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Query: What is the pH of the human stomach's acid?
The main constituent of gastric acid is hydrochloric acid which is produced by parietal cells (also called oxyntic cells) in the gastric glands in the stomach. Its secretion is a complex and relatively energetically expensive process. Parietal cells contain an extensive secretory network (called canaliculi) from which the hydrochloric acid is secreted into the lumen of the stomach. The pH of gastric acid is 1.5 to 3.5[1] in the human stomach lumen, the acidity being maintained by the proton pump H+/K+ ATPase. The parietal cell releases bicarbonate into the bloodstream in the process, which causes a temporary rise of pH in the blood, known as an alkaline tide.
In the human digestive system, a bolus (a small rounded mass of chewed up food) enters the stomach through the oesophagus via the lower oesophageal sphincter. The stomach releases proteases (protein-digesting enzymes such as pepsin) and hydrochloric acid, which kills or inhibits bacteria and provides the acidic pH of 2 for the proteases to work. Food is churned by the stomach through muscular contractions of the wall called peristalsis – reducing the volume of the bolus, before looping around the fundus and the body of stomach as the boluses are converted into chyme (partially digested food). Chyme slowly passes through the pyloric sphincter and into the duodenum of the small intestine, where the extraction of nutrients begins. Depending on the quantity and contents of the meal, the stomach will digest the food into chyme within anywhere between forty minutes and a few hours . The average human stomach can comfortably hold about a litre of food.
A typical adult human stomach will secrete about 1.5 liters of gastric acid daily.[2] Gastric acid secretion happens in several steps. Chloride and hydrogen ions are secreted separately from the cytoplasm of parietal cells and mixed in the canaliculi. Gastric acid is then secreted into the lumen of the gastric gland and gradually reaches the main stomach lumen.[2] The exact manner in which the secreted acid reaches the stomach lumen is controversial, as acid must first cross the relatively pH neutral gastric mucus layer.
The charge of a molecule depends upon the pH of its solution. In an acidic medium, basic drugs are more charged and acidic drugs are less charged. The converse is true in a basic medium. For example, Naproxen is a non-steroidal anti-inflammatory drug that is a weak acid (its pKa value is 5.0). The gastric juice has a pH of 2.0. It is a three-fold difference (due to log scale) between its pH and its pKa; therefore there is a 1000× difference between the charged and uncharged concentrations. So, in this case, for every one molecule of charged Naproxen, there are 1000 molecules of uncharged Naproxen at a pH of 2. This is why weak acids are better absorbed from the stomach and weak bases from intestine where the pH is alkaline. When pH of a solution is equal to pKa of dissolved drug, then 50% of the drug is ionized, another 50% is unionized. This is described by the Henderson-Hasselbalch equation.
Pepsin is the main gastric enzyme. It is produced by the stomach cells called "chief cells" in its inactive form pepsinogen, which is a zymogen. Pepsinogen is then activated by the stomach acid into its active form, pepsin. Pepsin breaks down the protein in the food into smaller particles, such as peptide fragments and amino acids. Protein digestion, therefore, primarily starts in the stomach, unlike carbohydrate and lipids, which start their digestion in the mouth (however, trace amounts of the enzyme kallikrein, which catabolises certain protein, is found in saliva in the mouth). Gastric lipase: Gastric lipase is an acidic lipase secreted by the gastric chief cells in the fundic mucosa in the stomach. It has a pH optimum of 3–6. Gastric lipase, together with lingual lipase, comprise the two acidic lipases. These lipases, unlike alkaline lipases (such as pancreatic lipase), do not require bile acid or colipase for optimal enzymatic activity. Acidic lipases make up 30% of lipid hydrolysis occurring during digestion in the human adult, with gastric lipase contributing the most of the two acidic lipases. In neonates, acidic lipases are much more important, providing up to 50% of total lipolytic activity.
Discovered in 1836, pepsin was one of the first enzymes to be classified as an exoenzyme. The enzyme is first made in the inactive form, pepsinogen by chief cells in the lining of the stomach. With an impulse from the vagus nerve, pepsinogen is secreted into the stomach, where it mixes with hydrochloric acid to form pepsin. Once active, pepsin works to break down proteins in foods such as dairy, meat, and eggs. Pepsin works best at the pH of gastric acid, 1.5 to 2.5, and is deactivated when the acid is neutralized to a pH of 7.
Gastric lipase is an acidic lipase secreted by the gastric chief cells in the fundic mucosa in the stomach. It has a pH optimum of 3–6. Gastric lipase, together with lingual lipase, comprise the two acidic lipases. These lipases, unlike alkaline lipases (such as pancreatic lipase), do not require bile acid or colipase for optimal enzymatic activity. Acidic lipases make up 30% of lipid hydrolysis occurring during digestion in the human adult, with gastric lipase contributing the most of the two acidic lipases. In neonates, acidic lipases are much more important, providing up to 50% of total lipolytic activity.They breakdown triglycerides into monoglycerides and fatty acids.
Most enteric coatings work by presenting a surface that is stable at the intensely acidic pH found in the stomach, but breaks down rapidly at a higher pH (alkaline pH). For example, they will not dissolve in the gastric acids of the stomach (pH ~3), but they will in the alkaline (pH 7–9) environment present in the small intestine. The time required for an enteric-coated dosage form to reach the intestine mostly depends on the presence and type of food in the stomach. It varies from 30 minutes up to 7 hours, with an average time of 6 hours. Although some studies indicated that larger sized dosage forms may require additional time for gastric emptying, others suggested that the size, shape, or volume of the tablet possess no significant effects instead. Enteric coated granules emptying rate is, however, less affected by the presence of food and present the more uniform release and reproducible transit time typical of the multiparticulates dispersion.
Besides, indometacin has logarithmic acid dissociation constant pKa of 3 to 4.5. Since the physiologic body pH is well above the pKa range of indometacin, most of the indometacin molecules will be disscociated into ionised form, leaving very little unionised form of indometacin to cross a cell membrane. If the pH gradient across a cell membrane is high, most of the indometacin molecules will be trapped in one side of the membrane with higher pH. This phenomenon is called "ion trapping". The phenomenon of ion trapping is particularly prominent in the stomach as pH at the stomach mucosa layer is extremely acidic, while the parietal cells are more alkaline. Therefore, indometacin are trapped inside the parietal cells in ionised form, damaging the stomach cells, causing stomach irritation. This stomach irritation can reduce if the stomach acid pH is reduced.
In the case of "Salmonella" a relatively large inoculum of 1 million to 1 billion organisms is necessary to produce symptoms in healthy human volunteers, as "Salmonellae" are very sensitive to acid. An unusually high stomach pH level (low acidity) greatly reduces the number of bacteria required to cause symptoms by a factor of between 10 and 100.
Gastric acid is one of the main secretions of the stomach. It consists mainly of hydrochloric acid and acidifies the stomach content to a pH of 1 to 2.
Rabeprazole's mechanism of action first involves getting absorbed into the parietal cells of the stomach, which are the cells that are responsible for secreting hydrochloric acid (HCl). At this point, rabeprazole is inactive. However, rabeprazole is then secreted into the secretory canaliculus of the parietal cells, which is the space from which acid secretion occurs. Here, acid secretion is mediated by the energy-dependent acid pumps, called hydrogen potassium adenosine triphosphatase (H/K ATPase) pumps. These enzymatic pumps have cysteine amino acid residues. After being activated by gastric (stomach) acid to a reactive sulfenamide intermediate, rabeprazole permanently binds the cysteine residues, forming covalent, disulfide bonds. This action fundamentally alters the configuration of the acid pump, thereby inhibiting its activity. Thus, acid can no longer be secreted into the gastric lumen (the empty space of the stomach), and the pH of the stomach increases (decrease in the concentration of hydrogen ions, H). Due to the permanent inhibition of the individual proton pump that each molecule of rabeprazole has bound to, acid secretion is effectively suppressed until new proton pumps are produced by the parietal cells.
The highest concentration that gastric acid reaches in the stomach is 160 mM in the canaliculi. This is about 3 million times that of arterial blood, but almost exactly isotonic with other bodily fluids. The lowest pH of the secreted acid is 0.8,[3] but the acid is diluted in the stomach lumen to a pH between 1 and 3.
The acid gives carbonated water a slightly tart flavor. The pH level between 3 and 4 is approximately in between apple juice and orange juice in acidity, but much less acidic than the acid in the stomach. A normal, healthy human body maintains pH equilibrium via acid–base homeostasis and will not be materially adversely affected by consumption of plain carbonated water. Alkaline salts, such as sodium bicarbonate, potassium bicarbonate, or potassium citrate, will increase pH.
The ionic charges of mucin are mainly provided by acidic amino acids including aspartic acid (pKa=3.9) and glutamic acid (pKa=4.2). The charges of acidic amino acids will change with environmental pH value due to acid dissociation and association. Aspartic acid, for example, has a negative side chain when the pH value is above 3.9, while a neutrally charged side chain will be introduced as pH value drops below 3.9. Thus, the number of negative charges in mucus is influenced by the pH value of surrounding environment. That is, the polyelectrolyte effect of mucus is largely affected by the pH value of solution due to the charge variation of acidic amino acid residues on the mucin backbone. For instance, the charged residue on mucin is protonated at a normal pH value of the stomach, approximately pH 2. In this case, there is scarcely polyelectrolyte effect, thereby causing compact mucus with little swelling capacity. However, a kind of bacteria, "Helicobacter pylori", is prone to producing base to elevate the pH value in stomach, leading to the deprotonation of aspartic acids and glutamic acids, i.e., from neutral to negative-charged. The negative charges in the mucus greatly increase, thus inducing the polyelectrolyte effect and the swelling of the mucus. This swelling effect increases the pore size of the mucus and decreases mucus' viscosity, which allows bacteria to penetrate and migrate into the mucus and cause disease.
The enterochromaffin-like cells store and release histamine when the pH of the stomach becomes too high. The release of histamine is stimulated by the secretion of gastrin from the G cells. Histamine promotes the production and release of bicarbonate ions from the parietal cells to the blood and protons to the stomach lumen. When the stomach pH decreases(becomes more acidic), the ECLs stop releasing histamine.
Bicarbonate also serves much in the digestive system. It raises the internal pH of the stomach, after highly acidic digestive juices have finished in their digestion of food. Bicarbonate also acts to regulate pH in the small intestine. It is released from the pancreas in response to the hormone secretin to neutralize the acidic chyme entering the duodenum from the stomach.
A buffering agent can be either a weak acid or weak base. Buffering agents are usually added to water to form a buffer solution, which only slightly changes its pH in response to other acids and bases being combined with it, particularly a strong acid or a strong base. Another example is buffered aspirin which has a buffering agent, such as MgO or CaCO, that will help maintain the balance between the acid H-A (protonated) and the salt A (deprotonated) forms of aspirin as it passes through the acidic stomach of the patient. The H-A form of aspirin is a covalent molecule and is more absorbed by the stomach lining, leading to irritation. The antacid properties of these buffering agents help to maintain the balance toward the salt form by reducing the amount of stomach acid (HCl) which protonates the salt form, A.
The Heidelberg Diagnostic test is used to diagnose Hypochlorhydria (reduced acid production), Hyperchlorhydria (excessive acid production), Achlorhydria (no acid production), Pyloric Insufficiency, Heavy Stomach Mucus (from infection or ulceration), Acute and Sub-acute Gastritis. The test will also allow the physician to observe peristaltic activity, delayed and marked delayed emptying of the stomach (Gastroparesis) and dumping syndrome. The test is an in-office procedure that does not require the use of a catheter, or sedation. During testing the patient is relaxed and comfortable, without the trauma associated with other procedures. There are two methods of testing with the pH capsule. The first method requires the use of a fine medical grade thread (tether)that is attached to the capsule, so that it can be suspended in the stomach for extended testing of the stomachs parietal cells. Testing the parietal cells requires challenging the cells with a sodium bicarbonate solution that will cause the stomach to become neutral or alkaline. The time it takes for the stomach to reacidify back down to its original fasting acid level will determine what condition the patient has. Reacidification time is vitally important in determining hypochlorhydria, hyperchlorhydria and achlorhydria. The second method of testing allows an untethered capsuled to migrate through the alimentary canal for testing the stomach, small and large bowel. This method requires a complete medical history in a controlled environment.
The mucus allows the acid at pH above 4 to penetrate lining, but below pH 4 (i.e. when acid is more concentrated) the acid cannot penetrate the mucus. This is called viscous fingering. Thus the foveolar cells can pump out a lot of acid, but acid once in the lumen of the stomach is prevented from returning.
In the small intestine, the pH becomes crucial; it needs to be finely balanced in order to activate digestive enzymes. The chyme is very acidic, with a low pH, having been released from the stomach and needs to be made much more alkaline. This is achieved in the duodenum by the addition of bile from the gall bladder combined with the bicarbonate secretions from the pancreatic duct and also from secretions of bicarbonate-rich mucus from duodenal glands known as Brunner's glands. The chyme arrives in the intestines having been released from the stomach through the opening of the pyloric sphincter. The resulting alkaline fluid mix neutralises the gastric acid which would damage the lining of the intestine. The mucus component lubricates the walls of the intestine.
"Escherichia coli", although considered to be part of the normal gut flora for many mammals (including humans), has many strains. Strain is associated with human illness (and sometimes death) as a foodborne illness. A study by Cornell University has determined that grass-fed animals have as much as eighty percent less of this strain of "E. coli" in their guts than their grain-fed counterparts, though this reduction can be achieved by switching an animal to grass only a few days prior to slaughter. Also, the amount of "E. coli" they do have is much less likely to survive our first-line defense against infection: stomach acid. This is because feeding grain to cattle makes their normally pH-neutral digestive tract abnormally acidic; over time, the pathogenic "E. coli" becomes acid resistant. If humans ingest this acid-resistant "E. coli" via grain-feed beef, a large number of them may survive past the stomach, causing an infection. A study by the USDA Meat and Animal Research Center in Lincoln Nebraska (2000) has confirmed the Cornell research.
A fecal pH test is one where a specimen of feces is tested for acidity in order to diagnose a medical condition. Human feces is normally acidic. An acidic stool can indicate a digestive problem such as lactose intolerance or a contagion such as "E. coli" or rotavirus, or overgrowth of the acid producing bacteria (such as lactic acid bacteria for instance).
The average pH for a healthy person is a pH of 6.6.
Hormones released during pregnancy softens the cardia muscle ring that keeps food within the stomach. Hydrochloric acid is the acid involved in gastric reflux, also known as morning sickness. This acid, at a pH of 1.5-3.5 coats the enamel on the teeth; at a pH of 6.5 and mainly affect the palatal surfaces of the maxillary teeth, eventually the enamel is softened and easily wears away.
Pepsin is most active in acidic environments between 37 °C and 42 °C. Accordingly, its primary site of synthesis and activity is in the stomach (pH 1.5 to 2). Pepsin will digest up to 20% of ingested amide bonds by cleaving preferentially at the C-terminal side of aromatic amino acids such as phenylalanine, tryptophan, and tyrosine. Pepsin exhibits preferential cleavage for hydrophobic, preferably aromatic, residues in P1 and P1' positions. Increased susceptibility to hydrolysis occurs if there is a sulfur-containing amino acid close to the peptide bond, which has an aromatic amino acid. Pepsin cleaves PheVal, GlnHis, GluAla, AlaLeu, LeuTyr, TyrLeu, GlyPhe, Phe in the insulin B chain. Pepsin exhibits maximal activity at pH 2.0 and is inactive at pH 6.5 and above, however pepsin is not fully denatured or irreversibly inactivated until pH 8.0. Therefore, pepsin in solution of up to pH 8.0 can be reactivated upon re-acidification. The stability of pepsin at high pH has significant implications on disease attributed to laryngopharyngeal reflux. Pepsin remains in the larynx following a gastric reflux event. At the mean pH of the laryngopharynx (pH = 6.8) pepsin would be inactive but could be reactivated upon subsequent acid reflux events resulting in damage to local tissues.