Hypochlorhydria Abstracts 13


Measurement of gastric pH in ambulatory esophageal pH monitoring.
            (Ayazi et al., 2009) Download
BACKGROUND:  Ambulatory esophageal pH monitoring is the method used most widely to quantify gastroesophageal reflux. The degree of gastroesophageal reflux may potentially be underestimated if the resting gastric pH is high. Normal subjects and symptomatic patients undergoing 24-h pH monitoring were studied to determine whether a relationship exists between resting gastric pH and the degree of esophageal acid exposure. METHODS:  Normal volunteers (n = 54) and symptomatic patients without prior gastric surgery and off medication (n = 1,582) were studied. Gastric pH was measured by advancing the pH catheter into the stomach before positioning the electrode in the esophagus. The normal range of gastric pH was defined from the normal subjects, and the patients then were classified as having either normal gastric pH or hypochlorhydria. Esophageal acid exposure was compared between the two groups. RESULTS:  The normal range for gastric pH was 0.3-2.9. The median age of the 1,582 patients was 51 years, and their median gastric pH was 1.7. Abnormal esophageal acid exposure was found in 797 patients (50.3%). Hypochlorhydria (resting gastric pH >2.9) was detected in 176 patients (11%). There was an inverse relationship between gastric pH and esophageal acid exposure (r = -0.13). For the patients with positive 24-h pH test results, the major effect of gastric pH was that the hypochlorhydric patients tended to have more reflux in the supine position than those with normal gastric pH. CONCLUSION:  There is an inverse, dose-dependent relationship between gastric pH and esophageal acid exposure. Negative 24-h esophageal pH test results for a patient with hypochlorhydria may prompt a search for nonacid reflux as the explanation for the patient's symptoms.

Day-to-day discrepancy in Bravo pH monitoring is related to the degree of deterioration of the lower esophageal sphincter and severity of reflux disease.
            (Ayazi et al., 2011) Download
BACKGROUND:  The Bravo capsule allows monitoring of esophageal acid exposure over a two-day period. Experience has shown that 24-32% of patients will have abnormal esophageal acid exposure detected on only one of the 2 days monitored. This variation has been explained by the effect of endoscopy and sedation. The aim of this study was to assess the day-to-day discrepancy following transnasal placement of the Bravo capsule without endoscopy or sedation and to determine factors related to this variability. METHODS:  Bravo pH monitoring was performed by transnasal placement of the capsule in 310 patients. Patients were divided into groups based on the composite pH score: both days normal, both days abnormal and only one of the 2 days abnormal. Lower esophageal sphincter (LES) characteristics were compared between groups. RESULTS:  Of the 310 patients evaluated, 60 (19%) showed a discrepancy between the 2 days. A total of 127 patients had a normal pH score on both days and 123 had an abnormal pH score on both days. Of the 60 patients with a discrepancy, 27 were abnormal the first day and 33 (55%) were abnormal the second day. Patients with abnormal esophageal acid exposure on both days had higher degrees of esophageal acid exposure and were more likely to have a defective LES compared to those with an abnormal score on only one day (35 vs. 83%, p=0.027). CONCLUSION:  Patients with a discrepancy between days of Bravo pH monitoring have lower esophageal acid exposure. Variability between the 2 days represents early deterioration of the gastroesophageal barrier and indicates less advanced reflux disease.

Iron nutrition.
            (Cook and Finch, 1975) Download
In view of the abundance of iron on this planet it is not surprising that this metal would be chosen for the critical function of oxygen transport. Elaborate systems regulating iron exchange with the environment and the transport of iron within the body have evolved. While these appear quite adequate for most animal species, there is reason to question their effectiveness in man. World-wide, iron lack is the commonest deficiency state encountered. In large segments of the population both the amount and availability of ingested iron is insufficient to replace the small quantities of iron normally lost. This review will attempt to clarify the nature of external iron exchange between man and his environment. Attention will be focused on the population at large rather than on pathologic mechanisms affecting iron metabolism

Gastric iron binding protein in iron chelation by gastric juice.
            (Davis et al., 1967) Download
The results of these experiments show that gastric juice is capable of  binding or chelating iron.


Impact of prolonged 48-h wireless capsule esophageal pH monitoring on diagnosis of gastroesophageal reflux disease and evaluation of the relationship between symptoms and reflux episodes.
            (Domingues et al., 2011) Download
CONTEXT:  Gastroesophageal reflux disease is one of the most common digestive diseases and an important cause of distress to patients. Diagnosis of this condition can require ambulatory pH monitoring. OBJECTIVES:  To determine the diagnostic yield of a wireless ambulatory pH monitoring system of 48-hours, recording to diagnose daily variability of abnormal esophageal acid exposure and its symptom association. METHODS:  A total of 100 consecutive patients with persistent reflux symptoms underwent wireless pH capsule placement from 2004 to 2009. The wireless pH capsule was deployed 5 cm proximal to the squamocolumnar junction after lower esophageal sphincter was manometrically determined. The pH recordings over 48-h were obtained after uploading data to a computer from the receiver that recorded pH signals from the wireless pH capsule. The following parameters were analyzed: (1) percentual time of distal esophageal acid exposure; (2) symptom association probability related to acid reflux. The results between the first and the second day were compared, and the diagnostic yield reached when the second day monitoring was included. RESULTS:  Successful pH data over 48-h was obtained in 95% of patients. Nearly one quarter of patients experienced symptoms ranging from a foreign body sensation to chest pain. Forty-eight hours pH data analysis was statistically significant when compared to isolated analysis of day 1 and day 2. Study on day 2 identified seven patients (30.4%) that would be missed if only day 1 was analyzed. Three patients (18.7%) out of 16 patients with normal esophageal acid exposure on both days, showed positive symptom association probability, which generated an increase in diagnostic yield of 43.4%. CONCLUSION:  Esophageal pH monitoring with wireless capsule is safe, well tolerated, does not require sedation. The extended 48-h period of study poses an increased yield to diagnose gastroesophageal reflux disease patients.

Upper gastrointestinal (GI) pH in young, healthy men and women.
            (Dressman et al., 1990) Download
The pH in the upper gastrointestinal tract of young, healthy men and women was measured in the fasting state and after administration of a standard solid and liquid meal. Calibrated Heidelberg capsules were used to record the pH continuously over the study period of approximately 6 hr. In the fasted state, the median gastric pH was 1.7 and the median duodenal pH was 6.1. When the meal was administered the gastric pH climbed briefly to a median peak value of 6.7, then declined gradually back to the fasted state value over a period of less than 2 hr. In contrast to the pH behavior in the stomach, feeding a meal caused a reduction in the median duodenal pH to 5.4. In addition, there was considerable fluctuation in the postprandial duodenal pH on an intrasubject basis. The pH in the duodenum did not return to fasted state values within the 4-hr postprandial observation period. There was no tendency for the duodenal pH to be related to the gastric pH in either the fed or fasted phases of the study. Furthermore, pH in the upper GI tract of young, healthy subjects appears to be independent of gender. The differences in upper GI pH between the fasted and the fed state are discussed in terms of dosage form performance and absorption for orally administered drugs.

Gastric acidity in older adults.
            (Hurwitz et al., 1997) Download
CONTEXT:  Early studies suggested that gastric acidity declines as people age. However, sequelae of achlorhydria are uncommon in older people, making this conventional wisdom unlikely. OBJECTIVE:  To ascertain the prevalence of basal gastric acidity and atrophic gastritis (indicated by serum pepsinogen ratio) in older adults. DESIGN:  Cross-sectional study in a volunteer sample. SETTING:  Retirement communities in suburbs of Kansas City, Mo. SUBJECTS:  A total of 248 white male and female volunteers aged 65 years or older living independently. MAIN OUTCOME MEASURES:  Presence of basal unstimulated gastric acid was evaluated noninvasively by having subjects swallow quininium resin. Gastric acid with a pH lower than 3.5 releases quinine, which is then absorbed and excreted into urine. Atrophic gastritis was defined as a ratio of serum pepsinogen I/pepsinogen II of less than 2.9. RESULTS:  Basal unstimulated gastric content was acidic (pH <3.5) in 208 (84%) of 248 elderly subjects. On retesting 66 subjects (35 normals and 31 hyposecretors), 28 (80%) of 35 had pH less than 3.5 both times, and 22 (71%) of 31 had pH of 3.5 or higher twice; in the remaining 16 subjects, low vs high gastric pH changed between tests. Weighted population prevalence estimates in this sample were 67% for consistent acid secretion, 22% for intermittent secretion, and 11% for consistent gastric pH higher than 3.5. Whereas 14 (67%) of 21 consistent hyposecretors had serum pepsinogen ratios of less than 2.9, indicating atrophic gastritis, only 2 (5%) of 44 consistent or intermittent secretors of acid had ratios in this range (P<.001). CONCLUSIONS:  In contrast to what is commonly stated, nearly 90% of elderly people in this study were able to acidify gastric contents, even in the basal, unstimulated state. Of those who were consistent hyposecretors of acid, most had serum markers of atrophic gastritis.


Fasting hypochlorhydria with gram positive gastric flora is highly prevalent in healthy old people
            (Husebye et al., 1992) Download
Fifteen healthy old people mean age 84 years (range 80-91 years), were examined to assess the effect of advanced age on the microecology of the upper gastrointestinal tract. Twelve of 15 (80%) were hypochlorhydric with pH 6.6 (0.3) (mean (SEM) and a mean bacterial count of 10(8) colony forming units (CFU) per ml (range 10(5)-10(10)) in fasting gastric aspirate. Normochlorhydric subjects had low counts (< or = 10(1) CFU/ml). The microbial flora was dominated by viridans streptococci, coagulase negative staphylococci, and Haemophilus sp. Only one subject harboured significant concentrations of Gram negative bacilli with Escherichia coli (10(4-5) CFU/ml) and Klebsiella (10(4-5)). Strict anaerobes were not found. The total concentration of short chain fatty acids in gastric aspirate was 10.6 (2.9) mmol/l (mean (SEM). Absence of significant, intraluminal fermentation of xylose to CO2 was shown by the 14C-d Xylose breath test, and ambulatory manometry showed preserved fasting motility pattern of the small intestine. Serum immunoglobulins were normal. Advanced age is accompanied by fasting hypochlorhydria and colonisation with mainly Gram positive flora in the upper gut. Other factors than old age and fasting hypochlorhydria are required for colonisation with Gram negative bacilli.

The iron-binding properties of gastric juice.
            (Jacobs and Miles, 1969) Download
Normal human gastric juice, hog stomach extract and intrinsic factor concentrate contain a high molecular weight substance, probably a mucoprotein, which binds iron and maintains it in a soluble form. The iron-binding capacity of gastric juice is inversely related to the secretory rate of the stomach. In iron deficiency anaemia the binding capacity is similar to that of non-anaemic subjects with comparable secretory rates.

The active role of vitamin C in mammalian iron metabolism: much more than just enhanced iron absorption
            (Lane and Richardson, 2014) Download
Ascorbate is a cofactor in numerous metabolic reactions. Humans cannot synthesize ascorbate owing to inactivation of the gene encoding the enzyme l-gulono-γ-lactone oxidase, which is essential for ascorbate synthesis. Accumulating evidence strongly suggests that in addition to the known ability of dietary ascorbate to enhance nonheme iron absorption in the gut, ascorbate within mammalian systems can regulate cellular iron uptake and metabolism. Ascorbate modulates iron metabolism by stimulating ferritin synthesis, inhibiting lysosomal ferritin degradation, and decreasing cellular iron efflux. Furthermore, ascorbate cycling across the plasma membrane is responsible for ascorbate-stimulated iron uptake from low-molecular-weight iron-citrate complexes, which are prominent in the plasma of individuals with iron-overload disorders. Importantly, this iron-uptake pathway is of particular relevance to astrocyte brain iron metabolism and tissue iron loading in disorders such as hereditary hemochromatosis and β-thalassemia. Recent evidence also indicates that ascorbate is a novel modulator of the classical transferrin-iron uptake pathway, which provides almost all iron for cellular demands and erythropoiesis under physiological conditions. Ascorbate acts to stimulate transferrin-dependent iron uptake by an intracellular reductive mechanism, strongly suggesting that it may act to stimulate iron mobilization from the endosome. The ability of ascorbate to regulate transferrin iron uptake could help explain the metabolic defect that contributes to ascorbate-deficiency-induced anemia.

Common features of patients with autoimmune atrophic gastritis
            (Miceli et al., 2012) Download
BACKGROUND & AIMS: Autoimmune atrophic gastritis (AIG) is characterized by immune-mediated chronic inflammation of the gastric body and fundus, leading to hypo-achlorhydria and vitamin B12 deficiency. We analyzed the clinical features of AIG and sought to identify factors that might be used in diagnosis. METHODS: We collected and analyzed clinical data from 99 consecutive patients (age, 59 +/- 17 y) who were diagnosed with AIG, based on histologic factors and the presence of autoantibodies against gastric parietal cells. RESULTS: Clinical factors that led to a diagnosis of AIG included hematologic findings related to vitamin B12 deficiency (n = 37), incidental histologic evidence in gastric biopsy specimens (n = 34), immune disorders (n = 18; 9 were celiac disease), neurologic symptoms (n = 6), and a family history of AIG (n = 4). CONCLUSIONS: Based on an analysis of 99 consecutive patients with AIG, this disorder is not solely a condition of the elderly. Other features to look for in making a diagnosis of AIG include vitamin B12 deficiency, histologic factors, and immune disorders.

Studies on an iron-binding component in human gastric juice.
            (Morgan et al., 1969) Download
Evidence has been furnished confirming the presence of an iron-binding component gastroferrin, in human gastric juice.


Assessment of gastric acidity of Japanese subjects over the last 15 years.
            (Morihara et al., 2001) Download
The gastric acidity of young to elderly Japanese subjects from 1989 to 1999 was assessed and compared with that obtained in 1984, using GA-Test capsules containing acid-dissolving granules of riboflavin. The percentage of achlorhydric subjects increased with age as observed before, however, an over all decrease in all age categories year by year was noted. The percentage of achlorhydric subjects aged 50 years in 1995-1999 was about 40%, which was lower than that (60%) in 1984. However, such a chronological change was not observed when the percentage of achlorhydric subjects was determined according to birth year, indicating that it is related to the birth year of subjects. The percentage of achlorhydric subjects correlated with infection by Helicobacter pylori. Considering the high percentage of achlorhydric elderly, bioavailability and bioequivalence studies should be performed taking into consideration the effects of gastric acidity on the in vivo performance of drug products.

Autoimmune atrophic gastritis--pathogenesis, pathology and management.
            (Neumann et al., 2013) Download
Autoimmune gastritis is a chronic progressive inflammatory condition that results in the replacement of the parietal cell mass by atrophic and metaplastic mucosa. A complex interaction of autoantibodies against the parietal cell proton pump and sensitized T cells progressively destroy the parietal cells, inducing hypochlorhydria and then achlorhydria, while autoantibodies against the intrinsic factor impair the absorption of vitamin B₁₂. The resulting cobalamin deficiency manifests with megaloblastic anaemia and neurological and systemic signs and symptoms collectively known as pernicious anaemia. Previously believed to be predominantly a disease of elderly women of Northern European ancestry, autoimmune gastritis has now been recognized in all populations and ethnic groups, but because of the complexity of the diagnosis no reliable prevalence data are available. For similar reasons, as well as the frequent and often unknown overlap with Helicobacter pylori infection, the risk of gastric cancer has not been adequately assessed in these patients. This Review summarizes the epidemiology, pathogenesis and pathological aspects of autoimmune metaplastic atrophic gastritis. We also provide practical advice for the diagnosis and management of patients with this disease.


Achlorhydria; associated symptoms and response to hydrochloric acid.
            (Rappaport, 1955) Download
Dilut hydrochloric acid was prescribed. Twelve patients were substituded with Acidulin (glutamin acid hypochloride). Relatively few continued since it did not relieve the primary complaints.

Chronic urticaria associated with hypochlorhydria or achlorhydria.
            (Rawls and Ancona, 1951) Download
Chronic urticaria is frequently associated with hypochlorhydria or achlorhydria. A gastric analysis is a simple procdure and should be done more often.

Wireless pH capsule--yield in clinical practice.
            (Roman et al., 2012) Download
Wireless pH monitoring is one of the recent technologies that focus on improving the diagnosis of gastroesophageal reflux disease (GERD). The capsule, which is fixed within the esophagus, transmits data via telemetry to an external receiver. The capsule is usually inserted 6 cm above the squamocolumnar junction during an upper endoscopy. The standard recording duration is 48 hours but this can be extended to 96 hours. The wireless capsule has been shown to be at least as accurate as the conventional catheter for the monitoring of esophageal pH. Normal pH values have been established in three different series. The use of a wireless capsule provides an increased diagnostic yield for GERD compared with the conventional catheter. The increased yield is the result of higher sensitivity to detect both abnormal acid esophageal exposure and positive symptom-reflux association. This may be related both to the prolonged recording duration and to fewer dietary modifications and restrictions on activities. Several studies have shown that the pH capsule was better tolerated by patients than the conventional pH catheter. Mild-to-moderate chest pain represents the main side effect of the pH capsule: severe chest pain requiring endoscopic removal of the capsule is rare. The main indication for wireless capsule application is monitoring of distal esophageal pH for diagnostic purpose, particularly in patients with a normal endoscopic examination. The capsule technique has some limitations: costs are higher than conventional pH monitoring, misplacement may occur, and the sampling rate is lower. Finally, compared with pH-impedance monitoring, only acid reflux events can be evaluated.


Iron-binding component in human gastric juice.
            (Rudzki and Deller, 1969) Download
Dr. Morgan and his colleagues (April 26, p. 861) have confirmed our observations on the presence of an iron-binding component, gastroferrin, in human gastric juice. It is likely that gastroferrin is a glycoprotein.

Rosacea: With A Study Of Accompanying Conditions.
            (Rulison, 1927) Download
Reference to textbooks on dermatology discloses a consensus of opinion that rosacea is commonly associated with derangement of the gastrointestinal tract. Complete gastrointestinal examinations were made on 50 patients suffering from rosacea. Two-thirds of them were found to have a group of functional abnormalities grouped as follows: A neurotic tendency, subnormal weight, low blood pressure, poor muscle tone, faulty posture, visceroptosis, chronic constipation, spasticity of the large bowel, and gastric subacidity.

Upper gastrointestinal pH in seventy-nine healthy, elderly, North American men and women.
            (Russell et al., 1993) Download
Gastric and duodenal pH levels were measured in 79 healthy, elderly men and women (mean +/- SD = 71 +/- 5 years) under both fasted and fed conditions using the Heidelberg capsule technique. The pH was recorded for 1 hr in the fasted state, a standard liquid and solid meal of 1000 cal was given over 30 min, then the pH was measured for 4 hr postprandially. Results are given as medians and interquartile ranges: fasted gastric pH, 1.3 (1.1-1.6); gastric pH during the meal, 4.9 (3.9-5.5); fasted duodenal pH, 6.5 (6.2-6.7); and duodenal pH during the meal, 6.5 (6.4-6.7). Although fasted gastric pH, fasted duodenal pH, and duodenal pH during the meal differ statistically from those observed in young subjects, the differences are not expected to be clinically significant in terms of drug absorption for the majority of elderly subjects. Following a meal, gastric pH decreased from a peak pH of 6.2 (5.8-6.7) to pH 2.0 within 4 hr in most subjects. This rate of return was considerably slower than in young, healthy subjects. Nine subjects (11%) had a median fasted gastric pH > 5.0, and in five of these subjects the median pH remained > 5.0 postprandially. In this group, drugs and dosage forms which require an acidic environment for dissolution or release may be poorly assimilated.


Significant association of deficiency of hemoglobin, iron and vitamin B12, high homocysteine level, and gastric parietal cell antibody positivity with atrophic glossitis.
            (Sun et al., 2012) Download
BACKGROUND:  Atrophic glossitis (AG) is considered to be a marker of nutritional deficiency. In this study, we evaluated whether there was an intimate association of the deficiency of hemoglobin, iron, vitamin B12 or folic acid, high blood homocysteine level, and serum gastric parietal cell antibody (GPCA) positivity with AG. METHODS:  The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations and the serum GPCA level in 176 AG patients were measured and compared with the corresponding levels in 176 age- and sex-matched healthy control subjects. RESULTS:  We found that 39 (22.2%), 47 (26.7%), 13 (7.4%), and 3 (1.7%) AG patients had deficiencies of Hb (men < 13 g/dl, women < 12 g/dl), iron (<60 μg/dl), vitamin B12 (<200 pg/ml), and folic acid (<4 ng/ml), respectively. Moreover, 38 (21.6%) AG patients had abnormally high blood homocysteine level, and 47 (26.7%) AG patients had serum GPCA positivity. AG patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency, of abnormally elevated blood homocysteine level, or of serum GPCA positivity than healthy control subjects (all P-values = 0.000). However, no significant difference in frequency of folic acid deficiency was found between AG patients and healthy control subjects. CONCLUSION:  We conclude that there is a significant association of deficiency of hemoglobin, iron and vitamin B12, abnormally high blood homocysteine level, and serum GPCA positivity with AG.

Gastric Reacidification with Betaine HCl in Healthy Volunteers with Rabeprazole-Induced Hypochlorhydria
            (Yago et al., 2013) Download
Previous studies have demonstrated that increased gastric pH from the use of acid-reducing agents, such as proton-pump inhibitors or H2-receptor antagonists, can significantly impact the absorption of weakly basic drugs that exhibit pH-dependent solubility. Clinically practical strategies to mitigate this interaction have not been developed. This pilot study evaluated the extent and time course of gastric reacidification after a solid oral dosage form of anhydrous betaine HCl in healthy volunteers with pharmacologically induced hypochlorhydria. Six healthy volunteers with baseline normochlorhydria (fasting gastric pH < 4) were enrolled in this single period study. Hypochlorhydria was induced via 20 mg oral rabeprazole twice daily for four days. On the fifth day, an additional 20 mg dose of oral rabeprazole was given and gastric pH was monitored continuously using the Heidelberg pH capsule. After gastric pH > 4 was confirmed for 15 min, 1500 mg of betaine HCl was given orally with 90 mL of water and gastric pH was continuously monitored for 2 h. Betaine HCl significantly lowered gastric pH by 4.5 (+/-0.5) units from 5.2 (+/-0.5) to 0.6 (+/-0.2) (P < 0.001) during the 30 min interval after administration. The onset of effect of betaine HCl was rapid, with a mean time to pH < 3 of 6.3 (+/-4.3) min. The reacidification period was temporary with a gastric pH < 3 and < 4 lasting 73 (+/-33) and 77 (+/-30) min, respectively. Betaine HCl was well tolerated by all subjects. In healthy volunteers with pharmacologically induced hypochlorhydria, betaine HCl was effective at temporarily lowering gastric pH. The rapid onset and relatively short duration of gastric pH reduction gives betaine HCl the potential to aid the absorption of orally administered weakly basic drugs that exhibit pH-dependent solubility when administered under hypochlorhydric conditions.




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