Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 439

In rodent models of ageing, there is a substantial reduction in the number of neurons in the enteric nervous system, which becomes increasingly prominent more distally in the gut (e.g. 40% loss in the small intestine and 60% in the colon, in the myenteric plexus of rats),² and these neuronal losses parallel a decline in motility and secretion, at least in the colon.³ Similar neuronal loss is evident in the oesophagus in older humans, while in the human colon, the decline in neuron numbers begins as early as the fourth year but is most marked between young adulthood and old age.⁴ These losses are selective for cholinergic neurons and involve both the myenteric plexus (involved with initiation and control of smooth muscle contraction) and the submucous plexus (involved in secretion and absorption as well as motor control).^5,6 In ageing rats, longitudinal ileal muscle appears relatively insensitive to stimulation with acetylcholine, probably due to increased acetylcholinesterase activity.⁷ Nitrergic neurons, which generally mediate inhibitory motor responses, are protected in number but develop axonal swelling, and glial cells are also lost in parallel with neurons. Regarding the extrinsic nerve supply to the gut, the number of vagal fibres innervating the upper gastrointestinal tract does not appear to decline in ageing rats, but afferent and efferent fibres undergo morphologic changes.⁵ In particular, vagal afferents associated with both the muscle wall and the mucosa of the gut degenerate with age, potentially compromising both sensory feedback and gut reflexes.⁸ The underlying causes of neuronal loss with ageing remain unclear, although oxidative stress and/or mitochondrial dysfunction may contribute.⁹ Loss or dysfunction of interstitial cells of Cajal – specialised cells responsible for propagating the electrical rhythm that underlies muscle contraction – from the ageing human colon may contribute to a tendency to constipation.¹⁰ Limitations to our understanding of the pathophysiology of the ageing gut include a relative lack of studies relating to the upper gut and the sphincters and the paucity of human data when compared to that derived from animal models. In addition to neuronal losses, the biomechanical properties of the gut are altered with ageing in rodent models, with increased stiffness of both the oesophagus¹¹ and small intestine¹² associated with a thicker mucosa and submucosa but not an increase in thickness of the muscle layers.

The relatively good preservation of gastrointestinal motility in the healthy elderly may imply that the large number of neurons in the enteric nervous system provides a considerable functional reserve, but even this may be limited; transit of a radiolabelled meal through the upper gut occurs at a comparable rate in the healthy elderly and the young but is slightly slower through the colon in the elderly, where the loss of enteric neurons is greatest.¹³ Therefore, it may not be surprising that constipation is the one gastrointestinal complaint that is much more common in the elderly when compared to the middle‐aged.¹⁰ In the oesophagus, selective loss of intrinsic sensory neurons may explain why contractile activity in response to distension (so‐called secondary peristalsis) occurs less frequently in the healthy elderly than the young. This, together with a less compliant oesophagus, could contribute to a reduced ability to clear refluxed gastric contents.

In contrast to motor function, gut sensation is more consistently impaired with age, as reflected by a decreased perception of balloon distension in the oesophagus,¹⁴ stomach,¹⁵ and rectum¹⁶ in comparison to young subjects. A selective loss of intrinsic sensory enteric neurons may be responsible. However, the amplitude of cortical evoked potentials recorded from scalp electrodes during repeated oesophageal distension in older subjects is lower than in the young, raising the possibility that altered central processing of signals might also contribute to diminished sensation.¹⁷ In addition to mechanical stimuli, perception of chemical stimuli, such as acid, decreases with age, indicating a generalised impairment of gut sensation.