inflammation and tissue healing and repair Flashcards
Inflammation is a protective response involving
- host cells
- blood vessels
- proteins and
- other mediatiator
mission of inflammation
to eliminate the initial cause of cell injury
inflammation protective mission by
- Diluting
- destroying
- Neutralizing
what is inflammare
to set on fire
rubor et tumor cum calore et dolore
redness and swelling with heat and pain
who added the 5th sign
Rudolf virchow
what is the 5th cardinal sign
functio laesa or loss of function
who said inflammation is not a disease but just a response
John Hunter
Who discovered the process of phagocytosis
Elie Metchinkoff
Exogenous causes
Physical agents
Chemical agents
Biological agents
Endogenous causes
Circulation disorders
Enzymes activation
Metabolic products deposals
Target of cell injury
- function
- biochemical reaction
Changes in inflammation
- Tissue damage
- Cellular –vascular response
- Metabolic changes
- Tissue repair
onset of acute
onset of chronic
fast: mins or hours
slow: days
tissue injury of acute
tissue injury of chronic
acute - mild and self-limited
chronic - severe and progressive
why is it prominent in acute inflammatory?
because the 5 cardinal signs are seen in acute inflammation,
an immediate and early response to an injurious agent
acute inflammation
characteristics of AI
- presence of exudates fluids and plasma proteins
- emigration of neutrophilic leukocytes to the site of injury
external manifestation of AI
- rubor
- calor
- tumor
- dolor
due to dilation of small blood
vessels within damaged tissue
rubor or redness
example of rubor
cellulitis
results from increased blood flow due to regional vascular dilation
calor or heat
example of calor
hyperemia
due to accumulation of fluid in the
extravascular space
tumor or swelling.
results from the stretching & destruction of tissues due to inflammatory edema
dolor or pain
inflamed area is inhibited by pain
loss of function
chemicals or mediator of AI that contributes to vasodilation
- bradykinins
- prostaglandins
- serotonin
2 events of AI
- vascular response / vascular changes
- cellular response / cellular changes
what are the vascular response/vascular changes?
- there will be increase in the blood flow
- to bring cells and proteins to the site of injury
- by vasodilation and increased vascular permeability
what are the cellular response/cellular changes?
- recruitment of leukocytes
- activation of leukocytes leading to the process of destruction of invaders and production of mediators
Stages of Vascular response
- Vascular dilation and increased blood flow
- extravasation and deposition
of plasma fluid and proteins - leukocyte emigration and
accumulation in the site of injury
Mechanism of vascular response
- Vasoconstriction
- Vasodilatation of arterioles and
venules - Stasis of blood blood flow
immediate due to neurogenic/ chemical stimuli
vasoconstriction
Stages/mechanism of cellular
response
- margination
- diapedesis
- chemotaxis
- phagocytosis
peripheral positioning of white cells along the endothelialcells
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
mediator of margination
- selectins
- immunoglobulins
- integrins
The movement of leukocytes
by extending pseudopodia
through the vascular wall
diapedesis
unidirectional attraction of leukocytes from vascular channels
towards the site of inflammation within the tissue space
guided by chemical gradients.
chemotaxis
important chemotactic factors for neutrophils
- C5a complement system
- leukotriene B4
- cytokines (IL-8)
the process of engulfment and
internalization by specialized cells of particulate material
phagocytosis
Leukocyte recruitment is a multi-step process consisting of
- 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
- Recruitment of leukocytes
- Removal of the agent
- Regulation (control) of the response
- Resolution (repair)
Defects in Leukocyte Function
could be acquired or inherited
Defects in Leukocyte Function
lead to increased susceptibility to infections, which may be recurrent
and life-threatening
Acquired diseases
- diabetes
- sepsis
- anemia
- malignancy
- malnutrition
Genetic diseases
- chronic granulomatous
- X-linked
- autosomal recessive
Major role of P-selectin
rolling
major role of e-selectin
rolling and adhesion
three steps in Phagocytosis
- recognition and attachment of the
particle to the ingesting leukocyte - engulfment, with subsequent
formation of a phagocytic vacuole - 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
Outcomes of acute
inflammation:
- Resolution
- Fibrosis or healing by scarring
- chronic inflammation
Morphological Feature of AI
- Serous inflammation
- Fibrinous inflammation
- Suppurative (purulent) inflammation
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
effusion
resulting in greater vascular permeability allows large molecules to pass the endothelial barrier
fibrinous inflammation
fibrinous exudate is characteristics of inflammation in the lining of body cavities
meninges
pericardium
pleura
manifested by the presence of large amounts of purulent exudate
Suppurative (purulent) inflammation
focal collections of pus that may be caused by seeding of
pyogenic organisms into a tissue
Abscesses
secondary infections of necrotic foci
Abscesses
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
chemical mediator and regulation of inflammation
- cell derived
- plasma protein derived
preformed mediator in cell derived
- histamine
- serotonin
location or sources of histamine
- mast cells
- basophils
- platelets
inflammation of prolonged duration
chronic inflammation
chronic inflammation is characterized by
◦ Infiltration with mononuclear cells
◦ macrophages,
◦ lymphocytes,
◦ plasma cells
◦ Tissue destruction,
◦ Repair
2 repairs of chronic inflammation
- angiogenesis
- fibrosis
the dominant cells of chronic inflammation
Macrophages
Chronic Inflammatory Cells
macrophage
plasma cell
eosinophils
mast cells
cells in the liver
kupffer cells
cells in the spleen and lymph nodes
histiocytes
cells in central nervous system
microglial cells
cells in lungs
alveolar macrophages
Classification of chronic inflammation
Nonspecific chronic
inflammation and Specific inflammation
(granulomatous inflammation)
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:
characterized by the presence of
granuloma
Specific inflammation
distinctive pattern of chronic
inflammation characterized by
aggregates of activated
macrophages that assume an
epithelioid appearance
Granulomatous inflammation
Two types of giant cells:
Foreign body-type giant cells
Langhans giant cells
which have irregularly scattered nuclei in
presence of indigestible materials
Foreign body-type giant cells
the nuclei are arranged peripherally in a
horse –shoe pattern
Langhans giant cells
Langhans giant cells typically seen in
tuberculosis, and sarcoidosis
Types of granulomas
Foreign body granuloma
Immune granulomas
Major causes of granulomatious inflammation
Bacterial, fungal, helminthic, protozoal, chlamydia
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 2 ways
– Regeneration of injured tissue
– Replacement by connective tissue
factors involve in tissue repair
- cell proliferation
- interaction between cells and extracellular matrix
Mechanisms regulating cell
populations/cellular proliferation
- Cell numbers can be altered by increased or decreased rates of stem cell input and cell death due to apoptosis
- Changes in the rates of
proliferation or differentiation
Processes in the proliferation of cells
- DNA replication
- Mitosis
Cellular Proliferation
* divided into three groups:
- . Continuously dividing (labile) tissues
- Stable tissues
- Permanent tissues
what is Continuously dividing (labile) tissues
- Cells are continuously proliferating
- Can easily regenerate after injury
- Contain a pool of stem cells
example of labile tissues or Continuously dividing tissuea
bone marrow, skin, epithelium
what is Stable tissues
Cells have limited ability to proliferate
* Limited ability to regenerate
* Can proliferate if injured
examples of Stable tissues
liver, kidney, pancreas
what is Permanent tissues
Cells can’t proliferate
* Can’t regenerate
* injury always leads to scar
Example of Permanent tissues
neurons, cardiac muscle
Three phases in granulation -
tissue
Phase of inflammation
Phase of demolition
Ingrowth of granulation tissue
a mechanical
reduction in the size of the defect.
Wound contraction
Sources of Growth Factors:
- Platelets, activated (TGF)
- Damaged epithelial cells, (EGF)
- Circulating serum growth factors,
- Macrophages, (angiogenic factor)
- Lymphocytes recruited to the area of injury
have the capacity to stimulate cell division and proliferation
Growth factors
main phases of cutaneous wound
healing
Inflammation
* Formation of granulation tissue
* ECM remodeling
Two forms of eCM
interstitial matrix and basement membrane
Functions of ECM
- provides mechanical support to tissues
- acts as a substrate for cell growth
2 types of Wound Healing
regeneration
repair by scarring
Two patterns of wound healing
Healing by first intention
Healing by second intention
process of granulation tissue in 3-5 days
- new blood vessels (angiogenesis)
- fibroblasts
By 24 hours
- clot forms
- neutrophils come in
- epithelium begins to regenerate
By 3-5 days
- macrophages come in
- granulation tissue is formed
- collagen begins to bridge incision
- epithelium increases in thickness
Weeks later
- granulation tissue gone
- collagen is remodeled
- epidermis full, mature
- eventually, scar forms
Factors that influence wound healing
Local Factors
Systemic Factors
local factors of wound healing
> Type, size, and location of the wound
* > Vascular supply
* > Infection
Ø Movement
Ø Ionizing radiation
systemic factors of wound healing
Circulatory status
Infection
Metabolic status
Nutritional deficiencies
Complications of Wound Healing
- Infection
- Deficient Scar Formation
- Wound Dehiscence
- Ulceration
- Excessive Scar Formation
- Keloid Formation
- Hypertrophic Scar
