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Cell injury (alteration).Degeneration. Cellular &

extracellular mechanisms of trophics.Causes of development ofdegenerations.Morphogenetic mechanisms.

Classification.

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PLAN:

1. Notion about alteration.

2. Main mechanisms of cell injuries.

3. Morphology of cell injury (reversible &

irreversible injuries).

4. Regulation of metabolism in the

organism. Nature of degenerations.

5. Morphogenesis of degenerations.

6. Classification of degenerations.

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Alteration (from lat. Alteratio

change, modification) is a change of

structure of cell, intercellular

substance, tissues & organs, which isaccompanied by disorder of their

vital functions.

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Causes of Cell Injury and Necrosis

Hypoxia Ischemia

Hypoxemia

Loss of oxygen carrying capacity

Physical agents Chemicals, drugs, toxins

Infections

Immunologic reactions

Genetic abnormalities

Nutritional imbalance

Free radical damage

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Cell injury

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Cell Injury General Mechanisms

Four very interrelated cell systems are

particularly vulnerable to injury:

Membranes (cellular and organellar)

Aerobic respiration

Protein synthesis (enzymes, structural proteins,

etc)

Genetic apparatus (e.g., DNA, RNA)

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Biochemical reactions which are involved in

Cell Injury mechanisms

Oxygen and oxygen-derived free radicals

Loss of calcium homeostasis

ATP depletion

Defects in membrane permeability

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Mechanism of Free Radical Injury

Lipid peroxidation damage to cellular

and organellar membranes

DNA damage due to reactions of freeradicals with thymine

Protein cross-linking and fragmentation due

to oxidative modification of amino acidsand proteins

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The defensive mechanism of free

radicals:

a) Intracellular protective enzymes e.g.

glutathione peroxidase, catalase,

superoxide dismutase.

b) Antioxidants e.g. Vit. E, C.

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Loss of calcium homeostasis

Membrane damage and loss of calciumhomeostasis are most crucial

Some models of cell death suggest that a

massive influx of calcium causes cell

death

Too much cytoplasmic calcium:

Denatures proteins Poisons mitochondria

Inhibits cellular enzymes

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Calcium in cell injury

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KINDS OF CELL INJURY:

1. ISCHEMIC AND HYPOXIC INJURY

2. INJURY DUE TO ACTION OF FREE

RADICALS

3. TOXIC INJURY

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Cause of Hypoxic Injury

1. Ischemia: Lack of blood supply due toobstruction of arterial blood flow.

2. Decreased oxygen carrying capacity of

blood as in anemia and carbon monoxidepoisoning.

3. Decreased oxygenation of blood due torespiratory diseases.

4. Decreased tissue perfusion as inhypotension and shock.

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Generation of Free Radicals

Normal metabolism (oxidation-reductionreactions).

Oxygen toxicity.

Ionizing radiation (X-ray, ultra violet rays). Drug and chemicals.

Cellular aging.

Acute inflammation.

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TOXIC INJURY

Direct action of chemicals (cytotoxic

action)

Action of toxic products of metabolism

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Reversible Injury -- Morphology

Light microscopic changes

Cell swelling

fatty change

Ultrastructural changes

Alterations of cell membrane

Swelling of and small amorphous deposits in

mitochondria Swelling of ER and detachment of ribosomes

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Irreversible Injury -- Morphology

Light microscopic changes

Increased cytoplasmic eosinophilia (loss of RNA,

which is more basophilic)

Cytoplasmic vacuolization Nuclear chromatin clumping

Ultrastructural changes

Breaks in cellular and organellar membranes Larger amorphous densities in mitochondria

Nuclear changes

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Irreversible Injury Nuclear Changes

Pyknosis

Nuclear shrinkage and increased basophilia

Karyorrhexis Fragmentation of the pyknotic nucleus

Karyolysis

Fading of basophilia of chromatin

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Karyolysis & karyorrhexis -- micro

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Alterations may be present by 2

pathological processes:

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Dystrophy (degeneration, accumulation)(from greece dys - disorder & trophe

nourish) is pathological process, in thebase of which the tissue metabolismdisorder lays & it leads to structural

changes of tissues.

Trophics is the whole of mechanismsdefining metabolism and structure of

tissue (cell), which need for realization ofcertain function.

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Mechanisms of trophics:

Cellular

Extracellular

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Mechanism of degenerations:

Disorder of cell autoregulation due tohyperfunction, toxins, radiation,enzyme deficiency etc.

Disorder of transport systems of cell,which leads to hypoxia.

Disorder of endocrine regulation oftrophics (diabetes, hyperthyroidism

etc).

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Degenerationsare accumulation of different products

of metabolism (proteins, lipids,

carbohydrates, minerals, water) in cells

or in intercellular substance, whichcharacterized by quantitative &

qualitative changes because of disorder

of fermentative processes.

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Morphogenetic mechanisms of

degenerations:

Infiltration Decomposition

Unnatural

synthesisTransformation

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Infiltration is excessive accumulation of

metabolism products in cells or in intercellular

substance due to disorder of fermentativesystems (infiltration of intima of arteries by

lipoproteids in atherosclerosis).

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Decomposition is decay ofultrastructures of cells & intercellular

substance, which leads to disorder of

tissue metabolism & accumulation ofproducts of metabolism in tissue (cell)

(dystrophy of cardiomyocytes in

dyphteria).

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Unnatural synthesis is synthesis ofunusual substances, which are not

present in normal cells & tissues)

(synthesis of alcoholic hyaline inhepatocytes).

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Transformation

is formation of products of one kind of

metabolism from common initial

products, which are need for formation

of proteins, lipids & carbohydrates

(transformation of components of fat &

carbohydrate in proteins).

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Classification of degenerations:

depending oflocalization of

pathological changes Intracellular

accumulations

Extracellular

accumulations Miscellaneous

variants

depending of geneticfactors Acquired Inherited

depending of type ofmetabolism disorder

proteinaccumulations

fatty accumulations

carbohydrate

accumulations mineral

accumulations

depending ofprevalence of process

general

local