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1、The Prostate and Benign Prostatic Hyperplasia,Accessory Sex Glands,Prostate Seminal vesicles Cowpers glands,We Will Consider,The structure of the prostate and its role in continence The mechanism of ejaculation and the role of the prostatic innervation The role of the secretory products of the prost
2、ate in the prostatic fluid,The Structure of the Prostate,McNeals Hypothesis Transitional zone the site of origin of BPH Central zone Wolffian duct origin cf vasa and seminal vesicles Peripheral zone the site of origin of 75% of cancers Anterior fibromuscular stroma,Origin,Peripheral and central zone
3、s - UG sinus DHT Central zone Wolffian ducts Testosterone,Origin of Circulating Testosterone,Testosterone Uptake,Development of the Prostate,DHT formed mainly in epithelial cells DHT diffuses to stroma (most of the androgen receptors) Stromal nuclei produce growth factors Growth factors drive epithe
4、lial cells Stromal epithelial interaction,Summary,Growth Factors,Normally bFGF EGF TGF 20% TGF inhibitory,80%,stimulatory,The Pre-prostatic Sphincter,Prostatic Innervation,Classical adrenergic cholinergic,NANC 5-HT Dopamine-hydroxylase VIP NPY Leu-encephalin Met-encephalin CGRP Sustance P,Alpha Adre
5、nergic Innervation,-adrenergic receptors 98% in stroma alpha-1 90% alpha-2 10% alpha 1a 60%,Innervation,Cholinergic - epithelial secretion Adrenergic - smooth muscle contraction Neuroendocrine cells - serotonin calcitonin TSH somatostatin - regulation of secretion, cell growth NANC - ?,Bladder Neck
6、v Preprostatic Sphincter,Bladder Neck Both sexes At bladder neck Cholinergic innervation Continence mechanism,Preprostatic sphincter Males Supraverumontanal Adrenergic innervation Genital sphincter,Ejaculation - Mechanism,Spermatozoa and prostatic fluid, then seminal vesicle fluid = Emission Antegra
7、de despite competent urethral mechanism Voiding difficult with an erection and immediately after ejaculation,Bladder Neck Tightens U/S,Urethral Pressure Profile,Ejaculation Sequence,Bladder neck tightens Emission of vasal ampullary sperm Contraction of bulbospongiosus Contraction of prostatic smooth
8、 muscle Urethral sphincter mechanism overcome Further contraction of prostate and seminal vesicle contraction,Seminal Plasma,2ml seminal vesicle secretion 0.5ml prostatic secretion 0.1ml Cowper,s glands and glands of Littr,Role of Seminal Plasma,Optimise fertilisation (ejaculated sperm v aspirated s
9、perm) protective effect enhance motility and survival directly Protective effect on urinary tract biological esp. Zn, spermine, Ig mechanical washing Lubrication,Prostatic Secretion,Proteins Acid phosphatase PSA Leucine aminopeptidase Diamine oxidase Glucuronidase Plasminogen activator Complement C3
10、 and C4 Transferrin, transferritin Growth factors Annexin 1,Non proteins Citrate Spermine Spermidine Putrescine Zinc Myoinositol Cholesterol,Functions,Zinc - 4 structure of sperm chromatin PSA semen liquefaction Otherwise?,Non-Proteins,Citrate 240-1300 times concentration elsewhere Zinc Polyamines E
11、xist as a complex to maintain electrochemical neutrality,also in uniquely high concentrations,Benign Prostatic Hyperplasia,BPH - Misconceptions,Generalised disease of the prostate due to hormonal derangement which leads to enlargement of the gland which causes compression of the urethra leading to s
12、ymptoms,Aetiology,Age Functioning testes Prostate normal to begin with Possibly a series of genetic hits which, with further hits, will lead to cancer,Other Factors,Racial - american blacks v orientals Dietary - yellow vegetables, western diet,Pathogenesis,Androgens - permissive Stromal epithelial i
13、nteraction normal 2:1, BPH 3 or 4:1 major change is connective tissue,Stromal-Epithelial Ratio in BPH,Epithelium 25%+/- Stroma 75%+/- - connective tissue 50%+/- - smooth muscle 25%+/-,Pathogenesis - 2,Micronodules: transition zone laterally micronodules in periurethral zone posteriorly,Pathogenesis
14、- 3,Transition zone enlarges laterally on each side stroma and epithelium Periurethral zone enlarges posteriorly stroma only firoblasts transforming to smooth muscle cells embryonic reawakening,Histology,Posterior,Lateral,Androgens and BPH,Permissive in vivo and in vitro Growth factors are just as i
15、mportant,Growth Factors and the Prostate,Normal bFGF EGF stimulatory TGF TGF - inhibitory,Growth Factors and the Prostate,BPH bFGF stromal autocrine stimulatory KGF stromal paracrine stimulatory TGF1 stromal autocrine/paracrine inhibitory TGF2 epithelial autocrine/paracrine inhibitory IGF stromal pa
16、racrine stimulatory,Growth Factors and the Prostate,?TGF upregulated by declining serum testosterone which then secondarily affects other growth factors ?lifelong ejaculation/voiding affecting the bend,Ageing,BPH Detrusor instability Impaired detrusor contractile efficiency,Symptomatic BPH,BPH alone
17、 BPH plus detrusor instability BPH plus impaired detrusor contractility BPH plus DI plus IDC IDC without BPH in the elderly IDC plus DI without BPH in the elderly,Urodynamic Aspects of BPH,age related decline in urinary flow rate age related increase in detrusor instability outflow obstruction,Outflow Obstruction,Obstruction is a pressure-flow phenomenon Pressure is the primary determinant,Questions,What are the symptoms of BPH alone? How does BPH cause obstruction? Does the obstructed bladder decompensate? What is the cause of acute retention?,