Cell injury can result from various causes including oxygen deprivation, chemicals, infections, and physical trauma. The cell responds through adaptation, reversible injury, or irreversible injury leading to necrosis or apoptosis. Necrosis is pathological cell death that occurs with ischemia or toxins. The inflammatory response is triggered by cell injury and aims to eliminate the cause of injury and initiate repair. Acute inflammation is characterized by increased blood flow, vascular permeability, and leukocyte recruitment over hours to days. Chronic inflammation is a prolonged response lasting weeks to months, where tissue destruction and repair occur simultaneously.

1. Cell injury and Inflammatory
response
Presenter: Dr. Olifan G (Ortho R1)
moderator: Dr. Bruh K.(Orthopedic surgeon)
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2. Cell injury
• Outline
Introduction
Cellular adaptation
Causes of cell injury
Mechanism of cell injury
Morphologic features of cell injury
Inflammation and its cascades
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3. Introduction
• Cells tend to maintain relatively constant intracellular
environment=homeostasis
• Cells are constantly adjusting their structure and
function to accommodate changing demands and
extracellular stresses=adaptation
• If the adaptive capability is exceeded or if the external
stress is inherently harmful, cell injury develops
• Cell injury - is a sequence of events that follows When
the cell is exposed to an injurious agent or stress
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4. • When a cell is exposed to an injurious agent,
the possible outcomes are:
1. Adaptation
2. Reversible injury or
3. Irreversible injury & may die via either
by necrosis or by apoptosis.
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5. • Apoptosis occurs when a cell dies through
activation of an internally controlled suicide
program.
• Apoptosis is designed to eliminate unwanted
cells , for example,during embryogenesis and
in various physiologic processes and certain
pathologic conditions.
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6. Necrosis
• Necrosis is the type of cell death that occurs
after ischemia and chemical injury or exposure
to toxins and infections
• Necrosis is always pathologic.
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7. Patterns of Tissue Necrosis
• Coagulative necrosis- the component cells are dead but the
basic tissue architecture is preserved for at least several days &
is characteristic of infarcts (areas of ischemic necrosis) in all solid
organs except the brain
• Liquefactive necrosis- seen in focal bacterial or, occasionally,
fungal infections. inflammatory cells and the enzymes of
leukocytes digest ("liquefy") the tissue(pus)
• Caseous necrosis- most often in foci of tuberculosis infection.
tissue architecture is lost
• Fat necrosis- typically resulting from release of activated
pancreatic lipases into the substance of the pancreas and the
peritoneal cavity.
• Fibrinoid necrosis-usually seen in immune reactions involving
blood vessels. Seen only by microscope
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8. 8

9. Cellular adaptation
• Reversible change in the size, shape, structure,
and function of cell in response to change in their
env’t.
• It can be physiologic or pathologic
Physiologic
Eg. Breast and uterine enlargement during px
Pathologic
Eg. LVH
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10. includes
I. Hypertrophy:- eg. SM, SKM, CM
II. Hyperplasia:- can be physiologic(hormonal&
compensatory. eg. Liver after lobectomy) or
pathologic(HPV &endometrial hyperplasia)
III. Atrophy:- disuse,loss of innervation, diminished
blood supply, inadequate nutrition, loss of
endocrine stimulation, and aging (senile atrophy)
IV. Metaplasia:- columnar Metaplasia, Squamous
metaplasia, Osseous metaplasia
V. NEOPLASIA
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11. Causes of cell injury
• Oxygen Deprivation eg. Ischemia, hypoxia
• Chemical Agents eg. Hyperglycemia, hypernatremia,
poisons,toxins
• Infectious Agents
• Immunologic Reactions
• Physical Agents
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12. Mechanisms of injury
• ATP depletion - failure of energy-dependent functions →
reversible injury → necrosis.
• Damage to mitochondria -ATP depletion → failure of energy-
dependent cellular functions → ultimately, necrosis.
• Influx of Ca - activation of enzymes that damage cellular
components and may also trigger apoptosis.
• Oxidative stress(ROS)- is an excess of these free radicals-
modification of cellular proteins, lipids, nucleic acids
• Defects in membrane permeablity- may affect plasma
membrane, lysosomal membranes, mitochondrial
membranes; typically culminates in necrosis.
• DNA damage- triggers apoptosis
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13. ATP depletion
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14. Damage to mitochondria
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15. Influx of Ca
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16. Oxidative stress
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17. Defects in membrane permeablity
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18. Inflammation
Acute inflammation
Chemical mediators of inflammation
Morphologic features of acute inflammation
Course of acute inflammation
Chronic inflammation
Systemic manifestation of inflammation
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19. Introduction
• Definition: is a protective response intended to eliminate
the initial cause of cell injury as well as the necrotic cells
and tissues resulting from the original insult
• Destined to localize and eliminate the causative agent and
to limit tissue injury.
• It is a physiologic (protective) response to injury
• Although inflammation helps clear infections and other
noxious stimuli and initiates repair, it can cause
considerable harm
• It is classified crudely into acute and chronic inf/n.
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20. The steps of the inflammatory response
can be remembered as the five Rs:
(1) Recognition of the injurious agent
(2) Recruitment of leukocytes
(3) Removal of the agent
(4) Regulation (control) of the response, and
(5) Resolution (repair)
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21. Causes:
• Causes of inflammation are apparently causes of
diseases such as
 Physical agents - mechanical injuries, alteration in
temperatures and pressure, radiation injuries.
 Chemical agents- drugs and toxins.
 Biologic agents (infectious)- bacteria,viruses,fungi,
parasites
 Immunologic disorders- hypersensitivity reactions,
autoimmunity, etc.
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22. ACUTE INFLAMMATION
• Immediate and early response to an injurious agent
• Relatively of short duration, lasting for minutes,
several hours or few days.
• Characterized by exudation of fluids and plasma
proteins and the emigration of leucocytes (N) to the
site of injury.
The five cardinal signs of acute inflammation
Redness (rubor)
Heat (calor)
Swelling (tumor)
Pain (dolor),
Loss of function 22

23. Stages of acute inflammation:
• It is categorized into an early vascular and a late
cellular responses.
• Both of them mediated by chemical mediators
Vascular response
a. Immediate (momentary) vasoconstriction= due to
neurogenic or chemical stimuli
b. Vasodilatation of arterioles and venules= due to
histamines, nitric oxide, etc.
c. slowing of blood flow & stasis = due to increased
vascular permeability most remarkably seen in the
post-capillary venules.
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24. • Mechanisms of increased permeability
– Formation of endothelial gaps in venules mediated
by histamine, bradykinin, leukotriens, Cytokines
such as (IL-1, TNF, and IFN-γ)
– Direct endothelial injury, resulting in endothelial cell
necrosis and detachment following burn, DIC,
bacteremia, etc.
– Delayed prolonged leakage following apoptosis
• All mechanism can occur in combination.
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25. 25

26. Cellular response;
leukocyte recruitment and activation
• It has the following stages:
A. Margination, rolling, & adhesion of leukocytes
(selectins, Igs, integrins,)
B. Transmigration of leukocytes between endothilial
cell(venules and small veins but only occasionally from
capillaries.) then migration to in interstitial tissues
C. Chemotaxis mediated by chemotactic factors(C5a,
LB4, IL-8, bacterial endotoxins, and cell debris)
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27. 27

28. D. Phagocytosis
• It is the process of engulfment and internalization of
particulate material,
Steps
1. Recognition and attachment
• Phagocytosis is enhanced if the material to be
phagocytosed is coated with opsonins(Fc frangment of
igs,c3b, c3bi , lecithin).
2. Engulfment complete enclosure of the particle within
the phagosome
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29. 3. Killing or degradation
 There are two mechanism of bacterial killing
A. Oxygen-independent mechanism
• This is mediate by some of the constituents of the
primary and secondary granules of PML.
These include:
Bactericidal permeability increasing protein (BPI)
Lysozymes
Lactoferrin
Major basic protein
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30. B. Oxygen-dependent mechanism:
 Mediated by formation ROS
 There are two types of oxygen- dependent
killing mechanisms
i) Non-myeloperoxidase dependent
Mediated by H2O2, super oxide (O2) and hydroxyl
ion (HO-) and possibly single oxygen (1O2).
ii) Myloperoxidase–dependent
Mediated by H2O2 – halide - myecloperoxidease
system which converts H2O2 to HOCI (hypochlorous
radical).
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32. Chemical mediators of inflammation
• Inflammation has the following sequence:
Cell injury Chemical mediators Acute inflammation (i.e. the
vascular & cellular events).
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33. • Sources of mediators:
a) Plasma-derived mediators:
i) Complement activation:
– increases vascular permeability (C3a,C5a)
– activates chemotaxis (C5a)
– opsoninization (C3b,C3bi)
– Membrane attack complex (MAC(C5b-9)
ii) Factor XII (Hegman factor) activation:
– Its activation results in recruitment of four
systems: the kinin, the clotting, the fibrinolytic
and the compliment systems
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34. b) Cell-derived chemical mediators:
Cellular
mediators
Cells of origin function
histamine Mast cells, basophils Vascular leakage
serotonin platelets Vascular leakage
Lysosomal
enzymes
neutrophils Bacterial & tissue destruction
prostaglandins All leukocytes Vasodilation ,pain, fever
leukotriens All leukocytes LB4- chemo attractant
LC4,LD4,LE4- broncho &
vasoconstriction
Platelet
activating factor
All leukocytes Bronchoconstriction & WBC priming
Activated oxygen
spp
All leukocytes Endothelial & tissue damage
NO Macrophages Leukocyte activation
cytokines Lymphocytes,
Macrophages
Leukocyte activation
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35. Morphology of acute inflammation
There are different morphologic types of
acute inflammation:
Serous inflammation
• characterized by the outpouring of a
watery, relatively protein-poor fluid.
• e.g peritoneal, pleural, and pericardial
cavities & skin blister
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36. Fibrinous inflammation
• consequence of more severe injuries, resulting in
greater vascular permeability that allows large
molecules (such as fibrinogen) to pass the
endothelial barrier.
• e.g inflammation in the lining of body cavities,
such as the meninges, pericardium, and pleura.
Suppurative (Purulent) inflammation
• presence of large amounts of purulent exudate
(pus) consisting of neutrophils, necrotic cells,
and edema fluid.
• e.g. staphylococci are more likely to induce
such localized suppuration
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37. Catarrhal inflammation
• inflammation of mucus membranes in one of the
airways or cavities of the body.
• Result in thick exudate of mucus & WBCs due to
swelling of mucus membranes
• E.g common cold
Pseudomembranous inflammation
• inflammatory response to a powerfull necrotizing
toxin, such as diphteria toxin that results in
relatively large tenacious membrane –like
covering.
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38. Effects of acute inflammation
A. Beneficial effects
Dilution of toxins:
Protective antibodies:
Fibrin formation:
Cell nutrition:
Promotion of immunity:
B. Harmful effects
Tissue destruction
Swelling
Inappropriate response
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39. Course of acute inflammation
• Acute inflammation may end up in:
 Resolution
 Healing by fibrosis (scar formation)
 Abscess formation
 Chronic inflammation
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40. Outcomes of acute inflammation: resolution, healing by scarring (fibrosis), or chronic
inflammation
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41. Phagocytes clear the fluid, leukocytes and dead tissue, and fluid
and proteins are removed by lymphatic drainage
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42. CHRONIC INFLAMMATION
• a prolonged inflammatory process (weeks or months)
where an active inflammation, tissue destruction and
attempts at repair are proceeding simultaneously.
• Causes
1. Persistent infections- TB, leprosy
2. Prolonged exposure to nondegradable but
partially toxic substances- asbestos, silica
3. Progression from acute inflammation- uncollapsed
abscess cavities, foreign body, sequesterum in
osteomyelitis,
4. Autoimmuniy- RA, SLE
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43. Morphology
• Monocytes and Macrophages are the primary
cells in chronic inflammation
• T-Lymphocytes :
• B-lymphocytes and Plasma cells :
• Mast cells and eosinophils :
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44. Characteristics Acute inflammation Chronic
inflammation
Duration Short Relatively long
Pattern Stereotyped Varied
Predominant cell Neutrophils,
Lymphocytes
Macrophages,
plasma cells
Tissue destruction Mild to moderate Marked
Fibrosis Absent Present
Inflammatory
reaction
Exudative Productive
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45. SYSTEMIC EFFECTS OF INFLAMMATIONS
• The systemic effects of inflammation include:
a. Fever
b. Endocrine & metabolic responses
c. Autonomic responses
d. Behavioral responses
e. Leukocytosis
f. Leukopenia
g. Weight loss
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46. a. Fever
– It is coordinated by the hypothalamus & by
cytokines (IL -1, IL-6, TNF-α)
b. Endocrine and metabolic responses include:
The liver secrets acute phase proteins such as:
• C-reactive proteins
• Complement and coagulation proteins(ESR)
 Glucocorticoids (increased)
c. Autonomic responses include:
Redirection of blood flow from the cutaneous to
the deep vascular bed.
Pulse rate (increased)
Sweating (decreased)
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47. d. Behavioral responses include:
– Rigor, chills, anorexia, and malaise
e. Leukocytosis-
Its usual count is 15,000 to 20,000 cells/mm3.
Neutrophilia, lymphocytosis, eosinophilia.
f. Leukopenia -is also a feature of typhoid fever and
some parasitic infections.
g. Weight loss –
- due to the action of IL-1 and TNF-α which increase
catabolism in skeletal muscle, adipose tissue and the
liver with resultant negative nitrogen balance.
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48. References
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