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Egerton University

Bachelor of Veterinary Medicine and Surgery


Department of Veterinary Pathology, Microbiology and Parasitology
BVM III Feb 2018

VMED321: Systemic Pathology


Female reproductive system

By Dr. Mwihia E.W.


References
• Jubb, Kennedy & Palmer: Pathology of Domestic Animals 1985
3rd, edition Orlando, San Diego, New York etc. 413-556.,
• Thomson’s Special Veterinary Pathology, 3rd edition, Calton,
Magavin, Zachary Eds. Mosby.2000
• James Zachary & M. McGavin. Pathologic Basis of Veterinary
Disease. 6th Edition

Systemic Pathology 2
INTRODUCTION

Systemic Pathology 3
Functions
• produces the ova or oocytes necessary for reproduction
• It is designed to transport the ova to the site of
fertilization.
• Conception, the fertilization of an egg by a sperm,
normally occurs in the fallopian tubes.
• Implantation of fertilized egg into the walls of the uterus,
beginning the initial stages of pregnancy.
• If fertilization and/or implantation doesn't take place,
the system is designed to shed the uterine lining.
• It also produces female sex hormones that maintain the
reproductive cycle.
• Provide nutrients to growing foetus and new born
Systemic Pathology 4
Components

Systemic Pathology 5
Components
• Ovaries – produces eggs and hormones
• Fallopian tubes – where fertilization occurs
• Horns of the uterus – where fetus grows
• Uterus – Provides nourishment for fetus
• Cervix – separates the vagina and uterus
• Vagina – channel for birth and copulation
• Vulva – opening of the reproductive tract
• Mammary glands – provide nutrition for new
born
Systemic Pathology 6
Considerations
• The complex physiologic events that are associated
within the estrus cycle, in pregnancy, or during the post-
partum periods are accompanied by dramatic tissue
changes in the gonads, tubular, and external genitalia,
such as marked hyperplasia, atrophy, necrosis,
hemorrhage, and tissue invasion.
• These are changes that pathologists usually associate
with pathological processes.
• Consequently, when presented with reproductive tissues,
an examining pathologist must start with a firm
understanding of the normal embryology, anatomy, and
reproductive physiology associated with the species
under study.
Systemic Pathology 7
PATHOLOGY

Systemic Pathology 8
Introduction
• Diseases of the female genital system may
interfere with ovulation, fertilization of the egg,
development of the embryo and reproduction.
• Some of these conditions lead to sterility,
premature expulsion of a dead or living fetus
and some may affect offspring.
• The pathogenesis of these diseases involves a
complex interplay of endocrine disturbances,
infectious diseases, non-infectious diseases,
immaturity and senility.
Systemic Pathology 9
1. Generalized developmental anomalies
• During early development of the genital tract, each
individual is bisexual and potentially able to develop
into male or female phenotypic sex.
• The indifferent embryonic gonad develops into an ovary
unless the Y-chromosome (with testis-determining factor)
is present, leading to development of testis.
• The earliest tubular genitalia is also bisexual.
• The Wolffian duct persist and develops if the gonads
are testes whereas if the gonads are ovaries, the
Mullerian duct persists.
• Common generalized developmental anomalies of the
genital system include bovine freemartin,
hermaphrodites and pseudohermaphrodites.
Systemic Pathology 10
Consi
• The

Systemic Pathology 11
1.1 Bovine freemartin
• This is a genetic female bovine calf born as a co-twin with a
male whose genitalia is poorly developed.
• Over 90% of such females have severe hypoplasia of the
genital tract and are sterile.
• The pathogenesis of freemartinism is not fully understood.
• Postulated that since both the male and female co-twin share
a common placental circulation in utero, this allows male
hematopoietic cells to invade and colonize the female twin.
• Also that since the male gonads develop earlier than the
female gonads, androgenic hormones produced by the
testicles of the male fetus may enter the circulation and
suppress the development of the female genitalia.
• The degree of gross modification of the female genitalia
varies.

Systemic Pathology 12
• [G]:The ovary is small, sometimes only represented by a
cord-like thickening on the ovarian ligament.
• The tubular genitalia may vary from cord-like structures to
well-developed uterine horns but communication with the
vagina is always absent
• The vagina and vestibule are hypoplastic and clitoris is
enlarged.
• The mammary glands fails to reach normal size.
• Seminal vesicle and various other male tubular genitalia
may be present.
• [M]: ovarian changes vary from reduced or no germ cells, to
an ovary that contains testicular tissue or partially converted
into a testis.
• The male co-twin usually has minimal effects but may have
low fertility or be sterile.
• Free martinism has also been observed in goats, sheep and
pigs.
Systemic Pathology 13
Bovine (calf) Ovaries, Uterus & Vagina - freemartinism

Systemic Pathology 14
Bovine (twin fetuses) common placenta (Freemartinism)

Systemic Pathology 15
1.2. Hermaphrodites and pseudohermaphrodites

Hermaphrodites
• Also known as intersex
• May be true or pseudo
• True - these have both ovarian and testicular tissue and
can be bilateral or unilateral, can have combined organ
(ovotestis) which has testicular tissue one or both (bilateral)
sides.
• The genital tract cannot easily be classified as male or
female.
• True haemophrodites are rare.
• Pathogenic mechanisms include chimera formation but are
in most cases unknown.
Systemic Pathology 16
• Chimerism - embryonic blood of the twin is exchanged
and leads to permanent colonization by hematopoeitic
cells with the result that each twin acquires tolerance for
the blood cells of the other

Pseudohermaphrodites
• these have chromosomes and gonads of one sex and
tubular organs modified towards those of the other sex.
• are more common.
• further characterized as male pseudohermaphrodite if the
gonadal tissue is male and as female
pseudohermaphrodite if the gonadal tissue is female.
• The male pseudohermaphrodite is more common.
• Pseudohermaphrodites are named according to their
Gonads
Systemic Pathology 17
• True
hermaphrodite
in cattle
– Presence of
vulva and
testicles

Systemic Pathology 18
Systemic Pathology 19
Systemic Pathology 20
1.3 XX sex reversal
• documented in dogs, pigs, goats, and mice.
• Even without a Y chromosome to initiate and sustain male
development, these animals have some kind of recessive
gene on the X chromosome that does the same thing.
• So some testicular tissue develops
• Homozygotes have a testis or ovotestis, and some may
morphologically appear to be males.
• Others are females with an enlarged clitoris and abdominal
testes.
• In dogs, XX sex reversal is most common in American Cocker
spaniels.
• Testicular tissue in these dogs lacks germ cells, and some
dogs with an ovotestis and female tract have been able to
produce litters.

Systemic Pathology 21
1.4 XY sex reversal
• This condition has been reported in horses.
• It is an autosomal dominant inherited condition and may
be a Y chromosome mutation.
• Animals are XY but they generally look like mares.
• The phenotype of affected animals is varied; there may
be phenotypically normal but sterile mares, or individuals
with ovotestes and underdeveloped tracts.

Systemic Pathology 22
1.5 Androgen insensitivity
• This syndrome has been seen in mice, rats, cats, cattle,
horses, and humans.
• A mutation in androgen receptors renders cells insensitive
to testosterone.
• They are genetic males but have more phenotypic
characteristics of females.
• Many humans with this syndrome look very feminine

Systemic Pathology 23
A. Ovaries
Developmental anomalies
1. Ovarian agenesis (no ovaries):
• This condition is most often seen in ruminants, pigs, and dogs.
• Ovarian agenesis can affect one or both ovaries and the
associated tubular genitalia
• may be absent or underdeveloped.
2. Ovarian dysgenesis:
• Small, misshapen ovaries and usually the tubular tract is also a
underdeveloped and weird.
• This condition is seen most often in horses, it is Turner’s
syndrome.
• Animals genetically are XO.
Systemic Pathology 24
3. Ovarian remnants (misplaced bits):
• Sometimes spayed animals still come into heat due to:
– congenitally be small bits of ovary in some location other than the ovary
– incompletely removed ovary snippets might remain and continue to cycle.
4. Hypoplasia of ovaries
• NB: Hypoplastic ovaries are normal in sexually immature animals.
• It may be unilateral or bilateral but the left ovary is more
frequently and severely affected.
• Affected ovaries are small, nonsymmetrical, usually without follicles
and surface scars from previous ovulation and sometimes have
cysts.
• [M]:partial or complete absence of ovarian cortical stroma (germ
cells) and ova.
• In severe bilateral ovarian hypoplasia, there is hyperplasia of
ovaries and tubular genitalia.
Systemic Pathology 25
Bovine Uterus & Ovaries - uterine segmental aplasia

Systemic Pathology 26
Hemorrhage of the ovaries
• Some small haemorrhage occur in ovarian follicle at the
time of ovulation in all species.
• In mares, this may lead to loss of a large amount of blood,
forming a corpus hemarhogicum.
• Haemorrhage may also be extensive in hens.
• Manual expression of persistent corpus luteum as part of
veterinary treatment for sterility sometimes is followed by
severe hemorrhage (blood loss may be several gallons
and result in death of the animal).
• For unknown reasons, intrafollicular hemorrhage occurs in
calves, in follicular cysts of the bitch and occasionally in
atretic follicles of cows.
Systemic Pathology 27
Inflammation of the ovaries
• This is referred to as oophoritis or ovaritis
• It is rare in domestic animals.
• Condition may occur as a result of an ascending infection from
uterus or from the peritoneum.
• Purulent oophoritis is most common and may occur with metritis.
• Necrotizing oophoritis occurs due to infectious bovine
rhinotracheitis virus in post-estrus cow.
• Serosal granulomas on the surface of the ovary may be due to
brucellosis and peritoneal tuberculosis.

Systemic Pathology 28
Cystic ovaries
• Cystic ovaries or cystic ovarian degeneration refers to a condition
in which the ovary contains one or more abnormal cysts.
• occurs in all animals but is most common in cattle, pigs and horses.
• About 16 different types of congenital and acquired cysts may occur
in or around the ovary.
• Acquired cysts may arise from follicles that have not ruptured
(ovulation) or undergo atresia (follicular cysts) and from ruptured
follicles (cystic corpus luteum).
• The causes and pathogenesis of ovarian cysts is complex and
combine the hereditary factors and hormonal disturbances.
• Pathologic cystic ovaries are much larger than normal mature follicle.
• Histological examination and special staining of the wall lining cells
of the cystic structures is essential for appropriate classification.

Systemic Pathology 29
Follicular cysts
• Follicular cysts are common in cattle, pigs and dogs.
• They may occur singly or multiple on one or both ovaries, are
thin walled and usually filled with serous fluid.
• The cysts arise from follicles that fail to ovulate or undergo
atresia.
• [M] the cyst is lined by fat epithelial cells and connective tissue,
the granulose cell layer and ovum are absent.
• The theca is thickened and partially luteinized.
• Follicular cysts undergo spontaneous degeneration.
• Most common example of a follicular cyst is the cystic Graafian
follicle.
• Follicular cysts often cause nymphomania.
Systemic Pathology 30
Cystic Graafian follicle
• This is the most common form of cystic ovarian degeneration.
• The condition is most common in heavy-producing cows and may be
associated with nymphomania due to the estrogenic substances
present in the cyst fluid.
• The condition occurs due to lack of release of pituitary
gonadotrophin in early estrus.
• This leads to no ovulation and luteinization.
• [G] one or more large follicles are present on one or both ovaries.
• There is no corpus lutea in the ovaries, the uterus and vulva are
edematous and flabby, the cervix is enlarged and produces a gray-
white mucus and the clitoris may be enlarged.
• Chronic cysts may lead to the development of uterine hydrometra or
mucometra in cows.
• [M] the ovum is absent and there is degeneration of the granulosa
cells.
Systemic Pathology 31
This is a cystic follicle, so it is called a Follicular cyst. These happen in
multiple species, but most commonly in cattle.
Animals with follicular cysts may have prolonged estrus-like behavior (if they
are producing lots of estrogen), or in many cases they are in anestrus, the
cysts have just caused the ovaries to shut down.
Systemic Pathology 32
Corpus luteum cysts
• Follicle sacs typically dissolve after releasing an egg.
• But if the sac doesn’t dissolve and the opening of the
follicle seals, additional fluid can develop inside the sac,
and this accumulation of fluid causes a corpus luteum cyst.

Systemic Pathology 33
• This is a cystic corpus luteum. Corpus luteum is Latin for "yellow body." It can persist
much longer than it should, and it gets cystic in the middle, then it is abnormal, a
cystic corpus luteum.

Systemic Pathology 34
• Here is another one. These cystic corpora lutea are seen almost exclusively
in cattle. They can get pretty big, and they just continue making
progesterone, which keeps the animal stuck in anestrus. Not much interest in
mating.

Systemic Pathology 35
Atretic follicles:
• During the estrus cycle of uniparous animals, many follicles
develop but only one usually mature and ovulate.
• The remainder undergo atresia, degenerate and
disappear.
• Atresia is a normal process but is pathological when
unnatural influences inhibit the final maturation process.
• Such include in the case of anestrus of malnutrition and in
debility.
• The atretic follicles may become cystic.

Systemic Pathology 36
Results of ovarian cysts
• Pressure atrophy on ovary
• Sterility
• Nymphomania
• Hormonal abnormalities such as the following:-
– 1. Over production of androgens (leading to masculine female),
– 2. Over- production of progesterone and estrogen may have the
following lesions:
• Enlargement and oedema of cervix, uterus, vagina and vulva.
• Endometrial hyperplasia, increased incidences of mammary tumours and
• in prolonged cases, estrogen stimulation results in squamous metaplasia of the
vaginal epithelium.

• In dogs and cats, functional graafian follicular cysts can be


responsible for nymphomania, vulva tumefaction, cystic
endometrial hyperplasia and cystic mammary hyperplasia.
Systemic Pathology 37
Neoplasms of the ovaries:
• Tumours of the ovary are relatively common in all species of
animals but frequently in cattle, dogs, horses and fowls.
• Primary ovarian tumours may arise from the epithelium of the
follicle (epithelial tumours), granulosa and theca cells
(granulosa cell tumours), from primordial germ cells and from
connective tissue.
• Granulosa cell tumours occur in all animals and have the
potential to produce estrogen or androgen.
• Affected animals may exhibit signs of nymphomania and other
effects of high hormonal stimulation.

Systemic Pathology 38
These are teratomas. They form from the primordial germ cells (which are also
puripotential), which are the eggs. They can make fairly bizarre structures - hair,
teeth, bones, liver, kidneys, etc. The good news is that they are almost invariably
Benign. In veterinary medicine we see them most frequently in dogs and cats,
probably because those are the animals we spay, so we happen to see the
ovaries with greater regularity. It is likely that they form with similar frequencies
in many species (including humans) but we just never see them.

Systemic Pathology 39
This is an adenocarcinoma. The cell of origin is the epithelial lining of the
ovary. These tumors seed the abdominal cavity and so are not very amenable
to surgical excision. This tumor is seen most frequently in the dog, although it will
occur in all species.

Systemic Pathology 40
B. Fallopian tubes
• The fallopian tubes (uterine tube, oviduct) is the site of
fertilization and embryo remains there for 3-4 days.
• Primary lesions in the fallopian tubes are rare.

Developmental anomalies
• These are usually associated with malformation of the ovaries
and uterus and include aplasia and agenesis.
• Hypoplasia of oviduct is associated with ovarian aplasia and
atrophy.
• Congenital stenosis of oviduct occurs in some animals.
• Atrophy of oviduct occurs following ovarietomy.

Systemic Pathology 41
Hydrosalpinx
• This is a acquired or congenital condition in which fallopian
tubes are distended with watery serous or mucinous fluid.
• Acquired conditions occur following mechanical or functional
obstruction of the lumen on either end of the tube due to
trauma or inflammation.
• Congenital types usually occur due to segmental aplasia of the
uterine horn. .
• [G]: the distension may be uniform or irregular and the walls
become thin.
• [M]: the condition is characterized by cystic cavities in mucosa
that contain pale pink granular material.

Systemic Pathology 42
Salpingitis
• This refers to inflammation of the oviduct.
• It usually results from spread of infection from uterus and is
usually bilateral.
• [G]: it is often not visible.
• Sometime, there may be some hyperemia, thickening of the
mucosa and small amounts of serous, mucinous, fibrinous or
purulent exudates in the lumen.
• [M]: may vary from mild characterized by only loss of cilia and
desquamation of epithelial cells to severe salpingitis involving
the mucosa to muscle layer with exudates in the lumen.
• There is cellular infiltration into the folds of the mucosa.
• Following severe cases, denuded areas may form adhesions or
be covered with granulation tissue with adjacent mucosa
forming cysts.
Systemic Pathology 43
Purulent Salpingitis
• Purulent salpingitis sometimes accompanied by production of
grossly visible pus in the lumen, a condition referred to
pyosalpinx.
• [G]: grossly visible pus in the lumen
• [M]: there are numerous neutrophils and other inflammatory
cells (lymphocytes and plasma cells) within tissues and mucosal
cysts with scanty epithelium.
• In chronic cases, there is extensive infiltration of all layers of
the tube with mainly lymphocytes and plasma cells.
• The cause is always infectious in cattle, mainly by
streptococous, staphylococcus, mycoplasma and Mycobacterium
tuberculosis.

Systemic Pathology 44
Avian (Emu) Ovary & Oviduct - salpingitis and yolk peritonitis

Systemic Pathology 45
C. Uterus
• The uterus provides a protective environment for the embryo.
• It contains horns, a body and a cervix.
• Histologically, it has an endometrium containing endometrial glands,
myometrium and perimetrium.
• The non-gravid uterus, influenced by estrogen, is relatively resistant
to infection.
• The gravid uterus is influenced by progesterone and is susceptible to
infections.
• Progesterone inhibits endometrial lymphocyte proliferation and
myometrial contractility and predisposes the uterus to infection.
• The cervix, which is only patent during estrus, is an efficient
protective barrier for the uterus.
• Using local antibody production, phagocytes and cytokines, the
normal endometrium is able to mount a local response to invading
pathogens and maintain a sterile environment.
• Endometrial (intraepithelial) lymphocytes, are very important for
defense.
Systemic Pathology 46
Developmental anomalies
• Congenital anomalies are seen in cattle, swine and sheep.
• Agenesis or aplasia of one or both horns is associated with aplasia
of fallopian tubes and anterior vagina.
• Hypoplasia of the entire tubular genitalia is seen in freemartins.
• Hypertrophy of the endometrium and myometrium occurs in response
to excessive or prolonged ovarian hormonal stimulation.
• Atrophy of the endometrium occurs following ovariectomy,
hypopituitarism and chronic wasting disease.
• [G]: the endometrium is flat, thin and grayish.
• [M]: only remnants of endometrial glands remain.
• Adenomyosis is presence of endometrial glands and stroma
between muscle fibers of the myometrium.
• May be congenital or occur following hyperplasia of the
endometrium.
Systemic Pathology 47
Hyperplasia of the endometrium
• Also known as endometrial hyperplasia
• This is excessive proliferation of the endometrium, occurs
in all animals, esp. bitch.
• Causes – excess ovarian hormonal stimulation:
progesterone in dogs, estrogenic in cattle and sheep.
• Occurs in dogs with cystic corpora luteum and cattle with
follicular cysts or granulosa tumours.
• Also in sheep and cattle on pasture legumes of high
estrogens.
• There is hyperplasia of the mucosal epithelial cells and
uterine glands, sometimes resulting in cystic formation.

Systemic Pathology 48
• Condition may be cystic (severe) or non-cystic (mild).
• Non-cystic is usually not recognizable grossly.
• In cystic form, referred to as cystic endometrial
hyperplasia, the endometrium is soft, thick and
spongy.
• Numerous submucosal cysts that appear as milliary to
pea-sized vesicles which contain clear fluid, bulge into
the lumen of the uterus.
• In dog and cat, infection is common and leads to
pyometra.

Systemic Pathology 49
Uterine Displacements/positional changes
• Important are
– inversion,
– prolapse,
– hernia and
– torsion.
• In inversion or invagination, a part of the uterus is
invaginated into the uterine cavity.
• The invaginated part may prolapse into the vagina.
• Uterine prolapse is the appearance of the uterus through
the vaginal.

Systemic Pathology 50
• It is most common in ruminants esp. after parturition and
involving the previously gravid horn.
• The causes of inversion and prolapse are defective
contractions of the uterus after birth, lack of tone,
enlargement of uterus, relaxation of the broad ligament,
prolonged and difficult birth, retained placenta and
postpartum hypocalcemia.
• Uterine herniation either into the thoracic cavity through
the diaphragm or through the inguinal canal (metrocele)
occurs in bitches.
• May be due to trauma.

Systemic Pathology 51
Uterine prolapse happens most commonly in cattle, usually an animal that might be low in
calcium, and maybe had a long parturition. Amazingly, even though the whole uterus
might be hanging out of the cow's vulva, if you can clean it up in time and get it back
inside, the cow is likely to do just fine.

Systemic Pathology 52
Here the uterus is twisted, this is a torsion. This really only happens in pregnant animals,
because there is the extra weight that helps to carry the uterus up and over to create the
torsion. There is then vascular compromise and death of the tissue, which eventually results
in death of the animal.

Systemic Pathology 53
Cow with
prolapsed
vagina and
cervix, on a diet
of moldy corn

Systemic Pathology 54
Inflammation of the uterus
• Is inflammation of the entire uterus – Metritis
• Inflammation limited to the endometrium is endometritis, that
of uterine serosa is perimetritis, and that where the broad
ligament is involved is parameritis.
• These are rarely completely separate from one another.
• Metritis is very common in domestic animals, esp. following
parturition, and often due to infectious agents, mainly bacteria
such as Arcanobacterium pyogenes, streptococci, staphylococcus,
E. coli, Brucella suis, Fusobacterium necrophorus, Klebsiella
genitalium, Salmonella abortivoequina, M. tuberculosis etc.
• Most infections occur following parturition or spread through
coitus (mating) and haematogenous.
• can be non-purulent or purulent and may be acute or chronic.
Systemic Pathology 55
Endometritis
• Inflammatory of the endometrium.
• Almost all uterine infections begin as an endometritis.
• Mostly occurs following parturition.
• In mild forms of endometritis, e.g.. caused by Vibrio fetus
and Trichomonas fetus,
• [G]:gross lesions are absent except slight opacity of
oestral mucus.
• [M]: there is a mild infiltration of inflammatory cells,
particularly plasma cells and lymphocytes in the stroma
and slight desquamation of the epithelium.

Systemic Pathology 56
• In severe form of endometritis, the endometrium is
reddened, swollen, edematous and has a rough surface.
• The uterus is enlarged, flabby and collapsed, the
intercotyledonary areas are eroded and the uterine lumen
contains chocolate-colored lochia. Mucosa has
haemorrhages and intense lymphocytic infiltration.
• In chronic endometritis, the epithelium becomes necrotic
and is replaced by granulation tissue and later fibrous
tissue.
• Uterine glands are depleted.

Systemic Pathology 57
Bovine uterus endometritis

Systemic Pathology 58
Canine uterus chronic suppurative endometritis

Systemic Pathology 59
Bovine uterus multifocal granulomas (Tuberculosis)

Systemic Pathology 60
Metritis
• Involves the entire uterine wall (including the endometrium).
• Occurs common following parturition.
• Septic metritis is a severe and often fatal metritis.
• Metritis is usually due to infections by pus-formers such as
streptococci, staphylococci following parturition.
• [G]: the uterine wall is flaccid, thickened, reddened,
edematous and friable (easily ruptures and result in a
secondary peritonitis).
• There is secretion of fetid uterine exudate via the vagina.
• Serosal surface is granular, congested and with
haemorrhages and fibrin deposits.
Systemic Pathology 61
• [M]: infiltration by mainly neutrophils in acute cases and
lymphocytes in chronic cases, in entire uterine wall.
• Severe metritis may lead to a septicemia and pyeamia.
• Localization of purulent metritis may form an uterine
abscess.

Systemic Pathology 62
Bovine uterus acute metritis

Systemic Pathology 63
Pyometra
• an acute or chronic suppurative infection of the uterus with
an accumulation of pus in the lumen in the presence of a
completely or almost completely closed cervix.
• The uterus is distended and filled with pus
• Common in cow, bitch and cat.
• A mechanical or functional obstruction to uterine discharge
prevents drainage of pus.
• Mechanical obstruction (less often) of the cervix occurs due
to induration and stenosis as a result of prolonged
inflammation particularly endometritis, vaginitis and
cervicitis.
• Functional obstruction (common) of the cervix is influenced
by progesterone from a persistent corpus luteum.
Systemic Pathology 64
• The role of progesterone in the pathogenesis of pyometria
is by:
– increasing the susceptibility of the uterus to infection,
– maintaining functional closure of the cervix
– inhibiting myometrial contractions.
Pyometra in dogs and cats
• Pyometra is severe in dogs and cats.
• Occurs as due to infections which are superimposed on
endometrial hyperplasia.
• The majority of cases occur usually during
pseudopregnancy (in pseudopregnancy, the corpus luteum
is retained and secretes progesterone).

Systemic Pathology 65
• [G] the uterus is markedly enlarged, mucous
membrane is dulls, rough, slightly thickened, with
cysts and covered with necrotic adherent debris .
• The lumen contains a large quantity of turbid
purulent chocolate coloured fluid.
• Streptococcal, E. coli, Proteus and staphylococcal
organisms are commonly isolated.
• Pyometra leds to severe intoxication and
intermittent bacteremia.
• The latter in turn leads to extragenital lesions that
include leukocytosis, selective bone marrow
depression, anemia and severe extramedullary
hematopoiesis.
Systemic Pathology 66
Pyometra in cattle
• Pyometra in cattle is characterized by an
accumulation of pus in the lumen of the uterus
(a few millilitres ounces to several liters) which
is thick and cream or grayish-green in color.
• There is no cervical seal of mucus and a small
amount of pus escapes into the vagina.
• The uterine wall is thick and doughy or it is thin
and fibrosed.
• Pyometria in cattle is usually asymptomatic and
there are no extragenital lesions.
Systemic Pathology 67
Bovine uterus pyometra (C. renale)
Systemic Pathology 68
Neoplasms of the uterus
• Not very common in domestic animals
• Primary neoplasms include:
– Carcinoma in cows
– Leiomyoma in bitch
• Lymphosarcoma in cows is the most common metastatic
neoplasm
• Leiomyomas are multiple and extend to cervix and
vagina
• They are associated with endometrial hyperplasia,
follucular cysts and mammary gland neoplasms
• Oestrogen has a role in producing them
• [G]: leiomyomas are well demarcated but not capsulated,
spherical and vary in size.
Systemic Pathology 69
• Carcinomas are rare in domestic animals but are seen in
cows
• [G}]: firm neoplasms that thicken the uterine wall as they
increase in size
• [M]:pleomorphism, deposition of fibrous tissue
• Metastize to regional LN, lungs and abdominal serosal
surfaces
• Lymphosarcoma in cows – caused by bovine leukaemia
retrovirus
• Affects heart, abomasum, LN and uterus
• [G]: yellow, central areas of necrosis replacing layers of
uterus. Vaginal lesions are multiple, small and Hqic but non-
ulcerated
• [M]:infiltration of neoplastic cells – focal or mutifpcal

Systemic Pathology 70
Spindle-shaped cells, in bundles, very orderly, a tumor found in the wall of the
uterus. This is a tumor of smooth muscle, so it is a Leiomyoma. In humans, these
are called fibroids.
Malignant tumors of smooth muscle are Leiomyosarcomas, they are not nearly
as frequent as the benign variety.

Systemic Pathology 71
gross photo of a leiomyoma projecting out of a dog uterus.
Tumors that get this big are usually benign.

Systemic Pathology 72
Lining cells, that means it is epithelial. From the uterus, invading
into the submucosal tissue, that means it is malignant.
So this is a Uterine adenocarcinoma.
Systemic Pathology 73
D. Cervix
• Cysts – occur in cows and probably all are retention cysts
formed by fusion of the rugae
• Loss of the rugae is first necessary and maybe incidental
to the lacerations of parturition, AI or inflammation
• Are usually small and not significant
• Larger ones may cause partial occlusion of the cervical
canal but of seldom importance
• Stenosis – acquired; consists of fusion across epithelial
surfaces and scarification
• May follow severe laceration or long-standing
inflammation

Systemic Pathology 74
Cervicitis
• Usually an extension of endometritis or vaginitis
• simple cervicitis in cows is seen as [G]: a swelling of the
caudal annular rugae, which are edematous and
hyperemic.
• They soon protrude through the external os into the
vagina, and thin mucopurulent exudate accumulates
between the folds and collects in the vagina.
• [M]: there is epithelial degeneration and desquamation
and infiltration by inflammatory cells that are
predominantly mononuclear.
• Neutrophils penetrate the epithelium and become mixed
with mucus, or in more acute cases there may be flank
suppuration. Systemic Pathology 75
• Cervicitis is not usually more severe than this, although in
older cows the prolapse and tumefaction of the rings may be
grossly obvious.
• Although degrees of prolapse result from inflammation, they
may also predispose to it.
• Slight but progressive degrees of eversion of the cervical
rings occur with succeeding pregnancies to expose portions
of the cervical mucosa to the contaminated environment of
the vagina.
• Chronic cervicitis may lead in time to enlargement and
induration of the cervix with some stenosis, but enlargement
is not a criterion of inflammatory sclerosis.
• Discrete cervical abscesses or suppurative fistulous tracts
occasionally result from accidental injury acquired during
uterine irrigation or artificial insemination.
Systemic Pathology 76
E. Vagina and vulva
• Cysts here are not important in themselves, but they do have
some diagnostic significance.
• They occur as cystic dilations in Gartner's ducts and
Bartholin's glands in cattle.
• They may be isolated or they may have a string-of-beads
disposition, or the whole duct may be present, dilated to I-2
cm and tortuous.
• Abscessation may follow localization of infection in the cysts.
• Ruptures - quite frequently acquired as parturient injuries.
• The mucosa alone may be ruptured, or the whole wall.
• Vulvar atresia or hypoplasia (atresia vulvi) has been
described primarily in camelids.
Systemic Pathology 77
• In extreme cases, the labia are completely fused.
• The condition is believed to be due to an autosomal
recessive gene.
• Rectovaginal constriction is a connective tissue disorder
of Jersey cattle characterized by stenosis of the anus
and/or vestibulovaginal sphincter.
• Bilateral stenosis of the milk veins has also been described
and results in udder edema and ischemic necrosis
• It is a simple autosomal recessive defect.
• Anal stenosis renders transrectal palpation difficult.
• Affected females experience severe dystocia.
• The prevalence of the disease has been substantially
reduced because of identification of carrier bulls.
Systemic Pathology 78
• Tumefaction (swelling) – normal during oestrus
• Excessively large or persistent swelling is abnormal and
may be seen in hyperestrogenism in cases of poisoning in
pigs by mycotoxin zearlenone which also causes mammary
development and tenesmus that leads to rectal prolapse.
• Inflammation: vaginitis and vulvitis
• The vagina and vulva are lined by stratified squamous
epithelium which is quite resistant to infections.
• Post parturient vulvitis and vaginitis occurs when they are
lacerated during dystocia and become infected.
• Granular vulvitis in cows maybe associated with
Mycoplasma
• Infectious pustular vulvovaginitis of cattle is caused by
bovine herpes virus I
Systemic Pathology 79
• Neoplasms – transmissible venereal tumour (TVT) of dogs
is viral and transmitted by coitus.
• [G]:begins as a nodule under genital mucosa proliferating
into lumen of vagina and can protrude through the vulva
as an ulcerated mass.
• [M]:the neoplastic cells are large, round or oval and
uniform in size. Cytoplasm is poorly defined and stains
lightly. The number of cells in mitosis is increased.
Spontaneous regression of the neoplasm occurs and
neoplasms have multifocal necrosis, infiltration of
lymphocytes and deposition of collagen.
• May metastase to other sites
• Squamous cell carcinoma – occurs in mature cows, ewes
and mares.
Systemic Pathology 80
• Solar radiation is the cause
• Originates on the hairless and less pigmented skin of the
vulva
• The appearance and behavior is similar to squamous cell
carcinomas in other sites
• Metastases late in the course of the disease to the iliac
lymph nodes

Systemic Pathology 81
These are epithelial cells, they are connected together, and they
are making squames (arrow). They are invading into the wall, so
it is malignant.
Therefore, this is a Squamous cell carcinoma.
It can happen in the vagina and vulva, because these areas are
lined by squamous cells.
Systemic Pathology 82
F. Pathology of pregnancy
• The placenta and fetus are susceptible a number of
pathological conditions.
• Extrauterine pregnancy or ectopic pregnancy, is the
development of embryo outside the uterine cavity as a
result of implantation of the ovum or displacement of the
foetus.
• The fertilized ovum may be implanted in the ovary
(ovarian pregnancy) in the bursa ovarica (bursal
pregnancy) in the fallopian tube (tubular pregnancy) or in
the abdominal cavity (abdominal pregnancy).
• Ectopic pregnancy is very rare in animals.

Systemic Pathology 83
Dropsy of foetal membranes & foetus
• This is the excessive accumulation of foetal fluids and oedema
of the foetal membranes
• The lesions are rare, occur mostly in bovine.
• Hydramnios and hydroallantois refer to an accumulation of
fetal fluid in the amniotic and allantoic cavities, respectively.
• The two often occur together and there is usually oedema of
the foetus (anasarca)
• Normally, about 6 to 15 liters of allantoic fluid and 3 to 6
liters of amniotic fluid occur in the cow.
• The causes are unknown but thought to be obstructive in nature
and is associated with foetal malformations and abnormal
(adventitial) placentation.
• Important sequelae are dystocia, uterine paresis, placental
retention, acute metritis and abortion.
Systemic Pathology 84
• Hydroallantois

Systemic Pathology 85
Other conditions
• Endometrial fibrosis – seen in mares as a result of previous
endometritis.
• It reduces the area of the endometrium available for formation
of a diffuse placenta.
• Chorionic villi do not develop where there is no endometrium.
• Severely affected mares become pregnant but do not carry
the foetus to term because the functional area of the placenta
is toto small.
• Premature placental separation: seen in mares
• Two forms. 1. occurs around parturition time and 2. occurs
before parturition
• Prematurely detached areas become brown and dehydrated

Systemic Pathology 86
• Torsion of the umbilical cord: causes abortion in mares
• The cord is long, excessively twisted and difficult to undo
• [G]: cord is oedematous and haemorrhagic and congested
• Lesser degrees of torsion occurs without seriously affecting
the umbilical blood vessels and killing the foetus
• Placental mineralization
• Mineralization—milky appearance, not gritty if normal.
cf. dystrophic mineralization
• Adenomatous dysplasia, equine
• Nodules (usually 1-5 cm) on allantois near umbilical stalk
• Usually associated with fetal disease, but cause-effect
relationship not known
• Adventitial placentation (ruminants)
• Small to large irregular placentome-like structures may
develop on the placenta adjacent to normal placentomes.

Systemic Pathology 87
Placental
mineralization,
equine

Adventitial
placentation,
bovine

Systemic Pathology 88
• Amniotic plaques
• Foci of squamous
epithelialization,
concentrated around
umbilical stump—no
consequence

Systemic Pathology 89
Systemic Pathology 90
Prolonged gestation
• Fescue toxicosis
– Common in mare grazing endophyte-infected
fescue
– Placenta is thickened and heavier than normal
– Abortion can occur
• Veratrum californicum—ewes
– Associated with cyclopian deformities
• Genetic forms—dairy breed cows

Systemic Pathology 91
Fetal death
• The foetus in the uterus may die at any stage of the
development due to non-infectious or infectious causes.
• Death of microscopic conceptus (embryo death) and
macroscopic conceptus (fetal death).
• In uniparous, the dead fetus may be expelled or retained.
• In early pregnancy, when the main source of progesterone
is the maternal ovary, death of the fetus results in
resorption, maceration or mummification.
• In later gestation, when progesterone is from the fetal-
placental unit, fetal death is usually followed by expulsion
of the fetus.

Systemic Pathology 92
• In multiparous species, one or several dead fetuses may
be retained with the viable ones and delivered at
parturition.
• If most of the fetuses die at the same time, all are likely to
be aborted (live and dead fetuses).
• A dead fetus may be aborted, mummified or macerated.
• Abortion is the expulsion of a dead fetus prior to the time
of expected viability, whereas stillbirth is the expulsion of
a dead foetus after a full normal gestation period.

Systemic Pathology 93
Fetal mummification
• A mummification is a process in which a fetus dies and in
the absence of infection and putrefaction, undergoes
subsequent autolysis with sterile liquification of soft tissues
and reabsorption of fluids.
• These fluids are reabsorbed via the maternal blood and
lymphatics.
• Eventually, the entire fetus becomes brown or black and
leather-like mass with no exudate or odor.
• A completely mummified fetus consists of dried wrinkled
skin and bones.

Systemic Pathology 94
• The time required for complete mummification will depend
on the size of the fetus and is about 6 to 8 months for a 6-
month-old bovine fetus.
• This condition occurs most commonly in multiparous species.
In uniparous species, the mummified fetus may be retained
indefinitely.

Systemic Pathology 95
Systemic Pathology 96
Maceration and emphysema of fetus:
• Fetal maceration refers to a process in which a dead,
retained fetus undergoes autolysis in the presence of a
uterine infection usually by bacterial organisms.
• The usual causes of fetal death and maceration are not
potent gas producers.
• If the cervix is open and putrefactive organisms invade the
uterus and dead fetus, there is excessive gas formation
resulting is fetal emphysema.
• Fetal bones resist maceration and remain in the uterus that
usually has endometritis of pyometra.

Systemic Pathology 97
Maceration

Systemic Pathology 98
Systemic Pathology 99
Placentitis:
• Inflammation of the placenta
• Seen in horses
• May be due to an infectious agent: bacteria, viruses, fungi
etc
• May arise as an ascending infection; haemotogenous
infection or an unknown infection
• Can lead to abortions

Systemic Pathology 100


Placentitis in Brucellosis

Systemic Pathology 101


Equine
streptococcal
placentitis

Systemic Pathology 102


Mycotic abortion,
placentitis

Systemic Pathology 103


Caprine toxoplasmosis, placentitis

Systemic Pathology 104


photomicrograph of one of these
cotyledonary areas of necrosis,
each of the purple blobs is a
Toxoplasma cyst and associated
necrosis.
Toxoplasma can cause multifocal
necrosis of cotyledons. Each of the white
dots in the cotyledons is a focus of
necrosis. Lesions are primarily in the
placenta.

Systemic Pathology 105


acute severe, extensive fibrinous placentitis

Systemic Pathology 106


Infectious causes of abortion
• The pathological changes in uterus, placenta, foetal
membrane and foetus are commonly caused by specific
infectious agents.
• These agents include bacteria, Chlamydia, fungi and
viruses.
• Important ones include Brucella spp, Trichomonas foetus,
Vibro fetus, chlamydia spp, Salmonella spp. Listeria spp.,
equine herpesvirus, fungal organisms and others.

Systemic Pathology 107


This is a mycotic abortion. Regular fungus gets into the
systemic circulation, stops off at the uterus, and grows there,
creating serious inflammation. Calf dies because placenta is
its lifeline.

Systemic Pathology 108


G. Mammary gland
• Function is production of milk for offspring and man.

Development anomalies
– Polythelia
• is a condition where there are accessory teats.
• This may occur alone or together with an increase in the
number of mammary glands or polymastia.
• Lack of a central duct and external teat orifice sometimes
occurs.
• Acquired fistula may also be produced by trauma, abscess
and necrosing inflammation.
Systemic Pathology 109
– Gynaecomastia
• is hypertrophy of mammary gland in the male.
• The glands may secrete a serous fluid or milk.
• Condition seen in man, cattle, goats, sheep, deer and dog
and affects normal animals and those with abnormalities
such as crytorchidism, hypoplasia of testes etc.

– Melonosis:
• Occurs in pigs. Melanin is scattered along the gland ducts.

Systemic Pathology 110


Circulatory disturbances
• Hyperemia of the udder occurs physiologically shortly
before or after parturition.
• Pathological hyperemia occurs due inflammation.
• The capillaries round the acini may be greatly dilated and
filled with blood.
• Oedema - Physiological oedema of the mammary glands
occurs shortly before or after parturition.
• Pathological oedema may be due to hormonal dysfunction
or due to inflammation.
• Haemorrhages occur due to mastitis or trauma.

Systemic Pathology 111


• Embolism, thrombosis and infarction are frequent in
cows and may affect the whole quarter.
• Infarcted areas becomes marked off by inflammatory
zone and may become encapsulated, undergo
abscessation or slough off.

Systemic Pathology 112


Mastitis
• Is inflammation of the mammary glands.
• It occur in all domestic animals and is caused mostly by
infectious agents and very rarely by mechanic injury or
toxic agents.

Mastitis in bovine and related animals


• The causes of bovine mastitis are more than 50 species of
bacteria and more than 20 species of fungi.
• Poor milking hygiene, faulty milking machines and trauma
are predisposing factors.

Systemic Pathology 113


• The bacterial pathogens most commonly recovered from
mastitis are Staphylococcus aureus, Streptococcus
agalactiae, other streptococci, coliform organisms,
Corynebacterium pyogenes and Pseudomonas aeruginosa.
• Some of the bacteria are normal inhabitants of the
mammary gland e.g.. Streptococcus agalactiae, while the
majority enter the udder from outside.
• The normal inhabitants cause mastitis following reduction
of the animal’s resistance or enhancement of bacterial
virulence.
• Infection of the udder may occur through the teat canal
(usual route) or by blood stream.

Systemic Pathology 114


Classification of mastitis
• Mastitis can be classified depending on the:
– morphological appearance,
– time duration (as acute and chronic mastitis) and
– depending on the etiological agent.

Acute catarrhal mastitis


• Characterized by a mild systemic response of short
duration. Individual quarters are affected.
• Secretions may be bloodstained and contain flakes of pus.
• [G]: affected lobules are pale, firm and project above the
cut surface.
Systemic Pathology 115
• Flakes of purulent exudate are present in the cisterns and
lactiferous ducts.
• Edema may be mild or pronounced.
• [M]: the alveoli within lobules are filled with neutrophils.

Chronic catarrhal mastitis


• This follows the acute form.
• [G]: the affected quarters appear smaller than normal,
and are tough or hard in consistency due to glandular
atrophy and fibrosis

Systemic Pathology 116


Acute haemorrhagic mastitis
• also necrotizing or gangrenous
• It produces severe swelling of the affected quarter and a
systemic reaction, which is often fatal.
• This type of mastitis is caused by haemolytic staphylococci,
E.coli and C. pyogenes, B. cereus.
• [G]: the tissue is intensely hyperemic and hemorrhagic with
areas of necrosis.
• Necrotic areas are dirty-brown discolorations surrounded
by haemorrhages.
• The exudates in the ducts and cisterns is often scanty, but
sero- sanguineous or fibrinous.

Systemic Pathology 117


• If the animal survives, the necrotic areas become
sequestrated and eventually slough off.
• There is acute lymphadenitis of udder lymph nodes.
• [M]: there is loss of normal tissue architecture and
embolism, thrombosis and infarction of udder vessels and
lymphatics.

Systemic Pathology 118


Suppurative mastitis
• Caused by Actinomyces pyogenes, Pseudomonas aeroginosa.
• Consists of multiple abscesses with yellowish green pus of a
foul odour, which may discharge through the skin.
• [M]: there is suppurative inflammation in milk ducts, acini
and interstitial tissue that is characterized by intense
leucocytic infiltration and ductal wall destruction.
• Some of these cells also accumulate in the lumens.
• In chronic cases, there is also connective tissue proliferation
in tissues bordering the inflamed areas.

Systemic Pathology 119


Granulomatous mastitis
• This is characterized by a chronic granulomatous
inflammation.
• Caused species of Mycobacterium, Nocardia, Cryptococcus,
etc.).

Systemic Pathology 120


Streptococcal mastitis:
• Bovine mastitis caused by Streptococcus agalactiae mastitis
is one of the more important forms of mastitis in the
bovine.
• The organisms’ sole natural habitat is the mammary tissue
of the cow and goat.
• [G]: more than one quarter is affected and most severe
changes are in the distal portion of the gland around the
cisterns and larger ducts.
• The glandular tissue is grayish, swollen, turgid and with
distinct lobulations on cut surfaces.
• There is systemic reaction and inflammation of regional
lymph nodes.
Systemic Pathology 121
• [M]: in acute stage there is severe edema and an
extensive infiltration of neutrophils into interlobular tissue
and acini and vacuolation and desquamation acinar
epithelial cells.
• In chronic stages, cisterns and ducts are heavily infiltrated
with macrophages and plasma cells and there is fibrosis in
surrounding tissues.

Systemic Pathology 122


Bovine fibrinous mastitis, Streptococcus

Systemic Pathology 123


Staphylococcal mastitis
• Staphylococcus aureus is the most important cause of
mastitis in most dairy animals.
• The organism is ubiquitous and can colonize the skin as
well as the udder.
• Staphylococcus aureus can cause peracute, acute,
subacute, chronic, gangrenous and subclinical types of
mastitis.
• Peracute and acute mastitis usually occurs shortly after
parturition, produces gangrene of the affected quarters
and has a high mortality.

Systemic Pathology 124


• [G]: the affected tissues are swollen, tense, hot, firm and
painful.
• Milk secretion is reduced.
• Gangrenous tissues become blue and eventually black in
color.
• The acute non-gangrenous forms is characterized necrosis
and intense leucocytic infiltration in surrounding tissues.
• A granulomatous mastitis may result.

Systemic Pathology 125


Bovine gangrenous
mastitis,
S. aureus

Systemic Pathology 126


Coliform mastitis
• Most commonly caused by E.coli, Klebsiella spp.,
Enterobacter (Aerobacter) spp. and Citrobacter freundii.
• These organisms may produce mild acute or peracute
forms of mastitis around calving period.
• The infection is usually limited to one quarter and is of a
short course.
• The coliform organisms multiply very rapidly, produce a
large amount of endotoxin, which in turn causes mastitis
and systemic reaction.
• [G]: there is a haemorragic and necrotizing mastitis.

Systemic Pathology 127


Actinomyces pyogenes mastitis:
• Actinomyces pyogenes may cause mastitis in lactating,
non-lactating and immature udders.
• Organism commonly causes suppurative mastitis in cattle
and swine.
• Multiple abscesses with foul greenish-yellow, thick or thin
pus are formed in milk ducts and fistulas may form at the
base of the teat.
• In some cases, necrosis and sloughing off tissue.

Systemic Pathology 128


Mastitis due to Pseudomonas
• Mastitis due to Pseudomonas aeroginosa is rare.
• Mastitis caused may be mild, acute, peracute or chronic
and is generally characterized by suppuration and
abscess formation.

Systemic Pathology 129


Crytococcal mastitis
• Caused by Cryptococcus neoformans and usually affects
more than one quarter.
• In the acute stage, there is severe swelling and increased
firmness of the gland and subcutaneous oedema.
• On cut surface, the affected tissues appear grayish-white
with foci of haemorrhages and are very slimy with thick
slimy grayish secretion.
• In chronic cases, affected tissue becomes involuted and
contains numerous granulomas.
• [M]: the epithelial cells of the acini become detached from
the basement membrane and undergo lysis.
• The acini and ducts contain large numbers of the fungal
organism and are infiltration by foamy macrophages
which also contain the fungal organisms.

Systemic Pathology 130
Mastitis in other species
• Ovine progressive pneumonia virus causes mastitis in
sheep,
• characterized by diffuse interstitial accumulation of
lymphocytes and focal degeneration of ductal epithelium
but no clinical and gross lesions.

Mycoplasma agalactiae
• causes mastitis in ewes and does.
• The disease is characterized by oedema of interstitium in
mammary glands and other lesions in joints and eyes.

Systemic Pathology 131


• Pasteurella haemolytica causes mastitis in lactating ewes,
sometimes associated with rhinitis and pneumonia in their
lambs.
• One or two quarters are involved: swollen, watery
secretion, followed by necrosis, abscessation and even
slough off.

• Mastitis in not common in dogs and cats.


• Occurs as sequela to minor lesions on nipples, with
mammary hyperplasia or neoplasia.
• Usually caused by streptococci, staphylococcus and is
suppurative and necrotizing.

Systemic Pathology 132


Neoplasms of the mammary gland:
• Mammary neoplasms occur frequently and are often
fatal in the dog and are seldom observed in other
domestic species.
• In the dog, mammary tumors may consist of epithelial
and/or connective tissue components.
• Mammary tumors represent approximately 25% of all
neoplasms in female dogs, about 50% of these tumors are
benign mixed mammary tumors and about 25% are
adenocarcinomas.
• The remainder are adenomas, duct papillomas,
myoepitheliomas and malignant mixed mammary tumors.

Systemic Pathology 133
Canine benign mammary neoplasia

Systemic Pathology 134


Canine mammary neoplasia, malignant

Systemic Pathology 135


• Other common lesions of the udder include
– traumatic lesions,
– Vesicles due to Foot and Mouth Disease,
– Pseudocow pox and
– parasites such as ticks, fleas, besnoitia, etc.

Systemic Pathology 136


Bovine skin of teats ulceration, proliferative nodules (Cow Pox)

Systemic Pathology 137


Bovine skin of udder (Pseudocow Pox)

Systemic Pathology 138


Bovine teat vesicles (Foot and Mouth disease)

Systemic Pathology 139


Bovine skin of teats ulceration, proliferative nodules (Cow Pox)

Systemic Pathology 140


Systemic Pathology 141

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