Karaciğerin Hücresel Yapısı ve Fonksiyonel Dinamikleri

Abstract

Karaciğer, olağanüstü yeteneklere ve çok çeşitli işlevlere sahip eşsiz bir organdır. Karaciğer, metabolizmada, detoksifikasyonda ve çok sayıda fizyolojik sürecin düzenlenmesinde hayati roller oynar. Sindirim sistemi, kardiyovasküler sistem, endokrin bezleri, böbrekler ve bağışıklık sistemi dâhil olmak üzere çeşitli organlar ve sistemlerle yakın etkileşime girerek homeostazı korur. Bu etkileşimler besin metabolizması, hormon düzenlemesi ve vücudun savunma mekanizmaları için gereklidir. Karaciğer aynı zamanda enerji dengesinin korunmasında önemli bir merkezdir; açlık ve tokluk durumlarına göre glikojen depolama, glukoneogenez ve lipogenez gibi süreçleri düzenler. Ek olarak, vücut ısısının korunmasına katkıda bulunur ve yaşlanmayla birlikte yapısal ve işlevsel değişiklikler gösteren dinamik bir organdır. Yapısal olarak karaciğer, metabolik süreçlerin ana yürütücüsü olan hepatositler, immün savunmadan sorumlu Kupffer hücreleri, vitamin A depolayan ve doku onarımında rol oynayan hepatik yıldız hücreleri ile seçici madde alışverişini düzenleyen karaciğer sinüzoidal endotel hücrelerinden oluşur. Bu hücre gruplarının her biri, karaciğerin safra üretimi ve salgılanması, bilirubin metabolizması, besinlerin işlenmesi, toksinlerin detoksifikasyonu, mineral ve vitamin depolanması, bağışıklık tepkilerinin düzenlenmesi, ayrıca vasküler ve hematolojik süreçlerin sürdürülmesi gibi çeşitli fizyolojik işlevlerini yerine getirmesine katkıda bulunur. Bu derlemede metabolizmanın merkezi olan karaciğerin hücresel bileşenleri ve işlevsel yönleri incelenmiş, karaciğerin metabolik bir güç merkezi ve sistemik homeostazın çok yönlü ve dinamik bir düzenleyicisi olarak üstlendiği roller ele alınmıştır.

Keywords

• Fizyoloji
• Fonksiyon
• Hepatosit
• Karaciğer
• Metabolizma

Cellular Structure and Functional Dynamics of the Liver

Abstract

The liver is a unique organ with extraordinary capabilities and a wide range of functions. It plays vital roles in metabolism, detoxification, and the regulation of numerous physiological processes. It maintains homeostasis by closely interacting with various organs and systems, including the digestive system, cardiovascular system, endocrine glands, kidneys, and immune system. These interactions are essential for nutrient metabolism, hormone regulation, and the body's defense mechanisms. The liver is also an important center for maintaining energy balance; it regulates processes such as glycogen storage, gluconeogenesis, and lipogenesis according to fasting and fed states. Additionally, it contributes to the maintenance of body temperature and is a dynamic organ that undergoes structural and functional changes with aging. Structurally, the liver consists of hepatocytes, which are the main executors of metabolic processes; Kupffer cells, responsible for immune defense; hepatic stellate cells, which store vitamin A and play a role in tissue repair; and hepatic sinusoidal endothelial cells, which regulate the selective exchange of substances. Each of these cell groups contributes to the liver's various physiological functions, such as bile production and secretion, bilirubin metabolism, nutrient processing, detoxification of toxins, storage of minerals and vitamins, regulation of immune responses, and maintenance of vascular and hematological processes. This review examines the cellular components and functional aspects of the liver, the central organ of metabolism, and addresses its roles as a metabolic powerhouse and a versatile, dynamic regulator of systemic homeostasis.

Keywords

• Physiology
• Function
• Hepatocyte
• Liver
• Metabolism

References

1. 1. Ugo L, Brocco S, Merola A, et al. Liver anatomy. Imaging of the Liver and Intra-hepatic Biliary Tract: Volume 1: Imaging Techniques and Non-tumoral Pathologies, Quaia E (Ed). Springer, Cham, 2021; s. 15-47. doi:10.1007/978-3-030-38983-3_2.
2. 2. Ou Q, Mu H, Zhou C, et al. Liver diseases. Clinical Molecular Diagnostics, Pan S, Tang J (Eds). Springer, Cham, 2021; s. 463-492. doi:10.1007/978-981-16-1037-0_33.
3. 3. Muriel P. Some experimental models of liver damage. Hepatotoxicity: From Genomics to in Vitro and in Vivo Models, Sahu SC (Ed). Wiley, Hoboken (NJ), 2007; s. 119-137. doi:10.1002/9780470516751.
4. 4. Tortora GJ, Derrickson BH. Principles of Anatomy and Physiology. 12th ed. John Wiley & Sons, Hoboken (NJ), 2008.
5. 5. Singh I. Textbook of Anatomy with Colour Atlas. Vol 2. 4th ed. Jaypee Brothers, New Delhi, 2008. ISBN: 9788180618314.
6. 6. Zhang S, Chen W, Zhu C. Liver structure. Artificial Liver, Li L (Ed), Cham. Springer, 2021; s. 21-47. doi:10.1007/978-981-15-5984-6_2.
7. 7. Muriel P. Liver Pathophysiology: Therapies and Antioxidants. Academic Press, London, 2017. ISBN: 9780128043219.
8. 8. Allen SE. The Liver: Anatomy, Physiology, Disease, and Treatment. North Eastern University Press, Boston (MA), 2002.

9. 9. Michalopoulos GK, Bhushan B. Liver regeneration: Biological and pathological mechanisms and implications. Nat Rev Gastroenterol Hepatol. 2021;18(1):40-55. doi:10.1038/s41575-020-0342-4.
10. 10. Tabibian JH, LaRusso NF. Liver and bile. Reference Module in Biomedical Sciences, 5th ed. Amsterdam. Elsevier, 2014; s. 337-343. doi:10.1016/B978-0-12-801238-3.00047-7.
11. 11. Miyamura N, Nishina H. Molecular mechanisms of liver development: Lessons from animal models. Stem Cells and Cancer in Hepatology, Zheng YW (Ed). Academic Press, London, 2018; s. 1-20. doi:10.1016/B978-0-12-812301-0.00001-3.
12. 12. Allison DB, Borzik D, Li QK. Liver cytology. Atlas of Non-Gynecologic Cytology, Jing X, Siddiqui MT, Li QK (Eds). Springer, Cham, 2018; s. 173-198. doi:10.1007/978-3-319-89674-8_7.
13. 13. Schulze RJ, Schott MB, Casey CA, et al. The cell biology of the hepatocyte: A membrane trafficking machine. J Cell Biol. 2019; 218(7):2096-2112. doi:10.1083/jcb.201903090.
14. 14. Dutta S, Mishra SP, Sahu AK, et al. Hepatocytes and their role in metabolism. Drug Metabolism, Dunnington K (Ed). IntechOpen, London, 2021; s. 3-18. ISBN: 9781839688805.
15. 15. Ozougwu JC. Physiology of the liver. Int J Res Pharm Biosci. 2017; 4(8):13-24.
16. 16. Butura A. Drug and alcohol induced hepatotoxicity [dissertation]. Karolinska Institutet, Department of Physiology and Pharmacology, Stockholm, Sweden; 2008.
17. 17. Nagaty BA. Evaluation of the potential protective effect of cinnamon extract against carbon tetrachloride-induced oxidative stress and hepatotoxicity in male albino rats [dissertation]. King Abdulaziz University, Jeddah, Saudi Arabia; 2019.
18. 18. Shetty S, Lalor PF, Adams DH. Liver sinusoidal endothelial cells—Gatekeepers of hepatic immunity. Nat Rev Gastroenterol Hepatol. 2018; 15(9):555-567. doi:10.1038/s41575-018-0020-y.
19. 19. Poisson J, Lemoinne S, Boulanger C, et al. Liver sinusoidal endothelial cells: Physiology and role in liver diseases. J Hepatol. 2017; 66(1):212-227. doi:10.1016/j.jhep.2016.07.009.
20. 20. Bhandari S, Larsen AK, McCourt P, Smedsrød B, Sørensen KK. The scavenger function of liver sinusoidal endothelial cells in health and disease. Front Physiol. 2021; 12:757469. doi:10.3389/fphys.2021.757469.
21. 21. Stolz DB. Sinusoidal endothelial cells. Molecular Pathology of Liver Diseases, Monga SPS (Ed). Springer, New York, 2011; s. 97-107. doi:10.1007/978-1-4419-7107-4_7.
22. 22. Koyama Y, Xu J, Liu X, et al. New developments on the treatment of liver fibrosis. Dig Dis. 2016; 34:589-596. doi:10.1159/000445269.
23. 23. Senoo H, Mezaki Y, Fujiwara M. The stellate cell system (vitamin A-storing cell system). Anat Sci Int. 2017; 92:387-455. doi:10.1007/s12565-017-0395-9.
24. 24. Huang Y, Deng X, Liang J. Modulation of hepatic stellate cells and reversibility of hepatic fibrosis. Exp Cell Res. 2017; 352:420-426. doi:10.1016/j.yexcr.2017.02.038.
25. 25. Liu X, Wang H, Liang X, et al. Hepatic metabolism in liver health and disease. Liver Pathophysiology, Muriel P (Ed). Academic Press, London, 2017; s. 391-400. doi:10.1016/B978-0-12-804274-8.00030-8.
26. 26. Luo N, Li J, Wei Y, et al. Hepatic stellate cell: a double-edged sword in the liver. Physiol Res. 2021; 70(6):821. doi:10.33549/physiolres.934755.
27. 27. Elchaninov AV, Fatkhudinov TK, Vishnyakova PA, et al. Phenotypical and functional polymorphism of liver resident macrophages. Cells. 2019; 8(9):1032. doi:10.3390/cells8091032.
28. 28. Nguyen-Lefebvre AT, & Horuzsko A. Kupffer cell metabolism and function. J Enzymol Metab. 2015; 1(1): 101.
29. 29. Dixon LJ, Barnes M, Tang H, et al. Kupffer cells in the liver. Compr Physiol. 2013; 3(2):785. doi:10.1002/cphy.c120026.
30. 30. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol. 2005; 5: 953-964. https://doi.org/10.1038/nri1733
31. 31. Tateya S, Rizzo NO, Handa P, et al. Endothelial NO/cGMP/VASP signaling attenuates Kupffer cell activation and hepatic insulin resistance induced by high-fat feeding. Diabetes. 2011; 60: 2792-2801. https://doi.org/10.2337/db11-0255
32. 32. Tsukamoto H. Redox regulation of cytokine expression in Kupffer cells. Antioxid Redox Signal. 2002; 4(5): 741-748. https://doi.org/10.1089/15230860276059888
33. 33. Boyer JL. Bile formation and secretion. Compr Physiol. 2013; 3(3):1035-1078. doi:10.1002/cphy.c120027.
34. 34. Frisch K, Hofmann AF. Biliary secretion. Functional Molecular Imaging in Hepatology, Keiding S, Sørensen M (Eds). Bentham Science Publishers, Sharjah, 2012; s. 49-75. doi:10.2174/97816080529051120101.
35. 35. Hall JE, Hall ME. Guyton and Hall Textbook of Medical Physiology. 14th ed. Elsevier, Philadelphia (PA), 2020. ISBN: 9780323672801.
36. 36. Wolkoff AW, Berk PD. Bilirubin metabolism and jaundice. Schiff's Diseases of the Liver, Schiff ER, Maddrey WC, Reddy KR (Eds). Wiley, Hoboken (NJ), 2017; s. 103-134. doi:10.1002/9781119251316.ch5.
37. 37. Ravindran RR. Jaundice. Surgery (Oxford). 2020; 38(8):446-452. doi:10.1016/j.mpsur.2020.06.008.
38. 38. Ivanov A, Semenova E. Gilbert's syndrome, bilirubin level and UGT1A1∗28 genotype in men of North-West region of Russia. J Clin Exp Hepatol. 2021; 11(6):691-697. doi:10.1016/j.jceh.2021.01.006.
39. 39. Lorente S, Hautefeuille M, Sanchez-Cedillo A. The liver, a functionalized vascular structure. Sci Rep. 2020; 10(1):16194. doi:10.1038/s41598-020-73208-8.
40. 40. Guyton AC, Hall JE. Medical Physiology. W.B. Saunders Company, Philadelphia (PA), 1996. Çev. Çavuşoğlu GN, Nobel Tıp Kitabevi, İstanbul, 2006. ISBN: 9780323672801.
41. 41. Sumadewi KT. Embryology, anatomy and physiology of the liver. Indian J Clin Anat Physiol. 2023; 10(3):138-144. doi:10.18231/j.ijcap.2023.031.
42. 42. Kenny LC, McCrae KR, Cunningham FG. Platelets, coagulation, and the liver. Chesley’s Hypertensive Disorders in Pregnancy, Taylor RN, Roberts JM, Lindheimer MD (Eds). Springer, Cham, 2015; s. 379-396. doi:10.1016/B978-0-12-407866-6.00017-1.
43. 43. Bati B, Celik I, Turan A, Eray N, et al. Effect of isgin (Rheum ribes L.) on biochemical parameters, antioxidant activity and DNA damage in rats with obesity induced with high-calorie diet. Arch Physiol Biochem. 2023;129 (2):298-306. doi:10.1080/13813455.2021.1999515.
44. 44. Gyamfi D, Danquah KO. Nutrients and liver metabolism. Molecular Aspects of Alcohol and Nutrition, Patel VB (Ed). Academic Press, London, 2016; s. 3-15. doi:10.1016/B978-0-12-800773-0.00001-X.
45. 45. Nguyen PT, Leray V, Diez M, et al. Liver lipid metabolism. J Anim Physiol Anim Nutr. 2008; 92(3):272-283. doi:10.1111/j.1439-0396.2007.00752.x.
46. 46. Kennelly PJ, Murray RK, Jacob M, et al. Plasma proteins & immunoglobulins. Harper’s Illustrated Biochemistry, Rodwell VW, Bender DA, Botham KM, Kennelly PJ, Weil PA (Eds), 31st ed. McGraw-Hill, New York, 2015; s. 1529-1559.
47. 47. Aronica L, Ordovas JM, Volkov A, et al. Genetic biomarkers of metabolic detoxification for personalized lifestyle medicine. Nutrients. 2022; 14(4):768. doi:10.3390/nu14040768.
48. 48. Mohsin NA, Farrukh M, Shahzadi S, et al. Drug metabolism: Phase I and Phase II metabolic pathways. Drug Metabolism and Pharmacokinetics, Rudrapal M (Ed). IntechOpen, London, 2024; s. 1-16. doi:10.5772/intechopen.112854.
49. 49. Li A, Zhang J, Zhang X, et al. Angiotensin II induces connective tissue growth factor expression in human hepatic stellate cells by a transforming growth factor β-independent mechanism. Sci Rep. 2017; 7(1):1-18. doi:10.1038/s41598-017-08334-x.
50. 50. Jiang Y, Zhang T, Kusumanchi P, et al. Alcohol metabolizing enzymes, microsomal ethanol oxidizing system, cytochrome P450 2E1, catalase, and aldehyde dehydrogenase in alcohol-associated liver disease. Biomedicines. 2020; 8(3):50. doi:10.3390/biomedicines8030050.
51. 51. Rahal A, Kumar A, Singh V, et al. Oxidative stress, prooxidants, and antioxidants: the interplay. Biomed Res Int. 2014; 2014:761264. doi:10.1155/2014/761264.
52. 52. Wiss O, Weber F. The liver and vitamins. The Liver: Morphology, Biochemistry, Physiology, Iber FL (Ed). Springer, New York, 1964; s. 145-162. ISBN: 9781483251523.
53. 53. Yatkın G, Gültekin SK, Albayrak İG, et al. Beyin homeostazında bakır, demir, çinko elementlerinin Parkinson hastalığı ile ilişkisi. Doğu Fen Bilimleri Derg. 2022; 5(2):1-11. doi:10.57244/dfbd.1073262.
54. 54. Kubes P, Jenne C. Immune responses in the liver. Annu Rev Immunol. 2018; 36:247-277. doi:10.1146/annurev-immunol-051116-052415.
55. 55. Gálvez NM, Bohmwald K, Pacheco GA, et al. Type I natural killer T cells as key regulators of the immune response to infectious diseases. Clin Microbiol Rev. 2021; 34(2):e00112-21. doi:10.1128/CMR.00112-21.
56. 56. Ehlting C, Wolf SD, Bode JG. Acute-phase protein synthesis: a key feature of innate immune functions of the liver. Biol Chem. 2021; 402(9):1129-1145. doi:10.1515/hsz-2021-0209