Reproductive Pathology Female Tract (2)

Pathology of the Vagina & Vulva
1. Congenital Defects
  1. Usually as part of intersex/failure of fusion of Paramesonephric ducts with urogenital sinus
2. Trauma
  1. Prolapse
    1. Ewe: Late pregnancy, Oestrogenic pasture
    2. Bitch: (Boxer - Oestrus)
  2. Rupture
    1. Parturition
3. Mechanical
  1. Parturition
4. Infectious
  1. Cattle: Infectious pustular vulvovaginitis
    1. Bovine herpesvirus type 1 (Bovine viral rhinotracheitis)
      1. Hyperaemia & Oedema
        Increased lymphoid nodules
        Ulceration
  2. Horses: Contagious equine metritis
    1. Tayorella equigenitalis
      1. Resides in crypts/fossa around the clitoris
5. Neoplasia
  1. Squamous Cell Carcinoma
    1. Cow, Ewe, Mare
    2. Solar radiation
  2. Canine transmissible Venereal Tumor
    1. Bitch
    2. Transmitted at coitus
      1. Transfer of intact cells
        Spontaneous regression
    3. Grossly: Nodular, friable, ulcerated
    4. Histologically: Sheets of round cells
    5. Uncommon unless Dogs are free-ranging
  3. Spindle Cell Tumors
    1. Leiomyoma: Smooth muscle
      1. Fibroma: Fibroblasts
        Lipoma: Adipocytes
        Equine sarcoid
  4. Melanotic tumors: Melanocytomas
    1. Grey Horses: Vulva of Mares
Pathology of Pregnant Uterus
1. Anatomy of the Placenta
  1. Mare, Pig: Diffuse Placenta
  2. Dog, Cat: Zonary Placenta
  3. Ruminants: Cotyledonary Placenta
2. Normal Structures Present During Pregnancy
  1. Corpora Lutea
    1. Ovaries: Secrete Progesterones
      1. Maintain pregnancy for varying lengths of time
  2. Endometrial Cups
    1. Mares
    2. Develop from foetal tissue
      1. Visible from day 40: Pale
        Start to slough from day 100
        Produce Gonadotrophic hormones
  3. Amniotic Plaques
    1. 2-4 mm plaques of squamous epithelium
  4. Placental Mineralization
    1. Milky deposition of Ca2+ mid-pregnancy
      1. Small bony plaques may form in allantochorion
  5. Calcified yolk sac remnants
  6. Hippomanes
    1. Mare
  7. Cervical Star
    1. Mares: Placenta adjacent to cervix
3. Responses to Disease/Infection (During Pregnancy)
  1. Death of the Embryo/Early Fetus & Reabsorption
    1. Early embryotic death & return to Oestrus
  2. Foetal mummification
    1. No bacterial infection
      1. Fluids reabsorbed
        Foetus retained as black leathery mass
    2. Takes 6-8 months (Bovine), 8-12 weeks (Swine)
    3. Sow: Porcine parvovirus (SMEDI: Stillbirths, Mummified piglets, Embryonic deaths, Infertility)
    4. Cow: Bovine Viral Diarrhoea virus (Pestivirus)
    5. Mare: Twinning, Premature placental separation, Torsion of umilical cord (slowly developing ischaemia)
  3. Maceration & Emphysema
    1. Uterine infection early in pregnancy => Maceration & expulsion
      1. Endometritis & Pyometria also present
        Emphysema occurs when dead foetal tissue is invaded by putrefactive bacteria (Clostridia)
  4. Abortion
    1. Expulsion of foetus before its viable
      1. 2ndary to foetal death due to damage to uterus, placenta or foetus
  5. Stillbirth
    1. Death at birth after age at which foetus is potentially viable
  6. Live birth
    1. Birth of normal or abnormal neonate
  7. Congenital malformation
    1. Genetic factors:
      1. Inherited of Acquired
        Ovine: Additional forelimb, Arthogryposis, Hydrocephalus, Cerebellar hypoplasia
        Cow: 2 heads
        Porcine: Cyclops & meningocoele
    2. Environmental factors:
      1. Physical, Chemical, Nutritional, Hormonal, Infectious agents
  8. Retained foetal membranes
    1. Metritis/ Endometritis
4. Non-infectious Conditions (Pregnant Uterus)
  1. Rupture
    1. Usually during parturition as a result of untreated or mishandled dystocia
  2. Ventral herniation
    1. Muscle weakness, old age, trauma
    2. Heavily pregnant uterus can herniate through abdominal muscle wall lateral to mid-line
    3. Cow & Mare
  3. Adventitial Placentation
    1. Formation of additional (less efficient) sites of placentation between existing placentomes
    2. Congenital or due to loss of Carnucles as a result of previous endometritis
    3. Cattle: Normally cows have 75-120 Carnucles
    4. If marked => Pregnancy is insecure & may abort mid-term
  4. Hydramnios
    1. Accumulation of excess fluid in amniotic sac
    2. Associated w/ foetal abnormalities (especially facial abnormalities
  5. Hydrallantois
    1. Accumulation of excess fluid in allantoic sacs
    2. Adventitial placentation or twin pregnancy
  6. Anasarca
    1. Either Hydrallantois or Hydramnios may be associated with accumulation of fluid in foetus
    2. Mainly Cattle (Rare in other species)
  7. Prolonged Gestation
    1. Foetal malformation
      1. Absence of pituitary gland
        Holstein, Guernsey cattle
      2. Anencephaly
    2. Disturbance of foetal pituitary adrenal axis
      1. Failure of release of foetal corticosteroids
        Failure of induction of parturition
5. Routes of Infection of Uterus
  1. Vagina & Cervix
    1. Mare: Bacteria & fungi
    2. Bovine: Campylobacter fetus subsp. venerealis
  2. Haematogenous
    1. Via maternal circulation (Bacteraemia/viraemia)
    2. Transplacental
    3. Abortion may occur as a result of:
      1. Endotoxins or pyrexia
        Leptospira interrogans: Pigs, Cattle
        Salmonella enterica: Cattle & Sheep
        Few or no lesions in placenta or foetus, though bacteria present
      2. Immediate Placentitis
        Campylobacter fetus subsp. fetus: Cow
        Listeria spp.: Sheep
        Lesions in foetus & placenta (Cotyledon)
        Abortion ~ 2 weeks after oral infection
      3. Delayed Placentitis
        Brucella abortus: Cows
        Chlamydrophila abortus: Sheep
      4. Direct Damage to Foetus
        Bovine viral diarrhoea virus
        Porcine parvovirus
        Bovine herpesvirus type 1
        Infectious bovine rhinotrachacheitis
        Infectious pustular vulvovaginitis
        Abortion, Foetal death, Congenital abnormalities, Persistent infection of neonate
6. Viral Infections
  1. Infectious Bovine Rhinotracheitis
    1. Bovine herpesvirus type 1
      1. Abortion late in gestation (3-6 weeks after exposure), soon after foetal death
        Foetus may be autolysed
        Intranuclear inclusions in liver
  2. Bovine Viral Diarrhoea Virus
    1. Pestivirus
      1. Abortion of fresh, autolysed or mummified foetuses
        Calves may also be born alive (weak & uncoordinated due to cerebellar hypoplasia)
  3. Border disease virus
    1. Pestivirus
      1. Occasional abortion of foetus (sometimes w/ anasarca)
        More frequently => "Hairy shakers" (small, weak, hairy lambs with skeletal abnormalities)
  4. Porcine Parvovirus
    1. SMEDI syndrome
  5. PRRS
    1. Abortion late in gestation
      1. Interstitial pneumonia in live piglets
  6. Feline panleucopaenia virus
    1. Cerebellar hypoplasia (kittens)
7. Bacterial Infections
  1. Brucella abortus
    1. Cows
    2. Transmission by ingestion
      1. Abortion occurs in last half of pregnacy
    3. Placenta is covered by fibronecrotic tissue
      1. Foetus => Bronchopneumonia
  2. Listeria spp.
    1. Cattle & Sheep
    2. Abortions in last 3rd of pregnancy
      1. Foetal membranes often retained => Metritis
        Placenta covered by purulent exudate
        Focal yellow lesion in foetal liver
  3. Campylobacter fetus subsp. fetus; C. jejuni
    1. Sheep
    2. Abortion storms
      1. Oral transmission: Faeces or aborted material
        Late abortion, premature & weak lambs
        Areas of focal hepatic necrosis in liver
  4. Coxiella burnetii
    1. Sheep, rarely cattle
    2. Infection by inhalation, ingestion or tick bites
      1. Late abortion or birth of weak lambs/kids
        Thickened leathery placenta covered in exudate
        Ziehl-Neelsen stain for organisms
  5. Chlamydophila abortus: Enzootic abortion of Ewes
    1. Sheep: Late abortion/premature lambing
      1. Retained foetal membranes
        Infection by ingestion
        Immunity develops following exposure: Abortion only in Ewes not previously exposed
    2. Aborted fetus: Oedematous, blood tinged fluid in body cavities
    3. Cotyledons: Necrotic, covered with exudate
    4. Foetal membranes: Thickened, oedematous
8. Protozoal Infections
  1. Toxoplasma gondii
    1. Sheep: Abortion late in gestation
    2. Infection with oocysts from cat feces
      1. Ewes not clinically ill
        Foetus usually has no gross lesions
    3. Necrotizing placentitis: Cotyledons: Bright red; multiple (1-3mm diameter), white/yellow foci
  2. Neospora caninum
    1. Cattle
    2. Late abortion
      1. Mummified or autolysed foetus
        Foetal malformation: Arthrogryposis
  3. Trichomanas foetus
    1. Cattle
    2. Venereal infection
      1. Early embryonic death & infertility
9. Mycotic Infections
  1. Aspergillus spp; Mucor/Rhizopus/Absidia spp.
  2. Cattle, Sheep, Goats, Horses
  3. Abortions: Individuals rather than outbreaks
  4. Runminal ulcers -> Infected w/ the fungus -> Haemotogenous spread to uterus
  5. Abortion late in pregnancy
    1. Placenta often retained
      1. Leathery thickening may affect whole placenta
        Raised grey/white plaques on skin of foetus
Pathology of Mammmary Glands
1. Anatomy of Mammary Glands
  1. Modified sweat glands (Nourishment - Milk & Igs - Colostrum)
  2. Composed of alveoli arranged into lobules which are in turn arranged into lobes
  3. Udder = MG & teats together (Ewes, Cows, Mares & Sows)
  4. Mammary Gland = Secretory & Duct system associated with 1 teat
  5. Route of Milk Flow out of Mammary Gland
    1. Alveoli -> Ducts (acinar, lobular, major) -> Gland cistern/sinus -> Teat cistern/sinus -> Streak canal
  6. Lymphatic Drainage
    1. Caudal mammary glands => Superficial inguinal lymph node
      1. Cranial mammary glands => Axillary or Sternal lymph nodes
  7. Physiology
    1. Subject to cyclical hormonal control
      1. Before puberty -> Mammary fat pad w/ simple ducts
        After puberty -> More obvious growth of duct system
        During pregnancy -> Proliferation of glandular epithelium
2. Congenital Conditions
  1. Galactorrhoea ("Witch's milk")
    1. Neonatal animals may secrete fluid/milk from their mammary glands (Due to effects of maternal hormones on the foetal pituitary)
      1. Bitches that have undergone ovariohyterectomy during Dioestrus (Due to a prolactin surge)
  2. Malformations (Usually teats - Aplasia, Hypoplasia, Inversion, Fistulae, Non-patency)
    1. Significance depends on whether animal will be used for breeding/milk production
  3. Supernumerary teats (esp. cattle)
    1. May interfere with attachment of the neonate or milking machines
  4. Pigmentation (melanosis in pigs)
    1. Usually disappears following first lactation
3. Bovine Herpes Mammilitis
  1. Inflammation of the SKIN of the teat & udder
  2. Bovine Herpes Virus type 2
  3. Sporadic & 2ndary to trauma
    1. Teat swelling & pain (reluctance to milk -> contributes to 2ndary mastitis)
  4. Grossly: Plaques (1-2cm) w/ central necrosis, ulcers +/- crusts & regional lymphadenopathy
  5. Histologically: Epithelial syncytia with intranuclear eosinophilic inclusion bodies
4. Mastitis
  1. Inflammation of Mammary Gland
  2. Cow "Model" species
  3. Usually due to invasion of gland by bacteria:
    1. Haemotogenous
    2. Percutaneous
    3. Invasion of teat canal (Most common)
      1. Critical barrier to infection (If damaged, Ex. over-milking, it will allow ascending infection)
    4. Streptococcus, Staphylcoccus & E.coli
  4. Acute, subacute & chronic infections may have different implications clinically & pathologically
  5. Pathogenesis:
    1. Trauma & cell damage
      1. => Invasion of Udder & bacterial proliferation
        => Tissue penetration, Inflammation (-> Exudation) & Epithelial cell death (-> Desquamation ) => Clots in milk
        => Clinical mastitis & clinical sequelae
        Neutrophils migrate into the milk (Resolution or Fibrosis - continued cell damage, replacement of mammary tissue)
  6. Overcoming barriers to infection
    1. Streak canal: Bacteria can multiply along the streak canal just after milking
      1. Vacuum fluctuations can propel bacteria into teat sinus during milking
        Bacteria the must overcome immune defence of Cow
  7. Bacterial Virulence Factors
    1. Pore-forming toxins (cytoplasm leaks)
      1. Enzymatic toxins
        Induction of apoptosis of host cells (protein translocation)
    2. Ex. E.coli: Proteinases (collagenolytic enzymes)
      1. S.aureus: Toxin that destroys cell membranes, damaging milk producing tissue
  8. Classifications
    1. Patterns of Mastitis
      1. Acute Catarrhal
        Often sub-clinical & may become purulent -> chronic (with fibrosis) Ex. Streptococcus
        Hyperaemia, Interstitial oedema, lymphatic dilation & migration of neutrophils into interlobular tissue & alveoli
      2. Acute Suppurative
        Ductal & local tissue involvement with pus formation Ex. Staphylcoccus, T. pyogenes (Trueperella)
        Organism survives in the ducts & penetrates the connective tissue with production of purulent material
      3. Necrotising
        T. pyogenes, S.aureus, Streptococcus
        Organism or toxin penetrates & causes acute necrosis => (May) Death - Toxaemia
      4. Endotoxic Shock Syndrome
        E.coli
        Often associated with necrotising vascular damage due to endotoxic injury
        Peracute with Serous inflammation & Oedema or possibly Haemorrhagic inflammation
      5. Granulomatous
        Staphylcoccus, T.pyogenes, Mycobacteria, Actinobacillus
        Invasion deep into tissue => Persistent foci of infection with subsequent granulomatous inflammation
      6. Pathogenesis (Acute Catarrhal/Suppurative:
        Hyperaemia of sinus mucosa
        => Bacteria invade alveoli
        => Interstitial Oedema, Neutrophils in alveoli & interstitium, Epithelial sloughing, Involution
        => Periductal fibrosis & granulation tissue within ducts (Chronic stage)
  9. Other Types of Bovine Mastitis
    1. Summer Mastitis
      1. T. pyogenes 2ndary to penetrating injury (Often mixed growth is cultured) => Necrotising & suppurative inflammation targeting the ducts (galactophoritis)
    2. Tuberculous mastitis
      1. M. bovis (Haemotogenous spread)
    3. Mycoplasma mastitis
      1. Sudden agalactia, Hard to firm, swollen, painless udder
    4. Fungal, Yeast, algal infections
  10. Pathogens
    1. Gram +ve Pathogens
      1. Acute necrotising mastitis
        Chronic Suppurative mastitis
        Start as Acute Catarrhal (Strep) or acute suppurative (Staph, T.pyogenes)
        Staph or T. pyogenes
    2. Gram -ve Pathogens
      1. Systemic Illness
      2. Enter glands -> Produce Endotoxins (LPS)=>Binds TLR4 & CD14 => Cytokine & Interleukin release => Tissue necrosis & vascular leakage
  11. Ovine Mastitis
    1. Predisposing Factors:
      1. 1) Trauma: Teat & udder injury
        2) Udder chilling: Wet & cold conditions
        3) Lamb -sick fields: Bacterial reservoir
    2. Pathogens
      1. Most common:
        Staphylcoccus aureus (similar to bovine)
        Mannheimia haemolytica (often near end of lactation)
        => Acute necrotising or Gangrenous mastitis so clinical presentation is often sudden, unexpected death
        Typically only 1 gland is affected with Acute necrotising disease (enlarged, tense gland which may be discolored blue with watery milk expressed)
      2. Others: Corynebacterium pseudotuberculosis, T.pyogenes
        Focal abscesses possibly due to skin wounds
      3. Mycoplasma agalactiae
        Goats & Sheep
        Septicaemia (often fatal) => keratoconjunctivitis, arthritis, mastitis
      4. Viral Mastitis
        Sheep: Maedi-visna virus
        Pneumonia (lungs - ovine progression pneumonia), Encephalitis (visna), Lymphoplasmacytic mastitis
        Goats: Caprine arthritis & Encephalitis
    3. Classifications
  12. Porcine Mastitis
    1. Intensive breeding units
    2. Acute infections (E.coli - post-parturition)
    3. Chronic Granulomatous mastitis (S.aureus)
    4. Mastitis -metritis-agalactia syndrome
      1. Lethargy, pyrexia, firm, swollen mammary glands & agalactia
        Multiple possible causes (Infection or hormonal dysfunction due to management changes)
      2. 12- 48 hrs post-partum
  13. Mastitis in Dogs & Cats
    1. Often non-specific, acute disease in lactating animals (may be seen in pseudopregnant animals)
    2. Streptococcus & Staphylcoccus spp. usually involved
5. Mammary Neoplasia
  1. Common: Dog & Cat
  2. Rare: Other species
  3. Can occur in males
  4. Benign or malignant w/ marked variation in histological appearance & behavior
  5. NON -neoplastic Conditions:
    1. 1) Mammary ductal & lobular hyperplasia:
      1. Hyperplasia of intraductal epithelial cells & secretory acini
      2. Bitches & Queens
      3. May be Pre-neoplastic
    2. 2) Mammary Fibroepithelial hyperplasia
      1. Young (<2 yr old), cycling or pregnant Queens, or Induced via synthetic progestagens
      2. Can regress spontaneously or require ovariohisterectomy
      3. Grossly: Marked swelling of mammary tissue w/ erythema +/- ulceration & necrosis
      4. Histologically: Proliferation of well differentiated ductular epithelium & stroma with marked stromal oedema
    3. Present as mammary masses
  6. Canine mammary neoplasia
    1. Common (50% of neoplasms in Bitch)
      1. Cocker spaniels, terriers, poodles
    2. Age: 6-13+ yrs
    3. Location: 70% in caudal glands (glands 3-5), may be multifocal
    4. (50%) Malignant tumors: metastasize to lungs & lymph nodes
    5. Hormonally dependent
      1. Ovariohysterectomy prior to 1st Oestrus markedly reduces the risk of mammary neoplasia
      2. Effect of ovariohysterectomy at time of Dx unclear
    6. Benign: Simple/complex adenomas (Acinar epithelial componenet & Spindle shaped myoepithelial component), Fibroadenomas, Mixed tumors (have cartilage &/or bone)
    7. Malignant: Ductular carcinoma, Simple/complex carcinoma; Primary Mammary sarcomas - less common- (osteosarcoma, fibrosarcoma, chondrsarcoma, liposarcoma)
      1. Clinical Signs:
        Rapid growth
        Ulceration
        Local lymphadenopathy
        Systemic illness/dyspneoa
    8. Inflammatory mammary carcinoma
      1. Rare, locally aggressive tumor
      2. Poor response to Tx
        High grade mammary carcinoma w/ involvement of dermal lymphatics
        May mimic dermatitis/mastitis macroscopically
  7. Feline Mammary Neoplasia
    1. Less common than Dogs
    2. Age: 5-15+ yrs
    3. 80 - 90% are malignant (Metastases to LN, lung pleura, liver, spleen, adrenal glands & kidney)
    4. Diffuse mammary fibroepithelial hyperplasia
      1. NON-neoplastic

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Reproductive Pathology Female Tract (2)

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	Created by melian.yates over 10 years ago