Structural Basis of Geriatric Voiding Dysfunction. III. Detrusor Overactivity

Abstract

Detrusor overactivity in the absence of outlet obstruction is common in the elderly. The few available studies on structure of the overactive detrusor generally have dealt only with its innervation. We conducted a prospective study to examine the ultrastructure of muscle cells, interstitium and nerves of the detrusor in biopsies from 35 elderly subjects to identify structural correlates of various urodynamically defined forms of voiding dysfunction. A distinctive dysjunction structural pattern was identified blindly in 15 detrusor biopsies. These patterns matched 12 women and 3 men 66 to 96 years old (mean age 79 years) who were segregated independently as a detrusor overactivity group by prospective urodynamic evaluation. All but 1 patient had incontinence and/or other symptoms, and none had diabetes or a significant neurological deficit. The dysjunction pattern was characterized by moderately widened intercellular spaces, scarce intermediate muscle cell junctions, abundant distinctive protrusion junctions and ultra-close cell abutments, and absence of profiles characteristic of enlarged hypertrophic cells. There was superimposed widespread degeneration of muscle cells and axons in 8 specimens, which matched the subgroup of patients with impaired detrusor contractility. The remaining 7 specimens with no degeneration matched the patients with normal contractility. Protrusion junctions and abutments are proposed as a possible manifestation of a process of muscle cell de-differentiation associated with natural aging, as well as the mediator in overactive detrusor of electrical coupling of muscle cells, in lieu of their normal mechanical coupling curtailed by marked reduction of intermediate cell junctions. On this basis, a bipartite myogenic mechanism is proposed to account for the involuntary contractions yet allow neurally triggered unitary voiding contractions in the overactive detrusor. Superimposed degeneration is proposed as the structural basis of impaired detrusor contractility, when also present.