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
What is the first structural glycoprotein laid down during wound healing?
What allows integrins to be able to influence diapedesis?
The direct connection to actin
What are the steps in wound healing?
1. Induction of acute inflammatory response
2. regeneration of parenchymal cells
3. synthesis of extracellular matrix proteins
4. migration and proliferation of both parenchymal and connective tissue cells
6. collagenization and maturation of wound
What is granulation tissue?
initial event in the repair of injury, and consists of richly vascular connective tissue which contians capillaries, young fibroblasts, and a variable infiltrate of inflammatory cells
-do not confuse this with granulomatous inflammation (a form of chronic inflammation)
Describe primary intention wound healing?
Clean wound with well-apposed edges and minimal clot formation
Describe the wound and its cellular composition at these time intervals: Less than 24 hours, day 3, day 5, 2nd week, and end of 1st month.
Healing by Primary Intention:
• Within 24 hours, neutrophils appear at the margins of the incision, moving toward the fibrin clot. In 24 to 48 hours, spurs of epithelial cells move from the wound edges (with little cell proliferation) along the cut margins of the dermis, depositing basement membrane components as they move. They fuse in the midline beneath the surface scab, producing a continuous but thin epithelial layer that closes the wound.
• By day 3, the neutrophils have been largely replaced by macrophages. Granulation tissue progressively invades the incision space. Collagen fibers are now present in the margins of the incision, but at first these are vertically oriented and do not bridge the incision. Epithelial cell proliferation thickens the epidermal layer.
• By day 5, the incisional space is filled with granulation tissue. Neovascularization is maximal. Collagen fibrils become more abundant and begin to bridge the incision. The epidermis recovers its normal thickness, and differentiation of surface cells yields a mature epidermal architecture with surface keratinization.
• During the second week, there is continued accumulation of collagen and proliferation of fibroblasts. The leukocytic infiltrate, edema, and increased vascularity have largely disappeared. At this time, the long process of blanching begins, accomplished by the increased accumulation of collagen within the incisional scar, accompanied by regression of vascular channels.
• By the end of the first month, the scar is made up of a cellular connective tissue (“cellular cicatrix”) devoid of inflammatory infiltrate, covered now by intact epidermis. The dermal appendages that have been destroyed in the line of the incision are permanently lost. Tensile strength of the wound increases thereafter, but it may take months for the wounded area to obtain its maximal strength.
Describe healing by secondary intention?
Wound edges are not apposed (wound infection). Wound fills with granulation tissue from the bottom up. results in a large scar
What is wound contration?
occurs in secondary intention usually of large surface wonds. involves the reduction in size of teh defect by the action of myofibroblasts which represent an intermediate type of cell. Process produces faster healing, since a smaller portion must be repaired. But too much contration can create clinical problems.
What is the most common cuase of wound dehiscence or ulceration? What are some other potential causes?
Wound infection, hpoxia, malnutirtion (scurvy)
What are some clinical examples of contracttion?
Compartment syndromes (circumferential burns), Dupuytren contracture, peyronie's disease
What is dehiscence vs. ulceration
Dehiscence is rupture of a wound usually like an abdominal surgery wound that ruptures due to pressure or vomiting.coughing.
Ulceration is due to inadequat vascularaization during healing.
What is responsible for directing the cellular ballet of wound healing?
What is contracture?
Excessive contration of a wound. probelm with extensive circumferential like third degree burns