Inflammation and repair

Question 1

describe the classic vascular changes and cellular events of the inflammatory rxn

Answer 1

vasodilation
increased vascular permeability
accumulation and activation of leukocytes at site of injury

Question 2

what are the alterations in endothelial barrier during acute inflammation

Answer 2

-endothelial contraction (post cap venules )
-endothelial cell retraction ( structural rearrangement of cytoskeleton)
- direct endothelial injury ( necrosis due to bacterial enzymes)
-delayed prolonged response (mech unknown)
-

Question 3

Mediators of increased vascular permeability : Endothelium derived

Answer 3

nitrous oxide -relaxing factor

• platelet-activating factor
• prostaglandins

Question 4

Mediators of increased vascular permeability: mast cell/ basophil degranulation

Answer 4

histamine

Question 5

Mediators of increased vascular permeability: platelets

Answer 5

serotonin

Question 6

Mediators of increased vascular permeability: inflammatory cells

Answer 6

• platelet activating factor , PG and leukotrienes

Question 7

Rubor and Calor

Answer 7

Redness and warmth :

• due to vasodilation of arterioles which increases blood flow
• key mediator is histamine which causes a relaxation of arteriolar smooth muscle

Question 8

Tumor

Answer 8

swelling :

due to leakage of fluid from postcapillary venules into the interstitial space (exudate)

Question 9

dolor

Answer 9

pain

bradykinin and PgE2, sensitize sensory nerve ending

Question 10

Fever

Answer 10

pyrogens (LPS from bacteria) cause macrophages to release IL-1 and tNF which increase cyclooxygenase activity in perivascular cells of the hypothalamus
- increase in PGE2 raises temperature set point

Question 11

describe the steps involved with isolation and destruction of an infectious agent by neutrophils

Answer 11

1. margination -( vasodilation slows blood flow and cells start to flow from center to periphery)
2. rolling -( selectin “speed bumps” are upregulated on endothelial cells, sialyl Lewis X on Leukocytes bind to the selectin)
3. Adhesion -( ICAM and VCAM are upregulated on endothelial (TNF and IL-1) . integrins are upregulated on leukocytes (C5a and LTB4) . interact and firm adhesion
4. transmigration and chemotaxis -( migrate across postcapul venules toward chemotaxis ( IL-8, C5a, LTB4)
5. phagocytosis -( enhanced by opsonins IgG and C3b)
6. destruction of phagocytosed material - ( O2 dependent killing is the most effective HOCl from oxidative burst kills microbes . O2 independent killing - enzymes present in leukocyte secondary granules
7. resolution
   - neutrophils undergo apoptosis and disappear within 24 hrs after resolution of the inflammatory stimulus

Question 12

mediators of acute inflammation

Answer 12

Toll like receptors ( TLRs) 
Arachidonic acid metabolites 
mast cells 
complement 
Hageman factor (XII)
neutrophils

Question 13

mediators of acute inflammation : TLRS

Answer 13

• present on cells of the innate immune system ( macro, dendritic)
• activated by PAMPs
• CD-14 -> LPS on gram -
• TLR activation -> upregulation of NK-kappa beta

Question 14

mediators of acute inflammation - arachidonic acid metabolites

Answer 14

AA released from phospholipid cell membrane by phospholipase A2 and acted upon by COX or 5-lipoxygenase
-> COX -> PG
PGI1,PGD2, PGE2 mediate vasodilation and increased vascular perm.

5-lipoxygenase produces leukotrienes
-> LTB4 attracts and activates neutrophils
LTC4, LTD4, LTE4 mediate vasoconstriction, bronchospasm, increase vascular permeability

Question 15

mediators of acute inflammation : mast cells

Answer 15

activated by tissue trauma, complement C3a, C5a or crosslinking of cell surface IgE antigen
immediate response: histamine -> vasodil arterioles, increased vascular perm
delayed response: produced of arachidonic acid metabolites .

Question 16

mediators of acute inflammation : hageman factors

Answer 16

when activated activates coagulation and fibrinolytic systems, complement, kinin system

Question 17

Transudate vs exudate

Answer 17

exudate is due to increase capillary permeability ( cloudy a bunch of cells)
transudate is due to increased hydrostatic pressure (clear no cells)

Question 18

Chronic inflammation

Answer 18

lymphocytes and plasma cells in tissue

- delayed by more specific

Question 19

granulomatous inflammation

Answer 19

• granuloma - collection of epithelioid histiocytes usually surrounded by giant cells ( langerhans or foreign body) and a rim of lymphocytes

Question 20

repair

Answer 20

replacement of dead or damaged cells with vital tissue

Question 21

Labile cells

Answer 21

multiply throughout life , epithelial surface cells, lymphoid and hematopoietic cells
small and large bowel ( stem cells in mucosal crypts )

Question 22

stable cells

Answer 22

latent capacity to regenerate parenchymal cells of all glands, mesenchymal cells, endothelial ells and smooth muscle cells , liver

Question 23

permanent cells

Answer 23

DO NOT DIVIDE after development proliferation has stopped - neurons, myocardial cells

Question 24

granulation tissue

Answer 24

macrophages secrete angiogenesis factors which stimulate the growth of solid capillary buds which later form a lumen - edematous tissue rich in nutrients

• chemotactic and growth factors stimulate the ingrowth and activation of fibroblasts
• with time inflammatory cells decrease and collagen is laid down, capillaries become less prominent

Question 25

regeneration

Answer 25

-replacement of damaged tissue with native tissue; dependent on regenerative capacity of tissue -

Question 26

repair

Answer 26

replacement of damaged tissue with fibrous scar - occurs when regenerative stem cells are lost or when a tissue lacks regenerative capacity - granulation tissue is the initial phase of repair - fibroblast ( Type III collagen), capillaries ( provide nutrients) , and myofibroblasts ( contract wound) - results in scar formation -> Type III-> I

Question 27

mechanism of tissue regeneration

Answer 27

paracrine signalling via growth factors ( macrophages secrete growth factors that target fibroblasts) - interaction of growth factors with receptors results in gene expression and cellular growth - TGF-alpha -> epithelial and fibroblast growth factor - TGF-beta -> important fibroblast growth factor; also inhibits inflammation - platelet derived growth factor - GF for endothelium, smooth muscle and fibroblasts - fibroblast growth factor- important for angiogenesis and skeletal development - vascular endothelial growth factor (VEGF)- angiogenesis

Question 28

Basement Membrane VI

Answer 28

ubiquitous in microfibrils

Question 29

Basement Membrane VII

Answer 29

anchoring fibrils at dermal-epidermal junctions

Question 30

basement membrane IX

Answer 30

cartilage , intervertebral disks

Question 31

basement membrane XVII

Answer 31

transmembrane collagen in epidermal cells

Question 32

basement membrane V and XVIII

Answer 32

endostatin-forming collagens , endothelial cells

Question 33

time course for wound strength

Answer 33

- 7 days post wounding: 5-10% tensile strength of unwounded skin- low collagen content - 60-70 days post wounding: 100% collagen but only 30% tensile strength ( type III prominent) - 100 days post-wounding: 100% collagen content and 80% if tensile strength increase type I but will never return to organized strength

Question 34

healing by primary union - time course

Answer 34

Day 1- blood clot, acute inflammation Day 2- re-epithelialization of fibrin clot; fibroblast activation Day 3 - neutrophils replaced by macrophages which debride wound Day 7- wound covered with normal thickness epidermis; collagenization in granulation tissue second week- fibroblasts; vessels and collagenization-> wound is red , most inflammatory cells are gone after second week: increase in collagenization and tensile strength but less strength and elasticity than normal skin

Question 35

Defects in leukocyte adhesion

Answer 35

LAD 1 : beta 2 chain of CD11 & CD18 intergins LAD 2: ligand for E-selectin (sialyl lewix X) both result in reccurent bacterial infections and impaired wound healing

Question 36

Defects in chemotaxis

Answer 36

chediak-higashi( rare, autosomal recessive) disordered microtubule assembly -> impaired locomotion, neutropenia, and defective degranulation -diabetes mellitus complement deficiency (C5a) -chronic renal failure

Question 37

defects in leukocyte function

Answer 37

bone marrow suppression leading to leukopenia

Question 38

defects in phagocytosis

Answer 38

diabetes mellitus | - deficiency in opsonins -> immunoglobulins or complement ( C3b)

Question 39

defects in microbicidal activity

Answer 39

chronic granulomatous disease : nadph oxidase deficiency- cant make superoxide or H202 - x-linked, autosomal recessive chediak- higashi -> defective granulation myeloperoxidase deficiency -> mild other routes of killing severe G6PD deficiency blocks synthesis of NADPH