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1 Prostate Day 2006 Aging Bladder and LUTS 충남대학교의과대학비뇨기과학교실 김홍식 서 하부요로증상은연령이많아질수록그빈도가증가하며, 노년기남성의삶의질을악화시키는대표적증상이다. 과거의관점에서이러한남성하부요로증상의증가는전립선의비대나종양의발생에의한것으로여겨져왔으며, 이러한전립선질환의치료를통해하부요로증상을개선하고자노력해왔다. 그러나압력요속검사를통한연구에서노년기하부요로증상의약 1/3 정도는방광하부폐색과연관이없는것으로알려지고있으며, 1,2) 또한 60세이상의남성에서폐색증상의여부와배뇨압은상관이없는것으로보고되고, 무증상남성 47% 가압력요류검사에서폐색의소견을보이는것으로알려져있다. 3) 이러한연구결과는노년기하부요로증상의치료목표를방광출구폐색의해소만으로할경우완전한치료가어려울수있음을보이며, 폐색증상만을주소로전립선절제술을시행한환자중 25% 에서적절한치료결과를얻지못하는이유를알려주고있다. 4,5) 더하여 TURP로치료한전립선비대증을장기추적한결과, 초기에좋은결과를얻은환자들이증상의악화와요속의감소를호소할때상당수의환자가폐색의재발보다는배뇨근저반사에의한증상악화인것으로나타나고있다. 6) 또한동일연령대의남성과여성의하부요로증상을증상점수를이용하여비교할때, 유사한정도의증상을나타내는결과를얻고있다. 7) 이러한결과는하부요로증상이방광출구폐색과큰연관이없을경우도있을가능성을시사한다. 따라서하부요로증상의완전한이해와치료를위해서는방광출구와함께배뇨과정의큰축을담당하는방광이연령의증가에따라어떠한변화를보이며, 이러한변화가하부요로증상에어떠한영향을미치는지에관하여알아야할필요가있다. 이러한연령의증가와하부요로증상의관계에관하여충분히고찰한후에야하부요로증상의적절한치료가이루어질수있을것이다. 본 1. 전립선의변화가방광에미치는영향남성에서전립선의크기증가및요도내압증가는방광출구폐색을유발하여노년기하부요로증상의중요한원인이된다. 이러한방광출구폐색은그자체로요속을저하시키고배뇨증상을유발하게되지만, 폐색자체뿐아니라그에따라유발되는방광의변화도증상변화에중요한역할을하게된다. 높은압력으로방광이충만되거나출구폐색을이기기위해방광배뇨근의수축압이증가하게되면방광벽은현저한허혈성변 62

2 김홍식 :Aging Bladder and LUTS 화가일어나게되고순응도감소와배뇨근과반사, 수축력저하등의변화가수반되게된다. 8,9) 이러한변화를구조적인면에서살펴보면, 먼저방광무게가증가됨을알수있다. 방광평활근의비대가진행되면세포의형태가변화되게되고큰크기에도불구하고효과적인수축은일어날수없게된다. 또한각세포사이에콜라겐이침착되면서적절한신경전달도방해받게된다. 10) 여기에방광의수축을조절하는콜린성신경의퇴화도관찰되며신경밀도의감소는적절한배뇨가어렵게하는경향을보인다. 더하여미토콘드리아내의산화대사작용도감소되어배뇨근수축을저하시키고배뇨능력을감소시키게된다. 11,12) 2. 혈관계의변화가방광에미치는영향혈관계의연령에따른변화가배뇨근의기능에어떠한영향을미치는가하는것은아직잘알려져있지않다. 그러나, 심혈관계질환과요실금의상관관계는보고되고있다. 13) 또한혈관계질환의위험인자인흡연과남성의하부요로증상이연관이있다는보고도있다. 14) 이러한연관의원인은명확하지는않지만혈관의죽상경화변화에의한배뇨근의허혈성변화와연관이있을것으로추정되고있다. 이러한추정을입증하기위해방광의허혈성변화를유발한쥐의방광에서순응도감소및과활동성, 수축반응감소의소견이관찰되었으며, 혈류가개선된후에는이러한변화가호전됨이관찰되었다. 15) 3. 신경계의변화가방광에미치는영향방광과전립선에의한배뇨기능은모두신경의지배를받는다. 당연히신경계에이상이발생하는경우배뇨기능의변화가오게된다. 이러한신경계의질환중연령의증가에의해늘어나는대표적인질환에는당뇨, 파킨슨씨병, 뇌졸중, 치매, normal pressure hydrocephalus 등이있다. 1) 당뇨당뇨병성방광병증이대표적으로장기간의고혈당증의결과신경계전반에 axonal damage가오게되고 demyelination이발생하게된다. 이로인해방광기능에이상이발생하여방광감각이저하되고배뇨간격이늘어나며배뇨근의수축이줄어들고잔뇨가증가하여요폐에이르게된다. 16) 182명의당뇨환자를대상으로시행한요역동학검사에서는배뇨근과반사 55%, 배뇨압감소 23%, 배뇨근무반사 10% 의소견을보였고, 36% 의남성에서방광출구폐색이동반되었다. 2) 파킨슨씨병이질환이있는환자의하부요로증상빈도는노화나기타다른질환들의병발에의한영향을배제하기어렵다는이유때문에논란이많은부분이다. 그러나일반적으로 substantia nigra에서 pontine micturition center로가는억제신호의이상에의한배뇨근과반사가많은것으로알려져있으며괄약근의 sphincter bradykinesia 가나타나지만배뇨근과협조운동은가능한것으로알려져있다. 이러한배뇨근과반사는급박성요실금을유발할수있고, 항콜린제에의해증상이개선되지만괄약근기능이상등에의해요폐가일어날위험도항시고려되어야한다. 17,18) 3) 뇌졸중뇌졸중에의해유발되는요실금의원인으로세가지를들수있다. 첫번째는신경배뇨조절중추의손상에의한방광의배뇨근과반사와그로인한급박성요실금이고, 두번째는인지기능과언어기능등의손상에의한것으로배뇨기능자체에는이상이없는경우이고, 세번째는동반된신경장애혹은약물투여로인한배뇨근저반사및일류성요실금의유발등이다. 19) 그러나, 이러한변화는뇌졸중발생전부터존재할수있 63

3 Prostate Day 2006 는하부요로증상에의해변화될수있으므로치료에주의를요하게된다. 또한요실금의여부는환자의예후와밀접한연관을가지게되므로뇌졸중후발생한하부요로증상에더욱주의가필요하다. 20) 4) 치매치매환자에있어서요실금은 22~90% 까지넓게보고되고있다. 대체적으로질환의심한정도에따라증가되는것으로알려지고있다. 이러한요실금은인지장애의정도, 행동지연, 구속여부, 동반질환과약물등에영향을받는다. 21) 요실금의발생원인은대뇌기능저하에의한억제기능의소실로생각되고있으며, 배뇨근과반사가문제가된다고보고있으나, 요역동학검사로완전히입증되지는않았다. 치매환자는방광기능조절을위한행동치료가어렵고, 항콜린제는치매증상을심하게할수있어치료에어려움이따르지만배뇨시간조절과착탈이쉬운옷을착용시키고화장실에접근성을개선하면증상의호전을많이기대할수있는것으로알려지고있다. 22) 4. 방광배뇨근및기능자체의변화방광의조직학적변화를관찰한결과, 방광평활근과결합조직의비율이방광출구폐색의여부와관계없이남성과여성모두에서연령의증가에따라감소함이관찰되었다. 23,24) 또한다른연구에서방광결합조직의밀도가작은혈관들의동맥경화성변화와함께연령의증가와비례하여증가됨이관찰되었다. 25) 기능적인변화도관찰되었는데, 40세이상의남녀 436명의연구에서최대요속의감소, 배뇨량과방광용적의감소, 잔뇨량의증가가나타났고, 80세이후에방광순응도도현저하게감소하는것이관찰되었다. 26,27) 이러한연령에따른요역동학적변화는배뇨증상이없는남성에게도발견되었는데, 50~92세의무증상남성을대상으로한연구에서최대요속과배뇨량이현저하게감소함이발견되었다. 28) 연령의증가에따라배뇨근압과최대요속의감소가나타남과함께구조적인변화도관찰되고있는데, 콜라겐과엘라스틴이배뇨근세포에참착되고이는다른원인에의한배뇨근기능이상에의해더욱촉진되는양상을보이게된다. 폐색이없는안정적인방광의경우에도 dense band의길이가길어지고 acetylcholinesterase-positive nerve의감소가관찰되어이러한변화와연관된것으로추정되고있다. 29) 5. 기타노년기에호발하는질환이방광에미치는영향배뇨근저반사를일으키는질환에는여러가지가있는데, 당뇨, 갑상선기능저하증, 신부전에의한요독증과같은대사성질환과 Guillain-Barre syndrome, tabes dorsalis 같은감염성질환, paraneoplastic-syndrome, 결체조직질환과같은전신성질환들이있다. 결 전립선비대에의한방광출구폐색은남성에서하부요로증상을유발하는가장큰원인임에틀림없다. 그러나이러한전립선비대증자체의영향혹은연령의증가에따른신경계, 혈관계의변화와여러가지퇴행성, 대사성, 신경성질환등의영향이단독혹은복합적으로방광에일으키는변화는이러한하부요로증상에큰영향을미치게된다. 따라서전립선질환에대한이해와함께연령증가에따른방광의변화에대하여고찰하는것이남성의하부요로증상을적절히치료하는데중요하게작용될것으로생각된다. 64

4 김홍식 :Aging Bladder and LUTS 참고문헌 1. Poulsen AL, Schou J, Puggaard L, Torp Pedersen S, Nordling J. Prostatic enlargement, symptomatology and pressure/ flow evaluation: interrelations in patients with symptomatic BPH. Scand J Urol Nephrol 1994;157: Rollema HJ, Mastrigt RV. Improved indication and follow up in transurethral resection of the prostate using the computer program CLIM. A prospective study. J Urol 1992;148: Diokno AC, Brown MB, Goldstein NG, Herzog AR. Urinary flow rates and voiding pressures in elderly men living in a community. J Urol 1994;151: Yalla SV, Sullivan MP, Lecamwasam H, DuBeau CE, Vickers MA, Cravalho EG. Correlation of American Urological Association symptom index with obstructive and nonobstructive prostatism. J Urol 1995;153: Holtgrewe HL. Transurethral prostatectomy. Urol Clin North Am 1995;22: Thomas AT, Cannon A, Bartlett E, Ellis Jones J, Abrams P. The natural history of lower urinary tract dysfunction in men: Minimum 10 year urodynamic followup of transurethral resection of prostate for bladder outlet obstruction. J Urol 2005;174: Lepor H, Machi G. Comparison of AUA symptom index in unselected males and females between fifty five and seventy nine years of age. Urology 1993;42: Azadzoi KM, Pontari M, Vlachiotis J, Siroky MB. Canine bladder blood flow and oxygenation: Changes induced by filling, contraction and outlet obstruction. J Urol 1996;155: Chen MW, Buttyan R, Levin RM. Genetic and cellular response to unilateral ischemia of the rabbit urinary bladder. J Urol 1996;155: Meyer S, Elbadawi A. Morphometry of the obstructed detrusor: II. Principles of a comprehensive protocol. Neurourol Urodynam 1989;8: Speakman MJ, Brading AF, Gilpin CJ, Dixon JS, Gilpin SA, Gosling JA. Bladder outflow obstruction a cause of denervation supersensitivity. J Urol 1987;138: Zhao Y, Wein AJ, Bilgen A, Levin RM. Effect of anoxia on in vitro bladder function. Pharmacology 1992;43: Diokno AC, Brock BM, Herzog AR, Bromberg J. Medical correlates of urinary incontinence in the elderly. Urology 1990;36: Koskimaki J, Hakama M, Huhtala H, Tammela TL. Association of smoking with lower urinary tract symptoms. J Urol 1998;36: Gill HS, Monson FC, Wein AJ, Ruggieri MR, Levin RM. The effects of short term in vivo ischemia on the contractile function of the rabbit urinary bladder. J Urol 1988;139: DuBeau CE. Interpreting the effect of common medical conditions on voiding dysfunction in the elderly. Urol Clin North Am 1996;23: Berger Y, Blavais JG, DeLRoche ER, Salinas JM. Urodynamic findings in Parkinson s disease. J Urol 1987;138: Eitzmaurice H, Fowler CJ, Rickards D. Micturition disturbances in Parkinson s disease. Br J Urol 1985;57: Gelber DA, Good DC, Layven LJ, Verhulst SJ. Causes of urinary incontinence after acute hemispheric stroke. Stroke 1993;24: Nakayama H, Jorgensen HS, Pedersen PM, Raaschou HO, Olsen TS. Prevalence and risk factors of incontinence after stroke. The Copenhagen Stroke Study. Stroke 1997;28: Skelly J, Flint AJ. Urinary incontinence associated with dementia. J Am Ger Soc 1995;43: Evans SN, Castleden CM. Neurological disorders in the ageing population and their urological implications. Br J Urol 1998;82(Suppl 1): Lepor H, Sunaryadi I, Hartanto V, Shapiro E. Quantitative morphometry of the adult human bladder. J Urol 1992; 148: Holm NR, Horn T, Hald T. Detrusor in aging and obstruction. Scand J Urol Nephrol 1995;29: Cannon E, Timmermans LG, Reznik M, Timmermans LM. Ultrastructural modifications of the bladder wall in senescence. Acta Urol Belg 1990;58: Madersbacher S, Pycha A, Schatzi G, Mian C, Klingler CH, Marberger M. The aging lower urinary tract: A compa- 65

5 Prostate Day 2006 rative urodynamic study of men and woman. Urology 1998;51: Ameda K, Koyanagi T, Nantani M, Taniguchi K, Matsuno T. The prevalence of preoperative cystometrography in patients with benign prostatic hyperplasia: correlating the findings with clinical features and outcome after prostatectomy. J Urol 1994;152: Jorgensen JB, Jensen KM E, Bille Brahe NE, Mogensen P. Uroflowmetry in asymptomatic elderly males. Br J Urol 1986;58: Elbadawi A, Yalla SV, Resnick NM. Structural basis of geriatric voiding dysfunction. Ⅱ. Aging detrusor: normal versus impaired contractility. J Urol 1993;150:

슬라이드 1

슬라이드 1 Proposed Korean guideline for the diagnosis of BPH Hyun Woo Kim The Catholic University of Korea BPH Guideline AHCPR guideline on BPH (1994) AUA guideline on BPH (2003) EAU guideline on BPH (2004) International