Exam 3: Acute Inflammation Flashcards
What is inflammation?
The response of living tissue of injury
What does inflammation involve?
A well-organized cascade of fluidic and cellular changes
Describe the process of inflammation
Process is redundant and complex
Process is continuous over a period of time
What is the primary delivery system for inflammatory components?
Blood
What is acute inflammation?
Standardized reaction, early response
Immediate vascular response
What is chronic inflammation?
Alteration of an inflammatory response
Weeks to years
What can both acute and chronic inflammation occur due to?
Microbes or non-infectious reasons
What is the goal of acute inflammation?
Dilute toxins
Isolate
Eliminate
Repair
Describe diluting toxins with acute inflammation
Biological and chemical
Add fluid to it
Describe isolation with acute inflammation
Sequester microbes, foreign material, dead tissue
Describe elimination with acute inflammation
Kill/remove inciting cause
Describe repair with acute inflammation
Remove necrotic cells, recruit reparative cells and factors
Is fibrin acute or chronic?
Acute
What are harmful effects of inflammation?
Persistent cytokine release
Destruction of normal tissue
Swelling
Inappropriate inflammatory response
What are systemic effects of inflammation?
Leukocytosis
Fever
What is leukocytosis?
An abnormally high number of circulating white blood cells
What do increased neutrophils often indicate?
A bacterial infection
What are increased lymphocytes associated with?
Viral infections
Describe fever
Coordinated by the hypothalamus and involves a wide range of factors
What is fever commonly associated with?
An infectious cause
What are the cardinal signs of inflammation?
Heat Redness Swelling Pain Loss of function
What is heat?
Increase in temperature due to increased blood flow
What causes redness?
Dilation of small blood vessels within an area (hyperemia)
What is swelling a result of?
Edema
What is pain due to?
Stretching and distortion of tissues (due to edema and chemical mediators)
What is loss of function?
Movement inhibited by pain or swelling
What are exogenous stimuli of inflammation?
Microbes
Foreign bodies
Injury: chemical, thermal, heat, ischemia
What are endogenous stimuli of inflammation?
Autoreactive- newly developed antigens from degenerate or neoplastic cells
Hypersensitivity reactions
What do the stimuli of inflammation cause?
Activation of the innate immune response
Describe nonspecific defense of the innate immune response
Physical barriers: epithelial surfaces, ciliated cells, secretion
Molecular products: secreted by epithelial cells
Chemical mediators from effector cells within connective tissue of the barriers
What are the characteristics of acute inflammation?
Recognition of injury/pathogen
Send inflammatory cells: microvascular exudation of electrocytes, fluid, and plasma proteins (fluidic phase); leukocyte emigration (cellular phase)
Send effector molecules
Repair and heal (reparative phase)
How does the body recognize invaders (microbes and damaged cells)?
Cellular receptors
Cellular sensors
Circulating proteins
What are innate immune cells able to do?
Recognize certain components from microbes and from damaged/dead tissue
What are the different cellular receptors on immune cells?
Receptors on the plasma membrane
Cyctosolic receptors
Receptors on the endosome
What happens when TLRs recognize microbial molecules?
Induction of pro-inflammatory cytokines and type I interferons
What does TLR4 do?
Bind to LPS of gram-negative bacteria
What are pattern recognition receptors?
PAMPs
DAMPs
Describe PAMPs
Pathogen-associated molecular patterns
Microbial structures
Describe DAMPs
Danger-associated molecular patterns
Released from necrotic cells
What are NOD-like receptors?
Cytosolic receptors that recognize a diverse set of molecules
What do NOD-like receptors activate?
The inflammasome
Describe the inflammasome
A multiprotein complex
Induces production of IL-1
What does IL-1 do?
Recruit leukocytes
Describe C-type lecitn receptors
On the plasma membrane
Detect fungal glycans and elicit inflammation to fungi
Describe Fc
Leukocytes express the receptors for Fc tails of antibodies for complement proteins
Recognize opsonized material
Describe circulating proteins
Complement: reacts against microbes and produces mediators of inflammation
What are mediators of inflammation?
Substances secreted by cells that initiate and regulate inflammatory reactions
What are mediators of inflammation secreted by?
Primarily macrophages, dendritic cells, and mast cells
What can happen to mediators of inflammation?
Sequestered in intracellular granules for rapid secretion OR may be synthesized de novo
What are mediators of inflammation produced in response to?
Various stimuli
What do mediators of inflammation bind to and what do they do?
Bind to receptors on target cells to secrete additional inflammatory mediators
What are the checks and balances of mediators of inflammation?
Have short half-lives and quickly decay
Are enzymatically destroyed
Are scavenged by antioxidants
Describe inflammatory mediators from plasma proteins
They are constantly being secreteed by the liver as precursors
Activated via proteolytic cleavage in circulatory system
Look at inflammatory mediators chart
Look at inflammatory mediators chart
What are examples of preformed inflammatory proteins?
Histamine
Serotonin
What produces histamine?
Mast cells
Basophils
Platelets
What does histamine do?
Vasodilation
Increased vascular permeability
What produces serotonin?
Mast cells
Platelets
What are the functions of serotonin similar to?
Similar to histamine’s functions
What are the synthesized mediators?
Cytokines
Chemokines
Arachidonic acid metabolites
What are cytokines?
Proteins produced by many cell types (primarily macrophages, lymphocytes, dendritic cells)
What stimulates production of cytokines?
Extrinsic and intrinsic factors
What is the function of cytokines?
Regulate immune and inflammatory reactions
What are the cytokines release with acute inflammation?
TNF, IL-1, IL-6
What are the actions of cytokines?
Endothelial activation
Leukocyte recruitment
Leukocyte activation
Systemic acute phase response
What are chemokines?
Cytokines that promote leukocyte chemotaxis and migration
What is an example of a chemokine?
IL-8
What does IL-8 do?
Chemotaxis of neutrophils
What are arachidonic acid metabolites?
Lipid mediators, prostaglandins and leukotrienes, produced from arachidohic acid present in membrane phospholipids
How are arachidonic acid metabolites released?
Mechanical, chemical, physical stimuli releases AA from the membrane
What are arachidonic acid derived mediators?
Prostaglandins
Leukotrienes and lipoxins
What is the function of arachidonic acid metabolites?
Mediate virtually every step of acute inflammation
Which arachidonic acid metabolites cause vasodilation?
Prostaglandins
Which arachidonic acid metabolites cause vasoconstriction?
Leukotrienes, thromboxane
Which arachidonic acid metabolites cause increased vascular permeability?
Leukotrienes
Which arachidonic acid metabolites cause chemotaxis and leukocyte adhesion?
Leukotrienes
What is the complement system?
Collection of soluble proteins and membrane receptors that function in host defense
Where are complement proteins present in their inactive forms?
Plasma
What are the functions of the complement system?
Inflammation
Opsonization and phagocytosis
Cell lysis
How does the complement system cause inflammation?
C3a and C5a are cleavage products
Stimulate histamine release (anaphylatoxins)
C5a: chemotactic for leukocytes
How does the complement system cause opsonization and phagocytosis?
C3b: when fixed to microbial cell wall, acts as opsonin and promotes phagocytosis
How does the complement system cause cell lysis?
Deposition of the membrane attack complex
Kills by making cells permeable to water—> lysis
What does activated factor XII do?
Activates the intrinsic coagulation and catalyzes the formation of kallikrein
Describe Bradykinin
Short lived
Increased vascular permeability
Vasodilation
Pain
What does Kallikrein do?
Acts on plasminogen to form plasmin and cleaves C3
What do fibrin polymers do?
Provide a surface or network to facilitate phagocytosis and prevent spread of infectious agents
What does excessive fibrin do?
Obstructs the microvasculature resulting in ischemic injury
What does excessive activation of the fibrinolytic system do?
Leads to depletion of fibrinogen and possibly hemorrhage
What are oxygen-derived free radicals released from?
Neutrophils and macrophages following exposure to chemokines and after phagocytosis
What can oxygen-derived free radicals do?
Alter signaling molecules
What is nitric oxide synthesized by?
Endothelial cells and macrophages
What does nitric oxide do?
Vasodilation
Inhibits platelet aggregation and adhesion
Oxidizes lipids
Describe platelet-activating factor
Phospholipid derived mediator
Many cells can elaborate the factor
Vasoconstriction and bronchoconstriction
Know role of mediators in different reactions of inflammation
Know role of mediators in different reactions of inflammation
What is the function of the fluidic phase?
Dilute and localize the stimulus
What is the sequence of vascular events in the fluidic phase?
Increased blood flow:
—Mediators- several but most notably histamine
—Vasodilation of arterioles leads to opening of capillary beds—> increased blood flow
Heat and redness
Increased permebaility of capillaries and postcapillary venules:
—Loss of fluid increased vessel diameter—> slower blood flow, concentration or red cells and increased blood vicosity
Swelling
What is the mechanism of increased vascular permeability?
Retraction by contraction of actin/myosin filaments or reorganization of the cytoskeletal microtubule and proteins
Endothelial cell necrosis and detachment
Activates platelets, clotting, and complement
Describe serous fluid
Clear watery fluid
Low concentration of plasma proteins with no or low number of leukocytes
What does serous fluid result from?
Increased vascular permeability
What does serous fluid suggest about the injury?
That is rather mild or peracute
How does serous fluid look histologically?
Affected tissues are spread apart by the watery fluid
What is fibrinous inflammation?
Term used to describe a pattern of acute inflammation
What is fibrinous inflammation caused by?
Infectious etiologies
What happens in fibrinous inflammation?
Accumulation of fluid with a high concentration of plasma protein (exudate)
Leakage of large molecular weight proteins (fibrinogen)
Fibrinogen polymerizes to form fibrin
What is seen grossly with fibrinous exudate?
Surface of affected tissue is often red
Early- surface may be granular and dull
Surface covered with a thick, stringy, white-gray to yellow material that can be easily removed
What is seen microscopically with fibrinous exudate?
Eosinophilic proteinaceous material- often fibrillary
In many cases, rapidly becomes infiltrated by neutrophils—> fibrinosupparative exudate
What is the consequence of fibrinous inflammation?
May resolve without any sequelae
If extensive, fibroblasts may migrate in and being organizing exudate—> fibrous adhesions
What is the function of cellular phase?
Deliver leukocytes to the site in order to kill and/or digest the stimulus
Describe the leukocyte adhesion cascade
Movement of leukocytes from vessel into the connective tissue
Driven by chemokines, cytokines, and chemoattractant substances
When is the leukocyte adhesion cascade initiated?
During the fluidic phase
What occurs during the cellular phase?
Margination
Rolling
Adhesion to endothelium
Migration
What is margination?
Leukocytes move to periphery of the vascular lumen in apposition with endothelial cell
What is pavementing?
When the surface of the endothelium becomes line by leukocytes
What is rolling?
Leukocytes adhere transiently to endothelium
What is adhesion to endothelium?
Firm adhesion
What is migration?
Migration through the endothelium and then to the stimulus
What is rolling and adhesion mediated by?
Adhesion molecules expressed on leukocytes and endothelial cells
What is the expression of rolling and adhesion enhanced by?
Cytokines
Where does leukocyte migration through endothelium occur?
Mainly in post-capillary venules
What stimulates cells to migrate?
Chemokines
What causes cell to migrate towards a stimulus?
Chemical concentration gradient (chemotaxis)
What happens during chemotaxis?
Leukocytes move toward the site of injury
Exogenous and endogenous substances act as chemoattractants
What are common exogenous substances?
Bacterial products and some lipids
What are common endogenous substances?
Cytokines (IL-8), components of complement system, arachidonic acid metabolits
What determines which cells are the first to arrive?
The stimulus
When are neutrophils the first cells to arrive?
In bacterial infection
When are lymphocytes and plasma cells the first to arrive?
In some hypersensitivity reactions
Lymphocytes are also the first with viral infections
When are eosinophils the first cells to arrive?
In allergic reactions
What is purulent inflammation?
Term used to describe a pattern of acute inflammation
What does the response of purulent inflammation consist of?
Accumulation of fluid with high concentration of plasma protein and high number of neutrophils
What is pus?
An accumulation of dead neutrophils
What is plegmon?
Pus distributed in tissue layers or along tissue layers
Also called cellulitis
What dpes purulent inflammation look like grossly?
Surface or connective tissue is hyperemic with thick white to gray to yellow material
When is purulent inflammation white?
If neutrophils are the predominant component
When is purulent inflammation yellow?
If there is a lot of necrotic debris
What is the consistency of purulent inflammation?
May be watery, creamy, or firm depending on the species and the inciting agent
What is fibrinopurulent?
When purulent inflammation is mixed with fibrin
What is seen microscopically with purulent inflammation?
Large numbers of neutrophils
May degenerate neutrophils and mixed with necrotic debris, tissue debris, plasma proteins, and fibrin
What is the significance of purulent inflammation?
Neutrophils are there to neutralize the offending agent
What is the outcome of purulent inflammation?
Neutralize
Form pus—> resorption of pus
May progress to chronic inflammation
What is an abscess?
A circumscribed collection of pus surrounded by connective tissue capsule
What is a systemic acute phase response with TNF, IL-1, and IL-6?
Fever
Increase production of leukocytes by the bone marrow
What is fever mediated by?
Prostaglandins that are increased int the hypothalamus
How does fever occur?
Cytokines increase cyclooxygenases that convert AA to prostaglandins
How do NSAIDs reduce fever?
By inhibiting prostaglandin synthesis
What does increased production of leukocytes by the bone marrow result from?
Mobilization of neutrophils from storage pools in bone marrow
What is the systemic acute phase response with TNF?
Energy balance
What is the systemic acute phase response with IL-1 and IL-6?
Stimulate acute phase protein production by the liver
What are the acute phase proteins?
C-reactive protein
Serum amyloid A
Fibrinogen
What do C-reactive protein and serum amyloid A do?
Bind to microbial cells walls
Activate complement
What is septiciemia?
Clinically significant form of bacteremia complicated by toxemia, fever, malaise, and often shock
What results in sepsis or shock?
Systemic interaction of microorganisms and their products with hist cells and chemical mediators
What are the clinical manifestations of shock?
DIC
Hypotension and metabolic disturbances
Multiple organ failure and death
What are the gross findings with septicemia?
Fluid body cavity, pulmonary edema, petechial hemorrhages, congestion of the liver and intestine
What are the histology findings with septicemia?
Acute necrosis of renal tubules, centrolobular hepatocytes and cardiac myocytes
What are the 4 types of pneumonia?
Bronchopneumonia
Interstitial pneumonia
Granulomatous pneumonia
Embolic pneumonia
