Obstruction-induced pathological alterations within the urinary bladder due to Benign Prostate Hyperplasia (BPH) A review of the literature

Christos Komninos, Iraklis C. Mitsogiannis

Abstract


Introduction
Benign prostatic hyperplasia (BPH) is a frequent cause of Bladder Outlet Obstruction (BOO) and Low Urinary Tract symptoms (LUTS). BPH process
induces functional, biochemical and morphological alterations, in order for the urinary bladder to maintain a normal functionality. There is substantial
evidence that detrusor blood flow significantly decreases in the presence of BOO. This review addresses the bladder response to BOO and focuses on the alterations and biochemical adaptability of the bladder wall in the presence of hypoxia.

Methods
A literature review of published articles has been performed, including both in vivo and in vitro studies on human and animal tissue.

Results
In the presence of obstruction and hypoxia, muscle enlargement and collagen deposition comes upon, mitochondria sustain damage, mitochondrial DNA deletions and decrease mitochondrial enzyme activity occur leading to a decreased oxidative metabolism and ATP synthesis. Anaerobic metabolism and probably glycogen deposit increase, in
order for the muscle cells to find alternative energy supplies. As a result, lactic acid due to the anaerobic metabolism accumulates in the smooth
muscle causing contractile dysfunction. Furthermore, hypoxia induces bladder wall denervation and reduces cholinergic nerve density.

Conclusion
BOO is a key factor in the aetiology of LUTS/BPH. Obstruction is associated with a variety of morphological, contractile and biochemical changes within
the bladder.

Παθοφυσιολογικές μεταβολές στην ουροδόχο κύστη από την υποκυστική απόφραξη που προκαλεί η Καλοήθης Υπερπλασία του Προστάτη (ΚΥΠ).

Σκοπός: Η Καλοήθης Υπερπλασία του Προστάτη (ΚΥΠ) αποτελεί συνήθη αιτία υποκυστικής απόφραξης και πρόκλησης συμπτωμάτων από το κατώτερο ουροποιητικό σύστημα (LUTS). Στο τοίχωμα της ουροδόχου κύστης συμβαίνουν σημαντικές λειτουργικές, βιοχημικές και μορφολογικές μεταβολές κατά την εξέλιξη της ΚΥΠ, ώστε να διατηρηθεί η φυσιολογική λειτουργικότητά της. Μελέτες έχουν καταδείξει μειωμένη αιμάτωση του εξωστήρα μυός όταν υπάρχει υποκυστική απόφραξη. Η παρούσα ανασκόπηση παρουσιάζει την απάντηση της ουροδόχου κύστης κατά την υποκυστική απόφραξη και εστιάζει στις μεταβολές και βιοχημικές προσαρμογές του κυστικού τοιχώματος παρουσία της υποξίας.

Μέθοδος: Πραγματοποιήθηκε ανασκόπηση της δημοσιευμένης βιβλιογραφίας, η οποία συμπεριέλαβε in vivo και in vitro μελέτες σε ανθρώπινους και ζωικούς ιστούς.

Αποτελέσματα:
Κατά τη διάρκεια της απόφραξης και της υποξίας επέρχεται μυϊκή υπερτροφία, εναπόθεση κολλαγόνου, βλάβη στα μιτοχόνδρια, διαγραφές μιτοχονδριακού DNA και μείωση της μιτοχονδριακής ενζυμικής δραστηριότητας, με αποτέλεσμα τον μειωμένο οξειδωτικό μεταβολισμό και την ελαττωμένη σύνθεση ATP. Επίσης, παρατηρείται στροφή προς τον αναερόβιο μεταβολισμό και πιθανόν εναπόθεση γλυκογόνου, προκειμένου να ανευρεθούν εναλλακτικές πηγές ενέργειας από τα μυϊκά κύτταρα. Αποτέλεσμα αυτών των διαδικασιών είναι η συσσώρευση γαλακτικού οξέος στις λείες μυϊκές ίνες λόγω του αναερόβιου μεταβολισμού, η οποία προκαλεί
συστολική δυσλειτουργία του εξωστήρα. Επιπρόσθετα, η υποξία προάγει την απονεύρωση του τοιχώματος της κύστης και τη μείωση της πυκνότητας των χολινεργικών νευρώνων.

Συμπέρασμα: Η υποκυστική απόφραξη σχετίζεται με ποικίλες μορφολογικές και βιοχη-μικές μεταβολές στο τοίχωμα της κύστης που επηρεάζουν τη συσταλτικότητά της. Η μακροχρόνια απόφραξη μπορεί να οδηγήσει σε μη αναστρέψιμες βλάβες στον εξωστήρα μυ, με παραμονή της συμπτωματολογίας ακόμη και μετά την άρση του κωλύματος.  


Keywords


Benign prostatic hyperplasia; bladder outlet obstruction; urinary bladder; detrusor muscle; Καλοήθης Υπερπλασία Προστάτη; Υποκυστική Απόφραξη; Ισχαιμία Εξωστήρα; Συμπτώματα Κατώτερου Ουροποιητικού

Full Text:

PDF

References


Berry, S. J., Coffey, D. S., Walsh, P. C. and Ewing, L. L.: The development of human benign prostatic hyperplasia with age. J Urol, 1984;132: 474

Shapiro, E. and Lepor, H.: Pathophysiology of clinical benign prostatic hyperplasia. Urol Clin North Am,1995; 22: 285.

Andersson KE. Storage and voiding symptoms: pathophysiologic aspects. Urology 2003;62:3-10.4. Lepor H. Nonoperative management of benign prostatic hyperplasia. J Urol 1989;141:1283-9

Madsen FA, Bruskewitz RC. Clinical manifestations of benign prostatic hyperplasia. Urol Clin North Am 1995;22:291-8.

Lu SH, Chang LS, Yang AH, Lin AT, Chen KK, Wei YH. Mitochondrial DNA deletion of the human detrusor after partial bladder outlet obstruction correlation with urodynamic analysis. Uro-logy 2000;55:603-7

Lu SH, Wei YH, Chang LS, Lin AT, Chen KK, Yang AH. Morphological and morphometric analysis of human detrusor mitochondria with urodynamic correlation after partial bladder outlet obstruction. J Urol 2000;163:225-9

Backhaus BO, Kaefer M, Haberstroh KM, et al. Alterations in the molecular determinants of bladder compliance at hydrostatic pressures less than 40 cm. H2O. J Urol 2002; 168:2600-4

Yamaguchi O. Response of bladder smooth muscle cells to obstruction: signal transduction & the role of mechanosensors. Urology 2004;63:11-6

Araki I, Du S, Kamiyama M, et al. Overexpression of epithelial sodium channels in epithelium of human urinary bladder with outlet obstruction. Urology 2004; 64: 1255-60

Burkhard FC, Lemack GE, Zimmen Pe,et al. Contractile protein expression in bladder smooth muscle is a marker of phenotypic modulation after outlet obstruction in the rabbit model. J Urol 2001; 165:963-7

Uvelius B, Arner A, Malmqvist U. Contractile and cytoskeletal proteins in smooth muscle during hypertrophy and its reversal.Am J Physiol 1991; 260:C1085-93.

Sjuve R, Haase H, Ekblad E, Malmqvist U, Morano I, Arner A. Increased expression of nonmuscle myosin heavy chain-B in connective tissue cells of hypertrophic rat urinary bladder. Cell Tissue Res 2001; 304:271

Mannikarottu AS, Disanto ME, Zderic SA, Wein AJ, Chacko S. Altered expression of thin filament-associated proteins in hypertrophied urinary bladder smooth muscle. Neurourol Urodyn 2006; 25:78

Lee SD, Akbal C, Jung C. Intravesical pressure induces hyperplasia and hypertrophy of human bladder smooth muscle cells

mediated by muscarinic receptors. J Pediatric Urol 2006; 2:271-6

Deveaud CM, Macarak EJ, Kucich U, et al. Molecular analysis of collagens in bladder fibrosis. J Urol 1998; 160:1518-27

Levin R.M, Wein A.J, Butyan R, et.al: update on bladder smooth-muscle physiology. World J.Urol. 1994 12:226-232

Robert M. Levin, Niels Haugaard, Laura O’Connor, Ralph Buttyan, Anurag Das, John S. Dixon, John A. Gosling. Obstructive Response of Human Bladder to BPH vs. Rabbit Bladder Response to Partial Outlet Obstruction: A Direct Comparison. Neurourology and Urodynamics 2000;19:609

Bing W., Chang S., Hypolite J.A., DiSanto M.E., Zderic S.A., Rolf L., Wein A.J., Chacko S. Obstruction-induced changes in urinary bladder smooth muscle contractility: a role for Rho kinase. Am J Physiol Renal Physiol. 2003;285:F990

Polyák E., Boopathi E., Mohanan S., Deng M., Zderic S.A., Wein A.J., Chacko S. Alterations in caveolin expression and ultrastructure after bladder smooth muscle hypertrophy. J Urol. 2009;182:2497

Boopathi E. et al.Transcriptional Repression of Caveolin-1 (CAV1) Gene Expression by GATA-6 in Bladder Smooth Muscle Hypertrophy in Mice and Human Beings. Am J Pathol. 2011 May; 178(5): 2236

Greenland JE, Brading AF.The effect of bladder out flow obstruction on detrusor blood flow changes during the voiding cycle in conscious pigs.J Urol 2001; 165:245-8

Loran OB, Vishnevskii EL, Vishnevskii AE. The role of detrusor hypoxia in the pathogenesis of urination disorders in patients with benign prostatic hyperplasia. Urol Nefrol Mosk 1996; 6: 33-7

Elbadawi A, Meyer S, Regnier CH. Role of ischaemia in structural changes in the rabbit detrusor following partial bladder outlet obstruction: a working hypothesis and a biomechanical/structural model proposal. Neurourol Urodyn 1989; 8: 151-62

Macnab A., Stothers L.,Shadgan B. Monitoring detrusor oxygenation and hemodynamics noninvasively during dysfunctional

voiding. Advances in Urology 2012 doi:10.1155/2012/676303

Rosen R, Altwein J, Boyle P, Kirby RS, Lukacs B, Meuleman E,et al. Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7). Eur Urol. 2003;44:637-649

Rosen RC, Giuliano F, Carson CC. Sexual dysfunction and lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Eur Urol. 2005; 47: 824-837

Koritsiadis G, Stravodimos K, Koutalellis G, Agrogiannis G, Koritsiadis S, Lazaris A, Constantinides C. Immunohistochemical estimation of hypoxia in human obstructed bladder and correlation with clinical variables.BJU Int. 2008 ;102(3):328-32

Greenland JE, Hvistendahl JJ, Andersen H, et al. The effect of bladder outlet obstruction on tissue oxygen tension and blood flow in the pig bladder. BJU Int 2000;85:1109-14

Azadzoi KM, Pontari M, Vlachiotis J, et al. Canine bladder blood flow and oxygenation: Changes induced by filling, contraction and outlet obstruction. J Urol 1996;155:1459-65

Lin AT, Chen MT, Yang CH, et al. Blood flow of the urinary bladder: Effects of outlet obstruction

and correlation with bioenergetic metabolism. Neurourol Urodyn 1995;14:285-92

Chapple, C. R., Milner, P., Moss, H. E., & Burnstock, G. Loss of sensory neuropeptides in the obstructed human bladder. Br J Urol 1992;70, 373-381

Damaser MS, Haugaard N, Uvelius B. Partial obstruction of the rat urinary bladder: effects on mitochondria

and mitochondrial glucose metabolism in detrusor smooth muscle cells. Neurourol Urodyn. 1997; 16(6):601-7

Bas W.D. de Jong, Katja P. Wolffenbuttel, Jeroen R. Scheepe, Dirk

J. Kok The detrusor glycogen content of a de-obstructed bladder reflects the functional history of that bladder during PBOO. Neurourology and Urodynamics 2008; 27, 454-460

Pessina F, Solito R, Maestrini D, et al. Effect of anoxia-glucopenia and resuperfusion on intrinsic nerves of mammalian detrusor smooth muscle: Importance of glucose metabolism. Neurourol Urodyn 2005;24:389-96

Siflinger-Birnboim A, Levin RM, Hass MA.Partial outlet obstruction of the rabbit urinary UROLOGY Hellenic 29Obstruction-induced pathological alterations within the urinary bladder due to Benign Prostate Hyperplasia (BPH). A review of the literature

bladder induces selective protein oxidation. Neurourol Urodyn.2008 ;27(6): 532-9

Alex Tong-Long Lin, Ming-Shi Shiao, Ching-Ju Chen, Luke S et.al. Energetics of detrusor contraction: Effects of outlet obstruction. Neurourology and Urodynamics 1992; 11: 605-614

Zhao Y, Levin SS, Wein AJ, Levin RM. Correlation of ischemia/reperfusion or partial outlet obstruction-induced spectrin proteolysis by calpain with contractile dysfunction in rabbit bladder. Urology 1997; 49: 293-300.

Yokoyama O, Kawaguchi K, Hisazumi H. Denervation supersensitivity of the detrusor muscle due to bladder overdistension, with special reference to the relationship between supersensitivity, and changes in the connective tissue. Hinyokika Kiyo 1985; 31: 2127-34

Lin AT, Chen KK, Yang CH, Chang LS. Effects of outlet obstruction and its reversal on mitochondrial enzyme activity in rabbit urinary bladders. J Urol 1998;160: 2258-62.41. Gosling JA, Kung LS, Dixon JS, Horan P, Whitbeck C, Levin RM. 2000. Correlation between the structure and function of the rabbit urinary bladder following partial outlet obstruction. J Urol 163:1349-56

Mirone V, Imbimbo C, Longo N, Fusco F. The detrusor muscle: an innocent victim of bladder outlet obstruction. Eur Urolog 2007;51:57-66

Flameng W, Borgers M, Daenen W, Stalpaert G. Ultra-structural and cytochemical correlates of myocardial protection by cardiac hypothermia in man. J Thorac Cardiovasc Surg 1980;79:413-24

Hsu TH-S, Levin RM, Wein AJ, Haugaard N. Alterations of mitochondrial oxidative metabolism in rabbit urinary bladder after partial outlet obstruction. Mol Cell Biochem 1994;141:47-55

Campbell JD, Agubosim S,Paul RJ. Compartmentation of metabolism and function in vascular smooth muscle: quantitation of Na-pump activity and aerobic glycolysis. FASEB J 1988; 2:A755

Siegman MJ, Butler TM, Mooers SU, Davies RE.Chemical energetics of force development, force maintenance, and relaxation in mammalian smooth muscle. J Gen Physiol 1980;76:609-29

Levin RM, Haugaard N, Mogavero L, Leggett RE, Das AK. Biochemical evaluation of obstructive bladder dysfunction in men secondary to BPH: a preliminary report. Urology 1999;53: 446-50

Kato K, Lin AT-L, Wein AJ, Levin RM. Effect of outlet obstruction on glucose metabolism of the rabbit urinary bladder. J Urol 1990; 143:844-7

De Jong BWD, Wolffenbuttel K., Arentshorst ME, et al. Detrusor Glycogen reflects the functional history of bladders with partial outlet obstruction. BJU Int 2007; 100: 846-52

Haddad GG, Jiang C. O2 deprivation in the central nervous system: on mechanisms of neuronal response, differential sensitivity and injury. Prog Neurobiol 1993; 40: 277-318

GelosoDA, Levin RM. Effect of partial outlet obstruction on the myogenic response to field stimulation. Gen Pharmacol 1998;31:291-5

Martin C. Michel , Maurits M. Barendrecht. Physiological and pathological regulation of the autonomic control of urinary bladder contractility. Pharmacology & Therapeutics 2008;117:297-312

Cumming JA, Chisholm GD. Changes in detrusor innervation with relief of outflow tract obstruction. Br J Urol 1992;69:7-11




DOI: http://dx.doi.org/10.19264/hj.v26i1.53