cell injury

causes of cell injury

1- oxygen deprivation. hypoxia, or oxygen deficiency, in¬terferes with aerobic oxidative respiration and is an ex¬tremely important and common cause of cell injury and death. ischemia is the most common cause of hypoxia, oxygen deficiency can also result from inadequate oxygenation of the blood, as in pneumonia, or reduction in the oxygen-carrying capacity of the blood. as in anemia or carbon monoxide (co) poisoning.
2- chemical gents. virtually any chemical substance can cause injury even innocuous substances such as glu¬cose or salt. if sufficiently concentrated, may so derange the osmotic environment that injury or cell death results. oxygen at sufficiently high partial pressures is also toxic. agents commonly known as poisons cause severe damage at the cellular level by altering membrane permeability, osmotic homeostasis. or the integrity of an enzyme or co¬factor and can culminate in the death of the whole organ¬ism. other potentially toxic agents are encountered daily in our environment these include air pollutants, insecti¬cides, carbon monoxide, asbestos, and social "stimuli" such as ethanol. even therapeutic drugs can cause cell or tissue injury in a susceptible patient or in the appropriate setting.
3- infectious agents. these range from submicroscopic viruses to meter-long tapeworms in between are the rick¬ettsiae, bacteria, fungi, and protozoa. the diverse ways by which biologic agent] cause injury
4- immunologic reactions. although the immune system defends the body against foreign materials, immune reac¬tions intended or incidental can nevertheless result in cell and tissue injury. anaphylaxis to a foreign protein or a drug is a classic example. moreover,

a loss of tolerance with re¬sponses to self-antigens is the underlying cause of a num¬ber of autoimmune diseases.
5- genetic defects. genetic defects may result in pathologic changes as conspicuous as the congenital malformations asso¬ciated with down syndrome or as subtle as the single amino acid substitution in the hemoglobin s of sickle cell anemia. the several inborn errors of metabolism due to congenital enzymatic deficiencies .
6-nutritional imbalance: nutritional deficiencies remain a major cause of cell injury.ex:protein-calorie insufficiency among underprivileged populations, specific vitamin deficiencies, excesses of nu¬trition are also important causes of morbidity and mortality for example. obesity markedly increases the risk for type 2 formerly called adult-onset, non-insulin-dependent) diabetes mellitus. moreover. diets rich in animal fat are strongly implicated in the development of atherosclerosis as well as in increased vulnerability to many disorders, includ¬ing cancer.
7- physical agents. trauma. extremes of temperatures, radiation, electric shock, and sudden changes in atmos¬pheric pressure all have wide-ranging effects on cells.
8- aging.
general biochemical mechanisms
1-atp depletion. the high-energy phosphates of atp are critical for virtually every process in the cell including the maintenance of cellular osmolarity, transport processes, protein synthesis, and basic metabolic path¬ways. a loss of atp synthesis (via either mitochondria) oxidative phosphorylation or anaerobic glycolysis) re¬sults in rapid shutdown of most critical homeostatic pathways
2-oxygen deprivation or generation of reactive oxygen species. a lack of oxygen obviously underlies the patho¬genesis of cell injury in ischemia, but partially reduced activated oxygen species are also important mediators of cell death. these free radical species cause lipid peroxidation and other deletingrious effects on cell structure.
3- loss of calcium homeostasis. cytosolic free calcium is normally maintained by atp-dependent calcium trans¬porters at concentrations lower than the concentration of extracellular calcium or of sequestered intracellular mitochondria) and endoplas¬mic reticulum calcium. ischemia or toxins allow a net influx of extracellular calcium across the plasma mem¬brane, followed by the release of calcium from the intra¬cellular stores. increased cytosolic calcium in turn activates a variety of phospholipases (promoting mem¬brane damage), proteases (catabolizing structural and membrane proteins), atpases (accelerating atp deple¬tion), and endonucleases (fragmenting genetic material). although cell injury results in increased in¬tracellular calcium, a loss of cal¬cium homeostasis is not always a necessary proximate event in irreversible cell injury.
4- defects in plasma membrane permeability. the plasma membrane may be directly damaged by certain bacterial toxins, viral proteins,…. etc. or secondary to a loss of atp synthesis & calcium-mediated phospholipase activa¬tion. a loss of membrane barriers leads to a breakdown of the concentration gradients of metabolites necessary to maintain normal metabolic activities.



5-mitochondrial damage. mitochondrial damage is caused either directly or indirectly due to increases in cytoslic calcium, intracellular oxidative stress, and lipid breakdown products. all these factors lead to formation oe non selective nonselective pores which allow the proton gradient across the mitochondria membrane to dissipate, thereby preventing atp generation. cytochrome c (an important soluble protein in the electron transport chain) also leaks out into the cytoplasm where it activates apoptosis.

examples of cell injury

ischemia, hypoxia injury
ischemia is most common type of cell in¬jury in clinical medicine. typically occurring because of di¬minished blood flow in a particular tissue s vascular bed. in ischemia aerobic energy generation will cease and anaerobic energy generation also ceases in ischemic tissues after potential substrates are exhausted or when glycolysis is inhibited by the accumula¬tion of metabolites that would normally be removed by blood flow. consequently. ischemic injury is faster than hypoxic injury
the first effect of hypoxia {decrease in oxygen tention} is on the cell s aerobic respira¬tion as a consequence of reduced oxygen tension, the intracellular generation of atp is markedly reduced. the resulting de¬pletion of atp has widespread effects on many systems
activity of the plasma membrane atp-driven "sodium pump" is reduced. with the subsequent accumulation of intracellular sodium and the diffusion of potassium out of the cell. the net gain of sodium solute is accompa¬nied by an osmotic gain of water, producing acute cellular swelling .