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→Necrosis
==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
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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
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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===