Introduction
Shayne C. Gad in Toxicology of the Gastrointestinal Tract, 2018
Proton pumps powered by H/K ATPases actively transport H into the lumen while bringing potassium ions (K) into the cell (Figure 1.3). At the same time, Cl and K diffuse out through Cl and K channels in the apical membrane (next to the lumen). The enzyme carbonic anhydrase, which is especially plentiful in parietal cells, catalyzes the formation of carbonic acid (HCO) from water (HO) and carbon dioxide (CO). As carbonic acid dissociates, it provides a ready source of H for the proton pumps but also generates bicarbonate ions (HCOO). As HCO builds up in the cytosol, it exits the parietal cell in exchange for Clvia Cl/HCO antiporters in the basolateral membrane (next to the lamina propria). HCO diffuses into nearby blood capillaries. This “alkaline tide” of bicarbonate ions entering the bloodstream after a meal may be large enough to slightly elevate blood pH and make urine more alkaline. The strongly acidic fluid of the stomach kills many microbes in food, and HCL partially denatures proteins in food and stimulates the secretion of hormones that promote the flow of bile and pancreatic juice. Enzymatic digestion of proteins also begins in the stomach. The only proteolytic enzyme in the stomach is pepsin, which is secreted by chief cells. Because pepsin breaks certain peptide bonds between the amino acids making up proteins, a protein chain of many amino acids is broken down into smaller peptide fragments. Pepsin is most effective in the very acidic environment of the stomach (pH 2); it becomes inactive at higher pH. Note that pepsin is secreted in an inactive form called pepsinogen; in this form, it cannot digest the proteins in the chief cells that produce it. Pepsinogen is not converted into active pepsin until it comes in contact with active pepsin molecules or hydrochloric acid secreted by parietal cells. The stomach epithelial cells are also protected from gastric juices by a 1–3 mm thick layer of alkaline mucus secreted by surface mucous cells and mucous neck cells. Another enzyme of the stomach is gastric lipase, which splits the short-chain triglycerides in fat molecules found in milk into fatty acids and monoglycerides. This enzyme, which has a limited role in the adult stomach, operates best at a pH of 5–6. More important than either lingual lipase or gastric lipase is pancreatic lipase, an enzyme secreted by the pancreas into the small intestine. Only a small amount of absorption occurs in the stomach because its epithelial cells are impermeable to most materials. However, mucous cells of the stomach absorb some water, ions, and short-chain fatty acids, as well as certain drugs (especially aspirin and other “NSAIDs”) and alcohol.
Reflux Disease
John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford in Head & Neck Surgery Plastic Surgery, 2018
Pepsin is secreted in the form of pepsinogen, which is physiologically inactive. It is activated by cleavage in an acid environment (pH < 4). It had long been thought that pepsin was only active in a highly acidic environment (pH < 4), but recent research using human rather than porcine pepsin shows that, once activated, significant activity remains almost up to neutrality (pH = 7). Even at this level, the enzyme is not damaged, and can be reactivated by a fall in pH. It is not irreversibly deactivated until pH > 8. Pepsin binds to mucosa, and is even taken up into epithelial cells by endocytosis. If the pharynx or larynx is coated with refluxate after a reflux event, pepsin activity gradually decreases as the pH drifts toward neutrality, but can be quickly reactivated by another event, or by ingestion of an acidic bolus. Cola drinks, for instance, have a pH of < 2. As pepsin is active at higher pH levels than previously thought possible, investigation techniques that rely on a pH threshold of 4–4.5 may miss weakly acid or non-acid episodes that can cause tissue damage.
The Endocrine Pancreas
George H. Gass, Harold M. Kaplan in Handbook of Endocrinology, 2020
The pancreas is a retroperitoneal organ whose function is critical in the digestion of food and the metabolic regulation of fuels. The mature organ consists primarily of acinar exocrine tissue which produces digestive juices—predominantly bicarbonate and enzymes. The acinar production of bicarbonate and the release of its watery alkaline fluid through the pancreatic duct into the first portion of the duodenum is regulated through complex hormonal and physiochemical mechanisms. This bicarbonate-rich fluid neutralizes stomach acid to allow the action of pancreatic enzymes. Pancreatic amylase completes the digestion of ingested starches to disaccharides, a process begun in the mouth by salivary amylase; the absorption of monosaccharides through specific transporters occurs after action of disaccharidases on the microvilli of intestinal luminal cells. The breakdown of proteins to amino acids begins in the stomach with the action of pepsin. In a process akin to carbohydrate digestion, protein hydrolysis is mediated in large part by trypsin, chymotrypsin, and other endo- and ectopeptidases secreted from the pancreas, with intracellular and extracellular dipeptidases completing the process in the intestinal lining. Fat digestion begins in the intestine where bile salts allow for interaction of pancreatic lipase and co-lipase with dietary triglycerides resulting in their cleavage to fatty acids and monoglycerides, which are absorbed from the surface of intestinal cells by diffusion. Failure of the exocrine function of the pancreas is evidenced by weight loss, malnutrition, and diarrhea as a consequence of the malabsorption of nutrients; this generally occurs as a result of obstruction of the pancreatic ducts by stones or chronic inflammation. The focus of this chapter is on the endocrine actions of cells within the pancreas, which are contained within dispersed clusters termed islets of Langerhans. The islets comprise approximately 1–2% of the total pancreatic mass. These islets are complex mini-organs with specialized blood supply, autonomic innervation, and complex microcirculation. Of the endocrine cells within the islet, approximately 70–80% are the insulin-producing β cells, 5% somatostatin-producing δ cells, and 10–15% either glucagon-producing α cells or pancreatic-polypeptide producing PP cells. A variety of other hormone products are secreted in very small amounts from these and other rare cell types within islets. A critical problem for essentially all multicellular organisms is that basal energy needs are constant and increase in response to stress and activity while fuel intake is intermittent. The concerted action of the endocrine hormones of the pancreas produce the efficient deposition of carbohydrates, amino acids, and fats in the postabsorptive state and their regulated release from stores in the interdigestive period.
Effect of right lateral position with head elevation on tracheal aspirate pepsin in ventilated preterm neonates: randomized controlled trial
Published in The Journal of Maternal-Fetal & Neonatal Medicine, 2019
Safaa Shafik Imam, Dina Mohamed Shinkar, Nevine Ahmed Mohamed, Hebatallah Elhamy Mansour
Objective: To evaluate the effect of right lateral positioning in comparison with supine positioning on tracheal aspirate pepsin levels as a marker of aspiration of gastric contents in ventilated preterm neonates. Study design: This randomized controlled trial was conducted on 60 ventilated preterm neonates
Effect of pepsin on maintaining the supersaturation of the HCl salt of a weakly basic drug: a case study
Published in Pharmaceutical Development and Technology, 2016
Swathi Pinnamaneni, Frank A. Rinaldi, Dimuthu A. Jayawickrama, Jinjiang Li, Mandar V. Dali
The impact of pepsin on the maintenance of supersaturated solution of the HCl salt of a weakly basic drug was evaluated in simulated gastric fluid by monitoring the drug solubility in the absence and presence of pepsin. In the presence of pepsin, the HCl salt maintained its apparent solubility through 24 h, whereas, no such solubility advantage was seen in the absence of pepsin. Consequently, a minimum inhibitory concentration of pepsin is required for maintenance of supersaturation. In addition, NMR study seems to indicate a molecular level interaction between pepsin and HCl salt leading to a weak binding between the two. Therefore, for the HCl salts of weak bases having disproportionation potential, it is preferred that preformulation solubility studies are conducted in the presence of pepsin to reflect their in vivo behavior in maintaining supersaturation solubility.
Is the pepsin immunohistochemical staining of laryngeal lesions an available way for diagnosing laryngopharyngeal reflux
Published in Acta Oto-Laryngologica, 2020
Jiasen Wang, Jinrang Li, Xiaoyun Li, Shujun Zhang
Backgound: Pepsin immunohistochemical (IHC) staining is a promising diagnostic approach of laryngopharyngeal reflux (LPR). The interarytenoid mucosa has been proved to be an effective biopsy area. Objectives: To investigate whether positive result of pepsin IHC staining in laryngeal lesions can predict LPR. Methods: The study included 136 patients with laryngeal cancer or vocal cord leukoplakia. 24 h multichannel intraluminal impedance-pH (MII-pH) was performed before operation, and pepsin IHC staining was performed on pathological sections after operation. The results of the two methods were compared. Results: Among the 136 patients, 101 with at least one LPR event were regarded as MII-pH positive group, and another 35 were negative. The positive rate of pepsin IHC staining was 93.1% in MII-pH positive group and 54.1% in MII-pH negative group (p
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