Ischemic Cell Injury
Ischemia is a reduction or complete cessation of blood flow in organs. This process consistently develops in ischemic heart disease (IHD), cerebrovascular diseases, systemic atherosclerosis, hypertension, and vasculitis.
The morphological outcome depends on the severity and duration of oxygen deprivation:
- Mild or chronic course leads to tissue atrophy or the triggering of programmed cell death — apoptosis.
- Acute severe ischemia causes necrosis. Clinically, this manifests as infarction (coagulative or liquefactive) or gangrene (dry or wet).
Pathogenesis (Morphogenesis): Destruction of ultrastructures begins with a state of anoxia, which triggers a lethal cascade:
- Mitochondrial damage $\rightarrow$ energy depletion.
- Activation of anaerobic glycolysis.
- Impairment of membrane ion pumps.
- Intracellular accumulation of $Ca^{2+}$ ions.
- Activation of $Ca^{2+}$-dependent phospholipases and proteases.
- Irreversible destruction of cell membranes.
Free Radical-Mediated Cell Death
Free radicals are unstable and highly reactive ions or molecules with an unpaired electron in their outer electron shell. Once formed, they act as catalysts for chain reactions, generating new radicals.
Normally, they are produced in small quantities as a byproduct of cellular respiration and are immediately neutralized by natural antioxidants. Leukocytes purposefully utilize these reactive molecules to destroy bacteria. Pathology begins when protective mechanisms fail and radicals accumulate to toxic concentrations.
Main Oxygen Derivatives and Enzymatic Defense:
- Superoxide anion radical ($O_2^{-\bullet}$) $\rightarrow$ inactivated by the enzyme superoxide dismutase.
- Hydrogen peroxide ($H_2O_2$) $\rightarrow$ neutralized by catalase and glutathione peroxidase.
- Hydroxyl radical ($OH^{\bullet}$).
Mechanisms of Cell Damage:
- Lipid peroxidation (LPO): leads to fatal damage of cell membranes.
- Protein cross-linking: results in the inactivation of vital enzymes.
- DNA strand breaks: leads to impaired transcription and mutagenesis.
Cell Death Caused by Ionizing Radiation
Radiation injury is divided into two types. Direct injury causes immediate destruction of DNA and cellular structures. Indirect injury is associated with the production of active oxygen radicals. This produces the "bystander effect," where radicals damage not only the irradiated cell itself but also neighboring intact tissues.
High-energy irradiation is lethal and causes necrosis or apoptosis. Low-energy injury provokes mutations, increasing the risk of malignant transformation (carcinogenesis).
Internal irradiation is the most hazardous. Radionuclides can enter through the respiratory tract, gastrointestinal tract, wounds, and even intact skin.
Pathogenesis Using the Lungs as an Example: Radionuclides entering the tissue cause DNA breaks and the release of free radicals, initiating an inflammatory response. Neutrophils, macrophages, and lymphocytes rush into the interstitium and alveoli, becoming an additional source of tissue damage. Blood vessels are injured, plasma leaks into extravascular zones (transudate), initiating fibrosis.
Small particles damage the mucosa of bronchi, bronchioles, and alveoli, causing bronchitis, bronchiolitis, and idiopathic pulmonary fibrosis (IPF). A vicious cycle forms: developing pneumosclerosis disrupts lymph and blood circulation, which prevents the clearance of radioactive material and promotes its further accumulation.