Cystic Endometrial Hyperplasia/Pyometra Complex

Chapter 23 CYSTIC ENDOMETRIAL HYPERPLASIA/PYOMETRA COMPLEX





PATHOPHYSIOLOGY



Hormonal Influence (Progesterone)









Bacteria


Bacterial contamination of the uterus appears to be a normal phenomenon in the proestrual or estrual bitch, one that is naturally cleared before overgrowth becomes a problem. The most likely bacteria resulting in pathologic uterine infection are those known to inhabit the vaginal vault (Baba et al, 1983). These bacteria have the potential to, and commonly do, ascend through the relatively dilated cervix into the uterus during proestrus and estrus (Noakes et al, 2000). Biochemical fingerprinting of Escherichia coli (E. coli) cultured from the uterus of a bitch with pyometra showed that the organisms were identical or similar to those bacteria isolated from feces of these same dogs (Wadas et al, 1996).


Other bacterial sources for uterine infection have been suggested, including concomitant urinary tract infections and transient bacteremias. However, common vaginal flora is the logical source for uterine contamination. A predominance of E. coli, a common constituent of the normal vaginal flora, is recognized in uterine infections. E. coli may adhere via specific antigenic sites to receptors in the progesterone-stimulated endometrium and myometrium.


The presence of bacterial flora in the vaginal tract is constant. Cervical dilation is associated with proestrus and estrus, and it is assumed that bacterial contamination of the uterus occurs during these phases of the estrous cycle (Baba et al, 1983). However, uterine infection or pathology is rare, suggesting that the inevitable “contamination” is both controlled and rapidly cleared from the normal bitch. Intrauterine bacteria, therefore, cannot solely account for the pathogenesis of pyometra. Significant uterine disease or some other predisposing factor (progesterone or estrogen administration) predisposes bitches to pyometra. Part of the predisposition is the normal postovulation increase in plasma progesterone concentrations, because pyometra is seen only during or immediately following diestrus. Exogenous progesterone administration also increases the incidence of pyometra. Therefore, contributing factors to development of pyometra are CEH, bacteria, diestrus/elevation in serum progesterone concentrations, and exogenous progesterone or estrogen administration.


The bacterium usually associated with pyometra is E. coli. However, staphylococci, streptococci, Klebsiella, Pseudomonas, Proteus, Haemophilus, Pasturella, Serratia, and other bacteria have been isolated from the uteri of bitches with pyometra (Stone, 1985; Wheaton et al, 1989). These bacteria can be identified in the vaginal tracts of healthy normal bitches. The culture results from bitches with pyometra often demonstrate a pure growth of one bacterial species. However, some bitches with pyometra have two or more bacterial isolates cultured from the uterine contents (Memon and Mickelsen, 1993). Normal bitches can have vaginal bacterial flora composed of several bacterial species or a single isolate. It is uncommon for a bitch to have no growth (Bjurstrom and LindeForsberg, 1992).


E. coli is a gram-negative bacterium containing a chemically stable, biologically active lipopolysaccharide endotoxin in the cell membrane. The endotoxin is released as bacteria die and disintegrate. Clinical endotoxemia occurs when serum levels exceed ˜0.05 ng/ml. Clinical signs of endotoxemia include hypothermia, disorientation, and signs of septic shock. The minimum lethal concentration of endotoxin in serum is approximately 0.7 ng/ml. In a review of 92 bitches with pyometra, 7 had endotoxemia. Furthermore, the release of endotoxin may be enhanced and clinical signs exacerbated by antibiotic treatment, since antibiotics should increase the rate at which bacteria die (Frannson et al, 1997; Johnston et al, 2001).



Estrogen


Exogenous estrogen, regardless of the specific chemical form used, enhances the stimulatory effect of progesterone on the uterus. This appears to be the result of estrogen sensitizing progesterone receptors and enhancing the binding of progesterone (Niskanen and Thrusfield, 1998). Supraphysiologic concentrations of estrogen resulting from exogenous administration (e.g., mismate injections) during estrus or diestrus dramatically increase the risk for developing pyometra. For this reason, estrogen injections to prevent pregnancy are strongly discouraged.




SIGNALMENT AND HISTORY







CLINICAL PATHOLOGY



White Blood Cell Counts


The total white blood cell count in bitches with pyometra is variable. An absolute neutrophilia (usually <25,000 cells/μl) with variable degrees of cellular immaturity (presence of a “left shift,” that is, <300 bands/μl) may be observed secondary to significant infection, inflammation, and septicemia. The infection, if severe and/or chronic, may cause a “degenerative left shift” with toxic neutrophils. Although increases in total white blood cell counts are identified in a slight majority of bitches with open-cervix pyometra (50% to 75%), normal or even decreased white blood cell counts may be documented. Some of these dogs do not exhibit evidence of the overwhelming infection seen in closed-cervix pyometra. Seventy-eight of the 163 (48%) bitches with open-cervix pyometra we have treated with PGF had total white blood cell counts within the normal range before initiation of any therapy. Of those managed surgically, 20 of 80 (25%) had total white blood cell counts within the normal range (Wheaton et al, 1989).


The percentage of bitches with increased white blood cell counts that have closed-cervix pyometra is greater than those with increased white blood cell counts and open-cervix pyometra. Also, the percentage of bitches with abnormally decreased white blood cell counts and closed-cervix pyometra is greater than with open-cervix pyometra. In 42 closed-cervix pyometra dogs treated with prostaglandins at our clinic, 36 (86%) had abnormally increased white blood cell counts and 5 (12%) had decreased counts (<5000/μl).





Urinalysis and Urine Culture


The urine specific gravity is unpredictable in bitches with pyometra because of the many variables that can affect the results. Early in the disease process, the urine specific gravity may be greater than 1.030 simply as a reflection of dehydration and the physiologic response to conserve fluids. With secondary bacterial infection, especially E. coli, toxemia develops and interferes with the resorption of sodium and chloride in the loop of Henle. This reduces renal medullary hypertonicity, impairing the ability of the renal collecting tubules to resorb free water. Polyuria and compensatory polydipsia result.


A renal tubular insensitivity to the action of antidiuretic hormone (ADH) can result in secondary nephrogenic diabetes insipidus. This represents a sequela to reversible renal tubular damage caused by E. coli endotoxins. This development may also contribute to a loss of concentrating ability. Renal tubular immune complex injury is another proposed mechanism for polydipsia/polyuria. Although not likely, prolonged polyuria and polydipsia may cause renal medullary solute washout, further impairing the kidney’s ability to conserve water. Probably as a result of the reversible renal secondary diabetes insipidus, urine becomes progressively more dilute. Isosthenuria (urine specific gravity 1.008 to 1.015) or hyposthenuria (urine specific gravity <1.008) is well recognized in bitches with pyometra. Prerenal uremia may also be present if water consumption inadequately compensates for the polyuria.


Urinary tract infections may be suspected if pyuria, hematuria, and/or proteinuria are identified on urinalysis. However, urine obtained by a midstream collection is contaminated by the vaginal discharge. We do not recommend “blind” cystocentesis techniques on dogs with suspected or known pyometra because of the risk for puncturing an infected uterus and subsequent leakage of its contents into the abdomen. Cystocentesis using ultrasound guidance reduces the risk for penetrating the uterus. If an uncontaminated urine sample is considered important, it should be obtained only with ultrasound guidance. If ultrasonography is not available, one should not routinely culture the urine of dogs with pyometra.


Proteinuria without pyuria or hematuria may also be found with pyometra. Immune complex deposition in the glomeruli causes a mixed membranoproliferative glomerulonephropathy and leakage of plasma proteins into the glomerular filtrate. The proteinuria gradually resolves with correction of the pyometra.

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Jul 10, 2016 | Posted by in INTERNAL MEDICINE | Comments Off on Cystic Endometrial Hyperplasia/Pyometra Complex
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