gastroenterology current hot topics aging and gi disorders presented by monica j. cox, arnp-bc, gnp,...
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GASTROENTEROLOGYGASTROENTEROLOGYCURRENT HOT TOPICSCURRENT HOT TOPICS
Aging and GI Disorders
Presented by Monica J. Cox, ARNP-BC,Presented by Monica J. Cox, ARNP-BC,
GNP, MSN, MPH, DNP(C)GNP, MSN, MPH, DNP(C)
CURRENT HOT TOPICSCURRENT HOT TOPICS
ObjectivesObjectives
• Define age-related changes in the gastrointestinal tract• Discuss common G.I. problems associated with aging• Describe the risk factors for gastro-esophageal reflux
disease• Describe the risk factors for peptic ulcer development• List the causes of diarrhea and fecal incontinence in
the elderly
• Define age-related changes in the gastrointestinal tract• Discuss common G.I. problems associated with aging• Describe the risk factors for gastro-esophageal reflux
disease• Describe the risk factors for peptic ulcer development• List the causes of diarrhea and fecal incontinence in
the elderly
CURRENT HOT TOPICSCURRENT HOT TOPICS
EpidemiologyEpidemiology
• Over 35 million people aged > 65 years in the United States– 12% of the 2003 US population were older than 65
• 18.3 million aged 65-74• 12.9 million aged 75-84• 4.7 million aged ≥ 85
• 35% to 40% of geriatric patients will have at least 1 GI symptom in any year– Common problems in this age group include constipation, fecal
incontinence, diarrhea, irritable bowel syndrome (IBS), reflux disease, and swallowing disorders
• Over 35 million people aged > 65 years in the United States– 12% of the 2003 US population were older than 65
• 18.3 million aged 65-74• 12.9 million aged 75-84• 4.7 million aged ≥ 85
• 35% to 40% of geriatric patients will have at least 1 GI symptom in any year– Common problems in this age group include constipation, fecal
incontinence, diarrhea, irritable bowel syndrome (IBS), reflux disease, and swallowing disorders
Hall KE, et al. Gastroenterology. 2005;129:1305-1338. He W, et al. 65+ in the US: 2005. US Census Bureau Web site. Available at:
http://www.census.gov/prod/2006pubs/p23-209.pdf. Accessed 11/30/06.
Hall KE, et al. Gastroenterology. 2005;129:1305-1338. He W, et al. 65+ in the US: 2005. US Census Bureau Web site. Available at:
http://www.census.gov/prod/2006pubs/p23-209.pdf. Accessed 11/30/06.
CURRENT HOT TOPICSCURRENT HOT TOPICS
The “Age Wave” The “Age Wave”
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1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010 2020 20300
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YearYear
Po
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Increase in the Number of Persons Aged 65+ Years in the United StatesIncrease in the Number of Persons Aged 65+ Years in the United States
Number (millions)
Percent of population
Number (millions)
Percent of population
3 (4%)
5 (5%)
9 (7%)
17(9%)
26(11%)
31(13%)
35(12%)
40(13%)
55(16%)
72(20%)
4 (4%)
7 (5%)
12(8%)
20 (10%)
He W, et al. 65+ in the US: 2005. US Census Bureau Web site. Available at: http://www.census.gov/prod/2006pubs/p23-209.pdf. Accessed 11/30/06.
He W, et al. 65+ in the US: 2005. US Census Bureau Web site. Available at: http://www.census.gov/prod/2006pubs/p23-209.pdf. Accessed 11/30/06.
CURRENT HOT TOPICSCURRENT HOT TOPICS
CostsCosts
• $300 million to treat GI disease in older patients in 2005
• Individuals aged ≥ 65 years accounted for 60% of all medical expenditures in 2005
• $300 million to treat GI disease in older patients in 2005
• Individuals aged ≥ 65 years accounted for 60% of all medical expenditures in 2005
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
CURRENT HOT TOPICSCURRENT HOT TOPICS
Age-Related Changes in the Gastrointestinal TractAge-Related Changes in the Gastrointestinal Tract
MotilityMotility
ImmunityImmunity
Drug metabolism
Drug metabolism
VisceralsensitivityVisceral
sensitivity
• Areas identified as important to aging are:
– Pathophysiology of swallowing disorders
– Esophageal reflux
– Dysmotility symptoms
– GI immunobiology
– Cellular mechanisms of neoplasia in the GI tract
– Decreased visceral sensitivity
• Areas identified as important to aging are:
– Pathophysiology of swallowing disorders
– Esophageal reflux
– Dysmotility symptoms
– GI immunobiology
– Cellular mechanisms of neoplasia in the GI tract
– Decreased visceral sensitivity
Hormoneresponsiveness
Hormoneresponsiveness
Lithogenicbile
Lithogenicbile
Pancreas:Structure
and function
Pancreas:Structure
and function
Liver sensitivityto stress
Liver sensitivityto stress
ColonicfunctionColonicfunction
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
CURRENT HOT TOPICSCURRENT HOT TOPICS
Esophageal AgingEsophageal Aging
• Dysphagia, regurgitation, chest pain, heartburn- associated nausea are common in the elderly• “Presbyesophagus”: (age-related changes in
esophageal function)– Decreased contractile amplitude– Polyphasic waves– Incomplete relaxation of the lower esophageal sphincter (LES)– Esophageal dilation
• GERD – Common in the elderly– Impaired clearance of acid– Longer duration of reflux episodes– Atypical symptom presentation
• Dysphagia, regurgitation, chest pain, heartburn- associated nausea are common in the elderly• “Presbyesophagus”: (age-related changes in
esophageal function)– Decreased contractile amplitude– Polyphasic waves– Incomplete relaxation of the lower esophageal sphincter (LES)– Esophageal dilation
• GERD – Common in the elderly– Impaired clearance of acid– Longer duration of reflux episodes– Atypical symptom presentation
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
CURRENT HOT TOPICSCURRENT HOT TOPICS
Aging and the StomachAging and the Stomach
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Cullen DJE, et al. Gut. 1997;41:459-462.
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Cullen DJE, et al. Gut. 1997;41:459-462.
DecreasedDecreased IncreasedIncreased• Clearance of liquids from
stomach
• Perception of gastric distention
• Cytoprotective factors
•Mucosal blood flow and impaired sensory neuron function in animal models
• Contact time with NSAIDs or other noxious agents in delayed emptying
• Tendency for gastric mucosal injury in delayed emptying
• Prevalence of H. pylori associated with increased risk of bleeding peptic ulcer, pernicious anemia, and lymphoma
CURRENT HOT TOPICSCURRENT HOT TOPICS
Nutrition Nutrition
• Geriatric patients, especially aged > 85 years, are at risk for decreased food intake due to several factors: – Mobility impairment
– Ability to obtain food
– Loss of taste, may be due to decreased olfaction
– Poor dentition
– Decreased appetite
– “Anorexia of Aging,” may be related to neuroendocrine changes
– Depression
• Geriatric patients, especially aged > 85 years, are at risk for decreased food intake due to several factors: – Mobility impairment
– Ability to obtain food
– Loss of taste, may be due to decreased olfaction
– Poor dentition
– Decreased appetite
– “Anorexia of Aging,” may be related to neuroendocrine changes
– Depression
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
GASTROENTEROLOGYGASTROENTEROLOGYCURRENT HOT TOPICSCURRENT HOT TOPICS
GI Disorders Related to Aging
CURRENT HOT TOPICSCURRENT HOT TOPICS
Gastrointestinal Bleeding Is Common in the ElderlyGastrointestinal Bleeding Is Common in the Elderly
• 20%-25% GI bleeding in the lower tract– Terminal ileum– Colon– Rectum
• 75% GI bleeding in the upper tract– Esophagus– Stomach– Small bowel
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
CURRENT HOT TOPICSCURRENT HOT TOPICS
Gastrointestinal Bleeding in the ElderlyGastrointestinal Bleeding in the Elderly
• Of the 75% bleeding in the upper tract– 50% bleeding is due to NSAID use– 50% bleeding is due to ulceration or
erosions (peptic or esophageal)
• Females are at higher risk than males• Continued bleeding and rebleeding
are the highest predictors of mortality and morbidity in older patients
• Of the 75% bleeding in the upper tract– 50% bleeding is due to NSAID use– 50% bleeding is due to ulceration or
erosions (peptic or esophageal)
• Females are at higher risk than males• Continued bleeding and rebleeding
are the highest predictors of mortality and morbidity in older patients
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Image courtesy of David C. Metz, MD.
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Image courtesy of David C. Metz, MD.
CURRENT HOT TOPICSCURRENT HOT TOPICS
Colorectal Cancer in the ElderlyColorectal Cancer in the Elderly
• An estimated 106,680 cases of colon and 41,930 cases of rectal cancer were expected to occur in 2006
• 90% of all cases occur in individuals aged > 50 years
• An estimated 106,680 cases of colon and 41,930 cases of rectal cancer were expected to occur in 2006
• 90% of all cases occur in individuals aged > 50 years
American Cancer Society. Cancer Facts and Figures 2006. Atlanta: American Cancer Society; 2006.Burt RW. Gastroenterology. 2000;119:837-853.
Image courtesy of Subhas Banerjee, MD.
American Cancer Society. Cancer Facts and Figures 2006. Atlanta: American Cancer Society; 2006.Burt RW. Gastroenterology. 2000;119:837-853.
Image courtesy of Subhas Banerjee, MD.
CURRENT HOT TOPICSCURRENT HOT TOPICS
Colorectal Cancer in the ElderlyColorectal Cancer in the Elderly
• In a study of 1244 participants divided into 3 age groups who underwent screening colonoscopy, increasing age may be associated with an increased prevalence of neoplasia
• In a study of 1244 participants divided into 3 age groups who underwent screening colonoscopy, increasing age may be associated with an increased prevalence of neoplasia
13.8
26.528.6
0
5
10
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50-54 75-79 80 or older
13.8
26.528.6
0
5
10
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50-54 75-79 80 or older
Pre
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nce
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(%)
Pre
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of
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pla
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(%)
Age group (years)Age group (years)Lin OS, et al. JAMA. 2006;295:2357-2365.Lin OS, et al. JAMA. 2006;295:2357-2365.
n = 1034 n = 147 n = 63
CURRENT HOT TOPICSCURRENT HOT TOPICS
Aging-Associated Changes in Colonic MotilityAging-Associated Changes in Colonic Motility
• Common disorders observed in the elderly that are correlated with colonic motility are: – Constipation – Diverticular disease – Diarrhea– Fecal incontinence
• There are age-associated reductions in myenteric neurons, calcium influx, and tensile strength of the collagen and muscle fibers• No clear effect of age on colonic transit, as many
constipated older patients appear to have normal transit times
• Common disorders observed in the elderly that are correlated with colonic motility are: – Constipation – Diverticular disease – Diarrhea– Fecal incontinence
• There are age-associated reductions in myenteric neurons, calcium influx, and tensile strength of the collagen and muscle fibers• No clear effect of age on colonic transit, as many
constipated older patients appear to have normal transit times
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Petruzziello L, et al. Aliment Pharmacol Ther. 2006;23:1379-1391.
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Petruzziello L, et al. Aliment Pharmacol Ther. 2006;23:1379-1391.
CURRENT HOT TOPICSCURRENT HOT TOPICS
Coronary heart diseaseCoronary heart disease
Asthma Asthma
DiabetesDiabetes
MigrainesMigraines
HypertensionHypertension
ConstipationConstipation
Prevalence in millionsPrevalence in millions00 2020 4040 6060 8080
Prevalence of Selected Diseases in US AdultsPrevalence of Selected Diseases in US Adults
*Prevalence in North Americans*Prevalence in North Americans
Pleis JR and Lethbridge-Cejku M. Summary health statistics for U.S. adults: National health interview survey, 2005. National Center for Health Statistics.
Vital Health Stat 10(232). 2006. Available at: http://www.cdc.gov/nchs/data/series/sr_10/sr10_232.pdf. Accessed 3.5.07.
Higgins PDR, et al. Am J Gastroenterol. 2004;99:750-759.
1414
1616
1616
3333
4949
63*63*
Prevalence of Constipation Compared to Other Common DiseasesPrevalence of Constipation Compared to Other Common Diseases
CURRENT HOT TOPICSCURRENT HOT TOPICS
Diverticular DiseaseDiverticular Disease
• An abnormality in the aging colon involving decreased tensile strength of the muscle wall
• By age 50 years, one third of Americans will have diverticulosis coli; by age 80 years, two thirds will be affected– Incidence less than 5% among those aged
< 40 years– Incidence greater than 60% by age 85 years– Mean age at presentation is 60 years
• The majority of those affected are asymptomatic
• An abnormality in the aging colon involving decreased tensile strength of the muscle wall
• By age 50 years, one third of Americans will have diverticulosis coli; by age 80 years, two thirds will be affected– Incidence less than 5% among those aged
< 40 years– Incidence greater than 60% by age 85 years– Mean age at presentation is 60 years
• The majority of those affected are asymptomatic
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Cooperman A, et al. Diverticulitis. eMedicine Web Site. Available at:
www.emedicine.com/MED/topic578.htm. Accessed 11/3/06.Image courtesy of Jennifer Christie, MD.
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Cooperman A, et al. Diverticulitis. eMedicine Web Site. Available at:
www.emedicine.com/MED/topic578.htm. Accessed 11/3/06.Image courtesy of Jennifer Christie, MD.
CURRENT HOT TOPICSCURRENT HOT TOPICS
Diverticular Disease (Cont.)Diverticular Disease (Cont.)
• Other factors in diverticular disease:– Slow colonic transit– Increased frequency of segmenting contractions resulting in
increased water reabsorption and hard feces
• According to data from the National Demographic and Health Survey (NDHS) between 1997 and 2002– Hospital admissions increased by 14% to 261,180– Office visits increased by 14% to 1,493,865– Emergency department visits increased by 84% to 161,364
• Other factors in diverticular disease:– Slow colonic transit– Increased frequency of segmenting contractions resulting in
increased water reabsorption and hard feces
• According to data from the National Demographic and Health Survey (NDHS) between 1997 and 2002– Hospital admissions increased by 14% to 261,180– Office visits increased by 14% to 1,493,865– Emergency department visits increased by 84% to 161,364
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
CURRENT HOT TOPICSCURRENT HOT TOPICS
Diarrhea Diarrhea
• Definition: – Loose stools of more than 200 grams per day in at least
3 bowel movements per day
• Approximately 85% of all mortality associated with diarrhea involves the elderly– 73 million consultations for acute diarrhea in the United States
each year
• Between 1997 and 2002– Office visits for chronic diarrhea increased by 115% from
991,886 to 2,132,272
• Definition: – Loose stools of more than 200 grams per day in at least
3 bowel movements per day
• Approximately 85% of all mortality associated with diarrhea involves the elderly– 73 million consultations for acute diarrhea in the United States
each year
• Between 1997 and 2002– Office visits for chronic diarrhea increased by 115% from
991,886 to 2,132,272
Hoffmann JC, et al. Best Pract Res Clin Gastroenterol. 2002;16:17-36.Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
Hoffmann JC, et al. Best Pract Res Clin Gastroenterol. 2002;16:17-36.Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
CURRENT HOT TOPICSCURRENT HOT TOPICS
Causes of Diarrhea in the ElderlyCauses of Diarrhea in the Elderly
Common CausesCommon Causes
Infections
Drug-induced diarrhea
Malabsorption
Fecal impaction
Colonic carcinoma
Small bowel bacterial overgrowth
Diabetic diarrhea
Hoffmann JC, et al. Best Pract Res Clin Gastroenterol. 2002;16:17-36.Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
Hoffmann JC, et al. Best Pract Res Clin Gastroenterol. 2002;16:17-36.Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
Less Common CausesLess Common CausesCeliac disease
Inflammatory bowel disease
Thyrotoxicosis
Scleroderma with systemic manifestations
Whipple’s disease
Amyloidosis with small bowel involvement
Pancreatic insufficiency
Small bowel tumors
CURRENT HOT TOPICSCURRENT HOT TOPICS
Fecal IncontinenceFecal Incontinence
• Fecal incontinence is uncommon in the general population (2.2%) but has a significantly higher prevalence (10%) in the older population
• Fecal incontinence is uncommon in the general population (2.2%) but has a significantly higher prevalence (10%) in the older population
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
Fecal incontinence can result from:
Fecal impaction and subsequent
overflow
Internal anal sphincter
incompetence
Decreased rectal or anal
sensation
Decreased rectal or anal
sensation
Structural impairments in the pelvic floor
Anorectal damage from surgery or
irradiation
Anorectal damage from surgery or
irradiation
CURRENT HOT TOPICSCURRENT HOT TOPICS
Fecal IncontinenceFecal Incontinence
• Risk factors identified are: – Advancing age– Diabetes mellitus– Urinary incontinence– Stroke– Physical limitations– Female gender– Gynecological surgery– Perianal injury or surgery– Hypertension– Poor general health– Bowel-related factors (incomplete defecation, constipation,
straining, fecal urgency)
• Risk factors identified are: – Advancing age– Diabetes mellitus– Urinary incontinence– Stroke– Physical limitations– Female gender– Gynecological surgery– Perianal injury or surgery– Hypertension– Poor general health– Bowel-related factors (incomplete defecation, constipation,
straining, fecal urgency)
Goode PS, et al. J Am Geriatr Soc. 2005;53:629-635.Goode PS, et al. J Am Geriatr Soc. 2005;53:629-635.
CURRENT HOT TOPICSCURRENT HOT TOPICS
Implications for Elderly Suffering from Diarrhea and/or Fecal IncontinenceImplications for Elderly Suffering from Diarrhea and/or Fecal Incontinence
• Both can become a chronic problem resulting in social isolation and decreased activity out of the home
• It is important to obtain a good history to determine if fecal incontinence is due to diarrhea, urgency, obstruction, or rectal dysfunction
• Both can become a chronic problem resulting in social isolation and decreased activity out of the home
• It is important to obtain a good history to determine if fecal incontinence is due to diarrhea, urgency, obstruction, or rectal dysfunction
Hall KE, et al. Gastroenterology. 2005;129:1305-1338. Akhtar AJ, et al. J Amer Med Dir Assoc. 2005;6:54-60.Hall KE, et al. Gastroenterology. 2005;129:1305-1338. Akhtar AJ, et al. J Amer Med Dir Assoc. 2005;6:54-60.
CURRENT HOT TOPICSCURRENT HOT TOPICS
Hepatobiliary Function With AgingHepatobiliary Function With Aging
• Dynamic assessments of liver function decrease with aging
• Compared to younger adults, in healthy subjects there is a decrease of 30% - 40%* in:– Liver size– Blood flow– Perfusion
• Nonalcoholic steatohepatitis (NASH) is a common complication of obesity and diabetes mellitus– Diabetes affects 12% of the US population; > 70% of affected
individuals are in the geriatric age range– NASH may progress to cirrhosis in up to ~25% of patients– NASH increases the risk of hepatic side effects of certain drugs
• Dynamic assessments of liver function decrease with aging
• Compared to younger adults, in healthy subjects there is a decrease of 30% - 40%* in:– Liver size– Blood flow– Perfusion
• Nonalcoholic steatohepatitis (NASH) is a common complication of obesity and diabetes mellitus– Diabetes affects 12% of the US population; > 70% of affected
individuals are in the geriatric age range– NASH may progress to cirrhosis in up to ~25% of patients– NASH increases the risk of hepatic side effects of certain drugs
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Reynaert H, et al. Aliment Pharmacol Ther. 2005;22:897-905.
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Reynaert H, et al. Aliment Pharmacol Ther. 2005;22:897-905.
*Decreases occur between the 3rd and 10th decade of life*Decreases occur between the 3rd and 10th decade of life
CURRENT HOT TOPICSCURRENT HOT TOPICS
Gallbladder Function with AgingGallbladder Function with Aging
• Bile becomes increasingly lithogenic with aging– Precipitation of supersaturated bile and concomitant
crystallization of cholesterol or calcium bilirubinate
• In subjects aged > 35 years, fasting and postprandial gallbladder volumes increased– In older individuals, there was less complete gallbladder
emptying following a meal
• Aging women may be more susceptible to impaired gallbladder contractility
• Compared to young patients, cholecystitis and cholangitis in older patients have increased morbidity and mortality
• Bile becomes increasingly lithogenic with aging– Precipitation of supersaturated bile and concomitant
crystallization of cholesterol or calcium bilirubinate
• In subjects aged > 35 years, fasting and postprandial gallbladder volumes increased– In older individuals, there was less complete gallbladder
emptying following a meal
• Aging women may be more susceptible to impaired gallbladder contractility
• Compared to young patients, cholecystitis and cholangitis in older patients have increased morbidity and mortality
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
CURRENT HOT TOPICSCURRENT HOT TOPICS
Pancreatic Function With AgingPancreatic Function With Aging
• Exocrine and endocrine pancreatic function in nondiabetic patients is preserved with aging
• Incidence of pancreatic cancer is increasing in patients aged > 65 years– Significantly worse surgical outcomes in patients > 74 years– Median survival is 11 months vs. 25 months in patients aged
64 to 74 years
• Approximately half of acute pancreatitis cases are patients aged > 60 years– Gallstones are most common etiology (60%)– 40%: surgery, drugs, trauma, infection, alcohol– Mortality in elderly is 20%; twice that of general population
• Exocrine and endocrine pancreatic function in nondiabetic patients is preserved with aging
• Incidence of pancreatic cancer is increasing in patients aged > 65 years– Significantly worse surgical outcomes in patients > 74 years– Median survival is 11 months vs. 25 months in patients aged
64 to 74 years
• Approximately half of acute pancreatitis cases are patients aged > 60 years– Gallstones are most common etiology (60%)– 40%: surgery, drugs, trauma, infection, alcohol– Mortality in elderly is 20%; twice that of general population
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Hall KE, et al. Gastroenterology. 2005;129:1305-1338.
CURRENT HOT TOPICSCURRENT HOT TOPICS
SummarySummary
• The age wave will continue to increase in the next 20 years resulting in a substantial boom of the 65+ geriatric population
• Many physiological and psychological changes occur with age
• There are significant changes in gastrointestinal function that occur in geriatric patients
• Aging increases the risk of several disorders: – GI bleeding, colorectal cancer, constipation, diverticular disease,
diarrhea, fecal incontinence, hepatobiliary disorders, and pancreatic cancer
• The age wave will continue to increase in the next 20 years resulting in a substantial boom of the 65+ geriatric population
• Many physiological and psychological changes occur with age
• There are significant changes in gastrointestinal function that occur in geriatric patients
• Aging increases the risk of several disorders: – GI bleeding, colorectal cancer, constipation, diverticular disease,
diarrhea, fecal incontinence, hepatobiliary disorders, and pancreatic cancer
Hall KE, et al. Gastroenterology. 2005;129:1305-1338.Hall KE, et al. Gastroenterology. 2005;129:1305-1338.