LEC5 - INFLAMMATION Flashcards
The word inflammation from the Latin
inflammare
(to set on fire)
according to him, inflammation is not a disease but only a protective response
john Hunter, Scottish surgeon in 1793:
Inflammation is a protective response involving:
- host cells
- blood vessels
- proteins and
- other mediators
host cell are involved if the inflammation is ?
acute or chronic
A response of vascularized tissues to infections and damaged tissues that brings cells and molecules of host
defense from the circulation to the sites where they are needed, in order to eliminate the offending agents
inflammation
The word inflammation from the Latin
inflammare (to set on
fire)
he profound the 4 signs of inflammation - cardinal signs
o Rubor – redness
o Tumor – swelling
o Calor – heat
o Dolor – pain
*These signs are hallmarks of acute inflammation
o Rubor – redness
o Tumor – swelling
o Calor – heat
o Dolor – pain
he Added the 5th sign “Functio leasa” of inflammation
Rudolf Virchow (19th century)
he says that Inflammation is not a disease but a stereotypic response
that has salutary effect on its host
John Hunter (1793)
she Discovered the process of phagocytosis
Elie Metchnikoff (1880s)
in order to clear up or eliminate the initial cause of inflammation is through the process of
phagocytosis
2 etiology of inflammation
exogenous and endogenous
exogenous causes of inflammation
physical agents
chemical agents
biological agents
endogenous causes of inflammation
circulation disorders
enzyme activation
metabolic products deposals
Physical agents of inflammation
o Mechanic agents:
o Thermal agents:
under the physical agents, give example of mechanical agents
fractures, foreign, sand
under the physical agents, give example of thermal agents
burns or freezing
example of chemical agents
toxic gases, acids, bases
example of biological agents
microorganism
an endogenous causes, give example of circulation disorders
thrombosis, infarction, hemorrhage
an endogenous causes, give example of enzyme activation
acute pancreatitis
an endogenous causes, give example of metabolic deposals
uric acid, urea, cholesterol
all intracellular accumulation will fall in what category of exogenous causes of inflammation??
metabolic product deposals
CHANGES IN INFLAMMATION
- Tissue damage
- Cellular – vascular response
- Metabolic changes (external manifestation)
- Tissue repair
in acute inflammation, what are the cellular infiltrate
neutrophils
in chronic inflammation, what are the cellular infiltrate
Monocytes/macrophages
and lymphocytes
ACUTE
Tissue injury,
fibrosis
Usually
mild &
self-limited
CHRONIC
Tissue
injury,
fibrosis
Often severe and
progressive
ACUTE
Local &
systemic
signs
Prominent
CHRONIC
Local &
systemic
signs
Less prominent;
may be subtle
ACUTE INFLAMMATION
It is characterized by
o Exudation of fluids and plasma proteins (edema fluid)
o Emigration of neutrophilic leukocytes to the site of
injury
a type of inflammation that is An immediate and early response to an injurious agent
ACUTE INFLAMMATION
the cardinal sign is also called as
the external manifestation of acute inflammation
cardinal sign
Due to dilation of small blood vessels within
damaged tissue (cellulitis)
REDNESS
(RUBOR)
cardinal sign
Results from increased blood flow (hyperemia)
due to regional vascular dilation
HEAT (CALOR)
cardinal sign
Due to the accumulation of fluid in the
extravascular space.
SWELLING
(TUMOR)
CARDINAL SIGNs
Results from the stretching & destruction of
tissues due to inflammatory edema
PAIN (DOLOR)
CARDINAL SIGNS OF ACUTE INFLAMMATION
inflamed area is inhibited by pain
Severe swelling may physically immobilize the
tissue
LOSS OF
FUNCTION
Chemicals of acute inflammation (mediators)
Bradykinins
Prostaglandins
Serotonin
Chemicals of acute inflammation (mediators)
function of bradykinins
contribute for blood vessel dilation
Chemicals of acute inflammation (mediators)
function of prostaglandin
vascular and systemic reaction
Chemicals of acute inflammation (mediators)
function of serotonin
happy hormones
EVENTS OF ACUTE INFLAMMATION
VASCULAR CHANGES
CELLULAR EVENTS
VASCULAR CHANGES in acute inflammation
- Increase in blood flow (vasodilation)
- To bring cells and proteins to
the site of injury - By vasodilation and increased
vascular permeability
(vascular leakage) by the
chemical mediators especially
histamine
CELLULAR EVENTS of acute inflammation
- Recruitment of leukocytes
- Activation of leukocytes
leading to the process
of destruction of
invaders and production
of mediators
Stages of Vascular response
(1) Vascular dilation and
increased blood flow
(2) extravasation and deposition
of plasma fluid and proteins
(edema)
(3) leukocyte (mainly
neutrophil) emigration and
accumulation in the site of injury.
the vascular dilation and increased blood flow will cause
causing erythema and
warmth
Mechanism of Vascular response
Vasoconstriction
vasodilation of arterioles and venules
stasis of blood flow
oozes protein-rich fluid into
extravascular tissues.
exudates clinically appears as
swelling. (edema)
Stages of Margination
Rolling
Pavementing
is a peripheral positioning of white cells along the endothelial
cells.
Margination
rows of leukocytes tumble slowly along the
endothelium
Rolling
endothelium can be lined by white cells the binding of leukocytes with endothelial cells is facilitated by cell
adhesion molecules
Pavementing
Transmigration of
leukocytes through the process of
Diapedesis
The movement of leukocytes
by extending pseudopodia
through the vascular wall.
Diapedesis
Stages of cellular
response
Margination
Transmigration
chemotaxis
phagocytosis
- unidirectional attraction of leukocytes from vascular channels
towards the site of inflammation within the tissue space
guided by chemical gradients.
Chemotaxis
The important chemotactic factors for neutrophils
(C5a)
* leukotriene B4
*cytokines (IL-8)
(C5a) is composed of
complement system, bacteria and mitochondrial products of
arachidonic acid metabolism:
is the process of engulfment and
internalization by specialized cells of particulate material.
Phagocytosis
Phagocytic cells
- polymorphonuclear leukocytes (neutrophiles),
*monocytes - tissue macrophages.
Leukocyte recruitment is a multi-step process consistin
§ loose attachment to and rolling on endothelium (mediated by selectins);
§ firm attachment to endothelium (mediated by integrins)
§ migration through interendothelial spaces
Steps of the inflammatory response (5Rs)
- Recognition of the injurious agent - etiology of the inflammation
- Recruitment of leukocytes
- Removal of the agent
- Regulation (control) of the response
- Resolution (repair
Defects in Leukocyte Function can be either ___ and ___
acquired and inherited
lead to increased susceptibility to infections, which may be recurrent
and life-threatening
Defects in Leukocyte Function
acquired disease in defect of leukocyte function
bone marrow suppresion
radiation, chemo therapy
diabetes, malignancy, sepsos, chronic dialysis
genetic causes of leukocyte disorder
leukocyte adhesion deficiency 1
leukocyte adhesion deficiency 2
chronic granulomatous disease
x linked
autosomal recessive
myeloperoxidase deficiency
chediak-higashi syndrome
defect in bone marrow suppression, tumor, radiation and chemotheraphy
production of leukocytes
defect in leukocyte function in diabets, maklignancym sepsis and chronic dialysis
adhesion and chemotaxis
defect in leukocyte for anemia, sepsis, diabetes, and malnutrition
phagocytosis and microbicidal activity
defect in leukocyte function wherein there’s defect in adhesion because of the mutations in B chain of CD 11/ CD18 integrins
leukocyte adhesion deficiency 1
a defect in leukocyte function wherein there’s a decreased oxidative burst
chronic granulomatous disease
defect in leukocyte function wherein there’s defect in adhesion because of the mutations in fucosyl transferase required for synthesis of sialated ologosaccharide (receptor for selectisn)
leukocyte adhesion deficiency 2
a defect in leukocyte function wherein there’s a phagocyte oxidase (membrane component)
x linked
a defect in leukocyte function wherein there’s a phagocyte oxidase (cytoplasmic components )
autosomal recessive
a defect in leukocyte function wherein there’s a decreased in microbial killing because of defective MPO-H2O2 system
myeloperoxidase deficiency
a defect in leukocyte function wherein there’s a decreased leukocyte function because of the mutations affecting protein involved in lysosomal embrane traffic
chediak-higashi syndrome
Three steps in Phagocytosis
(1) recognition and attachment of the
particle to the ingesting leukocyte
(2) engulfment, with subsequent
formation of a phagocytic vacuole
(3) killing and degradation of the
ingested material
The outcome of acute inflammation
*Elimination of the noxious stimulus
*Decline of the reaction
* Repair of the damaged tissue,
* Persistent injury resulting in chronic inflammation.
Persistent injury resulting in
chronic inflammation.
Outcomes of acute
inflammation:
resolution,
healing by scarring (fibrosis),
chronic inflammation
example of causes of acute inflammation
infarction
bacterial infection
toxins
trauma
according to the diagram what are the characteristic or component of acute inflammation
vascular changes
neutrophil recruitment
mediators
according to the diagram what are the characteristic or component of chronic inflammation
angiogenesis
mononuclear cell infiltrate
fibrosis (scar)
healing in acute inflammation will result to
clearance of injurious stimuli
clearance of mediators and acute inflammatory cells
replacement of injured cells
normal function
if an acute inflammation result to pus formation or abscess, it will then heal as a ___
fibrosis
healing in chronic inflammation will result to
fibrosis - loss of function
Morphological Feature of AI
*Serous inflammation
*Fibrinous inflammation
*Suppurative (purulent) inflammation
is characterized by the outpouring of a watery, relatively
protein-poor fluid that, depending on the site of injury,
*Serous inflammation
*Fluid in a serous cavity is called an
effusion
resulting in greater vascular permeability allows large molecules such as fibrinogen to pass the endothelial barrier
fibrinous inflammation
a ____ is a characteristic of inflammation in the lining of body cavities
fibrinous exudate
a fibrinous exudate came from the lining of body cavities such as
meninges, pericardium, pleura
manifested by the presence of large amounts of purulent exudate (pus)
*Suppurative (purulent) inflammation
*Suppurative (purulent) inflammation consist of what cells
onsisting of neutrophils, necrotic cells, and edema fluid.
* (e.g., staphylococci)
are focal collections of pus that may be caused by seeding of
pyogenic organisms into a tissue
abscesses
secondary infections of necrotic foci
Abscesses
is a local defect, or excavation, of the surface of an organ or tissue
that is produced by necrosis of cells and sloughing (shedding) of
inflammatory necrotic tissue
ulcer
highest immigration of cells
abscess
cell derived mediators
histamine
serotonin
prostaglandins
leukotrienes
platelet-activating factor
reactive oxygen species
nitric oxide
cytokines
neuropeptides
a cell derived preformed mediators in secretary granules
histamine
serotonin
source of histamine
mast cells, basophilic, platelets
source of serotonin
platelets
mediators in vasodilation
prostaglandins
nitric oxide
histamine
mediators for increased vascular prmeabilty
histamine and serotonin
bradykinin
c3a and c5a
leukotrienes
PAF
susbtance P
is inflammation of prolonged duration
chronic inflammation
in which active inflammation, tissue injury, and healing proceed
simultaneously.
Chronic inflammation
chronic inflammation is characterized by:
◦ Infiltration with mononuclear cells
◦ macrophages,
◦ lymphocytes,
◦ plasma cells
◦ Tissue destruction,
◦ Repair, involving new vessel proliferation (angiogenesis) and fibrosis
the dominant cells of chronic inflammation
Macrophages
lungs macrophage is called as
alveolar macrophage
central nervous system macrophage
(microglial cells),
- spleen and lymph nodes macrophage
( sinus histiocytes),
a chronic inflammatory cell that develops from activated b lymphocyes and produces antbodies
plasma cells
a chronic inflammatory cells that are characteristically found in inflammatory sites around parasitic infections or as part of immune reactions
eosinophil
what Ig is eosinophil associated with
IgE
a chronic inflammatory cells that is distributed in connective tissues throughout the body, and they can participate in both acute and chronic inflammatory responses
mast cells
This involves a diffuse
accumulation of
macrophages and
lymphocytes at site of
injury that is usually
productive with new
fibrous tissue
formations
Nonspecific chronic
inflammation:
Classification of chronic inflammation
Nonspecific chronic
inflammation:
specific chronic inflammation (granulomatous inflammation)
characterized by the presence of
granuloma.
Specific inflammation
(granulomatous inflammation):
is a microscopic aggregate of
epithelioid cells.
granuloma
cell is an activated
macrophage, with a modified
epithelial cell-like appearance.
The epitheloid cells can fuse
with each other & form
multinucleated giant cells.
Epithelioid
The ___ can fuse
with each other & form
multinucleated giant cells.
epithelioid cells
is a distinctive pattern of chronic
inflammation characterized by
aggregates of activated
macrophages that assume an
epithelioid appearance
*Granulomatous inflammation
a typucal granuloma resulting from infection with mycobacterium tuberculosis showing central caseous necrosis
granulomatous inflammation
Two types of giant cells
Foreign body-type giant cell
Langhans giant cells
a type of giant cell which have irregularly scattered nuclei in
presence of indigestible materials.
Foreign body-type giant cells
a type of giant cell in which the nuclei are arranged peripherally in a horse shoe patter which is seen typically in tuberculosis and sarcoidosis
Langhans giant cells
Types of granulomas
Foreign body granuloma
Immune granulomas
granulomas are initiated by inert fore
Foreign body granuloma
*Antigen presenting cells (macrophages)
engulf a poorly soluble inciting agent.
Immune granulomas
*Macrophage inhibitory factor helps to
localize activated macrophages and
epitheloid cells
Immune granuloma
Major causes of
granulomatious inflammation
Bacterial
fungal
helminthic
protozoal
chlamydia
Bacterial cause of granulomatous inflammation
Tuberculosis, Leprosy, Syphilis, Cat scratch
disease, Yersiniosis
fungal cause of granulomatous inflammation
Histoplasmosis, Cryptococcosis,
Coccidioidomycosis, Blastomycosis
helminthic cause of granulomatous inflammation
Schistosomiasis
protozoal case of granulomatous inflammation
Leishmaniasis, Toxoplasmosis
chlamydia case of granulomatous inflammation
Lymphogranuloma venerum
SYSTEMIC EFFECTS OF
INFLAMMATIONS
*a. Fever
*b. Endocrine & metabolic responses
*c. Autonomic responses
*d. Behavioral responses
*e. Leukocytosis
* f. Leukopenia
*g. Weight loss
restoration of tissue architecture and function
after an injury
Tissue repair
Tissue Repair occurs in
– Regeneration of injured tissue
– Replacement by connective tissue (scarring) - Usually, tissue repair involves both processes
Tissue Repair involves
- cell proliferation-
interaction between cells and extracellular matrix
Mechanisms regulating cell
populations
Cell numbers can be altered by:
§ increased or decreased rates
of stem cell input
§ cell death due to apoptosis
Changes in the rates of
proliferation or differentiation
Processes in the proliferation of cells
- DNA replication
2.Mitosis
Cellular Proliferation
divided into three groups
*. Continuously dividing (labile) tissues
** Stable tissues
** Permanent tissues
mechanism of labile tisues
** Cells are continuously proliferating
** Can easily regenerate after injury
** Contain a pool of stem cells
example of Continuously dividing (labile) tissues
bone marrow, skin, epithelium
*Cells have limited ability to proliferate
*Limited ability to regenerate
*Can proliferate if injured
Stable tissues
Stable tissues examples
Examples: liver, kidney, pancreas
Cells can’t proliferate
*Can’t regenerate
* injury always leads to scar
Permanent tissues
Permanent tissues examples
: neurons, cardiac muscle
Three phases in granulation -
tissue
Phase of inflammation
Phase of demolition
ingrowth of granulation tissue
3 phases of granulation
inflammatory exudate, platelet aggregation and fibrin
deposition.
what happen in phase of demolition
*The dead cells liberate their autolytic enzymes.
*There is an associated macrophage infiltration.
what happen in Ingrowth of granulation tissue
proliferation of fibroblasts and an ingrowth of new blood
vessels into the area of injury, with a variable number of
inflammatory cells.
is a mechanical
reduction in the size of the defect
Wound contraction
esults in much faster healing,
*If ___________ is prevented, healing is slow
and a large scar is formed.
contraction
have the capacity to stimulate cell division and
proliferation
Growth factors
Sources of Growth Factors:
- Platelets, activated (TGF)
*2. Damaged epithelial cells, (EGF)
*3. Circulating serum growth factors,
*4. Macrophages, (angiogenic factor)
*5. Lymphocytes recruited to the area of injuryowth Factors:
The main phases of cutaneous wound
healing:
*Inflammation
*Formation of granulation tissue
*ECM remodeling
*___ is the network that surrounds cells
ECM
- Two forms of ECM
interstitial matrix and basement membrane
interstitial matrix componnt
fibrillar collagen
elastin
proteoglycan and hyaluronan
It provides mechanical support to tissues
ecm
- It acts as a substrate for cell growth and the formation of
tissue microenvironments.
ECM
It regulates cell proliferation and differentiation
ecm
_____ stimulate cells through cellular integrin
receptors.
fibronectin and laminin
__bind growth factors and display them at high
concentration, and
proteoglycans
An intact ECM is required for tissue regeneration
true or false
true
healing of the epidermis
regeneration
(healing of the dermis
repair by scarring
Two patterns of healing
. Healing by first intention
Healing by second intention
Occurs in small wounds that close
easily
healing by first intention
Healing by first intention
(primary union)
_____ predominates
over fibrosis
epithelial regeneration
healing by first intention
By 24 hours
- clot forms
- neutrophils come in
- epithelium begins to regenerate
healing by first intention
By 3-5 hours
- macrophages come in
- granulation tissue is formed
- new blood vessels
- fibroblasts
- collagen begins to bridge incision
- epithelium increases in thickness
healing by first intention
By weeks later
- granulation tissue gone
- collagen is remodeled
- epidermis full, mature
- eventually, scar forms
larger wounds that have gaps between wound margins
Healing by second intention
(secondary union)
Fibrosis predominates over epithelial regeneration
healing by second intentoin
Healing is slower, with more inflammation and
*granulation tissue formation, and more scarring
Healing by second intention
(secondary union)
*Local Factors
*> Type, size, and location of the wound
* > Vascular supply
* > Infection
* > Movement
* > Ionizing radiation
Systemic Factors
circulatory statius
infection
metabolic status
Nutritional deficiencies
Complications of Wound Healing
infection
deficient scar formation
excessive scar formation
Excessive Scar Formation will form
Keloid Formation
Hypertrophic Scar
Deficient Scar Formation will lead to
Wound Dehiscence
Ulceration
