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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

Cell Injury:


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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

Cell Injury:


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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.

Cell Injury:


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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 .

Cell Injury:


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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:

St k Li if ti i


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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.

Cell Injury:


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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

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