Repro pathology 1

At what different levels is sex defined?

• Chromosal —> XX/XY

  • Sex determining region of Y (SRY makes male)

• Gonad —> if under influence of SRY develops into testes if not ovaries

• Hormonal profile —> affects tubular genitalia and external genitalia

• Tubular (internal) genitalia

• External genitalia

All of these above constitute sex of aniamal

What are the ducts that run from gonad to urogenital sinus?

• Paramesonephric duct

  • Female progresses in uterine tube

  • Regresses in males

• Mesonephric duct

  • Male progresses into ductus deferens

  • Regresses in females

What does the urogenital sinus develop into?

Urinary bladder and either male and female genitalia

What is intersex vs hermaphroditism?

• Intersex = ambiguous / atypical genitalia

• Hermaphroditism = presence of both ovarian & testicular gonadal tissue

What are the 3 major categories of disorders of sexual development (DSD)?

• Abnormal / missing chromosome

• DSD with normal female karyotype (XX)

• DSD with normal male karyotype (XY)

What are the two sex chromosal disorders?

• XO (Turner syndrome) or XXX —> females with severe ovarian dysgenesis, hypoplasia & immature repro tract

• XXY (Klinefelter syndrome) —> males (phenotypically) with testicular hypoplasia e.g. male tortoiseshell cat

What is XX DSD?

• XX [SRY negative] —> ovotesticular

• Usually true hermaphrodite

• Phenotypically female w/ masculinisation

What is the origin of XX DSD

• Inherited in American cocker spaniel (AR)

• Associated with the polled gene in goats (polled intersex syndrome – PIS)

What are the two types of XY DSD?

• XY SRY-positive:

  • Testicular DSD w/ female phenotype (male pseudohermaphrodite)

    • androgen insensitivity, lack of AMH (anti-mullerian hormone)

• XY SRY-positive:

  • Testicular DSD w/ male phenotype e.g. cryptorchidism (testes don’t descend i.e. remains in abdomen)

What is freemartinism?

• Form of ovarian dysgenesis in cattle

• Sterile female twin from a set of heterozygotic twins

• Fusion of placental vessels and sharing of blood between twins during early embryonic developement

• Humoral substances (testis determining factor, AMH) from blood of male twin to female, ovarian inhibition of female twin

  • Male unaffected

    

What are the presenting features of freemartinism?

• Hypoplastic uterus and ovaries

• Hypoplastic vulva

• Presence of bulbourethral and vesicular glands

What are the categories of ovarian pathology?

a) Ovarian circulatory disorders

b) Cystic ovarian disease

c) Ovarian neoplasia

What are the ovarian circulatory disorders?

• Intrafollicular haemorrhage

• Traumatic haemorrahge

What is intrafollicular haemorrhage?

• Physiological haemorrhage —> during ovulation

  • very occasionally —> severe, even lethal (mare)

When does traumatic haemorrhage occur in the ovaries?

• Due to manual enucleation of corpus luteum or cysts (cattle; now rare, more common before prostaglandins etc. were available)

What is being shown here?

• Enucleation haemorrhage, cow

  • Blood clot in ovarian bursa

  • Large blood clot (haematoma) containing an enucleated corpus luteum located near the cervix (bottom R)

What are follicular cysts

• Arise from secondary follicles that fail to ovulate, involute or luteinise

• Also caused by failure in LH release during oestrus

In what animals are follicular cysts seen?

Common in cattle and pigs + seen in dogs, cats, sheep + goats; very rare in horses

How do follicular cysts present?

• Non cyclic oestrogen secretion → fail to come back into oestrus or persistent bulling

• Continuous oestrus, cystic endometrial hyperplasia

What can multiple follicular cysts cause in cattle? (polycystic ovarian disease)

Hyperestrogenism

• Which can lead to behavioural changes e.g. nymphomania

• Persistent bulling

What is being shown here?

Polycystic ovarian disease —> Follicular cysts

• Fluid filled

• Palpation

What animals is ovarian neoplasia most common in?

Cows, mares, bitches

What cell types does ovarian neoplasia orginate from?

• Surface epithelium

• Ovarian stroma

• Ovarian germ cells (give rise to eggs)

What ovarian neoplasias arise from surface epithelium?

• Papillary cystadenoma

  • Most common in bitches, can be multicentric + involve both ovaries

• Papillary cystadenocarcinoma

  • Occurs in older bitches

  • Invasive growth

    • Implantation on peritoneum

    • Invasion & obstruction of lymphatic vessels & veins

  • Ascites

  • Widespread distant metastases

What is the DDx for papillary cystadenocarcinoma?

Mesothelioma

What is being shown here?

Papillary cystadenocarcinoma - GSD

• 'finger like projections'

• haemorrhage because malignant

What tumour arises from the gonadal stroma?

Granulosa cell tumours

• Most common ovarian neoplasia in cows, mares and older bitches

How do granulosa cell tumours present in cows and mares cf to dogs and cats?

Cow, mare:

• Usually unilateral, benign, often very large

• Hypersecretion of progesterone, oestradiol and/or testosterone

  • increased testosterone release causes masculinisation of males if granulosa cell tumour

Dogs, cats:

Often associated with hyperoestrogenism

What is being shown here?

Granulosa cell tumour

• Highly cystic look

• Can be very big

• Benign but space occupying can compress nearby organs

How does the histology of a GCT present?

• Large cystic spaces

  • centrally cystic

• Granulosa cells line these (many layers) → distended follicles

What ovarian neoplasm originates from germ cells?

Dysgerminoma

• Occur in older bitches

• Usually unilateral

• Approx 20% metastasise to regional LN & transceolomically

• (Female counterpart to testicular seminoma in males)

Teratoma

• Germ cells differentiating into multiple lineages

(spay / castration usually curative if benign)

What is being shown here

Dysgerminoma —> bitch

How do dysgerminoma present?

Pleomorphic & heterogenous (big atypical cells)

• But still rarely malignant

What is being shown here?

Benign teratoma

hair + teeth seen

How does a benign teratoma present histologically?

Different tissues (e.g.—> tooth, bone, cartilage and skin)

due to being pleuripotent i.e. can differentiate into any ectoderm, endoderm, mesoderm

What acquired abnormalies can affect the uterine tubes?

Salpinx = pertains to uterine tubes

Hydrosalpinx —> clear fluid in tubes, due to obstruction either at abdominal or uterine ostium.

Salpingitis —> inflammation due to ascending infection (cattle)

Pyosalpinx —> pus in tubes

What are the categories of pathology that affect the uterus?

a) Displacement of uterus

b) Disorders of endometrial growth

c) Inflammation of the non-gravid uterus

d) Primary tumours of the uterus

e) Diseases of the gravid uterus

What can cause displacement of the uterus?

• Torsion —> long tubular organs twist around their own long axis

• Uterine prolapse

• Rupture

What causes torsion?

Usually gravid uterus

• Multiparous animals —> can be in one horn

• With relaxation of uterine bands and foetal movements

What are the consequences of uterine torsion in cattle?

• Whole organ

• Leads to congestion

• Haemorrhagic necrosis

• Foetal death

What is uterine prolapse associated with in ruminants?

Post-parturient ypocalcaemia / dystocia

When does uterine rupture usually occur?

After obstetrical manipulation —> middle uterine artery susceptible to damage → rupture = severe bleedout

be gentle & use flats of hands rather than points of fingers

What are the different disorders of endometrial growth?

• Endometrial hyperplasia

  • Oestrogen mediated

  • Progesterone mediated

What causes endometrial hyperplasia?

• Excessive/ prolonged female hormonal stimulation

  • Ungulates, rodent —> oestrogens

  • Dog, cat —> progesterone acting on oestrogen-primed endometrium

What causes oestrogen mediated endometrial hyperplasia?

• Prolonged non-cyclic oestrogen stimulation (e.g. ovarian follicles)

• Excessive levels of circulating oestrogens (e.g. granulosa cell tumour)

What are the effects of oestrogen mediated hyperplasia?

• Hypertrophy of myometrium

• Hyperplasia of endometrium → cystic endometrial hyperplasia (uterine glands become enlarged + cystic)

• Hydrometra / mucometra

What causes progesterone mediated endometrial hyperplasia?

• Common in dogs

• In cows —> associated with reatined CL → hyperprogesteronism

What are the consequeunces progesterone mediated endometrial hyperplasia?

• Predisposes uterus to infection and pyometra

• Glandular secretion

• In oestrogen-primed endometrium -> increased synthesis of progesterone receptors + enhanced effect of progesterone

What is being shown in this image=

Cystic Endometrial Hyperplasia —> bitch

• Uterine horns appear diffusely or segmentally enlarged

• Undulation

• On palpation —> cystic structure + fluid-filled

How does cystic endometrial hyperplasia present histologically?

Hyperplastic endometrium with numerous fluid-filled cysts

What are the different terms used to describe inflammation of the non gravid uterus?

• Endometritis (inside)

• Metritis (usually involvement of myometrium)

• Perimetritis (outside)

• Panmetritis (throughout)

non gravid uterus relatively resistant to infection, cervix acts as barrier

What are the sequelae of inflammation of the uterus?

• Septicaemia/toxaemia, pyaemia

  • Esp. if cervix is closed & containing infection inside

• Metritis, pyometra

• Ascending infection (salpingitis = inflam of fallopian tubes; pyelonephritis)

What is pyometria often preceded by?

Mucometra (excessive glandular secretion of mucous)

Define pyometra

Acute / chronic suppurative inflammation of uterus with large quantities of pus in lumen

^^ trichomonas infection

How does pyometra present in dogs and cats?

Bacterial infection of cystic, hyperplastic endometrium

• (“cystic endometrial hyperplasia-pyometra complex”)

What agents cause pyometra in dogs and cats?

Non-specific agent —> E. coli, Proteus, Staphylococcus, Streptococcus

How does pyometra usually present in dogs and cats?

• Generally closed cervix (or with small amount of discharge) → emergency (can lead to septicaemia, septic shock, DIC)

  • open cervix better —> can be drained

What is being shown here?

Pyometra (bitch)

brown viscous exudate

What causes pyometra in cattle?

• Persistent CL due to failure of PGF2a

• Causes hyperprogesteronism

• Decreases myometrial contraction

What is the main agent causing pyometra in cattle?

Tritrichomonas fetus ssp. venerealis,

(+ non-specific agents —> arcanobacterium pyogenes, E.coli, pseudomonas aeruginosa, streptococcus, staphylococcus)

What causes pyometra in mares?

• Postpartum infection independent of persistent CL

  • Often discharge observed

What aetiological agents are commonly isolated in pyometra in mares?

• Streptococcus zooepidemicus

• E. coli

• Pseudomonas aeruginosa

• Klebsiella pneumoniae

• Pasteurella

What are the sequelae of pyometra in cows and mares?

• Resolution (often through vet intervention + PGF2 administration).

• Metritis —> toxaemia/septicaemia

• Rupture with peritioniits

What is being shown here?

Necrotising metritis

What are the primary tumours of the uterus?

• Leiomyoma (most freq uterine neoplasm in SA)

  • Arising from smooth muscle cells of myometrium (also found in vagina & cervix)

  • Benign usually incidental if not overly space occupying

  • Leiomyosarcoma = malignant version, locally invasive

• Adenocarcinoma

  • Epithelial tumour of endometrial glands

  • Freq in rabbits

What is being shown here?

Uterine/vaginal leimyoma

• Smooth raised nodular mass

• If compression of urethral orifice —> bladder distention → hydroureta → hydronephrosis

How does leiomyoma presnt histologically

• Represents smooth muscle cells well

What is being shown here?

Uterine adenocarcinoma

How does uterine adenocarcinoma present histologically?

• Poorly differentiated cells

• Dont recapitulate normally anatomy very well

• Usualy criteria of malignancy

• Acini & tubules that resemble glands

List the diseases of the gravid uterus

• Early embryonic death

• Abortion

• Still birth

• Mummification

• Maceration

What occurs following early embryonic death?

• Resumption of PGF2 synthesis, secretion + restoration of oestrous cycle

• Dissolution + expulsion of embryo

What is early embryonic death usually due to?

Lethal embryonic chromosomal abnormalities

How does abortion differ from stillbirth?

Abortion —> expulsion of embryo / foetus before an age when it could survive

Stillbirth —> expulsion of dead foetus at an age when it could have survived

What are the features of mummification?

• Often absence of intrauterine infection

• Prolonged retention of dead foetus

• Fluids are resorbed, foetal membranes collapse around desiccated, brown-black, leathery mass of dried foetal bones + skin

In what animals is mummification more common?

Multiparous animals

What is being shown here?

Mummification of fetus

What causes maceration and emphysema of foetus?

• Results from intrauterine infection

• In early embryo macerates (and resorbed or expelled)

• Invasion of foetus by gas-forming putrefactive bacteria from vagina (from incomplete abortion → emphysema

• Severe endometritis & pyometra may follow

What is being shown here?

Macerated fetus

• more 'liquidy', purulent & friable than mummification

• foul smelling