1.2.1 Acute Inflammation and Wound Healing Flashcards
What are the cardinal signs of inflammation?
Redness (rubor), swelling (tumor), heat (calor), pain (dolor), loss of function (functio laesa)
Identify some of the variety of stimuli of acute inflammation.
Infections, tissue necrosis, foreign bodies (splinters, dirt, sutures), and immune reaction (hypersensitivity)
What physiological change is responsible for both heat and redness of acute inflammation?
Blood vessel dilation
Sir Thomas Lewis identified the triple response of inflammation and immunity, what are three components?
Redness, Flare, Wheal
What causes the redness?
arteriolar and capillary vasodilation (rarely, there may be initial transient vasoconstriction)
What does flare refer to?
Redness in the surrounding area, due to diffusion of histamine and early stasis
What is the cause of wheal?
Exudation of fluid from post-capillary venules; outpouring of protein-rich fluid into the extravascular tissues
What are the two possible sources of acute inflammation due to vascular response?
Microbes and Necrotic tissue
How long will inflammation persist?
Until the inciting stimulus is removed and the mediators are dissipated or inhibited
Within the vascular response of acute inflammation, what is the purpose of monocytes and granulocytes after they exit the vasculature?
Elimination of microbe or dead tissue
Edema is a result of physiological mechanism?
Vasodilation, which leads to increased vascular permeability
What are some characteristics of exudate?
Extravascular fluid w/ high protein content, and may contain some WBC and red cells, high specific gravity (ex. Pus)
What are some characteristics of transudate?
Low protein content, little to no cellular content (occurs as a result of decreased colloid osmotic pressure)
What are some pathogenecities of non-inflammatory edema?
Pulmonary edema due to HF
Nephrotic syndrome due to renal disturbance (low albumin)
What are some pathogenecities of inflammatory edema?
Direct, irreversible injury - all vessels (burns)
Transient increases in vascular permeability (triple response)
Give examples of both exogenous and endogenous chemo-attractants that result in chemotaxis?
Exogenous: N-formyl Met terminal AA from bacteria, LPS
Endogenous: Complement proteins (C5a), Chemokines (IL-8), Acrachidonic acid prod (LTB4)
The inflammasome is responsible for the cleavage and activation of which chemokine?
IL-1
What are some of the omnipresent proteins in plasma that can recognize microbes and damaged cells?
Complement proteins, mannose-binding lection, and collectins
What are some of the molecules involved in the retraction of endothelial cells?
Histamine, NO, other mediators
What are the sequential steps in leukocyte extravasation?
Margination, rolling, pavementing (adhesion), transmigration or extravasation
What are some of the signaling molecules that induce expression of P-selectins on the surface of leukocytes?
Thrombin, histamine, and PAF (platelet activating factor)
What molecules induce E-selectin on endothelium?
TNF-alpha and IL-1
When leukocytes are activated, what is their primary mechanism for killing the microbes that ingest through phagocytosis?
ROS
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 lysozyme, defensins, cathelicidins, lactoferrin
What enzyme makes eosinophils particularly effective against parasites?
Major basic protein. Also, contain histaminase.
What are two important molecules in the termination of inflammation?
TGF-beta (transforming growth factor) - anti-flammatory cytokine from macrophages
Neural impulses (cholinergic discharge) that inhibits TNF prod from macrophages
IL-10
Where do cortiosteriods work in the arachidonic acid pathway?
They inhibit phospholipase A2 (the very first step)
What process is occurring b/t these two images? What type of cell is responsible for the increased # of nuclei?
Leukocyte-mediated tissue injury; Neutrophils
What must occur for healing to occur?
Inflammation
What are the two way in which an organ can heal?
Regeneration (liver) or collagenous scarring (result of ECM damage)
What is the optimal type of repair?
Regeneration; liver is the best example of regeneration repair in humans
What is fibrosis?
A type of repair that result in a collagen scar. Functional tissue replaced by collagenous scar, which is laid down by fibroblasts
What are some of the influences a specific growth factor can have on wound healing?
Rate of healing, type of ECM deposited, and cell types present
What is the first structural glycoprotein laid down during wound healing?
Fibronectin
What causes integrins to be able influence diapedesis?
Their direct connection to the actin cytoskeleton
What the steps in wound healing?
- induction of an acute inflam. response
- regeneration of parenchymal cells
- synthesis of ECM proteins
- Migration and proliferation of parenchymal and connective tissue cells
- Remodeling
- Collagenizaiton and maturation of wound
What is the difference b/t granulation tissue and granulomatous inflammation?
Granulation tissue is the initial event in the repair of an injury, and consists of richly vascular connective tissue.
Granulomatous inflammation is a form of chronic inflammation
What are some characteristics of wound that will heal by primary intention?
Clean wound with well-apposed edges and minimal clot formation
Describe the wound and its cellular composition at these time intervals: Less than 24 hrs, day 3, day 5, during 2nd wk, and by the 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 (i.e. wound infection). Wound fills with granulation tissue from the bottom up. Large scar
What is the most common cause of wound dehiscence or ulceration? What are some other potential causes?
Wound infection; hypoxia or malnutrition (scurvy)
What is contracture?
excessive contraction of a wound
Give some clinical examples of contracture?
Circumferential contracture of 3rd degree burns
Dupuytran’s of the palm
Peyronie’s of the dick
What is responsible for directing the cellular ballet of wound healing?
ECM
What is exudate caused by?
Formed in inflammation because vascular permeability increases as a result of increased inter-endothelial spaces
What is transudate caused by?
Formed when fluids leak out because of increased hydrostatic pressure or decreased osmotic pressure. No change in the permeability of the vessel.
Usually a case with a surgical wound in which there is a clean wound, with well-apposed edges and minimal clot formation is an example of what type of healing?
Primary healing
When wound edges cannot be opposed, then the wound slowly fills with granulation tissue from the bottom up, resulting in a large scar is an example of what healing
Secondary intention healing
What is the role of contraction in second intention healing?
Myofibroblasts promote faster healing by reducing the size of the defect by contraction.
What is dehiscence?
Wound dehiscence is a surgical complication in which a wound ruptures along the surgical incision, tends to be caused by infection or malnutrition
Excessive contraction in second intention healing can lead to what?
Exaggeration is referred to as a contracture, and it can lead to compartment syndrome.
What is the role steroids can have in healing?
Steroids will reduce inflammation which will halt the healing process
