Path Anat Part 1

PRACTICAL GUIDE
ON PATHOLOGICAL ANATOMY
For 3rd year students of medical faculty
O.V. Lesnichaya, I.V. Samsonova
Vitebsk, 2012
Class 1
Theme: DYSTROPHY AS A PATHOLOGICAL PROCESS.
PARENCHYMATOUS DYSTROPHIES
1. Study the questions:

1. Classification of dystrophies.
2. Morphogenetic mechanisms of dystrophies.
3. Parenchymatous protein dystrophies: etiology, pathogenesis, morphogenesis,
outcomes, effects on organism.
a) Hyaline degeneration.
b) Hydropic (vacuolar) degeneration.
c) Keratin dystrophy (keratinization).
4. Parenchymatous lipid dystrophies: etiology, pathogenesis, morphogenesis,
outcomes, effect on organism.
5. Parenchymatous carbohydrate dystrophies: etiology, pathogenesis,
morphogenesis, outcomes, effect on the organism.
2. Theoretical part.
PATHOLOGY is the study (logos) of diseases (pathos). It is a discipline in-
volving both basic science and clinical practice and is devoted to the study of the
structural and functional changes in the cells, tissues, and organs that underlie dis-
eases.
The discipline so called Pathology has other names as well: pathological
anatomy, pathomorphology, morbid anatomy, anatomic pathology, histopathology,
surgical pathology etc. In our country this discipline is called Pathological anato-
my.
Pathological anatomy studies (1) causes of the disease (etiology), (2) the mech-
anisms of its development (pathogenesis), (3) the structural alterations induced in the
cells, organs and tissues of the body (morphological changes), and (4) the functional
consequences of the morphologic changes (clinical significance).
CELLULAR INJURY
Etiology of cellular injury
The causes of cellular injury, reversible or irreversible, may be broadly classi-
fied into two large groups:
1. Genetic causes.
2. Acquired causes.
The acquired causes of disease comprise the vast majority of common diseases
and can be further categorized as follows:
1. Physical agents (mechanical trauma, thermal trauma, ultraviolet and ionizing
radiation, rapid changes in atmospheric pressure).
2. Chemical agents and drugs.
3. Infectious agents.
4. Immunologic agents.
5. Nutritional derangements.
6. Physiologic factors.
ACUTE CELL INJURY
Reversible cellular injury is characterized by the ability of the cell to return to
its normal state after withdrawal of an acute stress.
Reversible injury is manifested by hydropic swelling of the cell (cellular ede-
ma), dilation of endoplasmic reticulum, and detachment of ribosomes from the granu-
lar endoplasmic reticulum, dissociation of polysomes into monosomes, mitochondria
swelling and enlargement, blebs of plasma membrane, nucleolar alterations with dis-
aggregation of granular and fibrilar elements.
Irreversible cellular injury or cellular death is necrosis and apoptosis.
Morphogenetic mechanisms of intra- and extracellular accumulations
Mechanisms of the development of intra- and extracellular (stromal) degenera-
tions (dystrophies) are as follows:
1. Infiltration redundant accumulation (deposition) of metabolites into the
cells and extracellular matrix.
2. Decomposition (phanerosis) disintegration of membranous structures of
the cells and extracellular matrix.
3. Abnormal synthesis synthesis of abnormal substances in the cells and tis-
sues.
4. Transformation formation of one type of metabolic product from common
initial substances for proteins, fats and carbohydrates.
INTRACELLULAR ACCUMULATIONS (PARENCHYMATOUS
DEGENERATIONS OR DYSTROPHIES)
Intracellular accumulations are the accumulation of abnormal amounts of
various substances in the cells. The stockpiled substances fall into three categories:
1. Normal cellular constituents accumulated in excess, such as fluids, lipids,
proteins, and carbohydrates.
2. An abnormal substance such as a mineral, or a product of abnormal metabo-
lism.
3. A pigment or an infectious product.
Parenchymatous degenerations occur in functional cells such as: cells of the
liver, kidneys, myocardium and are characterized by accumulation in their cytoplasm
proteins, fats and carbohydrates. It is accompanied by decrease (reduction) of func-
tion of enzymatic systems and occurrence of structural changes in cells. The most
often causes of parenchymal dystrophies are hypoxia, intoxication, and also enzy-
mopathy a genetically determined disease at which an inconsistency of enzymic
systems in cells is observed. There is an accumulation of any product of metabolism
in cells at enzymopathy. Such diseases are named as storage diseases.
PARENCHYMATOUS PROTEIN DYSTROPHIES
There are four kinds of intracellular protein dystrophies:
1. Granular degeneration. Gross appearance of organs with this dystrophy is
described as muddy or dim swelling. Cross-sectionally, the organs are dim, swol-
len. Microscopically, there are tiny protein pinkish granules in cytoplasm of cells. On
electronic examination there is the presence of electron dense granules in cytoplasm
of cells (these granules are enlarged in mitochondria).
2. Hyaline-drop dystrophy is characterized by the aggregation of small pro-
tein granules in the cytoplasm of cells. It is not determined macroscopically. This
dystrophy occurs in kidneys, liver and myocardium. Hyaline droplets in the proximal
tubular epithelial cells are seen in cases of excessive reabsorption of plasma proteins.
The cytoplasm of plasma cells shows pink hyaline inclusions called Russell's bodies
representing synthesized immunoglobulins. Mallory's body or alcoholic hyaline in
hepatocytes is intracellular accumulation of intermediate filaments of cytokeratin.
The outcome is negative. Focal or total coagulative necrosis develops.
3. Hydropic (cloudy, vacuolar, balloon) dystrophy is characterized by accu-
mulation of cytoplasmic fluid within the cell with cytoplasmic vacuolation. The
common causes are bacterial toxins, chemicals, poisons, burns, and high fever. The
affected organ such as kidney, liver or heart muscle enlarges. The cut surface bulges
outwards and is slightly opaque. Microscopically: the cells are swollen. Small clear
vacuoles are seen in the cells. These vacuoles represent distended cisterns of the en-
doplasmic reticulum.
The outcome is negative, because focal or total colliquative cellular necrosis
occurs.
4. Keratoid (horny) dystrophy is characterized by increased production of
keratin substances. This process can be local and general. The intracellular keratin
may be located in epidermis of skin. Leucoplakia means keratinization of mucosa.
Leucoplakia may lead to malignization. For example, it may lead to squamous cell
carcinoma development with or without keratinization. The groups of keratinized
cells can be found in the center of squamous cell carcinoma areas. These cell com-
plexes look like rose color homogenous masses called "cancer pearls".
INTRACELLULAR FATTY DEGENERATIONS
Intracellular fatty dystrophies are the abnormal accumulations of triglycer-
ides within parenchymal cells. The heart, liver, kidneys are damaged most frequently.
The main causes of fatty dystrophy are hypoxia and intoxication, which can
be caused by:
1. Excess alcohol consumption.
2. Chronic cardiovascular and chronic pulmonary insufficiency.
3. Cachexia, avitaminosis.
4. Infections (e.g. diphtheria, tuberculosis).
5. Late period of pregnancy.
6. Starvation.
7. Malnutrition.
8. Toxins (e. g. carbon tetrachloride, chloroform).
9. Certain drugs (e. g. administration of estrogen, steroids, tetracycline).
In the case of cell injury by chronic alcoholism, many factors are implicated
with increased lipolysis, increased free fatty acid synthesis, decreased triglyceride
utilization, decreased fatty acid oxidation to ketone bodies, and block in lipoprotein
excretion.
In an alcoholic who has not developed progressive fibrosis in the form of cir-
rhosis, the enlarged fatty liver may return to normal if the person becomes teetotal.
Morphological features of fatty change:
Fat in the tissue can be demonstrated by frozen section followed by fat stains
such as Sudan 3 (red or orange color) or Sudan 4 (black color), oil red O and osmic
acid.
1. Fatty dystrophy of the liver
Macroscopically, the fatty liver is enlarged with rounded margins.
The cut surface bulges slightly and is pale-yellow and is greasy to touch. It is
called goose liver.
Microscopically: there are numerous lipid vacuoles in the cytoplasm of
hepatocytes. The vacuoles are initially small (microvesicular), but with progression
of the process, the vacuoles become larger pushing the nuclei to the periphery of the
cells (macrovesicular).
The hepatocytes laden with large lipid vacuoles may rupture and lipid vacu-
oles coalesce to form fatty cysts. Infrequently, lipogranulomas may appear.
2. Fatty dystrophy of the heart
It is also called tiger heart.
Macroscopically, the heart is enlarged; the heart cavities are stretched, flabby.
Microscopically, we can see dust-like fatty vacuoles in the cardiomyocytes.
It is observed in the papillary muscles and trabecules of the ventricles in the
form of bands (surrounding the veins).
3. The kidneys look like large white kidney. They are enlarged, flabby. The
cortical substance is gray with yellow drops.
Outcomes of fatty degenerations are rarely reversible. Necrosis or sclerosis
may develop.
INTRACELLULAR CARBOHYDRATE DEGENERATIONS
Carbohydrates are divided into 3 groups:
1. Polysaccharides (glycogen).
2. Mucopolysaccharides.
3. Glycoproteids (mucin, mucoid).
There are several special reactions for identification of these carbohydrates.
Best's carmine and PAS (periodic acid-Schiff) staining may be employed to confirm
the presence of glycogen in cells. Polysaccharides and mucopolysaccarides are
stained dark pink or red. Staining according to Haile is used for glycoproteides identi-
fication. Glycoproteides are stained blue.
A c c u mu l a t i o n o f g l y c o g e n
Excessive intracellular deposition of glycogen usually occurs in patients with
an abnormality of either glucose or glycogen metabolism.
Morphological features appearance of glycogen masses as clear vacuoles
within the cytoplasm developed with special stain (PAS-reaction).
In diabetes mellitus the main example of this disorder the red color gran-
ules of glycogen can be found with large magnification in the epithelial cells of Hen-
ley's loops and renal tubules.
Amount of glycogen in the tissues reduces sharply (e.g. in the liver) which
causes its fat infiltration (fatty liver degeneration).
Mucoid change
Mucus secreted by mucous glands is a combination of protein complexes with
mucopolysaccharides. Mucin, a glycoprotein, is the main constituent. Mucin is nor-
mally produced by epithelial cells of mucous membranes and mucous glands, as well
as by some connective tissues like in the umbilical cord. Epithelial mucin stains posi-
tively with periodic acid-Schiff (PAS), while connective tissue mucin does not but
stains positively with colloidal iron. However both are stained by alcian blue.
Epithelial mucin is associated with:
Catarrhal inflammation of mucous membrane (e.g. of respiratory tract, ali-
mentary tract, uterus).
Obstruction of ducts leading to mucocele in the oral cavity, chronic appendi-
citis and gall bladder.
Cystic fibrosis of the pancreas or mucoviscidosis.
Mucin secreting tumors (e.g. of ovary, stomach, large bowel etc.).
STORAGE DISEASES
There are a lot of diseases, which are due to hereditary factors and are connect-
ed with metabolism disturbance. These diseases are called storage diseases or enzy-
mopathy.
A few general comments can be made about all storage diseases:
All the storage diseases occur as a result of autosomal recessive, or sex-(X-)
linked recessive genetic transmissions.
Most of the storage diseases are lysosomal storage diseases. Out of the glyco-
gen storage diseases, only type II (Pompe's disease) is due to lysosomal enzyme defi-
ciency.
According to the type of metabolic disturbance storage diseases have been
classified into:
Proteinoses
Lipidosis
Glucogenoses
The type of proteinoses, lipidosis and glycogenoses depends on the defect in
the enzyme. The most frequent lipidoses are Gaucher's disease, Niemann-Pick dis-
ease.
GAUCHER'S DISEASE
This is an autosomal recessive disorder in which there is a deficiency of lyso-
somal enzyme, glucocerebrosidase, which normally cleaves glucose from ceramide.
This results in lysosomal accumulation of glucocerebroside (ceramide-glucose) in
phagocytes of the body and sometimes in the neurons. The main sources of gluco-
cerebroside in phagocytic cells of the body and sometimes in the neurons are the
membrane glycolipids of old leukocytes and erythrocytes, while the deposits in the
neurons consist of gangliosides.
Clinically, there are 3 types of Gaucher's disease:
1. Type 1 or classic form is the adult form of the disease in which there is stor-
age of glycocerebrosides in the phagocytes of the body, principally involving the
spleen, liver, bone marrow and lymph nodes. This is the most common type compris-
ing 80% of all cases of Gaucher's disease.
2. Type II is the infantile form in which there is progressive involvement of the
central nervous system.
3. Type III is the juvenile form of the disease having features in between type I
and type II, i.e. they have systemic involvement like in type I and progressive in-
volvement of the central nervous system (CNS) as in type II.
M O R P H OL OGY
In addition to involvement of different organs and systems (splenomegaly,
hepatomegaly, lymphadenopathy, bone marrow and cerebral involvement), a few
other features include pancytopenia, or thrombocytopenia secondary to hypersplen-
ism, bone pains and pathological fractures.
Microscopically, large number of characteristically distended and enlarged
macrophages called Gaucher cells are found in the spleen, liver, bone marrow and
lymph nodes, and in the case of neuronal involvement, in the Virchow-Robin space.
The cytoplasm of these cells is abundant, granular and fibrillar resembling crumpled
tissue paper. They have mostly a single nucleus but occasionally may have two or
three nuclei. These cells often show erythrophagocytosis and are rich in acid phos-
phatase.
NIEMANN-PICK DISEASE
This is also an autosomal recessive disorder characterized by accumulation of
sphingomyelin and cholesterol.
The majority of the cases (about 80%) have deficiency of sphingomyelinase,
which is required for cleavage of sphingomyelin, while a few cases probably result
from deficiency of an activator protein.
The condition presents in infancy and is characterized by hepatosplenomeg-
aly, lymphadenopathy and physical and mental underdevelopment.
About a quarter of patients present with familial amaurotic idiocy with char-
acteristic cherry-red spots in the macula of the retina.
The storage of sphingomyelin and cholesterol occurs within the lysosomes,
particularly in the cells of mononuclear phagocyte system.
The cells of Niemann-Pick disease are somewhat smaller than Gaucher cells
and their cytoplasm is not wrinkled but is foamy and vacuolated which stains posi-
tively with fat stains. These cells are located in the spleen, liver, lymph nodes, bone
marrow, lungs, intestine and brain.
The most frequent glycogen storage diseases or glycogenoses are Pompe's dis-
ease, Mc Ardle's disease and Gierkes disease. There is a defective metabolism of
glycogen due to genetic disorders.
Pompe's Disease. This is also an autosomal recessive disorder due to deficien-
cy of a lysosomal enzyme, acid mahase. Its deficiency results in accumulation of gly-
cogen in many tissues, most often in the heart and skeletal muscles leading to cardio-
megaly and hypotonia.
Mc Ardle's Disease. The condition occurs due to deficiency of muscle phos-
phorylase resulting in accumulation of glycogen in the muscle (deficiency of liver
phosphorylase). The disease is common in 2nd 4th decades of life and is character-
ized by painful muscle cramps, especially after exercise, and detection of myoglobi-
nuria in half of the cases.
Gierke Disease. This condition is inherited as autosomal recessive disorder due
to deficiency of enzyme glucose-6-phosphatase. In the absence of glucose-6-
phosphatase, excess of normal type of glycogen accumulates in the liver and also re-
sults in hypoglycemia due to reduced formation of free glucose from glycogen. As a
result, fat is metabolized for energy requirement leading to hyperlipoproteinemia and
ketosis. Another change due to deranged glucose metabolism is hyperuricemia. The
disease manifests clinically in infancy with failure to grow and stunted growth. Most
prominent feature is enormous hepatomegaly with intracytoplasmic and intranuclear
parenchymatous glycogen. The kidneys are also enlarged and show intracytoplas-
mic glycogen in tubular epithelial cells. Other features include gout, skin xanthomas
and bleeding tendencies due to platelet dysfunction.
The outcome of storage diseases is unfavorable because of its insufficiency of
the respective organ.
3. Class work.
I. Study the macropreparations:

4. Goose liver. Liver is enlarged in size, flabby, pale-yellow and is greasy
to touch. Name the causes and morphological mechanisms of this dystrophy.
2 Toxic dystrophy of liver. Liver is enlarged in size, flabby, grey-yellow
(necrotic foci have grey color; hepatocytes with fatty parenchymatous dystrophy
have yellow color). Name the possible morphogenetic mechanisms of liver toxic
dystrophy development.
II. Study the micropreparations:

11 Granular changes of kidney tubule epithelium cytoplasm (st.
hematoxylin and eosin) Using large magnification, pay attention to the sizes of
tubuli lumen, state of epithelium cytoplasm (tiny pink granules are present in
cytoplasm of epithelial cells shown by the arrow). Pay attention that granular
dystrophy is not true dystrophy. It is a compensatory-adaptative process which is
reversible. Draw.
23 Lipid dystrophy of the liver. (st. Sudan 3). Using large magnification,
find the groups of hepatocytes with dystrophic changes (intracellular lipid droplets
that are dark orange). Draw.
68. Keratin dystrophy of keratinized stratified epithelium (st.
hematoxylin and eosin). Using small magnification, pay attention to the severe
thickness of keratin layer [a] of skin epidermis [b]. Draw.
III. Complete the tables:
Structural changes of organs in protein and fatty parenchymatous dystrophies

Kinds of Microscopic changes in the organs
parenchymatous heart liver kidney others
dystrophy
Fatty dystrophy Tiger heart Micro- and macrovesicular Pulverulent or -
microvesicular droplets of fat in hepatocytes, microvesicular
droplets of fat in at times, with rapture of large droplets of fat in
myocardial lipid vacuoles. Infrequently, epithelial cells of
fibers lipogranulomas may appear convoluted tubules
Parenchymatous protein dystrophies

Dystrophy type Mechanism of Outcomes
development
Hydropic dystrophy Decomposition May be either entirely reversible upon
(phanerosis) removal of the injurious agent or irreversible
(finishing by colliquative necrosis) under the
constant influence of injurious agent
4. Clinical tasks.
1. A patient with follicular tonsillitis had temperature rise up to 390, severe tachycardia,
and minute protein in urine. After the recovery of the patient the cardiac function and
urine analysis came to norm.
1. What pathological process occurred in the myocardium and kidneys?
2. What pathological changes in these organs can be diagnosed grossly?
3. What pathological changes in these organs can be diagnosed microscopically?
4. What is the morphogenetic mechanism of the dystrophy in kidneys and myocardi-
um?
5. Why did the cardiac and kidney function come to norm after the recovery of the
patient?
2. A patient had glomerulonephritis with nephrotic syndrome. 20 g of protein was

detected in the urine analysis of the patient per day for a long period of time. For ver-
ification of diagnosis a puncture biopsy of kidney was made.
1. What kinds of parenchymatous protein dystrophy can be diagnosed in biopsy
of proximal and distal convoluted tubules epithelium?
2. Are these changes reversible?
3. A patient with chronic myeloid leucosis had severe anemia (the level of hemo-
globin was 60 g/l during 6 months). On examination, heart sounds muting and cardiac
left border dilation were found. The patient died of progressive cardiac failure.
1. What kind of dystrophy in the myocardium was the morphological substrate
of cardiac decompensation?
2. What is the morphogenetic mechanism of its development?
3. What gross changes in the heart can be found at autopsy?
4. What changes of myocardial cells can be found microscopically?
5. What stain is necessary to use for visualization of these changes?
4. A woman with obesity resulting from sedentary life and excess fatty food intake
complained of heavy feeling in the area below the ribs, occasional nausea and feeling
of bitterness in the mouth. On palpation, the dilation of liver borders was revealed.
1. What kind of dystrophy occurred in liver?
2. What are the morphogenetic mechanisms of its development?
3. What microscopical changes can be found in puncture biopsy of the liver of
the patient?
4. What stain is necessary to use for visualization of these changes?
5. A woman appealed to a physician for medical aid. She complained of weakness,

rapid fatigability, sleepiness, giddiness, tinnitus, dyspnea, palpitation, dysgeusia, oc-
casional nausea, heavy feeling in the area below the ribs, brittleness of nails, and loss
of hair. On examination, pallor of skin and mucous membranes, arterial hypotension,
systolic murmur, a fall in hemoglobin concentration down to 80 g/l and a reduction of
RBC count down to 2.4*1012/l were found. Leukocytes and platelets count, leu-
kogram were normal. The serum iron was reduced down to 30g/dl. The liver was
slightly enlarged on palpation.
1. What pathological process occurred in the liver and in the heart?
2. What was the reason for this process?
3. What are the morphogenetic mechanisms of its development?
4. What stain is necessary to use for visualization of this process?
ANSWERS
Number of question with answer
1 1 2 3 4 5
Granular degenera- Muddy or dim There are protein Decomposition Reversible
tion of cytoplasm swelling granules in paren- (phanerosis) process
chymatous cells
2 Granular degenera- Granular degenera-
tion of cytoplasm tion is reversible,
and hyaline-drop hyaline-drop dys-
dystrophy trophy is irreversi-
ble
3 Parenchymatous Decomposition Tigers heart, flab- Fatty paren- Sudan 3 or
fatty dystrophy (phanerosis) biness of heart chymatous Sudan 4
dystrophy in
myocardial
fibers
4 Parenchymatous Transformation Micro- and macrove- Sudan 3 or
fatty dystrophy, sicular droplets of fat Sudan 4
simple liver obesity in hepatocytes
5 Parenchymatous Hemic hypoxia Decomposition (phan- Sudan 3 or
fatty dystrophy owing to iron- erosis) Sudan 4
deficiency anemia
5. Self assessment.
1. One of the manifestations of metabolic derangements in cells is:
1. Apoptosis
2. The intracellular accumulation of abnormal amounts of various substances
3. Hypertrophy
4. Metaplasia.
5. Atrophy
2. One of the possible causes of intracellular accumulation of metabolic substances is:
1. Genetic defects
2. Inflammation
3. Embolism
4. Necrosis
5. Activation of oncogenes
3. Substances that accumulate within parenchymal cells in steatosis are:
1. Cholesterol
2. Apoproteins
3. Triglycerides
4. Vitamins
5. Ketone bodies
4. Fatty change is often seen in all of the following organs, EXCEPT:
1. Liver
2. Heart
3. Kidney
4. Muscles
5. Lung
5. The causes of steatosis include all of the following pathologic states, EXCEPT:
1. Obesity
2. Anoxia
3. Inflammation
4. Protein malnutrition
5. Intoxication
6. The causes of fatty liver include all diseases, EXCEPT:
1. Obesity
2. Alcohol abuse
3. Diabetes mellitus
4. Hepatitis virus B
5. Anoxia
7. The stain that is used to identify fat is:
1. Hematoxylin and eosin stain
2. Sudan III stain
3. Congo red stain
4. PAS reaction
5. Metachromatic stain
8. The stain that is used to identify glycogen is:
1. Hematoxylin and eosin stain
2. Sudan III stain
3. Congo red stain
4. PAS reaction
5. Metachromatic stain
9. The fatty liver has all pathologic features, EXCEPT:
1. Enlarged
2. Yellow
3. Red
4. Soft
5. Greasy
10. Fatty change is seen by light microscopy as:
1. Intracellular granules
2. Basophilic granules
3. Extracellular granules
4. Vacuoles in the cytoplasm around the nucleus
5. Eosinophilic granules
11. The most common cause of fatty change in the heart is:
1. Inflammation
2. Neoplasia
3. Hypoxia
4. Amyloidosis
5. Autoimmune diseases
12. Fatty change in the heart is characterized by:
1. Red heart
2. Small size of heart
3. Tiger heart
4. Solid heart
5. Goose heart
13. All of the following mechanisms cause intracellular accumulation, EXCEPT:
1. Abnormal metabolism
2. Protein mutation
3. Inflammation
4. Enzyme deficiency
5. Ingestion of indigestible materials
14. Vacuolar degeneration of hepatocytes is caused by:
1. Accumulation of water and cellular swelling
2. Retaining of biliary material
3. Accumulation of iron or copper substances
4. Accumulation of fat droplets
5. Accumulation of lipofuscin
15. Vacuolar degeneration of hepatocytes results from:
1. Viral hepatitis
2. Alcoholic liver disease
3. Biliary material accumulation
4. Obesity
16. All of the following features characterize the ballooning degeneration of hepatocytes,
EXCEPT:
1. Swollen cells
2. Edematous appearance
3. Clumped cytoplasm
4. Large droplets of fat
5. Large clear spaces
17. The disorder of glycogen metabolism is associated with:
1. Amyloidosis
2. McArdle disease
3. Obesity
4. Hemosiderosis
5.Hemochromatosis
18. Diabetes mellitus is characterized by the accumulation of glycogen in all cells,
EXCEPT:
1. Epithelial cells of the proximal tubules
2. Liver cells
3. -cells of the islets of Langerhans
4. Smooth muscle cells
5. Heart muscle cells
19. Hepatic cell injury induced by CCl4 is characterized by all of the following changes,
EXCEPT:
1. Lipid peroxidation
2. Disaggregation of ribosomes
3. Depletion of intracellular lipids
4. Influx of calcium
5. Mitochondrial damage
20. The causes related to CCl4-induced hepatic ceil injury are all of the following,
EXCEPT:
1. Processing by mixed function oxidases and free radical formation
2. Free radical formation - lipid peroxidation of intracellular membranes
3. Failure of protein synthesis disaggregation of ribosomes
4. Decreased apolipoprotein synthesis with intracellular lipid accumulation
5. Plasma membrane damage with mitochondrial calcification
Answers
1 2 11 3
2 1 12 3
3 3 13 3
4 5 14 1
5 3 15 1
6 4 16 4
7 2 17 2
8 4 18 4
9 3 19 3
10 4 20 3
Class 2
Theme: Mesenchymal dystrophies
1. Classification of mesenchymal dystrophies according to the kind of metabolic
disturbances.
2. Mucoid and fibrinoid swelling: etiology, pathogenesis, morphogenesis, out-
comes, effect on the organism.
3. Hyalinosis: etiology, pathogenesis, morphogenesis, outcomes, effect on the
organism.
4. Amyloidosis: etiology, pathogenesis, morphogenesis, outcomes, effect on the
organism.
5. Classification of amyloidosis.
6. Localization of amyloidosis in tissues, organs. Gross appearance of organs
with amyloid deposition.
7. Disturbances of neutral fat metabolism: etiology, pathogenesis, morphogene-
sis, outcomes, effect on the organism. The causes and the mechanism of general
obesity development.
8. Disturbances of cholesterol metabolism.
9. Mucous edema of tissues: pathogenesis, the causes and outcomes.
EXTRACELLULAR ACCUMULATIONS (MESENCHYMAL
DYSTROPHIES)
Mesenchymal degenerations occur in the connective tissue and vascular walls
as a result of metabolic disturbances.
MESENCHYMAL PROTEIN DYSTROPHIES
Protein mesenchymal dystrophies occur as mucoid swelling, fibrinoid swelling,
hyalinosis and amyloidosis.
The first three types are the stages of connective tissue disorganization. The
causes of mucoid swelling, fibrinoid swelling and hyalinosis are the same as they are
the stages of one process. They are caused by immunopathological and autoimmune
states, hypoxia, infections. These types of connective tissue disorganization are fre-
quently observed in hypertension, rheumatism and other diseases of the connective
tissue accompanied by immune disturbances as well as in allergic diseases, diabetes
mellitus, etc. In the majority of cases the arterial walls, heart valves, endocardium,
epicardium, articular connective tissue are involved.
1. Mucoid swelling
Mucoid swelling is superficial reversible disorganization of the connective
tissue.
These processes are associated with swelling of collagen fibers, increased
vascular permeability (due to the accumulated glucosaminoglycans (GAG) action)
and plasmorrhagia.
Microscopic examination shows metachromasia (the ability of substance to
change the original colour of stain). Under normal conditions the ground substance is
basophilic in toluidine blue staining. In the case of metachromasia staining with tolu-
idine blue demonstrates reddish coloring.
Macroscopic appearance is not changed.
The outcome may be reversible. In other cases, the development of fibrinoid
swelling is possible.
2. Fibrinoid swelling
Fibrinoid swelling is deep irreversible connective tissue disorganization.
Fibrinoid is formed as a result of the ground substance destruction and a
severer increase of vascular permeability.
The gross appearance of the organs is slightly changed.
The main signs are revealed microscopically: the bands of collagen fibers are
destroyed, homogenous, impregnated with plasma proteins.
Metachromasia is not apparent due to GAG depolymerization in the ground
substance.
Fibrinoid swelling may be generalized (in systemic diseases of the connective
tissue) and localized (in chronic inflammation).
The outcomes are fibrinoid necrosis, sclerosis or hyalinosis.
3. Hyaline changes (hyalinosis)
Hyalinosis (hyaline changes) is derived from Greek word hyalos mean-
ing transparent, glass-like. It usually refers to an alteration within cells or in the ex-
tracellular matrix, which gives a homogenous, glassy, pink appearance in routine his-
tological sections stained with hematoxylin and eosin.
Hyalinosis occurs as a result of plasma infiltration, fibrinoid swelling, in-
flammation, necrosis, and sclerosis.
Hyalinosis is classified according to its localization (vascular hyalinosis and
connective tissue hyalinosis) and propagation (generalized and localized).
Vascular hyalinosis involves the arterioles and small arteries. In their walls,
the endothelium, basement membranes, and smooth muscle cells are damaged.
Three types of vascular hyaline are distinguished depending on the pathoge-
netic character of its formation: l) simple, 2) lipohyaline, 3) compound hyaline.
Microscopic study of the arteries demonstrates thickened walls with sharply
narrowed or obliterated lumen. At first, hyaline accumulates in subendothelial area of
the vascular wall, and then it destroys elastic membranes and middle layer.
In long-standing hypertension and diabetes mellitus, the walls of arterioles,
especially in the kidney, become hyalinized, owing to imbibition with plasma pro-
teins and deposition of basement membrane material.
Hyalinosis of connective tissue is usually localized; it occurs in scars, adhe-
sions, in the areas of chronic inflammation (e.g. glazed spleen).
Hyalinosis is irreversible dystrophy.
Functional significance of hyalinosis is different. Thus, vascular hyalinosis
may lead to atrophy or sclerosis, infarction of organs. Local hyalinosis in the cardiac
valves results in heart defects.
AMYLOIDOSIS
Amyloidosis is the term used for a group of diseases characterized by extra-
cellular deposition of fibrillar proteinaceous substance called amyloid.
Nature and etiology
Amyloid is composed of 2 main types of complex proteins:
1. F-component fibril proteins comprise about 95% of amyloid.
2. P-component constituting the remaining 5% of amyloid.
Fibril Proteins
By electron microscopy the major component of amyloid material (about 95%)
consists of meshwork of fibril proteins. Chemically, 2 major forms of amyloid fibril
proteins are identified which have different origins and are seen in distinct clinico-
pathologic conditions:
AL (amyloid light chain) protein.
AA (amyloid associated) protein. It is derived from larger precursor pro-
tein in the serum called SAA (serum amyloid-associated protein).
Other proteins. In addition a few other forms of proteins are also found in
some types of amyloid:
Transthyretin (ATTR).
A2-microglobulin (A2m).
-amyloid protein (A).
Hormone precursors such as procalcitonin and pro-insulin (amyloid en-
docrine) and keratin have also been reported in amyloids.
P-Component
The second component of amyloid is non-fibrillar P-component that constitutes
about 5% of amyloid material. It is synthesized in the liver and is present in all types
of amyloid. It is a glycoprotein resembling the normal serum 1-glycoprotein and is
PAS-positive.
Classification of amyloidosis
A clinicopathologic classification is currently widely used. According to this
classification, amyloidosis can be divided into 2 major categories, each found i n dis-
tinct clinical settings.
A. Systemic (generalized) amyloidosis
1. Primary amyloidosis.
It is one of two types of systemic or generalized amyloidosis.
Primary amyloidosis associates with some form of plasma cell dyscrasias
(most commonly multiple myeloma and less often other monoclonal paraproteinemic
hemoblastoses) and contains AL-protein.
Primary amyloidosis is often severe in the heart, bowel, skin, skeletal mus-
cle, and less often in the solid abdominal viscera.
This type of amyloidosis is the most common form in the world.
2. Secondary (reactive) amyloidosis.
The second form of systemic or generalized amyloidosis is reactive or sec-
ondary in which the fibril proteins contain AA amyloid.
Secondary or reactive amyloidosis occurs as a complication of chronic infec-
tious or noninfectious inflammatory conditions associated with tissues destruction
such as tuberculosis, bronchiectasis, chronic osteomyelitis, chronic pyelonephritis,
leprosy, autoimmune disorders (rheumatoid arthritis, dermatomyositis and scleroder-
ma), inflammatory bowel disease (ulcerative colitis and Crohn's disease) and some
tumors (renal cell carcinoma and Hodgkin's disease).
Secondary amyloidosis is typically distributed in solid abdominal viscera like
the liver, spleen, kidneys and adrenal glands. Secondary reactive amyloidosis is seen
less frequently in developed countries due to containment of infections before they
become chronic, but this is the most common type of amyloidosis in underdeveloped
and developing countries of the world.
3. Familial amyloidosis.
Familial amyloidosis is seen in patients with familial Mediterranean fever and
familial hereditary polyneuropathic amyloidosis.
Familial Mediterranean fever is an autosomal recessive disease. The condi-
tion is characterized by periodic attacks of fever and polyserositis. Amyloidosis oc-
curring in this case is AA type.
Hereditary polyneuropathic amyloidosis is an autosomal dominant disorder in
which amyloid is deposited in the peripheral and autonomic nerves. This type of
amyloid is derived from transthyretin (ATTR).
B. Localized Amyloidosis
Senile cardiac amyloidosis is seen in 50% of people above the age of 70
years. The deposits are seen in the heart and aorta.
Senile cerebral amyloidosis is deposition of amyloid material in the walls of
cerebral blood vessels in 60% of people above the age of 70 years. Patients with Alz-
heimer's disease also develop amyloid in the senile plaques.
Endocrine amyloidosis. Some endocrine tumors are associated with micro-
scopic deposits of amyloid in medullary carcinoma of the thyroid gland, and islet cell
tumor of the pancreas.
M O R P H OL OGY
Macroscopically, the affected organs are often enlarged and firm and have a
waxy appearance. If the deposits are sufficiently large, painting the cut surface with
iodine imparts a yellow color that is transformed to blue violet after the application
of sulfuric acid.
The histologic diagnosis of amyloid is based almost entirely on its staining
characteristics:
H & E. Amyloid by light microscopy with haematoxylin and eosin staining
appears as extracellular, homogeneous, structureless and eosinophilic hyaline materi-
al.
Metachromatic stains (Rosaniline Dyes). Amyloid has the property of meta-
chromasia, i.e. the dye reacts with amyloid and undergoes a color change. Meta-
chromatic stains employed are rosaniline dyes such as methyl-violet and crystal-
violet, which impart rose-pink coloration to amyloid deposits.
Congo red. All types of amyloid have affinity for Congo red stain. The stain
may be used on both gross specimens and microscopic sections; amyloid stains an
orange color. The stain can also be used to distinguish between AL and AA amyloid
(primary and secondary amyloid respectively). After prior treatment with permang-
nate on the section, Congo red stain is repeated: in the case of primary amyloid (AL
amyloid), the Congo red positivity (congophilia) persists while it turns negative for
Congo red in secondary amyloid (AA amyloid).
Sulfated alcian blue. This is a nonspecific screening test and imparts blue-
green color to amyloid positive areas.
Immunohistochemistry. More recently, immunohistochemical stains can clas-
sify types of amyloid. Antibody specific for fibril protein gives positive immunoreac-
tivity.
Diagnosis of amyloidosis
Histological examination of biopsy material is the commonest and confirmato-
ry method for a diagnosis in a suspected case of amyloidosis. If renal manifestations
are present, kidney is the preferred site for biopsy. Otherwise, the commonly accessi-
ble sites such as rectum, gum, and more recently abdominal fat, are biopsied and are
followed by Congo red staining for confirmation.
Pathologic changes in organs
Amyloidosis of Kidneys
Amyloidosis of the kidneys is most common and most serious because of ill-
effects on renal function.
The deposits in the kidneys are found in most cases of secondary amyloidosis
and in about one third cases of primary amyloidosis.
The kidneys may be normal-sized, enlarged or terminally contracted due to
ischemic effect of vascular lumina narrowing. Cut surface is pale, waxy and translu-
cent.
Amyloid deposition occurs primarily in the glomeruli though it may involve
peritubular interstitial tissue and the walls of arterioles as well.
In the glomeruli, the deposits initially appear on the basement membrane of
the glomerular capillaries, but later extend to produce luminal narrowing and distor-
tion of the glomerular capillary tuft.
In the tubules, the amyloid deposits, likewise, begin close to the tubular epi-
thelial basement membrane.
The vascular involvement affects chiefly the walls of small arterioles and
venules, producing narrowing of their lumina and consequent ischemic effects.
Amyloidosis of Spleen
Two patterns are observed:
Sago spleen. Splenomegaly is not marked and cut surface shows character-
istic translucent pale and waxy nodules resembling sago grains and hence the name
appears. Microscopically, the amyloid deposits begin in the walls of the arterioles
of the white pulp and may subsequently replace the follicles.
Lardaceous spleen. There is a generally moderate to marked splenomegaly
(weight up to l kg). Cut surface of the spleen shows map-like areas of amyloid. Mi-
croscopically, the deposits involve the walls of splenic sinuses, the small arteries, and
the connective tissue of the whole pulp.
Amyloidosis of Liver. The liver is often enlarged, pale, waxy and firm. The
amyloid initially appears in the space of Disse, but later as it increases it compresses
the cords of hepatocytes.
Amyloidosis of Heart.
The heart is involved in systemic amyloidosis quite commonly more so in
the primary than in secondary systemic amyloidosis. It may also be involved in lo-
calized form of amyloidosis in very old patients.
Amyloidosis of the heart may produce arrhythmias due to deposition in the
conduction system. The heart shows tiny nodular deposits of amyloid underneath the
endocardium.
Later, there may be a pressure atrophy and impaired ventricular function,
which may produce restrictive cardiomyopathy.
Amyloidosis of Alimentary tract. Involvement of the gastrointestinal tract by
amyloidosis may occur at any level from the oral cavity to the anus. Rectal and gin-
gival biopsies are the common sites for diagnosis of systemic amyloidosis.
The prognosis for patients with generalized amyloidosis is poor. Those with
immunocyte-derived amyloidosis have a median survival of 2 years after diagnosis.
MESENCHYMAL FATTY DEGENERATIONS

Mesenchymal fatty infiltration is the deposition of mature adipose cells in
the stromal connective tissue. The condition occurs most often in patients with obesi-
ty.
As a rule it is a generalized process when the amount of fat in the depots in-
creases.
Depending on the excess of patients body weight compared to the norm, 4
degrees of obesity are defined:
1. If the patient's body weight increases by 20 - 29% 1st degree of obesity is
distinguished;
2. If the patient's body weight increases by 30 - 49% 2nd degree;
3. If the patient's body weight increases by 50 - 99% 3rd degree;
4. If the patient's body weight increases up to 100% and more 4th degree of
obesity.
The two commonly affected organs are the heart and the pancreas.
The damage to these organs is most significant.
Fat tissue covers the heart in subepicardial area and then invades the myocar-
dial stroma causing atrophy of myocardial fibers and sclerosis.
If the connective tissue does not grow, heart rupture in the area of fat growth
may occur.
In pancreatic lipomatosis beta-cell atrophy and diabetes mellitus are possible.
According to the etiology the following types of obesity are defined:
1. Primary (idiopathic);
2. Secondary.
There are several types of secondary obesity:
1. Alimentary.
2. Cerebral.
3. Endocrine.
4. Hereditary in Gierke's disease.
According to the patient's appearance, obesity may be
1. Symmetrical
2. Upper
3. Medial
4. Lower.
According to morphological peculiarities of adipose tissue, it may be:
1. Hypertrophic.
2. Hyperplastic.
In hypertrophic type adipose tissue enlarges due to increased volume of fatty
cells, in hyperplastic due to increase in their number. Obesity may be a severe com-
plication of endocrine and nervous diseases. Alimentary obesity is also unfavorable
for the organism. As a rule such patients develop ischemic heart disease.
Local enlargement of adipose tissue (lipomatosis) occurs in Dercum's disease
when painful fat nodes appear in the subcutaneous fat of the lower and upper extremi-
ties and trunk.
Sharp reduction in the amount of neutral fat in the whole organism is called ca-
chexia.
Disturbance in cholesterol and its esters metabolism causes atherosclerosis.
The wall of the vessel is thickened everywhere. It is much more thickened because of
atherosclerotic plaque formations, which are composed of lipids and fibrotic tissue.
MESENCHYMAL CARBOHYDRATE DEGENERATIONS
Mesenchymal carbohydrate degenerations occur due to disturbances of gly-
cosaminoglycan and glycoproteid metabolism. When glycoproteid metabolism is dis-
turbed, chromotropic substances are released from the protein bonds. They are accu-
mulated in the ground substance of the connective tissue. Collagen fibers change into
mucus-like mass.
Connective tissue mucin is associated with:
Mucoid or myxoid degeneration in some tumors (myxoma).
Neurofibromas, soft tissue sarcomas etc.
Myxomatous change in the dermis in myxedema.
Myxoid change in the synovium in ganglion on a wrist.
The condition results in colliquative necrosis with formation of cavities filled
with mucus.
Mucopolysaccharidoses (MPS)
Disturbance of glycosaminoglycans (GAG) is due to hereditary factors as in a
storage disease.
It is characterized by the deficiency of specific lysosomal enzyme involved in
the degradation of mucopolysaccharides or glycosaminoglycans.
Syndrome of MPS manifests in infancy or early childhood and involves mul-
tiple organs and tissues, chiefly connective tissues, liver, spleen, bone marrow, lymph
nodes, kidneys, heart and brain.
The mucopolysaccarides accumulate in mononuclear phagocytic cells, endo-
thelial cells, smooth muscle cells and fibroblasts. The material is finely granular and
PAS-positive by light microscopy.
By electron microscopy, it appears in the swollen lysosomes and can be iden-
tified biochemically as mucopolysaccharide.
The most frequent of them are Pfaundler-Hurler disease, or gargoylism. Its
cause is congenital defect of the enzyme determined GAG metabolism. This disease
is characterized by irregular skeleton growth, massive skull, heart defects, inguinal
and umbilical hernias, hepato- and splenomegaly, keratoleukoma (retina opacity).
3. Class work.

159. Rheumatic heart disease. Left parts of the heart are enlarged in size.
Mitral valve is deformed and covered by warty masses (thrombotic masses). There is
a hypertrophy of the left ventricle.
99. Arteriolosclerotic nephrosclerosis. Kidneys are decreased in size;
their surface is rough and tuberous. Kidney parenchyma is thin; the pelvo-calyces
system is dilated.
243. Sago spleen. Spleen is enlarged in size and firm. The cross section of
the spleen shows red inclusions (which are the places of amyloid depositions in folli-
cles) and lardaceous shine.
87. Kidney amyloidosis. Kidneys are enlarged in size, firm, have larda-
ceous shine. Later the development of secondary shrinkage of kidney is possible due
to nephrosclerosis.
143. Atherosclerosis of aorta. Intima of the aorta is irregular, rough, dim
and grey-brown due to atherosclerotic plaques, which are ulcerated and calcified. The
formation of thrombi on the surface of such plaques is possible.

13-.Hyalinosis of vessels and scar at the place of yellow body of the
ovary (st. hematoxylin and eosin). Note the hickness of the wall, changes in the in-
ternal and middle coats of arteries, narrowing of the vessels lumen [a]. Find the hya-
line deposition in the yellow body scar [b]. Draw.
a b
17-. Sago spleen (st. Congo red). Find the red deposition of amyloid
(shown by the arrow), pay attention to its shape (round) and localization (white pulp).
Draw.
15. Kidney amyloidosis. (st. Congo red). Deposition of amyloid is clearly
visible in the glomeruli [a]. Amyloid substances are revealed in the basement mem-
branes under the endothelium and tubular epithelium. Lumens of tubuli are extended
and contain cylinders [b]. Draw.
22. Heart obesity (st. Sudan 3). Study and describe. Note the localization
of lipid cells (under the epicardium and between myocardial fibers the last is shown
by the arrows). Note the differences between the simple heart obesity and lipid dys-
trophy of the myocardium. Draw.
27. Atherosclerosis of aorta (st. Sudan 3). Pay attention to lipid drops of
orange color, which are accumulated in the intima of the vessels (shown by the ar-
row).
27-. Atherosclerosis of artery. (st. hematoxylin and eosin). Using small

magnification find the atherosclerotic plaque in the arterial wall with the damage of
elastic fibers, connective tissue growth and presence of numerous macrophages (xan-
thome cell). There are purple calcium depositions in the intima.
Necrotic debris
(atheromatosis)
Foam cells
Description of stages of connective tissue desorganization

Dystro- Causes Changes in Changes in External Outcome
phy kind ground fibrous changes of the
substance structures organ
Mucoid Hypoxia Depolimeri- Not Not changed Reversible; irreversible,
swelling zation changed transformation into fi-
brinoid swelling
Classification of amyloidosis
Kind of amyloi- Causes of devel- Mechanism of development Outcome
dosis opment
Primary systemic Plasma cell dys- Stimulus - Monoclonal B cell Organ failure.
amyloidosis (AL) crasias proliferation Excess of Igs Primary amyloidosis
and light chains Partial deg- poor prognosis, second-
radation Insoluble AL fibril ary - better outcome
(controllable)
4. Clinical tasks.
1. A patient suffering for a long period of time from bronchiectasis died of uremia.
1. What process in the kidneys was the reason of lethal complication?
2. What is the name of the amyloidosis affected kidney?
2. A patient suffered from rheumatic mitral valve disease. He died of chronic car-
dio-vascular failure. At autopsy, the valve leaflets were thickened, inosculated,
opaque, dense and milky colored.
1. What dystrophy caused the changes in the valve leaflets?
2. What sequential changes (stages of the process) caused this dystrophy in the
valvular endocardium?
3. Give basic characteristics of each stage of the changes.
4. Which stage was reversible?
3. A patient suffered from hypertensive vascular disease and died of myocardium

infarction. The microscopical examination revealed changed arterioles in different
organs. The vascular walls were thickened, their lumens were narrowed, and there
was homogeneous pinkish material in their intima. At autopsy, the kidneys were de-
creased in size with small-grained changes of their surface.
1. What dystrophy occurred in vascular walls?
2. What process preceded this dystrophy?
3. What is the reason for kidneys size decrease and granularity of their surface?
4. What is the process that has developed in the kidneys?
4. A patient suffered from bronchiectasis for a long period of time. During the last
year proteinuria was detected with the level of protein in the urine 10.0 g/l per day.
The blood plasma protein was decreased. The patient had edema. At the end of the
disease hyperasotemia arose, the patient died of kidney failure.
1. What process in kidneys complicated bronchiectasis?
2. In what other organs can this process be found?
3. What is the gross appearance of kidneys?
4. What is the reason for kidney insufficiency?
5. A woman (the confectioner) appealed to a physician for medical aid. She com-
plained of overweight, walking dyspnea, edema of the lower limbs. After course of
treatment (a diet and exercises) the weight came to norm, dyspnea vanished.
1. What is the mechanism of the overweight development in this case?
2. What changes can be found in heart?
3. What is the reason for cardiac failure signs (dyspnea)?
ANSWERS
Number of question with the answer
1 2 3 4
Amyloido- Large lardaceous kid-
1 sis of kidney, later amyloid
neys shrinkage of the kid-
ney
Hyalinosis Mucoid swelling, 1st stage accumulation and redistribution 1st stage mucoid
fibrinoid swelling, of glycosaminoglycans; 2nd stage dis- swelling
hyalinosis truction of collagen fibers, depolymeriza-
2
tion of glycosaminoglycans, imbibition of
groud substance by plasma proteins; 3rd
stage hyalinosis
Hyalinosis Plasmorrhagia Hyalinosis of arterioles leads to hypoxia Primary nephosclero-
and atrophy of some nephrons. There is sis
sclerosis in the place of dead nephrons
3 with the formation of multiple tiny scars
on kidney surface. Unaffected nephrons
undergo hypertrophy and thus jut out the
kidney surface as grey-reddish granules.
Amyloido- Heart, liver, adrenal Large lardaceous kidney, nephosclerosis Amyloid damage of
4 sis of kid- glands, etc. kidneys parenchyma
neys and sclerosis
Simple obe- Mesenchymal dystro- Fat tissue covers the heart in subepicardial
sity phy area and then invades the myocardial
5
stroma causing atrophy myocardial fibers
and sclerosis
5. Self assessment.
1. Cholesterol or cholesterol esters intracellular accumulation occurs in all of the following
processes, EXCEPT:
1. Atherosclerosis
2. Xanthomas
3. Apoptosis
4. Inflammation and necrosis
5. Cholesterosis
2. Cells which can accumulate cholesterol and cholesterol esters in atherosclerotic plaque
are:
1. Macrophages and smooth muscle cells
2. Leucocytes and fibroblasts
3. Lymphocytes and erythrocytes
4. Fibroblasts and leucocytes
5. Erythrocytes and lymphocytes
3. The key role in pathogenesis of familial hypercholesterolemia is played by:
1. VLDL
2. IDL
3. LDL
4. Enzymes
5. Glycogen
4. The cells that accumulate fat in atherosclerotic plaques are called:
1. Fibroblasts
2. Epithelial cells
3. Foam cells
4. Lymphocytes
5. Leukocytes
5. The nephrotic syndrome is characterized by all of the following manifestations,
EXCEPT:
1. Massive proteinuria
2. Hypoalbuminemia
3. Generalized edema
4. Hyperlipidemia and lipiduria
5. Hyperalbuminemia
6. All of the following diseases cause nephrotic syndrome, EXCEPT:
1. Lipoid nephrosis
3. Amyloidosis
4. Obesity
5. Malignant disease
EXCEPT:
2. Hyperalbuminemia
5. Hypoalbuminemia
8. Cholesterol or cholesterol esters intracellular accumulation occurs in all of the follow-
ing processes, EXCEPT:
1. Atherosclerosis
2. Xanthomas
3. Cholesterosis
5. Apoptosis
1. Fibroblasts
2. Epithelial cells
3. Foam cells
4. Lymphocytes
5. Leukocytes
1. LDL
2. IDL
3. VLDL
4. Enzymes
5. Glycogen
11. Cells which can accumulate cholesterol and cholesterol esters in atherosclerotic
plaque are:
12. All of the following diseases cause nephrotic syndrome, EXCEPT:
1. Obesity
3. Amyloidosis
4. Lipoid nephrosis
5. Malignant disease
1. LDL
2. IDL
3. VLDL
4. Enzymes
5. Glycogen
1. Fibroblasts
2. Epithelial cells
3. Foam cells
4. Lymphocytes
5. Leukocytes
EXCEPT:
2. Hypoalbuminemia
5. Hyperalbuminemia
1. Fibroblasts
2. Epithelial cells
3. Foam cells
4. Lymphocytes
5. Leukocytes
17. Cholesterol or cholesterol esters intracellular accumulation occurs in all of the follow-
ing processes, EXCEPT:
1. Atherosclerosis
2. Xanthomas
3. Apoptosis
5. Cholesterosis
EXCEPT:
2. Hyperalbuminemia
5. Hypoalbuminemia
19. Cells which can accumulate cholesterol and cholesterol esters in atherosclerotic
plaque are:
1. LDL
2. IDL
3. VLDL
4. Enzymes
5. Glycogen
Answers
1 3 11 1
2 1 12 1
3 3 13 1
4 3 14 3
5 5 15 5
6 4 16 3
7 2 17 3
8 5 18 2
9 3 19 1
10 1 20 1
Class 3
Theme: MIXED DYSTROPHIES. DISTURBANCES OF
NUCLEOPROTEINS EXCHANGE. MINERAL DYSTROPHIES

1. Definition and classification of mixed dystrophies.
2. Disturbance of chromoproteids exchange.
2.1 Haemoprotein-derived pigments.
a. Ferritin.
b. Hemosiderin.
c. Hematoidin.
d. Hematin
e. Bilirubin.
f. Porphyrins.
2.2. Proteinogenous pigments.
2.3 Lipidogenous pigments.
3. Nucleoproteins metabolism disturbances. Gout, urinary infarction, urolithia-
sis.
4. Mineral dystrophies, their kinds.
4.1. The metabolism of calcium in norm and pathology: the forms and
mechanisms of pathological calcinosis: the causes, the morphological char-
acteristic.
4.2. Disturbance of potassium metabolism.
4.3. Disturbance of copper metabolism (Konovalov-Wilson's disease).
5. Formation of stones: the causes, mechanism of stone formation, consequenc-
es.
MIXED DYSTROPHY is defined as metabolic disturbances occurring in pa-
renchyma and stroma of tissues and organs. The development of mixed dystrophies is
the result of chromoproteins, nucleoproteins and mineral metabolism disorders.
PATHOLOGY OF PIGMENTS
Pigments are colored substances, some of them are normal constituents of or-
ganism whereas others are abnormal and store in tissues and organs only under spe-
cial circumstances.
Pigments are generally classified into two broad categories:
Endogenous pigments, that are normal constituents of cells and tissues;
Exogenous pigments introduced into a body from the environment.
Classification of endogenous pigments
1. Haemoprotein-derived pigments.
2. Proteinogenic (tyrosinogenic) pigments.
3. Lipidogenic (lipid) pigments.
Pigments derived from hemoproteins appear as a result of physiologic break-
down of erythrocytes.
Physiologic pigments:
1. Ferritin is a ferroproteide. It is located in the liver, spleen, bone marrow and
lymph nodes. There are two forms of ferritin: inactive and active (formed due to lack
of oxygen, characterized by vasoparalytic and hypotensive actions). Active ferritin is
adrenalin antagonist). The pathological condition characterized by increasing of ferri-
tin level in blood and tissues is haemosiderosis. Ferritinaemia is a cause of shock ir-
reversibility.
2. Haemosiderin is an iron-containing pigment. Haemosiderin being a poly-
mer of ferritin is identifiable by light microscopy as golden-yellow to brown granular
pigment, in the mononuclear phagocytes of the bone marrow, spleen and liver. He-
mosiderin has ferric iron that can be demonstrated by Prussian blue reaction.
3. Bilirubin is an iron-free pigment.
Pathologic pigments
1. Hematoidin is an iron-free, orange-brown crystal pigment. It is formed ex-
travascularly in the center of hemorrhages or foci of necrosis in anaerobic conditions.
2. Haematin is a brown-black pigment derived from hemoglobin and has 3
types:
Muriatic haematin is formed in gastric erosions and ulcers as the result of in-
teraction between hemoglobin and enzymes with hydrochloric acid of gastric juice.
Hemomelanin is a brown pigment produced by malarial parasites from hemo-
globin; it is taken up by monocytes in the blood and subsequently deposited in the
liver and spleen.
Formalin pigment
3. Porphyrin is a precursor of haem. It is present in blood and urine. Clinical
symptoms are photophobia, erythema, and dermatitis. Spleen, bones, teeth and urine
become dark-red. Porphyria develops when porphyrin metabolism is disturbed. It
may be congenital and acquired. Acquired porphyria is observed in intoxications,
avitaminosis (pellagra), pernicious anemia, and in diseases of the liver.
PATHOLOGY OF HEMOSIDERINS METABOLISM
H A E M OS I DE R OS I S
Haemosiderosis occurs in two situations:
Local haemosiderosis.
It is characterized by local breakdown of red cells in tissues, e.g. in internal
hemorrhage. Mechanism of local haemosiderosis is extravascular hemolysis.
It occurs regularly around areas of bruising and hemorrhage.
In each instance the pigment is localized in cells of the reticuloendothelial
system.
In the lungs haemosiderin-laden macrophages (siderophages) are appropri-
ately referred to as "heart failure cells".
Visceral haemosiderosis (systemic haemosiderosis).
Mechanism of systemic haemosiderosis is intravascular hemolysis.
It is seen in the liver, spleen and sometimes in kidneys in cases of hemolytic
anemia, and in patients requiring repeated blood transfusion. The generalized form of
this condition is also referred to as secondary hemochromatosis.
The pigment imparts a deep brown color to tissues and organs when it is pre-
sent in high concentrations.
It can also occur in patients with chronic ineffective erythropoiesis (such as
thalassemia major).
In hemochromatosis, a genetic disorder, the absorption of iron is virtually
uncontrolled. The system becomes overloaded and iron is deposited as hemosiderin
in many organs, the main ones are:
- Pancreas associated with fibrosis that may destroy islet tissue (diabetes
mellitus).
- Liver usually associated with fibrosis (cirrhosis).
- Skin mainly around sweat glands. Excessive amount of melanin is also de-
posited; hence this condition is sometimes termed bronzed diabetes.
- Heart muscle.
- Mesenteric lymph nodes.
PATHOLOGY OF BILIRUBIN METABOLISM
J A UN DI C E
When the bilirubin content of the serum rises above 34 mmol/l, jaundice ap-
pears.
Types of jaundice
1. Prehepatic jaundice (Hemolytic jaundice) results from excessive break-
down of red blood cell membrane in a variety of conditions, which include:
A genetic membrane defect.
An immune reaction.
Circulation of intravascular toxic substances causing red cell destruction
(snake poison),
Hemolytic (familial) jaundice in spherocytosis,
Sickle cell anemia.
Hemolytic disease of the newborn, Rh incompatibility.
Incompatible blood transfusion.
Infections (malaria, clostridial infection, mycoplasma pneumonia, sepsis)
Leukemia.
In these conditions the excessive amount of pigment does not pass through the
liver for conjugation. The liver's capacity to conjugate it is exceeded, and the level of
unconjugated bilirubin rises in the plasma. It can crystallize out in the tissues and in
the brain, it may cause necrosis. Injury of brain may lead to bilirubin encephalopathy
(kernicterus).
2. Intrahepatic jaundice (Hepatocellular jaundice) results from failure
both of hepatocytes to conjugate bilirubin and of bilirubin to pass through the liver
into the intestine. The amount of both conjugated bilirubin and unconjugated biliru-
bin is increased in blood. The liver has a light yellowish-green color of saffron (saf-
fron liver).
Failure of conjugation may involve:
Hepatocellular jaundice, e.g., viral hepatitis and hypoxic necrosis.
Drug-induced jaundice, e.g., disturbance of glucuronid conjugation.
Intrahepatic cholestasis, e.g., congenital intrahepatic occlusion, tumors, in-
flammation, or cirrhosis.
Mushroom, arsenic, phosphorous poisoning.
3. Posthepatic jaundice (Obstructive jaundice) results from an obstruction
of the passage of conjugated bilirubin from hepatocytes to the intestine. Conjugated
bilirubin is water-soluble and is excreted in the urine. The liver is dark green.
Obstructive jaundice may appear in the following causes:
Stenosis of extrahepatic bile ducts.
Gall stones in the major ducts.
Pancreatic tumor compression.
Fibrosis involving the small intrahepatic ducts; the bile ducts became distend-
ed with conjugated bilirubin, which is reabsorbed.
In the liver, bile pigments may appear:
a) As bile pigment droplets in hepatocytes.
b) As bile impregnations in necrotic areas.
c) As bile lakes (dilated bile capillaries, cholangioles, or bile canaliculi).
d) In Kupffer's cells.
PATHOLOGY OF THE PROTEINOGENIC PIGMENTS
METABOLISM
Melanin is a normal pigment found in the form of fine brown granules in the
skin, choroid of the eye, adrenal medulla, hair, meninges and intestine.
Melanin is a brown-black pigment synthesized by melanocytes from tyrosine
by its oxidation.
After secretion of the pigment, it's taken up by adjacent epidermal cells and
phagocytic melanophores in the underlying dermis.
Ultraviolet radiation stimulates the synthesis of melanin.
Various disorders of melanin pigmentation cause generalized and localized
hyperpigmentation and hypopigmentation.
Focal hyperpigmentation: malignant melanoma, nevus, melanosis coli, lenti-
go. Nevus is a dysontogenetic malformation (hamartoma) consisting of nevus cells.
It's frequently presented at birth and grows slowly during puberty; also it is consid-
ered as a benign tumor.
Malignant melanoma is a highly malignant neoplasm that invades normal tis-
sues early and widely, and that almost invariably terminates in death.
Generalized melanin pigmentations: a) Addison's disease, b) adrenocortical
insufficiency resulting from destruction of the adrenal cortex, c) chloasma observed
during pregnancy, d) chronic arsenical poisoning.
Localised hypopigmentation: a) leucoderma is partial albinism and is an in-
herited disorder; b) vitiligo is hereditary local hypopigmentation of the skin, c) ac-
quired focal hypopigmentation from various causes such as leprosy, healing of
wounds, syphilis, radiation dermatitis, etc.
Albinism is an inherited generalized disorder of melanin metabolism in which
there is a decrease or absence of the pigment in the skin and choroid of the eye. Albi-
nos have blond hair, poor vision and severe photophobia. They are highly sensitive to
sunlight.
Adrenochrome is a pigment of dark brown color. It is situated in the form of
small kernels in the cells of medullar layer of adrenal glands. It can be found in pheo-
chromocytoma.
The pigment of enterochromaffin cells granules is a tryptophan derivative.
The excessive amounts of this pigment are found in tumors of enterochromaffin cells
which are called carcinoid tumors.
PATHOLOGY OF THE LIPIDOGENIC PIGMENTS METABOLISM
Lipopigments are lipofuscin and lipochrome. Lipofuscin is an insoluble lipid
pigment presented in cells of elderly persons and those with malnutrition or a chronic
wasting disease.
It is a brown intracellular pigment found in hepatocytes, myocardial fibers,
and neurons.
Organs containing large amounts of lipofuscin are deep brown; in the heart
and liver, this is referred to as brown atrophy (cells of organs with brown atrophy are
usually decreased in size).
EXOGENOUS PIGMENTS
Inhaled pigments. The most commonly inhaled substances are carbon or coal
dust; others are silica or stone dust, iron or iron oxide, asbestos and various other or-
ganic substances. Anthracosis (i.e. deposition of carbon particles) is seen in almost
every adult lung and generally provokes no reaction of tissue injury.
Ingested pigments. Chronic ingestion of certain metals may produce pigmen-
tation. Argyria is chronic ingestion of silver compounds. Chronic lead poisoning may
produce the characteristic blue lines on teeth. Carotenemia is yellowish-red coloration
of the skin caused by excessive ingestion of carrots.
Injected pigments (tattooing). Pigments like India ink, cinnabar and carbon
are introduced into the dermis in the process of tattooing where the pigment is taken
up by macrophages and lies permanently in the connective tissue.
MINERAL METABOLISM DISTURBANCES
Minerals play an active role in metabolic processes of the human organism.
They are components of structural elements of cells, enzymes, hormones, vitamins,
and pigments.
The most frequent disturbances in medical practice are the metabolism disor-
ders of calcium, copper, potassium, and iron.
Calcium metabolism disturbances
I. Dystrophic calcification. Dystrophic calcification refers to the macroscopic
deposition of calcium salts in injured tissues and does not simply reflect an accumu-
lation of calcium derived from the bodies of dead cells. It is often visible to the naked
eye, and ranges from gritty, sand like grains to firm, rock-hard material. Staining
with H&E demonstrates calcium salts as deeply basophilic, irregular and granular
clumps. For identification of calcium salts we usually use special reaction called sil-
ver impregnation method or Kossa's method. Calcium deposits are stained black.
It may occur in crucial locations, such as:
1. Necrotic tissue, which is not absorbed:
Old caseous lesions of tuberculosis.
Old infarcts.
Old collections of pus.
Dead parasites (echinococci).
Old thrombi.
Dead fetus (lithopedion).
2. Tissues undergoing slow degeneration:
Hyaline areas in simple tumors.
Tissues in old age, especially fibrous tissue, cartilage, in the mitral or aortic
valves after rheumatic fever with formation of mitral or aortic stenosis or as in ather-
osclerotic coronary arteries with narrowing of those vessels.
II. Metastatic calcinosis (calcium metastases) reflects deranged calcium me-
tabolism associated with increased serum calcium concentration (hypercalcemia). It
has a systemic character; its main cause is hypercalcemia, which may be of endocrine
origin in hyperproduction of Parathormone or hypoproduction of Calcitonine. Calci-
um salts precipitate in different organs, more frequently in the lungs, gastric mucosa,
kidneys, myocardium, arterial walls. It may be associated with:
Reduction of calcium excretion from the organism.
Multiple fractures of the bones.
Hyperparathyroidism.
Chronic renal failure.
Multiple myeloma.
Osteomalacia (when the bone becomes soft).
Lesions of the large intestine (the place of Ca excretion).
Vitamin D intoxication.
The outcome is unfavorable, calcium does not resolve.
Copper metabolism disturbance
This appears as Wilson-Konovalov disease (hepatocerebral degeneration,
hepatolenticular degeneration).
It is a hereditary disease in which liver ceruloplasmin production decreases.
Ceruloplasmin is alpha2-globulin and can bind copper in the blood. As a result, cop-
per becomes free from unstable bonds with plasma proteins and sediments in tissues.
Copper accumulates in the liver, brain, kidneys, cornea (in the cornea it
looks like green-brown ring on the margin of the cornea), in the pancreas, testes, etc.
The state is characterized by the development of liver cirrhosis, degenerative
symmetrical changes in the brain in the area of lens nuclei, caudal body, pale globe,
and cortex.
Copper blood plasma amount is decreased but it is in increased in the urine.
There are 3 forms of the disease: hepatic, lenticular, hepatolenticular.
The outcome is unfavorable.
Potassium metabolism disturbances
Increased blood (hyperpotassemia) and tissue potassium amount is observed in
Addison's disease and is associated with the lesion of the adrenal cortex, the hor-
mones of which regulate electrolyte exchange.
Potassium deficiency causes periodic paralysis (the hereditary disease that is
characterized by attacks of weakness and motor paralysis development).
FORMATION OF STONES
Stones or calculi are dense formations freely lying in cavities of organs or in
ducts.
Their shape depends on the organs in which they are formed: round in the
urinary bladder, facet in the gallbladder (their faces are lapped to each other), branch-
ing in the kidneys.
Their surface may be either smooth or rough.
The color depends on their chemical composition: white (phosphates), yellow
(urates), dark brown or green (pigment).
Cross sectionally, they may be crystalloid (radial structure), colloid (stratified
structure) and colloid-crystalloid (radial-stratified).
Their chemical composition is different, i.e. biliary stones may be cholesterol,
pigment, calcium and combined, urinary urates, phosphates, oxalates (calcium oxa-
late), cystin, xantin.
Bronchial calculi consist of mucus inlayed with calcium.
Stones are most frequently formed in the bile ducts and urinary tract in chole-
lithiasis, urolithiasis, in the excretory ducts of the pancreas, salivary glands, bronchi,
crypts of the tonsils, veins (phlebolith), intestine (coprolyth). Both general and local
factors are important for pathogenesis of calculus formation. General factors are the
main ones; they are acquired or hereditary disturbances of metabolism. Local factors
are congestion, inflammation. The immediate mechanism of calculus formation con-
sists of two processes: formation of organic matrix and salt crystallization. Each of
these may be primary.
Compression by a stone may result in necroses in renal pelvis, gallbladder,
bedsores, perforations, inflammation (pyelocystitis, cholecystitis, cholangitis, etc.).
THE DISTURBANCE OF NUCLEOPROTEINS METABOLISM.
Nucleoproteins consist of protein and nucleic acid.
In disturbances of nucleoproteins metabolism and excessive formation of uric
acid, its salts can precipitate in tissues. This process is observed in podagra, urolithia-
sis and uric acid infarction of kidneys.
Podagra (gout) is characterized by periodic precipitation of sodium salt of uric
acid in joints accompanied by painful attacks. An increase in uric acid salts content in
blood (hyperuricemia) and in urine (hyperuricuria) is found in patients. Salts usually
accumulate in synovia and cartilages of foots and small joints of hands, talocrural and
knee joints, in tendons and articular bags, in the cartilage of auricles. There is necro-
sis of tissues in which salts precipitate in the form of crystals or amorphous substanc-
es. An inflammatory reaction with the appearance of giant cells develops around salts
depositions and necrotic foci. Podagric tophus develops when there is an increase in
salt deposition and connective tissue growth in periarticular regions and adjacent tis-
sues. It arises in auricles and other parts of the body leading to the deformation of
joints.
Changes in kidneys. There is accumulation of uric acid and sodium salt of uric
acid in renal tubules and collecting tubes with the obturation of their lumens and de-
velopment of secondary inflammatory and atrophic changes (gouty kidneys) in po-
dagra.
The development of podagra is mainly caused by congenital disturbances of me-
tabolism (primary gout), thus the role of dietary habits and over-use of animal pro-
teins is great. Less often gout is the complication of other diseases (secondary gout),
such, as nephrocirrhosis, leukaemias, etc.
Urolithiasis is caused, first of all, by the disturbances of purine metabolism i.e. it
can be the manifestation of so-called urine acid diathesis. Thus urates are formed in
kidneys and urinary tracts.
Uric acid infarct occurs in newborns of two days old and above. It is manifested
by depositions of amorphous substances of sodium salt of uric acid and ammonium in
renal tubules and collecting tubes. The cause of uric acid infarction is intensive me-
tabolism in the first days of newborn life. It reflects an adaptative reaction of kidneys
to the new conditions of existence.
3. Class work.

107, 108 Stones of kidney and kidney pelvis. Determine the chemical
compound of stones according to their form and type. Define the value of stone for-
mation for a kidney.
133 Stones of the gallbladder. Pay attention to the form and the size of
stones, their color and structure.
141, 143, 176 Atherosclerosis of the aorta. Name the kind of cal-
cinosis in aortic atherosclerosis.

43 Brown lung indurations (hematoxylin and eosin st. A, Prussian blue
reaction (Perls st.) B). Pay attention to the status of vessels in interalveolar septum
(II barrier). Find grains of brown pigment in Figure A and blue pigment in Figure B.
Note its localization and arrangement in lung tissue. Characterize the status of alveo-
lar cavities. What is the name of cells that contain hemoglobin pigment and are local-
ized in the lumen of alveolus and small bronchia?
A B
32 Liver in mechanical jaundice. (st. hematoxylin and eosin). Find dilat-

ed bile capillaries full of bile. Pay attention to cholestasis (stasis of bile in hepato-
cytes).
35 Skin in Addison disease. (st. hematoxylin and eosin). Pay attention to
the pigment arrangement in epithelial basal layer (shown by the arrow). In what dis-
eases does this syndrome develop? Draw.
7 Brown atrophy of the myocardium. (st. hematoxylin and eosin). Study

the micropreparation. Pay attention to the reduction of the fiber sizes, presence of a
yellowish brown pigment in them. Note the localization of pigment grains in the
muscular fibers and the kind of pigment. What diseases are characterized by these
changes?
34 Brain in malarial coma. (st. hematoxylin and eosin). Using large
magnification, find dark brown grains of a pigment in the specimen. In what organs is
deposition of this pigment observed?
29 Necrosis of the skeletal muscle with ossification. (st. hematoxylin

and eosin). Draw. Note the causes and the mechanism of ossification.
70 Primary effect at the healing stage. (st. hematoxylin and eosin). Find
the zone of ossification of caseous necrosis (shown by the arrow). What is the mech-
anism of ossification?
36 Hemosiderosis of spleen. (Perls stain). Find accumulations of blue

grains (haemosiderin) in reticuloendothelial cells.
Classification of haemoglobinogenic pigments.
Name of pigment Physiologic Pathologic Iron-containing pig- Iron-free

Pigment pigment ments pigments
Ferritin + - + -
Pathological calcinoses
Form of Causes Localization of Outcomes

calcinosis lesions
Metastatic Reduction of calcium excretion from the organism, Lungs, gastric Unfavorable
calcinosis multiple fractures of the bones, hyperparathyroid- mucosa, kidneys,
ism, chronic renal failure, multiple myeloma, os- myocardium,
teomalacia (when the bone becomes soft), lesions aorta
of the large intestine (the place of Ca excretion),
vitamin D intoxication
Make the scheme of biliary tract and explain the cases when the development
of obstructive (mechanical) jaundice is possible.
Name the methods of RNA and DNA revelation in cells and tissues, and meth-
ods of mineral substances revealing.
4. Clinical tasks.
1. A patient who suffered from leucosis developed anemia, icteric skin and sclera
after repeated blood transfusions. Death occurred from cerebral hemorrhage. At au-
topsy, the enlarged liver and spleen, the bone marrow, were brown.
1. What pigment caused brown colour of the organs?
2. What is the name of the pathological process that caused these pathological
changes in the organs?
3. What is the mechanism of its development?
4. What is the type of jaundice in this clinical case?
2. A patient suffering from lung carcinoma with multiple metastases developed dark
brown colour of the skin, severe weakness, adynamia, and hypotension.
1. Metastatic damage of what organ caused such clinical findings?
2. What is the name of the diagnosed skin changes?
3. Accumulation of what pigment caused dark brown colour of the skin?
4. Which cells contain this pigment?
5. What is the mechanism of excessive production of this pigment in Addissons
disease?
3. A patient who suffered from carcinoma of the esophagus died of cachexia. At au-
topsy, the heart was decreased in size, the myocardium was brown.
1. What is the name of the changes found in the heart?
2. Where else may these changes be found?
3. What pigment caused brown colour of the organs?
4. What is the group name of this pigment?
4. A woman suffering from cramping pains in joints of her hands and feet had hype-
ruricemy. A biopsy of the joint was made.
1. What is the womans disease?
2. What microscopical changes may be found in the biopsy of the joint?
3. What other organ is frequently damaged in this disease?
5. A patient who suffered from parathyroid gland tumor had high hypercalcemia,
destructive changes in bones. He died of pneumonia. Microscopic examination re-
vealed multiple metastatic foci of calcification in myocardium and kidneys.
1. What is the type of calcinosis in this case?
2. What organelles of myocardial fiber and nephrocyte are the matrices for cal-
cium deposition?
3. In which other organs may this type of calcinosis be revealed?
6. A woman suffering from cholelithiasis presents to the emergency department

with pain in the right area below the ribs and jaundice.
1. Where can be the stone localized in this case?
2. What kind of jaundice occurred in the patient?
3. What chemical compound may be found in stones in the biliary tract?
7. A patient with purine metabolism disturbance has intermittent pain in lumbar ar-
ea. Examination reveals enlargement and tenderness of right kidney. X-ray examina-
tion shows a concrement in the outlet of kidney pelvis.
1. What is the diagnosis?
2. What is the chemical composition of the stone?
3. What complications may be caused by the concrement?
ANSWERS
1 1 2 3 4 5
Haemo- Generalized hae- Intravascular Prehepatic
siderin mosiderosis haemolysis jaundice
2 Metastases Generalized hyper- Melanin Melanocytes, Decrease of adrenalin
of carci- pigmentation (Ad- melanophores, synthesis, activation of
noma in disons disease) dendritic cells, ACTH synthesis that
the adrenal keratinocytes has melanin stimulating
glands action
3 Brown Liver, skeletal Lipofuscin Lipidogenic
atrophy of muscles pigments
the heart
4 Gout Deposition of sodi- Kidneys
(podagra) um urate, necrosis,
inflammation,
growth of connec-
tive tissue
5 Metastatic Mitochondrions, Lungs, artetial
lysosomes walls, gastric
mucosa
6 Ductus Posthepatic (me- Cholesterol,
choledoch chanical, obstruc- pigment, calci-
us tive) um and com-
bined
7 Urinary Urates Hydronephrosis,
stone dis- inflammation
ease
5. Self assessment.
1. All of the following abnormal clinical manifestations are correctly paired with the ap-
propriate compound or pigment deposits, EXCEPT:
1. CCl4 poisoning fat
2. Hemolytic anemia bilirubin
3. Idiopathic hemosiderosis hemosiderin
4. Vitiligo melanin
5. Atrophy of hepatic cells lipofuscin
2. The main morphological features of pulmonary hemosiderosis include all of the follow-
ing, EXCEPT:
1. Prominent degeneration
2. Hypertrophy of septal cells
3. Shedding of alveolar epithelial cells
4. Hyperplasia of alveolar epithelial cells
5. Marked alveolar capillary congestion
3. Lipofuscin has all of the following features, EXCEPT:
1. Aging pigment
2. Most often seen in kidney
3. Yellow-brown
4. Noninjurious to the cells or their function
5. Endogenous pigment
4. Jaundice occurs in all of the following pathologic processes, EXCEPT:
1. Increased hepatocellular excretion
2. Excessive production of bilirubin
3. Reduced hepatocyte uptake
4. Impaired conjugation of bilirubin
5. Impaired bile flow
5. The causes of metastatic calcification are all of the following, EXCEPT:
2. Increased secretion of parathyroid hormone
3. Destruction of bone tissue
4. Vitamin D-related disorders
5. Renal failure
6. Specific stain for iron is called:
1. Hematoxylin and eosin
2. Sudan III
3. Prussian blue
4. Congo red
5. PAS-reaction
7. The color of hemosiderin granules stained with Prussian blue reaction is:
1. Yellow
2. Brown
3. Orange-red
4. Pink
5. Blue-black
8. Lipofuscin pigment granules in cells result from:
1. Hemosiderosis
2. Accumulation of protein in cytoplasm
3. Accumulation of lipids in cytoplasm
4. Cellular swelling
5. Intracellular lipid peroxidation
9. Unconjugated hyperbilirubinemia occurs in all of the following pathologic processes,
EXCEPT:
1. Excessive production of bilirubin
2. Reduced hepatocyte uptake
3. Decreased hepatocellular excretion
4. Impaired conjugation
5. Hepatocytes injury in viral hepatitis B
10. Metastatic calcification may occur in all of the following organs, EXCEPT:
1. Stomach (gastric mucosa)
2. Kidneys
3. Lungs
4. Liver
5. Heart, systemic arteries and pulmonary veins
11. Hemosiderin has all of the following features, EXCEPT:
1. Hemoglobin-derived
2. Golden yellow-to-brown
3. Granular or crystalline
4. Synthesized by enzyme tyrosinase
5. Is aggregated form of ferritin
12. Hemosiderosis is seen in all pathologic processes, EXCEPT:
1. Inflammation
2. Hereditary increased absorption of dietary iron
3. Impaired use of iron
4. Hemolytic anemia
5. Malaria
13. Lipofuscin granules in cells are seen in:
1. Necrosis
2. Denervation atrophy
3. Brown atrophy
4. Atrophy from pressure
5. Atrophy from diminished blood supply
14. Which of the following sites is an example of metastatic calcification?
1. The kidney in nephrocalcinosis
2. The mitral valve in mitral stenosis of rheumatic organ
3. The left anterior ascending coronary artery affected by atheromatous plaques
4. The lung involved by metastatic carcinoma
5. The lung in areas of old tuberculosis foci
15. Deficiency of vitamin D in adults leads to:
1. Osteosclerosis
2. Osteomyelitis
3. Osteomalatia
4. Osteonecrosis
5. Osteoporosis
16. Hemosiderin in the lungs is accumulated in:
1. Leukocytes
2. Lymphocytes
3. Macrophages
4. Fibroblasts
5.Erythrocytes
17. Morphologic changes in genetic hemochromatosis are characterized by all of the fol-
lowing, EXCEPT:
1. Metastatic calcification of many organs
2. Deposition of hemosiderin in many organs
3. Deposition of hemosiderin in the skin
4. Liver cirrhosis
5. Pancreatic fibrosis
18. Heart and liver of a patient with cancer cachexia are macroscopically seen as:
1. Diminished and brown
2. Diminished and yellow
3. Enlarged and brown
4. Enlarged and yellow
5. Unchanged
19. Point out the post tuberculosis lung lesion:
1. Granuloma
2. Cavity
3. Fibrocalcific scar
4. Caseation in lymph node
5. Caseation in lung
20. The pathognomonic hallmark of gout is:
1. Fibrotic scar
2. Granuloma
3. Cyst
4. Gumma
5. Tophus
ANSWERS
1 4 11 4
2 2 12 1
3 2 13 3
4 1 14 1
5 1 15 3
6 3 16 3
7 5 17 1
8 5 18 1
9 3 19 3
10 4 20 5
Class 4
Theme: NECROSIS. GENERAL DEATH

1. The definition of necrosis.
2. Causes, mechanism of development and morphological characteristic of ne-
crosis.
3. Stages of necrosis and their morphological characteristic.
4. Classification of necrosis according to the causes and mechanism of the
pathogenic factor action.
5. Clinicomorphological forms of necrosis and their characteristics.
6. Effects of necrosis and its outcomes.
7. Definition of apoptosis and its morphological characteristic.
8. Death: definition, causes, classification.
2. Fill in the table:

Classification of necrosis.
According to the mechanism of According to the causes
pathological factor action
3. The theoretical part.

IRREVERSIBLE CELL INJURY (CELL DEATH).
Cell death is a state of irreversible injury. It may occur in the living body as a
local change (i.e. autolysis, necrosis and apoptosis), or result in end of the life (so-
matic death).
Autolysis (self-digestion) is disintegration of the cell by its own hydrolytic
enzymes liberated from lysosomes. Autolysis can occur in the living body when it is
surrounded by inflammatory reaction (vital reaction), or may occur as postmortem
change in which there is complete absence of surrounding inflammatory response.
Autolysis is rapid in some tissues rich in hydrolytic enzymes such as in the pancreas,
and gastric mucosa, intermediate in tissues like the heart, liver and kidney, and slow
in fibrous tissue.
NECROSIS
Necrosis is a cellular death in the living body. Necrosis is defined as focal
death along with degradation of tissue by hydrolytic enzymes liberated by cells. It is
invariably accompanied by inflammatory reaction.
Two essential changes bring about irreversible cell injury in necrosis cell di-
gestion by lytic enzymes and denaturation of proteins.
Nuclear changes. The irreversibly damaged nuclei are characterized by one
of the following three features:
1. At first nucleus shrinks and becomes dense. This process is called kary-
opycnosis.
2. After that karyorrhexis develops. This process is characterized by rupture
of nuclear membrane and fragmentation of the nucleus. Nucleus is decomposed into
small granules.
3. Also karyolysis may develop, when the nucleus dissolves.
At electron microscopic level, in addition to the above nuclear changes, disor-
ganization and disintegration of the cytoplasmic organelles and severe damage of the
plasma membrane are seen.
In the cytoplasm, protein denaturation and coagulation or hydration and col-
liquation take place. Plasmorrhexis is characterized by decomposition of cytoplasm
into clumps due to coagulation. Then plasmolysis takes place. Plasmolysis is hydro-
lytic fusion of cytoplasm. Sometimes we can observe vacuolization and calcification
in the cytoplasm.
Stages of necrosis (the morphogenesis):
1. Paranecrosis reversible changes; as a rule, reversible degeneration.
2. Necrobiosis irreversible degenerative changes.
3. Death of cell.
4. Autolysis is the enzymatic digestion of the dead cell due to effect of catalyt-
ic enzymes derived from lysosomes.
T Y PES OF N EC RO S I S
According to the mechanisms of pathological factor action:
1. Direct (from influence of mechanical, physical, chemical, and toxic factors).
2. Indirect (vascular and neurogenous).
According to the cause:
1. Traumatic.
2. Toxic.
3. Trophoneurotic.
4. Allergic.
5. Vascular or ischemic.
According to the morphological features:
1. Coagulative necrosis is associated with inhibition of lytic enzymes. Foci of
coagulative necrosis in the early stage are pale, firm, and slightly swollen. With pro-
gression they become more yellowish, softer, and shrunken. The cells are not lysed;
thus, their outlines are relatively preserved. Nuclei disappear and the acidified cyto-
plasm becomes eosinophilic. For instance, the Waxy (Zenker's) necrosis of muscle
may occur at typhoid fever.
The subtypes of coagulative necrosis are the following:
1.1. Caseous necrosis has features of both coagulative and liquefactive necro-
sis. Typically, it occurs in the center of tuberculous granulomas, which contain a
white or yellow "cheesy" material (Latin word caseum means cheese) that accounts
for the name of this lesion. Histologically, the outlines of necrotic cells are not pre-
served, but the tissue has not been liquefied either. The remnants of the cells appear
as finely granular, amorphous material.
1.2. Fibrinoid necrosis is characterized by deposition of fibrin-like material,
which has the staining properties of fibrin. It is encountered in various examples of
immunologic tissue injury, arterioles in hypertension, peptic ulcer etc. Histologically,
fibrinoid necrosis is identified by brightly eosinophilic, hyaline like deposition in the
vascular wall or on the luminal surface of a peptic ulcer.
2. Liquefactive (colliquative) necrosis is marked by dissolution of tissue due
to enzymatic lysis of dead cells. Typically, it takes place in the brain when autocata-
lytic enzymes are released from dead cells. Liquefactive necrosis occurs also in puru-
lent inflammation foci due to the hydrolytic action of polymorphonuclear leucocytes
in pus. Liquefied tissue is soft, diffluent and composed of disintegrated cells and flu-
id.
3. Gangrene develops in organs and tissues having contact with environment.
The most frequent example of gangrene is the gangrene of lower extremities, uterus,
lungs etc. There are 3 main forms of gangrene dry, wet and gas gangrene. The con-
trasting features of two main forms of gangrene are summarized in the Table 1. Pres-
sure sore (bedsore) is a kind of gangrene; it is defined as necrosis of superficial parts
of a body under pressure. According to the cause bedsore is the trophneurotic type of
necrosis.
Sequester is a fragment of dead tissue, that doesnt undergo autolysis and re-
placement by connective tissue and that is localized among alive tissue.
4. Infarction is vascular or ischemic necrosis.
5. Fat necrosis is encountered in adipose tissue contiguous to the pancreas and
more rarely at distant sites and is a result of leakage of lipase after acute injury to
pancreatic acinar tissue, most commonly from obstruction of pancreatic ducts. Gross-
ly, fat necrosis appears as firm, yellow-white deposits in peripancreatic and mesenter-
ic adipose tissue. Histologically, necrotic fat cells are distinguishable as pale outlines,
and their cytoplasm is filled with an amorphous-appearing, faintly basophilic material
(soap).
O U T C O MES OF N EC R OS I S
Regeneration of tissues the replacement of the dead tissue with a new one.
Encapsulation the formation of the connective tissue capsule around necrot-
ic area.
Organization the replacement of the dead tissue with connective tissue.
Petrification the replacement of the dead tissue with calcium salts.
Incrustation the replacement of the dead tissue with any other salt except
calcium.
Ossification the formation of the bone tissue in the necrotic area.
Hyaline change the appearance of the hyaline-like substance in the necrotic
area.
Suppuration or purulent fusion of necrotic tissues.
Sequestration formation of sequester.
Mutilation spontaneous tearing away of the dead tissue.
Cyst formation.
APOPTOSIS
Apoptosis is a programmed (physiological) death of a cell in the living body.
Morphologic features of apoptosis:
1. Cell shrinkage;
2. Chromatin condensation;
3. Formation of cytoplasmic blebs and apoptotic bodies;
4. Phagocytosis of apoptotic cells or bodies.
Histologically, in tissues stained with hematoxylin and eosin, apoptosis in-
volves single cells or small clusters of cells.
The apoptotic cell appears as a round or oval mass of intensely eosinophilic
cytoplasm with dense nuclear chromatin fragments.
Because the cell shrinkage and formation of the apoptotic bodies are rapid,
and the fragments are quickly phagocytized, degraded, or extruded into the lumen,
considerable apoptosis may occur in tissue before it becomes apparent in histological
sections. In addition, apoptosis in contrast to necrosis does not induce inflamma-
tion.
The contrasting features of apoptosis and necrosis are summarized in the Ta-
ble 2.
T A BL E 1 . C ON T R AS T I N G FE A T U R ES O F T WO M A I N F O RMS OF
G A N GR EN E
FEATURE DRYGANGRENE WET GANGRENE
Site Common in limbs More common in bowel
Mechanisms Arterial occlusion More common in venous obstruc-
tion, less often in arterial occlu-
sion
Macroscopy Organ is dry, shrunken and black Part is moist, soft, swollen, rotten
and dark
Putrefaction Limited due to very little blood Marked due to stuffing of organ
supply with blood
Line of demar- Present at the junction between No clear line of demarcation
cation healthy and gangrenous part
Bacteria Bacteria fail to survive Numerous present
Prognosis Generally better due to a little sep- Generally poor due to profound
ticemia toxemia
T A BL E 2 . C ON T R AS T I N G F EA T U RES O F AP O P T OS I S AN D
N EC R OS I S
FEATURE APOPTOSIS NECROSIS
1. Defini- Programmed and coordinated cell Cell death along with degradation
tion death of tissue by hydrolytic enzymes
2 Causative Physiologic and pathologic pro- Hypoxia, toxins
agents cesses
3. Mor- No Inflammatory reaction Inflammatory reaction is always
phology present
Death of single cells Death of many adjacent cells
Cell shrinkage Cell swelling initially
Cytoplasmic blebs on membrane Membrane disruption
Apoptotic bodies Damaged organelles
Chromatin condensation Nuclear disruption
Phagocytosis of apoptotic bodies by Phagocytosis of cell debris by mac-
macrophages rophages
4. Molecu- Lysosomes and other organelles Lysosomal breakdown with libera-
lar changes intact tion of hydrolytic enzymes and on-
cossuppressor genes
DEATH, SIGNS OF DEATH, POSTMORTEM CHANGES

Death is the expression of irreversible stoppage of the vital activity of organ-
ism. After death a man turns into a dead body or corpse (cadaver).
There are natural (physiologic), violent death and death due to diseases.
Natural death develops in senile persons as a result of physiologic wear of or-
ganism.
Violent death is a result of murders, suicides, traumas and accidents.
Death due to diseases is a result of incompatibility of life with changes that
are provoked by pathological (unhealthy) processes.
There is clinical and biological death:
1. Clinical death is characterized by the stoppage (stopping) of breathing and
blood circulation, which are reversible during some minutes (the time of outliving of
the brain cortex). Agony precedes clinical death and is the result of uncoordinated
actions of homeostatic systems during terminal period (arrhythmia, paralysis of
sphincters, convulsions and pulmonary edema).
2. Biological death is irreversible changes of vital activity of organism and be-
ginning of autolytic processes. The central nervous system dies in the first 5-6
minutes. In other organs and tissues this process takes some hours or even days.
Soon after biological death a number of signs of death and postmortem changes
appear. They are the following:
cooling of the dead body (algor mortis) develops as the result of stoppage of
warmth production in the body and equalization of temperature of the dead body with
the environment;
cadaveric rigidity (rigor mortis) is manifested as condensation of voluntary
and involuntary muscles because of disappearance of adenosine triphosphate and ac-
cumulation of lactic acid in them. Usually it develops in 2-5 hours after death, in-
volves all muscles of the body at the end of the first day, is kept during 2-3 days and
then disappears;
cadaveric drying appears because of evaporation of moisture from the surface
of the body. It may be localized or generalized (mummification). The dimness of cor-
nea and appearance of dark-brown patches on sclera result from this process;
redistribution of blood in a corpse results in full filling of veins with blood,
but arteries remain almost empty. The postmortem coagulation of blood in veins and
cavities of the right part of the heart takes place. However in the cases of death be-
cause of asphyxia the blood does not coagulate (asphyxia of newborns);
cadaveric spots appear because of redistribution of blood in the corpse and
depend on its position. The blood flows down into the veins of the lower parts of
body and accumulates there. That's why cadaveric hypostases appear in 3-6 hour after
death;
putrefaction of a corpse is provided by processes of autolysis and rotting of
the corpse. Postmortem autolysis appears earlier and is more expressed in glandular
organs the cells of which are rich in proteolytic enzymes (liver, pancreas, stomach).
Putrefactive processes follow quickly the postmortem autolysis because of putrefac-
tive bacteria propagating. Putrefaction intensifies postmortem autolysis, leading to
fusion of tissues that begin to have a dirty-green color and exhale characteristic putrid
smell. Quickness of corpse's autolysis and putrefaction depends on the temperature of
the environment.
4. Class work.
246 Ischemic infarct of the spleen. There is a wedge shape infarct under
the capsule of the spleen. Infarct is white, firm, clearly circumscribed. There is deposi-
tion of fibrin on the capsule.
274 Ischemic infarct of the brain. Pay attention to irregular focus in the
brain matter which consists of porridge-like grey masses.
276 Cyst of the brain. There is a cavity with smooth surface in the brain
matter. Describe the localization of the cyst, its form and size, and explain the mecha-
nism of occurrence.
348 Gangrene of the foot. Dead area is black, dry with a demarcation in-
flammatory zone. Explain the mechanism of occurrence.
47 Intestine gangrene. The small intestine loops are black-red, flabby,
swollen; their serous membrane is covered by fibrin.
69 Necrosis of the skeletal muscles in typhoid fever. Dead foci are dry,
firm, grey-yellow, resembles a wax (waxy necrosis).
191 Pulmonary infarct. Wedge shaped necrotized tissue is dark-red and
firm.

3 Necrosis of skeletal muscles in abdominal typhus. (st. hematoxylin and
eosin). Using small magnification find layers of the muscular fibers which have un-
dergone necrosis. Define the type of necrosis. Using large magnification, study micro-
scopic signs of necrosis. Draw.
5 Caseous necrosis of lymph node. (st. hematoxylin and eosin). Using
small magnification, pay attention to wide area of necrosis, surrounded by inflamma-
tory infiltrate. In the inflammatory zone there are a lot of Pirogov-Langhans` cells.
2 Necrotic nephrosis (necrosis of kidney epithelium). (st. hematoxylin

and eosin). Define the status of the epithelium of proximal convoluted tubules. Using
large magnification, determine the form of nucleus destruction and cytoplasm status.
Note intact nuclei in nephrones vascular loops and distal parts of canaliculli. Draw.
109-a. Myocardium infarct. (st. hematoxylin and eosin). Using small
magnification, find 3 zones: ) necrosis; b) demarcation zone; c) viable tissue. In the
necrotic zone, pay attention to the homogeneous condition of fibers. In the demarca-
tion zone, pay attention to the status of vessels and determine cellular elements com-
position. Draw.
Demarcative
inflammation
Necrosis

Microscopic signs of necrosis
Cells Intercellular matter
Nucleus cytoplasm matrix Fibers
karyopycnosis, karyor- coagulation of cyto- swelling and collagen fibers imbibition
rhexis, karyolysis plasm, plasmorrhexis, lysis by plasma proteins, fragmen-
plasmolysis tation, lysis;
elastic fibers - swelling, frag-
mentation, elastolysis;
reticular fibers stay in ne-
crosis for a long time, frag-
mentation, breakdown
Clinical-morphological forms of necrosis

Necrosis Morphological characteristic Outcomes
form
Coagulative Foci of CN in the early stage are pale, firm, and slightly swol- Sclerosis, calcinosis,
necrosis (CN) len. With progression, they become more yellowish, softer, putrefaction.
and shrunken. The necrotized cells are swollen and appear
more eosinophilic than the normal. Cell digestion and lique-
faction fail to occur.
5. Clinical tasks.
1. A 67-year-old woman suffering from mesenterial arteries atherosclerosis for a

long period of time was admitted to a surgical department with symptoms of acute
abdomen. On laparotomy, small intestine loops are necrotized
1. What is the clinicomorphological form of the revealed necrosis in small intes-
tine?
2. Characterize the gross appearance of this bowel.
3. What is the most likely cause of the necrosis?
4. What is the role of intestinal flora in the development of this form of necrosis?
2. After the resection of large tumor of retroperitoneal space a patient developed
acute kidney failure. During the operation massive bleeding and blood pressure fall
occurred.
1. What process occurred in the kidneys?
2. What is the etiological form of this necrosis?
3. What is the form of necrosis according to mechanism of pathological factor
action?
4. In what structures of kidneys have necrotic changes occurred?
3. A 71-year-old patient suffering from atherosclerosis has a pain in his left foot. He
did not appeal to a physician. On physical examination, his foot is increased in size,
tissues are flabby, black, and the skin is macerated. Line of demarcation is not clear.
1. What clinicomorphological form of necrosis has occurred?
2. What are the most likely causes of the necrosis?
3. What is the cause of black colour of the foot?
4. What is the form of necrosis according to the mechanism of pathological fac-
tor action?
4. A patient had a transmural myocardial infarction of the anterior wall of left ven-
tricle. Later he began to complain of pain in lumbar area and the development of he-
maturia. In two days he rapidly developed right side hemiplegia, speech disorders.
The patient died of progressing brain edema.
1. What changes were revealed in the kidneys and brain at autopsy?
2. What is the most likely cause of these changes?
3. What is the colour and shape of myocardial infarction?
4. What are the favorable outcomes of the changes in the kidneys and the brain?
5. A 20-year-old patient with tetraplegia caused by spinal cord trauma has shapeless
dark brown necroses with ulceration in the area of sacral bone and spinous processes
of the spinal column.
1. What is the name of these necroses?
2. What is the clinicomorphological form of these necroses?
3. What is the etiologic form of these necroses?
ANSWERS
1 1 2 3 4
Wet gangrene Intestinal loops are flabby, Thrombosis of su- The development of wet
intestinal wall is swollen, perior mesenteric gangrene
edematous, crimson black artery
colour; there is a fibrin on
the serous membrane
2 Necrotic ne- Vascular Indirect In the epithelium of
phrosis proximal and distal con-
voluted tubules
3 Wet gangrene Thrombosis or thromboem- The accumulation Indirect
bolism of lower limbs arter- of sulfureous iron
ies
4 Infarction Thromboembolism from the Pale with hemor- In kidneys: organization

left myocardium ventricle rhagic crown, of necrosis with the for-
shapeless mation of connective
tissue scar; in brain: cyst
formation in the place of
necrosis
5 Bedsores Gangrene Trophoneurotic
6. Self assessment.
1. All the following features characterize reversible cell injury, EXCEPT:
1. Blebs
2. Endoplasmic reticulum swelling
3. Dispersion of ribosomes
4. Myelin figures
5. Autophagy
2. One of the following variants of necrosis can be found in tuberculosis:
1. Caseous necrosis
2. Gangrenous necrosis
3. Liquefactive necrosis
4. Fat necrosis
5. Fibrinoid necrosis
3. Ischemic injury in the central nervous system results in:
2. Coagulative necrosis
3. Caseous necrosis
5. Fat necrosis
4. Apoptotic body is characterized by all of the following, EXCEPT:
1. Eosinophilic cytoplasm
2. Tightly packed organelles
3. Presence of nuclear fragments
4. Absence of nuclear fragments
5. Protein droplets in cytoplasm
5. The tubular epithelial cells in acute tubular necrosis include all of the following patho-
logic features, EXCEPT:
1. Karyolysis
2. Plasmolysis
3. Plasmorrhaxis
4. Plasmocoagulation
5. Mitosis
6. All the following features characterize irreversible cell injury, EXCEPT:
1. Nucleous pyknosis
2. Karyolysis
3. Karyorrhaxis
4. Endoplasmic reticulum swelling
5. Mitochondrial swelling
7. One of the following variants of necrosis is associated with acute pancreatitis:
3. Caseous necrosis
5. Fat necrosis
8. One of the following variants of necrosis can be found in wet gangrene:
3. Caseous necrosis
5. Fat necrosis
9. Apoptotic cell is characterized by all of the following histological features, EXCEPT:
1. Round form
2. Oval form
3. Eosinophilic cytoplasm
4. Basophilic cytoplasm
5. Dense nuclear chromatin fragments
10. All the following features distinguish apoptosis from necrosis, EXCEPT:
1. Absence of inflammation nearby the injured cells
2. Fragmentation of nuclear chromatin only
3. Formation of apoptotic bodies
4. Affection of the separate cells or clusters of cells
5. Presence of inflammation nearby the injured cells
11. Coagulative necrosis is characterized by which of the following pathologic features.
1. Denaturation of cytoplasmic proteins
2. Karyorrhaxis
3. Karyopiknosis
4. Breakdown of cell organelles
5. Lipid deposition
12. One of the following variants of necrosis is associated with syphilis:
3. Caseous necrosis
5. Fat necrosis
13. One of the following variants of necrosis can be found in gangrene of lower extremi-
ties:
3. Caseous necrosis
5. Fat necrosis
14. Borderline inflammation results from:
1. Necrosis
2. Apoptosis
3. Lipofuscinosis
4. All of these
5. None of these
15. The correct definition of autolysis:
1. Changes induced by fixatives used in histopathologic tissue preparation
2. Tissue degradation by intracellular enzymes
3. Ischemic necrosis resulting from arterial occlusion by fibrin clots
4. Ballooning of cell cytoplasm from lipid accumulation
5. Loss of tissue architecture
16. Digestion of the cell by lysosome enzymes of immigrant leukocytes is termed:
1. Autolysis
2. Apoptosis
3. Heterolysis
4. Inflammation
5. Metaplasia
17. One of the following variants of necrosis can be found in myocardial infarction:
3. Caseous necrosis
5. Fat necrosis
18. Apoptosis is characterized by all of the following pathologic features, EXCEPT:
1. Nuclear chromatin condensation
2. Nuclear fragmentation
3. Cytoplasmic budding
4. Organelles swelling
5. Phagocytosis of the apoptotic bodies
19. Apoptotic cell is characterized by all of the following histological features, EXCEPT:
1. Protein cleavage
2. Protein cross-linking
3. DNA synthesis
4. DNA breakdown
5. Expression of adhesive glycoproteins
20. Each type of necrosis is correctly described, EXCEPT:
1. Coagulation loss of tissue architecture
2. Liquefaction enzymatic softening and disruption of devitalized tissue
3. Caseous-eosinophilic, amorphous appearance
4. Fibrinoid deposition of fibrin-like material in arterial walls
5. Autolysis tissue degradation by intracellular enzymes
ANSWERS
1 4 11 5
2 1 12 3
3 1 13 1
4 5 14 1
5 5 15 2
6 4 16 3
7 5 17 1
8 2 18 4
9 4 19 3
10 5 20 1
Class 5
Theme: Arterial and venous hyperemia. Ischemia. Blood stasis.
Bleeding, haemorrhage, plasmorrhagia

1. Hyperemia. Arterial hyperemia: causes, kinds, mechanisms of development,
morphology.
2. Venous hyperemia: local and generalized, acute and chronic, changes in
organs, outcomes.
3. Chronic venous congestion: changes in organs (lungs, liver, spleen, kidney,
skin, mucous coats). Morphogenesis of stagnant sclerosis: changes in lungs,
liver.
4. Ischemia: causes, kinds, morphology, outcomes.
5. Stasis: causes, kinds, mechanisms of development, morphology, outcomes.
Prestasis, sludge phenomena.
6. External and internal bleeding and haemorrhage: causes, kinds, morphology,
outcomes, effects.
7. Plasmorrhagia: causes, mechanisms of development, morphology.
H E MO D Y N AMI C DI S T UR B A NC E S
These are considered under two broad headings:
Disturbances in the volume of the circulating blood. These include hyperemia
and congestion, hemorrhage and shock
Circulatory disturbances of obstructive nature.
These are thrombosis, embolism, ischemia and infarction.
HYPEREMIA AND CONGESTION
Hyperemia and congestion are the terms used for increased volume of blood
within dilated vessels of an organ or tissue; the increased volume from arterial and
arteriolar dilatation being referred to as hyperemia or active hyperemia, whereas the
impaired venous drainage is called venous congestion or passive hyperemia. The ca-
pillaries and veins are dilated and filled with blood.
Arterial or active hyperemia is caused by an increased supply of blood from
arterial system. The affected tissue or organ is pink or red in appearance (erythema).
I. Systemic arterial or active hyperemia is a result of:
increasing volume of circulating blood (plethora).
increasing of erythrocytes amount.
Arterial hyperemia can be physiological and pathological.
II. Local pathological arterial hyperemia can be:
Angioneurotic because of dilatation of arteries and arterioles (owing to
stimulation of vasodilating nerves, or paralysis of vasoconstrictive nerves).
Collateral (due to occlusion of large vessel by thrombus, embolus).
Hyperemia after anemia.
Vacatuos (lat. vacuum) because of decreased atmospheric pressure.
Inflammatory.
In arteriovenous fistula.
Venous, or passive hyperemia, or congestion is caused by impediment to the
exit of blood through venous pathway. The dilatation of veins and capillaries due to
impaired venous drainage results in passive hyperemia or venous congestion com-
monly referred to as congestion. Congestion may be acute or chronic, the latter being
more common and called chronic venous congestion.
I. Systemic (General) venous congestion is engorgement of systemic veins. It
can be a result of:
Left-sided and right-sided heart failure
Diseases of lungs which interfere with pulmonary blood flow, like pulmonary
fibrosis, emphysema, etc.
Cardiac decompensation.
II. Local congestion can be a result of:
Venous obstruction caused by its thrombosis.
Compression of venous vessel by tumor or growth of connective tissue.
Development of collateral blood circulation.
M O R P H OL OGY O F C O N G ES T I ON
Because of the increase in venous blood, organs become swollen and purplish.
With long continued over-distension, the wall of the venules shows reactive thicken-
ing and there is mild intestinal fibrosis of the organs, giving them a very firm con-
sistency. These changes are seen typically in the kidney and spleen. Important addi-
tional changes are found in the lungs and liver.
Lungs. The lungs are heavy, congested and brownish in color. Pulmonary ve-
nous engorgement leads to alveolar multiple diapedetic hemorrhages. Hemoglobin
from intra-alveolar blood is transformed into hemosiderin, which is then phagocyt-
ized by macrophages. These macrophages are known as heart failure cells. Phago-
cytes full of brown pigment migrate into interstitial tissue and to the lymph nodes.
That is why the cut surface is dark brown. Venous congestion causes hypoxia. The
hypoxia stimulates growth of connective tissue. That is why lungs become firm in
consistency. Growth of connective tissue in alveolar septa leads to capillary-
parenchymatous block that reinforces the existing hypoxia. This process in lungs is
named as brown induration of the lungs.
Spleen. Chronic venous congestion of the spleen occurs in right heart failure
and in portal hypertension from cirrhosis of liver. The spleen in early stage is moder-
ately enlarged while in long-standing cases there is a progressive enlargement and it
may weigh up to 500 g to 1000 g. The organ is deeply congested, tensed and cyanotic
(cyanotic induration of the spleen). Sectioned surface is gray tan. The red pulp
shows congestion and marked sinusoidal dilatation with areas of recent and old hem-
orrhages. These hemorrhages may get organized. This advanced stage seen more
commonly in hepatic cirrhosis is called congestive splenomegaly and is the common-
est cause of hypersplenism.
Liver. Chronic venous congestion of the liver occurs in right heart failure and
sometimes due to occlusion of inferior vena cava and hepatic vein. The liver is en-
larged and tender and the capsule is tensed. Cut surface shows characteristic nutmeg
liver due to red and yellow mottled appearance. The changes of congestion are more
marked in the centrolobular zone due to severe hypoxia than in the peripheral zone.
The centrolobular hepatocytes undergo degenerative changes, and eventually centrol-
obular hemorrhagic necrosis may be seen. The peripheral zone of the lobule is less
severely affected by chronic hypoxia and shows some fatty changes in the hepato-
cytes. Growth of connective tissue in sinusoids leads to capillarization of sinusoids
(appearance of continuous capillary like basement membrane that is absent in normal
liver) and capillary-parenchymatous block that reinforces the preexisting hypoxia. If
the patient has periods of remission, the remaining liver cells may undergo compen-
satory hyperplasia. This results in small, irregular, pale nodules alternating with areas
of fibrosis so-called cardiac cirrhosis. It's not true cirrhosis and does not causes he-
patic failure.
Kidney. Grossly, the kidneys are slightly enlarged and the medulla is congest-
ed. Microscopically, the changes are rather mild. The tubules may show degenerative
changes like cloudy swelling and fatty change. The glomeruli may show mesangial
proliferation.
Skin. Cyanosis, dilation of veins and lymph vessels, severe edema of derma
and subcutaneous tissue, sclerosis occur. All the changes described above are the
background for inflammation and ulceration
Serous cavities. Serous coats are cyanotic. Accumulation of fluid leads to cavi-
tary edema (hydrothorax, hydropericardium, anasarca).
Outcomes of congestion:
Edema.
Stasis.
Hemorrhage.
Thrombosis.
Induration of organs.
Atrophy of organs.
HEMORRHAGE
Hemorrhage (i.e. bleeding) is a discharge of blood from the vascular compart-
ment to the exterior of the body or into nonvascular body spaces.
Mechanisms of hemorrhages:
1. By destruction of the blood vessel's wall (e.g. trauma, rupture of aneurysm).
2. By diapedesis of erythrocytes because of the increased permeability of the
vascular wall (e.g. intoxication, hypoxia).
3. By ulceration of the vessel's wall (e.g. ulcer of stomach, necrosis of tumor,
pulmonary tuberculosis). Thus a severe decrease in the number of platelets (thrombo-
cytopenia) or a deficiency of a coagulation factor (e.g., factor VIII in hemophilia) is
associated with spontaneous hemorrhages unrelated to any apparent trauma.
Types of hemorrhages according to the site of origin:
1. Cardiac, as following a penetrating heart wound.
2. Arterial, due to trauma and rupture of a dissecting aneurysm.
3. Capillary, that is usually due to trauma, inherent vessel wall weakness, or a
coagulation defect.
4. Venous, which is usually caused by trauma or surgical operation, from
esophageal varices.
Types of internal hemorrhages
Petechia a small mucosal or serosal hemorrhage or minute punctate hemor-
rhage usually in the skin or conjunctiva.
Purpura or hemorrhagic infiltration the accumulation of some erythro-
cytes in tissue between cells.
Ecchymosis or bruise the superficial large extravasation of blood into the
skin and mucous membranes. Following a bruise in association with coagulation de-
fect, an initially purple discoloration of the skin turns green and then yellow before
resolving, a sequence that reflects the progressive oxidation of bilirubin released from
the hemoglobin of degraded red blood cells. A good example of an ecchymosis is a
black eye.
Hematoma a grossly visible localized accumulation of blood in the soft tis-
sue.
Types of hemorrhages in body cavities:
Hemothorax hemorrhage in the pleural cavity.
Hemopericardium hemorrhage in the pericardium cavity.
Hemoperitoneum hemorrhage in the abdomen cavity.
Hemoarthrosis hemorrhage in the joint cavity.
External hemorrhages may be such as:
Melena is the presence of blood in feces (stool) due to hemorrhage from ulcer
of the stomach, polyp or ulcer of the intestines.
Hemoptysis is hemorrhage from the lungs.
Metrorrhagia is hemorrhage from the uterus.
Outcomes of hemorrhages
Coagulation of the blood.
Organization and encapsulation of the hematoma.
Brown cyst formation (in cerebral hematoma due to accumulation of hemo-
siderin).
Purulent fusion of the hematoma.
In cases of death from acute massive hemorrhage, the most significant post-
mortem changes are gross rather than microscopic. They are the following: general-
ized pallor of tissues, collapse of the great veins, and a flabby, shrunken, gray spleen.
A sudden loss of 33% of blood volume may cause death, while loss of 50% of
blood volume over a period of 24 hours may not be necessarily fatal. However chron-
ic blood loss generally produces an iron deficiency anemia, whereas acute hemor-
rhage may lead to serious immediate consequences such as hypovolemic shock.
ISCHEMIA
Ischemia is the loss of blood supply, which occurs when arterial flow is imped-
ed by atherosclerosis or by thrombi, or by some other causes. Ischemia is the most
common cause of hypoxia.
Types of ischemia
Angiospastic (reflex).
Obstructive.
Compressive.
Ischemia because of redistribution of blood.
Morphologic features
The primary response of acute ischemia is cellular swelling or edema with di-
lation of the endoplasmic reticulum, dissociation of polysomes into monosomes,
swelling of mitochondria, and also increased concentration of water, sodium, and
chloride and decreased concentration of potassium into the cytoplasm. If the duration
of ischemia is short, the structure and the function of tissue may be restored.
If ischemia persists, irreversible injury ensures with severe vacuolization of
the mitochondria including their cristae, extensive damage to cytoplasmic membrane,
and swelling of lysosomes. When the lesion is continuous, infarction, atrophy or scle-
rosis may develop.
STASIS
Stasis (stasis stop) is the arrest of blood flow in the vessels of microcirculato-
ry system (capillaries). The capillaries and veins are dilated simultaneously and filled
with blood. In the lumen of some capillaries homogenous eosinophilic masses can be
seen. They are columns of erythrocytes stuck together, which is called prestasis.
Sludge syndrome (phenomenon) is regarded as a type of stasis. It is characterized by
sticking of erythrocytes, leukocytes and thrombocytes to each other, which is accom-
panied by blood viscosity increase.
Stasis may be discirculatory as a result of venous hyperemia or ischemia.
Causes of stasis:
Physical factors (temperature elevation, cold).
Chemical factors.
Infection.
Infectious-allergic factors.
Autoimmune factors.
Short stasis is reversible, long one causes hyaline thrombi formation, vascular
permeability increase, edema, bleeding.
Isolated vein spasm may cause leukostasis, accumulation of erythrocytes with-
in venules (small veins) and capillaries. It is observed in hypoxia. In shock, leukosta-
sis may be generalized, but as a rule it is localized in venules.
Microcirculation disturbances.
There are four links in microcirculation:
l. The link of inflow and distribution of the blood (arterioles and precapillar-
ies).
2. Intermediate (exchange) link (capillaries).
3. Depot link (postcapillaries and venules).
4. Drainage link (lymphatic capillaries and postcapillaries). The function of
microcirculation is exchange between the blood and tissue. Pathology of microcircu-
latory system is formed by vascular, intravascular and extravascular changes.
Vascular changes are those in the thickness and shape changes of the vessels,
angiopathies with disturbance of vascular permeability as a result of hypoxia.
Intravascular changes manifest as different disturbances of blood rheology
(sludge, prestasis, stasis). They are observed in shock of different origin.
Intravascular changes are perivascular edema, hemorrhage, lymphostasis in the
lymph vessels.
Plasmorrhagia means outflow of plasma from vessels. The cause of plas-
morrhagia is increased vascular permeability. The consequence of plasmorrhagia is
plasmatic impregnation.
Mechanism of development. The development of plasmorrhagia is defined by
two conditions: damage of microvascular bed (caused by tissue hypoxia, neurovascu-
lar disturbances (spasm), immunopathologic reactions and blood constant changes
(disorders of rheological properties, increased content of lipoproteins, immune com-
plexes, vasoactive substances, and natural anticoagulants in blood). Increased perme-
ability of vessels leads to accumulation of plasma proteins in vessels walls with the
denaturation, precipitation, and coagulation of them. Accumulation and transfor-
mation of blood plasma proteins lead to the injury of vascular basement membrane,
elastic membranes, and endothelial cells.
Microscopic characteristic. Vascular walls are thickened, homogeneous. In se-
vere cases fibrinoid necrosis occurs.
Outcome: hyalinosis.
Lymph circulation disturbance
Lymph circulation disturbance manifests itself as lymphatic system insuffi-
ciency. There are mechanical, dynamic and resorption insufficiencies of lymphatic
system.
Mechanical insufficiency is caused by factors that block lymph flow. These
factors are: lymphatic vessel compression and occlusion, blockage of lymph nodes by
cancer cells, extirpation of thoracic duct, lymphatic vessel valves insufficiency. Dy-
namic insufficiency is caused by increased filtration in capillaries. In the case of in-
creased capillary filtration lymph vessels are incapable of removing edematic fluid
from interstitial tissue. Resorption insufficiency occurs in tissue proteins biochemical
and dispersion properties alteration or when lymph vessels permeability decreases.
Combined insufficiency predominates over other forms.
Morphological changes.
Lymph congestion and lymphatic vessels dilation, development of collateral
lymph flow with lymphatic capillaries and lymphatic vessels changes; development
of lymphectasia; development of lymphedema, lymph stasis and protein thrombi for-
mation; lymphorrhea; development of chylous (milky) ascites and chylothorax. All
morphological changes listed above are the stages of lymphatic system insufficiency.
Lymphedema can be acute and chronic. Each of them can be general and local.
Acute general lymphedema is rare and caused by bilateral thrombosis of sub-
clavian veins.
Chronic general lymphedema occurs in chronic venous congestion i.e. in
chronic heart failure (IHD, heart valvular disease, cor pulmonale).
Acute local lymphedema occurs in occlusion of lymphatic vessels (by cancer
metastases), lymphatic vessels compression (at surgical procedures), in acute lym-
phadenitis etc.
Chronic local lymphedema can be congenital (in lymphatic vessels hypoplasia
and aplasia) and acquired (in lymphatic vessels compression by tumor, chronic in-
flammation with sclerosis, thrombosis of veins etc). Chronic lymph congestion leads
to hypoxia. Hypoxia causes sclerotic changes in tissues. Skin and subcutaneous adi-
pose tissue of extremities become dense, increased in volume. These changes are
called elephantiasis.
Outcomes.
Acute lymphedema: dystrophic and necrobiotic changes. Chronic lymphedema:
atrophic and sclerotic changes, lymphogenous induration of organs.
3. Class work.
1 Nutmeg liver. Liver is enlarged in size, firm, the surface of the liver is
smooth. The cut surface shows red-brown foci on the yellow background and resem-
bles nutmeg. Explain the reason for such changes.
270, 270-, 271-, 272 Haemorrhage into the brain. There is accumula-
tion of coagulated blood in different areas of brain. There is a damage of brain matter
in the areas of hemorrhages (hematomas). Name the most likely mechanisms of oc-
currence of such haemorrhage and possible outcomes of it.
34 Bleeding stomach ulcer. Find the damaged blood vessel in the bottom
of the ulcer. Name the most likely mechanisms of development. Outcomes.
29 Haemorrhagic gastritis. Find black foci of hemorrhages in the mu-
cous membrane of the stomach. Name the most likely mechanisms of development.
44 Cyanotic induration of spleen. (st. hematoxylin and eosin). Pay atten-

tion to the severe hyperaemia of the parenchyma and sclerosis of collagen fibers in
the stroma.
42 Nutmeg liver. (st. hematoxylin and eosin). Describe the changes in the
hepatocytes in different zones of the hepatic lobulus.
Hyperemia of cen-
tral veins
43 Brown lung indurations (hematoxylin and eosin st. A, Prussian blue
reaction (Perls st.) B). Pay attention to the status of vessels in interalveolar septum
(II barrier). Find grains of the brown pigment on Figure A and blue pigment on Fig-
ure B. Note its localization and arrangement in lung tissue. Characterize the status of
alveolar cavities. What is the name of cells that contain hemoglobin pigment and are
localized in the lumen of alveolus and small bronchia?
A B
98 The haemorrhage into the pia mater encephali. (st. hematoxylin and
eosin). Pia mater encephali is thickened, infiltrated by blood. There are stases in small
arteries and capillaries as well as perivascular and pericellular edema. Define the most
likely mechanism of this haemorrhage development. Draw.
Hemorrhage
41 Stasis in vessels of the brain. (st. hematoxylin and eosin). Note the
condition of small and larger vessels, the status of capillaries and erythrocytes in
them.
Stasis
Perivascular
edema
III. Complete the table (see theoretical part).
Kinds of blood supply disturbances

Kind Causes Mechanisms of development Outcomes
Plasmorrhagia Increased Accumulation of blood plasma proteins in vascular Hyalinosis
vascular walls with the denaturation, precipitation, and
permeability coagulation of them. Injury of vascular basement
membrane, elastic membranes, and endothelial cells
Chronic general venous (chronic cardiovascular insufficiency) congestion

Etiology Changes in organs
Lungs Liver Kidney Spleen Serous cavities Skin
4. Clinical tasks.
1. A patient underwent surgical removal of liver Echinococcus that was situated un-
der the liver capsule. The patient died of anemia. At autopsy, blood was found in the
abdominal cavity.
1. What is the kind of bleeding?
2. What type of hyperemia promoted the bleeding?
2. A patient who suffered from stomach ulcer died of gastric bleeding. At autopsy,
severe anemia of organs and tissues was revealed.
1. What is the type of anemia?
2. What is the gross appearance of organs (colour, consistence, size)?
3. A patient suffering from congenital aneurism of the medial cerebral artery sud-
denly died. At autopsy, blood accumulation and destruction of brain tissue in the left
temporal lobe were revealed.
1. What is the mechanism of hemorrhage?
2. What is the type of the hemorrhage?
4. On postmortem examination of a patient with atherosclerosis, almost total occlu-

sion of coronary arteries with atherosclerotic plaques was revealed. He had no symp-
toms of cardiac failure during his lifetime.
1. Why were the symptoms of cardiac failure absent?
2. What is the cause of that?
5. At autopsy, a patient with heart valvular disease has edema and varicose dilation
of veins in lower limbs, ascites, and hydrothorax.
1. What is the reason for these pathological changes?
2. What changes can be found in other organs of the patient?
ANSWERS
1 2
1 Parenchymatous Hyperemia after anemia promoted the bleeding
2 Posthemorrhagic Pallor, flabby, decreased in size
3 Rapture of aneurism Hematoma
4 Because of collateral blood 1. Slow and gradual occlusion of vascular lumen in long
supply term atherosclerosis;
2. Particularities of organ blood supply.
5 Chronic systemic venous con- Nutmeg liver, brown lung induration, cyanotic induration
gestion of spleen and kidneys
5. Self assessment.
1. Active hyperaemia is the result of:
1. Dilatation of capillaries
2. Dilatation of arterioles
3. Venous engorgement
4. Lymphatic obstruction
5. Dilatation of lymphatics
2. Microscopically, acute pulmonary congestion is characterized by all of the following,
EXCEPT:
1. Engorged alveolar capillaries
2. Thickened and fibrotic alveolar septa
3. Edema fluid in alveoli
4. Focal intra-alveolar hemorrhage
5. Foci of atelectasis
3. Microscopically, acute hepatic congestion is characterized by all of the following,
EXCEPT:
1. Engorged central veins
2. Engorged central sinusoids
3. Destroyed central hepatocytes
4. Unchanged periportal sinusoids
5. Diminished periportal hepatocytes
4. Microscopically, chronic pulmonary congestion is characterized by all of the following,
EXCEPT:
1. Engorged alveolar capillaries
2. Thickened and fibrotic alveolar septa
3. Focal intra-alveolar hemorrhage
4. Numerous heart failure cells in lung tissue
5. Abscesses in lung tissue
5. Macroscopically, chronic passive congestion of the liver is characterized by all of the
following, EXCEPT:
1. Hemorrhagic and wet cut surface
2. Red-brown central areas of the hepatic lobules
3. Goose liver
4. Tan periportal areas (fatty changes)
5. Nutmeg liver
6. Microscopically, chronic passive congestion of the liver is characterized by all of the fol-
lowing, EXCEPT:
1. Centrolobular necrosis of hepatocytes
2. Centrolobular hemorrhages
3. Engorged periportal sinusoids
4. Capillarization of sinusoids
5. Fatty changes of periportal hepatocytes
7. Reduced plasma osmotic pressure results from all of the following, EXCEPT:
1. Nephrotic syndrome
2. Liver cirrhosis (ascites)
3. Protein malnutrition
4. Protein-losing gastroenteropathy
5. Thrombosis
8. Conditions that result in edema because of increased hydrostatic pressure are all of the
following, EXCEPT:
1. Congestive heart failure
2. Inflammation
3. Ischemic heart disease
4. Systemic hypertension
5. Venous obstruction or compression
9. Pathophysiologic mechanisms of edema are all of the following, EXCEPT:
1. Inflammation
2. Sodium retention
3. Calcium retention
4. Hypoproteinemia
5. Increased hydrostatic pressure
10. A severe and generalized edema with profound subcutaneous tissue swelling is called:
1. Anasarca
2. Ascites
3. Hydrothorax
4. Hydropericardium
5. Hydrocele
11. Generalized edema as a result of renal dysfunction or nephrotic syndrome is localized
in:
1. Periorbital tissue
2. All parts of the body
3. Lung
4. Brain
5. Liver
12. Pulmonary edema commonly results from all of the following, EXCEPT:
1. Left ventricular failure
2. Renal failure
4. Appendicitis
5. Myocardial infarction
13. Ascites develops if venous outflow is impaired from this organ:
1. Lung
2. Brain
3. Liver
4. Lower extremities
5. Upper extremities
14. Minute (1- to 2-mm) hemorrhages into skin, mucous membranes or serosal surfaces
are called:
1. Hematomas
2. Petechiae
3. Purpura
4. Ecchymoses
5. Hemothorax
15. The most common underlying cause of primary brain parenchymal hemorrhage is
which of the following:
1. Systemic coagulation disorders
2. Vasculitis
4. Neoplasms
5. Vascular malformations
16. Small (0.3 to 1.0 cm) hemorrhages into skin, mucous membranes or serosal surfaces
are called:
1. Hematomas
2. Petechiae
3. Purpura
4. Ecchymoses
5. Hemothorax
17. Macroscopically, brain hemorrhage is characterized by all of the following, EXCEPT:
1. Local extravasation of blood
2. Local damage of brain tissue
3. Narrowed cerebral sulci
4. Distended cerebral gyri
5. Cavitary destruction of brain
18. Large (>1 to 2 cm) subcutaneous hemorrhages are called:
1. Hematomas
2. Petechiae
3. Purpura
4. Ecchymoses
5.Hemothorax
19. Large accumulations of blood in one or another of the body cavities are termed as all
of the following, EXCEPT:
1. Hemothorax
2. Hemopericardium
3. Hemosiderosis
4. Hemoperitoneum
5. Hemarthrosis
20. Microscopically, brain hemorrhage is characterized by all of the following, EXCEPT:
1. Fatty changes of damaged neurons
2. Central core of clotted blood
3. Edema of adjacent brain tissue
4. Dystrophy of survived neurons
5. Reactive proliferation of astrocytes
ANSWERS
1 2 11 2
2 2 12 4
3 5 13 3
4 5 14 2
5 3 15 3
6 3 16 3
7 5 17 5
8 2 18 4
9 3 19 3
10 1 20 1
Class 6
Theme: Haemodynamic disturbances. Thrombosis, embolism, infarction,
shock, DIC syndrome

1. Thrombosis: the definition, mechanism of blood clot formation. Kinds and
morphology of blood clot. Fate and effect on organism.
2. Embolism: the definition, kinds and mechanisms of emboli occurrence. Fate
and effect of embolism on organism.
3. Infarction: definition, kinds, pathogenesis, fate.
4. Haemorrhagic infarction: the mechanism of its occurrence and outcomes.
5. DIVC syndrome: the causes, the mechanism of development, morphological
changes in organs.
6. Shock: the causes, morphology, effect on organism, fate.
THROMBOSIS
Thrombosis is a pathologic process, characterized by intravital coagulation of
blood in the lumen of vessels or heart in the unruptured cardiovascular system.
Primary events predisposing to thrombosis (Virchows triad):
1. Endothelial injury;
2. Alterations of blood flow;
3. Hypercoagulability of blood.
Types of thrombi
According to the degree of the lumen obstruction, thrombi may be:
Occlusive thrombi most commonly develop in small arteries and veins.
Wall-attached or mural thrombi develop in large arteries and heart cavities.
Globe-shaped (in the heart).
According to the morphology
Thrombi may be of various shapes, size and composition depending upon the
site of origin. Thrombus is attached to the vascular wall; it is dense, with corrugated
surface. It is composed of branching bars of stuck thrombocytes and bands of fibrin
with erythrocytes and leukocytes located between them.
MORPHOLOGICAL TYPES OF THROMBI
White thrombus consists mainly of platelets, fibrin and leukocytes; forms
slowly in rapid circulation of blood (usually in the arteries);
Red thrombus consists of platelets, fibrin and excessive amount of eryth-
rocytes; forms rapidly in slow blood circulation (usually in veins). Venous thrombi
are dark-red colored dry masses with dim surface.
Mixed or laminated thrombus has laminated structure, contains white and
red elements of thrombus (usually forms in veins, aneurysms of aorta and heart).
Mixed thrombus consists of core or head (white thrombus), body (white and red) and
tail (has construction of red thrombus). Core is connected with endothelium. Mixed
thrombus is of gray-red color with rough dim surface, fixed to the intima of the ves-
sel. Body and tail are located freely in the vessel's lumen.
Hyaline thrombus consists of precipitating plasma proteins, destroyed eryth-
rocytes, leukocytes and thrombocytes. They contain fibrin. They resemble hyaline
and are located in the microcirculatory bed.
The distinguishing features between thrombi formed in rapidly-flowing arterial
circulation and low-moving venous blood are given in Table 3.
FATE OF THROMBOSIS
Favourable outcomes:
Aseptic autolysis (dissolution) by fibrinolytic system, proteinolytic enzymes
of macrophages and leukocytes.
Organization by the replacement of connective tissue.
Recanalization is the re-establishment of the vascular lumen through occlud-
ing thrombus.
Vascularization means restoration of the circulation in the vessel because of
the formation of the new vessels through the thrombotic mass.
Petrification or dystrophic calcification accumulation of the calcium salts in
the thrombotic masses.
Unfavourable outcomes:
Thromboembolism.
Septic autolysis.
Propagation with following obstruction of some critical vessel.
TABLE 1 DISTINGUISHING FEATURES OF ARTERIAL AND VENOUS

THROMBI
FEATURE ARTERIAL THROMBI VENOUS THROMBI
l. Blood flow Formed in rapidly-flowing blood of arter- Formed in slow-moving blood in veins
ies and heart
2. Sites Common in coronary, cerebral, iliac and Common in superficial varicose veins,
femoral arteries deep leg veins, popliteal, femoral and
iliac veins
3. Thrombo- Formed following endothelial cell injury, Formed following venous stasis, e.g. in
genesis e.g. in atherosclerosis abdominal operations, childbirth
4. Develop- Usually mural, not occluding the lumen Usually occlusive, take the cast of the
ment completely, may propagate. vessel in which formed, may propagate in
both directions.
5. Macrosco- Grey-white, friable with lines of Zahn on Red-blue with fibrin strands and lines of
py surface Zahn
6. Microsco- Distinct lines of Zahn composed of plate- Lines of Zahn with more abundant red
py lets, fibrin with entangled red and white cells
blood cells
7. Effects Ischemia leading to infarcts, e.g. of heart, Thromboembolism, edema, skin ulcers,
brain etc. poor wound healing
Red thrombi (ante-mortem) have to be distinguished from postmortem clots
(Table 2).
TABLE 2 ANTEMORTEM THROMBI VERSUS POSTMORTEM CLOTS

ANTEMORTEM THROMBI POSTMORTEM CLOTS
1. Dry, granular, firm and friable Gelatinous, soft and rubbery
2. Adherent to the vessel wall Weakly attached to the vessel wall
3. May or may not fit their vascular con- Take the shape of vessel or its bifurcation
tours
4, The surface contains apparent lines of The surface is "chicken fat" yellow covering the
Zahn. underlying red "currant jelly".
EMBOLISM
Embolism is the circulation of any mass in blood or lymph obstructing the lu-
men which is absent in normal conditions. The transported intravascular mass de-
tached from its site of origin is called an embolus.
Types of embolism
According to localization:
Lesser (pulmonary) circulation.
Greater (systemic) circulation.
Portal vein system.
According to the direction of emboli circulation:
Orthograde (by blood flow)
Retrograde (against blood flow).
Paradoxical (emboli arising in the venous circulation may bypass the lungs by
migrating through an incompletely closed foramen ovale, subsequently blocking flow
in systemic arteries).
According to the matter of the embolus:
1. Solid:
Thromboembolism.
Atheroembolism.
Tissue (cellular) embolism due to necrosis of tumor, damaged tissue.
Bacterial embolism.
Embolism by parasites.
Embolism by foreign bodies.
2. Liquid:
Fat embolism.
Amniotic fluid embolism.
3. Gaseous:
Decompression sickness (caisson disease).
Air embolism.
Thromboembolism.
A detached thrombus or part of thrombus constitutes is the most common type
of embolism. These may arise in the arterial or venous circulation:
The effects of arterial emboli depend upon their size, site of lodgement, and
adequacy of collateral circulation:
Infarction.
Gangrene.
Arteritis and mycotic aneurysm.
Myocardial infarction.
Sudden death.
The most significant effect of venous embolism is the obstruction of pulmo-
nary arterial circulation leading to pulmonary embolism.
Atheroembolism. Atheromatous plaques, especially from aorta, may get eroded
to form atherosclerotic emboli. The pathologic changes and their effects are:
Ischemia, atrophy and necrosis,
Infarcts in the affected organs,
Gangrene in the lower limbs,
Hypertension.
Fat embolism. Obstruction of arterioles and capillaries by fat globules consti-
tutes fat embolism. If the obstruction in the circulation is by fragments of adipose tis-
sue, it is called fat-tissue embolism. Important causes are: trauma, inflammation of
bones and soft tissues, fatty liver, pancreatitis, extrinsic fat or oils introduced into the
body.
Gas Embolism. Two main forms of gas embolism are air embolism and de-
compression sickness.
Air Embolism occurs when air is introduced into venous or arterial circulation.
Causes of venous embolism include: operations on the head and the neck, and
trauma, obstetrical operations, intravenous infusion of blood and fluid, angiography.
The effects of venous air embolism depend upon the following factors: amount of air
usually 100-150 ml of air entry is considered fatal, rapidity, position of the patient
during or soon after entry of air. The air bubbles may ascend into the superior vena
cava if the position of head is higher than the trunk (e.g. in upright position) and
reach the brain. General condition of the patient e.g. in severely ill patients, as little as
40 ml of air may have serious results.
Causes of arterial embolism include: cardiothoracic surgery and trauma, par-
adoxical air embolism, arteriography. The effects of arterial air embolism are certain
characteristic features: marble skin due to blockage of cutaneous vessels, air bubbles
in the retinal vessels seen ophthalmoscopically, pallor of the tongue due to occlusion
of a branch of lingual artery, coronary or cerebral arterial air embolism may cause
sudden death by much smaller amounts of air than in the venous air embolism.
Gas embolism. The specialized form of gas embolism is known by various
names such as caisson's disease, divers' palsy or decompression sickness. Decom-
pression sickness is produced when the individual decompresses suddenly, either
from high atmospheric pressure to normal level or from normal pressure to low at-
mospheric pressure.
Tissue (cellular) embolism. Amniotic Fluid Embolism. This is the most seri-
ous, unpredictable and unpreventable cause of maternal mortality. During labour and
in the immediate post-partum period, the contents of amniotic fluid may enter the
uterine veins and reach right side of the heart resulting in fatal complications. Notable
changes are seen in the lungs such as hemorrhages, congestion, edema, and dilatation
of right side of the heart. These changes are associated with identifiable amniotic flu-
id contents within the pulmonary microcirculation.
The cause of death may be a result of the following mechanisms:
Mechanical blockage of the pulmonary circulation,
Anaphylactoid reaction to amniotic fluid,
Disseminated intravascular coagulation (DIC),
Hemorrhagic manifestations due to thrombocytopenia and afibrinogenemia.
Tumor embolism. Malignant tumor cells invade the local blood vessels and
may form tumor emboli to be lodged elsewhere, producing metastatic tumor deposits.
Notable examples are clear cell carcinoma of kidney, carcinoma of the lung, malig-
nant melanoma etc.
Bacterial embolism. It occurs in purulent lysis of thrombi (e.g. sepsis). They
may be lodged in lungs, kidneys, spleen, heart etc. There is a development of abscess
in the place of their location.
SHOCK
Shock is acute pathologic process due to development of extrapowerful stimuli
and characterized by disturbances in CNS function, metabolism and microcirculatory
system autoregulation resulting in destructive changes in the organs and tissues.
According to etiology and pathogenesis shock is classified as:
1. Hypovolemic (blood loss, trauma, peritonitis, cholera).
2. Cardiogenic (caused by the reduction in cardiac output in myocardial infarc-
tion, vascular insufficiency).
3. Bacterial (caused by endotoxins).
4. Anaphylactic (immediate reaction of hypersensitivity).
5. Neurogenic (in intoxication with hypnotic preparations, ganglioblockers,
narcotics).
6. Shock developing as a result of obstruction of blood flow (pulmonary
thromboembolism).
7. Shock developing in hormonal insufficiency (thyrotoxic shock, myxedema,
adrenal insufficiency).
Shock morphology
Three main pathological processes are observed in shock: DIC (disseminated
intravascular coagulation) syndrome, hemorrhagic diathesis, liquid cadaver blood.
Microscopically it is characterized by generalized spasms of the vessels, micro-
thrombosis, signs of increased vascular permeability in microcirculatory system,
hemorrhages, degenerations, necroses connected with hypoxia and damaging effect
of endotoxins.
Some examples of changes in the different organs in shock are:
shock kidney, degeneration and necrosis in proximal canals with development
of necrotic nephrosis (or symmetrical cortical necroses are possible) which results in
acute renal insufficiency,
shock liver, glycogen amount in the hepatocytes decreases, hydropic degen-
eration and centrolobular necroses resulting in acute hepatic insufficiency develop.
Combination of renal and hepatic insufficiency is called hepatorenal syndrome,
shock lung, atelectasis foci, serous-hemorrhagic edema, stases and thrombo-
ses in the microcirculatory bed resulting in acute respiratory insufficiency,
shock heart, degeneration and necrosis in cardiomyocytes, reduction in gly-
cogen amount, fat degeneration, foci of necrosis,
shock gastrointestinal, the hypoperfusion of alimentary tract may result in
mucosal and mural infarction called hemorrhagic gastroenteropathy,
shock brain, hypoxic changes in the brain. Ischemic neurons appear shrunken
and have eosinophilic cytoplasm. The pericellular spaces are dilated because of ede-
ma. Dead and dying nerve cells are replaced by gliosis.
Similar changes occur in endocrine systems and immune organs.
Shock morphology depends not only on the cause of the shock but also on its
stage. At the early stage, disturbances of hemodynamics and DIC (disseminated in-
travascular coagulation) syndrome are noted. At the last stages degenerative and ne-
crotic processes occur.
Intensive transfusion therapy of shock masks clinicomorphological picture. But
the constant features are liquid cadaver blood irrespective of the composition of
transfused fluids. Blood clots in the cardiac cavities and vessels are characteristic for
terminal states of nonshock origin. So blood composition is a criterion for differential
diagnosis.
Disseminated intravascular coagulation (consumption coagulopathy, defib-
rination, thrombohemorrhagic syndrome or phenomenon) is a pathological syndrome
which is characterized by formation of disseminated blood clots in the micro-
circulatory bed (often in combination with simultaneous reduction of blood coagula-
bility) causing hemorrhages. It often develops in complicated pregnancy, profuse
uterine bleedings, Cesarean section, large injuries, anemias, thrombocytopenias, leu-
kosis, in 36-50% of cases of asphyxia in premature children.
The causes of its development are numerous, the mechanisms of development
are different.
The most important are:
1. Massive formation of thromboplastin or its activators. It may be thrombo-
plastin of erythrocytes in intravascular hemolysis (hemolytic disease of newborn,
massive blood transfusions, poisoning, infections) or thromboplastin of amniotic fluid
on massive aspiration of amniotic fluid by the fetus, tissue thromboplastin in injury
(especially that of brain and lungs).
2. Generalized disturbance of microcirculation accompanied by changes in
blood rheology and its clotting which is observed in hypoxia and shock of different
origin. Bacterial toxins and immune complexes act similarly. They activate factor XII
which plays the most important role both in blood coagulation and anticoagulation
activation. The same mechanism regulates disseminated intravascular coagulation
syndrome in thrombosis of large arteries or in severe loss of fibrinogen in the for-
mation of hyaline membranes in the lungs of newborns.
3. Reduction of the number of thrombocytes (consumption thrombocytopenia
in Kasabach-Merritt syndrome).
4. Generalized angiopathy in infectious diseases and hemolytic disease of new-
born also causes disseminated intravascular coagulation syndrome. At the first stage
it is characterized by generalized increase of blood coagulation in the microvessels.
Large numbers of fibrin clots are formed. They close the vessel (fibrinoembolism).
At the second stage the amount of thrombocytes, fibrinogen, protrombin in the
blood decreases sharply because they have already been used at the first stage with
the resultant consumption coagulopathy. Thus, hemorrhagic syndrome develops.
At the third stage fibrinolysis activation takes place in response to generalized
increase of coagulation occurring at the first stage which makes hemorrhagic syn-
drome more severe.
In severe cases the three stages develop simultaneously. Disturbance in blood
clotting is accompanied by stasis, opening of arteriovenous shunts, capillary paraly-
sis, decrease in arterial pressure. Degenerative and necrotic changes develop in paren-
chymatous organs.
Morphological changes in disseminated intravascular coagulation (DIC) syn-
drome:
1) large amount of fibrin thrombi and emboli in the small vessels of the liver,
red pulp of spleen, adrenals, brain, lungs, kidneys, placenta, thymus,
2) mucoid swelling, fibrinous swelling and fibrinous necrosis with endothelium
desquamation in the walls of small arteries,
3) thrombosis of large vessels are possible. Often the thrombi occur in the si-
nuses of the dura mater, hepatic veins, aorta,
4) in thrombosis of microcirculatory bed, vital processes of blood-tissue me-
tabolism stop. Under these conditions organ pathology is not distinct, general changes
(like toxicosis or shock) develop,
5) in thrombosis of larger arteries, organ pathology prevails, i.e. acute renal or
hepatic insufficiency, shock lung, brain edema, myocardial infarction,
6) DIC (disseminated intravascular coagulation) results in hemorrhages in dif-
ferent organs, those in the capsule are most frequent.
INFARCTION
Infarction is an area of ischemic necrosis within tissue or an organ, produced
by occlusion of either its arterial supply or its venous drainage.
Types of infarctions:
Ischemic (white) infarction is encountered in arterial occlusion and in solid
tissues (spleen).
Red (hemorrhagic) infarction is encountered in venous occlusion, in tissues
with double circulation, and in tissues previously congested (lung, intestine).
White infarction with hemorrhagic crown (kidneys, heart).
According to their age, infarcts are classified as:
Recent or fresh.
Old or healed.
According to the propagation it may be
Total (when the whole organ is affected).
Subtotal (when only a part of the organ is affected).
Microinfarct (when observed only microscopically).
Pathogenesis
The process of infarction takes place as follows:
Localised hyperemia due to local anoxemia.
Within a few hours, the affected part becomes swollen due to edema and
hemorrhage.
Cellular changes such as cloudy swelling and degeneration appear early.
There is a progressive autolysis of the necrotic tissue and hemolysis of the red
cells.
An acute inflammatory reaction and hyperemia appear at the same time in the
surrounding tissues.
Blood pigments, hematoidin and hemosiderin, liberated by hemolysis are de-
posited in the infarct.
Following this, there is a progressive ingrowth of granulation tissue from the
margin of the infarct.
MORPHOLOGIC MANIFESTATIONS
Myocardial infarction usually develops due to thrombosis of coronary artery.
This infarction shows coagulative necrosis of myocardial cells. Almost no blood is
seen in the vessels. The nuclei of muscles fibers and stroma cells are absent. The pe-
ripheral portion of the infarction has been invaded by acute inflammatory cells, which
act as scavengers and remove the dead cells.
It is the white infarction with hemorrhagic crown. It is classically irregular in
shape with hemorrhagic infiltration on the periphery.
Infarction of the lungs. Embolism of the pulmonary arteries may produce
pulmonary infarction, though not always. The pulmonary infarcts are classically
wedge-shaped with base on the pleura, hemorrhagic, variable in size, and most often
in the lower lobes. Fibrinous pleuritis usually covers the area of infarct. Cut surface is
dark purple and may show the blocked vessel near the apex of the infarcted area. Old
organized and healed pulmonary infarcts appear as retracted fibrous scars. The char-
acteristic feature is coagulative hemorrhagic necrosis of the alveolar walls.
Renal infarction is common, found in up to 5% of autopsies. Renal infarcts
are often multiple and may be bilateral. Characteristically, they are pale or anemic
and wedge-shaped with base resting under the capsule and apex pointing towards the
medulla. Generally, a narrow rim of preserved renal tissue under the capsule is spared
because it draws its blood supply from the capsular vessels. The affected area shows
characteristic coagulative necrosis of renal parenchyma i.e. there are shadows of renal
tubules and glomeruli without intact nuclei and cytoplasmic content.
Infarction of the spleen is one of the common sites for infarction. Splenic in-
farction results from occlusion of the splenic artery or its branches. Splenic infarcts
are often multiple. They are characteristically pale or anemic and wedge-shaped with
their base at the periphery and apex pointing towards hilum. Coagulative necrosis and
inflammatory reaction are seen.
Occlusion of an artery or vein may have little or no effect on the involved tis-
sue or it may cause death of the tissue and, indeed, of the individual. The major de-
terminates include:
The nature of the vascular supply.
The rate of development of the occlusion.
The vulnerability of the tissue to hypoxia.
Clinical significance of infarction
Most of the cardiovascular deaths result from myocardial and cerebral infarc-
tion. Pulmonary infarction is an extremely common complication in a variety of clin-
ical settings. Ischemic necrosis (gangrene) of the lower extremities is a relatively un-
usual clinical problem in the population at large but is a major concern in diabetes
mellitus.
3. Class work.

147 Aortic thrombosis. Pay attention to the kind of blood clot, its locali-
zation in the aorta. What complications can develop?
148- Aneurysm of the aorta with the thrombosis. Note the most prob-
able causes of development.
151- Myocardial infarct. Extensive transmural infarct of left ventricle
with thrombosis of endocardium.
151 Rupture of left ventricular wall. Explain the causes of left ventricu-
lar wall rupture.
246- Infarct of spleen. Find pale infarct with hemorrhagic crown.
191 Haemorrhagic infarct of the lung. Pay attention to the infarct shape,
its arrangement, color.
109- Myocardial infarction. (hematoxylin and eosin staining). De-
scribe the boundaries of infarct (demarcation zone). Find area of necrosis, living my-
ocardial fibers.
Necrotic zone
Demarcation
zone
Living zone
39 Haemorrhagic infarct of the lung. (hematoxylin and eosin staining).

Study and draw. Determine the zone of infarct and normal tissue and determine char-
acter of changes in lung tissue in the zone of infarct.
Hemorrhagic
infarct
40 Ischemic infarct of kidney (hematoxylin and eosin staining). Using
small magnification find necrotic zone and perifocal inflammation with full blood ves-
sels and inflammatory infiltration. Study. Draw.
Ischemic infarct
47 Fat embolism of the lung (staining by Sudan 3). Study and pay atten-
tion to the contents of capillaries.
Fat emboli
III. Fill in the tables:
Blood clots classification

Kind of Relation to The mechanism of Gross appearance Microscopic structure
clot the vessel wall development
Red Occlusive Rapid formation Soft, red and gelat- Platelets, fibrin, nu-
thrombus when blood flow is inous merous red blood cells
slow
Embolism
Embolism kind Causes Outcomes
Thromboembolism Mural thrombi, warty endocarditis, prosthetic heart valve, Infarction, gan-
cardiomyopathy, atherosclerosis, aortic aneurysm, deep grene
vein thrombosis
Infarct
Shape of infarction Morphological kind Organs affected Outcomes
Wedge-shaped Red Lung, kidney (in Organization, suppura-
chronic venous con- tion,
gestion)
4. Clinical tasks.
1. At autopsy, the following changes in intima of aorta were found: multiple yel-
lowish-whitish plaques with focal ulceration; in abdominal part of aorta crumbling
grey-red masses adherent to the vessel wall with dim, rugged surface, narrowing vas-
cular lumen. In pulmonary artery red, gelatinous and rubbery masses with smooth
surface weakly attached to vascular wall were revealed.
1. Which one of the found clots was a thrombus? Which one was postmortem
clot?
2. What changes of vessel promoted thrombus formation?
2. A man who suffered from chronic ischemic heart disease had surgical prosthetics
of coronary artery. Microscopic examination of the removed artery revealed severe
sclerosis in intima. The stenosed lumen of the artery had a firm mass composed of
red blood cells, fibrin and leucocytes, with large foci replaced by connective tissue
that had clefts covered by endothelium.
1. What is the name of the mass found in the artery?
2. What changes happened in this mass?
3. What changes occurred in the heart as complications of this mass formation in
the coronary artery?
3. A man who suffered from heart valvular disease had symptoms of chronic heart
failure, and severe edema of lower limbs. The patient when trying to get out of bed
suddenly developed cyanosis of the face and died.
1. What complication occurred?
2. What changes can be found in lower limbs (relevant to mortal complication)?
3. What is the thanatogenesis?
4. A man who developed myocardial infarction had chronic aneurism of the heart
with thrombosis of its cavity. He reported about sudden pain in the right lumbar area,
blood was identified in urine. Ultrasonic examination revealed change of echogenici-
ty in right kidney.
1. What pathological process occurred in kidney?
2. What is the macroscopic characteristic of this process?
3. What is the cause of this process?
5. A patient who suffered from lower limbs thrombophlebitis for a long period of
time died of acute renal failure. At autopsy, a patent foramen ovale was found.
1. What is the cause of kidney damage?
2. What is the mechanism of this complication development?
ANSWERS
1 1 2 3
In aorta thrombus, in Plaques with ulceration in intima of aorta
pulmonary artery
postmortem clot
2 Thrombus Organization, canalization and vascularization Infarction,
large focal
cardiosclerosis
3 Thromboembolism of Deep veins thrombosis Pulmocoronary
pulmonary artery reflex led to
cardiac arrest
4 Infarction Pale infarction with hemorrhagic crown Thromboem-
bolism
5 Kidney infarction as the Migration of embolus from the veins to the
result of renal artery arteries through the patent foramen ovale (par-
thromboembolism adoxical embolus)
5. Self assessment.
1. Disorders that predispose to thrombosis include all of the following, EXCEPT:
1. Pancreatic carcinoma
2. Pregnancy
3. Vitamin K deficiency
4. Sickle cell anemia
5. Severe burns
2. Each of the following conditions favors the development of thrombosis, EXCEPT:
1. Endothelial injury
2. Polycythemia
3. Stasis
4. Thrombocytopenia
5. Congestion
3. The development of endothelial-lined blood channels that reestablish blood flow through
a vascular thrombus is known as:
1. Collateral circulation
2. Recanalization
3. Organization
4. Hyalinization
5. Incapsulation
4. Pathologic lesions resulting from passive congestion include all of the following,
EXCEPT:
1. Nutmeg liver
2. Brown induration of the lungs
3. Cyanotic induration of the spleen
4. Strawberry gallbladder
5. Marantic thrombi in superficial veins
5. The initial step of the thrombus formation is:
1. Activation of thrombin
2. Development of fibrin plugs
3. Endothelial injury
4. Margination of leukocytes
5. Trapping of red cells
6. Pulmonary emboli may originate from all of the following sites, EXCEPT:
1. Deep leg veins
2. Inferior vena cava
3. Pelvic veins
4. Portal vein
5. Right atrial appendage
7. The forms of embolism include all of the following, EXCEPT:
1. Pulmonary thromboembolism
2. Fat embolism
3. Viral embolism
4. Bacterial embolism
5. Air embolism
8. Selective stain that is used to identify fat in the fat emboli syndrome is:
1. Sudan III
2. Tolluidin blue
3. Congo red
4. PAS reaction
5. Hematoxylin and eosin
9. The clinical effects of fat emboli are usually due to obstruction of the small vessels of:
1. Brain and kidney
2. Kidney and spleen
3. Liver and brain
4. Lung and spleen
5. Spleen and liver
10. The usual source of pulmonary emboli are:
1. Thrombi in the deep veins of the lower extremities
2. Thrombi in the veins of upper extremities
3. Thrombi in the vena porta
4. Thrombi in the left atrial appendage
5. Thrombi in the uterus arteries
11. The most common source of arterial thromboemboli is:
1. Cardiac thrombi
2. Aortic aneurysm
3. Pulmonary veins
4. Aortic atherosclerotic plaques
5. Iliac vein
12. White infarct results from the following condition:
1. Venous occlusion
2. Arterial occlusion
3. Loose tissue
4. Tissues with dual circulation
5. Previously congested with blood tissues
13. Red infarction is caused by all of the following events, EXCEPT:
1. Coronary artery thrombosis
2. Pulmonary embolism
3. Torsion of the testis
4. Thromboembolism of superior mesenteric artery
5. Portal vein thrombosis
14. Ischemic injury in the central nervous system results in:
3. Caseous necrosis
5. Fat necrosis
15. The type of necrosis most often caused by sudden vascular occlusion is:
1. Apoptosis
2. Caseous necrosis
3. Coagulation necrosis
4. Fat necrosis
16. Red infarct occurs in which of the following organs:
l. Lung
2. Heart
3. Spleen
4. Kidney
5. Lower extremity
17. Acute tubular necrosis develops in:
1. Amyloidosis
2. Acute glomerulonephritis
3. Kidney infarct
4. Systemic thromboembolism
5. Hypovolemic shock
18. White infarct commonly occurs in all organs, EXCEPT:
l. Lung
2. Spleen
3. Kidney
4. Heart
5. Brain
19. Shock is commonly associated with all of the following conditions, EXCEPT:
1. Escherichia coli sepsis
3. Cholera
4. Acute pancreatitis
5. Cerebral infarction
20. All the following disorders are associated with disseminated intravascular coagulation,
EXCEPT:
1. Infections
2. Neoplasms
3. Massive tissue injury
4. Malnutritions
5. Obstetric complications
ANSWERS
1 3 11 1
2 4 12 2
3 2 13 1
4 4 14 1
5 3 15 3
6 4 16 1
7 3 17 5
8 1 18 1
9 1 19 5
10 1 20 4
Class 7
Theme: INFLAMMATION. EXUDATIVE INFLAMMATION

1. Definition of inflammation.
2. Etiology.
3. Pathogenesis and morphogenesis of inflammation:
alteration, exudation, their mechanism:
a). Reaction of microcirculatory bed.
b). Formation of exudate and inflammatory cellular infiltrate.
Proliferation (cellular composition in the focus of inflammation).
4. Terminology and classification.
5. Exudative inflammation: its kinds, causes, localization, characteristic of
course, outcomes.
INFLAMMATION
Inflammation is defined as the vascular-mesenchymal response of living tis-
sues to injury caused by any agent. It is a bodys defense reaction in order to elimi-
nate, to limit the spread of injurious agent and to restore damaged tissue.
Causes. The agents causing inflammation may be as follows:
1. Physical agents (heat, cold, radiation, mechanical injury).
2. Toxic chemical agents (organic and inorganic poisons).
3. Microbiological agents (bacteria, viruses, parasites, fungi).
4. Immunological agents (cell-mediated, immune complex and antigen-
antibody reactions).
Clinicomorphological signs of inflammation. There are 5 main clinico-
morphological signs of inflammation: rubor (redness); tumor (swelling); calor (heat),
dolor (pain) and functio laesa (loss of function).
The word inflammation means burning. This nomenclature has its origin in
old times but now we know that burning is only one of the signs of inflammation.
The condition develops on the territory of histion.
Types of inflammation
There are 3 phases in inflammation: alteration, exudation and proliferation. The
first phase is alteration, degeneration and necrosis of the cells, tissue. The second
phase is exudation, formation of exudate.
According to the prevailing one of these phases, inflammation is classified into
2 groups. We distinguish exudative and proliferative inflammations.
Depending upon the defense capacity of the host and duration of the response,
inflammation can be classified as acute and chronic.
Exudative inflammation usually develops as acute inflammation; proliferative
inflammation develops as a chronic one.
Acute inflammation is of short duration and represents the early body reaction
and is usually followed by repair.
Chronic inflammation is of longer duration and occurs either after the causative
agent of acute inflammation persists for a long time, or the stimulus is such that it
induces chronic inflammation from the beginning.
Types of exudation. The appearance of escaped plasma determines the mor-
phological type of inflammation. These are:
1. Serous, when the fluid exudate resembles serum or is watery, e.g. pleural ef-
fusion in tuberculosis, blister formation in burns.
2. Fibrinous, when the fibrin content of the fluid exudate is high, e.g. in pneu-
mococcal and rheumatic pericarditis. Two types may be croupous and diphtheric fi-
brinous inflammation.
3. Purulent or suppurative exudate is a formation of creamy pus as seen in in-
fection with pyogenic bacteria, e.g. abscess, acute appendicitis, phlegmon.
4. Hemorrhagic, when there is vascular damage (severely increased permeabil-
ity), e.g. acute hemorrhagic pneumonia in influenza.
5. Catarrhal, when the surface inflammation of mucous epithelium produces
increased secretion of mucus, e.g. common cold.
6. Mixed.
Morphology of acute inflammation
Inflammation of an organ is usually named by adding the suffix itis to its
Latin name e.g. appendicitis, hepatitis, cholecystitis, meningitis, etc. A few morpho-
logic varieties of acute inflammation are described below:
1. Serous inflammation.
Serous inflammation is marked by the outpouring of a thin fluid that, depend-
ing on the size of injury, is derived from either the blood serum or the secretions of
mesothelial cells lining the peritoneal, pleural, and pericardial cavities.
The skin blister resulting from a burn or viral infections represents 1 large ac-
cumulation of serous fluid, either within or immediately beneath the epidermis of the
skin.
Serous exudate contains less than 2% of protein and the little number of cells
(neutrophils, macrophages, and desquamative epithelium).
Serous inflammation is located in serous membranes (polyserositis in rheu-
matic diseases, autointoxication uremia), in mucus membranes (serous rhinitis), in
skin (streptococcus infections, herpes, burn), seldom in internal organs (serous pneu-
monia).
Outcomes are favorable, because exudate resolves.
2. Fibrinous inflammation or pseudomembranous inflammation. With more
severe injuries and the resulting greater vascular permeability, larger molecules such
as fibrin pass through the vascular barrier. A fibrinous exudate develops when the
vascular leaks are large enough or there is a procoagulant stimulus in the interstitium
(e.g., cancer cells). A fibrinous exudate is characteristic of inflammation in body cav-
ities, such as the pericardium and pleura. Microscopically, fibrin appears as an eosin-
ophilic meshwork of threads, or sometimes as an amorphous coagulum. Fibrinous
exudates may be removed by fibrinolysis, and other debris by macrophages. This
process, called resolution, may restore normal tissue structure, but when the fibrin is
not removed it may stimulate the ingrowth of fibroblasts and blood vessels and thus
lead to scarring. Conversion of the fibrinous exudate to scar tissue organization with-
in the pericardial sac will lead either to opaque fibrous thickening of the pericardium
and epicardium in the area of exudation or, more often, to the development of fibrous
strands that bridge the pericardial space.
According to the type of epithelium on which the inflammatory process devel-
ops and the depth of necrosis there are two types of fibrinous inflammation: croupous
and diphtheric fibrinous inflammation. Usually croupous inflammation develops on
the columnar epithelium. In this case the fibrinous membranes unfix easily, without
any effort. Diphtheric fibrinous inflammation develops on the squamous or interme-
diate epithelium, when the fibrinous membranes unfix with difficulties.
3. Suppuration or purulent inflammation. There are several types of suppura-
tion: an abscess, phlegmon, furuncle, carbuncle, cellulitis, bacterial infections of the
blood.
When acute bacterial infection is accompanied by intense neutrophilic infiltrate
in the inflamed tissue, it results in tissue necrosis. A cavity is formed which is called
an abscess and contains purulent exudate or pus and the process of abscess formation
is known as suppuration. The bacteria which cause suppuration are called pyogenic.
Pus is creamy or opaque in appearance and is composed of numerous dead as well as
living neutrophils, some red cells, fragments of tissue debris and fibrin. In old pus,
macrophages and cholesterol crystals are also present. The wall of abscess is called
pyogenic membrane. An abscess may be discharged to the surface due to increased
pressure inside or may require drainage by the surgeon. Due to tissue destruction,
resolution does not occur but instead healing by fibrous scarring takes place.
Phlegmon is unbounded purulent inflammation in which pus spreads diffusely
between different components of tissue owing to fusion and tissue lysis. Phlegmon
frequently occurs along the muscular bands, tendons, fascias, vascular-nerve bands
and in subcutaneous fat. Two types of phlegmon have been described: soft and dense.
If purulent exudate appears in the human cavities t is called empyema.
Apostematous purulent inflammation is defined as formation of microabscesses
on the background of diffuse purulent inflammation. For instance, apostematous ne-
phritis, apostematous appendicitis.
Furuncle is an acute inflammation via hair follicles in the dermal tissues.
Carbuncle is seen in untreated diabetics and occurs as a located abscess in the
dermis and soft tissues of the neck.
Cellulitis. It is a diffuse inflammation of soft tissues resulting from spreading
effects of substances like hyaluronidase released by some bacteria.
Bacterial infections of the blood. This includes the following 3 conditions: bac-
teremia, septicemia, pyemia.
4. Hemorrhagic inflammation. Where the damage is severe, actual rupture of
all small blood vessels and severe increasing of their permeability occur, with hemor-
rhage the most striking feature (acute hemorrhagic pneumonia occasionally occurring
in fatal cases of influenza).
5. Putrefactive inflammation. Is associated with anaerobic bacteria and charac-
terized by numerous necroses.
6. Catarrhal inflammation. A surface inflammation of mucous membranes as-
sociated with greatly increased secretion of clear mucus. Later, polymorphs appear
(common cold and some forms of colitis). It can be acute and chronic; serous, fibrin-
ous and purulent.
The acute inflammatory process can culminate in one of the following 4 out-
comes: resolution, healing by scarring, progression to suppuration, progression to
chronic inflammation.
Resolution. This means complete return to normal tissue following acute in-
flammation. It occurs when tissue changes are slight and the cellular changes are re-
versible, e.g. resolution in lobar pneumonia.
Healing by scarring. This takes place when the tissue destruction in acute in-
flammation is extensive or that there is no tissue regeneration but actually there is
healing by fibrosis.
Progression to suppuration. When the pyogenic bacteria causing acute in-
flammation result in severe tissue necrosis, the process progresses to suppuration.
Initially, there is intense neutrophilic infiltration, subsequently, mixture of neutro-
phils, bacteria, fragments of necrotic tissue, cell debris and fibrin comprise pus which
is contained in a cavity to form an abscess. The abscess, if not drained, may get orga-
nized by dense fibrous tissue, and in time, get calcified.
Progression to chronic inflammation. Acute inflammation may progress to
chronic one in which the processes of inflammation and healing proceed side by side.
3. Class work.

167 Fibrinous pericarditis. Epicardium is covered with grey-brownish
masses of fibrin. As the outcome of the disease, the fibrin is exposed to the processes
of organization, adhesions appear between pericardium sheets. Sometimes the oblite-
ration of pericardium cavity with depositions of calcium is developed (so-called
stone heart).
194 Lobar pneumonia. All alveoli are filled with exudate of grayish col-
or, consisting of fibrin and leukocytes. The whole lobe is affected.
53-, Diphtheric inflammation of the intestine mucous membrane.
The wall of intestine is swollen, the mucous membrane is covered with grayish col-
ored membrane, that is closely connected with adjacent tissues.
48 Acute ppendicitis. Appendix (especially its top) is thickened due to
swelling. Serous coat is covered with grayish fibrin.
278-, , , Purulent meningitis. The pia-arachnoid mater is thickened
due to swelling, it is dim and is infiltrated with grayish colored pus.
190 Inflammation of the larynx. Mucous coat of larynx and trachea is
covered with grayish colored layer which is easily separated from adjacent tissues.
59 Fibrinous pericarditis. (hematoxylin and eosin staining). Study. Pay
attention to the fibrin (arrow) which covers the epicardium and is stained as homoge-
neous substance of pink color. There is arterial hyperemia, swelling, leukocyte infil-
tration in underlying tissues. Draw.
55- Lobar pneumonia (the stage of grey hepatization). (hematoxylin

and eosin staining). The lumen of alveoli is filled with mesh substances of fibrin (ar-
row) and leukocytes. Note the kind of inflammation.
60 Purulent nephritis. (hematoxylin and eosin staining). Find the foci of
purulent inflammation (arrow), determine the structure of exudate. Draw.
65 Catarrhal gastritis. (hematoxylin and eosin staining). Study. Mucous

coat of stomach is hyperemic, with swelling and leukocytes inflammatory infiltration.
There is exudate containing few neutrophilic leukocytes and desquamated epithelium
on the mucous coat surface (arrow). The submucous coat is swollen.
Sequence of inflammatory phases

Phases of inflammation Morphological characteristic
Alteration Dystrophy, necrosis
Exudation
Proliferation
Exudative inflammation
Kind of in- Structure of ex- Tissues that are damaged Causes Fate
flammation udates
1. Serous Serous fluid, pro- Epithelium, skin, mesothe- Viruses, Exudate re-
tein less than 2%, lium, parenchyma of vis- toxins, thermal solves
single cells ceral organs burns
2. Fibrinous
3. Purulent
4. Hemorrhagic
5. Catarrhal
6. Putrefactive
4. Clinical tasks.
1. A 53-year-old man suffered from chronic glomerulonephritis for 15 years, died of

chronic renal failure (uremia). At autopsy, brain edema, fibrinous coats on the mu-
cous membrane of the larynx, trachea, bronchi, stomach, and intestine were revealed.
The epicardium and pericardium were covered with fibrin. There was grayish-whitish
fluid in the pleural and abdominal cavities.
1. What kind of exudative inflammation occurred on the mucous membrane of
the trachea and bronchi?
2. What kind of exudative inflammation occurred in the large bowel?
3. What is the name of the changes revealed in epicardium and pericardium?
2. A 5-year-old child died of meningococcal meningitis. At autopsy, the gyri and

sulci of the brain were flattened; the pia-arachnoid mater was infiltrated with green-
ish-yellowish exudate.
1. What kind of inflammation occurred in pia-arachnoid mater of the brain?
2. What is the composition of exudate in this kind of inflammation?
3. What is the direct cause of the childs death?
3. A 38-year-old man who presented with croupous pneumonia had fluid in his
pleural cavity that was revealed by X-ray examination. On exploratory puncture,
greenish-yellowish fluid was revealed.
1. What complication occurred in this patient?
2. What is the name of the fluid revealed at puncture?
3. What is the composition of the fluid?
4. A 57-year-old man who had influenza developed bilateral focal pneumonia in the
lower lobes of the lungs. The patient died of pulmonary-cardiac failure. At autopsy, a
4 cm size cavity in the lower lobe of the left lung filled with greenish dull fluid was
found.
1. What is the name of the formation found in the left lung?
2. What does it contain?
3. What are the types of this formation?
5. A 56-year-old man was infected with anthrax after retail cuts of beef. At autopsy,
the gyri and sulci of the brain were flattened; the pia-arachnoid mater was red.
1. What type of exudative inflammation occurred in the pia mater?
2. What is the most important event in the morphogenesis of this inflammation
kind?
3. What is the direct cause of the patients death?
ANSWERS
1 1 2 3
Croupous inflamma- Diphtheric inflammation Fibrinous inflammation (Hairy
tion heart)
2 Purulent inflamma- There is a lot of neutrophils in Brain edema with dislocation syn-
tion exudate drome
3 Empyema of pleura Purulent exudate Fluid contains numerous neutro-
phils
4 Abscess Pus Chronic and acute abscess
5 Hemorrhagic Severe increase of vascular per- Brain edema
meability
5. Self assessment.
1. The inflammatory response leads to all of the following, EXCEPT:
1. Isolation of infected tissues
2. Inactivation of callsative agents
3. Neutralization of toxins
4. Removal of devitalized tissue debris
5. Obesity
2. Cell type that transforms into morphologically distinct cells capable of immunoglobulin
production is:
1. Neutrophils
2. Basophils
3. B-cells
4. T-cells
5. NK-cells
3. Major functions of macrophages are all of the following, EXCEPT:
1. Phagocyte function
2. IL-1- synthesizing function
3. Secretory function
4. Antibody-synthesizing function
5. Healing and repair function
4. Cells that are capable of phagocytosis of particulate matter include
1. Neutrophils, macrophages
2. Lymphocytes, mast cells
3. T-cells, NK-cells
4. Basophils, stem cells
5. Endothelial cells, plasma cells
5. Mediators of increased vascular permeability in acute inflammatory responses include
all of the following, EXCEPT:
1. Leukotriene E4
2. Complement complex C5b-9
3. Leukotriene C4
4. Bradykinin
5. Platelet-activating factor
6. Anti-inflammatory drugs such as aspirin and indomethacin (non-steroidal drugs) in-
hibit:
1. Lymphokine production
2. Lysosomal degradation
3. Leukotriene and prostaglandin production
4. Vasoactive amine release
5. Fibronectin production
7. Activation of Hageman factor leads to activation all of the following catalytic systems,
EXCEPT:
1. The complement system
2. P-450 (mixed-function oxidase system)
3. Kinin system
4. Fibrinolytic system
5. Coagulation system
8. Plasma factors to be released during inflammation are all of the following, EXCEPT:
1. Bradykinin
2. Membrane attack sequence
3. Cationic proteins
4. Thrombin
5. Plasmin
9. When cells degenerate at the site of injury, all of the following substances may be re-
leased, EXCEPT:
1. Lysosomal enzymes
2. Vasoactive amines
3. Cyclooxygenase
4. Kinins
5. NO
10. All of the following factors promote neutrophil immigration into tissues during acute
inflammatory responses, EXCEPT:
1. Leukotriene B4
2. Nitric oxide
3. Intercellular adhesion molecule-1
4. Complement fragment C5a
11. The adherence of neutrophils and monocytes to the vascular endothelium prior to
movement into the extravascular space is called:
1. Margination
2. Diapedesis
3. Pavementing
4. Emigration
5. Clotting
12. The unidirectional migration of leukocytes toward a target is referred to as:
1. Diapedesis
2. Chemotaxis
3. Opsonization
4. Endocytosis
5. Margination
13. The first cells arrived at the injured area in the inflammatory response are the follow-
ing:
1. Neutrophils
2. Fibroblasts
3. Lymphocytes
4. Macrophages
5. Erythrocytes
14. During the inflammatory response, the proper order of white cell events is:
1. Endothelial adherence, margination, phagocytosis, chemotaxis
2. Margination, leukodiapedesis, chemotaxis, phagocytosis
3. Margination, migration, chemotaxis, stasis
4. Stasis, leukodiapedesis, margination, phagocytosis
5. Leukodiapedesis, stasis, degranulation
15. The most common formation in the body cavities and the spinal fluid is:
1. Fibrinous inflammation
2. Serous inflammation
3. Catarrhal inflammation
4. Hemorrhagic inflammation
5. Granulomatous inflammation
16. Fibrinous pericarditis occurs in all diseases, EXCEPT:
1. Acute rheumatic fever
2. Systemic lupus erythematosus
3. Uremia
4. Atherosclerosis
5. Acute myocardial infarction
17. The inflammatory infiltrate associated with an acute bacterial bronchopneumonia
consists predominantly of the following cells:
1. Eosinophils
2. Lymphocytes
3. Monocytes/macrophages
4. Neutrophils
5. Plasma cells
18. Purulent inflammation is characterized by:
1. Neutrophil infiltration with tissue lysis
2. Fibrin deposition
3. Mucus production
4. Lymphocyte infiltration
5. Neutrophil infiltration
19. Acute inflammation includes all of the following types, EXCEPT:
1. Purulent
2. Fibrinous
3. Granulomatous
4. Serous
5. Catarrhal
20. Lobar pneumonia is an example of the following type of inflammation:
1. Purulent
2. Fibrinous
3. Serous
4. Catarrhal
5. Granulomatous
ANSWERS
1 5 11 3
2 3 12 2
3 4 13 1
4 1 14 2
5 2 15 2
6 3 16 4
7 2 17 4
8 3 18 1
9 3 19 3
10 2 20 2
Class 8
Theme: INFLAMMATION: PROLIFERATIVE INFLAMMATION
I. Study the questions:

1. Proliferative (productive) inflammation, its kinds, the causes, mechanism of
development, classification, morphological characteristics, outcomes.
2. Granulomatous inflammation, granulomatous diseases.
3. The causes, mechanisms of development, the morphological characteristics of
inflammation in tuberculosis, syphilis, leprosy, and scleroma.
4. The characteristics of granulomas in tuberculosis, syphilis, leprosy, and scle-
roma.
CHRONIC INFLAMMATION
Chronic inflammation is defined as prolonged process in which tissue destruc-
tion and inflammation occur at the same time.
Chronic inflammation can be caused by one of the following 3 ways:
1. Chronic inflammation following acute inflammation when the tissue de-
struction is extensive, or the bacteria survive and persist in small numbers at the site
of acute inflammation, e.g. in osteomyelitis, pneumonia terminating in lung abscess.
2. Recurrent attacks of acute inflammation when repeated bouts of acute in-
flammation culminate in chronicity of the process, e.g. in recurrent urinary tract in-
fection leading to chronic pyelonephritis, repeated acute infection of gall bladder
leading to chronic cholecystitis.
3. Chronic inflammation starting de novo when the infection with organisms
of low pathogenicity is chronic from the beginning, e.g. infection with Mycobacte-
rium tuberculosis.
Though there may be differences in chronic inflammatory response depending
upon the tissue involved and causative organisms, there are some basic similarities
amongst various types of chronic inflammation. These general features characterize
any chronic inflammation.
1. Mononuclear infiltration. Chronic inflammatory lesions are infiltrated by
mononuclear inflammatory cells like phagocytes and lymphoid cells. Phagocytes are
represented by circulating monocytes, tissue macrophages, epithelioid cells and
sometimes, multinucleated giant cells. The macrophages comprise the most important
cells in chronic inflammation.
2. Tissue destruction and necrosis. Tissue destruction and necrosis are common
in many chronic inflammatory lesions and are brought about by activated macro-
phages by release of a variety of biologically active substances.
3. Proliferative changes. As a result of necrosis, proliferation of small blood
vessels and fibroblasts is stimulated resulting in formation of inflammatory granula-
tion tissue. Eventually, healing by fibrosis and collagen laying takes place.
Main classifications of chronic inflammation

Conventionally, chronic inflammation is subdivided into 2 types.
1. Nonspecific, when the irritant substance produces a non-specific chronic in-
flammatory reaction with formation of granulation tissue and healing by fibrosis, e.g.
chronic osteomyelitis, chronic ulcer.
2. Specific, when the injurious agent causes a characteristic histological tissue
response, e.g. tuberculosis, leprosy, syphilis.
However, for a more descriptive classification, histological features are used
for classifying chronic inflammation into 3 corresponding types.
1. Chronic nonspecific interstitial inflammation. This is characterized by non-
specific inflammatory cell infiltration, e.g. chronic osteomyelitis, lung abscess. A var-
iant of this type of chronic inflammatory response is chronic suppurative inflamma-
tion in which infiltration by polymorphs and abscess formations are additional fea-
tures, e.g. actinomycosis. The inflammatory cell infiltration consists of lymphocytes,
monocytes, plasmocytes, eosinophils and other cells.
2. Chronic nonspecific interstitial inflammation with formation of polyps and
pointed condyloma. It occurs on the mucous membranes and in the areas at the border
between columnar and squamous epithelia.
Polyps are the end result of prolonged chronic irritation. Nasal, cervical, colo-
rectal polyps are common. Macroscopically they are gelatinous masses with smooth
and shining surface. Microscopically they are composed of loose edematous connec-
tive tissue containing some mucous glands and varying number of inflammatory cells
(lymphocytes, plasmocytes, eosinophils).
Condyloma is commonly located on the coronal sulcus on the penis or the per-
ineal area.
3. Chronic granulomatous inflammation. This is characterized by formation of
granulomas, e.g. tuberculosis, leprosy, syphilis, actinomycosis, sarcoidosis, etc.
Granuloma is defined as a circumscribed, tiny lesion, about 1 mm in diameter, com-
posed predominantly of collection of modified macrophages called epithelioid cells,
and rimmed at the periphery by lymphoid cells. The word granuloma is composed
of granule meaning circumscribed granule-like lesion, and -oma which is a suffix
commonly used for true tumors but here indicates inflammatory mass or collection of
macrophages. The epithelioid cells, so called because of their epithelial cell-like ap-
pearance, are modified macrophages which are somewhat elongated, having pale-
staining abundant cytoplasm, lightly-staining nucleus and the cell membrane of adja-
cent epithelioid cells is closely apposed. Besides the presence of epithelioid cells and
lymphoid cells, granulomas may have giant cells, necrosis and fibrosis. The giant
cells are formed by fusion of adjacent epithelioid cells or by internal nucleate division
without cytoplasmic division and may have 50100 nuclei. These nuclei may be ar-
ranged at the periphery like horse-shoe or ring or clustered at the two poles
(Langhans' giant cells), or they may be present centrally (foreign body giant cells).
The former are commonly seen in tuberculosis while the latter are common in foreign
body tissue reactions.
Necrosis may be a feature of some granulomatous conditions, e.g. central case-
ous necrosis of tuberculosis, so called because of cheese-like appearance and con-
sistency of necrosis.
Fibrosis is due to proliferation of fibroblasts at the periphery of granuloma.
The following two factors favour the formation of granulomas:
1. Presence of poorly digestible irritant which may be organisms like Mycobac-
terium tuberculosis, particles of talc, etc.
2. Presence of cell-mediated immunity to the irritant, implying thereby the role
of hypersensitivity in granulomatous inflammation.
A fully-developed tubercle is about 1 mm in diameter with central area of ca-
seous necrosis, surrounded by epithelioid cells and one to several multinucleated gi-
ant cells (commonly Langhans' type), surrounded at the periphery by lymphocytes
and bounded by fibroblasts and fibrous tissue.
Granulomatous inflammation is typical of reaction to poorly digestible agents
elicited by tuberculosis, leprosy, fungal infections, schistosomiasis, foreign particles,
etc.
Microscopical examination of the specific granuloma

In tuberculosis, the granuloma is referred to as a tubercle and is classically
characterized by the presence of central caseous necrosis surrounded by epithelioid
cells, lymphocytes, plasma cells and giant Langhans' cells. In contrast, caseous necro-
sis is rare in other granulomatous diseases.
The syphilitic granuloma is called gumma. Gumma consists of a central area of
fibrinoid or caseous necrosis surrounded by mononuclear inflammatory cells, mostly
plasma cells, lymphocytes, epithelioid cells, and seldom-giant Langhans cells. There
is granulation tissue and endovasculitis around gumma.
In tuberculoid leprosy, the epidermis contains confluent granulomas composed
of macrophages, plasma cells, and leprous Virchows cells. Large foamy macrophag-
es with fatty vacuoles containing leprous mycobacteria are referred to as leprous Vir-
chow's cells (or leprosy cells).
In rhinoscleroma of the nose, the granuloma (scleroma) consists of the plasma
cells, epithelioid cells, lymphocytes, and hyaline spheres. Large macrophages with
light cytoplasm containing Klebsiella Rhinoscleromatis are called Mikulicz's cells,
sclerosis and hyalinosis take place.
Microscopical examination of the nonspecific granulomas
Proliferative inflammation around echinococcus of the liver. The area of the
liver tissue with destructive pink color shiny chitinous membrane and surrounded ne-
crotic tissue are seen. In peripheral areas, crowded lymphocytes, plasma cells, fibro-
blasts and single foreign body giant cells can be found. There is fibrous capsule on
the periphery of granuloma.
Sarcoidosis. The tissue contains granulomas composed of epithelioid macro-
phages and only a few lymphocytes and giant cells. There is no central necrosis.
The outcomes of chronic inflammation depend on the type of inflammation,

morphofunctional characteristics of the definite organ or tissue, where inflammation
develops. Frequently sclerosis and hyalinosis may develop.
3. Class work.

281. Cysticercosis of brain. On the surface of the brain hemispheres and
in the depth of grey and white matter of the brain, a lot of cysticerci of armed tape-
worm are visible.
207. Miliary tuberculosis of the lungs. Pay attention to the character of
distribution and amount of tuberculous tubercles. Note the most likely character of
tissue reaction.
210- Acute cavernous tuberculosis of lungs. Point out the localization
of the process. Describe the appearance of the lung when cut. Pay attention to the
state of the cavity and surrounding pulmonary tissue.
164. Syphilitic mesaortitis Note the characteristic localization of the aor-
tic injury, the change of its lumen diameter, and also the gross appearance of the in-
ternal coat surface. Name the most likely complications.

71. Miliary tuberculosis of lungs. Hematoxylin and eosin st. There is a
specimen of lung tissue with multiple confluent epithelioid cellular granulomas in the
microslide. In the center of the granuloma the focus of caseous necrosis is present.
Study cellular structure of granulomas (it is necessary to find epithelioid cells, lym-
phocytes, giant Langhans cells and to note the placing of these cells in the granulo-
ma).
Granuloma
Giant cell
77. Syphilitic mesaortitis. Stained with hematoxylin and eosin (first cut
Figure A). In the middle and external coat of the vessel the gummous infiltration is
seen (shown by arrow). It consists of plasma cells, lymphocytes and fibroblasts with
single Langhans giant cells.
In the middle coat stained with orcein for visualization of elastic fibers (second
cut Figure B), foci of destroyed elastic fibers are visible (shown by arrow). Draw.
A B
78-. Syphilitic gumma of the liver. Stained with hematoxylin and eosin.
There is a large syphilitic granuloma in liver tissue with necrotic focus in the center
surrounded by lymphplasmocytic infiltrate containing fibroblasts. Macrophages, epi-
thelioid cells and single Langhans cells may be seen. There is proliferation of fibro-
blasts and connective tissue growth with the formation of capsule like structure which
has different sized blood vessels with inflammation (productive endovasculitis).
Syphilitic granulo-
ma
79-. Scleroma of the superior respiratory pathways. Hematoxylin and

eosin st. There are specimens of nose mucous membrane in the preparation. There is
inflammation in the subepithelial layer. Describe the type of inflammation. Find hya-
line spheres (shown by yellow arrow) and Mikulicz cells (shown by black arrow).
What is the etiology of this disease? Draw.
III. Complete the table:
Stages of granuloma formation

Stage Morphological changes
Young granuloma Accumulation of monocytes in the area of injury
Proliferative inflammation with specific granuloma formation

Agent, name of disease Stages or forms, tissue reaction
Treponema pallidum, Syphilis Primary (chancre) infiltrative-productive
4. Clinical tasks.
1. A 36-year-old patient died of progressive pulmonary-cardiac failure. At autopsy,
multiple fine whitish tubercles 1-2 mm in size were found in tissues of both lungs.
The histological examination revealed necrosis in the center of tubercles (granulo-
mas), epithelioid cells with single Langhans cells were found around the necrosis,
and lymphocytes were situated on the periphery of granuloma.
1. What is the most likely diagnose?
2. What kind of inflammation is the morphological base of this disease?
3. What is the phase of this disease?
2. The clinical examination of a 28-year-old woman revealed bulging of aortic arch

wall. Wassermann test was positive (RW).
2. What is the name of the changes in the aorta?
3. What microscopical changes can be found in the wall of aorta?
3. On postmortem examination of a 37-year-old man who suffered from syphilis,

nodules (0.3-2 cm in size) were found in different organs (bones, liver, brain, skin).
Histologically, the structure of the nodules had the following features: the focus of
caseous necrosis in the center; surrounding zone was presented by lymphocytes,
plasma cells, fibroblasts and connective tissue growth with blood vessels which were
characterized by endovasculitis.
1. What is the name of the found nodules?
2. What period of syphilis is characterized by the formation of such nodules?
3. What other cells can be found in these nodules?
4. On postmortem examination of a 49-year-old man who suffered from leprosy dif-

fuse skin lesions with the destruction of the appendages of skin, leprous neuritis,
granulomas in liver, spleen, bone marrow, lymph nodes, mucous membrane of tra-
chea and bronchi were found.
1. What form of leprosy was revealed in the patient?
2. What is the name of the leprous granuloma?
3. What is the microscopical structure of leprous granuloma?
5. On examination of the trachea biopsy of a 26-year-old man, granulomas com-

posed of Mikulicz cells, lymphocytes, and plasma cells were found.
2. Give the characteristics of Mikulicz cells.
3. What morphological changes will develop as a consequence of this granulom-
atous inflammation?
ANSWERS
1 1 2 3
Tuberculosis Granulomatous inflam- Acute phase of disease
mation
2 Syphilis Aneurism Gummous infiltrate is situated mainly in the
middle layer of aorta; destruction of elastic
fibers of aorta (syphilitic mesaortitis)
3 Gumma (syphi- Tertiary period Giant Langhans cells, epithelioid cells, macro-
litic granuloma) phages
4 Lepromatous Leproma Leproma consists of macrophages (Virchows
leprosy cells), epithelioid cells, giant cells, plasma
cells, fibroblasts
5 Rhinoscleroma Mikulicz cells are large Sclerosis
macrophages with single
nuclei and vacuolated
cytoplasm.
5. Self assessment.
1. The most reliable histopathologic evidence of chronicity in an inflammatory process in
organs is:
1. Presence of hemorrhages
2. Leucocytic infiltrate
3. Blood vessels destruction
4. Interstitial fibrosis
5. Councilman's bodies
2. Chronic inflammation is characterized by:
1. Infiltration with mononuclear cell including macrophages, lymphocytes, and plasma cells
2. Tissue destruction
3. Healing by connective tissue growth with angiogenesis and fibrosis
4. All of above
5. None of above
3. The possible causes of chronicity of inflammation are all of the following, EXCEPT:
1. Persistent infections by certain microorganisms
2. Prolonged exposure to potentially toxic agents, either exogenous or endogenous
3. Autoimunity
4. Complete phagocytosis
5. Resistance of the etiologic agent
4. Recruitment of monocytes from the circulation in chronic inflammation is stimulated
by of all of the following, EXCEPT:
l. IL-11
2. CSF-GC
3. Oncogenes
4. Fragments of the destroyed collagen and fibronectin
5. Fibrinopeptides
5. Products released by the activated macrophages that lead to tissue injury, include all of
the following, EXCEPT:
1. Fibrogenic cytokines
2. Toxic oxygen metabolites
3. Collagenases
4. Neutrophile chemotactive factors
5. Elastase
6. A large aggregate of epithelioid cells is seen in a microscopic section of an ovary re-
moved at surgery. Your diagnosis is:
1. Granulation tissue
2. Pyogenic granuloma
3. Granulosa cell tumor
4. Granulocytosis
5. Granuloma
7. The miliary lung tuberculosis is characterized by which of the following types of in-
flammation:
1. Granulomatous
2. Serous
3. Fibrinous
4. Supurative
5. Hemorrhagic
8. What type of necrosis can be found in tuberculous granuloma?
1. Coagulation necrosis
3. Caseous necrosis
4. Enzymatic fat necrosis
9. Typical tuberculous granuloma is characterized by all of the following, EXCEPT:
1. Plasma cells
2. Area of central necrosis
3. Epithelioid cells
4. Langhans-type giant cells
5. Lymphocytes
10. The granuloma in primary tuberculosis is composed predominantly of:
1. Fibroblasts
3. Eosinophils
4. Plasma cells
5. Neutrophils
11. What cells play the most important role in chronic tuberculous inflammation?
1. Macrophages
2. Leucocytes
3. Eosinophils
4. Erythrocytes
5. Plasma cells
12. On gross inspection, syphilitic gumma (granuloma in tertiary syphilis) is character-
ized by all of the following features, EXCEPT:
1. White-gray
2. Rubbery
3. Solitary
4. Red-brown
5. Tumor- like
13. The pathologic changes of vasa vasorum of aorta in syphilitic mesaortitis are charac-
terized by which of the the following:
1. Migratory thrombophlebitis
2. Productive vasculitis (obliterative endoarteritis)
3. Thromboangitis obliterans
4. Necrotizing arteriolitis
5. Thrombotic microangiopathy
14. The medial destruction of aorta in tertiary syphilis may lead to which of the following:
1. Aneurismal dilatation of the aorta
2. Marfan's syndrome
3. Atherosclerosis
4. Takayasu's arteritis
5. Giant cell arteritis
15. Syphilis granuloma is also called:
1. Fibroma
2. Gumma
3. Tuberculoma
4. Leproma
5. Hepatoma
16. Typical syphilis granuloma is characterized by all of the following, EXCEPT:
1. Area of central necrosis
2. Plasma cell infiltrate
3. Lymphocyte infiltrate
4. Productive vasculitis
5. Platelet infiltrate
17. What cells are known as "lepra cells" in lepromatous leprosy?
1. Foam cells filled with lipid droplets
2. Macrophages filled with masses of acid-fast bacilli
3. Epitheliod cells
4. Langhans-type giant cells
5. Schwann's cells
18. The granuloma in sarcoidosis is composed predominantly of:
1. Monocytes/macrophages
2. Neutrophils
3. Eosinophils
4. Plasma cells
5. Lymphocytes/fibroblasts
19. Sarcoidisis development is associated with:
1. Mycobacterium leprae
2. Mycobacterium tuberculosis
3. Treponema pallidum
4. Gram-negative bacillis
5. Unknown
20. What type of necrosis can be found in sarcoid granuloma?
2. Caseous necrosis
4. Enzymatic fat necrosis
ANSWERS
1 4 11 1
2 4 12 4
3 4 13 2
4 3 14 1
5 1 15 2
6 5 16 5
7 1 17 2
8 3 18 1
9 1 19 5
10 2 20 5
Class 9
Theme: IMMUNOPATHOLOGICAL PROCESSES

1. Immune reactions and the morphology of immunogenesis. Organs and cells
providing immune reactions; mechanisms of immune reactions.
2. Changes in the thymus, arising in disorders of immunogenesis.
a) accidental and age involution
b) hyperplasia
c) hypoplasia
3. Changes in peripheral lymphoid tissue on antigenic stimulation. Changes in
the central and peripheral organs of immunogenesis.
4. Local allergic reactions.
Reactions of hypersensitivity:
a) Immediate type, the mechanism of its development
b) Delayed type, the mechanism of its development
c) Transplantation immunity
5. Autoimmune diseases: classification, mechanisms of development.
6. Immunodeficiency. Acquired and congenital immunodeficiency diseases.
AIDS.
IMMUNOPATHOLOGICAL PROCESSES
Immunopathological processes are pathological states which are associated
with disturbances of lymphoid tissue structure and function.
THYMUS
Thymus is the central organ regulating of immune system. In disturbances of
immunogenesis usually the following processes and pathology are seen in the thy-
mus.
1. Accidental thymus transformation (involution), that is reduction in the size
and mass due to thymocytes migration to the peripheral immune organs and blood as
well as due to their partial decomposition and engulfment by macrophages (this is
called apoptosis).
According to T. Ivanovskaya (1976), accidental evolution consists of 5 stages.
Stage 1 holey clearing accumulation of lymphocytes around the macro-
phages. It occurs in the cortex.
Stage 2 transition of the lymphocytes from the cortex to the medullar sub-
stance. The boundary between the layers is either poorly seen or not seen at all.
Stage 3 layer inversion, when the cortex layer looks light, and medullar
layer looks dark as a result of transition of lymphocytes from the cortex to the medul-
lar substance.
Stage 4 reduction in the lymphocyte amount in the both layers, reticular
stroma growth.
Stage 5 collapse and sclerosis of the thymus lobe and lobe atrophy.
Accidental transformation more often occurs in the newborn suffering from
stress factors. The more powerful the stimulus, the more pronounced the degree of
involution. Accidental involution occurs in infections, intoxications, in children born
from sick mothers. The process is reversible. Elimination of pathological agent re-
sults in thymus normalization.
2. Thymus hyperplasia (thymolymphatic state, thymomegaly). The weight and
the size of thymus are considerably increased. Microscopic examination reveals a
large number of immature lobules (zones are not distinct). The density of the thymo-
cytes is high. If this condition is accompanied by hypoplasia of adrenal and sexual
glands as well as narrowing of the aorta and arteries, this pathological process is
called thymo-lymphatic state.
Sudden death syndrome (crib death) may occur in thymomegaly, it results from
insufficiency of T-lymphocytes of the cortex and medullar substance of the adrenal
glands.
3. Thymus hypoplasia is characterized by absence of lobule division into corti-
cal and medullar substance, poor development of reticuloepithelial component re-
sponsible for hormonal function, as well as lymphocyte component. As a rule thymus
hypoplasia is typical for congenital immune deficiency.
4. Aplasia total congenital lack of organ or its part.
5. Agenesis congenital disorder which is characterized by absence of thymus
germ.
6. Dysplasia of thymus means morphological structure disorders: there is no
cortex and medulla in lobules, the boundary between lobules is poorly seen, etc.
Thymus hypoplasia, aplasia, agenesis and dysplasia are congenital disturb-
ances.
7. Thymus hyperplasia with formation of lymphoid follicles.
CHANGES IN LYMPHOID TISSUE ON ANTIGEN STIMULATION

In the bone marrow firstly hyperplasia of B-lymphocytes is observed, and then
it becomes empty, as a result of increased transition of lymphocytes.
On antigen stimulation the morphologic processes developing in lymph nodes
and spleen of a healthy person and sick person are similar. Nevertheless they differ
by the quantity of the involved into pathological process cells, as well as by the char-
acter and grade of immune inflammatory reactions.
These changes are characterized by macrophage reactions; hyperplasia of B-
lymphocytes followed by their transformation into plasma cells.
The number of plasma cells shows the intensity of immunogenesis and corre-
sponds to the level of antibodies production.
Lymph nodes are: hyperplastic, edematous; follicular centers are pale (germi-
nal centers are enlarged), contain numerous blasts and macrophages; macrophage ag-
gregations are seen; there are a lot of plasma cells and macrophages in sinuses.
If cellular immune reaction develops in response to antigen the following mor-
phologic changes occur: proliferation of sensitized T-lymphocytes, enlargement of T-
dependent areas in lymph nodes (paracortical zones).
HYPERSENSITIVITY REACTION
A state of balance in the immune response (humoral or cell-mediated) is essen-
tial for protection against endogenous and exogenous antigens. Hypersensitivity is
defined as a state of exaggerated immune response to an antigen. The lesions of hy-
persensitivity (immunologic tissue injury) are produced due to interaction between
antigen and product of the immune response.
Depending upon the rapidity and duration of the immune response, four dis-
tinct forms of hypersensitivity reactions are recognized:
Hypersensitivity of immediate type. Immediate type of hypersensitivity is
further of three types type I, II and III.
Immediate hypersensitivity reaction morphologically manifests by the picture
of acute immune inflammation which develops rapidly, alteration and exudation stag-
es prevail, and proliferation increases slowly. The vessels and connective tissues are
involved first. Alteration manifests by mucoid, fibrinoid swelling and fibrinoid ne-
crosis. The exudate is either fibrinous or fibrino-hemorrhagic. Acute immune in-
flammation is observed in some forms of leprosy and syphilis. It is responsible for
vascular reaction in lupus erythematosus, glomerulonephritis, and nodular periarteri-
tis.
Hypersensitivity of delayed type. Morphologically it manifests by chronic
immune inflammation characterized by lymphocyte-macrophage infiltration. When
the lymphocyte-macrophage infiltration accompanied by vascular plasmorrhagic and
degenerative processes is seen the conclusion of immune inflammation can be made.
This condition occurs in autoimmune diseases, tuberculosis, brucellosis, dermatitis.
Type I reaction: Immediate type in which on administration (
, ) of antigens, the
reaction occurs immediately (within seconds to minutes). Immune response in this
type is mediated mainly by humoral antibodies.
Type II reaction: antibody-mediated cytotoxicity. In this type, antibody reacts
with a normal or altered cell-surface component, leading to subsequent destruction or
inactivation of the target cell.
Type III reaction: immune complex disease. In this type of reaction, circulat-
ing antigenantibody (immune) complexes (which normally are removed by the re-
ticuloendothelial system) are deposited in tissues, leading to complement activation
and further tissue injury. Immune complexes may also develop in situ (i.e., antibodies
are directed against antigens that are endogenous to the tissues or have been planted
there), thus triggering localized tissue damage.
Type IV reaction: cell-mediated hypersensitivity. Cell-mediated hypersensitiv-
ity reactions do not require the presence of antibody and, characteristically, are de-
layed anywhere from about 24 hours to 2 weeks. Three interrelated mechanisms are
recognized, all of which involve activated T-cells. Two types of cells take part in this
reaction. They are sensitized lymphocytes and macrophages. Granulomatosis is the
morphological manifestation of delayed hypersensitivity reaction.
Reaction of transplant rejection resembles slow hypersensitivity reaction.
Transplant antigens induce the production of antibodies and sensitized lymphocytes
which infiltrate the transplant.
Microscopically, lymphohistiocyte infiltration is observed in the transplant.
Cellular infiltration causes the disturbance of blood circulation and edema; as a result
degenerations and necrosis of transplant develop. Neutrophils and macrophages ap-
pear in the transplant. Enzymatic destruction of the transplant begins which is fol-
lowed by its rejection.
AUTOIMMUNE DISEASES
Immunologic tolerance and autoimmunity. An immune response generated
against self antigens is an aberrancy that implies the loss of immunologic ability to
distinguish self and alien antigens. The normal status of immunologic unresponsive-
ness to self antigens is termed tolerance. Tolerance probably represents an active
process involving continuous generation of cellular and humoral inhibitory regula-
tors. Loss of tolerance to self antigen is referred to as autoimmunity. The mecha-
nisms by which tolerance is generated and lost are poorly understood. Theories of
autoimmunity include:
1. Recognition of previously hidden (physiological isolation) or sequestered
antigen.
2. Diminution of suppressor T-cell function.
3. Increase in helper T-cell activity.
4. T-cell-independent polyclonal B-cell activation by complex antigens.
5. Modification of self antigens by drugs or microorganisms.
6. Cross-reactivity between autologous antigens and microbial antigens.
Autoimmune diseases are those occurring as a result of the reaction of autoan-
tibodies and sensitized lymphocytes against normal antigens of the own tissue. The
causes of autoimmune diseases are not clearly known. Chronic viral infections, radia-
tion and genetic factors may be responsible for them.
In the pathogenesis of autoimmune diseases the following factors are distin-
guished:
predisposing (HLA genes, hormonal background, genetically dependent fea-
tures of the target cells);
initiating (viral and bacterial infections, exposure of immune system and tar-
get organs to chemical and physical factors);
contributing (dysfunction of immune system, T-lymphocyte suppressor ac-
tivity).
In the pathogenesis 2 mechanisms can be distinguished; therefore all the auto-
immune diseases can be divided into 2 groups.
Group 1. Organ specific diseases. They are characterized by disturbance of
physiological isolation of organs and tissues due to absence of immune tolerance.
Lymphohistiocyte infiltration occurs in the tissues (like in delayed hypersensitivity
reaction). The main organ specific diseases are:
1. Endocrine glands:
Hashimoto's (autoimmune) thyroiditis.
Graves' disease.
Insulin-dependent diabetes mellitus.
Idiopathic Addison's disease.
2. Alimentary tract:
Autoimmune atrophic gastritis in pernicious anemia.
Ulcerative colitis.
Crohn's disease.
3. Blood cells:
Autoimmune hemolytic anemia.
Autoimmune thrombocytopenia.
4. Others:
Myasthenia gravis.
Autoimmune orchitis.
Autoimmune encephalomyelitis.
Goodpasture's syndrome.
Primary biliary cirrhosis.
Chronic active hepatitis.
Membranous glomerulonephritis.
Autoimmune skin diseases.
Group 2. Organ non-specific diseases. Primary disturbances in the immune
system causing the loss of ability to distinguish own and foreign antigens, they
are:
Systemic lupus erythematosus.
Rheumatoid arthritis.
Scleroderma (Progressive systemic sclerosis).
Polymyositis-Dermatomyositis.
Polyarteritis nodosa (PAN).
Sjogren's syndrome.
Reiter's syndrome.
Mixed connective tissue disease.
The diseases with autoimmune disturbances. In these diseases antigenic proper-
ties of the tissues are changed, that causes immune reaction development. Autoim-
munization is responsible not for the beginning but the progress of the disease as au-
toimmune antibodies appear during the disease. It is observed in glomerulonephritis,
hepatitis, chronic gastritis, burn disease, rheumatism, liver cirrhosis.
IMMUNODEFICIENCY SYNDROMES (IDS)
Immune deficiency syndromes result from immune system insufficiency.
All immune deficiencies are divided into 2 groups: primary or congenital im-
mune deficiencies and secondary or acquired immune deficiencies.
Primary IDS may be understood as primary defects in development of the im-
mune system. Secondary ones result from diseases or drugs that affect immune sys-
tem.
Primary IDS may be classified into the following 4 general groups depending
on the stage in development at which the defect occurs:
T-cell deficiencies;
B-cell deficiencies;
Combined (T-, B-cell) deficiencies;
Deficiency in inflammatory cells (agranulocytosis).
T-cell deficiencies manifests by agenesis, hypoplasia of the thymus and T-
dependent zones of the immune system. They are inherited according to autosomal
dominant type, e.g. MacCusic syndrome. Except for the pathology of thymus and
primary lymphatic tissue, defects of development occur.
DiGeorge syndrome is a selective deficiency of T-cells. This lack results from
failure of the third and fourth pharyngeal pouches to develop and become thymus and
parathyroid glands. DiGeorge syndrome is thought to be the result of an early intrau-
terine growth defect. It is not genetically linked. Affected infants have total absence
of T-cell immunity, in association with hypocalcemia and tetany. All lymphocytes are
B-cells. Plasma cells are present in normal numbers. T-cell areas, such as paracortical
areas of lymph nodes and periarteriolar sheaths are depressed.
Chronic mucocutaneous candidiasis is a selective defect of T-cell immunity
characterized by recurrent candidal infections involving the skin and mucous mem-
branes. The remainder of T-cell functions are intact, as is B-cell immunity. The de-
fect may be inherited as an autosomal recessive gene. Chronic mucocutaneous can-
didiasis is associated with endocrinopathies. Hypoparathyroidism is most common.
Addison's disease, hypothyroidism, diabetes mellitus, and pernicious anemia are also
seen. This association suggests a multiorgan endocrinopathy with selective thymic
dysfunction.
B-cell deficiencies. This type of inheritance is connected with X-chromosome,
e.g. agammaglobulinemia Bruton's syndrome. The thymus is preserved. B-zones in
the peripheral lymphatic organs are absent. Immunoglobulins synthesis is absent.
Bruton's (X-Iinked) agammaglobulinemia
In 1952, Bruton described an X-linked deficiency immunoglobulin production.
These patients suffered from recurrent bacteria-related bronchitis, otitis, and skin in-
fections. Infections usually began around the 6th month of life, as circulating maternal
antibodies in the infants subsided. All immunoglobulins were either markedly de-
creased or absent. Circulating mature B-cells were also absent.
It is now recognized that pre-B-cells are present in patients with Bruton's
agammaglobulinemia, and there seems to be a defect in the B-cell maturation se-
quence. Morphologically, there are no germinal centers in lymph nodes, the spleen,
and the tonsils. Plasma cells are absent.
Transient hypogammaglobulinemia of infancy is characterized by diminished
levels of immunoglobulin but the ability to produce certain antibody remains. The
disorder appears to be related to an abnormally long delay in the production of serum
immunoglobulin. (Maternal antibodies normally decline in the infant over the first 6
months of life.) Defects in helper T-cell function are thought to be responsible.
Common variable immunodeficiency is a somewhat poorly defined entity char-
acterized by hypogammaglobulinemia despite normal numbers of circulating B-cells.
In most cases, there is no clear-cut genetic predisposition. Patients range in age from
very young to elderly, although young adults are most commonly affected.
Selective IgA deficiency is the most common immunodeficiency disorder, oc-
curring in about 1 in 700 people. Serum IgA levels are low, but the numbers of circu-
lating IgA-cells are normal. However, these IgA-cells possess an immature pheno-
type that coexpresses IgD and IgM. Thus, the defect seems to be in the maturation of
IgA-bearing cells. Similar selective deficiencies in IgM are reported but rare.
Combined syndromes insufficiency of cellular and humoral immunity (T-,
B-cell insufficiency). This is inherited according to autosomal-recessive type, e.g.
Glanzmann-Riniker syndrome (agammaglobulinemia of Swiss type); severe com-
bined immunodeficiency (SCID); hypoplasia of thymus and peripheral lymphatic tis-
sue.
Severe combined immunodeficiency (SCID) is a severe disorder characterized
by nearly total absence of both T-cell and B-cell immunity. Infants present early with
recurrent opportunistic infections. SCID may be transmitted as either an X-linked or
autosomal recessive way.
Morphologically, there is a virtual absence of lymphoid tissue in the form of
lymph nodes, spleen, and tonsils. The thymus gland fails to descend from the neck
into the mediastinum and lacks lymphoid cells and Hassall's corpuscles.
These patients appear to have a stem-cell defect; deficiency in the enyzme
adenosine deaminase (ADA) is found in the cells of many patients with the autosomal
recessive form of SCID. ADA converts adenosine to inosine, or deoxyadenosine to
deoxyinosine. Without this enzyme, there is an accumulation of adenosine, deoxy-
adenosine, and deoxyadenosine triphosphate (dATP). This latter compound inhibits
ribonucleotide reductase, causing depletion of deoxyribonucleotide triphosphates and
abnormal lymphocyte function. SCID with ADA deficiency may be diagnosed prena-
tally by amniocentesis.
Secondary deficiencies occur after complete development of the immune sys-
tem. Some of these are secondary to immunosuppressive therapy, e.g. in tumors, au-
toimmune diseases, glomerulonephritis, etc. Chronic virus infections and HIV (hu-
man immunodeficiency virus) may cause secondary deficiencies. (See AIDS).
3. Class work.

194, 195. Lobar pneumonia (early consolidation stage) is an example
of hypersensitivity reaction of immediate type with fibrinous inflammation occur-
rence.
52-, Necrosis of Peyer's patches in typhoid fever represents hyper-
sensitivity reaction of immediate type. In Peyers patches, necrosis with ulcer for-
mation occurs.
103 Tuberculosis of the kidney is an example of hypersensitivity reac-
tion of delayed type with granuloma formation and tissue necrosis.

71. Miliary tuberculosis of the lungs (hematoxylin and eosin staining) is
an example of hypersensitivity reaction of delayed type. Find granulomas (see class
8). In the center of granuloma the focus of caseous necrosis is present. Study cellu-
lar structure of the granulomas (it is necessary to find epithelioid cells, lymphocytes,
giant Langhans cells, note the placing of these cells in the granulomas).
49 Hashimotos goitre (hematoxylin and eosin staining). Pay attention to
the atrophy of thyroid parenchyma and cellular infiltration of tissue with lymphoid
follicles formation (arrow). Determine the character of diffuse cellular infiltration;
find lymphocytes, plasmatic and reticular cells. What cells dominate in the infiltrate?
What is their action on the follicle epithelium? Draw.
135 Hypoplasia of spleen in AIDS (hematoxylin and eosin staining).

Find and draw the areas of spleen pulp containing lymphatic follicles without germi-
nal centers.
55-a Lobar pneumonia (grey hepatisation stage) (hematoxylin and eo-

sin staining) there are leucocytes and strands of fibrin in alveoli (see class 7).
147 Tuberculosis of thyroid gland (hematoxylin and eosin staining) is an
example of hypersensitivity of delayed type. Find granulomas (arrow), describe their
cellular structure.
III. Fill in the tables:

Types of local allergic reactions
Type of reaction The mechanism of development Value
Type I: anaphylac- During the first contact of the host with the antigen, sensitiza- Systemic and
tic (atopic) reaction takes place; during the second contact with the same anti- local anaphy-
tion gen degranulation of mast cells-basophils occurs; the released laxis
granules contain important chemicals and enzymes with proin-
flammatory properties
Autoimmune diseases, their classification

Group of diseases The name of disease Pathomorphogenesis Outcomes
Organ specific diseases Hashimoto`s goitre Caused by disturbance of Hypothyroidism
physiological isolation
4. Clinical tasks.
1. A 3-year-old child presented with significant developmental lagging. Clinical ex-

amination revealed hypoplasia of thymus and peripheral lymphoid tissue, hypoplasia
of spleen. Telangiectasia of bulbar conjunctiva and ataxia were diagnosed. The child
had recurrent pneumonia on the background of immunoglobulin insufficiency.
1. What kind of immunodeficiency occurred?
2. Is it primary or secondary?
3. What is the cause of ataxia?
2. A 2-year-old child who suffered from frequent infectious diseases underwent bi-
opsy of the lymph node. On examination of the biopsy, the B-dependent zone and
plasma cell lines were absent. T-cellular zones were present.
3. What is the most likely outcome of this disease?
3. On postmortem examination of an infant who died of tetany that resulted in acute
cardiopulmonary insufficiency, the thymus and parathyroid gland as well as T-
lymphocytes were absent.
3. What is the reason of death from tetany?
4. A 60-year-old woman suffering from chronic myeloleukemia, reports that she has
frequent inflammatory diseases of respiratory system and purulent skin infections. On
examination of bone marrow, the hyperplasia of tumor myelocytes with the lack of
immunoglobulin producing lymphocytes which resulted in humoral immunity insuf-
ficiency was identified.
1. What syndrome occurred in the patient?
2. What are the outcomes of this pathology?
3. Deficiency of what cells can be diagnosed in blood test?
5. An 18-year-old man who had purulent tonsillitis after 3 months developed an en-
largement of the submaxillary lymph node. On palpation, the lymph node was round,
dense, 2 cm in diameter, not adherent to the adjacent tissues. The microscopical ex-
amination of its biopsy revealed hyperplasia, hyperemia, edema, numerous active
macrophages in follicular centers; in the medullar layer there were numerous plas-
moblasts and plasma cells.
1. What reaction was the result of microorganism invasion of the regional lymph
nodes?
2. What is the meaning of plasmacyte-macrophage transformation activity?
3. What is the outcome of this process?
ANSWERS
1 1 2 3
The patient has combined immuno- Primary immunodeficiency of T Underdevelopment
deficiency syndrome (ataxia telangi- and B lymphocytes of cerebellum
ectasia)
2 Bruton's (X-Iinked) agammaglobu- Primary immunodeficiency of B Purulent infections
linemia lymphocytes of autoimmune
diseases
3 Agenesia or aplasia of thymus (Di- Primary immunodeficiency of T Absence of para-
George syndrome) lymphocytes thyroid gland
4 Secondary immunodeficiency syn- Purulent infections, frequent B-lymphocytes
drom acute attacks of chronic diseas- and plasma cells
es, sepsis
5 Plasmacyte-macrophage reaction, It reflects the intensity of im- Recovery
immune response mune response, i.e. antibody
production level
5. Self assessment.
1. Disorders of the immune system include all of the following, EXCEPT:
1. Hyalinosis
2. Hypersensitivity reactions
3. Autoimmune diseases
4. Immunologic deficiency syndromes
5. Amyloidosis
2. CD4+ T-cells influence the function of all of the following immune system cells,
EXCEPT:
1. B lymphocytes
2. Natural killer cells
3. Fibroblasts
4. Macrophages
5. CD8+ T-cells
3. Macrophage cytokines are characterized by all of the following, EXCEPT:
1. Mediate natural immunity
2. Regulate lymphocytes growth, activation am differentiation
3. Activate inflammatory cells
4. Inhibit hematopoesis
5. Affect leukocyte movements
4. Complement activation gives rise to all of the following proinflammatory effects,
EXCEPT:
1. Release of C3b
2. Production of chemotactic factors
3. Release of anaphylatoxins
4. Formation of antigens
5. Formation of membrane attack complex
5. Predominant cells aggregating in the form of follicles in the spleen are:
1. CD4+T-cells
2. CD8+ T-cells
3. B-lymphocytes
4. Macrophages
6. A microscopic aggregation of the epithelioid cells, usually surrounded by a collar of
lymphocytes is referred to as:
1. Papilloma
2. Condyloma
3. Melanoma
4. Lipoma
5. Granuloma
7. Cells that play an important role both in the induction and in the effector phase of im-
mune response are:
1. CD4+T-cells
2. CD8+ T-cells
3. B-lymphocytes
4. Macrophages
8. All of the following cells are involved in immune response, EXCEPT:
l. Eosinophils
2. Macrophages
4. T-lymphocytes
5. B-lymphocytes
9. Short-acting soluble mediators that induce and regulate cell interactions during immune re-
sponse are commonly called:
1. Glucagon
2. Cytokines
3. Insulin
4. Estrogen
5. Progesteron
10. The main basis for classification of hypersensitivity diseases is:
1. Immunologic
2. Biochemical
3. Non-immunologic
4. Chemical
5. Physiologic
11. The secondary mediators released during Type I hypersensitivity (anaphylactic type) are
all of the following, EXCEPT:
1. Leukotriens
2. Cytokines
3. Biogenic amines
5. Prostaglandin D2
12. All of the following diseases result from Type III hypersensitivity (immune complex
disorders), EXCEPT:
1. Glomerulonephritis
2. Farmer's lung
4. Hemolitic anemia
5. Systemic lupus erythematosus
13. Cells that compose the granuloma in type IV hypersensitivity reactions are all of the
following, EXCEPT:
1. Lymphocytes
2. Erythrocytes
3. Macrophages
5. Giant cells
14. The classical example of delayed type hypersensitivity:
1. Arthus reaction
2. Local anaphylaxis
3. Complement-dependent reaction
4. Tuberculin reaction
5. Systemic anaphylaxis
15. Morphologically, delayed-type hypersensitivity is characterized by all of the follow-
ing, EXCEPT:
1. Accumulation of the mononuclear cells around venules
2. Dermal edema
3. Deposition of fibrin in the interstitium of derma
4. Accumulation of the mononuclear cells around small vein
5. Deposition of hemosiderin in the derma
16. Systemic lupus erythematosus is associated with appearance and persistence of which
of the following agents:
1. Alloantibody
2. Alloantigens
3. Autoantigens
4. Heteroantibody
5. Heteroantigens
17. Antinuclear antibodies in systemic lupus erythematosus are directed against all of the
following, EXCEPT:
1. DNA
2. Histones
3. Nuclear membrane
4. Nonhiston proteins bound to RNA
5. Nucleolar antigens
18. The organs most commonly and seriously damaged in systemic lupus erythematosus
are all of the following, EXCEPT:
1. Skin
2. Eye
3. Joints
4. Serosal surfaces
5. Heart and vessels
19. Morphologic changes in salivary glands in Sjogren's syndrome include all of the fol-
lowing, EXCEPT:
1. Lymphocytic infiltrate
2. Atrophy of parenchyma
3. Fibrosis
4. Leukocytic infiltrate
5. Fatty replacement of parenchyma
20. Populations at high risk of human immunodeficiency virus (HIV) infection include all
of the following, EXCEPT:
1. Donors of blood and blood components
2. Homosexual and bisexual men
3. Intravenous drug users
4. Hemophiliacs
5. Infants born to HIV-infected mothers
ANSWERS
1 1 11 3
2 3 12 3
3 4 13 2
4 4 14 4
5 3 15 5
6 5 16 3
7 4 17 3
8 1 18 2
9 2 19 4
10 1 20 1
Class 10
Theme: COMPENSATORY-ADAPTIVE PROCESSES

1. Regeneration: definition, morphogenesis. Types of regeneration. Regeneration
of some tissues and organs (blood, vessels, connective and bone tissue).
2. Pathological regeneration. Metaplasia: definition, causes, typical localization,
outcomes. Displasia: definition, causes, types, outcomes.
3. Hypertrophy and hyperplasia: definitions, classifications, the reasons and
mechanisms of development.
4. Atrophy: classification, causes, morphology.
5. Reorganization of tissues and organs.
6. Organization: mechanism of development, morphological characteristic.
7. The morphology of wound healing.
Adaptation is a general biological concept integrating all the processes of vital
activity, providing the interaction of organism with the environment. Compensation
is a kind of adaptation that occurs in pathological conditions (disease) and aimed at
restoration (correction) of the disturbed function; therefore compensation is not spe-
cific but individual concept.
In medicine the adaptation and compensation are complementary processes,
that is why they are called compensatory-adaptive processes. Compensatory-adaptive
processes occur on molecular, ultrastructural, cellular, tissue, organ, system and or-
ganismal levels. Their course has several stages: initial, compensation and decom-
pensation.
HEALING AND ADAPTATION

Injury to tissue may result in cell death and tissue destruction. Healing on the
other hand, is the body response to injury in an attempt to restore normal structure
and function. The process of healing involves 2 distinct processes:
1. Regeneration when healing takes place by proliferation of parenchymal cells
and usually results in complete restoration of the original tissues.
2. Repair when healing takes place by proliferation of connective tissue ele-
ments resulting in fibrosis and scarring.
Some parenchymal cells are short-lived while others have a longer lifespan. In
order to maintain proper structure of tissues, these cells are under constant regulatory
control of their cell cycle. These include growth factors, e.g. brain, epidermis-, mac-
rophage-, nerve-, and platelet, derived growth factors.
Depending upon their capacity to divide, the cells of the body can be divided
into 3 groups: labile cells, stable cells and permanent cells.
1. Labile cells. These cells continue to multiply throughout life under normal
physiologic conditions. These include surface epithelial cells of epidermis, alimentary
tract, respiratory tract, urinary tract, vagina, cervix, uterine endometrium, hemopoiet-
ic cells of bone marrow and cells of lymph nodes and spleen.
2. Stable cells. These cells decrease or lose their ability to proliferate after ado-
lescence but retain the capacity to multiply in response to stimuli throughout adult
life. These include parenchymal cells of kidneys, liver, adrenal glands; mesenchymal
cells of smooth muscles.
3. Permanent cells. These cells lose their ability to proliferate around the time
of birth. These include: neurons of nervous system, skeletal muscle and cardiac mus-
cle cells.
Regeneration of any type of parenchymal cells involves the following 2 pro-
cesses.
1. Proliferation of original cells from the margin of the injury with migration so
as to cover the gap.
2. Proliferation of migrated cells with subsequent differentiation and matura-
tion so as to reconstitute the original tissue.
There are 3 types of regeneration: physiological, reparative and pathological.
Physiological regeneration is observed during the human life.
There are 2 types of reparative regeneration: restitution and substitution. In res-
titution, reconstruction of the original tissue in the definite organ is observed. In sub-
stitution (so called repair) connective tissue or fat appear instead of original tissue
(e.g. sclerosis develops in the area of the myocardial infarction).
The pathological regeneration may be one of the following types: hyperregen-
eration, hyporegeneration and metaplasia.
Wound Healing
Healing of skin wounds provides a classical example of combination of regen-
eration and repair described above. This can be accomplished in one of the following
two ways: healing by first intention (primary union) and healing by second intention
(secondary union).
Healing by first intention (primary union). This i s defined as healing of a
wound which has the following characteristics: clean and uninfected, surgically in-
cised, without much loss of cells and tissue, edges of wound are approximated by
surgical sutures.
The sequence of events in primary union is described below.
Immediately after injury, the space between the approximated surfaces of in-
cised wounds is filled with blood which then clots and seals the wound against hydra-
tion and infection.
Acute inflammatory response occurs within 24 hours by appearance of poly-
morphs from the margins of incision. By the 3rd day, polymorphs are replaced by
macrophages.
The basal cells of epidermis from both the cut margins start proliferating and
migrating towards incisional space in the form of epithelial spurs. A well-
approximated wound is covered by a layer of epithelium in 48 hours. The migrated
epidermal cells separate the underlying viable dermis from the overlying necrotic ma-
terial and clot, forming scab which is cast off. The basal cells from the margins con-
tinue to divide. By 5th day, a multilayered new epidermis is formed which is differ-
entiated into superficial and deeper layers.
By the 3rd day, fibroblasts also invade the wound area. By the 5th day, new
collagen fibrils start forming which dominate till healing is completed. In 4 weeks,
the scar tissue with scanty cellular and vascular elements, a few inflammatory cells
and epithelialised surface is formed.
Each suture track is a separate wound and incites the same phenomena as in
healing of the primary wound, i.e. filling the space with hemorrhage, some inflamma-
tory cell reaction, epithelial cell proliferation along the suture track from both mar-
gins, fibroblastic proliferation and formation of young collagen. When sutures are
removed around the 7th day, much of epithelialised suture track is avulsed and the
remaining epithelial tissue in the track is absorbed. However, sometimes the suture
track gets infected or the epithelial cells may persist in the track.
A sutured wound, thus takes a little longer to heal but the scar formed is neat
due to close apposition of the margins of wounds. The use of adhesive tapes avoids
this complication.
Healing by second intention (secondary union). This is defined as healing of a
wound having the following characteristics: open with a large tissue defect, at times
infected; having extensive loss of cells and tissues; the wound is not approximated by
surgical sutures but is left open.
The basic events in secondary union are similar to primary union but differ in
having a larger tissue defect which has to be bridged. Hence healing takes place from
the base upwards as well as from the margins inwards. The healing by second inten-
tion is slow and results in a large, at times ugly, scar as compared to rapid healing and
neat scar of primary union.
The sequence of events in secondary union is as follows.
As a result of injury, the wound space is filled with blood and fibrin clot which
dries.
There is an initial acute inflammatory response followed by appearance of
macrophages which clear off the debris as in primary union.
As in primary healing, the epidermal cells from both the margins of wound
proliferate and migrate into the wound in the form of epithelial spurs till they meet
the middle and re-epithelialise the gap completely, however, the proliferating epithe-
lial cells do not cover the surface fully until granulation tissue from base has started
filling the wound space. In this way, preexisting viable connective tissue is separated
from necrotic material and clot on the surface, forming scab which is cast off. In
time, the regenerated epidermis becomes stratified and keratinized.
The main bulk of secondary healing is by granulations. Granulation tissue is
formed by proliferation of fibroblasts and neovascularisation from the adjoining via-
ble elements. The newly-formed granulation tissue is deep red, granular and very
fragile. With time, the scar on maturation becomes pale and white due to increase in
collagen and decrease in vascularity. The specialized structures of skin like hair folli-
cles and sweat glands are not replaced unless their viable residues remain which may
regenerate.
Contraction of wound is an important feature of secondary healing, not seen in
primary healing. Due to the action of myofibroblasts present in granulation tissue, the
wound contracts to one-third to one-fourth of its original size. Wound contraction
occurs at a time when active granulation tissue is being formed.
Bacterial contamination of an open wound delays the process of healing due to
release of bacterial toxins that provoke necrosis, suppuration and thrombosis. Surgi-
cal removal of dead and necrosed tissue, debridement, helps in preventing the bacte-
rial infection of open wounds.
During the course of healing, the following complications may occur: infection
of wound due to entry of bacteria delays the healing; implantation (epidermal) cyst
formation may occur due to persistence of epithelial cells in the wound after healing;
pigmentation, when healed wounds may at times have rust-like colour due to staining
with hemosiderin; deficient scar formation may occur due to inadequate formation of
granulation tissue; incisional hernia a weak scar, especially after a laparotomy, hy-
pertrophied scars and keloid formation; excessive contraction; rarely scar may be the
site for development of carcinoma later, e.g. squamous cell carcinoma in scar.
Two types of factors influence the wound healing: those acting locally and
those acting in general. Local factors: infection; poor blood supply to wound, foreign
bodies including sutures interfere with healing and use intense inflammatory reaction
and infection; exposure to ionizing radiation; exposure to ultraviolet light; type, size
and location of injury. Systemic factors: age, nutrition, systemic infection, uncon-
trolled diabetes, hematological abnormalities.
HEALING IN SPECIALIZED TISSUES
Fracture healing
Healing of fracture by callus formation depends on some clinical considera-
tions whether the fracture is traumatic (in previously normal bone), or pathological
(in previously diseased bone); complete incomplete like green stick fracture; simple
(closed), comminuted (splintering of bone) or compound (communicating to skin sur-
face).
Primary union of fractures occurs occasionally in a few special situations when
the ends of fracture are approximated like by application of compression clamps. In
these cases, bony union takes place with formation of medullary callus without peri-
osteal callus formation.
Secondary union is the more common process of fracture healing. Though it is
a continuous process, secondary bone union is described under the following 3 head-
ings:
1. Procallus formation. The following steps are involved in the formation of
procallus.
Hematoma forms due to bleeding from torn blood vessels, filling the area sur-
rounding the fracture. Loose meshwork is formed by blood and fibrin clot which acts
as framework for subsequent granulation tissue formation.
Local inflammatory response occurs at the site of injury with exudation of fi-
brin, polymorphs and macrophages. The macrophages clear away the fibrin, red
blood cells, inflammatory exudate and debris. Fragments of necrosed bone are scav-
enged by macrophages and osteoclasts.
Ingrowth of granulation tissue begins with neovascularisation and proliferation
of mesenchymal cells from periosteum and endosteum. A soft tissue callus is thus
formed which joins the ends of fractured bone without much strength.
Callus composed of woven bone and cartilage starts within the first few days.
The cells of inner layer of the periosteum have osteogenic potential and lay down the
collagen as well as osteoid matrix in the granulation tissue. The osteoid undergoes
calcification and is called woven bone callus. A much wider zone over the cortex on
either side of fractured ends is covered by the woven bone callus and united to bridge
the gap between the ends, giving spindle-shaped or fusiform appearance to the union.
2. Osseous callus formation. The procallus acts as scaffolding on which osse-
ous callus composed of lamellar bone is formed. The woven bone is cleared away by
incoming osteoclasts and the calcified cartilage disintegrates. In their place, newly-
formed blood vessels and osteoblasts invade, laying down osteoid which is calcified
and lamellar bone is formed by developing Haversian system concentrically around
the blood vessels.
3. Remodeling. During the formation of lamellar bone, osteoblastic laying and
osteoclastic removal take place, remodeling the united bone ends, which after some-
time, is indistinguishable from normal bone. The external callus is cleared away,
compact bone (cortex) is formed in place of intermediate callus and the bone marrow
cavity develops in internal callus.
These are following complications of fracture healing: fibrous union, non-
union, delayed union.
Healing of Nervous Tissue
Central nervous system. The nerve cells of brain, spinal cord and ganglia once
destroyed are not replaced. Axons of CNS also do not show any significant regenera-
tion. The damaged neuroglial cells, however, may show proliferation of astrocytes
called gliosis.
Peripheral nervous system. In contrast to the cells of CNS, the peripheral
nerves show regeneration, mainly from proliferation of Schwann cells and fibrils
from distal end. Briefly, it consists of the following:
myelin sheath and axon of the intact distal nerve undergo Wallerian degen-
eration up to the next node of Ranvier towards the proximal end;
the degenerated debris are cleared away by macrophages;
regeneration in the form of sprouting of fibrils takes place from the viable end
of axon. These fibrils grow along the track of degenerated nerves so that in about 6-7
weeks, the peripheral stump consists of tube filled with elongated Schwann cells;
one of the fibrils from the proximal stump enters the old neural tube and de-
velops into new functional axon.
Healing of Muscle
All three types of muscle fibers have limited capacity to regenerate.
Skeletal muscles. The regeneration of striated muscle is similar to peripheral
nerves. On injury, the cut ends of muscle fibers retract but are held together by stro-
mal connective tissue. The injured site is filled with fibrinous material, polymorphs
and macrophages. After clearance of damaged fibres by macrophages, one of the fol-
lowing two types of regeneration of muscle fibres can occur. If the muscle sheath is
intact, sarcolemmal tubes containing histiocytes appear along the endomysial tube
which, in about 3 months time, restores properly oriented muscle fibres e.g. in
Zenker's degeneration of muscle in typhoid fever. If the muscle sheath is damaged, it
forms a disorganized multinucleate mass and scar composed of fibrovascular tissue,
e.g. in Volkman's ischaemic contracture.
Smooth muscles. Non-striated muscle has limited regenerative capacity, e.g.
appearance of smooth muscle in the arterioles in granulation tissue. However, in large
destructive lesions, the smooth muscle is replaced by permanent scar tissue.
Healing of Mucosal Surfaces
The cells of mucosa have very good regeneration and are normally being lost
and replaced continuously, e.g. mucosa of alimentary tract, respiratory tract, urinary
tract, uterine endometrium, etc. This occurs by proliferation from margins, migration,
multilayering and differentiation of epithelial cells in the same way as in the epider-
mal cells in healing of skin wounds.
Healing of Solid Epithelial Organs
Following gross tissue damage to organs like kidney, liver and thyroid, the re-
placement is by fibrous scar, e.g. in chronic pyelonephritis and cirrhosis of liver.
However, in parenchymal cell damage with intact basement membrane or intact sup-
porting stromal tissue, regeneration may occur. For example, in tubular necrosis of
kidney with intact basement membrane, proliferation and slow migration of tubular
epithelial cells may occur to form renal tubules; in viral hepatitis if part of the liver
lobule is damaged with intact stromal network, proliferation of hepatocytes may re-
sult in restoration of liver lobule.
ATROPHY
Atrophy means reduction of the number and size of cells, tissues and organs in
living organism characterized by decrease or stopping of their function.
Atrophy may be physiologic and pathologic.
A. Physiologic atrophy. It is a normal process of aging in some tissues:
1. Atrophy of lymphoid tissue in lymph nodes, appendix and thymus.
2. Atrophy of gonads after menopause.
3. Atrophy of brain.
4. Atrophy of bones.
It may be obliteration of the umbilical arteries and arterial duct (Botallow's) af-
ter birth.
B. Pathologic atrophy maybe general and local.
General atrophy is observed in cachexia due to:
Oncologic and chronic diseases.
Starvation.
Injury of hypophysis (endocrine cachexia).
Injury of hypothalamus (cerebral cachexia).
Gross appearance of patients is seen as:
Severe exhaustion.
Adipose tissue is decreased and it has brown color.
Muscles are atrophied; skin is dry and flabby.
Internal organs are small, brown color and often shrunken.
Osteoporosis takes place.
Histologically:
Cells become smaller in size but are not dead cells.
Shrinkage in cell size is due to reduction in cell organelles.
Accumulation of lipofuscin around nucleus takes place (lipofuscin wear
and tear pigment is a golden yellow pigment representing undigested lipid material
derived from cellular metabolism see class 3).
Local atrophy has several types:
1. Ischemic atrophy develops due to insufficiency of the blood supply. Hy-
poxia stimulates the proliferation of fibroblasts and forms sclerosis. For example:
small atrophic kidney in atherosclerosis of renal artery, atrophy of brain in cerebral
atherosclerosis.
2. Disuse atrophy (dysfunctional) develops due to reduction of the function of
organ: atrophy of muscles due to immobility, atrophy of the pancreas in obstruction
of pancreatic duct.
3. Neuropathic atrophy due to interrupted nerve supply: poliomyelitis, motor
neuron disease, nerve section, and inflammation of facial nerve.
4. Endocrine atrophy: hypopituitarism may lead to atrophy of thyroid, adrenal
and gonads; hypothyroidism may cause atrophy of the skin and its adnexal structures.
5. Pressure atrophy: compression of spine by tumor in nerve root, compres-
sion of skull by meningioma arising from pia-arachnoid mater, compression of ster-
num by aneurysm of aorta arch, compression of renal tissue by dilated renal pelvic in
hydronephrosis, compression of brain tissue by dilated ventricles in hydrocephalus.
6. Atrophy due to chemical and physical influences. For example: action of
the radiation lead to atrophy of bone marrow and genital organs.
7. Idiopathic atrophy: myopathies, testicular atrophy.
The atrophic tissue may be replaced by fatty ingrowths. Atrophy is reversible
provided the cause is eliminated or deficiencies restored.
HYPERTROPHY AND HYPERPLASIA
Hypertrophy refers to an increase in the size of parenchyma resulting in en-
largement of the organ or tissue, without any change in the number of cells.
Hyperplasia is an increase in the number of parenchymal cells resulting in en-
largement of the organ or tissue. Quite often, both hyperplasia and hypertrophy occur
together.
Mechanisms of hypertrophy:
hypertrophy of tissue arises due to increase of size of functional cells. Thus,
the hypertrophied organ has no new cells, just larger cells.
hypertrophy of tissue arises due to increase of number of functional cells (hy-
perplasia of cells).
hypertrophy of cells arises due to both increase of size of functional cells and
increase of number of ultrastructural elements. Thus, the increased size of the cells is
due not to an increased intake of fluid, called cellular swelling, or edema, but to the
synthesis of more structural components. It is called true hypertrophy.
False hypertrophy is the increase of the size of organs due to growth of con-
nective tissue, accumulation of the fluid or fatty tissue. It results in atrophy of organ
(hydronephrosis, hydrocephalus, obesity of heart).
True hypertrophy (hyperplasia) has adaptive and compensative characteristics
and may be physiologic and pathologic:
A. Physiologic hypertrophy (hyperplasia).
1. Neurohumoral (hormonal) hypertrophy: hypertrophy of female breast at pu-
berty, during pregnancy and lactation, hypertrophy of pregnant uterus, proliferative
activity of normal endometrium after a normal menstrual cycle, prostatic hyperplasia
in old age.
2. Working hypertrophy of skeletal muscle: hypertrophied muscles in athletes
and manual labour.
B. Pathologic hypertrophy (hyperplasia).
1. Neurohumoral hypertrophy develops due to impairment of endocrine
functions. Endometrial glandular hyperplasia following estrogen excess production
which results in metrorrhagia; atrophy of testis leads to increase of breast (gyneco-
mastia); hyperfunction of anterior hypophysis lobe (adenoma) leads to an increase in
skeleton size (acromegaly).
2. Working hypertrophy develops in tissues consisting of stable undivided
cells due to increase of their size. It may be often in cardiac muscle at some cardiac
diseases, such as: systemic hypertension, aortic valve disease (stenosis and in-
sufficiency), mitral insufficiency; hypertrophy of smooth muscle: cardiac achalasia
(in esophagus), pyloric stenosis (in stomach), and intestinal stricture; hypertrophy of
urine bladder in adenoma of prostatic glands.
3. Compensatory reparative hyperplasia: regeneration of the liver following
partial hepatectomy, regeneration of epidermis after skin abrasion; bone marrow after
blood loss.
4. Vicarious (substitutional) hypertrophy: following nephrectomy on one
side in a young patient there is compensatory hypertrophy as well as hyperplasia of
the nephrons of the other kidney.
5. Hypertrophic vegetations develop due to chronic inflammation in mucous
membranes (polyps and condylomas); lymphostasis leads to ingrowth of connective
tissue, examples of false hypertrophy. In wound healing, there is formation of granu-
lation tissue.
According to stage of adaptation two types of myocardial hypertrophy have
been described:
Concentric. In concentric hypertrophy (clinically, no insufficiency) the mus-
culature is clearly enlarged, measuring till 1.8 cm, but chambers of the heart are not
dilated.
Eccentric. In eccentric hypertrophy, myocardium is enlarged but chambers of
the heart are dilated. This leads to hemodynamic disorder with cardiac insufficiency.
It is called myogenic dilatation.
The affected organ is enlarged and firm. For example: a hypertrophied heart of
a patient with systemic hypertension may weight 700-800 g as compared to average
normal adult weight of 350 g. There is the enlargement of muscle fibers as well as of
nuclei. At ultrastructural level, there is increased synthesis.
Metaplasia.
Tissues may adapt to environment stimuli by a change in cell differentiation termed
metaplasia. Metaplasia (meta = transformation, plasia = growth) is defined as a re-
versible change of one type of epithelial or mesenchymal mature cells to another type
of mature epithelial or mesenchymal cells (strictly limited by one germinal layer);
usually in response to action of abnormal stimulus, and often reverts back to normal
after the elimination of stimulus. However, if the stimulus persists for a long time,
epithelial metaplasia may transform into cancer.
Certain long-standing environmental stimuli render the environment unsuitable
for some specialized cell types and, as an adaptive response, the proliferating cells
change their pattern of differentiation. These cells can adapt to a change in environ-
ment by differentiating to a new, mature, stable type of cell, which better equips them
to withstand environmental stress. This process is termed metaplasia.
Metaplasia occurs in many tissue types. In the bronchi, under the influence of
chronic irritation by cigarette smoke, the normal ciliated columnar mucus-secreting
respiratory epithelium is replaced by squamous epithelium (squamous metaplasia). In
the cervix, the normal columnar epithelium of the lower endocervix changes to
squamous epithelium in response to exposure to the acid vaginal environment (squa-
mous metaplasia). In the urinary bladder, the normal transitional epithelium may be
replaced by squamous epithelium in response to chronic irritation by bladder stones
or infection (squamous metaplasia). The esophageal squamous epithelium is replaced
by columnar epithelium in response to exposure to gastric acid in cases of gastric re-
flux.
Metaplasia most commonly occurs in epithelial tissues, but may also be seen
elsewhere. For example, areas of fibrous tissue exposed to chronic trauma may form
bone (osseous metaplasia). In many settings, metaplasia co-exists with hyperplasia;
e.g., the squamous epithelium that arises by metaplasia in response to stone in the
bladder may also be hyperplastic.
Adaptive responses in disease occur only with tolerable environmental chang-
es. The adaptive responses of hyperplasia, hypertrophy, atrophy, involution and met-
aplasia occur only if the damaging stimulus is tolerable to the affected cells. Failure
to adapt leads to cell damage and, if the stimulus is severe or prolonged, may result in
cell death. Adaptive responses allow cells to survive in the face of a change in the
cellular environment. Failure to adapt is associated with cell damage or cell death.
DYSPLASIA
Dysplasia means disordered cellular development, often accompanied with
metaplasia and hyperplasia, it is therefore also referred to as atypical hyperplasia.
Epithelial dysplasia is characterized by cellular proliferation and cytological changes,
which include:
Hyperplasia of epithelial layers.
Irregular arrangement of cells from basal layer to the surface layer.
Cellular and nuclear pleomorphism.
Increased nucleocytoplasmic ratios.
Nuclear hyperchromatism.
Increased mitotic activity.
ORGANIZATION
Organization is the replacement of pathological changed foci by mature con-
nective tissue that leads to sclerosis. Sclerosis is a pathological process that leads to a
diffusive or focal induration of internal organs, connective tissue, blood vessels due
to excessive growth of mature connective tissue.
Classification.
I According to etiology and pathogenesis.
1 Sclerosis is the outcome of chronic proliferative inflammation (at infectious,
infectious-allergic, immune diseases, encapsulation of foreign substances).
2 Sclerosis is the outcome of connective tissue disorganization (at rheumatic
diseases).
3 The substitutive sclerosis. It is the outcome of necrosis and atrophy.
4 Scars as the result of wounds and ulcers healing.
5 Organization of blood clots, hematomas, formation of adhesions.
II. According to morphogenesis three mechanisms are revealed.
1 Neoformation of young connective tissue due to proliferation of fibroblasts
(at productive inflammation, necrosis).
2 Reinforced collagen syntheses by fibroblasts without significant hyperplasia
of cells;
3. Transformation of loose connective tissue into fibrous tissue (at chronic ve-
nous congestion).
4. Class work.

139 Hypertrophy of the heart Pay attention to the heart size, ventricle
wall thickness, size of cavities. Which chambers of the heart show more changes?
83 Scar in the place of kidney infarction. Specimen is an example of
substitution. There is a large whitish scar in the kidney parenchyma. This scar is con-
nective tissue growth in the place of dead tissue.
110 Hydronephrosis Pay attention to the kidney size, pelvis and calyx
condition, kidney parenchyma thickness. Name the atrophy kind.
322 Hyperplasia of prostate gland Pay attention to the prostate gland
size and thickness of urinary bladder wall. Name and describe the pathological pro-
cesses in the prostate gland and the urinary bladder.

50- Normal myocardium (hematoxylin and eosin staining). (Figure A),
50 Hypertrophy of myocardium (Figure B). Microscopically, diagnose hyper-
trophy of myocardium by comparing of hypertrophic myocardium with normal cardi-
ac muscle. Note the size of cardiomyocytes and stroma. Study the appearance of
cardiomyocytes and their nuclei. Draw.
A B
51 Glandular hyperplasia of uterus mucous coat. (hematoxylin and eo-
sin staining). Pay attention to the endometrium thickness, amount of glands in it.
Note peculiarities, number of cellular elements in the glands and stroma. Draw.
Increased number of
Increased number cells in epithelium of
of cells in stroma glands
8 Brown atrophy of liver (hematoxylin and eosin staining). Pay attention

to the hepatocytes size, their nuclei and accumulation of pigment near hepatocytes
nucleus. Name the pigment. Draw.
Pigment ac-
cumulation
6 Hydronephrosis (hematoxylin and eosin staining). Note the kidney
parenchymal thinning, atrophy of most of the glomeruli and their replacement by
connective tissue, atrophy of tubules (dilation of lumen, flattening of epithelium).
Name the kind of atrophy?
Atrophy of tubular
epithelium
107 Myocardiosclerosis. (hematoxylin and eosin staining). Pay attention

to the cardiomyocytes size, size of muscular cells around scar, their nuclei size and
shape. Name the kind of regeneration in the myocardium. Draw.
Connective tissue
Myocardial filres

Regeneration of some tissues and organs
Tissue and Type of Mechanism
organ regeneration
Heart Mainly intracellular There is a connective tissue growth in the place of myo-
(substitution con- cardial fibers damage. Hypertrophy of adjacent myocar-
nective tissue dial fibers due to hyperplasia of their ultrastructures de-
growth) velops.
Liver
Brain
Epithelium
Vessels
Atrophy
Type Causes of development Characteristics, fate
Disuse atrophy (dysfunc- It develops due to reduction of The rate of metabolism and blood
tional) the function of organ: atrophy of supply are decreased in the organ
muscles due to immobility, atro- or tissue, the organ and its cells are
phy of the pancreas in obstruc- decreased in size. Fate: reversible
tion of pancreatic duct in case of physical exercises and
Neuropathic atrophy massage
Ischemic atrophy
Endocrine atrophy
Pressure atrophy
Atrophy due to chemical
and physical influences
Idiopathic atrophy
Types of organization
Types Mechanisms of development Characteristics
1. Wounds heal- 1 Neoformation of young connective tis- 1. Sclerosis is the outcome of
ing sue due to proliferation of fibroblasts (at chronic productive inflammation
2. Organization productive inflammation, necrosis). (at infectious, infectious-allergic,
of blood clots, 2 Reinforced collagen syntheses by fi- immune diseases, encapsulation of
hematomas, ne- broblasts without significant hyperplasia foreign substances).
crotic foci of cells; 2 Sclerosis is the outcome of con-
3. Incapsulation 3. Transformation of loose connective nective tissue disorganization (at
tissue into fibrous tissue (at chronic ve- rheumatic diseases).
nous congestion). 3 The substitutive sclerosis. It is
the outcome of necrosis and atro-
phy.
4 Scars as the result of wounds and
ulcers healing.
5 Organization of blood clots, he-
matomas, formation of adhesions.
Hypertrophy
Hypertrophy kind Causes Morphogenesis
Working hypertrophy Increased workload on or- Hypertrophy of cells (increase in
gan the tissues of which their ultrastuctures number)
consisting of stable undivid-
ed cells
Neurohumoral
Vicarious
Hypertrophic vegetations
4. Clinical tasks.
1. A patient who suffered from chronic glomerulonephritis for a long period of time
had hypertensive vascular disease. The patient died from acute cardiac insufficiency.
1. What macroscopic changes of the heart can be revealed at autopsy?
2. What microscopic changes can be found in the myocardium?
3. What is the variant of compensatory-adaptive process?
4. What is the stage of this compensatory-adaptive process?
2. A patient had a resection of 1/3 of the liver after trauma.
1. What changes can be seen subsequently in the area of resection and residual
part of the liver?
2. What is the name of the process in liver?
3. A patient who suffered from stomach cancer with multiple metastases died of ex-
haustion.
1. What microscopic changes can be found in the heart at autopsy?
2. What is the name of this process?
3. In what other organs and tissues does the same process occur?
4. What is the reason for brown color of these organs?
4. A patient underwent resection of the lung lobe due to bronchiectases which com-
plicated the chronic bronchitis. On histological examination of the lung, chronic in-
flammation and presence of stratified squamous epithelium instead of columnar cili-
ated epithelium in the bronchial wall were revealed.
1. What is the name of the pathological change of bronchial epithelium?
2. What factors encourage the development of the process?
3. What disease can develop as a complication of this process?
5. A diagnostic biopsy of the vaginal part of the cervix was performed on a 28-year-
old woman. On histological examination of the taken specimen, chronic inflamma-
tion and presence of columnar epithelium instead of squamous stratified epithelium
were found.
1. What is the name of the pathological change of the epithelium in the vaginal
part of the cervix?
2. What factors encourage the development of the process?
3. What disease can develop as a complication of this process?
ANSWERS
Number of question with answer
1 1 2 3 4
Hypertrophy of the left Hypertrophy of Working hypertrophy Stage of decompen-
ventricular wall of the myocardial fi- sation
myocardium bers
2 Proliferation of hepato- Reparative hy-
cytes pertrophy of
liver
3 Atrophy of myocardial Brown atrophy Liver, skeletal mus- Deposition of lipid-
fibers of the heart cles, neurons ogenous pigment -
lipofuscin
4 Metaplasia Chronic inflam- Metaplasia is a
mation premalignant condi-
tion, thus squamous
cancer can develop as
the complication of
metaplasia
5 Metaplasia Chronic inflam- Metaplasia is a
mation premalignant condi-
tion, thus squamous
cell cancer can devel-
op as the complication
of metaplasia
5. Self assessment.
1. The cellular adaptation without cell proliferation includes all of the following, EXCEPT:
1. Apoptosis
2. Atrophy
3. Hyperplasia
4. Hypertrophy
5. Metaplasia
2. Hypertrophy is characterized by:
1. Pathologic hypertrophy of the breast during lactation
2. Hypertrophy of the skeletal muscle cells in a body-builder
3. Pathologic hypertrophy of the uterus during pregnancy
4. Hypertrophy of the skeletal muscle cells in a patient with immobilized broken limb
5. Hypertrophy of the endometrium due to ovarian tumor
3. The causes of hypertrophy are all of the following, EXCEPT:
1. Mechanical triggers
2. Trophic triggers
3. Nervous triggers
4. Polypeptide growth factors
5. Vasoactive agents
4. Pressure-overloaded (concentric) cardiac hypertrophy is characterized by all of the fol-
lowing, EXCEPT:
1. Hypertrophy of left ventricle
2. Increased wall thickness
3. Normal left cavity diameter
4. Dilated left cavity diameter
5. Reduced left cavity diameter
5. The hypertrophic and dilated (eccentric) heart is characterized by all of the following,
EXCEPT:
1. Decreased mass and diminished left wall thickness
2. Increased mass and normal left wall thickness
3. Normal mass and left wall thickness
4. Normal mass and diminished left wall thickness
5. Increased mass and diminished left wall thickness
6. Hyperplasia is characterized by:
1. Increase in the size of cells
2. Increase in the number of cells
3. Increase in the number of nuclei in cells
4. Shrinkage in the size of cells
5. Atypia of cells
7. The proliferation of the glandular epithelium of a female during pregnancy is an exam-
ple of:
1. Compensatory hyperplasia
2. Pathologic hyperplasia
3. Hormonal hyperplasia
4. Compensatory hypertrophy
5. Hormonal hypertrophy
8. The hyperplasia of hepatic cells that occurs after partial hepatoectomy is an example of:
1. Pathologic hyperplasia
2. Hormonal hyperplasia
3. Hormonal hypertrophy
4. Compensatory hyperplasia
5. Compensatory hypertrophy
9. Simple endometrial hyperplasia is characterized by all of the following, EXCEPT:
1. Increase in the number and size of endometrial glands
2. Atypia of gland cells
3. Complex endometrial glands
4. Increase in gland-to-stroma ratio
5. Dilated endometrial glands
10. Hypoplasia is characterized by all of the following, EXCEPT:
1. Incomplete development of an organ
2. Decreased number of cells
3. Increased number of cells
4. Underdevelopment of an organ
5. Decreased function of an organ
11. One of the variants of physiologic atrophy is:
1. Atrophy of skeletal muscle by the immobilized broken limb
2. Atrophy of uterus after parturition
3. Kidney atrophy from pressure (hydronephrosis)
4. Atrophy of the endometrium by ovarian tumor
5. Atrophy of the brain in atherosclerosis
12. Causes of pathologic atrophy are all of the following, EXCEPT:
1. Loss of endocrine stimulation
2. Loss of innervation
3. Diminished blood supply
4. Decreased workload
5. Increased workload
13. Hydronephrosis is characterized by all of the following, EXCEPT:
1. Thickening of the renal parenchyma
2. Thinning of the renal parenchyma
3. Dilatation of the renal pelvis
4. Dilatation of the renal calyces
5. Progressive atrophy of the kidney
14. The causes of pathologic atrophy are all of the following, EXCEPT:
1. Aging
2. Intracellular fat accumulation
3. Pressure
4. Inadequate nutrition
5. Denervation
15. In atrophy, the cells are:
1. Dead cells
2. Increased in size
3. Irreversibly injured cells
4. Reversibly injured cells
5. Shrunken cells
16. What pigment can be found in the cytoplasm of the heart and muscle cells in aging at-
rophy?
1. Lipofuscin
2. Melanin
3. Hemosiderin
4. Bilirubin
5. Ferritin
17. For metaplasia which of the following holds true:
1. It is a disordered growth
2. It affects only epithelial tissues
3. It affects only mesenchymal tissues
4. It is an irreversible and progressive change
5. It is a reversible change
18. The replacement of the normal secretory columnar epithelium by the nonfunctioning
stratified squamous epithelium may occur in all of the following organs, EXCEPT:
1. Bile ducts of the liver
2. Excretory ducts of the salivary glands
3. Excretory ducts of the pancreas
4. Respiratory epithelium of the bronchi
5. Tubular epithelium of the kidney
19. Dysplasia is characterized by all of the following, EXCEPT:
1. Abnormal organization of cells
2. Loss in the uniformity of individual cells
3. Loss in cell architectural organization
4. Replacement of one adult cell type by another adult cell type
5. Variation of cells in size and shape
20. Which pathologic process results from dysplasia?
1. Aplasia
2. Hypoplasia
3. Hyperpigmentation
4. Calcification
5. Neoplasia
ANSWERS
1 3 11 2
2 2 12 5
3 3 13 1
4 4 14 2
5 5 15 5
6 2 16 1
7 3 17 5
8 4 18 5
9 2 19 4
10 3 20 5
Class 11
Theme: TUMORS. GENERAL CHARACTERISTICS. MESENCHYMAL
TUMORS.
I. Study the questions:

1. Etiology of tumors (causal oncogenesis).
2. Structure and characteristics of tumor cells.
3. Morphological atypical features of tumor.
4. Tumor growth.
5. Tumor histogenesis.
6. Tumor progression.
7. Benign mesenchymal tumors.
1. Fibroma, its variants.
2. Lipoma, its variants.
3. Leiomyoma. Rabdomyoma. Granular cellular tumor.
4. Hemangioma, its variants. Lymphangioma.
5. steoma. Benign osteoblastoma.
6. Chondroma. Benign chondroblastoma.
8. Malignant mesenchymal tumors.
1. Fibrosarcoma, its variants.
2. Liposarcoma, its variants.
3. Leiomyosarcoma, rabdomyosarcoma, malignant granular cellular tumor.
4. Angiosarcoma, its variants.
5. Malignant synovioma, mesothelioma.
6. steosarcoma.
7. Chondrosarcoma.
Tumor (neoplasm, blastoma) is a pathological process that is characterized by

abnormal, excessive, uncoordinated, autonomous and purposeless proliferation of
cells.
Tumors are classified according to histogenesis with the account of their mor-
phological structure, localization, peculiarity of their structure in a definite organ, be-
nign or malignant anticipated behavior.
The classification was suggested as an international one by the Committee on
Tumor Nomenclature of the International Anticancer Union. According to this classi-
fication, there are 7 groups of tumors, their total number exceeds 200.
1. Epithelial tumors without specific localization (organ-nonspecific).
2. Tumors of endocrine and exocrine glands as well as epithelial integuments (organ
specific).
3. Mesenchymal tumors.
4. Tumors of melanin-forming tissue.
5. Tumors of nervous system and brain coats.
6. Tumors of blood.
7. Teratomas.
According to their behavior and clinicomorphological characteristics tumors
are divided into 3 groups: 1) benign, 2) malignant, 3) tumors with local destructive
growth.
Benign tumors (mature) consist of differentiated mature cells. They are charac-
terized by 1) tissue atypia, which is a property that distinguishes tumor cells and tis-
sues from their normal organotypic and histotypic structure (abnormality of paren-
chyma and stroma ratio, abnormality of size and shape of tumor structures, irregular
arrangement of structures); 2) slow expansive growth; 3) the tumor does not usually
cause a systemic effect to the organism; 4) the tumor does not produce metastases; 5)
the relapse is rare. Benign tumors may become malignant.
Malignant (immature) tumors consist of not completely differentiated cells.
These tumors produce metastases. Metastasis is a detachment of the tumor cells from
the site of the origin and their spread to other organs.
Metastases can be:
1) lymphogenic (they are carried through the lymphatic vessels to regional lymphatic
nodes);
2) hematogenous (they are carried with the blood flow to distant organs);
3) implantation (contact), when a tumor disseminates through the serous layers (peri-
toneum, pleura) and grow to the adjacent organs.
Malignant tumors often relapse. Relapse is appearance of the tumor in the
place where it was removed.
Malignant tumors produce both local and general effects on the organism. A
local effect manifests with squeezing and destruction of the surrounding tissues. Gen-
eral effect on the organism is characteristic for all malignant tumors, it manifests with
metabolic disturbances and cachexia development.
Malignant tumors are characterized by tissue, cellular (a property that distin-
guishes tumor cells from normal cells: pleomorphism of cells, increased N-C ratio,
loss of polarity, hyperchromatism and pleomorphism of nuclei, increased number of
mitoses, abnormal mitoses), biochemical, histochemical and antigenic atypia as well
as atypia of ultrastructures.
There are different types of tumor growth: expansive, appositional, and infil-
trative (invasive).
The expansive growth means the tumor growth out of itself moving away and
squeezing the surrounding tissues. This type of growth is slow, and is characteristic
for benign tumors.
Appositional growth occurs due to transformation of normal cells into tumor
ones.
In infiltrative (invasive) growth the cells of the tumor invade normal tissues
and destroy them (so called destructive growth).
In relation to the lumen of the tube organ, the growth of the tumor may be en-
dophytic or exophytic. Endophytic growth is infiltrative growth of the tumor deep
into the wall of the organ. Exophytic growth is expansive growth of the tumor to the
cavity (lumen) of the organ.
According to the number of foci of primary tumor development, tumor can be
unicentric (one focus) and multicentric (several foci).
The tumors with local destructive growth take the intermediate place between
benign and malignant. They have the features of infiltrating growth but do not give
metastases.
Structure of tumor. The gross appearance of the tumor is various. Its shape
may resemble a node, a mushroom cap or cauliflower, a saucer. Its surface may be
smooth, bumpy, and papillary. The tumor may grow as a node with distinct borders
(well-circumscribed), it may have a capsule. The size of the tumor can be different.
Its consistence depends on prevalence of parenchyma or stroma in it. It may be either
soft or solid (dense).
Secondary changes in the tumor result from disturbances of blood circulation
in it as well as from chemo- or radiotherapy. They manifest by foci of necrosis, hem-
orrhages, inflammation, formation of mucus, calcification.
Etiology of tumors is various: 4 theories are recognized.

1. Viral carcinogenesis theory. It states the integration of the virus and the normal
host cell genomes, i.e. a combination of nucleic acid of the virus with genetic appa-
ratus of the cell which turns into tumor cell. Oncogenic viruses are: Epstein-Barr vi-
rus, herpes virus, hepatitis B virus, human papillomavirus, etc.
2. Physicochemical theory suggests that tumor appears under the influence of differ-
ent physical and chemical substances, so called carcinogens.
3. Dysontogenetic theory was created by J. Cohnheim. According to his theory, tu-
mors appear from embryonic tissue heterotopias (displacement) and abnormally de-
veloped tissues under the influence of different provoking agents.
4. Polyetiological theory emphasizes the importance of different factors, i.e. chemi-
cal, physical, viral, parasite, and dyshormonal.
MESENCHYMAL TUMORS
In ontogenesis, mesenchyma is the origin of: 1) connective tissue, 2) vessels, 3)
adipose tissue, 4) smooth and striated muscles, 5) serous coats, 6) hemopoietic sys-
tem, 7) bones, 8) cartilage.
Mesenchymal tumors develop from: 1) connective (fibrous) tissue, 2) fat tissue,
3) muscular tissue, 4) blood and lymphatic vessels, 5) synovial tissue, 6) mesothelial
tissue, 7) bone and cartilage.
They may be benign (name of the tissue + oma) and malignant (name of the tis-
sue + sarcoma). There are also special terms (e.g. desmoid, granular-cell tumor).
Connective (fibrous) tissue tumors

Most frequent benign connective (fibrous) tissue tumors are:
1. Fibroma a node of differentiated connective tissue with different direction
of the cellular bands:
a) dense: fibrous component prevails over the cellular elements;
b) soft: loose connective tissue with great amount of stroma cells (fibroblasts
and fibrocytes).
Localization of fibroma is varied: skin, breast, spinal canal, orbit, etc. Fibroma
of the skin may have a pedicle.
2. Desmoid fibroma is a kind of dense fibroma that is characterized by infiltrative
growth and relapses. More often it is located in the anterior abdominal wall.
3. Dermatofibroma (histiocytoma) is a small fibrous node with yellow-brown colour.
More often it is located in the skin of the limbs. It consists of capillaries and connec-
tive tissue with fibrous structures and fibroblasts, fibrocytes, histiocytes, macrophag-
es. There are giant multinuclear cells containing lipids and hemosiderin among cells.
Fibroblasts are arranged in a cart-wheel or storiform pattern.
Malignant connective (fibrous) tissue tumors are characterized by atypical
cells.
Macroscopically sarcoma looks like fish flesh. As a rule sarcoma metastases
disseminate by haematogenous route.
1. Fibrosarcoma looks like a node or an irregular formation. There are 3 types
of fibrosarcoma:
a) differentiated fibrosarcoma, termed cellular-fibrous fibrosarcoma, when fibrous
component prevails over the cellular component;
b) poorly differentiated fibrosarcoma, termed cellular sarcoma. It produces metastases
more frequently;
c) round cell tumors of unknown origin, termed unclassified tumor.
2. Malignant fibrous hystiocytoma consists of numerous polymorphic fibro-
blast-like and histiocyte-like cells, multinucleate bizarre giant cells, and numerous
mitotic figures. There is a tendency for the spindle shape cells to be arranged in a
characteristic cart-wheel or storiform pattern. It grows slowly though its growth is
infiltrating. Metastases are frequent.
Tumors of adipose tissue

Benign
1. Lipoma: a soft node, sometimes in a capsule, yellow, composed of lob-
ules of mature adipose cells of different size separated by delicate fibrous septa. It
may develop in every site of adipose tissue location.
Intramuscular infiltrating lipoma is an infrequent benign tumor without distinct
borders, it infiltrates the striated muscle.
2. Hibernoma is a rare tumor of brown fat. It consists of large round cells
with granular or foamy cytoplasm (fat vacuoles).
Malignant
1. Liposarcoma is a rare, large tumor, which is composed mostly of lipoblasts
and small amount of lipocytes of different degree of maturity.
There are several types of liposarcoma:
a) well-differentiated liposarcoma;
b) myxoid (embryonic);
c) round cell liposarcoma;
d) pleomorphic liposarcoma.
It grows slowly. The prognosis of liposarcoma depends upon the location and
histologic type. For instance, round cell and pleomorphic liposarcomas metastasize
frequently.
2. Malignant hibernoma is a very rare tumor with cellular polymorphism and
lots of giant cells.
Tumors of muscles
Benign
1. Leiomyoma consists of smooth muscle with chaotic location of the muscular tissue
bands, the stroma has vessels and nerves. If stroma prevails this tumor is termed fi-
bromyoma. Secondary changes are necrosis, hemorrhages, cysts, hyalinosis, petrifac-
tion.
2. Rhabdomyoma consists of striated muscles. It resembles embryonic muscular fi-
bres and myoblasts. Cardiac rhabdomyoma appears as a hamartomatous lesion and is
accompanied by other developmental defects (large masses of striated muscles). Soft
tissue rhabdomyomas are predominantly located in the head and neck, tongue, etc.
and composed of large, round to oval cells, having abundant, granular cytoplasm.
3. Granular-cell tumor (Abrikosow's tumor): this is a small tumor in a capsule. Usual-
ly it is located in the tongue, esophagus, and skin. The cells are large, round or po-
lygonal, uniform, with granular cytoplasm (no lipids).
Malignant
1. Leiomyosarcoma (malignant leiomyoma) is a tumor with cellular and tissue atypia
and large number of mitoses (high mitotic index).
2. Rhabdomyosarcoma (malignant rhabdomyoma) is characterized by considerable
pleomorphism, loss of muscular tissue characteristic (it is necessary to use special
immune antibodies to verify the histogenesis of tumor).
3. Malignant granular-cell tumor (malignant myoblastoma) resembles malignant
rhabdomyoma but the cytoplasm is granular.
Tumors of blood and lymph vessels

Benign tumors of blood vessels
1. Hemangioma is a tumor of blood vessels. There are several types of he-
mangioma:
a) capillary, which develops in the skin, mucous membranes, gastrointestinal tract,
liver, more often in children. It looks like cyanotic node comprised of branching
blood-filled capillaries with narrow lumen, and thin walls;
b) venous: vascular bands with smooth muscles, resembling veins;
c) cavernous hemangioma is common in the liver, skin, bones, muscles, gastrointes-
tinal tract, brain, composed of thin-walled cavernous vascular spaces, filled partly or
completely with blood. The vascular spaces are lined by flattened endothelial cells.
They are separated by scanty connective tissue stroma;
d) benign hemangiopericytoma arises in the skin and intramuscular space of the ex-
tremities. The tumor is composed of capillaries surrounded by pericytes outside the
vascular basement membrane.
2. Glomus tumor (glomangioma). More often develops in hand and feet
(fingers and toes). It consists of vessels surrounded by ferrules of epithelioid (glo-
mus) cells. Tumor is rich in nerves thus it is usually painful in touch.
Malignant tumors of blood vessels.
Angiosarcoma:
a) malignant hemangioendothelioma;
b) malignant hemangiopericytoma is a highly malignant tumor. Its cells
have high mitotic rate and areas of necrosis. Tumor is characterized by early metasta-
ses.
Benign tumors from lymph vessels.
Lymphangioma: characterized by growth of lymphatic vessels in different di-
rections with the formation of a node or enlargement of the organ. If lymphangioma
develops in the tongue, it is termed macroglossia. If lymphangioma develops in the
lip it is termed macrocheilia. Microscopically it looks like cavities filled with lymph.
Malignant tumors from lymph vessels. Lymphangiosarcoma. It appears as a re-
sult of chronic lymphatic stasis and is composed of lymph clefts with proliferating
atypical endothelial cells.
Tumors of synovial tissue

1. Benign synovioma develops in the tendons and tendon sheath. It con-
tains a lot of stroma with hyalinosis, and a little number of vessels. It may have xan-
thome cells and clefts.
2. Synovial sarcoma (malignant synovioma) develops in the large joints. It has
irregular structure. Some tumors have pleomorphic cells and pseudoepithelial gland
formations with cysts, the others have fibroblast-like atypical cells and collagen fi-
bers, structures resembling tendons.
Tumors of mesothelial tissue

1. Benign mesothelioma resembles a dense node in serous membrane (pleura),
its structure is similar to fibroma (fibroid mesothelioma).
2. Malignant mesothelioma (peritoneum, pleura, and pericardium) microscopi-
cally looks like atypical large cells with vacuolated cytoplasm. Malignant mesotheli-
oma may have tubular and papillary structures. In this case it is called epithelial mes-
othelioma.
Bone tumors
Benign
1. Osteoma develops as a rule in spongy and tubular bones, skull. 2 types
of osteoma are known: a) spongy osteoma, b) compact osteoma.
This benign tumor almost exclusively involves the skull and facial bones; the
frontal sinus is the most common location. Males are affected more often than fe-
males, the lesion can occur at any age. Although osteoma is predominantly a solitary
lesion, multiple osteomas can occur in association with intestinal polyposis and soft
tissue tumors. The tumor of normal dense and mature bone originates from the peri-
osteum. There is little evidence of osteoblastic activity.
2. Osteoid osteoma is common in young persons, mostly males. Macro-
scopically, an osteoid osteoma appears as a small round or oval mass containing a
central red-brown, friable area. Microscopically, the tumor appears as a maze of ir-
regular bone trabeculae, fibrous tissue, and vessels. The center of the tumor is rich in
osteoblasts, calcification, and multinucleate giant cells.
3. Benign osteoblastoma predominantly affects the vertebrae and long bones of
young males in the first three decades of life. Macroscopically, the lesions vary in
size from a few to several centimeters. Microscopically, osteoblasts proliferate and
osteoid production increases. Osteoclasts and multinucleate giant cells may be very
numerous, especially in areas of blood extravasation.
Malignant
1. Osteosarcoma (osteogenic sarcoma) from osteogenic tissue rich in atypical
cells of osteoblastic type with a lot of mitoses, the bone is primitive. 2 types of osteo-
sarcoma are known: a) osteoblastic type (bone formation), b) osteolytic type (bone
destruction).
Osteosarcoma is a highly malignant bone tumor characterized by the produc-
tion of osteoid and bone. Most osteosarcomas arise in the metaphyseal end of long
bones (predominantly the femur, humerus, and tibia), but they can involve any bone,
including the small bones of the hands, feet and face. Osteosarcoma is the most
common primary malignant tumor of a bone (next to multiple myeloma), accounting
for approximately 16% of all bone malignancies. The disease predominantly affects
young males between age 10 and 20.
Gross appearance. The tumor appears as a large necrotic and hemorrhagic
mass. The lesion usually ends in the epiphyseal cartilage and rarely extends into the
nearby joint space.
Microscopic appearance. Three types of osteosarcomas have been differentiat-
ed according to their predominant histologic patterns: osteoblastic, fibroblastic and
chondroblastic. The hallmark of the tumor is the presence of a malignant stroma that
contains osteoid and bone. The stroma shows bizarre pleomorphic cells, with hyper-
chromatic, irregular nuclei and abundant mitoses. Multinucleate giant cells are seen
most often near zones of necrosis and calcification. Malignant cartilage may be pre-
sent in small foci or as a large proportion of the tumor.
2. Giant cell tumor of bone (osteoclastoma) is an uncommon malignant tumor
characterized by multinucleate giant cells. It occurs predominantly in women over
age 19 and peaks in the third decade of life. The lesion almost always is localized in
the distal portion of the long bones (femur or humerus), and 50% of these tumors oc-
cur in the area of the knee. Occasionally, the tumor involves the skull, pelvis, or small
bones of the hands and feet.
Macroscopically, the tumor characteristically appears as multiple hemorrhagic
cystic cavities that destroy the adjacent bone and are enclosed by a thin shell of new
bone formation.
Microscopically, a vascularized stroma composed of spindle cells which con-
tain multinucleate giant cells. Tumor cells are intermixed with areas of hemorrhage,
inflammation, and hemosiderin deposits. Mitoses are present.
Cartilage tumors
Benign
1. Chondroma derives from hyaline cartilage in the feet, spine, breastbone,
and pelvis. If tumor is located in the peripheral area of the bone it is termed exchon-
droma, if in the central area of the bone enchondroma.
Ollier's disease (enchondromatosis) is a rare, nonhereditary disorder in which
multiple chondromas are present in the metaphysis and diaphysis of various bones.
Maffucci's syndrome is a congenital disease characterized by dyschondroplasia
and multiple hemangiomas in the skin and viscera.
This neoplasm is thought to originate from heterotropic cartilaginous cell; nests
in the medullary cavities of bones. Macroscopically, the lesion appears as a confluent
mass of bluish hyaline cartilage with a lobular configuration. Microscopically, the
cartilage appears moderately cellular, with occasional binucleate cells. Mitoses are
absent.
2. Osteochondroma is the most common benign tumor of bone affecting
patients under age 21. The lesions may be single or multiple and predominantly in-
volve the metaphysis of long bones. Macroscopically, the tumor may range in size
from 1 to several centimeters and appears as a stalked protuberance, with a lobulated
surface jutting from the affected bone. The periosteum of the adjacent bone covers
the lesion. Microscopically, the cartilaginous cells appear lined up, mimicking the
orientation of cartilaginous cells in a normal epiphysis. No mitoses are present.
3. Benign chondroblastoma consists of chondroblasts, interstitial substance, marked
osteoclast reaction. Chondroblastoma is a rare cartilaginous tumor that almost always
involves the epiphyseal portion of the long bones. The tumor predominantly affects
males in the second decade of life. Macroscopically, the tumor is round or oval in
shape, with areas of cystic degeneration and hemorrhage. Microscopically, prolifera-
tion of chondroblasts is intermixed with varying amounts of fibrous stroma and
chondroid material. Multinucleate giant cells and calcifications are present. Mitoses
are virtually absent.
4. Chondromyxoid fibroma is most commonly located in the metaphysis of long
bones but occasionally can involve the epiphysis. It primarily affects males in the
first and second decades of life. Macroscopically, the tumor is a well-circumscribed,
solid mass with a cartilaginous appearance. The cortex of the bone is expanded by the
tumor, which is limited by the periosteum. Microscopically, a variety of fibrous,
myxomatous, and chondroid elements are seen together with multinucleate giant cells
and macrophages that contain hemosiderin. When the tumor forms lobules, a conden-
sation of nuclei occurs beneath the rim of the compressed adjacent tissue.
Malignant
Chondrosarcoma is a malignant cartilaginous tumor. The most common loca-
tions are the spine, pelvic bones, and upper ends of the femur and humerus. The tu-
mor may arise de novo (primary chondrosarcoma) or originate from a preexisting be-
nign cartilaginous lesion (secondary chondrosarcoma). Chondrosarcomas comprise
between 7% and 15% of all bone neoplasms. The tumor occurs in patients between
age 30 and 60 and in men three times more often than in women.
Macroscopically, a chondrosarcoma appears as a lobulated white or gray mass
that contains mucoid material and foci of calcification.
Microscopically, there are islands of immature or poorly developed cartilage in
which anaplastic cells with two or more nuclei are present within the lacunar space.
The neoplasm is slow growing and can remain locally aggressive for years,
with a high tendency to recur and implant in soft tissues. Hematogenous dissemina-
tion to the lungs, liver, and kidneys takes place over the years, with eventual death of
the patient. The 10-year survival rate ranges from 50% to .60%.
3. Class work.

333 Fibroma The tumor is surrounded by a capsule, the cut surface of
the tumor is white.
305 Leiomyoma Find whitish-grey node in the myometrium with
cords.
336 Lipoma The tumor is surrounded by a capsule, the cut surface of
the tumor is yellowish and tallowy.
330 Chondrosarcoma The tumor resembles cartilaginous tissue, it has
no capsule, invades into surrounding tissues.
329 Osteosarcoma The tumor has dense consistency, grayish color,
invades into surrounding tissues.
223 Sarcoma metastasis to the lung There are multiple dense grayish
foci in the lung.
19 Cancer metastasis into the myocardium (hematoxylin and eosin

staining). Find tumor cell complexes among myocardial fibers (arrow).
100 Mixed tumor. (hematoxylin and eosin staining). Study the slide using
low magnification. Find bundles and foci of epithelial cells (a), cartilage (b) and con-
nective tissue (c), foci of calcification.
a b
c
93 Leiomyoma. (hematoxylin and eosin staining). Pay attention to the lo-
calization, character, direction of muscular fibers and their bundles. Note the features
of tumor growth. Draw.
82 Cavernous angioma of liver. (hematoxylin and eosin staining). Study

the slide using low magnification. Note the tissue atypia, irregular localization of ves-
sels, thickness of vascular wall, size and shape of lumen, interrelation with surround-
ing tissue.
86 Rhabdomyosarcoma. (hematoxylin and eosin staining). Note the fea-
tures of tissue and cellular atypia, find mitotic figures and atypical mitoses (a), sec-
ondary changes (hemorrhages b). Draw.
b
a
III. Complete the tables (see theoretical part)
Clinicomorphological features of tumors

Anticipated behavior of Clinical features Gross features Microscopic features
tumor
Benign tumors Slow growth, usually
have asymptomatic
course (except tu-
mors of the central
nervous system),
Malignant tumors
Histogenetic classification of tumors

Tissue Benign Malignant
Name Variants Name Variants
Adipose tissue Lipoma Fibrolipoma Liposarcoma Well-differentiated liposarcoma;
Hibernoma Malignant myxoid (embryonic);
hibernoma round cell liposarcoma;
pleomorphic liposarcoma
4. Clinical tasks.
1. A 45-year-old man noticed that a round shape mass in the adipose tissue of his
forearm which had been slowly increasing since one year got the size 2 cm in diame-
ter. The mass was surgically removed. Grossly, the tumor is yellowish, tallowy, and
has a capsule. Microscopically, it is composed of cells which resemble lipocytes and
have the property of been stained with Sudan III.
1. What tumor developed in the patient?
2. What is the histogenesis of this tumor?
3. Which property of the tumor causes it to be stained with Sudan III?
2. A 58-year-old woman had a hysterectomy because of uterus tumor. Grossly, it
was a grayish poorly-circumscribed node in the myometrium which resembled fish
flesh.
Microscopically, the tumor was composed of pleomorphic cells with hyperchromic
nuclei, numerous mitoses (including atypical mitoses); cells of the tumor resembled
myocytes of myometrium. On X-ray examination, multiple foci from 0.5 to 3 cm in
diameter were revealed in the lungs.
1. What tumor was revealed in the uterus of the patient?
2. What types of morphological atypia are present in this tumor?
3. What is the name of the foci which were found in the patients lungs?
3. On ultrasonic examination, a round shape mass 3 cm in diameter surrounded by

capsule was revealed in the liver of a 45-year-old woman. The mass was surgically
removed. On histological examination, the mass consisted of multiple cavernous ves-
sels filled with blood.
1. What is the name of the revealed tumor?
2. What diseases should be included in differential diagnosis of this tumor?
3. What other histological variants of blood vessel tumor do you know?
4. A poorly-circumscribed tumor of a muscle of the left thigh was found in a 56-

year-old man. Microscopically, the tumor was composed of pleomorphic cells with
hyperchromic nuclei, multiple mitoses, including atypical one. Tumor cells resem-
bled myocytes of skeletal muscle. On X-ray examination multiple metastases were
revealed in the lungs.
1. What tumor was diagnosed in the patient?
2. What is the histogenesis of the tumor?
3. What is the route of tumor metastasis to lungs?
5. A 35-year-old man had a round shape firm movable mass 1 cm in diameter in a

skin of the left shin for 3 years. The tumor was surgically removed. On histological
examination, it was diagnosed that the tumor was formed of chaotically situated col-
lagen fibers and fibroblasts. The tumor was surrounded by capsule. The Van Giesons
staining revealed red color of the tumor components.
1. What is the name of this tumor?
2. What is the histogenesis of the tumor?
3. What type of morphological atypia is characteristic for this tumor?
ANSWERS
1 2 3
1 Benign tumor lipoma Adipose tissue Tumor cells contain lipids
2 Leiomyosarcoma Cellular and tissue atypia Metastases
3 Cavernous hemangioma Parasitic diseases (Echinococ- Capillary, venous angioma,
cus); tumors of other histogen- glomangioma, benign he-
esis; abscess mangiopericytoma
4 Rhabdomyosarcoma Striated muscle Hematogenous spread
5 Benign tumor fibroma Connective tissue Tissue atypia
5. Self assessment.
1. The nomenclature of tumors is based on:
1. Stromal component
2. Localization
3. Inflammatory changes
4. Vascular component
5. Parenchymal component histogenesis
2. Dysplasia is characterized by all of the following, EXCEPT:
1. Loss of cell uniformity
2. Hyperchromatic enlarged nuclei
3. Appearance of mitotic figures
4. Loss of cell architectural orientation
5. Formation of tumor giant cells
3. Hamartoma refers to:
1. Tumor differentiating towards more than one cell line
2. Tumor arising from totipotent cells
3. Mass of disorganised but mature cells indigenous to the particular site
4. Mass of ectopic rests of normal tissue
5. Extravasation of blood into the tissues with resultant swelling
4. Increased number of normal mitoses may be present in the following tissues, except:
1. Bone marrow cells
2. Nails
3. Endometrial reticular cells
4. Hepatocytes
5. Intestinal epithelium
5. Carcinogenic influence of radiation appears after:
1. 112 months
2. 12 years
3. 25 years
4. 510 years
5. > 10 years
6. The important factors associated with the increasing incidence of tumors are all of the
following, EXCEPT:
1. Age
2. Diet
3. Environment
4. Acute inflammation
5. Genetic makeup
7. The following hereditary diseases have higher incidence of cancers due to inherited de-
fect in DNA repair mechanism, except:
1. Ataxia telangiectasia
2. Xeroderma pigmentosum
3. Adenomatous polyposis coli
4. Bloom's syndrome
5. Hereditary non-polyposis colorectal cancer
8. Women receiving estrogen therapy have an increased risk of developing the following
cancers, except:
1. Breast cancer
2. Endometrial carcinoma
3. Gallbladder cancer
4. Hepatocellular carcinoma
5. Cervical cancer
9. Anaplasia is characterized by all of the following, EXCEPT:
1. Cellular and nuclear pleomorphism
2. Formation of tumor giant cells
3. Formation of atypical mitotic figures
4. Formation of Langhans' giant cells
5. Hyperchromatic nuclei
10. The growth of neoplasms is critically dependent on which of the following?
1. Localization
2. Tumor stroma
3. Neutrophils immigration
4. Lymphatic drainage
5. Inflammatory reaction
11. The extracellular matrix components that contribute to the tumor cell invasion into
the basement membranes are all of the following, EXCEPT:
1. E-cadherin
2. Laminin
3. CD8
4. Fibronectin
5. Type IV collagen
12. The criteria for differentiating between benign and malignant tumors are all of the
following, EXCEPT:
1. Maturity
2. Rate and character of growth
3. Localization
4. Anaplasia
5. Metastases
13. Malignant tumor is characterized by all of the following, EXCEPT:
1. Increased abnormal tissue mass
2. Uncoordinated invasive growth
3. Relatively autonomous growth
4. Decreased abnormal tissue mass
5. Metastases
14. Negative effects resulting from neoplasia are all of the following, EXCEPT:
1. Compression of adjacent tissues
2. Cachexia
3. Destruction of adjacent tissues
4. Paraneoplastic syndrome
5. Cancer obesity
15. Cells that are believed to participate in the destruction of tumor cells include all of the
following, EXCEPT:
1. Activated macrophages
2. Stem cells
3. CD4 -cells
4. T-killer cells
5. CD8-cells
16. A tumor is called medullary when it is almost entirely composed of:
1. Amyloid stroma
2. Large areas of necrosis
3. Abundant lymphoid tissue
4. Parenchymal cells
5. Stromal cells
17. Malignant tumors arising from mesenchymal tissue are referred to as:
1. Sarcomas
2. Adenocarcinomas
3. Papillomas
4. Cystadenomas
5. Polyps
18. The term for a benign mesenchymal tumor is constructed by combining the word des-
ignating the tumor cell origin with the addition of:
1. -sarcoma
2. -carcinoma
3. -oma
4. -itis
5. -osis (-asis)
19. Benign tumor arising from osteoblasts is called:
1. Chondroma
2. Adenoma
3. Osteoma
4. Fibroma
5. Papilloma
20. Benign tumors from lipid and muscular tissues include the following, EXCEPT:
1. Lipoma
2. Leiomyoma
3. Liposarcoma
4. Rhabdomyoma
5. Hybernoma
ANSWERS
1 5 11 3
2 5 12 3
3 3 13 4
4 2 14 5
5 2 15 2
6 4 16 4
7 3 17 1
8 3 18 3
9 4 19 3
10 2 20 3
Class 12
Theme: TUMORS OF EPITHELIAL, NERVOUS, AND MELANIN-
PRODUCING TISSUES.

1. Organ non-specific epithelial tumors.
2. Organ specific epithelial tumors:
a) Exocrine glands (liver, kidney, breast, uterus).
b) Skin.
c) Tumors of endocrine glands (sex glands, thyroid gland, adrenal gland,
thymus, APUD- system, etc.).
3. Tumors of melanin-producing tissue.
4. Tumors of nervous tissue.
Organ non-specific epithelial tumors develop in squamous, transitional or

glandular epithelia which do not perform any specific function.
Benign organ non-specific epithelial tumors are subdivided according to their
origin from different types of epithelium into the tumors of squamous and transitional
epithelium (papillomas), tumors of glandular epithelium (adenomas).
Papilloma is a tumor originating from the skin and mucous membranes, cov-
ered with squamous or transitional epithelium; it looks like a ledge or a bush of
branching papillae. It is a good example of an exophytic tumor. The base of the tumor
consists of connective tissue containing blood vessels. It is a continuation of subepi-
thelial connective tissue covered with epithelium like with a glove.
Adenoma is a benign epithelial tumor from the epithelium of the glands and
mucous membranes covered with columnar epithelium. More often they can be found
in the breast, thyroid gland, ovaries, prostate gland, uterus, and gastrointestinal tract.
Grossly, adenoma is a soft whitish or pinkish node of different size. According
to the histological structure adenoma may be tubular, trabecular, papillary and al-
veolar. In tubular adenoma, there are glandular cavities resembling tubes in the con-
nective tissue with vessels. In alveolar adenoma, numerous foci bedded with cylindri-
cal or cubic epithelium are observed in the connective tissue with vessels. Trabecular
adenoma consists of cellular cords, while papillary type of adenoma is composed of
papillary structures. Sometimes papillary growth of epithelium, bedding glandular
cavities, is observed. In some adenomas glandular cavities are widened and form
large cavities, cysts filled with serous fluid or mucus. These cyst-like adenomas are
called cystadenomas. In all these cases, the epithelium is separated from the sur-
rounding tissue by its own membrane. Adenomas may transform into malignant tu-
mors.
Immature or malignant tumor of epithelium is called cancer. The popularity of
this term can be explained by the increase of the cancer incidence in the 20th century
comparing with previous centuries.
Histologically, there are the following types of differentiated carcinoma:
1. Carcinoma in situ is a variant of cancer which is characterized by
severe atypia, active cellular proliferation while infiltrative growth is ab-
sent, and basement membrane is not destroyed. Noninvasive cancer is a step
of cancer growth and it can transform into infiltrative malignant tumor. This
tumor is well studied in many organs: cervix, mammary gland, skin, stom-
ach, larynx, etc.
2. Squamous cell carcinoma may arise on any part of the skin or
mucous membranes lined by squamous epithelium (oral cavity, esophagus,
larynx, vagina, uterus cervix, etc.). It can arise on glandular or transitional
epithelium after preceding metaplasia. Grossly, this carcinoma is more
commonly an ulcerated poorly-circumscribed growth with elevated and in-
durated margin, less often, fungating or polypoid verrucous with necrotic
and ulcerative lesions. Microscopically, squamous carcinoma is character-
ized by irregular downward proliferation of epithelial cells in derma or un-
derlying tissues with the formation of epithelial nests. Masses of tumor cells
show atypical features such as variation in cell size and shape, nuclear hy-
perchromatism, absence of intercellular bridges, atypical mitoses, individual
cell keratinisation or whorled arrangement of malignant squamous cells
forming horn pearls.
3. Transitional cell carcinoma.
4. Adenocarcinoma arises on prismatic epithelium of mucous mem-
branes or epithelium of glands. It has a structure similar to adenoma but dif-
fers from it in presence of atypia, variation in cell and nucleus size and
shape, nuclear hyperchromatism, atypical mitoses and infiltrative growth.
There are the following variants of adenocarcinoma: acinar, tubular and pa-
pillary.
Types of undifferentiated carcinoma.
1. Mucous (colloid) carcinoma. The tumor grows like masses having gelati-
nous appearance due to secretion of large quantities of mucus. Histologically, mucoid
carcinoma contains abundant pools of mucin in which are seen a small number of
tumor cells.
2. Signet-ring cell carcinoma is a variant of mucous carcinoma when the mu-
cous accumulates in cytoplasm of tumor cells. Signet-ring tumor cells have abundant
mucinous cytoplasm positive for mucicarmine.
3. Small cell carcinoma. Tumor cells are small, uniform, and lymphocyte-like
with scanty cytoplasm. This carcinoma has rapid growth, frequently undergoes ne-
crosis, gives early and multiple metastasis.
4. Fibrous (scirrhous) carcinoma. If there is excessive connective tissue stroma
in the undifferentiated carcinoma, it is referred to as desmoplasia and the tumor is
hard or scirrhous. Due to marked desmoplasia cancer cells may be difficult to find.
5. Medullary carcinoma. If undifferentiated carcinoma is almost entirely com-
posed of parenchymal cells, it is called medullary. The loose connective tissue stroma
is scanty and usually has a prominent lymphoid infiltrate.
6. Solid carcinoma is characterized by presence of solid sheets and ribbons of
malignant epithelial cells separated by connective tissue which show marked cytolog-
ic atypia and multiple mitoses.
ORGAN SPECIFIC EPITHELIAL TUMORS.

TUMORS OF EXOCRINE GLANDS AND SKIN.
Hepatic tumors.
Metastatic tumors are much more common than primary tumours in the liver.
Primary hepatic tumours may arise from hepatic cells and bile duct epithelium.
Benign hepatic epithelial tumours include hepatocellular (liver cell) adenoma
and bile duct adenoma (cholangioma).
Hepatocellular adenoma usually occurs singly but about 10% are multiple. It is
partly or completely encapsulated and slightly lighter in colour than adjacent liver
tissue or may be bile-stained. Histologically, the tumor is composed of sheets and
cords of hepatocytes. Hepatocellular adenomas lack portal tracts and bile ducts but
bile canaliculi containing bile-plugs may be present.
Intrahepatic or extrahepatic bile duct adenoma is a rare benign tumour. The
tumour may be small, composed of acini lined by biliary epithelium and separated by
variable amount of connective tissue, or are larger cystadenomas having locules lined
by biliary epithelium.
Malignant hepatic tumours are hepatocellular carcinoma and cholangiocarci-
noma, and frequently mixed pattern is seen.
Hepatocellular carcinoma (hepatoma) may form a single yellow-brown, large
mass, with central necrosis, haemorrhage and occasional bile-staining (expanding or
massive type). Less often, multifocal, multiple masses 3-5 cm in diameter, scattered
throughout the liver are seen (multifocal or nodular type). Rarely, the hepatocellular
carcinoma forms diffusely infiltrating tumour mass ranging from well-differentiated
to highly anaplastic lesions.
Cholangiocarcinoma is the designation used for carcinoma arising from bile
duct epithelium within the liver and from the large hilar ducts. Grossly, the tumour is
firm to hard and whitish. Microscopically, the tumour has glandular structure. The
tumour cells resemble biliary epithelium or diffuse type. Microscopically, the tumour
cells resemble hepatocytes but vary with the degree of atypia and have no bile secre-
tion.
Tumors of kidney.
Both benign and malignant tumours occur in the kidney. They may arise from
renal tubules (adenoma, adenocarcinoma) and embryonic tissue (nephroblastoma or
Wilms tumor).
Adenoma of kidney. Histologically, there are basophilic, clear cell and aci-
dophilic types of adenoma. Clear cell adenoma may form tiny nodules up to 3 cm in
diameter. It is encapsulated and white or yellow. Microscopically, it is composed of
tubular cords or papillary structures projecting into cystic space. The cells are usually
uniform, cuboidal with no mitosis. However, size of the tumor rather than histologic
criteria is considered more significant parameter to predict the behavior of the tumor
those larger than 3 cm in diameter are potentially malignant. Other types of adeno-
ma are mahogany-brown or tan and have variable size.
Renal cell carcinoma (synonyms: adenocarcinoma of kidney, hypernephroma,
Grawitz tumour) is classified into clear cell, papillary, granular cell, chromophobe,
sarcomatoid and collecting duct type. Grossly, renal cell carcinoma is a solitary and
unilateral, generally large, golden yellow and circumscribed tumor. Papillary tumours
may be multifocal. Cut section of the tumor commonly shows large areas of ischaem-
ic necrosis, cystic change and foci of haemorrhages. Another significant characteris-
tic is the frequent presence of tumor thrombus in the renal vein which may extend
into the vena cava.
Nephroblastoma or Wilms tumor is an embryonic tumor derived from primi-
tive renal epithelial and mesenchymal components. It is the most common abdominal
malignant tumour of young children, seen most commonly between 1 to 6 years of
age with equal sex incidence. Grossly, the tumor is usually quite large, spheroidal,
replacing most of the kidney. On cut section, the tumor shows variegated appearance
soft, fish flesh like grey-white to cream-yellow tumor with foci of necrosis and
haemorrhages. Microscopically, nephroblastoma shows mixture of primitive epitheli-
al and mesenchymal elements. Most of the tumor consists of small, round to spindled
cells, abortive tubules and poorly-formed glomerular structures are present. Mesen-
chymal elements such as smooth and skeletal muscle, cartilage and bone, fat cells and
fibrous tissue, may be seen.
Breast tumors.
Among the important benign breast tumours are fibroadenoma and intraductal
papilloma. Fibroadenoma is a benign tumour of fibrous and epithelial elements.
Grossly it is a small, solitary, well-encapsulated, spherical or discoid mass. The cut
surface is firm, grey-white, slightly myxoid. Microscopically, there are intracanalicu-
lar and pericanalicular patterns. Intraductal papilloma is a benign papillary tumor oc-
curring most commonly in a lactiferous duct or lactiferous sinus near the nipple.
Carcinoma of the breast is an important malignant tumor which occurs as non-
invasive (carcinoma in situ) and invasive cancer with its various morphologic varie-
ties. Non-invasive carcinoma may be intraductal carcinoma and intralobular carcino-
ma. There are several types of invasive carcinoma. They are infiltrating ductal carci-
noma, invasive lobular carcinoma, medullary carcinoma, colloid carcinoma and other
rare morphologic forms.
Non-invasive (in situ) carcinoma. In general, noninvasive or in situ carcinoma
is characterized histologically by presence of tumour cells within the ducts or lobules
without evidence of invasion.
Infiltrating ductal carcinoma is the classic breast cancer. Macroscopically, the
tumor is irregular, 1-5 cm in diameter, hard cartilage-like mass that cuts with grating
sound. The sectioned surface of the tumour is gray-white to yellowish with chalky
streaks and often extends irregularly into the surrounding fat. Microscopically, as the
name suggests, the tumour is different from other special types in lacking a regular
and uniform pattern throughout the lesion. There are 3 histological types of this car-
cinoma:
anaplastic tumour cells forming solid nests, cords, poorly-formed glandular struc-
tures and some intraductal foci;
infiltration by these patterns of tumour cells into diffuse fibrous stroma and fat;
invasion into perivascular and perineural spaces as well as lymphatic and vascular
invasion.
Infiltrating (invasive) lobular carcinoma. Invasive cancers in being more fre-
quently bilateral; and within the same breast, it may have multicentric origin. Macro-
scopically, the appearance varies from a well-defined scirrhous mass to a poorly-
defined area of induration that may remain undetected by inspection as well as palpa-
tion. Microscopically, there are 2 characteristics: 1) Pattern a characteristic single
file (Indian file) linear arrangement of stromal infiltration by the tumour cells with
very little tendency to gland formation is seen. Infiltrating cells may be arranged con-
centrically around ducts in a target-like pattern; 2) Tumour cytology individual tu-
mour cells resemble cells of in situ lobular carcinoma. They are round and regular
with very little pleomorphism and infrequent mitoses. Some tumors may show signet-
ring cells distended with cytoplasmic mucus.
Medullary carcinoma has a significantly better prognosis than the usual infil-
trating duct carcinoma, probably due to good host immune response in the form of
lymphoid infiltrate in the tumour stroma. Macroscopically, the tumour is character-
ized by a large, well-circumscribed, rounded mass that is typically soft and fleshy
brain-like.
Colloid (mucinous) carcinoma contains large amount of extracellular epithelial
mucin and acini filled with mucin.
Paget's disease of the nipple. The nipple bears a crusted, scaly eczematoid le-
sion with a palpable subareolar mass in about half the cases. Macroscopically, the
skin of the nipple and areola are crusted, fissured and ulcerated with oozing of se-
rosanguineous fluid from the erosions. Microscopically, the skin lesion is character-
ized by the presence of Paget's cells singly or in small clusters in the epidermis. The-
se cells are larger than the epidermal cells. The underlying breast contains invasive or
non-invasive duct carcinoma which shows no obvious direct invasion of the skin of
nipple.
Skin tumors.
The skin is the largest organ of the body. Tumours and tumour-like lesions may
arise from different components of the skin such as surface epidermis, epidermal ap-
pendages and dermal tissues. Each of these tissues may give rise to benign and ma-
lignant tumours. The most important of epidermal appendages tumors
are:hidradenoma, spiradenoma, trichoepithelioma, and basal cell carcinoma.
Hidradenoma originates from the intradermal portion of the eccrine sweat duct.
Histologically, it consists of solid masses and cords of tumour cells which may have
an occasional duct-like structure containing mucin.
Spiradenoma is found as solitary, painful, circumscribed nodule in the dermis.
Histologically, it consists of lobules which are surrounded by a thin capsule. The tu-
mor lobules contain 2 types of epithelial cells like in the secretory coils of the eccrine
sweat gland.
Trichoepithelioma is a tumor of hair follicle. The tumor may occur as solitary
lesion or as multiple inherited lesions, predominantly on the face, scalp and neck. It is
often circumscribed. The most characteristic histologic feature is the presence of mul-
tiple horn cysts surrounded by basophilic cells.
Basal cell carcinoma is a locally invasive, slow-growing hair follicle tumor
that rarely metastasizes (0.05% of all cases). Grossly, the most common pattern is a
nodulo-ulcerative basal cell carcinoma in which a slow-growing small nodule under-
goes central ulceration with pearly, rolled margins. Microscopically, the most charac-
teristic feature is the proliferation of basaloid cells (resembling basal layer of epider-
mis) having typical peripheral palisaded appearance of the nuclei.
Malignant appendage tumors are very rare. There are sweat gland carcinoma
and sebaceous carcinoma.
Uterus.
Gestational trophoblastic diseases resulting from malignant overgrowth of
trophoblast invasive mole and choriocarcinoma are significant morphologic lesions
which should be discussed as organ specific tumors of uterus.
Invasive (destructive) mole (chorioadenoma destruens) shows invasion of the
molar tissue into the uterine wall which may be a source of haemorrhage. Rarely, mo-
lar tissue may invade the blood vessels and reach the lungs. Microscopically, the le-
sion is benign and identical to classic mole but has potential for haemorrhage.
Choriocarcinoma is a highly malignant and widely metastasizing tumour of
trophoblast. Features: 1) absence of stroma, 2) invasion of the blood vessels, lym-
phatics, and myometrium, 3) widespread haematogenous metastases are early and
frequent, found chiefly in the lungs. Choriocarcinoma is composed of masses and
columns of highly anaplastic and bizarre cytotrophoblast and syncytiotrophoblast
cells which are intermixed. The tumor is also characterized by invariable presence of
haemorrhages and necrosis.
TUMORS OF ENDOCRINE GLANDS.

Ovarian tumors.
Ovarian tumors arise from normally-occurring cellular components of the ova-
ry. There are five major groups:
1). Tumors of surface epithelium (serous tumors, mucinous tumors, etc.).
2). Germ cell tumours (teratomas, dysgerminoma, yolk sac tumor, etc.).
3). Sex cord-stromal tumours (granulosa cell tumour, thecoma, fibroma, etc.)
4). Miscellaneous tumors.
5). Metastatic tumors.
Benign and malignant serous tumors are large unilocular or multiloculated
cysts with intracystic papillary projections. Serous cystadenoma is characteristically
lined by properly-oriented low columnar epithelium. Serous cystadenocarcinoma has
multilayered malignant cells which show loss of polarity, presence of solid sheets of
anaplastic epithelial cells and definite evidence of stromal invasion.
Mucinous tumours are predominantly cystic tumours which contain mucin.
Grossly, mucinous tumours are much larger than serous tumors. Mucinous cystade-
noma has thin wall and septa dividing the loculi. It is lined by a single layer of co-
lumnar nonciliated epithelium lining the loculi. There is very little tendency to papil-
lary proliferation of epithelium. Mucinous cystadenocarcinoma usually has thickened
areas and is characterized by piling up of malignant epithelium, at places forming sol-
id sheets, papillary formation, adenomatous pattern and infiltration into stroma with
or without pools of mucin.
Dysgerminoma is an ovarian counterpart of seminoma of the testes. All dys-
germinomas are malignant and are extremely radiosensitive. The tumor cells are ar-
ranged in diffuse sheets, islands and cords separated by scanty fibrous stroma which
contains lymphocytic infiltrate.
Granulosa cell tumor may occur at all ages. It invades locally but occasionally
may have more aggressive and malignant behavior. Most granulosa cell tumours se-
crete oestrogen. Cut section of tumor is yellowish-brown. Microscopically, the granu-
losa cells are arranged in a variety of patterns including micro- and macrofollicular,
trabecular, bands and diffuse sheets.
Thecoma is usually benign. It occurs more frequently in postmenopausal wom-
en. Grossly, thecoma is a solid and firm mass, cut surface is yellowish. Histological-
ly, it consists of spindle-shaped theca cells of the ovary admixed with variable
amount of hyalinised collagen.
Testicular tumours.
Based on classification, all testicular tumors are divided into 3 groups: germ
cell tumours (seminoma, embryonal carcinoma, teratoma, yolk sac tumor, etc.), sex
cord-stromal tumours (Leydig cell tumor, Sertoli cell tumor, etc.) and mixed forms
(gonadoblastoma).
Seminoma is the commonest malignant tumour of the testis and corresponds to
dysgerminoma in female. The tumor has a peak incidence in the 4 th decade of life.
Grossly, the involved testis is enlarged up to 10 times its normal size. Cut section
shows homogeneous, grey-white lobulated appearance. Tumor cells generally lie in
cords, sheets or columns forming lobules.
Leydig (interstitial) cell tumors are quite uncommon. They may occur at any
age but are more frequent in the age group of 20 to 50 years. The tumor cells secrete
androgen, or both androgen and oestrogen, and rarely corticosteroids. Crossly, the
tumor appears as a small, well-demarcated and lobulated nodule. Cut surface is ho-
mogeneously yellowish or brown. The tumor is composed of sheets and cords of
normal-looking Leydig cells.
Sertoli cell tumors (androblastoma) may occur at all ages but are more fre-
quent in infants and children. The tumor may elaborate oestrogen or androgen and
may account for gynaecomastia in an adult or precocious sexual development of
child. The tumour is fairly large, firm, round, and well circumscribed. Cut surface of
the tumour is yellowish or yellow-grey.
Gonadoblastoma is an example of combination of both germ cells and sex cord
stromal components.
Thyroid tumors.
Most tumors of the thyroid are of follicular epithelial origin; few arise from
parafollicular C-cells.
The most common benign thyroid neoplasm is a follicular adenoma. It is char-
acterized by four features so as to distinguish it from a nodule of nodular goitre: 1.
solitary nodule; 2. complete encapsulation; 3. clearly distinct architecture inside and
outside the capsule; 4. and compression of the thyroid parenchyma outside the cap-
sule. There are the following 6 types of growth pattern: 1). Microfollicular adenoma;
2). Normofollicular adenoma; 3). Macrofollicular (colloid) adenoma; 4). Trabecular
adenoma; 5). Oxyphilic adenoma; 6). Atypical adenoma.
Thyroid cancer. Carcinoma of the thyroid gland has 4 major morphologic types
with distinctly different clinical behavior and variable prevalence. These are papil-
lary, follicular, medullary and undifferentiated (anaplastic) carcinoma.
Papillary carcinoma is the most common type of thyroid carcinoma. Papillae
are composed of fibrovascular stalk and covered by single layer of tumour cells
which have characteristic nuclear features (optically clear appearance).
Follicular thyroid carcinoma is composed of follicles of various sizes and may
show trabecular or solid pattern. Vascular and adjacent structures invasion are signif-
icant features.
Medullary thyroid carcinoma is derived from parafollicular or C-cells. There
are 3 distinctive features of this tumor: familial occurrence, secretion of calcitonin,
and amyloid stroma.
Anaplastic carcinoma is one of the most malignant tumors in humans. The tu-
mour is generally composed of 3 types of cells occurring in varying proportions:
small cells, spindle cells and giant cells.
Parathyroid tumours. Parathyroid adenoma and carcinoma are the neoplasms
found in parathyroid glands, the former being much more common than the latter.
Most adenomas are characterized by the excessive secretion of parathyroid hormone
causing features of hyperparathyroidism. These tumors are composed of chief cells
arranged in sheets or cords.
Tumours of adrenal glands are uncommon and include distinct adrenocortical
tumours and medullary tumors. There are 4 types of cortical adenoma: 1). clear cell
cortical adenoma (produces aldosterone and results in Conns syndrome); 2). dark
cell cortical adenoma (produces androgens and causes virilism or rarely Cushings
syndrome); 3). mixed cortical adenoma (is characterized by hypercortisolism Cush-
ings syndrome); 4). glomerulosa cell adenoma (characterized by increased secretion
of mineralocoticoids). Cortical carcinoma is characterized by cellular atypia, local
invasion as well as spread to distant sites.
Pheochromocytoma is generally a benign tumor arising from the chromaffin
cells of the adrenal medulla. The most common feature of pheochromocytoma is hy-
pertension, which results from secretion of catecholamines. About 10% of pheo-
chromocytomas may be malignant having tendency for osseous metastases.
Thymoma is a tumor of epithelial origin. It may arise from cortical and medul-
lar cells. Clinically, it is asymptomatic, but sometimes it causes myasthenia, immu-
nodeficiency and autoimmune diseases. There are 4 types of thymoma: 1. cortical cell
thymoma (characterized by invasive growth and cellular atypia); 2. medullar cell
thymoma (generally benign); 3. mixed cellular thymoma; 4. granulomatous thymoma
(is composed of atypical multinuclear cells with the formation of granulomatous
masses).
Pituitary tumors. Tumors of the anterior pituitary are more common than those
of the posterior pituitary and hypothalamus. The most common of the anterior pitui-
tary tumors are adenomas. They are conventionally classified according to their H&E
staining characteristics of granules into acidophil, basophil and chromophobe ade-
nomas. However, this morphologic classification is considered quite inadequate be-
cause of the significant functional characteristics of each type of adenoma including
the chromophobe adenoma, which on H&E staining doesnt show visible granules.
Modern classification of pituitary adenomas is based on functional features as corre-
lated with morphologic features of older classification. Thus, the types of this classi-
fication are the following: 1). Lactotroph adenoma; 2). Somatotroph adenoma; 3).
Mixed somatotroph-lactotroph adenoma; 4). Corticotroph adenoma; 5). Gonadotroph
adenoma; 6). Thyrotroph adenoma; 7). Oncocytoma; 8). Pleurihormonal adenoma.
Epiphysis. Pinealoma is a benign tumor which is composed of glandular epi-
thelium and neuroglia. The tumor causes metabolic and hormonal disturbances.
Endocrinal tumors of the pancreas (islet cell tumors) are rare as compared
with tumors of the exocrine pancreas. Islet cell tumors are generally small and may
be hormonally inactive or may produce hyperfunction. They may be benign or malig-
nant, single or multiple. They are named according to their histogenesis such as:
1. -cell tumor insulinoma. The tumor is composed of cords and
sheets of well-differentiated -cells which do not differ from normal cells.
The neoplastic cells secrete insulin into the blood stream which remains un-
affected by normal regulatory mechanisms. This results in characteristic at-
tacks of hypoglycaemia and high plasma insulin level.
2. G-cell tumor gastrinoma. Tumor cells produce hypergastrinae-
mia. Majority of gastrinomas occur in the wall of the duodenum. They may
be benign or malignant. Gastrinomas are associated with the development
of Zollinger-Ellison syndrome which is characterized by multiple peptic ul-
cers at usual sites such as the stomach and duodenum, or sometimes at unu-
sual sites such as in the oesophagus and jejunum.
3. A-cell tumor glucagonoma. The tumor causes hyperglycemia
and development of diabetes mellitus.
4. D-cell tumor somatostatinoma is characterized by hypoin-
sulinemia, hypoglucagonemia, steatorrhea and achlorhydria.
5. D1 cell tumor vipoma is characterized by hypopotassemia and
dehydration.
6. pancreatic polypeptide PP-secreting tumor
7. carcinoid tumor.
However, except insulinoma and gastrinoma, all others are extremely rare.
Carcinoid tumor is a generic term applied to tumors originating from endo-
crine cells belonging to APUD cell system and are therefore also called as apudomas.
The endocrine cells are distributed throughout the mucosa of the gastrointestinal
tract. Depending upon the embryologic derivation of the tissues where the tumour is
located, these are classified as foregut (stomach, duodenum and oesophagus), midgut
(terminal ileum and appendix), and hindgut (rectum and colon) carcinoids. Other un-
common locations are the bronchus, trachea, gallbladder, and Meckels diverticulum.
Appendiceal, ileal and stomach carcinoids behave as malignant tumors. Tumor cells
are monotonous, having uniform nuclei and are arranged in a variety of patterns
solid nests, sheets, cords, trabeculae and clusters.
TUMORS OF MELANIN-PRODUCING TISSUE

Melanin-producing cells (melanocytes) are of neurogenous origin. They may
be the origin of tumor-like formations (nevi) and melanomas.
Nevi are defects of development of neuroectodermal pigment elements. They
look like brown spots of different sizes, and may be either flat or elevated over the
surface or may be like warts. Sometimes their size is enormous (giant pigmented ne-
vus).
According to the WHO classification (1974), there are the following types of
nevi: 1) junction nevus, 2) compound nevus, 3) intradermal, 4) blue nevus, etc.
Junction nevus. Nests of nevus cells are found on the border of epidermis and
dermis.
Compound nevus. Together with the nevus cells located on the border of der-
mis and epidermis, there are nests of nevus cells in derma.
Intradermal nevus. Nevus cells are located only in derma. Some of them can be
found near the border between derma and epidermis. The nevus cells look like com-
pact mass. The cells in mature nevi may be multinuclear.
Blue nevus. Macroscopically this looks like bluish or bluish-brown (bluish-
gray) spot, its shape is round or oval, it does not elevate over the surface of the skin.
Microscopic examination reveals spindle-shaped melanocytes which are situated
deep in the derma.
Melanoma.
Melanoma is one of the most malignant tumors; it spreads through the lym-
phatic and hematogenous routes. 70% of melanomas develop in the skin of the face,
body and extremities.
Depending upon the clinical course and prognosis melanomas are of the fol-
lowing 4 types: 1). Superficial spreading melanoma; 2) Nodular melanoma; 3). Len-
tigo malign melanoma; 4). Acral lentigenous melanoma.
Some melanomas do not contain pigment. In the tumor, cells are pleomorphic,
usually there are a lot of mitoses in melanoma, and nodular type of melanoma is
characterized by hemorrhages and necroses. In the tumor decomposition, a great
amount of melanin and promelanin enter the bloodstream, which may be accompa-
nied by melaninemia and melaninuria. The tumors are localized on the skin, pigment
membrane of the eye, meninges, medullar layer of adrenal glands, and rarely in mu-
cous membranes.
TUMORS OF THE NERVOUS SYSTEM AND BRAIN COATS

Tumors of nervous system develop from different elements of the nervous sys-
tem: 1) central nervous system (CNS); 2) vegetative; 3) peripheral; 4) mesenchymal
elements, which are also a part of this system.
According to the degree of maturity, brain tumors may be more or less mature
(benign) or immature (malignant).
Special attention should be paid to the characteristic features of brain tumors.
1. The term benign is not suitable in this case as they are located in the brain and
indeed are always malignant. Even slow growth affects vitally important centers and
causes their dysfunction.
2. Neuroectodermal (neuroepithelial) tumors of brain originating from neuroecto-
derm derivatives are dysontogenetic, i.e. develop from the cells which are known as
precursors of mature CNS elements. Therefore, it may be difficult to determine their
histological type. More often their cellular composition corresponds to definite stages
of development of neuronal and glial elements.
3. Brain tumors produce metastases within the skull, which spread through the liquor.
Tumours of the CNS may originate in the brain or spinal cord (primary tu-
mours). Primary CNS tumours or intracranial tumours include: tumours arising from
constituent cells of the brain (with the sole exception of microglial cells) and from
the supporting tissues. Childhood brain tumours arise from more primitive cells (e.g.
neuroblastoma, medulloblastoma).
The classification of intracranial tumours abbreviated from the WHO classifi-
cation is the following:
I. TUMOURS OF NEUROGLIA (GLIOMAS)
1. Astrocytoma
2. Oligodendroglioma
3. Ependymoma
4. Choroid plexus papilloma
II. TUMOURS OF NEURONS
1. Neuroblastoma
2. Ganglioneuroblastoma
3. Ganglioneuroma
III. TUMOURS OF NEURONS AND NEUROGLIA
Ganglioglioma
IV.POORLY-DIFFERENTIATED AND EMBRYONAL TUMOURS
1. Medulloblastoma
2. Neuroblastoma
3. PNET (primitive neuroectodermal tumor)
V. TUMOURS OF MENINGES
1. Meningioma
2. Meningeal sarcoma
VI. NERVE SHEATH TUMOURS
1. Schwannoma (neurilemmoma)
2. Neurofibroma
3. Malignant nerve sheath tumour
Gliomas
The term glioma is used for all tumours arising from neuroglia, or more pre-
cisely, from neuroectodermal epithelial tissue. They include tumours arising:
- from astrocytes (astrocytomas and glioblastoma multiforme);
- from oligodendrocytes (oligodendroglioma);
- from ependyma (ependymoma);
- from choroid plexus (choroid plexus papilloma).
Gliomas may be well-differentiated or poorly-differentiated. However, gliomas
are never truly well-demarcated or encapsulated and thus all grades of gliomas infil-
trate the adjacent brain tissue.
Astrocytomas are the most common type of gliomas. They have a tendency to
progress from low grade to higher grades of anaplasia. Low-grade astrocytomas
evolve slowly over several years whereas higher grades (anaplastic astrocytoma and
glioblastoma multiforme) bring about rapid clinical deterioration of the patient.
Pathologically, astrocytomas have been conventionally divided into 3 progres-
sive histologic grades: fibrillary (most common), gemistocytic and protoplasmic.
However, currently WHO classification of astrocytomas is widely used which divides
them into 4 grades from grade I (low grade) to grade IV (glioblastoma multiforme).
WHO Grade I Astrocytoma: Juvenile pilocytic astrocytoma, pleomorphic xan-
thoastrocytoma.
WHO Grade II Astrocytoma: fibrillary, protoplastic, gemistocytic astrocytoma.
WHO Grade III Astrocytoma: anaplastic astrocytoma.
WHO Grade IV Astrocytoma: glioblastoma multiforme.
Oligodendroglioma is an uncommon glioma of oligodendroglial origin and
may develop in isolation or may be mixed with other glial cells. X-ray examination
and CT scan reveal a well-defined mass with numerous small foci of calcification.
The tumour is generally slow-growing.
Ependymoma is not an uncommon tumour, derived from the layer of epitheli-
um that lines the ventricles and the central canal of the spinal cord. It occurs chiefly
in children and young adults (below 20 years of age). Typically, it is encountered in
the fourth ventricle (posterior fossa tumour). Other locations are the lateral ventricles,
the third ventricle, and in the case of adults, the spinal cord in the region of lumbar
spine. The usual biologic behavior is of a slow-growing tumour over a period of
years.
Neuronal tumors
Ganglioneuroma is a rare mature tumor. Most frequently it is localized near the
3rd ventricle, less often in the hemispheres of the brain. It usually occurs in children
and adolescents. The tumor consists of mature ganglionic cells separated with the
bands of glial stroma. Macroscopically, ganglioneuroma looks like a circumscribed
node. In the medulla oblongata it is diffuse, in the cerebellum it looks like hyperplas-
tic folds.
Cerebellum ganglioma is characterized by proliferation of large nervous ele-
ments of Purkinje's cell type.
Ganglioneuroblastoma is a malignant counterpart of ganglioneuroma (malig-
nant gangliocytoma). This is an extremely rare tumor of CNS. It is characterized by
cellular polymorphism.
Neuroblastoma is a rare highly malignant brain tumor. It occurs mainly in chil-
dren. The tumor is formed from large cells with bubble-like nucleus. Mitoses are nu-
merous. The cells grow like syncytium.
Poorly-differentiated and embryonal tumours
CNS tumours composed of primitive undifferentiated cells include medullo-
blastoma and glioblastoma.
Medulloblastoma is the most common variety of primitive neuroectodermal
tumour. It occurs in patients over the age of 20 years. The most common location is
the cerebellum in the region of the roof of the fourth ventricle, in the midline of cere-
bellum, in the vermis, and in the cerebellar hemispheres. Medulloblastoma is a highly
malignant tumour and spreads to local as well as to distant sites. It invades locally
and by the cerebrospinal fluid to meninges, ventricles and subarachnoid space and
has a tendency for widespread metastases to extraneural sites such as to lungs, liver,
vertebrae and pelvis.
Tumours of meninges
The most common tumour arising from the pia-arachnoid is meningioma ac-
counting for 20% of intracranial tumours.
Meningiomas arise from the cap cell layer of the arachnoid. Their most com-
mon sites are in the front half of the head and include: lateral cerebral convexities,
midline along the falx cerebri adjacent to the major venous sinuses parasagittally, and
olfactory groove. Less frequent sites are: within the cerebral ventricles, foramen
magnum, cerebellopontine angle and the spinal cord. They are usually found in the
2nd to 6th decades of life, with slight female preponderance. Most meningiomas are
benign and can be removed successfully. Rarely, a malignant meningioma may me-
tastasise, mainly to the lungs.
Grossly, meningioma is well-circumscribed, solid, spherical or hemispherical
mass of varying size (1-10 cm in diameter). The tumour is generally firmly attached
to the dura and indents the surface of the brain but rarely ever invades it.
Microscopically, meningiomas are divided into 5 subtypes: meningothelioma-
tous (syncytial), fibrous (fibroblastic), transitional (mixed), angioblastic and anaplas-
tic (malignant).
Nerve sheath tumours
Tumours of the peripheral nerves are commonly benign and include schwan-
noma (neurilemmoma) and neurofibroma. Both of them arise from Schwann cells but
neurofibroma contains large amount of collagen. Rarely, their malignant counterpart,
malignant peripheral nerve sheath tumour, develops particularly in patients with von
Recklinghausen's neurofibromatosis.
Microscopically, schwannoma is composed of fibrocellular bundles forming
whorled pattern. There are areas of dense and compact cellularity alternating with
loose acellular areas. Areas of pattern show palisaded nuclei called Verocay bodies.
Neurofibromas may occur as solitary, fusiform cutaneous tumour of a single
nerve, but more often are multiple associated with von Recklinghausen's disease. Mi-
croscopically, a neurofibroma is composed of bundles and interlacing fascicles of
delicate and elongated spindle-shaped cells having wavy nuclei.
Malignant peripheral nerve sheath tumor is a poorly differentiated spindle cell
sarcoma of the peripheral nerves occurring most often in adults.
Tumors of vegetative nervous system originate from ganglionic cells of differ-
ent degree of maturity (sympathogonias, sympathoblasts, ganglioneurocytes) in sym-
pathetic ganglia as well as from the cells of nonchromophinic paraganglia (glomes)
genetically associated with sympathetic nervous system. Such benign tumors as gan-
glioneuroma, paraganglioma (glome tumor, chemodentoma) belong to this group.
3. Class work.

326 Papilloma of skin The skin surface shows papillary growth with a
pedicle. Grossly, tumor resembles cauliflower.
331 Carcinoma of skin The skin surface shows an ulcerated growth with
elevated and indurated margin.
27 Carcinoma of esophagus In the middle third of the esophagus there is
an infiltrating tumor with ulceration which invades the bronchial wall and is compli-
cated by trachea-esophageal fistula formation (shown in the preparation by the glass
tube).
37 Saucer-shaped carcinoma of stomach The tumor resembles a saucer:
it has a round shape, flat bottom, and elevated margin.
319 Carcinoma of breast Pay attention to the orange-like skin phenome-
non, retraction of the nipple and ulceration of the skin above the tumor.
320 Carcinoma of mammary gland nipple The nipple bears a crusted,
scaly eczematoid lesion.
312 Carcinoma of uterus neck Pay attention to the poorly-circumscribed
tumor with invasive growth and destruction of the uterus cervix.
317 Carcinoma of ovary Tumor looks as a cyst with thick walls.
310 Papillary cystadenoma of ovary Pay attention to the everted cyst
with intracystic papillary projections on the internal surface which are fixed to the
thin wall of the cyst.
308 Choriocarcinoma Find a haemorrhagic, soft and fleshy mass in the
uterine cavity.
282, 283 Tumors of brain Tumors have irregular shape, poorly-
circumscribed borders, variegated appearance and invasive growth.
285 Tumor of spinal cord Find a circumscribed tumor in the spinal cord
which is solid and whitish-grey.
80 Papilloma of skin. (hematoxylin and eosin staining). Study the tumor

structure (find the parenchyma (a) and stroma (b)). Pay attention to cells complexity,
degree of tissue atypia and correlation of parenchyma and stroma, presence of in-
flammation in tumor. Draw.
b
96 Squamous cell carcinoma. (hematoxylin and eosin staining). Pay at-
tention to the correlation of parenchyma and stroma, degree of tissue atypia, tumor
invasion, and foci of destruction. Note the degree of cellular atypia, absence of base-
ment membrane, migratory cancerous pearls (a). Draw.
84 Papillary cystic adenoma of ovary. (hematoxylin and eosin staining).

The wall of the cyst consists of fibrous connective tissue. Internal coat is lined by cy-
lindrical epithelium with stromal papillae, with epithelium proliferation in some re-
gions. Draw.
130 Choriocarcinoma. (hematoxylin and eosin staining). Tumor consists
of mononuclear cytotrophoblast cells large light bizarre pleomorphic cells
(Langhans`s cells) (figure A) and dark bizarre syncytiotrophoblast (figure B four
cells) cells with multiple irregular and hyperchromatic nuclei. Pay attention to tumor
invasive growth in myometrium. Spaces between the cells are filled with blood clots
and leucocytes accumulation (figure A, red arrows).
A B
158 Carcinoid tumor of stomach. (hematoxylin and eosin staining). Tu-

mor (A) looks like a node in the mucous and submucous coats. It contains uniform
small cells, formatting cords, solid complexes with alveolar structures, rosettes.
Draw.
A
95 Metastasi of melanoma in the liver. (hematoxylin and eosin staining).
Among the hepatocytes (red arrow) in the liver there are large cells with cellular pol-
ymorphism and brown pigment accumulation (black arrow) in the cytoplasm and
small rather monomorphous tumor cells free of pigment (a).
89 Melanoma of skin. (hematoxylin and eosin staining). There are

groups of polymorphic tumor cells containing brown pigment in the cytoplasm in the
basal layers of squamous epithelium and derma (arrows).
89 Melanoma of eyeball. (hematoxylin and eosin staining). There are
retinal structures in the preparation with thickening of the pigmented layer due to pro-
liferation of polymorphic cells, which contain brown pigment in their cytoplasm
(melanin).
III. Complete the tables (see theoretical part)
Tumors of nervous system and brain coats.

Cell origin Benign tumors Malignant tumors
Astrocyte Astrocytoma Anaplastic astrocytoma
Epithelial tumors without specific localization.

Tumor source Benign tumors Malignant tumors
Stratified epithelium Papilloma Squamous cancer with keratinization and
without keratinization
Tumors of endocrine glands and epithelial tissues

Tumor origin Benign tumors Malignant tumors
Liver: hepatocytes Adenoma (hepatoma) Hepatocellular carcinoma
Tumors of endocrine glands

Tumor origin Benign tumors Malignant tumors
Ovary:
1. surface epithelium Serous cystadenoma, mucin- Serous cystadenocarcinoma; mucinous
ous cystadenoma cystadenocarcinoma, endometrioid
adenocarcinoma
4. Clinical tasks.
1. A 77-year-old man has a small protruding mass on the skin of his face. On histo-
logical examination, basal cell carcinoma was diagnosed.
1. What physical factor can provoke the development of this tumor?
2. What type of growth has this tumor?
3. Does this tumor metastasize?
4. What is the synonym of this tumor?
2. On examination of a skin biopsy, a tumor composed of epidermal irregular com-

plexes with features of high cellular atypia and multiple mitoses was revealed in the
derma. A whorled arrangement of pinkish laminated material forming keratin pearls
was found in the centers of the complexes.
1. Is the revealed tumor benign or malignant? What is the histogenesis of this
tumor?
2. What type of growth has this tumor?
3. In what other organs can such tumor be revealed?
4. What is the reason for keratin pearls formation in the tumor? What is the syn-
onym of horn pearls?
3. On nephrosonography of a 47-year-old patient who had hematuria a round shape

node invading its capsule was revealed in the upper pole of the right kidney. The di-
ameter of the node was 5 cm. A nephrectomy was made. Grossly the node had flaccid
consistency and golden yellow color.
1. What tumor was revealed in the kidney?
2. What is the reason for the golden yellow color of the tumor tissue?
3. What is the histogenesis of this tumor?
4. Characterize microscopic features of this tumor.
4. One year after having a spontaneous abortion a 28-year-old woman presented

with hemoptysis. On computed tomographic scanning, several tumor nodes which
were regarded as metastases were revealed in her lungs. The level of beta-hCG (hu-
man chorionic gonadotrophin) was severely increased.
1. What is the localization of the primary tumor node?
2. What is the name of the tumor?
3. What is the cell origin of this tumor?
4. What is the predominant route of the tumor metastases?
5. On computed tomographic scanning, a nodular mass in the parietal lobe of the

left cerebral hemisphere of a 45-year-old man was revealed. He was treated surgical-
ly. The tumor was situated in the white matter of the brain in the form of a soft varie-
gated poorly circumscribed node of irregular shape which had no apparent connection
with the meninges. On histological examination, glioblastoma was diagnosed.
1. What is the cell origin of this tumor?
2. What low-grade (benign) tumor may precede the development of glioblasto-
ma?
3. What is the reason for variegated appearance of this tumor?
4. What metastasizing characteristics has this tumor?
ANSWERS
1 2 3 4
1 Insolation Locally destructive No Basalioma
(ultraviolet
radiation)
2 Malignant tumor Invasive (infiltrative) Lungs, larynx, oral Keratin pearls formation in
squamous cell growth cavity, esophagus, the tumor is caused by ex-
carcinoma uterine cervix, vagina tracellular keratin for-
mation. Cancer pearls
3 Renal cell carci- Golden yellow color Epithelium of renal The tumor microscopically
noma (clear cell of the tumor tissue is tubules is composed of irregular
variant) caused by presence cells with clear (optically
of lipids in the cyto- void) cytoplasm and small
plasm of tumor cells hyperchromic round nuclei
4 Uterus Choriocarcinoma Trophoblast (epitheli- Hematogenous
um of chorionic villi)
5 Neuroepithelial Astrocytoma Variegated appearance Spreading (metastasis) via
tumor of this tumor is caused cerebrospinal fluid within
by necroses and hem- the CNS
orrhages
5. Self assessment.
1. 2. Cytokines secreted by tumors that induce angiogenesis and assist the
tumor in establishing its blood supply include all of the following,
EXCEPT:
1. Tumor necrosis factor
2. Fibroblast growth factor
3. Transforming growth factor-
4. Transforming growth factor-
5. Platelet-derived growth factor
2. 3. All of the following types of molecule can directly control cell growth,
EXCEPT:
1. Cyclins
2. Ras proteins
3. G proteins
4. Mitogen-activated protein kinases
5. Selectins
3. 7. All of the following genes (known as tumor suppressor genes) pro-
vide the negative control over cell proliferation, EXCEPT:
1. p53
2. DCC (deleted in colon cancer)
3. Rb
4. WT-1
5. bcl-2
4. 17. All of the following statements correctly describe cell oncogenes,
EXCEPT:
1. Oncogenes are derived from viral DNA that has been incorporated into the
genome
2. Oncogenes encode proteins that resemble the products of normal genes
3. Some oncogene products are the analogues of growth factors
4. Some oncogene products are the analogues of growth factor receptors
5. Some oncogene products activate nuclear transcription
5. 13. All of the following viruses proved to be capable of producing malig-
nancies in human beings, EXCEPT:
1. Human papillomavirus
2. Cytomegalovirus
3. Epstein-Barr virus
4. Hepatitis B virus
5. Hepatitis C virus
6. 10. Lack of differentiation is characteristic of the:
1. Hyperplasia
2. Hypoplasia
3. Anaplasia
4. Hypertrophy
5. Dysplasia
7. Lesion representing benign neoplasia is:
1. Chondroblastic osteosarcoma of the bone
2. Granuloma of the soft tissue
3. Tuberculoma
4. Papillary serous cystadenoma of the ovary
5. Papillary carcinoma of the thyroid gland
8. The most characteristic manifestation of malignant tumor is:
1. Cellular atypia and pleomorphism
2. Compression of surrounding tissue
3. Large size
4. Necrosis
5. Metastases
9. The most characteristic feature of malignant neoplasm in contrast to a
reactive or inflammatory overgrowth:
1. Growth factor production
2. Necrosis
3. Localization
4. Autonomous growth following the removal of all provoking factors
5. Adjacent tissue compression
10. The factor assessed in the histological grading of a malignant tumor:
1. The number of lymph node metastases
2. The size (diameter) of the primary tumor
3. The extent of invasion of the primary tumor into surrounding structures
4. The degree of cytological differentiation of the primary tumor
5. The presence or absence of liver metastases
11. The term of a benign epithelial tumor is constructed by combining the
word designating the tumor cell origin plus the ending:
1. -sarcoma
2. -carcinoma
3. -itis
4. -oma
5. -osis (-asis)
12. Carcinomas with epidermoid cell differentiation are called:
1. Sarcomas
2. Adenocarcinomas
3. Squamous cell carcinomas
4. Papillomas
5. Cystadenomas
13. Carcinomas forming glandular structures are called:
1. Sarcomas
2. Papillomas
3. Adenocarcinomas
4. Cystadenomas
5. Polyps
14. All of the following morphologic features characterize adenocarcinoma
cells, EXCEPT:
1. Variation in size and shape
2. Hyperchromatic nuclei
3. Enlarged nucleoli
4. Hypochromatic nuclei
5. Atypical mitoses
15. The first site of metastasis for adenocarcinoma of the colon is most like-
ly to the:
1. Brain
2. Liver
3. Lung
4. Lymph nodes
5. Spleen
16. A tumor that tends to spread over the surfaces of organs or body cavi-
ties rather than metastasizing via blood vessels or lymphatics:
1. Colon carcinoma
2. Thyroid carcinoma
3. Mesothelioma
4. Renal cell carcinoma
5. Hepatocellular carcinoma
17. Lesion of the female genital tract considered precancerous:
1. Cystic atrophy of the endometrium
2. Endocervical polyps
3. Condyloma acuminatum of the vulva
4. Endometrial polyps
5. Atypical hyperplasia of the endometrium
18. Most common benign tumor of the ovary:
1. Papilloma
2. Fibroma
3. Cystadenoma
4. Adenocarcinoma
5. Melanoma
19. Most common benign tumor of the female breast:
1. Cystadenoma
2. Fibroadenoma
3. Sarcoma
4. Fibroma
5. Adenocarcinoma
20. Poor prognosis in breast cancer is associated with all of the following,
EXCEPT:
1. Overexpression of the erbB2/neu oncogene
2. Absence of estrogen receptors
3. Presence of aneuploidy
4. Extensive angiogenesis
5. Overexpression of the N-myc oncogene
ANSWERS
1 1 11 4
2 5 12 3
3 5 13 3
4 1 14 4
5 2 15 4
6 3 16 3
7 4 17 5
8 5 18 3
9 4 19 2
10 4 20 5
Class 13
Theme: NEOPALSMIC DISORDERS OF BLOOD AND LYMPHOID
ORGANS
1. Scheme of normal hemopoiesis.
2. Classification of hematologic and lymphatic tissues neoplasms.
3. Acute leukemia: types, morphology, clinical feature, damages to organs.
4. Chronic leukemia: types, morphology, clinical feature, damages to organs.
5. Regional tumor diseases of lymphoreticular origin.
LEUKAEMIAS
Definition and classification. The leukaemias are a group of disorders charac-
terized by malignant transformation of blood-forming cells.
The proliferation of leukaemic cells takes place primarily in the bone marrow,
and in certain forms, in the lymphoid tissue (in spleen or lymph nodes, etc.). Ulti-
mately, the abnormal cells appear in the peripheral blood raising the total white cell
count to high level. The features of bone marrow failure (e.g., anaemia, thrombocy-
topenia, neutropenia) and involvement of other organs (e.g., liver, spleen, lymph
nodes, meninges, brain, skin etc) occur.
In general, leukaemias are classified on the basis of cell types predominantly
involved, into myeloid and lymphoid, and on the basis of natural history of the dis-
ease, into acute (with the proliferation of blast, nondifferentiated cells) and chronic
(with the proliferation of differentiated cells, relatively benign duration). Thus, the
main types are: acute myeloblastic and acute lymphoblastic (AML and ALL), and
chronic myeloid and chronic lymphocytic leukaemias (CML and CLL); hairy cell
leukaemia (HCL) is an unusual variant of lymphoid neoplasia.
According to impairment in formula of peripheral blood there are the following
forms of leukaemias:
1. leukemic leukaemias (in 1ML of blood there are 100 000 of leukemic cells),
2. subleukemic leukaemias (in 1ML of blood there are 15 000-25 000 of leu-
kemic cells),
3. leucopenic leukaemias (general number of white blood cells is decreased,
but tumor cells appear).
4. aleucemic leukaemias (in peripheral blood tumor cells are absent).
The leukaemia arises following malignant transformation of a single clone of

cells belonging to myeloid or lymphoid series, followed by proliferation of the trans-
formed clone. The evolution of leukaemia is multi-step process, and in many cases,
acute leukaemia may develop after a pre-existing myelodysplastic or myeloprolifera-
tive disorder.
Distinctive features of acute and chronic leukaemias are:

1. Bone marrow and blood picture (in acute leukemia blasts are observed, in chronic
leukemia mature cells are found).
2. Leukemic failure (hiatus leucemicus) characterizes acute leukemia. It is severe in-
crease of blast count and single mature elements while intermediate forms are absent.
3. High grade enlargement of the spleen, liver, kidneys and lymphatic nodes charac-
terizes chronic leukemia while in acute leukemia it has fewer grades. The spleen can
weigh 6-8 kg, the liver 5-6 kg.
Complications and causes of death: 1) hemorrhage into vitally important or-
gans (e.g. brain); 2) ulcerative, necrotic and septic complications (sepsis).
Acute leukaemias are characterised by the predominance of undifferentiated

leucocyte precursors or leukaemic blasts. Acute leukaemias may be derived from the
myeloid stem cells (acute myeloblastic leukaemia (AML)), or from the lymphoid stem
cells (acute lymphoblastic leukaemia (ALL)).
More definite criteria for diagnosis and classification of acute leukaemias have
been laid down by a group of French, American and British haematologists common-
ly called the FAB classification. According to this system, a leukaemia is acute if the
bone marrow consists of more than 30% blasts.
The most frequent types of acute leucaemias are:
1. acute undifferentiated,
2. acute myeloblastic,
3. acute lymphoblastic,
4. acute plasmoblastic,
5. acute monoblastic,
6. acute myelomonoblastic,
7. acute erythromyeloblastic,
8. acute megakaryoblastic.
Manifestations of acute leukaemias are divided into 2 groups: those due to

bone marrow failure, and those due to organ infiltration.
I. Due to bone marrow failure. These are some syndromes:
1. Anaemia producing pallor, lethargy, dyspnoea.
2. Bleeding manifestations due to thrombocytopenia: spontaneous bruises, pe-
techia, and other bleeding tendencies.
3. Infections are quite common and include those of mouth, throat, skin, respir-
atory, perianal and other sites.
4. Fever is generally attributed to infections in acute leukaemia but sometimes
no obvious source of infection can be found and may occur in the absence of infec-
tion.
II. Due to organ infiltration. The clinical manifestations of acute leukaemia are
more often due to replacement of the marrow and other tissues by leukaemic cells.
These features are as under:
1. Pain and tenderness of bones (e.g. sternal tenderness) are due to bone in-
farcts or subperiosteal infiltrates by leukaemic cells. These features are more frequent
in children with ALL.
2. Lymphadenopathy and enlargement of the tonsils are more common in ALL.
3. Splenomegaly of moderate grade is common, especially in ALL. Splenic in-
farction, subcapsular haemorrhages, and rarely, splenic rupture may occur.
4. Hepatomegaly is frequently present due to leukaemic infiltration but the in-
filtrates usually do not interfere with the function of the liver.
5. Leukaemic infiltration of the kidney may be present and ordinarily does not
interfere with its function unless secondary complications such as haemorrhage or
blockage of ureter supervene.
6. Gum hvpertrophy due to leukaemic infiltration of the gingivae is a frequent
finding in myelomonocytic (M4) and monocytic (M5) leukaemias.
7. Chloromas are localised tumour-forming masses occurring in the skin or or-
bit due to local infiltration of the tissues by leukaemic cells. They are greenish in ap-
pearance due to the presence of myeloperoxidase.
8. Meningeal involvement manifested by raised intra-cranial pressure, head-
ache, nausea and vomiting, blurring of vision and diplopia are seen more frequently
in ALL during haematologic remission. Sudden death from massive intracranial
haemorrhage as a result of leucostasis may occur.
9. Other organ infiltrations include testicular swelling in ALL and mediastinal
compression in T cell type ALL.
Chronic leukaemias are those haematologic malignancies in which the pre-

dominant leucemic cells are initially well-differentiated and easily recognisable as
regards their cell type.
Chronic leukaemias are divided into 2 main types: chronic myeloid (granulo-
cytic) leukaemia (CML or CGL), and chronic lymphocytic leukaemia (CLL). Less
common variants include: chronic eosinophilic, chronic basophilic, chronic monocyt-
ic, chronic neutrophilic and chronic lymphosarcoma cell leukaemias. An unusual
chronic lymphoproliferative variant is hairy cell leukaemia (HCL). In general, chron-
ic leukaemias have a better prognosis than the acute leukaemias.
CHRONIC MYELOID LEUKAEMIA (CML)
Chronic myeloid (myelogenous, granulocytic) leukaemia comprises about 20%
of all leukaemias and its peak incidence is seen in 3rd and 4th decades of life.
Manifestations
The onset of CML is generally insidious. Some of the common presenting
manifestations are as under:
1. Features of anaemia such as weakness, pallor, dyspnoea and tachycardia.
2. Symptoms due to hypermetabolism such as weight loss, lassitude, anorexia,
night sweats.
3. Splenomegaly is almost always present and is frequently massive. In some
patients, it may be associated with acute pain due to splenic infarction.
4. Bleeding tendencies such as easy bruising, epistaxis, menorrhagia and hae-
matomas may occur.
5. Less commonly, features such as gout, visual disturbance, neurologic mani-
festations and priapism are present.
6. Juvenile CML is more often associated with lymph node enlargement than
splenomegaly. Other features are frequent infections, haemorrhagic manifestations
and facial rash.
CHRONIC LYMPHOCYTIC LEUKAEMIA (CLL)
Chronic lymphocytic leukaemia constitutes about 25% of all leukaemias and is
predominantly a disease of the elderly (over 50 years of age) with a male preponder-
ance (male-female ratio 2:1).
Manifestations
The onset of disease is characteristically insidious. Common presenting mani-
festations are as under:
1. Features of anaemia such as gradually increasing weakness, fatigue and
dyspnoea
2. Enlargement of superficial lymph nodes is a very common finding. The
lymph nodes are usually symmetrically enlarged, discrete and non-tender.
3. Splenomegaly and hepatomegaly are usual.
4. Haemorrhagic manifestations are found in case of CLL with thrombocyto-
penia.
5. Infections, particularly of respiratory tract, are common in CLL.
6. Less common are: mediastinal pressure, tonsillar enlargement, disturbed vi-
sion, and bone and joint pains.
PLASMA CELL DISORDERS. The plasma cell disorders are characterized by
abnormal proliferation of immunoglobulin-producing cells and result in accumulation
of monoclonal immunoglobulin in serum and urine. The group as a whole is known
by various synonyms such as plasma cell dyscrasias, paraproteinaemias, dyspro-
teinaemias and monoclonal gammopathies. The group comprises the following four
disease entities:
1. Multiple myeloma
2. Waldenstrom's macroglobulinaemia
3. Heavy chain disease
4. Primary amyloidosis.
The feature common to all plasma cell disorders is the neoplastic proliferation
of cells derived from B-lymphocyte lineage. Normally, B lymphocytes have surface
immunoglobulin molecules of both M and G heavy chains. Under normal circum-
stances, the B-cells are stimulated by exposure to surface immunoglobulin-specific
antigen and mature to form IgG-producing plasma cells. However, in the plasma cell
disorders, the control over this process is lost and results in abnormal production of
immunoglobulin that appears in the blood and urine. These disorders differ from B-
cell lymphomas in having monoclonal synthesis, of immunoglobulins and lack of
prominent lymphadenopathy. In addition to the rise in complete immunoglobulins,
some plasma cell disorders synthesize excess of light chains (kappa or lambda), or
heavy chains of a single class (alpha, gamma, or mu). Bence Jones proteins are free
light chains present in blood and excreted in urine of some cases with plasma cell
disorders.
Flat bones (ribs and skull) are the most frequently involved, tubular bones
(humerus and femur) are involved less frequently. Focal resorption of the bone in the
places of tumor growth results in osteolysis and osteoporosis. The bones become
fragile. Hypercalcemia develops due to their damage; it may be followed by devel-
opment of calcium metastases. Tumor cell infiltration develops in the visceral organs:
spleen, lymphatic nodes, liver, kidneys, lungs, etc. A number of changes is caused by
secretion of paraproteins by the tumor cells. These changes are amyloidosis,
paraproteinemic nephrosis or myeloma nephropathy resulting in contracted kidney.
Depending on the maturation of myeloma cells, myelomas are divided into: 1)
plasmocyte, 2) plasmoblast, 3) polymorphocellular, 4) small cellular.
Morphologically, depending on the character of myeloma infiltrations the fol-
lowing forms are defined: 1) diffuse, 2) diffuse nodular, 3) multiple nodular, 4) soli-
tary.
Causes of death: uremia, sepsis, amyloidosis, paraproteinemic coma.
LYMPHOMAS are malignant tumours of lymphoreticular origin i.e. from

lymphocytes and histiocytes and their precursor cells. Clinically and pathologically,
lymphomas are quite heterogeneous. However, two distinct clinicopathologic groups
are routinely distinguished:
I. Hodgkin's lymphoma or Hodgkin's disease (HD) characterised by pathogno-
monic presence of Reed-Sternberg cells. This group comprises about 25% of all cases
of malignant lymphoma. There are 4 subtypes of HD:
1. Lymphocyte-predominance type.
2. Nodular-sclerosis type.
3. Mixed-cellularity type.
4. Lymphocyte-depletion type.
II. Non-Hodgkin's lymphomas (NHL) are more common and comprise the rest
of cases.
Non-Hodgkin's lymphomas (NHL) are the malignant neoplasms of the immune
system of the body and are more common than Hodgkin's lymphoma. The biologic
and clinical behaviour of NHL are quite distinct from HD and thus the two are quite
different diseases. NHL is most frequent in young adults (20-40 years). Its incidence
is showing an upward trend due to increasing incidence of AIDS.
There are several classifications of lymphomas. International Lymphoma
Study Group in 1994 has proposed a classification called revised European-American
classification of lymphoid neoplasms abbreviated as R.E.A.L. classification. This
classification is based on the hypothesis that all forms of lymphoid malignancies
(NHLs as well as lymphoblastic leukaemias) represent malignant counterparts of
normal population of immune cells (B-cells, T-cells and histiocytes) present in the
lymph node and bone marrow. It is believed that lymphoid malignancies arise due to
arrest at the various differentiation stages of B and T-cells since tumours of histio-
cytic origin are quite uncommon. Accordingly, it is considered essential to under-
stand and correlate the differentiation stages of B and T-cells with various lymphoid
malignancies. R.E.A.L. classification divides all lymphoid malignancies into two
broad groups, each having further subtypes:
Leukaemias and lymphomas of B-cell origin: B-cell derivation comprises
80% cases of lymphoid leukaemias and 90% cases of NHLs. Based upon these phe-
notypic and genotypic features, B-cell neoplasms are of pre-B and mature B-cell
origin. Based on their biologic behaviour, B-cell malignancies are further subclassi-
fied into indolent and aggressive. All these tumours express Pan-B (CD19) antigen
besides other markers.
Leukaemias and lymphomas of T-cell origin: T-cell malignancies comprise
the remainder 20% cases of lymphoid leukaemia and 10% cases of NHLs. T-cell ma-
lignancies reflect the stages of T-cell ontogeny. Like B-cell malignancies, T-cell de-
rivatives too are further categorised into indolent and aggressive T-cell malignancies.
The most widely expressed T-cell antigens are CD2 and CD7.
3. Class work.

257 Spleen in lymphogranulomatosis. Spleen is enlarged, has a firm
consistence, its cut surface has red color with a lot of small white-yellow foci (por-
phyritic spleen).
253, 255 Spleen in leukemia. Spleen is enlarged, red, has a firm consist-
ence.
288 Multiple myeloma (bones of skull). Find dark foci of bone tissue de-
struction which size is from 0.5 to 2.0 cm. Explain their occurrence.
101 Liver in myeloid leucosis. (hematoxylin and eosin staining). Note

leucemic infiltrate localization (lobulus, portal tracts - arrows), study cells of infiltrate
using high magnification, and evaluate the degree of their differentiation, define the
type of hepatocytes dystrophy. Draw.
69 Lymphogranulomatosis of lymph node. (hematoxylin and eosin
staining). Using small magnification, pay attention to absence of normal lymph node
structure and replacement of lymphoid tissue by tumor tissue with foci of necrosis
and sclerosis. Study tumor cells using high magnification, find diagnostic cells (ar-
rows), define the histological variant of lymphogranulomatosis. Draw.
III. Complete the tables
Acute leukemia
Acute leukemia Damages to organs
type Bone marrow Lymph nodes/ Liver Spleen Kidney
tonsils
Acute undifferen- Red or pyoid, Slightly en- Slightly en- Slightly en- Slightly
tiated leukemia larged, infiltrat- larged, infil- larged, infil- enlarged,
ed with leuke- trated with trated with infiltrated
mic leukemic cells leukemic with leu-
cells/necrotic cells kemic cells
tonsilitis
Types of chronic leukemia

Types of leukemia Internal organ damage Outcomes and complications
Chronic lymphocyt- Anemia fatty dystrophy of parenchymal Susceptibility to infections with
ic leukemia cells, bone marrow is red with yellow foci, infectious complications, com-
lymph nodes enlargement of high grade, pression of internal organs by en-
splenomegaly of high grade, hepatomegaly, larged lymph nodes, hemorrhagic
haemorrhagic manifestations, autoimmune and hemolytic (jaundice, haemo-
reactions, enlargement of kidneys siderosis) complications
4. Clinical tasks.
1. A 4-year-old child had low grade fever, hemorrhages in mucous membranes, na-
sal bleeding, weakness, pain and tenderness of shin, sore throat. On examination of
the patient, enlargement of lymph nodes, thymus, spleen, liver and necrotic tonsillitis
were revealed. There was an increase in lymphoid cells count (mainly lymphoblasts)
up to 25 000 in 1 l of blood in routine hematologic investigation. An examination of
bone marrow revealed presence of more than 60% of blasts.
The patient died of hemorrhage into the brain.
At autopsy, high grade enlargement of lymph nodes, thymus and spleen were diag-
nosed. The bone marrow of tubular and flat bones was crimson-red.
1. What is the type of leukemia according to clinical findings, cytogenesis and
level of tumor cells differentiation?
2. What is the pathogenesis of hemorrhagic diathesis and hemorrhage in brain?
3. What is the reason for enlargement of lymph nodes, thymus and spleen?
2. A 45-year-old man had an increased leukocytes count up to 25 000/l with the

appearance of myelocytes and promyelocytes in routine blood picture, anemia, en-
largement of spleen, and weakness. Conservative therapy helped the patient. Howev-
er, after 2 years, the status of the patient worsened. Fever, weakness, hemorrhagic
diathesis, anemia, marked enlargement of spleen developed. The therapy was failed,
the patient died.
At autopsy, the bone marrow of tubular and flat bones was grey-red and pyoid. On
microscopical examination myelocytes, promyelocytes and blast cells were revealed
in the bone marrow. The blood was grey-red, the visceral organs were anemic. There
was marked enlargement of the spleen, which weighed 6 kg. On cutting, the spleen
was dark red with ischemic infarctions. Its tissue was replaced by leukemic infiltrate.
There were leukemic thrombi in blood vessels of the patient. There was marked en-
largement of the liver (up to 5 kg) with leukemic infiltrates in its sinusoids. Lymph
nodes were enlarged. Group and solitary follicles were found in the lymph nodes as
well as in the tonsillar tissues. Leukemic infiltration was found in the kidneys, skin
and meninges.
1. What is the type of leukemia?
2. What was the phase of the disease according to the appearance of blasts in
blood?
3. What was the reason for splenomegaly, hepatomegaly and enlargement of
lymph nodes?
3. A 50-year-old man with weakness and sweating developed renal failure.

At autopsy, anemia, foci of injury in bones of skull and in vertebrae were found.
The latter morphologically were presented by osteoporosis and tumor tissue which
was composed of plasma cells, plasma blasts and pleomorphic cells. Liver, spleen
and kidneys had amyloid depositions; there were inflammatory foci in the lungs.
1. What is the name of the presented disease? What group of leukemia does this
tumor belong to?
2. Where do primary lesions arise in this disease?
3. What pathological changes occur in primary foci?
4. What pathologic substances do tumor cells secrete?
5. What is the reason for nephropathy?
4. A 25-year-old woman had fever, sweating, weight loss. After a while a retroster-
nal pain appeared. Physical examination revealed enlargement of cervical and sub-
clavicular lymph nodes. After some time, marked enlargement of mediastinal lymph
nodes was diagnosed on X-ray examination. Later the patient developed cough,
dyspnea, and symptoms of cervical veins compression. A biopsy of the cervical
lymph nodes was made. On histological examination, the normal structure of lymph
nodes was damaged due to proliferation of lymphoid polymorphous cells, such as
eosinophils, neutrophils, plasma cells and fibroblasts. There were multinuclear giant
cells with hyperchromic and pale popcorn like nuclei among these cells. The woman
died of endogenous intoxication progression.
At autopsy, lymph nodes of the neck, mediastinum and retroperitoneal space were
markedly enlarged with the histological changes described above. The spleen was
enlarged too with dark red pulp and numerous whitish-yellow foci. Organs and tis-
sues were anemic.
1. What is your diagnosis?
2. What is the type (stage) of the disease according to revealed histological
changes in lymph nodes?
3. What cells are diagnostic?
4. What is the name of the spleen described above?
5. A 45-year-old woman had 20 000 leukocytes in 1 l of blood; 40% of them were

blasts. Moreover she had decreased level of red blood cells (anemia) and thrombo-
cytes (thrombocytopenia). Liver and spleen were markedly enlarged.
On microscopical examination of trephine biopsy, numerous blasts (tumor cells) in-
filtrating the bone marrow were revealed.
Treatment resulted in remission, the patient was discharged home.
1. What is the most likely type of leukemia in this case?
2. What is the pathogenesis of anemia and thrombocytopenia?
3. What is the cause of liver and spleen enlargement?
4. What differential diagnostic value has cytochemical markers examination?
5. What prognosis has this type of leukemia for grown-ups?
ANSWERS
1 2 3 4 5
1 Acute lym- Leukemic infil- Enlargement of or-
phoblastic trates destroy gans occurs due to
leukemia vascular walls, infiltration and prolif-
thrombocytopenia eration of leukemic
cells in them
2 Chronic mye- Blastic crisis in- Leukemic infiltrates
loid leuke- dicates the trans- with proliferation of
mia, chronic formation of the tumor cells
(monoclonal) benign monoclo-
phase nal phase of
chronic myeloid
leukemia to ma-
lignant polyclonal
phase
3 Multiple my- In flat bones Damage of bone by Paraproteins Depositions of
eloma; plas- tumor cellular infil- (pathologic paraproteins, amy-
ma cell dis- trate with following immuno- loidosis
orders focal resorption of globulins)
(paraproteina bone
emias)
4 Lymphogran Mixed-cellularity Reed-Berezovski- Porphyry
ulomatosis or type Sternberg cells, small spleen
Hodgkin's and large Hodgkins
disease cells
5 Acute mye- As the leukemic Leukemic infiltrates Cytochemical Relatively favora-
loid leukemia cells accumulate with proliferation of markers defi- ble prognosis.
in the bone mar- tumor cells nitely show a Remissions occurs
row, there is sup- type of leu- in 70-80% of pa-
pression of nor- kemia, that tients, the 25% of
mal hematopoiet- has a great latter has com-
ic stem cells, in value for plete remission
particular target treat-
erythroid and ment
megakaryocyte
series
5. Self assessment.
1. The diagnostic cell for Hodgkin's disease is:
1. Lymphocyte
2. Foam cell
3. Reed-Sternberg cell
4. Myeloma cell
5. Macrophage
2. The following type of reactive lymphadenitis in the draining lymph nodes of some can-
cers renders better prognosis due to good host immune response:
1. Follicular hyperplasia
2. Sinus histiocytosis
3. Paracortical hyperplasia
4. Immunoblastic lymphadenopathy
5. None of the above
3. M-band is seen in multiple myeloma on electrophoresis in the region of:
1. Alpha-1 (1) globulin
2. Alpha-2 (2) globulin
3. Beta () globulin
4. Gamma () globulin
5. All of the above
4. Intermediate grade lymphomas include all of the following variants, EXCEPT:
1. Follicular, predominantly large-cell lymphoma
2. Follicular, predominantly small cleaved cell lymphoma
3. Diffuse, small cleaved cell lymphoma
4. Diffuse, mixed small-and large-cell lymphoma
5. Diffuse large-cell lymphoma
5. Myeloproliferative disorders include the following, EXCEPT:
1. Acute myeloid leukemia
2. Chronic myeloid leukemia
3. Polycythemia vera
4. Agnogenic myeloid metaplasia
5. Essential thrombocytosis
6. The diagnostic cell for multiple myeloma is:
1. T lymphocyte
2. Eosinophile
3. Reed-Sternberg cell
4. Plasma cell
5. lymphocyte
7. Reed-Sternberg cells are generally believed to be of:
1. T cell origin
2. Endothelial cells
3. Follicular reticulum cells
4. Macrophages
5. cell origin
8. Acute splenic tumor means:
1. Rapidly developing primary splenic lymphoma
2. Rapidly developing primary splenic carcinoma
3. Rapidly developing metastatic carcinoma
4. Splenic enlargement due to infiltration by leukemia
5. Splenic enlargement due to systemic acute infection
9. Chronic myelogenous leukemia is characterized by all of the following features,
EXCEPT:
1. Lack of alkaline phosphatase in circulating neutrophils
2. Splenomegaly
3. Transition to acute leukemia
4. Philadelphia chromosomes in stem cells
5. Excellent response to chemotherapy
10. Reed-Sternberg cells of all types of Hodgkin's disease are positive for CD15 and CD30
markers, except:
1. Lymphocyte predominance
2. Nodular sclerosis
3. Mixed cellularity
4. Lymphocyte-depletion (diffuse fibrotic variant)
5. Lymphocyte-depletion (reticular variant)
11. Multiple myeloma is characterized by abnormal accumulation of what substances in
tissues?
1. Hyaline
2. Lipofuscin
3. Amyloid
4. Hemosiderin
5. Melanin
12. Lacunar type of Reed-Sternberg cells is a feature of which of the following types of
Hodgkin's disease:
1. Lymphocyte-predominance
4. Lymphocyte-depletion
5. All of the above
13. Leucocyte alkaline phosphatase (LAP) scores are elevated in:
1. Acute myeloid leukemia
2. Chronic myeloid leukemia
3. Myeloid metaplasia
4. Myeloid leukemoid reaction
5. All of the above
14. Subtypes of Hodgkin's disease include all of the following, EXCEPT:
3. Lymphocyte predominance
4. Nodular amyloidosis
5. Lymphocyte depletion
15. The following classification systems have been used for classifying non-Hodgkin's lymphoma,
except:
1. Rappaport classification
2. Rye classification
3. Working formulation
4. R.E.A.L. classification
5. Lukes-Collins classification
16. Burkitt lymphoma is characterized by:
1. Starry sky appearance
2. Infiltration of plasma cells
3. Presence of foam cells
4. Presence of Reed-Sternberg cells
5. Glassy appearance of the cell
17. The following type of non-Hodgkin's lymphoma more commonly produces chronic lympho-
cytic leukemia-like picture after spill over into peripheral blood:
1. Follicular, predominantly large cell lymphoma
2. Follicular, small cleaved cell lymphoma
3. Follicular, mixed small and large cleaved cell lymphoma
4. Small lymphocytic lymphoma
5. None of the above
18. All of the following statements correctly describe nodular non-Hodgkin's lymphomas,
EXCEPT:
1. They are often associated with a predictable chromosomal translocation
2. They have a better prognosis than diffuse lymphomas
3. They are characterized by cells with irregular nuclear contours
4. They are always composed of neoplastic cells
5. They are highly responsive to chemotherapy
19. Splenomegaly is common in terminal stages of all the following diseases, except:
1. Chronic lymphocytic leukemia
2. Chronic myelogenous leukemia
3. Spherocytosis
4. Sickle cell anemia
5. Hodgkin's disease, stage IV
20. Langerhans' cell histiocytosis includes the following entities, except:
1. Eosinophilic granuloma
2. Hand-Schller-Christian disease
3. Histiocytic lymphoma
4. Letterer-Siwe disease
5. Histiocytosis X
ANSWERS
1 3 11 3
2 2 12 2
3 4 13 4
4 2 14 4
5 1 15 2
6 1 16 1
7 4 17 4
8 5 18 5
9 4 19 4
10 3 20 3

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PRACTICAL GUIDE

For 3rd year students of medical faculty

O.V. Lesnichaya, I.V. Samsonova

1. Study the questions:

I. Study the macropreparations:

II. Study the micropreparations:

III. Complete the tables:

Structural changes of organs in protein and fatty parenchymatous dystrophies

Parenchymatous protein dystrophies

2. A patient had glomerulonephritis with nephrotic syndrome. 20 g of protein was

5. A woman appealed to a physician for medical aid. She complained of weakness,

MESENCHYMAL FATTY DEGENERATIONS

I. Study the macropreparations:

II. Study the micropreparations:

27-. Atherosclerosis of artery. (st. hematoxylin and eosin). Using small

III. Complete the tables:

Description of stages of connective tissue desorganization

3. A patient suffered from hypertensive vascular disease and died of myocardium

1. Study the questions:

I. Study the macropreparations:

II. Study the micropreparations:

32 Liver in mechanical jaundice. (st. hematoxylin and eosin). Find dilat-

7 Brown atrophy of the myocardium. (st. hematoxylin and eosin). Study

29 Necrosis of the skeletal muscle with ossification. (st. hematoxylin

36 Hemosiderosis of spleen. (Perls stain). Find accumulations of blue

III. Complete the tables:

Classification of haemoglobinogenic pigments.

Name of pigment Physiologic Pathologic Iron-containing pig- Iron-free

Form of Causes Localization of Outcomes

6. A woman suffering from cholelithiasis presents to the emergency department

1. Study the questions:

2. Fill in the table:

3. The theoretical part.

DEATH, SIGNS OF DEATH, POSTMORTEM CHANGES

II. Study the micropreparations:

2 Necrotic nephrosis (necrosis of kidney epithelium). (st. hematoxylin

III. Complete the tables:

Clinical-morphological forms of necrosis

1. A 67-year-old woman suffering from mesenterial arteries atherosclerosis for a

4 Infarction Thromboembolism from the Pale with hemor- In kidneys: organization

1. Study the questions:

II. Study the micropreparations:

44 Cyanotic induration of spleen. (st. hematoxylin and eosin). Pay atten-

III. Complete the table (see theoretical part).

Kinds of blood supply disturbances

Chronic general venous (chronic cardiovascular insufficiency) congestion

4. On postmortem examination of a patient with atherosclerosis, almost total occlu-

1. Study the questions:

TABLE 1 DISTINGUISHING FEATURES OF ARTERIAL AND VENOUS

TABLE 2 ANTEMORTEM THROMBI VERSUS POSTMORTEM CLOTS

I. Study the macropreparations:

39 Haemorrhagic infarct of the lung. (hematoxylin and eosin staining).

III. Fill in the tables:

Blood clots classification

1. Study the questions:

I. Study the macropreparations:

55- Lobar pneumonia (the stage of grey hepatization). (hematoxylin

65 Catarrhal gastritis. (hematoxylin and eosin staining). Study. Mucous

III. Complete the tables:

Sequence of inflammatory phases

1. A 53-year-old man suffered from chronic glomerulonephritis for 15 years, died of

2. A 5-year-old child died of meningococcal meningitis. At autopsy, the gyri and

I. Study the questions:

Main classifications of chronic inflammation