Cell death

1. CHAPTER 2

2. Cell Injury, Death,
Inflammation, and Repair

3. CONTENTS:
•
•
•
•
Introduction
Adaptation of cells
Mechanisms
Adaptive disorders
Atrophy
Hypertrophy
Hyperplasia
Metaplasia
Dysplasia

4. Cellular Adaptation to Injury or
Stress
Injury or Stress
Increased stimulation
Decreased stimulation or
lack of nutrients
Chronic irritation
Adaptation
Hyperplasia or hypertrophy
Atrophy
Metaplasia or Dysplasia

5. INTRODUCTION:
• On exposure to stress, the cells make
adjustments with the changes in their
environment to:
* Physiologic needs
*Pathologic injury

6. MECHANISM:
•
•
•
Altered cell surface receptor binding.
Alterations in signal for protein synthesis.
Synthesis of new proteins by the target
cell such as heat-shock proteins.

7. ADAPTIVE DISORDERS OF
GROWTH in cell after cell injury:
•
•
•
•
•
1. SIZE
Change in Size-Atrophy
Change in Size-Hypertrophy
2. NUMBER:
Change in Number-Hyperplasia
3. DIFFERENTIATION OF CELLS:
Change in Shape-Metaplasia
Change in Shape-Dysplasia

8. D. Metaplasia

10. Muscle atrophy

11. HYPERTROPHY:
•
•
An increase in the size of the cells, which
results in enlargement of organ without
any changes in the number of cells.
Occurs due to increased functional
demand & hormonal stimulation.

12. CAUSES:
•
•
PHYSIOLOGIC:
Enlargement of uterus during pregnancy,
Skeletal muscle hypertrophy in person going
for GYM.
PATHOLOGIC:
Hypertrophy of cardiac muscle in Congestive
heart failure

13. HYPERPLASIA:
•An increase in number of parenchymal
cells, which results in enlargement of organ/
tissue.

14. CAUSES:
•
•
PHYSIOLOGIC:
HORMONAL:
Eg: Hyperplasia of uterus during
menstrual period
PATHOLOGIC:
Benign Prostatic Hyperplasia (BPH)
due to excess of Androgenic stimulation

15. METAPLASIA:
•
•
•
META-Transformation
PLASIA-Growth
Metaplasia (Greek: "change in form") is the
transformation of one differentiated cell type
to another differentiated cell type

16. CLASSIFICATION:
• MESENCHYMAL METAPLASIA:
*Osseous (bone) metaplasia
*Cartilaginous metaplasia

17. DYSPLASIA:
•
•
the presence of cells of an abnormal type
within a tissue, which may signify a stage
preceding the development of cancer.
Dysplasia (from Ancient Greek, "bad" or "
difficult" and plasis, "formation") is an
abnormal growth or development of cells
(microscopic scale) and/or organs
(macroscopic scale), and/or the abnormal
histology or anatomical structure presumably
resulting from such growth.

21. Cell injury

22. Definition of Cell injury
•
•
Cell injury is defined as a variety of stress,
a cell encounter as a result in changes in
its internal and external environment.
All cells of body have an inbuilt
mechanism to deal with changes in
environment to an extent.

23. Causes of Cell Injury
•
•
•
•
•
•
•
Physical Agents : trauma /physical injury
Chemical agents and Drugs : Acids, Alkali, Aspirin
Infectious Agents: Bacterial, Fungal, Viral etc
Oxygen deprivation : hypoxia or ischemia
Immunologic Reactions: Antigen / Antibody
reactions
Genetic Derangements : During cell cleavage
Nutritional Imbalances: Stomatitis in Riboflavin
deficiency, Scurvy in Vit C deficiency

24. Types of Cell Injury and cell Death
•
•

Reversible Cell Injury
Irreversible Cell Injury and it is of two
types
Necrosis – always pathologic
> Apoptosis – may be physiologic
or pathologic

27. TYPES OF CELL INJURY

28. Reversible and Irreversible Cell Injury

29. Reversible Cell Injury
normal kidney tubules reversibly injured
kidney tubules
•
•
•
Chromatin clumping
Membrane blebbing
Swelling of ER and
mitochondria (slight
eosinophilia)

30. Irreversible Cell Injury
normal kidney tubules irreversibly injured
kidney tubules
•
•
•
Nuclear fragmentation and
loss
Membrane disintegration
Swelling and rupture of ER,
mitochondria, & lysosomes
(marked eosinophilia)

31. Irreversible Cell Injury and Death

32. Irreversible Cell Injury and Death
Permanent loss of cell function irreversibly

33. Necrosis vs. Apoptosis

34. Regardless of the type or mechanism, extensive
cell injury results in death
either by necrosis or apoptosis
Necrosis
Loss of functional tissue
Impaired organ function, transient / temporary or
permanent
Apoptosis
Removal of damaged or unnecessary cells by
phagocytes

35. Patterns of Tissue
Necrosis
•
•
•
•
•
Coagulative
Necrosis
Liquefactive
Necrosis
Fat Necrosis
Caseous Necrosis
Fibrinoid Necrosis

36. Coagulative Necrosis
Pattern of cell death characterized by progressive loss of cell
structure, with coagulation of cellular constituents and persistence
of cellular outlines for a period of time, till inflammatory cells
arrive and degrade the remnants.

37. Liquefactive Necrosis
Pattern of cell death characterized by
dissolution of necrotic cells.
Typically seen in an abscess where there are
large numbers of neutrophils present, which
release hydrolytic enzymes that break down the
dead cells so rapidly that pus forms.
Pus is the liquefied remnants of dead cells,
including dead neutrophils.

38. Coagulative Necrosis Liquefactive Necrosis
KIDNEY

39. Caseous Necrosis
The pattern of cell injury that occurs with
granulomatous inflammation in response to
certain microorganisms (tuberculosis).
Granuloma is a collection of immune cells known as
macrophages / compact collection of cells of the
mononuclear phagocyte system

40. Caseous Necrosis in Tubersulosis

41. Fat Necrosis
Due to injury, Lipases (enzymes) are released
into adipose tissue, triglycerides are
cleaved into fatty acids, which bind and
precipitate calcium ions, forming insoluble
salts.
These salts look chalky white on gross
examination and are basophilic in
histological sections stained with
Hematoxylin & Eosin .

42. FAT NECROSIS

43. Fibrinoid Necrosis
The pattern of cell injury that occurs in
the wall of arteries in cases of
vasculitis.
There is necrosis of smooth muscle
cells of the tunica media and endothelial
damage which allows plasma proteins,
(primarily fibrin) to be deposited in the
area of medial necrosis.

44. FIBRINOID NECROSIS
Fibrinoidnecrosis
Fibrinoidnecrosis

45. –
•
–
Apoptosis-
Apoptosis- a falling away from
Definition: Programmed cell death
It is an active (energy-dependant) programmed single cell
death to delete the unwanted or defective cells
It has an important role in physiological processes and
pathological conditions
Apoptosis
Apoptosis

46. Apoptosis
–
•
•
–
•
Physiological processes:
During embryogenesis
During embryogenesis (implantation, organogenesis, developmental
involution, separation of digits in limb development)
Hormone -dependent involution
Hormone -dependent involution (endometrium during menstruation,
lactating breast after weaning)
Pathological conditions:
tumors
Cell death in tumors

47. Apoptosis

48. Necrosis Vs Apoptosis
•
•
•
•
•
•
Necrosis
Group of cells or part of
tissue
Passive process
Always pathologic
Mechanism is ATP
depletion, membrane
damage
Histology: Coagulation.
liquefaction
Causes inflammation
•
•
•
•
•
•
Apoptosis:
Single cell death in
living tissue
Active process
Physiologic or
Pathologic
Endonucleases has a
role here
Forms Apoptotic
bodies
Removed by
phagosytosis

49. Basic Mechanisms of Cell Injury

50. Mechanisms of Cell Injury
1.
2.
3.
4.
5.
Mitochondrial Damage & Depletion of ATP
Entry of Calcium into the cell
Increase reactive oxygen species (ROS)
Membrane Damage
DNA damage, Protein misfolding

51. Mitochondrial Damage &
Depletion of ATP

52. Cell Injury

54. ,

57. Pathologic Calcification

62. Cellular Accumulations
 Intracellular
 Extracellular

69. Fatty Liver

70. Fatty liver

71. Other Lipid Accumulations
Cholesterol and cholesterol esters – In
atherosclerosis, cholesterol accumulates in
smooth muscle cells and macrophages in the
intima of arteries

73. Intracellular Accumulation of
Proteins

75. Intracellular accumulations

86. Extra cellular accumulations

87. Amyloidosis
Amyloidosis

88. 1 2

89. AMYLOIDOSIS
•
•
Amyloid is a pathologic proteinaceous
substance, deposited between cells in various
tissues and organs of the body in a wide variety
of clinical settings.
Amyloidosis is not a single disease; rather it is a
group of diseases having in common the
deposition of similar-appearing proteins.

90. AMYLOIDOSIS

91. CLASSIFICATION OF
AMYLOIDOSIS
•
–
–
•
–
–
•
–
–
Based on cause
Primary : with unknown cause and the deposition is
because of disease itself
Secondary: as a complication of some underlying known
disease
Based on extent of amyloid deposition
Systemic (generalised) : involving multiple organs
Localised : involving one or two organs or sites
Based on histological basis
Peri-collagenous: corresponding in distribution to primary
amyloidosis
Peri-reticulin: corresponding in distribution to secondary
amyloidosis

92. CLASSIFICATION OF
AMYLOIDOSIS
•
–
–
–
•
–
–
•
Based on clinical location,
Pattern I: involving tongue, heart, bowel, skeletal and
smooth muscle, skin and nerves),
Pattern II: principally involving liver, spleen, kidney
and adrenals
Mixed pattern : involving sites of both pattern I and II
Based on tissues in which amyloid is deposited,
Mesenchymal : organs derived from mesoderm
Parenchymal: organs derived from ectoderm and
endoderm
Based on precursor biochemical proteins, into
specific type of serum amyloid proteins.

93. Constituents of Amyloid

94. •
•



2. A SET OF COMMON COMPONENTS FOUND
IN ALL AMYLOIDS (found in all cases of
amyloidosis):
The amyloid P component (AP) is a pentagonal protein that is
present in all types of amyloid.
Other molecular building blocks of basement membranes
present in amyloid are
Laminin,
Collagen type IV, and
The proteoglycan perlecan.

95. AL: Amyloid light-chain, Amyloid A (AA) amyloidosis ,, ATTR- transthyretin amyloidosis , SAA-Serum amyloid A (SAA) proteins

96. •
•
Light microscope: amyloid appears as
amorphous, eosinophilic, hyaline,
extracellular substance that gradually
encroaches on and produces pressure
atrophy of adjacent cells.
On congo red stain: amyloid gives a pink
or red color under ordinary light and an
apple green color under polarizing light.

97. Birefringence is the optical property

98. CHAPTER 3
INFLAMMATION , REPAIR
AND
WOUND HEALING

99. What is Inflammation?
Inflammation is defined as the local response of
living mammalian tissues to injury due to any
agent

100. Etiology










The causes of inflammation are many and varied:
Exogenous causes:
Physical agents
Mechanical agents: fractures, foreign corps, sand, etc.
Thermal agents: burns, freezing
Chemical agents: toxic gases, acids, bases
Biological agents: bacteria, viruses, parasites
Endogenous causes:
Circulation disorders: thrombosis, infarction, hemorrhage
Enzymes activation – e.g. acute pancreatitis
Metabolic products excess – uric acid, urea
Immune reactions e.g.allergic reactions, acute glomerulonephritis

101. Cardinal Signs of inflammation
•
•
•
•
•
Five cardinal signs of inflammation as (CDRTF)
Calor (Heat)
Dolor (Pain)
Rubor (Redness)
Tumor (Swelling)
Functio Laesa (Loss Of Function)

102. Changes/Events at The Injured
Site

103. •
•
Vascular events
Cellular events

104. Vascular events

105. Vascular events



At the site of injury, the changes occur in the
microvasculature consisting of arterioles,
venules and capillaries.
The changes are
Changes is the calibre of blood vessel and
blood flow
Structural changes that allows the plasma
proteins and blood cells to leak out of
vasculature

106. A. Changes in vascular calibre and
flow




Changes occur in the following order:
Vasoconstriction of arterioles to arrest bleeding (It
disappears within 3-5 seconds ) Active process
Vasodialation: Occur at late stage to increase the blood flow
which leads to rubor (redness) and calor (heat) Passive
process
Followed by Slowing of blood flow or stasis due to formation of
exudate and increased viscosity of blood

107. B. Increased vascular permeability (vascular
leakage)


A hallmark of acute inflammation (escape of a
protein-rich fluid).
It affects small & medium size venules, through
gaps between endothelial cells as follows

108. Exudation of Blood Constituents

109. 

Exudation is the leaking of blood constituents from
blood vessels into interstitial tissue (site of injury).
Exudate (or inflammatory edema) contains protein
and leukocytes
Fluid exudate Cellular exudate
Fluid exudate is formed by the plasma
constituents- fluid, solute and
proteins.
It may have the same chemical
composition as that of plasma
Circulating leucocytes constitute
the cellular exudate.
In most cases, the cells are
neutrophils and monocytes with
migration of Leukocyte along with
extravasation and phagocystosis

111. Cellular events

112. Leukocyte Extravasation






In the lumen, Leukocyte (cell) shows
following feature :
Margination,
Pavementing,
Rolling
Adheshion
Emigration and
Chemotaxis

113. In the lumen
•
•
Margination
Normally red and white cells flow
intermingled in the center of the vessel
separated from vessel wall by a clear
cell‐free plasmatic zone.
After injuryDue to slowing of the
circulation, leucocytes fall out of the axial
stream and come to periphery known as
MARGINATION

114. •
•
•
Pavementing‐ Neutrophils move close to
vessel wall
Rolling‐ Neutrophils roll over endothelial
cells
Adhesion‐ Binding to endothelial cells

115. Emigration
•
•
•
•
•
Neutrophils throw cytoplasmic
pseudopods migrate through
interendothelial
Spaces ‐ between endothelial cells &
basement membrane
Crosses basement membrane by
damaging it by collagenases
Escape of RBCs
Diapedesis also occurs - the passage of
blood cells through the intact walls of the

117. ICAM- intercellular Adhesion Molecule, LFA-1- Lymphocyte function-associated antigen

118. Chemotaxis
•
•
•
•
Leukocytes emigrate towards site of injury or chemical
gradient
Chemotactic agents: ‐
Exogenous – bacterial products
Endogenous ‐ complement system C5a, leukotrienes,
cytokines
Chemotactic agents bind to cell receptors on
leukocytes→ ↑cytosolic Ca2+ , ↑ phospholipases 
activation of leukocytes  production of arachidonic
acid metabolites  secretion of lysosomal enzymes 
secretion of cytokines ‐ modulation of leukocyte
adhesion molecules

119. 


1.
2.
3.
Phagocytosisis the process ofengulfment ofparticulate matters
such as microbes, immune complex, cellular debris by
PHAGOCYTES.
Neutrophils and Macrophages are the phagocytes.
Phagocytosis involves three distinct steps:
Recognition and attachment
Engulfment
Killing and degradation
Phagocytosis

120. PHAGOCYTOSIS

121. Stages of Phagocytosis

122. 



Step-1(Recognition and attachment):
Neutrophils and Macrophages recognize and attach
microbes by several membrane receptors.
Opsonization further enhances this step.
Opsonin is a substance capable of enhancing
phagocytosis by coating the microbes and making it
more active for binding to specific receptors

123. Step-2 (Engulfment):
Pseudopods (false foot) flow around the microbes and
enclose it within a phagosome formed by the plasma
membrane of the cell which fuses with the limiting
membrane of lysosomal granule forming phagolysosome

124. 
Step-3 (Killing and degradation):
It is the ultimate step in the elimination of infectious
agents i.e. the microbes within the phagocytes gets
killed and degraded

126. Chemical Mediators of Inflammation

127. Chemical Mediators of
Inflammation



Changes in inflammatory responses are due to
the production of chemical mediators in and
around the area.
These mediators performs their activity by
binding to specific receptors or by some
oxidative or enzymatic activity
These mediators can be derived from cells or
plasma

128. •
•
•
•
•
•
•
•
•
Chemical mediators from cells:
Histamine
Serotonin
Lysosomal enzymes
Prostaglandins
Leukotrienes and lipoxins
Platelet activating factors
Cytokines
Nitric oxide
Activated oxygen species

129. Cyclooxygenase And Lipoxygenase Pathways

130. The cyclooxygenase and lipoxygenase pathways
Injury

131.  Prostaglandins
Prostaglandin
s
contribute to vasodilation, capillary
permeability, and the pain and fever that accompany
inflammation.
The prostaglandin thromboxane A2 promotes platelet
aggregation and vasoconstriction.

132.  Leukotrienes
Leukotrienes C4 and D4 are recognizedas the primary
components of the slow reacting
substance of anaphylaxis (SRS-A) that causes slow and
sustained constriction ofthe bronchioles.

133. Types of Inflammation

134. •
–
–
–
Depending upon the defense capacity of the
host and duration of response, inflammation
can be classified as
Acute: Immediate and Short duration
Chronic: Long duration
Granulomatous: Due to granuloma formation

135. Acute Inflammation

136. Inflammation
•



–
–
The inflammatory reaction takes place at the microcirculation level
and it is composed by the following changes:
Tissue damage
Vascular response
Cellular changes
Metabolic changes & systemic manifestation
Tissue repair

137. Metabolic changes in inflammation

138. Metabolic changes
–
–
–
–
–
Protein metabolism
Is increased
Carbohydrate metabolism
Anaerobic (absence of oxygen) because of hypoxia with
increased formation of lactic and pyruvic acid;
Lipid metabolism
Increased formation of ketones and fatty acids
Mineral metabolism
Increased extracellular K+ concentration
Acid – base balance
Increased acid production Metabolic acidosis (ketones, lactic
acid) reduces plasma pH

139. Systemic Manifestations in
inflammation

140. Systemic Manifestations
–
–
–
Fever
Due to production of prostaglandins
Blood pressure
Increased pulse and blood pressure
Behavioral
Shivering (rigors), chills , anorexia (loss of
appetite), somnolence (day time sleep), and
malaise (not feeling well and body ache)

141. Systemic Manifestations
•
–
–
–
•
–
Leukocytosis: increased leukocyte count in the
blood may be due to
Increased Neutrophilia: bacterial infections
Increased Lymphocytosis: infectious mononucleosis,
mumps, measles
Increased Eosinophilia: Parasites, asthma, hay fever
Leukopenia: reduced leukocyte count may be
due to
Typhoid fever, some viruses, rickettsiae, protozoa

142. Outcomes of inflammation

143. Outcomes of inflammation
1.
–
–
Resolution
The complete restoration of the inflamed tissue back to a
normal status.
2. Fibrosis
Large amounts of tissue destruction, or damage is unable to
regenerate and fibrous scarring occurs in these areas of damage,
forming a scar composed primarily of collagen.

144. Outcomes of inflammation
–
–
3. Abscess formation
A cavity is formed containing pus, an opaque liquid containing
dead white blood cells and bacteria with general debris from
destroyed cells.
4. Chronic inflammation
After acute inflammation, if the injurious agent persists then
chronic inflammation will ensue characterized by the dominating
presence of macrophages in the injured tissue.

145. Normal Cell
Injury
Resolution Chronic Inflammation Puss Formation (Healing)
Normalcy Fibrosis

146. Types of Inflammation: acute vs. chronic
Types of repair: resolution vs. organization
(fibrosis)

147. Resolution

149. Chronic Inflammation

150. Chronic Inflammation
•
–
Inflammation of prolonged duration
(weeks or months)
Active inflammation, tissue destruction, and
attempts at repair are proceeding
simultaneously

151. Causes of Chronic Inflammation
•
–
•
–
–
•
–
Persistent infections
Treponema pallidum [syphilis], viruses, fungi,
parasites
Continuous Exposure to toxic agents
Exogenous: silica (silicosis)
Endogenous: toxic plasma lipid components
(atherosclerosis)
Autoimmunity
Rheumatoid arthritis, systemic lupus
erythematosus

152. Chronic Inflammation
•
–
–
–
Histological features
Infiltration with mononuclear cells
(macrophages, lymphocytes, and plasma
cells)
Tissue destruction (induced by the
inflammatory cells)
Healing by replacement of damaged tissue
by connective tissue (fibrosis) and new

153. Granulomatous Inflammation

154. Granulomatous Inflammation
•
–
–
Distinctive pattern of chronic inflammation
Predominant cell type is an ACTIVATED MACROPHAGE
with a modified epithelial-like (epithelioid) appearance
Giant cell may appear near injury (multinucleated giant
cell, multinucleate giant cell) is a mass formed by the
union of several distinct cells (usually histiocytes) may or
may not be present

155. Abscess formation

156. Abscess formation
•
•
•
The organisms or foreign materials kill the local cells,
resulting in the release of cytokines. The cytokines
trigger an inflammatory response, which draws large
numbers of white blood cells to the area and increases
the regional blood flow.
The final structure of the abscess is an abscess wall, or
capsule, that is formed by the adjacent healthy cells in
an attempt to keep away the pus from infecting
neighbouring structures.
However, such encapsulation tends to prevent immune
cells from attacking bacteria in the pus , thus may
worsen the condition.

157. Fibrosis

158. Fibrosis
Fibrosis (scarring) is the formation of excess fibrous connective tissue
in an organ or tissue in a reparative or reactive process as a result of
chronic inflammation.
Ex:
Pulmonary fibrosis, Cystic fibrosis
Idiopathic pulmonary fibrosis

159. Tissue Regeneration and
Repairing

161. Regeneration and Repairing






Repair is the replacement of injured or dead cells or tissues after injury
like inflammation, wounds, surgical resection by proliferation of viable
cells
Repair occurs by two distinct processes:
Regeneration- which restores normal tissues, and
Healing-which leads to scar formation and or fibrosis. Mostly, repair
occurs by a combination of these two processes
Repair begins early in inflammation within in 24 hours after injury
Repair involves the proliferation of different types of cells
and their interaction with the ECM (extracellular matrix).

165. 

Scar: The richly vascularized granulation tissue is
converted into a scar composed of spindle-shapped
fibroblasts, dense collagen, fragments of elastic
tissue and other ECM components. The scar is
collagenous at first and then a pale, avascular fibrous
scar is formed
Fibrosis: Refers to the heavy deposition of collagen
that occurs in organs such as lungs, liver and kidney
following chronic inflammatory processes or in the
myocardium after extensive ischemic necrosis
(infarction).

166. WOUND HEALING

167. WOUND
• It is a circumscribed injury which is caused by
external force and it can involve any tissue and
organ.

168. A cut or break in the continuity of any tissue, caused
by injury or operation.
WOUND

169. CLASSIFICATION OF
WOUNDS
Rank and Wakefield classification
a. Tidy wounds: are those made by sharp instruments and
contain no dead tissue, and which can be closed and allowed
to heal by primary intention.
b. Untidy wounds: are those caused by crushing or tearing and
contain dead tissue, and which cannot be closed by first
intention, hence heals by secondary intention.

170. Classification based on type of wound
Clean incised wound, Lacerated wound, Bruising,
stab, concussion and Contusion, Haematoma etc

171. Classification based on thickness of wound
a)
b)
c)
d)
e)
f)
Superficial wound
Partial thickness
Full thickness
Deep wounds
Complicated
wounds
Penetrating wound

172. a)
b)
c)
d)
Classification of surgical wounds
Clean wound
Clean contaminated wound
Contaminated wound
Dirty infected wound

173. HEALING
• Healing is the body’s response to injury in
an attempt to restore normal structure and
function.

174. A.
A.
The process of healing involves 2
distinct processes:
REGENERATION
REPAIR

175. • Regeneration: Is when healing takes place by
proliferation of parenchymal cells and usually
results in complete restoration of the original
tissues.

176. •
•
Repair: It is a healing outcome in which tissues
do not return to their normal architecture and
function.
Repair typically results in the formation of scar
tissue.

177. TYPES OF WOUND HEALING
•
•
Healing by first intention or primary intention
(wounds with opposed edges)
Healing by second intention or secondary
intention (wounds with separated edges)

178. Healing by first intention
(wounds with opposed
edges)






Healing of wound with following characteristics:
Clean and uninfected
Surgically incised
Without much loss of cells and tissue
Edges of wound are approximated by surgical sutures.
Wounds with opposed edges
Show primary union

179. •


•
The injury / incision causes
death of a limited number of epithelial cells
and connective tissue cells
disruption of only epithelial basal membrane
continuity
The narrow incisional space immediately after
the injury fills with clotted blood containing
fibrin and blood cells and its dehydration of
surface clot leads to formation of scab that
covers the wound.

180. Within 24 hours
•
•
Neutrophils appear at margins
of incision, moving toward fibrin
clot
Epidermis at its cut edges
thickens as a result of mitotic
activity of basal cells
•Within 24 to 48 hours, spurs of
epithelial cells from the both
edges migrate and grow along
the cut margins of the dermis,
depositing BM components as
they move. They fuse in the
the surface
midline beneath
scab, thus producinga
thin epithelial
continuous but
layer.

181. Within 24 to 48 hours
Spurs of epithelial cells from the both edges
migrate and grow along the cut margins of the
dermis, depositing BM components as they move
and they cover the scab but will be thin compared
to normal epithelial layer.

182. •
•
•
•
By day 3,
Neutrophils replaced by macrophages
Granulation tissue progressively invades incision space
Collagen fibers are now present in the margins of the incision, but at
first these are vertically oriented.
Epithelial cell proliferation continues leading to thickening of
epidermal covering layer

183. •
•
By day 5,
Incisional space is filled with granulation tissue
Neovascularization (new blood vessel formation) occurs
Collagen fibrils forms bridging the gap

184. During the second week
of collagen and
• Continued accumulation
proliferation of fibroblasts occurs
• There will be disappearance of Leukocytic
infiltrate, edema, and vascularity have largely
disappeared.

185. By the end of the first
month,
•
•
Scar comprises a cellular connective tissue devoid of
inflammatory infiltrate, covered now by intact epidermis.
Cell will completely restore to normal without any scar

186. Healing by second / secondary
intention

187. •
•
•
•
•
•
Wounds with wide separated edges
Show Secondary union
There will be more extensive loss of cells
and tissue
Regeneration of parenchymal cells
cannot completely reconstitute the original
architecture.
Abundant granulation tissue grows in
from the margin to complete the repair.
Complete restoration of cell is not
possible and results in scar

188. 1st intention 2nd intention
Inflammatory reaction is
less intense
Inflammatory reaction is
more intense
Very less amounts of
granulation tissue are
formed
Much larger amounts of
granulation tissue are
formed
Very less or no wound
contraction
Wound contraction
occurs in large surface
wounds
No Substantial scar
formation or thinning of
the epidermis
Substantial scar formation
and thinning of the
epidermis occurs
Difference between 1˚ & 2˚ union
of wound

189. FACTORS AFFECTING WOUND
HEALING:
1)
i.
ii.
iii.
iv.
v.
vi.
vii.
Local factors:
Infection
Presence of
necrotic tissue and
foreign body
Poor blood supply
Venous or lymph
stasis
Tissue tension
Hematoma
Large defect or
poor apposition
i.
ii.
iii.
iv.
v.
vi.
vii.
viii.
ix.
Age, obesity,smoking
Malnutrition, zinc, copper
Vitamin deficiency (vit C, vit A)
Anemia
Malignancy
Jaundice
Diabetes
HIV and immunosupressive
diseases
Steroids and cytotoxic drugs
2) General factors:

190. Gangrene

191. Gangrene

192. Gangrene
•
•
Gangrene
It’s a death and putrefaction of the
affected tissue while attached to living
body
Necrosis
Death of affected tissue with absence of
infection

193. Gangrene
Gangrene result from direct damage to the tissue caused
by mechanical, physical or chemical agent or by bacteria

194. Clinically gangrene classified to

195. TYPES OF GANGRENE
•
•
•
DRY GANGRENE
WET / Moist GANGRENE
GAS GANGRENE

196. •
•
•
Dry gangrene
This is mostly due to arterial occlusion
Its like mummification of the tissue which
becomes dry and reduced in volume
Putrefaction is always absent
Note: Putrefaction is the process of decay or rotting in a body

197. DRY GANGRENE

198. DRY GANGRENE

199. DRY GANGRENE
YUCKY!!!

200. Local symptoms of gangrene
•
•
•
Dry gangrene
The tissue become change in appearance
and diminish in volume
The skin become shriveled
The hair become dry and erect

201. Clinically gangrene classified to
•
•
•
Wet / Moist gangrene
This mostly due to venous occlusion
The affected tissue become disintegrated and
liquefied
The lesion contain volatile products of very bad
odor

202. Clinically gangrene classified to
• Also wet / moist gangrene contain soluble
poison when it is absorbed to the
circulation it will cause a fatal toxemia

203. WET / MOIST GANGREEN

204. WET / MOIST GANGRENE

205. WET / MOIST GANGRENE

206. Local symptoms of gangrene
•
•
Wet / Moist gangrene
The tissue is become purple, greenish, blackish
in color and increase in volume with engorged in
blood and serum
Pain is severe before death of the affected part

207. Clinically gangrene classified to
•
•
Gas gangrene
Its caused by many types of anaerobic
spore forming bacteria
They produce gas from the lyses of dead
tissue which appear as bubble In the
infected tissue

208. GAS GANGRENE

209. GAS GANGRENE

210. GAS GANGRENE

211. Local symptoms of gangrene
•
•
Gas gangrene
Gas gangrene causes very painful
swelling.
The skin turns pale to brownish-red. If you
press on the swollen area with your
fingers, you may feel gas as a crackly
sensation.

212. Clinically Prognosis of gangrene
•
•
Depend in the natural of the lesion which may
vary from a simple ulcer to the sloughing of a
large mass of a tissue.
Gangrene is dangerous when the toxemia is
severe which may cause death with in 24h of
onset

214. Treatment of gangrene

215. Treatment of gangrene
• The best treatment of gangrene is
amputation of the part from the body

216. Treatment of gangrene
•
•
Removal of the affected tissue
In case of moist gangrene we can make
scarification of affected with knife or
puncture the gangrenous tissue to permit
the escape of toxic liquid and allowing the
introduction of antiseptic inside the lesion

217. Treatment of gangrene
•
•
Application of counter-irritant at the periphery of
the affected part
This will cause increasing of hyperemia
(increases blood flow) to affected part which
favours phagocytosis near the affected tissue
which accelerate the separation of the moist or
dry gangrene from the health tissue.

219. END