infected cells
reactive hyperplasia of lymphoreticular system (swelling of lymph nodes)
amyloidosis -> misfolded proteins (amlyoids) deposited around body
- bone marrow producing more immune cells -> more mistakes (make amyloids)
anorexia, malaise, nausea
haematological changes
- anemia -> bone marrow produce more inflammatory cells like neutrophils so insufficient RBC made
- leukocytosis -> elevated WBC
outcomes of acute inflammation
actue inflammation
- vascular changes
- neutrophil recruitment
- mediators
- acute ->resolution
- clearance of stimuli
- clearance of mediators and acute inflammatory cells
- replacement of injured cell -> regenerative capacity
- normal function -> minimal death and damage - acute -> fibrosis
- loss of function - acute -> pus formation (abscess) -> fibrosis
- acute -> chronic -> fibrosis
- acute progress to chronic with
- angiogenesis
- mononuclear cell infiltrate (migration of lymphocyte and monocytes through endothelium of post capillary venule -> drain blood from capillary)
- fibrosis (scar)
must ensure to treat acute inflammation so it doesn’t progress to more serious manifestations like 2,3,4
factors that determine if inflammation goes to resolution
- type of tissue involved
eg brain tissue cannot be regenerated and undergo liquefactive necrosis - period of injury
longer, more likely for fibrosis - amt of tissue destruction
- nature of agent
eg bacteria cause more damage if it forms abscess
special patterns of acute inflammation
- serous -> when exudate has low immune cells and doesn’t involve infection (eg blister)
- fibrinous -> when
there is increased fibrinogen in exudate, causing fibrin threads to form . usually in sacs (pleura, pericardium) (eg pericarditis) - suppurative ->
when there is pus. if localised, it is an abscess - ulcer -> when there is defect on epithelial surface (eg gastric ulcer)
systemic inflammation
- can result in sepsis
- offending agent at original site was not well controlled, causing it to spread
pros and cons of inflammation
pro
- dilution of toxic
- entry of antibodies
- fibrin formation
- delivery of oxygen and nutrients
- stimulation of immune response
con
- digestion of normal tissue
- swelling
-inappropriate inflammatory response
chronic inflammation
response of prolonged duration where inflammation, tissue injury and attempts at repair coexist
- can follow acute inflammation or without (eg autoimmune disease, endogenous material or exogenous material
causes of chronic inflammation
- persistent infection -> resist elimination
- hypersensitivity disease (eg autoimmune disease, allergies)
- prolonged exposure to toxic agent
(eg endogenous -> atherosclerosis from cholesterol or exogenous -> suture)
role of macrophages in chronic inflammation
macrophage has 2 types depending on the cytokines activating it
M1: destruction
M2: synthesis
function:
- clearance: M1 macrophage clear inflammatory site of cell debris
- building: M2 macrophages secrete cytokines and growth factors for ECM synthesis
what are CD4 T cells in the context of chronic inflammation
immune cells that influence actions of macrophages via cytokines
diseases involving chronic inflammation
- alzheimer disease
- heart disease
- type 2 diabetes
- rheumatoid arthritis
- cancer
perforation
cancer: constant injury so cells continously repair themselves through mitosis, mutations and damages accumulate and the cells turn cancerous)
Chronic inflammation is a combination of 3 simultaneous processes. They are?
inflammation
- involves macrophages (not neutrophils), lymphocytes
attempts at repair
- fibrosis and angiogenesis
tissue injury
- by persistent offending agent and inflammatory cells
granulomatous inflammation
type of chronic inflammation often associated with TB
key features
always: granuloma- aggregates of epitheliod histiocytes
often: Langhans Giant Cells (clumped macrophages with horseshow shaped ring of nuclei), T cells, Caseous necrosis
causes of granulomatous inflammation
- specific infections that are difficult for the body to get rid of (eg fungi, TB, parasites, syphilis)
- materials resistant to digestion (endogenous- keratin exogenous- silica, suture materials)
- chemicals and drugs
