• Cystic Endometrial Hyperplasia (CEH) vs Pyometra
  • Two distinct entities
  • CEH
    • From repeated repeated progesterone exposure (cycles)
    • Glands vary in size
    • Glands cystic
    • Sterile fluid - mucometra or hydrometra
    • Not an inflammatory condition
    • Increased progesterone and estrogen receptors
    • Can induce CEH with:
      • Mechanical irritation
      • Biopsy
      • Scarification
      • Silk suture
      • Bacteria
      • Changes reverse if progesterone removed
    • Another form of endometrial hyperplasia
      • As with CEH, it occurs primarily during the luteal phase of the cycle,
      • Endometrium responds to stimuli with a highly organized proliferative remodeling (similar to the normal histology of the endometrium at placentation sites in normal pregnancy)
      • . Although referred to as deciduoma, Schlafer and Gifford propose the use of the term pseudo-placentational endometrial hyperplasia to help distinguish it from CEH
  • Pyometra
    • Complex etiology
      • Hormone
      • Infectious
      • Immunologic
    • Hormone
      • Estrogen and Progesterone not different in pyometra vs. normal cycle
      • Receptors normal (one study found reduced)
      • Estrogen enhances the stimulatory effects of progesterone on the uterus by inducing progesterone receptors.
        • In particular, pharmacological concentrations of estrogen administered during diestrus greatly increases the risk of pyometra.
        • Recent study showed no difference when estradiol benzoate was used for mismate.
      • Bacterial
        • E. coli.
          • Primary
          • 11-20 and 21-30 days post LH primary days of infection
          • Same as intestinal or urinary tract
            • Same virulence factors
            • P fimbriae - enhances tissue damage
            • α-haemolysin- enhances free iron
            • Cytotoxic necrotizing factor 1 -  enhances tissue damage
          • Endotoxin release
            • lipopolysaccharide parts of the cell wall of gram-negative bacteria - thought to be responsible for the systemic signs of pyometra in bitches
            • Stimulates prostaglandin synthesis (especially PGE₂), which further contributes to the suppressed activity of cellular immunity during diestrus.
              • Measuring  blood concentration of the PGF_2α metabolite (PGFM) also provides an indicator of endotoxin release in bitches with pyometra, and helps in the differentiation between pyometra and CEH
          • Other bacteria
            • Streptococcus spp,
            • Klebsiella species,
            • Staphylococcus aureus,
            • Pasteurella spp,
            • Proteus spp
            • Pseudomonas spp
          • Systemic inflammatory response syndrome (SIRS)
            • Uncontrolled production of other inflammatory mediators
              • tumor necrosis factor (TNF)
              • interleukins (IL-1 and IL-6)
              • platelet activating factor
              •  may provoke irreversible damage to internal organs or septic shock, which can cause death
          • Polyuria/polydypsia
            • Multifactorial origin
            • Renal tubular cell damage,
            • Impaired ability of the loop of Henle to reabsorb sodium and chloride,
            • Increased tubular insensitivity to anti-diuretic hormone (ADH)
            • Loss of urinary concentrating ability.
            •  Not an immunomediated glumerulonephritis.
            • No glomerular damage
            • Reversible after OHE and is most likely due to endotoxin effects

            

            

• May be none with uncomplicated CEH or mucometra or hydrometra
• Usually the dogs are greater than 6 years old, because it takes multiple progesterone exposures. This is a diestrus disease, so estrus was probably within the last month.
• With open cervix pyometra you see a vaginal discharge, lethargy, depression, anorexia/inappetance, polyuria/polydypsia, and vomiting. The dogs are generally relatively healthy though. WBC count is high or normal.
• With closed cervix pyometra you see depression, lethargy, weakness, inappetance, polyuria/polydypsia, and vomiting. The WBC is usually high with a left shift.

Sick

High white count

Polyuria/polydypsis

• History
• Clinical signs
• White blood cell count is usually high (30,000) with a left shift.
• UA
  • May reveal isosthenuria.
  • Do not do cystocentisis
• BUN may be elevated.
• Ultrasound and radiographs show an enlarged, fluid filled uterus. Ultrasound is particularly useful, as the normal pregnant uterus will show up as an enlarged uterus on radiographs.

• Ovariohysterectomy is the treatment of choice in the non-breeding bitch.
  • 5 to 8% mortality
  • Systemic antibiotics for 2 weeks

Lutalyse-the Upjohn-Pharmacia prostaglandin

• Prostaglandin plus antibiotics (broad spectrum to get the E. coli).  If it is a closed cervix pyometra, you should see some discharge by third day of treatment. Some people do not like to treat a closed cervix pyometra with prostaglandins as there is a fear of uterine rupture. There are reports of successful treatments of closed cervix pyometras (some died too!)
  • Relaxing the cervix has been done using Prostaglandin E (misoprostol), applied topically once or twice daily.
  • Administer Lutalyse at a dose of 0.15 mg/kg, SC, BID or TID for 1-1½ days, then 0.25 mg/kg for 5-7 days. You may see all the side effects of prostaglandin such as restless, salivation, urination, vomiting, diarrhea, and cardiovascular collapse. These side effects are reduced if you begin with a low dose and increase the dose second day. The side effects usually diminish as treatment progresses.
  • Reevaluate in 2 weeks. If any signs are still present, repeat the treatment.
• Prostaglandin with a dopamine-agonist or a progesterone-receptor antagonist
  • Clinical improvement in 48 hours
  • No discharge in 4-7 days
  • Normal CBC in 6-15 days
• Dopamine agonists (cabergoline 5 µg/kg once a day or bromocriptine 25 µg/kg, twice or thrice daily) with either natural or synthetic prostaglandins.
  •  Potentiates the luteolytic effects of each drug resulting in a more rapid luteolyses
  • Allows using lower PG doses
  • Progesterone concentrations decline in <24 to 48 hours,
  • Cervical opening  1-2 days,
  • Success rate
    • 80% with the combination of cabergoline (5 µg/kg PO) and cloprostenol (1 µg/kg SC) once a day for 7 days. Cloprostenol administration was continued until day 14, if no response to treatment was observed.
    • 95% - cabergoline (5 µg/kg PO) and cloprostenol (5 µg/kg) administered every third day, during 10 days.
  • Progesterone-receptor antagonists {mifepristone (RU 486) or aglepristone (RU 534)}
    • Competitive antagonists of the progesterone receptor - result in decreased intra-uterine progesterone
    • Prevents progesterone effects
    • Causes cervical relaxation - Aglepristone can be used as an effective means of inducing cervical dilation in cases of closed cervix pyometra (within 48 h)
    • Should be used in combination with prostaglandin
    • Combination of aglepristone (10 mg/kg on days 1, 2 and 8) with cloprostenol (1µg/kg on days 3-7)
      • More effective than aglepristone alone
      • Success rate at day 90 of 84%
      • Clinical signs, blood parameters and uterine diameter consistently improved to normal values,
• Breed the bitch on the next estrus as recurrence likely.
• Fertility (64-87%) has been reported after treatment, however it is lower than normal.