Medical brain notes 15

  CAUSES OF CELLULAR INJURY Hypoxia  is the most common cause of injury; it occurs when lack of oxygen preventsthe cell from synthesizing sufficient ATP by aerobic oxidation. Major mechanisms leading to hypoxia are ischemia, cardiopulmonary failure, and decreased oxygen-carrying capacity of the blood (e.g., anemia).  Ischemia , due to a loss of blood supply, is the most common cause of hypoxia, and is typically related to decreased arterial flow or decreased venous outflow (e.g., atherosclerosis, thrombus, thromboembolus). Pathogens  (viruses, bacteria, parasites, fungi, and prions) can injure the body bydirect infection of cells, production of toxins, or host inflammatory response. Immunologic dysfunction  includes hypersensitivity reactions and autoimmune diseases. Congenital disorders  are inherited genetic mutations (e.g., inborn errors of metabolism). Chemical injury  can occur with drugs, poisons (cyanide, arsenic, mercury, etc.), pol-lution, occ...

  CELLULAR CHANGES DURING INJURY Cellular responses to injury  include adaptation (hypertrophy or atrophy, hyperplasiaor metaplasia), reversible injury, and irreversible injury and cell death (necrosis, apoptosis, or necroptosis). The  cellular response to injury depends on several important factors , including the type of injury, duration (including pattern) of injury, severity and intensity of injury, type of cell injured, the cell’s metabolic state, and the cell’s ability to adapt. The  critical intracellular targets that are susceptible to injury  are DNA, produc-tion of ATP via aerobic respiration, cell membranes, and protein synthesis. Important mechanisms of cell injury  are as follows: ·              Damage to DNA, proteins, lipid membranes, and circulating lipids (LDL) can be caused by oxygen-derived free radicals, including superoxide anion (O 2 • – ), hydroxyl radical (OH • ), and hydrog...

  CELL DEATH Morphologic types of necrosis  (cell death in living tissue, often with an inflamma-tory response) are as follows: ·              Coagulative necrosis , the most common form of necrosis, is most often due toischemic injury (infarct). It is caused by the denaturing of proteins within the cytoplasm. Microscopic examination shows loss of the nucleus but preservation of cellular shape. Coagulative necrosis is common in most organs, including the heart, liver, and kidney, but not the brain. ·              Liquefaction necrosis  results from cellular destruction by hydrolytic enzymes,leading to autolysis (release of proteolytic enzymes from injured cells) and het-erolysis (release of proteolytic enzymes from inflammatory cells). Liquefaction necrosis occurs in abscesses, brain infarcts, and pancreatic necrosis. ·      ...

  CELLULAR ADAPTIVE RESPONSES TO INJURY In general, cellular adaptation is a potentially reversible change in response to the environment. Atrophy  is a decrease in cell/organ size and functional ability. Causes of atrophyinclude decreased workload/disuse (immobilization); ischemia (atherosclerosis); lack of hormonal or neural stimulation, malnutrition, and aging. Light microscopic examination shows small shrunken cells with lipofuscin granules. Electron microscopy shows decreased intracellular components and autophagosomes. Hypertrophy  is an increase in cell size and functional ability due to increased syn-thesis of intracellular components. Causes of hypertrophy include: ·              Increased mechanical demand can be physiologic (striated muscle of weight lifters) or pathologic (cardiac muscle in hypertension).   ·              Increased endoc...

  OTHER CELLULAR ALTERATIONS DURING INJURY Pathologic Accumulations ·              Lipids  that can accumulate intracellularly include triglycerides (e.g., fattychange in liver cells), cholesterol (e.g., atherosclerosis, xanthomas), and com-plex lipids (e.g., sphingolipid accumulation). ·              Proteins  can accumulate in proximal renal tubules in proteinuria and canform Russell bodies (intracytoplasmic accumulation of immunoglobulins) in plasma cells. ·              Glycogen storage diseases ·                Exogenous pigments  include anthracotic pigmentation of the lung (secondaryto the inhalation of carbon dust), tattoos, and lead that has been ingested (e.g., gingival lead line, renal tubular lead deposits). E...