Classification.

1. According to aethiology (chromosome or genomic mutation characterization).

2. According to cell type in which occured the mutation occure:

• Gametic mutations.

• Somatic mutations (in such occasions organism with cells of different chromosome constitution developes; such chromosome diseases forms are called mozaic ones).

3. According to the generation in which the mutation arises:

• Sporadic – mutations occured de novo ingametes of healthy parents.

• Inherited or family mutation forms – parents already have got such anomaly.

Phenocopy- phenotype non-hereditary changing occurring under external factors influence which looks like mutations by its expression. Example: glucosuria, fructosuria several types.

Hereditary factors importance in human pathology:

1. all organs systems can be injured: 250 diseases in dermatology, more than 200 in ophthalmology, about 200 in neurology;

2. 1,5-2,0% of all hereditary diseases – gene ones;

3. 20-30% of all children suffer from hereditary diseases;

4. 0,7% of all new-borned have hereditary diseases;

5. 40% of abortions and 6% of dead-borned – due to hereditary pathology;

6. many diseases with hereditary predisposition (atherosclerosis, diabetes, hypertonic disease, shizophreny), many multifactorial diseases (genotype+environmental factors).

16. The concept of primary and secondary alteration. Molecular mechanisms of cell injury. Lipid mechanisms role in alteration pathogenesis.

Cell injury – is a typical pathological process, the base of which are intracellular homeostasis disorders leading to cell structural integrity and its functional abilities disorder.

Types:

1. dependently on development velocity and main features expression: acute and chronic injury;

2. dependently on intracellular homeostasis disorder degree: reversible and irreversible;

3. dependently on life cycle period at which injured agent acts to: mitotic and interphase;

4. dependently on pathogenetic mechanisms inducing the injury: violent and cytopathic.

Primary (direct) cells injury reasons:

1. physical (mechanic action, high and low temperature, ionizing irradiation et al.);

2. chemical (acids, alkalis, low-molecular organic chemicals, enzymes and others);

3. biological (viruses, bacteria, protozoa).

Secondary (indirect) cells injury reason –

it occurs as a result of organism environment constancy primary disorders (hypoxy, acidosis, alkalosis, hyper- and hypoosmy, hypoglycaemia).

Signs testifying cellular injury:

1. Structural – are detected with histological and electronic-microscopic investigative methods and are pathological anatomy subject.

2. Functional – are as follows as: electrophysiological processes disturbances (plasmatic membrane depolarization, excitability and conductance features changing, parabiosis development); contractiveness, exo- and endocytosis disorders; cellular division disorders as well as intercellular contacts and interactions; changings in nervous and humoral regulatory influencings perception.

3. Physical-chemical – they include disorders from side of cellular colloids (cytoplasm and nucleus colloids dispersity degree diminishing, cytoplasm viscosity increasing, sorbtional features changings towards to vital stainings) as well as watery-salty metabolism changings (sodium and calcium ions cytoplasmic concentration increasing while potassium ions decreasing, cell and its separate organells oedema, hydrogenic ions accumulation –injury acidosis).

4. Biochemical: a) macroergs (ATP, creatinephosphate) level decreasing and their hydrolytic decomposition products (creatine, ADP, AMP, inorganic phosphate) level decreasing; 2) tissular respiration inhibiting; 3) oxidation and phosphorylation dissociation; 4) glycolysis activation; 5) proteolysis activation; 6) desamination processes intensivity increasing.

5. Thermodynamic – a) decompartmentalization; b) macromolecules conformational changings occurring in the direction of maximally advantageous thermodynamic state (denaturation); c) large molecules decomposition to smaller and less complicated; d) concentrational gradients making equal between cellular compartments as well as between cell and extracellular environment.

Molecular mechanisms:

15. Lipid – peroxidative lipid oxidation, membrane phospholipases activation, free fatty acids detergent action.

16. Calcium.

17. Electrolyte-osmotic.

18. Acidotic.

19. Proteinic.

20. Nucleinic.