Acute Inflammation Purpose and Process Flashcards
1
Q
Inflammation
A
- The host response to injury
- vascular and cellular events
- It is complex and integrated response involving the microvasculature, blood elements, and local ECM
- Overlaps with other host responses
- hemostasis and immunity
- Essential for life, but can have adverse consequences
- can last for hours or years
2
Q
Inflammation:
Causes
A
- Microorganisms
- Chemicals
- Trauma
- Thermal or Radiation injury
- Foreign Bodies
- Immune Reactions
- Necrosis
- Neoplastic/altered cells
3
Q
Inflammation:
Purpose
A
- To isolate, dilute, neutralize, confine and remove the offending agents
- To clear the area of debris
- To initiate healing and repair
4
Q
Inflammation:
Outcomes
A
- Elimination of the agent and return to normal
- Stalemate: Ongoing inflammation
- Death of the host
5
Q
What do you see
A
Lung, dark red, dry,
6
Q
What do you see
A
Larynx and Abomasum, swelling
7
Q
Cardinal Signs of Inflammation
A
Rubor (redness)
Tumor (swelling)
Calor (heat)
Dolor (Pain)
8
Q
5th sign of Inflammation
A
- Function Laesa (Loss of Function)
- Added by Rudolf Virchow about 1860
9
Q
Inflammation:
Learn about it by investigating
A
Vascular changes
Cellular Events
Chemical mediators
Duration
Acute vs. chronic
10
Q
Inflammation:
Vascular Events descovery
A
- The pattern of vascular change associated with acute inflammation was originally described in 1867 by Julius Cohnheim
11
Q
Inflammation:
Review of the Microcirculation
A
- Blood flow is not constant through the microcirculation
- Flow is usually determined based on physiologic needs
- It also changes following injury
12
Q
Inflammation:
Vascular Events
A
- Sequential series of vascular events in response to inflammation are:
- Transient arteriolar vasoconstriction
- Arteriolar vasodilation
- Capillary congestion
- Increased vascular permeability
- Slowing of blood flow
- Redistribution of blood cell elements
- Blood flow stasis
13
Q
Transient Arteriolar Vasoconstriction
A
- Caused by the direct effect of the inciting stimulus on arteriolar smooth muscle
- regulated by the release of local mediators
- This does not occur with all stimuli
- Vasoconstriction lasts several seconds, up to 5 minutes
14
Q
Arteriolar Vasodilation
A
- A wave of vasodilation starting at the arteriole progressing to the venule causes hyperemia
- mediators of vasodilation
- Histamine
- Bradykinin
- Prostacycline
- Prostaglandin D2
- Leukotriene B4
- Nitric Oxide
- Local Neurogenic substances
- mediators of vasodilation
15
Q
Increased Vascular Permeability
A
- Endothelial junctions become leaky resulting in fluid and molecule loss to the interstitium
- Mediators include:
- Immediate stranseint response:
- histamine, bradykinin, Leukotrienes B4C4D4E4, Platelet activating facotr, C3a and C5a, Substance P
- Delayed sustained response:
- TNF, IL-1, Gamma-IFN
- Immediate stranseint response:
- Mediators include:
16
Q
Increased Vascular Permeability:
Edema Factor
A
- This was one of our mechanisms for edema
- increased intravascular hydrostatic pressure, and increased extravascular osmotic pressure also contribute to fluid loss
- Fluid that moves into the extravascular space contains proteins involved in inflammation and helps to dilute the inciting stimulus
- Fluid changes in character form a transudate to an exudate
17
Q
Slowing of Blood Flow
A
- Due to large vascular diameter resulting in slower flow and increased numbers of bood cells
- Increased blood viscosity due to plasma loss
- Increased Adhesiveness or erythrocytes
18
Q
Redistribution of blood cell elements
A
- Laminar flow is disrupted due to vasodilation and congestion
- Erythorcytes become ventrally located
- Leukocytes move to the periphery along the endothelaial surface
- THis relocation is essential to begin the cellular changes associated with inflammation
19
Q
Inflammation:
Cellular Events
A
- Critical Event in inflammation is the movement of cells from the blood vessel to the site of injury
- Major steps include:
- Margination and adhesion of endothelium
- Emigration
- Chemotaxis
- Accumulation
20
Q
Margination and adhesion to endothelium:
A
- A vascular event that moves leukocytes to the periphery to the vessels; adjacent to the endothelium
- Initially, leukocytes transiently adhere (roll) along the endothelial surface
- mediated by endothelial E- and P-selectins
- Mediated by leukocyte L-selectin
- Later, leukocytes firmly adhere to endothelium
- Endothelial Receptors:
- Intercellulr Adhesion Molecule -1 (ICAM-1)
- Vascular Cell Adhesion Molecule-1 (VCAM-1)
- Leukocyte receptors:
- B-2 integrins
- Increased expression on activated leukocytes
- B-2 integrins
- Endothelial Receptors:
21
Q
Leukocytes adhesion molecules
A
B-2 integrins include:
Mac-1, LFA-1, P150,95 and adB2
All of these share a B-subunit CD18
22
Q
Emigration
A
- The movement of leukocytes form the endothelial surface into the extravascular space
- facilitated by the enlarged gaps between endothelial cells
- Leukocyte-endothelial interactions occur within the inter-endothelial junction
- Active mobility of leukocytes enable them to exert pseidopods into inter-endothelial junctions to pull themselves throug the extravascular space
23
Q
Emigration:
Order
A
- Neutorphils emigrate first
- Initial emigration can occur within 30-40 minutes of the stimulus and predoinate for 6-24 hours
- Monocytes emigrate next
- predominate by 24-48 hours
- Lymphocytes are sluggish
- Don’t emigrate until later
24
Q
Chemotaxis
A
- the directed movement of leukocytes to the site of an inflammatory stimulus
- occurs in response to a concentration gradient of a chemkcal attraction
- activated complement components
- Bacterial products
- Arachidonic Acid metabolites
- Kinins
- Collagen and fibrin breakdown products
- Leukocyte production
- Chemotaxis
- occurs in response to a concentration gradient of a chemkcal attraction
25
Q
Chemotaxis:
Mechanisms
A
- Chemotactic factors interact with specific leukocyte membrane receptors
- Membrane phospholipase C is activated and results in localized release of Ca2+ in the cytoplasm
- Fluxes in Ca2+ concentrations result in localized assembly and disassembly of microtubules and microfilaments
- Leukocytes B1 integrins bind to ECM components to pull themselves in the direction of the sitmulus
26
Q
Accumulation::
A
- Neutrophils are the first cell to accumulate at the site of the stimulus
- first to emigrate, most motile, are short-lived in the tissues
- Macrophages become more numerouse after 24-48 hours
- Emigrage later, but emigration is more sustainded
- Long lived and can replicate locally
- Lymohocytes may accumulate later in response to persistent immunologic stimuli
27
Q
What has been accomplished
A
Leukocytes have moved out of the blood vessels at the site of injury
Leukocytes have migrated through the ECM to the location of the inflammatory stimulus
28
Q
Inflammation:
Cellular Events:
Phagocytosis
A
- This is the uptake and degredation of particular material by leukocytes
- Neutrophils and macrophages are the most important phagocytes in inflammation
- Purpose:
- Destroy and remove the inflammation stimulus
- Clean up debris to stimulate the healling process
29
Q
Phagocytosis
A
- The process can be divided inot stages
- Opsonization
- Attachment
- Ingestion
- Killing and degradation
30
Q
Opsonization
A
- This is the coating of foreign material by factors that enhance phagocytosis
- Major Opsonins
- C3b
- IgG
- Collectins
31
Q
Attachment
A
- The phagocyte attaches to the foreign material
- Phagocytes readily attach the opsonized material
- phagocytes have specific membrane receptors for C3b and the Fc protion of IgG
- Phagocytes can attach to unopsonized material, but much less efficiently
- Phagocytes readily attach the opsonized material
32
Q
Ingestion
A
- Cell membrane pseudopods extend around the material to internalize it into an intra-cytoplasmic vacuole
- caled a phagosome
- Ingestion is an active process similar to that which occurs with chemotaxis
- Ca2+ fluxes regulate cytoskeletal changes
33
Q
Killing and Degradation
A
- A lysosome fuses to a phagosome to form a phagolysosome
- Lysosomal enzymes are relaeased itnot he phagolysosome
- If the material is a microorganism, it must first be killed
- Oxygen-independent killing mechanisms
- Oxygen-dependent killing mechanisms
*
34
Q
Oxgen-Independent Killing
A
- Mediators are the contents of lysosomes
- acid hydrolases
- Bactericidal permiability increased protien
- Major basic protein
- Lysozomes
- Lactoferrin
- Defensins
- Cathepsin G
35
Q
Oxygen-dependent Killing
A
- Increased oxygen uptake results in the production of a variety of oxygen metabolites
- Are highly reactive and potent killing agents
- Two Killing pathways
- Myeloperoxidase-indepent pathways
- Myeloperoxidase-dependent pathway
- Two Killing pathways
- Are highly reactive and potent killing agents
36
Q
Myeloperoxidase-Independent Pathways
A
- Killing mediated by the direct oxidative effects of oxygen metabolites
- Superoxide anion
- Hydrogen peroxide
- Hydroxyl radical
- Formation of NADPH oxidase during the respiratory burst initiates the process
37
Q
Myeloperoxidase-dependent Pathways
A
- H2O2 + Cl = HOCl
- hypochlorous acid: bleach
- Considered the most potent killing mechanisms
- Pathway is present in neutrophils, but plays an insignificant role in macrophages
38
Q
Digestion of the material
A
- Following killing, degradation
- Acid hydrolases and other proteolytic enzymes liquify the debris
- Unliquefied debris persists as a residual body
- Following phagocytosis, neutrophils undergo apoptosis and are removed
- Macrophages persist and continue to function at the site until no longer needed
39
Q
Phagocytosis:
What can go wrong?
A
- Some organisms survive within the phagolysosome
- some organisms are virulent to phagocytes
- timing errors in phagosomes-lysosome fusion may occur
- Large or indigestible substances can’t be internalized
- Reactive metabolites damage the cell
40
Q
Cellular Events:
What can go wrong
A
- Decreased circulating leukocytes
- Defective adhesion to endothelium
- Defective movement
- Defective phagocytosis
- Defective intracellular Killing
The result is a decreased host response to the inflammatory stimulus
