김 장 환 연세의대 비뇨기과 Morphologic amp Physiologic Changes 2 Function of the Bladder Urine Storage Urine Excretion Physiologic Changes with Age Decreased detrusor ID: 225545
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Slide1
The Aging Bladder
김 장 환연세의대 비뇨기과
Morphologic & Physiologic
ChangesSlide2
2Function of the Bladder
Urine StorageUrine ExcretionSlide3
Physiologic Changes with Age
Decreased
-
detrusor
contractility
-bladder capacity
-MUCP(women)
Increased
-PVR (50-100 ml)
-
detrusor
overactivity
Slide4
Definition of the Aging Detrusor
No definition of the functional norm of the aging or aged bladderSlide5
5Normal MorphologySlide6
6Smooth Muscle
3 layers outer longitudinal middle circularinner longitudinal
Distinct 3 layers
Intertwining 3 layersSlide7
7Gross Morphologic Changes
TrabeculationThin- or thick-walled bladder
edema
diffuse scarring
chronic inflammatory lesionsSlide8
Bladder Trabeculation
a familiar gross finding at autopsyhallmark of bladder outlet obstructionThickening , hypertrophy of muscle
→ compensate for the obstruction
traditionallySlide9
Nature of Bladder Trabeculation
Obstructed bladder: may not be trabeculatedOveractive bladder: trabeculated in both sexes whether unobstructed or obstructed
Unobstructed detrusor with impaired contractility
N
europathic
bladder
B
ladder
of children with enuresis
Elbadawi
A, et al. (1993) J
Urol
150: 1668-1680
Elbadawi
A, et al. (1993) J
Urol
150: 1681-1695
Booth CM, Gosling JA. (1983). Br J
Urol
55: 367-370
Barnard RJ et.al. (1981). In: Female incontinence. pg 285-288Slide10
Nature of Bladder
TrabeculationNonspecific phenomenonReflects
characteristics of its normal construction
Cannot correlate with aging bladder
Elbadawi A, Yalla SV, Resnick NM (1993). J Urol 150: 1657-1667
Booth CM, Gosling JA (1983). Br J Urol 55: 367-370Slide11
Gross Morphology
No definite morphological characteristics of an aging bladderSlide12
Smooth muscle
Widened spaces between muscle fibersChange in collagen content Slide13
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: 122-124
Susset JG, et al, (1978) Collagen in 155 human bladders. Invest Urol 16: 204-206
Hald T, Horn T. Br J Urol. 1998;82(suppl 1):59-64.
Collagen Content in BladdersSlide14
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: 1668-1680
Elbadawi
A, et al. (1993) J
Urol
150:
1681-1695Slide15
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: 1668-1680
Elbadawi
A, et al. (1993) J
Urol
150:
1681-1695Slide16
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: 1668-1680
Elbadawi
A, et al. (1993) J
Urol
150:
1681-1695Slide17
17
C
onnexin
43
Suadiacani
S.
BJU
Int
2009
Gap junction protein
Involved in intercellular signaling
Myogenic
substrate for
detrusor
overactivitySlide18
Intrinsic Nerve
Density of cholinergic nerveReduced cholinergic and overall intrinsic innervation in obstructed human detrusorNo change in old rats
(Ordway et al)Increase in old rabbits
(
Latifpour
et al)Slide19
Histologic Changes
Collagen depositionMuscle degeneration Axonal degenerationSlide20
Neurochemcial Change
Age associated Ach responseNo change with age (Lluel et al)Contraction to Ach increase with age
(Saito, Kolta)
Response lower in elderly rats
(Toyoshima et al)Slide21
Neurochemcial Change
Age associated NE change in bladderContraction 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
bladderSlide22
Changes in beta
receptor density or sensitivity with aging is unknown in humansBladder response to beta adrenergic stimulation & receptor reduced in old male rats
Hampel
C et al.
Urologe
A. 2004 May;43(5):
535-41
Nishimoto
et al
. 1995
Neurochemcial
ChangeSlide23
Adrenergic EffectIncrease in alpha adrenergic excitatory effect
Decrease in beta adrenergic inhibitory response Net contracting effect of norephinephrine in the aged bladder23Slide24
Muscarinic &
Purinergic ReceptorsTwo 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.
2004Slide25
Muscarinic &
Purinergic Receptors
Yoshida et al. Urology 2004Slide26
Conclusions
Gross Appearance : non-specific changes
Microscopic
Appearance: collagen
increased,
Cx43
EM Appearance
: dense-band
pattern
Receptor Changes :
adrenergic,
muscarinic
↓,
purinergic
↑,
AR1D
↑ Slide27
Conclusions
Most studies using animalsMost animal studies are in vitroMost human data involve bladders with predisposing conditions (e.g. neurologic, BOO, etc)Small number in human studiesLack of longitudinal human dataImmeasurable impact on the d
iagnosis
and management of voiding disorders in the elderly
27