PoD - Acute Inflammation Flashcards
1
Q
what is inflammation?
A
- series of dynamic, protective changes occurring in living tissue in response to injury
2
Q
what are the cardinal signs of inflammation?
A
- rubor (redness)
- calor (heat)
- tumor (swelling)
- dolor (pain)
loss of function
3
Q
what are the causes of AI?
A
- micro-organisms
- trauma to the tissue
- chemical (upset stable environment)
- physical (extreme environmental environment)
- dead tissue (necrosis irritates adjacent tissue)
- hypersensitivity
4
Q
where does AI happen?
A
- series of microscopic events
- localised to affected tissue
- takes place in the microcirculation (extracellular space)
- results in clinical symptoms
5
Q
what are the main steps in AI?
A
- changes in vessel radius = flow
- changes in the permeability of the vessel wall
- emigration of neutrophils
6
Q
what happens to change the vessel radius?
A
- transient arteriolar constriction
- local arteriolar dilation
- relaxation of vessel smooth muscle
7
Q
how does increasing radius of vessel impact flow?
A
- a small change in radius makes a vast change in amount of flow
- increased arteriolar radius causes increased local tissue blood flow
- causes redness and heat
8
Q
what happens as a result of changes in cell wall permeability?
A
- net movement of plasma from capillaries to extravascular space
- called exudation
- oedema is accumulation of the exudation - swelling of tissue in acute inflammation
- swelling causes pain (stretching of nerves) - aims to reduce function (protective)
9
Q
how does increased permeability change blood flow?
A
- loss of fluid = increased viscosity (thicker)
- reduced rate of flow (stasis)
- causes RBCs to aggregate in centre and neutrophils to move towards edge
10
Q
what is the most important cell in AI?
A
- neutrophil polymorphonuclear leukocyte
11
Q
what are the phases of neutrophil emigration?
A
- margination (neutrophils move to endothelial aspect of lumen)
- pavementing (neutrophil adhere to endothelium)
- emigration (neutrophils squeeze between endothelial cells to extravascular tissues)
12
Q
what is the ideal outcome of AI?
A
- offensive agent isolated and destroyed
- macrophages move in from blood and phagocytose debris, then leave
- epithelial surfaces regenerate
- inflammatory exudate filters away
- vascular changes return to normal
- inflammation resolves
13
Q
what are the benefits of AI?
A
- rapid response to non-specific insult
- transient protection of inflamed area
- neutrophils destroy organisms and denature antigen for macrophages
- plasma proteins localise process
- resolution and return to normal
14
Q
what are neutrophils?
A
- mobile phagocytes
- recognise foreign antigen
- move towards it
- adhere to organism
- release granular contents (oxidants/enzymes)
- phagocytose & destroy foreign antigen
15
Q
what are the consequences of neutrophil action?
A
- neutrophils die when granule contents released
- produce pus
- may extend into other tissues, progressing the inflammation
16
Q
what plasma proteins are present in inflammation?
A
- fibrinogen - coagulation factor, forms fibrin which is involved with clotting - localises the inflammatory process
- immunoglobulins - specific for antigens
17
Q
what are the effects of mediators?
A
- vasodilation
- increased permeability
- neutrophil adhesion
- chemotaxis
- itch and pain
18
Q
what do releasing histamine do?
A
- histamine is stored as preformed granules in mast cells
- released as a result of local injury (IgE mediated reactions)
- causes vasodilation, increased permeability
- acts via H1 receptors on endothelial cells
19
Q
what is serotonin’s role in inflammation?
A
- preformed in platelets
- released when platelets degranulate in coagulation
- involved in vasoconstriction
20
Q
what are prostaglandins?
A
- produced in many cells (endothelium cells, leukocytes)
- mostly promote histamine action and inhibit inflammatory cells
- has be known to promote platelet aggregation and vasoconstriction
21
Q
what are cytokines/chemokines?
A
- molecules produces by macrophages, lymphocytes, endothelium in response to inflammatory stimuli
- different molecules have different effects (pro-/anti-inflammatory)
- stimulate intracellular pathways
22
Q
what is PAMP?
A
- pattern associated molecular patterns
- pattern on microbial antigen that immune cells are hard wired to recognise
23
Q
what is DAMP?
A
- danger associated molecular patterns
- substances released in response to stimulus
- stimulate pattern recognition receptors on cell membrane
- activate inflammatory response
24
Q
what is MAPK?
A
- mitogen-activated protein kinase
- stimulated in inflammation via surface receptors (TLRs)
- regulate pro-inflammatory cytokine production and inflammatory cell recruitment
25
what is JAK-STAT?
- janus kinase signal transducer and activator to transcription
- direct translation of extracellular signal to molecular expression
26
how is plasma involved in coagulation?
- coagulating factors present in plasma
| - fibrinogen concerted to fibrin to form clots
27
what happens in fibrinolysis?
- process of breaking down fibrin, helps to maintain blood supply
28
what does kinin system do?
- produces bradykinin which is associated with pain
29
what are the immediate effects of inflammation ?
- pyrexia (raised temperature)
- feel unwell (malaise, anorexia, nausea)
- neutrophilia (raised WBC count)
30
what are the longer term effects of inflammation?
- lymphadenopathy (lymph node enlargement)
- weight loss
- anaemia
31
what is suppuration?
- pus formation
32
what is pus?
- collection of dead tissue, organisms, exudate, neutrophils, fibrin, RBCs, debris
- (pyogenic) membrane surrounds pus to localise it
33
what is an abscess?
- collection of pus under pressure
- can be single or multi-loculated
- tends to point and produce discharge
- can collapse which indicates healing and repair
34
what is the outcome of organisation?
- granulation tissue present
- tends to have a patch-job look
- formed of new capillaries (angiogenesis), fibroblasts & collagen (lay down new tissue) and macrophages (clear debris)
- leads to fibrosis and formation of scar
35
what are the effects of systemic infection?
- shock (inability to perfuse tissues)
| - septic shock - vasodilation/tachycardia/hypotension/pyrexia
36
how does septic shock occur?
- systemic release of chemical mediators from cells into plasma leads to vasodilation (loss of systemic vascular resistance - causes heart rate to increase to match cardiac output)
- bacterial endotoxin released (pyrexia)
- activation of coagulation (haemorrhagic skin rash)
- HR insufficient to maintain CO = low BP
- reduced perfusion of tissues (tissue hypoxia --> loss of cell tissue/organ function)
37
what is the outcome of septic shock?
- rapidly fatal
- tissue hypoxia
- haemorrhage
- requires urgent intervention and support
38
what are the microscopic characteristics of CHRONIC inflammation?
- inflammation in which the cell population is especially:
lymphocytes
plasma cells
macrophages
- features of tissue/organ damage - healed with patch
- signs of healing and repair (granulation tissue/scarring/fibrosis)
39
what are the clinical presentations of CI?
- non-specific 'sore' bit
- malaise and weight-loss
- loss of function
40
when do we get CI?
- typically follows on from acute inflammation (large volume of damage, inability to remove debris, failure to resolve)
- can arise as a primary lesion
41
what is angiogenesis?
- the formation of new blood vessels
- vascular endothelial growth factor (VEGF) is released by hypoxic cells which stimulates proliferation
- enzyme secretion aids process
- enables blood supply to enter damaged tissue
42
what is the link between angiogenesis and tumour growth?
- angiogenesis occurs as the tumour grows
| - more angiogenesis = increased growth
43
what is primary chronic inflammation?
- where there is no initial phase of acute inflammation
- autoimmune diseases are an example of 1st CI where auto-antibodies are directed against own cell and tissue components. Destroy or damage organs, tissues, cells (lupus)
44
what is the role of a lymphocyte in CI?
- T cells (helper/killer) and B cells
- B cells = differentiate into plasma cells (antibodies) which facilitate immune response, act with macrophages and make up immune memory
- T cells = produce cytokines (attract/hold/activate immune cells), produce interferons (anti-viral effects, attract other cells), damage & kill antigen (chemical granule proteins)
- NK cell = destroy antigens and cells
45
what is the role of a macrophage in CI?
- remove debris
- presents antigens
- mobile phagocyte is able to move from blood, contain enzyme (lysozome) and other chemicals which destroy cells and influence inflammation
46
what is the role of fibroblasts in CI?
- motile cells
- metabolically active
- make and assemble structural proteins (collagens)
47
what is granulomatous inflammation?
- granulomas (granulomata) in tissues and organs
| - stimulated by indigestible antigen - body can't get rid of it
48
what is a granuloma composed of?
- macrophages
- giant cells
- neutrophils
- eosinophils
- dead material
Often surrounded by lymphocytes
49
what are giant cells?
- fusion of macrophages to form larger cells
- large cytoplasm w/ multiple nuclei
- Langerhans type and foreign body type (associated with pyogenic granulation tissue, acutely inflamed, pus)
50
what are examples of infectious granulomatous diseases?
- tuberculosis (mycobacterium tuberculosis)
- leprosy (mycobacterium leprae)
- syphilis (treponema pallidum)
51
what are examples of non-infectious granulomas?
- rheumatoid disease (tissue specific auto-immunity)
- sarcoidosis
- Crohn's disease
52
how does surgical wound and larger wound healing, differ?
```
Surgery
- healing by primary intention
- minimal gap - blood clot
- small amount of granulation tissue
- small linear scar
Larger Wounds
- healing by secondary intention
- lots of granulation tissue ingrowth
- puckering/contraction of skin and scarring (messy)
```
53
what is the sequence of events in wound healing?
- injury, blood clot, acute inflammation, fibrin
- many growth factors & cytokines involved
- granulation tissue growth - angiogenesis
- phagocytosis of fibrin
- myofibroblasts move in and lay down collagen
- contraction of scar
- re-epithelialisation
54
what helps wound healing?
- cleanliness
- clean edges
- sound nutrition
- metabolic stability and normality
- normal inflammatory & coag mechanisms
- local mediators
55
what is a callus after bone fracture?
- after a bone fracture, osteoblasts lay down new bone
- nodules of cartilage present
- bone remodelling (osteoclasts remove dead bone, progressive replacement of woven bone by lamellar bone, reformation of cortical/trabecular bone)
