Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pathology > Lec2-3 Acute and Chronic Inflammation > Flashcards

Lec2-3 Acute and Chronic Inflammation Flashcards

1
Q

Inflammation basics

A
  • ubiquitous, fast, non-specific rxn of vascularized tissue to local injury
  • functions:
  • – defend and stop aggression
  • – clean up [phagocytosis]
  • – repair
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Characteristics of acute inflammation

A
  • interstitial edema

- accumulation neutrophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

3 major steps of acute inflammation

A
  • alteration vascular caliber to increase blood flow
  • structural change in microvasculature so plasma proteins and neutrophils can leave circulation
  • emigration of neutrophils from microcirculation and accumulation in injury site
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

5 Classic signs of inflammation

A

Present in acute inflammation

  • heat [calor]
  • redness [rubor]
  • edema [tumor
  • pain [dolor]
  • loss of function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Characteristics of chronic inflammation

A
  • presence of mononuclear cells
  • – lymphocytes, plasma cells, macrophages
  • admixed with granulation tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Cause of acute inflammation

A
  • microbial infection
  • physical agents
  • chemicals
  • necrotic tissue
  • immunologic reactions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

4 Vascular events in acute inflammation

A
  • brief vasoconstriction then vasodilation –> increase blood flow
  • increased vascular permeability
  • interstitial edema
  • vascular stasis and congestion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

vascular permeability in acute inflammation

A

endothelial cells become leaky from direct cell injury or via chemical mediators

  • get escape protein rich fluid into interstitium
  • inflammation associated edema
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Endothelial cell contraction

A
  • gap between cells due to endothelial contraction
  • common in venules
  • fast process, short-lived
  • due to vasoactive mediators [histamine, leukotrienes]
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Vasodilation or vasoconstriction in acute inflammation

A

immediately vasoconstriction then vasodilation which leads to greater blood flow to area
- leads to redness [rubor] and heat [calor]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Exudation

A

fluid, proteins, RBCs and WBCs leave intravascular space because of high extravascular - due to osmotic P (∏i) or high hydrostatic P intravascularly [Pc]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Vascular stasis

A

slowing of blood in bloodstream, along with vasodilation and fluid exudation allows chemical mediators and inflammatory cells to collect and respond to stimulus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Endothelial cell retraction

A
  • delayed response, long lived
  • cytoskeletal and junctional reorganization
  • due to cytokine mediators: IL-1, TNF
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

4 Mech of increase endothelial permeability

A
  • endothelial cell contraction
  • endothelial cell retraction
  • direct endothelial injury
  • neutrophil-mediated endothelial injury
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Direct endothelial injury

A
  • endothelial cell necrosis and detachment
  • occurs in severe necrotizing injuries [toxins, burns, chemicals]
  • occurs in venules, capillaries, arterioles
  • causes immediate and long term leakage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Neutrophil-mediated endothelial injury

A
  • mostly in venules, pulmonary capillaries
  • due to neutrophil aggregation, adhesion, and emigration across endothelium
  • – release ROS and proteolytic enzymes
  • – endothelial injury / detachment –> more permeability
  • late response, long-lived
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

3 Steps extravasation

A

extravasation = leukocytes going to site of injury

  1. rolling and adhesion of leukoctyes in lumen
  2. transmigration across endothelium
  3. Migration through interstitial tissue toward chemotactic stimulus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Selectins

A
  • surface molecules that share similar carbohydrate binding domain
  • bind sialyl Lewis-X glycoprotein on cells
  • allow attachment and rolling of neutrophils
  • stimulated by histamine + cytokine to present on cell surface
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

3 Types of selectins

A

P-selectin: platelets, endothelial cells

E-selectin: endothelial cells

L-selectin: leukocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Integrins

A
  • expressed in cytokine stimulated endothelial cells
  • affinity of integrins increased by chemokines
  • – allows firm adhesion of neutrophil to endothelial surface
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

PECAM

A

Platelet endothelial cell adhesion molecule

- involved in migration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Diapedesis

A

Movement of neutrophils through intracellular junctions into interstitium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Neutrophil chemotaxis

A
  • neutrophils migrate along gradient of chemotactic agents in interstitial space
  • chemotactic agents bind receptors on neutrophils and produce secondary messengers
  • –leads to assembly of contractile elements that allows the cell to move via extension of pseudopods
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

4 Neutrophil chemotactic agents

A
  • bacterial products
  • complement fragments [C5a]
  • arachidonic acid metabolites [leukotriene B4]
  • chemokines [IL-8]
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What does neutrophil do once it reaches site?

A
  • phagocytosis of offending agent

- release lysosomal contents and free radicals to interstitium –> chemical tissue destruction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Steps of phagocytosis

A
  • recognition and attachment
  • –opsonins coat antigens and enhance recognition
  • —– Fc of IgG and C3b of complement
  • engulf phagocytosed particule
  • – form phagosome
  • – lysosome fuses with phagosome, form phagolysosome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Neutrophil oxygen dependent bactericidal mech

A
  • triggered by activation nicotinamine-adenine dinucleotide phosphatase
  • – reduces O2 –> O2- –> H2O2
  • myeloperoxidase [MPO] from lysosomal granule converts H2O2 –> HOCL- which kills bacteria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Neutrophil oxygen independent bactericidal mech

A
  • kill bacteria directly by releasing bactericidal permeability-increasesing-proteins, lysozyme, lactoferrin, major basic protein [MBP], eosinophils, argenine-rich defensins
  • killed organisms degraded by hydrolases + other lysosomal enzymes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

myeloperoxidase

A

MPO

  • from lysosomal granules
  • converts H2O2 + Cl- –> HOCL- which is very bactericidal
  • part of oxygen dependent mech
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Neutrophil induced tissue injury

A

during phagocytosis neutrophils release products into phagolysosomes but also into extracellular space

  • lysosomal enzymes
  • free radicals
  • products of arachidonic metabolism [prostaglandins and leukotrienes]

amplifies effects of initial inflammatory stimulus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Macrophages in inflammation

A

clean up everything, migrate away, restore normality of area

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Purulent

A

exudate with prominent neutrophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

suppurative

A

purulent exudate plus tissue necrosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

abscess

A

localized collection of pus [tissue necrosis]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

fibrinous

A

exudate that has fibrin due to proteins leaking from vessels with increased permeability and activation of coagulation cascade

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

ulcer

A

defect on surface of organ or tissue secondary to sloughing off of inflamed necrotic tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

4 Possible outcomes of acute inflammation

A
  • complete resolution: restoration to normal
  • abscess formation: particularly in infections
  • healing by fibrosis [connective tissue replacement] and scarring
  • progression to chronic inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Histamine

A
  • mostly from mast cells plus basophils + platelets
  • prefomed
  • one of first mediators of inflammatory response
  • causes vasodilation and increased vascular permeability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Cell derived mediators of inflammation [2 main types]

A

preformed mediators secreted in granules

    • vasoactive amines [histamine, serotonin]
    • lysosomal enzymes

newly synthesized mediators

    • arachidonic acid metabolites
  • —– cyclooxygenases [prostaglandins + thromboxanes]
  • —–lipoxygenases [leukotrienes + lipoxins]
    • platelet activating factor
    • activated oxygen species
    • nitric oxide
    • cytokines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Serotonin

A

Preformed, in platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What causes mast cells to release histamine

A
  • physical agents [trauma/heat]
  • immunologic rxns of binding IgE Ab to mast cell
  • complement fragments C3a, C5a [anaphylatoxin]
  • neuropeptide [substance P]
  • cytokines [IL1-8, IL8]
  • histamine releasing factors from leukocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Functions of Prostaglandin I2?

A

Prostacyclin

- vasodilates, inhibits platelet aggregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Functions of Prostaglandin E2?

A

Hyperalgesic [makes skin hypersensitive to pain] , vasodilates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Functions of Thromboxane A2?

A

vasoconstrictor, promotes platelet aggregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Functions of Leukotrienes C4, D4, E4?

A

Increase vascular permeability, vasoconstrictor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Functions of leukotriene B4?

A

powerful chemotactic agent

by leukocytes

47
Q

Functions of Lipoxin?

A

Endogenous negative regulators of leukotrienes, inhibit neutrophil chemotaxis, cause vasodilation

48
Q

Inhibitors of cyclooxygenase?

A

aspirin

49
Q

What are cyclooxygenases?

A

prostaglandins + thromboxanes

50
Q

Platelet activating factor

A
  • phospholipid-derived
  • from mast cells [and other leukocytes + EC]
  • Stimulated by IgE mediated rxns
  • function: platelet aggregation, broncoconstriction, vasodilation, increase vascular permeability, leukocyte adhesion, chemotaxis
51
Q

5 Major categories of cytokines

A
  1. Regulators of lymphocyte function
  2. inflammatory cytokines = involved in immunity
  3. Activate inflammatory cells
  4. Chemokines
  5. Cytokines that stimulate hepatopoiesis
52
Q

What are cytokines?

A
  • proteins that modulate function of other cell types
  • Can act on multiple cell types
  • Can be multifunctional with opposing actions
  • Bind specific receptors on target cells
53
Q

3 [2 do the same thing] Cytokines that regulate lymphocyte function

A

IL2 and IL4: favor lymphocyte growth and differentiation

IL1 and transforming growth factor: neg regulation of immune

54
Q

Inflammatory cytokines

A

TNF-alpha, IL-beta
Type 1 interferons [IFN-a and b]
IL6

55
Q

Cytokines that activate inflammatory cells

A

IFN-gamma, TFN-a, IL-5, IL10, IL12

56
Q

Chemokines

A

chemotactic activity for leukocytes

IL-8

57
Q

Cytokines that stimulate hematopoiesis

A

mediate immature leukoctye growth and differentiation

- Il3, Il7, GM-CSF, macrophage-CSF, granulocyte-CSP, stem cell factor

58
Q

IL-1 and TNF

A
  • major inflammatory cytokines
  • act on: endothelium, leukocytes, induction of systemic rxns to acute inflammation
  • produced in macrophages
59
Q

What stimulates secretion of IL-F and TNF

A

Macrophages secrete them when:

- endotoxin, immune complexes, toxins, physical injury

60
Q

Cachexia

A

wasting syndrome

  • due to overproduction TNF-alpha
  • characterized by weight loss and anorexia
61
Q

Endothelial cell activation by ILF-1/TNF

A

stimulate:
- Induction adhesion molec and chemical mediators
- production of enzymes associated with matrix remodeling

62
Q

Hemodynamic effects of septic shock produced by IL-1 and TNF

A

hypotension
decreased vascular resistance
high HR
low blood pH

63
Q

Acute inflammation responses by IL-1 and TNF

A
  • fever, loss of appetite, production sleep

- release neutrophils into circulation, release adrenocorticotropic hormone + corticosteroids

64
Q

3 systems of plasma derived mediators of inflammation

A

3 interrelated systems

  • complement system
  • kinin system
  • clotting factor [Hageman factor] system
65
Q

Hageman Factor

A

Hageman factor = clotting factor XII

  • activated by: neg charge substances on cell surface, bacterial lipopolysaccharides
  • initiates kinin, clotting, fibrinolytic and complement cascades
  • Has chemotactic activity
  • Causes neutrophil aggregation
66
Q

Complement components with inflammatory activity

A
  • C3a and C5a: increase vascular permeability
  • C3b/C3bi: opsonin
  • C5b-9: membrane attack complex
67
Q

Functon of C3a in inflammation?

A

an anaphylatoxin, increase vascular permeability

68
Q

Function of C5a in inflammation?

A

An anaphylatoxin, increase vascular permeability, highly chemotactic to most leukocytes

69
Q

Function of C3b and C3bi in inflammation?

A

opsonin - aid phagocytosis

70
Q

Function of C5b-9 in inflammation?

A
  • Form membrane attack complex

- lyse cells, stimulate arachidonic acid metabolism, produce ROS by leukocytes

71
Q

Kinin system

A
  • generates bradykinin = vasoactive protein

- regulates BP, smooth muscle relaxation/contraction, cell migration, inflammatory cell activation

72
Q

Bradykinin

A
  • vasoactive protein of kinin system
  • formed from plasma kininogens via enzyme kallikrein
  • blood vessel dilator, increases vascular permeability, causes pain
73
Q

What does Kallikrein do?

A
  • enzyme in kinin system
  • forms bradykinin from plasma kininogens
  • part of autocatalytic loop = activator of hagemen factor so amplifies the effect
74
Q

Intrinsic clotting pathway

A
  • series of plasma proenzymes that can be activated by hageman factor
  • activation of thrombin
  • cleavage of fibrin, generation of fibrin clot
  • forms fibrinopeptides
75
Q

Thrombin

A
  • Activated from prothrombin by factor Xa

- Increases leukocyte adhesion to endothelium

76
Q

Fibrinopeptides

A
  • Formed in rxn fibrinogen –> fibrin activated by thrombin
  • induce vascular permeability
  • Chemotactic for leukocytes
77
Q

Chronic inflammation

A

inflammation of wks or months, active inflammation, tissue destruction and attempts at healing all proceeding simultaneously

78
Q

3 main causes of chronic inflammation

A
  • progression of acute inflammation
  • repeated bouts of acute inflammation
  • low grade response does not follow classic acute inflammation [most common]
79
Q

How does acute inflammation lead to chronic inflammation?

A
  • persistent stimulus

- abnormality in healing

80
Q

3 Major cause of chronic inflammation?

A
  • low-grade response does not follow classic acute inflammation
  • – persistent infection by intracellular microbes of low toxicity [TB, viral]

– prolonged exposure to toxic endogeneous or exogenous substances [ silica and silicosis, plasma lipid and atherosclerosis]

– immune rxns against own tissue [autoimmune]

81
Q

3 Characteristics chronic inflammation

A
  • tissue infiltration by mononuclear cells
  • – macrophages, lymphocytes, plasma cells
  • tissue destruction
  • – induced by inflammatory cells
  • attempts at repair
  • – connective tissue replacement, angiogenesis, fibrosis
82
Q

Lymphocyte

A
  • Single nucleus fills most of cell, looks like stand-alone nucleus
83
Q

Plasma cell

A
  • Produces Abs against foreign Ag or altered tissue component
  • Clock face nucleus with adjacent halo pale area from large golgi
84
Q

Macrophage

A

Synonyms: histiocyte, kupffer cell

  • from peripheral blood monocytes
  • activated by cytokines [interferon gamma, T cells], endotoxins
  • secrete toxic substances [ex ROS]
  • cause influx other cells [macro + lymphocytes]
  • cause fibroblast proliferation + colllagen deposition
  • phagocytosis
85
Q

Mast cell

A
  • found in connective tissue
  • express receptors that bind Fc portion of IgE
  • in acute response: Ag recognition –> histamine release
  • – part of anaphylactic rxn to allergens
  • some parasite infections also increase IgE and mast cell activation
86
Q

Eosinophil

A
  • immune rxn mediated by IgE and parasites
  • recruitment of eotaxin [a chemokine]
  • granules contain major basic protein [MBP] that is toxic to parasites and epithelial cells
87
Q

Factors secreted by macrophages

A
  • neutral proteases
  • chemotactic factors
  • arachidonic acid metabolites
  • ROS
  • complement components
  • coagulatin factors
  • growth factors
  • cytokines [IL-1 and TNF]
  • others [PAF and alpha-IFN]
88
Q

Granulomatous inflammation

A

characterized by

  • collections of epithelioid macrophages surrounded by collar of mononuclear leukocytes [mostly lymphocyte, some plasma]
  • central necrosis may be present

2 types: foregin body, immune

Occurs in TB, sarcoid, leprosy

89
Q

Epithelioid macrophage

A

activated macrophage that has epithelial like appearance

90
Q

Immune Granuloma

A

Formed by T-cell mediated rxn to Ag that are hard to degrade
- prototype = TB

May have central necrosis [necrotizing granuloma]
- caseous necrosis

91
Q

Foreign body granuloma

A

Caused by inert foreign bodies

ex. suture granulomas

92
Q

3 Outcomes of chronic inflammation

A
  • resolution/regeneration to normal
  • – requires removal toxic agent, cells able to regenerate, intact stromal frame
  • reapire/organization/healing by connective tissue/fibrosis/scarring
  • idenfinitely occuring [ex. rheumatoid arthritis]
93
Q

Requirements for chronic inflammation to resolve to normal

A
  • removal toxic agent
  • cells able to regenerate
  • intact stromal framework
94
Q

How to tell acute vs chronic inflammation [time frame, cell types, pathogenesis, cause, outcomes, treatments]

A

time frame: acute = short, chronic = long

components: acute = neutrophils, chronic = lymphocytes + macrophages
pathogenesis: acute = vasodilation + vascular permeability, chronic = cytokines/chemokines attract lymphocytes + neovascularization
cause: acute = infection or burn, chronic = prolonged exposure to toxic agent
outcomes: acute = resolution or abscess or scarring or become chronic, chronic = regeneration or scar formation or resolution

95
Q

What should you look for in histology of tissue undergoing repair?

A
  • granulation tissue

- brining in fibroblasts to form scar

96
Q

What should you look for in histology of tissue undergoing regeneration?

A
  • mitotic figures

- hyperplasia

97
Q

Granulation tissue is a sign of what?

A

repair

- composed of proliferating capillaries + cells [fibroblasts, macrophages, etc] within loose connective tissue

98
Q

What is etiology of rheumatoid arthritis?

A

AA amyloids from precursor SAA protein

99
Q

What histologically shows you there is cirrhosis of the liver?

A

presence of fibrous septa that subdivide parenchyma into disorganized regenerating nodules

100
Q

If you see liver nodules, think what condition?

A

cirrhosis!

101
Q

predominant cell type in acute inflammation

A

neutrophils

102
Q

3 chemotactic agents for neutrophils

A
  • leukotriene B4
  • C5a/C3a
  • cytokines [IL-8]
103
Q

2 chemical mediators of systemic acute phase response

A

TNF-alpha

IL-1

104
Q

What stimulates selectins?

A

histamine and cytokines

105
Q

What 2 cytokine mediators induce endothelial cell retraction?

A

IL-1

TNF

106
Q

Is endothelial cell contraction or retraction longer liver? Which happens first?

A

endothelial cell contract is first

endothelial cell retract lasts longer

107
Q

Among the 4 mechanisms of increased vascular permeability, which are short/long lived and which are immediate/delayed?

A

neutrophil mediated endothelial injury: late, long lived
direct endothelial injury: immediate, long term
endothelial cell contraction: immediate, short lived
endothelial cell retraction: late, long liveed

108
Q

What are the functions of IL-1 and TNF

A
  • systemic acute phase response
109
Q

Where does endothelial contraction usually occur?

A

venules

110
Q

What produces leukotrienes?

A

lots of cells?

111
Q

Where does neutrophil mediated endothelial injury occur?

A

mostly in venules, pulmonary capillaries

112
Q

What is a function of IL-2 and IL-4?

A

favor lymphocyte growth and differentiation

113
Q

What cytokine is associated with cachexia?

A

TNF-alpha

Pathology (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions