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New page: {{review}} {{toplink |linkpage =General Pathology |linktext =General Pathology |maplink = General Pathology (Content Map) |pagetype =Pathology }} <br> ==Introduction== * '''Necrosis''' me...
{{review}}
{{toplink
|linkpage =General Pathology
|linktext =General Pathology
|maplink = General Pathology (Content Map)
|pagetype =Pathology
}}
<br>
==Introduction==
* '''Necrosis''' means the death of cells within the living body.
* Two things happen when necrosis occurs:
*# Further changes can take place in the tissue itself.
*# The surrounding unaffected living tissue can react against this necrotic tissue.
==Causes of Necrosis==
* There are three main causes of necrosis:
*# Loss of blood supply.
*#* Tissues depend upon their blood supply to remain alive.
*# Non-living agents such as chemicals or physical injuries.
*# Living agents such as [[Bacteria|bacteria]], [[Viruses|viruses]], [[Fungi|fungi]] or [[Parasites|parasites]].
===Loss of Blood Supply===
* Necrosis due to interuption of blood supply to a portion of tissue is known as '''ischaemic necrosis''', or [[Ischaemia and Infarction - Pathology#Infarction|'''infarction''']].
* The effects of [[Ischaemia and Infarction - Pathology#Ischaemia|ischaemia]] on a tissue vary according to:
** The tissue affected.
*** Some tissues are more susceptible than others.
** The type of cell in the tissue.
*** Generally, parenchymatous (functioning) cells are more susceptible than the stromal supporting cells.
** The metabolic activity of the tissue.
*** Very active organs are more susceptible.
** Whether there is a good or potential collateral blood supply.
* Tissue [[Ischaemia and Infarction - Pathology#Ischaemia|ischamia]] can be brought about in three ways:
** Compression of the blood vessel.
** Narrowing of the lumen.
** Blocking of the lumen .
====Compression of the Blood Vessel====
* A common cause of tissue ischaemia is [[Intestine Physical Disturbances - Pathology#Positional Changes/ Displacements|strangulation of the intestine]] by a twist upon itself.
** Compression of the mesenteric veins prevents outflow of blood
*** The affected portion becomes congested and swollen.
** The arterial supply cannot supply sufficient blood because of pressure in the swollen intestine and its vessels.
*** The affected area undergoes an ischaemic necrosis.
**** Sequelae include
***** Rupture and peritonitis
***** [[Necrosis - Pathology#Gangrene|Gangrene]] and toxaemia
****** Due to absorption of toxic products of the necrosis and intestinal bacteria.
* Another cause is a mass, such a lipoma, forming in the mesentery
** Becomes pedunculated (attached by a fine band of the mesentery).
*** Can encompass and strangulate a portion of intestine.
====Narrowing of the Lumen====
* E.g. thickening of the wall in arteriosclerosis.
====Blocking of the Lumen====
* Important causes are [[Thrombosis - Pathology#Introduction|thrombi]] and [[Thrombosis - Pathology#Embolism|emboli]].
* Renal vessels are commonly affected.
===Physical or Chemical Agents===
====Physical Agents====
* Include:
** Burns
** Cold
** Frostbite
** X-rays
** Pressure
** Pinching or crushing of the tissue.
* Necrosis my be:
** Direct
*** E.g. in the case of burns.
** Indirect
*** E.g. in crushing or pinching.
*** Vessels supplying the tissue are occluded, leading to necrosis of the tissue.
====Chemical Agents====
* May be directly caustic or corrosive in action.
* May exert their effects when absorbed and metabolised to a more toxic substance.
===Living agents===
* Living agents exert their effects though either
** Their toxic effects on cells, or
** Their colonisation of the cells.
==Appearance of Necrotic Lesions==
* There are three zones in a typical necrotic lesion.
*# There is a sphere of necrosis where the effect of the causal agent is maximal.
*# A little further away there is a zone where the tissue is damaged, but not yet dead.
*# Still farther away, the effect of the agent is insufficient to cause death or degeneration of cells.
*#* There is a zone where the body is reacting to the dead tissue.
===Gross and Histological Features of Necrotic Tissue===
* A change in colour is seen in necrotic tissue,
** Dead tissue tends to be paler than live tissue.
*** This is partly because there is no circulation.
* There is also a change in the consistency of the tissue.
*The appearance of the centre of the necrotic lesion varies according to:
*# The type of agent responsible
*# The tissue in which the agent is acting.
** This appearance may give a clue to the agent responsible.
==Types of Necrosis==
* The types of necrosis encountered are based on their gross description.
===Coagulation Necrosis===
* Coagulation necrosis is a feature of:
** Bacteria which produce toxins
** Infarction
** Some foci of viral replication.
=====Gross=====
* The necrotic lesion is firmer and dryer on the cut surface. The
* There is some resemblance to the nearby living tissue.
=====Histological=====
[[Image:coagulative_necrosis.jpg|right|thumb|100px|<small><center>Renal infarct - Coagulative Necrosis(Courtesy of S. Rhind)</center></small>]]
* The general architecture of the tissue is preserved.
* Certain changes related to loss of cellular detail can be recognised in an ordinary H&E section.
** Cells may appear larger and their outline may be lost
** Cytoplasm appears structureless and homogenous.
** There are '''nuclear changes'''
*** This is the most important feature.
* There are '''three types''' of '''nuclear change'''.
*# '''Pyknosis'''
*#* Greek for dense.
*#* The normal nuclear structure is replaced by a very dense, heavily staining, smaller, angular mass of chromatin.
*# '''Karyorrhexis'''
*#* This is from the Greek:
*#** karyon = nucleus
*#** rhexis = breaking up
*#* The nucleus appears as though it has exploded rather than condensed.
*#** Irregular-sized bits of dense nuclear material are found scattered throughout the centre of the cytoplasm.
*#** A kind of "reverse appearance" to pyknosis.
*# '''Karyolysis'''
*#* Karyolysis means dissolution of the nucleus.
*#* The nucleus is more faintly stained with haematoxylin.
*#** Only the ghost outline of the nucleus remains.
===Liquefactive Necrosis===
====Malacia====
* This is liquefactive necrosis in the brain.
* There is a lot of lipid in the brain.
** The intracellular enzymatic changes involved in necrosis make this softer and more fluid.
* Initially the affected area becomes swollen and gelatinous.
** Is sometimes bloodtinged due to disruption of the blood vessels.
**Later the area becomes fluid.
* The microscopic appearance does not resemble the nearby living tissue.
** The tissue is becoming a fluid.
====Pus Formation====
* Occurs when the organism causing the initial necrosis in the tissue is capable of attracting and killing large numbers of [[Neutrophils - WikiBlood|neutrophils]].
** I.e the '''pyogenic bacteria'''.
* [[Neutrophils - WikiBlood|Neutrophils]] release proteolytic enzymes when they die.
** These digest the dead tissue and also more incoming neutrophils.
*** The liquid formed is called '''pus'''.
* Pus is mainly composed of dead and dying neutrophils .
** Also contains the remnants of the necrotic tissue cells.
* Although in favourable cases the neutrophils may eventually kill the organisms, in most cases the organisms persist, producing more pus.
** Produces an expanding sphere of pus known as an [[Acute Inflammation - Pathology#Purulent|'''abscess''']].
*** If the abscess is near to the skin and pressure becomes sufficient after build up, it will burst.
**** Pus is discharged, hopefully along with the organisms responsible.
**** This is nature's way of ridding the body of an injurious agent.
=====Histological Appearance of an Abscess=====
* The necrotic area shows varying stages of degeneration of the neutrophils.
** Ranges from nearly normal neutrophils, through pyknosis, karyorrhexis and karyolysis, finally to a homogenous, structureless, mixture of remnants.
*** Stains faintly bluish.
* There is a host inflammatory response directed against the sphere of pus as it is forming.
** Results in a capsule of fibrous tissue which has many blood vessels on its inner surface.
*** Allows the transport of the vast number of neutrophils into the necrotic centre.
*** Known as the 'pyogenic membrane'.
*** Can be viewed following abscess discharge as a crater that has a reddish, somewhat ragged lining.
*** The fibrous capsule around the pus is markedly thickened when the abscess is deep within an organ, such as the [[Liver - Anatomy & Physiology|liver]], and there is nowhere to discharge to.
===Caseation Necrosis===
* Caseation necrosis is a feature of granulomatous processes.
** E.g. tuberculosis in the ox, pig and sheep.
** Necrotic tissue is not derived from the organ in which it occurs.
*** Formed from [[Macrophages - WikiBlood|Macrophages]] sent into the tissue in large numbers to engulf the causative organism.
** The organism has defences against the enzymes of the [[Macrophages - WikiBlood|Macrophages]].
*** Is able to grow and multiply within these macrophages and eventually causes their death.
** In some granulomas, the macrophages will combine together and form giant cells.
** Fungi and parasites also cause granulomas.
====Gross====
* The necrotic tissue appears grossly like cheese.
** Colour varies from white-grey to yellowish.
*** Appears whitish in sheep.
*** There may be a yellowish tinge in cattle.
** Fluid content also varies.
*** Some cases have a dry, crumbling consistency
*** Others are more like cottage cheese.
* Caseation necrosis is really a mixture of [[Necrosis - Pathology#Coagulation Necrosis|coagulation]] and [[Necrosis - Pathology#Liquefactive Necrosis|liquefactive necrosis]].
** Is a feature of necrosis caused by some specific organisms.
====Histologically====
* There is complete loss of the tissue architecture.
* The necrotic material is purplish in colour
** Due to random intermixing of components that stain with haematoxylin and eosin.
*** I.e. bits of nuclear material interspersed with cytoplasmic fragments.
==Sequelae to Necrosis==
* Sequelae vary in relation to the causes of necrosis.
===Response to Local Injury===
* While a piece of dead tissue on the surface of the body (e.g. skin) can be shed, dead tissue in the depths of the body (e.g. [[Liver - Anatomy & Physiology|liver]]) cannot.
====In the Depths of the Body====
* Dead tissue in the center of the body can be
** Absorbed and replaced by fibrous tissue.
** Enclosed by fibrous tissue.
* As a general rule:
** Small areas of necrosis become absorbed and replaced by fibrous tissue.
*** Scars.
** Larger areas of necrosis become encapsulated by fibrous tissue.
*** Encapsulated portion is called a "sequestrum".
*** Cuts off any contact with living tissue
*** Allows further changes to occur to make the necrotic material more inert.
**** E.g. by [[Necrosis - Pathology#Calcification|calcification]]
====On an Epithelial Surface====
* There are two possible outcomes to necrosis occuring on an epithelial surface.
** Depends upon the depth of the necrosis.
* When the necrosis is confined to the middle and outer layers of the epithelium (an erosion), the underlying germinal layer divides and replaces the shed portion.
** Leaves no [[Healing and Repair - Pathology#Scarring|scar]].
** E.g. in [[Cavity & Gingiva - Pathology#Foot and Mouth disease|Foot and Mouth Disease]]
* When the necrosis extends below the basement membrane of the epithelium and the integrity of the epithelium is compromised (an ulceration), there is an inflammatory reaction.
** An attempt is made to repair the deficit by fibrous tissue.
*** Contraction of the fibrous tissue leaves a [[Healing and Repair - Pathology#Scarring|scar]].
** Caused e.g. by an applied corrosive substance or a burn.
===Fat Necrosis===
* Fat necrosis is confined to the fat depots of the body.
* Has a very distinctive gross appearance.
** The fat shows areas of focal opacity and is very hard.
*** Is normally semi-translucent and malleable.
* After the fat cells have died, the intracellular fat is broken down into fatty acids.
** These fatty acids combine with Ca<sup>++</sup>, Na<sup>+</sup> and K<sup>+</sup> ions to forms soaps.
* The soaps formed are foreign to the body and provoke an inflammatory response.
** These areas of fat necrosis remain indefinitely.
*** May show great scarring.
*** Quite often [[Necrosis - Pathology#Calcification|calcify]].
* Soaps do not dissolve out in routine preparation of sections.
* There are two principal methods of fat necrosis in the body:
** Enzymatic necrosis of fat.
** Traumatic necrosis of fat.
====Enzymatic Necrosis of Fat====
* Occurs when there is a release of pancreatic enzymes into the neighbouring mesenteric fat.
** Release is caused by a damaged pancreas.
*** E.g. due to an adjacent tumour.
====Traumatic Necrosis of Fat====
* Seen in the subcutaneous tissue following trauma to the area.
* Quite common in the brisket of recumbent animals due to the prolonged pressure on the area.
====Lipomatosis====
* Lipomatosis is another condition of fat that can involve necrosisis and calcification.
* Occurs for some unknown reason in Channel Island breeds of cattle.
* There are focal areas of increased fat in the mesentery.
** Often surround several loops of the gut.
*** If they become necrotic, they may strangle the enclosed gut with disastrous consequences for the animal.
===Gangrene===
* Gangrene is a post-necrotic change.
** In some cases is gangrene is the ultimate degradation of necrotic tissue.
* '''The tissue is already dead'''.
* There are two main types of gangrene.
*# '''Wet gangrene'''
*#* Life-threatening
*# '''Dry gangrene'''
*#* Non life-threatening
====Wet gangrene====
* Wet gangrene can either be due to:
** The agent which initially kills the tissue.
*** Gangrene is just further putrifaction.
*** '''Primary gangrene'''.
**** E.g. gangrenous mastitis of the udder of the cow caused by [[Staphylococcus spp.#Staphylococcus aureus|''Staphylococcus aureus'']].
** Invasion of dead tissue by organisms which putrefy it.
*** '''Secondary gangrene'''.
**** E.g. following [[Necrosis - Pathology#Loss of Blood Supply|ischaemic necrosis of the gut]], the putrefactive organisms that are normally present in the gut invade the dead tissue.
* A further cause of wet gangrene is when a ligature around an extremity causes ischaemic
necrosis of tissue distal to it and the necrotic tissue becomes invaded with putrefactive
bacteria.
* Wet gangrene is overwhelming disastrous for the animal unless treated quickly and effectively.
** The animal rapidly succumbs to toxaemia.
*** The organisms produce potent toxins, either themselves, or in their breakdown of the dead tissue.
=====Gross Appearance=====
* Tissue
** Is swollen and puffy
** Is cold to the touch
** Smells horrible
*** Due to the hydrogen sulphide produced in the putrefying tissue.
* The zone of inflammation between the dead putrefying tissue and living tissue is indistinct.
=====Gas Gangrene=====
* A variation of wet gangrene.
* Produced by [[Clostridium species|''Clostridia'']] organisms such as [[Clostridium species|''Clostridium chauvei'']] and [[Clostridium species|''C. septicum'']].
** Organisms also form gas.
* E.g. in Blackleg, and [[Clostridium species|''Clostridia'']] contamination of wounds.
====Dry Gangrene====
* Not life threatening.
* Is really mummification of an extremity.
** E.g. the tail, foot or ears of animals.
* There is occlusion of the blood supply to the extremity.
** The tissue becomes necrotic.
** Water is drawn out of the tissue due to air circulating around the extremity.
*** Dries and preserves the extremity.
**** Eventually sloughs off.
* Little if any bacterial growth in the tissue.
* E.g.:
** In small animals
*** Crushing of the tail.
** In large animals.
*** Commonly seen following a septicaemic condition when an embolus blocks the blood supply.
**** When seen in calves, the possibility of [[Intestines Fibrinous/Haemorrhagic Enteritis - Pathology#Salmonellosis|salmonellosis]] must be kept in mind.
*** Other causes are frostbite and [[Skin Environmental - Pathology#Ergot poisoning|ergot poisoning]].
==Calcification==
* In calcification, calcium salts are deposited within the necrotic tissue to make it more inert.
** Does NOT result from elevated blood calcium levels.
** Seen quite commonly in necrosis in cattle and sheep.
** Is a common feature in lesions which show [[Necrosis - Pathology#Caseation Necrosis|caseation necrosis]].
* Usually indicates a lesion of long standing.
===Gross Appearance===
* The deposits of calcium salts can be palpated.
* On cutting into the necrotic area, the calcified material may be:
** Felt as a gritty substance.
** Heard as a grating sound against the knife.
* The colour is usually chalk-white.
** There may be a yellowish-green tinge if the inciting cause is a parasite.
*** Due to attraction of a large number of [[Eosinophils - WikiBlood|eosinophils]].
===Histological Appearance===
* Calcium has a distinctive dark blue colour when stained with H&E.
** Some bacterial colonies stain a similar colour.
*** May be difficult to distiunguish calcium form these.
* Sections may show shattering of the calcium and adjacent tissue due to the effect of the microtome knife.
** Blunts the knife - there may be score marks throughout the rest of the section.
* Sections may be stained with silver nitrate to check for calcium by the von Kossa method.
** The calcium stains black.
==Apoptosis==
* '''Apoptosis is another method of cell death'''.
** Programmed death of scattered single cells in living tissues.
* Unlike necrosis, there is no reaction to the death of the cell.
* It is thought that some cells are programmed to die unless there is a change in circumstances that require them to continue living. This is a form of cell regulation.
** One such circumstance is the development of tumours.
*** Cellular regulation is absent.
* Cellular apoptosis is important in many processes:
** The deletion of extra cells produced in embryogenesis.
** Cyclical physiological changes in the genital tract of females.
** The death of lymphocytes
** Graft rejection
** Cellular death by the same injurious substances that cause necrosis in higher doses.
* The process of apoptosis:
** Cells lose their connections with their neighbours and shrink.
** The nucleus becomes pyknotic.
** The cytoplasm becomes eosinophilic.
** The cell breaks up into fragments that are engulfed by neighbouring cells or local macrophages.
*** Their remnants can be seen in the neighbouring cells’ cytoplasm.
{{toplink
|linkpage =General Pathology
|linktext =General Pathology
|maplink = General Pathology (Content Map)
|pagetype =Pathology
}}
<br>
==Introduction==
* '''Necrosis''' means the death of cells within the living body.
* Two things happen when necrosis occurs:
*# Further changes can take place in the tissue itself.
*# The surrounding unaffected living tissue can react against this necrotic tissue.
==Causes of Necrosis==
* There are three main causes of necrosis:
*# Loss of blood supply.
*#* Tissues depend upon their blood supply to remain alive.
*# Non-living agents such as chemicals or physical injuries.
*# Living agents such as [[Bacteria|bacteria]], [[Viruses|viruses]], [[Fungi|fungi]] or [[Parasites|parasites]].
===Loss of Blood Supply===
* Necrosis due to interuption of blood supply to a portion of tissue is known as '''ischaemic necrosis''', or [[Ischaemia and Infarction - Pathology#Infarction|'''infarction''']].
* The effects of [[Ischaemia and Infarction - Pathology#Ischaemia|ischaemia]] on a tissue vary according to:
** The tissue affected.
*** Some tissues are more susceptible than others.
** The type of cell in the tissue.
*** Generally, parenchymatous (functioning) cells are more susceptible than the stromal supporting cells.
** The metabolic activity of the tissue.
*** Very active organs are more susceptible.
** Whether there is a good or potential collateral blood supply.
* Tissue [[Ischaemia and Infarction - Pathology#Ischaemia|ischamia]] can be brought about in three ways:
** Compression of the blood vessel.
** Narrowing of the lumen.
** Blocking of the lumen .
====Compression of the Blood Vessel====
* A common cause of tissue ischaemia is [[Intestine Physical Disturbances - Pathology#Positional Changes/ Displacements|strangulation of the intestine]] by a twist upon itself.
** Compression of the mesenteric veins prevents outflow of blood
*** The affected portion becomes congested and swollen.
** The arterial supply cannot supply sufficient blood because of pressure in the swollen intestine and its vessels.
*** The affected area undergoes an ischaemic necrosis.
**** Sequelae include
***** Rupture and peritonitis
***** [[Necrosis - Pathology#Gangrene|Gangrene]] and toxaemia
****** Due to absorption of toxic products of the necrosis and intestinal bacteria.
* Another cause is a mass, such a lipoma, forming in the mesentery
** Becomes pedunculated (attached by a fine band of the mesentery).
*** Can encompass and strangulate a portion of intestine.
====Narrowing of the Lumen====
* E.g. thickening of the wall in arteriosclerosis.
====Blocking of the Lumen====
* Important causes are [[Thrombosis - Pathology#Introduction|thrombi]] and [[Thrombosis - Pathology#Embolism|emboli]].
* Renal vessels are commonly affected.
===Physical or Chemical Agents===
====Physical Agents====
* Include:
** Burns
** Cold
** Frostbite
** X-rays
** Pressure
** Pinching or crushing of the tissue.
* Necrosis my be:
** Direct
*** E.g. in the case of burns.
** Indirect
*** E.g. in crushing or pinching.
*** Vessels supplying the tissue are occluded, leading to necrosis of the tissue.
====Chemical Agents====
* May be directly caustic or corrosive in action.
* May exert their effects when absorbed and metabolised to a more toxic substance.
===Living agents===
* Living agents exert their effects though either
** Their toxic effects on cells, or
** Their colonisation of the cells.
==Appearance of Necrotic Lesions==
* There are three zones in a typical necrotic lesion.
*# There is a sphere of necrosis where the effect of the causal agent is maximal.
*# A little further away there is a zone where the tissue is damaged, but not yet dead.
*# Still farther away, the effect of the agent is insufficient to cause death or degeneration of cells.
*#* There is a zone where the body is reacting to the dead tissue.
===Gross and Histological Features of Necrotic Tissue===
* A change in colour is seen in necrotic tissue,
** Dead tissue tends to be paler than live tissue.
*** This is partly because there is no circulation.
* There is also a change in the consistency of the tissue.
*The appearance of the centre of the necrotic lesion varies according to:
*# The type of agent responsible
*# The tissue in which the agent is acting.
** This appearance may give a clue to the agent responsible.
==Types of Necrosis==
* The types of necrosis encountered are based on their gross description.
===Coagulation Necrosis===
* Coagulation necrosis is a feature of:
** Bacteria which produce toxins
** Infarction
** Some foci of viral replication.
=====Gross=====
* The necrotic lesion is firmer and dryer on the cut surface. The
* There is some resemblance to the nearby living tissue.
=====Histological=====
[[Image:coagulative_necrosis.jpg|right|thumb|100px|<small><center>Renal infarct - Coagulative Necrosis(Courtesy of S. Rhind)</center></small>]]
* The general architecture of the tissue is preserved.
* Certain changes related to loss of cellular detail can be recognised in an ordinary H&E section.
** Cells may appear larger and their outline may be lost
** Cytoplasm appears structureless and homogenous.
** There are '''nuclear changes'''
*** This is the most important feature.
* There are '''three types''' of '''nuclear change'''.
*# '''Pyknosis'''
*#* Greek for dense.
*#* The normal nuclear structure is replaced by a very dense, heavily staining, smaller, angular mass of chromatin.
*# '''Karyorrhexis'''
*#* This is from the Greek:
*#** karyon = nucleus
*#** rhexis = breaking up
*#* The nucleus appears as though it has exploded rather than condensed.
*#** Irregular-sized bits of dense nuclear material are found scattered throughout the centre of the cytoplasm.
*#** A kind of "reverse appearance" to pyknosis.
*# '''Karyolysis'''
*#* Karyolysis means dissolution of the nucleus.
*#* The nucleus is more faintly stained with haematoxylin.
*#** Only the ghost outline of the nucleus remains.
===Liquefactive Necrosis===
====Malacia====
* This is liquefactive necrosis in the brain.
* There is a lot of lipid in the brain.
** The intracellular enzymatic changes involved in necrosis make this softer and more fluid.
* Initially the affected area becomes swollen and gelatinous.
** Is sometimes bloodtinged due to disruption of the blood vessels.
**Later the area becomes fluid.
* The microscopic appearance does not resemble the nearby living tissue.
** The tissue is becoming a fluid.
====Pus Formation====
* Occurs when the organism causing the initial necrosis in the tissue is capable of attracting and killing large numbers of [[Neutrophils - WikiBlood|neutrophils]].
** I.e the '''pyogenic bacteria'''.
* [[Neutrophils - WikiBlood|Neutrophils]] release proteolytic enzymes when they die.
** These digest the dead tissue and also more incoming neutrophils.
*** The liquid formed is called '''pus'''.
* Pus is mainly composed of dead and dying neutrophils .
** Also contains the remnants of the necrotic tissue cells.
* Although in favourable cases the neutrophils may eventually kill the organisms, in most cases the organisms persist, producing more pus.
** Produces an expanding sphere of pus known as an [[Acute Inflammation - Pathology#Purulent|'''abscess''']].
*** If the abscess is near to the skin and pressure becomes sufficient after build up, it will burst.
**** Pus is discharged, hopefully along with the organisms responsible.
**** This is nature's way of ridding the body of an injurious agent.
=====Histological Appearance of an Abscess=====
* The necrotic area shows varying stages of degeneration of the neutrophils.
** Ranges from nearly normal neutrophils, through pyknosis, karyorrhexis and karyolysis, finally to a homogenous, structureless, mixture of remnants.
*** Stains faintly bluish.
* There is a host inflammatory response directed against the sphere of pus as it is forming.
** Results in a capsule of fibrous tissue which has many blood vessels on its inner surface.
*** Allows the transport of the vast number of neutrophils into the necrotic centre.
*** Known as the 'pyogenic membrane'.
*** Can be viewed following abscess discharge as a crater that has a reddish, somewhat ragged lining.
*** The fibrous capsule around the pus is markedly thickened when the abscess is deep within an organ, such as the [[Liver - Anatomy & Physiology|liver]], and there is nowhere to discharge to.
===Caseation Necrosis===
* Caseation necrosis is a feature of granulomatous processes.
** E.g. tuberculosis in the ox, pig and sheep.
** Necrotic tissue is not derived from the organ in which it occurs.
*** Formed from [[Macrophages - WikiBlood|Macrophages]] sent into the tissue in large numbers to engulf the causative organism.
** The organism has defences against the enzymes of the [[Macrophages - WikiBlood|Macrophages]].
*** Is able to grow and multiply within these macrophages and eventually causes their death.
** In some granulomas, the macrophages will combine together and form giant cells.
** Fungi and parasites also cause granulomas.
====Gross====
* The necrotic tissue appears grossly like cheese.
** Colour varies from white-grey to yellowish.
*** Appears whitish in sheep.
*** There may be a yellowish tinge in cattle.
** Fluid content also varies.
*** Some cases have a dry, crumbling consistency
*** Others are more like cottage cheese.
* Caseation necrosis is really a mixture of [[Necrosis - Pathology#Coagulation Necrosis|coagulation]] and [[Necrosis - Pathology#Liquefactive Necrosis|liquefactive necrosis]].
** Is a feature of necrosis caused by some specific organisms.
====Histologically====
* There is complete loss of the tissue architecture.
* The necrotic material is purplish in colour
** Due to random intermixing of components that stain with haematoxylin and eosin.
*** I.e. bits of nuclear material interspersed with cytoplasmic fragments.
==Sequelae to Necrosis==
* Sequelae vary in relation to the causes of necrosis.
===Response to Local Injury===
* While a piece of dead tissue on the surface of the body (e.g. skin) can be shed, dead tissue in the depths of the body (e.g. [[Liver - Anatomy & Physiology|liver]]) cannot.
====In the Depths of the Body====
* Dead tissue in the center of the body can be
** Absorbed and replaced by fibrous tissue.
** Enclosed by fibrous tissue.
* As a general rule:
** Small areas of necrosis become absorbed and replaced by fibrous tissue.
*** Scars.
** Larger areas of necrosis become encapsulated by fibrous tissue.
*** Encapsulated portion is called a "sequestrum".
*** Cuts off any contact with living tissue
*** Allows further changes to occur to make the necrotic material more inert.
**** E.g. by [[Necrosis - Pathology#Calcification|calcification]]
====On an Epithelial Surface====
* There are two possible outcomes to necrosis occuring on an epithelial surface.
** Depends upon the depth of the necrosis.
* When the necrosis is confined to the middle and outer layers of the epithelium (an erosion), the underlying germinal layer divides and replaces the shed portion.
** Leaves no [[Healing and Repair - Pathology#Scarring|scar]].
** E.g. in [[Cavity & Gingiva - Pathology#Foot and Mouth disease|Foot and Mouth Disease]]
* When the necrosis extends below the basement membrane of the epithelium and the integrity of the epithelium is compromised (an ulceration), there is an inflammatory reaction.
** An attempt is made to repair the deficit by fibrous tissue.
*** Contraction of the fibrous tissue leaves a [[Healing and Repair - Pathology#Scarring|scar]].
** Caused e.g. by an applied corrosive substance or a burn.
===Fat Necrosis===
* Fat necrosis is confined to the fat depots of the body.
* Has a very distinctive gross appearance.
** The fat shows areas of focal opacity and is very hard.
*** Is normally semi-translucent and malleable.
* After the fat cells have died, the intracellular fat is broken down into fatty acids.
** These fatty acids combine with Ca<sup>++</sup>, Na<sup>+</sup> and K<sup>+</sup> ions to forms soaps.
* The soaps formed are foreign to the body and provoke an inflammatory response.
** These areas of fat necrosis remain indefinitely.
*** May show great scarring.
*** Quite often [[Necrosis - Pathology#Calcification|calcify]].
* Soaps do not dissolve out in routine preparation of sections.
* There are two principal methods of fat necrosis in the body:
** Enzymatic necrosis of fat.
** Traumatic necrosis of fat.
====Enzymatic Necrosis of Fat====
* Occurs when there is a release of pancreatic enzymes into the neighbouring mesenteric fat.
** Release is caused by a damaged pancreas.
*** E.g. due to an adjacent tumour.
====Traumatic Necrosis of Fat====
* Seen in the subcutaneous tissue following trauma to the area.
* Quite common in the brisket of recumbent animals due to the prolonged pressure on the area.
====Lipomatosis====
* Lipomatosis is another condition of fat that can involve necrosisis and calcification.
* Occurs for some unknown reason in Channel Island breeds of cattle.
* There are focal areas of increased fat in the mesentery.
** Often surround several loops of the gut.
*** If they become necrotic, they may strangle the enclosed gut with disastrous consequences for the animal.
===Gangrene===
* Gangrene is a post-necrotic change.
** In some cases is gangrene is the ultimate degradation of necrotic tissue.
* '''The tissue is already dead'''.
* There are two main types of gangrene.
*# '''Wet gangrene'''
*#* Life-threatening
*# '''Dry gangrene'''
*#* Non life-threatening
====Wet gangrene====
* Wet gangrene can either be due to:
** The agent which initially kills the tissue.
*** Gangrene is just further putrifaction.
*** '''Primary gangrene'''.
**** E.g. gangrenous mastitis of the udder of the cow caused by [[Staphylococcus spp.#Staphylococcus aureus|''Staphylococcus aureus'']].
** Invasion of dead tissue by organisms which putrefy it.
*** '''Secondary gangrene'''.
**** E.g. following [[Necrosis - Pathology#Loss of Blood Supply|ischaemic necrosis of the gut]], the putrefactive organisms that are normally present in the gut invade the dead tissue.
* A further cause of wet gangrene is when a ligature around an extremity causes ischaemic
necrosis of tissue distal to it and the necrotic tissue becomes invaded with putrefactive
bacteria.
* Wet gangrene is overwhelming disastrous for the animal unless treated quickly and effectively.
** The animal rapidly succumbs to toxaemia.
*** The organisms produce potent toxins, either themselves, or in their breakdown of the dead tissue.
=====Gross Appearance=====
* Tissue
** Is swollen and puffy
** Is cold to the touch
** Smells horrible
*** Due to the hydrogen sulphide produced in the putrefying tissue.
* The zone of inflammation between the dead putrefying tissue and living tissue is indistinct.
=====Gas Gangrene=====
* A variation of wet gangrene.
* Produced by [[Clostridium species|''Clostridia'']] organisms such as [[Clostridium species|''Clostridium chauvei'']] and [[Clostridium species|''C. septicum'']].
** Organisms also form gas.
* E.g. in Blackleg, and [[Clostridium species|''Clostridia'']] contamination of wounds.
====Dry Gangrene====
* Not life threatening.
* Is really mummification of an extremity.
** E.g. the tail, foot or ears of animals.
* There is occlusion of the blood supply to the extremity.
** The tissue becomes necrotic.
** Water is drawn out of the tissue due to air circulating around the extremity.
*** Dries and preserves the extremity.
**** Eventually sloughs off.
* Little if any bacterial growth in the tissue.
* E.g.:
** In small animals
*** Crushing of the tail.
** In large animals.
*** Commonly seen following a septicaemic condition when an embolus blocks the blood supply.
**** When seen in calves, the possibility of [[Intestines Fibrinous/Haemorrhagic Enteritis - Pathology#Salmonellosis|salmonellosis]] must be kept in mind.
*** Other causes are frostbite and [[Skin Environmental - Pathology#Ergot poisoning|ergot poisoning]].
==Calcification==
* In calcification, calcium salts are deposited within the necrotic tissue to make it more inert.
** Does NOT result from elevated blood calcium levels.
** Seen quite commonly in necrosis in cattle and sheep.
** Is a common feature in lesions which show [[Necrosis - Pathology#Caseation Necrosis|caseation necrosis]].
* Usually indicates a lesion of long standing.
===Gross Appearance===
* The deposits of calcium salts can be palpated.
* On cutting into the necrotic area, the calcified material may be:
** Felt as a gritty substance.
** Heard as a grating sound against the knife.
* The colour is usually chalk-white.
** There may be a yellowish-green tinge if the inciting cause is a parasite.
*** Due to attraction of a large number of [[Eosinophils - WikiBlood|eosinophils]].
===Histological Appearance===
* Calcium has a distinctive dark blue colour when stained with H&E.
** Some bacterial colonies stain a similar colour.
*** May be difficult to distiunguish calcium form these.
* Sections may show shattering of the calcium and adjacent tissue due to the effect of the microtome knife.
** Blunts the knife - there may be score marks throughout the rest of the section.
* Sections may be stained with silver nitrate to check for calcium by the von Kossa method.
** The calcium stains black.
==Apoptosis==
* '''Apoptosis is another method of cell death'''.
** Programmed death of scattered single cells in living tissues.
* Unlike necrosis, there is no reaction to the death of the cell.
* It is thought that some cells are programmed to die unless there is a change in circumstances that require them to continue living. This is a form of cell regulation.
** One such circumstance is the development of tumours.
*** Cellular regulation is absent.
* Cellular apoptosis is important in many processes:
** The deletion of extra cells produced in embryogenesis.
** Cyclical physiological changes in the genital tract of females.
** The death of lymphocytes
** Graft rejection
** Cellular death by the same injurious substances that cause necrosis in higher doses.
* The process of apoptosis:
** Cells lose their connections with their neighbours and shrink.
** The nucleus becomes pyknotic.
** The cytoplasm becomes eosinophilic.
** The cell breaks up into fragments that are engulfed by neighbouring cells or local macrophages.
*** Their remnants can be seen in the neighbouring cells’ cytoplasm.