Systemic Patan

MINISTRY OF EDUCATION AND SCIENCE OF THE RUSSIAN
FEDERATION
S.I. Georgievsky Medical Academy
Federal State Autonomous Educational Institution of Higher

Education
"Crimean Federal University named after B.I. Vernadsky". B.I.
Vernadsky"
SHORT COURSE IN PATHOMORPHOLOGY

PART II: PRIVATE PATHOLOGY
educational and methodological manual for students of higher educational

medical institutions
Simferopol, 2018
2
UDC 616-091 (072)
BBK 52.5
Authors: Kriventsov M.A., Filonenko T.G., Shalanin B.B., Davydova A.A., Golubinskaya
E.P., Ermola Yu.
Reviewers:
Kubyshkin Anatoly Vladimirovich, Professor, Doctor of Medical Sciences, Head of

the Department of General and Clinical Pathophysiology of the S.H. Kubyshkin Medical
Academy. C.H. Kubyshkin Anatoly Vladimirovich, Professor, Doctor of Medical Sciences,
Head of the Department of General and Clinical Pathophysiology of the C.H. Feorgievsky
Medical Academy (structural subdivision) of V.H. Vernadsky Federal Federal Autonomous
Educational Institution of Higher Professional Education. Vernadsky".
Antonina Budnik, Candidate of Medical Sciences, Associate Professor, Department

of Normal and Pathological Anatomy, Kabardino-Balkarian State University named after
X.M. Berbekov. X.M. Berbekov Kabardino-Balkarian State University.
A short course in pathomorphology. Part II: private pathology. Textbook for students of
higher educational medical institutions / Kriventsov M.A., Filonenko T.G., Shalanin B.B.,
Davydova A.A., Golubinskaya E.P., Ermola Y.A. - Simferopol, 2018. - 317 pp.
The textbook on pathological anatomy was prepared at the Department of

Pathological Anatomy with a sectional course of the S. I. Georgievsky Medical Academy
(structural subdivision) of the Crimean Federal University named after B. I. Vernadsky. B.I.
Vernadsky". B educational and methodical manual outlines the basic information on the
issues of private pathology in accordance with the current working program for the
discipline of "Pathological Anatomy", according to the educational standard FSES3+. The
advantage of this textbook for students is the brevity and structure of the material presented
with a large number of explanatory figures, tables and diagrams. The presented material is
sufficient for full assimilation of knowledge on the discipline "Pathological anatomy" in the
framework of its teaching for students of higher medical educational institutions of III-IV
level of accreditation.
Authors: staff of the Department of Pathological Anatomy with a sectional course of
the S.I. Georgievsky Medical Academy (structural subdivision) of the Crimean Federal
University named after B.I. Vernadsky (Head of the Department - Associate Professor, Dr.
M.A. Kriventsov). B.I. Vernadsky" (Head of the Department - Associate Professor, Dr.
M.A. Kriventsov).
The textbook is recommended for publication and assignment of the Academic

Council of the Academic Council of V.H. Vernadsky KFU. Vernadsky" (Minutes № 12 of
December 22, 2017).
© Kriventsov M.A., Filonenko T.G., Shalanin B.B., Davydova A.A., Golubinskaya E.P.,
Ermola Y.A.
3
DEDICATED TO THE TEACHER
DOCTOR OF MEDICAL SCIENCES, PROFESSOR

ALEXANDER KIMOVICH ZAGORULKO
4
SECTION I
CARDIOVASCULAR DISEASES
► ATHEROSCLEROSIS◄
Atherosclerosis (from Greek athere - porridge and sklerosis -

thickening) is a chronic disease resulting from a violation of fat
and protein metabolism, characterized by lesions of arteries of
elastic and elastic-muscular type in the form of focal deposition of
lipids and proteins in the intima and reactive overgrowth of
connective tissue.
ETHIOLOGY
There are 2 groups of etiologic factors:
• Factors contributing to atherogenic lipoproteins in the body:
-dysfunctions of the nervous and endocrine systems, liver, GI tract;
-hereditary predisposition.
• factors, having adverse impact on
the cleansing ability of the intima:
- intoxication;
- infections;
-immune factors;
- age;
-hemodynamic damaging factors;
- heredity;
-regenerative capacity of the endothelium.
PATHOGENESIS.
The pathogenesis of atherosclerosis is characterized by stages:
• Atherogenic dyslipoproteinemia with predominance of low-density
lipoproteins (LDL) and very low-density lipoproteins (VLDL);
• Lipoprotein accumulation in the intima of blood vessels;
• endothelial damage;
• increased vascular permeability;
• platelet and monocyte adhesion;
• migration and accumulation of macrophages in the intima with
their subsequent transformation into xanthoma (foamy) cells;
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• The appearance of lipid spots and streaks;

• migration of smooth muscle cells into the intima;
• plaque formation and transformation.
Figure 1. Scheme of pathogenesis of atherosclerosis.
PATHOLOGIC ANATOMY AND MORPHOGENESIS

The following microscopic stages of atherosclerosis morphogenesis are
distinguished:
1. dolipid;
2. lipoidosis;
3. liposclerosis;
4. atheromatosis;
5. ulceration;
6. atherocalcinosis.
Dolipid stage:
Macroscopically undetectable
- accumulation of acidic glycosaminoglycans in the intima,

mucoid swelling of the inner membrane;
- when using thiazine dyes (toluidine blue), metachromasia
is determined in areas of early disorganization of
connective tissue.
6
The lipoidosis stage is characterized by focal infiltration of the intima by

lipids (cholesterol), lipoproteins, leading to the formation of fatty (lipid)
spots and streaks.
Fatty spots appear as yellow-colored areas that can sometimes
merge to form flat, elongated bands that do not rise above the
surface
of the intima.
Lipids accumulate in smooth muscle cells and macrophages,

which are called foamy, or xanthoma, cells (from Greek
hanthos - yellow).
Lipid inclusions also appear in the endothelium, indicating
infiltration of the intima by blood plasma lipids. Swelling and
destruction of elastic membranes are observed. In these areas
when applying
dyes on fats (e.g. Sudan III or IV) reveal lipids.
The earliest appearance of fatty spots and streaks is in the aorta and its
branches, then in the large arteries. The appearance of such spots does not
mean the presence of atherosclerosis, because the appearance of lipid spots
can be observed in early childhood not only in the aorta, but also in the
coronary arteries of the heart. With age, lipid spots, the so-called
manifestations of "physiologic early lipidosis", in the vast majority of cases
disappear and are not a source of development of further atherosclerotic
changes. Similar changes in vessels in young people can be detected in some
infectious diseases.
Liposclerosis
Fibrotic plaques are dense, round or oval-shaped white or
yellowish-white formations rising above the surface of the
intima. These plaques narrow the lumen, which is accompanied
by impaired blood flow (ischemia) to the organ or its part.
Fibrous plaques are most often observed in the abdominal
aorta, in branches branching from the aorta, in the arteries of
the heart, brain, kidneys, lower limbs, carotid arteries, and in
the aorta.
arteries, etc.
Proliferation of fibroblasts, the growth of which stimulates the

destruction of xanthoma cells and the growth of granulation
tissue in the intima. Subsequent maturation of this
tissue is accompanied by the formation of fibrous plaque.
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Application special dyes allows в

in the fibrous plaques to detect lipids.
Atheromatosis
Dense plaques of rounded shape, elevated above the intima
surface with crumbling detritus in the
center.
An atheromatous plaque consists of a fibrous covering

(constructed of smooth muscle cells and extracellular matrix),
and a necrotic "core" consisting of tissue detritus, extracellular
fat with cholesterol crystals and foam cells.
Progression of atheromatous changes leads to destruction of the plaque

cover. This period is characterized by a large number of various
complications.
Stage of ulceration
Atheromatous ulcer with undermined, irregular edges; its floor
is formed by the muscular and sometimes adventitial layer of
the vessel wall, thrombotic masses appear and
foci of hemorrhage.
The ulcerative intimal defect is often covered by thrombotic

masses. Hemorrhage into the plaque thickness (intramural
hematoma) is possible.
As a result of necrosis of the deep layers of the vessel wall, an aneurysm
(bulging of the wall) may form. Often blood peels the intima from the
middle layer, and then there are dissecting aneurysms. The danger of these
complications lies in the possibility of rupture of either the aneurysm or the
vessel wall at the site of atheromatous ulcers. Atheromatous masses can be
washed out by blood flow and form emboli.
Atherocalcinosis
Plaques acquire stony density, the vessel wall in the
petrification site is sharply deformed, white in color.
Foci of calcifications in atheromatous masses, fibrous tissue, in

the interstitial substance between elastic fibers.
The development of the last two stages is optional, and are complications of
the disease.
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CLINICAL AND ANATOMICAL FORMS OF ATHEROSCLEROSIS

1. Atherosclerosis of cerebral vessels - the morphologic basis of
cerebrovascular disease.
• acute form - leads to the development of ischemic or hemorrhagic
infarction of the brain, clinically expressed as ischemic stroke;
• chronic form - leads to atrophy of the frontal gyrus, manifested in
dementia (encephalopathy).
2. Coronary artery atherosclerosis is the morphologic basis of coronary
heart disease.
• acute forms of coronary heart disease (CHD) are expressed in the
development of myocardial infarction or acute heart failure
without infarction as a result of narrowing of the coronary artery
lumen by 2\3 of the vessel lumen over 75%;
• chronic form of CHD is manifested by the development of diffuse
cardiosclerosis as a result of narrowing of the vessel lumen by 1\3.
In addition, atherosclerotic plaques may develop on the aortic
valve, leading to its thickening, deformation and shortening, i.e.
development of aortic valve insufficiency (acquired defect).
3. Atherosclerosis of the mesenteric arteries - mostly associated with
lesions of the abdominal aorta and the apertures of the mesenteric
arteries.
• acute form - manifested as a result of thrombosis with the
development of intestinal gangrene;
• chronic form - manifested as atrophy of the intestinal musculature
and sclerosis, clinically - intestinal atony and intestinal
obstruction.
4. Atherosclerosis of the arteries of the lower extremities.
• The acute form is gangrene of the foot;
• Chronic form - intermittent claudication, weakness in the legs,
trophic ulcers.
5. Aortic atherosclerosis - develops mainly in the mouths of outgoing
arteries, as a result of thrombosis, thromboembolism and embolism
with atheromatous masses in aortic atherosclerosis often observed
renal infarction and gangrene of the intestine, possible infarction of
the spleen, kidneys. In diffuse lesions of the aortic wall, the wall may
bulge at the site of its damage (aneurysm) with or without ulceration:
• differentiate cylindrical, sac-shaped, hernia-like
aneurysms. In some cases, the wall of the aneurysm is formed by the aorta
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- true aneurysm; in others, adjacent tissue and hematoma - false

aneurysm. If blood peels off the middle aortic sheath from the
intima or adventitia, an endothelium-covered channel is formed - a
delaminating aneurysm, which is dangerous for rupture and
bleeding. A long-lasting aortic aneurysm leads to atrophy of
surrounding tissues (e.g., sternum, vertebral bodies).
6. Atherosclerosis of renal arteries - leads to the development of either
wedge-shaped areas of parenchyma atrophy with collapse and stromal
sclerosis, or infarcts with subsequent formation of retracted scars.
There is a large atherosclerotic shriveled kidney (nephrosclerosis), the
function of which suffers little, as most of the parenchyma remains
intact. As a result of renal tissue ischemia in stenotic atherosclerosis of
renal arteries, symptomatic (renal) hypertension develops in some
cases.
COMPLICATIONS, OUTCOMES
Deformation with stenosis of arterial lumen leads to ischemia of organs. If it
develops quickly (with spasm, obturating thrombus), tissue necrosis occurs;
if it develops slowly (with gradual narrowing of the lumen), tissue atrophy
occurs.
Complications of atherosclerosis:
1. Acute complications - caused by the occurrence of thrombi, emboli,
vasospasm. There is an acute occlusion of vessels, accompanied by
acute vascular insufficiency (acute ischemia), leading to the
development of infarcts of organs (e.g., myocardial infarction, gray
softening of the brain, gangrene of the limb, etc.). Sometimes rupture
of the aneurysm of the vessel with a fatal outcome can be observed.
2. Chronic complications - atherosclerotic plaque protruding into the
vessel lumen leads to narrowing (stenosis) of its lumen (stenosing
atherosclerosis). Since the formation of plaque in vessels is a slow
process, there is chronic ischemia in the area of blood supply of the
vessel. Chronic vascular insufficiency is accompanied by hypoxia,
dystrophic and atrophic changes in the organ and connective tissue
overgrowth. Slow occlusion of vessels is accompanied by the
development of small-focal sclerosis in organs.
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► HYPERTENSION ◄
Hypertension (primary, or essential, idiopathic hypertension) is a

chronic disease, the main clinical sign of which is a prolonged
and persistent increase in blood pressure (hypertension).
There is currently no consensus on which blood pressure (BP) values
should be considered as manifestations of hypertension. However, most data
indicate that hypertension can be considered to be a prolonged persistence of
BP greater than 140/90 mmHg.
According to this, two main forms of hypertension are distinguished

by etiology:
1. Primary (essential) hypertension - the cause is unknown;
2. Secondary (symptomatic) hypertension, which is a manifestation
of other diseases:
• CNS diseases: encephalitis, poliomyelitis at the brain stem
level, brain tumors and traumas;
• endocrine system diseases: adrenal tumors (pheochromocytoma,
aldosteroma, corticosteroma), endocrine-sexual hypertension
(menopause in women and men);
• diseases of the kidneys and urinary tract (glomerulonephritis,
pyelonephritis, hydronephrosis, etc.);
• Vascular diseases (atherosclerosis of the aortic arch and
coarctation, systemic vasculitis, narrowing and anomalies of
arteries).
By the nature of the course of hypertension is divided into malignant

(malignant hypertension) and benign (benign hypertension). Malignant
hypertension is dominated by manifestations of hypertensive crisis, i.e. a
sharp increase in blood pressure (systolic and diastolic sometimes by 100
mm Hg from the initial level) as a result of spasm of arterioles.
Morphologic manifestations of hypertensive crisis
• corrugation and destruction of the basal membrane, endothelium
arrangement in the form of a frequentocolor as a result of arteriolar
spasm;
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• plasma saturation or fibrinoid necrosis of its wall;

• thrombosis, sludge phenomenon.
During hypertensive crisis, morphologic manifestations dominate in
any one organ, which determines the clinical specificity of the crisis. Thus,
renal arteriolonecrosis leads to acute renal failure, plasmatic impregnation of
arterioles and diapedesis hemorrhages in the floor of the IV ventricle - to
sudden death.
Currently, malignant hypertension is rare, with benign and slowly
progressive hypertension predominating.
In the benign form of hypertension, three stages with certain

morphologic differences are distinguished:
1. preclinical stage;
2. stage of pronounced widespread morphologic changes of arterioles
and arterioles;
3. stage of secondary changes of internal organs due to vascular changes
and violation of intraorgan circulation.
At the same time, at any stage of benign hypertension, a hypertensive
crisis with morphologic manifestations characteristic of it may occur.
Figure 2. Stages of development of hypertension.

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Preclinical stage of hypertension

It is characterized by periodic, temporary increase in blood pressure
(transient hypertension). Microscopic examination reveals moderate
hypertrophy of the muscle layer and elastic structures of arterioles and small
arteries, spasm of arterioles or fibrinoid necrosis in hypertensive crisis.
Clinically and morphologically, moderate compensatory hypertrophy of the
left ventricle of the heart is detected.
Stage of pronounced widespread morphologic changes of

arterioles and arterioles
It is the result of a long-term persistent increase in blood pressure. In
this stage, morphologic changes occur in arterioles, arteries of elastic,
muscular-elastic and muscular types, as well as in the heart. The most
characteristic sign of hypertension is changes in arterioles, manifested as
plasmatic impregnation, with a transition to arteriolosclerosis and hyalinosis
("bulbous sclerosis"). Changes in the vessels are accompanied by the
formation of atherosclerotic plaques located circularly.
Most often plasmatic impregnation and hyalinosis affect arterioles and
small arteries of kidney, brain, pancreas, intestine, retina, and adrenal
capsule.
Elastosis and elastofibrosis are defined in arteries of elastic,
muscular-elastic and muscular types.
Elastosis and elastofibrosis are successive stages of the process and
represent hyperplasia and cleavage of the internal elastic membrane, which
develops compensatory in response to a persistent increase in blood pressure.
Subsequently, elastic fibers die and are replaced by collagen fibers, i.e.,
sclerosis. The vessel wall thickens, the lumen is narrowed, leading to the
development of chronic ischemia in the organs. Changes in arterioles and
arterioles of muscular-elastic and muscular types create prerequisites for the
development of the third stage of hypertension.
At this stage, the heart mass reaches 900-1000 g, and the thickness of
the left ventricular wall is 2-3 cm. Due to myocardial trophic disturbance
(under conditions of oxygen starvation), diffuse small-focal cardiosclerosis
develops.
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Stage of secondary changes in internal organs

This stage is due to vascular changes and impaired intra-organ
circulation. These secondary changes can manifest themselves either very
quickly as a result of spasm, thrombosis, fibrinoid necrosis of the vessel wall
and end in hemorrhages or infarcts, or they can develop slowly as a result of
hyalinosis and arteriolosclerosis and lead to parenchyma atrophy and organ
sclerosis.
Clinical and morphologic forms
1. The cerebral form of hypertension together with atherosclerosis of
cerebral arteries are the morphologic basis of cerebrovascular disease.
In hypertensive crisis in the brain, fibrinoid necrosis leads to rupture
of the vascular wall and hemorrhage (hematoma), clinically
manifested as hemorrhagic stroke. With a benign prolonged course of
hypertension, brain atrophy develops. Unlike ischemic stroke in
atherosclerosis, which may be due not only to ischemic but also
hemorrhagic infarction, hemorrhage develops in living rather than
dead tissue. Therefore, the brain tissue near the focus of hemorrhage is
shiny. In hemorrhagic infarction, brain tissue is unevenly stained with
blood, dull, often softened.
2. The cardiac form of hypertension together with the cardiac form of
atherosclerosis constitute the essence of coronary heart disease. As a
result of narrowing of the lumen of arterioles in hypertension and,
consequently, increased resistance to blood flow, a "bull's heart"
develops - hypertrophy of the left ventricle of the heart, later joined by
hypertrophy of the right ventricle. The mass of the heart can reach 500
g or more. At compensation of cardiac activity there is tonogenic
dilatation of ventricular cavities, at decompensation - myogenic.
Microscopically in the stage of compensation cardiomyocytes have
large hyperchromic nuclei. In decompensation, cardiomyocyte
dystrophy and interstitial sclerosis are observed.
3. The renal form of hypertension is characterized by both acute and
chronic changes.
• acute form:
The kidneys appear somewhat reduced in size, mottled, and
their surface is fine-grained. Renal infarcts and
arteriolonecrosis, which are associated with
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by thromboembolism or arterial thrombosis. Arteriolonecrosis

leads к acute renal renal failure и
usually ends fatally.
Arterioles and capillary loops of the tubules with fibrinoid

necrosis, edema and hemorrhages in the stroma, protein
dystrophy in the tubule epithelium. In response to necrosis,
cellular reaction and sclerosis develop in arterioles, tubules and
stroma.
• chronic form:
Kidneys sharply decrease in size (practically twice), dense,
their surface is fine-grained, parenchyma is uniformly thinned,
especially the cortical substance. The mass of kidneys can
reach 50-60 grams. Such kidneys are called "primary shriveled
kidneys" ("arteriolosclerotic nephrosclerosis"). Patients most
often die in this form from chronic renal failure (azotemic
uremia).
As a result of insufficient blood supply and hypoxia, the tubule

part of most nephrons atrophies and is replaced by connective
tissue, which grows also around the dead tubules. On the
surface of the kidneys appear small multiple foci of depression.
Nephrons corresponding to relatively intact tubules,
hypertrophied and protrude above the renal surface.
Changes in the eyes in hypertension are secondary and associated

with typical vascular changes. These changes manifest themselves in the
form of edema of the optic nipple, hemorrhages, retinal detachment, in
severe cases its necrosis and severe dystrophic changes in nerve cells of the
ganglionic layer.
The most common cause of death is heart failure due to diffuse
cardiosclerosis (in acute cases - myocardial infarction), chronic renal failure
(azotemic uremia), cerebral hemorrhage.
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► CORONARY ARTERY DISEASE HEART◄
Coronary heart disease (CHD) is a group of diseases caused by

absolute or relative insufficiency of coronary circulation.
CHD was singled out as an "independent disease" by the World Health
Organization in 1965 due to its great social significance. Coronary artery
disease is now widespread throughout the world, especially in economically
developed countries. The danger of ischemic heart disease lies in the rapid
death. It accounts for about 2/3 of deaths from cardiovascular diseases. Men
aged 40-65 years are more often affected.
Coronary heart disease is a cardiac form of atherosclerosis and
hypertension manifested by myocardial ischemic degeneration, myocardial
infarction, and cardiosclerosis.
CHD proceeds in a wave-like manner, accompanied by coronary
crises, i.e. episodes of acute (absolute) coronary insufficiency occurring
against the background of chronic (relative insufficiency of coronary
circulation). In this regard, acute and chronic forms are distinguished (see
Fig. 3):
Figure 3. Classification of ischemic heart disease.

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Myocardial ischemic dystrophy (acute

focal myocardial dystrophy)
It develops in relatively brief episodes of coronary crisis, when there
are characteristic changes in the electrocardiogram in the absence of
myocardial necrosis (no increase in the activity of transaminases, lactate
dehydrogenase, etc.).
The myocardium is flabby and pale, sometimes mottled and

edematous in areas of ischemia. Often a fresh thrombus is
found in the coronary artery.
Dilatation of capillaries, stasis and sludge phenomenon of

erythrocytes, interstitial edema, perivascular hemorrhages,
accumulation of leukocytes at the periphery of the ischemia
zone. Muscle fibers lose transverse striation, are devoid of
glycogen, they are intensely stained with eosin, fuchsin,
pyronin and Schiff's reagent, which indicates necrobiotic
changes.
The complication of ischemic myocardial dystrophy is most often acute heart
failure, it also becomes the immediate cause of death.
Myocardial infarction
Myocardial infarction is ischemic necrosis of the heart muscle. It is
usually ischemic (white) infarction with a hemorrhagic corolla.
17
Figure 4. Classification of myocardial infarction.
Myocardial infarction is commonly categorized according to a

number of features:
• by time of occurrence:
- primary (acute) myocardial infarction - lasts about 6 weeks from
the onset of myocardial ischemia;
- recurrent heart attack. - infarction of the
myocardium, developed 6 weeks after the primary (acute)
infarction;
- recurrent infarction - an infarction that has occurred during
6 weeks existence primary (acute)
myocardial infarction.
• localization: myocardial infarction is localized most often in the
region of the apex, anterior and lateral walls of the left ventricle and
anterior parts of the interventricular septum, i.e. in the basin of the
anterior interventricular branch of the left coronary artery, which is
functionally more aggravated and more affected by atherosclerosis
than other branches. Less frequently, infarction occurs in the area of
the posterior wall of the left ventricle and posterior parts of the
interventricular septum, i.e. in the basin of the envelope branch of the
left coronary a r t e r y . When
18
The main trunk of the left coronary artery and both of its branches are
subjected to atherosclerotic occlusion, and extensive myocardial
infarction develops. Infarction in the right ventricle and, especially, in
the atria is rare.
• by prevalence: when the endocardium is involved in the necrotic

process (subendocardial and transmural infarcts), reactive
inflammation develops in its tissue, thrombotic deposits appear on the
endothelium. In subepicardial and transmural infarcts there is often a
reactive inflammation of the outer membrane of the heart - fibrinous
pericarditis.
Morphogenesis of myocardial infarction

Morphogenesis of myocardial infarction is characterized by a
sequential change of three stages: ischemic, necrotic, and scarring stages.
1. Ischemic stage: acute ischemia, fatty and protein dystrophy
progressing to necrobiotic changes of cardiomyocytes.
2. Necrotic stage:
A pale nidus with irregular blood flow around the area
The area of necrosis is delimited from the preserved

myocardium by a zone of full blood loss and leukocytic
infiltration (demarcation inflammation). Outside the focus of
necrosis is noted irregular blood filling,
hemorrhages, disappearance of glycogen from cardiomyocytes,
appearance of lipids in them, destruction of mitochondria and
sarcoplasmic network, necrosis of single muscle cells, small
areas of preserved cardiomyocytes are revealed perivascularly.
3. Scarring stage (organization):

The infarction acquires clear boundaries and a yellowish color.
The newly formed connective tissue is at first loose,
granulation tissue type, and then matures into dense coarse-
fibrous scar tissue of whitish-gray color.
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Infarct organization occurs both from the demarcation zone and

from "islets" of preserved tissue in the necrosis zone. This
process lasts 7-8 weeks, however, these terms are subject to
fluctuations depending on the size of the infarct and the
reactivity of the patient's organism. When the infarction is
organized, a dense scar is formed in its place. In such cases, we
speak about postinfarction large-focal cardiosclerosis. The
preserved myocardium, especially around the periphery of the
scar, undergoes regenerative hypertrophy.
Complications of myocardial infarction:
• Cardiogenic shock when more than 40% of the ventricular
area is affected;
• acute heart failure when 20-25% of the ventricle is affected;
• myomalacia (melting of the infarction zone by leukocytes) in 4-6
days after an attack of ischemia with rupture of the ventricular wall
and cardiac tamponade;
• wall thrombus in the ventricular cavity with possible
thromboembolism to the brain;
• fibrinous pericarditis;
• development of acute or chronic (at the scar site) ventricular
aneurysm in the setting of transmural infarction;
• Dressler's syndrome is an autoimmune complication of
myocardial infarction.
Fig. 5. Schematic representation of changes in myocardial infarction: A -
normal;
Б - 12-18 hours (eosinophilia of cardiomyocytes, onset
of necrobiotic changes);
В - 1 24 hours (necrobiotic changes cardiomyocytes,
infiltration with polymorphonuclear leukocytes);
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D - 3 weeks (peripheral areas of infarction are formed by granulation tissue

with a large number of capillaries, fibroblasts, lymphoid cells and
macrophages);
D - 3 months (the infarct area is replaced by rough fibrous connective tissue
[scar]).
Chronic forms of coronary heart disease
These forms are characterized by diffuse or widespread focal
cardiosclerosis. It is possible to develop a chronic cardiac aneurysm with the
organization of transmural infarction. It can cause relative insufficiency of the
mitral valve and hypertension of the small circle of circulation. Clinically,
chronic CHD manifests itself as angina pectoris.
► CARDIOMYOPATHIES◄
Cardiomyopathies are a group of diseases based on primary

dystrophic changes in the myocardium. The main clinical sign of
cardiomyopathies is myocardial contractile function failure due to
myocardial dystrophy.
There are primary (idiopathic) and secondary diseases

cardiomyopathies.
Figure 6. Classification of primary cardiomyopathies.
• Hypertrophic (constrictive) cardiomyopathy is a pronounced

hypertrophy of myocardium mainly of the left ventricle of the heart,
with reduction of ventricular cavities. It is a hereditary disease that
affects mainly men, with the onset of clinical manifestation at an
average age of 40 years.
- Obstructive or localized cardiomyopathy (idiopathic hypertrophic
subaortic stenosis) - myocardial hypertrophy covers mainly the
upper
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sections of the left ventricle, resulting in subaortic narrowing;

- non-obstructive or diffuse cardiomyopathy (idiopathic myocardial
hypertrophy) - diffuse thickening of the myocardium of the left
ventricle and interventricular septum; microscopically - chaotic
arrangement of cardiomyocytes, especially in the interventricular
septum.
• Dilated (congestive) cardiomyopathy is a diffuse myocardial lesion
with enlargement of heart cavities and reduction of its contractile
function. The disease is associated with Coxsackie virus, accounts for
60% of all idiopathic cardiomyopathies, and is most often observed in
men aged 10-30 years.
• Restrictive cardiomyopathy is a myocardial lesion characterized by
stiffness of the ventricular walls of the heart (more often the left
ventricle) and marked endocardial fibrosis, which prevents diastolic
filling and leads to impaired atrioventricular valve function.
Secondary cardiomyopathies occur in intoxications (alcohol, uremia),
infections, metabolic disorders (thesaurismoses), diseases of the digestive
organs (cirrhosis of the liver, pancreatitis). Morphologically, secondary
cardiomyopathies are manifested as moderate myocardial hypertrophy,
dilated heart cavities with the presence of wall thrombi.
Complications of cardiomyopathies:
• chronic heart failure;
• thromboembolic syndrome due to the presence of blood clots in
the heart cavities;
• sudden death due to ventricular fibrillation.
► CEREBROVASCULAR DISEASES◄
Cerebrovascular diseases - a group of diseases characterized by

acute disorders of cerebral circulation, the morphological basis of
which are atherosclerosis and hypertension.
22
Figure 7. Classification of cerebrovascular diseases.

23
SECTION II
RHEUMATIC DISEASES
Peuvmučecue diseases (cucumeme diseases of the medulla) are

a group of diseases that are characterized by damage to the
connective tissue due to changes in immune homeosmosis, which
leads to aymoimmunization, formation of moxic immune
complexes and sensitized cells damaging the
microcypocypocyclamellar channel.
The emuologuucccal factors common to rheumatic diseases are:

• chronic infection (bacterial or viral in nature);
• genetic factors;
• exogenous factors (hypothermia, insolation, use of medications).
The pamogenesis of all rheumatic diseases is based on immediate and
delayed hypersensitivity reactions. A simplified pathogenesis of these
diseases is schematically presented i n Fig. 8.
Fig. 8. General pathogenesis of rheumatic diseases.

24
In turn, systemic progressive disorganization of connective tissue proceeds

in the form of 4 consecutive phases:
1) mucoid swelling;
2) fibrinoid changes;
3) an inflammatory cellular response;
4) sclerosis.
Individual nosologic forms of rheumatic diseases (systemic connective

tissue diseases):
• rheumatism;
• systemic lupus erythematosus;
• rheumatoid arthritis;
• systemic scleroderma;
• periarteritis nodosa;
• Bechterew's disease;
• dermatomyositis;
• Sjögren's syndrome;
• et al.
►RHEUMATISM
Rheumatism (Sokolsky-Buŭo disease; acute rheumatic fever) is a

systemic inflammatory disease of connective tissue of infectious
and allergic nature with a wave-like course and predominantly
localization of the pathological process in the cardiac membranes
and vessels.
ETHIOCOGIA.
Currently, β hemolytic streptococcus group A (Streptococcus
haemolyticus) is considered as the main etiologic factor - frequent, recurrent
infectious diseases caused by this microorganism: pharyngitis, sore throat,
scarlet fever, etc. The so-called "rheumatogenic" strains of streptococcus
(M1, M3, M5, M18, M24) are of particular importance. Of particular
importance are the so-called "rheumatogenic" strains of Streptococcus (M1,
M3, M5, M18, M24), which have the following properties:
- tropism to the nasopharyngeal tissue;
- ability to induce the synthesis of type-specific antibodies;
- high contagiousness;
- The presence of M-protein on the surface of the microorganism.
25
M-protein has the properties of a "superantigen" that induces an autoimmune

response. This response may be enhanced by subsequent infection with
group A β hemolytic streptococcus.
Risk factors for the development of acute rheumatic fever:
• ages 7-20;
• female gender;
• heredity;
• prematurity;
• congenital collagenopathies;
• acute streptococcal infection and frequent nasopharyngeal
infections;
• unfavorable working conditions or living in a room with high
humidity, low air temperature.
PATHOGENESIS.
The scheme of pathogenesis of rheumatism is presented in Fig. 9.
Figure 9. Pathogenesis of rheumatism.
In the pathogenesis of rheumatism, the main significance is the

antigenic similarity (mimicry) of Streptococcus antigens (M-protein) and
own antigens of myocardium, connective tissue of heart valves and joints.
Exposure to toxins and enzymes of streptococcus, a
26
also immune response to microorganism antigens leads to "exposure" of own

antigens and development of autoimmune process by type of immediate
hypersensitivity reactions (IHR) and delayed hypersensitivity reactions
(DHT). Immediate hypersensitivity reaction is characterized by acute
immune inflammation in the form of exudative-necrotic vasculitis.
Gradually, the DST reaction is replaced by a delayed-type hypersensitivity
reaction, within which sclerosis of vessels and perivascular connective tissue
develops. In this regard, the changes in rheumatism are chronic and wave-
like in nature, which is determined by the development and periodic change
of HHT and HHT reactions.
CLINIC, DIAGNOSTIC CRITERIA

For to make diagnosis rheumatism (first attack) The
Jones criteria have been proposed:
• big criteria:
- carditis;
- polyarthritis;
-chorea (small);
-circular erythema;
-subcutaneous rheumatic nodules;
• small criteria:
- fever;
- arthralgia;
-increase in indicators of the acute phase of inflammation:
COE, C-reactive protein, etc.;
-lengthening of the PR interval on the ECG.
Any 2 major criteria or 1 major criterion and 2 minor criteria are
sufficient to make a diagnosis of rheumatism.
Also, depending on the peculiarities of the predominant localization
and manifestations, the following clinical and morphological forms of
rheumatism are distinguished (Fig. 10):
• cardiovascular form - the most frequent form, characterized by
predominant heart involvement (see below).
• polyarthritic form - characterized by the lesion of large joints with the
development of foci of disorganization in the synovial membrane
(synovitis), vasculitis with hyperemia of vessels, perivascular
lymphoid infiltrates in the form of clutches, the appearance of serous
and serous-fibrinous effusion in the joint cavity. Articular cartilage is
not involved in the process,
27
Therefore, joint deformation does not occur in rheumatism ("volatile

polyarthritis");
• nodose (nodular) form - characterized by the appearance of nodules
under the skin on the extensor side of large joints, along the spinal
column, in the fascia, aponeurosis and tendons, consisting of a focus
of fibrinoid necrosis surrounded by an infiltrate of lymphocytes and
macrophages. Small scars are formed in the outcome;
• cerebral form ("little chorea") - mainly in children. Arteritis,
microglial nodules, dystrophic changes in nerve cells, and
occasionally foci of hemorrhage are found in the brain. The changes
are accompanied by muscle weakness and impaired coordination of
movements;
• erythematous form - characterized by the appearance of so-called
"ring-shaped erythema" - a rash in the form of pale pink rings on the
skin of the chest and abdomen. The rash is not accompanied by
itching, does not rise above the skin surface, quickly disappears
without pigmentation and peeling;
• visceral form - with predominant involvement of internal organs and
serous membranes (polyserositis).
MORPHOGENESIS
As in all systemic diseases of connective tissue, there are 4 phases in
the development of morphological changes in rheumatism:
1. Mucoid swelling is a superficial and reversible disorganization of
connective tissue characterized by accumulation and redistribution of
mucopolysaccharides and glycoproteins (see section "Stromal and
vascular protein dystrophies"). It corresponds to the phase of
development of immediate hypersensitivity reactions.
2. Fibrinoid changes (fibrinoid swelling and fibrinoid necrosis) - deep
and irreversible disorganization of connective tissue, characterized by
homogenization of collagen fibers and their impregnation with plasma
proteins, including fibrin (see sections "Stromal-vascular protein
dystrophies", "Necrosis"). Corresponds to the phase of development of
immediate hypersensitivity reactions.
28
Figure 10. Clinical and morphologic forms of rheumatism.
3. Inflammatory cellular reaction - characterized by the formation of

specific rheumatic granulomas (Aschoff-Talalaev granulomas) (Fig.
11), which undergo several stages in their development:
• granuloma stage;
• mature ("blooming") granuloma stage;
• stage of scarring ("fading") granuloma.
29
Figure 11. Schematic structure of Aschoff-Talalaev granuloma.
In the center of the granuloma there is a focus of fibrinoid

necrosis (amorphous eosinophilic masses). Around the focus of
necrosis - lymphocytic and plasmacytic infiltration, large
macrophages with basophilic cytoplasm and round or oval
nuclei with central chromatin arrangement (owl's eye cells) or
chromatin arrangement in cells in the form of a "caterpillar"
(caterpillar cells) (Anichkov cells). Sometimes there are
multinucleated histiocytes (multinucleated giant Aschoff cells).
Further on, there are large macrophages
are replaced by fibroblasts, and sclerosis develops.
4. Sclerosis - characterized by an overgrowth of connective tissue:

• Primary sclerosis (cell-free) - develops as an outcome of
fibrinoid swelling and/or necrosis;
• secondary sclerosis (cellular) - occurs as a result of
maturation and fibroplastic transformation of cellular
infiltrates (rheumatic granulomas).
Sclerosing in rheumatism is progressive in nature.
MORPHOLOGY
The most pronounced morphologic changes in rheumatism are
manifested in the heart. Heart damage in rheumatism can occur in the form
of endocarditis, myocarditis, pericarditis or pancarditis (lesions of all heart
membranes).
30
Rheumatic endocarditis Classification:

• by localization:
-valvular withpredominant lesion of the valves (more often
- mitral valve; less often - aortic valve);
- chordal - с predominantly with
predominantly tendon filaments;
-pristenotic - with predominant lesion of the endocardium of the
heart cavities;
• downstream:
- sharp;
- chronic;
• by clinical and morphologic form (can be presented in the form of
consecutive phases of endocardial lesions):
- diffuse (simple) endocarditis (valvulitis) - endocarditis without
endothelial damage, without thrombus formation;
The valve is unchanged or slightly thickened due to edema
along line of closure, grayish color,
translucent.
Diffuse mucoid swelling (metachromasia phenomenon),

fibrinoid changes in connective tissue of valve flaps and
granuloma formation without damage
of endothelium and thrombotic deposits.
- acute wart endocarditis - accompanied by endothelial damage and
formation of thrombotic deposits in the form of "warts" along the
closing edge of the flaps (in the areas of endothelial damage);
Heart size and weight are not changed; valve leaflets are
moderately thickened, edematous, with small (2-3 mm) dark
red color, crumbling thrombotic deposits (in the form of
"warts") along the free margin
of the flaps (in foci of endocardial damage of the valve flaps).
In the valve stroma there are areas of connective tissue

disorganization in the form of fibrinoid swelling and fibrinoid
necrosis, on the endocardial surface there is an overlay of
thrombotic masses. Diffuse
histiolymphocytic infiltration.
31
- Fibroplastic endocarditis - develops as a consequence of the

previous two forms of endocarditis with a tendency to fibrosis and
scarring;
Flaps of the valve thickened,
shortened, dense consistency, deformed, gray
color,
translucent.
There are large foci of sclerosis and hyalinosis in the valve

stroma.
- Recurrent beard endocarditis - characterized by layering of fresh
alterative-proliferative changes with thrombosis on old sclerotic
processes.
Heart size and weight may be increased (myocardial
hypertrophy). The valve leaflets are thickened, deformed,
whitish in color. Small thrombotic deposits of red color (in the
form of warts) along the free edge of the sclerosed, deformed,
partially fused
and petrified mitral valve flaps (in
the foci of endocardial damage of the valve flaps). Chordae are
thickened, fused, shortened ( rheumatic malformation).
of the heart).
The valve leaflets are sclerosed, hyalinosis is observed. Areas

of mucoid swelling and fibrinoid necrosis, with weakly
expressed lymphohistiocytic infiltration. Appearance of newly
formed vessels. В
in areas of endocardial damage-- clotting.
Complications - thromboembolism (in acute and age-related warty
endocarditis):
• vessels of the great circle of blood circulation (in case of mitral or
aortic valve damage - the most frequent) - infarcts of the spleen,
kidneys, brain, myocardium, retina, etc.;
• vessels of the small circulatory circle (in case of tricuspid heart valve
or pulmonary trunk valve damage - extremely rare) - pulmonary
embolism.
The outcome of rheumatic endocarditis is sclerosis, hyalinosis, petrification
and deformation of valve flaps with the development of heart defects (see
below).
32
Rheumatic myocarditis
The following clinical and morphologic forms of rheumatic
myocarditis are distinguished:
• nodular productive (granulomatous) myocarditis - characterized by
the formation of rheumatic granulomas (Aschoff-Talalaev
granulomas) in the perivascular connective tissue of the myocardium
(see above);
• diffuse interstitial exudative myocarditis
Heart cavities are sharply dilated (myogenic dilatation of
ventricular cavities), myocardium is flabby, dull.
The vessels are full-blooded, myocardial interstitium is

saturated with serous exudate, infiltrated with lymphocytes,
histiocytes, polymorphonuclear leukocytes.
Muscle fibers unfold, in cardiomyocytes - pronounced
dystrophic changes.
• focal interstitial exudative myocarditis
Minor focal infiltration of the myocardium with lymphocytes,

histiocytes and neutrophils.
Complications - acute heart failure (most typical for diffuse interstitial
exudative myocarditis), due to a sharp decrease in myocardial contractile
activity, arrhythmias.
The outcome of rheumatic myocarditis is diffuse cardiosclerosis.
Rheumatic pericarditis
Pericardial lesions in rheumatism have the character of serous, serous-
fibrinous or fibrinous inflammation. According to this, they distinguish:
• serous pericarditis;
• serous fibrinous pericarditis;
• fibrinous pericarditis.
Both pericardial sheets are full bloody, edematous, covered
with fibrinous plaque (in serous-fibrinous and fibrinous
pericarditis). The pericardial cavity is s e r o u s , serous-
fibrinous or
fibrinous exudate. In severe fibrinous pericarditis - massive
fibrin deposits in the form of filaments
33
("hairy heart").
Mucoid swelling and fibrinoid changes of connective tissue,

foci of cellular infiltration. There are areas of fibrin deposition
on the epicardial surface.
In rheumatism develops a sharp sclerosis of the serous sheets of the
pericardium, obliteration of the cavity, deposition of calcium, ie, the
occurrence of the so-called "shell heart".
ACQUIRED HEART DEFECTS

As stated earlier, the main outcome of rheumatic heart disease (in
particular, endocardial damage) is the formation of heart defects.
Acquired heart defects (valve defects) are disorders of the heart
caused by morphologic and/or functional changes in one or more
of its valves. They are the result of infectious lesions,
inflammation or autoimmune reactions, overloading and
dilatation of the heart chambers.
The following is a classification of acquired heart defects (Figure 12).

Figure 12: Classification of acquired heart defects.
In acquired heart defects, the deformity may involve various elements

of the valve:
• the fibrous rings on which the flaps are fixed;
34
• chords;
• papillary muscles.
A distinction is made between stenosis of the valve orifice,
insufficiency of the flaps or valve pockets, and a combination of these
changes:
- Valve orifice stenosis - occurs when the pockets or flaps fuse together;
- valve orifice insufficiency - occurs due to shortening of the flaps or
may be due to dilation of the fibrous ring without flap shortening.
- combination of stenosis and insufficiency - characterized by stiffness
of the flaps or valve pockets, when the valve opening is narrow and
presents a non-closing slit ("jacket loop" or "fish mouth").
In mitral valve stenosis there is: hypertrophy of the left atrium (due to
narrowing of the left atrioventricular orifice) → difficulty of blood outflow
through the pulmonary veins (chronic pulmonary venous hyperemia) →
increased pressure in the pulmonary arteries (pulmonary hypertension) →
right ventricular hypertrophy (with subsequent decompensation and
development of right ventricular heart failure).
In mitral valve insufficiency, there is: hypertrophy of the left atrium
and left ventricle (due to backflow of blood from the left ventricle into the
left atrium through the nonclosing valve, with subsequent decompensation of
the left ventricle) → obstruction of blood outflow through the pulmonary
veins (chronic pulmonary venous hyperemia) → increased pressure in the
pulmonary arteries (pulmonary hypertension) → right ventricular
hypertrophy (with subsequent decompensation and development of right
ventricular heart failure).
In aortic valve defects, marked left ventricular hypertrophy is
observed. In decompensation and expansion of its cavity, relative
insufficiency of the mitral valve may occur → right ventricular hypertrophy
joins.
The degree of compensation of the heart defect is judged by the
character of cavity dilatation:
• tonogenic dilatation - develops due to increased pressure in the heart
chambers as a result of excessive blood flow. The muscle wall remains
normal for some time;
35
• myogenic dilatation - appears with various changes in the heart

muscle. In this case, the contractility of myocardium is reduced.
Decompensation is also manifested by the presence of
parenchymatous dystrophy of the most aggravated part of the heart (up to the
"tiger heart").
In left ventricular failure due to bicuspid valve malformations,
depending on the rate of its development, there are pulmonary edema or
"brown induration of the lungs" if decompensation developed slowly.
In right ventricular insufficiency due to predominant lesion of the
tricuspid valve, as well as in the case of decompensation of mitral
malformations, there is stasis in the great circle of blood circulation, a typical
manifestation of which is "muscat liver".
► SYSTEMIC RED LUPUS ERYTHEMATOSUS◄
Systemic lupus erythematosus (SLE, Liebman-Sachs disease) is a

systemic connective tissue disease characterized by diffuse
immunocomplex damage to connective tissue, with predominant
involvement of the skin, blood vessels and kidneys.
ETHIOPATHOGENESIS
The etiopathogenesis of SLE is schematically presented in Fig. 13.
The pathogenesis of SLE is based on immune inflammation caused by

autoantibodies directed against the DNA of host cells, followed by the
formation of circulating immune complexes, which settle on the vessels of
the microcirculatory channel and cause tissue damage.
36
Figure 13: Etiopathogenesis of systemic lupus erythematosus.
MORPHOGENESIS
In general, corresponding to the 4 phases of connective tissue
disorganization, the development of morphological changes in SLE can be
divided into 5 groups:
1. Acute necrotic and dystrophic changes of connective tissue - all
stages of progressive disorganization of connective tissue (mucoid
swelling, fibrinoid swelling, hyalinosis), fibrinoid necrosis of
microcirculatory vessels.
2. Subacute interstitial (interstitial) inflammation of all organs,
including the nervous system and serous membranes (polyserositis),
with involvement of microcirculatory vessels and formation of
inflammatory infiltrate of lymphocytes, macrophages and plasma
cells.
37
3. Sclerosis - develops as a result of disorganization of connective tissue

and interstitial inflammation. A typical manifestation is periarterial
("bulbous") sclerosis in the spleen.
4. Changes in the immune system organs - in the bone marrow, lymph
nodes, spleen there are focal accumulations of lymphocytes and
plasma cells; there is hyperplasia of the thymus and other lymphoid
organs.
5. Nuclear pathology - nuclei gradually lose DNA and become pale with
subsequent disintegration into clumps ("hematoxylin cells").
Appearance of antinuclear antibodies ("lupus factor") → neutrophils
and macrophages phagocytize cells with damaged nuclei to form so-
called "lupus cells" (LE cells).
MORPHOLOGY
Morphologic manifestations in SLE are extremely diverse, as well as
clinical manifestations and the course of the disease. At the same time, the
most characteristic changes are identified in the kidneys, blood vessels and
skin.
Morphologic changes in the kidneys
Macroscopic changes depend on the stage and severity of the

process:
- at the initial stage (active glomerulonephritis) - the kidneys
are significantly increased in size, flabby, the cortical
layer is wide, swollen, yellowish-gray with numerous red
dots, dull, well delimited from the dark red brain matter
("big mottled kidney");
- at a late stage (nephrosclerosis) - kidneys are reduced in
size, compacted, the surface is fine-grained with full
blood vessels and
with foci of hemorrhaging.
According to the modern classification, there are 5 main classes of renal changes.
• Grade 1 - minimal mesangial lupus nephritis - changes
are minimal, often not detectable at the light-optical
level;
• Grade 2 - mesangial proliferative.
38
Lupus nephritis - characterized by proliferation of

mesangial cells and deposition of immune complexes
without involvement of capillaries of the vascular
tubercle;
• Grade 3 - focal lupus nephritis - segmental
intracapillary or
extracapillary glomerulonephritis with less than 50% of
tubules affected: formation of "half moons", fibrinoid
necrosis, proliferation of
endothelial and mesangial cells, lymphocytic infiltration.
• Grade 4 - diffuse lupus nephritis - similar changes with
more than 50% of the tubules affected (the most severe
form of lupus nephritis).
• Class 5 - membranous lupus nephritis - is characterized
by diffuse thickening of capillary walls of vascular
tubules. Due to the deposition of immune complexes, the
capillary walls of the vascular tubercle thicken and look
like "wire loops".
- + sclerosing lupus nephritis - predominance of sclerosis
processes in the vascular tubules of the kidneys.
Morphological changes in the skin

Symmetrical maculopapular rash on back of nose and
red "butterfly" shaped cheeks with a bluish tinge. Other skin
manifestations are also possible: thick red scaly patches on the
skin ("discoid lupus e r y t h e m a t o s u s "), alopecia areata, etc.
Lymphohistiocytic infiltrate around the venules and the

skin appendages, dilation of vessels and hemorrhages,
thickening of the basal membrane and atrophy of the epidermis,
hyperkeratosis
Morphologic changes in the vasculature and heart

Liebman-Sachs endocarditis: small thrombotic
red deposits in the form of "warts" along the free edge of
sclerosed and deformed valve flaps (mainly mitral).
39
Vessels change according to the type of periarterial "bulbous"

sclerosis (in the spleen): layered ring-like overgrowth of
collagen fibers in the form of a coupling around sclerosed
arteries and arterioles. Disseminated phenomena of vasculitis.
The heart is mainly affected by pericarditis or Libman-Sachs
endocarditis (abacterial warty endocarditis, atypical lupus
endocarditis): the valve flaps and chords and the walled
endocardium are affected. In the myocardium -
parenchymatous fatty dystrophy, less often - diffuse
proliferative interstitial myocarditis.
Morphological changes in other organs and systems

Clinical and morphological manifestations SLE
are diverse and, in addition to those
described above, may include:
• Polyserositis (lesions of the pleura, pericardium, peritoneum);
• Arthritis of the small joints of the hands, wrist and ankle joints;
• meningoencephalomyelitis и productive sciatica,
neuritis, plexitis;
• generalized lymphadenopathy, enlargement spleen,
atrophy of lymphoid follicles;
• lymphocytic и plasmacytic infiltration, fatty
degeneration of the liver;
• et al.
Chronic renal failure (nephrosclerosis as an outcome of lupus nephritis).
Chronic heart insufficiency (asoutcome endocardial
damage with the formation of valve insufficiency or as an outcome of
myocarditis with the formation of diffuse cardiosclerosis). "Lupus" crisis -
manifestation highest of the highest degree
of the lupus process. Crises can occur in any course of the
disease. и characterized pronounced clinical
and morphologic changes.
Purulent-septic complications - often due to active glucocorticoid therapy.
40
► RHEUMATOID ARTHRITIS◄
Rheumatoid arthritis is a chronic systemic connective tissue

disease with progressive lesions of predominantly peripheral
joints in the form of erosive-destructive polyarthritis.
The etiopathogenesis of rheumatoid arthritis as well as its clinical and

morphologic forms are schematically summarized in Figure 14.
Figure 14: Etiopathogenesis and clinical and morphologic forms of

rheumatoid arthritis.
Morphologic changes in the joints The small joints of the hands are
predominantly affected. Morphogenesis can be divided into 3 stages:
• Stage 1 (acute inflammatory reaction)
Increase in vascular-tissue permeability, edema, synovial
membrane fullness, mucoid swelling, fibrin deposition, foci of
fibrinoid
necrosis ("rice balls"). In vessels there is proliferative
vasculitis, thrombovasculitis with
41
predominantly affecting the venules.

• Stage 2 (hyperplasia and hypertrophy of the synovial membrane)
Expansion of granulation tissue in the subsynovial layer
("pannus"). Focal lymphocytic-plasmacytic infiltration.
Destruction of cartilage with formation of cracks
and sequestration.
• Stage 3 (fibrous bone ankylosis)
Visceral (extra-articular) manifestations

• polyserositis;
• heart and vessels: focal endocarditis, vasculitis, cardiomyocyte
dystrophy, cardiosclerosis;
• Lungs: vasculitis, interstitial pneumonia, pneumosclerosis;
• gastrointestinal tract: atrophy mucosa due to
vasculitis and productive inflammation;
• Liver: parenchymatous dystrophy, interstitial hepatitis, fibrosis,
amyloidosis;
• kidneys: acute and chronic glomerulonephritis, amyloidosis;
• et al.
Chronic renal failure (nephrosclerosis as an outcome of rheumatoid
glomerulonephritis, renal amyloidosis).
Purulent-septic complications - often due to active glucocorticoid therapy.
Limitation of joint mobility due to fibrous-bone ankylosis, formation of
dislocations / subluxations.
► SYSTEMIC SCLERODERMA◄
Systemic scleroderma is a systemic disease of connective tissue

and small vessels, characterized by widespread fibrotic-sclerotic
changes in the skin, stroma of internal organs and symptoms of
obliterative endarteritis in the form of widespread Raynaud's
syndrome.
ETHIOPATOGENESIS
Systemic scleroderma - polyetiologic disease
with a key role of immunopathologic processes.
В underlying pathogenesis - fibrosis through Increased
collagen-forming function of fibroblasts with increased production of
42
collagen type I and IIII, fibronectin, proteoglycans and glycoproteins.

Disturbance of microcirculation, endothelial damage, adhesion and
aggregation of blood cell elements, microthrombosis → generalized
Raynaud's syndrome.
Morphological changes in the skin

• Stage 1 (dense edema stage)
Increased vascular permeability. Hydropic dystrophy of cells of
the basal layer of the epidermis, unfolding of collagen bundles
of the dermis due to edema, vasculitis, lymphohistiocytic
inflammatory infiltration around vessels, appendages of the
skin and in the
subcutaneous tissue.
• Stage 2 (induration/sclerosis stage)
Sclerosis of the papillary and reticular layers of the dermis with
capillary desquamation, sclerosis of vessel walls, reduction in
the number of cells, thickening of collagen layers
bundles, hyalinosis.
• Stage 3 (atrophy stage)
Skin tension, kissing folds around the mouth, flexion
contractures, sclerodactyly, osteolysis of individual phalanges.
Fields of hyalinized tissue with diffuse atrophy of epidermis,

smoothing of papillae, sharp desolation of microcirculatory
vessels, reduction in the number of cells, atrophy of appendages
skins.
Morphological changes in other organs and tissues

• joints - decreased amount of synovial fluid, multiple thrombosis of
superficial capillary network, fibrinoid on the surface of synovial
membrane;
• heart - hypertrophy, cavity enlargement, thickening and whiteness of
the walled endocardium, valve sclerosis, cardiosclerosis;
• lungs - interstitial pneumosclerosis (cystic, compact);
• kidneys ("scleroderma kidney") - atrophy and necrosis of the cortical
substance, mucoid and fibrinoid swelling in the walls of arteries and
arterioles, fibrinoid necrosis, sclerosis and hyalinosis.
43
Dystrophic и atrophic changes tubules,

thickening and sclerosis of the cerebral layer stroma.
Chronic renal failure (scleroderma renalis, nephrosclerosis)
Chronic heart insufficiency (scleroderma heart,
cardiosclerosis)
► OTHER SYSTEMIC CONNECTIVE

TISSUE DISEASES◄
The following is a brief characterization of other systemic
connective tissue diseases:
⮚ Periarteritis nodosa (Kussmaul-Meyer disease). Most often develops
in boys. The arterial walls of the arteries become
nodules of progressive sclerosis with narrowing of their lumen. In 90-
100% of cases renal arteries are affected, which is combined with
glomerulonephritis. In 80-90% of cases heart arteries are affected, in
57-60% - mesenteric arteries. Death can occur from renal failure,
myocardial infarction, gangrene of the intestine.
⮚ Dermatomyositis is a severe, progressive systemic disease of
connective tissue, skeletal and smooth tissue
musculature with impairment of its motor function, skin in the form of
erythema and edema of vessels of the microcirculatory channel with
damage to internal organs, often complicated by calcinosis and
purulent infection. Morphologic changes are inflammatory, dystrophic
and sclerotic in nature.
⮚ Ankylosing spondylitis (Bekhterev's disease) is a chronic systemic
joint disease with
predominant localization of the process in the sacroiliac joints, spinal
joints and paravertebral soft tissues. Destructive and inflammatory
changes in the tissues of small joints of the spine and intervertebral
discs (almost identical to the changes observed in rheumatoid arthritis)
with the outcome in ankylosis of the spinal column are characteristic.
Visceral manifestations include lesions of the aorta, heart, lungs, and
other organs. Amyloidosis with predominant kidney damage may
develop.
⮚ Sjögren's disease is a systemic autoimmune disease characterized by
chronic inflammation of exocrine
glands (primarily salivary and lacrimal glands) with a progressive
44
development of their secretory insufficiency in combination with

various systemic manifestations. The main and pathognomonic
morphological sign is lymphoplasmacytic infiltration of the
parenchyma of exocrine glands. In many cases, this infiltration is
found in other organs and tissues, takes a generalized character with
involvement of muscles (myositis), gastrointestinal tract (pancreatitis
and atrophic gastritis), lungs (lymphocytic interstitial pneumonitis),
kidneys (interstitial nephritis), vessels (peripheral vasculitis) and
others.
45
SECTION III
RESPIRATORY DISEASES
The peculiarity of lung structure, age features and a large number of

etiological factors characterize the diversity of clinical and morphological
manifestations of respiratory diseases.
Among the respiratory diseases, the most important are:
• pneumonia;
• Destructive lung diseases (abscess, gangrene);
• chronic diseases of the lower respiratory tract;
• other lung diseases (tumors, malformations). Also, there
are acute and chronic diseases.
ACUTE DISEASES
► ACUTE BRONCHITIS◄
Acute bronchitis is an acute diffuse inflammation of the
bronchial mucosa. It can be an independent disease or a
manifestation of a number of diseases, in particular pneumonia,
chronic glomerulonephritis with renal failure (acute uremic
bronchitis) and others.
Acute bronchitis tends to be more severe in children. Clinically,
acute bronchitis is manifested by cough, dyspnea and tachypnea.
ETHIOLOGY
• viruses, especially respiratory syncytial virus (RS virus);
• bacteria, most commonly Haemophilus influenzae and Streptococcus
pneumoniae;
• exposure to chemical agents in the inhaled air (cigarette smoke,
sulfur dioxide and chlorine vapors, nitrogen oxides);
• exposure to physical agents (dry or cold air, radiation);
• exposure to dust (household and industrial dust in increased
concentration).
PATHOGENESIS.
Several factors underlie the pathogenesis of acute bronchitis:
46
• impaired function of the local bronchopulmonary defense system

(d e c r e a s e d function of the mesenteric epithelium, decreased
activity of antitrypsin, decreased production of surfactant, lysozyme,
interferon, protective IgA, decreased function of T-lymphocytes,
alveolar macrophages);
• the development of the classic pathogenetic triad:
- Hypercrinia (hyperfunctioning of bronchial mucous glands,
hyperproduction of mucus);
- dyscrinia (increased viscosity of sputum due to changes in its
physicochemical properties and a decrease in its rheology);
- mucostasis (stagnation of viscous, thick sputum in the bronchi);
• favorable conditions for the introduction of infectious agents into the
bronchi as a result of the above factors.
The following is a classification of acute bronchitis (see Figure 15).
Figure 15: Classification of acute bronchitis.
PATHOLOGIC ANATOMY AND MORPHOGENESIS

mucous membrane mucous membrane of the
bronchi full of blood, swollen, there may be
small hemorrhages, ulceration. In the lumen
bronchi a lot of mucus. The bronchial mucosa is developing
various forms catarrh (serous,
47
mucous, purulent, mixed), fibrinous or fibrinous-hemorrhagic

inflammation; destruction of the bronchial wall is possible,
sometimes with ulceration of its mucosa (destructive-
ulcerative bronchitis). Lympho-leukocytic infiltration of the
bronchial wall and
peribronchial lung tissue.
Complications are often associated with impaired drainage function of
the bronchi, which contributes to aspiration of infected mucus into the distal
parts of the bronchial tree and the development of inflammation of lung
tissue (bronchopneumonia). In panbronchitis, inflammation may s p r e a d to
the lung tissue (peribronchial interstitial pneumonia).
The outcome depends on the depth of damage to the bronchial wall.
Serous and mucous bronchial catarrhs are reversible. Destruction of the
bronchial wall (purulent catarrh, destructive bronchitis) contributes to the
development of pneumonia. With prolonged exposure to a pathogenic factor
- transition to chronic bronchitis.
► BRONCHIOLITIS◄
Bronchiolitis is an acute inflammation of the bronchioles.
Currently, there is no unified and generally accepted

pathomorphologic classification of bronchiolitis. Nevertheless, based on
several criteria, they are distinguished:
• Depending on the etiology:

- postinfectious - acute bronchiolitis caused by respiratory syncytial
virus, adenovirus, parainfluenza virus, Mycoplasma pneumoniae;
- Inhalation - caused by gases (CO, SO2 , NO2 , O3 ), acid vapors,
organic and inorganic dust, smoking;
- drug-induced - penicillins, amiodarone, cephalosporins, etc;
- idiopathic - combined or not combined with other diseases (collagen
diseases, idiopathic pulmonary fibrosis, adult respiratory distress
syndrome, etc.);
- Bronchiolitis obliterans - HIV infection, herpes virus,
cytomegalovirus, aspergillus, legionella, etc.
48
• By type of inflammation:
- exudative bronchiolitis (acute) - fibrinous, necrotizing, etc.;
- Productive-sclerotic bronchiolitis (chronic) - respiratory, follicular,
diffuse panbronchiolitis, etc.
PATHOLOGICAL ANATOMY
Acute bronchiolitis is manifested by necrosis of the epithelium
with and without basal membrane lesions. The cellular
infiltrate is dominated by polymorphonuclear leukocytes or
lymphocytes (usually predominant in viral infection). In case
of pseudomembranous (fibrinous) inflammation - there are
deposits of fibrin and cellular detritus on the surface of
bronchioles. Fibrin accumulates under the basal membrane
around capillaries.
Complications:
• going chronic;
• secondary infection;
• increased risk of developing COPD and asthma;
• the development of severe respiratory failure.
Outcome. Acute bronchiolitis can resolve on its own, without special
pathogenetic therapy. In the next five years after acute bronchiolitis,
bronchial hyperresponsiveness and a high risk of bronchial asthma
development persist.
► PNEUMONIA◄
Pneumonia is an acute inflammation of the lung tissue, usually,
of infectious origin with
predominantly lesions of the alveoli and interstitial
lung tissue.
Pneumonia is characterized by the accumulation of exudate in the

cavity formations of the lungs (alveoli, bronchioles, bronchi) and/or cellular
infiltrate in the interstitial tissue (interalveolar septa, interlobular layers,
peribronchial and perivascular tissue).
49
ETHIOLOGY
The etiology of pneumonias is diverse, but more often their occurrence
is associated with infectious agents. In addition to infection (especially viral)
of the upper respiratory tract, the following risk factors for pneumonia are
identified:
• bronchial tree obstruction;
• immunodeficiency conditions;
• alcohol;
• smoking;
• inhalation of toxic substances;
• traumatic injury;
• impaired pulmonary hemodynamics;
• postoperative period and massive infusion therapy;
• malignant tumors;
• stress (hypothermia, emotional overstrain).
PATHOGENESIS.
Schematically, the pathogenesis is summarized in Figure 16.
Figure 16. Scheme of the pathogenesis of pneumonia.
CLASSIFICATION
Etiology: By distribution: Pathogenesis:

• bacterial; • one-sided; • primary;
• viral; • double-sided; • secondary.
• ornithous; • acinar;
• rickettsial; • miliary;
• mycoplasma; • focal plumage;
50
• fungal; • segmental;
• mixed; • Polysegmental;
• allergic; • equity;
• unspecified • total.
etiology
By clinical and Severity: Downstream:
morphologic features: • extremely severe; • sharp;
• parenchymatous • heavy; • protracted.
(croupy); • medium
• interstitial; severity
• bronchopneumonia. ;
• lungs;
• abortifacient.
Primary pneumonia includes pneumonia as an independent disease
and as a manifestation of another disease with nosologic specificity (e.g.,
influenza, plague pneumonia).
Secondary pneumonias are most often a complication of diseases
(aspiration, hypostatic, postoperative, against the background of
exacerbation of CNSL, septic, immunodeficiency, traumatic, contact, toxic,
thermal).
Of the acute pneumonias, croup pneumonia, bronchopneumonia and interstitial

pneumonia are the most important clinically.
VALVULAR PNEUMONIA
Lobular (croupy) pneumonia - an acute infectious and allergic

disease in which one or more lobes of the lung are affected,
fibrinous exudate is detected in the alveoli, and on the pleura -
fibrinous deposits.
ETHIOLOGY
The most frequent causative agents are pneumococci types I, II, III and
IV, Klebsiella. Pneumococcal pneumonia is most common in initially healthy
people aged 20 to 50 years, whereas Klebsiella pneumonia usually occurs in
the elderly and debilitated.
MORPHOGENESIS AND PATHOLOGIC ANATOMY

Classically, croup pneumonia runs in 4 stages:
• tidal stage (1st day);
51
• stage of red stupor (2-4 days);

• gray stupor stage (4-6 days);
• resolution stage (9-11 days).
The affected lung lobe is enlarged, dense, dark
red in color, homogeneous, smooth on the
section, bloody fluid flows when pressing. Pleura
is dull.
Stage I - tidal
stage Microcirculatory vessels are dilated, stasis and
hyperemia. Alveolar cavities are filled with
serous exudate, cells of alveolar epithelium and
blood elements (serous or serous-hemorrhagic
inflammation).
The affected lung lobe is enlarged, dense, pleura

has the appearance of "fogged glass". The surface
Stage II - of the lobe section is homogeneous, red, dry,
the stage of granular.
red cecum. The lumen of the alveoli is dilated. A network of
fibrin containing erythrocytes and a smaller
number of leukocytes is visible in the distended
alveoli.
The lung lobe is sharply enlarged, dense, gray in
color. Pleura is covered with fibrin films.
Stage III -
stage III -
stage III - In the lumen of the alveoli - fibrin threads and
gray stupor. neutrophils. The number of erythrocytes in the
alveolar lumen decreases due to hemolysis.
The lung lobe is enlarged, softer than in the

stages of senescence, the surface of the incision is
moist, yellowish-gray in color, turbid fluid flows
Stage IV - out when pressing.
resolution
stage Fibrinous exudate in the lumen of the alveoli and
fibrin deposits on the pleura are resorbed. In the
lumen of the alveoli residual infiltration with
neutrophils.
52
Distinguish pulmonary and extrapulmonary complications of croup
pneumonia:
• pulmonary complications:
- carnification of the lung (due to insufficient fibrinolytic
function of neutrophils, the fibrin masses in the alveoli
undergo organization);
- an acute abscess;
- gangrene of the lung;
- pleural empyema.
• extrapulmonary complications:
- lymphogenic generalization (purulent mediastinitis,
purulent pericarditis);
- hematogenous generalization (metastatic abscesses in the
brain, purulent meningitis, acute polyposis- ulcerative
endocarditis, etc.).
Death may result from pulmonary and cardiac failure or purulent and
obstructive complications.
53
Fig. 17. Schematic representation of changes in lobular (croupy)

pneumonia.
54
BRONCHOPNEUMONIA
Bronchopneumonia (focal pneumonia) is characterized by the

development of foci of acute inflammation with sizes from acinus
to segment and more. In this case, the inflammatory process
begins in the bronchi.
A distinctive pathomorphologic feature of focal pneumonia is a focus of

inflammation with bronchitis and/or bronchiolitis. Disruption of the drainage
function of the bronchi leads to the penetration of infection into the respiratory
parts of the lungs, in their lumen accumulates exudate, the nature of which has
some relationship with the nature of the pathogen. Inflammation more often
spreads to the lung tissue intrabronchially (descending pathway, usually in
catarrhal bronchitis or bronchiolitis), less often peribronchially (usually in
destructive bronchitis or bronchiolitis).
ETHIOLOGY
• usually caused by microorganisms (staphylococci, streptococci,
Haemophilus influenzae, Escherichia coli and fungi);
• septicemia and toxinemia often develop, manifested by fever and impaired
consciousness;
• Bronchopneumonia also develops under the influence of chemical and
physical factors, which allows us to distinguish uremic, lipid, dust,
radiation pneumonia and others.
Foci of inflammation may be of different sizes, dense, grayish-
red on the section. Depending on the size of the foci, a
distinction is made between miliary (alveolitis), acinusic,
lobular,
confluent lobular, segmental and polisegmental
bronchopneumonia.
Bronchial mucosa is full blooded and edematous.

Hypersecretion of mucus by glands and bocaloid cells. The
covering prismatic epithelium is sloughing. The walls of
bronchi and bronchioles thicken due to edema and cellular
infiltration. In the alveoli accumulations of exudate with an
admixture of mucus, many neutrophils, macrophages,
erythrocytes, descended alveolar epithelium; sometimes a small
amount of fibrin is determined. In the interalveolar septa -
cellular infiltrate.
55
PATHOMORPHOLOGIC FEATURES OF DIFFERENT ETIOLOGIC

VARIANTS OF PNEUMONIAS
Pneumococcal • in the foci of inflammation is dominated by

pneumonia fibrinous exudate, on the periphery of edema with
proliferating pathogen.
Staphylococcus • are often complicated by pulmonary destruction.
pneumoniae Sometimes ulcerative lesions of the bronchi (purulent-
necrotic bronchitis) appear. It develops as multifocal
bronchopneumonia with formation of peribronchial
abscesses;
• Hospital staphylococcal pneumonias can take a
septic course (bacteremia in 40% of patients), often
complicated by pleurisy;
• Macroscopically: multiple foci of gray or red
color of different sizes with yellowish-gray areas of
melting in the
center.
Streptococcus • usually occurs as a result of autoflora activation,

pneumoniae the route of infection is bronchogenic;
• is characterized by earlier involvement of lymph
nodes;
• pronounced interstitial component, often there
are areas of hemorrhagic necrosis, often complicated
by pleurisy;
• tendency to develop intrapulmonary (abscesses)
and extrapulmonary complications (otitis media,
lymphadenitis, less often metastatic lesions).
bones, joints, kidneys).
Fungal • is more commonly caused by fungi of the genus
pneumonia Candida;
• is characterized by a combination of exudative
purulent inflammation and productive granulomatous
inflammation, with exudate and in the
granulomas can show elements of the fungus.
Viral • interstitial inflammation, the exudate includes
pneumonia lymphocytes, macrophages and plasma cells;
• in the lumen of alveoli and bronchioles - a large
number of hyaline membranes formed from fibrinous
exudate. The lumen of the alveoli
is often left vacant;
56
• Influenza virus can cause acute lightning-quick

hemorrhagic pneumonia, which can lead to rapid
death.
of the body.
Pneumonias in • most most frequent causative
immunodeficient agent of opportunistic pneumonias: Pneumocystis
people carinii, viruses (cytomegalovirus, measles virus).
• The alveoli are filled with frothy pink exudate,
and rounded or semilunar microorganisms may be
detected;
• in infection,
cytomegalovirus infection, characteristic
intranuclear inclusions may be observed;
• In measles pneumonia, giant cells form
peribronchially, and squamous cell metaplasia is also
observed
of the bronchial epithelium and bronchioles.
Legionnaires' • the causative agent is Legionella pneumophilia;
disease • The inflammation is localized in the alveoli and
terminal bronchioles and is associated with the
corresponding bronchus;
• primary inflammation involves the vessel walls,
which creates conditions for microthrombosis;
• Infiltrates adjacent to the pleura may resemble a
pulmonary infarction.
Non-infectious pneumonias
Aspiration • develops when fluid or food is aspirated into the
pneumonia lungs, leading to the development of secondary
pneumonia;
• localization of the lesion depends on the
patient's position in bed: when the patient is on the
back, the apical segment of the lower lobe is most
often affected, when the patient is on the right side -
the posterior segment of the upper lobe;
• If anaerobic microorganisms are present, lung
abscesses may form.
Lipid • Endogenous lipid pneumonia develops with
pneumonia airway obstruction and is manifested by the
accumulation of macrophages with frothy cytoplasm
and giant cells in the exudate;
• exogenous lipid pneumonia occurs in
57
as a result of aspiration with lipid-containing

materials, such as liquid paraffin or oil nasal drops.
The lipid vacuoles are engulfed by the giant cells of
foreign
tel.
Eosinophilic • The presence of a large number of eosinophils
pneumonia in the interstitial tissue and alveoli;
• inflammation may lead to destruction of the
wall of bronchioles and bronchioles with replacement
by granulomatous tissue and giant cells;
• eosinophilic pneumonia may
occur when parasites migrate through lung tissue, or
may be idiopathic.
Complications. Complications of bronchopneumonia depend on the
etiology, age and general condition of the patient. Carnification or
suppuration of the focus of inflammation with abscess formation may occur.
Death of patients may be due to suppuration of the lung, purulent pleurisy.
INTERSTITIAL (INTERSTITIAL) PNEUMONIA

Interstitial (interstitial) pneumonia
is characterized by the development of inflammation in the
interstitial tissue (stroma) of the lung.
In interstitial pneumonia (alveolitis), inflammation primarily occurs in
the interalveolar and peribronchial stroma, in the lumen of alveoli and
bronchioles secondary exudative manifestations are possible.
ETHIOPATOGENESIS
Among the causative factors of interstitial pneumonia, viruses,
mycoplasmas, fungi, and pneumocysts are of leading importance.
In the pathogenesis of interstitial pneumonia the main significance is
the damage of alveolocytes, endothelium of vessels of the microcirculatory
channel by the pathogen, which leads to the development of inflammation,
sometimes with the participation of immunopathologic mechanisms by the
type of reactions HNT and HZT.
Macroscopically, the lungs are characterized by reduced airiness
and elasticity.
58
Microscopically, damage and regeneration of alveolocytes,

capillary hemorrhage, polymorphonuclear cell infiltration of
interstitial tissue, protein effusion with single leukocytes and
macrophages accumulates in alveoli, often hyaline membranes
are formed. The outcome may be
interstitial fibrosis.
Depending on the features of localization of the inflammatory process

in the interstitial tissue of the lung distinguish 3 forms of interstitial
pneumonia:
• peribronchial pneumonia - usually occurs as a manifestation of
respiratory viral infections or as a complication of measles. The
inflammatory process, having started in the bronchial wall
(panbronchitis), proceeds to the peribronchial tissue and spreads to the
adjacent interalveolar septa. Inflammatory infiltration of the
interalveolar septa leads to their thickening. Exudate with a large
number of alveolar macrophages, single neutrophils accumulates in the
alveoli;
• Interlobular pneumonia - occurs when inflammation, usually caused
by streptococcus or staphylococcus, spreads to the interlobular septa.
Sometimes it takes the character of phlegmonous inflammation and is
accompanied by melting of interlobular septa (stratifying or
sequestering interstitial pneumonia).
• interalveolar (interstitial) pneumonia - occupies a special place
among interstitial pneumonias by its etiology, pathogenesis and
morphological manifestations. In chronic course, interalveolar
(interstitial) pneumonia can be a morphologic basis of a group of
diseases, which are called interstitial lung diseases.
ACUTE DESTRUCTIVE PROCESSES IN THE LUNGS

Acute destructive processes in the lungs include abscess and gangrene
of the lung.
► ABSCESS OF THE LUNG◄
Abscess of the lung - limited purulent

inflammation in the lung tissue.
59
Depending on the origin, lung abscess can be pneumoniogenic and

bronchogenic, and can be acute and chronic.
Pneumoniogenic lung abscess occurs as a complication of
pneumonia of any etiology, usually staphylococcal and streptococcal.
Bronchogenic lung abscess occurs when the wall of the bronchiectasis
is destroyed and inflammation passes to the neighboring lung tissue with the
subsequent development of necrosis, suppuration and the formation of a cavity
- abscess.
A cavity filled with a viscous exudate of yellow-green color

(pus).
One or many zones of leukocytic infiltration, exudation,

necrosis of lung tissue. As a result of infection of necrotic
masses, a cavity(s) containing pus is formed. The inflammatory
focus is initially limited by a granulation shaft, then connective
tissue and fibrous capsule (chronic abscess). The outer layers of
the capsule are represented by connective tissue, the inner -
granulation tissue and pus (pyogenic membrane). Along the
course of lymphatic outflow from the wall of the chronic
abscess to the lung root, whitish layers of connective tissue
appear, which leads to fibrosis and deformity
of the lung tissue.
Complications:
• purulent pleurisy, pleural empyema, pyopneumothorax;
- bronchiectasis;
- purulent melting of the vessel walls with pulmonary hemorrhage;
- lymphogenic / hematogenous spread infections
(formation of metastatic abscesses in other organs, septicopoiesis);
• Amyloidosis (in chronic abscesses).
Outcomes:
• going chronic;
• organization (scarring).
60
► GANGRENE OF THE LUNG.
Gangrene of the lung is a widespread progressive purulent-

rotting process in the lung tissue with the formation of
sequestrations and cavities, without a limiting capsule.
ETHIOLOGY
The main causes of lung gangrene include decreased immunologic
reactivity of the organism, impaired pulmonary circulation and bronchial
patency in combination with infection of the respiratory tract with aerobic
microbial flora. The main predisposing factors include chronic alcohol
intoxication, chronic inflammatory diseases of the respiratory system,
advanced age.
CLASSIFICATION
By mechanism of development:
• post-pneumonic;
• obturation;
• aspiration (bronchogenic);
• hematogenous;
• lymphogenic;
• post-traumatic;
• thromboembolic;
By lung tissue involvement:
• subtotal;
• shared;
• total;
• double-sided.
The absence of restriction of the altered lung tissue from the

healthy one is characteristic. The area of gangrenous tissue
without sharp boundaries passes into softened lung tissue of
dark color, which also without clear boundaries passes into
healthy tissue. A large amount of stinky, frothy sputum, which
has the appearance of "meat slop" (due to the admixture of
blood). The process usually involves the pleura, which leads to
the development of a putrefactive empyema, or
pyopneumothorax.
61
Leukocytic infiltration, fibrinous impregnation of the alveolar

septa, their swelling и loss
Structuralism.
CHRONIC NONSPECIFIC LUNG DISEASES (CNLD)

Chronic nonspecific lung diseases - a group of lung diseases of
different etiology, pathogenesis and morphology, which are
characterized by the development of chronic cough with sputum
production and paroxysmal or constant difficulty breathing,
which is not associated with specific infectious diseases.
According to functional and morphologic features, lesions of their air-

conducting or respiratory compartments are subdivided into three groups:
• obstructive;
• restrictive;
• mixed - obstructive with restrictive disorders or restrictive with
obstructive disorders.
The combination of restriction with obstruction is seen in the late

stages of virtually all chronic diffuse lung diseases.
Chronic bronchitis, bronchial asthma, bronchiectatic disease, chronic
obstructive pulmonary emphysema, chronic abscess, chronic pneumonia, and
interstitial lung disease are included in the CNSL group.
Small circulatory circle hypertension and pulmonary heart disease
develop in all CLL.
Chronic obstructive pulmonary diseases are diseases of the

airways characterized by increased resistance to air passage due
to partial or complete obstruction at any level (from the trachea
to the respiratory bronchioles), other than bronchial asthma.
Obstructive diseases include the following diseases: chronic

obstructive bronchitis, chronic obstructive pulmonary emphysema,
bronchiectatic disease, chronic bronchiolitis. The basis of obstructive lung
diseases is a violation of drainage
62
bronchial function, which is the main cause of bronchial obstruction. In

recent years, the group concept of "obstructive lung disease" is widely used
in relation to the group of chronic obstructive diseases.
Restrictive lung diseases are characterized by a decrease in the

volume of lung parenchyma with a decrease in the vital capacity
of the lungs. This group includes interstitial lung diseases.
The basis of restrictive lung diseases is the development of

inflammation and fibrosis in the interstitium of respiratory lung sections,
often on an immune basis, leading to interstitial fibrosis and block of the
aerohematic barrier, which is accompanied by clinical symptoms of
progressive respiratory failure. Most lung diseases in the late stages of
development have, as a rule, both obstructive and restrictive components.
ETHIOPATOGENESIS
The following mechanisms underlie the pathogenesis and morphogenesis of
CNPL (see Figure 18):
• bronchitogenic;
• pneumoniogenic;
• pneumonitogenic.
Bronchitogenic The basis is a violation of bronchial drainage

mechanism function and bronchial patency. Diseases united by
this mechanism (chronic obstructive pulmonary
diseases) are represented by chronic bronchitis,
bronchiectatic disease, chronic obstructive
emphysema, chronic bronchitis, bronchitis,
bronchitis, bronchitis, bronchitis, and bronchitis.
emphysema lungs,
bronchial asthma.
Pneumoniogenic Associated with acute pneumonia and its
mechanism complications (lung abscess, carnification).
Pneumonitogenic Defines the development of chronic
mechanism interstitial diseases represented by various forms of
"fibrosing alveolitis" or pneumonitis.
63
Fig. 18: Scheme of the pathogenesis of CLL.
In the outcome of all three mechanisms of the disease, there is a

reorganization of pulmonary tissue with the development of secondary
pulmonary hypertension, leading to hypertrophy of the right ventricle of the
heart and increasing pulmonary-cardiac failure.
► CHRONIC BRONCHITIS◄
Chronic bronchitis - chronic inflammation of the bronchi

resulting from prolonged acute bronchitis or prolonged exposure
of the bronchial mucosa to bacteria o r viruses, physical and
chemical factors.
Chronic bronchitis is diagnosed when a patient has a productive cough

for two consecutive years for at least three months of the year.
64
ETHIOPATOGENESIS
Etiologic factors in the initial onset and subsequent exacerbation of chronic

bronchitis:
• infectious factors;
• climatic and weather factors;
• polutants of industrial and other origin;
• Tobacco smoke (from active and passive smoking), etc.
Figure 19: Scheme of pathogenesis of chronic bronchitis.

65
CLASSIFICATION
Figure 20: Classification of chronic bronchitis.
Bronchial walls are thickened, surrounded by layers of gray

heavy tissue (peribronchial sclerosis). On the lung section,
bronchial walls protrude above the section surface (like "goose
feathers"), the walls are sometimes deformed and often with the
presence of dilatations
(bronchiectasis).
Changes in the bronchial wall in chronic bronchitis are diverse

and depend on the nature of inflammation, the depth of the
lesion, the caliber of the bronchioles, the etiology and duration
of the disease.
• catarrhal bronchitis - loose infiltration of bronchial
mucosa with histiocytes, lymphocytes, plasma cells.
Hemorrhage and edema of the mucosa. Hypersecretion
of mucus. Metaplasia of the epithelium into multilayer
squamous, increase in the number and size of bocaloid
cells, dilation of mucous glands and excretory ducts.
• purulent bronchitis - diffuse infiltration with
66
with an admixture of leukocytes. The basal membrane is

thickened, there are phenomena of hypersecretion and
metaplasia in the epithelium. In the lumen of bronchi
purulent exudate.
• destructive bronchitis - diffuse infiltration of all layers of
the bronchial wall with histiocytes, lymphocytes and
plasma cells. In places, cellular infiltration turns into
granulation tissue replacing the bronchial wall, with
subsequent sclerosis. The mucous membrane is
thickened, forms polypous outgrowths
(destructive-polyposis bronchitis) or ulcerated
(destructive-ulcerative bronchitis).
Figure 21: Schematic representation of changes in chronic bronchitis.
Complications:
• pulmonary hypertension, pulmonary heart, pulmonary heart
failure;
• dysplasia of bronchial epithelium with subsequent malignant
transformation;
• amyloidosis of the kidneys and other organs;
• bronchiectasis.
67
► BRONCHOECTASES◄.
Bronchiectasis is a persistent dilatation of the bronchial lumen

with impaired drainage function and accumulation of mucous
membrane secretion in the dilated part. If the clinical and
morphological picture is dominated by bronchial dilatation, we
speak of bronchiectatic disease.
CLASSIFICATION
By origin: By distribution: Form:
• primary • one-sided; • cylindrical;
(congenital); • bilateral • baggy;
• secondary • spindly;
• cystic;
• mixed
By the numbers: Severity: Downstream:
• singles; • light; • bronchitic stage;
• multiple • of • stage of marked
medium clinical changes;
severity; • stage of
• heavy; complications
• heavy
complicated
form.
ETHIOPATOGENESIS
Congenital bronchiectasis is the result of improper formation of the
bronchial tree and can be type I (large or medium bronchus blindly ends
without division into small bronchi and acini), or type II (large or medium
bronchus without division into small bronchi passes into bronchioles and
acini).
Acquired bronchiectasis is a consequence, as a rule, of chronic
bronchitis due to bulging of the bronchial wall, in the place of the most
pronounced inflammatory process, more often at coughing thrusts.
In addition, the following bronchiectasis is distinguished:
• post-infectious (in tuberculosis, adenovirus infection, measles, etc.);
• obstructive (if in the presence of foreign body
в bronchi, tumors, mucous plugs, etc.);
• pollutant (due to action external chemical
factors);
68
• aspiration (due to aspiration gastric

contents and other foreign bodies);
• hereditary developmental anomalies (cystic fibrosis, congenital
dyskinesia of the ciliated epithelium);
• congenital anomalies (intrapulmonary sequestration,
congenital bronchiectasis);
• bronchiectasis in immune disorders
(hypogammaglobulinemia, etc.);
• Bronchiectasis in McLeod and Swire-James syndromes;
• idiopathic bronchiectasis.
Bronchiectasis can be saccular (at the level of proximal
bronchi, including bronchi of the 4th order), cylindrical (at the
level of bronchi of the 6th-10th order) or spindle-shaped.
Bronchiectasis appear in the focus of unresolved pneumonia, in
areas of atelectasis and
collapse (collapse of the respiratory structures of the lung).
In the bronchiectasis cavity there is purulent exudate containing

microbial bodies and sloughed epithelium. The covering
epithelium is represented by denuded basal cells, foci of
polyposis and squamous cell metaplasia. The basal membrane
is hyalinized, corrugated. Dystrophy and destruction of
bronchus cartilaginous lamina, atrophy and destruction of
muscular and elastic layers, sclerosis and diffuse histiocytic and
lymphocytic inflammatory infiltration of all layers of
bronchiectasis wall with admixture of polymorphonuclear
leukocytes. In the adjacent pulmonary parenchyma one can see
fibrosis fields and foci of obstructive pulmonary emphysema.
Complications:
• pulmonary hemorrhage;
• Lung abscesses (bronchiectatic abscesses);
• pneumonia;
• sepsis;
• pleural empyema;
• chronic cardiopulmonary failure;
• Secondary systemic amyloidosis (AA-amyloidosis).
69
► EMPHYSEMA LUNG◄
Lung emphysema (from Greek emphysao - to bloat) - a

disease of the respiratory tract, characterized by pathological
expansion of air spaces of distal bronchioles, which is
accompanied by destructive-morphological changes in alveolar
walls.
ETHIOPATOGENESIS
There are two groups of factors that lead to the development of
pulmonary emphysema:
• factors that violate the elasticity and strength of elements of the lung
structure (lead to the development of primary, diffuse pulmonary
emphysema):
-microcirculation disorders;
-Changes in surfactant properties;
-congenital alpha-1-antitrypsin deficiency;
-gaseous substances (cadmium compounds, nitrogen oxides, etc.);
-tobacco smoke;
-dust particles in the inhaled air;
• factors that increase the pressure in the respiratory lung and
increase the stretching of the alveoli (leading to the development of
secondary, obstructive pulmonary emphysema):
- airway obstruction (e.g., chronic obstructive bronchitis).
The pathogenesis of emphysema is based on damage to the elastic
framework of the lungs due to the activation of leukocyte proteases
(elastase). Deficiency of serum antiproteases (α-1-antitrypsin) plays an
important role. In conditions of failure of the elastic stroma of the lung, the
so-called valve (valve) mechanism is activated: air passes into the alveoli at
the inlet, but does not leave at the outlet. Air accumulates in the acinus,
expands their cavities.
70
Figure 22. "Vicious circles" in the pathogenesis of emphysema.
CLASSIFICATION
By origin: Morphologically: Special Forms:
• primary • panacinar • congenital
; (panlobular); lobular
• Secondary • centrilobular; emphysema;
(due to other • periacinar • McLeod
diseases) (paraseptal); syndrome
• irregular (near
scar);
• bullous;
• mixed
By Downstream: Severity:
prevalence: • slowly progressing; • initial
• diffuse; • rapidly progressive; emphysem
• localized • form with frequent a;
recurrent periods of • pronounced;
decompensation or • heavy
exacerbation of
pulmonary
infections.
Several types of pulmonary emphysema are distinguished according to
morphological features (see Fig. 23).
71
Figure 23: Types of pulmonary emphysema.

Notes: TB - terminal bronchiole, RB - respiratory bronchiole, A - alveolus.
Centrolobular The air spaces in the center of the lobe (respiratory

bronchioles) are affected. It is most often localized in
the upper lobe. It is often combined with bronchiolitis
and chronic bronchitis.
Manacinar All airway cavities distal to the terminal bronchioles

(panlobular). are affected. The lower lobes of the lungs are usually
affected.
Maraseptal Peripheral areas of the lobules are affected, usually
adjacent to the pleura. Scarring of the affected tissue
is often observed.
Mixed Different parts of the lobule are affected. There is
almost always fibrosis of the affected lobules. It is
most often found around scars of tuberculous
etiology at the top of the lungs.
bullous Bullae (enlargements greater than 10 mm in
diameter) can occur in all four major types of
emphysema. Bullae often rupture, resulting in
spontaneous pneumothorax. Bullae are usually
located subpleurally.
72
A distinction is also made between compensatory (vicarious), senile

and interstitial emphysema:
• vicarious emphysema is an excessive inflation of the alveoli of
preserved lung tissue with loss of a significant volume of lung
parenchyma (e.g., unilateral pulmonectomy or lobectomy).
Destructive changes in the walls of the alveoli are absent;
• senile (senile) emphysema - caused by age-related changes in
lung tissue without destruction of elastic structures and alveolar
walls;
• Interstitial (interstitial) emphysema - characterized by air inflow
into the stroma of interalveolar septa at ruptures of alveolar walls
(due to prolonged coughing, in case of violation of ventilation).
From the root parts of the lungs, air can spread to the soft tissues
of the mediastinum and neck.
The lungs are enlarged in volume, after opening the pleural
cavities do not collapse, the anterior edges are rounded, go one
behind the other, may cover the mediastinal organs. On section
- porous appearance. Predominantly in the upper lobes under
the pleura are often seen large blisters from a few millimeters
to 1 cm or more in diameter (bullous emphysema). The lungs
are "crunchy" when felt.
Bronchi and bronchioles are diffusely dilated and their lumen is
detected with the naked eye.
The apertures of respiratory bronchioles and alveoli are dilated,

alveolar septa are thinned. Hypertrophy of smooth muscle
fibers of the closure plates, which have the appearance of club-
like thickenings. Thinning
and lysis of elastic fibers of the interalveolar septa.
Complications:
• respiratory failure;
• heart failure (cor pulmonale);
• pneumothorax (due to rupture of subpleural bullae).
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► BRONCHIAL ASTHMA◄
Bronchial asthma is a chronic inflammatory disease of the

respiratory tract with bronchial obstruction due to specific
immunologic or nonspecific mechanisms,
manifested by recurrent episodes of
wheezing, dyspnea and cough.
ETHIOPATHOGENESIS
Depending on the causes of bronchial asthma attacks:
• exogenous bronchial asthma - attacks are caused by exposure of the
respiratory tract to allergens from the external environment (plant
pollen, mold fungi, animal hair, microscopic mites of house dust). A
special variant is atopic bronchial asthma caused by hereditary
predisposition to allergic reactions;
• endogenous bronchial asthma - the attack is caused by such factors as
infection (bacterial or viral), physical activity, cold air, psycho-
emotional stimuli;
• bronchial asthma of mixed genesis - attacks may occur both when the
airways are exposed to an allergen and when the above factors are
present;
• Other forms of bronchial asthma - reflux-induced bronchial asthma,
aspirin-induced bronchial asthma, physical effort bronchial asthma,
occupational a s t h m a , etc.
A simplified scheme of the pathogenesis of bronchial asthma is
presented below in Figure 24.
The most typical morphological picture is characteristic for asthmatic
attack, while in the interictal period and against the background of therapy
the changes smooth out.
Lungs are enlarged, filling the whole thoracic cavity, rib
impressions are visible on the surface. The surface of lungs is
pale pink, on the section - gray-red. Moderate phenomena of
pneumosclerosis. Bronchial walls protrude above the cut
surface. Bronchial lumen is filled with dense grayish-yellow
casts of sputum.
The bronchial mucosa is hyperemic.
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In the dilated lumen of bronchi - mucous plugs, layers of

sloughed epithelium with admixture of neutrophils, eosinophils
and lymphocytes. Areas of basal membrane are denuded.
Charcot-Leiden crystals are revealed. The number of bocaloid
cells is increased. Diffuse infiltration of the wall, mainly by
eosinophils. Hypertrophy of bronchial muscular membrane and
phenomena
peribronchial sclerosis. Respiratory parts of lungs with
emphysematous changes.
Figure 24. Scheme of the pathogenesis of bronchial asthma.
Complications:
• asthmatic status - a severe, prolonged attack of suffocation,
which is difficult to control and requires specialized medical
care;
• Spontaneous pneumothorax - due to rupture of the lung due to a
sudden increase in pressure in it at the peak of the attack;
• collapse (collapse, atelectasis) of the lung;
• pneumonia;
• respiratory or pulmonary-cardiac failure.
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► INTERSTITIAL LUNG DISEASES LUNG◄
Interstitial lung diseases (ILD) are a heterogeneous group of

diseases characterized by primary in the interalveolar pulmonary
interstitium (pneumonitis) with the development of bilateral
diffuse pneumofibrosis.
ETHIOPATOGENESIS
According to the classification, there are 3 main forms of interstitial
lung disease:
• idiopathic fibrosing alveolitis - acts as a manifestation of other
diseases (systemic connective tissue diseases, viral hepatitis
[Hammen-Rich syndrome]);
• Exogenous allergic alveolitis - dust of household, plant or industrial
origin;
• toxic fibrosing alveolitis - antitumor antibiotics, antidiabetic,
cytostatic, immunosuppressive drugs, herbicides, mineral fertilizers,
etc.
The pathogenesis is based on disorders of immunologic homeostasis:

the development of the disease is associated with the appearance of
autoantigens with the formation of immune complexes and cellular
inflammatory reaction in the interstitium of the interalveolar septa.
MORPHOGENESIS, PATHOLOGIC ANATOMY.
There are 3 stages of morphologic changes in IBL:

Alveolitis stage
Infiltration of interstitial lung tissue with neutrophils,
lymphocytes, macrophages, plasma cells; in the lumen of
alveoli - serous exudate, often - hyaline membranes,
hyperplasia of alveolocytes of type II (diffuse alveolitis). In
some cases, the process has a focal character with the formation
of macrophagal
granulomas (granulomatous alveolitis).
Stage of disorganization of alveolar structures
Destruction of endothelium and basal membrane, increased
cellular infiltration в interstitium
with spreading inflammation to walls vessels и
perivascular tissue. Diffuse pneumofibrosis.
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Stage of cellular lung formation "Capillary block."

panacinar emphysema, bronchiectasis
(bronchioloectasis). Cysts with fibrous walls are formed, the
so-called "honeycomb lung" (resembles the
bee honeycomb).
Complications:
• pulmonary-cardiac failure;
• pulmonary hemorrhage;
• secondary amyloidosis;
• pneumoniogenic sepsis;
• asphyxia;
• acute respiratory failure;
• bronchopneumonia;
• air embolism.
► CANCER LUNG◄
Lung cancer is a malignant neoplasm of the lung

originating from bronchial epithelial tissue of various caliber.
ETHIOLOGY
• chemical carcinogens;
• chronic inflammatory processes leading to the development of
pneumosclerosis, chronic bronchitis, bronchiectasis;
• radioactive exposure;
• environmental pollution;
• occupational hazards;
• et al.
CLASSIFICATION
Classifications of lung cancer take into account: localization, nature of
growth, as well as macro- and microscopic picture. There are international
classification (according to TNM system), histological classification,
clinical-anatomical classification (according to the form and localization)
and others. The simplified histologic and clinical-anatomic classifications are
presented below.
HISTOLOGICAL CLASSIFICATION
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• Squamous cell (epidermoid) cancer

- highly differentiated;
-moderately differentiated;
- undifferentiated;
• Adenocarcinoma
- acinar;
- papillary;
- bronchoalveolar;
- solid;
- mixed;
• Small cell cancer
• Large cell cancer
• Mixed cancer
-squamous cell and adenocarcinoma;
-adenocarcinoma and small cell.
For clinical purposes, all epithelial malignant tumors of the lung are
divided into small cell cancer and non-small cell cancer (all other
histological types), which is due to the peculiarities of patient management
tactics.
• Small cell (20%);
• Non-small cell (80%):
-flat cell cancer (25-40%);
-adenocarcinoma (30-50%);
-large cell cancer (10-20%);
- glandular squamous cell;
- carcinoid;
-bronchial gland cancer;
-unclassifiable cancer.
CLINICO-ANATOMICAL CLASSIFICATION
• By localization:
- Central cancer originating from the trunk, lobe, and early
part of the segmental bronchus;
- Peripheral cancer originating from the peripheral segmental
bronchus and its branches, as well as from the alveolar
epithelium;
- mixed (massive).
• In the nature of growth:
- exophytic (endobronchial);
- Endophytic (exobronchial and peribronchial);
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• Form:
- plaque-like;
- polyposis;
-endobronchial diffuse;
- knotty;
- branched;
- knotty and branched.
• By the nature of the complications:
-metastases pulmonary and extrapulmonary;
-secondary pulmonary changes.
Central (root) lung cancer - develops in the mucosa of the main,
lobular and initial part of the segmental bronchus, initially in the form of a
small nodule (plaque). It is often complicated by segmental or lobular
atelectasis. Atelectasis leads to impaired drainage function of the bronchus,
the development of pneumonia, abscess, bronchiectasis, masking lung
cancer. At endophytic growth spreads to the mediastinal tissue, pericardium
and pleura. The histologic structure is predominantly squamous cell cancer
(against the background of previous squamous cell metaplasia of bronchial
epithelium).
Squamous cell cancer can be highly, moderately, and low-
differentiated:
• Highly differentiated cancer is characterized by keratin
formation and the formation of cancer pearls;
• for moderately differentiated cancer - mitoses and cell
polymorphism, some of which contain keratin;
• for low-differentiated squamous cell carcinoma - even
greater polymorphism of cells and nuclei (presence of
polygonal and spindle-shaped
cells), a large number of mitoses; keratin is determined
only in individual cells.
Peripheral cancer - arises in the mucosa of the peripheral mucosa of

the segmental bronchus, its smaller branches and bronchioles, rarely from
the alveolar epithelium. For a long time does not manifest clinically until it
reaches the pleura (pleurisy) or the main or segmental bronchus. By.
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histologic structure - predominantly glandular cancer.

(adenocarcinoma).
Glandular cancer (adenocarcinoma) can also have varying
degrees of differentiation:
• highly differentiated adenocarcinoma
consists of acinar, tubular or papillary structures whose
cells produce mucus;
• moderately differentiated adenocarcinoma has a
glandular-solid structure, it has a large large
number mitoses, mucus
formation is observed only in a part of cells;
• low-differentiated adenocarcinoma consists of solid
structures, its polygonal cells are able to produce mucus.
Features of small cell and large cell lung cancer.

• small cell cancer - consists of small lymphocyte-like or
"oat-like" cells with hyperchromic nuclei, the cells grow
in layers or strands; in some cases they have endocrine
activity.
• large cell carcinoma is represented by large polymorphic,
often giant
multinucleated cells that are unable to
to produce mucus.
Complications of lung cancer:
• metastases (equally can be considered a manifestation of tumor
progression) - cancer metastases, both lymphogenic and
hematogenous, are observed in 70% of cases. The first lymphogenic
metastases occur in peribronchial and bifurcation lymph nodes, then in
cervical lymph nodes and others. Among hematogenous metastases,
the most characteristic are metastases to the liver, brain, bones
(especially often to vertebrae) and adrenal glands. Root cancer more
often gives lymphogenic, peripheral cancer - hematogenous
metastases.
• secondary changes.
Patients die with the phenomena of progressive pulmonary-cardiac failure,
with the accession of pneumonia, the development of pulmonary
hemorrhage.
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SECTION IV.
GASTROINTESTINAL TRACT DISEASES
Diseases of the digestive tract organs are characterized by a variety of

their clinical and morphological features. They include independent primary
diseases, as well as other diseases (secondary), which are manifestations of a
number of diseases of infectious and non-infectious nature, acquired or
hereditary origin. These diseases may be based on various general
pathological processes such as alteration, inflammation, hyper- and
dysplastic processes, autoimmune disorders and, finally, tumors.
DISEASES OF THE PHARYNX AND PHARYNX
► TONSILLITIS (SORE THROAT)◄
Tonsillitis (sore throat) (from Latin angere: to choke) is an

infectious disease with marked inflammatory changes in the
lymphadenoid tissue of the pharynx and palatine tonsils.
ETHIOPATOGENESIS
The occurrence of tonsillitis is associated with a variety of pathogens
of bacterial, viral, fungal nature. However, the most significant are
staphylococci, streptococci, adenoviruses, as well as associations of
microorganisms.
• bacteria - most most common β-hemolytic
group A streptococcus, less frequently staphylococcus or
a combination of the two;
• viruses - more often adenoviruses (type 1-9), coxsackie enterovirus,
herpes virus;
• Vincennes spirochete in symbiosis with spindle bacillus (ulcerative
plaque sore throat);
• Candida fungi in symbiosis with pathologic cocci. Predisposing
factors:
- local and general hypothermia of the body;
- decrease in local and general immunity;
- trauma to the tonsils;
- nasal breathing disorder;
- chronic inflammatory processes in the o r a l cavity, nose and paranasal
sinuses.
81
CLASSIFICATION
The basic classification takes into account the division of tonsillitis
into acute and chronic and the different clinical and morphologic forms of
the disease (see Figure 25).
Figure 25: Clinical and morphologic forms of tonsillitis.
• Catarrhal sore throat - course

relatively The duration of the disease is 3-5 days.
The palatine tonsils are slightly enlarged, the mucous membrane
covering them and the edges of the palatine glands is
hyperemic. There are slightly enlarged and slightly painful
regional lymph nodes on the neck. The mucous membrane of
the palatine tonsils and palatine glands is sharply full-blooded
or bluish, dull, covered with mucus. Exudate serous or mucous-
leukocytic. Sometimes it lifts the epithelium and forms small
vesicles with turbid
with content.
• Fibrinous sore throat - most characteristic of diphtheria.

The tonsils are enlarged, on their surface - grayish-white plaque
in the form of a characteristic film. Inflammation may have a
croupy or diphtheritic character. In diphtheritic inflammation -
tonsils are e n l a r g e d ,
hyperemic, covered with dense films, at
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which are ulcerated. Lymph nodes

the neck is enlarged, and the fibers are swollen.
• Follicular and lacunar angina - the course of these forms of angina

is marked by a pronounced clinical picture, the duration of follicular
and lacunar angina - 5-7 days.
Lacunar sore throat - the process begins with the mucous
membrane of the lacunae: serous-mucous exudate accumulates
in the enlarged lacunae. Exudate protrudes from the mouths of
the lacunae in the form of whitish-yellowish plugs on the
surface of brightly hyperemic and enlarged tonsils.
Follicular sore throat - is characterized
by predominantly affected follicles. The tonsils are enlarged,
their mucous membrane is hyperemic, on the surface are
translucent in the form of yellow millet-shaped
of festering follicle dots.
Lacunar angina - ulceration of the epithelium of the lacunae,

infiltration of the mucosa with leukocytes, thrombosis of small
vessels and foci of purulent melting in the follicles.
Follicular sore throat - follicles with purulent melting, as well
as hyperplasic follicles with light centers. Small abscesses may
occur in the tonsil parenchyma when purulent-melting follicles
merge.
• Purulent sore throat - characterized by an increase in the size of the

tonsils due to swelling and infiltration of neutrophils. Purulent
inflammation is more often of a diffuse nature (phlegmonous s o r e
t h r o a t ), less often it is limited to a small area (tonsil abscess).
Possible transition of the purulent process to adjacent tissues and
dissemination of infection.
• Necrotic and gangrenous angina - characterized by superficial or

deep necrosis of the mucosa with the formation of defects with
irregular edges (necrotic-ulcerous angina). Not uncommon
hemorrhages in the mucous membrane of the pharynx and tonsils. In
gangrenous decay of tonsil tissue
83
they call it gangrenous angina. Necrotic and gangrenous angina are

observed most often in scarlatina, acute leukemia.
CHRONIC TONSILLITIS
In chronic tonsillitis, which develops as a result of repeated
recurrences (recurrent sore throat), there is hyperplasia and sclerosis of
lymphoid tissue of tonsils, sclerosis of the capsule, enlargement of lacunae,
ulceration of the epithelium. Sometimes there is a sharp hyperplasia of the
entire lymphoid apparatus of the pharynx and pharynx. Changes in the
pharynx and tonsils, both in acute and chronic sore throat, are accompanied
by hyperplasia of the tissue of lymph nodes of the neck.
Complications of tonsillitis:
• Local complications - associated with the transition of the
inflammatory process to the surrounding tissues: paratonsillar
(pharyngeal) abscess, phlegmonous inflammation of the pharyngeal
plaque, thrombophlebitis;
• General complications - sepsis, rheumatism, glomerulonephritis and
other infectious and allergic diseases.
DISEASES ESOPHAGUS
Among the diseases of the esophagus most most
common are diverticula, esophagitis, and tumors.
► DIVERTICULA ESOPHAGUS◄
An esophageal diverticulum is a limited blind bulge of the

esophageal wall that consists of all layers (true diverticulum) or
only the mucosal and submucosal layers bulging through gaps in
the muscular layer (muscular diverticulum).
Diverticula are rarely seen before the age of 30 and often after the age
of 50; males predominate. Diverticula are most commonly found in the
thoracic esophagus. The vast majority of diverticula are acquired; congenital
diverticula are extremely rare. When esophageal motility is impaired
(esophagospasm), pseudodiverticula are observed, which appear only at the
time of esophageal contraction; they disappear when the esophagus relaxes.
A distinction is made between pulsatile and traction diverticula:
84
• Pulsatile diverticula are formed due to bulging of the esophageal wall

under the effect of high intraesophageal pressure that occurs during
esophageal contraction;
• traction diverticula are associated with inflammatory process in the
surrounding tissues and scar formation, which pull the esophageal wall
towards the affected organ (mediastinal lymphadenitis, chronic
mediastinitis, pleurisy).
The traction mechanism is observed at the very beginning of the
diverticulum development, then pulsatile factors join, as a result of which the
diverticulum becomes mixed - pulsatile-tractile.
• inflammation in the wall of the diverticulum (diverticulitis) and
transfer to the surrounding tissues (peridiverticulitis);
• rupture of the diverticulum wall - development of peritonitis, purulent
mediastinitis, etc;
• malignization.
► EZOFAGIT◄.
Esophagitis is an inflammation of the mucous membrane of the esophagus.
ETHIOPATHOGENESIS
The following factors are the most common causes of esophagitis:
• Gastroesophageal reflux (gastroesophageal reflux disease [GERD]),
resulting in damage to the esophageal mucosa due to gastric juice
(reflux esophagitis);
• infections (Candida fungi, herpes simplex virus, cytomegalovirus) -
most often in immunosuppressed persons (AIDS, glucocorticoid
therapy, chemotherapy);
• chemical factors - chemical burns with alkali or acid, solvents, strong
oxidizers, ethyl alcohol;
• physical factors - against the background of radiation therapy,
traumatic impact of esophageal/gastric tube, etc.
CLASSIFICATION
The following is a classification of esophagitis, taking into account the
etiologic and clinical and morphologic forms of the disease (Fig. 26).
85
According to the course of the disease, a distinction is made between

acute and chronic esophagitis:
• acute esophagitis - occurs due to the impact on the esophageal mucosa
of hot food, chemicals (acids, alkalis, etc.), ionizing radiation, in acute
infectious diseases (scarlatina, diphtheria, etc.), acute pharyngitis and
gastritis;
• Chronic esophagitis - occurs due to repeated exposure of the
esophageal mucosa to various irritants - hot, spicy, coarse food,
alcohol, as well as some toxic substances. Chronic esophagitis can
also develop with stagnation and decomposition of food in the
esophagus in patients with stenosis or diverticulum of the esophagus,
often accompanies chronic inflammatory diseases or may be a
consequence of acute esophagitis. One of the most common causes is
GERD.
Figure 26: Classification of esophagitis.

86
• Catarrhal esophagitis is the most common form of acute esophagitis.
The esophageal mucosa is edematous and hyperemic;
• erosive esophagitis - the mucous membrane is hyperemic, numerous
erosions are defined on its surface. The surface of erosions is covered
with hemorrhagic exudate, pus, fibrinous plaque. There is edema and
leukocytic infiltration in submucosa and muscularis;
• Hemorrhagic esophagitis - hemorrhages predominate in the mucosa
and underlying layers;
• pseudomembranous esophagitis - on the surface of the mucosa
significant fibrin effusion, forming an easily removable film of gray-
yellow color;
• necrotic esophagitis - inflammatory infiltration and necrosis of the
mucosa and underlying layers of the esophageal wall with formation
of deep ulcers and rejection of necrotic masses. On the surface of the
mucosa - bloody and purulent discharge;
• chronic esophagitis - manifested by hyperemia, edema, infiltration of
the esophageal mucosa. The surface of the mucosa is covered with
thick viscous mucus, erosions, ulcers and leukoplakia are revealed.
There are dystrophic changes of epithelium, gland atrophy, fibrosis in
the underlying layers.
The outcome of esophagitis depends on the severity, duration and
morphologic type of the disease. One of the outcomes is connective tissue
overgrowth in the esophageal wall and its scarring.
Complications:
• esophageal bleeding;
• Perforation of the esophageal wall with the development of peritonitis
/ purulent mediastinitis;
• Barrett's esophagus (see below).
Barrett's esophagus is one of the serious complications of GERD,

a condition of the esophagus in which the epithelial lining of the
esophageal mucosa shows an uncharacteristically normal
cylindrical intestinal-type epithelium instead of a squamous
multilayered epithelium.
87
Lower esophageal cell metaplasia is considered a condition caused by

chronic acid damage.
Barrett's esophagus is found in approximately 10% of patients
presenting for heartburn and in 1% of the general population. It is an
obligatory precancerous condition because it is associated with an increased
risk of cardioesophageal cancer and adenocarcinoma of the lower third of the
esophagus (esophageal cancer).
Long segments of cylindrical epithelium extending up the

esophagus, over the region of the esophageal-gastric junction,
which have a
characteristic red color and "velvet" appearance.
Limited replacement of layers of squamous epithelium by

specialized intestinal epithelium (intestinal metaplasia). Both
the surface of the mucosa and glands
of the intestinal type are lined by cylindrical epithelium
consisting of mucous and bocaloid cells.
► CANCER DIGESTIVE◄
Esophageal cancer accounts for 2-5% of all malignant neoplasms. It

occurs more often at the level of the middle and lower third of the
esophagus, which corresponds to the projection of the tracheal bifurcation.
Much less often - in the initial part of the esophagus and at the entrance to
the stomach.
ETHIOLOGY
Major risk factors that may contribute to esophageal cancer include:
• Constant intake of hot, coarse and poorly chewed food;
• alcohol consumption;
• smoking;
• Barrett's esophagus;
• esophagitis;
• diverticulitis;
• thermal and chemical burns of the esophagus, accompanied by
scarring, etc.
CLASSIFICATION, PATHOLOGIC ANATOMY

By macroscopic features:
88
• Annular dense cancer - a tumor mass that circularly covers the

esophageal wall, resulting in a narrowing of the lumen;
• Papillary cancer - grows exophytically in the form of individual
nodules, i.e. in the lumen of the esophagus, and quite early
undergoes decay;
• An ulcerated cancer is a cancerous ulcer that is oval-shaped and
extends along the esophagus.
By type of growth:
• exophytic cancer - nodular, mushroom, papillomatous - grows
from the mucosa into the esophageal lumen, prone to decay, has
a more benign course and later metastasis;
• Endophytic cancer - characterized by circular growth, faster
metastasis and early sprouting into surrounding tissues.
By histologic structure:
• carcinoma in situ;
• Squamous cell cancer - most common - can be with or without
keratinization depending on the degree of differentiation;
• adenocarcinoma;
• glandular squamous cell cancer;
• glandular cystic cancer;
• mucoepidermal cancer;
• undifferentiated cancer.
Metastasis of esophageal cancer is predominantly lymphogenic.
Complications:
• Sprouting into neighboring organs (trachea, stomach, mediastinum,
pleura);
• esophageal-tracheal fistula;
• aspiration pneumonia;
• abscess and gangrene of the lung;
• purulent mediastinitis;
• cachexia due to severe dysphagia.
89
STOMACH DISEASES
Among stomach diseases, gastritis, peptic ulcer disease and stomach

cancer are the most important.
► GASTRITIS◄
Gastritis is an inflammation of the mucous membrane of the stomach.
ACUTE GASTRITIS ETIOLOGY

There are two main groups of factors in the etiology of acute gastritis:
• exogenous factors - irritation of the mucosa difficult to digest food,
alcohol, d r u g s , the action of microorganisms;
• endogenous factors - the action of the damaging factor is mediated and
carried out by vascular, nervous, humoral and immune mechanisms -
infectious hematogenous gastritis, eliminative gastritis in uremia,
allergic gastritis, etc.
CLASSIFICATION AND PATHOLOGIC ANATOMY

By prevalence:
• diffuse gastritis;
• focal gastritis:
- fundamental;
- antral;
- pyloroantral;
- pyloroduodenal;
By morphologic changes in the gastric mucosa:
• catarrhal (simple);
• fibrinous;
• purulent (phlegmonous);
• necrotic (corrosive).
Catarrhal gastritis
mucous membrane mucous membrane of the
stomach thickened, edematous,
hyperemic, surface its abundantly covered
with mucous masses, and there are multiple small
90
hemorrhages, erosions.
Dystrophy, necrobiosis and sloughing of the superficial

epithelium, the cells of which are characterized by increased
mucus production. Sloughing of cells leads to erosion (erosive
gastritis). Glands change slightly, but their secretory activity is
suppressed. The mucosa is permeated with serous, serous-
mucous or serous-leukocytic exudate. The native layer is full
bloody and edematous, infiltrated with neutrophils,
there are diapedesis hemorrhages.
Fibrinous gastritis
A gray or yellow-brown fibrinous film is formed on the surface of the
thickened mucosa. The depth of necrosis of the mucous membrane can be
different, in this regard, there are croupy (superficial necrosis) and
diphtheritic (deep necrosis) variants of fibrinous gastritis.
Purulent (phlegmonous) gastritis

The gastric wall is sharply thickened due to mucosa and
submucosa layer. The mucosa folds are rough, with
hemorrhages, fibrinous-purulent deposits. From the surface of
the incision flows
yellow-green purulent fluid.
A leukocytic infiltrate containing a large number of

microorganisms diffusely covers the mucosa, submucosa and
muscle layers of the stomach and the
covering his peritoneum. Perigastritis and peritonitis.
Necrotic gastritis
It usually occurs when chemical substances (alkali, acid, etc.) enter the
stomach, cauterizing and destroying the mucosa (corrosive gastritis).
Necrosis (coagulation or colliquation) can cover superficial or deep sections
of the mucosa. Necrotic changes usually end with the formation of erosions
and acute ulcers.
The outcome of acute gastritis depends on the depth of the lesion of the
gastric mucosa . Catarrhal gastritis may end in complete
91
by repairing the mucous membrane. With frequent recurrences, it can lead to

the development of chronic gastritis.
After significant destructive changes characteristic of phlegmonous and
necrotic gastritis, mucosal atrophy and sclerotic deformation of the gastric
wall (gastric cirrhosis) develop. Necrotic changes can lead to the
development of phlegmon and perforation of the gastric wall.
CHRONIC GASTRITIS
Chronic gastritis - inflammation of the gastric mucosa, in the

genesis of which a significant role is played by violations of the
processes of its regeneration and structural reorganization.
Chronic gastritis accounts for 35% of all gastroenterologic diseases and

60-85% of all gastric diseases.
CCASSIFICATION.
Figure 27: Classification of chronic gastritis.
Below is a brief characterization of each type of chronic gastritis

depending on the features of etiopathogenesis:
Gastritis A is autoimmune gastritis.

• An autoimmune disease associated with the appearance of
autoantibodies to parietal cell lipoprotein and intrinsic factor that
block its binding to vitamin B12;
92
• often combined с other autoimmune (thyroiditis,

Addison's disease);
• manifests itself primarily in children and the elderly;
• localized in the fundus;
• characteristic sharp decrease secretion hydrochloric
(achlorhydria), G-cell hyperplasia and gastrinemia;
• accompanied development pernicious (B12-deficiency)
anemia.
Gastritis B is not immune gastritis

• the most common form of chronic gastritis;
• etiology is attributed to Nelysobacter ru1ori, which is
found in almost 100% of patients;
• Various endogenous and exogenous factors also play a role in the
development (intoxication, eating disorders, alcohol abuse);
• localized in the antral section, can spread to the entire stomach
(pangastritis).
Gastritis C is reflux gastritis.

• is due to the duodenal contents being thrown into the stomach;
• often occurs in people who have had a gastric resection;
• localized in the antral region;
• HCl secretion is not disturbed and the amount of gastrin is not changed;
• on the topography of the process distinguish antral, fundal
gastritis and pangastritis.
Modified Sydney classification of gastritis

Etiological factors
Type of gastritis Synonyms
1. Nonatrophic Superficial, diffuse, antral, Helicobacter pylori,
interstitial, other factors
hypersecretory, type B
2. Atrophic: Diffuse gastritis of the

- autoimmune gastric body associated Autoimmune
with
- multifocal pernicious anemia, H. pylori, dietary
type A. patterns, exogenous
factors
3. special forms: Reactive reflux- Chemical
93
- chemical gastritis type C irritants, bile

- radiation Gastritis, Radiation lesions
- lymphocytic associated с Idiopathic
- non-infectious celiac disease Immune
granulomatous Isolated mechanisms
- eosinophilic granulomatosis Disease
Crohn's
,
- other infections Food allergy sarcoidosis,
granulomatosis
Wegener's
Allergic
Bacteria (except H.
pylori), viruses,
fungi, parasites
Superficial (non-atrophic) gastritis

Hyperemia, edema of the gastric mucosa, erosions may be
present.
Dystrophy of the superficial epithelium. In some areas it is

flattened, close to cubic and characterized by reduced secretion,
in others - high prismatic с increased
secretion. Lymphoplasmocytic infiltrate
is located in the superficial parts of the gastric mucosa on the
at the level of the rollers.
Superficial gastritis is more often inactive. If it becomes active, then

stromal edema develops, pronounced vascular hypertension, and
polymorphonuclear leukocytes appear in the infiltrate and leukopedesis
(infiltration of leukocytes into epithelial cells) develops. The severity of
neutrophilic infiltration can be different - from moderate leukocytic
infiltration of the intrinsic lamina to the formation of "intrinsic abscesses"
and erosions on the surface of the mucosa. The prognosis is usually
favorable. In some cases, it can turn into atrophic gastritis.
Atrophic gastritis
Atrophy of the mucosaof the mucous membrane, its
glands, which determines the development
of sclerosis.
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The mucous membrane is thin, the number of glands is reduced.

Diffuse lymphoid-plasmocytic infiltrate, pronounced sclerosis
in the intrinsic lamina. Structural rearrangement with
appearance of intestinal and pyloric metaplasia foci is
characteristic. Often
focus of dysplasia occurs. On the background of severe
dysplasia of the epithelium, gastric cancer may develop.
In chronic gastritis, along with the epithelium characteristic of each

section of the stomach often appears epithelium that is not peculiar to it, ie
there is a structural reorganization of the epithelium, or metaplasia. Two
variants of metaplasia are possible:
• pyloric metaplasia - glands resembling mucous or pyloric
glands appear in the area of the fundal glands (i.e., in the body
of the stomach). These glands are called pseudo-pyloric glands
of Sterck;
• intestinal metaplasia (enterolization) - the gastric m u c o s a in
appearance resembles the intestinal mucosa with characteristic
villi instead of rolls:
- complete (small intestinal) metaplasia - presence of caemic
enterocytes, bocaloid cells and Paneth cells in crypts;
- incomplete (colonic) metaplasia - epithelial cells resemble
colonocytes, there are many bocaloid cells, and Paneth
cells are absent.
Metaplastic epithelium under certain conditions may underlie
dysplasia and malignization.
Earlier, a form of hypertrophic gastritis (Menetrier's disease) was
distinguished, but recently instead of it the concept of hyperplastic
gastropathy has been introduced. In the absence of inflammation in this case,
there is thickening of the folds of the mucosa, hyperplasia of glands due to
various factors, in particular endocrine.
► PEPTIC ULCER DISEASE
Peptic ulcer disease is a chronic disease characterized by a long-

lasting, intermittently healing ulcerative defect in the wall of the
stomach or 12-per colonic intestine.
95
Peptic ulcer disease affects 2-3% of the adult population, with urban
residents about 2 times more often than rural residents, and men - 4 times
more often than women.
ETHIOPATOGENESIS
Gastric and duodenal ulcer disease is a polyetiologic disease. The
disease is based on the discrepancy between the protective mechanisms of
the gastric / duodenal mucosa and damaging factors (factors of
ulcerogenesis), among which we can distinguish external (exogenous) and
internal (endogenous).
Factors of Ulcerogenesis
Exogenous Endogenous
• genetic predisposition; • violation of the
• Helicobacter gastritis and regime and nature of
metaplasia of the epithelium nutrition;
in the duodenum; • bad habits;
• Hyperproduction of • neuropsychiatric
hydrochloric acid and overexertion;
pepsin; • occupational factors;
• Gastroduodenal • drug exposures.
motility disorder;
• age and gender.
MORPHOGENESIS AND PATHOLOGIC ANATOMY

In the morphogenesis of peptic ulcer disease it is customary to
distinguish the following stages:
1. Erosion is a superficial defect resulting from necrosis of the mucous
membrane;
2. An acute ulcer is a deep defect involving the mucosa and underlying
membranes of the gastric wall. It has an irregular round-oval shape
and soft edges. The bottom of erosions and ulcers is dirty brown due
to hydrochloric acid hematine.
3. Chronic ulcer - is usually located on its small curvature along the
course of the so-called food path, more often in the area of the
gatekeeper and the body of the stomach. The relief of the mucous
membrane is usually altered, to it rays converge folds, or folding can
be smoothed. The edges of the ulcer are valley-shaped raised,
compacted. With significant expression of this sign say the callous,
that is, omozoleloy ulcer Proximal edge is usually undermined and
overhanging the bottom distal - more
96
flat. If the ulcer is located in the area of the gatekeeper or bulb of the
12-intestine, there is usually a narrowing (stenosis) of the digestive
tube.
The microscopic picture depends on the stage of the peptic ulcer.

In the remission stage, scar tissue displacing the muscular layer
with single sclerosed and obliterated vessels can be seen in the
bottom of the ulcer. Epithelialization of the ulcer is often noted.
In the acute stage, 4 layers are clearly distinguishable in the
bottom of the ulcer:
• fibrinous purulent exudate,
• fibrinoid necrosis,
• granulation tissue,
• fibrous tissue in which sclerosed tissue is visible
vessels. Fibrinoid necrosis is noted in the walls of some
vessels.
Complications of peptic ulcer disease
Figure 28: Complications of gastric and duodenal ulcer disease.

97
► CANCER GASTRIC◄
Gastric cancer is a malignant tumor originating from the

epithelium of the gastric mucosa.
Gastric cancer is one of the most common cancers and ranks 2-4 in the
structure of cancer morbidity (depending on the region).
ETHIOLOGY
The following risk factors are important in the development of gastric
cancer:
• Age - more common in the elderly (95% of stomach cancers
occur in people over the age of 55);
• the presence of Helicobacter pylori infection;
• chronic inflammation;
• smoking;
• family history;
• An unbalanced diet or obesity;
• lack of physical activity;
• chemical agents;
• ionizing radiation.
Precancerous conditions include polyposis and dysplasia. The latter is
manifested by atypism of individual epithelial cells or metaplasia of highly
differentiated glands of the stomach (usually producing enzymes) into
mucus-secreting glands, i.e. metaplasia into intestinal-type epithelium. Peptic
ulcer disease does not qualify as an obligate precancerous condition.
Ulceration develops into cancer in only 3-5% of cases.
CLASSIFICATION AND PATHOLOGIC ANATOMY
• gastric adenocarcinoma is the most frequent histologic type of

gastric cancer. Cellular atypism is insignificantly expressed, but the
basal membrane is sprouted by cancer cells (highly differentiated
adenocarcinoma).
• solid cancer - the glandular cells are completely filled with cancer
cells (no lumen).
• skirr - a dense tumor in which histologically fibrous tissue
predominates; individual cancer cells and their complexes are
scattered in it, i.e. stroma predominates over parenchyma.
98
• medullary (medullary) cancer - a tumor of soft consistency,

histologically the parenchyma predominates, there is little stroma.
• ring-shaped and mucinous gastric cancer - the cancer cells have the
appearance of "rings", i.e. the cytoplasm is filled with mucus and the
nucleus is pushed back to the membrane.
Figure 29: Classification of gastric cancer.

99
For the purpose of determining the tactics of patient management, the following are
also distinguished
Lauren's classification of gastric cancer:
• "Intestinal" type of gastric cancer - adenocarcinomas of varying
degrees of differentiation;
• "Diffuse" type of gastric cancer - undifferentiated and pistilliform cell
cancer, poorly differentiated adenocarcinomas.
Metastasizing:
• Regional metastases of gastric cancer - to the lymph nodes of the small
and large curvature and liver + implantation metastasis:
carcinomatosis of the peritoneum, diaphragm, omentum, etc.;
• distant metastases:
- "Virchow's" to the lymph node above the left clavicle;
- "kruckenberg's" to both ovaries;
- "Schnitzler's metastasis" to the pararectal tissue;
- "Sister Mary Joseph's metastasis" to the navel.
Complications (including fatal ones) in gastric cancer may occur due to
necrosis and inflammatory processes in the tumor itself. In these cases,
perforation of the wall, bleeding, peritumorosis gastritis, phlegmon of the
stomach are possible. There are also complications due to the sprouting of
the tumor and its metastases adjacent tissues. When the tumor sprouts
through the head of the pancreas or hepatic-duodenal ligament develop
jaundice, ascites, portal hypertension. The most common in gastric cancer
develops cachexia due to starvation of patients and severe intoxication, as
well as severe iron deficiency anemia.
INTESTINAL DISEASES
► APPENDICIT◄.
Appendicitis is an inflammation of the worm-shaped outgrowth of

the cecum.
ETHIOPATOGENESIS
Most often most often caused acute appendicitis are
obstruction lumen appendix fecal matter or enlarged
100
in the submucosa as a result of lymphoid hyperplasia, as well as when the

appendix is kinked. In this case, there is increased multiplication of
microorganisms such as Escherichia coli, Streptococcus faecalis and
anaerobic bacteria in the distal segment. These bacteria then penetrate the
mucosa and other membranes of the appendix, causing acute inflammation.
CLASSIFICATION
There are two clinical and anatomical forms of appendicitis: acute and
chronic.
Acute appendicitis is the most common cause of surgical emergencies. It
occurs in all age groups, but most commonly in adolescents.
Figure 30. Classification of acute appendicitis and its complications.
Simple appendicitis
worm-like outgrowth thickened, serous the
serous membrane is dull. Under the serous membrane there are
many filled
with blood in the small vessels.
101
Blood stasis in capillaries and venules, edema, hemorrhages,

accumulation of siderophages, marginal standing of leukocytes
and
Leukodiapedesis (primary affect formation).
Superficial appendicitis
The vermiform process becomes swollen, the serous membrane
is full blooded and dull
Defects of the mucous membrane covered with fibrin films.

There is leukocytic infiltration in the submucosal layer.
Primary Aschoff's affect (focus of purulent exudative
inflammation) - is located in the depth of mucosal furrows and
has the shape of a wedge,
spreading into the underlying tissue.
Phlegmonous and phlegmonous-ulcerous appendicitis

worm-like outgrowth enlarged, serous
membrane is dull, bloody, covered with
fibrinous plaque;
walls thickened, from the from the lumen and
there's a discharge purulent contents.
Diffuse infiltration of the entire thickness of the outgrowth with

leukocytes. On the side of the mucous membrane there are
ulceration, suppuration and often its necrotization and
partial rejection (phlegmonous ulcerative
appendicitis).
Gangrenous appendicitis is caused by thrombosis or thromboembolism of

the mesenteric artery of the appendix (primary gangrenous appendicitis) or
by its thrombosis due to the development of periappendicitis and purulent
mesenteriolitis (secondary gangrenous appendicitis).
The vermiform process is considerably thickened, earthy-
gray color, с fibrinous purulent with fibrinous
purulent deposits. The wall is flabby, easily perforated
Edema, hemorrhages, leukocytic infiltration

and necrosis of the entire wall of the worm.
Apostematous appendicitis.
102
Consistent with phlegmonous appendicitis.
Small abscesses form in the wall, represented by necrotized

tissue и neutrophils
white blood cells.
Chronic appendicitis is characterized by the presence of sclerotic and

atrophic processes, against which signs of inflammatory-destructive changes
can be detected. Adhesions with surrounding tissues arise. With scar
obliteration of the proximal section in the lumen of the worm may
accumulate serous fluid and form a cyst - hydrocele of the process. If the
contents of the cyst are mucus, this complication is referred to as a mucocele.
If such a cyst ruptures and the contents enter the abdominal cavity, cells may
implant on the peritoneum and develop tumor-like masses - peritoneal
pseudomyxoma.
Appendicopathy is a pathologic condition with a clinical picture

consistent with appendicitis, due to impaired motility of the vermiform
process.
Pseudoappendicitis (false appendicitis) is a symptom complex
resembling appendicitis, but caused by other diseases (e.g., in peptic ulcer
disease, renal stone disease, cholelithiasis, adnexitis, etc.).
► NONSPECIFIC ULCERATIVE COLITIS◄
Nonspecific ulcerative colitis (NUC) is a chronic inflammatory

disease of the colonic mucosa resulting from the interaction
between genetic and environmental factors, characterized by
exacerbations.
In temperate countries, nonspecific ulcerative colitis (NUC) is the

leading cause of diarrhea with blood, mucus and pus. NUC is a nonspecific
inflammatory disease of the colon that develops usually in the rectum and
then spreads proximally. Only the colon is affected by NPC.
103
The incidence rate averages 12-140 cases per 100,000 people.

ETHIOPATOGENESIS
NNC is a polyetiologic disease, but its etiology is not precisely
established. The following etiologic factors are currently considered:
• genetic predisposition (having relatives with Crohn's disease or NNC
increases the risk of developing ulcerative colitis);
• infectious agents (bacteria, viruses), but their role is not completely
clear;
• environmental factors - use of oral contraceptives, smoking, diets, etc.
Autoimmune processes are thought to underlie the pathogenesis of
NNC, and mucosal damage occurs as a result of inadequate activation of T-
lymphocytes and mediated damage by cytokines, proteases, and oxygen
radicals synthesized by macrophages and neutrophils.
Acute form
The colon wall is edematous, hyperemic, with multiple erosions
and superficial ulcers of irregular shape, which merge to form
extensive areas of ulceration. The preserved islets of mucous
membrane in these areas resemble the
polyps (fringed pseudopolyps).
At the bottom of ulcers vessels with fibrinoid necrosis and

arrosion of the walls. Often - perforation of the intestinal wall
in the area of the ulcer and intestinal bleeding. In some ulcers -
overgrowth of granulation tissue, forming polyp-like
outgrowths (granulomatous pseudopolyps). The intestinal wall,
especially the mucosa, is infiltrated with lymphocytes, plasma
cells, and plasma cells.
cells, eosinophils. During exacerbation, neutrophils
predominate in the infiltrate (crypt abscesses).
Chronic form
Abrupt thickening and thickening of the intestinal wall, as well
as diffuse or segmental narrowing of its lumen.
104
Reparative-sclerotic processes prevail over inflammatory-

necrotic ones. Granulation
and scarring of ulcers occur, but epithelization is incomplete.
Pseudopolyps are formed from granulation tissue
(granulomatous pseudopolyps) and due to reparative
regeneration of epithelium (adenomatous pseudopolyps).
Inflammation has predominantly productive character and is
expressed in infiltration
of the intestinal wall by lymphocytes, histiocytes and plasma
cells.
Complications:
1. Malignancy - the overall incidence of colorectal cancer in NSCLC
patients is 2%.
2. Local complications:
• bleeding;
• electrolyte disorders (prolonged diarrhea);
• toxic dilatation and perforation with the development of fecal
peritonitis;
3. Common complications:
• Skin - nodular erythema (subcutaneous inflammation) and gangrenous
pyoderma (sterile skin abscesses);
• Liver - pericholangitis (inflammation around the bile ducts),
sclerosing cholangitis (fibrotic narrowing and obliteration of the bile
ducts), cholangiocarcinoma and active chronic hepatitis;
• eyes - iritis, uveitis and episcleritis;
• joints - increased risk of ankylosing spondylitis.
► CROHN'S DISEASE
Crohn's disease is a chronic recurrent disease of the

gastrointestinal tract characterized by nonspecific
granulomatosis and necrosis.
Chronic inflammation and ulceration in this disease is most commonly

seen in the terminal segment of the small intestine, but all parts of the
digestive tract may be affected: from the
105
the oral cavity to the rectum. The skin may also be affected, most often in the
perianal area.
The disease usually occurs in young people: in more than 50% of cases
the age of patients is 20-30 years, in 90% - from 10 to 40 years. Men are
affected somewhat more often than women. The frequency is 2-3 per 1000
people.
ETHIOPATHOGENESIS
As with nonspecific ulcerative colitis, the etiology is not fully
understood. There are 3 main groups of factors:
• genetic factors;
• infectious factors;
• immunologic factors.
The mucosa is lumpy, resembling a "cobblestone sidewalk",
which is due to the alternation of long, narrow and deep ulcers,
which are located in parallel rows along the intestine, with areas
of normal mucosa. Deep transverse slit-shaped ulcers. The
serous membrane is covered with adhesions and multiple
with whitish nodules. The lumen of the intestine is narrowed.
The mesentery is thickened, sclerosed.
Nonspecific granulomatous An
inflammation involving all layers of the intestinal wall.
Granulomas consist of epithelioid and giant Pirogov-Langhans
cells. Edema and diffuse infiltration with lymphocytes,
histiocytes, plasma cells of submucosal layer, hyperplasia of
lymphoid elements. Characteristic
"slit-shaped" ulcers. Inflammatory infiltrate in the intestinal
wall is located in large foci.
Complications:
• malabsorption syndrome;
• Intestinal and intestinal-dermal fistulas;
• rectal fissures and fistulas;
• Perforation of the intestinal wall, bleeding, and toxic
dilatation are less common than in NSCLC;
• Malignization is less common than in NPC;
106
• systemic amyloidosis - rare.

Given the similarity of clinical and morphologic manifestations
and complications of nonspecific ulcerative colitis and Crohn's disease,
the criteria for differential diagnosis of these two diseases are presented
below.
Differential diagnostic features of NNC and Crohn's disease

Signs NNC Crohn's disease
Symptoms Diarrhea with blood, Abdominal pain, more often in
mucus and sometimes the left lower quadrant, bloody
pus diarrhea is not characteristic
Localization of the Within the colon and It can localize
pathological always in the rectum in any part of the GI
process tract
Endoscopic picture Granularity, loss of Cobblestone" type, slit-shaped
vascular pattern, ulcers on the background of
presence little changed mucous
of erosions, areas of membrane, more often in the
ulceration, process involves the
pseudopolyps distal of the
ileum
Histological Crypts twisted, At the edge of the "slit-shaped"
ulcers, on the
painting distributed at the site of healed ulcers is
common
unevenly, mucosal structure
diffuse disturbed. There are
uniform microgranulomas,
inflammatory granuloma-like
process. of education, i.e.. different
Characteristically cluster size and shape
pericryptal macrophages, comprising
cluster sometimes и large
neutrophils, epithelioid cells.
the
ir
leukopaedesis с There are definite vasculitides
shaping various degrees
crypt abscesses. of expression,
someti
mes
sclerosis of the blood vessels.
Crypt
abscesses are rare.
и accompanied death
107
of the crypt epithelium.

108
► COLORECTAL CANCER COLON◄
About 98% of malignant bowel tumors are adenocarcinomas. The age

of patients is 60-80 years. Predisposing factors: intestinal polyposis, diet low
in fiber, high in carbohydrates and red meat.
The rectosigmoid colon is affected in 55% of cases.
Macroscopic shapes:
• Exophytic cancer - polyp-like and villous forms;
• Endophytic cancer - ulcerative and diffuse forms.
In the ampullary rectum, it is usually polyposis or villous or ulcerated
cancer with roller-shaped margins. In the rectosigmoid, it is more often
diffuse cancer in the form of a whitish dense ring narrowing the intestinal
lumen.
Microscopic forms:
• adenocarcinomas of various degrees of differentiation,
• undifferentiated cancer (solid
and papillary cell.)
Metastasizes to regional lymph nodes and hematogenously to the liver.
109
SECTION V
DISEASES OF THE LIVER, GALLBLADDER AND PANCREAS
LIVER DISEASE
Liver diseases include a number of pathological conditions
characterized by different etiology, pathogenesis, and diverse clinical and
morphological manifestations, each of which may be dominated by
dystrophy, inflammation, or sclerosis.
Of the variety of pathological processes occurring in liver diseases, the
most common are alterative processes (dystrophy, necrosis, apoptosis of
hepatocytes), inflammation (including immune inflammation), and
adaptation and compensatory processes (see Fig. 31).
Fig. 31. Schematic representation of the most frequent pathologic processes in

liver diseases.
110
Of greatest clinical and morphological significance are hepatoses,

hepatitis, liver cirrhosis, and primary tumors of the hepatobiliary system.
► HEPATOSES◄
Hepatoses are a group of pathological conditions of the liver

characterized mainly by dystrophy and necrosis of hepatocytes.
ETHIOPATOGENESIS
Among the leading etiopathogenetic factors leading to the
development of hepatosis are:
• poisoning (phosphorus, arsenic, alcohol, drugs, mushrooms,
food);
• hepatitis;
• sepsis;
• hereditary metabolic disorders;
• Hypoxia in cardiopulmonary pathology.
Depending on the course, acute and chronic hepatoses are

distinguished, and depending on the etiology: hereditary and acquired.
ACUTE HEPATOSIS
Acute hepatosis (toxic liver dystrophy, massive liver necrosis) is a

clinical and morphological syndrome characterized by extensive
(massive) liver necrosis accompanied by the development of liver
failure.
ETHIOLOGY
Acute hepatosis is based on acute toxic damage to the liver
parenchyma by hepatotropic toxins of exogenous or endogenous origin:
• foodborne toxic infections;
• mushroom poisoning;
• alcohol poisoning;
• heavy metal salts, arsenic;
• toxicosis of pregnancy;
• thyrotoxicosis, etc.
111
In the morphogenesis of acute hepatosis, 2 stages are distinguished:
• "yellow dystrophy" stage of the liver - 2 weeks;
The liver is enlarged, dense or flabby, bright yellow in color.
Then it decreases, becomes flabby, and the capsule is wrinkled,
on the cut the liver tissue is gray, clay or ochre-yellow (due to
impregnation of necrotic parenchyma with bile and
fatty degeneration of hepatocytes).
Fatty dystrophy of hepatocytes, mainly in the center of the

lobules. Fatty dystrophy is rapidly followed by necrosis of
hepatocytes and formation of fatty and
of protein detritus.
• the "red dystrophy" stage of the liver is week 3.

The liver is shrunken, flabby consistency. The color on the
section is red. The capsule is shriveled. In subacute course there
are many fine-grained areas on the liver surface, formed by
granulation overgrowth.
tissue at the site of necrosis.
Different size foci of necrosis localized mainly in centrilobular

sections with exposure of blood vessels and stroma of the
organ. Among necrotic masses there are accumulations of
macrophages, stellate reticuloendotheliocytes, segmented
leukocytes. There are often hemorrhages, in portal tracts
inflammatory infiltration is poorly expressed. In preserved
hepatocytes (on the periphery of the lobule) there are -
fatty dystrophy.
The outcome of acute toxic dystrophy: death from liver failure or transition
to postnecrotic cirrhosis of the liver. Death occurs at phenomena of
parenchymatous dystrophy of organs, in particular heart.
CHRONIC HEPATOSIS
Chronic hepatosis is is a pathological

condition characterized mainly by fatty dystrophy
112
hepatocytes. In clinical practice, depending on the etiology, such nosological

units as "nonalcoholic fatty liver disease", "nonalcoholic steatohepatosis"
and "alcoholic liver disease" (alcoholic steatosis of the liver) are used.
ETHIOLOGY
• alcohol is the primary cause;
• metabolic disorders - diabetes mellitus (more often in the elderly),
general obesity, protein and vitamin deficiencies (with inadequate
nutrition or due to chronic diseases of the digestive system);
• Chronic intoxication with carbon tetrachloride,
organophosphorus compounds, bacterial toxins;
• toxic effects of drugs - phenothiazine derivatives (aminazine),
hormonal steroid drugs (testosterone analogs, estrogens, gestagens),
anticoagulants, antibiotics;
• hereditary diseases - enzymopathies: Gilbert syndrome, Kriegler-
Nayar syndrome, etc.
The morphological manifestation of chronic hepatosis is
parenchymatous fatty dystrophy of the liver ("goose liver"), although some
morphological manifestations (depending on the etiology) are characterized
by cholestatic or pigmented hepatosis.
In its development, fatty hepatosis goes through 3 stages:
• simple obesity - parenchymatous fatty dystrophy of the liver,
destruction of hepatocytes is not expressed, mesenchymal cell reaction
(inflammation) is absent;
• Liver obesity combined with hepatocyte necrobiosis and
mesenchymal-cell reaction;
• liver obesity with beginning reorganization of the lobular structure of
the liver (precirrhotic stage).
The liver is enlarged, yellow or red-brown, surface smooth, edge

rounded ("goose liver").
Hepatocytes in a state of parenchymatous fatty dystrophy

(dusty, small- or large-drop obesity). There may be
disseminated
113
obesity (single hepatocytes), zonal obesity (groups of

hepatocytes) or diffuse obesity (entire liver parenchyma). Fatty
dystrophy develops predominantly centrilobularly
(intoxication, hypoxia) or periportally (protein-vitamin
deficiency). In the second stage (with necrobiosis) -
hepatocytes die, fat droplets merge and form extracellular fat
cysts with inflammation and overgrowth
connective tissue (precirrhotic stage).
Fatty liver dystrophy at the first two stages is a reversible process. As it
progresses, it is accompanied by hepatic insufficiency. In the transition to the
precirrhotic stage - irreversible with the outcome in liver cirrhosis.
► HEPATITES◄
Hepatitis - acute or chronic diffuse inflammatory diseases of the

liver of various etiologies, manifested by hepatocyte alteration
and inflammatory infiltration phenomena.
ETHIOPATOGENESIS
Depending on the etiology, primary and secondary hepatitis are
distinguished:
• primary hepatitis:
- viral;
-toxic (alcohol, medications);
- autoimmune;
• secondary hepatitis (nonspecific reactive hepatitis):
-infection (yellow fever, cytomegalovirus, typhoid fever,
dysentery, malaria, tuberculosis, sepsis);
-intoxication (thyrotoxicosis, hepatotoxic poisons);
-diseases of the gastrointestinal tract;
-systemic connective tissue diseases, etc.
114
Figure 32. Classification of hepatitis.
In clinical practice, viral, alcoholic and autoimmune hepatitis are most

important.
VIRAL HEPATITIS ETIOLOGY

• Hepatitis A virus - causes epidemic viral hepatitis (Botkin's disease).
Transmission is fecal-oral. The incubation period is 15-45 days. There
is direct cytotoxic damage to hepatocytes. The prognosis is favorable,
not prone to chronicization. Death only in the transition to toxic
dystrophy;
• Hepatitis B virus - transmission is parenteral. The disease is called
"serum hepatitis". The incubation period is 25-180 days. It is
accompanied by virosemia, lymphadenitis, and is often associated
with HIV/AIDS infection;
• Hepatitis C virus - the route of transmission is parenteral; often occurs
as post-transfusion hepatitis with predominantly jaundice-free forms
and is prone to chronicization.
115
Incubation period 15-150 days. Rapidly progresses with the

development of chronic forms of hepatitis;
• hepatitis D virus is a defective RNA-containing virus. Infection with
hepatitis D can occur either together with hepatitis B infection
(coinfection) or superimposed on chronic hepatitis B infection
(superinfection). In both cases, patients' symptoms are more severe
than with hepatitis B infection alone. Patients infected with both
hepatitis B and hepatitis D are much more likely to develop terminal
liver failure as a result of acute infection, rapid development of
cirrhosis, and, in the case of chronic infections, an increased risk of
hepatocellular carcinoma;
• Hepatitis E virus - transmission route is fecal-oral, propensity for
epidemic spread. The course
is predominantly benign, not prone to chronicity;
• other viruses - herpes simplex virus, yellow fever virus,
cytomegalovirus, measles virus, etc. - extremely rare.
PATHOGENESIS.
The pathogenesis of liver damage in viral hepatitis is complex and
includes many pathogenetic factors. At the same time, two possible
mechanisms underlie the damage of hepatic cells by hepatotropic viruses:
• The direct cytopathogenic effect of viruses;
• Induction of an immune response against viral antigens or antigen of
virus-infected hepatocytes.
The following are distinguished
following clinical and morphological forms
of viral hepatitis (the first 4 are acute):
• cyclic jaundice;
• the jaundiced form;
• Necrotic (lightning, fulminant) form (viral hepatitis with massive liver
necrosis);
• cholestatic form;
• chronic form:
-Chronic active hepatitis (CAH);
-Chronic persistent hepatitis (CPH).
Acute cyclic (jaundiced) form

116
The liver is enlarged, dense; the color on the section is red; the
capsule is tense ("big red liver").
Hydropic (balloon) dystrophy of hepatocytes; focal (spotty) and

confluent necrosis of hepatocytes in different parts of lobules.
Kaunsilmen's bodies - in the form of rounded eosinophilic
homogeneous formations with a pyknotic nucleus or without a
nucleus (hepatocytes killed by apoptosis). Periportal step
necroses (death of hepatocytes of the border lamina). Diffuse
infiltration (mainly periportal) by lymphocytes and
macrophages with an admixture of plasma cells.
cells, eosinophils and neutrophils.
The jaundiced form

Balloon dystrophy, foci of hepatocyte necrosis, and
Caunsilman's corpuscles are rare. Inflammatory lymphocytic-
macrophagal infiltrate
in the periportal area,
but no step necrosis.
No cholestasis.
Necrotic form
The liver is reduced in size, the capsule is wrinkled. The color
on the section is gray-brown or yellow. Consistency
flabby.
Bridging or massive necrosis of hepatocytes. Among necrotic

masses there are Caunsilman's corpuscles, accumulations of
Kupffer cells, lymphocytes, macrophages, neutrophils. Stasis of
bile in capillaries is sharply expressed. Hepatocytes are
determined only in the preserved parenchyma on the periphery
of lobules (in the state of
hydropic or balloon dystrophy).
Cholestatic form
"Big red liver" with foci of yellow-green color and emphasized
lobular pattern.
117
Biliary capillaries and bile ducts of portal tracts are full of bile,
bile pigment accumulates in hepatocytes and Kupffer cells.
Hepatocytes of centralsections are in thestate
of hydropic or balloon dystrophy, there are Caunsilman's
corpuscles. Portal tracts are dilated, infiltrated mainly by
lymphocytes, and
by macrophages.
Chronic persistent hepatitis.

Has a recurrent course, in which there is no progressive liver damage with
the outcome in cirrhosis and the development of liver failure.
Moderate periportal infiltration with lymphocytes, histiocytes
and plasma cells. The border lamina and structure of hepatic
lobules are preserved. Dystrophic changes of hepatocytes are
expressed minimally or moderately (hydropic dystrophy),
necrosis of hepatocytes is rare. "Matte
vitreous hepatocytes, Cunsilman's corpuscles.
Chronic active hepatitis

Characterized by progressive destruction of hepatocytes over the next few
years, and the development of cirrhosis.
Portal, periportal and intravalvular infiltration of sclerosed
stroma. Dystrophy (hydropic, balloon) and necrosis of
hepatocytes: stepwise, bridge or submassive
(multilobular). Sclerosis and remodeling of liver tissue.
MORPHOLOGIC CRITERIA FOR DIFFERENTIAL DIAGNOSIS OF VIRAL

AND ALCOHOLIC HEPATITIS
Criterion Viral hepatitis Alcoholic hepatitis
Dystrophy Protein
Fat
hepatocytes (balloon)
Lymphocytic
Infiltration Neutrophilic
macrophage
Counsilman's
Mallory's corpuscles
Taurus (apoptotic.
Specific findings (intracytoplasmic inclusions
hepatocyte death cells)
of alcoholic hyaline)
118
• acute / chronic liver failure;
• renal and hepatic failure;
• cirrhosis of the liver (especially in chronic active hepatitis);
• Liver cancer (especially in chronic viral hepatitis C)
► CIRRHOSIS LIVER◄
Cirrhosis of the liver is a chronic liver disease accompanied by

irreversible replacement
of liver parenchymatous tissue with fibrous connective tissue.
The key characteristics of cirrhosis of the liver are:

• Hepatocyte dystrophy and necrosis;
• fibrosis;
• compensatory hyperplasia of hepatocytes with the formation of
regenerate nodules (false lobules);
• liver deformity.
CLASSIFICATION
• Etiology:
- post-infectious cirrhosis - viruses, parasites, syphilis ("lobular
liver"), bacterial infections of the biliary tract;
- toxic and toxicoallergic cirrhosis - alcohol, drugs, hepatotoxic
poisons;
- metabolic-alimentary cirrhosis - with the lack of proteins, vitamins,
lipotropic factors; Wilson-Konovalov disease (copper metabolism
disorder);
- Primary biliary cirrhosis - in destructive cholangitis or
cholangiolitis;
- secondary biliary cirrhosis - in case of biliary obstruction or
infectious (bacterial) cholangitis;
- Circulatory - as an outcome of chronic venous hyperemia
("muscular cirrhosis");
- cryptogenic-- of unknown nature;
• On the macroscopic picture:
119
- micro-nodular (micronodular) cirrhosis - regenerative nodules are

round, bordered by rings of connective tissue, not exceeding 5 mm
in diameter;
- macronodular (macronodular) cirrhosis (usually postnecrotic) -
nodes exceed 5 mm in diameter, in the same liver have different
size and irregular shape;
- mixed;
• By microscopic pattern:
- monolobular cirrhoses - with the formation of "false lobules"
without a central vein;
- Multilobular cirrhoses - with the formation of "false lobules" that
have many central veins;
• By morphogenesis:
- portal (septal);
- post-necrotic;
- mixed;
• By the nature of the flow:
- active;
- inactive.
All forms of cirrhosis lead to the development of hepatocellular failure, which

manifests:
• jaundice (more often of the mixed type);
• hypoalbuminemia;
• clotting factor deficiency;
• hyperestrogenemia (manifesting erythema palms,
telangiectasias, loss hair atrophy testicles и
loss,
gynecomastia).
Often in cirrhosis, portal hypertension develops, which manifests:

• varicose veins of the esophagus, anterior abdominal wall
("jellyfish head") and hemorrhoidal veins;
• splenomegaly;
• ascites.
There are often changes associated with both hepatocellular failure and portal
hypertension:
• edema, hydrothorax, ascites (associated with portal hypertension,
decreased oncotic oncotic pressure due to
120
hypoalbuminemia, as well as with sodium and water retention due to

decreased aldosterone cleavage in the liver);
• Encephalopathy (decreased detoxification in the liver, and toxic
substances entering the general circulation due to the portal
hypertension shunt system);
• neurological disorders.
The most common forms of liver cirrhosis are alcoholic (small-

nodular), viral (large-nodular), and biliary cirrhosis.
Alcoholic small-nodular portal cirrhosis of the liver

The liver may be enlarged, or it may be reduced (in the final);
dense, the surface is small-nodular, knobby; the size of the
nodes is not more than 0.5 cm; the nodes are gray-yellow in
color.
Parenchyma is represented by false lobules of uniform size,

separated by narrow layers of connective tissue - septa. In septa
lymphohistiocytic infiltration with admixture of
polymorphonuclear leukocytes, biliary proliferation
ducts. In false lobules there is no bar structure, fatty dystrophy
of hepatocytes is characteristic.
Viral postnecrotic large nodular cirrhosis of the liver

The liver is reduced, dense. The surface is lumpy, large-nodular;
nodes of uniform size, more than 1 cm,
separated by irregular layers of connective tissue.
The parenchyma is represented by false lobules separated by

massive fields of connective tissue, in which several triads in
one field of view are noted ("triad convergence phenomenon"
is a pathognomonic sign of postnecrotic cirrhosis). In
hepatocytes protein dystrophy (hydropic, balloon); for cirrhosis
on the
against the background of viral hepatitis C is also characterized
by fatty dystrophy.
Biliary cirrhosis (primary, secondary)

121
The liver is enlarged, dense, dark green in color, with a finely

nodular surface.
Significant enlargement of periportal fields with fibrosis around

proliferating cholangioles, intravalvular fibrosis around
intravalvular cholangioles with dissociation of hepatocytes and
formation of false lobules. Intravalvular and periportal
cholestasis.
• hepatic coma;
• bleeding from dilated esophageal veins;
• ascites-peritonitis;
• portal vein thrombosis;
• liver cancer
► CANCER OF THE LIVER◄
Liver cancer (hepatocellular carcinoma) is the most common

primary malignant tumor of the liver.
ETHIOLOGY
• chronic viral hepatitis B and C (about 86% of all cases);
• cirrhosis of the liver;
• Regular ingestion of hepatocarcinogens (e.g. aflatoxins);
• other causes - hemochromatosis; schistosomiasis and other parasitic
liver diseases; exposure to carcinogenic substances (polychlorinated
biphenyls, chlorinated pesticides, chlorinated hydrocarbons,
nitrosamines, etc.).
There are 3 main forms of hepatocellular carcinoma:
• knotty;
• massive;
• diffuse-infiltrative (more common in children).
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Nodular forms of the tumor are represented by one or more

nodules of pale brown or greenish color, the mass of the liver is
significantly increased. In the nodular form, the liver is lumpy,
in the diffuse form
carcinoma of the liver is stony dense.
In most cases, the tumor has a trabecular structure. Tumor cells

are larger than normal hepatocytes, with abundant cytoplasm
with pronounced eosinophilia. Tumor hepatocytes form a
and trabeculae. Foci of necrosis and hemorrhage are often seen
in the tumor parenchyma.
Metastasis of liver cancer is lymphogenic to the lymph nodes of the

liver gate and peritoneum; hematogenous (in 50% of cases) to the lungs and
bones. Metastases, like the main tumor, are greenish in color.
The cause of death is more often hemorrhage from decaying tumor
nodules or liver failure.
BILIARY TRACT DISEASES AND GALLBLADDER

DISEASES
The most important in clinical practice are

inflammation of the gallbladder (cholecystitis) and gallstone disease.
► CHOLECISTITE◄
Cholecystitis is an inflammation of the gallbladder.
ETHIOPATOGENESIS
In the occurrence of inflammation in the wall of the gallbladder is
important several factors, leading among which are:
• bacterial infection - microorganisms can penetrate into the gallbladder
from the duodenum (ascending route), as well as hematogenous or
lymphogenous from other foci of chronic infection;
• bile stasis:
- biliary dyskinesia;
- congenital deformity of the gallbladder outlet or bile ducts;
- violation of neuro-reflex regulation of the sphincter apparatus;
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- inflammatory changes в area phaternal

nipple (duodenitis);
-previously formed stones;
- tumors;
- pregnancy;
-low-mobility lifestyle, etc.
CLASSIFICATION
Figure 33. Classification of cholecystitis.
Acute catarrhal cholecystitis.
Gallbladder is slightly enlarged, its mucous membrane is
hyperemic, swollen, bile in the bladder cavity is watery, turbid
with an admixture of mucous-serous or
mucopurulent exudate.
Gallbladder wall is full blooded, edematous, in the mucosa and

submucosa infiltration with leukocytes, lymphoid cells,
macrophages is noted.
desquamation of epithelial cells.
Chronic catarrhal cholecystitis.

Gallbladder wall is thickened, sclerosed; mucosa is atrophied. In
some places can
polyposis overgrowths.
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A large number of macrophages containing cholesterol

(xanthoma cells) appear under the epithelium - cholesterosis of
the gallbladder. Lymphocytic and plasmocytic infiltrates. In the
period of relapse against the background of chronic changes
develop hyperemia, edema,
leukocyte infiltration.
Acute suppurative cholecystitis and other types of acute cholecystitis

Gallbladder is enlarged, tense; serous coverings are dull,
covered with fibrinous deposits (pericholecystitis), gallbladder
wall is sharply thickened (up to 0.5-1 cm). The mucous
membrane is swollen, full bloody, with erosions, ulcerations. In
the gallbladder lumen
accumulates purulent exudate colored with bile.
Purulent cholecystitis is more often phlegmonous, with

abundant diffuse infiltration of the gallbladder wall with
segmented leukocytes (phlegmonous cholecystitis). Often in
purulent cholecystitis there is necrosis of the mucosa with the
formation of more or less extensive ulcers (phlegmonous-
ulcerous cholecystitis). cholecystitis),
sometimes necrotized
mucosal tissues are abundantly impregnated with fibrinous
exudate and take the form of dirty-green films. These films are
rejected, and deep ulcers are formed in their place (diphtheritic
cholecystitis) or necrotic process extends to the entire thickness
of the gallbladder wall, which becomes black-brown, dull,
flabby
(gangrenous cholecystitis).
Chronic suppurative cholecystitis.

The gallbladder is deformed, reduced in size and fused with
neighboring organs by rough adhesions. The wall is
significantly thickened, dense due to sclerosis.
Internal surface of the gallbladder with fibrous tracts; mucosal
ulcers of varying depth may be present.
Against the background of sclerosis, infiltrates of lymphoid and

plasma cells are found in the gallbladder wall, a small amount
of
macrophages, eosinophilic leukocytes. Processes
125
reparations in chronic cholecystitis are expressed

in the form of granulation of ulcers with their
subsequent scarring
and epithelialization.
• Gallbladder empyema (develops as a result of bacterial
infection);
• formation of vesiculo-intestinal fistula. It develops as a result of
eating and breakthrough of a concretion through the wall of the
gallbladder into neighboring organs (most often into the
duodenum), and biliary obstruction of the intestine may occur;
• Emphysematous cholecystitis (develops in 1% of cases as a result
of multiplication of gas-forming microorganisms);
• sepsis;
• pancreatitis;
• Gallbladder perforation (develops in up to 15% of patients).
► GALLSTONE DISEASE◄
Gallstone disease is a disease in which there is stone formation in

the gallbladder and less commonly in the bile ducts.
ETHIOPATHOGENESIS
Several factors play a role in the occurrence of gallstone disease:
• hereditary predisposition - the disease occurs in many members of the
same family, especially in the female line, in different generations;
• overnutrition;
• the disease is more common in women, in old age. Three factors
are important in the pathogenesis of stone formation:
• metabolic disorders - as a result of metabolic disorders decreases the
level of bile acids in the bile, normally preventing the precipitation of
cholesterol from the bile in the sediment;
• stagnation of bile - anatomical changes in biliary tracts, functional
disorders associated with irregular nutrition, as well as neurogenic
factors can cause bile stasis;
126
• infection - infection and associated inflammation play a leading role in

stone formation, as the decaying gallbladder epithelium is a source of
cholesterol, and from the inflammatory exudate precipitates lime - the
second constituent of stones.
There are three stages in the development of gallstone disease:
• Stage I - the bladder wall is infiltrated with lipids, no stones;
• Stage II - microlithiasis (sand);
• III stage - formed stones в gall bladder
and the occurrence of complications associated with them.
Inflammation may precede stone formation or develop sequentially as a complication
(calculous cholecystitis).
EXOCRINE PANCREATIC DISEASES

GLANDS
► PANCREATITIS◄.
Pancreatitis is inflammation of the pancreas.
A distinction is made between acute pancreatitis and chronic pancreatitis.
ETHIOPATOGENESIS
Pancreatitis:
• 70% of patients with destructive pancreatitis (pancreonecrosis) are
alcohol abusers;
• 20% are individuals who developed pancreatitis as a complication of
cholelithiasis.
Also causes of pancreatitis can include:
• poisoning;
• trauma;
• viral diseases;
• Infectious diseases, including Helicobacter pylori;
• fungal lesions;
• parasitic diseases: opisthorchiasis и other
worm infestations;
• sphincter of Oddi dysfunction;
127
• complications after surgery and endoscopic manipulations.

The pathogenesis of pancreatitis is based on degenerative and
inflammatory damage of the pancreas caused by various reasons. There is
autolysis of pancreatic tissue due to the impact of its own activated
proteolytic enzymes - an enzymatic-chemical process, to which secondary
infection may join.
According to the nature of the inflammatory process, the following forms
of acute pancreatitis are distinguished:
• serous pancreatitis;
• catarrhal pancreatitis;
• purulent pancreatitis.
• Serous pancreatitis - the pancreas is swollen,

matted, and pink in color;
• purulent pancreatitis - the gland is enlarged, flabby,
yellowish in color, full of blood, from the surface of
the incision flows turbid fluid.
• Serous pancreatitis - turbid swelling of epithelium and

edema of interstitial tissue with lymphocytic infiltrates;
• catarrhal pancreatitis - mucopurulent exudate in the ducts
with desquamation of epithelium and leukocytic
infiltration of interdollicular connective tissue and all
layers of the ducts;
• purulent pancreatitis - purulent impregnation of the
interstitial tissue of the gland or formation of the
abscesses in the pancreatic tissue.
The pathologic anatomy of chronic pancreatitis between exacerbations

consists of connective tissue overgrowth with atrophy of excretory and less
often incretory parenchyma. The exacerbation manifests as any form of acute
pancreatitis, but more often as serous or catarrhal pancreatitis.
Acute pancreatic necrosis (pancreonecrosis)

This condition is a special form of acute pancreatitis in which there is
autolysis of the pancreas by the enzymes produced in it - trypsin and lipase.
128
The pancreas is flabby, edematous, blood-soaked. Serous

hemorrhagic general or local peritonitis is observed. In the fatty
tissue of the abdominal cavity are found stearin spots or fat
necroses. In partial necrosis of the gland at the site of the focus
an abscess and then a cyst.
Necrosis foci with hemorrhagic impregnation phenomena. In

focal necrosis of the gland in the tissue, which has not
undergone autolysis, develops reactive
inflammation.
Early complications
• purulent complications:
-dilute peritonitis;
-abscesses of the abdominal cavity (subdiaphragmatic,
subhepatic, interintestinal, pelvic, etc.);
-abscess of the pancreas and omental pouch;
-parapancreatitis - retroperitoneal phlegmon;
-purulent paranephritis;
-liver abscesses;
-sepsis, etc;
• hepatic-renal failure;
• CCC dysfunction;
• thrombohemorrhagic and hemocoagulation disorders (early
hypercoagulation due to trypsin action, and later - hypocoagulation).
They can lead to acute myocardial infarctions, cerebral circulatory
disorders, pulmonary embolisms.
• gastrointestinal bleeding;
• intestinal obstruction, fistula;
• thrombosis of the portal system;
Late complications
• pancreatic cysts;
• pancreatic fistulas;
• diabetes.
129
► PANCREATIC CANCER PANCREAS◄
Pancreatic cancer is a malignant neoplasm originating from the

epithelium of the glandular tissue or ducts of the pancreas.
ETHIOPATOGENESIS
Pancreatic cancer is the 6th most common cancer in the adult
population. It affects mainly elderly people, men and women equally often.
Risk factors for pancreatic cancer include:
• alcohol consumption;
• smoking;
• an abundance of fatty and spicy foods;
• diabetes;
• cirrhosis of the liver;
Precancerous lesions include:
• pancreatic adenoma;
• chronic pancreatitis;
• pancreatic cyst.
Usually the tumor affects the head of the gland (50-60% of cases),
body (10%), tail (5-8% of cases). There is also a complete lesion of the
pancreas - 20-35% of cases.
CLASSIFICATION
The following forms of pancreatic cancer are distinguished
according to histologic features:
• adenocarcinoma;
• squamous cell cancer;
• cystadenocarcinoma;
• acinar cell cancer;
• undifferentiated cancer.
Adenocarcinoma is the most common, occurring in 80% of pancreatic
cancers.
Dense lumpy nodule of different sizes, without clear boundaries
with surrounding normal tissue; on section
white or light yellow tumor, with separate
130
with areas of decay, dense consistency.
The microscopic picture depends on the histological type of the

tumor (see above) and its degree of differentiation (highly,
moderately, and low-differentiated tumors). Common
microscopic features include tissue and cellular atypism,
infiltrating growth ( invasion), and lymphocytic
infiltration.
The first metastases are found in lymph nodes located immediately near the
head of the pancreas; hematogenous metastases occur in the liver and other
organs.
Death occurs from exhaustion, cancer metastasis, or attached pneumonia.
131
SECTION VI.
KIDNEY DISEASE
Renal diseases include a large number of diverse pathologic
conditions, both in terms of clinical manifestations and morphologic
changes.
Depending on what is involved in the pathological process (tubules,
tubules, renal interstitial tissue) distinguish:
• glomerulopathies - glomerulonephritis;
• tubulopathies are pathologies of the tubules;
• interstitial kidney disease.
When the kidneys are affected, there are a number of symptoms (renal
and extrarenal), which can be used to indirectly judge the morphologic
changes in renal tissue.
Renal Extrarenal
• pyuria; • edema;
• hematuria; • hypo- and dysproteinemia;
• Cylindruria; • hypertension;
• Leukocyturia (including pyuria); • hyperazotemia;
• bacteriuria; • anemia.
• oliguria.
► GLOMERULONEPHRITIS◄
Glomerulonephritis (GN) is an infectious-allergic or unspecified

disease based on bilateral diffuse or focal non-purulent
inflammation of the renal tubular apparatus with renal and
extrarenal manifestations.
In general, the development of glomerulopathies is due to the

interaction of immune antigen-antibody complexes. There may be a direct
antibody response against the tubular basal membrane or circulating and
complexes are deposited in capillaries and initiate an inflammatory reaction
by binding to complement. Antigen-antibody complexes deposited on
mesangial cells and basal membranes cause inflammation and mesangial
proliferation.
Exceptions are glomerulopathies due to vasculitis, amyloid deposition,
extracellular accumulation of plasma proteins, as well as vascular damage in
diabetes mellitus.
132
ETHIOPATOGENESIS
Among the etiologic factors of glomerulonephritis are the following:
• infections: streptococcus (!), malaria, tuberculosis, syphilis,
viral hepatitis B and C, cytomegalovirus infection, etc.;
• medicinal remedies: vaccines; preparations gold,
D-penicillamine, captopril;
• hypothermia ("damp cold"!);
• malignant neoplasms;
• food intolerances, chemical agents;
• secondary glomerulonephritis - against the background of systemic
diseases (SLE, systemic vasculitis).
Two major mechanisms can be identified as the basis for the

pathogenesis of most glomerulonephritis (see Figure 34).
Figure 34. Pathogenetic mechanisms of glomerulonephritis development.

133
Three major clinical syndromes are associated with renal tubular damage:
• Nephrotic;
• nephritic;
• slow-onset uremia.
Nephrotic syndrome results from increased glomerular filtration and is

manifested by:
• proteinuria >3-4g/day;
• edema (due to hypoproteinemia);
• hyperlipidemia (as a nonspecific liver
response to decreased plasma oncotic
pressure and decreased lipoprotein
catabolism).
This condition may contribute to the development of increased risk of

venous thrombosis, accelerated development of atherosclerosis, increased
frequency of infections due to loss of immunoglobulins with urine.
Nephritic syndrome is characterized by the following features:

• Hematuria (dark-colored urine due to
the presence of red blood cells);
• oliguria;
• arterial hypertension;
• Proteinuria up to 2 g/day;
• mild swelling.
The development of slowly developing uremia is associated primarily

with hyalinosis of the tubules on the background of chronic
glomerulonephritis. Microscopically, it is manifested by accumulation of
homogeneous eosinophilic material in the capillary wall and between
capillaries, leading to narrowing and, over time, obliteration of their lumen.
CLASSIFICATION
There are large number of classifications
of glomerulonephritis:
• depending on the etiologic factors:
- primary glomerulonephritis:
134
o acute diffuse proliferative glomerulonephritis;

o rapidly progressive glomerulonephritis;
o membranous glomerulonephritis;
o lipoid nephrosis;
o focal segmental glomerulosclerosis;
o Membranous proliferative glomerulonephritis;
o Berger's disease;
o chronic glomerulonephritis;
- secondary glomerulonephritis:
o systemic lupus erythematosus;
o diabetes;
o amyloidosis;
o Goodpasture's syndrome;
o periarteritis nodosa;
o Wegener's granulomatosis;
- hereditary glomerulonephritis:
o Alport syndrome;
o Fabry's disease;
• downstream:
- sharp;
-fast progressive (subacute);
- chronic;
• in relation to the vascular tubercle:
- intracapillary (process localizes в the vascular
tubercle);
-extracapillary (the process is localized in the lumen of the
Shumlansky-Bowman capsule with the formation of semilunars);
• by the nature of the inflammatory process:
- exudative;
- proliferative;
- mixed;
• depending on the extent of the process:
- diffuse;
- focal;
• on pathogenesis:
- Immunocomplex - the tubule is damaged by immune complexes
circulating in the blood;
- Antibody: the tubule is damaged by immune complexes formed in
situ (against components of the basal membrane or cell
components such as visceral epithelium);
- complementary;
135
-as a manifestation of the GST response.

• Morphologic classification of glomerulonephritis:
- diffuse intracapillary glomerulonephritis (acute
glomerulonephritis);
- extracapillary glomerulonephritis с half moons
(rapidly progressive glomerulonephritis);
- Morphologic variants of chronic glomerulonephritis:
o Glomerulonephritis with minimal changes;
o membranous nephropathy;
o mesangioproliferative glomerulonephritis;
o mesangiocapillary (membranoproliferative);
o focal segmental glomerulosclerosis;
o fibroplastic glomerulonephritis.
ACUTE GLOMERULONEPHRITIS
The development of this type of glomerulonephritis is more often
noted in childhood, but it is not an uncommon disease and adults under the
age of 40 years; more often men are ill.
ETHIOPATOGENESIS
In the occurrence of acute glomerulonephritis (synonym - diffuse
intracapillary), the main role is played by β-hemolytic streptococcus group A
- types 12, 4, 1, 49, so it is often called post-streptococcal
glomerulonephritis.
This disease is characterized by association with a streptococcal
infection (sore throat, otitis media, pharyngitis, scarlatina, pyoderma, etc.) 1-
3 weeks before the onset of renal symptoms. Formed in the human body
immune complexes (between antigens and antibodies), are deposited on the
basal membrane of the capillaries of the tubules, followed by complement
fixation and activation, leading to the development of damage, inflammation
and cell proliferation.
CLINICAL MANIFESTATIONS
The acute onset is characterized by an increase in body temperature,
nausea, malaise. There is a rapid development of nephritic syndrome:
oliguria appears, dark urine (the color of "meat slop" due to the development
of hematuria). The appearance of mild hypertension and facial edema is
noted.
Duration of acute glomerulonephritis from 1.5 to 12 months (more
often 3 months). Protracted course - up to 1 year.
The prognosis is most often favorable: recovery is noted in almost 90% of
patients.
136
Acute poststreptococcal glomerulonephritis is not thought to progress to

chronic glomerulonephritis. Acute glomerulonephritis of non-streptococcal
etiology may become chronic in 10-20% of cases.
Clinical variants of acute glomerulonephritis

• nephritic syndrome
-edema , shortness of breath, headache, nausea, vomiting, weakness;
-arterial hypertension;
- hematuria;
-↓ diuresis;
- ↓ clubular filtration;
-↑ azotemia (in severe cases).
• with isolated urinary syndrome
-recurrent painless hematuria;
- oliguria;
- proteinuria;
- leukocyturia;
- cylindruria.
• with nephrotic syndrome (rare)
- hyperlipidemia;
-severe proteinuria;
- hypoproteinemia;
-explicit edema.
Acute (poststreptococcal) glomerulonephritis is characterized by
deposition of immune complexes under the epithelium and in the mesangium
in the form of electron-dense deposits (deposits) in the form of a "dome" on
the epithelial side of the basal membrane (so-called subepithelial "humps").
"mottled kidneys" - kidneys are enlarged in size, flabby

consistency with pronounced red mottling on a relatively
smooth surface, with wide ( on the
section) and full-blooded cortical substance
The tubule is enlarged, capillary loops are swollen, the so-

called "hypercellularity of the tubule" is noted (due to
proliferation of mesangial and endothelial cells of the vascular
tubule, infiltration of the
tubule).
polymorphonuclear leukocytes, as well as
137
proliferation of epithelial cells of the outer leaflet of the

Shumlansky-Bowman capsule). Capillary lumen is narrowed
due to pronounced edema and swelling of endothelial cells.
Immune complexes can be detected in the form of
characteristic "clumps".
When immunofluorescence is used, granular deposits of IgG
and C3 are detected along the course of the basal membrane of
the tubule and in the mesangium.
CONCLUSIONS.
• pulmonary edema;
• eclampsia (convulsive syndrome on the background of cerebral
edema);
• acute renal failure;
• Visual disturbances (edema, retinal detachment)
RAPIDLY PROGRESSIVE (SUBACUTE) GLOMERULONEPHRITIS

Rapidly progressive glomerulonephritis (subacute, malignant,
extracapillary proliferative,
glomerulonephritis with half-moons) is accompanied by the formation of
cellular, and at later stages - fibrous half-moons in more than 50-70% of
renal tubules.
The duration of the disease is short, averaging 6 months to 1.5 years.
ETHIOPATOGENESIS
The etiologic factors of this type of glomerulonephritis can be divided
into three groups:
• post-infection (post-streptococcal, etc.);
• in systemic diseases (Goodpasture's syndrome, nodular
periarteritis, systemic lupus erythematosus, Wegener's
granulomatosis, etc.);
• Idiopathic (more common than others).
The pathogenesis is based on immunocomplex or antinuclear damage

to the basal membranes of the capillaries of the tubules with a violation of
their permeability and subsequent inflammatory-proliferative reaction
(reactive proliferation of cells of the parietal sheet of the capsule of the
vascular tubule with the formation of so-called "half-moons"). With the
passage of time, the cell semilunar cells are replaced by connective tissue
with the formation of fibro-epithelial, and later on -
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of fibrous semilunaria. Compression of the vascular tubercle by the

semilunae eventually leads to the death of the tubercle.
Rapidly progressive glomerulonephritis is characterized by
proteinuria, edema, hematuria and hypertension. Without treatment, the
disease ends, after 6-18 months from the onset of the disease, with the
development of uremia or death of the patient may be associated with the
emergence of complications from the cardiovascular system (cerebral
hemorrhage, cardiovascular failure, etc.).
Diagnostic criteria:
• malignant arterial hypertension;
Clinical
• nephrotic or urinary syndrome;
• increase in serum creatinine ≥200
Laboratory μmol/L per month (or 2-fold for every 3
months);
• antibodies to the basal membrane of the tubules;
• antibodies to leukocyte cytoplasm (ANCA), to
Immunological
DNA;
• ↓ complement
A pattern of intra- or extracapillary glomerulonephritis is noted in the
kidney tissue.
Kidneys are sharply increased in size, weighing up to 300-500
g (normal 120-150 g). The surface is fine-grained, pale, often
with petechial hemorrhages on the surface, flabby consistency.
On section: cortical layer is broad (thickened), swollen, pale
yellow-gray, dull, with red mottling and well delimited from
the dark red brain matter of the kidney ("big mottled kidney"),
or red and merged with full-blooded pyramids ("big red
kidney").
Intracapillary glomerulonephritis.
A sharp increase in the size of the tubules due to proliferation
of podocytes, endothelial cells, mesangial cells, macrophages
with an admixture of leukocytes and their accumulation in the
vascular part of the tubule.
Thickening and deformation of capillary walls,
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damage and deformation of basal membranes.

Extracapillary glomerulonephritis
Proliferation of capsular epithelium, podocytes, macrophages
with their accumulation outside the vascular part of the tubule
with the formation of "half-moons". Capillaries of the tubule
undergo necrosis, and fibrin thrombi are seen in their lumen.
Displacement of capillaries of the vascular tubercle to the base
with their subsequent atrophy and sclerosis.
Epithelium of proximal and distal tubules with signs of protein

dystrophy of varying severity. The renal stroma is moderately
edematous, with areas of full blood vessels and hemorrhages.
Changes in other organs are characteristic of hypertension:

hypertrophy of the left ventricle with an increase in its mass and wall
thickness, arteriolosclerosis in the kidneys, brain and other organs.
CONCLUSIONS.
• acute or chronic renal failure;
• hemorrhages associated with arterial hypertension.
CHRONIC GLOMERULONEPHRITIS
Chronic glomerulonephritis is characterized by primary lesions of the

tubules and secondary involvement of tubules and stroma in the pathological
process.
Depending on the clinical and laboratory data, the following forms of
chronic glomerulonephritis are distinguished:
• latent form (most common)
-no complaints, urinary syndrome is often detected incidentally;
-proteinuria is slight (up to 1 g/day) or moderate (1-3 g/day);
- microhematuria;
-from the onset of the disease to the development of signs of
CKD - 10-25 years.
• hypertensive form
-urinary syndrome is detected simultaneously with arterial
hypertension;
-proteinuria <1 g/day;
- hematuria;
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CKD - 20-30 years.
• hematuric form
-urinary syndrome with persistent hematuria, episodes of
macrohematuria;
-proteinuria is minor;
CKD - 30-40 years.
• nephrotic form
CKD - 8-15 years;
- massive proteinuria (>3-3.5 g/day);
- hypoproteinemia (<65 g/L);
-hypoalbuminemia (<30 g/L);
-hypercholesterolemia (>5.2 mmol/L);
- swellings
• mixed form
-nephrotic syndrome + arterial hypertension;
- hematuria;
-↑ azotemia at the height of nephritis activity;
-from the onset of the disease to the development of CKD - 2-10 years.
В depending on on morphologic pattern chronic
glomerulonephritis is divided into:
• mesangioproliferative;
• membranous;
• Membranoproliferative or mesangiocapillary.
Kidneys are light gray-brown, reduced in size, shriveled

("secondary shriveled kidney"), the surface is fine-grained,
dense consistency. On
section - thinning of cortical substance and pyramids; when
cut, they are dry, dense, low-blooded.
Atrophy, sclerosis, and hyalinosis of capillary loops and the

whole tubule. The lumen of tubules is somewhat dilated,
epithelium with signs of protein dystrophy. Arterioles with
signs of sclerosis and hyalinosis of the walls.
Renal stroma with signs of sclerosis and diffuse focal
inflammatory infiltration.
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The formation of changes in organs and tissues is associated with the

presence of arterial hypertension. Thus, hypertrophy of the left ventricle of
the heart, arteriolosclerosis of retinal vessels, cerebral vessels and other
organs can be observed.
CONCLUSIONS.
• Nephrotic crisis (hypovolemic shock);
• thrombosis of peripheral veins and arteries, renal veins, TELA;
• cerebral hemorrhage;
• cardiovascular failure;
• infections (viral, bacterial);
• less often - azotemia, uremia, DIC.
GLOMERULONEPHRITIS WITH MINIMAL CHANGES (LIPOID NEPHROSIS)
Glomerulonephritis with minimal changes (idiopathic nephrotic

syndrome) - this renal pathology is most often observed in childhood (up to 8
years of age - approximately 80%) and rarely affects adults. Synonym -
"lipoid nephrosis", as fat droplets or cholesterol are found in the cytoplasm
of the tubule epithelium.
ETHIOPATHOGENESIS
The pathogenesis is based on a decrease in heparan sulfate
(proteoglycan) content in the basal membrane of the capillaries of the
tubules, which leads to a decrease in the negative charge in the membrane.
As a consequence, the filtration barrier becomes permeable to plasma
proteins, large amounts of which begin to be detected in the urine. This leads
to massive proteinuria, primarily due to the loss of albumin - so-called
"selective" proteinuria. The cause of chemical changes in the membrane is
unknown (idiopathic condition).
Clinically, lipoid nephrosis manifests with nephrotic syndrome (see

above) without arterial hypertension or hematuria.
Lipoid nephrosis is characterized by minimal changes in the
glomerular apparatus, which is manifested by the loss of podocytes of their
small outgrowths.
Minimal changes - microscopic (light-optical) changes of the tubules
are extremely minor, a n d , accordingly -
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are uninformative for diagnosis without the use of additional methods, such
as electron microscopic examination, which in this pathology become the
main.
Transmission electron microscope study reveals fusion of small
outgrowths of podocytes, their "adhesion" to the basal membrane, sclerosis
and mesangium enlargement.
Kidneys are enlarged in size, flabby consistency, the capsule is
thin, translucent, easily removable, the surface of the kidney is
smooth, yellowish in color. On the section the division into
cortical substance and pyramids is clear; expansion of cortical
layer is noted, it is yellow-white in color
or pale gray, pyramids grayish-red (so-called "large white
buds").
The tubules look practically unchanged - only very slightly

expressed thickening of the basal membrane and mesangium
dilation are noted.
Epithelial cells of proximal tubules look swollen, enlarged in
size, with signs of hyaline-droplet dystrophy. Cells contain
neutral fats, cholesterol in their cytoplasm. The lumen of
tubules is dilated; in the lumen - a large number of cylinders
(granular, hyaline). The renal stroma is edematous, full blood,
dilation of the lumen of lymphatic vessels is noted. The
interstitium contains a large
the amount of lipids, macrophages, lipophages.
CONCLUSIONS.
In older age, nephrosclerosis and chronic renal failure may develop.
► ACUTE RENAL FAILURE (OPN)◄
The morphologic equivalent of the clinical manifestations of acute

renal failure is necrosis of the epithelium of the proximal and sometimes
distal tubules of the kidneys so-called "necrotic nephrosis" (acute
tubulonecrosis of the kidney).
ETHIOLOGY
• prerenal causes:
-hypovolemia (bleeding, vomiting, diarrhea, burns,
inadequate diuresis);
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-renal hypoperfusion (abdominal aortic aneurysm, renal

artery stenosis/occlusion, hepatorenal syndrome;
-hypotension (cardiogenic shock, shock of various etiologies);
-edema syndrome (heart failure, liver cirrhosis, nephrotic
syndrome);
• Renal causes:
-clubular lesions;
-interstitial nephritis;
-damage to the tubules;
-vascular lesions;
• postrenal causes:
-Internal causes (stone, blood clot, papillary necrosis, urethral
stricture, prostatic hypertrophy or tumor, bladder tumor, radiation
fibrosis);
-External causes (pelvic tumor,
retroperitoneal fibrosis).
STUDIES OF OPN
• Initial stage (1-3 days) - manifestations of OPN itself are masked by
the clinic of the disease that caused OPN (shock, sepsis, poisoning);
• oliguric stage - occurs 1-3 days after the action of the pathological
factor. Duration, as a rule, about 1-2 weeks. It is characterized by the
appearance of oligo- and anuria, edema, nonspecific signs of
intoxication (weakness, lethargy, drowsiness, lethargy, loss of
appetite, nausea, vomiting), some patients may have heart rhythm
disturbances, increased blood pressure;
• Diuresis recovery stage - with a favorable course of the disease on the
5-10 day there is a gradual increase in the volume of excreted urine;
• recovery stage - full recovery of kidney function may take up to 1 year
or more.
Kidneys are enlarged in size, flabby consistency, smooth outer
surface, fibrous capsule is tense, easily removable. On the
section the cortex is enlarged, pale, in some places with red
mottling, pyramids
full-blooded, on the border of the cortex and pyramids is noted
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the presence of a cortico-medullary shunt.
The structure of the tubules is preserved. Epithelial cells of

proximal tubules (in some cases also distal tubules) are
enlarged in size, with indistinct boundaries, often with
destroyed apical pole (plasmarexis). In the epithelium of
proximal tubules nuclei are absent (karyolysis), or visible in
the form of "shadows". Edema of the renal stroma. At late
stages - alternation of areas of necrosis of tubule epithelium
with islets of regeneration in the form of light epithelial cells.
cells, sclerosis foci form.
► PIELONEFRITIS◄
Pyelonephritis is an inflammatory disease of the calyx and
tubulo-interstitial tissue of the kidneys.
Pyelonephritis is the most common disease in nephrological practice

and accounts for up to 60% of all kidney diseases. They are often (about
40% of cases) the cause of chronic renal failure.
ETHIOLOGY
Pyelonephritis has a predominantly infectious etiology and is most
often caused by Escherichia coli, as well as when entering the urinary tract
of enterococci, proteus, strepto- and staphylococci, mycoplasmas,
leptospires, fungi and others.
Predisposing factors:
• gender - 2-3 times more common in women (women have shorter
and wider urethra);
• Hormonal imbalance: glucocorticoids and hormonal
contraceptives;
• metabolic disorders: diabetes mellitus, gout;
• kidney and urinary tract anomalies;
• hypothermia.
Pathways of infection:
• Hematogenous or lymphogenous (descending);
• Urinogenic (ascending) is more common.
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CLASSIFICATION
Figure 35. Classification of pyelonephritis.
According to the course, acute and chronic pyelonephritis are distinguished:

• rapidly progressive;
• recurrent - almost 80%; alternating exacerbations and
remissions are characteristic;
• latent - 20% of patients; most often there are no complaints. There
may be increased fatigue, weakness, in some cases - subfebrile.
Diagnosis is made laboratory (leukocyturia, moderate proteinuria,
bacteriuria).
ACUTE PYELONEPHRITIS
Acute pyelonephritis is characterized by the so-called "classic triad":

fever, dysuria, low back pain.
Clinical manifestations:
- severe chills;
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- an increase in body temperature of up to 40°C;

- pouring sweat;
- pain in the lumbar region (on one side or both sides of the spine);
- on the side of the affected kidney - tension of the anterior abdominal
wall;
- sharp soreness in the rib-vertebral angle;
- symptoms of severe intoxication -
general malaise, thirst, nausea, vomiting, dry
mouth, muscle pain;
- dysuric manifestations.
Acute pyelonephritis can be either bilateral or unilateral.
Kidneys are enlarged in size, thickened. In the cortex and
pyramids - various sizes of cavities with greenish-gray semi-
liquid contents (abscesses). In the lumen of the calyx and
pelvis contains cloudy urine or greenish-gray semi-liquid
content (pus). In hematogenous (descending) pyelonephritis,
abscesses are located diffusely, predominantly in the upper,
and
in case of urinogenic (ascending) infection - in the lower pole
of the kidney.
In the lumen of collecting tubes - accumulations of

neutrophils; edema, fulminant hemorrhage and pronounced
diffuse focal leukocytic infiltration of interstitium in the area
of calyxes and walls of the pelvis. Areas of necrosis,
hemorrhages.
During healing, in place of areas of necrosis, in the area of
inflammation there is a development of connective tissue, and
the inflammatory infiltrate begins to be dominated by
lymphocytes and plasmocytes.
Pyonephrosis
The kidney is enlarged in size, but thinning of the cortex
(atrophy) and pyramids is noted on the section. There is a
sharp enlargement of the calyx and pelvis, which are filled
with pus.
CONCLUSIONS.
• Necrosis of the renal papillae (papillonecrosis) - necrotized
papillae fall off into the lumen of the pelvis. This complication
147
is most common in diabetics;

• apostematous pyelonephritis - multiple small abscesses;
• carbuncle of the kidney;
• Pyonephrosis - more often develops with high ureteral obstruction
(at the border with the kidney) or carbuncle rupture;
• sepsis;
• paranephritis (inflammation of the perianal tissue);
• Perinephritis (inflammation of the fibrous capsule);
• perirenal abscess
CHRONIC PYELONEPHRITIS
Among the causes of chronicization should be noted: disorders of

urodynamics, focal infection, inadequate treatment of acute pyelonephritis.
For many years, it can be latent (without symptoms) and is detected
only by urine examination (latent period, remission period).
Clinically manifested by dull constant pain in the lumbar region on the
side of the affected kidney.
Chronic pyelonephritis is characterized by variegated morphological
manifestations, as exudative-necrotic processes are combined with sclerotic
changes.
Kidney involvement is usually asymmetric. The size of the
kidney is variable, the surface is coarsely lumpy, the
consistency is dense, the capsule is thickened, removable with
difficulty. On the section - areas of connective tissue
overgrowth (scarring) alternating with preserved renal
parenchyma, thickening of the wall of the pelvis is noted. In
the cortex and pyramids there can be found cavities of various
sizes with greenish-gray semi-liquid content (abscesses). In the
lumen of the calyx and pelvis contains turbid urine or greenish-
gray semifluid content ( pus). Deformity is often observed
of the calyx.
In the lumen of collecting tubes - accumulations of

neutrophils, the epithelium of tubules undergoes dystrophic-
atrophic changes. The tubules
expand, the epithelium flattens, the lumen of part of the
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distal tubules and collecting tubes are filled with colloid-like

content - "thyroidization of the kidney" ("thyroid kidney").
Around the tubules - periglomerular and extracapillary
glomerulosclerosis. In the area of calyxes and pelvis - edema,
full blood vessels and diffuse focal leukocytic
infiltration.
In exacerbation of chronic pyelonephritis, the same symptoms are

observed as in acute pyelonephritis, and the histological picture is
manifested by pronounced leukocytic infiltration and hemorrhage on the
background of sclerosed renal tissue with atrophic tubules.
The outcome of chronic pyelonephritis is the formation of
"pyelonephritic secondary shriveled kidneys". Complications:
• chronic kidney abscess;
• nephrogenic arterial hypertension;
• uremia (chronic renal failure) - in about 15% of patients.
► CHRONIC RENAL FAILURE

(CKD)◄
Chronic renal failure (azotemic uremia) is characterized by an increase

in the blood concentration of nitrogenous slag, which is mainly due to a
sharp decrease in the number of functioning nephrons. The consequence is a
violation of: excretory and incretory function of the kidneys, metabolism,
acid-base balance, the activity of all organs and systems of the human body.
Uremia is a syndrome consisting of autointoxication of the body by
metabolic products (normal and disturbed), "uremic toxins" and exogenous
compounds normally excreted by the kidneys.
ETHIOPATOGENESIS
• diseases with primary damage to the tubules - chronic
glomerulonephritis, subacute glomerulonephritis;
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• diseases with primary lesions of tubules and interstitium - chronic

pyelonephritis, interstitial nephritis, radiation nephritis, Balkan
nephropathy;
• obstructive nephropathies - urolithiasis, hydronephrosis, urogenital
tumors;
• Primary vascular lesions - malignant hypertension, renal artery
stenosis, hypertension;
• diffuse connective tissue diseases - systemic lupus erythematosus,
scleroderma, periarteritis nodosa, systemic vasculitis;
• metabolic diseases - diabetes mellitus, amyloidosis, gout;
• Congenital kidney diseases - polycystic kidney disease, renal
hypoplasia, Fanconi syndrome, Alport syndrome.
The kidney, with increasing pathological changes in the nephrons,

practically ceases to perform its excretory function. However, the body
needs to get rid of toxic decomposition products. In this regard, this function
is assumed by other, not intended for the excretion of toxic products,
excretory organs: skin, mucous membranes of the GI tract, serous
membranes. This leads to damage to the body systems "uremic toxins" with
the development of appropriate clinical symptom complexes.
CLINICAL AND MORPHOLOGIC MANIFESTATIONS OF CHF
Skin:
• pale, yellowish skin color (due to accumulation of
urochrome in it);
• dry, flabby skin;
• facial puffiness;
• "powderiness" of the skin (urea and uric acid crystals);
• rash, scabies, especially on the legs, due to itching,
subcutaneous hemorrhages.
Cardiovascular system:
• hypertension, increased heart size;
• myocardial dystrophy;
• uremic myocarditis;
• fibrinous pericarditis;
• on ECG: arrhythmias, tendency to bradycardia, but
sometimes tachycardia;
150
• Heart failure - often accompanies CKD and significantly

worsens the prognosis.
Respiratory System:
• Cough (uremic laryngitis, tracheitis, pneumonitis);
• fibrinous pleurisy;
• Choking attacks, up to cardiac asthma, due to uremic
pulmonary edema;
• tendency to infection (bronchitis, pneumonia).
Digestive System:
• nausea, vomiting, thirst;
• pharyngitis, mumps, stomatitis;
• uremic gastritis, ulcerative lesions, bleeding;
• anorexia, weight loss;
• peritonitis;
• fatty degeneration of the liver.
Nervous System:
• malaise, headache, meningismus, insomnia or drowsiness,
emotional lability, apathy, impaired hearing, taste;
• impaired memory and thinking, labored speech, tremors, seizures,
stupor, coma;
• Peripheral nerve damage - symmetrical sensorimotor polyneuropathy
(burning pain in the feet and shins, muscle weakness, up to paresis
and paralysis);
• toxic effect of uremic poisons (ammonia, indole, scatol) on the brain
- headaches, twitching of certain muscle groups;
• in severe cases, apathy ("silent uremia");
• Eclampsia (associated with increased intracranial pressure) ("noisy
uremia").
The sexual system:
• amenorrhea, impotence, gynecomastia;
Musculoskeletal system:
• Radiologically - osteoporosis (associated with calcium loss);
• osteomalacia;
• secondary hyperparathyroidism.
In addition, the following syndromes develop in CKD:

• Anemia (normochromic, normocytic anemia
[hypoplastic]) by cause:
-the absence of erythropoietin;
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-Effects of uremic toxins on bone marrow;

-Effects of an inhibitor of erythropoiesis;
-hemolysis of red blood cells;
-bleeding and hemorrhage (decreased platelet count, impaired
platelet aggregation and adhesion, decreased prothrombin and
platelet factor III activity, increased bleeding time).
• Arterial hypertension (causes):
-Renin hyperproduction;
-Reduced formation of depressor prostaglandins;
-decreased sodium excretion;
-increased volume of extracellular fluid.
• Renal osteodystrophy (causes):
- decreased formation of the active form of vitamin D3;
- reduction of Ca absorption in the intestine;
- Club acidosis (exchange of Ca2+ and Na+ ions for H+ ions in the blood;
as a consequence, hypocalcemia occurs);
- decreased phosphate excretion → hyperphosphatemia → hypocalcemia
→ stimulation of parathyroid glands → bone resorption.
The cause death of the patients is by
increasing organ and system failure.
► UROLITHIASIS DISEASE◄
Urolithiasis (urolithiasis) is a chronic disease in which stone

formation occurs at any level of the urinary system, from the
urinary tubules to the bladder.
Urolithiasis (urolithiasis) accounts for 30-45% of all urologic diseases.

Most commonly, stones form in the kidneys, and in 1% of cases they may be
an incidental finding at autopsy of a deceased person.
ETHIOLOGY
Urolithiasis is a polyetiologic disease. It can be caused by:
• Enzymopathies (tubulopathies) with impairment in distal and proximal
tubules;
• climatic conditions (ambient temperature, humidity, mineral
composition of water - lead to stone substrate concentration);
152
• urinary outflow obstruction of various etiologies;

• hyperfunction of the parathyroid glands;
• vitamin and micronutrient deficiencies;
• hormonal disorders;
• changes in urine pH;
• inflammatory processes, etc.
CLASSIFICATION
The chemical composition of stones is different and heterogeneous
even in the same stone. When calling a stone urate, oxalate, phosphate, etc.,
they mean the predominant chemical component in the stone.
- oxalates - consist of calcium salts of oxalic acid, very dense, the surface
is lumpy, spiky. The natural color is gray, but they easily wound the
mucous membrane, and blood pigment stains them black;
- Urates - consist of uric acid or its salts, colored yellow in various
shades; consistency is hard, the surface is smooth or granular;
- Phosphates and carbonates - consist of salts of phosphoric and carbonic
acids, grayish-white color, surface rough, consistency loose,
crumbling;
- cystine stones - almost colorless, surface shiny, consistency dense;
- xanthine stones - reddish color, smooth surface.
The so-called "coral-like" stones resemble the branching structure of a
coral. This is a consequence of the fact that these stones repeat the shape of
the calyx of the kidney.
The main symptoms of urolithiasis are pain in the lumbar region,
hematuria, discharge of salts and stones with urine. Pain increases with
movement and excessive fluid intake. Acute pain, known as renal colic, may
occur as a result of blockage of the upper urinary tract by a stone.
CONCLUSIONS.
• pyelonephritis;
• pyonephrosis;
• purulent melting of the kidney;
• sepsis;
• CKD with an outcome of uremia
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SECTION VII.
DISEASES WITH PREDOMINANT ENDOCRINE SYSTEM

INVOLVEMENT
The endocrine system ensures the maintenance of homeostasis by

means of hormones, which by chemical structure may be derived from
steroids, peptides or amino acids.
Common factors of etiopathogenesis of endocrine system diseases

The etiology and pathogenesis of endocrine system diseases are based
on the following congenital (including hereditary) and acquired mechanisms:
• hypofunction of the endocrine glands;
• hyperfunction;
• secretion of an abnormal hormone, violation of the rhythm (circadian -
diurnal, seasonal, etc.) of hormone secretion;
• resistance or hypersensitivity of target organs and target cells to the
action of the hormone;
• Abnormalities of hormone transport and metabolism;
• multiple anomalies (combinations different mechanisms
of pathogenesis).
DISEASES WITH PREDOMINANT LESIONS OF THE PITUITARY GLAND

AND HYPOTHALAMUS
In the pituitary gland, inflammatory changes of various etiologies,
primarily viral, as well as necrotic changes caused by circulatory disorders
are possible. The most common types of pituitary and hypothalamic
pathology are atrophy (age-related, in myxedema, damage to the
intermediate brain), hyperplasia, and tumors.
Among the pathologies of the hypothalamus and pituitary gland, the
following disorders have the greatest clinical significance: (pan-)
hypopituitarism, hyperpituitarism, and pathology of antidiuretic hormone
associated with its insufficient secretion (nonsugar diabetes).
► HYPOPITUITARISM◄
Hypopituitarism is a pathological condition characterized by

partial or complete loss of function of the anterior lobe of the
pituitary gland.
154
Depending on the etiologic factor, the following types of

hypopituitarism are distinguished:
• primary hypopituitarism (primary lesion of the pituitary gland:
ischemic infarction, hemorrhage; hormonally inactive tumors and
tumor metastases; necrosis in neuroinfection, intoxication, metabolic
disorders; autoimmune hypophysitis; irradiation or surgery on the
pituitary gland; trauma, etc.);
• secondary hypopituitarism (hypothalamic pathology);
• Idiopathic hypopituitarism (cause not clarified).
The following should be emphasized as common clinical manifestations of

hypopituitarism:
• neurosomatic disorders (hypothermia, autonomic disorders, headache,
decreased vision and narrowing of visual fields);
• psychopathic disorders (apathy, depression, hallucinations, paranoid
psychosis);
• sexual dysfunction.
In addition, hypopituitarism can be total (panhypopituitarism) or partial

(partial). In case of total hypopituitarism, there is a deficiency of all
adenohypophysis hormones, while partial hypopituitarism is characterized
by a deficiency of any one hormone.
PANHYPOPITUITARISM
Panhypopituitarism (total hypopituitarism) - develops when 90%

of the adenohypophysis parenchyma is damaged and is
characterized by insufficiency of all adenohypophysis hormones.
В as diseases с panhypopituitarism are

Simmonds syndrome and Sheehan's syndrome.
Etiology
• massive blood loss;
• sepsis;
• shock;
• DIC;
• adenohypophysial thromboembolism.
155
Simmonds syndrome (cerebral-pituitary cachexia) is characterized by

postpartum total necrosis of the adenohypophysis with rapidly progressive
cachexia and the development of pituitary coma (acute adenohypophyseal
insufficiency, acute adrenal insufficiency, hypothyroid coma). Clinically
characteristic: sudden weight loss, premature aging, atrophy of internal
organs, thinning of the skin with wrinkles around the eyes, hair loss,
decreased hair growth in the axillae, pubic area, arterial hypotension, muscle
weakness.
Sheehan syndrome (postpartum hypopituitarism) is a condition that

develops as a result of massive postpartum hemorrhage and the development
of arterial hypotension (it is a type of Simmonds syndrome). During
pregnancy, the pituitary gland increases in size, and against the background
of decreased blood pressure, the blood supply to the pituitary gland is
impaired - hypoxia and necrosis of the pituitary gland develop.
Sheehan's syndrome is also called "7 "a syndrome":
• Amenorrhea;
• Agalactia;
• loss of Axillary hairline;
• depigmentation Areol;
• "Alabaster" pallor of the skin;
• Apathy;
• Adynamia.
Primary form of panhypopituitarism: infarction, hemorrhage,
toxic or metabolic necrosis, hormonally inactive tumors,
metastasis, inflammation, autoimmune lymphocytic
hypophysitis, fibrosis, atrophy from pressure from invagination
of the soft dura mater (in empty Turkish saddle syndrome) are
defined in the pituitary gland.
Secondary form of panhypopituitarism: atrophy of
adenohypophysis expressed in varying degrees, associated with
a decrease in the number of chromophilic cells. In peripheral
organs - "Simmonds' cachexia" (brown atrophy of myocardium,
liver, skeletal muscles), atrophy of endocrine glands and
lymphoid tissue, polyneuritis and
neurodystrophy, osteoporosis.
156
PARTIAL (PARTIAL) HYPOPITUITARISM

Of greatest clinical significance is a deficiency in somatotropic
hormone production, resulting in pituitary nannismus (dwarfism).
Pituitary nanism is a dysontogenetic syndrome characterized by

severe stunting and physical development associated with absolute
or relative STH deficiency.
Dwarfism is defined as a height of less than 130 centimeters for men and
less than 120 centimeters for women.
Highlight:
• pituitary nanism (primary pathology of the pituitary gland);
• hypothalamic nanism (deficiency of synthesis and secretion of
releasing factors);
• tissue resistance to the action of somatotropic hormone
at the target tissue level (receptor pathology).
MORPHOLOGICAL MANIFESTATIONS
• stunting since 2-3 years of age, dynamics of 1.5-2 cm per

year without treatment;
• lagging differentiation and ossification of the skeleton
from age, delayed change of teeth;
• "childlike" body proportions;
• skin pale, dry, with a bluish or yellowish tint, with the
symptom of "marbling". Early signs of aging;
• muscle hypotrophy;
• underdevelopment of the larynx - high
infantile timbre of voice;
• hypogonadism (in some cases).
► HYPERPITUITARISM◄
Hyperpituitarism is a hyperfunction of the pituitary gland that

develops due to hyperplasia of its glandular cells or tumor.
В depending on on hypersecretion of or one or another

There are several diseases and/or syndromes that can be
distinguished from hypersecretion of adenohypophyseal hormone,
157
The most important of which are gigantism/acromegaly and

Icenko-Cushing's disease.
GIANTISM
Gigantism is a very large stature occurring in individuals with

open epiphyseal growth zones (children and adolescents) with
excessive secretion of STH.
Clinically, the disease is manifested p r i m a r i l y b y tall stature

(women are taller than 190 cm and men are taller than 200 cm) with
proportional development of the skeleton. В first phase of the
disease, there is an increase in the volume of muscle, which в
later replaced by connective tissue overgrowth and muscle
weakness. Patients note deterioration of the general condition, headaches,
weakness, rapid fatigue, pain in the extremities. Muscle strength may be
increased at the beginning, but later sharply decreases. Hypogenitalism is
noted from the beginning of the disease. In women, there is primary
amenorrhea or early cessation of
menstruation, infertility. There may there can be и other
Hormonal disorders (symptoms of non-sugar diabetes,
hypo- or hyperthyroidism and
et al.).
Cardiomegaly, combined with high blood pressure. Increased
size of abdominal organs: stomach, liver, spleen, intestines.
Clinically present signs of digestive disorders, such as:
abdominal pain, constipation, abdominal bloating, heartburn,
frequent belching and others. Skin
the skin is thickened, and there are many facial folds.
ACROMEGALIA
Acromegaly is a disease associated with a disorder of the

adenohypophysis, accompanied by enlargement of the hands, feet,
skull (especially its facial part) due to excessive secretion of
somatotropic hormone.
Etiology
• Eosinophilic adenoma or adenocarcinoma of the pituitary gland:
growth of tissues, mainly derived from mesenchyme (bone, cartilage,
loose connective tissue) is stimulated;
• encephalitis.
158
MORPHOLOGICAL MANIFESTATIONS
Increased size of nose, ears, lower jaw, hands, feet; widening of
spaces between teeth. Heart failure; headaches; loss of
peripheral vision; diabetes mellitus; arterial hypertension;
seborrhea; atrophy of the sex glands; enlargement of distal
limbs; coarsening of facial features; enlargement of the
size of vertebral bodies, ribs; sharp thickening of the spongy
layer of bones.
COMPLICATIONS,
• cardiac OUTCOMES
insufficiency as a dilatational
cardiomyopathies; consequenc
• pulmonary failure; e
• secondary diabetes mellitus;
• increased risk of developing neoplasms of various organs.
ICENCO-CUSHING'S DISEASE
Icenko-Cushing's disease is a neuroendocrine disease

characterized by increased production of adrenal cortex
hormones, which is caused by excessive secretion of ACTH by cells
of hyperplasic or tumorous pituitary tissue (in 90% due to
microadenoma).
ETHIOPATOGENESIS
It develops most often in women aged 25-45 years. In most cases,
pituitary adenoma is detected. Macroadenomas occur in 10% of cases, the
rest are represented by microadenomas of the pituitary gland, which are
visualized only with the help of computed tomography. These patients have
a history of head contusions, concussion, craniocerebral trauma, encephalitis,
arachnoiditis and other CNS lesions.
The main clinical manifestations of the disease include:
• obesity (mainly of the upper type); the face becomes moon-shaped,
rounded, cheeks red (so-called "matronism");
• pink-purple or purple streaks (striae) on the skin;
• excessive body hair growth;
159
• Menstrual irregularities and infertility in women, and decreased sexual

desire/potency in men;
• muscle weakness;
• Bone fragility (osteoporosis), up to pathologic fractures of the spine,
ribs;
• arterial hypertension;
• impaired insulin sensitivity and the development of diabetes mellitus;
• pyelonephritis, urolithiasis;
• sleep disturbances, euphoria, depression;
• decrease in immunity with the formation of trophic ulcers, pustular
skin lesions, chronic pyelonephritis, sepsis, etc.
• Adenohypophysis - hyperplasia of basophilic adenocytes or basophilic
adenomas (microadenomas);
• Adrenal glands - diffuse nodular hyperplasia of fascicular and reticular
zones of the cortex;
• heart - myocardial hypertrophy and signs of steroid cardiomyopathy;
• Kidneys - primary wrinkled kidney + as a result of bone
decalcification and excretion of large amounts of calcium,
nephrocalcinosis develops and kidney stones form;
• other changes - fatty degeneration of the liver, osteoporosis,
hypotrophy of the sex glands, etc.
There are pathological bone fractures, diabetes mellitus and often associated
furunculosis, nephrosclerosis. Severe psychiatric disorders are possible.
Brain hemorrhage, cardiovascular failure, and sepsis as a result of decreased
resistance to infection are life-threatening.
► NON-SUGAR DIABETES◄
Non-sugar diabetes is a disease associated with absolute or

relative insufficiency of antidiuretic hormone, characterized by
polyuria and polydipsia.
160
ETHIOPATHOGENESIS
Non-sugar diabetes develops due to one of the pathologic processes:
• hypothalamic and/or pituitary tumors;
• The presence of metastases of malignant neoplasms in the brain
affecting hypothalamic and/or pituitary function;
• Pathology of the hypothalamic-pituitary system (disorders in the
hypothalamic-pituitary tract and blood supply to the hypothalamic
nuclei and posterior lobe of the pituitary gland);
• head trauma;
• inflammation, infections;
• familial (hereditary) forms of non-sugar diabetes;
• impaired perception of antidiuretic hormone by target cells in the
kidneys (primary tubulopathy).
CLASSIFICATION
• Central non-sugar diabetes (primary, neurogenic, hypothalamic-
pituitary) - absolute ADH deficiency:
- Congenital (genetic predisposition);
- acquired (traumatic, postoperative, etc.);
• nephrogenic (congenital and acquired): relative ADH insufficiency
due to impaired ADH receptivity in the kidneys in metabolic
disorders, hypoxia due to anemia, kidney disease, urinary tract
obstruction, etc.;
• dipsogenic (primary, nervous polydipsia): decrease in threshold of
thirst center activation in organic lesions of CNS thirst centers,
psychiatric disorders;
• idiopathic.
Increased urine output up to 5-6 liters per day, increased thirst,
nicturia, fatigue, sleep disturbance, headache, dry skin, weight
loss, stretching and
gastric prolapse, bladder distension, decreased blood pressure.
In the central form - dystrophy of hypothalamic neurons with

damage to membrane osmo- and baroreceptors of the thirst
center; tumors, vascular, inflammatory changes in the
hypothalamus, dystrophy, necrosis, atrophy of neurons. In the
kidneys - protein and fatty
dystrophy of the epithelium of the convoluted tubules,
inflammation
161
of various of various natures, atrophy of the

epithelium of the tubules и
of the collecting tubes.
ADRENAL DISEASES
Adrenal diseases cover a large group of pathological conditions of
different genesis, characterized by a variety of clinical and morphological
manifestations.
The following should be emphasized as the main etiological factors of
adrenal pathology:
• circulatory disorders, including massive hemorrhage in shock,
particularly infectious-toxic shock;
• dystrophic changes of various origins;
• Inflammatory damage by bacteria, more commonly Mycobacterium
tuberculosis, and viruses, especially adenoviruses;
• tumors.
The classification of adrenal pathology is summarized below in Fig.

36. Hypocorticism (acute and chronic) and various forms of adrenal cortex
hyperfunction associated with hyperproduction of hormones by the tubular,
fascicular or reticular zone of the adrenal cortex are of the greatest clinical
significance.
162
Figure 36. Classification of adrenal pathology.
► ACUTE ADRENAL INSUFFICIENCY (ACUTE

HYPOCORTICISM)◄
Acute hypocorticism - acute functional insufficiency of the

adrenal cortex in bilateral adrenal hemorrhage (Waterhouse-
Friederiksen syndrome), damage to the adrenal glands as a result
of trauma or surgery.
163
ETHIOPATOGENESIS
As a result of rapid destruction of the adrenal glands, for example, in
massive hemorrhages in the adrenal glands during birth trauma, asphyxia,
infectious diseases (most often meningococcemia), acute adrenal
insufficiency, incompatible with life, develops.
The etiologic factors may include:
• shock;
• DIC, coagulopathies;
• vasculitis, SLE;
• Bilateral adrenal hemorrhage (hemorrhagic infarction);
• bilateral adrenalectomy or removal of one
atrophy, hypoplasia or aplasia of the other adrenal
gland;
• acute intoxication;
• abrupt withdrawal of steroid therapy;
• acute hypothalamic-pituitary insufficiency.
Bilateral total (subtotal) necrosis or hemorrhages (hemorrhagic
infarction); primary or secondary atrophy. In addisonian crisis,
bilateral changes develop, corresponding to the cause of the
disease (tumor, tuberculosis, etc.) Other organs and
tissue: morphologic signs of shock.
► PRIMARY CHRONIC ADRENAL CORTEX

INSUFFICIENCY (ADDISON'S DISEASE)◄
Primary chronic adrenal cortical insufficiency (Addison's

disease, "bronze disease") is a chronic pathologic condition
caused by bilateral lesions of the adrenal cortex and decreased
production of adrenal cortical hormones.
ETHIOPATHOGENESIS
Addison's disease (primary chronic adrenal insufficiency) results from
destructive processes of various origins in the adrenal cortex itself. The most
common causes are:
• Hematogenous tuberculosis (up to 85% of cases);
164
• other causes: adrenal hemorrhage, vascular thrombosis, syphilis,

bilateral tumors or cancer metastasis to the adrenal glands,
amyloidosis, purulent inflammation of the adrenal glands,
lymphogranulomatosis, histoplasmosis, hemochromatosis, long-term
corticosteroid therapy, etc.
The underlying pathogenesis of Addison's disease is a shutdown or
dramatic decrease in the production of gluco- and mineralocorticoids
(cortisol, aldosterone, and corticosterone).
Clinical manifestations are associated with decreased cortisol

production and excessive secretion of ACTH. Gastrointestinal disorders are
characteristic: anorexia, nausea, constipation alternating with diarrhea.
Hypotension, adynamia, muscle weakness, gauntness and impaired water-
salt metabolism are constant symptoms.
Increased melanin formation accompanied by
hyperpigmentation of the skin (initially in the elbow folds) and
mucous membranes, brown atrophy of the myocardium,
narrowing of the lumen of the aorta and main vessels, atrophy of
the gastric mucosa, hyperplasia of the lymphoid tissue, and
of the thymus gland.
Pathologic changes in the adrenal cortex are mainly in the nature of

widespread destructive or atrophic changes:
• Destructive changes - due to the cause of chronic adrenal insufficiency
(tuberculosis, cancer metastases, hemochromatosis, etc.) and
manifested accordingly;
• Atrophic changes - marked decrease in adrenal mass due to a decrease
in the size and thickness of the cortex. Microscopically - significant
thinning of the cortical layer with disruption of the normal
architectonics of fascicular and reticular zones.
The most frequent and dangerous complication of Addison's disease is
hypoadrenal (Addisonian) crisis - acute adrenal insufficiency. This crisis can
be caused by acute infectious disease, mental and physical trauma,
165
pregnancy, childbirth, surgical intervention, etc. Clinical and morphologic

manifestations will correspond to acute adrenal insufficiency (see above).
► ADRENAL CORTEX HYPERFUNCTION◄
Given the presence of 3 functional zones in the cortex responsible for

the secretion of mineralocorticoids, glucocorticoids and sex hormones, the
following is a brief description of the main syndromes of adrenal cortical
hyperfunction of the 3 types: Icenko-Cushing syndrome, hyperaldosteronism
and virilizing syndromes.
Icenko-Cushing syndrome - develops against the background of primary

hyperplasia or tumor of the adrenal cortex and is manifested by
masculinization, obesity of the trunk, moon-shaped face, hyperpigmentation
of the skin on the neck, elbows. Hirsutism, arterial hypertension, polyuria,
development of diabetes mellitus, menstrual disorders in women and potency
in men, muscle weakness are also characteristic. Osteoporosis of bones of
the limbs, spine (up to the formation of "fish vertebrae"), accompanied by
spontaneous fractures.
Primary aldosteronism (Conn's disease) - aldosterone hypersecretion occurs

in tumors or hyperplasia of the adrenal cortex. Hyperplasia of the tubular
zone of the cortex, leads to the secretion of excessive amounts of aldosterone
and is manifested by arterial hypertension, hypokalemia, sodium retention in
the renal tubules, increased volume of extracellular and intravascular fluid,
edema of the vascular wall.
Congenital hyperplasia of the adrenal cortex (adrenogenital syndrome) is

an inherited deficiency of enzymes of glucocorticoid synthesis. The most
common is insufficiency of 21-hydroxylase, resulting in decreased cortisol
synthesis and increased androgen production. This produces an excessive
amount of adrenal (epirenal) androgens. In boys this syndrome is manifested
by premature puberty (adrenal form of precocious puberty), in girls - signs of
virilization, with the development of so-called "female
pseudohermaphroditism".
According to the generally accepted classification, there are 3 main
forms of adrenogenital syndrome:
166
• virile form - masculinization of external genitalia, male-type hair,

underdevelopment of mammary glands;
• Solteric (hypotensive) form - has the most severe course. In this form,
a large amount of sodium is excreted with urine, dehydration, collapse
develops, and death often occurs with the picture of adrenal crisis;
• hypertensive form - rare; arterial hypertension may appear as early as
infancy.
THYROID DISORDERS
The thyroid gland can have diseases that differ in their origin and
nature: thyroiditis, struma (goiter), and tumors.
In addition, depending on the level of thyroid hormone production,
three forms of functional state of the thyroid gland are distinguished:
• Euthyroidism - when the level of thyroid hormones (triiodothyronine
and thyroxine) is normal;
• hyperthyroidism - the result of hyperproduction of thyroid hormones
(the extreme degree of hyperthyroidism - thyrotoxicosis);
• Hypothyroidism is a consequence of a deficiency of triiodothyronine
and thyroxine in the body (extreme hypothyroidism is found in
myxedema).
► TYREOIDITES◄
Thyroiditis - inflammatory lesion of the thyroid

gland.
According to classificationthere's acute, subacute

и
chronic thyroiditis.
ACUTE THYROIDITIS
Acute thyroiditis is an acute inflammation of the normal thyroid gland
or goiter-altered gland (strumitis).
167
Figure 37. Classification of acute thyroiditis.
The disease has various etiologies: viruses, bacteria, fungi, other non-
infectious causes, including trauma, hemorrhage, and exposure to radiation.
Thyroid gland is enlarged, swollen. When examining the patient:
pain, fever, feeling of pressure in the region
of the gland projection.
Vacuolization of follicular cell cytoplasm, basophilia of colloid,

signs of exudative inflammation (serous, purulent, hemorrhagic,
mixed).
• local and general spread of purulent inflammation (purulent
mediastinitis, phlegmon of soft tissues of the neck, sepsis, etc.);
• fistulas into the trachea, esophagus;
• hypothyroidism.
168
SUBACUTE THYROIDITIS (DE QUERVAIN'S THYROIDITIS)
Subacute de Quervain's thyroiditis (giant cell thyroiditis,

granulomatous thyroiditis) is one of the most frequent forms of
subacute thyroiditis, a non-purulent inflammation of the thyroid
gland that develops after a viral infection (influenza, measles,
mumps, etc.).
Occurs 5-6 weeks after a viral infection (influenza, measles, etc.),

damage to the parenchyma of the thyroid gland with the development of
granulomatous inflammation is detected. Autoimmune inflammation plays a
significant role in the pathogenesis. Women are more often affected.
The gland is asymmetrically enlarged, small nodules are seen.
Presence of interstitial lymphocytic infiltrates, with giant

multinucleated cells, granuloma formation. Necrosis of follicles
is observed in the parenchyma, sloughed epithelial cells,
lymphocytes and leukocytes are detected in their lumen.
Around the affected
the areas are overgrown with connective tissue.
• persistent hypothyroidism
CHRONIC THYROIDITIS
The most common forms of chronic thyroiditis include Hashimoto's
autoimmune thyroiditis and Riedel's fibrous thyroiditis.
AUTOIMMUNE HASHIMOTO'S THYROIDITIS
Hashimoto's autoimmune thyroiditis is a chronic inflammatory

thyroid disease of autoimmune genesis.
Etiopathogenesis
The pathogenesis of the disease is based on autoimmune inflammation.
There is a genetic predisposition. Women are more often affected.
169
The occurrence of the disease can be preceded by any influences that lead to
disruption of the integrity of the structure of the thyroid gland and
penetration of thyroid antigens into the bloodstream (various infectious
diseases, inflammatory processes, less often - trauma to the thyroid gland or
thyroid surgery). Factors that can provoke autoimmune thyroiditis can also
be environmental degradation, iodine deficiency or excess, ionizing
radiation, etc.
Thyroid gland yellowish gray color, в
Nodes of different sizes and density are detected
in it
Diffuse infiltration of the thyroid gland B-
lymphocytes with an admixture of plasmacytes, replacement of
follicular cells of the organ and formation of lymphoid follicles
with light centers of reproduction. At the same time, as a result
of death of part of the organ parenchyma there is a partial
replacement of it by connective tissue. Islets of small follicles,
strands of
Ashkinazi cells. Regeneration of epithelium and epidermoid
metaplasia are noted in follicles.
• persistent hypothyroidism
INVASIVE FIBROTIC THYROIDITIS RIDDEL'S THYROIDITIS
Riedel's fibrous thyroiditis is an inflammation of the thyroid

gland characterized by destruction of the thyroid gland with the
formation of fibrous tissue in it, thickening of the thyroid gland
and compression of surrounding organs.
Etiology
The etiology of the disease has not been fully elucidated. It is currently
believed that fibrous thyroiditis occurs after a viral infection. Women of
middle and older age groups are more often affected.
The lesion can be uni- or bilateral. The thyroid gland pale,
stony dense. The affected
areas or lobes of the thyroid gland resemble tumor-like masses
masses extremely dense
170
consistency, the surface of the gland is often slightly lumpy. On

section, the parenchyma o f the gland is yellowish-white or gray,
layered, with barely visible bluish
veins.
Aggressive growth of connective tissue causing laryngeal

stenosis. Follicles are squeezed, vessel walls are sharply
thickened, moderate lymphocytic infiltration is detected, among
the cells of which are found
Langhans giant cells.
• the development of persistent hypothyroidism;
• compression of surrounding organs and tissues, neurovascular
bundles;
• formation of a malignant thyroid tumor
► STRUMA (ZOB)◄
Struma (goiter) - pathologic enlargement of the thyroid gland

associated with diffuse or focal (nodular) hypertrophy and/or
hyperplasia of its parenchyma.
The following is a classification of thyroid goiter. The most clinically

important are diffuse toxic goiter (Graves' disease, Bazeda disease), nodular
toxic goiter (thyrotoxic adenoma, Plummer's disease), and endemic goiter.
171
Figure 38. Classification of goiter.
DIFFUSE TOXIC GOITER
Diffuse toxic goiter (Graves' disease, Bazed's disease,

thyrotoxicosis) is an autoimmune disease characterized by a
persistent pathological increase in the production of thyroid
hormones.
Etiopathogenesis
Currently, diffuse toxic goiter is considered as an autoimmune disease with
hereditary predisposition, which is transmitted in a multifactorial (polygenic)
way. Factors provoking the development of the disease: mental traumas,
172
infectious-inflammatory diseases, craniocerebral trauma, nasopharyngeal

diseases. The disease usually begins in the pre- and pubertal periods.
Clinical manifestations
The disease is characterized by a clinical triad: hyperthyroidism, goiter, and
exophthalmos (bulging eyes).
• cardiovascular manifestations: arrhythmia, tachycardia, extrasystole,
systolic arterial hypertension, increased pulse pressure, development
of CVD;
• Endocrine and metabolic disorders: weight loss, weight loss despite
increased appetite, heat intolerance, increased basal metabolism;
• dermatologic symptoms: increased sweating, onycholysis, erythema,
swelling of the legs;
• neurological manifestations: tremor, weakness, headache, proximal
myopathy (difficulty getting up from a chair or squatting),
restlessness, anxiety, insomnia;
• ophthalmologic manifestations: elevation of the upper eyelid, lower
eyelid drooping (gaping), incomplete eyelid closure (Grefe's
symptom), exophthalmos (due to periorbital edema and overgrowth of
periorbital tissues).
Thyroid gland enlarged 3-4 times, irregularly dense, yellowish-
gray on section
The follicles are irregularly shaped, the follicular cavities are of

different sizes, and the colloid contained in them liquefies. The
follicular epithelium becomes high, cylindrical, forms folds
protruding into the follicular lumen (so-called "Sanderson's
pillows"), and may desquamate. The stroma of the organ shows
clusters of lymphocytes and lymphoid follicles with light
centers.
Changes in other organs:
• heart - "thyrotoxic heart",
thyrotoxic cardiomyopathy: fatty dystrophy and focal
necrosis of cardiomyocytes, lymphocytic myocarditis;
• liver - "thyrotoxic liver" - fatty degeneration of
hepatocytes, hepatitis;
• Lymphoid organs - generalized hyperplasia
173
lymphoid tissue;
• CNS - dystrophy of intermediate and medulla oblongata
neurons, microcirculatory disorders, cerebral edema;
• osteoporosis.
NODULAR TOXIC GOITER - THYROTOXIC ADENOMA

(PLUMMER'S DISEASE)
The clinical picture is similar in many ways to Graves' disease

Characterized by the presence of one or more nodules in the
thyroid gland
Nodes have micro- or macrofollicular structure. They most often

consist of Ashkinazi cells and may have a papillary structure.
ENDEMIC GOITER
Endemic goiter develops slowly and can be either diffuse or nodular
overgrowth of glandular tissue. This process occurs under the influence of
many factors, among which low iodine content in the environment is of great
importance.
Classification
By microscopic structure there is a distinction colloid,
parenchymatous and mixed goiter.
• in endemic goiter, in addition to hypothyroidism, there is mental
retardation, cerebellar disorders and different types of deafness due to
malformations of the inner and middle ear. It is likely that these
changes are not caused by hypothyroidism itself, but develop in
parallel with thyroid disease and are associated with iodine deficiency;
• sporadic goiter - appears in adolescence or adulthood. It can have the
structure of both diffuse and nodular, colloid or parenchymatous
goiter. Often, overgrowth of thyroid tissue leads to compression of
surrounding tissues.
174
Figure 39. Classification and microscopic features of colloid and parenchymatous

goiter.
► HYPOTHYPOTHYREOSIS◄
Hypothyroidism is a condition caused by a long-term, persistent

deficiency of thyroid hormones, the extreme degree of which is
myxedema in adults and cretinism in children.
Etiopathogenesis, classification
Depending on the etiology, the following types of hypothyroidism are distinguished:

• Primary (thyrogenic); develops due to:
-hypo- or aplasia of the thyroid gland;
-a congenital disorder of thyroid hormone synthesis;
- thyroiditis;
-peculiarities of nutrition (iodine deficiency);
- medical actions (removing of the gland, radiation
therapy, medications)
• secondary (pituitary); develops due to
hypopituitarism;
175
• Tertiary (hypothalamic); develops due to impaired synthesis and

transport of hypothalamic thyroliberin;
• tissue (transport, peripheral); develops due to:
- Inactivation of circulating blood T3 and T4 or TTG by
autoantibodies, proteases in sepsis, pancreatitis, shock;
- low sensitivity of target cell receptors to hormones;
+ congenital/acquired
Children have stunted growth, mental and intellectual development, trophic
changes in the skin and internal organs. The appearance is characterized by a
wide flat nose bridge, chicken nose, thick lips, puffy face, enlarged tongue.
The skin is rough, has the appearance of fish scales, peeling in layers. The
bones of the skull are underdeveloped, the bodies of the lumbar vertebrae are
underdeveloped.
• metabolic-hypothermic syndrome: obesity, decreased body
temperature, chilliness, cold intolerance, hypercarotinemia causing
jaundice of the skin;
• myxedematous edema: periorbital edema, puffy face, large lips and
tongue with tooth impressions on the lateral edges, swollen
extremities, difficulty in nasal breathing (associated with swelling of
the nasal mucosa), hearing impairment (swelling of the auditory tube
and middle ear organs), hoarse voice (swelling and thickening of the
vocal cords), polyserositis;
• nervous system syndrome: drowsiness, lethargy, memory loss, muscle
pain, paresthesias, decreased tendon reflexes, polyneuropathy;
• syndrome of cardiovascular system damage: myxedematous heart
(bradycardia, circulatory insufficiency), hypotension, polyserositis;
• syndrome of digestive system damage: hepatomegaly, dyskinesia of
bile ducts, dyskinesia of the colon, tendency to constipation, decreased
appetite, atrophy of gastric mucosa, nausea, vomiting;
• Anemic syndrome: iron-deficiency or B12-deficiency anemia;
• hyperprolactinemic hypogonadism syndrome: ovarian dysfunction
(menorrhagia, oligomenorrhea or amenorrhea, infertility),
galactorrhea;
176
• ectodermal disorders syndrome: hair is dull, brittle, falls out on the

head, eyebrows, limbs, grows slowly. Dry skin. Fingernails are thin,
with longitudinal or transverse striation, delaminate.
Hyperkeratosis and dystrophic changes in the epidermis, the
dermis is edematous, mucin-like substances accumulate in it. In
skeletal muscles - dystrophic changes, necrosis, their
replacement by fatty tissue. В
heart - myocardial edema, vacuolar dystrophy and myxomatosis
of cardiomyocytes, thickening of vessel walls.
• hypothyroid (myxedematous) coma;
• heart failure;
• effusion into the serosal cavities;
• secondary pituitary adenoma.
► THYROID TUMORS GLAND◄
The thyroid parenchyma is composed of three major cell populations:

• A-cells are specialized elements of the follicular epithelium that
produce thyronines;
• B-cells are derivatives of A-cells of follicular epithelium, rich in
mitochondria with high activity of succinate dehydrogenase. They are
practically not found in the norm; presumably they secrete serotonin;
• C-cells are parafollicular cellular elements, most likely of
neuroectodermal origin, that secrete calcitonin.
177
Classification
Figure 40. Classification of the major thyroid tumors.
THYROID ADENOMA
It occurs more often in young women. It is asymptomatic, sometimes
accompanied by thyrotoxicosis (Plummer's disease), hypercalcitoninemia
and hypocalcemia (in C-cell tumors) or syndrome of compression and
displacement of neck organs.
The tumor is more often represented by a single clearly
delimited nodule of various sizes with soft-elastic consistency.
On section: pink or brownish tissue (in B-cell tumors)
color, with cysts and hemorrhages.
• A-cell adenoma: immature small follicles devoid of

colloid or containing a small amount of colloid and lined
with cubic epitheliocytes. The stroma is friable,
edematous.
• B-cell adenoma (oncocytoma, Gürtle-Ashkenazi cell
adenoma): built of follicular, trabecular or papillary
structures. Cells
tumors of various shapes, large with eosinophilic
178
with fine-grained or homogeneous cytoplasm. The stroma

is differently developed, contains lymphocytic infiltrate.
• C-cell adenoma: solid layers of large, slightly elongated
cells with light or optically empty cytoplasm surrounded
by scant stroma.
THYROID CANCER
Background diseases for thyroid cancer are adenoma (especially
embryonal), chronic thyroiditis and nodular adenomatous goiter. Epithelial
dysplasia serves as a precancerous tissue change.
Papillary cancer
The most frequent form, usually asymptomatic, is detected incidentally by
ultrasound for multinodular goiter or chronic autoimmune thyroiditis.
yellowish-whitish dense nodule, on fine-
grained without clear boundaries on the section.
The tumor parenchyma is represented by papillary structures

formed by atypical and polymorphic thyrocytes with
overlapping of cells and nuclei on each other, multinucleated
cells.
Specific morphological features: nuclear grooves of different
depths, chromatin brightening of nuclei and nuclei "orphan
Anna's eyes", intranuclear cytoplasmic inclusions.
Follicular cancer
The second most common malignant tumor of the thyroid gland. It is
clinically asymptomatic or with thyrotoxicosis. The course of follicular
cancer compared to papillary cancer is unfavorable. The tumor is prone to
rapid growth and hematogenous metastasis.
A rounded nodule of colloidal appearance, often with a well-
defined
the border, the presence hemorrhages и petrificates of
stony density of different sizes.
The tumor is represented by follicles varying in diameter and

shape, and constructed of large polymorphic cells with light-
colored optically empty cells
179
cytoplasm and a hyperchromatic or lucent nucleus.

Characterized the presence fibrous capsule
(often с
petrification) with signs of micro- and macroinvasion into it.
Medullary cancer (C-cell).

It is more common in women over 40 years of age and, as part of hereditary
polyendocrine neoplasia, in young adults and children. Prognosis varies and
is in direct correlation with the size of the primary tumor. Metastases can be
both regional lymphogenic and distant hematogenous.
Single or multinodular foci of grayish-yellow color of different
diameter. With poorly developed stroma, the nodule is soft,
flabby, sometimes elastic to the touch. In amyloidosis of the
stroma, the tumor is dense, often
cartilage-like consistency.
Alveolar, rosette-like or small solid structures of small round or

elongated cells with scanty dark cytoplasm. The formation of
pericyte-like structures is characteristic.
Amyloidosis is noted
stroma, detected by congo red or genecyan violet.
Undifferentiated (anaplastic) cancer

It constitutes 4-15% of all thyroid carcinomas. Its frequency is the same in
men and women. It often develops against the background of a long-standing
nodular goiter. It is characteristic of elderly persons. Rapidly grows and
sprouts into the surrounding organs, quickly gives distant metastases. The
duration of the course of the disease is about 1 year.
Infiltrate of several merging nodules, without clear boundaries.
Can have 3 variations in structure:

• clusters of large, pleomorphic cells that resemble
osteoclasts separated by
layers of connective tissue, containing dilated, congested
blood vessels;
• a variant that resembles a spindle cell sarcoma;
• variant with groups of cells similar to squamous
epithelium, sometimes with foci of keratinization.
180
PARATHYROID DISORDERS
GILES
The parathyroid glands may develop various processes, including
congenital malformations. They consist of hypoplasia and even aplasia of the
glands, as well as heterotopia with the location of their fragments in the
thyroid gland or anterior mediastinum. The formation of accessory glands is
possible.
Hyperplasia of the parathyroid glands develops with increased
production of glundulotropic hormone from the pituitary gland.
Microscopically, the hyperplasia resembles a hypernephroma.
► HYPERPARATHYROIDISM
Hyperparathyroidism is a disease caused by excessive production

of paratgormone due to hyperplasia of parathyroid glands or their
tumor lesions and is characterized by a marked disorder of
calcium and phosphorus metabolism.
As a result of excessive formation of parathormone in adenoma or

hyperplasia of the organ, primary hyperparathyroidism occurs with the
development of fibrous osteodystrophy with numerous cysts. Secondary
hyperparathyroidism occurs as a compensatory response to prolonged
hypocalcemia of non-endocrine origin, for example, in children with chronic
renal failure.
Clinical and morphological manifestations

In the bones of the spine, pelvis, skull, flat chest, and short limbs,
lacunar resorption prevails over bone formation. In these areas, there is
increased endosteal proliferation, osteoclasts proliferate, often giant, cysts
and hemorrhages are formed. These changes are accompanied by
hypercalcemia, reduction of calcium content in bones, deposition of lime
("lime metastases") in places of calcium excretion (kidneys, intestines,
lungs), development of fibrous cystic osteitis and osteoporosis.
Calcium deposition in the middle sheath of arteries leads to
arteriosclerosis with arterial hypertension (Menkenberg's disease).
Deposition of calcium salts in myocardium leads to myocardial infarctions.
In the kidneys, nephrocalcinosis causes the development of urolithiasis.
Skin damage is manifested by deposits of calcium salts with necroses
("shell skin"), calcinosis of the auricles.
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► HYPOPARATHYROIDISM◄
Hypoparathyroidism is a disease caused by insufficient

production of parathormone
and accompanied by hypocalcemia.
Hypoparathyroidism develops with hypo-, aplasia or agenesis of the

perithyroid glands, autoimmune diseases, immunologic
deficiency, trauma, accidental removal during thyroid surgery, radioactive
iodine treatment, tuberculous lesions, or tumors with destruction of the
thyroid glands.
Clinical and morphological manifestations

There is a decrease in the reabsorption of calcium by the kidney
tubules and in the intestine, resulting in hypocalcemia and convulsive
syndrome in the form of tetany, frequent liquid stools, impaired development
of tissues of ectodermal origin (teeth, skin, hair nails), bones become brittle,
teeth crumble, fall out.
DISEASES WITH LESIONS OF INSULAR APPARATUS OF

THE PANCREAS
► DIABETES DIABETES◄
Diabetes mellitus is a chronic disease caused by an absolute or

absolute or relative insulin
insufficiency, leading to disorders of all types of metabolism
(primarily carbohydrate metabolism - hyperglycemia), vascular
damage (angiopathies), nervous system (neuropathies) and
pathological changes in various organs and tissues.
CLASSIFICATION
• Type I diabetes mellitus ("juvenile", insulin-dependent) - t h e basis
is destruction of β-cells of the islets of Langerhans, leading to the
development of absolute lifelong insulin deficiency;
• Type II diabetes mellitus (insulin-independent) - the basis is a defect in
insulin secretion against the background of insulin resistance;
• other forms of diabetes:
182
- genetic defects (abnormalities) of insulin and/or its receptors;

- diseases of the exocrine part of the pancreas;
- Endocrine diseases (endocrinopathies): Icenko-Cushing's syndrome,
acromegaly, diffuse toxic goiter, pheochromocytoma, etc;
-drug-induced diabetes;
-diabetes induced by infections;
-genetic syndromes combined with diabetes mellitus;
• Gestational diabetes mellitus is a pathological condition characterized
by hyperglycemia occurring against the background of pregnancy.
ETHIOPATOGENESIS
Type I diabetes mellitus
Type I diabetes mellitus is an inherited autosomal recessive form of
diabetes (the disease has been linked to the HLA gene on the short arm of
chromosome 6). Insulin-dependent diabetes mellitus is subdivided into two
subtypes:
• Diabetes 1A - the occurrence is associated with a defect in antiviral
immunity and it is believed that viruses, having tropism to the tissues
of islets of Langerhans, are able to damage the β-cells of the insular
apparatus.
• Diabetes 1B is a variant of autoimmune disease. The presumed
mechanism is the appearance of special clones of lymphocytes that
destroy cells of the insular apparatus.
The pathogenesis is based on absolute insulin deficiency in the body,
which leads to hyperglycemia and glucosuria. As a result, the osmotic
pressure in the urine increases and water reabsorption is impaired. Polyuria,
dehydration, thirst and polydipsia develop. With insulin deficiency, fat
formation decreases and fat breakdown increases. Patients quickly develop
weight loss, the formation of a large number of ketone bodies in the blood,
toxic to the brain. This form of diabetes is characterized by the rapid
development of clinical symptoms. Signs of decompensation (diabetic coma)
can occur within a few months and sometimes days from the onset of the
disease.
Type II diabetes mellitus

This form of diabetes is characterized by an autosomal recessive or
autosomal dominant type of inheritance (nucleotide alternation disorder has
been found in the
183
sequence of the short arm of chromosome 11). Structurally altered insulin

with impaired biological action appears. In this form of the disease, the
amount of insulin in the blood is normal or even increased.
The main prerequisite is obesity, which is associated with excessive
intake of carbohydrates into the body, increased need for insulin production,
increased load on β-cells, which ends in exhaustion of the insular apparatus.
Type II diabetes contributes to obesity as carbohydrate digestion occurs and
fatty acid breakdown decreases. The symptoms of this form of diabetes
develop gradually, usually without signs of decompensation.
In type I diabetes mellitus, infiltration of the islets of Langerhans with
lymphocytes, histiocytes, eosinophilic leukocytes, and death of β-cells are
noted. In the initial stages of the disease their regeneration is observed, and
later fibrosis and hyalinosis of islets develop.
In type II diabetes mellitus, the changes are less pronounced,
predominantly marked by a decrease in the number of β-cells.
Specific morphologic manifestations in diabetes mellitus:

• liver - steatosis, hepatocyte nuclei become bubble-like and contain
glycogen;
• large vessels - early development of atherosclerotic changes (diabetic
macroangiopathy), which often lead to the development of gangrene
of the lower limbs and intestines, as well as myocardial infarction;
• small vessels - diabetic microangiopathy, which is characterized by
plasmatic impregnation of basal membranes, leading to their
thickening, narrowing of vessel lumen, due to deposition of lipogialin,
sclerosis and hyalinosis of the vascular wall, sometimes with the
development of vasculitis;
• kidneys - diabetic nephropathy - focal or diffuse glomerulosclerosis,
tubular nephrosis, nephrosclerosis. In the epithelium of the narrow
segment of the nephron there is an accumulation of glycogen -
glycogen infiltration of the epithelium;
• retina - diabetic retinopathy manifested by damage to small retinal
vessels with microaneurysms, hemorrhages, extensive retinal
detachment and blindness;
• Peripheral nervous system - diabetic polyneuropathy - segmental
demyelination, edema and
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Axial cylinder dystrophy leading to impaired conduction and loss of

sensation of peripheral nerves, most often in the form of bilateral
peripheral neuropathy of the "glove and stocking" type, beginning in
the lower extremities. It is characterized by loss of pain, contact,
vibration and temperature sensitivity, which contributes to the
development of neuropathic ulcers and joint dislocations.
• defects in the phagocytic system (with the development of infectious
complications) - often joined purulent complications (pyoderma,
furunculosis, bronchopneumonia, sepsis), increases the risk of
pyelonephritis, tuberculosis, etc.
Fatalities occur from complications of the disease:
• myocardial infarction;
• cerebral circulatory disorders;
• gangrene of the lower extremities;
• renal failure;
• secondary infection;
• Hyperglycemic coma (2-5% of cases).
► TUMORS OF THE ENDOCRINE PART OF THE PANCREAS

GILES◄
Tumors of the endocrine part of the pancreas are hormonally active

and belong to the APUD system tumors.
• β-cell adenoma (insulinoma) macroscopically is usually small in size,
sometimes multiple nodules are found; clinical and morphological
manifestations are characterized by hypoglycemia and its sequelae;
• Gastrinoma (Zollinger-Ellison syndrome) - a tumor of small size is
characterized by excessive secretion of gastrin and hydrochloric acid,
G-cells of the islets of Langerhans. The disease is accompanied by the
development of peptic ulcers of the stomach and 12-intestine. Werner-
Morisson syndrome (water diarrhea) may develop;
• glucagonoma - adenoma with glucagon formation from proteins,
leads to a decrease in the level of amino acids in serum. Amino acid
deficiency leads to the development of necrotizing erythema
characterized by flaky, annular, irregularly shaped erythematous spots
and papules,
185
combined with dystrophic nail changes and glossitis;

• Somatostatinoma is a malignant pancreatic tumor with slow growth,
presenting with steatorrhea, impaired glucose tolerance and
hypochlorhydria.
CARCINOID SYNDROME
The epithelium of the digestive tract, respiratory and urinary tracts,
and the incretory part of the pancreas includes differons of scattered
neuroendocrine cells that form a diffuse endocrine system. They secrete
neuramins and protein (oligopeptide) hormones, which are products of amine
decarboxylation (Amine Precusore Uptake and Decarboxylation - APUD).
Tumorigenic transformation of such differons leads to the appearance
of trabecular or solid complexes, superficially similar to low-differentiated
cancer and named carcinoids.
Carcinoid tumors localizing to the pancreas can arise from A-cells, B-
cells, and G-cells and occur between the ages of 50-60 years. Malignant
tumors exhibit cellular polymorphism. Carcinoid tumors of the
gastrointestinal tract from enterochromaffin cells are most commonly found
in the worm, ileum, or stomach.
These tumors are often multiple, grow slowly, and reach large
in size, they're potentially
are malignant, have invasive growth, and metastasize to lymph
nodes.
The tumor consists of cells containing argyrophilic granules.

Immunohistochemical examination reveals neurospecific
enolase in them.
The clinical picture is due to the secretion of biologically active

substances, primarily serotonin and histamine. It is manifested by increased
blood pressure, periodic hyperemia of the skin, diarrhea, periodic attacks of
intestinal obstruction.
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SECTION VIII.
DISEASES OF THE MAMMARY GLANDS, FEMALE AND
MALE GENITAL SYSTEM
MAMMARY GLAND DISEASE

Among the diseases of the mammary glands distinguish diseases of
inflammatory genesis (mastitis), as well as non-inflammatory genesis,
including benign and malignant tumors.
► MASTIT◄
Mastitis is an inflammation of the mammary gland.
Etiology
• The most frequent causative agent is staphylococcus aureus
and streptococci;
• entry gate - fissures of the breast nipple, dermatologic diseases of the
skin of the mammary gland;
• most often develops during breastfeeding;
Classification
A distinction is made between acute and chronic mastitis (see Figure 41):
Figure 41. Classification of mastitis.
Acute mastitis
Focal or diffuse sealing с edema и
hyperemia.
187
Depending on the form of acute mastitis. Leukocytic

Infiltration in the ducts and surrounding tissue (purulent
inflammation), abscesses.
Chronic mastitis
Focal or diffuse sealing с edema и
hyperemia on exacerbation
Focal or diffuse lymphoplasmacytic infiltration, fibrosis and

atrophy of breast tissue. In case of specific etiology of the
process, typical granulomas with the presence of cells may be
observed
Pirogov-Langhans granulomatous mastitis.
• fistula formation;
• breast scarring
NON-INFLAMMATORY BREAST DISEASES
► ECTASIA OF MILK DUCTS◄
Ectasia of the milk ducts - pathological dilation of the milk ducts,

the place of localization of which is the subareolar region.
Etiology
• age factor: most often manifests itself during menopause, a s well as
at the initial stage of entering menopause;
• Hormonal imbalance (more often hyperprolactinemia);
• deformation of the milky canal due to trauma;
• inflammatory processes of various genesis;
• tumor process.
Painful hyperemic subareolar
mass, often with fistula formation, usually develops in women
who have given birth many times; associated with thickening of
the m a m m a r y secretion. When involved in
process of several segments the lesion is compared to a "ball of
worms".
188
Dilation and thickening of the duct wall due to fibrosis and

lymphohistiocytic, plasmacytic and neutrophilic infiltration;
atrophy of the duct epithelium; squamous cell metaplasia of the
duct epithelium is possible; in the surrounding tissue -
cholesterol deposition with a
with granulomatous inflammation.
The outcome of the disease is fibrosis with the formation of retractions of the
skin of the breast and breast nipple, requiring differential diagnosis with
breast carcinoma.
► FAT NECROSIS OF THE MAMMARY GLAND◄

Fat necrosis of the mammary gland - focal aseptic necrosis of
the fatty tissue of the mammary gland with its subsequent
replacement by scar tissue.
Etiology
• more often has a post-traumatic genesis, due to accidental bruises,
household injuries, medical manipulations;
• due to rapid weight loss weight or
radiation therapy radiation therapy;
• is occasionally seen in patients who have undergone mammoplasty
with their own tissue after mastectomy.
Dense, painful mass deforming the breast; skin retraction and
skin discoloration (grayish-white area of dense tissue with a
presence in the center of the
friable white mass with hemorrhagic component).
Around necrotic masses - macrophages loaded with fat

vacuoles, neutrophils; in chronic course - lipid crystals and
hemosiderin, around which is found granulomatous
inflammation with
by the appearance of giant foreign body resorption cells.
Outcome: scarring, cyst formation with organization.
189
► CYSTIC FIBROSIS CHANGES OF THE BREAST

(DYSHORMONAL)◄
Cystic fibrosis of the breast (dyshormonal) is a collective term

that includes hyperplastic and/or atrophic processes of the
parenchyma and stroma of the breast.
Cystic fibrosis mastopathy is one of the most frequent breast lesions.

Its incidence is 30-35%, and in combination with gynecologic diseases
increases to 52- 70%.; it has great clinical and radiologic similarities with
cancer.
In this disease there is a wide range of clinical and morphological
changes in the mammary glands, which is characterized by a combination of
small and medium-sized cysts, nodular formations (fibroadenomatosis,
fibroadenosis), stromal proliferation, hyperplasia and dysplasia of the
epithelium of the ducts and lobules of the glands.
Etiology
• genetic predisposition;
• Age over 40;
• endocrine disorders menstrual functions и other
endocrine organs;
• stressful situations, leading к
neuroendocrine dysregulation;
• aggravated obstetric and gynecologic history;
• Decrease in progesterone levels on the background of excessive
estrogen levels.
190
Classification and morphological manifestations
Epithelial hyperplasia (proliferative

form of mastitis)
Lobular hyperplasia Ductal hyperplasia

Epithelial proliferation 1. Simple ductal hyperplasia
1. Normal lobular hyperplasia 2.Atypical 2.Atypical ductal
lobular hyperplasia (neoplasia) hyperplasia
Hyperplasia (dysplasia or
Adenosis: neoplasia):
1. Small glandular adenosis • Solid type of growth
2. Apocrine adenosis 3.Sclerosing • Cribrosis type of growth
adenosis (Samba center) • Papillary growth type
191
BENIGN BREAST TUMORS
► FIBROADENOMA OF THE BREAST GLAND◄
A mammary fibroadenoma is a benign organ-specific tumor of

the breast that includes epithelial and fibrous components.
• is most common in women 25-35 years old;
• usually increases in pregnancy (the tumor has receptors for
progesterone), regresses with age;
• Malignization of fibroadenoma occurs rarely - in 0.1% of patients; in
the vast majority of cases carcinoma in situ is detected.
Dense, mobile, painless, well delimited nodule of white color
(usually not more than 3 cm in diameter) with slit-like cavities
on the section. Sometimes
can reach a large size (giant fibroadenoma).
It consists of glandular structures (ducts) of various shapes and

sizes. Epithelium lies on the basal membrane, retains polarity,
complexity. The stroma is represented by a large amount of
connective tissue (often loose and cellular), which
predominates over the parenchyma.
Two variants of breast fibroadenoma are distinguished:
• Intracanalicular adenoma: proliferating stroma grows
into the ducts, compressing them and giving them a slit-
like, bizarre shape resembling "deer antlers";
• pericanalicular fibroadenoma: fibrous stroma grows
around the ducts, making them look like rounded small
tubes.
Often both variants are found in the same tumor.
A separate type of fibroadenoma is a phylloid (leaf-shaped) tumor.

Nodes with diameters from 2-3 to 10-20 cm; on the section -
lobular structure with slit-like and cystic cavities, characteristic
network-like pattern resembling
sheet structure
192
Cell-rich stroma with glandular structures and signs of atypism.

The stromal component is often malignant with the
development of sarcoma (fibrosarcoma, fibrous histiocytoma,
less often liposarcoma). Benign, borderline and malignant are
distinguished
phylloid tumor variants.
► INTRADUCTAL PAPILLOMA OF THE BREAST

GILES◄
Intraductal papilloma of the breast is a benign tumor from the

epithelium of the mammary ducts, which is an outgrowth of the
wall of the excretory duct filling its lumen.
• evolves fromepithelium large or small of the

mammary ducts;
• more often solitary, risk of malignization is low.
Size 1-3 cm, the ducts are dilated with polypoidal

by the masses.
Fibrous papillae consisting of a fibrovascular pedicle lined by

bilayered epithelium.
MALIGNANT BREAST TUMORS
► BREAST CANCER GLAND◄
Cancer breast gland is represents the

most most common malignant tumor in women.
Etiologic risk factors

• A long reproductive life span;
• first births over the age of 30;
• obesity;
• treatment with estrogens, use oral
contraceptives;
• Cystic fibrosis in the breast with atypical epithelial hyperplasia;
• cancer in the contralateral breast and endometrium;
193
• hereditary predisposition.
Classification
Macroscopic classification of breast cancer
Histologic classification of breast cancer This classification is based

on two main features (see table):
• the presence or absence of invasion into the stroma;
• the source of the tumor (ductal or lobular cancer).
Non-invasive cancer Invasive cancer
1. A) Intraductal 1. A) Ductal
Б) Intraductal cancer B) Ductal cancer with Paget's
with Paget's disease disease
2. Intralobular 2. Slice
3. Medullary
4. Colloidal
5. tubular
Non-invasive lobular/ductal cancer (carcinoma in situ)

It has no characteristic macroscopic changes, it is discovered by
chance
Non-invasive lobular cancer - alveoli and terminal ducts are

dilated, contain monomorphic rounded cells with weakly
expressed signs of atypism.
194
Non-invasive ductal cancer - characterized by an overgrowth of

atypical epithelium in the ductal lumen with the presence of
mitotic figures, but without basal sprouting.
membranes.
Common features of invasive breast cancers

• Infiltrative carcinoma is able to grow inside the breast in all directions;
• Growth in the direction of the thorax leads to tumor ingrowth into the
deep fascia of the thorax and tumor fixation, retraction on the skin of
the breast;
• Involvement in invasive and metastatic processes of lymphatic vessels
draining the affected organ leads to lymphedema and thickening of the
skin with the development of the "orange peel" symptom;
• As the large ducts become involved, nipple retraction occurs;
• Involvement of most lymphatic vessels leads to swelling, hyperemia,
and soreness of the breast (i.e., "inflammatory" carcinoma);
• Metastasize lymphogenously (more often axillary area) and
hematogenously (lung, liver, bone, adrenal glands, CNS).
INVASIVE DUCTAL CANCER

Most common form. Most varieties of ductal cancer are made up of skirr
(skirrhotic, fibrous cancer).
Nodes cartilaginous of density, relatively well
demarcated from surrounding tissue
Atypical cells of ductal epithelium with hyperchromia of

nuclei, located in small nests, clusters, small tubes, infiltrating
fibrous stroma. According to the level of nuclear atypia and
general histologic differentiation of the parenchyma, the
following are distinguished
high, moderate, and low-differentiated forms.
INVASIVE LOBULAR CANCER

Has multicentric growth; bilateral lesions are often seen. The incidence
among all breast cancers ranges from 1 to 20%.
195
Node of dense-elastic consistency with indistinct borders
Expressed fibrous stroma, in which monomorphic cells with

optically empty cytoplasm are located, ring-shaped cells occur,
mitotic activity is low, the cells form "target-like" cells
structures. Difficult to distinguish from ductal. Mixed or
intermediate forms occur.
Due to the growth of breast cancer disease, not only diagnostic

criteria, but also prognostic criteria for various tumor variants have been
developed with the help of modern immunohistochemical research, allowing
to determine the proliferative activity and oncogenic potential of breast
cancer in order to prescribe adequate pathogenetic hormonal therapy.
According to IHC protocols, all operated patients are reactive to
estrogen and progesterone receptors and c-erb B-2 oncoprotein expression
(HER-2/neu) for administration of targeted therapy with antitumor
monoclonal antibodies (trastuzumab) (see Table).
Immunohistochemical markers for breast cancer diagnosis, prognosis and

targeted therapy
Diagnostic Predictive and
therapeutic
1. Cytokeratins are low 1. Estrogen receptors
molecular weights -7, 8, 18, 19. 2. Progesterone receptors
2. Epithelial membrane antigen 3. HER 2 /neu
(EMA), cancer embryonic antigen 4. Ki - 67 antigen
(CEA) 5. P 53
3. Collagen IV, vimentin,
smooth muscle actin
4. E- Cadherin
5. S is 100 protein
6. Chromogranin A
196
PAGET'S DISEASE (NIPPLE CANCER).
Paget's disease is a superficial cancer of the nipple and areola of

the breast.
• predominantly non-invasive carcinoma of the breastof the

breast (95%);
• A form of ductal cancer that originates in the lining of the milk
sinuses.
Nipple and areola lesions (cracks, eczema, ulceration)
The presence of Paget's cells in the epidermis of the nipple -

large cells with abundant light-colored or optically empty
cytoplasm and medium to large-sized nuclei; in the
the underlying tissue shows signs of ductal carcinoma.
CERVICAL DISEASE UTERUS
► CERVICITE◄
Cervicitis is an inflammation of the cervix.
Etiology
The primary cause is infectious agents (human papillomavirus, herpes virus,
chlamydia, gonococci, trichomonads, and pathogenic fungi). Associated risk
factors include:
• mechanical trauma resulting from manipulation (insertion, removal) of
the IUD, as a result of diagnostic procedures, abortions;
• birth trauma;
• weakened immune system;
• presence of other gynecologic diseases (vaginitis, vulvitis, etc.);
• prolonged intake antibacterial drugs,
glucocorticoid drugs, cytostatics;
• postmenopausal period.
Classification and morphological manifestations

197
It is customary distinguish two forms of this of this

pathology: exocervicitis и
endocervicitis.
According to the course, acute and chronic cervicitis are distinguished:
Acute cervicitis Leukocytic infiltration, edema and

hyperemia
Lymphohistiocytic
a
Chronic cervicitis
nd plasmacytic infiltration; epithelial
dystrophy, possible
its necrosis and desquamation with the
formation of a true erosion
The most common complications are:
• ascending infection (adnexitis, salpingitis), inflammatory processes in
the pelvis;
• bartholinitis;
• Cervical cancer (with HPV infection).
► PSEUDOEROSION (ENDOCERVICOSIS) OF THE CERVIX UTERUS◄
Pseudoerosion (endocervicosis) of the cervix is the replacement

of multilayer squamous epithelium (MPE) by cylindrical
epithelium to the outside of the transition zone between them (i.e.
in the vaginal part of the cervix) due to various pathological
processes.
If metaplasia of MPE into cylindrical epithelium develops without

preceding pathologic processes, such a phenomenon is called ectopia
(simple ectopia).
The source of ectopic cylindrical epithelium is considered to be
reserve cells located in the transitional (from multilayer squamous to
cylindrical) zone under the multilayer squamous and further under the
cylindrical epithelium. These cells are undifferentiated and, due to their
polypotency, can transform into both cylindrical and multilayer squamous
epithelium.
Classification
• Histologically:
198
-superficial variant (an area of the flat surface of the

ectocervix is covered with cylindrical epithelium);
-Glandular variant (formation of "erosive glands" lined
with cylindrical epithelium);
-papillary variant (formation of large papillary structures in the
focus of endocervicosis);
- glandular-papillary variant;
-Glandular-cystic variant (erosive glands are
transformed into retention cysts).
• By morphogenetic principle:
-Progressive (proliferative) endocervicosis;
-stationary (simple) endocervicosis;
-epidermizing (healing) endocervicosis.
Progressive endocervicosis (pseudoerosion)

The cervix is enlarged (edematous) due to inflammation and
fibrosis
Formation of glandular structures on the surface and in the

depth of the cervix. Growing in depth, the cylindrical
epithelium in the area of pseudoerosion forms glandular
passages resembling glands of the cervical mucosa. Glandular
structures are also formed at the expense of reserve cells
against the background of reserve-cell hyperplasia. In the
glands formed in the area of pseudoerosions, the epithelium
secretes a secretion.
During this period, pseudoerosion is referred to as glandular,
follicular, papillary, or mixed.
Stationary endocervicosis (pseudoerosion)

This is a phase of relative rest, when new glandular structures are not
formed, the pseudoerosion does not increase in size, but the healing process
has not yet begun.
In this stage, the pseudoerosion has a smooth surface without inflammatory
reactions, covered with cylindrical epithelium. The proliferation processes in
the cylindrical epithelium are stabilized.
Healing (epidermizing) endocervicosis (pseudoerosion)

199
It begins after the disappearance of inflammatory processes, elimination of hormonal

disorders and other pathological conditions.
The healing process is reversed compared to the progression of

pseudoerosion: on the one hand, the multilayer squamous
epithelium displaces the cylindrical epithelium formed from
reserve cells, and on the other hand, the regenerating MPE
grows up under the cylindrical one on the side of healthy
cervical areas.
The glands formed may overlap with the regenerating
epithelium from above, remaining deep in the cervix, and in the
absence of outflow from them cysts (ovula nabothi) are formed.
The processes of progression, stationary state and healing (epidermization)
may recur repeatedly, contributing to the aggravation of hyperplastic and
dystrophic changes. Parabasal and basal layers may be involved in the
process
epithelial cells с raising и distortion th
proliferative activities (basal cell hyperactivity, e
metaplasia, atypia). The appearance of atypia is considered a complication mof
basal cell hyperactivity and already corresponds to cervical dysplasia, an
obligate precancerous condition.
► CERVICAL CANCER UTERUS◄
Cervical cancer is a malignant neoplasm arising in the cervix,

presenting with two major histologic
varieties: adenocarcinoma and squamous cell
cancer.
Etiopathogenesis
Factors that increase the risk of cervical cancer:
• early onset of sexual activity (before the age of 16);
• frequent changes of sexual partners;
• smoking;
• infection with the human papillomavirus (HPV).
In most cases, the proven risk factor for cancer is human
papillomavirus serotypes 16 and 18.
200
Viruses of these serotypes are responsible for 65-75% of cervical cancer

cases.
The disease occurs against the background of previous precancerous
diseases: acute condylomas, chronic cervicitis, post-traumatic changes of the
cervix (ectropion after childbirth and rupture), pseudoerosions with impaired
differentiation of regenerating epithelium, leukoplakia (excessive
keratinization of multilayer squamous epithelium), CIN I-II.
The carcinogenic effect of HPV on cervical epithelial cells is to block
suppressor genes (genes that inhibit cell division), suppress apoptosis
(programmed cell death), activation of cell telomerase (an enzyme that
enables multiple cell division) by viral proteins.
NON-INVASIVE CERVICAL CANCER CERVICAL

INTRAEPITHELIAL NEOPLASIA
(CIN)
Microscopically, three degrees of CIN are distinguished:
• CIN I - changes are insignificantly expressed and are found only in 1/3
of the basal layer of the epithelium;
• CIN II - 2/3 of the epithelial layer is affected;
• CIN III - the entire thickness of the epithelial layer (carcinoma in situ).
Figure 42. Schematic representation of changes in CIN.
Appearance of cellular atypism and disruption of the

histoarchitectonics of the epithelium. Hyperchromicity and
pleomorphism of nuclei, abnormal distribution of chromatin
a n d increased nuclear-cytoplasmic ratio, koilocytosis.
Cellular atypism is accompanied by impaired epithelial
maturation and loss of polarity.
201
INVASIVE CERVICAL CANCER
Exophytic growth (mushroom or cauliflower shaped) and less

frequently endophytic growth (ulcerative-infiltrative). The
tumor is capable of sprouting into the bladder, ureters, and
r e c t u m . When sprouting
the ureters and rectum quickly become infected.
Histologic variants:
-squamous cell cancer;
- adenocarcinoma;
- glandular squamous cell;
- anaplastic;
- rarely - oat cell carcinoma (apudoma)
from the neuroendocrine cells of the endocervix.
Metastasizing
• Lymphogenic spread: from perineal and perineal lymph nodes, to
internal iliac and then para-aortic lymph nodes;
• hematogenous spread: the tumor gives dropouts to the lungs, and then
- to all organs in the great circle of blood circulation.
DISEASES OF THE UTERINE BODY AND ENDOMETRIUM
► INFLAMMATORY DISEASES. ENDOMETRITIS◄
Endometritis is a disease that is caused by an inflammatory

process in the superficial layer of the uterus - the endometrium.
Etiology
Inflammatory diseases of the female genital organs can occur under
the influence of mechanical, thermal, chemical factors.
The most significant is the infectious mechanism of lesions. The
causes of nonspecific inflammatory diseases can be various cocci, Candida
fungi, chlamydia, mycoplasmas, ureaplasmas, Escherichia coli, Klebsiella,
Proteus, Corynebacterium (Gardnerella), viruses, trichomonads and others.
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Classification
Depending on the type of pathogen, inflammatory diseases of the
female genital organs are divided into:
• non-specific;
• specific (gonorrhea, tuberculosis, diphtheria). By
the nature of the course of the disease:
• acute endometritis;
• chronic endometritis.
ACUTE PURULENT ENDOMETRITIS

It occurs as a result of abortion, childbirth, introduction of intrauterine
contraceptives, diagnostic uterine scraping and other intrauterine
interventions, especially those performed without taking into account the
degree of vaginal cleanliness or in violation of the rules of asepsis and
antisepsis.
Neutrophilic infiltration, especially in the gland lumen,

interstitial edema, hyperemia (fulminant hemorrhage), and
hemorrhage.
Complications: pyometra, sepsis, chronic endometritis.
CHRONIC ENDOMETRITIS
Risk factors for the development of chronic endometritis are all
invasive interventions in the uterine cavity, infectious and inflammatory
complications after childbirth and abortion, intrauterine devices (IUDs),
vaginal and cervical infections, bacterial vaginosis, cervical stenosis, uterine
cavity deformities, radiation therapy of the pelvic organs.
Lymphohistiocytic and plasmacytic infiltration is focal or

diffuse. Focal infiltrates have the appearance of "lymphoid
follicles" and are located in the basal and functional layer, they
also include leukocytes and histiocytes; focal fibrosis of the
stroma, sclerotic changes in the walls of spiral arteries
of the endometrium.
Complications: Dysplasia endometrial dysplasia, development
intrauterine
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fusions, i n f e r t i l i t y , spontaneous abortion, habitual miscarriages.
DYSHORMONAL DISEASES
From puberty to menopause, the endometrium undergoes cyclic
changes due to cyclic changes in pituitary and ovarian hormone levels.
Absolute or relative changes in the amount of estrogen and
progesterone are accompanied by impaired cyclic maturation and/or
rejection, atrophy or conversely hyperplasia of the endometrium.
The most common clinical manifestation of these disorders is
excessive bleeding during menstruation (menorrhagia) or outside
menstruation (metrorrhagia).
► DYSFUNCTIONAL UTERINE
BLEEDING◄
Dysfunctional uterine bleeding - uterine bleeding due to

impaired hormonal regulation of any genesis.
The major etiologic factors include:
• use of oral contraceptives;
• menopause;
• fibroids;
• polyps, hyperplasia and endometrial cancer;
• anovulatory cycle: lack of ovulation leads to excessive and prolonged
estrogen stimulation of the endometrium and absence of progestin
phase of the cycle.
Lack of secretory changes glands, the cystic
expansion. m
• corpus luteum insufficiency: causes low levels of progesterone, which
leads to incomplete secretory changes. It can be manifested by
bleeding, absence of menstruation (amenorrhea), infertility.
Endometrial scrapings produced during the progestin phase of the

menstrual cycle show a lag in secretory changes compared to those
expected on a given cycle day.
► HYPERPLASIA ENDOMETRIUM◄
Endometrial hyperplasia - diffuse changes in the uterine mucosa,

based on synchronous non-tumor proliferation of glandular and
stromal cells.
204
Hyperplasia of the endometrium is manifested by its thickening (normal

thickness of the basal layer is 1-1.5 cm; functional 1-8 mm, depending on the
phase of the cycle).
Etiology
• Increased and long-lasting estrogenic stimulation with decreased or
absent progesterone activity;
• occurs against the background of impaired secretion of gonadotropic
hormones of the pituitary gland and steroid hormones of the ovaries,
anovulatory menstrual cycle, sometimes with insufficiency of the
luteal phase;
• yellow body persistence, pregnancy, endometrial cancer, submucosal
leiomyoma or other submucosal neoplasms and pathologic processes.
Clinical and morphologic classification of endometrial hyperplasia
Figure 43. Classification of endometrial hyperplasia.
SIMPLE HYPERPLASIA WITHOUT ATYPIA

The main clinical manifestation is amenorrhea for 3-4 months, followed by
heavy bleeding.
The number of parenchymatous and stromal elements in the

entire thickness of the uterine mucosa increases. The division
of the functional layer into compact and spongiosal layer is
disturbed; glands have tubular structure, cysts are often formed.
The lining of glands and cysts is often single-layered,
corresponding to the proliferative phase of the cycle,
sometimes the epithelium may be pseudostratified, but it has no
signs of atypia. Sometimes squamous cellular
metaplasia.
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Cystic atrophy, rarely progresses to cancer.
COMPLEX HYPERPLASIA WITHOUT ATYPIA
Increased branching of glands, due to which the amount of

stroma decreases. Epithelium in the glands is pseudostratified,
forming true and false papillae. There are areas with numerous
irregularly shaped glands, the glands are located "back to
back". The epithelium is polymorphic, but retains a cylindrical
shape, sometimes there are areas of squamous cell metaplasia
and proliferation of "reserve" glands.
cells."
Development of endometrial adenocarcinoma (in 3% of cases).
ATYPICAL HYPERPLASIA
Distinctive features are cytologic atypia, which is manifested by
disruption of cell polarity in the glands, changes in the shape and intensity of
staining of the nuclei and structural changes in the tissue, manifested by the
predominance of glands over the stroma. Signs of atypia are usually focal.
In doubtful cases, in young women requiring differential diagnosis
with highly differentiated endometrial adenocarcinoma, it is recommended to
repeat uterine cavity scraping after 3-4 months. If under the influence of
progesterone therapy these changes disappear, the growth of cancer is
excluded.
The development of adenocarcinoma in simple atypical hyperplasia is
determined in 8% of cases, while in complex hyperplasia the development of
highly differentiated adenocarcinoma can be expected in 30% of patients.
► ENDOMETRIOSIS◄
Endometriosis is the presence of foci of endometrium outside the

uterus: ovaries, uterine ligaments, rectovaginal area, pelvic
peritoneum, scars, vagina, vulva, appendix, less often lungs and
liver.
206
The causes of the disease are not precisely established. Cellular

enzymes, hormone receptors, and gene mutations are thought to be involved
in the disease mechanism.
Classification
Figure 44. Classification of endometriosis.
The development of so-called "chocolate" cysts - cavity

formations, inside which there is a semi-liquid content of brown
c o l o r , the walls of the cyst are smooth, gray-brown. Such
changes are associated with
recurrent bleeding and hemosiderin deposition.
Presence of endometrial glands and stroma, fibrosis and

hemosiderin deposits.
Adenomyosis (internal e n d o m e t r i o s i s ) - characterized by the presence of

endometrial glands and stroma in the myometrium.
The uterine wall is thickened, granular on the section,
sometimes with small cysts and hemorrhages.
Foci of stroma and endometrial glands in the thickness of

myometrium, change depending on the menstrual cycle. Over
time, the foci of adenomyosis accumulate
hemosiderin.
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COMPLICATIONS,
• infertility; OUTCOMES
• posthemorrhagic anemia as a chronic
menstrual blood loss; consequenc
• e abdomen;
development of adhesions in the pelvis and
• the formation of endometrioid ovarian cysts;
• neurological disorders with compression of nerve trunks;
• malignization.
► BODY TUMORS UTERUS◄
A distinction is made between malignant and benign tumors of the

uterine body. Malignant tumors include epithelial, mesenchymal, mixed,
non-epithelial and secondary tumors.
ENDOMETRIAL POLYP
Endometrial polyp is a benign neoplasm formed as a result of

proliferation of cells of the basal layer of the endometrium.
The causes of endometrial polyps are most often disorders of

hormonal function of the ovaries due to increased content of female
hormones (estrogens) and insufficiency of gestagens (progesterone). The
formation of endometrial polyps can contribute to inflammatory processes of
the inner uterine lining, abortions, scraping of the uterine cavity.
The mass on the broad base has different sizes (0.5-3 cm)
и protrude в cavity of the uterus.
There are
single or multiple.
Microscopically, two histologic types of polyps are

distinguished:
• from the functioning endometrium, whose changes
develop in parallel with the phases and even stages of the
cycle;
• of hyperplastic endometrium with cystic enlargement of
the glands. This type of polyp can
coexist in parallel with the common
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dyshormonal endometrial hyperplasia.

There are fibrous polyps с cystic
dilated indifferent glands с
flattened epithelium- "senile"(occurs in
postmenopausal women).
COMPLICATIONS,
Polyps are OUTCOMES
precancerous disease и frequ
are malignant. ently
MALIGNANT EPITHELIAL TUMORS OF THE

ENDOMETRIUM (ENDOMETRIAL CANCER)
main cause of occurrence - prolonged estrogenic

stimulation leading to hyperplasia with subsequent malignization.
It can be polypoidal and diffuse with spreading throughout
throughout cavity organ с
lesion endometrium и
invasion of the myometrium.
Histologic forms:
• highly differentiated adenocarcinoma (G1) - good
visualization of glandular structures of the tumor
parenchyma;
• moderately differentiated adenocarcinoma (G2) - tumor
glandular component alternates with solid layers of
parenchyma;
• low-differentiated adenocarcinoma (G3) - predominance
of solid epithelial layers with marked nuclear atypia and
high mitotic activity.
There are rare forms of cancer: glandular squamous cell,
luminal cell (mesonephroic), papillary serous adenocarcinoma,
mucinous, undifferentiated.
Metastasis: primary metastases - to regional lymph nodes, then by

hematogenous route to lungs, liver, bones, etc.
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LEIOMIOMA
A leiomyoma is a benign tumor of smooth muscle.
Detected in 30% of women of reproductive age. Depending on
the localization are distinguished:

• intramural (located in the thickness of the myometrium);
• Subserosal (in the myometrium under the serous membrane);
• submucosal (under the mucosa);
• in the myometrium of the isthmic zone and cervix.
Clearly demarcated, round, dense, grayish-white on section,
fibrous masses; sizes ranging from small nodules to giant size,
filling the pelvis
cavity; diffuse forms occur.
Chaotically arranged bundles of smooth muscle cells

и connective tissue stroma, with the
predominance of the latter tumor is called fibroleiomyoma.
Bizarre forms of leiomyomas are characterized by cells of different

sizes and shapes with hyperchromic nuclei, multinucleated cells are found. It
is necessary to differentiate with leiomyosarcoma.
Secondary changes are possible: necrosis, hemorrhages, calcification,
hyalinosis, ossification.
OVARIAN DISEASE
The main types of ovarian pathology include non-tumor cysts, tumors,

and inflammation (oophoritis, adnexitis).
► NON-TUMOR OVARIAN CYSTS◄
FOLLICULAR CYSTS
Follicular cysts are formed from Graaf vesicles that do not undergo
rupture and ovulation.
Etiology
• changes occurring in the ovaries in inflammatory processes of the
appendages of the uterus - oophoritis, salpingitis, adnexitis;
210
• disorders of hormonal balance due to: uncontrolled use of hormonal

drugs, including contraceptives; childbirth; thyroid disorders;
hyperstimulation of ovulation during infertility treatment; stress, etc.;
• Follicular cysts can occur in newborn girls or during their intrauterine
development when: stimulation of the fetal ovaries with estrogens of
the mother; hormonal surge during labor.
A thin-walled cyst measuring 1-2 cm is filled with light serous
fluid и has smooth shiny
the inner surface is gray.
The cyst is lined with theca cells; an inner layer of granulosa

cells is found inconstantly; in old cysts it is
atrophied.
Partial or complete torsion cysts of the ovary; rupture
of a follicular ovarian cyst resulting in peritonitis.
CORPUS LUTEUM CYSTS

Etiology
The reasons for the formation of ovarian corpus luteum cysts are not completely clear.
• may be associated with hormonal imbalance and impaired blood and
lymphatic circulation in the ovarian tissues. The risk of luteal cyst
formation increases when taking medications to stimulate ovulation in
infertility or preparation for IVF and emergency contraception;
• does not exclude the possibility of formation of cysts of the yellow
body of the ovary under the influence of heavy physical and mental
stress, harmful working conditions, nutritional disorders, frequent
oophoritis and salpingo-ophoritis, abortions.
Usually single cavitary masses, with a yellow-colored lining.
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The cyst wall consists of luteinized granulosa cells and a layer

of theca.
Sometimes there is a rupture of the cyst of the corpus luteum with a
pronounced pain syndrome and bleeding into the abdominal cavity.
POLYCYSTIC OVARIES
It is characterized by the presence of cystic-expanded follicles and follicular cysts.
Etiology
• hormonal imbalance;
• infectious diseases;
• hereditary factor;
• stressful situations.
Usually is marker of Stein-Leventhal disease
Stein-Leventhal disease (oligomenorrhea and infertility,
anovulation, obesity, hirsutism).
The ovaries are enlarged, whitish gray, and have a smooth
outer part of the cortical substance. Subcortical
the zone contains a large number of cysts with sizes from 0.5 to
1.5 cm
Fibrosis of the superficial cortical layer under which follicular

cysts with hyperplasia of internal theca cells are found. Yellow
and white corpuscles are usually
are absent.
• complications of pregnancy in the threat of miscarriage, also possible
in the second half of hypertension and diabetes mellitus of pregnancy.
The risk of premature birth is slightly higher;
• malignant tumors of the uterus and ovaries. Increased risk is
associated with a prolonged disruption of the hormonal background.
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► OVARIAN TUMORS◄
• develop from the surface epithelium, germ cells, and stroma of the
ovaries;
• tumors from the superficial (coelomic) epithelium: serous, mucinous
and endometrioid;
• tumors vary in size, structure, and biological potency;
• suspicion of malignization is caused by the detection of papillae,
thickened lining of cysts, areas of solidification and necrosis.
The following is a brief description of the major and most common

benign and malignant ovarian tumors.
Serous tumor (serous cystoma)

A cyst with a fibrous wall that has a diameter of 10 to 40
cm
Histologic variants of serous cystoma:

• benign (cystadenoma) is characterized by a smooth,
shiny surface. The lining is represented by a high
cylindrical epithelium;
• border cystoma has papillary outgrowths in some places.
There is a more complex structure of papillae, in the
formation of which the stroma is involved, the
epithelium covering them has signs of stratification and
nuclear atypia. There are no signs of invasion into the
stroma;
• malignant serous cystoma
(cystadenocarcinoma) has papillary growths, nodular
and irregular thickening of the capsule. In addition to
cysts with papillary malignant structures, the following
are found
invasion of solid and cancerous complexes into the
ovarian stroma, psammoma cells.
Mucinous tumors
A large large number cysts of varying of
various sizes,
unilateral lesions. The total mass may reach 25 kg and contain
a viscous gelatinous fluid.
213
• Benign mucinous cysts are lined by high crescentless

cylindrical epithelium containing mucus in the apical
part of the cell (reminiscent of endocervical epithelium);
• borderline mucinous cystoma is characterized by more
intense growth of glandular (papillary) structures,
appearance of focal atypia of nuclei and stratification of
epithelium without invasion into the stroma of the ovary;
• mucinous cystadenocarcinoma has signs of cellular
atypism, stratification of the lining disappearance of
glandular structures, strata
solid structure, foci of necrosis.
Endometrioid tumors of the ovaries

Most tumors are represented by carcinomas. The benign variant is
cystadenofibroma with predominance of stromal component.
Macroscopically. tumor is represented combination
areas of solid structure and cysts, more often bilaterally with
brown foci
Highly differentiated forms predominate, more often

glandular squamous cell forms
Germ cell tumors of the ovaries

• germ cell tumors;
• are more common in children and young women;
• are represented more frequently by teratomas (95%): mature benign
teratomas and immature malignant teratoblastomas, monodermal and
highly specialized.
Mature benign ovarian teratomas

Most cases are cystic tumors. In practical work they are called dermoid cysts.
Single and bilateral unicameral cysts containing hair, serous
sebaceous material, dental tissues, foci of
calcification. The lining cyst is dull, leathery,
wrinkled, grayish-white.
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The cyst is lined with squamous epithelium, beneath which are

derivatives of the skin (sebaceous glands, hair follicles), other
structures of the germinal sheets (cartilage, bone, thyroid,
glandular
structures).
Immature malignant teratoma (teratoblastoma) Occurs less frequently than

mature teratoma; has rapid growth and often metastasizes.
The tumor is represented by a soft solid nodule with foci
necrosis and hemorrhages with the presence of sebaceous
material, hair, fragments of other tissues, calcifications
Areas of immature components differentiating into cartilage,

bone, glandular, muscular, nervous and
other fabrics.
Dysgerminoma
All dysgerminomas have a high malignant potential and aggressiveness.
Bilateral lesions, varying in size, juicy and fleshy, yellowish-
white on cut.
Stretch и complexes of the parenchyma consist

of large, rounded cells,
separated by a dense stroma с
lymphocytic infiltration.
TUMORS OF THE STROMA OF THE GENITAL TRACT
Granulosa cell tumors

• are rare and account for 2-5% of all ovarian tumors;
• consist of a granulosa cell component and a thecoma component;
• tumor cells produce estrogen. Depending on the age of the patient, the
hormonal activity of the tumor manifests itself differently: in children
(juvenile form) there is premature puberty, and in women of
childbearing age - meno- or metrorrhagia;
• can malignize at recurrence.
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The tumor is represented an encapsulated node.

On the section - solid and cystic, gray in color, in
the areas of
luteinization is yellow.
Varies microscopically depending on the combination of

components:
• The granulosa cell component is represented by cubic or
polygonal cells resembling normal granulosa cells. Cells
are arranged in the form of solid layers, strands, islets,
trabeculae;
• theca-cell component is represented by fields of theca-
tissue surrounding the granulosa islets, or cells of both
components are intermingled.
Tecomas and fibromas

• occur in 2% of patients. Predominantly observed in women
over 50 years of age;
• neoplasms developing from the ovarian stroma with
estrogenic activity. They are often mixed (tecofibromas)
Unilateral, rounded, sometimes lobulated, encapsulated, dense,
grayish-white, covered with shiny serous membrane of the
ovary. Characteristic
cystic cavities, areas of necrosis and hemorrhage.
• Fibromas consist of fibroblasts lying in a loose and

sparse stroma;
• thecomas consist of spindle-shaped cells with abundant
cytoplasm and lipid inclusions, surrounded by
argyrophilic fibers, with a large number of vessels.
Solid areas
are stained yellow due to lipid accumulation.
DISEASES OF THE MALE GENITAL SYSTEM
The most frequent diseases of the male genital system with the greatest
clinical significance are prostate diseases, in particular inflammatory
diseases (prostatitis) and prostate tumors.
216
► PROSTATITIS◄
Prostatitis - inflammation of the prostate gland, the most common

urologic disease among men of reproductive age.
Etiology
• Chronic prostatitis affects between 8% and 35% of men between the
ages of 20 and 40;
• Bacterial prostatitis (acute and chronic) in most cases is caused by
bacteria of the Enterobacteriaceae family, particularly Escherichia
coli (E. coli);
• The role of atypical microorganisms (chlamydia, ureaplasma,
mycoplasma) in the development of prostatitis cannot be considered
proven to date. In patients with human immunodeficiency virus (HIV),
yeast fungi (Candida spp.) and Mycobacterium tuberculosis may also
be etiologic agents.
The following types of prostatitis are distinguished:

• sharp:
- catarrhal - the inflammatory process is localized in the excretory
ducts of glandular lobules and has a non-purulent character.
Swelling of the mucous membrane of the ducts develops;
- follicular - there are multiple lesions of the lobules of the prostate
gland with the formation of a large number of small abscesses;
- parenchymatous-interstitial - diffuse lesion;
• chronic.
Acute prostatitis is characterized by purulent inflammation,
edema, fulmination, disseminated small abscesses, purulent-
necrotic foci. It is possible to develop
phlegmons
Chronic bacterial prostatitis is characterized by
lymphohistiocytic and plasmacytic infiltration with an
admixture of neutrophils and the development of sclerosis.
Recurrent urinary tract infections (urethritis, cystitis) are
significant.
Chronic microbial-free prostatitis is morphologically similar to
bacterial prostatitis
217
Prostatitis, but no history of recurrences

urinary tract infections.
► BENIGN PROSTATIC HYPERPLASIA◄
Benign prostatic hyperplasia is a benign mass that develops from

the glandular epithelium or stromal component of the prostate.
The prostate gland is a hormone-dependent organ under the control of
the hypothalamic-pituitary-gonadal system, and its growth, development,
and function are directly dependent on plasma testosterone levels.
Etiology
This pathology occurs in 95% of men over 70 years of age. The leading
significance is hyperestrogenemia due to metabolic conversion from
testosterone and androstenedione in men during physiologic or pathologic
male menopause.
Risk factors include: metabolic syndrome, diabetes mellitus, arterial
hypertension, diseases of the circulatory system.
The gland increases in size, is irregularly shaped, lumpy, soft-
elastic (in some cases dense-elastic). The enlarging middle lobe
leads to
to obstruction of urine outflow and consequent hypertrophy of
the bladder wall.
Morphological classification:
• glandular form;
• the muscular-fibrotic form;
• mixed form.
There is proliferation of gland end sections, their enlargement,
proliferation of fibrous-muscular stroma. Formation of
papillary formations and folds is possible. The end sections of
the glands are lined with bilayer epithelium. The inner layer
facing the g l a n d lumen is represented by cylindrical
exocrinocytes, and the outer, basal-oriented layer is represented
by cubic exocrinocytes
or flattened epithelium.
218
► PROSTATE CANCER GLAND◄
Prostate cancer is a malignant neoplasm arising from the

alveolar cell epithelium of the prostate gland.
Prostate cancer usually occurs in men older than 50-60 years of age. It is rare
in younger individuals.
Etiology
Genetic predisposition, progressive prostatic hyperplasia and the influence of
carcinogenic factors play a significant role in the etiology.
Cancer most often (90%) develops from the peripheral parts of the
prostate gland, while hyperplasia develops from the central and transitional
zone. A combination of cancer and prostatic hyperplasia has been reported in
5-25% of cases.
Classification
Histologic classification of prostate cancer:
• differentiated forms:
-adenocarcinoma (from glandular epithelium);
-Squamous cell cancer (from squamous epithelium);
- tubular cancer (from narrow channels lined with cubic or prismatic
epithelium, which may contain a secretion in the lumen);
- Alveolar cancer (from the end sections of branching glands);
• low-differentiated forms:
-anaplastic adenocarcinoma (characterized by changes in
intracellular structures, specific shape and size of cells);
-solid cancer (cells are arranged in layers or bundles separated
by layers of connective tissue);
-scirrhotic cancer (connective tissue stroma predominates over
tumor cells);
• undifferentiated forms:
- polymorphonuclear cell cancer (characterized by a large number of
dividing cells of different shapes and sizes);
According to morphological classification, prostate tumors are divided

into epithelial and
219
non-epithelial. In turn, epithelial tumors are divided into adenocarcinoma,

transitional cell carcinoma, and squamous cell carcinoma. The latter two
forms of cancer are extremely rare.
The main factors influencing the outcome of the disease are the
histologic structure of the malignancy, its stage, and prostate-specific antigen
(PSA) level.
In the morphologic diagnosis of prostate cancer, the most widely used
is the histologic Gleason classification, which is based on the degree of
differentiation of malignant cells.
Given the heterogeneity of most tumors, the Gleason score is
calculated by summing up the most common grades. According to the
Gleason classification, the degree of tumor differentiation is divided into 5
stages: from 1 - highly differentiated to 5 - low-differentiated, According to
the sum of stages, the Gleason score can vary from 2 to 10.
Adenocarcinoma with a grade of differentiation less than 6 has a low grade
of malignancy and a low-aggressive course.
G1: the tumor consists of
small homogeneous
glands with minimal
by changes in the nuclei;
glandular clusters, still
separated by stroma, but
nearer
to each other;
glands of various sizes
and structures and as a rule,
infiltrates the stroma and
surrounding tissue;
clearly atypical cells and
infiltrates
surrounding tissue;
G5: the tumor presents
layers
undifferentiated
of atypical cells.
Metastasis. Prostate cancer most often metastasizes to the bones, lymph

nodes, lungs, liver, and brain.
220
SECTION IX.
PREGNANCY PATHOLOGY. PATHOLOGY AFTERBIRTH
During pregnancy in the body of a woman significantly changes the

nervous and hormonal regulation of metabolism and physiological functions.
The development of the fetus is accompanied by the formation of complex
interrelationships between it and the maternal body. All these features can
act as a background, in which there are diseases associated with pregnancy.
Among them, the most important are ectopic pregnancy, trophoblastic
disease, as well as gestosis (toxicosis of pregnant women), including, among
others, pre-eclampsia and eclampsia.
► ECTOPIC PREGNANCY◄
An ectopic pregnancy is the implantation and development of a

fetal egg outside the uterine cavity.
ETHIOLOGY
В as risk factors risks development ectopic are:
• Abdominal surgery and adhesions;
• prolonged use of oral contraceptives;
• dyshormonal conditions;
• inflammatory diseases и infections female genital
organs;
• impaired transport function in the fallopian tubes;
• tumors of the uterus and its appendages;
• genital anomalies.
In a normal pregnancy, fertilization occurs in the tube and then the

zygote moves into the uterus where it implants. In an ectopic pregnancy, the
fertilized egg is unable to move into the uterine cavity and, more often than
not, implantation occurs in the tube. This is the most common variant of
ectopic pregnancy - 98% of cases. Such pregnancy is terminated, as a rule, at
4-6 weeks.
221
CLASSIFICATION
As of to date today there are two main
classifications of ectopic pregnancy:
1. By localization of the fetal egg:
• tubal pregnancy (the most common form);
• ovarian pregnancy;
• abdominal pregnancy;
• interligamentous pregnancy;
• cervical pregnancy;
• pregnancy in a rudimentary uterine horn;
• interstitial pregnancy.
2. By. stage onset и termination of an ectopic
pregnancy:
• advanced pregnancy;
• A terminated pregnancy like a tubal abortion or a ruptured tube;
• an aborted pregnancy.
In tubal pregnancy, decidual tissue, the fetal villous sheath, develops
in the fallopian tube mucosa. Chorionic villi penetrate the wall of the
fallopian tube, contributing to its rupture. The uterus in ectopic pregnancy
slightly increases in size, in the endometrium there are subtle decidual
changes.
An aborted tubal pregnancy occurs in two types:

• tubal abortion - complete or partial detachment of the embryo from
the wall of the fallopian tube and release of the ovum into the
abdominal cavity. The clinical picture of tubal abortion depends on
the intensity of bleeding (lower abdominal pain, presence of discharge
from the genital tract in the form of blood clots);
• a ruptured fallopian tube - usually occurs from 6 to
10 weeks gestation. It is characterized by the development of life-
threatening internal bleeding into the rectovaginal-uterine cavity
(Douglas pocket).
In other, rarer cases, the ovum exits through the ampullary section of
the tube into the abdominal cavity and there may either implant in the
follicular cavity of the ovary, with the development of a
222
ovarian pregnancy, or in the abdominal cavity with the development of

abdominal pregnancy.
The abdominal form of ectopic pregnancy:
• Primary abdominal pregnancy - when the egg implants on the
peritoneum primary;
• Secondary abdominal pregnancy - the fetal egg attaches to the
peritoneum secondary to a tubal miscarriage.
Implantation of the fetal egg in this form occurs in places free from
intestinal peristalsis (behind the uterus and even in the area of
parenchymatous organs such as the liver and spleen). Ends most often in
early fetal death with mummification or deposition of calcium salts in the
tissues ("paper fetus" or "stone fetus"). Very rarely, at late term, when the
placenta separates, massive hemorrhage begins and DIC develops.
In extremely rare cases, when a fertilized egg attaches to the mucosa
of the cervical canal, a cervical pregnancy may develop:
• a true cervical pregnancy;
• an isthmus-neck pregnancy.
When the fetal egg implants in the cervix or isthmus, the trophoblast
and then the chorionic villi rapidly sprout through the mucosa and penetrate
the muscular layers of the cervix to the parametrium, as the decidual reaction
of the mucosa is weakly expressed. Neck pregnancy is usually terminated in
the first half of pregnancy, which is accompanied by the appearance of
bloody discharge or persistent periodic bleeding. When the neck pregnancy
is terminated at a later stage, profuse bleeding develops, which cannot be
controlled.
For ectopic pregnancy (в in particular, for The
following complications are typical of tubal pregnancies:
- severe bleeding, which can lead to DIC and hemorrhagic shock;
adhesions; secondary
- infertility; infectious
- complications;
-
- repeated ectopic pregnancy at preservation
fallopian tube.
223
► TROPHOBLASTIC DISEASE◄
Gestational trophoblastic disease is a heterogeneous group of

tumor lesions associated with abnormal proliferation of placental
trophoblast.
Trophoblastic disease occurs with an incidence of 1:100,000 births,

predominantly in the 30-40 years of age.
CLASSIFICATION
According to the latest International Classification of Cancer
Diseases, trophoblastic neoplasms are distinguished among trophoblastic
neoplasms:
• bubble skid (full or partial);
• invasive bubblegum;
• chorionic carcinoma or chorionepithelioma;
• Chorionic carcinoma combined with teratoma or embryonal cancer;
• malignant trophoblastic teratoma;
• Trophoblastic tumor of the placental site.
By clinical course:
• benign;
• malignant (non-metastasizing, metastasizing: low risk, high risk).
By pathohistologic pattern:
• bubble burst;
• invasive skid;
• chorionic carcinoma.
FIGO International Classification (Singapore, 1992):
• Stage I - the lesion is limited to the uterus, there are no metastases;
• Stage II - there are metastases to the vagina or pelvis;
• Stage III - there are metastases to the lungs;
• Stage IV - other distant metastases are present.
Conditions such as vesicular skid and chorionic carcinoma are covered in detail below.
PUPPET BURNS
Bubble skid is a pathologically altered villous chorion with hydropic

transformation of the placenta.
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Multiple bubbles of varying size filled with clear fluid and

completely (complete carriage) or partially (partial carriage)
replacing the placental tissue. The elements of the vesicle may
be freely present in the
of the uterine cavity and be bound to the uterine wall.
Chorionic villi enlarged in volume due to sharply expressed

edema with formation in the central
some of these villi have cavities containing a mucus-like fluid.
There are 3 forms of bubblegum:

• complete bubble skid - is a consequence of fertilization of a defective
egg that does not contain chromosomes; in this case, further division
leads to the formation of a product of conception containing only
double the paternal genetic material. The embryo is not formed, but
only the growth of villi, followed by their transformation into bubble-
like formations. The tissues of the bubble skid at ultrasound are
detected in the form of a "snowstorm" effect;
• Partial bubble skid - formed when two sperm fertilize an egg
(69,XXY). Pregnancy may progress to term delivery of a viable fetus,
but more often fetal death occurs at 14-16 weeks or preterm labor with
fetal death in the antepartum or intrapartum period. The tissue of the
vesicle produces large amounts of chorionic gonadotropin and leads to
the formation of luteal cysts in the ovaries. In 3-5% of cases, the
vesicle transforms into a chorionepithelioma;
• invasive bubble skid - a form of trophoblastic disease, which is
accompanied by active proliferation of trophoblast with tumor
sprouting into the thickness of myometrium, sometimes up to the
perimetry with the development of severe intraperitoneal bleeding.
CHORIONIC CARCINOMA
Chorioncarcinoma (chorionepithelioma) is a malignant form of

trophoblastic disease arising from the chorionic epithelium after
bubble skid (up to 40% of cases), normal abortion (25%) and
childbirth (22.5%).
225
The key features of chorioncarcinoma are indicated below (Figure 45):
Figure 45. Key features of chorioncarcinoma.
Dark hemorrhagic mass of soft consistency with areas of

ulceration and decay.
Haphazard proliferation of trophoblast tissue, absence of

stroma, vessels and chorionic villi; presence of Langhans cells
and syncytial elements. The tumor consists of cytotrophoblast
(small round uninucleated cells with pale cytoplasm) and
syncytiotrophoblast (multinucleated cells) with different
degrees of atypia, nuclear pleomorphism, hyperchromatism and
with pronounced nuclei.
Metastasizes most commonly to the lungs, vagina, brain, liver, kidneys,

and intestines.
► HESTOSES◄
Hestosis is a complication of a normal pregnancy that can

manifest itself with edema, increased blood pressure, loss of
protein in the urine, and cramping.
According to ICD-10, gestosis is categorized as follows:

226
• pre-existing hypertension complicating pregnancy, labor and delivery

and the postpartum period;
• preexisting pre-existing hypertensionс with
proteinuria;
• pregnancy-induced edema and proteinuria without hypertension;
• induced pregnancy hypertension without significant
proteinuria;
• induced pregnancy hypertension with significant
proteinuria - moderate preeclampsia;
• eclampsia during pregnancy, in labor, and in the postpartum period.
According to the Russian classification there are 4 forms of gestosis, which

can be considered as consecutive stages of one process:
• hydrocele;
• Nephropathy (mild, moderate and severe);
• pre-eclampsia;
• eclampsia.
Among these gestoses, preeclampsia and eclampsia are the most important in
clinical practice.
ETHIOPATOGENESIS
Currently, there is no consensus on the etiology of gestosis, but there
are a number of theories, including cortico-visceral theory, endocrine theory,
immunologic theory, genetic theory, B and folic acid avitaminosis theory,
and placental theory.
The pathogenesis of gestosis is based on generalized vasospasm,
which is manifested by hypertension. Spasm occurs due to endothelial
damage. When damage occurs, endothelin is released into the blood, which
leads to vasospasm, including renal arteries and activation of the renin-
angiotensin system. Due to vasospasm, hypoxia, decreased anticoagulant
properties of blood, hypercoagulability and DIC develop. Microcirculation is
also disturbed, the permeability of the microcirculatory channel increases
and plasma output into the interstitium. Hypoxic (dystrophic) changes occur
in many organs: gestosis is accompanied by impaired function of the
kidneys, liver, nervous system, placenta.
227
PREECLAMPSY
Preeclampsia is a pregnancy pathology in which arterial

hypertension (pregnancy-induced) occurs
accompanied by with
significant proteinuria.
Preeclampsia is a syndrome characterized by the presence of

hypertension and proteinuria after 20 weeks of gestation, accompanied by
symptoms of multiorgan and multisystem failure: edema, visual
disturbances, headache, epigastric pain, etc.
Preeclampsia leads to the development of chronic placental
insufficiency and, as a consequence, delayed intrauterine development of the
fetus.
Maternal complications of preeclampsia are associated with
generalized vasospasm and include lesions of the brain (seizures,
hemorrhage), kidneys (oliguria and renal failure), lungs (pulmonary edema),
liver (edema, subcapsular hematoma), and microcirculatory vasculature
(thrombocytopenia, DIC).
ECLAMPSY
Eclampsia - one of the types of toxicosis of pregnancy, occurring

in the second half of pregnancy, in labor, as well as in the
postpartum period. Clinically, eclampsia is expressed by failure of
kidney and liver function, severe attacks of convulsions with loss
of consciousness.
The most characteristic feature of eclampsia is loss-of-consciousness

seizures not associated with any other cerebral pathology (e.g., epilepsy or
cerebral hemorrhage). Seizures in eclampsia are tonic-clonic and may or may
not be accompanied by an aura. Seizures may occur during pregnancy (25%
of cases), during labor (50% of cases), and in the postpartum period (25% of
cases). Most cases of postpartum eclampsia develop within the first 48 hours
after delivery, although cases of eclampsia several weeks after delivery have
been described.
228
Liver
Characteristic hemorrhages mainly under the capsule. Less
often there are light yellow areas of necrosis under the capsule.
The liver is mottled on the section - hemorrhages, foci
necrosis.
Accumulations of leukocytes, hyaline and coagulation thrombi

in small vessels, disruption of hepatic cell structure, moderate
fatty dystrophy and
necrosis, mainly along the periphery of the lobules with
deposition (later) of calcium salts.
The brain
The brain brain с small subarachnoid,
intracerebral hemorrhages и severe edema.
Thrombosis, perivascular foci of necrosis, with "ring"

hemorrhages, perivascular, pericellular and diffuse edema, and
dystrophic changes
nerve cells; later, fibrinoid necrosis of vessels (rare) and
proliferation of glia.
Kidneys
Cortical substance pierced large
infarct-like areas, limited by a red stripe ( hyperemia,
hemorrhages) from the cerebral
substances.
Swelling of the basal membranes of the tubular vessels and

dystrophic changes in the tubule epithelium. In rare cases of
eclampsia may occur total necrosis of the renal cortex,
combined with thrombosis of renal branch thrombosis
of the arteries.
Changes in other organs

• in the lungs, embolization with syncytium of villi, whole villi,
megakaryocytes, hepatic cells, as well as edema and hemorrhages are
often observed;
• blood is dark with a lot of clots, which indirectly proves its increased
coagulation;
229
• The spleen is enlarged; lymph nodes are large and bloody;

• in the mucous membrane of the stomach and intestine often observed
hemorrhages and erosions, on the serous cover - hemorrhages;
• The adrenal cortex is poor in lipoids, and the formation and
breakdown of basophilic cells are increased in the pituitary gland;
• dark red spongy areas in the placenta are often detected, round-shaped
seals, due to the increase in the volume of villi due to their sharp
hyperemia, with compression of the corresponding areas of the
intervillous space. The syncytium of closely located villi, which is not
washed by maternal blood, atrophies or, on the contrary, proliferates
with the formation of "syncytial kidneys".
COMPLICATIONS,
- pulmonary edema; OUTCOMES
- acute renal failure; cerebral coma;
- hemorrhaging in the adrenal glands and other vital organs;
- premature detachment of normally located placenta; placental
insufficiency, chronic hypoxia, antenatal fetal death.
-
-
In recent years, the frequency of complications associated with liver

dysfunction has increased. Thus, in gestosis, specific liver changes develop,
combined in the so-called HELLP-syndrome [H (hemolysis) - hemolysis;
EL (e1evvated liver enzymes) - increased level of liver enzymes; LP (1оw
р1аtelet соцпт) - thrombocytopenia]. In severe nephropathy and eclampsia,
HELLP syndrome develops in 4-12% of cases and is accompanied by high
maternal and perinatal mortality.
HELLP syndrome usually occurs in the third trimester of pregnancy,
more often at 35 weeks or more. The disease is characterized by a rapid
onset of symptoms.
Initial manifestations are nonspecific: nausea and vomiting (in 86% of
cases), pain in the epigastric region and, especially, in the right subcostal
region (in 86% of cases), marked edema (in 67% of cases), headache,
fatigue, malaise, hyperreflexia. Characteristic signs of the disease are
jaundice, vomiting with
230
blood, hemorrhages at injection sites, increasing hepatic failure, seizures and

coma.
Large patchy hemorrhages under the capsule are identified in the

liver.
Microscopically in the liver there are centrilobular necroses,

surrounded faint leukocytic infiltration,
plasma infiltration, signs of vasculitis.
► PATHOLOGY POSTDATE◄
In the normal course of labor 15 - 20 minutes after the birth of the

baby as a result of uterine contractions, the separation and expulsion of the
afterbirth from the uterine cavity occurs.
1. Age-related changes in the placenta

Age-related placental changes - occur at the end of pregnancy and are
particularly pronounced in overweight pregnancies.
2. Placental and umbilical cord malformations
• malformations of the weight and size of the
placenta:
- Placental hypoplasia - can lead to fetal hypoplasia;
- hyperplasia of the placenta - due to due to
angiomatosis,which is seen as a compensatory
process;
• placental malformations:
- a placenta surrounded by a placenta roll;
- a placenta surrounded by a rim;
- "terminal" placenta;
- bipartite placenta, etc.
• malformations of placenta localization (in relation to the internal
pharynx of the uterus):
- marginal placenta previa;
- central placenta previa;
• placental abruption malformations:
- placenta accreta - ingrowth of chorionic villi to a greater or lesser
depth in the endometrium and even in the myometrium. Placenta
accreta prevents the separation of the placenta after the birth of the
fetus, accompanied by uterine bleeding and requires surgical
intervention, up to the removal of the uterus;
- premature placental abruption - placental abruption that occurs
before the fetus is born. Its causes remain
231
unclear, it is more common in toxicosis of pregnancy. In

premature placental abruption, the fetus dies from intrauterine
hypoxia;
• umbilical cord malformations:
- A short umbilical cord - 40 cm or less. Such an umbilical cord
interferes with fetal movements and may contribute to transverse
positioning or breech presentation. During labor, the tension of a
short umbilical cord can lead to tearing or premature placental
abruption;
- A long umbilical cord - 70 cm or more. The presence of such an
umbilical cord can cause it to wrap around parts of the fetus, form
knots and fall out during labor.
3. Amnion malformations
- polyuria - an increase in the amount of amniotic fluid up to 2 liters
or more, often combined with fetopathies - hemolytic disease,
diabetic fetopathy;
- Low water - a decrease in the amount of water to 500 ml or less,
often combined with hypoplasia of the fetus and placenta and with
embryopathies;
- Amniotic fusions (Simonard's tendons) are dense connective tissue
hyalinized tendons or filaments running from the amnion to the
fetal surface. In fetuses, they cause furrows or amputation of limbs
or parts of limbs. They are particularly common in cases of low
water supply. The origin of the strands may be related to traumatic,
inflammatory or other injuries to the amnion.
4. Placental circulatory disorders: diffuse placental ischemia, diffuse
hyperemia, hemorrhage, edema, thrombosis, infarction, etc.
5. Inflammation
6. Placental insufficiency - the inability of the placenta to carry out basic
functions: transport, metabolic, endocrine, immune, hemodynamic, which
leads to death or pathology of the fetus or newborn.
• acute placental insufficiency - acute disorders of uteroplacental
circulation: premature placental detachment, extensive infarcts,
collapse of intervillous spaces, placenta previa;
• Chronic placental insufficiency - there is often a combination of
circulatory abnormalities (infarcts,
232
thrombosis of intervillous spaces, etc.) with various variants of villous

chorion dysembryogenesis.
Acute placental insufficiency more often leads to stillbirth, chronic - to
hypotrophy, immaturity, asphyxia premature and newborn.
233
SECTION X PRENATAL
PATHOLOGY
Prenatal (antenatal) pathology includes all pathologic processes

and conditions of the human embryo from the moment of
fertilization until birth.
The prenatal period in humans is 280 days or 40 weeks.
All development, from the maturation of the sex cell (gamete) to the birth of
the mature fetus, is divided into two periods:
• progenesis period - corresponds to the maturation of gametes (eggs and
sperm) before fertilization and is also called gametogenesis. During this
period, gamete abnormalities (gametopathies) may occur;
• kymatogenesis period - corresponds to the period from fertilization to
childbirth:
- blastogenesis - the period from fertilization to the 15th day of
pregnancy. During this period, the egg fragments and ends with the
formation of embryoblast and trophoblast (pathology -
blastopathies);
- Embryogenesis - the period from day 16 to day 75 of pregnancy, the
main organogenesis is underway and the amnion and chorion are
formed (pathology - embryopathies);
- fetogenesis - the period from day 76 to day 280 of pregnancy, the
differentiation and maturation of fetal tissues, the formation of the
placenta, and the birth of the fetus (pathology - fetopathies). In turn,
fetogenesis is divided into:
o Early fetal period (76-180 days of gestation);
o Late fetal period (181 -280 days of gestation).
ETHIOPATHOGENESIS
В in most cases etiopathogenesis of the development of
prenatal pathology is unclear. A number of factors are of definite importance:
• rubella, measles, herpes, hepatitis, mumps, polio, influenza and other
viruses;
• ionizing radiation;
• medicines (hormones and cytostatics);
• endocrine diseases maternal (diabetes mellitus
diabetes, thyroid disease);
• alcoholic и nicotine intoxication (alcohol
alcohol and nicotine intoxication (alcohol and nicotine
embryofetopathy), etc.
234
There are some patterns in the pathogenesis:

• damage to a particular organ or system is associated with the time of
action of etiologic factors on the fetus (teratogenic terminal period - a
period of time during kymatogenesis during which a teratogenic factor
is capable of causing the formation of an organ malformation);
• any pathogenic effect during morphogenesis leads to changes in the
formation of organs and systems;
• at late stages of development along with the violation of differentiation
in the organs and tissues of the fetus develop general pathological
processes - necrosis, hemorrhage, inflammation, hypo- and
hypertrophy.
► HAMETOPATHY◄
Gametopathies are injuries to the male and female gamete (egg or

sperm) that occur during ovo- or spermatogenesis prior to
fertilization.
The most important are defects in the genes of gametes (gene

mutations) and chromosomes (chromosomal mutations or chromosomal
aberrations), leading to the development of inherited diseases - gene and
chromosomal diseases, respectively.
GENE MUTATIONS
Genetic (gene) diseases are categorized into 4 types depending on the
type of inheritance:
• autosomal recessive (parents may be healthy and heterozygous carriers
of the defective allele); examples: accumulation diseases (Gaucher
disease, Niemann-Pick disease, etc.);
• autosomal dominant (parents also have the disease); examples:
familial hypercholesterolemia, Marfan syndrome, etc.
• recessive, X-linked (usually found in boys) - the mutant gene the child
receives from the mother, who is a carrier of the defective gene and
does not get the disease; examples: color blindness, hemophilia type A
and B, etc.
• dominant, X-linked; examples: hemophilia type C, Duchenne-Becker
muscular dystrophy, etc.
235
CHROMOSOMAL MUTATIONS
Chromosomal diseases are hereditary diseases caused by changes in the
number or structure of chromosomes. Chromosomal diseases include
pathological conditions caused by genomic mutations or structural changes in
individual chromosomes.
Typical examples of chromosomal diseases are Down's disease, Patau
syndrome, Klinefelter syndrome, Shereshevsky-Turner syndrome, and
Edwards syndrome. Below is a brief characterization of these syndromes.
Down's disease is a trisomy on 21 pairs of chromosomes (47) that is clinically
manifested by mental and physical r e t a r d a t i o n . The incidence of Down's
disease increases with the age of the mother.
The appearance of such a patient is characteristic:
• Brachycephaly (low forehead and slanted back of the head);
• slanted eyes;
• epicant (vertical fold skin semilunar (a
vertical semilunar skin fold covering the inner corner of the eye slit);
• the back of the nose;
• low, small ear flaps;
• muscle hypotonia;
• pathognomonic sign - spots Bruschwilde's spots
(areas of iris depigmentation);
• transverse palmar crease.
Usually, the cause of death in such cases is chronic heart failure on the
background of malformation of the cardiovascular system (more often septal
defects and tetrada Fallo) and leukemia.
Patau syndrome - trisomy on the 13th pair of chromosomes

(47). In addition to mental and physical retardation, these children have:
• low sloping forehead;
• cleft upper lip and hard palate;
• polydactyly and flexor hand position;
• Anophthalmia or microphthalmia and corneal opacity;
• microcephaly, arinencephaly;
• internal organ malformations.
• The pathognomonic sign is increased renal lobularity and polycysticism;
• ectopia of spleen tissue into the pancreas;
• uterine and vaginal doubling.
236
Klinefelter syndrome - karyotype 47 CW or CWC (CWC, CWC, CWC, etc.).

• is usually diagnosed after puberty;
• high stature due to long limbs;
• learning difficulties, rarely oligophrenia (25-30%);
• underdevelopment of the sex glands and infertility;
• gynecomastia;
• osteoporosis;
• obesity;
• type 2 diabetes.
Shereshevsky-Turner syndrome is a monosomy of 45 CHOs.

• stunting;
• infantile genital structure, amenorrhea, sterility;
• "barrel chest."
• short neck with "wing-like" folds;
• deformities of the auricles and elbow joints;
• These kids don't suffer intellectually, they live a long life.
Edwards syndrome - trisomy 18 pair (47).

• dolichocephaly with a stepped skull;
• microgyria (thinning, shortening and increase in the number of
gyrus of the large cerebral hemispheres);
• the flexor position of the hands;
• "rocking foot."
• syndactyly;
• cerebellar hypoplasia;
• The pathognomonic sign is thickening of the dorsal dentate nuclei of
the olive.
► BLASTOPATIQUES◄
Blastopathies - cymatopathies, arising в period

of blastogenesis (day 1-15 of antenatal development).
During blastogenesis, the zygote fragments and tissue embryos are

formed. The following most common variants of blastopathies are
distinguished:
237
• Blastula implantation pathology (ectopic pregnancy, superficial or deep

implantation of the blastula in the endometrium). Superficial
implantation more often leads to a violation of the location of the
placenta and spontaneous abortion, while deep implantation leads to
placenta accretion. A violation of implantation localization leads to
ectopic pregnancy, while deep implantation contributes to placenta
accretion;
• The formation of an empty germ sac due to aplasia or death of the
embryoblast;
• trophoblast aplasia/hypoplasia;
• Panembryonic anomalies (incompatible with life);
• malformations of individual organs, multiple or single (in half of cases
they are combined with malformations of provisor organs);
• twin deformities (conjoined twins) - develop when there is a common
zone between two crush centers. If the twin consists of equally
developed components, it is called "diplopagus", if one of the twins is
smaller than the other, the twin is called "heteropagus", and the smaller
twin is called a parasite. To indicate the localization of fusion, the word
"pagus" is added to the anatomical formation of the fusion site (e.g.,
craniopagus - fusion in the head, thoracopagus - fusion in the thorax,
ischiopagus - fusion in the pelvis). Twin deformities are usually
combined with non-viability.
► EMBRIOPATHY◄
Embryopathies - cymatopathies, arising в period

of embryogenesis (16-75 days of intrauterine life).
During embryogenesis, disorders are associated with the development

of congenital malformations, which are understood as a persistent
morphological change of an organ, body part or the whole organism, beyond
the variations of the normal structure of a certain biological species, arising as
a result of disruption of morphogenesis.
In addition to anatomical structure disorders, it is possible to develop
disorders at the tissue level - malformations of transverse striated muscles,
connective tissue, skin, bones of cartilaginous genesis, and others.
Classification of congenital malformations is presented below (see Fig. 46).
238
Figure 46. Classification of congenital malformations.
The following is a brief characterization of the major malformations

by organ system.
CONGENITAL HEART DISEASE

Congenital heart and vascular malformations represent one of the most
common types of malformations, second in frequency only to
239
central nervous system malformations.

Congenital heart defects can occur either in the chambers of the heart or
in the great vessels. The most common malformations are classified on the
basis of:
• of cardiac lesion patterns;
• the presence of a message or shunt between the two halves;
• for malformations with blood discharge by the presence or absence of
cyanosis (conditional, not always applicable):
- Blue-type malformations (with right-to-left blood discharge, with
mixing of arterial and venous blood) - cyanosis is observed, which
occurs as a result of right-to-left blood discharge, due to which
unoxygenated venous blood, bypassing the lungs, enters the great
circle of blood circulation (central cyanosis);
- malformations of the "white" type (pale, with left-right discharge of
blood, without mixing of arterial and venous blood).
Congenital heart defects, predominantly of the "white type"
Botall's (arterial) duct malformation - blood

from the aorta enters the pulmonary artery
through the open arterial duct. In case of
pulmonary hypertension - vice versa (in this
case - it is a "blue" type defect).
Ventricular septal defect is a congenital heart

defect characterized by a defect between the
right and left ventricles of the heart.
Hemodynamic disorders are expressed in the
discharge of blood through the defect from left
to right.
In the presence of pulmonary hypertension,
blood flow will be reversed (a "blue" type
defect).
240
Atrial septal defect is a congenital heart defect

characterized by a defect between the right and
left atria of the heart. Blood drains from left to
right. In the presence of pulmonary
hypertension, the blood flow will be reversed
(blue type defect).
Common arterial trunk originating from both ventricles. Blue type

malformation. Often in in this malformation
children end up
are unsustainable.
Complete transposition of the aorta and pulmonary artery. Blood flow in the
large and small circulatory circles is completely disconnected, oxygenated
blood can only enter the large circulatory circle through septal defects or
unexpanded
Botall's duct. The children are not viable.
Stenosis and atresia of the pulmonary trunk or aorta. Viability and prognosis
depending on the degree of stenosis and the degree of impairment
of the circulation.
Congenital heart defects, predominantly of the "blue type"

Fallot's triad - atrial septal defect, pulmonary
artery stenosis, right ventricular hypertrophy.
Hemodynamics: due to increased pressure in the
right heart (as a result of pulmonary artery
stenosis), blood flows through the opening in
the atrial septum into the left atrium, bypassing
the lungs.
Tetrada Fallo - interventricular septal defect,

pulmonary artery orifice stenosis, right
ventricular hypertrophy and aortic
dextraposition. Hemodynamics: a significant
proportion of venous blood drains from the right
ventricle directly into the aorta, where it is
mixed with arterial blood.
Fallot's pentad - anomalies characteristic of Fallot's tetrad + atrial septal

defect. Hemodynamic abnormalities are the same. With a small stenosis of
the pulmonary artery, the pressure in the right
The ventricle is small and appears lower than in the left ventricle,
241
so blood flows from the left ventricle to the right ventricle ("white type")
vice).
Tricuspid valve atresia + atrial septal defect. The main anatomical feature of
this malformation is the lack of communication between the right atrium and
the right ventricle. Hemodynamics: venous blood from the right atrium
enters the left atrium and there mixes with arterial blood. In the left ventricle,
some of the blood goes to the aorta and some goes to the
right ventricle.
Atresia (absence) of the right ventricle. Hemodynamics: venous blood from

the right ventricle enters the left ventricle and mixes with arterial blood.
From the left ventricle blood goes to the aorta, from the aorta part of the
blood goes through the Botall duct into the pulmonary artery
and into the lungs.
CNS MALFORMATIONS
Occur most frequently, with viruses and medications playing the largest
role in their etiology.
• Anencephaly - absence of the anterior, middle, or posterior parts of the
brain. The medulla oblongata and spinal cord are preserved;
• akrania, the absence of cerebral skull bones, is often combined with
anencephaly;
• microcephaly is hypoplasia of the brain;
• Microgyria - a decrease in the size of the cerebral gyrus with an
increase in its number;
• porencephaly is a cyst formation in the brain;
• hydrocephalus - accumulation of liquor in the ventricles of the brain
(internal) or in the subarachnoid space (external). In both cases, the
brain atrophies as a result of compression and the size of the fetal head
increases;
• Cyclopia - the presence of one or two eyeballs in one eye socket.
Usually combined with malformation of the nose and olfactory brain;
• hernias of the brain and spinal cord: the presence of brain membranes
in the hernial sac - meningocele; the presence of brain membranes and
substance in the hernial sac - meningoencephalocele; the presence of
brain membranes, substance and ventricles in the hernial sac -
meningoencephalocystocele. Spinal cord hernias are often associated
with splitting of the dorsal portions of the vertebral arches (spina
bifida).
242
CONGENITAL MALFORMATIONS OF THE DIGESTIVE ORGANS

The pathogenesis of the malformations is related to the impaired
formation of the digestive tube from week 4 to week 8 of intrauterine
development.
Malformations occurring in the digestive tube are most often associated
with the absence of the lumen of the hollow organs. This phenomenon is
called atresia. If the lumen exists but is narrowed, it is called stenosis.
Stenoses and atresia are seen in the esophagus, duodenum, proximal small
intestine, distal small intestine, distal jejunum, and anus.
At the same time with the presence of stenosis and atresia, there are
complications or fistulas of dysontogenetic origin. Thus, esophageal atresia is
often combined with a tracheo-esophageal fistula. Such a defect manifests
itself immediately after birth during the first feeding - the child chokes,
coughs. Aspiration and aspiration pneumonia occur. Viability and prognosis
depends on the degree of violation of the normal anatomical structure.
Hirschprung's disease. Absence of neurons of the nerve intermuscular
plexus of the sigmoid and rectum in the presence of submucosal (Meisner's)
plexus leads to spasm of the intestine and coprostasis of the overlying parts.
As a result, intestinal obstruction develops.
Hypertrophic pylorostenosis is congenital hypertrophy of the pyloric
gastric musculature with narrowing of its lumen. The pyloric lumen is narrow
and long. Vomiting and, as a result of chloride loss, coma rapidly develops.
Surgical treatment leads to disappearance of the symptoms of the disease.
GENITOURINARY CONGENITAL MALFORMATIONS

These malformations are characterized by great diversity, high
frequency of occurrence (10% of people in the population have congenital
anomalies of the kidney and urinary tract) and occur during the period of 4-8
weeks of cymatogenesis. These include:
• Kidney agenesis - the absence of one or both kidneys;
• Renal hypoplasia - underdevelopment of one or both kidneys. If one
kidney is hypoplastic, the other kidney undergoes compensatory
hypertrophy;
• Renal dysplasia - hypoplasia with simultaneous presence of embryonic
tissue (primitive tubules, tubules, and cysts);
• Cystic kidneys - cysts in the kidneys are located in the cortical layer and
between them are islets of normal developed renal parenchyma. Unlike
acquired cysts (pyelonephritis,
243
urolithiasis) there is no evidence of inflammation in cystic kidneys of

congenital genesis;
• Kidney fusion (horseshoe kidney). The fusion can occur at the upper or
lower pole and is not clinically apparent. This malformation is
discovered by accident;
• doubling of the kidney. It can be unilateral or bilateral. The accessory
kidney is located near or attached to the main kidney. The accessory
kidneys have a separate ureter, which may flow into the pelvis of the
main kidney, or into its ureter or bladder. It may not manifest clinically;
• doubling of the ureters and pelvis. Usually combined with the previous
anomaly - doubling of the kidneys. It does not manifest itself clinically;
• agenesis, atresia and ureteral stenosis;
• megaloureter;
• atresia, urethral stenosis;
• exstrophy - ejection of the bladder as a result of aplasia of its anterior
wall, peritoneum and skin of the anterior abdominal wall. The bladder
mucosa is on the surface of the body in the area of the anterior
abdominal wall. This leads to early infection and fetal death.
CONGENITAL MALFORMATIONS OF THE RESPIRATORY SYSTEM

The most clinically significant respiratory (lung) malformations
include:
• aplasia and hypoplasia of the bronchi and lungs;
• lung cysts;
• congenital emphysema - is detected in the postnatal period, causes a
sharp displacement of the mediastinal organs;
If the malformations of the respiratory system are compatible with life,
they may provide a background for the development of lung disease later in
life.
CONGENITAL MALFORMATIONS OF THE BONE, JOINT AND

MUSCULAR SYSTEM
Systemic skeletal malformations

• Chondrodysplasia. It's accompanied shortening и thickening of
the limbs. The malformation is combined with pulmonary hypoplasia.
• Achondroplasia. Abnormalities affect only bones of cartilaginous
origin, with and in this case. bones connective
tissue
244
of origin are developing normally. Shortening of the limbs, no

developmental abnormalities of the facial skeleton.
• Osteogenesis imperfecta is a congenital fragility of the bones. It is
characterized by multiple, often congenital fractures.
Malformations of the muscular system

• Systemic hypoplasia of muscle tissue. Example, Oppenheim's
congenital myatonia (related to early fetopathies), in which there is
hypoplasia of the transverse striated muscles. In the first months of
life, children die of pneumonia, the development of which is
associated with hypoplasia of respiratory muscles, except for the
diaphragm.
• Isolated malformations of the muscular system. The most important
of these include congenital true and false diaphragmatic hernia. In
false hernias, there is no hernia sac, there is a defect in the diaphragm,
the volume of which varies, through which abdominal organs, more
often loops of intestines, can penetrate into the thoracic cavity.
• Congenital torticollis - characterized by shortening of the
sternoclavicular-papillary muscle due to its focal fibrosis, which
causes the child's head to tilt to the affected side.
FACIAL CONGENITAL MALFORMATIONS
The major congenital malformations are:

• cheiloschisis is a cleft upper lip;
• palatoschisis is a cleft hard palate;
• micrognathia - hypoplasia of the mandible;
• hypertelorism - a wide distance between the eyes.
These malformations often combined с with other
multiple malformations.
► FETOPATIQUES◄
Fetopathies - cymatopathies, that develop в

fetogenesis (76-280 days of prenatal
development).
245
According to the classification, there are early (76-180 days of prenatal

development) and late (181-280 days) fetopathies, as well as infectious and
non-infectious fetopathies.
Characteristic morphologic features of fetopathies:

• Early fetopathies, like embryopathies, are often accompanied by the
formation of organ malformations, late fetopathies are manifested by
tissue malformations;
• A combination of tissue differentiation disorders and reactive
changes (inflammation, immune response, regeneration) is typical
for fetopathies. Reactive changes in late fetopathies are more
pronounced;
• pronounced hemorrhagic manifestations (hemorrhagic syndrome)
are common;
• in the course of regeneration of damaged tissues develops
proliferation of mesenchyme;
• foci of extramedullary hematopoiesis persist in the postnatal period
longer than usual.
INFECTIOUS FETOPATHIES
Pathways of infection: hematogenous (transplacental), ascending
(through the vagina, cervix), descending (through the fallopian tubes).
Pathologoanatomical changes in tissues are associated with the type of
pathogen. The peculiarity of infectious fetopathies is a generalized, often
septic lesion.
In all infectious fetopathies there is a generalized, and in bacterial and
fungal - septic type of changes with formation:
• multiple foci of areactive necrosis in the parenchymatous organs and
brain (in congenital varicella, herpes simplex, cytomegaly, Coxsackie
virus infection);
• productive diffuse inflammatory infiltrates in combination with
areactive necrotic foci (congenital serum hepatitis, cytomegaly, rubella,
toxoplasmosis);
• granulomas in many organs (congenital syphilis, listeriosis,
tuberculosis, fungal lesions).
In this case, against the background of generalized lesions may prevail
changes in certain organs, for example, in toxoplasmosis - in the brain, in
serum hepatitis - in the liver, in infection with Coxsackie virus - in the
myocardium and brain, etc.
As a rule, there is a pronounced hemorrhagic syndrome in the form of
petechiae on the skin, mucous membranes and serous membranes,
246
hemorrhages in internal organs, the propensity for which in the infectious

process increases due to the development of generalized vasculitis.
Immune reactions of the fetus are expressed in the delayed maturation
of the thymus, in its atrophy with a decrease in its volume and weight, in the
presence of foci of extramedullary hematopoiesis in premature fetuses, and in
premature fetuses - in the increase in their volume, which is accompanied by
hepato- and splenomegaly.
Conjugation jaundice, tissue immaturity of organs in preterm or
prematurity and general fetal hypotrophy are common.
NON-INFECTIOUS FETOPATHIES
Among noninfectious fetopathies, diabetic, thyrotoxic and alcoholic
fetopathies, fetal hemolytic disease, endocardial fibroelastosis, and fetal cystic
fibrosis are of major importance.
Hemolytic disease of the newborn

See Perinatal Pathology.
Fetal cystic fibrosis is a disorder of the nature of mucus and other secretions
due to disruption of the structure of the mucoids they contain. Most often the
lesion affects the pancreas with atrophy of its parenchyma, closure of the ducts
of the gland with viscous secretion and cyst formation. In the pulmonary form,
obturator atelectasis develops in the lungs with the development of
inflammatory diseases in the lungs. When the intestine is affected -
phenomena of coprostasis, perforation and fecal peritonitis.
Endocardial fibroelastosis is characterized by the development of connective

tissue in the subendocardial part of the heart. Etiology: inflammation,
including autoimmune, metabolic disorders, in some cases there is a genetic
predisposition.
• dilated type of left ventricular endocardial fibroelastosis - globular
heart, left ventricular hypertrophy is noted;
• contractile endocardial fibroelastosis - decrease in the size of the left
ventricle with enlargement of the right ventricle.
Death may occur as a result of acute heart failure in the first days of life
or with increasing heart failure in the first months of life with intercurrent
illnesses.
247
Diabetic fetopathy is a fetal disease caused by maternal diabetes. It is

manifested by the birth of large fetuses weighing more than 4 kg. At the same
time, there are multiple signs of immaturity of various organs and tissues.
Diagnostic criteria:
• high birth weight and length (macrosomia);
• pastosity, hypertrichosis, purplish-blue coloration of the
skin;
• puffy, full-blooded face;
• clinical symptoms of hypoglycemia;
• SDR due to surfactant deficiency;
• cardiomegaly and congenital heart disease;
• Hepato- and splenomegaly;
• hypocalcemia, hypomagnesemia.
Fetal Alcohol Syndrome is a combination of congenital mental and physical

defects that first appear at birth and remain with the child for life. It is a
lifelong disorder that does not go away with age. This syndrome includes
abnormalities in three different areas:
• brain abnormalities and disorders related to the central nervous
system, including neurological abnormalities, mental retardation,
behavioral disorders, intellectual disabilities, and/or brain structure
abnormalities;
• Prenatal and/or postnatal height and weight deficits;
• specific features of the facial and cranial structure:
-short and narrow eye slit;
-wide, flat nose bridge;
-smooth lip groove;
-thin upper lip (upper lip border);
- microcephaly;
- epicanthus;
-hypoplasia of the upper or lower jaw;
-splitting the palate;
- micrognathia.
248
SECTION XI PERINATAL
PATHOLOGY
Perinatal pathology includes all pathologic processes and

conditions during the period from the 22nd full week (154th day)
of fetal life to the 7th day of the postnatal period inclusive.
Diseases occurring in the perinatal period are called perinatal

pathology. As a rule, manifestations of these diseases continue in older
children, especially in the late neonatal period (up to 28 days inclusive).
A newborn is a baby who has begun to breathe on his or her own. A stillborn
is a fetus that is not breathing at the time of birth and cannot be induced
artificially. The heartbeat of a stillborn fetus may continue for some time.
Stillbirths and deaths of children in the first 7 days after birth are
called perinatal deaths. The most common causes of perinatal mortality are
asphyxia, infections, congenital anomalies, and respiratory distress
syndrome.
The perinatal period consists of three periods:

• Antenatal or prenatal period - lasts from the 154th day of intrauterine
development until the onset of labor;
• The intrapartum period - takes up the entire period of labor;
• early neonatal (postnatal) period - after delivery for 7 days.
К basic forms perinatal pathology include

the following pathological processes:
• prematurity;
• prematurity;
• hypoxia (asphyxia) of the fetus and newborn;
• pneumopathy;
• birth trauma;
• perinatal cerebral circulatory disorders;
• hemorrhagic disease of the newborn;
• hemolytic disease of the fetus and newborn baby
+ infectious perinatal pathology.
The etiopathogenesis of perinatal pathology is diverse, but the most common

risk factors include:
249
-mother's age;
-social conditions;
-harmful working conditions of the mother;
-harmful habits (smoking, alcohol);
-concomitant extragenital pathology;
-number of previous births;
-fetal weight;
-fetal condition at birth;
-unprofessional medical staff, etc.
► PREMATURITY AND PREMATURITY◄
Timely delivery - в at term с 37

full week to the end of the 42nd week of
pregnancy.
Preterm labor - births occurring at 22 to 37 full weeks and with a
fetal weight of more than 500 grams.
Prematurity - birth before 37 full weeks of fetal development (less

than 259 days).
There are 4 degrees of prematurity:

Degree of Gestational age, Body weight, g
prematurity weeks
I 36-37 2001-2500
II 32-35 1501-2000
III 31-28 1001-1500
IV Less than 28 Less than 1000
Nowadays, the diagnosis usually does not specify the degree of prematurity,
but the gestational age in weeks (a more accurate indicator).
In the case of preterm l a b o r , the fetus born has a

signs of prematurity:
• lanugo (downy hair on the skin, in preterm newborns on the shoulders
and back, in premature newborns - on the face, thighs);
• The nails are thin and do not reach the end of the nail bed;
• failure of the testicles to descend into the scrotum (in girls - gaping of the genital
slit);
• the soft, pliable bones of the skull;
• wide sutures and large fontanels of the skull bones;
• absence of ossification nuclei in the epiphyses of tubular bones;
250
• body length less than 35 cm, weight less than 2500 g;

• skin wrinkled, dark red, covered with an
abundant cheesecloth-like lubricant;
• subcutaneous fat layer is not expressed;
• the umbilicus is located in the lower third of the abdomen.
In addition to external manifestations in prematurity, there are also changes in
the internal organs and systems:
• respiratory organs - surfactant insufficiency, so more often develop
pneumopathies in the form of atelectasis;
• Cardiovascular system - muscular hypotonia of transverse striated and
smooth muscles; high vascular permeability; more often develops and
more severe hemorrhagic disease, including cerebral hemorrhages;
• liver, spleen - foci of extramedullary hematopoiesis;
• blood - more nuclear forms of erythrocytes (normoblasts) and higher
content of fetal hemoglobin, as a result of which hemolysis develops
and hemolytic anemia is formed.
Prematurity is the birth of a baby at a gestational age of 42 full

weeks (294 days) or more.
The risk factors for carrying a pregnancy to term are:

• late puberty;
• menstrual dysfunction;
• infantilism;
• Previous childhood infectious diseases;
• metabolic disorders;
• endocrine disorders;
• inflammatory diseases of the genitals;
• psychic traumas;
• gestosis;
• disorders of the hypothalamic-pituitary-adrenal system of the fetus;
• indications of a history of overpregnancy.
Signs of prematurity:
• dry, flaky, macerated skin of yellow or yellow-green color as a result
of its impregnation with meconium amniotic fluid;
• narrow sutures and cranial fontanels;
251
• dense skull bones;

• low birth weight;
• nails protrude beyond the edge of the nail bed;
• signs of placenta aging - white infarcts, petrificates.
Prematurity and prematurity often lead to pathology and death in the

perinatal period. Infectious diseases, respiratory distress syndrome and
congenital malformations are the most frequent causes of death among
premature infants.
► INFECTIOUS PERINATAL PATHOLOGY◄
Infectious diseases of the fetus and newborn can be caused by a

variety of microorganisms, the most important of which are viruses (herpes
simplex, cytomegaly, hepatitis, rubella, HIV, respiratory and enteroviruses).
The fetus may also be affected by bacteria (pale treponema, listeria,
Mycobacterium tuberculosis), mycoplasmas, chlamydia, fungi and protozoa
(toxoplasma). Infection is most often acquired from the mother, primarily
antenatally, less often intrapartum.
Infectious diseases have a number of peculiarities compared to the
newborn period:
• delay maturation tissues в in combination с with or
without tissue dysplasia;
• special special character immune response с
massive extramedullary proliferation of myeloid sprout;
• excessive connective tissue formation.
Below summarized brief description the main The main

factors causing infectious diseases in the perinatal period are summarized
below:
Rubella
Intrauterine rubella in the first trimester of pregnancy leads to fetal infection
in 25% of cases and can lead to the development of congenital
malformations (rubeolar embryopathy). If the disease develops in the second
or third trimester of pregnancy, the risk of fetal disease is reduced to 3.5%
(rubeolar fetopathy).
• rubeolar embryopathy - characterized by the development of the
classic Gregg's triad: anomalies of the heart, organ development
252
hearing and vision. In addition, dental rudiments and the CNS

(microgyria) are often affected;
• rubeolar fetopathy - characterized by prematurity, encephalitis,
dermatitis, endophthalmos with retinal detachment, and interstitial
pneumonia in the lungs.
Cytomegaly
The causative agent of this disease is a DNA-containing human
cytomegalovirus from the herpesvirus family (Herpesviridae).
It can persist in the mother's body for a long time and can be
transmitted transplacentally or by the ascending route (vagina, cervix,
cervical canal).
Infection in early pregnancy results in the death of the embryo. If
infection occurs later in pregnancy, the fetus does not die, but hemorrhagic
diathesis develops and liver function is impaired. Jaundice has the character
of mechanical jaundice, and is caused by obturation of the bile ducts by the
virus. The prognosis of the disease is unfavorable. Surviving children
develop symptoms of CNS damage (microcephaly, hydrocephaly).
Syphilis
The causative agent is capable of penetrate through
placenta only in the second half of
pregnancy. There are three forms of the disease:
• syphilis of stillborn premature fetuses - the fetus dies intrauterine in
the 6th-7th month of pregnancy. F e t a l death is explained by the
direct toxic effect of the pathogen on fetal tissues. Such pregnancy
ends with premature delivery of a macerated fetus;
• early congenital syphilis - internal organs are affected - kidneys, lungs,
liver, skin. Specific inflammation develops in the tissues with the
formation of syphilitic gummas;
• late congenital syphilis - characterized by the Getchinson triad
(characteristic deformity of teeth, parenchymatous keratitis and
deafness). Organ lesions are characteristic of tertiary syphilis. In
addition to the Getchinson triad, chronic interstitial inflammation
develops in the tissues, in which the lungs, aorta, myocardium, and
liver are affected. A feature of late congenital syphilis in the lesion of
the thymus with the formation of abscesses Dubois - cavities
containing serous fluid with an admixture of leukocytes. These
cavities are bounded by a shaft of epithelioid cells. Late congenital
syphilis manifests itself several years after birth, sometimes as early as
high school age.
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► FETAL ASPHYXIA AND NEWBORN◄
Asphyxia - suffocation or acute oxygen deprivation with the

development of hypoxia and hypercapnia.
ETHIOPATOGENESIS
The following types and causes of asphyxia are distinguished:

• antenatal asphyxia - asphyxia occurring before delivery. It develops as
a result of decreased oxygen content in the blood as a result of
maternal diseases (diseases of the cardiovascular system, late
toxicosis, drop in partial pressure of oxygen in the inhaled air, acute
bilateral pneumonia of the mother, etc.).
• Intrapartum asphyxia - occurs during labor as a result of placental-
fetal (premature detachment of the placenta, placenta previa) or
placental-fetal circulation (prolapse of the umbilical cord from the
birth canal and pressing it between the wall of the birth canal and the
baby's head, tight wrapping of the umbilical cord around parts of the
fetal body, knots on the umbilical cord);
• Postnatal asphyxia - associated with the occurrence of lung diseases of
the child in the postnatal period.
In the pathogenesis of the development of the first two types of

asphyxia, the leading role is played by a sharp decrease in the level of
oxygen and a sharp increase in the level of carbon dioxide in the blood of the
fetus. This leads to irritation of the respiratory center of the baby at the
moment when it is intrauterine. The premature onset of respiratory
movements results in amniotic fluid, rather than atmospheric air, entering the
baby's lungs.
The main link in the pathogenesis of postnatal asphyxia lies in
disorders of the lung surfactant system. This is associated with premature
delivery of a premature baby. Premature babies have a low amount of
surfactant in the lungs. This amount of surfactant is able to support
spontaneous breathing for a while (2-6 hours). Once surfactant stores are
depleted, a condition called neonatal respiratory distress syndrome or
pneumopathy develops (see below). The pathogenesis of pneumopathies in
premature pregnancy is different.
254
it is associated with aspiration and inactivation of surfactant, as well as

t h e development of aspiration pneumonia in the lungs at a later time.
Acute hypoxia is manifested by sharply pronounced venous
hemorrhage of organs and tissues. Dark venous blood flows abundantly from
the surface of incisions. Microscopic examination reveals paralytically
dilated and full blood vessels.
Chronic hypoxia is manifested by two morphologic syndromes:
• dyscirculatory disorders:
- venous hyperemia;
- congestive edema, dropsy;
- hemorrhagic changes (in some cases, develops DIC).
• Alterative changes (dystrophy and necrosis).
In addition, a characteristic sign of intrauterine hypoxia is a greenish
staining of the fetal membranes, umbilical cord and amniotic fluid with
meconium.
► PNEUMOPATHIES NEWBORNS◄
Neonatal pneumopathies are non-inflammatory lesions of the
lungs of the newborn resulting in the development of neonatal
hypoxia.
The following types of neonatal pneumopathies are distinguished:

• neonatal atelectasis;
• Respiratory distress syndrome of newborns ("hyaline membrane
disease");
• edematous hemorrhagic syndrome;
• massive hemorrhages in the lung tissue;
• amniotic fluid aspiration;
• malformations (anomalies) of lung development;
• spontaneous pneumothorax, pneumomediastinum.
Clinical manifestations of respiratory distress syndrome:

• skin cyanosis;
• irregular, irregular breathing, often moaning;
• muscle atonia or hypertonicity;
255
• depression of the sternum, intercostal spaces, supraclavicular areas

during inhalation.
Pneumopathies develop during the first hours after delivery. In
different age groups, it is fatal in 20 to 85% of cases. When substitution
surfactant therapy with exogenous surfactant preparations is used, the
mortality rate is reduced to less than 10%.
Atelectasis
Atelectasis is a complete, active collapse of the respiratory portion of

the lung.
Atelectasis develops when there is no air in the airways due to

obstruction (obturation atelectasis) of the bronchial lumen or compression of
the bronchus from outside (compression atelectasis). It is also possible to
develop atelectasis due to damage to the anti-atelectatic surfactant, which
maintains the constancy of the shape and size of respiratory air spaces.
Primary and secondary atelectasis are distinguished:
• primary atelectasis - areas of lung collapse that did not expand after
birth, observed in stillborns. Macroscopically: undirected, flattened on
the posterolateral parts of the thoracic cavity, lungs occupying 1/3 of
the volume of pleural cavities, fleshy consistency, gray-blue or red-
blue color. If a fragment of such a lung is placed in water, it sinks, the
part of the lung containing air floats on the surface;
• secondary atelectasis - atelectasis that develops in the breathing lung
of a newborn as a result of a decrease in the volume of alveoli
(appearance of "collapsed" alveoli).
edematous hemorrhagic syndrome.
Edema-hemorrhagic syndrome - a violation of the permeability

of pulmonary capillaries due to their overflow of blood with the
development of diffuse edema and multiple hemorrhages in the
lungs.
256
This syndrome is often combined with hyaline membrane syndrome or

disease.
Respiratory distress syndrome (RDS) of newborns (hyaline membrane disease)
Respiratory distress syndrome is a severe respiratory disorder in

premature infants due to lung immaturity and primary surfactant
deficiency.
The phenomena of dystelectasis associated with the lack of surfactant

and the developing hypoxia lead to increased vascular permeability and
dystrophic-destructive changes in alveolocytes, which contributes to the
penetration of fibrinogen into the lumen of alveoli, coagulation of which
leads to the formation of fibrin. A layer of fibrin with an admixture of
cellular detritus covers the inner surface of the alveoli and blocks gas
exchange. In microscopic examination, the fibrin layer stains uniformly with
acidic dyes, i.e., it has tinctorial properties of hyaline. Therefore, fibrin
masses on the inner surface of alveoli in pathologic anatomy are usually
designated by the term "hyaline lung membranes".
Complications of pneumopathies:
• in 30% of cases, severe respiratory distress syndrome is complicated
by cerebral hemorrhage; the hemorrhage is of hypoxic origin;
• pneumonias that develop 1-2 weeks after pneumopathy;
• bronchopulmonary dysplasia;
• when performing ventilations - complications of resuscitation and
intensive care.
► BIRTH TRAUMA◄
Birth trauma is damage to fetal tissues and organs due to

mechanical birth forces.
Birth trauma should be distinguished from obstetric trauma, which

occurs as a result of assisted obstetric delivery.
257
ETHIOPATOGENESIS
During labor, the forces of uterine contractions and contractions of the
abdominal muscles act on the fetus. These forces help the fetus to move
through the birth canal. In 95% of cases, the birth is cephalopelvic, which
means that the fetal head is the first to move through the birth canal. Due to
the baby's head being squeezed by the walls of the birth canal, the bones of
the skull may become locked together (head configuration). If there is any
obstacle that prevents this movement, birth trauma occurs. The cause of birth
trauma is the mismatch between the birth canal of the mother and the size of
the fetus. Therefore, any abnormality on one side or the other can lead to
birth trauma:
• embryopathy;
• fetopathy;
• Prematurity - usually rapid preterm labor and as a consequence, the
birth canal is unprepared for the fetus;
• prematurity - dense skull bones, low birth weight, weak labor, etc.;
• pathology of the mother's birth canal - pelvic anomalies, tumors, scars,
etc.;
• Disruption of labor dynamics (high or low water, weak labor forces or,
on the contrary, rapid labor).
TYPES OF BIRTH TRAUMA
Skull injuries
They occur frequently, in 97% of all birth injuries:
• kephalohematoma - accumulation of blood (50 to 150 ml) under the
periosteum of the cranial bones. A kephalohematoma is delimited by
the bone because each cranial bone has its own periosteum;
• Fracture of the skull bones - may be accompanied by rupture of the
sinuses (usually rupture of the cerebellar plaque with formation of
subdural hematoma), development of epidural hemorrhages with
detachment of the dura mater;
• cerebral hemorrhage by rupturing a blood vessel.
A birth tumor, which occurs on the antrum of the fetus, is a congestive

hemorrhage and is not related to birth trauma; it disappears 1-2 days after
delivery.
258
Skeletal injuries
• Spinal fracture - the most typical localization is in the area of the 6-7
cervical vertebrae, when the child's head due to reasons preventing its
advancement, overextended, or vice versa, overbent;
• clavicle fractures;
• fractures of the femur and humerus, etc.
Injuries to internal organs are rare:

• lacerations of the spleen, liver, stomach;
• subcapsular hematomas;
• facial nerve paresis - as a result of its compression in the birth canal -
on the affected side, the nasolabial fold is smoothed, the eye is open,
there are no wrinkles on the forehead, the mouth is pulled to the
healthy side when screaming. The outcome is favorable.
► HEMOLYTIC DISEASE NEWBORN◄
Hemolytic disease of the newborn is a disease based on

hemolysis of the red blood cells of the fetus and newborn,
associated with incompatibility of the blood of the mother and
fetus on erythrocyte antigens.
ETHIOPATOGENESIS
Hemolytic disease of newborns develops mainly as a result of
incompatibility of the blood of mother and fetus by Rh factor (Rh-factor) or
group antigens, less often - by other antigenic systems due to their lower
immunogenicity.
• Rh-conflict occurs when an Rh-negative woman's fetus has Rh-
positive blood;
• AB0-conflict develops when the woman has blood type 0(I) and the
fetus has blood type A(II) (in 2/3 of cases) or B(III) (in 1/3 of cases).
The mother's blood produces antibodies to the Rh factor of the fetus,

and in the last weeks of pregnancy and during labor, antibodies from the
mother's blood enter the fetus's blood and cause massive hemolysis. In the
first pregnancy, this condition, as a rule, does not develop, because the
mother's body was not previously sensitized and the production of antibodies
is not so intense. With each subsequent pregnancy, the antibody titer
increases with great intensity.
259
Therefore, with each subsequent pregnancy, the risk of hemolytic disease

also increases.
As a result of massive hemolysis, a large amount of free bilirubin is
formed in the vascular bed. If the rate of hemolysis exceeds the conjugation
capacity of the liver, jaundice develops. When the level of bilirubin exceeds
300 μmol/L, the GEB becomes permeable for unbound bilirubin in the liver,
which reaches the brain, staining and damaging the subcortical nuclei of the
brain - the so-called nuclear jaundice (icterus nuclearis) occurs. Indirect
bilirubin is a tissue poison and therefore reduces metabolic processes in
tissues until the development of necrosis. Consequences of severe hemolytic
jaundice can be expressed in deviations in the psychoneurological status of
the child (cerebral palsy, hearing and speech disorders, etc.).
Congenital hemolytic disease can develop due to hereditary diseases in
which blood destruction is associated with genetic defects in red blood cells.
This is a group of hereditary hemolytic anemias (thalassemia, sickle cell
anemia, etc.).
The following are distinguished following clinical

and morphological forms
hemolytic disease of the newborn:
• edema is the most severe form and develops intrauterine.
Skin is pale, translucent, shiny,
macerated with petechial hemorrhages. Subcutaneous fatty
tissue and brain tissue in a state of pronounced edema, with
abundant transudate in the cavities.
The liver and spleen are sharply enlarged. Hypoplasia of the
thymus and lungs.
Foci of extramedullary hematopoiesis (erythroblastosis) in the

liver, spleen, lymph nodes, kidneys. In the liver, kidneys,
adrenal glands and brain - dystrophic-destructive
changes и
hemorrhaging.
• anemic form - skin and mucous membranes are pale, pasty. Spleen and
liver are slightly enlarged, with the presence of foci of
erythroblastosis.
• The jaundiced form is a severe postpartum form, accompanied by the
development of bilirubin encephalopathy with ganglion cell damage.
260
Jaundice (lemon-yellow skin coloration). Hepato- and

splenomegaly. The brain is edematous, jaundiced staining of
subcortical nuclei. The cortex and white matter are rarely
stained. The severity of brain damage is directly proportional to
the concentration of indirect bilirubin and
the duration of the bilirubinemia.
In the liver - "biliary stasis" as a result of bile thickening

syndrome; in the spleen - hemosiderosis. Focal pneumonia,
atelectasis, hyaline membranes. Hyperplasia of the bone
marrow. Kidneys - with blood bilirubin level over 500 μmol/l,
development of bilirubin infarcts of renal pyramids is possible.
Brain - signs of bilirubin encephalopathy.
261
SECTION XII
INTESTINAL INFECTIONS
Highest significanceи spread among Typhoid,

dysentery, cholera and salmonellosis are the most important and widespread
of the intestinal infections.
Intestinal infections - a group of diseases that are transmitted by

fecal-oral route and are characterized by symptoms of general
intoxication and gastrointestinal tract damage in the form of
gastritis, enteritis, colitis separately or in various combinations.
► BRUCE TIFF◄
Typhoid fever is an acute intestinal infectious disease belonging

to anthropozoonoses with fecal-oral transmission, characterized
by the development of symptoms of general intoxication, the
presence of fever and bacteremia, hepatosplenomegaly, enteritis
and stages of lesions of the lymphatic apparatus, mainly of the
small intestine.
ETHIOLOGY
The source of infection is most often people - chronic bacterial
carriers, who for years or even decades, remaining practically healthy, are
the source of infection. The causative agent of typhoid fever is Salmonella
typhi, which belongs to Enterobacteriaceae. The prevalence in the Russian
Federation is about 8 cases per 100 thousand population per year.
PATHOGENESIS.
В as main links pathogenesis abdominal of
the abdominal type are:
• the introduction of the pathogen into the body;
• the development of lymphadenitis;
• bacteremia;
• intoxication;
• parenchymatous diffusion;
• excretion of the pathogen from the body;
• formation of immunity and restoration of homeostasis.
After entering the digestive tract, Salmonellae in the lower of the of

the small of the small intestine penetrate в lymphatic
262
formations - aggregate (Peyer's plaques) and solitary follicles with signs of

inflammation (lymphadenitis) in them. Subsequently, the pathogen
penetrates into the mesenteric lymph nodes, where it multiplies and
eventually enters the bloodstream. The resulting bacteremia is accompanied
by the appearance of the first signs of the disease - intoxication and rash. At
the same time, a large amount of endotoxin is released, which has
pronounced effects on various organs and systems:
- neurotropic effect with the development of encephalopathy in the form
of lethargy of patients and confusion; the appearance of trophic
disorders in the structures of the intestinal wall (with the development
of flatulence, diarrhea, ulcerative defects of the mucous membrane);
- effect on the bone marrow - leukopenia;
- damage of cardiovascular system - dystrophic changes of
cardiomyocytes, and in severe cases - toxic myocarditis, infectious-
toxic shock with the development of cardiovascular failure.
After penetration of the pathogen into the bloodstream, it enters the
liver, where it multiplies for some time, and then is excreted with bile into
the intestinal lumen. Part of the pathogen is excreted with feces, and part is
re-infiltrated into the lymphoid follicles of the intestine.
CLASSIFICATION
Clinical classification typhoid typhoid fever
involves dividing it according to:
• clinical forms: typical form, atypical (abortive,
sterile) form;
• severity: mild, moderate, severe;
• cyclical, recurrent;
• presence of complications: uncomplicated, complicated;
• of the predominantly affected section: ileotif (small intestine [ileum]),
colotif (large intestine), ileocolotif.
The following periods are distinguished in the course of the disease:

• Elementary;
• in the middle of an illness;
• fading of the main clinical manifestations;
• recovery.
263
CLINICAL AND MORPHOLOGICAL MANIFESTATIONS

The incubation period is 9 to 14 days (7 to 25 days depending on the
number of microorganisms).
The beginning of the disease, usually 1-2 days, is characterized by the
gradual onset of general weakness, malaise, loss of appetite, headache,
worsening sleep. Subsequently, the temperature rises to 38-39.0°C.
On day 3-4 of the disease: skin pale, dry, characterized by relative
bradycardia, adynamia, mild stunned. The abdomen is significantly
distended, slightly painful. The tongue is slightly increased in volume,
covered with dirty gray plaque on the back. Since the 4-5th day there is an
increase in liver and spleen. Blood picture: lymphocytosis, leukopenia due to
neutropenia, aneosinophilia; sedimentation 20-25 mm/h.
On the 8th-10th day - on the skin of the upper abdomen, less often - of
the lower chest, appears a rash (roseola) in the form of pink spots up to 3-4
mm in diameter with clear boundaries, slightly elevated above the skin level,
disappears when pressing for a short time. Increasing fever, headache and
insomnia.
Microscopic examination of rozeols - loosening of epidermis
with hyperkeratosis, in the papillary layer of dermis there is
hyperemia of vascular bed and
focal lymphoid infiltration.
In the 3rd week of the disease - complications of the disease may

occur: intestinal bleeding, perforations with the development of peritonitis,
etc. (see below). (see below)
After the 4th-5th week - a tendency to normalization of temperature,
decrease and disappearance of intestinal manifestations (convalescence
period).
Stool in typhoid fever in the form of "pea soup" - abundant, turbid,
frothy with a greenish tinge.
The peculiarity of intestinal lesions in typhoid fever is the presence of
five pathognomonic morphologic stages depending on the age of the disease.
Each stage takes approximately one week.
The "brain-like" swelling stage
The first stage (1st week of the disease), the "brain-like" swelling stage, is
characterized by a dramatic increase in the size of group (aggregate)
lymphatic follicles.
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Increase in the size of group (aggregate) lymphatic follicles;

they have dense consistency, protrude into the intestinal lumen.
Their surface is relief, with furrows, resembles the surface of
the cerebral hemispheres. On the section gray-pink color.
Intestinal mucosa is hyperemic, edematous,
covered in mucus.
Edema and hemorrhage of the intestinal mucosa, infiltration

with neutrophils. Large lymphatic follicles with clusters of
histiocytes, reticular cells and large macrophages with broad
eosinophilic cytoplasm are present in the intrinsic lamina of the
mucosa. Large light-colored macrophages in their cytoplasm
contain peritoneotyphoid bacilli. Macrophages form clusters
(peritoneal typhoid bacilli
granulomas).
Necrosis stage - the second stage (2nd week of illness) is necrosis of

hyperplastic group lymphoid follicles (Peyer's plaques), particularly
granulomas.
Starting from the mucosa and submucosa, the necrosis deepens,
invading the muscular layer and sometimes reaching the
peritoneum. In the periphery there is demarcation inflammation.
Dystrophy of nerve fibers and ganglia located in the
of the intestinal wall. In mesenteric lymph nodes - formation of
abdominotyphoid granulomas.
The stage of ulceration with the appearance of "dirty" ulcers - 3rd week of
the disease.
stage formation stage "dirty" ulcerscharacterized by
necrotic masses and ulcer formation.
Separation of necrotic masses from the surface of the ulcer

defect с exposure the underlying tissue. В
mesenteric lymph nodes - necrosis.
The stage of "clean" ulcers - 4th week of the disease. There is a "cleansing"
of ulcers from necrotic detritus.
The ulcers stretched out along of the intestine,
have flat, slightly
rounded edges, bottom with insignificant striation, due to the
fact that it is formed by the muscular sheath.
Necrotized tissues on on the surface on the

surface of the ulcer. В at the bottom и edges
ulcerous defect. -
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overgrowth granulation tissue с leukocytic

macrophage infiltration.
Ulcer healing stage - 5-6 weeks of the disease
Healing of ulcer defects with the formation of delicate
of rubes.
In the bottom and edges of the ulcer defect - overgrowth of

granulation tissue with lymphocytic-macrophage infiltration.
Phenomenon of epithelium "filling" - hyperplasia of epithelium
in the edges of the ulcer with subsequent epithelization of the
ulcer defect. Formation of new
lymphoid follicles.
The mesenteric lymph nodes show the development of the same

changes and in the same sequence as in the peyer's plaques, up to necrosis,
but with a lag of about 1 week. Subsequently, their organization and, in some
cases, calcification are noted.
In typhoid fever, the spleen is enlarged 3-4 times, its capsule is tense;
the tissue is dark red in color on section, gives abundant scraping of the pulp.
Microscopically, hyperplasia of red pulp and formation of typhoid
granulomas are observed.
Thus, in the development and course of the disease, can be observed:

• the general changes characteristic of typhoid fever:
- typhoid exanthema;
- Brucetophilic granulomas predominantly in the liver, spleen, lymph
nodes, bone marrow, lungs, gallbladder, and kidneys;
• general changes common to any infectious disease:
- hyperplasia of the spleen and lymph nodes;
- dystrophic processes in parenchymatous organs.
A distinction is made between intestinal and extraintestinal complications, as
well as specific and non-specific complications. They can also cause the
death of the patient.
• Specific complications:
- Intestinal bleeding (1-2%) - most often observed in the stage of
"clean" ulcers;
- ulcer perforation (0.5-1.5%) with the development of peritonitis -
also
266
is most commonly seen in the "clean" ulcer stage, but can also
occur in the necrosis and "dirty" ulcer stages;
- infectious-toxic shock - most often develops during the height of
the disease (2-3 weeks).
• Non-specific complications: pneumonia, bronchitis, meningitis,
myocarditis (up to 98% в in case of death
patients), mumps,
cholecystocholangitis thrombophlebiti purulent arthritis,
, pyelonephritis, s, infectious psychosis, lesion
peripheral of the osteomyelitis, intramuscular
nerves,obstruction, etc.
abscesses, sepsis, intestinal
There may also be wax-like necrosis of the rectus abdominis muscle.
muscles anterior abdominal wall abdomenor anterior
surface of the thigh, purulent perichondritis of the larynx (so-called
"laryngotitis"). У 3-5% of individuals who have contracted
with typhoid typhoid fever can chronic bacterial carrier, which
lasts for many years, and in some cases - for life.
► DESCENTERIA◄
Dysentery or shigellosis (from Greek dys - disorder and enteron -

intestine) is an acute anthroponotic infectious intestinal disease
with fecal-oral mechanism of transmission, predominantly
affecting the large intestine and intoxication phenomena of
neurotoxicosis type.
ETHIOLOGY
Dysentery is caused by bacteria of the genus Shigella (Shigella
dysenteriae [Grigoriev-Shigi], Shigella flexneri [with subspecies Newcastle],
Shigella zonae, Shigella boyd). The only source of infection is a sick person.
The mechanism of entry of infection is fecal-oral, and the routes of
transmission are water, food, and household contact. The reproduction
process of shigellae is accompanied by the accumulation of thermostable
endotoxin. Shigella also produce exotoxin, which has
pronounced neurotoxic, as well as enterotoxic and
cytotoxic effects.
PATHOGENESIS.
The incubation period for acute dysentery ranges from 1 to 7 days.
Bacteria develop in the epithelium of the mucous membrane of the large
intestine. In the process of life activity shigellae have cytopathic effect on the
intestinal epithelium, which is manifested by destruction and desquamation
of the intestinal mucosa epithelium
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and the development of so-called desquamative colitis. The enterotoxin

released during the destruction of shigellae has a vaso-neuroparalytic effect,
which leads to the development of paretic dilation of blood vessels and
damage to intramural nerve ganglia of the intestine.
In the pathogenesis of dysentery can be distinguished two phases:
small intestinal and large intestinal. Depending on the severity of these
phases, there are different features of the course of the disease.
• small intestinal phase - shigellae attach to enterocytes of the small
intestine and begin to produce cyto- and enterotoxins, and after death,
endotoxin is released from the bacteria with the development of
symptoms of intoxication;
• colonic phase - shigellae adhere on the surface of the mucosa (more
often in the rectum and sigmoid colon) with subsequent invasion into
the epithelial cells and submucosal layer of the intestinal wall, where
they multiply. The beginning of the inflammatory process is associated
with the synthesis of Shigella hemolysin, enterotoxin, endotoxin. The
action of toxins is accompanied by disorders of intestinal function,
hemodynamic disorders, the development of serous edema and
destructive-necrotic processes in the mucosa.
Inflammation, in the early stages, is usually catarrhal in character, and
later - fibrinous.
CLASSIFICATION
A distinction is made following clinical
and morphologic forms of the disease:
• acute dysentery:
-typical (varying degrees of severity);
-atypical (gastroenterocolitic);
- subclinical;
• chronic dysentery:
- recurrent;
-continuous (protracted);
• "post-dysenteric" dysfunctions intestinal dysfunction
("post-dysenteric" colitis).
It is also possible to classify dysentery according to the nature of the

lesion of the mucosa of the colon:
- catarrhal colitis;
- Fibrinous colitis (more often diphtheritic, less often croupy);
- ulcerative colitis.
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Clinical manifestations in dysentery are quite diverse. This is due to
different factors that may vary in a particular patient: the type and
pathogenicity of the microorganism, initial state of health, timing of the start
of treatment, etc.
There are several clinical variants of the course of dysentery:
• colitic variant - characterized by an acute onset with increased body
temperature, intoxication. There are contraction-like pains in the
abdomen. Stool at an early stage of the disease is frequent, liquid; in
the future - the volume of stool decreases, it becomes scanty, greenish
in color, with a large amount of mucus. At later stages - in the stool
may appear streaks of blood or pus ("stool like rectal spit");
• gastroenterocolytic variant - short incubation period (6-8 hours). Early
stages resemble a food toxic infection: increased body temperature,
nausea, vomiting, abdominal pain, abundant liquid stools without
pathologic impurities. On the 2-3rd day - the appearance of signs of
enterocolitis: mucus appears in the feces, sometimes with streaks of
blood, their number decreases, pain localized in the area of the
sigmoid and rectum;
• gastroenteritic variant - the clinic is similar to food toxicoinfection or
salmonellosis: frequent liquid stools, repeated vomiting with
dehydration. Unlike other forms of dysentery, this form does not
involve the large intestine;
• sterile course - frequency of stool 1-2 times a day, fecal masses of
mushy consistency, pathological impurities may be absent, subfebrile
temperature. Microscopic changes correspond to moderately
pronounced catarrhal inflammation of the mucous membrane;
• chronic dysentery - if the symptoms of the disease persist for more
than 3 months. It is characterized by the presence in the anamnesis
indication of dysentery in the last 6 months. Flows in the form of two
variants:
- recurrent variant - in case of recurrence, clinical and morphological
manifestations are characteristic of the acute form of the disease.
Often the picture of the colon is characterized by "mosaicism":
alternation of affected areas of the mucosa with atrophied or little
changed areas;
269
- continuous variant - occurs rarely, characterized by constant

progression with slightly pronounced signs of intoxication.
INTESTINAL MORPHOLOGY
Morphologic changes develop in the mucosa of the distal parts of the
colon (mainly in the rectum and sigmoid colon).
In the development of dysenteric colitis, 4 stages are distinguished:
• catarrhal colitis stage;
• stage of fibrinous colitis;
• The stage of ulcer formation (ulcerative colitis);
• the healing stage of the ulcers.
The catarrhal colitis stage is the first 2-3 days of the disease:
The lumen of the intestine is narrowed due to spasm of the
muscular layer, full blood and edema of the mucosa, small
hemorrhages and small superficial spots
necrosis.
Desquamation of intestinal epithelium, signs of edema and

hemorrhage. In the intestinal wall (in the mucosa and
submucosa layer) - focal lymphocytic-leukocytic
infiltration, small foci of mucosal necrosis and hemorrhages.
The stage of fibrinous colitis (5-10 days of the disease) is characterized by

the appearance of fibrin film on the surface of the mucous membrane. More
often the inflammation is diphtheritic in nature (depending on the depth of
necrosis).
Thickening wall и narrowing lumen of the
intestine; on
a brownish-green colored film is visible on the surface of the
mucosa.
Edema, fulminant hemorrhage, areas of necrosis of the colonic

mucosa. Perifocal inflammation with predominance of
leukocytes in the infiltrate. Dystrophic and necrotic changes in
nerve plexuses
nerve cells (disintegration of nuclei, vacuolization and
subsequent lysis of cell cytoplasm, disintegration of nerve
fibers).
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Ulcer formation stage - develops on the 10th-12th day of the disease. Ulcer
formation is associated with the rejection of fibrinous films and necrotic
masses underneath them.
Occurrence of ulcers is observed most often in the rectum and
sigmoid colon. Due to the different depth and volume of
necrosis, the ulcerated mucosal defects formed have a
irregular shapes and varying depths.
Depth necrosis can reach muscular or

serous layer, therefore formation ulcerscan
be accompanied with the appearance bleeding,
perforations of the intestinal wall and
peritonitis.
Ulcer healing stage - 3-4 weeks of the disease. At this stage, regeneration of
the colonic mucosa occurs due to filling of ulcer defects with granulation
tissue and their subsequent epithelialization.
Depending on the size of the ulcers, healing can be:

• complete (in small and shallow ulcers) - complete
restoration of the structure and function of the intestinal
wall;
• incomplete (in the area of large and deep ulcers) - with
the formation of scar tissue.
Features of dysentery in children are more frequent development of

catarrhal colitis, follicular colitis and follicular ulcerative colitis.
In follicular colitis there is increase in
solitary follicles, and they protrude above the
by the surface of the mucous membrane.
In some cases, necrosis of the central parts of follicles with

subsequent purulent melting and formation of ulcerative defect
occurs
of the mucosa - that's what follicular ulcerative colitis is.
Changes in other organs and tissues

The development of parenchymatous fatty dystrophy in the liver and
myocardium is noted. Spleen slightly increases in size due to hyperplasia of
lymphoid cells. It is possible development of small focal necroses in the
liver. In kidneys - protein dystrophy
271
epithelium of distal and proximal tubules. In severe intoxication or

dehydration may be observed necrosis of the epithelium of the proximal
tubules (necrotizing nephrosis).
Complications of dysentery are commonly divided into intestinal and
extraintestinal complications:
• intestinal complications:
-perforation of the ulcer with the development of peritonitis,
paraproctitis, retroperitoneal phlegmon;
-intestinal bleeding;
-phlegmon of the intestine;
-rubic intestinal stenosis;
-severe dysbiosis;
-postdysenteric colitis;
-paresis or intestinal intussusception;
-cracks and erosions of the anus;
- hemorrhoids;
-lapse of the rectal mucosa;
-persistent dysbiosis;
• extraintestinal complications:
-pneumonia (bronchopneumonia);
- infectious toxic shock;
- pyelonephritis;
-pylephlebitic liver abscesses;
-hypovolemic shock (more common in young children);
-aseptic serous arthritis;
-in chronic course - amyloidosis, emaciation;
-purulent (shigellosis) meningitis, meningoencephalitis, brain
abscess.
► AMEBIAZ◄
Amoebiasis (amoebic dysentery) is a chronic disease of protozoal

etiology characterized by the development of chronic recurrent
ulcerative colitis.
ETHIOPATOGENESIS
Amoebiasis is caused by the dysenteric amoeba (Entamoeba
histolytica). It occurs mainly in countries with hot climates. The route of
transmission is alimentary, fecal-oral,
272
waterborne, contact and household contact. A person becomes infected when

amoeba cysts enter the digestive system. As a rule, the cyst melts in the
cecum, and the amoeba penetrates the intestinal wall. A microabscess forms
in the submucosal layer in the zone of penetration, which subsequently bursts
into the intestinal lumen.

The incubation period is from 1 week to 3 months. Symptoms of the
disease: liquid stools with vitreous mucus and blood, subfebrile, abdominal
pain, weakness, headache. The course of the disease is characterized by
alternating exacerbations and remissions. In the case of a prolonged course
of the disease, a decrease in body weight is observed, hypochromic anemia
may develop.
After penetration of the amoeba independently and due to excreted
products of life activity affects the tissues of the intestinal wall, leading to
local disorders in the form of edema, necrosis of the mucosa, formation of
ulcerative defects. These changes are most pronounced in the cecum,
although they can occur throughout the large intestine, and occasionally in
the ileum.
On the mucosal surface there are deep ulcers with undermined
edges, usually not more than 10 mm in diameter. The ulcerative
defects are surrounded by a corolla-like area
hyperemic mucosa; purulent plaque is visible at the bottom.
Penetration of the necrosis zone into the submucosa and muscle

layer. Amoebae can be found at the border between necrosis
and preserved tissues. As they become attached
secondary (intestinal) infection, significant perifocal
neutrophilic infiltration appears.
In small, superficial ulcers, complete regeneration is possible, but more often
there are deep ulcers that heal with scarring.
Complications:
• intestinal (perforation of the ulcer with the development
of peritonitis, bleeding, scar stenosis, etc.);
• Extraintestinal (with hematogenous spread - abscesses of the
liver, lungs, brain, etc.).
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► CHOLERA◄
Cholera is an acute infectious disease from the group of

particularly dangerous infections, manifested by acute
gastroenteritis, diarrhea, vomiting and excystosis (dehydration of
the body).
ETHIOLOGY
Three types of pathogens are distinguished:
• vibrio cholerae asiaticae (causative agent of classical cholera);
• vibrio cholerae eltor (the causative agent of El Tor cholera);
• serovar O139 (Bengal) (causative agent of cholera in Southeast Asia).
Cholera is a strict anthroponosis - only people get sick. The vibrio
usually enters the body with contaminated water or food. The cholera
pathogen is very sensitive to acids, particularly hydrochloric acid in gastric
juice.
PATHOGENESIS.
Three components of the "toxicity" of cholera vibrio can be
distinguished:
- vibrios secrete exotoxin - cholerogen - the most important
pathogenetic factor;
- endotoxins are released when microbial bodies are broken down;
- permeability factor - a group of enzymes that promote increased
permeability of the vascular wall of cell membranes and
contribute to the action of cholerogen.
Exposure of exotoxin (cholerogen) to the intestinal wall leads to both

impaired fluid absorption and active fluid secretion into the intestinal lumen.
This leads to secretion into the intestinal lumen of isotonic fluid with low
protein content in the volume of up to 1 l/h, which clinically corresponds to
the appearance of profuse diarrhea (up to 10-20 l/day and more) with
massive and rapid loss of electrolytes. Rapid fluid loss is accompanied by
blood concentration, increase in its viscosity, slow blood flow in capillaries,
the appearance and growth of circulatory hypoxia, which causes the
development of dystrophic-necrotic processes in organs, primarily in the
brain, heart and kidneys.
Common clinical manifestations:

• the onset is acute;
• the first symptom is liquid stools;
274
• the urges are imperative;
Features of diarrheal syndrome:

• the temperature's not rising;
• no pain syndrome;
• no flatulence (retracted abdomen);
• no intoxication;
• defecation resembles the appearance of rice broth (whitish,
sometimes with a yellowish tinge, with flakes, watery stools);
• followed by vomiting.
CLASSIFICATION
A distinction is made between classical cholera and El Tor cholera,
characterized by a milder course and lower mortality.
Three periods are distinguished in the course of cholera:
• acute enteritis;
• acute gastroenteritis;
• algid (cold) period - does not develop in all cases (it is
believed that it does not develop when infected with Vibrio
cholerae eltor).
A distinction is also made between typical and atypical forms of the disease:
• The typical form is enteritis followed by gastritis + dehydration;
• atypical form - changes are insignificant, subtle, dehydration
practically does not develop. Lightning or "dry cholera" is also
considered an atypical form.
1- й period - acute catarrhal (cholera) enteritis -

duration 1-2 days.
Edema of the intestinal mucosa, dilation of blood vessels with
single or multiple hemorrhages; in the lumen of the intestine - a
large amount of fluid type
"rice broth" with a "fishy odor."
The wall of the small intestine is sharply edematous, with

dilated blood and lymphatic capillaries, petechial hemorrhages;
vacuolization of epithelial cells of the
mucosa. Inflammatory
infiltration is insignificant and is represented by
275
predominantly by plasmacytes. The intestinal villi

appear devoid of epithelium, which is preserved
only in the depths of the crypts.
In El Tor cholera, unlike classical cholera, intestinal damage is
characterized by the development of serous hemorrhagic enteritis.
Microscopically, pronounced edema of the mucous membrane, hyperemia of
intestinal villi vessels, and hydropic dystrophy of enterocytes are observed.
In El Tor cholera the so-called abortive form is possible - at this point the
course of the disease may stop.
2- period - cholera gastroenteritis - duration 1-1.5 days, but during this time
the patient can lose up to 30 liters of fluid. The phenomena of dehydration
increase, blood clotting occurs, increase in the amount of protein, metabolic
acidosis progresses. During this period, serous or serous-hemorrhagic
enteritis is joined to serous or serous-hemorrhagic gastritis.
Dehydration phenomena associated with massive fluid loss due
to vomiting and diarrhea: cyanosis, drop in blood pressure, drop
in body temperature, and
the amount of urine you excrete.
Microscopically - further progression of lesions of intestinal

wall elements - partial desquamation (sloughing) of both
microvilli on the surface of epithelial cells, and the very
epithelial cells into the intestinal lumen.
3- The algid period (from algor - cold). This is the period of the disease, in
which the leading manifestations of excicosis (dehydration). Loss of fluid
and electrolytes, especially Na+, contributes to the increase in acidosis and
the development of convulsions. The appearance of the patient is
characteristic: apathy is observed, facial features are sharpened, eyes are
deeply sunken into the eye sockets, the skin becomes dry, wrinkled, covered
with cold clammy sweat. The most pronounced changes in the skin of the
hands because of what this sign has been called "washerwoman's hands".
Due to dryness of the mucous membranes of the larynx and vocal cords,
hoarseness of the voice is observed - so-called vox cholerica.
In connection with the growing phenomena of hypovolemic shock
there are signs of impaired renal filtration in the form of oligo- and anuria
with the subsequent development of nephrotic necrosis (clinically manifested
by acute renal failure).
276
Classification by degree of dehydration:

• 1 degree - the patient's body weight deficit is 1-3%;
• Grade 2 - 4-6% deficit;
• Grade 3 - 7-9% deficit;
• Grade 4 - deficit of 10% or more - the fourth degree is
hypovolemic (dehydration) shock.
The appearance of the corpse is characteristic, due to exicosis:

• "dried" corpse with bent limbs and toes (so-called "gladiator's pose");
• early and long-lasting rigor mortis;
• mucous membranes, subcutaneous tissue and muscles are dry,
dark in color;
• vessels contain a small amount of thick, dark blood in their lumen.
Cholera is characterized by spleen shrinkage and shriveling of its

capsule; microscopically, there is a decrease in the size of follicles and signs
of hemosiderosis. Serous membranes - with multiple petechial hemorrhages.
On the serous membranes and between the intestinal loops, sticky deposits
are seen, stretching in the form of threads.
Stretching of the small intestine loops with a large amount of

fluid in the form of "rice broth" + sharply enlarged
gallbladder, which contains a large amount of colorless bile
("white bile") in its lumen
Sharp signs of full blood vessels, stasis, edema, especially in

intestinal villi, necrosis and desquamation of epithelium of
small intestine villi, hemorrhages, infiltration of mucosa and
partially submucosal layer with lymphocytes, macrophages,
single neutrophils; in addition, there are dystrophic in
intramural ganglia.
changes. There are signs of moderate hyperplasia of solitary
lymphoid follicles.
In the internal organs - liver, myocardium, central and peripheral

nervous system, signs of dystrophy and necrobiotic changes are found
everywhere, and very characteristic is the pathology of the kidneys in the
form of necrosis of the epithelium of the proximal tubules (necrotizing
nephrosis).
277
In addition to the typical forms of cholera, there is also an atypical

form, the so-called "dry" or lightning form, which develops in weakened
patients and can lead to death from cardiovascular failure in a few hours
from the onset of the disease even before the appearance of a typical clinical
picture (diarrhea or repeated vomiting).
The course of cholera can be complicated by the development of specific and
nonspecific complications.
Specific complications:
• cholera typhoid - associated with repeated entry of vibrio into the
human body against the background of already existing high
sensitization to it, or against the background of activation of intestinal
flora in conditions of pronounced decrease in immunity.
Manifestations largely resemble the clinic of typhoid fever (hence the
name) - nausea, vomiting, skin rash, liquid stinky stools, sharply
elevated temperature, impaired consciousness; in some cases may
occur diphtheritic sore throat, gastritis, cystitis. Manifestations
characteristic of the algid period, in cholera typhoid disappear.
Mortality may reach 80-90%;
• Postcholera uremia is a complication arising after the algid period of
cholera. Morphologically, there are multiple infarct-like areas of
necrosis in the renal cortex;
Nonspecific complications:
• pneumonias, phlegmons, abscesses, sepsis - arise due to the activation
of autoinfection against the background of reduced immunity in a
weakened patient;
• hypovolemic shock;
• acute renal failure, oligo- and anuria;
• CNS dysfunction with the development of convulsive syndrome and
coma.
The death of patients occurs, as a rule, in the algid period from exicosis
(dehydration), coma, infectious-toxic shock and complications.
The immediate causes of death in cholera can be considered:

• cholera coma;
278
• acute heart failure;

• pulmonary embolism;
• pneumonia.
► SALMONELLES◄4↩
Salmonellosis is an acute intestinal infectious disease caused by

salmonellae of various species.
ETHIOLOGY
The causative agent is flagellated gram-negative bacilli, salmonella of
various species (Salmonella typhimurim, Salmonella enteritidis, Salmonella
cholerae souis, Salmonella parattyphi A and Salmonella Schottmulleri). The
pathogen can persist for a long time (up to several months) in the external
environment and foodstuffs (most often - meat of animals, birds, chicken
eggs). The source of infection is a sick person or bacterial carriers. The route
of transmission is most often alimentary (food), less often waterborne,
contact, and rarely airborne.
PATHOGENESIS.
The mucosa of the small intestine serves as the entry gate of infection.
Salmonellae penetrate the epithelial cells of the mucosa or macrophages,
where they can multiply. Released during the decay of salmonella endotoxin
has vasoparalytic, pyrogenic and cytotoxic effects, which determines the
variety of damage to organs and systems of the human body. It is possible
penetration of salmonellae in the bloodstream with the emergence of a
generalized form of the disease, and in the so-called septic form of the
pathogen with the bloodstream carried into the organs, with the subsequent
formation of foci of purulent inflammation. Severe course may be
complicated by the development of vascular collapse, exicosis or infectious-
toxic shock.
CLASSIFICATION
The following forms of the disease are distinguished:
• Gastrointestinal (toxic) form:
-gastric variant;
-gastroenteric variant;
-gastroenterocolytic variant;
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• generalized form:
-typhoid version;
-septicopiemic variant.
The incubation period lasts from several hours to 3 days (more often
12-24 hours). Clinical manifestations of salmonellosis are more
characterized by an acute (sudden) onset of the disease. In adults and
children older than 3 years disease manifests itself by the
development gastritis, gastroenteritis often proceeding by the type of food
toxicoinfection. В depending on depending on the causative
agent, there are certain clinical peculiarities,
such as when infection with Salmonella parattyphi A is often
characterized by cough, runny nose, sore throat, while Salmonella
Schottmulleri or Salmonella cholerae souis is characterized by nausea,
vomiting, abdominal pain, diarrhea; since this clinical picture is extremely
similar to cholera, this form of Salmonellosis is often called domestic
cholera (cholera
nostras).
Leading syndromes in acute intestinal include:
• gastroenteritis;
• intoxication;
• painful;
• dehydration;
• demineralization.
Depending on the lesion of one or another part of the gastrointestinal tract
is distinguished:
• gastritis;
• gastroenteritis;
• enterocolitis;
• gastroenterocolitis;
• colitis.
MORPHOLOGICAL CHANGES
Intestinal form - there is a pattern of acute
gastroenteritis.
Increased diameter of the intestine due to paretic dilatation of its

lumen. The intestine contains greenish semi-liquid fecal masses
with an admixture of mucus and a pungent putrefactive odor.
There is hyperplasia of lymphoid tissue
of the intestinal apparatus. When infected with Salmonella
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typhimurim and Salmonella enteritidis are predominantly

affecting the cecum in the form of multiple lesions.
mucosal erosions.
In the wall of the intestine and stomach - signs of catarrhal

inflammation, often with a pronounced hemorrhagic component
(depending on the degree of disruption of the vascular wall).
The mucous membrane of the stomach, small intestine - with
signs of marked edema, hemorrhage, small hemorrhages,
erosions and small
acute ulcers. The serous membrane of the intestine is full-
blooded, with small hemorrhages.
Septic form (septicopoietic variant). The morphological picture of the

intestine practically repeats the changes in the intestinal form, but due to the
generalization of the process, patients have abscesses of metastatic nature in
the lungs, brain and others.
Typhoid fever. The inflammatory changes are similar to typhoid fever. In

this form, bacteremia, fever and chills are observed in the first week. In the
second week a skin rash appears, abdominal pain, etc. is noted. The third
week is characterized by the appearance of changes similar to those in
typhoid fever in the intestine, lymph nodes, spleen. Hyperplated Peyer's
plaques may ulcerate with the development of intestinal bleeding.
Complications: toxic-infectious shock, purulent complications. Prognosis. В
in most cases there is recovery.
Some patients develop chronic bacterial carriage in all clinical
variants of the course.
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SECTION XIII.
AIRBORNE INFECTIONS
Airborne infections are a group of acute inflammatory diseases

with lesions of different organs and tissues that determine their
characteristics.
There are the following common features that allow these diseases to
be grouped together:
• airborne transmission;
• pronounced local changes, combined с general
manifestations;
• a propensity for epidemics;
• high prevalence of disease regardless o f age and gender.
The following is a generalized classification of respiratory infections,
mainly in children:
Etiology • viruses (influenza, parainfluenza, respiratory
syncytial virus, adenovirus, rhinovirus,
reovirus, enteroviruses, coronaviruses,
metapneumovirus,
bocavirus, herpes simplex virus,
cytomegalovirus);
• bacteria;
• mushrooms
By time of occurrence • congenital;
• acquired (postnatal)
By clinical form (type) • typical;
• Atypical (asymptomatic, sterile)
By severity. • mild form;
• medium-severe form;
• severe form
By clinical and • rhinitis;
morphological form of • rhinoconjunctivitis;
respiratory tract lesions • sinusitis;
• otitis media;
• pharyngitis;
• tonsillitis;
• epiglottitis;
• Laryngitis (nonobstructive,
obstructive [croup]);
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• tracheitis;
• bronchitis;
• bronchiolitis;
• pneumonia
Downstream • uncomplicated;
• complicated
Specific complications Febrile seizures, cerebral edema and swelling.
(virus associated) brain (neurotoxicosis),
meningoencephalitis, Guillain-Barré syndrome
(demyelinating polyradiculoneuritis), auditory
neuritis, myocarditis, hemorrhagic syndrome,
segmental pulmonary edema, bronchiolitis
obliterans, syndrome of
Rhea, hemolytic uremic syndrome.
Bacterial complications Mastoiditis, labyrinthitis, facial nerve paresis,
meningitis, brain abscess, sepsis, cervical purulent
lymphadenitis, paratonsillar and pharyngeal
abscesses (complications of otitis media),
rheumatic fever, acute glomerulonephritis
(complication
s of streptococcal tonsillitis), phlegmon of the
orbit, meningitis, brain abscess, sepsis,
mediastinitis, pleurisy
Non-specific Exacerbations of chronic respiratory diseases
complications (bronchial asthma, bronchopulmonary dysplasia,
cystic fibrosis, tuberculosis) and
somatic (diseases of the urinary system,
rheumatism, cholecystitis, etc.) diseases
Among these diseases, acute respiratory viral infections (influenza,

parainfluenza, adenovirus and respiratory syncytial infection) and bacterial
infections (diphtheria, scarlatina, meningococcal infection) are particularly
relevant.
► GRIPP◄
Influenza is an acute, highly contagious epidemic disease caused

by an RNA virus that is tropic to the respiratory epithelium.
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ETHIOLOGY
There are 3 serologic types of influenza virus:
• A (poses the greatest epidemic risk);
• B (causes localized outbreaks and epidemics);
• C (results in generally sporadic cases). Specific
lipoglycoprotein receptors (capsids)
provide fixation of the virus on the surface of epithelial cells.
PATHOGENESIS.
The virus causes 3 stages of the disease:
• Stage 1 is the introduction and initial reproduction of the virus, which
is accomplished by its RNA polymerase. The duration of this stage,
corresponding to the incubation period of the disease, ranges from a
few hours to 2-4 days;
• Stage 2 - virusesemia, accompanied by prodromal phenomena;
• Stage 3 - secondary reproduction of the virus in trophoblast cells,
leading to generalization of the infection and the onset of the disease.
The developing changes in the body are due to the following
properties (action) of the virus:
• cytopathic (cytolytic) action - leads to dystrophic lesions of respiratory
epitheliocytes with subsequent necrosis, desquamation, which is often
accompanied by impaired drainage function of respiratory epithelium;
• immunosuppressive effect - with the development of transient
immunodeficiency, manifested in a significant decrease in the patient's
phagocytic activity of neutrophils, macrophages, suppression of
chemotaxis, the appearance of circulating toxic immune complexes;
• vasopathic (vasoparalytic) action - causes hyperemia, stasis, plasma
soaking, edema, plasmorrhagia and hemorrhage;
• neuropathic action - due to the impact, primarily on neurovegetative,
neuroendocrine and neurohumoral centers of the medulla oblongata
and hypothalamus, where high concentration of toxins is created due
to large vascularization.
Depending on the degree of severity and clinical and morphological
manifestations, three forms of influenza are distinguished:
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• mild form - runs for one week and ends with full recovery. The most
frequent variant of the course (form) of the disease;
• medium severity form - characterized by damage to small bronchi,
bronchioles and lung parenchyma. The duration of the course of
influenza of medium severity is about one month. Usually ends with
full recovery;
• severe form:
- with pronounced severe intoxication - cytopathic and vasoparalytic
action of the virus takes the first place;
- with pulmonary complications - characterized by the accession of
secondary infection, which causes all the major changes. Among
the causative agents of secondary infection, the first place is
occupied by staphylococcus, then streptococcus and pseudomonas
bacillus. The main changes develop in the bronchial tree and
pulmonary parenchyma.
MILD FLU
В lumen upper respiratory tract in the lumen of the
upper respiratory tract is serous, serous-mucous exudate.
Acute catarrhal inflammation in the upper respiratory tract.

Dystrophy of epithelium with vacuolization of cytoplasm,
desquamation of cells and formation in the lumen of small
bronchi of clusters of descended cells. In the mucosa
the sheath - full blood vessels, small hemorrhages, edema,
focal lymphohistiocytic infiltration.
MILD-TO-MODERATE INFLUENZA
In the bronchial mucosa - serous hemorrhagic inflammation.
Necrosis and desquamation of epithelium with the formation of

foci of atelectasis and pulmonary emphysema. In segmental
panbronchitis inflammation (peribronchial) passes to the
adjacent lung tissue, in which there are foci of influenza
pneumonia: in alveoli serous-hemorrhagic exudate, sloughing
of cells
of the alveolar epithelium. In the interalveolar septa.
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- interstitial (interstitial) inflammation represented by

lymphohistiocytic infiltrates. Inflammatory changes in the
lungs are combined with
signs of bronchial and alveolar epithelial regeneration.
SEVERE FLU
Form with severe severe intoxication - in the trachea and
bronchi expressed serous hemorrhagic inflammation and
necrosis. In the lungs - circulatory disorders, hemorrhages,
small foci of serous hemorrhagic pneumonia + general
intoxication manifested by small multiple hemorrhages in the
brain, internal organs, serous and mucous membranes.
Influenza with pulmonary complications - in the bronchi
serous-purulent inflammation, destructive panbronchitis is
characteristic. Due to the destruction of the bronchial wall may
be the formation of acute bronchiectasis, foci of atelectasis and
acute emphysema. In influenza bronchopneumonia lungs are
enlarged in size, on the section
mottled ("large mottled flu lung").
In alveoli - serous-hemorrhagic exudate with admixture of a

large number of neutrophilic leukocytes, sometimes areas of
abscission,
hemorrhaging, atelectasis, acute emphysema.
The following complications are typical of influenza pneumonia:
• carnification;
• abscessing;
• purulent pleurisy;
• acute and chronic bronchiectasis;
• purulent mediastinitis;
• pneumofibrosis;
• chronic obstructive emphysema.
Due to generalized viremia, the following changes appear in internal organs:

• в the liver, kidneys, heart dystrophic changes in
the parenchymatous cells;
• full blood vessels;
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- Interstitial (interstitial) inflammation;

- glomerulonephritis;
- serous meningitis; influenza
- encephalitis;
- в ganglia sympathetic и parasympathetic parts
autonomic nervous system occur dystrophic
changes in neurons, small hemorrhages;
• thrombophlebitis, thrombarteritis.
► PARAGRIPT◄
Parainfluenza is an influenza-like infectious disease characterized

by predominantly upper respiratory tract involvement and
moderate intoxication.
ETHIOPATOGENESIS
The causative agent of parainfluenza is a pneumotropic RNA-
containing virus of types 1-4 of the family Paramyxoviridae. Parainfluenza
virus causes the formation of multinucleated cellular symplasts.
The pathogenesis of the disease is similar to that of influenza, but
intoxication is less pronounced and the course of the disease is mild,
resembling the course of a mild form of influenza.
Parainfluenza develops in the upper respiratory tract
catarrhal laryngotracheobronchitis.
Proliferation of bronchial epithelium with the formation of

pillow-shaped outgrowths of epithelium, accompanied by
dystrophic changes in the epithelium, vascular hemorrhage and
focal lymphohistiocytic infiltration of the stroma. Exudate in
bronchi and lumen of alveoli is serous or serous-mucous. In
interalveolar septae
- interstitial (interstitial) inflammation, but its degree is less
pronounced than in influenza.
Complications of parainfluenza are due to the accession of secondary
infection, which determines the nature of the resulting changes.
Parainfluenza virus is often accompanied by laryngeal edema due to acute
laryngitis complicated by false croup.
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► RESPIRATORY SYNCYTIAL INFECTION◄
Respiratory syncytial infection (PC infection) is an acute

respiratory disease caused by a virus with moderate
contagiousness.
ETHIOPATHOGENESIS
PC virus belongs to RNA-containing viruses, family
Paramyxoviridae, and has the ability to form giant cells and syncytium in
tissue culture.
The pathogenesis of the disease is similar to that of influenza and
parainfluenza infection. Small bronchi and lungs are affected first, followed
by the upper respiratory tract. Generalization of infection is possible, which
is especially characteristic of children of the first months of life.
For PC infection characterized development
catarrhal laryngotracheobronchitis, bronchiolitis
и small-focal
bronchopneumonia.
Proliferation of the epithelium of small bronchi in the form

of papillae or bulges consisting of large cells with light-colored
large nuclei of rounded shape. The cytoplasm of such cells
contains small RNA-rich inclusions (viruses). Exudate in the
alveoli is represented mainly by serous fluid with macrophages,
occasionally there are giant cells, a small number of
neutrophilic leukocytes.
In interalveolar septa there is cellular
infiltration represented by lymphoid and histiocytic cells.
elements. In connection with bronchiolitis, areas of atelectasis
and acute emphysema are noted in the lungs.
When the infection generalizes to the internal organs, characteristic

changes occur: in the intestine, kidneys, pancreas and liver, there is papillary
overgrowth of epithelium. In the brain, the changes are very similar to those
in parainfluenza.
► ADENOVIRUS INFECTION◄
Adenovirus infection is an acute respiratory disease

characterized by lesions of the upper respiratory tract,
conjunctiva, lymphoid tissue of the pharynx and pharynx.
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ETIOMATOHEHE3
The causative agent of the disease belongs to DNA viruses of the
Adenoviridae family. The source of infection is a sick person and carriers.
Pneumotropic virus is adsorbed on epithelial cells of the upper respiratory
tract and penetrates through pinocytosis, then transported to the nucleus,
where it reproduces. Virus exit from the nucleus leads to cell death and
development of viremia, which determines general intoxication.
MATOQOOGI1ESQA ANATOMY
The nature of changes in adenovirus infection depends on the severity
of the course.
EASY FORM
Characterized by acute catarrhal
rhinolaryngotracheobronchitis and acute catarrhal pharyngitis.
Acute catarrhal
conjunctivitis.
In regional lymph nodes - hyperplasia of lymphoid tissue. In

the epithelium of the upper respiratory tract - irregular staining
and enlargement of nuclei due to accumulation of DNA in
them, fuchsinophilic inclusions. Similar changes in alveocytes.
In the mucous membrane of the upper respiratory tract also
takes place
full blood vessels, small hemorrhages, focal lymphohistiocytic
infiltration.
HARD FORM
In addition to the respiratory system, intestinal epithelium, liver
cells, epithelium of pancreatic ducts, epithelium of renal
tubules are affected. In parenchymatous organs - dystrophy and
interstitial (interstitial)
inflammation; meningoencephalitis.
Accession of secondary infection changes the nature of
morphologic changes in organs,
with suppuration and necrosis.
Complications are caused by secondary infection. These are mainly
sinusitis, otitis media, sore throats, pneumonia, etc.
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INFECTIOUS DISEASES OF CHILDHOOD
Among pediatric airborne infections, measles is of particular

importance, while diphtheria, scarlet fever and meningococcal infections
are common among bacterial infections in children.
► CORE
Measles is an acute, highly contagious disease characterized by

catarrhal inflammation of the mucous membranes of the upper
respiratory tract, conjunctiva and a patchy papular rash on the
skin.
ETHIOCOGIA.
The causative agent of measles is an RNA-containing virus of the
Paramyxoviridae family. It has a complex antigenic structure and has
infectious, complement-binding, hemagglutinating and hemolysing
properties. Measles virus is unstable in the external environment, sensitive to
ultraviolet rays and visible light. Only children up to 3-6 months of age who
have received antibodies against measles virus from their mother have
temporary natural protection. If the mother has not had the disease and is not
immunized, the child is susceptible to measles from the first days of life.
MAATOGEHE3
The route of transmission is airborne. The mucous membranes of the
upper respiratory tract and, less frequently, the conjunctiva are the entry
points of infection.
The virus replicates in epithelial cells and then penetrates into lymph
nodes. From day 2-3 of the incubation period, the virus is detected in the
blood (primary viremia). The epithelium of the respiratory tract, conjunctiva,
salivary glands and organs of the immune system are most intensively
affected in the outcome of viremia. A week after the onset of the disease,
secondary viremia develops, which is accompanied by intoxication,
increased body temperature, catarrhal phenomena. On the 4th-5th day after
the appearance of catarrhal symptoms, a measles rash appears. The
appearance of the rash corresponds to the development of an active immune
response in the body, which involves NK-cells, cytotoxic T-lymphocytes and
plasma cells producing antibodies. By the time of the immune response, the
measles patient develops anergy with a decrease in hypersensitivity
reactions, lymphocyte proliferation and lymphokine secretion.
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Enanthema - on the mucous membranes of cheeks, lips, gums,
less often conjunctiva - small whitish dots surrounded by a
corolla of hyperemia. The most typical localization of
enanthema is in the area of the transitional fold at the small
molars (Filatov-Koplik spots).
Exanthema is a rash on the skin. The rash is usually patchy and

papular, first appearing behind the ears, then on the face, neck
and extending to the trunk and extremities.
In severe course - panbronchitis, small focal and confluent

pneumonia with necrotic character. Lung on section - walls of
small bronchi and bronchioles are sharply distinguished by
their white color and dry appearance
("measles pseudocaseous pneumonia").
Microscopically, measles is characterized by the formation of

two types of giant cells:
• Wartin-Finkeldey giant cells - formed in areas of
lymphocyte aggregation, they may contain up to 50-100
nuclei and small oxyphilic inclusions in the nuclei and
cytoplasm;
• epithelial giant cells - formed from type II pneumocytes,
epithelium of the upper respiratory tract, salivary glands,
and other epithelial tissues.
Microscopically, enanthema foci are full-bloodedness, edema,
lymphohistiocytic infiltration, vacuolization and necrosis of
epithelium with its subsequent sloughing, formation of
epithelial giant cells, which can be detected in smears from the
oral mucosa. Microscopically in areas of exanthema - full
blood vessels, para- and dyskeratosis of epithelium,
vacuolization of epithelial cells. Formation of giant cells is
typical. In the dermis - full blood vessels, weak
lymphohistiocytic infiltration. In the future, pigmentation due
to erythrocyte diapedesis and hemosiderin formation persists
for a long time at the site of the rash.
Bronchi, lungs - signs of bronchitis, bronchiolitis and
pneumonia. The epithelium shows signs of
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squamous cell metaplasia и formation giant

epithelial cells. Characterized by lesion
peribronchial tissue and lung interstitium.
Complications of measles can be primary, i.e., caused directly by the
measles virus, and secondary, caused by another, mainly bacterial infection.
Secondary complications may develop within a few months of the disease.
Complications can arise from a wide variety of organs and systems:
• respiratory systems (pneumonias, laryngotracheobronchitis,

croup);
• digestive system (stomatitis, enteritis, colitis);
• of the nervous system (meningitis, encephalitis);
• eyes (conjunctivitis, blepharitis, keratitis);
• skin (pyoderma, phlegmons);
• excretory system (cystitis, pyelonephritis).
► DIFTERIA◄
Diphtheria is an acute infectious disease characterized

predominantly by fibrinous inflammation in the foci of fixation of
the causative agent and general intoxication.
ETHIOLOGY
The source of infection is a sick person or a bacterial carrier. Diphtheria
is a typical anthroponosis. The disease is caused by toxinogenic, i.e. exotoxin-
producing, strains of Corypobacterium diphteriae. People without antitoxic
immunity (unvaccinated children and adults whose postvaccine immunity has
expired) become ill. The source of infection is sick people and bacillus
carriers. The route of transmission is airborne; contact route is also possible,
as the pathogen persists in the external environment for a long time when
dried. Entrance gate - the mucous membrane of the upper respiratory tract,
less often - damaged skin. The incubation period is 2-10 days. Diphtheria
bacterium multiplies in the area of the entrance gate (does not penetrate into
the blood), releasing exotoxin, which is associated with both local and general
changes.
292
PATHOGENESIS.
The scheme of diphtheria pathogenesis is presented in Fig. 47.
Figure 47. Scheme of pathogenesis of diphtheria.
Due to the peculiarities of diphtheria, local and general changes are
distinguished.
Local changes
Local changes are localized in the mucous membrane of the pharynx
(pharyngeal diphtheria 80%), larynx, trachea and bronchi (20%). Diphtheria of
the nose, eye, skin, genitals, and wound surfaces is very rare.
ZEVA DIFTERIA
Locally on necrotized mucous membrane of tonsils dense
yellowish-white films, about 1 mm thick, are formed. In
adjacent areas, the mucous membrane is full bloody, with small
hemorrhages. The soft tissues of the neck are e d e m a t o u s ,
sometimes the edema spreads
on the anterior chest wall.
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Inflammation has the character of diphtheritic: deep necrosis of

tonsil tissue and the presence of squamous epithelium lining
the mucous membrane. The film does not peel off for a long
time, which creates conditions for the absorption of exotoxin
produced by diphtheria bacteria,
which causes severe general intoxication of the patient's body.
UPPER RESPIRATORY DIPHTHERIA

It is characterized by pronounced local changes in the larynx,
trachea and large bronchi and slight general intoxication. The
mucous membrane develops
croup inflammation.
The resulting film is easily detached because the cylindrical

epithelium is loosely connected to the underlying tissue and
necrosis is superficial. The detached films may obstruct the
airway lumen, resulting in true croup.
The spread of the process to the small bronchi leads to
descending croup and focal pneumonias.
General changes
General changes are most pronounced in the cardiovascular system,
peripheral nervous system, adrenal glands, and kidneys.
• toxic myocarditis: cardiomyocytes show fatty dystrophy and foci of
myolysis, stroma shows edema, vascular hemorrhage, sometimes
infiltration with lymphoid and histiocytic cells. As a result of
myocarditis, diffuse small focal cardiosclerosis develops, which may
be the cause of cardiovascular insufficiency in recurrent patients;
• fibrin thrombi develop in small vessels due to the coagulopathic action
of exotoxin;
• in the nervous system - diphtheria polyneuropathy - neuritis with
disintegration of myelin of axial cylinders; in ganglia - dystrophic
changes of cells up to necrosis. All these changes reach a maximum
after 1.5-2 months and cause late paralysis;
• adrenal glands - dystrophy and necrosis of cells in the brain and
cortical substance, small hemorrhages in the stroma;
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• kidneys - necrotic nephrosis с formation acute

renal failure;
• lymph nodes, spleen, bone marrow - hyperplasia of lymphoid tissue.
• infectious-toxic myocarditis;
• diphtheria polyneuropathy;
• acute adrenal insufficiency;
• cerebral edema;
• infectious-toxic shock;
• complications of true croup:
- asphyxiation;
-aspiration pneumonia;
-Complications of tracheostomy and tracheal intubation.
► SCARLATINA.
Scarlatina is an acute infectious disease characterized by

symptoms of general intoxication, sore throat and skin rashes. The
causative agent of scarlatina is group A β-hemolytic
streptococcus.
ETHIOPATOGENESIS
The causative agent of scarlatina is a hemolytic streptococcus of group
А. The source of infection - patient any with any form
of streptococcal infection.The main route of transmission is
airborne. The entrygateway infections most often is most often
the mucous membrane of tonsils, pharynx, rarely the surface of wounds or
burns. The incubation period is from 1 to 12 days, more often 2-7 days. The
pathogen, once on the mucous membrane of the pharynx, multiplies,
producing endotoxin. All subsequent local and general changes are due to the
developing toxicosis. The mucous membrane of the pharynx becomes
inflammation, and there's an inflammation regional
lymphadenitis.
Primary scarlatinoid affect and primary scarlatinoid complex are formed.
Circulation of endotoxin and streptococcus in the blood determines the
appearance of antibodies and general changes: exanthema, fever,
intoxication. Up to the 2nd week of the disease (first period) there is
sensitization of the organism to streptococcus and, starting from the 2-3rd
week,
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the infectious-allergic period (second period) develops. Allergic reactions are

presented in the joints, blood vessels, heart and skin.
CLASSIFICATION
1. By type:
• typical form (pronounced signs of typical localization of the primary
affect + rash);
• atypical forms:
-sterile forms (scarlatina without rash);
- с aggravated symptoms (hypertoxic
and hemorrhagic);
-extrabuccal form;
2. In terms of severity:
• light;
• of medium severity;
• heavy:
- toxic;
- septic;
- toxic-septic;
3. Downstream:
• without allergy waves;
• with allergy waves;
• with complications:
-allergic type (nephritis, arthritis, synovitis, reactive
lymphadenitis);
-purulent (of a local nature);
-with septicopemia;
• abortive course.
Local changes
In the pharynx and tonsils - sharp hemorrhage, passing to the
mucous membrane of the mouth, tongue, pharynx - "flaming
pharynx", "crimson tongue". The tonsils are sharply enlarged,
red in color - catarrhal angina. Later, foci of necrosis appear in
the tonsil tissue, and necrotic sore throat characteristic of
scarlatina develops.
General changes
Are caused by marked intoxication, which is manifested
primarily by exanthema (rash). Rash
appears from the 2nd day of the disease, has a fine-pointed.
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character, bright red color, covers the entire surface.

of the body, except for the nasolabial triangle.
Local changes
Foci of coagulation necrosis in tonsils are surrounded by small
cellular reaction on the background of sharp full blood vessels,
hemorrhages. In severe course, necrosis spreads to the soft
palate, pharynx, auditory tube, middle ear, lymph nodes and
neck tissue. Rejection of necrotic masses is accompanied by
the formation of ulcers on the tonsils. In the cervical lymph
nodes there is a sharp hemorrhage, there are small foci of
necrosis and myeloid infiltration.
General changes
• skin - hemorrhage, edema, perivascular lymphohistiocytic
infiltrates.
In the superficial layers
of the epidermis - vacuolization of cells, parakeratosis
with subsequent necrosis. Later, the necrosis areas are
rejected, and there is a characteristic lamellar peeling of
the skin in the 2-3rd week of the disease;
• liver, kidneys, myocardium - protein and fatty
parenchymatous dystrophies, interstitial (interstitial)
inflammation;
• lymph nodes, spleen, lymphoid apparatus of the intestine
- hyperplasia of lymphoid tissue and myeloid metaplasia;
• the brain and the ganglia of the autonomic nervous
system.
system - circulatory disorders and dystrophic changes in
nerve cells.
Severe septic form of scarlatina - characterized by pronounced purulent-

necrotic changes in the pharynx with the development of pharyngeal abscess,
purulent otitis media, purulent osteomyelitis of the temporal bone, purulent
ethmoiditis, purulent-necrotic lymphadenitis, phlegmon (soft or hard) of the
neck. Phlegmon may in some cases lead to arrosion of large vessels in the
neck and fatal bleeding. The transition of purulent processes from the
temporal bone or paranasal sinuses causes the development of brain abscess
or purulent meningitis.
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Severe toxic form of scarlatina - manifested by severe general intoxication.

There is a sharp hyperemia in the pharynx, capturing even the esophagus,
hyperplasia of lymphoid tissue and dystrophy in various organs, a sharp
circulatory disorder.
Complications arise in severe forms of scarlatina due to the spread of
purulent-necrotic inflammation from the pharynx to the surrounding tissues:
pharyngeal abscess, phlegmon of the neck, purulent otitis media, purulent
sinusitis, purulent osteomyelitis of the temporal bone. Phlegmon of the neck
can lead to arrosion of the vessel and bleeding. Transition of the purulent
process from the temporal bone to the brain tissue can cause the
development of purulent meningitis or brain abscess.
► MENINGOCOCCAL INFECTION◄
Meningococcal infection is an acute infectious disease caused by

the pathogen Neisseria meningitidis and characterized by lesions
of the brain membranes with the development of meningitis,
meningoencephalitis, encephalomyelitis, as well as generalization
of infection with selective capillary endothelial damage and the
development of infectious toxic shock.
ETHIOPATOGENESIS
The causative agent of meningococcal infection is Neisseria
meningitidis serovars A, B, C - cocci that are extremely unstable in the
external environment. The source of infection is patients with generalized
meningococcal infection, carriers and patients with localized forms. The
greatest epidemic danger is posed by patients with generalized forms of
meningococcal infection. The route of transmission is airborne.
The entrance gate of infection is the nasopharyngeal mucosa. In most
cases, meningococcus on the nasopharyngeal mucosa does not cause local
inflammation. The path of spread of the pathogen in the body is
hematogenous. Bacteremia is accompanied by massive decay of
meningococci - toxemia.
In the pathogenesis of meningococcal infection, a combination of
septic and toxic processes with allergic reactions plays a role. Most lesions
(meningitis, otitis media, labyrinthitis, arthritis, pericarditis, uveitis and
others) of the early period of the disease are due to the primary-septic
process. Toxins,
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formed as a result of meningococcal death, lead to damage to the vessels of

the microcirculatory channel, in which plasmorrhages, fibrinoid necrosis of
the wall, fibrin thrombi develop. These processes eventually lead to severe
damage and functional disorders of vital organs, primarily the brain, kidneys,
adrenal glands, and liver.
Thus, two points can be distinguished in the pathogenesis of
meningococcal infection:
• lesions on the brain;
• capillary endothelial damage with the development of DIC and,
as its highest manifestation, infectious toxic shock (ITS).
CLASSIFICATION
• Localized forms:
-carrying meningococcus;
-meningococcal nasopharyngitis.
• Generalized forms:
- meningococcemia;
-purulent meningitis;
-purulent meningoencephalitis;
-combined form (meningitis with meningococcemia, etc.).
• Rare forms:
- arthritis;
- myocarditis;
- osteomyelitis;
-iridocyclitis, etc.
• In terms of severity:
-light form;
-moderately severe form;
-severe form;
-hypertoxic (lightning) form.
The incubation period (regardless of the form of the disease) ranges from 2 to
10 days.
Meningococcal nasopharyngitis.
Hyperemia и swelling posterior wall of the
pharynx, its granularity due to hyperplasia of lymphoid
follicles.
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Signs of catarrhal inflammation of the nasopharyngeal mucosa.
Meningococcal purulent meningitis.

Brain membranes on the 1st day of the disease are sharply full
blooded, saturated with slightly cloudy serous exudate. By 2-3
days, the exudate thickens, acquires a greenish-yellow color
and purulent character, located in the form of a yellowish-
greenish "cap" or "cap".
The vessels of the soft cerebral membranes are sharply full-

blooded, the subarachnoid space is dilated, saturated with
leukocytic exudate, permeated with fibrin threads. The process
from the vasculature can move to the
brain tissue with meningoencephalitis.
Meningococcemia is a variant of sepsis (septicemia or septicopemia) caused
by meningococcus. It is characterized by generalized damage to blood
vessels, joints, parenchymatous organs, adrenal glands and kidneys.
On the skin - characteristic hemorrhagic rash (hemorrhagic
purpura), multiple hemorrhages on mucous membranes and
serous membranes. Bilateral massive hemorrhages in the
adrenal glands with the development of acute adrenal
insufficiency (Waterhouse-Friederiksen syndrome), acute
cerebral edema,
symmetrical cortical necrosis of the kidneys.
В soft cerebral sheath. - signs serous

meningitis. In the adrenal glands, massive hemorrhages and
foci of necrosis. In the kidneys - necrotizing nephrosis.
Death of patients may occur from bacterial shock, the severity of which is
aggravated by hemorrhages in the adrenal glands (with the development of
acute adrenal insufficiency), less often there is acute renal failure.
A complication of purulent meningitis is hydrocephalus, which occurs when
exudate is organized and the medial and lateral foramen of the IV ventricle is
obliterated and fluid circulation is impeded. Patients die from cerebral
edema, displacement of the brain along the cerebral axis and wedging of the
cerebellar tonsils into the greater occipital foramen, resulting in respiratory
arrest.
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SECTION XIV.
TUBERCULOSIS, SEPSIS, HIV- INFECTION/SPD
► TUBERCULESIS◄
Tuberculosis is a chronic infectious disease that can affect all

human organs and tissues, but more often the pathological
process develops in the lungs.
ETHIOLOGY
The causative agent is acid-fast Mycobacterium tuberculosis
(Mycobacterium tuberculosis). The human and bovine types of
mycobacterium are pathogenic for humans. Mycobacterium is a facultative
anaerobe, but optimal conditions for growth are found at maximum oxygen
saturation, which determines the predominant lung damage.
Mycobacterium is characterized by pronounced variability: the
presence of branching, coccoid forms, λ-forms, which under the influence of
chemopreparations can lose their cell wall and persist in the body for a long
time.
PATHOGENESIS.
The pathogenesis of tuberculosis is characterized by the presence of
several features:
• penetration of mycobacterium occurs by aerogenic or alimentary route
and leads to infection, the emergence of latent tuberculosis focus,
determining the formation of infectious immunity;
• under conditions of sensitization of the organism, there is an outbreak
of the process with exudative tissue reaction and caseous necrosis. The
change of hyperergy leads to the appearance of productive tissue
reaction - formation of characteristic tuberculous granuloma and
sclerosis.
• The constant change of immunologic reactions (hyperergy →
immunity → hyperergy) is the basis of the wave-like chronic course of
tuberculosis with alternation of outbreaks and remissions.
CLASSIFICATION
Clinical and morphological peculiarities of the
disease are determined by the temporal factor of "separation" of the disease
from the period of infection.
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There are three main types of pathogenetic and clinical and morphologic
manifestations of tuberculosis:
• primary tuberculosis;
• Hematogenous tuberculosis (postprimary);
• secondary tuberculosis.
PRIMARY TUBERCULOSIS
The following are characteristic features of primary tuberculosis:
• develops during the period of infection;
• characteristic sensitization и allergy,
immediate hypersensitivity reactions (IHR);
• predominance of exudative-necrotic changes;
• tendency to hematogenous and lymphoglandular generalization;
• paraspecific reactions в in the form of vasculitis,
arthritis, serositis;
• predominantly affects children, but has recently been reported in
adolescents and adults;
• morphological manifestation is is a
primary tuberculosis complex.
The primary tuberculosis complex includes 3 major components:

• primary affect - focus of caseous pneumonia, rapidly changing to
caseous necrosis of white-yellow color of dense consistency; localized
subpleurally in the 3, 8, 9, 10 segments, more often of the right lung;
• Tuberculous lymphangitis - inflammation of lymphatic vessels;
• tuberculous lymphadenitis - inflammation of regional lymph nodes in
which caseous necrosis develops.
Variants of the course of primary tuberculosis:

• progression-free: characterized by attenuation of primary
tuberculosis and healing of foci of the primary complex;
The primary pulmonary affect is encapsulated, obesitized, and
undergoes ossification (Gon's focus is formed). At the site of
tuberculous lymphangitis due to fibrosis of tuberculous tubercle
tubercles, a fibrous m a s s appears. Affected lymphatics
the nodules petrify and ossify. A scar forms at the site of the
tuberculous ulcer in the intestine.
• with progression:
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- Hematogenous generalization - associated with the entry of

mycobacteria into the blood, manifested in two forms:
o miliary form - characterized by the appearance of multiple
miliary tuberculous tubercle tubercle tubercles in the organs;
o Large-focal form - larger foci are formed;
- lymphogenic generalization - manifested by involvement of new
groups of lymph nodes (not only regional ones) in the tuberculosis
process: in pulmonary complex - peritracheal, supra- and
subclavian, cervical, etc.; in intestinal complex - all groups of
mesenteric lymph nodes (tuberculous mesadenitis).
Bronchoadenitis shows clinical signs of tuberculosis, primarily
cough with large amounts of sputum;
- primary affect growth - the most severe form of progression,
characterized by caseous necrosis of the perifocal inflammation
zone. It may lead to the development of lobar caseous pneumonia
(transient pulmonary consumption), ending, as a rule, with the
death of the patient;
- mixed form of progression - most characteristic o f weakened
patients;
• Chronic course - possible in two situations:
- with healed primary affect in the lymph nodes, the process
progresses with the lesion of more and more groups; the disease
takes a chronic course with alternating outbreaks and remissions.
In the lymph nodes there is a combination of old changes -
petrificates with fresh caseous lymphadenitis;
- in the formation of a primary pulmonary cavern and the
development of primary pulmonary consumption.
HEMATOGENOUS TUBERCULOSIS
The following are characteristic features of hematogenous tuberculosis:
• occurs after primary tuberculosis in the presence of foci of
hematogenous dropout or not fully healed foci in the lymph nodes
against the background of expressed immunity to mycobacteria, but
hypersensitivity (sensitization to tuberculin);
• productive tissue reaction (granulomas) predominates;
• has a tendency to hematogenous generalization.
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There are 3 main forms of hematogenous tuberculosis:

• generalized hematogenous tuberculosis;
• hematogenous tuberculosis с predominantly with
predominantly pulmonary involvement;
• hematogenous tuberculosis с predominantly
extrapulmonary involvement.
Generalized hematogenous tuberculosis is the most severe form, with

uniform rash of tuberculous tuberculous tuberculous tubercles and foci in
many organs. This form of hematogenous tuberculosis, in turn, includes:
• acute tuberculosis sepsis - characterized by the spread of tiny foci of
necrosis in all organs, with the presence of a large number of
mycobacterium tuberculosis in these foci. The disease proceeds with
the phenomena of massive bacillemia and has the character of severe
sepsis;
• acute general miliary tuberculosis - characterized by the formation of
homogeneous miliary tubercles throughout the body; the structure of
the tubercles is of the type of specific tuberculous granuloma.
• acute general large-focal tuberculosis - usually occurs in weakened
patients and is characterized by the formation of large (up to 1 cm in
diameter) tuberculous foci in different organs;
• chronic generalized miliary tuberculosis.
Hematogenous tuberculosis with predominant lung involvement

• acute miliary;
• chronic miliary;
• chronic large-focal or
hematogenously disseminated:
-occurs only in adults;
-predominantly cortico-pleural localization;
-productive tissue response;
-development of reticular pneumosclerosis and pulmonary emphysema;
-presence of "stamped" caverns;
-hypertrophy of the right ventricle of the heart ("pulmonary heart");
-presence of extrapulmonary tuberculosis focus.
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Hematogenous tuberculosis with predominantly extrapulmonary involvement

• arises from hematogenous outbreaks of primary
tuberculosis;
• distinguish (basic forms):
-bone and joint tuberculosis;
-tuberculosis of the kidneys, genitals;
-tuberculosis of the skin;
• the following forms (phases) are distinguished:
-acute focal phase;
-acute destructive phase;
-chronic focal phase;
-chronic destructive phase;
• cause of death is, as a rule. is usually
failure of function of the affected organ.
SECONDARY TUBERCULOSIS
Key Features:
• develops in adults who have had a primary infection;
• selectively pulmonary localization of the process;
• predominant localization in the 1st and 2nd segments (apex of the
lung);
• contact and intracanalicular spread;
• change clinical and morphologic forms, which are
phases of the tuberculosis process (see below);
• is not characterized by caseous lymphadenitis;
• has a chronic course.
Forms of secondary tuberculosis:

• acute focal tuberculosis - represented by a focus (Abrikosov reinfect) -
a focus of caseous bronchopneumonia localized, as a rule, in the 1st or
2nd segments of the lung (more often in the right lung). Petrificates
(Aschoff-Pulev foci) occur during healing of Abrikosov's foci;
• fibrous focal tuberculosis - the source of exacerbation is Ashoff-Poole
foci, around which acinosis and lobular foci of caseous pneumonia
arise, which are further encapsulated and petrified;
• infiltrative tuberculosis - characterized by
the occurrence of Assmann-Redeker focus, which is characterized by a
significant prevalence of perifocal
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serous inflammation over a relatively small area of caseous necrosis;
Figure 48. Forms of secondary tuberculosis.
• tuberculoma - occurs when the focus of perifocal inflammation and

encapsulation of caseous necrosis (often taken radiologically as
peripheral lung cancer);
• Caseous pneumonia - develops during progression of infiltrative
tuberculosis; caseous changes prevail over perifocal changes;
• acute cavernous tuberculosis - occurs when a cavity (cavern) is
formed in the place of an infiltrate or a focus of caseous pneumonia.
The cavern has an oval or rounded shape, communicates with the
lumen of the segmental bronchus. The inner layer of the cavern is
represented by caseous masses;
• fibrous cavernous tuberculosis ("chronic pulmonary consumption") -
occurs when acute cavernous tuberculosis becomes chronic. The
cavernous wall is fibrous tissue on the outside and caseous masses and
a layer of granulations on the inside. The inner surface is uneven with
crossing cavity
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beams represented by obliterated vessels and bronchi. Bronchogenic

spread of the process leads to the appearance of acinar and lobular foci
of caseous pneumonia in the lower parts of the same lung, as well as
in the second lung (later);
• cirrhotic tuberculosis - a possible final outcome of fibrotic cavernous
tuberculosis, in which there is a massive overgrowth of connective
tissue with deformation of the lung (lung cirrhosis).
• In primary tuberculosis there is pleurisy (with a large number of
lymphocytes in the exudate), leptomeningitis.
• Sequestrations, deformities, abscesses and fistulas are seen in bone
tuberculosis.
• In secondary tuberculosis, complications are more often related to the
cavernous cavity - hemorrhage, pneumothorax, and pleural empyema
(when the cavernous cavity bursts into the pleural cavity).
• Secondary tuberculosis may result in renal amyloidosis and death
from chronic renal failure.
• The chronic course of tuberculosis is usually accompanied by the
development of pulmonary heart and pulmonary-cardiac failure.
► CEPSIS◄
Sepsis is an acyclic infectious disease caused by various

microorganisms and characterized by extremely altered body
reactivity.
Sepsis is an expression of an inadequate (more often hyperergic)

reaction to an infectious agent (Abrikosov-Davydovsky reactologic theory).
Sepsis differs from other infections in etiologic, epidemiologic, clinical,
immunologic and pathologic features:
• Sepsis is a polyethiologic disease; the most frequent causative agents
are staphylococci, meningococci, Klebsiella, pseudomonas, and
Escherichia coli; can be caused by fungi;
• not contagious, not reproducible in experimentation;
• immunity doesn't develop;
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• proceeds acyclically, clinical manifestations are nonspecific,

independent of the causative agent;
• morphologic changes are nonspecific.
CLASSIFICATION
1. Depending on the etiologic factor:
• bacterial - the most most common,
staphylococcal and pseudomonas sepsis;
• fungal;
2.Depending on the nature of the entrance gate:
• surgical;
• Therapeutic (para-infectious);
• wound;
• Umbilical (most common);
• uterine;
• otogenic;
• odontogenic,
• tonsillogenic;
• urological;
• Cryptogenic (entry gate unknown);
• "iatrogenic" sepsis - the infection is introduced during intubation (the
entrance gate is the lungs), catheter insertion (catheterization sepsis),
vascular shunts ("shunt sepsis") and other medical manipulations;
3. Depending on the clinical and morphologic features:
• septicemia;
• septicopoiesis;
• septic (bacterial) endocarditis;
• chroniosepsis.
In sepsis, local and general changes are noted.

Local changes develop in the focus of infectious agent introduction
(entrance gate) or away from it (less often) and are represented by a septic
focus.
A septic focus is a focus of purulent inflammation in conjunction with
lymphangitis, lymphothrombosis, and lymphadenitis, which result from the
spread of infection through the lymphatic system, and phlebitis and
thrombophlebitis, which develop due to the spread of infection through the
circulatory system.
The overall changes are as presented:
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• dystrophy and interstitial inflammation of parenchymatous organs

(hepatitis, nephritis, myocarditis), as well as vasculitis;
• hyperplasia of lymphoid and hematopoietic tissue with the
development of generalized lymphadenopathy (enlargement of lymph
nodes), septic spleen (sharply enlarged flabby spleen with abundant
pulp scraping) and leukocytosis (up to the development of leukemoid
reaction).
SEPTICEMIA
Septicemia is characterized by the following features:

• characteristically rapid (a few days), sometimes
lightning-like course;
• occurs with a distinct hyperergic reaction;
• the septic focus may not be pronounced;
• General changes prevail - dystrophy and inflammation of
parenchymatous organs, vasculitis, hyperplasia of lymphoid and
hematopoietic tissue;
In addition, they identify:
• Jaundice of the skin and sclerae (associated with hemolysis under the
influence of bacterial toxins);
• Hemorrhagic skin rash due to vasculitis or associated with the
frequently associated disseminated intravascular coagulation
syndrome (DIC);
• possible development of septic (toxic-infectious) shock, which is more
often endotoxic (caused by lipopolysaccharides of Gram-negative
microorganisms), less often - exotoxic (in Gram-positive infections);
• A frequent complication of septic shock is DIC, which can lead to
adrenal hemorrhage with the development of acute adrenal
insufficiency (Waterhouse-Friederiksen syndrome).
SEPTICOPIEMIA
Septicopiemia is characterized by the following features:

• hyperthermia is not pronounced;
• disease runs more for a longer period of time, в
for several weeks;
• there are focal points of purulent inflammation in many organs -
abscesses, due to bacterial embolism. The first abscesses
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are formed, as a rule, in the lungs (primary abscesses), later they occur
in other organs - liver, kidneys (embolic purulent nephritis), bone
marrow (purulent osteomyelitis), synovial membranes (purulent
arthritis), on the heart valves, more often tricuspid (acute septic
polyposis-ulcer endocarditis), in the membranes and brain tissue
(purulent leptomeningitis, brain abscess) and others.
• Complications are usually associated with the breakthrough of
pustules in the adjacent organs and tissues with the development of
empyema of the pleura, peritonitis, phlegmon, etc.
SEPTIC BACTERIAL ENDOCARDITIS
General Characteristics:
• The most frequent pathogens are white and golden staphylococcus,
green streptococcus, enterococci and others.
• the septic focus is localized on the heart valves;
• hypersensitivity reactions associated with the formation of circulating
toxic immune complexes are pronounced.
CLASSIFICATION
• By the nature of the flow:
- Acute endocarditis - duration about 2 weeks;
- subacute endocarditis - duration about 3 months;
- Chronic endocarditis - duration of several months (sometimes
several years).
• Depending on the presence or absence of background disease:
- Primary septic endocarditis (Chernogubov's disease): develops on
unchanged valves, accounts for 20-30% of endocarditis cases;
- Secondary septic endocarditis: develops against the background of
heart defects (more often rheumatic, less often - atherosclerotic,
syphilitic and congenital), a special form is endocarditis on
prosthetic valves.
Local changes (septic focus) are represented by polyposis- ulcerative
endocarditis; aortic valves or aortic and mitral valves are more often affected
simultaneously; in drug addicts often
310
the tricuspid valve is involved.

Extensive foci of necrosis and ulceration, often with
detachment of flaps and formation of holes (fenestra); massive
thrombotic deposits in the form of polyps in the areas of
ulceration; in secondary endocarditis, the above changes
develop against the background of malformation - sclerosis,
hyalinosis, calcification of valve flaps; myocardial hypertrophy
is noted.
Lymphocytic-macrophage infiltration (in acute endocarditis

with admixture of polymorphonuclear leukocytes); colonies of
microorganisms; massive precipitation of calcium salts in
thrombotic masses
(characteristic of subacute endocarditis).
General changes:
• Septic spleen (enlarged in size, with a tense capsule, gives abundant
scraping, often found in it infarcts, in subacute and chronic
endocarditis thickened due to sclerosis);
• changes associated with circulating toxic immune complexes:
- Generalized alterative-productive vasculitis (in microcirculatory
vessels) with development of multiple petechial hemorrhages on
the skin, mucous and serous membranes, conjunctiva
(hemorrhages on the conjunctiva of the lower eyelid at the inner
edge (Lukin-Libman spots) - a diagnostic sign;
- immunocomplex diffuse glomerulonephritis;
- arthritis.
• thromboembolic complications due to massive thrombotic deposits on
the valves with the development of infarcts and gangrene. More often
infarcts occur in the spleen, kidneys, brain. In case of multiple infarcts
we speak about thromboembolic syndrome.
CHRONIOSEPSIS
General Features:
• a long perennial course;
• decreased body reactivity;
• presence of a long-term non-healing septic focus (dental caries,
chronic tonsillitis, suppurative wounds);
311
• chronic intoxication leading to exhaustion (purulent resorptive fever)

and brown atrophy of organs (heart, liver, skeletal muscles);
• The spleen is usually small, flabby, and brown on section due to
hemosiderosis;
• amyloidosis (AA-amyloidosis) may develop.
► HIV INFECTION, ACQUIRED

IMMUNODEFICIENCY SYNDROME (AIDS)◄
HIV infection is a chronic progressive human disease caused by

a retrovirus that affects the immune system and creates an
immunodeficiency state, leading to the development of
opportunistic and secondary infections, as well as malignant
tumors.
HIV infection causes in the human body the emergence of chronic,

less often acute disease with predominant damage to blood cells and organs
of immunogenesis, the final stage of which is the total suppression of the
immune system and the development of acquired immunodeficiency
syndrome (AIDS).
ETHIOPATHOGENESIS
The causative agent is the T-lymphocytic (lymphotropic) human
immunodeficiency virus - HIV (NTLV-III or HIV) from the family of T-
lymphotropic retroviruses. Currently, 2 strains of human immunodeficiency
virus are known: HIV-1 and HIV-2.
The source of infection is an HIV-infected person, both at the stage of
asymptomatic carriage and in advanced clinical manifestations of the
disease. The greatest amount of the virus is found in blood, semen,
cerebrospinal fluid, breast milk, vaginal and cervical secretions.
Pathways of HIV transmission:
• Contact-sex transmission - characterized by the penetration of the
virus into the body through damaged skin and mucous membranes;
• sexual transmission - through sexual contact (hetero- and homosexual)
and associated with microtraumas of mucous membranes;
• parenteral route of transmission - characterized by ingestion of
312
virus directly into the bloodstream and occurs during

hemotransfusions of contaminated blood or its components, injections
using contaminated instruments, especially during drug
administration, organ and tissue transplants of donors;
• infection of the child most often occurs transplacentally during
pregnancy or during labor. High concentrations of the virus in the
mother's blood or AIDS, prematurity, natural childbirth and exposure
of the baby to the mother's blood increase the risk of HIV
transmission. Infection of the child can also occur through
breastfeeding by an HIV-infected mother, as well as through decanted
breast milk.
Parasitizing in helper T-lymphocytes (CD4+), the virus can remain
latent for a long time. An outbreak of viral replication can be triggered by
any infection, which accelerates the course of the infection. The RNA of the
virus, with the help of the reverse transcriptase enzyme, is incorporated into
the DNA of the cell, with subsequent synthesis of new viral particles,
resulting in the death of T lymphocytes. Infected monocytes, unlike
lymphocytes, do not die, but serve as a reservoir of latent infection.
In HIV infection, the ratio of T-helper and T-suppressors is disturbed
in the body. The damage of T-helpers leads to a decrease in the activity of
macrophages and natural killer cells, decreased production of antibodies by
B-lymphocytes, resulting in a marked weakening of the immune response.
CLASSIFICATION
There are 5 stages of HIV infection:
• incubation period - is 2-8 weeks. There are no clinical manifestations,
but an HIV-infected person can be a source of infection;
• primary-manifest (acute) period - in 50% of patients the disease
begins with nonspecific clinical manifestations: fever, myalgias and
arthralgias, lymphoadenopathies, nausea, vomiting, diarrhea, skin
rashes, etc. In some patients, this period of the disease is
asymptomatic;
• latent period - the latent period lasts several years (from 1 to 8-10
years). Clinical manifestations are absent, immune status does not
change, but the person is a source of infection (viral carriage is noted).
At the end of the latent period, generalized lymphadenopathy
develops;
• AIDS (secondary disease stage) - AIDS is characterized by the
development of bacterial, fungal, viral, protozoal, and
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parasitic diseases, tumor processes (more often lymphomas and

Kaposi's sarcoma). The main clinical manifestations of AIDS are
fever, night sweats, rapid fatigue, weight loss (up to cachexia),
diarrhea, generalized lymphadenopathy, hepatosplenomegaly,
pneumocystis pneumonia, progressive neurological disorders, internal
organ candidiasis, lymphomas, Kaposi's sarcoma, opportunistic and
secondary infections;
• terminal stage - cachexia, general intoxication, dementia, progressive
intercurrent diseases. The process ends with a fatal outcome.
Another classification distinguishes:

• incubation period;
• period of persistent generalized lymphoadenopathy;
• pre-AIDS or AIDS-associated complex;
• AIDS.
The main ones are lymph node changes, characteristic CNS lesions
and changes typical of opportunistic infections and tumors:
• follicular hyperplasia of lymph nodes followed by complete depletion
of lymphoid tissue. Lymph nodes are sharply reduced, determined with
difficulty;
• CNS lesion - HIV encephalomyelitis with major changes in the white
matter and subcortical nuclei of the brain. Microscopic examination
reveals microglial nodules, multinucleated symplasts, in which HIV
particles can be detected. Foci of softening and vacuolization of white
matter are detected in the lateral and posterior columns of the spinal
cord;
• opportunistic infections in AIDS - characterized by a severe recurrent
course, often with generalization of the process and resistance to
therapy. According to etiology, they are distinguished:
- infections caused by protozoa (pneumocysts, toxoplasmas,
cryptosporidium);
- fungal infections (genus Candida, cryptococcus);
- viral infections (cytomegaloviruses, herpetic viruses, some slow
infections viruses);
- bacterial infections (Mycobacterium avium intracellulare,
Legionella, Salmonella);
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• malignant tumors in AIDS occur in 40% of cases. The most

characteristic are Kaposi's sarcoma (in 30% of patients) and malignant
lymphomas (in particular, Burkitt's lymphoma).
Causes of death may include Kaposi's sarcoma, lymphomas,

infections caused by opportunistic flora (e.g., pneumocystis, mycoplasma,
cytomegalovirus pneumonia), as well as HIV encephalitis, and fungal
meningitis.
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CONTENTS.
CARDIOVASCULAR DISEASES.................................................................4
ATHEROSCLEROSIS ............................................................................4
HYPERTENSION .................................................................................10
CORONARY HEART DISEASE.........................................................15
CARDIOMIOPATHY...........................................................................20
CEREBROVASCULAR DISEASES ....................................................21
RHEUMATIC DISEASES...........................................................................23
REVMATISM .......................................................................................24
SYSTEMIC LUPUS ERYTHEMATOSUS..........................................35
RHEUMATOID ARTHRITIS ..............................................................40
SYSTEMIC SCLERODERMA.............................................................41
OTHER SYSTEMIC CONNECTIVE TISSUE DISEASES ................43
RESPIRATORY DISEASES........................................................................45
ACUTE BRONCHITIS.........................................................................45
BRONCHIOLITIS.................................................................................47
PNEUMONIA .......................................................................................48
LUNG ABSCESS..................................................................................58
LUNG GANGRENE .............................................................................60
CHRONIC BRONCHITIS ....................................................................63
BRONCHOECTASES ..........................................................................67
PULMONARY EMPHYSEMA............................................................69
BRONCHIAL ASTHMA ......................................................................73
INTERSTITIAL LUNG DISEASES ....................................................75
LUNG CANCER...................................................................................76
GASTROINTESTINAL DISEASES............................................................80
PHARYNGEAL AND PHARYNGEAL DISEASES ................................80
TONSILLITIS ...............................................................................80
ESOPHAGEAL DISEASES....................................................................83
ESOPHAGEAL DIVERTICULA .................................................83
EZOFAGIT....................................................................................84
GASTROINTESTINAL CANCER...............................................87
STOMACH DISEASES ..........................................................................89
GASTRITIS...................................................................................89
PEPTIC ULCER ...........................................................................94
STOMACH CANCER ..................................................................97
INTESTINAL DISEASES .......................................................................99
APPENDICITIS ............................................................................99
NONSPECIFIC ULCERATIVE COLITIS.................................102
CROWN'S DISEASE..................................................................104
COLORECTAL CANCER..........................................................107
316
DISEASES OF THE LIVER, GALLBLADDER AND PANCREAS.......108

LIVER DISEASES................................................................................108
HEPATOSES ..............................................................................109
HEPATITES................................................................................112
CYRROSIS OF THE HEAD ......................................................117
CANCER OF THE LIVER .........................................................120
DISEASES OF THE BILIARY TRACT AND GALLBLADDER...........121
CHOLECISTITIS........................................................................121
CHOLELITHIASIS.....................................................................124
DISEASES OF THE EXOCRINE PART OF THE PANCREAS ..........125
PANCREATITIS.........................................................................125
PANCREATIC CANCER...........................................................128
KIDNEY DISEASES ..................................................................................130
GLOMERULONEPHRITIS................................................................130
ACUTE RENAL FAILURE (ARF) ....................................................141
PIELONEFRITIS ................................................................................143
CHRONIC RENAL FAILURE (CRF)................................................147
UROLITHIASIS..................................................................................150
DISEASES WITH PREDOMINANT ENDOCRINE SYSTEM
INVOLVEMENT........................................................................................152
DISEASES WITH PREDOMINANT LESIONS OF THE PITUITARY
GLAND AND HYPOTHALAMUS .......................................................152
HYPOPITUITARISM .................................................................152
HYPERPITUITARISM...............................................................155
NON-SUGAR DIABETES .........................................................158
ADRENAL DISEASES .........................................................................160
ACUTE ADRENAL INSUFFICIENCY (ACUTE
HYPOCORTICISM)...................................................................161
PRIMARY CHRONIC ADRENAL CORTEX INSUFFICIENCY
(ADDISON'S DISEASE) ............................................................162
ADRENAL CORTEX HYPERFUNCTION...............................164
DISEASES INVOLVING THE THYROID GLAND 165 THYROIDITIS
.....................................................................................................165
STRUMA (ZOB).........................................................................169
HYPOTHYREOSIS ....................................................................173
THYROID TUMORS .................................................................175
DISEASES AFFECTING THE PARATHYROID GLANDS
. ............................................................................................................179
HYPERPARATHYROIDISM.....................................................179
HYPOPARATIREOSIS ..............................................................180
DISEASES WITH LESIONS OF THE INSULAR APPARATUS OF THE
PANCREAS..........................................................................................180
DIABETES MELLITUS .............................................................180
317
TUMORS OF THE ENDOCRINE PART OF THE PANCREAS

.....................................................................................................183
DISEASES OF THE MAMMARY GLANDS, FEMALE AND MALE
GENITAL SYSTEM ...................................................................................185
BREAST DISEASES ............................................................................185
MASTIT ......................................................................................185
MILK DUCT ECTASIA .............................................................186
FAT NECROSIS OF THE BREAST..........................................187
CYSTIC FIBROSIS OF THE BREAST (DYSHORMONAL) ..188
BREAST FIBROADENOMA ....................................................190
INTRADUCTAL PAPILLOMA OF THE BREAST .................191
BREAST CANCER ....................................................................191
CERVICAL DISEASES ........................................................................195
CERVICIT...................................................................................195
CERVICAL PSEUDOEROSION (ENDOCERVICOSIS) .........196
CERVICAL CANCER ................................................................198
UTERINE AND ENDOMETRIAL DISEASES .....................................200
INFLAMMATORY DISEASES. ENDOMETRITIS .................200
DYSFUNCTIONAL UTERINE BLEEDING
.....................................................................................................202
ENDOMETRIAL HYPERPLASIA ............................................202
ENDOMETRIOSIS .....................................................................204
UTERINE BODY TUMORS ......................................................206
OVARIAN DISEASES ..........................................................................208
NON-TUMOR OVARIAN CYSTS............................................208
OVARIAN TUMORS .................................................................211
MALE GENITAL DISEASES ...............................................................214
PROSTATITIS ............................................................................215
BENIGN PROSTATIC HYPERPLASIA...................................216
PROSTATE CANCER ...............................................................217
PREGNANCY PATHOLOGY. POSTPARTUM PATHOLOGY ..............219
ECTOPIC PREGNANCY ...................................................................219
TROPHOBLASTIC DISEASE ...........................................................222
HESTOSES .........................................................................................224
POSTPARTUM PATHOLOGY .........................................................229
PRENATAL PATHOLOGY .......................................................................232
GAMETOPATHIES............................................................................233
BLASTOPATHY ................................................................................235
EMBRIOPATHIES .............................................................................236
PHETOPATHY ...................................................................................243
PERINATAL PATHOLOGY......................................................................247
PREMATURITY AND PREMATURITY..........................................248
INFECTIOUS PERINATAL PATHOLOGY .....................................250
318
FETAL AND NEONATAL ASPHYXIA ...........................................252

NEONATAL PNEUMOPATHIES .....................................................253
BIRTH TRAUMAS.............................................................................255
HEMOLYTIC DISEASE OF THE NEWBORN ................................257
INTESTINAL INFECTIONS ....................................................................260
BREAST TIFF.....................................................................................260
DESENTERIA.....................................................................................265
AMEBIAZ...........................................................................................270
HOLERA.............................................................................................272
SALMONELLOSES ...........................................................................277
AIRBORNE INFECTIONS .......................................................................280
GRIPP..................................................................................................281
PARAGRIPT .......................................................................................285
RESPIRATORY SYNCYTIAL INFECTION.....................................286
ADENOVIRUS INFECTION .............................................................286
BARK ..................................................................................................288
DIFTERIA ...........................................................................................290
SCARLATINA....................................................................................293
MENINGOCOCCAL INFECTION ....................................................296
TUBERCULOSIS, SEPSIS, HIV/AIDS....................................................299
TUBERCULESIS ................................................................................299
CEPSIS ................................................................................................305
HIV INFECTION, ACQUIRED IMMUNODEFICIENCY
SYNDROME (AIDS)..........................................................................310
CONTENTS. ...............................................................................................314

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Systemic Patan

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MINISTRY OF EDUCATION AND SCIENCE OF THE RUSSIAN

S.I. Georgievsky Medical Academy

Federal State Autonomous Educational Institution of Higher

SHORT COURSE IN PATHOMORPHOLOGY

educational and methodological manual for students of higher educational

Kubyshkin Anatoly Vladimirovich, Professor, Doctor of Medical Sciences, Head of

Antonina Budnik, Candidate of Medical Sciences, Associate Professor, Department

The textbook on pathological anatomy was prepared at the Department of

The textbook is recommended for publication and assignment of the Academic

DEDICATED TO THE TEACHER

DOCTOR OF MEDICAL SCIENCES, PROFESSOR

Atherosclerosis (from Greek athere - porridge and sklerosis -

• The appearance of lipid spots and streaks;

Figure 1. Scheme of pathogenesis of atherosclerosis.

PATHOLOGIC ANATOMY AND MORPHOGENESIS

- accumulation of acidic glycosaminoglycans in the intima,

The lipoidosis stage is characterized by focal infiltration of the intima by

Lipids accumulate in smooth muscle cells and macrophages,

Proliferation of fibroblasts, the growth of which stimulates the

Application special dyes allows в

An atheromatous plaque consists of a fibrous covering

Progression of atheromatous changes leads to destruction of the plaque

The ulcerative intimal defect is often covered by thrombotic

Foci of calcifications in atheromatous masses, fibrous tissue, in

CLINICAL AND ANATOMICAL FORMS OF ATHEROSCLEROSIS

- true aneurysm; in others, adjacent tissue and hematoma - false

Hypertension (primary, or essential, idiopathic hypertension) is a

According to this, two main forms of hypertension are distinguished

By the nature of the course of hypertension is divided into malignant

• plasma saturation or fibrinoid necrosis of its wall;

In the benign form of hypertension, three stages with certain

Figure 2. Stages of development of hypertension.

Preclinical stage of hypertension

Stage of pronounced widespread morphologic changes of

Stage of secondary changes in internal organs

by thromboembolism or arterial thrombosis. Arteriolonecrosis

Arterioles and capillary loops of the tubules with fibrinoid

As a result of insufficient blood supply and hypoxia, the tubule

Changes in the eyes in hypertension are secondary and associated

► CORONARY ARTERY DISEASE HEART◄

Coronary heart disease (CHD) is a group of diseases caused by

Figure 3. Classification of ischemic heart disease.

Myocardial ischemic dystrophy (acute

The myocardium is flabby and pale, sometimes mottled and

Dilatation of capillaries, stasis and sludge phenomenon of

Figure 4. Classification of myocardial infarction.

Myocardial infarction is commonly categorized according to a

• by prevalence: when the endocardium is involved in the necrotic

Morphogenesis of myocardial infarction

The area of necrosis is delimited from the preserved

3. Scarring stage (organization):

Infarct organization occurs both from the demarcation zone and

Fig. 5. Schematic representation of changes in myocardial infarction: A -

D - 3 weeks (peripheral areas of infarction are formed by granulation tissue

Cardiomyopathies are a group of diseases based on primary

There are primary (idiopathic) and secondary diseases

Figure 6. Classification of primary cardiomyopathies.

• Hypertrophic (constrictive) cardiomyopathy is a pronounced

sections of the left ventricle, resulting in subaortic narrowing;

Cerebrovascular diseases - a group of diseases characterized by

Figure 7. Classification of cerebrovascular diseases.

Peuvmučecue diseases (cucumeme diseases of the medulla) are

The emuologuucccal factors common to rheumatic diseases are: