Inflammation 1 Flashcards
what is inflammation
an integrated and tightly controlled set of events associated with the body’s response to:
- injury
- infection
- insult
- itself
injury
trauma
tissue damage/necrosis
infection
bacterial
fungal
virus
insult
chemical radiation thermal foreign body environmental substances
itself
autoimmunity to self antigens
cardinal signs of inflammation
external manifestations of vascular change and leukocyte recruitment/activation
examples of the cardinal signs of inflammation
- Calor (heat)
- Rubor (redness)
- Tumor (swelling)
- Dolor (pain)
- Functio laesa (loss of function)
what are the 5 R’s of inflammatory response
- Recognition of injurious agent
- Recruitment of leukocytes
- Removal of agent
- Regulation (control) of response
- Resolution (repair) of damaged tissue
what happens if injury persists
chronic inflammation
what is acute inflammation
immediate response (minutes to days)
what is the specificity of acute inflammation
limited specificity
characteristics of acute inflammation
- neutrophils
* fluid and plasma exudation
chronic inflammation
delayed response (days to years)
specificity of chronic inflammation
more specificity
characteristics of chronic inflammation
- lymphocytes & plasma cells
- vascular proliferation and scarring
vascular changes of acute inflammation
- vasodilation
- increased vascular permeability
cellular events of acute inflammation
- neutrophil emigration
- cellular recruitment
- activation of neutrophils
what is vasodilation
locally increased blood flow due to arteriolar smooth muscle relaxation
vasodilation is mediated by what
prostaglandins
histamine
bradykinin
characteristics of vasodilation
- erythema (rumor)
- warmth (calor)
what occurs with increased vascular permeability
- movement of protein-rich fluid into extra-vascular space
- endothelial contraction (histamine)
- endothelial disruption (tissue damage)
- swelling (tumor)
what is effusion
-greater than normal volume of fluid within the pericardial, abdominal or pulmonary cavity
classifications of effusion
- transudate
- exudate
found in pleural or peritoneal cavity
how do differentiate between transudate and exudate
-based primarily on the protein [ ]
transudates
fluids of non-inflammatory origin with low protein concentration
transudates caused by increased volume caused by alterations in hydrostatic factors as:
- increased venous pressure (heart failure, hepatic cirrhosis with portal hypertension)
- hypoproteinemia (nephrotic syndrome, protein losing enteropathy)
- lymphatic blockage
exudates characterized by
- increased protein concentration
- frequently contain inflammatory cells (turbid0
- glucose concentration decreased
exudates caused by
- malignancy
- infection
- pancreatitis
where can effusion be collected from
-chest or abdomen - semi surgical procedures
what is thoracentesis
- collection of effusion through chest wall
- plural fluid
what is paracentesis
- through abdominal wall
- ascitic fluid
what is pericardiocentesis
- collection of effusion from pericardium
- pericardial fluid
- not a bedside procedure
what are the mediators of acute inflammatory response
- neutrophils
- endothelial cells
- mast cells
- eosinophils
- platelets
- toll like receptors
- arachidonic acid metabolies
- complement
- Hageman factor (Factor XII)
where do mature neutrophils emerge from
bone marrow
neutrophils are controlled by
chemokines (can circulate in blood for 6-8 h in blood)
what are other clinical names of neutrophils
- polymorphonuclear cells
- PMNS
- polys
- segs
neutrophils are central to acute or chronic inflammation
acute
action of neutrophils
phagocytose microorganisms and tissue debris
appearance of neutrophils
cytoplasm with granules (primary, secondary, tertiary)
what do neutrophils express
-selectins and integrins for binding to other cells and to migrate out into interstitum
neutrophils express receptors which recognize
- Fc porton of IgG and IgM
- C5a, C3b and iC3b (complement)
- cytokines
how are neutrophil extracellular traps formed
when neutrophils undergo oxidative burst and degranulation
what are endothelial cells
monolayer of cells lining blood vessels
function of endothelial cells
- regulates vascular contraction and relaxation
- regulates platelet aggregation
do nonactivated platelets bind normal endothelium
no
what can endothelial cells express
unregulated levels of adhesion molecules (ICAM and VCAM) which can anchor activated neutrophils
where are mast cells located
adjacent to vessels and widely distributed throughout connective tissue (ie. lug, GI mucosal surfaces, skin)
what do mast cells contain
preformed histamine granules (aretriolar vasodilation and increased vascular permeability of postcapillary venues)
mast cells are activated by
-trauma
-cross-linking of cell-surface IgE receptors
C3a and C5a complement proteins
what is the immediate response of mast cells
release of preformed histamine granules
what is the delayed response of mast cells
- arachidonic acid metabolites (leukotrienes)
- second phase of mast cell acute inflammatory response)
soon after the release of mast cells it is inactivated by
histaminase
eosinophils are associated with what type of reaction
- allergic rxn
- parasite associated rxn
- acute and chronic inflammatory rxns
eosinophils release
-cytoplasmic granules with lysosomal enzymes, cytokines and major basic protein (toxic to parasites)
platelets are formed from
megakaryocytes in bone marrow
appearance of platelets
bits of cytoplasm (no nucleus)
platelets contain
inflammatory mediators as dense granules and alpha granules
function of platelets
promote clot formation
toll-like receptors are present on what type of cells
- innate immune system (macrophages, dendritic cells)
- epithelial cells
- lymphocytes
function of toll-like receptors
recognize molecular structures common to microbes
TLR activation leads to upregulation of
cytokines
arachidonic acid is released from
phospholipid cell membrane by phopholipases
what are arachidonic acid metabolites called
eicosanoids
arachidonic acid derived from
20 carbon F/As
what are the 2 main pathways of arachidonic acid
- cyclooxygenase produces prostaglandins
- 5-lipoxygenase produces leukotrienes
what factors ofthe cyclooxygenase pathway cause vasodilation and increased vascular permeability
PGI2
PGD2
PGE2
what mediates pain in the cyclooxygenase pathway
PGE2
what causes vasoconstriction and platelet aggregation in the cyclooxygenase pathway
TXA2
what causes neutrophil chemotaxis and activation in the 5-lipoxygenase
LTB4
what causes smooth muscle contraction (vasoconstriction, brochospasm, increased vascular permeability)
LTC4
LTD4
LTE4
what causes neutrophil inhibition in 5-lipoxygenase
LXA4
LXB4
what is complement
serum proteins which “complement”/help host defense and inflammation
complement proteins C1 to C9 circulate as
inactive precursors
what is the critical step of complement
formation of C3 convertase which cleaves and activates C3
C3 cleavage occurs in what 3 pathways
- alternative pathway
- classical pathway
- lectin pathway
classical pathway
C1 complement component binds IgG or IgM bound to antigen
alternative pathway
microbial cell wall components (ie. endotoxin) directly activates complement
lectin pathway
plasma lectin binds to mannose residues on microbes (direct pathway)
what are the complement disorders
- hereditary angioedema
- paroxysmal nocturnal hemoglobinuria (PNH)
- Factor H deficiency
what is Hereditary angioedema
-deficiency of C1 inhibitor
function of C1 inhibitor
regulator of various components of clotting, complement and clotting cascade
consequences of hereditary angioedema
- increased vascular permeability under skin
- submucosal and subcutaneous swelling
- laryngeal edema can lead to death
what is paroxysmal nocturnal hemoglobinuria (PNH)
-deficiency of decay activating factor (DAF)
function of DAF (decay activating factor)
normally limits C3 and C5 formation
PNH results in
complement-mediated lysis of RBCs (Hemolytic anemia)
function of factor H
normally limits convertase formation
Factor H deficiency results in
- higher than normal C3b deposition on endothelium
- hemolytic uremia syndrome (HUS)
- spontaneous vascular permeability in macular degeneration of eye
what is the product of the kinin system
bradykinin
what are the direct effects of bradykinin
- increased vascular permeability (very potent)
- arteriolar dilatation
- pain
bradykinin is inactivated by
kininases in plasma and tissue
