What are the Cardinal Signs of Inflammation?
Loss of Function (Functio laesa)
What is the triple response?
Redness due to arteriolar and capillary vasodilation
Flare; redness in the surrounding area, due to diffusion of histamine and early stasis
Wheal: due to exudation of fluid from the post capillary venules
What physiological change is responsible for both heat and redness of acute inflammation?
Vasodilation (usually we are talking about arterial)
What rarely can occcur before vasodilation?
Rarely, there may be an initial transient vasoconstriction
What chemical cause vasodilation?
Histamine and NO acting on vascular smooth muscle
What is stasis?
The term to desribe vascular congestion of packed red cells moving slowly in dilated small vessels. Stasis leads to neutophils accumulating along the vascular endothelium
-blood vessels dilate to slow down blood blow and by increasing their permeability
What are the two possible sources of acute inflammation due to vascular response?
Microbes and Necrotic Tissue
How llng will inflammation exist?
Until the inciting stimulkus is removed and the mediators are dissipated or inhibited
Edema is the result of what physiological mechanism
Vasodilation that leads to increased vascular permeability and the leakage of fluid out of the blood vessels.
Compare exudate to transudate
Exudate is fluid and protein leakage that contain WBCs and cellular debris, and has a high specific gravity (Pus)
-Transudate is a fluid with low protein content, it is essentially an ultra-filtrate of blood plasma that results from osmotic or hydrostatic imbalance across the vesssel wall wihtout an increase is vascular permeability. Can be caused by venous outflow obstruction like congestive heart failure.
What are some pathogenesis of non-inflammatory edema?
Pulmonary edema due to Heart Failure
Nephortic syndrome due to renal distrubance (low albumin)
What are some pathogenesis of inflammatory edema?
Direct, irreversible injury - all vessels (burns)
or transient increases in vascular permeabiltiy like the triple response
What are the sequential step in leukocyte extravasation?
Margination, rolling, and adhesion (pavementing), transmigration or extravasation
-on histo slide margination is the dark stained spots moving out toward the cytosplasm and pavmenting is when they actually begin to stick, the proper adhesion molecules must be present.
Why is it important to determine exudate vs. transudate and what is the example?
Transudate you treat with directics, and exudate you treat with antibiotics. example is an exray that shows effsion in the pleural space and infiltrate in teh long. is it pneumonia or heart failure. you have to tap teh effusion with a needle and test the cell count, specific gravity, and protein level. then determine and treat
Give examples of both exogenous and endogenous chemo-attractants that result in chemotaxis?
Exogenous: N-formyl methionine terminal amino acids from bacteria, LPS
Endogenous: complement proteins (C5a) chemokines (IL-8), Arachidonic acid products (LTB4)
-chemotaxis is the leukocyte migrating toward the site of injury after extravasation, movement is by extension of filopodia
The inflammasome is responsible for the celavage and activation of which chemokine?
What is transcytosis and what are molecules involved in performing it?
Contraction of endothelial cells resulting in increased inter-endothelial spaces is the most common mechanism of vascular leakage. Usually occurs in post-capillary venules (hallmark of acute inflammation)
-NO, Histamine are important
What are the important molecules that mediate the adhesion of leukocytes to the endothelium?
L-selectin is expressed on leukocytes
P-selectin is expressed on platelets
E-selectin is on endothelial cells
the expression of selectins is regulated by cytokines in response to injury including TNF and IL-1
What are some mediators of P-selectin and when does it occur?
Thrombin, Platelete-activating factor, and histamine stimulate the redsitribution of p-selectin from the weibel-palade bodies to the cell surface.
What molecules induce E-selectin?
TNF-alpha and IL-1
When Leukocytes are activated, what is their primary mechanism for killing the microbes that ingest through phagocytosis?
ROS within the lysosome
Along with ROS, leukocytes also have granulocytes that contain many enzymes to aid in the killing of microbes. What are some of these enzymes?
Elastase and Lysoszyme, defensins, cathelicidns, lactoferrin
What enzyme makes eosinophils particularly effect against parasites?
Major basic protein, which is toxic to many parasites. they may also contain histaminase
What are two important molecules in the termination of inflammation?
TGF-beta (transforming growth factor) - anti-inflammatory cytokine from macrophages
What is the enzyme that makes Arachidonic acid?
Phospholipase A2 turns cell membrane phospholipids into arachidonic acid
What inhibits phospholipases?
What must occur for healing to occur?
What are the two ways an organ can heal?
Regeneration (liver) or collagenous scarring (result of ECM damage),
-regeneration is optimal!
What is fibrosis?
A type of repair that results in a collagen scar. Functional tissue replaced by collagenous scar, which is laid down by fibroblasts
What are some influences a growth factor can have on healing?
Rate of healing, type of ECM depositied, and cell types present