Necrosis

 Necrosis is the death of tissue in a

living body. It is a complete and
irreversible ceasing of tissue
function. Necrosis is often
preceded by necrobiosis.
 There are such periods in it:
 1. Paranecrosis, which presents change
similar to necrotic, but they are reversible
 2. Necrobiosis, which presents irreversible
dystrophic changes, characterized by
prevalence of catabolic reactions over
anabolic ones
 3. Cell death. It is hard to define the time of
its occurrence
 4. Autolysis or autodigestion, which
presents destruction of the dead substance
under the influence of hydrolytic enzymes of
the dead cells and macrophages
 Morphologically necrosis is the
same as autolysis.
 Apoptosis
 Apoptosis is a specific type of death of
cells, so-called “programmed death of
cells”. At the basis of this process lies
the cell division into parts with the
formation of “apoptose bodies” (cell
parts, surrounded by membrane), with
subsequent phagocytosis of these
bodies by macrophages.
 Apoptosis in viral hepatitis
 Necrobiotic and necrotic processes are
constantly taking place in the body as
the manifestation of its normal vital
functions.
 Processes of physiologic destruction
and regeneration are constant
processes in the body
 Necrosis appears more often and
earlier in the functionally active
parenchymal structures (functionally
stressed structures of the myocardium,
distal and proximan parts of the kidney,
brain, neurons, etc)
 Part of the cell, whole cell, group of
cells, part of the tissue, part of the
whole organ or even part of the
organism may be subjected to
necrosis. Sometimes necrosis may
be defined only microscopically, in
other occasions – microscopically
and macroscopically.
 Microscopically signs of necrosis may be
found in the nucleus and in cytoplasm. But
sometimes it is difficult to define the state of
the cell even microscopically, especially at
early stage. Microscopic determination of
kidney death may be done only in 6 hours
after stop of blood circulation. So,
morphologic changes do not appear at the
moment of death, they appear later. Even
by histochemical methods we may
determine a myocardial infarction only in a
few hours after death of cells.
 Microscopically, the most typical signs are:
 Shrivelling of the nucleus. When chromatic
condensation occurs, which leads to
karyopycnosis;
 then the nucleus disintegrates into beads
(karyorrhexis),
 and then it dissolves (karyolysis). There are
the successive stages of the process, that
shows the dynamics of hydrolase activation.
 Karyopiknosis and karyorrhexis
 The denaturation and coagulation of
proteins in the cytoplasm take place. This is
followed by colliquation, and the
ultrastructures are destroyed. The changes
may embrace a part of the cell (focal
coagulation necrosis), and this part is
rejected, or it may take place in the whole
cell (cytoplasm coagulation). Coagulation is
followed by plasmorrhexis, when cytoplasm
disintegrates into beads. Then develops the
final stage of plasmolysis.
 The changes in the interstitial
substance and fiber structures are
swelling and lysis. In the adipose tissue
there is disintegration of neutral fats
with formation of fatty acids and soaps.
 During disintegration of the cell and the
interstitial substance, tissue detritus is
formed. Demarcational (with strict
borders) inflammation develops around
necrotic focus.
 Macroscopically, necrotic zone is changed,
too. The consistency, color and smell
change. Sometimes dead tissue becomes
dry and dense (mummification), and
somethimes it is flaccid and dissoluted
(myomalacia). Often the dead tissue has
yellowish-white color.
 Sometimes in may have dark red color.
Necrotic region in the uterus, intestine are of
dirty brown, grayish green or even black
color. At other times necrotic region may be
colored by bile.
 Classification
 Depending on the cause of necrosis we
differentiate the following types:
 Traumatic
 Toxic
 Trophoneurotic
 Allergic
 Vascular
 Traumatic necrosis appears as the
result of physical of chemical
agent’s influence onto the tissue. It
may be radiation, high and low
temperature (burns and frostbites),
electric trauma, edges of a wound
 Toxic necrosis occurs after toxin
influence of any origin or highly
aggressive chemical substances
 Trophoneurotic necrosis occurs after
the disturbance of nerve trophicity
 Allergic necrosis occurs in sensitized
human organism and is the
manifestation of immediate type
hypersensitivity reaction. It is usually
fibrinoid necrosis type.
 Vascular necrosis, which is also called
infarction, occurs in insufficient blood
circulation as a result of a prolonged
spasm, thrombosis, embolism (which
can be angiogenic, ischemic necrosis).
 Depending on the mechanism of
pathogenic factor influence, we
discern:
 direct necrosis, caused by direct
influence (as in trauma, toxins), and
 indirect necrosis, which occurs through
vascular and nervous endocrine
system. It should be noticed that direct
necrosis is usually observed in
children.
 Clinical-morphologic forms of
necrosis are defined according to
the structural and functional
peculiarities of the organs and
tissues where necrosis takes place,
as well as the reasons that caused
it, and conditions of development.
 We single out these types of
necrosis:
 Coagulation
 Colliquation or liquefactive
 Gangrene
 Sequester
 Infarction (ischemic)
 Coagulation (dry)
necrosis
 This type is characterized by the dead
This type is characterized by the dead
area being dry, think, grayish-yellow:
the tissue is dehydrated. The
conditions for the dry necrosis are
present in tissues rich in proteins and
poor in liquid. For instance, waxy
necrosis of the muscles in typhus,
caseous necrosis in tuberculosis, etc.
 Coagulative necrosis, infarction of adrenal gland,
microscopically
 Coagulative necrosis, fatty necrosis of pancreas
 Coagulative necrosis, fatty necrosis of pancreas,
microscopically
 Centrolobular necrosis of liver
 Colliquative necrosis
 Colliquative (wet) necrosis is
characterized by dissolution of
dead tissues. For example, the
focus of gray encephalomalacia.
 Colliquative
necrosis –
abscess of the
lung,
macroscopically
 Infarction of the brain, macroscopically
 Infarction of the brain, microscopically, low
magnification
 Gangrene
 Gangrene is a type of tissue necrosis
assosiated with the environment and
changes into black color due to ferric
sulfate formation. There is dry and wet
gangrene. In dry gangrene the dead
tissues dry out in the air,
mummufication occurs.
 Dry gangrene of the foot
 Gangrene of the toe, microscopically
 In wet gangrene the dead tissue is
subjected to action of putrefactive
microorganisms, becomes
edematic, fetid. Wet gangrene
develops more often in the tissues
rich in liquid (like intestines).
 Wet gangrene of lower extremity
 Bedsore is a variety of gangrene –
it is necrosis of tissues, the surface
areas of which are under pressure
of the body in bed. They most often
occur in the sacrum region or near
the spinal processes of vertebrae.
It is the trophoneurotic necrosis
that appears in severely injured or
sick persons.
 Sequester is an area of dead tissue,
which is not subjected to autolysis, but
is rejected from the body and located
among the living tissues. More often
sequesters can be found in
osteomyelitis. The sequestral capsule
and cavity are formed around such a
sequester. This cavity is filled with pus.
Sometimes this sequester comes out of
the cavity through a fistula. Sequesters
may appear in the place of bedsore
and in places of tick bites.
 Infarction
 Infarction is a type of necrosis which
appears in the internal organs in the
conditions of acute blood circulation
dysfunction in a definite place.
Infarction is the most common type of
necrosis. Its type, size, color and
consistency may vary. Often it has
wedge-like shape, such infarctions
occur in spleen, kidneys, lungs.
 Some infarctions have irregular
form, they occur in the heart, brain,
intestines. Infarction may affect the
major part of the organ or even the
whole organ (subtotal or total
infarction), or it may be only noticed
with microscope (microinfarction).
 By appearance there are three
types of infarction:
 White (anemic)
 White with hemorrhagic crown
 Red infarction
 White infarction
 White (ischemic, anemic) infarction
is a region of yellowish white color,
clearly bordered from the
surrounding tissues, and is most
often met in spleen and kidneys.
 White infarction with
hemorrhagic crown
 White infarction with hemorrhagic
crown is a region of yellowish white
tissue, surrounded by hemorrhagic
zone. It is formed as a result of vessel
spasm on the periphery of the
infarction and is followed by its
dilatation and development of
hemorrhages. Such infarctions are
found in the kidneys and myocardium.
 Red infarction
 In the red (hemorrhagic) infarction
the necrotic region is saturated with
blood. It is dark red and well
bordered. As a rule, it is found in
the lungs, and rarely in the
intestines, spleen and kidneys.
 Myocardial infarction has the most
significant meaning in the clinic. It
is met in atherosclerosis and
hypertensive disease, ischemic
heart disease (IHD).
 Myocardial infarction, microscopically
 Cerebral infarction is more often an
ischemic or white infarction, which
leads to cerebromalacia (or
encephalomalacia), the focus of
gray cerebromalacia. In the
infarction is caused by significant
dysfunction, then the necrotic focus
in the brain is saturated with blood
and becomes red – focus of red
cerebromalacia.
 Cerebral infarction, similar to
myocardial infarction, more often
occurs on background of
atherosclerosis and hypertension.
 Infarction of the brain, macroscopically
 Infarction of the brain, macroscopically, high
magnification
 In the lungs occurs hemorrhagic
infarction in majority of cases. It is well
bordered and has conical shape. The
base of the cone is nearer to the
pleura. Pulmonary hemorrhagic
infarction usually occurs on
background of venous congestion.
Massive hemorrhagic pulmonary
infarction may be the cause of adrenal
jaundice. White, anemic, pulmonary
infarction is very rare. It is sometimes
caused by sclerosis and bronchial
artery lumen obliteration.
 Renal infarction usually is white
(anemic) with hemorrhagic crown.
The necrotic conical part occupies
either cortical matter or the entire
thickness of parenchyma.
 Renal infarction, macroscopically
 Renal infarction, microscopically
 In spleen there is usually white
infarction, often with reactive
fibrinous capsules and subsequent
formation of commissures with the
diaphragm, parietal layer of the
peritoneum, intestinal loups.
Ischemic infarctions of spleen are
associated with thrombosis and
embolism.
 Infarction of spleen, macroscopically
 In the intestines the infarctions are
hemorrhagic, quite often they are
subjected to gangrenous lysis,
which leads to perforation of
intestinal wall and development of
peritonitis.
 Infarction of small intestine, macroscopically
 Retinal ocular infarctions are very
rare, same as hepatic, muscular
and bone infarctions.
 The reasons for development of
infarction are spasms, thrombosis,
or embolism of the arteries, organ
functioning in conditions of blood
circulation insufficiency. The
insufficiency of anastomosis and
collateral plays a great role in
development of infarction.
 The outcome of infarction as any other
necrotic process depends on the
disease peculiarities and the size of
necrosis. Smaller infarctions undergo
autolysis with subsequent
regeneration. More often organization
and scar formation take place.
Petrification, cyst formation or purulent
lysis are possible.
 The significance of infarction depends
on its size, and the organ where it
takes place.
 Termination of necrosis
 As a rule, a reactive (demarcational)
inflammation takes place around the
necrotic region; the border zone is
called demarcational zone. If the dead
tissue is replaced by the connective
tissue, this process is called
encapsulation. Sometimes calcium
salts may be found in the necrotic zone
(petrification).
 With time, bone may be formed in
the region of petrification
(ossification). Sometimes a cyst if
formed in the region of the
resorbed necrosis. The purulent
lysis of tissues is the most
unfavorable termination of
necrosis.
 The importance of necrosis is
defined by its nature, that is “local
death”. Necrosis of vitally important
organs often leads to death. Often
necrosis leads to decrease of
organ function, to intoxication.
Purulent lysis may be the cause of
purulent inflammation of serous
membranes and sepsis.
 Necrobiotic processes are normal
processes in biology.
Integumentary epithelium of the
skin, epithelium of digestive,
respiratory and urogenital tracts
constantly dissolutes and
regenerates.
 Death
 Death as biological notion is
manifestation of irreversible changes in
vital activity of the organism. When
death occurs, the organism becomes a
corpse.
 Depending on the reason leading to
death, there are discerned
physiological (or natural) death, death
by violence and death from disease.
 Physiological (or natural) death
usually takes place in the elderly as
a result of natural (physiologic)
aging. The term of human life has
not yet been defeined, however it
may not be less than 150 years.
Gerontology dealds with the
problems of aging, and geriatry
deals with the diseases of the
elderly.
 Death by violence takes place as a
result of somebody’s abuse over a
person. It may be a murder,
suicede, death from trauma,
accidents. Forensic medicine
studies death by violence.
 Death from disease occurs as result of
incompatibility of life with the changes
in the body that are caused by
pathological processes. Usually death
from disease progresses slowly and
may be prognosed with high level of
probability. If death occurs
unexpectedly, it is termed
“spontaneous death”. If death occurs in
a seemingly healthy person, it is called
“sudden death”.
 Death is not a momentary process.
It is stretched in time. There is
clinical and biological death.
 Clinical death
 Clinical death is a reversible process.
At its base lies state of hypoxia in
connection with blood circulation arrest.
It is preceded by agony, lasting from
minutes to hours. Agony is referred to
terminal conditions. Reanimatology
deals with those issues.
 Biological death
 Biological death presents irreversible
changes in the organism and beginning
of autolytic processes in it. However,
death of cells and tissues does not take
place at the same time. The central
nervous system (CNS) dies first (5
minutes). In other organs and systems
this process is prolonged for hours and
sometimes days.
 When clinical death occurs, there are
several symptoms or signs that may be
observed:
 Brunatis symptom is the agony stage sign in
severe diseases. It is opacification of the
cornea.
 Davis symptom is a possible death sign
(non-pulsating empty arteries on palpation,
with pale or yellowing spots over them)
 Hering’s symptom is a death sign, presents
a light humming noise, that may be heard
over the lower end of the breastbone, right
after ceasing of heart beat.
 Larchais symptom - when white membranes
of the eyes not covered by eyelids become
dull and pale gray due to drying in one hour
after death.
 Levasser’s symptom - when a scratch does
not bleed, there is no hemorrhage
 Monteverde’s symptom – when
subcutaneus injection of ammonia does not
evoke any reaction
 Beloglazov-Rino’s symptom – pressure onto
the eye-ball of a corpse leads to constant
deformation of pupil shape (which is
temporal in living organism)
 Cako symptom – so-called “reaction of
sirviving tissues”. On percussion some
definite points of muscles and tendons can
contract and move at corresponding joints
within 2 hours after onset of clinical death.
 All of those symptoms are not very reliable.

 There are pathoanatomical signs of death

and post-mortem changes. They are:
 Cooling down of corpse (algor mortis)
 Rigor mortis (rigidity of corpse)
 Drying up (or shriveling) of corpse
 Redistribution of blood
 Postmortem lividity
 Postmortem decomposition
 Cooling down or algor mortis develops in
connection with ceasing of heat production
in the organism. If before death the body
temperature was very high or in agony
period the patient had crapms or seizures,
the cooling down will take place slowly.
 In some cases (tetanus-like death)
temperature may even rise in a hew hours
immediately after death.
 Rigor mortis is muscular stiffening. It is caused
by disappearance of adenosine triphosphate
and accumulation of lactic acid in muscles after
death of the body. Rigor mortis usually
develops in 2-5 hours after death, and by the
end of 24 hours it extends to all muscles. It is
preserved for 2-3 days and then disappears in
the same consequence. If rigor mortis was
broken on purpose it does not restore. Rigor
mortis is well manifested in corpses with well-
trained muscles and in cases when death
occurs with spasmodic seizures.
 Drying up or shrivelling of the corpse occurs
as result of fluid evaporation from body
surface. It may occur in some skin areas, or
the whole body may be drying up
(mummification).
 Redistribution of blood is manifested when
all the veins are full-blooded and arteries
are empty. Blood coagulation takes place in
larger vessels.
 Postmortem lividity appears as result of
blood flowing down into lower parts of the
body as it lies. In 3-6 hours dark violet
livedos (spots) turn pale on pressure
(postmortem hypostasis). Later in hemolysis
the region of hypostasis is infiltrated with
plasma colored with hemoglobin. These
spots have pinkish red color and do not
disappear on pressure (postmortem
imbibition).
 Postmortem putrefaction is connected with
autolysis processes. They are followed by
putrefactive processes. Gases are formed
(postmortem emphysema). It is very difficult
to slow the process of cadaveric
putrefaction. Freezing is the only reliable
method.