PATHOLOGY- Essentials of general pathology - Review of inflammation and repair Flashcards
1
Q
What is inflammation
A
Response of vascularised tissue to injury
2
Q
What is the purpose of inflammation
A
- Get necessary components to site of injury
- To isolate / contain injury
- To destroy microbes / inactivate toxins
- To remove debris / prepare injury site for & intitiate repair
3
Q
Inflammation is critical for what
A
Normal tissue maintenance
4
Q
When can inflammation be harmful
A
Poorly controlled/regulated
Mis-detected -> harmless allergens, self-antigens
Stimulus persistent/ unable to irradicate
5
Q
What are the 2 forms of inflammation
A
Acute
Chronic
6
Q
Definition of acute inflammation
A
Rapid host response that delivers leukocytes and plasma proteins (e.g. antibodies / fibrinogen) to sites of infection or tissue injury e.g. necrosis
7
Q
Characteristics of chronic inflammation
A
Later onset
Longer duration
Lymphocytes/macrophages predominate
8
Q
What does acute inflammation result from
A
Infection
Necrosis
Immune reactions
FBs
9
Q
Characteristics of acute inflammation
A
Early onset
Short duration
Oedema
Neutrophils predominate
10
Q
2 components in acute inflammation
A
Vascular reactions
Cellular reactions
11
Q
Major features of acute inflammation
A
- Changes in vascular flow / vessel calibre (RUBOR / CALOR)
- Increased vascular permeability (vascular leakage) -> fluid exudate (TUMOR)
- Recruitment of leukocytes to site of injury / infection -> cellular exudate (DOLOR)
12
Q
What effect do the vascular changes have in acute inflammation.
A
Vascular changes maximise the movement of plasma proteins and inflammatory cells from the circulation in to the site of injury
13
Q
List the vascular changes that occur in acute inflammation
A
- VASODILATION
- Initial brief vasoconstriction
- ^Blood flow -> erythema (rubor) - ^ VASCULAR PERMEABILITY
- Retraction of endothelial cells
- Endothelial injury
- Leukocyte mediated vascular injury
14
Q
What is the result of the vascular changes that occur in acute inflammation
A
Escape of protein rich fluid (exudate) into extra vascular tissues -> fluid exudate -> oedema
15
Q
Proteins in the fluid exudate as a result of vascular changes in AI include what
A
Immunoglobulins and coagulation factors (including fibrinogen)
16
Q
What effect does an increase in fluid/protein loss lead to
A
Increased viscosity of the blood/rbc concentration
This decreases blood flow
Allows stasis to occur
17
Q
What is the role of stasis
A
Stasis facilitates leukocyte accumulation on vessel wall -> “extravasation”
18
Q
List the cellular changes that occur in acute inflammation
A
- Extravasation/emigration
- movement of leukocytes from vessels to the site of injury
- mainly neutrophils
19
Q
What are the 5 steps in extravasation
A
- Margination
- Rolling
- Adhesion
- Migration (diapedesis)
- Chemotaxis
20
Q
What is margination, rolling and adhesion mediated by
A
CAMs (Cellular adhesion molecules)
21
Q
Where are CAMs expressed
A
Endothelium or leukocytes
22
Q
What happens in margination
A
Vascular stasis causes neutrophils to move out from central axis towards vessel wall
23
Q
What happens in rolling
A
- Cytokines (e.g. TF/IL-1) from damaged tissue -> activate endothelial CAMS
- Neutrophil surface ligands interact with endothelial selectins -> ‘slowly roll’
24
Q
What happens in adhesion
A
High affinity integrins on neutrophils bind to integrin ligands on endothelium -> stop neutrophil on vessel wall
25
What happens in migration (diapedesis)
- Neutrophils move through intracellular junctions medicated by PCAM-1 / CD31
26
Characteristics of chronic inflammation
Later onset
Longer duration
Lymphocytes/macrophages predominate
27
What is the suffix for inflammation
-itis
28
What are the cardinal signs of inflammation the same as
The hallmarks of acute inflammation
29
what are the cardinal signs of inflammation
Heat
Redness
Pain
Swelling
Loss of function
30
List the sequence of events in inflammation (5 R’s)
Recognition
Recruitment
Removal
Regulation
Repair
31
What happens after migration
Chemotaxis
32
What is chemotaxis
- Neutrophils exit - site of injury
- Neutrophils follow a chemokine gradient -> "sniff out" source of inflammation
33
What can chemotaxis be mediated by
- Exogenous chemokines
* Bacterial products
- Endogenous chemokines
* Cytokines, complement
* Arachadonic acid metabolites
34
Once the neutrophils get to the site of injury, what are their 3 roles
- Phagocytosis
- Engulfment
- Killing / degradation
35
List the beneficial effects of fluid and cellular exudates in acute inflammation
* Dilution of toxins
* Entry of antibodies
* Enhanced drug delivery
* Fibrin formation
* Delivery of nutrients / 02
* Stimulation of immune response
36
List the harmful effects of fluid and cellular exudates in acute inflammation
* Digestion of normal tissues by released lysosomal enzymes
* Swelling e.g. epiglottitis / cerebral abscess
* Inappropriate / exaggerated immune response
37
List the morphological patterns in acute inflammation
SEROUS INFLAMMATION
- Exudation of cell-depleted fluid into body cavity e.g. pleural
- Fluid has few microbes / cells
FIBRINOUS INFLAMMATION
- Larger vascular leaks -> fibrinogen leaks out -> formation of fibrin
- E.g. fibrinous pericarditis
PURULENT / SUPPURATIVE INFLAMMATION
- Infection by bacteria that can destroy tissues (e.g. staph) -> lots of neutrophils / necrosis -> pus
- Abscess = localised collection of pus
ULCERATION
- Local surface defect due to sloughing / shedding of necrotic tissue
- e.g. Gastric ulcer
38
When does acute inflammation become chronic inflammation
Where there is a persistent causal agent
39
What are the characteristics of chronic inflammation
- Inflammation of prolonged duration - generally arising from acute
- Co-existent tissue destruction and repair
- Mononuclear inflammatory cells
40
What are the causes of chronic inflammation
- PROGRESSION from non-resolving acute inflammation
- PERSISTANT infection by certain microorganisms
- PROLONGED exposure to potentially toxic agents
- AUTOIMMUNITY
- UNKNOWN
41
Morphology of chronic inflammation
Mononuclear cell infiltration
- NOT neutrophils (acute)
- Macrophages / lymphocytes / plasma cells
Tissue destruction
- Persistent agent / inflammatory cells
Healing
- Damaged tissue -> fibro-proliferative repair
- Blood vessel proliferation
- formulation of ‘Granulation tissue'
42
What are the specific functions of macrophages in chronic inflammation
Phagocytic- ingest/eliminates dead tissues/microbes
Initiates tissue repair- stimulates blood vessels/fibroblasts which results in scar tissue/fibrosis
Secrete inflammatory mediators- contribute to initiation/propagation of inflammation
Interact with lymphocytes e.g. antigen presentation/feedback signals
43
What effect does granulomatous inflammation have on T cells
Increases T cell response (persistent)
This increases macroophages
This causes increased tissue damage
44
Examples of conditions that result in granulomatous inflammation
Tuberculosis
Leprosy
Syphilis
Cat-scratch disease
Sarcoidosis
Crohns disease/IBD
Industrial dust exposure
45
What does granulomatous inflammation look like microscopically
- Granuloma is a microscopic aggregation of macrophages transformed in to epithelium like cells
- collar of mononuclear leukocytes
-giant cells (20+ nuclei in large cytoplasmic mass, peripheral nuclei=langhans gc, haphazard nuclei= foreign body-type gc)
- older granulomas have a rim of fibroblasts/connective tissue
46
Define resolution
The complete restoration of normal tissue architecture without scarring through regeneration
47
Define regeneration
Process of proliferation of existing cells or tissue stem cells to restore damaged tissues
48
Define organisation
Replacement of damaged tissues by granulation tissue as part of the process of tissue repair
49
Define scare formation (connective tissue deposition, CTD)
Form of tissue repair occurring in tissues unable to regenerate or too severely damaged (damage to ECM) to adequately support regeneration. Scar formation involves the process of organisation.
50
Define fibrosis
The deposition of excessive collagen in certain organs in response to chronic inflammation or tissue necrosis (but this term is often used interchangeably with scarring/scar formation )
51
What are the two purposes of tissue response
Contain damage
Start healing/repair
52
define tissue repair
The restoration of tissue architecture/function following injury, essential for survival
53
When does regeneration occur over scar formation
When does scar formation occur
When there’s mild superficial injury and the tissue has the ability to repair itself through existing cells/stem cells that can divide
Severe injury or no cells to divide
54
The process of regeneration results in what
Resolution
55
The ability of a tissue to regenerate depends on what 3 things
a) Intrinsic proliferative capacity of the cells in the tissue (i.e. can they divide)
b) The presence of stem cells (i.e. can the stem cells replace lost cells)
c) Integrity of supporting connective tissue framework (i.e. is the connective tissue support intact)
56
What does scar formation result from
Severe tissue damage
Damage to parenchyma/connective tissues/ stem cells
Cannot regenerate
Deposition of collagen
Fibro-proliferation response patches up tissues
57
Define scar
The end result of replacement of any tissue parenchyma by collagen
58
List the steps in scar tissue formation
1. Inflammation
* Acute & chronic inflammatory cells (inc. macrophages)
2. Cellular proliferation
* Epithelial -> repair surfaces at injury site
* Endothelial cells / pericytes -> "angiogenesis"
* Fibroblasts - deposition of collagen
3. Granulation tissue formation (organisation)
4. Deposition of connective tissue
5. Wound contraction (sometimes)
* Inflammation
- Removes / contains harmful agent
* Blood vessel proliferation (angiogenesis)
- Release of angiogenic factors (VEGFs) -> stimulates blood vessel growth
- Promotes † delivery of cells / substances to injured area
- New vessels leaky - release of plasma proteins
Activated macrophages
* Fibroblast proliferation (mainly via M2 macrophages)
. BV / fibroblast proliferation + GRANULATION TISSUE (ORGANISATION)
* Infiltrates damaged area
"Loose" connective tissue laid down
* Cellular migration
- TGFß in granulation tissue ->
- Fibroblast migration / proliferation
Macrophage
Deposition of connective tissue
- TGFß -> fibroblasts -> collagen
- Inflammation, edema and blood vessels regress
- Scar formed by collagen, fibroblasts
* Wound contraction (if applicable)
- If large surface (skin / mucosal) wounds - helps reduce wound sizes
Fibroblasts -> myofibroblasts (smooth muscle like) - contract
59
What does granulation tissue look like
Has a granular appearance
60
What is the difference between primary (small, thin wound) and secondary intention (large, thicker )cutaneous wound healing
- volume of clot results in greater inflammatory response
- more abundant granulation tissue in 2nd
- wound contraction by myofibroblasts
61
Pathology of healing/repair
* Inadequate granulation tissue formation
- Wound dehiscence
- Ulceration
* Excessive granulation tissue
* Excessive formation of repair tissues
- Hypertrophic scars
- Keloid
* Contractures
Esp. burns
62
Difference between acute and chronic in terms of
- cardinal signs
- duration
- outcomes
- inflammatory cells
- vascular changes
- fluid exudation
- healing by fibrosis
Acute
- yes
- hours/days
- resolution, regeneration, some fibrosis
-neutrophils
- increased permeability
- yes
- no
Chronic
- no
- weeks/months
-fibrosis, tissue replacement, scar
- lymphocytes, plasma cells, macrophages
- proliferation
- no
- yes
63
What type of macrophages are involved in tissue repair and fibrosis
M2
64
When is the term fibrosis used
When the care tissue is excessive or prominent but the mechanisms are the same
Excessive deposition of collagen in chronic disease
65
Various cells in injured tissues produce what
Growth factors including macrophages
66
Tissue repair occurs by what two processes
Regeneration
Scar formation (CTD)
