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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Liquefactive necrosis
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Liquefactive necrosis
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Liquefactive necrosis
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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;
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