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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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| − | 25
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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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| − | 26
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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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| − | 27
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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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| − | 28
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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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| − | 29
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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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| − | 30
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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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| − | 31
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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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| − | 32
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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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| − | 33
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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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| − | 34
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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====
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| | | | |
| | ==Post Mortem Change== | | ==Post Mortem Change== |