Primary alterations of the genetic apparatus
The impact of pathogenic factors on the genetic apparatus leads to fatal consequences for the cell. There are four main scenarios of primary damage:
- Mutations. Persistent, irreversible changes in the genotype are formed.
- Activation of pathogenic genes. "Sleeping" or abnormal DNA segments are triggered, whose expression is normally suppressed.
- Blockade of normal expression. The synthesis of physiologically essential proteins is distorted or completely halted.
- Integration of foreign DNA. Exogenous fragments are inserted into the genome (a typical example is viral infection).
Cascade of disruptions in template processes
Primary defects inevitably entail failures in fundamental vital processes. The cell loses the ability to correctly process information at all stages:
- Replication (DNA duplication prior to division) is disrupted.
- Transcription (RNA synthesis on a DNA template) suffers.
- Translation (direct assembly of the protein molecule) is distorted.
- Repair is suppressed (the capacity to restore damaged regions decreases).
The outcome is a disorder of the cell cycle: the cell loses the ability to undergo adequate division and proliferation, which is a direct path to malignancy.
Disorganization of regulatory systems
In addition to direct DNA damage, vital activity is disrupted due to the breakdown of control systems at the receptor and post-receptor levels. The cell ceases to respond adequately to biologically active substances (BAS). This occurs via three pathways:
- Change in receptor number. The density of receptors on the membrane or within the cytoplasm may pathologically increase or decrease.
- Impaired sensitivity. The affinity of the receptor for its ligand is decreased or distorted.
- Breakdown of intracellular messengers. Secondary messengers and phosphorylation cascades fail to transmit the signal from the receptor to effector structures.
Standard forms of cell pathology
Genetic and regulatory failures lead to the development of standard pathological processes. These include:
- Dysplasia (disruption of differentiation, growth, and development).
- Dystrophy (metabolic failure with structural changes).
- Necrosis (cell death).
- Pathological variants of apoptosis.
- Defects of individual subcellular structures.
Cellular dystrophies: mechanisms of development
Dystrophy occurs when plastic processes and metabolism are disrupted. Four mechanisms of its development are distinguished:
- Synthesis of abnormal substances (for example, the formation of the protein-polysaccharide amyloid complex).
- Excessive transformation (the transformation of certain compounds into others beyond normal levels, e.g., carbohydrates into fats).
- Decomposition (phanerosis) (breakdown of membrane protein-lipid complexes and other subcellular structures).
- Infiltration (penetration of an excess of substances into the cell, e.g., calcium ions or low-density lipoproteins in atherogenesis).
Depending on which type of metabolism is affected, dystrophies are divided into protein (dysproteinoses), lipid (lipidoses), carbohydrate, pigmentary (dyspigmentoses), mineral, and storage diseases (thesaurosis).
Features of protein and lipid dystrophies
Protein dystrophies are accompanied by changes in the physicochemical properties of proteins, leading to the loss of their structural and enzymatic functions. This process often goes through three consecutive stages leading to necrosis: granular, hyaline-droplet, and hydropic.
Lipid dystrophies manifest as the accumulation of lipids where they should not be, an increase in their quantity, or a change in their chemical composition. They are classified as primary (genetic enzymopathies, such as sphingomyelin lipidosis) and secondary (the result of exogenous or endogenous factors: ethanol, barbiturates, cytostatics, phosphorus compounds).
Briefly: answers to topical questions
Which secondary messengers and cascades are damaged when intracellular messengers break down?
When the function of intracellular messengers is impaired, a failure occurs in the signal transduction system from receptors to effector structures, damaging secondary messengers and phosphorylation cascades.
The following messengers and systems are damaged:
- Secondary messengers — Ca²⁺ ions, cAMP, cGMP, diacylglycerol (DAG), and inositol-1,4,5-trisphosphate (IP3).
- Phosphorylation cascades — the adenylate cyclase cascade (involving G proteins and protein kinase A), as well as cascades involving protein kinase C.
Disruption of their production or metabolism can be caused by bacterial toxins. For example, cholera enterotoxin persistently activates adenylate cyclase with the accumulation of cAMP, while the heat-stable enterotoxin of E. coli increases cGMP levels. Lithium salts disrupt the production of DAG, IP3, and cAMP, while non-hydrolyzable DAG analogs (phorbol esters) promote tumor development.
Which hereditary enzymopathies lead to the development of primary lipid dystrophies?
The development of primary lipid dystrophies (systemic lipidoses) is caused by hereditary or congenital enzymopathies characterized by a deficiency of lipid metabolism enzymes.
Such conditions (storage diseases or thesaurismoses) include:
- Cerebroside lipidosis — Gaucher disease (destruction of glycolipids).
- Sphingomyelin lipidosis — Niemann-Pick disease.
- Ganglioside lipidosis — Tay-Sachs disease.
- Generalized ganglioside lipidosis — Norman-Landing disease.
- Glycosphingolipidosis — Fabry syndrome.
Deficiency of the corresponding enzyme leads to the intracellular accumulation of non-metabolized substrate (lipids) with predominant damage to the liver, spleen, bone marrow, and central nervous system.
To remember the four mechanisms of dystrophy, use the acronym "SIDI": Synthesis (abnormal), Infiltration, Decomposition, Excessive transformation.
Class and exam questions
What is the main danger of cell genome damage?
The main threat lies in the risk of oncogenesis and malignant transformation due to irreversible failures in the cell cycle.
What is decomposition or phaneroisis?
This is one of the mechanisms of dystrophy development characterized by the pathological breakdown of subcellular structures and substances, such as protein-lipid complexes of cell membranes.
How do pathogenic factors affect cell receptors?
They can alter receptor density on the membrane as well as impair their affinity for biologically active substances, blocking signal transduction.
What else to study on this topic
- Stages of development of protein dystrophies: from granular to hydropic
- Primary lipidoses: ganglioside, cerebroside, and sphingomyelin lipidosis
- The effect of drugs (cytostatics, antibiotics) on the development of secondary lipidoses
- Pathological forms of apoptosis and necrosis as outcomes of cell injury
- Structural and functional disorders of mitochondria and lysosomes
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