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Cell Injury:
Cellular Injury(year 2010 )
Dr. Huda M.Zahawi, FRC.Path.
90-37
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Cell Injury:
Topic Outline
Causes of cell injury
Types of Injury
Priciples & Mechanisms of cell injury
Outcome : ?Reversible ? Irreversible
Morphology
Adaptation to Injury
Patterns & types of Cell Death
Process of Aging
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Cell Injury:
Cellular Injury & Adaptation
Normal cell is in a steady dynamic stateHomeostasis:
The ability or tendency of an organism orcell to maintain internal equilibrium by
adjusting its physiological processes.
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Cell Injury:
Cells are constantly exposed to stresses.
Normal physiologic stress
Severe stresses: injury results, and altersthe normal steady state of the cell,consequently,
It can survive in a damaged state andadapt to the injury
(reversible injury or adaptation)
It can die
(irreversible injury or cell death).
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NORMAL
CELL
STRESS INJURY
AtrophyHypertophy
Hyperplasia
Metaplasia
Cellular swelling
Vacuolar change
Fatty change
Necrosis
Apoptosiss
Irreversible
injury
Reversible
injury
Adaptation
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Cell Injury:
Causes of Cell Injury
Hypoxia and ischemia
Free radicals
Chemical agents Physical agents
Infections
Immunological reactions Genetic defects
Nutritional defects
Aging
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Cell Injury:
TYPES OF INJURY
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Cell Injury:
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- Hypoxia & Ischemia
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Cell Injury:
Ischemia & Hypoxia induce mitochondrial
damage.
This results in decreasedATP which in
turn reduces energy for all cell functions !
If persistent CELL DEATH
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Cell Injury:
Hypoxia is a common cause of cell injury
Result : Cell resorts to anaerobic glycolysis
Ischemia is the commonest cause ofhypoxia, & injures the cells faster than pure
hypoxia
Why ??
Restoration of blood may lead to recoveryOR Ischemia/ Reperfusion injury
Progressive cell damage
Examples : Myocardial & Cerebral infarction
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Cell Injury:
Ischemia/Reperfusion Injury
Restoration of blood flow influx ofhighlevels of calcium
Reperfusion increases recruitment ofinflammatory cells free radical injury
Damaged mitochondria induce free radicalproduction & compromise antioxidant defense
mechanisms
Dead tissue becomes antigenicAB
activation of complement immune response
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Cell Injury:
Recommendation :
In some cases , high oxygen therapy toimprove hypoxia is NOT given because it
generates oxygen derived FREE RADICALS
( Reactive Oxygen Species ROS)
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Cell Injury:
2- Free Radicals
Free radicals are chemical species with asingle unpaired electron in an outer orbital,
they are chemically unstable and thereforereadily react with other molecules, resulting inchemical damage.
To gain stability, the radical gives up or stealsan electron.
Radicals can bind to proteins, carbohydrateslipids, producing damage.
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Cell Injury:
Sources of Free Radicals in pathology
Chemical injury
Physical injury
Inflammation Oxygen toxicity
Reperfusion injury
Malignant transformationAging
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Cell Injury:
Formation of Free Radicals :
Endogenous from normal metabolism
Reduction Oxidation reaction (REDOX) inmitochondria
Transition metals (Copper, Iron) catalyzeFree Radicals formation by donating oraccepting free electrons
(Fenton reaction)
Ferric iron Ferrous ironsuperoxide
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Cell Injury:
Exogenous formation :
Ionizing radiation
Drug metabolism
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Cell Injury:
Free Radicals (Examples)
Reactive Oxygen Species (ROS) generated
by mitochondrial respiration :
OxygenSuperoxide H2O2 (Hydrogen peroxide)
OH (hydroxyl group)
Inflammation :
Accumulation of leucocytes
NO (Nitric oxide)
reactive nitrite
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Cell Injury:
Mechanism of injury by Free Radicals
1-Lipid peroxidation
(oxidative degradation of lipids):
Destruction of unsaturated fatty acidsby binding to methylene groups (CH2)
that posses reactive hydrogenmolecules
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Cell Injury:
2-Protein destruction:
By cross linking proteins forming disulfidebonds (S-S) inactivate enzymes, &polypeptide degradation
3- DNA alteration:By producing single strand breaks in DNA
Induce mutation that interfere with cell
growth
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Cell Injury:
Inactivation Free Radicals
Spontaneous decay
Enzymes
Superoxide dismutase, glutathione peroxidase, and catalase
Antioxidants
Block synthesis or inactivate free radicals Include Vitamin E, Vitamin C, albumin,ceruloplasmin, and transferrin
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Cell Injury:
3- Chemical Agents
Chemical agents can cause cellular injuryby:
direct contact of the chemical withmolecular components of the cell.
Indirect injury
formation of free radicals, or lipidperoxidation.
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Cell Injury:
Examples of injurious chemicals
Cyanide disrupts cytochrome oxidase.
Mercuric chloride binds to cellmembrane in cell resulting in increasedpermeability.
Chemotherapeutic agents & antibioticsmay act in the same way.
Carbon Monoxide (CO)
Ethanol
Lead
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Cell Injury:
Action of Carbon Monoxide :
Has a very high affinity to hemoglobin(carboxyhemoglobin: COHb)
The effect of large quantities of COHb isdeath (carbon monoxide poisoning).
Smaller quantities of COHb leads to
tiredness,dizziness & unconsciousness.
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Cell Injury:
Action of Ethanol :
The conversion of ethanol to acetaldehydeleads to formation of free radical.
Acetaldehyde initiates changes in liver Fatty change
Liver enlargement
Liver cell necrosis.
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Cell Injury:
liver enlargement with deposition of fat
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Cell Injury:
Action of Lead :
Mimics other metals (calcium, iron and zinc)which act as cofactors in many catalyzing
enzymatic reactions.Acts on the CNS by interfering with
neurotransmitters, blocking glutamate
receptor.(May cause wrist, finger,&foot paralysis).
Affects hemoglobin synthesis
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Cell Injury:
Indirect injury of some chemicals :
Activation in the liver by the P- 450 mixed functionoxidases in SER .
CCL4 CCL3 (FR) membrane
phospholipid peroxidation & ER destruction: protein lipid No apoproteins for lipid
transport Fatty liver
Mitochondrial injury ATP Failure ofcell function increased cytosolic Ca+cell death
Acetaminophen may act similarly
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Cell Injury:
4- Physical agents
Mechanical injury resulting in tearing, orcrushing of tissues.
e.g.: blunt injuries , car accidents.
Ionizing Radiation
Water and DNA are the most vulnerabletarget
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Cell Injury:
Physical agents (cont)
Extreme temperatures Hypothermia Hyperthermia
Atmospheric Pressure Blast injuries
Water pressure increased or decreased
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Cell Injury:
5-Infectious Agents
Bacteria: produce toxins
Endotoxin
Exotoxin
Viruses :
Decrease the ability to synthesize proteins
Change host cells antigenic properties
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Cell Injury:
5-Immunological reactions
Cell membranes are injured by contactwith immune components such aslymphocytes, macrophages.etc
Exposure to these agents causes changesin membrane permeability
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Cell Injury:
6- Genetic Diseases
Genetics play a substantial role in cellularstructure and function.
A genetic disorder can cause a dramaticchange in the cells shape, structure,receptors, or transport mechanisms.eg :
Enzyme deficiencies
Sickle Cell Anemia
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Cell Injury:
7- Nutritional Imbalances
Adequate amounts of proteins, lipids,carbohydrates are required.
Low levels of plasma proteins, like
albumin, encourages movement of waterinto the tissues, thereby causing edema.
Hyperglycemia, hypoglycemia,
Vitamin deficiencies (vitamins E, D, K, A,and folic acid)
Excess food intake is also classified as anutritional imbalance
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Cell Injury:
Mechanism of cell injury &sites of damage
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Cell Injury:
Function is lost before morphologicalchanges occur
EM changes
Microscopic changes
Gross changes
General Considerations:
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Cell Injury:
Result of injury depends on :
Injury : Type
Duration
Severity Type of cell:
Specialization
Adequacy of blood supply, hormones,nutrients
Regenerative ability or adaptability
Genetic make up
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Cell Injury:
Steps & Cellular targets in Injury :
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Cell Injury:
1- Mitochondria:
Interruption of oxidative metabolism
Loss of energy due to formation ofmitochondrial permeability transition
pore (MPT) loss of membranepotential prevents ATP generation(ATP depletion)
Cytochrome c released into cytosol activates apoptosis.
O2 depletion ROS
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Cell Injury:
2- Cell Membranes
Important sites of damage :
Mitochondrial membrane ATP
Plasma membrane failure of Na pumpleads to cellular amounts of water
Lysosomal membrane enzyme release,
activation & digestion of cell components
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Cell Injury:
3- Influx of Calcium:
Ca stability is maintained by ATP
Loss of Ca homeostasis cytosolic Ca+
activation of:
phospholipases
proteases
ATPases
Endonucleases
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C ll I j
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Cell Injury:
4-Protein synthesis:
High fluid levels cause ribosomes to
separate from the swollen endoplasmic
reticulum protein synthesis,
glycolysis
Metabolic acidosis
5- Genetic apparatus
DNA defects & mutations
C ll I j
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Cell Injury:
Injury at one locus leads to wide
ranging secondary effects
Cascading effect
C ll I j
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Cell Injury:
Subcellular response to injury
C ll I j
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Cell Injury:
1- Hypertrophy of Smooth EndoplasmicReticulum in liver induced by some drugs
e.g. barbiturates , alcohol. etc.
2-Mitochondrial alterations in size & number
e.g. in atrophy, hypertrophy, alcoholicliver
3-Cytoskeletal abnormalities
e.g. microtubule abnormality involved
in cell mobility
C ll I j
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Cell Injury:
4- Lysosomal Catabolism:
Enzymatic digestion of foreign material
(Heterophagy / pinocytosis &phagocytosis)orintracellular material (Autophagy).
Persistent debris residual body(Undigestible lipid peroxidation productsLipofuscin pigment.
C ll I j
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Cell Injury:
Morphology of reversible cell injury:
Ultrastructurally : Generalized swelling of the cell and its
organelles Blebbing of the plasma membrane Detachment of ribosomes from the
endoplasmic reticulum Clumping of nuclear chromatin.
Cell Injury:
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Cell Injury:
Transition to irreversible cell injury :
Increasing swelling of the cell Swelling and disruption of lysosomes Severe swelling & dysfunction of mitochondria
with presence of large calcium rich densitiesin swollen mitochondria
Disruption membranes
phospholipase Irreversible nuclear changes
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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
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Nuclear changes in irreversible changesby light microscopy
Pyknosis
Nuclear shrinkage+Increased
basophilia
Pyknotic nucleus
karyolysis karyorrhexis
Anucleated cell
Cell Injury:
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Cell Injury:
After death
Cellular constituents are digested by lysosomal
hydrolases enzymes & proteins leak intoextracellular space useful in diagnosis
Myocardial Infarction ( creatine kinase &troponins)
Liver injury (biliary obstruction):Alkalinephosphatase
Dead cells converted to phospholipid masses
(Myelin Figures) Phagocytosis or degraded to
fatty acids calcification
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Summary
Cell Injury:
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Cell Injury:
IF INJURED CELLS DONT DIE, THEY
MAY ADAPT TO PROTECT THEMSELVES !
Cell Injury:
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Cell Injury:
Cellular Adaptations
Cells change to
Adapt to a new environment
Escape from injury Protect themselves
Cell Injury:
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Cell Injury:
Cellular Adaptations:
Growth adaptations: Hyperplasia, Hypoplasia,
Hypertrophy, Atrophy,
Metaplasia , Dysplasia.
Degenerations: (Accumulations)
Hydropic change (water collection in cell /edema) Fatty Change
Hyaline Change
Pigment storage wear & tear..
Cell Injury:
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Cell Injury:
Cellular Adaptation to Injury
The most common morphologicallyapparent adaptive changes are
Atrophy(decrease in cell size)
Hypertrophy(increase in cell size)
Hyperplasia(increase in cell number)Metaplasia(change in cell type)
Cell Injury:
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Cell Injury:
Atrophy
Decrease in cell sizedue to loss of cell substance
(protein degradation & lysosomal proteases digest
extracellular endocytosed molecules )
Often hormone dependent (insulin, TSH, etc).
Atrophic cells have diminished function.
Cell Injury:
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Cell Injury:
Atrophy
Physiologic:Uterus following parturition
Pathologic: Decreased workload (Disuse atrophy) Loss of innervation (Denervation atrophy)
Decreased blood supply (Brain atrophy)
Malnutrition (Marasmus). Lack of hormonal stimulation.
Ageing: Senile atrophy
Cell Injury:
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Cell Injury:
Disuse atrophy of muscle fibers
Cell Injury:
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C j y
Atrophy of frontal lobe
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Cell Injury:
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j y
Hypertrophy
Hypertrophy is an increase in cell size by gain ofcellular 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 endocrinestimulations
With increasing demand, hypertrophy can reach alimit beyond which degenerative changes andorgan failure can occur
Cell Injury:
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j y
Hypertrophy
Physiological & Pathological
Skeletal muscles in manual workers &athletes
Smooth muscles in pregnant uterus
(Hyperplasia accompanies hypertrophy here) Cardiac muscles in hypertension
Remaining kidney after nephrectomy
Cell Injury:
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j y
Left ventricle hypertrophy - HPTN
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Compare normal & pregnant uterus
Cell Injury:
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Hyperplasia
Hyperplasia is an increase in the number ofcells of a tissue or organ, from an increased
rate of cell division. If cells have mitotic ability and can
synthesize DNA, both hyperplasia and
hypertrophy can occur. Hyperplasia may be a predisposing condition
to neoplasia
Cell Injury:
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Cells differ in their capacity to divide :
High capacity: Epidermis, intestinalepithelium hepatocytes, bone marrow,
fibroblasts.
Low capacity: Bone cartilage, smooth
muscles
Nil capacity: Neurons, cardiac muscle,
skeletal muscle.
Cell Injury:
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Types of Hyperplasia
Physiological Hyperplasia
(hormonal or compensatory), Examples:
Uterine enlargement during pregnancy
Female breast in puberty & lactation
Compensatory hyperplasia in the liver
Cell Injury:
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Pathological
Hyperplasia of the endometrium(excessive hormone stimulation).
Wound healing
(Effects of growth factors). Infection by papillomavirus
Cell Injury:
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Endometrial Hyperplasia
Cell Injury:
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Metaplasia
Metaplasia is a reversible change(adaptation ) in which one adult cell typeis replaced by another adult cell type that
are better suited to tolerate a specificabnormal environment.
May occur in epithelial or mesenchymaltissue. e.g. Bronchial , gastric, & cervicalepith., and bone in injured soft tissue
Cell Injury:
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Some disadvantages occur :
Because of metaplasia, normal protectivemechanisms may be lost.
Persistence of signals that result inmetaplasia often lead to progression frommetaplasia to dysplasia and possibly to
adenocarcinoma.
Cell Injury:
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Example of Metaplasia
Replacement of ciliated columnarepithelium with stratified squamousepithelium in respiratory tract of a smoker.
Cell Injury:
Columnar (gastric) metaplasia in
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Columnar (gastric) metaplasia inesophageal squamous epithelium
Cell Injury:
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Dysplasia
Abnormal changes in size, shape,appearance, and organizational structureof the cells
Sometimes atypical hyperplasia canprogress to neoplasia
Caused by persistent injury or irritation
Cervix, oral cavity, gallbladder, andrespiratory tract
Cells having disordered arrangement
Cell Injury:
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Cervical dysplasia
Cell Injury:
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Intracellular Accumulations& Deposits
Cell Injury:May occur in any one of the
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May occur in any one of thefollowing ways :
Excessive production of a normal productbut metabolic function is inadequate
Normal or abnormal substanceaccumulates but there is genetic oracquired defective enzyme mechanism forremoval
Abnormal exogenous substanceaccumulates because the cell does not
possess a mechanism for removal Cell Injury:
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Accumulations include
Water
( Hydropic degeneration/cloudy swelling)
Fatty change
Cholestrol & cholestrol esters
Proteins
Glycogen Pigments
Calcium
Amyloid deposition Cell Injury:
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Hydropic degeneration
Cell Injury:
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1- Fatty change
Accumulation of excessive lipid in cells
The liver is the main organ involved, tolesser extent heart and kidney
Fatty acids hepatocytes triglyceride
+ apoproteins lipoprotein exit liver
Excess accumulation may result fromdefect in any of the above steps
Cell Injury:
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Causes of fatty change :
Toxins including alcohol
Starvation and protein malnutrition
Diabetes mellitus
Oxygen lack (anemia & ischemia )
Drugs, Complicate pregnancy & Obesity
Cell Injury:
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Morphology of fatty liver
Gross appearance in liver depends onseverity Normal to large size, looks yellow and greasy
when severe
Histology Fat accumulates in hepatocytes as small
vacuoles in cytoplasm with nucleus in the
center (Microvesicular fattychange). The whole cytoplasm is replaced by fat and
nucleus is pushed to one side of the cell(Macrovesicular fattychange).
Cell Injury:
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Fatty Liver (Alcoholism)
Cell Injury:
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2- Cholestrol & Cholestrol esters
Accumulate in macrophages ( foam cells )& in foreign body giant cells :
Atherosclerosis Hereditary & Acquired hyperlipidemia
Xanthomas (a yellow nodule or plaque,especially of the skin, composed of lipid-
laden histiocytes).
Cell Injury:
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3- Protein accumulation:
kidney in the nephrotic syndrome.
Plasma cells as immunoglobulins.
Mallory Bodies: Alcoholic liver disease as(Eosinophilic intracellular hyaline body)
Glycogen accumulation in GlycogenStorage Diseases.
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Liver - Mallory hyaline - Alcoholism
Cell Injury:
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4- Pathologic Calcification
A- Dystrophic calcification :
Abnormal deposition of calcium phosphatein dead or dying tissue
Dystrophic calcification is an importantcomponent of the pathogenesis ofatherosclerotic disease and valvular heart
disease.Areas of caseous, coaggulative or fat
necrosis.
Dead arasites & their ova Cell Injury:
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cont
B- Metastatic calcification :Calcium deposition in normal tissues as aconsequence of hypercalcemia:
Increased PTH with subsequent boneresorption
Bone destruction: METASTATIC BONE
CANCERSVitamin D disorders Renal failure
Organs affected:
Kidne stomach lun s.
Cell Injury:
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Dystrophic calcification - Stomach.
Cell Injury:
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5-Pigments
Pigments
EXOGENOUS
Hb-derived Non Hb -derived
ENDOGENOUS
Bilirubin
IronTattooing
Anthracosis
Lipofuscin
Melanin
Cell Injury:
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Exogenous pigment :
Anthracosis :
Accumulation of carbon, black pigment
Smokers
Tatooing
Cell Injury:
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Exogenous pigment : Anthracosis
Cell Injury:
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Endogenous pigments :
1- Melanin pigment :Brown pigment synthesized in melanocytes.
Melanin protects the nuclei of cells in
basal layer of epidermis against effects ofUV light
Lesions associated with melanocytes
Moles (nevi)..benign Melanoma.malignant
Lesions can occur anywheree.g.rectum,eye.
Cell Injury:
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2- Lipofuscin pigment
Brown pigment in cytoplasm of cells,represents residue of oxidized lipid derivedfrom digested membranes of organelles.
It is called wear and tearpigmentaccumulates as a part of the aging processand atrophy, in which lipid peroxidationtake part in it.
It is harmless to the cell. Large amounts in atrophic organs gives
rise to Brown atrophy e.g brown
atrophy of the heart. Cell Injury:
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Lipofuscin
Cell Injury:
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3- Bile pigment (Bilirubin )
Derived from heme of Hb from destroyed RBC inreticuloendothelial 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 Injury:
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4- Excess iron accumulation
Total body iron.. 2 - 4gm. Functional pool
Hb, myoglobin, cytochromes & catalase
Storage pool in macrophages of RES in the ferric form
as ferritin & / or hemosiderin which is
golden brown. Potasium ferrocyanide + hemosiderin =
ferric ferrocyanide. This is known as Prussian Blue reaction or Perl`s
Cell Injury:
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Iron 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 .. Iron in RES without muchdamage
Occurs in: Excessive hemolysis
Multiple blood transfusions
Intravenous administration of iron
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Hemosiderin granules in liver cells.
A- H&E section showing golden-brown, finelygranular pigment.B- Prussian blue reaction, specific for iron.
Cell Injury:
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Idiopathic Hemochromatosis
Abnormality is lack of regulation of ironabsorption & defect in the monocyte -macrophage system.
Iron accumulates in liver, pancreas, otherparenchymal cells & to lesser extent inRES.
Induce fibrosis, secondary diabetes,cirrhosis & liver cancer
Cell Injury:
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5- Amyloidosis
Extracellular deposition of an abnormal fibrillarproteins in various tissues and organs (kidney,heart, brain, liveretc.)
The abnormal protein is calledAmyloid. Many types associated with different diseases or
primary forms
H & E Hyaline-like acellular eosinophilic material
Congo red stains amyloid pink or red and underpolarizing microscopy gives apple greenbirefringence .
Cell Injury:
l id d i i i kid
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Amyloid deposition in kidney
Cell Injury:
C d S i
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Congo Red Stain
Cell Injury:
Cl ifi i f l id i
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Classification of amyloidosis
Localized amyloid deposition larynx,lungs,urinary bladder,etc..
Systemic amyloidosis multiple myeloma associated .AL amyloid Reactive (secondary amyloidosis) AA amyloid
RHEUMATOID ARTHRITIS, INFLAMMATORY BOWEL DISEASE, OSTEOMYELITIS, HODGKINS DISEASE AND RENAL CELL
CARCINOMA. Hereditary amyloidosis
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CELL DEATH
Cell Injury:
CELL DEATH
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CELL DEATH
Ultimate result of injury, followingischemia, infection, toxins, immunereactions
Physiologically seen in embryogenesis,lymphoid tissue development, hormonally
induced involution.
Therapeutically in cancer radiotherapy and
chemothera Cell Injury:
T
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Types :
Necrosis: Morphologic changes seenin dead cells within living tissue.
Autolysis: Dissolution of dead cells bythe cells own digestive enzymes. (notseen)
Apoptosis: Programmed cell death.Physiological, cell regulation.
Cell Injury:
NECROSIS
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NECROSIS
Irreversible
Necrosis is local cell death and cellulardissolution in living tissues.
Necrosis involves the process of self/autodigestion and lysis.
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Morphologic changes :
Increased eosinophilia of cells
Pyknosis of nuclei
Karyorrhexis Karyolysis: dissolution of the nucleus
from hydrolytic enzymes
Release of catalytic enzymes fromlysosomes cause either autolysis orheterolysis
Cell Injury:
Morphologic appearance of necrosis is
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p g ppdue to:
Enzymic digestion of the cell Denaturation of proteins
Types: coagulative, liquefactive, caseous,
fat necrosis, gummatous necrosis andfibrinoid necrosis.
Sequels of Necrosis:
Autolysis
Phagocytosis
Organization & fibrous repair
Dystrophic calcification
Cell Injury:
1 Coag lati e nec osis
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1- Coagulative necrosis
Commonest type of necrosis, usually ischemic
Infarction specially in heart (MyocardialInfarction) Also in kidney & in adrenals.
Variable appearance mostly firm texture.
It is suspected that high levels of intracellular
calcium plays a role in coagulative necrosis. Results from denaturation of all proteins
including enzymes .
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Histology:
Preservation of the tissue architecture &
cellular outlines.
The necrotic area stains moreeosinophilic, often devoid of nuclei.
Cell Injury:
Renal Infarction: Coagulative
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Necrosis
Cell Injury:
2 Liquefactive Necrosis
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2- Liquefactive Necrosis
Autolysis predominates and results in liquefiedmass e.g. hypoxia in brain, bacterial infections
(abscess).
Brain cells have a large amount of hydrolyticdigestive enzymes (hydrolases). Theseenzymes cause the neural tissue to becomesoft and liquefy.
Liquefactive necrosis is what causes pus toform.
Hydrolytic enzymes are released from neutrophilsto fight an invading pathogen.
E. Coli, Staphylococcus, and Streptococcus
Cell Injury:
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Stroke- Liquifactive necrosis
Cell Injury:
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Lung abscess:Liquefactivenecrosis
Cell Injury:
Li e abscess Liq efacti e nec osis
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Liver abscess: Liquefactive necrosis
Cell Injury:
3 Caseous Necrosis
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3- Caseous Necrosis
Grossly cheese-like, appearance, being softand white.
Histology:
Central cheesy material , rimmed by chronicinflammatory cells, epitheloid cells & Langhansgiant cells ( GRANULOMA)
Typical of tuberculosis, may be seen in others Is a distinctive form of coagulative necrosis
modified by capsule lipopolysacchride of TB
bacilli Cell Injury:
C i i T b l i
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Caseous necrosis in Tuberculosis
Cell Injury:
Caseous necrosis Tuberculosis
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Caseous necrosis - Tuberculosis
Cell Injury:
4 Fat Necrosis
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4- Fat Necrosis
Two types : Traumatic fat necrosis foreign body giant
cells calcification hard lump
Enzymatic fat necrosis due to acute
pancreatitis Acute Pancreatitis :
Medical emergency
Enzymes released, digests fatAdipose tissues triglycerides & fatty acids saponification & calcification
Cell Injury:
Foci of fat necrosis with saponificationi th t
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in the mesentery
Cell Injury:
Fat Necrosis Peritoneum
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Fat Necrosis - Peritoneum.
Cell Injury:
Gangrene
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Gangrene
Necrosis plus putrefaction (rotting) by saprophytes. Wet gangrene: Coagulative necrosis due to
ischemia and liquifactive necrosis due tosuperimposed infection.
Dry gangrene: Drying of dead tissue, is a formof coagulative necrosis, applied to necrosis ofthe lower limbs distally, associated withperipheral vascular disease.
Necrosis is separated by a line of demarcationfrom viable tissue.
Gas gangrene: This caused by woundcontamination by anaerobic bacteria (Clostridia
perfringes)
Cell Injury:
Toes - Dry Gangrene
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Toes - Dry Gangrene
Cell Injury:
Wet GangreneAmputated Diabetic foot
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Amputated Diabetic foot
Cell Injury:
APOPTOSIS
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APOPTOSIS
Programmed cell death by suicide The cells membrane remains intact
Apoptosis is characterised by death of singlecells or clusters and results in cell shrinkage, not
lysis and swelling without an inflammatoryreaction,
unlike necrosis where there is death of largeamounts of the tissue and there is an
associated inflammatory reaction. Cell death involved in normal and pathologic
conditions.
Cell Injury:
APOPTOSIS
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APOPTOSIS
Apoptosis depends on cellular signals, thesesignals cause protein cleavage (proteases)within the cell, causing cell death.
Programmed and energy dependent processdesigned to switch cell off and eliminate them
Cell shrinkage
Chromatin condensation- most characteristic
Formation of cytoplasmic blebs and apoptoticbodies
Phagocytosis of apoptotic cells or bodies
Cell Injury:
Two main pathways
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Two main pathways
Intrinsicmitochondrialpathway:Increased permeability of mitochondrialmembrane results in release of pro-apoptoticfactors (cytochrome c and AIF) that activate
downstream caspases death .
Extrinsicdeath receptor pathway:
FAS and TNF1 receptor families with deathdomain.
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Cell Injury:
Physiologic apoptosis
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Physiologic apoptosis
During development, embryogenesis.
Homeostatic mechanism to maintain cellpopulation(Cell turnover in intestinal crypts).
Immune reaction - defense mechanism. In aging.
Shedding of menstrual endometrium.
Involution of breast after weaning.
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Cell Injury:
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A, Apoptosis of epidermal cells in an immune-mediated reaction. Theapoptotic cells are visible in the epidermis with intensely eosinophilic
cytoplasm and small, dense nuclei. H&E stain.B, High power of apoptotic cell in liver in immune-mediated hepatic cell
injury.
Cell Injury:
Comparison of apoptosis with necrosis
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ApoptosisActive process
Occur in single cells
Physiological &pathological
No inflammatoryreaction
Necrosis Passive process
Affects mass of
cells
Always pathological
stimulatesInflammation
Cell Injury:
Aging and Cellular Death
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Aging and Cellular Death
TheoriesAging is caused by accumulations of injurious
events
Aging is the result of a genetically controlleddevelopmental program.
Mechanisms
Genetic, environmental, and behavioral
Changes in regulatory mechanisms
Degenerative alterations
Cell Injury:
Cellular aging
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Cellular aging
Genetic e.g. failure of repair mechanisms , Clockgenes overexpression of antioxidative enzymesTelomerase activity .etc
Telomerase activity stops in somatic cells, but
continues in stem cells & germ cells
Environmental: generation of FR, diet
Accumulation of multiple defects Aging
Aged cells show Lipofuscin pigment , abnormallyfolded proteins & advanced glycosylation end