Various Causes And Morphological Changes In Cell Injury

Various Causes And Morphological Changes In Cell Injury

Define Cell Injury. Describe Various Causes And Morphological Changes In Cell Injury.
Answer:

If the limits of adaptive response to a stimulus are exceeded, or in certain instances when adaptation is not possible, a sequence of events follows, loosely termed cell injury.

• Cell injury is reversible up to a certain point, but if the stimulus persists or is severe enough from the beginning, the cell reaches the “point of no return” and suffers irreversible cell injury and cell death.

Causes Of Cell Injury

Causes of cell injury are divided into two parts, i.e., genetic and acquired.

Genetic Cause

The genetic injury may result in a defect as gross as the congenital malformations associated with Down syndrome or as subtle as the single amino acid substitution in hemoglobin S in sickle cell anemia.

The many inborn errors of metabolism arising from enzymatic abnormalities, usually an enzyme lack, are excellent examples of cell damage due to subtle alterations at the level of DNA.

Causes of cell injury

Acquired Causes

• Hypoxia and ischemia: Cells of different tissues essentially require oxygen to generate energy and perform metabolic functions. Deficiency of oxygen or hypoxia results in the failure to carry out these activities by the cells.
  Hypoxia is the most common cause of cell Injury. The most common mechanism of hypoxic cell injury is a reduced supply of blood to cells, i.e., Ischemia. However, oxygen deprivation of tissues may result from other causes as well, For example, carbon monoxide poisoning, cardiorespiratory insufficiency, and increased demand for tissues.
• Physical agents: Physical agents include mechanical trauma, extremes of temperature (burns and deep cold), sudden changes in atmospheric pressure, radiation, and electric shock.
• Chemicals and drugs: Simple chemicals such as glucose or salt in hypertonic concentrations may cause cell injury directly or by deranging electrolyte homeostasis of cells. Even oxygen, in high concentrations, is severely toxic. Trace amounts of agents known as poisons, such as arsenic, cyanide, or mercuric salts, may destroy sufficient numbers of cells within minutes to hours to cause death. Other substances, however, are our daily companions— environmental and air pollutants, insecticides, and herbicides; industrial and occupational hazards, such as carbon monoxide and asbestos; social stimuli, such as alcohol and narcotic drugs; and the ever-increasing variety of therapeutic drugs.
• Microbial agents: Injuries by microbes include infections caused by bacteria, rickettsiae, viruses, fungi, protozoa, metazoa, and other parasites.
• Immunologic agents: Immunity is a ’double-edged sword’, it protects the host against various injurious agents, but it may also turn lethal and cause cell injury, For Example. Hypersensitivity reactions, anaphylactic reactions, and autoimmune diseases.
• Nutritional derangements: A deficiency or an excess of nutrients may result in nutritional imbalances. Nutritional deficiency diseases may be due to overall deficiency of nutrients (For Example. starvation), protein calories (For Example. marasmus, kwashiorkor), minerals (For Example. anemia), or trace elements. Nutritional excess is a problem in affluent societies, resulting in obesity, atherosclerosis, heart disease, and hypertension.
• Psychologic factors: There are no specific biochemical or morphologic changes in common acquired mental diseases due to mental stress, strain, anxiety, overwork, and frustration, For Example.Depression, schizophrenia. However, problems of drug addiction, alcoholism, and smoking result in various organic diseases such as liver damage, chronic bronchitis, lung cancer, peptic ulcer, hypertension, ischemic heart disease, etc.

Morphological changes in cell injury

Morphological Changes In Cell Injury

Following are the morphological changes in cell injury:

Reversible Cell Injury

• Cellular swelling is the first manifestation of almost all forms of injury to cells. On microscopic examination, small clear vacuoles may be seen within the cytoplasm; these represent distended and pinched-of segments of the endoplasmic reticulum.
• This pattern of nonlethal injury is sometimes called hydropic change or vacuolar degeneration. The swelling of cells is reversible. The ultrastructural changes of reversible cell injury include:
  • Plasma membrane alterations, such as blebbing, blunting, and distortion of microvilli; creation of myelin figures; and loosening of intercellular attachments
  • Mitochondrial changes, including swelling, rarefaction, and the appearance of small phospholipid-rich amorphous densities
  • Dilation of the endoplasmic reticulum with detachment and disaggregation of polysomes
  • Nuclear alterations, with disaggregation of granular and fibrillar elements.

Irreversible cell injury histology

Irreversible Cell Injury

Cell Death or Necrosis

• Necrotic cells show increased eosinophilia.
• The cell may have a more glassy homogeneous appearance than that of normal cells, mainly as a result of the loss of glycogen particles.
• When enzymes have digested the cytoplasmic organelles, the cytoplasm becomes vacuolated and appears moth-eaten.
• Finally, calcification of the dead cells may occur.
• Nuclear changes appear in the form of one of three patterns, all due to nonspecific breakdown of DNA. The basophilia of the chromatin may fade (karyolysis), a change that presumably reflects DNase activity. A second pattern is pyknosis, characterized by nuclear shrinkage and increased basophilia. Here, the DNA condenses into a solid, shrunkenbasophilic mas, in the third pattern, known as karyorrhexis, the pyknotic or partially pyknotic nucleus undergoes fragmentation. With time (a day or two), the nucleus in the necrotic cell disappears.

Programmed Cell Death

The following morphologic features, some best seen with the electron microscope, characterize cells undergoing apoptosis:

• Cell shrinkage: The cell is smaller in size; the cytoplasm is dense, and the organelles, although relatively normal, are more tightly packed.
• Chromatin condensation: This is the most characteristic feature of apoptosis. The chromatin aggregates peripherally, under the nuclear membrane, into well-delimited dense masses of various shapes and sizes. The nucleus itself may break up, producing two or more fragments.
• Formation of cytoplasmic blebs and apoptotic bodies: The apoptotic cell first shows extensive surface blebbing, then undergoes fragmentation into many membrane-bound apoptotic bodies composed of cytoplasm and tightly packed organelles, with or without a nuclear fragment.
• Phagocytosis of apoptotic cells or bodies by adjacent healthy cells, either parenchymal cells or macrophages. The apoptotic bodies are rapidly degraded within lysosomes, and the adjacent cells migrate or proliferate to replace the space occupied by the now-deleted apoptotic cell.

Subcellular Alterations In Cell Injury

Various morphologically distinct alterations at sub-cellular levels are seen in acute and chronic forms of cell injury. They are seen at the level of the cytoskeleton, lysosomes, endoplasmic reticulum, and mitochondria.

Cytoskeletal Changes

• Thin filaments: Thin filaments are composed of actin, myosin, and their associated regulatory proteins. Functioning thin filaments are essential for various stages of leukocyte movement or the ability of such cells to perform phagocytosis adequately. Some drugs and toxins target actin filaments and thus affect these processes. For example, cytochalasin B prevents the polymerization of actin filaments, and phalloidin, a toxin of the mushroom Amanita phalloides, binds actin filaments.
• Microtubules: Defects in the organization of microtubules can inhibit sperm motility, causing male sterility, and at the same time can immobilize the cilia of respiratory epithelium, causing interference with the ability of
  this epithelium to clear inhaled bacteria, leading to bronchiectasis.
• Intermediate filaments: These components provide a flexible intracellular scaffold that organizes the cytoplasm and resists forces applied to the cell. Various classes of intermediate filaments may deposit in the cytosol.

Lysosomal Changes

• Lysosomeshavepowerfulhydrolyticenzymes. Heterophagy and autophagy are two ways by which lysosomes show morphologic changes in phagocytic function.
• Heterophagy: Phagocytosis, i.e., cell eating, and pinocytosis, i.e., Cell drinking, are two forms of heterophagy by which material from outside is taken up by lysosomes of polymorphs and macrophages to form phagolysosomes.
• Autophagy: It is the process by which worn-out intracellular organelles and other cytoplasmic material form an autophagic vacuole that fuses with the lysosome to form autophagy.

Smooth Endoplasmic Reticulum Changes

Hypertrophy of the smooth endoplasmic reticulum occurs, for example, hypertrophy of the smooth endoplasmic reticulum of liver cells occurs as an adaptive change in response to prolonged use of barbiturates.

Mitochondrial Changes

Morphological changes seen in mitochondria are:

• Megamitochondria: It is large mitochondria seen in alcoholic liver disease
• Alteration in the number of mitochondria: Number increases in hypertrophy and decreases in atrophy
• Myopathies are the defects in which mitochondria have abnormal cristae.