Pathophysiology

Benign prostatic hyperplasia (BPH) is the commonest benign adenoma in the male and develops almost ex clusively in the transitional zone of the prostate gland. The growth and development of the prostate is under the influence of testosterone, specifically its active metabolite dihydrotestosterone (DHT). After conversion by the enzyme 5-a reductase, DHT stimulates androgen receptors in the prostate, which results in the production of growth factors such as epidermal growth factor (EGF). These factors then promote the hyperplasia seen in BPH. It has been postulated that a reduction in apoptosis is also involved in the development of BPH, by causing an imbalance in the ratio of proliferation and apoptosis and hence leading to glandular hy-perplasia. The process also involves an increase in the amount of stromal and smooth muscle tissue of the transitional zone. Histologically, initially small stromal nodules are seen in the transitional zone around the urethra, followed by hyperplasia of the glandular structures. These changes are seen in prostates of men as young as 40, and are increasingly prevalent as the population ages. The size of the gland also tends to increase with age, which is in part responsible for the fact that aging male patients experience an increasing incidence of bladder outflow obstruction (BOO), and although there is no statistically significant link between size of prostate and degree of BOO, there is a correlation between size of prostate and the risk of complications of BPH, including AUR and the need for surgical intervention (Anderson et al. 2001; Chute et al. 1991; Fitzpatrick 2006; Jacobsen et al. 2005; Kirby 2000; Masumori et al. 2003; Thomas et al. 2004).

The smooth muscle of the prostate is under sympathetic nervous control, with synaptic release of norepi-nephrine from nerve terminal granules diffusing across the synaptic gap to stimulate large numbers of aj-adrenoceptors. These are predominantly of the a1A-adrenoceptor subtype, compared with a1B-subtype and a1D-subtype, which are found on blood vessels (causing vasodilatation) and viscera, respectively, and hence antagonists of these receptors are therapeutic targets of interest in the management of BPH. It has been shown that in AUR secondary to BPH, excess a-adrenergic receptor stimulation maybe causative (Caine et al. 1975; Chapple 2001).

Histological BPH tends to progress gradually. Initially, the enlarging transitional zone tissue compresses the surrounding normal prostate tissue, and in time also begins to compress the prostatic urethra. It is this compression that causes a diminishing peak urine flow rate and progressive LUTS. As the caliber of the pros-tatic urethra is reduced by the hyperplastic prostate, it becomes less distensible, and the hyperplastic gland is also less able to relax to allow normal voiding function. Population studies have shown that the prostate increases by an average of 1 - 2 cm3 per year, and in the same series, peak urine flow rates were also seen to diminish by 0.2 ml/s per year. However, individuals show considerable variety, and although in general patients with larger prostate glands tend toward faster rates of growth, the symptoms these patients describe fluctuate greatly. Patients also often find ways of managing their disease so that despite enlarging gland size, their symptoms remain stable (Girman et al. 1999; Roehrborn et al. 2002).

Associated with the increasing obstruction caused by the enlarging prostate, several associated morphological changes in the bladder are commonly seen. The detrusor muscle tends to hypertrophy as a consequence of increasing voiding pressures and associated collage-nous infiltration of smooth muscle, which leads to reduced bladder compliance during filling. In a significant proportion of patients, there is evidence of detru-sor overactivity causing involuntary bladder contractions, although at present it is unclear whether this is directly related to the BOO or is an unrelated age-dependent phenomenon. LUTS therefore seen in patients with BPH causing a degree of BOO (Weiss et al. 2001; Fitzpatrick 2006; Roehrborn et al. 2002; Fong et al. 2005) comprise a combination of storage (frequency, urgency, nocturia) and voiding (hesitancy, intermitten-cy, reduced stream, incomplete emptying) and post-micturition symptoms (postmicturition and terminal dribbling).

With increased age, the problems with bladder emptying tend to progress. Some patients may develop problems fully emptying their bladder, with the development of increased residuals due to an encroaching prostate and worsening obstruction whereby the failing or tiring detrusor is unable to adequately compensate for the obstruction. This can culminate in acute-on-chronic UR, where the patient is unable to void despite a volume often in excess of 1.51 in the bladder. These patients also often have enuresis (so-called overflow incontinence), and in some cases the volumes retained may preclude full recovery of detrusor function (Chapple and Smith 1994). Others may have an episode of AUR, which typically presents as described in Sects. 11.2.2.2 and 11.2.2.4, and requires emergency treatment by catheterization (see Chap. 19, "Surgical Techniques and Percutaneous Procedures"). In some cases, prolonged BOO and the development of residuals will predispose to the formation of bladder stone(s), recurrent urinary tract infections (UTIs; see Sect. 11.2.5.2), and in some cases deterioration of renal function, when the intravesical pressure exceeds the ureteric pressure, hence exerting a back-pressure on the kidneys that can lead to renal failure if left untreated.

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