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Hazzard's Geriatric Medicine and Gerontology, 8e

Chapter 84: Aging of the Gastrointestinal System and Selected Lower GI Disorders

AGING OF THE GASTROINTESTINAL SYSTEM

Older adults may present with unusual or subtle symptoms of serious GI disease due to alterations in physiology with aging. For example, a patient
with a GI perforation or colitis may not have guarding or significant abdominal tenderness due to decreased visceral sensitivity.

Some GI dysfunction in older patients can be attributed to the superimposed effects of chronic diseases and environmental/lifestyle exposures
(medications, alcohol, tobacco). A modest decline in function with aging, such as mild constipation, may be significant when side effects of certain
medications or concurrent disease are superimposed. The aging process per se has clinically significant effects on oropharyngeal and upper
esophageal motility (see Chapter 31), colonic function, GI immunity, and GI drug metabolism (Figure 84­1). On the other hand, because the GI tract
exhibits considerable reserve capacity, many aspects of GI function, such as intestinal secretion and absorption, are preserved with aging. A modest
decline in gastric mucosal cytoprotection or esophageal acid clearance may become significant when superimposed side effects of certain medications
or concurrent disease are also present. Common age­related changes in GI function, such as constipation, can be due to multiple causes such as
medications, pelvic floor dysfunction, or comorbidities such as progressive neurodegenerative disorders. Additional research is needed on the effects
of aging on the pathophysiology of swallowing disorders, esophageal reflux, dysmotility syndromes, GI immunobiology and microbiome, and the
cellular mechanisms of neoplasia in the GI tract. Animal studies provide important insights into the cellular physiology of aging, despite the issue of
species variation.

FIGURE 84­1.

Effects of physiologic aging on the gastrointestinal tract. This schematic diagram summarizes significant effects of aging on various divisions of the
gastrointestinal tract. Key: up arrow, increased; down arrow, decreased. LES, lower esophageal sphincter; UES, upper esophageal sphincter.

Small Intestinal Function

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relatively preserved in normal human aging. The small intestine has a large functional reserve capacity, because of
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the substantial mucosal surface area available
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with aging have been described and are summarized in Table 84­1.

TABLE 84­1
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Small Intestinal Function

Small bowel function appears to be relatively preserved in normal human aging. The small intestine has a large functional reserve capacity, because of
the substantial mucosal surface area available for secretion and absorption. Changes in small bowel epithelial development and intestinal absorption
with aging have been described and are summarized in Table 84­1.

TABLE 84­1
SMALL INTESTINAL FUNCTION

AGING EFFECTS ON SMALL INTESTINAL FUNCTION CLINICAL IMPLICATIONS

Mucosal epithelial cell regeneration ↑ Uncertain

Crypt cell proliferation ↑

Maturation and expression of brush border enzymes ↓ May affect absorption during recovery from epithelial damage due to infection or
inflammation

Specific activity of disaccharidases, aminopeptidases Absorption of lactose, mannitol and lipid unaffected in age > 60 years
unchanged

Rapidly absorbed proteins (eg, whey) ↑ Possible greater net protein gain

Specific micronutrient absorption ↓ Decreased uptake of vitamin D, folic acid, vitamin B12, calcium, copper, zinc, fatty acids,
cholesterol

Iron absorption ↓ Dietary iron content usually more than adequate to replace losses

Visceral chemosensitivity and hormone responsiveness ↑ Increased satiety

In the absence of significant small bowel damage or surgical resection, these changes are unlikely to result in significant weight loss or malnutrition.

Colonic Function

Aging is associated with diverse effects on the large intestine including alterations in mucosal cell growth, differentiation, metabolism, and immunity
(Table 84­2).

TABLE 84­2
COLONIC FUNCTION

AGING EFFECTS ON COLONIC FUNCTION CLINICAL IMPLICATIONS

1. Mucosal epithelial cell growth and differentiation altered Increased risk of colonic mucosal dysplasia and cancer

2. Release of acetylcholine in myenteric neurons ↓ Higher prevalence of constipation older than age 60
3. Calcium entry into ↓ myenteric neurons
4. Colonic muscle cells ↓

5. Nitric oxide­containing neurons in myenteric plexus ↓ Impaired relaxation of colonic muscle predisposing to development of colonic diverticulosis

These changes likely contribute to the observations of increased constipation and risk of malignancy in older adults.

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Gastrointestinal Immunity
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The GI tract is the largest immunological system in mammals. Older people appear to be more susceptible to infections that enter the body via the GI
tract, suggesting that aging may impair mucosal immunity. The GI mucosal immune response in the small intestine is a complex process that involves a
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These changes likely contribute to the observations of increased constipation and risk of malignancy in older adults.

Gastrointestinal Immunity

The GI tract is the largest immunological system in mammals. Older people appear to be more susceptible to infections that enter the body via the GI
tract, suggesting that aging may impair mucosal immunity. The GI mucosal immune response in the small intestine is a complex process that involves a
series of events: antigen uptake and presentation of antigen at the mucosal surface by specialized epithelial cells (M cells) overlying Peyer patches in
the small intestine; differentiation and migration of immunologically competent lymphocytes to the lamina propria; regulation of local antibody
production in the intestinal wall; and mucosal epithelial cell receptor–mediated transport of antibodies to the intestinal lumen. Table 84­3
summarizes the effect of aging on intestinal immunity.

TABLE 84­3
GASTROINTESTINAL IMMUNITY

AGING EFFECTS ON GASTROINTESTINAL IMMUNITY

Antigen presentation and uptake in small bowel +/­ Number of Peyer patches in small bowel +/­
Gastrointestinal T­cell immunity and recruitment ↓ ↓ Number of rectal T lymphocytes
Gastrointestinal B­cell immunity and recruitment ↓ ↓ IL­2 release
↓ Recruitment of IgA­producing B lymphocytes in small bowel
↓ IgA production

Gastrointestinal Drug Metabolism

Older patients are at increased risk for drug interactions and adverse drug reactions, primarily because of the large number of drugs and known side
effects of drugs prescribed in this age group. While most drug metabolism occurs in the liver, usually via the cytochrome P450 system, there is
expression of the CYP3A subfamily in the GI tract. This subclass oxidizes a wide variety of drugs and toxins including procarcinogens such as aflatoxins,
calcium channel antagonists, immunosuppressant agents, cholesterol­lowering agents, benzodiazepines, nonsedating antihistamines, and macrolide
antibiotics. CYP3A activity is reduced by 25% to 50% in aged individuals, explaining some of the risk for adverse drug effects.

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