Chronic Metabolic Acidosis Destroys Pancreas

  • Peter Melamed Biotherapy Clinic of San Francisco. San Francisco, CA, USA
  • Felix Melamed Biotherapy Clinic of San Francisco. San Francisco, CA, USA
Keywords: Acidosis, Digestive System, Pancreatic Juice, Pancreatitis

Abstract

One primary reason for the current epidemic of digestive disorders might be chronic metabolic acidosis, which is extremely common in the modern population. Chronic metabolic acidosis primarily affects two alkaline digestive glands, the liver, and the pancreas, which produce alkaline bile and pancreatic juice with a large amount of bicarbonate. Even small acidic alterations in the bile and pancreatic juice pH can lead to serious biochemical/biomechanical changes. The pancreatic digestive enzymes require an alkaline milieu for proper function, and lowering the pH disables their activity. It can be the primary cause of indigestion. Acidification of the pancreatic juice decreases its antimicrobial activity, which can lead to intestinal dysbiosis. Lowering the pH of the pancreatic juice can cause premature activation of the proteases inside the pancreas with the potential development of pancreatitis. The acidification of bile causes precipitation of the bile acids, which irritate the entire biliary system and create bile stone formation. Aggressive mixture of the acidic bile and the pancreatic juice can cause erratic contractions of the duodenum’s walls and subsequent bile reflux into the stomach and the esophagus. Normal exocrine pancreatic function is the core of proper digestion. Currently, there is no effective and safe treatment for enhancing the exocrine pancreatic function. Restoring normal acid-base homeostasis can be a useful tool for pathophysiological therapeutic approaches for various gastrointestinal disorders. There is strong research and practical evidence that restoring the HCO3- capacity in the blood can improve digestion.

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References

National Institutes of Health, U.S. Department of Health and Human Services. Opportunities and Challenges in Digestive Diseases Research: Recommendations of the National Commission on Digestive Diseases. Bethesda, MD: National Institutes of Health; 2009. NIH Publication 08–6514

Everhart JE, ed. The Burden of Digestive Diseases in the United States. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases. U.S. Dept of Health and Human Services; 2008. NIH Publication 09–6433

DeFrances CJ, Lucas CA, Buie VC, Golosinskiy A. 2006 National Hospital Discharge Survey. Natl Health Stat Report; 2008: 1-20. [PMID: 18841653]

Cherry DK, Hing E, Woodwell DA, Rechsteiner EA. National Ambulatory Medical Survey: 2006 Summary. Hyattsville, MD: National Center for Health Statistics; 2008: 1-39. [PMID: 18972720]

Camilleri M, Dubois D, Coulie B, et al. Prevalence and socioeconomic impact of upper gastrointestinal disorders in the United States: results of the US Upper Gastrointestinal Study. Clin Gastroenterol Hepatol 2005: 543-552. [PMID: 15952096]

Koeppen BM, Stanton BA. Renal Physiology. Mosby Physiology Monograph Series. 2013.

Melamed P, Melamed F. Healthy Pancreas, Healthy You. Part 1: Structure, Function, and Disorders of the Pancreas. Biotherapy Inc, San Francisco. https://www.smashwords.com/books/view/236176

Guyton AC. Human physiology and mechanism of disease. 1987: 499.

Scratcherd T, Case RM. The secretion of electrolytes by the pancreas. Am J Clinical Nutrition. 1973: 326-339 [PMID: 4266061]

Case RM, Scratcerd T, D’A Wynne R. The origin and secretion of pancreatic juice bicarbonate. J Physiol. (London) 1970: 1-15. [PMID: 5500780]

Ball EO, Tucker HF, Solomon AK, Vennesland B. The source of pancreatic juice bicarbonate. J. Biol Chem1941: 119.

Johnson LR, Byrne JH. Essential Medical Physiology. Academic Press, USA, 2003.

Matsuno S, Sasaki Y, Kobari M, et al. Initial Pathophysiological Changes in Chronic Pancreatitis Induced by Pancreatic Ductular Obstruction Model. Tohoku J Exp Med 1991: 199-210. [PMID: 1712129]

Lieb JG II, Draganov PV. Pancreatic function testing: Here to stay for the 21st century. World J Gastroenterol. 2008; 20: 3149–3158 [PMC: 2712845 ]

Talamini G. Duodenal Acidity May Increase the Risk of Pancreatic Cancer in the Course of Chronic Pancreatitis: An Etiopathogenetic Hypothesis. JOP. J Pancreas (Online) 2005; 6:122-127 [PMID: 15767727]

Saunders J H, Wormsley K G. Pancreatic extracts in the treatment of pancreatic exocrine insufficiency. Gut 1975; 16: 157-162. [PMID: 236213]

Introduction to Enzymes. Worthington Enzyme Manual. Worthington Biochemical Corporation. 2010. http://www.worthington-biochem.com/introbiochem/default.html

Mc Clave SA. Feeding the chronically ill patient. Audio-Digest Gastroenterology. 42nd Annual Gastroenterology Update. The Cleveland Clinic, Department of Gastroenterology and Hepatology. 2006.

Raeder M, Mo A, Aune S. Effect of plasma H+-ion concentration on pancreatic HCO-3 secretion. Acta Physiologica Scandinavica. 2008;105: 420-427 [PMID: 36734]

Nimmo J, Finlayson NDC, Smith AF, Shearman DJC. The production of calcium and magnesium during pancreatic function tests in health and disease. Gut. 1970; 11: 163–166. [PMID: 5441887]

Case RM, Harper AA, Scratcherd T. The secretion of electrolytes and enzymes by the pancreas of the anaesthetized cat. J. Physiol.1969;201:335-348 [PMID: 5780548]

Lee OY, Schmulson M, Mayer EA. Common functional gastrointestinal disorders: Nonulcer dyspepsia and irritable bowel syndrome. Clinical Cornerstone. 1999;1: 57-71 [PMID: 10682182]

Benda, J. Karlovarsky Mlynsky Pramen. Domaci pitna lecba. 1997.

Worning H. Exocrine Pancreatic Function in Dyspepsia. Digestion 1987; 37: 3-13. [PMID: 3497832]

Okada R, Okada A, Okada T, et al. Elevated Serum Lipase Levels in Patients with Dyspepsia of Unknown Cause in General Practice. Med Princ Pract. 2009; 18: 130-136. [PMID: 19204432].

Lindström E, Schenck H, Ihse I. Pancreatic exocrine and endocrine function in patients with pancreas divisum and abdominal pain. Int J Pancreatol. 1990; 6: 17-24. [PMID: 2230357].

Ashizawa N, Hashimoto T, Miyake T, et al. Efficacy of camostat mesilate compared with famotidine for treatment of functional dyspepsia: Is camostat mesilate effective? Journal of Gastroenterology and Hepatology. 2005;21(4):767-771 [PMID: 16677167].

Andren-Sandberg A, Hardt PD. Second Giessen International Workshop on Interactions of Exocrine and Endocrine Pancreatic Diseases. J Pancreas (Online) 2008; 9: 541-575. [PMID: 18648151]

Lott JA. Clinical Pathology of Pancreatic Disorders. Humana Press, Totowa, New Jersey. 1997.59.

Whitcomb DC. Advances in Understanding the Mechanisms Leading to Chronic Pancreatitis. Nat Clin Pract Gastroenterol Hepatol. 2004; 1: 46-52 [PMID: 16265044].

Green NM, Work E. Pancreatic Trypsin Inhibitor. 2. Reaction with trypsin. Biochem J. 1953; May;54(2):347–352 [PMID: 13058883].

Niederau C, Grendell JH. Intracellular vacuoles in experimental acute pancreatitis in rats and mice are an acidified compartment. J Clin Invest. 1988;81(1):229–236 [PMID: 3335639].

Bhoomagoud M, Jung T, Atladottir J, et al. Reducing extracellular pH sensitizes the acinar cell to secretagogue-induced pancreatitis responses in rats. Gastroenterology. 2009; 137: 1083–1092. [PMID: 19454288]

Hegyi P, Maleth J, Venglovecz V, Rakonczay Z. Pancreatic Ductal Bicarbonate Secretion: Challenge of the Acinar Acid Load. Front Physiol. 2011; 2: 36. [PMID: 21808623]

Matsuno S, Sasaki Y, Kobari M, et al. Initial Pathophysiological Changes in Chronic Pancreatitis Induced by Pancreatic Ductular Obstruction Model. Tohoku J Exp Med 1991; 163: 199-210. [PMID: 1712129]

Salo JA, Kivilaakso E. Contribution of trypsin and cholate to the pathogenesis of experimental alkaline reflux esophagitis. Scand J Gastroenterol 1984; 19: 875-881. [PMID: 6531656]

Cronin J, Williams L, McAdam E, et al. The role of secondary bile acids in neoplastic development in the oesophagus. Biochem Soc Trans 2010; 38: 337-342 [PMID: 20298179]

Roberto Penagini. Bile reflux and oesophagitis. European Journal of Gastroenterology & Hepatology: 2001; 13: 1-3 [PMID: 11204802].

Arendt T, Nizze H, Mönig H, Kloehn S, Stüber E, Fölsch UR. Biliary pancreatic reflux-induced acute pancreatitis-myth or possibility? Eur J Gastroenterol Hepatol. 1999; 11: 329-335 [PMID: 10333208]

Rege RV, Moore EW. Pathogenesis of calcium-containing gallstones. Canine ductular bile, but not gallbladder bile, is supersaturated with calcium carbonate. J Clin Invest. 1986; 77: 21–26 [PMID: 3944252]

Fitzpatrick W J, Zentler-Munro P L, Northfield T C. Ileal resection: effect of cimetidine and taurine on intrajejunal bile acid precipitation and lipid solubilisation. Gut. 1986; 27: 66–72. [PMID: 3949238]

Gregg JA. Detection of bacterial infection of the pancreatic ducts in patients with pancreatitis and pancreatic cancer during endoscopic cannulation of the pancreatic duct. Gastroenterology. 1977; 73: 1005-1007. [PMID: 332575]

Minelli EB, Benini A, Bassi C, Abbas H, Falconi M, Locatelli F, Marco R, Pederzolli P. Antimicrobial Activity of Human Pancreatic Juice and Its Interaction with Antibiotics. Antimicrob. Agents Chemother. 1996, 40: 2099. [PMID: 8878588].

Ramare F, Nicoli J, Dabard J, et al. Trypsin-dependent production of an antibacterial substance by a human Peptostreptococcus strain in gnotobiotic rats and in vitro. Appl Environ Microbiol.1993; 59: 2876–2883. [PMID: 8215361]

Rubinstein E, Mark Z, Haspel J, et al. Antibacterial activity of the pancreatic fluid. Gastroenterology. 1985 Apr; 88(4):927-32 [PMID: 3882511]

Pierzynowski SG, Zabielski R. Biology of the pancreas in growing animals. 1999; 131.

Agraharkar M. et al. Hypercalcemia. 2012. http://emedicine.medscape.com/article/240681- overview

Wiederkehr M, Krapf R Metabolic and endocrine effects of metabolic acidosis in humans. Swiss Med Wkly 2001; 131; 127-132 [PMID: 11416968]

Lesniak RJ, Hohenwalter MD, Taylor AJ. Spectrum of Causes of Pancreatic Calcifications. AJR January 2002; 178: 79-86. [PMID: 11756092]

Mateen MA1, Muheet KA, Mohan RJ, Rao PN, Majaz HM, et al. Evaluation of Ultrasound Based Acoustic Radiation Force Impulse (ARFI) and eSie touch Sonoelastography for Diagnosis of Inflammatory Pancreatic Diseases JOP. J Pancreas (Online) 2012; 13: 36-44. [PMID: 22233945]

Hofmann AF, Mysels KJ. Bile acid solubility and precipitation in vitro and in vivo: the role of conjugation, pH, and Ca2+ ions. Journal of Lipid Research. 1992; 33:617-626 [PMID: 1619357]

Frassetto L, Morris RC, Sebastian A. Potassium Bicarbonate Reduces Urinary Nitrogen Excretion in Postmenopausal Women. Journal of Clinical Endocrinology and Metabolism 1997; 82: 254-259 [PMID: 8989270]

Frassetto L, Sebastian A. Age and systemic acid-base equilibrium: analysis of published data. J Gerontol. 1996; 51:91-99. [PMID: 8548506].

Frassetto L, Morris Jr RC, Sebastian A. Effect of age on blood acid-base composition in adult humans: role of age-related renal functional decline. Am J Physiol. 1996; 271: 1114–1122 [PMID: 8997384]

Eaton SB, Konner MJ, Cordain L. Diet-dependent acid load, Paleolithic nutrition, and evolutionary health promotion. Am J Clin Nutr 2010; 91: 295–297. [PMID: 20042522]

Ströhle A, Hahn A, Sebastian A. Estimation of the diet-dependent net acid load in 229 worldwide historically studied hunter-gatherer societies. Am J Clin Nutr 91: 406-412. 2010. [PMID: 20042527]

Alpern RJ, Sakhaee K. The clinical spectrum of chronic metabolic acidosis: homeostatic mechanisms produce significant morbidity. Am J Kidney Dis. 1997; 29: 291-302. [PMID: 9016905]

Sebastian A, Frassetto LA, Sellmeyer DE, Merriam RL, Morris RC. Estimation of the net acid load of the diet of ancestral preagricultural Homo sapiens and their hominid ancestors. Am J Clin Nutr 2002; 76: 1308-1316. [PMID: 12450898]

Vormann J, Remer T. Dietary, Metabolic, Physiologic, and Disease-Related Aspects of Acid-Base Balance: Foreword to the Contributions of the Second International Acid-Base Symposium. J. Nutr 2008; 138: 413-414. [PMID: 18203912]

Gullo L. Alcohol and Chronic Pancreatitis: Leading or Secondary Etiopathogenetic Role? JOP. J Pancreas (Online) 2005; 6: 68-72. [PMID: 15650289]

Irving HM, Samokhvalov AV, Rehm J. Alcohol as a Risk Factor for Pancreatitis. A Systematic Review and Meta-Analysis. JOP. J Pancreas (Online) 2009; 10: 387-392. [PMID: 19581740].

Criddle DN1, Raraty MG, Neoptolemos JP, Tepikin AV, Petersen OH, et al. Ethanol toxicity in pancreatic acinar cells: Mediation by nonoxidative fatty acid metabolites. Proc Natl Acad Sci USA. 2004; 101: 10738–10743.[PMID: 15247419]

Irving HM, Samokhvalov AV, Rehm J. Alcohol as a Risk Factor for Pancreatitis. A Systematic Review and Meta-Analysis. JOP. J Pancreas (Online) 2009; 10: 387-392. [PMID: 19581740]

Judge BS. Metabolic Acidosis: Differentiating the Causes in the Poisoned Patient. Med Clin N Am 2005; 89: 1107–1124 [PMID: 16227056]

Gunnerson KJ, Pinsky MR. Lactic Acidosis. http://emedicine.medscape.com/article/167027-overview.

Hisato Igarashi at al Acetaminophen-Induced Acute Pancreatitis. A Case Report. JOP. J Pancreas (Online) 2009; 10: 550-553. [PMID: 19734636]

Solc, P. Karlovarska lazenska leba a medicina na prelomu 20. A21. Stoleti. 2000.

Frulloni L, Patrizi F, Bernardoni L, Cavallini G. Pancreatic Hyperenzymemia: Clinical Significance and Diagnostic Approach. JOP. J Pancreas (Online) 2005; 6: 536-551. [PMID: 16286704]

Liamis G et al. Pharmacologically-Induced Metabolic Acidosis. Drug Saf. 2010; 33: 371-391. [PMID: 20397738]

Burckhardt P. The effect of the alkali load of mineral water on bone metabolism: interventional studies. J Nutr 2008 Feb;138(2):435S-437S [PMID: 18203918]

McCance K, Huether S. Pathophysiology: the biologic basis for diseases in adults and children. 2nd ed. 1994, Mosby.

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Published
2014-11-28
How to Cite
Melamed, P., & Melamed, F. (2014). Chronic Metabolic Acidosis Destroys Pancreas. JOP. Journal of the Pancreas, 15(6), 552-560. https://doi.org/10.6092/1590-8577/2854