Prostatitis Syndromes. Part 2: Pathogenesis
Bacterial. An understanding of the etiology and pathogenesis of prostatitis is essential in the investigation and treatment of these syndromes. The bacteria causing both acute and chronic bacterial prostatitis are similar in type and incidence to those that cause simple urinary tract infections (UTIs). As in cystitis, Gram-negative bacteria are the most common, with Escherichia coli predominating. Gram-positive bacteria, such as enterococci, can also be implicated in this disease. Whether other Gram-positive bacteria, such as coagulase-negative staphylococci, streptococci, and diptheroids, are implicated is controversial. However, a number of investigators, including my own group, have found Gram-positive bacteria in significant numbers in the prostatic secretion and have further confirmed this by culturing prostatic biopsy specimens. Thus I believe that these bacteria are occasionally implicated in chronic inflammation of the prostate gland. The bacteria can enter the prostate gland by a number of routes. Although the hematogenous and lymphatic routes of bacterial spread are theoretically possible, they must be very rare. Experimental work in our laboratory and clinical data collected over the last decade suggests that intraductal reflux from the urethra is the most common route of infection. It has been ascertained that patients with prostatic inflammation do have intraprostatic reflux of urine during voiding. We have substantiated this with voiding cystourethrograms, particularly in refractory cases. Carbon particles instilled in the bladder can be found on prostatic specimens after prostate gland resection. The bacteria enter the prostate gland from infected urine or urethritis. This is particularly important in catheterized patients, in whom bacteria adhere to the outside surface of the catheter and are able to enter the prostate gland very easily in susceptible patients.
Once the bacteria enter the ducts and acini of the prostate gland, they multiply within the ductal system. Acute inflammation results, with infiltration of acute inflammatory cells into the ducts. The ducts become engorged with acute inflammatory infiltrate made up of dead and live bacteria as well as living and dying polymorphonuclear leukocytes. At this point the entire gland is acutely inflamed, and the bacterial presence within the prostate and urine is easily demonstrated. With acute host defense mechanisms and antibiotics, the bacteria eventually clear, and the prostatic inflammation resolves with no residual damage to the gland.
If some of the bacteria persist, either from subacute inflammation or an acute prostatitis, they form small sporadic microcolonies within the ductal system adherent to the epithelium. Bacteria produce an exopolysaccharide slime or glycocalyx that envelops these microcolonies and, when combined with a slowed metabolic respiratory rate within the prostatic environment, makes them almost immune to host defenses and antibiotics. In this state, however, the outer exopolysaccharide shell exerts an extremely immunogenic influence. Local and systemic immune systems are mobilized, resulting in chronic lymphocytic infiltrate within the interstitium and ductal system with final fibrosis of the interstitium and obliteration of the ductal system in focal areas.
The bacteria become quiescent during antibiotic therapy, but once antibiotic therapy is discontinued, they become evident again. They begin to multiply and cause an acute on chronic inflammatory reaction, exacerbating chronic prostatitis. Each time this happens it becomes more difficult to eradicate the bacteria because of the irreversible inflammatory damage sustained by the prostate gland. Bacteria can be noted on scanning electron micro-graphic studies of prostate biopsies in patients with chronic bacterial prostatitis who have been on continuous antibiotic therapy for years (Figure 1).
Non-bacterial. Perhaps the greatest number of cases of prostatitis have no known cause, despite chronic inflammation. These are assumed to be non-bacterial. While Gram-positive bacteria other than enterococci can be found in prostatic secretions, many researchers exclude them as a possible cause and explain their presence by urethral contamination. Other clinicians, however, including my own research group, are now considering these agents as possible causes of chronic bacterial prostatitis. Several non-bacterial agents are presumed to cause prostatitis, including ureoplasma or mycoplasma and chlamydia, but no reported studies conclusively confirm these organisms.
Intraprostatic reflux of sterile urine has also been hypothesized in the pathogenesis of non-bacterial prostatic inflammation.” My current research in patients with chronic prostatitis refractory to antibiotic therapy leads me to believe that many have had chronic bacterial prostatitis in the past and that the bacteria or bacterial antigens remain in the prostate gland, although they are difficult to demonstrate on standard culture techniques. Further immunologic studies are needed to distinguish bacterial from non-bacterial prostatitis clearly.
Prostatodynia. Patients with prostatodynia have no history of a documented UTI. No infectious agent can be located in quantitative cultures, and there is no inflammatory response in the prostatic secretions. Urodynamic evaluation can disclose an abnormality of the pelvic sympathetic nervous system with incomplete relaxation of the bladder neck and urethral sphincter.