Cell Injurv

:
Cellular !njury
(year 2010 )
Dr. Huda N.Zahawi, FRC.Path.
Cell Injurv:
'67ic Outline
Causes of cell injury
Types of !njury
Priciples S Nechanisms of cell injury
Outcome : ?Reversible ? !rreversible
Norphology
Adaptation to !njury
Patterns S types of Cell Death
Process of Aging
Cell Injurv:
Cellular !njury S Ada7tati6n
!ormal cell is in a steady dynamic state
¨Homeostasis" :
The ability or tendency of an organism or
cell to maintain internal equilibrium by
adjusting its physiological processes.
Cell Injurv:
Cells are constantly exposed to stresses.
!ormal physiologic stress
Severe stresses: injury results, and alters
the normal steady state of the cell,
consequently,
!t can survive in a damaged state and
ada7t t6 the injury
(reversible injury 6r ada7tati6n)
!t can die
(irreversible injury 6r cell death).
#
CELL
STRESS INJURY
Atrophy
Hypertophy
Hyperplasia
Metaplasia
Cellular swelling
Vacuolar change
Fatty change
Necrosis
Apoptosiss
Irreversible Irreversible
iniury iniury
Reversible Reversible
iniury iniury
Adaptation Adaptation
Cell Injurv:
Causes 6 Cell !njury
Hypoxia and ischemia
Free radicals
Chemical agents
Physical agents
!nfections
!mmunological reactions
Cenetic defects
!utritional defects
Aging
Cell Injurv:
'PES OF !N]UR
Cell Injurv:
Causes of Hypoxia
low levels of oxygen in the air
poor or absent Hemoglobin function
decreased erythropoiesis
respiratory or cardiovascular diseases,
or ischemia (reduced supply of blood)
1· Hy76ia S !schemia
Cell Injurv:
!schemia S Hypoxia induce mitochondrial
damage.
This results in decreased ATP which in
turn reduces energy for all cell functions !
!f persistent F CELL DEATH
Cell Injurv:
Hypoxia is a common cause of cell injury
Result : Cell resorts to anaerobic glycolysis
!schemia is the commonest cause of
hypoxia, S injures the cells faster than pure
hypoxia
Why ??
Restoration of blood may lead to recovery
OR !schemia/ Reperfusion injury F
Progressive cell damage
Examples : Nyocardial S Cerebral infarction
Cell Injurv:
!schemia/Re7erusi6n !njury
Restoration of blood flowF influx of high
levels of calcium
Reperfusion increases recruitment of
inflammatory cells F ree radical injury
Damaged mitochondria induce free radical
production S compromise antioxidant defense
mechanisms
Dead tissue becomes antigenicFAB F
activation of complement Fimmune response
Cell Injurv:
Recommendation :
!n some cases , high oxygen therapy to
improve hypoxia is !OT given because it
generates oxygen derived FREE RAD!CALS
( Reactive Oxygen Species ROS)
Cell Injurv:
2· Free Radicals
Free radicals are chemical species with a
single unpaired electron in an outer orbital,
they are chemically unstable and therefore
readily react with other molecules, resulting in
chemical damage.
To gain stability, the radical gives up or steals
an electron.
Radicals can bind to proteins, carbohydrates
lipids, producing damage.
Cell Injurv:
S6urces 6 Free Radicals in 7ath6l6gy
Chemical injury
Physical injury
!nflammation
Oxygen toxicity
Reperfusion injury
Nalignant transformation
Aging
Cell Injurv:
F6rmati6n 6 Free Radicals :
End6gen6us r6m n6rmal metab6lism
Reduction Oxidation reaction (REDOX) in
mitochondria
Transition metals (Copper, !ron) catalyze
Free Radicals formation by donating or
accepting free electrons
(Fenton reaction)
Ferric iron Ferrous iron
su7er6ide
Cell Injurv:
E6gen6us 6rmati6n :
!onizing radiation
Drug metabolism
Cell Injurv:
Free Radicals (Eam7les)
Reactive Oxygen Species (ROS) generated
by mitochondrial respiration :
Oxygen Superoxide
H
2
O
2
(Hydrogen peroxide)
OH (hydroxyl group)
!nflammation :
Accumulation of leucocytes
!O (!itric oxide)F reactive nitrite
Cell Injurv:
Nechanism 6 injury by Free Radicals
Lipid peroxidation
(oxidative degradation of lipids):
Destruction of unsaturated fatty acids
by binding to methylene groups (CH2)
that posses reactive hydrogen
molecules
Cell Injurv:
2Protein destruction:
By cross linking proteins forming disulfide
bonds (SS) inactivate enzymes, S
polypeptide degradation
D!A alteration:
By producing single strand breaks in D!A
!nduce mutation that interfere with cell
growth
Cell Injurv:
!nactivati6n Free Radicals
Spontaneous decay
Enzymes
Superoxide dismutase,
glutathione peroxidase, and catalase
Antioxidants
Block synthesis or inactivate free radicals
!nclude vitamin E, vitamin C, albumin,
ceruloplasmin, and transferrin
Cell Injurv:
3· Chemical Agents
Chemical agents can cause cellular injury
by:
direct contact of the chemical with
molecular components of the cell.
!ndirect injury
formation of free radicals, or lipid
peroxidation.
Cell Injurv:
Examples of injurious chemicals
Cyanide disrupts cytochrome oxidase.
Nercuric chloride binds to cell
membrane in cell resulting in increased
permeability.
Chemotherapeutic agents S antibiotics
may act in the same way.
Carbon Nonoxide (CO)
Ethanol
Lead
Cell Injurv:
Action of Carbon Nonoxide :
Has a very high affinity to hemoglobin
(carboxyhemoglobin: COHb)
The effect of large quantities of COHb is
death (carbon monoxide poisoning).
Smaller quantities of COHb leads to
tiredness,dizziness S unconsciousness.
Cell Injurv:
Action of Ethanol :
The conversion of ethanol to acetaldehyde
leads to formation of free radical.
Acetaldehyde initiates changes in liver
Fatty change
Liver enlargement
Liver cell necrosis.
Cell Injurv:
liver enlargement with deposition of fat
Cell Injurv:
Action of Lead :
Nimics other metals (calcium, iron and zinc)
which act as cofactors in many catalyzing
enzymatic reactions.
Acts on the C!S by interfering with
neurotransmitters, blocking glutamate
receptor.
(Nay cause wrist, finger,Sfoot paralysis).
Affects hemoglobin synthesis
Cell Injurv:
!ndirect injury of some chemicals :
Activation in the liver by the P mixed function
oxidases in SER .
CCL F CCL (FR) F membrane
phospholipid peroxidation S ER destruction:
protein lipid F !o apoproteins for lipid
transport F Fatty liver
Nitochondrial injury F ATP F Failure of
cell function F increased cytosolic Ca
+
F
cell death
Acetaminophen may act similarly
Cell Injurv:
4· Physical agents
Nechanical injury resulting in tearing, or
crushing of tissues.
e.g.: blunt injuries , car accidents..
!onizing Radiation
Water and D!A are the most vulnerable
target
Cell Injurv:
Physical agents (c6nt..)
Extreme temperatures
Hypothermia
Hyperthermia
Atmospheric Pressure
Blast injuries
Water pressure - increased or decreased
Cell Injurv:
S·!necti6us Agents
Bacteria: produce toxins
Endotoxin
Exotoxin
viruses :
Decrease the ability to synthesize proteins
Change host cell's antigenic properties
Cell Injurv:
S·!mmun6l6gical reacti6ns
Cell membranes are injured by contact
with immune components such as
lymphocytes, macrophages..etc
Exposure to these agents causes changes
in membrane permeability
Cell Injurv:
6· Cenetic Diseases
Cenetics play a substantial role in cellular
structure and function.
A genetic disorder can cause a dramatic
change in the cell's shape, structure,
receptors, or transport mechanisms.eg :
Enzyme deficiencies
Sickle Cell Anemia
Cell Injurv:
7· Nutriti6nal !mbalances
Adequate amounts of proteins, lipids,
carbohydrates are required.
Low levels of plasma proteins, like
albumin, encourages movement of water
into the tissues, thereby causing edema.
Hyperglycemia, hypoglycemia,
vitamin deficiencies (vitamins E, D, K, A,
and folic acid)
Excess food intake is also classified as a
nutritional imbalance
Cell Injurv:
Nechanism 6 cell injury S
sites 6 damage
Cell Injurv:
Function is lost before morphological
changes occur
EN changes
Nicroscopic changes
Cross changes
Ceneral Considerations:
Cell Injurv:
Result of injury depends on :
!njury : Type
Duration
Severity
Type of cell:
Specialization
Adequacy of blood supply, hormones,
nutrients
Regenerative ability or adaptability
Cenetic make up
Cell Injurv:
Ste7s S Cellular targets in !njury :
Cell Injurv:
1· Nit6ch6ndria:
!nterruption of oxidative metabolism
Loss of energy due to formation of
mitochondrial permeability transition
pore (NPT) F loss of membrane
potential F prevents ATP generation
(ATP depletion)
Cytochrome c released into cytosol F
activates apoptosis.
O2 depletion F ROS
Cell Injurv:
2· Cell Nembranes
!mportant sites of damage :
Nitochondrial membraneFG ATP
Plasma membraneF failure of !a pump
leads to cellular amounts of water
Lysosomal membrane F enzyme release,
activation S digestion of cell components
Cell Injurv:
3· !nlu 6 Calcium:
Ca stability is maintained by ATP
Loss of Ca homeostasis F cytosolic Ca
+
F activation of:
phospholipases
proteases
ATPases
Endonucleases
Cell Injurv:
4·Pr6tein synthesis:
High fluid levels cause ribosomes to
separate from the swollen endoplasmic
reticulum F Gprotein synthesis,
glycolysis
Netabolic acidosis
S· Cenetic a77aratus
D!A defects S mutations
Cell Injurv:
!njury at one locus leads to wide
ranging secondary effects
Cascading effect
Cell Injurv:
Subcellular res76nse t6 injury
Cell Injurv:
Hypertrophy of Smooth Endoplasmic
Reticulum in liver induced by some drugs
e.g. barbiturates , alcohol.. etc.
2Nitochondrial alterations in size S number
e.g. in atrophy, hypertrophy, alcoholic
liver
Cytoskeletal abnormalities
e.g. microtubule abnormality involved
in cell mobility
Cell Injurv:
Lysosomal Catabolism:
Enzymatic digestion of foreign material
(Heter67hagy / 7in6cyt6sis S 7hag6cyt6sis)
or intracellular material (Aut67hagy).
Persistent debris residual body
(Undigestible lipid peroxidation products
Li76uscin 7igment.
Cell Injurv:
Norphology of reversible cell injury:
Ultrastructurally :
- Ceneralized swelling of the cell and its
organelles
- Blebbing of the plasma membrane
- Detachment of ribosomes from the
endoplasmic reticulum
- Clumping of nuclear chromatin.
Cell Injurv:
Transition to irreversible cell injury :
- !ncreasing swelling of the cell
- Swelling and disruption of lysosomes
- Severe swelling S dysfunction of mitochondria
with presence of large calcium rich densities
in swollen mitochondria
- Disruption membranes phospholipase
- !rreversible nuclear changes
Ultra structural changes in irreversible injury
mitochondria
Breaks in cell & organelles membranes
Nucleus
Cell membrane
Endoplastic retic
lysosomes
Amorphous density.bizarre forms.
calcification
rupture
fragmentation
See by light mic
!uclear changes in irreversible changes
by light microscopy
!yknosis
Nuclear shrinkage¹Increased
basophilia
!yknotic nucleus
karyolysis
karyorrhexis
Anucleated cell
Cell Injurv:
After death
Cellular constituents are digested by lysosomal
hydrolases enzymes S proteins leak into
extracellular space useful in diagnosis
Nyocardial !nfarction ( creatine kinase S
troponins)
Liver injury (biliary obstruction): Alkaline
phosphatase
Dead cells converted to phospholipid masses
(Nyelin Figures) Phagocytosis or degraded to
fatty acids calcification
Summary
Cell Injurv:
!F !N]URED CELLS DON'' D!E, 'HE
NA ADAP' 'O PRO'EC' 'HENSELvES !
Cell Injurv:
Cellular Ada7tati6ns
Cells change to
Adapt to a new environment
Escape from injury
Protect themselves
Cell Injurv:
Cellular Ada7tati6ns:
Crowth adaptations:
Hyperplasia, Hypoplasia,
Hypertrophy, Atrophy,
Netaplasia , Dysplasia.
Degenerations: (Accumulations)
Hydropic change (water collection in cell /edema)
Fatty Change
Hyaline Change
Pigment storage - wear S tear..
Cell Injurv:
Cellular Ada7tati6n t6 !njury
The most common morphologically
apparent adaptive changes are
- Atrophy (decrease in cell size)
- Hypertrophy (increase in cell size)
- Hyperplasia (increase in cell number)
- Netaplasia (change in cell type)
Cell Injurv:
Atr67hy
Decrease in cell size due to loss of cell substance
(protein degradation S lysosomal proteases digest
extracellular endocytosed molecules )
Often hormone dependent (insulin, TSH, etc.).
Atrophic cells have diminished function.
Cell Injurv:
Atr67hy
Physiologic:
Uterus following parturition
Pathologic:
Decreased workload (Disuse atrophy)
Loss of innervation (Denervation atrophy)
Decreased blood supply (Brain atrophy)
Nalnutrition (Narasmus).
Lack of hormonal stimulation.
Ageing:
Senile atrophy
Cell Injurv:
Disuse atr67hy 6 muscle ibers
Cell Injurv:
Atr67hy 6 r6ntal l6be
Cell Injurv:
Atr67hy: Undescended testes
Cell Injurv:
Hy7ertr67hy
Hypertrophy is an increase in cell size by gain of
cellular substance
With the involvement of a sufficient number of
cells, an entire organ can become hypertrophic
Hypertrophy is caused either by increased
functional demand or by specific endocrine
stimulations
With increasing demand, hypertrophy can reach a
limit beyond which degenerative changes and
organ failure can occur
Cell Injurv:
Hy7ertr67hy
Physiological S Pathological
Skeletal muscles in manual workers S
athletes
Smooth muscles in pregnant uterus
(Hyperplasia accompanies hypertrophy here)
Cardiac muscles in hypertension
Remaining kidney after nephrectomy
Cell Injurv:
Let ventricle hy7ertr67hy · HP'N
C6m7are n6rmal S 7regnant uterus
Cell Injurv:
Hy7er7lasia
Hyperplasia is an increase in the number of
cells of a tissue or organ, from an increased
rate of cell division.
!f cells have mitotic ability and can
synthesize D!A, both hyperplasia and
hypertrophy can occur.
Hyperplasia may be a predisposing condition
to neoplasia
Cell Injurv:
Cells dier in their ca7acity t6 divide :
High capacity: Epidermis, intestinal
epithelium hepatocytes, bone marrow,
fibroblasts.
Low capacity: Bone cartilage, smooth
muscles
!il capacity: !eurons, cardiac muscle,
skeletal muscle..
Cell Injurv:
'y7es 6 Hy7er7lasia
Physi6l6gical Hy7er7lasia
(hormonal or compensatory), Examples:
Uterine enlargement during pregnancy
Female breast in puberty S lactation
Compensatory hyperplasia in the liver
Cell Injurv:
Path6l6gical
Hyperplasia of the endometrium
(excessive hormone stimulation).
Wound healing
(Effects of growth factors).
!nfection by papillomavirus
Cell Injurv:
End6metrial Hy7er7lasia
Cell Injurv:
Neta7lasia
Netaplasia is a ¨reversible" change
(adaptation ) in which one adult cell type
is replaced by another adult cell type that
are better suited to tolerate a specific
abnormal environment.
Nay occur in epithelial or mesenchymal
tissue. e.g. Bronchial , gastric, S cervical
epith., and bone in injured soft tissue
Cell Injurv:
Some disadvantages occur :
Because of metaplasia, normal protective
mechanisms may be lost.
Persistence of signals that result in
metaplasia often lead to progression from
metaplasia to dysplasia and possibly to
adenocarcinoma.
Cell Injurv:
Eam7le 6 Neta7lasia
Replacement of ciliated columnar
epithelium with stratified squamous
epithelium in respiratory tract of a smoker.
Cell Injurv:
C6lumnar (gastric) meta7lasia in
es67hageal squam6us e7ithelium
Cell Injurv:
Dys7lasia
Abnormal changes in size, shape,
appearance, and organizational structure
of the cells
Sometimes atypical hyperplasia can
progress to neoplasia
Caused by persistent injury or irritation
Cervix, oral cavity, gallbladder, and
respiratory tract
¨Cells having dis6rdered arrangement"
Cell Injurv:
Cervical dys7lasia
Cell Injurv:
!ntracellular Accumulati6ns
S De76sits
Cell Injurv:
Nay 6ccur in any 6ne 6 the
6ll6wing ways :
Excessive production of a normal product
but metabolic function is inadequate
!ormal or abnormal substance
accumulates but there is genetic or
acquired defective enzyme mechanism for
removal
Abnormal exogenous substance
accumulates because the cell does not
possess a mechanism for removal
Cell Injurv:
Accumulati6ns include
Water
( Hydropic degeneration/cloudy swelling)
Fatty change
Cholestrol S cholestrol esters
Proteins
Clycogen
Pigments
Calcium
Amyloid deposition
Cell Injurv:
Hydropic degeneration
Cell Injurv:
1· Fatty change
Accumulation of excessive lipid in cells
The liver is the main organ involved, to
lesser extent heart and kidney
Fatty acids hepatocytes triglyceride
+ apoproteins lipoprotein exit liver
Excess accumulation may result from
defect in any of the above steps
Cell Injurv:
Causes 6 atty change :
Toxins including alcohol
Starvation and protein malnutrition
Diabetes mellitus
Oxygen lack (anemia S ischemia )
Drugs, Complicate pregnancy S Obesity
Cell Injurv:
N6r7h6l6gy 6 atty liver
Cross appearance in liver depends on
severity
!ormal to large size, looks yellow and greasy
when severe
Histology
Fat accumulates in hepatocytes as small
vacuoles in cytoplasm with nucleus in the
center (Nicr6vesicular atty change ).
The whole cytoplasm is replaced by fat and
nucleus is pushed to one side of the cell
(Nacr6vesicular atty change).
Cell Injurv:
Fatty Liver (Alcoholism)
Cell Injurv:
2· Ch6lestr6l S Ch6lestr6l esters
Accumulate in macrophages ( foam cells )
S in foreign body giant cells :
Atherosclerosis
Hereditary S Acquired hyperlipidemia
Xanthomas (a yellow nodule or plaque,
especially of the skin, composed of lipid
laden histiocytes).
Cell Injurv:
3· Pr6tein accumulati6n:
kidney in the nephrotic syndrome.
Plasma cells as immunoglobulins.
Nallory Bodies: Alcoholic liver disease as
(Eosinophilic intracellular hyaline body)
Clycogen accumulation in Clycogen
Storage Diseases.
Liver Nallory hyaline Alcoholism
Cell Injurv:
4· Path6l6gic Calciicati6n
A Dystrophic calcification :
Abnormal deposition of calcium phosphate
in dead or dying tissue
Dystrophic calcification is an important
component of the pathogenesis of
atherosclerotic disease and valvular heart
disease.
Areas of caseous, coaggulative or fat
necrosis.
Dead parasites S their ova
Cell Injurv:
cont.
B Netastatic calcification :
Calcium deposition in normal tissues as a
consequence of hypercalcemia:
!ncreased PTH with subsequent bone
resorption
Bone destruction: NETASTAT!C BO!E
CA!CERS
vitamin D disorders Renal failure
Organs affected:
Kidney, stomach, lungs..
Cell Injurv:
Dystrophic calcification Stomach.
Cell Injurv:
S·Pigments
Pigments
EXOGENOUS
Hb-derived Non Hb -derived
ENDOGENOUS
Bilirubin
Iron
Tattooing
Anthracosis
Lipofuscin
Melanin
Cell Injurv:
E6gen6us 7igment :
Anthrac6sis :
Accumulation of carbon, black pigment
Smokers
Tatooing
Cell Injurv:
E6gen6us 7igment : Anthrac6sis
Cell Injurv:
End6gen6us 7igments :
1· Nelanin 7igment :
Brown pigment synthesized in melanocytes.
Nelanin protects the nuclei of cells in
basal layer of epidermis against effects of
Uv light
Lesions associated with melanocytes
Noles (nevi)...benign
Nelanoma...malignant
Lesions can occur anywhere
e.g.rectum,eye.
Cell Injurv:
2· Li76uscin 7igment
Brown pigment in cytoplasm of cells,
represents residue of oxidized lipid derived
from digested membranes of organelles.
!t is called ¨wear and tear"pigment
accumulates as a part of the aging process
and atrophy, in which lipid peroxidation
take part in it.
!t is harmless to the cell.
Large amounts in atrophic organs gives
rise to ¨Br6wn atr67hy" e.g brown
atrophy of the heart.
Cell Injurv:
Li76uscin
Cell Injurv:
3· Bile 7igment (Bilirubin )
Derived from heme of Hb from destroyed RBC in
reticuloendothelial system.
Conjugated in hepatocytes with glucuronic acid
and excreted as bile.
Hyperbilirubinemia may present clinically as
jaundice
Causes may be hemolysis, liver diseases or
obstruction to the outflow of bile
Cell Injurv:
4· Ecess ir6n accumulati6n
Total body iron... 2 gm.
Functional pool
Hb, myoglobin, cytochromes S catalase
Storage pool
in macrophages of RES in the ferric form
as ferritin S / or hemosiderin which is
golden brown.
Potasium ferrocyanide + hemosiderin =
ferric ferrocyanide. This is known as "
Prussian Blue reacti6n" 6r Perl`s
reacti6n.
Cell Injurv:
!ron overload: Localized or systemic
Local increase of iron in tissues
Localized hemorrhage in tissues
Chronic venous congestion of lung in heart
failure
Systemic increase of iron
Hemosiderosis ... !ron in RES without much
damage
Occurs in:
Excessive hemolysis
Nultiple blood transfusions
!ntravenous administration of iron
Cell Injurv:
Hemosiderin granules in liver cells.
A HSE section showing goldenbrown, finely
granular pigment.
B Prussian blue reaction, specific for iron.
Cell Injurv:
!di67athic Hem6chr6mat6sis
Abnormality is lack of regulation of iron
absorption S defect in the monocyte
macrophage system.
!ron accumulates in liver, pancreas, other
parenchymal cells S to lesser extent in
RES.
!nduce fibrosis, secondary diabetes,
cirrhosis S liver cancer
Cell Injurv:
S· Amyl6id6sis
Extracellular deposition of an abnormal fibrillar
proteins in various tissues and organs (kidney,
heart, brain, liver.etc.)
The abnormal protein is called Amyl6id.
Nany types associated with different diseases or
primary forms
H S E . Hyalinelike acellular eosinophilic material
Congo red stains amyloid pink or red and under
polarizing microscopy gives apple green
birefringence .
Cell Injurv:
Amyl6id de76siti6n in kidney
Cell Injurv:
C6ng6 Red Stain
Cell Injurv:
Classiicati6n 6 amyl6id6sis
Localized amyloid deposition
larynx,lungs,urinary bladder,etc..
Systemic amyloidosis
multiple myeloma associated .. AL amyloid
Reactive (secondary amyloidosis) .
AA amyloid
RHEUNATO!D ARTHR!T!S,
!!FLANNATORY BOWEL D!SEASE,
OSTEONYEL!T!S,
HODCK!!'S D!SEASE A!D RE!AL CELL
CARC!!ONA.
Hereditary amyloidosis
Cell Injurv:
CELL DEA'H
Cell Injurv:
CELL DEA'H
Ultimate result of injury, following
ischemia, infection, toxins, immune
reactions..
Physiologically seen in embryogenesis,
lymphoid tissue development, hormonally
induced involution.
Therapeutically in cancer radiotherapy and
chemotherapy.
Cell Injurv:
'y7es :
!ecrosis: Norphologic changes seen
in dead cells within living tissue.
Autolysis: Dissolution of dead cells by
the cells own digestive enzymes. (not
seen)
Apoptosis: Programmed cell death.
Physiological, cell regulation.
Cell Injurv:
NECROS!S
!rreversible
!ecrosis is local cell death and cellular
dissolution in living tissues.
!ecrosis involves the process of self/auto
digestion and lysis.
Cell Injurv:
N6r7h6l6gic changes :
!ncreased eosinophilia of cells
Pyknosis of nuclei
Karyorrhexis
Karyolysis: dissolution of the nucleus
from hydrolytic enzymes
Release of catalytic enzymes from
lysosomes cause either autolysis or
heterolysis
Cell Injurv:
Norphologic appearance of necrosis is
due to:
Enzymic digestion of the cell
Denaturation of proteins
Types: coagulative, liquefactive, caseous,
fat necrosis, gummatous necrosis and
fibrinoid necrosis.
Sequels of !ecrosis:
Autolysis
Phagocytosis
Organization S fibrous repair
Dystrophic calcification
Cell Injurv:
1· C6agulative necr6sis
Commonest type of necrosis, usually ischemic
!nfarction specially in heart (Nyocardial
!nfarction) Also in kidney S in adrenals..
variable appearance mostly firm texture.
!t is suspected that high levels of intracellular
calcium plays a role in coagulative necrosis.
Results from denaturation of all proteins
including enzymes .
Cell Injurv:
Hist6l6gy:
Preservation of the tissue architecture S
cellular outlines.
The necrotic area stains more
eosinophilic, often devoid of nuclei.
Cell Injurv:
Renal !narcti6n: C6agulative
Necr6sis
Cell Injurv:
2· Liqueactive Necr6sis
Autolysis predominates and results in liquefied
mass e.g. hypoxia in brain, bacterial infections
(abscess).
Brain cells have a large amount of hydrolytic
digestive enzymes (hydrolases). These
enzymes cause the neural tissue to become
soft and liquefy.
Liquefactive necrosis is what causes pus to
form.
Hydrolytic enzymes are released from neutrophils
to fight an invading pathogen.
E. Coli, Staphylococcus, and Streptococcus
Cell Injurv:
Str6ke· Liquiactive necr6sis
Cell Injurv:
Lung abscess:
Liqueactive
necr6sis
Cell Injurv:
Liver abscess: Liquefactive necrosis
Cell Injurv:
3· Case6us Necr6sis
Crossly ¨cheeselike", appearance, being soft
and white.
Histology:
Central cheesy material , rimmed by chronic
inflammatory cells, epitheloid cells S Langhans
giant cells ( CRA!ULONA)
Typical of tuberculosis, may be seen in others
!s a distinctive form of coagulative necrosis
modified by capsule lipopolysacchride of TB
bacilli
Cell Injurv:
Case6us necr6sis in 'ubercul6sis
Cell Injurv:
Case6us necr6sis · 'ubercul6sis
Cell Injurv:
4· Fat Necr6sis
Two types :
Traumatic fat necrosis foreign body giant
cells calcification hard lump
Enzymatic fat necrosis due to acute
pancreatitis
Acute Pancreatitis :
Nedical emergency
Enzymes released, digests fat
Adipose tissues triglycerides S fatty acids
saponification S calcification
Cell Injurv:
Foci of fat necrosis with saponification
in the mesentery
Cell Injurv:
Fat Necr6sis · Perit6neum.
Cell Injurv:
Cangrene
!ecrosis plus putrefaction (rotting) by saprophytes.
Wet gangrene: Coagulative necrosis due to
ischemia and liquifactive necrosis due to
superimposed infection.
Dry gangrene: Drying of dead tissue, is a form
of coagulative necrosis, applied to necrosis of
the lower limbs distally, associated with
peripheral vascular disease.
!ecrosis is separated by a line of demarcation
from viable tissue.
Cas gangrene: This caused by wound
contamination by anaerobic bacteria (Clostridia
perfringes)
Cell Injurv:
'6es · Dry Cangrene
Cell Injurv:
Wet Cangrene
Am7utated Diabetic 66t
Cell Injurv:
APOP'OS!S
Programmed cell death by suicide
The cell's membrane remains intact
Apoptosis is characterised by death of single
cells or clusters and results in cell shrinkage, not
lysis and swelling without an inflammatory
reaction,
unlike necrosis where there is death of large
amounts of the tissue and there is an
associated inflammatory reaction.
Cell death involved in normal and pathologic
conditions.
Cell Injurv:
APOP'OS!S
Apoptosis depends on cellular signals, these
signals cause protein cleavage (proteases)
within the cell, causing cell death.
Programmed and energy dependent process
designed to switch cell off and eliminate them
Cell shrinkage
Chromatin condensation most characteristic
Formation of cytoplasmic blebs and apoptotic
bodies
Phagocytosis of apoptotic cells or bodies
Cell Injurv:
'w6 main 7athways
!ntrinsic 'mitochondrial' pathway:
!ncreased permeability of mitochondrial
membrane results in release of proapoptotic
factors (cytochrome c and A!F) that activate
downstream caspases F death .
Extrinsic 'death receptor pathway':
FAS and T!F receptor families with death
domain.
Cell Injurv:
Cell Injurv:
Physi6l6gic a767t6sis
During development, embryogenesis.
Homeostatic mechanism to maintain cell
population(Cell turnover in intestinal crypts).
!mmune reaction defense mechanism.
!n aging.
Shedding of menstrual endometrium.
!nvolution of breast after weaning.
Cell Injurv:
Path6l6gic a767t6sis
Prostatic 'atrophy' after castration.
Death of inflammatory cells after inflammation
When cells are damage by disease or injurious
agents
D!A damage e.g. radiation, chemotherapy,
Cytotoxic drugs
viral infections e.g. viral hepatitis
!eoplasia: tumours that regress or
involution
Deletion of autoreactive T cells in thymus
Others including rejection of transplants
Cell Injurv:
A, Apoptosis of epidermal cells in an immunemediated reaction. The
apoptotic cells are visible in the epidermis with intensely eosinophilic
cytoplasm and small, dense nuclei. HSE stain.
B, High power of apoptotic cell in liver in immunemediated hepatic cell
injury.
Cell Injurv:
Comparison of apoptosis with necrosis
Apoptosis
Active process
Occur in single cells
Physiological S
pathological
!o inflammatory
reaction
!ecrosis
Passive process
Affects mass of
cells
Always pathological
stimulates
!nflammation
Cell Injurv:
Aging and Cellular Death
Theories
Aging is caused by accumulations of injurious
events
Aging is the result of a genetically controlled
developmental program.
Nechanisms
Cenetic, environmental, and behavioral
Changes in regulatory mechanisms
Degenerative alterations
Cell Injurv:
Cellular aging
Cenetic e.g. failure of repair mechanisms , Clock
genes overexpression of antioxidative enzymes
Telomerase activity ...etc
Telomerase activity stops in somatic cells, but
continues in stem cells S germ cells
Environmental: generation of FR, diet
Accumulation of multiple defectsF Aging
Aged cells show Lipofuscin pigment , abnormally
folded proteins S advanced glycosylation end
products ( ACES's)

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