Inflammation and wound healing (year 2) Flashcards
what is inflammation?
response to injury as part of the immune response causing swelling and a leukocyte response
what injuries may causes inflammation?
infectious agents, mechanical trauma, heat, radiation, cancer, necrotic cells
what are the classic signs of inflammation?
heat redness swelling pain loss of function
why does the inflammatory response occur?
it is a protective response to try and eliminate the initial cause and consequences of cell injury
what accumulates in the extravascular system during inflammation?
leukocytes (white blood cells) and fluid
is inflammation always good?
no it can be harmful
the fluid involved in inflammation is plasma which includes proteins, name some of these proteins
clotting factors, fibrinogen, bradykinin, complement components
name the leukocytes that may be present during inflammation
neutrophils eosinophils basophils monocytes lymphocytes
what are the polymorphonuclear leukocytes?
neutrophils, eosinophils and basophils
what colour do neutrophils stain in H&E?
neither blue or pink (neutral)
what colour do eosinophils stain in H&E?
pink
what shape are the nuclei of mononuclear cells?
round
name the mononuclear cells
lymphocytes
monocyte (in circulation) and macrophage (in tissue)
what are the 4 important components/cells of inflammation?
plasma, circulating cells, endothelial cells, cells and extracellular matrix
what are the cells in the extracellular matrix?
mast cells, fibroblasts, resident macrophages and lymphocytes
what are the components of the extracellular matrix?
structural fibres - collagen
adhesive glycoproteins
proteoglycans
what are the functions of the extracellular matrix?
sequestration of water
reservoir for growth factors
substratum for cells to adhere to, grow and proliferate within
define acute inflammation with its main characteristics
short durations characterised by oedema and neutrophils
define chronic inflammation and its main characteristics
longer duration characterised by macrophages, lymphocytes, fibrosis, proliferation of blood vessels and necrosis
define exudation
escape of fluid, proteins and blood cells from the vascular system into interstitial tissues or body cavities
define transudation
escape of just fluid from the vascular system into the interstitial tissues or body cavity
how do transudates and exudates appear?
transudate - clear or lightly coloured
exudate - turbid to opaque with variable colour
what is oedema?
excess of fluid in interstitial tissue or in serous cavities
what is pus?
inflammatory exudate rich in leukocytes (neutrophils) and cell debris
acute inflammation is dominated by vascular changes, what are these?
alterations in vascular flow (increased blood flow)
structural changes in the microvasculature (leakage of plasma and proteins)
emigration of leukocytes from microcirculation
what specific vascular changes occur during acute inflammation?
vasodilation
stasis - slowing of flow
why does stasis occur during acute inflammation?
loss of fluid and increased blood viscosity
what are the three causes of increased vascular permeability?
endothelium-mediated vascular leakage
protein leakage from venules
increased hydrostatic pressure in capillary beds
what causes endothelium mediated vascular leakage?
chemical mediators such as histamines causing endothelial contraction
cytokines and hypoxia causing endothelial retraction
severe burns of lytic bacterial infections causing necrosis
activation of adherent leukocytes releasing toxic oxygen species and enzymes
what happens to leukocytes in normal laminar blood flow?
circulating leukocytes can roll on endothelial cells but won’t attach
what happens to leukocytes during stasis and vasodilation?
come into contact with the endothelial cells more so more chance to attach and send signals
what are the 5 stages of extravasation?
rolling activation adherence transmigration migration
what is the rolling stage of extravasation?
leukocytes role along the endothelium
what is the activation stage of extravasation?
leukocytes are activated
what is the adherence stage of extravasation?
leukocytes stably adhere to endothelium
what is the transmigration stage of extravasation?
leukocytes moves through the vessel wall
what is the migration stage of extravasation?
leukocytes migrate in interstitial fluid towards chemotactic stimuli
what are the two components that facilitate the interaction between white blood cells and endothelial cells?
selectins and integrins
what does the type of emigrating leukocyte depend on?
age of inflammatory lesion and type of injury/stimuli
usually in the first 6-24 hours what leukocyte is predominantly filtered?
neutrophils
usually in the 24-48 hour period after the stimuli of inflammation what leukocyte is predominantly filtered?
macrophages
what is the change of leukocyte secretion during inflammation due to?
changes to adhesion molecules and chemokine patterns
short life of neutrophils
define chemotaxis
movement of cells directed by a chemical gradient, move towards area of greatest concentration
what are chemokines?
small proteins produced by almost all cells
what are the effects of chemokines?
chemotaxis, angiogenesis, collagen production
when leukocytes arrive at their destination what is their role?
phagocytosis
what are the three steps of phagocytosis?
recognition and attachment
engulfment
killing/degredation
what happens during engulfment during phagocytosis?
foreign body is enclosed within a phagosome their is then fusion of the lysosome forming a phagolysosome and finally degranulation of lysosomal granules
what are some things that may go wrong during killing/degradation that could cause further tissue injury?
regurgitation during feeding
frustrated phagocytosis
exocytosis of granules
what are chemical mediators of inflammation?
substances that initiate and regulate the inflammatory response
where can chemical mediators of inflammation derive from?
plasma or cells
what are the features of chemical mediators of inflammation?
usually bind specifically to receptors
have direct enzymatic activity or mediate oxidative damage
name some chemical mediators of inflammation
histamine, serotonin, prostaglandins, cytokines, kinins, complement
where is arachidonic acid found?
cell membrane phospholipids
what is the function of arachidonic acid metabolites?
short lived hormones that mediate all the steps of inflammation
what are the systemic effects of acute inflammation?
pyrexia lethargy increased BP shivering redirecting blood
what causes the systemic effects of acute inflammation?
acute phase proteins
what are the four possibilities for the outcome of inflammation?
complete resolution
progression to chronic inflammation
healing by fibrosis
abscess formation
what is the best outcome of acute inflammation?
complete resolution meaning return to normal function
what must occur for complete resolution of acute inflammation?
return to normal vascular permeability drainage of fluid/proteins drainage of macrophages phagocytosis of degenerate neutrophils phagocytosis of necrotic debris by macrophages disposal of macrophages
under what specific circumstances may chronic inflammation develop from acute?
persistant infection - parasites and mycobacterium
prolonged irritation - foreign bodies and toxins
cellular immune response - autoimmunity or viral infection
several process occur during chronic inflammation, what are these?
active inflammation
tissue destruction
regeneration or repair
what cells dominate during active inflammation?
mononuclear - macrophages, leukocyte, plasma cells
what happens during regeneration/repair during chronic inflammation?
connective tissue replaces damaged tissue
angiogenesis
fibrosis
what are the cells of chronic inflammation?
macrophages
what roles do macrophages have during chronic inflammation?
phagocytosis antigen presentation (MHC II) secretes proinflammatories, procoagulants, enzymes wound healing regulates ,monocytes and granulocytes
are neutrophils and macrophages undergo cell division?
neutrophils - no
macrophages - mitotically active
other than macrophages, what cells are seen during chronic inflammation?
lymphocytes, plasma cells, mast cells/eosinophils (parasitic infection)
what is a plasma cell?
a B lymphocyte that has been triggered by an antigen to produce antibody
tissue destruction occurs in chronic inflammation induced by leukocytes, what ways does this cause damage?
lysosomal enzymes
oxygen-derived active metabolites
products of arachidonic acid metabolism
when does regeneration and repair occur in chronic inflammation?
regeneration - mild superficial injury
repair - severe injury repaired to a scar
what is the aim of regeneration/repair?
restore anatomical and functional integrity
what is the key deciding factor for whether you get regeneration or repair?
regeneration - leaves tissue framework intact
repair - damage to tissue framework
what factor plays a role in deciding if regeneration or repair occurs?
the type of tissue
what is a good example of a tissue that is good at regenerating?
skin - rapidly dividing active tissue
what are continuously dividing cells known as?
labile cells such as epidermis
what is regeneration induced by?
growth factors that initiate signalling pathways influencing the cell cycle
what is fibrosis?
deposition of collagen fibres as an attempt to replace lost tissue by fibrosis
when will fibrosis occur?
when there has been tissue damage to both parenchymal cells and stromal framework
what is fibrosis also known as?
scaring
what is the beginning stage of fibrosis?
formation of granulation tissue
how long after injury does granulation tissue begin to form?
24 hours - initial fibrin framework
what does granulation tissue contain?
new blood vessels and proliferating fibroblasts
describe the process of angiogenesis
degradation of basement membrane
migration of endothelial cells
proliferation of endothelial cells
recruitment of periendothelial cells
eventually tissue remodelling occurs, what is the granulation tissue replaced by and what does this involve?
scar
involves alteration to the composition of the extracellular matrix
what is an abscess?
suppurative (neutrophil dominated) inflammation buried in a tissue or confined space, created by necrosis
what can cause necrosis of tissue?
reduced perfusion or bacterial toxins
what is the most common cause of abscesses?
bacteria
why are abscesses difficult to treat with antibiotics?
poor blood supply
what does wound healing involve?
acute inflammation regeneration extracellular matrix synthesis remodelling of connective tissue collagenisation
what stimulates wound healing?
acute inflammation mediators growth factors cell-ECM interaction angiogenesis fibrosis
what is healing by first intention?
wounds with opposed edges (surgical wound)
what is healing by second intention?
when there is a deficit in the skin
give examples of healing by second intention
infarction, abscess, ulceration
what factors effect wound healing?
systemic - nutritional and hormonal
local - foreign material, poor perfusion, size and type of wound, infection, movement
what are some abnormalities of wound healing?
wound dehiscence
ulceration
excessive formation of repair components (exuberant granulation tissue
contraction
what is wound dehiscence?
the edges of the wound don’t meet
what are the 5 parts of a morphological diagnosis of inflammation?
degree duration distribution type of inflammation organ-itis
what are the ways of classifying the degree of inflammation?
mild, moderate, severe
what are the three ways of describing the duration of the lesion?
acute, subacute, chronic
what are the four ways of describing the distribution of the lesion?
focal, multifocal, disseminated, diffuse
how is a lesion with the duration of a few hours to days described?
acute
how is a lesion with the duration of a few to many days described?
subacute
what does a focal lesion mean?
just one area affected
what does a diffuse lesion mean?
whole organ is affected
what does a multifocal lesion mean?
multiple small lesions
what does a locally extensive lesion mean?
one large area is affected
what is a disseminate lesion?
whole organ affected but only by small lesions
what words can be used to describe the type of inflammation?
this describes the exudate
serous, fibrinous, suppurative, haemorrhage, necrotising, necrohaemorrhagic
what is a serous exudate?
think of serum
outpouring of thin fluid (transudate)
seen in blisters and other serous/mucosal surfaces
what is a fibrinous exudate?
serum and proteins, this leads to a clotted exudate found on serosal and mucosal surfaces
what is a suppurative/purulent exudate?
dominated by neutrophils
is a pus formed from necrotic tissue, neutrophils and fibrin
what is the prefix used for accumulation of pus?
pyo-
what is a pustule?
pus within the dermis/epidermis
what is an empyema?
pus within a pre-existing space
what is an abscess?
pus within a cavity which has developed due to tissue necrosis
what is a haemorrhage exudate?
dominated by blood due to severe damage of blood vessels
what is a necrotising inflammation?
exudation and severe tissue necrosis, often associated with ulcers
what is chronic active inflammation?
low level inflammation that has acute flair ups
what cells dominate granulomatous inflammation?
macrophages
what is an ulcer?
focal full-thickness defect in the epithelium surface or an organ/tissue
