Bladder outlet obstruction

Regulation of prostate growth and development of benign prostatic hyperplasia (BPH) 64

Pathophysiology and causes of bladder outlet obstruction (BOO) and BPH 66

Benign prostatic obstruction (BPO): symptoms and signs 68

Diagnostic tests in men with LUTS thought to be due to BPH 70

Why do men seek treatment for their symptoms? 72 Watchful waiting for uncomplicated BPH 74

Medical management of BPH: A-blockers 76

Medical management of BPH: 5A-reductase inhibitors 78 Medical management of BPH: combination therapy 80 Medical management of BPH: alternative drug therapy 82 Minimally invasive management of BPH: surgical

alternatives to TURP 84

Invasive surgical alternatives to TURP 86 TURP and open prostatectomy 88

Acute urinary retention: definition, pathophysiology, and causes 90

Acute urinary retention: initial and definitive management 94

Indications for and technique of urethral catheterization 96

Indications for and technique of suprapubic catheterization 98

Management of nocturia and nocturnal polyuria 100 High-pressure chronic retention (HPCR) 102

Bladder outlet obstruction and retention in women 104 Urethral stricture disease 106

64 CHAPTER 3 Bladder outlet obstruction

Regulation of prostate growth and development of benign prostatic hyperplasia (BPH)

BPH is characterized by an increase in epithelial and stromal cell numbers (hyperplasia) in the periurethral area of the prostate. New epithelial gland formation is normally only seen during fetal development. The development of new glands in the adult prostate has given rise to the concept of ‘reawakening’ of the inductive effect of the prostatic stroma on the prostatic epithelium.

The increase in prostate cell number could reflect proliferation of epithelial and stromal cells, impairment of programmed cell death, or a combination of both. During the early phases of development of BPH, cell proliferation occurs rapidly. In established BPH, cell proliferation slows down and there is impairment of programmed cell death (androgens and estrogens actively inhibit cell death).

The role of androgens in BPH (Fig. 3.1)

Testosterone can bind directly to the androgen receptor, or may be converted to a more potent form, dihydrotestosterone (DHT), by the enzyme 5α-reductase (5AR).

There are two isoforms of 5AR: type I, or extraprostatic, 5AR (which is absent in prostatic tissue and present in, for example, skin and liver) and type II, or prostatic, 5AR (which is found exclusively on the nuclear membrane of stromal cells, but not within prostatic epithelial cells). Type I 5AR is not inhibited by finasteride, whereas type II 5AR is. Dutesteride will block both type I and type II 5AR isoforms.

Testosterone diffuses into prostate and stromal epithelial cells. Within epithelial cells it binds directly to the androgen receptor. In prostate stromal cells a small proportion binds directly to the androgen receptor, but the majority binds to 5AR (type II) on the nuclear membrane, is converted to DHT, and then binds (with greater affinity and therefore greater potency than testosterone) to the androgen receptor in the stromal cell.

Some of the DHT formed in the stromal cells diffuses out of these cells and into nearby epithelial cells (a paracrine action). The androgen receptor–testosterone or androgen receptor–DHT complex then binds to specific binding sites in the nucleus, thereby inducing transcription of androgen-dependent genes and subsequent protein synthesis.

It is thought that stromal–epithelial interactions may be mediated by soluble growth factors—small peptides that stimulate or inhibit cell division and differentiation. Growth stimulating factors include basic fibroblastic growth factor (bFGF), epidermal growth factor (EGF), keratinocyte growth factor (KGF), and insulin-like growth factor (IGF).

Transforming growth factors (e.g., TGF-B) normally inhibit epithelial cell proliferation, and it is possible that in BPH, TGF-Bis down-regulated.

DHT produced peripherally by Type 1 & Type 2 5 -Reductase

Figure 3.1 Testosterone (T) diffuses into the prostate epithelial and stromal cell (see text). This figure was published in Walsh PC, et al. Campbell’s Urology,

8th edition, p. 1299. Copyright Elsevier 2002.

66 CHAPTER 3 Bladder outlet obstruction

Pathophysiology and causes of bladder outlet obstruction (BOO) and BPH

The principle cause of BOO in men is BPH. Less common causes are urethral stricture and malignant enlargement of the prostate.

BOO in women is altogether less common, the causes including pelvic prolapse (cystocele, rectocele, uterine), the prolapsing organ directly compressing the urethra; urethral stricture; urethral diverticulum; post-surgery for stress incontinence; Fowler syndrome (impaired relaxation of external sphincter occurring in premenopausal women, often in association with polycystic ovaries); and pelvic masses (e.g., ovarian masses).

In either sex, neurological disease (spinal cord injury, spina bifida, multiple sclerosis [MS]) can cause failure of relaxation of the external sphincter during voiding (detrusor sphincter dyssynergia [DSD]).

The pathophysiological basis of BOO due to benign prostatic enlargement (BPE) secondary to BPH (benign prostatic obstruction, BPO) has been studied more than any other type of obstruction. BPO has dynamic and static components:

•Dynamic component of BPO: A1-adrenoceptor-mediated prostatic smooth muscle contraction. Smooth muscle accounts for approximately 40% of the area density of the hyperplastic prostate and human prostate contracts following administration of A-adrenergic agonists. This effect is the rationale for A-adrenoceptor blocker treatment for symptomatic BPO.

•Static component of BPO: mediated by the volume effect of BPE.

Pathophysiological consequences of BOO

John Hunter (1786), who founded the Royal College of Surgeons of England, noted that “the disease of the bladder arising from obstruction alone is increased irritability and its consequences, by which it admits of little distension, becomes quick in its action and thick and strong in its coats.”

BOO causes thickening of the wall of the bladder. Microscopically, smooth muscle cells enlarge and there is an increase in connective tissue (collagen and elastin) between the smooth muscle bundles. In some cases, this may lead to poor compliance, with development of high bladder and intrarenal pressures. Progressive hydronephrosis can develop, with impairment of renal function and even renal failure (high-pressure chronic urinary retention).

Experimentally created BOO causes development of bladder overactivity (unstable bladder contractions during bladder filling). This may be due to prolonged increased intravesical pressure during voiding causing ischemia and leading to ischemic damage to neurons within the bladder (i.e., denervation).

Symptomatically, many patients with BOO develop frequency, urgency, and urge incontinence.

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