Cho KJ Kim JC Pathophysiology of LUTD in the elderly 하부요로의해부학적변화 노화는피부와점막의점진적위축, 골격근부피의감소, 평활근긴장도의저하, 신경계의변성을일으키며, 이런모든것들이하부요로기능에잠재적으로부정적영향을줄수있다. 하부요로

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1 FOCUSED ISSUE OF THIS MONTH J Korean Med Assoc 2015 October; 58(10): pissn / eissn 노인의하부요로기능변화와배뇨장애기전 조강준 김준철 가톨릭대학교의과대학부천성모병원비뇨기과 Pathophysiology of lower urinary tract dysfunction in the older patient Kang Jun Cho, MD Joon Chul Kim, MD Department of Urology, Bucheon St. Mary s Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea Understanding the pathophysiology of lower urinary tract dysfunction in the elderly is necessary for the adequate management of lower urinary tract dysfunction, as aging causes anatomical and functional changes in the lower urinary tract. While epithelium atrophy of genitourinary organs and detrusor muscle changes occur in elderly women, due to estrogen decline, prostate enlargement may lead to bladder outlet obstruction and wall thickening in elderly men. Urodynamic changes that occur with aging include bladder outlet obstruction, detrusor overactivity and underactivity, decreased bladder compliance, and detrusor hyperactivity with impaired contractility. Moreover, impaired mobility, central nervous system diseases, non-genitourinary comorbidities, and various medications can also influence lower urinary tract function. Among these age-associated multifactorial conditions, adequate differentiation and management of the factors responsible for lower urinary tract dysfunction is of paramount importance in elderly patients. Key Words: Aging; Lower urinary tract symptoms; Physiopathology; Urinary incontinence 서론 면, 방광을포함한하부요로는일생동안약 15 만번정도 의배뇨를하게된다. 결국노화로인한하부요로의변화는 하부요로는방광과요도, 그리고남성의전립선으로구성되어있으며, 주요기능은소변의저장과배출이다. 저장기능에이상이생길경우빈뇨, 야간뇨, 요절박, 요실금등의증상이나타나며, 배출기능에이상이생길경우약뇨, 요주저, 복압배뇨, 잔뇨감, 요폐등의증상으로나타난다. 1일 6회정도배뇨를하는것으로가정하고 70세를기준으로한다 피할수없는현상이며, 노인에서발생하기쉬운다른질환및원인이하부요로에영향을줄수있는점까지고려한다면, 노인은하부요로기능변화와이로인한배뇨장애에취약할수밖에없다. 실제로 2006년한국에서 18세이상의성인 2,000명을대상으로시행한조사에따르면, 전체하부요로증상의유병률은 61.4% 이며나이가증가함에따라그유 병률은점차증가하는것으로밝혀졌다 [1]. 이러한노인배 Received: March 15, 2015 Accepted: March 29, 2015 Corresponding author: Joon Chul Kim Korean Medical Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 뇨장애의적절한진단과치료를위해서는우선적으로노인배뇨장애의기전에대한이해가필요하다. 이에본문에서는노화에따른하부요로의해부학적변화와기능적변화, 그리고하부요로에영향을줄수있는노화와관련된다른인자들을기술하여노인에서배뇨장애가발생하는기전에대해알아보고자한다. 868 대한의사협회지

2 Cho KJ Kim JC Pathophysiology of LUTD in the elderly 하부요로의해부학적변화 노화는피부와점막의점진적위축, 골격근부피의감소, 평활근긴장도의저하, 신경계의변성을일으키며, 이런모든것들이하부요로기능에잠재적으로부정적영향을줄수있다. 하부요로중방광의경우노화로인한탄력조직의감소, 근육섬유접합력저하, 이차적원인에의한근육비후등은육주형성 (trabeculation) 을유발하고, 조직학적으로는방광의만성염증, 부종, 섬유화등이노화된방광에서나타날수있다. Elbadawi 등 [2] 과 Elbadawi 등 [3] 은노인배뇨장애의초미세구조연구를통해배뇨근의전자현미경상변화와요역동학적변화간의관계를조사하였는데, 정상노화방광에서는 dense band pattern, 배뇨근과활동성에서는 dysjunction pattern, 방광출구폐색에서는 myohypertrophy, 배뇨근저활동성에서는 widespread muscle degeneration 이관찰되었다고보고하였다. 노화에따른하부요로의해부학적변화는남성과여성간에차이가있는부분이있다. 노인여성에서하부요로에영향을주는주요변화중하나는폐경과관련된에스트로겐의감소이다. 생식기와하부요로는발생학적으로기원이같으며, 이들은성호르몬변화에영향을받는다. 에스트로겐수용체와프로게스테론수용체는질조직뿐만아니라, 요도, 방광, 골반저근에도분포하는데, 폐경후에스트로겐의감소는요로생식계의상피와골반지지조직의위축성변화를일으키며점막도얇아지고취약하게한다. 에스트로겐은방광의무스카린성수용체의감소 [4] 와배뇨근세포밖칼슘이온의세포안으로의이동저해 [5] 를통해서방광의배뇨근기능에직접적영향을줄수있는것으로알려져있어, 노화로인한에스트로겐감소는배뇨근과활동성과관련이있을수있다. 그리고에스트로겐은요도페쇄압력을증가시키고근위부요도로압력전달을개선시키며 [6], 요도혈관확장효과도있는것으로알려져있는데, 폐경으로에스트로겐이감소하면이런효과는저하되게된다. 에스트로겐은요로생식계의결합조직대사와콜라겐합성을촉진시키는기능도있어에스트로겐이부족할경우질과요도주위의콜라겐이감소하게되고, 이는노인여성의요실금및골반장기탈출증으로 이어질수있다 [7]. 또한에스트로겐수용체는대뇌피질, 변연계 (limbic system), 해마, 소뇌에서도존재하므로 [8] 에스트로겐의감소는배뇨를담당하는중추신경계기능에도영향을줄수있다. 남성에서노화에따른하부요로의해부학적변화중가장특징적인부분은전립선의비대이다. 전립선은간질속에가득채워져있는선 (gland) 의망상조직으로구성되어있는데, 노화는계속적인선-간질조직의상호작용의결과로전립선용적을점진적으로커지게한다. 이러한상호작용은여러가지호르몬인자와성장인자들에의해촉진된다. 특히 dihydrotestosterone과 tansforming growth factor β와같은성장인자의변화는전립선세포의증식과사멸사이불균형을일으키고, 결국전립선비대라는조직학적변화가나타나게된다 [9]. 전립선비대증은방광출구폐색을일으키고, 이는형태학적측면에서방광벽의비후를유발한다. 방광벽의비후는방광의유순도를떨어뜨리며, 방광용적을감소시키고, 배뇨근의불안정성을초래할수있고, 이런현상이장기화될경우비가역적인배뇨근수축력저하로이어지게된다. 그리고대사적측면에서는방광출구폐색으로인한배뇨근의산소대사감소가방광수축력장애의인자로거론되고있다 [10]. 하부요로의기능적변화 앞에서기술한노화로인한하부요로의해부학적변화는결국기능적변화로이어지게되며, 방광출구폐색, 배뇨근과활동성, 배뇨근수축력저하등으로나타난다. 현재하부요로기능을평가하기위한가장객관적검사방법은요역동학검사이며, 이런기능적변화에있어서도남녀간에차이가있을수있다. Madersbacher 등 [11] 은연령과요역동학적지표간의관계를남성과여성으로분리하여조사하였는데, 남성과여성모두연령이증가할수록최대요속은감소하고, 배뇨후잔뇨량은증가하며, 배뇨량과방광용적은감소하고, 최대배뇨근압과최대요속시배뇨근압은연령과관련성이없으며, 배뇨근불안정성에있어서남성에서는연령이증가할수록유의하게증가하였으나여성에서그런현상은관찰되 노인의하부요로기능변화와배뇨장애기전 869

3 J Korean Med Assoc 2015 October; 58(10): Table 1. Medications affected to lower urinary tract function Type of medication Sedatives/hypnotics Alcohol Anticholinergics Example Long-acting benzodiazepines (e.g., diazepam, flurazepam) Hydroxyzine, dicyclomine, ipratropium, solifenacin, fesoterodine Potential effects on lower urinary tract function Sedation, delirium, immobility, muscle relaxation Polyuria, frequency, urgency, sedation, delirium, immobility Urinary retention, overflow incontinence, fecal impaction Antipsychotics Haloperidol, thioridazine Anticholinergic actions, sedation, rigidity, immobility Antidepressants Amitriptyline, desipramine Anticholinergic actions, sedation Antiparkinson Trihexyphenidyl, benztropine mesylate Anticholinergic actions, sedation Opiates Morphine, tramadol Urinary retention, fecal impaction, sedation, delirium Diuretics Furosemide, thiazide Polyuria, frequency, urgency Calcium channel blockers Diltiazem, nifedipine, verapamil Urinary retention, overflow incontinence Angiotensin converting enzyme inhibitors Morphine, tramadol Cough predisposing to stress urinary incontinence α-adrenergic agonists Furosemide, thiazide Urinary retention α-adrenergic antagonists Diltiazem, nifedipine, verapamil Urethral relaxation 색없이잔뇨량이증가하는현상이동반되는데, 이를배뇨근과활동성및수축력저하 (detrusor hyperactivity with impaired contractility, DHIC) 라고부른다 [15]. 70세이상의노인을대상으로한연구에서배뇨근수축력저하가있는남성의 2/3, 여성의 1/2이방광충만기에비자발적배뇨근수축과낮은방광유순도를보였으며, 이런 DHIC 는요폐나도뇨관을유치한병력이있는경우더높은유병률을보였다고보고하였다 [16]. 지않았다. 그리고여성에서최대요도폐쇄압과기능적요도 길이가연령이증가할수록유의하게감소하였다. Pfisterer 이외의인자 하부요로에영향을주는요로 등 [12] 도연령과관련하여여성의하부요로기능이어떤변화를보이는지조사하였는데, 최대요도폐쇄압, 배뇨근수축력, 요속, 방광감각은연령이증가할수록유의하게감소하였지만, 방광용적은변화가없었고, 배뇨근과활동성이있는경우에만방광용적이감소하여, 방광용적의감소는노화자체로인한변화라기보다는배뇨근과활동성과관련된변화라고주장하였다. 하부요로증상이있는남성환자를대상으로방광유순도와연령과의관계를조사한연구가있었는데, 방광유순도는연령이증가할수록유의하게감소하는것으로보고되었다 [13]. 여러기능적변화중배뇨근수축력저하는노인배뇨장애의중요한병태생리적기전이다. 신경학적병변이없고하부요로증상을호소하는 65세이상의노인을대상으로한국내연구에서남성의 40.2%, 여성의 13.3% 가배뇨근저활동성을보였고, 나이가많아질수록그유병률은더증가하는경향을보였다 [14]. 노화는하부요로의근육성변화뿐만아니라신경계의변화도일으켜방광수축력을변화시킨다. 일부에서는배뇨근과활동성으로인한절박성요실금을호소하면서배뇨근수축력이저하되어방광출구폐 요로생식계이외의다른여러노화관련인자들이하부요로기능에영향을주어노인에서배뇨장애를유발하거나악화시킬수있다. 노인에서활동장애는흔하게나타난다. 연령이증가할수록뇌졸중, 관절염, 골절을유발하기쉬운골다공증, 절뚝거림을유발하는하지말초혈관질환, 파킨슨병과다른보행장애등의유병률도증가한다. 이런활동장애는노인이화장실에제시간에도착하지못하게하고, 결국빈뇨나요절박이있는경우요실금으로이어지게만들수있다. 또한손의적절한기능유지는제시간에배뇨를하기위해옷을벗는능력에영향을줄수있고, 심한관절염과같은상태로인해손의기능이감소한노인은이런능력이제한되어요실금을겪게된다. 노인은식사를잘못하거나수분섭취를충분히못할수있고, 이는변비나요로감염을일으킬수있으며, 하부요로증상을유발할수있다. 그리고노인의환경도영향을줄수있는데, 화장실의접근성이안좋을경우노인은배뇨를위해제시간에화장실에도착할수없게되고, 이는요실금같은배뇨장애로이어질수있다 [17]. 인지기능과감각기능의저하가노인에서더많이발생하는데, 이는노인이하부요로기능장애에대해적절히대처하기어렵게할수있다. 870 대한의사협회지

4 Cho KJ Kim JC Pathophysiology of LUTD in the elderly 예를들어알츠하이머병이나다른형태의치매가있는경우 노인은요의에대한정확한인지를할수없게되고, 혼자화 장실을가기도힘들어서요실금을보이게된다. 노인은뇌졸 중, 척추질환같은다른중추신경질환에도취약하며, 배뇨조 절에중추신경의역할을고려한다면중추신경질환이노인배 뇨장애의또다른원인이될수있다 [18]. 노인에서발생하기 쉬운내과적질환중에하부요로기능에영향을주는것들도 있다. 당뇨는삼투성이뇨작용으로다뇨를유발하며, 신경학 적변화로배뇨근과활동성을일으킬수있고, 당뇨가악화될 경우방광감각저하, 잔뇨량증가, 배뇨근수축력저하로나 타나는당뇨병성방광으로진행될수있다 [19]. 그리고울혈 성심부전이있는환자에서요실금과과민성방광의유병률이 유의하게높은것으로알려져있다 [20]. 이처럼노인은여러 가지질환이유발되기쉬우며, 이로인한다양한약제를복잡 한복용스케줄로섭취하게되고, 이런여러약제자체가하 부요로기능에영향을줄수있다 [21] (Table 1). 결론 노화에따라하부요로는구조적으로변하게되고, 이는방 광출구폐색, 배뇨근과활동성, 배뇨근수축력저하등의기 능변화를가져와하부요로증상을유발한다. 노인의배뇨장 애에는복합적기전이작용하지만어느기전이더우세하게 영향을주는지적절히판단해야할필요가있다. 찾아보기말 : 노화 ; 하부요로증상 ; 병태생리 ; 요실금 ORCID Kang Jun Cho, Joon Chul Kim, REFERENCES 1. Lee YS, Lee KS, Jung JH, Han DH, Oh SJ, Seo JT, Lee JG, Park HS, Choo MS. Prevalence of overactive bladder, urinary incontinence, and lower urinary tract symptoms: results of Korean EPIC study. World J Urol 2011;29: Elbadawi A, Hailemariam S, Yalla SV, Resnick NM. Structural basis of geriatric voiding dysfunction. VII. Prospective ultrastructural/urodynamic evaluation of its natural evolution. J Urol 1997;157: Elbadawi A, Resnick NM, Dorsam J, Yalla SV, Haferkamp A. Structural basis of neurogenic bladder dysfunction. I. Methods of prospective ultrastructural study and overview of the findings. J Urol 2003;169: Batra S, Andersson KE. Oestrogen-induced changes in muscarinic receptor density and contractile responses in the female rabbit urinary bladder. Acta Physiol Scand 1989;137: Elliott RA, Castleden CM, Miodrag A, Kirwan P. The direct effects of diethylstilboestrol and nifedipine on the contractile responses of isolated human and rat detrusor muscles. Eur J Clin Pharmacol 1992;43: Bhatia NN, Bergman A, Karram MM. Effects of estrogen on urethral function in women with urinary incontinence. Am J Obstet Gynecol 1989;160: Jackson S, James M, Abrams P. The effect of oestradiol on vaginal collagen metabolism in postmenopausal women with genuine stress incontinence. BJOG 2002;109: Maggi A, Perez J. Role of female gonadal hormones in the CNS: clinical and experimental aspects. Life Sci 1985;37: Carson C 3rd, Rittmaster R. The role of dihydrotestosterone in benign prostatic hyperplasia. Urology 2003;61(4 Suppl 1): Greenland JE, Hvistendahl JJ, Andersen H, Jorgensen TM, McMurray G, Cortina-Borja M, Brading AF, Frokiaer J. The effect of bladder outlet obstruction on tissue oxygen tension and blood flow in the pig bladder. BJU Int 2000;85: Madersbacher S, Pycha A, Schatzl G, Mian C, Klingler CH, Marberger M. The aging lower urinary tract: a comparative urodynamic study of men and women. Urology 1998;51: Pfisterer MH, Griffiths DJ, Schaefer W, Resnick NM. The effect of age on lower urinary tract function: a study in women. J Am Geriatr Soc 2006;54: Madersbacher S, Pycha A, Klingler CH, Mian C, Djavan B, Stulnig T, Marberger M. Interrelationships of bladder compliance with age, detrusor instability, and obstruction in elderly men with lower urinary tract symptoms. Neurourol Urodyn 1999;18: Jeong SJ, Kim HJ, Lee YJ, Lee JK, Lee BK, Choo YM, Oh JJ, Lee SC, Jeong CW, Yoon CY, Hong SK, Byun SS, Lee SE. Prevalence and clinical features of detrusor underactivity among elderly with lower urinary tract symptoms: a comparison between men and women. Korean J Urol 2012;53: Resnick NM, Yalla SV. Detrusor hyperactivity with impaired contractile function: an unrecognized but common cause of incontinence in elderly patients. JAMA 1987;257: Abarbanel J, Marcus EL. Impaired detrusor contractility in 노인의하부요로기능변화와배뇨장애기전 871

5 J Korean Med Assoc 2015 October; 58(10): community-dwelling elderly presenting with lower urinary tract symptoms. Urology 2007;69: Dubeau CE. The aging lower urinary tract. J Urol 2006;175(3 Pt 2):S11-S Burney TL, Senapati M, Desai S, Choudhary ST, Badlani GH. Acute cerebrovascular accident and lower urinary tract dysfunction: a prospective correlation of the site of brain injury with urodynamic findings. J Urol 1996;156: Kaplan SA, Blaivas JG. Diabetic cystopathy. J Diabet Complications 1988;2: Palmer MH, Hardin SR, Behrend C, Collins SK, Madigan CK, Carlson JR. Urinary incontinence and overactive bladder in patients with heart failure. J Urol 2009;182: Ouslander JG. Aging and the lower urinary tract. Am J Med Sci 1997;314: Peer Reviewers Commentary 본논문은나이가증가함에따라생기는하부요로기능의변화를기술하고이에따른배뇨증상이발생하는기전을서술하였다. 하부요로의해부학적변화와기능적인변화를체계적으로기술하였고하부요로에영향을주는요로이외의인자도분석되었다. 노화에따라하부요로구조가변하고이는방광출구폐색과배뇨근과활동성, 배뇨근수축저하를초래하여하부요로증상을유발함을기존보고와연구된자료를토대로기술하였다. 특히노인의경우배뇨장애는복합적인기전에의함을강조하였고이는이분야를연구함에있어서의방향을제시하였다고생각된다. [ 정리 : 편집위원회 ] 자율학습 2015 년 9 월호정답 ( 국내독버섯중독의유형과치료 ) 대한의사협회지