Chapter 2 Flashcards
(149 cards)
1
Q
Inflammation is a ______ response to injury
A
vascular
2
Q
Actions of inflammation
A
- kills and eliminates infective microbes
- removes cellular debris: injured cells/tissues
- initiates tissue repair
3
Q
Leukocytes last ______ in circulation
A
4 days
4
Q
Lymphocytes are granular or agranular?
A
Agranular
5
Q
Monocytes are granular or agranular
A
Agranular
6
Q
Neutrophils
A
granular WBCs associated with acute inflammation and allergies
7
Q
Eosinophils
A
Granular WBCs associated with allergies
8
Q
Basophils
A
Granular WBCs
Associated with Parasites
least numerous
produce heparin
9
Q
2* tissue damage caused by inflammation can occur in what 3 situations discussed in class?
A
- highly virulent mic robes (HIV, TB)
- Prolonged/chronic infections
- inappropriate immune response
10
Q
injury or infection is detected by what 3 cell types?
A
macrophages, dendritic cells, mast cells
11
Q
5 steps of inflammation
A
- Recognize the injury/microbe
- Recruit leukocytes
- Remove agent (via phagocytosis)
- Regulate (control) response
- Resolution and repair
12
Q
5 cardinal signs of inflammation
A
Rubor (redness), Calor (heat), Tumor (swelling), Dolor (Pain), Functio laesa (loss of function)
13
Q
Self-limiting inflammation is described as…
A
pro-inflammatory mediators are inactivated
anti-inflammatory mediators are activated
14
Q
Acute Inflammation
A
rapid onset, local and systemic signs (edema, rubor, ect.), neutrophils present, no fibrosis
15
Q
Chronic Inflammation
A
insidious onset, few systemic signs, angiogenesis and fibrosis present
Macrophages, lymphocytes and plasma cells
16
Q
How does Graston and similar therapies help with chronic inflammation?
A
Reintroduces controlled trauma which moves trauma from chronic state into acute state
17
Q
2 major components of acute inflammation
A
vascular changes
leukocyte recruitment and activation
18
Q
how do cells recognize harmful agents?
A
pattern recognition receptors
macrophages, dendritic cells, mast cells
recognize molecular patterns that are “non-self”
19
Q
Toll-like receptors (TLRs)
A
recognize all types of infectious pathogens
located on the plasma membrane
20
Q
Inflammasome
A
recognizes products of dead cells (uric acid, ATP) and crystals
located in cytoplasm
21
Q
How can vessels alter themselves?
A
caliber, blood flow, permiability
22
Q
3 vascular changes associated with inflammation
A
- Vasoconstriction (few seconds only)
- Vasodilation (rubor)
- Increases permeability
23
Q
Margination
A
collection of WBCs along the vascular walls
24
Q
migration of WBC
A
Diapedesis
movement of cell from point A to point B (inside vessel –> outside vessel)
AKA: transmigration, extravasation, emigration
25
Increased permeability causes this by reversing the osmotic gradient, allowing fluid to collect in the interstitial spaces?
Edema
26
Mechanisms for increased permeability in vessels (3)
1. endothelial contraction
2. endothelial necrosis
3. leakage from angiogenesis
27
Endothelial contraction
Most common
Histamine binds leaving gaps in postcapillary venules
lasts for 15-30 min after acute inflammation
28
Endothelial necrosis
causes leakage in postcapillary venules until the vessel is repaired
caused by burns, severe infections, irradiation
29
Leakage from angiogenesis
new vessels have immature (leaky) endothelial cells
| occurs during tissue repair and tumor growth
30
Exudate
Protein-rich
31
Transudate
Protein-poor
32
Edema occurs because...
lymphatic drainage cannot keep up
33
Lymphadenopathy
general disorder of the lymphatic system
34
lymphadenitis
Inflamed lymph nodes
35
Lymphangitis
Inflamed lymphatic channel
36
4 steps in leukocyte recruitment
1. margination and rolling
2. firm adhesion to endothelium (pavementing)
3. transmigration between endothelial cells
4. chemotaxis toward target tissue
37
Leukocytes migrate via....
pseudopodia
38
Neutrophils are replaced by macrophages and lymphocytes after being killed via apoptosis within __ hours.
48
39
opsonins
```
immunoglobulin G (IgG), complement
enhance macrophages binding and breakdown
"marked for death"
```
40
Leukocyte-induced tissue injury
2* tissue injury
once activated, WBCs don't distinguish
causes damage via ROS and enzymes
Secrete cytokines
41
3 common opportunities for leukocyte-induced tissue injury
1. persistent infections (TB, VZV)
2. complication of ischemia (ischemia-reprofusion injury)
3. Hypersensitivity reactions (allergies, autoimmune conditions)
42
3 Outcomes of Acute Inflammation
1. Resolution
2. Chronic Inflammation
3. Scarring
43
Resolution of Acute inflammation
Regeneration and repair
| normalization of vessel permeability, WBC apoptosis, Lymph drainage, angiogenesis, restored structure
44
Chronic inflammation as an outcome of acute inflammation
caused by failure to remove offending agent
severity of damage and cellular regeneration capacity
either restored or scarred
45
Scarring after acute inflammation
FIbrosis
Severe tissue damage, unable to regenerate
Filled with connective tissues = decreased function
46
Serous inflammation
serum accumulation within or below the epidermis
watery effusion
produces a blister: burn, virus
47
Fibrinous inflammation
```
severe injury, Increase vessel permeability, allows large molecules out of circulation, produce fibrin-rich exudate
Severe fibrosis (adhesions)
```
48
Suppurative inflammation
Purulent
local infection with a pus-forming organism (Staph. aureus)
produces abscesses
49
Abscess
focal collection of pus
50
Pus contains...
neutrophils, necrotic cells, edema
51
Ulcerative Inflammation
local tissue necrosis on tissue surface, defect follows sloughing of necrotic tissue
peptic ulcer, aphthous ulcer
52
pseudomembranous inflammation
caused by Corynebacterium diphtheria, Clostridium difficile
53
Granulomatous inflammation
produces a granuloma
54
Condition which causes caseating granuloma?
Tuberculosis (TB)
55
Mediator of inflammation that we talked about in class
Arachidonic acid metabolites from WBCs, Mast cells, endothelia, & platelets
56
Prostaglandins
Arachidonic acid metabolite that causes vasodilation, pain and fever
57
NSAIDs effect on prostaglandins
block prostaglandin synthesis (anti-inflammatory)
58
3 characteristics of chronic inflammation
1. mononuclear leukocyte cells
2. tissue destruction and fibrosis
3. vessel production (angiogenesis) and repair
59
2 types of macrophage activation
Classic (M1) and Alternative (M2)
60
Classic (M1) Activation
Microbes, endotoxins, active T cells, cytokines, crystals, dead cell particles
ROS --> microbial actions: phagocytosis & killing of many bacteria
Cytokines --> inflammation
61
Alternative (M2) Activation
cytokines, mast cells, eosinophils
| non-microbial: tissue repair, fibrosis, anti-inflammatory effects
62
4 systemic effects of inflammation
Acute-phase reaction, Leukocytosis, Leukemoid reactions, Leukopenia
63
Acute-phase reaction
charactarized by lethargy, somnolence, malaise, increased HR, increased BP, anorexia, anhidrosis
produces fever & elevated plasma proteins
64
Fever caused by:
pyrogens --> prostaglandin synthesis
tells the hypothalamus to increase the temperature set point
65
Elevated plasma proteins
increased cytokines produces increase hepatic synthesis of proteins (C-reactive protein [biiomarker for inflammation], fibrinogen)
causes increased Erythrocyte Sedimentation Rate (ESR)
66
Leukocytosis
increased blood leukocyte count
common with bacterial infections
15-20K/ul, increase immature cells "shift to left"
67
Bacterial leukocytosis is characterized by an increase in ___.
neutrophils
68
Viral leukocytosis is characterized by an increase in ___.
lynphocytes
69
Leukemoid Reactions
extremely high blood leukocytes count (40-100k/ul)
mimics leukemia
caused by chronic inflammation (TB, Clostridium difficile)
70
Leukopenia
Decreased blood leukocyte count (>4000)
71
What are the 2 causes of cardiac fibrosis?
1. Ischemic Necrosis (myocardial infarction)
| 2. Possible ischemia-reprofusion injury
72
A mild/transient injury can be regenerated to a "pre-injury status". True or false?
True
73
Prolonged injury:
cells are unable to divide, cannot be restored to "pre-injury status"
leukocytes, angiogenesis, granulation tissue
scar formation
74
Two types of cellular proliferation
physiologic and pathologic
75
physiologic cellular proliferation
well-regulated, repairs injury tissues, adaptations to stress, preserves normal cellular functions
76
Pathologic cellular proliferation
unregulated proliferation, result of genetic alterations, neoplasia
77
GFs promote cell shift from G1 phase to G2. True or false?
False. G0 -->G1
promote entry into the cell cycle
78
Cyclins
regulators of the cell cycle
79
2 types of cyclins
Cyclin-dependent kinase (CDK) enzymes
| Cyclin-dependent kinase inhibitors (CDKIs)
80
CDKIs effect on the cell cycle
slows it down
81
GFs effect on CDKIs
suppression
pushes cell through the cycle
82
3 types of proliferative capacity
labile, stable, permanent
83
Labile cells
continuously dividing, continuously lost and quickly regenerated
i.e., epithelia & hematopoietic cells
84
Stable cells
in quiescent state
limited replication (usually only in response to injury)
i.e., solid organs (kidney, liver, pancreas)
85
Permanent cells
terminally differentiated cells
injury is irreversible & highly disabling
CNS neurons, skeletal & cardiac muscle, old cells (near Hayflick limit)
86
Hayflick Limit
limited number of times the cell can divide before its done... really old cells
they die when they reach it
87
most tissues have what proliferative capacity??
combination of all 3!
88
properties of stem cells
self-renewal capacity (undifferentiated)
| asymmetric replication
89
asymmetric replication
some cells differentiate, other remain undifferentiated
keeps producing more stem cells during division
90
GFs function during regeneration & healing
1. stimulate growth control genes
2. ignore cell cycle checkpoints
3. prevent apoptosis
91
GFs are produced by what 2 cells at the site of inflammation?
Macrophages & lymphocytes
92
Autocrine GF signaling
GFs act on the secreting cell (rare)
93
Paracrine GF signaling
GFs act on the cells adjacent to the secreting cell
94
Endocrine GF signaling
systemic, via circulatory system
95
GFs are normally produced where?
Anterior pituitary gland
96
Mitogen
increases cell proliferation
| Pituitary growth hormone is an example of this
97
Extracellular matrix is characterized by:
network of proteins
structural support - "scaffolding" for tissue repair
constantly remodeling
98
Other functions of Extracellular matrix
storage of water, minerals, GFs
| regulation of cell proliferation and movement
99
2 types of ECM
Interstitial matrix
| basement membrane
100
interstitial matrix
between cells in connective tissues
3D gel with no specific shape
produced by fibroblasts
101
basement membrane
Surrounds cavities & organ surfaces
"chicken-wire" mesh
produced by epithelium
102
3 components to ECM
fibrous proteins
water hydrated gels
adhesive glycoproteins
103
fibrous proteins in ECM
collagen: tensile strength, triple helix, scars
| elastin, recoil, arteries, skin, ligaments, etc
104
water-hydrated gels in ECM
resilience, lubrication
Hyaluronan: binds water, gel-like
Proteoglycans: compressibility, GF storage
105
Adhesive glycoproteins in ECM
connect elements of ECM to other cells (cellular adhesion)
| fibronectin, laminin, integrins, selectins
106
ECM functions
```
Mechanical support (scaffolding) for repair
Regulation of cellular proliferation
```
107
Scaffolding for repair
increased disruption in ECM increases fibrosis
108
Regulation of Cellular proliferation
storage & quick deployment of GFs
regulates cellular differentiation
integrins create firm adhesion, endothelial transmigration
109
Ability to replace injured tissues is dependent on what 2 factors?
1. cell's inherent capacity to proliferate
| 2. severity/nature of injury (extent of ECM & stem cell damage)
110
Compensatory growth
Stable cells
| R kidney can grow bigger if L kidney is damaged or removed
111
hepatocytes
have a unique capacity to heal
| good in case you need a liver transplant, living donor can give a lobe and survive
112
Steps of Scar formation
1. angiogenesis
2. fibroblast migration & proliferation
3. collagen deposition --> scar
4. remodeling (lifetime)
113
Within 24 hours of injury...
fibroblasts accumulate, endothelia begins repair
114
Within 3-5 days...
granulation tissue appears
| contain fibroblasts, capillaries, connective tissue, WBCs
115
Formation of new vessels
capillaries spout from existing vessels
| endothelial precursor cells (EPCs) from marrow
116
angiogenesis vie pre-existing vessels
limited to site of injury
117
Vasculogenesis
EPCs = endothelial precursor cells (angioblasts)
118
Scar tissue deposition in relation to granulation tissue
scar tissue is built upon granulation tissue
119
2 steps of scar tissue deposition
1. fibroblast migration to site of injury
| 2. deposition of ECM irregular collagen
120
originally, scar tissue is ___ in vascularity
high
121
progressively, scar tissue ___ in vascularity
decreases
122
Remodeling of connective tissue
ECM continues to be remodeled causing a balance between ECM synthesis and breakdown
123
Matrix Metalloproteinase (MMPs) are produced by:
fibroblasts, macrophages, neutrophils, and endothelial cells
124
MMPs breakdown ___
collagen
125
MMPs require
zinc as a cofactor
126
MMPs are regulated by
TIMPs (tissue inhibitor of metalloproteiinases)
127
Factors influencing repair
infection, nutritional deficiency, glucocorticoids (steroids), poor profusion, etc.
128
Infection influence on repair
prolongs inflammation, leukocyte-induced tissue injury
129
Nutritional deficiency influence on repair
Vitamin C
| decrease basement membrane = vessel fragility
130
Glucocorticoids (steroids) influence on repair
anti-inflammatory, decrease fibroblast activity
131
Poor profusion influence on repair
decrease arterial supply, decrease venous damage
132
Keloid
scar tissue beyond boundaries of wound caused by excessive collagen deposition and exuberant granulation tissue
133
keloids are characterized by:
raised flesh colored scars that do not regress and get worse following excision
134
Deeper injuries to dermis increase or decrease risk of keloids?
increase
135
healing of skin wounds is a combination of:
epithelial regeneration and fibrosis
136
Phases of healing which overlap
1. inflammation
2. formation of granulation tissue
3. ECM deposition & remodeling with possible wound contraction
137
Healing by first intention (primary union)
incision, sutured
small wound, few cells die
minimal fibrosis, minimal wound contraction
138
Day 1 primary union
clot formation
139
Day 3 primary union
granulation tissue
140
Day 5 primary union
peak angiogenesis, collagen bridges the wound
141
1 month primary union
inflammation is absent, epidermis is essentially normal
142
Healing by second intention (secondary union)
large wound, intense inflammation with possible 2* tissue injury
large clot/scab and abundant granulation tissue
prominent wound contraction via myofibroblasts
143
timeline for secondary union
more than 6 weeks
144
sutures are removed after...
1 week
145
at 1 week post suture, wound is __% of normal strength
10%
146
increased wound strength over 1st month to around...
70%
147
Strength of wound is at max around 3 months: up to __%
80%
148
Scar remodeling is a process of making the wound less prominent and can take....
several years, basically forever...
149
triggering of the inflammasome results in activation of what enzyme?
Caspase-1
