Path: Inflamm: Acute, Chronic And Systemic

Front 1

what are the symp in acute inflamm?

Back 1

Immediate
Transient
Edema
Neutrophils
Fibrin
Necrosis

Front 2

what are the symp in chronic inflamm?

Back 2

Gradual
Prolonged
Fibrosis & vessels
Mononuclear cells
Collagen
Resolution of necrosis

Front 3

how does inflamm manifest in lungs?

Back 3

congested blood vessels (packed with erythrocytes), resulting from stasis. The cellular component of the response is manifested by large numbers of leukocytes (neutrophils) in the alveoli.

Front 4

what are the main vascular and cellular responses to inflamm?

Back 4

*Increased blood flow (vasodilation) : @ lower rate b/c blood becomes more viscous
*Increased vascular permeability (leakage)
*Migration of leukocytes (chemotaxis)

Front 5

normally, what pressure does a blood vessel wall feel?

Back 5

hydrostatic pressure = colloid osmotic pressure

Front 6

what leaks in transudate? exudate?

Back 6

transudate- fluid
exudate- fluid and protein

Front 7

why does transudate form?

Back 7

inc hydrostatic pressure >> dec colloid osmotic pressure

Front 8

under normal circumstances, what is the pressure in a vessel?

Back 8

Normal hydrostatic pressure (blue arrows) is about 32 mm Hg at the arterial end of a capillary bed and 12 mm Hg at the venous end; the mean colloid osmotic pressure of tissues is approximately 25 mm Hg (green arrows), which is equal to the mean capillary pressure

Front 9

why does exudate form?

Back 9

vascular permeability increases as a result of increased interendothelial spaces.

Front 10

what are some of the vascular changes in inflamm?

Back 10

*Transient Vasoconstriction
-Hemostasis (stops leaking of cut vessels)
*Vasodilation
-Prostaglandins and Nitric oxide
-Arteriole smooth muscle relaxes
*Increased Permeability (leakage)
-Transient, sustained or delayed

ex: suburn has delayed and sustained leaking

Front 11

what makes up the vessel of normal venule?

Back 11

2-3 endothelial cells held together by tight juncs

Front 12

what physical changes do venule undergo when there's a vasoactive mediator induced injury?

Back 12

endothelial retraction and gap formation

Front 13

how do leukocytes get out of vessels and into tissue?

Back 13

*Margination
– Leukocytes approach Endothelium
*Rolling
– Selectin
*Adhesion (pavementing)
– Integrin
*Transmigration (Diapedesis)
– Integrin
*Chemotaxis

Front 14

how does leukocyte att to venule surface?

Back 14

glycoprotein on leukocyte att to selectin on venule

Front 15

describe the mvmnt of the leukocyte:

Back 15

leukocytes first roll, then become activated and adhere to endothelium, then transmigrate across the endothelium, pierce the basement membrane, and migrate toward chemoattractants emanating from the source of injury.

Front 16

what are key molecs used in leukocyte extravasation?

Back 16

Different molecules play predominant roles in different steps of this process—selectins in rolling; chemokines (usually displayed bound to proteoglycans) in activating the neutrophils to increase avidity of integrins; integrins in firm adhesion; and CD31 (PECAM-1) in transmigration. Neutrophils express low levels of L-selectin; they bind to endothelial cells predominantly via P- and E-selectins. ICAM-1, intercellular adhesion molecule 1; TNF, tumor necrosis factor.

Front 17

how do cells respond to exposure to histamine and thrombin?

Back 17

redistribute P-selectin on surface of cell

Front 18

what inc binding avidity of integrins?

Back 18

chemokines and clustering of integrins
IL-1, interleukin-1; TNF, tumor necrosis factor.

Front 19

Weibel-Palade bodies have selectin to help leukocytes find what?

Back 19

where activated endothelial cells are

Front 20

how do leukocytes follow via chemotaxis?

Back 20

Increasing chemical gradient
Exogenous agents :
Bacterial N-formyl-methionine peptides
Endogenous products:
Complement (C3a & C5a)
Lipoxygenase products (LTB4)
Cytokines (TNF, IL-1)Chemokines (IL-8, α,β,γ)

Front 21

what does IL-8 attract?

Back 21

neutrophils

Front 22

what do beta chemokines attract?

Back 22

attract every inflammatory cell except neutrophils,

Front 23

what do delta chemokines attract?

Back 23

lymphocytes

Front 24

what are the steps of phagocytosis?

Back 24

Recognition and attachment
Engulfment
Killing and degradation

Front 25

what's used for recognition and attachment in phagocytosis?

Back 25

Opsonins: IgG-Fc, C3b, iC3b, collectins
Leukocyte receptors: FcgammaR, CR1/2

Front 26

how do leukocytes kill and degrade for phagocytosis?

Back 26

Oxidative burst: H2O2, HOCl
Enzyme digestion: degrade proteins, lipids and carbs

Front 27

what are some of the radicals that are made for phagocytosis? what enzymes used to make them?

Back 27

hypochlorite (HOCl•) and hydroxyl radical (•OH), and from nitric oxide (NO) it is peroxynitrite (OONO•)
myeloperoxidase and inducible NO synthase

Front 28

what neutrophil granules are used for phagocytosis?

Back 28

Specific (secondary):
Smaller, fuse with plasmalemma
Lysozyme
Collagenase IV

Azurophil (primary):
Fusion with phagosome
Myeloperoxidase, NADPH oxidase
Acid & neutral protease

Front 29

what are the classes of soluble factors?

Back 29

Paracrine cell products:
Nitric Oxide (NO)
Vasoactive amines (Histamine)
Arachidonic acid metabolites (COX,LOX)
Platelet Activating Factor (PAF)
Neuropeptides (SP)

Plasma protease systems :
Bradykinin, Kallekrein
Complement cascade
Clotting products and enzymes

Front 30

what's the purpose of the complement cascade?

Back 30

amplifies signal

Front 31

what does NO do? where does it come from?

Back 31

Vasodilates
From L-argenine, O2, NADPH, cofactors
Nitric Oxide Synthase
Endothelial, neuronal, inducible on macrophages
Inhibits rolling, adhesion of leukocytes
Antimicrobial free radicals released

Front 32

what are the vasoactive amines?

Back 32

histamine
serotonin: 5-HT

Front 33

where's histamine? when's it released?

Back 33

Stored in granules of mast cells and basophils
Released by allergen binding multiple IgE molecules on mast cell

Front 34

where's serotonin? when's it released?

Back 34

Stored in granules of platelets and enterochromaffin cells
Released when platelets aggregate

Front 35

what do serotonin and histamine mainly result in?

Back 35

vasodilating and inc permeability

Front 36

what turns membrane phospholipids into arachidonic acid?

Back 36

phospholipase A2

Front 37

what pathways is arachidonic acid involved in?

Back 37

LOX: lipoxygenase
COX: cyclooxygenase

Front 38

what factors and actions are involved in the cyclooxygenase pathway?

Back 38

prostaglandins vasodilate
thromboxane clot
prostacyclin unclot

Front 39

what factors and actions are involved in the LOX pathway?

Back 39

leukotrienes inc permeability
lipoxins oppose inflamm

Front 40

what does platelet activating factor do? how is it made? how do platelets respond?

Back 40

Vasodilates and increases permeability
100 to10,000 times more potent than histamine
also enhances adhesion, chemotaxis, oxidative burst
Fatty acid on middle C of PC replaced
“by product” of phospholipase A2
From endothelial cells, platelets
Synthesized at site of inflammation
Inactivated by PAF-specific acetylhydrolases

Front 41

what are the char of Neuropeptides? what do they do?

Back 41

Substance P is the prototype
Tachykinin family of peptides
Central & peripheral nervous system
Multiple effects
Vasodilate
Increase permeability
Pain
Capsaicin in hot peppers

Front 42

what does Hageman factor XII influence?

Back 42

influences Plasmin, Kallikrein and clotting

Plasmin activation leads to fibrinolysis and complement

kallikrein activation leads to bradykinin

Front 43

what are the effects of some complement parts?

Back 43

C5a, C3a: inflammation
C3b: phagocytosis
MAC: microbe lysis

Front 44

what mediators cause vasodilation?

Back 44

nitric oxide
histamine
cyclooxygenase

Front 45

what are the only mediators that doesn't cause increased permeability?

Back 45

nitric oxide
cyclooxygenase

Front 46

what mediators cause pain?

Back 46

cyclooxygenase
substance P
kinins

Front 47

what are antiproteases? where are they? what do they do?

Back 47

Found in serum
alpha1 - antitrypsin
Inhibits neutrophil elastase
Alveoli rupture/coalesce pulmonary emphysema
alpha2 – macroglobulin
In both serum and secretions

Front 48

what are antioxidants? what do they do?

Back 48

Scavenge
O2•, H2O2, HO•
NO2•, OONO-, RSNO
Extracellular
Ceruloplasmin
Transferrin
Intracellular
Superoxide dismutase
Catalase
Glutathione peroxidase

Front 49

where are monocytes? histiocytes?

Back 49

mono- in vessel
histio- out of vessel

Front 50

what are some main cytokine exs?

Back 50

Interleukins
-Monokines: L-1
-Lymphokines:IL-2
Macrophage activators:
-IFNgamma , TNFalpha , TNFbeta , IL-5, IL-10, IL-12
Hematopoietic growth factors:
c-kit ligand, GMCSF, MCSF, G-CSF, stem cell factor
Chemokine:
α C-X-C, β C-C, γ C (2 of 4 cysteines)

Front 51

what cytokines are involved in acute inflammation?

Back 51

TNF
IL-1
IL-6
chemokines

Front 52

what are the principle sources of acute inflamm cytokines?

Back 52

TNF: Macrophages, mast cells, T lymphocytes
IL-1: Macrophages, endothelial cells, some epithelial cells
IL-6:Macrophages, other cells
chemokines:Macrophages, endothelial cells, T lymphocytes, mast cells, other cell types

Front 53

what are the principle actions of cytokines in acute inflamm?

Back 53

TNF : Stimulates expression of endothelial adhesion molecules and secretion of other cytokines; systemic effects
IL-1:Similar to TNF; greater role in fever; main 1 released by macs
IL-6: Systemic effects (acute-phase response); recruits macs --> systemic effects
chemokines: Recruitment of leukocytes to sites of inflammation; migration of cells to normal tissues

Front 54

what are the cytokines involved in chronic inflamm?

Back 54

IL-12
IFN- gamma
IL-17

Front 55

what are the principle sources of chronic inflamm cytokines?

Back 55

IL-12: Dendritic cells, macrophages
IFN- gamma: T lymphocytes, NK cells
IL-17:T lymphocytes

Front 56

what are the principle actions of chronic inflamm cytokines?

Back 56

IL-12:Increased production of IFN-γ
IFN- gamma:Activation of macrophages (increased ability to kill microbes and tumor cells)
IL-17:Recruitment of neutrophils and monocytes

Front 57

who divides in tissues: macs or neutrophils?

Back 57

macs

Front 58

what does IFNgamma activate?

Back 58

macs

Front 59

what chemokines do activated T cells make to lure in macs?

Back 59

TNF, IL-17, chemokines

Front 60

what's the outcome of acute inflamm?

Back 60

*Resolution (regeneration)
-No functional or histologic change
*Progression
-Chronic inflammation
-Granuloma: accum of histiocytes
*Abscess formation
*Healing (reconstitution)
-Collagen binder or filler
-Fibrosis (replacement by scar)

Front 61

what are chronic inflamm causes?

Back 61

*Persistent infection
*Persistent injurious agent
*Interference with healing
*Autoimmunity
*May begin with minimal acute phase
-Rheumatoid arthritis
-Atherosclerosis
-Tuberculosis

Front 62

what fighting cells are present in acute inflamm? chronic?

Back 62

acute- neutrophila
chronic- macs

Front 63

what are the diseases and causes of granulomatous inflamm?

Back 63

Tuberculosis: M. tuberculosis
leprosy- M. leprae
syphillis- T. pallidum
cat scratch disease- G - bacillus
Sarcoidosis- unknown
Crohn - intestinal bac, self-antigens

Front 64

what is the tissue reaction to the granulomatous inflamm?

Back 64

Tuberculosis- Caseating granuloma (tubercle)
leprosy- Noncaseating granulomas Acid-fast bacilli in macrophages
syphillis- Gumma: plasma cell infiltrate; central cells necrotic without loss of cellular outline
cat scratch disease- Stellate granulomawith neutrophils; giant cells uncommon
Sarcoidosis- Noncaseating granulomas with abundant activated macrophages
Crohn - Noncaseating granulomas intestine wall, dense chronic inflammatory infil

Front 65

know systemic and local effects of mac activation slide

Back 65

do it now!

Front 66

what are the 5 cardinal signs of inflammation?

Back 66

heat
redness
swelling
pain
loss of function

Front 67

what are the Acute and chronic inflammation features?

Back 67

AI=PMNs & exudate CI=mononucs & spindle cells

Front 68

3 components of the inflammatory system?

Back 68

Vascular, Cellular, Humoral Factors

Front 69

Steps of leukocyte emigration, chemotaxis and function?

Back 69

Margination, rolling, adhesion, transmigration, chemotaxis, phagocytosis, oxidative burst

Front 70

9 mediator classes?

Back 70

Clot, comp, kinin, COX, LOX, PAF, NO, amines, NP

Front 71

How cytokines transition to chronic phase?

Back 71

Mitogenic, activate macrophages, chemotactic to endothelial cells and fibrocytes

Front 72

4 causes of chronic inflammation?

Back 72

Persistent infection, persistent injury, interference with healing, autoimmunity

Front 73

Cardinal signs of acute inflammation?

Back 73

inc Blood flow = rubor, calor; inc perm = tumor;
inc cells, humoral = dolor, functio laesa