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| ==Necrosis== | | ==Necrosis== |
| + | Necrosis |
| + | The term necrosis means death of cells within the living body. |
| + | Two things happen when necrosis occurs: |
| + | a. further changes can take place in the tissue itself; and |
| + | b. the surrounding unaffected living tissue can react against this necrotic tissue. |
| + | Causes of Necrosis. |
| + | There are three main causes of necrosis: |
| + | 1. loss of blood supply - tissues depend upon their blood supply to remain alive, |
| + | 2. non-living agents such as chemicals or physical injuries, |
| + | 3. living agents such as bacteria, viruses, fungi or parasites. |
| + | 1. Loss of blood supply |
| + | .A diminished blood supply to a tissue is called ischaemia. This type of necrosis is called |
| + | ischaemic necrosis, also called infarction - defined as necrosis of a portion of tissue due to |
| + | an interruption (usually sudden) in the blood supply to that portion. The effects of |
| + | ischaemia on a tissue will vary according to: |
| + | a. the type of tissue affected - some tissues are more susceptible than others. |
| + | b. the type of cell in the tissue - the general rule is that parenchymatous cells, the |
| + | essential functioning cells, are more susceptible than the stromal supporting cells. |
| + | c. the metabolic activity of the tissue - very active organs i.e. those that work continuously |
| + | are more susceptible. |
| + | d. whether or not there is a good or potential collateral blood supply |
| + | 25 |
| + | There are three ways in which tissue ischaemia can be brought about |
| + | a. compression of the blood vessel |
| + | from without e.g. too tight a bandage |
| + | will cause tissue ischaemia. A |
| + | common cause of tissue ischaemia is |
| + | strangulation of the intestine by a |
| + | twist upon itself, or a mass such a |
| + | lipoma ( a relatively common growth |
| + | of mature fat tissue ) forms in the |
| + | mesentery, becomes pedunculated ( |
| + | attached by a fine band of the |
| + | mesentery) and can encompass a |
| + | portion of intestine. Initially, the |
| + | compression of the mesenteric veins |
| + | will prevent outflow of blood leading |
| + | to congestion and swelling of the |
| + | affected portion. When the arterial |
| + | supply becomes occluded or cannot |
| + | supply sufficient blood to the tissue |
| + | because of pressure in the swollen |
| + | intestine and its vessels, the affected area undergoes an ischaemic necrosis with disastrous |
| + | sequelae of rupture and peritonitis or gangrene and toxaemia due to absorption of toxic |
| + | products of the necrosis and intestinal bacteria. |
| + | b. a narrowing of the lumen e.g. thickening of the wall in arteriosclerosis. |
| + | c. blocking of the lumen of the vessel, important causes are thrombi and emboli. Renal |
| + | vessels are commonly affected. See the effects of emboli in Circulatory Disorders. |
| + | 2. The action of physical or chemical agents. |
| + | The physical agents include burns, cold, frostbite, X-rays, pressure, and actual pinching or |
| + | crushing of the tissue. The necrosis is direct in the case of burns and indirect in the case of |
| + | crushing or pinching which causes occlusion of the vessels supplying the tissue which will |
| + | undergo necrosis. Chemical agents may be directly caustic or corrosive in action or exert |
| + | their effects when absorbed and metabolised to a more toxic substance. |
| + | 3. Living agents - their effect is either through their toxic effects on cells or their |
| + | colonisation of the cells. |
| + | Appearance of necrotic lesions |
| + | In a typical necrotic lesion there are three zones. |
| + | 1. Where the effect of the causal agent is maximal, there is a sphere of necrosis. |
| + | 2. A little further away, the tissue will be damaged but not yet dead, and so there is a |
| + | zone of degeneration short of death. |
| + | 3. Still farther away, where the effect of the agent is insufficient to cause death or |
| + | degeneration of cells, we have a zone where the body is reacting to the dead tissue |
| + | 26 |
| + | Gross and histological features of necrotic tissue. |
| + | 1. Colour change in the tissue. In contrast to living tissue, dead tissue tends to be paler, |
| + | partly because there is no circulation in dead tissue |
| + | 2. Consistency (texture) of the tissue. The appearance of the centre of the necrotic lesion |
| + | will vary according to the |
| + | 1. type of agent responsible and |
| + | 2. the tissue in which it is acting. |
| + | This appearance may give a clue to the agent responsible, and the types of necrosis |
| + | encountered are based on their gross description |
| + | a. Coagulation necrosis |
| + | Gross: The necrotic lesion will be |
| + | firmer and dryer on the cut surface. The |
| + | gross appearance still resembles |
| + | somewhat the nearby living tissue. It is |
| + | a feature of bacteria which produce |
| + | toxins, infarction, and some foci of |
| + | viral replication. |
| + | Micro: the general architecture of the |
| + | tissue is preserved. Certain changes |
| + | present can be recognised in an ordinary |
| + | H&E section, and are related to loss of |
| + | cellular detail. |
| + | a. the cells may appear somewhat |
| + | larger and their outline may be lost |
| + | b. the cytoplasm appears structureless |
| + | and homogenous. |
| + | c. there are nuclear changes - the most important |
| + | 27 |
| + | There are three types of nuclear change. |
| + | i. Pyknosis - Greek for dense - is a |
| + | condition in which the normal nuclear |
| + | structure is replaced by a very dense, |
| + | heavily staining, somewhat smaller angular |
| + | mass of chromatin. |
| + | ii. Karyorrhexis - Greek karyon = |
| + | nucleus; rhexis = breaking up. This |
| + | appearance is rather the reverse of the |
| + | above. It appears as though the nucleus has |
| + | exploded rather than condensed in the |
| + | cytoplasm, and irregular-sized bits of dense |
| + | nuclear material are found scattered |
| + | throughout the centre of the cytoplasm. |
| + | iii. Karyolysis - this means dissolution of the nucleus. The nuclear staining with |
| + | haematoxylin becomes fainter and only the ghost outline of the nucleus remains. |
| + | Apoptosis - is a term used to denote the 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 - a form of cell regulation in a tissue - unless there is a change in |
| + | circumstances in a tissue that require them to continue living. One such circumstance is the |
| + | development of tumours in which cellular regulation is absent. Cellular apoptosis is thought |
| + | to be important in deleting extra cells produced in embryogenesis, in cyclical physiological |
| + | changes in the genital tract of females, in the death of lymphocytes, in graft rejection, and in |
| + | cellular death by the same injurious substances that cause necrosis in higher doses. |
| + | The cells undergoing |
| + | apoptosis lose their |
| + | connections with their |
| + | neighbours and shrink; the |
| + | nucleus becomes pyknotic; |
| + | and 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. |
| + | 28 |
| + | b. Liquefactive (Colliquative) |
| + | Necrosis. |
| + | Gross: In the brain where there is a lot of |
| + | lipid, the intracellular enzymatic changes |
| + | make it softer and more fluid in nature. This |
| + | is known as 'malacia'. Initially it becomes |
| + | swollen with a gelatinous, sometimes bloodtinged |
| + | appearance due to disruption of the |
| + | blood vessels but later becomes fluid. |
| + | Micro: the microscopic appearance will |
| + | not resemble the nearby living tissue as it |
| + | may have already lost any semblance of the |
| + | nearby living tissue because it is becoming |
| + | a fluid. |
| + | Another type of liquefactive necrosis, |
| + | quite important is pus formation which |
| + | occurs when the organism causing the initial |
| + | necrosis in the tissue, is capable of attracting |
| + | to the necrotic area large numbers of |
| + | neutrophils and also capable of killing them. |
| + | These are the so-called pyogenic bacteria. |
| + | When the neutrophils die they release |
| + | proteolytic enzymes which digest the dead |
| + | tissue and also more incoming neutrophils. |
| + | The liquid formed is called pus, and it is |
| + | composed mainly of the dead and dying |
| + | neutrophils together with the remnants of |
| + | the necrotic tissue cells. |
| + | 29 |
| + | In favourable cases, the neutrophils may |
| + | eventually kill the organisms, but in most cases |
| + | the organisms persist, all the time producing |
| + | more pus. This produces an expanding |
| + | sphere of pus that is called an abscess. The |
| + | pressure will build up and if near to the skin |
| + | will cause pressure on the overlying skin, and |
| + | when the pressure is sufficient or the surgeon |
| + | lances it, the abscess will burst discharging the |
| + | pus, and hopefully with it the organisms responsible. This is nature’s way of ridding the body |
| + | of an injurious agent. |
| + | Micro: In the case of an |
| + | abscess, the necrotic area will |
| + | show varying stages of |
| + | degeneration of the |
| + | neutrophils, ranging from |
| + | nearly normal neutrophils, to |
| + | pyknosis, karyorrhexis and |
| + | karyolysis, and finally to a |
| + | homogenous structureless |
| + | admixture of remnants staining |
| + | faintly bluish. |
| + | As this sphere of pus is |
| + | forming, there is a host |
| + | inflammatory response directed against it. This is composed of a capsule of fibrous tissue in |
| + | which there are many blood vessels on its inner surface, which transport the vast number of |
| + | neutrophils into the necrotic centre. This is called the 'pyogenic membrane'. In superficial |
| + | abscesses, when the abscess has discharged to the surface, this membrane can be viewed as a |
| + | crater that has a reddish somewhat ragged lining. Where the abscess is deep within an organ |
| + | such as the liver, there is nowhere to discharge to, and the fibrous capsule around the pus is |
| + | markedly thickened. . |
| + | c. Caseation necrosis. |
| + | The necrotic tissue appears grossly like |
| + | cheese. The colour varies from white to |
| + | grey to yellowish. In sheep it appears |
| + | whitish while in cattle there may be a |
| + | yellowish tinge. The fluid content also |
| + | varies giving a dry crumbling consistency |
| + | in some cases to being more like cottage |
| + | cheese in others. It is really a mixture of |
| + | coagulation and liquefactive necrosis, |
| + | and is a feature of necrosis caused by |
| + | some specific organisms. |
| + | 30 |
| + | Micro: On histological section, there is a |
| + | complete loss of the architecture, the |
| + | necrotic material being purplish in colour |
| + | due to random intermixing of the |
| + | components that stain with haematoxylin |
| + | and eosin i.e. bits of nuclear material |
| + | interspersed with cytoplasmic fragments. |
| + | This type of necrosis is a feature of |
| + | granulomatous (tumour-like |
| + | proliferation of chronic inflammatory |
| + | cells) processes such as tuberculosis in |
| + | some species, as in the ox, pig and sheep. |
| + | The necrotic tissue is not derived |
| + | principally from the organ in which it |
| + | occurs, but from a special type of host |
| + | inflammatory cell - the macrophage - |
| + | which is sent into the tissue in large |
| + | numbers to engulf the organism. The |
| + | organism has defences against the enzymes of the macrophages and is quite willing to |
| + | continue to grow and multiply within these macrophages eventually causing their death. In |
| + | some granulomas, the macrophages will combine together and form giant cells. |
| + | Fungi and parasites also cause granulomas. |
| + | Calcification. In the condition of calcification, calcium salts are deposited within the |
| + | necrotic tissue in an effort to make it more inert. It is seen quite commonly in necrosis in |
| + | cattle and sheep, and is a common feature in lesions which show caseation necrosis, and |
| + | usually indicates a lesion of long standing. Such calcified necrotic tissue can be appreciated |
| + | grossly. The deposits of calcium salts can be palpated and on cutting into the necrotic |
| + | portion, the calcified material may be both felt as a gritty substance and heard by a grating |
| + | sound against the knife. |
| + | The colour is usually chalk-white but may have a yellowish green tinge if the inciting cause |
| + | is a parasite. Parasites attract a large number of eosinophils that are responsible for this |
| + | colour. This type of calcium deposition in necrotic tissue is called dystrophic calcification. |
| + | It is an attempt to make the tissue more inert. It does not result from elevated levels of |
| + | calcium in the blood. |
| + | Micro: In sections stained by H&E, calcium has a |
| + | distinctive dark blue colour. You may also see some |
| + | shattering of the calcium and adjacent tissue due to the |
| + | effect of the microtome knife |
| + | passing through it. It blunts the knife and there may be |
| + | score marks throughout the rest of the section. Difficulty |
| + | sometimes arises in distinguishing calcium from |
| + | bacterial colonies that stain a similar colour. A |
| + | definitive special stain for calcium is to stain the |
| + | section with silver nitrate (the von Kossa method). |
| + | The calcium stains black. |
| + | 31 |
| + | Sequel to necrosis |
| + | These will vary in relation to the causes of necrosis, but by and large it is important to |
| + | distinguish between dead tissue on the surface of the body and dead tissue in the depths of |
| + | the body; a piece of dead skin as compared with a portion of dead liver. |
| + | Dead tissue on the surface can be shed and is said to slough, whereas dead tissue in the centre |
| + | of the liver cannot naturally be shed from the surface. Something else happens to it. It can |
| + | either be absorbed or replaced by fibrous tissue, or it can be enclosed by fibrous tissue. This |
| + | is part of the process of inflammation - the response of the body to local injury. It is a |
| + | general rule that small areas of necrosis become absorbed and replaced by fibrous tissue |
| + | (scars) while larger areas become encapsulated by fibrous tissue, the necrotic portion |
| + | remaining in the centre. This effectively cuts off any contact with living tissue, and allows |
| + | perhaps further changes to occur within the necrotic portion to make it more inert. The |
| + | encapsulated portion is called a sequestrum. It can be, as mentioned before, be calcified to |
| + | make it more inert. |
| + | When necrosis occurs on an epithelial surface, two things may happen depending upon the |
| + | depth of the necrosis. In a case like 'Foot and Mouth' where the necrosis is confined to the |
| + | middle and outer layers of the epithelium, the remaining underlying germinal layer divides |
| + | and replaces the shed portion. This type of necrosis confined to the epithelium is called an |
| + | erosion. It leaves no scar. |
| + | When the necrosis extends below the basement membrane of the epithelium as might be |
| + | caused by an applied corrosive substance or a burn, the body reacts to this interruption in the |
| + | integrity of the epithelium with an underlying inflammatory reaction attempting to repair the |
| + | deficit by fibrous tissue. This type of necrosis is called ulceration, and the resultant |
| + | contraction of the fibrous tissue leaves a scar. |
| + | Fat necrosis |
| + | This is confined to the fat depots of the body. |
| + | It has a very distinctive appearance grossly: instead |
| + | of the fat being semi- translucent and malleable, it |
| + | shows areas of focal opacity and is very hard in |
| + | consistency. This appearance is due to the |
| + | intracellular fat after the fat cells have died, being |
| + | broken down into fatty acids which combine with |
| + | Ca++, Na+ and K+ ions to forms soaps. These soaps |
| + | are substances foreign to the body and they provoke a |
| + | host inflammatory response. Unlike fat, they do not |
| + | dissolve out in routine preparation of sections, |
| + | These areas of fat necrosis remain indefinitely, may |
| + | show great scarring, and quite often calcify. It occurs |
| + | principally in two ways in the body. |
| + | 32 |
| + | a. Enzymatic necrosis of fat. This happens when there is a release of pancreatic enzymes |
| + | into the neighbouring mesenteric fat, the release being caused by a damaged pancreas e.g. |
| + | due to an adjacent tumour. |
| + | b. Traumatic necrosis of fat. This is seen in the |
| + | subcutaneous tissue following trauma to the area. |
| + | It is quite common in the brisket of recumbent |
| + | animals due to the prolonged pressure on the area. |
| + | It is worth mentioning here another condition of fat that can also undergo necrosis and |
| + | calcify. This is the so-called lipomatosis that occurs for some unknown reason in Channel |
| + | Island breeds of cattle. In this condition, there are focal areas of increased fat in the |
| + | mesentery. They often surround several loops of the gut, and if they become necrotic, they |
| + | may strangle the enclosed gut with disastrous consequences for the animal.' |
| + | Gangrene |
| + | Gangrene is a post-necrotic change, and in some cases is the ultimate degradation of necrotic |
| + | tissue. The tissue is already dead. There are two main types |
| + | a. Wet gangrene - life threatening |
| + | b. Dry gangrene - non life threatening |
| + | a. Wet gangrene can either be due to: |
| + | a. the agent which initially kills the tissue, further putrefying it, or |
| + | b. the gangrene may be due to dead tissue killed by some other means being invaded by |
| + | organisms which putrefy it. |
| + | In other words the former may be viewed as a primary gangrene, while the latter is |
| + | secondary. |
| + | An example of the former is gangrenous mastitis of the udder of the cow caused by |
| + | Staphylococcus aureus, the organism killing the tissue and then putrefying it. |
| + | An example of secondary gangrene is that which occurs when a portion of gut twists on its |
| + | mesentery or when a lipomatous mass attached to a strand of mesentery, loops around a piece |
| + | of intestine as depicted earlier with regard to tissue ischaemia. The blood supply to the gut is |
| + | cut off, and the affected portion becomes necrotic. Wet gangrene supervenes when the |
| + | putrefactive organisms that are normally present in the gut invade the dead tissue. |
| + | 33 |
| + | 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. |
| + | The gross appearance is of a swollen puffy tissue cold to the touch and with a horrible smell |
| + | owing to the hydrogen sulphide (the smell of rotting flesh) produced in the putrefying tissue. |
| + | In comparison to other dead tissue the zone of inflammation between the dead putrefying |
| + | tissue and living tissue is indistinct. This type of gangrene is overwhelming disastrous for the |
| + | animal unless treated quickly and effectively, as the organisms produce potent toxins either |
| + | themselves or in their breakdown of the dead tissue and the animal rapidly succumbs to |
| + | toxaemia. |
| + | A variation of wet gangrene is that produced by Clostridia organisms such as Clostridium |
| + | chauvei and C. septicum whereby they also form gas. This is called gas gangrene. The |
| + | conditions of Blackleg and Clostridia contamination of wounds produce this type of |
| + | gangrene. |
| + | Dry gangrene, on the other hand, is not life threatening. This is really mummification |
| + | (like an Egyptian mummy) of an extremity, such as the tail, foot or ears of animals. There is |
| + | an occlusion of the blood supply to the extremity. The tissue becomes necrotic. |
| + | Because of air circulating around the extremity, water is drawn out of the tissue, drying and |
| + | preserving it. There is little if any bacterial growth in the tissue and it eventually sloughs off. |
| + | In small animals crushing of the tail may cause this by cutting off the blood supply. |
| + | 34 |
| + | In large animals, it is seen commonly following a septicaemic condition in which bacteria |
| + | are growing and passing around in the circulation. An embolus blocks the blood supply. |
| + | When seen in calves, the possibility of Salmonellosis must be kept in mind. Other causes |
| + | are frostbite and ergot poisoning. |
| + | Finally, necrosis is irreversible. |
| ===Causes of Necrosis=== | | ===Causes of Necrosis=== |
| ===Gross and Histological Features of Necrotic Lesions=== | | ===Gross and Histological Features of Necrotic Lesions=== |