Cell Injury Notes-1

8/11/2019 Cell Injury Notes-1

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Cells are stressed so severely that theyare no longer able to adapt

Exposed to inherently damaging agents.


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Physical agents

Trauma- abrasion, laceration, contusion,

haemorrhage, fracture, crush injuryHyperthermia- heat stroke, heat cramps, heat

exhaustion

Hypothermia- generalized or localized

Changes in atmospheric pressure- Caissondisease

Electric shock- burns / ventricular arrhythmia

Thermal injury- various degrees of burns


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Chemical agents and drugs

Virtually any chemical agent can cause cell

injury. Injury due to poisons (toxic substances-Ar, Cy,

Hg).

Air pollutants,insecticides,CO, asbestos, alcohol.Can cause:Metabolic effects, corrosive effects,mutagenic effects


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One or two general mechanisms:

1. Some chemicals act directly by combiningwith a critical molecular component or cellularorganelle.

2. Many other toxic chemicals are notintrinsically biologically active, must be firstconverted to reactive toxic metabolites, which

then act on target cells.


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Radiation injury

Electro magnetic waves ( X- rays and gamma

rays)High- energy neutrons and charged particles (

alpha and beta particles and protons)

Cause damage to DNA / cell membranes/cytoplasmic alterations/ vascular damage.

Target effect

Indirect effect ( after a latent period )


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Infectious agents

Bacteria, viruses, fungi, parasites,

rickettsiae Insects, snakes, spiders, jelly fish etc.,

Injury is due to-

Intracellular multiplication

Competition for essential nutrients

Production of toxic substancesHypersensitivity reactions


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Intracellular damage

Four intracellular systems are particularly

vulnerable:1. Maintenance of the integrity of cellmembranes

2. Aerobic respiration

3. Protein synthesis

4. Preservation of the integrity of thegenetic apparatus of the cell.


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Common biochemical themes

Important in the mediation of cell injury:

ATP depletion.

Irreversible mitochondrial damage

Intracellular calcium and loss of calciumhomeostasis

Defects in membrane permeability

Oxygen and oxygen-derived free radicals


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Forms and patterns of cell injury

Patterns of reversibleacute cell injury

Patterns of cell death after irreversibleinjury ( necrosis)

Pattern of cell death by suicidecalledapoptosis


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Reversible cell injury

2 patterns: cellular swelling and fatty

change.Cellular swelling: also called hydropic

change or vacuolar degeneration.

Appears whenever cells are incapable ofmaintaining ionic and fluid homeostasis.

First manifestation of almost all forms of cell

injury.When all cells in an organ are affected, there

is pallor, increased weight and increasedturgor.


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Morphology

Small clear vacuoles seen in the

cytoplasmplasma membrane alterations: blebbing,

blunting or distortion of microvilli:

mitochondrial and endoplasmic reticulumdilation

nuclear alterations.


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Fatty change

Occurring in hypoxic injury and variousforms of toxic or metabolic injury

Lipid vacuoles in the cytoplasm.

Principally seen in cells participating in fatmetabolism ( hepatocytes and myocardial

cells).


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Fatty change


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Irreversible cell injury

Accumulation of amorphous, calcium-rich

densities in the mitochondrial matrix.Cell membrane damage is the central factor

Progressive loss of membrane phospholipids,

cytoskeletal abnormalities, toxic oxygen radicals,lipid breakdown products.


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Dead cells

Cytoplasm:

Increased eosinophilia

Glassy homogenous appearance

Nuclear changes-Karyolysis

Pyknosis

Karyorrhexis


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Progression of cell injury


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Apoptosis

Means a falling away form

Programmed cell death.Can be both physiological or pathological.

Usually involves single cells or clusters ofcells - appear as round or oval masseswith intensely eosinophilic cytoplasm.


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Apoptosis


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Necrosis

Refers to a sequence of morphologic changes

that follow cell death in living tissue. This occursin the setting of irreversible exogenous injury.

Types of necrosis are:

Coagulative necrosis

Liquefactive necrosis

Caseous necrosis

Fat necrosisGangrene


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Necrosis

Result of two concurrent processes:

1. Denaturation of proteins.2. Enzymatic digestion of the cell

(autolytic or heterolytic).

Requires hours to develop.

Classic histological picture not apparent

until 4 to 12 hours after irreversible injuryhas occurred.


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Coagulative necrosisWhen denaturation of proteins is the primary

factor Preservation of the basic structural outline of the

coagulated cell or tissue for a span of few days

Affected tissues exhibit a firm texture.

Seen in hypoxic cell death in all tissues exceptbrain

Myocardial Infarction is a prime example:coagulated, anucleate cells may persist forweeks


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Coagulative necrosis

N l h


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Nuclear ghosts


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Liquefactive necrosisCharacteristic of focal bacterial or occasionally

fungal infections

In brain hypoxic death cells invokes this type ofnecrosis

Complete digestion of dead cells

Transformation of tissue into a liquid viscousmass

If initiated by acute inflammation,the material is

frequently creamy yellow because of thepresence of dead white cells and is called pus


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Caseous necrosisDistinctive form of coagulative necrosis.

Seen most often in tuberculous infection.

Caseous- white and cheesy in the area ofnecrosis ( gross).

Histology: necrotic focus appears as granulardebris composed of fragmented, coagulatedcells and enclosed within a distinctiveinflammatory border.

Tissue architecture is completely obliterated.


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Caseous necrosis


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Caseative necrosis


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Gangrenous necrosis

Usually applied to a limb that has lost itblood supply and has undergonecoagulative necrosis.

There is superimposed bacterial infectionand there is liquefactive action of thebacteria and leukocytes ( wet gangrene)


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Gangrene


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Necrosis vs Apoptosis


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p pPathologic (hypoxia, toxins).

Consequence of irreversible

cell injury.

"cell homicide"

Physiologic, genetically

regulated process.

Occasionally pathologic.

"cell suicide"

Many cells affected- Cell swelling, Organelle

disruption, Loss of membrane

integrity.

- Coagulation or liquefaction

Few cells affected.- Cell shrinkage, apoptotic

bodies which are eaten by

macrophages.

Karyorrhexis and karyolysis:

random, diffuse fragmentationand dissolution of the nucleus.

Orderly nuclear

condensation andfragmentation.

Inflammation with injury to

surrounding normal tissues.

No Inflammation or tissue

injury.


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Thank youPathologic Basis of disease Robbins & Cotran, 8th EdGeneral & systemic pathology Underwood, 2nd Ed

Principles of Internal Medicine Harrisons, 15th

EdTextbook of Medical Physiology Guyton, 9th EdAids to Pathology Dixon/ Quirke, 4th EdSurgical Pathology Ackerman, 9th Ed;Lecture notes on Pathology Cotton, 4th Ed;

http://clinicalpathology.wordpress.com/

Cell Injury Notes-1

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