GENERAL

GENERAL
PATHOLOGY
PATHOLOGY
CELLULAR INJURY
CELLULAR INJURY
CELL DEATH
CELL DEATH
GENERAL PATHOLOGY
GENERAL PATHOLOGY

A discipline involving basic science and

A discipline involving basic science and
clinical practice
clinical practice

Devoted to the study of

Devoted to the study of
structural
structural
and
and
functi onal
functi onal
changes in the cells, tissues,
changes in the cells, tissues,
and organs that underlie disease
and organs that underlie disease
GENERAL PATHOLOGY
GENERAL PATHOLOGY

DIVISIONS OF PATHOLOGY
DIVISIONS OF PATHOLOGY

GENERAL PATHOLOGY
GENERAL PATHOLOGY

Concerned with the basic reactions of an

Concerned with the basic reactions of an
injured cell to various nonspecific stimuli
injured cell to various nonspecific stimuli
O
SYSTEMIC PATHOLOGY
SYSTEMIC PATHOLOGY

Studies and examines the specific

Studies and examines the specific
responses of special cells and tissues and
responses of special cells and tissues and
organs to more or less well defined stimuli
organs to more or less well defined stimuli
FOUR ASPECTS OF DISEASE
FOUR ASPECTS OF DISEASE
PROCESS
PROCESS

ETIOLOGY/CAUSE
ETIOLOGY/CAUSE

PATHOGENESIS
PATHOGENESIS

MORPHOLOGIC CHANGES
MORPHOLOGIC CHANGES

CLINICAL SIGNIFICANCE
CLINICAL SIGNIFICANCE
+
These form the basic CORE of the
These form the basic CORE of the
study of PATHOLOGY
study of PATHOLOGY
ETIOLOGY
ETIOLOGY
Refers to CAUSES of the disease
Refers to CAUSES of the disease
Two major classes of etiologic factors:
Two major classes of etiologic factors:
intrinsic or genetic
intrinsic or genetic
;
;
acquired
acquired

one etiologic agent for one disease is no

one etiologic agent for one disease is no
longer significant
longer significant
MULTIFACTORIAL.
MULTIFACTORIAL.
PATHOGENESIS
PATHOGENESIS
The sequence of events in the response of
The sequence of events in the response of
the cells and tissues or organs to the
the cells and tissues or organs to the
cause
cause
From the beginning of the initial
From the beginning of the initial
stimulation to the ultimate expression or
stimulation to the ultimate expression or
manifestation of the disease
manifestation of the disease
MORPHOLOGIC CHANGES
MORPHOLOGIC CHANGES
These encompass the structural and
These encompass the structural and
functional alterations in cells or tissues
functional alterations in cells or tissues
that are either characteristic of the
that are either characteristic of the
disease or diagnostic of the etiologic
disease or diagnostic of the etiologic
process
process
MORPHOLOGIC CHANGES
MORPHOLOGIC CHANGES
The practice of diagnostic pathology is
The practice of diagnostic pathology is
devoted to the identification of the
devoted to the identification of the
nature and progression of the disease
nature and progression of the disease
by studying the
by studying the morphologic changes

in tissues and chemical alterations in
in tissues and chemical alterations in
patients.
patients.
FUNCTIONAL DERANGEMENTS
FUNCTIONAL DERANGEMENTS
Refer also to the CLINICAL
Refer also to the CLINICAL
MANIFESTATIONS
MANIFESTATIONS
The nature of the morphologic changes
The nature of the morphologic changes
and their distribution in the body influence
and their distribution in the body influence
and affect the normal function of the cells,
and affect the normal function of the cells,
tissues and organs
tissues and organs
These influence the clinical manifestations
These influence the clinical manifestations
(signs and symptoms), course, and
(signs and symptoms), course, and
prognosis of the disease
prognosis of the disease
CELLULAR INJURY AND
ADAPTATIONS
E
Normally, the cell is in a homeostatic,
steady state,able to handle normal
physiologic stimulation
E
But with more excessive physiologic
stresses or with pathologic stimuli, the cell
will undergo a series of events or
phenomena called CELLULAR
ADAPTATIONS, inorder to achieve an
altered, steady state, thus preserving its
viability.
Remember
E
Whether specific types of stress induce
an adaptive response, reversible injury
or cell death depends on the nature and
severity of the stress and on many
variables relating to the intrinsic state of
the cell itself.
Four intracellular systems
Four intracellular systems
that are prone to injury.
that are prone to injury.

Maintenance of the integrity of the

Maintenance of the integrity of the
cell membrane
cell membrane

Aerobic respiration/oxidative
Aerobic respiration/oxidative
phosphorylation and ATP production -
phosphorylation and ATP production -
mitochondrion
mitochondrion

Synthesis of enzymic and structural

Synthesis of enzymic and structural
proteins
proteins
RNA
RNA

Preservation of the genetic apparatus

Preservation of the genetic apparatus
-
-
DNA
DNA
Considerations to remember about
cell injury..

Morphologic changes of cell injury

becomes apparent only after some
critical biochemical system within the
cells has been deranged.

Injury at one locus leads to wide

ranging secondary effects
Further considerations about cell
injury.

Reactions of the cell to the

stimuli/injury depend on the
type, duration, and severity of
the stimuli

Consequences of cell injury

depend also on the type, state,
and adaptability of the cell.
BROAD CATEGORIES OF CAUSES
OF CELL INJURY
O
HYPOXIA
O
PHYSICAL AGENTS
O
CHEMICAL AGENTS/DRUGS
O
INFECTIOUS AGENTS
O
IMMUNOLOGIC REACTIONS
O
GENETIC PROBLEMS
O
NUTRITIONAL IMBALANCE
HYPOXIA/ISCHEMIC INJURY

Main point of attack: AEROBIC OXIDATIVE

RESPIRATION

Common causes:

Impediment of blood flow by arteriosclerosis

or thrombi

Inadequate oxygenation of the blood due to

cardio-respiratory failure

Loss of oxygen carrying capacity e.g. anemia

and carbon monoxide poisoning
HYPOXIA/ISCHEMIC INJURY

ACUTE CELLULAR SWELLING OR EDEMA one of

the earliest and most common manifestation of
ischemic injury
-
This is caused by impairment of cell volume
regulation by the plasma membrane
+
2 to ATP depletion => sodium will accumulate
intracellularly with diffusion of potassium out of
the cell
+
2 also to increased intracellular osmotic load due
to accumulation of catabolites
HYPOXIA

Hypoxia affects oxidative phosphorylation

Hence, synthesis of vital ATP is critical

membrane damage, which may lead to lethal
cell injury

CALCIUM is an important mediator of the

biochemical alterations leading to cell death
HYPOXIC CHANGES

Cellular swelling would result whenever cells

are incapable of maintaining ionic and fluid
homeostasis

Hydropic change or vacuolar degeneration,

for there are small, clear vacuoles that appear
within the cytoplasm, which came from
distended or pinched off in sequestered
segments of endoplasmic reticulum

When this affects all cells in an organ, the

organ grossly has some pallor, with increased
turgor, and increased weight
MORPHOLOGY OF INJURED
MORPHOLOGY OF INJURED
CELLS.
CELLS.

A. Ultrastructural Changes
A. Ultrastructural Changes
+
In the plasma membrane
In the plasma membrane
-
Cellular swelling
Cellular swelling
-
Formation of cytoplasmic blebs
Formation of cytoplasmic blebs
-
Blunting and distortion of microvilli
Blunting and distortion of microvilli
-
Appearance of myelin figures (which
Appearance of myelin figures (which
maybe deposited intracytoplasmic or
maybe deposited intracytoplasmic or
extracellularly)
extracellularly)
MORPHOLOGY OF INJURED
MORPHOLOGY OF INJURED
CELLS.
CELLS.
+
In the mitochondria
In the mitochondria
-
Swelling, rarefaction, appearance of
Swelling, rarefaction, appearance of
amorphous densities
amorphous densities
+
The endoplasmic reticulum becomes
The endoplasmic reticulum becomes
dilated with detachment and
dilated with detachment and
disaggregation of polysomes into
disaggregation of polysomes into
monosomes
monosomes
+
Nucleolar alterations and
Nucleolar alterations and
disaggregation of granular and
disaggregation of granular and
fibrillar elements
fibrillar elements
MORPHOLOGY OF INJURED
MORPHOLOGY OF INJURED
CELLS.
CELLS.

B. Light Microscopy Patterns

B. Light Microscopy Patterns
+
Can be reversible injuries (in the
Can be reversible injuries (in the
form of
form of
CELLULAR SWELLING OR
CELLULAR SWELLING OR
FATTY CHANGE) or cell death
FATTY CHANGE) or cell death
(NECROSIS)
(NECROSIS)
+
Fatty change- encountered in
Fatty change- encountered in
cells dependent on involved in
cells dependent on involved in
fat metabolism such as the
fat metabolism such as the
myocardial cells
myocardial cells
, and the
, and the
hepatocytes
hepatocytes
CELLULAR INJURY
REVERSIBLE AND
REVERSIBLE AND
IRREVERSIBLE INJURY
IRREVERSIBLE INJURY
CONSEQUENCE
CONSEQUENCE
IRREVERSIBLE INJURY
IRREVERSIBLE INJURY
4
Two critical events that consistently
Two critical events that consistently
characterize IRREVERSIBILITY:
characterize IRREVERSIBILITY:
O
Inability to reverse
Inability to reverse
mitochondrial
mitochondrial
dysfunction
dysfunction
O
Profound disturbance in the
Profound disturbance in the
membrane function
membrane function
Possible mechanisms of Membrane
Possible mechanisms of Membrane
Damage
Damage
O
Progressive Loss of Phospholipids
Progressive Loss of Phospholipids

Due to activation of endogenous

Due to activation of endogenous
phospholipases, stimulated by
phospholipases, stimulated by
increased cytosolic calcium
increased cytosolic calcium

Due to also to decreased synthesis,

Due to also to decreased synthesis,
the steps of which are ATP
the steps of which are ATP
dependent
dependent
O
Cytoskeletal abnormalities
Cytoskeletal abnormalities

Due to increased proteases

Due to increased proteases

Results in the detachment of the cell

Results in the detachment of the cell
membrane from the cytoskeleton,
membrane from the cytoskeleton,
rendering the membrane susceptible
rendering the membrane susceptible
to stretching and possible rupture
to stretching and possible rupture
Possible Mechanisms of Membrane
Possible Mechanisms of Membrane
Damage
Damage
O
Presence/Formation of toxic oxygen
Presence/Formation of toxic oxygen
radicals
radicals

Free radical production is increased

Free radical production is increased
during reperfusion=>Reperfusion
during reperfusion=>Reperfusion
Injury
Injury

Radicals are produced by the

Radicals are produced by the
polymorphonuclears that infiltrate
polymorphonuclears that infiltrate
the site of ischemia during
the site of ischemia during
reperfusion
reperfusion
Possible Mechanisms of Membrane
Possible Mechanisms of Membrane
Damage
Damage
Possible Mechanism of Membrane
Possible Mechanism of Membrane
Damage
Damage
O
Presence of lipid breakdown products
Presence of lipid breakdown products

These have detergent-like effect on

These have detergent-like effect on
the membrane
the membrane

Accumulation of phospholipid
Accumulation of phospholipid
catabolic products during
catabolic products during
degradation
degradation

In the form of unesterified FFA, acyl

In the form of unesterified FFA, acyl
carnitine, and lysophospholipids
carnitine, and lysophospholipids
My inspiration.
My inspiration.
OXYGEN DERIVED RADICALS
E
SUPEROXIDE

Generated either directly during

autooxidation in the mitochondrion, or
enzymatically by cytoplasmic enzymes
like the oxidases and P-450

O2 oxidase = O2-

Once formed, O2- can be inactivated by

the enzyme SUPEROXIDE DISMUTASE
(SOD) to form H2O2
OXYGEN DERIVED RADICALS
E
HYDROGEN PEROXIDE

Produced either by the dismutation of

O2- or by oxidases present in the
peroxisomes (catalase-containing
organelles)

O2- + O2- + 2H+ SOD = H2O2

+ O2
OXYGEN DERIVED RADICALS
E
HYDROXYL RADICALS- CAUSED BY:
O
Hydrolysis of H2O caused by ionizing
radiation
O
Interaction of transitional metals
(copper and iron) in Fenton reaction
O
Through the Haber-Weiss reaction
Effects of these radicals are on
the MEMBRANE, LIPID
PEROXIDATION, SULHYDRYL
BONDS of proteins.
And also on the nucleotides of the
DNA.
SYSTEMS THAT MAY INACTIVATE OR
SYSTEMS THAT MAY INACTIVATE OR
TERMINATE THESE RADICALS
TERMINATE THESE RADICALS

Antioxidants either endogenous or

Antioxidants either endogenous or
exogenous
exogenous
+
Vitamin E, Vitamin C, sulfhydryl
Vitamin E, Vitamin C, sulfhydryl
containing substance amino acid like
containing substance amino acid like
cysteine, glutathione, and D-
cysteine, glutathione, and D-
penicillamine, ceruloplasmin, and
penicillamine, ceruloplasmin, and
transferrin
transferrin

Enzymes
Enzymes
+
Superoxide dismutase converts
Superoxide dismutase converts
superoxide to hydrogen peroxide
superoxide to hydrogen peroxide
+
Catalase decomposes H2O2
Catalase decomposes H2O2
+
Glutathione peroxide catalyzes the
Glutathione peroxide catalyzes the
ability of reduced glutathione to release
ability of reduced glutathione to release
hydrogen from sulfhydroxyl to
hydrogen from sulfhydroxyl to
hydroxyl radical or to hydrogen
hydroxyl radical or to hydrogen
peroxide
peroxide
SYSTEMS THAT MAY INACTIVATE OR
SYSTEMS THAT MAY INACTIVATE OR
TERMINATE THESE RADICALS
TERMINATE THESE RADICALS
MICROSCOPIC CHANGES OF
MICROSCOPIC CHANGES OF
INJURIES
INJURIES

IF DUE TO REVERSIBLE INJURY:

IF DUE TO REVERSIBLE INJURY:
CELLULAR SWELLING OR FATTY
CELLULAR SWELLING OR FATTY
CHANGE
CHANGE

IF DUE TO IRREVERSIBLE INJURY:

IF DUE TO IRREVERSIBLE INJURY:
NECROSIS; APOPTOSIS; CELL DEATH
NECROSIS; APOPTOSIS; CELL DEATH
NECROSIS
NECROSIS
Morphologic changes that follow cell
Morphologic changes that follow cell
death in a living tissue or organ resulting
death in a living tissue or organ resulting
from the degradative action of enzymes
from the degradative action of enzymes
on the lethally injured cells
on the lethally injured cells
Secondary to:
Secondary to:
1.
1.
Enzymic digestion of cells
Enzymic digestion of cells
2.
2.
Denaturation of proteins
Denaturation of proteins
NECROSIS
NECROSIS
Nuclear changes associated with cell
Nuclear changes associated with cell
death/necrosis :
death/necrosis :
+
Pyknosis
Pyknosis
nuclear shrinkage with small,
nuclear shrinkage with small,
dense, wrinkled chromatin material
dense, wrinkled chromatin material
+
Karyolysis
Karyolysis
dissolution of the chromatin
dissolution of the chromatin
pattern due to hydrolytic action of the
pattern due to hydrolytic action of the
DNASES of the lysosomes
DNASES of the lysosomes
+
Karyorrhexis
Karyorrhexis
break up of the
break up of the
nucleus into
nucleus into
many clumps
many clumps

APOPTOSIS
APOPTOSIS

dropping off process- single or cluster of cells

dropping off process- single or cluster of cells
which are round or oval masses with
which are round or oval masses with
eosinophilic cytoplasm and dense chromatin
eosinophilic cytoplasm and dense chromatin
pattern become dropped off
pattern become dropped off
These represent fragmented cells which are
These represent fragmented cells which are
taken up and degraded by phagocytic cells
taken up and degraded by phagocytic cells
This process is responsible for the destruction of
This process is responsible for the destruction of
cells during embryogenesis, and for hormone-
cells during embryogenesis, and for hormone-
dependent involution
dependent involution
Represented by Councilman bodies seen
Represented by Councilman bodies seen
commonly in liver hepatitis and toxicity
commonly in liver hepatitis and toxicity
NECROSIS vs APOPTOSIS
NECROSIS vs APOPTOSIS
Sequence of events in apoptosis
Sequence of events in apoptosis
The initial changes consist of nuclear
The initial changes consist of nuclear
chromatin condensation and
chromatin condensation and
fragmentation
fragmentation
Followed by cytoplasmic budding and
Followed by cytoplasmic budding and
phagocytosis of the extruded apoptotic
phagocytosis of the extruded apoptotic
bodies
bodies
Signs of cytoplasmic blebs and digestion
Signs of cytoplasmic blebs and digestion
and leakage of cellular components
and leakage of cellular components
happen
happen
Necrosis VS Apoptosis
Necrosis VS Apoptosis
TYPES OF NECROSIS
TYPES OF NECROSIS
4
COAGULATION NECROSIS
COAGULATION NECROSIS

Most common pattern

Most common pattern

Shows opaque, acidophilic

Shows opaque, acidophilic
tombstone cells
tombstone cells

Loss of nucleus, BUT WITH

Loss of nucleus, BUT WITH
PRESERVATION OF THE BASIC
PRESERVATION OF THE BASIC
SHAPE AND OUTLINE
SHAPE AND OUTLINE

Tissue architecture is still recognized

Tissue architecture is still recognized
TYPES OF NECROSIS
TYPES OF NECROSIS
4
COAGULATION NECROSIS
COAGULATION NECROSIS

Seen in the following organs during

Seen in the following organs during
ischemia: KIDNEYS, HEART,
ischemia: KIDNEYS, HEART,
ADRENALS
ADRENALS

2 to denaturation
2 to denaturation
COAGULATION NECROSIS OF
COAGULATION NECROSIS OF
THE HEART TISSUES
THE HEART TISSUES
TYPES OF NECROSIS
TYPES OF NECROSIS
4
LIQUEFACTION NECROSIS
LIQUEFACTION NECROSIS

Occurs when autolysis and heterolysis

Occurs when autolysis and heterolysis
prevail over conditions that favor
prevail over conditions that favor
denaturation
denaturation

2 to hydrolytic actions of enzymes

2 to hydrolytic actions of enzymes

Seen in ischemic destruction of brain and

Seen in ischemic destruction of brain and
kidney tissues which are converted to a
kidney tissues which are converted to a
cystic structure filled with cellular debris
cystic structure filled with cellular debris
and fluid
and fluid
hallmark of areas of past
hallmark of areas of past
bacterial infection
bacterial infection
LIQUEFACTION NECROSIS, BRAIN,
LIQUEFACTION NECROSIS, BRAIN,
GROSS
GROSS

4
As this infarct in the brain is
As this infarct in the brain is
organizing and being resolved, the
organizing and being resolved, the
liquefactive necrosis leads to
liquefactive necrosis leads to
resolution with cystic spaces.
resolution with cystic spaces.

4



LIQUEFACTION NECROSIS OF
LIQUEFACTION NECROSIS OF
KIDNEY TISSUE, MICROSCOPIC
KIDNEY TISSUE, MICROSCOPIC
TYPES OF NECROSIS
TYPES OF NECROSIS
4
CASEATION NECROSIS
CASEATION NECROSIS

Combination of coagulative and

Combination of coagulative and
liquefactive necrosis
liquefactive necrosis

Seen in tuberculous infection

Seen in tuberculous infection

Microscopically: cells are not totally

Microscopically: cells are not totally
liquefied nor are their outlines preserved
liquefied nor are their outlines preserved
creating a distinctive amorphous granular
creating a distinctive amorphous granular
debris and is enclosed within a
debris and is enclosed within a
granulomatous inflammatory wall
granulomatous inflammatory wall

Grossly: soft, friable, whitish gray cheesy

Grossly: soft, friable, whitish gray cheesy
surface
surface
Tuberculous Infection of the Lungs
Tuberculous Infection of the Lungs
Caseation Necrosis, Lung Tissue
Caseation Necrosis, Lung Tissue
TYPES OF NECROSIS
TYPES OF NECROSIS
4
FAT NECROSIS
FAT NECROSIS

SEEN AMONG ADIPOSE TISSUES

SEEN AMONG ADIPOSE TISSUES

Due to lipaseswhich catalyze the

Due to lipaseswhich catalyze the
decomposition of triglycerides that
decomposition of triglycerides that
leak from adjacent damaged adipose
leak from adjacent damaged adipose
cells to produce free fatty acids
cells to produce free fatty acids
which in return then become
which in return then become
complex with calcium
complex with calcium

form
form
CALCIUM SOAPS
CALCIUM SOAPS
FAT NECROSIS, MESENTERY,
FAT NECROSIS, MESENTERY,
GROSS
GROSS
FAT NECROSIS, PANCREAS,
FAT NECROSIS, PANCREAS,
GROSS
GROSS
FAT NECROSIS,
FAT NECROSIS,
PANCREAS,MICROSCOPIC
PANCREAS,MICROSCOPIC
4

4

Microscopically, fat necrosis adjacent to pancreas is
seen here. There are some remaining steatocytes at
the left which are not necrotic. The necrotic fat cells
at the right have vague cellular outlines, have lost
their peripheral nuclei, and their cytoplasm has
become a pink amorphous mass of necrotic
material.


FAT NECROSIS, BREAST,
FAT NECROSIS, BREAST,
MICROSCOPIC
MICROSCOPIC
4
In this view of fat necrosis at high magnification, some In this view of fat necrosis at high magnification, some
lipid-laden macrophages are seen between the necrotic lipid-laden macrophages are seen between the necrotic
adipose tissue cells. The most common etiology is trauma, adipose tissue cells. The most common etiology is trauma,
but fat necrosis of the breast can also occur with surgery but fat necrosis of the breast can also occur with surgery
and radiation therapy. and radiation therapy.
4




TYPES OF NECROSIS
TYPES OF NECROSIS
4
GANGRENOUS NECROSIS
GANGRENOUS NECROSIS

Applied to the lower extremities which has

Applied to the lower extremities which has
lost its blood supply
lost its blood supply

Coagulative necrosis modified by

Coagulative necrosis modified by
liquefaction action of the bacteria and
liquefaction action of the bacteria and
WBCs
WBCs

If coagulative process predominates: DRY

If coagulative process predominates: DRY
GANGRENE
GANGRENE

If liquefactive process predominates: WET

If liquefactive process predominates: WET
GANGRENE
GANGRENE
DRY GANGRENE, GROSS
DRY GANGRENE, GROSS
4
This is gangrene, or necrosis of many tissues in a
This is gangrene, or necrosis of many tissues in a
body part. In this case, the toes were involved in a
body part. In this case, the toes were involved in a
frostbite injury. This is an example of "dry"
frostbite injury. This is an example of "dry"
gangrene in which there is mainly coagulative
gangrene in which there is mainly coagulative
necrosis from the anoxic injury.
necrosis from the anoxic injury.

4



WET GANGRENE, GROSS
WET GANGRENE, GROSS
This is gangrene of the lower extremity. In this case the This is gangrene of the lower extremity. In this case the
term "wet" gangrene is more applicable because of the term "wet" gangrene is more applicable because of the
liquefactive component from superimposed infection in liquefactive component from superimposed infection in
addition to the coagulative necrosis from loss of blood addition to the coagulative necrosis from loss of blood
supply. This patient had diabetes mellitus. supply. This patient had diabetes mellitus.
4



GANGRENOUS NECROSIS,
GANGRENOUS NECROSIS,
MICROSCOPIC
MICROSCOPIC
4
Gangrenous necrosis involves the tissues of a
Gangrenous necrosis involves the tissues of a
body part. The inflammation seen here is
body part. The inflammation seen here is
extending beneath the skin of a toe to involve soft
extending beneath the skin of a toe to involve soft
tissue (fat and connective tissue) and bone.
tissue (fat and connective tissue) and bone.
Because multiple tissues are non-viable,
Because multiple tissues are non-viable,
amputation of such areas is necessary.
amputation of such areas is necessary.

4



OTHER FORMS OF INJURY
OTHER FORMS OF INJURY

CHEMICAL INJURY
CHEMICAL INJURY

Chemicals induce cell injury by one of

Chemicals induce cell injury by one of
two general mechanisms:
two general mechanisms:
1. 1.
Chemicals can act
Chemicals can act
directly
directly
by cmbining
by cmbining
with some critical molecular component
with some critical molecular component
or organelle
or organelle
2. 2.
Chemicals need to be converted to
Chemicals need to be converted to
reactive toxic
reactive toxic
metabolites or by product
metabolites or by product

which will act on target cells
which will act on target cells
CHEMICAL INJURY
CHEMICAL INJURY

Carbon tetrachloride poisoning prototype

Carbon tetrachloride poisoning prototype
of chemical injury
of chemical injury

Toxic effect is due to conversion of CCl4

Toxic effect is due to conversion of CCl4
by P-450 to the highly reactive toxic free
by P-450 to the highly reactive toxic free
radical CCl3
radical CCl3

CCL3 initiates lipid peroxidation

CCL3 initiates lipid peroxidation

membrane damage
membrane damage
OTHER FORMS OF INJURY
OTHER FORMS OF INJURY

VIRUS INDUCED INJURY

VIRUS INDUCED INJURY

CELLULAR CHANGES ARE SECONDARY TO: 1.

CELLULAR CHANGES ARE SECONDARY TO: 1.
CYTOLYTIC/CYTOPATHIC EFFECT
CYTOLYTIC/CYTOPATHIC EFFECT

2. Oncogenic effect stimulation of host cell

2. Oncogenic effect stimulation of host cell
replication and may produce tumors
replication and may produce tumors
+
DIRECT CYTOPATHIC EFFECTS HAVE HIGH
DIRECT CYTOPATHIC EFFECTS HAVE HIGH
DEGREE OF SPECIFICITY BECAUSE OF
DEGREE OF SPECIFICITY BECAUSE OF
MEMBRANE RECEPTORS ON HOST CELLS
MEMBRANE RECEPTORS ON HOST CELLS
SUNSET over Salt Lake City
GOOD DAY!!!!