Clinical aspects and therapeutic possibilities of neurogenic bladder / A neurogén húgyhólyag klinikuma és terápiás lehetoségei.

Összefoglaló. Az alsó húgyutak fo funkciója a vizelet tárolása és ürítése, amely muködések zavara az úgynevezett alsó húgyúti tünetegyüttes kialakulásához vezet, ami a kiváltó októl függoen vizeletürítési zavarral és vizeletretencióval is járhat. Kezeletlen esetekben a felso húgyutak károsodása következik be a magas hólyagnyomás által kiváltott vesicoureteralis reflux következtében, amely ureter- és veseüregrendszeri tágulat kialakulására, illetve fertozésekre és koképzodésre hajlamosít. A vizelettárolási/vizeletürítési zavarokat három fo csoportba sorolhatjuk, úgymint stressz- (terheléses) inkontinencia , hiperaktív hólyag (nedves/száraz) és neurogén hólyag. A jelen összefoglaló közlemény tárgyát képezo neurogén hólyag egy gyujtofogalom, mely magában foglal minden, releváns neurológiai kórkép talaján kialakult vizelettárolási és vizeletürítési zavart. Mivel a húgyhólyag mellett a záróizomzat és a hátsó húgycso is érintett, ezt a kórképet napjainkban "neurogén alsó húgyúti diszfunkció" elnevezéssel is szokás illetni. A kórállapotot a neurológiai diszfunkciók széles spektruma okozhatja, kezdve a helyi funkcionális zavartól a helyi idegi sérülésen át a felso és alsó motoneuron-sérülésig vagy a centrális degeneratív folyamatokig. Az eltéro etiológia ellenére a klinikai tünetek rendszerint két alapveto klinikai típusban manifesztálódhatnak: túlmuködo (fokozott detrusorkontraktilitást okozó automata) hólyag vagy alulmuködo hólyag formájában. Tekintettel a neurogén alsó húgyúti diszfunkció következtében létrejövo felso húgyúti komplikációkra, a közlemény egyik célja a betegség diagnózisát segíto algoritmus bemutatása a legújabb nemzetközi szakirodalmi ismeretek alapján. A neurogén hólyag kezelése jobbára nem terjedhet ki a kiváltó ok kezelésére, ezért a jelen összefoglaló másik célja azon gyógyszeres és invazív terápiás beavatkozások összefoglalása, melyek a felso húgyutak védelmét szolgálják az alacsony hólyagnyomás fenntartása révén. Orv Hetil. 2021; 162(4): 135-143. Summary. Storage and urination are the main functions of the lower urinary tract and its lesions lead to the so-called lower urinary tract syndrome causing either urinary incontinence or retention. In untreated cases, the upper urinary tract becomes injured via a vesicoureteral reflux resulting from increased bladder pressure and resultant dilations of the ureter and the renal pelvis which predispose to infection and stone formation. Lower urinary tract storage/urination disorders can be classified as stress incontinence, hyperactive bladder (wet/dry) and neurogenic bladder. Neurogenic bladder which is the subject of this review, is a collective term that encompasses all urinary storage and emptying disorders which develop on the basis of neurological diseases. Being not only the bladder, but also the sphincter and posterior urethra (generally termed as the "bladder outlet") affected, nowadays this condition is referred to as "neurogenic lower urinary tract dysfunction". A wide range of neurological dysfunctions could contribute to the development of this condition, ranging from local dysfunction (autonomic dysreflexia) or local nerve injury to upper/lower motoneuron injury or central degenerative processes. Regardless of the diverse etiology, the clinical symptoms eventually manifest in two major forms, i.e., overacting (automatic bladder with increased detrusor contractility) and underactive bladder. Considering the severity of complication occurring in the upper urinary tract in response to the pathophysiological changes in the lower urinary tract, one of the aims of this paper was to present an algorithm aiming to build up a state of the art diagnosis of the disease based on current international literature data. Since treatment of the neurogenic bladder usually can not target elimination of the underlying cause, the other goal of the present paper is to summarize the pharmacological treatment regimen and invasive therapeutic interventions that protect the upper urinary tract by maintaining low pressure values in the bladder. Orv Hetil. 2021; 162(4): 135-143.

Capsaicin-induced rapid neutrophil leukocyte activation in the rat urinary bladder microcirculatory bed.

AIMS: This study was initiated to investigate the involvement of neutrophil leukocyte activation in neurogenic inflammation, a process also involved in human urinary pathologies, elicited in the rat urinary bladder by the local administration of capsaicin, the archetypal TRPV1 agonist. The contribution of afferent nerves and sensory neuropeptides to leukocyte activation in the urinary bladder microcirculatory bed was examined. METHODS: Following a 15-min topical application of capsaicin (50 µM), leukocyte-endothelial interactions were examined for an observation period of 45 min with intravital microscopy. Expression of adhesion molecules E-selectin and ICAM-1 implicated in these interactions was assessed by immunohistochemistry. Selective sensory denervation was performed by neonatal treatment with capsaicin. The role of the TRPV1 receptor and two sensory neuropeptides (CGRP and substance P [SP]) were studied using the selective antagonists capsazepine, CGRP8-37 and RP67580, respectively. RESULTS: Capsaicin induced rapid increases in leukocyte rolling and adhesion and increased the expression of E-selectin and ICAM-1 in the postcapillary venules. Sensory chemodenervation via capsaicin and also TRPV1 receptor antagonism effectively prevented these changes. A similar reduction was observed in leukocyte adhesion after topical application of CGRP8-34 or RP67580, but only CGRP8-34 reduced the capsaicin-evoked leukocyte rolling. CONCLUSIONS: Topical application of capsaicin induces early neurogenically mediated cellular microcirculatory inflammatory reactions via the activation of the TRPV1 receptor and the release of CGRP and SP from sensory nerves in the bladder. Co-administration of SP and CGRP receptor antagonists may ameliorate microcirculatory inflammatory changes elicited by capsaicin in the urinary bladder.

[Experimental studies on microcirculatory inflammatory reactions of the urinary bladder]. / A húgyhólyag gyulladásos mikrokeringési reakcióinak kísérletes vizsgálata.

BACKGROUND: The vascular endothelium is a primary target of ischemia/reperfusion (IR) injury of the urinary bladder. In case of interstitial cystitis (painful bladder syndrome) or in cyclophosphamide-induced hemorrhagic cystitis, the injury is initiated at the epithelial/urothelial surface and propagates towards the interstitium, causing secondary involvement of the microvasculature. Hence the aim of our study was to assess and compare the microcirculatory aspects of the non-infectious forms of cystitis with that of IR-caused reactions. MATERIALS AND METHODS: In male Sprague-Dawley rats, interstitial cystitis was induced by intravesical instillation of protamine sulphate (2 mg in 200 µl saline for 30 min; n = 6). In another group, cyclophosphamide (75 mg/kg, ip) was administered 24 hr prior to the experiments (n = 5). In the third group, urinary bladder ischemia was induced by 60-min occlusion of the vessels supplying the bladder (n = 5). The microcirculatory inflammatory reactions were investigated by fluorescence intravital microscopy 60 min after reperfusion and 24 hr after protamine sulphate instillation or cyclophosphamide administration, respectively. In the control group, the bladder was instilled with saline (n = 5). RESULTS: Rolling of leukocytes increased ~3-fold in the postcapillary vessels in the protamine sulphate-treated group and the increase in this parameter was ~5 and ~6.5-fold in cyclophosphamide and IR groups, respectively. The increase in leukocyte adherence reached similar, approx. 7-fold increase in each of the challenged groups. The red blood cell velocity in the capillaries decreased in the protamine sulphate and IR groups, while the velocity increased moderately in the cyclophosphamide-treated group. CONCLUSIONS: Our results demonstrate that direct endothelial injury (caused by IR), as well as protamine sulphate and cyclophosphamide administrations induce inflammatory microcirculatory changes of the urinary bladder. These observations suggest a causative role for microcirculatory disturbances in the pathogenesis of interstitial cystitis and hemorrhagic cystitis as well.