Free radicals in critical ill patient

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Free radicals in critical ill patient

• Oxygen free radicals are byproducts from the
  fundamental metabolic activities within the body.
• Normally, radicals are neutralized by enzymatic
  activity or natural antioxidants.
• Dependence on balance between oxygen radical
  production and eradication.

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Free radicals in critical ill patient

• Molecular oxygen is used primarily in the
  production of cellular energy through the
  synthesis of ATP by oxidative phosphorylation,
  the transfer of electrons from on molecule to
  another.
• A byproduct of energy generation is the formation
  of free radicalsany atom or molecule with an
  unpaired electron in its outer obit.

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Free radicals in critical ill patient

• In aerobic metabolism, oxygen reacts with many
  different molecules, producing oxygen
  radicals---oxygen assists in the transfer of
  electron from one molecule to the other.

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Free radicals in critical ill patient
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Free radicals in critical ill patient
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Free radicals in critical ill patient

• Oxygen free radicals affect cells by three
  mechanisms
• 1gt initiate a single reaction
• 2gt start a chain reaction
• 3gt the branching reaction---is the most
  destructive.

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Free radicals in critical ill patient

• Oxygen free radical are a byproduct of many
  normal reactions within the body
• --energy generation
• --breakdown of lipids and proteins
• --catecholamine responses
• --inflammatory process

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Free radicals in critical ill patient

• Other normal mechanisms within the body that
  produce oxygen free radicals
• --neutrophil activity
• --phospholipase release
• --arachidonic acid oxidation
• --after ischemia/reperfusion

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Free radicals in critical ill patient

• The oxygen free radical,bulletOH, causes the
  most damage because it is able to attach to ,or
  transfer electrons form, almost all compounds.
• The type of damage that occurs from the hydroxyl
  radical depend on what structures it is near at
  the time it is produced.

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Free radicals in critical ill patient
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Free radicals in critical ill patient
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Free radicals in critical ill patient
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Free radicals in critical ill patient
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Free radicals in critical ill patient

• Carcinogenesis--radiation exposure is a
  carcinogen radiation splits the oxygen and
  hydrogen bound in water into H and OH-. OH has
  been identified as the most reactive free
  radical. --OH causes a series of chain reactions
  that can alter the DNA structure of cells(strand
  scission).

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Free radicals in critical ill patient

• Atherosclerosis--If LDL is oxidized in the
  artery wall by oxygen free radicals, the
  structure of LDL is modified and must be
  recognized by a different set of receptors on the
  macrophages. This new set of macrophage receptors
  more efficiently engulfs LDL, resulting in an
  increased accumulation of cholesterol.

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Free radicals in critical ill patient

• Head Injury--Oxygen free radicals may be a
  primary culprit in the damage that occurs to
  brain tissue when ischemia is of a relatively
  long duration, when oxygen continues to be
  delivered to the ischemic tissue, and when tissue
  that has been deprived of oxygen is reperfused.

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Free radicals in critical ill patient

• Ischemia-reperfusion injury--evidence exists
  that reperfusion of an injured area increases
  formation of oxygen free radicals secondary to
  injury.--reperfusion injury is believed to occur
  not from ischemia but after ischemic injury as a
  result of the reintroduction of oxygen of the
  injured area.

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Free radicals in critical ill patient
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Free radicals in critical ill patient

• Antioxidants are physiologic substances that
  protect the body against damage from chemical
  reactions caused by oxygen free radicals.
• An antioxidant works by stopping the chain
  reaction caused by free radicals, by either
  removing free oxygen radicals, preventing their
  formation, or repairing the damage they cause in
  cell structure.

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Free radicals in critical ill patient

• Several types of antioxidants currently used in
  clinical trials1gt naturally in the body
  (alpha-tocopherol, glutathione, superoxide
  dismutase)2gt synthetic antioxidants that act
  against iron-dependent free radical
  reactions(probucol)3gt pharmocologic agents used
  for other clinical applications that have
  antioxidant properties(21 aminosteroids)

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Free radicals in critical ill patient

• Naturrally occurring antioxidantsSuperoxide
  dismutase(SOD) 1969, is produced in two forms in
  the body (1) the mitochondria accommodates
  manganese SOD, and (2) copper/zinc SOD dwells
  within cellular cytoplasma.--The antioxidant
  properties of both forms of SOD include
  protection of tissue from damage by
  oxygen-derived free radicals generated during
  periods of ischemia.

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Superoxide dismutase(SOD)

• The action of SOD transforms superoxide radical
  into the more stable hydrogen peroxide, which
  eventually is transformed into water and harmless
  oxygen.
• SOD is being tested for usefulness in preventing
  rejection in donor organ tissue injury, in
  minimizing the extent of injury after trauma, and
  in premature neonates less than 1500 gm.

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Free radicals in critical ill patient

• Naturally occurring antioxidantsAlpha-tocopherol
  (vitamin E)--It is lipid soluble and transforms
  oxygen free radicals to a nonreactive vitamin E
  radical primarily within lipoprotein and
  membranes.--By preventing LDL oxidation and the
  breakdown of the cellular structures, vitamin E
  could obstruct formation of toxic oxidative
  processed and thus break the peroxidation chain.

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Free radicals in critical ill patient

• Synthetic antioxidantsProbucol
• --It is a synthetic cholesterol-lowering agent.
• --It decreases serum cholesterol and LDL directly
  and also play a role in preventing the
  development of atherosclerotic lesions through
  its antioxidant properties.

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Probucol

• It inhibits atherosclerosis by prohibiting
  iron-dependent, oxygen free radical production
  avoiding oxidation of lipids in the blood and
  lessening uptake cholesterol by LDL receptive
  macrophages.

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Free radicals in critical ill patient

• Synthetic antioxidants
• Aminosteroids
• --a synthetic family of corticosteroids is
  structurally similar to the mineraloglucocorticoid
  steroid methylprednisolone, and is being
  manufactured and tested as an antioxidant.
• --These drugs are able to cross the blood brain
  barrier, penetrate cell membranes, and protect
  cell stuctures from free radical attack.

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Free radicals in critical ill patient
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Free radicals in critical ill patient