inflammation Flashcards
inflammation
immunologic defence against tissue injury, infection or allergy
function of inflammatory response
restitution of normal, functioning cell after injury
fibrous repair when restitution of functioning cells is impossible
injuries that cause inflammation
mechanical, thermal, electrical, chemical, radiation, biological assault
steps of inflammatory response (8)
TVSIMEMR
- tissue injury - release of chemical mediators
- vasodilation + increase blood flow
- swelling + retraction of endothelial cells
- increased vascular permeability + leakage of small plasma proteins
- movement of immune response cells to injury site
- exudate formation
- movement of glucose + oxygen to injury site
- release of chemical repair factors from endothelial cells
populations at greatest risk
very young
very old
uninsured
exposure to secondhand smoke
smoke irritates eyes and mucous membranes of respiratory tract. irritation causes inflammation
excessive exposure to sun
results in sun burn (thermal injury)
exposure to infection
infection always accompanied by inflammation
rheumatoid arthritis
inflammation of joints and surrounding tissues
first line of defence is?
innate immunity (natural) physical, mechanical, biochemical barriers
second line of defence is?
inflammatory response
third line of defence is?
adaptive immunity (acquired)
physical barriers
describe
line of defence
1st line of defence - skin - lining of gastrointestinal, genitourinary, respiratory tract > sloughing of cells > coughing and sneezing > flushing - urine > vomiting > mucous and cilia
epithelial cell-derived chemical barriers
describe
line of defence
1st line of defence
- secrete saliva, tears, earwax, sweat and mucous
- antimicrobial peptides
- normal microbiome
inflammatory response
describe
line of defence
nonspecific
regulated by chemical mediators
what materials cause inflammatory response
infection, tissue necrosis, ischemia, trauma, physical/chemical injury, foreign bodies, immune reaction
local manifestations of inflammatory response
redness, heat, swelling, pain, loss of function
inflammatory response
vascular
vasodilation
increased vascular permeability and leakage
WBC adherance to inner wall of vessels
goals of inflammation
prevent/limit infection or further damage
limit/control immune response
initiate adaptive immune response
initiate healing
list three protein systems
complement
clotting
kinin
complement system
produces biologically active fragments that recruit phagocytes, activate mast cells and destroy pathogens
activation of C3 and C5
most important to complement system
opsonins
chemotactic factors
anaphylatoxins
pathways of complement system
CAL
classical: antigen-antibody reaction
alternative: bacterial endotoxin
lectin: independent of antibody
clotting system
forms blood clots at an injured/inflamed site
what do blood clots do
prevents spread of infection
localizes micro organisms and foreign bodies
stops bleeding
framework for repair/healing
main substance in clotting system
insoluble protein - fibrin
pathways of clotting system
extrinsic: activated by tissue factor
intrinsic: factor XII
kinin system
activate and assist inflammatory cells
primary kinin
bradykinin
what does the kinin system do
cause dilation o blood vessels and smooth muscle contraction, induces pain, increase vascular permeability
cellular components of inflammation
EPL
erythrocytes
platelets
leukocytes
types of leukocytes
granulocytes
monocytes
lymphocytes
cellular receptors of inflammation
bind a large spectrum of antigens
different receptors recognize specific molecules
types of receptors
PPDTCSN
- Pattern recognition receptors (PRRs)
- Pathogen-associated molecular patterns (PAMPs)
- Damage-associated molecular patterns (DAMPs)
- Toll-like receptors (TLRs)
- Complement receptors
- Scavenger receptors
- NOD-like receptors (NLRs)
what are cytokines responsible for
activating other cells and regulating inflammatory response
cytokines can be either
pro-inflammatory (induce)
anti-inflammatory (inhibit)
types of cytokines
CITI
chemokines
interleukins
tumor necrosis factor-alpha
interferon
chemokines synthesized by
pro or anti
different cells in response to pro-inflammatory cytokines
chemokines induce
chemotaxis to promote phagocytes and wound healing
examples of chemokines
- monocyte/macrophage chemotactic proteins
- macrophage
inflammatory response - neutrophils
interleukins produced by
macrophages and lymphocytes in response to stimulationof PRRs or other cytokines
many types
examples of interleukins
IL-1 proinflammatory
IL-10 anti-inflammatory
tumour necrosis factor-alfa secreted by
macrophages in response to PAMP and toll-like receptor recognition
tumour necrosis factor-alfa induces
fever
acts as endogenous pyrogen
tumour necrosis factor-alfa increases
synthesis of inflammatory serum proteins
tumour necrosis factor-alfa causes
muscle wasting and intravascular thrombosis
high levels of tumour necrosis factor-alfa can be
lethal
interferons protect against
viral infections
interferons produced and released by
virally infected host cells in response to viral DS RNA
types of interferons
IFN-a and INF-b:
induce production of antiviral proteins
IFN-y:
increase microbiocidal activity of macrophages
mast cells
cellular bags of granules located in the
loose connective tissues close to blood vessels
mast cells contain
histamine, cytokines, and chemotaxic factors
mast cells release
degranulation
synthesis
mast cell degranulation
release of the contents of mast cell granules
mast cells synthesis
new production and release of mediators in response to stimulus
mast cell degranulation
histamine
-vasoactive amine
causes temporary, rapid constriction of large blood vessels and dilation of postcapillary venules
- retraction of endothelial cells lining the capillaries causing increased vascular permeability
mast cell degranulation
receptors
H1 and H2
H1 receptor
pro-inflammatory
present in smooth muscle cells of the bronchi
H2 receptor
anti-inflammatory
present on parietal cells of the stomach mucosa
induces the secretion of gastric acid
leukotrienes
product of arachidonic acid from mast cell membranes
similar effects to histamine in later stages
prostaglandins
similar to leukotrienes (induce pain)
aspirin and some NSAIDS block synthesis of prostaglandins
platelet-activating factor
similar to leukotrienes and platelet activation
types of phagocytes
neutrophil eosinophil basophil monoctye/macrophage dendritic
neutrophils
- polymorphonuclear neutrophils (PMNs)
- predominate in early inflammation
- ingest bacteria, dead cells and cellular debris
eosinophils
- mildly phagocytic
- defence against parasites and regulation of vascular mediators
basophils
- least prevalent granulocytes
- primary role unknown
monocytes and macrophages
monocytes in bone marrow>circulation>migrate to inflammatory site>become macrophages
arrive 24 hours after neutrophils
dendritic cells
peripheral organs and skin
migrate through lymph to interact with T lymphocytes to generate acquired immune response
phagocytosis
process by which cells ingest and dispose of foreign material
margination
adherence of leukocytes to endothelial cells in the walls of capillaries
diapedesis
emigration of cells through the endothelial junctions
5 steps of phagocytosis
- adherence
- engulfment
- phagosome
- fusion with lysosomal granules
- destruction of target
natural killer cells
recognize and eliminate cells infected with viruses
local manifestations results of acute inflammation
vascular changes and corresponding leakage of circulating components into the tissue
examples of local manifestations of acute inflammation
heat, swelling, redness, pain, loss of function
exudative fluids
serous exudate
watery exudate
indicates early inflammation
ex - blister fluid
fibrinous exudate
thick, clotted exudate
indicates more advanced inflammation
ex - pneumonia
purulent exudate
pus
indicates bacterial infection
ex - cyst or abscess
hemorrhagic exudate
contains blood
indicates bleeding
systematic manifestations
fever
leukocytes
increased plasma protein synthesis
fever caused by
exogenous and endogenous pyrogens
act directly on hypothalamus
leukocytes
increased number of circulating leukocytes (WBC)
increased plasma protein synthesis
acute phase reactants
examples of acute-phase reactants
- C-reactive protein
- fibrinogen
- haptoglobin
- amyloid
- ceruloplasmin
what is chronic inflammation characterized by
pus formation, supperation
incomplete wound healing
other causes of chronic inflammation
- high lipid and wax content of a micro organism
- ability to survive inside macrophage
- toxins
- chemicals, particulate matter or physical irritants
characteristics of chronic inflammation
- dense infiltration of lymphocytes and macrophages
- granuloma formation
- epithelioid cell formation
- giant cell formation
hypersensitivity def.
altered immunological response to an antigen that results in disease or damage to the host
allergy
hypersensitivity
deleterious effect of hypersensitivity to environmental antigens
autoimmunity
disturbance in immunological tolerance of self-antigens
4 types of immune mechanisms
type I IgE mediated
type II tissue specific
type III immune complex-mediated
type IV cell-mediated
type I
against environmental antigens
histamine release from mast cell degranulation
type I
IgE binds to
Fc receptors on surface of mast cells
type I manifestations
GI allergy
nausea, vomiting, diarrhea, abdominal pain
type I manifestations
skin
urticaria (hives)
type I manifestations
mucosa allergens
conjunctivitis, rhinitis,
asthma
type I manifestations
lung allergens
bronchospasm, edema, thick secretions
type II
specific cell or tissue is the target of an immune response
type II
five mechanisms
- cell destroyed by antibodies and complement
- cell destruction through phagocytosis
- soluble antigen enter circulation and deposit on tissues
- antibody-dependent cell -mediated cytotoxicity
- target cell malfunction
type III mediated by
immune complex
type III antigen-antibody
complexes formed in circulation
later deposited in vessel walls or extravascular tissues
type IV mediated by
cell-mediated hypersensitivity
what do type IV not invlove
antibodies
strain
stretching injury
strain involves
muscle/tendons
strain caused by
mechanical overload
sprain involves
ligaments
incomplete or completely torn
pain and swelling resolve faster in in sprain or strain
strain
sprain caused by
irregular or excessive movement of a joint
symptoms of sprain
pain rapid swelling heat disability discolouration limited function
sprain strain treatment
anti-inflammatory analgesics
gradual return to activity
RICE
rest
ice
compression
elevate
osteoarthritis characterized by
- loss+damage of articular cartilage
- inflammation
- new bone formation in joint
- subchondral bone chanes
- variable degrees of mild synovitis
- thickening of joint capsule
prevalence of ____ increased with age
osteoarthritis
risk factors of osteoarthritis
- increased age
- joint trauma
- long-term mechanical stress
- obesity
manifestations of osteoarthritis
pain stiffness enlargement of joint tenderness limited motion muscle wasting partial dislocation deformity
conservative treatment of osteoarthritis
exercise and weight loss
drugs (analgesics and anti-inflammatory)
nutritional supplements
surgical treatment of osteoarthritis
used to improve joint movement, correct deformity or malalignment, or create new joint with artificial implants
prostaglandins
lipids that promote inflammation and are found in all tissues
cyclooxygenase
key enzymes in the biosynthesis of prostaglandins
two forms of cyclooxygenase
cyclooxygenase-1
cyclooxygenase-2
cyclooxygenase-1
location
all tissues
cyclooxygenase-1
function
protects against gastric mucosa, support kidney function, promote platelet aggregation
cyclooxygenase-1
inhibited by medications
undesirable:increase risk for gastric bleeding and kidney failure
cyclooxygenase-2
location
all sites of injury
cyclooxygenase-2
function
mediates inflammation, sensitizes pain receptors, mediates fever in brain
cyclooxygenase-2
inhibited by medications
desirable: results in suppression of inflammation
NSAIDs
nonsteroidal anti-inflammatory drugs
NSAIDs action
inhibit cyclooxygenase->blocking inflammation
NSAIDs drug of choice for
mild to moderate pain, inflammation, fever
properties of all NSAIDs
antipyretic
analgesic
anti-inflammatory
use of NSAIDs
relief of: mild/moderate headache myalgia neuralgia arthralgia post-op pain arthritis pain treatment of gout and hyperuricemia
celecoxib (celebrex®)
NSAID cyclooxygenase inhibitor
adverse effects of NSAIDS
heartburn to severe GI bleeding acute kidney injury noncardiogenic pulmonary edema altered hemostasis hepatotoxicity skin eruption tinnitus
tinnitus
hearing loss
misoprostal
prevents GI bleed
synthetic prostaglandin E1 analogue that inhibits gastric acid secretion
NSAIDs nursing considerations
take with food/milk avoid alcohol assess for GI bleed monitor I&O no children
glucocorticoids action
suppresses histamine release and inhibits syntheses of prostaglandins by inhibiting COX-2
glucocorticoids released by
adrenal cortex
natural hormone
glucocorticoids helps control inflammatory response by
stabilizing cell membranes of inflam cells (lysosomes). decreases migration if WBC into already inflamed areas
prednisone
Apo-Prednisone
glucocorticoids prototype
glucocorticoids routes
inhaled or injected
glucocorticoids inhaled
control of steroid-responsive bronchospastic states
glucocorticoids nasal admin
manage allergic rhinitis and prevent recurrence of polyps after surgical removal
glucocorticoids topical
used in management of inflammation of eye ear skin
methylprednisolone sodium succinate
most common injectable glucocorticoid
hydrocortisone sodium succinate and dexamethasone sodium succinate
second most common injectable glucocorticoids
glucocorticoids - prednisone
action
potent anti-inflam: short acting systemic corticosteroid
glucocorticoids - prednisone
contraindications
active untreated infections, lactation, hypersensitivity to alcohol, bisulfate or tartrazine (food additive)
glucocorticoids - prednisone
dosage
5-60 mg/day
week to a month
glucocorticoids - prednisone
adverse effects
depression, euphoria, headache, personality change, psychosis, restlessness, increased intraocular pressure, increased BP, peptic ulcers, anorexia, nausea, vomiting, delayed wound healing, increased blood glucose, decreased potassium, weight gain, osteoporosis, moon face
acetaminophen
Tylenol
pain reliever
max dose 4g/24 hrs
opioid analgesic
Ultram (tramadol)
- extended release
- synthetic - similar to morphine
- considered weak
- binds to receptors in brain responsible for transmitting pain signals and inactivates them
- manage moderate to severe pain
Ultracet or Tramacet
contains acetaminophen
viscosupplementation
- injected like cortisone
- available OTC oral supplement
- ex synvisc, orthovisc
eczema
“atopic dermatitis”
- inflam condition
- chronic (relapse and exacerbation)
- non contagious
- genetic predisposition
- eviron trigger
- immune dysregulation
- disturbance to epidermis
- stress
eczema manifestations
dry skin itching erythema papules infiltration
eczema therapy
symptomatic emollients oil bath topical moisturizer anti-inflam UV therapy topical antifungal systemic antibiotics severe: systemic immunosuppressives (cyclosporine)
anaphylaxis
most severe hypersensitivity
occurs within minutes of exposure
systemic or cutaneous
desensitization
reduce the severity of allergic reaction
can cause anaphylaxis
antihistamines
drugs that directly compete with histamines for receptor sites
properties of antihistamines
antihistaminic
anticholinergic
sedative
histamine antagonists
H1 and H2
H1 antagonist examples
ex: chloropheniramine, fexofenadine (Allegra®), loratadine (Claritin®), cetirizine
(Reactine®), desloratadine (Aerius®),
diphenhydramine (Benadryl®)
H2 antagonist examples
cimetidine, ranitidine (Zantac®),
famotidine (Pepcid AC®), nizatidine (Axid®)
H2 antagonists used to
reduce gastric acid in peptic ulcer disease
Diphenhydramine hydrochloride
traditional antihistamine (Benadryl) acts both peripherally and centrally
Diphenhydramine hydrochloride also has
anticholinergic and sedative effects
anaphylaxis pharmacotherapy
symptomatic
support cardiovascular system and prevent further hyper-response
what does an epipen do
rapidly reverse hypotension
what is in an epipen
epinephrine
andrenergics
common diagnostic tests
lab
CBC WBC with differential CRP ESR serological test to detect specific antibodies or viruses
common diagnostic test
radiographic
MRI
CAT
PET scan
colonoscopy
CBC
complete blood count
WBC
white blood cell
CRP
C-reactive protein
ESR
erythrocyte sedimentation rate
MRI
magnetic resonance imaging
CAT
Computerized Axial Tomography
PET
positron emission tomography
pregnancy risk category for medications
A
adequate
well controlled studies
not shown risks to fetus
pregnancy risk category for medications
B
no adequate well controlled studies in women
studies in animals not found risks to fetus
pregnancy risk category for medications
C
no adequate well controlled studies in women
animal studies found harmful effect on fetus
or not studied in women or animals
caution advised, benefits may outweigh risks
no adequate well controlled studies
D
clear risk to human fetus
benefits may outweigh risks for pregnant women with serious condition
no adequate well controlled studies
X
clear evidence that medication causes abnormalities in fetus
