1c continued Flashcards
Chemical mediators general overview a 4 groups according to function
All S&S of inflammation are produced by chemical mediators
1 vasoactive properties
2 activate complement (clotting and kinin)
3 Chemotactic factors
4 Direct affectation of tissue cells
Histamine
Found preformed in mast, basophils and platelets.
Released from trauma or immune reactions (IgE binding)
First on scene
Binds to H1 (antihistamines often competitively antagonize H1)
Causes dilation of arterioles, and increases permeability of venules.
Considered principle mediator of immediate transient phase of increased vascular permability
Histamine H1 receptors specifically
-Promote inflammation from vasodilation, increased vascular permeability (due to retraction of endothelial cells lining caps)
-Chemotaxis
-Prostaglandin synthesis
Smooth muscle effects are bronchoconstriction and vasodilation
Histamine H2 receptors functions
Negative feedback (decrease histamine release) which reduces activity of lymphocytes and eosinophils, decreases neutrophil chemotaxis, decrease granulation of mast cells
H2 location
Parietal cells of stomach mucosa which increase gastric secrtion
Arachidonic acid two pathways
It is found in phospholipid bilayers and released by phospolipase A2. Release leads to Cyclooxygenase pathway (prostaglandins and thromboxane) Lipoxygenase pathway (leukotrienes)
Leukotrienes effects and pathway
Similar to histamine
Constricts pulmonary airway
Increase microvascular permability
From AA to lipoxygenase to leukotriens)
Prostaglandins
Promotes and inhibits inflammation cell response
Induces vasodilation
Induces vasoconstriction
From AA to cyclooxygenase
Thromboxane
From AA to cylcooxygenase pathway
Promotes platelet aggregation, vasodilation, bronchoconstriction
Arachadonic acid metabolites
Lipoxygenase (leukotriene receptor antagonist) Leukotrienes
Cyclooxygenase (asprin NSAID) prostaglandin and thrombaxane
Platelet Activating Factor
Lipid stored in membranes, induces platelet aggregation, activates neutrophils, chemotactic factor eosinophils
Plasma Proteins Three interrelated systems
Clotting, complement, and kinin
Inactive and need to be triggered
Clotting Cascade plasma proteins
Produces chemokines, expression of endothelial adhesion molecules, prostaglandin synthesis
Thrombin binds to PARs which triggers production of these plus PAF
Complement system plasma proteins
Contribute by causing vasodilation, increasing vasc permeability, enhancing phagocyte activity, and forms Membrane Attack Complex MAC
Kinin System plasma proteins
Release of bradykinin:
Increased vasc perm
Smooth muscle contraction
Vasodilation and incites pain when bound to nociceptors
Cytokines
Proteins produced by many different cells which cause functional effects on other cell types
Examples tumor necrosis factor-a and interleukin-1
They are released by macrophages and cause a wide range of effects
There are several forms of interleukins
Chemokines
Chemotactic cytokines
They are proteins that attract leukocytes and other inflammatory cells to site of injury
Nitric oxide
Smooth muscle relaxation, platelet antagonism, reduction of leukocyte recruitment
Can be considered a mechanism that prevents cell stage of inflammation from going too far
Produced by many cells
ROS
Produced during phagocytosis, released exogenously Exogenous effects of ROS: Increased vasc perm Increased endothelial adhesion Increasion expression of cytokines
Exudates
Serious - watery fluids low in protein, a result of large amounts of plasma
Hemorrhagic - caused by vessel damage, or increased leaking of RBCs into tissue
Fibrinous - large amounts of fibrinogen (similar to a clot)
Membranous - develop on mucous membranes
Purulent - contains pus (degraded WBCs, proteins, tissue debris)
Abscess
Localized inflammation with purulent (pus) exudate
Has a central necrotic core surrounded by a layer of neutrophils
POSSIBLY surronded by a layer of fibroblasts which would prevent anti-microbial agents from entering
This is why you often see abscess’ drained
Ulceration
Localized inflammation with epithelial damage
Erosion of tissue
From trauma or vasc deficits
Chronic inflammation
2 weeks + Not self-limiting, self-perpetuating caused by: recurrent acute inflammation progressive acute persisten low grade irritants
Chronic inflammation is charactrized by
Influx of macrophages and lymphocytes as opposed to neutrophils in acute response
By build up of fibroblasts rather than exudate which leads to risk of scarring
Nonspecific inflammation
Diffuse accumulation of macrophages and lymphocytes
Continual chemotaxis
fibroblast proliferation
scar formation
Granulomatous inflammation
Mass of macrophages surrounded by lymphocytes
Insulting agent was poorly controlled by other inflam mechs
CT eventually encapsulates mass
Example would be TB
Systemic manifestations
Body tries to control inflammation to local, if it does go systemic it is characterized by THREE features Acute-phase response WBC response Lymphadenitis (swollen members) Severe systemic is cytokine storm
Acute phase response
From cytokines systemic Increased C reactive protein* Eleveated CSR* Skeletal muscle catabolism Negative nitrogen balance Fever, anorexia, somnolence, malaise
WBC response in systemic
Bacterial infections produce increase in neutrophils
Parasitic and allergic responses produce increase in eosinophils
Viral infections produce decrease in neutro increase in lymphocytes
Leukocytosis
increased WBC
decreased is leukopenia
Lymphadenitis
Lymphs responsible for draining inflammation
Either due to immunologic response to specific antigen or a generalized response to chemical medatiors in the inflammation
Cytokine storm
Massive release of chemical mediators into body SIRS
Tissue repair
Tissue regen - replacement with same cells
Fibrous tissue - replacement with CT (scar)
Healing is regulated by
chemical mediators, ECM, and growth factors
Growth factors
Hormone-like molecules interact with specific cell receptors, control proliferation, differentiation, metabolism of cells during healing process
Also regulate inflammatory process, act as chemo attractants, stimulate angiogensis, help form ECM
Cells involved in wound healing
Leukocytes Macrophages Epithelial cells CT (myofibros, angio, and fibro -blasts) Tissue rich in those ^ is granulation tissue
Primary vs secondary intention
Small close wounds heal by primary
Large spaced out ones are secondary
3 phases of wound healing
Inflammatory
Proliferative
Remodeling
Inflammatory phase of healing
Prepares environment
Needs proliferation of chem mediators and growth factosr
Proliferative Phase
Formulation of granulation tissue (fibro, myofibro, angioblasts)
Epithelization also occurs (migration, prolif, and differentiation of epithelial cells at wound edges to form new layer)
Remodeling phase of wound healing
Type 3 collagen replaced with Type 1, done to increase overall strength of wound
Factors affecting wound healing
Nutrition Blood flow Impaired inflammatory or immune resonses Infecction Wound seperation Foreigners
Complications of bad wound healing
Loss of founction Contractures (perm shortening of muscle or joint) and obstruction Adhesions Hypertrophic scar tissue (keloid -elevated scars) Ulcerations Wound dehiscence Infection Delayed healing
