inflammation

Question 1

what is inflammation

Answer 1

a reaction to living tissue around it, not dead tissue

Question 2

why must tissue be living an vascularised for inflammation

Answer 2

ingredients for inflammation are in circulation

Question 3

what is fibrinogen

Answer 3

clot protein
very useful in body, interstitial space
turns into fibrin

Question 4

what does inflammation deliver

Answer 4

concentrated, activated defensive materials in fluid
- phagocytes
- plasma proteins (opsonins, complement)

Question 5

what is exudate

Answer 5

delivered cells, proteins, fluid

Question 6

5 cardinal signs of inflammation

Answer 6

swelling - universal sign
warmer
painful
redness
loss of function
signs differ depending on setting but are driven by active changes in microvasculature which delivers the exudate

Question 7

how does inflammation start

Answer 7

small vessels and ECM respond to danger signals
- damaged matrix
- stressed/dying tissue cells
- mast cells
- pathogens

Question 8

second stage of inflammation

Answer 8

blood fills capillary and venular bed - redness, warmth
exudate fluid leaves capillaries/venules
interstitial matrix actively hydrates - local swelling
venous outflow becomes sluggish - stasis, congestion

Question 9

how do cytokines sustain inflammation in substantive injuries

Answer 9

perivascular mast cells degranulate and release cytokines through projections into vessels
incoming leukocytes take over

Question 10

local swelling

Answer 10

water uptake into connective tissue matrix (hyaluronan)
relaxed compression - collagen detachment and unfolding, fibroblasts relax

Question 11

hyaluronan in matrix

Answer 11

very hyrophilic
tends to be slightly hydrated as is compressed by surrounding cells so doesnt hold as much water as possible

Question 12

vascular leak

Answer 12

junction breaks between endothelial cells
capillary filtration pressure

Question 13

passive leak

Answer 13

from microvessels
usually less important

Question 14

what happens to leucocytes and platelets entering venules

Answer 14

pushed towards the walls by haemodynamics of normal blood flow

Question 15

what blocks inflammatory cells from sticking firmly to endothelium

Answer 15

thick glycocalyx ‘blanket’

Question 16

what causes endothelium to shed glycocalyx

Answer 16

DAMP and cytokines (TNF, IL-1)

Question 17

what is exposed once glycocalyx is shed

Answer 17

surface adhesion molecules like selectins
they enhance neutrophil and platelet rolling

Question 18

what do platelets boost

Answer 18

endothelial activation

Question 19

what recruits more platelets

Answer 19

fibrin stands forming on endothelium

Question 20

what happens when crawling neutrophils encounter platelets bound to endothelium

Answer 20

they move to endothelial junction to exit using proteases

Question 21

transmigration

Answer 21

pericytes guide out transmigrating neutrophils
extravasated neutrophils emerge and screen the perivascular tissue
rigidity of inflamed tissue further activates traversing neutrophils

Question 22

what seals the transmigration site

Answer 22

platelets

Question 23

what is chemotaxis

Answer 23

directed migration up a concentration gradient
phagocytes need a matrix to crawl over

Question 24

things that attract neutrophils - self

Answer 24

coagulation products
complement C5a, C3a
IL-8

Question 25

things that attract neutrophils - non-self

Answer 25

bacterial endotoxin f-met-leu-phe peptides

Question 26

what can minor damage be cloaked by

Answer 26

resident macrophages results in damage being concealed from scanning neutrophils

Question 27

what does inflammation develop in response to

Answer 27

DAMP and/or PAMP pattern recognition receptors recruit and activate immune cells, and prime adaptive immune responses

Question 28

what do changes in small blood vessels deliver

Answer 28

an exudate that contains active defenses

Question 29

what is in pus

Answer 29

neutrophil and enzyme rich

Question 30

fibrinous exudate

Answer 30

fibrin >> cells greyish sticky fibrin coating

Question 31

serous exudate

Answer 31

fluid >> cells serum like, lacking fibrinogen and platelets found in burn blisters, allergic polyps

Question 32

haemorrhagic exudates

Answer 32

vascular destruction

Question 33

lymphatics in inflammation

Answer 33

draining lymph carries immune cells, inflammatory cytokines, extracellular vesicles, matrix fragments etc. from injury site to local lymph nodes - adaptive immune responses

Question 34

what is nociception through

Answer 34

Aẟ and C nociceptor neurones

Question 35

what can influence pain thresholds

Answer 35

macrophages

Question 36

is all inflammation painful

Answer 36

no - indirect pain from adjacent structures

Question 37

systemic effects of inflammation

Answer 37

cytokine effects distant to injury IL-1β, TNF, IL-6, chemokines

Question 38

systemic effects of inflammation - liver

Answer 38

acute phase proteins fibrinogen, c-reactive proteins, serum amyloid A (IL6, IL1)

Question 39

systemic effects of inflammation - bone marrow

Answer 39

accelerated wbc release from marrow (esp neutrophilia)

Question 40

systemic effects of inflammation - CNS

Answer 40

fever sickness behaviours cytokine induced depression (chronic inflammation or immunotherapy) cognitive impairment (brain fog, chronic inflammation)