Lecture 2 Cellular injury.pdf

CELLULAR INJURY PROF. DR. DALYA BASIL  CELLULAR INJURY ◼ Cellular injury can occur in a number of different ways. The extent of injury that cells experience is often related to the intensity and duration of exposure to the injurious event or substance. Cellular injury may be a...

CELLULAR INJURY PROF. DR. DALYA BASIL  CELLULAR INJURY ◼ Cellular injury can occur in a number of different ways. The extent of injury that cells experience is often related to the intensity and duration of exposure to the injurious event or substance. Cellular injury may be a reversible process, in which case the cells can recover their normal function, or it may be irreversible and lead to cell death.  CELLULAR INJURY ◼ Causes of Cell Injury Cell damage can occur in many ways (the ways by which cells are injured have been grouped into five categories): (1) injury from physical agents (2) radiation injury (3) chemical injury (4) injury from biologic agents (5) injury from nutritional imbalances.  CELLULAR INJURY ◼ Injury from Physical Agents: ◼ Physical agents responsible for cell and tissue injury include mechanical forces (occurs as the result of body impact with another object, these types of injuries split and tear tissue, fracture bones, injure blood vessels, and disrupt blood flow), extremes of temperature, (Extremes of heat and cold cause damage to the cell, its organelles, and its enzyme systems). Exposure to low-intensity heat 43ºC to 46ºC, such as occurs with partial-thickness burns and severe heat stroke, causes cell injury by inducing vascular injury, and disrupting the cell membrane. With more intense heat, coagulation of blood vessels and tissue proteins occurs. ◼ Exposure to cold increases blood viscosity and induces vasoconstriction by direct action on blood vessels and through reflex activity of the sympathetic nervous system, and this will lead to hypoxic tissue injury, depending on the degree and duration of cold exposure. CELLULAR INJURY ◼ Injuries due to electrical forces: ◼ Can affect the body through extensive tissue injury and disruption of neural and cardiac impulses. The effect of electricity on the body is mainly determined by its voltage, the type of current (i.e., direct or alternating), its amperage, the resistance of the intervening tissue, the pathway of the current, and the duration of exposure. Electrical burn of the skin. The victim was electrocuted after attempting to stop a fall from a ladder by grasping a high-voltage line.  CELLULAR INJURY ◼ Radiation Injury: ◼ Ionizing Radiation: Ionizing radiation affects cells by causing ionization of molecules and atoms in the cell, by directly hitting the target molecules in the cell, or by producing free radicals that interact with critical cell components. It can immediately kill cells, interrupt cell replication, or cause a variety of genetic mutations, which may or may not be lethal. Most radiation injury is caused by localized irradiation that is used in the treatment of cancer.  CELLULAR INJURY ◼ The injurious effects of ionizing radiation vary with the dose, dose rate, and the differential sensitivity of the exposed tissue to radiation injury. Because of the effect on deoxyribonucleic acid (DNA) synthesis and interference with mitosis, rapidly dividing cells of the bone marrow and intestine are much more vulnerable to radiation injury than tissues such as bone and skeletal muscle. ◼ Many of the clinical manifestations of radiation injury result from acute cell injury, dose-dependent changes in the blood vessels that supply the irradiated tissues, and fibrotic tissue replacement.  CELLULAR INJURY ◼ Ultraviolet Radiation: UV radiation contains increasingly energetic rays that are powerful enough to disrupt intracellular bonds and cause sunburn and increase the risk of skin cancers. Skin damage induced by UV radiation is thought to be caused by reactive oxygen species and by damage to melanin-producing processes in the skin. ◼ Nonionizing Radiation: Nonionizing radiation includes infrared light, ultrasound, microwaves, and laser energy. Nonionizing radiation exerts its effects by causing vibration and rotation of atoms and molecules.  CELLULAR INJURY ◼ Chemical Injury: ◼ Chemical agents can injure the cell membrane and other cell structures, block enzymatic pathways, coagulate cell proteins, and disrupt the osmotic and ionic balance of the cell. Corrosive substances such as strong acids and bases destroy cells as the substances come into contact with the body. Other chemicals may injure cells in the process of metabolism or elimination. Carbon tetrachloride (CCl4), for example, causes little damage until it is metabolized by liver enzymes to a highly reactive free radical carbon tetrachloride (CCl3). Carbon tetrachloride is extremely toxic to liver cells.  CELLULAR INJURY ◼ Drugs. Many drugs—alcohol, prescription drugs, over-the-counter drugs, and street drugs—are capable of directly or indirectly damaging tissues. Ethyl alcohol can harm the gastric mucosa, liver, developing fetus, and other organs. Antineoplastic (anticancer) and immunosuppressant drugs can directly injure cells. ◼ Other drugs produce metabolic end products that are toxic to cells. Acetaminophen, a commonly used over-the-counter analgesic drug, is detoxified in the liver, where small amounts of the drug are converted to a highly toxic metabolite. This metabolite is detoxified by a metabolic pathway that uses a substance (i.e., glutathione) normally present in the liver. When large amounts of the drug are ingested, this pathway becomes overwhelmed and toxic metabolites accumulate, causing massive liver necrosis.  CELLULAR INJURY ◼ Injury from Biologic Agents: ◼ Biologic agents are able to replicate and can continue to produce their injurious effects, biologic agents injure cells by diverse mechanisms. Viruses enter the cell and become incorporated into its DNA synthetic machinery. Certain bacteria elaborate exotoxins that interfere with cellular production of ATP. Other bacteria, such as the gram-negative bacilli, release endotoxins that cause cell injury and increased capillary permeability.  CELLULAR INJURY ◼ Injury from Nutritional Imbalances: ◼ Nutritional excesses and nutritional deficiencies predispose cells to injury. Obesity and diets high in saturated fats are thought to predispose persons to atherosclerosis. The body requires more than 60 organic and inorganic substances in amounts ranging from micrograms to grams. These nutrients include minerals, vitamins, certain fatty acids, and specific amino acids. Dietary deficiencies can occur in the form of starvation, in which there is a deficiency of all nutrients and vitamins, or because of a selective deficiency of a single nutrient or vitamin. Iron-deficiency anemia, scurvy, beriberi, and pellagra are examples of injury caused by a lack of specific vitamins or minerals. The protein and calorie deficiencies that occur with starvation cause widespread tissue damage.