Trans 4 - Inflammation and Repair Flashcards
-Response of living, vascularized tissue to injury
-Role is to destroy or isolate injurious agents in order to
achieve healing and repair
inflammation
The pattern of inflammation is determined by
- Inciting agent
- Time of observation
- Immune status of host
The inciting agents of inflammation are
- Infection
- Trauma
- Physical and chemical agents
- Tissue necrosis
- Foreign bodies
- Immune reactions
What kind of inflammation has an early onset (seconds to minutes) and short duration (minutes to days)
acute inflammation
acute inflammation involves
- fluid exudation (edema)
- plasma proteins
- polymorphonuclear cell (neutrophil) emigration
Inflammation that has
-later onset (days)
-longer duration (weeks to years)
-Characterized by tissue infiltration with
macrophages, lymphocyte, and plasma cells, or
eosinophil – all derived from blood.
chronic inflammation
Chronic inflammation induces
blood vessel proliferation and scarring
acute inflammation is characterized by
- Changes in blood flow
- Increased vascular permeability
- Infiltration of tissues by neutrophils
Acute inflammation may lead to:
- Complete resolution
- Healing by connective tissue replacement (scarring)
- Chronic inflammation
cardinal signs of inflamation
dolor, rubor, calor, functio laesa, tumor
Rubor means
redness
causes of rubor and calor
vessel dilatation and
increased blood flow to the
inflamed part
calor means
warmth
dolor means
pain
causes of dolor
Increased pressure on nerve endings from swelling, and a direct effect of certain chemical factors which are released to mediate response
tumor means
swelling
causes of tumor
Accumulation of fluid especially exudates
functio laesa means
loss of function
causes of functio laesa
When swelling and pain are marked, there is partial or
complete loss of function of the inflamed structure.
what are the components of acute inflammation
vascular changes, cellular events,
Alterations in vascular caliber that lead to an
increased blood flow
vasodilation
Structural changes in the microvasculature that
permits plasma proteins and leukocytes to leave the
circulation
hallmark of acute inflammation: increase in vascular permeability
changes in blood flow
-Transient arteriolar constriction results in shortlived
decreased blood flow to the area.
-Followed by dilatation of arterioles and opening of
capillary beds resulting in increased blood flow
(causing rubor and calor)
-Slowing of blood (stasis) leading to leukocyte
margination (sticking of cells to the vessel wall)
Structural changes in the microvasculature that permit
leakage of plasma proteins and leukocytes into the
damaged area
increased vascular permeability
causes of increased vascular permeability
- Formation of gaps due to endothelial contraction
- Endothelial injury
- Leukocyte-mediated endothelial injury
- Increased Transcytosis
-Occurs in arterioles, capillaries, venules
-Caused by burns, some microbial toxins, and
chemicals
-Rapid: may be long-lived (hours to days
endothelial injury
- Occurs in venules, pulmonary capillaries
- Associated with late stages of inflammation
- Long-lived
leukocyte-mediated endothelial injury
- Occurs in venules even if there are no gaps produced
- Induced by vascular endothelial growth factor (VEGF)
- Caused by increased transit of vesicles and vacuoles across
Increased Transcytosis
A critical function of inflammation is the delivery of
______________ to the site of injury.
leukocytes
Slowing of blood flow promotes ___________ and ___________ of leukocytes to swollen endothelial cells.
margination and
adhesion
transmigration aka
diapedesis
the migration in interstitial tissues toward a chemical stimulus/chemotaxin along a chemical gradient.
chemotaxis
Involves interactions between complementary
adhesion molecules on leukocytes and
endothelium, modulated by chemical mediators
leukocyte adhesion
Leukocytes pierce the basement membrane by
secreting
collagenases
Steps in leukocyte migration
rolling, firm/stable adhesion, transmigration
Directed migration of leukocytes towards chemical
stimulus; exogenous and endogenous substances
act as chemoattractants
chemotaxis
chemotactic agents include
- Leukotriene B4
- Platelet Activating Factor
- C5a
- IL-8
- Bacteria-derived N-formyl peptides
Recognition and attachment of the particle to be
ingested; responsible for the elimination of injurious
agent
phagocytosis
two major opsonins
- Fc fragment of IgG
- C3b
involves CR3 which recognized C3bi
non-opsonic phagocytosis
Steps in Bacterial Killing by Phagocytosis
recognition, engulfment, fusion, degradation
oxygen-independent mechanism includes
- Bacterial Permeability Protein (BPIP)
- Lysozyme
- Lactoferrin
- Major Basic Protein
- Arginine-rich defensins
Myeloperoxidase deficiency leads to
chronic granulomatous disease
Shows thin (virtually invisible) blood vessels in the alveolar walls and no cells in the alveoli.
normal lung
- Fluid is the major component
- Derived from either the blood serum or the secretions of mesothelial cells lining the peritoneal, pleural, or pericardial cavities.
- Pleural tuberculous effusion
serous inflammation
-Fibrin is abundant
-Often seen in relation to serosal surfaces of body cavities such as pericardium or pleura
-Occurs in more severe injuries and greater vascular permeability (fibrinogen passes the vascular barrier)
-Resolution or scarring 9-inch growth of fibroblasts and
blood vessels.
fibrinous inflammation
-Neutrophils dominate the composition
-Production of large amounts of pus or purulent
exudates consisting of neutrophils, necrotic cells, and
edema fluid
-Material is liquefied to form pus
-Pyogenic (pus-producing) staphylococcal abscesses
Suppurative or Purulent Inflammation
-Local defect, or excavation, of the surface or an organ
or tissue.
-Produced by the sloughing (shedding) of inflammatory
necrotic tissue (mucosa is totally sloughed off and
submucosa is affected
-Acute and chronic inflammation exist
ulcer
balance between continued tissue damage and repair
chronic inflammation
prolonged process (weeks or months) in which active inflammation, tissue destruction and healing all proceed simultaneously
chronic inflammation
Histologically, chronic inflammation shows the following typical features that differentiate it from acute inflammation:
-Infiltration with mononuclear cells, which include
macrophages, lymphocytes, and plasma cells, a reflection of persistent reaction to injury
-Tissue destruction, largely induced by the inflammatory
cells.
-Attempts at repair by connective tissue replacement,
namely proliferation of small blood vessels (angiogenesis), and in particular, fibrosis.
-If the damaging stimulus is eradicated, there is NO
further tissue necrosis
-Repair response progresses to complete scarring
healing
-If the damaging stimulus CANNOT be eradicated
-Balance between damage and repair may be in a
stalemate and may persist for years
-If repair process is overwhelmed and damaging
stimulus progresses
-Ulceration may continue leading to perforation
chronicity
Induced by parasites or allergic reactions
eosinophilic responses
Found in hypersensivity reactions, viral infections ,
and neoplasms
Lymphocytic and plasma responses
Often mixed with other acute or chronic inflammatory
cells
macrophage responses
-Collection of activated macrophages that may
coalesce to form multinucleate giant cells
-Often surrounded by a collar of lymphocytes
and fibroblasts.
granuloma
-Characterized by the presence of granulomas,
which are indicative of certain diseases
-Mediated by lymphokines from activated T-cells
Granulomatous response
- Primary mediator of granulomatous inflammation
- Facilitates activated macrophages
Interferon-γ (IFN- γ) and Interleukin-4 (IL-4)
What type of granulomatous inflammation is this
-Aka immune granuloma
-If T cell-mediated immunity is impaired, there will be small disseminated granulomas (miliary TB, lepromatous
leprosy, HIV)
-Some have no identifiable antigens (e.g.,
sarcoidosis)
Hypersensitivity Type
What type of granulomatous inflammation is this
- Aka foreign-body granuloma
- Response to poorly digestible materials
- Incited by relatively inert foreign bodies
Non-hypersensitivity Type
A regulated physiologic reaction associated with
inflammatory conditions, and is mediated by cytokines
released during the inflammatory process.
acute phase response
It is clinically characterized by fever, leukocytosis,
decreased appetite, altered sleep patterns, and changes
in plasma levels of acute phase proteins.
acute phase response
Fever is mediated by the effects of ___, ___, and ___ on
hypothalamus either directly (TNF), or indirectly by local PGE2 synthesis
TNF, IL-1, and IL-6
Leukocytosis is mediated by ___ and ____
IL-1 and TNF
-Occurs initially due to accelerated release of
bone marrow cells
-Prolonged infection also induces proliferation of
precursors in the bone marrow, induced by
colony-stimulating factors.
leukocytosis
type of infection: bacteria
associated response:
Neutrophilia
type of infection: viral
associated response:
Lymphocytosis
type of infection: Parasitic and allergic
associated response:
Eosinophilia
plasma proteins is regulated by ___ and ___
IL-6 and IL-1
Synthesis and plasma levels increase in acute phase response
Acute-phase proteins
downregulate inflammation
a1-antitrypsin, cystein proteinase inhibitor, ceruloplasmin)
Synthesis and plasma levels decrease in acute phase response
Negative acute-phase proteins
Replacement of lost cells or tissue by elements of
identical structure and function
regeneration
Replacement by connective tissue resulting in fibrosis
scarring
-Seen in acute or mild injury
-Occurs when parenchymal cells have high proliferative
capacity
-ECM framework is preserved
regeneration
-Seen in chronic or massive injury
-Occurs when parenchymal cells have low proliferative
capacity
-ECM framework is destroyed
scarring
Replacement of injured tissue by connective tissue
resulting in fibrosis and scarring (when regeneration
cannot be accomplished)
repair
Repair begins while inflammation is still present, but is completed after inflammation terminates
Inflammation and repair coexist during the first week
of injury
new blood vessel formation
neovascularization
fibrous tissue deposition
fibrosis
Promote chemotaxis and proliferation of endothelium
FGF (Fibroblast growth factor)
Vascular permeability factor (VPF)/Vascular
endothelial growth factor (VEGF)
Can mediate all the steps in angiogenesis
FGF (Fibroblast growth factor)
Causes both angiogenesis and increased vascular permeability
Vascular permeability factor (VPF)/Vascular endothelial growth factor (VEGF)
Promote migration and proliferation of fibroblasts and
myofibroblasts
- IL-1 and TNF-a
- Transforming growth factor-β (TGF-β)
- Fibroblast growth factor (FGF)
- Platelet-derived growth factor (PDGF)
Promote extracellular matrix (ECM) deposition
- IL-1
- Transforming growth factor-β (TGF-β)
- Fibroblast growth factor (FGF)
- Platelet-derived growth factor (PDGF)
Monocyte chemotaxis
Chemokines, TNF, PDGF, FGF, TGF- β
Fibroblast migration/replicaton
PDGF, EGF, FGF, TGF- β, TNF, IL-1
Keratinocyte replication
HB-EGF, FGF-7, HGF
Angiogenesis
VEGF, angiopoietins, FGF
Collagen synthesis
TGF- β, PDGF
Collagenase secretion
PDGF, FGF, TNF, TGF-β inhibits
-Removal of inflammatory exudates and debris by
macrophages
-Fibrin clot and cross-linking of plasma protein with ECM
components
-Chemotactic and mitogenic factors released by
macrophages promote angiogenesis
Inflammatory Phase
inflammatory phase starts
after formation of the inflammatory exudates
- Development of vascular granulation tissue
- Development of fibrovascular granulation tissue
- Development of ECM in granulation tissue
proliferative phase
-Grows into injured area from surrounding healthy
tissue
-Consists of newly formed capillaries, proliferating
fibroblasts, and residual inflammatory cells
Development of vascular granulation tissue
-Tissue defect is filled with a complex capillary
network, proliferating fibroblasts and myofibroblasts,
and a few residual macrophages
-There is now active collagen synthesis
Development of fibrovascular granulation tissue
-Initially ECM rich in fibronectin and proteoglycans (a
loose network to hold fibrin)
-Fibronectin mediates adhesion of growing capillaries
and fibroblasts and enhances response to FGF
-Type III collagen appears after one week
-Type I collagen begins to appear after two weeks
Development of ECM in granulation tissue
Proliferative phase is controlled by
cytokines and growth factors derived from macrophages, lymphocytes, and platelets
-Maturation and reorganization of fibrous tissue
-Type III collagen secreted early is later degraded and
replaced by Type I collagen
Maturation Phase
As part of the increase in the strength of a wound, the
secreted collagen undergoes maturation to become
scar tissue
In would healing, what are seen in 24 hours
neutrophils
-Mass composed of protuberant accumulation of -
connective extending beyond initial wound
-Similar to hypertrophic scar, which does not
extend beyond initial wound
keloid
-Proliferation of fibroblasts and other repair
elements
-Interface between benign and low-grade
malignant tumors
Desmoids or aggressive fibromatoses
