Cell Injury and Biochemistry Quiz

Cell Injury and Death

• Cell injury is the initial response of a cell to damaging stimuli.
• The response depends on the type, duration, and severity of the injury.
• Consequences depend on the type of injury, cell status, adaptability, and genetic makeup.
• Cell injury can be reversible or irreversible.
• Reversible injury can potentially return to normal cell function.
• Irreversible injury leads to cell death.
• Cell death can occur through necrosis or apoptosis.

Causes of Cell Injury

• Oxygen deprivation (hypoxia/ischemia)
• Nutrient deficiencies (protein, vitamins, iron, copper)
• Chemical agents
• Infectious agents
• Physical agents
• Immunological reactions (allergies, anaphylaxis, autoimmunity, immunodeficiency)
• Genetic defects (e.g., Down syndrome, sickle cell anemia)

Factors Affecting Cell Injury

• Cellular response to injurious stimuli depends on its type, duration, and severity.
• Consequences of an injurious stimulus depend on the type of injury, the cell's status, its adaptability, and its genetic makeup.

Changes Following Physiological or Pathological Stimuli

• Cell injury (reversible or irreversible)
• Necrosis and apoptosis
• Adaptive changes

General Biochemical Mechanisms

• ATP depletion (oxygen deprivation, hypoxia, ischemia, glucose unavailability, impaired transport)
• Protein synthesis disruption.
• Metabolic pathway disturbances.
• Reactive oxygen species generation (radiation, toxins, chemicals, lipid peroxidation)

Loss of Calcium Homeostasis

• Ischemia or toxins activate phospholipases, proteases, endonucleases, and ATPases.
• Increased cytosolic calcium disrupts cellular function leading to damage.

Mitochondrial Dysfunction

• Mitochondrial dysfunction induced by various stimuli results in a mitochondrial permeability transition (MPT)
• MPT results in proton gradient decay, cytochrome C release, and apoptotic consequences.

Free Radical-Induced Injury

• Free radicals are generated through reduction-oxidation reactions, nitric oxide, absorption of radiant energy (ionizing radiation), and enzymatic metabolism of exogenous chemicals (e.g., CCl4).
• Effects include lipid peroxidation, DNA damage, and protein cross-linking.
• Antioxidant defenses (e.g., vitamin E, glutathione peroxidase) and enzymes play a crucial role in counteracting free radical damage.

Superoxide Dismutase, Glutathione Peroxidase, and Catalase

• Superoxide dismutase converts superoxide radicals to hydrogen peroxide.
• Glutathione peroxidase converts hydrogen peroxide to water.
• Catalase also converts hydrogen peroxide to water.

Chemical Injury

• Some chemicals directly react with critical cellular components or organelles (antibiotics, antineoplastic agents) affecting ion transport and increasing membrane permeability.
• Other chemicals (e.g., CCl4) need metabolic activation to become toxic free radicals.
• These toxins damage membranes by reacting directly with lipids and proteins.

Cellular Swelling

• Cellular swelling (cloudy swelling) is an early reversible response to various injuries.
• The cause is often a shift of extracellular fluid into the cell due to impaired cellular metabolism.
• It is characterized by increased cell size and granular cytoplasm.

Mechanisms of Free Radical Injury

• Lipid peroxidation of membranes by free radicals.
• Damage to proteins due to free radical cross-linking of protein sulfhydryl bonds.
• Damage to DNA due to free radical reaction with DNA components.

Inactivation of Free Radicals

• Involves Endogenous or exogenous antioxidants and enzymes.

Free Radical Cell Injury

• Free radical injury is a final common pathway in various cellular injuries, including chemical and radiation damage, phagocytosis, aging, and cancer.

Elements

• All matter in the universe is composed of basic units known as elements.
• Elements are fundamental substances made of only one type of atoms (e.g., hydrogen, nitrogen, oxygen).
• Carbon, hydrogen, nitrogen, and oxygen are the major elements that make up about 96% of the body.

Atom

• Atoms are composed of protons, neutrons, and electrons.
• The nucleus contains protons and neutrons.

Free Radicals

• Free radicals are atoms or groups of atoms bearing one or more unpaired electrons.
• They are extremely reactive and cause various cellular damages.
• Four major free radicals exist: superoxide, hydrogen peroxide, hydroxyl radicals, singlet oxygen.