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7/27/2019 Lec # 2 Pat Anat
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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