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12.8: Age Relate Dysfunctions of the Digestive System - Biology

12.8: Age Relate Dysfunctions of the Digestive System - Biology


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Age-related changes in the digestive system begin in the mouth and can affect virtually every aspect of the digestive system. Neurosensory feedback is also dampened, slowing the transmission of messages that stimulate the release of enzymes and hormones.

Pathologies that affect the digestive organs—such as hiatal hernia, gastritis, and peptic ulcer disease—can occur at greater frequencies as you age. Problems in the small intestine may include duodenal ulcers, maldigestion, and malabsorption. Problems in the large intestine include hemorrhoids, diverticular disease, and constipation. Conditions that affect the function of accessory organs—and their abilities to deliver pancreatic enzymes and bile to the small intestine—include jaundice, acute pancreatitis, cirrhosis, and gallstones.

Hiatal Hernia

A hiatal hernia occurs when the hiatus becomes weakened and the junction of the esophagus and the upper portion of the stomach protrudes from the abdominal cavity into the thoracic cavity by way of the hiatus. This condition is most common in obese people over the age of 50. While the condition is initially treated with surgery it is likely to reoccur. To prevent reoccurrence the condition is treated with medication and individuals are encouraged to eat small less frequent meals and elevate the head and chest while sleeping.

Colorectal Cancer

Each year, approximately 140,000 Americans are diagnosed with colorectal cancer, and another 49,000 die from it, making it one of the most deadly malignancies. People with a family history of colorectal cancer are at increased risk. Smoking, excessive alcohol consumption, and a diet high in animal fat and protein also increase the risk. Despite popular opinion to the contrary, studies support the conclusion that dietary fiber and calcium do not reduce the risk of colorectal cancer.

Colorectal cancer may be signaled by constipation or diarrhea, cramping, abdominal pain, and rectal bleeding. Bleeding from the rectum may be either obvious or occult (hidden in feces). Since most colon cancers arise from benign mucosal growths called polyps, cancer prevention is focused on identifying these polyps. The colonoscopy is both diagnostic and therapeutic. Colonoscopy not only allows identification of precancerous polyps, the procedure also enables them to be removed before they become malignant. Screening for fecal occult blood tests and colonoscopy is recommended for those over 50 years of age.

Diverticulitis

Diverticula are tiny herniations in the wall of the intestines, producing pouches that protrude outward through the muscular layer. Fecal matter can collect in the diverticula. This causes inflammation and possible infection. The infection is called diverticulitis. Diverticulitis is common in individuals over 40 in developed countries. This is believed to be a result of diets too low in fiber.

Constipation

Constipation refers to infrequent or difficult evacuation of feces from the bowel. It is often associated with large quantities of dry, hard faces in the descending colon and rectum. This slows the movement of digestive residue. The longer the fecal matter remains in the colon the more water is removed from the matter. This exacerbates the problem.

Fecal Incontinence

Fecal incontinence, or loss of control of bowels, is a problem for many older people. The major concern for people suffering from fecal incontinence is hygiene. Additionally, fecal incontinence can be embarrassing and has been known to cause depression.

Hemorrhoids

Hemorrhoids are swollen or ruptured blood vessels in the lower bowel. Most older people suffer from this condition, and while they may not cause any discomfort hemorrhoids often cause pain, itching, and bleeding. Constipation is the most common cause of hemorrhoids.


Aging and neural control of the GI tract. I. Age-related changes in the enteric nervous system

As we enter the 21st century, the segment of the population that is the most rapidly expanding is that comprised of individuals 85 yr of age and older. Dysfunctions of the gastrointestinal (GI) system, including dysphagia, constipation, diarrhea, and irritable bowel syndrome are more common complaints of the elderly, yet our knowledge of the aging GI tract is incomplete. Compared with the rapid advances in the neurobiology of aging in the central nervous system, the understanding of age-related changes in the enteric nervous system (ENS) is poor. In this brief review, I recap experiments that reveal neurodegenerative changes and their functional correlates in the ENS of mice, rats, and guinea pigs. Clinical literature seems indicative of similar structural and functional age-related changes in the human ENS. Current studies that address the mechanisms underlying age-related changes in the ENS are introduced. The future directions for this field include physiological and pharmacological studies, especially at cellular and molecular levels. Research in the aging ENS is poised to make major advances, and this new knowledge will be useful for clinicians seeking to better understand and treat GI dysfunction in the elderly.


Digestive Problems as You Age

  • Constipation. One of the most common things we see, certainly as people are getting into their 60s and 70s, may be a change in bowel habits, predominantly more constipation," says Ira Hanan, MD, associate professor of medicine at the University of Chicago Medical Center. Symptoms include difficult or painful bowel movements, infrequent bowel movements, and hard, dry stool. There are a number of age-related factors that can cause constipation in older adults.
  • Changes in the digestive system. Your digestive system moves food through your body by a series of muscle contractions. Just like squeezing a toothpaste tube, these contractions push food along your digestive tract, Hanan says. As we age, this process sometimes slows down, and this can cause food to move more slowly through the colon. When things slow down, more water gets absorbed from food waste, which can cause constipation.
  • Medication use. Older adults take a lot of medications, says Ellen Stein, MD, an assistant professor of medicine at Johns Hopkins Hospital in Baltimore, MD. And as we age, we start to have more health problems that require medications. Several common medications can cause constipation. One example is calcium channel blockers, used for high blood pressure. "Very good for blood pressure, very constipation causing," says Stein. Narcotic pain relievers are another common culprit. An older adult who has knee or hip replacement surgery will often be given narcotics for pain. "Narcotics have effects directly on the bowel," Stein tells Web MD. "They actually slow the gut."
  • Inactivity. People often become less active as they age, says Stein, and being inactive can make you constipated. Bed rest during an illness can cause real problems. If a person has joint-replacement surgery, for example, it takes time to recover and be fully active again. Add narcotic pain relievers to the mix, and "that might change manageable constipation into something that's much more of a problem," Stein says.
  • Not drinking enough fluids. Staying hydrated helps prevent constipation at any age. It can become more of an issue for older adults who take diuretics for high blood pressure or heart failure. Diuretics lower blood pressure by causing you to lose excess fluid by urinating more often. Some people may avoid drinking too many fluids so they don't have to run to the bathroom all day long. Between urinating more and drinking less, you can become dehydrated.
  • Diverticular Disease. About half of people age 60 and older have diverticulosis. This occurs when small pouches in the lining of the colon bulge out along weak spots in the intestinal wall. While many people don't have any symptoms, gas, bloating, cramps, and constipation may occur. "I tell my patients its part of the aging of the colon," Hanan tells WebMD. "As we get older, we're more prone to developing these pockets." Why they occur with age is unclear, he says. While most of the time they don't cause a problem and don't require treatment, they can cause scarring and irregularity. If the pockets become inflamed, it's called diverticulitis, which can cause abdominal pain, cramping, fever, chills, nausea, and vomiting. Antibiotics, pain medications, and a liquid diet treat diverticulitis.
  • Ulcers &NSAIDs. Many older adults use nonsteroidal anti-inflammatory drugs (NSAIDs) to control pain from arthritis and other types of chronic pain. Regular use of NSAIDs increases the risk for stomach bleeding and ulcers. So while aging alone doesn't make your stomach more prone to ulcers, the chronic use of NSAIDs does raise your risk. More often than not older patients don't have pain from ulcers, says Hanan, but they can have painless gastrointestinal (GI) bleeding. If you notice any type of stomach bleeding, such as vomitingblood, passing dark stools, or noticing blood when you wipe, tell your doctor right away.
  • Problems with the mouth and esophagus. The esophagus is the tube that connects our mouth to our stomach. Like the colon, the esophagus can also slow down with age, moving food through more slowly. This can cause problems swallowing food or fluids. Dementia, stroke, and conditions such as Parkinson's disease can also cause difficulty swallowing.
  • Polyps. After age 50, the risk increases for developing polyps, or small growths, in the colon. Polyps may be noncancerous, they may become cancer, or they may be cancer. "We don't know what causes polyps," Hanan says. There's been speculation that it's something in the diet or something we don't get enough of, plus genetics. It's probably a cumulative effect over the years, he says. You can have polyps and not know it because they usually don't have any symptoms. "That's why screening colonoscopies are recommended for anyone over the age of 50," Hanan tells WebMD. During this procedure, polyps can be removed before they become cancer. People with a family history of colon cancer or other risk factors may need to have screenings earlier.
  • GERD. Gastroesophageal reflux disease (GERD) is the most common upper GI disorder in older adults, although people of all ages can get it. GERD occurs when stomach acid backs up into the esophagus, causing heartburn and other symptoms. Heartburn is more common as you get older, says Stein, but it's often caused by factors not related to aging. Eating late at night and eating the wrong types of foods, such as fast food and fried foods, can all cause reflux. Certain medications, including some blood pressure medications, which many older adults take, can cause heartburn. Obesity increases your risk for heartburn and GERD, so if you gain weight as you get older, you could have more reflux.

Small intestine

Aging has only minor effects on the structure of the small intestine, so movement of contents through the small intestine and absorption of most nutrients do not change much. However, lactase levels decrease, leading to intolerance of dairy products by many older adults (lactose intolerance). Excessive growth of certain bacteria (bacterial overgrowth syndrome) becomes more common with age and can lead to pain, bloating, and weight loss. Bacterial overgrowth may also lead to decreased absorption of certain nutrients, such as vitamin B12, iron, and calcium.


Bacteria in the gut may alter ageing process, finds NTU Singapore study

An international research team led by Nanyang Technological University, Singapore (NTU Singapore) has found that microorganisms living in the gut may alter the ageing process, which could lead to the development of food-based treatment to slow it down.

All living organisms, including human beings, coexist with a myriad of microbial species living in and on them, and research conducted over the last 20 years has established their important role in nutrition, physiology, metabolism and behaviour.

Using mice, the team led by Professor Sven Pettersson from the NTU Lee Kong Chian School of Medicine, transplanted gut microbes from old mice (24 months old) into young, germ-free mice (6 weeks old). After eight weeks, the young mice had increased intestinal growth and production of neurons in the brain, known as neurogenesis.

The team showed that the increased neurogenesis was due to an enrichment of gut microbes that produce a specific short chain fatty acid, called butyrate.

Butyrate is produced through microbial fermentation of dietary fibres in the lower intestinal tract and stimulates production of a pro-longevity hormone called FGF21, which plays an important role in regulating the body's energy and metabolism. As we age, butyrate production is reduced.

The researchers then showed that giving butyrate on its own to the young germ-free mice had the same adult neurogenesis effects.

The study was published in Science Translational Medicine yesterday (13 November), and was undertaken by researchers from Singapore, UK, and Australia.

"We've found that microbes collected from an old mouse have the capacity to support neural growth in a younger mouse," said Prof Pettersson. "This is a surprising and very interesting observation, especially since we can mimic the neuro-stimulatory effect by using butyrate alone."

"These results will lead us to explore whether butyrate might support repair and rebuilding in situations like stroke, spinal damage and to attenuate accelerated ageing and cognitive decline".

How gut microbes impact the digestive system

The team also explored the effects of gut microbe transplants from old to young mice on the functions of the digestive system.

With age, the viability of small intestinal cells is reduced, and this is associated with reduced mucus production that make intestinal cells more vulnerable to damage and cell death.

However, the addition of butyrate helps to better regulate the intestinal barrier function and reduce the risk of inflammation.

The team found that mice receiving microbes from the old donor gained increases in length and width of the intestinal villi - the wall of the small intestine. In addition, both the small intestine and colon were longer in the old mice than the young germ-free mice.

The discovery shows that gut microbes can compensate and support an ageing body through positive stimulation.

This points to a new potential method for tackling the negative effects of ageing by imitating the enrichment and activation of butyrate.

"We can conceive of future human studies where we would test the ability of food products with butyrate to support healthy ageing and adult neurogenesis," said Prof Pettersson.

"In Singapore, with its strong food culture, exploring the use of food to 'heal' ourselves, would be an intriguing next step, and the results could be important in Singapore's quest to support healthy ageing for their silver generation".

Group leader Dr Dario Riccardo Valenzano at the Max Planck Institute for Biology of Ageing in Germany, who was not involved in the study, said the discovery is a milestone in research on microbiome.

"These results are exciting and raise several new open questions for both biology of aging and microbiome research, including whether there is an active acquisition of butyrate producing microbes during mice life and whether extreme aging leads to a loss of this fundamental microbial community, which may be eventually responsible for dysbiosis and age-related dysfunctions," he added.

Professor Brian Kennedy, Director of the Centre for Healthy Ageing at the National University of Singapore, who provided an independent view, said, "It is intriguing that the microbiome of an aged animal can promote youthful phenotypes in a young recipient. This suggests that the microbiota with aging have been modified to compensate for the accumulating deficits of the host and leads to the question of whether the microbiome from a young animal would have greater or less effects on a young host. The findings move forward our understanding of the relationship between the microbiome and its host during ageing and set the stage for the development of microbiome-related interventions to promote healthy longevity."

The study builds on Prof Pettersson's earlier studies on how transplantation of gut microbes from healthy mice can restore muscle growth and function in germ-free mice with muscle atrophy, which is the loss of skeletal muscle mass.

Paper titled, "Gut microbiota from old mice confers neurogenic and pro-longevity signatures in young germ-free mice", published in Science Translational Medicine, 13 November 2019.

Ms Junn Loh
Manager, Media Relations
Corporate Communications Office
Nanyang Technological University, Singapore
E-mail: [email protected]

About Nanyang Technological University, Singapore

A research-intensive public university, Nanyang Technological University, Singapore (NTU Singapore) has 33,000 undergraduate and postgraduate students in the Engineering, Business, Science, Humanities, Arts, & Social Sciences, and Graduate colleges. It also has a medical school, the Lee Kong Chian School of Medicine, set up jointly with Imperial College London.

NTU is also home to world-class autonomous institutes - the National Institute of Education, S Rajaratnam School of International Studies, Earth Observatory of Singapore, and Singapore Centre for Environmental Life Sciences Engineering - and various leading research centres such as the Nanyang Environment & Water Research Institute (NEWRI) and Energy Research Institute @ NTU ([email protected]).

Ranked 11th in the world, NTU has been placed the world's top young university for the past six years. The University's main campus is frequently listed among the Top 15 most beautiful university campuses in the world and it has 57 Green Mark-certified (equivalent to LEED-certified) building projects, of which 95% are certified Green Mark Platinum. Apart from its main campus, NTU also has a campus in Novena, Singapore's healthcare district.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.


Anatomy and physiology of ageing 3: the digestive system

Ageing can have drastic effects on the functions of the digestive system. One of these is reduced appetite due to changes in hormone production and an alteration in smell and taste. Physiological changes in pharyngeal skills and oesophageal motility may lead to dysphagia and reflux. In the intestines, several factors contribute to changes in the regular gut microbial fauna, making older people more prone to bloating, pain and bacterial infection. There is also a drastic age-associated rise in the incidence of several gut pathologies including cancer of the colon. This third article in our series on the anatomy and physiology of ageing explores the digestive system.

Citation: Nigam Y, Knight J (2017) Anatomy and physiology of ageing 3: the digestive system. Nursing Times [online] 113: 4, 54-57.

Authors: Yamni Nigam is an associate professor of biomedical science John Knight is a senior lecturer in biomedical science both at the College of Human Health and Science, Swansea University.

  • This article has been double-blind peer reviewed
  • Scroll down to read the article or download a print-friendly PDF here to see other articles in this series

Introduction

The main role of the digestive system is to mechanically and chemically break down food into simple components that can be absorbed and assimilated by the body. The gut and accessory organs also play an important role in the elimination of indigestible food components, bile pigments, toxins and excess salts. The system performs a range of anatomically and physiologically distinct functions, each of which is affected differently by ageing (Fig 1).

The ‘anorexia of ageing’

Food intake diminishes with age due to a range of complex reasons that lead to reduced appetite. These include physiological changes and changes in psychosocial and pharmacological circumstances.

Appetite is controlled mainly by sensors in the gastrointestinal tract, which detect the physical presence of food and prompt the GI tract to produce a range of hormones. These are released before, during and after eating, and control eating behaviours, including the amount consumed. They include:

  • Ghrelin
  • Peptide tyrosine tyrosine (PYY)
  • Cholecystokinin (CCK)
  • Insulin
  • Leptin (Pilgrim et al, 2015).

Table 1 highlights the changes that occur in the production of these hormones with advancing age the overall result is reduced appetite.

We choose what we eat based on the smell and taste of food however, the number of olfactory receptors decreases with age and the sense of smell diminishes. US research suggests that about half of people aged 65-80 and around three-quarters of those aged over 80 years have a demonstrable loss of smell (Doty and Kamath, 2014).

This decreased sense of smell can have significant safety implications for example, a disproportionately high number of older people die from accidental gas poisoning. It can also be an early sign of neurodegenerative disorders such as Parkinson’s or Alzheimer’s disease (Hüttenbrink et al, 2013). Olfactory loss – including loss of the ability to discriminate between smells – may also be a consequence of age-related skull bone growth that results in a pinching of sensory nerve fibres.

Most older people experience regional taste deficits in the mouth. However, what is perceived as a taste defect (gustatory dysfunction) is often a primary defect in olfaction – although some studies suggest that age-related changes in the taste cell membranes diminish the sense of taste (Seiberling and Conley, 2004).

The gradual reduction in smell and taste, and therefore in appetite, leads to diminished food intake, possibly resulting in weight loss and malnutrition, while the inability to taste and enjoy food can lead to anxiety. The ability to taste salt also diminishes (Mauk, 2010) and may lead to increased consumption of salt-rich meals, which can aggravate health conditions such as hypertension. Older people should be encouraged to use herbs or mild spices in their dishes, rather than salt, if they need to add flavour.

The mouth

The lips, tongue, salivary glands and teeth all play a role in chewing, breaking down and swallowing food. Age-related shrinkage of the maxillary and mandibular bones and reduction in bone calcium content cause a slow erosion of the tooth sockets, leading to gum recession and an increased risk of root decay (Pradeep et al, 2012). People without teeth (edentulous) or who have poorly fitting dentures may find chewing difficult and, therefore, eat less and become malnourished. Alternatively, they may choose highly refined, easy-to-chew foods, thereby consuming less dietary fibre this will affect their bowel function, and may cause problems such as constipation.

A dry mouth (xerostomia) is common among older people Smith et al (2013) showed that healthy subjects aged 70 years and over produced less saliva than younger people. However, while the number of tongue acinar (saliva-producing) cells decreases with age, there is conflicting evidence as to whether the volume of saliva produced also decreases. Xerostomia can be an adverse effect of medication or can result from diseases such as diabetes. Although it is common among older people generally, it is more likely to occur in those who are taking more than four prescription drugs per day (Yellowitz and Schneiderman, 2014). Drug categories that may cause xerostomia include:

  • Diuretics
  • Antihypertensives
  • Antibiotics
  • Bronchodilators
  • Certain antidepressants.

Swallowing

Having formed a bolus of food, the mouth prepares to swallow. The bolus reaches the posterior pharyngeal wall and the musculature contracts around it swallowing occurs and food travels through the upper oesophageal sphincter into the oesophagus. With age, the muscular contractions that initiate swallowing slow down, increasing pharyngeal transit time (Nikhil et al, 2014). This may lead to swallowing difficulties (dysphagia), which can increase the risk of choking and the feeling that food is stuck in the throat. Up to 26.7% of people aged 76 years and over experience dysphagia (Baijens et al, 2016).

The oesophagus

In general, the motor function of the GI tract is relatively well preserved in healthy older people, but there are significant changes in oropharyngeal and oesophageal motility. In the very old, impaired oesophageal motility is common oesophageal peristalsis weakens with age (Gutschow et al, 2011) and peristalsis may no longer be triggered by each swallow. Both upper and lower oesophageal sphincters lose tension the lower one in particular undergoes a reduction in pressure, resulting in problems such as dysphagia, reflux and heartburn (Grassi et al, 2011). In addition, the gag reflex is absent in 43% of older people (Davies et al, 1995).

The stomach

The stomach acts as a reservoir for food, allowing us to eat at regular intervals. With age, it cannot accommodate as much food, primarily because its wall loses elasticity.

As a normal part of digestion, the stomach secretes gastric juice containing hydrochloric acid and pepsin. Although, in general, older and younger people produce gastric acid at a similar rate (Merchant et al, 2016), acid hyposecretion occurs in 10-20% of older people versus <1% of younger subjects (Gidal, 2007). This can compromise the bioavailability of certain drugs, including vitamin B12, and lead to disorders such as chronic atrophic gastritis.

There is also an age-related reduction in mucus-producing goblet cells, which results in reduced secretion of protective mucus and therefore a weakened mucosal barrier. Consequently the stomach’s lining becomes more prone to damage (Saber and Bayumi, 2016).

Gastric bicarbonate (HCO3-) and mucus normally provide an alkaline layer to defend the stomach lining against gastric juices however, research suggests that advancing age is associated with a decline in HCO3- secretion (Saber and Bayumi, 2016). The protective prostaglandin content of mucus also decreases with age, making older people more prone to gastromucosal injury such as lesions and ulcers, especially after ingesting non-steroidal anti-inflammatory drugs, which are commonly taken by older people. However, proton pump inhibitors (PPIs), which suppress acid production, are often prescribed alongside NSAIDs (Fujimori, 2015).

Finally, gastric emptying slows down with age this means food remains in the stomach for longer, prolonging satiation and reducing appetite (Nieuwenhuizen et al, 2010).

The small intestine

The main function of the small intestine is to digest and absorb food. It produces a range of digestive enzymes, supported by the pancreas and liver.

Absorption of nutrients occurs in the jejunum and ileum, the second and third regions of the small intestine. The lining of the small intestine is shaped into microscopic folds (villi), which increase the surface area available for absorption. Although an age-related reduction in villus height has been shown, the impact on nutrient uptake does not seem to be clinically significant (Drozdowski and Thomson, 2006).

There is evidence that the production of the enzyme lactase decreases with age, making older people more prone to lactose intolerance (Di Stefano et al, 2001) lactase is created following instruction from the LCT gene, which becomes less active over time.

Populations of certain bacteria that reside in the small intestine have been shown to increase as we age, leading to bloating, pain and decreased absorption of nutrients such as calcium, folic acid and iron. This can have a negative effect on health. In addition, PPIs have been shown to provoke bacterial overgrowth in the small intestine, which may exacerbate NSAID-induced small intestinal injury and foster the development of systemic conditions, including inflammatory bowel disease, diabetes and autoimmune diseases (Fujimori, 2015).

Peyer’s patches – small nodules of lymphatic tissue that form part of the gut’s immune defence system – monitor populations of intestinal bacteria to prevent the growth of pathogens. However, there is a gradual reduction in the number of Peyer’s patches in the small intestine, accompanied by a gradual loss of lymphoid follicles (Merchant et al, 2016) this can result in an uncontrolled growth of resident micro-flora.

The large intestine

As already mentioned, oesophageal peristalsis slows with age, but research has recently shown that small intestinal transit time does not seem to be affected (Fischer and Fadda, 2016). In contrast, there is an age-related slowing down of colonic transit caused by a decline in propulsive activity of the colon, which is associated with a reduction in neurotransmitters and neuroreceptors (Britton and McLaughlin, 2013). This causes a delay in colonic transit of waste, leading to constipation (Wiskur and Greenwood-Van Meerveld, 2010).

Peristalsis is also affected by the age-related atrophy of the mucosa and muscle layers of the colon. The walls of the colon sag, prompting the formation of pouches (diverticuli). Straining to eliminate faeces may put additional pressure on weakened blood vessel walls, giving rise to haemorrhoids.

The rate of cell division declines in the digestive epithelium, which cannot repair and replace itself as well as it needs to. There is also a drastic age-associated rise in the incidence of several gut pathologies including cancer of the colon – in fact, age is the key risk factor for colorectal cancer. Recent studies indicate that ageing induces changes in the DNA of epithelial intestinal cells, particularly in the colon this process – known as DNA methylation – is believed to play a significant part in the development of colorectal cancers (Masoro and Austad, 2010).

Gut microbes

Changes in the populations of gut microbes lead to an increase in facultative anaerobes – including streptococcus, staphylococcus, enterococcus and enterobacteriaceae – which are able to thrive in inflamed conditions (Pédron and Sansonetti, 2008). The ageing process mimics the intestinal microbe profile that accompanies inflammatory bowel diseases and obesity (Neish, 2009).

The commensal microorganisms inhabiting the lumen of the colon are prevented from entering surrounding tissues by a single layer of epithelial cells that form an impermeable mucosal barrier. This barrier becomes ‘leaky’ with age (Mabbott, 2015). As the barrier function of the mucosal immune system is impaired, the incidence of GI pathogen infections is higher – and is a major cause of morbidity and mortality in older people (Mabbott et al, 2015). This group is also at increased risk of infection with Clostridium difficile, which causes a potentially fatal dehydrating diarrhoea for which the two major risk factors are age of ≥65 years and exposure to antimicrobials (Jump, 2013).

The accessory organs

With age, the pancreas, which generates four major digestive enzymes, decreases in weight and some of its tissue undergoes fibrosis. Its exocrine function is impaired and the secretion of chymotrypsin and pancreatic lipase reduced (Laugier et al, 1991), adversely affecting the ability of the small intestine to digest food.

The liver undertakes more than 114 functions for the body as it shrinks with age and blood flow to it decreases, its functional capacity also decreases (Drozdowski and Thomson, 2006). There is a decrease in the rate of protein synthesis and of metabolism, the liver’s ability to detoxify many substances, as well as the production and flow of bile (involved in fat emulsification). In addition, bile becomes thicker and its salt content diminishes, resulting in higher plasma concentrations of cholesterol, particularly in women (Frommherz et al, 2016). Drugs are no longer inactivated quickly by the liver and are therefore more likely to cause dose-related side-effects: dosages therefore need to be carefully checked when prescribing for older people.

Key points

  • In older people, reduced appetite and food intake may lead to weight loss and malnutrition
  • Dry mouth is common in older people and may be a side-effect of a range of drugs
  • Significant changes in gut microbe populations that occur with age increase the risk of bacterial infection
  • With age, peristalsis slows in the oesophagus and the colon, leading to issues such as dysphagia, reflux and constipation
  • Incidence of several gut pathologies, including cancer of the colon, rises with age

Also in this series

Baijens LW et al (2016) European Society for Swallowing Disorders – European Union Geriatric Medicine Society white paper: oropharyngeal dysphagia as a geriatric syndrome. Journal of Clinical Interventions in Ageing 11: 1403-1428.

Britton E, McLaughlin JT (2013) Ageing and the gut. The Proceedings of the Nutrition Society 72: 1, 173-177.

Davies AE et al (1995) Pharyngeal sensation and gag reflex in healthy subjects. Lancet 345: 8948, 487-488.

de Boer A et al (2012) Physiological and psychosocial age-related changes associated with reduced food intake in older persons. Ageing Research Reviews 12: 1, 316-328.

de Boer A et al (2013) Physiological and psychosocial age-related changes associated with reduced food intake in older persons. Ageing Research Reviews 12: 1, 316-328.

Di Francesco V et al (2008) Effect of age on the dynamics of acylated ghrelin in fasting conditions and in response to a meal. Journal of the American Geriatrics Society 56: 7, 1369-1370.

Di Stefano M et al (2001) Lactose malabsorption and intolerance in the elderly. Scandinavian Journal of Gastroenterology 36: 12, 1274-1278.

Doty RL, Kamath V (2014) The influences of age on olfaction: a review. Frontiers in Psychology 5: 20.

Drozdowski L, Thomson ABR (2006) Aging and the intestine. World Journal of Gastroenterology 12: 47, 7578-7584.

Fischer M, Fadda HM (2016) The effect of sex and age on small intestinal transit times in humans. Journal of Pharmaceutical Sciences 105: 2, 682-686.

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Mabbott NA et al (2015) Aging and the mucosal immune system in the intestine. Biogerontology 16: 2, 133-145.

Masoro EJ, Austad SN (2010) Handbook of the Biology of Aging. Burlington, MA: Academic Press.

Mauk KL (2010) Gerontological Nursing: Competencies for Care. London: Jones and Bartlett Publishers.

Merchant HA et al (2016) Age-mediated changes in the gastrointestinal tract. International Journal of Pharmaceutics 512: 2, 382-395.

Neish AS (2009) Microbes in gastrointestinal health and disease. Gastroenterology 136: 1, 65-80.

Nieuwenhuizen WF et al (2010) Older adults and patients in need of nutritional support: review of current treatment options and factors influencing nutritional intake. Clinical Nutrition 29: 2, 160-169.

Nikhil J et al (2014) Oral and pharyngeal transit time as a factor of age, gender, and consistency of liquid bolus. Journal of Laryngology and Voice 4: 2, 45-52.

Pédron T, Sansonetti P (2008) Commensals, bacterial pathogens and intestinal inflammation: an intriguing ménage à trois. Cell Host and Microbe 3: 6, 344-347.

Pilgrim A et al (2015) An overview of appetite decline in older people. Nursing Older People 27: 5, 29-35.

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Saber A, Bayumi EK (2016) Age-related gastric changes. Journal of Surgery 4: 2-1, 20-26.

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Wiskur B, Greenwood-Van Meerveld B (2010) The aging colon: the role of enteric neurodegeneration in constipation. Current Gastroenterology Reports 12: 6, 507-512.

Yellowitz JA, Schneiderman MT (2014) Elder’s oral health crisis. Journal of Evidence-Based Dental Practice 14(Suppl): 191-200.


Anatomy and physiology of ageing 4: the renal system

The functions of the renal system include removal of waste products regulation of blood volume, blood pressure and red blood cells and balancing of electrolytes and blood pH. Renal function starts to gradually decline after the third decade of life but, in the absence of disease, the renal system is able to fulfil its role throughout life. In spite of this, many anatomical and physiological changes mean older people are prone to issues such as polyuria, nocturia and incontinence. This fourth article in our series on the anatomy and physiology of ageing explains how age affects the organs of the renal system, leading to a reduction in renal function.

Citation: Andrade M, Knight J (2017) Anatomy and physiology of ageing 4: the renal system. Nursing Times [online] 113: 5, 46-49.

Authors: Maria Andrade and John Knight are both senior lecturer in biomedical science, College of Human Health and Science, Swansea University.

  • This article has been double-blind peer reviewed
  • Scroll down to read the article or download a print-friendly PDF here to see other articles in this series

Introduction

The renal system is the most powerful regulator of the body’s internal environment. Healthy kidneys are essential to maintain homeostasis, ensuring stable conditions in which all cells can function optimally. They perform several functions (Montague et al, 2005), including:

  • Removal of waste products such as urea, uric acid, creatinine and toxic breakdown products of drugs
  • Regulation of blood volume and pressure
  • Electrolyte (salt) balance
  • Acid-base balance (regulation of blood pH)
  • Regulation of the number of erythrocytes (red blood cells)
  • Synthesis of vitamin D.

In the absence of disease, the kidneys function optimally into the third decade of life, after which there is a gradual decline in renal function (Figs 1 and 2). Around 15% of people over the age of 70 years have varying degrees of renal disease and dysfunction (Coresh et al, 2007). Factors contributing to the decline in renal function include hypertension, smoking, exposure to lead, obesity and increased inflammatory mediators in the blood (Weinstein and Anderson, 2010).

Anatomical changes

Pre-renal changes

The most important pre-renal (occurring before the kidney) change affecting kidney function is vascular degeneration. In young adults, renal blood flow is estimated to be approximately 600ml/minute in older people this is often reduced by half (Cukuranovic and Vlajkovic, 2005) primarily due to normal age-related changes in blood vessels (see part 1) and is often exacerbated in people with atherosclerosis of the renal artery.

Such blood vessel changes usually lead to ischaemia (reduced oxygenation), particularly in the outer portion of the kidney (renal cortex). Cells gradually die and are replaced with scar tissue, giving the outer surface of aged kidneys a granular or mottled appearance. The arterioles leading to the glomeruli (filtration membranes) show deposition of hyaline (clear cartilage-like material) and collagen below the endothelium this reduces the diameter of the vessels, thereby restricting blood flow. The smallest blood vessels in the kidney, including the capillaries that form the glomeruli, also progressively degenerate and are replaced with fibrous scar tissue (Musso and Oreopoulos, 2011).

Aged blood vessels experience a general reduction in the synthesis of the potent vasodilator nitric oxide (see Part 1 of this series) and this contributes to reducing blood flow to the kidneys (Weinstein and Anderson, 2010).

Reduced glomerular filtration rate

The glomerular filtration rate (GFR) is a measure of the rate of fluid filtration through the glomerular capillaries into Bowman’s capsule. It is expressed in millilitres per minute, and is routinely used to measure the progression of kidney disease. GFR peaks in the third decade of life, where it may be as high as 140ml/min/1.73m 2 . Blood vessel changes progressively reduce renal blood flow and GFR: in normal ageing, it drops by around 8ml/min per decade after the age of 30. The GFR of people in their 80s may be only 60-70% of what it was when they were young adults at 90 years of age it has typically fallen to around 65ml/min/1.73m 2 .

Reduced GFR means reduced clearance of waste products. However, age-related decline in GFR is not observed in all people indeed many maintain a stable GFR throughout life, which suggests that variables other than ageing contribute to the decline (Zhou et al, 2008).

Renal changes

Both kidney mass and weight decrease significantly after the age of 50 (Zhou et al, 2008). The kidneys of people in their 20s weigh 250-270g each in 90-year-olds this has dropped to 180-200g. It has been estimated that, between the ages of 40 and 80, approximately 20% of kidney mass is lost (Choudhury et al, 2016) only 3% of people in their 90s have histologically normal kidney tissue.

There is a gradual increase in collagen deposition, leading to progressive kidney fibrosis. In old age, whole nephrons (the functional units in the kidneys) are replaced by fatty material or scar tissue on average, 70-year-olds have lost 30-50% of their nephrons. Aged nephrons often show a variety of physical defects (Fig 2).

Glomerular abnormalities

The number of damaged glomeruli (glomerulosclerosis) increases, typically leading to progressive capillary collapse. Fewer than 5% of glomeruli show sclerosis in people in their 20s but, by their 80s, this will have risen to around 30% (Weinstein and Anderson, 2010).

Filtration membrane abnormalities

Some nephrons display a progressive thickening and wrinkling of the filtration membrane in the glomerulus and Bowman’s capsule, decreasing the renal filtering surface area. The filtration membrane also becomes increasingly permeable, allowing large molecules such as proteins to collect in the filtrate and appear in the urine (proteinuria).

Tubule abnormalities

Some kidney tubules gradually degenerate and are replaced by scar tissue (tubulo-interstitial fibrosis). This seems associated with an increasing number of cells showing features of senescence (Sturmlechner et al, 2017), which reduces the area available for the reabsorption of useful materials such as glucose, amino acids and salts. The distal convoluted tubules often shrink and may develop small pouches (distal diverticula), which can in turn become fluid-filled cysts, increasing the risk of kidney infection and pyelonephritis (Zhou et al, 2008).

Impaired renal repair

In young adult kidneys, around 1% of renal cells have the ability to divide and proliferate. This declines with age, reducing the kidneys’ ability to repair. The chemical signalling pathways that coordinate cell division and repair in the kidneys also become impaired with age (Bolignano et al, 2014).

Diet and renal ageing

Age-related changes in renal structure and function are thought to occur as a result of both genetic and environmental factors (Bolignano et al, 2014). One factor that appears to play a role is exposure to oxidative stress, which tends to lead to the release of pro-inflammatory mediators. While most oxidative stress is linked to free radicals produced during cellular metabolism, some of it comes from diet. Foods cooked at high temperature (particularly fried or roasted) are high in pro-oxidants it has been suggested that limiting their intake could reduce oxidative and inflammatory stress on the kidneys (Vlassara et al, 2009).

Gender differences in renal ageing

Although this is still poorly understood, oestrogens such as 17 beta-estradiol appear to protect the renal system in women from the effects of ageing, while androgens such as testosterone increase the risk of renal dysfunction in men. One hypothesis is that androgens promote fibrosis in the kidney this may partially explain why chronic kidney disease progresses more quickly in men (Weinstein and Anderson, 2010).

Physiological changes

Older people experience a significant reduction in renal function. Even in the absence of disease, some people over the age of 65 only possess 60% of the renal function of young adults (Razzaque, 2007). This gradual decline has major health implications, particularly when long-term conditions and circulatory problems are present.

Long-term conditions that lead to fluid overload and oedema – such as heart failure, liver disease and chronic kidney diseases (for example, diabetic and hypertensive nephropathies) – are exacerbated by poorly functioning aged kidneys. Patients with these conditions (commonly managed via diuretics) need their treatment regimens monitored and adjusted to compensate for age-related renal decline. Numerous studies have indicated that obesity, diabetes, high blood pressure, ethnicity and genetics can all contribute to the onset of renal disease in older people (Kazancioglu et al, 2013).

Common age-related physiological changes in renal function are described below.

Electrolyte imbalance

Reduced renal blood flow and GFR, together with the gradual loss of nephrons, reduce the kidneys’ ability to keep electrolytes (sodium, potassium, calcium and chloride) within optimal ranges. As these play a major role in maintaining blood pressure and generating nerve impulses, older people may experience hyper- or hypotension and confusion.

Older people are also less efficient at clearing salt, which may be due to reduced GFR (less sodium-laden blood is filtered), tubular degeneration, and reduced sensitivity to hormones such as aldosterone (Musso and Oreopoulos, 2011).

Reduced acid-base balance

While the lungs play a role in regulating blood pH, only the kidneys can excrete acidic or basic molecules directly, so they are the ultimate regulators of acid-base balance. With age, they become less efficient at clearing acidic/basic metabolites/ions due to tubule degeneration. This is problematic in older people with diabetes, as acidic molecules such as ketones may accumulate in the blood, leading to life-threatening ketoacidosis.

Reduced creatinine clearance

Creatinine is a molecule that is continually generated by skeletal muscles serum levels usually remain constant because the kidneys clear it from the blood at the same rate as it is produced. By the age of 80, clearance is reduced by around 30% (Choudhury et al, 2016) however, serum creatinine levels remain fairly constant because of the gradual reduction in skeletal muscle mass.

Polyuria and nocturia

The progressive loss of nephrons makes the kidneys less efficient at concentrating urine, therefore a greater volume of water is required to excrete toxic waste products. Additionally, the effect of antidiuretic hormone on the renal tubules is blunted in older people, leading to a larger volume of diluted urine. The result is a gradual increase in urine volume leading to polyuria (frequent urination).

In older patients, it is essential to monitor fluid status for signs of dehydration, and ensure they have free and convenient access to water. Fluids drunk during the evening take longer to be processed, potentially leading to nocturia (nocturnal urination), which is experienced by 80-90% of people aged over 80 years (Kujubu, 2009). Ideally, patients should be reminded to pass urine before going to bed to minimise the problem.

Reduced clearance of toxic metabolites

Special care must be taken with drugs that are excreted/eliminated in the urine. Dosages of water-soluble drugs – such as certain antibiotics, amphetamines and digitalis – may need adjustment according to renal function to avoid toxic accumulation. Indeed, overestimation of the GFR can lead to unexpected drug toxicity in older patients (Zhou et al, 2008). However, other organs and tissues, particularly the liver, play a role in drug metabolism and clearance, so their ageing also increases the risk of drug toxicity.

Reduced insulin clearance

The kidneys remove around 50% of secreted insulin from the peripheral blood. Although reduced GFR along with degeneration and loss of nephrons significantly diminish older people’s ability to clear it, response to insulin is gradually blunted with age, which offsets the reduced clearance (Zhou et al, 2008).

Changes in erythropoietin and vitamin D biosynthesis

The cells that form the tubules of the nephron, along with the peritubular cells, produce erythropoietin (EPO) and play a role in vitamin D biosynthesis. Tubular degeneration often leads to reductions in EPO, which can lead, in turn, to reduced erythrocyte production and to anaemia. However, some studies have demonstrated increases in EPO secretion – these may be driven by age-related resistance to the effects of this hormone (Bolignano et al, 2014).

Reduced vitamin D biosynthesis impairs the absorption of calcium and phosphate in the gut, which can contribute to osteoporosis (Zhou et al, 2008).

Post-renal changes

With age, the bladder gradually loses its elasticity due to an increase in collagen fibres in its wall. Loss in elasticity and fibrosis of the bladder can contribute to incomplete emptying during micturition (urination), particularly in men with prostate enlargement. There is conflicting evidence as to whether bladder volume changes with age: recent research suggests it rarely changes (Pfisterer et al, 2006).

Ageing and urinary incontinence

The urinary sphincter often weakens with age and this may lead to urinary incontinence – a problem often compounded by age-related changes in the nervous system. However, urinary incontinence is not a normal consequence of ageing, as many individuals never experience it, even in extreme old age.

Research indicates that around 11.6% of people aged 65-80 years experience incontinence this rises to around 35% in those over 85, and to 69% in over-85s living in nursing homes. Women seem to be at greater risk of incontinence than men (26.6-35.0% compared with 12.6-24.0% in those aged 85 years or older) this may be due to weakened pelvic floor muscles as a result of childbirth.

Incontinence can have a major negative impact on psychological wellbeing and quality of life (Ranson and Saffrey, 2015).

Ageing of the urethra and prostate

Reports on age-related changes to the female urethra are contradictory: some indicate that the urethra shrinks and its walls become thinner and atrophied (Jaipaul, 2017), while others report no evidence of change in its length (Pfisterer et al, 2006). Age-related changes in vaginal pH can encourage abnormal microbial growth, increasing the risk of urinary tract infections.

Most middle-aged and older men experience a benign enlargement of the prostate gland (prostatic hyperplasia) (Fig 3) this results in a gradual compression of the urethra, making micturition more difficult. The onset of prostate cancer is also marked by an increase in prostate size and causes a similar compression of the urethra and reduction in strength of the urine stream. Tests such as prostate-specific antigen, together with physical examination of the prostate, are often necessary to differentiate between malignancy and age-related prostatic hyperplasia.

Conclusion

Although it appears that little can be done to slow age-related changes to the renal system, research indicates that a high-protein diet can normalise GFR in some older people (Musso and Oreopoulos, 2011), potentially improving kidney function. Renal function must be assessed before making any dietary changes, as pre-existing renal disease can preclude high protein intake. In recent years a number of studies have demonstrated the anti-aging effects of calorie-restricted diets. Long-term calorific restriction appears to be effective at reducing the effects of renal ageing, with vascular damage, glomerulosclerosis and tubular fibrosis all reduced in animal models (McKiernan et al, 2007).

Although age-related decline in renal function is inevitable, the kidneys have a built-in redundancy – the renal reserve – and, in the absence of disease, will function adequately throughout life.

Key points

  • The renal system is the most powerful regulator of the body’s internal environment
  • With advancing age, renal blood flow – and therefore glomerular filtration rate – are reduced
  • The mass and weight of the kidneys decrease significantly after the age of 50 years
  • The progressive degradation of renal function leads to issues typical of old age such as polyuria, nocturia and incontinence
  • Most men experience a benign enlargement of the prostate gland as they get older, but this prostatic hyperplasia can also be a sign of malignancy

Also in this series

Bolignano D et al (2014) The aging kidney revisited: a systematic review. Ageing Research Reviews 14: 65-80.

Choudhury D et al (2016) Effect of ageing on the renal function and disease. In: Skorecki K et al (eds) Brenner and Rector’s The Kidney, Vol II. Oxford: Saunders.

Coresh J et al (2007) Prevalence of chronic kidney disease in the United States. Journal of the American Medical Association 298: 17, 2038-2047.

Čukuranović RC, Vlajković S (2005) Age related anatomical and functional characteristics of human kidney. Facta Universitatis Medicine and Biology 12: 2, 61-69.

Kazancioğlu R (2013) Risk factors for chronic kidney disease: an update. Kidney International Supplements 3: 4, 368-371.

Kujubu DA (2009) Nocturia in elderly persons and nocturnal polyuria. Geriatric Nephrology Curriculum 19.

McKiernan SH et al (2007) Adult-onset calorie restriction delays the accumulation of mitochondrial enzyme abnormalities in aging rat kidney tubular epithelial cells. American Journal of Physiology Renal Physiology 292: 6, F1751-F1760.

Montague S et al (2005) Physiology for Nursing Practice. Oxford: Baillière Tindall.

Musso CG, Oreopoulos DG (2011) Aging and physiological changes of the kidneys including changes in glomerular filtration rate. Nephron Physiology 119 (Suppl 1): 1-5.

Pfisterer MH et al (2006) The effect of age on lower urinary tract function: a study in women. Journal of the American Geriatrics Society 54: 3, 405-412.

Ranson RN, Saffrey MJ (2015) Neurogenic mechanisms in bladder and bowel ageing. Biogerontology 16: 2, 265-284.

Razzaque MS (2007) Does renal ageing affect survival? Ageing Research Reviews 6: 3, 211-222.

Sturmlechner I et al (2017) Cellular senescence in renal ageing and disease. Nature Reviews Nephrology 13: 2, 77-89.

Vlassara H et al (2009) Decline of renal function in normal aging, role of oxidants/inflammation: when does it begin: Is it inevitable, preventable, or treatable? Geriatric Nephrology Curriculum. 7.

Weinstein JR, Anderson S (2010) The aging kidney: physiological changes. Advances in Chronic Kidney Disease 17: 4, 302-307.

Zhou XJ et al (2008) The aging kidney. Kidney International 74: 6, 710-720.


Gastrointestinal Diseases

Gastrointestinal diseases affect the gastrointestinal (GI) tract from the mouth to the anus. There are two types: functional and structural. Some examples include nausea/vomiting, food poisoning, lactose intolerance and diarrhea.

What are functional gastrointestinal diseases?

Functional diseases are those in which the GI tract looks normal when examined, but doesn't move properly. They are the most common problems affecting the GI tract (including the colon and rectum). Constipation, irritable bowel syndrome (IBS), nausea, food poisoning, gas, bloating, GERD and diarrhea are common examples.

Many factors may upset your GI tract and its motility (ability to keep moving), including:

  • Eating a diet low in fiber.
  • Not getting enough exercise.
  • Traveling or other changes in routine.
  • Eating large amounts of dairy products.
  • Stress.
  • Resisting the urge to have a bowel movement, possibly because of hemorrhoids.
  • Overusing anti-diarrheal medications that, over time, weaken the bowel muscle movements called motility.
  • Taking antacid medicines containing calcium or aluminum.
  • Taking certain medicines (especially antidepressants, iron pills and strong pain medicines such as narcotics).
  • Pregnancy.

What are structural gastrointestinal diseases?

Structural gastrointestinal diseases are those where your bowel looks abnormal upon examination and also doesn't work properly. Sometimes, the structural abnormality needs to be removed surgically. Common examples of structural GI diseases include strictures, stenosis, hemorrhoids, diverticular disease, colon polyps, colon cancer and inflammatory bowel disease.

Constipation

Constipation, which is a functional problem, makes it hard for you to have a bowel movement (or pass stools), the stools are infrequent (less than three times a week), or incomplete. Constipation is usually caused by inadequate "roughage" or fiber in your diet, or a disruption of your regular routine or diet.

Constipation causes you to strain during a bowel movement. It may cause small, hard stools and sometimes anal problems such as fissures and hemorrhoids. Constipation is rarely the sign that you have a more serious medical condition.

You can treat your constipation by:

  • Increasing the amount of fiber and water to your diet.
  • Exercising regularly and increasing the intensity of your exercises as tolerated.
  • Moving your bowels when you have the urge (resisting the urge causes constipation).

If these treatment methods don't work, laxatives can be added. Note that you should make sure you are up to date with your colon cancer screening. Always follow the instructions on the laxative medicine, as well as the advice of your healthcare provider.

Irritable bowel syndrome (IBS)

Irritable bowel syndrome (also called spastic colon, irritable colon, IBS, or nervous stomach) is a functional condition where your colon muscle contracts more or less often than “normal.” Certain foods, medicines and emotional stress are some factors that can trigger IBS.

  • Abdominal pain and cramps.
  • Excess gas.
  • Bloating.
  • Change in bowel habits such as harder, looser, or more urgent stools than normal.
  • Alternating constipation and diarrhea.
  • Avoiding excessive caffeine.
  • Increasing fiber in your diet.
  • Monitoring which foods trigger your IBS (and avoiding these foods).
  • Minimizing stress or learning different ways to cope with stress.
  • Taking medicines as prescribed by your healthcare provider.
  • Avoiding dehydration, and hydrating well throughout the day.
  • Getting high quality rest/sleep.

Hemorrhoids

Hemorrhoids are dilated veins in the anal canal, structural disease. They’re swollen blood vessels that line your anal opening. They are caused by chronic excess pressure from straining during a bowel movement, persistent diarrhea, or pregnancy. There are two types of hemorrhoids: internal and external.

Internal hemorrhoids

Internal hemorrhoids are blood vessels on the inside of your anal opening. When they fall down into the anus as a result of straining, they become irritated and start to bleed. Ultimately, internal hemorrhoids can fall down enough to prolapse (sink or stick) out of the anus.

  • Improving bowel habits (such as avoiding constipation, not straining during bowel movements and moving your bowels when you have the urge).
  • Your healthcare provider using ligating bands to eliminate the vessels.
  • Your healthcare provider removing them surgically. Surgery is needed only for a small number of people with very large, painful and persistent hemorrhoids.

External hemorrhoids

External hemorrhoids are veins that lie just under the skin on the outside of the anus. Sometimes, after straining, the external hemorrhoidal veins burst and a blood clots form under the skin. This very painful condition is called a “pile.”

Treatment includes removing the clot and vein under local anesthesia and/or removing the hemorrhoid itself.

Anal fissures

Anal fissures are also a structural disease. They are splits or cracks in the lining of your anal opening. The most common cause of an anal fissure is the passage of very hard or watery stools. The crack in the anal lining exposes the underlying muscles that control the passage of stool through the anus and out of the body. An anal fissure is one of the most painful problems because the exposed muscles become irritated from exposure to stool or air, and leads to intense burning pain, bleeding, or spasm after bowel movements.

Initial treatment for anal fissures includes pain medicine, dietary fiber to reduce the occurrence of large, bulky stools and sitz baths (sitting in a few inches of warm water). If these treatments don't relieve your pain, surgery might be needed to repair the sphincter muscle.

Perianal abscesses

Perianal abscesses, also a structural disease, can occur when the tiny anal glands that open on the inside of your anus become blocked, and the bacteria always present in these glands causes an infection. When pus develops, an abscess forms. Treatment includes draining the abscess, usually under local anesthesia in the healthcare provider’s office.

Anal fistula

An anal fistula – again, a structural disease – often follows drainage of an abscess and is an abnormal tube-like passageway from the anal canal to a hole in the skin near the opening of your anus. Body wastes traveling through your anal canal are diverted through this tiny channel and out through the skin, causing itching and irritation. Fistulas also cause drainage, pain and bleeding. They rarely heal by themselves and usually need surgery to drain the abscess and "close off" the fistula.

Other perianal infections

Sometimes the skin glands near your anus become infected and need to be drained, like in this structural disease. Just behind the anus, abscesses can form that contain a small tuft of hair at the back of the pelvis (called a pilonidal cyst).

Sexually transmitted diseases that can affect the anus include anal warts, herpes, AIDS, chlamydia and gonorrhea.

Diverticular disease

The structural disease diverticulosis is the presence of small outpouchings (diverticula) in the muscular wall of your large intestine that form in weakened areas of the bowel. They usually occur in the sigmoid colon, the high-pressure area of the lower large intestine.

Diverticular disease is very common and occurs in 10% of people over age 40 and in 50% of people over age 60 in Western cultures. It is often caused by too little roughage (fiber) in the diet. Diverticulosis can sometimes develop/progress into diverticulitis

Complications of diverticular disease happen in about 10% of people with outpouchings. They include infection or inflammation (diverticulitis), bleeding and obstruction. Treatment of diverticulitis includes treating the constipation and sometimes antibiotics if really severe. Surgery is needed as last resort in those who have significant complications to remove the involved diseased segment of the colon.

Colon polyps and cancer

Each year, 130,000 Americans are diagnosed with colorectal cancer, the second most common form of cancer in the United States. Fortunately, with advances in early detection and treatment, colorectal cancer is one of the most curable forms of the disease. By using a variety of screening tests, it is possible to prevent, detect and treat the disease long before symptoms appear.

The importance of screening

Almost all colorectal cancers begin as polyps, benign (non-cancerous) growths in the tissues lining your colon and rectum. Cancer develops when these polyps grow and abnormal cells develop and start to invade surrounding tissue. Removal of polyps can prevent the development of colorectal cancer. Almost all precancerous polyps can be removed painlessly using a flexible lighted tube called a colonoscope. If not caught in the early stages, colorectal cancer can spread throughout the body. More advanced cancer requires more complicated surgical techniques.

Most early forms of colorectal cancer do not cause symptoms, which makes screening especially important. When symptoms do occur, the cancer might already be quite advanced. Symptoms include blood on or mixed in with the stool, a change in normal bowel habits, narrowing of the stool, abdominal pain, weight loss, or constant tiredness.

Most cases of colorectal cancer are detected in one of four ways:

  • By screening people at average risk for colorectal cancer beginning at age 45.
  • By screening people at higher risk for colorectal cancer (for example, those with a family history or a personal history of colon polyps or cancer).
  • By investigating the bowel in patients with symptoms.
  • A chance finding at a routine check-up.

Early detection is the best chance for a cure.

There are several types of colitis, which are conditions that cause an inflammation of the bowel. These include:

  • Infectious colitis. (cause unknown).
  • Crohn's disease (cause unknown).
  • Ischemic colitis (caused by not enough blood going to the colon).
  • Radiation colitis (after radiotherapy).

Colitis causes diarrhea, rectal bleeding, abdominal cramps and urgency (frequent and immediate need to empty the bowels). Treatment depends on the diagnosis, which is made by colonoscopy and biopsy.

Can gastrointestinal diseases be prevented?

Many diseases of the colon and rectum can be prevented or minimized by maintaining a healthy lifestyle, practicing good bowel habits and getting screened for cancer.

A colonoscopy is recommended for average-risk patients at age 45. If you have a family history of colorectal cancer or polyps, a colonoscopy may be recommended at a younger age. Typically, a colonoscopy is recommended 10 years younger than the affected family member. (For example, if your brother was diagnosed with colorectal cancer or polyps at age 45, you should begin screening at age 35.)

If you have symptoms of colorectal cancer you should consult your healthcare provider right away. Common symptoms include:

  • A change in normal bowel habits.
  • Blood on or in the stool that is either bright or dark.
  • Unusual abdominal or gas pains.
  • Very narrow stool.
  • A feeling that the bowel has not emptied completely after passing stool.
  • Unexplained weight loss.
  • Fatigue.
  • Anemia (low blood count).

Other types of gastrointestinal diseases

There are many other gastrointestinal diseases. Some are discussed, but others are not covered here. Other functional and structural diseases include peptic ulcer disease, gastritis, gastroenteritis, celiac disease, Crohn's disease, gallstones, fecal incontinence, lactose intolerance, Hirschsprung disease, abdominal adhesions, Barrett's esophagus, appendicitis, indigestion (dyspepsia), intestinal pseudo-obstruction, pancreatitis, short bowel syndrome, Whipple’s disease, Zollinger-Ellison syndrome, malabsorption syndromes and hepatitis.


Gastrointestinal Tract Disorders in Older Age

Considering an increase in the life expectancy leading to a rise in the elderly population, it is important to recognize the changes that occur along the process of aging. Gastrointestinal (GI) changes in the elderly are common, and despite some GI disorders being more prevalent in the elderly, there is no GI disease that is limited to this age group. While some changes associated with aging GI system are physiologic, others are pathological and particularly more prevalent among those above age 65 years. This article reviews the most important GI disorders in the elderly that clinicians encounter on a daily basis. We highlight age-related changes of the oral cavity, esophagus, stomach, small and large bowels, and the clinical implications of these changes. We review epidemiology and pathophysiology of common diseases, especially as they relate to clinical manifestation in elderly. Details regarding management of specific disease are discussed in detail if they significantly differ from the management for younger groups or if they are associated with significant challenges due to side effects or polypharmacy. Cancers of GI tract are not included in the scope of this article.

1. Introduction

The main characteristic of aging is progressive loss of physiological integrity which, in turn, leads to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for the majority of diseases that affect humans including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases [1]. The elderly population is currently defined as people aged 65 years or above [2], yet increasing life expectancy may move this cut off upwards in years to come. The percent of elderly population varies by country with 7.8% in Turkey, 21.5% in Germany, and 14.5% in the United States (up from 10% in the 1970s) [2]. The predicted global population over the age of 80 years is expected to be 17% by 2050 [3]. Aging affects all functions of the gastrointestinal system (GIS): motility, enzyme and hormone secretion, digestion, and absorption. The GIS also plays an essential role in medication absorption and metabolism, and it is commonly affected by side effects. While there is no GI disease that is specific and limited to advanced age, some illnesses are more prevalent in this age group and may require different management. Hence, the focus of this review is to highlight the most common diseases that affect the elderly while emphasizing details of clinical presentation and management if they significantly differ from the younger population. Age-related pathophysiology and clinical implications in elderly are the main focus.

2. Oral Cavity

Changes in the oral cavity can be caused by local trauma (ill-fitting dental prosthesis, local radiotherapy), localized benign disease (aphthous stomatitis, oral candidiasis), benign systemic disease, potentially life-threatening conditions (vitamin deficiency, Sjogren’s syndrome or Stevens-Johnson syndrome) or medication side effects (tricyclic antidepressants or antiparkinsonian drugs) [4, 5]. The most commonly reported disturbances among elderly include oral sensorial complaints (OSC), particularly dry mouth (xerostomia), taste disturbances (dysgeusia or ageusia), and burning mouth syndrome (BMS) [6]. These complaints may be explained by decrease in salivary secretion and quality of saliva associated with normal aging. Nagler and Hershkovic discovered that reduction in salivary function and altered composition are age-related [6, 7]. OSC are more prevalent in elderly than in those of age less than 65, with 50% of elderly reporting at least one of OSC. Among them, those using prescription drugs had higher prevalence of OSCs [6, 7].

Xerostomia may occur as a part of systemic disease like Sjogren’s syndrome or as a medication side effect, with tricyclic antidepressants (TCA), atropine, and antiparkinsonian drugs being the most commonly implicated medications [4]. Additionally, damage to the salivary glands following radiation for head and neck cancers can lead to permanent xerostomia. When caused by medication, it is usually reversible upon the discontinuation of the offending drug [4]. Salivary supplements can be used to treat irreversible causes.

Dysgeusia and ageusia are also frequent among elderly and are most commonly caused by medication side effects. Common offenders include lithium, metronidazole, levodopa, glipizide, captopril, and clarithromycin. Zinc deficiency is another important cause of dysgeusia, especially in elderly who are frequently malnourished [4, 8]. Diseases of the peripheral nervous system (Bell’s palsy) are more commonly associated with taste disturbances than are central nervous system disorders [8].

Oropharyngeal dysphagia is defined as a sensation of difficulty chewing food or initiation of swallowing [9], and results from changes affecting the complex neuromuscular mechanism that coordinates the tongue, pharynx, and upper esophageal sphincter (UES). The most common causes of oropharyngeal dysphagia are neuromuscular disorders such as stroke, multiple sclerosis, myasthenia gravis, dementia, Parkinson’s disease, and muscular dystrophy. Pharyngeal cancers and strictures are local mechanical causes [10, 11]. Cough with swallowing, food sticking in the throat and nasal regurgitation are common signs of dysphagia and all increase risk for aspiration. Oropharyngeal dysphagia affects up to 13% of individuals above age of 65 and up to 50% of nursing home residents suffer from it [9, 12]. Elderly are usually not aware of their swallowing problems and might not seek help until complications such as aspiration pneumonia, malnutrition, or dehydration develop. Diagnosis is based on detailed history and by video fluoroscopic examination [5]. In many cases patients need artificial modes of feeding due to the irreversible nature of the underlying disease [10]. Table 1 summarize diseases of oral cavity in elderly.

3. Esophagus

Presbyesophagus is a term coined in 1964 [13] to describe the aging esophagus and changes that occur along this process. Over the last 40 years, with the development of more sophisticated diagnostic techniques, our understanding about age-related changes in the esophagus has evolved and current opinion is that presbyesophagus, in its original meaning, does not exist [14]. Esophageal problems in the elderly are more related to other co-morbidities rather than esophagus itself. The term presbyphagia is now used to describe characteristic physiologic changes in swallowing associated with the advanced age. While these changes are physiologic, they do increase the risk of dysphagia and aspiration in elderly, especially during acute illnesses and other stressors [14]. Studies have yielded conflicting results regarding esophageal motility in the elderly. Ferriolli et al. [15] demonstrated even healthy elderly patients exhibited significant changes in esophageal peristalsis and delayed esophageal emptying when compared to younger age groups. Two other studies [16, 17] found a significant decrease in peristaltic wave amplitudes as well as decreased LES and UES pressures. These studies demonstrated that the number of failed esophageal contractions and the duration of peristaltic contraction significantly increase in the elderly. Contrary to these studies, a retrospective study by Robson and Glick failed to demonstrate any significant difference in LES pressures and peristaltic duration and amplitude [18]. Finally, the most recent study by Besanko et al. [19] found only subtle changes in LES pressure and relaxation associated with aging. On the cellular level, these changes may be explained by loss of intrinsic enteric neurons which, in some studies have been shown to be more vulnerable to age-related degeneration and death than the other parts of the nervous systems. In particular cholinergic myenteric neurons seem to be more vulnerable than the other enteric neurons [20].

Esophageal dysphagia is most commonly manifested as the feeling of food being stuck in the chest. It can be caused by mechanical obstruction inside the esophagus itself (stricture, tumor) or compression from surrounding tissues (vascular compression or mediastinal masses). Neuromuscular causes include achalasia, scleroderma, or diffuse esophageal spasm. Finally, inflammatory and infectious causes can lead to esophageal dysphagia (eosinophilic esophagitis, candidiasis). Endoscopy is an essential part of the evaluation and can diagnose the majority of these conditions [9].

Odynophagia is painful swallowing. Infection and malignancy are the most common causes. Candida, herpes simplex virus, and cytomegalovirus are the most commonly found pathogens in infectious cases, especially in immunocompromised patients [21]. Several studies indicate elderly patients require more stimuli to perceive the disturbance and have a higher threshold for the sensation of pain [22, 23]. Lasch et al. [23] showed that elderly, nondiabetic patients required significantly higher mean balloon volumes to sense pain when compared to younger individuals. This may be explained by the previously mentioned age-related decrease of myenteric neurons. As a consequence, elderly patients frequently seek help late, when their disease is in advanced stage.

Gastroesophageal reflux disease (GERD) is a “condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications” unlike nonproblematic gastroesophageal reflux which is a physiological event that occurs during and after meals [24]. The prevalence of GERD among the elderly is about 23% and it was one of the most commonly found conditions among almost 20,000 nursing home residents in the study by Moore et al. [25]. While one would expect that prevalence of GERD increases with age due to multiple reasons (decreased saliva production and increased prevalence of motility disorders and hiatal hernia), studies demonstrated similar prevalence of GERD among older and younger age groups [26, 27]. However, severity of GERD and its associated complications (such as Barrett’s esophagus, severe esophagitis, ulcerations and strictures) are more prevalent in the elderly [28, 29]. The most common symptom associated with GERD is heartburn. The frequency of severe heartburn seems to decline with age and the elderly might have atypical signs of GERD such as dysphagia or odynophagia [28]. This atypical presentation may relate to a decrease in esophageal pain perception and an increase in the prevalence of atrophic gastritis. Proton pump inhibitors (PPI) are the mainstay of treatment [29], yet the side effects associated with PPI therapy (increased risk of osteoporosis, development of Clostridium difficile colitis (CDC), interstitial nephritis, and community acquired pneumonia) should be kept in mind. While some authors voice concern regarding antireflux surgery in this age group [30], laparoscopic antireflux surgery should be considered in selected groups of patients. It appears to be a safe and effective treatment for GERD in elderly with low morbidity and mortality rates and excellent results [31].

Barrett’s columnar-lined esophagus (CLE) is defined as a replacement of the normal distal esophageal squamous epithelium by metaplastic columnar epithelium, which is thought to be caused by prolonged GERD [32, 33]. The most feared complication of Barrett’s esophagus is development of high grade dysplasia and adenocarcinoma. The incidence of adenocarcinoma in Barrett’s esophagus has been estimated to be around 0.5% annually and slightly lower at 0.32% in patients without dysplasia at index endoscopy [33, 34]. A study by Gatenby et al. [33] found that risk of low grade dysplasia was independent of age at surveillance, yet they found that increasing age is an important risk factor for development of high-grade dysplasia and adenocarcinoma. The mean age at diagnosis of Barrett’s esophagus was 61.6 and 67.3 years in males and females, respectively, and the mean life expectancy at diagnosis was 23.1 years in males, 20.7 years in females [35]. These findings indicate Barrett’s esophagus is more prevalent among elderly. As previously mentioned (see chapter about GERD) older patients may be asymptomatic or have atypical symptoms, leading them to present late when complications may have already developed. Patients who are diagnosed with CLE may be offered surveillance in an attempt to detect dysplasia and potentially curable cancer. However, co-morbidities, life expectancy at the time of CLE diagnosis, and yearly risk of development of adenocarcinoma should be considered. A cross sectional study done by Myung S. Ko et al. found that one third of older men diagnosed with CLE had limited life expectancy [36]. They further argued that elderly patients are more likely to experience harms of surveillance than benefit from timely detection of dysplasia or early cancer and suggested that it should not be the routine strategy in this patient population.

Medication induced esophagitis (pill esophagitis) refers to the inflammation of the esophagus from harmful effects of medication due to their altered passage through esophagus and increased contact with esophageal mucosa. While it can occur at any age, it is more prevalent in elderly patients [37]. Polypharmacy, decrease in esophageal motility, and taking medication with insufficient amounts of water are factors most commonly associated with pill esophagitis in elderly [38]. Additionally, patients with cardiomegaly can develop esophageal compression from enlarged left atrium, placing them at increased risk for medication induced esophagitis. Abid et al. found female gender, presence of diabetes, and ischemic heart disease, in addition to advanced age, to be associated with pill esophagitis [38]. The most commonly implied causative agents include nonsteroidal anti-inflammatory drugs (NSAID), aspirin, doxycycline, bisphosphonates, ferrous sulfate, and captopril. The most common symptoms are chest pain (71.8%) and odynophagia (38.5%) [39]. Detailed history, availability of accurate medication list, and endoscopy are invaluable in establishing the diagnosis. Endoscopic findings show ulceration in more than 80% of cases, while kissing ulcers are present in up to 42% of patients [39]. The mainstay of treatment is withdrawal of the inciting medication and use of PPIs, leading to a favorable prognosis in most cases. Table 2 summarize diseases of esophagus in elderly.

4. Stomach

Altered gastric microbiota, reduced mucosal protective mechanisms, decreased gastric blood flow, and consequently compromised repair mechanisms are the hallmarks of age-related gastric changes [40, 41]. These changes make older people more susceptible to the development of several diseases, such as gastric ulcer, atrophic gastritis, and peptic ulcer disease [41]. Additionally, elderly are more likely to experience medication related gastrointestinal side effects which, in turn, can decrease their medication adherence and further contribute to morbidity and mortality. The effect of age on gastric motility has been a subject of debate resulting in numerous studies reporting conflicting evidence. Using gamma camera technique, Madsen et al. [42] showed that gastric and small bowel motility were not reduced in healthy elderly subjects (mean age 81 year) when compared to control group (mean age 24 year). Additionally, they found that neither gender nor body mass index (BMI) influenced gastric and small bowel transit time. In contrast, a study by Shimamoto et al. [43] demonstrated significant decrease in postprandial gastric contractile force. They also found that this reduction was more pronounced among elderly who led less active lifestyles. Among the co-morbidities frequently encountered among older people, Parkinson’s disease and diabetes mellitus seem to have the greatest impact on gastric emptying [44]. Loss of cholinergic enteral neurons seems the most plausible explanation for decreased motility in elderly. Although not yet seen in human studies, the current evidence for loss of these neurons is derived from animal models using rodents (rat, mouse and guinea pig). While there is so much more to discover about enteric neurodegeneration that occurs with aging, it seems reactive oxygen species (ROS) may play a central role and that, despite the absence of neurogenesis, the GIS has significant functional reserve as evidenced by relatively preserved function despite dramatic loss of enteric neurons [20].

Chronic atrophic gastritis (CAG) is more prevalent in the elderly and is associated with H. pylori infection [45]. The hallmark of disease is the partial loss of glands in the gastric mucosa leading to hypochlorhydria or achlorhydria. The prevalence of CAG is higher in elderly and there are significant geographical variations showing elderly from China and Japan are particularly affected with a prevalence of up to 50% in those above age 60 years [45, 46]. While advanced age was thought to be independently related to chronic atrophic gastritis in the past, current data support the theory that atrophic changes of the gastric mucosa are associated with H. pylori infection rather than the age itself [47]. Gastritis activity can be decreased by eradication of H. pylori [47, 48]. In their study, Kokkola et al. [49] demonstrated that elderly patients who successfully eradicated infection had significantly lower mean histological scores of inflammation, atrophy, and intestinal metaplasia. Decrease in acid secretion as a consequence of chronic atrophic gastritis leads to two problems that are particularly prominent in the elderly population: small intestinal bacterial overgrowth (SIBO) and malabsorption [50, 51]. A study by Parlesak et al. examined prevalence of SIBO using hydrogen breath test and found the prevalence in elderly was 15.6% compared to 5.9% found in younger age groups [51]. Several studies examined the association between CAG and other co-morbidities in elderly. A cross sectional study by Hye Won et al. found significant association between presence of CAG and development of osteoporosis in elderly females in Korea [52]. They explained their findings were a result of decreased calcium absorption secondary to hypochlorhydria or achlorhydria leading to decreased bone mineral density. Another cross sectional study [53] found a positive association between autoimmune thyroid disease and CAG. The authors suggested that autoimmune thyroid disease and atrophic body gastritis occur in a closely linked fashion, particularly in females with positive parietal cell antibodies. Although data are still somewhat conflicting, recent studies suggest that eradicating H. pylori infection in elderly patients may prevent progression from CAG to intestinal metaplasia and gastric cancer (GC) [54]. Emerging knowledge about the changes in human gastric microbiota associated with aging has shed new light on its association with gastric cancer. Pearson and co-authors [41] showed that gastric microbiota varies for patients with autoimmune and H. Pylori associated atrophic gastritis, with former expressing higher bacterial diversity and abundance. Both conditions are associated with reduction in gastric acid secretion and development of gastric cancer (particularly neuroendocrine and gastric adenocarcinoma), while people treated with PPIs maintain normal gastric microbiota diversity in spite of hypochlorhydria [41].

H. pylori infection prevalence in developing countries is the highest among the children, while in developed countries is higher with increasing age [55]. This marked difference is most likely due to a cohort effect of the earlier generation exposed to poor sanitation [47] which is a known risk factor for contracting the infection. On the global level, 50% of people are colonized by H. pylori [56] and the prevalence varies from 7% to 87% [55]. Apart from being associated with peptic ulcer disease, H. pylori is identified as a type I carcinogen associated with gastric adenocarcinoma and gastric non-Hodgkin’s lymphoma [57, 58]. Severity of upper gastrointestinal symptoms secondary to H. pylori infection seems to be higher in the elderly [47]. Several extra intestinal disorders have been associated with H. pylori seropositivity. The most notable of these for older adults include cardiovascular diseases, osteoporosis, and neurocognitive impairment. Several studies have established association between H. pylori infection and cardiovascular diseases [59, 60], yet a few other studies failed to find any association [61, 62]. Chronic inflammation secondary to ongoing H. pylori infection may play a role in developing or worsening Alzheimer dementia [63–65] and vascular dementia [66]. The association between compromised bone mineral density and H. pylori infection has been supported by recent investigations [52, 67]. Despite evidence associating H. Pylori infection with extra intestinal diseases (dermatological, neurologic, cardiovascular and hematologic), further studies are needed to confirm this relationship [68]. Current evidence indicates H. Pylori’s strongest associations are with iron deficiency anemia (IDA) and immune thrombocytopenic purpura (ITP)[68].

Peptic ulcer disease (PUD) encompasses both gastric and duodenal peptic injury that leads to a break in gastric or duodenal mucosa and, more rarely, in the esophagus or Meckel’s diverticulum [69]. The majority of ulcers in elderly is caused by H. pylori infection or is associated with the use of NSAIDs/aspirin [69, 70]. Unlike in general population, the incidence and mortality from PUD in elderly remains very high [71]. Gastric ulcers in elderly are usually larger and tend to occur higher in the stomach on the lesser curve [72]. The main factors contributing to this are a higher prevalence of H. pylori infection among elderly, increased NSAIDs/aspirin use, and polypharmacy including medications associated with increased risk of PUD (anticoagulants, selective serotonin reuptake inhibitors (SSRIs), and oral steroids). The physiologic changes associated with old age that contribute to this include reduced blood flow through GI system and decreased secretion of key components of gastrointestinal protective mechanisms such as bicarbonates, mucin, and prostaglandins [71]. Gastric acid secretion is unaffected in healthy elderly [73], but H. pylori infection associated changes in gastric microbiota and atrophic gastritis both lead to hypochlorhydria and a decline in gastric acid secretion in older adults [5, 41].

Clinical manifestation of PUD in elderly is often atypical. In their prospective study, Hilton et al. demonstrated that only 30% of elderly patients with endoscopy proven PUD had typical epigastric pain [74]. Additionally, elderly patients with acute gastric or duodenal ulcer perforation might not exhibit classic signs of chemical peritonitis [75], which is partially due to hypochlorhydria observed in this age group. While medical treatment of PUD in elderly is not significantly different than in younger patients, medication side effects and interactions must be kept in mind. Many elderly have a strong concomitant indication for antiplatelet or anticoagulant agents, making exploring both individualized risks and benefits of continuing those along with H2 blockers or proton pump inhibitors (PPIs) crucial. There is emerging evidence that PPIs are associated with community acquired pneumonia (CAP), Clostridium difficile colitis (CDC) and osteoporosis, all of which tend to be more severe in elderly. Significant correlation between hip fractures and the use of PPIs in elderly has also been reported, leading to concerns that duration of treatment should depend on indication and should not be universally lifelong [76]. Elderly with bleeding PUD who underwent open surgical repair had significantly higher 30 day morbidity and mortality then younger counterparts [77]. A retrospective study by Fezzi at all [78] analyzed outcomes for 98 patients admitted for bleeding peptic ulcer and found that 66% achieved hemostasis endoscopically. They found repeated endoscopic treatment was not associated with increased mortality and recommended repeated endoscopy in elderly with elevated surgical risk. Trans-catheter arterial embolization was another option to consider in this group based on the same study. Table 3 summarize diseases of stomach in elderly.

5. Small Intestine

The hormonal secretion and absorptive function of the small intestine in older adults is not significantly different in comparison to younger counterparts [5]. Minimal changes in small bowel motility as well as reduced mucosal immunity are seen, but they are clinically insignificant in the absence of co-existing illness. While some animal studies demonstrate age-related changes in small intestinal morphology such as increase in villous width and height and reduction in mucosal surface area, human studies did not find such changes [79]. There are few human studies on this topic and while some morphologic changes may occur they usually are not severe enough to be a cause of malabsorption [80]. The studies done by Ciccocioppo and Corazza [81, 82] showed that increase in proliferation and differentiation rates of enterocytes maintains unchanged intestinal architecture with increased expression of proliferating cell nuclear antigen in elderly compared to younger age groups.

Celiac disease (CD) is a chronic, systemic autoimmune disease that affects genetically predisposed individuals secondary to exposure to dietary gluten protein [83]. The classic form of CD manifests as a malabsorption syndrome associated with chronic diarrhea, mineral deficiencies, failure to thrive, and weight loss. Many patients have only extra intestinal manifestations or even no symptoms at all. These forms are termed atypical and silent celiac disease, respectively [84]. In patients who suffer from celiac disease, tissue transglutaminase (TTG) binds to gliadin in the gut level. Antigen presenting cells which express HLADQ2 and HLADQ8 present this gliadin-tissue transglutaminase complex to T cells which then stimulate B cells to produce antibodies against both gliadin and TTG [85]. Typical symptoms of celiac disease are frequently absent in elderly which leads to diagnostic delay, increasing morbidity in this age group [86]. Evidence suggests increasing incidence of celiac disease in older adults in North America as seen in Olmsted County, Minnesota, USA, with 15.1 new cases per 100.000 in 2000-2001 compared to zero in 1950-1559 [87]. While some of these cases might be diagnosed in elderly for the first time due to diagnostic delay, there is evidence that celiac disease can truly occur for the first time in elderly in spite of long tolerance to gluten in the past [88]. As is typical in many autoimmune diseases, it is typically more frequent in females, yet we see that after age 65 incidence in women starts decreasing while it gradually increases in men [87]. It is unclear why gastrointestinal symptoms are less prominent in elderly patients with celiac disease, and the first sign of disease can be micronutrient deficiency [89]. Iron-deficiency anemia is present in up to 80% of elderly patients with celiac disease [90]. When abdominal symptoms are present in these patients, they are usually vague and nonspecific, manifesting as bloating, increased flatulence, and abdominal discomfort [83, 89].

Calcium and vitamin D deficiency are frequently found in celiac disease, which leads to metabolic bone disease and increased risk of fractures, especially with falls occurring at an older age. Liver involvement in celiac disease, seen in up to 20% of patients, is termed celiac hepatitis and usually presents as hypoalbuminemia, ascites, and abnormal liver function tests [91, 92]. Interestingly, celiac hepatitis is not auto-immune mediated disease unlike cholestatic liver diseases like primary biliary cholangitis, primary sclerosing cholangitis, and auto-immune hepatitis, which are also more common in people who have celiac disease [85]. Unlike celiac hepatitis, which usually resolves with gluten free diet, cholestatic liver disorders respond less favorably on gluten cessation.

Neurologic manifestation of celiac disease, particularly dementia, ataxia, and neuropathy, are especially difficult to diagnose in older adults due to the broad differential diagnosis and unfamiliarity amongst providers that celiac disease can present with neurological manifestations. This age group will frequently be misdiagnosed with Alzheimer or vascular dementia or gait instability due to age and deconditioning when, in fact, they may have atypical celiac disease. Apart from celiac disease, malabsorption syndrome in elderly might also be due to small bowel ischemia, bacterial overgrowth, and exocrine pancreatic insufficiency which makes diagnosis of celiac disease in these groups of patient with steatorrhea even more challenging.

While the diagnostic algorithm of celiac disease in elderly is the same as in younger groups, management can be particularly challenging since these patients can find complying with a strict gluten free diet more difficult. Some of this difficulty connects to residing in assisted living facilities, inability to precisely read ingredients while shopping, and finding lifelong habits difficult to break [85].

Mesenteric ischemia results from occlusion of celiac axis arterial branches and can be either acute or chronic. Its pathophysiology is related to either arterial occlusion by embolus (superior mesenteric artery affected in more than 50% of cases), gradual development of thrombosis secondary to advanced atherosclerosis, or hypo-perfusion secondary to hypovolemia and hypotension. Historically, embolic pathophysiology was a more common cause of acute mesenteric ischemia (AMI), yet more recent trends indicate atherosclerotic etiology is now more prevalent [93]. This may be due to increased life expectancy and population of elderly who more commonly have severe atherosclerotic changes as well as increased use of anticoagulation which will decrease embolic phenomena. Elderly are disproportionally affected by nonocclusive mesenteric ischemia related to states of hypo-perfusion such as during cardiopulmonary bypass surgeries, dehydration, hypovolemia, sepsis, and states of shock. Additionally, splanchnic blood flow decreases with age, making elderly more vulnerable to this type of hemodynamic injury. Chronic mesenteric ischemia (CMI) in elderly classically presents as post prandial angina leading to decrease in food intake and subsequent weight loss. Abdominal pain, which is a hallmark of presentation of acute mesenteric ischemia, in elderly is frequently absent or minimal and vague [94]. In contrast, CMI frequently presents with tachypnea, confusion, vomiting, and diarrhea. The onset of symptoms is usually insidious and when combined with ambiguity of symptoms makes establishing the correct diagnosis extremely difficult. A textbook definition of poorly localized abdominal pain out of proportion to the physical findings applies only to acute embolic mesenteric occlusion of a previously patent artery and is rarely seen nowadays.

Acute mesenteric ischemia is a more common abdominal emergency than ruptured abdominal aneurysm [95] and, in people older than 75, is a more common cause of acute abdomen than appendicitis. Elderly patients who have symptomatic chronic mesenteric ischemia are at very high risk of developing acute on chronic mesenteric ischemia. In fact, one study demonstrated that up to 80% of patients who developed acute on chronic mesenteric ischemia had been evaluated for similar complaints within 6 months before acute ischemia developed [96]. Diagnosis of AMI should be based on a combination of clinical suspicion (look for risk factors like peripheral arterial disease, atrial fibrillation, prior myocardial infarct, or stroke), laboratory findings (leukocytosis, elevated lactic acid, and metabolic acidosis) and radiological findings (thrombus in the artery, increased bowel enhancement, pneumatosis, etc.). Sensitivity of CT is variable, especially early in the disease, and can be increased in the setting of high clinical suspicion. In study by Karkkainen only 50% of patients with documented bowel ischemia had CT findings of thrombus in the artery [93]. Studies by Schermerhon and Arthus showed that endovascular therapy is associated with lower mortality when compared to open revascularization (16% vs 28%) [97, 98] and is preferable in elderly who usually have a plethora of other co-morbidities making them poor candidates for open surgery.

Small bowel bleeding (SBB) makes up only 5% of GI bleeds, yet it is the most common cause of obscure GI bleeding. The small bowel is defined as the region between the ligament of Treitz and the ileocecal valve. It is called “the dark continent of the GI tract” due to its excess mobility, long length, and relative inaccessibility to endoscopy. Unlike for young adults in whom intestinal tumors and Crohn’s disease are the most common causes of small bowel bleeding, vascular anomalies, small intestinal ulcers, and NSAID enteropathy are the most common etiologies in elderly populations [99]. A study by Zhang et al. [100] found that 54% of small bowel bleeding in elderly patients was due to angiodysplasia.

Angiodysplasias are acquired lesions associated with aging. They are characterized by the presence of a cluster of dilated, torturous, thin-walled vessels involving small capillaries, veins, and arteries [101]. The increase in incidence of angiodysplasia with age is thought to be due to changes in the composition and structure of extracellular matrix in the wall of the small intestine. They are associated with Heyde’s syndrome, a well described clinical syndrome of bleeding from angiodysplasia in patients with aortic stenosis, which incidence increases with increasing age [102]. Another condition associated with increased frequency of GI angiodysplasia is chronic renal failure. Study by Karagiannis et al. found that 47% of patients with chronic renal failure had small bowel angiodysplasia compared to 17.6% in people with normal renal function [103]. Apart from patients with aortic stenosis and chronic renal failure, newly recognized risk factors associated with presence of small bowel angiodysplasia include female gender, chronic respiratory condition, VTE, and use of warfarin [104].

Small bowel ulcers are another common cause of SBB in elderly. Interestingly, one study from India found small bowel ulcers to be a more common cause of obscure GI bleed than angiodysplasia [105]. While Crohn’s disease ulcers are more common in young adults, NSAID-associated small bowel ulcers are the most common cause in elderly. The prevalence of small bowel ulcers increases with age. When compared to young adults (below 40) who have a 7.27% incidence of small bowel ulcers, elderly (above 65) have an almost double incidence of 13.04% [100].

Finally, elderly patients who are more likely to have abdominal aortic aneurysm and undergo surgical or endoscopic repair are at high risk for development of aorto-enteric fistulas which are another important but uncommon cause of SBB in elderly [106]. Unlike bleeding from angiodysplasia that is usually slow and recurrent, this type of bleeding is usually massive and life-threatening with high mortality in elderly.

A study by Compagna et al. found that most elderly patients treated with either argon plasma coagulation(APC) or bipolar electrocoagulation(BEC) achieved good hemostasis after the first cycle. They also found that recurrence of bleed was lower in patients who were treated with APC (10%) in comparison to those treated with BEC (20%). Overall they concluded that elderly showed good response to endoscopic treatment [107].

Small intestinal bacterial overgrowth (SIBO) implies excessive presence of bacteria, above 10 5 -10 6 organism/mL in small bowel aspirate [108]. Common in elderly it is associated with chronic diarrhea, malabsorption, weight loss, and secondary nutritional deficiencies. Prevalence of SIBO in the healthy population is significantly higher among elderly when compared to younger adults, 15.6% vs 5.9% [51]. The prevalence of SIBO in healthy elderly adults in UK was found to be 14.5% [109]. Interestingly a study from Japan that included healthy elderly (mean age 74 years) found no patients with SIBO [110]. It seems that exact prevalence of SIBO varies between the countries and geographic location. It is higher among elderly, especially those hospitalized or in long term care facilities. Several factors contribute to the development of SIBO such as achlorhydria, small intestinal dysmotility, increased transit time, alteration in gut immune function, and anatomical abnormalities (bowel resection, presence of anastomosis, and fistulas). Among these, the two primary factors associated with risk of SIBO are achlorhydria and small bowel dysmotility, both of which are more common in elderly [111]. Achlorhydria, as previously mentioned, is associated with use of medications such as PPIs and H2 blockers as well as the presence of H.pylori infection. Decrease in gastric acid production allows bacteria to pass through the stomach and overpopulate the small intestine. The risk of SIBO appears to be higher in patients treated with PPIs than H2 blockers. Gastroparesis with impaired gastric transit time and delayed gastric emptying can increase risk of SIBO due to food and bacterial stasis in the upper gastrointestinal tract. Small bowel motility disorders predispose patients to SIBO because bacteria are not effectively swept distally to colon. Patients with diabetes, portal hypertension, chronic renal failure, scleroderma, and polymyositis have higher risk of development of SIBO in comparison to healthy patients [112, 113].

Motility of the small intestine is not affected by age itself. Rather than age itself, slower motility in elderly is associated with medications, polypharmacy, and presence of concomitant diseases more frequently seen in this population such as autonomic neuropathy from long standing diabetes. Clinical manifestation of SIBO can typically include nausea, vomiting, and diarrhea [108]. In the elderly, these may be not as prominent and manifestations of the disease can be more subtle and include nonspecific abdominal distention, bloating, and poorly localized discomfort may mimic other diseases such as irritable bowel syndrome, celiac disease, lactose intolerance, fructose intolerance, or inflammatory bowel disease. Symptoms of SIBO complications due to malabsorption, such as vitamin and mineral deficiencies, might be the first sign in elderly. Unlike vitamin B12 deficiency that is commonly seen in SIBO due to competitive uptake of vitamin B12 by bacteria, vitamin K and folic acid are usually normal in patients with SIBO since they are produced by gut bacteria. Diagnosis of SIBO is similar to young adults and includes small bowel content aspiration and, more commonly, glucose or lactulose breath tests [108]. Treatment includes dietary changes emphasizing low carbohydrate diet, increasing GI motility by use of prokinetic agents, and reduction of bacterial overgrowth using antibiotics. Due to frequent presence of polypharmacy and medication interactions, use of prokinetic agents is especially challenging in elderly populations. Additionally, use of antibiotics is associated with development of CDC which carries high morbidity and mortality in this age group. Hence, the risk and benefits of using antibiotics and prokinetic agents should be weighed on and individual basis in elderly. Table 4 summarize small intestine diseases in elderly.

6. Large Intestine

Several studies tried to address whether the process of aging itself negatively impacts gastrointestinal motility and increases colon transit time. The results from these studies yielded conflicting results and at this point it remains unclear whether or not age itself is a risk factor for development of motility disorders of the large intestine. Metcalf et al. found that aging itself doesn’t influence colon transit time, while Madsen and Graf found the opposite—increased colon transit time in people age 80 and above [42, 114]. Despite these discordant observations, most experts agree that constipation is not a physiologic consequence of normal aging. In fact, most healthy older people have normal bowel function. If some degree of motility impairment due to age is present, it might be related to decreased ability of enteric smooth muscles to contract and relax or to changes in enteric nervous system and reduction in the concentration of neurotransmitters [50, 115]. Hanani et al. documented observations that the myenteric plexus of the human colon undergoes changes with aging that manifest as increases in cavities of myenteric neurons [116]. On the other hand, Bernard and colleagues found that neuronal loss in the myenteric plexus was specific to cholinergic neurons while nitrinergic neurons were spared [117]. Decreasing synthesis of neurotransmitters is another theory that attempted to explain potential decrease in colon transit time associated with aging and Takahashi et al. documented a significant decrease in nitric oxide synthase (NOS)-immunoreactive cells as well as NOS synthesis in colonic neurons [118]. In contrast to the above findings, a study by Southwell et al. found that healthy elderly people do not have significant reduction in numbers of submucosal myenteric neurons [119]. While we are awaiting further studies to clarify these conflicting results, it seems that age-related changes in the colon are clinically insignificant in the absence of other conditions that predispose elderly to decreased colon transit time and constipation such as anticholinergic medications, decrease in mobility, dietary changes, and comorbid medical conditions.

Another important change that occurs along the process of aging is the change in human intestinal microbiota [120]. There is a high degree of variability between infant microbiota (dominated by Bifidobacterium) and microbiota of an adult person (Bacteroidetes and Firmicutes dominate). Age-related changes in human microbiota have been associated with inflammatory bowel diseases (Crohn’s disease and ulcerative colitis), irritable bowel syndrome, and metabolic disorders (diabetes mellitus types 1 and 2 and obesity). Two major phyla of human microbiota are Firmicutes (gram positive bacteria) and Bacteroidetes (gram negative bacteria) [120]. Immune homeostasis by intestinal microbiota is maintained by the equilibrium between these two major phyla. Age-related alteration in this balance may lead to activation of dendritic cells within the lamina propria of the intestine which, in turn, starts the cascade of events leading to release of pro-inflammatory cytokines, mainly interleukins 6 and 17. These alterations further lead to decreased secretion of mucus and α-defensins by intestinal epithelial cells (IEC), which then allows entry of pathogens into mucosal layers, finally resulting in generation of low grade inflammation, “inflamm-ageing” [121]. Short chain fatty acids (SCFA) produced by healthy microbiota have anti-inflammatory and antineoplastic properties. In elderly, age-related alteration of microbiota leads to decrease in production of SCFA which may promote inflammation as well as decrease function of IECs [122].

Constipation is defined by most clinicians as a decrease in defecation frequency to three or fewer per week and Rome criteria are the most frequently used consensus definitions clinically and for research [123]. The estimated prevalence of constipation in the general population is reported to be anywhere from 2%-28% [124]. In elderly, this number goes up to 40% [125] and up to 50% of elderly nursing home residents [126]. Constipation is also more common in females, African Americans, and persons from lower socioeconomic status [127]. Increase in prevalence of constipation in elderly is not related to decrease in colon transition time as much as it is to decreased mobility, cognitive impairment, comorbid medical problems, polypharmacy (especially opioid and anticholinergic medication use), and dietary changes. Elderly patients usually associate constipation with straining rather than decreased frequency of bowel movements. Primary constipation can be divided in three groups: (1) normal transit constipation (2) slow transit constipation and (3) anorectal dysfunction. The most common among these is normal transit constipation which is also called functional constipation. Anorectal constipation might be secondary to age-related changes in anorectal physiology including increased rectal compliance, impaired rectal sensation, and impaired defecation [128]. In this type of constipation, inefficient coordination between pelvic musculature and evacuation mechanism often occurs. Physiologic changes that contribute to constipation in elderly have less to do with increased colonic transit time and more with anorectal function changes. There is a significant overlap between normal transit constipation and irritable bowel syndrome (IBS), with the main clinical difference between these two being predominance of abdominal pain and discomfort among elderly with IBS [129]. Secondary constipation is either due to medication side effect (calcium channel blockers, opioids, NSAIDs, iron pills, antacids) or associated with countless other diseases including endocrine (hypothyroidism, hypercalcemia), neurologic (Parkinson’s disease, neurogenic bowel due to spinal cord injury, stroke), rheumatologic (scleroderma, amyloidosis) and psychological (somatization,depression). A major and most feared complication of constipation in elderly is stool impaction, which can lead to stercoral ulcerations and colonic perforation which carry high mortalities in elderly populations. Fecal impaction refers to accumulation of hardened feces in the rectum or colon which causes diminished rectal sensation and subsequent fecal incontinence [128]. Symptoms of fecal impactions are constipation associated with abdominal pain, urinary symptoms, respiratory distress, and even fever in severe cases. Liquid stool from the proximal colon can bypass the impacted stool causing paradoxical diarrhea, so the presence of diarrhea alone cannot exclude fecal impaction.

Diverticular disease (DD) is a term used to describe two conditions: diverticulosis and diverticulitis. Combined, they are the most common disease affecting the large bowel in the Western world, with the highest rates in the Unites States and Europe showing no gender predilection [130]. The prevalence of DD has increased over the past decades throughout the world and while it can affect any adult patient, the prevalence increases with age [131]. DD is uncommon in those under age of 40 with estimated prevalence of 5% and quite common by age 80 with an approximate prevalence of 70% in the US [130–132]. Diverticulosis is an acquired condition referring to presence of diverticula—sac like outpouchings of mucosa and submucosa of colonic wall. They are believed to develop due to increased intraluminal colonic pressure at the points of least resistance in the muscular wall where vasa recta insert. While it is primarily a left colon disease in people from Western societies largely affecting the sigmoid and descending colon in 90%, in Asians it mostly often affects the right side with the cecum and ascending colon being affected in 55%-71% [133, 134]. The importance of a genetic component in the occurrence and location of DD is exemplified in the fact that in the Japanese Hawaiian community, the dominant site of DD occurrence has remained on the right side as it has in the indigenous Japanese population [135].

Diverticulitis is considered the most common complication of diverticulosis and refers to inflammation of diverticula that can vary in severity and is associated with its own complications such as bleeding, micro-perforation, abscess formation, and/or secondary bacterial peritonitis. Diverticular colitis represents intense inflammation of colonic mucosa in and around areas of multiple diverticula manifested as abdominal pain, change in bowel habits, and hematochezia [136].

A growing body of evidence is shifting the paradigm of diverticular disease from being an acute surgical disease to a chronic bowel disorder composed of recurrent flares with intervals in between filled with either relatively asymptomatic times or vague and recurrent abdominal discomfort [136]. These relatively milder symptoms in periods between the flares might mimic other gastrointestinal disorders, such as irritable bowel syndrome (IBS). It is unclear whether ongoing mild symptoms after an episode of diverticulitis flare result from ongoing low grade inflammation that continues after acute symptoms resolve or from previously unrecognized IBS. It can be possible that an episode of diverticulitis exacerbates or/and triggers IBS similar to already described post infectious IBS. Hence, DD presents with the spectrum from asymptomatic presence of diverticulosis to symptomatic uncomplicated diverticular disease to, finally, complicated disease [130]. Pathophysiology of DD is linked to age-related changes in the connective tissue of the colonic wall which include an increase in collagen crosslinking and increased elastin content both leading to increased colonic wall rigidity [137]. Additionally, it incorporates a complex interplay between colon microbiota, inflammation, visceral hypersensitivity, and colonic motility [136].

The natural history of diverticulitis is poorly understood and research on this topic has been lacking. Traditionally it is believed that among those with diverticulosis, about 25% will go on to develop the most common complication—diverticulitis [138]. More recent studies, however, described the incidence of diverticulitis to be as low as 1-2% among those with diverticulosis [139, 140]. A study by Strate et al. found an overall incidence of less than 5% contrary to previously held dogma that 25% of patients with diverticulosis will develop diverticulitis in their lifetime [136]. When they applied the stricter criteria for the diagnosis of inflammation, including CT documented disease, this incidence further decreased to 1%. Interestingly they noted that younger patients, in comparison to elderly, had significantly higher incidence of diverticulitis per year suggesting that younger age may be a risk factor for development of diverticulitis. Additionally, diverticulitis developing in younger patients more often becomes complicated [130, 136]. Hogan et al. [141], in their series of 930 patients with diverticulosis but without diverticulitis, found that 75% had evidence of inflammation in and around diverticula. It led some authors to propose that diverticulosis might be either a milder form of inflammatory bowel disease (IBD) or tightly connected to it [142]. It further led to exploring of use of mesalamine in the treatment and prevention of diverticulosis and diverticulitis, respectively. Connecting to the idea that imbalance in colonic microbiota may be responsible for the development of diverticulosis and its complications, there are ongoing studies investigating use of rifaximine, alone or in combination with mesalamine, for treatment and prevention of DD [143, 144].

While some medications commonly used by elderly (such as NSAIDS, steroids and opioids) are linked with an increase in the risk for DD [145, 146], others like calcium channel blockers and statins showed protective effect [147]. Hence, it would be reasonable to use calcium channel blockers as first line antihypertensive in patients with concomitant hypertension and DD in the absence of stronger indications for other comorbidities (for example beta blockers in known coronary artery disease or angiotensin converting enzyme blockers in patients with diabetes and hypertension). Elderly people with diverticulosis are at increased risk of ischemic colitis which, unlike diverticulosis which usually presents as painless hematochezia, is usually associated with abdominal pain and elevation in lactic acid. It appears that elderly patients with atherosclerosis are more prone to develop diverticular bleeding then controls without atherosclerotic diseases [132].

Studies from UK demonstrated that patients with DD have lower health related quality of life [148]. Even patients with uncomplicated diverticulosis have lower quality of life when compared with unaffected age and sex matched controls [149].

Following resolution of an episode of diverticulitis, it has been a standard of care to have a colonoscopy to rule out underlying malignancy mimicking diverticulitis. A recent retrospective study and systematic review, however, showed that incidence of malignancy in these cases is truly low [150]. Hence, follow up colonoscopy might need to be limited to those with persistent symptoms, alarm findings, or suspicious CT findings.

Irritable bowel syndrome (IBS) is common functional gastrointestinal disorder. It manifests with abdominal pain and alteration in bowel movements in the absence of any organic pathology [151]. Symptom-based criteria known as Rome criteria are the most widely accepted method of diagnosing IBS since there is no pathognomonic result or finding [152]. Depending on bowel patterns, IBS can be diarrhea predominant, constipation predominant or IBS with mixed bowel habits. The prevalence of IBS seems to be similar in elderly and younger people [153], yet the incidence of IBS is highest in adolescence and is rarely diagnosed for the first time after age 65. While IBS symptoms are not significantly different across age groups, elderly are more likely to have organic gastrointestinal disease, hence, a careful diagnostic approach should be used in this particular group. Clinicians who provide care for elderly frequently encounter patients who have multiple GI complains, take various medications that might affect GI system, and have a plethora of other co-morbidities. Taking all these factors into account, it is difficult to confidently diagnose IBS in such circumstances. In fact, a prospective study, done on sample of 230 patients visiting elderly care clinic in the UK found that a striking minority (only one patient) with IBS was actually diagnosed with the disease, despite 22% having symptoms suggestive of IBS [154]. It seems that clinicians are more likely to attribute GI symptoms in elderly to an organic or medication-related etiology than to a functional disorder. Traditional approaches that argue for minimal investigation once IBS is suspected are plausible in younger people without alarm features, especially if accompanied with psychological disorders of anxiety, depression or somatization. In elderly, however, who are more likely to have alarm features, this approach is not realistic and IBS should be a diagnosis of exclusion in the appropriate clinical setting. Rectal bleeding is considered an alarm feature but is frequently found in patients with IBS of any age [155], whereas weight loss and poor appetite are “red flag symptoms” that are commonly found in elderly irrespective of the presence of IBS. In elderly male patients, chronic prostatitis can mimic IBS and present as intermittent diarrhea, passage of mucus, abdominal pain, and difficulties in evacuation. Pathophysiology of IBS is not clear and multiple theories such as altered gut motility, visceral hypersensitivity, psychosocial theory, altered gut microbiota, and post infectious have been proposed [156]. These are similar to theories about pathogenesis of diverticulitis. One recent theory argues that gut motility affected by 5-HT (serotonin) concentration might be responsible for IBS [157, 158]. In fact, we know that serotonin is a mediator in initiating colonic motility and increased serotonin concentrations have been found in diarrhea predominant IBS while patients with constipation predominant IBS were more likely to have lower concentrations of serotonin. IBS treatment is the same across different age groups, yet medication side effects and polypharmacy can lead to cautious use in older adults. Patients treated with selective serotonin reuptake inhibitors had significantly higher response and improvement in their IBS symptoms when compared to the group treated with tricyclic antidepressants (TCA) [159]. TCA and antispasmodic medications can exacerbate urinary retention, closed angle glaucoma, and cognitive impairment in elderly secondary to their anticholinergic properties. Among nonpharmacological therapies, CBT seems to be associated with the best results.

Clostridium difficile colitis (CDC) is a major cause of GI infection worldwide and occurs in adults aged 65 and above in up to 80% of cases [160]. Elderly populations are particularly vulnerable to this infection and suffer higher morbidity and mortality when compared to younger counterparts [161]. CDC occurs due to dysregulation of gut microbiota and most commonly is due to use of antimicrobials [162]. The virulence factors of C. difficile are toxin A and toxin B, which exhibit their pathologic effect by damaging colon epithelium and generating an acute neutrophil predominant inflammatory response resulting in the hallmark macroscopic manifestation of CDC—formation of pseudomembranes.

Clinical manifestation varies and includes mild diarrhea, moderate disease accompanied by dehydration and acute kidney injury, and severe life threatening disease with toxic megacolon accompanied by sepsis and septic shock [163]. The most severe forms of the disease disproportionally affect elderly people, nursing home residents, and malnourished patients [137]. The incidence of CDC has dramatically increased over the last few years, with rates tripling in the Unites States and Canada [164]. CDC hospitalization rates are significantly higher in those of age 65 and above (by fourfold) and especially those older than 85 (by tenfold) when compared to groups younger than 65 [165]. Not only did the incidence of CDC increase, but mortality did as well, from 5.7 deaths per million in 1999 to 23.7 in 2004, despite significant advancement in our knowledge about preventive measures, early recognition of infection, and appropriate treatment [166]. This increase in mortality is mostly driven by the emergence of more virulent strain of bacterium called NAP-1 (North American pulsed –field 1/PCR ribosome 025] [167]. Increasing age and the use of fluoroquinolone are identified to be risk factors for infection with the NAP-1 strain [168]. A prospective cohort study from Canada identified age above 65, antibiotic exposure, and use of proton pump inhibitors to be significantly associated with health care associated CDC [169]. In addition to more severe forms of disease and risk for health care associated infection, age is also a risk factor for recurrent disease [170]. CDC recurrence can be predicted by the Hu prediction tool [171]. Three clinical factors emerged to be the most important for prediction of CDC recurrence: age above 65, fulminant or severe underlying co-morbidities, and additional antimicrobial use following initial treatment for CDC. Aging is associated with alteration in important physiologic barriers to infection including immunosenescence, which is a complex age-related change in the immune system that makes elderly more susceptible to infections [172]. Immunoscenescence is directly related to decreases in T and B cell numbers and the decline in their immunologic function [173]. A particularly important step in the pathogenesis of severe CDC in elderly is a decrease in diversity of GI microbiome associated with aging [174], which contributes to dysregulation of gut microbiota and predisposes older individuals to development of CDC. Decreased functional status is also an independent risk factor for poor outcome in older adults [137].

Treatment of CDC includes discontinuation of the precipitating antimicrobial whenever possible, IV hydration, and initiation of anti C. difficile antibiotics. While initial studies demonstrated equal effectiveness of metronidazole and vancomycin, several new studies showed superiority of vancomycin over metronidazole in elderly people with severe disease [175–177]. Increased treatment failure in the older adults was associated with metronidazole therapy in a systematic review by Vardakas [175]. These and a few other observations lead the Infectious Disease Society of America (IDSA) to recommend Vancomycin as initial empiric therapy in the newest guideline from 2018 [178]. Metronidazole is systemically absorbed and may cause side effects such as nausea, dysgeusia, seizures, peripheral neuropathy or encephalopathy. Vancomycin and fidaxomicin, on the other hand, are not systemically reabsorbed leading to a better side effect profile, which is especially important in the elderly who are frequently on multiple other medications. Fecal microbiota transplant (FMT) has emerged as effective treatment for recurrent C. difficile infection who failed multiple antibiotic treatments. FMT, similar to other treatment options, is also associated with higher overall recurrence rate among older groups (9.3%) compared to younger populations (4.6%) [179]. Additionally, due to age-related changes in gut microbiota and diversity of microbiome, elderly do not appear to be ideal stool donors. A study by Anand et al., however, did not demonstrate significant difference in alfa diversity between groups above and below age of 60 [180].

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the GI system which encompasses two main types: Crohn’s disease (CD) and ulcerative colitis (UC) [181]. Elderly patients with IBD are defined as patients above age of 60 and includes both those who developed disease at a younger age and transitioned to older age and those who developed the disease or are diagnosed for the first time after the age of 60 [182, 183]. For a long time, it was believed that IBD is a disease of young people, yet the prevalence of IBD in patients above 60 is 10-30% [182]. Up to 15% of newly diagnosed patients in the US are elderly, although, the incidence is probably underestimated due to challenges diagnosing this disease in the elderly [184]. Older adult onset UC is more common than CD [185, 186]. The incidence rate of IBD is higher in the US when compared to Asia [185–187], although the incidence is on the rise in Asian countries. It is expected that the prevalence of IBD in elderly will significantly increase due to its relatively low mortality and the fact that majority of those diagnosed at younger age will transition to elderly.

IBD arises in genetically predisposed individuals who develop an abnormal immune response to different gut antigens and their by-products. Genetics seems to be less responsible in the development of IBD in elderly population when compared to those diagnosed at younger age. In fact, 16% of patients younger than 17 who are diagnosed with CD have a family history of IBD, compared to only 7% elderly patients [183]. Apart from a decline in the number and function of T and B lymphocytes, age-related immunosenescense is associated with changes in intestinal microbiota increasing the risk for aberrancy of the immune system and developing IBD [120, 188–190]. As previously mentioned, establishing the diagnosis of IBD in the elderly is difficult. Atypical presentation of IBD, presence of multiple co-morbidities, and polypharmacy affecting bowel function all contribute to challenges in establishing the diagnosis. When compared to their younger counterparts, elderly tend to present with isolated colonic inflammation and perianal fistulas. Less frequently they have small bowel disease or upper gastrointestinal tract involvement [183, 187]. Rectal bleeding is more common than diarrhea, abdominal pain, and weight loss in older onset CD. Older onset disease is more frequently associated with inflammatory phenotype unlike younger patients in whom structural and penetrating disease predominates [182]. On the other hand, older onset UC tends to present with more left colon disease, proctitis, and rectal bleeding with abdominal pain being less pronounced [183, 187]. Older onset IBD may be associated with less inflammation, fewer signs of disease, and less progression of disease. A French cohort study found that 92% of older onset CD did not progress over a period of 2 years and only 3-5% of older onset UC patients progressed to extensive disease [183].

IBD treatment aims to induce and maintain remission, prevent and minimize disease related complication, and improve quality of life. It can be particularly challenging in elderly due to polypharmacy and the presence of multiple medical co-morbidities. Additionally, elderly patients have often been excluded from clinical trials, especially ones including immunosuppressive therapy. Mesalamine is first line therapy for mild to moderate disease and is prescribed in 84% of elderly with UC [183]. Topical mesalamine treats disease involving the last 10 cm of rectum and enemas can potentially address disease up to the splenic flexure [191]. In elderly UC patients with proctitis, a combination of oral and topical mesalamine is more effective than either treatment alone. The rates of nonadherence to mesalamine among elderly is 40-60% [192] and are related to pill size, frequency of dosing, and common side effects such as nausea, vomiting, and abdominal pain. Additionally, use of mesalamine in elderly is difficult due to higher prevalence of CKD among elderly who are more likely to develop nephrotoxicity from mesalamine than younger patients and higher rates of fecal incontinence in this age group, limiting the use of suppository forms. Corticosteroids are very effective in establishing, but not maintaining, the remission in moderate to severe IBD [170]. The use is associated with an increased risk of development and/or worsening of osteoporosis, diabetes mellitus, glaucoma, and hypertension, which are all particularly prevalent in older populations. Risk of hip fracture associated with use of corticosteroids is the highest in those above 60. Despite having the same efficacy in elderly as in younger people, immune-modifying agents are underutilized. A retrospective study of IBD patients above age of 65 found that only 6% of them were on 6-mercaptopurine (6-MP) and just 1% on methotrexate [190]. The potential of immune modifying agents to cause adverse events is not increased in elderly when compared to younger patients [193]. The studies on anti-TNF therapy in elderly are conflicting. A study from Italy compared clinical remission rates among those older than 65 with younger counterparts on anti TNF therapy and found that remission rates were 59% in older UC patients and 65% in older CD patients, which were similar to rates in younger adults [194]. A retrospective study from the US, however, found lower response among elderly who were also more likely to stop therapy [195]. The risk of infection appears to be 12% among elderly on anti-TNF therapy [196]. Live active vaccines are generally contraindicated in immunocompromised patients, including those treated with anti-TNF therapy. Interestingly, recent studies showed that live attenuated herpes zoster vaccine may be safe in some elderly with IBD and should be assessed on a case-by-case basis [196]. Table 5 summarize disease of large intestine in elderly.


Conclusions

Neural activation is a better option than muscular activation because it is a more physiologic way to activate or induce transit in GI organs and it requires lower power consumption. However, muscular activation can be performed when neural systems are either inactive, destroyed, or do not respond properly to electrical stimulation.

Although the basic mechanisms supporting and controlling propulsion are similar along the GI tract, differences in their responsiveness to electrical stimulation exist, not only between the GI organs, but also between different regions of the same organ. Because of this, parameters of stimulation should be tailored to the functional characteristics of the regions stimulated.

The GI tract is not a system of independent organs but a unitary system of interacting organs. Changing the functioning parameters of one GI segment will most certainly affect other GI segments and this may, in fact, disturb the physiology of the digestive system as a whole. Moreover, due to the common extrinsic innervation and hormonal interactions between GI segments, stimulation of one GI segment may affect the functioning of other GI segments. The possibility that electrical stimulation may induce undesirable side-effects must be studied further.


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