Health Articles

Benign colonic tumors have a high prevalence in the USA and Western Europe. Colorectal cancer is the second most common malignancy in the USA and Western Europe.

In the USA, about 24.000 new cases and 13,000 deaths from gastric cancer occur annually, and the incidence increases with age. The mean age at the time of diagnosis is 55 yr. Gastric cancer is more common in blacks and among poor socioeconomic groups; the male;female ratio is 2:1.
Adenocarcinoma accounts for 95% of all gastric malignancies. The worldwide incidence varies dramatically with low rates in the USA and high rates in Japan. Chile, and Costa Rica. Although an unexplained worldwide reduction has occurred over the past 50 yr (except in black men), the incidence around the gastroesophageal junction has increased. The cause of this increase is not clear, but the increase may result in part from an increase in Barren’s epithelium in the esophagus.
Lymphoma accounts for about 4% of gastric malignancies. The stomach is the most common site of primary extranodal lymphoma, accounting for up to 75% of all cases of primary Gl tract lymphomas. Most are histiocytic. Gastric lymphoma occurs mainly in men in the sixth decade.
Other malignancies, including leiomyosarcoma, carcinoid tumor, and Kaposi’s sarcoma, account for < \% of all gastric malignancies.
Gastric abnormalities with malignant potential include adenoma, mucosal atrophy with intestinal metaplasia (with or without associated pernicious anemia), and hypertrophic gastropathy. Helicobacter pylori infection may also be a risk factor for gastric adenocarcinoma and lymphoma. Gastroduodenal peptic ulcer disease has no etiologic association with gastric cancer, although a gastric ulcer that appears benign on endoscopy can have a microscopic malignant focus.
Pathology
Gastric cancer is generally classified as early or advanced, according to its gross appearance. Early gastric cancer is confined to the mucosa or submucosa and is divided into three types: (1) protruded, either polypoid or fungating; (2) superficial, either elevated, flat, or depressed: and (3) excavated. Advanced gastric cancer is defined as disease penetrating the muscularis propria with lymph node involvement: the prognosis is poor. It is divided into three types: (1) a mass lesion, either polypoid or fungating; (2) diffuse or infiltrating: and (31 ulcerated. Advanced gastric cancer may have more than one of these characteristics. If the tumor infiltration is diffuse and associated with a fibrous reaction, linitis plastica (leather-bottle stomach! may occur.
Gastric cancer develops predominantly in the distal portion of the stomach and is rarely multicentric. Cancer spreads by direct extension or metastasis via the lymphatics or the bloodstream.
Symptoms and Signs
In the early stages, symptoms may be insidious and dismissed as indite most common presenting symptom is vague epigastric dis
comfort followed by anorexia, early satiety, weight loss, hematemesis, melena, and severe abdominal pain as the tumor progresses. If the car-dia is involved, dysphagia may occur. If the prepyloric antrum is involved, symptoms of partial or complete gastric outlet obstruction (eg, epigastric fullness, nausea, and vomiting) may occur.
In the early stages, there are no specific signs of gastric cancer. In the later stages, weight loss, a palpable mass, and lymphadenopathy in the left supraclavicular region (Virchow's node) may be noted. Liver metastases can present as hepatomegaly. Dermatologic signs of gastric cancer include acanthosis nigricans and dermatomyositis.
Diagnosis
An upper Gl tract barium study is usually the initial test, but lesions are frequently missed. The double-contrast technique can improve detection, so that a mass, an infiltrating ulcer, or only thickened rugae can be seen.
Upper Gl endoscopy allows visualization of most lesions, provides a means of obtaining tissue for biopsy and cytologic examination, and yields the diagnosis in > 90% of cases. Endoscopic ultrasonography may provide information regarding the depth of invasion. When older patients can tolerate only one test, endoscopy is generally preferred to x-ray studies.
Other laboratory procedures provide little help. Elevated levels of carcinoembryonic antigen (CEA) and fetal sulfoglycoprotein and decreased levels of pepsinogen have been noted in about 15% of patients with gastric cancer, but because of poor sensitivity and specificity, these measures have no clinical role. An abdominal CT scan helps evaluate the extent of disease.
The differential diagnosis includes peptic ulcer and pancreaticobili-ary tract disease. Patients who have undergone partial gastrectomy or gastroenterostomy for peptic ulcer disease more often have gastric polyps, epithelial dysplasia, and carcinoma in the remaining gastric pouch beginning 10 to 15 yr after surgery. The only real chance of curing gastric cancer is early diagnosis and surgical excision.
The patient with gastric lymphoma presents with symptoms similar to those of gastric carcinoma. The radiographic appearance may also be similar, although large gastric folds and evidence of infiltration into the duodenum are more typical of lymphoma than of carcinoma. Endoscopy may confirm the diagnosis if multiple directed biopsies combined with brush cytology yield positive results. Because the lesions are submucosal, this approach may be unsuccessful, and laparotomy may be needed.
Treatment
Surgery is widely accepted as the initial therapy for early gastric cancer. Radiation therapy alone is ineffective for adenocarcinoma. Radiation therapy after resection is commonly used with good results in patients with gastric lymphoma. Chemotherapy for metastatic adenocarcinoma has a poor response rate. Chemotherapy for gas’tumors arc symptomatic. Adenocarcinoma produces symptoms more often than other small-intestine tumors. Adenocarcinoma is generally found in ihe proximal small intestine, predominantly in the duodenum. Predisposing factors include Klulen enteropathy, Crohn’s disease, and Ihe (il polyposis syndromes. Mich as Gardner’s syndrome. Tumors arc usually annular and constricting. Lymphoma occurs predominantly in the ileum and is usually of B-celt origin; lymphoma of T-cell origin is associated with adult celiac disease. Leiomyosarcoma is as common as lymphoma.
Symptoms, Signs, and Diagnosis
Although most small-intestine malignancies are asymptomatic, 60% to 75% of symptomatic small-intestine tumors arc malignant. Patients with advanced disease present with abdominal pain resulting from intestinal obstruction, recurrent intussusception, mesenteric thrombosis, perforation. (j| hemorrhage, or a palpable abdominal mass. The carcinoid syndrome, characterized by diarrhea and flushing, occurs usually when hepatic metastases develop. Lymphoma, especially Hodgkin’s disease, may present as malabsorption syndrome wilh weight loss, diarrhea, malaise, weakness, and edema.
Preoperative diagnosis is generally made by small-intestine \ i ay and CT scan. Endoscopy may provide visualization and tissue for diagnosis, and arteriography may show vascular malignancies. With advanced carcinoid tumors, urinary 5-hydroxyindoleacetic acid (5-H1AA) levels may be elevated.
Treatment
The usual treatment is surgical reseclion. Radiation therapy and chemotherapy are potentially effective only for lymphoma. The 5-yr survival rate for patients with adenocarcinoma is 30%; (”or those with lymphoma and leiomyosarcoma, it approaches 50%. The prognosis for patients wilh carcinoid tumors can be good wilh survival commonly exceeding 10 yr. Oclrcotide is often effective in treating severe flushing and diarrhea in palients wilh the carcinoid syndrome.

In clinical medicine, attempting !o separate the effects of aging from those of disease is a recurring challenge. The elderly who have no significant disease but whose biologic age appears greater than (heir chronologic age (as determined largely by functional assessment) are described as “frail.” Understanding the role of such frailty in liver aging isjust beginning. Mos! research on changes in the aging liver has been done in rodents and may not necessarily be extrapolated to humans.
There are no peculiar or characteristic diseases of the aged liver. Kur-thermore, the liver ages gracefully, without producing changes in the results of so-called liver function tests. In this context, the effects of aging on liver appearance, histologic characteristics, physiology, drug metabolism, and response to stress require more detailed comment.
Appearance
Autopsy studies and peritoneoscopy show that the liver becomes brown and more fibrotic with age. The increased capsular and parenchymal fibrosis should not be confused with cirrhosis. With age. hepatic weight declines: autopsy studies show a decrease of about 25% between ages 20 and 70 in men and women. In vivo ultrasound studies also show that liver volume is 17% to 28%’ lower in those over age 65 than in those under age 40.
Histologic Characteristics
Studies of age-related changes in hepatic fine structure have reported disparate results. Historically, it has been believed that human hepato-cytes enlarge with age; however, some studies report no change in size. Several studies on rodents report (hal hepatocytes enlarge with age, whereas others report that they enlarge with maturation but diminish with senescence.
Some studies report polyploidy and increases in nuclear size and binuclear liver cells with aging, although other studies report no significant changes. The structural changes found in hepatocyte mitochondria have been as disparate as an increased number of swollen, vacuolated mitochondria and a decreased number of mitochondria per liver volume. Unlike other componenls of hepatocytes, lysosomes and dense bodies increase consistency with age.
The brown pigment buildup with aging represents a lifetime accumulation of unexcretable metabolic residue and generally has no physiologic significance. An increased number of lipofuscin granules in hepatocytes accounts for much of this pigment. Lipofuscin is a brown pigment resulting from the accumulation of end-stage metabolic products of lipids and proteins; thus, it is a wear and tear pigment.
Hepatic changes caused by malnutrition and those caused by aging are similar in some ways. Both are associated with a brown, atrophic-appearing liver. However, in malnutrition the number of hepalocytes is normal, but they are smaller; in aging there are fewer hepatocyles. but they are usually larger.
Physiology
Decreased hepatic weight is accompanied by diminished hepatic blood flow (resulting from decreased splanchnic blood flow). In dye elimination tests using indocyanine green, the apparent hepatic blood flow declined by 35% in persons over age 65 compared with those under age 40. The diminished liver mass and blood flow may account for some changes in drug elimination in aging patients.
Protein synthesis and degradation appear to decrease with age. Several methods have been used to study hepatic protein synthesis, including cell-free systems, in vivo studies, hepatocyte suspensions, and liver perfusion systems. Although the results of the studies do not completely agree, most evidence points to decreased protein synthesis with age. However, the degree of decrease appears to vary widely among various proteins. No scx-rclated differences are apparent in studies involving male and female rodents.
Degradation of several proteins, including some enzymes, has been studied by following radiolabeled amino acids, using several techniques. The results suggest a decreased rate of degradation with age. The accumulation of abnormal proteins with aging may reflect a decreased ability of cells to degrade these proteins. In the only study on abnormal liver proteins as a function of age, a significant increase in their half-life was observed in mice. The extent to which these abnormal proteins are functional or represent inadequately broken down, deteriorated “junk” proteins is unclear.
As the liver ages, regeneration is delayed but not greatly impaired. In older rats mitotic activity is decreased more than in younger rats after partial hepatectomy. Although mitotic activity decreases, the hepato-cytes that do divide appear to undergo more cell cycles, and thus regeneration catches up.
Aging does not alter results of the so-called liver function tests, which measure hepatic damage, eg. hepatocellular injury (aminotransferases), selected protein synthesis (alkaline phosphatase), or transport of hepatocytes (bilirubin), rather than overall function. Thus, abnormal values for these tests in the elderly reflect disease, not the effects of aging.
Drug Distribution and Metabolism
Because the elderly take more prescription medications than any other age group, they are more likely to have adverse drug reactions. Therefore, much effort has been directed toward understanding the changes in drug metabolism that occur with aging. Many factors may influence drug disposition in the elderly, including changes in body composition (decreased lean body mass and increased fat), a general decrease in serum albumin concentration, decreased renal function, and environmental influences including dietary changes (see Ch. 21).
With the age-related increase in body fat. the distribution of lipid-soluble drugs increases. If plasma clearance remains unchanged, the half-life of the drug is prolonged, and the potential for toxic concentrations increases unless the dosing interval is modified appropriately.
With drugs that have a high rate of hepatic extraction, a significant change in bioavailability can occur with aging. Such drugs usually undergo significant metabolism before reaching the systemic circulation. Although absorption across the gut does not change significantly with aging, first-pass metabolism may decrease, most likely from reduced intrinsic clearance, and lead to increased bioavailability. Oral doses of nifedipine, propranolol, morphine, and labetalol, for example, achieve significantly higher plasma concentrations in the elderly.
The two major drug-binding proteins in serum are human serum albumin and ai-acid glycoprotein. With increasing age, serum albumin tends to decrease, whereas cu-acid glycoprotein tends to remain the same. Thus, in older patients there is less albumin-bound drug and more free drug. Because therapeutic effect is usually related to the amount of free drug, decreased serum albumin can result in increased levels of active drug. The clinical significance of this depends on the size of the increased free fraction, pharmacokinetics, and the drugs therapeutic index. Although large increases in the free fraction have been reported after acute administration of a few drugs (including naproxen, salicylate, and valproic acid) in the elderly, once steady state is achieved (chronic administration), increased total body clearance minimizes the clinical impact.

Recurrent or chronic pancreatic inflammation resulting in recurrent or persistent abdominal pain secondary to anatomic damage (calcification, ductal changes, fibrosis) or functional damage (exocrine or endocrine insufficiency) to the pancreas. Pancreatic exocrine or endocrine insufficiency develops without pain in some patients, especially elderly patients, many of whom have associated pancreatic calcification.
Etiology
In the elderly, the most common forms of chronic pancreatitis with pancreatic insufficiency result from heavy alcohol intake for more than 15 yr, trauma, vascular disease, abdominal radiation therapy, and pancreatic carcinoma. Rarely, primary pancreatic atrophy and pancreatic lipomatosis cause steatorrhea and diabetes mellitus. However, a few of these patients are alcoholics without abdominal pain, thus raising the question whether this is a true entity.
Symptoms and Signs
In 90% of younger patients with chronic pancreatitis, the predominant symptom is recurrent, severe abdominal pain. In elderly patients. the pain is mild or absent—except in those with pancreatic carcinoma and secondary pancreatic insufficiency. Characteristically, the elderly have an abrupt onset of frequent bowel movements producing bulky, malodorous, greasy stools that are difficult to flush. Rectal seepage of oil and oil in the toilet bowl may be the presenting complaints. A weight loss of 6 to 20 kg occurs secondary to malabsorption and poor oral intake. Polyuria and polydipsia may precede the abnormal bowel movements. Less common clinical manifestations include arthritis, subcutaneous fat necrosis, and intramedullary fat necrosis with associated bone pain.
Diagnosis
Diffuse, stippled pancreatic calcification on a flat plate film of the abdomen is diagnostic. Ultrasonography and CT scan should be performed on patients with abdominal pain to rule out pancreatic pseudocyst and pancreatic carcinoma. Pancreatic insufficiency is documented by a bentiromide urinary excretion test in which the cumulative 6-h excretion of aminobenzoic acid (PABA)is < 50% of the ingested synthetic peptide bentiromide. The serum trypsin-like immunoreactivity test reveals a value < 20 ng/mL (normal is 20 to 80 ng/mL), which is characteristic of pancreatic insufficiency. However, this test is less sensitive than the bentiromide test.
Endoscopic retrograde cholangiopancreatography shows an irregularly stricturcd, dilated main pancreatic duct with a beaded appearance that is almost diagnostic of chronic pancreatitis. Steatorrhea can be documented by the Sudan III stain Tor qualitative fat or by a quantitative stool fat or NC-labeled triolein breath test.
Treatment
Alcohol ingestion should be eliminated. Patients with pain should be given nonaddictive analgesics—salicylates, acetaminophen, and nonsteroidal anti-inflammatory drugs. Large doses of patent pancreatic enzyme preparations high in lipase and proteolytic enzymes are required: 6 to 8 tablets (Ilozyme, Viokase), 6 to X capsules (Ku-Zyme HP, Cotazym), or 3 microencapsulated capsules (Pancrease) with each meal. Because gastric acid inactivales lipase, the non-microencapsu-laled forms of pancreatic enzymes (eg, Viokase. Colazym) may be given with H2-receptor antagonists. However, enteric-coated preparations (eg. Pancrease, Creon) are used more commonly because of fewer GI side effects, lower cost, and greater convenience. The prognosis is generally good except in patients with pancreatic carcinoma and in those incapable of discontinuing alcohol consumption.

Intraluminal small intestinal bacterial overgrowth accompanied by nutrient malabsorption secondary to carbohydrate catabolism by ^ram-negative aerobes, bile acid deconjugation by anaerobes, cobalamin binding by anaerobes, and patchy damage to small intestinal epithelial cells.
Etiology
In healthy adults, the proximal lumen of the small intestine contains 0 to 104 microorganisms per milliliter, consisting of aerobes and facultative anaerobes, which are largely oral flora. This relative sterility is maintained by normal gastric acid secretion, normal peristalsis of the proximal small intestine, and luminal immunoglobulins. In persons age 70 and older, however, hypochlorhydria or achlorhydria commonly allow bacterial overgrowth.
Several conditions can lead to stagnation of the small intestine, including a large duodenal diverticulum, multiple jejunal diverlicula, stricture, fistulas, radiation enteritis, afferent loop of Billroth II partial gastrectomy, surgical blind loop, and resection of the ileocecal valve. Motor abnormalities secondary to scleroderma, idiopathic intestinal pseudo-obstruction, and diabetic autonomic neuropathy also can lead to bacterial overgrowth in the small intestine.
About 20% of patients over age 65 who undergo an upper GI series have a duodenal diverticulum. A similar percentage is found in postmortem studies using plaster casts of the duodenum. By contrast, jejunal diverliculosis is uncommon, with an autopsy prevalence of 0.5%. Although patients with this disease are usually asymptomatic, they may have many large jejunal diverticula, leading to bacterial overgrowth and malabsorption offal and vitamin B12. Severe malabsorption has been described in patients with duodenal and jejunal diverticulosis who also have chronic pancreatic insufficiency; these patients did not respond to broad-spectrum antibiotics alone but did respond when pancreatic enzymes were added.
Symptoms and Signs
Patients may be asymptomatic or may present with watery diarrhea secondary to deconjugated bile acids, hydroxy fatty acids, and organic acids; clinically significant steatorrhea resulting in weight loss; bone pain and pathologic fractures; easy bruising from vitamin K deficiency; night blindness from vitamin A deficiency; hypocalcemic tetany; and weakness and easy fatigability from cobalamin deficiency. Some patients may present with a dimorphic anemia, both macrocytic and microcytic, the latter resulting from microulcerations of ihe stagnant loop thai produce occult blood loss and guaiac-positive stools. Patients wilh strictures and small intestinal pseudo-obstruction have symptoms of abdominal distention (nausea and crampy periumbilical pain) before the onset of diarrhea, steatorrhea, and anemia.
Diagnosis
An increase in stool weight and evidence of excessive fat (on Sudan 111 stain, 72-h stool fat. or l4C-labeled triolein breath test) should be documented. An upper GI series with small intestine follow-through identifies duodenal diverticulum, jejunal diverticula, stricture, gas-trojejunocolic fistulas, afferent loop syndrome, intestinal pseudoobstruction, scleroderma, and Crohn’s disease. A small intestine biopsy excludes celiac disease, Whipple’s disease, eosinophilic gastroenteritis, and giardiasis. Reduced excretion of labeled cobalamin that is not corrected by intrinsic factor but is corrected by broad-spectrum antibiotics confirms vitamin B12 deficiency secondary to bacterial overgrowlh.
The 1-gm l4C-labcled xylose breath test is the test of choice for detecting bacterial overgrowth; it reveals elevated I4CO2 levels within the first 60 min. Although culture of the small intestine’s contents has excellent specificity, it is cumbersome. The l4C-labeled cholylglycine breath test is easy to perform but lacks specificity.
Treatment
The recommended treatment is a 10-day course of cephalexin 250 mg qid and metronidazole 250 mg lid orally. Many patients respond to treatment in 7 to 10 days, a few require repeat therapy, and rarely a patient needs continuous therapy for months. Chloramphenicol 50 mg/kg/day orally in four divided doses for 7 to 14 days is recommended for patients who do not respond to cephalexin and metronidazole. Cobalamin deficiency in malabsorption responds to monthly IM injections of 100 μg vitamin Biz. Deficiencies of calcium, vitamin D, and vitamin K should be corrected as in celiac disease (sec above).

A genetic disease involving malabsorption of many nutrients, resulting from characteristic, if not specific, pathologic changes in the small intestinal mucosa induced by ingestion of the giiadin fraction of gluten. Giiadin is a mixture of high-molccular-weight cereal proteins found in wheat, rye, oats, and barley. In mosl patients, prompt clinical, biochemical, and histologic improvement follows the withdrawal ol’gliadin-containing cereal from the diet.
Celiac disease occurs throughout the world, but its prevalence is unknown. The incidence, which varies considerably in different parts of the world, is highest in western Ireland (1:300). Recent research indicates that the affected population is older than previously recorded; many cases are diagnosed during or after the seventh decade. This age-related skew—seen in the USA, Sweden, Scotland, and Ireland—probably reflects clinicians’ increased willingness to consider the diagnosis in the elderly.

Etiology and Pathogenesis
Celiac disease is closely associated with the human leukocyte antigens HLA-DQW2, HLA-DR3, and (to a lesser degree) HLA-B8.
Various mechanisms of etiology and palhogenesis have been proposed. One theory holds (hat the small inteslinal absorptive cell lacks one or more enzymes that normally break down giiadin peptides, and Ihe residual polypeptides injure the epithelial absorbing cells. Another theory suggests that susceptible patients absorb giiadin, which causes a humoral and a T-lymphocyle-dependent immune reaction, resulting in lysis and death of absorptive cells with a compensatory increase in crypt cell proliferation and a flat mucosal lesion. A third theory holds that glulen behaves like a lectin and binds (o pathologically altered carbohydrate structures of (he luminal small inteslinal cells.
Also, an amino acid sequence homology has been shown between a protein of the human adenovirus and a major α-gliadin component. This finding suggests that the immune response to antigenic determinants produced during a previous intestinal viral infection may be important in the pathogenesis of celiac disease. However, studies in animals and humans have failed 10 support this hypothesis and suggest that persistence of the adenovirus is not a major element in the pathogenesis of celiac disease. Thus, this disease probably has many causes, with genetic, immunologic, biochemical, and perhaps environmental factors all playing a role.
Symptoms and Signs
The clinical manifestations of celiac disease in the elderly arc subtle and variable. Most patients have steatorrhea, diarrhea, weight loss, and malnutrition, which may be mild. Certain nutritional deficiencies such as iron deficiency, osteomalacia with bone pain, or hypoprothrombin-emia; or fatigue with mild hematologic abnormalities such as unexplained macrocytosis, low folate reserve, a peripheral smear showing Howell-Jolly bodies (splenic atrophy), target cells, or thrombocytopenia may obscure the underlying disorder and prevent early diagnosis.
Physical findings vary among patients. Some appear chronically emaciated with pale mucous membranes and dry. scaly skin; in a small number, the dry, scaly skin is hyperpigmentcd. Blood pressure is normal or low. and peripheral edema often occurs. The hair may be thin, and the fingers may be clubbed. Usually, glossitis and cheilosis are present. The striking finding is abdominal distention wilh hyperactive bowel sounds. Other findings include positive Trousseau’s and Chvos-lek’s signs (associated wilh hypocalcemia), ecehymoses and hematomas resulting from decreased vitamin K absorption, skeletal deformities secondary to osteoporosis and osteomalacia, loss of height, evidence of peripheral neuropathy, and subacute combined degeneration.
Laboratory Findings
With fat malabsorption, microscopic examination of a stool specimen stained with Sudan III reveals increased tat droplets. A 24-h stool specimen usually weighs more than the normal 200 gm. Chemical fat determination of a 3- to 6-day stool specimen obtained while the patient ingests a 100-gtn fat diet shows fat excretion of IOlo40gm/24 h (normal is < 6 gm/24 h). A l4C-labclcd triolein breath test showing an increase in labeled breath carbon dioxide suggests fat malabsorption.
A 5-h urinary xylose excretion after ingesting 25 gm D-xylosc is 0.5 to 2.5 gm (normal is > 4.5 gm), and the blood level of xylose at 1 his < 30 mg/tlL (normal is > 30 mg/dL). Because of decreasei! renal function in the elderly, both urinary excretion and blood levels of xylose should be obtained. Hematologic findings include iron deficiency anemia with hy-pochromia and microcytosis on blood smear. Some patients have a megaloblastic anemia secondary to folic acid or vitamin Bi; deficiency or both. Serum folate levels range from 0.7 to 3.5 ng/mL (normal is > 3.5 ng/mL).
In patients with severe ileal damage. Ihe Schilling test reveals an excretion of < 8% of "Co-cyanocobalamin. This finding cannot be corrected by administering intrinsic factor or broad-spectrum antibiotics, thus differentiating celiac disease from pernicious anemia and blind-loop variants, respectively.
A useful screening test, serum carotene measurement invariably reveals levels < 50 μg/dL. Low levels of serum albumin, cholesterol. and vitamin A and a low prothrombin time (which can be corrected with IV vitamin K) may be found. In patients with osteomalacia, serum calcium is low, serum phosphorus is normal or low, and bone alkaline phosphatase is elevated. A bone biopsy revealing increased osteoid foci and widened osteoid seams confirms the diagnosis of osteomalacia. A generalized deficiency of intestinal disaccharidasc activity occurs secondary to brush border damage. Lactase is most affected. A lactose-hydrogen breath lest after lactose ingestion shows an increase in breath hydrogen > 20 ppm within 3 h.
Diagnosis
Diagnosis is based on characteristic histologic changes in a blind or endoscopic peroral jejunal mucosal biopsy. Those changes include a loss of villus architecture, markedly elongated intestinal crypts, cuboi-dal luminal epithelial cells with a loss of nuclear polarity, cytoplasmic basophilia, and vacuolization. The brush border is markedly attenuated. There is an apparent increase in intraepithelial cells. In the lamina propria, increased cellularity consists of immunoglobulin-producing plasma cells (IgM). lymphocytes, and some eosinophils and polymorphonuclear leukocytes.
Characteristically, the abnormal mucosa is confined to the proximal small intestine, but in severe cases, it extends to the entire small intestine. The lesions are not specific for celiac disease, but most patients who have them and who live in Ihe temperate zone have this disease and respond clinically, biochemically, and histologically to a gluten-free diet. Clinical or biochemical relapse or worsening of jejunal biopsy findings with a gluten or gliadin challenge confirms the diagnosis.
Measurement of circulating endomysial. reticulin, and gliadin antibodies is an important advance in Ihe serologic diagnosis of celiac disease. The IgA-class endomysial and reticulin antibodies are both sensitive and specific markers: the IgA-class gliadin antibodies are specific but less sensitive markers. All lliese markers may help in monitoring patient compliance with a gluten-free diet.
Treatment
The treatment of choice is a well-balanced diet containing normal amounts of fat, protein, and carbohydrate but no foods containing wheat, rye, barley, or oats. Lactose-free milk is recommended for patients with lactase deficiency. Symptoms and signs usually show improvement within days or weeks but may lake months.
Most patients who do not respond either are not adhering to the diet or have another disease such as giardiasis, lymphoma, Whipple’s disease, or collagenous sprue. (A rare disease, collagenous sprue is characterized by a severe lesion similar to the celiac disease lesion hut with broad bands of fibrosis and collagen beneath the basement membrane. The prognosis is generally poor.)
A few patients respond initially to gluten withdrawal but then relapse despite strict adherence lo the diet. Some of these refractory or unclassified celiac disease patients may respond lo treatment with high doses of corticosteroids (such as prednisone 60 mg/day for about I mo) or other immunosuppressive drugs, such as az.athioprine or cyclophosphamide. Others, despite such therapy, have a relentless course usually culminating in death.
Supplemental therapy: Patients with iron deficiency anemia should receive supplemental ferrous sulfate 325 mg tid, while those with folic acid deficiency should receive folic acid 5 mg/day for I mo, followed by a maintenance dosage of 1 mg/day. Patients with vitamin B12 deficiency should receive 100 μg vitamin B12 IM daily for 2 wk, then 100 μ-g monthly. About 1200 mg/day of elemental calcium corrects calcium deficiency (see TABLE 58-1); I to 4 gm/day of magnesium gluconate corrects magnesium deficiency.
Patients with radiologic evidence of osteopenic bone disease require I to 3 gm/day of elemental calcium plus 50,000 u./day of vitamin D. Vitamin K 10 mg IV should be given slowly (ie, 1 mg/min) to correct prolonged prothrombin time. Severe reactions, including fatalities, have occurred during or immediately after IV injection. Thus, IV vitamin K should be given only to quickly correct prothrombin time; then oral vitamin K (phytonadione 10 mg once a day) should be given. Therapeutic formula multivitamin preparations containing vilamin A, thiamine, riboflavin, niacin, pyridoxine, vitamin C, and vitamin E should be administered to patients with prolonged, severe malabsorption.

A spectrum of symptoms and signs usually resulting from excessive fat excretion {steatorrhea); varying degrees of panmalabsorption of fat-soluble vitamins, water-soluble vitamins, electrolytes, and water; and maldigestion of carbohydrates and proteins.
The nutritional status of elderly persons is influenced by (he effects of age on nutrient digestion and absorption. Aging does not significantly affect the structure and function of the exocrine pancreas, nor does it impair digestive capacity. Maldigestion and malabsorption occur only when more than 90% of pancreatic function is lost. Similarly, the small intestine has a large reserve capacity, and aging has only subtle influences on the digestive and absorptive processes.
The well-nourished elderly person has a reduced mucosal surface area wilh a slight reduction in villus height but normal enterocyte height, inlraepilhelial lymphocyte counts, and lamina propria cellular-ity. Jejunal brush border lactase and alkaline phosphatase levels decrease with age; other disaccharidase values are relatively stable, until after the sevenlh decade, when they decline. Fal absorption is normal, but absorption offal-soluble vitamins A and K increases, while absorption of vitamin D decreases.
Measurement of breath hydrogen to determine carbohydrate absorption shows excess hydrogen excretion in one third of those over age 65. This abnormality may have several causes and is due in part to achlor-hydria, abnormal bacterial flora, delayed gastric emptying, and slow intestinal transit; the key element is bacterial overgrowth. Vitamin B12 and folate absorption remain normal, while nonheme iron absorption decreases. Thus, absorption and digestion disorders in the elderly are not related to physiologic processes but to disease states.
Malabsorption falls into three pathophysiologic categories: intraluminal maldigestion secondary to pancreatic insufficiency, intraluminal bacterial overgrowth, and biliary tract disease; mucosal lesions resulting from celiac disease, Crohn’s disease, and ileal resection > 100 cm; and lymphatic dysfunction such as retroperitoneal fibrosis, intestinal lymphangiectasia, and retroperitoneal malignancy. In the elderly, malabsorption has three main causes: celiac disease, bacterial overgrowth syndrome, and pancreatic insufficiency.

Salmoncllae are gram-negative, non-spore-form ing bacilli that belong lo the family of Knterobacleriaceae. Three species exist: Salmonella typhi, Salmonella choleraesuis, and Salmonella enteritidis. S. enteritidis typhimttrium is Ihe serotype most commonly causing inl’eclion in humans. It invades mucosal cells and multiplies within them, elicil-ing a polymorphonuclear leukocyle response. Fluid accumulation within the intestinal lumen is related lo the elaboration of heat-labile and heat-stable enterotoxins.
Gastroenteritis caused by Salmonella is found more frequently in patients > 60 yr. partially because of reduced gastric acidity. Salmonella bacteremia also occurs more often in the elderly lhan in young adults wilh Salmonella gastroenteritis and is potentially more harmful because it tends to colonize the endothelial surfaces of atherosclerotic aortic aneurysms. An outbreak in a long-term care facility may cause a local epidemic.
Symptoms and Signs
The initial clinical manifestations of S. enteritidis typhimurium in the elderly include nausea, vomiting, and a chill followed by colicky abdominal pain, diarrhea, and vomiting. The diarrhea ranges from a few loose stools lo as many as 30 bowel movements daily. Characteristically, the stools are walery. green, and malodorous, wilh varying amounts of mucus. Some patients present with high fever and bloody, mucoid diarrhea, suggesting significant colonic involvement. The illness may last only a week or as long as 3 mo. The average course is 3 wk. The main complications are bleeding, toxic megacolon, and overwhelming sepsis.
Diagnosis and Treatment
Microscopic examination of methylene bine-stained specimens reveals moderate numbers of polymorphonuclear leukocytes. Stool should be cultured on selective or differential media.
Usually, antimicrobial therapy is nol used for Salmonella gastroenteritis. However, elderly patients—especially Ihose with underlying malignancies, lymphoproliferative disorders, cardiovascular diseases, aneurysms, and vascular grafts—should he given ampicitlin 50 to 100 mg/kg/day in divided doses orally or parenterals for 10 to 14 days. Based on the incidence of relapse, such therapy may be continued for up to 21 days. Alternatively, TMP-SMX is given at a dosage of 10 mg/kg/day TMPand 50 mg/kg/day SMX to a maximum of 4 tablets/day (320 mg and 1600mg)for 2 wk. Other alternatives include ciprofloxacin and several other third-generation cephalosporins.

Shigellae are a group of gram-negalive enteric organisms. Four major subgroups exist: group A-serotypcs of Shigella dysenteriae, group B-serotypes of Shigella flexneri, group C-serotypes of Shigella boydii, and group D-serotypes of Shigella sonnet- The most common serotype is S. sonnet, which is responsible for 60% to 80% of Shigella dysentery in the USA.
Symptoms and Signs
The illness is characterized by lower abdominal pain, rectal burning, tenesmus, and diarrhea. In about 33% of patienls. dysentery stool contains blood and mucus; in about 40%, fever occurs. Severe disease causes toxicity, and patients are highly febrile. The duration of symptoms is variable, bul in the elderly, the average is 7 days.
Diagnosis and Treatment
Microscopic examination of fecal samples reveals multiple polymorphonuclear leukocytes and RBCs. Stool should be cultured, and antibi olic sensitivily testing should be performed. Sigmoidoscopy and biopsy are generally not performed.
Therapy consisls of rehydration with oral and IV fluids for high-volume diarrhea and excessive vomiting. Opiate and atropine derivatives should be avoided because an inhibition of peristalsis prevents the removal of the pathogen and can exacerbate the gastroenteritis. Moderate lo severe cases require ampicillin 500 mg orally qid or I gm IVq6h. In communities where isolates are known to be resistant lo ampicillin. TMP-SMX at a dosage of 10 mg/kg/day TM P and 50 mg/kg/day SMX for 5 days should be prescribed. Alternatively, TMP-SMX 960 mg (TMP 160 mg, SMX 800 mg) orally or IV q 12 h for 5 days may be given.

The principal pathogens include Shigella, Salmonella, Campylobacter, and Yersinia. The latter two are seen predominantly in children and young adults. These four invasive pathogens involve the distal ileum and colon, producing mucosal ulceration.