Cell injury (alteration). Degeneration. Cellular & extracellular mechanisms of trophics. Causes of development of degenerations. Morphogenetic mechanisms. Classification.

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.

Alteration (from lat. Alteratio change, modification) is a change of structure of cell, intercellular substance, tissues & organs, which is accompanied by disorder of their vital functions.

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

Cell injury

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)

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

Mechanism of Free Radical Injury

Lipid peroxidation damage to cellular and organellar membranes DNA damage due to reactions of free radicals with thymine Protein cross-linking and fragmentation due to oxidative modification of amino acids and proteins

The defensive mechanism of free radicals:

a) Intracellular protective enzymes e.g. glutathione peroxidase, catalase, superoxide dismutase.
b) Antioxidants e.g. Vit. E, C.

Loss of calcium homeostasis

Membrane damage and loss of calcium homeostasis 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

Calcium in cell injury

KINDS OF CELL INJURY:

1. ISCHEMIC AND HYPOXIC INJURY 2. INJURY DUE TO ACTION OF FREE RADICALS 3. TOXIC INJURY

Cause of Hypoxic Injury

1. Ischemia: Lack of blood supply due to obstruction of arterial blood flow. 2. Decreased oxygen carrying capacity of blood as in anemia and carbon monoxide poisoning. 3. Decreased oxygenation of blood due to respiratory diseases. 4. Decreased tissue perfusion as in hypotension and shock.

Generation of Free Radicals

Normal metabolism (oxidation-reduction reactions). Oxygen toxicity. Ionizing radiation (X-ray, ultra violet rays). Drug and chemicals. Cellular aging. Acute inflammation.

TOXIC INJURY
Direct action of chemicals (cytotoxic action) Action of toxic products of metabolism

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

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

Irreversible Injury Nuclear Changes

Pyknosis
Nuclear shrinkage and increased basophilia

Karyorrhexis
Fragmentation of the pyknotic nucleus

Karyolysis
Fading of basophilia of chromatin

Karyolysis & karyorrhexis -- micro

Alterations may be present by 2 pathological processes:

Dystrophy (degeneration, accumulation) (from greece dys - disorder & trophe nourish) is pathological process, in the base of which the tissue metabolism disorder lays & it leads to structural changes of tissues. Trophics is the whole of mechanisms defining metabolism and structure of tissue (cell), which need for realization of certain function.

Mechanisms of trophics:
Cellular Extracellular

Mechanism of degenerations:

Disorder of cell autoregulation due to hyperfunction, toxins, radiation, enzyme deficiency etc. Disorder of transport systems of cell, which leads to hypoxia. Disorder of endocrine regulation of trophics (diabetes, hyperthyroidism etc).

Degenerations
are accumulation of different products of metabolism (proteins, lipids, carbohydrates, minerals, water) in cells or in intercellular substance, which characterized by quantitative & qualitative changes because of disorder of fermentative processes.

Morphogenetic mechanisms of degenerations:

Infiltration Decomposition

Unnatural synthesis

Transformation

Infiltration is excessive accumulation of metabolism products in cells or in intercellular substance due to disorder of fermentative systems (infiltration of intima of arteries by lipoproteids in atherosclerosis).

Decomposition is decay of ultrastructures of cells & intercellular substance, which leads to disorder of tissue metabolism & accumulation of products of metabolism in tissue (cell) (dystrophy of cardiomyocytes in dyphteria).

Unnatural synthesis is synthesis of unusual substances, which are not present in normal cells & tissues) (synthesis of alcoholic hyaline in hepatocytes).

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).

Classification of degenerations:
Intracellular accumulations Extracellular accumulations Miscellaneous variants
depending of depending of type of localization of metabolism disorder pathological changes protein

accumulations fatty accumulations carbohydrate accumulations mineral accumulations

depending of genetic factors

Acquired Inherited

depending of prevalence of process general local