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by both extrinsic neural and humoral signals. Central modulation of gut motility occurs via extrinsic sympathetic and parasympathetic nerves, while gut sensation is conveyed to higher centres by both the vagus and spinal afferent nerves, with noxious signals transmitted predominantly via the latter. Descending pathways to the spinal cord modulate the transmission of sensory signals.

Pathophysiology of the ageing gut

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.

Oesophagus

      Patients with disordered oesophageal function can present with dysphagia or ‘heartburn’ or less specific symptoms such as chest pain or chronic cough. Age‐related changes in oesophageal motility are extensively documented but probably impact mainly on the very old. Classical oesophageal motility disorders like achalasia, while uncommon, can present particular challenges in the elderly. Gastro‐oesophageal reflux disease (GORD) is as prevalent as in the young, often presents atypically, and is more likely to be severe.

      Changes in oesophageal motor function related to ageing

      The oesophagus incorporates striated muscle in the upper portion and smooth muscle in the lower, with an upper oesophageal sphincter (UOS) and lower oesophageal sphincter (LOS) at either end. The term primary peristalsis refers to the coordinated sequence of contraction associated with swallowing, propagated from proximal to distal oesophagus. The LOS relaxes early in this sequence to allow the swallowed bolus to enter the stomach. Secondary peristalsis is triggered by reflux of gastric contents into the oesophagus, or experimentally by balloon distension, and serves to clear the oesophagus of acid and bile. Tertiary contractions represent spontaneous, uncoordinated oesophageal motor activity. While both tonic contraction of the LOS and its position within the diaphragmatic hiatus are important barriers against acid reflux, transient sphincter relaxations, particularly after a meal, are the most prevalent mechanism of acid reflux in the majority of GORD patients. Defences against reflux include neutralisation of acid by saliva (which contains bicarbonate) together with acid clearance by primary and secondary peristalsis.

Oesophageal motility may be evaluated by manometry, utilizing a transnasal catheter incorporating multiple closely spaced pressure sensors (either water perfused or solid state) positioned along the length of the oesophagus, including the sphincters. This technique provides information about the amplitude, duration, and propagation of pressure waves and relaxation of the sphincters, traditionally displayed as an array of line plots for each measurement site and now frequently as a pressure topography plot (Figure 17.1). The diagnosis of oesophageal motility disorders has evolved over the past decade with the Chicago Classification.¹⁸ Monitoring of pH in the distal oesophagus over 24 hours in an ambulatory setting via an electrode positioned through the nose provides valuable information about acid reflux, while multi‐channel intraluminal impedance, a technique that records electrical impedance between sequential pairs of electrodes, can be used to evaluate the flow of liquid and air in the oesophagus. Radiographic imaging of swallowed contrast can reveal abnormal oesophageal wall movements (especially cineradiography), dilatation, or delayed oesophageal transit. Transit can also be evaluated by the passage of a radiolabelled bolus, imaged by a gamma camera – a technique known as scintigraphy. While endoscopy is most useful in demonstrating mucosal lesions or strictures, it may also provide evidence of abnormal motor activity in disorders such as oesophageal spasm or achalasia.

Figure 17.1 Normal oesophageal manometry displayed as a pressure topography plot. The distance along the oesophagus is represented by the y‐axis and time by the x‐axis, with pressures colour‐coded according to the legend on the left side. During water swallows, an orderly sequence of contractions proceeds aborally (primary peristalsis). Note the high‐pressure zones of the upper (UOS) and lower oesophageal sphincters (LOS) and the swallow‐induced relaxations of the LOS.

      The effects of ageing have been studied more extensively in the oesophagus than any other gastrointestinal region, reflecting both its accessibility

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