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Normal Liver Function: A Basis for Understanding Hepatic Disease

Normal Liver Function: A Basis for Understanding Hepatic Disease Abstract • The physiology of the liver involves metabolism, excretion, and body defense. Within the context of metabolism, the liver is the site of a multitude of biochemical reactions essential to the human organism; included are synthesis, degradation, interconversion, storage, and biotransformation. A working knowledge of the relationship between structure and function and of hepatic processes under normal conditions is essential for understanding the derangements observed in clinical diseases affecting the liver. Our overview of hepatic physiology highlights some of these facets of normal hepatic anatomy and function of special relevance to the physician confronting liver dysfunction and its varied clinical consequences. (Arch Intern Med 1983;143:2291-2294) References 1. Kiernan F: The anatomy and physiology of the liver. Philos Trans R Soc Lond Biol 1833;123:711-770.Crossref 2. Rappaport AM, Borowy ZJ, Lougheed WM, et al: Subdivision of hexagonal liver lobules into a structural and functional unit: Role in hepatic physiology and pathology. Anat Rec 1954;119:11-27.Crossref 3. Jungermann K, Katz N: Functional hepatocellular heterogeneity. Hepatology 1982;2:385-395.Crossref 4. Gumucio JJ, Miller DL: Functional implications of liver cell heterogeneity. Gastroenterology 1981;80:393-403. 5. Rappaport AM, Hiraki GY: The anatomical pattern of lesions in the liver. Acta Anat 1958;32:126-140.Crossref 6. Brauer RW: Liver circulation and function. Physiol Rev 1963;43: 115-213. 7. Rothschild MA, Oratz M, Schreiber SS: Albumin synthesis. N Engl J Med 1972;286:748-757,816-821.Crossref 8. Werner M: Serum protein changes during the acute phase reaction. Clin Chim Acta 1969;25:299-305.Crossref 9. Cascino A, Cangiano C, Calcaterra V, et al: Plasma amino acids imbalance in patients with liver disease. Dig Dis 1978;23:591-598.Crossref 10. Saudek CK, Felig P: The metabolic events of starvation. Am J Med 1976;60:117-126.Crossref 11. Cahil GF Jr: Starvation in man. N Engl J Med 1970;282:668-675.Crossref 12. Krebs HA, Freedland RA, Hems R, et al: Inhibition of hepatic gluconeogeneses by ethanol. Biochem J 1969;112:117-124. 13. Tall AR, Small DM: Plasma high-density lipoproteins. N Engl J Med 1978;299:1232-1236.Crossref 14. Rhoads GG, Gulbrandsen CL, Kagan A: Serum lipoproteins and coronary heart disease in a population study of Hawaiian Japanese men. N Engl J Med 1976;294:293-298.Crossref 15. Jackson RL, Morrisett JD, Gotto AM Jr: Lipoprotein structure and metabolism. Physiol Rev 1976;56:259-316. 16. Olson JA: The biosynthesis of cholesterol. Ergeb Physiol 1965;56: 173-215.Crossref 17. Bhattathiry EPM, Siperstein MD: Feedback control of cholesterol synthesis in man. J Clin Invest 1963;42:1613-1618.Crossref 18. Siperstein MD, Fagan VM: Deletion of the cholesterol—negative feedback system in liver tumors. Cancer Res 1964;24:1108-1115. 19. Zimmerman HJ: Hepatic metabolism of foreign compounds , in Hepatoxicity . New York, Appleton-Century-Crofts, 1978, pp 11-31. 20. Schmucker DL: Age-related changes in drug disposition. Pharmacol Rev 1979;30:445-456. 21. Klotz U, Avant GR, Hoyumpa A, et al: The effect of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest 1975;55:347-359.Crossref 22. Roberts RK, Wilkinson GR, Branch RA, et al: Effect of age and parenchymal liver disease on the disposition and elimination of chlordiazepoxide (Librium). Gastroenterology 1978;75:479-485. 23. Klotz U, Reimann I: Delayed clearance of diazepam due to cimetidine. N Engl J Med 1980;302:1012-1014.Crossref 24. Shull HJ, Wilkinson GR, Johnson R, et al: Normal disposition of oxazepam in acute viral hepatitis and cirrhosis. Ann Intern Med 1976;84: 420-425.Crossref 25. Kraus JW, Desmond PV, Marshall JP, et al: Effect of aging and liver disease on disposition of lorazepam. Clin Pharm Ther 1978;24:411-419. 26. Shand DG, Rangno RE: The disposition of propranolol: I. Elimination during oral absorption in man. Pharmacology 1972;7:159-168.Crossref 27. Crigler JF, Najjar VA: Congenital familial non-hemolytic jaundice with kernicterus. Pediatrics 1952;10:169-180. 28. Judah JD, McLean AEM, McLean EK: Biochemical mechanisms of liver injury. Am J Med 1970;49:609-616.Crossref 29. Mitchell JR, Nelson SD, Thorgeirsson SS, et al: Metabolic activation: Biochemical basis for many drug-induced liver injuries , in Popper H, Schaffner F (eds): Progress in Liver Diseases . New York, Grune & Stratton Inc, 1976, vol 5, pp 259-279. 30. Mitchell JR, Jollows DJ: Metabolic activation of drugs to toxic substances. Gastroenterology 1975;68:392-410. 31. Mitchell JR, Zimmerman HJ, Ishak KG, et al: Isoniazid liver injury: Clinical spectrum, pathology and probable pathogenesis. Ann Intern Med 1976;84:181-192.Crossref 32. Mitchell JR, Thorgeirsson SS, Potter WZ, et al: Acetaminophen-induced hepatic injury: Protective role of glutathione in man and rationale for therapy. Clin Pharmacol Ther 1974;16:676-684. 33. Wheeler HO: Water and electrolytes in bile , in Code CF (ed): Handbook of PHysiology . Washington, DC, American Physiological Society, 1968, section 6, pp 2409-2431. 34. Moore RB, Anderson JT, Taylor HL, et al: Effect of dietary fat on the fecal excretion of cholesterol and its degradation products in man. J Clin Invest 1968;47:1517-1534.Crossref 35. Tyor MP, Garbutt JT, Lack L: Metabolism and transport of bile salts in the intestine. Am J Med 1971;51:614-626.Crossref 36. Borgstrom B, Lundh G, Hofmann A: The site of absorption of conjugated bile salts in man. Gastroenterology 1963;45:229-238. 37. Lack L, Weiner IM: Intestinal bile salt transport: Structure activity relationships and other properties. Am J Physiol 1966;210:1142-1152. 38. Borgstrom B, Dahlqvist A, Lundh G, et al: Studies of intestinal digestion and absorption in the human. J Clin Invest 1957;36:1521-1536.Crossref 39. Heaton KW, Read AE: Gallstones in patients with disorders of the terminal ileum and disturbed bile salt metabolism. Br Med J 1969;3:494-496.Crossref 40. Lester R, Schmid R: Bilirubin metabolism. N Engl J Med 1964;270: 779-786.Crossref 41. Lester R, Schmid R: Intestinal absorption of bile pigments: I. The enterohepatic circulation of bilirubin in the rat. J Clin Invest 1963;42:736-746.Crossref 42. Biozzi G, Stiffel C: The pathophysiology of the reticuloendothelial cells of the liver and spleen , in Popper H, Schaffner F (eds): Progress in Liver Diseases . New York, Grune & Stratton Inc, 1965, vol 2, pp 166-191. 43. Nolan JP: Endotoxin, reticuloendothelial function and liver injury. Hepatology 1981;1:458-465.Crossref 44. Taro K, So K, Moroi T, et al: Detection of endotoxin in plasma and ascites of patients with cirrhosis: Its clinical significance. Gastroenterology 1976;73:539-542. 45. Nagura H, Smith PD, Nakane PK, et al: IgA in human bile and liver. J Immunol 1981;126:587-595. 46. Kutteh WH, Prince SJ, Phillips JO, et al: Properties of immunoglobulin A in serum of individuals with liver diseases and in hepatic bile. Gastroenterology 1982;82:184-193. 47. Kleinman RE, Harmatz PR, Walker WA: The liver: An integral part of the enteric mucosal immune system. Hepatology 1982;2:379-384.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Normal Liver Function: A Basis for Understanding Hepatic Disease

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Publisher
American Medical Association
Copyright
Copyright © 1983 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1983.00350120085018
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Abstract

Abstract • The physiology of the liver involves metabolism, excretion, and body defense. Within the context of metabolism, the liver is the site of a multitude of biochemical reactions essential to the human organism; included are synthesis, degradation, interconversion, storage, and biotransformation. A working knowledge of the relationship between structure and function and of hepatic processes under normal conditions is essential for understanding the derangements observed in clinical diseases affecting the liver. Our overview of hepatic physiology highlights some of these facets of normal hepatic anatomy and function of special relevance to the physician confronting liver dysfunction and its varied clinical consequences. (Arch Intern Med 1983;143:2291-2294) References 1. Kiernan F: The anatomy and physiology of the liver. Philos Trans R Soc Lond Biol 1833;123:711-770.Crossref 2. Rappaport AM, Borowy ZJ, Lougheed WM, et al: Subdivision of hexagonal liver lobules into a structural and functional unit: Role in hepatic physiology and pathology. Anat Rec 1954;119:11-27.Crossref 3. Jungermann K, Katz N: Functional hepatocellular heterogeneity. Hepatology 1982;2:385-395.Crossref 4. Gumucio JJ, Miller DL: Functional implications of liver cell heterogeneity. Gastroenterology 1981;80:393-403. 5. Rappaport AM, Hiraki GY: The anatomical pattern of lesions in the liver. Acta Anat 1958;32:126-140.Crossref 6. Brauer RW: Liver circulation and function. Physiol Rev 1963;43: 115-213. 7. Rothschild MA, Oratz M, Schreiber SS: Albumin synthesis. N Engl J Med 1972;286:748-757,816-821.Crossref 8. Werner M: Serum protein changes during the acute phase reaction. Clin Chim Acta 1969;25:299-305.Crossref 9. Cascino A, Cangiano C, Calcaterra V, et al: Plasma amino acids imbalance in patients with liver disease. Dig Dis 1978;23:591-598.Crossref 10. Saudek CK, Felig P: The metabolic events of starvation. Am J Med 1976;60:117-126.Crossref 11. Cahil GF Jr: Starvation in man. N Engl J Med 1970;282:668-675.Crossref 12. Krebs HA, Freedland RA, Hems R, et al: Inhibition of hepatic gluconeogeneses by ethanol. Biochem J 1969;112:117-124. 13. Tall AR, Small DM: Plasma high-density lipoproteins. N Engl J Med 1978;299:1232-1236.Crossref 14. Rhoads GG, Gulbrandsen CL, Kagan A: Serum lipoproteins and coronary heart disease in a population study of Hawaiian Japanese men. N Engl J Med 1976;294:293-298.Crossref 15. Jackson RL, Morrisett JD, Gotto AM Jr: Lipoprotein structure and metabolism. Physiol Rev 1976;56:259-316. 16. Olson JA: The biosynthesis of cholesterol. Ergeb Physiol 1965;56: 173-215.Crossref 17. Bhattathiry EPM, Siperstein MD: Feedback control of cholesterol synthesis in man. J Clin Invest 1963;42:1613-1618.Crossref 18. Siperstein MD, Fagan VM: Deletion of the cholesterol—negative feedback system in liver tumors. Cancer Res 1964;24:1108-1115. 19. Zimmerman HJ: Hepatic metabolism of foreign compounds , in Hepatoxicity . New York, Appleton-Century-Crofts, 1978, pp 11-31. 20. Schmucker DL: Age-related changes in drug disposition. Pharmacol Rev 1979;30:445-456. 21. Klotz U, Avant GR, Hoyumpa A, et al: The effect of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest 1975;55:347-359.Crossref 22. Roberts RK, Wilkinson GR, Branch RA, et al: Effect of age and parenchymal liver disease on the disposition and elimination of chlordiazepoxide (Librium). Gastroenterology 1978;75:479-485. 23. Klotz U, Reimann I: Delayed clearance of diazepam due to cimetidine. N Engl J Med 1980;302:1012-1014.Crossref 24. Shull HJ, Wilkinson GR, Johnson R, et al: Normal disposition of oxazepam in acute viral hepatitis and cirrhosis. Ann Intern Med 1976;84: 420-425.Crossref 25. Kraus JW, Desmond PV, Marshall JP, et al: Effect of aging and liver disease on disposition of lorazepam. Clin Pharm Ther 1978;24:411-419. 26. Shand DG, Rangno RE: The disposition of propranolol: I. Elimination during oral absorption in man. Pharmacology 1972;7:159-168.Crossref 27. Crigler JF, Najjar VA: Congenital familial non-hemolytic jaundice with kernicterus. Pediatrics 1952;10:169-180. 28. Judah JD, McLean AEM, McLean EK: Biochemical mechanisms of liver injury. Am J Med 1970;49:609-616.Crossref 29. Mitchell JR, Nelson SD, Thorgeirsson SS, et al: Metabolic activation: Biochemical basis for many drug-induced liver injuries , in Popper H, Schaffner F (eds): Progress in Liver Diseases . New York, Grune & Stratton Inc, 1976, vol 5, pp 259-279. 30. Mitchell JR, Jollows DJ: Metabolic activation of drugs to toxic substances. Gastroenterology 1975;68:392-410. 31. Mitchell JR, Zimmerman HJ, Ishak KG, et al: Isoniazid liver injury: Clinical spectrum, pathology and probable pathogenesis. Ann Intern Med 1976;84:181-192.Crossref 32. Mitchell JR, Thorgeirsson SS, Potter WZ, et al: Acetaminophen-induced hepatic injury: Protective role of glutathione in man and rationale for therapy. Clin Pharmacol Ther 1974;16:676-684. 33. Wheeler HO: Water and electrolytes in bile , in Code CF (ed): Handbook of PHysiology . Washington, DC, American Physiological Society, 1968, section 6, pp 2409-2431. 34. Moore RB, Anderson JT, Taylor HL, et al: Effect of dietary fat on the fecal excretion of cholesterol and its degradation products in man. J Clin Invest 1968;47:1517-1534.Crossref 35. Tyor MP, Garbutt JT, Lack L: Metabolism and transport of bile salts in the intestine. Am J Med 1971;51:614-626.Crossref 36. Borgstrom B, Lundh G, Hofmann A: The site of absorption of conjugated bile salts in man. Gastroenterology 1963;45:229-238. 37. Lack L, Weiner IM: Intestinal bile salt transport: Structure activity relationships and other properties. Am J Physiol 1966;210:1142-1152. 38. Borgstrom B, Dahlqvist A, Lundh G, et al: Studies of intestinal digestion and absorption in the human. J Clin Invest 1957;36:1521-1536.Crossref 39. Heaton KW, Read AE: Gallstones in patients with disorders of the terminal ileum and disturbed bile salt metabolism. Br Med J 1969;3:494-496.Crossref 40. Lester R, Schmid R: Bilirubin metabolism. N Engl J Med 1964;270: 779-786.Crossref 41. Lester R, Schmid R: Intestinal absorption of bile pigments: I. The enterohepatic circulation of bilirubin in the rat. J Clin Invest 1963;42:736-746.Crossref 42. Biozzi G, Stiffel C: The pathophysiology of the reticuloendothelial cells of the liver and spleen , in Popper H, Schaffner F (eds): Progress in Liver Diseases . New York, Grune & Stratton Inc, 1965, vol 2, pp 166-191. 43. Nolan JP: Endotoxin, reticuloendothelial function and liver injury. Hepatology 1981;1:458-465.Crossref 44. Taro K, So K, Moroi T, et al: Detection of endotoxin in plasma and ascites of patients with cirrhosis: Its clinical significance. Gastroenterology 1976;73:539-542. 45. Nagura H, Smith PD, Nakane PK, et al: IgA in human bile and liver. J Immunol 1981;126:587-595. 46. Kutteh WH, Prince SJ, Phillips JO, et al: Properties of immunoglobulin A in serum of individuals with liver diseases and in hepatic bile. Gastroenterology 1982;82:184-193. 47. Kleinman RE, Harmatz PR, Walker WA: The liver: An integral part of the enteric mucosal immune system. Hepatology 1982;2:379-384.Crossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Dec 1, 1983

References