Systemic Pathology Lecturer- Female Genital System - Dr. Saevan S. Al-Mahmood
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Ministry of Higher Education and Scientific Research (MHESR)
University of Mosul (UM)
College of Veterinary Medicine (CVM)
Department of Pathology and Poultry Diseases (DPPD)
Systemic Pathology
of Female Genital
System
By
Lecturer
Dr.
Saevan S. Al-Mahmood
For Undergraduate Students
Systemic Veterinary Pathology
2016 – 2017
Systemic Pathology Lecturer- Female Genital System - Dr. Saevan S. Al-Mahmood
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I- Abnormalities of Phenotypic Sex
1-Female pseudohermaphrodites
May result from iatrogenic administration of androgens or
progestagens to their pregnant mothers.
2- Male pseudohermaphrodites
May result from;
(a)
Androgen insensitivity, caused by a deficiency of
intracellular androgen receptors, MIS is still produced by Sertoli cells in
the testes, and therefore paramesonephric duct derivatives are absent,
animals have normal-appearing female external genitalia, the gonads are
clearly testicular, but present in the normal ovarian position.
(b)
Failure of
regression of paramesonephric ducts (e.g. Miniature Schnauzer), possibly
from failure of production of MIS by Sertoli cells.
II- Abnormalities of Ovaries
1- Follicular cysts or cystic graafian follicles
Result from failure of mature follicles to ovulate. Follicles larger
than they should normally be at ovulation (>2.5 cm in cattle), persistence
(≥10 days in cattle), and possible associated signs of hyperestrogenism
are features of cystic follicular disease. (Diameters of normal follicles
near ovulation are approximately 2 cm in the cow, 1 cm in the sheep and
pig, and 0.75 cm in the dog.)
Follicular cysts may be single or multiple. They are best recognized
in dairy cows but are also common in sows in which they are an
important cause of infertility. They probably result from an aberration
(either absence or mistiming) of the pre-ovulatory surge of luteinizing
hormone from the pituitary gland. Possible causes of this aberration are:
ovarian cycles occurring before the first postpartum ovulation, association
with intrauterine infection, withholding of the animal from breeding for a
prolonged period of time, and genetic predisposition.
Follicular cysts can cause prolonged estrus cycle or anestrus. When
they persist, they can cause changes related to prolonged estrogen
stimulation, e.g. nymphomania, enlarged uterus with edematous wall,
cystic endometrial hyperplasia, enlarged cervix, edema of vulva, enlarged
clitoris, cystic Gartner's ducts (mesonephric duct remnants that lie in the
wall of the vagina), and cystic Bartholin's glands. Polycystic ovarian
disease in the bitch is rare but can result in hyperestrogenism which may
cause bone marrow suppression leading to pancytopenia, sometimes
lethal.
Microscopically
1-Degeneration of granulosa cells, the cell undergo pyknosis,
karyohexis and sloughing in the lumen of cyst.
2- The oocycte undergo degeneration.
Systemic Pathology Lecturer- Female Genital System - Dr. Saevan S. Al-Mahmood
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3- Changes in tunica interna is variable it may be luteinized in some
cases and degenerated in other and infiltrated by fibrous tissue.
2- Luteinized (or lutenal) cysts
Develop when ovulation fails to occur and the granulosa cells and
theca interna cells undergo luteinization. They are a milder form of
follicular cysts and are more common. They may cause prolonged
anestrus due to elevated progesterone. Multiple luteinized cysts are a
distinctive feature of cystic ovarian disease in swine, the endometrium
shows hyperplasia of progestational type, and the clitoris is enlarged.
A luteinized cyst must be distinguished from a cystic corpus luteum,
which has formed after ovulation. The latter is not evidence of ovarian
malfunction and does not interfere with the estrus cycle. In contrast to a
luteinized cyst, a cystic corpus luteum has an ovulation papilla that
distorts the outline of the cyst at the point of ovulation.
III- Abnormalities of Uterine (Fallopian) Tubes
1- Hydrosalpinx
May be congenital, secondary to segmental aplasia of the uterus, or
secondary to trauma (e.g during manual manipulation of the ovary in
cattle) or chronic inflammation. It is a common cause of sterility in sows.
2- Salpingitis
Is usually secondary to endometritis and may lead to pyosalpinx
(salpinx = tube). Even minor inflammatory changes in the uterine tube are
important because of the delicate functions of its ciliated epithelial lining
(propulsion of the ovum, dissolution of the cumulus oophorus [aggregate
of granulosa cells containing the oocyte] prior to fertilization, and
maintenance of a luminal environment suitable to the survival of the
ovum). The salpingeal mucosa has much less capacity for repair than
does the endometrium.
IV- Abnormalities of Uterus
1- Non-inflammatory diseases
A-Rupture:
can be from trauma at parturition or iatrogenic during
infusion or obstetrical manipulation. It can lead to fatal internal
hemorrhage or perimetritis and peritonitis.
B-Torsion:
occurs in a uterus enlarged by pregnancy, pyometra or
mucometra. Rotation tends to occur at the level of the cervix in the
cow and at the junction of the uterine horn and body in the bitch and
queen. It is uncommon except in the cow and the mare, accounting for
5- 10% of serious cases of dystocia in mares. Minor degrees of
Systemic Pathology Lecturer- Female Genital System - Dr. Saevan S. Al-Mahmood
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torsion (up to 90%) are fairly common in cows and apparently resolve
themselves. Torsions of 180 or more cause dystocia and interfere with
circulation. If the fetus dies and air and bacteria enter the uterus, the
fetus putrefies. If the cervix remains closed, the fetus mummifies, if
the uterus ruptures, the fetus escapes into the abdominal cavity but
still undergoes mummification. In some cases, the mummified fetuses
can remain in the peritoneal cavity for months or years without
causing clinical signs.
C-Endometrial hyperplasia:
is usually due to excess hormonal
stimulation. In farm animals, it occurs during prolonged
hyperestrogenism as seen in cystic ovarian disease, granulosa cell
tumors, or following ingestion of estrogenic pastures (such as some
strains of clover) or of grain contaminated by the mycotoxin
zearalenone. Lesions are at first simple, then cystic, and can become
infected, leading to pyometra. The cystic lesions are probably not
reversible. In the bitch, a low-grade, subclinical bacterial infection of
the uterus may cause the endometrium to proliferate during the luteal
phase of the estrous cycle, when it would normally be responsive to
the presence of embryos in the pregnant animal and become an
intimate part of placental structures. This demonstrates the sensitivity
of the canine endometrium to intraluminal material during this phase
of the estrous cycle. Changes in the uterine environment may then
lead to massive bacterial proliferation, transforming the subclinical
infection into pyometra. Endometrial hyperplasia is a significant
precancerous lesion in women, but not in domestic animals.
D-Adenomyosis:
is the presence of nests of endometrial glands within the
myometrium, either as a malformation or by hyperplastic overgrowth
of the endometrium (as in cystic endometrial hyperplasia). By
comparison, endometriosis in women describes the presence of
endometrial glands outside the uterus, including the ovaries, pelvic
peritoneum, and other locations. Its pathogenesis remains unclear.
Suggested causes include:
1)
back flow of menstrual tissue through the
uterine tubes and subsequent implantation, and
2)
metaplasia of the
peritoneal epithelium into endometrial tissue, in both instances, the
process could be aided by vascular or lymphatic dissemination. This
condition can cause a number of problems, including infertility and
pelvic pain.
Systemic Pathology Lecturer- Female Genital System - Dr. Saevan S. Al-Mahmood
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2- Inflammatory Diseases
Uterine infections are mostly ascending through the cervix, less
commonly hematogenous, occasionally from the ovary and uterine tube,
and rarely transneural as in herpesvirus infection.
The non-pregnant uterus is highly resistant to infection.
Defence
mechanisms are both innate and adaptive.
(A)
The innate defences
are
much more important but are not fully understood. They include, as
examples: uterine motility (increased during estrus), migration of
neutrophils into the uterus (more active under the influence of estrogen
during estrus), and mechanical barrier provided by the cervix.
(B)
Adaptive
defences
include humoral and cellular immunity, but these are carefully
controlled in order to tolerate spermatozoa and fetus. Resistance is greatly
reduced under the influence of progesterone during the luteal phase of the
estrous cycle and during pregnancy. Much of this reduced uterine
resistance is related to the secretion into the uterine lumen of
progesterone-induced immunosuppressants that are capable of inhibiting
lymphocyte proliferation. Resistance is also low after birth, especially if
there has been dystocia or traumatic laceration of the genital canal or if
there is retained placenta or slow uterine involution - all conditions that
cause or are related to uterine atony (
chronic Inflammation
).
A- Endometritis
refers to inflammation of the endometrium. At necropsy,
acute endometritis is difficult to diagnose grossly unless there is
copious fibrinous, purulent or necrotic exudate. One should always
consider the stage of estrous cycle or the interval postpartum before
making a gross diagnosis of endometritis. In cattle, a few leukocytes
in the endometrial stroma are present during the estrus and follow
within 2-3 days of parturition. In the mare, however, the presence of
neutrophils in the endometrial stroma is abnormal. Chronic
endometritis is characterized by an accumulation of plasma cells and
lymphocytes in the endometrial stroma and by periglandularfibrosis.
Endometrial biopsy in mares is used as a breeding management
tool because the severity of endometritis is correlated directly with the
inability of the uterus to maintain pregnancy. In cattle, endometritis
may result from dystocia and retained placenta in the early
postpartum period, or at various times after breeding as a result of
venereal infection (e.g. Tritrichomonas fetus) with early embryonic
death. Inhibition of the synthesis and release of the luteolytic factor
prostaglanding F2α by the chronically diseased endometrium causes
retention of the corpus luteum. Progesterone secreted by this retained
corpus luteum increases the susceptibility of the uterus to infection,
maintains functional closure of the cervix, and inhibits myometrial
contractility, all factors that can eventually lead to pyometra.
Systemic Pathology Lecturer- Female Genital System - Dr. Saevan S. Al-Mahmood
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B- Metritis
is inflammation of all layers of the uterine wall. The uterus is
paretic and there may be little or no vaginal discharge.
C- Pyometra
is accumulation of pus in the lumen of the uterus. Escape of
the pus is usually prevented by a functionally closed cervix. Pyometra
in the bitch is a disease that characteristically affects older animals,
especially those that are not bred. The condition most often develops
a few weeks after estrus. The cervix is closed as a functional response
to luteal hormones. The uterine wall is friable, and rupture or
perforation with secondary peritonitis may occur. Microscopically,
there is remarkable endometrial hyperplasia. The bacteria most
commonly present in pyometra are strains of E. coli that are also
present in the feces, most of these strains are also urinary tract
pathogens, and their uropathogenic virulence factors may enhance
their pathogenicity in the genital tract. Pyometra can be a life-
threatening condition in the bitch. There can be severe bacterial
toxemia, bone marrow depression, glomerulonephritis resulting from
immune-complex deposition, and polyuria from impaired renal
tubular ability to concentrate urine, which may also have an
immunologicbasis.
In cattle, pyometra is not usually life-threatening as it is in
bitches. In mares, hormonal influences associated with pyometra are
much less important than they are in other species like the cow and
the bitch. The cervix is not closed, and copious amounts of pus can be
discharged. However, the gravitational pull of the flaccid, distended
uterus over the brim of the pelvis may limit the discharge of pus.
Pyometra in the mare rarely leads to evidence of systemic disease,
although some mares develop a mild anemia.
V- Abnormalities of Placenta and Fetus
1- Infectious causes of abortion
A- Viral infection:
Herpesviruses in several species can cause fetal lesions characterized by
multifocal necrosis in a wide variety of organs. Often, there are no gross
placental lesions.
B- Bacterial infections
1- Brucellosis
There is much similarity in the diseases produced in the different
hosts by the various strains of Brucella. Infections by any of these
organisms are initially systemic, and relapsing bacteremic phases are
common in the persistent infections. Localization and persistence of
infection may occur in many organs. Some organs, however, notably the
Systemic Pathology Lecturer- Female Genital System - Dr. Saevan S. Al-Mahmood
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genitalia and placenta, are noted for the regularity with which they
develop intense persistent foci of infection. Most Brucella spp. are
potential zoonoses.
* Brucella abortus in cattle
(Pathogenesis of Infection)
Infection by Brucella abortus is mainly
through ingestion of feed contaminated with products of abortion. Once
infection is established in sexually mature animals, females especially, it
tends to persist indefinitely. Young cattle are relatively resistant up to
about the age of puberty, they normally throw off the infection in the
course of a few months, without significant effects. In older animals,
regional lymphadenitis is followed by bacteremic waves and early
localization in various organs, particularly the spleen and mammary gland
and lymph nodes in females and the lymphoid tissues, testis and
accessory glands in males, synovial structures may also be involved, with
resulting purulent tendovaginitis, arthritis, or bursitis. (Ingestion of
contaminated milk is an important source of infection for children.)
Brucella abortus has a special affinity for the pregnant endometrium and
fetal placenta, but does not persist well in the nonpregnant uterus (a few
weeks in most cases).
(Pathogenesis of Caruncles Infection)
In pregnant animals,
B. abortus is carried by the bloodstream to the fetal caruncles. The
bacteria replicate in placental trophoblasts and are released into the fetal
chorionic villi and finally enter the fetal circulation. The intrauterine
lesions apparently progress very slowly, because an interval of many
months may elapse between infection and, depending on the severity of
the placental lesions, abortion (most often in the seventh or eighth month
of pregnancy), premature birth, or birth at term of a viable or nonviable
calf.
Lesions
occur in the uterus, placenta, and fetus. There are mild to
severe endometritis and a more-or-less abundant, odorless, seropurulent
exudate between endometrium and chorion.
Placental lesions
are not
uniform and typically are more severe over the placentomes than in the
intercotyledonary regions. They include necrosis of cotyledons which
may vary from mild to severe, and edema and thickening of
intercotyledonary regions. The placenta is usually retained.
Fetal lesions
include blood-tinged fluid in subcutis and body cavities and a
bronchopneumonia of variable severity.
* Brucella suis in pigs
This strain has more tendency than other strains to produce
widespread lesions. Focal granulomas with necrosis occur in many
organs: female and male genitalia, skeleton (typically, the lumbar region
Systemic Pathology Lecturer- Female Genital System - Dr. Saevan S. Al-Mahmood
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of the vertebral column), synovial structures, mammary glands, lymph
nodes, spleen, liver, kidney, bladder, and even brain. Pregnancy is not a
prerequisite for uterine infection, and a chronic granulomatous
endometritis can develop. Abortion usually occurs between the second
and third months of pregnancy, but the incidence is less than in the
bovine disease. There is also a high incidence of stillborn and weak
piglets born at term, and probably also a high incidence of early
embryonic deaths.
* Brucella ovis in sheep
Epididymitis in rams is the more common and
important manifestation of this infection.
* Brucella melitensis
in goats resembles bovine brucellosis.
* Brucella canis
in dogs causes abortion and epididymitis. The incidence
in the United States varies between 0.5 and 5%.
2- Chlamydophila abortus
This bacterium is an important cause of in utero infection in sheep
and goats, resulting in abortion (usually in the final trimester of
pregnancy), stillbirth, or the birth of weak lambs. It can also cause
abortion in women in close contact with these aborting ruminants. On
entry into sheep and goats, C. abortus may infect the intestine
permanently, and from here invade the bloodstream and infect the
placenta and frequently the fetus of pregnant animals. Gross placental
lesions resemble those of bovine brucellosis, except that there is almost
equal involvement of cotyledons and intercotyledonary regions. Cattle
can also carry Chlamydophila in their intestine, and the organism can
produce sporadic abortions.
3- Arcanobacterium pyogenes
(Pathogenesis of Infection)
Infection by this bacterium is one of the
most common causes of sporadic abortion in cattle. The bacterium is a
common contaminant on mucous membranes and is found in the tonsils
and vagina of healthy cattle. It may penetrate the bloodstream from a
mucosal surface, resulting in transient bacteremia which, in a pregnant
animal, may result in placental localization and abortion. (This may
happen if the animal immune system is temporarily weakened, for
example because of some stressful episode, physical or otherwise.)
Abortion may occur at any stage of pregnancy but is usually in the last
trimester. Dams may be ill following abortion, and some die with
suppurative endometritis, arthritis, or mastitis.
Systemic Pathology Lecturer- Female Genital System - Dr. Saevan S. Al-Mahmood
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Arcanobacterium pyogenes
as a cause of abortion in cattle and
sheep.
The Gross lesions
can visible in the placenta, trachea and lung. (1)
the placenta may be retended, (2) marked autolysis and suppurtive
placentitis with yellow to brown exudate with smeller and edematous
cotyledon, (3) hemorrhagic cast present in the trachea, (4) lung is dark red
and swollen with yellow foci visible on the surface.
Microscopically
lesion may be modest with large number of
bacteria, but no inflammatory cells in the placenta or excessive (with
sever necrotizing suppurtive process in the placenta.
2- Noninfectious diseases
A- Hydramnios (hydrops of the amnion)
Is excessive accumulation of fluid in the amniotic sac. It is usually
associated with malformations of the fetus, especially those involving
gross facial anomalies. Normally, the amniotic fluid consists largely of
fetal salivary secretion, the volume being largely controlled by fetal
swallowing, which begins at a very early age.
B- Hydrallantois
Is excessive amount of fluid in the allantoic sac. It results from
abnormal function of the placentomes due to inadequate numbers of
caruncles and development of adventitial placentation. Normal allantoic
fluid is derived from the fetal kidney via the urachus. The quantity of
excess fluid in hydrallantois may be as much as 170 litres, which may
lead to ventral hernia or rupture of the prepubic tendon and to abortion or
dystocia with uterine paresis, retention of placenta, and metritis.
C- A Freemartin or Free-martin
Is an infertile female mammal which has masculinized behavior and
non- functioning ovaries. Genetically and externally the animal is female,
but it is sterilized in the uterine by hormones from a male twin, becoming
an infertile partial intersex. Freemartins is the normal outcome of mixed –
sex twins in all cattle species and also occurs in other mammals including
sheep, goats and pigs. If anastamosis fail to develop the female not
damaged but all female – male cattle result in the female freemartin,
because of the clear association between freemartin and the presence of
interplacental anastamosis and because the male gonads develop earlier
than those of the female. It was present that male sex hormones were
carrier from male to female fetus sterilizing and modified the female.
Androgen can musculinized the female but they can't inhibit the ovary or
nasonephric duct.
Mechanisms:
in most cattle twin, the blood vessels in the chorions
become interconnected, allowing blood from each twin to flow around the
Systemic Pathology Lecturer- Female Genital System - Dr. Saevan S. Al-Mahmood
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other. If both fetus are the same sex this is of no significance, but if they
are different, mal-hormones pass from the male twin to the female twin,
the male hormones then masculinized the female twin and the result is a
freemartin. The degree of masculinization is greater if the fusion occurs
earlier in the pregnancy. The male twin is largely unaffected by the
fusion, although the size of testicles may be slightly reduced. Testicle size
is associated with fertility, so there may be same reduction in bull
fertility.
VI- Abnormalities of Mammary Gland
MASTITIS
Most of what is known about mastitis pertains to dairy cattle. The
most common route of invasion of the mammary gland by
microorganisms is through the teat canal. This structure is therefore a
primary and critical barrier to infection.
The teat canal is lined by keratinized stratified squamous epithelium
which is covered by a layer of „smegma‟ , a waxy material probably
composed of epithelial debris and milk solids that may be inhibitory to
bacterial growth. The teat canal also has a sphincter that closes after
milking.
Mechanical injury to the teat end from improper use of milking
equipment can be an important contributor to ascending bacterial
infection of the mammary gland by reducing the amount of smegma (e.g.
through over milking) or by causing partial eversion of the teat canal,
ulceration, and fibrosis, thus leading to incomplete closure of the
sphincter.
Other natural defense mechanisms of the normal mammary gland
include:
1- Flushing action of milk.
2- Humoral factors that are inhibitory to bacterial growth: lactoferrin,
lysozyme, lactoperoxidase, immunoglobulins (IgG, IgM).
3- Cellular factors: macrophages, neutrophils, natural killer cells.
Infectious agents of bovine mastitis can be divided into three general
groups:
1- Those for which the mammary gland is the natural reservoir and that
are transmitted from cow to cow in a contagious manner, e.g.
Streptococcus agalactiae, some strains of Staphylococcus aureus,
and Mycoplasma spp.,
2- Those that are acquired by contamination of the teats from an
unhygienic external environment, e.g. Coliform bacteria,
Pseudomonas spp., the alga Prototheca zopfii,
Systemic Pathology Lecturer- Female Genital System - Dr. Saevan S. Al-Mahmood
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3- Those that are capable of persisting in either location, e.g. Strept.
dysgalactiae, Strept. uberis.
Peak occurrence of mastitis is shortly after calving and in the drying
off period when milk stagnates in the udder, thus leading to a buildup of
microorganisms. With most infectious agents.
The pathogenesis
includes
entry into the streak canal, multiplication of organisms in the canal, and
invasion of mammary tissue. This is followed by an acute inflammation
of the ducts and alveoli and interstitial edema. Lesions may progress to
necrosis or formation of abscesses and then fibrosis, depending on the
virulence of the agent. Inflammatory swelling or fibrosis can obstruct
milk flow in adjacent lobules, leading to premature (but reversible)
involution of portions of the gland. Depending on the degree of injury,
healing can be by regeneration, fibrosis, sequestration of necrotic parts, or
sloughing of gangrenous parts.
A) Streptococcus agalactiae
The mammary gland is the sole natural habitat of this bacterium, its
resistance to the extramammary environment is low. Streptococcal
mastitis is usually permanent. Infection typically results in periodic flare-
ups of bacterial proliferation that induce multifocal areas of acute but
relatively mild inflammation of the mammary parenchyma followed by
extensive fibrosis of repair, there is also stagnation of milk leading to
induration of the gland and involution of glandular tissue.
Natural resistance to mastitis caused by this bacterium is stronger in
some cows than in others, although it generally declines with age. The
composition of the smegma in the teat canal appears to determine this
variation in resistance to the bacterium among cows.
B) Staphylococcus aureus
The skin and mucous membranes are the natural permanent habitat of
pathogenic strains of this bacterium, although it is able to resist for some
time in the general environment. Infection of the mammary gland can be
peracute and fulminating, the bacteria producing a toxin that causes
severe inflammation, necrosis and gangrene of the affected quarters
accompanied by high mortality. This type of infection typically occurs
shortly after parturition. If the animal survives, natural separation of the
gangrenous areas begins after about a week. More commonly, the
infection is milder and more chronic, progressing in a manner comparable
to infection by Strept. agalactiae, but causing a more intense
inflammation with the production of multiple pyogranulomas (so-called
“botryomycosis”).
Systemic Pathology Lecturer- Female Genital System - Dr. Saevan S. Al-Mahmood
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C) Coliforms (including
Escherichia coli
,
Klebsiella
spp,
Citrobacter
spp,
Enterobacter
spp. and
Serratia
spp.,
Proteus
spp.)
These organisms, especially E. coli, can produce a clinically acute
disease with systemic signs of severe endotoxemia and, possibly,
septicemia. The disease can be fatal within 8 hours. This form is most
commonly seen shortly after parturition. The inflammation may be serous
with much edema, or it may be severely hemorrhagic. Bacterial
endotoxins damage the microvasculature of the alveolar walls and
mammary interstitium, which results in extensive necrosis of the
mammary tissue if the animal survives beyond 1-2 days, gangrene is not
produced by coliform bacilli alone. If the animal survives longer, the
necrotic tissue, usually involving one quarter, becomes sequestered.
Coliform bacteria, mainly those other than E. coli, can also cause a
milder, progressive type of disease resembling that caused by Strept.
agalactiae, especially during the nonlactating period.