The patient with acute gastrointestinal problems
Peate Ian, Dutton Helen in Acute Nursing Care, 2020
The pancreas is a retroperitoneal gland approximately 12–15cm long and 2.5cm thick. It is connected by the pancreatic duct to the common bile duct, which in turn empties into the duodenum. Structurally, the pancreas is composed of clustered epithelial cells, about 99% of which constitute the exocrine portion of the organ. They secrete approximately 1200–1500mL daily of pancreatic juice, consisting of water, salts, sodium bicarbonate and enzymes. Bicarbonate pancreatic juice mixes with acidic chyme in the duodenum to neutralise the substance. Pancreatic juices consist of several enzymes that aid in the digestion of carbohydrates, proteins and fats. The protein digesting enzymes are secreted initially within the pancreas in an inactive form (trypsinogen), as the active form would damage the pancreas itself. Trypsinogen is only activated when it reaches the duodenum and mixes with other enzymes. It is the premature activation of trypsinogen, when it is still in the pancreas, which causes serious problems (pancreatitis). The remaining 1% of the cells are organised into pancreatic islets (islets of Langerhans), which have an endocrine function. These cells secrete hormones such as glucagon, insulin, somatostatin and pancreatic polypeptide (see section on diabetic emergencies in Chapter 11).
Hereditary Pancreatitis
Dongyou Liu in Handbook of Tumor Syndromes, 2020
The PRSS1 gene on chromosome 7q34 spans 12.8 kb and encodes a 247 aa, 26.5 kDa cationic trypsinogen (or trypsinogen-1, an inactive form of trypsin), which is a member of the trypsin family of serine proteases. Secreted by the pancreas, trypsinogen is cleaved of an eight-amino-acid trypsinogen activation peptide (TAP) by enterokinase to form active trypsin in the small intestine. TAP may be also cleaved by trypsin in the presence of calcium and association with a binding site formed in the activation region. The resultant active (mature) trypsin is an endopeptidase that cleaves peptide chains following a lysine or arginine, and converts inactive zymogens produced by the pancreas into active digestive enzymes in the duodenum upon food exposure. A second calcium-binding site in trypsinogen as well as trypsin may be occupied by calcium, which prevents trypsin degradation by trypsin on the autolysis site (Arg-122), and by chymotrypsin C (CTRC) at Leu-81 within the calcium binding site [9].
Gastroenterology
Stephan Strobel, Lewis Spitz, Stephen D. Marks in Great Ormond Street Handbook of Paediatrics, 2019
For reliable results, especially in the neonatal period, care has to be taken to collect at least 50 mg or, preferably, 100 mg of sweat. This may be difficult in very young infants. Serum trypsinogen: high level in early infancy. May be elevated in normal infants following abdominal surgery.Stool elastase: screening test for pancreatic insufficiency. Children with fecal elastase < 200µg/g should be treated with pancreatic exocrine replacement therapy (PERT).Pancreatic function tests: low volume of secretions with low bicarbonate but usually relatively normal enzyme levels. The test is now rarely used.Genetic markers include the ΔF508 gene mutation.Nasal potential difference, which can measure chloride and bicarbonate secretion in the nasal epithelium, is sometimes used as a confirmatory diagnostic test in reference centres.In older children chest CT might provide supportive evidence of CF with the finding of bronchiectasis (see also Chapter 4 Respiratory Medicine, page 80).
Inherited causes of exocrine pancreatic insufficiency in pediatric patients: clinical presentation and laboratory testing
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Tatiana N. Yuzyuk, Heather A. Nelson, Lisa M. Johnson
Pancreatic manifestations of EPI, such as abdominal pain, weight loss or poor weight gain, malnutrition, and steatorrhea, are not specific to CF and require a differential diagnosis to initiate appropriate treatment [16,17]. With the introduction of NBS, many infants affected with CF are identified within the first few weeks of life by measuring the levels of immunoreactive trypsinogen (IRT) in dried blood spots with subsequent variant analysis of the CFTR gene [4,18]. The sensitivity of this combined testing reaches more than 95% in Caucasians, although it is lower in nonwhite populations due to a limited number of race/ethnic-specific CFTR variants included on molecular NBS panels [18–20]. Multiple different combinations of IRT and DNA testing exist and each has varying cutoffs used to identify infants who require further testing. For IRT, some use fixed cutoffs, while others use floating cutoffs based on the 95th to 97th percentile (∼60 ng/ml) [18]. Detection of a CFTR pathogenic variant indicates a positive screen, but very high IRT (IRT value at 99.8–99.9 percentile) without positivity on DNA testing is also considered at risk. Positive screens are confirmed by sweat chloride testing, which remains one of the most accurate tests of CFTR function; chloride concentrations >60 mmol/L or <30 mmol/L are considered diagnostic or normal, respectively. Infants with intermediate concentrations between 30–59 mmol/L have an increased risk of CFTR-related disorders, such as the congenital bilateral absence of the vas deferens or recurrent pancreatitis, and they are closely monitored [4,21].
Recent advances in proteolytic stability for peptide, protein, and antibody drug discovery
Published in Expert Opinion on Drug Discovery, 2021
Xianyin Lai, Jason Tang, Mohamed E.H. ElSayed
The pancreas produces trypsinogen, an inactive precursor of trypsin. Trypsinogen is then secreted into the duodenum through the pancreatic duct. Once in the small intestine, the trypsinogen is activated by the enzyme enteropeptidase via proteolytic cleavage [54,55]. Trypsin is an endopeptidase and breaks peptide bonds down via a serine catalysis mechanism at an optimal pH of 7.5–8.5 [56]. The salmon calcitonin is a small peptide of 32 amino acids with a molecular weight of 3,432 Da and is a more potent analog of human calcitonin [57]. The salmon calcitonin was incubated with 0.5 μM trypsin in a sodium acetate (50 mM) buffer and it was completely degraded in 15 min [58]. The human granulocyte colony stimulating factor (G-CSF) is a major cytokine regulator of neutrophilic granulocytes and is able to stimulate the growth of neutrophil colonies from human bone marrow progenitor cells with a molecular weight of about 30,000 Da [59]. The incubation of 100 ug/ml of G-CSF with 1 ug/ml of trypsin revealed that G-CSF was susceptible to trypsin digestion and had about 30% intact protein at 4 h incubation [60].
Trypsinogen and chymotrypsinogen: potent anti-tumor agents
Published in Expert Opinion on Biological Therapy, 2021
Aitor González-Titos, Pablo Hernández-Camarero, Shivan Barungi, Juan Antonio Marchal, Julian Kenyon, Macarena Perán
The pancreas plays a very important role in the digestive function through the secretion of several enzymes necessary for the degradation of nutrients. These enzymes are secreted by acinar cells as zymogens (inactive forms also known as (pro)enzymes) [3]. Once secreted, they are transferred to the small intestine where they are activated. The most studied zymogens are Trypsinogen and Chymotrypsinogen. In the case of Trypsinogen, it is activated to Trypsin in the small intestine by enterokinase. Once activated, it is capable of activating the rest of the pancreatic zymogens, including Chymotrypsinogen into Chymotrypsin [4]. A failure in the production of these proteins can cause poor absorption of nutrients, the most common diseases that lead to exocrine pancreatic insufficiency are chronic pancreatitis and cystic fibrosis [5].
Related Knowledge Centers
- Amylase
- Chymotrypsinogen
- Digestive Enzyme
- Enteropeptidase
- Lipase
- Pancreas
- Pancreatic Juice
- Trypsin
- Zymogen
- Protein Precursor