Acute and Chronic Inflammation Flashcards
1
Q
What is inflammation and what are 3 general ways that it provides a protective response?
A
- tissue response to damage or infections that bring host defense cells and molecules from the ciruclation to the site of damage
- Protective response bc:
- destroys/ contains harmful agent
- Prepares for occurence of healing/repair
- Without inflammation, infections and wounds would not heal
2
Q
What are the four cardinal signs of inflammation?
A
Calor (heat)
Rubor (red)
Tumor (swelling)
Dolor (pain)
Functio lase (loss of function0
3
Q
Describe the general sequence of events for an inflammatory reaction. 5 steps
A
- recognition by macrohages etc in cells and tissues
- mediators (amines, cytokines) released by macrophages, DCs and mast cells recruit leukocytes
- vasodilation and increased vascular permeability-leads to edema
- elimination of microbes and dead tissue by lymphocytes
- repair via cytokines and growth factors
4
Q
How are acute and chronic inflammation different? Describe:
onset
cellular infiltrate
tissue inury, fibrosis
local ad systemic signs
A
- ONSET
- Acute: fast minutes
- Chronic: slow days
- CELLULAR INFILTRATE:
- Acute: PMNs (neutrophils)
- Chronic: monoctes/macrophage and lymphocytes (T/B)
- TISSUE INJURY:
- Acute: mild and self limited
- Chronic: severe and progressive
- LOCAL AND SYSTEMIC SIGNS:
- Acute: prominent
- Chronic: less prominent, may be subtle
5
Q
Damage to the sit of injury/adjacent normal tissue may occur. What are 4 ways which this can occur?
A
- acute inflammation: resolves w/o permanent damage
- long standing infection (chronic): permanent damage possible
- autimmune disease (ex lupus)
- Allergies: inflammation against something that should be a toleragen
6
Q
What recognizes abnormal stimulus in the body?
A
- Cells with receptors that detect the presence of infectous pathogens (Epithelial cells, Dendritic cells, phagocytes, and usually the receptor is a TLRs)
- sensors of cell damage that are activated by: uric acid, ATP, reduced intracellular K, cytosolic DNA. The sensors activate inflammasome
- circulating complement proteins
7
Q
What is inflammasome?
A
- sensors of cell damage would activate it
- cytoplasmic complex recognizing parts of dead cells that trigger the activation of caspase-1 which activates IL-1 triggering leukocte recruitment
8
Q
What are the three components of actue inflammation? (what things change)
A
- Dilation of small vessels
- increased permebility of small vessels (influenceing lymph vessels & nodes)
- Emigration of leukocytes from circulation, leukocyte activation
9
Q
Describe how dilation of small vessels occurs during acute inflammation. What does this lead to?
A
- histamine and NO induce vasodilation
- first affects arterioles then capillary beds
- vasodilation leads to stasis of flow/congestion resulting in erythema and calor
- margination of leukocytes
10
Q
How does vascular permeability increase during acute inflammation?
A
- endothelial cell contraction due to histamine and bradykinin
- predominately affect venules
- You might also get endothelial cell injury from burns or things traveling through it-increased transcytosis
11
Q
How do lymph vessels respond to acute inflammation?
A
- edema fluid and cellular debris drain
- sometimes secondary lymphandentitis occurs
12
Q
What is edema?
A
- excess fluid in interstitia, or serosal cavities
*
13
Q
WHat is transdudate?
A
- Hypocellular and low protein contetnt leading to fluid leakage
- ex: non-inflammatory extravascular fluid, ultrafiltrate or plasma with a low specici gravity
- Usually not from inflammation but is from liver failure or heart failure. whereas exudate is typically from inflammation/trauma. less serious thatn exudate. increased hydroststaic or decreased colloid pressure.
14
Q
What is Exudate? What causes it?
A
- cellular (white and RBCs) and protein rich
- inflammatory extravasculr fluid with high specific gravity
- caused by alteration in normal vessel permeability usually from inflammation
- this is more serious than transudate which doesn’t have much more than fluid.
15
Q
What is pus?
A
pirulent exudate rich in leukocytes-infected
16
Q
Histamine:
where is it released from, in response to what, and what does it cause?
A
HIstamne:
- released from mast cells in connective tissue near vessels
- released in response to IL-1, trauma, complement
- causes vasodilation and increases vascular permeability
17
Q
Nitric Oxid (NO) where is it released from, in response to what, and what does it cause?
A
- released by endothelial cells in response to injury and causes vasodilation
18
Q
Bradykinin where is it released from, in response to what, and what does it cause?
A
Bradykinin is a plasma protein resulting from activation of kinin system due to exposure to a site of endothelial injury. leading to vasodilation, increased permeability and ***pain***
19
Q
What is the origin of neutrophils
A
from hematopoetic stem cell marrow
20
Q
What is the origin of macrophages
A
- from hematopoietic cells in marrow (in inflammatory reactions)
- many tissue resident macrophages (stem cells during development)
21
Q
WHat is the life span of neutrophils?
A
1-2 days
22
Q
What is the life span of macrophages?
A
inflammatory macrophages: days or weeks
tissue-resident macrophages: years
23
Q
How do neutrophils respond to stimuli?
A
rapid, short-lived responses
24
Q
how do macrophages respond to stimuli
A
more prolonged, slower, dependent on new gene transcription
25
Describe how leukocytes ahere to th endothelium
* leukocytes marginate close to wall as the blood flow slows (due to vasodilation)
* Molecules roll and adhere to endothelial cels with the help of adhesion molecules
* Selectins: on endothelial cells, platelets, leukocytes
* Integrins: on leukocytes
26
WHat is the role of selectin/how does it work?
* exists on endothelial cells, pltelets, leukocytes
* P-selectin, L-selectin etc.
* not present on cell surfaces until cell activated by mediators ( histamine, thrombin, etc.
* aid in rolling and **loose** attachment to endothelial cells
27
What is the role of integrin and how does it work?
* integrin is on leukocytes
* activated by expression of chemokines on endothelial cells
* TNF and IL-1, secreted by macropages at the site of injury, increase endothelial cell ligand expression
* results in **stable** attachment of leukocytes to endothelium
28
What is the difference in attachment between selectin and integrin?
selectin aids in loose attachment and integrins aid in stable attachment
29
What is DIapedesis?
movement of leukocyte through vessel wall
30
Describe the process of transmigration in actue inflammation
* leukocytes squeeze between endothelial walls
* this is driven by chemokine: **CD31 (PECAM)** on leukocytes and endothelial cells
31
How is chemotaxis involved in acute inflammation?
* Chemotaxis is the movement along a chemical gradient
* after crossing the vessel wall, cell migrate towards the injury site based upon chemotactic factor like **chemokines, complement and leukotrienes**
32
Leukocytes are involved in acute inflammation. What activates them? when does activation occur and what are the 4 results of leukocyte activation?
* Leukocytes are nuetrophils and macrophages
* they are activated by microbes, necrotic tissue, mediators
* activation occurs after recruitment to site of injury
* the results are:
* Phagocytosis
* intracellular destruction
* release of substances that destroy dead tissue and microbes
* more mediator production (amplify inflammatory reaction)
33
How does phagocytosis occur in inflammation?
* leukocyte recognizes a microbe via a specific surface receptor or **opsonins** marking the microbe as a target
* Engulfment and formation of pahgocytotic vacuole within leukocyte and fusion with a lysosome
34
How are microbes are killed and degraded?
within a phagolysosome via **ROS** and leukocytes secreting enzymes into the extracellular space to degrade microbes and dead tissue
35
What mediators are associated with vasodilationand what is the source?
HIstamine, Nitric Oxide
Source: mast cells, basophils, platelets, endothelium, macrophages, mast cells, leukocytes
36
What mediators are associated with increased vascular permeability?
histamine, bradykinin
source: mast cells, basophils, platelets, plasma, leukocytes
37
What mediators are associated with chemotaxis, leukocyte recruitment and activation
IL-1, TNF, Bacterial products
38
What mediators are associated with fever?
IL-1, TNF
source: macrophages, endothelial cells, mast cells
39
What medators are associated with pain?
bradykinin
source: mast cells, leukocytes, plasma
40
What mediators are associated with tissue damage?
Reactive oxygen species, NO
41
Describe the key steps in acute inflammation
1. Recognition of injurious agent by receptors on epithelial cells and endothelial cells
2. initiation of the inflammatory response: release of Il-1 and TNF activates endothelial cells
3. Recruitment of leukocytes:
1. margination: leukocyte accumulation at periphery of vessels
2. RollingL weak and transient adhesions to endothelium (selectins)
3. Adhesion: firm adhesion to endothelium (Integrins)
4. Transmigration: movement through endothelium to interstitium (CD31)
4. Leukocytes move towards site of infection (chemotaxis) and are activated by microbes, necrosis, mediators
5. Phagocytosis and killing
42
What are the 3 causes of leukocyte functional defects?
* defect in leukocyte production: bone marrow suppression due to chemotherapy and/or radiation
* defect in adhesion and chemotaxis: sepsis, diabetes, dialysis, malignancy
* defect in phagocytosis and microbial activity: sepsis, diabetes, anemia, malnutrition
43
How does acute inflammation resolve?
* Resolution:
* mediators degrade
* vascular permeability returns to normal
* neutrophils die (by apoptosis)
* debris cleared by macrophages
* OR progession to chronic inflammation
* OR scarring or fibrosis
44
What does the morphology of inflammed tissue reflect?
severtity of inflammation, specific cause, and tissue affected
45
What are general conditions of all actue inflammation?
* accumulation of leukocytes (neutrophils and macrophages) and fluid in extracellular tissue
* dilation of small blood vessels
46
List the 3 subtypes (morphologic patterns) of inflammation
* serous
* fibrinous
* suppurative
47
Describe Serous inflammation and list examples
* Mildest form of acute inflammation
* outpouring of thin fluid (very few cells or proteins) from plasma or serosal cavity linings due to injury of surface epithelia
* examples:
* peritoneal, pleural, or pericardial effusions-CHF, fluid overload
* **Skin blister from burn**, viral infection or trauma
48
Describe Fibrinous inflammation and list examples
* occurs secndary to more severe injury
* larger vascular leaks, passage of fibrinogen, conversion to fibrin
* affects linings: _meninges, pericardium, pleura, peritoneum_
* May resolve completely or may organize leading to scarring
* examples:
* fibrinous pericarditis from uremia, a transmural myocardial infarct, or acute rheumatic fever
* fibrinous pleuritis
* fibrinous peritonitis
49
Describe suppurative (purulent) inflammation
* when large numbers of neutrophils are present along with necrotic cells, edema fluid, bacteria, usually liquified and called _PUS_
* occurs with infections: pyogenic bacteria are most llikely (ex staph)
* abscess
* ex: acute appendicitis, acute bronchopneumonia, acute meninngitis
50
What is an abscess?
central area of necrotic tissue surrounded by preserved neutrophils, dilated vessels and fibroblastic proliferation
51
What is an ulcer?
* local defect
* surface of organ or tissue
* sloughing of surface covering and necrotic inflammatory tissue
* occurs when tissue necrosis and inflammation are present on or near a surface (skin, GI tract) may be acute or chronic
* ex: pepic ulcer, skin ulcer
52
What kind of inflammation is this?
* fibrous inflammation
* usually caused by uremia
53
What kind of infection is this?
suppurative
Look at all of the neutrophils!
54
Please summarize the initation of inflamm response
* recognition of injury by cell recepors resulting in cytoking ( Il-1, TNF) production and leukocyte recruitment
55
What causes chronic inflammation?
* persistent infection
* prolonged exposure to toxic agents
* hypersensitivity disease: autoimmune, allergy
56
What is chronic inflammation characterized by?
* infiltration by mononuclear cells: macrophages, lymphocytes and plasma cells
* tissue destruction from continous inflammation
* attempts at healing: angiogenesis (blood vessel formation) and fibrosis (deposition of collagen)
57
What is the role of macrophages in chronic inflammation?
* macrophages persist bc of release of dead cells and stimulation by cytokines
* they secrete products that result in continued tissue injury
58
How are lymphocytes involved in chronic inflammation?
* amplify and propagate chronic inflammation
* T&Bs migrate to site and Plasma cells produce immunoglobi against persistent antigen and there is bidirectional interaction with macrophages
59
What is the role of eosinophils in chronic inflammation?
parasitic infection and IgE mediation inflamation (allergies) using Major basic protein
60
WHat are mast cells
* they are found in conenctive tissue
* they have a receptor for IgE that is specific for environmental antigen and release histamine and arachidonic acid metabolites and they are central in allergies
61
What are the morphologic features of chronic inflammation?
* mononuclear cell infiltrates-macrophages, lmphocytes, plasma cells
* tissue destruction
* attempted tissue repair: angiogenesis and fibrosis
62
Describe granulomatous inflammation
* aggregate of epithelioid histocytes (macrophages)
* multinucleated giant cells
* fusion of many macrophages, **IFN-y** induces giant cell formation
* surrounding fibrosis
* in TB: central caseous necrosis
63
What is this arrow showing?
Angiogenesis
64
What type of inflammation is typically seen in appendicitis?
acute suppurative inflammation
* neutrophils through wall surface
* no giant cells usually
65
What are the systemic effects of inflammation?
* Called acute phase response
* fever
* elevated levels of acute-phase proteins
* leukocytosis
66
What type of inflammation is this?
granulomatous- bc you can se the giant cell!
67
WHat causes a fever and what does a fever cause?
* in response to pyrogens both exgenous (endotoxins lipopolysaccharides) and endogenous (Leukocytes release IL-1 and TNF)
* cause production of prostaglandins (PGE2) which stimulate the hypothalamu to repeat higher temepratures
68
What are the effects of acute phase proteins in inflammation?
* C-reactive protein, firbinogen
* bind to microbe wall to aid in elimination
* fibrinogen binds to erythrocytes causing stacks that sediment more rapidly than normal and therefore increased sed rate is used to monitor activity of inflammation
69
What is leukocytosis?
* stimulated by TNF, IL-1
* WBC count is high (15,000-20,000)
* neutrophilia-bacterial infection
* lymphocytosis-viral infections
* eosinophilial allergies, asthma, prasitic infections
* Leukopenia-typhoid, rickettsiae
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