Powerpoint-Chap2 Flashcards
What are the acute inflammatory cell
granulocytes
What are the 3 main involvements of acute inflammation
vascular dilation and increased flow
microvasculature alterations to allow egress of cells and proteins
emigration, accumulation and activation of leukocytes
What are the 4 cardinal signs of inflammation
dolor-pain
calor-heat
rubor-redness
tumor-swelling
What is the 5th cardinal sign of acute inflammation
functio laesa-loss of function
What is the Lewis Triple response
red line(vasodilation)
red flare- after 15-30 seconds (vasodilation)
wheal in 1-3 minutes (vascular leakage)
what cells release histamine
mast cells
how can we completely stop inflammation
cutting the nerves involved
What can cause acute inflammation
infections, necrotic tissues, hypoxia, foreign bodies, immune reactions
what factor during hypoxia causes inflammation
hypoxic induced factor 1 alpha
what is released in necrotic tissue to cause inflammation
uric acid, ATP, HMGB-1 DNA
what are the main triggers of inflammation in an infection(foreign)
toll like R and cytoplasmic R
In a blood smear describe what neutrophils look like
have 3+ nuclei usually. young neutrophils have the banded nucleus
In a blood smear what do the eosinophils look like
hace 2 nuclei usually
In a blood smear what do the basophils look like
stain darker and very punctuated
What do the lymphocytes look like in blood smear? how do you tell them from monocytes
have oval purple nucleus
monocytes stain lighter, and have more cytoplasm(nucleus usually kidney shaped
What are majority of cells in a virus caused inflammation
lymphocytes
what are majority of cells in a pseudomonas caused reaction
neutrophil dominance
what is the normal pattern of cell population in acute inflammation
granulocytes early followed by monocytes
neutrophils followed by macrophages
What chemical mediators cause vascular permeability
histamine, bradykinin and leukotrienes
what is exudation and what causes it
fluid, proteins, RBC and WBC in intravascular space as a resuls of increased osmotic pressure extravascular, and increased hydrostatic pressure intravascular
What is vascular stasis
slowing of blood with vasodilation and fluid exudation to allow chemical mediators and inflammatory cells to collect and respond to stimulus
what 2 componenets contribute to vascular stasis
less blood (fluid loss) and vasodilation
what is the term margination
leukocytes accumulating on vascular endothelium
What are the two manifestations from vasodilation
erythema and warmth
what is histamines mechanism that leads to vascular permeability
causes endothelial cells to contract and so then there are gaps between cells
What are the other chemicals that increase vascular permeability
NO and VEGF
WBC have what barrier to escape through when endothelial cells contract and make pathways
basement membrane
have collagenase to chew through
what is transudate
ultrafiltrate of plasma leaking from vessls due to increase hydrostatic P or decrease P
what is exudate
mixture of cells and plasma leaking out of vessels in response to chemical mediators
What is purulent exudate
granulocyte rich, cellular debris, +/- microbes (pus)
Why is the nucleus on one side of the cell in a plasma cell
because rER is so large, squishes nucleus over to one side
what causes fibrinous pericarditis
exudate
What are the types of body cavity effusion
serous- yellow/clear serosanguinous- mixed sanguinous- blood purulent chylous
white and milky effusion is called what
chylous
which is more alkaline, transudate or exudate
transudate
if pressure increases in body, like increased Cardiac output, what leaks out
fluid- transudate
inflammation and increased P, what will leak out of cells
exudate- proteins, enzymes, maybe bacteria. Acidic. maybe odorous
what is dermatographism a reaction to
histamine. when we scratch ourselves and redness and wheal forms. this is when it lasts for more than 30 minutes
what is the immediate transient response
the leakage of histamines because vasodilation and endothelial cells contract. 15-30 minutes
No neutrophils!
What is the immediate sustained response
thermal chemical burns or lytic bacterial infection
leakage starts and lasts several hours to days
endothelial cell necrosis occurs
venules, capillaries and arterioles may be affected
What is delayed prolonged leakage
leakage 2-12 hours after injury
inflammation lasts hours to days
bacterial toxins, mild to moderate thermal burns
capillaries and venules affected- mechanism unclear
How does leakage drain
lymphatics
what is lymphangitis
inflammation of lymph vessels
what is lymphadenitis
inflammation of vessels and lymph nodes
what is adenitis
inflammation of lymph node
what are the steps in leukocyte emigration
stasis- margination- rolling- adhesion- migration
how do leukocytes migrate across the endothelium
chemotaxis towards concentration gradient
how do leukocytes migrate across basement membrane
chemotaxis, cytoskeleton, collagenases
how do leukocytes migrate into tissues
chemotaxis, integrins and CD44
what occurs first in leukocyte migration, crossing endothelium or basement membrane
crossing endothelium
TNF and IL1 increase expression of what on endothelium
P selectin, E selectin and integrin ligand (CAM1)
what cell has a weibel palade bodies
endothelial cells
Where is L selectin located
on the leukocyte
recurrent bacterial infections(not pustular), periodontitis and impaired wound healing are key to what pathology
rare, deficiencies in leukocyte adhesion molecules
What is CD99
normally repulses cells but changes to homophillic state and allows leukocytes to migrate through endothelial cells
When neutrophils bind and the GPCR is activated what occurs
increase Ca, kinases causing polymerization of actin (filopodia) can move towards signals
what are chemoattractants
cytokines, complement C5a, leukotriene B4
bacterial products
which complement component is chemotactic
C5a
what are the humoral endogenous chemotactic factors
fibrin split products (PMNs)
complement C5a and C567
What cells can be phagocytes
macrophages
neutrophils
what do phagocyte WBC recognize on targets
mannose R
scavenger R- LDL
opsonins
what does a classically activate macrophage do
kill bacteria
what do alternatively activated macrophages do
wound repair and anti-inflammatory
What are the antiinflammatory substances secreted from macrophages
IL10 and TGF beta
Chronic arthritis is due to what cells and molecules
lymphocytes macrophages and antibodies
chronic atherosclerosis is from what cells
macrophages and lymphocytes
what cells are responsible for chronic transplant rejection
lymphocytes and cytokines
what cells are responsible for pulmonary fibrosis
macrophages and fibroblasts
what cell is responsible for lug abscess
neutrophils
what chemicals are responsible for septic shock
cytokines
what cells and molecules are responsible for acute transplant rejection
lymphocytes, Ab and complement
what cells are responsible for acute respiratory distress sydnrome
neutrophils
What is chediak higashi syndrome
lysosome fusion disorder. phagolysosomes
what are problems with leukocytes with microbial activities. (deficiency)
decreased phagocyte oxidase leading to dec in ROS and results in chronic granulomatous disease and decreased MPO leading to recurrent candida infections
What type of diseases have impaired WBC production
bone marrow suppression, tumors, radiation and chemotherapy
what are our innate mechanisms to end acute response
mediators and neutrophils have short half lives
what are the active mechanisms in our bodies to end acute response
switch AA products
liberation of anti-inflammatory cytokines TGFb
prduction of anti-inflammatory lipid mediators (resolvins and protections)
neural changes (dec TNF by macrophages)
Describe how cell derived chemical mediators of inflammation are made
preformed or newly synthesized by simple splice to activate
what are the plasma derived mediators of inflammation
coagulation
complement and kinin
activation of normally present proteins by cascades
what cells make histamine
mast cells, basophils and platelets
what cell release serotonin
platelets and neuroendocrine cells
What cell releases NO
macrophages and the endothelium
What factor in coagulation cascade is key to set everything off
factor XII
what does serotonin do for inflammation
vasodilation, increased vascular permeability
What cells release TNF and IL 1
macrophages, endothelial cells and mast cells
where are complement and kinins produced
in the liver
what causes release of histamine
physical injury (triple response) neuropeptides (subP) Ab binding anaphylatoxins (C3a and C5a) leukocyte histamine releasing proteins cytokines (IL1 and IL8)
serotonin has similar activity to what other mediator
histamine
What R does histamine worked through
H1 R on endothelial cells
what are the primary roles of histamine
constrict large arteries
vasodilation
increase venular permeability via endothelial contraction
What inactivates histamine
histaminase
What sets off serotonin release
collagen, thrombin, ADP and Antigen Ab complexes
What are eicasanoids
AA metabolites
steroids inhibit what
phospholipases which make AA
Cox1 and 2 inhibitors block what
cyclooxygenase
Prostaglandin is converted into what
prostacyclin and thromboxane A2
what is the role of prostacyclin
vasodilation, inhibits platelet aggregation
what is the role of thromboxane A2
vasoconstriction, promotes platelet aggregation
What are derivatives produced via cycloocygenases
thromboxane A2
prostacycline
PGD2
PGE2 and PGF2
what is the effect of PGE2
pain and vasodilates
What does PGD2 cause
attracts neutrophils, vasodilates
pain and fever via cAMP action on temp set point
What do leukotrienes cause
bronchoconstriction, increase vascular permeability
cause vasoconstriction
attract leukocytes
what do lipoxins do
inhibit leukocyte recruitment and inflammation
Which leukotriene is responsible to attract leukocytes
B4
What do aspiring and other NSAIDs inhibit
Cox1 and 2
cox 1 makes what
thromboxane
cox 2 makes what
prostacyclines
cox 2 inhibitors impair what
endothelial cell production or prostacyclin (which is a vasodilator and inhibitor of platelet aggregation)
what is the problem with cox 2 inhibitors
increase risk of clot because cox1 unnopposed
lipoxogenase inhibitors are used for what
asthma
What cells make platelet activating factor
platelet, endothelial cells and leukocytes
what activates release of platelet activating factor
platelet aggregation, vasoconstriction, bronchoconstriction
enhanced leukocyte adhesion
at low concentrations causes vasodilation
What are the primary reactive species
O2-, H2O2, and OHelctron
when reactive species combine with NO what is product
ONOO electron
what causes ROS
endothelial cell damage
damage to parenchymal cells and erythrocytes
inactivate proteases
smoking kills what protein
alpha1 antitrypsin
What is the role of NO
relaxes smooth m
inhibits leukocyte rolling, adhesion and degranulation
inhibits platelet aggregation and adhesion
inhibits mast cell activated inflammation
What are the 3 types of nitrous oxide synthetase
constituitive: endothelial eNOS and Neuronal nNOS
inducible (iNOS) from monocytes and macrophages activated by TNF and INF gamma
what are cytokines
general category of messenger molecules
what are chemokines
special cytokines that direct leukocyte migration
How do chemokines work
bind to GPCRs
What activates TNF and IL 1
macrophages
What controls IL 1 production
inflammasome
what is the action of TNF and IL 1 generally
endothelial activation to activate adhesion molecules in the acute phase, fever and also activates fibroblasts and nuetrophils
Increased active IL 1 with mutation result in what
inherited autoinflammatory syndromes
Which cytokine is responsible for cachexia when sick( don’t want to eat)
TNF
what is happens to iron when we are sick
more hepcidin available which binds up all the iron. so looks like iron deficient(anemia) but not really
What are the azurophil granules
primary neutrophils that show up first
what are the specific granules(neutrophil)
secondary, show up second
What type of enzymes are in specific granules
more enzymes for digestion, like collagenase, lysozyme
What reaction is substance P known for
wheal formation
where are majority of neurons with substance P located
GI tract and lungs
what does sub P cause
pain, endocrine cells secretion, mast cell activation, vascular permeability
What is hageman factor XII involved in
activates clotting cascade, kinin cascade, fibrinolytic cascade, complement cascade
What do fibrin split products produce
chemostasis, inflammation
Which cascade results in production of bradykinin? what is bradykinins role
the kinin cascade from kallikrein make bradykinin
bradykinin activates C5 to C5a which causes more inflammation
plasmin has what affect on complement
splits C3 into C3a and b
Which Complement parts make MAC
C5b-Cp
What are the anaphylatoxins of complement cascade
C3a, C4a and C5a
what else does C5a do
leukocyte activation
chemotaxis
lipoxygenase increased activity
which complement parts are opsonins
C3b and iC3b
What do protease activated receptors cause
mobilization P selectin chemokine production Cox2 induction increased PGs PAF and NO endothelial adhesion endothelial conformation change
what are the actions of bradykinin
increased vascular permeability
smooth m contraction
pain
what is the role of kallikrein
positive feedback to XII, creates bradykinin
What is the role of plasmin in the fibrinolytic system of inflmmation
breaks down fibrin into split products
increase vasc permeability
chemotactic for leukocytes
what is the role of an anaphylatoxin
release histamine
What mediators play a role in vasodilation
PGs NO and histamine
what mediators increase vasc permeability
histamine, serotonin, C3a C5a bradykinin Leukotrienes
PAG and sub P
what mediators are included in chemotaxis
TNF IL 1 chemokines, C3a C5a leukotriene B4
What mediators induce fever
IL 1 TNF and PGs, PGE2!
what mediators induce pain
PGs and bradykinin!!!
what mediators induce tissue damage
lysosomal enzymes of leukocytes
ROS
NO
what is resolution
complete repair after inflammation
What is fibrosis from inflammation
collagen deposition and loss of function
if inflammation never goes away what is the problem
chronic inflammation
What is exudative acute inflammation
stuff coming out
what is serous inflammation
serous fluid coming out
what is fibrinoid vs fibrinous
fibrinous we can see it
fibrinoid is under microscope
urticarial inflammation means what
itchy
what is catarrhal inflammation
runny nose
What is cellulitis
inflammation of skin
what is necrotizing inflammation
necrotic inflammatory process
what type of inflammation is granulomatous
chronic
what is interstitial inflammation
in between layers
acute or chronic
what is cytopathic inflammation
cell has been modified- like in viruses
what is purulent vs serous
serous clear yellow
purulent- pus
pericarditis and endocarditis are examples of what inflammation
fibrinous
what does fibrinous inflammation look like under scope
very pink- lots of protein, lots of fibrin
what is pseudomembranous inflammation
form of exudative inflammation involving mucous and serous membranes
fibrin in exudate causes membrane like covering that is adherent to inflamed tissue
what types of infections cause pseudomembranous inflammation
c difficile colitis
corynebacterium diptheriae pharyngitis
what are mononuclear cell infiltrates in chronic inflammation
macrophages, lymphocytes, plasma cells, other cells
what does chronic inflammation arise from
continued infections
prolonged exposure to toxic/foreign agents
autoimmune diseases
malignancies
In acute viral infections what happens to neutrophil count
neutrophils go down. lymphocytes up
what are the characteristics of chronic inflammation
chronic inflammatory cells
destruction of parenchyma and replacement by CT
Describe life of monocytes
live in blood 1 day unless activated into macrophages which can live longer
What is the hallmark of chronic inflammation
tissue damage
What are the macrophages of body
alveolar macrophages in lungs microglia in CNS kupffer in liver osteoclasts in bone dendritic cells of many tissues langerhans are the dendritic cells of the skin
what are the 2 roles of macrophages
increase inflammation or begin repair
Why are benign cells found surrounding malignant cell
all the cehmoattractancts that the malignant cell is releasing
what is the perinuclear huff
the edge of the plasma cell that is dark around cytoplasm
what are produced in eosinophils
IL 3, IL 5
granulocyte/monocyte colony stim factor GM-CSF
what are the chemoattractans for eosinphils
LTB4, CCL5(RANTES) and eotaxin 1 and 2
what are in the granules in eosinophils
basic protein(toxic to parasites) cytotoxic agents like cationic proteins, neurotoxin and peroxidase
Which parasites that get attacked by eosinophils
helminths
what is the most common cause eosinophilia
allergies
How do you know if a cell is a basophil
cannot see the nucleus because it is so dark
what are the main components that are staining dark in basophils
histamine and heparin
big cell lots of cytoplasm
macrophages
what is the most common granulomatous disease
TB
If the nuclei of a giant cell are around the edge what are they called
langhans type giant cell
Describe histo sarcoidosis
granulomas
no central necrosis like we see in TB
mainly macrophages
describe difference of cat scratch fever compared to other granulomas
has neutrophils in the areas as well
What cytokines are responsible for fever in inflammation
IL1 IL 6 TNF and IFN gamma
What cytokines are generated in large amounts that causes sepsis
TNF IL1
what is neutropneia or agranulocytosis
too few circulating neutrophils
What can cause neutrophil adherence molecule problems
hereditary, DM, glucocorticoid admin, ehtanol
what chronic disease can cause failure of neutrophils to move properly
DM
what can cause failure of neutrophils to phagocytose
DM, complement of Ig deficiencies
Insufficient Oxygen radicals can lead to what type diseases
chronic granulomatous diseases
Major burns can cause what deficiency
chemotaxis
what can lead to deficiencies in phagocytosis and microbial activity
leukemia, anemia, sepsis, DM, neonates and malnutrition
