Alteration Degenerations Nekrosis Lecture on pathological
anatomy for the 3-rd year students T.Filonenko
Slide 2
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,
proteinsas a result of derangements in cell metabolism or excessive
storage.
Slide 3
Reasons of development of alteration 1. hypoxia 2. chemical
agents and drugs 3. physical agents 4. microbiological agents
(bacteria, viruses, fungies) 5. immune mechanisms 6. genetic
defects (apoptosis) 7. nutritional imbalances 8. aging
Slide 4
Classification of degenerations 1. lassification 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
Slide 5
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.
Slide 6
Parenchymal dysproteinoses, mechanisms. Cell Denaturation and
coagulation of cytoplasmic proteins Hyaline-drop dystrophy Focal
coagulative necrosis of cell Total coagulativeNecrosis of cell
Hydratation and colliquation of cells cytoplasm Hydropic dystrophy
Focal colliquative necrosis of cell (balloon dystrophy) Total
colliquative necrosis of cell
Slide 7
The most frequent localization of intracellular accumulations
of proteins, lipids and carbohydrates is myocardium
(cardiomyocytes), liver (hepatocytes), kidneys (nephrocytes).
Slide 8
Types of intracellular parenhymatous degenerations
GranularHyaline-drop Hydropic (vacuolar, balloon) Keratoid (horney)
Here are Mallory bodies
Slide 9
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.
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.
Slide 12
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.
Slide 13
Hyaline change H&E. 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).
Slide 14
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.
Slide 15
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.
Slide 16
Classification of amyloidosis A. Systemic 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 1. Senile
amyloidosis 2. Endocrine amyloidosis
Slide 17
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. 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.
Slide 18
Pathology Systemic amyloidosis (AA) related to chronic
inflammation tends to involve parenchymatous organs, such
askidneys, 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
Slide 19
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.
Slide 20
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.
Slide 21
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. H&E Congo red Amyloidosis of
myocardium
Slide 22
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).
Slide 23
Amyloidosis of adrenal gland Amyloid deposits surround,
compress, and replace some cortical cells and infiltrate the wall
of a small blood vessel. Congo red.
Slide 24
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.
Slide 25
Clinical manifestations of amyloidosis
Slide 26
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 Gierkes
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.
Slide 27
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.
Classification of endogenous pigments 1. Hemoglobinogenic pigments:
Physiologic pigments: Ferritin, Hemosiderin, Bilirubin Pathologic
pigments: Hematoidin, Hematin, Porfirin 2. Proteinogenic (melanin).
3. Lipidogenic (lipofuscin).
Slide 28
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.
Slide 29
Visceral siderosis (systemic hemosiderosis). 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. 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.
Slide 30
Pathology of bilirubins 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.
Slide 31
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 Kupffers cells. The yellow-green globular material
seen in small bile ductules in the liver here is bilirubin
pigment.
Slide 32
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).
Calcium metabolism disturbances
Slide 33
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.
Slide 34
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. Death of the cells and tissues
in a living organism is called Necrosis.
Slide 35
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.
Slide 36
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 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 Main
types of necrosis
Slide 37
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 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 cant
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.
Slide 38
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 wedge- shaped 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. Infarction
Slide 39
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 Liquefactive
necrosis
Slide 40
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.
Gangrene
Slide 41
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. Fat necrosis
Slide 42
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. Caseous necrosis
Slide 43
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. Fibrinoid necrosis
Slide 44
Phase of necrosis It process is called karyopicnosis. Many
nuclei have become pyknotic (shrunken and dark). It process is
called karyopicnosis. After that karyorrhexis develops. Nucleus is
decomposed into small granules. 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.
Slide 45
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 The outcomes of necrosis