Inflammation and Repair Flashcards
1
Q
inflammation
A
the response of vascularized tissue to injury
2
Q
acute inflammation (2 important things)
A
steryotyped, after the INITIAL vasoconstriction:
Vessels dilate (histamine, etc.) vessels leak protein (histamine etc)
3
Q
RUBOR
A
red - from vessel dilation
4
Q
CALOR
A
hot - from vessel dilation
5
Q
TUMOR
A
swelling - grom leaky vessels
6
Q
Vessels leak protein in acute inflammation
hurt a little
hurt worse
hurt really bad
A
-
albumin comes out
IgG comes out
fibrinogen/fibrin for mesh comes out
7
Q
Neutrophils in acute inflammation
A
pass through the venues and damage anything they think may be bacteria and whatever tissue is nearby
8
Q
DOLOR
A
pain
9
Q
Chronic inflammation
A
orchestrated by T cells mostly
B cells become plasma cells and make antibodies
Macrophages gobble things up, if they get mad–> form walls=granulomas
eosinophils kill worms
10
Q
Granulation tissue
A
fibrin meshwork if not destroyed by plasmin will be ORGANIZED into granulation tissue
by endothelial cells and fibroblasts
macrophages eat the firing, endothelial cells make new vessels, and fibroblasts make collagen fibers
at the end, fibroblast grow contractile fibers like little muscles and this is how SCAR CONTRACTS
11
Q
myofibroblasts
A
cause scars to contract
12
Q
Band cell
A
immature neutrophil. child soldier, baby neutrophyl
13
Q
lymphocyte
A
dense chromatin
14
Q
monocyte
A
dent in nucleus. name changes to macrophage as soon as it leaves the bloodstream
15
Q
neutrophil
A
segmented nucleus. made daily just to protect and help you
16
Q
eosinophil
A
pink
17
Q
basophil
A
blue
18
Q
the _____ are the commandos of acute inflammation
A
neutrophils
72 hour life span, clear, packed up on glycogen. Rambo on sugar. can burn up fuel source because they may move to a place where they don’t have access to other nutrients.
segmented nucleus so they can squeeze into places other cells can’t and they can do it fast
19
Q
diapedisis
A
transmigration of neutrophils through a blood vessel in a combat zone. takes place primarily in venues - because they have a low flow rate and aren’t as fragile as capillaries
20
Q
Neutrophils are heavily armed troops with a variety of weapons in various
A
granules
21
Q
azurophil granules
A
myeloperoxidase, elastase, cathepsins
22
Q
specific granules
A
alkaline phophatase, lactoferrin, and collagenase
23
Q
both granules have
A
lysozyme
24
Q
Myeloperoxidase
A
a heme based protein that produces hypochlorite like in household bleach
H2O2–> OCl-
25
myeloperoxidase deficiency/absence
people without it can still kill germs fine, they have other potent weapons
26
ongoing inflammation makes neutrophils
stick better to the endothelium (selections and integrins)
| get through endothelium
27
Deficiencies in selectins, integrins and ligands
WBC adhesion defects - can be bad
28
Gonococcal infection of the finger
the redness from extra blood flow through dilated arteries (HYPEREMIA). One joint inflamed, gonorrhea until proven otherwise
29
All human tissue is gram
negative
30
pus
liquid composed of neutrophils and the body tissues their enzymes have liquefied during combat
31
adjective for pus
purulent
32
verb for make pus
supperate
33
pus surrounded by mor normal tissue
abscess
34
puss filing a body cavity (pleural space, gall bladder)
empyema
35
gonorrhea can cause
purulent urethritis
| fatal infections of joints
36
neutrophils lose their ____ after death
segmentation
37
in health and illness, neutrophils tend to stick to
vessel endothelium= marginate
38
aside from neutrophils, you may see ___ in pus
fibrin strands
39
pus builds up pressure because
osmotic pull of the small molecules produced by hydrolysis of big proteins
40
pus is yellow because
necrosis is yellow - lipid goes out of the aqueous phase
41
greenish tinge on exposure to air (of pus)
due to neutrophil myeloperoxidase
42
pseudomonas infections
fluorescent green pus that smells like grapes
| pigment= pyocyanin
43
clostridial infections
thin (hydrolyzed) gray (lipolyzed) dishwater pus
| [clostridia cause your body to decompose, tear up proteins, everything]
44
left shift
lots of band cells, lots of child neutrophils. something bad is probably going on
45
Leukemoid reaction (what you find in blood)
severe infection where so many neutrophils including young ones may be present in the blood that you'll suspect leukemia
>50,000 WBC in the absence of true leukemia. in leukemia the wbcs probably aren't powered up. no toxic granulation
46
toxic granulation
powered up neutrophil. more active. something bad probably going on.
47
leukemoid reaction will have
high leukocyte alkaline phosphatase (low in leukemia)
usually toxic granulation
will lack the chromosome markers for leukemia
48
if in doubt of leukemia reaction vs leukemia
treat for infection. leukemia can wait for days. if the la testing leaves the diagnosis uncertain, do a history and physical exam
49
Systemic inflammatory response
current term for multiple organ failure developing as a result of a bad infection.
extreme elevations of IL-1 and TNF-a.
Once its underway, treating the cause may not save the patient
50
first line of defense agains the bacteria we meet as we go through life
neutrophils
51
staphylococci
try to sequester themselves from their principal enemies (the neutrophils)
52
streptococci
try to outrun neutrophils
53
necrosis always attracts some
inflammatory cells early on
54
Neutrophils in the lung - damaging effects
good that they are there to help, but can --> no air in the lungs--> death
55
Chediak Higashi features
problems with organelles (lysosomes, melanocytes) and thus impaired neutrophil killing of microbes
56
Chronic Granulomatous disease
any of several defects in neutrophil killing of common staph
the body walls off staph using granulomas instead. trivial skin lesions turn into long standing TB-like lesions; if staph get access to lungs death can result if unrecognized
57
Exudate
potein rich fluid released from vessels in inflammation.
in acute inflammation, blood vessels dilate and leak protein, and neutrophils come to the scene
58
friction blister
epidermis detached from the dermis. mild inflammatory cellular reaction
59
ROS
reactive oxygen species, free radicals
| need these to kill germs. this may be one reason that antioxidants do so poorly as health promoters in real studies
60
Neutrophils self destruct after _____. if needed, they can turn into ______
72 hours
| traps that bind nearby bacteria (neutrophil extracellular traps, NETS)
61
Sunburn
cells that recognize themselves to be radiation-damaged undergo apoptosis
apoptosis of endothelial cells causes vasodilation and delayed-prolonged leakage (causes capillaries to relax)
peeling= desquamation
62
special reasons for vessel dilation
ie sunburn, where the 'molecular and cellular mediators of inflammation' aren't even involved
63
Triple Response of Lewis
1. local redness (capillaries dilate)
2. flare surrounding the scratch (capillaries dilate)
3. swelling/edema (a wheal) surrounds the scratch
only the flare depends on an intact nerve supply. This led to the discovery of histamine, the first known inflammatory mediator
64
Histamine (released from, and functions in inflammation - 3)
major mediator, released from mast cells. functions in inflammation:
dilate blood vessels
make them leaky to proteins, especially albumin
may contribute to pain and itching
bronchoconstriction and a host of other effects
65
Seratonin
in small amounts is released from platelets and constricts vessels (help us stop the bleeding, thanks)
not a targetable factor in what we usually call inflammation
its role in emotional health completely overshadows this
66
Bradykinin
inflammatory peptide that famously DILATES vessels, at least partly by producing prostacyclin.
mediates som pain of inflammation
also a bronchoconstrictor and inflames the airwaymucosa.
67
Bradykinin production
produced in the blood by the kinin-kallikrein system.
68
Brady kinin and ace inhibitors
ace inhibitors famously interfere with the breakdown of bradykinin, which explains the cough side effect (bronchoconstriction and inflamed airway mucosa are effects of bradykinin)
69
prostaglandins and trhomboxanes are made from _____ by means of _____.
arachidonic acid
cyclooxygenase
COX can be inhibited by a variety of medications
70
Prostaglandin E2
variety of effects in acute inflammation
| FEEEver, making vessels permeable, and making vessels dilate
71
PGD2
making vessels permeable
| making vessels dilate
72
porstacyclin
PGI2,
| inhibits platelet aggregation and dilates blood vessel (keep blood vessels open for troops)
73
Thromboxane A2
promotes platelet aggregation and constricts blood vessels (lets not have a hemorrhage right now troops)
74
When COX is inhibited, AA gets sunned into the _____ path instead. Favoring production of ______
lipo-oxygenase pathway
other mediators, especially by neutrophils and macrophages
leukotriene B4, Leukotrienes C4 D4 and E4
75
leukotriene B4
famous promotor of neutrophil attachment and chemotaxis
76
Leukotrienes C4, D4, and E4
constrict vessels, make them permeable, and constrict airway smooth muscle. there are medications for asthmatics that block their action
77
5-HETE produced by _________ via the _____ pathway is a __________
neutrophils and lymphocytes
lypooxygenase pathway
chemotactic agent
78
Lipoxins
made via lipooxygenase pathway
produced by neutrophils and macrophages when inflammation is about to end
"brakes"
79
C3a
fragment of complement that is a powerful chemotactic agent
80
C3b
fragment of complement that binds to microbes via antibodies and allows more complement activation nearby as well as promoting opsonization and thus phagocytosis
81
C5a
powerful promotor of inflammation (KING OF THE CASCADE)
promotes chemotaxis
makes more adhesion molecules on endothelium
makes vessels dilate
makes vessels leak
82
MAC
produced at end of complement cascade, punches holes in membranes
83
IL-1
family of cytokines produced mostly by MACROPHAGES, but also other cells
mostly powerful pro inflammatory cytokine
Fever (endogenous pyrogen)
increased neutrophil production
increase in adhesion molecules
increased movement of and killing by phagocytes
recruitment of lymphocytes to sites of inflammation
causes fatigue and increased sensitivity to pain
dilates blood vessels
increases insulin resistance, changes protein production by liver (acute phase reaction
84
Anakinra
blocks IL-1Ra, works agains rheumatoid arthritis
85
IFN-g
made by T cells mostly, is another strong pro inflammatory cytokine
recruiting neutrophils and macrophages to sites of inflammation
activating macrophages and making them more deadly
making cells produce more IL1, IL12, and IL23
used for chronic granulomatous disease and osteopetrosis
86
used for chronic granulomatous dz and osteopetrosis
IFN-g
87
IL-2
cytokine that has little to do with inflammation, but seems to regulate whether T cells respond to antigens or tolerate them
as a recombinant medication, its in use against malignant melanoma and renal cell carcinoma
88
A form of IL-2 complexed with diphtheria toxin is used
against cancer cells that express the IL2 receptor, most famously some cutaneous T cell lymphomas
89
IL-4 and IL-13
antiinflammatory. produced by macrophages, direct other macrophages to produce anti-inflammatory mediators
TGF-b and IL-10
Alternatively activated macrophages
90
M2 macrophages produce
TGF b and IL10 as well as
| osteopontin - granuloma glue - lets not fight, but wall it off instead
91
IL-5
from Th2 and mast cells
attacts and activates eosinophils.
may use an antibody against Il5 to treat type I allergen illness, esp in severe asthma
92
IL-6
some effects similar to IL-1 (fever, neutrophil production)
some anti-inflammatory
the one major cytokine produced by skeletal muscle and is increased by exercise. from sk m= anti-inflammatory
credited for much of the acute phase reaction, with changes in the levels of proteins made by the liver for the blood stream
93
IL-12
from stimulated dendritic macrophages and stimulated B cells
turns undifferentiated Tcells into Th1 cells and causes Tcells to produce IFN-g and TNF-a
powerful pro inflammatory effects and is among usual suspects in various autoimmune diseases
94
IL-23
up and com ing molecule with effects that may have previously been attributed to IL-12
95
IL-17
produced by Th17 promote recruitment of neutrophils, macrophages, and mor Th17 cells to sites of inflammation
famously bad actor that is everywhere
main suspects in rheumatoid arthritis, inflammatory bowel disease, and psoriasis
96
TNF
```
produced by macrophages and by many other cells.
proinflammatory
causes fever ('endogenous pyrogen')
causes neutrophil production
activates neutrophils and macrophages
helps mediate the acute phase reaction
promotes thrombosis
promotes insulin resistance
induces apoptosis
```
97
TNF is worth knowing bc
its used as an immunostimulant itself.
medicines that block its receptor are among the most important meds for asthma, rheumatoid arthritis, anklyosing spondylitis, inflammatory bowel did, psoriasis and others
TB and fungal infections are the chief risks of these meds
98
PDGF
produced by platelets and other mesenchymal cells
powerfully promotes growth of NEW VESSELS as in granulation tissue/young scar
use to treat ulcers, and by surgeons and periodontists
99
TGF-b
produced by many cells including macrophages
LAYING DOWN SCAR, sometimes great, sometimes not
seems to be key to effective collagen production in scar, and is blamed for fibrosis in chronic inflammation
slows inflammation, promotes fibrosis and restoration of damaged epithelial cell populations, and can turn other T lymphocytes into t suppressor cells
100
Platelet activating factor
small molecule with several known or suspected actions in inflammation
101
chemokines
peptides that get neutrophils moving faster when needed
102
C-reactive protein and SAA protein
produced by liver in response to the acute phase reaction
CRP has become a pop blood test that supposedly is one more coronary risk factor. some clear value in rheumatology
SAA is protein that is often B pleated to amyloid in the presence of chronic inflammation (leprosy famously)
103
Results from mutations in relatively obscure molecules that act as brakes, or gain of function mutations in cytosine receptors
several auto inflammatory diseases. the most familiar is FAMILIAL MEDITERRANEAN FEVER, which can mimic almost anything
104
Neutrophil monocyte topics
```
adhesion
margination
opsonization
chemotaxis
chemokines
phagocytosis
degranulation
microbe killing
whats in what sort of neutrophil lysosomal granule
```
105
common clinical problems interfere with neutrophil function in a variety of ways
ie diabetes, glucocoritcoid rxs
106
Acute phase reaction
quantities of various proteins in the plasma change when significant inflammation has been going on for a while
RBC sink faster in the plasma= increased erythrocyte sedimentation rate
107
anemia of inflammation
changes in one's chemistry also result in less uptake of iron by developing red cells. that will appear if this goes on for very long (part of acute phase reaction)
108
neutrophils
classic bacterial infection, candida, bad injury
109
lymphocytes
autoimmunity, viruses, pertussis
110
monocytes
mycobacteria, other fungi, typhoid
111
eosinophils
worms, asthma, hodgkins's, dermatitis, herpetiformis, dermatomyositis, IgE allergy less often
112
plasma cells/activated B cells
especially abundant with spirochetes (syphilis, Lyme dz)
113
no inflammatory cells
prions, gas gangrene (very aggressive clostridia), the immunocompromised
114
Eosinophil granules are specialized for
chemical warfare against worms, their intended target
| extremely alkaline granules (major basic protein) - pour base all over worms
115
Lymphocytes with nuclear dent is often a
T killer cell
116
plasma cells
nucleus is always pushed to one side of the ell. clock face/soccer ball nucleus
117
the harness of a chancre, the lesion of primary syphilis is due to the great abundance of
mostly plasma cells
118
A circulating monocyte/mononuclear phagocyte
dent in the nucleus. changes its name to macrophage when it leaves the bloodstream
119
ink used to make tattoos
more or less fixed macrophages contain the ink
| macrophages loaded with pigment
120
____ come first, ____ move in later on
neutrophils (24hrs)
| monocytes/macrophages
121
macrophages, can _____
stick tight together
122
How our body rids itself of splinters
epithelium does not tolerate a free edge, so it grows along the splinter
macrophages adhere to the splinter and to one another, forming a granuloma
123
Macrophages stuck tight together form a
granuloma
| they are called epitheliod, by sticking together they mimic epithelium
124
Histoplasmosis
KC
| histoplasmosis granuloma with caseous center
125
foreign body giant cells are
fused clusters of macrophages with nuclei distributed throughout
126
Langhans cell
is fused macrophages with nuclei in a horseshoe around the edge
127
Most foreign bodies end up surrounded by
granulomas
128
TB
caseating granuloma
129
giant cell with asteroid body
altered cytoskeleton, but no one know whether it means anything
130
The sealant on your own abrasion
fibrin
131
fibrous means
collagen
132
fibrous means
fibrin
133
Ulcer
the epithelium and a significant amount of connective tissue underneath have been lost to necrosis
ulcer is a portion of epithelium plus at least some underlying CT that has been lost to necrosis
the crater of an ulcer is always inflamed and fibrin sealed
134
Erosion
loss of epithelium WITHOUT significant damage to the underlying CT. in a stomach erosion, only the epithelium and a bit of the lamina propria are gone
135
pseudomembrane
very broad, very shallow ulcer. seen famously in diphtheria and C. difficult colitis
136
Scab
fresh clot - just a scratch
factor XIII crosslinks fibrin. vessels and fibroblasts invade the fibrin meshwork
ready to fall off - immature scar tissue below
will fill it in with fibrin. the soft clot becomes harder after a few hours. factor XIII cross linking the fibers. red gell stuff under a scab - granulation tissue - fibrin that's been grown into by the fibrobasts
137
Granulation tissue
fibrin that's been grown into by epithelial tissue, vascuature. gribroblasts
138
scar
is collagen
139
Law of epithelium
epithelium does not tolerate a free edge. if an epithelial cell is missing a neighbor on one side, it divides to replace it.
everybody wants a neighbor
140
healing skeletal muscle fiber
purply RNA rich cytoplasm and big, active nuclei with a whole lot of euchromatin
141
new collagen laid down at site of healing injury
scar
142
if you damage the CT below lamina propria,
you'll get at least a tiny scar afterwards
143
Langers lines
if you cut along the lines of a scar it will show less
elastic fibers of skin run in a certain way. if you cut the direction the elastic pulls, you wil get a smaller scar. if you cut so that the elastic fibers pull it open, you will get a bigger scar
144
Labile cell populations
bone marrow, gut epithelium, epidermis
| are always renewing themselve
145
stable cell populations
will renew themselves if some members die
| liver, other glands, fibroblasts
146
permanent cell populations
have very limited ability to replace lost members
| brain, heart
147
Wounds healing
1. fibrin
2. becomes granulation tissue
3. becomes scar
4. scar contracts
148
bread and butter pericarditis
fibrin on outer surface of the heart. looks like butter and ketchup
149
exuberant granulation tissue after injury
an exaggeration of normal healing, with granulation tissue rising above the surface, that may require surgical debridement
no on really understands why this sometimes hapens
150
New vessels sprout and grow
into fibrin, and wherever else they seem to be needed for healing.
most famous angiogenic factor is VEGF A. but even without, some vessels would surely sprout where needed
151
VEGF a
for vascular sprouting. cancer needs to trick blood vessels into going into tumor, does this through vegf-a
152
granulation tissue redness and softness
prominent vessels impart the redness
| edema the softness
153
developing granulation tissue has
nice new vessels, fibroblasts
| maturing vessels. plasma cells too
154
Collagen in trichrome stain
dense collagen is deep blue - lots of it in mature scar
155
wounds heal by ____ and ___ intention
primary
secondary
(old surgeons terms)
156
primary intention
edges are carefully approximated and everything goes perfectly --> tiny scar, everyone happy
well approximated, non infect, well nourished, no diabetes, not on glucocorticoids, clean, well vascularized area
157
secondary intention
messy cut, diabetic, etc --> healing by second intention, takes longer, not all that clen cut, bigger scar
158
adhesions
scar after surgery able to obstruct the bowel
gut is held tight by fibrous tissue, peritonitis, fibrous bands between loops of bowel that can cause obstruction down the road
159
myofibroblasts
fibroblasts with some contractile cytoskeleton. SCAR CONTRACTS at the end of the healing process
160
scar contraction can be detrimental if
it kinks the bowel (adhesion) or hinders joint movement
161
Keloid scar
a scar that's overly large, tends to expand over time, and has thick, glassy collagen fibers. serrations on edge of scar (crab claw). tend to keep expanding
162
hypertrophic scar
related to keloid. but lacks serrated edges. don't tend to keep expanding
163
result of longstanding ongoing epithelial damage
scar, according to big robbins.
increased damage of CT rather than epithelial tissue is what erf says causes ongoing scarring.
we see this in alcoholic liver cirrhosis and smokers lungs. cells maintain structure, but it's moot - if you're mangling an organ, you're mangling an organ
164
how does bone heal
fibroblasts to cartilage to new bone, like in kids
165
Inflammation 9 R's
```
Recognize the injury
Recruit white cells
Remove the threat
Regulate the immune response
Resolve the inflammation
Repair the damage
```
in Real life, most deaths Result from our final inflammatory Reaction
166
-tomy
cut something
167
-ectomy
cut something out
168
-ostomy
made a mouth to outside/between two organs
169
-plasty
reshaped
170
-pexy
moved something to the right place
171
-rraphy
sewed something up
172
-desis
made two things stick together
173
Aching pain
periosteum/tooth/dura/circuit in brain
174
burning pain
mucosal injury/nerve injury
175
crampy pain
hollow organ
176
stabbing pain
serosal membrane
177
ischemia, most everything else
something other than aching, burning, cramping, stabbing
