 | This article needs additional citations for verification .(February 2013) |
| Achlorhydria | |
|---|---|
| Other names | Hypochlorhydria |
 | |
| Hydrogen chloride (major component of gastric acid) | |
| Pronunciation | |
| Specialty | Internal medicine |
Achlorhydria and hypochlorhydria refer to states where the production of hydrochloric acid in gastric secretions of the stomach and other digestive organs is absent or low, respectively. [1] It is associated with various other medical problems.
Irrespective of the cause, achlorhydria can result as known complications of bacterial overgrowth and intestinal metaplasia and symptoms are often consistent with those diseases:
Since acidic pH facilitates the absorption of iron, achlorhydric patients often develop iron deficiency anemia. The acidic environment of stomach helps conversion of pepsinogen into pepsin, which is highly important in digesting the protein into smaller components, such as a complex protein into simple peptides and amino acids inside the stomach, which are later absorbed by the gastrointestinal tract.
Bacterial overgrowth and B12 deficiency (pernicious anemia) can cause micronutrient deficiencies that result in various clinical neurological manifestations, including visual changes, paresthesias, ataxia, limb weakness, gait disturbance, memory defects, hallucinations and personality and mood changes.
Risk of particular infections, such as Vibrio vulnificus (commonly from seafood) is increased. Even without bacterial overgrowth, low stomach acid (high pH) can lead to nutritional deficiencies through decreased absorption of basic electrolytes (magnesium, zinc, etc.) and vitamins (including vitamin C, vitamin K, and the B complex of vitamins). Such deficiencies may be involved in the development of a wide range of pathologies, from fairly benign neuromuscular issues to life-threatening diseases.
Prevalence
Achlorhydria is present in about 2.5% of the population under 60 years old and about 5% of the population over 60 years old. [5] The incidence increases to around 12% in populations over 80 years old. An absence of hydrochloric acid increases with advancing age. A lack of hydrochloric acid produced by the stomach is one of the most common age-related causes of a harmed digestive system. [6]
Among men and women, 27% experience a varying degree of achlorhydria. US researchers found that over 30% of women and men over the age of 60 have little to no acid secretion in the stomach. Additionally, 40% of postmenopausal women have shown to have no basal gastric acid secretion in the stomach, with 39.8% occurring in females 80 to 89 years old. [6]
Comorbidities
Autoimmune disorders are also linked to advancing age, specifically autoimmune gastritis, which is when the body produces unwelcomed antibodies and causes inflammation of the stomach. [5] Autoimmune disorders are also a cause for small bacterial growth in the bowel and a deficiency of Vitamin B-12. These have also proved to be factors of acid secretion in the stomach. [7] Autoimmune conditions can often be managed with various treatments; however, little is known about how or if these treatments effect achlorhydria. [5]
Thyroid hormones can contribute to changes in the level of hydrochloric acid in the stomach. Hypothyroidism is associated with a greater risk of developing achlorhydria. [5]
Long term usage of medications or drugs
Extended use of anti-acids, antibiotics, and other drugs can contribute to hypochlorhydria. Proton pump inhibitors (PPIs) are very commonly used to temporarily relieve symptoms conditions such as gastroesophageal reflux and peptic ulcers. [7] Risk increases as these drugs are taken over a longer time period, often many years, typically beyond the recommended therapeutic usage.
Stress can also be linked to symptoms associated with achlorhydria including constant belching, constipation, and abdominal pain. [7]
For practical purposes, gastric pH and endoscopy should be done in someone with suspected achlorhydria. Older testing methods using fluid aspiration through a nasogastric tube can be done, but these procedures can cause significant discomfort and are less efficient ways to obtain a diagnosis.
A complete 24-hour profile of gastric acid secretion is best obtained during an esophageal pH monitoring study.
Achlorhydria may also be documented by measurements of extremely low levels of pepsinogen A (PgA) (< 17 µg/L) in blood serum. The diagnosis may be supported by high serum gastrin levels (> 500–1000 pg/mL). [8]
The "Heidelberg test" is an alternative way to measure stomach acid and diagnose hypochlorhydria/achlorhydria.
A check can exclude deficiencies in iron, calcium, prothrombin time, vitamin B-12, vitamin D, and thiamine. Complete blood count with indices and peripheral smears can be examined to exclude anemia. Elevation of serum folate is suggestive of small bowel bacterial overgrowth. Bacterial folate can be absorbed into the circulation.
Once achlorhydria is confirmed, a hydrogen breath test can check for bacterial overgrowth.
Treatment focuses on addressing the underlying cause of symptoms.
Treatment of gastritis that leads to pernicious anemia consists of parenteral vitamin B-12 injection. Associated immune-mediated conditions (e.g., insulin-dependent diabetes mellitus, autoimmune thyroiditis) should also be treated. However, treatment of these disorders has no known effect in the treatment of achlorhydria.
Achlorhydria associated with Helicobacter pylori infection may respond to H. pylori eradication therapy, although resumption of gastric acid secretion may only be partial and it may not always reverse the condition completely. [9]
Antimicrobial agents, including metronidazole, amoxicillin/clavulanate potassium, ciprofloxacin, and rifaximin, can be used to treat bacterial overgrowth.
Achlorhydria resulting from long-term proton-pump inhibitor (PPI) use may be treated by dose reduction or withdrawal of the PPI.
Little is known on the prognosis of achlorhydria, although there have been reports of an increased risk of gastric cancer. [10]
A 2007 review article noted that non-Helicobacter bacterial species can be cultured from achlorhydric (pH > 4.0) stomachs, whereas normal stomach pH only permits the growth of Helicobacter species. Bacterial overgrowth may cause false-positive H. pylori test results due to the change in pH from urease activity. [11]
Small bowel bacterial overgrowth is a chronic condition. Retreatment may be necessary once every 1–6 months. [12] Prudent use of antibacterials now calls for an antimicrobial stewardship policy to manage antibiotic resistance. [13]
Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase proton pump.
Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines is a duodenal ulcer. The most common symptoms of a duodenal ulcer are waking at night with upper abdominal pain, and upper abdominal pain that improves with eating. With a gastric ulcer, the pain may worsen with eating. The pain is often described as a burning or dull ache. Other symptoms include belching, vomiting, weight loss, or poor appetite. About a third of older people have no symptoms. Complications may include bleeding, perforation, and blockage of the stomach. Bleeding occurs in as many as 15% of cases.
Heartburn, also known as pyrosis, cardialgia or acid indigestion, is a burning sensation in the central chest or upper central abdomen. Heartburn is usually due to regurgitation of gastric acid into the esophagus. It is the major symptom of gastroesophageal reflux disease (GERD).
Helicobacter pylori, previously known as Campylobacter pylori, is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape is thought to have evolved in order to penetrate the mucoid lining of the stomach and thereby establish infection. The bacterium was first identified in 1982 by the Australian doctors Barry Marshall and Robin Warren. H. pylori has been associated with cancer of the mucosa-associated lymphoid tissue in the stomach, esophagus, colon, rectum, or tissues around the eye, and of lymphoid tissue in the stomach.
Intrinsic factor (IF), cobalamin binding intrinsic factor, also known as gastric intrinsic factor (GIF), is a glycoprotein produced by the parietal cells (in humans) or chief cells (in rodents) of the stomach. It is necessary for the absorption of vitamin B12 later on in the distal ileum of the small intestine. In humans, the gastric intrinsic factor protein is encoded by the CBLIF gene. Haptocorrin (transcobalamin I) is another glycoprotein secreted by the salivary glands which binds to vitamin B12. Vitamin B12 is acid-sensitive and in binding to haptocorrin it can safely pass through the acidic stomach to the duodenum.
Barry James Marshall is an Australian physician, Nobel Prize Laureate in Physiology or Medicine, Professor of Clinical Microbiology and Co-Director of the Marshall Centre at the University of Western Australia. Marshall and Robin Warren showed that the bacterium Helicobacter pylori plays a major role in causing many peptic ulcers, challenging decades of medical doctrine holding that ulcers were caused primarily by stress, spicy foods, and too much acid. This discovery has allowed for a breakthrough in understanding a causative link between Helicobacter pylori infection and stomach cancer.
Pernicious anemia is a disease in which not enough red blood cells are produced due to a deficiency of vitamin B12. Those affected often have a gradual onset. The most common initial symptoms are feeling tired and weak. Other symptoms of anemia may include shortness of breath, lightheadedness, headaches, sore red tongue, cold hands and feet, pale or yellow skin, chest pain, and an irregular heartbeat. The digestive tract may also be disturbed giving symptoms that can include nausea and vomiting, heartburn, upset stomach and loss of appetite. Symptoms of vitamin B12 deficiency may include decreased ability to think, numbness in the hands and feet, memory problems, blurred vision, trouble walking, poor balance, muscle weakness, decreased smell and taste, poor reflexes, clumsiness, depression, and confusion. Without treatment, some of these problems may become permanent.
Gastric acid, gastric juice, or stomach acid is a digestive fluid formed within the stomach lining. With a pH between 1 and 3, gastric acid plays a key role in digestion of proteins by activating digestive enzymes, which together break down the long chains of amino acids of proteins. Gastric acid is regulated in feedback systems to increase production when needed, such as after a meal. Other cells in the stomach produce bicarbonate, a base, to buffer the fluid, ensuring a regulated pH. These cells also produce mucus – a viscous barrier to prevent gastric acid from damaging the stomach. The pancreas further produces large amounts of bicarbonate and secretes bicarbonate through the pancreatic duct to the duodenum to neutralize gastric acid passing into the digestive tract.
Parietal cells (also known as oxyntic cells) are epithelial cells in the stomach that secrete hydrochloric acid (HCl) and intrinsic factor. These cells are located in the gastric glands found in the lining of the fundus and body regions of the stomach. They contain an extensive secretory network of canaliculi from which the HCl is secreted by active transport into the stomach. The enzyme hydrogen potassium ATPase (H+/K+ ATPase) is unique to the parietal cells and transports the H+ against a concentration gradient of about 3 million to 1, which is the steepest ion gradient formed in the human body. Parietal cells are primarily regulated via histamine, acetylcholine and gastrin signalling from both central and local modulators.
A gastrectomy is a partial or total surgical removal of the stomach.
Rabeprazole, sold under the brand name Aciphex, among others, is a medication that decreases stomach acid. It is used to treat peptic ulcer disease, gastroesophageal reflux disease, and excess stomach acid production such as in Zollinger–Ellison syndrome. It may also be used in combination with other medications to treat Helicobacter pylori. Effectiveness is similar to other proton pump inhibitors (PPIs). It is taken by mouth.
Gastritis is inflammation of the lining of the stomach. It may occur as a short episode or may be of a long duration. There may be no symptoms but, when symptoms are present, the most common is upper abdominal pain. Other possible symptoms include nausea and vomiting, bloating, loss of appetite and heartburn. Complications may include stomach bleeding, stomach ulcers, and stomach tumors. When due to autoimmune problems, low red blood cells due to not enough vitamin B12 may occur, a condition known as pernicious anemia.
Gastrointestinal diseases refer to diseases involving the gastrointestinal tract, namely the esophagus, stomach, small intestine, large intestine and rectum, and the accessory organs of digestion, the liver, gallbladder, and pancreas.
Atrophic gastritis is a process of chronic inflammation of the gastric mucosa of the stomach, leading to a loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues. As a result, the stomach's secretion of essential substances such as hydrochloric acid, pepsin, and intrinsic factor is impaired, leading to digestive problems. The most common are vitamin B12 deficiency possibly leading to pernicious anemia; and malabsorption of iron, leading to iron deficiency anaemia. It can be caused by persistent infection with Helicobacter pylori, or can be autoimmune in origin. Those with autoimmune atrophic gastritis (Type A gastritis) are statistically more likely to develop gastric carcinoma, Hashimoto's thyroiditis, and achlorhydria.
Gastrinomas are neuroendocrine tumors (NETs), usually located in the duodenum or pancreas, that secrete gastrin and cause a clinical syndrome known as Zollinger–Ellison syndrome (ZES). A large number of gastrinomas develop in the pancreas or duodenum, with near-equal frequency, and approximately 10% arise as primary neoplasms in lymph nodes of the pancreaticoduodenal region.
Blind loop syndrome, also known as stagnant loop syndrome, is a state that occurs when the normal bacterial flora of the small intestine proliferates to numbers that cause significant derangement to the normal physiological processes of digestion and absorption. In some cases of blind loop syndrome, overgrowth of pathogenic non-commensal bacteria has also been noted. It has long been understood that from birth, and throughout life, large amounts of bacteria reside symbiotically within animal gastrointestinal tracts such as the human gastrointestinal tract. The understanding of this gut flora has even led to novel treatments for bowel irregularity that utilize so called "probiotics" or good bacteria that aid in normal digestion. The problem of blind loop syndrome arises when the bacterial colonies residing in the upper gastrointestinal tract begin to grow out of control or are altered in their makeup thereby creating a burden on the normal physiological processes occurring in the small intestine. This results in problems, among others, of: vitamin B12 deficiency, fat malabsorption and steatorrhea, fat-soluble vitamin deficiencies and intestinal wall injury.
Gastric outlet obstruction (GOO) is a medical condition where there is an obstruction at the level of the pylorus, which is the outlet of the stomach. Individuals with gastric outlet obstruction will often have recurrent vomiting of food that has accumulated in the stomach, but which cannot pass into the small intestine due to the obstruction. The stomach often dilates to accommodate food intake and secretions. Causes of gastric outlet obstruction include both benign causes, as well as malignant causes, such as gastric cancer.
This is a timeline of the events relating to the discovery that peptic ulcer disease and some cancers are caused by H. pylori. In 2005, Barry Marshall and Robin Warren were awarded the Nobel Prize in Physiology or Medicine for their discovery that peptic ulcer disease (PUD) was primarily caused by Helicobacter pylori, a bacterium with affinity for acidic environments, such as the stomach. As a result, PUD that is associated with H. pylori is currently treated with antibiotics used to eradicate the infection. For decades prior to their discovery, it was widely believed that PUD was caused by excess acid in the stomach. During this time, acid control was the primary method of treatment for PUD, to only partial success. Among other effects, it is now known that acid suppression alters the stomach milieu to make it less amenable to H. pylori infection.
Stomach diseases include gastritis, gastroparesis, Crohn's disease and various cancers.
The Heidelberg test is a medical diagnostic test used in the diagnosis of hypochlorhydria, i.e. insufficient hydrochloric acid in the stomach, hyperchlorhydria, achlorhydria, and for suspected bile reflux.