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Diarrhoea and aging. RN RatnaikeDepartment of Medicine, The Queen Elizabeth Hospital, Woodville, Australia. , Australia
Correspondence Address: Source of Support: None, Conflict of Interest: None PMID: 0010734337 Keywords: Aged, Aging, immunology,physiology,Diarrhea, etiology,physiopathology,Human,
Diarrhoea is a common illness of diverse aetiology in the elderly. Because of physiological heterogeneity, the elderly are not at equal risk of acquiring diarrhoea, but compared to younger persons are more susceptible[1],[2]. In the elderly the likelihood of diarrhoea increases due to diminished physiological reserves, the burden of acute or chronic multisystem illnesses, under-nutrition, general debility and cognitive impairment. Diarrhoea is also relevant to the elderly as it is an important cause of morbidity and potential mortality. The frequency and severity of dehydration and electrolyte loss, which may cause death increases in the elderly[3] and even a short episode of diarrhoea may result in severe nutritional deficiencies[4]. Diverse factors predispose the elderly to diarrhoea. The aging process influences physiological homeostatic mechanisms increasing vulnerability to enteric pathogens[5]. Some systemic diseases more common in the elderly directly involve the gastrointestinal tract and cause diarrhoea. A prominent cause of diarrhoea is gatrogenic due to radiation therapy, and surgery on the gastrointestinal tract though the most common is drug therapy[6]. The elderly are at an increased risk of diarrhoea from nosocomial due to institutionalisation, and admissions to acute hospitals associated with a longer length of stay[7],[8].
Aging causes a decline in the systemic humoral and cellular immunological responses contributing to enteric infections. Loss of T cell numbers and alteration in the proportion of T-helper and T-suppressor sub populations and their qualitative changes are specially relevant[9],[10]. The primary immune response at the intestinal interface is the production of secretory immunoglobulin A (sIgA) by B cells of the lamina propria. B cell maturation to become IgA secreting cells is in turn highly T cell (particularly T4) dependent[11] Secretory IgA synthesised in the small intestine prevents enteric pathogens from adhering to the intestinal mucosa[12],[13]. Aging results in a loss of follicles in Peyer's patches[14], the site of antigen sampling, generation of tolerance and, or immunisation primarily in the form of a secretory antibody response[15]. The immune responses are further weakened by drug therapy in malignant disease, which are increased in the elderly[16]. The side effects of immunosuppressive drugs especially when used with corticosteroids in high doses, include impaired cell renewal integral for efficient host defences. Immune responses are also weakened by malnutrition reported in up to six percent of elderly patients in one study[17].
The aging process also influences the non-immunological defences of the gastrointestinal tract, the gastric acid barrier[18],[19], the motility of the small intestine[20] and the commensal flora of the colon[21]. The gastric acid barrier Gastric acid is essential to prevent the colonisation of the upper gastrointestinal tract by viral, bacterial and protozoan pathogens. In the stomach the pH is usually below 4 and prevents the survival of pathogens which may cause diarrhoea[22],[23] Up to 80 per cent of healthy elderly subjects (mean age of 84 years, range 80-91 years) are reported to be hypochlorhydric with gastric bacterial colonisation[24] The traditional view that gastric acid production decreases with age[25],[26] has been challenged by Hurwitz et al[27] and needs to be confirmed. Decreased acid production significantly increases the risk of diarrhoea in immunocompromised patients[19]. Conditions more common in the elderly such as pernicious anaemia and chronic atrophy gastritis contribute to decreased gastric acidity[28] In both peptic ulcer, which is more prevalent with advancing years[29] and in the Zollinger-Ellison syndrome, in which one third of patients are over 60 years[30], the therapeutic goal is to decrease gastric acid production or increase pH. Cimetidine an H-2 receptor blocker, causes diarrhoea in 3 per cent to 12 per cent of patients[31],[32] and is a significant risk factor for carriage of Clostridium difficile  h the potential to develop pseudomembraneous colitis[33]. Omeprazole the powerful proton pump inhibits resulted in bacterial overgrowth which can lead to diarrhoea in 53 per cent of patients[34]. Disorders of small intestinal motility Small bowel motility provides a cleansing action that sweeps away intestinal pathogens and digested luminal contents to the colon and this function may be directly or indirectly compromised with age[20] The influence of age alone on motility requires further study[35],[36]. Diarrhoea may result from decreased motility which leads to small intestinal bacterial overgrowth. Decreased motility occurs with anti-cholinergic drugs, and compounds with anti-cholinergic properties used by the elderly in urinary incontinence to control uninhibited detrusor contractions[37],[38], in Parkinson's disease and depressive illnesses. Though these drugs may cause diarrhoea due to hypomotility and bacterial overgrowth, constipation is the predominant side-effect. Consequently spurious diarrhoea due to faecal impaction may result. Thyroid replacement in hypothyroidism and thyrotoxicosis are potential causes of hypermotility and diarrhoea[39],[40]. In Alzheimer's disease, due to its cholinergic action Tacrine, a cholinesterase inhibitor, causes diarrhoea, the most severe clinical side-effect[41],[42]. A new agent in treating colorectal cancer, irinotecan, causes severe diarrhoea, also due to a cholinergic like syndrome[43],[44]. Colonic commensal bacteria The third non-immunological line of defence is the remarkably stable commensal bacteria of the colon[21] and this line of defence is breached by antibiotics which are used more frequently in the elderly[45],[46]. The host friendly bacteria prevent new organisms from colonising the colon. They induce peristalsis; initiate immunologic responses; deplete essential substrates from the environment and create a restrictive environment[47]. Antibiotic associated diarrhoea, due to the temporary alteration of colonic bacteria is mild, and self-limiting[48]. However, superinfections occur frequently with C. difficile[49] and, rarely with C. perfringens[50], Salmonella More Details and Shigella[51]. Pseudomembraneous colitis due to C. difficile is the most serious consequence of antibiotic associated diarrhoea. Almost all antibiotics have been implicated including vancomycin and metronidazole used in treating C. difficile infection. Due to frequent use the commonest antibiotics implicated are lincomycin, clindamycin, cephalosporins, amoxycillin and ampicillin[52],[53]. C. difficile is responsive to oral vancomycin, bacitracin and metronidazole.
The elderly are at an increased risk of acquiring infectious diarrhoea due to additional predisposing and risk factors and include malnutrition, severe co-existing illnesses, cognitive impairment and physical infirmities that compromise personal hygiene, and domestic hygiene especially in regard to food preparation and storage. Aging predisposes to a unique and commom form of diarrhoea due to small bowel bacterial overgrowth (Blind loop syndrome, Stagnant loop syndrome). The cause is unknown[54],[55]. Malabsorption is a consequence[17]. Institutionalisation significantly increases the risk of infection from common source outbreaks such as food-borne epidemics and by person to person spread[56] Shared toilet facilities with patients with infective diarrhoea (especially those with faecal incontinence) increases the risk of infection[57] The hospital environment itself predisposes to C. difficile[58].
Disruption of the Na+-K+ exchange pump The aging process is associated with a decrease in Na+-K+ ATPase activity which is required to breakdown ATP to provide the energy for the Na+-K+ exchange pump which regulates water and electrolyte transport[59],[60]. Decrease in Na+-K+-ATPase concentrations reduces the activity of the Na+-K+ exchange pump resulting in decreased fluid absorption. In addition to age related changes of the Na+-K+ exchange pump, drugs decrease Na+-K+-ATPase concentrations and contribute to the decreased efficiency of the Na+-K+ exchange pump. Digoxin a drug widely used in the elderly is almost completely absorbed from the small intestine but small amounts reach the colon where it decreases Na+-K+-ATPase activity, and may cause diarrhoea[61]. Digoxin was the commonest cause of diarrhoea, second only to antibiotics in 100 elderly in-patients[62] and in another study caused diarrhoea in 41 per cent of patients[63]. Auranofin, an oral gold preparation used in rheumatoid arthritis and colchicine used in gout, causes diarrhoea by a concentration dependent inhibition of ATPase which decreases activity of the ileal and colonic Na+-K+ exchange pump[64],[65]. Secretory processes A number of drugs used in treating the illnesses more common in the elderly act to increase secretion of water and electrolytes in the small intestinal epithelial cells[66]. These compounds act as secretagogue to activate adenylate cyclase within the small intestinal enterocyte to increase the concentration of cAMP; which causes active secretion of Cl- (predominantly) and HCO3- by the crypt cells and decreased electroneutral Na+ and Cl by the more mature intestinal epithelial cells[67]. Net fluid excretion results in diarrhoea. Examples of drugs, which act as secretagogues are bisacodyl[68] and misoprostil. The incidence of gallstones increases with age[69] and chenodeoxycholic acid, a primary bile acid, is widely used in their dissolution. Due to increased cAMP in the colon causing net fluid secretion[70] diarrhoea occurs in upto 49 per cent of patients[71]. Intestinal mucosal damage Another mechanism by which drugs used by the elderly cause diarrhoea is damage to the small and large intestinal mucosa. Colchicine in addition to mechanisms previously mentioned also causes diarrhoea due to malabsorption secondary to patchy partial villous atrophy or even sub-total villous atrophy[72]. Colitis may occur with the use of auranofin; non-steroidal anti-inflammatory agents; with cancer chemotherapeutic agents such as 5-fluouracil, penicillamine, and with methyldopa (though now less commonly used in hypertension)[73].
Drug treatment Examples of drugs used in acute and chronic illnesses of old age associated with diarrhoea have been discussed in this review and in greater detail elsewhere[6] Laxatives used excessively and for prolonged periods of time are a cause of diarrhoea and surreptitious laxative use occurs in the elderly[74]. Cognitive impairment also may lead to inadvertent laxative abuse, to treat constipation which increases with age and is a problem in about one third of elderly persons[75]. Radiation enteropathy Diarrhoea is a common side-effect of radiation therapy for malignancies in the elderly such as carcinoma of the cervix, uterus, rectum and prostrate. The availability of supravoltage radiation with minimal or absent skin damage has resulted in higher doses of radiation causing an increase in gastrointestinal problems such as diarrhoea[76]. The small intestine is particularly vulnerable to ionising radiation due to the rapid turnover of epithelial cells[77]. Greater damage to the less mobile duodenum and terminal ileum results in bacterial overgrowth and diarrhoea, malabsorption and stricture formation[76] In the colon the caecum and recto sigmoid, as they are fixed in the pelvis experience more mucosal damage, bleeding and in about 50 per cent of patients diarrhoea occurs[76]. In both the small and large intestine diarrhoea may result soon after therapy, often with spontaneous recovery[78]. In about 10 per cent of patients, even after two to three decades, diarrhoea may be a problem from chronic radiation damage[77]. Surgical intervention The most common cause of diarrhoea due to surgery is from bowel resection. Chronic diarrhoea as a result of surgery for peptic ulceration is now rarely seen with the availability of effective medical therapy.
Faecal Incontinence Faecal incontinence (spurious diarrhoea, overflow diarrhoea) is common in the elderly and about 10 per cent of elderly persons in institutional care experience this problem at least once a week[79]. The prevalence is 42 per cent in geriatric wards[80]. Other causes of faecal incontinence associated with aging are impaired rectal sensation and reservoir capacity, impaired puborectalis function and cognitive impairment. Diverticular disease The risk of developing diverticula of the colon increases with age and diarrhoea is a consequence of diverticulitis when acute or chronic inflammation due to a mechanical obstruction within the diverticula occurs[81]. The clinical picture of diverticulitis is a febrile illness with bloody diarrhoea, lower abdominal pain, tenderness, and a possible mass due to an abscess. Carcinoma colon Diarrhoea or diarrhoea alternating with constipation associated with rectal blood loss, are prominent symptoms of carcinoma of the colon, which is the most common malignancy in old age after carcinoma of the prostate. The rectosigmoid is the site of tumour in two thirds of cases. Pain is a symptom of advanced disease. A malignancy should be urgently excluded when iron deficiency anaemia without an obvious cause, or in instances of subtle changes in bowel habit, the passage of frank blood, or occult bleeding, or weight loss. Ischaemic colitis Ischaemic colitis occurs more frequently in elderly patients and presents with diarrhoea, cramping lower (usually left-sided) abdominal pain and the passage of frank blood or clots. This entity is associated with illnesses of old age including polycythaemia, diabetes mellitus, arteritis and arteriosclerosis[82], and digitalis preparations[83]. The diagnosis is based on the typical barium enema findings of "thumb printing" or "saw tooth" indentations The irritable bowel syndrome Due to its strong association with psychosomatic factors the irritable bowel syndrome (IBS) is particularly relevant to the elderly. Significant life-events occur in old age such as bereavement of a spouse, ill-health, physical and mental incapacity, relocation from the family home or dependence on a carer. IBS is defined by Heaton[84] as: "chronic or recurrent symptoms attributable to the intestines and occurring in varying but characteristic combinations of abdominal pain, bloating (distension) and symptoms of disordered defecation, especially urgency, straining, feeling of incomplete evacuation and altered stool form and frequency". Therapy is directed towards pain relief (antispasmodic drugs) diarrhoea (loperamide, diphenoxylate) and constipation.
Diarrhoea is an important problem in and to the elderly associated with multiple and diverse causes. The many predisposing and risk factors related to diarrhoea reflect aspects of the aging process directly and indirectly, as with altered defence mechanisms and physiological processes, iatrogenic causes and the effects of institutionalisation. A wider appreciation of the problem of diarrhoea by both the elderly, their caregivers and health professionals would contribute to reduce the incidence of diarrhoea and complications, improve management and enhance the quality of life of the elderly.
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