Zota, Vataman. General Morphopathology. 2014

Ministry of Health of the Republic of Moldova
State University of Medicine and Pharmacy

“Nicolae Testemițanu”
IEREMIA ZOTA, VLADIMIR VATAMAN
GENERAL
MORPHOPATHOLOGY
(Scientific adviser - V. Anestiade, academician)
THIRD EDITION
C entrul E ditorial -P oligrafic M edicina

C hişinău • 2014
Zota_Morfopatologia eng_2014red.indd 1 8/19/14 16:24

CZU 616-091.0
G 30
The book was approved by the Methodical Central Council of the State Medical
Pharmaceutical University ”Nicolae Testemițanu”
Ieremia ZOTA – Professor, Department of Morphopathology, State Medical and

Pharmaceutical University “Nicolae Testemitanu”
Vladimir VATAMAN – Medical doctor, Department of Morphopathology, State Medi-
cal and Pharmaceutical University “Nicolae Testemitanu”
Vasile ANESTIADE - Professor of Pathobiology, Academician, Academy of Sciences
of Moldova
Mihail PARNOV - Lecturer, Department of Morphopathology, State Medical and
Pharmaceutical University “Nicolae Testemitanu” - the English
version of the text.
General morphopatology / Ieremia Zota, Vladimir Vataman,

Vasile Anestiade [et al.]; sci. adviser: V. Anestiade; Min. of Health
of the Rep. of Moldova, State Univ. of Medicine and Pharmacy
"Nicolae Testemiţanu". – Chişinău: Lumina, 2014 (Tipografia
FOXTROT). – 236 p.
Bibliogr.; p. 231. – 350 ex.
ISBN 978-9975-65-369-5
616-091.0
G 30
© Design & Prepress: Veaceslav Popovschi
© CEP Medicina, 2014

ISBN 978-9975-65-369-5 © Ie. Zota, V. Vataman, 2014

INTRODUCTION TO MORPHOPATHOLOGY Int ro du c t io n
INTRODUCTION
TO MORPHOPATHOLOGY
The morphopathology or anatomi- of tissues and organs. The sampling of
cal pathology (from the Greek –morph tissular material is made using various
– form, pathos – suffering, disease and investigation methods:
logos – science) studies morphological a) biopsy;
changes that occur in the human body b) examination of postoperative
during various diseases. Morphologi- pieces, including those of pla-
cal lesions can be at different structural centas;
levels: macroorganism, system, organ, c) necropsy.
tissue, cellular, intracellular, molecular. Nowadays, there is an obvious in-
Morphopathology is a fundamental dis- crease of intravital morphopathological
cipline of medical education, being the investigations (biopsies and postopera-
main link between clinical and funda- tive material) in the global medical prac-
mental disciplines. tice. About 80% of the working time of a
The role of anatomical pathology in pathologist is dedicated to the diagnosis
medical practice is extremely important, of diseases and pathological processes
particularly in making a diagnosis, cor- based on the study of biopsic and sur-
rect interpretation of clinical symptoms, gical material, placentas and cytopatho-
choice of therapeutic tactics, verification logical pieces. The intravital morpho-
of the correctness of diagnosis and effi- logical diagnosis is the most exact of
cacy of treatment during the evolution all medical diagnostic options. It may
of diseases. The identification of the influence decisively the quality of clin-
3  G E N E R A L M O R P H O P A T O L O G Y IEREMIA ZOTA, VLADIMIR VATAMAN

morphological substrate of diseases is ical diagnosis and treatment, especially
performed by studying structural lesions in oncology.
BIOPSY
BIOPSY (from the Greek bios – life Only the histopathological inves-
and opsis – vision, image) definition: tigation can determine whether a
sampling of tissue fragments or organs tumor is benign or malignant; in
from a living organism, for microscopic case of malignant tumors, their
examination, with the purpose of mak- histological form is identified, for
ing a diagnosis (“operation for diag- example, squamos cell carcinoma
nosis”). Nowadays, biopsy is the main or glandular cancer (adenocarci-
field of diagnostic activity of patholog- noma); the cell variant of sarco-
ical service. The main goals of biopsy ma, melanoma, etc.;
are the following: c) staging of some diseases; it refers
a) making an exact diagnosis of a primarily to tumors – establish-
disease; ment of the stage and degree of
b) identification of the benign or histological differences of ma-
malignant nature of tumor lesions. lignant tumor, which definitely

I ntrodu c ti o n INTRODUCTION TO MORPHOPATHOLOGY
influence the therapeutic ap- completely, with the intact sur-

proach and prognosis. The his- rounding tissue, this intervention
tological examination is of great having also a therapeutic effect;
importance in revealing cancer 2. endoscopic biopsy – collection
metastases in regional and dis- of tissue material from tubu-
tant lymph nodes, in assessment lar/ hollow organs by means of
of primary tumor extension. This an endoscope (a long, flexible,
information is necessary to classi- thin tube made of optical fiber
fy tumors according to the TNM and equipped with illumination
criteria (tumor-nodus-metasta- system), which permits visual-
sis). It is also important to assess izing the inner surfaces of cavi-
the severity of morphological tary organs, after its introduction
lesions in non-tumoral diseases through natural orifices. It is ap-
of parenchymatous organs, for plied in biopsy of organs acces-
example, those of liver, kidneys sible to endoscopy under visual
(chronic hepatitis, glomerulone- control, for example, endoscopic
phritis etc.); biopsy of esophagus, stomach,
d) collection of cells for cytopatho- colon, bronchi, urinary bladder,
logical investigation and for cel- abdominal cavity (laparoscopic
lular cultures. biopsy);
There are several types of biopsies. 3. curettage biopsy – obtaining tis-
They depend on the type of the organ sue material by abrasion (scrap-
(parenchymatous or hollow), character ing) of the mucosal surfaces or
of lesions (superficial or deep) and the of other superficial lesions with
quantity of tissue necessary for histo- some curettes, for example, the
pathological or cytopathological exam- diagnostic curettage of the en-
ination. At present, a biopsy sample can dometrium, cervical canal, buccal

be collected from any organ or tissue of mucosa, skin;
the human body. The biopsy is sampled 4. needle aspiration biopsy – sam-
from tumor formations in the majority pling of biopsy by means of sy-
of clinical cases. Biopsy of macroscopi- ringes or special devices with a
cally unchanged tissues is also used, for fine needle (0.5-0.8 mm diame-
example, the skin biopsy in case of vas- ter) or a cutting needle (1.5-2.5
culitis, skin or buccal mucosa in case of mm diameter). It is used to obtain
amyloidosis, or biopsy of skeletal mus- a biopsy from deep organs/tissues,
cles in case of myositis or degenerative for example, from liver, kidneys,
diseases, etc. thyroid gland, bone marrow, pros-
Biopsy types: tate; the access is transcutane-
1. surgical biopsy – surgical collec- ous, while in prostate biopsy it is
tion of tissue material; it can be transrectal; it is usually associat-
incisional, when only a part of ed with cell and tissue fragments
formation or pathological area is aspiration. The sample of cellular
sampled, and excisional, when material is obtained by fine needle
the pathological area is removed puncture. After that, it is spread

INTRODUCTION TO MORPHOPATHOLOGY Int ro du c t io n
on a glass slide, fixed, stained and studied by the cytopathol-
and studied by a cytopathologist. ogist. The main purpose of as-
During the puncture with a cut- piration biopsy is to determine
ting needle, a tissue fragment of benignity or malignity of a tu-
cylindrical shape, of about 2 cm mor. When necessary, a cytologic
long and 1,0-1,5 mm thick is col- biopsy may be completed with a
lected. It is subject to the usual tissue one. The most eloquent ex-
histological processing and is em- ample of aspiration biopsy is the
bedded in paraffin; microscopic biopsy of thyroid gland cysts;
pieces are studied by a pathologist. 6. intraoperative biopsy is the biop-
The puncture of organs can be sy performed during a surgical in-
made directly, under the control tervention, in order to specify the
of palpation or imaging guidance diagnosis, extent of lesions, degree
(echographic, computer-imag- of penetration into tissues, some-
ing), particularly in case of some thing that is very important for a
deep intra abdominal tumors. In correct surgical act (assessment of
addition to making an exact diag- the volume of an organ resection).
nosis of some tumors, the needle The histopathological examination
aspiration biopsy is widely-used in is performed on the spot, taking
various non-tumoral pathologies 15–20 minutes, sections being per-
of liver and kidneys, in order to formed at a freezing microtome
determine the degree of affection with inclusion on ice.
and the stage of the pathological Besides the microscopic examina-
process (chronic hepatitis, cirrho- tion of sampled tissues (cells), these can
sis of the liver, glomerulonephritis be also subject to some histochemical,
etc.); immunohistochemical, luminescent

5. aspiration biopsy is the collection microscopical, ultramicroscopic anal-
of tissue material from cavities, yses and other techniques of investi-
by aspiration of the fluid content, gation. In many cases, more repeated
which is then centrifuged and the biopsies are performed, in order to
sediment rich in cells is spread on monitor the development of tumors
a glass slide, like a smear, stained and the efficacy of treatment.
EXAMINATION OF POSTOPERATIVE PIECES
According to the current require- scopic description of postoperative pie-

ments, all tissue and organs fragments, ces and a record of all lesions visible to
entire organs or parts of the body (for the naked eye. Then, tissue fragments are
example, the limbs) removed during sur- sampled from all the revealed lesions, in-
gical interventions, as well as placentas, cluding, as much as possible, in the same
must be sent to a pathology department, fragment, both pieces of the changed ma-
where they are exposed to macroscopic croscopic tissue and of the normal one.
and microscopic examination. First of all, This is necessary to assess the correct-
the pathologist makes a detailed macro- ness of resection of an organ, especially

I ntrodu c ti o n INTRODUCTION TO MORPHOPATHOLOGY
in tumor pathologies, as well as to esti- stained by different methods. The speci-

mate the reaction of lesion adjacent tissu- mens are studied by a pathologist, who
es. Then, tissue fragments are processed makes an extended histological descrip-
histologically and embedded in paraffin tion and, on the basis of macroscopic and
blocks. After that, microscopic sections microscopic data, establishes a definitive
are removed from paraffin blocks, being pathologic diagnosis.
POSTMORTEM EXAMINATION (NECROPSY)
NECROPSY (from the Greek ne- confrontation results of the anatomo-

kros – dead and opsis – vision, image). pathological diagnosis with the clini-
Although recently the number of cal one, and, in case when they do not
autopsies has been decreasing, they con- match – points out the possible reasons
tinue to be an important method of dia- of identified medical errors. The anato-
gnosis and control of medical act. There mo-clinical confrontation and the iden-
is no other objective method to verify the tification of medical errors constitute a
correctness of diagnosis and treatment permanent training and improvement
than the necropsy of the deceased. school for physicians, regardless of their
Necropsy is the direct research of speciality.
morphological lesions on cadaver, occur- Another way to collect the mate-
red during diseases. Directly during the rial for anatomopathological study of
necropsy, macroscopic changes in all the diseases is the experimental one. Cre-
tissues and organs are studied thorou- ation of experimental models has con-
ghly. Based on this study, a presumptive tributed significantly to the knowledge
anatomopathological diagnosis is esta- of the pathogenesis and morphogenesis
blished (by agreement with the treating of many human diseases. Besides this,
physician, whose presence is obligatory modelling of some diseases on animals

at necropsy). Subsequently, fragments gives adequate possibilities to test medi-
from all the organs are sampled and cinal drugs and some new surgical tech-
subject to histopathological processing. niques of treatment.
Histological specimens are studied mi- The basic principle of modern
croscopically, and, whenever necessary, pathology is the anatomo-clinical orien-
other additional histochemical, bacte- tation. It is a morphological discipline,
rioscopic and luminescent microscopic from a methodical point of view, but it
methods are applied. At the end of all is a clinical discipline, from the point
these investigations, a final anatomo- of view of medical practice. This mutu-
pathological diagnostic is established al combination places pathology in the
and recorded in a necropsy protocol and middle of human medicine. Pathology
in the medical history of the patient. knowledge is indispensable for the study
A necropsy protocol also includes the of other clinical disciplines in medical
clinical–anatomical epicrisis, in which education, as well as for daily practical
the pathologist motivates the diagnosis, activity of clinical doctors.
indicates the cause of death, ascertains

DEATH OF THE BODY Chapte r 1
DEATH OF THE BODY

Death is the final and irreversible Since various tissues and organs have
cessation of vital functions of the body. different sensitivity to anoxia, the death
The final interruption of biological pro- process takes place in a certain dynamic,
cesses at tissues and organs level leads in stages. The real (irreversible) death is
to their death and disintegration with preceded by a series of phenomena, cal-
transformation of the living, organic led terminal states, which means the fi-
matter into dead, inorganic matter and nal period of the disease, a state between
of the human body into a corpse (lat. life and death, when deep disorders of
cadaver). According to the causative fac- homeostatic parameters of the body ap-
tor, the following types of death can be pear. According to the clinical point of
distinguished: a) natural; b) violent; c) view, the periodization of terminal states
caused by diseases. is divided in preagonia, agonia and clini-
The natural death (physiological) cal death, each of them requiring diffe-
occurs as a result of natural wearing of rent medical approaches. The moment
the body in people of advanced age. of death of the entire body is considered
The violent death is caused by some the moment when the death of the bra-
external factors: traumatic, physical, in is established (the cerebral death - the
chemical, mechanical etc. Cases of vio- equivalent of the body’s death). This aspect
lent deaths are studied by forensic me- is especially important in the context of
dicine service. sampling of the organs/tissues from the
The death caused by diseases (pathologi- corpse, with the purpose of transplanta-

cal death) is conditioned by changes that tion.
are incompatible with life, developing Depending on the reversible or irre-
within various diseases and pathologi- versible character of vital activities chan-
cal processes. Usually, they settle slowly, ges of the body, we distinguish clinical
reducing the vital functions of the body and biological death. Clinical death is
gradually. Cases of death caused by di- characterized by cessation of respiration
seases are studied by the anatomopatho- and of blood circulation (cardiac con-
logical service. tractions). The duration of clinical death
Sometimes, sudden, unpredictable is ~ 5–6 min. – it is the duration of cortex
death takes place, occurring unexpec- survival in conditions of anoxia. During
tedly, apparently in full health, within 1 clinical death, the respiration and blood
hour of the onset of clinical symptoms. circulation are lacking, but the cellular
The cause may be ischemic cardiomyo- metabolism continues through anaero-
pathy, first of all myocardial infarction bic glycolysis. The stocks of glycogen in
and rarely aortic stenosis, congenital or the brain deplete gradually and irrever-
acquired disorders of the heart conducti- sible lesions occur in the nervous tissue –
on system, cardiomyopathies, electrolyte death of cerebral cortex neurons. During
disorders etc. Cases of sudden death are the electroencephalographic examinati-
subject to forensic medical examination. on (EEG), a flat track is recorded in the

Chapter 1 DEATH OF THE BODY
frontal lobes activity (isoelectric line or hours, it reaches maximum level and in
“bioelectrical silence”). 2–3 days disappears in the same order. If
After that, biological death occurs – handled with force, the muscle rigidity
the irreversible cessation of vital activity doesn’t recover. The intensity and rapi-
of the body. The signs of certainty of dity of cadaveric rigidity establishment
biological death are: depend on the degree of development of
1) cooling of the corpse; the body musculature and of specificity
2) cadaveric rigidity; of the pathological process which prece-
3) cadaveric lividities (spots); ded the death. For example, the rigidity
4) dehydration (drying) of the corpse; appears more rapidly and is more intense
5) decomposition of the corpse. in people with a strong musculature and
The cooling of the corpse (algor in death preceded by convulsions (teta-
mortis) nus, cholera, intoxication with strych-
The decreasing of temperature starts nine). The mechanism consists in de-
on the surface of the body and becomes composition of adenosine triphosphoric
more obvious in uncovered places. Gra- acid (ATP) in muscles after the death,
dually, the body temperature is leveled accumulation of lactic acid and the in-
with external environmental tempera- crease of actinomyosin viscosity, leading
ture. The rapidity of the process depen- to hardening of muscles. The resolution
ds on the temperature and humidity of is based on the autolysis of muscle fibers.
the atmospheric air, the volume of the Cadaveric lividities (spots) – spots
corpse, the thickness of the subcutane- of purple color on the declivous parts of
ous adipose layer and the specificity of the body. The localization of the spots
the pathological process. The cooling of depends on the position of the body at
the corpse occurs due to the stopping of the moment of death and, as a rule, they
heat production in the body, as a result lack in places exposed to pressure. They
of blood circulation cessation, suppres- begin to appear in 3–6 hours after death.
sion of oxidative processes, and heat loss At first, they disappear at digital pressu-
in the external environment. Generally, re and reappear after its cessation, and in
it is considered that the temperature of 18–24 hours they have a red–rose color
the corpse drops one degree per hour, if and do not disappear at digitopressure.
external environmental temperature is The mechanism consists in redistribu-
half of body temperature. This rhythm tion and accumulation of blood in the
depends, to a great extent, on the tem- vessels of declivous parts of the body, as
perature of the body at the moment of a result of cessation of circulation and
death and the temperature of the exter- gravity (cadaveric hypostasis). In 18–24
nal environment. hours after death, a cadaveric imbibi-
Cadaveric rigidity (rigor mortis) tion occurs, generated by the erythro-
Hardening and stiffness of the mus- cytes hemolysis and the diffusion of
cles appear in 2–5 hours after the death plasma in the tissues. The blood in the
and spread gradually in craniocau- corpse is accumulated in veins, arteries
dal dimension, from the face muscles being almost empty. The passing of the
(masseter and mimic muscles) to lim- blood from arteries to the veins is de-
bs, involving all muscle groups. In 24 termined by the rigidity of the smooth

DEATH OF THE BODY Chapte r 1
muscles of the arterial walls. The post autolysis – softening and liquefaction
mortem coagulation of the blood caused of cells and tissues, under the action
by the suppression of blood circulation of own enzymes. Glandular organs get
takes place in veins and in the right ca- autolysed faster, first of all the pancre-
vities of the heart. The blood does not as, liver, gastrointestinal and bronchial
coagulate in cases of asphyxia. Cadaver mucosa, the cells of which are rich in
clots are more numerous, when death hydrolytic (proteolytic) enzymes. Gra-
occurs slowly, and less numerous, when dually, putrefaction processes are associ-
it occurs suddenly. Intensity and color of ated, caused by aerobic and anaerobic
cadaver spots depend, to some extent, on microbial flora, which is more abundant
the previous pathology. For instance, in in the intestine. Putrefaction intensifies
cases of chronic heart failure, the spots cadaveric autolysis and is more evident
are well marked and intensely colored, in the abdominal cavity. Microbes pro-
while in anemias and in cachectic con- duce hydrogen sulfide, which reacts with
ditions they are weakly pronounced. disintegrating products of hemoglobin,
Cadaveric dehydration (drying) forming sulfhemoglobin of green color.
of tissues, first of all, mucosas, skin and This gives the respective color to the tis-
eyeballs. The skin, especially at the le- sues and the abdominal wall. The green
vel of scrotum and digital pulp gains a spot of putrefaction appears in appro-
parchment aspect. Mucosas, particularly ximately 24 hours from the moment of
of the lips, become dry, wrinkled, and death. Putrefaction gases penetrate the
dense, scleras lose their luster, cornea tissues and organs, determining the ap-
becomes opalescent, and a whitish spot pearance of cadaveric emphysema. The
appears at the level of the pupil (corneal rapidity and the intensity of autolysis
clouding). These changes can be expla- and putrefaction depend on the tem-
ined due to cessation of circulation and perature of the external environment

evaporation of water from the surface of and on the specific character of patho-
the body. The intensity of dehydration logical process, being better marked in
of the corpse depends much on the tem- cases of infectious diseases, septicemias,
perature and humidity of external envi- peritonitis. Keeping the corpse at low
ronment. temperatures diminishes the effects of
Decomposition of the corpse putrefaction and embalming provides
occurs as a result of corpse autolysis long-term conservation.
and putrefaction processes. Cadaveric

Chapter 2 CELLULAR AND EXTRACELLULAR REVERSIBLE LESIONS
CELLULAR AND EXTRACELLULAR

REVERSIBLE LESIONS
Lesion or alteration is the change changes, but, when the pathogenic fac-
of the structure of the cells, intercellu- tor acts permanently, or has a major in-
lar substance, tissues and organs, which tensity, irreversible lesions, which may
occurs in pathological conditions and result in cellular death, occur. The diffe-
manifests itself by disturbing their vi- rence between reversible and irreversible
tal activity. These changes can be cau- cellular lesions is more of quantitative
sed by excessive physiological stimuli or nature. A reversible lesion is insignifi-
by pathological factors. The severity of cant, superficial, and after removement
cellular/tissular lesions depends not only of the harmful factor, the cell returns to
on the specificity, length and intensity its normal state. But, if the alteration is
of action of the pathogenic agent, but severe or persistent, the restoration of
also on many other factors referring to the cell is impossible and the lesion be-
the cells themselves, for example their comes irreversible. The transition from a
vulnerability, sensitivity to aggressive reversible lesion to an irreversible one is
actions, degree of differentiation, blood gradual and happens when the adaptive
supply, nutrition, antecedent condition, potential of the cell is exhausted.
as well as the capacity to adapt to new So, the cellular response to harmful
conditions of existence. In most cases, as actions is manifested in the appearance
a response to a harmful agent, adaptive of a wide range of morphological chan-
processes develop in the impaired cells, ges, which can be grouped as following:
resulting in a new condition of struc-  adaptive processes;
tural–functional stability (a state of ho-  reversible lesions;
1 0  G E N E R A L M O R P H O P A T O L O G Y IEREMIA ZOTA, VLADIMIR VATAMAN
meostasis), which ensures the survival  irreversible lesions;

and the functional activity of the cells  cellular death.
in the modified microenvironment. If Adaptive processes (atrophy, hyper-
the limits of the adaptive response are trophy, hyperplasia and metaplasia) are
exceeded, a cellular/tissular lesion takes tackled in the chapter “Adaptive – com-
place, being reversible up to a certain pensatory processes”.
level of progressing of morphological
2 . 1 . C AU S E S O F C E L LU L A R
E X T R A C E L LU L A R L E S I O N S
The causes of reversible and irrever- cellular death. Etiological factors of cellu-
sible lesions of cells and extracellular ma- lar lesions vary from severe mechanical
trix are similar. Initially, most of causative traumas with crushing of tissues, wounds,
factors cause reversible lesions, but, if the up to molecular defects at genes level,
harmful factor has a severe and prolon- which are the basis of congenital meta-
ged action, the changes progress and the bolic diseases. Etiological factors of cellu-
cell achieves a “non–return” point, when lar lesions can be divided in many groups,
irreversible lesions occur, which result in and namely:

CELLULAR AND EXTRACELLULAR REVERSIBLE LESIONS Chapte r 2
1. Hypoxia (anoxia) caused by disturban- harmfully on lipids, proteins and cellu-
ces of cardiovascular and respiratory lar DNA. Example: solar burns of the
systems, anemias, intoxications with skin in excessive ultraviolet radiation.
carbon monoxide etc. Hypoxia indu- 3. Chemical agents: exo- or endogenous
ces disturbances of aerobic breathing toxins, drugs, medicines. Example: li-
in the cells, the decreasing of synthesis ver dystrophy and its necrosis in case of
of ATP and the compensatory activa- intoxications with poisonous mushroo-
tion of anaerobic glycolysis. A rapid ms.
exhaustion of intracellular resourses of 4. Infectious agents: viruses, bacteria,
glycogen occurs, as well as an accumu- rickettsias, fungi, parasites. Example:
lation of lactic acid, a decrease of pH the lesion of respiratory tract mucosa
and an impairment of the activity of by the influenza virus.
most cellular enzymes. A reduction of 5. The immune responses (autoimmune).
ATP synthesis by more than 5–10%, in Example: pathology of the cell nuclei
comparison with the norm, influences in disseminated lupus erythematosus,
many critical cellular systems, and, first caused by antinuclear and antinucleolar
of all, the membrane sodium pump, autoantibodies.
which causes the intracellular accumu- 6. Impairment of the trophic function of
lation of sodium, water retention and the neuroendocrine system. Example:
tumefaction of the cell. Example: the the dystrophy and atrophy of tissues in
reduction or suppression of the arterial innervation disturbances.
blood supply to myocardium, as a result 7. Genetic disorders (genetic or chromo-
of stenosing atherosclerosis of coronary somal defects). Example: hereditary
arteries, causes ischemic dystrophy or enzymopathies or thesaurismoses (sto-
myocardial infarction. rage diseases).
2. Physical agents: mechanical, thermal 8. Nutritional disorders: insufficiency or

traumas, radiations. In some cases, a excess of some substances in nutrition
direct destructive action of the causa- (iron, vitamins, proteins, lipids, etc.).
tive factor takes place on tissues/cells, Examples: fatty dystrophy of the liver
in others, like ultraviolet and ionizing in cases of fat misuse in nutrition, de-
radiation, the pathogenic effect is ma- velopment of diabetes mellitus type II
nifested by an excessive accumulation in obesity.
of the oxygen free radicals, which acts
2.2 MORPHOLOGY OF CELLULAR

AND EXTRACELLULAR REVERSIBLE LESIONS
Cellular and extracellular reversible Dystrophy (cellular/extracellular
lesions are also called dystrophies or de- reversible lesion) is a pathological pro-
generative processes (degenerescences). cess, caused by disturbances of the cellu-
The notion currently used of “cellular metabolism (intercellular), inducing
lar/extracellular reversible lesions” structural changes. All pathological
is identical with the classical notion processes start at the molecular level
of “dystrophies”. Further on, the term and any cellular response to an aggres-
“dystrophy” will be used. sive action is first of all manifested by

cellular metabolic disturbances. By pro- stances which are encountered in

gressing, they lead to structural changes physiological conditions;
noticeable at the level of cellular com- c) storage in cells or/and in intercellu-
partment or intercellular structures. lar spaces of some usual substances,
Cellular lesions ensue from functional but in unusual places;
and biochemical disturbances of one d) appearance and storage in the cells
or more cellular components. The most or/and in interstitium of some sub-
important and sensible to harmful sti- stances that are not encountered in
muli are: 1) mitochondria, which ensure the organism in normal conditions.
the breathing and energetic resources These quantitative and qualitative
of the cell; 2) the cellular membrane, changes of different metabolic products
which regulates the ionic and osmotic can be made through the following
homeostasis of the cell; 3) the cytoske- morphogenic stereotype mechanisms:
leton, which ensures such cell functions 1. Infiltration – excessive pene-
like support, transport, contraction and tration in cells (intercellular spaces) of
motor; 4) the synthesis of proteins and some metabolic products from blood,
5) the cellular genetic apparatus. The lymph, urine and their further storage,
possibilities to detect these changes de- as a result of insufficiency of enzymatic
pend on the sensibility of the applied systems to metabolize them. Example:
methods of morphological investigation. infiltration of epithelial cells of renal
Histochemical and electron microscopy tubes with glucose in diabetes mellitus
techniques allow identifying the dysme- or infiltration with lipids of the hepatic
tabolic lesions in a short time (minutes, lobules in obesity (lipemia).
hours) from the onset of the harmful ac- 2. Decomposition (phanerosis) –
tion, and, macroscopically or microsco- break down (decomposition) of some
pically, they become visible much later. complex chemical substances and the
Example: dystrophic lesions caused by storage of their components in the cells
the myocardial ischemia can be tracked or in the extracellular compartment.

by histochemical reactions in 30 minu- Example: break down of lipoproteic
tes–2 hours from the onset of ischemia complexes of membranous structures in
(histochemical methods for glycogen hypoxia, intoxications or decomposition
and oxidoreductive enzymes), while, of the glycoproteic complexes from the
by means of an optical microscope – in ground substance of connective tissue in
12–20 hours. rheumatic diseases.
Morphologically and biochemically, 3. Transformation – formation
dystrophies are manifested by quanti- of one type of metabolic products from
tative and qualitative changes of some precursor substances, common to all
metabolic products in the cells and/or types of metabolism (proteins, lipids
intercellular spaces. There may be the and glucides). Example: transformation
following variants: of the components of glucides in fatty
a) accumulation in the cells or/and in acids or of amino acids in glucides.
interstitium of some usual chemical 4. Pathological synthesis – the
substances in excessive amounts, in synthesis of some substances not usually
comparison with the norm (intra- seen in cells and tissues in physiologi-
cellular accumulations); they can be cal conditions. Example: the synthesis of
of intracellular or extracellular origin; the abnormal glycogen in some heredi-
b) decreasing of some structural sub- tary glycogenoses.

The classification of dystrophies, according to various criteria, is presented in the Table 2.1.
Table 2.1
Classification of dystrophies
Varieties of dystrophies according

Classification criterion
to the given criterion
a) Cellular (parenchymatous)
Predominant localization of
b) Extracellular (mesenchymal,
metabolic enzyme disturbances
stromal-vascular)
c) Mixed (intra- and extracellular)
a) Proteic (disproteinoses)
Type of altered metabolism b) Lipidic (dislipidoses)
c) Glucidic
d) Mineral
a) Systemic (generalized)
Extension of dystrophic lesions
b) Localized
Mechanisms of development a) Acquired
(role of genetic and acquired factors) b) Hereditary (congenital)
2 . 3 . C E L LU L A R L E S I O N S
( PA R E N C H Y M ATO U S C E L LU L A R D Y S T RO P H I E S )
Metabolic disturbances in this group may be qualitative and quantitative.
of dystrophies take place in parenchyma- According to the impaired type of me-

tous cells, which perform the specialized tabolism, parenchymatous dystrophies
function of these organs. Morphological are subdivided into proteic, lipidic and
changes take place both at the level of glucidic dystrophies (Table 2.2).

cytoplasm and at the nucleus level and Table 2.2
Classification of cellular dystrophies

ØØ granular dystrophy
ØØ cellular hyaline dystrophy
ØØ hydropic dystrophy
I – Proteic dystrophies ØØ keratin dystrophy
ØØ hereditary dystrophies with impairment
of amino acids metabolism
ØØ fatty cellular dystrophy (steatosis)

II – Lipidic dystrophies ØØ hereditary systemic lipidoses.
ØØ glycogenic dystrophy
III – Glucidic dystrophies ØØ hereditary glycogenoses
ØØ cellular mucous (mucinous) dystrophy

2.3.1. PROTEIC CELLULAR DYSTROPHIES

(CELLULAR DISPROTEINOSES)
Granular dystrophy (cloudy intu- (for example: appearance of proteinuria

mescence) develops in parenchymatous in the granular dystrophy of kidneys).
organs, such as kidneys, myocardium Consequences. Granular dystrophy
and liver. is the first sign of a cellular lesion, and
Microscopically, it manifests itself by it is reversible, if the causative factor
the presence in the cells (nephrocytes, is removed. In case the harmful acti-
cardiomyocytes and hepatocytes) of a on persists, the changes can advance to
large number of tiny proteic granules. more severe lesions, like cellular hyaline
Macroscopically, the affected organs dystrophy, hydropic or lipidic.
are somewhat larger in size and weight. The appearance of some proteic gra-
They have a weakened capsule, flaccid nules in cytoplasm of the cells can be
consistency; luster is absent, opaque and also observed in physiological conditi-
pale aspect like of boiled meat, hence its ons, reflecting the morpho– functional
name of cloudy intumescence. peculiarities of the cell (for example,
When examined microscopically, the elaboration of secretory granules in en-
cells are bigger in size, tumefied, with docrine cells of the glands, physiological
unclear margins; the cytoplasm has a resorption of proteins by the epithelium
fine granular, reticulated aspect and con- of the proximal renal tubes etc.), intensi-
tains proteic granules, small eosinophils fication of the synthesis function of pro-
spread uniformly (fig. 2–1a). teins (ex: in hepatocytes, secretory cells),
The electron microscopy detects di- hyperplasia and hypertrophy of cyto-
latation of the endoplasmic reticulum, plasmic organelles in functional over-
which contains agglomerations of pro- strain of parenchymatous organs etc.
teic masses and an insignificant tume- Cellular hyaline dystrophy (in-

faction of mitochondria (fig. 2–1b). tracellular hyalinosis) is characterized
The function of the affected organs by the appearance in the cells of some
in granular dystrophy is slightly altered homogenious, eozinophilic large dro-
a b
PM
Fig. 2–1 a, b. Granular dystrophy of the epithelium of convoluted renal tubes: a – microscopic
pattern (hematoxylin–eosin stain; ×70); b – electron microscopic image (×16000); V – vacuoles
(dilated cisternae of endoplasmic reticulum); PM – proteic masses; N – nucleus;

plets of proteic origin, occupying the Russel corpuscles, representing storages
entire cytoplasm (Fig. 2–2). Macrosco- of immunoglobulins in vesicles of rough
pically, the affected organs do not show endoplasmic reticulum of plasmocytes
any characteristic signs. The electron and hyaline cytoplasmic inclusions in
microscopy reveals a destruction of viral infections. A similar process can
Fig. 2–2. Cellular hyaline dystrophy of the epi- Fig. 2–3. Cellular hyaline dystrophy (Mallory
thelium of the proximal renal tube (hemato- corpuscles) and steatosis of hepatic cells (hema-
xylin–eosin stain; ×200). toxylin–eosin stain; ×110).
cytoplasmic organelles, homogenisati- be observed in the Alzheimer disease,
on and their change into proteic hyalin when neurofibrillary plexus constituted
structures. of cytoskeletal proteins, especially of mi-
It can be seen more frequently in crotubules and neural fibers, are formed
kidneys (epithelium of uriniferous tu- in neuronal cytoplasm.

bes) and in the liver (hepatocytes). It can It is an irreversible process leading to
be observed in kidneys in cases of mas- focal or entire necrosis of the cell. Cli-
sive proteinuria, in glomerulonephritis, nically, it is manifested by severe distur-
renal amyloidosis, diabetic glomerulo- bances of the organ’s function (for ex:
pathy, paraproteinemic nephrosis, into- the appearance of proteins and hyaline
xications etc., when the permeability of cylinders).
glomerular filter increases and an exces- Hydropic dystrophy (vacuolar) ma-
sive reabsorption of proteins from the nifests itself by the appearance of some
urinary filtrate occurs. Similar lesions vacuoles filled with cytoplasmic fluid in
appear in hepatic cells, in case of alcoho- the cytoplasm of the cells. At the micro-
lic hepatitis and alcoholic cirrhosis - so scope, vacuoles are optically empty, ro-
called Mallory corpuscles or the alco- und or oval with pale nucleus (Fig. 2–4).
holic hyaline – intracytoplasmic hyaline It can be seen both in parenchymatous
accumulations of proteins (cytokeratins) organs and in the skin (epidermis). Ma-
of intermediate fibers, which may be croscopically, the affected organs are sli-
considered as a result of cytoskeleton’s ghtly changed.
alteration under the action of alco- The main mechanism of vacuolar
hol (Fig. 2–3). Other examples are the dystrophy is the disturbance of the hy-

glycogen and lipids (the absence of stai-

ning confirms the diagnosis).
Vacuolar dystrophy is an irreversible
process, resulting in a colliquative necro-
sis of the cell. It may result in a distended
dystrophy of the cell as a manifestation
of a focal colliquative necrosis. After
that, severe functional disturbances ap-
pear in the respective organs. For exam-
ple, hydropic dystrophy of epithelium of
renal tubes is observed more frequently
in nephritic syndrome, characterized by
deep proteinuria and edemas. Vacuolar
Fig. 2–4. Hydropic dystrophy of the epithelium
dystrophy of myocardium is manifested
of convoluted renal tubes (hematoxylin–eosin
by a considerable reduction of the heart
stain; ×70).
dro-electrolyte and proteic metabolism contractility function.
with change of intracellular colloid-os- Hydropic dystrophy is noted in in-
motic pressure, which leads to penetra- fectious diseases (mostly in viral hepa-
tion of water into the cell or the impair- titis), intoxications (with phosphorus,
ment of elimination of it from the cell, arsenic, carbon tetrachloride), inanition
during the oxido-redox processes. An states, avitaminoses, under the action of
excessive accumulation of water leads penetrant radiation etc.
to destruction of cellular ultrastructures Keratin dystrophy (cornous) is ob-
and appearance of vesicles filled with served in the skin and mucosa covered
cytoplasmic fluid (cell distention). This with squamous and transitional epithe-
fluid accumulates in the vesicles of en- lium. It shows an excessive formation of
doplasmic reticulum and in the mito- keratin in the pluristratified cornified
chondria (Fig. 2–5). A certain diagnosis squamous epithelium (hyperkeratosis)

of hydropic dystrophy can be made only or an appearance of keratin in epithe-
after the staining of microspecimen for lium of mucosas, which is not cornous
under normal conditions (leukoplakia).
Macroscopically, in hyperkeratosis
foci, the skin is thickened, dry and has an
aspect of fish scales or corns (Fig. 2–6a).
Microscopically, the cornous layer of the
epithelium is thickened considerably, as
N
a result of an excessive formation of ke-
ratin (Fig. 2–6b). The chronic inflamma-
tion, viral infection, avitaminoses (par-
ticularly the lack of vitamin A), chronic
M
irritations, some skin developmental
ER disturbances, e.g.: congenital hyperkera-
tosis or the ichthyosis (from the Greek
ichtys - fish + osis - pathological process)
Fig. 2–5. Hydropic dystrophy of hepatic cell are significant in the etiology of lesion.
(electron microscopy ×7000); ER – endoplasmic Generalized congenital ichthyosis is a
reticulum; M – mitochondria; N – nucleus. pathology that is incompatible with life.

Fig. 2-7. Leucoplazia mucoasei bucale.
Fig. 2–7. Leukoplakia of buccal mucosa.
layer is formed from keratinized, enu-

cleated cells, and is covered with a ke-
b ratin layer. Leukoplakia can also appear
on mucosas covered with unistratified
Fig. 2–6 a, b. The skin hyperkeratosis: a – ma- epithelium, if squamous metaplasia of
croscopic aspect; b – microscopic pattern (he- mucosas took place initially (in bronchi,
matoxylin-eosin stain, ×70).
stomach, intestines, and endometrium).
Leukoplakia is observed in oral Chronic inflammations, chronic irri-
cavity mucosa, tongue, lips, pharynx, tations (smoking), traumatisms etc. are
larynx, vaginal portion of the uteri- the most frequent causes of leukoplakia,
ne cervix, vagina, and urinary bladder. which is considered to be a precancerous

Macroscopically, it shows some slightly lesion.
prominent, well-delimitated plaques of Keratin dystrophy can advance
whitish color and a smooth or irregular towards restoration of the affected tissue
surface, which can reach some centi- or necrosis of the cells. The function of
meters in diameter (Fig. 2–7). Micro- the skin and mucosas in the deteriorated
scopically, the pluristratified squamous areas is severely impaired.
epithelium is thickened; the superficial
2.3.2. LIPIDIC CELLULAR DYSTROPHIES
(CELLULAR LIPIDOSES)
The metabolic disturbances of neutral steatosis), without a limiting membrane.
lipids or steatosis of the parenchymato- Optically, the lipidic droplets appear to
us organs are the most frequent of this be empty, in pieces processed in paraffin,
group of dystrophies. Macroscopically, since lipids dissolve in alcohol, chloro-
the affected organs have an increased form etc. To keep the lipids in tissular
volume and weight, a flaccid consistency fragments, their contact with lipophilic
and a yellow aspect (claylike). Microsco- reagents during histological processing
pically, steatosis appears in cytoplasm of is avoided and sections are made in fre-
the cells like some droplets of neutral fats ezing microtome.
of various sizes (macro or microvesicular

The following methods of staining by the inhomogeneous character of the

are applied to identify the lipids: fatty dystrophy, because deposition of li-
 Sudan III or Scharlach - the lipids pids takes place mainly around veins and
are stained in red; venules. This focal, segmentary charac-
 Sudan IV or Osmic acid – the lipids ter of lipidic inclusions occurs in case of
are stained in black; a moderate hypoxia of myocardium. In
 The Nile blue stains fatty acids in severe lesions, for example in severe ane-
dark-blue and neutral fats - in red. mias, the myocardial steatosis is diffuse.
The heart in fatty dystrophy is in- Under the microscope, small or bigger
creased in size, the compartments are droplets of lipids can be revealed in car-
enlarged, dilated, the myocardium has a diomyocytes cytoplasm, which are colo-
flaccid consistency and, on the necropsy red in yellow–red, when processed with
table, it extends and widens; it is opaque, Sudan III (Fig. 2–8b). During electron
pale–yellowish on cross section. Under microscopic examination, a lipidic in-
the endocardium, mostly in the region clusion has a characteristic white–black
of papillary muscles, an alternation of striation and adheres to membranes of
some yellowish fattish striae can be no- cytoplasmic organelles, mostly of mito-
ted, with areas of usual color, the heart chondria (Fig. 2–8c). The membranes
a b
Fig. 2–8 a, b, c. Fatty dystrophy of myocardium

MF M
L (myocardial steatosis): a – macroscopic aspect
(“tiger heart”); b – microscopic pattern (Sudan
M III stain; ×70); c – electron microscopic image
L (×21000); L – lipidic inclusions, M – mitochon-
L dria, MF – myofibrils.
become dim and destroyed in areas of
contact with lipidic inclusions.
It frequently happens in chronic car-
diovascular insufficiency (rheumatic or
L congenital valvulopathies, cardiosclerosis,
c
cardiomyopathies), anemias, severe infec-
getting an aspect similar to the skin of a tious diseases, intoxications (with etha-
tiger (“tiger heart”, Fig. 2–8a). The tiger nol, phosphorus) etc. It is particularly
skin aspect of myocardium is explained characteristic for diphtheric myocarditis

and severe anemias. The predominant ged up to 3–4 kg, being 3–5 times bigger
morphogenetic mechanism is decompo- than the normal one. The lobular pattern
sition or lipophanerosis – the splitting of is kept or even emphasized (in cases when
lipoproteic compounds of intracellular the dystrophic process occurred only in
membranes. The contractile function of some areas of the lobules – in the centre
the heart is decreased. Myocardial ste- or at the peripheral area of the lobule), or
atosis is considered as a morphological it may be erased, dim in severe dystrophi-
substrate of functional decompensation es with diffuse steatosis of hepatocytes;
of the heart. the final case is macroscopically similar
The liver in steatosis has an increa- with the “goose liver” (Fig. 2-9 a). Micro-
sed volume and mass, the fibrous capsule scopically, initially, the granules of lipids
is distended and smooth, the borders are appear in hepatocytes (pulverulent stea-
rounded, the consistency is soft, pasty, of tosis), subsequently - small droplets (mi-
a yellowish color on section (claylike as- crovesicular steatosis), which confluence
pect), homogenous or spotted, a layer of in dynamics, forming large droplets (ma-
fat remaining on the blade of necropsy crovesicular steatosis). In severe steatosis,
knife. The mass of the liver can be enlar- the lipids blend and form a bigger dro-

a b
L
L
c d
Fig. 2–9 a, b, c, d. Fatty dystrophy of the liver (hepatic steatosis): a – macroscopic aspect; b, c – mi-
croscopic pattern (b – hematoxylin–eosin stain, c – Sudan III – stain; ×70); d – electron microsco-
pic image (×10000): L – lipidic inclusions; N – nucleus.

plet, pushing the nucleus to the edge and etc.), tissular hypoxia (in heart failure,
the hepatocyte becomes similar to the severe anemias, pulmonary diseases) etc.
fatty cell (adipocyte). A rupture of mem- In clinical practice, the liver steatosis in
branes of hepatocytes and formation of alcoholism and diabetes mellitus associ-
some lipidic cysts may occur. Steatosis is ated with obesity are significant.
observed more frequently in peripheral The predominant morphogenetic
areas at the level of hepatic lobule, and mechanism of peripheral areas of ste-
more rarely - around the central vein and, atosis (peripheral or periportal steatosis)
in severe lesions, it becomes diffuse (Fig. is the infiltration and it is observed in
2–9 b and 2–9 c). Electronomicrosco- cases of hyperlipidemia (fats penetrate
pically, it can be established that lipidic the liver with the blood of portal vein
droplets are mainly placed in the perinu- and infiltrate the peripheral areas of the
clear area of hepatic cells (Fig. 2–9 d). lobules first) and of centrolobular areas
The most frequent causes of hepa- (centrolobular steatosis) – decomposition,
tic steatosis are the lipidemia (in obesity, which may occur as example, in progres-
excess of fat in the diet, chronic alcoho- sive hypoxia of the liver.
lism, diabetes mellitus, hormonal disor- The function of the liver in fatty
ders), hepatotropic intoxications (with dystrophy remains normal for a long
phosphorus, carbon tetrachloride, etha- time. When the action of harmful factor
nol, chloroform etc.), nutrition disorders persists, necrosis processes associate and,
(lack of proteins or lipotropics factors, gradually, a micronodular cirrhosis begins
avitaminoses, digestive tract diseases (portal type).
2.3.3. GLUCIDIC CELLULAR DYSTROPHIES
The following methods of staining In order to keep the glycogen, frag-
are used for the histochemical identifi- ments of tissues are fixed in alcohol in
cation of glucides: order to avoid the contact with water,

 PAS reaction (periodic–acid–Schiff) - which dissolves the glycogen. Glucides
to reveal the amount of glucides – it metabolism disturbances are subdivided
is colored in red; in order to identify into:
the glycogen, the amylase – an enzy-  glycogenic dystrophy;
me which dissolves the glycogen  dystrophy of glycoproteins or
- is applied additionally on colored parenchymatous mucinous dystrophy.
sections with PAS reaction. The di- Glycogenic dystrophy manifests
sappearance of staining after being itself as an excessive accumulation of
processed with amylase confirms the glycogen in the cytoplasm of the cells
presence of glycogen; and it can be seen more frequently in
 reaction with Best carmine to trace diabetes mellitus. In kidneys, changes
out the glycogen (it is colored in red); appear as a result of hyperglycemia and
 reaction with toluidine or alcian blue glucosuria, determined by the impair-
to identify glycosaminoglycans, stai- ment of the process of taking (using) of
ned in red–purple (metachromatic glucose by tissue, related to insufficient
– the tissue appears colored differently secretion of insulin by beta cells of the
compared to the staining solution), the pancreas isles (Langerhans). Renal tubes
normal tissue being colored in blue epithelial cells have a clear, vacuolized
(orthochromatic – the color of the stain). cytoplasm, and, at Best carmine staining,

glycogen granules of different sizes, red- secretory canals and a formation of cys-
colored can be revealed (Fig. 2–10). The tic cavities. As a result of parenchyma-
cells of the thin segment and distal por- tous mucinous dystrophies, necrosis
tions of the convoluted tubes are affec- and desquamation of the affected cells
ted most of all; glycogen granules can be occur. Sometimes, mucoid or pseudom-
Fig. 2–10. Glycogenic infiltration of epithelium Fig. 2–11. Mucinous gastric cancer with “signet
of renal convoluted tubes in diabetes mellitus ring” cells (hematoxylin–eosin stain; ×110).
(carmine stain; ×70).
ucin substances accumulate in glandular
structures.
seen in the tubes lumen too. The main When condensed, they have a collo-
morphogenetic mechanism of renal id aspect (colloidal dystrophy) with a
glycogenic dystrophy is the infiltration, gelatinous consistency. It can be seen in
as a result of glucosuria. A thickening of colloid goiter, adenomas and colloid car-
basement membranes of capillaries and cinomas of the thyroid gland.
depositions of polysaccharides (inter- A particular form of mucinous
capillary glomerulosclerosis) in mesan- dystrophy occurs in mucoviscidosis – a

gium can be seen in the renal glomeruli. hereditary disease, characterized by a
The process may be reversible. change of the mucus secreted by the
Parenchymatous mucinous dystro mucosecreting epithelium of mucosas
phy is characterized by exaggerated and exocrine glands. The mucus beco-
secretion and accumulation of mucus mes viscous, dense, it is eliminated with
(mucin) in the cytoplasm of the mu- difficulty, leading to retention of eva-
cosecretory cells, as well as change of cuation of secretions and formation of
physicochemical properties of the mu- mucus “plugs”. Inflammatory processes,
cus. It can be seen in the mucosas of the cystic dilatation and deformation of
bronchi, digestive tract, uterus and in excretory ducts, sclerosis, atrophic pro-
glandular organs (pancreas, sudoripa- cesses of glandular parenchyma become
rous, lacrimal and mammary glands) in associated. Most frequently, the exocri-
cases of chronic inflammations (chronic ne pancreas is affected (the fibro–cystic
bronchitis, bronchial asthma, muciparo- disease of the pancreas), but also the
us cancer, especially in signet ring cell bronchi, salivary glands, sudoriparous
cancer (Fig. 2–11), mucoviscidosis (he- and lacrimal glands, the small intestine,
reditary enzymopathy). genitourinary organs. The development,
Macroscopically, the harmed organs clinical manifestations and complica-
(tissues) show an excess of mucus, an tions of mucoviscidosis depend on the
obstruction of glandular ducts and of preponderant localization of lesions.

2 . 4 . E X T R AC E L LU L A R D Y S T R O P H I E S
( M E S E N C H Y M A L O R S T R O M A L - VA S C U L A R )
In extracellular or mesenchymal tively, in interellular substance of stroma

(stromal-vascular) dystrophies, the me- of the organs and of vascular walls. The
tabolic disturbances take place in ground morphogenetic mechanisms of mesen-
substance and fibrillar elements of the chymal dystrophies are: infiltration, de-
connective tissue, particularly in stroma composition, transformation and patho-
of organs and in walls of vessels (the ba- logical synthesis.
sement membrane of blood vessels con- According to the type of altered me-
sists of ground substance and reticulinic tabolism, the mesenchymal dystrophies
fibers). They are manifested by deposi- is divided into proteic, lipidic and gluci-
tion of some metabolic products, which dic dystrophies (Table 2.3).
are changed quantitatively and qualita-
Table 2.3
Classification of extracellular dystrophies
a) mucoid intumescence;
b) fibrinoid intumescence;
I. Proteic
c) hyalinosis;
d) amyloidosis.
I – neutral fats metabolism disturbances:
a) generalized:
1) – obesity;
2) – cachexia;
b) localized:
II. Lipidic 1) segmental lipomatoses (adiposities);
2) regional lipodystrophy;
II – disturbances of cholesterol and its esters metabolism (in
atherosclerosis of arteries and familial hypercholesterolemic
xanthomatosis);
a) – mesenchymal mucous dystrophy (myxomatosis of tissues);

III. Glucidic
b) – mucopolysaccharidoses (Hurler disease or gargoilysm)
2.4.1. PROTEIC EXTRACELLULAR DYSTROPHIES

(EXTRACELLULAR DISPROTEINOSES)
The following varieties of extracellu- and amyloidosis. The first three can be
lar disproteinoses can be distinguished: consecutive phases of the one and the
mucoid intumescence, fibrinoid intu- same process of disorganization of con-
mescence (degenerescence), hyalinosis nective tissue (ex: in rheumatic diseases).

2.4.1.1. MUCOID INTUMESCENCE
The mucoid intumescence repre- The macroscopic aspect of the organs
sents a superficial and reversible disor- is unchanged, the lesions can be revealed
ganization of connective tissue, charac- only at a microscopic examination with
terized, from biochemical point of view, histochemical reactions to highlight the
by accumulation and redistribution of glycosaminoglycans. When stained with
glycosaminoglycans (especially of hya- toluidine blue, the dystrophic foci are
luronic acid) in ground substance. Hy- colored metachromatically in purple or
drophilia of glycosaminoglycans indu- red, like mucins, on a blue (orthochro-
ces a significant increase of vasotissular matic) background of intact connective
permeability, which leads to infiltrati- tissue (hence the name “mucoid intumes-
on of ground substance with plasmatic cence”) (Fig. 2–12b).
proteins (albumins and gammaglobu- Mucoid intumescence is present in
lins), hydration and intumescence of different organs and tissues, but mostly
interstitial tissue. Collagenic fiber fas- in the walls of arteries, the heart valves
cicles are tumefied; interfibrillar spaces and parietal endocardium in hypoxia, in
are considerably enlarged, as a result various infectious, allergic, rheumatic di-
of hyperhydration, and contain micro- seases, atherosclerosis, etc.
granular proteic masses. The collagenic It is a reversible process, but it can
fibers keep their normal structure and develop into fibrinoid degenerescence, if
transversal striation, being only tume- the causative factor is not removed. The
fied (mucoid, chromotrope or myxoma- function of organs in mucoid intumes-
tous edema) (Fig. 2–12a). cence is slightly impaired.
CF 2 3  G E N E R A L M O R P H O P A T O L O G Y IEREMIA ZOTA, VLADIMIR VATAMAN
a b
Fig. 2–12 a, b. Mucoid intumescence of the connective tissue: a – electron microscopic image
(×35000); CF – collagenic fibers; b – microscopic pattern (stain with toluidine blue ×110).
2.4.1.2. FIBRINOID INTUMESCENCE
This is an irreversible process of di- formation. The fibrinoid is a complex

sorganization of the connective tissue. substance, consisting of proteins and
It is characterized by the distruction polysaccharides resulted from colla-
of the ground substance and of collagenic fibers and ground substance de-
gen fibers, by a considerable increase of gradation, as well as from plasmatic
vasotissular permeability and fibrinoid proteins, extravasated as a result of an

increased permeability of vessels. The A macrophage and lymphocytic in-

main component of fibrinoid is the fi- filtration can be seen around the foci of
brin (Fig. 2–13). Consequently, the fi- necrosis. As a result, sclerosis (cicatriza-
brinoid has tinctorial properties similar tion) and hyalinosis processes appear on
with the fibrin, from which the name the territories of fibrinoid changes, with
derives. No characteristic changes are important functional alterations of the
noted macroscopically. The function of given organ.
It can be seen in some allergic, au-
the organs is severely impaired.
toimmune, angioneurotic, dysmetabo-
We distinguish the fibrinoid dege-
lic, infectious diseases, etc. (rheumatic
nerescence of connective tissue and of diseases, glomerulonephritis, arterial
blood vessels. When progressing, the fi- hypertension, atherosclerosis). Fibrinoid
brinoid changes lead to fibrinoid necro- necrotic foci of connective tissue with
sis of the connective tissue, which turns cellular cord constitute the morpholo-
into a homogeneous mass with eosi- gical substrate of rheumatic granulomas
nophilic tinctoriality (Fig. 2–14). (Aschoff granulomas).
CF
F
Fig. 2–13. Fibrinoid intumescence of connecti- Fig. 2–14. Fibrinoid necrosis of connective tis-
ve tissue (electron microscopy; ×35000): CF – sue in rheumatism (hematoxylin–eosin stain;
collagenic fibers; F – fibrin. ×110).
2.4.1.3. EXTRACELLULAR HYALINOSIS (HYALINE DYSTROPHY)
It is characterized by the appearance connective tissue and the increase of va-
of hyaline in tissues – a semitransparent sotissular permeability (plasmorrhagia).
whitish mass of hard consistency, with a Hyalinosis may develop as a result of:
glassy aspect, similar to hyaline cartilage a) fibrinoid intumescence, b) plasmatic
and deposited extracellularly. Hyaline imbibition (plasmorrhagia), c) chronic
is a substance of proteic origin (fibrillar inflammation; d) necrosis; e) sclerosis.
protein), which, microscopically, ap- We distinguish hyalinosis of con-
pears unstructured, homogeneous, eo- nective tissue and hyalinosis of blood
sinophylic; it is resistant to the action vessels.
of enzymes, acids and bases. The main Hyalinosis of vessels appears
mechanism of hyalinosis production is mostly in small arteries and arterioles,
the destruction of fibrillar structures of preceded by the increase of vascular

permeability and plasmatic imbibiti- These alterations lead to ischemia and
on (plasmorrhagia) of the vessel walls. hypoxia of the organ, atrophy of paren-
Vascular hyaline is formed from plas- chyma and perivascular proliferation of
matic precursors, especially from blood connective tissue.
plasma proteins, accumulating initially These lesions are characteristic par-
in the subendothelial space. The smo- ticularly for arterial hypertension and
oth muscle cells and fibrillar elements diabetes mellitus. First to be affected
of vascular walls become atrophied are the small arteries of the brain, heart,
gradually and imbued with fibrin and kidneys, retina, endocrine glands etc. In
other plasmatic components. Later, the such cases, the process of arterial hyali-
affected vessel turns into a hyaline tube nosis has a generalized character.
(becomes similar with a glass tube) with Local hyalinosis of arteries can be
a thickened wall and a very narrow or noted in the spleen, representing a phy-
completely closed up lumen (Fig. 2–15). siological process, determined by the

a b
Fig. 2-15. Hyalinosis of lienal arteries (a) and of renal arterioles (b); hematoxylin–eosin
stain ×110.
morphofunctional specific features of

the spleen, as a blood storage organ.
First of all, the hyalinosis of the
connective tissue can be seen in rhe-
umatic diseases, preceded by fibrinoid
intumescence of connective tissue. In
these cases, the hyaline is formed from
fibrinoid masses. A characteristic exam-
ple may be the sclerosis and hyalinosis
of the heart valves in rheumatism and
other rheumatic diseases, leading to
their thickening and deformation, and
forming of cardiac valvulopathies (Fig.
Fig. 2–16. Hyalinosis of mitral valve (rheumatic 2– 16). The hyalinosis of the connective
valvulopathy).

tissue in these diseases has a generalized rences, in the spleen capsule in ascites
character. (“icing-sugar” or „sugar-coated” spleen)
Local hyalinosis is noted in gastric (Fig. 2– 18).
ulcer, keloid scars (Fig. 2–17), adhe- Hyalinosis is usually an irreversible
Fig. 2-17. Hyalinosis of connective tissue (he- Fig. 2-18. Hyalinosis of spleen capsule.
matoxylin–eosin stain; ×110). phrosclerosis with wrinkling of kidneys
process, which may end in functional in arterial hypertension, rheumatismal
disturbances and severe complicati- cardiac valvulopathies, diabetic glome-
ons (for example, arteriolosclerotic ne- rulosclerosis and retinopathy etc.)
2.4.2. LIPIDIC EXTRACELLULAR DYSTROPHIES
Metabolic disturbances of neutral lobe of pituitary gland or hormonal
fats are located at the level of adipose active tumors of corticoadrenals);
tissue. An excessive growth (obesity) or  in hypothyroidism – diminishing
decrease (cachexia) of fatty deposits may of the function of the thyroid gland
occur. (myxedema);
Obesity may be primary, determined  in hypogonadism – hyposecreti-

by constitutional–hereditary factors (the on of androgenic hormones (in-
need of nourishment with an increased flammatory processes, tumors of
caloric value is determined genetically), testicles, in cases of castration, in
and secondary, which is symptomatic and climacterium;
is observed in some cerebral, endocrine  in hyperinsulinism – insulin hyper-
and hereditary diseases. The following secretion (adenoma from beta cells
variants of secondary obesity can be ob- of pancreatic islets).
served, from this point of view: d) hereditary – caused by genetic de-
a) food obesity – caused by an excessive fects (including hereditary enzymo-
nutrition and hypodynamia (seden- pathies).
tary lifestyle); From the morphological point of
b) cerebral – in various cerebral tumors, view, obesity manifests itself by growth
traumatisms, neurotropic infections; of deposition of fats in subcutaneous
c) endocrine – in various pathologic tissue, epiploon, mediastinum, mesen-
processes of endocrine glands, for tery, retroperitoneal tissue, the bed and
example, stroma of some internal organs (heart,
 in hypercorticism – hypersecreti- pancreas, kidneys, and liver). In primary
on of the corticosteroid hormones obesity, a hypertrophy of fat cells occurs,
(basophilic adenoma of the anterior leading to their diminished sensitivity to

insulin. In all the forms of obesity, the achieve 1–2 cm (the normal one sho-
heart lipomatosis occurs. The fat cells uld be 2–3 mm). The contractile power
infiltrate the myocardium, dissociating of the heart drops, developing a cardiac
the muscular fiber bands, which later on insufficiency; even a rupture of the right
become atrophied (Fig. 2–19 a). Macro- ventricle wall may occur, with a tam-
scopically, the heart becomes enlarged ponade of pericardial sac and sudden
in size, abundant deposits of fat appear death. It should be mentioned that obe-
under the epicardium, surrounding the sity (including the heart lipomatosis) is
heart like a muff (Fig. 2–19 b). These one of the risk factors of ischemic heart
manifestations are more profound in disease (ischemic cardiopathy).
the right ventricle, whose thickness may The local increase of the adipose tis-
a b
Fig. 2–19 a, b. Heart lipomatosis: a – microscopic pattern (hematoxylin–eosin stain; ×70); b – ma-
croscopic aspect.
sue content takes place in lipomatosis, neous tissue of the extremities and of
for example in the Dercum disease. It is the trunk, sometimes painful (lipomato-
characterized by the appearance of some sis dolorosa), reminding lipomas. This is

nodules, formed of fats, in the subcuta- endocrine polyglandular pathology.
2.4.3. GLUCIDIC EXTRACELLULAR DYSTROPHIES
Mesenchymal mucous dystrophy tissue of the fetus and umbilical cord. It

(myxomatosis of tissues). This variant can be observed in connective tissue in
of extracellular dystrophy presents dis- myxedema and cachexies, in cardiac val-
turbances of glycoproteins metabolism ves in Marfan syndrome etc. The phe-
from ground substance of connective nomenon of myxomatosis is frequently
tissue. The main glycoproteins are the observed in tumors of connective, car-
mucoids, secreted by the cells of the tilaginous and osseous tissues. It is very
connective tissue (fibroblasts, chondro- characteristic for myxomas. The cells of
blasts and osteoblasts), an important the connective tissue acquire a stellate
component of ground substance. In shape. The myxomatosis can develop in
case of metabolic disorders, the mucoids some tumors as a manifestation of se-
accumulate excessively in the connective condary lesions. The processes of myxo-
tissue and the collagenic fibers are sub- matosis may result in tissue necrosis and
stituted with a mucoid mass. The con- formation of some cystic cavities, filled
nective tissue gets a myxomatous, gela- with mucus.
tinous aspect, similar with the myxoid

2.5. ACCUMULATION DISEASES

(THESAURISMOSES OR STORAGE DISEASES)
This is a group of diseases charac- amniocentesis, justifying the importance

terized by insufficiency or absence of of a genetic consultation before giving
enzymes in the body, which leads to birth.
accumulation of some intermediate sub- The thesaurismoses can be grouped
stances in the organs and tissues, which conventionally into:
cannot be metabolized. They are heredi-  congenital disorders of amino acids
tary diseases based on defects of genes, metabolism,
which codify certain enzymes (heredi-  lysosomal diseases of accumulation
tary, congenital enzymopathies). These (lysosomal storage diseases).
diseases can be diagnosed antenatally by
2.5.1. HEREDITARY DISORDERS OF AMINO ACIDS METABOLISM
The main diseases of this group are by hereditary insufficiency of phenyla-

cystinosis, tyrosinosis, phenylketonuria lanine–hydroxylase enzyme, leading to
and alkaptonuria. hyperphenylalaninemia and phenylket-
Cystinosis is determined by altera- onuria. The excess of phenylalanine and
tion of metabolism of cystine, as a result its derivatives impairs the development
of a congenital enzymatic deficiency. It of the brain by the inhibition of amino
is characterized by deposition of cysti- acids supply, synthesis of neuromedia-
ne crystals in the kidneys, liver, spleen, tors and myelin, causing a state of men-
cornea, bone marrow and other tissues. tal retardation of the child (dementia or
Clinically, it is manifested by the distur- phenylpyruvic oligophrenia).
bance of kidney function (urinary calcu- Alkaptonuria is characterized by
losis), physical development delay, and metabolic disturbance of phenylalanine

changes of the skeleton, similar with and accumulation of homogentisic acid
rickets (vitamin resistant rickets). in connective tissue of all organs, as a
Tyrosinosis is a manifestation of ty- result of insufficiency of homogentisic
rosine metabolic disturbance, caused by acid oxidase enzyme. Clinically, it is ma-
tyrosine aminotransferase deficiency. Cli- nifested by dystrophic lesions of joints,
nically, it is manifested by hypertyrosine- determined by the storage of homogen-
mia, liver, kidneys and bones impairment. tisic acid in joints cartilages and inter-
Phenylketonuria is a disturbance of vertebral discs.
phenylalanine metabolism, conditioned
2.5.2. THE LYSOSOMAL ACCUMULATION DISEASES

(LYSOSOMAL STORAGE DISEASES)
They represent a group of hereditary of lysosomal acidic hydrolases. Accor-

diseases, characterised by accumulation ding to the nature of disturbed metabo-
in lysosomes of some intermediate, non- lism, we distinguish: systemic lipidoses,
metabolized substances. They are cau- glycogenoses and mucopolysacchari-
sed by lack or congenital insufficiency doses.

2.5.2.1. SYSTEMIC LIPIDOSES OR LIPID STORAGE DISEASES
According to the type of lipids accu- rons and macrophages. Clinically, it is
mulated in cells, they are subdivided in manifested by psychic disturbances and
the Gaucher, Tay–Sachs and Niemann– amaurosis (blindness), hence the name
Pick diseases. of amaurotic idiocy. A deficiency of he-
The Gaucher disease or cerebroside xosaminidase enzyme is registered bio-
lipidosis is caused by the lack of glucoce- chemically.
rebrosidase enzyme and is characterized The Niemann–Pick disease or
by an accumulation of glucocerebrosides sphingomyelin lipidosis is manifested
in the reticuloendothelial cells, with the by accumulation of sphingomyelin in
appearance of the so-called Gaucher parenchymatous and reticuloendothelial
cells - macrophages filled with lipids. cells. The biochemical mechanism con-
Clinically, it manifests itself by hepatos- sists in the deficiency of sphingomyeli-
plenomegaly and bone lesions. nase enzyme, which divides the sphyn-
The Tay–Sachs disease or gangli- gomyelin. Clinically, there are neurologic
oside lipidosis is an accumulation of signs, jaundice, and hepatosplenomegaly.
gangliosides in the lysosomes of neu-
2.5.2.2. GLYCOGENOSES OR GLYCOGEN STORAGE DISEASES
They are manifested by accumula- ency. Clinically, a massive cardiomegaly
tion of glycogen in tissues and organs and a severe cardiac insufficiency are re-
with normal or deteriorated structure. gistered.
The Gierke disease is characterized The McArdle disease is caused by
by excessive accumulation of glycogen insufficiency of muscle phosphorylase
in parenchymatous organs, particularly and manifests itself by accumulation of
in the liver and kidneys. It is caused by glycogen in myocytes, and clinically - by
the deficiency of glucose–6–phospha- myopathy.
tase enzyme. Clinically, a hepato- and The Forbes–Cori disease is based

renomegaly is registered, and, microsco- on the hereditary deficiency of amy-
pically - massive deposits of glycogen in lo–1,6–glucosidase, resulting in accu-
the liver, kidneys, muscles, the mucosa mulation of glycogen, with abnormal
of the digestive tract and the nervous structure in the liver, muscles and heart.
system. Besides generalized glycogenoses,
The Pompe disease is an excessive there are localized accumulations of
accumulation of glycogen in myocar- glycogen, for example, in some tumors,
dium, smooth and skeletal muscles. It is like seminoma and clear cells renal car-
caused by the alpha-glucosidase defici- cinoma.
2.5.2.3. MUCOPOLYSACCHARIDOSES
The mucopolysaccharidoses are cha- organs and blood vessels and, clinically,
racterized by tissular accumulation of by distortion of the face, low height,
glycosaminglycans (mucopolysacchari- osseous and articulation lesions, hepa-
des) and their elimination via urine in in- tosplenomegaly, mental retardation. Mi-
creased amount. The Hurler syndrome croscopically, one reveals mucopolysa-
is most frequently observed, being caused ccharide deposits in phagocytic cells,
by the hereditary deficiency of the alpha fibroblasts, endotheliocytes and smooth
–iduronidase enzyme. It is manifested by muscle cells of vascular walls. The clini-
accumulation of heparan sulphate and cal syndrome is called gargoylism (from
dermatan sulphate in parenchymatous the Latin gargulio – throat).

ESSENTIAL TERMS
on the subject “Reversible cellular and extracellular lesions”
accumulation disease hyalinosis obesity

alcoholic hyaline hydropic dystrophy orthochromasia
alkaptonuria hyperkeratosis pathologic synthesis
alteration ichthyosis phanerosis
cellular hyaline „icing-sugar” spleen phenylketonuria
dystrophy
cloudy intumescence infiltration plasmatic infiltration
cystinosis lesion Pompe disease
decomposition leukoplakia Russel corpuscles
dystrophy lipomatosis steatosis
fibrinoid intumescence Mallory corpuscles storage disease
Forbes–Cori disease McArdle disease „sugar-coated” spleen
gargoylism metachromasia Tay-Sachs disease
Gaucher disease mucoid intumescence thesaurismosis
Gierke disease mucopolysaccharidosis tiger heart
glycogenosis mucoviscidosis transformation
granular dystrophy myxomatosis tyrosinosis
Hurler disease Niemann–Pick disease vacuolar dystrophy
TESTS
on the subject “REVERSIBLE EXTRACELLULAR AND CELLULAR LESIONS”

SET I
Multiple-choice questions with one cor- e) pathological keratinization of the

rect answer mucous membranes.
1. Which of the signs listed below characteri- 3. Which of the listed terms indicate the accu-
ze the granular dystrophy: mulation of lipids in parenchymatous cells:
a) large, homogeneous, hyaline dro- a) lipomatosis;
plets in cells cytoplasm; b) steatosis;
b) formation of vacuoles in cytoplasm c) systemic lipoidosis;
and nucleus; d) sphyngolipidosis;
c) small eosinophilic granulations in e) lipofuscinosis.
the cells cytoplasm; 4. Which is the main cause of myocardial ste-
d) pathologic keratinization; atosis:
e) granules of glycogen in cytoplasm. a) hypoproteinemia;
2. Definition of leukoplakia: b) hypoxia;
a) excessive keratinization of the skin; c) hypocalcemia;
b) vacuolar dystrophy of the skin; d) hypoglycemia;
c) parakeratosis; e) hyperuricemia.
d) formation of keratin pearls;

5. Which of the listed processes characterize the connective tissue;
mucoid intumescence: c) accumulation of lipids;
a) develops in the cells of connective d) accumulation of glycogen;
tissue; e) accumulation of proteins.
b) develops in ground substance of
SET II.
Multiple-choice questions with 2, 3 or g) dense consistency of myocardium.
more correct answers 3. Which of the listed dystrophies are characte-
1. Macroscopic changes of organs, characteristic for rheumatism:
ristic for granular dystrophy: a) cloudy intumescence;
a) enlarged in size; b) mucoid intumescence;
b) diminished in size; c) glycogenosis of cardiac valves;
c) flaccid consistency of the organ; d) fibrinoid intumescence;
d) cloudy aspect on the section; e) intracellular hyalinosis;
e) densification of the organ; f ) extracellular hyalinosis.
f ) the organ maintains its usual luster. 4. Which of the listed lesions of arteries occur
2. Which of the signs listed below are charac- in arterial hypertension:
teristic for the “tiger heart”: a) amyloidosis of arteries;
a) enlarged size; b) hyalinosis of small caliber arteries;
b) dilated cavities; c) lipidic infiltration of arteries;
c) subepicardial adipose tissue deposits; d) plasmatic infiltration of arteries;
d) brown color of the myocardium on e) glycogenic infiltration of arteries.
the section; 5. Which of the listed signs are characteristic
e) white–yellowish stripes under the for fibrinoid intumescence:
endocardium of the papillary mus- a) considerable increasing of vascular
cles;

permeability;
f ) adipose tissue in the stroma of myo- b) it is a reversible process;
cardium;
SET III.
Classification tests include 2–4 subjects d) destruction of cytoplasmic organel-

and a series of answers. Indicate the correct les.
answers for each subject separately. 2. Which of the morphological changes are
c) collagenic fibers destruction; characteristic for:
d) positive reaction to fibrin; I – hydropic dystrophy of myocardium;
e) formation of fibrinoid. II – fatty dystrophy of myocardium;
1. Which of the morphologic signs listed below a) yellowish stripes under the endocar-
are characteristic for: dium;
I – cellular hyaline dystrophy; b) presence of some vacuoles in sarco-
II – granular dystrophy; plasma, filled with cytoplasmic fluid;
a) large proteic droplets, confluent in c) presence of some droplets in sarco-
the cell cytoplasm; plasma, stained with Sudan III;
b) tumefaction of mitochondria; d) the myocardium is not changed ma-
c) fine proteic granules in cytoplasm; croscopically;

e) dilatation of endoplasmic reticulum e) stripped aspect of myocardium on

cisterns. section;
3. In which of the listed diseases one notices: f ) the cardiomyocytes are enlarged in
I – the liver steatosis; size;
II – hydropic dystrophy of the liver; g) it is the morphological substrate of
a) thyrotoxic goiter; the contractile activity decompen-
b) excess of fats in food; sation of the heart.
c) ethanol intoxication; 5. Which of the listed signs are characteristic
d) avitaminoses; for:
e) chronic pulmonary pathology; I – mucoid intumescence;
f ) viral hepatitis. II – fibrinoid intumescence;
4. Which of the listed signs are characteristic for: a) it is a reversible process;
I – liver steatosis; b) the destruction of collagenic fibers
II – myocardial lipomatosis; occurs;
a) lipidic vacuoles in cytoplasm of car- c) it is an irreversible process;
diomyocytes; d) the fascicular structure of collagenic
b) it is most frequently noted in obe- fibers is maintained;
sity; e) it is revealed when stained with to-
c) accumulation of adipocytes among luidine blue;
myocardial fibers; f ) hyaluronic acid accumulation
d) deposits of fats under epicardium; occurs.
SET IV. SITUATIONAL PROBLEMS
Daily practice cases are presented with b) decomposition;
clinical and morphological data from clini- c) transformation;
cal histories and/or from necropsy protocols. d) denatured synthesis.
Each subject includes simple or multiple- 2. An 18 year-old patient had throat pains
answer questions, with 1, 2 or more correct and a fever up to 39 °C, enlarged cervi-
answers. cal lymph nodes, membranes of white–
1. A patient with pandemic influenza grayish color on mucosa of the palatine
had tachycardia and traces of proteins tonsils, which detach with difficulty,
in urine. The activity of the heart and leaving bleeding ulcerations. A diagno-
the characteristics of the urine became sis of diphtheria was made. In 8 days,
normal after treatment. the patient died because of acute heart
Questions: failure. During the necropsy, the myo-
cardium had a very flaccid consistency
A) Which dystrophic process took place in
and a claylike aspect on the section; the
the myocardium and kidneys:
heart cavities were considerably dilated.
a) fatty dystrophy;
b) hydropic dystrophy; Question:
c) granular dystrophy; Which pathological changes can be revea-
d) glucidic dystrophy; led in cardiomyocytes:
e) amyloidosis; a) glucidic dystrophy;
f ) cellular hyalinosis. b) vacuolar dystrophy;
B) Which morphogenetic mechanism of c) fatty dystrophy;
dystrophy prevails in myocardium (1) d) intracellular hyaline dystrophy;
and kidneys (2): e) granular dystrophy.
a) infiltration;

3. A patient died because of chronic al- Question:
coholic intoxication and, at necropsy Which are the substances that reflect this
of the corpse, the following macro- microscopic pattern, when accumulated:
scopic changes of the liver were re- a) glycogen;
vealed: increased mass up to 4,5 kg b) lipoproteins;
(the average norm being 1,5– 1,6 kg), c) hyaline;
flaccid consistency and yellow color. d) amyloid;
Questions: e) glycosaminoglycanes;
A) Which histological changes can be f ) neutral fats.
revealed in the liver biopsy: 5. A 45 year-old patient died suddenly
a) accumulation of glycogen in hepa- because of a heart attack. The necrop-
tocytes; sy revealed grade III obesity, universal
b) presence of fat droplets in hepato- type, rupture of the right ventricle wall
cytes; with pericardial tamponade (more than
c) proliferation of fatty (adipose) tis- 350 ml of bloody fluid and clots in the
sue through hepatic trabeculae; pericardial sac), the heart in systole sta-
d) accumulation of amyloid in the lite, abundant deposits of adipose tissue
ver. under the epicardium, the thickness
B) Which method of staining should be of the right ventricle wall - 1,8 cm.
applied to make a correct diagnosis: The histological examination revealed
a) hematoxylin and eosin; agglomerations of adipocytes, infiltra-
b) Sudan III; ting the stroma of the myocardium, the
c) carmine; muscular fibers being atrophied.
d) Congo red. Question:
4. A focus of tumefaction of collagenic Which pathological process of those listed
fibers was revealed during the mi- occurs in the given case?
croscopic examination of the biopsy a) myocardial steatosis;
from the capsule of the knee joint of

b) arterial hypertension;
a patient with rheumatoid arthritis. c) ischemic cardiomyopathy;
It was stained in red with toluidine d) acute myocardial infarction;
blue. e) heart lipomatosis.
2.6. REVERSIBLE MIXED INTRA - AND EXTRACELLULAR LESIONS

(MIXED DYSTROPHIES)
In cases of mixed lesions (dystrophi- proteins, lipoproteins, glycoproteins)

es), metabolic disturbances take place and of mineral substances. It is manifes-
both in the parenchyma of organs and ted through quantitative and qualitative
tissues (intracellular) and in the stromal changes of respective substances in the
connective tissues (extracellular). Usu- cells and intercellular compartment.
ally, it is alteration of mixed proteins
metabolism (chromoproteins, nucleo-

2.6.1. CHROMOPROTEINS DYSTROPHIES
The chromoproteins or pigments of ke the exogenous pigments, which enter the

endogenous origin are colored complex body from the external environment. They
proteins synthesized in the organism, unli- are classified in three groups (Table 2.4).
Table 2.4
Classification of endogenous pigments dystrophies
Groups of pigments The pigments
Physiological hemoglobinogenic pigments
a) ferritin
b) hemosiderin
c) bilirubin
Pathological hemoglobinogenic pigments
Hemoglobinogenic pigments a) hematoidin
b) hematins
Ø hemomelanin
Ø hydrochloric hematin
Ø formalin pigment
c) porphyrin
Proteinogenic pigments melanin
a) lipofuscin
Lipidogenic pigments
b) lipochromes
Morphologically, metabolic distur- in pathologic conditions. The pigment

bances of chromoproteins can manifest metabolism can be disturbed secondarily

themselves by increasing or diminishing in many diseases and pathological pro-
the quantity of pigments present in the or- cesses. In other cases, these disturbances
ganism normally or by the appearance and develop primarily, representing morpho-
deposition of some pigments, formed only logical substrate of some diseases itself.
2.6.1.1. HEMOGLOBINOGENIC PIGMENTS DYSTROPHIES
These pigments are formed as a re- iron. It is formed intracellularly in re-

sult of hemolysis of erythrocytes and ticuloendothelial (sideroblasts) cells. It
degradation of hemoglobin, having the appears in the first 24 hours, in cases of
following specific features: hemorrhages. The level is increased in
a) Ferritin – ferroprotein, the main generalized and localized hemosiderosis
iron storage in the body. It is formed and hemochromatosis. The Pearls reac-
in the organs of the reticuloendotheli- tion is used to identify the hemosiderin
al system (liver, spleen, bone marrow, in histological samples: blue granules of
lymph nodes). The level is increased in ferrous ferricyanide are formed (also cal-
hemosideroses. led Berlin or Prussian blue) on treating
b) Hemosiderin – an amorpho- microscopic sections with potassium
us pigment of brown color, containing ferrocyanide and hydrochloric acid.

c) Bilirubin – a crystalline pigment mulated extracellularly in areas of limi-
of yellow color that doesn’t contain iron. ted oxygen supply, remoted from viable
The indirect (free, unconjugated) biliru- tissues, mostly in necrotic masses. In
bin is formed in reticuloendothelial cells, hemorrhagic foci, it is formed in 5–10
being eliminated later in blood plasma. days after the hemosiderin. It is revealed
The direct (conjugated) bilirubin is for- in old hematomas, hemorrhagic infarc-
med in hepatocytes, by conjugation of tions, hemangiomas - in their central
free bilirubin with glucuronic acid, and areas, situating themselves freely in ne-
is excreted in the bile. The level is incre- crotic masses. The hemosiderin can be
ased in jaundice syndromes. revealed in large hemorrhagic foci, at the
d) Hematoidin – a crystalline pig- periphery, while the hematoidin - in the
ment of orange color that doesn’t conta- centre. The Pearls reaction indicates the
in iron. It is identical to bilirubin and it lack of iron in hematoidin (Fig. 2–20).
is also called tissular bilirubin. It is accu-
a a
b
b
c
1 2

Fig. 2–20. Old cerebral hemorrhage (old cerebral hematoma) (hematoxylin – eosin stain (1) and
Pearls reaction (2); ×70): a – hemosiderin; b – hematoidin; c – necrotic focus.
e) The hematins: ons and gastric ulcers, staining them in

1) hemomelanin or malarial pig- black (Fig. 2–21).
ment – a crystalline pigment of brown-
black color that contains iron. It is formed
in erythrocytes, under the action of ma-
laria plasmodia. The level is increased in
patients with malaria (hemomelanosis).
It penetrates the blood after the destruc-
tion of erythrocytes and is phagocyted by
circulating and tissular macrophages.
2) hydrochloric hematin – a
crystalline pigment of brown-black co-
lor that contains iron. It is formed under
the influence of the digestive enzymes
and of the hydrochloric acid from gastric Fig. 2–21. Hydrochloric hematin on the bottom
juice. It gathers on the bottom of erosi- of gastric mucosal erosions.

3) formalin pigment – a brown– bed deposition of hemosiderin in di-

black pigment, formed in tissues fixed in fferent organs and tissues, which gives
acid formalin. them a brown color (Fig. 2–24). At the
f ) the porphyrin does not contain microscope, granules of hemosiderin can
iron and has a red luminescence in ultra- be revealed in the cytoplasm of mesen-
violet rays; it is revealed in small quan- chymal and epithelial cells. Initially, the
tities in blood, urine, tissues; it increases
the sensitivity of the skin to light, the
level is high in porphyria, which can be
congenital or acquired.
The hemoglobinogenic pigments
dystrophies can manifest themselves
by the increased quantity of pigments
formed in physiological conditions (fer-
ritin, hemosiderin and bilirubin) or by
the appearance of some pigments that
appear only in pathological conditions
(hematoidin, hematin and porphyrin).
The most common dystrophies of the Fig. 2–22. Hemosiderosis of the kidney (hema-
hemoglobinogenic pigments are: hemo- toxylin–eosin stain; ×70).
siderosis, hemochromatosis, jaundice,
hemomelanosis and porphyria.
Hemosiderosis can be generalized
and localized:
Generalized hemosiderosis is cau-
sed by intravascular hemolysis of eryth-
rocytes; it occurs in hemolytic anemias,
leukemias, severe infectious diseases

(septicemias), intoxications (for exam-
ple, with snake venom), and incompatible
blood transfusions. The storage of he-
mosiderin takes place in the cells of the
reticuloendothelial system and of pa- Fig. 2–23. Hemosiderosis of the liver (hemato-
renchymatous organs. Concomitantly, xylin–eosin stain; ×110).
an increase of ferritin and bilirubin
synthesis is noticed. The affected or-
gans (spleen, liver, bone marrow, lymph
nodes and kidneys) have a rust color.
Granules of hemosiderin can be revea-
led microscopically in the cytoplasm of
cells (Fig. 2–22 and 2–23).
Localized hemosiderosis is caused
by extravascular hemolysis of erythro-
cytes. It occurs in hemorrhages, hemor-
rhagic infarctions, chronic venous stasis
of the organs and tissues. Morphologi-
cally, is noticed a localized, circumscri- Fig. 2–24. Cerebral hematoma.

subcutaneous suggillations have a blue a) Hemolytic jaundice (prehepa-
violet (purple) color, but, within 7–10 tic) is related to excessive hemolysis of
days, they get a yellow – greenish shade, erythrocytes. It can be observed in he-
as a result of consecutive formation of molytic anemias, leukemias, intoxica-
various hemoglobin pigments: hemosi- tions, infectious diseases, incompatible
derin (brown), hematoidin (yellow) and blood transfusions. The level of the free
biliverdin (greenish). (indirect, unconjugated) bilirubin is in-
Hemochromatosis can be primary creased in blood plasma. At an exterior
and secondary: examination, is noticed the yellow colo-
a) Primary hemochromatosis is a ration of all organs and tissues, especi-
thesaurismosis with a familial character, ally of the teguments, mucosas, scleras
caused by a congenital defect of enzymes, and serosas.
which regulates the use (metabolism) b) Hepatic jaundice (parenchyma-
of iron in the organism. An excessive tous) is caused by destructive lesions of
absorption of the exogenic iron (ali- hepatocytes in hepatitides, hepatoses,
mentary) occurs in the duodenum. The and hepatic cirrhoses. An increase of the
content of iron in the body rises dozens free and conjugated bilirubin in blood
of times. Morphologically, is noticed a plasma is noticed.
deposition of hemosiderin and ferritin c) Mechanical jaundice (subhepatic,
in organs and tissues and of melanin - obstructive) is related to the impairment
in the skin. The affected organs have a of bile ducts permeability (bile stasis)
dark brown color and a hard consistency. (Fig. 2–25). It can be seen in cases of bile
At the microscope, is observed granu-
les of hemosiderin in the cytoplasm of
the cells and an excessive proliferation
of connective tissue. The liver, pancreas,
skin, heart, endocrine glands, and gastric

mucosa become affected. The cardinal
signs are: pigment hepatic cirrhosis, di-
abetes mellitus, brown (bronze) color of
the skin and cardiomyopathy. The disea-
se is also called bronze diabetes because of
the hyperpigmentation of the skin.
b) Secondary hemochromatosis is Fig. 2–25. The liver with bile stasis in mecha-
conditioned by insufficient use of iron in nical jaundice (hematoxylin–eosin stain; ×70).
the processes of hematopoiesis. It can be ducts occlusion by gallstones, tumors of
noticed in massive hemolysis of eryth- bile ducts, parasites, malformations or
rocytes, excessive intake of alimentary by external compression (metastases of
iron, repeated blood transfusions and cancer in lymph nodes of the hepatic hi-
hemoglobinopathies. Morphologically, lum, tumors of the head of the pancre-
a deposition of hemosiderin and ferritin as, tumors of duodenal papilla/ampulla
is revealed in organs and tissues (liver, of Vater, adherences). From the clinical
pancreas, myocardium etc). The affected point of view, there is an excess of direct
organs have a dark–brown color and an (conjugated) bilirubin in the blood, whi-
increased consistency. ch determines a yellow–green pigmen-
Jaundice may be hemolytic, paren- tation of tissues, including the skin and
chymatous and mechanical. sclerae. Besides the intensive coloration

of teguments in obstructive jaundice, is

noticed a general intoxication induced
by bile acids, hemorrhagic syndrome,
dystrophic lesions of kidneys, hepatore-
nal insufficiency. Bile stasis may compli-
cate with the inflammation of the bile
ducts (cholangitis), and when the pro-
cess becomes chronic, biliary cholestatic
cirrhosis may develop.
Hemomelanosis occurs in malaria.
A deposition of hemomelanin (malarial
pigment) occurs in organs and tissues,
both at the intracellular and extracellular
levels (in the spleen, bone marrow, liver, Fig. 2–26. Cerebral hemomelanosis in malaria
lymph nodes, as well as in the brain in (hematoxylin–eosin stain; ×110).
cases of malarial coma). The pigment
appears under the action of malaria plas- regulate the metabolism of porphyrins
modia, which parasite in erythrocytes. in erythroblasts and liver. An increase
At the same time, hemosiderin and bili- of porphyrins in the blood and urine
rubin are deposited. The affected organs and their deposition in the tissues occur.
get a dark grayish nuance. Granules of Erythema, photodermatitis, ulcerations,
hemomelanin in macrophages can be scars, depigmentated foci are observed
revealed at the microscope (Fig. 2–26). on the skin, in the liver – fatty dystrophy
Porphyria may be congenital or of hepatocytes, depositions of hemosi-
acquired: derin, in bones and teeth - a brown co-
a) Congenital porphyria is cau- loration.
sed by disturbances of metabolism of b) Acquired porphyria is noticed in
porphyrins in the body, as a result of intoxications, avitaminoses.

hereditary insufficiency of enzymes that
2.6.1.2. DYSTROPHIES OF PROTEINOGENIC PIGMENTS

Melanin (from the Greek melas – histiocytes that phagocytize melanin).
black) is a pigment of a brown – black At the microscope, it has an aspect of
color, which in physiological conditi- fine granules situated intra – or extra-
ons is contained in the skin, hair, ocular cellularly. It is not different from other
membranes (choroid, iris, retina), brain, pigments (hemosiderin, lipofuscin) at
leptomeninges. The pigment determi- usual staining with hematoxylin–eosin.
nes the coloration of the skin, hair and The reaction Fontana–Masson with an
eyes. It is formed exclusively in melano- ammonia solution of silver nitrate is
cytes by oxidation of tyrosin in dihydro- used to make a differential diagnosis.
xyphenylalanine (DOPA), the reaction Melanin reduces the silver nitrate to
being catalyzed by tyrosinase. Although metallic silver, seen at the microscope
it is synthesized only in melanocytes, it as granules of black color. The pigment
is also accumulated in keratinocytes of has a protective role: it protects the skin
the basal layer of the epidermis and in from ultraviolet radiation action. When
dermal macrophages (melanophages – exposed to the sun, the melanin synthe-

sis increases, that being a protective bi- can be explained by the fact that, as a re-
ological reaction. The content of mela- sult of destruction of the adrenal glands
nin varies much according to individual and diminution of the amount of adre-
and racial features. The melanogenesis is nal hormones in the blood, an increase
controlled by the central nervous system of ACTH secretion takes place, which
and endocrine glands. The disturbances exerts a melanocyte–stimulatory action
of melanin metabolism manifest them- and intensifies the synthesis of melanin
selves by hyperpigmentation (hyper- in the skin. The hypermelanosis of the
melanosis, melanodermia) or hypopig- skin occurs in other endocrine diseases
mentation (hypomelanosis) and each (hypogonadism, hypopituitarism), he-
of them can be generalized or localized, mochromatosis, avitaminoses (pellagra,
acquired or congenital. scurvy) and cachexies.
The most characteristic example of The generalized congenital hyper-
generalized acquired hypermelano- melanosis or xeroderma pigmentosum is
sis is the Addison disease. The skin in a hereditary disease, with a familial cha-
this disease turns intensively pigmented, racter, caused by congenital deficiency of
getting a bronzed aspect. At the micro- endonuclease - the enzyme regulating
scope, is observed increased quantities the repairing processes of the DNA de-
of melanin in cells of the basal layer of fects, as a result of ultraviolet radiation
epidermis, numerous melanophages fil- action. It manifests itself by hypersensi-
led with melanin granules in the subepi- tivity to the sunlight. It is characterized
dermal areas of the dermis (Fig. 2–27). by hyperpigmentation of the skin in the
form of spots that are more emphasized
on uncovered parts of the body, exposed
to sun radiations, ulcerations, atrophies,
scars, deformations. It is a precancerous
condition.

The local acquired hypermelanoses
have different variants of spots or hyper-
pigmented areas, for example:
ØØ ephelides (freckles) – small pigmen-
ted spots (1–10 mm), which appear
after exposing to the sunlight and
are particularly characteristic for pe-
ople with blond or red hair and bear
a seasonal character; at the micro-
Fig. 2–27. Hyperpigmentation of the skin in scope, the number of melanocytes is
Addison disease (hematoxylin–eosin stain, normal, but the content of melanin
×110). in the keratinocytes of the basal layer
It is caused by chronic insufficiency of epidermis is increased;
of the adrenal glands, i.e. abolition or di- ØØ lentigo – spots of 5–10 mm, which
minution of the hormones production of do not become more pigmented un-
these glands. The most frequent causes der the action of the sun radiation;
are: tuberculosis of adrenal glands (in at the microscope, is observed the
more than 70% of cases), amyloidosis, hyperplasia of melanocytes and their
primary or bilateral metastatic tumors hyperpigmentation;
etc. The hyperpigmentation of the skin ØØ hyperpigmentated areas of the skin,

which appear in ovarian tumors, as a calization is at the skin level, but there
result of a prolonged use of hormo- can be extracutaneous localizations. In
nal contraceptives, during pregnancy malignant melanoma, there is a synthe-
(chloasma or melasma of the preg- sis of some excessive quantities of me-
nant women); lanin, which is also present in hemato-
ØØ acanthosis nigricans – the appea- genic metastases of melanoma that can
rance of some pigmented patches, be localized in various organs and tissues
most frequently located in the flexu- (Fig. 2–29).
ral parts of the body (axillary, nape, The hypomelanosis can be gene-
anorectal, inguinal regions), in endo- ralized or localized. Generalized hypo-
crinopathies (diabetes mellitus, pi-
tuitary adenoma, hyperthyroidism),
and, in some cases, it is associated
with certain forms of cancer of the
visceral organs, being a manifestati-
on of the paraneoplastic syndrome.
Another example of local hyperme-
lanosis is the pigmentary nevi, conside-
red congenital or acquired hamartoma
of the skin (a hamartoma is a pseudo-
tumoral formation, consisting of cells Fig. 2–29. Melanoma metastasis in the brain.
and tissues - normal components of the
pigmentation or albinism appears as a
given organ). Macroscopically, they look
result of hereditary insufficiency of the
like spots or papules of up to 6 mm in
tyrosinase, which catalyzes the formati-
size, with smooth or verrucous surface,
on of melanin from tyrosine. It is cha-
of brown or dark–brown color, some-
racterized by the absence of melanin in
times covered with hairs (Fig. 2–28).
hair, skin, iris and retina. People have
Microscopically, it represents an agglo-

pale teguments, the hair is blond-white,
meration of nevic cells – cells that come
the iris and the choroid are depigmented,
from Schwann cells and can synthesize
the pink eyeground turning visible with
melanin.
naked eye. The microscopic and electro-
The malignant melanoma is another
noptic examination shows that melano-
example of local acquired hypermela-
cytes exist in a normal number and have
nosis. It is one of the most malignant
a normal structure, the pre-melanosomes
tumors in humans. A more frequent lo-
being present, but without melanin. Pa-
tients with oculo-cutaneous albinism
have severe photophobia, an extremely
sensitive skin to sun radiation, photoder-
matitides, ulcerations and a high risk of
squamous or basal cell cancer of the skin.
The localized hypomelanosis is cal-
led leucodermia or vitiligo (partial albi-
nism). It is manifested by the appearan-
ce of some white spots of different shape
and size, sometimes symmetrical, clearly
defined, surrounded by a hyperpigmen-
Fig. 2–28. Pigmentary nevus.
ted border most of the times (Fig. 2–30).

It may occur in some endocrine diverse inflammatory and necrotic lesions
seases (hyperparathyroidism, thyrotoxic of the skin (in burns, syphilis, leprosy).
Vitiligo may have an autoimmune ori-
gin, being caused by the appearance of
autoantibodies against tyrosinase or me-
lanocytes. Electron microscopic studies
revealed a reduction of the number of
melanocytes in affected areas, in com-
parison to albinism, where melanocytes
are present, but are not functional. The
localized melanin depigmentation may
Fig. 2–30. Leucodermia (vitiligo).
be congenital.
goiter, diabetes mellitus) related to me-
lanogenesis disorder, as a result of di-
2.6.1.3. DYSTROPHIES OF LIPIDOGENIC PIGMENTS

The main pigments of this group are It consists of complex lipids (pho-
lipofuscin, ceroid and lipochromes. spholipids) and proteins, which appear
The lipofuscin (from the Latin as a result of peroxide oxidation of unsa-
fuscus – yellow) is an insoluble intra- turated lipids of subcellular membranes
cellular pigment, in the form of fine in autophagia process of the own degra-
yellow–brown granules, placed in cyto- dated and aged components of the cell.
plasm mostly in the perinuclear space The accumulation of lipofuscin in or-
(Fig. 2–31 and 2–32).
Fig. 2–31. Liver lipofuscinosis (hematoxylin– Fig. 2–32. Myocardial lipofuscinosis (hemato-
eosin stain; ×110). xylin–eosin stain; ×110).
gans and tissues – the acquired lipofus-
cinosis - occurs in cachectic diseases,
senile atrophy, hypoxia and is observed
more frequently in myocardium, liver,
brain, adrenal cortex. Macroscopically,
the tissues and respective organs get
a brown appearance, hence the name
brown atrophy (Fig. 2–33). Due to this,
lipofuscin is also called “wear and tear
pigment” or “age pigment”.
Fig. 2–33. Brown atrophy of the heart.

The ceroid (from the Latin cera – Exogenous pigmentations. The

wax) is a lipopigment, which appears in inclusions of coal dust, which enter the
macrophages, as a result of phagocytosis organism by respiration, occur most
of some products containing lipids. The frequently. The inhaled dust is phago-
lipids are not disintegrated by lysosomal cyted by alveolar macrophages and taken
enzymes and remain in cells, forming lymphatically to the tracheobronchial
residual bodies – telolysosomes. It is most- lymph nodes. The pigment accumula-
ly formed in the necrosis of tissues, for tions give the lymph nodes and pulmo-
example, in the liver - in acute viral hepa- nary parenchyma a black color. A pro-
titis (in the resorption phase) or in granu- longed inhalation of the coal dust causes
an occupational pathology of respiratory
lation tissues in the course of maturation.
system – anthracosis - morphologically
The difference between lipofuscin manifested by pneumosclerosis and pul-
and ceroid is not distinct; the first lipo- monary emphysema.
pigment appears in parenchymatous cells Tattooing is an exogenous localized
of the organs, as a result of autophagy, the pigmentation of the skin. The respecti-
second – in macrophages, as a result of ve stain, when introduced into the skin,
heterophagy processes. is phagocyted by the macrophages from
The lipochromes determine the dermis, where it remains forever.
yellow coloration of the adipose tissue, Exogenous pigmentation of the skin
ovarian corpus luteum, adrenal cortex, may also occur in persons working with
testicles, blood serum and transudate. different chemical dyes.
2.6.2. DYSTROPHIES OF NUCLEOPROTEINS
The metabolic disturbances of nu- mas, which lead to an increase of the
cleoproteins manifest themselves by uric acid level in the blood. Secondary
excessive formation of uric acid and its gout may appear related to an exaggera-
salts, which can be stored in tissues. It ted consumption of animal proteins.
can be observed in gout and urinary li- The pathognomonic lesion is the
thiasis especially. gouty tophus that presents depo-

Gout (podagra) is characterized by sits of salts of uric acid, crystalline or
hyperuricemia and hyperuricuria. There amorphous, surrounded by perifocal
are 2 forms of gout: primary (idiopathic) reactive inflammation with macropha-
and secondary. Primary gout, the most ges, lymphocytes, fibroblasts, and giant
frequent form, constitutes 90% of cases. polynucleated cells “of foreign bodies”
It is caused by congenital, hereditary (Fig. 2–34 a).
disturbances of the purine metabolism.
A hyperproduction of uric acid with its
normal excretion takes place, or its nor- 2
mal production with a reduced elimi- 1
nation. Alcohol and obesity constitute
predisposing factors. A disorder of the
activity of enzymes involved in uric acid
metabolism can be observed in a certain
number of cases.
Secondary gout is noticed in 10% of 2
cases and can be a complication of some Fig. 2–34 a. Gouty tophus - microscopic pattern
diseases with massive cellular destructi- (hematoxylin–eosin stain; ×70): 1 – urate de-
ons, for example, in chronic hemolysis, posits, 2 – giant polynucleated cells of foreign
polycythemia, leukemias and lympho- bodies.

Subsequently, sclerosis processes
develop, painful nodules form and
deformation of joints may appear
(Fig. 2–34 b).
The elbow, knee, fingers joints are
affected, as well as the ear. Urate salts
of sodium are deposited in the synovi-
al membranes, cartilages, tendons, liga-
ments, articular capsule. 90% of patients
with chronic gouty arthritis develop
renal lesions: acute or chronic nephro-
Fig. 2–34 b. Gouty nodules (gouty tophi), pathy, urinary calculi.
macroscopic aspect.
2.6.3. MINERAL DYSTROPHIES. PATHOLOGIC CALCIFICATION
Disturbances of calcium metabolism

prevail among mineral dystrophies. The
main factors which ensure the main-
tenance of the normal calcium level in
organism are: the parathormone, calci-
tonin, food intake, vitamin D, as well
the function of calcium excretory organs
(kidneys, colon). Calcium is revealed in
histological section by von Kossa reacti-
on with silver nitrate. Pathological calci- Fig. 2–35. Dystrophic calcification of pulmo-
fication manifests itself by abnormal de- nary tissue (hematoxylin–eosin stain; ×70).
positions of calcium salts in soft tissues.
There are two variants of calcification:

a) dystrophic and b) metastatic.
Dystrophic calcification (petrifica-
tion) occurs in nonviable, necrosed tissu-
es, the calcium level in the blood plasma
being normal. The development mecha-
nism consists in physico–chemical chan-
ges of tissues in foci of dystrophy, necro-
sis, sclerosis, which stimulate calcium Fig. 2–36. Dystrophic calcification of coronary
absorption from blood and interstitial artery in atherosclerosis (hematoxylin–eosin
fluid. Local increase of alkalinity of tis- stain; ×110).
sues and of the activity of phosphatases
occur, and this favors the calcium absor-
ption and precipitation. Dystrophic cal-
cification has a local character. It can be
seen in tuberculosis (in foci of caseous
necrosis) (Fig. 2 –35), syphilis (syphili-
tic gummas), atherosclerosis of arteries
(Fig. 2–36), foci of necrosis (Fig. 2–37),
infarctions, scars (cutaneous keloids,
postinfarction scars), adherences, mor- Fig. 2–37. Dystrophic calcification of striated
tified parasites (echinococcus), cardiac muscle (hematoxylin–eosin stain; ×110).

valvulopathies. Macroscopically, the foci

of calcification have a whitish color and
a stony consistency. Microscopically, cal-
cium is revealed both intra and extra-
cellularly.
Metastatic calcification (calca-
reous metastases) is caused by excess
of calcium in blood plasma (hypercal-
cemia), determined, in its turn, by the Fig. 2–38. Metastatic calcification of myocar-
mobilization of calcium from bones or dium (hematoxylin–eosin stain; ×110);
by disturbance of elimination processes
of calcium from the organism. It is ob-
served in primary hyperparathyroidism
(parathyroid adenoma) or secondary
one (as a result of ectopic secretion of
parathormone in malignant tumors, for
example, in pulmonary cancer, bone tu-
mors (multiple myeloma, bone metasta-
ses), multiple bone fractures, hypervita-
minosis D, osteoporosis, osteomalacia, Fig. 2–39. Metastatic calcification of kidney
chronic nephritis. (hematoxylin–eosin stain; ×110), deposition of
Morphologically, it is manifested calcium salts in the renal tubes and in stroma.
by appearance of calcium focal deposits of calcium salts (the stomach - hydro-
(metastases) in different intact organs chloric acid, the kidneys – uric acid, the
and tissues, but more frequently - in lungs – carbon dioxide and the myocar-
arterial walls (tunica media), lungs, gas- dium and arteries are in constant contact
tric mucosa, myocardium, kidneys) (Fig. with the arterial blood and have a low
2–38 and 2–39). content of carbon dioxide). Macrosco-
There is a local alkalosis in these pically, calcium deposits have the same
organs, because they eliminate acidic aspect of whitish foci of a hard consis-
products, encouraging the precipitation
tency, like in dystrophic calcification.
2.6.4. CALCULOGENESIS (LITHIASIS)

Calculi or concrements are formati- play a certain role. The association
ons of dense consistency, which are for- of the biliary calculosis with obesity,
med in the lumen of hollow organs or atherosclerosis and of the nephroli-
in excretory ducts of glands, being con- thiasis with gout is well-known.
stituted of secretion components of the ²local factors:
respective organs or ducts. 1) inflammatory lesions of hollow/
Calculi appearance, the calculogene- tubular organs;
sis, is determined by a range of general 2) disorder of secretion and reab-
and local factors: sorption processes, leading to
²general factors: lipidic, mineral, pro- change of physicochemical fea-
teic, glucidic metabolism disturban- tures of secret, the increase of
ces. The character of alimentation, concentration of certain com-
the quality of drinking water, the ge- ponents and their precipitation
ographic area, the hereditary factors from the solution;

3) retention of secretion, its con-
densation due to the reabsorpti-
on of fluid components.
The presence of some nuclear fac-
tors like cellular debris, necrotic residu-
als, mucus, bacteria, leukocytes, desqua-
mated cells is important and constitutes
the organic matrix in which the salts are
deposited. Fig. 2–40. Calculi in gallbladder.
Most frequently, calculi are formed
in biliary and urinary ducts. Macrosco-
pically, they can have different sizes,
shapes, and colors, smooth or rugged,
granular surface, hard consistency. They
can be solitary or multiple numerically
(Fig. 2–40 and 2–41).
According to chemical structure,
biliary calculi may be cholesterolic, pig-
mented or mixed. Biliary calculosis may
complicate with cystic duct obstruction,
retention of bile and development of Fig. 2–41 Urinary calculus in renal pelvis with
gallbladder hydrops or mucocele, appea- hydronephrosis (dilatation of calyces).
rance of acute or chronic cholecystitis, vis and calyces, atrophy of renal paren-
perforation of vesical wall and over- chyma, repeated hydronephrosis; urete-
flowing of bile in peritoneal cavity with ral calculi cause hydroureter. It is usually
consecutive biliary peritonitis. associated with chronic pyelonephritis.
According to chemical composition, Calculi can also form in other

urinary calculi are frequently formed of hollow/tubular organs, for example, in
calcium oxalate, calcium phosphate, uric bronchi (broncholiths), pancreatic ducts
acid and its salts (oxalates, phosphates (pancreatoliths), salivary glands (sialoli-
and urates). Renal pelvis calculi cause
ths), intestine (coproliths).
the retention of urine, distention of pel-
ESSENTIAL TERMS
on the subject “MIXED EXTRA- AND INTRACELLULAR LESIONS (mixed dystrophies)”
acanthosis nigricans gout leucodermia

Addison disease gouty tophus lipochrome
albinism hamartoma lipofuscin
anthracosis hematin lipofuscinosis
bilirubin hematoidin mechanical jaundice
broncholithiasis hemochromatosis melanodermia
calcification hemolytic jaundice melasma
metastatic
calculogenesis hemomelanin
calcification

ceroid hemomelanosis nephrolithiasis

chloasma hemosiderin nevus
cholelithiasis hemosiderosis podagra
chromoproteins hepatic jaundice porphyria
coprolithiasis hydrochloric hematin porphyrin
dystrophic calcification hypermelanosis sialolithiasis
ephelides hypomelanosis urolithiasis
ferritin lentigo vitiligo
TESTS
on the subject “REVERSIBLE EXTRACELLULAR AND CELLULAR LESIONS”
SET I.
Multiple-choice questions with only one b) the lung;
correct answer c) the bone marrow;
1) Which process induces the development of d) the parathyroid glands;
generalized hemosiderosis: e) the kidneys.
a) extravascular hemolysis; 4) Variant of tissular calcification, according to
b) hemorrhages by diapedesis; the development mechanism:
c) intravascular hemolysis; a) atrophic;
d) hemangioma; b) necrotic;
e) mechanical jaundice. c) dystrophic;
2) Indicate the lipidogenic pigment: d) diffuse;
a) porphyrin; e) local.
b) the "wear and tear" pigment; 5) In which of the listed diseases occurs the im-
c) hemomelanin; pairment of nucleoproteic metabolism:

d) hemosiderin; a) hemosiderosis;
e) bilirubin. b) hemochromatosis;
3) Which organ participates in the regulation c) gout;
of calcium metabolism: d) Gaucher disease;
a) the liver; e) amyloidosis.
SET II.
Multiple – choice questions with 2, 3 d) it occurs in subcutaneous hemorr-
and more correct answers hages;
1) Which of the listed signs are characte- e) intoxications with hemolytic toxins.
ristic for local hemosiderosis: 2) Which of the listed causative factors may
a) it can be seen in chronic venous sta- cause the accumulation of lipofuscin in or-
sis in the lungs; gan:
b) intravascular hemolysis of erythro- a) arterial hyperemia;
cytes; b) cachectic diseases;
c) extravascular hemolysis of erythro- c) atrophic processes;
cytes; d) the aging of the body;

e) perivascular hemorrhages. b) deposition of calcium salts in joints;
3) Localization of deposits of fat in heart lipo- c) deposition of uric acid salts in joints;
matosis: d) hyperuricemia;
a) under epicardium; e) formation of nodules in the area of
b) in cytoplasm of cardiomyocytes; joints;
c) in walls of coronary arteries; f ) increase of the uric acid in the urine.
d) in walls of lymphatic vessels; 5) What changes in organs and tissues antici-
e) in stroma of myocardium; pate dystrophic calcification:
f ) under endocardium. a) mucoid intumescence;
4) Which of the listed signs characterize the b) necrosis;
gout (podagra): c) hyalinosis;
a) increase of the urea level in the d) severe dystrophy;
blood; e) hemosiderosis.
SET III.
The classification tests include 2 – 4 sub- 3. In which organs (tissues) do the lipidogenic
jects and a series of answers. Indicate which pigments accumulate:
answers are correct for each separate sub- I – lipofuscin;
ject. II – lipochrome;
1. Which hemoglobinogenic pigments are for- a) the ovarian corpus luteum;
med in the organism in: b) myocardium in decompensated
I – physiological conditions; valvulopathies;
II – pathological conditions; c) adrenals;
a) hematoidin; d) blood serum;
b) hemosiderin. e) the liver in cachectic diseases;
f ) the liver and other organs in se-

c) porphyrin;
d) ferritin; nile period.
e) bilirubin; 4. Which of the listed signs are characteristic for
f ) hematins. calcification:
2. Which of the listed sings characterize: I – metastatic;
I – hemosiderin; II – dystrophic;
II – hematoidin; a) hypercalcemia;
a) yellow color; b) normal level of calcium in the
b) brown color; blood;
c) is formed in 24 – 48 hours after c) systemic deposits of calcium
hemorrhage; salts;
d) is formed in 5 – 10 days after he- d) focal deposits of calcium salts.
morrhage; 5. Which of the listed diseases may cause:
e) is formed in the presence of I – mechanical jaundice;
oxygen; II – gallbladder hydrops;
f ) accumulates extracellularly; a) occlusion of common hepatic
g) is formed intracellularly. duct by calculi;

b) occlusion of choledoch duct by e) chronic cholecystitis with steno-

calculi; sis of the cystic duct lumen.
c) duodenal papilla cancer;
d) cancer metastases in subhepatic
lymph nodes;
Daily practice cases are presented with inful nodules was revealed. A nodule was
clinical and morphological data from clini- removed for diagnosis purposes. A histolo-
cal histories and/or from necropsy protocols. gical examination revealed focal deposits of
Each subject includes simple or multiple - crystals and amorphous masses, surrounded
answer questions, with 1, 2 or more correct by gigantocellular inflammatory reaction.
answers.
Questions:
1. A sportsman had a trauma of the soft tissues
A) Which disease can be suspected in this pati-
in the region of the hip, during his training.
ent:
On the second day, the area became bluish-
a) rheumatic arthritis;
grey, and, in a week, it became yellow, later
b) gout;
- greenish.
c) rheumatoid arthritis;
Question: d) exostoses;
Which hemoglobinogenic pigments were e) osteoporosis.
formed in the region of trauma: B) Which biochemical investigation of blood
a) hematoidin; and urine is indicated to specify the dia-
b) hemomelanin; gnosis:
c) hemosiderin; a) calcium content;
d) lipofuscin; b) uric acid content;

e) bilirubin. c) sodium content;
2. At a microscopic examination of cardi- d) potassium content;
omyocytes and hepatocytes of a patient who e) ketone bodies content.
died of pulmonary cancer, pigment granules 4. A patient, who suffered from multiple mye-
of brown color, which did not stain positive loma that affected vertebrae, ribs, skull bo-
at Pearls reaction, were revealed. nes, died of renal failure. At microscopical
examination of cadaveric material, foci of
Question:
calcification in myocardium and kidneys
Which pigment was detected in this case: were revealed.
a) melanin;
b) hemomelanin; Questions:
c) hemosiderin; A) Which calcification variant had this pati-
d) lipofuscin; ent:
e) lipochrome. a) metastatic;
3. A patient addressed a traumatologist be- b) dysfunctional;
cause of pains in the small joints of hands c) dystrophic;
and legs. During a clinical examination, d) metabolic;
a deformation of the fingers and some pa- e) physiological.

B) In which organs can be revealed foci of cal- a) choledoch duct;
cification in this case: b) common hepatic duct;
a) stomach; c) cystic duct;
b) lungs; d) intrahepatic ducts;
c) skin; e) duodenal papilla.
d) arteries; B) Which variant of jaundice has this patient:
e) brain. a) hemolytic;
5. A patient suffering from biliary lithiasis b) subhepatic;
started to feel pains in the right costal part c) hepatic;
and jaundice. d) prehepatic;
e) parenchymatous.
Question:
A) Which localization of calculi can be suspec-
ted in this patient:

Chapter 3 IRREVERSIBLE CELLULAR LESIONS NECROSIS AND APOPTOSIS
IRREVERSIBLE CELLULAR LESIONS

NECROSIS AND APOPTOSIS
3.1. NECROSIS
Necrosis is the localized death of cell; at this stage, cellular death

cells and tissues in a living organism. It signs can be revealed at electron
may include a portion of cell, separate and optical microscopy (the ap-
cells, cell groups, segments of tissues pearance of morphological signs
and organs or entire organs, parts of the of cellular death is called necro-
body. The necrotic process has an evolu- phanerosis); the exact moment of
tion of 4 stages: death of the cell (a non – return
1) pre-necrosis stage – the state of point of viability of a biological
the cell/tissue preceding the ne- object) cannot be established with
crosis; it includes potentially re- certainty, because different cellular
versible cellular lesions, which elements die at different periods
occur as a result of the action of of time;

harmful exo - and endogenous 4) autolysis stage (postnecrosis) – di-
factors; sintegration and lysis of necrotic
2) necrobiosis stage – a transition cells, under the action of the own
period from life to death, which hydrolytic lysosomal enzymes of
shows the evolution of cell to ne- necrotic cells (autolysis) and of
crosis. There is a progressive accu- neutrophil leukocytes and macro-
mulation of irreversible lesions of phages (heterolysis).
structural components in the cell, Necrosis can be conditioned by di-
but it remains viable as a system fferent causative agents, both of exoge-
and may restore in favorable con- nous and endogenous origin. According
ditions. This stage may lack in ca- to the etiological factor, the following
ses when necrosis occurs suddenly, varieties can be distinguished:
due to the action of some strong a) traumatic necrosis – caused by the
destructive factors, for example, action of some physical or che-
the electric power, but it may last mical factors (mechanical trauma,
for a long time; thermal or chemical burns, chilbla-
3) necrosis stage – morphological ins, radiation sickness etc.);
manifestation of the death of the b) toxic necrosis – caused by the acti-

IRREVERSIBLE CELLULAR LESIONS NECROSIS AND APOPTOSIS Chapte r 3
on of some bacterial toxins, exo- or tuberculosis), autoimmune diseases
endogenous toxic chemical sub- (disseminated lupus erythematosus,
stances, enzymes, drugs, etc. (in autoimmune glomerulonephritis etc.)
some infectious diseases, acute massi- According to the action mechanism
ve necrosis of the liver, acute tubular of the harmful agent, the necrosis can
renal necrosis, steatonecrosis, etc.); be direct and indirect. In case of direct
c) trophoneurotic necrosis – caused necrosis, there is a direct action on the
by the impairment of the trophic tissues of different causative agents, for
function of the central and/or the example, in traumatic, toxic or allergic
peripheral nervous system (in tra- necrosis. The indirect necrosis occurs as
umatisms, tumors of brain, spinal a result of disturbance of tissues (cells)
cord, peripheral nerve trunks; ce- trophicity, for example, in trophoneuro-
rebral infarctions and hemorrha- tic or vascular necrosis.
ges; leprosy etc. (eschars, trophic Morphological changes of the cells
ulcerations, gangrene); and tissues in the necrosis process occur
d) vascular necrosis (circulatory, ische- as a result of destructive actions of ca-
mic) – caused by the reduction or talytic enzymes, which are released from
suppressing of arterial circulation lysosomes of necrosed cells (autolysis) or
in an organ or tissue; vascular ne- from the lysosomes of leukocytes (hete-
crosis of parenchymatous organs rolysis). Two competitive processes de-
is called infarction; velop: denaturation of proteins, disinte-
e) allergic necrosis – related to harm- gration and dissolution of the cells.
ful action of immune complexes, The microscopic changes in necro-
antibodies in a sensitized orga- sis occur at the level of the cells (nucleus
nism (immediate hypersensitivity and cytoplasm) and intercellular matrix.
reaction), for example, in allergic Changes of the nucleus (Fig. 3–1):

infectious diseases (rheumatism,
A B C
Fig. 3–1. Schematic presentation of the cellular nucleus changes in necrosis; a) karyopyknosis; b)
karyorrhexis; c) karyolysis.

²² karyopyknosis – condensation of relatively long time, after which karyor-

chromatin and shriveling of nucleus; rhexis may happen and later karyolysis.
the nucleus has a reduced volume, in- Cytoplasm lesions:
tensely basophilic, the membrane is ²² denaturation and coagulation of
wrinkled, shriveled, the karyoplasma cytoplasmic proteins (plasma coa-
is dense, compact and the nucleolus is gulation); the cytoplasm becomes
not differentiated (Fig. 3–2 and 3–3); eosinophilic, as a result of increased
²² karyorrhexis – fragmentation of the acidophilia of denatured proteins
nucleus (chromatin) in small granules, and of diminishing of cytoplasmic
spread in cytoplasm; DNA content. Intensive eosinophi-
²² karyolysis – dissolution of the nuclear lia of cytoplasm is also a marker–
chromatin in cytoplasm, as a result of sign of the cell necrosis (Fig. 3–3);
the action of endonucleases; the disa- ²² plasmorrhexis – fragmentation of
ppearance of the nucleus is the mar- cytoplasm in blocks (Fig. 3–5);
ker–sign of the cell necrosis (Fig. 3–4). ²² plasmolysis – liquefaction and hy-
These changes of the nucleus can be drolysis of cytoplasm (Fig. 3–6).
consecutive stages or independent forms The intercellular matrix registers
of the cellular nucleus reaction to harm- the tumefaction and liquefaction of gro-
ful action. Karyopyknosis may persist a und substance, disintegration and lysis
RE
N
V
M
Fig. 3–2. Necrosis of the cell; karyopyknosis Fig. 3–3. Karyopyknosis and eosinophilia of the
(electron microscopy; ×17500): N – nucleus, ER sarcoplasm of cardiomyocytes in acute myocar-
– endoplasmic reticulum; M – mitochondria; V dial infarction (the red arrow – leukocyte infil-
– vacuoles. tration) (hematoxylin–eosin stain ; ×110).
Fig. 3–4. Necrosis of the epithelium of renal con- Fig. 3–5. Waxy (Zenker) necrosis of striated
voluted tubes (hematoxylin–eosin stain; ×70). muscle (karyolysis and plasmorrhexis) (hema-
toxylin–eosin stain; ×70).

of fibrillar elements (collagenic, reticu- revealed only in 6–12 hours from the
lar and elastic fibers) under the action of onset of ischemia. These aspects have a
proteases and lipases. particular significance in the morpholo-
Following the destruction and au- gical diagnosis of sudden death.
tolysis of mortified tissues, a tissular de- The periphery of necrotic focus re-
bris is formed in the necrotic focus. It veals an edema area, hyperemia of vessels
is an amorphous substance, consisting of and infiltration with neutrophil leuko-
cells debris and degraded fibers. cytes – a zone of demarcation inflamma-
Microscopically, necrotic lesions tion (Fig. 3–7), determined by the action
are best revealed in the autolysis stage, on viable surrounding tissues of different
which is not identical to necrosis, but biologically active substances released in
morphologically usually coincides with the necrotic focus, both from necrotized
it. According to experimental data, ir- cells and from neutrophils and macro-
reversible changes in cardiomyocytes phages. The inflammation contributes
occur in 20 minutes from the moment to the delimitation of the affected zone
of alteration, in liver and kidney cells - and to the resorption of necrotic masses
in 25–40 minutes, but the first obvious with subsequent restoration (regenerati-
histologic signs of cellular death can be on) of injured tissues.
NF
NF

Fig. 3–6. Focal (partial) necrosis of cytoplasm of Fig. 3–7. Demarcation inflammation in myo-
cardiomyocyte (electron microscopy; ×10000); cardial infarction, leukocyte infiltration at the
NF–necrotic focus. limit between necrosis and persistent myocar-
dium (hematoxylin–eosin stain; ×70).
3.1.1. CLINICAL AND MORPHOLOGICAL FORMS OF NECROSIS
The following clinical and morpho- 6) steatonecrosis (fat necrosis);

logical varieties of necrosis are distingu- 7) waxy necrosis (Zenker);
ished: 8) fibrinoid necrosis;
1) dry or coagulative necrosis; 9) sequestrum.
2) wet or liquefactive necrosis; Dry necrosis (coagulative) is cha-
3) gangrenous necrosis (gangrene); racterized by predominance of densi-
4) infarction (vascular, ischemic ne- fication, denaturation and dehydration
crosis); (drying) processes of the tissues. It is
5) caseous necrosis; the most frequent form of necrosis; the

necrotic masses are dry, dense, of a whi-

tish–yellow color, they are not subject
to enzymatic decomposition for a long
time. It is considered that the action of
harmful factors and the intracellular
acidosis condition the denaturation not
only of the structural proteins, but also of
enzymes and that stops the cell autolysis.
Consequently, the necrotic focus main-
tains the outlines of the tissular elements.
It is more frequently seen in poor in wa-
Fig. 3–8 a. Ischemic infarction of the spleen: ter tissues, practically in all the organs
macroscopic aspect. and tissues, except the brain and spinal
cord. As a rule, it is caused by hypoxia
and ischemia. The typical coagulative
necrosis occurs in myocardial, lienal and
renal infarction (Fig. 3–8 and 3–8 b).
Wet necrosis (liquefactive or colliqua-
tive) prevails the processes of moistening,
liquefaction and autolysis of dead tissues;
the necrotic masses contain an increased
content of fluid, have a soft, flaccid con-
sistency similar to a porridge. It occurs in
tissues rich in water, in which hydrolytic
processes are particularly intense. Firstly,
Fig. 3–8 b. Ischemic infarction of the spleen:
microscopic pattern (hematoxylin–eosin stain;
it is found in brain and spinal cord in-
×70). farction (grey or white cerebral softening,
encephalomalacia, Fig. 3–9), but it can

also be seen in purulent inflammation
foci, for example, in abscesses.
Softening of necrotic tissues hap-
pens as a result of proteo- and lipolytic
lysosomal enzymes action, both from
necrosed and inflammatory cells. In
cerebral tissues, the softening and the
resorption of liquefied necrotic masses
condition the formation of cystic cavi-
ties, filled with a semi-fluid mass. The
fluid penetrates from the adjacent tissue.
Gangrene (gangrenous necrosis) is
the necrosis of the tissues in contact with
the external environment (air, bacteria).
The dead tissues have a grayish–brown
or black color. Preferential localization is
in limbs, superficial soft tissues, digestive
Fig. 3–9. Cerebral ischemic infarction (white tube, lungs, uterus and urogenital tract.
softening, encephalomalacia). The most frequent causes of the gan-

grene of limbs are: thrombosis, arterial
thromboembolism in atherosclerosis, di-
abetes mellitus, obliterating endarteritis.
It can develop in burns, chilblains, vibra-
tion disease etc.
There may be dry, moist and gas (an-
aerobic) gangrene.
The processes of drying, densificati-
on and shriveling of dead tissues prevail
in dry gangrene. The tissues become
dry, wrinkled, mummified, as a result of
evaporation or absorption of water by Fig. 3–10. Dry gangrene of the foot.
the normal neighboring tissues. They are
black and have a dense consistency; the-
re is an obvious line of delimitation (de-
marcation inflammation) between the
live and the dead tissue. The black color
is determined by the iron sulphite, which
appears after a contact of hemoglobino-
genic pigments with the atmospheric air
and hydrogen sulphide produced by bac-
teria in mortified tissues (Fig. 3–10).
In wet (moist) gangrene, the tis-
sues are tumefied, imbued with fluid,
have a soft consistency, a grayish–blue or
Fig. 3–11. Wet gangrene of the foot.
blackish color, a putrefaction smell and
the demarcation line is missing. It occurs

mostly in inferior limbs, in cases of dia-
betes mellitus (Fig. 3–11), in lungs as a
complication of pneumonias, pulmonary
abscesses and infarctions, in intestines -
in atherosclerosis of mesenteric arteries
(Fig. 3–12).
It develops as a result of the action
of saprophytic bacteria of putrefaction
(Bacteria fusiformis, putrificans, pro-
teus etc.), which become pathogenic in
dead tissues. Initially, a coagulative ne-
crosis develops and a bacterial infection
associates on its background. Due to the
action of bacterial proteolytic enzymes,
the autolysis and liquefaction of necro-
sed tissues occur. Clinically, a severe to-
xemia happens, caused by the absorption
of toxic products from deteriorated tis-
sues. Wet gangrene is encouraged by the Fig. 3–12. Gangrene of small intestine.
venous stasis.

A rare variant of wet gangrene is noma the predisposing factors. It is a necrosis of

or gangrenous stomatitis, which starts at neurotrophic origin.
the gum line of the mandible and spreads Infarction is a necrosis of paren-
progressively over the soft tissues of the chymatous organs, caused by arterial or
face, predominantly over lips and cheeks. venous circulation impairment (vascular,
It is observed in children with severe in- ischemic, angiogenic necrosis). It occurs
fections, nutrition disturbances and avita- in myocardium, lungs, brain, spleen,
minoses. It is caused by the putrefaction (Fig. 3–7 – 3–9), kidneys and rarely in
bacteria. liver, intestine. It develops as a result of
Anaerobic or gas gangrene deve- thrombosis, embolism, prolonged spasm
lops at contamination of affected tissues of arteries or functional overstrain of the
by bacteria from the anaerobic group of organ in conditions of insufficient blood
microorganisms (Clostridium perfringens, flow. It is the most frequent form of ne-
oedematiens, histolyticum, septicum etc.). crosis, observed in atherosclerosis of ar-
The gangrenated zone gets an emphyse- teries, arterial hypertension, arteritides,
matous aspect, it crepitates on palpation thrombotic endocarditis etc.
due to the infiltration with gas bubbles Caseous necrosis is most frequently
and it has a greenish–grey color and a fe- observed in tuberculosis, but also in
tid smell. The process extends extremely syphilis, Hodgkin disease, leprosy, in
fast in neighboring tissues along muscles, some mycotic granulomas. It is a vari-
connective tissues, vessels and other tissu- ant of coagulative necrosis. The necro-
es with their necrosis. The respective mi- tic masses have a dense consistency, a
croorganisms produce exotoxins, which yellowish–white color; they are friable,
determine a severe intoxication, favouring reminding macroscopically the dry chee-
the spreading of necrotic process. It con- se (“cheese like” aspect, Fig. 3–13). Histo-
stitutes a complication of open extended logically, the necrotic area is amorphous,
wounds, produced in war circumstances, microgranular, astructurated, eosinophilic
road or work accidents, with massive des- stained (Fig. 3–14). A complete loss of
truction of muscular and bone tissues. It architectonics of tissue is characteristic,

is considered an independent infectious the cellular and tissular structures disap-
disease (primary gangrene). pearing completely.
Decubitus or eschar is a variant of
gangrene. It has foci of necrosis in soft
superficial tissues of bluish–black color,
the skin often being ulcerated. It ap-
pears in severe cachectic patients, with
circulatory and neurological disturban-
ces, especially in areas exposed to local
and prolonged mechanical compressions,
especially above bony prominences, for
example, in sacral, trochanteric, scapular,
calcaneal regions etc. It can often be no- Fig. 3–13. Caseous necrosis of pulmonary tissue.
ticed in patients with malignant tumors,
severe infectious diseases, chronic cardi- Steatonecrosis (fat necrosis) – ne-
ac insufficiency, cerebrovascular diseases, crosis of the adipose tissue. It is a form
etc., patients who remain confined to bed of enzymatic necrosis caused by the ac-
for a long time and in the same position. tion of lipase and trypsin, released from
The irregularities of the bed, the folds of pancreatic acinar cells in case of acute
underwear and bed clothes etc. may be pancreatitis (pancreonecrosis). The lipase

LC
N
Fig. 3–14. Caseous necrosis of lymph node in Fig. 3–15 a. Steatonecrosis in acute pancreatitis
tuberculosis (hematoxylin–eosin stain; ×110): – macroscopic aspect.
N – necrotic focus; LC – giant polynucleated
Langhans cell.
penetrates adipocytes, induces their ne-
crosis and transforms the lipids in soaps
(calcium salts of the fatty acids), which
give the necrotic foci an aspect of stea-
rin spots of yellowish–white color, dense
consistency and a clear outline. In acute
pancreatitis, steatonecrotic foci are no-
ticed in pancreas, peripancreatic tissue,
omentum, epiploon and in the adipo-
se tissue from other areas (Fig. 3–15 a).
Microscopically, the adipocytes become Fig. 3–15 b. Steatonecrosis in acute pancreati-
unclear, with blurred outlines, basophilic tis - microscopic pattern (hematoxylin–eosin
colored (in blue), as a result of an incre- stain; ×70).

ased content of calcium salts (Fig. 3–15 ted more often. The necrotic masses are
b). It is also observed in traumatisms of infiltrated with plasmatic proteins, whe-
adipose tissues, for example, of mammary re the fibrin prevails (hence the name of
gland. fibrinoid necrosis); microscopically, they
In waxy necrosis (described by Zenker), have a homogenous, eosinophilic aspect
the necrotic masses have a dense consis- (Fig. 3–16).
tency (coagulation necrosis), a macrosco-
pic yellowish–white aspect, similar with
the bees-wax. It is observed in striated
muscles, in some severe acute infectio-
us diseases (typhoid fever, exanthematous
typhus), muscular traumatisms, electric
shock. Optical microscopy shows that
striated myocytes have a homogenous,
astructured aspect; the transversal striati-
on is missing (Fig. 3–5).
In fibrinoid necrosis, the connective
tissue is destructed (the ground substance
Fig. 3–16. Fibrinoid necrosis of vascular wall
and collagenic fibers). Arteries of small
in polyarteritis (periarteritis) nodosa (hemato-
caliber and stroma of organs are affec-
xylin–eosin stain; ×110).

It is usually seen in arterioles, small

caliber arteries and glomerular capillaries
in autoimmune diseases (for example, in
systemic lupus erythematosus, glome-
rulonephritis) and in malignant arterial
hypertension. The fibrinoid necrosis of
arterioles and small arteries is characte-
ristic in hypertensive crises (emergencies).
Sequestrum is a portion of dead a b
tissue, detached completely from viable
surrounding tissues and situated freely in Fig. 3–17. Chronic purulent osteomyelitis with
a sequestrial cavity (Fig. 3–17). It appears formation of sequestra; a – macroscopic aspect;
when the necrosed tissue is not exposed b – schematic presentation.
to autolysis, organization or encapsula-
tion. It often occurs in bones, multiple
fractures with small pieces, in tuberculo- cavity and fragments of necrosed bone
sis, sepsis. Sometimes, external fistulas are tissue can be eliminated. The sequestra-
formed – canals in soft tissues with ori- tion of Peyer’s patches in typhoid fever, of
fice at the skin level, through which the pulmonary infarction, eschars can occur,
pus is let out periodically from sequestrial etc.
3.1.2. EFFECTS AND CONSEQUENCES OF NECROSIS
The effects and consequences of aminotransferase (ALAT), in necrosis of

necrosis depend on the extension of exocrine pancreas – the level of amylase.
the necrotic process and functional im- The direct consequences of necrosis
portance of the affected tissues. For in- depend on the potential of regeneration
stance, the necrosis of convoluted tubes and the preexisting state of the deterio-
of kidneys leads to acute renal failure, rated tissues. Among the consequences
massive necrosis of the liver – to hepatic of necrosis we distinguish:
failure (coma), necrosis of cerebral tissue 1. Complete restoration of the pre-
– to paralyses, necrosis of myocardium existent tissue through regenerati-
– to impairment of the heart functions on (restitution). It is observed in
etc. Small size necrosis in the spleen, organs/tissues with the cellular
kidneys and lymph nodes may have mi- form of regeneration, for example,
nimum effects, without major functional in the liver, kidneys, mucosas.
disturbances. During necrotic processes 2. Organization (cicatrization) –
in different tissues and organs, there is a substitution of necrotic focus with
release of enzymes from necrotized cells, connective tissue, for example, in
which results in enzymemia – growth of myocardium, the necrotic debris
the level of some enzymes in the blood. is resorpted by phagocytes, and a
This phenomenon constitutes the basis connective tissue scar (substituti-
for clinical diagnostic tests of necrosis on) appears in the area of necrosis
of different internal organs. For exam- (Fig. 3–18 a, b).
ple, in myocardial infarction, the level 3. Encapsulation – formation of a
of creatine-phosphokinase (myocardial membrane (capsule) of connective
form – CK–MB) in the blood increases, tissue around the necrotic focus; it
in hepatic necrosis – the level of alanine- can be observed most frequently

in foci of caseous necrosis in tu-
berculosis (Fig. 3–19).
4. Calcification (petrif ication) – de-
posits of insoluble calcium salts in
necrotic masses (dystrophic calci-
fication). It is characteristic for ca-
seous necrosis in tuberculosis (Fig.
3–19), waxy necrosis of striated
muscles etc.
Fig. 3–18 a. Organization of myocardial infarc- 5. Ossification – substitution of ne-
tion (macrofocal postinfarction cardiosclerosis) crotic focus with newly- formed
– macroscopic aspect. bone tissue.
6. Formation of cysts (cystic trans-
formation) – appearance of some
cavities, as a result of lysis and
resorption of mortified tissue in
liquefactive necrosis (Fig. 3–20).
It is more frequently observed in the
brain and spinal cord. The newly-for-
CT med cavities are actually pseudocysts,
because they do not have an epithelial
lining and their wall is from the cerebral
Fig. 3–18 b. Organization of myocardial infarc-
tion (macrofocal postinfarction cardiosclerosis)
tissue adjacent with necrotic and softe-
– microscopic pattern: CT – cicatricial con- ning focus.
nective tissue (hematoxylin–eosin stain; ×110). 7. Sequestration – complete deta-
chment of the dead tissue from
the live one. It is mostly seen in

bone tissues (Fig. 3–17).
8. Autoamputation – complete de-
tachment from the organism of
some limbs or organs, for example,
in the dry gangrene of fingers.
9. Mummification – drying of
dead tissues in gangrene.
10. Purulent lysis – disintegration
Fig. 3–19. Encapsulated petrification in pulmo- (melting) of necrotic masses, un-
nary tissue. der the action of polymorphonu-
cleated leukocytes, in cases of pyo-
genic overinfection.
Organization, encapsulation, calci-
fication (petrification), ossification and
sequestration occur mostly in dry necro-
sis. Cysts formation and purulent lysis
are usually observed in wet necrosis. Au-
toamputation and mummification may
occur in dry gangrene.
Fig. 3–20. Postnecrotic cerebral cyst.

3.2. APOPTOSIS
The apoptosis is a specific, morpho- ²² elimination of cells in the tissues
logically distinct form of cellular death, that have a rapid cellular turnover,
which differs from the usual coagula- for example, in intestinal epithe-
tive necrosis. It is a programmed gene- lium.
tic process, controlled and energetically Examples of pathological apoptosis:
dependent, responsible for the inactiva- ²² elimination of the cells with de-
tion and elimination of over numerical, fects at DNA level, caused by
nonfunctional or deteriorated cells. Apo- viral infection, ionizing or ultra-
ptosis provides a permanent renewal of violet radiations, cytotoxic agents
tissues and the maintenance of structural (drugs) etc;
homeostasis in the human body. The eli- ²² destruction of virus-infected cells
mination of cells through apoptosis con- by cytotoxic T-lymphocytes, for
stitutes the main mechanism of cellular example, in viral hepatitis, the
death, both in physiological conditions cytotoxic T-lymphocytes have the
and in various pathological processes. ability to interact directly with
Examples of physiological apoptosis: the cytoplasmic membrane of the
²² elimination of excess cells during target cells, releasing substances
embryonic development of organs which induce the apoptosis in the
and tissues. An eloquent example virus-infected cells;
is the disappearance of interdigital ²² death of T-helper cells (CD4) in-
folds from the membranes of the fected with the human immuno-
embryo, which is occurred through deficiency virus (HIV infection);
apoptosis, and the disorder of this ²² elimination of neoplastic cells; the
process causes syndactylia (a con- balance between apoptosis and
genital defect consisting in fusing cellular proliferation is disturbed
in tumors;
the fingers and toes together);

²² elimination of cells in the involu- ²² death of nerve cells in neurodege-
tion of some organs (tissues), for nerative diseases (Alzheimer di-
example, in physiological involuti- sease, amyotrophic lateral sclerosis,
on of the thymus; Parkinson disease).
²² elimination of cells from hormo- Apoptosis is initiated by an intra-
ne-dependent tissues, such as the cellular signaling complex and a range
endometrium (changes of uteri- of enzymatic processes. The main role
ne lining in menstrual cycle), the belongs to the caspases – a group of pro-
mammary gland (involution of teolytic cysteinic enzymes, which act in
epithelium after cessation of lac- cascade (for example, the complement).
tation), the prostate (atrophy of They are present in cells in an inactive
prostate in case of decrease or abo- form and are activated by apoptotic sti-
lition of testosterone secretion) etc. muli. Some caspases activate, in their
²² clonal selection of lymphocytes turn, other caspases, which alter the com-
in the process of formation of ponents of the cytoskeleton, as well as
immunological tolerance, for the endonucleases that disintegrate the
example, deletion of autoreactive nuclear DNA, and phospholipases whi-
T-lymphocytes in thymus (which ch change the configuration of the cellu-
can react with their own tissues); lar membrane. Usually, apoptosis appears

in individual, solitary cells (the so-called leaves from the trees”). The splitting of the
“cellular suicide”). Initially, there is a disor- cell occurs in more fragments – apopto-
ganization of superficial structures in the tic bodies that contain cytoplasm, orga-
cell in apoptosis - the loss of microvilli nelles, pieces of nucleus and are covered
and intercellular junctions; the cell gets a by cytoplasmic membrane (Fig. 3–21).
spherical shape, it detaches from the ne- Apoptotic bodies penetrate the ex-
ighbor cells and isolates. Later, the cell tracellular space. In histological sections,
shrinks, diminishes in size, the nucleus they have an aspect of oval or round for-
shrivels. Chromatin condenses forming mations with an intensely eosinophilic
aggregates that stay in the marginal zone cytoplasm, containing fragments of nu-
of nucleus, along the membrane. Cyto- clear chromatin, mitochondria and other
plasmic organelles condense, but remain intact cytoplasmic organelles (Fig. 3–22).
intact from the structural point of view. In the final phase, apoptotic bodies
Concurrently, the cells form exvaginati- become recognized, phagocyted and di-
ons of cytoplasmic membrane because gested by both macrophage and paren-
of cytoskeleton alteration, which, later, chymatous neighboring cells. Apoptotic
break away from the cell body (hence the bodies can be eliminated via secretions,
name of apoptosis – in Greek “the falling of lymph or blood. The rapid clearance of
AB
AB

MP
I II III
Fig. 3–21. Schematic presentation of apoptosis: I – normal cell; II – shriveling of the cell and the
chromatin disposition under nuclear membrane; III – phagocytosis of apoptotic bodies; AB – apo-
ptotic bodies; MP – macrophage.
apoptotic remains (in several hours) pre-
vents the inflammatory response, beca-
use there is no draining of cytoplasmic
content in the extracellular space. The
absence of inflammatory reaction is an
essential feature of apoptosis, due to
which the death of one cell does not
affect the neighbor cells, the tissular and
cellular architectonics of adjacent tissue
remaining intact.
Apoptosis can be stimulated or in-
Fig. 3–22. Apoptosis of hepatocytes in acute vi- hibited by certain pro- or antiapoptotic
ral hepatitis (hematoxylin–eosin stain; ×110). factors, for example: the protein Bcl–2
(B–cell lymphoma) inhibits apopto-

sis, prevents the death of the lympho- tion between apoptosis and necrosis are
ma lymphocytes, transforming them exposed in table 3.1.
into “immortal” cells; the protein p53 The main difference between necro-
is an inductor of apoptosis: it regula- sis and apoptosis consists in the fact that
tes the DNA replication, proliferation necrosis is always a pathological process,
and death of cells. It is considered that while apoptosis occurs in normal, physi-
exactly this protein can prevent the ological conditions and does not obliga-
spreading of genetically altered cells in tory associate with necrosis. But still, in
tissues. The absence or mutation of p53 some pathological processes, both forms
protein was revealed in colon, pulmo- of cellular death can be involved. For
nary and mammary cancer and in other example, in the central zone of myocar-
malignant tumors. dial infarction, the processes of necrosis
The accumulation of cells through prevail, while the apoptosis prevails in
suppression of apoptosis may contribute the peripheral zone, where the intensity
to the appearance and evolution of neo- of hypoxia is lower.
plasms, to persistence of viral infections, Another form of genetically-pro-
and excessive death through apoptosis grammed cellular death is autophagia
may result in different degenerative di- (autodigestion). In the process of au-
seases. The main criteria of differentia- tophagia occurs the lysosomal autodi-
Table 3.1
APOPTOSIS versus NECROSIS
Criteria of differentiation NECROSIS APOPTOSIS
It may be caused by different
It is caused only by
Induction physiological and pathological
harmful factors.
factors.
Extension Groups of cells Solitary, individual cells
The lysosomes release Nuclear DNA fragmentation. The

Biochemical aspects
lytic enzymes lysosomes are intact.
Condensation of chromatin
Tumefaction and lysis
and fragmentation of nucleus,
Morphological pattern of the cell, cytoplasmic
formation of apoptotic bodies.
membrane is altered
Cytoplasmic membrane is intact.
Inflammatory reaction Present Absent

Phagocytosis of apoptotic bodies
Phagocytosis of dead
by parenchymatous neighboring
Consequences cells by neutrophils and
cells (“non–professional”
macrophages.
phagocytes) or by macrophages.
gestion of the own components of the produced. Later, the vacuoles fuse with
cell. Initially, the sequestration of some lysosomes, forming autophago-lysoso-
intracellular organelles and portions of mes, in which cellular components are
cytosol with formation of autophagic digested by lysosomal enzymes. The un-
vacuoles, delimited by the membrane digested remains are eliminated through
of the rough endoplasmic reticulum is exocytosis, and a part of them remains

in cytoplasm, like residual corpuscles. bolic and energetic substrates, which en-
The process of autophagia is regulated sure their survival in certain pathological
by a complex of cellular proteases na- conditions. Autophagia can be induced
med ubiquitins. Thus, an elimination by hypoxia, hormones and intracellular
of supernumerary, aged, degraded and stress, and is involved in some neuro-
altered organelles occurs. Autophagia degenerative diseases, myopathies, and
is also involved in the maintenance of tumoral processes. Currently, the au-
cellular homeostasis in conditions of in- tophagic death is considered the second
sufficiency of nutritive substances. Au- type of programmed cellular death (after
todigestion of own components in such apoptosis). Autophagia and apoptosis
conditions provides the cells with meta- can be independent or may coexist.
ESSENTIAL TERMS
on the subject ”IRREVERSIBLE CELLULAR LESIONS. NECROSIS AND APOPTOSIS”
agony dehydration myomalacia

apoptosis demarcation inflammation necrobiosis
apoptotic body direct necrosis necrosis
autolysis encapsulation noma
autophagia encephalomalacia organization
calcification (calcinosis) eschar ossification
caseous necrosis fibrinoid necrosis petrification
coagulative necrosis gangrene plasmolysis
colliquative necrosis indirect necrosis plasmorrhexis
Councilman corpuscle infarction purulent lysis
cyst karyolysis sequestrum

cytolysis karyopiknosis steatonecrosis
debris (cellular, tissular) karyorrhexis waxy necrosis
(Zenker)
decubitus mummification
TESTS
on the subject “IRREVERSIBLE CELLULAR LESIONS. NECROSIS AND APOPTOSIS”
SET I.
Multiple-choice questions with only one 2. What is the correct definition of gangrene:
correct answer. a) vascular necrosis;
1. Which of the changes of the nucleus charac- b) dry necrosis;
terize the karyopyknosis: c) toxic necrosis;
a) dilatation of endoplasmic reticu- d) necrosis of tissues in contact
lum cisternae; with the external environment;
b) margination of chromatin; e) allergic necrosis.
c) destruction of mitochondria; 3) Which of the listed diseases develop more
d) condensation of chromatin; frequently in wet gangrene:
e) size-increasing of nucleoli. a) atherosclerosis;

b) diabetes mellitus; d) traumatisms;

c) hepatic cirrhosis; e) reduction of arterial blood supply.
d) myocardial infarction; 5) Which etiological variant of necrosis occurs
e) arterial hypertension. in eschars:
4) Which of the listed causes induce the deve- a) vascular;
lopment of infarction: b) trophoneurotic;
a) autoimmune conflict; c) traumatic ;
b) damage of peripheral nerves; d) toxic;
c) action of some bacterial toxins; e) liquefactive.
SET II.
Multiple-choice questions with 2, 3 or b) encapsulation;
more correct answers. c) autoamputation;
1. Indicate the microscopic changes of the cells d) calcification;
cytoplasm in necrosis: e) formation of a cystic cavity.
a) coagulation; 4. The infarction can develop in which of the
b) karyorrhexis; listed organs:
c) plasmorrhexis; a) uterus;
d) plasmolysis; b) brain;
e) karyopyknosis. c) kidneys;
2. Characteristic signs of dry gangrene: d) vermicular appendix;
a) dense consistency of mortified e) liver.
tissues; 5. Caseous necrosis occurs more frequently in
b) dehydration of tissues; which diseases:
c) flaccid consistency of tissues; a) lobar pneumonia;
d) whitish color of tissues; b) gastric ulcer;
e) black color of tissues. c) Hodgkin disease;

3. Which consequences of necrosis occur more d) tuberculosis;
frequently: e) appendicitis.
a) organization;
SET III.
Classification tests include 2–4 subjects e) phagocytosis of cellular frag-
and a series of answers. Indicate the correct ments by adjacent cells;
answers for each subject separately. f ) phagocytosis of cellular debris by
1) Which of the listed signs characterize: emigrated blood leukocytes;
I – necrosis; g) disintegration of the cell in frag-
II – apoptosis; ments with intracellular organel-
a) absence of the inflammatory re- les and debris of nuclei, delimi-
action; ted by the membrane;
b) intact cytoplasmic organelles; h) appearance of perifocal in-
c) destruction of cytoplasmic or- flammatory reaction.
ganelles and cellular membrane; 2) In which organs and tissues occurs more of-
d) disappearance of cellular nucle- ten :
us; I – coagulative necrosis;

II – colliquative necrosis; b) tissues necrosis caused by circu-
a) limbs; latory disturbances;
b) myocardium; c) necrosis caused by an immune
c) spleen; conflict;
d) brain; d) necrosis in which processes of
e) liver; denaturation and dehydration of
f ) kidneys; tissues prevail;
g) spinal cord. e) necrosis of tissues contacting
3) Indicate which disease is characteristic for: with atmospheric air;
I – caseous necrosis; f ) necrosis in which mortified tis-
II – fibrinoid necrosis; sues cannot be phagocyted.
a) leprosy; 5) In which of the organs listed below may de-
b) tuberculosis; velop more frequently:
c) rheumatism; I – the gangrene;
d) arterial hypertension; II –the infarction.
e) Hodgkin disease; a) myocardium;
f ) syphilis. b) lungs;
4) Indicate the correct definition: c) intestine;
I – of infarction; d) limbs;
II – of gangrene; e) uterus;
III – of sequestrum; f ) vermicular appendix;
IV – of coagulative necrosis; g) gallbladder;
V – of colliquative necrosis; h) kidneys;
VI – of allergic necrosis; i) brain;
a) necrosis in which processes of j) palatine tonsils.
liquefaction and autolysis of
dead tissues prevail;

Daily practice cases are presented with c) karyolysis;

clinical and morphological data from clini- d) karyokinesis;
cal histories and/or from necropsy protocols. e) marginal hyperchromatosis of
Each subject includes simple or multiple - nucleus.
answer questions, with 1, 2 or more correct 2. The microscopic examination revealed rhe-
answers. umatic granulomatous myocarditis in a 38
1. The microscopic examination of the renal year-old patient, who died of chronic and
biopsy sampled from a patient suffering of progressive cardiac insufficiency. Granulo-
tuberculosis revealed foci of caseous necrosis mas from macrophages with a necrotic focus
with chromatin granules at periphery. in the center were revealed in myocardium
stroma.
Question:
At what stage of cellular nucleus lesions in Question:
necrosis do such changes appear: Which necrosis variant occurs in the center
a) karyopyknosis; of rheumatic granuloma:
b) karyorrhexis; a) fibrinoid;
b) steatonecrosis;

c) caseous; time. The epidermis was desquamated in

d) Zenker; some places and ulcerations were formed.
e) coagulative.
Question:
3. A 75 year-old patient was taken urgently
Which pathological process of the listed be-
to the hospital with symptoms of acute ab-
low occurs in this case:
domen. During laparotomy operation, the
a) apoptosis;
surgeon established that about 80 cm of the
b) dry gangrene;
small intestine had a black color, the perito-
c) infarction;
neum was opaque and in hyperemia, and
d) eschars;
the lumen of the superior mesenteric artery
e) wet gangrene.
was obstructed by thrombotic masses.
5. A chronic osteomyelitis with fistulae, throu-
Question: gh the orifices of which necrosed bone frag-
Which clinical and morphological variant ments are released, developed in a patient
of necrosis occurred in the intestine in this with an open comminuted fracture (with
case: more segments) of the leg bones.
a) eschar;
Question:
b) white infarction;
c) coagulative necrosis; Which of the listed necrosis variants occurs
d) gangrene; in this case:
e) white infarction with hemorrha- a) sequestrum;
gic border. b) gangrene;
c) infarction;
3. Areas of black color and edema appeared in
d) waxy necrosis;
the sacral, scapular, calcaneal regions of an
e) caseous necrosis.
elderly patient with a femoral neck fractu-
re, who has been confined to bed for a long

DISTURBANCES OF BLOOD AND LYMPHATIC CIRCULATION Chapte r 4
DISTURBANCES OF BLOOD
AND LYMPHATIC CIRCULATION
4.1. HYPEREMIA
Hyperemia is the increasing of can be arterial and venous, generalized

blood volume in an organ or tissue. It and local.
4.1.1. ARTERIAL HYPEREMIA
Arterial hyperemia consists in increa- Angioneurotic hyperemia appears as

sing of blood mass in an organ or tissue, a result of some innervation disorders
as a result of increased blood flow in arte- with exitation of vasodilator nerves or
ries. Macroscopically, it manifests itself by paralysis of the vasoconstrictor nerves.
a red color of teguments and increasing It may occur in some infectious diseases,

of local temperature, and, microscopically, like scarlet fever, typhoid fever, measles.
by active dilatation of arterioles. Collateral hyperemia appears in case
It may have a general character, when of occlusion of the magistral vessel with
the volumes of the circulating blood or a thrombus or embolus, when dilatation
the number of erythrocytes are increased, and hyperemia of collateral arteries occur.
and it may be local. Local arterial hypere- This reaction can compensate partially or
mia is more frequent and it may be obser- totally the ischemia caused by the occlu-
ved both in physiological and pathologi- sion of the magistral artery.
cal conditions. Examples of physiological Postanemic hyperemia is noticed in ca-
hyperemia may be: hyperemia of tegu- ses when a vessel has been compressed by
ments in different emotional conditions, a tumor, ligature, adherences, a collection
hyperemia of gastric and intestinal mu- of fluid etc. and, at a sudden removal of
cosa during digestion, hyperemia of mus- the respective factor, a rapid hyperemia
cles during a physical effort, hyperemia of of the previously ischemized area occurs,
skin under the action of the sun rays etc. which may result in rupture of vessels,
Arterial pathological hyperemia can hemorrhages. Besides these, there may
be: a) angioneurotic; b) collateral; c) pos- appear debilitation of other organs, like
tanemic; d) hyperemia ex vacuo and e) the brain, as a result of sudden redistribu-
inflammatory. tion of blood.

Chapter 4 DISTURBANCES OF BLOOD AND LYMPHATIC CIRCULATION
Hyperemia ex vacuo appears as a result applying cupping glasses on the skin.

of decrease of barometric pressure and it Inflammatory hyperemia is a mani-
occurs in divers and caisson workers, at festation of exudative phenomena in in-
their rapid lifting from high pressure to flammatory processes and constitutes a
the normal one; and has a generalized clinical sign characteristic for inflamma-
character. Local hyperemia conditioned tion.
by an analogical mechanism occurs when
4.1.2. VENOUS HYPEREMIA (OF STASIS OR CONGESTIVE)
Venous hyperemia is caused by the of veins and capillaries with an excess of
diminution of venous blood flow in con- blood in these vessels. It may be genera-
ditions of normal arterial circulation. It lized and localized, acute or chronic.
is manifested through passive dilatation
4.1.2.1. GENERALIZED VENOUS HYPEREMIA

It is a consequence of acute or chro- se changes are stereotyped and occur
nic cardiac insufficiency, based on the both in generalized and localized ve-
disturbance of the heart contractile ac- nous hyperemia. The main pathogenic
tivity (heart decompensation). mechanism of morphological lesions in
Acute cardiac insufficiency is observed venous hyperemia is the tissular hypoxia
in myocardial infarction, acute myocar- (venous or congestive hypoxia).
ditis, acute endocarditis with valvular The characteristic macroscopic as-
ruptures, hypertensive crisis etc. It is pects of the organs in chronic congestive
manifested by acute generalized veno- hyperemia are the following:
us hyperemia; the dilatation and hype- a) the dimensions and the mass are
remia of veins and capillaries appear in increased;
organs and tissues, as well as the plas- b) the capsule of organs is smooth,
matic infiltration (plasmorrhagia) and extended (under pressure);
edema, multiple perivascular hemorrha- c) the consistency is increased and
ges through diapedesis, dystrophic and dense;
necrotic lesions resulting from acute d) the color on the section is dark–
hypoxia and mechanical compression of red–purple – the color of deoxyge-
perivascular parenchymal elements by nated venous blood;
the dilated vessels. e) when sectioned, the blackish–red
Chronic cardiac insufficiency is ob- blood drains out abundantly from
served in chronic cardiac diseases, such the surface of the section.
as valvulopathies, cardiosclerosis, severe Changes of different organs and tis-
impairments of the rhythm and con- sues in chronic venous congestion (sta-
duction, chronic myocarditis, constricti- sis) have many common features and are
ve pericarditis etc. It manifests itself by named cyanotic or stasis induration. At
dilatation and chronic hyperemia of the the same time, certain specific features
veins, plasmorrhagia and edema, eryth- can be seen in some organs, which are
rodiapedesis, hemosiderosis, atrophy conditioned by their angioarchitectonic
and disappearance of parenchymal cells particularities, especially in the liver and
and sclerosis of organs and tissues. The- lungs.

The skin has a cyanotic aspect of tic (stasis) induration. The dimensions
bluish–violet color and a low tempera- and the mass of organs are increased,
ture; it is particularly clear seen in the the surface is smooth, the capsule is ex-
face area (nose, lips) (Fig. 4– 1). tended, under tension, the consistency
Fig. 4–1. Cyanosis of the face skin and mucosa Fig. 4–3. Cyanotic induration of the kidney
of lips. (stasis kidney).
The phenomenon is generated by is increased. The parenchyma has a dark
the deoxygenated venous blood in dila- red color on the section and the venous
ted veins and capillaries. It is a certain blood drains out abundantly (Fig. 4–3).
symptom of cardiac insufficiency. Microscopically, one observes the
The subcutaneous adipose tissue dilatation and hyperemia of glomerular
is edematous, tumefied. The lax tissues and peritubular capillaries, dystrophic
in the region of lower limbs, external ge- lesions of epithelium of convoluted tu-
nital organs, eyelids are affected more of- bes, excessive proliferation of connective
ten and intensely. Generally, the edema is tissue in the stasis kidney. At microsco-

more marked in the lower part of the body. pic examination of the spleen, the red
When pressed with a finger, a pitting de- pulp is extensively hyperemic, flooded
pression remains and does not disappear with blood, the sinuses are dilated, filled
for several seconds or minutes (Fig. 4–2). with erythrocytes; there can be hemorr-
Fig. 4–2. Edema of the lower limb, pitting symp- Fig. 4–4. Chronic venous hyperemia of the sple-
tom. en (hematoxylin-eosin stain; ×70).
A varicose dilatation of the veins, a hagic foci, the walls are fibrosed and the
skin hemosiderosis, trophic ulcerations white pulp is reduced and poorly highli-
may develop, which are hardly healed. ghted (Fig. 4–4).
The kidneys and the spleen – cyano- In the serous cavities accumulations

of edema appear – hydrops of the re- not changed, the trabecular structure is
spective cavities (hydrothorax, hydrope- maintained (the color of these areas is
ricardium, ascites or hydroperitoneum). brown–red macroscopically - the usual
The liver is enlarged in size and aspect of the hepatic parenchyma) (Fig.
mass, it has a smooth extended capsule, 4–5 b).
dense consistency, the anterior margin Selective hyperemia of central areas
is rounded with a very emphasized lo- of the lobules can be explained by the
bular pattern on section, a characteristic fact that venous stasis covers hepatic and
spotted aspect, similar with the Ameri- collecting veins firstly, and, at the lobu-
can nut kernel or nutmeg (Fig. 4–5 a), les level – the centrolobular and the ne-
1 2
Fig. 4–5 a. Chronic venous hyperemia of the Fig. 4–5 b. Chronic venous hyperemia of the
liver (nutmeg liver): macroscopic aspect: below liver (nutmeg liver): microscopic pattern: 1 –
– a nutmeg. initial stage; 2 – advanced stage with atrophy
of pericentrolobular hepatocytes (hematoxy-
due to alternation of some small, punc- lin–eosin stain; ×70).
tiform, dark red foci (centrolobular areas
of hepatic lobules) with other foci of a ighboring portions of sinusoidal capilla-
brown–yellow color (peripheral areas of
ries. However, the stasis does not extend

the lobules). to the periphery of lobules, due to the
This variegated aspect of the stasis speed and pressure of blood, which is hi-
liver is determined by the blood circula- gher in peripheral areas of the sinusoids
tion features and angioarchitectonics of where the arterial capillaries penetrate
the organ. Microscopically, the central from the hepatic artery system (at the
veins of the hepatic lobules and adja- border between the external third and
cent portions of sinusoidal capillaries the medium third of the hepatic lobu-
are dilated, full of blood, and there are les). Such being the case, the center of
diapedetic hemorrhages in the center of the hepatic lobule is hyperemiated, but
the lobules (”blood lakes”), the hepato- the periphery is not, and this is what de-
cytes are atrophied, the central porti- termines the variegated (“nutmeg-like”)
ons of hepatic trabeculae are thin (these aspect of the stasis liver. The mechanism
pericentrolobular areas have a dark red of development of nutmeg liver is sche-
color under the microscope). There is matically illustrated in the Fig. 4–6.
a fatty dystrophy of hepatocytes in in- The stasis cirrhosis (cardiac) of the
termediary zones of the lobules (they liver develops as a result of chronic ve-
appear brown–yellow macroscopically), nous hyperemia. Frequently, it is esta-
but, in the peripheral areas, the sinu- blished in the right cardiac insufficiency
soidal capillaries and hepatocytes are (stasis in greater circulation). A similar

the section and the pulmonary poro-
sity of the parenchyma is diminished
(Fig. 4–7 a).
The increased consistency of the
lungs is a consequence of excessive pro-
liferation of the connective tissue in the
alveolar walls; their coloration derives
from the accumulation of hemosiderin
pigment. The decreased porosity is due
to the thickening of alveolar septa, beca-
use of hyperemia of vessels and sclerosis.
Fig. 4–6. The scheme of blood circulation in he- Microscopically (Fig. 4–7 b), the interal-
patic lobule. veolar septa are thickened, sclerosed, the
veins and capillaries are dilated, hype-
pattern can develop in hepatic veins remiated, with thickened walls. The al-
thrombosis (the Budd–Chiari syndro- veolar spaces contain agglomerations of
me). phagocyte cells (alveolar macrophages),
The lungs in chronic venous stasis filled with hemosiderin granules (side-
are enlarged in volume and mass, has roblasts and siderophages); some alveoli
a dense consistency, a brown color on contain edema fluid, whole erythrocytes

b
Fig. 4–7 a. Chronic venous hyperemia of the Fig. 4–7 b. Chronic venous hyperemia of the
lung (brown induration of the lung): macrosco- lung (brown induration of the lung): microsco-
pic aspect. pic aspect (hematoxylin–eosin stain; ×70).
or parts of disintegrated erythrocytes. called “cardiac cells”. The presence of
The lesions are more emphasized in hemosiderin pigment gives the sputum
lower posterior areas of the lungs. rust–colored nuance. Diapedetic hemor-
Stasis hyperemia of the lungs occurs rhages, hemosiderosis and proliferation
especially in the left cardiac insufficien- of connective tissue are related with ve-
cy, first of all in mitral stenosis (hence nous tissular hypoxia, which determines
the name “cardiac lung”). Macrophages the increasing of vascular permeability
with hemosiderin granules in cytoplasm and of the synthetic activity of fibro-
can be found in the sputum of the pa- blasts of the alveolar septa.
tients with cardiac insufficiency and are

4.1.2.2. LOCALIZED VENOUS HYPEREMIA

Localized venous hyperemia is ob- nic in case of portal hypertension in he-
served in the case of disorder of venous patic cirrhosis; b) liver venous hyperemia
blood reflux from one organ or part of the with development of nutmeg liver as a
body, due to the occlusion of the lumen of result of inflammation and thrombosis of
the veins by a thrombus or embolus, veins hepatic veins in the Budd–Chiari syndro-
compression from exterior by tumors or me; c) kidneys venous hyperemia with
adherences etc. Examples: a) acute venous their stasis induration, in cases of renal
hyperemia of the abdominal cavity organs veins thrombosis; d) venous stasis of limbs
in thrombosis of the portal vein, or chro- in varicose disease and thrombophlebitis.
4.2. ISCHEMIA
The ischemia is the reduction or minutes. The organs with high
suppression of the arterial blood flow glycolytic capacity may survive the
in a tissue, organ or a part of an organ. reduction of oxygen quantity and
Thrombosis, embolism and angiospasm oxidative phosphorylation (ex. the
are the most frequent causes of this phe- liver), rather than the organs with
nomenon. Macroscopically, the ischemi- a reduced potential of anaerobic
ated organ is reduced in size, has a low glycolysis (ex. the brain).
temperature and a pale color. The effects h) the state of tissular metabolism;
of ischemia depend on many factors, of i) functional state of the organ at the
which the main are: moment of ischemia onset (a state
a) rapidity of occlusion onset (sudden of effort or pause).
or slow, gradual); Dystrophic and necrotic lesions ap-
b) degree of obstruction (partial or pear in acute ischemia, they being rela-
complete); ted to depriving the tissue of oxygen and
c) level of obstruction (major or mi- nutritive substances and accumulation of

nor ramifications of arteries); some metabolic products. These lesions
d) specific features of the causative are preceded by certain histochemical
agent (spasm, thrombus, embolus); and ultrastructural changes: disappea-
e) the state of collateral circulation; rance of glycogen from the ischemiated
f ) duration of obstruction (ischemia); tissue, diminution (disappearance) of ac-
g) sensitivity of tissue to insufficien- tivity of the oxidoreductive enzymes, tu-
cy or lack of oxygen. For instance, mefaction and destruction of mitochon-
the skeletal muscle can recover in dria. A prolonged obstructive ischemia
2–3 hours after the ischemia, whi- may induce ischemic necrosis – infarc-
le the cardiac muscle dies in 20–30 tion.
4.2.1. VARIANTS OF ISCHEMIA
1) Angiospastic – caused by the spasm 2) By obturation – caused by thrombosis,

of the artery, under the action of va- embolism, inflammation of arterial
rious vasoconstrictive factors (in ar- wall, proliferation of connective tissue
terial hypertension, atherosclerosis, (in artery atherosclerosis, obliterative
obliterative endarteritis). endarteritis, productive vasculitis).

3) By compression – caused by compre- portant amount of blood in an area,
ssion of the artery from exterior, in which has previously been ischemia-
tumors, accumulations of fluid, liga- ted (for example, ischemia of the bra-
tures, exostoses. in, after a rapid elimination of the as-
4) By blood redistribution – in cases cites fluid from the abdominal cavity,
when there is a penetration of an im- in patients with hepatic cirrhosis).
The infarction is the necrosis of an
4.3. INFARCTION
organ’s portion or of a whole organ cau- rance of glycogen from sarcoplasm

sed by the cessation of blood irrigation, of cardiomyocytes is one of the
as a consequence of ischemia (vascular early signs of myocardial ischemia;
or ischemic necrosis). ²² determination of the activity of
The direct causes of infarction can be: oxidoreductive enzymes (succina-
a) a prolonged spasm; te dehydrogenase, NAD-diapho-
b) thrombosis; rase); the reaction product – gra-
c) embolism; nules of formazan are colored in
d) functional overstrain of the organ blue–violet; the reaction mecha-
in conditions of its insufficient nism consists in reduction of te-
blood irrigation; an imbalance trazolium salts under the action
appears between arterial blood
flow and the need of the organ in
oxygen.
There are two successive stages in
evolution of infarction: ischemic (prene-
crotic) and necrotic. In order to diagno- M

se the early ischemic lesions (the ische-
mic stage of infarction), histochemical,
electron microscopic methods are used,
as well as luminescence microscopy, for GL
example: a
1) Electron microscopy – observes
the tumefaction and destruction of mi-
tochondria, reduction and disappearan-
ce of glycogen from the sarcoplasm of N M
cardiomyocytes (Fig. 4-8 b); lesions start
in 10–20 minutes, developing up to the
rupture of mitochondrial membranes in
1–2 hours after ischemia onset.
2) Histochemical methods:
²² histochemical identification of M
glycogen (PAS-reaction or Best b
reaction with carmine) – glycogen Fig. 4–8 a, b. Ischemia stage of myocardial
granules are colored in red (after infarction (electron microscopy; ×10000): a –
treated with amylase, the glycogen normal cell; b – ischemiated cell; N – nucleus,
disappears), the rapid disappea- M – mitochondria; Gl – glycogen.

of the succinate dehydrogenase. Photochemical fluorochroming

The ischemiated areas register a (treatment of samples with short wave
diminution and disappearance of UV rays); the luminescent intensity of
glycogen from the cells (starting ischemic foci is greater comparatively
in 5–15 minutes after the onset of with intact areas. The changes of sar-
ischemia), a decreasing and abo- coplasm fluorescence of cardiomyocytes
lition of oxidoreductive enzymes are due to physicochemical disturbances
activity (Fig. 4 – 9). of myofibrillar proteins, first of all of the
myosin in conditions of ischemia. These
changes determine a more intense fixati-
on of acridine orange by the myosin and
the increase of luminescence intensity of
the ischemic cells.
The length of ischemic stage of in-
farction is approximately 18–24 hours.
The necrotic stage develops after this
interval, characterized by autolysis of
mortified tissue and all macro- and mi-
croscopical signs of necrosis, the area of
Fig. 4–9. Recent myocardial infarction: a his- infarction becoming visible macroscopi-
totopographic reaction with nitroblue tetrazo- cally (Fig. 4– 11 a, 4–11 b).
lium for identification of succinate dehydroge-
nase, diminution (disappearance) of enzymatic
activity in the ischemic area.
The reaction to SDH–ase and other
oxydoreductive enzymes disappear in 12
hours from the onset of ischemia.
3) Luminescent microscopy:
²² staining of specimens with acridi-
ne orange – ischemic areas have a
luminescence of yellow–greenish
color, more intense than the intact
tissue (Fig. 4 – 10). a
b
Fig. 4–11 a, b. Myocardial infarction, necrotic
Fig. 4–10. Ischemic stage of myocardial infarcti- stage; a) microscopic pattern; karyolysis of car-
on, luminescent microscopy with acridine oran- diomyocytes (hematoxylin–eosin stain; ×110);
ge staining; ×70). b) macroscopic aspect.

According to exterior aspect (color) peripheral area of infarction, followed by
and mechanism of formation, there are their dilatation, hyperemia and diapede-
3 variants of infarction: tic hemorrhages; it happens in myocar-
²² white (ischemic); dium, kidneys.
²² red (hemorrhagic); According to geometric shape, in-
²² white with a red border (ischemic farctions can have a triangular (conical)
with hemorrhagic belt). shape – in the organs with a magistral
White infarction (ischemic) occurs type of vascularization (in the spleen,
in cases of collateral circulation insuffi- lungs, kidneys), and an irregular shape
ciency. It happens most frequently in the - in cases of a rich anastomotic circula-
spleen. tion of the organ (in myocardium, brain,
Red infarction (hemorrhagic) is re- intestine).
gistered in cases of double vasculariza- According to necrosis type, infarc-
tion of the organ and venous stasis; it tions may belong to the dry (coagula-
happens in the lungs, intestine. tive) type of necrosis – in myocardium,
White infarction with red border spleen, kidneys and to the liquefactive
(ischemic with hemorrhagic belt) is re- (colliquative) type of necrosis – in the
lated to the spasm of the vessels from brain, intestine.
4.3.1. MORPHOLOGIC CHARACTERISTICS OF INFARCTIONS

OF DIFFERENT ORGANS
Lienal infarction. The infarction In those areas in which the infarc-
area is well delimited, of a triangular tion extends up to the surface of the
(conical) shape, with the tip of it pointed spleen, the capsule is rugged, covered
towards the hilum of the organ and the with deposits of fibrin (reactive fibrino-
base - towards the capsule. It has a white us perisplenitis), causing pains in the left

color and a dense consistency, because it hypochondrium. The most frequent ca-
is a coagulative necrosis. (Fig. 4–12). use of the splenic infarction is the lienal
artery thrombosis or embolism. It occurs
also in verrucous rheumatismal endocar-
ditis, infective endocarditis, leukemias,
ischemic cardiopathy, arterial hyperten-
sion etc. The conical shape and white
color are determined by the magistral
type of vascularisation of the spleen
and by the poor collateral circulation,
which excludes the possibility of blood
penetration in infarction area through
collaterals. There is an infiltration with
polymorphonucleated leukocytes at the
periphery of infarction, as a manifestati-
on of demarcation inflammation delimi-
ting the necrosed area. It is determined
by the harmful action of toxic substances
Fig. 4–12. White infarction (ischemic) of the released from necrotic masses.
spleen and post infarction scar.

Usually, the spleen infarction has a

benign evolution, but in some cases a
rupture of the spleen may happen, with
hemorrhage in abdominal cavity, ab-
scess, and total necrosis of the organ.
The most frequent consequence is orga-
nization and cicatrization of infarction
and deformation of the spleen. Perifocal
inflammation of the capsule often leads
to the appearance of adherences betwe-
en the spleen capsule and diaphragm,
parietal peritoneum, intestinal loops.
The red infarction with massive he-
morrhages in the necrosed tissue de-
velops less frequently in the spleen. It
a occurs in thrombosis or compression of
lienal artery on background of venous
stasis of the spleen (venous hemorrhagic
infarction).
Renal infarction. A well delimited,
extended area of triangular shape is ob-
served in kidneys, with the tip oriented
to the renal pelvis and the base - to the
capsule, of white–yellowish color, surro-
unded by red belt (white infarction with
hemorrhagic belt), an increased consis-
b tency (Fig. 4–13 a and 4 – 13 b).
Fibrinous deposits can be found on
the surface of the capsule. Usually, the

necrotic process is related to both layers
of the renal parenchyma. As a result of
the hemorrhagic rim, the renal infarcti-
on is clinically manifested by hematuria
and the inflammation of the capsule
determines the appearance of pains in
lumbar region. The most frequent cau-
ses of renal infarction are the renal artery
thromboembolism or thrombosis. It can
be observed in rheumatic and infecti-
ve endocarditis, atherosclerosis, arterial
hypertension, ischemic cardiomyopathy
etc. The red infarction (venous) develops
rarely in kidneys – in cases of renal vein
c thrombosis. The most frequent con-
sequence of renal infarction is cicatriza-
Fig. 4–13 a, b, c. Renal infarction: a – macrosco-
tion (organization) (Fig. 4 – 13 c).
pic aspect; b – microscopic pattern (karyolysis
Pulmonary infarction. The infarc-
of all the cellular elements) (hematoxylin–eosin
tion area has a conical shape, the base
stain; ×110); c – post infarction scar.

towards pleura, a dark red color, hard septums are thickened, edematous, with
consistency, non-aerated, full of blood; dilated and hyperemic capillaries, with
fibrinous deposits are observed on the agglomerations of erythrocytes in alve-
pleura (Fig. 4–14 a). Microscopically oli. The cause of pulmonary infarction
(Fig. 4–14 b), the alveoli are filled with is obstruction of a branch of pulmonary
extravasated erythrocytes; the alveolar artery by thrombosis or embolism (with
a starting point from peripheral venous
a b 1 2
Fig. 4–14 a, b. Pulmonary hemorrhagic infarct: a - macroscopic aspect, b - microscopic pattern (1
– recent stage, 2 - advanced stage with karyolysis of alveolar septa and hemolysis of erythrocytes);
(hematoxylin–eosin stain; ×110).
system, particularly of the lower limbs nifested through hemoptysis (the pre-
veins). The hemorrhagic character of sence of blood in sputum) and pleural
infarction is determined first of all by friction (frottage) at auscultation.
the double circulation of pulmonary tis- The usual consequence of pulmonary
sue: from the pulmonary artery (small infarction is cicatrization. Possible com-
circulation) and bronchial artery (great plications are: post infarct pneumonia,
circulation); there are multiple anasto- pulmonary abscess, pleural empyema,

moses between these arteries, which do pneumothorax, pulmonary gangrene.
not function in physiological conditions. The white infarction (ischemic) occurs
The obstruction of pulmonary arteries is rarely in lungs – in cases of obstruction
followed by the reflex opening of ana- of bronchial artery through sclerosis and
stomoses and penetration of the blood obliteration.
under pressure from the great circulation Cerebral infarction. It settles more
system (bronchial artery) into the ische- frequently in subcortical nuclei and the
miated area. This induces the rupture of occipital zone. Necrotic foci are soft, of
the walls of pulmonary capillaries and white–grayish color (colliquation necro-
venules and blood overflowing the in- sis) and irregular shape. These changes
farction area (interalveolar septums and are called encephalomacia or white sof-
alveoli spaces). The second factor de- tening. Microscopically, one observes a
termining the hemorrhagic character of rarefaction of cerebral tissue, gradual di-
pulmonary infarction is the venous sta- sappearance of nervous cells, infiltration
sis, because it encourages the retrograde of affected area with numerous mono-
circulation of blood through the veins cytic and microglial macrophages (gra-
and flooding the ischemiated zone. Ve- nulous bodies), hyperplasia of astrocytes
nous stasis takes place in the left cardiac (Fig. 4–15).
insufficiency, mainly in mitral stenosis. It is more frequently seen in athe-
Clinically, pulmonary infarction is ma- rosclerosis of cerebral arteries or ma-

gistral arteries of the head (carotid and

vertebral) and in arterial hypertensi-
on, the direct causes being the spasm,
thrombosis or the embolism of arteries.
Fig. 4–15. Ischemic cerebral infarction, necrosis

and disintegration focus of cerebral tissue with
a large number of granulous bodies (hemato-
It is also observed in cases of intracar-
diac thrombosis (for example, in acute b
transmural myocardial infarction, cardi-
ac aneurysm) and rheumatic verrucous Fig. 4–16 a, b. Postinfarction cerebral cyst: a –
endocarditis. Clinically, it is manifested microscopic pattern (hematoxylin–eosin stain;
by psychic or neurological distrurban- ×110); b – macroscopic aspect.
ces, depending on localization of necro- sistent myocardium, there appears the
tic process, for example, the affection of demarcation inflammation with a more
subcortical nuclei and lesion of conduc- or less intensive leukocyte reaction, due
tion ways leads to paralysis. As a result to which there is a resorption of necro-
of the ischemic cerebral infarction of tic masses and a gradual substitution of

smaller dimensions, a connective glial infarcted zone with connective tissue. It
scar is formed, and the extended softe- is more frequently localized in the ante-
ning suffers a cystic transformation (Fig. rior wall of the left ventricle. There may
4–16 a and 4–16 b). be an anterior isolated or anteroseptal
Myocardial infarction. It is the infarction, with involvement of the in-
most frequent and important form of terventricular septum. Depending on
ischemic cardiopathy. Etiologically and the extension of the necrosis zone into
pathogenetically, it is related to athe- the thickness of the ventricular wall, we
rosclerosis of the coronary arteries and distinguish subendocardial, intramural,
arterial hypertension. In the majority of subepicardial and transmural infarc-
cases, according to macroscopical aspect, tion. The transmural infarction may
it is a white infarction with a red border, complicate with fibrinous pericarditis
the central necrosis zone having a whi- and/or thromboendocarditis. The most
te–yellowish color, while the periphery frequent consequence of myocardial in-
is red. The consistency of the necrosis farction is organization (cicatrization) of
zone becomes flaccid, the process of sof- necrosis zone (postinfarction macrofocal
tening being called myomalacia. A red cardiosclerosis).
myocardial hemorrhagic infarction is re- The clinical importance and the
gistered in 1–1,5 % of cases. At the limit infarction effects depend on its loca-
between the necrosis zone and the per- lization and extension. In some cases,

infarction may unfold asymptomatically, a. autolysis, resorption of necrotic
without functional significance, but in masses and restoration of the pre-
case of lesion of some organs of vital existent tissue;
importance, it may result in severe com- b. organization (cicatrization);
plications, including a lethal outcome c. encapsulation;
(cerebral, myocardial infarction). The d. petrification (calcification);
general phenomena in case of infarction e. formation of cysts (cystic trans-
are manifested by fever and leucocytosis. formation);
Possible consequences of infarc- f. hemosiderosis;
tion of different localization are the g. purulent lysis (suppuration).
following:
4.4. HEMORRHAGE
Hemorrhage is the blood exiting frequently by traumas or surgical
from the vessels lumen or from the cavi- interventions, but it may also be
ties of the heart. observed in some diseases with the
According to the origin, hemorrha- increasing of vascular wall perme-
ges are subdivided into: ability (ex., in avitaminosis C) or
²² cardiac – caused by a penetrant thrombocytopathies (ex., in idio-
wound of the thorax or a rupture pathic thrombocytopenic purple);
of the ventricular wall, as a result ²² venous – it occurs frequently in tra-
of myocardial infarction or cardiac umas and surgical interventions.
aneurysm; Hemorrhage may be external – the
²² arterial – as a rule, a consequence of blood drains out of the organism, and
a trauma or a rupture of aneurysm; internal – when blood accumulates in
²² capillary – conditioned more tissues, organs or preexistent cavities.
4.4.1. MECHANISMS OF HEMORRHAGES

1) by vessels rupture (per rhexin) – varicosities, traumatisms, leukemias
is observed in arterial hypertension, ath- (Fig. 4–17 and 4–18).
erosclerosis, arterial aneurysm, cardiac 2) by vascular wall erosion (per di-
aneurysm, myocardial infarction, venous abrosis) – it occurs in ulcer disease, ty-
Fig. 4–17. Rupture of the spleen. Fig. 4–18. Cerebral parenchymatous hemorr-
hage (hematoma).

phoid fever, dysentery, tuberculosis, 3) by diapedesis (per diapedesis) –

abscess, malignant tumors (cancer, sar- caused by increase of permeability of
coma), tubal pregnancy (Fig. 4–19 a and vessels. It is observed in tissue hypoxia
4–19 b); (ex: cardiovascular insufficiency, respira-
a b
Fig. 4–19 a, b. Chronic gastric ulcer, erosion of an artery on the bottom of ulcer: a) macroscopic
aspect; b) microscopic pattern (hematoxylin–eosin stain; ×110);
tory, anemias), avitaminosis C, arterial

hypertension, infectious diseases (ex: in-
fluenza, smallpox, anthrax, septicemia),
leukoses, systemic vasculitis (Fig. 4–20).
Fig. 4–20. Cerebral diapedetic perivascular he-

morrhage (hematoxylin–eosin stain; ×110).
4.4.2. TERMINOLOGY OF HEMORRHAGES

(A) External hemorrhages: gastric ulcer, erosive gastritis, eso-
1) Epistaxis (rhinorrhagia) – noseble- phageal/gastric varicosities in hepa-
ed; it occurs in traumatisms, tumors, tic cirrhosis, Mallory–Weiss syndro-
arterial hypertension, hemophilia, me, esophageal and gastric cancer.
sinusitis. The emetic masses may contain
2) Hemoptysis – oral expulsion of fresh or digested blood with a “coffee
blood, caused by a bronchopulmo- ground ” aspect (blood clots conditi-
nary hemorrhage; it occurs in lung on this characteristic aspect); the co-
cancer, tuberculosis, abscess, bron- lor is determined by the hydrochlo-
chiectases. ric hematin pigment, produced from
3) Hematemesis – vomiting blood, a hemoglobin, under the action of the
sign of upper gastrointestinal he- hydrochloric acid from gastric juice;
morrhage, localized higher than the the blood gets a “coffee ground” as-
ligament of Treitz (the duodeno-je- pect after staying in the stomach for
junal flexure), more frequently from some hours.
stomach or esophagus. It occurs in 4) Melena – elimination of a stool

with black, digested, tarry blood, of as macroscopic, visible to the naked
pasty consistency; it is observed in eye, and microscopic, revealed only
upper gastrointestinal hemorrhages at the microscopic examination of
(ex: in those listed above). The black the urinary sediment. It is a sign of
color is determined by the appearan- the urinary system pathology, for
ce of iron sulphite, as a result of an example, of glomerulonephritis, pye-
interaction between the hemoglobin lonephritis, urinary calculi, cystitis,
and the hydrogen sulphide from the renal or bladder tumors.
intestine. Melena appears in severe 11) Otorrhagia – hemorrhage from the
blood losses, of at least 60–80 ml, ears.
from upper digestive segments, at an 12) Stomatorrhagia – hemorrhage from
intestinal transit of at least 8 hours. buccal mucosa.
5) Hematochezia – rectal bleeding,
(B) Hemorrhages in serous cavities
presence of fresh, red, indigested
and cavitary organs (the term is for-
blood in feces. Usually, the localizati-
med by the prefix hemo - or hemato
on of the hemorrhage is in the lower
- and the name of the respective ana-
gastrointestinal segments, lower
tomic portion):
than the ligament of Treitz, for ex: in
1) Hemopericardium – hemorrhage
intestinal polyposis, ulcerative colitis,
in pericardial sac.
Crohn’s disease, intestinal cancer and
2) Hemothorax – hemorrhage in ple-
diverticulosis, hemorrhoids, it may
ural cavity;
also be in massive upper gastrointes-
3) Hemoperitoneum – accumulation
tinal hemorrhage, with rapid transit
of blood in peritoneal cavity;
through the intestines.
4) Hemarthrosis – hemorrhage in the
6) Rectorrhagia – rectal bleeding, a
cavity of a joint.
generic term indicating a hemorrha-
5) Hematocele – hemorrhage in the

ge from any segment of the gastroin-
tunica vaginalis of the testicle or in
testinal tract.
scrotal tissues;
7) Metrorrhagia – intermenstrual
6) Hemosalpinx – hemorrhage in the
uterine bleeding, having no relation
lumen of the Fallopian tube.
with the menstrual cycle. It is obser-
7) Hemocholecyst – hemorrhage in
ved in extrauterine pregnancy, abor-
the cavity of the gallbladder.
tion, polyposis, glandular hyperplasia
8) Hemoamnion – hemorrhage in
of endometrium, benign and malig-
amniotic fluid through the rupture
nant uterine tumors.
of umbilical cord vessels.
8) Menorrhagia – heavy menstrual
9) Hematometra – blood accumulati-
bleeding (abundant prolonged men-
on in uterine cavity.
struation) in different diseases of the
female genital tract (including those (C) Variants of hemorrhages according
mentioned above). to size and specific features:
9) Menometrorrhagia – menstrual 1) Petechia – punctiform hemorrhage
bleeding that does not stop in several of less than 1mm, usually of capillary
days after the onset. origin.
10) Hematuria – blood elimination 2) Ecchymosis – hemorrhages in the
with the urine. It may be classified skin, mucous or serous membranes,

manifest by spots of thumb-nail or morrhages in the skin and mucous

a little larger, which are not promi- membranes, in the form of petechiae
nent; they are of capillary origin or and ecchymoses. It can be observed
from small vessels. in thrombocytopenia, infectious di-
3) Hemorrhagic suffusion – flat he- seases (septicemia), intoxications,
morrhage under a covering layer systemic vasculitis, DIC syndrome.
(skin, mucous, serous membranes),
(D) Morphologic variants of interstiti-
which may reach a large size.
al (in tissues) hemorrhages:
4) Apoplexy – acute massive hemor-
²² hemorrhagic infiltration – in-
rhage into an organ, with a more
terstitial hemorrhage, when the
or less complete suspension of the
blood penetrates between tissular
organ’s functions (cerebral, ovarian,
elements that maintain the struc-
suprarenal apoplexy).
tural integrity;
5) Cephalhematoma – cranial subpe-
²² hematoma – circumscribed blood
riosteal hematoma in newborn, as a
accumulation in a tissue and for-
result of obstetrical traumatism; it
mation of a cavity, as a result of
may be external and internal (betwe-
compression and destruction of
en dura mater and periosteum).
the adjacent tissue; the blood may
6) Purpura – syndrome characterized
be fluid or coagulated.
by appearance of some multiple he-
4.4.3. THE MOST FREQUENT CONSEQUENCES OF INTERNAL HEMORRHAGES
1) blood resorption; 4) formation of cystic cavities (ex. in

2) organization; the brain);
3) encapsulation (encystation); 5) suppuration.
4.5. PLASMORRHAGIA
Plasmorrhagia is the escape of plas-

ma from the vascular bed with imbibiti-
ons of the vessels walls and surrounding
tissue (Fig. 4 – 21).
It is determined by increase of vas-
cular permeability and is frequently
observed in arterial hypertension and
atherosclerosis, cardiac insufficiency, in-
fectious diseases, diabetes mellitus. Plas-
matic infiltration leads to subsequent
hyalinosis of arterial walls. Fig. 4–21. Plasmatic infiltration of cerebral ar-
teriole (hematoxylin–eosin stain; ×110).

ESSENTIAL TERMS
on the subject “DISTURBANCES OF BLOOD
CIRCULATION: hyperemia, ischemia, infarction, hemorrhage”
anasarca hematuria hydropsy

apoplexy hemoamnion hydrothorax
ascites hemocholecyst hyperemia
Budd–Chiari syndrome hemopericardium infarction
cephalhematoma hemoperitoneum melena
cyanosis hemoptysis menorrhagia
cyanotic induration hemorrhage nutmeg liver
ecchymosis hemorrhage per diabrosis metrorrhagia
encephalomalacia hemorrhage per diapedesis myomalacia
epistaxis hemorrhage per rhexin otorrhagia
hemarthrosis hemorrhagic infiltration petechia
hematemesis hemorrhagic suffusion plasmorrhagia
hematocele hemosalpinx purpura
hematochezia hemothorax rectorrhagia
hematoma hydropericardium stasis
hematometra hydroperitoneum stomatorrhagia
TESTS
on the subject “DISTURBANCES OF BLOOD
CIRCULATION: hyperemia, ischemia, infarction, hemorrhage”

SET I.
Multiple-choice questions with one cor- e) chronic venous hyperemia of
rect answer. kidneys.
1. Which sign is characteristic for the left 3. Which of the pathological processes listed
cardiac insuff iciency: below usually associate with mitral in-
a) hepatomegaly; suff iciency:
b) splenomegaly; a) thrombosis of pulmonary veins;
c) ascites; b) thromboembolism of pulmo-
d) inferior limbs edema; nary artery;
e) dyspnea. c) pulmonary edema;
2. All the listed clinical signs are characte- d) fibrinous pleuritis;
ristic for the right cardiac insuff iciency, e) pericardium tamponade.
except: 4. Which of the listed signs is characteris-
a) pulmonary edema; tic for the infarction caused by venous
b) ascites; occlusion:
c) nutmeg liver; a) it can be white or red;
d) chronic venous hyperemia of b) it occurs only in the lungs;
the spleen; c) it is always red (hemorrhagic);

d) it is always white (ischemic); b) liquefied;

e) it is white with hemorrhagic c) bilateral;
border. d) septic;
5. As a rule, the pulmonary infarction is: e) hemorrhagic.
a) white;
SET II.
Multiple-choice questions with 2, 3 or monary tissue;

more correct answers. b) diffuse pneumosclerosis, more
1. Which of the listed diseases may cause evident in posterior inferior
generalized venous hyperemia: areas;
a) portal vein thrombosis; c) fibrinous pleuritis;
b) decompensated cardiac valvu- d) pulmonary emphysema;
lopathies; e) sclerosis of pulmonary blood
c) disturbances of rhythm and car- vessels.
diac conduction; 4. Which of the listed pathological processes
d) thrombosis of hepatic veins; develop as a result of stasis in the infe-
e) thrombosis of femoral artery; rior vena cava:
f ) myocardial infarction. a) nutmeg liver;
2. Which of the morphological lesions listed b) cyanotic induration of the spleen;
below are characteristic for the chronic c) edema in lower extremities;
venous hyperemia of the organs: d) ascites;
a) increased size; e) pulmonary edema.
b) decreased size; 5. Which of the macroscopic changes listed
c) flaccid consistency; below are observed in the ischemia of
d) dense consistency; organs:
e) smooth, extended capsule; a) enlarged size;

f ) shriveled, wrinkled capsule; b) flaccid consistency;
e) red–violaceous (cyanotic) color; c) dense consistency;
h) bright red color. d) smooth, extended capsule;
3. Which of the morphological lesions listed e) shriveled, wrinkled capsule;
below are observed in chronic venous f ) pale color;
hyperemia of the lungs: g) bright red color;
a) diffuse hemosiderosis of pul- h) increased local temperature.
SET III.
Classification tests include 2–4 subjects b) brown induration of the lungs;

and a series of answers. Indicate the correct c) hydropsy of the serous cavities;
answers for each subject separately. d) subcutaneous edemas in lower
1. Which of the pathological processes listed extremities;
below are characteristic for: e) pulmonary edema;
I – left cardiac insufficiency; f ) cyanotic induration of kidneys;
II – right cardiac insufficiency; g) stasis induration of spleen.
a) nutmeg liver;

2. Which of the enumerated etiological fac- I – ischemic infarction;
tors may cause: II – hemorrhagic infarction;
I – brown induration of the lungs; III – ischemic infarction with he-
II – nutmeg liver; morrhagic border;
a) mitral stenosis ; a) the spleen;
b) insufficiency of the mitral valve; b) the kidneys;
c) tricuspid valve insufficiency; c) the myocardium;
d) thrombosis of pulmonary veins; d) the lungs;
e) stenosis of pulmonary artery; e) the brain;
f ) thrombosis of hepatic veins; f ) the intestine.
g) stenosis of aorta; 5. Which of the listed pathogenetic factors
h) obliteration of pericardial ca- may determine the appearance of:
vity. I – the white infarction;
3. Which of the pathological processes may II – the red infarction;
develop in case of stasis: a) magistral type of the organ’s
I – in the portal vein system; vascularization;
II – in the hepatic veins system; b) venous stasis;
a) nutmeg liver; c) double vascularization of the
b) ascites; organ;
c) stasis induration of spleen; d) insufficiency of collaterals;
d) congestive enterocolonopathy; e) diffuse type of vascularization
e) collateral hyperemia of esopha- of the organ with a rich ana-
geal veins. stomotic circulation.
4. In which of the listed organs one obser-
ves more frequently:

Daily practice cases are presented Questions:

with clinical and morphological data A) What pathological process developed in
from clinical histories and/or from necro- the patient’s liver:
psy protocols. Each subject includes simple a) fatty liver;
or multiple-answer questions, with 1, 2 b) cardiac liver;
or more correct answers. c) nutmeg liver;
1. In a patient after rheumatic peri- d) goose liver;
carditis, adherences between the sheets e) amyloid liver.
of the pericardium were formed and a B) What pathological process may develop
complete obliteration (closing) of the pe- in the liver during the progress of car-
ricardial sac occurred. Later, signs of cardiac insuff iciency:
diovascular insufficiency with dyspnea on a) complete recovery;
effort appeared, as well as edemas at the b) subtotal necrosis of the liver;
legs level, sensations of heaviness in the c) cardiac cirrhosis;
right costal part of the body; on palpa- d) chronic hepatitis;
tion, the liver was enlarged, painful, the e) biliary stasis.
anterior margin was rounded. 2. A patient suffered from mitral ste-

nosis of rheumatic origin. Clinically, he b) myomalacia;

presented dyspnea, cyanosis, edemas of the c) cardiac aneurysm;
lower extremities, enlarged and painful li- d) cicatrization;
ver, and cough with sputum of a rust color. e) calcinosis.
Questions: 4. A patient with post infarction
A) How can the rust color of the patient’s cardiosclerosis (old myocardial infarcti-
sputum be explained: on) died due to cardiac insufficiency. At
a) presence of hemosiderin; necropsy, on the background of chronic
b) mucus; congestive hyperemia, a non-aerated,
c) unchanged erythrocytes; dark–red area of dense consistency was
d) presence of eosinophils; revealed, being situated in the subpleural
e) coal dust. region of the right lung.
B) Which of the listed cells appear in the Questions:
sputum of patients with left cardiac in- A) What pathological process developed in
suff iciency: this patient’s right lung:
a) giant cells; a) hematoma;
b) cardiac cells; b) cancer;
c) atypical cells; c) abscess;
d) foreign body cells; d) pulmonary hemorrhage;
e) Langhans cells. e) hemorrhagic infarction.
C) What kind of acute pulmonary compli- B) What kind of changes may appear on
cation may occur in this patient: the visceral pleura:
a) brown induration; a) pleural empyema;
b) pneumosclerosis; b) pleural mesothelioma;
c) status asthmaticus; c) fibrinous pleuritis;
d) alveolar edema; d) hydrothorax;
e) emphysema. e) pneumothorax.
3. A patient with the clinical diagno- 5. A patient, who suffered from in-
sis of acute myocardial infarction died fectious endocarditis affecting the aor-
due to ventricular fibrillation. At netic valve, suddenly presented signs of
cropsy, a focus of white–yellowish color stroke with paralysis of the right part
was revealed in the anterior wall of the of the body and aphasia (loss of spee-
left ventricle of the heart. It had a flac- ch capacity). He died in 24 hours after
cid consistency and occupied the whole the cerebral edema. At necropsy, a focus
thickness of the ventricular wall. of softening of cerebral substance of ir-
Questions: regular form was revealed in the brain,
A) How does one call the myocardial in- with a diameter of ~4,5 cm, localized in
farction, which occupies the whole the subcortical area on the left.
thickness of the cardiac wall: Question:
a) circular; Which pathological process of the listed
b) subepicardial; below occurred in this patient:
c) intramural; a) cerebral hematoma;
d) transmural; b) cerebral ischemic infarction;
e) subendocardial. c) cerebral abscess;
B) Which favorable consequence is more d) cerebral tumor;
frequent in myocardial infarction: e) parenchymatous intracerebral
a) heart rupture; hemorrhage.

4. 6. THROMBOSIS
Thrombosis represents the process chambers, are called thrombi and the
of coagulation of blood in the vessel lu- ones formed postmortem or in sample
men or in the heart cavities during life- tubes – clots. The clot is formed from
time. The clots formed in the vessel in- normal constituents of the blood.
terior, in circulating blood or in the heart
4.6.1. THROMBOGENESIS MECHANISMS

The main factors encouraging the tension, vasculitis, especially phlebitis,
formation of thrombi (the so-called infections (bacterial toxins), autoimmu-
Virchow’s triad, 1845) are the following: ne disturbances (periarteritis nodosa),
a) local lesions of the vessel walls or metabolic disturbances (hyperlipidemia,
the heart; homocystinemia), infective or rheumatic
b) disorders of blood circulation; endocarditis, myocardial infarction, tra-
c) changes in blood composition with umas, surgical interventions.
its coagulation impairment. II. Changes of blood circulation.
I. Local lesions of the vessel walls The slowing down and turbulence of
or of the heart represent the dominant blood circulation has an essential role
factor in the process of thrombus for- in development of thrombi. In these
mation. The changes of the vascular en- conditions, platelets come in contact
dothelium are involved in thromboge- with the vascular wall and gather at
nesis through 2 mechanisms: the level of endothelium, starting the
1. damaged endotheliocytes produce process of thrombogenesis. The slow
and release procoagulant factors circulation encourages the formation
(for example, thromboplastin, von of platelet microaggregates, which are
Willebrand factor, inhibitors of not eliminated with the blood flow. Be-

plasminogen activator), but the sides this, the stasis reduces the inflow
synthesis of anticoagulant sub- of fresh blood that contains natural an-
stances (thrombomodulin, anti- ticoagulants. Mechanical lesion of en-
thrombin III, nitrogen monoxide dothelial cells, caused by turbulent flow
and plasminogen activators) is re- and hypoxia of endothelium in condi-
duced. tions of stagnant circulation, constitute
2. destruction and desquamation of additional favoring factors in develop-
endotheliocytes expose the un- ment of thrombi.
derlying basement membrane of As a rule, blood stasis is noticed in
the vascular wall and blood pla- dilated veins, and especially in varicose
telets adhere to these structures. veins, representing the most frequent
Binding of platelets to the vascu- cause of venous thrombosis (Fig. 4–22).
lar wall, mediated by von Wille- Turbulent blood circulation occurs
brand factor, leads to formation in arterial and cardiac aneurysms, as
of platelet aggregates and initiates well as in the atrial fibrillation, when
the formation of thrombus. the dilated heart chambers do not con-
The damage of the vascular endothe- tract regularly. According to a similar
lium and respectively the high risk of mechanism, the thrombosis of the heart
thrombosis are observed in such disea- auricles in dilated atria with stagnant
ses like atherosclerosis, arterial hyper- blood develops in patients with chronic

cardiac insufficiency (mitral stenosis,

decompensated pulmonary heart, etc.)
(Fig. 4–23 and 4–24).
Fig. 4–24. Spherical thrombus in the left atrium,

in stenosis of the left atrioventricular orifice
(mitral stenosis).
III. Changes in blood composi-
tion. In some pathological conditions,
one notices an increase of concentration
of coagulation factors and a decrease of
natural anticoagulants, which leads to a
balance disorder between pro- and anti-
Fig. 4–22 Varicose dilatation of the lower extre- coagulant factors and to hypercoagula-
mities veins. bility of blood.
The most frequent causes: throm-

bocytosis (the increase of the number of
platelets in the blood), severe trauma-
tisms, including surgical interventions,
where there is an increase of tissular
thromboplastin level as a result of tissue
lesions, malignant tumors (tumoral cells
release procoagulant substances), the
increase of blood viscosity conditioned
by the high content of macro-dispersed
proteins, for example, in malignant mye-
loma.
Other factors that increase the risk
of thromboses by hypercoagulability of
blood are an advanced age, obesity, smo-
king, oral contraceptives, etc.
In order to memorize the main ca-
Fig. 4–23. Chronic cardiac aneurysm with uses of thrombogenesis, one can use the
thrombosis. English abbreviation THROMBI:

Tissue damage – tissular damage (tra- eclampsia, early detachment of placenta
umatisms, burns, surgical interventions). etc.).
Hereditary conditions – hereditary Malignancy – malignant tumors.
anomalies of the coagulation system Blood flow disturbances – disturban-
(deficiency of antithrombin III, proteins ces of blood circulation (dilated varicose
C and S, etc.) veins, hemorrhoids, cardiac or arterial
Rest – treatment of long-term bed aneurysms, venous stasis, etc.).
rest (after surgical interventions, bone Immune mechanisms – immuno-
fractures, etc). pathological processes (disseminated lu-
Obstetrics – different conditions asso- pus erythematosus, polyarteritis nodosa,
ciated to pregnancy (normal pregnancy, antiphospholipid syndrome).
4.6.2. MORPHOGENETIC STAGES OF THROMBOSIS

The process of thrombus formation
3) agglutination of erythrocytes and
evolves in 4 stages (Fig. 4–25 a, b, c, d):
other cellular elements of the
1) aggregation of platelets;
blood;
2) transformation of fibrinogen in fi-
4) precipitation of plasmatic proteins.
brin;
En L
P
M EF
P

a En b Er
P
P
P
F En
F
P BM Er
P
P
P
c d
Fig. 4–25 a, b, c, d. Stages of thrombus formation: I (a, b) – aggregation of platelets; II (c) trans-
formation of fibrinogen in fibrin and III (d) – agglutination of erythrocytes and other cellular ele-
ments of the blood (electronic microscopy; a ×9000, b ×56000, c ×7750, d ×58000); En – endothe-
lium, P – platelets, M – mitochondria, EF – elastic fibers, Er – erythrocytes, L –lipids of lipoprotein
complexes of peripheral areas of platelets, F – fibrin filaments, BM – basement membrane.

As a result of disintegration of pla- serotonin, which causes constriction

telets, an enzyme – thrombosthenin (re- (narrowing) of vessels. Under the action
tractozyme) - is released, which has a of these substances, the retraction of the
retractile action on the thrombus, and thrombus and its densification occurs.
4. 6. 3. MORPHOLOGY OF THROMBI
Macroscopic aspects. The definiti- se of cessation of the heart activity and

ve thrombus has a dense consistency, it blood circulation, is made during au-
is dry, friable; the older the thrombus is, topsy of corpses on the necropsy table.
the more compact and harder it is (Fig. Under the action of the force of gravity,
4–26). the postmortem clots appears usually
stratified: the lower part is red, made of
erythrocytes (resembling “currant jelly”),
and the upper part is yellowish, made of
plasma (resembling “chicken fat”).
The main criteria of differentiation
of thrombus from postmortem clot are
exposed in the Table 4.1.
Table 4. 1.
Criteria of differential diagnosis
between thrombus and postmortem clot
Fig. 4–26. Parietal thrombus in the iliac vein Thrombus Postmortem clot
The surface of the thrombus is ir-  adheres to the  does not adhere
regular (goffered); the stripes (lines of vessel wall to the vessel wall
Zahn) consist of agglutinated platelets  a defect of the
and leukocytes, and are formed as a re- endothelium,  the endothelium
sult of blood waves (they resemble some- with a rugged remains intact,
how sand stripes on the river banks or on aspect, smooth, shiny
the seaside), being an obvious sign that remains after after the removal
the process of blood coagulation occur- detachment of of the clot
red during lifetime. When sectioned, the the thrombus
thrombus usually has a stratified struc-  rugged, irregular
ture, one noticing an alternation of a  smooth surface
surface
white layer of fibrin and platelets and a  opaque, dry
red layer, made of erythrocytes.  shiny, wet aspect
aspect
Differentiation criteria of throm-

 increased, dense  flaccid, elastic
consistency consistency
bus versus postmortem clot
The differential diagnosis between  does not fill the
thrombi, as an intravital process and the lumen of blood
 friable, brittle
postmortem clots, which appear becau- vessels and does
not dilate it

Most frequently, thrombi are for- served in arteries and on the valves
med in veins, particularly in the veins of the heart.
of lower extremities, hemorrhoidal, me- 2) The red thrombus (of coagulation)
senteric, portal vein, more rarely - in is composed of a fibrin meshwork
arteries (coronary, cerebral, mesenteric, with erythrocytes, thrombocytes
renal, pulmonary, aorta, etc.), especially and a small number of neutrophils
in atherosclerosis. They may also appear (Fig. 4–27). It is mostly observed in
in heart cavities, on the surface of mitral veins and is occlusive (obliterative).
and aortic valves (in infective or rheu- 3) Mixed thrombus (variegated, stra-
matic endocarditis), in the left atrium tified or striped) consists of white
(for example, in mitral stenosis) or on and red thrombus elements and
cardiac cavities walls (parietal thrombo- has a stratified structure. It is the
sis in myocardial infarction, rheumatism, most frequent variant of thrombi
cardiomyopathies etc.). and their localization may be va-
Microscopically, the thrombus is rious. A mixed thrombus consists
made up of agglutinated platelets and of three parts: head, body and tail.
fibrin filaments, among which erythro- The head of the occlusive throm-
cytes and leukocytes can be found. De- bus is oriented in veins towards
pending on the structural features and the heart (the right ventricle) and
the exterior aspect, there are 4 types of in arteries - in the opposite di-
thrombi: white, red, mixed and hyaline. rection. The parietal thrombus in
1) The white thrombus (of agglu- veins, as well as in arteries, may
tination) consists of agglomera- develop both in the direction of
tions of platelets, forming coral- the blood stream and opposite to
like structures, leukocytes and a it. The head adheres to the wall of
meshwork of fibrin filaments. It is the vessels (heart) and the body

mostly parietal and is usually ob- and the tail are free in the lumen.
4) The hyaline thrombi are usu-
ally multiple and localized in the
vessels of the microcirculatory
system. They can be seen in extre-
me conditions: shock, burn, mas-
sive tissues destruction. The hya-
line thrombi have an amorphous,
homogeneous, unstructured cha-
racter, as a result of cellular ele-
ments destruction and precipitati-
on of plasmatic proteins.
The consequences of thrombi can
be favorable and unfavorable:
I – favorable consequences:
a) resorption of thrombus;
b) aseptic autolysis (softening);
Fig. 4–27. Recent red vascular thrombus (he- c) connective organization – substi-
matoxylin–eosin stain; ×50)

tution of thrombus with granulation tis- d) vascularization and canalization

sue, which contributes to consolidation (recanalization) (Fig. 4–29); the newly-
of thrombus in the place of formation formed vessels restore partially the per-
and excludes the threat of thromboem- meability of the thrombosed vessel;
bolism occurrence (Fig. 4–28); e) calcification (petrification).
Fig. 4–28. Thrombus in course of organization Fig. 4–29. Recanalized thrombus (hemato-
(hematoxylin–eosin stain; ×70). xylin–eosin stain; ×70).
II – unfavorable consequences: organs. First of all, vein thrombosis is a

a) septic autolysis (purulent softe- source of thromboembolism of the pul-
ning); monary artery. Thrombosis of the portal
b) rupture of thrombus and its trans- vein causes portal hypertension and as-
formation into thromboembolus. cites, thrombosis of hepatic veins – the
The importance and clinical effects Budd–Chiari syndrome, thrombosis of
of thrombosis depend on localization, lienal vein – thrombophlebitic spleno-

extension and rapidity of thrombus for- megaly, thrombosis of mesenteric veins
mation. The obliterative arterial thrombi – intestine gangrene, thrombosis of ve-
may cause infarctions and gangrene. In nous sinuses of dura mater – disturban-
case of parietal arterial thrombi, which ces of cerebral circulation etc. Thrombo-
are formed slowly, the collateral circula- sis of the lower extremities veins in the
tion is included and a threat of ischemic varicose disease is frequently complica-
necrosis is avoided. The cardiac thrombi ted by thrombophlebitis. A particular
are a source of thromboembolism of the form of venous thrombosis can be seen
great circulation arteries. The thrombi in the Trousseau syndrome or migra-
from the aorta, magistral and visceral tory thrombophlebitis. This syndrome
arteries can also cause thromboembo- is frequently associated with gastric or
lism of distal arterial branches towards pancreatic cancer. It manifests itself by
the level of thrombus. Thrombosis of thrombosis of superficial veins, which
cardiac aneurysm can also have a bene- disappears spontaneously and reappears
ficial role by “strengthening” of cardiac in another place. The phenomenon can
wall and prevention of its rupture. The be explained by the appearance of relea-
effects of venous thrombi can be di- sed thromboplastin from cancerous cells
verse at different levels and in different in the blood.

4. 7. EMBOLISM
Embolism is a pathological process, (lymph) are called emboli. The emboli

characterized by circulation of some may be of exogenic or endogenic origin
particles in the cardiovascular (lympha- and, according to physical features – so-
tic) system, which do not appear in the lid (thrombi, tissue fragments, groups of
blood (lymph) in normal conditions, cells, foreign bodies, and microbial colo-
and which produce complete or par- nies), fluid (amniotic fluid, liquid fats)
tial occlusion of the blood (lymphatic) and gaseous (air, nitrogen, oxygen).
vessels. The particles spread by the blood
4. 7. 1. VARIANTS OF EMBOLISM ACCORDING TO THE COMPOSITION
a) Thromboembolism is an embo- mon trunk or of the large branches of the

lism with thrombi or fragments of de- pulmonary artery (the so-called thrombo-
tached thrombi; the starting point (the embolus alike “rider in its saddle”) leads
source) may be in veins, arteries or heart to sudden death because of pulmonary
cavities. It happens in thrombophlebites, circulation occlusion with asphyxia and
varicose disease of lower extremities ve- acute pulmonary heart (Fig. 4–30).
ins, hemorrhoids, arterial atherosclerosis,
arterial and cardiac aneurysms, infective
or rheumatic thromboendocarditis, and
myocardial infarction. It may end in in-
farctions, gangrene.
The thromboembolism of the pul-
monary artery is more important clini-
cally. The starting point of pulmonary
emboli may be the thrombosis from the

lower extremities veins, pelvic, intra-ab-
dominal veins, cava veins, and the right
cavities of the heart. Practically in 90–
95% of the cases, the source of pulmonary Fig. 4–30. Thromboembolism of the pulmonary
emboli is thrombosis of the deep veins of artery.
the lower extremities (most frequently the In some cases, a sudden death may
popliteal vena). 60–80% of emboli have occur even from relatively small emboli
small size and develop clinically asymp- through a pulmocoronary reflex with a
tomatically, due to the lysis of thrombus spasm of pulmonary artery ramification,
and compensation of circulation by the bronchi, coronary arteries and heart fai-
bronchial artery. Thromboembolism of lure. The multiple thromboemboli, which
small, terminal artery branches leads to do not occlude the pulmonary vessel lu-
installation of hemorrhagic pulmonary men, can be substituted with connective
infarction. In cases when more than 60% tissue, this leading to thickening of the
of the pulmonary vessels become simulta- wall vessels and installation of pulmo-
neously blocked by multiple small emboli nary hypertension. Thromboembolism of
or by a big embolus, there occurs an acute the pulmonary artery is one of the severe
right heart insufficiency (acute pulmo- complications in surgical interventions,
nary heart) or a cardiovascular shock and particularly in the organs of the abdomi-
sudden death. The occlusion of the com- nal and pelvic cavities.

b) Fat embolism is an embolism with or abortion, in cases of uterine atony in

particles of endogenic or exogenic fats. puerperal period, the air may penetrate
Most frequently, it occurs in fractures of the blood through the dehiscent uteri-
the tubular bones (especially of the fe- ne veins. Air embolism may appear as a
mur and tibia), rarely – in contusions of result of injections or transfusions with
the adipose tissue (subcutaneous, pelvic technical defects. An accumulation of air
at the time of birth), intravenous intro- during the small circulation vessel embo-
duction of some oleaginous substances. It lism occurs in the right compartment of
results in embolism of pulmonary capilla- the heart, blocking the blood circulation.
ries with acute asphyxia, when more than To make a diagnosis, the right cavity of
2/3 of capillaries are blocked. Small drops the heart is opened under water at autop-
of lipids, which penetrate the pulmonary sy (the water is poured into pericardial
capillary network, get into cerebral mi- sac beforehand) (Fig. 4–32); air bubbles
cro-vessels, causing small foci of necro- are eliminated eventually; the blood may
sis and pericapillary hemorrhages. About have a foamy aspect.
10% of the patients die. Fat embolism is Small quantities of air are absorbed
identified by lipid coloration at autopsy and are not dangerous, but death occurs in
(Sudan III) (Fig. 4–31). case the air volume is more than 150,0 ml.
Fig. 4–31. Fat embolism of the pulmonary blood Fig. 4–32. The test to reveal air embolism at ne-
vessels (hematoxylin–eosin stain and Sudan III; cropsy: the right ventricle is pierced with a scal-
×70). pel under water; air bubbles are eliminated in
case of a positive test.
c) Air embolism is produced when
the atmospheric air enters the venous or d) Gaseous embolism – obstruction
arterial system. It is noted in traumatisms of vessels with nitrogen bubbles. Nitro-
or surgery on the neck area, after injury gen is dissolved in the blood in physi-
of the jugular vein or superior vena cava. ological conditions, the soluble state be-
Under the action of the negative pressure ing ensured by the atmospheric pressure.
that exists in the thorax, the air is absor- It occurs in divers, caisson workers, pilots,
bed in the blood. An analogical mecha- at a rapid passage of the organism from
nism takes place in traumas or surgeries high or low atmospheric pressure to a
on thorax, lungs, heart, laparoscopy, pne- normal one. It manifests itself by occlu-
umothorax, pleural punctures. During sion of capillaries of the brain, bones,
external massage of the heart, there may soft tissues, spinal cord and other organs
be costal fractures that also present a with appearance of ischemia and necrosis
threat of air embolism. During delivery foci, punctiform hemorrhages and micro-

thrombi (the decompression or caisson The ischemic and necrotic lesions in
disease). There may be multiple and ex- tumor embolism are less important. The
tended infarctions in the organs with le- tissular embolism occurs also in ruptures
thal outcome. of cardiac valves in infective endocardi-
e) Tissular embolism (cellular) – em- tis, in cerebral and hepatic traumatisms,
bolism through isolated cells or tissue amniotic fluid embolism (squamous cells,
fragments. It is observed firstly in ma- hair (lanugo), vernix caseosa, meconium)
lignant tumors. The tumor cells infiltrate in puerperal women in cases of incom-
the walls of the blood and/or lymphatic plete detachment of placenta, embolism
vessels, proliferating extracellularly and with cerebral tissue in fetus and newborn
form secondary, metastatic tumor nod- in obstetrical trauma. Such an embolism
ules (cancer, sarcoma, melanoma – me- may also appear in bone fractures, when
tastases) (Fig. 4–33 and 4–34). the red bone marrow penetrates the
blood flow. It is most frequently noticed
Fig. 4–33. Cancer metastases in the lungs. Fig. 4–34. Cancerous embolism of the pulmonary
lymphatic vessels (hematoxylin–eosin stain; ×70).

in fractures of the ribs during the indi- organisms (colonies of microbes, fungi or
rect massage of the heart. Particles of the parasites), which get into the blood from
hematopoietic tissue get into pulmonary a septic focus. It can be seen in sepsis
arteries of small caliber together with the (septicopyemia), generating the appea-
venous blood. rance of ischemic and necrotic lesions and
f ) Microbial embolism – the embo- of purulent foci – metastatic abscesses in
lus is made of agglomerations of micro- organs (Fig. 4–35 and 4– 36).
Fig. 4–35. Embolic purulent nephritis (metasta- Fig. 4-36. Bacterial embolism of capillaries of the
tic abscesses in kidneys). renal glomeruli (hematoxylin–eosin stain; ×70).

Such complications can also be obser- including surgical ones, in catheteriza-

ved in case of some fragments of infected tion of vessels and heart, intravenous
thrombi (“sick thrombi”), for example, injecting of drugs etc. In the same con-
fragments of vegetations from the cardi- text, one can observe the embolism with
ac valve surface in infective endocarditis; cholesterol crystals, which get into the
the necrosis area is colonized by microbes arterial blood as a result of ulceration of
and transforms into abscess. Thrombi be- atherosclerotic plaques, catheterization
come a favorable environment for bacte- of aorta or surgical interventions in ar-
rial development and are easily infected.
teries. The foreign body embolism con-
The organization of the infected thrombi
ditions the appearance of ischemic and
leads to thrombophlebitis.
necrotic foci in the organs. For example,
g) Foreign body embolism – embo-
embolism with cholesterol crystals of
lism with cotton, cloth fibers, talcum or
retina arteries may cause blindness, of
starch crystals, fragments of catheters,
arterioles and renal glomeruli capillaries
needles, calcium salts, splinters, bullets
– acute renal insufficiency.
etc. It can be observed in traumatisms,
4.7.2. VARIANTS OF EMBOLISMS ACCORDING TO THE DIRECTION
OF THE EMBOLUS CIRCULATION
1) Direct (forward) embolism – the into the right compartments of
embolus circulates in the direction of the the heart and into the small cir-
blood flow (Fig. 4–37): culation vessels (in the pulmonary
²² from the great circulation veins artery and its branches);
Emb
FO PA
RL PA LL Emb
Emb
RV
LV
Emb A
RK A LK
RK Emb
IVC
IVC
Fig. 4–37. The scheme of direct (forward) em- Fig. 4–38. Paradoxical embolism scheme: Emb
bolism A – aorta, IVC – inferior vena cava, L – embolus, FO –foramen ovale, PA – pulmo-
– liver , LL and RL – left and right lung, LK and nary artery, A – aorta, IVC – inferior vena
RK – left and right kidney, PA – pulmonary ar- cava, LV and RV – left and right ventricles, RK
tery. – right kidney.

²² from the pulmonary veins, the left It can be found in congenital heart
compartments of the heart, aorta diseases: the persistence of foramen
and major arteries into the gre- ovale (interatrial communication) (Fig.
at circulation arteries (lower and 4–39), interventricular septal defect and
upper extremities arteries, celiac, arteriovenous shunts (communication)
lienal, mesenteric, renal, cerebral, especially in cases of Botallo duct per-
coronary arteries); sistence; example – the thrombus from
²² from the branches of the portal hemorrhoidal veins may reach the cere-
system into the portal vein trunk bral arteries.
and liver. 3) Retrograde embolism – the cir-
2) Paradoxical (crossed) embolism culation of embolus against the blood
– when the embolus from the big cir- flow; for example, embolism of hepatic
culation veins reaches directly the left or renal veins, when the thromboembo-
compartments of the heart and the great lus comes from the inferior vena cava at
circulation system arteries, avoiding the the moment of sudden increase of in-
small circulation system (the pulmonary traabdominal or intrathoracic pressure
capillary system) (Fig. 4–38). (during a cough access) (Fig. 4–40).
Emb
IVC

RK
RK Emb
Fig. 4–39. Congenital cardiac malformation: Fig. 4–40. Retrograde embolism scheme: Emb
interatrial septum defect. – embolus, T – thrombus, IVC – inferior vena
cava, LK and RK – left and right kidney.
4.7.3. CONSEQUENCES OF EMBOLISM

The effects and consequences of em- vascular occlusion consequences can be
bolism depend on the nature (structure), particularly dangerous in cerebral artery
spreading and localization of emboli. The embolism (ischemic infarction, white ce-
most frequent and severe effect of arterial rebral softening), coronary (myocardial
embolism is ischemia, which leads to de- infarction), and pulmonary (pulmonary
velopment of infarction or gangrene. The infarction or sudden death in pulmonary

artery thromboembolism). Air, gaseous tumors (cancer, sarcoma) is the main way
and fat emboli can resorb but if the em- of metastasis and generalization of the
bolism is massive, severe complications tumoral process (the process of transfer of
may appear. Microbial (septic) embolism some pathological elements from one place to
may generate metastatic abscesses, which, another in the organism, with the appearan-
depending on the localization, may have ce of some secondary pathologic foci distanced
a vital importance in the dissemination from the primary focus is called metastatic
and generalization of the infection. The process; the secondary focus that appears in
cellular (tissular) embolism in malignant this way is called metastasis).
4. 8. STASIS (HEMOSTASIS)
Stasis is the stopping of blood in ca- A variant of stasis is the sludging con-
pillaries and venules with a dilated lumen, dition (from the English sludge – mud),
accompanied by aggregation (sticking) of which consists in sticking of erythrocytes
erythrocytes in homogeneous columns and other cellular blood elements, genera-
(Fig. 4–41). ting the increase of plasma viscosity and
decrease of fluidity and perfusion of blood
in the vascular system. It is conditioned
by the changes of physical and chemical
properties of erythrocytes. There is no he-
molysis and coagulation of blood in stasis.
It is a nonspecific process, which occurs
in cases of severe circulation disturbances
(cardiac valvulopathies, myocardial infarc-
tion), infectious diseases (malaria, typhus),
intoxications, under the action of some
physical factors (high temperature, cold).

It is a reversible process, but a prolonged
Fig. 4–41. Stasis in myocardium capillaries (he- stasis causes hypoxia of the respective ter-
matoxylin–eosin stain; ×110). ritory and dystrophic and necrotic lesions.
4. 9. SHOCK
The shock is a complex pathological According to etiology and pathoge-

condition, characterized by acute reducti- netic mechanisms, the following main
on of the blood flow (circulatory collap- varieties of shock are distinguished:
se), generalized hypoperfusion of tissues ²² hypovolemic – caused by the de-
and insufficient oxygen and nutritive crease of the volume of the circu-
substances supply to the cells/tissues. lating blood, dehydration of the
As a result of the critical decrease of organism or the peripheral vasodi-
blood circulation intensity at the level of latation; it appears in blood losses
micro-vessels, especially of capillaries, a (gastro–intestinal hemorrhages,
severe energetic deficit and accumulation traumas, rupture of aortic ane-
of intermediate products of metabolism urysm) or plasma losses (by vomi-
occurs, with destructive lesions in tissues/ ting, diarrhea, burns);
organs and polyorganic insufficiency. ²² traumatic – conditioned by many

pathogenetic factors, like pain, to- certain allergic substances, inclu-
xemia, hemorrhage; it develops in ding medicines.
the syndrome of prolonged crush Morphological manifestations of the
of the soft tissues (crush–syndro- shock:
me), burns; ²² redistribution of blood with its
²² cardiogenic – a result of such fac- accumulation in the microcircula-
tors like contractile insufficiency tory bed;
of heart, fatal arrhythmias, pain; it ²² the syndrome of disseminated in-
may occur in the acute period of travascular coagulation;
the myocardial infarction, throm- ²² in kidneys – dystrophic lesions and
boembolism of pulmonary arteries, necrosis of convoluted and straight
myocardial contusion, pericardial tube epithelium (shock kidneys), in
tamponade, acute myocarditis; some cases – symmetrical cortical
²² septic (toxico-infectious, endo- necrosis of kidneys;
toxic) – conditioned by bacterial ²² in adrenals – hemorrhages and ne-
endo- and exotoxins; it may be ob- crosis of the cortical layer (Water-
served in peritonitis, pneumonia, house–Friderichsen syndrome);
urinary and biliary tract infection, ²² in lungs – adult respiratory distress
pancreatonecrosis, puerperal sepsis, syndrome (shock lung);
septic abortion; ²² in liver – stasis, hydropic dystrophy
²² neurogenic – the starting moment of hepatocytes and centrolobular
is constituted by excessive afferent necrosis;
impulse, especially the painful one, ²² in gastrointestinal tract – erosions
or interruption of the sympathetic of mucosa and acute multiple ul-
innervations; it appears in trauma- cers (stress ulcers);
tisms of the spinal cord and com- ²² in brain – ischemia, with foci of he-
plications of spinal anesthesia; morrhages and edema;

²² anaphylactic – it appears as a re- ²² in myocardium – dystrophic chan-
sult of immediate immune reacti- ges and small foci of necrosis of
on, when reagin-type antibodies cardiomyocytes.
– IgE fix on mast cells and baso- Morphological lesions, which appear
philes of the blood, causing hista- in shock states, determine functional dis-
mine release; it can be seen in cases turbances of the respective organs and
when the organism is sensitive to the polyorganic insufficiency syndrome.
4 . 1 0 . D I S S E M I N AT E D I N T R AVA S C U L A R
C OA G U L AT I O N ( D I C S Y N D RO M E )
DIC is characterized by formation of sions and microinfarcts in all the organs,
multiple thrombi in small blood vessels but more frequently in lungs, kidneys,
(arterioles, capillaries, venules), which ge- brain, digestive tract, adrenals and skin.
nerates the consumption of coagulation These microinfarcts are associated with
factors, fibrinogen (hypofibrinogenemia) the noncoagulability of the blood and
and other procoagulant proteins (con- the hemorrhagic syndrome with multiple
sumptive coagulopathy), reduction of the hemorrhages in parenchymatous organs
number of platelets (thrombocytopenia). and teguments. It occurs in various shock
Microthrombi cause severe dystrophic le- conditions, severe infections (sepsis, me-

ningococcemia), intoxications, leukemias, consists in the impairment of the balan-

traumatisms with massive tissue injuries, ce between the coagulation and antico-
burns, obstetrical complications with agulation systems. Consequently, acute
amniotic fluid, eclampsia and uterine he- polyorganic insufficiency develops.
morrhages. The pathogenetic mechanism
4. 11. EDEMA
Edema is the increase of fluid in tis- date is transparent and contains up to
sues and serous cavities. The edema fluid 1–2 % of serum proteins, being slightly
is accumulated in the extracellular com- associated with the proteins and glyco-
partment (interstitium). saminoglycans of the ground substance
The edematous fluid or the transu- of the interstitial tissue.
4. 11. 1. PATHOGENETIC MECHANISMS IN DEVELOPMENT OF EDEMAS
I. Vascular factors: colorless or a slight eosinophilic (rosy)

a. increase of hydrostatic pressure of homogeneous aspect; the fluid is accu-
the blood in small vessels; mulated especially in the perivascular
b. decrease of oncotic pressure of area; the lymphatic vessels are dilated
blood plasma; (Fig. 4–42 and 4–43).
c. increase of permeability of ca-
pillary and venule walls;
d. lymphatic stasis.
II. Tissular factors:
a. retention of electrolytes in tissues,
especially of sodium and water;
b. increase of oncotic pressure of in-
1 0 0  G E N E R A L M O R P H O P A T O L O G Y IEREMIA ZOTA, VLADIMIR VATAMAN
terstitial fluids.
Macroscopically, the edematous
tissues (organs) are increased in volu-
me, tumefied; the lax tissue consistency
is paste-like, gelatinous, a depression Fig. 4–42. Pulmonary edema (hematoxylin–eo-
remains at digital pressure; the bony sin stain; ×70).
contours are erased in the region of ex-
tremities; the parenchymatous organs
are increased, the capsule is distended,
the consistency is increased, wet, shiny
aspect on section, low temperature, the
color is paler than normally (as a result
of capillary compression), a colorless or
pale–yellowish fluid leaks from the sur-
face when sectioned.
Microscopically, one notices a
dissociation of the fibrillar and cellular
structures by the edema fluid, which, Fig. 4–43. Cerebral edema (hematoxylin–eosin
stained with hematoxylin–eosin, has a stain; ×110).

4. 11. 2. CLASSIFICATION OF EDEMAS ACCORDING
TO ITS PATHOGENETIC MECHANISMS
An edema may be generalized or lo- appearance, the edema lodges parti-
calized, chronic or acute. cularly in lower extremities and ab-
I. Generalized edemas: dominal cavity (ascites). It is noticed
Cardiac edema – the increase of hy- in cases of malnutrition, deficiency of
drostatic pressure in veins, as a result proteins in the diet, malabsorption di-
of heart contractile insufficiency (de- seases (chronic enterocolitis), hypovi-
compensation of the heart); retention taminoses and cachexy conditions.
of sodium, as a result of increase of II. Localized edemas:
aldosterone secretion. The predomi- Stasis edema – the increase of pressure
nant edema localization is in the lower in veins or lymphatic vessels. The ede-
extremities (due to the gravity force); ma is lodged in the area of the occlu-
the teguments have a cyanotic aspect ded vessel and has a cyanotic aspect.
(cyanotic edema). It is seen in cardiac It can be seen in thrombophlebites, in
valvulopathies, infective endocarditis, cases of compression of a vein or of a
diffuse myocarditis, pericarditis, diffu- lymphatic vessel (by tumors, adheren-
se cardiosclerosis, severe chronic cardi- ces, ligatures).
ac arrhythmias, cardiomyopathies etc. Inflammatory edema – hemodynamic
Renal edema - is the decrease of onco- disturbances in the microcirculatory
tic pressure, as a consequence of pro- system and increase of permeability
teinuria, sodium retention. Initially, it of capillaries, due to the action of in-
appears in the lax connective tissue of flammatory mediators (histamine,
the face (eyelids), further - on the dor- serotonin). The edema lodges around
sal surfaces of hands and legs, in the the inflammatory focus. It can be seen
scrotum area; gradually, the edema be- in different inflammatory processes,
comes generalized; the teguments get especially in exsudatives.
a pale aspect (white edema). It occurs Angioneurotic edema (anaphylactic) –

in nephrites, nephrotic syndrome and the increase of vascular permeability,
acute renal insufficiency. as a result of the action of histamine
Dystrophic edema (deficient, cachetic, and other substances of histaminic
starvational, nutritional) – the decre- type, released by labrocytes during
ase of oncotic pressure due to prote- allergic reactions (hypersensitivity) of
in insufficiency in the blood (hypo- immediate type. The edema has a whi-
proteinemia); the increase of vascular te aspect and appears suddenly, more
permeability, as a result of intratissu- frequently in the facial area (eyelids,
lar tension decrease (disappearance lips); larynx, glottis, trachea, bronchi,
of adipose tissue, muscular atrophy). genital organs. It is seen in Quincke
The edematous tissues have a whitish edema, nettle rash.
4. 11. 3. TERMINOLOGY OF EDEMAS
a. Hydropsy (Latin hydrops) – genera- used to name the accumulation of

lized edema, accumulation of edema fluid in serous cavities.
fluid (transudate) in tissues and ca- b. Anasarca (Latin anasarca) – accu-
vities of the body, especially in sub- mulation of edema fluid in the sub-
cutaneous tissue, serous cavities and cutaneous adipose tissue (generalized
parenchymatous organs. It is mostly edema of subcutaneous tissue).

c. Ascites or hydroperitoneum (Latin mulation of fluid in the vaginal tuni-

ascites s. hydroperitoneum) – accumu- ca of the testicle (testicular hydropsy).
lation of edema fluid in abdominal g. Hydrocephaly (Latin hydrocephalia)
(peritoneal) cavity. – excessive accumulation of cerebro-
d. Hydrothorax (Latin hydrothorax) – spinal fluid within the cranial cavity.
edema in the pleural cavity (uni– or It may be internal (in the cerebral
bilateral). ventricle cavities) and external (in the
e. Hydropericardium (Latin hydro- subarachnoid space).
pericardium) – pericardial hydropsy, h. Hydrarthrosis (Latin hydrarthrosis)
accumulation of edema fluid in the – accumulation of edema fluid in the
pericardial sac. cavity of a joint.
f. Hydrocele (Latin hydrocele) – accu-
4. 12. LYMPHATIC CIRCULATION DISTURBANCES
According to the character of distur- tent dilatation of lymphatic vessels).

bances, there are three types of lympha- Consequently, there may deve-
tic circulation insufficiency: mechanical, lop a lymphedema (lymphatic edema),
dynamic and resorptional. lymphorrhage or lymphoreea (the
I. Mechanical insufficiency of the leakage of lymph from lymphatic vessels),
lymphatic circulation is caused by the in- lymphatic or lymphovenous fistulae,
crease of the general venous pressure, lo- lymphogenic sclerosis of tissues. The
cal or regional, compression of lymphatic lymphatic stasis has a sclerogenic action
vessels (tumors, scars, adherences, ligatu- because it causes tissular hypoxia and ex-
res), their occlusion (parasites, thrombi, cessive proliferation of connective tissue
tumoral emboli), interruption of lympha- (activation of fibroblasts). Edematous tis-
tic ways (surgical extirpation of vessels sues are increased in volume, the contours
and lymph nodes, for example, in malig- become erased, the skin is hard, thicke-
nant tumors), insufficiency of lymphatic ned; these changes are called elephantiasis
vessel valves, etc. and occur more frequently in extremities
II. Dynamic insufficiency is deter- and genitalia. Lymphorrhage may lead to
mined by the discrepancy between the appearance of chylous ascites (accumu-
excess of fluid in tissues and its intensity lation of lymph in peritoneal cavity) or
(rapidity) of elimination. The main causa- chylothorax (accumulation of lymph in
tive factor is the excessive filtration of the pleural cavities).
fluid in capillaries, formation of a large
quantity of interstitial fluid, the lympha-
tic system being unable to eliminate it.
III. Resorptional insufficiency is
conditioned by the decrease of lymphatic
capillary permeability or by the change of
tissular protein composition, causing wa-
ter retention in tissues.
Lymphatic stasis is manifested
morphologically through dilatation of
lymphatic vessels (Fig. 4–44), appearance Fig. 4–44. Lymphatic stasis in the wall of the
of collaterals, lymphangiectases (persis- small intestine (hematoxylin–eosin stain; ×70).

ESSENTIAL TERMS
on the subject “THROMBOSIS. EMBOLISM. EDEMA. SHOCK”
air embolism gaseous embolism recanalization of thrombus

anaphylactic edema hyaline thrombus red thrombus
anaphylactic shock hydrarthrosis renal edema
anasarca hydrocele retrograde embolism
angioneurotic edema hydrocephaly septic shock
ascites hydropericardium shock
autolysis of thrombus hydroperitoneum “sick” thrombus
cardiac edema hydropsy stasis
cardiogenic shock hydrothorax stasis edema
cellular embolism hypovolemic shock thromboembolism
chylothorax inflammatory edema thrombolysis
L
chylous ascites lymphedema thrombosis
consumptive
lymphorrhage thrombus
coagulopathy
DIC-syndrome lymphorrhea tissular (cellular) embolism
direct (forward)
lines of Zahn transudate
embolism
dystrophic edema microbial embolism traumatic shock
edema mixed thrombus vascularization of thrombus
embolism neurogenic shock Virchow’s triad
fat embolism organization of thrombus white thrombus
fibrinolysis paradoxical embolism

foreign body
postmortem clot
embolism
TESTS
on the subject “THROMBOSIS. EMBOLISM. EDEMA. SHOCK”
SET I.
Multiple-choice questions with one cor- a) kidneys;

rect answer b) lungs;
1. Which of the listed factors has a determi- c) liver;
nant role in the venous thrombosis: d) brain;
a) blood stasis; e) stomach.
b) reduction of number of platelets; 3. Thromboembolism, which starts in pari-
c) fibronectin; etal thrombi from the left ventricle, can
d) cardiac output; be in the vessels of all the listed organs,
e) decrease of prothrombin level. except for:
2. Thromboembolism from the lienal vein a) brain;
can occur in the vessels of which organ: b) lungs;

c) colon; and aged persons;

d) spleen; d)the majority of pulmonary throm-
e) kidneys. boembolisms are of arterial origin;
4. Which of the statements that refer to e) all the statements are correct.
thromboembolism of the pulmonary ar- 5. All the listed pathological processes may
tery is correct: cause edemas, except for:
a) the majority of pulmonary throm- a) cardiac insufficiency;
boembolisms are fatal; b) renal insufficiency;
b) the majority of pulmonary throm- c) arterial occlusion;
boemboli originate from lower ex- d) lymphatic occlusion;
tremity veins; e) venous occlusion.
c) the majority of pulmonary throm-
boembolisms occur in children
SET II.
Multiple-choice questions with 2, 3 or b) friable;
more correct answers. c) adherence to the vascular wall;
1. Which of the below listed pathological d) elastic consistency;
processes can cause per rhexin hemorr- e) lines of Zahn.
hage: 4. In the vessels of which organs parado-
a) arterial aneurysm; xical thromboembolism can occur, if the
b) enzymatic action on the vascular starting point of the emboli are the su-
wall; perficial veins of lower extremities:
c) increase of permeability of the a) brain;
vascular wall; b) kidneys;
d) transmural myocardial infarction; c) lower extremities;

e) arterial hypotension. d) lungs;
2. Which of the listed diseases may compli- e) spleen.
cate with hemorrhage per diabrosin: 5. In the vessels of which organs direct
a) arterial hypertension; thromboembolism from the femoral vein
b) gastric erosions; can occur:
c) tubal pregnancy; a) spleen;
d) pulmonary abscess; b) lungs;
e) vitamin C deficiency. c) liver;
3. Which of the listed signs are not characte- d) brain;
ristic for thrombi: e) myocardium.
a) smooth surface;

SET III.
The classification tests include 2 – 4 sub- III – microbial embolism;
jects and a series of answers. Indicate which a) it is often seen in multiple fractu-
answers are correct for each separate sub- res of bones;
ject. b) it is seen in traumas of subcuta-
1. In the vessels of which organs listed neous adipose tissue in the obese;
below direct thromboembolism may occur, if c) it occurs in malignant tumors;
the initial localization of the thrombus will d) it occurs in septicemia;
be: e) to diagnose one uses the Sudan
I – tricuspid valve; III stain;
II – aortic valves; f ) destruction of cardiac valves in
III – pelvic veins; infective endocarditis.
IV –aortic bifurcation area; 4. In which of the listed diseases develop the:
a) pulmonary vessels; I – hypovolemic shock;
b) brain vessels; II – cardiogenic shock;
c) lienal vessels; III – traumatic shock;
d) kidney vessels; IV – endotoxic shock;
e) intestinal vessels; a) heart rupture;
f ) vessels of lower extremities. b) severe infections;
2. Which of the elements listed below are c) massive hemorrhages;
characteristic for: d) multiple bone fractures;
I – air embolism; e) extended burns;
II – gaseous embolism; f ) repeated vomiting and diarrhea;
a) it is seen in the atony of the ute- g) rupture of aortic aneurysm.
rus after delivery; 5. Which of the listed elements characte-

b) it is produced in cervical injuries; rize the:
c) it is frequently complicated with I – anasarca;
foci of ischemic necrosis in the II – elephantiasis;
brain and spinal cord; a) it can be seen in occlusion of
d) it manifests itself by dilatation of lymphatic ways with cancerous
the right heart cavities; cells;
e) it may occur in pilots in case of b) it is accompanied by hydrothorax,
rapid rising or landing; ascites, hydropericardium;
f ) to diagnose it, it is necessary to c) it is caused by chronic cardiac in-
pierce the right heart under water, sufficiency;
filling the pericardium with water e) generalized edema with marked
beforehand. tumefaction of the subcutaneous
3. Which of the elements listed below cha- tissue;
racterize the embolism: f ) it is one of the consequences of
I – fat embolism; extirpation of regional lymph no-
II – cellular (tissular) embolism; des in different forms of cancer.

Daily practice cases are presented suspected of thromboembolism of cere-

with clinical and morphological data bral arteries.
from clinical histories and/or from necro-
psy protocols. Each subject includes simple Questions:
or multiple - answer questions, with 1, 2 A) According to the direction of embo-
or more correct answers. lus circulation, which variant of embolism
1. A patient, who suffered a sub- occurred in the given case:
endocardial myocardial infarction, lost a) indirect;
suddenly the sight in her right eye. The b) retrograde;
ophthalmologist detected dilatation of c) direct;
the central artery of retina and a blood d) collateral;
clot in its lumen. The echocardiography e) paradoxical.
revealed a parietal thrombosis in the left B) Which organ should be examined in de-
ventricle. tails in order to confirm the diagnosis:
a) lower extremities;
Questions: b) lungs;
A) Which is the cause of development of in- c) heart;
tracardiac thrombosis in case of suben- d) spleen;
docardial myocardial infarction: e) liver.
a) blood stasis; C) Which variant of cerebral infarction has
b) reactive inflammation of endo- developed in this case:
cardium; a) hemorrhagic;
c) blood flow turbulence; b) ischemic;
d) thrombocytosis; c) ischemic with hemorrhagic bor-
e) myomalacia. der;
B) What pathological process caused the d) mixed;
loss of sight: e) hematoma.
a) thrombosis; 3. An 18-year-old girl fell down from
b) artery spasm; a swing and suffered multiple fractures
c) thromboembolism; of the leg bones from both sides. She
d) embolism with cholesterol crys- was taken to traumatology department
tals; without immobilization of the fractured
e) cellular embolism. extremities. She died in 24 hours becau-
2. A 38-year-old patient underwent se of acute respiratory insufficiency.
hemorrhoidectomy. In 6 hours after the
surgery, there appeared signs of acute Questions:
disturbances of cerebral circulation, pa- A) What complication can be suspected
ralysis of half of the body and, in 24 ho- in this case:
urs, the patient died because of cerebral a) fat embolism;
edema with dislocation of brainstem (its b) air embolism;
enclave in the big occipital hole). One c) thromboembolism;

d) microbial embolism; of the development of this syndrome:
e) gaseous embolism. a) thrombocytosis;
B) Which organ must be examined in b) erythrocytosis;
details to confirm the diagnosis: c) hyperfibrinogenemia;
a) heart; d) consumptive coagulopathy;
b) liver; e) thromboembolic syndrome.
c) lungs; 5. A 17-year-old girl presents ge-
d) kidneys; neralized edemas, more emphasized in
e) brain. lower extremities, which appeared after
C) What histochemical reactions should 3 weeks of artificial hunger in order to
be applied to confirm the diagnosis: lose weight.
a) hematoxylin and eosin;
b) Congo red; Questions:
c) carmine; A) Which variant of edema has develo-
d) Sudan III; ped in this case:
e) Sudan IV. a) allergic;
4. At the necropsy of a young man b) angioneurotic;
who died of polyorganic insufficien- c) hypoproteinemic;
cy due to a venous snake bite, multi- d) renal;
ple thrombi were revealed in the mi- e) cardiac.
cro-vessels of the lungs, brain, kidneys, B) Which are the criteria of differenti-
gastrointestinal tract, liver, adrenals and ation of transudate from exudate:
skin. Concomitantly, multiple petechiae a) transparent;
hemorrhages were observed in the lungs, b) dim;
brain, as well as dystrophic lesions in tis- c) rich in proteins;
sues and organs. d) poor in proteins;

e) rich in cellular elements;
Questions: f ) poor in cellular elements.
A) Which variant of hemodynamic di- C) The name of generalized edemas
sorders has developed in this case: with accumulation of fluid in the subcuta-
a) generalized venous hyperemia; neous adipose tissue:
b) systemic thrombosis; a) hydropsy;
c) hemorrhagic syndrome; b) hydrothorax;
d) DIC syndrome; c) hydroperitoneum;
e) marantic thrombosis. d) anasarca;
B) What is the pathogenetic mechanism e) ascites.

Chapter 5 INFLAMMATION
INFLAMMATION
Inflammation (Latin inflammare – delimitation (for example, in foreign

kindling) – local organism reaction to body granulomas) and reestablishment
tissue alteration, due to different patho- of structure and function of the inju-
genic factors. It is a defensive reaction red tissue. The inflammatory process is
directed towards elimination (for exam- firstly manifested by modification of the
ple, bacteria elimination through exuda- microcirculatory system, connective tis-
tes), inactivation (for example, bacte- sue and blood vessels. The inflammation
ria phagocytosis) or pathogenic agent occurs only in vascularized tissues.
5.1.CAUSES, MORPHOLOGY, TERMINOLOGY

AND CLASSIFICATION OF INFLAMMATION
The inflammation can be caused by coagulation factors, complement, ara-
different physical, chemical and biologi- chidonic acid derivatives and cytokines.
cal factors of exogenous and endogenous According to the origin, inflammation
origin, which have a harmful action on mediators can be cellular (tissular) and
tissues, causing cellular/tissular injuries. plasmatic. The most important source
Morphologically, one distinguishes 3 of active amines is mastocytes, which

stages in the evolution of the inflamma- produce histamine, serotonin and he-
tory process: 1) alterative; 2) exudative; parin. Basophilic leukocytes, platelets,
3) proliferative. lymphocytes, monocytes, macrophages,
Dystrophic and necrotic modificati-
ons are produced in the lesion focus, in
the first alterative stage of inflamma-
tion. Both parenchymatous cells and
ground substance, cellular and fibrillar
elements of connective tissue (Fig. 5–1)
are affected.
Consequently, some biologically ac-
tive substances – the so–called chemical
mediators of the inflammation are ela-
borated. These substances act on blood
vessels, determine the evolution of the Fig. 5–1. Diphtheric myocarditis: vacuolar
inflammatory process and the appearan- dystrophy and coagulation necrosis of cardi-
ce of exudative reaction. The most im- omyocytes, mononuclear cell infiltration (he-
portant mediators are biogenic amines, matoxylin–eosin stain; ×70).

INFLAMMATION Chapte r 5
endotheliocytes also produce a wide important role among plasmatic media-
range of pro-inflammatory mediators tors is played by the kinins (bradykinin,
(leukotrienes, prostaglandins, thrombo- kallikrein,) some components of the
xanes, cytokines etc.). These substances complement and coagulation and anti-
can be eliminated from the cells via 2 coagulation system of the blood.
ways: a) through exocytosis – a process The II exudative stage of the in-
which reminds secretion (it is observed flammation is determined by chemical
in leukocytes) and b) through degra- mediators (primarily histamine and se-
nulation – expulsion of granules from rotonin) and is manifested through 3
cytoplasm and their further disinte- important processes:
gration in the extracellular space (it is a. dilatation of the microcirculatory
observed in mastocytes) (Fig. 5–2). An system vessels and blood flow dis-

a b
Fig. 5–2 a, b. Degranulation of mastocyte: a - microscopic pattern (azure–eosin stain; ×70); b –

electron microscopic picture (×1000); G – granules of mastocytes, N – nucleus.
turbance (modification of blood modifications are manifested through
rheological properties); redness and local fever (heat).
b. exudation (extravasation) of plasma; Extravasation from vascular bed is
c. migration of blood cells. determined by the raise of the hydrosta-
Dilatation of the microcirculatory tic pressure and permeability of the mi-
bed vessels. Initially, a short-term va- crocirculatory system vessels, mainly of
soconstriction of arterioles appears in the venules. The increase of permeabi-
the inflammatory focus (some seconds lity, at the initial stage of the inflamma-
or minutes). Later, a dilatation of arte- tion, is due to formations of some fis-
rioles, capillaries and venules (mainly sures among endothelial cells, which
of postcapillaries and venules) develops appear through contraction of endothe-
fast under the action of histamine; this liocytes, under the action of bradykinin
determines an increased blood flow and and histamine. Intensification of the pi-
active inflammatory hyperemia of the nocytosis processes takes place later in the
lesion focus. Clinically, these vascular endotheliocytes of the vascular walls and

plasma is evacuated through basement cytes margination, when they detach

membrane, which also has an increased from the axial area of the blood column,
permeability (Fig. 5–3). These modi- constituted from cellular elements, mov-
ing towards the vascular wall (Fig. 5–4).
Neutrophils extend on the endothelial
surface and gradually form a continuous
Pv leukocyte layer. Activation of leukocytes
and endotheliocytes leads to expression
of adhesion molecules – integrins - and
establishment of close contacts between
Er
N
En
BM
Fig. 5–4. Venule dilatation, hyperemia and
leukocytes margination (hematoxylin–eosin
stain; ×110).
these cells. Further on, leukocytes is-
sue cytoplasmatic expansions (pseudo-
Fig. 5–3. Pinocytosis in the endothelium of ca- pods), which slip actively at the junction
pillary in inflammation (electron microscopy level, among endotheliocytes (interen-

×1000): Pv – pinocytic vesicles, En – endothe-
dothelial), in the subendothelial space
liocyte, Er – erythrocyte, BM – basement mem-
brane, N – nucleus.
(Fig. 5–5). Leukocytes change their form
during migration due to polymerization
fications are stimulated by the VEGF and redistribution of microtubules and
(vascular endothelial growth factor). Con- microfilaments of the cellular cytoskel-
sequently, the active transendothelial eton. After this, neutrophils penetrate
transport of blood plasma, fluid accu- the basement membrane within the
mulation in tissues (in the extravascular thixotropy phenomenon (modification
spaces) and appearance of inflammatory of colloidal state of the ground sub-
edema and local tumefaction are produced. stance of the basement membrane) and
Inflammatory edema is partly caused by penetrate in the perivascular connective
the decrease of plasma oncotic pressure, tissue (Fig. 5–6). The fact that leuko-
as a consequence of loss of proteins with cytes secrete collagenases is also impor-
the extravasated plasma fluid. tant, as they increase the permeability of
Migration of the blood cells rep- the basement membrane. The leukocyte
resents the main aspect of the cellular diapedesis takes place predominantly in
stage of the inflammatory reaction. This postcapillaries and venules, and in the
process begins with neutrophil leuko- lungs – at the level of septal capillaries as

NL well. Active migration of monocytes and
eosinophils occurs according to the same
N mechanism, and lymphocytes cross the
vascular wall through endothelial cell
NL BM N cytoplasm (transendothelial). Erythro-
CL J cytes strain the vascular wall passively,
NL
En through the same holes as neutrophils
CF (Fig. 5–7). Basement membrane integ-
J rity is reestablished after cell migration.
NL Polymorphonuclear neutrophils that
reached the perivascular space move ac-
NL tively towards the pathogenic agent by
5-5 ameboid movements, by means of cyto-
I En NL II N
endotheliocyte
leucocyte
erythrocyte
leucocyte
monocyte
En leucocyte

Fig. 5–7. Blood cell migration scheme in in-
flammation
plasm expansions, whose length can be
10 times longer than leukocyte’s diam-
eter. The travel speed of the neutrophil
J is nearly 0,02 mm per minute. This ori-
ented (directed) movement of neutro-
phils is due to substances with a positive
chemotactic action – the so–called at-
CL tractant substances (immune complexes,
5-6 complement activation products, bacte-
rial exotoxins, arachidonic acid deriva-
tives, mitochondrial polypeptides from
Fig. 5–5, and 5–6. Migration of neutrophil
leukocytes in inflammation (electron micro- the injured cells).
scopy; Fig. 5–5/I and 5-6 ×12000, Fig. 5–5/II The main function of polymorpho-
×20000): NL – neutrophil leukocyte, En – en- nuclear leukocytes and monocytes in the
dothelium, BM –basement membrane, N – nu- inflammation area is phagocytosis – en-
cleus, J – junction between endotheliocytes, CF gulfing of some microorganisms, tissu-
– collagen fibers, CL – capillary lumen. lar remnants, foreign micro-particles or

other substances and their intracellular dergo dystrophic modifications, espe-

destruction (digestion). Neutrophils cially fat dystrophy and die, but mono-
are specialized cells which possess the cytes survive for a long time due to their
capacity to phagocyte small bodies, es- capacity of new lysosomes production
pecially microorganisms (microphages); and resynthesis of lysosomal enzymes.
monocytes and histiocytes phagocyte Phagocytosis may be complete and in-
big particles, for example foreign bodies complete. The latter may favor dissemi-
(macrophages). The phagocytosis process nation and generalization of infection.
includes 2 main stages: 1) attachment of Phagocytosis is the key phenomenon of
particles or microbes to the phagocyte the inflammatory process.
membrane, its invagination and their As a consequence of these processes,
penetration into the cytoplasm; 2) for- firstly of plasmatic fluid extravasation
mation of phagocytic vacuoles (digestive and migration of blood cells, exudates
vacuoles) around the engulfed particles (inflammatory fluid) are formed in tis-
and their intracellular digestion by the sues as an inflammation final product
action of lysosomal enzymes (Fig. 5–8). (Fig. 5–9 and 5–10).
Bacteria attachment to the leukocy- The main components of the exuda-
te membrane is facilitated by opsonins te are:
(Greek opsonion = spice) – proteic mole- a) fluid part – water with proteins
cules which are normally found in blood (albumins, globulins, fibrinogen),
nuc
gr
st
st
gr
nuc
Fig. 5–8. Phagocytosis (electronic microscopy; Fig. 5–9. Serous focal pneumonia (hemato-
×1500): st – staphylococci, vac – digestive vacu- xylin–eosin stain; ×110).
ole, gr – lysosomal granulations, which contain
hydrolytic enzymes, nuc – nucleus.
plasma and in the interstitial fluid. The

main opsonins are immunoglobulins G,
the complement component C3, some
pectins. The bactericidal action is made
by means of different mechanisms:
lysosomal enzymes, cationic proteins,
hypochlorous acid and other bioactive
substances. Neutrophil leukocytes un-
Fig. 5–10. Purulent pleuritis.

their content being higher than
3%;
b) cellular elements of hematogenic
(especially leukocytes and mono-
nuclear phagocytes) and histioge-
nic origin (local connective tissue
cells and epithelial, parenchyma-
tous cells);
c) products of tissue destruction (tis-
sue detritus).
The consistency, aspect, color, cha-
racter of the exudate depend on the pro- Fig. 5–11. Clinical signs of inflammation (heat,
portion of its components. redness, swelling, pain, loss of function) (by D.
Exudate accumulation in the in- A. Wiloughby and W. G. Spector, 1968).
flammatory focus produces local tissue
tumefaction and pain. The pain is ge-
nerated by nerve endings compression
due to tissular tension, caused by the
inflammatory edema and their excitati-
on by chemical mediators (bradykinin,
prostaglandins). Pain and local tumefac-
tion determines function disturbance of
the inflamed organ (tissue).
Accordingly, the local clinical sings
of inflammation are the following (Fig.
5–11, 5–12, 5–13):

1) redness (rubor);
2) local fever (calor);
3) tumefaction (tumor);
4) local pain (dolor); Fig. 5–12. Furuncle (purulent inflammation of
5) loss of function (functio laesa). the pilosebaceous follicle).
General (systemic) manifestations
of inflammation are fever, tachycardia,
tachypnea, leukocytosis, ESR increase
(erythrocyte sedimentation rate), general
intoxication, which is manifested throu-
gh poor appetite, tiredness, sleepiness etc.
The III proliferative stage of the
inflammatory process manifests itself
through cellular element multiplication
in the inflammatory focus. Vessel hype-
remia, plasma extravasation and cell mi-
gration in tissues diminish gradually, the Fig. 5–13. Inflammatory hyperemia and edema
affected area being delimited from the of skin (purulent inflammation of the piloseba-
adjacent tissues. ceous follicle); (hematoxylin–eosin stain; ×70).

The localized agglomeration of cells a) causative factor features (for

in the inflammatory focus is called in- example, in lungs, pneumococcus
flammatory infiltrate. It is composed of causes more frequently fibrino-
lymphocytes, plasmocytes, macrophages us inflammation, staphylococcus
and their derivatives; leukocytes are ra- aureus – purulent inflammation,
rely met (Fig. 5–14) influenza virus – hemorrhagic in-
The cells from the infiltrate perform flammation);
certain functions, for example, macro- b) inflammatory process localization
(the structural and functional parti-
cularities of the organ, for example,
the lungs have a lax structure, the
bones – a hard, compact structure);
c) reactivity state of the macroor-
ganism (for example, in immune
deficiency cases, the inflammatory
reaction is more severe and exten-
ded, having the tendency for mor-
bid process generalization).
Inflammation terminology: the
suffix –itis is added to the Greek or La-
Fig. 5–14. Cellular inflammatory infiltrate in fo- tin organ name root. For example, myo-
cus of inflammation (lymphocytes, plasmocytes, card–itis, gastr–itis, nephr–itis, hepat
macrophages); (hematoxylin–eosin stain; ×70). – itis, mening – itis etc. Latin or Greek
phages – phagocytosis, lymphocytes and terms are used in the medical literature
plasmocytes – immune processes etc. A concerning the inflammation of one or
part of the cells die in time and others other organ. For example, fallopian tube
transform gradually in fibroblasts. Fi- inflammation – salpingitis (tube = Gr. –
salpinx, Latin – tubus), kidney inflamma-

broblasts synthesize collagen and glyco-
tion – nephritis (kidney = Gr. – nephros,
saminoglycans, which assemble extra-
Latin – ren) etc. The inflammation of
cellularly in collagen fibrils and the
some organs/tissues has specific names,
inflammatory process ends with fibrillar
for example furuncle – pilosebaceous
connective tissue formation. follicle inflammation, empyema – in-
Consequences of inflammation – flammation of some cavities with accu-
regeneration and recovery of altered tis- mulation of purulent exudate in them,
sues. In cases of small inflammatory foci, pneumonia – pulmonary parenchyma
a complete recovery with exudate resor- inflammation with exudate formation in
ption and tissue detritus by means of the alveoli, pneumonitis – inflammation
phagocytes and their elimination takes of the interstitial tissue of the lungs etc.
place. In case of extensive and profound Inflammation classification
defects, the regeneration is incomplete, Morphologically, inflammation is
partial, the inflammatory focus being subdivided in:
substituted with cicatricial fibrocon- 1) exudative;
nective tissue (fibrosis and sclerosis). 2) proliferative (productive).
The inflammation character de- A severe alterative reaction takes
pends on: place in some cases of severe toxic in-

fections, allergic diseases, with tissues inflammation can be distinguished:
necrosis. Such inflammatory processes ²² acute (lasts not more than 2–3
can be defined as alterative or necrotic weeks); it is usually an exudative
inflammation, for example, alterative inflammation;
myocarditis in diphtheria, allergic ne- ²² chronic (lasts months and years);
crotic vasculitis etc. the inflammation has a prolifera-
Clinically, the following forms of tive character.
5.2. ACUTE (EXUDATIVE) INFLAMMATION
It is an immediate reaction to a tis- According to the exudate features,

sular lesion with a sudden, short time one distinguishes the following exuda-
onset. It is characterized by predomi- tive inflammation varieties: 1) serous; 2)
nance of reaction of microcirculatory fibrinous; 3) purulent; 4) putrid; 5) he-
bed vessels and formation of exudate in morrhagic; 6) catarrhal; 7) mixed.
tissues and in body cavities.
5.2.1. SEROUS INFLAMMATION

The exudate is a yellowish, opales- serum and is poor in cellular elements
cent fluid, which contains 3–8 % of pro- (Table 5.1.).
teins (albumins); it resembles the blood
Table 5.1
Main criteria of differentiation of exudate from transudate

Fluid
Transudate Exudate
characteristics
External aspect Transparent Diffuse, opaque
Consistency Liquid Viscous
Density <1,015 g/ml >1,020 g/ml
Protein
<3 g/dl >3 g/dl
concentration
Insignificant number of mesothelial Numerous
Cell content
cells, lymphocytes, leukocytes neutrophils
Coagulation Does not coagulate Coagulates
Bacteriologic
Sterile Contains microbes
examination

The serous inflammation localizati- reabsorption, with complete recovery of

on can be various, the exudates accumu- the altered tissue, takes place, as a con-
lating in serous cavities, mucosas, me- sequence of serous inflammation.
ninges, skin (Fig.5-15 a, b), in interstitial As a rule, the serous inflammation
spaces of parenchymatous organs (myo- evolutes acutely (1–2–3 weeks) or even
cardium, liver, kidneys, lungs). Exudate very acutely (2–3 days), having usually
a b
Fig. 5–15. Epidermal vesicles with serous exudate: a – macroscopic aspect; b – microscopic pattern
a light clinical evolution. In some cases, pericarditis, serous pleuritis) or through
serous inflammation can cause major disturbance of their function (for exam-
clinical manifestations through comple, in myocarditis, hepatitis, serous glo-
pression of parenchymatous organs (in merulonephritis).
5.2.2. FIBRINOUS INFLAMMATION

It is characterized by formation The exudate has an aspect of false

of an exudate rich in fibrin. It is more membrane or pseudomembrane of whi-
frequently localized in mucous and se- tish–yellowish color on the mucous (Fig.
rous membranes, but it is also met at 5–16 a, b and 5–17) and serous surfaces
the level of parenchymatous organs, for or an aspect of dense mass formed in pa-
example, in the lungs (lobar pneumonia), renchymatous organs, more frequently in
kidneys (fibrinous glomerulonephritis) lungs (Fig. 5–18). The pseudomembra-
etc. It appears in cases when the causa- ne notion is used for differentiation of
tive agent provokes a marked increase true anatomic membranes. The pseudo-
of the vascular permeability, which fa- membranous inflammation is observed
vors fibrinogen extravasation. After the in the respiratory tract (pharynx, larynx,
exit from vessels, fibrinogen coagulates trachea, bronchi), in the stomach, small
in fibrin under the action of thrombo- intestine, colon, endometrium. Lesions
plastin, which is eliminated as a result of mucosae constitute initially necrosis
of tissue necrosis. It is met in infectious of superficial layers under the action of
diseases (typical examples - diphtheria, bacterial toxins. Furthermore, necrotized
dysentery, lobar pneumonia), intoxica- epithelial cells desquamate and combine
tions (for example, in uremia) or under with the fibrinous, mucous exudate, the
the action of some physical factors (for content from lumen or respective cavity,
example, in burns). forming a coating (pseudomembrane),

Fig. 5–16 a. Croupous tracheitis in diphtheria Fig. 5–17. Fibrinous enteritis.

(diphtheric croup): microscopic pattern (hema-
Fig. 5–16 b. Croupous tracheitis in diphtheria Fig. 5–18. Lobar pneumonia (gray hepatization
(diphtheric croup): macroscopic aspect. stage).

which covers the defect and adjacent tis is covered with a whitish–yellowish
mucosa. Examined endoscopically, the mass of fibrin, which has villous aspect
respective coatings can be detached and due to the heart movements (Fig. 5–19
the subjacent mucosa with the bleeding a, b). The heart gets a hairy or “cat’s ton-
surface appears. The proteolytic activity gue” aspect (villous or hairy heart). It is
of leukocyte enzymes at the limit level met in rheumatism, tuberculosis, trans-
between live and necrotized tissue favors mural myocardial infarction, uremia etc.
the detachment of pseudomembranes. The fibrinous inflammation on the ple-
The epicardium in fibrinous pericardi- ura has a similar aspect (Fig. 5–20 a, b).
a b
Fig. 5-19 a, b. Fibrinous pericarditis (villous heart): a – macroscopic aspect; b – microscopic pat-
tern (hematoxylin–eosin stain; ×70).
a b
Fig. 5-20 a, b. Fibrinous pleuritis: a – macroscopic aspect; b – microscopic pattern (hematoxylin–

eosin stain; ×70).
There are two forms of fibrinous in- making the detachment more difficult.
flammation: croupous and diphtheroid. The necrosis in these cases is more pro-
The fibrin membrane is thin, fine in found; fibrin and necrotic mass form a
the croupous inflammation, it adheres compact common membrane, which le-
poorly to the subjacent tissues and deta- aves profound, sometimes bleeding ulce-
ches easily, due to the fact that the necro- rations after detaching.
sis of mucosae and serosas is superficial. The croupous or diphtheroid cha-
The fibrin membrane is thicker racter of the fibrinous inflammation de-
in the diphtheroid inflammation, it pends not only on the depth of necro-
adheres closely to the subjacent tissue, sis, but also on the type of the covering

epithelium of mucosae. Diphtheroid in- ces (also called symphyses or synechiae)
flammation (buccal cavity, tonsils, plica between the serous sheets, with partial
vocalis, esophagus, uterine cervix) is ob- or total cavity obliteration (pericardial,
served on membranes covered with stra- pleural, peritoneal) and functional dis-
tified squamous epithelium. Croupous turbances of the respective organs.
inflammation (upper respiratory tract, The fibrinous pericarditis results of-
gastrointestinal tract, endometrium, ten in exudate organization and forma-
pleura, peritoneum and pericardium) is tion of some adherences between peri-
observed more on mucosae covered by cardium sheets, later - in pericardial sac
glandular, monostratified epithelium obliteration. In time, calcium salts are
and on serosas (mesothelium). deposited in sclerotic serous membra-
The consequences of the fibrinous nes, which petrify or ossify (“heart in cu-
inflammation can be various: in some irass”) and this leads to chronic progres-
cases, complete resorption of exudate ta- sive cardiac insufficiency. The formation
kes place, due to the fibrinolytic action of adherences in the pleura reduces the
of leukocyte enzymes. In other cases, the amplitude of the lung respiratory mo-
fibrin is not reabsorbed, its organization vements, and peritoneal adherences can
being produced by appearance of some cause intestinal occlusion.
scars on the mucosae or some adheren-
5.2.3. PURULENT INFLAMMATION

It is characterized by predominance There are two morphological vari-
of neutrophil leukocytes in exudates, ne- ants: abscess and phlegmon.
crosis and lysis of tissues (histolysis). The abscess is a focal purulent in-
The pus is a viscous, turbid liquid of flammation, circumscribed with tissue
yellowish–greenish color, composed of lysis and formation of a cavity filled with
polymorphonuclear neutrophils, whi- pus.

ch undergo dystrophic modifications The abscess can be acute and chronic.
(mainly fat dystrophy) and disintegrate The acute abscesses are delimited from
gradually (the so–called pus globules or the respective organ’s tissue by a fibri-
pyocytes), tissular detritus and microbes. noleukocytic exudate or by granulation
The purulent inflammation is more tissue (Fig. 5–21 a), chronic abscesses
frequently caused by pyogenic bacteria
(staphylococcus, streptococcus, menin-
gococcus, bacillus coli etc.). Necrosis is
generated both by direct injury action of
pyogenic bacterial toxins on the tissues,
and by circulatory disorders (related to
vessel thrombosis or its compression by
inflammatory edema). Histolysis (pro-
teolysis) is produced through proteolytic
enzymes eliminated by live neutrophil
leukocytes or leukocytes in disintegrati-
on. A semi-liquid, viscous mass appears
Fig. 5-21 a. Cerebral abscess – microscopic pat-
after the lysis of the altered and necro- tern (hematoxylin–eosin stain; ×70).
tized tissue.

are delimited by the pyogenic membra- Consequences of abscesses may be

ne formed of granulation tissue, rich in the following ones:
capillaries, which produce intense leuko- a) organization (cicatrization);
cyte migration. Outwardly, the membra- b) petrification (condensation and
ne is formed of fibrous connective tissue pus calcification);
(Fig. 5–21 b, 5–22, 5–23 a, b). c) fistulization – fistula formation,
Fig. 5-21 b. Cerebral abscess – macroscopic as- Fig. 5-23 a. Hepatic abscesses – microscopic
pect. image (hematoxylin–eosin stain; ×70).
Fig. 5-22. Pulmonary abscesses. Fig. 5-23 b. Hepatic abscesses – macroscopic

aspect.

through which the pus is evacuated exudate spreads diffusely among tissular
externally or in a preexistent cavity elements. The pus spreads along inter-
of the body. The pathologic chan- muscular areas, adipose tissue, neurovas-
nel through which the pus drains cular trunks etc. It is caused mostly by the
is called fistula. The fragments of hemolytic streptococcus, which produces
tissue, which cannot be subject to large quantities of hyaluronidase and fi-
autolysis or organization, or cannot brinolysin. The latter alter the ground
get out because of their huge volu- substance and favor the spreading of in-
me, are called sequesters (for exam- flammatory process. It is met in adipose
ple: osseous sequesters in chronic tissues, muscles, walls of hollow and tubu-
purulent osteomyelitis). lar organs (vermiform appendix, gallblad-
The phlegmon (phlegmonous in- der, stomach, intestine etc.), in leptome-
flammation) is a purulent inflammation ninges etc. (Fig. 5–24 a, b, 5–25 a, b).
without precise delimitation, where the Macroscopically, the inflamed area
a b

Fig. 5-24 a, b. Acute phlegmonous-ulcerative appendicitis: a – macroscopic aspect; b – microscopic
pattern (hematoxylin–eosin stain; ×70).
a b
Fig. 5-25 a, b. Purulent leptomeningitis: a – macroscopic aspect; b – microscopic pattern (hemato-

is tumefied, warm on palpation, imbu- wood-like (hard phlegmon) or flaccid
ed with pus. On section, it has a dim, consistency (soft phlegmon), a fact which
yellowish–grayish color, either a hard, depends on the extension and gravity of

the necrosis processes in the respective be acute or chronic. The acute phlegmon
area (the consistency is harder in cases can lead to sepsis. Secondary amyloido-
of diffuse tissular necrosis). sis can occur in chronic forms of abscess
The phlegmonous inflammation can and phlegmon.
5.2.4. PUTRID INFLAMMATION (ICHOROUS OR GANGRENOUS)

It develops as a result of superin- with unpleasant odor (fetid). It lodges
fection of the inflammation focus with in tissues that have contact with the ex-
putrefaction bacteria (colibacilli, Prote- ternal environment (buccal cavity, lungs,
us vulgaris etc.), causing tissue putrid digestive tract, urogenital organs) – gan-
disintegration processes. The exudate grenous tonsillitis, stomatitis, pneumo-
is a grayish–greenish mass, containing nia, appendicitis, cholecystitis, colitis,
necrotic, liquefied tissue debris. The endometritis.
inflamed tissue has a dirty–grey aspect
5.2.5. HEMORRHAGIC INFLAMMATION
It is characterized by presence of a
large number of erythrocytes in the exu-
date, which gets the aspect of hemorrha-
gic liquid (Fig. 5–26). Macroscopically,
the hemorrhagic inflammation foci have
a reddish color. It is met in flu, plague,
streptococcus infection, anthrax, small-
pox, especially in patients with hemor-
rhagic diathesis or cachexy. It is related
to a marked increase of vascular perme- Fig. 5-26. Influenza hemorrhagic bronchopneu-

ability. monia (hematoxylin–eosin stain; ×110).
5.2.6. CATARRHAL INFLAMMATION

It appears at the level of respiratory teritis, colitis, cholecystitis), urogenital
tract mucosae (rhinitis, bronchitis) (Fig. tract (endometritis, salpingitis, cystitis).
5–27a, b), digestive tract (gastritis, en- Initially, the catarrh has a serous character,
Fig. 5-27. Catarrhal tracheitis: a – macroscopic aspect; b – microscopic pattern (hematoxylin–eo-

sin stain; ×110).

an abundant, yellowish–opaque liquid the catarrhal inflammation can be acute
exudate draining on the mucosal surface, and chronic. The acute catarrh heals in
which thickens gradually, becoming mu- 1–2–3 weeks. The chronic catarrh can
cous (seromucous) due to excessive mucus result in mucosal atrophy or hypertrophy,
secretion, epithelial cell desquamation impaired function of the respective or-
and migration of neutrophil leukocytes, gans. The most frequent causes of catar-
gaining a purulent aspect (mucopurulent) rhal inflammation are: viral and bacterial
in time. infections, irritating gases, toxic substan-
According to its clinical evolution, ces (uremia), thermal factors etc.
5.2.7. MIXED INFLAMMATION
The association of one type of exu- morrhagic, fibrino–purulent, fibrino–
date with other takes place in a mixed hemorrhagic inflammation etc.).
inflammation (sero–fibrinous, sero–he-
ESSENTIAL TERMS
on the subject “ACUTE (EXUDATIVE) INFLAMMATION”
abscess endocytobiosis migration

acute inflammation exocytosis phagocytosis
alteration exudate phlegmon
calor exudative inflammation pinocytosis
productive (proliferative)
catarrhal inflammation fibrinous inflammation
inflammation
cellular inflammatory
functio laesa purulent inflammation
infiltrate
chemotaxis hemorrhagic inflammation pus
chronic inflammation gangrenous inflammation putrid inflammation

complete phagocytosis ichorous inflammation pyocytes
croup incomplete phagocytosis rubor
croupous inflammation inflammation serous inflammation
degranulation inflammatory mediators subacute inflammation
diphtheroid
leukocytic margination transudate
inflammation
dolor macrophage tumor
empyema microphage
TESTS
on the subject “ACUTE (EXUDATIVE) INFLAMMATION”
SET I.
Multiple-choice questions with one cor- b) pyogenic membrane;

rect answer. c) necrosis;
1. The characteristic morphological sign of fi- d) whitish coating on the mucosal
brinous inflammation is: surface;
a) serous liquid; e) sero–hemorrhagic exudate.

2. Which definition of empyema is correct: 4. Which cells react primarily in the acute in-
a) superficial fibrinous inflammati- flammatory process:
on; a) activated B lymphocytes;
b) focal purulent inflammation b) activated T lymphocytes;
with formation of a cavity in the c) mastocytes (labrocytes);
parenchymatous organs; d) plasmocytes;
c) pus accumulation in a preexis- e) T-killer cytotoxic lymphocytes.
tent anatomical cavity; 5. All the listed cellular elements prevail in a
d) catarrhal inflammation of muco- chronic inflammatory process, with the ex-
sae; ception of:
e) diffuse purulent inflammation. a) B lymphocytes;
3. Catarrhal inflammation location is in: b) T helper lymphocytes;
a) serous membranes; c) neutrophil leukocytes;
b) myocardium; d) plasmocytes;
c) brain; e) macrophages.
d) mucosae;
e) kidneys.
SET II.
Multiple-choice questions 2, 3 or more c) catarrhal;

correct answers. d) croupous;
1. Clinical signs of inflammation: e) mixed.
a) paleness; 4. Purulent inflammation variants:
b) local temperature rise; a) cyst;
c) cyanosis; b) granuloma;
d) swelling; c) papilloma;
e) redness. d) abscess;
2. Morphological manifestations of alterati- e) phlegmon.
on: 5. Exudate variants in catarrhal inflamma-
a) necrosis; tion:
b) metaplasia; a) mucous;
c) dysplasia; b) fibrinous;
d) dystrophy; c) putrid;
e) atrophy. d) purulent;
3. Fibrinous inflammation variants: e) serous.
a) fibrinoid;
b) diphtheroid;

SET III.
The classification tests include 2 – 4 sub- the inflammatory fluid;

jects and a series of answers. Indicate which d) the morphological substratum is
answers are correct for each separate sub- the inflammatory infiltrate;
ject. e) granuloma formation is
1. Which of the enumerated signs refer to: frequently observed;
I – transudate; f ) it has an acute evolution more
II – exudate; frequently;
a) it is an edema fluid; g) the complete reestablishment of
b) contains numerous blood cells; the affected tissue takes place in
c) contains more than 2% of prote- the majority of cases.
ins; 4. Which of the listed signs characterize:
d) it is a dim liquid; I – abscess;
e) contains less than 2% of prote- II – phlegmon;
ins; a) the cavity filled with pus;
f ) contains a reduced number of b) diffuse purulent inflammation;
cells. c) presence of pyogenic membrane;
2. Which of the listed morphologic lesions d) focal purulent inflammation;
associate with inflammatory process stage: e) the pus can extend unlimitedly.
I – of alteration; 5. Which of listed morphological signs refer to:
II – of exudation; I – croupous inflammation;
a) dystrophic modifications of tis- II – diphtheroid inflammation;
sues; a) the fibrin coating is hardly elimi-
b) inflammatory hyperemia; nated;
c) epithelial cell desquamation; b) the fibrin coating detaches easi-

d) fibrinoid necrosis; ly;
e) migration of leukocytes; c) the fibrinous exudate penetrates
f ) diapedesis of erythrocytes ; deeply in tissues;
g) phagocytosis. d) the fibrin coating adheres poorly
3. What criteria characterize: to the adjacent tissue;
I – exudative inflammation; e) it is seen on the mucosae mem-
II – productive inflammation; branes covered with stratified
a) it has a chronic evolution usu- squamous epithelium;
ally; f ) it is seen on mucosae covered
b) it frequently leads to sclerosis of with glandular epithelium;
the affected organs; g) profound tissular necrosis;
c) the morphological substratum is h) superficial tissular necrosis.

Daily practice cases are presented with b) catarrhal cholecystitis;

clinical and morphological data from clini- c) purulent cholecystitis;
cal histories and/or from necropsy protocols. d) fibrinous cholecystitis;
Each subject includes simple or multiple - e) gangrenous cholecystitis.
answer questions, with 1, 2 or more correct B) What is the name of the serous mem-
answers. brane inflammation of the gallbladder?
1. A patient touched the hot iron inadver- a) paracholecystitis;
tently and the forefinger became red, with b) endocholecystitis ;
edema, severe pain, and a few minutes la- c) pericholecystitis;
ter – a vesicle filled with yellow, transpa- d) pancholecystitis;
rent liquid appeared. e) mesocholecystitis.
C) What kind of inflammation developed
Question: in the serous membrane of the gallblad-
Which variant of exudative inflammati- der:
on developed in this case: a) catarrhal;
a) fibrinous; b) fibrinous;
b) purulent; c) purulent;
c) serous; d) gangrenous;
d) hemorrhagic; e) serous.
e) gangrenous. 4. At the necropsy of a 28 year-old patient
2. In an 8-year-old child, the palatine tonsils with rheumatism, rheumatic carditis, the
are increased, edematous, hyperemic, co- following changes were detected: heart in-
vered with a whitish coat, which detaches creased in size, opaque fluid in the pericar-
easily. dium, thickened epicardium, covered with
whitish deposits, which give a rough ap-

Question:
pearance to the heart surface.
What is the correct diagnosis in the given
case: Questions:
a) fibrinous tonsillitis; A) What kind of pericarditis is in this
b) purulent tonsillitis; case:
c) serous tonsillitis; a) serous;
d) hemorrhagic tonsillitis; b) catarrhal;
e) gangrenous tonsillitis. c) purulent;
3. Postoperative material: the gallbladder is d) fibrinous;
increased in size; the wall is thickened, ede- e) gangrenous.
matous, hyperemic, yellow–greenish fluid B) What consequences are more common
in the cavity, hyperemic serosa with punc- in this form of pericarditis:
tiform hemorrhages, covered with a thin, a) resorption of exudate;
whitish coat. b) organization of exudate;
c) formation of adhesions between
Questions: serous sheets;
A) What kind of inflammation is in this d) pericardium cavity obliteration;
case: e) calcification of pericardium she-
a) serous cholecystitis; ets.

5. At necropsy in lungs was revealed a focus B) Which pathogenic agents from those
of irregular shape, consisting of necrotic de- listed below can be detected in this case:
composing black mass with a fetid smell. a) flu virus;
b) diphtheria bacillus;
Questions:
c) clostridium perfringens;
A) Which type of inflammation is in the d) Staphylococcus aureus;
given case: e) coli bacillus.
a) croupous;
b) serous;
c) purulent;
d) fibrinous;
e) gangrenous.
5.3. CHRONIC (PROLIFERATIVE, PRODUCTIVE) INFLAMMATION
Chronic inflammation develops in- neutrophil leukocytes, the chronic in-

dependently or appears through chroni- flammation is mediated by mononuclear
cization of unresolved acute inflammati- cells with nonsegmented nucleus. It is a
on. The main pathogenetic mechanisms productive (proliferative) inflammation,
are the following: where the multiplying (proliferation)
²² persistence of acute inflammation and cell transformation processes pre-
(for example, in slow-developing vail. The morphological substratum of
bacterial pneumonia); the chronic inflammation is the cellu-
²² persistence of pathogenic agent lar inflammatory infiltrate – diffuse or
due to impossibility of its rapid focal mononuclear cell agglomeration.
elimination through phagocytosis; The most frequently encountered are

²² long–lasting action of harmful mononuclear phagocytes (macrophages,
factors (smoking); epithelioid cells), lymphocytes, mul-
²² foreign bodies (for example, inha- tinucleated giant cells and fibroblasts.
lation of dust in pneumoconiosis); Leukocytes, especially eosinophils (in
²² autoimmune diseases; allergic inflammations), are rarely met.
²² diseases of unknown etiology, Classification:
such as Crohn disease, nonspesific ²² interstitial inflammation;
ulcerative colitis, sarcoidosis etc. ²² granulomatous inflammation;
Morphologically, as opposed to acu- ²² polypoid inflammation (with
te inflammation, which is mediated by polyps formation).
5.3.1. INTERSTITIAL INFLAMMATION
It is a type of productive inflamma- myocardium, kidneys, lungs, liver (name

tion, where the inflammatory process is – interstitial myocarditis, nephritis, pneu-
lodged in the stroma (interstitium) of monia, hepatitis).
parenchymatous organs. Morphology: infiltrates, constituted
Most common lodging spots are in of lymphocytes, monocytes, macropha-

ges, plasmocytes and fibroblasts are ob- les, rubella), bacterial infections (scarlet
served in the interstitial tissue of the or- fever, exanthematic typhus, meningo-
gans (Fig. 5–28, 5–29 and 5–30); cellular coccal infection), sepsis.
infiltration is more pronounced around Consequences: fibrosis, sclerosis
vessels (perivascular). and cirrhosis of organs (Fig. 5–31).
Etiology: viral infections (flu, meas-
Fig. 5–28. Interstitial myocarditis (hemato- Fig. 5–31. Postmyocarditic cardiosclerosis (he-
xylin–eosin stain; ×70). matoxylin–eosin stain; ×70).
Fibrosis – connective tissue proli-
feration without organ’s induration (for
example, pneumofibrosis, myofibrosis).
Sclerosis – connective tissue proli-
feration resulting in diffuse or local in-
duration of the parenchymatous organs
(cardiosclerosis, pneumosclerosis, ne-

phrosclerosis).
Cirrhosis – connective tissue pro-
liferation, inducing pronounced defor-
mation of organs (liver, lung and kidney
Fig. 5–29. Productive vasculitis in polyarteritis
nodosa (hematoxylin–eosin stain; ×70). cirrhosis).
It is a type of productive inflammati-
on, characterized by formation of nodu-
les of dense consistency in organs, called
granulomas.
The granuloma is a focal cellular
inflammatory infiltrate; usually it has a
round or ovoid shape, a diameter of 1–2
mm up to 3–5 cm.
The structure of granuloma: in the
center – necrosis focus (detritus, tissu-
lar debris), where the pathogenic agent
can be; at the periphery – a cellular belt,
Fig. 5–30. Interstitial pneumonia (hemato- surrounding the focus of necrosis, con-

5.3.2. GRANULOMATOUS INFLAMMATION
stituted of monocytes, lymphocytes and tic typhus, tularemia, brucellosis, visceral
their derivatives (macrophages, epitheli- fungi, parasitic diseases (echinococcosis,
oid cells, giant cells, plasmocytes). trichinellosis, cysticercosis, toxoplasmo-
Granuloma types, according to cellu- sis), in rheumatic diseases (Fig. 5–32 a, b);
lar composition:
²² macrophagic;
²² epithelioid cell;
²² gigantocellular.
The granuloma cells are of hemato-
genic (bone marrow) etiology. Epitheli-
oid cells differ from normal macropha-
ges by more abundant cytoplasm, filled
with vacuoles and lysosomes, and lower
phagocytic activity. They adhere closely
to one another, reminding the spinous a
layer of the epidermis, hence the name.
Being stable cells, arranged compactly in
the structure of granulomas, they form a
cellular belt that isolates the lesion focus
and the pathogenic agent. The multinu-
cleated giant cells subdivide into “foreign
body cells” and Langhans cells; they are
formed by fusion or incomplete divisi-
on of epithelioid cells or of macropha-
ges. The giant cells may have a diameter b
up to 150 µ and can contain up to 200

nuclei. In the giant foreign body cells, Fig. 5–32 a, b. Granulomatous inflammation
nuclei are distributed chaotically in the of endo- and myocardium in rheumatism (As-
cytoplasm, and in Langhans cells – uni- choff bodies) (hematoxylin–eosin stain; ×70
formly, along the cell membrane in the and ×110).
form of a crown or horse shoe. II – non-infectious granulomas,
Etiology. The granulomas appear for example, in pneumoconiosis, foreign
when the pathogenic agent is resistant bodies, suture material (Fig. 5–33), oily
to phagocytosis and remains in the in- substances etc.
flammatory focus for a long time. By
granuloma formation, the isolation of
harmful factor is produced, its delimita-
tion from the rest of tissue/organ. The
gradual degradation and elimination of
pathogenic agent occur under the influ-
ence of granuloma cells.
The granulomatous inflammation is
observed in more than 70 diseases (gra-
nulomatous diseases).There are:
Fig. 5–33. Foreign body granuloma (suture gra-
I – infectious granulomas, for
nuloma) (hematoxylin–eosin stain; ×70).
example, in typhoid fever, exanthema-

III – granulomas of unknown ori-

gin, for example, Crohn’s disease (Fig.
5–34), sarcoidosis.
Most common consequences of
granulomas:
a) resorption of cellular infiltrate;
b) organization;
c) encapsulation;
d) calcification (petrification);
e) ossification;
f ) secondary necrosis. Fig. 5–34. Epithelioid cell granuloma in the co-
lon in Crohn’s disease (hematoxylin–eosin sta-
in; ×70).
5.3.2.1. SPECIFIC GRANULOMATOUS INFLAMMATIONS
The specific inflammation differs 3) primary or secondary caseous ne-
from ordinary (nonspecific) inflamma- crosis of the altered tissue (pri-
tion by: mary necrosis appears at the ini-
1) the formation of characteristic tial penetration of the pathogenic
granulomas, which enable the agent, and secondary necrosis is
morphological diagnosis of the preceded by exudative or prolife-
respective disease without identi- rative reaction).
fication of the pathogenic agent; Etiology: tuberculosis, syphilis, le-
2) undulate chronic evolution; prosy, rhinoscleroma.
5.3.2.2. TUBERCULOUS GRANULOMATOUS INFLAMMATION

Causative agent – mycobacterium (macroscopically, the necrotic masses

tuberculosis or Koch’s bacillus. resemble the dry cheese); around the
Structure (Fig.5–35 and 5–36): in necrosis focus – a belt of cells arran-
the centre – an amorphous, eosinophi- ged from the centre to periphery, in the
lic, caseous necrosis area, with no nuclei following order: immediately around
Fig. 5–35 and 5-36. Tuberculous granulomas in the lung (hematoxylin–eosin stain; ×70): focus of
caseous necrosis, epithelioid cells, Langhans cells and lymphocytes.

necrosis, there are epithelioid cells with of lymphoid cells (small lymphocytes),
elongated, pale, radially arranged nuclei; among which macrophages and plasmo-
giant multinucleated Langhans cells cytes can be seen at the granuloma pe-
with eosinophilic cytoplasm and nuclei riphery. The tuberculosis nodules vary
arranged in a crown or horseshoe form from the size of a millet grain in mili-
are observed among them; the Lan- ary tuberculosis (Fig. 5- 38 and 5–39) to
ghans cells are typical for tuberculosis; bigger formations of few centimeters in
phagocytosed Koch bacilli can be found diameter. They can be lodged in all tis-
in their cytoplasm (Fig. 5–37a, b); a layer sues and organs.
a b
Fig. 5–37: a - Giant multinucleated Langhans cell (hematoxylin–eosin stain; x280); b - phagocyto-
sis of mycobacterium tuberculosis (Ziehl-Neelsen stain; ×110).
Fig. 5–38. Pulmonary miliary tuberculosis. Fig. 5–39. Miliary tuberculosis of the liver.
Consequences of tuberculous gra- capsulation, petrification, ossification of

nuloma: inflammatory focus;
I – in cases with favorable evoluti- II – in cases with unfavorable evolu-
on (tuberculostatic treatment, high body tion: secondary caseous necrosis.
resistance): resorption, organization, en-
5.3.2.3. SYPHILITIC (LUETIC) GRANULOMATOUS INFLAMMATION

Causative agent – pale treponema. infection. They may have nodular or
Lesions that are specific for syphilis ap- diffuse character and manifest themsel-
pear in the tertiary period of the disea- ves morphologically by the formation of
se, which develops over 3–6 years after granulomas in organs and tissues, called

syphilitic gummas or gummous infiltrates. becomes sticky, resembling the Arabic

Syphilitic gummas can be solitary gum (hence the name of gumma, from the
or multiple; location – visceral organs Greek kommi – gum, rubber).
(liver, heart, kidneys), brain, teguments, Microscopically: necrosis focus in the
soft tissues, bones, cartilages, nasal sep- centre surrounded by a cellular crown,
tum etc. Gummas diameter varies from consisting mainly of lymphocytes,
1 to 5–6 cm (Fig. 5–40 a). Structure: plasmocytes and epithelioid cells; single
well–delimited nodule of grey–pink co- giant Langhans cells are met, which are
lor with elastic consistency. Necrosis and not typical for luetic inflammation (Fig.
softening of the preexistent tissue occurs 5–40 b). The blood vessels are stored at
in the centre of the gumma; this area the gumma’s periphery, where a produc-
In
N
a b
Fig. 5–40 a, b. Syphilitic gummas in the liver: a – macroscopic aspect; b – microscopic pattern
(picrofuchsin van Gieson stain; ×70): N – necrosis, In – predominantly lympho-plasmocytic in-
flammatory infiltrate, H – adjacent hepatic parenchyma.
tive inflammation (proliferative endo-

perivasculitis) is observed. The syphili-
tic gumma consequences: organization,
cicatrization, petrification. Sclerosis and
cirrhosis with severe deformation of or-
gans develop in parenchymatous organs,
for example: macronodular liver cirrho-
sis (hepar lobatum).
Gummous infiltrates are lympho-
plasmocytic agglomerations of different
dimensions in aorta (Fig. 5–41), myo-
cardium, liver, bones, joints and other Fig. 5–41. Syphilitic mesaortitis, cell infiltrates
organs. The aorta is involved in 80–85% in the aortic media, around the vasa vasorum
of patients with tertiary syphilis; the as- (hematoxylin–eosin stain; ×70).
cendant portion, arch and aortic valves tic membranes, decreased elasticity and
are affected. The productive inflamma- aneurysm. Complications and death ca-
tion of vasa vasorum from adventitia and uses: severe cardiac insufficiency due to
aortic media (syphilitic aortitis) deve- aortic valvular insufficiency or aneurysm
lops, which leads to destruction of elas- rupture.

5.3.2.4. LEPROUS GRANULOMATOUS INFLAMMATION
Causative agent – mycobacterium le- represent macrophages, with huge quan-

prae or Hansen bacillus. Location of in- tities of mycobacteria in their cytoplasm,
flammatory lesions: skin, subcutaneous which are arranged compactly, like ciga-
tissue, upper respiratory tract, peripheral rettes in a box. The granuloma is situated
nerves. in the skin thickness (in dermis) and is
The specific leprous granuloma – le- separated from epidermis by a defined
proma appears in the lepromatous form area of connective tissue (Fig. 5–42 a, b).
of the disease. Structure: the leproma is Macroscopically, lepromas have the
composed of macrophages, lymphocytes, appearance of nodules of different di-
plasmocytes and giant cells with foamy mensions, lodged in the skin.
(vacuolated) cytoplasm generated by li- Consequences: lepromas can ne-
pid inclusions – the so–called leprous crotize, and later they organize and
cells (leprous globes or Virchow cells). The form mutilating scars, which deform the
latter are characteristic for leprosy and patient’s exterior aspect (“leonine facies”).

a b
Fig. 5–42 a, b. Leprous granuloma in the skin: a – leprous granuloma (hematoxylin–eosin stain;
×70), b – Virchow cells (Ziehl-Neelsen stain; ×110).
5.3.2.5. GRANULOMATOUS INFLAMMATION IN RHINOSCLEROMA
Causative agent – Frisch bacillus. In- adjacent tissues of the superior lip.
flammatory process location: mucosa of Microscopically, one observes pro-
the upper respiratory tract, especially the ductive inflammation with formati-
nasal cavity. on of some granulomas, constituted
Macroscopically, it manifests itself from plasmocytes, epithelioid cells and
by proliferation of granulation tissue lymphocytes; the presence of big ma-
of dense consistency, with narrowing crophages with foamy, clear cytoplasm
or obliteration of the respiratory tract; - Mikulicz cells - is characteristic (con-
the inflammatory process can infiltrate tain many Frisch bacilli), as well as the

presence of Russel corpuscles (hyali-

ne spheres), which appear as a result of
dystrophic modifications of plasmocytes
(Fig. 5–43).
Consequences: sclerosis and hyali-
nosis of the granulomatous tissue. Pos-
sible complications: respiratory distur-
bances (asphyxia).
Fig. 5–43. Rhinoscleroma in the nasal mucosa, inflammatory infiltrate with Mikulicz cells and
plasmocytes (hematoxylin–eosin stain; ×110)
5.3.3.6. PRODUCTIVE INFLAMMATION WITH POLYP FORMATION

Polyps are formations with smooth polyps of inflammatory origin are called
or papillary surface, with the dimensions hyperplastic polyps. They develop on
from 1–2 mm to some cm; they can be the background of some chronic inflam-
single or multiple, some of them have a matory processes of respective mucosae,
cauliflower aspect. Location – mucous for example, gastritis, endocervicitis,
membranes covered with glandular epi- endometritis, enterocolitis and chronic
thelium of stomach (Fig. 5–44), intes- rhinosinusitis. Microscopically, they are
tine (Fig. 5–45 a, b), uterus and cervi- formed of tortuous, cystically dilated
cal canal (Fig. 5–46 a, b), nasal meatus glands, which contain mucus; the stro-
(Fig. 5–47 a, b, c), bronchi, trachea. The ma is edematous, hyperemic, infiltrated
a b
Fig. 5–44 a, b. Gastric polyps: a – macroscopic aspect; b – microscopic pattern (hematoxylin–eosin
stain; ×50).
a b
Fig. 5–45 a, b. Colonic polyp: a – macroscopic aspect; b – microscopic pattern (hematoxylin–eosin
stain; ×50).

a b
Fig. 5–46 a, b. Cervical canal polyp: a – macroscopic aspect at colposcopic examination; b – micro-
scopic pattern (hematoxylin–eosin stain; ×50).

b c
polyps have a large number of eosino-

phils in the inflammatory infiltrate, as a
manifestation of allergic inflammation
(allergic rhinitis).
Complications: hemorrhages, second-
ary inflammation, circulatory distur-
bances, stenosis of the lumen of tubular
or hollow organs. Hyperplastic polyp
a malignization is observed very rarely.
Papillary formations covered with
Fig. 5–47 a, b, c. Nasal polyp: a – macroscopic stratified squamous epithelium, called
aspect; b, c – microscopic pattern (hemato- condyloma acuminata (Greek kondylos
xylin–eosin stain; ×40 and ×70). – prominence, Latin acumen - tip) can be
met on the mucosae covered with strati-
with lymphocytes, macrophages and
fied squamous epithelium and on the
plasmocytes. There are groups of blood
skin. They are located on the skin of the
vessels with sclerosed, thickened walls
perineal area, cervical or urethral mu-
in the area of polyp’s pedicle. The nasal
cosa. They are caused by human papil-

loma virus (HPV). The irritant action of with perinuclear halo (clear area), which
the urogenital secretions in gonorrhea, appear under the influence of HPV, is
syphilis and other venereal diseases is characteristic. Chronic inflammatory
important. Microscopically, the pres- infiltration is observed in the connective
ence of koilocytes – intermediary cells stroma of acuminate condylomas.
of the stratified squamous epithelium
ESSENTIAL TERMS
on the subject: “CHRONIC (PROLIFERATIVE, PRODUCTIVE) INFLAMMATION”
cirrhosis Langhans cell scleromatous granuloma

condyloma acuminatum leproma sclerosis
epithelioid cell mesaortitis secondary necrosis
fibrosis Mikulicz cell specific granuloma
foreign body cell nonspecific granuloma suture granuloma
foreign body granuloma primary necrosis syphilitic gumma
granuloma polyp tuberculous granuloma
interstitial inflammation Russel corpuscle Virchow cell
TESTS
on the subject: “CHRONIC (PROLIFERATIVE, PRODUCTIVE) INFLAMMATION”
SET I.
Multiple-choice questions with one cor- hyperergic inflammatory reacti-
rect answer. on;
1. Which is the characteristic morphologic sub- e) can transform into multinuclea-
stratum of the productive inflammation: ted giant cells.

a) serous fluid; 4. What cells from those listed below are epi-
b) abscess; thelioid cell forerunners:
c) cellular infiltrate; a) neutrophil leukocytes;
d) necrosis; b) eosinophils;
e) cystic cavity. c) platelets;
2. What cells prevail in the inflammatory d) macrophages;
infiltrate in the final inflammation stage: e) T lymphocytes.
a) leukocytes; 5. The following microscopic aspects are ele-
b) fibroblasts; ments that characterize tuberculous in-
c) sideroblasts; flammation, with the exception of:
d) monocytes; a) presence of epithelioid cell gra-
e) T lymphocytes. nulomas;
3. What is the correct statement referring to b) evolution of granulomas to ca-
plasmocytes: seous necrosis;
a) derive from B lymphocytes; c) presence of Langhans cells;
b) can transform into macrophages; d) recent abscess formation;
c) the endoplasmic reticulum is e) specific stains reveal Koch ba-
hardly seen; cillus.
d) it accumulates in the areas of

SET II.
Multiple-choice questions with 2, 3 or 3) Which of the listed signs characterize the
more correct answers. specific inflammation:
1) The characteristic signs of chronic in- a) acute evolution;
flammation: b) formation of exudate;
a) long time evolution; c) formation of granulomas;
b) mononuclear infiltration of tis- d) undulant chronic evolution;
sue; e) presence of a specific infectious
c) sclerotic lesions in the inflamma- agent.
tory focus; 4) Which of the listed cells are observed in the
d) secondary necrosis of tissue; tuberculous granuloma:
e) predominance of the exudative a) epithelioid cells;
reaction. b) lymphocytes;
2) Morphogenetic stages of granuloma: c) mastocytes;
a) accumulation of neutrophils; d) foreign body giant cells;
b) accumulation of young monocy- e) Langhans cells.
tic phagocytes; 5) The microscopic signs characteristic for
c) formation of macrophage granu- syphilitic gumma:
loma; a) necrosis;
d) formation of epithelioid cell gra- b) lymphocytes;
nuloma; c) Mikulicz giant cells;
e) accumulation of lymphocytes. d) neutrophils;
e) plasmocytes.
SET III.

The classification tests include 2–4 sub- I – acute inflammation;
jects and a series of answers. Indicate which II – chronic inflammation;
answers are correct for each separate sub- a) predominance of the productive
ject. tissular reaction;
1. Which of the listed pathologic processes re- b) rapid elimination of the patho-
fers to: genic agent and recovery of alte-
I – exudative inflammation; red tissues;
II – productive inflammation; c) intense exudative reaction;
a) gastric polyps; d) poorly pronounced exudative re-
b) renal abscess; action;
c) interstitial pneumonia; e) diffuse or focal mononuclear in-
d) rheumatic granulomatous myo- filtration of tissues;
carditis; f ) prevalence of tendency towards
e) diphtheritic croup; sclerosis.
f ) villous heart; 3. Which of the listed inflammation variants
g) gummous mesaortitis; refer to:
h) appendicular empyema. I – ordinary inflammation;
2. Which of the listed signs characterize the: II – specific inflammation;
a) inflammation in tuberculosis;

b) interstitial nephritis; morphologic process:

c) polyps; I – sclerosis;
d) syphilitic inflammation; II – necrosis;
e) rhinoscleromatous inflammati- III – cirrhosis;
on. IV – encapsulation;
4. Which of the listed cells belong to: V – inflammatory infiltrate.
I – monocytic series; a) excessive proliferation of the
II – lymphocytic series; connective tissue with deforma-
a) epithelioid cells; tion of the organ;
b) plasmocytes; b) excessive proliferation of the
c) multinucleated giant cells; connective tissue with densifica-
d) natural killer cells; tion of the organ;
e) circulating macrophages; c) cellular death;
f ) tissular macrophages; d) cell agglomerations in the in-
g) cytotoxic cells. flammatory focus;
e) connective tissue proliferation
5. Choose the correct definition for each
around a lesion focus.
Daily practice cases are presented with B) What kind of consequences can de-
clinical and morphological data from clini- velop in the patient?
cal histories and/or from necropsy protocols. a) postmyocarditic cardiosclerosis;
Each subject includes simple or multiple - b) atherosclerotic cardiosclerosis;
answer questions, with 1, 2 or more correct c) postinfarction cardiosclerosis;
answers. d) ischemic cardiosclerosis;
e) hypoxic cardiosclerosis.
1. A 36-year-old patient with unclear car- C) What complications may develop:
diac pathology had a myocardium biop- a) heart rupture;
sy. The microscopic examination revealed b) cardiac insufficiency;
mononuclear inflammatory infiltration of c) arrhythmias;
lymphocytes, histiocytes, plasmocytes, fibro- d) cardiac aneurysm;
blasts. e) sudden death.
2. A 24-year-old patient complains of fever,
Questions:
weakness, inappetence. The biopsy of a su-
A) What is the diagnosis resulted from praclavicular lymph node was collected.
the microscopic pattern: The histological test revealed the presen-
a) serous myocarditis; ce of granulomas with caseous necrosis in
b) granulomatous myocarditis; the centre and a cellular belt of epithelioid
c) septic myocarditis; cells, multinucleated giant Langhans cells
d) purulent myocarditis; with nuclei arranged in crown-form and
e) interstitial myocarditis. lymphocytes.

Question: presence of lymphocytes, plasmocytes, Mi-
Which pathogenic agent must be identi- kulicz cells, Russel corpuscles in granulo-
fied in order to confirm the diagnosis: mas.
a) Frisch bacillus; Question:
b) Hansen mycobacterium;
What is the diagnosis in this case, taking
c) Koch mycobacterium;
into consideration the described morpho-
d) pale treponema;
logic pattern:
e) actinomycetes.
a) rhinoviral rhinitis;
3. The necropsy revealed a round formati- b) adenoviral rhinitis;
on with a diameter of 1,5 cm in the liver, c) rhinoscleroma;
which, examined microscopically, had the d) meningococcal nasopharyngitis;
following structure: in the centre - necro- e) allergic rhinitis.
tic masses, and around them - granulation
5. The biopsy collected from the bronchial wall
tissue with plasmocytes, lymphocytes, single
of a patient with chronic bronchitis revea-
giant Langhans cells and blood vessels with
led proliferations of the granulation tissue
the signs of endo– and perivasculitis.
over mucosa; the granulation tissue is di-
Question: ffusely infiltrated by lymphocytes, histiocytes
What is the diagnosis in this case, taking and plasmocytes, covered with glandular
into consideration the described morpho- epithelium in some areas.
logic pattern: Question:
a) tuberculous granuloma;
Which type of bronchitis is in this case:
b) leprous granuloma;
a) catarrhal–mucous chronic bron-
c) syphilitic gumma;
chitis;
d) rhinoscleromatous granuloma;
b) purulent chronic bronchitis;
e) actinomycotic granuloma.
c) polypoid chronic bronchitis;
4. A 58-year-old patient was complaining of

d) deformed chronic bronchitis;
difficult nasal respiration, dyspnea. During e) mucopurulent chronic bronchi-
the clinical examination, the otorhino- tis.
laryngologist found thickening of the nasal
mucosa. The biopsy of the nasal mucosa re-
vealed granulomatous inflammation with

Chapter 6 IMMUNOPATHOLOGIC PROCESSES
IMMUNOPATHOLOGIC PROCESSES
Immunopathologic processes are de- The immune response may be of

termined by the function disorder of the cellular or humoral type and it manifests
immunocompetent (lymphoid) tissue. itself morphologically by proliferation
The immune reactions, which normally and differentiation of the cells of central
have a body defense function against or peripheral organs of the lymphoid
various foreign antigens, can lead to al- system. Primarily, the character of the
terations of own tissues, during these immune reaction depends on the pecu-
processes. Immune reactions exercise, liarities of the antigen, its quantity, the
in such conditions, a harmful action on way of penetration into the organism,
tissues, more serious than the antigens previous contacts with the respective
themselves. immunogenic antigen.
The organs of the immunocompe- The immune reaction of humoral
tent system are subdivided into central type is triggered at the penetration into
organs: a) thymus and b) bone marrow the body of different soluble (dissolved)
and peripheral organs: a) lymph nodes, antigenic substances, for example, of mi-
b) spleen, c) lymphoid tissue associa- crobial toxins, extracellular pathogenic
ted with the digestive tract mucosa – agent (bacteria). Its essence lies in anti-
MALT (mucosa-associated lymphoid tis- gen destruction by the specific antibody
sue): pharyngeal ring, lymphoid follicles produced by plasmocytes, whose prede-
from stomach mucosa, Peyer patches, cessors are B lymphocyte. The antigen-
vermicular appendix, solitary follicles of antibody complex is phagocytized by
the large intestine; d) lymphoid tissue macrophages and eliminated from the
associated with bronchi and skin (BALT organism; the process is called immune
and SALT – bronchi and skin – associated phagocytosis. Thus, the effector cell in
lymphoid tissue), e) lymphoid tissue from humoral immune reaction is plasmocy-
exocrine glands (salivary glands, pancre- te (Fig. 6–1a).
as) and mammary gland. In case of penetration into the or-
Three cellular populations par- ganism of some antigens of cellular
ticipate in the immune reactions: a) (tissular) origin, for example foreign
T lymphocytes (T-dependent), b) B bodies, pathogenic agents which para-
lymphocytes (B-dependent) and c) ma- sitize intracellularly (especially viruses
crophages. and fungi), an immune reaction of cellu-

IMMUNOPATHOLOGIC PROCESSES Chapte r 6
a b
Fig. 6–1 a, b. Schematic representation of immune reactions: a) humoral, b) – cellular : B – B-

lymphocyte, T – T-lymphocyte, Th – T-helper lymphocyte, Ts – T–suppressor lymphocyte, Tk
– T–killer lymphocyte (cytotoxic), M – macrophage, Ag – antigen, Ab – antibody, Pl – plasmocyte.
lar type develops, whose essence lies in

antigen destruction by sensitized T- kil-
ler lymphocyte with the help of macro-
phages, without participation of antibo-
dies – immune cytolysis (cytolytic and
cytopathic action of lymphocytes). The
effector cells in the cellular immune re-
action are the T – killer lymphocytes
and macrophages (Fig.6–1b).
Each type of immune reaction inclu-

des 3 consecutive stages: afferent stage –
Fig. 6–2. Hyperplasia of lymph node follicles in information transmission to the specific
antigenic stimulation (hematoxylin–eosin sta- reactive cells, central stage – proliferati-
in; ×70). on and differentiation of the lymphatic
system cells (blastic transformation of
B or T-lymphocytes, the appearance of
plasmocytes, T lymphocytes sensitizati-
on) and the efferent stage – the reaction
of specific antibodies and T-lympho-
cytes sensitized with the antigen.
Morphological changes, which occur in
the lymph nodes and spleen at antigenic
stimulation, are nonspecific, stereotyped.
Macroscopically, these organs are incre-
ased in volume, edematous, hyperemic;
microscopically, one notices a hyper-
Fig. 6–3. Hyperplasia and plasmatization of plasia of immunocompetent cells, trans-
lienal follicles in antigenic stimulation (hema- formation of small lymphocytes in blas-
toxylin–eosin stain; ×70). tic cells (Fig. 6–2, 6–3).

Depending on the type of immu- peripheral organs. The distribution of

ne reaction, hyperplastic processes take thymus-and bursa-dependent areas is
place in different areas of lymphoid presented in Table 6.1.
Table 6.1.
Distribution of thymus-and bursa-dependent areas
Organ Bursa-dependent areas Thymus-dependent areas
Cortical layer Paracortical layer

Lymph nodes
Medullar layer
Peripheral areas of lymphatic Paraarterial area (around the
Spleen
follicles centrofollicular artery)
Interfollicular subepithelial
Tonsils Tonsil follicles
lymphoid areas
Intestinal Interfollicular subepithelial
Intestinal follicles
lymphoid tissue lymphoid areas
The hyperplasia of B–lympho- development reflect the intensity degree

cytes and lymphoblasts, the plasmab- of immunity, the level of development of
lastic and plasmocytic transformation plasma cell antibodies, and, respective-
of B-lymphocytes and proliferation of ly, the antibody titer in blood plasma.
macrophages take place in bursa-de- In the immune reaction of cellu-
pendent areas, at the onset of humoral lar type, the blastic transformation of
immune reaction. The hyperplasia of small lymphocytes is not produced in

T-lymphocytes (their activation or sen- the germinal centers of follicles, but
sitization) and macrophages takes place in the paracortical areas of the lymph
in thymus-dependent areas, during the nodes and in the periarterial areas of
immune reaction of cellular type. These splenic follicles. Macroscopically, the
hyperplastic processes are more obvi- spleen is enlarged and has a mottled
ous in regional lymph nodes in relation appearance with multiple whitish foci,
with the place of antigen penetration. which represent hyperplastic lymphat-
The induction of antibody development ic follicles with germinal centers. In
in humoral immune reaction associ- cases of massive and prolonged an-
ates with appearance of germinal cen- tigenic stimulation, these hyperplas-
ters (clear centers) in the follicles of the tic processes are more pronounced.
spleen and lymph nodes – the so-called Immunopathies can be divided into
secondary follicles (follicles with germi- four groups:
nal centers), where the lymphoblastic 1) thymus lesions;
proliferation takes place. These follicles 2) hypersensitivity (hypersensibility)
are formed around the macrophages that reactions;
contain antigen. The appearance of sec- 3) autoimmune diseases;
ondary follicles and the extent of their 4) immunodeficiency syndromes.

6.1. LESIONS OF THE THYMUS
In some cases, they constitute the It is observed in children in severe

consequence, in others - the cause of infectious diseases, malignant tumors
immunological homeostasis disturbance. with metastases, leukemias, traumatisms
The appearance of some immu- and different severe stressful situations,
nodeficiency syndromes, autoimmune when rapid elimination of corticostero-
diseases and endocrine disturbances is ids by the adrenals and massive antigenic
related to thymus pathology. stimulation of the immune system occur.
Accidental or stress thymic involution The glucocorticoid hormones have the
capacity to induce thymus apoptosis.
Macroscopically, a rapid decrease of
The longer and more severe is the basic
thymus mass and volume is observed
disease, the more evident is the involu-
(8–10 times in several days). The histolo-
tion extent of the thymus. If the disease
gical examination reveals smaller thymus
evolution is not too long, the thymus can
lobules, thinned and poor in lymphocytes
recover.
cortical layer, as a consequence of their
The possible consequences of
progressive destruction. Lymphocyte
thymus accidental involution:
karyorrhexis, their active phagocytosis
a) regeneration of thymus;
by macrophages, colabation (collapse) of
b) atrophy of thymus.
reticular epithelium, dystrophic calcino-
The thymus accidental involution
sis and appearance of some cystic cavi-
can be reversible, as the thymus has a
ties in Hassal corpuscles take place. The
high regenerative capacity, but in acute
characteristic sign – equivalence or even
infectious diseases, bacterial and viral,
inversion of thymus lobule layers, accor-
purulent process infections or malignant
ding to lymphocyte content, the contrast

tumors with metastases, it can lead to
between them disappears, as a result of
acquired thymus atrophy. The clinical–
cortical T-lymphocyte depletion; the
functional importance of thymus acci-
content of lymphocytes in the medullar
dental involution lies in the decrease of
layer can turn higher than that of the
intensity of cellular and humoral immu-
cortical layer (Fig. 6–4).
nity, due to decrease of thymic hormone
secretion.
The atrophy of the thymus –
thymus decrease in mass and size. It is
a consequence of accidental involution
and represents the morphologic substra-
tum of the acquired immunodeficiency.
The hyperplasia of the thymus
– thymus enlargement, due to some
hyperplastic processes. It develops as a
Hodgkin’s lymphoma chemotherapy
complication, in massive thermal bur-
Fig. 6–4. Accidental thymic involution (hema- nings, after corticosteroid treatment
toxylin–eosin stain; ×70). cease in children. The thymus structure

is kept. The morphologic substratum of

immunity decrease in children is to be
considered.
Thymic lymphoid hyperplasia is a
particular form. It is increased in size,
infiltrated with B-lymphocytes and
plasmocytes; lymphoid follicles with
germinal centers appear in the medul-
lar layer of the thymic lobes, a fact that
is not seen in normal conditions. It is
observed in autoimmune diseases, for Fig. 6–5. Thymic hypoplasia in the combined
example, in myasthenia gravis, dissemi- immunodeficiency syndrome (hematoxylin–eo-
nated lupus erythematosus, rheumatoid sin stain; ×70).
arthritis, scleroderma, thyrotoxicosis etc. These pathologic processes repre-
Thymic agenesis (aplasia) - the sent development vices, which often
thymus is absent or persists in the rudi- associate with congenital malformations
ment embryonic state. and manifest themselves clinically as
Hypoplasia is incomplete thymus cellular or combined congenital immu-
development. Macroscopically, the nodeficiency. It is usually associated
thymus is small, the lobules have dimi- with hypoplasia of the lymphoid tissue
nished dimensions, the lymphocyte con- in the lymph nodes and spleen, where
tent is reduced considerably, the cortical the preponderant atrophy of thymus-
layer is atrophied; an insignificant num- dependent areas is observed. It manifests
ber of small Hassal corpuscles is obser- itself clinically by organism’s incapacity
ved in the medullar layer, lacking com- to trigger cellular and humoral immu-
pletely in some places; the interlobular ne reactions. Children are predisposed
connective tissue trabeculae are thicke- to infectious diseases that are recurrent
ned (Fig. 6–5). The secretion of thymic and develop severe complications (pne-
hormones is decreased or abolished. umonia, septicemia). Concomitantly,
Dysplasia – the structure of the malignant mesenchymal tumors are
thymus is altered, the lymphocyte con- frequently observed.
tent is reduced.
6.2. HYPERSENSITIVIT Y REACTIONS
The humoral or cellular immune The main pathogenic factors, which

reaction to both endogenous and ex- favor these reactions, are:
ogenous antigens can cause certain a) allergen’ s prolonged (repeated)
local lesions of the tissues. These reaction;
actions are called hypersensitivity re- b) allergen overcharge (high doses);
actions or diseases and appear in an c) organism’ s general hyperreacti-
vity;
already sensitized to a peculiar anti-
d) hereditary predisposition to al-
gen organism.
lergy.

The hypersensitivity reactions are of It is observed in patients that react
4 types: to certain antigens (allergens) by abnor-
1) hypersensitivity reaction of imme- mal IgE production, with affinity to
diate type (anaphylactic); mastocytes and basophiles. At the Ag’s
2) cytotoxic and cytolytic reaction, initial penetration, IgE is produced and
mediated by antibodies. The inac- fixed on the surface of mastocytes and
tivation, neutralization or stimula- basophils; at the repeated Ag’s pene-
tion reactions are a variant of this tration, the Ag–Ac reaction determines
reaction; mastocyte degranulation and sudden re-
3) hypersensitivity reaction mediated lease of mediators (histamine, serotonin,
by immune complexes (immune heparin, enzymes, prostaglandins, eosi-
complex diseases); nophilic chemotactic factor etc.), which
4) hypersensitivity reaction media- provoke spasms of the smooth muscu-
ted by T-lymphocytes (cellular or lature of the bronchi, intestine, edema,
delayed hypersensitivity); the gra- mucus hypersecretion, vessels dilatation
nulomatous reaction is a variant of and hyperemia of vessels, increase of
this reaction. vascular permeability, proteolytic tissular
Pathogenetic mechanisms of destructions.
hypersensitivity reactions Morphologically, it manifests itself
Immediate hypersensitivity reacti- through acute immune inflammation
on (type I or anaphylactic) (Fig. 6–6) with edema, fibrinoid intumescences
Fig. 6–6. Schematic representation of the immediate anaphylactic reaction: Ab - antibody, Ag - antigen.

and/or necrosis of the connective tissue It is observed in anaphylactic shock

and vessels, vessel thrombosis, formati- (due to medicins and insects venom),
on of fibrinous or fibrinous–hemorrha- hives (Fig. 6–7), atopic bronchial asth-
gic exudate. These modifications appear ma, allergic rhinitis (Fig. 6–8), hay
in 5–20 min. and have the tendency to fever, Quincke angioneurotic edema,
diminish gradually in 60 min. from the food or drug allergy.
onset of the allergenic substance action.
Fig. 6–8. Allergic rhinitis, edema, myxomatosis,

inflammatory infiltration, predominantly eosi-
Fig. 6–7. Hives, allergic rash. nophilic of nasal mucosa (hematoxylin– eosin
stain; ×70).
Cytotoxic /cytolytic hypersensi- heterogenic cell membranes (trans-

tivity reaction (type II) (Fig. 6–9) fused or own blood cells, transplant
The antibodies develop against the cells).There can be 2 variants:

superficial antigen components of the ØØ cytotoxicity mediated by anti-
Fig. 6–9. Schematic representation of the cytolytic and cytotoxic reaction : Ab - antibody, Ag - anti-
gen, M - macrophage.

bodies (antibody-dependent – ease of the newborn, post transfusion
the Ag–Ac reaction occurs on reactions, autoimmune hemolytic ane-
the surface of target cells, which mia, medicinal cytopenia (agranulo-
are subsequently destroyed by the cytosis, thrombocytopenia), vascular
K-cells (killer) or NK (natural purpura, graft (transplant) rejection re-
killer), or phagocytized by mac- action. Inactivation and neutralization
rophages; or stimulation reactions are a variant of
ØØ cytotoxicity mediated by comple- these reactions, where the development
ment (cascade activation of the of antibodies against some biologically
complement components causes active substances or cell surface recep-
elimination of mediators and ly- tors occurs (Fig.6–10). Two develop-
sis of the target cells). ment mechanisms of these reactions
It is observed in the hemolytic dis- are known:
Fig. 6–10. Schematic representation of the neutralization and inactivation reaction : Ab - anti-
body, Ag - antigen, M - macrophage.
1) inactivation of hormones, en- of gastric mucosa); in some cases, the

zymes (insulin, thyroglobulin, coagu- antireceptor antibodies block the func-
lation factors), toxins (in diphtheria, tional activity of the cells and stimulate
tetanus); it in other cases.
2) alteration of cellular function Examples: insulin-dependent (type
by antireceptor antibodies (antibodies I) diabetes mellitus, myasthenia gravis,
against the receptors for insulin, acetyl- hypothyroidism, thyrotoxicosis, perni-
choline, thyroid-stimulating hormone, cious anemia, coagulopathy.
thyroglobulin, against parietal cells

Hypersensitivity reaction mediated by toxic immune complexes (type III)

or immune complex diseases (Fig. 6–11)
Fig. 6–11. Schematic representation of immune complex reaction : Ab - antibody, Ag - antigen.
The Ag–Ac immune complex in- ses (disseminated lupus erythematosus,

duces the activation of complement rheumatoid arthritis), allergic dermati-
components, basophilic and neutrophil tis, allergic alveolitis („farmer’s” lung).
leukocytes, elimination of inflammation
mediators. The harmful action of toxic
immune complexes can occur in case of:
a. excess of antibodies with in-
flammatory reaction in the place
of antigen’s introduction (Arthus
reaction);
b. excess of antigen with generalized
reaction and lodging of immune
complexes in the basal membranes
of kidney capillaries, joints, skin. Fig. 6–12. Membranous glomerulonephritis,

Examples: serum sickness, glomeru- immune complex deposits on the basement
lonephritis (Fig. 6–12), rheumatic disea- membrane of the renal glomerulus capillary
(electron microscopy; ×10000).
Hypersensitivity reaction mediated by T-cells (type IV or delayed hypersen-
sitivity) (Fig. 6–13)
Fig. 6–13 Schematic representation of the hypersensitivity reaction mediated by T-cells: Tdh –
delayed hypersensitivity T-lymphocytes, Tk - T-killer lymphocyte, M - macrophage.

The immune response appears in Examples: tuberculin type reaction,
24–72 hours or even in 1–2 weeks, rela- contact dermatitis, graft rejection, autoim-
ted to T-lymphocytes and macrophages, mune diseases, tuberculosis, syphilis, hel-
which make the immune cytolytic - tar- minthosis, mycosis. The classic example is
get-cell destruction. The morphological the Mantoux reaction or tuberculin test: at
substratum is lymphocytic and macro- intracutaneous injection of tuberculin in a
phage infiltration. The granulomatous person infected by the tuberculosis bacil-
reactions constitute an alternative, when lus, there appears redness (erythema) and
the isolation and delimitation of the induration in 8–12 hours, reaching max-
pathogenic agent (allergen) take place. imum size (1–2 cm in diameter) in 2–7
Main cellular components of granulo- days. Histologically, perivascular (perive-
mas are epithelioid cells and multinu- nular) infiltration with lymphocytes and
cleated giant Langhans cells (Fig. 6–14). monocytes occurs in the skin.
Fig. 6–14. Schematic representation of the hypersensitivity reaction, granulomatous type: Tdh –

delayed hypersensitivity T-lymphocytes, M - macrophage.
6 . 3 . AU TO I M M U N E D I S E A S E S
Autoimmune diseases are a group 1) organ specific;
of diseases based on the reaction of au- 2) organ non-specific;
toantibodies and sensitized lymphocytes 3) secondary autoimmune disor-
against self-antigens, causing their struc- ders.
tural and functional alterations. Among General characteristic of autoimmune
the most frequent etiologic factors of diseases
self immunization, the most important Organ specific (true) autoimmune dis-
are chronic viral infections, radiation, eases
certain chemical and physical actions, The pathogenetic mechanism con-
both on the immunocompetent organs sists in impairment of physiological
and on the target organs. isolation of organs and tissues towards
According to the mechanism of which there is no immunological tol-
autoimmunization development, three erance, alteration of their histohemat-
groups of autoimmune diseases are dis- ic barriers; the unmodified antigens of
tinguished: these tissues, which are isolated (seques-
tered) immunologically, cause develop-

ment of antibodies and/or sensitization lymphoid follicles with germinal clear

of T-lymphocytes. The causative factors centers (Fig. 6–15a). These infiltra-
are chronic viral infection, trauma, radi- tions substitute gradually the glandular
ation, sunstroke. parenchyma. The thyroid follicles are
It can be found in the Hashimoto’s atrophied; they contain poorly colored
thyroiditis (goiter), disseminated scle- or vacuolated colloid, some of them lack
rosis, autoimmune encephalomyelitis, the lumen, sclerosis processes develop.
sympathetic ophthalmia, autoimmune Macroscopically, the thyroid gland is
orchitis, idiopathic Addison’s disease. enlarged, painless; it has an elastic con-
The most classic example of au- sistency and does not adhere to adjacent
toimmune true disease is Hashimo- tissues (Fig. 6–15b). Clinically, the evo-
to autoimmune thyroiditis or goiter. A lution is accompanied by hypothyroid-
diffuse stroma infiltration with lym- ism and advances towards myxedema.
phocytes and plasma cells is revealed in It is found almost exclusively in women
the thyroid gland, sometimes forming aged between 40–50 years.
a b
Fig. 6–15 a, b. Autoimmune Hashimoto thyroiditis: a – microscopic pattern (hematoxylin–eosin

stain; ×70); b – macroscopic aspect.
Organ nonspecific (systemic) autoim- polyarteritis nodosa, Sjogren syndrome.
mune diseases Development of antibodies against var-
It is a group of diseases with primary ious structural elements of organs and
disorders of immunocompetent system tissues occurs in these diseases.
function. There is loss of lymphocytes Examples:
capacity to distinguish the foreign anti- ØØ in disseminated lupus erythema-
gens from own ones. Morphological le- tosus – antinuclear, antinucleolar,
sions have a general, systemic character. antimitochondrial, anti-erythrocyte,
The most important causative factors anti-thrombocyte, anti- lymphocyte
are: mutations, lymphotropic virus in- autoantibodies etc; the most import-
fections, ultraviolet radiation, drugs etc. ant for diagnosis are the antinuclear
It is observed primarily in the systemic antibodies against the double–strand-
diseases of the connective tissue: dissem- ed DNA. The nuclei of altered cells
inated lupus erythematosus, rheumatoid react with antinuclear auto antibodies
arthritis, systemic scleroderma, derma- and convert into homogeneous cor-
tomyositis, ankylosing spondyloarthritis, puscles, which are stained with he-

matoxylin - hematoxylin bodies (Fig. blood vessels (vasculitis) (Fig. 6–18),
6–16). Such nuclei are phagocytized heart valves (Libman–Sacks endocar-
by neutrophil leukocytes and macro- ditis), synovial membranes of joints;
phages, forming lupus erithematosus ØØ in rheumatoid arthritis – autoanti-
cells (LE–cells) (Fig. 6–17). The im- bodies against Fc fragments of IgG;
mune complexes lodge in the skin (er- immune complex, called rheumatoid
ythema, butterfly-shaped rash on the factor, represents “Ig–anti–Ig”, found
face), kidneys (glomerulonephritis), in blood serum and synovial fluid.
2
a b
Fig. 6–16. Hematoxylin bodies: a – antinuclear antibodies (immunofluorescent reaction); b –
blood smear (azure–eosin stain).
Fig. 6–17. Lupus erithematosus cell, blood Fig. 6–18. Allergic vasculitis, fibrinoid intumes-
smear (azure–eosin stain). cence and cellular infiltration of vascular wall
Mainly, it affects small and medium Secondary autoimmune diseases
size joints; The secondary autoimmunization
ØØ in systemic sclerosis – antinucleolar occurs in the appearance of new, hetero-
autoantibodies are more character- geneous antigens in the body, which may
istic; it affects the skin and visceral lead to suppression of natural tolerance.
organs; The ethiopathogenetic mechanisms:
ØØ in Sjogren syndrome – autoantibod- ØØ protein distortion in burns, irradia-
ies against salivary duct cells; it is man- tion, cold injury, chronic inflamma-
ifested by inflammation, atrophy and tion, viral infections;
sclerosis of salivary and tear glands. ØØ cross–reaction: the appearance of

some bacterial antigens, whose struc- (macrophages, fibroblasts, plasmocytes,

ture is identical with the structure of endotheliocytes etc., which were subject
body tissue (e.g. serological Y type to the action of some mutagenic fac-
– cardial – of beta–hemolytic strep- tors) and the plasmatic component (P)
tococcus has antigenic community – blood plasma proteins and polysaccha-
with cardiomyocyte sarcolemma, and rides. The proteo–polysaccharide com-
the XII serotype – nephritogenic – ponents are closely related to each other
with basement membranes of renal and to elements of the tissue where the
glomeruli, klebsiella – with the lung amyloid is deposited, particularly with
tissue; chondroitin sulfates of the ground sub-
ØØ haptenic mechanism - the necrotic stance of the connective tissue (heparan
products, drugs, toxins acting as hap- sulfate and dermatan sulfate). Fibrillar
tens. proteins constitute 90%, and polysaccha-
Examples: glomerulonephritis, rheu- rides – 10% of the total mass of amyloid.
matism, myocardial infarction, chronic Today, the classification of amyloidosis
gastritis, ulcerative colitis, liver cirrhosis, is adopted according to the biochemical
drug disease, allergic anemia, etc. composition of the amyloid substance.
Group III disorders are not inde- There are more than 20 biochemical
pendent autoimmune diseases, the auto- variants of amyloidosis. The most com-
immune conflict being only a complica- mon and important are the following:
tion of basic morbid process. Secondary 1) AL–amyloidosis (amyloid light
autoimmune disorders result in chroni- chain); the amyloid is composed of light
zation and aggravation of the respective chains of immunoglobulins, synthesized
diseases. by plasma cells. It is found in cases of
Morphologically, the autoimmune monoclonal proliferation of B-lym-
conflict is manifested through target- or- phocytes, most frequently in multiple
gan infiltration with immunocompetent myeloma, which is a malignant tumor

cells (lymphocytes, plasma cells and mac- of plasma cells (plasmocytoma). This
rophages), the appearance of lymphatic form of amyloidosis is considered pri-
follicles with germinal centers, dystro- mary, because it is not preceded by other
phic and necrotic parenchyma lesions, illnesses. It develops in 10–15% of pa-
proliferation of connective tissue stroma. tients with multiple myeloma, but it is
Amyloidosis also found in other B-cell lymphomas.
The disease is characterized by depo- The lesions have a systemic character,
sition of a complex protein substance, affecting mainly the cardiovascular sys-
called amyloid, in various tissues and tem, muscles, nerves, skin.
organs. The name is due to its tincto- 2) AA – amyloidosis associated with
rial properties, similar to starch (Rudolf protein synthesis in the liver –serum
Virchow). The amyloid substance is a precursors of amyloid substance (SAA
glycoprotein, where fibrillar proteins are – serum amyloid associated protein). The
conjugated with polysaccharides. It con- production of this protein is increased
tains two main components: the fibril- in different inflammatory processes.
lar component (F), which is a fibrillar This form of amyloidosis is considered
protein, synthesized by amyloidoblasts secondary (reactive), since it is preceded

by other chronic inflammatory diseases, the main component of senile plaques,
for example, in some chronic infections which are found in Alzheimer disease
(tuberculosis, syphilis, leprosy, dysen- both in the brain substance and in cere-
tery, infective endocarditis, actinomy- bral blood vessels.
cosis, etc.), in diseases accompanied by Morphological characteristics.
chronic purulent processes (suppurative Macroscopically, the affected organs
bronchiectasis, abscesses, osteomyelitis, are enlarged, have a yellow color, dense
suppurated wounds, empyema, chronic consistency, lardy or waxy appearance
septicemia), in rheumatic diseases (rheu- (Fig. 6–19). Initially, the spleen in am-
matoid arthritis and systemic lupus ery- yloidosis has a mottled appearance due
thematosus), in Hodgkin’s disease. It is to the focal amyloid deposits in lymph
a generalized form of amyloidosis, with follicles, reminding of sago beans (it is
predominant damage of the spleen, liver, called sago spleen, Fig. 6–20) and lat-
kidneys, adrenals and intestine. er, as the lesions progress, the process
3) Aβ amyloidosis is found in brain becomes diffuse, homogeneous, the
lesions in Alzheimer disease. The Aβ spleen gains a lardy aspect (lardy spleen,
protein comes from transmembrane Fig. 6–21 a). At optical microscopy, the
glycoproteins, called amyloid precursor amyloid is an amorphous, non-struc-
proteins (Aβ PP – amyloid β precursor tured substance of a homogeneous eo-
protein). The Aβ amyloid constitutes sinophilic color, which lodges extracel-

Fig. 6–19. Renal amyloidosis. Fig. 6–20. Focal amyloidosis of the spleen (sago
spleen).
a b
Fig. 6–21 a, b. Diffuse amyloidosis of the spleen: a – lardy spleen; b– macroscopic Virchow reaction
for amyloid identification.

lularly (Fig. 6–22), and with a fibrillar • basement membranes of glandular

structure at electron microscopy (Fig. structures (tubes, channels, ducts);
6–23). The amyloid substance does not • organ stroma, along reticular or
cause inflammatory reaction. The pre- collagen fibers.
dominant places for amyloid deposits in
various organs are: The main morphogenetic mecha-
• walls of blood and lymph vessels nism of amyloidosis is pathological syn-
(in intima or adventitia); thesis.
Am
M
S
MF
Fig. 6–22. Hepatic amyloidosis (hematoxylin– Fig. 6–23. Amyloidosis of myocardium (elec-
eosin stain; ×70). tron microscopy; ×23000): Am - amyloid, MF
- myofibrils, M - mitochondria, S - sarcolema.
To identify the amyloid substance,
specific methods are used:
²² Virchow macroscopic reaction
– the successive application of
Lugol solution and sulfuric acid

(10%) on sectional area colors the
amyloid into blue–purple or dark
green (Fig. 6–21b).
²² with Congo red, the amyloid
stains into dark red and the re-
maining tissue - into pink-yellow Fig. 6–24. Renal amyloidosis (Congo red stain;
(Fig. 6–24). ×70).
²² with methyl–violet or gentian vi-
olet, amyloid turns red, and the sue or the biopsies of the rectal or oral
other tissular elements turn violet cavity mucosa are used.
(metachromatic stain). The consequences of amyloidosis.
²² with S or T thioflavin - the amy- It is an irreversible process resulting in
loid appears green-yellow at the progressive parenchyma atrophy and
luminescent microscope (ultravio- sclerosis of damaged organs, and, under
let light). the functional aspect, in severe impair-
To make a diagnosis, the aspiration ment or abolition of their function.
biopsy of the subcutaneous adipose tis-

6 . 4 . I M M U N O D E F I C I E N C Y S Y N D RO M E S
The immunodeficiency syndromes noglobulin is normal. Concomitantly,

represent a manifestation of immune there are multiple developmental vic-
system failure, which can be primary es, particularly agenesis of parathyroid
(congenital) or secondary (acquired). glands and severe infectious diseases.
Primary immunodeficiency syn-
dromes
They are caused by development
disorders of the immune system. They
are subdivided into: a) primary com-
bined immunodeficiencies (cellular and
humoral); b) primary cellular immuno-
deficiencies; c) primary humoral immu-
nodeficiency.
Primary combined immunodefi-
ciency syndromes are observed in chil-
Fig. 6–25. Atrophy, fibrosis and lipomatosis of
dren and neonates, being transmitted
thymus in cellular immunodeficiency (hemato-
in the autosomal recessive way. Mor- xylin–eosin stain; ×70).
phologically, thymus and peripheral
lymphoid tissue hypoplasia is observed, Examples: DiGeorge syndrome (thy-
which leads to functional failure of cel- mic hypoplasia or agenesis).
lular and humoral immunity. In chil- Primary humoral immunodeficien-
dren, there is a high frequency of infec- cy syndromes. In children, the bursa-de-
tious diseases and complications that pendent areas of the peripheral lymphoid

have a recurrent evolution and severe tissue are absent. The lymph follicles
complications (pneumonia, meningitis lack or they are much reduced in size in
and septicemia). There are also records lymph nodes, spleen, tonsils, intestine;
malignant mesenchymal tumors, differ- they do not contain germinal centers and
ent developmental vices. plasmocytes (Fig. 6–26, 6–27).
Examples: Swiss-type agammaglobu-
linemia (Glanzmann-Riniker syndrome)
and Louis–Bar ataxia telangiectasia).
Primary cellular immunodefi-
ciency syndromes. In children, there
is a selective T-cell deficiency due to
agenesis or hypoplasia of the thymus
(Fig. 6–5, 6–25) and thymus depen-
dent areas of peripheral lymphoid tis-
sue. The hypoplasia of periarterial areas
of lienal follicles and paracortical lay-
ers of lymph nodes occurs. Clinically, Fig. 6–26. Atrophy, fibrosis and lipomatosis of
there is a severe deficiency of cellular the lymph node in humoral immunodeficiency
immunity but the synthesis of immu- (hematoxylin–eosin stain; ×70).

thymic tumors (thymoma), sar-

coidosis;
²² secondary immunodeficiency in
plasmacytoma (multiple myelo-
ma), Waldenstrom macroglobu-
linemia as a result of pathological
immunoglobulin secretion;
²² secondary immunodeficiency af-
ter the treatment with corticoste-
roids, immunosuppressants, anti-
Fig. 6–27. Absence of lymphoid tissue in the lymphocyte serum, radiotherapy,
vermicular appendix wall (hematoxylin–eosin in thymectomy;
stain; ×70). ²² secondary immunodeficiency is
The paracortical layer of the lymph the main manifestation of AIDS -
nodes, which is a thymus dependent (acquired immunodeficiency syn-
area, persists. An absence or significant drome, which has a viral etiology,
decrease of the content of all immuno- being caused by retrovirus with
globulins or only of certain classes of tropism for T–helper lympho-
immunoglobulins is recorded. There is cytes). There is a severe depression
a high frequency of infectious diseases of cellular immunity. Morpholog-
in children (bronchitis, otitis, skin infec- ically, it is characterized primarily
tions). by generalized lymphadenopa-
Examples: Bruton agammaglobu- thy, opportunistic infections and
linemia related to X chromosome (X– neoplastic processes. The most
linked), selective deficiency of A immu- common infections are with my-
cobacteria (mycobacterium tu-
noglobulin (West syndrome).

Secondary immunodeficiency syn- berculosis), viruses (cytomega-
dromes lovirus, herpes, hepatitis B, etc.),
Secondary immunodeficiency occurs protozoa (Pneumocystis carinii,
more frequently as a complication of toxoplasma) and fungi (Candida,
various diseases or treatment; the mor- hystoplasma and cryptococcus).
phofunctional lesions of the immune Kaposi’s sarcoma, non-Hodgkin
system develop in a secondary way. lymphomas, Hodgkin lympho-
Examples: ma, carcinomas are characteristic
²² secondary immunodeficiency in among tumors.
leukemias, malignant lymphomas,

ESSENTIAL TERMS
on the subject “IMMUNOPATHOLOGIC PROCESSES”
AA amyloidosis cytotoxic/cytolytic reaction immune cytolysis

Aβ amyloidosis delayed–type allergic reaction immune phagocytosis
accidental thymus disseminated lupus
inactivation reaction
involution erythematosus
Hashimoto autoimmune lupus erythematosus
agenesis
thyroiditis cells
organ nonspecific
AL amyloidosis hematoxylin body
autoimmune diseases
organ specific
amyloidosis humoral immunodeficiency
autoimmune diseases
aplasia humoral-type immunity primary amyloidosis
atrophy hyperplasia rheumatoid arthritis
autoimmune disease hypersensitivity rheumatoid factor
cellular secondary amyloidosis
hypersensitivity reaction
immunodeficiency (reactive)
cellular-type
hypoplasia Sjogren’s syndrome
hypersensitivity
cellular-type
immediate anaphylactic reaction systemic sclerosis
immunity
combined
immediate-type allergic reaction Virchow reaction
immunodeficiency
cross immune reaction immune complexes reaction

TESTS
on the subject "IMMUNOPATHOLOGIC PROCESSES "
SET I.
Multiple-choice questions with one cor- diate-type allergic reactions, with the ex-
rect answer ception of:
1) Which immune reaction manifests itself a) it develops in several minutes;
morphologically by expanding germinal b) lymphocytes and macrophages
centers and increasing the number of plas- prevail;
mablasts and plasmocytes: c) sero–hemorrhagic inflammati-
a) cellular-type immune reaction; on;
b) mixed immune reaction; d) fibrinoid necrosis of vascular
c) autoimmune reaction; walls;
d) immunodeficiency reaction; e) vessels thrombosis.
e) humoral-type immune reaction. 3) All the listed signs characterize the dela-
2) All the listed signs characterize the imme- yed-type allergic reactions, with the ex-
ception of:

a) it develops in 24 – 72 hours; c) scleroderma;

b) lymphocytes and macrophages d) Hashimoto thyroiditis;
prevail; e) polymyositis.
c) neutrophil leukocytes prevail; 5) Which of the listed autoimmune diseases
d) granulomatosis; are characterized by antinuclear autoan-
e) interstitial infiltrate. tibodies?
4) Which of the listed autoimmune diseases a) polymyositis;
have a local, organ-specific character: b) scleroderma;
a) disseminated lupus erythemato- c) Hashimoto thyroiditis;
sus; d) systemic lupus erythematosus;
b) rheumatoid arthritis; e) autoimmune hemolytic anemia.
SET II.
Multiple-choice questions with 2, 3 or d) presence of previous disease;
more correct answers. e) predominant impairment of the
1. In which of the listed diseases does the imme- spleen, kidneys, liver, adrenals,
diate–type hypersensitivity reaction occur: intestine.
a) atopic bronchial asthma; 4. Which of the listed signs characterize the
b) anaphylactic shock; humoral immunodeficiency syndrome:
c) tuberculin-type reaction; a) thymic hypoplasia;
d) contact dermatitis; b) absence of immunoglobulins in
e) hemolytic disease of the new- the blood;
born. c) absence of germinal centers in
2. What macroscopic changes of the organs are lymph nodes;
observed in amyloidosis: d) the number of plasma cells is
a) reduced size; normal;
b) increased size; e) high frequency of severe infecti-

c) dense consistency; ons and septicemia.
d) flaccid consistency; 5. Which of the listed malignant tumors are
e) wax or bacon appearance. observed in AIDS more frequently:
3. Which of the listed signs are typical for AA a) skin cancer;
amyloidosis? b) Kaposi`s sarcoma;
a) the absence of previous disease; c) nephroblastoma;
b) generalized character of lesions; d) non-Hodgkin lymphoma;
c) predominant damage of the bra- e) multiple myeloma.
in, pancreas, arteries;
SET III.
The classification tests include 2–4 sub- II – of cellular type;
jects and a series of answers. Indicate which a) the antigen is destroyed by
answers are correct for each separate sub- immune cytolysis mechanism;
ject. b) B lymphocyte participation;
1. Which of the listed signs characterize the c) T lymphocyte participation;
immune reactions: d) the antigen is destroyed by immu-
I – of humoral type; ne phagocytosis mechanism;

e) the plasmocyte is the effector b) rheumatoid arthritis;
cell; c) Hashimoto thyroiditis;
f ) T–killer lymphocytes and ma- d) autoimmune orchitis;
crophages are the effector cells. e) scleroderma.
2. What are the areas of distribution of: 4. Which of the listed diseases are characteri-
I – B lymphocytes; zed by the following auto antibodies:
II – T lymphocytes; I – antinuclear;
a) the cortical layer of the lymph II – against IgG;
nodes; III – antinucleolar;
b) the paracortical layer of the IV – anti–basement membrane;
lymph nodes; a) glomerulonephritis;
c) the medullar layer of the lymph b) systemic lupus erythematosus;
nodes; c) systemic sclerosis;
d) the centrofollicular (periarterial) d) rheumatoid arthritis.
area of lienal lymph follicles; 5. In which of the listed diseases may develop:
e) the peripheral area of lienal I – AL amyloidosis;
lymph follicles. II – AA amyloidosis;
3. Which of the listed diseases are parts of: a) syphilis;
I – organ-specific autoimmune diseases; b) plasmacytic dyscrasia;
II – systemic autoimmune diseases; c) Crohn disease;
a) disseminated lupus erythemato- d) Hodgkin lymphoma;
sus; e) chronic osteomyelitis.
Daily practice cases are presented with a) local anaphylactic reaction (type I);

clinical and morphological data from clini- b) systemic anaphylactic reaction
cal histories and/or from necropsy protocols. (type I);
Each subject includes simple or multiple - c) cytotoxic hypersensitivity (type II);
answer questions, with 1, 2 or more correct d) reaction with toxic immune com-
answers. plexes (type III);
e) T-cell–mediated hypersensitivity
1. After eating certain foods, a 30-year-old
patient develops rash, redness and edema (type IV).
of the skin. 2. A man, who was bitten by a stray dog was
prescribed a course of antirabic vaccination.
Questions: A fever up to 38° appeared in 30 minutes
A) What is the correct name of this patho- after the IV injection, as well as redness and
logical process: swelling in the vaccine site.
a) hyperkeratosis; Questions:
b) dermatitis;
c) erysipelas; A) Which hypersensitivity reaction, from
d) hives; those listed, is involved in this case:
e) ichthyosis. a) atopic;
B) Which of the listed hypersensitivity b) idiosyncratic;
c) Arthus phenomenon type;
mechanism are involved in this case?

d) serum disease type reaction; cles have an ordinary structure. The blood
e) contact dermatitis. analyses from the medical chart show a
B) Which is, in the majority of cases, the lack of T-lymphocytes and the number of
organ that is impaired and that can cause B lymphocytes is unchanged.
death: Questions:
a) brain;
A) What is the correct definition for
b) kidneys;
c) heart; thymic modifications:
d) ovaries; a) thymic aplasia;
b) thymic agenesis;
e) lungs.
c) thymic dysplasia;
3. After a wasp’s bite, a patient developed d) thymic hypoplasia;
Quincke allergic edema, localized in the e) thymic hyperplasia.
lax subcutaneous tissues of the face, buccal
B) What immunodeficiency syndrome de-
mucosa and upper respiratory tract.
velops in this case:
Questions: a) agammaglobulinemia;
A) Which complication is the most life b) severe combined immunodefici-
ency syndrome;
threatening for a patient:
c) IgA selective deficiency;
a) spastic abdomen pains;
d) DiGeorge syndrome;
b) larynx edema;
c) mucus hypersecretion; e) secondary immunodeficiency.
d) eyelids edema; 5. A 45- year-old patient has been suffering
e) bronchi spasm. from chronic pulmonary fibrocavitary tu-
B) Which pathogenic mechanism is in- berculosis for several years. Some weeks
volved in edema occurrence: ago, signs of nephrotic syndrome with pro-
a) T-lymphocyte action on the teinuria and edema appeared.
smooth muscular cells; Questions:

b) IgA from the surface of baso-
A. What renal complication developed in
phils and mastocytes;
c) IgA from the surface of lympho- this patient:
cytes and eosinophils; a) glomerulonephritis;
d) IgE from the surface of baso- b) pyelonephritis;
phils and mastocytes; c) renal calculosis;
e) IgE from the surface of lympho- d) reactive amyloidosis;
cytes and eosinophils. e) renal carcinoma.
B. Which of the listed staining should be
4. A 1,5-year-old child died from acute pneu-
applied in renal biopsy to establish dia-
monia. The necropsy and the histopatholo-
gical examination of the corpse assays re- gnosis:
vealed: incomplete development of thymus, a) Sudan III;
its small dimensions, unclear structure; the b) carmine;
paracortical layer lacks in lymph nodes; c) Congo red;
lienal and lymph nodes lymphatic folli- d) PAS reaction;
e) T or S thioflavin.

ADAPTIVE–COMPENSATORY PROCESSES Chapte r 7
ADAPTIVE–COMPENSATORY PROCESSES
The elements of adaptation of cel- perplasia); organization (encapsula-

lular (tissular) structures to certain new tion); 4) tissue morphological restruc-
conditions, modified by functional ac- turation; 5) metaplasia; 6) dysplasia.
tivity, prevail in the adaptive processes. Compensatory processes develop
It is a manifestation of the organism’s due to organ (tissue) alteration, under
interrelation with the external environ- the action of harmful factors. It is ori-
ment and can reflect different functional ented towards correction of functional
conditions, for example, functional over- disturbances, which appeared during
strain, hypofunction or denaturation of diseases. This group includes: a) regen-
the tissue (organ) function. The main eration; b) compensatory hypertrophy
adaptive processes are the following: 1) (hyperplasia).
atrophy; 2) adaptive hypertrophy (hy-

7 . 1 . A D A P T I V E P RO C E S S E S
7.1.1. ATROPHY
Atrophy is reduction in size of cells, ferent causal factors. The following ca-
tissues, organs, with a decrease of their chexia variants are distinguished:
functional activity. It can be physiologic 1) alimentary cachexia – caused by
and pathologic, general and local. subnutrition or disturbed assimi-
Physiologic atrophy is observed in lation;
different age groups, for example, atro- 2) cancerous cachexia – is observed
phy of umbilical vessels in the newborn, in malignant tumors, as a result of
of arterial canal (Botallo duct) in the nutritional disorders, enzymatic
first three months of extra uterine life, system and digestive gland secre-
atrophy of sexual glands, skin, bones and tion disturbances, cancerous in-
other tissues (organs) in old people. toxication;
Pathologic atrophy can has a gener- 3) endocrine cachexia – appears as a
al or local character. consequence of endocrine glands
General pathologic atrophy or function disturbance (pituitary,
cachexia (Greek kakos – bad and hexis thyroid gland);
- condition) can be conditioned by dif- 4) cerebral cachexia – caused by in-

Chapter 7 ADAPTIVE–COMPENSATORY PROCESSES
flammatory or tumor processes in 3) ischemic (vascular) atrophy is

the hypothalamus area; caused by decreased arterial blood
5) cachexia in some chronic infec- supply, for example, in atheroscle-
tious diseases, e.g. in tuberculosis,
chronic dysentery, AIDS.
One observes the disappearance of
the subcutaneous adipose tissue in gen-
eral atrophy, as well as size and mass
decrease of all organs and tissues, with
decrease of their function. In organs,
especially in the myocardium and liver,
the lipofuscin pigment accumulates and
stains them with brown color (brown at-
rophy) (Fig.7–1). Fig. 7–2. Neurogenic atrophy of striated muscle
rosis of cerebral arteries (brain

atrophy, Fig. 7–3), renal arteries
(kidney atrophy);
4) compression atrophy – as a con-
sequence of mechanical compres-
sion of the functional organ paren-
Fig. 7–1. Brown atrophy of the liver.

Local pathological atrophy may be

caused by various etiologic factors. The
following varieties of local atrophy are
distinguished:
1) dysfunctional atrophy is caused
by inactivity, decrease or suspen-
sion of functional activity of the
organ, for example, muscle atro- Fig. 7–3. Bilateral ischemic atrophy of the brain
(on the left – normal brain).
phy in bone fractures, gallbladder
atrophy in the cystic duct obstruc- chyma, leading to its ischemia, for
tion by gallstones, atrophy of the example, in benign or malignant
teeth ridge after tooth removal; tumors, fluid accumulations (in
2) neurotic atrophy – it appears after hydronephrosis – dilatation of renal
trophic innervation disturbance, pelvis and calyces by aseptic urine
for example, in traumas with mo- accumulation, hydrocephalus – ac-
tor nerve injury, nervous tumors, cumulation of cerebrospinal fluid
poliomyelitis; it is more demon- in the cranial cavity (Fig.7–4));
strative in the skeletal muscles 5) atrophy caused by physical and
(Fig.7–2);

chemical factors, for example, in- and atrophy of hematopoietic tis-
hibition of regenerative processes sues and sexual glands, due to the
penetrating radiation, atrophy of
endocrine glands after a long use
of hormonal drugs.
Atrophy consequences depend on
the degree of organ’s reduction and the
decrease of its function. Pathological
atrophy is a reversible process. After
removing the cause of the atrophy, it is
possible to restore the structure and the
function of the affected organ complete-
ly, for example, restore muscles after
Fig. 7–4. Compression atrophy of the cerebral bone fracture healing.
tissue in internal hydrocephalus.
7.1.2. ADAPTIVE HYPERTROPHY (HYPERPLASIA)
Hypertrophy is the increase in size ²² acromegaly – hypertrophy and dis-

and mass of cells, tissues, organs, and proportionate growth of arms, legs,
hyperplasia is the increase of the num- jaw, ears, nose; it is caused by hyper-
ber of the structural elements of tissue secretion of the somatotropic hor-
and cells. Hypertrophy of an organ (tis- mone in the eosinophilic adenoma
sue) can be produced by multiplication of the pituitary gland; gigantism
of cells, by increasing the number and develops in children and adoles-
size of intracellular elements or by com- cents;

bination of both these processes. There ²² glandular endometrial hyperplasia,
are two varieties of hypertrophy/hyper- resulting from hypersecretion of es-
plasia of adaptive nature: 1) neurohor- trogen hormones (Fig. 7–5);
monal hypertrophy and 2) hypertrophic ²² gynecomastia – hypertrophy of the
proliferations.
Neurohormonal (neurohumoral)
hypertrophy is an adaptive process (not
compensatory) that occurs as a result
of neurohormonal disorders with alter-
ation of hormone balance, which exer-
cises a stimulating action on the growth
of organs and tissues. Examples:
²² hypertrophy of uterus and mam-
mary glands during pregnancy and
lactation, under the action of ovari-
an corpus luteum and placental hor- Fig. 7–5. Glandular hyperplasia of endome-
trium (hematoxylin–eosin stain; ×70).
mones;

mammary glands in males, caused ²² development of elephantiasis in

by testicular hypofunction (testos- chronic lymphostasis;
terone hyposecretion); ²² adipose and connective tissue pro-
²² nodular hyperplasia of the prostate liferation in cases of partial or total
in elderly men, caused by androgen organ atrophy (pseudohypertrophy
hormones hyposecretion and an- or false hypertrophy), for example,
drogen/estrogen balance shift. in atrophy of kidneys, skeletal mus-
Hypertrophic proliferations lead to cles;
size increase of tissues and organs and ²² blood vessel intimae proliferation in
have a diverse origin. Examples: blood pressure decrease.
²² development of hyperplastic pol-
yps on the mucous membranes in
chronic inflammation;
7.1.3. ORGANIZATION AND ENCAPSULATION
The organization is the substitution granulation tissue occur during the pro-
with connective tissue of some necrosis cess of organization.
foci, exudates (Fig.7–6), thrombi, hema- Encapsulation is the delimitation of
tomas, tissular defects, parasites, foreign necrotic focus, infarction, foreign body,
bodies. The removal of necrotic masses, parasite, etc. by a fibrous connective tis-
fibrin, exudates, products of tissue dis- sue membrane (Fig. 7–7).
integration and their replacement by
Fig. 7–6. Organization of pulmonary alveoli Fig. 7–7. Encapsulation of caseous necrotic
exudate in unresolved pneumonia (pneumo- focus in tuberculosis (hematoxylin–eosin sta-
nia in course of organization or carnification) in; ×70).

7.1.4. MORPHOLOGICAL RESTRUCTURATION OF TISSUES
It is an adaptation reaction of tissues tical to the structure of large vessels);

to new functioning conditions, being ²² transformation of flat alveolar epi-
also called histological accommoda- thelium in cubic epithelium in atel-
tion. Examples: ectases;
²² dilatation and hypertrophy of col- ²² transformation of the nephrothe-
lateral blood vessel walls, in case of lium of the renal glomerular cap-
blood circulation disorder occurring sule in cubic epithelium, in case of
in the magistral vessels (hypertrophy glomerulus sclerosis and hyalinosis;
of smooth muscle cells and neofor- ²² thickening of cranial bones in case
mation of elastic fibers occur, the of brain atrophy (also called ex vac-
small vessel structure becomes iden- uo hypertrophy).
7.1.5. METAPLASIA
Metaplasia is transformation of a dif- of the epithelium of excretory ducts,
ferentiated adult tissue into another type salivary glands, pancreas, biliary tract,
of adult tissue, differentiated as well. It is which is observed more frequently in
a process of tissue adaptation to modified calculosis. In all these cases, the denser
functioning conditions. The transforma- and more compact stratified squamous
tion of a tissue into another occurs only epithelium is more resistant to the ac-
within one and the same germ layer, by tion of harmful factors, which can alter
proliferation of young cells. It is observed the specialized and more fragile colum-
more frequently in the coating epitheli- nar epithelium. It should be noted that
um and connective tissues. Metaplasia is the stratified squamous epithelium is

a reversible process and it usually occurs not functional in these cases. One also
as a response to chronic irritation and in- observes intestinal metaplasia of gastric
flammation, avitaminosis A (vitamin A mucosa epithelium, gastric or intestinal
deficiency induces epithelial metaplasia type metaplasia of stratified squamous
and its excess stops the keratinization). epithelium lining the esophagus mucosa
The biological role of metaplasia is to (Barrett esophagus), squamous metapla-
replace more sensitive and vulnerable
cells with others, more resistant and able
to survive under certain unfavorable en- 1 2
vironmental conditions. The squamous
(epidermoid) metaplasia of the glandular
epithelium is observed most frequently,
when the respective epithelium is substi-
tuted with stratified squamous epitheli-
um with or without cornification.
Examples: squamous metaplasia of
trachea or bronchi epithelium in smok-
Fig. 7–8. Squamous metaplasia (2) of glandular
ers (Fig. 7–8), of uterus cervical canal
respiratory epithelium (1) (hematoxylin–eosin
epithelium in chronic endocervicitis, coloration; ×70).

sia of the transitocellular epithelium of For example, the squamous lung can-
urinary tract. The process of metapla- cer begins in the squamous metapla-
sia does not imply a direct transforma- sia foci of the bronchial epithelium.
tion of one epithelium into another: the Connective tissue metaplasia with ap-
transformation occurs by multiplication pearance of cartilaginous, bony or adi-
of cambial cells, which are not differen- pose tissue is observed in sclerosis foci,
tiated in the glandular epithelium, but in scars, adhesions, in the stroma of tumors,
the stratified squamous epithelium. in the capsule of healed foci of caseous
Metaplasia is not considered di- necrosis in tuberculosis etc. Metaplastic
rectly carcinogenic. It can induce ma- tissue formation starts with proliferation
lignant transformation of metaplas- of young connective tissue cells, which
tic epithelium, only in cases where the are subdivided in chondroblasts, osteo-
causative factor persists for a long time. blasts, lipoblasts.
7.1.6. DYSPLASIA
Dysplasia is a pathological process There are three stages of dysplasia:

manifested by marked disorders of epi- I – mild, II – moderate (Fig. 7 – 9) and
thelium proliferation and differentiation, III – severe. Sometimes, it is difficult to
with development of cellular atypism establish the boundary between them. If
and disturbance of its hystoarchitecton- nuclear immaturity is observed in all ep-
ics. Atypical hyperplasia is a synonym to ithelial layers, including the superficial
dysplasia. ones, the lesion is classified as severe.
Main characteristics: If nuclear immaturity is located only in
ØØ epithelial stratification is preserved, basal layers of epithelium, the injury is
but the orientation of cells within considered mild. It is often very difficult
the layers is changed; epitheliocyte or even impossible to make a clear dif-
polarity and sometimes of features ferentiation between III grade dysplasia

specific for the given tissue or organ and carcinoma “in situ”. The early I and
are lost; II stages of dysplasia are often reversible;
ØØ changes of cellular nuclei, their size the III stage is considered a precancer-
and hyperchromatism increase; ous condition.
ØØ variability of cell size and shape;
ØØ increase of mitotic activity, number
of mitoses and their appearance in
all epithelial layers;
ØØ intact, unaltered basement mem-
brane of epithelium.
The listed characteristics demon-
strate clearly that dysplasia is more a tis-
sular concept than a cellular one.
Dysplasia occurs in inflammatory
and regenerative processes, as a mani-
Fig. 7–9. Moderate dysplasia of ectocervical
festation of abnormal cell proliferation
epithelium: thickening of basal layer, hyper-
and differentiation. It is also observed in chromatosis of nuclei, mitotic figures (hemato-
epitheliums in metaplasia. xylin–eosin stain; ×70).

7 . 2 . C O M P E N S ATO RY P RO C E S S E S
7.2.1. REGENERATION
Regeneration is the process of re- ²² intracellular form – manifest-

covery (renewal) of the structural ele- ed by multiplication and size in-
ments of tissue (organ) instead of those crease of cytoplasmic organelles
destroyed. Both restoration of structure (nuclei, mitochondria, ribosomes,
and function of altered tissues (cells) oc- etc). This form of regeneration is
cur during regeneration. shown schematically in the Fig.
Regeneration can occur in two mor- 7–10: in case of partial necrosis of
phological forms: the cell (Fig.7–10 b), its function is
²² cellular form – multiplication of compensated by hyperplasia of cy-
cells, their mitotic (indirect) or toplasmic organelles from the pre-
amitotic (direct) division; served portions of the same cell.
a b

Fig. 7–10. Schematic presentation of the intracellular regeneration: a – normal cell; b – partial cell ne-
crosis and hyperplasia of the remaining cytoplasmic organelles with reestablishment of their number.
Two distinct stages are distinguished cells and of intracellular organelles. The
in the regenerative process evolution: 1) immature cells become mature in the sec-
proliferation and 2) differentiation. The ond stage and acquire some specific func-
first stage includes the multiplication of tional, structural features. The immature
young, immature, undifferentiated cells – intracellular organelles undergo the same
the so-called cambial, stem or precursor process of maturation and differentiation.
7.2.1.1. VARIETIES OF REGENERATION
There are three varieties of regener- processes at the molecular level, hence
ation: a) physiological; b) reparative; c) the vital need of constant intracellular
pathological. renewal. Physiological regeneration is
Physiological regeneration. It en- carried out continuously throughout
sures the normal function of all organs life and is characterized by continuous
and tissues, because each function is renewal of cells, fibrillar elements and
based on decomposition and synthesis ground substance of connective tissue. It

occurs at the subcellular level; the bio- nisms provide the ability to restore tissue
chemical (molecular) permanent regen- defects, both full restoration of previ-
eration, which is the structural equiva- ous tissue and incomplete restoration
lent of body functions, occurs. through scarring of the affected area.
Reparative regeneration is regen- Growth factors have an important role:
eration from different pathological to regulate the regeneration and repair
processes, when alteration of cells and processes. They originate from epithelial
tissues takes place. It manifests itself altered cells, platelets and macrophages.
through the same morphological mech- The main growth factors are:
anisms as the physiological regeneration, ²² epidermal growth factor, EGF (epi-
representing, in fact, physiological regen- dermal growth factor) that stimulates
eration in the sick body; it starts concom- the regeneration of specialized epi-
itantly with the action of the harmful thelial cells;
factor. Reparative regeneration may be ²² factor that activates the fibroblasts
complete (restitution) and incomplete – TGFβ (transforming growth factor
(substitution). beta);
Complete regeneration is charac- ²² angiogenetic factor, which stimu-
terized by the replacement of the defect lates the formation of new capil-
with a tissue identical to the destroyed laries – VEGF (vascular endothelial
(preexisting) one. It is observed in tis- growth factor).
sues where the cellular form of regener- The nature and intensity of the re-
ation prevails, for example, in connective generation process depend on many lo-
tissue, bones, skin, digestive, respiratory cal and general factors, for example:
and urogenital tract mucosa, vessel en- ²² age (regeneration intensity in the
dothelium, serous membrane mesotheli- elderly is much lower compared to
um, hematopoietic tissue. the childhood period);
Incomplete reparative regeneration ²² nutritional status (regeneration is

is characterized by replacement of de- much slower in obese and cachectic
fect with cicatricial connective tissue, people);
and functional parenchyma restoration ²² metabolic condition, such as protein
occurs through hypertrophy of the re- deficiency and avitaminoses, which
maining part of the organ, known as influence negatively the regenera-
regenerative hypertrophy. The latter can tion processes;
be done in two ways: 1) cell hyperpla- ²² blood and lymph circulation con-
sia (observed in liver, kidney, pancreas, dition (ischemia, venous and lym-
lungs, etc.); 2) hyperplasia and hyper- phatic stasis endanger the regener-
trophy of intracellular organelles, i.e. cell ation process);
hypertrophy (observed in myocardium ²² hematopoiesis condition (the inten-
and brain). sity of regeneration decreases con-
The regeneration of altered tissues siderably in anemia, leukopenia and
takes place in accordance with the same lymphopenia);
mechanisms that regulate tissue growth ²² innervation condition (regenera-
and differentiation during normal con- tion is disturbed in denervated ar-
ditions of development. These mecha- eas or in patients with paralysis);

²² particularities of the pathological bone thickening and deformation
process, firstly, type and size of tissu- in fractures (Fig. 7–16), amputation
lar injury, for instance, burn wounds neuroma (Fig. 7–22);
are healing more difficult; ²² hyporegeneration – insufficient
²² regenerative potential of tissue/or- formation of regenerative tissue, e.g.
gan. deficient bone callus in fractures
The Pathological regeneration is with occurrence of pathological mo-
the abnormal, atypical regeneration, bility of bone fragments or pseudo-
characterized by quantitative or qualita- arthrosis, in trophic skin ulcers (Fig.
tive changes of the regenerative process. 7–29);
It is caused by innervation and circula- ²² metaplasic regeneration – appear-
tory disorders, protein and vitamin defi- ance in the regenerative process of
ciency, chronic inflammation. a different tissue compared to the
It may manifest itself through: previous one, for example, stratified
²² hyperregeneration – exaggerated squamous epithelium foci in the
neoformation of regenerative tissue, bronchi, trachea mucosae (Fig. 7-8),
for example, excess of granulations cervical canal, endometrium, etc.,
(exuberant granulations) or cicatri- which, under normal physiological
cial connective tissue (keloid scars) conditions, are covered with glan-
after healing of wounds, burns (Fig. dular epithelium (squamous meta-
7–30), exostoses (bony growths), plasia).
7.2.1.2. REGENERATION OF VARIOUS TISSUES AND ORGANS
According to the regeneration po- generate intensely, both by cellular and

tential, the cells can be divided into intracellular ways, providing structural
three categories: and functional restoration of the altered
Labile cells, which multiply organ. This group includes liver, kidneys,
throughout life, with a continuous turn- lungs, exocrine parenchyma of pancreas,
over, both in physiological and patho- skeletal and smooth muscles, endocrine
logical conditions. Such features are system, including pancreatic insular ap-
observed in skin epithelial cells (epider- paratus, glial cells. In these organs, the
mis), mucous membranes of gastrointes- epithelium regeneration can be made
tinal, respiratory and urogenital tracts, both by cell hyperplasia and association
hematopoietic system cells, endotheli- of cell hyperplasia with their hypertro-
um, mesothelium, bone, lax connective phy, which is produced by hyperplasia of
tissue cells. The regenerative potential is subcellular (cytoplasmatic) elements.
very high and injury cure is complete in Permanent cells that do not possess
most cases. proliferation capacity in the postnatal
Stable cells, with a low intensity of period and regenerate only intracellu-
physiological regeneration, but a high larly. The regenerative and hyperplastic
potential of reparative regeneration. In intracellular processes provide the ma-
pathological conditions, when tissue terial substrate for the compensation
lesion occurs, the remaining cells re- of the altered functions during patho-

logical processes. This phenomenon is lar regeneration. Granulation tissue

observed in cardiomyocytes and nerve formation starts with proliferation
cells, where the regenerative hypertro- (division) of young mesenchymal
phy is conducted exclusively by hyper- cells and neoformation of blood
trophy of remaining cells, which, in its microvessels. Macroscopically, it is
turn, is produced by hyperplasia and/or a soft, juicy tissue, of a reddish col-
hypertrophy of intracellular structures. or, with granular surface (hence the
The structural–functional peculiari- name), the granules being composed
ties of the altered tissue/organ and the from new formed vessels. It bleeds
expansion of the lesion have an import- easily because of the large number
ant role in regenerative processes. of capillaries (Fig. 7–11). Micro-
²² Connective tissue regeneration. It scopically, numerous blood vessels
occurs in two stages: 1) granulation are observed, including capillaries,
tissue and 2) mature connective tis- among which there are many young
sue. cells (polymorphonuclear leuko-
Granulation tissue is the initial stage of cytes, macrophages, lymphocytes,
the connective tissue regeneration, plasma cells, fibroblasts). There are
being, actually, a young connective small caliber vessels, with thin walls
tissue, rich in cells and blood vessels (Fig. 7–12). In dynamics, with the
and poor in collagen fibers. It is a attenuation of the inflammato-
typical example of complete, cellu- ry process, the number of cells and
Fig. 7–11. Granulation tissue – macroscopic as- Fig. 7–12. Granulation tissue (hematoxylin–eo-
pect. sin stain; ×70).
Fig. 7–13. Granulation tissue during maturati- Fig. 7–14. Fibrous cicatricial connective tissue
on (hematoxylin–eosin stain; ×70). (hematoxylin–eosin stain; ×70).

blood vessels is reduced gradual- Complete restoration just of the in-
ly; mesenchymal cells (stem cells of ternal tunic – of endothelium – occurs
connective tissue) are transformed in the regeneration of large blood and
into epithelioid cells and latter - in lymphatic vessels, and the middle and
fibroblasts. Fibroblasts prevail in the external tunic defects are replaced by
granulation tissue under maturation fibrous connective tissue, which can re-
and the number of vessels reduces sult in deformity and narrowing of the
progressively (Fig.7–13). The in- vascular lumen.
crease of fibroblast activity and the ²² Bone tissue regeneration in bone
intense production of collagen fibers fractures. The evolution of fracture
occur simultaneously, vessels turn healing process depends largely on
into arteries and veins. The process the degree of destruction of bone
of granulation tissue maturation ends tissue, nature of fracture (with or
with a fibrous (cicatricial) connec- without splinters), movement of the
tive tissue formation, where a small broken bone ends under the action
number of fibrocytes and vessels is of adjacent muscles, correctness of
met (Fig. 7–14). The neoformation bone fragment reposition, age and
of granulation tissue occurs not only general condition of the patient,
in connective tissue regeneration, but local conditions (state of blood cir-
also in cases of incomplete regenera- culation, inflammation, presence of
tion of other organs (when the defect infection etc.).
is replaced by connective tissue), and Regeneration undergoes the follow-
in organization processes, encapsula- ing stages in uncomplicated (closed, un-
tion, wound healing and productive infected, without displacement of frag-
inflammation. ments) fractures:
²² Regeneration of blood and lymphat- I) formation of a hematoma between

ic vessels differs according to their fractured bone ends;
caliber. II) hematoma organization and fibrous
Microvessel regeneration can occur callus formation;
in two ways: III) fibrous callus ossification by the
a) budding of existing capillaries, temporary bony callus formation
when lateral protrusions appear in through proliferation of osteo-
their wall, due to the intense pro- blasts in the periosteum and end-
liferation of endothelial cells with osteum; poorly calcified bone tra-
formation of cellular cords, where beculas appear in the new formed
lumens appear later, continuing the tissue; bone regeneration is impos-
original capillary; sible without the presence of peri-
b) autogenous neoformation of capil- osteum;
laries, when clusters of undifferenti- IV) formation of definitive bone cal-
ated cells that transform into endo- lus through maturation of tem-
thelial cells appear in the connective porary bone callus; it turns into a
tissue; subsequently, fissures appear mature, dense, less vascularized and
in these clusters and merge with less bulky bone, which differs from
preexisting capillaries. normal bone tissue only by the cha-

otic disposition of bone trabeculas crescences, exostoses, bone deformity in

(Fig. 7–15); the fracture site (Fig. 7–16).
V) functional reconstruction, remod- Regeneration of muscle tissue. It oc-
eling of neoformed tissue with bone curs differently, depending on the type
trabecula restructuring, according to of tissue.
Fig. 7–15. Bone callus on the fracture site. Fig. 7–16. Vicious bone callus in femoral frac-
ture.
the functional requirements of the The small defects in smooth muscles

respective bone. As a result, the frac- are restored completely by multiplication
ture area returns to normal and the of adjacent leiomyocytes or by metapla-
bone fracture site can be observed sia of connective tissue cellular elements.
neither clinically nor radiologically, The large defects of the smooth muscle,
over a period of time. e.g. in the gastric or intestinal walls, are

In case of unfavorable local condi- replaced by fibrous scars and persistent
tions, for example, in rib fractures, when muscle fibers are subjected to regenera-
immobilization is practically impossible, tive hypertrophy.
a cartilaginous tissue appears initial- Complete regeneration occurs in
ly between the broken bone fragments, skeletal striated muscles only in cases,
a preliminary osteocartilaginous callus, when myocyte sarcolemma is preserved.
which subsequently turns into mature Multiplication of cambial or satellite
bone tissue. This way of fracture healing cells, located in sarcolemma thickness,
is frequently met and lasts longer. between the basement membrane and
The correcteness of reposition and plasmalemma, occurs inside the muscle
immobilization of bone ends, infection tube. In symplast destruction, after re-
penetration, blood supply condition and moval of muscle debris by macrophages,
nutrition in general (proteins, calcium, intense activation and division of satel-
vitamins D and C), age have a key role lite cells (myoblasts) take place, which
in the healing process of bone fractures. fill the delimited sarcolemma sheath,
The disorders of bone fracture heal- forming chains. Later on, their myo-
ing process manifest themselves by ap- genic differentiation, contractile protein
pearance of pseudoarthroses, bone ex- synthesis, myofiber assembly, sarcomeres

formation and muscle fiber restoration Regeneration of specialized epithe-
occur. In cases when sarcolemma is in- lium of parenchymatous organs (liver,
jured, the defect is replaced by connec- kidneys, pancreas, lung alveoli and en-
tive tissue scar (muscle callus); some docrine glands) is produced by injured
protrusions (expansions) with many nu- tissue cicatrization and regenerative hy-
clei appear at the broken ends of inter- pertrophy of the remaining parenchy-
rupted muscle fibers, called muscle buds ma. It is very important, if the support
and the muscle fiber continuity is not tissue (stroma) is preserved. Epithelial
restored. Myofibrils disappear in these cells proliferate and move along the
buds, cytoplasm becomes basophilic, reticulin network during regeneration.
they can detach from the original fiber Concomitant damage to parenchyma
and transform into giant multinucleated and fibrous connective tissue stroma
cells of myogenic origin (Fig.7–17). leads to organization and scarring of
altered areas.
The liver has a remarkable regen-
erative capacity. The organ’s weight is
restored, even after a resection of 2/3,
already in two weeks. Complete regen-
eration (restitution) of the liver occurs
in cases of small necroses and after re-
section. The remaining portions of the
organ undergo hypertrophy by cellular
hypertrophy and hyperplasia with sub-
Fig. 7–17. Regeneration of striated muscle (he- sequent remodeling in the liver lobules
matoxylin–eosin stain; ×70). with normal histological structure. The
massive necroses and injuries caused

²² Epithelial regeneration. The epi- by long-term action of harmful fac-
thelial regenerative potential is very tors lead to incomplete regeneration
high, especially of skin epithelia. (substitution) of the liver. Hyperplasia
Usually, large defects of the skin re- and hypertrophy of hepatocytes are ob-
generate completely. Initially, an in- served in the persistent hepatic paren-
tense multiplication of the germinal chyma. Regenerative nodules, penetrat-
layer cells occurs at the edges of the ed by fibroconnective septa, appear and
defect, covering it in one layer, then, are called pseudo– lobules, because they
the neoformed epithelium becomes lack radial orientation of liver trabecu-
stratified, gains polarity and other las and the vessels are placed incorrectly
features of normal epithelium. Re- (central veins are missing or are located
storing the skin epithelium becomes eccentrically, triads are not always de-
possible only after filling the defect tected).
with granulation tissue. Also, the The regenerative process is mani-
mucosal epithelium regenerates ac- fested by appearance of bi– and poly-
tively through proliferation of cells, nucleic hepatocytes, increased number
which cover the crypts and excre- of mitoses and hyperchromic nuclei.
tion ducts of glands. Simultaneously, proliferation of biliary

epithelium takes place, with neoforma- ²² Myocardium regeneration.

tion of genuine biliary ducts (with lu- Neoformation of muscular cells does
men) or pseudo-ducts (without lumen) not take place in myocardium and the
(Fig. 7–18 a, b). regeneration is incomplete. The lesion
a b
Fig. 7–18 a, b. Regeneration of liver in cirrhosis: a – microscopic aspect (hematoxylin–eosin stain;
×70); b – macroscopic aspect.
focus (infarct area) is replaced by cic- lishment is realized through the hy-
atricial fibroconnective tissue (post- pertrophy of the remaining myocardial
infarction macrofocal cardiosclerosis, fibers, primarily those in the immedi-
Fig. 7–19 a, b), but structural reestab- ate vicinity with the postinfarction scar
I II
a b
Fig. 7–19 a, b. Postinfarction macrofocal cardiosclerosis: a – macroscopic aspect (circular postin-

farction scar in the left ventricle wall); b – microscopic aspect (I – hematoxylin–eosin stain and
II – picrofuchsin van Gieson; ×70).
(regenerative hypertrophy). The latter myocardial hypertrophy (intracellular

is made through hypertrophy and/or regeneration). The ovals with septa
hyperplasia of cytoplasmic ultrastruc- indicate conventionally the function-
tures (Fig. 7–20). The contractile ac- al ultrastructures (for example, mito-
tivity of the heart after infarction is chondria), and those colorless – the
provided through hypertrophy of the altered ultra structures (Fig. 7–21 I a).
remaining portions of the heart mus- Structure reestablishment of the al-
cle. The Fig. 7–21 shows schematical- tered elements or their neoformation
ly the mechanism of the regenerative is observed during the intracellular re-

I II
Fig. 7–20. Regenerative hypertrophy of myocardium: I – hyperplasia of mitochondria, II – hyper-

trophy of mitochondria (electron microscopy, ×16000)
parative regeneration (Fig. 7–21 I b). changed; they are not located in two
In case of compensatory intracellular cells, but only in one. This ensures
hyperplasia, when a cell is necrotized the appropriate number of functional
(Fig. 7–21 II a), the number of cyto- structures, no matter how many cells
plasm ultrastructural elements is in- are arranged (D. S. Sarkisov, 1990).
creased in the persistent cell (II b). The ²² Regeneration of nervous system.
function is restored because the num- Brain and spinal cord neurons do not di-
ber of functional elements remains un- vide, so the restoration of damaged cells
a b a b
I II
Fig. 7–21. Schematic representation of the intracellular regeneration of the myocardium: I a, b –

intracellular regeneration, II a, b – intracellular regeneration with compensatory hyperplasia of
cytoplasmic organelles and regenerative hypertrophy of the remaining cardiomyocyte.
is impossible. The normalization of the The neuroglia regenerates in a cel-

altered functions of the nervous system lular or a mixed cellular and intracellu-
after an injury is produced only through lar way. Small necrotic foci are replaced
hypertrophy of persistent brain cells; hy- with glial tissue (fibro–glial scar).
pertrophy and hyperplasia of cytoplasm If a peripheral nerve is dissected, re-
elements occur. generation takes place due to the prox-

imal segment, which remains in contact the nerve fibers are arranged chaoti-
with the cell, but the distal segment dies. cally. These proliferations composed of
Phagocytosis of axon and myelin occurs nerve fibers and fibrous tissue are called
in the peripheral blunt, as well as pro- “amputation neuromas” (more correctly
liferation of Schwann cells, which are pseudoneuromas) (Fig. 7–22). They are
placed along the nerve, forming a tube, met at the sectioned nerve ends in limb
where the regenerative axons of the cen- blunt after their amputation.
tral segment penetrate. Nerve fibers,
from which one or more enter the neu-
ral tube, appear at the peripheral end of
the viable axon. Later, one of these fi-
bers is myelinated and turns into a new
functional axon. When the regenerative
process is disturbed due to considerable
movement of sectioned nerve ends, tis-
sue interposition between the section
heads or proximal segment inflamma-
tion, intense proliferation of connective Fig. 7–22. Amputation neuroma (hematoxylin–
tissue occurs and a scar appears where eosin stain; ×70).
7.2.2. HYPERTROPHY AND HYPERPLASIA

Hypertrophy may occur by increase vicarius – substitute).

of the number of cells (cell hyperplasia) Work (compensatory) hyper-
or by increase of their volume (intracel- trophy occurs as a consequence of
lular hyperplasia), or by combination of excessive functional activity of the
both processes. organ. Functional overuse of an or-
There exists true hypertrophy, due gan may occur both in physiological
to increased volume of specialized struc- conditions (muscle and heart hyper-
tures of the organ, and false hypertro- trophy in athletes, workers perform-
phy (pseudohypertrophy), when the in- ing physical work) and in diseases.
crease in volume and mass of the organ Examples:
is caused by excessive proliferation of ØØ left ventricle hypertrophy in hy-
connective and fat tissue. pertension, valvular heart dis-
According to the appearance mech- ease, primarily in aortic stenosis.
anism, there are two varieties of true hy- Heart mass can reach 600–1000g
pertrophy: (normal weight is 260–280 g),
1) work (compensatory) hypertro- the left ventricle wall thick-
phy; ens considerably, its thickness
2) vicarious hypertrophy (from Lat. can reach 2,5–3,0 cm (nor-

mal thickness is 1,0–1,2 cm); ventricle are enlarged
of the trabeculae and papillary (Fig.7–23 a, b).
muscles of the left
a b
Fig. 7–23 a, b. Hypertrophy of the left ventricle: a – longitudinal section, b – transverse section.
ØØ Right ventricle hypertrophy is ob- Concentric hypertrophy of the heart

served in small circulation hyper- is observed in the compensation period,
tension in different chronic lung when its cavities are narrowed and the
diseases: emphysema, pneumoscle- heart muscle tonus is increased. Micro-
rosis, chronic tuberculosis, bron- scopically, cardiomyocytes are enlarged;
chiectasis, interstitial pulmonary the nucleus is also increased, irregular-
fibrosis etc. (hence the name of ly shaped, intensely colored, basophilic
cor pulmonale or pulmonary car- (Fig. 7–25). Electron optically, sarco-
diomyopathy), as well as in cardi- plasm mass increase is detected, as well
ac valvular lesions, for example, in as cardiomyocyte nuclei size increase,

stenosis or valvular insufficiency of hyperplasia and hypertrophy of cytoplas-
the pulmonary artery (Fig. 7–24). mic organelles. Simultaneously, prolifer-
Fig. 7–24. Hypertrophy of right ventricle. Fig. 7–25. Hypertrophy of myocardium (hema-
ation of fibrillar structures of the stroma, takes place in the decompensation pe-
intramyocardial vascular branches and riod, when the heart cavities are dilated,
intramural nervous system elements of heart consistency is flaccid, with opaque
the heart occur. Eccentric hypertrophy appearance as a result of dystrophic le-

sions; myocardium steatosis is observed

(“tiger heart”). Hypertrophy reaches
a level, when the hypertrophied heart
muscle cannot compensate the increased
functional demands anymore and heart
failure develops. Heart dilatation at the
compensatory stage is called active or
tonogenic and in decompensation –
passive or myogenic.
Other examples: urinary bladder
wall hypertrophy in nodular hyperpla-
sia of prostate (Fig. 7–26), hypertrophy
of intestinal wall in stenosing tumors,
stomach hypertrophy in pyloric stenosis
etc.
Vicarious hypertrophy is the hy-
pertrophy of one of the paired organs
(lungs, kidneys, adrenals) after failure of
the contralateral organ and increased ef-
fort of the remaining organ. Fig. 7–26. Hypertrophy of urinary bladder wall
in nodular hyperplasia of prostate.
7.3. WOUND HEALING

Wound healing evolves differently thelial defects. The epithelium extends

depending on the form, extent, depth of over the defect and closes it.
the wound, its character, absence or pres- Healing under the crust. It is ob-
ence of infection, foreign bodies, overall served in small defects of cornea and
condition of the body (age, nutritional mucous membranes. A crust formed of
status, immunity, circulatory, endocrine coagulated blood and lymph appears
and nervous systems etc.), local structur- on the surface of the defects; this crust
al features of the tissue (vascularization, protects the wound from the influence
innervation, regeneration capacity). of external environment factors and de-
The following variants of wound taches independently after epidermis
healing are distinguished: 1) immediate restoration (in 3–5 days after trauma).
closure of the defect, 2) healing under Healing per primam intentionem.
the crust, 3) wound healing by primary It is met in non-infected wounds, with
intention (primary union or per primam straight edges, the distance between
intentionem), 4) wound healing by sec- them does not exceed 1cm, usually in
ond intention (secondary union or per surgical incisions. Initially, a blood clot
secundam intentionem). forms between the edges of the wound,
Immediate closure of epithelial cover which contains fibrin and blood cells.
defect. It is observed in superficial epi- The fibrin clot binds the wound edges,

fills the space between them and there- of the wound is filled with granulation
by protects the wound from dehydration tissue. There is an intense neoformation
and possible infection. An inflammato- process of capillaries and collagen fibers,
ry reaction with sero–fibrinous exudate which, initially, are arranged vertically
and neutrophil leukocytes appears in and then horizontally, forming bridges
the wound edges, in the first 24 hours. that connect the edges of the wound.
Lysis of fibrin clot and tissue debris Epithelium proliferation continues: it
takes place, under the action of leuko- gradually thickens through stratification
cytic proteolytic enzymes. In 2–3 days, and differentiation, reaching a normal
leukocytes are replaced by macrophages, thickness of epidermis (Fig. 7–27). In
which continue the phagocytosis of cel- 10–15 days, the granulation tissue ma-
lular debris and fibrin. Simultaneous- tures completely, the wound defect is
ly, the basal cells of the neighborhood epithelialized definitely and the wound
epidermis proliferate, forming a con- heals to a fine scar. Skin annexes in the
tinuous, epithelial monolayer gradual- scar area are not restored (Fig. 7–28). In
ly. Proliferating keratinocytes elaborate surgical wounds, healing by primary in-
basement membrane components. By tention is accelerated by suture of wound
the 5th day, the space between the edges edges. Scar remodeling process lasts sev-

Fig. 7–27. Wound healing, proliferation of stra- Fig. 7–28. Skin wound healing, neoformed scar
tified squamous epithelium under the crust of tissue in subepidermal skin layer (no hair folli-
fibrin and necrotic masses (hematoxylin–eosin cles, sebaceous and sudoriferous glands) (he-
stain; ×70). matoxylin–eosin stain; ×70).
eral months, the scar tissue gradually ry and innervation disorders. The main
gains density and strength adequate to factor is the presence of infection, ac-
the functional requirements. companied usually by purulent inflam-
Healing per secundam intentionem mation, which promotes the expansion
occurs in large wounds (the distance of tissue necrosis in the wound edges,
between the edges is more than 1 cm), vessel thrombosis, circulatory disorders,
which are dehiscent, unsutured, irregu- exudate and granulation tissue abun-
larly shaped, infected, accompanied by dance. Wound healing by secondary in-
larger tissue damage, penetration of for- tention is distinguished by the following
eign bodies in the wound. It is favored characteristics:
by nutritional disorders, excess of corti- 1) extensive tissue defects, with large
costeroids, diabetes mellitus, circulato- amounts of necrotic debris and

fibrin, which produce an intense Finally, a formation of a large scar,

inflammatory reaction; with tissue retraction and deformation,
2) large amounts of granulation tis- occurs. Mutilating scars may form in the
sue (Fig. 7–11); case of large, irregularly-shaped wounds.
3) wound contraction, observed in Scar remodeling lasts several months,
large size wounds, due to the ap- e.g. in 3 months, the scar regains 80% of
pearance of myofibroblasts – al- the initial density and strength param-
tered fibroblasts, which contain eters.
elements of smooth muscle cells Wound healing disorders manifest
and have contractile features, fa- themselves through the appearance of
voring the retraction of wound atonic chronic ulcerations of the skin
surface and the reduction of its (Fig. 7–29), which may lead to develop-
size; ment of skin carcinoma, exuberant gran-
4) the process of wound healing ulations and keloid scars (Fig. 7–30).
by secondary intention is longer
compared with primary healing.
Fig. 7–29. Atonic (trophic) skin ulceration – Fig. 7–30. Keloid scar – macroscopic aspect.
macroscopic aspect.

ESSENTIAL TERMS
on the subject “ADAPTATIVE–COMPENSATORY PROCESSES”
glandular hyperplasia of
acromegaly pathological regeneration
endometrium
atrophy gynecomastia physiological regeneration
histological
bone callus pseudoarthrosis
accommodation
cachexia hyperplasia regeneration
compensatory
hyperregeneration regenerative hypertrophy
hypertrophy
compression atrophy hypertrophy reparative regeneration
dysfunctional atrophy hyporegeneration restitution
encapsulation ischemic atrophy substitution
exostosis keloid vicarious hypertrophy
wound healing per primam
ex vacuo hypertrophy local atrophy
intentionem
wound healing per secundam
false hypertrophy metaplasia
intentionem
general atrophy organization wound healing under crust
gigantism neurotic atrophy
TESTS

on the subject "ADAPTATIVE–COMPENSATORY PROCESSES"
SET I.
Multiple-choice questions with one cor- 2. Which of the listed statements characterize
rect answer. the pathological regeneration;
1. What is the correct definition of regenera- a) regeneration of injured tissues in
tive hypertrophy: various pathological processes;
a) substitution of pathologic focus b) substitution of the tissue de-
with connective tissue; fect with a tissue similar to the
b) complete restoration of previous destroyed one;
tissue; c) permanent renewal of the struc-
c) partial restoration of previous tural elements of the organ (tis-
tissue; sue);
d) disturbance of regenerative pro- d) quantitative or qualitative chan-
cess; ges in the regenerative process;
e) hypertrophy of the remaining e) substitution of defect with scar
portion of the organ (tissue). connective tissue.

3. What is the correct definition of hyper- b) leg atrophy in femoral artery athe-
trophy: rosclerosis;
a) substitution of a pathologic focus c) muscle atrophy after bone fracture;
with connective tissue; d) tissue atrophy in case of denervati-
b) increase of the number of structu- on;
ral elements; e) cachexia.
c) size and mass increase of cells, tis- 5. All the listed conditions promote wound
sue, organ; healing per primam intentionem, except
d) delimitation of the pathologic fo- for:
cus through the fibroconnective a) unsutured wounds;
capsule; b) sutured surgical wounds;
e) size and mass decrease of an organ c) wounds without bacterial infecti-
(tissue). on;
4. All the listed pathological processes are d) wounds with linear aspect of edges;
manifestations of local atrophy, with the e) small wounds up to l cm.
exception of:
a) bone wear in the tumor area;
SET II.
Multiple-choice questions with 2, 3 or and hypertrophy of intracellular organel-

more correct answers. les occur;
1. Which of listed morphological processes cha- a) bones;
racterize the reparative regeneration; b) pancreas;
a) the appearance of multi-laye- c) endometrium;
red squamous epithelium during d) nerve cells;
bronchial epithelium regeneration; e) myocardium.
b) regenerative hypertrophy of myo- 4. Which of the listed morphological processes

cardium; characterize the pathological regeneration?
c) false joint appearance after bone a) the appearance of gastric or intes-
fracture; tinal type epithelium in the eso-
d) renewal of epidermal cells; phageal mucosa;
e) restoration of liver parenchyma b) regenerative hypertrophy of nerve
after massive necrosis of liver, cells;
in intoxication with poisonous c) exostoses occurrence;
mushrooms. d) wound healing per primam inten-
2. In which of the listed organs does the re- tionem;
parative regeneration through cell hyper- e) keloid scar formation.
plasia occur: 5. Which of the listed signs are typical for the
a) myocardium; decompensation stage of the work hyper-
b) liver; trophy of myocardium:
c) skin; a) eccentric hypertrophy;
d) hematopoietic tissue; b) heart muscle flaccid consistency;
e) digestive tract epithelium. c) myocardial steatosis;
3. In which of the listed organs does the re- d) passive dilation of heart cavities;
parative regeneration through hyperplasia e) active dilation of heart cavities.

SET III.
The classification tests include 2–4 sub- urysm of the thoracic aorta;
jects and a series of answers. Indicate which c) muscle atrophy in cases of pa-
answers are correct for each separate subject. ralysis in patients with cerebral
1. Which of the listed morphological processes infarction;
characterize: d) muscle atrophy in ankylosis of
I – complete regeneration; joints in patients with rheuma-
II – incomplete regeneration; toid arthritis;
a) regenerative hypertrophy of e) maxillary bone atrophy after ex-
myocardium; traction of teeth;
b) regeneration of blood after he- f ) atrophy of the gallbladder wall
morrhage; in obstruction of the cystic duct
c) formation of postinfarction cica- with calculi.
trix in the spleen; 4. Which of the listed pathological processes
d) restoration of intestinal mucosa can cause:
in the site of superficial ulcer; I – kidney atrophy through compres-
e) restoration of the broken bone. sion;
II – ischemic atrophy of the kidney;
2. Which of the examples below characterize:
a) renal artery stenosis in athe-
I – reparative regeneration;
rosclerosis;
II – pathological regeneration;
b) ureteral stricture;
a) keloid scar formation;
c) basin calculi;
b) formation of a fine scar after sur-
d) nodular hyperplasia of prostate;
gical incision;
e) sclerosis and hyalinosis of renal
c) appearance of multi-layered arterioles in arterial hypertensi-
squamous epithelium in the cer- on.
vical canal mucosa;

d) complete healing of skin wounds; 5. Which of the listed wounds will heal:
e) restoration of liver mass after re- I – per primam intentionem;
section. II – per secundam intentionem;
a) a wound with dehiscence of
3. Which variant of atrophy do the pathologi- edges larger than 1 cm;
cal processes listed below refer to: b) a cut wound, with straight edges,
I – dysfunctional atrophy; without dehiscence;
II – compression atrophy; c) large burn-caused wound;
III – neurotic atrophy; d) overinfected wound;
a) atrophy of peritumoral tissues; e) surgical wound.
b) atrophy of sternum in the ane-

Daily practice cases are presented with 1. A 70–year–old patient, with diabetes
clinical and morphological data from clini- mellitus type II for more than 20 years,
cal histories and/or from necropsy protocols. came up with a cut wound on the right
Each subject includes simple or multiple - leg, which does not heal for a long time,
answer questions, with 1, 2 or more correct gradually turning into an ulcerous defect
answers. (atonic ulceration).

Questions: 3. A patient with frequent hemorrhages from

A) Which regeneration variant occurs in peptic gastric ulcer and signs of chronic
the given case: posthemorrhagic anemia died from acute
a) reparative; ischemic cerebral infarction. The necropsy
b) physiological; revealed that the bone marrow in the fe-
mur diaphysis is juicy, red (normally, in
c) pathological;
diaphysis, the bone marrow is yellow, con-
d) complete;
stituted from adipose tissue).
e) incomplete.
B) Which variant of this form of regene- Question:
ration occurs in the given patient? Which is the regeneration variant in this
a) metaplasia; case:
b) hyporegeneration; 1) work hypertrophy;
c) hyperregeneration; 2) compensatory hyperplasia;
d) dysplasia; 3) vicarious hypertrophy;
e) organization. 4) dyshormonal hypertrophy;
2. A patient had liver resection due to a lar- 5) neurogenic hypertrophy.
ge-size tumor, diagnosed histologically as 4. A patient died suddenly of acute myocardi-
benign tumor of vascular origin – caver- al infarction. The necropsy confirmed the
nous hemangioma. A year later, the lapa- diagnosis of myocardial infarction; conco-
roscopic examination showed that the sur- mitantly, it revealed that the right lung
face of the surgical wound was cicatrized had a considerably increased size and the
and the liver mass was restored through left lung was absent. He had had left pne-
hypertrophy of the remaining part of the umonectomy few years ago, due to a lung
organ. cyst.
Questions: Question:
A) Which regeneration variant occurs in What morphological changes occurred in

the given case: the right lung of this patient:
1) reparative; a) neurohormonal hypertrophy;
2) physiological; b) physiological hypertrophy;
3) pathological; c) interstitial pneumonitis;
4) complete; d) vicarious hypertrophy;
5) incomplete. e) diffuse pneumosclerosis.
B) Which morphological form of this re- 5. A patient, who had a myocardial infarc-
generation prevailed in this patient: tion, shows signs of cardiac insufficiency
1) hyperplasia of cytoplasmic or- during physical activities: cyanosis and
ganelles; edema in legs, dyspnea.
2) cell hyperplasia;
3) hypertrophy of remaining cells; Questions:
4) hypertrophy of cytoplasmic or- A) What morphological changes develo-
ganelles; ped in the site of the old myocardial in-
5) cellular anaplasia. farction in this patient:

a) intracellular regeneration; a) cardiomyocyte atrophy;
b) interstitial myocarditis; b) cardiomyocyte proliferation;
c) myocardial atrophy; c) proliferation of connective tis-
d) cardiomyocyte proliferation sue;
(neoformation); d) cardiomyocyte hypertrophy;
e) focal cardiosclerosis. e) blood vessel neoformation.
B) What morphological changes can be
detected in the periinfarct area of the
myocardium:

Chapter 8 TUMORS
TUMORS
Tumor (synonyms: neoplasm or blasto- ative stimulus. Other important feature

ma) – pathological process characterized of neoplasms is that the proliferative
by unlimited proliferation of cells. The process does not have a compensatory–
cell proliferation in tumors is uncon- adaptive character.
trolled, autonomous; it is not subject to Tumor pathology ranks on the 2nd
the regulatory systems of the body and place in the lethality structure from all the
continues after cessation of the caus- countries (after cardiovascular pathology).
8.1. ETIOLOGY AND PATHOGENESIS OF TUMORS

The factors that can cause tumor de- cers result from environmental factors.
velopment are called cancerogenic or car- The main theories, which tackle the
cinogenic factors. At present, it is established etiological and pathogenetic aspects of
that the transformation of a normal cell the tumorigenesis, are:
into a cancer cell is based on the occur- a) theory of chemical carcinogenesis;
rence of a mutation, under the mutagenic b) theory of physical (radiation) car-
action of some agents from the external cinogenesis;
environment. Epidemiological studies c) theory of viral (infectious) car-
have shown that 80–90% of human can- cinogenesis.
8.1.1. THEORY OF CHEMICAL CARCINOGENESIS
Numerous experimental studies on lead) and natural substances produced

animals have identified several chemi- by plants and fungi. Cases of profession-
cal substances with carcinogenic effect. al tumors (cancers) are also in favor of
The most important are: polycyclic ar- this theory.
omatic hydrocarbons, azo dyes (aniline), The following factors are important
aromatic amines and amides (naph- in chemical carcinogenesis: a) dosage
thylamine), some metals (cobalt, nickel, and duration of action of the chemical

TUMORS Chapte r 8
substance; b) way of entering the body; lung cancer.
c) physical–chemical nature of the re- 6) azo dyes, aniline (rubber industry)
spective substances; d) animal species, for example, causes urinary blad-
etc. der cancer.
The primary and most import- 7) aflatoxin Bl, produced by the As-
ant target of carcinogens is the nuclear pergillus flavus fungus, causes liver
DNA. cancer (through food contaminat-
Carcinogens induce proto-onco- ed by mould, for example peanuts).
gene mutations, transforming them into 8) nitrosamines and amides synthe-
active oncogenes, mutations in cancer– sized in the body from nitrates,
suppressor genes, mutations in genes which are in the food, contribute to
that regulate apoptosis. the development of gastric cancer.
Examples of chemical carcinogens: Other carcinogens:
4) alkylating agents, e.g. cyclophos- ²² asbestos – induces lung cancer,
phamide – immunosuppressant pleural mesothelioma;
in cancer treatment. Patients, who ²² arsenic - generates skin cancer;
are treated with this drug for a ²² hormones, for example, estrogens
long time, face an increased risk of have an important role in en-
other cancers. dometrial cancer, the reduction
5) aromatic hydrocarbons are con- of testosterone secretion has a
tained in cigarette smoke and have beneficial effect in patients with
a major role in the development of prostate cancer.
8.1.2. THEORY OF PHYSICAL CARCINOGENESIS

Radiant energy in the form of ul- among survivors of atomic explo-
traviolet rays or ionizing radiation can sions at Hiroshima and Nagasaki;
also cause cancer development. Solar ul- ²² high incidence of thyroid gland
traviolet radiation causes skin cancer or cancer in areas contaminated by
malignant melanoma localized particu- radiation from the Chernobyl nu-
larly on the open body parts, exposed to clear accident;
the sunstroke. The risk of these tumors ²² cancer cases in patients under-
is especially high in white population going treatment with radioactive
from geographic areas with long annual isotopes.
sunlight duration. The predisposition to The carcinogenic effect of radiant
skin cancer in patients, who suffer from energy depends on the way of action of
albinism, is well known. the radiation, dosage and duration of ex-
Also, the electromagnetic and cor- posure, for example:
puscular radiations have a carcinogenic ²² direct, repeated action of X–rays
effect, confirmed by many examples: on a certain body area predisposes
²² high incidence of lung cancer in to malignant tumors of the skin
miners working in radioactive ore and bones in that area;
mines; ²² inhaling gas or radioactive dust –
²² very high incidence of leukemia lung cancer;

Chapter 8 TUMORS
²² ingestion of radioactive iodine – mucosa epithelium and spermatogenic

thyroid cancer; epithelium, are particularly vulnerable.
²² radioactive metals, which pene- Mutations occur by direct action of radi-
trate the body and store in bones – ant energy or indirect effect of free rad-
tumors of bone marrow and bones. icals from water and oxygen. Corpuscu-
The carcinogenic effect of radiation lar radiation is much more carcinogenic
is related to its action on the cellular than electromagnetic radiation (e.g. X–
DNA and the emergence of mutations. or gamma rays).
The cells that proliferate extensively in
physiological conditions, primarily the
hematopoietic marrow, gastrointestinal
8.1.3. THEORY OF VIRAL CARCINOGENESIS
Experimental studies have shown a) Burkitt lymphoma, which occurs

that, in animals, many tumors have a vi- in children and adolescents in some
ral origin. Viruses have a less important countries in Equatorial Africa;
role in human cancer. However, there b) nasopharyngeal carcinoma, spread
exists a range of tumors, in which virus endemically in some regions of
participation is confirmed. China; Epstein-Barr virus ge-
Oncoviruses may contain DNA or nome is detected in cancer cells
RNA. in all cases;
The following DNA viruses are ob- c) B–cell lymphoma in patients with
served in the genesis of human tumors: immunosuppression, especially in

²² Human Papilloma Virus (HPV). AIDS;
The role of this virus in the eti- d) some forms of Hodgkin lymphoma.
ology of cancer is confirmed by ²² Hepatitis B and C viruses are as-
many examples: sociated with liver carcinoma.
a) the cells contain HPV type 16 or The risk of hepatic carcinoma is
18 in more than 90% of cervical very high in some geographical
cancer ; regions (China, South Africa),
b) genital warts (condyloma acumi- where viral hepatitis B and C are
nata) are caused by HPV types 6 endemic. The carcinogenic po-
and 11; tential of hepatitis virus is deter-
c) molecular research of cervical mined by its ability to cause cell
carcinoma associated with HPV necrosis, chronic inflammation
showed viral genome integration and regenerative hyperplasia of
into host cell’s DNA. hepatocytes.
²² Epstein–Barr virus belongs to the Among RNA viruses, the most
herpes–virus group. It is associat- prominent example is the human T-cell
ed with: lymphotropic virus type 1 (HTLV–1),

TUMORS Chapte r 8
associated with leukemia/lymphoma tween stimulating factors and cell di-
from T-lymphocytes with a strict tro- vision inhibitors is disturbed and this
pism for T-CD4 lymphocytes. This induces intensification of proliferative
form of leukemia/lymphoma is an en- processes. Proto-oncogene activation,
demic pathology in Japan, etc. inhibition of tumor–suppressor genes
The mechanism of action of blas- and apoptosis occur simultaneously in
tomogenic viruses is complex. For ex- many malignant tumors.
ample, the DNA virus enters the cell, The immune system status has a
is incorporated directly into the cell significant importance in tumor occur-
nucleus, but the RNA virus produces rence. Some types of cancers are ob-
a new DNA by means of the reverse served more frequently in patients with
transcriptase, which also is incorporat- immunosuppression, e.g. the patients,
ed into the host cell nucleus, activating receiving immunosuppressants for kid-
cellular proto–oncogenes. Thus, normal ney transplantation face a high risk of
cells are transformed into tumor cells. squamous skin cancer.
In cancer cells, the balance be-
8.1.4. PROTO–ONCOGENES AND CELLULAR ONCOGENES
At the molecular level, the carcino- depending on cellular or viral origin

genesis process is determined by non- (c–src, v-src). Oncogenes encode the
lethal lesions of the genetic material synthesis of proteins=oncoproteins,
of the cell, which manifest themselves which, according to their functional
through mutations of genes or cellu- characteristics, are subdivided into: a)

lar genome. The targets of mutagenic homologous oncoproteins of growth
factors are: a) proto-oncogenes, b) can- factors (c–sis), b) homologous oncopro-
cer–suppressor genes and c) genes that teins of growth factor receptors (c–erbA,
regulate apoptosis. c–erbB), c) oncoproteins involved in the
Cellular proto–oncogenes are genes functioning of receptors through pro-
present in the genome of every nor- tein kinases and G protein (c–src, c–abl,
mal cell. They regulate and stimulate c–ras) and d) oncoproteins – nuclear
cell division and differentiation, being, transcription factors (c–fos, c–myc).
usually, non–active in mature tissues. Activation of proto–oncogenes oc-
Initially, they were discovered in virus- curs through different mechanisms:
es (viral oncogenes) and, later, homolo- a) point mutations; b) translocation
gous human genes were identified. The of chromosome fragments contain-
active forms of the proto–oncogenes ing proto-oncogenes; c) amplification
are called cellular oncogenes. They have of proto-oncogenes (increase of the
the ability to induce tumor growth. The number of copies); d) insertion of viral
name of cellular oncogenes is formed genes into the cell genome, which can
from 3–letter abbreviations, such as src be oncogenes or can act as an activator
(from sarcoma), plus prefix c – or v –, (enhancer) of proto–oncogenes.

Chapter 8 TUMORS
Examples: 1) c–ras proto–oncogene in ocular retinoblastoma in children,

mutation occurs in urinary bladder which may be sporadic or hereditary.
cancer, c– rasK proto–oncogene mu- Besides the p53 gene, cellular on-
tation occurs in colon cancer; 2) mu- cogenes from c–bcl2 and c–myc families
tual translocation of c–myc gene from are regulatory factors of apoptosis. The
chromosome 8 to chromosome 14 c–bcl2 hyperexpression in tumor cells
is observed in Burkitt lymphoma; 3) protects them from apoptosis and thus
Philadelphia chromosome appears in ensures tumor growth and progression.
chronic myeloid leukemia, as a result of Such gene alterations occur in B–cell
c–abl proto–oncogene mutual translo- follicular lymphoma and in the small
cation between chromosomes 9 and 22; cell lung cancer.
4) amplification of oncogenes is detect- Experimental and clinical data show
ed in glioblastoma (c–erbB), lung, colon that the activation of proto– oncogenes
and pancreatic cancer (c–myc, c–ras), and the inactivation of tumor–suppres-
breast cancer (c–neu). sor genes are the main mechanism of
Genes that inhibit cell proliferation evolution of normal cells to malignan-
and have antitumor action were detect- cy. These genes are the main targets of
ed in the cellular genome. P53 and Rb the action of various chemical, physi-
are the main antioncogenes or tumor– cal or viral carcinogens. The evolution
suppressor genes. P53 gene produces of malignant tumors has a multistage
a protein of 53 kilodaltons (hence the character with initiation, promotion and
name), which plays an important role progression as its stages. Gradual accu-
in protecting against cancer. It is called mulation of lesions of genes in control
the “guardian angel of cell genome”. If of cell proliferation, differentiation and
the injury of cellular DNA is insignifi- apoptosis occurs, and the malignant tu-
cant, the p53 protein stops cell division mor progresses, i.e. the degree of malig-
until the defect is removed, but if the nancy increases.
injury is major, it initiates the cell death
(“suicide”) by apoptosis. More than a
half of human cancers are based on p53
gene mutations and p53 protein inac-
tivity. Rb gene alteration is detected

TUMORS Chapte r 8
8 . 2 . S T RU C T U R E O F T U M O R S
8.2.1. MACROSCOPIC CHARACTERISTICS OF TUMORS
The macroscopic aspect of tumors

may be different. In most cases, they
have the aspect of a round or ovoid nod-
ule, lodged in the organ’s thickness or
on its surface. They are lodged in wall
thickness or protrude into the respective
lumen in hollow and tubular organs.
The surface of the nodules may be
smooth or rough, sometimes resembling
a cauliflower.
Tumors’ size and consistency vary: Fig. 8–2. Neurofibromatosis of skin – multicen-
tric tumor, which originates from the sheath of
from microscopic to very large; from nerve fibers (from the perineurium).
soft, flaccid to hard. The color varies
depending on the structural-function-
al features of the original tissue and on
the secondary changes that occur in the
tumoral tissue (dystrophic, necrotic le-
sions, circulatory disorders, inflammato-
ry processes, etc.).
Tumors can be encapsulated, cir-

cumscribed and well-defined or can
infiltrate adjacent tissues. Numerically,
they can be unicentric or multicentric
(Fig. 8–1, 8–2, 8–3). Fig. 8–3. Cardiac myxoma with exophytic
growth; it develops from pluripotent embryonic
mesenchymal elements.
Fig. 8–1. Pulmonary chondroma – benign tu-

mor of hyaline cartilage of bronchi.

Chapter 8 TUMORS
8.2.2. MICROSCOPIC ASPECTS OF TUMORS
Microscopically, tumors are com- the ratio between them, for example, the
posed of two tissular components: pa- change of the ratio between parenchyma
renchyma and stroma. Parenchyma is and stroma, variations of number, shape
the tumor cells themselves. Stroma is and size of epithelial structures, chaotic
formed of connective tissue, contains distribution of fibrillar, cellular, vascular
blood and lymphatic vessels, nerve fi- structures etc. Tissue atypism is charac-
bers. teristic for mature, benign tumors. For
The ratio between the stroma and example, in breast fibroadenoma – a be-
parenchyma may be different; stroma nign tumor of glandular epithelium - the
predominates in some tumors (fibrous tissue atypism is manifested by presence
tumors), parenchyma - in others (histi- of proliferating, unevenly distributed
oid tumors). In some cases, the stroma glandular formations of various shapes
and parenchyma are developed evenly and sizes (Fig. 8–4), in leiomyoma – a
(organoid tumors). benign tumor of smooth muscle tissue
The tumor differs from the normal – the atypism is characterized by cha-
tissue by atypism and polymorphism. otic, unordered position of fascicles of
The atypism can be: a) morphological, muscle fibers, sometimes in whirlwinds,
b) biochemical, c) histochemical and d) with varying thickness and orientation,
antigenic. interspersed with collagen fiber fasci-
The morphological atypism can cles. The tumor cells are well differenti-
be tissular, cellular and ultrastructural. ated, reminding the original tissue cells
Tissue atypism manifests itself by (Fig. 8–5).
changing the structure of original tissue,
the arrangement of structural elements,
Fig. 8–4. Tissue atypism in breast fibroadeno- Fig. 8–5. Tissue atypism in leiomyoma (hema-
ma (hematoxylin–eosin stain; ×70). toxylin–eosin stain; ×70).
Cellular atypism manifests itself by totic activity, appearance of pathological

inegalities in the shape, volume and size mitosis, multinucleated giant cells. The
of the tumor cells and nuclei, cytoplas- intensity of nucleus staining is different
mic organelles, different ratio between (nuclear hyper– or hypochromatosis);
nucleus and cytoplasm, increased mi- the arrangement of tumoral cells is cha-

TUMORS Chapte r 8
otic, unordered etc. (Fig. 8–6, 8–7, 8–8).
Cellular atypism is observed in imma-
ture, malignant tumors.
Ultrastructural atypism reflects in-
crease of the number of ribosomes, di-
versity of form, volume and location of
mitochondria, nuclei, atypical mitosis.
Fig. 8–7. Cellular atypism in rhabdomyosarco-

ma – malignant tumor of striated muscle tissue
Fig. 8–6. Cellular atypism in undifferentiated

cancer (hematoxylin–eosin stain; ×70).
Histochemical atypism reflects
biochemical and metabolic characteris-
tics of the tumor tissue that distinguish
it from the original tissue, for example, Fig. 8–8. Cellular atypism in hepatocellular
prevalence of glycolytic, anaerobic me- carcinoma (hematoxylin– eosin stain; ×70).
tabolism enzymes and increased content
embryonic, etc.) tumor antigens appear

of nucleic acids etc.
Antigenic atypism – specific (viral, in some tumors, characteristic only to
this tumor.
8.2.3. METASTASIS AND RELAPSE OF TUMORS
Metastasis – the process of tumor

cell moving in the body, their seeding
and multiplication at distance from the
primary tumor, forming secondary tu-
moral nodules or metastases (Fig. 8–9
a, b and 8–10). It is characteristic for
malignant tumors (cancer, sarcoma and
melanoma).
Varieties of tumor metastasis:
a) Blood (hematogenous) metasta-
Fig. 8–9 a. Cancer metastases in liver – macro-
sis is a cell embolism process, which is scopic aspect.

Chapter 8 TUMORS
stream, where most are killed within 24

hours, 2) embolic stage – the tumor cells
form aggregates, surrounded by a layer of
fibrin; the cell embolus stops at the level
of precapillary arterioles and 3) implanta-
tion stage – individual tumor cells detach
from the embolus, cross postcapillary ve-
nule wall, implant in the perivascular tis-
sue and form secondary metastatic nod-
ules. Depending on the primary location
Fig. 8–9 b. Cancer metastases in liver: – micro-
of tumors and characteristics of the
scopic aspect (hematoxylin–eosin stain; ×70).
venous drainage of the affected organ,
there are several variants of hematog-
enous metastasis: a) pulmonary variant
– the primary tumor is localized in the
a lungs; the tumor cells fall in the left heart
through the pulmonary veins, and then
– in the large circulation vessels, 2) liver
variant – the primary tumor is located in
the liver; liver tumor cells fall into infe-
rior vena cava, the right heart and lungs
b
through the hepatic veins, and then – in
the left heart and great circulation ves-
Fig. 8-10. Ocular melanoma (a) with metasta-
ses in femoral bone (b).
sels, 3) vena cava variant – the primary
tumor is lodged in different areas of the
found predominantly in veins and cap- body, from which venous blood flows
illaries, rarely in arteries (Fig. 8–11). into the vena cava; tumor cells penetrate
One can follow three consecutive stages the right heart, lungs, and then can reach
the left heart and great circulation ves-
sels, 4) portal vein variant – the prima-
ry tumor is lodged in an intraabdominal
organ (stomach, intestine, pancreas, etc.);
firstly, tumor cells metastasize to the liver
through the portal vein and then reach
the right heart, lungs, left heart and great
circulation vessels. Blood metastasis is
characteristic especially for sarcomas,
melanomas, choriocarcinoma etc.
b) Lymphatic (lymphogenous) me-
Fig. 8–11. Tumor embolus in a blood vessel (he-
tastasis is characteristic for carcino-
matoxylin–eosin stain; ×70).
mas. The first metastases are lodged in
in the evolution of this process: 1) in- regional lymph nodes (satellite-lymph
vasion stage – tumor cells penetrate the nodes of the affected area). After over-
lymphatic vessels and later - the blood- coming regional lymph nodes, tumor

TUMORS Chapte r 8
cells enter the systemic circulation and
various organs and tissues.
c) Metastasis by implantation or
by contact can be observed more fre-
quently in serous membranes (e.g.
peritoneal, pleural carcinomatosis), in
the brain (through the cerebrospinal
fluid), along the nerve trunks (perineu-
ral spread of tumors, Fig. 8–12). One
Fig. 8–12. Perineural spread, by contact, of
can also meet intracanalicular spread
glandular carcinoma (hematoxylin–eosin sta-
of malignant tumors through epithe- in; ×70).
lial ducts, e.g. spread of breast cancer
ducts, urinary bladder cancer – through
through lactiferous breast ducts, spread
ureters.
of gallbladder cancer – through billiary
8.2.4. MORPHOGENESIS OF TUMORS

Relapse – reappearance of tumor in are subdivided into obligatory (turn into
the same site after surgical removal or af- cancer in most cases) and optional (turn
ter radiotherapy. It develops from cells rarely into cancer). The best examples
that may remain in the tumor site or of obligatory precancer are the congen-
from the closest lymphatic metastases. ital polyposis of the large intestine and
It is characteristic for malignant tumors the xeroderma pigmentosum, both of
(e.g. in carcinoma, sarcoma, melanoma). It hereditary nature. Optional pretumor-
is also met in tumors with locally de- al conditions include some processes of
structive growing (for example, in basalio- hyperplasias, dysplasias and dysembrio-
ma, desmoid tumor, ameloblastoma). plasias, accompanied by morphological

Tumor development can begin de restructuring of tissues and functional
novo, but, more frequently, it emerges disorders. Examples: leukoplakia, squa-
on the background of some pre-tumoral mous metaplasia and mucosal polyposis,
(precancerous or premalignant) lesions. chronic gastric ulcer, liver cirrhosis, dys-
These lesions show some pathological plasia of mucosal epitheliums, glandu-
processes, which create a high risk for lar cystic hyperplasia of endometrium,
tumor development. Pretumoral lesions chronic atrophic gastritis, etc.
8.2.5. GROWTH OF TUMORS
According to the differentiation de- atrophy); the tumor has precise limits
gree of tumors and the report towards and can be easily removed (enucleated);
the adjacent tissues, the following tumor it is characteristic for benign tumors;
growth variants are observed: b) infiltrative (invasive) – tumor
a) expansive – tumor grows slowly cells infiltrate and destroy adjacent
“from itself ”, removing and compressing normal tissue (destructive growth); in-
the nearby tissues, which gradually form vasion occurs along nerve fibers, blood
a fibroconnective capsule around the tu- and lymphatic vessels, intertissular spac-
moral node (parenchymatous elements es etc; the tumoral node does not have

Chapter 8 TUMORS
precise boundaries; it is characteristic for swelling, tumefaction), for example,

malignant tumors. nephroma, hepatoma, fibroma, angioma,
According to the number of ini- myoma, osteoma etc. This principle is
tial tumoral growth foci, tumors can be mainly used to designate benign tumors.
unicentric (one focus) and multicentric As to malignant tumors, the terms can-
(with multiple foci). cer or carcinoma, introduced by Hip-
In hollow and tubular organs, tumors pocrates (Greek “karkinos” = sea crab)
can have an exophytic growth – expan- are used for tumors of epithelial origin;
sive growth in the organ’s cavity, and sarcoma - for tumors of mesenchymal
endophytic growth– the tumor lodges origin (Greek “sarcos” = fish meat). The
in the wall thickness of the respective suffix blastoma (Greek “blastos” = ger-
cavity. m+oma) is used for malignant tumors of
Terminology of tumors: in most nervous origin, for example, neuroblas-
cases, the tumor name is formed from toma, glioblastoma, medulloblastoma.
the root of the injured tissue or organ’s The term cancer is sometimes used as a
name, plus the suffix “oma” (“oma” – generic name of all malignant tumors.
8.2.6. CLASSIFICATION OF TUMORS
I. Clinical and morphological growth (intermediate type). Their gen-

classification of tumors: a) benign, b) eral characteristic is presented in the Ta-
malignant, c) with locally destructive ble 8.1.
Table 8.1.
General characteristic of tumors
Tumors with locally
Criterion Benign tumors Malignant tumors
destructive growth
Growth rate Slow Rapid Slow
Degree of Mature,
Immature, Mature, differentiated
differentiation differentiated
undifferentiated cells cells
of tumor cells cells
Tissue, cellular
(ultrastructural,
Atypism Tissular biochemical, Tissular
histochemical,
antigenic)
Growth character
Expansive Infiltrative (invasive) Infiltrative
towards adjacent
tissues
Clear, precise
Tumor boundaries Blurred, unclear Blurred, unclear
(encapsulated)
Metastasis No metastasis Metastasis No metastasis
Recurrence No relapse Relapse Relapse
Clinical, morphological Can turn
Cannot turn benign Can turn malignant
evolution malignant

TUMORS Chapte r 8
Benign tumors have a slow develop- diate position of semi-malignant tu-
ment, remain localized, grow expansively, mors. They are formed of mature, dif-
compressing the adjacent tissues; they do ferentiated cells, with infiltrative growth,
not exert a general action on the body. therefore they may relapse, but do not
These tumors are composed of mature, metastasize. The desmoid, ameloblasto-
differentiated cells, so their histogenetic ma, craniopharyngioma can be examples
origin can always be established. They of such tumors.
differ only by tissular atypism and, usual- II. Histogenetic classification (ac-
ly, do not recur after surgery and do not cording to the original tissue) of tu-
metastasize. In some cases, benign tumors:
mors may have major clinical effects, de- 1) epithelial tumors with no specific
pending on location, such as intracranial location (non organ-specific);
or intracardiac tumors, hormonal active 2) epithelial tumors with specific lo-
tumors of endocrine glands. cation (organ-specific);
Benign tumors in parenchymatous 3) mesenchymal tumors;
organs have the appearance of encapsu- 4) melanopoietic tissue tumors;
lated, well-defined nodules, which can be 5) nervous system and meningeal
easily enucleated; they have the color of membranes tumors;
the original tissue, when sectioned. On 6) hematopoietic and lymphoid tis-
the surface of the skin and mucous mem- sue tumors;
branes, benign tumors are polyp-shaped, 7) teratomas (disontogenetic tumors).
with smooth or rough surface (cauli- III.TNM classification of tumors:
flower aspect) or nodule-shaped, with a The TNM system (tumor, nodus, me-
broader (sessile) or narrower (peduncu- tastasis) was developed by the Union for
lated) implantation base. International Cancer Control (UICC),
Malignant tumors have a fast in order to assess the stage of cancer. The

growth, infiltrative towards neighbor- TNM system has two classifications:
ing tissues and characterized by cellular TNM – pre-therapeutic clinical and
atypism. They are formed of immature, radiological classification, and pTNM
undifferentiated cells; sometimes, their - postoperative histopathological clas-
tissular origin cannot be identified. Ma- sification, based on additional findings
lignant tumors recur and metastasize, made during surgery and macro-micro-
exerting local and general effects on the scopic examination of the removed part.
body. In parenchymatous organs, malig- This staging classification is based on 3
nant tumors have the form of single or categories: T – primary tumor extension,
multiple nodules with imprecise, unclear N –absence or presence and extent of
boundaries or no boundary at all, infil- metastases in regional lymph nodes, M
trating and destroying the surrounding – absence or presence of distant metas-
tissues. Frequently, secondary changes, tases. These three components are added
like necrosis foci, hemorrhage, inflam- numbers from 0 to 4 in each category and
mation, myxomatosis, cystic cavities oc- the tumor stage is assessed, for example:
cur in malignant tumors. 1) T – primary tumor characteristic:
Tumors with locally destructive T0 – no histological signs of pri-
(invasive) growth occupy the interme- mary tumor; Tis – carcinoma in

Chapter 8 TUMORS
situ; T1, T2, T3, T4 – size and/or A decisive criterion of tumor malig-
local extension of primary tumor; nancy is the condition of lymph nodes.
2) N – condition of regional lymph The presence of lymph node metastases
nodes: N0 – microscopically, there requires a more aggressive, more radical
are no metastases in the regional therapeutic conduct towards the cases
lymph nodes, N1, N2, N3 – num- when such metastases lack. The pres-
ber and size of metastases in re- ence of distant metastases is generally a
gional lymph nodes (metastases contraindication for other surgeries than
in other than the regional lymph the palliative ones.
nodes are assessed as distant me- IV. Classification of tumors ac-
tastases); cording to the histopathological de-
3) M – absence (M0) or presence of gree of differentiation:
distant metastases (M1). All types of tumors must be histo-
For example, TNM classification of logically confirmed by biopsy. At micro-
gastric cancer: T – primary tumor: T0 scopic examination, the degree of sim-
– no evidence of tumor at histopatho- ilarity of tumor cells with their normal
logical examination, Tis – intraepithelial tissue prototype (tissue of origin) is as-
carcinoma (in situ), T1 – tumor invasion sessed, based on the general histoarchi-
of mucosa or submucosa, T2 – tumor in- tectonics, cell atypism, number of mito-
vasion of the muscular layer or subserous ses, presence of atypical mitoses, nuclear
membrane, T3 – tumor invasion of subse- pleomorphism, etc. Each parameter is
rous membrane, but without invasion of assigned a score from 1 to 4, allowing
adjacent structures, T4 – tumor invasion the inclusion in one of the following de-
of adjacent structures (spleen, transverse grees of differentiation:
colon, liver, diaphragm, pancreas, abdom- Gx – the degree of differentiation
inal wall, adrenal glands, kidneys, small cannot be established;
intestine and retroperitoneal space); N – G1 – high degree of differentiation

regional lymph nodes (regional lymph (low malignancy)
nodes of the stomach are located on the G2 – moderate degree of differentia-
large and small curvature, along the left tion (moderate malignancy)
gastric, common hepatic, lienal and ce- G3 – low degree of differentiation
liac arteries and hepatoduodenal nodes): (high malignancy)
N0 – no metastases in regional lymph G4 – undifferentiation (very high
nodes, N1 - metastases in 1–6 regional malignancy, indicating anaplastic
lymph nodes, N2 – metastases in 7–15 tumor).
regional lymph nodes, N3 – metastases In some cases, degrees 3 and 4 can be
in more than 15 regional lymph nodes merged (G3–4). The histopathological
(involvement of other intraabdominal degree of differentiation is important in
lymph nodes is classified as distant me- the estimation of the clinical severity of
tastases); M – distant metastases: M0 malignant tumors and in the evaluation
– no evidence of distant metastases, M1 of the therapeutic act. Less differenti-
– presence of distant metastases (in liver, ated tumors have a higher malignancy,
lungs, bones, brain, ovaries, supraclavicu- grow faster and are more sensitive to ra-
lar lymph nodes etc). diotherapy. Generally, higher degree tu-

TUMORS Chapte r 8
mors (G3 and G4) are more aggressive is, however, imperfect, because the his-
than the lower grade tumors; the G1 topathological degree of differentiation
tumors have the most favorable progno- may vary in different areas of the tumor
sis. Sarcomas can show a high and a low and the tumor degree can change with
degree of differentiation. This gradation its growth.
8.2.7. GENERAL AND LOCAL COMPLICATIONS OF TUMORS
Local effects: ²² cancer cachexia, determined by

ØØ deformation of organs, for exam- several factors, e.g. digestive disor-
ple, breast deformation in cancer; ders caused by tumors themselves
ØØ tumor compressive action on adja- (in esophageal, gastric, pancre-
cent tissues, for example, atrophy atic cancer), secretion of tumor
of brain tissue by compression, in necrosis factor (TNF–α), which
case of meningioma or osteoma of enhances catabolic processes in
cranial bones; the body, leading to reduction of
ØØ stenosis of tubular and hollow adipose and muscle tissue, inten-
organs through endophytic or sification of protein and energy
exophytic growth of tumors, e.g. metabolism in tumoral tissue, etc.
intestinal obstruction in colon ²² paraneoplastic syndromes – gen-
cancer, mechanical jaundice in en- eral clinical manifestations that
cephalic pancreatic cancer, pyloric cannot be directly related to local
stenosis in gastric cancer; effects of tumor or to metastasis;
ØØ pains caused by nerve compres- they disappear after tumor remov-
sion or perineural expansion of al and reappear, if it recurs. It is
cancer cells; observed in 10–15% of oncologic

ØØ destruction of normal adjacent patients.
tissues, e.g. bone fracture in my- The most important paraneoplasic
eloma or in cancer metastases in syndromes:
bones, perforation of hollow or- 1) endocrinopathies – ectopic secre-
gans (stomach, colon) in cancer; tion of hormones or hormone– like
ØØ necrotic lesions, ulcers, infarcts, substances in malignant tumors of
caused by compression or throm- some organs (tissues) that do not
bosis of vessels; have endocrine function in normal
ØØ bleeding through the erosion of conditions, for example, Cushing’s
blood vessels, for example, in uter- syndrome in small cell lung cancer
ine, lung and gastric cancers. (adrenocorticotropic hormone se-
General effects: cretion), hypercalcemia and oste-
²² non–specific symptoms: fever, oporosis in squamous lung cancer,
loss of appetite, fatigability, gener- renal cell carcinoma (secretion of
al weakness, due to absorption of parathormone–like proteins), hy-
tumor tissue destruction products poglycemia in uterine leiomyosar-
and bacterial toxins, in case of in- coma, retroperitoneal fibrosarcoma,
fected tumors; liver cancer (secretion of insulin-like

Chapter 8 TUMORS
factors), carcinoid syndrome in car- marrow with tumor infiltrates, re-

cinoid tumors of bronchi, ileum (se- duction of hematopoietic function
cretion of serotonin, which causes after chemotherapeutic or radio-
facial erythema, diarrhea, bronchial therapy treatments); erythrocytosis
and bowel spasm); (increase of the number of red blood
2) hematologic manifestations – cells) in renal cell carcinoma (ex-
phlebothrombosis (venous throm- cessive secretion of erythropoietin),
bosis), often migratory or Trous- thrombocytopenia etc.;
seaux syndrome in pancreatic cancer 3) cutaneous manifestations – acan-
(tumor cells synthesize thrombo- thosis nigra (skin hyperpigmenta-
plastic substances), DIC syndrome tion in the axillary, neck, perianal,
– in leukemia, prostate, lung, stom- inguinal areas) in gastric cancer,
ach cancers (tumor cells synthesize squamous bronchogenic cancer;
thromboplastic substances and con- 4) neurological manifestations – my-
sume the clotting factors); anemia asthenia gravis in thymus tumors,
– in various malignancies (caused peripheral neuropathy, cortical
by chronic hemorrhage, appearance cerebellar degeneration in small
of anti-erythrocyte autoantibodies, cell bronchogenic cancer, breast and
substitution of hematopoietic bone ovarian cancer.
8.3. EPITHELIAL TUMORS WITH NO SPECIFIC LOCATION

(NON- ORGAN-SPECIFIC)
This group of tumors develops from functions. They can be benign and ma-
squamous, transitional and glandular lignant.
epithelia, which do not perform specific

8.3.1. BENIGN EPITHELIAL TUMORS
Papilloma and adenoma are benign Microscopically, papilloma consists

epithelial tumors with out specific lo- of stratified squamous epithelium, pro-
cation. liferated unevenly (parenchyma) and
Papilloma develops from squamous,
stratified and transitional epithelium. It
is met on the skin and mucosa covered
with respective epithelia: oral cavity, na-
sopharynx, larynx (vocal folds), esopha-
gus, urinary bladder, cervix. Papilloma is
also observed in the excretory ducts of
exocrine glands and mammary gland.
Macroscopically, papilloma is a
spherical tumoral formation with rough
surface, dense consistency, wide or nar-
row implantation base and sizes from Fig. 8–13 a. Skin papilloma, macroscopic as-
1–2 mm to 1–2 cm (Fig. 8–13 a). pect.

TUMORS Chapte r 8
subepithelial connective tissue, rich in tract mucosas etc.). In compact organs,
blood vessels (stroma), distributed cha- adenoma appears as well- delimited, en-
otically. The epithelium forms protrud- capsulated (expansive growth) nodules,
ing papilliform proliferations on the with the color and consistency of the
skin surface. The basement membrane original tissue. On mucosal membranes,
is preserved, as well as the complexity it has the aspect of a pedunculated or
and polarity of epithelial cells (local- with a large implantation base polyp
ization of different cytoplasmic organ- (Fig. 8–14a, b). Adenoma may become
elles in the apical and basal poles of the
cell), which is characteristic for benign
tumors (Fig. 8–13 b). The corneal lay-
er is thickened (hyperkeratosis), as well
as the malpighian one (acanthosis). All
Fig. 8–14 a. Colon adenomatous polyps (adeno-

mas), macroscopic aspect.
malignant and transform into adenocar-
cinoma (glandular carcinoma).
Microscopically, the tumor shows
glandular structures of various shapes
Fig. 8–13 b. Skin papilloma, microsco-
pic aspect (hematoxylin–eosin stain; ×70). and sizes, some are cystically dilated;
tumor cells are well differentiated, ma-

these changes reflect the tissular atypism ture, reminding the original glandular
in papilloma. epithelium. The basement membrane
In cases of prolonged mechani- is intact, polarity and complexity of the
cal irritation, the papilloma may be- epithelium is preserved (Fig. 8–14b).
come malignant, squamous carcino- The following varieties of adenoma can
ma appears. Clinical manifestations
depend on the location (vocal folds,
urinary bladder, nasal cavities, cervix,
etc.). Papillomas of excretory ducts,
larynx and urinary tract are consid-
ered potential precancerous lesions.
Adenoma. It develops from glandular
epithelium. It can be found in glandular
organs (prostate, pancreas, liver, salivary,
sweat glands, mammary gland, adrenal
glands, ovaries, etc.) and at the level of
mucosas covered with glandular epithe- Fig. 8–14 b. Colon adenomatous polyps (adeno-
lium (gastrointestinal, tracheal–bron- mas), microscopic aspect (hematoxylin–eosin
chial, uterine, gallbladder and biliary stain; ×70)

Chapter 8 TUMORS
be distinguished: 1) acinar (alveolar); 2) torting and compressing the glandular

tubular; 3) trabecular; 4) papillary (vil- ducts, and pericanalicular, when the con-
lous adenoma). The last variant is more nective stroma proliferates around the
common in the colon, it is often associ- ducts. Adenomas of endocrine glands
ated with epithelial dysplasia and 30% can be hormonally active. In such cases,
of cases become malignant. The tumor different clinical syndromes, caused by
is called fibroadenoma or adenofibro- excess of the respective hormones, devel-
ma, in cases when the connective stroma op in patients, e.g. acromegaly appears in
prevails over the glandular parenchyma somatotropic pituitary adenoma, Cush-
in the adenoma. The fibroadenoma is ing’s syndrome appears in cortical ad-
the most common benign tumor of the enoma of adrenals with ACTH hyper
mammary glands and can have two his- secretion, hyperglycemic syndrome - in
tological variants: intracanalicular, when pancreatic insulinoma derived from beta
the connective tissue proliferates, dis- cells with secretion of insulin etc.
8.3.2. MALIGNANT EPITHELIAL TUMORS

The general name of malignant ep- usually of epithelium dysplasia, that
ithelial tumors without specific location evolves into cancer.
is cancer or carcinoma. Macroscopically, it usually has the
Cancer is met more frequently aspect of a tumor node with no precise
than other malignancies. It can devel- limits, infiltrating the surrounding tis-
op from squamous stratified epithe- sues (invasive growth). It has a flaccid or
lia of transitional or glandular type. It dense consistency; it is whitish on sec-
is characterized by cellular and tissue tion, located in the depth or on the sur-
atypism, infiltrative (invasive) growth, face of compact organs, on the surface
predominantly metastasis and relapse. (exophytic growth) or wall thickness

The first lymphogenous cancer metas- (endophytic growth) – in hollow and
tases emerge in regional lymph nodes, tubular organs (Fig. 8–15, 8–16,8–17,
but, as tumor progresses, hematogenic 8–18, 8–19). Cytokeratins, a marker of
and implantation metastases may also epithelial tumors (cytokeratins are pres-
develop. Cancer often appears on the ent in the cytoskeleton of all true epithe-
background of precancerous processes, lia), stand out in cancer cells.
Fig. 8–15. Laryngeal carcinoma. Fig. 8–16. Fungoid gastric carcinoma

(mushroom aspect).

TUMORS Chapte r 8
tous (medullary), 7) fibrous (scirrhous),
8) trabecular (solid), 9) dimorphic.
1) Carcinoma in situ (pre-invasive,
intraepithelial): cellular atypism and
polymorphism, pathological mitoses are
observed only in the epithelial layer; the
vertical stratification, which is charac-
teristic for the normal squamous strat-
ified epithelium, is blurred, unclear and
the tumor invasion does not exceed the
Fig. 8–17. Peripheral lung cancer – macrosco- basement membrane, it remains intact
pic aspect. (Fig. 8–20); it turns invasive (infiltra-
tive) in dynamics.
Fig. 8–18. Diffuse gastric cancer with endophy-

tic growth – macroscopic aspect.
Fig. 8–20. Carcinoma in situ (hematoxylin–eo-

sin stain; ×70).

2) Squamous (epidermoid or squa-
mous cell) carcinoma originates from
squamous (skin, oral cavity, esophagus,
pharynx, larynx, cervix, vagina) or tran-
sitional epithelium (renal pelvis, ureters,
urinary bladder), as well as from glandu-
lar epithelium with previous squamous
metaplasia (bronchi, endometrium, gall-
Fig. 8–19. Cervical cancer – macroscopic as- bladder, etc.). The squamous carcinoma
pect. is made up of fascicles of atypical epi-
Classification and general character- thelial cells, which invade the adjacent
istics of cancer tissue; it has two variants: with and
The following cancer forms are dis- without cornification (or keratiniza-
tinguished: 1) in situ (pre–invasive), 2) tion); “keratin pearls” – an accumulation
squamous cell (epidermoid) cornified and of keratin masses in the center of tumor
non-cornified, 3) glandular (adenocarci- cell islands, reflecting the keratinization
noma) 4) muciparous (colloid), 5) undif- ability of the epithelium, are observed in
ferentiated (anaplastic), 6) parenchyma-

Chapter 8 TUMORS
cornified squamous cancer (Fig. 8–21a, lous or mushroom aspect, usually, with
b and 8–22); the mitosis rate is higher ulcerations; the proliferative transitional
in non-cornified cancer; urothelial epi- epithelium is not less than 7 cell layers
thelium carcinomas have a papillary, vil- thick.
a b
Fig. 8–21 a, b. Squamous (epidermoid) keratinizing carcinoma with keratin pearls (hematoxylin–
eosin stain; ×70).
3) Glandular carcinoma (adeno-
carcinoma) derives from the prismatic,
cylindrical or cubic epithelium of the
mucous membranes and of glandular
organs (stomach, intestine, uterus, lungs,
liver, pancreas, prostate, salivary, sudorif-
erous, mammary and endocrine glands
etc.). It can adopt the following histo-
logical forms: tubular (Fig. 8–23a), alve-

olar or papillary (Fig. 23b). According to
the degree of differentiation, adenocar-
Fig. 8–22. Squamous (epidermoid) non–kera-
cinoma can be highly, moderately and tinizing carcinoma (hematoxylin–eosin stain;
low differentiated. The gland forming ×70).
ability decreases considerably in low dif-
a b
Fig. 8–23. Glandular carcinoma (adenocarcinoma): tubular (a) and papillary (b) (hematoxylin–
eosin stain; ×70).

TUMORS Chapte r 8
ferentiated tumors and it is difficult to the stomach, but it can also be met in
detect glandular structures at the micro- other organs.
scopic examination. 5) Undifferentiated (anaplastic)
4) Muciparous carcinoma (colloid) carcinoma - the origin of the tumor
originates from glandular epithelium; cannot be identified. Histological vari-
tumor cells produce large amounts of ants: a) small cells, b) large cells, c) gi-
mucus. Macroscopically, it has the as- ant cells. Tumor cells are monomorphic
pect of a mucinous or colloid mass (ge- and do not form any structures, stroma
latinous appearance). Cancer cells accu- is poor (Fig. 8–25); it is a highly malig-
mulate vacuoles of mucin and may take nant form of cancer that develops early
the shape of “a signet ring” (Fig. 8–24). metastases.
This form of cancer is most common in
Fig. 8–24. Muciparous carcinoma (hemato- Fig. 8–25. Undifferentiated cancer with small
xylin–eosin stain; ×70). cells (hematoxylin–eosin stain; ×70).

6) Parenchymatous (medullary) tissue or the bone marrow; it is a form
carcinoma: parenchyma prevails in the of undifferentiated adenogenic cancer,
tumor, the stroma is poor; it has soft which develops early multiple metasta-
consistency and reminds the cerebral ses (Fig. 8–26 a, b).
a b
Fig. 8–26 a, b. Parenchymatous (medullary) carcinoma: a-schematic representation, b-microsco-

pic pattern (hematoxylin–eosin stain; ×70).

Chapter 8 TUMORS
7) Fibrous (scirrhous) carcinoma: of connective tissue (Fig. 8–27a, b); the

stroma prevails in the tumor; thin cords tumor has a thick consistency; it is dis-
of atypical, hyperchromic tumor cells are tinguished by high malignancy and early
observed among the abundant fascicles metastases.
a b
Fig. 8–27 a, b. Fibrous (scirrhous) carcinoma: a-schematic representation, b-microscopic pattern

8) Trabecular (solid) carcinoma: (Fig. 8–28 a, b); it is a form of undiffer-

stroma and parenchyma are represent- entiated cancer, with rapid growth and
ed uniformly; fascicles of tumor cells early metastases.
alternate with fibroconnective fascicles
a b
Fig. 8–28 a, b. Trabecular (solid) carcinoma: a-schematic representation, b-microscopic pattern

9) Dimorphic carcinoma: it is a circulatory and inflammatory lesions ap-
mixed form of cancer, where glandular pear in cancerous tumors. These lesions
and squamous structures are observed. are more marked and appear earlier in
Usually, secondary dystrophic, necrotic, tumors with higher malignancy.

TUMORS Chapte r 8
ESSENTIAL TERMS
on the subject “NON-ORGAN-SPECIFIC EPITHELIAL TUMORS”
adenocarcinoma expansive growth papilloma

adenoma glandular cancer paraneoplastic syndrome
atypism invasive growth relapse
blastoma keratin pearl scirrhous cancer
cancer medullary cancer solid cancer
cancer in situ metastasis squamous cancer
carcinoma muciparous (colloid) cancer TNM classification
dimorphic cancer neoplasm tumor
endophytic growth obligatory pre-cancer undifferentiated cancer
exophytic growth optional pre-cancer
TESTS
on the subject "NON-ORGAN-SPECIFIC EPITHELIAL TUMORS"
SET I.
Multiple-choice questions with one cor- 3. Lymphogenic metastases are a manifestation
rect answer. of all the below-listed processes, except for:
1. Which of the listed signs is typical for ben- a) tissue embolism;
ign tumors: b) malignant tumors;
a) expansive growth; c) cancer;

b) growth with formation of sec- d) invasive growth;
ondary nodules; e) benign tumors.
c) diffuse growth; 4. Which tissues does cancer develop from:
d) invasive growth; a) connective tissue;
e) metastasis. b) adipose tissue;
c) striated muscular tissue;
2. Which of the listed pathological processes
d) bony tissue;
is characterized by disturbance of the epi-
e) epithelial tissues.
thelium proliferation and differentiati-
on processes, with appearance of cellular 5. Which of the listed signs is characteristic
atypism and without alteration of base- for scirrhous cancer:
ment membrane; a) prevalence of parenchyma over
a) metaplasia; stroma;
b) aplasia; b) prevalence of stroma over paren-
c) hyperplasia; chyma;
d) dysplasia; c) homogeneous development of
stroma and parenchyma.
e) anaplasia.

Chapter 8 TUMORS
SET II.
Multiple-choice questions with 2, 3 or a) adenoma;

more correct answers. b) fibroma;
1. Which of the listed signs are typical for ben- c) papilloma;
ign tumors: d) adenocarcinoma;
a) tissue atypism, rapid, infiltrative e) squamous cancer.
growth; 4. Which of the listed signs characterize ade-
b) expansive, slow growth; noma:
c) tissue atypism, slow growth; a) develops from stratified squamous
d) tissue atypism, invasive growth; epithelium;
e) slow growth, metastasis. b) develops from glandular epithe-
2. Which of the listed signs characterize tumor lium;
metastasis: c) is a benign tumor;
a) circulation of cells by blood and d) recurs frequently;
lymphatic stream; e) metastasizes hematogenously.
b) emergence of new node on the ex- 5. Which of the listed signs are typical for cancer:
tirpation site; a) it is a malignant tumor of mesen-
c) infiltrative growth; chymal origin;
d) implantation of tumor cells; b) metastasizes more frequently by
e) transformation of parenchymato- lymphogenous way;
us cells in tumoral ones. c) develops from epithelial tissue;
3. Which of the listed tumors develop from d) has an expansive growth;
glandular epithelium: e) cellular atypism.
SET III.
The classification tests include 2–4 sub- 2. Which of the morphological manifestations
jects and a series of answers. Indicate which of tumor characterize:
answers are correct for each separate sub- I – tissue atypism;
ject. II – cellular atypism;
1. Which of the listed signs are characteristic a) presence of pathological mitosis;
for: b) chaotic location of fibrillar struc-
I – benign tumors; tures in tumors;
II – malignant tumors; c) tumor cells are mature, differen-
a) frequent relapse after tumor’s re- tiated, form structures that are
moval; unusual for the respective tissue
b) the tumor, usually, does not recur (organ);
after removal; d) change of the connection between
c) marked cellular atypism; stroma and parenchyma of tumor;
d) tumor consists of mature, diffe- e) tumor cells differ significantly
rentiated cells; from the original tissue cells;
e) tumoral cachexia is characteristic; f ) tumor cell anaplasia.
f ) tumor metastasis is typical; 3. Which of the listed morphological processes
g) compression and atrophy of adja- characterize:
cent tissues.

TUMORS Chapte r 8
I – expansive growth of tumors; sas covered by prismatic epithe-
II – invasive growth of tumors; lium;
a) tumor cells invade adjacent tissu- e) tumor cells preserve the cornifica-
es; tion ability;
b) tumor does not have clear limits; f ) develops from glandular epithe-
c) tumor node can be removed (enu- lium;
cleated) easily; g) develops from stratified squamous
d) tumor cells destroy blood and epithelium.
lymphatic vessel walls; 5. Which version of tumor growth towards
e) the tumor has usually a well–defi- the lumen of hollow organs is listed in the
ned, node-like form; examples below:
f ) compressed adjacent tissues form I – endophytic growth;
a pseudocapsule. II – exophytic growth;
4. Which of the listed morphological signs are a) urinary bladder papilloma;
characteristic for: b) adenomatous polyp of the colon;
I – squamous cancer; c) scirrhous gastric cancer;
II – adenocarcinoma; d) peribronchial lung cancer;
a) typical location – gastrointestinal e) intrabronchial lung cancer;
mucosa; f ) polypoid or fungoid gastric can-
b) typical location – skin; cer;
c) tumor cells preserve the ability of g) cardiac myxoma with growth in
left atrium cavity;
mucus secretion;
h) cardiac rhabdomyoma with
d) it is preceded by squamous meta-
growth in left ventricle wall
plasia of epithelium on the muco-
thickness.

Daily practice cases are presented with Question:

clinical and morphological data from cli- What kind of tumor has developed in this case:
nical histories and/or from necropsy proto- a) adenoma;
cols. Each subject includes simple or multi- b) papilloma from transitional epi-
ple - answer questions, with 1, 2 or more thelium;
correct answers. c) cancer in situ;
1. The biopsy of a tumoral formation with a d) cancer from transitional epithe-
diameter of 0,8 cm, papillary surface, re- lium;
sembling cauliflower, was collected at the
e) squamous cancer.
endoscopic examination of the urinary
bladder. Microscopically, the tumor con- 2. The histological examination of an endosco-
sists of branched papillae, covered with se- pic biopsy from the stomach revealed signs
veral layers of transitional-type epithelial of cellular and tissue atypism and cancer
cells; the basement membrane is unaltered. diagnosis was established.

Chapter 8 TUMORS
Question: tion of the cervix. The microscopic exa-

mination of biopsy revealed thickening of
Which of the listed signs play a decisive role in
the stratified squamous epithelium, basal
the respective diagnosis: cells proliferation, marked atypism and
a) gastric mucosa glands vary in shape polymorphism of epithelial cells, hyper-
and size; chromatosis of nuclei, numerous patholo-
b) gastric glands are arranged chaoti- gical mitoses; the basement membrane is
cally; not crossed by neoplastic cells.
c) gastric glands are covered by
Question:
polymorphic cells with large,
hyperchromic nuclei and an incre- What diagnosis should be made in this case:
ased number of nucleoli, atypical a) cancer in situ;
mitoses; b) noncornified squamous cancer;
d) gastric glands are located very clo- c) scirrhous cancer;
se to each other; d) adenocarcinoma;
e) sometimes, epithelial cells are ar- e) epithelial dysplasia.
ranged in several rows. 5. Biopsy was collected from a suspect site of
3. The histological examination of a malig- bronchial mucosa, of a 67-year-old pati-
nant tumor of the mammary gland reve- ent with the clinical diagnosis of chronic
aled that the tumor consists of undifferen- bronchitis, pneumosclerosis and cardio-
tiated, atypical cells of epithelial origin, pulmonary failure. Histologically, cellular
which form trabeculas, separated by fibro- and tissue atypism, “keratin pearls” struc-
connective fascicles; the correlation betwe- tures were revealed.
en cells and stroma is 1:1.
Question:
Question:
What pathological process develops in the gi-
Which histological variant of cancer is in this ven patient:

case: a) polypoid chronic bronchitis;
a) adenocarcinoma; b) cancer in situ;
b) squamous cancer; c) squamous metaplasia of bronchial
c) scirrhous cancer; epithelium;
d) solid cancer; d) cornified squamous cancer;
e) medullary cancer. e) noncornified squamous cancer.
4. Biopsy was collected from a 47-year-old
patient, with erosion of the vaginal por-

TUMORS Chapte r 8
8.4. MESENCHYMAL TUMORS
Mesenchymal tumors are the tu- Mostly, they have a monophasic struc-
mors that develop from tissues of mes- ture, formed from a single tissue, but
enchymal origin: lax and dense connec- they also may be polyphasic with more
tive tissue, white and brown adipose tissular components (called mesenchy-
tissue, blood and lymph vessels, smooth mal). Mesenchymal tumors may be het-
and striated (the cardiac one included) erotopic, consisting of a tissue, which is
muscular tissue, cartilaginous, bony tis- not characteristic for the given organ,
sue, synovial and serous membranes. for example, lung osteoma, retroperito-
The pluripotent mesenchymal cell is neal synovioma etc. Usually, they have a
the development source of these tumors. histioid structure, with prevalence of pa-
Generally, the mesenchymal tumors are renchymatous elements in their compo-
more infrequent than the tumors of ep- sition; the stroma is weakly developed.
ithelial origin; they have no specific lo- Mesenchymal tumors are subdivided
cation and can be found in any organ. into benign and malignant (Table 8.2).
Table 8.2.
Classification of mesenchymal tumors
Tissue of origin Benign tumors Malignant tumors
Fibroma (soft, hard)
Dermatofibroma (histiocytoma) Fibrosarcoma
Connective tissue
Elastofibroma Malignant histiocytoma
Fibromatosis (desmoid tumor)
Lipoma Liposarcoma

Adipose tissue
Hibernoma Malignant hibernoma
Leiomyoma Leiomyosarcoma
Muscular tissue
Rhabdomyoma Rhabdomyosarcoma
Hemangioma (capillary, venous, Hemangiosarcoma
cavernous, arterial) (malignant
Blood vessels
Hemangiopericytoma hemangioendothelioma or
Glomangioma hemangiopericytoma)
Lymphatic vessels Lymphangioma Lymphangiosarcoma
Osteoma (compact, spongy)
Osteosarcoma (osteoblastic
Bone tissue Osteoid osteoma (benign
or osteolytic)
osteoblastoma)
Chondroma (ecchondroma,
Cartilaginous tissue enchondroma) Chondrosarcoma
Benign chondroblastoma
Mesothelial tissue Benign mesothelioma Malignant mesothelioma
Synovial sarcoma
Synovial membranes Benign synovioma
(malignant synovioma)

Chapter 8 TUMORS
8.4.1. BENIGN MESENCHYMAL TUMORS
Benign tumors of mesenchymal ori- lated (expansive growth) tumor nodule,

gin, like all benign tumors, have a slow, of few mm to 10–15 cm of diameter,
expansive growth, they are well defined, whitish, soft or hard consistency. One
encapsulated, microscopically composed distinguishes soft fibroma, where cel-
of mature, differentiated cells, similar lular elements prevail and hard fibro-
to the tissue of origin; they are charac- ma, formed predominantly of colla-
terized only by tissue atypism. These gen fibers. On section, it has a fibrillar
tumors grow slowly, can reach large di- structure, an obvious tissue atypism; the
mensions, do not recur, nor metastasize. connective fascicles are arranged chaoti-
Dystrophic, necrotic lesions, circulatory cally, sometimes in eddies (Fig. 8–29 a).
disorders, edema, myxomatosis, dystro- Microscopically, the tumor consists of
phic calcinosis etc. can occur in all the connective tissue cells (fibroblasts and
benign mesenchymal tumors. Also, mes- fibrocytes) and collagen fibers, arranged
enchymal tumors subdivide in soft tissue in unevenly thick and disorderly orient-
tumors (nonskeletal) and hard tissue tu- ed fascicles (Fig. 8–29 b).
mors (osteocartilaginous). Fibroma location may be the most
Fibroma is a benign tumor that diverse, but it is found more frequently
derives from connective tissue. Macro- in skin, uterus, mammary gland, fascias,
scopically, it is a well–defined, encapsu- tendons. Manifestations and clinical im-
portance depend on the localization.
a b
Fig. 8–29 a, b. Fibroma: a – macroscopic aspect, b – microscopic pattern (hematoxylin–eosin stain;

×70).
Elastof ibroma is a nodular tumor, ties. Macroscopically, it has the form of a
which can reach 10–15 cm in diameter, and small dimension, brown colored tumoral
is usually located in the subscapular and node, with a diameter up to 1 cm, which
interscapular regions. It is found in older protrudes above the skin. Microscopical-
people, frequently women. Microscopi- ly, it consists of two cell types (fibroblasts
cally, it consists of fibrous tissue, where the and histiocytes), fascicles of collagen fibers
elastic fibers prevail (stained with orcein). and a large number of blood capillaries.
Histiocytoma (dermatof ibroma) is locat- Histiocytic cells contain lipid inclusions
ed in the skin, subcutaneous tissue, most (xanthomatous cells), hemosiderin gran-
commonly on the level of lower extremi- ules (siderophages), which stain brown

TUMORS Chapte r 8
the tumor; giant multinucleated cells tra-abdominal desmoid - in the humerus,
(Touton cells) are met. The Pearls reac- chest wall, femur, spine region.
tion (highlights hemosiderin) is used for Lipoma is a benign tumor composed
the purpose of a differential diagnosis. of adipose tissue. Macroscopically, it is
Fibromatoses are tumors of fibro- an oval tumoral nodule of soft consis-
connective origin, with locally invasive tency, well–defined, encapsulated and
growth. They are met in fascias, aponeu- yellow on section, lobulated (Fig. 8–31a).
roses. The microscopic structure is iden-
tical to the fibromas one, but does not
have a capsule and infiltrates the adjacent
tissues. Variants: desmoid, palmar, plantar,
penile fibromatosis.
Desmoid tumor (desmoid) is the most
common variant of fibromatosis and is
a part of the group of locally destructive
tumors. It is distinguished by infiltra-
tive growth, although, by its histological
structure, the tumor is mature (cellular
atypism, polymorphism and mitoses are Fig. 8–31 a. Lipoma – macroscopic aspect.
missing). According to the location, there
Microscopically, the tumor is com-
are three varieties of desmoid: abdominal,
intra-abdominal and extra-abdominal. posed of fat cells (adipocytes) of different
More frequently, abdominal desmoid is sizes, their nucleus is shifted to the cell
met in women, in the anterior abdominal periphery; the cytoplasm is a massive lip-
wall, especially in striated muscles, during id vacuole; the stroma is usually poor and
pregnancy and postpartum. The tumoral forms thin fibrous septa, containing blood
node does not have precise limits, infil- vessels (Fig. 8–31b). In some cases, the

trating and dissociating adjacent muscle
fibers, where dystrophic changes occur
(Fig. 8– 30). Desmoid recurs frequently
after surgical removal, due to the invasive
nature. The intra-abdominal desmoid is
observed in mesentery, pelvis, and the ex-
Fig. 8–31 b. Lipoma – microscopic aspect (he-

matoxylin–eosin stain; ×70).
tumor has a rich stromal, fibroconnective
component (fibrolipoma), in others – a
vascular component (angiolipoma).
Fig. 8–30. Desmoid tumor (Masson’s trichrome Lipoma can reach very large dimen-
stain; ×70). sions (several kilograms). It is met, more

Chapter 8 TUMORS
frequently, in subcutaneous adipose tis- same time with the proliferation of the
sue, mediastinum, retroperitoneal space, fibroconnective stroma. Leiomyoma is
mesentery, epiploon, mammary gland; the most common uterine tumor, which
it can also be located intramuscularly. usually increases during pregnancy and
Hibernoma is a benign tumor, which decreases in the menopause, due to the
is derived from brown adipose tissue fact that it is sensitive to estrogens.
(it is also called brown lipoma). It con- Macroscopically, the nodules are
sists of cells with vacuolated cytoplasm well-defined, encapsulated, of yellow-
(multilocular adipocytes); the nucleus is ish– whitish color. The consistency of
in the centre of the cell; vacuoles are fat nodules is usually hard, but it can be lax
droplets rich in lipochromes (Fig. 8–32). in case of secondary changes - hemor-
Macroscopically, the tumor nodule has rhages, edema, necrosis foci and myx-
a brown-yellowish color. The tumor can omatosis. The uterine fibromyoma is
usually multiple, the tumor nodules are
located submucously, intramurally or
subserously and can reach giant sizes.
On section, they have a fibrillar struc-
ture, muscular and connective fascicles
are distributed chaotically, in eddies (Fig.
8–33). Microscopically, the leiomyoma-
tous tumor nodule consists of fascicles
of smooth muscular fibers, arranged dis-
orderly and unevenly, interspersed with
Fig. 8–32. Hibernoma (hematoxylin–eosin sta-

in; ×70).
be localized in the interscapular region,
mediastinum and neck area – the regu-

lar sites of brown adipose tissue in hu-
mans. This tissue is more abundant in
infants and is observed exceptionally in
the adults. Hibernoma is observed more
frequently in women of advanced age, in
the interscapular region.
Myomas are benign tumors of mus- Fig. 8–33. Uterine leiomyoma– macroscopic as-
cular origin, which subdivide in leiomy- pect.
omas and rhabdomyomas. collagen fiber fascicles and connective
Leiomyoma is a benign tumor of tissue cells, also distributed chaotically
smooth muscle tissue. Most frequently, (tissue atypism). In order to differenti-
it is found in the uterus, but it is also ate fibroleiomyoma from fibroma, pi-
observed in the digestive tract, urinary crofucsin stain (van Gieson’s method) is
bladder, prostate, etc. It develops from applied: the collagen fibers stain red and
smooth muscle itself or from blood ves- the leiomiocytes – yellow; collagen fibers
sel walls. The name of fibroleiomyoma only are detected in fibroma. One of the
is more correct, as the proliferation of more commonly observed uterus fibro-
muscular parenchyma takes place at the leiomyoma complications is the uterine

TUMORS Chapte r 8
bleeding (metrorrhagia). Leiomyoma Microscopically, it consists of striated
can transform into leiomyosarcoma. muscle cells of various shapes and sizes
Rhabdomyoma is a benign tumor (Fig. 8–35), with vacuolated sarcoplasm,
that derives from striated muscles and due to high content of glycogen. The
is found predominantly in the myocar- diagnosis is confirmed using techniques
dium (Fig. 8–34), skeletal musculature that highlight the transversal striation of
and tongue. It is a relatively rare tumor. myocyte sarcoplasm.
Fig. 8–34. Myocardial rhabdomyoma– macro- Fig. 8–35. Rhabdomyoma (hematoxylin–eosin

scopic aspect. stain; ×70).
Hemangiomas are benign tumors
that derive from blood vessels. All the
vascular wall elements can participate
in the formation of hemangioma. These
tumors occupy an intermediate position
between hamartoma (congenital malfor-
mations) and true tumors. The follow-

ing variants of hemangioma are distin-
guished: capillary, venous, cavernous and
arterial, glomangioma, benign hemangio-
pericytoma. Capillary hemangioma is
Fig. 8–36. Capillary hemangioma (hemato-
composed of capillary–type vessels of xylin–eosin stain; ×70).
various sizes; their wall is lined by endo-
thelial cells (Fig. 8–36). It is met, more gers’ level, especially in the nail area.
frequently, in children’s skin, mucosa of Macroscopically, it is a small, bluish,
the digestive tract, liver. The tumor nod-
ule is red or cyanotic, with smooth or
papillary surface. Cavernous hemangioma
has a spongy structure and is composed
of large vascular, dilated cavities of dif-
ferent sizes, interconnected, filled with
blood, lined by endothelial cells (Fig.
8–37). It can be found in the liver (Fig.
8–38 a and 8–38 b), skin, spongy bones,
skeletal muscles etc.
Glomangioma (glomus tumor) is Fig. 8–37. Cavernous hemangioma (hemato-
observed more frequently at the fin- xylin–eosin stain; ×70).

Chapter 8 TUMORS
often painful nodule. Microscopically, fibers. Argyrophilic fiber impregnation

it is formed of anastomosed vessels, in and PAS reaction for carbohydrates are
applied for differential diagnosis with
capillary hemangioma. These tumors
can recur and therefore, according to
some views, are considered malignant.
Lymphangioma is a tumor derived
from lymphatic vessels and found es-
pecially in children. It is analogous to
hemangioma. It lodges in the cervical
area, buccal mucosa, tongue and mes-
entery. The most common variant is
the cavernous or cystic lymphangioma,
Fig. 8–38 a. Cavernous hemangioma of liver–
where cavities of different sizes, filled
macroscopic aspect.
with lymph and lined with endothe-
lium, are observed. Macroscopically, it
has the form of a nodule or of diffuse
thickening of an organ. It can mani-
fest itself by increased size of tongue or
lips – macroglossia and macrocheilia.
Chondroma is a benign tumor from
cartilaginous tissue (Fig. 8– 39). It is
met more frequently in the limb bones
(phalanges of hands and feet), pelvis,
ribs, vertebrae, but it may also be lodged
extraosseously, especially in lungs. Mac-
Fig. 8–38 b. Cavernous hemangioma of liver–

microscopic aspect (hematoxylin–eosin stain;
roscopically, it is a whitish-bluish, well–
x50). defined tumor nodule of dense consis-
tency, reminding the hyaline cartilage.
the form of slits lined with endothelium, In the bones, it may be located on the
surrounded by epithelioid cell sheaths, surface of bone (ecchondroma) or in-
reminding the glomic cells; the tumor is traosseously (enchondroma). Micro-
richly innervated.
Benign hemangiopericytoma lodg-
es more frequently in the skin, rare-
ly – in soft tissues of the limbs, trunk
and in omentum. Macroscopically, the
reddish nodule has dense consistency
and is well–defined. Microscopically, it
is formed of capillaries and sinusoids,
lined by endothelium and surrounded
by sheaths of elongated cells, called peri-
cytes; cellular sheaths, in their turn, are
interwoven by a network of argyrophilic Fig. 8–39. Chondroma (hematoxylin–eosin sta-
in; ×70).

TUMORS Chapte r 8
scopically, it consists of hyaline carti- adolescents and young adults. It has
lage; cells are arranged chaotically in the small dimensions up to 1 cm. Location
ground substance. may be the most diverse, but more fre-
Benign chondroblastoma is a benign quently - in the femoral bone, humerus,
chondrogenic tumor, located more fre- tibia, vertebrae. Microscopically, it con-
quently in the humerus, tibia and femur. sists of osteoid anastomosed trabeculas,
It is usually found in young people, in surrounded by reactive bone tissue at the
the second decade of life, when skeletal periphery.
growth is not finished yet. Microscop- Benign synovioma is a benign tumor
ically, it contains cellular masses com- that develops from synovial elements of
posed of chondroblasts with varying tendon sheaths and tendons. It is met,
degrees of differentiation, arranged in more frequently, in the knee joint area.
the intercellular matrix, formed of chon- Its microscopic structure is polymor-
droid tissue. phic, with elongated cells, similar to
Osteoma is a benign tumor from os- fibroblasts, synovial cells, forming pseu-
seous tissue. It is found in flat, tubular doadenomatous structures, and giant
bones and, more frequently, in the crani- multinucleated cells. The tumors can
al bones, paranasal sinuses. The extraos- relapse.
seous location may be in the tongue, Benign mesothelioma is a benign
mammary gland. Microscopically, it has tumor from mesothelium. It affects the
a structure of spongy or compact bone serous membranes, especially the pleu-
tissue; the osseous trabeculas are ar- ra. Macroscopically, it has the aspect of
ranged disorderly. It may have an exo- a tumor nodule, of whitish color and
phytic growth on the surface of the bone thick consistency. Microscopically, it is
(exostosis) or endophytic, intraosseous identical to soft (cellular) fibroma. The
growth (enostosis). mesothelial origin of tumor cells can be

Benign osteoblastoma or osteoid oste- demonstrated only in cell cultures.
oma is met, more frequently, in children,
8.4.2. MALIGNANT MESENCHYMAL TUMORS
Malignant tumors of mesenchymal atypism. Sarcoma’s malignancy amplifies

origin are called sarcomas. along with the similarity decrease of tu-
They are characterized by cellular and mor cells with the original ones and is
tissue atypism, rapid, infiltrative growth, in direct proportion to the rate of mito-
so they do not have precise boundaries, sis (10 and more mitoses in a visual field
are not delimited by surrounding tissues, of 40-lens). Early circulatory disorders
are not encapsulated; macroscopically, (hemorrhages), edema, dystrophic and
the appearance of the tumor mass is of necrotic lesions, myxomatosis, cystic cav-
fish meat (hence the name in Greek sarcos – ities develop in all sarcomas. Sarcomas
meat), of whitish color and flaccid consis- recur and metastasize more frequently
tency. Microscopically, it is characterized through the blood; the first metastases
by cellular, marked polymorphism and emerge in the lung or liver. Sarcomas are

Chapter 8 TUMORS
relatively rare tumors and constitute 1% and trunk, more rarely – in the internal
of all malignant tumors. More than two organs (Fig. 8–40 a, b). Microscopical-
thirds of sarcomas are localized in the ly, it consists of polymorphic, fusiform,
femoral area, scapular girdle and retro- fibroblastic-type immature cells and an
peritoneal space. The forecast (progno- insignificant quantity of collagen fibers;
sis) of sarcomas depends primarily on the tumor has a histioid structure (cellu-
the histopathological degree of differen- lar elements prevail), relatively uniform,
tiation and the tumor stage, but also on although increased, hyperchromic nuclei
the size and depth of the tumor process and single atypical mitoses are observed;
(the prognosis is worse in larger dimen- neoplastic cells are usually arranged in
sions and deeper location in the tissue). disorderly-oriented fascicles. Vimentin
Fibrosarcoma is a malignant tumor of is detected in the tumor cells, at immu-
the connective tissue, more frequently nohistochemical examination. The prog-
located in the subcutaneous tissue and nosis depends on the tumor stage and its
in the depth of soft tissues of the limbs extension at the moment it was detected.
a b
Fig. 8–40 a, b. Fibrosarcoma: a – macroscopic aspect, b – microscopic pattern (hematoxylin – eosin

stain; ×70).
Malignant histiocytoma lodges more frequently in lungs (up to 87%) and
frequently in lower limbs and retroperi- lymph nodes (30%).
toneal tissue, where it can reach large Liposarcoma is a malignant tumor
sizes (10–15 cm). It is currently consid- derived from adipose tissue, from pre-
ered the most common malignant tu- cursor cells of adipocytes. It consists of
mor of soft tissues in adults. Microscop- poorly differentiated fat cells, with un-
ically, it is formed from histiocytic and even fat content; cells with homogeneous
fibroblastic cells, xanthomatous cells and eosinophilic cytoplasm, without lipids
Touton-type giant multinucleated cells; or with a small amount of them, bizarre,
cellular and nuclear marked atypism monster, hyperchromic nuclei are ob-
and polymorphism, multiple mitoses, served (Fig. 8–41). More frequently, it
including atypical ones, are observed. is met in subcutaneous adipose, retro-
The most common histological form peritoneal, mediastinal tissues. Necrotic
is fibrous histiocytoma with dimorphic lesions, myxoid degeneration of tumor
cellular component – elements of fibro- stroma are characteristic. Histological
blastic and histiocytic type. Metastases variants of liposarcoma: predominant-
are observed in 40–50% of cases, more ly highly-differentiated, predominant-

TUMORS Chapte r 8
posarcoma. It can develop by malignant
transformation of benign muscle tumor
(leiomyoma) or as a malignant tumor
from the start. It is composed of muscle
cells with a little differentiation, with an
obvious cellular and nuclear polymor-
phism, some big, monstrous, hyperchro-
mic nuclei, pathological mitoses; the
connective stroma is weakly developed.
An important criterion of the degree of
malignancy is the number of mitosis.
Fig. 8–41. Liposarcoma (hematoxylin–eosin
Immunohistochemically, actin is detect-
stain; ×70).
ed in tumor cells.
ly myxoid (embryonic), predominantly Rhabdomyosarcoma is a rare malig-
round cell and predominantly polymor- nant tumor that originates from striated
phocellular. Differentiated liposarcoma muscular tissue. It is met in children on
presents slow growth and late metasta- the head, neck, retroperitoneal tissue, in
sis; the undifferentiated liposarcoma de- adults – in the limbs. Microscopically, it
velops early metastases. consists of stellate and polymorphic fu-
Malignant hibernoma (fetal lipo- siform cells, some of them with trans-
ma) has the same location as the be- versal striation. The certain diagnosis
nign hibernoma. Histologically, a can be established by desmin and my-
marked polymorphism of multiloc- osin highlighting in the tumor cells, on
ular lipocytes is observed. Metasta- application of immunohistochemical re-
ses are rare. It is considered a variant actions.
of polymorphocellular liposarcoma. Hemangiosarcoma is a malignant,
Leiomyosarcoma is a malignant tumor relatively rare tumor of vascular origin,

of smooth muscular tissue, with a more lodged in the skin, skeletal muscle and
frequent location in the uterus, gastro- liver. Microscopically, it consists of atyp-
intestinal tract and retroperitoneal space ical endothelial and pericyte cells - ma-
(Fig. 8–42). By frequency, it ranks 3rd in lignant hemangioendothelioma and ma-
the retroperitoneal tissue, preceded by lignant hemangiopericytoma. Malignant
malignant fibrous histiocytoma and li- hemangioendothelioma is considered
one of the most malignant tumors with
rapid growth and multiple, abundant
and early metastases.
Lymphangiosarcoma (malignant
lymphangioendothelioma) appears due
to chronic lymphostasis after mastecto-
my. Histologically, it consists of fissured
lymphatic vessels, lined with atypical
and polymorphous endothelial cells; it
resembles the hemangioendothelioma.
Chondrosarcoma is a malignant tu-
Fig. 8–42. Leiomyosarcoma (hematoxylin–eo- mor of cartilaginous tissue, originating
sin stain; ×70).

Chapter 8 TUMORS
in the precursor cells of chondrocytes; the bone tissue and derives from plurip-
it is found more frequently in the long otent precursor cells of osteocytes. Most
limb bones (femur and humerus upper frequently, it is located in the femur, hu-
end), ribs, scapula, pelvic bones, vertebral merus (Fig. 8–44), tibia, pelvic and scap-
column (Fig. 8–43). It may be located in ular bones. Microscopically, atypical and
the medullary or periosteum area, in the polymorphic tumor cells are observed.
bones. It is characterized by slow growth The cells secrete various cytokines and
and late metastases. growth factors, which stimulate the
Osteosarcoma (osteogenic sarcoma) is proliferation of osteoblasts (osteoblastic
the most frequent malignant tumor of osteosarcoma), osteoclasts (osteolytic os-
Fig. 8–43. Chondrosarcoma– macroscopic as- Fig. 8–44. Osteosarcoma– macroscopic aspect.
pect..
teosarcoma) or capillaries (teleangiectatic early metastases.
osteosarcoma). Malignant mesothelioma is ob-
Malignant synovioma (synovial sar- served in the peritoneum, pleura and
coma) is found in large joints, but can pericardium. It tends to early expand
develop extraarticularly, in soft tissues and disseminate through lymphatic ves-
and retroperitoneal space. It can have sels; “tumor lymphangitis” develops and
monophasic or biphasic histological leads to appearance of multiple nodules
structure and be composed of gland-like on the serous membrane surface. Often,
epithelioid structures, in cells where cy- the tumor infiltrates the underlying tis-
tokeratin, a marker of epithelium, and sues. Typical metastases appear in re-
atypical cells resembling fibroblasts, are gional lymph nodes.
determined. It has a rapid growth and
8.5. TUMORS OF MELANIN-FORMING TISSUES
The melanocytes of neuroectoder- nant melanomas may develop from me-
mal origin are the development source lanocytes. The melanocytic cells express
of these tumors. They are localized in S–100 and HMB–45 antigens. Their
the basal layer of the epidermis, hair fol- immunohistochemical identification in
licles, most mucous membranes, covered tumor cells allows the correct diagnosis.
with stratified squamous epithelium, Pigmented nevi are benign tumors
leptomeniges, retina, vascular membrane that are most frequently met on the skin
of the eye. Pigmented nevi and malig- of the face and trunk. Histologically, they

TUMORS Chapte r 8
are agglomerations of melanocytic cells, prominent brown spot or plaque, with
called nevus cells or nevocytes (cells that smooth surface and hairless, several mil-
derive from Schwann cells of cutaneous limeters in diameter. Microscopically, it
nerves and can synthesize melanin). The consists of nests of nevus cells, located
nevus cell groups can be located at the at the level of dermo-epidermal junc-
level of dermo–epidermic junction, intra- tion, especially at the top of epithelial
dermally or an association of junctional ridges (Fig. 8–45 a, b). The basal layer
and intradermic locations. The following of the epidermis has a normal structure
varieties of nevi are distinguished: and may contain a greater number of
1) junctional nevus – macroscop- melanocytes. The junctional nevi, lo-
ically, it has the aspect of a slightly cated on the palms, soles and mucous
a b
Fig. 8–45 a, b. Junctional nevus: a – macroscopic aspect, b – microscopic pattern (hematoxylin–

eosin stain; ×70).
membranes have a high malignancy po- cells and nests of nevocytes lodged deep-

tential. ly in the dermis; it is rich in melanin.
2) dermal nevus – the most com-
monly met, especially on the head,
neck, trunk. Macroscopically, it has the
form of brown–black warts, with a ses-
sile or pedunculated base, smooth or
rough surface, often covered with hair,
down to a few mm size. Microscopical-
ly, it is formed from nests and cords of
nevus cells located only in dermis, usu-
ally, in the upper areas of the dermis,
around the pilosebaceous elements,
without being in contact with the epi- Fig. 8–46. Dermal nevus (hematoxylin–eosin
dermis (Fig. 8–46). Nevocytes contain stain; ×70).
a lot of melanin, giant multinucleated
cells are met. 4) juvenile or epithelioid cellular
3) compound or mixed nevus com- nevus is composed of epithelioid and
bines features of junctional and dermal fusiform cells with little melanin; giant
nevus and is formed of junctional nevus multinucleated cells of Langhans or Tou-

Chapter 8 TUMORS
ton type may be found. It lodges both at appear usually during puberty, pregnan-
the level of dermo-epidermal junction cy, and later, their growth becomes slow-
and in the dermis, more frequently in the er. Congenital nevocellular nevi rarely
face and leg area, being observed mainly become malignant, but the acquired
in children and adolescents. ones can turn into malignant mela-
5) blue nevus is composed of pro- nomas. Various factors of local chron-
liferating melanocytes, deeply lodged in ic irritation, such as repeated trauma,
the thickness of the dermis, at the level present favorable conditions for trans-
of reticular layer; it may invade the sub- formation into malignant melanoma.
cutaneous adipose tissue. It is met more Malignant melanoma or melanoblas-
frequently in the extremities and buttock toma is a highly malignant tumor, very
region. At macroscopic examination, it severe prognosis and propensity to he-
has the aspect of a 10–15 mm nodule of matogenous and lymphogenous metas-
dark blue color (Fig. 8–47). tasis. A more common location is the
skin of the face, extremities and external
genitalia. It constitutes 1,2% of malig-
nant tumors and 4% of all skin tumors.
As extracutaneous locations, the impair-
ment of eyeball (retina and choroid),
meningeal membranes and adrenal
medullary layer can be observed, more
rarely – the oral cavity and gastrointesti-
nal mucosa etc. It is seen more frequently
in women aged 30–50 years, on the skin,
legs, head and neck. The melanoma is
Fig. 8–47. Blue nevus– macroscopic aspect.. associated with chronic, solar radiation
Generally, pigmented nevi are con- (UV), which plays an important role in
sidered congenital or acquired skin ham- the tumor development. It frequently

artomas (hamartoma – pseudo-tumoral develops de novo, but, sometimes, it ap-
formation, composed of cells and tissues, pears through malignization of pre–ex-
normal components of the given organ). isting nevi. Macroscopically, on the skin,
Congenital nevi are observed on average it has the aspect of a spot, plaque (Fig.
in 1% of the newborn, the acquired ones 8–48 a) or a brown–black nodule with
a b
Fig. 8–48 a, b. Malignant melanoma with superficial extension: a – macroscopic aspect, b – micro-
scopic pattern (hematoxylin–eosin stain; ×70).

TUMORS Chapte r 8
a tendency to ulceration (Fig. 8–49 a); version – in the thickness of the dermis
there are cases of amelanotic melanoma (Fig. 8–49 b).
(non-pigmented). The most common The tumor cells are very diverse,
clinical morphological forms are the polymorphous, with epithelioid or fu-
forms with superficial and nodular ex- siform aspect, voluminous, hyperchro-
tension. Microscopically, in the first ver- mic nuclei, multiple mitoses, including
sion, the tumor consists of proliferating atypical ones, well–defined eosinophilic
atypical melanocytes, which form nests nucleoli, melanin granules in the cyto-
and cords along the dermo–epidermal plasm. Necrosis, hemorrhage and cal-
junction or in the basal layer of the epi- cification foci are observed in tumor.
dermis (Fig. 8–48 b), and, in the second The destructive lesions in melanoma

a b
Fig. 8–49 a, b. Malignant melanoma, nodular form: a – macroscopic aspect, b – microscopic pat-
tern (hematoxylin–eosin stain; ×70).
may lead to higher levels of melanin in IV – invasion of the reticular layer of

the blood and urine – melanemia and the dermis;
melanuria. The prognosis depends on V – invasion of subcutaneous adipose
the level of tumor invasion in the depth, tissue (of the hypodermis).
vertically. According to Klark, the fol- The 5–year survival prognosis of pa-
lowing levels of melanoma invasion are tients in I and II invasion levels is 100%,
distinguished: in III level - 88%, in IV level - 66% and
I – intraepidermal tumor (in situ); 15% - in V level. The prognosis also de-
II – invasion of dermis along hair fol- pends on tumor thickness.
licles; Melanoma develops early, multiple
III – damage of the whole papillary metastases by hematogenous and lym-
layer of the dermis up to the retic- phogenous ways. Melanin is contained
ular layer; in metastases.

Chapter 8 TUMORS
ESSENTIAL TERMS
on the subject “MESENCHYMAL TUMORS”
benign chondroblastoma hemangiopericytoma malignant myoblastoma

benign osteoblastoma hemangiosarcoma melanoma
blue nevus hibernoma mesothelioma
chondroma histiocytoma myoblastoma
chondrosarcoma junctional nevus myxoma
compound (mixed) nevus juvenile nevus myxosarcoma
dermal nevus leiomyoma nevus
dermatofibroma leiomyosarcoma osteoid osteoma
desmoid lymphangioma osteoma
elastofibroma lymphangiosarcoma osteosarcoma
fibroma lipoma rhabdomyoma
fibrosarcoma liposarcoma rhabdomyosarcoma
glomangioma malignant hibernoma sarcoma
hemangioendothelioma malignant histiocytoma synovial sarcoma
hemangioma malignant mesothelioma synovioma
TESTS
on the subject “MESENCHYMAL TUMORS”
SET I.
Multiple-choice questions with one cor- b) liver;

rect answer c) lungs;

1. What growth variant is characteristic for d) kidneys;
benign mesenchymal tumors: e) brain.
a) invasive; 4. All the listed signs characterize the uterine
b) infiltrative; leiomyoma, with the exception of:
c) destructive; a) collagen stroma is well-developed
d) by implantation; in many cases;
e) expansive. b) fascicles of smooth muscular cells
2. Which stain is used to differentiate fibroma are arranged chaotically;
from leiomyoma: c) tumor cells are homogenous in
a) carmine; form and structure;
b) toluidine blue; d) mitotic activity is high;
c) Congo red; e) muscular cells have oval nuclei.
d) picrofuchsin; 5. All the statements, regarding hematogeno-
e) thioflavin. us metastases, are correct, except for:
3. What is the location of the first hematogenic a) they are a consequence of
metastases of femur sarcoma: invasive growth of tumors;
a) lymph nodes;

TUMORS Chapte r 8
b) they are a consequence of tissue d) they are a criterion of malignant
embolism; tumor evolution;
c) they are characteristic for sarco- e) they are a manifestation of benign
mas; tumor growth.
SET II.
Multiple-choice questions with 2, 3 or a) lipoblastic lipoma;
more correct answers b) liposarcoma;
1.What signs from those listed bellow charac- c) infiltrative lipoma;
terize the benign mesenchymal tumor: d) malignant hibernoma;
a) tumors grow expansively, compre- e) malignant histiocytoma.
ssing neighboring tissues; 4. Which of the listed signs characterize the
b) tumor cells are mature, differenti- leiomyoma:
ated; a) it is the most frequent benign tu-
c) multiple typical and atypical mi- mor of the uterus;
toses are observed; b) tissular atypism;
d) metastasize limphogenously; c) multiple pathological mitoses;
e) as a rule, it does not recur after tu- d) it is frequently multicentric;
mor removal. e) tumor nodules are well-defined.
2. Which statements related to sarcoma are 5. Which of the listed signs characterize liver
correct: cavernous hemangioma:
a) the tumor is well-defined and a) tissular atypism;
compresses the neighboring tissu- b) it has the form of a well-defined
es; nodule;

b) it is brown or black on section; c) it is constituted from large vascu-
c) tumor cells are immature, atypical; lar cavities, filled with blood;
d) tumor cells infiltrate the adjacent d) it is constituted from capillary-
tissues; type vessels;
e) it may recur after tumor removal. e) expansive growth.
3. Which of the listed malignant tumors de-
rive from adipose tissue:
SET III.
The classification tests inclu- b) the tumor does not recur, as a rule;
de 2–4 subjects and a series of c) polymorphism and marked cellu-
answers. Indicate which answers lar atypism;
are correct for each separate subject. d) infiltrative tumor growth;
1. Which of the listed signs are characteristic e) tumor cells are mature, differenti-
for: ated;
I – benign mesenchymal tumors; f ) hematogenous metastases of tu-
II – malignant mesenchymal tumors; mors is typical;
a) relapse after tumor removal; g) compression and atrophy of adja-
cent tissues.

Chapter 8 TUMORS
2. What morphologic manifestations of me- b) it metastasizes more frequently by

senchymal tumors characterize: lymphogenous way;
I – tissular atypism; c) it metastasizes more frequently by
II – cellular atypism; hematogenous way;
a) presence of pathologic mitoses; d) it derives from epithelial tissues;
b) chaotic arrangement of structural e) the first metastases are observed in
elements in the tumor; regional lymph nodes;
c) tumor cells are mature, differenti- f ) the first metastases are observed in
ated; lungs and liver;
d) ratio between tumor stroma and g) on section, it has the aspect of fish
parenchyma is modified; meat.
e) tumor cells differ significantly 5. Which of the listed statements are correct
from original tissue cells; for:
3. Which of the listed morphological processes I – desmoid;
characterize: II – fibrosarcoma;
I – tumor expansive growth; a) it is formed from mature con-
II – invasive growth; nective tissue, with infiltrative
a) tumor cells invade the adjacent growth;
tissues; b) it is formed from immature,
b) the tumor does not have clear li- non-differentiated connective tis-
mits; sue;
c) the tumor nodule can be easily re- c) it does not develop metastases;
moved; d) it is lodged more frequently in the
d) tumor cells destroy blood and anterior abdominal wall;
lymph vessel walls; e) it metastasizes hematogenously;
e) usually, the tumor has the form of f ) numerous typical and atypical
a well-defined nodule. mitoses are observed in the tumor

4. Which of the listed statements refer to: nodule;
I – cancer (carcinoma); g) it is met more frequently in wo-
II – sarcoma; men.
a) it derives from mesenchymal tis-
sues;
Daily practice cases are presented with mobile, well-defined and dense. The micro-
clinical and morphological data from clini- scopic examination revealed that the tumor
cal histories and/or from necropsy protocols. was formed from fascicles of collagen fibers,
Each subject includes simple or multiple - arranged chaotically, and an insignificant
answer questions, with 1, 2 or more correct number of fibroblasts cells.
answers. Question:
1. A tumor nodule of 1,5 cm in diameter was What kind of tumor is in this case:
detected and removed from the forearm of
an 18-year-old patient. The nodule was a) leiomyoma;

TUMORS Chapte r 8
b) lipoma; 4. A tumor formation in the anterior abdomi-
c) melanoma; nal wall, without precise limits, appeared
d) hemangioma; in a 34-year-old patient, postpartum. The
e) hard fibroma. histological examination revealed that the
formation consists of fascicles of fibroblastic-
2. A red-colored nodule, which became pale
type cells, without signs of atypism; tumor
when pressed with a blade, appeared in the
cells infiltrate the adjacent muscular tissue.
cervical area of a 2-year-old child.
Question:
Question:
What is the presumptive diagnosis in this
What kind of tumor can be suspected in
case:
this case:
a) leiomyoma;
a) pigmented nevus;
b) mixed nevus;
b) intradermal nevus;
c) histiocytoma;
c) leiomyoma;
d) desmoid;
d) capillary hemangioma;
e) fibroma.
e) lymphangioma.
5. In a 12-year-old child, a tumor formati-
3. A well-delimited, whitish-colored (on sec- on without precise limits appeared in the
tion) tumor nodule of 2,0 cm in diameter epiphysis of the humeral bone, due to an
was found in the small intestine wall. The elbow contusion trauma. The histological
microscopic examination showed that it examination of biopsy revealed a large
was formed from fascicles of smooth muscu- number of osteoblastic-type polymorph cells,
lar fibers, with signs of tissue atypism. with a large number of pathologic mitoses.
Question: Question:
The presumptive diagnosis of which tumor What is the presumptive diagnosis in this
from those listed below can be establi- case:

shed in this case: a) chondrosarcoma;
a) fibroma; b) osteosarcoma;
b) lipoma; c) melanoma;
c) hemangioma; d) fibrosarcoma;
d) leiomyoma; e) synovial sarcoma.
e) desmoid.

ANSWERS TO THE TESTS
C H A P T E R 2. R E V E R S I B L E C E L LU L A R A N D E X T R AC E L LU L A R L E S I O N S
REVERSIBLE CELLULAR AND EXTRACELLULAR LESIONS

Set I Set II Set III Situational problems
1c 1 a, c, d 1 – I a, d; II b, c 1 – Ac; B 1b, 2a
2e 2 a, b, e 2 – I b, d, e; II a, c 2–cd
3b 3 b, d, f 3 – I a, b, c, d, e; II f 3 – A b; B b
4b 4 b, d 4 – I a, e, f, g; II b, c, d 4–e
5b 5 a, c, d, e 5 – I a, d, e, f; II b, c 5–e
MIXED EXTRA AND INTRACELLULAR LESIONS (MIXED DYSTROPHIES)

1c 1 a, c, d 1 – I b, d, e; II a, c, f 1 – a, c, e
2b 2 b, c, d 2 – I b, c, e, g; II a, d, f 2-d
3d 3 a, e 3 – I b, e, f; II a, c, d 3 – A b; B b
4c 4 c, d, e, f 4 – I a, c; II b, d 4 – A a; B a, b, d
5c 5 b, c, d, 5 – I a, b, c, d; II e 5 – A a, b, d, e; B b
CHAPTER3. IRREVERSIBLE CELLULAR LESIONS. NECROSIS AND APOPTOSIS

Set I Set II Set III Situational
problems
1d 1 a, c, d 1 – I c, d, f, h; II a, b, e, g 1 – b
2d 2 a, b, e 2 – I a, b, c, e, f; II d, g 2–a
3b 3 a, b, d, e 3 – I a, b, e, f; II c, d 3–d
4e 4 b, c, e 4 – I b; II e; III f; IV d; V 4 – d
a; VI c
5b 5 c, d 5 – I c, d, e, f, g, j; II a, 5–a
b, h, i

CHAPTER 4. DISTURBANCES OF BLOOD AND LYMPHATIC CIRCUL ATION
HYPEREMIA, DISORDERS, ISCHEMIA, INFARCTION, HEMORRHAGE

1e 1 b, c, f 1 – I b, e; II a, c, d, f, g 1 – A b, c; B c
2a 2 a, d, e, g 2 – I a, b, d, g; II c, e, f, h 2 – A a; Bb; C d
3c 3 a, b, e 3 – I b, c, d, e; II a 3 – Ad; B d
4c 4 a, b, c, d 4 – I a, e; II d, f; III b, c 4 – A e; B c
5e 5 b, e, f 5 – a, d; II b, c, e 5–Ab
THROMBOSIS, EMBOLISM, EDEMA, SHOCK

1 – I a; II b, c, d, e, f; III a;
1a 1 a, d 1 – A b; B c
IV f
2c 2 b, c, d 2 – I a, b, d, f; II c, e 2 – A e; B c; C b
3b 3 a, d 3 – I a, b, e; II c, f; III d 3 – A a; B c; C d, e
4 – I c, e, f, g; II a; III d; IV
4b 4 a, b, c, e 4 – Ad; B d
b
5c 5b 5 – I b, d, e; II a, c, f 5 – Ac; B a, d, f; C d
CHAPTER 5. INFL AMMATION
ACUTE (EXUDATIVE) INFLAMMATION

1d 1 b, d, e 1 – I a, e, f; II b, c, d 1-c
2c 2 a, d 2 – I a, c, d; II b, e, f, g 2-a
3d 3 b, d 3 – I c, f, g; II a, b, d, e 3 – Ac; B c; C b
4c 4 d, e 4 – I a, c, d; II b, e 4 – Ad; B b, c, d, e
5c 5 a, d, e 5 – I b, d, f, h; II a, c, e, g 5 – A e; B c
CHRONIC INFLAMMATION (PROLIFERATIVE)
1c 1 a, b, c 1 – I b, e, f, h; II a, c, d, g 1 – A e; B a; C b, c, e
2b 2 b, c, d 2 – I b, c; II a, d, e, f 2–c
3a 3 c, d, e 3 – b, c; II a, d, e 3–c
4d 4 a, b, e 4 – I a, c, e, f; II b, d, g 4–c
5d 5 a, b, e 5 – I b; II c; III a; IV e; V d 5–c

CHAPTER 6. IMMUNOPATHOLOGIC PROCESSES

1e 1 a, b 1 – I b, d, e; II a, c, f 1 – Ad; Bb
2b 2 b, c, e 2 – I a, c, e; II b, d 2 – Ad; Bb
3c 3 b, d, e 3 – I c, d; II a, b, e 3 – Ab; Bd
4d 4 b, c, e 4 – I b; II d; III c; IV a 4 – Ad; Bd
5d 5 b, d 5 – I b; II a, c, d, e 5 – Ad; B c, e
CHAPTER 7. ADAPTIVE– COMPENSATORY PROCESSES

1e 1 b, d, e 1 – I b, d, e; II a, c 1 – Ac; Bb
2d 2 b, c, d, e 2 – I b, d, e; II a, c 2 – A a, e; B a, b, c, d
3c 3 d, e 3 – I d, e; II a, b, f; III c 3–b
4e 4 a, c, e 4 – I b, c, d; II a, e 4–d
5a 5 a, b, c, d 5 – I b, e; II a, c, d 5 – A e; B d
CHAPTER 8. TUMORS
NON ORGAN-SPECIFIC EPITHELIAL TUMORS

1a 1 b, c 1 – I b, d, g; II a, c, e, f 1–b
2d 2 a, d 2 – I b, c, d; II a, e, f 2 – a, b, c, e
3e 3 a, d 3 – I c, e, f; II a, b, d 3–d
4e 4 b, c 4 – I b, d, e, g; II a, c, f 4–a
5b 5 b, c, e 5 – I c, d, h; II a, b, e, f, g 5–d
MESENCHYMAL TUMORS
1e 1 a, b, e 1 – I b, d, g; II a, c, e, f 1–e
2d 2 c, d, e 2 – I b, c, d; II a, e 2–d
3c 3 a, b, c, d 3 – I c, e; II a, b, d 3–d
4d 4 a, b, d, e 4 – I b, d, e; II a, c, f, g 4–d
5e 5 a, b, c, e 5 – I a, c, d, g; II b, e, f 5–b

CON T E N TS
Bibliography
1. KUMAR V., ABBAS A. K., FAUSTO N., MITCHELL R. N.

Robbins Basic Pathology, 8-th ed.. Saunders Elsevier, 2007.
2. VATAMAN V., ZOTA Ie. Morfopatologie generală. Chis-
inău-București, 1997.
3. ZOTA Ie., VATAMAN V. Morfopatologie generală. Chisinau,
2010.
4. STRUKOV A., SEROV V. Anatomia patologică. Chisinău,
1999.
5. COOKE R. A., STEWART B. Colour atlas of anatomical pa-
thology, 3-rd ed.. Churchill Livingstone, 2004.
6. STEWART A., LOWE J. Pathology, second ed., Mosby, 2000.
7. DAMJANOV I. Pathology secrets, 3-rd ed. Mosby Elsevier,
2009.
8. CONSTANTINIDES P. Ultrastructural pathology. Amster-
dam-New York-Oxford, 1984.
9. HOLLMAN J. H. Pathology. Sprienger-Verlag, 1992.
10. CURRAN R. C. Colour atlas of histopathology. London,

1972.
11. PALITSEV M., ANICIKOV N. Patologhicescaia anatomia.,
vol.1, Moscva, 2001.

CO N TEN TS
CONTENTS
Introduction to morphopathology ............................................................................. 3

Chapter 1. Death of the body ...................................................................................... 7
Chapter 2. Cellular and extracellular reversible lesions ............................................. 10
2. 1. Causes of cellular/extracellular lesions .................................................................... 10
2. 2. Morphology of cellular and extracellular reversible lesions ...................................... 11
2. 3. Cellular lesions (parenchymatous cellular dystrophies) ............................................ 13
2. 3. 1. Proteic cellular dystrophies .................................................................... 14
2. 3. 2. Lipidic cellular dystrophies (cellular lipidoses) ......................................... 17
2. 3. 3. Glucidic cellular dystrophies .................................................................. 20
2. 4. Extracellular dystrophies (mesenchymal or stromal vascular) .................................. 22
2. 4. 1. Proteic extracellular dystrophies (extracellular disproteinoses) ................. 22
2. 4. 1. 1. Mucoid intumescence ......................................................................... 23
2. 4. 1. 2. Fibrinoid intumescence ...................................................................... 23
2. 4. 1. 3. Extracellular hyalinosis (hyaline dystrophy)........................................... 24
2. 4. 2. Lipidic extracellular dystrophies .............................................................. 26

2. 4. 3. Glucidic extracellular dystrophies............................................................. 27
2. 5. Accumulation diseases (thesaurismoses or storage diseases) ................................. 28
2. 5. 1. Hereditary disorders of amino acid metabolism ...................................... 28
2. 5. 2. The lysosomal accumulation diseases (lysosomal storage diseases) ............. 28
2. 5. 2. 1. Systemic lipidoses or lipidic storage diseases ........................................ 29
2. 5. 2. 2. Glycogenoses or glycogenic storage diseases ......................................... 29
2. 5. 2. 3. Mucopolysaccharidoses ...................................................................... 29
Essential terms on the subject “Reversible cellular and extracellular lesions”................... 30
Tests on the subject “Reversible extracellular and cellular lesions” .................................. 30
2. 6. Reversible mixed intra and extracellular lesions (mixed dystrophies)................... 33
2. 6. 1. Chromoproteins dystrophies .................................................................. 34
2. 6. 1. 1. Hemoglobinogenic pigment dystrophies .............................................. 34
2. 6. 1. 2. Dystrophies of proteinogenic pigments ............................................... 38
2. 6. 1. 3. Dystrophies of lipidogenic pigments .................................................... 41

CON T E N TS
2. 6. 2. Dystrophies of nucleoproteins................................................................. 42
2. 6. 3. Mineral dystrophies. Pathologic calcification ........................................... 43
2. 6. 4. Calculogenesis (lithiasis)....................................................................... 44
Essential terms on the subject “Mixed extra and intracellular lesions
(mixed dystrophies)” ................................................................................................. 45
Tests on the subject “Mixed extra and intracellular lesions (mixed dystrophies)”
(mixed injuries) ......................................................................................................... 46
Chapter 3. Irreversible cellular lesions. Necrosis and apoptosis ....................... 50

3. 1. Necrosis ........................................................................................................... 50
3.1. 1. Clinical and morphological forms of necrosis ....................................... 53
3. 1. 2. Effects and consequences of necrosis .................................................... 58
3. 2. Apoptosis......................................................................................................... 60
Essential terms on the subject “Irreversible cellular lesions. Necrosis and apoptosis” ........ 63
Tests on the subject “Irreversible cellular lesions. Necrosis and apoptosis” ...................... 63
Chapter 4. Disturbances of blood and lymphatic circulation ............................ 67

4.1. Hyperemia ...................................................................................................... 67
4. 1. 1. Arterial hyperemia.................................................................................. 67
4. 1. 2. Venous hyperemia (of stasis) ................................................................ 68
4. 1. 2. 1. Generalized venous hyperemia ......................................................... 68
4. 1. 2. 2. Localized venous hyperemia ............................................................. 72

4. 2. Ischemia ......................................................................................................... 72
4. 2. 1. Variants of ischemia.............................................................................. 72
4. 3. Infarction ................................................................................................. 73
4. 3. 1. Morphologic characteristics of infarctions of different organs.............. 75
4. 4. Hemorrhage .................................................................................................... 79
4. 4. 1. Mechanisms of hemorrhages................................................................. 79
4. 4. 2. Terminology of hemorrhages................................................................ 80
4. 4. 3. The most frequent consequences of internal hemorrhages .................... 82
4. 5. Plasmorrhagia.................................................................................................. 82
Essential terms on the subject “Disturbances of blood circulation: hyperemia,
ischemia, infarction, hemorrhage”................................................................................. 83
Tests on the subject “Disturbances of blood circulation: hyperemia, ischemia, infarction,
hemorrhage” ............................................................................................................. 83
4.6. Thrombosis ...................................................................................................... 87

CO N TEN TS
4. 6. 1. Thrombogenesis mechanisms ............................................................... 87
4. 6. 2. Morphogenetic stages of thrombosis ................................................... 89
4. 6. 3. Morphology of thrombi ...................................................................... 90
4. 7. Embolism ........................................................................................................ 93
4. 7. 1. Variants of embolism according to the composition ............................. 93
4. 7. 2. Variants of embolisms according to the direction of the embolus
spreading ......................................................................................................... 96
4. 7. 3. Consequences of embolism................................................................... 97
4. 8. Stasis (hemostasis) ......................................................................................... 98
4. 9. Shock ............................................................................................................. 98
4.10. Disseminated intravascular coagulation (DIC syndrome) ............................. 99
4. 11. Edema ........................................................................................................ 100
4. 11. 1. Pathogenetic mechanisms in development of edemas ...................... 100
4. 11. 2. Classification of edemas according to production mechanism .......... 101
4. 11. 3. Terminology of edemas..................................................................... 101
4. 12. Lymphatic circulation disturbances.............................................................. 102
Essential terms on the subject “Thrombosis, embolism, edema, shock” .......................... 103
Tests on the subject “Thrombosis, embolism, edema, shock” ......................................... 103
Chapter 5. Inflammation ................................................................................. 108
5.1. Causes, morphology, terminology and classification of inflammation............. 108

5. 2. Acute (exudative) inflammation .................................................................... 115

5. 2. 1. Serous inflammation........................................................................... 115
5. 2. 2. Fibrinous inflammation....................................................................... 116
5. 2. 3. Purulent inflammation........................................................................ 119
5. 2. 4. Putrid inflammation (ichorous or gangrenous)................................... 122
5. 2. 5. Hemorrhagic inflammation................................................................. 122
5. 2. 6. Catarrhal inflammation....................................................................... 122
5. 2. 7. Mixed inflammation .......................................................................... 123
Essential terms on the subject “Acute (exudative) inflammation” ................................. 123
Tests on the subject “Acute (exudative) inflammation” ............................................... 123
5. 3. Chronic (proliferative, productive) inflammation .......................................... 127
5. 3. 1. Interstitial inflammation .................................................................... 127
5. 3. 2. Granulomatous inflammation ............................................................ 129
5. 3. 2. 1. Specific granulomatous inflammations ........................................... 130

CON T E N TS
5. 3. 2. 2. Tuberculous granulomatous inflammation ...................................... 130
5. 3. 2. 3. Syphilitic (luetic) granulomatous inflammation ............................. 131
5. 3. 2. 4. Leprous granulomatous inflammation ............................................ 133
5. 3. 2. 5. Granulomatous inflammation in rhinoscleroma ............................ 133
5. 3. 2. 6. Productive inflammation with polyp formation ............................. 136
Essential terms on the subject “Chronic (proliferative, productive) inflammation” ....... 136
Tests on the subject “Chronic (proliferative, productive) inflammation” ....................... 136
Chapter 6. Immunopathologic processes ..................................................... 140

6. 1. Lesions of the thymus ................................................................................... 143
6. 2. Hypersensitivity reactions ............................................................................ 144
6. 3. Autoimmune diseases ................................................................................... 149
6. 4. Immunodeficiency syndromes ....................................................................... 155
Essential terms on the subject “Immunopathological processes” ................................... 157
Tests on the subject “Immunopathological processes” ................................................... 157
Chapter 7. Adaptive–compensatory processes ............................................ 161

7. 1. Adaptive processes ....................................................................................... 161
7. 1. 1. Atrophy............................................................................................... 161
7. 1. 2. Adaptive hypertrophy (hyperplasia) ................................................. 163
7. 1. 3. Organization and encapsulation ........................................................ 164

7. 1. 4. Morphological restructuration of tissues ............................................ 165
7. 1. 5. Metaplasia........................................................................................... 165
7. 1. 6. Dysplasia ............................................................................................ 166
7. 2. Compensatory processes ............................................................................... 167
7. 2. 1. Regeneration ..................................................................................... 167
7. 2. 1. 1. Varieties of regeneration ................................................................ 167
7. 2. 1. 2. Regeneration of different tissues and organs ............................... 169
7. 2. 2. Hypertrophy and hyperplasia ............................................................ 176
7. 3. Wound healing .............................................................................................. 178
Essential terms on the subject “Adaptive–compensatory processes”................................ 181
Tests on the subject “Adaptive–compensatory processes” ............................................... 181
Chapter 8. Tumors ............................................................................................ 186

8. 1. Etiology and pathogenesis of tumors ........................................................... 186
8. 2. 1. Macroscopic characteristics of tumors .............................................. 186

CO N TEN TS
8. 1. 2. Theory of physical carcinogenesis ....................................................... 187
8. 1. 3. Theory of viral carcinogenesis ............................................................ 188
8. 1. 4. Proto–oncogenes and cellular oncogenes ............................................ 189
8. 2. Structure of tumors ........................................................................................ 191
8.2.1. Macroscopic characteristics of tumors................................................................ 191
8. 2. 2. Microscopic aspect of tumors...................................................................... 192
8. 2. 3. Metastasis and relapse of tumors .............................................................. 193
8. 2. 4. Morphogenesis of tumors............................................................................ 195
8. 2. 5. Growth of tumors................................................................................195
8. 2. 6. Classification of tumors .............................................................................. 196
8. 2. 7. General and local complications of tumors .............................................. 199
8. 3. Epithelial tumors with no specific location (non organ-specific) .................... 200
8. 3. 1. Benign epithelial tumors ............................................................................ 200
8. 3. 2. Malignant epithelial tumors ...................................................................... 202
Essential terms on the subject “Non organ-specific epithelial tumors” ............................ 207
Tests on the subject “Non organ-specific epithelial tumors” ........................................... 207
8. 4. Mesenchymal tumors ..................................................................................... 211

8. 4. 1. Benign mesenchymal tumors...................................................................... 212
8. 4. 2. Malignant mesenchymal tumors ................................................................ 217
8. 5. Tumors of melanin–forming tissues .............................................................. 220
Essential terms on the subject “Mesenchymal tumors” .................................................. 224

Tests on the subject “Mesenchymal tumors” .................................................................. 224
Answers to the tests ............................................................................................ 228
Bibliography........................................................................................................ 231


Zota, Vataman. General Morphopathology. 2014

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Zota, Vataman. General Morphopathology. 2014

Uploaded by

Copyright:

Available Formats

Ministry of Health of the Republic of Moldova

State University of Medicine and Pharmacy

IEREMIA ZOTA, VLADIMIR VATAMAN

C entrul E ditorial -P oligrafic M edicina

Zota_Morfopatologia eng_2014red.indd 1 8/19/14 16:24

Ieremia ZOTA – Professor, Department of Morphopathology, State Medical and

General morphopatology / Ieremia Zota, Vladimir Vataman,

© Design & Prepress: Veaceslav Popovschi

© CEP Medicina, 2014

Zota_Morfopatologia eng_2014red.indd 2 8/19/14 16:24

3  G E N E R A L M O R P H O P A T O L O G Y IEREMIA ZOTA, VLADIMIR VATAMAN

Zota_Morfopatologia eng_2014red.indd 3 8/19/14 16:25

influence the therapeutic ap- completely, with the intact sur-

ination. At present, a biopsy sample can dometrium, cervical canal, buccal

Zota_Morfopatologia eng_2014red.indd 4 8/19/14 16:25

5  G E N E R A L M O R P H O P A T O L O G Y IEREMIA ZOTA, VLADIMIR VATAMAN

EXAMINATION OF POSTOPERATIVE PIECES

According to the current require- scopic description of postoperative pie-

Zota_Morfopatologia eng_2014red.indd 5 8/19/14 16:25

in tumor pathologies, as well as to esti- stained by different methods. The speci-

POSTMORTEM EXAMINATION (NECROPSY)

NECROPSY (from the Greek ne- confrontation results of the anatomo-

physician, whose presence is obligatory modelling of some diseases on animals

Zota_Morfopatologia eng_2014red.indd 6 8/19/14 16:25

DEATH OF THE BODY

7  G E N E R A L M O R P H O P A T O L O G Y IEREMIA ZOTA, VLADIMIR VATAMAN

Zota_Morfopatologia eng_2014red.indd 7 8/19/14 16:25

Zota_Morfopatologia eng_2014red.indd 8 8/19/14 16:25

9  G E N E R A L M O R P H O P A T O L O G Y IEREMIA ZOTA, VLADIMIR VATAMAN

Zota_Morfopatologia eng_2014red.indd 9 8/19/14 16:25

CELLULAR AND EXTRACELLULAR

meostasis), which ensures the survival  irreversible lesions;

Zota_Morfopatologia eng_2014red.indd 10 8/19/14 16:25

1 1  G E N E R A L M O R P H O P A T O L O G Y IEREMIA ZOTA, VLADIMIR VATAMAN

2.2 MORPHOLOGY OF CELLULAR

Zota_Morfopatologia eng_2014red.indd 11 8/19/14 16:25

cellular metabolic disturbances. By pro- stances which are encountered in

the myocardial ischemia can be tracked or in the extracellular compartment.

Zota_Morfopatologia eng_2014red.indd 12 8/19/14 16:25

Varieties of dystrophies according

1 3  G E N E R A L M O R P H O P A T O L O G Y IEREMIA ZOTA, VLADIMIR VATAMAN

Classification of cellular dystrophies

ØØ fatty cellular dystrophy (steatosis)

Zota_Morfopatologia eng_2014red.indd 13 8/19/14 16:25

2.3.1. PROTEIC CELLULAR DYSTROPHIES

Granular dystrophy (cloudy intu- (for example: appearance of proteinuria

teic masses and an insignificant tume- Cellular hyaline dystrophy (in-

Zota_Morfopatologia eng_2014red.indd 14 8/19/14 16:25

1 5  G E N E R A L M O R P H O P A T O L O G Y IEREMIA ZOTA, VLADIMIR VATAMAN

Zota_Morfopatologia eng_2014red.indd 15 8/19/14 16:25

glycogen and lipids (the absence of stai-

chondria (Fig. 2–5). A certain diagnosis squamous epithelium (hyperkeratosis)

Zota_Morfopatologia eng_2014red.indd 16 8/19/14 16:25

Fig. 2-7. Leucoplazia mucoasei bucale.

Fig. 2–7. Leukoplakia of buccal mucosa.

layer is formed from keratinized, enu-

1 7  G E N E R A L M O R P H O P A T O L O G Y IEREMIA ZOTA, VLADIMIR VATAMAN

Zota_Morfopatologia eng_2014red.indd 17 8/19/14 16:25

The following methods of staining by the inhomogeneous character of the

Fig. 2–8 a, b, c. Fatty dystrophy of myocardium

Zota_Morfopatologia eng_2014red.indd 18 8/19/14 16:25

1 9  G E N E R A L M O R P H O P A T O L O G Y IEREMIA ZOTA, VLADIMIR VATAMAN

Zota_Morfopatologia eng_2014red.indd 19 8/19/14 16:25