Alteration
Degenerations
Nekrosis
Lecture on pathological anatomy for
the 3-rd year students
T.Filonenko
Alteration. Cell injury.
Alteration is the pathological changes of cellular structure,
extracellular matrix, tissue and organs which are
accompanied by violation of their vital functions.
The cellular morphologic changes induced by various
stimuli can be divided into:
1. Patterns of acute cell injury — reversible and irreversible
cell injury leading to necrosis or apoptosis
2. Subcellular alterations that occur largely as a response to
more chronic or persistent injurious stimuli
3. Intracellular accumulations of a number of substances —
lipids, carbohydrates, proteins—as a result of
derangements in cell metabolism or excessive storage.
Reasons of development of
alteration
1. hypoxia
2. chemical agents and drugs
3. physical agents
4. microbiological agents (bacteria, viruses,
5.
6.
7.
8.
fungies)
immune mechanisms
genetic defects (apoptosis)
nutritional imbalances
aging
Classification of degenerations
1. Сlassification in depending on localization of metabolism:

parenchymal

stromally - vascular

mixed
2. Classification in depending on deposition of protein, lipids,
carbohydrate , mineral (on predominance of the broken
exchange):

Proteinous (Dysproteinoses)

Fatty (lipidoses)

Carbohydrate

Mineral

Pigmental
3. Classification in depending on prevalence of process:

Local

System
4. Classification in depending on an origin:

Acquired

Hereditary
Categories of intracellular
accumulations
1. a normal cellular constituent accumulated
in excess, such as water, lipid, protein,
and carbohydrates;
2. an abnormal substance, either exogenous,
such as a mineral, or a product of
abnormal metabolism;
3. a pigment or an infectious product.
Parenchymal dysproteinoses,
mechanisms.
Cell
Denaturation and
coagulation of
cytoplasmic proteins
Hydratation and
colliquation of cell’s
cytoplasm
Hyaline-drop dystrophy
Hydropic dystrophy
Focal coagulative
necrosis of cell
Focal colliquative
necrosis of cell
(balloon dystrophy)
Total colliquative
necrosis of cell
Total coagulativeNecrosis
of cell
The most frequent localization of
intracellular accumulations of
proteins, lipids and
carbohydrates is
myocardium (cardiomyocytes),
liver (hepatocytes),
kidneys (nephrocytes).
Types of intracellular
parenhymatous
degenerations
Granular
Hyaline-drop
Hydropic (vacuolar, balloon)
Keratoid (horney)
Here are Mallory bodies
Parenhymatous fatty degenerations
This liver is enlarged and has
a pale yellow appearance. It is
greasy to touch. It is called
“Goose liver”.
Microscopically: there
are numerous lipid
vacuoles in the
cytoplasm of
hepatocytes.
Extracellular proteinous
degenerations
1. Mukoid swelling
2. Fibrinoid changes
3. Hyalynosis
4. Amyloydosis
Mucoid swelling
It is disorganization and swelling of
perivascular extracellular matrix
(disorganization of connective
tissue) due to increased vascular
permeability, plasmorrhagia and
deposition of glucosaminoglycans
(GAG).
Microscopically: there is the phenomenon of metachromasia.
That is basophylic color of basic substances. Collagen fibers
save the structure, but swell and undergo to fibrillar
destructure.
Gross appearance: tissue or organ is saved.
Process is convertible.
Fibrinoid changes
It is deep and irreversible disorganization of
connective tissue, in basis of which destruction of
basic substances and fibers. It is accompanied
by the sharp increase of permeability of vessels
and formation of fibrinoid
masses.
Microscopically: the bands
of collagen fibers are
homogenous, impregnated
with plasma proteins.
Outcomes: fibrinoid
necrosis, hyalinosis,
sclerosis.
Hyaline change
It is an alteration within cells or in the extracellular
space, which gives a homogenous, glassy, pink
appearance in routine histologic sections
stained with H&E.
Hyalinosis is classified according
to its localization:
Vascular hyalinosis (arteries are
thickened with sharply narrowed
or obliterated lumen)
Hyalinosis of connective tissue is
usually localized; it develops in
scars, adhesions, in the areas of
chronic inflammation (e.g. “glazed
spleen”).
The outcome of hyalinosis is
irreversible.
Functional significance of hyalinosis
is different:
• Vascular hyalinosis may lead to
atrophy or sclerosis, infarction of
organs.
• Local hyalinosis in the cardiac
valves results in heart defects.
Amyloidosis
Amyloidosis is the term used for a group of diseases
characterized by extracellular deposition of febrillar
proteinaceous substance called amyloid.
Nature and etiology
Amyloid is composed of 2 main types of complex proteins:
Fibril proteins comprising about 90% of amyloid.
P-component comprising about 10% of amyloid.
Of the 15 biochemically distinct forms of amyloid
proteins that have been identified, two are the most
common:
One, called AL (amyloid light chain) is derived from
plasma cells (immunocytes) and contains immunoglobulin
light chains.
The other, designated AA (amyloid-associated), is a
unique nonimmunoglobulin protein synthesized by the
liver.
Classification of amyloidosis
A. Systemic Amyloidosis
1. Primary amyloidosis (idiopathic) is the defect
of primary mesodermal tissue
2. Secondary amyloidosis (acquired, reactive) is
complication of chronic diseases (chronic
infections, malignant tumors)
3. Familial amyloidosis (inherited, genetic) is
predisposition of certain ethnic groups (periodic
illness).
B. Localized Amyloidosis
1. Senile amyloidosis
2. Endocrine amyloidosis
Diagnosis of amyloidosis
Histologic examination of biopsy material
is the commonest and confirmatory
method for diagnosis in a suspected case
of amyloidosis.
If renal manifestations are present, kidney
is the preferred site for biopsy.
Other sites such as rectum, gingiva, and
more recently abdominal fat, are biopsied
and are followed by Congo red staining for
confirmation.
Pathology
Systemic amyloidosis (AA) related to chronic inflammation
tends to involve parenchymatous organs, such as kidneys,
spleen, liver, and adrenals.
While amyloidosis (AL) related to myeloma tends to affect
mesodermal or other tissues, such as heart, gastrointestinal
tract, peripheral nerves, skin, and tongue.
Grossly:
Organs extensively infiltrated by amyloid are usually enlarged
and have a pale, waxy ("lardaceous") or varnished appearance
and firm consistency.
The iodine test for amyloid is done by applying iodine solution
to the washed cut surface of the organ: amyloid typically stains
mahogany-brown, and this color reaction changes to blue ( a
"starch-like" reaction) after the application of dilute sulfuric acid
Primary amyloidosis of
kidneys.
Grossly, amyloid kidneys
are usually enlarged,
pale, and smooth
surfaced and have a firm
consistency. On cortical
transaction, the glomeruli
(visible as pink dots in the
normal kidney) may be
seen as enlarged, waxy,
gray dots.
Microscopically: the amorphous
pink deposition of amyloid may
be found in and around
arteries, in interstitium, or in
glomeruli. A Congo red stain
will demonstrate the red
material to be amyloid.
H&E
Congo red
Amyloidosis of
myocardium
This section of
myocardium
demonstrates
amorphous deposits of
pale pink (H&E ) or red
(Congo red) material
between myocardial
fibers. Amyloidosis is a
cause for "infiltrative" or
"restrictive"
cardiomyopathy.
Amyloidosis of the spleen
Amyloidosis
of the spleen has
two different anatomical
patterns. Most commonly, the
amyloid deposits is limited to
the splenic follicles, resulting in
the gross appearance of a
moderately enlarged spleen
dotted with gray nodules (so
called "sago" spleen).
Alternatively, the amyloid
deposits may spare the follicles
and mainly infiltrate the red
pulp sinuses, producing a
large, firm spleen mottled with
waxy discolorations
("lardaceous" spleen).
Amyloidosis of adrenal gland
Amyloid deposits
surround,
compress, and
replace some
cortical cells and
infiltrate the wall
of a small blood
vessel. Congo red.
Amyloidosis of the
tongue
Amyloid infiltrates the
capillary walls and
narrows the lumens
of some of them. H&E.
Amyloidosis of the liver
The hepatic parenchyma
is infiltrated and
replaced by nodular
accumulations of
amyloid (pink). H&E.
Clinical manifestations of amyloidosis
Stromal vascular fatty degenerations
• Stromal fatty infiltration is the deposition of mature adipose cells in the
stromal connective tissue.
• The condition occurs most often in patients with obesity.
Classifications of Obesity
1. According to the etiology : Primary (idiopathic) and
Secondary.
2. There are several types of secondary obesity: Alimentary,
Cerebral, Endocrine, Hereditary in Gierke’s disease.
3. According to the patient's appearance: symmetrical,
upper, medial, and lower.
4. According to morphological peculiarities of adipose
tissue:
• In hypertrophic type adipose tissue enlarges due to
increased volume of fatty cells
• In hyperplastic due to increase in their number.
PATHOLOGY OF PIGMENTS
Pigments are colored substances, some of which are
normal constituents of cells where as others are abnormal
and collect in cells only under special circumstances.
Pigments are generally classified into two broad categories:
1. Endogenous pigments, which are normal constituents of
cells and tissues;
2. Exogenous pigments introduced into the body from
environment.
1.


2.
3.
Classification of endogenous pigments
Hemoglobinogenic pigments:
Physiologic pigments: Ferritin, Hemosiderin, Bilirubin
Pathologic pigments: Hematoidin, Hematin, Porfirin
Proteinogenic (melanin).
Lipidogenic (lipofuscin).
Hemosiderosis
Local hemosiderosis is
characterized by local
breakdown of red cells in
tissues, e.g. in internal
hemorrhage.
Mechanism of local
hemosiderosis is
extravascular hemolysis.
It occurs regularly around
areas of bruising and
hemorrhage.
In the lungs hemosiderin-laden
macrophages (siderophages)
are appropriately referred to as
“heart failure cells”.
Visceral siderosis (systemic hemosiderosis).
A Prussian blue reaction is seen
in this iron stain of the liver to
demonstrate large amounts of
hemosiderin that are present in
hepatocytes and Kupffer cells.
Mechanism of systemic
hemosiderosis is intravascular
hemolysis.
It is seen in the liver, spleen
and sometimes in kidneys in
cases of hemolytic anemia, in
patients requiring repeated
blood transfusion, in patients
with chronic ineffective
erythropoiesis. The pigment
imparts a deep brown color to
tissues and organs when it is
present in high
concentrations.
Pathology of bilirubin’s metabolism.
Jaundice.
Types of jaundice:
1. Prehepatic jaundice (Hemolytic jaundice) is
characterized by lysis of the red blood cells in a variety of
conditions.
2. Intrahepatic jaundice (Hepatocellular jaundice) - results
from failure both of hepatocytes to conjugate bilirubin and
of bilirubin to pass through the liver into the intestine. Both
of conjugated bilirubin and unconjugated bilirubin increase
its amount in blood. The liver is light yellowish-green color
of saffron (“saffron liver”).
3. Posthepatic jaundice (Obstructive jaundice) - results
from an obstruction of the passage of conjugated bilirubin
from hepatocytes to the intestine. Conjugated bilirubin is
water-soluble and is excreted in the urine. The liver is dark
green.
In the liver, bile pigments may appear:
• As bile pigment droplets in the hepatocytes.
• As bile impregnations in necrotic areas.
• As bile casts (bile capillaries, cholangioles, or bile
canaliculi).
• In Kupffer’s cells.
The yellow-green globular
material seen in small bile
ductules in the liver here is
bilirubin pigment.
Calcium metabolism disturbances
This is dystrophic calcification in
the wall of the stomach. At the far
left is an artery with calcification
in its wall. There are also irregular
bluish-purple deposits of calcium
in the submucosa. Calcium is
more likely to be deposited in
tissues that are damaged.
Here is so-called
"metastatic calcification" in
the lung of a patient with a
very high serum calcium
level (hypercalcemia).
Cells Death
It is the premature death and destruction of
cell in the living organism under action of
factors of critical damage
Classification of Cells Death, based on the
mechanism of development:
necrosis
pathogenic inducted apoptosis
immunological elimination of cells.
NECROSIS
If the acute or chronic injury to which
a cell must react is too great, the
resulting changes in structure and
function lead to the death of cells.
Death of the cells and tissues in a
living organism is called Necrosis.
According to the cause of
necrosis there are the following
types of necrosis:
traumatic necrosis;
toxic necrosis;
trophoneurotic necrosis;
allergic necrosis;
vascular or ischemic necrosis.
Main types of necrosis
Two essential changes bring about irreversible cell
injury in necrosis - cell digestion by denaturation of
proteins and lytic enzymes.
coagulative necrosis develops (during denaturation of
proteins ).
liquefactive necrosis is a progressive catalysis of cell
structures (during enzymic digestion). Liquefactive
necrosis is typical of organs in which the tissues have a
lot of lipid (such as brain) or when there is an abscess
with lots of acute inflammatory cells whose release of
proteolytic
Both of these processes require hours to develop
Clinic-morphological forms of
necrosis of organs:
1) Gangrene – total necrosis of the organ, reported with the
external environment:
dry – at the thrombosis of arteries, an organ acquires the black coloring
moist (wet) – at the thrombosis of arteries and veins + influencing of putrid
bacteria.
gas gangrene
bedsore is a type of gangrene, death of the tissue under the influence of
pressure (sacral area, buttocks, great trochanter). It is trophoneurotic
necrosis of the bed- patients
noma – widespread necrosis of soft tissue of person.
2) Sequester – fragment of dead tissue, which can’t be autolysed,
replaced by connective tissue and which is localized among
alive tissue
3) Infarction – vascular or ischemic necrosis;
4) Fat necrosis
5) Caseous necrosis
6) Fibrinoid necrosis.
Infarction
This is an example of coagulative
necrosis. This is the typical pattern
with ischemia and infarction (loss of
blood supply and resultant tissue
anoxia). Here, there is a wedgeshaped pale area of coagulative
necrosis (infarction) in the renal
cortex of the kidney.
The contrast between normal adrenal
cortex and the small pale infarct is
good. The area just under the capsule
is spared because of blood supply
from capsular arterial branches. This
picture illustrates the shape and
appearance of an ischemic (pale)
infarct well.
Liquefactive necrosis
At high magnification, liquefactive
necrosis of the brain demonstrates
many macrophages at the right which
are cleaning up the necrotic cellular
debris.
Grossly, the cerebral infarction at
the upper left here demonstrates
liquefactive necrosis. Eventually, the
removal of the dead tissue leaves
behind a cavity
Gangrene
This is gangrene. In this case, the
toes were involved in a frostbite
injury. This is an example of "dry"
gangrene in which there is mainly
coagulative necrosis from the
anoxic injury.
This is gangrene of the lower
extremity. In this case the term
"wet" gangrene is more applicable
because of the liquefactive
component from superimposed
infection in addition to the
coagulative necrosis from loss of
blood supply. This patient had
diabetes mellitus.
Fat necrosis
This is fat necrosis of the pancreas.
Cellular injury to the pancreatic acini
leads to release of powerful enzymes
which damage fat by the production of
soaps, and these appear grossly as
the soft, chalky white areas seen here
on the cut surfaces.
Microscopically, fat necrosis is
seen here. Though the cellular
outlines vaguely remain, the fat
cells have lost their peripheral
nuclei and their cytoplasm has
become a pink amorphous mass
of necrotic material.
Caseous necrosis
This is more extensive caseous
necrosis, with confluent cheesy tan
granulomas in the upper portion of
this lung in a patient with tuberculosis.
The tissue destruction is so extensive
that there are areas of cavitation
(cystic spaces) being formed as the
necrotic (mainly liquefied) debris
drains out via the bronchi.
Microscopically, caseous necrosis is
characterized by acellular pink areas
of necrosis, as seen here at the upper
right, surrounded by a granulomatous
inflammatory process.
Fibrinoid necrosis
Sometimes the small arteries and arterioles can be
damaged so severely in malignant hypertension that they
demonstrate necrosis with a pink fibrin-like quality that gives
this process its name - fibrinoid necrosis.
Phase of necrosis
Many nuclei have become
pyknotic (shrunken and dark). It
process is called
karyopicnosis.
After that karyorrhexis
(fragmentation) develops.
Nucleus is decomposed into
small granules.
Also may be develops
karyolysis, when the nucleus
dissolves.
The cytoplasm and cell borders
are not recognizable.
The outcomes of necrosis
Regeneration of tissues – replacement of the dead tissue with a
new one;
Incapsulation – formation of the connective tissue capsula around
necrotic area;
Organization – replacement of the dead tissue with connective
tissue;
Petrification – replacement of the dead tissue with calcium salts;
Incrustation – replacement of the dead tissue with any other salts
exept calcium;
Ossification – the formation of the bone tissue in the necrotic area;
Hyaline change – the appearance of the hyaline-like substance in
the necrotic area;
Sequestration – formation of sequester;
Mutilation – spontaneous tearing away of the dead tissue;
Cystic formation.
Suppuration fusion of necrotic tissues