Ischemic cell death

Ischemic cell death, or oncosis, is a form of accidental cell death. The process is characterized by an ATP depletion within the cell leading to impairment of ionic pumps, cell swelling, clearing of the cytosol, dilation of the Endoplasmic Reticulum and Golgi, mitochondrial condensation, chromatin clumping, and cytoplasmic bleb formation.[1] Oncosis refers to a series of cellular reactions following injury that precedes cell death. The process of oncosis is divided into three stages. First, the cell becomes committed to oncosis as a result of damage incurred to the plasma membrane through toxicity or ischemia, resulting in the leak of ions and water due to ATP depletion.[2] The ionic imbalance that occurs subsequently causes the cell to swell without a concurrent change in membrane permeability to reverse the swelling.[3] Stage two the reversibility threshold for the cell is passed and it becomes committed to cell death. During this stage the membrane becomes abnormally permeable to trypan blue and propidium iodide, indicating membrane compromise.[4] The final stage is cell death and removal of the cell via phagocytosis mediated by an inflammatory response.[5]

Etymology

Although ischemic cell death is the accepted name of the process, the alternative name of oncosis was introduced as the process involves the affected cell(s) swelling to an abnormally large size in known models. This is thought to be caused by failure of the plasma membrane's ionic pumps. The name oncosis (derived from ónkos, meaning largeness, and ónkosis, meaning swelling) was first introduced in 1910 by pathologist Friedrich Daniel von Recklinghausen.[6]

Comparison to Apoptosis

Oncosis and apoptosis are distinct processes of cellular death. Oncosis is characterized by cellular swelling caused by a failure in ion pump function. Apoptosis, or programmed cell death involves a series of cell shrinking processes, beginning with cell size reduction and pyknosis, followed by cell budding and karyorrhexis, and phagocytosis by macrophages or neighboring cells due to size decrease.[7] The phagocytic disposal of apoptotic cells prevents the release of cellular debris that could induce an inflammatory response in neighboring cells.[8] In opposition, the leakage of cellular content associated with membrane disruption in oncosis often incites an inflammatory response in neighboring tissue, causing further cellular injury.[9] Additionally, apoptosis and the degradation of intracellular organelles is mediated by caspase activation, particularly caspase-3.[10] Oligonuclosomal DNA fragmentation is initiated by caspase-activated deoxyribonuclease following caspase-3 mediated cleavage of the enzyme’s inhibitor, ICAD.[11] In contrast, the oncotic pathway has been shown to be caspase-3 independent.[12]

The primary determinant of cell death occurring via the oncotic or apoptotic pathway is cellular ATP levels.[13] Apoptosis is contingent upon ATP levels to form the energy dependent apoptosome.[14] A distinct biochemical event only seen in oncosis is the rapid depletion of intracellular ATP.[15] The lack of intracellular ATP results in a deactivation of sodium and potassium ATPase within the compromised cell membrane.[16] The lack of ion transport at the cell membrane leads to an accumulation of sodium and chloride ions within the cell with a concurrent water influx, contributing to the hallmark cellular swelling of oncosis.[17] As with apoptosis, oncosis has been shown to be genetically programmed and dependent on expression levels of uncoupling protein-2 (UCP-2) in HeLa cells. An increase in UCP-2 levels leads to a rapid decrease in mitochondrial membrane potential, reducing mitochondrial NADH and intracellular ATP levels, initiating the oncotic pathway.[18] The anti-apoptotic gene product Bcl-2 is not an active inhibitor of UCP-2 initiated cell death, further distinguishing oncosis and apoptosis as distinct cellular death mechanisms.[19]

References

  1. ^ Weerasinghe, Priya, and L. Maximilian Buja. "Oncosis: an important non-apoptotic mode of cell death." Experimental and molecular pathology 93.3 (2012): 302-308.
  2. ^ Weerasinghe, Priya, and L. Maximilian Buja. "Oncosis: an important non-apoptotic mode of cell death." Experimental and molecular pathology 93.3 (2012): 302-308.
  3. ^ Weerasinghe, Priya, and L. Maximilian Buja. "Oncosis: an important non-apoptotic mode of cell death." Experimental and molecular pathology 93.3 (2012): 302-308.
  4. ^ Weerasinghe, Priya, and L. Maximilian Buja. "Oncosis: an important non-apoptotic mode of cell death." Experimental and molecular pathology 93.3 (2012): 302-308.
  5. ^ Scarabelli, T. M., Knight, R., Stephanou, A., Townsend, P., Chen-Scarabelli, C., Lawrence, K., Gottlieb, R., Latchman, D., & Narula, J. (2006). Clinical implications of apoptosis in ischemic myocardium. Current problems in cardiology, 31(3), 181-264.
  6. ^ Majno; Joris (1995). "Apoptosis, oncosis, and necrosis. An overview of cell death". Am. J. Pathol. 146 (1): 1–2, 16–19. PMC 1870771. PMID 7856735.
  7. ^ Majno, G., & Joris, I. (1995). Apoptosis, oncosis, and necrosis. An overview of cell death. The American journal of pathology, 146(1), 3.
  8. ^ Ren, Y., & Savill, J. (1998). Apoptosis: the importance of being eaten. Cell Death & Differentiation, 5(7), 563-568.
  9. ^ Ren, Y., & Savill, J. (1998). Apoptosis: the importance of being eaten. Cell Death & Differentiation, 5(7), 563-568.
  10. ^ Earnshaw, W. C., Martins, L. M., & Kaufmann, S. H. (1999). Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annual review of biochemistry, 68(1), 383-424.
  11. ^ Enari, M., Sakahira, H., Yokoyama, H., Okawa, K., Iwamatsu, A., & Nagata, S. (1998). A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature, 391(6662), 43-50.
  12. ^ Weerasinghe, Priya, and L. Maximilian Buja. "Oncosis: an important non-apoptotic mode of cell death." Experimental and molecular pathology 93.3 (2012): 302-308.
  13. ^ Eguchi Y, Shimizu S and Tsujimoto Y (1997) Intracellular ATP levels determine cell death fate by apoptosis or necrosis. Cancer Res. in press
  14. ^ Eguchi Y, Shimizu S and Tsujimoto Y (1997) Intracellular ATP levels determine cell death fate by apoptosis or necrosis. Cancer Res. in press
  15. ^ Yamamoto, N., Smith, M. W., Maki, A., Berezesky, I. K., & Trump, B. F. (1994). Role of cytosolic Ca2+ and protein kinases in the induction of the hsp70 gene. Kidney International, 45(4), 1093-1104.
  16. ^ Yamamoto, N., Smith, M. W., Maki, A., Berezesky, I. K., & Trump, B. F. (1994). Role of cytosolic Ca2+ and protein kinases in the induction of the hsp70 gene. Kidney International, 45(4), 1093-1104.
  17. ^ Yamamoto, N., Smith, M. W., Maki, A., Berezesky, I. K., & Trump, B. F. (1994). Role of cytosolic Ca2+ and protein kinases in the induction of the hsp70 gene. Kidney International, 45(4), 1093-1104.
  18. ^ Mills, E. M., Xu, D., Fergusson, M. M., Combs, C. A., Xu, Y., & Finkel, T. (2002). Regulation of cellular oncosis by uncoupling protein 2. Journal of Biological Chemistry, 277(30), 27385-27392.
  19. ^ Mills, E. M., Xu, D., Fergusson, M. M., Combs, C. A., Xu, Y., & Finkel, T. (2002). Regulation of cellular oncosis by uncoupling protein 2. Journal of Biological Chemistry, 277(30), 27385-27392.
Algor mortis

Algor mortis (Latin: algor—coldness; mortis—of death), the second stage of death, is the change in body temperature post mortem, until the ambient temperature is matched. This is generally a steady decline, although if the ambient temperature is above the body temperature (such as in a hot desert), the change in temperature will be positive, as the (relatively) cooler body acclimates to the warmer environment. External factors can have a significant influence.

The term was first used by Dowler in 1849. The first published measurements of the intervals of temperature after death were done by Dr John Davey in 1839.

Cell death

Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, or may result from such factors as disease, localized injury, or the death of the organism of which the cells are part. Apoptosis or Type I cell-death, and autophagy or Type II cell-death are both forms of programmed cell death, while necrosis is a non-physiological process that occurs as a result of infection or injury.

Dead on arrival

Dead on arrival (DOA), also dead in the field and brought in dead (BID), indicates that a patient was found to be already clinically dead upon the arrival of professional medical assistance, often in the form of first responders such as emergency medical technicians, paramedics, or police.

In some jurisdictions, first responders must consult verbally with a physician before officially pronouncing a patient deceased, but once cardiopulmonary resuscitation is initiated, it must be continued until a physician can pronounce the patient dead.

Death hoax

A death hoax is a deliberate or confused report of someone's death that turns out to be incorrect and murder rumors. In some cases it might be because the person has intentionally faked death.

Death messenger

Death messengers, in former times, were those who were dispatched to spread the news that an inhabitant of their city or village had died. They were to wear unadorned black and go door to door with the message, "You are asked to attend the funeral of the departed __________ at (time, date, and place)." This was all they were allowed to say, and were to move on to the next house immediately after uttering the announcement. This tradition persisted in some areas to as late as the mid-19th century.

Death rattle

Terminal respiratory secretions (or simply terminal secretions), known colloquially as a death rattle, are sounds often produced by someone who is near death as a result of fluids such as saliva and bronchial secretions accumulating in the throat and upper chest. Those who are dying may lose their ability to swallow and may have increased production of bronchial secretions, resulting in such an accumulation. Usually, two or three days earlier, the symptoms of approaching death can be observed as saliva accumulates in the throat, making it very difficult to take even a spoonful of water. Related symptoms can include shortness of breath and rapid chest movement. While death rattle is a strong indication that someone is near death, it can also be produced by other problems that cause interference with the swallowing reflex, such as brain injuries.It is sometimes misinterpreted as the sound of the person choking to death, or alternatively, that they are gargling.

Death trajectory

Death trajectory refers to the pattern of dying when a patient is given a projected death date with limited or no medical recourse for the remaining existence of the individual's life. The death trajectory is dependent on the cause of death, whether it is sudden death, chronic illness, or the steady decline in health due to senescence (aging). Death trajectory is analyzed in two separate aspects: duration and shape. Duration refers to the period of time a patient has to live, which can be anywhere from imminent death to several months. Shape refers to how that duration is then graphed. In other words, the shape is "the course of dying, its predictability, and whether death is expected or unexpected".

Dying trajectories were first studied in the 1960s by two researchers, Barney Glaser and Anselm Strauss, in an attempt to understand the end of human life from different ailments, including cancer.

Dignified death

Dignified death is a somewhat elusive concept often related to suicide. One factor that has been cited as a core component of dignified death is maintaining a sense of control. Another view is that a truly dignified death is an extension of a dignified life. There is some concern that assisted suicide does not guarantee a dignified death, since some patients may experience complications such as nausea and vomiting. There is some concern that age discrimination denies the elderly a dignified death.

Dysthanasia

In medicine, dysthanasia means "bad death" and is considered a common fault of modern medicine.Dysthanasia occurs when a person who is dying has their biological life extended through technological means without regard to the person's quality of life. Technologies such as an implantable cardioverter defibrillator, artificial ventilation, ventricular assist devices, and extracorporeal membrane oxygenation can extend the dying process.

Dysthanasia is a term generally used when a person is seen to be kept alive artificially in a condition where, otherwise, they cannot survive; sometimes for some sort of ulterior motive. The term was used frequently in the investigation into the death of Formula One driver Ayrton Senna in 1994.

Lazarus sign

The Lazarus sign or Lazarus reflex is a reflex movement in brain-dead or brainstem failure patients, which causes them to briefly raise their arms and drop them crossed on their chests (in a position similar to some Egyptian mummies). The phenomenon is named after the Biblical figure Lazarus of Bethany, whom Jesus raised from the dead in the Gospel of John.

Megadeath

Megadeath (or megacorpse) is one million human deaths, usually caused by a nuclear explosion. The term was used by scientists and thinkers who strategized likely outcomes of all-out nuclear warfare.

Mortality displacement

Mortality displacement denotes a temporary increase in the mortality rate (number of deaths) in a given population, also known as excess mortality or excess mortality rate. It is usually attributable to environmental phenomena such as heat waves, cold spells, epidemics and pandemics, especially influenza pandemics, famine or war.

During heat waves, for instance, there are often additional deaths observed in the population, affecting especially older adults and those who are sick. After some periods with excess mortality, however, there has also been observed a decrease in overall mortality during the subsequent weeks. Such short-term forward shift in mortality rate is also referred to as harvesting effect. The subsequent, compensatory reduction in mortality suggests that the heat wave had affected especially those whose health is already so compromised that they "would have died in the short term anyway".Death marches can also lead to a significant mortality displacement, such as in the Expulsion of the Valencian Moriscos in 1609 throughout the Kingdom of Valencia and Spanish-held Algeria, the American Indian Trail of Tears, the Armenian Genocide, and the Bataan death march, wherein the oldest, weakest, and sickest died first.

Necronym

A necronym (from the Greek words νεκρός, nekros, "dead" and ὄνομα ónoma, "name") is a reference to, or name of, a person who has died. Many cultures have taboos and traditions associated with referring to such a person. These vary from the extreme of never again speaking the person's real name, often using some circumlocution instead, to the opposite extreme of commemorating it incessantly by naming other things or people after the deceased.

For instance, in some cultures it is common for a newborn child to receive the name (a necronym) of a relative who has recently died, while in others to reuse such a name would be considered extremely inappropriate or even forbidden. While this varies from culture to culture, the use of necronyms is quite common.

Necrophobia

Necrophobia is a specific phobia which is the irrational fear of dead things (e.g., corpses) as well as things associated with death (e.g., coffins, tombstones, funerals, cemeteries). With all types of emotions, obsession with death becomes evident in both fascination and objectification. In a cultural sense, necrophobia may also be used to mean a fear of the dead by a cultural group, e.g., a belief that the spirits of the dead will return to haunt the living.Symptoms include: shortness of breath, rapid breathing, irregular heartbeat, sweating, dry mouth and shaking, feeling sick and uneasy, psychological instability, and an altogether feeling of dread and trepidation. The sufferer may feel this phobia all the time. The sufferer may also experience this sensation when something triggers the fear, like a close encounter with a dead animal or the funeral of a loved one or friend. The fear may have developed when a person witnessed a death, or was forced to attend a funeral as a child. Some people experience this after viewing frightening media.The fear can manifest itself as a serious condition. Treatment options include medication and therapy.The word necrophobia is derived from the Greek nekros (νεκρός) for "corpse" and the Greek phobos (φόβος) for "fear".

Obituary

An obituary (obit for short) is a news article that reports the recent death of a person, typically along with an account of the person's life and information about the upcoming funeral. In large cities and larger newspapers, obituaries are written only for people considered significant. In local newspapers, an obituary may be published for any local resident upon death. A necrology is a register or list of records of the deaths of people related to a particular organization, group or field, which may only contain the sparsest details, or small obituaries. Historical necrologies can be important sources of information.

Two types of paid advertisements are related to obituaries. One, known as a death notice, omits most biographical details and may be a legally required public notice under some circumstances. The other type, a paid memorial advertisement, is usually written by family members or friends, perhaps with assistance from a funeral home. Both types of paid advertisements are usually run as classified advertisements.

Pallor mortis

Pallor mortis (Latin: pallor "paleness", mortis "of death"), the first stage of death, is an after-death paleness that occurs in those with light/white skin.

Post-mortem interval

Post-mortem interval (PMI) is the time that has elapsed since a person has died. If the time in question is not known, a number of medical/scientific techniques are used to determine it. This also can refer to the stage of decomposition of the body.

Promession

Promession is an idea of how to dispose human remains by way of freeze drying. The concept of promession was developed by Swedish biologist Susanne Wiigh-Mäsak, who derived the name from the Italian word for "promise" (promessa). She founded Promessa Organic AB in 1997 to commercially pursue her idea. The company was liquidated 2015 without being able to produce a functioning facility. The idea of promession is questioned and not a functional method according to critics.

Skeletonization

Skeletonization refers to the final stage of decomposition, during which the last vestiges of the soft tissues of a corpse or carcass have decayed or dried to the point that the skeleton is exposed. By the end of the skeletonization process, all soft tissue will have been eliminated, leaving only disarticulated bones. In a temperate climate, it usually requires three weeks to several years for a body to completely decompose into a skeleton, depending on factors such as temperature, humidity, presence of insects, and submergence in a substrate such as water. In tropical climates, skeletonization can occur in weeks, while in tundra areas, skeletonization may take years or may never occur, if subzero temperatures persist. Natural embalming processes in peat bogs or salt deserts can delay the process indefinitely, sometimes resulting in natural mummification.The rate of skeletonization and the present condition of a corpse or carcass can be used to determine the time of death.After skeletonization, if scavenging animals do not destroy or remove the bones, acids in many fertile soils take about 20 years to completely dissolve the skeleton of mid- to large-size mammals, such as humans, leaving no trace of the organism. In neutral-pH soil or sand, the skeleton can persist for hundreds of years before it finally disintegrates. Alternately, especially in very fine, dry, salty, anoxic, or mildly alkaline soils, bones may undergo fossilization, converting into minerals that may persist indefinitely.

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