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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
Q

mechanism of ectopic discharges in neuropathic pain

A

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

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26
Q

treatment options for peripheral neuropathic pain

A

reduce excitability of neurons
carbamazepine
gabapentin

27
Q

what are some inflammatory states that can cause an acute phase response

A 
infection
trauma
infarction
inflammatory arthritides
autoimmune/inflamm diseases
neoplasms
28
Q

what are acute phase reactants

A

proteins who’s serum concentrations increase or decrease by at least 25% during inflammatory states
may be positive or negative

29
Q

what is ESR measuring

A

indirect APR

reflects plasma viscosity and the presence of acute phase proteins, especially fibrinogen

30
Q

what do changes in APR levels reflect

A

altered production by hepatocytes

effects of cytokines like IL-6, IL-1B, TNFa, and IFNy

31
Q

albumin as an APR

A

negative APR

synthesis is repressed with inflammation

32
Q

positive APRs

A 
fibrinogen
a1 antitrypsin
haptoglobin
IL-1 receptor antagonist
hepcidin
ferritin
procalcitonin
33
Q

negative APRs

A

albumin
transferrin
transthyretin
(large proteins)

34
Q

neuroendocrine effects of the acute phase response

A 
increased production of corticotropin release hormone
muscle wasting
cachexia
impaired growth in children
secondary amyloidosis
35
Q

changes induced by acute phase response

A

fever
anemia
anorexia, somnolence, lethargy

36
Q

what is CRP

A

c reactive protein
both proinflammatory and anti inflammatory actions
produced in liver
primarily anti inflammatory effects

37
Q

describe the CRP

A

5 identical non-covalently associated subunits around a central pore

38
Q

major function of CRP

A

bind phosphocholine

recognition of foreign pathogens that display this moiety and phospholipids constituents of damaged cells

39
Q

proinflamm effects of CRP

A

activate complement
induction in monocytes of inflamm cytokines and TF
shedding of IL-6 receptor

40
Q

serum amyloid A (SAA)

A

major acute phase protein family
apolipoproteins associated with HDL
influence cholesterol metabolism during inflammatory states

41
Q

haptoglobin and hemopexin

A

antioxidants that protect against ROS

remove iron containing cell-free hemoglobin and heme from circulation

42
Q

a1 antitrypsin

A

inhibits superoxide anion generation

43
Q

a1 antichymotrypsin

A

antagonize proteolytic enzyme activity

44
Q

hepcidin

A

produced in liver
contribute to decreases in serum iron by reducing intestinal iron absorption and impairing release of iron from macrophages

45
Q

fibrinogen

A

endothelial cell adhesion, spreading, and proliferation

critical to tissue repair

46
Q

haptoglobin

A

stimulates angiogenesis

granulation tissue components

47
Q

what do abnormalities in APR reflect

A

presence of an inflammatory process

48
Q

marked ESR elevation

A

more often due to infection than other causes

49
Q

conditions than can raise ESR in the absence of inflammation

A 
increased age and female sex
anemia
renal disease
obesity (IL-6 secretion)
technical factors (lab errors)
50
Q

why might ESR be very low when it is expected to be high due to inflammation

A 
erythrocyte abnormalities
extreme leukocytosis
high serum bile salts
heart failure
hypofibrinogenemia
cachexia
technical factors (lab error)
51
Q

what do you do if ESR is much lower than expected?

A

repeat test

52
Q

what is a “normal” CRP

A

70-90% of populations have CRP < 0.3

some have minor elevations up to 1

53
Q

CRP > 1

A

clinically significant inflammation

54
Q

CRP 0.3-1

A

low grade inflammation

55
Q

CRP > 10

A

highly indicative of bacterial infection

56
Q

elevated ESR with normal CRP

A

misleading

example: monoclonal immunoglobulins

57
Q

acute phase reactants in SLE

A

ESR elevated
CRP response is muted
comparison of ESR and CRP is useful when infection is suspected

58
Q

why is CRP muted in SLE

A

type 1 interferons highly expressed in lupus patients and inhibit CRP induction in hepatocytes

59
Q

when will CRP be high in lupus

A

active lupus serositis
chronic synovitis
bacterial infection when >6-7

60
Q

acute phase reactants in RA

A

ESR and CRP generally tend to both be elevated or not in same patient
monitor disease activity

61
Q

acute phase reactants in PMR and GCA

A

correlate well w disease activity and are useful in diagnosis

62
Q

acute phase reactants in cardiovascular disease

A

predictive value of CRP in CVD

63
Q

acute phase reactants in infection

A

assess response of infections to treatment

64
Q

acute phase reactants in malignancy

A

assess prognosis in some
clonal vs reactive process
tumor presence or absence

MM Test 1 (20 decks)

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