Unit 3 - Acute Inflammation Flashcards
The response of living tissue to injury. Involves a well-organized cascade of fluidic and cellular changes:
Inflammation
What is the primarily delivery system for inflammatory components?
blood
mediated by prostaglandins that are increased in the hypothalamus
fever
Which prostaglandins produce fevers?
TNF, IL-1, IL-6
What increases cyclooxygenases that convert AA to prostaglandins (PGE2)
Cytokines
How do NSAIDs reduce fever?
by inhibiting prostaglandin synthesis
Stimultes acute phase protein production by the liver:
IL-1, IL-6
List the three common acute phase proteins:
- C-reactive protein
- SAA
- Fibrinogen
Predominance of mononuclear cells is characteristic of:
chronic inflammation
What are the primary mononuclear cells?
macrophages, lymphocytes, plasma cells
The inner wall of an abscess is granulation tissue, called a:
pyogenic membrane
Standardized reaction, Early response; Hours to days:
acute
Alteration of an inflammatory; weeks to years:
chronic
What are the goals of acute inflammation?
- dilute toxins
- isolate
- eliminate
- repair
Increased _______ often indicates a bacterial infection:
neutrophils
Increased ______ are associated with viral infections:
lymphocytes
an abnormally high number of circulating white blood cells:
leukocytosis
What part of the brain coordinates a fever?
hypothalamus
5 Cardinal Signs of Inflammation:
Heat, redness, swelling, pain, loss of function
What is the stimulus that triggers inflammation?
tissue injury
List three exogenous stimulants of inflammation:
microbes, foreign bodies, and injury (chemical, thermal, heat, ischemia)
List the 2 endogenous inflammation stimulants:
hypersensitivity, autoreactive
Inflammation activates the:
innate immune response
What is the cellular phase of acute inflammation?
leukocyte emigration
What is the fluidic phase of acute inflammation?
microvascular exudation of electrolutes, fluid, and plasma proteins
How does the body recognize invaders/foreign material?
- cellular receptors
- cellular sensors
- circulating proteins
Where are some of the cellular receptors located on immune cells?
- PM (extracellular)
- cytosol (intracellular)
- endosome (ingested)
Each TLR recognizes:
a different set of microbial molecules
TLR-4 recognizes:
LPS
PAMPs associated with:
microbial structures
DAMPs associated with:
released from necrotic cells
Which cytosolic receptors recognize a diverse set of molecules and active the inflammasome?
- bacterial products
- crystals
- K+ efflux
- reactive O2 species
Inflammasomes induce the production of:
IL-1
IL-1 recruits:
leukocytes
Receptors located on the plasma membrane that detect fungal glycans and elicit inflammation to fungi:
C-type lectin receptors
receptors that recognize antibodies and complement proteins:
Fc (recognize opsonized material)
circulating proteins that react against microbes and produces mediators of inflammation:
complement
substances that initiate and regulate inflammatory reactions:
mediators of inflammation
What are some ways inflammatory mediators are kept in check?
- short half-lives
- enzymatically destroyed
- scavenged by antioxidants
One mediator can stimulate the release of:
other mediators
What organ constantly secretes inflammatory mediators from plasma proteins?
liver
What cell types produce histamine?
mast cells, basophils, and platelets
What is the function of histamine?
vasodilation
increased vascular permeability
What cell types produce serotonin?
mast cells, platelets
What is the function of serotonin?
similar to histamine
List the synthesized mediators (3):
- cytokines
- chemokines
- arachidonic acid metabolites
Which cells are the primary activators of cytokines?
macrophages, lymphocytes, dendritic cells
Which cytokines are responsible for acute inflammation?
TNF, IL-1, IL-6
What is the function of cytokines?
regulate immune and inflammatory reactions
4 main functions of cytokines?
- endothelial activation
- leukocyte recruitment
- leukocyte activation
- systemic acute phase response
cytokines that promote leukocyte chemotaxis and migration:
chemokines
secreted by activated macrophages, endothelial cells, and others
IL-8
Which interleukin causes the chemotaxis of neutrophils?
IL-8
What are the lipid mediators produced from arachidonic acid present in membrane phospholipids?
prostaglandins, leukotrienes
Prostaglandin function:
vasodilation
leukotriene function:
vasoconstriction, increased vascular permeability, chemotaxis/leukocyte adhesion
Thromboxane function:
vasoconstriction
Collection of soluble proteins and membrane receptors that function in host defense; circulate as inactive form in plasma
complement system
deposition of the MAC results in:
cell lysis
Which complement cleavage products stimulate inflammation via histamine release?
C3a and C5a
Which complement cleavage product is chemotactic for leukocytes?
C5a
Which complement cleavage product is useful for opsonization/phagocytosis?
C3b
Activates the intrinsic coagulation AND catalyzes the formation of kallikrein:
factor 12
Functions of bradykinin:
- increased vasc. permeability
- vasodilation
- pain
What is the function of kallikrein?
plasminogen –> plasmin
cleaves C3
Synthesized by endothelial cells and macrophages:
nitric oxide
3 functions of nitric oxide:
- vasodilation
- inhibits platelet aggregation and adhesion
- oxidizes lipids
Platelet activating factor functions in:
vasoconstriction and bronchoconstriction
Which principal mediators are responsible for vasodilation?
histamine
prostaglandins
Which principal mediators are responsible for increased vascular permeability?
- histamine
- serotonin
- C3a, C5a
- leukotrienes
Which principal mediators are responsible for chemotaxis, leukocyte recruitment, and activation?
- TNF
- IL-1
- IL-8 (neutrophil chemotaxis)
- Chemokines
- C3a, C5a
- Leukotrines
Which principal mediators are responsible for fever?
- IL-1
- TNF
- Prostaglandins
Which principal mediators are responsible for pain?
- prostaglandins
- bradykinins
Which principal mediators are responsible for tissue damage?
- lysosomal enzymes of leukocytes
- reactive oxygen species
Which phase of acute inflammation functions in dilution and localization of the stimulus?
fluidic phase
Sequence of vascular events of the fluidic phase:
- increased blood flow
2. increased permeability of capillaries and postcapillary venules
Why does increased vascular permeability mainly occur in venules?
high density of histamine receptors
What allows for the retraction of endothelial cells?
actin/myosin
results from increased vascular permeability
serous fluid
suggests that the injury is rather mild or peracute
serous fluid
clear watery fluid with low concentration of plasma protein and no/low # of leukocytes
serous fluid
What are some likely times you will see serous fluid?
mild skin injury, allergy (runny nose), serosal surfaces
What does the histology of serous fluid typically look like?
affected tissues are spread apart by watery fluid
Dehydration of serous exudate released from injured vessels:
serous crust
termed used to describe a PATTERN of acute inflmmation:
fibrinous inflmmation
Exudate that has leakage of large molecular weight proteins (fibrinogen) that then polymerize to form fibrin:
fibrinous inflammation
Accumulation of fluid with a high concentration of plasma protein:
exudate
Where is fibrinous exudate most commonly seen?
in serous membranes of body cavity (pleura, pericardium, peritoneum, synovial membrane)
What is the gross appearance of fibrinous exudate?
- surface tissue is often hyperemic
- early - surface may be granular and dull
- surface covered with fibrin
Fibrinous exudate on histopath often involves:
- eosinophilic proteinaceous material - often fibrillary
- rapidly infiltrated by neutrophils
If extensive, fibroblasts may migrate in and begin organizing exudate leading to fibrinous adhesions:
fibrinous inflammation
Delivers leukocutes to the site in order to kill and/or digest the stimulus (neutrophils and macrophages)
cellular phase
What are the steps of the cellular phase (4)?
- Margination
- Rolling
- Adhesion to endothelium
- Migration
Which cytokines enhance expression of rolling and adhesion?
TNF, IL-1
Exongenous products that induce chemotaxis:
- bacterial products
- some lipids
Endogenous products:
- IL-8
- complement
- arachidonic acid
Monocytes/macrophages are seen how many hours after injury?
24-48
Neutrophils are seen how many hours after injury?
6-24
The first cells to arrive depends on the:
stimulus
Neutrophils are the first cells to arrive in a:
bacterial infection
Lymphocytes and plasma cells are the first to arrive in:
hypersensitivity reactions
Eosinophils are the first to arrive in:
allergic reactions
Lymphocytes are the first to arrive in:
viral infections
Which type of inflammation involves a response consisting of an accumulation of fluid with high concentrations of plasma proteins and high number of neutrophils?
purulent inflammation
Which term is often used synonymously with purulent but often implies that a larger amount of pus is present?
suppurative
an accumulation of dead neutrophils
pus
If the purulent exudate is white, it means:
neutrophils are predominant component
If the purulent exudate is yellow:
there is lots of necrotic debris
What are the three types of consistencies associated with purulent inflammation?
- watery
- creamy
- firm
When purulent inflammation is mixed with fibrin:
fibrinopurulent
on microscopic examination, you will see large numbers of neutrophils, many degenerate neutrophils and mixed with necrotic cellular debris, tissue debris, plasma proteins, and fibrin:
purulent inflammation
If purulent inflammation progresses to chronic inflammation it becomes:
an abscess
Mediated by prostaglandins that are increased in the hypothalamus:
fever
Which cytokines mediate fever?
TNF, IL-1, IL-6
Increase production of leukocytes by the bone marrow:
TNF, IL-1, IL-6
stimulate acute phase protein production by the liver:
IL-1, IL-6
What are the acute phase proteins? (3)
- c-reactive protein
- SAA
- fibrinogen
Cytokines and acute phase proteins affect (3):
heart rate, blood pressure, body temp
clinically significant form of bacteremia complicated by toxemia, fever, malaise, and often shock:
septicemia
Septicemia gross findings:
fluid in body cavity, pulmonary edema, petechial hemorrhages, congestion of the liver and intestine
Septicemia histologic findings:
acute necrosis of renal tubules, centrolobular hepatocytes, and cardiac myocytes
What is the major interleukin that recruits neutrophils?
IL-8
How long do neutrophils live in the tissue?
1-2 days
How long do neutrophils live in circulation?
24 hours
List the 2 main functions of neutrophils:
- phagocytosis
- release of granular contents
What’s different about cow neutrophils?
cytoplasm is more eosinophilic
What are two other names for neutrophils?
myeloid cells
PMNs
What are the important granules released by neutrophils?
- myeloperoxidase
- lysozyme
converts hydrogen peroxide (and chloride anions) to hypochlorous acid (toxic to microbes)
myeloperoxidase
form pores in membranes
defensins
enzymes released by neutrophils cause liquefaction of the exudate and:
accumulation of pus
Reptiles and birds have reduced concentration of the enzymes released by neutrophils and thus:
cannot liquefy the exudate (and a caseous material forms)
extracellular fibrillary networks that provide a high concentration of antimicrobial substances
NETs
What are NETs composed of?
meshwork of nuclear chromatin
How long do eosinophils live in circulation?
12 hours
How long do eosinophils live in the tissue?
1 week
What are eosinophils attracted by?
histamine, eosinophil chemoattractant factor A
When do eosinophils enter lesions?
during the transition from acute to chronic
Gives the muscle a tan-green tinge:
large numbers of eosinophils in the CT of muscles
Found in all supporting tissues:
mast cells/basophils
How long do mast cells live?
4-12 weeks
Have the ability to replicate in tissues:
mast cells
Which type of cell is distributed in skin, GI, and around blood vessels?
mast cells
Mast cells express high affinity for which immunoglobulin?
IgE
Which stain type is used to see the metachromatic granules of mast cells?
Giemsa
In circulation, monocytes are:
short lived
In tissues, macrophages are _____-____ are retained the ability to proliferate:
long-lived
What are the three functions of monocytes/macrophages?
- phagocytosis
- antigen presentation
- immune modulation
Macrophages of the liver:
Kupffer cells
Macrophages of the CNS:
microglia
Macrophages of the lungs:
alveolar macrophages
Macrophages of the skin:
Langerhans cells
Macrophages of the bone:
osteoclasts
Which cell type arrives as a second wave after neutrophils - 12-48 hours - and takes over?
macrophages
What do platelets arise from?
megakaryocyte fragmentation in marrow
Which preformed substance do platelets carry?
histamine
Offending agent is quickly eliminated, little tissue is damaged:
complete resolution
agent persists, particularly one that is strongly chemotactic for neutrophils:
abscess
With substantial parenchymal injury and loss, granulation tissue fills in the defects:
healing by fibrosis
- hyperemia is typical, often with protein rich fluid exudate
- neutrophils are the predominant leukocyte
acute
- characterized by fibrous and vascular proliferation
- reduced hyperemia
- parenchymal proliferation
- few to no neutrophils
chronic
What are some chronic modifiers?
- granulomatous (lots of macrophages)
- lymphocytic
- lymphoplasmocytic
- fibrosing
- proliferative
What are some causes of serous inflammation?
- early reaction to many inciting causes
- trauma to joints
- burns
What is the function of a serous exudate?
dilution of offending agent
Exudate of accumulation of serum-like fluid
serous inflammation
Secretion of large amounts of mucus that occurs only in mucous membranes:
catarrhal inflammation
What can cause catarrhal inflammation?
- mild irritants
- mild/early inflammation
What is the gross appearance of catarrhal inflammation?
clear film
What is the microscopic appearance of catarrhal inflammation?
- pale blue strands of mucus
- may be mixed with inflammatory cells
Exudate containing a large amount of fibrin:
fibrinous exudate
What is the gross appearance of fibrinous exudate?
dull granular to thick sheets
What is the microscopic appearance of fibrinous exudate?
fibrillar eosinophilic material
Exudate containing large numbers of neutrophils, necroptic tissue cells, fibrin, and necrotic inflammatory cells:
suppurative/purulent exudates
collection of pus with a fibrous capsule:
abscess
Which type of exudate reflects severe vascular injury, arises quickly, and is often fatal?
hemorrhagic exudate
Hemorrhagic exudate often involves:
mucosal surfaces
Hemorrhagic exudate gross appearance:
deep red and pink to red-tinged fluid is present
Which type of exudate can accompany many disease processes?
hemorrhagic
suggests severe destruction of host tissue (recruits inflammation, calls in fibrins):
necrotizing
a covering of a mucosal surface by a coagulum of fibrin, mucus, necrotic cells, and leukocytes:
pseudomembranes
How can you tell if a pseudomembrane is present?
when the exudate is peeled away, leaves an ulcerated mucosal surfacce
Inflammation of the kidney due to a bacterial infection:
pyelonephritis
An infection in any part of the urinary system, the kidneys, bladder, or urethra:
cystitis
What is the pathogenesis for the lay-down of fibrin on an organ?
acute inflammation, leakage of protein –> deposition of fibrin
If you see whispy material on histo, what most likely are you seeing?
fibrin
