ORENBURG STATE MEDICAL UNIVERSITY
DEPARTMENT OF PATHOLOGICAL ANATOMY
METHODICAL MANUAL FOR PRACTICAL TRAINING FOR STUDENTS OF
FOREIGN FACULTY
THEME:
DISEASES OF FEMALE GENITAL ORGANS. DISEASES OF UTERUS. PRENEOPLASTIC
DISEASES AND TUMORS OF THE CERVIX AND UTERUS. DISEASES OF OVARIES,
FALLOPIAN TUBES AND MAMMARY GLAND.
I. Diseases of the cervix: cervicitis, endocervical polyps, endocervicoses, cervical
cancer.
1. CERVICITIS - inflammation of the cervix, can be acute or chronic, it causes
numerous bacteria, viruses and fungi. It is characterized by a combination of
inflammatory infiltration, degeneration of the epithelium, its necrosis and
desquamation with the formation erosion. At the true cervical erosion usually
epithelialization is quickly occurs.
2. Endocervicoses (pseudoerosion, ectropion). Vaginal portion of the cervix
normally covered by stratified squamous epithelium neorogovevayuschy when
pathology is replaced by a cylindrical.
3. Cervical cancer. There are non-invasive (cervical intraepithelial neoplasia) and
invasive cancer. Precancerous changes - dysplasia, metaplasia, leukoplakia,
endocervicoses. Histological type - squamous cell carcinoma and adenocarcinoma.
4. Glandular (adenomatous) polyps endocervical - a benign tumor, can be
malignant.
II. Diseases of the uterine body: dysfunctional uterine bleeding, inflammation,
adenomyosis, endometriosis, endometrial hyperplasia, tumors of the uterine body.
1. Dysfunctional uterine bleeding. Since puberty and before menopause the
endometrium undergoes cyclic changes caused by cyclic changes in the level
of hormones of the pituitary gland and the ovaries. Changes in the level of
estrogen and progesterone is accompanied by violation of the cyclic
maturation of the endometrium, which manifests dysfunctional uterine
bleeding. Reasons: anovulatory cycle, failure of the corpus luteum,
endometrial hyperplasia.
2. Endometrium : a) Acute endometritis caused by ingestion of pathogens into
the uterus in the postpartum period, after surgery and abortions.
Inflammation is exudative character with leukocyte infiltration. b) Chronic
inflammation of the uterus occurs as metroendometritis as the outcome of
acute endometritis or - without acute stage as chronic inflammation. The
process involves the entire endometrium, including the basal layer, the
proliferative change prevail over exudative processes.
3. Adenomyosis of myometrium - glands of the endometrium with the
surrounding cytogenetic stroma, deeply in the myometrium, remote from the
basal layer of 2-3mm. Wall of the uterus is thickened and on the cut the
granular form with small cysts and hemorrhages. Provocative moments -
diagnostic curettage, abortion, manual examination of the uterus after
childbirth.
4. Ectopic endometriosis is most often found in the ovaries (to 70% of cases).
Endometrial cysts in the ovaries may be greater than 10 cm in diameter,
have a hemorrhagic contents, the inner surface of brown ('chocolate' cysts).
The second most frequent localization of external endometriosis believe
peritoneum in the sacro-uterine ligaments, sacro-uterine and recto-uterine
pouch. Less frequent are observed bowel endometriosis (a thin, sigmoid
colon, appendix), urinary tract, lungs, navel, scars after laparotomy.
5. Endometrial hyperplasia is associated with increased and long-existing
high levels of estrogenic stimulation in the reduced or absent activity of
progestins. Characterized by varying the size and shape of glands, increasing
their numbers, some cystic glands expand. The epithelium of the glands
proliferative type by increasing their number in some glands lining has a
multi-row, multi-layered character. The stroma lymphohistiocytic infiltrate.
Tumors of the uterine body: endometrial polyp, endometrial cancer, leiomyoma.
1. Endometrial polyps is often formed during perimenopause, may developed in
the reproductive age, postmenopausal women. Polyps are formed from the basal
layer of the endometrium and are characterized by benign monoclonal proliferation
of mesenchyme. There are single and multiple, their sizes range from microscopic
to large. In rare cases, the polyps may occupy the entire cavity of the uterus. The
surface of the polyps yellowish-brown, shiny, smooth, sometimes with ulcerations.
2. Leyomioma is benign tumor of the smooth muscle. This tumor are observed in
15-30% of women older than 35 years. At the age of 18 myoma is rare, in
postmenopausal tumor regresses. There was a relationship of her diseases and state
accompanied by excess estrogen, which are considered the main growth stimulant
of myoma nodes.
3. Cancer of the endometrium. Incidence of pre-menopausal women increases
when there are anovulatory cycles (follicular development is not completed
ovulation), therefore, does not form the corpus luteum producing progesterone.
The most frequent (85%) histological forms of endometrial cancer adenocarcinoma, which can be highly, moderately and low differentiated.
Metastases initially is lymphatic, hematogenous and then implant.
III. Inflammatory diseases of the fallopian tubes.
Salpingitis is caused by various flora. Normally the spread of pathogens occurs by
ascending from the uterus, much less hematogenous and lymphogenous. Allocated
acute and chronic salpingitis.
IV. The main types of ovarian disease include:
1. The non-neoplastic cyst (tumor-like diseases) - follicular cysts, corpus luteum
cysts, polycystic ovaries.
2. Inflammation: oophoritis is relatively rare and is almost always combined with
inflammation of the fallopian tubes (salpingoophoritis).
3. Ovarian tumors are developed from these tissue components: a) the surface
epithelium (serous, mucinous; endometrioid: benign - cystadenofibroma, malignant
- cancer);
b) germ cell tumors (germ cells) - mature teratoma - dermoid cysts; struma and
ovarian carcinoid; dysgerminoma;
c) sex cord stromal tumors (tecoma and fibroma).
Also, there are metastatic lesions from tumors of the uterus, fallopian tubes, ovary
opposite, rarely, breast cancer, gastrointestinal tract, biliary tract, and pancreas. A
classic example is Krukenberg tumor - metastasis of gastric cancer in the ovaries.
V. Mammary gland diseases are divided into inflammatory necrotic, fibrocystic
and tumor.
1. Inflammatory necrotic:
1. Acute mastitis is developing in the postpartum period, aided by stasis of the
milk in the extended ducts and cracked nipples, often occurs in lactating women.
After cracks penetrate the bacteria in the ducts of the breast. Develops purulent
inflammation, with formation of one or more abscess.
2. Ectasia of the ducts a mammary gland - in the extended ducts accumulate secret
and desquamated epithelium, which is accompanied by signs of chronic
inflammation (retention mastitis).
3. Fat necrosis is formed after an injury.
2. Fibrocystic breast changes:
- Cysts and fibrosis,
- Epithelial hyperplasia,
- Sclerosing adenosis,
- Dyshormonal breast.
Common in women 30-45 years old, it is one of the most common injuries. The
risk of malignancy depends on the degree of dysplasia.
3.Breast tumors:
1. Benign epithelial (fibroadenoma, leaf-formed tumor, intraductal papilloma).
2. Malignant epithelial (cancer). A non-invasive cancer (cancer in situ) intraduct or
intralobular so-called carcinoma in situ, without sprouts basal membrane. At
various ratios of the parenchyma and stroma are distinguished: scirrhous,
medullary, colloid. There are three types of cancer: nodular, diffuse, cancer of the
nipple (Paget's disease).
CONTROL QUESTIONS
1.
2.
3.
4.
Diseases of the cervix. Acute and chronic cervicitis. Endocervical
polyps. Epidemiology, etiology, risk factors, morphogenesis,
morphological characteristics, clinical manifestations, outcomes.
Cervical cancer. Epidemiology, risk factors, diagnostic methods,
precancerous conditions. Cervical intraepithelial neoplasia and invasive
cervical cancer. Classification, morphological characteristics, clinical
manifestations, prognosis.
Diseases of the body uterus and endometrium. Classification:
inflammatory, dyshormonal and neoplastic. Risk factors.
a) acute and chronic endometritis. Morphological characteristics and
clinical manifestations.
b) Adenomyosis. Endometriosis. Morphological characteristics,
theories, clinical manifestations and clinical significance.
c) Glandular endometrial hyperplasia. The classification, causes,
morphological characteristics, the prognosis (risk of malignancy).
d) tumors of the uterus body. Classification. Benign tumors of the
epithelium. Endometrial polyps. Clinical and morphological
characteristics.
Cancer of the endometrium. Epidemiology, predisposing factors,
classification. Macroscopic characteristics, histological forms, regularity
of metastasis, prognosis.
5.
6.
7.
8.
Mixed and mesenchymal tumors. Fibromioma. Morphological
characteristics, classification. Leiomyosarcoma. Malignant mixed
mesodermal tumors. Endometrial stromal tumors. Clinical and
morphological characteristics, prognosis.
Tumors of the of ovaries. Risk factors. Classification. Features
histogenesis. Benign and malignant tumors of the superficial epitheliaum,
the genital and germ cells, ovarian stroma. Ovarian cancer:
morphological characteristics, prognosis. Metastatic lesions of the
ovaries (Krukenberg tumor).
Fibrocystic changes mammary glands. Breast tumors. Classification.
Benign tumors. Fibroadenoma. Leaf-shaped tumor. Intraductal
papilloma. Morphological characteristics, clinical significance.
Mammary cancer. Epidemiology, risk factors and pathological
morphogenesis, morphological types and morphological characteristics,
clinical manifestations. Stage distribution by TNM. Prognosis and longterm outcomes.
The practical part of the subject:
Slides: In the study micropreparations pay attention to the education
elements, designated by the letters in parentheses.
1.
2.
3.
4.
Glandular hyperplasia endometrium. H & E stain. In the endometrium
amounts of iron is increased, they have different size and configuration (a),
the epithelium of proliferative type, multirowed, sometimes epithelium
formed to papillary outgrowths into the lumen of the glands (b), in the
stroma histiocytic and lymphocytic infiltrates (c).
Fibroadenoma of the breast. H & E stain. Glands ducts extended and lined
by multilayer multirowed epithelium (a), are observed the glandular tumor
formation (b), surrounded by connective tissue (c).
Acute septic endometritis. H & E stain. In the endometrium are observed
epithelial desquamation (a), areas of necrosis (b), the deposition of fibrin (c),
leukocyte infiltration (d). The myometrium is infiltrated leukocytes (e), vein
is obturated by thrombi (f).
Endocervicoses (cervical ectopia of the cervix). H & E stain. In the
mucosa of the exocervix are observed papillary growths of high prismatic
epithelium (a), subiculum with glandular structures (b) and thin-walled
blood vessels (c). Transition boundary stratified squamous epithelium in a
prismatic epithelium (g) are observed.
5.
6.
7.
Adenocarcinoma of the endometrium. H & E stain.
In the endometrium are determined atypical endometrial glandular
complexes of different sizes and shapes (a), constructed of polymorphic
cells endometrioid type (b), epithelium is multirowed, its polarity is
broken (c), the nucleus is large, hyperchromatic, with the presence of mitosis
(d).
Squamous cell carcinoma of the cervix. H & E stain.
In the cervical tissue are determined a solid structure, built of polymorphic
polygonal cells with large hyperchromatic nuclei (a). In the tumor tissue are
visible necrosis (b) and inflammatory foci (c).
Scirrhous breast cancer. H & E stain.
a- strands of tumor cells, b - the stroma
Macropreparations:
1.Cancer of the endometrium.
In preparation of the uterus with appendages, uterus is increased to the size of a 16week pregnancy. In the bottom are visible tumor site, exophytic growing into the
cavity, irregular and rounded form, motley appearance, soft texture, 2 cm in
diameter. On the cut tumor invades the uterine wall.
The reasons: infringement of hormonal background, the influence of carcinogenic
factors.
Complications and outcomes: sprouting in adjacent organs, metastasis to the
lymph nodes.
2.Cervical cancer.
In preparation of the uterus with appendages, normal size, the cervix is deformed
in a "cauliflower".
Reason: infringement of hormonal background, the influence of carcinogenic
factors, chronic cervicitis with metaplasia and dysplasia.
Complications and outcomes: sprouting the bladder, colon, metastasis to the
lymph nodes.
3.Mammary cancer.
In preparation of the mammary gland, on the cut is determined by the tumor site
dense gray with indistinct borders sprouting surrounding tissue.
Reason: infringement of hormonal background, the influence of carcinogenic
factors.
Complications and outcomes: metastasis to regional lymph nodes, later
hematogenous metastases.
4.Serous ovarian cyst.
In preparation of the ovary, it increased in size due to the thin-walled cavity
formation, spherical shape, measuring 5 cm filled with a clear liquid. In a cut the
internal cyst smooth. Ovarian parenchyma atrophy.
Reason: infringement of hormonal background.
Outcomes: the gap with the development peritonitis, hemoperitoneum.
Test control
Select one or more correct answers
1.TERM INTERNAL "adenomyosis" means
1) heterotopic pancreatic tissue site, located in the muscular layer of the
gastrointestinal tract
2) tissue complexes consisting of glandular and stromal elements in the
myometrium without signs of tumor growth
3) the growth of ectopic endometrial elements
2. Physiological proliferative changes in the endometrium
1) cystic expansion of the lumen with hyperplasia of glandular epithelium
2) the presence of tubular glandular crypts with high dark cell epithelium
3) the presence of sawtooth glandular crypts with a flattened cuboidal epithelium
4) rejection of menstrual endometrium
5) basal cell hyperactivity
3. LAYERS endometrial a mature woman
1) Functional
2) intermediate
3) basal
4. PHASE ovarian-menstrual cycle in childbearing years
1) follicular
2) progestin
3) secretory
4) luteal
5. Diffuse desquamation glandular epithelium with hemorrhagic infiltration of the
stroma observed at
1) ovulatory endometrium hyperemia
2) acute viral endometritis
3) Botkin's disease
4) rejection of menstrual endometrium
5) all of the above is true
6. CHARACTERISTICS OF CERVICAL leukoplakia
1) violation of the maturation of the epithelium with a predominance of immature
cell forms
2) an increase in the differentiation of cellular elements with a tendency to
keratinization squamous epithelium cells
3) the appearance of glandular structures in the ectocervix
4) papillomatous proliferation of the squamous epithelium
7.The characteristics of the true cervical erosion
1) an increase in the differentiation of cellular elements with a tendency to
keratinization squamous epithelium
2) destruction of the epithelium with inflammatory infiltration
of the underlying tissue
3) The proliferation of backup squamous cells
4) retention cysts of the cervix
8. Histological features of atypical endometrial hyperplasia
1) severe atrophy glands in combination with increased proliferative activity of the
epithelium part of the gland
2) marked proliferation of glands with a change in their pattern ("gland in
gland") and the appearance of papillary structures
3) in some epithelial cells are observed tumor polymorphism
4) the predominance of stromal component
9. The more common ovarian tumors
1) Benign
2) malignant
10. Epithelial ovarian tumors
1) serous
2) mucinous
3) endometrioid
4) fibroma
5) Brenner tumor
11. Stomach cancer metastases in the ovary
1) Brenner tumor
2) tumor Krukenberg
3) tumor Paget
4) Leydig tumor
12. FREQUENTLY histological forms of cancer endometrial
1) squamous cell carcinoma
2) adenocarcinoma
3) scirrhoma (fibrous)
13. The basic theory of endometriosis
1) The theory of regurgitation
2) the theory of metaplasia
3) The theory of hematogenous and lymphatic spread
4) the anomaly of the uterus
14. Cyst at the endometriosis
1) follicular
2) luteinized
3) "chocolate"
4) common
5) serous
15. Benign tumors of the corpus uteri
1) fibroma
2) papilloma
3) chondroma
4) ganglioma
16. Endometrial cancer T4, ACCORDING TNM system
1) carcinoma in situ
2) the tumor is within the uterus
3) sprouting to the wall of the bladder, rectum
4) the tumor grows into the myometrium
17. The most common tubal pathology
1) salpingitis
2) Brush
3) tumor
4) malformations
18. Benign breast disease
1) fibroadenoma
2) leaf-formed tumor
3) intraductal papilloma
4) carcinoma «in situ"
19. SELECT invasive forms of breast cancer:
1) intraduct cancer
2) lobular carcinoma in situ
3) medullary cancer
4) mucinous carcinoma
5) tubular cancer
20. What is Paget's disease:
1) superficial cancer of the nipple and areola of the breast
2) lobular carcinoma in situ
3) medullary cancer
4) mucinous carcinoma
ORENBURG STATE MEDICAL UNIVERSITY
DEPARTMENT OF PATHOLOGICAL ANATOMY
METHODICAL MANUAL FOR PRACTICAL TRAINING FOR STUDENTS OF
FOREIGN FACULTY
THEME:
PATHOLOGY OF PREGNANCY, POSTPARTUM AND PLACENTA.
PRE- AND POSTNATAL DISORDERS. CONGENITAL DEFECTS
Disorders of Pregnancy. GESTATIONAL AND PLACENTAL DISORDERS
SPONTANEOUS ABORTION
Spontaneous abortion, or “miscarriage,” is defined as pregnancy loss before 20
weeks of gestation. Most of these occur before 12 weeks. Ten to fifteen percent of
clinically recognized pregnancies terminate in spontaneous abortion. However,
using sensitive chorionic gonadotropin assays, it has been identified that an
additional 22% of early pregnancies in otherwise healthy women terminate
spontaneously. The causes of spontaneous abortion are both fetal and maternal.
Chromosomal anomalies such as aneuploidy, polyploidy, and translocations are
present in approximately 50% of early abortuses. More subtle genetic defects, for
which routine genetic testing is not readily available, account for an additional
fraction of abortions. Maternal factors include luteal-phase defect, poorly
controlled diabetes, and other uncorrected endocrine disorders. Physical defects of
the uterus, such as submucosal leiomyomas, uterine polyps, or uterine
malformations may prevent implantation adequate to support fetal development.
Systemic disorders affecting maternal vasculature, such as antiphospholipid
antibody syndrome, coagulopathies, and hypertension, may predispose to
miscarriage.
ECTOPIC PREGNANCY
Ectopic pregnancy is the term applied to implantation of the fetus in any site other
than a normal intrauterine location. The most common site is within the fallopian
tubes (∼90%). Other sites include the ovary, the abdominal cavity, and the
intrauterine portion of the fallopian tube (cornual pregnancy). Ectopic pregnancies
occur about once in every 150 pregnancies. The most important predisposing
condition, present in 35% to 50% of patients, is prior pelvic inflammatory disease
resulting in fallopian tube scarring (chronic follicular salpingitis).
Morphology. Tubal pregnancy is the most common cause of hematosalpinx
(blood-filled fallopian tube) and should always be suspected when a tubal
hematoma is present. Initially the embryonal sac, surrounded by placental tissue
composed of immature chorionic villi, implants in the lumen of the fallopian tube.
With time trophoblastic cells and chorionic villi start to invade the fallopian tube
wall as they do in the uterus during normal pregnancy. However, proper
decidualization is lacking in the fallopian tube, and growth of the gestational sac
distends the fallopian tube causing thinning and rupture. Fallopian tube rupture
frequently results in massive intraperitoneal hemorrhage. Less commonly the tubal
pregnancy may undergo spontaneous regression and resorption of the entire
conceptus. Still less commonly, the tubal pregnancy is extruded through the
fimbriated end into the abdominal cavity (tubal abortion).
Gestosis (toxicosis of pregnancy) is the most common pathology is directly linked
to pregnancy. Early gestosis include vomiting of pregnancy, excessive vomiting
and ptyalism. There are 1-3 months pregnant and due to overstimulation of the
autonomic nervous impulses from the center of the uterus and increased inhibition
of the cerebral cortex, increasing the concentration of estrogen and progesterone in
a woman's blood. Excessive vomiting, to 20 times a day, leading to a sharp
exhaustion and dehydration, vitamin deficiency. In very severe cases can develop
gipohloremichesky coma.
The forms of late gestosis: edema, nephropathy, preeclampsia and eclampsia. Late
developing preeclampsia, since 32-34ned pregnancy. Most preeclampsia observed
in multiple pregnancies. Early development and heavy for preeclampsia noted at
hydatidiform moles. The main link in the pathogenesis of preeclampsia is a
violation of trophoblast invasion and the resulting pathology of the spiral arteries
of the uterus.
Morphology. The placenta reveals various microscopic changes, most of which
reflect malperfusion, ischemia, and vascular injury. These include: (1) Placental
infarcts—small, peripheral ones that may occur in normal full-term placentas—are
larger and more numerous in preeclampsia. There is also an exaggeration of
ischemic changes in the chorionic villi and trophoblast. This includes increased
syncytial knots and the appearance of accelerated villous maturity. (2) There is
increased frequency of retroplacental hematomas due to bleeding and instability of
uteroplacental vessels. (3) The most characteristic finding is in the decidual
vessels, reflecting abnormal implantation. This can be in the form of thrombosis,
lack of normal physiologic conversion (described earlier), fibrinoid necrosis, or
intraintimal lipid deposition (acute atherosis). The liver lesions, when present, take
the form of irregular, focal, subcapsular, and intraparenchymal hemorrhages. On
histologic examination there are fibrin thrombi in the portal capillaries and foci of
hemorrhagic necrosis.The kidney lesions are variable. Glomerular lesions are
diffuse, when assessed by electron microscopy. They consist of marked swelling of
endothelial cells, the deposition of fibrinogen-derived amorphous dense deposits
on the endothelial side of the basement membrane, and mesangial cell hyperplasia.
Immunofluorescent studies show an abundance of fibrin in glomeruli. In the better
defined cases, fibrin thrombi are present in the glomeruli and capillaries of the
cortex. When the lesion is far advanced, it may produce complete destruction of
the cortex in the pattern referred to as bilateral renal cortical necrosis. The brain
may have gross or microscopic foci of hemorrhage along with small-vessel
thromboses. Similar changes are often found in the heart and the anterior
pituitary.
Pathology of the placenta
During pregnancy, the link between the mother's body and fetus through the
placenta. Through it, the parent body of a fetus receives oxygen, glucose, amino
acids, electrolytes, hormones, and other substances from the body of the fetus and
the mother's blood to carbon dioxide and other metabolites. The placenta has the
ability to synthesize hormones and protects the unborn child from infection.
Human placenta has gemohorialny type of structure. Normally, the blood of the
fetus and mother are not mixed.
ABNORMALITIES OF PLACENTAL IMPLANTATION
Abnormal placental implantations may have significant consequences for the
pregnancy outcome. Placenta previa is a condition in which the placenta implants
in the lower uterine segment or cervix, often with serious third-trimester bleeding.
A complete placenta previa covers the internal cervical os and thus requires
delivery via cesarean section to avert placental rupture and fatal maternal
hemorrhage during vaginal delivery. Placenta accreta is caused by partial or
complete absence of the decidua with adherence of the placental villous tissue
directly to the myometrium and failure of placental separation. It is an important
cause of postpartum bleeding, which often may be life-threatening to the mother.
Common predisposing factors are placenta previa (in up to 60% of cases) and
history of previous cesarean section.
TWIN PLACENTAS
Twin pregnancies arise from fertilization of two ova (dizygotic) or from division of
one fertilized ovum (monozygotic). There are three basic types of twin placentas (
Fig. 22-53 ): diamnionic dichorionic (which may be fused), diamnionic
monochorionic, and monoamnionic monochorionic. Monochorionic placentas
imply monozygotic (identical) twins, and the time at which splitting occurs
determines whether one or two amnions are present. Dichorionic placentation may
occur with either monozygotic or dizygotic twins and is not specific.
One complication of monochorionic twin pregnancy is twin-twin transfusion
syndrome. In all monochorionic twin placentas there are vascular anastomoses,
which connect the circulations of the twins. In some cases there is an abnormal
sharing of fetal circulations through an arteriovenous shunt. If an imbalance in
blood flow occurs, a marked disparity in fetal blood volumes may result in twintwin transfusion syndrome and the death of one or both fetuses.
PLACENTAL INFECTIONS
Infections in the placenta develop by two pathways: (1) ascending infection
through the birth canal and (2) hematogenous (transplacental) infection. Ascending
infections are by far the most common and are virtually always bacterial; in many
such instances, localized infection of the membranes by an organism produces
premature rupture of membranes and preterm delivery. The amniotic fluid may be
cloudy with purulent exudate, and histologically the chorion-amnion contains a
polymorphonuclear leukocytic infiltrate accompanied by edema and congestion of
the vessels. The infection frequently elicits a fetal response with “vasculitis” of
umbilical and fetal chorionic plate vessels. Uncommonly, bacterial infections may
arise by the hematogenous spread of bacteria directly to the placenta. The villi will
then show acute inflammatory cells (acute villitis).
circulatory disorders. Types of disorders of blood circulation in the placenta is
very diverse; their clinical significance is ambiguous - some lead to significant
suffering of the fetus, while others are asymptomatic. The most frequent and
important are infarction, hematoma, thrombosis, fibrinoid.
Infarct
Fresh infarct triangular or irregular shape. It is dense, dark red, with clear
boundaries. Older infarcts - yellow or white, sometimes with cysts. Histologically
intervillous space narrowed sharply, nap close together, they slept in the vessels,
stroma and epithelium exposed dystrophic and necrotic changes. In the old heart
attacks are only the "shadow" of the villi. Around the infarct zone is sometimes
formed infiltration of polymorphonuclear leukocytes. The cause infarction - the
absence of blood flow in the intervillous space of the mother, often spiral artery
thrombosis.
retroplacental hematoma
Retroplacental hematoma located on the back surface and compresses the
parenchyma. Retroplacental hematoma is often, but not always, accompanied by
clinical signs of placental abruption. The development of a hematoma associated
with the rupture of the arterioles decidua and / or violation of the venous outflow.
Like other types of circulatory disorders, the disorder is accompanied by a decrease
in oxygen supply to the fetus. The clinical significance may be as massive blood
loss in the mother hematomas.
fibrinoid
The deposition of fibrinoid looks like a tight, well-delimited, white and yellow
center with a diameter of a few centimeters, it is often located at the periphery of
the placenta. Histologically determined fibrinod. The villi gradually obliterating
vessels and progressive fibrosis. These changes develop as a result of stopping the
blood flow in the intervillous space of the placenta.
Fetal arterial thrombosis
Fetal arterial thrombosis accompanied by clinical and morphological
manifestations when developing vascular stem villi. In this case, the villi of smaller
caliber, extending from the affected stem nap, developing fibrosis and vascular
obliteration. Grossly the pathological process looks like a triangular white patch in
the parenchyma of placenta. Intervillous space of fetal arterial thrombosis remains
free. The pathogenesis of thrombosis are not entirely clear, one of the alleged
reasons it is a bleeding disorder fetus.
Pathology of the umbilical cord
Short umbilical cord restricts the movement of the fetus. At birth, she can stretch,
which leads to disruption of blood flow in, or placental abruption. The long cord is
often twists, forms the true knots, loops falls during childbirth. These
complications are dangerous to compress the blood vessels of the umbilical cord
and development of fetal hypoxia. Single umbilical artery (umbilical artery aplasia)
is often associated with congenital malformations and fetal malnutrition. Etiology
and pathogenesis of this evil are not clear.
Gestational Trophoblastic Disease
Gestational trophoblastic disease constitutes a spectrum of tumors and tumor-like
conditions characterized by proliferation of placental tissue, either villous or
trophoblastic. The lesions include hydatidiform mole (complete and partial),
invasive mole, and the frankly malignant choriocarcinoma and placental-site
trophoblastic tumor.
HYDATIDIFORM MOLE
Hydatidiform mole is characterized histologically by cystic swelling of the
chorionic villi, accompanied by variable trophoblastic proliferation. The most
important reason for the correct recognition of moles is that they are associated
with an increased risk of persistent trophoblastic disease (invasive mole) or
choriocarcinoma. In the past, most patients presented in the fourth or fifth month of
pregnancy with vaginal bleeding. Currently, hydatidiform moles are being
diagnosed at earlier gestational ages (8.5 versus 17.0 weeks) due to routine
ultrasound and close monitoring of early pregnancy. Molar pregnancy can develop
at any age, but the risk is higher at the far ends of reproductive life: in teens and
between the ages of 40 and 50 years. For poorly explained reasons, the incidence
varies considerably in different regions of the world. Hydatidiform mole is a rather
infrequent complication of gestation in the United States, occurring about once in
every 1000 to 2000 pregnancies, but is quite common in the Far East; the incidence
is 1 in 100 in Indonesia.Two types of benign, noninvasive moles—complete and
partial—can be identified by cytogenetic and histologic studies.
Complete Mole
Complete mole results from fertilization of an egg that has lost its chromosomes,
and the genetic material is completely paternally derived . Ninety percent have a
46,XX diploid pattern, all derived from duplication of the genetic material of one
sperm (a phenomenon called androgenesis). The remaining 10% are from the
fertilization of an empty egg by two sperm (46,XX and 46,XY). Histologically, in
complete mole all or most of the villi are enlarged and edematous, and there is
diffuse trophoblast hyperplasia. Although fetal vessels and fetal parts are extremely
rare in complete moles since the embryo dies very early in development, they do
occur. Patients have 2.5% risk of subsequent choriocarcinoma.
Partial Mole
Partial moles result from fertilization of an egg with two sperm. In these moles the
karyotype is triploid (e.g., 69,XXY) or even occasionally tetraploid (92,XXXY).
Fetal parts are more commonly present than in complete moles. In partial moles
some of the villi are edematous, and other villi show only minor changes; the
trophoblastic proliferation is focal and less marked. Although partial moles have an
increased risk of persistent molar disease, they are not considered to have an
increased risk for choriocarcinoma.
Morphology. The classic gross appearance is of a delicate, friable mass of thinwalled, translucent, cystic, grapelike structures consisting of swollen edematous
(hydropic) villi. Fetal parts are frequently seen in partial moles. On histologic
examination complete moles show abnormalities that involve all or most of the
villous tissue. The chorionic villi are enlarged, scalloped in shape with central
cavitation (cisterns), and lack adequately developed vessels. The most impressive
abnormality is, however, an extensive trophoblast proliferation that involves the
entire circumference of the villi, in addition to “extravillous” islands of trophoblast
proliferation. The implantation site often displays atypia and an exuberant
proliferation of implantation trophoblast. In contrast, partial moles demonstrate
villous enlargement and architectural disturbances in only a proportion of villi. The
trophoblastic proliferation is moderate but still may be circumferential.
Histologic distinction of complete mole from partial molar gestations is important.
In equivocal cases immunostaining for p57, a cell cycle inhibitor, may aid the
diagnosis. The p57KIP2 gene is maternally transcribed but paternally imprinted,
and shows expression in maternal decidual tissue as well as cytotrophoblast and
stromal cells of the villi, when maternal genetic material is present in the
conceptus. In contrast, since both the X chromosomes in complete moles are
derived from the father, there is no expression of p57 protein in the cytotrophoblast
or stromal cells of the villi in complete moles.
INVASIVE MOLE
This is defined as a mole that penetrates or even perforates the uterine wall. There
is invasion of the myometrium by hydropic chorionic villi, accompanied by
proliferation of both cytotrophoblast and syncytiotrophoblast. The tumor is locally
destructive and may invade parametrial tissue and blood vessels. Hydropic villi
may embolize to distant sites, such as lungs and brain, but do not grow in these
organs as true metastases, and even without chemotherapy they eventually regress.
The tumor is manifested clinically by vaginal bleeding and irregular uterine
enlargement. It is always associated with a persistently elevated serum HCG and
varying degrees of luteinization of the ovaries. The tumor responds well to
chemotherapy but may result in uterine rupture and necessitate hysterectomy.
CHORIOCARCINOMA
Gestational choriocarcinoma is a malignant neoplasm of trophoblastic cells derived
from a previously normal or abnormal pregnancy, which can even include
extrauterine ectopic pregnancy. Choriocarcinoma is rapidly invasive and
metastasizes widely, but once identified responds well to chemotherapy.
Morphology. Choriocarcinoma is classically a soft, fleshy, yellow-white tumor
with a marked tendency to form large pale areas of ischemic necrosis, foci of cystic
softening, and extensive hemorrhage. Histologically, it does not produce chorionic
villi and consists entirely of a mixed proliferation of syncytiotrophoblasts and
cytotrophoblasts. Mitoses are abundant and sometimes abnormal. The tumor
invades the underlying myometrium, frequently penetrates blood vessels and
lymphatics, and in some cases extends out onto the uterine serosa and into adjacent
structures. Due to rapid growth it is subject to hemorrhage, ischemic necrosis, and
secondary inflammation. In fatal cases metastases are found in the lungs, brain,
bone marrow, liver, and other organs. On occasion, metastatic choriocarcinoma is
discovered without a detectable primary in the uterus (or ovary), presumably
because the primary has undergone complete necrosis.
PLACENTAL - SITE TROPHOBLASTIC TUMOR (PSTT)
PSTTs compose less than 2% of gestational trophoblastic neoplasms and represent
neoplastic proliferation of extravillous trophoblast, also called intermediate
trophoblast. In normal pregnancy, extravillous (intermediate) trophoblast is found
in nonvillous sites such as the implantation site, in islands of cells within the
placental parenchyma, in the chorionic plate, and in the placental membranes. In
contrast, syncytiotrophoblast and cytotrophoblast are present on the chorionic villi.
Normal extravillous trophoblasts are polygonal mononuclear cells that have
abundant cytoplasm and produce human placental lactogen. Malignant
transformation of extravillous trophoblast gives rise to PSTT, which presents as a
uterine mass, accompanied by either abnormal uterine bleeding or amenorrhea and
moderate elevation of β-HCG. Histologically, PSTT is composed of malignant
trophoblastic cells diffusely infiltrating the endomyometrium. PSTTs may be
preceded by a normal pregnancy (one half), spontaneous abortion (one sixth), or
hydatidiform mole (one fifth). Patients with localized disease or a less than 2-year
interval from the prior pregnancy to diagnosis have an excellent prognosis. Tumors
diagnosed at advanced stage, or diagnosed 2 or more years following pregnancy,
have a poor prognosis; overall, about 10% to 15% of women with PSTT die of
disseminated disease
CONTROL QUESTIONS
1. Pathology of pregnancy. Spontaneous abortion. Epidemiology, causes, features
of the morphological study. Ectopic pregnancy. Classification. Reasons
morphological diagnosis, complications and outcomes. Causes of death.
2. Placenta: morpho-functional characteristics. The main types of pathological
processes:
a) infectious processes, ways of infection of the placenta and fetus. Etiology,
morphological manifestations, effects on the fetus and the mother, outcomes.
b) the types of circulatory disorders: fibrinoid deposition. hematoma, infarction,
thrombosis, fetal vessels. Etiology, features of morphogenesis, morphology and
clinical significance.
c) abnormalities of placental disk and placental localization. Classification,
morphological characteristics, clinical significance.
d) placenta of twins: classification, clinical significance. Placental transfusion
syndrome. Pathology of the umbilical cord.
3. Toxemia of pregnancy (gestosis). Classification, Epidemiology. Clinical
manifestations, causes, pathogenesis, morphological characteristics. Effect on the
fetus. The causes of death of women.
4. Trophoblastic disease. Classification. Vesical drift, invasive hydatidiform
mole, chorionepithelioma. Trophoblastic tumor of placental bed. Epidemiology,
morphological characteristics. Clinical manifestations, prognosis.
5. Fetal age and weight of the fetus. Periods of development of the fetus and
newborn.
6. Perinatal pathology. Prematurity and postmaturity. Intrauterine growth
retardation of fetal growth. Causes, clinical and morphological characteristics,
prognosis.
7. Congenital
malformations. Frequency, etiology and pathogenesis.
Classification. Types of teratogens, and features of their impact on the organs of
the fetus. Malformations multifactorial etiology.
8. Diseases and malformations characteristic of individual periods: chromosomal
and genetic diseases.
9. Hemolytic disease of the newborn. Etiology, pathogenesis. Clinical and
morphological forms and manifestations. Prognosis.
10. Mucoviscidosis. Etiology and pathogenesis. Pathologic characteristics of
lesions of the pancreas and other organs. Complications and outcomes.
11. Pneumopathy. The notion of respiratory distress syndrome and its causes.
Classification. Hyaline membrane disease, clinical and morphological
characteristics. Other pneumopathy. Complications and outcomes.
12. Birth trauma: contributing factors and their causes. Birth tumor.
Cephalohematoma. Hemorrhage (epidural, subdural, the adrenal glands in the brain
and spinal cord).
The practical part of the subject:
Slides: In the study micropreparations pay attention to the education
elements, designated by the letters in parentheses.
1. Vesical drift. H & E stain.
Placental villi significantly increased in size with a sharp swelling and
formation of cavities filled with fluid (a), there is a marked proliferation of
syncytiotrophoblast (b).
2. Chorionepithelioma of uterus. H & E stain.
In the tumor tissue there are cells of cytotrophoblast with the absence of true
villi, stroma and vessels (a), are defined polymorphic atypical huge elements of
syncytiotrophoblast (b) and foci of hemorrhage (c).
3. Tubal pregnancy. H & E stain.
In the mucosa of the fallopian tube there is decidua tissue (a), chorionic villi,
which penetrate into the thickness of muscular layer (b), the extravillous
trophoblast cells (c), fibrinoid (d).
4. Abortion in scraping. H & E stain.
Placental tissue is represented by chorionic villi (a) and decidua tissue (b).
5. The pancreas in mucoviscidosis.. H & E stain.
Terminations departments of pancreas and small ducts are dilated (a), in the
lumen of glands and ducts copious amounts of layered secret (b). Glandular
parenchyma is atrophic (c), in storoma there is proliferation of fibrous tissue
(d) with infiltrating lymphocytes, plasmocytes and histiocytes (e).
6. Kernicterus hemolytic disease. Painting on Schmorl.
The brain tissue is determined by acute swelling of neurons with conversion
cells in a "shadow" (a) pronounced proliferation of oligodendroglia (b), the
concentration of indirect bilirubin in neurons (c) and small vessels (d) in glial
cells (e) and myelinated fibers (f).
7. Acute venous hyperemia the lung. H & E stain.
The capillaries and arterioles of the lung expanded and full-blooded (a), in the
lumen of alveolar there is accumulation of edema fluid (b), and a few red blood
cells (c).
8. Bleeding in the brain. H & E stain.
In the brain tissue there is vascular hyperemia (a), diapedetic perivascular
hemorrhage (b) pericellular (c) and perivascular edema (d).
Macropreparations:
1. Tubal pregnancy: In preparation fallopian tube as expanded in ampullar
department up to 1.5 cm, on the cut is determined by fetal egg with a massive
hemorrhage.
Causes: chronic inflammatory diseases of the uterus, the development of
adhesions and narrowing of the lumen of the fallopian tubes. Violation of peristaltic
tube and narrowing of the lumen at the infantilism. Structural pathology tubes and
hypoplasia of the corpus luteum of the ovary. Malformations of the uterus, and
uterine hormonal contraception.
Complications: bleeding, tubal abortion, rupture of the fallopian tubes.
The outcome: abortion in term of 5-6 weeks.
2. Ovarian pregnancy: Ovary dramatically increased in size, there is damage to
the parenchyma in the form of hemorrhage, on the cut in the thickness is
determined by fetal egg. Causes: a structural abnormality of the fallopian tubes.
Complications: internal bleeding, peritonitis. Outcome: ovarian apoplexy.
3. Chorionepithelioma of uterus. The uterus is enlarged, mucous membrane
thickened, in the uterus is determined tumor on a broad basis in the form of juicy
motley cancellous node, sprouting in the myometrium. Causes: pregnancy
complicated vesical drift, after abortion, after ectopic pregnancy, after clinically
normal pregnancy.
4. Vesical drift: The uterus is enlarged in the cavity acinar accumulations
consisting of multiple cystic formations to 1 cm in size, filled with a clear liquid.
The fetus is missing. Reasons: 1) partial vesical drift - predominance fetal
karyotype paternal chromosomes, 2) complete vesical drift - chromosome set of
the sperm is doubled and egg cell nucleus is inactivated or killed. Complications:
bleeding in the I trimester, choriocarcinoma. Outcome: incomplete pregnancy.
5. Hypoplasia of the kidneys. a) For one-sided defeat: the kidney is reduced in
size, its surface is lobed. Reasons: teratogenetic period - up to 8 weeks. It occurs
as an isolated defect and match. It occurs as an isolated defect and combined.
Complications at isolated malformation: growth retardation, renal rickets,
proteinuria, hypertension. The outcome: chronic renal failure.
b) In bilateral lesions: the size and weight of the kidneys is reduced by 1/3, and a
decrease in the number of cups - 5 or less (normal 8-10). Outcome – unfavorable.
6. Anencephaly is absence of the brain, cranial vault bones and soft tissues. The
preparation of premature infants, on the site of the brain is the connective tissue
with cystic cavities and blood vessels. The bones of the skull are absence. The
reasons: the simultaneous action of certain environmental factors, teratogenic
period - up to 8 weeks of fetal development. Accompanied by the adrenal
hypoplasia and aplasia neurohypophysis. Outcome: intrauterine fetal death or in
the first days of life.
7. Craniocerebral hernia - hernial protrusion in the defect of the skull bones.
Reasons: teratogenetichesky period up to 4 months of fetal development
(infections, drugs, metabolic and embryo-fetopathy).
Localization: a) between the frontal bone, b) at the root of the nose, and c)
between the parietal and temporal bone, d) at the junction of the parietal bones and
the occipital bone, etc.) near the inner corner of the eye.
Forms: 1) meningocele - hernial sac presented dura mater and leather, and the
contents of the cerebrospinal fluid. 2) meningoencephalocele - in the hernial sac
sticks out one or another part of the brain. Outcome: large hernia lead to brain
disorders and fetal death.
Test control
Select one or more correct answers
1. The most frequent localization of ectopic pregnancy
1) ovaries
2) the fallopian tubes
3) abdomen
4) the cervix
5) vagina
2. The frequency of spontaneous abortion
1) 5-10%
2) 10-20%
3) 30-40%
4) 40-50%
5) 50%
3. Morphologically eclampsia is characterized
1) systemic fibrinoid necrosis of small vessels
2) disseminated thrombosis of small vessels
3) necrosis and hemorrhage in the organs
4) suppurative metastases
5) vomiting
4. The reasons for late GESTOSIS
1) violation of trophoblast invasion into the myometrium
2) cystic degeneration of placenta
3) The pathology of the uterine spiral arteries
4) calcification of the placenta
5) the allocation of the ischemic placenta tromboplastic substances
5. SIGNS OF INVASIVE vesical drift
1) lung metastases
2) tumor growth
3) transformation of cystic villi
4) the proliferation of trophoblast
5) swollen villi in the vessels of the myometrium
6. SIGNS OF infarction OF THE PLACENTA
1) a sharp narrowing of the intervillous space
2) narrowing of blood vessels in the villi
3) hemorrhagic impregnation of placenta
4) infiltration of polymorphonuclear leukocytes
5) calcification
7. CAUSES PLACENTAL hematoma
1) thrombosis of the spiral arteries
2) infarction
3) placental abruption
4) breaking of spiral arteries
5) breaking of arterioles decidua
8. SIGNS OF THROMBOSIS of fetal ARTERY villi
1) fibrosis and obliteration of small vessels
2) fetal a bleeding disorder
3) bleeding in intervillous space
4) intervillous space free
5) the umbilical sepsis
9. Trophoblastic disease
1) Vesical drift
2) placental transfusion syndrome
3) adenocarcinoma
4) invasive vesical drift
5) choriocarcinoma
10. Morphological signs of hemolytic disease
1) arteritis and phlebitis umbilical vessels
2) brown atrophy of the liver
3) hemolytic jaundice
4) anemia and edema
5) kernicterus
11. Morphological characters intrauterine hypoxia
1) thrombotic complications
2) diapedetic hemorrhage and edema
3) aspiration of amniotic fluid
4) depression of the respiratory center of the brain
5) meconium in the amniotic fluid
12. Morphological characters of postmaturity
1) calcification of the placenta
2) absence of lubrication
3) dry skin with maceration
4) the appearance of ossification centers in the proximal epiphysis of the tibia
and humerus
5) loss of the umbilical cord
13. Morphological manifestations of mucoviscidosis
1) hemorrhagic syndrome
2) retention cysts of pancreas and other organs
3) secondary fibrosis
4) jaundice
5) cirrhosis
14. morphological signs of prematurity
1) the absence of ossification centers in the epiphysis
2) imperforate fontanelles
3) soft skull bones
4) the absence of vellus hair, face, shoulders, back,
5) underdevelopment of the nail plate
ORENBURG STATE MEDICAL UNIVERSITY
DEPARTMENT OF PATHOLOGICAL ANATOMY
METHODICAL MANUAL FOR PRACTICAL TRAINING FOR STUDENTS OF
FOREIGN FACULTY
THEME:
GASTROINTESTINAL TRACT DISEASES
GASTROINTESTINAL TRACT DISEASES
Gastritis is an inflammation of the gastric mucosa, developed with the direct
impact of pathogenic irritants to the mucous membrane, and indirectly through
neurohumoral factors. Forms of acute gastritis: a simple catarrhal, erosive haemorrhagic, purulent, fibrinous, necrotic.
Chronic gastritis is characterized by pathological stimuli exposure time and leads
to the development of sclerotic and atrophic processes in the mucosa.
There are: autoimmune, bacterial, and reflux gastritis.
Autoimmune gastritis is often localized in the body and the bottom of the
stomach, and not infrequently combined with other autoimmune diseases. It is
characterized by the presence of autoantibodies to parietal cells of the gastric
glands and intrinsic factor. There the disappearance of the parietal cell in the antral
zone, hyperplasia cells G- and gastrinemiya, reducing the HCL and 10% of
patients develop pernicious anemia.
Bacterial gastritis are Localized in the antrum and arises against colonization by
Helicobacter pylori, which gives support regeneration and chronic inflammation.
Reflux gastritis develops when casting duodenal contents into the stomach.
Morphological forms of chronic gastritis: chronic superficial, atrophic gastritis
without defeat glands, atrophic gastritis with the defeat of the glands without
atrophy, atrophic gastritis with atrophy of the glands and the restructuring of the
epithelium.
Long existing chronic gastritis leads to increased mitotic activity of the epithelium
of cervical glands, violation of their differentiation and the emergence of
cylindrical cells of the suction type, alternating with goblet cells. The restructuring
of the intestinal type called enterolisation. The glands of the body and the bottom
are exposed pyloric metaplasia. The progression of the process often leads to the
development of dysplasia with further malignancy. Chronic atrophic gastritis with
the restructuring refers to precancerous epithelial disease.
Peptic ulcer is a chronic disease, which is the morphological substrate of recurrent
ulcer. The ulcer is a defect in the form of niches in the gastric mucosa, extends
beyond the muscle plate. It passes the stage of erosion, acute ulcers and chronic
ulcers. This is called an ulcer peptic ulcer as a result of developing the destructive
action of gastric juice. Localized mainly along the lesser curvature between the
body and the prelude to the stomach. Erosion is a defect does not penetrate the
mucous membrane of the muscle beyond the plate. Acute ulcers occur in any area
of the stomach, multiple, up to 1 cm in size, penetrate to different depths, with
jagged edges and the bottom painted black.
Stomach cancer is more often localized in the pyloric region. Microscopically
distinguish two types: intestinal and diffuse. Intestinal cancer develops from the
epithelial cells of the stomach exposed enterolisation. This tumor is characterized
by a high degree of differentiation among the histological types of adenocarcinoma
predominates. Stomach cancer develops from diffuse types of epithelial cells have
not undergone metaplasia. Tumor structure with a low degree of differentiation
prevail - signet ring cell, scirrhous, small cell lung cancer.
Ulcerative colitis - systemic disease with a predominance of the inflammatory
process in the colon. Ulcerative colitis extends from the rectum proximally. In
many patients, it is combined with arthritis, inflammation of the sacroiliac joint,
ankylosing spondylitis, uveitis, sclerosing cholangitis, and skin lesions.
Crohn's disease is a granulomatous disease affecting mainly the terminal ileum.
However, the process may involve any of the digestive tract. There may be
changes in the system as a migratory polyarthritis, sacroiliitis, spinal lesions with
the development of ankylosis, erythema nodosum, thickening of the tips of the
fingers as drumsticks. Crohn's disease and ulcerative colitis are referred to as
idiopathic diseases, pathogenesis of which is the inability of the immune system of
the intestine, maintain homeostasis of the intestinal mucosa and regulating
inflammatory reactions adequately respond to antigens. The result of this disparity
is immune-mediated damage.
Appendicitis is an inflammation of the appendix cecum, with a peculiar clinical
picture. There are acute and chronic appendicitis. In morphology: simple,
superficial and destructive forms of: phlegmonous, ulcerative phlegmonous,
gangrenous and appostematous.
CONTROL QUESTIONS
1. Inflammation and damage to salivary gland tumor. Sialadenitis, sialolithiasis:
etiology, pathogenesis pas, morphology, outcomes. Benign and malignant tumors,
tumor-like diseases. Classification, morphological characteristics, complications,
prognosis.
2. Diseases of the esophagus. Diverticula of the esophagus (congenital and
acquired). Ruptures of the esophagus (Mallory-Weiss syndrome). Esophagitis.
Barrett's esophagus. Etiology, morphogenesis, clinical and morphological
characteristics, complications, outcomes.
3. Tumors of the esophagus. Benign tumors: classification. Malignant tumor.
Cancer of the esophagus, morphological characteristics, complications, outcomes,
prognosis.
4. Diseases of the stomach. Gastritis. Definition. Acute gastritis. Etiology,
pathogenesis, morphological forms. Clinical and morphological characteristics.
5. Chronic gastritis, the essence of the process. Etiology, pathogenesis. Principles
of classification. Forms allocated on the basis of the study gastrobiopsy,
morphological characteristics. Complications, outcomes, prognosis. Chronic
gastritis as a precancerous condition.
6. Peptic ulcer disease. Definition. General characteristics of peptic (chronic)
ulcers of different locations. Epidemiology, etiology, morphogenesis.
Morphological characteristics of chronic ulcers in the period of exacerbation and
remission. Complications, outcomes. Acute gastric ulcers: etiology, pathogenesis,
morphological characteristic,outcomes.
7. Tumors stomach. Classification. Hyperplastic polyps. Adenoma of the stomach.
Morphological characteristics. Malignant tumors of the stomach. Stomach cancer.
Epidemiology, etiology, classification principles. Features metastasis. Macroscopic
and histological forms.
8.Sindromy malabsorption. The role of the morphological study biopsy in the
diagnosis of diseases of the colon.
9. Whipple's disease. Ulcerative colitis. Crohn's Disease. Etiology, morphogenesis,
morphological ical characteristics, complications, outcomes, prognosis. The
criteria for the differential diagnosis of chronic colitis.
10. Appendicitis. Classification, etiology, classification. Morphological
characteristics of appendicitis. Complications. Features of the disease in children
and the elderly.
The practical part of the subject:
Slides. In the study micropreparations pay attention to the education elements,
designated by the letters in parentheses.
1. Chronic gastric ulcer during the exacerbation. H & E stain. In the area of
the defect of the stomach wall has a fibrinous-purulent exudate (a) to be an
extensive area of fibrinoid necrosis (b), the presence of granulation tissue (c),
and the growth of coarse fiber connective tissue, penetrating to different depths
of the muscular layer (d). Serous membrane of the stomach wall preserved (e).
2. Adenocarcinoma. H & E stain. All the layers of the stomach wall infiltrated
tumor tissue with signs of cell irregularities (a). Abnormal mitoses seen in
multiple hyperchromatic (b) and polymorphic tumor cells (c).
3. Crohn's disease. H & E stain. The wall of the colon has ulcer (1) penetrating
into the muscular layer in the mesentery tissue, forming a fistulous tract (2).
Lymphoplasmacytic inflammatory infiltrate (3) applies to all membrane of the
intestinal wall, preserving architectonic crypts and the number of goblet cells.
Thickened bowel wall due to edema, inflammatory infiltrate (4) areas of
fibrosis and hypertrophy of the muscle membrane (5). Reveals a granuloma (6),
composed of epithelioid and giant cell type Pirogov-Langhans (7) surrounded
by a belt of lymphocytes, without clear boundaries (8). Unlike the granulomas
in sarcoidosis, no fibrous ring and from tuberculous granulomas - no cheesy
necrosis.
4. Phlegmonous appendicitis. H & E stain. All the layers of the wall of the
appendix is diffusely infiltrated with polymorphonuclear leukocytes (a). There
are abundant fibrinous deposits in the serous membrane (b). In the lumen of the
process of accumulation of pus (c). The mesentery of the appendix congestion
of vessels and inflammatory infiltration - mezenteriolit (g).
macropreparations:
1. Acute catarrhal gastritis: in preparation stomach mucosa is thickened,
congested with high folds, covered with thick viscous mucus, with petechial
hemorrhages. Causes: poor quality food, drinking alcohol surrogates,
antineoplastic chemotherapy, burns, acids and alkalis, uremia, salmonellosis,
shock, severe stress.
Complications: acute ulcer, the transition to chronic gastritis.
2. Erosions and acute gastric ulcer: in Preparation stomach mucosa swelling,
on the surface there are multiple petechiae and conical shape defects of
different sizes, their bottom edges and black. Erosions localized within the
mucosa and ulcers penetrate to different depths of the mucosa, and some reach
the muscle membrane. The reasons: endocrine disease (Zollinger-Ellison
syndrome, hyperparathyroidism), acute and chronic circulatory disorders,
poisoning, allergies, chronic infections (tuberculosis, syphilis), postoperative,
steroid and stress ulcers
Complications of perforation, peritonitis.
Outcome: erosion epiteliziruyutsya, ulcerative defect is replaced by scar tissue.
3. Chronic gastric ulcer in remission: in preparation stomach on the lesser
curvature has a pathological lesion in a recess of the mucous membrane, a
rounded shape, the size of 3 cm in diameter. In the context of the inlet hole
crater smaller than the inside of the ulcer. Edge facing a cardia undermining the
mucous membrane over it hangs. Edge facing away gatekeeper sloping,
terraced. Column ulcers presented connective tissue, gray-white, 2.5 cm. At the
bottom of the ulcer sclerotic vessels, clearance of their gapes.
Causes: genetic predisposition, Helicobacter pylori, and disregeneratornye
inflammatory mucosal changes, the effects of the factors leading to peptic
aggression (hydrochloric acid and pepsinogen).
Complications: perigastrit, bleeding, perforation, penetration, scar deformity of
the stomach with the development of stenosis input or output openings. Against
the backdrop of a chronic ulcer may develop a second disease - cancer of the
stomach.
4. stomach polyps (adenomas). in the antrum, there are two tumor formation
size of a pigeon egg on thin legs, irregular oval shape with villous surface, soft
consistency. In the context of pathological growths richly vascularized and
localized exclusively on the mucosal surface, not germinating underlying
tissues.
Complications: bleeding, obstruction of output or inlet.
Outcome: malignancy.
5. Various forms of stomach cancer. a) Mushroom cancer: at mucosal
surfaces has tumor formation, growing into the gastric lumen, irregularly
rounded shape measuring 5 cm in diameter, on a broad base in the form of a
mushroom cap with the retraction of the center. In the section shows that the
entire tumor invades the stomach wall.
b) diffuse gastric cancer: the body is reduced in size, the wall throughout the
thickened up to 1cm thick 'woody' consistency on the cut shows a pinkish-gray
tissue. The mucous membrane is uneven, it folds of varying thickness, serosa is
thickened, dense, hilly. The lumen of the stomach contractions.
Causes: food (smoked, canned, pickled vegetables, pepper), biliary reflux (after
operations on the stomach, especially Billroth II), Helicobacter pylori
(promotes mucosal atrophy, intestinal metaplasia, dysplasia).
Metastasis: 1. orthograde nodal metastases in regional nodes in the small and
large curvature, retrograde nodal metastases in the left supraclavicular lymph
node - metastasis Virchow, in the ovaries - Krukenberg cancer, adrectal fiber metastases Schnitzler.
2. Hematogenous metastases to the liver, lungs, brain, bones, kidneys, adrenal
glands and less frequently in the pancreas. 3. Implantation - carcinomatosis of
the pleura, pericardium, diaphragm, peritoneum, omentum.
6. Ulcerative Colitis. In colon preparation with sharply sanguineous mucosa.
Along the mucosal erosions and ulcers of various changes in size and shape.
The bottom of the ulcers clean without festering overlays, covered with a thin
layer of fibrin brilliant. The surviving islets mucosa numerous pseudopolyps
small size (0.2 cm - 0.5 cm), with no clear division into the leg and body with a
smooth surface.
Causes: genetic predisposition, disturbance cenosis bacterial, viral or bacterial
beginning, an autoimmune reaction to antigens, food allergy, changes in the
immunological reactivity.
Intestinal complications: toxic dilatation of the colon, perforation, gangrene.
Extraintestinal complications: skin lesions (erythema, nodular, massive leg
ulcers, gangrenous pyoderma), arthritis, eye damage (episcleritis, uveitis,
iridocyclitis), rarely sepsis, amyloidosis, pericholangitis with the development
of fibrotic changes with the outcome of biliary cirrhosis.
The outcome: a partial or complete epithelialization of ulcers, the formation of
scar tissue within the mucosa. Against the background of epithelial dysplasia
may develop cancer.
7. Crohn's disease. The preparation portion of the transverse colon, descending
colon, the mucosa on the cut even near ulcers -Pink pale color. There is an
alternation of the affected areas with no changes in the mucous. Deep slit-like
ulcers are oriented along and across the axis of the colon are smooth and not
saped edge and preserved between the areas of edematous mucosa attached to
the surface of the colon similar to the "cobblestone street". Characteristically
segmental narrowing of the intestinal lumen extending from 5 cm to 10 cm "threadlike colon." Some ulcers penetrate the muscular layer, forming a fistula
connecting the different parts of the colon and small intestine. Serous
membrane dull, gray, edematous mesentery, there are extensive adhesions
between loops of intestine.
Causes: genetic predisposition, disturbance cenosis bacterial, viral or bacterial
beginning, autoimmune reaction to hypertension, a food allergy, the change of
immunological reactivity.
Complications: perforation in the free abdominal cavity fistulas with the outlet
on the skin of the abdominal wall, fistulas connecting the intestine to the
bladder, uterus, stomach, rectal fistula.
Outcome: Strictures fine, colon and rectum occur in ¼ of patients. Cancer on
the background of Crohn's disease less often than with ulcerative colitis.
8. Phlegmonous appendicitis. Appendix enlarged and thickened to 1.5 cm in
diameter, with serosa dull gray overlays fibrin. Mesenteric vessels congested. In
the context of appendiceal lumen process with accumulation of purulent
exudate impregnating the entire wall.
Reasons: circulatory disorders, obstruction of the lumen, followed by
compression of the veins and the development of ischemia, infection.
Complications: ulceration, perforation, paraappendicitis, mezenteriolit,
gangrenous inflammation, peritonitis, liver abscesses.
Test control
Select one or more correct answers
1. The symptoms of acute catarrhal gastritis
1) mucosal thickening
2) atrophy of the glands
3) multiple erosions
4) mucous sclerosis
5) neutrophilic infiltration of the mucous
6) mucosal lymphoid infiltration
2. morphological forms of acute gastritis
1) fibrinous
2) atrophic
3) hypertrophic
4) catarrhal
5) Corrosive (necrotic)
3. changes in the epithelium in chronic gastritis
1) atrophy
2) intestinal metaplasia
3) hyperplasia
4) dysplasia
4. Clinical and morphological signs of chronic atrophic gastritis in the acute
stage
1) occurs frequently in patients with alcoholism
2) the mucosa is not changed
3) diffuse lymphoid infiltration plasmocytic with considerable admixture of PMN
4) focuses pyloric and intestinal metaplasia
5) gastric hyperacidity
5. Sclerotic deformation of stomach is the outcome
1) catarrhal gastritis
2) diphtheritic gastritis
3) corrosivity gastritis
4) abscess gastritis
6. Local factors in the development of gastric ulcer
1) increase the aggressiveness of gastric juice
2) campylobacter
3) presence of chronic gastritis
4) poor circulation
5) All the answers are correct
6) All the answers are incorrect
7. CAUSES OF ACUTE stomach ulcers
1) corticosteroids
2) Stress
3) Aspirin
4) Smoking
5) increasing vagal tone
8. Signs of chronic gastric ulcer during the exacerbation
1) the presence of fibrinopurulent exudate on the surface
2) scar tissue interrupts muscle membrane at different depths
3) endangitis
4) fibrinoid changes in vascular walls and in the bottom of ulcers
5) The deepest zone is located is represented by coarse fiber ulcer scar tissue
9. MECHANISM OF BLEEDING IN ULCER
1) arrosive
2) diapedetic
3) due to rupture of the vessel
4) as a result of purulent fusion
10. Complications of chronic ulcers
1) penetration
2) perforations
3) empyema
4) hypercalcemia
5) scarry stenosis and deformation of the wall
6) bleed
11. Benign tumors STOMACH
1) angiosarcoma
2) adenoma
3) leiomyoma
4) adenocarcinoma
12. ADENOMA THIS IS
1) benign tumor of glandular epithelium
2) malignant tumor of glandular epithelium
3) epidermal cancer
4) malignant tumor of the transitional epithelium
5) benign tumor of squamous epithelium
13. Microscopic characteristics scirrhous stomach cancer
1) atypical cells with large nuclei are arranged in groups
2) atypical cells form cancer
3) massive proliferation of connective tissue
4) the abundance of mucus in the lumen of the glands
5) atypical cancer cells do not form
14. COMPLICATIONS OF GASTRIC CANCER
1) hemoptysis
2) dilation of the pylorus
3) perforation
4) depletion
5) gastric bleeding
15. The cause of development of appendicitis
1) blockage of coprolites
2) appendicular artery thrombosis
3) obstruction of gallstones
4) compression of the veins process
5) microbial flora
16. The characteristic signs of ulcerative colitis
1) the place of defeat - rectum
2) chronic inflammation affects the entire thickness of the bowel
3) the mucous membrane looks like a cobblestone street
4) is characterized by crypt abscesses
5) characterized pseudopolyps
6) often leads to the development of colon cancer
7) is often complicated by fistulas interintestinal
17. Characteristic signs CROHN'S DISEASE
1) the place of defeat - rectum
2) chronic inflammation affects the entire thickness of the bowel
3) the mucous membrane looks like a cobblestone street
4) is characterized by crypt abscesses
5) characterized pseudopolyps
6) often leads to the development of colon cancer
7) is often complicated by fistulas interintestinal
18. morphological characters CROHN'S DISEASE
1) is characterized by segmental defeat cancer, "Hose stricture"
2) crypt abscesses
3) fibrinous plaques on the mucous membranes
4) atrophy of the mucosa
5) Noncaseating granulomas
19. morphological signs of ulcerative colitis
1) ulcerative process within the mucosa
2) lymphoplasmacytic infiltrate all layers of the bowel wall
3) deep ulcers to the muscle layer
4) crypt abscesses
5) lymphoplasmacytic infiltration of the lamina propria with an admixture of
eosinophils and leukocytes
20. The cause of development of ischemic colitis
1) Atherosclerosis mesenteric arteries
2) nonbacterial thrombotic endocarditis
3) the absence of ganglion cells in the submucosal layer
4) systemic vasculitis
5) Meckel's diverticulum
21. Morphological changes in ischemic colitis
1) hemorrhagic infarction
2) gangrene
3) megacolon
4) the proliferation of granulation tissue with subsequent fibrosis
5) polyposis mucosa
LUNG DISEASES
Acute inflammatory diseases of the lung
Pneumonia is the acute inflammatory lung disease of an infectious nature, mainly
affecting the respiratory departments, different pathogenesis and clinical and
morphological manifestations.
The main causative agent of pneumonia - Streptococcus pneumoniae (82
serological variants), reveals more than 90% of cases, 25% of pneumonia is
Mycoplasma pneumoniae, and other bacteria: Klebsiella, Pseudomonas aeruginosa,
bacillus Pfeiffer, streptococci, staphylococci, E. coli, Proteus, Haemophilus
influenzae, a mixed flora, viruses, fungi.
Ways of penetration of bacteria into the lungs: airborne and aspiration combined
with damage to lung protection barrier systems, hematogenous, contagious.
Classification:
1. Pathogenesis:
- Primary pneumonia developed in the absence of any lung disease and diseases of
other organs and systems, which can contribute to its occurrence.
- secondary pneumonia, occur against a background of chronic lung disease, as
well as somatic or infectious diseases with the localization of primary affect out of
lung.
2.
clinical
and
bronchopneumonia
pneumonitis).
morphological
characteristics:
lobar
(croupous),
(lobular) and acute interstitial pneumonia (acute
3. Distribution: acute pneumonia may be single or double-sided; acinar, miliary,
drain-focal, segmental, polysegmental, and total;
4. By the nature of the flow: severe, moderate, light; acute and protracted.
Lobar (croupous) pneumonia is an acute infectious and allergic inflammatory
disease of the lung with a lesion lobe involved in the visceral pleura and the
formation of fibrinous exudate.
Etiology: pneumococci types 1, 2 and 3, at least diplobatsilla Friedlander
(Klebsiella).
Way of infection - airborne. In the pathogenesis of leading a hypersensitivity
reaction of immediate type, growing on the territory of the departments of
respiratory lung, including the alveoli and alveolar ducts.
Lobar pneumonia in the classic version takes place in 4 stages.
1.
In the first stage of congestion develops within 1 day of the disease,
characterized by severe congestion of alveolar capillaries, interstitial edema and
fluid accumulation of fluid containing a large amount of microbes isolated alveolar
macrophages and polymorphonuclear leukocytes. The bronchi are intact. The
pleura edema and inflammatory changes. The proportion of full-fledged
lightweight, sealed.
2.
Stage of red hepatization develops on the 2nd day of illness. The exudate
appear a large number of red blood cells, isolated polymorphonuclear leukocytes,
macrophages, falls fibrin. Startled share airless, tight, red, reminiscent of the liver
tissue. The pleura is thickened, with fibrinous deposits.
3.
Stage gray hepatization takes 4-6 day illness. In this period the spadenie
pulmonary capillaries in exudate polymorphonuclear leukocytes, macrophages and
fibrin. The affected lobe of the lung is increased in size, heavy, dense, airless, on
the cut with a grainy surface. The pleura is thickened, opaque with fibrinous
deposits.
4.
Stage resolution comes on the 9-11 th day of illness. Fibrinous exudate
subjected to melt under the influence of proteolytic enzymes, and granulocytemacrophage phagocytosis. Exudate eliminated by the lymphatic drainage of the
lung and is separated from the sputum. Fibrinous deposits on the pleura resolve.
Bronchopneumonia (lobular pneumonia), characterized by the development in the
pulmonary parenchyma foci of acute inflammation in size from acinar up segment,
associated with damage to the bronchioles. Disease is preceded by inflammation of
the bronchi with the violation of the drainage function that facilitates the
penetration of microbes in the respiratory department of lungs - alveolar ducts and
alveoli. It is also possible peribronchial and hematogenous way.
Morphological changes in the lung depends on the type of pathogen. By
stereotyped changes include the formation of inflammatory focus around the small
bronchi and bronchioles with symptoms of bronchitis and / or bronchiolitis
submitted to various forms of catarrh. In the gaps of the alveoli and bronchioles
and bronchi accumulated exudate (serous, purulent, hemorrhagic, or mixed), the
form of which is determined by the severity and etiology of the disease process. On
the periphery of foci located Intact lung tissue with signs of perifocal emphysema.
Macroscopically detected airless dense foci of various sizes, usually formed around
the bronchial lumen which is filled with liquid contents turbid red-gray and
localized usually in back and low back lung segments (II, VI, VIII, IX and X).
Acute interstitial pneumonia (acute pneumonitis) is characterized by initial
development of acute interstitial inflammation in the lungs and respiratory
departments in the alveolar wall with the possible formation of a secondary fluid in
the lumen of the alveoli and bronchioles.
The etiology associated with viruses, mycoplasma, legionella, fungi,
Pneumocystis, and often remains unknown. Pathogenesis: the primary lesion
pneumocytes 1- and 2-order and capillary endothelium, which is accompanied by
the development in the area of acute inflammation.
Morphological manifestations: damage and regeneration of the alveolar epithelium,
alveolar capillary congestion, inflammatory infiltration of the alveolar walls, the
accumulation of protein in the fluid lumens alveoli often with the formation of
hyaline membrane, with a touch of polymorphonuclear leukocytes and
macrophages, sometimes with characteristic inclusions. The outcome: most
recovery; the development of interstitial fibrosis.
LUNG ABSCESS
The term “pulmonary abscess” describes a local suppurative process within the
lung, characterized by necrosis of lung tissue. Oropharyngeal surgical procedures,
sinobronchial infections, dental sepsis, and bronchiectasis play important roles in
their development.
Etiology and Pathogenesis.
Although under appropriate circumstances any pathogen can produce an abscess,
the commonly isolated organisms include aerobic and anaerobic streptococci, S.
aureus, and a host of gram-negative organisms. Mixed infections often occur
because of the important causal role played by inhalation of foreign material.
Anaerobic organisms normally found in the oral cavity, including members of the
Bacteroides, Fusobacterium, and Peptococcus species, are the exclusive isolates in
about 60% of cases. The causative organisms are introduced by the following
mechanisms:
•
Aspiration of infective material (the most frequent cause): This is
particularly common in acute alcoholism, coma, anesthesia, sinusitis,
gingivodental sepsis, and debilitation in which the cough reflexes are
depressed.
•
Antecedent primary lung infection: Post-pneumonic abscess formations are
usually associated with S. aureus, K. pneumoniae, and the type 3
pneumococcus. Posttransplant or otherwise immunosuppressed individuals
are at special risk.
•
Septic embolism: Infected emboli from thrombophlebitis in any portion of
the systemic venous circulation or from the vegetations of infective bacterial
endocarditis on the right side of the heart are trapped in the lung.
•
Neoplasia: Secondary infection is particularly common in the
bronchopulmonary segment obstructed by a primary or secondary
malignancy (postobstructive pneumonia).
•
Miscellaneous: Direct traumatic penetrations of the lungs; spread of
infections from a neighboring organ, such as suppuration in the esophagus,
spine, subphrenic space, or pleural cavity; and hematogenous seeding of the
lung by pyogenic organisms all may lead to lung abscess formation.
When all these causes are excluded, there are still cases in which no reasonable
basis for the abscess formation can be identified. These are referred to as primary
cryptogenic lung abscesses.
Morphology. Abscesses vary in diameter from lesions of a few millimeters to
large cavities of 5 to 6 cm. They may affect any part of the lung and may be
single or multiple. Pulmonary abscesses due to aspiration are more common on
the right (because of the more vertical right main bronchus) and are most often
single. Abscesses that develop in the course of pneumonia or bronchiectasis are
usually multiple, basal, and diffusely scattered. Septic emboli and pyemic
abscesses are multiple and may affect any region of the lungs.
The abscess cavity might be filled with suppurative debris. If there is
communication with an air passage, the contained exudate may be partially
drained to create an air-containing cavity. Superimposed saprophytic
infections are prone to flourishing within the already necrotic debris of the
abscess cavity. Continued infection leads to large, fetid, green-black,
multilocular cavities with poor demarcation of their margins, designated
gangrene of the lung. The cardinal histologic change in all abscesses is
suppurative destruction of the lung parenchyma within the central area
of cavitation . In chronic cases considerable fibroblastic proliferation
produces a fibrous wall.
The course of abscesses is variable. With antimicrobial therapy, most resolve
leaving behind a scar. Complications include extension of the infection into the
pleural cavity, hemorrhage, the development of brain abscesses or meningitis from
septic emboli, and (rarely) secondary amyloidosis (type AA).
Chronic diffuse lung disease - a group of lung diseases of various etiology,
pathogenesis and morphology, in which the characteristic of the development of
chronic cough with sputum and paroxysmal or permanent shortness of breath that
is not associated with specific infectious diseases, especially tuberculosis of the
lungs.
Chronic diffuse lung disease in accordance with the functional and morphological
features of lung lesions are divided into three groups: obstructive, restrictive,
mixed.
Chronic obstructive pulmonary disease - a disease airways, characterized by
increased resistance to air flow due to partial or complete obstruction of them on
any level.
At the heart obstructive pulmonary disease is a violation of the drainage function
of bronchi. There are: chronic obstructive pulmonary emphysema, chronic
obstructive bronchitis, bronchiectasis bronchial asthma.
Restrictive lung disease characterized by the decline in lung parenchyma with a
decrease in lung capacity, against the development of inflammation and fibrosis in
the interstices of respiratory portions of the lungs, leading to block blood barrier
and progressive respiratory failure.
Morphogenesis: Bronhitogenic mechanism due to violation of the drainage
function of the lungs and bronchial obstruction and leads to obstructive lung
diseases. Pnevmoniogenic mechanism associated with bronchopneumonia, lobar
pneumonia and complications - and abscess formation carnification, expressed in
the outcome of a restrictive component. Pnevmonitogenic mechanism defines
chronic inflammation and fibrosis in the territory of interstitial of lung and
respiratory departments found in interstitial lung disease.
In the final developing pulmonary fibrosis (pnevmocirrhosis), secondary
pulmonary hypertension, right ventricular hypertrophy of the heart and pulmonary
heart disease. Chronic diffuse lung disease are underlying conditions for the
occurrence of lung cancer.
Chronic obstructive bronchitis - a disease characterized by hyperplasia and
excessive mucus production of bronchial glands, which leads to a productive
cough for at least 3 months per year for 2 years. Smoking - the most important
etiological factor of chronic bronchitis.
Classification by 3 criteria: a) the presence of bronchial obstruction - simple and
obstructive. Obstructive chronic bronchitis is characterized by a simple obstruction
of the peripheral parts of the bronchial tree as a result of inflammation of the
bronchial tubes; b) the form of inflammation; c) the distribution process - local
(bronchial II, IV, VIII, IX, and X segments, especially of the right lung) and
diffuse.
Grossly - bronchial walls become thickened, surrounded by layers of connective
tissue, sometimes marked bronchial distortion. In the long chronic bronchitis can
occur saccular and cylindrical bronchiectasis - expanding the bronchial lumen.
Microscopic changes: in the wall of the bronchus expressed cellular inflammatory
infiltrate, abnormal regeneration (metaplasia), proliferation of granulation tissue,
that can lead to inflammatory polyps bronchial mucosa, muscular atrophy and
sclerosis plate mucosa. Hyperplasia of the mucous glands is one of the main
morphological signs of chronic bronchitis.
Complications: pneumonia, atelectasis foci, obstructive pulmonary emphysema
and pulmonary fibrosis.
Bronchiectasis - a disease characterized by a certain set of pulmonary and
extrapulmonary changes (chronic obstructive pulmonary disease with symptoms of
tissue hypoxia and the development of pulmonary heart) in the presence of
bronchiectasis in the bronchi.
Bronchiectasis - a persistent pathological bronchodilation with the destruction of
elastic and muscular layers of the bronchial wall contains a cartilaginous plate and
mucous glands. Bronchiectasis may be congenital or acquired (local).
Grossly isolated saccular bronchiectasis, which are located mainly at the level of
the proximal bronchi, including bronchial 4th order. Cylindrical bronchiectasis are
formed at the level of the bronchi 6-10-order. Represented as a series of
interconnected hollow cylindrical shape extensions. Varicose bronchiectasis
resemble varicose veins.
Microscopically in the cavity bronchiectasis detected purulent exudate containing
microbial body and desquamated epithelium. The basement membrane surface
epithelium hyalinized has a corrugated appearance. Places represented epithelium
basal cells, foci of squamous metaplasia and polyposis. The bronchus cartilage
degeneration, atrophy and the destruction of elastic and muscular layers, sclerosis
and diffuse infiltration of all layers gistiolimfotsitarnaya wall bronchiectasis with
an admixture of polymorphonuclear leukocytes. In the adjacent lung parenchyma
defined field fibrosis foci obstructive pulmonary emphysema.
Extra-pulmonary syndrome when bronchiectasis due to hypoxia and the
development of hypertension in the pulmonary circulation: the deformation of the
distal phalanges of the nail as "drumsticks", change the nail plate of the type of
"watch glasses", "warm" cyanosis. Hypertension in the pulmonary circulation leads
to right ventricular hypertrophy and the development of pulmonary heart.
Chronic obstructive pulmonary emphysema.
Emphysema - a concept associated with the expansion rack pneumatic spaces distal
to the terminal bronchioles in violation of the integrity of interalveolar septums.
Etiology: the presence of chronic obstructive bronchitis, in addition, there is a
definite genetic predisposition to this disease, clutch M-gene leads to low levels of
serum α1-antitrypsin deficiency - a protease inhibitor that destroy connective tissue
carcass of interalveolar septums. The main source of this enzyme - hepatocytes and
bronchiolar exocrine cells (Clara cells).
Morphological variations:
Centriacinar emphysema is caused by the prevalence of respiratory bronchioles
and expansion of alveolar ducts, while the peripheral parts of the lobes remain
relatively intact.
At panacinar emphysema in the process involves both central and peripheral parts
of the acini. This unit is formed by blood barrier wears off of interalveolar of
interalveolar sclerosis and capillary walls to the rapid development of severe
ventilatory failure.
At paraseptalemphysema changed the whole acinar distal portion, the proximal
part of the same looks unchanged. Most often it occurs in the upper lobes of the
lung, and the subpleural regions of fibrosis around the outbreaks. Progression of
the disease can lead to the formation of cystic cavities filled with air, up to several
centimeters in diameter - bulls, which served as a basis to call the process in lung
bullous emphysema.
At irregular emphysema acinus struck unevenly, and clinical manifestations of
emphysema, as a rule, lacking. Complications include progressive pulmonary heart
disease quickly leads to death in the absence of oxygen therapy and other modern
methods of treatment.
Interstitial lung disease - a heterogeneous group of diseases characterized by a
predominance of diffuse interstitial pulmonary respiratory lesions of the lungs,
especially the alveoli and bronchioles. A typical morphological manifestations of
interstitial disease is fibrosing alveolitis. It is a pathological process characterized
by diffuse or focal, acute or chronic purulent inflammation with the outcome of
fibrosis.
Common features for all interstitial lung diseases is the development of the disease
in the early alveolitis and interstitial fibrosis in the final of the disease. An extreme
expression of interstitial fibrosis is the formation of " honeycomb fibrosis".
The reasons: viruses, bacteria, fungi, organic and inorganic dust, radionuclides,
hyperoxia in a hyperbaric oxygen, toxic factors, drugs and others., As well as
interstitial lung disease of unknown etiology.
Acute interstitial pneumonitis - a group of interstitial lung disease with unknown
etiology, characterized by progressive pulmonary insufficiency. Most occur in the
age range 30-50 years. The group includes idiopathic fibrosing alveolitis: classical
interstitial pneumonia, "nonspecific" interstitial pneumonia, desquamative
pneumonia, bronchiolitis obliterans with organizing pneumonia, giant cell
interstitial pneumonia. The disease occurs phasically. Initial stage: The
macroscopic changes: uneven light air, full-blooded, with increased density.
Microscopic manifestation: in interalveolar septums are found in the phenomenon
of edema, inflammatory infiltration and initial manifestations of sclerosis
Late stage: macroscopic changes: seal lung tissue, acquiring rubber density,
lowering lightness and elasticity to the formation of cellular structures that
resemble honeycombs - "honeycomb fibrosis ". Microscopic examination revealed
marked sclerosis, interstitial lung and respiratory departments cystic reconstruction
of the lung tissue with squamous metaplasia, dysplasia, and in some cases the
formation of centers of adenomatosis. Blood barrier is blocked and does not
function due to both interstitial fibrosis of interalveolar septa and
disregeneratornyh changes in the epithelial lining.
Sarcoidosis - a systemic disease characterized by the development of noncaseating
granulomas with unknown etiology, in the lungs, lymph nodes and other organs
(skin, liver, spleen, eye). Sarcoidosis of the lungs characterized by minimal
intensity fibrosing alveolitis weak lymphohistiocytic infiltration and typical sarcoid
granulomas immune type, consisting of macrophages, epithelioid and giant
multinucleated cell type Langhans, CD4 + T lymphocytes and fibroblasts. A
characteristic feature of sarcoid granulomas are the absence of caseous necrosis,
"pressed" look by peripherally located fibroblasts and collagen and uniform
morphology.
Silicosis - interstitial granulomatous disease related to pneumoconiosis group dust professional lung diseases induced by mineral dust. It is related to exposure to
light particles of quartz dust, which cannot digest alveolar macrophages.
Macrophage activation, they generate reactive oxygen species, inflammatory
cytokines (IL-1 and TNF), lead to damage and fibrosis of the lung tissue.
Macrophage while dying, and silicon particles were once again in the lung tissue,
causing changes again. Silicosis is characterized by diffuse and nodular
pneumosclerosis.
lung Cancer
Cancer is 90- 95% of all lung tumors, about 5% - carcinoids and 2-5% - tumors of
mesenchymal origin.
Etiology. In 98% of cases the etiology is associated with exposure to exogenous
carcinogenic agents (smoking, occupational hazards, radiation), and only in rare
cases - to genetic factors. Pathogenesis and morphogenesis: involve a violation of
proliferation, differentiation and apoptosis in epithelial cells under the action of
carcinogens, the appearance of foci of hyperplasia, metaplasia, and dysplasia,
bronchial, bronchiolar and alveolar epithelium. The key to the pathogenesis of lung
cancer is damage to the epithelial cell genome.
Classification of lung cancer.
By localizing release: 1) root or central (stem, lobar bronchi and proximal
segmental bronchus; 2) peripheral (bronchi of smaller caliber, bronchioles and
alveoli, and 3) mixed (solid) cancers.
By the nature of growth distinguished: 1) exophytic (endobronchial); 2) endophytic
(exobronchial and peribronchial) cancer.
On the macroscopic form of: 1) plaqueformus; 2) polypoid; 3) diffuse
endobronchial; 4) nodular; 5) branched; 6) nodular-branched; 7) cavity; 8)
pnevmoniopodobny cancer.
In microscopic view (histogenesis): 1) squamous; 2) small-cell; 3)
adenocarcinoma; 4) large cell carcinoma 5) glandular squamous cell carcinoma; 6)
cancer of the bronchial glands: adenoid cystic carcinoma, 7), neuroendocrine
carcinoma (carcinoid).
1.
2.
3.
4.
5.
6.
CONTROL QUESTIONS
Acute inflammatory lung disease. The role of homeostasis in the
development of lung pneumonia. Classification of pneumonia. Pneumonia
under immunosuppression. The concept of nosocomial infections, the
causes.
Bacterial pneumonia. Classification. Focal pneumonia (bronchopneumonia).
The etiology and pathogenesis, morphological features. Complications focal
pneumonia outcomes.
Lobar (croupous pneumonia). Etiology, pathogenesis, clinical and
morphological characteristics, stage of development, pulmonary and
extrapulmonary complications, outcomes.
Acute interstitial pneumonitis. Viral and mycoplasma pneumonia. Clinical
and morphological characteristics, outcomes.
Lung abscess. Classification, morphogenesis and pathological, clinical and
morphological characteristics, complications, outcomes. Acute and chronic
abscesses.
Diffuse chronic lung disease. Definition and classification. Chronic
obstructive pulmonary disease. General characteristics.
7. Chronic obstructive pulmonary emphysema - definition, classification,
epidemiology, etiology, patho- and morphogenesis, morphological
characteristics, clinical manifestations, complications, consequences, causes
of death. Other types of emphysema (compensatory, senile, vicarious,
interstitial): clinical and morphological characteristics.
8. Chronic obstructive bronchitis. Definition, classification, etiology,
epidemiology, patho- and morphogenesis, morphological characteristics,
clinical manifestations, complications, outcomes.
9. Bronchiectasis. Definition, etiology, epidemiology, patho- and
morphogenesis, morphological characteristics, clinical manifestations,
complications, outcomes.
10. Diffuse interstitial (infiltrative and restrictive) lung disease. Classification,
clinical and morphological characteristics, pathogenesis. Alveoli.
Morphological characteristics, pathogenesis.
11. Pneumoconiosis (anthracosis, silicosis, asbestosis, berylliosis). Pato, and
morphogenesis, morphological characteristics, clinical manifestations,
complications, causes of death.
12. The tumors of the bronchi and lungs. Epidemiology, principles of
classification. Benign tumors. Malignant tumor. Lung cancer. Bronchogenic
cancer. Epidemiology, etiology, the principles of the International
Classification.
The practical part of the subject:
Slides. In the study micropreparations pay attention to the education elements,
designated by the letters in parentheses.
1. Bronchopneumonia: H & E stain. The light in the mucosa of small bronchi
visible desquamation of the epithelium, edema, hyperemia of the vessels,
inflammatory infiltration, in the lumen of the alveoli accumulation of
leukocytes (a) and peribronchial at adjacent alveoli visible exudate
consisting of desquamated alveolar epithelium, neutrophils, fibrin and
individual erythrocytes (b) surrounding the alveoli are expanded, filled with
air (c).
2. Lobar pneumonia (stage gray hepatization) H & E stain. The visible light
alveolus filled with fibrin, neutrophils, macrophages with hemosiderin (a)
collapse of pulmonary capillaries (b).
3. Carnification lung tissue: H & E stain.
In the lung alveoli are seen filled with granulation or connective tissue (a),
substitute fibrinous exudate. Reason- complication of lobar pneumonia as a
result of the organization of exudate. Exodus - fibrosis, development of
chronic cardiopulmonary failure.
4. Bronchiectasis with symptoms of pulmonary fibrosis. H & E stain. The
area is easily visible lumen of the bronchi, which contains white blood cells,
mucus, fibrin (a), bronchial epithelial sometimes listening, sometimes with
signs of squamous metaplasia (b), the basement membrane of the epithelium
thickened hyalinized (c) in the submucosal layer - sclerosis, diffuse lymphomacrophage infiltration with an admixture of neutrophils (d), mucous glands
in the area of atrophic sclerosis (g).
5. Obstructive emphysema. H & E stain. In visible light gleams respiratory
bronchioles and alveoli extended (a), the alveolar walls are straight, thinned
(b), have the form endplates clavate thickening due to smooth muscle cell
hypertrophy (c), the vessel walls are thickened, sclerotic (g).
macropreparations:
1. Bronchopneumonia: in the lung on the cut seen coalescing airless pockets
of dense granular appearance, is in the center of the small airways in the
lumen of which is determined by the contents of grayish cloudy. The walls
of the larger bronchi thickened, dull grayish gaps in content. Causes:
bacteria, viruses, pathogenic fungi, rarely - protozoa. Complications:
carnification, abscess formation, purulent pleurisy. Outcome: recovery;
unfavorable when abscess pneumonia.
2. Lobar pneumonia (stage gray hepatization): the proportion of light is
increased in size, dense, gray, grainy appearance, with pressure from the cut
surface flows muddy liquid. The pleura dull, covered with a gray-yellow
coating of fibrin. Causes - pneumococci types 1, 2 and 3, at least
diplobatsilla Friedlander (Klebsiella).
Complications: pulmonary - carnification lung - the organization of exudate;
the formation of acute lung abscess or gangrene; empyema; extrapulmonary
to relate to the possibility of infection by lymphogenous and blood ways with lymphogenous generalization there festering mediastenit and
pericarditis, with hematogenous - metastatic abscesses in the brain, purulent
meningitis, severe ulcerative and polypous ulcerative endocarditis, most of
the tricuspid valve, purulent arthritis, peritonitis .
3. Lung abscess: In the middle lobe of the lung cavity is visible rounded with
conspicuous whitish-gray wall in the cavity - a greenish-gray dense content.
In the surrounding lung tissue, there are pockets of coalescing greyish grainy
appearance.
The reason: a complication of acute pneumonia.
4.
5.
6.
7.
8.
Complications and outcomes: the development of a chronic abscess,
empyema, extrapulmonary suppurative complications.
Bronchiectasis: In the fragment lung bronchi greatly expanded in the form
of bags or cylinder walls are thickened, whitish in the gaps defined by the
contents of a thick grayish - pus. The walls of the bronchial tubes protrude
above the surface of the cut in the lung tissue visible thin white layer of
dense tissue, forming a mesh pattern (net diffuse pulmonary fibrosis).
Causes: congenital bronchiectasis, chronic obstructive bronchitis,
bronchopneumonia.
Complications: pulmonary hemorrhage, lung abscess, empyema secondary
AA amyloidosis, brain abscesses.
Outcomes: chronic pulmonary heart disease
Emphysema: lung to increase in size, their edges cover the anterior
mediastinum, swollen, pale pink, soft, do not collapse, cut with a crunch. In
section the bronchial walls do not collapse, sticking out from the surface of
the cut as "chicken feathers" in the lumen of mucopurulent contents.
Peribronchial and perivascular proliferation of connective tissue. Causes:
genetic predisposition, chronic non-specific inflammation in the bronchi and
bronchioles, bronchiectasis, pulmonary fibrosis of various origins, old age.
Complications: the development of hypertension in the pulmonary
circulation and right ventricular hypertrophy - pulmonary heart.
Outcomes: pulmonary heart disease.
Silicosis of the lungs. lobe of the lung is sealed on the visible section thick
blackened scars, scars in the heart of the individual cavities can be seen
arising at the site of the local ischemic necrosis. Around the deformed blood
vessels and bronchi and proliferation of connective tissue. Reason: aspiration
of particles of quartz dust.
Complications often joins tuberculosis.
Outcomes: pulmonary fibrosis, pulmonary heart development.
Peripheric lung cancer. At the top of the unit is easily visible round shape
with sharp edges, the cut gray-white, with hemorrhages and necrosis. The
reasons: the influence of various oncogenic factors. Complications: often the
first clinical signs caused by hematogenous metastasis. The outcome: poor
Central lung cancer. In the left lung root node is visible gray-pink in color,
with no clear contours of the node in the lung tissue strands grow grayish
tissue. Lymph nodes of the root easily increase in size, the cut gray-pink
with a splash of black coal dust. The reasons: the influence of various
oncogenic factors. Complications: atelectasis, pneumonia, tumor lysis with
pulmonary hemorrhage, abscess. Lymphatic and then hematogenous
metastasis. Outcome: unfavorable.
Test control
Select one or more correct answers
1. pneumonia refers to groups
1) dyscirculatory diseases
2) the tumor disease
3) inflammatory diseases
4) processes of disregeneration
5) All the answers are correct
2. For lobar pneumonia is characterized by
1) defeat of an entire lobe or more lung lobes
2) purulent inflammatory exudate
3) fibrinous pleuritis
4) the gradual onset of the disease
5) the primary lesion of the bronchi
3. carnification lungs at lobar pneumonia
1) the manifestation of the disease
2) complication of the disease
3) the outcome of the disease.
4. The stage of development of lobar pneumonia
1) gray hepatization
2) yellow dystrophy
3) mucoid swelling
4) congestion
5) Resolution
6) red hepatization
5. AGENTS lobar pneumonia
1) pneumococcus
2) Staphylococcus aureus
3) Streptococcus
4) virus pneumotropic
5) Klebsiella
6. morphological characters lobar pneumonia AT THE STAGE OF
GREY hepatization
1) fibrin in alveoli
2) the leukocytes and macrophages in the alveolar exudate
3) purulent exudate meltdown
4) edematous fluid in the alveoli
5) collapse of pulmonary capillaries
7. Pulmonary complications of lobar pneumonia
1) Encephalitis
2) carnification
3) lung abscess
4) purulent mediastinitis
5) a pleura empyema
6) gangrene (wet)
8. carnification - IT IS
1) Organization of exudate in the alveoli with the formation of granulation
tissue initially, and then the mature connective tissue
2) excessive activity of leukocytes in the exudate
3) suppuration of exudate
4) bleeding in the exudate
9. CAUSE carnification
1) enhanced fibrinolysis of exudate
2) joining pyogenic flora
3) insufficient fibrinolytic activity of leukocytes
4) the presence of extrapulmonary complications
5) All the answers are correct
6) All the answers are incorrect
10. A characteristic morphological features of focal pneumonia
1) involvement of the pleura
2) acute bronchitis and bronchiolitis
3) necrosis cheesy of exudate
4) fibrinous exudate in the lumen of the alveoli
5) defeat lobe
11. AGENTS interstitial pneumonia
1) Streptococcus
2) pneumococcus
3) Staphylococcus aureus
4) viruses
5) mycoplasma
12. Bronchiectasis - a pathological EXPANSION
1) the lumen of the alveoli
2) one or more of the lumen of the bronchi, comprising cartilaginous plate
and glands with destruction lamina propria and muscularis
3) small bronchi
13. MAIN TYPES of bronchiectasis
1) varicose
2) Cylinder
3) mushroom
4) saccular
5) stellate
14. chronic nonspecific lung diseases
1) pneumonia
2) chronic obstructive pulmonary emphysema
3) chronic bronchitis
4) bronchiectasis
5) brown induration of lungs
15. emphysema may be a manifestation
1) chronic nonspecific pulmonary inflammation
2) age-related processes
3) compensatory and adaptive processes
4) All the answers are correct
5) All the answers are incorrect
16. morphological characters DESTRUCTIVE of bronchiectasis
1) perifocal inflammation
2) stretching acini
3) carnification
4) the gap mezhalveolyarnyh partitions.
17. The changes in the lungs with diffuse chronic bronchitis
1) small focal atelectasis
2) macrofocal sclerosis
3) the formation of destructive bronchiectasis
4) a mesh fibrosis
5) carnification
18. Complications of chronic obstructive bronchitis
1) cardiopulmonary failure
2) pneumonia
3) gangrene
4) pulmonary hemorrhage.
19. CAUSES pneumoconiosis
1) industrial poisons
2) the effect of physical factors
3) Infection
4) industrial dust
20. REASON IS silicosis dust containing
1) silicon dioxide
2) the particles of coal
3) talc
4) silicates
21. obstructive pulmonary disease
1) asthma
2) chronic obstructive bronchitis
3) chronic obstructive pulmonary emphysema
4) bronchiectasis
5) chronic bronchiolitis
22. The most commonly histologic type of central lung cancer
1) adenocarcinoma
2) the bronchioles-alveolar
3) squamous
4) small-cell
5) large cell
23. The most frequently histologic type of peripheral lung cancer
1) adenocarcinoma
2) the bronchioles-alveolar
3) squamous
4) small-cell
5) large cell
24. The important factor for developing chronic bronchitis
1) heart failure
2) Smoking
3) pulmonary hemosiderosis
4) lymphostasis
5) industrial dust
25. ELEMENTS sarcoid granulomas
1) hearth cheesy necrosis
2) Neutrophils
3) CD4 + T lymphocytes
4) fibroblasts
5) epithelioid cells
26. bronchiectasis IT IS
1) expansion of the lumen of the alveoli
2) expansion of the lumen and increase the size of the bronchial glands
3) expansion of the bronchi
4)
retention
cyst
ORENBURG STATE MEDICAL UNIVERSITY
DEPARTMENT OF PATHOLOGICAL ANATOMY
METHODICAL MANUAL FOR PRACTICAL TRAINING FOR STUDENTS OF
FOREIGN FACULTY
THEME:
RENAL DISEASE.
GLOMERULAR DISEASES. GLOMERULONEPHRITIS. TUBULOPATHY.
NEPHROTIC SYNDROME. DISEASES OF THE URINARY SYSTEM AND THE
MALE REPRODUCTIVE SYSTEM.
Glomerulopathy is a group of diseases with a primary lesion of renal glomeruli.
Etiology glomerulopathy divided into primary inflammatory (glomerulonephritis)
and noninflammatory, and secondary.
I. Primary glomerulopathies:
1). Non-inflammatory glomerulopathy:
- The minimum change in the glomeruli (lipoid nephrosis);
- Focal segmental glomerular sclerosis / hyalinosis;
- Membranous glomerulopathy (nephropathy);
- Hereditary nephritis (Alport syndrome);
2). Inflammatory glomerulopathies (glomerulonephritis):
- Acute post-infectious (diffuse proliferative) glomerulonephritis.
- Mesangiocapillary (membranous proliferative) glomerulonephritis.
- Glomerulonephritis with lunate (extracapillary proliferative glomerulonephritis
with antibody to glomerular basement membrane).
II. Secondary glomerulopathy.
- Diabetic glomerulosclerosis,
- Amyloid nephropathy,
-Paraproteinemic
nephropathy
(multiple
macroglobulinemia, cryoglobulinemia)
- Lupus nephropathy,
- Glomerulonephritis in bacterial endocarditis,
- Glomerulonephritis disease Shenlyayna-Henoch.
myeloma,
Waldenstrom's
Glomerulonephritis (inflammatory glomerulopathy) is a group of diseases of
infectious and allergic or undetermined etiology, characterized by bilateral diffuse
or focal not purulent inflammation of the glomerular apparatus of the kidneys with
the development of renal and extrarenal syndrome.
Proliferative glomerulonephritis characterized by an increase in the number of
glomerular cells. Proliferation of endothelial and mesangial cells leads to the
development of intracapillary glomerulonephritis and nephrothelial cell
proliferation (in the cavity of the Bowman’s capsule) leads to extracapillary
glomerulonephritis.
Glomerulonephritis with lunate rapidly progresses within weeks or months, and
leads to irreversible kidney failure. Parietal cell proliferation occurs and migration
of monocytes and macrophages into the space between the capsule and the renal
glomerulus. Lunate is clumps of cells crescent-shaped, obliterating the cavity of
the capsule and compressing the renal glomerulus. Electron microscopy revealed
deposits and breaks the glomerular basement membrane. Membranous
glomerulonephritis characterized by diffuse thickening and doubling the
basement membrane deposition subendothelial, subepithelial and mesangial
deposits (antibodies) and proliferation of mesangial cells (mesangiocapillary).
Non-inflammatory glomerulopathy is almost always accompanied by the
development of nephrotic syndrome, massive daily protenuriey (3,5g),
hypoalbuminemia (less than 3g), generalized edema, and hyperlipidemia. This is a
consequence of increasing the permeability of the glomerular capillary wall for
plasma proteins, associated with damage to the basal membrane by
immunoglobulins and immune complexes. Damage of the basal membrane and
mesangial matrix changes leads to obliteration of the glomerular capillary loops of
the kidney - sclerosis. Sclerosis - increasing the number of homogeneous nonfibrous extracellular matrix (similar in ultrastructure and the chemical composition
of the basement membrane and mesangial matrix) in glomeruli, the accumulation
of collagen types I and III at enlargement of connective tissue in the lunate and the
stroma.
TUBULOPATHY.
I. Noninflammatory tubulopathy.
1. Acute.
Tubulopathy acquired necrotic genesis:
- necrotic nephrosis is necrosis of the tubular epithelium, leading to the
development of acute renal failure. Allocate ischemic tubular necrosis that
develops at shock different etiology or hypohydration and toxic tubular necrosis,
as a result of circulating toxins, endogenous and exogenous origin. Violation of
renal hemodynamic leads to ischemia of the cortex, to dystrophy and necrosis of
the epithelium and to rupture of tubule basement membrane, venous hyperemia of
the medulla, violation of lymphatic drainage, interstitial edema. Changing the
transport function of the tubules, their obstruction by cylinders, as well as
vasoconstriction of afferent arterioles, leading to a decrease in glomerular
filtration rate. Occurs an acute inhibition of kidney function and urination.
2. Chronic.
Hereditary (primary) tubulopathy:
- With polyuria (renal glycosuria, diabetes insipidus, salt diabetes)
- Tubulopathy manifested disease rickets (phosphate diabetes, Debre de ToniFanconi syndrome)
- Tubulopathy with nephrolithiasis and nephrocalcinosis (cystinuria,
hyperoxaluria).
Acquired tubulopathy obstructive genesis:
- Myeloma kidney (nephrosis paraproteinemic). Renal stroma is clogged and
tubule is occlusion by paraprotein, secreting by myeloma cells. Outcomes secondary contracted kidney, amyloidosis, the development of chronic renal
failure.
- Podagric kidney. Its development is associated with increased excretion of uric
acid (giperurikuriya), resulting in damage to the renal parenchyma and the
formation of stones, activate auto-infection and the development of pyelonephritis.
II. Tubulointerstitial nephritis, characterized by inflammatory changes in the
tubules and interstitium. Is classified depending on the cause or nature of the
primary disease. During - acute and chronic. Chronic tubulointerstitial nephritis,
is characterized by diffuse interstitial fibrosis and tubular atrophy with cell
infiltration. The pathogenesis is dominated by immunopathological reaction.
PYELONEPHRITIS
Pyelonephritis is an infectious disease involving an inflammatory process in the
renal pelvis, the cups and the substance of the kidneys, mainly affecting the
interstitial tissue. Acute pyelonephritis is a bacterial infection that enters the
kidney by hematogenous, lymphogenous or ascending ways. For the development
of chronic pyelonephritis in addition to the infection must have vesicoureteral
reflux and obstruction.
Contributing factors: a violation of hygiene, hypothermia, a small length of
urethral, urethral injury catheterization or cystography. Trigger factors of the
ascending pyelonephritis: urinary infection, dyskinesia of renal pelvis or ureter,
vesico – renal and intrarenal reflux, urinary outflow obstruction, abnormalities of
the urinary tract.
Chronic pyelonephritis is characterized by inflammatory and destructive changes
pyelocaliceal system, progressive deformation of the cups and contiguous
parenchyma and asymmetric rough wrinkling with renal sclerosis. There are four
histological stage of the disease.
Stage I - uniform atrophy of the collecting ducts and lymphocytic infiltration
interstitial tissue, glomeruli save. Stage II - part of glomeruli is hyalinized, tubular
atrophy was more pronounced, zones of inflammatory infiltration reduced due to
the substitution of connective tissue, the lumen of the tubules most extended and
filled with the colloidal mass. Stage III - the death and hyalinization of many
glomeruli, urinary tubules are lined with low undifferentiated epithelium and
contain colloidal matter. The microscopic structure of kidney reminiscent thyroid
tissue (thyroid kidney). Stage IV - a sharp reduction in the size of the cortex,
consisting mostly of poor nuclei of connective tissue with abundant lymphocytic
infiltration.
Prostate disease. Malformations - agenesis, hypoplasia, ectopia, extra gland and
true cyst manifest violation of the reproductive and urinary function.
Prostatitis is inflammation of the prostate, nonspecific (bacterial and nonbacterial forms) and specific (syphilis, tuberculosis, fungal infections).
Tumors of the prostate: benign - basal cell and benign prostatic hyperplasia.
Malignant - a cancer (of varying degrees of differentiation and histological
variants):
adenocarcinoma,
squamous
and
adenoskvamozny
cancer
perehodnokletochny, low-grade mucinous carcinoma, signet ring - cell carcinoma
and anaplastic cancer.
CONTROL QUESTIONS
1.
2.
3.
4.
Glomerulardisease. Glomerulonephritis. Сlassification, etiology,
pathogenesis, immunomorphological characteristics.
Acute glomerulonephritis. Post-streptococcal glomerulonephritis and
non streptococcal glomerulonephritis. Rapidly progressive
glomerulonephritis. Etiology, pathogenesis, morphological characteristics
and outcomes.
Chronic glomerulonephritis.Determination, macro- andmicroscopic
characteristics. Uremia. Etiology, pathogenesis,clinical andmorphological
characteristics.
Nephrotic syndrome.Classification. Membranous nephropathy.
Lipoid nephrosis. Focal segmental glomerulosclerosis.
Etiopathogenesis, morphological characteristics. Electron microscopic
differential - diagnostic features. Membranoproliferative
glomerulonephritis. IgA-nephropathy. Focal proliferative and
necrotic glomerulonephritis. Etiopathogenesis, morphological
characteristics.
Glomerular lesions associated with systemic diseases: Systemic lupus
erythematosus. Henoch-Schonlein purpura. Bacterial endocarditis.
Goodpasture's syndrome, essential cryoglobulinemia, plasma
celldyscrasias. Pathogenesis,clinical andmorphological characteristics.
Forecast. Renal amyloidosis. Methods of diagnosis, clinical
manifestations.
6. Hereditary nephritis. Epidemiology, classification, pathogenesis,
morphological characteristics.
7. Kidney disease associated with damage to the tubules and
interstitium. Classification. Acute tubular necrosis(necrotic nephrosis).
Etiology, pathogenesis, morphological characteristics, clinical
manifestations, prognosis.
8. Tubulointerstitial nephritis. Classification, etiology, morphological
characteristics, clinical manifestations, outcome. Tubulointerstitial
nephritis induced by drug sand toxins. Analgesic nephropathy,
pathogenesis, morphological characteristics.
9. Pyelonephritis, and urinary tract infections. Definition, classification.
Etiological and contributing factors, pathways of infection in the kidney.
Acute pyelonephritis. Definition, etiology, contributory diseases and
pathogenesis, morphological characteristics, complications.
10. Chronic
pyelonephritis and reflux nephropathy. Etiology,
pathogenesis,
morphological
variations
and
morphological
characteristics, clinical manifestations, outcomes.
11. Nephrolithiasis. General and local factors playing a role in stone
formation. Patho- and morphogenesis, clinical and morphological
characteristics, outcomes. Urate nephropathy.
12. Tumors
of the kidney. Epidemiology, contributing factors,
classification. Benign tumors: histogenesis, clinical and morphological
characteristics, prognosis. Malignant tumors: renal cell carcinoma,
urothelial carcinoma. Morphological characteristics, especially
metastasis, clinical manifestations, prognosis.
13. Diseases of the prostate gland. Classification. Inflammatory disease.
Prostatitis: acute bacterial, chronic. Etiology, morphogenesis, clinical and
morphological characteristics, complications, outcomes.
14. Benign nodular hyperplasia of the prostate gland. Causes, clinical
manifestations, histological variants, complications and outcomes.
15. Tumors of the prostate gland. Classification. Epidemiology, risk
factors, causes, pathogenesis, and morphogenesis. Prostate cancer,
5.
histological variants, molecular markers, clinical manifestations,
complications, outcomes.
16. Tumors of the urinary bladder. Classification. Morphological
characteristics of benign transitional cell tumors, prognosis. Malignant
epithelial tumors. Epidemiology, risk factors, etiology and
morphogenesis, clinical and morphological characteristics of the different
histological types of cancer, prognosis. Mesenchymal tumor. Secondary
neoplastic lesions.
The practical part of the subject:
Slides: In the study micropreparations pay attention to the education
elements, designated by the letters in parentheses.
1. Necrotic nephrosis. H &E stain.
in theconvoluted tubuleepithelialnecrosis ofthe kidneys(a) and the site of the
destroyedbase membrane (b) are observed. Occlusion of lumenof thedistal
tubule by cylinders (c), with the expressedvascularhyperemiaof medulla(d),
interstitial edema, hemorrhage and accumulation of leukocytes in the dilated
blood vessels (e)
2. Amyloid nephrosis. Stained Congo-Roth. In mesangial glomerular amyloid
brown-red (a), as well as along thebasalmembraneof tubules(b) in the walls
ofarteriolesand(c). The lumen ofthe tubularexpandedpackedcylindersin
theirepithelium ofmanylipids (d). Therediffuse sclerosisof the stromamedulla(d).
3. Intracapillary proliferative glomerulonephritis. H &E stain. Renal
glomerulus is enlarged, anemic (a), there is swelling and proliferation of
endothelial cells and a slight mesangial cell proliferation (b), in a lumen of
capillary loops single neutrophils (c).
4. Chronic nephritis (secondary contracted kidney). H &E stain. The glomeruli
in a state of collapse, replaced by connective tissue or hyaline (a), tubules is
atrophic, epithelium is flattened (b), the walls of the arterioles thickened and
replaced by hyaline, its lumen is significantly narrowed (c). Number of
interstitial connective tissue increased (nephrosclerosis) (d), stored nephrons is
hypertrophied (e).
5. Chronic pyelonephritis. H & E stain.
Most of the tubules is expanded and filled with colloid-cylinder (a), there is a
diffuse interstitial sclerosis cortex and medulla (b), lympho-histiocytic
infiltration with an impurity of neutrophils (c), part of the glomeruli saved with
a marked periglomerular sclerosis (d).
6. Glandular-muscular hypertrophy of the prostate gland. H & E stain.
Adenomere is extended with proliferation of the glandular epithelium and the
formation of papillary structures, directed at glandular cavity (a), the
proliferation of fibromuscular stroma (b), some acini is cystically dilated, lined
by flattened epithelium (c), in the stroma are observed periglandular
lymphohistiocytic infiltrates (d).
Macropreparations:
1. Acute glomerulonephritis.
The kidneys are enlarged, flabby, with a wide full-blooded cortex, which is visible
in the red specks - "motley kidneys".
Reasons: nephritogenic strains of beta-hemolytic streptococcus group A.
Outcome: recovery; transition to chronic glomerulonephritis.
2. Subacute glomerulonephritis with acute exacerbation.
The kidneys are enlarged, pale, flabby consistency, with petechial hemorrhages on
the surface. In the cut cortex dim, yellowish-gray with red specks, sharply
demarcated from dark red pyramid - the "big motley kidney" or "big red kidney".
Reasons: systemic diseases, primary renal lesion (idiopathic and related with
antibody to glomerular basement membrane, or related with immune complexes).
Complications: anuria, pulmonary hemorrhage (Goodpasture's syndrome),
malignant hypertension.
The outcome: the early development of renal failure, secondary contracted kidney.
3. Kidneys with chronic glomerulonephritis (secondary contracted kidney).
The kidneys are symmetrically contracted, dense, gray, fine-grained surface. In the
context of the layers thinned, the boundary between the cortex and medulla is not
expressed. Around the renal pelvis proliferation of adipose tissue.
Reason: terminal stage glomerular inflammatory diseases.
Complications: bleeding in the brain, heart attack.
The outcome: chronic renal failure.
4. Necrotic nephrosis.
The kidney is enlarged, swollen and edematous, fibrous capsule is tense and easily
removed. In the cut a wide cortical substance is anemic, pale gray, separated from
the dark -red pyramids. In the intermediate zone and renal pelvis are observed
hemorrhage.
Reasons: ischemic - a sharp decrease in blood pressure, decrease in blood volume
associated with blood loss or dehydration (prolonged vomiting, profuse diarrhea,
burns, prolonged use of diuretics), renal artery stenosis. Toxic - heavy metals,
drugs, severe infection, massive hemolysis, "crash" syndrome, endogenous
intoxication, snake bites and insect.
Complication: uremic coma.
Outcomes: restoration of the structure and function of the kidneys; acute renal
failure; nephrosclerosis and chronic renal failure.
5. Lipoid nephrosis.
Kidneys greatly enlarged, flabby, the capsule can be easily removed. In a cut wide
kidney bark, pale yellow or pale gray, gray-red pyramid - the "big white kidney".
Cause: unknown, but sometimes develops after a respiratory infection or after
prophylactic immunization.
Outcomes: relatively favorable; nephrotic syndrome.
6. Renal amyloidosis.
The kidneys are increased in size, dense, waxy. In a cut a cortical substance is
wide, matte, and medulla is gray-pink - "big greasy bud" or "large white kidney".
Causes: a) congenital genetic amyloidosis is fermentopathy, b) primary
amyloidosis at myeloma: tumor plasma cells synthesize a low molecular weight
abnormal protein that fills the stroma of the kidneys and leads to atrophy of the
renal parenchyma, c) causes of secondary amyloidosis - chronic infectious disease
with purulent destructive processes and with the disintegration of own tissues, that
leading to a deep intoxication and violation of general protein metabolism. It is a
complication of tuberculosis, chronic suppurative osteomyelitis and bronchiectasis.
Complications: infection (pneumonia, erysipelas, mumps), infarcts, hemorrhage,
cardiac failure.
The outcome: acute or chronic renal failure.
7. Purulent pyelonephritis.
Kidney enlarged, swollen, with hyperemia, thickened capsule is easily removed. On
the surface of the kidney are observed subcapsular small abscesses. In a cut the
renal parenchyma motley - gray and yellow areas of necrosis and suppuration,
hemorrhage. Cavities pelvis and cups expanded, in the its lumen - cloudy urine with
pus. The mucous membrane of the pelvis dim, with foci of hemorrhage, necrosis,
and fibrin gray coating.
Reasons: infection - most commonly E. coli, Proteus, Enterococcus, Streptococcus,
and others.
Complications: carbuncle kidney (at the confluence of major abscesses or
occlusion of large vessels by septic emboli), pyonephrosis (breakthrough of pus
from abscesses in the pelvis), perinephritis and paranephritis (propagation of
purulent process in the capsule and perirenal fat), papillonekrosis (in elderly
diabetics at urinary stasis).
Outcomes: acute renal failure.
8. Kidney stones (nephrolithiasis).
The kidney is enlarged, pale. In a cut the kidney parenchyma is thinned, cups
and pelvis expanded, filled with stones pale yellow, coral-shaped.
Causes 1. General: a violation of mineral metabolism, purine metabolism, diet
(mineral composition of drinking water, the predominance of carbohydrates and
animal protein in the diet) - endemic nephrolithiasis.
2. Local: - dyskinesia of the urinary tract,
- Inflammation of the urinary tract,
- Stagnation of urine.
Complications: hydronephrosis, pyelonephritis, pyonephrosis, urosepsis.
Outcomes: acute and chronic renal failure.
9. Nodular hyperplasia of the prostate gland.
The prostate gland is enlarged, to the greatest degree medium share, who
eminent in the lumen of the urethra and bladder neck. Surface of the gland is
knobby, texture is elastic-dense, nodes is well-demarcated, various sizes,
yellow and pink color. At the cut of gland flow down milky white prostatic
fluid.
Causes associated with a progressive increase in the concentration of serum
17β-estradiol and estrone, formed due to the metabolic conversion from
androstenedione and testosterone in men over 50 years.
Complications: compression and deformation of the urethra and bladder neck,
cystitis, pyelitis, pyelonephritis, hydrouretra, hydronephrosis, obstruction of
urinary outflow, rarely - anuria with the development of acute renal failure.
Outcome: favorable, extremely rare - malignancy.
Test control
Select one or more correct answers
1. Diseases leading to the development of primarily contracted kidney
1) Glomerulonephritis
2) pyelonephritis
3) hypertension
4) Atherosclerosis
2. Outcomes on amyloid nephrosis
1) recovery
2) heart failure
3) uremia
4) death of autoinfection
3. GLOMERULONEPHRITIS CHARACTERISTIC
1) bilateral renal damage
2) the primary lesion glomeruli
3) unilateral renal damage
4) purulent inflammation
5) non purulent inflammation
6) predominant involvement of the interstitial tissue
4. LOCATION IN characteristic changes at the membranous glomerulonephritis
1) proximal tubules
2) the distal tubules
3) the basement membrane of the tubules
4) basement membrane glomerular capillaries
5. Morphological signs of acute nephrosis
1) tubular atrophy
2) hyalinosis glomeruli
3) necrosis of the tubular epithelium
4) the formation of cylinders
6. The disease characterized by the formation of glomerular lunate
1) membranous nephropathy
2) lipoid nephrosis
3) subacute glomerulonephritis
4) acute post-streptococcal glomerulonephritis
7. Macroscopic picture of subacute glomerulonephritis
1) great spotted kidney
2) a large white kidney greasy
3) primary contracted kidney
4) kidney with necrosis papillae of the pyramids
8.POSSIBLE COMPLICATIONS of chronic glomerulonephritis
1) anemia
2) chronic renal failure
3) hyperglycemic coma
4) brain hemorrhage
5) cardiovascular failure
9. CHANGES IN PRODUCTIVITY extracapillary glomerulonephritis
1) protein dystrophy tubular epithelium
2) necrosis of the glomerular capillary loops
3) fibrin in the lumen of the capsule glomerulus
4) proliferation nephrothelial and podocyte to form lunate
5) nodules Kimmelstilya-Wilson
10. Changes arise in the kidney with chronic glomerulonephritis
1) thrombosis, necrosis of the glomerular loops
2) cell proliferation in renal corpuscles
3) glomerular sclerosis and hyalinosis
4) fibrinopurulent hemorrhagic exudate
5) infiltration in the stroma of histiocytes, and plasma cells
11. Macroscopic picture of amyloidosis kidney
1) Great Spotted kidney
2) a large white kidney greasy
3) The big red kidney
4) Kidney with the foci of purulent inflammation
12. The disease with development of secondary nephrotic syndrome
1) renal amyloidosis
2) diabetic nephropathy
3) membranous nephropathy
4) focal segmental glomerular hyalinosis
5) lupus nephritis
13. The outcome in necrotic nephrosis
1) recovery
2) acute renal failure
3) chronic renal failure
4) primary contracted kidney
14. Stages of acute renal failure
1) uremic
2) shock
3) restoration of diuresis
4) nephrotic
5) oligoanuria
15. The disease with development of primary nephrotic syndrome
1) renal amyloidosis
2) diabetic nephropathy
3) membranous nephropathy
4) focal segmental glomerular hyalinosis
5) lupus nephritis
16. SIGNS of the Alport syndrome
1) hereditary disease
2) acquired disease
3) Glomerulopathy
4) tubulointerstinalnoe disease
17. Contributing factors in the development of pyelonephritis
1) obstruction of the urinary tract
2) vesicoureteral reflux
3) hypertension
4) Pregnancy
5) atherosclerosis
6) diabetes
18. Signs of chronic pyelonephritis
1) symmetrically evenly contracted
2) asymmetric uneven contracted
3) lymphohistiocytic infiltration, sclerosis of the stroma and periglomerular
sclerosis
4) cystic tubular atrophy with the advent of lumens in their dense eosinophilic
masses
5) glomerular sclerosis and hyalinosis.
19. Histological forms of the PROSTATE CANCER
1) squamous
2) solid
3) high-grade carcinoma
4) anaplastic carcinoma
5) transitional cell
20. Basic morphological signs of acute pyelonephritis
1) leukocyte infiltration interstitial
2) degenerative changes in tubular epithelium
3) protein cylinders in the tubules
21. GROWTH IN NODES at the nodular prostatic hyperplasia starts at
1) The posterior lobe
2) preprostatic area
3) the prostatic urethra
4) anterior lobe
22. Macroscopic characteristics of nodes at the nodular prostatic hyperplasia
1) Yellow-pink
2) soft consistency
3) foci of hemorrhage on the cut
4) with the cut surface prostatic fluid flow down
23. KIDNEY SYMPTOMS PYELONEPHRITIS
1) oligouriya
2) hematuria
3) leukocyturia
4) bacteriuria
5) dysuria
6) pain
24. The relevant factor in the development of pyelonephritis
1) megauretra
2) stricture of the urethra
3) purulent cystitis
4) chronic tonsillitis
5) sepsis
25. The etiology of acute pyelonephritis
1) immune complexes
2) viruses
3) gram-negative bacteria
4) Gram-positive bacteria
5) hyperoxaluria
26. The conditions that predispose to DEVELOPMENT of nephrolithiasis
1) sickle cell nephropathy
2) hyperparathyroidism
3) gout
4) amyloid nephropathy
5) hyperoxaluria
27 bladder tumors
1) papilloma
2) condyloma
3) adenocarcinoma
4) transitional cell cancer
5) leiomyoma
28. Complications of chronic pyelonephritis
1) perinefrit
2) recovery
3) bleeding in the brain
4) uremia
29. Tubulointerstitial nephritis caused immune disorders and associated with
antibody and glomeruli were observed at
1) syndrome Gudspachera
2) Albright syndrome
3) intoxication
30. Pathological processes in the kidney with acute pyelonephritis
1) serous exudation into the lumen of the glomerular capsule
2) multiple abscesses
3) fibropurulent a pyelitis
4) fibrinous exudate in the lumen of the glomerular
capsule
ORENBURG STATE MEDICAL UNIVERSITY
DEPARTMENT OF PATHOLOGICAL ANATOMY
METHODICAL MANUAL FOR PRACTICAL TRAINING FOR
STUDENTS OF FOREIGN FACULTY
THEME: Anemia. Hemoblastoses.
Anemia is a decrease in hemoglobin concentration per unit volume of
blood below normal. Often accompanied by anemia and decrease the
number of red blood cells.
On the mechanism of the development of the following types of anemia:
1. Anemia due to blood loss (hemorrhagic anemia) associated with
rapid loss of a significant amount of blood (acute) or chronic blood
loss due to pathological processes. Loss of mature erythrocytes
leads to a shift hyperregeneration erythropoiesis. In the liver,
spleen, and blood vessels around the lesions occur extramedullary
hematopoiesis.
2. Anemia associated with impaired production of red blood cells diseritropoetic (megaloblastic, hypoplastic and aplastic).
Causes of secondary diseritropoetic anemias:
a) failure or malabsorption of vitamin B12 and folic acid
(megaloblastic anemia).
b) Violation of hemoglobin synthesis:
- Violation of the synthesis of heme (iron deficiency);
- Breach of iron metabolism (sideroblastic anemia in chronic diseases,
tuberculous lesions of bone marrow);
- Violation of globin synthesis (thalassemia).
3. Anemia due to increased hemolysis - hemolytic anemia occurs due
to destruction of red blood cells.
Among them are:
a) Anemia caused by intra-erythrocytic factors (extravascular
hemolysis).
Hereditary anemia:
- Anemia associated with disruption of the structure plasmolemma
erythrocytes or membranopatii (stomatcytosis, microspherocytosis,
elliptocytosis, violation of the structure of lipid membranes of red
blood cells).
- Anemia caused by deficiency of the enzyme erythrocytes
(fermentopathy).
- Anemia with impaired synthesis of globin (hemoglobinopathies):
a) the carriage of abnormal hemoglobin (HbS, HbC, HbD et al.);
b) a volatile carrier abnormal hemoglobin (globin instability to the
action of oxidizers, heat resulting in amino acid substitutions);
c) thalassemia (imbalance and decreased synthesis of polypeptide
chains).
Acquired anemia:
- Nocturnal hemoglobinuria (somatic mutation of cells - precursors
myelopoiesis).
b) Anemia caused by exo-erythrocytic factors (intravascular
hemolysis).
Autoimmune hemolytic anemia:
a) due to the incomplete and complete thermal antibodies;
b) autoimmune diseases, anemia;
c) other options (idiopathic, drug anemia).
Isoimmune hemolytic anemia:
a) Hemolytic disease of the newborn;
b) transfusion hemolytic reaction.
Mechanical damage of red blood cells:
a) microangiopathic anemia;
b) anemia in pathology or prosthetic heart valves;
c) march hemoglobinuria.
Medicinal immune hemolysis.
Anemia in infectious diseases (malaria).
Anemia caused by hemolytic toxins and substances.
Hypersplenism.
Hemoblastoses - neoplastic diseases of the hematopoietic and
lymphoid tissue, characterized by malignant course. Depending on
the source (bone marrow or organs lymphoreticular system)
hematopoietic tumors of lymphoid tissue and divided into two groups
- the leukemias and lymphomas.
Leukemia - diseases with primary malignant transformation or
pluripotent stem cells directly into the bone marrow.
Leukemic cells haematogenously accommodated in the spleen, liver,
lymph nodes, and then other tissues and organs. In organs affected by
interstitial move around the vessels and their walls are formed
leukemic infiltrates.
According to the degree of differentiation of tumor cells secrete acute
and chronic forms of leukemia.
Lymphoma - monoclonal neoplastic diseases arising from malignant
lymphatic cells of different levels of differentiation before or after
contact with the central authorities lymphopoiesis - thymus, lymph
nodes, spleen. All lymphoma - malignant tumors. The fundamental
difference from leukemia - that malignant transformation of
lymphocytes occurs not in the bone marrow and lymph nodes,
lymphoid organs or tissues but in different organs (such as when the
tumor cells are plasmacytoma of bone). With growth of the tumor
compresses the surrounding tissues, frequent clinical manifestation compartment syndrome (eg, lower or superior vena cava). Tumor
cells in the blood does not circulate. Among lymphoma Hodgkin's
disease and isolated non-Hodgkin's lymphoma. Almost all
lymphomas capable leukemization, but the transformation of
leukemia lymphoma impossible.
Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALLs) are neoplasms composed of
immature B (pre-B) or T (pre-T) cells, which are referred to as
lymphoblasts. About 85% are B-ALLs, which typically manifest as
childhood acute “leukemias.”; The less common T-ALLs tend to present
in adolescent males as thymic “lymphomas.”; There is, however,
considerable overlap in the clinical behavior of B- and T-ALL; for
example, B-ALL uncommonly presents as a mass in the skin or a bone,
and many T-ALLs present with or evolve to a leukemic picture. Because
of their morphologic and clinical similarities, the various forms of ALL
will be considered here together.
ALL is the most common cancer of children. Approximately 2500 new
cases are diagnosed each year in the United States, most occurring in
individuals under 15 years of age. ALL is almost three times as common
in whites as in blacks, and slightly more frequent in boys than in girls.
Hispanics have the highest incidence of any ethnic group. B-ALL peaks
in incidence at about the age of 3, perhaps because the number of normal
bone marrow pre-B cells (the cell of origin) is greatest very early in life.
Similarly the peak incidence of T-ALL is in adolescence, the age when
the thymus reaches its maximal size. B- and T-ALL also occur less
frequently in adults of all ages.
Morphology. In leukemic presentations, the marrow is hypercellular
and packed with lymphoblasts, which replace the normal marrow
elements. Mediastinal thymic masses occur in 50% to 70% of T-ALLs,
which are also more likely to be associated with lymphadenopathy and
splenomegaly. In both B- and T-ALL, the tumor cells have scant
basophilic cytoplasm and nuclei somewhat larger than those of small
lymphocytes. The nuclear chromatin is delicate and finely stippled, and
nucleoli are either absent or inconspicuous. In many cases the nuclear
membrane is deeply subdivided, imparting a convoluted appearance. In
keeping with the aggressive clinical behavior, the mitotic rate is high.
Because of differing responses to chemotherapy, ALL must be
distinguished from acute myeloid leukemia (AML), a neoplasm of
immature myeloid cells that can cause identical signs and symptoms.
Compared with myeloblasts, lymphoblasts have more condensed
chromatin, less conspicuous nucleoli, and smaller amounts of cytoplasm
that usually lacks granules. However, these morphologic distinctions are
not absolute and definitive diagnosis relies on stains performed with
antibodies specific for B- and T-cell antigens. Histochemical stains are
also helpful, in that (in contrast to myeloblasts) lymphoblasts are
myeloperoxidase-negative and often contain periodic acid–Schiffpositive cytoplasmic material.
Clinical Features.
It should be emphasized that although ALL and AML are genetically
and immunophenotypically distinct, they are clinically very similar. In
both, the accumulation of neoplastic “blasts” in the bone marrow
suppresses normal hematopoiesis by physical crowding, competition for
growth factors, and other poorly understood mechanisms. The common
features and those more characteristic of ALL are the following:
•
Abrupt stormy onset within days to a few weeks of the first
symptoms
•
Symptoms related to depression of marrow function, including
fatigue due to anemia; fever, reflecting infections secondary to
neutropenia; and bleeding due to thrombocytopenia
•
Mass effects caused by neoplastic infiltration (which are more
common in ALL), including bone pain resulting from marrow
expansion and infiltration of the subperiosteum; generalized
lymphadenopathy, splenomegaly, and hepatomegaly; testicular
enlargement; and in T-ALL, complications related to compression
of large vessels and airways in the mediastinum
•
Central nervous system manifestations such as headache,
vomiting, and nerve palsies resulting from meningeal spread, all of
which are also more common in ALL
Prognosis.
Pediatric ALL is one of the great success stories of oncology. With
aggressive chemotherapy about 95% of children with ALL obtain a
complete remission, and 75% to 85% are cured. Despite these
achievements, however, ALL remains the leading cause of cancer deaths
in children, and only 35% to 40% of adults are cured. Several factors
have been consistently associated with a worse prognosis: (1) age under
2, largely because of the strong association of infantile ALL with
translocations involving the MLL gene; (2) presentation in adolescence
or adulthood; (3) peripheral blood blast counts greater than 100,000,
which probably reflects a high tumor burden; and (4) the presence of
particular cytogenetic aberrations such as the t(9;22) (the Philadelphia
chromosome). The t(9;22) is present in only 3% of childhood ALL, but
up to 25% of adult cases, which partially explains the poor outcome in
adults. Favorable prognostic markers include (1) an age of 2 to 10 years,
(2) a low white cell count, (3) hyperploidy, (4) trisomy of chromosomes
4, 7, and 10, and (5) the presence of a t(12;21). Notably, the molecular
detection of residual disease after therapy is predictive of a worse
outcome in both B- and T-ALL and is being used to guide new clinical
trials.
Although most chromosomal aberrations in ALL alter the function of
transcription factors, the t(9;22) instead creates a fusion gene that
encodes a constitutively active BCR-ABL tyrosine kinase (described in
more detail under chronic myeloid leukemia). In B-ALL, the BCR-ABL
protein is usually 190 kDa in size and has stronger tyrosine kinase
activity than the form of BCR-ABL that is found in chronic myeloid
leukemia, in which a BCR-ABL protein of 210 kDa in size is usually
seen. Treatment of t(9;22)-positive ALLs with BCR-ABL kinase
inhibitors leads to clinical responses, but patients relapse quickly
because of acquired mutations in BCR-ABL that render the tumor cells
drug-resistant. BCR-ABL-positive B-ALL generates mutations at a high
rate, a phenomenon referred to as genomic instability that contributes to
the clinical progression and therapeutic resistance of many aggressive
malignant tumors.
Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a tumor of hematopoietic progenitors
caused by acquired oncogenic mutations that impede differentiation,
leading to the accumulation of immature myeloid blasts in the marrow.
The arrest in myeloid development leads to marrow failure and
complications related to anemia, thrombocytopenia, and neutropenia.
AML occurs at all ages, but the incidence rises throughout life, peaking
after 60 years of age.
Morphology. The diagnosis of AML is based on the presence of at
least 20% myeloid blasts in the bone marrow. Several types of
myeloid blasts are recognized, and individual tumors may have more
than one type of blast or blasts with hybrid features. Myeloblasts have
delicate nuclear chromatin, two to four nucleoli, and more voluminous
cytoplasm than lymphoblasts. The cytoplasm often contains fine,
peroxidase-positive azurophilic granules. Auer rods, distinctive needlelike azurophilic granules, are present in many cases; they are particularly
numerous in AML with the t(15;17) (acute promyelocytic leukemia).
Monoblasts have folded or lobulated nuclei, lack Auer rods, and are
nonspecific esterase-positive. In some AMLs, blasts show
megakaryocytic differentiation, which is often accompanied by marrow
fibrosis caused by the release of fibrogenic cytokines. Rarely, the blasts
of AML show erythroid differentiation.
The number of leukemic cells in the blood is highly variable. Blasts may
be more than 100,000 per mm3, but are under 10,000 per mm3 in about
50% of patients. Occasionally, blasts are entirely absent from the
blood (aleukemic leukemia). For this reason, a bone marrow
examination is essential to exclude acute leukemia in pancytopenic
patients.
Because it can be difficult to distinguish myeloblasts and lymphoblasts
morphologically, the diagnosis of AML is confirmed by performing
stains for myeloidspecific antigens.
Cytogenetics.
Cytogenetic analysis has a central role in the classification of AML.
Karyotypic aberrations are detected in 50% to 70% of cases with
standard techniques and in approximately 90% of cases using special
high-resolution banding. Particular chromosomal abnormalities correlate
with certain clinical features. AMLs arising de novo in younger adults
are commonly associated with balanced chromosomal translocations,
particularly t(8;21), inv(16), and t(15;17). In contrast, AMLs following
MDS or exposure to DNA-damaging agents (such as chemotherapy or
radiation therapy) often have deletions or monosomies involving
chromosomes 5 and 7 and usually lack chromosomal translocations. The
exception to this rule is AML occurring after treatment with
topoisomerase II inhibitors, which is strongly associated with
translocations involving the MLL gene on chromosome 11q23. AML in
the elderly is also more likely to be associated with “bad” aberrations,
such as deletions of chromosomes 5q and 7q.
Clinical Features.
Most patients present within weeks or a few months of the onset of
symptoms with complaints related to anemia, neutropenia, and
thrombocytopenia, most notably fatigue, fever, and spontaneous
mucosal and cutaneous bleeding. You will remember that these findings
are very similar to those produced by ALL. Thrombocytopenia results in
a bleeding diathesis, which is often prominent. Cutaneous petechiae and
ecchymoses, serosal hemorrhages into the linings of the body cavities
and viscera, and mucosal hemorrhages into the gingivae and urinary
tract are common. Procoagulants and fibrinolytic factors released by
leukemic cells, especially in AML with the t(15;17), exacerbate the
bleeding tendency. Infections are frequent, particularly in the oral cavity,
skin, lungs, kidneys, urinary bladder, and colon, and are often caused by
opportunists such as fungi, Pseudomonas, and commensals.
Signs and symptoms related to involvement of tissues other than the
marrow are usually less striking in AML than in ALL, but tumors with
monocytic differentiation often infiltrate the skin (leukemia cutis) and
the gingiva; this probably reflects the normal tendency of monocytes to
extravasate into tissues. Central nervous system spread is less common
than in ALL. AML occasionally presents as a localized soft-tissue mass
known variously as a myeloblastoma, granulocytic sarcoma, or
chloroma. Without systemic treatment, such tumors inevitably progress
to full-blown AML over time.
Prognosis.
AML is a difficult disease to treat. About 60% of patients achieve
complete remission with chemotherapy, but only 15% to 30% remain
free of disease for 5 years. AMLs with t(8;21) or inv(16) have a
relatively good prognosis with conventional chemotherapy, particularly
in the absence of c-KIT mutations. In contrast, the prognosis is dismal
for AMLs that follow MDS or genotoxic therapy, or that occur in the
elderly, possibly because in these contexts the disease arises out of a
background of hematopoietic stem cell damage or depletion. These
“high-risk” forms of AML (as well as relapsed AML of all types) are
treated with bone marrow transplantation when possible.
It is hoped that new approaches based on a better understanding of
molecular pathogenesis will improve this situation. The best current
example is AML with the t(15;17), which (as we have discussed) is
treated with pharmacologic doses of ATRA combined with conventional
chemotherapy, or, more recently, with arsenic salts, which appear to
cause PML-RARα to be degraded. New therapies that target other
molecular lesions in AML (e.g., the activated FLT3 and c-KIT tyrosine
kinases) are being evaluated.
Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic
Lymphoma (SLL)
These two disorders differ only in the degree of peripheral blood
lymphocytosis. Most affected patients have sufficient lymphocytosis to
fulfill the diagnostic requirement for CLL (absolute lymphocyte count
>4000 per mm3). CLL is the most common leukemia of adults in the
Western world. There are about 15,000 new cases of CLL each year in
the United States. The median age at diagnosis is 60 years, and there is a
2 : 1 male predominance. In contrast, SLL constitutes only 4% of NHLs.
CLL/SLL is much less common in Japan and other Asian countries than
in the West.
Morphology. Lymph nodes are diffusely effaced by an infiltrate of
predominantly small lymphocytes 6 to 12 μm in diameter with round to
slightly irregular nuclei, condensed chromatin, and scant cytoplasm.
Admixed are variable numbers of larger activated lymphocytes that
often gather in loose aggregates referred to as proliferation centers,
which contain mitotically active cells. When present, proliferation
centers are pathognomonic for CLL/SLL. The blood contains large
numbers of small round lymphocytes with scant cytoplasm. Some of
these cells are usually disrupted in the process of making smears,
producing so-called smudge cells. The bone marrow is almost always
involved by interstitial infiltrates or aggregates of tumor cells. Infiltrates
are also virtually always seen in the splenic white and red pulp and the
hepatic portal tracts
Burkitt Lymphoma
Within this category fall (1) African (endemic) Burkitt lymphoma, (2)
sporadic (nonendemic) Burkitt lymphoma, and (3) a subset of aggressive
lymphomas occurring in individuals infected with HIV. Burkitt
lymphomas occurring in each of these settings are histologically
identical but differ in some clinical, genotypic, and virologic
characteristics.
Morphology. Involved tissues are effaced by a diffuse infiltrate of
intermediate-sized lymphoid cells 10 to 25 μm in diameter with round or
oval nuclei, coarse chromatin, several nucleoli, and a moderate amount
of cytoplasm. The tumor exhibits a high mitotic index and contains
numerous apoptotic cells, the nuclear remnants of which are
phagocytosed by interspersed benign macrophages. These phagocytes
have abundant clear cytoplasm, creating a characteristic “starry sky”
pattern. When the bone marrow is involved, aspirates reveal tumor cells
with slightly clumped nuclear chromatin, two to five distinct nucleoli,
and royal blue cytoplasm containing clear cytoplasmic vacuoles.
Clinical Features.
Both endemic and sporadic Burkitt lymphomas are found mainly in
children or young adults; overall, it accounts for about 30% of childhood
NHLs in the United States. Most tumors manifest at extranodal sites.
Endemic Burkitt lymphoma often presents as a mass involving the
mandible and shows an unusual predilection for involvement of
abdominal viscera, particularly the kidneys, ovaries, and adrenal glands.
In contrast, sporadic Burkitt lymphoma most often appears as a mass
involving the ileocecum and peritoneum. Involvement of the bone
marrow and peripheral blood is uncommon, especially in endemic cases.
Burkitt lymphoma is very aggressive but responds well to intensive
chemotherapy. Most children and young adults can be cured. The
outcome is more guarded in older adults.
Multiple Myeloma.
Multiple myeloma is a plasma cell neoplasm characterized by multifocal
involvement of the skeleton. Although bony disease dominates, it can
spread late in its course to lymph nodes and extranodal sites such as the
skin. Multiple myeloma causes 1% of all cancer deaths in Western
countries. Its incidence is higher in men and people of African descent.
It is chiefly a disease of the elderly, with a peak age of incidence of 65
to 70 years.
Morphology. Multiple myeloma usually presents as destructive
plasma cell tumors (plasmacytomas) involving the axial skeleton.
The bones most commonly affected (in descending order of frequency)
are the vertebral column, ribs, skull, pelvis, femur, clavicle, and scapula.
Lesions begin in the medullary cavity, erode cancellous bone, and
progressively destroy the bony cortex, often leading to pathologic
fractures; these are most common in the vertebral column, but may
occur in any affected bone. The bone lesions appear radiographically
as punched-out defects, usually 1 to 4 cm in diameter, and grossly
consist of soft, gelatinous, red tumor masses. Less commonly,
widespread myelomatous bone disease produces diffuse
demineralization (osteopenia) rather than focal defects.
Even away from overt tumor masses, the marrow contains an increased
number of plasma cells, which usually constitute more than 30% of the
cellularity. The plasma cells may infiltrate the interstitium or be present
in sheets that completely replace normal elements. Like their benign
counterparts, malignant plasma cells have a perinuclear clearing due to a
prominent Golgi apparatus and an eccentrically placed nucleus.
Relatively normal-appearing plasma cells, plasmablasts with vesicular
nuclear chromatin and a prominent single nucleolus, or bizarre,
multinucleated cells may predominate. Other cytologic variants stem
from the dysregulated synthesis and secretion of Ig, which often leads to
intracellular accumulation of intact or partially degraded protein. Such
variants include flame cells with fiery red cytoplasm, Mott cells with
multiple grapelike cytoplasmic droplets, and cells containing a variety of
other inclusions, including fibrils, crystalline rods, and globules. The
globular inclusions are referred to as Russell bodies (if cytoplasmic) or
Dutcher bodies (if nuclear). In advanced disease, plasma cell infiltrates
may be present in the spleen, liver, kidneys, lungs, lymph nodes, and
other soft tissues.
Commonly, the high level of M proteins causes red cells in peripheral
blood smears to stick to one another in linear arrays, a finding referred to
as rouleaux formation. Rouleaux formation is characteristic but not
specific, in that it may be seen in other conditions in which Ig levels are
elevated, such as lupus erythematosus and early HIV infection. Rarely,
tumor cells flood the peripheral blood, giving rise to plasma cell
leukemia. Bence Jones proteins are excreted in the kidney and
contribute to a form of renal disease called myeloma kidney.
Hodgkin Lymphoma (lymphogranulomatosis)
Hodgkin lymphoma (HL) encompasses a group of lymphoid neoplasms
that differ from NHL in several respects. While NHLs frequently occur
at extranodal sites and spread in an unpredictable fashion, HL arises in a
single node or chain of nodes and spreads first to anatomically
contiguous lymphoid tissues. For this reason, the staging of HL is much
more important in guiding therapy than it is in NHL. HL also has
distinctive morphologic features. It is characterized by the presence of
neoplastic giant cells called Reed-Sternberg cells. These cells release
factors that induce the accumulation of reactive lymphocytes,
macrophages, and granulocytes, which typically make up greater than
90% of the tumor cellularity. In the vast majority of HLs, the neoplastic
Reed-Sternberg cells are derived from germinal center or post-germinal
center B cells.
Differences between Hodgkin and Non-Hodgkin Lymphomas
Hodgkin Lymphoma
Non-Hodgkin Lymphoma
More often localized to a single axial
group of nodes (cervical, mediastinal,
para-aortic)
More frequent involvement of
multiple peripheral nodes
Orderly spread by contiguity
Noncontiguous spread
Mesenteric nodes and Waldeyer ring
rarely involved
Waldeyer ring and mesenteric
nodes commonly involved
Extra-nodal presentation rare
Extra-nodal presentation
common
Hodgkin lymphoma accounts for 0.7% of all new cancers in the United
States; there are about 8000 new cases each year. The average age at
diagnosis is 32 years. It is one of the most common cancers of young
adults and adolescents, but also occurs in the aged. It was the first
human cancer to be successfully treated with radiation therapy and
chemotherapy, and is curable in most cases.
Classification.
The WHO classification recognizes five subtypes of HL:
1.
Nodular sclerosis
2.
Mixed cellularity
3.
Lymphocyte-rich
4.
Lymphocyte depletion
5.
Lymphocyte predominance
In the first four subtypes—nodular sclerosis, mixed cellularity,
lymphocyte-rich, and lymphocyte depletion—the Reed-Sternberg cells
have a similar immunophenotype. These subtypes are often lumped
together as classical forms of HL. In the remaining subtype, lymphocyte
predominance, the Reed-Sternberg cells have a distinctive B-cell
immunophenotype that differs from that of the “classical” types.
Subtypes of Hodgkin Lymphoma
Morphology and
Subtype
Immunophenotype
Typical Clinical Features
Nodular
sclerosis
Frequent lacunar cells and
occasional diagnostic RS cells;
background infiltrate composed of
T lymphocytes, eosinophils,
macrophages, and plasma cells;
fibrous bands dividing cellular areas
into nodules. RS cells CD15+,
CD30+; usually EBV-
Most common subtype;
usually stage I or II disease;
frequent mediastinal
involvement; equal
occurrence in males and
females (F = M), most
patients young adults
Mixed
cellularity
Frequent mononuclear and
diagnostic RS cells; background
infiltrate rich in T lymphocytes,
eosinophils, macrophages, plasma
cells; RS cells CD15+, CD30+;
70% EBV+
More than 50% present as
stage III or IV disease; M
greater than F; biphasic
incidence, peaking in young
adults and again in adults
older than 55
Lymphocyte
rich
Frequent mononuclear and
Uncommon; M greater than
diagnostic RS cells; background
F; tends to be seen in older
infiltrate rich in T lymphocytes; RS adults
cells CD15+, CD30+; 40% EBV+
Lymphocyte
depletion
Reticular variant: Frequent
diagnostic RS cells and variants and
a paucity of background reactive
cells; RS cells CD15+, CD30+;
most EBV+
Lymphocyte Frequent L&H (popcorn cell)
predominance variants in a background of
follicular dendritic cells and
reactive B cells; RS cells CD20+,
CD15-, C30-; EBV-
Uncommon; more common
in older males, HIV-infected
individuals, and in
developing countries; often
presents with advanced
disease
Uncommon; young males
with cervical or axillary
lymphadenopathy;
mediastinal
L&H, lymphohistiocytic; RS cell, Reed-Sternberg cell.
Clinical Staging of Hodgkin and Non-Hodgkin Lymphomas (Ann
Arbor Classification)
Stage Distribution of Disease
I
Involvement of a single lymph node region (I) or a single extralymphatic organ or site (IE).
II
Involvement of two or more lymph node regions on the same
side of the diaphragm alone (II) or localized involvement of an
extra-lymphatic organ or site (IIE).
III
Involvement of lymph node regions on both sides of the
diaphragm without (III) or with (IIIE) localized involvement of
an extra-lymphatic organ or site.
IV
Diffuse involvement of one or more extra-lymphatic organs or
sites with or without lymphatic involvement.
All stages are further divided on the basis of the absence (A) or presence
(B) of the following symptoms: unexplained fever, drenching night
sweats, and/or unexplained weight loss of greater than 10% of normal
body weight.
The practical part
micropreparations:
1. The liver in chronic myeloid leukemia. H & E stain.
The liver lobules in the course of a marked infiltration of the sinusoids
leukemia cells of the myeloid series (a) and a small tumor infiltration of
myelocytes portal tracts (b), in a state of hepatocytes steatosis (c),
observed their lipofusinoz (g).
2. The liver in chronic lymphocytic leukemia. H & E stain.
In the course of the capsule and portal tracts massive clusters of tumor
cells of lymphoid series (a) in hepatocytes marked protein and fatty
degeneration (b) lipofuscinosis (c).
3. Hodgkin Lymphoma lymph node (Mixed cellularity type.). H &
E stain.
In the lymph node tissue the expressed cellular polymorphism: visible
large mononuclear cells Hodgkin (a) multinucleated Reed - Sternberg
cells (b), the lymphocytes (B), plasma cells (g), eosinophils (d),
neutrophils (e). Determined nodules undergoing necrosis and sclerosis
(g).
macropreparations:
1. The liver in chronic lymphocytic leukemia.
The liver is enlarged in size, dense consistency, light brown color on the
surface and cross-section are seen small gray-white nodules.
Causes hematogenous metastasis of leukemic cells from the bone
marrow.
The outcome: adverse, liver failure.
2. necrotic angina at acute leukemia.
The tonsils are enlarged, on the surface and in the depths of visible areas
of coagulation necrosis and ulceration of gray-black. Tissue around the
tonsils is hydropic, hyperemic. In the mucosa of tongue and throat
diapedetic it has many small and larger hemorrhages.
Reasons: leukemic infiltration of lymphoid tissue.
Complications: bleeding, infection joining.
3. The lymph nodes in chronic lymphocytic leukemia.
Lymph nodes were increased, merge into a huge plotnovata packages,
the boundary between them is preserved in some places, but the capsule
is soldered to the surrounding tissue. On a section of the fabric uniform,
juicy, white and pink.
Reasons: leukemic infiltration of the lymph nodes, leading to a sharp
disruption of their structure and the surrounding tissue.
Complications: compression of the adjacent organs.
Outcome: necrosis adhesions.
4. The spleen in chronic myeloid leukemia.
The spleen is greatly increased in size, weighing about 3 kg, dense,
smooth capsule, speckled appearance. In the context of the parenchyma
dark red color, with white foci of ischemic infarcts.
Reasons: diffuse leukemic infiltration, occlusion of blood vessels of the
spleen tumor cells.
Complications: rupture of the capsule and parenchymal bleeding.
The outcome: poor: dysfunction of the spleen.
5. The bone marrow in chronic myeloid leukemia. Bone marrow
epiphyseal and diaphyseal long bones replaced by lush gray-pink or
greenish tissue grows into the medullary canal ("pyoid " bone marrow).
Reasons: replacement of normal bone marrow tumor tissue.
The outcome: the suppression of hematopoiesis, anemia, opportunistic
infections.
6. The spleen in the lymphogranulomatosis.
Spleen increased in size, the cut red-brown organ parenchyma replaced
by yellow-white tumor tissue, forming pockets of irregular shape, or
growths with foci of necrosis and sclerosis ("porphyry" spleen).
The reasons: generalized cancer.
Outcome: dysfunction of the spleen.
Test control
Select one or more correct answers
1. Signs of acute lymphoblastic leukemia
1) The peak incidence at age 60
2) develops mainly in children
3) the prevalence of lymphoblasts in the bone marrow and blood
4) struck lymph nodes
5) in the leukemic infiltrates predominate myeloblasts
2. Clue cells in lymphoid tissues IN lymphogranulomatosis
1) cells Anichkova
2) cells of Hodgkin
3) cells Mikulic
4) cells Reed-Sternberg
3. Morphological changes lymph nodes in lymphogranulomatosis
1) amyloid deposition in the stroma
2) numerous cells Reed-Sternberg
3) cells of Hodgkin
4) necrosis, sclerosis
5) hyperplasia bright centers of follicles
4. Characteristic signs of chronic myeloid leukemia
1) pyoid bone marrow
2) axillary resorption and osteoporosis
3) intralobular leukemic infiltration of the liver
4) infiltration of the portal stroma leukemia cells
5) aleukemic leukemia
5. Bence-Jones protein was detected in the urine at
1) chlamydia
2) Multiple Myeloma
3) chronic myeloid leukemia
4) chronic lymphocytic leukemia
6. spleen weight increase greatly the in leukemia
1) acute
2) chronic
7. The features typical of Burkitt's lymphoma
1) a high degree of malignancy
2) is more common in people of Europe
3) the picture "starry sky"
4) marked cellular polymorphism of tumor tissue
5) detection of tumor cells virus Epstein – Bar
8. TYPE lymphogranulomatosis with the most unfavorable
prognosis
1) predominance of lymphoid tissue
2) mixed cell
3) nodular sclerosis
4) Lymphocyte depletion
5) lymphohistiocytic
9. Do not look at treatment with cytostatics leukemic infiltrates
STORED IN
1) heart
2) Kidney
3) brain
4) spleen
10. Anemia characterizes
1) reduction in the number of red blood cells
2) an increase in hemoglobin in the blood
3) decrease in circulating blood volume
4) decrease in hemoglobin, and often in the number of erythrocytes per
unit volume of blood
11. BONE MARROW strikes PRIMARY
1) malignant lymphoma
2) in leukemia
12. Bone marrow involvement lymphoma
1) secondary to metastatic
2) primary
13. Causes of nutritional iron deficiency anemia
1) Gastrectomy
2) Pregnancy
3) autoimmune gastritis
14. The cause of iron deficiency anemia in pregnant and nursing
mothers
1) lack of receipt of exogenous iron
2) lack of synthesis of endogenous iron
15. CAUSE hemolytic anemia
1) lack factor Castle
2) incompatible blood transfusion
16. In chronic leukemia is more characteristic
1) The proliferation of undifferentiated (blast) cells
2) the proliferation of ripening (cytic) cells
17. The forms of leukemia in children, with a favorable prognosis
1) T-lymphoblastic
2) B-lymphoblastic
3) myeloblastic
4) undifferentiated
5) plazmoblastic
ORENBURG STATE MEDICAL UNIVERSITY
DEPARTMENT OF PATHOLOGICAL ANATOMY
METHODICAL MANUAL FOR PRACTICAL TRAINING FOR
STUDENTS OF FOREIGN FACULTY
THEME: DISEASES OF THE CARDIOVASCULAR SYSTEM
Atherosclerosis and arteriosclerosis. Hypertension and arteriolosclerosis.
Hypertensive heart disease. Myocardial hypertrophy.
Arteriosclerosis
Arteriosclerosis literally means “hardening of the arteries”; it is a generic term
reflecting arterial wall thickening and loss of elasticity. There are three general
patterns, with differing clinical and pathologic consequences:
• Arteriolosclerosis affects small arteries and arterioles, and may cause
downstream ischemic injury. The anatomic variants, hyaline and
hyperplastic, were discussed above in relation to hypertension.
•
Mönckeberg medial sclerosis is characterized by calcific deposits in
muscular arteries in persons typically older than age 50. The deposits may
undergo metaplastic change into bone. Nevertheless, the lesions do not
encroach on the vessel lumen and are usually not clinically significant.
•
Atherosclerosis, from Greek root words for “gruel” and “hardening,” is the
most frequent and clinically important pattern and will now be discussed in
detail.
Atherosclerosis is a chronic disease resulting from disorders of lipid and protein
metabolism, with the defeat of the arteries elastic and muscular-elastic types in the
form of focal deposits in the intima of lipids and proteins with the growth of
connective tissue. Morphological substrate of atherosclerosis is atherosclerotic
plaque narrows lumen of the artery.
Etiology: polietiologic disease caused by a combination of disorders of lipid and
protein metabolism to damage the endothelium of the arteries.
Risk factors for atherosclerosis: hyperlipidemia, hypertension, heredity, smoking,
age, sex, hormonal factors, stress, obesity, lack of exercise, viruses.
With this overview of pathogenesis, we will now discuss the morphologic features
and evolution of atherosclerosis.
morphological stage
Fatty Streaks. Fatty streaks are the earliest lesions in atherosclerosis. They are
composed of lipid-filled foamy macrophages. Beginning as multiple minute flat
yellow spots, they eventually coalesce into elongated streaks 1 cm or more in
length. These lesions are not significantly raised and do not cause any flow
disturbance. Aortas of infants less than 1 year old can exhibit fatty streaks, and
such lesions are seen in virtually all children older than 10 years, regardless of
geography, race, sex, or environment. The relationship of fatty streaks to
atherosclerotic plaques is uncertain; although they may evolve into precursors of
plaques, not all fatty streaks are destined to become advanced lesions.
Nevertheless, coronary fatty streaks begin to form in adolescence, at the same
anatomic sites that later tend to develop plaques.
Atherosclerotic Plaque. The key processes in atherosclerosis are intimal
thickening and lipid accumulation. Atheromatous plaques impinge on the lumen of
the artery and grossly appear white to yellow; superimposed thrombus over
ulcerated plaques is red-brown. Plaques vary from 0.3 to 1.5 cm in diameter but
can coalesce to form larger masses.
Atherosclerotic lesions are patchy, usually involving only a portion of any given
arterial wall, and are rarely circumferential; on cross-section, the lesions therefore
appear “eccentric”. The focality of atherosclerotic lesions—despite the uniform
exposure of vessel walls to such factors as cigarette smoke toxins, elevated lowdensity lipoprotein (LDL), hyperglycemia, etc.—is attributable to the vagaries of
vascular hemodynamics. Local flow disturbances (e.g., turbulence at branch
points) leads to increased susceptibility of certain portions of a vessel wall to
plaque formation. Though focal and sparsely distributed at first, atherosclerotic
lesions can become more numerous and more diffuse with time.
In humans, the abdominal aorta is typically involved to a much greater degree than
the thoracic aorta. In descending order, the most extensively involved vessels are
the lower abdominal aorta, the coronary arteries, the popliteal arteries, the internal
carotid arteries, and the vessels of the circle of Willis. Vessels of the upper
extremities are usually spared, as are the mesenteric and renal arteries, except at
their ostia. Nevertheless, in an individual case, the severity of atherosclerosis in
one artery does not predict its severity in another. Moreover, in any given vessel,
lesions at various stages often coexist.
Atherosclerotic plaques have three principal components: (1) cells, including
smooth muscle cells, macrophages, and T cells; (2) ECM, including collagen,
elastic fibers, and proteoglycans; and (3) intracellular and extracellular lipid.
These components occur in varying proportions and configurations in different
lesions. Typically, there is a superficial fibrous cap composed of smooth muscle
cells and relatively dense collagen. Beneath and to the side of the cap (the
“shoulder”) is a more cellular area containing macrophages, T cells, and smooth
muscle cells. Deep to the fibrous cap is a necrotic core, containing lipid (primarily
cholesterol and cholesterol esters), debris from dead cells, foam cells (lipid-laden
macrophages and smooth muscle cells), fibrin, variably organized thrombus, and
other plasma proteins; the cholesterol is frequently present as crystalline
aggregates that are washed out during routine tissue processing and leave behind
only empty “clefts.” The periphery of the lesions show neovascularization
(proliferating small blood vessels. Typical atheromas contain abundant lipid, but
some plaques (“fibrous plaques”) are composed almost exclusively of smooth
muscle cells and fibrous tissue.
Plaques generally continue to change and progressively enlarge due to cell death
and degeneration, synthesis and degradation (remodeling) of extracellular matrix
(ECM), and organization of thrombus. Moreover, atheromas often undergo
calcification.
Atherosclerotic plaques are susceptible to the following clinically important
changes (see also subsequent discussion):
• Rupture, ulceration, or erosion of the intimal surface of atheromatous
plaques exposes the blood to highly thrombogenic substances and induces
thrombosis. Such thrombosis can partially or completely occlude the lumen
and lead to downstream ischemia. If the patient survives the initial
thrombotic occlusion, the clot may become organized and incorporated into
the growing plaque.
•
Hemorrhage into a plaque. Rupture of the overlying fibrous cap, or of the
thin-walled vessels in the areas of neovascularization, can cause intra-plaque
hemorrhage; a contained hematoma may expand the plaque or induce plaque
rupture.
•
Atheroembolism. Plaque rupture can discharge atherosclerotic debris into
the bloodstream, producing microemboli.
•
Aneurysm formation. Atherosclerosis-induced pressure or ischemic
atrophy of the underlying media, with loss of elastic tissue, causes weakness
resulting in aneurysmal dilation and potential rupture (see below).
Clinical and morphological forms:
1. Atherosclerosis of the aorta. Allocate syndrome and aortic arch syndrome
Leriche.
2. Atherosclerosis of coronary arteries leads to the development of coronary heart
disease.
3. Atherosclerosis cerebral arteries underlies cerebrovascular diseases.
4. Atherosclerosis of renal artery. Partial obstruction atherosclerotic plaque
clearance renal artery leads to atrophy and sclerosis of the renal parenchyma and
the development of primary contracted kidney (atherosclerotic renal scarring).
Renal artery thrombosis developing ischemic infarction.
5. Atherosclerosis mesenteric arteries leading to the development of ischemic
colitis in the case of chronic heart failure. With complete occlusion of the artery by
a thrombus or embolus, bowel gangrene develops.
6. Atherosclerosis of the arteries of the lower extremities. Most affected femoral
artery. Chronic heart failure leads to atrophy and sclerosis of tissues. Arterial
thrombosis leading to gangrene.
Hypertensive Vascular Disease (essential hypertension) - a disease manifested by
an increase in blood pressure above 140/90 mm Hg. Art.
Risk factors: genetic predisposition, chronic psychoemotional voltage, excessive
salt intake, physical inactivity, obesity, smoking, hormonal disorders, alcohol
abuse.
Pathogenesis: the basis for the development of hypertension is a violation of the
regulation of vascular tone caused by defects of pressor and depressor mechanisms
underlying the normal pressure, genetically determined defect in renal volume
regulation mechanism of AD and inherited defect of cell membranes, including
smooth muscle cells, which leads to excess in they Ca and Na and causes their
spasm.
Morphological substrate of essential hypertension is a muscle spasm in the small
arteries and arterioles. Major structural changes occurring in the vessels:
hyperplasia and hypertrophy of smooth muscle cells, hyalinosis, multiple sclerosis,
which leads to thickening of the wall and narrowing of the lumen.
Benign form is characterized by a gradual increase in blood pressure in the vessels
and staging of the disease.
1.
Transient stage (pre-clinical) morphologically characterized by spasm of the
arterioles, plasmorrhages, smooth muscle cell hyperplasia, hypertrophy and
giperelastozom artery walls. The walls of the left ventricle in response to a periodic
increase in peripheral resistance, compensatory hypertrophy.
2.
Vascular stage. Microangiopathy most characteristic feature of hypertension.
Characterized hyalinosis arteriolosclerosis and developing in all organs, but is most
pronounced in arterioles of the kidneys, brain, pancreas and retina.
Macroangiopathy are structural changes in large and medium arteries of the
development of elastofibrosis in the walls, collagen and elastin substitution
atherosclerosis. The process involves the blood vessels elastic and muscular-elastic
type. Fibrotic plaques circularly arranged and sharply narrow the lumen of blood
vessels. Increases myocardial hypertrophy ("bovine heart"), with the progression of
coronary insufficiency develops degeneration and death of muscle cells, intramural
change elements of the nervous system, cardio and myogenic dilatation of the heart
cavities.
3.
Organ stage is associated with impaired circulation intraorganic due to
hyalinosis and atherosclerosis. With a slow progression failure intraorganic flow,
develop atrophic and sclerotic processes. As a result of acute spasm artery
thrombosis or fibrinoid necrosis of its wall for hypertensive crisis, in the tissues of
heart attacks and possible hemorrhage.
Malignant form - frequent and repeated crises with diastolic blood pressure higher
than 120 mmHg Morphologically, it is characterized by arteriolar fibrinoid
necrosis, thrombosis, with the development of heart attacks and hemorrhages.
Mainly affects the kidneys. This malignant nephrosclerosis Farah.
Clinical and morphological forms of hypertension:
1. The brain form is the basis of group of cerebrovascular diseases.
2. The heart Form is the basis of coronary heart disease.
3. Renal form leads to the development of primary contracted kidney with the
development of chronic renal failure and uremia azotemicheskoy.
4. Hypertensive retinopathy is characterized by retinal hyalinosis vessels, leading
to retinal hemorrhages and focal its detachment.
SECONDARY HYPERTENSION
Renal
Acute glomerulonephritis
Chronic renal disease
Polycystic disease
Renal artery stenosis
Renal vasculitis
Renin-producing tumors
Endocrine
Adrenocortical hyperfunction (Cushing syndrome, primary aldosteronism,
congenital adrenal hyperplasia, licorice ingestion)
Exogenous hormones (glucocorticoids, estrogen [including pregnancyinduced and oral contraceptives], sympathomimetics and tyraminecontaining foods, monoamine oxidase inhibitors)
Pheochromocytoma
Acromegaly
Hypothyroidism (myxedema)
Hyperthyroidism (thyrotoxicosis)
Pregnancy-induced
Cardiovascular
Coarctation of aorta
Polyarteritis nodosa
Increased intravascular volume
Increased cardiac output
Rigidity of the aorta
Neurologic
Psychogenic
Increased intracranial pressure
Sleep apnea
Acute stress, including surgery
Ischemic heart disease (IHD) - a group of diseases caused by absolute or relative
deficiency of the coronary circulation, which manifests imbalance between
myocardial oxygen demand and delivery.
Coronary heart disease is a cardiac Form of atherosclerosis and hypertension.
Risk Factors of I order:
-giperlipidemiya (hypercholesterolemia); hypertension;
-kurenie, sedentary lifestyle, male.
Risk Factors II order:
-tuchnost; stress; metabolic disorders; deficiency of magnesium and selenium;
hypercalcemia; hyperfibrinogenemia.
forms of acute ischemic heart disease:
1.
Sudden cardiac death - death due to cardiac arrest in humans, for 6 hours
before who had a satisfactory condition and do not complain of cardiovascular
nature. Causes - a spasm of the coronary arteries, they rarely thrombosis.
Myocardial ischemia can last up to 6 hours. Morphological substrate of sudden
coronary death ischemic myocardium dystrophy. Acute myocardial ischemia
promotes the formation of arrhythmogenic substances sympathoadrenal system
activation and increased concentrations of epinephrine, which leads to electrical
instability of the myocardium. When restoring blood flow in the ischemic area of
the myocardium, the blood is leaching from ischemia zone arrhythmogenic agents
which damage cardiomyocytes functioning myocardium (reperfusion effect),
causing it to electrical instability and ventricular fibrillation.
2.
Angina pectoris (literally, chest pain) is characterized by paroxysmal and
usually recurrent attacks of substernal or precordial chest discomfort (variously
described as constricting, squeezing, choking, or knifelike) caused by transient (15
seconds to 15 minutes) myocardial ischemia that falls short of inducing.
Morphological expression of angina pectoris - ischemic myocardial degeneration,
leading to diffuse small-focal cardiosclerosis.
The three overlapping patterns of angina pectoris—(1) stable or typical angina, (2)
Prinzmetal variant angina, and (3) unstable or crescendo angina—are caused by
varying combinations of increased myocardial demand, decreased myocardial
perfusion, and coronary arterial pathology. Moreover, not all ischemic events are
perceived by patients (silent ischemia).
Stable angina, the most common form, is also called typical angina pectoris. It is
caused by an imbalance in coronary perfusion (due to chronic stenosing coronary
atherosclerosis) relative to myocardial demand, such as that produced by physical
activity, emotional excitement, or any other cause of increased cardiac workload.
Typical angina pectoris is usually relieved by rest (which decreases demand) or
administering nitroglycerin, a strong vasodilator (which increases perfusion).
Prinzmetal variant angina is an uncommon from of episodic myocardial ischemia
that is caused by coronary artery spasm. Although individuals with Prinzmetal
variant angina may well have significant coronary atherosclerosis, the anginal
attacks are unrelated to physical activity, heart rate, or blood pressure. Prinzmetal
angina generally responds promptly to vasodilators, such as nitroglycerin and
calcium channel blockers.
Unstable or crescendo angina refers to a pattern of increasingly frequent pain,
often of prolonged duration, that is precipitated by progressively lower levels of
physical activity or that even occurs at rest. In most patients, unstable angina is
caused by the disruption of an atherosclerotic plaque with superimposed partial
(mural) thrombosis and possibly embolization or vasospasm (or both). Unstable
angina thus serves as a warning that an acute MI may be imminent; indeed, this
syndrome is sometimes referred to as preinfarction angina.
3.
Myocardial infarction - circulatory myocardial necrosis occurring due to
acute failure of the absolute coronary flow.
Reasons. Thrombosis, prolonged spasm, thrombosis, myocardial functional
overvoltage conditions arteriosclerotic occlusion and collateral circulation failure.
Classification.
At the time of occurrence:
- Primary (acute) myocardial infarction within 4 weeks of ischemic stroke prior to
the formation of the scar;
- Repeated myocardial infarction (4 weeks or more after the initial heart attack);
- Recurrent myocardial infarction occurring within 4 weeks of the existence of a
primary or recurrent heart attack).
Localization:
Anterior myocardial infarction occurs when blood flow disturbance in the left
coronary artery, and its descending branch,
Posterior myocardial infarction occurs when occlusion of the circumflex branch,
An extensive myocardial infarction, occlusion of the left main coronary artery,
Myocardial infarction of the right ventricle.
Stages of myocardial infarction:
1.
Ischemic stage lasting 18-24 hours. Macroscopic signs of ischemia of the
heart muscle - the myocardium with a flabby moderately uneven hyperemia.
Special sample and reaction test with potassium tellurite, reaction with nitro-ST,
fluorescent microscopy, polarization microscopy. Microscopic through in the
ischemic area of microcirculation disorders, uneven contraction and relaxation of
myofibrils, their vacuolar and fatty degeneration, swelling of the stroma.
2.
Necrotic stage - ischemic (White) coagulation necrosis with hemorrhagic
aureole. Within 2 weeks of going miomalyatsiya and muscle tissue resorption. By
the beginning of two weeks begins to form granulation tissue. In cardiomyocytes
functioning myocardium in this period is preserved myocardial hypertrophy.
3.
The stage scarring. At 3 weeks of almost the whole area of necrosis replaced
maturing granulation to 4-6 weeks they become mature connective tissue.
Adapting to the new conditions of the heart operation is completed in 2-2.5
months. Hypertrophy of muscle tissue will progress until, until the mixture does
not provide adequate myocardial contractility.
Evolution of Morphologic Changes in Myocardial Infarction
Time Gross Features
Light Microscope
Electron
Microscope
REVERSIBLE INJURY
0–½
hr
None
None
Ralaxation of
myofibrils;
glycogen loss;
mitochondrial
swelling
IRREVERSIBLE INJURY
½–4
hr
None
Usually none; variable waviness
of fibers at border
4–12 Dark mottling
hr
(occasional)
Early coagulation necrosis;
edema; hemorrhage
12– Dark mottling
24 hr
Ongoing coagulation necrosis;
pyknosis of nuclei; myocyte
hypereosinophilia; marginal
contraction band necrosis; early
neutrophilic infiltrate
1–3
days
Mottling with
Coagulation necrosis, with loss of
yellow-tan infarct nuclei and striations; brisk
center
interstitial infiltrate of neutrophils
3–7
days
Hyperemic
border; central
yellow-tan
softening
Beginning disintegration of dead
myofibers, with dying
neutrophils; early phagocytosis of
dead cells by macrophages at
infarct border
7–10 Maximally
days yellow-tan and
soft, with
depressed red-tan
margins
Well-developed phagocytosis of
dead cells; early formation of
fibrovascular granulation tissue at
margins
10–
14
days
Red-gray
depressed infarct
borders
Well-established granulation
tissue with new blood vessels and
collagen deposition
2–8
wk
Gray-white scar,
progressive from
border toward
core of infarct
Increased collagen deposition,
with decreased cellularity
>2
mo
Scarring complete Dense collagenous scar
Sarcolemmal
disruption;
mitochondrial
amorphous
densities
Chronic forms of ischemic heart disease:
1. microfocal diffuse cardiosclerosis, caused by repeated attacks of a stenocardia.
2. macrofocal myocardial infarction, developed as a result suffering and organized
myocardial necrosis.
3. Chronic cardiac aneurysm - focal bulging of the heart wall in the background
cardiosclerosis.
Cerebrovascular disease
Cerebrovascular disease - characterized by ischemic attack against the
background of atherosclerosis and hypertension.
The most common cerebrovascular disorders are global ischemia, embolism,
hypertensive intraparenchymal hemorrhage, and ruptured aneurysm.
There are three groups.
1. Diseases with ischemic brain injury:
a) ischemic encephalopathy
b) ischemic cerebral infarction
c) hemorrhagic cerebral infarction.
2. Intracranial hemorrhage:
a) intracerebral hemorrhage
b) subarachnoid hemorrhage
c) mixed hemorrhage
3. hypertensive cerebrovascular disease:
a) lacunar infarcts, characterized by the formation of small cysts in the subcortical
nuclei
b) slit hemorrhages characterized by demyelination of neurons and gliosis
arteriologialinosis
c) hypertensive encephalopathy characterized by fibrinoid necrosis of the vessel
walls, petechial hemorrhages and swelling.
The practical part of the subject:
Micropreparations: In the study micropreparations pay attention to educational
elements lettered in parentheses.
1.
Atherosclerotic plaque in the aorta. H & E stain. The aortic intima visible
sediments fat-protein mass and proliferation of connective tissue (a). In the center
of the plaque observed foam cells, cholesterol crystals, necrotic detritus (b). The
surface of the fibrous plaque has hyalinized tire (c) lined with endothelium, (d) In
the interior of the plaque can be seen smooth muscle cells, macrophages,
lymphocytes, (e), section atheromatosis with parietal thrombus (f). On the
periphery of the newly formed vessels are marked (g).
2.
The myocardium in hypertensive disease. H & E stain. In the myocardial
hypertrophic cardiomyocytes increased with hyperchromatic nuclei (a) in the
interstitial tissue is observed proliferation of connective tissue (b), the walls of the
arterioles hyalinized (c).
3.
Arteriolosklerotic kidney. H & E stain. The walls of the arterioles of
kidney significantly thickened due to accumulation of hyaline (a), the lumen of
narrowed in some places obliterated (b). Most of the glomeruli sleeping, replaced
by connective tissue or hyaline masses (c), the tubular epithelium atrophy,
flattened (d). Surviving nephrons compensatory hypertrophied (t). Number of
interstitial connective tissue is increased (f)
4.
Myocardial infarction. H & E stain. In Myocardium observed necrosis area
of muscle fibers (a), non-nuclear cardiomyocytes (b). On the periphery of the
necrotic zone demarcation inflammation observed: advanced full-blooded, thinwalled vessels with a marginal standing leukocytes (c), perivascular hemorrhage
(d), expressed infiltration of polymorphonuclear leukocytes (e).
5.
Postinfarction macrofocal cardiosclerosis. H & E stain. The myocardium
is observed large cicatricial field (a) represented by mature fibrous connective
tissue with single fibrocytes, on the periphery of the focus of increasing muscle
fiber with large hyperchromatic nuclei (b).
Macropreparations.
1. Atherosclerosis of the aorta.
In preparation of the abdominal aorta, sharply distorted by the presence of multiple
saccular protrusions in the wall (aneurysm) in the cavity which are thrombotic
overlay (dilatation thrombi). Uneven Intima with a lot of dense yellowish-whitish
structures (plaques), protruding into the lumen. Some ulceration and deposition of
calcium salts in the form of a gray-white solid mass.
The reasons: violation of combinations of fat and protein metabolism to damage
the endothelium of the arteries.
Complications: thromboembolism in a large circle of blood circulation, with
possible myocardial infarction and brain, kidneys and spleen, intestine and
gangrene of the lower limbs; rupture of an aortic aneurysm.
Outcome: determined by the development of complications.
2. cardiac hypertrophy in hypertensive disease.
The heart increased in size considerably thickened wall of the left ventricle to 3.5
cm, increased trabecular volume and papillary muscle of the left ventricle. Heart
weight of 800 grams. The cavity of the left ventricle expanded. In the context of
the myocardium dim, clay species.
Causes: Chronic hemodynamic load on the heart.
Complications: tonogennaya dilation and concentric hypertrophy (step
compensation) is replaced with the development of myogenic dilatation eccentric
hypertrophy (decompensated).
The outcome: chronic heart failure.
3. Primary-contracted kidney.
The kidney is significantly reduced in size, pale, thick consistency, fine grain
surface. In the context of a typical pattern renal erased border cortical and
medullary layer is not defined in the parenchyma proliferation of connective tissue
gray-white color.
Reasons: chronic circulatory failure resulting hyalinosis arterioles and circulatory
sclerosis branches of the renal artery in hypertensive disease.
Complications: uremia.
The outcome: chronic renal failure.
4. Atherosclerotic nephrosclerosis. Kidney slightly reduced in size, its surface is
large tuberous, due to the plurality of star-shaped scar retraction. The consistency
is firm, drawing on the cut renal relatively preserved, visible wedge portions
subcapsular parenchyma atrophy.
Reasons: chronic circulatory failure as a result of a partial obstruction of the lumen
of the renal artery atherosclerotic plaque (arteriosclerosis segmental).
Complications: symptomatic renovascular hypertension.
The outcome: chronic renal failure.
5. Myocardial infarction. In the side wall of the left ventricle, in the apex and the
anterior part of the interventricular septum of the heart, there is a pathological site
irregular sink on the cut submitted drain pockets of gray-yellow in color
(coagulation necrosis), around the area of hemorrhage and hyperemia (demarcation
zone). In the lumen of the descending branch of the left coronary artery occlusive
thrombus. Sclerotic coronary arteries with fibrous plaques. From the endocardial
thrombotic visible overlay.
Causes: thrombosis, long spasm, thromboembolism, functional overstrain
infarction in the presence of arteriosclerotic occlusion.
Complications in the early period- pulmonary edema, cardiogenic shock,
arrhythmias and conduction, myocardial rupture (3-10 day when transmural
infarction) or acute rupture of the aneurysm (4-14 days), thromboembolism
Complications of late period: chronic cardiac aneurysm, Dressler's syndrome
(pericarditis, pleurisy, fever, blood eosinophilia).
Outcome: congestive heart failure, pulmonary edema, or brain macrofocal
cardiosclerosis, chronic coronary artery disease.
6.
Hemopericardium with cardiac tamponade.
In preparation of the heart with heart shirt in cross section. Pericardial
accumulation of coagulated blood. On the back wall of the left ventricle there is a
section of necrosis in violation of the integrity of the myocardium, measuring
about 2cm.
The reasons: the gap acute or chronic heart aneurysm, rupture of the heart wall
when transmural infarction (under miomalyatsii), rupture of the heart wall in
obesity.
Outcome: unfavorable.
7.
Hematoma of the brain.
The parietal-temporal region of the right hemisphere - the accumulation of
coagulated blood brownish-red color. In the matter of the brain hemorrhage
destroyed "red softening of the brain."
Reason: breaks microaneurysm arterioles and small arteries, or hyalinized vascular
microcirculation, at least in the ulceration of an atherosclerotic plaque.
Complications: paralysis.
The outcome: poor in breaking the blood into the ventricles, rarely a cyst.
8. Ischemic cerebral infarction.
The left hemisphere of the brain, in the subcortical nuclei, seen hotbed of irregular
shape, presented this mass of gray, the size of 1.5 cm × 3 cm, with clear boundaries
- a "hotbed of gray softening." The surrounding brain tissue swelling with
diapedetic hemorrhages.
Causes of thrombosis and atherosclerotic lesions of cerebral arteries precerebral
rarely thromboembolism, long spasm.
Complications are determined localization nekroza- paralysis, paresis.
The outcome: a cyst.
Test control
Select one or more correct answers.
1. When atherosclerosis affects
1) veins
2) capillaries
3) arterioles
4) large and medium arteries
2. successive stages of atherosclerosis
1) aterocalcinosis (4)
2) fibrous plaques (2)
3) complicated lesions (3)
4) fatty Streaks (1)
3. TYPES lipoprotein metabolism disorders in atherosclerosis
1) reduction in LDL - cholesterol
2) increase the level of LDL - cholesterol
3) increase in HDL - cholesterol
4) improving the abnormal lipoprotein
4. IMPROVING LDL in plasma leads to
1) the destruction of elastic fibers
2) increased permeability of the endothelium
3) damage and loss of endothelial cells
4) increasing adhesion of monocytes to Endothelial cells
5. foam cells come from
1) macrophages
2) lymphocytes
3) mast cells
4) plasma cells
5) adventitial cells
6) smooth muscle cells
6. Mönckeberg medial sclerosis strikes lining of arteries
1) Internal
2) Medium
3) outer
7. The risk factors for atherosclerosis
1) stress
2) obesity
3) hyperuricemia
4) male
5) fermentopathy
6) hypercalcemia
8. abdominal aortic aneurysm is typical for
1) Syphilis
2) Rheumatism
3) atherosclerosis
4) arteriosclerosis
9. The form of clinical course of arterial hypertension
1) Secondary
2) idiopathic
3) malignant
4) benign
10. The causes and risk factors of development of secondary hypertension
1) pheochromocytoma
2) coarctation of the aorta
3) violation of the separation of sodium by the kidneys
4) genetic disorders of the renin-angiotensin system
11. Morphological changes of arterioles in hypertension
1) arteriolitis
2) caseous necrosis
3) fibrinoid necrosis
4) nodular periarteritis
5) hyaline arteriolosclerosis
6) hyperplastic arteriolosclerosis
12. arteriolosclerosis hyaline vascular lumen
1) is narrowed
2) expanded
3) is not changed
13. renal size with hypertension
1) Increase
2) conventional
3) Reduce
14. The possibility of changes in the kidney with renal artery atherosclerosis
1) infarcts
2) amyloidosis
3) embolic purulent nephritis
4) hydronephrosis transformation
15. CHANGES large vessels in essential hypertension
1) fat spots and stripes
2) hyalinosis walls
3) productive vasculitis
4) circular arteriosclerosis
5) aneurysm
16. The possibility of changes in the arterioles in essential hypertension
1) proliferation of endothelial
2) hyalinosis
3) giperelastoz
4) hypertrophy of muscle cells
5) fibrinoid necrosis
17. fatal complications in atherosclerosis mesenteric artery
1) intestinal obstruction
2) bowel gangrene
3) fibrinous colitis
4) ischemic colitis
18. SIGNS eccentric myocardial hypertrophy in hypertension
1) an increase in heart size in diameter
2) the expansion of adipose tissue
3) expansion of cavities
4) myocardial atrophy
19. Ischemic heart disease pathogenetic CONNECTION
1) with rheumatoid koronariitom
2) with mitral valve stenosis
3) with coronary atherosclerosis
4) with essential hypertension
20. forms of acute ischemic heart disease
1) cardiomyopathy
2) acute focal ischemic myocardium dystrophy
3) myocardial infarction
4) chronic cardiac aneurysm
5) sudden cardiac death
21. The most frequent localization of myocardial infarction
1) the right atrium
2) the left atrium
3) the right ventricle
4) the left ventricle
22. stage during myocardial infarction
1) necrotic
2) Mixed
3) ischemic
4) Organization
5) Compensatory
23. BASE cerebrovascular disease is
1) syphilis, cerebrovascular
2) atherosclerosis of cerebral arteries
3) essential hypertension
4) Hydrocephalus
5) rheumatoid vasculitis
24. ischemic cerebral infarction develops in
1) vessels in the brain rupture of microaneurysms
2) thrombosis of cerebral arteries
3) thrombosis of the carotid and vertebral arteries
25. Morphological manifestations of cerebrovascular Diseases
1) congenital aneurysm of the brain arteries
2) ischemic cerebral infarction
3) bleeding in the brain
4) Encephalitis
26. Types of Angina pectoris
1) labile
2) stable
3) disappear
4) spastic
5) Prinzmetala
6) unstable
27. macroscopic myocardial infarction revealed through
1) 1-2h
2) 4-6 h
3) 18-24h
4) 72 hours
28. microscopic features of myocardial infarction
1) plasma-coagulation
2) fatty degeneration
3) mucoid swelling
4) vacuolization of the cytoplasm
5) karyopyknosis, karyorrhexis
29. TYPES myocardial infarction localization
1) subendocardial
2) chordal
3) transmural
4) intramural
5) the valve
6) subepicardial
30. CHANGES cardiomyocytes of Angina pectoris
1) atrophy
2) kariolizis
3) fatty degeneration
4) the disappearance of glycogen
ORENBURG STATE MEDICAL UNIVERSITY
DEPARTMENT OF PATHOLOGICAL ANATOMY
METHODICAL MANUAL FOR PRACTICAL TRAINING FOR STUDENTS OF
FOREIGN FACULTY
THEME:
DISEASES OF LIVER AND BILIARY SYSTEM.
HEPATITIS. CIRRHOSIS. LIVER CANCER. CHOLELITHIASIS.
DISEASES OF LIVER AND BILIARY SYSTEM.
HEPATITIS. CIRRHOSIS. LIVER CANCER. CHOLELITHIASIS.
VIRAL HEPATITIS
Systemic viral infections can involve the liver as in (1) infectious mononucleosis
(Epstein-Barr virus), which may cause a mild hepatitis during the acute phase; (2)
cytomegalovirus infection, particularly in the newborn or immunosuppressed
patient; and (3) yellow fever (yellow fever virus), which has been a major and
serious cause of hepatitis in tropical countries. Infrequently, in children and
immunosuppressed patients, the liver is affected in the course of rubella,
adenovirus, herpesvirus, or enterovirus infections. However, unless otherwise
specified, the term viral hepatitis is applied for hepatic infections caused by a
group of viruses known as hepatotropic virus (hepatitis viruses A, B, C, D, and E)
that have a particular affinity for the liver ( Table 1). We first present the main
features of each hepatotropic virus, followed by a discussion of the
clinicopathologic characteristics of acute and chronic viral hepatitis.
TABLE 1 - The Hepatitis Viruses
Virus
Type
virus
Hepatitis A
of ssRNA
Hepatitis B
partially
dsDNA
Hepatitis
C
Hepatitis D
Hepatitis
E
ssRNA
ssRNA
Circular
defective
ssRNA
Viral family Hepatovirus; Hepadnavirus Flaviridae Subviral
Calicivirus
related
to
particle
in
picornavirus
Deltaviridae
family
Route
of Fecal-oral
Parenteral,
transmission (contaminated sexual
food or water) contract,
perinatal
Parenteral; Parenteral
intranasal
cocaine
use is a
risk factor
Mean
incubation
period
1–4 months
7–8 weeks Same as HBV 4–5 weeks
10%
∼80%
2–4 weeks
Frequency Never
of chronic
liver disease
Fecal-oral
5%
Never
(coinfection);
≤70%
for
superinfection
Hepatitis B
Hepatitis
C
Hepatitis D
Virus
Hepatitis A
Diagnosis
Detection of Detection of PCR for
serum
IgM HBsAg
or HCV
antibodies
antibody to RNA; 3rdHBcAg
generation
ELISA for
antibody
detection
Detection of
IgM and IgG
antibodies;
HDV RNA
serum; HDAg
in liver
Hepatitis
E
PCR for
HEV
RNA;
detection
of serum
IgM and
IgG
antibodies
Hepatitis A Virus
Hepatitis A virus (HAV), the scourge of military campaigns since antiquity, is a
benign, self-limited disease with an incubation period of 3 to 6 weeks. HAV does
not cause chronic hepatitis or a carrier state and only rarely causes fulminant
hepatitis, so the fatality rate associated with HAV is about 0.1%. HAV occurs
throughout the world and is endemic in countries with substandard hygiene and
sanitation, where populations may have detectable antibodies to HAV by the age of
10 years. Clinical disease tends to be mild or asymptomatic, and is rare after
childhood. In this population acute HAV tends to be a sporadic febrile illness.
Affected individuals have nonspecific symptoms such as fatigue and loss of
appetite, and often develop jaundice.
Hepatitis B Virus (HBV)
HBV can produce (1) acute hepatitis with recovery and clearance of the virus, (2)
nonprogressive chronic hepatitis, (3) progressive chronic disease ending in
cirrhosis, (4) fulminant hepatitis with massive liver necrosis, and (5) an
asymptomatic carrier state. HBV-induced chronic liver disease is an important
precursor for the development of hepatocellular carcinoma. The HBV genome
contains four open reading frames coding for:
• A nucleocapsid “core” protein (HBcAg, hepatitis B core antigen) and a
longer polypeptide transcript with a precore and core region, designated
HBeAg (hepatitis B “e” antigen). The precore region directs the HBeAg
polypeptide toward secretion into blood, whereas HBcAg remains in
hepatocytes for the assembly of complete virions.
•
Envelope glycoproteins (HBsAg, hepatitis B surface antigen), which consist
of three related proteins: large HBsAg (containing Pre-S1, Pre-S2, and S),
middle HBsAg (containing Pre-S2 and S), and small HBsAg (containing S
only). Infected hepatocytes are capable of synthesizing and secreting
massive quantities of noninfective surface protein (mainly small HBsAg).
•
A polymerase (Pol) that exhibits both DNA polymerase activity and reverse
transcriptase activity. Genomic replication occurs via an intermediate RNA
template, through a unique replication cycle: DNA ➙ RNA ➙ DNA.
•
HBx protein, which is necessary for virus replication and may act as a
transcriptional transactivator of the viral genes and a wide variety of host
genes. It has been implicated in the pathogenesis of liver cancer in HBV
infection.
Hepatitis C Virus
Hepatitis C virus (HCV) is a major cause of liver disease worldwide, with
approximately 170 million people affected. Approximately 4.1 million Americans,
or 1.6% of the population, have chronic HCV infection. This makes HCV the most
common chronic blood-borne infection and accounts for almost half of all US
individuals with chronic liver disease. Notably, there has been a decrease in the
annual incidence of infection from its mid-1980s peak of over 230,000 new
infections per year to a current 19,000 new infections per year. This welcome
decline resulted primarily from a marked reduction in transfusion-associated
causes as a result of screening procedures. Nevertheless, the number of patients
with chronic infection will continue to increase, as a result of potential lifelong
persistence of HCV infection. In contrast to HBV, progression to chronic disease
occurs in the majority of HCV-infected individuals, and cirrhosis eventually occurs
in 20% to 30% of individuals with chronic HCV infection. Thus, HCV is the most
common cause of chronic liver disease in the United States and the most common
indication for liver transplantation.
Hepatitis D Virus
Also called “hepatitis D virus,” hepatitis D virus (HDV) is a unique RNA virus that
is dependent for its life cycle on HBV. Infection with HDV arises in the following
settings.
• Acute coinfection occurs following exposure to serum containing both HDV
and HBV. The HBV must become established first to provide the HBsAg
necessary for development of complete HDV virions.
•
Superinfection occurs when a chronic carrier of HBV is exposed to a new
inoculum of HDV. This results in disease 30–50 days later.
•
Helper-independent latent infection observed in the liver transplant setting.
Morphology of Acute and Chronic Hepatitis.
The morphologic changes in acute and chronic viral hepatitis are shared among the
hepatotropic viruses and can be mimicked by drug reactions or autoimmune liver
disease. Tissue alterations caused by acute infection with HAV, HBV, HCV, and
HEV are generally similar, as is the chronic hepatitis caused by HBV, HCV, and
HBV + HDV. A few histologic changes may be indicative of a particular type of
virus. HBV-infected hepatocytes may show a cytoplasm packed with spheres and
tubules of HBsAg, producing a finely granular cytoplasm (“ground-glass
hepatocytes ). HCV-infected livers frequently show lymphoid aggregates within
portal tracts and focal lobular regions of hepatocyte macrovesicular steatosis,
which are to be distinguished from the extensive panlobular microvesicular and
macrovesicular steatosis seen in many forms of toxic hepatitis (e.g., alcoholinduced).
Acute Hepatitis. With acute hepatitis hepatocyte injury takes the form of diffuse
swelling (“ballooning degeneration”), so the cytoplasm looks empty and contains
only scattered eosinophilic remnants of cytoplasmic organelles. An inconstant
finding is cholestasis, with bile plugs in canaliculi and brown pigmentation of
hepatocytes. The canalicular bile plugs result from cessation of the contractile
activity of the hepatocyte pericanalicular actin microfilament web. Several patterns
of hepatocyte cell death are seen.
•
Rupture of the cell membrane leads to cell death and focal loss of
hepatocytes. The sinusoidal collagen reticulin framework collapses where
the cells have disappeared, and scavenger macrophage aggregates mark
sites of hepatocyte loss.
•
Apoptosis, caused by anti-viral cytotoxic (effector) T cells. Apoptotic
hepatocytes shrink, become intensely eosinophilic, and have fragmented
nuclei; effector T cells may still be present in the immediate vicinity.
Apoptotic cells are rapidly phagocytosed by macrophages and hence might
be difficult to find, despite a brisk rate of hepatocyte injury.
•
In severe cases of acute hepatitis, confluent necrosis of hepatocytes may lead
to bridging necrosis connecting portal-to-portal, central-to-central, or
portal-to-central regions of adjacent lobules. Hepatocyte swelling and
regeneration compress sinusoids, and the more or less radial array of
hepatocyte plates around terminal hepatic veins is lost.
Inflammation is a characteristic and usually prominent feature of acute hepatitis.
Kupffer cells undergo hypertrophy and hyperplasia and are often laden with
lipofuscin pigment as a result of phagocytosis of hepatocellular debris. The portal
tracts are usually infiltrated with a mixture of inflammatory cells. The
inflammatory infiltrate may spill over into the adjacent parenchyma, causing
apoptosis of periportal hepatocytes. This is known as interface hepatitis, which
can occur in acute and chronic hepatitis. Cells in the canals of Hering proliferate,
forming ductular structures at the parenchymal interface (ductular reaction).
Chronic Hepatitis. The histologic features of chronic hepatitis range from
exceedingly mild to severe. In the mildest forms, inflammation is limited to portal
tracts and consists of lymphocytes, macrophages, occasional plasma cells, and rare
neutrophils or eosinophils. Liver architecture is usually well preserved, but
smoldering hepatocyte apoptosis throughout the lobule may occur in all forms of
chronic hepatitis. In chronic HCV infection, common findings (occurring in 55%
of HCV infections) are lymphoid aggregates and bile duct reactive changes in
the portal tracts, and focal mild to moderate macrovesicular steatosis. The steatosis
is more prevalent and prominent in HCV genotype 3 infections. In all forms of
chronic hepatitis, continued interface hepatitis and bridging necrosis between
portal tracts and portal tracts-to-terminal hepatic veins, are harbingers of
progressive liver damage.
The hallmark of chronic liver damage is the deposition of fibrous tissue. At
first, only portal tracts show increased fibrosis, but with time periportal septal
fibrosis occurs, followed by linking of fibrous septa (bridging fibrosis), especially
between portal tracts. In clinical practice, several systems have been used to score
the severity and progression of liver damage due to HBV and HCV infection. In
each system the key elements are inflammation and hepatocyte destruction (grade),
and the severity of fibrosis (stage)
Continued loss of hepatocytes and fibrosis results in cirrhosis. It is
characterized by irregularly sized nodules separated by variable but mostly broad
scars, and is often referred to as post-necrotic cirrhosis . However, this term is not
specific to viral etiology, and is applied to all forms of cirrhosis in which the liver
shows large, irregular-sized nodules with broad scars. In addition to viral hepatitis,
autoimmune hepatitis, hepatotoxins (carbon tetrachloride, mushroom poisoning),
pharmaceutical drugs (acetaminophen, α-methyldopa), and even alcohol (discussed
later) can give rise to cirrhotic livers with irregular-sized large nodules. In about
20% of cases the inciting cause of the cirrhosis cannot be determined, and these are
labeled as cryptogenic cirrhosis. Thus, the morphology of the end-stage cirrhotic
liver is often not helpful in determining the basis of the liver injury.
ALCOHOLIC LIVER DISEASE
Excessive alcohol (ethanol) consumption is the leading cause of liver disease in
most Western countries. In the United States, 50% of the population 18 years of
age or older drink alcohol. A subset of these individuals suffer serious health
consequences associated with alcoholism ( Chapter 9 ). Of greatest impact is
alcoholic liver disease, which affects more than 2 million Americans and causes
27,000 deaths a year. There are three distinctive, albeit overlapping, forms of
alcoholic liver disease: (1) hepatic steatosis (fatty liver disease), (2) alcoholic
hepatitis, and (3) cirrhosis ( Fig. 18-22 ). The morphology of the three forms of
alcoholic liver disease is presented first, followed by a discussion of their
pathogenesis.
Morphology.
Hepatic Steatosis (Fatty Liver). After even moderate intake of alcohol,
microvesicular lipid droplets accumulate in hepatocytes. With chronic intake of
alcohol, lipid accumulates creating large, clear macrovesicular globules that
compress and displace the hepatocyte nucleus to the periphery of the cell.
Macroscopically, the fatty liver of chronic alcoholism is a large (as heavy as 4 to 6
kg), soft organ that is yellow and greasy. Although there is little or no fibrosis at
the outset, with continued alcohol intake fibrous tissue develops around the
terminal hepatic veins and extends into the adjacent sinusoids. The fatty change is
completely reversible if there is abstention from further intake of alcohol.
Alcoholic Hepatitis
characterized by:
(Alcoholic
Steatohepatitis).
Alcoholic
hepatitis
is
1.
Hepatocyte swelling and necrosis: Single or scattered foci of cells
undergo swelling (ballooning) and necrosis. The swelling results from the
accumulation of fat and water, as well as proteins that normally are
exported. In some cases there is cholestasis in surviving hepatocytes and
mild deposition of hemosiderin (iron) in hepatocytes and Kupffer cells.
2.
Mallory bodies: Scattered hepatocytes accumulate tangled skeins of
cytokeratin intermediate filaments such as cytokeratin 8 and 18, in complex
with other proteins such as ubiquitin. Mallory bodies are visible as
eosinophilic cytoplasmic clumps in hepatocytes ( Fig. 18-23 ). These
inclusions are a characteristic but not specific feature of alcoholic liver
disease, since they also present in NAFLD, PBC, Wilson disease, chronic
cholestatic syndromes, and hepatocellular tumors.
3.
Neutrophilic reaction: Neutrophils permeate the hepatic lobule and
accumulate around degenerating hepatocytes, particularly those having
Mallory bodies. Lymphocytes and macrophages also enter portal tracts and
spill into the parenchyma.
4.
Fibrosis: Alcoholic hepatitis is almost always accompanied by prominent
activation of sinusoidal stellate cells and portal tract fibroblasts, giving rise
to fibrosis. Most frequently fibrosis is sinusoidal and perivenular,
separating parenchymal cells; occasionally, periportal fibrosis may
predominate, particularly with repeated bouts of heavy alcohol intake.
NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)
NAFLD is a group of conditions that have in common the presence of hepatic
steatosis (fatty liver), in individuals who do not consume alcohol, or do so in very
small quantities (less than 20 g of ethanol/week). It has become the most common
cause of chronic liver disease in the United States, and in its various forms,
probably affects more than 30% of the population. However, these estimates are
approximate, because fatty liver without other complications may not be detected
clinically. NAFLD includes simple hepatic steatosis, steatosis accompanied by
minor, non-specific inflammation, and non-alcoholic steatohepatitis (NASH).
Steatosis with or without non-specific inflammation is generally a stable condition
without significant clinical problems. In contrast, NASH is a condition in which
there is hepatocyte injury that may progress to cirrhosis in 10% to 20% of cases.
The main components of NASH are hepatocyte ballooning, lobular inflammation,
and steatosis. With progressive disease fibrosis occurs. NASH affects men and
women equally and the condition is strongly associated with obesity and the other
components of the metabolic syndrome, such as dyslipidemia, hyperinsulinemia
and insulin resistance. It is estimated that more than 70% of obese individuals have
some form of NAFLD. It is the most common cause of so-called cryptogenic
cirrhosis, namely cirrhosis of “unknown” origin. NAFLD contributes to the
progression of other liver diseases such as HCV infection and HCC. The epidemic
of obesity in the United States heightens concern that NAFLD will increase in
prevalence.
The precise mechanisms of steatosis and hepatocellular damage in NAFLD are not
entirely known, but genetics and environment play a role in the pathogenesis. A
“two-hit” model of pathogenesis has been proposed, encompassing two sequential
events: (1) hepatic fat accumulation and, (2) hepatic oxidative stress. The oxidative
stress acts upon the accumulated hepatic lipids, resulting in lipid peroxidation and
the release of lipid peroxides, which can produce reactive oxygen species.
Morphology. Steatosis usually involves more than 5% of the hepatocytes and
sometimes more than 90%. Large (macrovesicular) and small (microvesicular)
droplets of fat, predominantly triglycerides, accumulate within hepatocytes ( Fig.
18-25A ). At the most clinically benign end of the spectrum, there is no
appreciable hepatic inflammation, hepatocyte death, or scarring, despite persistent
elevation of serum liver enzymes. Steatohepatitis (NASH) is characterized by
steatosis and multifocal parenchymal inflammation, mainly neutrophils, Mallory
bodies, hepatocyte death (both ballooning degeneration and apoptosis), and
sinusoidal fibrosis. Fibrosis also occurs within portal tracts and around terminal
hepatic venules ( Fig. 18-25B ). These histological changes are similar to those of
alcoholic steatohepatitis. Cirrhosis may develop, presumably the result of years of
subclinical progression of the necroinflammatory and fibrotic processes. When
cirrhosis is established, the steatosis or steatohepatitis tends to be reduced and
sometimes is not identifiable.
CIRRHOSIS
The chief worldwide causes of cirrhosis are alcohol abuse, viral hepatitis, and nonalcoholic steatohepatitis (NASH). Other etiologies include biliary disease and iron
overload. Cirrhosis, as the end stage of chronic liver disease, is defined by three
main morphologic characteristics:
•
Bridging fibrous septa in the form of delicate bands or broad scars linking
portal tracts with one another and portal tracts with terminal hepatic veins.
Fibrosis is the key feature of progressive damage to the liver. Fibrosis is a
dynamic process of collagen deposition and remodeling.
•
Parenchymal nodules containing hepatocytes encircled by fibrosis, with
diameters varying from very small (<0.3 cm, micronodules) to large (several
centimeters, macronodules). Nodularity results from cycles of hepatocyte
regeneration and scarring.
•
Disruption of the architecture of the entire liver. The parenchymal injury
and consequent fibrosis are diffuse, extending throughout the liver. Focal
injury with scarring does not constitute cirrhosis, nor does diffuse nodular
transformation without fibrosis.
The central pathogenic processes in cirrhosis are death of hepatocytes,
extracellular matrix (ECM) deposition, and vascular reorganization.
At first the cirrhotic liver is yellowtan, fatty, and enlarged, usually weighing over 2
kg. Over the span of years, it is transformed into a brown, shrunken, nonfatty
organ, sometimes less than 1 kg in weight. Initially the developing fibrous septa
are delicate and extend through sinusoids from central to portal regions as well as
from portal tract to portal tract. Regenerative activity of entrapped parenchymal
hepatocytes generates uniform micronodules. With time the nodularity becomes
more prominent; scattered larger nodules create a “hobnail” appearance on the
surface of the liver. As fibrous septa dissect and surround nodules, the liver
becomes more fibrotic, loses fat, and shrinks progressively in size. Parenchymal
islands are engulfed by wider bands of fibrous tissue, and the liver is converted
into a mixed micronodular and macronodular pattern. Ischemic necrosis and
fibrous obliteration of nodules eventually create broad expanses of tough, pale scar
tissue (“Laennec cirrhosis”). Bile stasis often develops; Mallory bodies are only
rarely evident at this stage. Thus, end-stage alcoholic cirrhosis comes to
resemble, both macroscopically and microscopically, the cirrhosis developing
from viral hepatitis and other causes.
BENIGN NEOPLASMS
Hepatic Adenoma. Benign neoplasms developing from hepatocytes are called
hepatic adenomas or liver cell adenomas. Although they may occur in men,
hepatic adenomas most frequently occur in young women who have used oral
contraceptives; tumors generally regress if contraceptive use is terminated. The
incidence of adenoma is approximately 1 in 100,000. Morphology. Liver cell
adenomas are pale, yellowtan, and frequently bile-stained nodules, found anywhere
in the hepatic substance but often beneath the capsule. They may reach 30 cm in
diameter. Although they are usually well demarcated, encapsulation might not be
present. The tumor commonly presents as a solitary lesion, but multiple lesions
(adenomatosis) can occur. Histologically, liver cell adenomas are composed of
sheets and cords of cells that may resemble normal hepatocytes or have some
variation in cell and nuclear size. Abundant glycogen may generate large
hepatocytes with a clear cytoplasm. Steatosis is commonly present. Portal tracts are
absent; instead, prominent solitary arterial vessels and draining veins are
distributed through the substance of the tumor.
MALIGNANT TUMORS
Malignant tumors occurring in the liver can be primary or metastatic. Most of the
discussion in this section deals with primary hepatic tumors. Most primary liver
cancers arise from hepatocytes and are termed hepatocellular carcinoma (HCC).
Much less common are carcinomas of bile duct origin, cholangiocarcinomas.
Hepatoblastoma is the most common liver tumor of young childhood. Its
incidence, which is increasing, is approximately 1 to 2 in 1 million births. The
tumor is usually fatal within a few years if not treated. This tumor has two
anatomic variants:
•
•
The epithelial type, composed of small polygonal fetal cells or smaller
embryonal cells forming acini, tubules, or papillary structures vaguely
recapitulating liver development
The mixed epithelial and mesenchymal type, which contains foci of
mesenchymal differentiation that may consist of primitive mesenchyme,
osteoid, cartilage, or striated muscle
Hepatocellular Carcinoma (HCC).
On a global basis, there are more than 626,000 new cases per year of primary liver
cancer, almost all being HCC, and approximately 598,000 patients die from this
cancer every year, the third most frequent cause of cancer deaths. About 82% of
HCC cases occur in developing countries with high rates of chronic HBV
infection, such as in southeast Asian and African countries; 52% of all HCC cases
occur in China. In the United States the incidence of liver cancer increased by 25%
between 1993 and 1998, mainly due to HCV and HBV chronic infection.
Morphology. HCC may appear grossly as (1) a unifocal (usually large) mass; (2)
multifocal, widely distributed nodules of variable size; or (3) a diffusely infiltrative
cancer, permeating widely and sometimes involving the entire liver. All three
patterns may cause liver enlargement, particularly the large unifocal and
multinodular patterns. The diffusely infiltrative tumor may blend imperceptibly
into a cirrhotic liver background.
HCCs are usually paler than the surrounding liver, and sometimes take on a green
hue when composed of well-differentiated hepatocytes capable of secreting bile.
All patterns of HCCs have a strong propensity for invasion of vascular
structures. Extensive intrahepatic metastases ensue, and occasionally, long,
snakelike masses of tumor invade the portal vein (with occlusion of the portal
circulation) or inferior vena cava, extending even into the right side of the heart.
HCC spreads extensively within the liver by obvious contiguous growth and by the
development of satellite nodules, which can be shown by molecular methods to be
derived from the parent tumor. Metastasis outside the liver is primarily via vascular
invasion, especially into the hepatic vein system, but hematogenous metastases,
especially to the lung, tend to occur late in the disease. Lymph node metastases to
the perihilar, peripancreatic, and para-aortic nodes above and below the diaphragm
are found in fewer than half of HCCs that spread beyond the liver. If HCC with
venous invasion is identified in explanted livers at the time of liver transplantation,
tumor recurrence is likely to occur in the transplanted donor liver.
HCCs range from well-differentiated to highly anaplastic undifferentiated lesions.
In well-differentiated and moderately differentiated tumors, cells that are
recognizable as hepatocytic in origin are disposed either in a trabecular pattern
(recapitulating liver cell plates) or in an acinar, pseudoglandular pattern. In poorly
differentiated forms, tumor cells can take on a pleomorphic appearance with
numerous anaplastic giant cells, can be small and completely undifferentiated, or
may even resemble a spindle cell sarcoma.
Cholangiocarcinoma (CCA).
Cholangiocarcinoma, the second most common hepatic malignant tumor after
HCC, is a malignancy of the biliary tree, arising from bile ducts within and outside
of the liver. Morphology. Extrahepatic CCAs are generally small lesions at the
time of diagnosis. Most tumors appear as firm, gray nodules within the bile duct
wall; some may be diffusely infiltrative lesions; others are papillary, polypoid
lesions. Most are adenocarcinomas that may or may not secrete mucin.
Uncommonly, squamous features are present. For the most part, an abundant
fibrous stroma accompanies the epithelial proliferation. Klatskin tumors generally
have slower growth than other CCAs, show prominent fibrosis, and infrequently
involve distal metastases.
Intrahepatic CCAs occur in the noncirrhotic liver and may track along the
intrahepatic portal tract system to create a treelike tumorous mass within a portion
of the liver. Alternatively, a massive tumor nodule may develop. In either instance,
vascular invasion and propagation along portal lymphatics may be prominent
features, giving rise to extensive intrahepatic metastasis. By microscopy, CCAs
resemble adenocarcinomas arising in other parts of the body, and they may show
the full range of morphologic variation. Most are well- to moderately differentiated
sclerosing adenocarcinomas with clearly defined glandular and tubular structures
lined by cuboidal to low columnar epithelial cells. These neoplasms are usually
markedly desmoplastic, with dense collagenous stroma separating the glandular
elements. As a result, the tumor substance is extremely firm and gritty. Lymph
node metastasis and hematogenous metastases to the lungs, bones (mainly
vertebrae), adrenals, brain, or elsewhere are present at autopsy in about 50% of
cases.
CHOLECYSTITIS
Inflammation of the gallbladder may be acute, chronic, or acute superimposed on
chronic. It almost always occurs in association with gallstones. In the United States
cholecystitis is one of the most common indications for abdominal surgery. Its
epidemiologic distribution closely parallels that of gallstones.
Acute calculous cholecystitis is an acute inflammation of the gallbladder,
precipitated 90% of the time by obstruction of the neck or cystic duct. It is the
primary complication of gallstones and the most common reason for emergency
cholecystectomy. Cholecystitis without gallstones called acalculous cholecystitis
may occur in severely ill patients and accounts for about 10% of patients with
cholecystitis. Morphology. In acute cholecystitis the gallbladder is usually
enlarged and tense, and it may assume a bright red or blotchy, violaceous to greenblack discoloration, imparted by subserosal hemorrhages. The serosal covering is
frequently layered by fibrin and, in severe cases, by a definite suppurative,
coagulated exudate. There are no specific morphologic differences between acute
acalculous and calculous cholecystitis, except for the absence of macroscopic
stones in the acalculous form. In calculous cholecystitis, an obstructing stone is
usually present in the neck of the gallbladder or the cystic duct. The gallbladder
lumen may contain one or more stones and is filled with a cloudy or turbid bile that
may contain large amounts of fibrin, pus, and hemorrhage. When the contained
exudate is virtually pure pus, the condition is referred to as empyema of the
gallbladder. In mild cases the gallbladder wall is thickened, edematous, and
hyperemic. In more severe cases it is transformed into a green-black necrotic
organ, termed gangrenous cholecystitis, with small-to-large perforations. The
invasion of gas-forming organisms, notably clostridia and coliforms, may cause an
acute “emphysematous” cholecystitis. The inflammatory reactions are not
histologically distinctive and consist of the usual patterns of acute inflammation.
Chronic cholecystitis may be a sequel to repeated bouts of mild to severe acute
cholecystitis, but in many instances it develops in the apparent absence of
antecedent attacks. Since it is associated with cholelithiasis in more than 90% of
cases, the patient populations are the same as those for gallstones. The evolution of
chronic cholecystitis is obscure, in that it is not clear that gallstones play a direct
role in the initiation of inflammation or the development of pain, particularly since
chronic acalculous cholecystitis shows symptoms and histology similar to those of
the calculous form. Rather, supersaturation of bile predisposes to both chronic
inflammation and, in most instances, stone formation. Microorganisms, usually E.
coli and enterococci, can be cultured from the bile in about one third of cases.
Unlike acute calculous cholecystitis, obstruction of gallbladder outflow is not a
requisite. Nevertheless, the symptoms of calculous chronic cholecystitis are similar
to those of the acute form and range from biliary colic to indolent right upper
quadrant pain and epigastric distress. Since most gallbladders that are removed at
elective surgery for gallstones show features of chronic cholecystitis, one must
conclude that biliary symptoms often emerge following long-term coexistence of
gallstones and low-grade inflammation.
Morphology. The morphologic changes in chronic cholecystitis are extremely
variable and sometimes minimal. The serosa is usually smooth and glistening but
may be dulled by subserosal fibrosis. Dense fibrous adhesions may remain as
sequelae of preexistent acute inflammation. On sectioning, the wall is variably
thickened, and has an opaque gray-white appearance. In the uncomplicated case
the lumen contains fairly clear, green-yellow, mucoid bile and usually stones. The
mucosa itself is generally preserved.
On histologic examination the degree of inflammation is variable. In the mildest
cases, only scattered lymphocytes, plasma cells, and macrophages are found in the
mucosa and in the subserosal fibrous tissue. In more advanced cases there is
marked subepithelial and subserosal fibrosis, accompanied by mononuclear cell
infiltration. Reactive proliferation of the mucosa and fusion of the mucosal folds
may give rise to buried crypts of epithelium within the gallbladder wall.
Outpouchings of the mucosal epithelium through the wall (Rokitansky-Aschoff
sinuses) may be quite prominent. Superimposition of acute inflammatory changes
implies acute exacerbation of an already chronically injured gallbladder.
In rare instances extensive dystrophic calcification within the gallbladder wall may
yield a porcelain gallbladder, notable for a markedly increased incidence of
associated cancer. Xanthogranulomatous cholecystitis is also a rare condition in
which the gallbladder has a massively thickened wall, is shrunken, nodular, and
chronically inflamed with foci of necrosis and hemorrhage. Finally, an atrophic,
chronically obstructed gallbladder may contain only clear secretions, a condition
known as hydrops of the gallbladder.
CARCINOMA OF THE GALLBLADDER
Carcinoma of the gallbladder is the most common malignancy of the extrahepatic
biliary tract. It is slightly more common in women and occurs most frequently in
the seventh decade of life. The incidence in the United States is 1 in 50,000. Only
rarely is it discovered at a resectable stage, and the mean 5-year survival rate has
remained for many years at about 5% to 12% despite surgical intervention. The
most important risk factor associated with gallbladder carcinoma is gallstones
(cholelithiasis), which are present in 95% of cases. However, it should be noted
that only 0.5% of patients with gallstones develop gallbladder cancer after twenty
or more years. In Asia, where pyogenic and parasitic diseases of the biliary tree are
common, the coexistence of gallstones in gallbladder cancer is much lower.
Presumably, gallbladders containing stones or infectious agents develop cancer as
a result of irritative trauma and chronic inflammation. Carcinogenic derivatives of
bile acids are believed to play a role. Morphology. Carcinomas of the gallbladder
show two patterns of growth: infiltrating and exophytic. The infiltrating pattern is
more common and usually appears as a poorly defined area of diffuse thickening
and induration of the gallbladder wall that may cover several square centimeters or
may involve the entire gallbladder. Deep ulceration can cause direct penetration of
the gallbladder wall or fistula formation to adjacent viscera into which the
neoplasm has grown. These tumors are scirrhous and have a very firm consistency.
The exophytic pattern grows into the lumen as an irregular, cauliflower mass but at
the same time invades the underlying wall. The luminal portion may be necrotic,
hemorrhagic, and ulcerated. The most common sites of involvement are the fundus
and the neck; about 20% involve the lateral walls.
Most carcinomas of the gallbladder are adenocarcinomas. They may be derived
from adenomas, which are present in 1% of cholecystectomy specimens. Some of
the carcinomas are papillary in architecture and are well to moderately
differentiated; others are infiltrative and poorly differentiated to undifferentiated .
About 5% are squamous cell carcinomas or have adenosquamous differentiation. A
minority may show carcinoid or a variety of mesenchymal features
(carcinosarcoma). Papillary tumors generally have a better prognosis than other
tumors. By the time these neoplasms are discovered, most have invaded the liver
centrifugally, and many have extended to the cystic duct and adjacent bile ducts
and portal-hepatic lymph nodes. The peritoneum, gastrointestinal tract, and lungs
are common sites of seeding.
CONTROL QUESTIONS
1. The role of the liver in the functioning of the organism. Characteristics of
the main groups of pathological processes in the liver. Classification.
Epidemiology.
2. Hepatitis. Definition. Classification principles: the current, etiology, origin
and morphology.
3. Viral hepatitis:
a) characteristics of the etiological factors (A, B, C, D-type virus). Priority
ways of infection. Pathogenesis. The morphological changes in the liver:
morphological cytolysis, cell reactions, the bile production and biliary
excretion,
b) morphology of acute viral hepatitis: acute cyclic form, form with massive
necrosis, pericholangiolitic form. Outcomes,
c) morphological manifestations of chronic hepatitis, pathogenesis,
outcomes.
4. Alcoholic liver disease. Alcoholic fatty liver. Alcoholic hepatitis. Alcoholic
cirrhosis. Epidemiology, pathogenesis, morphogenesis, morphological
5.
6.
7.
8.
9.
characteristics, clinical manifestations, complications and causes of death,
outcomes, prognosis.
Hepatosis. Definition. Etiology. Pathogenesis. The acute toxic degeneration
of the liver. Meaning of sensitization in its development. Period of yellow
and red dystrophy. Outcomes. Causes of death.
Chronic steatosis. Reasons. Clinical and morphological manifestations.
Outcomes.
Cirrhosis. Definition. Etiology. Pathogenesis. Classification principles.
a) pathological anatomy of postnecrotic, portal, biliary and mixed cirrhosis.
b) the major complications of portal hypertension and
hepatic
(hepatocellular) failure. Hepatic encephalopathy. Icterus. Renal failure.
Ascites and edema. Endocrine disorders. Circulatory disorders and
infectious complications. Pathogenesis, clinical and morphological
characteristics.
Hepatic tumors. Benign and malignant neoplasms. Epidemiology.
Histogenesis. Macro- and microscopic picture. Regularities metastasis.
Cholecystitis, cholangitis. Ways of infection. Meaning of the stones in the
development of cholecystitis. Types of acute cholecystitis (catarrhal,
purulent, gangrenous). Chronic cholecystitis. Morphology. Complications.
Tumors and congenital anomalies of biliary tract. Classification. Clinical
and morphological characteristics.
The practical part of the subject:
Slides: In the study micropreparations pay attention to the education
elements, designated by the letters in parentheses.
1. Hepatitis. H & E stain. In the hepatic parenchyma are observed hydropic
degeneration (a), necrosis of hepatocytes (b) with the presence of
Councilman’s body (c), hyperemia of vessels and edema of the stroma (d).
In the portal tracts are observed diffuse lymphohistiocytic infiltration (e),
hyperplasia of stellate reticuloendotheliocytes (Kupffer’s cells).
2. Steatosis. Stain Sudan III. Fatty degeneration and necrosis of hepatocytes
(a), in the stroma - cellular reaction and proliferation of connective
tissue (b).
3. Toxic liver degeneration. H & E stain. The structure of hepatic lobules
changed, hepatocytes in the center of the lobules is in a state of fatty
degeneration and necrosis (a), on the periphery of the lobules hepatocytes
with signs of reparative regeneration (b). Newly formed bile ducts
determined (c).
4. Postnecrotic cirrhosis. H & E stain. Hepatocytes is in a state fatty
degeneration and necrosis (a). There is a violation of the trabecular structure
of the liver and the formation of false lobules (nodes regenerates) (b),
between which proliferation of connective tissue are observed (c). Portal
triads close together and with the central veins (d). Proliferating bile ducts
(e) and lympho-macrophage infiltration (f) are observed.
5. Biliary cirrhosis (secondary). H & E stain. In the central parts of liver
lobules are observed the focal necrosis of hepatocytes (a) and periportal
necrosis with the formation of "bile lakes" (b). Around nodes- regenerators
(c) are observed proliferation of connective tissue that connects the central
and portal zones of lobules (d). Bile capillaries expanded with signs of
cholestasis (e).
6. Muscat cirrhosis. H & E stain. In the center of hepatic lobule stagnant
hyperemia (a), fatty degeneration and necrosis of hepatocytes (b), in
peripheral parts - hypertrophied hepatocytes (c). Around nodes- regenerates
(d) and in the portal tracts are observed proliferation of connective tissue,
the compound of the central vein with portal fields (e).
macropreparations:
1. Postnecrotic cirrhosis: the liver is greatly reduced in size, yellowish gray color,
in the surface are observed large hillocks. Consistency liver is dense. On the cut
organ have the nodular structure in a spherical form foci of various sizes, up to 3
cm in diameter. Between nodes – regenerates are observed wide layer of fibrous
tissue. Reasons: acute toxic degeneration of the liver, viral hepatitis with massive
necrosis,
chronic
hepatitis
high
activity,
hepatotoxic
poisons.
Complications: hepatocellular insufficiency - hepatic encephalopathy, jaundice,
hemorrhagic syndrome, hormonal disorders, hepatorenal syndrome, dyspepsia;
hepatocellular carcinoma. Outcome: hepatocellular insufficiency.
2. Muscat cirrhosis: the liver is reduced in size, in the surface are observed small
hillocks, dense texture. On the cut on the background of diffuse nodes regenerates
with narrow interlayers of connective tissue, is determined mottled parenchyma in
the form of reddish inclusions. Reasons: Chronic heart failure, chronic venous
stasis in the systemic circulation. Complications: the syndrome of portal
hypertension, ascites, splenomegaly, varicose portocaval anastomosis, bleeding,
anemia. Outcome: portal hypertension.
3. Biliary cirrhosis (secondary): liver slightly enlarged, light brown color with
green blotches, surface is small hilly, texture is dense, on the cut - structure of the
parenchyma nodular structure, divided by gray narrow interlayers of fibrous tissue.
Bile ducts are dilated, filled with bile.
Reasons: blockage of the large bile ducts - gallstone disease, inflammatory
narrowing (stricture) of the biliary tract, primary and metastatic tumors
gepatopankreoduodenalnoy zone, parasitic diseases of the liver and biliary tract
(hydatid disease, ascariasis, opistorhoz), congenital biliary atresia, cyst ducts less
sclerosing cholangitis. Complications: pneumonia, abscess formation, sepsis.
Outcome: hepatocellular insufficiency.
4. Multiple liver abscesses: liver slightly enlarged, on the cut in the subcapsular
parenchyma there are multiple pathological foci round shape, different sizes,
containing pus. Reasons: purulent destructive cholangitis and cholangiolitis.
Complications: jaundice, hepatic failure. Outcome: unfavorable, pyosepticemia.
5. Gallstones: the gall bladder enlarged in size, on the serosa have gray-white
imposing of fibrin with the organization. On the cut on the wall of gall bladder is
thickened to 0,8 mm, the mucous membrane is smoothed. The lumen of the gall
bladder has multiple stones, smooth, green-brown. The stones are located
compactly. Complications: of perforation, abscess and gangrenous cholecystitis,
peritonitis, jaundice. Outcome: determined complications.
Test control
Select one or more correct answers
1. Morphological basis of hepatosis
1) degeneration of hepatocytes
2) necrosis of hepatocytes
3) inflammation in the liver
4) pylephlebitis
2. Morphological signs of toxic hepatic dystrophy
1) reducing the size of the liver
2) imposing of fibrin on the capsule
3) extensive necrosis of hepatocytes
4) grainy surface
5) increase the size of the liver
6) the flabby consistency of liver
3. Outcomes of toxic hepatic dystrophy
1) Portal cirrhosis
2) Postnecrotic cirrhosis
3)Biliary cirrhosis
4) Muscat cirrhosis
4. CAUSES OF steatosis
1) poor quality food poisoning
2) Alcohol
3) mushroom poisoning
4) diabetes
5) viral hepatitis
5. PRIMARY HEPATITIS
1) septic hepatitis
2) drug-induced hepatitis
3) alcoholic hepatitis
4) Viral Hepatitis
5) tuberculous hepatitis
6. Signs of chronic persistent forms of viral hepatitis "B"
1) stored lobular structure
2) periportal fibrosis
3) infiltration in the portal tracts
4) expressed cholestasis
5) apoptotic Mallory’s bodies
7. Signs of chronic viral hepatitis "C"
1) macrovesicular steatosis of hepatocytes
2) the formation of lymphoid follicles in the portal tracts
3) confluent and bridging necrosis of hepatocytes
4) apoptotic Councilman’s bodies
5) expansion of portal tracts due to fibrosis
8. Signs of acute alcoholic hepatitis
1) fatty degeneration of hepatocytes
2) leukocyte infiltration
3) the presence of cells Mallory
4) the formation of Councilman’s bodies
5) focal necrosis of individual hepatocytes
9. Chronic viral hepatitis develop after
1) Hepatitis "B"
2) hepatitis "C"
3) Hepatitis "A"
4) the combined hepatitis "B" and «D»
5) Hepatitis "E"
10. Cirrhosis can be caused by
1) a fulminant hepatitis
2) diabetes
3) purulent osteomyelitis
4) the alimentary protein deficiency
5) alcoholism
11.Morphological signs of postnecrotic cirrhosis
1) the approach of portal triads with each other and the central veins
2) degeneration and necrosis of hepatocytes
3) lympho-macrophage infiltration
4) leukocyte infiltration
5) cholangitis, cholestasis
12.Morphological signs of portal cirrhosis
1) small tuberosity of liver
2) wide connective field
3) fine-meshed network of connective tissue in the lobules
4) early hepatic failure
5) early portal hypertension
13.Histological features of primary biliary cirrhosis
1) granulomatous cholangitis
2) decrease in the number of bile ducts
3) infiltration of portal tracts
4) expansion of portal tracts due to fibrosis
14.SECONDARY biliary cirrhosis is characterized by
1) in the surface large hillocks
2) liver dark green color
3) bile stasis
4) in the surface small hillocks
5) associated with progressive massive hepatic necrosis
6) associated with obstruction of extrahepatic bile ducts
15.SIGNS hepatocellular insufficiency
1) hyperalbuminemia
2) icterus
3) encephalopathy
4) hepatorenal syndrome
5) coagulopathy
16.General factors of stone formation
1) violation of the osmotic pressure
2) violation of protein metabolism
3) violation of mineral metabolism
4) avitaminoses
5) increase in blood viscosity
17.Histological signs of acute cholecystitis
1) neutrophilic infiltration of the bladder wall
2) sclerosis of the bladder wall
3) lymphoid infiltration of the bladder
4) necrosis of the bladder wall
5) imposition of fibrin on the mucous
18.Histological signs of chronic cholecystitis
1) atrophy of the mucosa
2) sclerosis of the bladder wall
3) lymphoid infiltration of the bladder
4) necrosis of the bladder wall
5) imposition of fibrin on the mucous
19. Histological forms of gallbladder cancer
1) scirrhus
2) adenocarcinoma
3) epidermal cancer
4) mucosal cancer
20. Histological forms of liver cancer
1) hepatocellular carcinoma
2) cholangiocellular cancer
3) anaplastic cancer
4) small cell cancer
21. The cause of death of patients with cirrhosis
1) pulmonary embolism
2) hepatocellular insufficiency
3) complications of portal hypertension
4) hepatocellular carcinoma
5) secondary bacterial infection
ORENBURG STATE MEDICAL UNIVERSITY
DEPARTMENT OF PATHOLOGICAL ANATOMY
METHODICAL MANUAL FOR PRACTICAL TRAINING FOR STUDENTS OF
FOREIGN FACULTY
THEME:
HEART DISEASE. Valvular Heart Disease. Myocardial disease. Diseases of the
pericardium. Rheumatism. Congenital Heart Disease.
HEART DISEASE. Valvular Heart Disease. Myocardial disease. Diseases of the
pericardium. Rheumatism. Congenital Heart Disease.
Valvular Heart Disease
Valvular disease can come to clinical attention due to stenosis, insufficiency
(regurgitation or incompetence), or both.
Valvular abnormalities may be congenital (discussed earlier) or acquired. Acquired
stenoses of the aortic and mitral valves account for approximately two thirds of all
cases of valve disease. Valvular stenosis is almost always due to a chronic
abnormality of the valve cusp that becomes clinically evident after many years.
Relatively few disorders produce valvular stenosis.
The causes of acquired heart valve diseases are summarized in Table 1 and
discussed in the following sections. The most frequent causes of the major
functional valvular lesions are:
•
Aortic stenosis: calcification of anatomically normal and congenitally
bicuspid aortic valves
•
Aortic insufficiency: dilation of the ascending aorta, usually related to
hypertension and aging
•
•
Mitral stenosis: rheumatic heart disease
Mitral insufficiency: myxomatous degeneration (mitral valve prolapse)
TABLE 1 -- Major Etilogies of Acquired Heart Valve Disease
Mitral Valve Disease
Aortic Valve Disease
MITRAL STENOSIS
AORTIC STENOSIS
Postinflammatory scarring
(rheumatic heart disease)
Postinflammatory scarring
(rheumatic heart disease)
Senile calcific aortic stenosis
Calcification of congenitally
deformed valve
MITRAL REGURGITATION
AORTIC REGURGITATION
Abnormalities of Leaflets and Commissures
Postinflammatory scarring
Postinflammatory scarring
(rheumatic heart disease)
Infective endocarditis
Infective endocarditis
Mitral valve prolapse
Marfan syndrome
Drugs (e.g., fen-phen)
Abnormalities of Tensor Apparatus Aortic Disease
Rupture of papillary muscle
Degenerative aortic dilation
Papillary muscle dysfunction
(fibrosis)
Syphilitic aortitis
Rupture of chordae tendineae
Ankylosing spondylitis
Rheumatoid arthritis
Marfan syndrome
Abnormalities of Left Ventricular Cavity and/or Annulus
LV enlargement (myocarditis, dilated cardiomyopathy)
Calcification of mitral ring
LV, Left ventricular.
Calcific Aortic Stenosis
The most common of all valvular abnormalities, acquired aortic stenosis, is usually
the consequence of age-associated “wear and tear” of either anatomically normal
valves or congenitally bicuspid valves.
Morphology. The morphologic hallmark of nonrheumatic, calcific aortic stenosis
(with either tricuspid or bicuspid valves) is heaped-up calcified masses within the
aortic cusps that ultimately protrude through the outflow surfaces into the sinuses
of Valsalva, preventing the opening of the cusps. The free edges of the cusps are
usually not involved. The calcific process begins in the valvular fibrosa, at the
points of maximal cusp flexion (near the margins of attachment). Microscopically,
the layered architecture of the valve is largely preserved. An earlier,
hemodynamically inconsequential stage of the calcification process is called aortic
valve sclerosis. In aortic stenosis the functional valve area is decreased sufficiently
by large nodular calcific deposits to cause measurable obstruction to outflow; this
subjects the left ventricular myocardium to progressively increasing pressure
overload.
In contrast to rheumatic (and congenital) aortic stenosis , commissural fusion is not
usually seen. The mitral valve is generally normal, although some patients may
have direct extension of aortic valve calcific deposits onto the anterior mitral
leaflet. In contrast, virtually all patients with rheumatic aortic stenosis also have
concomitant and characteristic structural abnormalities of the mitral valve.
Mitral Annular Calcification
Degenerative calcific deposits can develop in the peripheral fibrous ring (annulus)
of the mitral valve. Grossly, these appear as irregular, stony hard, occasionally
ulcerated nodules (2–5 mm in thickness) that lie behind the leaflets . The process
generally does not affect valvular function or otherwise become clinically
important. In unusual cases, however, mitral annular calcification may lead to (1)
regurgitation by interfering with physiologic contraction of the valve ring, (2)
stenosis by impairing opening of the mitral leaflets, or (3) arrhythmias and
occasionally sudden death by penetration of calcium deposits to a depth sufficient
to impinge on the atrioventricular conduction system. Because calcific nodules
may also provide a site for thrombi that can embolize, patients with mitral annular
calcification have an increased risk of stroke, and the calcific nodules can also be
the nidus for infective endocarditis. Heavy calcific deposits are sometimes
visualized on echocardiography or seen as a distinctive, ringlike opacity on chest
radiographs. Mitral annular calcification is most common in women over age 60
and individuals with mitral valve prolapse (see below) or elevated left ventricular
pressure (as in systemic hypertension, aortic stenosis, or hypertrophic
cardiomyopathy).
MITRAL VALVE PROLAPSE (MYXOMATOUS DEGENERATION OF
THE MITRAL VALVE)
In mitral valve prolapse (MVP), one or both mitral valve leaflets are “floppy” and
prolapse, or balloon back, into the left atrium during systole. The key histologic
change in the tissue is called myxomatous degeneration. MVP affects
approximately 3% of adults in the United States; it is most often an incidental
finding on physical examination (particularly in young women), but in a small
minority of affected individuals may lead to serious complications.
Morphology. The characteristic anatomic change in MVP is interchordal
ballooning (hooding) of the mitral leaflets or portions thereof . The affected leaflets
are often enlarged, redundant, thick, and rubbery. The associated tendinous cords
may be elongated, thinned, or even ruptured, and the annulus may be dilated. The
tricuspid, aortic, or pulmonary valves may also be affected. Histologically, there is
attenuation of the collagenous fibrosa layer of the valve, on which the structural
integrity of the leaflet depends, accompanied by marked thickening of the
spongiosa layer with deposition of mucoid (myxomatous) material . Secondary
changes reflect the stresses and injury incident to the billowing leaflets: (1) fibrous
thickening of the valve leaflets, particularly where they rub against each other; (2)
linear fibrous thickening of the left ventricular endocardial surface where the
abnormally long cords snap or rub against it; (3) thickening of the mural
endocardium of the left ventricle or atrium as a consequence of friction-induced
injury induced by the prolapsing, hyper-mobile leaflets; (4) thrombi on the atrial
surfaces of the leaflets or the atrial walls; and (5) focal calcifications at the base of
the posterior mitral leaflet. Mild myxomatous degeneration can also occur in mitral
valves secondary to regurgitation of other etiologies (e.g., ischemic dysfunction).
RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE
Rheumatic fever (RF) is an acute, immunologically mediated, multisystem
inflammatory disease that occurs a few weeks after an episode of group A
streptococcal pharyngitis. Acute rheumatic carditis is a frequent manifestation
during the active phase of RF and may progress over time to chronic rheumatic
heart disease (RHD), of which valvular abnormalities are key manifestations.
RHD is characterized principally by deforming fibrotic valvular disease,
particularly mitral stenosis, of which it is virtually the only cause. The incidence
and mortality rate of RF and RHD have declined remarkably in many parts of the
world over the past century, as a result of improved socioeconomic conditions and
rapid diagnosis and treatment of streptococcal pharyngitis. Nevertheless, in
developing countries, and in many crowded, economically depressed urban areas
in the Western world, RHD remains an important public health problem, affecting
an estimated 15 million people. Rheumatic fever only rarely follows infections by
streptococci at other sites, such as the skin.
Morphology. During acute RF, focal inflammatory lesions are found in various
tissues. Distinctive lesions occur in the heart, called Aschoff bodies, which consist
of foci of lymphocytes (primarily T cells), occasional plasma cells, and plump
activated macrophages called Anitschkow cells (pathognomonic for RF). These
macrophages have abundant cytoplasm and central round-toovoid nuclei in which
the chromatin is disposed in a central, slender, wavy ribbon (hence the designation
“caterpillar cells”), and may become multinucleated.
During acute RF, diffuse inflammation and Aschoff bodies may be found in any of
the three layers of the heart, causing pericarditis, myocarditis, or endocarditis
(pancarditis).
Inflammation of the endocardium and the left-sided valves typically results in
fibrinoid necrosis within the cusps or along the tendinous cords. Overlying these
necrotic foci are small (1- to 2-mm) vegetations, called verrucae, along the lines
of closure. These vegetations place RHD within a small group of disorders that are
associated with vegetative valve disease, each with its own characteristic
morphologic features . Subendocardial lesions, perhaps exacerbated by regurgitant
jets, may induce irregular thickenings called MacCallum plaques, usually in the
left atrium. The cardinal anatomic changes of the mitral valve in chronic RHD are
leaflet thickening, commissural fusion and shortening, and thickening and
fusion of the tendinous cords . In chronic disease the mitral valve is virtually
always involved. The mitral valve is affected alone in 65% to 70% of cases, and
along with the aortic valve in another 25% of cases. Tricuspid valve involvement is
infrequent, and the pulmonary valve is only rarely affected. Because of the
increase in calcific aortic stenosis (see earlier) and the reduced frequency of RHD,
rheumatic aortic stenosis now accounts for less than 10% of cases of acquired
aortic stenosis. Fibrous bridging across the valvular commissures and calcification
create “fish mouth” or “buttonhole” stenoses. With tight mitral stenosis, the left
atrium progressively dilates and may harbor mural thrombi in the appendage or
along the wall, either of which can embolize. Long-standing congestive changes in
the lungs may induce pulmonary vascular and parenchymal changes and in time
lead to right ventricular hypertrophy. The left ventricle is largely unaffected by
isolated pure mitral stenosis. Microscopically, in the mitral leaflets there is
organization of the acute inflammation and subsequent diffuse fibrosis and
neovascularization that obliterate the originally layered and avascular leaflet
architecture. Aschoff bodies are rarely seen in surgical specimens or autopsy tissue
from patients with chronic RHD, as a result of the long times between the initial
insult and the development of the chronic deformity.
Pathogenesis.
Acute rheumatic fever results from immune responses to group A streptococci,
which happen to cross-react with host tissues. Antibodies directed against the M
proteins of streptococci have been shown to cross-react with self antigens in the
heart. In addition, CD4+ T cells specific for streptococcal peptides also react with
self proteins in the heart, and produce cytokines that activate macrophages (such as
those found in Aschoff bodies). Damage to heart tissue may thus be caused by a
combination of antibody- and T cell–mediated reactions.
Acute RF typically appears 10 days to 6 weeks after an episode of pharyngitis
caused by group A streptococci in about 3% of infected patients. It occurs most
often in children between ages 5 and 15, but first attacks can occur in middle to
later life. Although pharyngeal cultures for streptococci are negative by the time
the illness begins, antibodies to one or more streptococcal enzymes, such as
streptolysin O and DNase B, can be detected in the sera of most patients with RF.
The predominant clinical manifestations are carditis and arthritis, the latter more
common in adults than in children. Clinical features related to acute carditis
include pericardial friction rubs, weak heart sounds, tachycardia, and arrhythmias.
Myocarditis may cause cardiac dilation that can evolve to functional mitral valve
insufficiency or even heart failure. Approximately 1% of patients die from
fulminant RF. Arthritis typically begins with migratory polyarthritis (accompanied
by fever) in which one large joint after another becomes painful and swollen for a
period of days and then subsides spontaneously, leaving no residual disability.
After an initial attack there is increased vulnerability to reactivation of the disease
with subsequent pharyngeal infections, and the same manifestations are likely to
appear with each recurrent attack. Damage to the valves is cumulative.
Turbulence induced by ongoing valvular deformities begets additional fibrosis.
Clinical manifestations appear years or even decades after the initial episode of RF
and depend on which cardiac valves are involved. In addition to various cardiac
murmurs, cardiac hypertrophy and dilation, and heart failure, individuals with
chronic RHD may suffer from arrhythmias (particularly atrial fibrillation in the
setting of mitral stenosis), thromboembolic complications, and infective
endocarditis (see below). The long-term prognosis is highly variable. Surgical
repair or prosthetic replacement of diseased valves has greatly improved the
outlook for persons with RHD.
INFECTIVE ENDOCARDITIS
Infective endocarditis (IE) is a serious infection characterized by colonization or
invasion of the heart valves or the mural endocardium by a microbe. This leads to
the formation of vegetations composed of thrombotic debris and organisms, often
associated with destruction of the underlying cardiac tissues. The aorta,
aneurysmal sacs, other blood vessels, and prosthetic devices can also become
infected. Although fungi and other classes of microorganisms can be responsible,
most cases are caused by bacterial infections (bacterial endocarditis). Prompt
diagnosis and effective treatment of IE is important.
Traditionally, IE has been classified on clinical grounds into acute and subacute
forms. This subdivision reflects the range of the disease severity and tempo, which
are determined in large part by the virulence of the infecting microorganism and
whether underlying cardiac disease is present. Acute infective endocarditis is
typically caused by infection of a previously normal heart valve by a highly
virulent organism that produces necrotizing, ulcerative, destructive lesions. These
infections are difficult to cure with antibiotics and usually require surgery. Death
within days to weeks ensues in many patients with acute IE, despite treatment. In
contrast, in subacute IE, the organisms are of lower virulence. These organisms
cause insidious infections of deformed valves that are less destructive. In such
cases the disease may pursue a protracted course of weeks to months, and cures are
often produced with antibiotics.
Etiology and Pathogenesis.
As mentioned above, IE can develop on previously normal valves, especially with
highly virulent organisms, but a variety of cardiac and vascular abnormalities
predispose to this form of infection. In years past, rheumatic heart disease was the
major antecedent disorder, but more common now are mitral valve prolapse,
degenerative calcific valvular stenosis, bicuspid aortic valve (whether calcified or
not), artificial (prosthetic) valves, and unrepaired and repaired congenital defects.
The causative organisms differ somewhat in the major high-risk groups.
Endocarditis of native but previously damaged or otherwise abnormal valves is
caused most commonly (50% to 60% of cases) by Streptococcus viridans, which is
part of the normal flora of the oral cavity. In contrast, more virulent S. aureus
organisms commonly found on the skin can infect either healthy or deformed
valves and are responsible for 10% to 20% of cases overall; S. aureus is the major
offender in intravenous drug abusers with IE. The roster of the remaining bacteria
includes enterococci and the so-called HACEK group (Haemophilus,
Actinobacillus, Cardiobacterium, Eikenella, and Kingella), all commensals in the
oral cavity. Prosthetic valve endocarditis is caused most commonly by coagulasenegative staphylococci (e.g., S. epidermidis). Other agents causing endocarditis
include gram-negative bacilli and fungi. In about 10% to 15% of all cases of
endocarditis, no organism can be isolated from the blood (“culture-negative”
endocarditis).
Foremost among the factors predisposing to the development of endocarditis are
those that lead to bacteremia. The source of the organism may be an obvious
infection elsewhere, a dental or surgical procedure, a contaminated needle shared
by intravenous drug users, or seemingly trivial breaks in the epithelial barriers of
the gut, oral cavity, or skin. The risk can be lowered in those with predisposing
factors (e.g., valve abnormalities, conditions causing bacteremia) by prophylaxis
with antibiotics.
Morphology. The hallmark of IE is the presence of friable, bulky, potentially
destructive vegetations containing fibrin, inflammatory cells, and bacteria or other
organisms on the heart valves . The aortic and mitral valves are the most common
sites of infection, although the valves of the right heart may also be involved,
particularly in intravenous drug abusers. The vegetations may be single or multiple
and may involve more than one valve. Vegetations sometimes erode into the
underlying myocardium and produce an abscess (ring abscess). Emboli may be
shed from the vegetations at any time; because the embolic fragments may contain
large numbers of virulent organisms, abscesses often develop at the sites where the
emboli lodge, leading to sequelae such as septic infarcts or mycotic aneurysms.
The vegetations of subacute endocarditis are associated with less valvular
destruction than those of acute endocarditis, although the distinction between the
two forms may blur. Microscopically, the vegetations of typical subacute IE often
have granulation tissue indicative of healing at their bases. With time, fibrosis,
calcification, and a chronic inflammatory infiltrate can develop.
NONINFECTED VEGETATIONS
Noninfected (sterile) vegetations are caused by nonbacterial thrombotic
endocarditis and the endocarditis of systemic lupus erythematosus (SLE), called
Libman-Sacks endocarditis.
Nonbacterial Thrombotic Endocarditis (NBTE)
NBTE is characterized by the deposition of small sterile thrombi on the leaflets of
the cardiac valves . The lesions are 1 mm to 5 mm in size, and occur singly or
multiply along the line of closure of the leaflets or cusps. Histologically they are
composed of bland thrombi that are loosely attached to the underlying valve. The
vegetations are not invasive and do not elicit any inflammatory reaction. Thus, the
local effect of the vegetations is usually unimportant, but they may be the source of
systemic emboli that produce infarcts in the brain, heart, or elsewhere.
NBTE is often encountered in debilitated patients, such as those with cancer or
sepsis—hence the previously used term marantic endocarditis. It frequently occurs
concomitantly with deep venous thromboses, pulmonary emboli, or other findings
consistent with an underlying systemic hypercoagulable state . Indeed, there is a
striking association with mucinous adenocarcinomas, which may relate to the
procoagulant effects of tumor-derived mucin or tissue factor, and NBTE can be a
part of the Trousseau syndrome of migratory thrombophlebitis . Endocardial
trauma, as from an indwelling catheter, is another well-recognized predisposing
condition, and right-sided valvular and endocardial thrombotic lesions frequently
track along the course of Swan-Ganz pulmonary artery catheters.
Endocarditis of Systemic Lupus Erythematosus (Libman-Sacks Disease)
Mitral and tricuspid valvulitis with small, sterile vegetations, called Libman-Sacks
endocarditis, is occasionally encountered in SLE. The lesions are small (1–4 mm
in diameter) single or multiple, sterile, pink vegetations that often have a warty
(verrucous) appearance. They may be located on the undersurfaces of the
atrioventricular valves, on the valvular endocardium, on the chords, or on the
mural endocardium of atria or ventricles. Histologically the vegetations consist of a
finely granular, fibrinous eosinophilic material that may contain hematoxylin
bodies, homogeneous remnants of nuclei damaged by anti-nuclear antigen bodies .
An intense valvulitis may be present, characterized by fibrinoid necrosis of the
valve substance that is often contiguous with the vegetation. Active leaflet
vegetations can be difficult to distinguish from those of infective endocarditis ;
fibrosis and serious deformities can result that resemble chronic rheumatoid heart
disease and require surgery.
Thrombotic heart valve lesions with sterile vegetations or rarely fibrous thickening
commonly occur with the antiphospholipid syndrome , which you will recall can
also lead to a hypercoagulable state.The mitral valve is more frequently involved
than the aortic valve; regurgitation is the usual functional abnormality.
CARCINOID HEART DISEASE
Carcinoid heart disease is the cardiac manifestation of the systemic syndrome
caused by carcinoid tumors. It generally involves the endocardium and valves of
the right heart. Cardiac lesions are present in one half of patients with the carcinoid
syndrome, which is characterized by episodic flushing of the skin, cramps, nausea,
vomiting, and diarrhea .
Morphology. The cardiovascular lesions associated with the carcinoid syndrome
are distinctive, consisting of firm plaquelike endocardial fibrous thickenings on the
inside surfaces of the cardiac chambers and the tricuspid and pulmonary valves;
occasionally they involve the major blood vessels of the right side, the inferior
vena cava and the pulmonary artery . The plaquelike thickenings are composed
predominantly of smooth muscle cells and sparse collagen fibers embedded in an
acid mucopolysaccharide-rich matrix material. Elastic fibers are not present in the
plaques. Structures underlying the plaques are intact.
Cardiomyopathies
The term cardiomyopathy (literally, heart muscle disease) is used to describe heart
disease resulting from an abnormality in the myocardium. Diseases of the
myocardium usually produce abnormalities in cardiac wall thickness and chamber
size, and mechanical and/or electrical dysfunction, and are associated with
significant morbidity and mortality. Although chronic myocardial dysfunction
secondary to ischemia, valvular abnormalities, or hypertension can cause
ventricular dysfunction (see previous sections of this chapter), these conditions are
not considered to be cardiomyopathies.
Cardiomyopathies of diverse etiology may have a similar morphologic
appearance, and a clinician encountering a person with myocardial disease is
usually unaware of the underlying cause. Hence the clinical approach is largely
determined by which one of three clinical, functional, and pathologic patterns is
present: (1) dilated cardiomyopathy (DCM), (2) hypertrophic cardiomyopathy
(HCM), or (3) restrictive cardiomyopathy.
DILATED CARDIOMYOPATHY
The term dilated cardiomyopathy (DCM) is applied to a form of cardiomyopathy
characterized by progressive cardiac dilation and contractile (systolic)
dysfunction, usually with concomitant hypertrophy. It is sometimes called
congestive cardiomyopathy.
Morphology. In DCM the heart is usually enlarged, heavy (often weighing two to
three times normal), and flabby, due to dilation of all chambers . Mural thrombi are
common and may be a source of thromboemboli. There are no primary valvular
alterations, and mitral (or tricuspid) regurgitation, when present, results from left
(or right) ventricular chamber dilation (functional regurgitation). Either the
coronary arteries are free of significant narrowing or the obstructions present are
insufficient to explain the degree of cardiac dysfunction.
The histologic abnormalities in DCM are nonspecific and usually do not point
to a specific etiologic agent. Moreover, the severity of morphologic changes may
not reflect either the degree of dysfunction or the patient's prognosis. Most muscle
cells are hypertrophied with enlarged nuclei, but some are attenuated, stretched,
and irregular. Interstitial and endocardial fibrosis of variable degree is present, and
small subendocardial scars may replace individual cells or groups of cells,
probably reflecting healing of previous ischemic necrosis of myocytes caused by
hypertrophy-induced imbalance between perfusion and demand.
HYPERTROPHIC CARDIOMYOPATHY
Hypertrophic cardiomyopathy (HCM) is characterized by myocardial hypertrophy,
poorly compliant left ventricular myocardium leading to abnormal diastolic filling,
and in about one third of cases, intermittent ventricular outflow obstruction. It is
the leading cause of left ventricular hypertrophy unexplained by other clinical or
pathologic causes. As discussed below, HCM is caused by mutations in genes
encoding sarcomeric proteins. Since the incidence of unexplained cardiac
hypertrophy is approximately 1 in 500, HCM may be the most common
cardiovascular disorder caused by single gene mutations. The heart is thick-walled,
heavy, and hypercontracting, in striking contrast to the flabby, hypocontracting
heart of DCM. HCM causes primarily diastolic dysfunction; systolic function is
usually preserved. The two most common diseases that must be distinguished
clinically from HCM are deposition diseases of the heart (e.g., amyloidosis,
Fabry's disease) and hypertensive heart disease coupled with age-related subaortic
septal hypertrophy (see “Hypertensive Heart Disease”). Occasionally, valvular or
congenital subvalvular aortic stenosis can also mimic HCM.
Morphology. The essential feature of HCM is massive myocardial hypertrophy,
usually without ventricular dilation ( Fig. 12-35 ). The classic pattern is
disproportionate thickening of the ventricular septum as compared with the free
wall of the left ventricle (with a ratio greater than 1 : 3), frequently termed
asymmetric septal hypertrophy. In about 10% of cases, however, the hypertrophy
is symmetrical throughout the heart. On cross-section, the ventricular cavity loses
its usual round-to-ovoid shape and may be compressed into a “banana-like”
configuration by bulging of the ventricular septum into the lumen ( Fig. 12-35A ).
Although marked hypertrophy can involve the entire septum, it is usually most
prominent in the subaortic region. Often present are endocardial thickening or
mural plaque formation in the left ventricular outflow tract and thickening of the
anterior mitral leaflet. Both findings are a result of contact of the anterior mitral
leaflet with the septum during ventricular systole, and they correlate with
echocardiographically demonstrated functional left ventricular outflow tract
obstruction during midsystole.
The most important histologic features of the myocardium in HCM are (1)
extensive myocyte hypertrophy to a degree unusual in other conditions, with
transverse myocyte diameters frequently greater than 40 μm (normal, ∼15 μm); (2)
haphazard disarray of bundles of myocytes, individual myocytes, and contractile
elements in sarcomeres within cells (termed myofiber disarray); and (3)
interstitial and replacement fibrosis.
RESTRICTIVE CARDIOMYOPATHY
Restrictive cardiomyopathy is a disorder characterized by a primary decrease in
ventricular compliance, resulting in impaired ventricular filling during diastole.
Because the contractile (systolic) function of the left ventricle is usually
unaffected, the functional abnormality can be confused with that of constrictive
pericarditis or HCM. Restrictive cardiomyopathy may be idiopathic or associated
with distinct diseases or processes that affect the myocardium, principally radiation
fibrosis, amyloidosis, sarcoidosis, metastatic tumors, or the deposition of
metabolites that accumulate due to inborn errors of metabolism.
Morphology. The ventricles are of approximately normal size or slightly enlarged,
the cavities are not dilated, and the myocardium is firm and noncompliant. Biatrial
dilation is commonly observed. Microscopically, there may be only patchy or
diffuse interstitial fibrosis, which can vary from minimal to extensive. However,
endomyocardial biopsy will often reveal a specific etiology. An important specific
subgroup is amyloidosis (described later).
Several other restrictive conditions require brief mention.
Endomyocardial fibrosis is principally a disease of children and young adults in
Africa and other tropical areas, characterized by fibrosis of the ventricular
endocardium and subendocardium that extends from the apex upward, often
involving the tricuspid and mitral valves. The fibrous tissue markedly diminishes
the volume and compliance of affected chambers and so induces a restrictive
functional defect. Ventricular mural thrombi sometimes develop, and indeed there
is a suggestion that the fibrous tissue results from the organization of mural
thrombi. The etiology is unknown.
Loeffler endomyocarditis also results in endomyocardial fibrosis, typically with
large mural thrombi. It is similar in morphology to the tropical disease, but in
addition to the cardiac changes, there is often a peripheral eosinophilia (i.e.,
elevated blood eosinophils) and eosinophilic infiltrates in other organs. The release
of toxic products of eosinophils, especially major basic protein, is postulated to
initiate endomyocardial necrosis, followed by scarring of the necrotic area,
layering of the endocardium by thrombus, and finally organization of the
thrombus.
Endocardial fibroelastosis is an uncommon heart disease of obscure etiology
characterized by focal or diffuse fibroelastic thickening usually involving the
mural left ventricular endocardium. It is most common in the first 2 years of life,
and is accompanied by aortic valve obstruction or other congenital cardiac
anomalies in about one third of cases. Diffuse involvement may be responsible for
rapid and progressive cardiac decompensation and death.
MYOCARDITIS
Under the designation myocarditis are a diverse group of pathologic entities in
which infectious microorganisms and/or an inflammatory process cause
myocardial injury. These disorders must be distinguished from conditions, such as
ischemic heart disease, in which injuries caused by other mechanisms lead to
inflammation secondarily.
Etiology and Pathogenesis.
In the United States, viral infections are the most common cause of myocarditis.
Coxsackieviruses A and B and other enteroviruses probably account for most of the
cases. Other less common etiologic agents include cytomegalovirus, HIV, and a
host of other agents . The responsible virus can sometimes be identified by
serologic studies or, more recently, identification of viral nucleic acids (DNA or
RNA) in myocardial biopsies. Whether viruses cause the myocardial injury directly
or initiate a destructive immune response is unclear.
Morphology. During the active phase of myocarditis the heart may appear normal
or dilated; some hypertrophy may be present depending on disease duration. In
advanced stages the ventricular myocardium is flabby and often mottled by either
pale foci or minute hemorrhagic lesions. Mural thrombi may be present in any
chamber.
During active disease, myocarditis is most frequently characterized by an
interstitial inflammatory infiltrate associated with focal myocyte necrosis . A
diffuse, mononuclear, predominantly lymphocytic infiltrate is most common .
Although endomyocardial biopsies are diagnostic in some cases, they can be
spuriously negative because inflammatory involvement of the myocardium may be
focal or patchy. If the patient survives the acute phase of myocarditis, the
inflammatory lesions either resolve, leaving no residual changes, or heal by
progressive fibrosis.
Hypersensitivity myocarditis has interstitial infiltrates, principally perivascular,
composed of lymphocytes, macrophages, and a high proportion of eosinophils . A
morphologically distinctive form of myocarditis of uncertain cause, called giantcell myocarditis, is characterized by a widespread inflammatory cellular infiltrate
containing multinucleate giant cells interspersed with lymphocytes, eosinophils,
plasma cells, and macrophages. Focal to frequently extensive necrosis is present.
This variant carries a poor prognosis.
The myocarditis of Chagas disease is rendered distinctive by parasitization of
scattered myofibers by trypanosomes accompanied by an inflammatory infiltrate of
neutrophils, lymphocytes, macrophages, and occasional eosinophils .
Pericardial Disease
The most important pericardial disorders cause fluid accumulation, inflammation,
fibrous constriction, or some combination of these processes, usually in association
with disease elsewhere in the heart or a systemic disease; isolated pericardial
disease is unusual.[122]
PERICARDIAL EFFUSION AND HEMOPERICARDIUM
Normally, there are about 30 to 50 mL of thin, clear, straw-colored fluid in the
pericardial sac. Under various circumstances the parietal pericardium may be
distended by serous fluid (pericardial effusion), blood (hemopericardium), or pus
(purulent pericarditis). With long-standing pressure or volume overload, the
pericardium dilates. This permits a slowly accumulating pericardial effusion to
become quite large without interfering with cardiac function. Thus, with chronic
effusions of less than 500 mL in volume, the only clinical significance is a
characteristic globular enlargement of the heart shadow on chest radiographs. In
contrast, rapidly developing fluid collections of as little as 200 to 300 mL—for
example, due to hemopericardium caused by a ruptured MI or aortic dissection—
may produce compression of the thin-walled atria and venae cavae, or the
ventricles themselves. As a consequence, cardiac filling is restricted, producing
potentially fatal cardiac tamponade.
PERICARDITIS
Pericardial inflammation may occur secondary to a variety of cardiac diseases,
thoracic or systemic disorders, metastases from neoplasms arising in remote sites,
or a surgical procedure on the heart. Primary pericarditis is unusual and almost
always of viral origin. The major causes of pericarditis are listed in Table 2 . Most
evoke an acute pericarditis, but a few, such as tuberculosis and fungi, produce
chronic reactions.
TABLE 2 -- Causes of Pericarditis
INFECTIOUS AGENTS
Viruses
Pyogenic becteria
Tuberculosis
Fungi
Other parasites
PRESUMABLY IMMUNOLOGICALLY MEDIATED
Rheumatic fever
Systemic lupus erythematosus
Scleroderma
Postcardiotomy
Postmyocardial infarction (Dressler) syndrome
Drug hypersensitivity reaction
MISCELLANEOUS
Myocardial infarction
Uremia
Following cardiac surgery
Neoplasia
Trauma
Radiation
Acute Pericarditis
Serous Pericarditis.
This is characteristically produced by noninfectious inflammatory diseases, such as
rheumatic fever, SLE, and scleroderma, tumors, and uremia. An infection in the
tissues contiguous to the pericardium—for example, a bacterial pleuritis—may
incite sufficient irritation of the parietal pericardial serosa to cause a sterile serous
effusion that may progress to serofibrinous pericarditis and ultimately to a frank
suppurative reaction. In some instances a well-defined viral infection elsewhere—
upper respiratory tract infection, pneumonia, parotitis—antedates the pericarditis
and serves as the primary focus of infection. Infrequently, usually in young adults,
a viral pericarditis occurs as an apparent primary infection that may be
accompanied by myocarditis (myopericarditis). Histologically, there is a mild
inflammatory infiltrate in the epipericardial fat consisting predominantly of
lymphocytes. Organization into fibrous adhesions rarely occurs.
Fibrinous and Serofibrinous Pericarditis.
These two anatomic forms are the most frequent type of pericarditis and are
composed of serous fluid mixed with a fibrinous exudate. Common causes include
acute MI , the postinfarction (Dressler) syndrome (probably an autoimmune
condition appearing several weeks after an MI), uremia, chest radiation, rheumatic
fever, SLE, and trauma. A fibrinous reaction also follows routine cardiac surgery
Morphology. In fibrinous pericarditis the surface is dry, with a fine granular
roughening. In serofibrinous pericarditis a more intense inflammatory process
induces the accumulation of larger amounts of yellow to browen turbid fluid,
which is made brown and cloudy by the presence of leukocytes and red cells
(which may give the fluid a visibly bloody appearance), and often fibrin. As with
all inflammatory exudates, fibrin may be lysed with resolution of the exudate, or it
may become organized.
From the clinical standpoint the development of a loud pericardial friction rub is
the most striking characteristic of fibrinous pericarditis, and pain, systemic febrile
reactions, and signs suggestive of cardiac failure may be present. However, the
collection of serous fluid may sometimes prevent rubbing by separating the two
layers of the pericardium.
Purulent or Suppurative Pericarditis.
This form of pericarditis is caused by invasion of the pericardial space by
microbes, which may reach the pericardial cavity by several routes: (1) direct
extension from neighboring infections, such as an empyema of the pleural cavity,
lobar pneumonia, mediastinal infections, or extension of a ring abscess through the
myocardium or aortic root; (2) seeding from the blood; (3) lymphatic extension; or
(4) direct introduction during cardiotomy. Immunosuppression predisposes to
infection by all of these pathways. The exudate ranges from a thin cloudy fluid to
frank pus up to 400 to 500 mL in volume. The serosal surfaces are reddened,
granular, and coated with the exudate. Microscopically there is an acute
inflammatory reaction, which sometimes extends into surrounding structures to
induce mediastinopericarditis. Complete resolution is infrequent, and organization
by scarring is the usual outcome. The intense inflammatory response and the
subsequent scarring frequently produce constrictive pericarditis, a serious
consequence .
Hemorrhagic Pericarditis.
In this type of pericarditis the exudate is composed of blood mixed with a fibrinous
or suppurative effusion; it is most commonly caused by the spread of a malignant
neoplasm to the pericardial space. In such cases, cytologic examination of fluid
removed through a pericardial tap often reveals the presence of neoplastic cells.
Hemorrhagic pericarditis can also be found in bacterial infections, in persons with
an underlying bleeding diathesis, and in tuberculosis. Hemorrhagic pericarditis
often follows cardiac surgery and is occasionally responsible for significant blood
loss or even tamponade, requiring a “second-look” operation. The clinical
significance is similar to that of fibrinous or suppurative pericarditis.
Caseous Pericarditis.
This rare type of pericarditis is, until proved otherwise, tuberculous in origin;
infrequently, fungal infections evoke a similar reaction. Pericardial involvement
occurs by direct spread from tuberculous foci within the tracheobronchial nodes.
Caseous pericarditis is a frequent antecedent of disabling, fibrocalcific, chronic
constrictive pericarditis.
HEART DISEASE ASSOCIATED WITH RHEUMATOLOGIC
DISORDERS
Paradoxically, the prevalence and importance of cardiovascular manifestations of
rheumatologic diseases (including rheumatoid arthritis, SLE, systemic sclerosis,
ankylosing spondylitis, and psoriatic arthritis) has increased as a result of the
longer life expectancy of persons with these disorders and enhanced detection of
milder cases. Inflammatory mechanisms may cause vascular, myocardial, valvular,
and pericardial manifestations. In addition, ischemic heart disease seems to be
accelerated in individuals with inflammatory rheumatic conditions.
Rheumatoid arthritis is mainly a disorder of the joints, but it is also associated with
many extra-articular features (e.g., subcutaneous rheumatoid nodules, acute
vasculitis, and Felty syndrome. The heart is also involved in 20% to 40% of cases
of severe prolonged rheumatoid arthritis. The most common finding is a fibrinous
pericarditis that may progress to fibrous thickening of the visceral and parietal
pericardium and dense adhesions. Granulomatous rheumatoid nodules resembling
those that occur subcutaneously may also be identifiable in the myocardium. Much
less frequently, rheumatoid nodules involve the endocardium, valves of the heart,
and root of the aorta. Rheumatoid valvulitis can lead to marked fibrous thickening
and secondary calcification of the aortic valve cusps, producing changes
resembling those of chronic rheumatic valvular disease. The valvular lesions
associated with SLE were discussed previously under “Valvular Heart Disease.”
Congenital Heart Disease
Congenital heart disease is a general term used to describe abnormalities of the
heart or great vessels that are present from birth. Most such disorders arise from
faulty embryogenesis during gestational weeks 3 through 8, when major
cardiovascular structures form and begin to function. The most severe anomalies
are incompatible with intrauterine survival. Congenital heart defects compatible
with embryologic maturation and birth generally affect individual chambers or
discrete regions of the heart, with the remainder of the heart developing relatively
normally. Examples are infants born with a defect in septation (“hole in the heart”),
such as an atrial septal defect (ASD) or a ventricular septal defect (VSD), stenotic
valvular lesions, or with abnormalities in the coronary arteries. Some forms of
congenital heart disease produce clinically important manifestations soon after
birth, which are frequently brought on by the change from fetal to postnatal
circulatory patterns (with reliance on the lungs for oxygenation birth, rather than
the placenta as in intrauterine life). Approximately half of congenital
cardiovascular malformations are diagnosed in the first year of life, but some mild
forms may not become evident until adulthood (e.g., ASD).
A shunt is an abnormal communication between chambers or blood vessels.
Abnormal channels permit the flow of blood down pressure gradients from the left
(systemic) side to the right (pulmonary) side of the circulation or vice versa. When
blood from the right side of the circulation flows directly into the left side (rightto-left shunt), hypoxemia and cyanosis (a dusky blueness of the skin and mucous
membranes) result because of the admixture of poorly oxygenated venous blood
with systemic arterial blood (called cyanotic congenital heart disease). The most
important congenital causes of right-to-left shunts are tetralogy of Fallot,
transposition of the great arteries, persistent truncus arteriosus, tricuspid atresia,
and total anomalous pulmonary venous connection. Moreover, with right-to-left
shunts, emboli arising in peripheral veins can bypass the lungs and directly enter
the systemic circulation (paradoxical embolism); brain infarction and abscess are
potential consequences. Severe, long-standing cyanosis also causes clubbing of the
tips of the fingers and toes (called hypertrophic osteoarthropathy) and
polycythemia.
In contrast, left-to-right shunts (such as ASD, VSD, and patent ductus arteriosus)
increase pulmonary blood flow and are not initially associated with cyanosis.
However, leftto-right shunts raise both flow volumes and pressures in the normally
low-pressure, low-resistance pulmonary circulation, which can lead to right
ventricular hypertrophy and atherosclerosis of the pulmonary vasculature. The
muscular pulmonary arteries (<1 mm diameter) first respond to increased pressure
and flow by undergoing medial hypertrophy and vasoconstriction, which maintains
relatively normal distal pulmonary capillary and venous pressures, and prevents
pulmonary edema. Prolonged pulmonary arterial vasoconstriction, however,
stimulates the proliferation of the vascular wall cells and the consequent
development of irreversible obstructive intimal lesions analogous to the arteriolar
changes seen in systemic hypertension . Eventually, pulmonary vascular resistance
approaches systemic levels, thereby producing a new right-to-left shunt that
introduces unoxygenated blood into the systemic circulation (late cyanotic
congenital heart disease, or Eisenmenger syndrome).
Once irreversible pulmonary hypertension develops, the structural defects of
congenital heart disease are considered irreparable. The secondary pulmonary
vascular changes can eventually lead to the patient's death. This provides the
rationale for early intervention, either surgical or nonsurgical, in those with left-toright shunts.
Some developmental anomalies of the heart (e.g., coarctation of the aorta, aortic
valvular stenosis, and pulmonary valvular stenosis) produce abnormal narrowing
of chambers, valves, or blood vessels and therefore are called obstructive
congenital heart disease. A complete obstruction is called an atresia. In some
disorders (e.g., Tetralogy of Fallot), an obstruction (pulmonary stenosis) and a
shunt (right-to-left through a VSD) are both present.
The altered hemodynamics of congenital heart disease usually cause cardiac
dilation or hypertrophy (or both). However, some defects induce a decrease in the
volume and muscle mass of a cardiac chamber; this is called hypo-plasia if it
occurs before birth and atrophy if it develops postnatally.
LEFT-TO-RIGHT SHUNTS
Atrial Septal Defect
An atrial septal defect (ASD) is an abnormal, fixed opening in the atrial septum
caused by incomplete tissue formation that allows communication of blood
between the left and right atria (not to be confused with patent foramen ovale, see
below). ASDs are usually asymptomatic until adulthood.
Morphology. The three major types of ASDs are classified according to their
location as secundum, primum, and sinus venosus. Secundum ASDs (90% of all
ASDs) result from a deficient or fenestrated oval fossa near the center of the atrial
septum. These are usually not associated with other anomalies, and may be of any
size, be single or multiple, or be fenestrated. Primum anomalies (5% of ASDs)
occur adjacent to the AV valves. Sinus venosus defects (5%) are located near the
entrance of the superior vena cava and may be associated with anomalous
pulmonary venous return to the right atrium.
Patent Foramen Ovale
A patent foramen ovale is a small hole created by an open flap of tissue in the atrial
septum at the oval fossa. In the fetus, the foramen ovale is an important functional
right-to-left shunt that allows oxygen-rich blood from the placenta to bypass the
not yet inflated lungs by traveling directly from the right to left atrium. The hole is
forced shut at birth as a result of increased blood pressure on the left side of the
heart, and the tissue flap closes permanently in approximately 80% of people. In
the remaining 20% of people, the unsealed flap can open when there is more
pressure on the right side of the heart. Thus, sustained pulmonary hypertension or
even transient increases in right-sided pressures, such as occurs during a bowel
movement, coughing, or sneezing, can produce brief periods of right-to-left
shunting, with the possibility of paradoxical embolism.
Ventricular Septal Defect
Incomplete closure of the ventricular septum, allowing free communication of
blood between the left to right ventricles, is the most common form of congenital
cardiac anomaly . Most ventricular septal defects (VSDs) are associated with other
congenital cardiac anomalies such as tetralogy of Fallot; only 20% to 30% are
isolated.
Morphology. VSDs are classified according to their size and location. Most are
about the size of the aortic valve orifice. About 90% involve the region of the
membranous interventricular septum (membranous VSD) . The remainder lie
below the pulmonary valve (infundibular VSD) or within the muscular septum.
Although most VSDs are single, those in the muscular septum may be multiple
(so-called “Swiss-cheese” septum).
Patent Ductus Arteriosus
Patent (also called persistent) ductus arteriosus (PDA) results when the ductus
arteriosus, an essential fetal structure that normally spontaneously closes, remains
open after birth . In the fetal circulation the ductus arteriosus shunts blood from the
pulmonary artery to the aorta, which (like the patent foramen ovale) serves to
bypass the lungs. About 90% of PDAs occur as an isolated anomaly. The
remainder are most often associated with VSD, coarctation of the aorta, or
pulmonary or aortic valve stenosis.
RIGHT-TO-LEFT SHUNTS
The diseases in this group cause cyanosis early in postnatal life (cyanotic
congenital heart disease).
Tetralogy of Fallot
The four cardinal features of the tetralogy of Fallot (TOF) are (1) ventricular
septal defect (VSD), (2) obstruction of the right ventricular outflow tract
(subpulmonary stenosis), (3) an aorta that overrides the VSD, and (4) right
ventricular hypertrophy . All of the features result embryologically from
anterosuperior displacement of the infundibular septum.
Morphology. The heart is often enlarged and may be “boot-shaped” as a result of
marked right ventricular hypertrophy, particularly of the apical region. The VSD is
usually large. The aortic valve forms the superior border of the VSD, thereby
overriding the defect and both ventricular chambers. The obstruction to right
ventricular outflow is most often due to narrowing of the infundibulum
(subpulmonic stenosis) but can be accompanied by pulmonary valvular stenosis.
Sometimes there is complete atresia of the pulmonary valve and variable portions
of the pulmonary arteries, such that blood flow through a patent ductus arteriosus,
dilated bronchial arteries, or both, is necessary for survival. Aortic valve
insufficiency or an ASD may also be present; a right aortic arch is present in about
25% of cases.
OBSTRUCTIVE CONGENITAL ANOMALIES
Coarctation of the Aorta
Coarctation (narrowing, constriction) of the aorta ranks high in frequency among
the common structural anomalies. Males are affected twice as often as females,
although females with Turner syndrome frequently have a coarctatio. Two classic
forms have been described: (1) an “infantile” form with tubular hypoplasia of the
aortic arch proximal to a patent ductus arteriosus that is often symptomatic in early
childhood, and (2) an “adult” form in which there is a discrete ridgelike infolding
of the aorta, just opposite the closed ductus arteriosus (ligamentum arteriosum)
distal to the arch vessels ( Fig. 12-8 ). Encroachment on the aortic lumen is of
variable severity, sometimes leaving only a small channel and at other times
producing only minimal narrowing. Although coarctation of the aorta may occur as
a solitary defect, it is accompanied by a bicuspid aortic valve in 50% of cases and
may also be associated with congenital aortic stenosis, ASD, VSD, mitral
regurgitation, or berry aneurysms of the circle of Willis in the brain.
CONTROL QUESTIONS
1. Diseases of the valve holes of the heart and great arteries: classification, functional
disorders. Congenital and acquired heart disease: clinical and morphological
characteristics.
2. Endocarditis: classification, etiology, pathogenesis, morphological characteristics,
complications, prognosis. Primary endocarditis (bacterial sepsis, endocarditis
Leffler). Non-infectious nonbacterial thrombotic endocarditis. Endocarditis in
rheumatic diseases (true rheumatism, systemic lupus erythematosus, rheumatoid
arthritis). Carcinoid endocarditis.
3. Diseases of the myocardium. Classification. Myocarditis. Definition, etiology.
Patho- and morphogenesis, clinical and morphological characteristics,
consequences, causes of death:
a) primary myocarditis Abramov - Fidler,
b) viral, microbial and parasitic myocarditis, infectious-allergic myocarditis,
c) myocardial diseases caused by toxic, metabolic and other impacts,
d) heart disease in pregnancy and childbirth, amyloidosis, excess iron, hyper- and
hypothyroidism.
4. Diseases of the pericardium. Pericarditis: classification, etiology, pathogenesis,
clinical and morphological characteristics, outcomes. Hydropericardium,
hemopericardium.
5. Cardiomyopathy: classification. Primary cardiomyopathy, the value of genetic
factors, pathological and morphogenesis, clinical and morphological characteristics
of different forms, causes of death. Secondary cardiomyopathy etiology,
pathogenesis, morphological changes of heart complications.
6. Rheumatic diseases. Classification. General characteristics. Rheumatic fever:
etiology, patho- and morphogenesis, the characteristic clinical and morphological
forms, methods of diagnosis, clinical symptoms and syndromes forecast.
7. Congenital heart disease. Etiology. Vices "blue" and "white" types. Congenital
defects of the atrial and ventricular walls, arterial trunks of the heart (transposition,
stenoses and anomalies in the mouths of the great arteries, aortic coarctation,
patent ductus arteriosus), combined heart defects (the triad, tetrad, pentad Fallot).
Clinical and morphological characteristics.
The practical part of the subject:
Slides: In the study micropreparations pay attention to the education elements,
designated by the letters in parentheses.
1. Return warty endocarditis. H & E stain. The valve is thickened, sclerotic and
hyalinized (a), with foci of fibrinoid necrosis, necrosis of the area destroyed by the
endothelium (b) the organized and fresh thrombi (c) in the thickness of the valve the diffuse lymphoid-macrophage infiltration (g).
2. Rheumatoid myocarditis (granulomatous). H & E stain. The stroma of the
myocardium observed tricks fibrinoid necrosis (a) around the necrosis observed
focal perivascular cell infiltrates (Aschoff's body) (b), the Anitschkow cells (c) macrophages, lymphocytes, histiocytes. The fatty degeneration of cardiomyocytes
(g).
3. Fibrinous pericarditis. H & E stain. In epicardial tissue visible fibrin strands (a),
edema and hyperemia of the vessels (B) and macrophage infiltration (c).
macropreparations:
1. Acute warty endocarditis.
Heart enlarged, left ventricular wall thickened, enlarged cavity. On the edge of the
mitral valve are seen small granular thrombotic imposing a "warts", size 1 cm or
more, a dark brown color.
Reasons: infectious-allergic (rheumatic diseases), infectious diseases, intoxication.
Complications thromboembolic syndrome: infarctions of the spleen, kidneys, brain,
bowel gangrene.
Outcomes: valvular heart disease.
2. polypoid - ulcerative endocarditis of the aortic valve.
Hearts increased in size. The walls of the left and right ventricle are thickened,
widened chamber. The flaps of the aortic valve thickened, sclerotic, hyalinized,
deformed and fused. On the edge of the flap and rounded ulceration visible defects.
On the surface of the flap seen massive crumbling thrombotic imposition of polyps
(vegetations). In tendon chords and parietal endocardium organized thrombotic
overlap.
Reasons: bacteremia in severe infections and septicopyemia (drug addicts,
complications intracardiac catheter) is often the background is a previous infectious
diseases and illness, leading to severe changes in heart valves (atherosclerosis,
syphilis, brucellosis, congenital heart disease, patients on hemodialysis,
immunosuppressive therapy ).
Complications: thrombosis, aneurysm wings, perforation, detachment of the valve
and tendon chords. Rarely glomerulonephritis.
Outcomes: heart disease.
3.Fibrosis mitral valve.
Mitral valve thickened, sclerotic, twisted and spliced. Chord shortened and
thickened. Along the edges of the deformed valves are arranged fresh thrombotic
overlay, and organized, which leads to even more wrinkling of the valve leaflets
and insufficient clamping.
Reasons: rheumatism, systemic lupus erythematosus, rheumatoid arthritis.
Complications: thromboembolism.
Outcomes: chronic heart failure, decompensation blemish.
4. Fibrinous pericarditis ("hairy heart"). Heart increased its surface is covered with
rough gray overlays as filaments resembling the scalp. The threads of fibrin are
easily separated.
Reasons: tuberculosis, rheumatic fever, uremia; nonspecific bacterial infection
complicating pyosepticemia (quickly becomes purulent); severe course of viral
infections (influenza, of poliomyelitis, infectious mononucleosis).
Complications: a large accumulation of fluid leads to cardiac tamponade.
Outcomes: absorption of exudate; adhesions, obliteration of the pericardial cavity
with the development of constrictive pericarditis; armored heart.
5. Congenital heart disease (pentad Fallot).
In the heart there is a ventricular septal defect, pulmonary stenosis, right ventricular
hypertrophy, dekstrapozition of aorta (aorta that overrides the VSD) and atrial
septal defect.
Reasons: gene mutations, chromosomal aberrations, exposure to teratogens on the
embryo in the 3-11 th week of fetal development.
Eastern Promises "blue type" (RIGHT-TO-LEFT SHUNTS) blood flow right to
left, followed by a sharp decrease in the volume of blood in the pulmonary
circulation, and severe hypoxia.
The complications and causes of death: right ventricular failure, bacterial
endocarditis, embolic brain abscesses, lung infections.
Outcome: unfavorable.
6. The artificial heart valve.
In the area of the mitral valve is a metal structure provided "flapping" disc enclosed
in a rigid cage, performing the function of the valve.
Causes: congenital and acquired valve.
Complications: infective endocarditis, thromboembolism, dysfunction of the valve.
Test control
Select one or more correct answers
1. cardiomyopathy is characterized
1) valves lesion
2) Coronary thrombosis
3) focal granulomas in the myocardium
4) exudative interstitial inflammation
5) dystrophic cardiomyocytes
2. PRIMARY cardiomyopathy
1) The hypertrophic form
2) Dilated
3) constrictive
4) canalicular
5) The restrictive
3. TITLE rheumatic granuloma
1) focus Abrikosov
2) focus Aschoff Bullet
3) Aschoff's body
4. CELLS IN THE COMPOSITION rheumatic granuloma
1) Lymphocytes
2) macrophages
3) plasma cells
4) foam cells
5) fibrocytes
5. the TRUE NAME RHEUMATISM
1) Lyell's disease (total cutaneous epidermolysis)
2) Buerger's disease (systemic vasculitis)
3) parietal endocarditis with eosinophilia Loeffler
4) All the answers are correct
5) disease Sokolsky-Buyo
6. pathological process of disorganization of connective tissue rheumatism
1) Sclerosis
2) mucoid swelling
3) inflammatory reaction
4) metaplasia
5) fibrinoid changes
7. The primary lesion ORGANS in rheumatism
1) heart and blood vessels
2) the small joints
3) renal pelvis
4) these organs are not affected
8. Inflammatory reactions in rheumatism
1) purulent - exudative
2) predominantly alterative
3) intermediates
4) granulomatous
9. warty endocarditis imposed on in rheumatism CONSTITUTE
1) Aschoff's body
2) granulomas Berezovsky - Sternberg
3) imposition of thrombotic
10. pathogenesis of rheumatic diseases
1) immunodeficiency syndrome
2) violation of transplantation immunity
3) autoimmune reactions
11. MOST PROVEN role in the development RHEUMATISM
1) beta-hemolytic streptococcus group A
2) beta-hemolytic streptococcus group B
3) Herpes Virus
4) kampillobakter
12. The structure of typical rheumatoid granulomas
1) the focus of fibrinoid necrosis
2) focus caseation
3) macrophage cells Anichkova
4) focus liquefactive necrosis
5) reaction neutrophilic
13. SIGNS dilated cardiomyopathy
1) dilatation of the heart chambers
2) dilation of the left ventricle
3) dilation of both atria
4) hypertrophy of the left ventricular wall
5) hypertrophy of the walls of the heart chambers
6) hypertrophy of the right ventricular wall
14. The size of the heart in dilated cardiomyopathy
1) significantly reduced
2) slightly decreased
3) is not changed
4) slightly increased
5) increased significantly
15. CELLS Anichkova in rheumatoid granuloma BE CONSTRUED AS A
1) lymphoid cells
2) plump histiocytes
3) activated plasma cells
4) epithelioid cells
16. EXODUS rheumatic endocarditis
1) brown atrophy of the myocardium
2) the formation of heart disease
3) small-focal cardiosclerosis
4) carcinoid defeat valve
17. RHEUMATIC pancarditis this defeat
1) endocardium and myocardium
2) endocardial and pericardial
3) the myocardium and pericardium
4) endocardium, pericardium and myocardium
18. METAPHORICAL NAME THE HEART AT fibrinous pericarditis
1) "armored"
2) "muscatel"
3) "hairy"
4) "tiger"
5) "sago"
19. endocarditis Libman - Sachs is typical for
1) Rheumatism
2) atherosclerosis
3) Ankylosing spondylitis
4) systemic lupus erythematosus
20. The forms of infectious endocarditis
1) acute
2) subacute
3) chronic
4) undulating
21. Cause of infarction of internal organs in rheumatism
1) aneurysms of large vessels
2) thromboembolic complications
3) beta-hemolytic streptococcus