Inflammation Flashcards
acute inflammation is a response to
recent injury or infection
what is acute inflammation characterized by?
vasodilation
increased capillary permeability
neutrophils are main players
what is chronic inflammation a response to?
variable response to ongoing injury or infection
what is chronic inflammation orchestrated by?
t-helper cells
t-cells, b-cells, macrophages, eosinophils, fibroblasts may be involved
is inflammation infection? Immunity?
inflammation is not infection or immunity
what did Celsus describe?
manifestations of inflammation
-redness, heat, mass, pain
what did Virchow do?
added a fifth manifestation of inflammation
-loss of function
triple response of Lewis
red scratch
flare around scratch
swollen area around flare
1 & 3 mediated by histamine, 2 by autonomics
hallmarks of acute inflammation
vasodilation
increased capillary permeability
neutrophil infiltration
vasodilation-1
increased blood flow-redness and heat
increased capillary premeability-2
leakage of fluid and proteins
osmotic water loss-swelling
leakage of fibronigen leads to clotting
neutrophil infiltration-3
margination, emigration, chemotaxis
phagocytosis & degranulation-pain
monocytes/macrophages appear later
margination
neutrophils adhere to capillary walls
emigration (diapedesis)
neutrophils pass through capillary walls
chemotaxis
neutrophils follow chemical signals to damage/infection
phagocytosis
neutrophils engulf pathogens and debris
degranulation
neutrophils release cytoplasmic granules
what is due to histamine?
vasodilation and capillary permeability
what does margination depend on?
neutrophil and endothelial “adhesion molecules”
what drives diapedesis and chemotaxis?
C5a and various leukotrienes
what does phagocytosis rely on
opsonins IgG and C3b
what does degranulation release?
prostaglandins
leukotrienes
free radicals
lysosomal enzymes
what interferes with many aspects of neutrophil function?
steroids and diabetes
leukotrienes
act as chemotaxins
opsonins
enhance phagocytosis, make bacteria desirable to neutrophils
frustrated phagocytosis
lysosomes become extracellular when neutrophil can’t eat bacteria, spills out into cytoplasm
inflammatory mediators
chemicals responsible for aspects of inflammation
histamine
released from tissue mast cells during injury or infection
vasodilation & capillary permeability
bradykinin
formed from kinin system
vasodilation and capillary permeability
causes pain (bee venom)
complement system
collection of plasma proteins that under certain circumstances react with each other in a chain reaction-cascade
types of cascades
classical and alternate
classical and alternate cascades
two different chain reactions that ultimately lead to the same thing
C3a/C5a
stimulate mast cells to release histamine
what happens when you have an exaggerated amount of histamine?
you can go into anaphylaxis
C5a
acts as perfume, chemotaxin
C3b
opsonin, enhances phagocytosis
what is the end result of the complement system cascade-classical and alternate?
collection of complement proteins C5-C9 combine together to form membrane attack complex, punches holes in membranes
arachidonic acid metabolites
phospholipase A2 liberates AA from cell membranes
what is phospholipase A2 inhibited by?
steroids
cyclooxygenase
converts AA into prostaglandins
what inhibits cyclooxygenase?
aspirin and NSAIDs
5-lipoxygenase
converts AA into leukotrienes
what does cyclooxygenase produce?
prostaglandins
list prostaglandins
produced by cyclooxygenase
thromboxane A2
Prostacyclin (PGl2)
Prostaglandin E2
thromboxane A2
produced by platelets
vasoconstriction, platelet aggression
prostacyclin PGl2
produced by endothelial cells
vasodilation, prevents platelet aggression
prostaglandin E2
vasodilation, potentiates bradykinin(pain), fever
what does lipoxygenase produce?
leukotrienes
list leukotrienes
produced by lipoxygenase
leukotriene C4
leukotriene B4
leukotriene C4
increased capillary permeability
breaks down to LTD4 and LTE4
each causes smooth muscle constriction
leukotriene B4
neutrophil and monocyte chemotaxis
monokines
released from monocytes/macrophages
produce acute phase reaction
what are included in acute phase reaction?
interleukin-1 and tumor necrosis factor alpha (cachectin, TNF-a)
acute phase reaction
“sick” from inflammatory illness
shift in hepatic protein synthesis, more complement, clotting, c-reactive protein
-increased erythrocyte sedimentation rate (“sed rate”)
sed rate
nonspecific marker for course of inflammation
c-reactive protein
risk factor for coronary disease
what does SIRS stand for?
systemic inflammatory response syndrome
what is SIRS?
exuberant production of inflammatory mediators
what does SIRS result in?
multisystem organ failure due to normal tissue damage
who is affected by SIRS?
super sick people in ICU
what is the outcome of acute inflammation where neutrophils win?
complete resolution with no tissue damage
what is the outcome of acute inflammation where neutrophils win but there are civilian casualties?
healing by scarring
what is the outcome of acute inflammation where neutrophils cannot destroy but wall off?
abscess formation-“put” in a confined space other than a body cavity
what is the outcome of acute inflammation where neutrophils and mediators cannot remove the noxious agent?
progression to chronic inflammation
what is chronic inflammation defined as?
infiltration of mononuclear cells
-monocytes, lymphocytes, plasma cells
does chronic inflammation include immune?
some crossover into immune system activation may be present
what can chronic inflammation produce?
granulomas-macrophages adhere to each other and wall off stuff
granulomatus diseases/disorders
foreign bodies
tuberculosis
deep fungal infections
sarcoidosis
what is the predominant cell in infections by common bacteria (staph, strep, gram-negative rods)?
neutrophil
what is the predominant cell in spirochete diseases (syphilis and Lyme)?
plasma cell
what is the predominant cell in tuberculosis and fungal infections?
monocyte/macrophage
what is the predominant cell in infections caused by worms?
eosinophil
how could there be no inflammatory reaction?
depending on agent and host
example-diabetic on steroids
what are the 2 courses following inflammation for damaged tissue?
regeneration of functional cells
repair by fibrous tissue (“scar”)
labile cells
continuous replicators
ex. epithelium
stable cells
discontinuous replicators
don’t normally regenerate but have capacity
glandular cells, fibroblasts, endothelium, osteoblasts, liver regeneration
permanent cells
non-replicators
glia, neurons, heart
repair-does damaged epithelium keep free edge?
No, cannot tolerate.
rapid re-epithelization by regeneration
what replaces damaged cells?
connective tissue replaces permanent cells
how does connective tissue replace permanent cells?
fibroblasts proliferate
-produce ground substance & collagen fibers
endothelial cells proliferate
-form new, leaky vessels
both invade and eventually displace the clot
what is an immature scar?
granulation tissue
what happens in maturing scars?
enough collagen to fill the void
re-epithelization completes
type III collagen replaced by type I
fibroblasts contract & return to rest
Most new vessels resorb
Never attains strength of original tissue
what is the ideal situation for wound healing?
primary intention
what does a surgical would healing by primary intention look like?
little necrosis
no infection (hopefully)
edges approximated
primary intention: minutes
clotting cascade activated, stops the bleeding
primary intention: 24 hours
neutrophils enter, epithelial cells are regenerating from the edges
primary intention: 3 days
macrophages enter, granulation tissue appears, epithelial cells now cover the wound surface
primary intention: 5 days
granulation tissue fills the entire wound
primary intention: 2 weeks
fibroblasts multiply, collagen accumulates
primary intention: 4 weeks
overlying epidermis complete sans adnexal structures, capillary involution & scar contraction occurring, red scar turns white
what does secondary intention mean?
wound that can’t be closed or won’t be due to high risk of infection, heavily contaminated
what does secondary intention look like?
no approximation
what happens in secondary intention?
larger fibrin meshwork (scab), more inflammation, possibly infection, more granulation tissue, spectactular wound contraction
what happens after complete re-epithelization in secondary intention?
scab is pushed off
how long does it take for secondary intention to heal?
much longer than primary intention
what does secondary intention produce?
always a deformity
contracture
fibroblasts contract too much, can be crippling
what causes contracture?
burns, ugly surgery
hypertrophic scar
exuberant scar tissue formation
does hypertrophic scar go beyond wound margins?
no, stays within wound margins
does hypertrophic scar regress?
yes
keloids
exuberant scar tissue formation
do keloids go beyond wound margins?
yes, usually enlarge
hindrances to adequate healing
NOT OLD AGE inadequate nutrition-protein, vitamin C, zinc poor blood supply foreign bodies infection glucocorticoid (steroid) therapy
