1-Inflammation

Question 1

inflammation

definition

Answer 1

reaction of tissue and its microvasculature to some type of insult (infection or injury) = inflammation mediators syn and movement of fluid and leukocytes into tissue from blood

Question 2

4 cardinal signs

Answer 2

1. redness aka rubor
2. swelling aka tumor
3. heat aka calor
4. pain aka dolor

Question 3

inflammation

purpose

Answer 3

1. remove pathogenic insults
2. remove injured tissue
3. institute wound healing

so without inflamm infections go unchecked and wound healing not proceed

Question 4

types of inflammation

Answer 4

1. acute= fluid + neutrophils, hours or days
2. chronic = lymphocytes + macrophages, offending agent not removed, weeks/months/years

Question 5

potential outcomes

Answer 5

1. resolution- removing offending agents and restore normal tissue architecture
2. abscess- offending agent walled off by inflamm cells and destruction of the walled off tissue by released products of neutrophils
   -still get partial resolution
   -cut open
3. scarring- tissue irreversibly injured even though offender is gone
4. chronic inflamm- if acute fails to remove offender

Question 6

acute inflamm pathway

first steps

Answer 6

1. injury
   -immediate vasoconstriction
   -exposed collagen/basement membrane
   -mast cell activation

then more advanced steps, other cards

Question 7

exposed collagen/BM pathway

Answer 7

1. exposed collagen/BM
2. hageman factor activation
3. production of anaphylatoxins + bradykinin

bradykinin (chem mediator of pain) = pain and edema

Question 8

hageman factor activation

pathway

Answer 8

1. converts pre-kallikrein to kallikrein
   -kallikrein cleaves C5 into C5a/b + converts high M Wt. Kininogen to bradykinin
2. converts plasminogen to plasmin
   -plasmin cleaves C3 into C3a/b

C3a and C5a are anaphylatoxins

Question 9

mast cell activation pathway

Answer 9

1. mast cell activated/degranulated by direct trauma, injury, cold, heat, anaphylatoxins
2. release histamine + syn prostaglandin 2
3. vasodilation from histamine
4. heat + redness (vasodilation) pain (PGE2)

Question 10

vascular permeability

histamine effect

Answer 10

histamine > inc vascular permeability = escape of protein rich fluid ‘exudate’ thru gaps in b/t endothelial cells

exudate inc osmotic pressure of interstitial fluid + inc hydrostatic prssure from vasodilation = edema

inc permeability sustained by LTC/D/E4 from mast cells

histamine gives 3/4 cardinal signs

Question 11

neutrophil extravasation

Answer 11

1. stasis of circulation = margination of PMNs along endothelium bc can detect changes
2. rolling- P selectin from weibel palade bodies of endothelium bind P selectin glycolipid 1 (PSGL1)from PMN loosely
3. binding- ICAM1 on endothelial surface binds LFA1 on PMN to stop rolling bc high affinity
4. extravasation- PECAM1 @ intracellular junctions pulls PMN thru endo cells then penetrate BM with metalloproteinases
5. chemotaxis to site of inflamm by chemokines binding proteoglycans to leave gradient

E selectin hours later but P first
both xpress PECAM

Question 12

initiation of wound healing

Answer 12

macrophages secrete transforming growth factor beta (TGFB) to induce migration of fibroblasts to site and secrete collagen

monocytes (baby macros) and macrophages high 24-48 hrs after start of inflamm

Question 13

predispose conditions

chronic inflamm

Answer 13

1. persistent infections from bacteria or fungal pathogens
2. chronic exposure to toxic agents- silicosis
3. autoimmune disease- rheumatoid arthritis and lupus

Question 14

hallmarks of chronic inflamm

Answer 14

1. infiltration of macrophages and lymphocytes
2. tissue destruction mediated by enzymes released by macros (elastase, collagenase, phosphatase, lipase)
3. attempts at healing (angiogenesis, fibrosis)

Question 15

systemic effects

when?

Answer 15

1. pathogen gains entrance into bloodstream, sepsis
2. severe local injury that inflamm mediators released into bloodstream

ex. fever, neutrophilia, acute phase response, shock

Question 16

chemokines

Answer 16

TNF
IL-1
IL-6

if too high levels then pathologic, otherwise protective

Question 17

NLRP3 inflammasome

Answer 17

combination of NLRP3 + adaptor + caspase-1 to produce IL-1 for acute inflamm

Question 18

fever pathway

Answer 18

1. infections/toxins
2. IL-1 + TNF + IL-6
3. hypothalamus
4. PGE2 as cytokine messanger
5. vasomotor center
6. sympathetic nerves
7. skin vasocontriction
8. dec heat dissipation
9. fever

Question 19

fever advantages

Answer 19

1. dec viral/bacterial replication/growth
2. inc antigen processing and specific immune response bc functions more effectively at higher temps
3. protect host cells from deleterious effects of TNF

cyclooxygenase inhibitors like aspirin block PGE2 syn so reduce fever

Question 20

neutrophilia

Answer 20

inc peripheral blood neutrophils
-commonly accompanies acute inflamm

IL-1/6/TNF = accelerate release of PMNs from bone marrow then sustained by macrophages
-T lymphocyte dervied release of granulocyte colony stimulating factor

Question 21

acute phase response

Answer 21

in systemic inflamm from macrophage derived IL-6 on hepatocytes to syn/release acute phase proteins
-c reative protein that opsonizes like IgG and CB3

inc plasma levels of protein = accelerate erythrocyte sedimentation rate

Question 22

shock

Answer 22

from deleterious effects of TNF in blood stream
-systemic vasodilation + vascular permeability = intravascular volume loss > hypotension and shock
-systemic activation of coagulation system aka DIC = multiorgan failure and serious bleeding
-death