Acute Inflammation Purpose and Process Flashcards
(40 cards)
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
Chemotaxis:
Mechanisms
* 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
Accumulation::
* 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
What has been accomplished
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
Inflammation:
Cellular Events:
Phagocytosis
* 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
Phagocytosis
* The process can be divided inot stages
* Opsonization
* Attachment
* Ingestion
* Killing and degradation
30
Opsonization
* This is the coating of foreign material by factors that enhance phagocytosis
* Major Opsonins
* C3b
* IgG
* Collectins
31
Attachment
* 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
32
Ingestion
* 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
Killing and Degradation
* 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
Oxgen-Independent Killing
* Mediators are the contents of lysosomes
* acid hydrolases
* Bactericidal permiability increased protien
* Major basic protein
* Lysozomes
* Lactoferrin
* Defensins
* Cathepsin G
35
Oxygen-dependent Killing
* 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
36
Myeloperoxidase-Independent Pathways
* 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
Myeloperoxidase-dependent Pathways
* 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
Digestion of the material
* 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
Phagocytosis:
What can go wrong?
* 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
Cellular Events:
What can go wrong
* 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
