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MM Test 1 > B6.011 Prework: Pain & Acute Phase Reactants > Flashcards

B6.011 Prework: Pain & Acute Phase Reactants Flashcards

1
Q

what is pain

A

subjective
unpleasant sensory/emotional experience
evokes by actual or potentially noxious stimuli

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2
Q

parts of the nociceptive system

A

free nerve endings in peripheral tissue
afferent nerve fibers
synapses in dorsal horn of spinal cord
ascending tracts into brain

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3
Q

function of acute physiological nociceptive pain

A

protective and prevents further damage

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4
Q

hyperalgesia

A

increased sensitivity to pain

can be thermal or mechanical

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5
Q

allodynia

A

pain elicited by stimuli that are normally below the pain threshold

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6
Q

neuropathic pain

A

injury or disease of nociceptive neurons in the peripheral or central nervous system

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7
Q

causes of neuropathic pain

A

nerve or plexus damage
DM
herpes zoster

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8
Q

nociception

A

encoding and processing of noxious stimuli in the nervous system
can be measured objectively: normal relationship between nociception and pain is precise and predictable

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9
Q

chronic pain

A

pain longer than 6 months

less strict relationship between nociception and pain

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10
Q

what types of neurons are responsible for peripheral nociception

A

sensory neurons with thinly myelinated Ad or unmyelinated C fibers

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11
Q

describe the components involved in peripheral nociception

A

sensory neurons
cell bodies located in dorsal root ganglia
terminate in dorsal horn of the spinal cord or in the brain stem
activate synaptically nociceptive dorsal horn neurons

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12
Q

dual function of sensory neurons involved in nociception

A 
sensory function (encodes noxious stimuli)
transport neuropeptides (substance P and CGRP)
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13
Q

discuss the transportation of neuropeptides in sensory neurons

A

cell body to the periphery
release in the tissue on stimulation
induce vasodilation, plasma extravasation, attraction of macrophages, and/or degranulation of mast cells
contribute significantly to many inflammatory disease

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14
Q

what does polymodal mean?

A

nociceptors respond to mechanical, thermal, and chemical stimuli

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15
Q

what structures in the joints are innervated with nociceptors

A 
fibrous capsule
ligaments
adipose tissue
menisci
synovial layer
NOT cartilage
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16
Q

how are nociceptors in joints activated

A 
strong pressure
noxious movements (painful rotation)
NOT by movements and positions in the working range
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17
Q

muscle nociceptors location and activation

A

location: muscle belly, tendon
activation: painful compression, ischemic contraction

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18
Q

cutaneous nociceptors activation

A

respond to noxious heat and mechanical stimuli like squeezing

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19
Q

what are silent nociceptors

A

relatively mechanoinsensitive
heat insensitive
recruited during inflammation (sensitized)

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20
Q

how are silent nociceptors sensitized

A

repetitive or strong noxious stimulation of the tissue
heavy inflammation
decreased excitation threshold of polymodal nociceptors

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21
Q

impact of peripheral sensitization

A

enhanced input to spinal cord

induces central sensitization

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22
Q

what happens once silent nociceptors are sensitized

A

become excitable by both innocuous and noxious stimuli

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23
Q

describe peripheral sensitization

A

major pathophysiological mechanism of primary inflammatory joint diseases like RA, OS, and myositis
movements in working range and palpation of joints are painful
pain in absence of stimuli

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24
Q

etiology of neuropathic pain

A

damaged nerve fibers show pathologic ectopic discharges
action potentials generated at the site of nerve injury
cell bodies of impaired fibers located in dorsal root ganglia

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25
mechanism of ectopic discharges in neuropathic pain
expression of Na+ channels alters the membrane properties of the neuron such that rapid firing rates are favored injured axons directly excited by inflammatory mediators affected by sympathetic nervous system
26
treatment options for peripheral neuropathic pain
reduce excitability of neurons carbamazepine gabapentin
27
what are some inflammatory states that can cause an acute phase response
``` infection trauma infarction inflammatory arthritides autoimmune/inflamm diseases neoplasms ```
28
what are acute phase reactants
proteins who's serum concentrations increase or decrease by at least 25% during inflammatory states may be positive or negative
29
what is ESR measuring
indirect APR | reflects plasma viscosity and the presence of acute phase proteins, especially fibrinogen
30
what do changes in APR levels reflect
altered production by hepatocytes | effects of cytokines like IL-6, IL-1B, TNFa, and IFNy
31
albumin as an APR
negative APR | synthesis is repressed with inflammation
32
positive APRs
``` fibrinogen a1 antitrypsin haptoglobin IL-1 receptor antagonist hepcidin ferritin procalcitonin ```
33
negative APRs
albumin transferrin transthyretin (large proteins)
34
neuroendocrine effects of the acute phase response
``` increased production of corticotropin release hormone muscle wasting cachexia impaired growth in children secondary amyloidosis ```
35
changes induced by acute phase response
fever anemia anorexia, somnolence, lethargy
36
what is CRP
c reactive protein both proinflammatory and anti inflammatory actions produced in liver primarily anti inflammatory effects
37
describe the CRP
5 identical non-covalently associated subunits around a central pore
38
major function of CRP
bind phosphocholine | recognition of foreign pathogens that display this moiety and phospholipids constituents of damaged cells
39
proinflamm effects of CRP
activate complement induction in monocytes of inflamm cytokines and TF shedding of IL-6 receptor
40
serum amyloid A (SAA)
major acute phase protein family apolipoproteins associated with HDL influence cholesterol metabolism during inflammatory states
41
haptoglobin and hemopexin
antioxidants that protect against ROS | remove iron containing cell-free hemoglobin and heme from circulation
42
a1 antitrypsin
inhibits superoxide anion generation
43
a1 antichymotrypsin
antagonize proteolytic enzyme activity
44
hepcidin
produced in liver contribute to decreases in serum iron by reducing intestinal iron absorption and impairing release of iron from macrophages
45
fibrinogen
endothelial cell adhesion, spreading, and proliferation | critical to tissue repair
46
haptoglobin
stimulates angiogenesis | granulation tissue components
47
what do abnormalities in APR reflect
presence of an inflammatory process
48
marked ESR elevation
more often due to infection than other causes
49
conditions than can raise ESR in the absence of inflammation
``` increased age and female sex anemia renal disease obesity (IL-6 secretion) technical factors (lab errors) ```
50
why might ESR be very low when it is expected to be high due to inflammation
``` erythrocyte abnormalities extreme leukocytosis high serum bile salts heart failure hypofibrinogenemia cachexia technical factors (lab error) ```
51
what do you do if ESR is much lower than expected?
repeat test
52
what is a "normal" CRP
70-90% of populations have CRP < 0.3 | some have minor elevations up to 1
53
CRP > 1
clinically significant inflammation
54
CRP 0.3-1
low grade inflammation
55
CRP > 10
highly indicative of bacterial infection
56
elevated ESR with normal CRP
misleading | example: monoclonal immunoglobulins
57
acute phase reactants in SLE
ESR elevated CRP response is muted comparison of ESR and CRP is useful when infection is suspected
58
why is CRP muted in SLE
type 1 interferons highly expressed in lupus patients and inhibit CRP induction in hepatocytes
59
when will CRP be high in lupus
active lupus serositis chronic synovitis bacterial infection when >6-7
60
acute phase reactants in RA
ESR and CRP generally tend to both be elevated or not in same patient monitor disease activity
61
acute phase reactants in PMR and GCA
correlate well w disease activity and are useful in diagnosis
62
acute phase reactants in cardiovascular disease
predictive value of CRP in CVD
63
acute phase reactants in infection
assess response of infections to treatment
64
acute phase reactants in malignancy
assess prognosis in some clonal vs reactive process tumor presence or absence

MM Test 1 (20 decks)

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