The Aging Bladder
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Transcript of The Aging Bladder
The Aging Bladder
김 장 환연세의대 비뇨기과
Morphologic & Physiologic Changes
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Function of the Bladder
Urine Storage
Urine Excretion
Physiologic Changes with Age
Decreased -detrusor contractility -bladder capacity -MUCP(women)
Increased -PVR (50-100 ml) -detrusor overactivity
Definition of the Aging Detrusor
No definition of the functional norm of the aging or aged bladder
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Normal Morphology
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Smooth Muscle
• 3 layers – outer longitudinal – middle circular– inner longitudinal
Distinct 3 layers
Intertwining 3 layers
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Gross Morphologic Changes
• Trabeculation• Thin- or thick-walled bladder• edema• diffuse scarring• chronic inflammatory lesions
Bladder Trabeculation
a familiar gross finding at autopsyhallmark of bladder outlet obstruction
• Thickening , hypertrophy of muscle → compensate for the obstruction
traditionally
Nature of Bladder Trabeculation
• Obstructed bladder: may not be trabeculated• Overactive bladder: trabeculated in both sexes
whether unobstructed or obstructed• Unobstructed detrusor with impaired contractility• Neuropathic bladder• Bladder of children with enuresis
Elbadawi A, et al. (1993) J Urol 150: 1668-1680Elbadawi A, et al. (1993) J Urol 150: 1681-1695Booth CM, Gosling JA. (1983). Br J Urol 55: 367-370Barnard RJ et.al. (1981). In: Female incontinence. pg 285-288
Nature of Bladder Trabeculation
• Nonspecific phenomenon
• Reflects characteristics of its normal construction
• Cannot correlate with aging bladder
Elbadawi A, Yalla SV, Resnick NM (1993). J Urol 150: 1657-1667Booth CM, Gosling JA (1983). Br J Urol 55: 367-370
Gross Morphology
• No definite morphological characteristics of an aging bladder
Smooth muscle
• Widened spaces between muscle fibers• Change in collagen content
1) Deposition of collagen and fibrosis are recognized phenomena in the aging bladders of both men and women
→ loss in compliance2) The collagen content was increased in female bladders
but decreased in male bladders → collagen/muscle ratio
Swaiman KF, Bradley WE (1967). J Appl Physiol 22: 122-124Susset JG, et al, (1978) Collagen in 155 human bladders. Invest Urol 16: 204-206Hald T, Horn T. Br J Urol. 1998;82(suppl 1):59-64.
Collagen Content in Bladders
Muscle Ultrastructure
- > 65 yrs, urodynamically stable -normally contractile -unobstructed -an asymptomatic continent person -no neurologic deficit
⇒ Dense-band pattern
Elbadawi A, et al. (1993) J Urol 150: 1668-1680Elbadawi A, et al. (1993) J Urol 150: 1681-1695
Dense-Band Pattern • Muscle cell membranes dominated by
electron-dense, conspicuously long, dense bands with markedly depleted caveolae.
• Caveolae: – small (50–100 nanometer) invaginations of the
plasma membrane– Involved in signal transduction, endocytosis,
uptake of bacteria and viruses.Elbadawi A, et al. (1993) J Urol 150: 1668-1680Elbadawi A, et al. (1993) J Urol 150: 1681-1695
Dense-Band Pattern • Dedifferentiation
mature cells (active contractile) → immature cells(inactive syntheticphenotype )
ex) arteriosclerotic blood vessels postmenopausal myometrium
Elbadawi A, et al. (1993) J Urol 150: 1668-1680Elbadawi A, et al. (1993) J Urol 150: 1681-1695
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Connexin 43
Suadiacani S. BJU Int 2009
• Gap junction protein
• Involved in intercellular signaling
• Myogenic substrate for detrusor overactivity
Intrinsic Nerve
• Density of cholinergic nerve– Reduced cholinergic and overall intrinsic
innervation in obstructed human detrusor– No change in old rats (Ordway et al)– Increase in old rabbits (Latifpour et al)
Histologic Changes
• Collagen deposition
• Muscle degeneration
• Axonal degeneration
Neurochemcial Change
• Age associated Ach response– No change with age (Lluel et al)
– Contraction to Ach increase with age (Saito, Kolta)
– Response lower in elderly rats (Toyoshima et al)
Neurochemcial Change• Age associated NE change in bladder
– Contraction to NE increase with age (Saito)
– No change in response with age (Kolta et al)
• Detrusor contraction to alpha adrenergic stimulation increased
• Aging increased expression of AR1D (alpha1D adrenergic receptor ) in the bladder
• Changes in beta receptor density or sensitivity with aging is unknown in humans
• Bladder response to beta adrenergic stimulation & receptor reduced in old male rats
Hampel C et al. Urologe A. 2004 May;43(5):535-41Nishimoto et al. 1995
Neurochemcial Change
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Adrenergic Effect
• Increase in alpha adrenergic excitatory effect
• Decrease in beta adrenergic inhibitory response
Net contracting effect of norephinephrine in the aged bladder
Muscarinic & Purinergic Receptors
• Two major components of detrusor contraction 1) by muscarinic receptors (Ach) 2) by purinergic receptors (ATP)
Yoshida et al. Urology 2004 Andersson KE, Schroder A. Urologe A. 2004
Muscarinic & Purinergic Receptors
Yoshida et al. Urology 2004
Conclusions• Gross Appearance : non-specific changes• Microscopic Appearance: collagen increased, Cx43
• EM Appearance: dense-band pattern • Receptor Changes :
adrenergic, muscarinic ↓, purinergic↑, AR1D ↑
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Conclusions• Most studies using animals• Most animal studies are in vitro• Most human data involve bladders with
predisposing conditions (e.g. neurologic, BOO, etc)
• Small number in human studies• Lack of longitudinal human data
Immeasurable impact on the diagnosis and management of voiding disorders in the elderly