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===[[General Pathology - Necrosis|Necrosis]]===
 
===[[General Pathology - Necrosis|Necrosis]]===
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==Necrosis==
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Necrosis
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The term necrosis means death of cells within the living body.
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Two things happen when necrosis occurs:
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a. further changes can take place in the tissue itself; and
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b. the surrounding unaffected living tissue can react against this necrotic tissue.
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Causes of Necrosis.
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There are three main causes of necrosis:
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1. loss of blood supply - tissues depend upon their blood supply to remain alive,
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2. non-living agents such as chemicals or physical injuries,
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3. living agents such as bacteria, viruses, fungi or parasites.
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1. Loss of blood supply
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.A diminished blood supply to a tissue is called ischaemia. This type of necrosis is called
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ischaemic necrosis, also called infarction - defined as necrosis of a portion of tissue due to
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an interruption (usually sudden) in the blood supply to that portion. The effects of
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ischaemia on a tissue will vary according to:
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a. the type of tissue affected - some tissues are more susceptible than others.
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b. the type of cell in the tissue - the general rule is that parenchymatous cells, the
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essential functioning cells, are more susceptible than the stromal supporting cells.
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c. the metabolic activity of the tissue - very active organs i.e. those that work continuously
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are more susceptible.
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d. whether or not there is a good or potential collateral blood supply
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There are three ways in which tissue ischaemia can be brought about
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a. compression of the blood vessel
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from without e.g. too tight a bandage
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will cause tissue ischaemia. A
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common cause of tissue ischaemia is
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strangulation of the intestine by a
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twist upon itself, or a mass such a
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lipoma ( a relatively common growth
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of mature fat tissue ) forms in the
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mesentery, becomes pedunculated (
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attached by a fine band of the
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mesentery) and can encompass a
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portion of intestine. Initially, the
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compression of the mesenteric veins
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will prevent outflow of blood leading
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to congestion and swelling of the
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affected portion. When the arterial
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supply becomes occluded or cannot
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supply sufficient blood to the tissue
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because of pressure in the swollen
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intestine and its vessels, the affected area undergoes an ischaemic necrosis with disastrous
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sequelae of rupture and peritonitis or gangrene and toxaemia due to absorption of toxic
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products of the necrosis and intestinal bacteria.
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b. a narrowing of the lumen e.g. thickening of the wall in arteriosclerosis.
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c. blocking of the lumen of the vessel, important causes are thrombi and emboli. Renal
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vessels are commonly affected. See the effects of emboli in Circulatory Disorders.
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2. The action of physical or chemical agents.
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The physical agents include burns, cold, frostbite, X-rays, pressure, and actual pinching or
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crushing of the tissue. The necrosis is direct in the case of burns and indirect in the case of
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crushing or pinching which causes occlusion of the vessels supplying the tissue which will
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undergo necrosis. Chemical agents may be directly caustic or corrosive in action or exert
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their effects when absorbed and metabolised to a more toxic substance.
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3. Living agents - their effect is either through their toxic effects on cells or their
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colonisation of the cells.
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Appearance of necrotic lesions
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In a typical necrotic lesion there are three zones.
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1. Where the effect of the causal agent is maximal, there is a sphere of necrosis.
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2. A little further away, the tissue will be damaged but not yet dead, and so there is a
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zone of degeneration short of death.
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3. Still farther away, where the effect of the agent is insufficient to cause death or
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degeneration of cells, we have a zone where the body is reacting to the dead tissue
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Gross and histological features of necrotic tissue.
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1. Colour change in the tissue. In contrast to living tissue, dead tissue tends to be paler,
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partly because there is no circulation in dead tissue
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2. Consistency (texture) of the tissue. The appearance of the centre of the necrotic lesion
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will vary according to the
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1. type of agent responsible and
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2. the tissue in which it is acting.
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This appearance may give a clue to the agent responsible, and the types of necrosis
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encountered are based on their gross description
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a. Coagulation necrosis
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Gross: The necrotic lesion will be
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firmer and dryer on the cut surface. The
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gross appearance still resembles
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somewhat the nearby living tissue. It is
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a feature of bacteria which produce
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toxins, infarction, and some foci of
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viral replication.
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Micro: the general architecture of the
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tissue is preserved. Certain changes
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present can be recognised in an ordinary
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H&E section, and are related to loss of
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cellular detail.
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a. the cells may appear somewhat
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larger and their outline may be lost
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b. the cytoplasm appears structureless
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and homogenous.
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c. there are nuclear changes - the most important
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There are three types of nuclear change.
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i. Pyknosis - Greek for dense - is a
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condition in which the normal nuclear
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structure is replaced by a very dense,
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heavily staining, somewhat smaller angular
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mass of chromatin.
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ii. Karyorrhexis - Greek karyon =
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nucleus; rhexis = breaking up. This
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appearance is rather the reverse of the
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above. It appears as though the nucleus has
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exploded rather than condensed in the
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cytoplasm, and irregular-sized bits of dense
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nuclear material are found scattered
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throughout the centre of the cytoplasm.
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iii. Karyolysis - this means dissolution of the nucleus. The nuclear staining with
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haematoxylin becomes fainter and only the ghost outline of the nucleus remains.
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Apoptosis - is a term used to denote the programmed death of scattered single cells in living
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tissues. Unlike necrosis, there is no reaction to the death of the cell. It is thought that some
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cells are programmed to die - a form of cell regulation in a tissue - unless there is a change in
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circumstances in a tissue that require them to continue living. One such circumstance is the
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development of tumours in which cellular regulation is absent. Cellular apoptosis is thought
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to be important in deleting extra cells produced in embryogenesis, in cyclical physiological
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changes in the genital tract of females, in the death of lymphocytes, in graft rejection, and in
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cellular death by the same injurious substances that cause necrosis in higher doses.
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The cells undergoing
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apoptosis lose their
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connections with their
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neighbours and shrink; the
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nucleus becomes pyknotic;
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and the cytoplasm becomes
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eosinophilic. The cell
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breaks up into fragments
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that are engulfed by
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neighbouring cells or local
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macrophages. Their
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remnants can be seen in the
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neighbouring cells’ cytoplasm.
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b. Liquefactive (Colliquative)
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Necrosis.
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Gross: In the brain where there is a lot of
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lipid, the intracellular enzymatic changes
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make it softer and more fluid in nature. This
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is known as 'malacia'. Initially it becomes
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swollen with a gelatinous, sometimes bloodtinged
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appearance due to disruption of the
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blood vessels but later becomes fluid.
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Micro: the microscopic appearance will
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not resemble the nearby living tissue as it
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may have already lost any semblance of the
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nearby living tissue because it is becoming
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a fluid.
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Another type of liquefactive necrosis,
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quite important is pus formation which
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occurs when the organism causing the initial
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necrosis in the tissue, is capable of attracting
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to the necrotic area large numbers of
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neutrophils and also capable of killing them.
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These are the so-called pyogenic bacteria.
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When the neutrophils die they release
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proteolytic enzymes which digest the dead
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tissue and also more incoming neutrophils.
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The liquid formed is called pus, and it is
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composed mainly of the dead and dying
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neutrophils together with the remnants of
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the necrotic tissue cells.
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In favourable cases, the neutrophils may
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eventually kill the organisms, but in most cases
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the organisms persist, all the time producing
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more pus. This produces an expanding
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sphere of pus that is called an abscess. The
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pressure will build up and if near to the skin
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will cause pressure on the overlying skin, and
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when the pressure is sufficient or the surgeon
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lances it, the abscess will burst discharging the
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pus, and hopefully with it the organisms responsible. This is nature’s way of ridding the body
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of an injurious agent.
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Micro: In the case of an
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abscess, the necrotic area will
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show varying stages of
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degeneration of the
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neutrophils, ranging from
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nearly normal neutrophils, to
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pyknosis, karyorrhexis and
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karyolysis, and finally to a
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homogenous structureless
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admixture of remnants staining
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faintly bluish.
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As this sphere of pus is
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forming, there is a host
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inflammatory response directed against it. This is composed of a capsule of fibrous tissue in
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which there are many blood vessels on its inner surface, which transport the vast number of
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neutrophils into the necrotic centre. This is called the 'pyogenic membrane'. In superficial
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abscesses, when the abscess has discharged to the surface, this membrane can be viewed as a
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crater that has a reddish somewhat ragged lining. Where the abscess is deep within an organ
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such as the liver, there is nowhere to discharge to, and the fibrous capsule around the pus is
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markedly thickened. .
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c. Caseation necrosis.
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The necrotic tissue appears grossly like
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cheese. The colour varies from white to
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grey to yellowish. In sheep it appears
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whitish while in cattle there may be a
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yellowish tinge. The fluid content also
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varies giving a dry crumbling consistency
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in some cases to being more like cottage
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cheese in others. It is really a mixture of
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coagulation and liquefactive necrosis,
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and is a feature of necrosis caused by
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some specific organisms.
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Micro: On histological section, there is a
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complete loss of the architecture, the
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necrotic material being purplish in colour
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due to random intermixing of the
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components that stain with haematoxylin
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and eosin i.e. bits of nuclear material
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interspersed with cytoplasmic fragments.
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This type of necrosis is a feature of
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granulomatous (tumour-like
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proliferation of chronic inflammatory
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cells) processes such as tuberculosis in
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some species, as in the ox, pig and sheep.
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The necrotic tissue is not derived
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principally from the organ in which it
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occurs, but from a special type of host
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inflammatory cell - the macrophage -
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which is sent into the tissue in large
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numbers to engulf the organism. The
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organism has defences against the enzymes of the macrophages and is quite willing to
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continue to grow and multiply within these macrophages eventually causing their death. In
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some granulomas, the macrophages will combine together and form giant cells.
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Fungi and parasites also cause granulomas.
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Calcification. In the condition of calcification, calcium salts are deposited within the
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necrotic tissue in an effort to make it more inert. It is seen quite commonly in necrosis in
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cattle and sheep, and is a common feature in lesions which show caseation necrosis, and
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usually indicates a lesion of long standing. Such calcified necrotic tissue can be appreciated
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grossly. The deposits of calcium salts can be palpated and on cutting into the necrotic
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portion, the calcified material may be both felt as a gritty substance and heard by a grating
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sound against the knife.
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The colour is usually chalk-white but may have a yellowish green tinge if the inciting cause
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is a parasite. Parasites attract a large number of eosinophils that are responsible for this
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colour. This type of calcium deposition in necrotic tissue is called dystrophic calcification.
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It is an attempt to make the tissue more inert. It does not result from elevated levels of
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calcium in the blood.
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Micro: In sections stained by H&E, calcium has a
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distinctive dark blue colour. You may also see some
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shattering of the calcium and adjacent tissue due to the
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effect of the microtome knife
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passing through it. It blunts the knife and there may be
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score marks throughout the rest of the section. Difficulty
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sometimes arises in distinguishing calcium from
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bacterial colonies that stain a similar colour. A
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definitive special stain for calcium is to stain the
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section with silver nitrate (the von Kossa method).
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The calcium stains black.
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Sequel to necrosis
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These will vary in relation to the causes of necrosis, but by and large it is important to
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distinguish between dead tissue on the surface of the body and dead tissue in the depths of
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the body; a piece of dead skin as compared with a portion of dead liver.
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Dead tissue on the surface can be shed and is said to slough, whereas dead tissue in the centre
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of the liver cannot naturally be shed from the surface. Something else happens to it. It can
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either be absorbed or replaced by fibrous tissue, or it can be enclosed by fibrous tissue. This
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is part of the process of inflammation - the response of the body to local injury. It is a
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general rule that small areas of necrosis become absorbed and replaced by fibrous tissue
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(scars) while larger areas become encapsulated by fibrous tissue, the necrotic portion
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remaining in the centre. This effectively cuts off any contact with living tissue, and allows
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perhaps further changes to occur within the necrotic portion to make it more inert. The
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encapsulated portion is called a sequestrum. It can be, as mentioned before, be calcified to
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make it more inert.
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When necrosis occurs on an epithelial surface, two things may happen depending upon the
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depth of the necrosis. In a case like 'Foot and Mouth' where the necrosis is confined to the
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middle and outer layers of the epithelium, the remaining underlying germinal layer divides
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and replaces the shed portion. This type of necrosis confined to the epithelium is called an
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erosion. It leaves no scar.
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When the necrosis extends below the basement membrane of the epithelium as might be
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caused by an applied corrosive substance or a burn, the body reacts to this interruption in the
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integrity of the epithelium with an underlying inflammatory reaction attempting to repair the
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deficit by fibrous tissue. This type of necrosis is called ulceration, and the resultant
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contraction of the fibrous tissue leaves a scar.
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Fat necrosis
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This is confined to the fat depots of the body.
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It has a very distinctive appearance grossly: instead
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of the fat being semi- translucent and malleable, it
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shows areas of focal opacity and is very hard in
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consistency. This appearance is due to the
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intracellular fat after the fat cells have died, being
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broken down into fatty acids which combine with
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Ca++, Na+ and K+ ions to forms soaps. These soaps
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are substances foreign to the body and they provoke a
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host inflammatory response. Unlike fat, they do not
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dissolve out in routine preparation of sections,
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These areas of fat necrosis remain indefinitely, may
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show great scarring, and quite often calcify. It occurs
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principally in two ways in the body.
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a. Enzymatic necrosis of fat. This happens when there is a release of pancreatic enzymes
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into the neighbouring mesenteric fat, the release being caused by a damaged pancreas e.g.
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due to an adjacent tumour.
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b. Traumatic necrosis of fat. This is seen in the
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subcutaneous tissue following trauma to the area.
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It is quite common in the brisket of recumbent
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animals due to the prolonged pressure on the area.
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It is worth mentioning here another condition of fat that can also undergo necrosis and
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calcify. This is the so-called lipomatosis that occurs for some unknown reason in Channel
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Island breeds of cattle. In this condition, there are focal areas of increased fat in the
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mesentery. They often surround several loops of the gut, and if they become necrotic, they
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may strangle the enclosed gut with disastrous consequences for the animal.'
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Gangrene
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Gangrene is a post-necrotic change, and in some cases is the ultimate degradation of necrotic
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tissue. The tissue is already dead. There are two main types
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a. Wet gangrene - life threatening
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b. Dry gangrene - non life threatening
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a. Wet gangrene can either be due to:
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a. the agent which initially kills the tissue, further putrefying it, or
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b. the gangrene may be due to dead tissue killed by some other means being invaded by
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organisms which putrefy it.
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In other words the former may be viewed as a primary gangrene, while the latter is
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secondary.
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An example of the former is gangrenous mastitis of the udder of the cow caused by
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Staphylococcus aureus, the organism killing the tissue and then putrefying it.
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An example of secondary gangrene is that which occurs when a portion of gut twists on its
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mesentery or when a lipomatous mass attached to a strand of mesentery, loops around a piece
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of intestine as depicted earlier with regard to tissue ischaemia. The blood supply to the gut is
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cut off, and the affected portion becomes necrotic. Wet gangrene supervenes when the
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putrefactive organisms that are normally present in the gut invade the dead tissue.
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A further cause of wet gangrene is when a ligature around an extremity causes ischaemic
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necrosis of tissue distal to it and the necrotic tissue becomes invaded with putrefactive
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bacteria.
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The gross appearance is of a swollen puffy tissue cold to the touch and with a horrible smell
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owing to the hydrogen sulphide (the smell of rotting flesh) produced in the putrefying tissue.
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In comparison to other dead tissue the zone of inflammation between the dead putrefying
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tissue and living tissue is indistinct. This type of gangrene is overwhelming disastrous for the
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animal unless treated quickly and effectively, as the organisms produce potent toxins either
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themselves or in their breakdown of the dead tissue and the animal rapidly succumbs to
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toxaemia.
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A variation of wet gangrene is that produced by Clostridia organisms such as Clostridium
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chauvei and C. septicum whereby they also form gas. This is called gas gangrene. The
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conditions of Blackleg and Clostridia contamination of wounds produce this type of
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gangrene.
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Dry gangrene, on the other hand, is not life threatening. This is really mummification
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(like an Egyptian mummy) of an extremity, such as the tail, foot or ears of animals. There is
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an occlusion of the blood supply to the extremity. The tissue becomes necrotic.
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Because of air circulating around the extremity, water is drawn out of the tissue, drying and
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preserving it. There is little if any bacterial growth in the tissue and it eventually sloughs off.
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In small animals crushing of the tail may cause this by cutting off the blood supply.
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In large animals, it is seen commonly following a septicaemic condition in which bacteria
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are growing and passing around in the circulation. An embolus blocks the blood supply.
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When seen in calves, the possibility of Salmonellosis must be kept in mind. Other causes
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are frostbite and ergot poisoning.
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Finally, necrosis is irreversible.
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===Causes of Necrosis===
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===Gross and Histological Features of Necrotic Lesions===
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====Coagulation Necrosis====
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====Liquefactive Necrosis====
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====Caseation Necrosis====
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===Sequel to Necrosis===
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====Fat Necrosis====
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====Gangrene====
      
==Post Mortem Change==
 
==Post Mortem Change==
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