كيمياء سريريه نظري 6 PDF

University Of AL Mashreq Liver function College Of Pharmacy Dilan Zakaria C l i n i c a l P h a r m a c y S p e c i a l i s t ( F I B...

University Of AL Mashreq Liver function College Of Pharmacy Dilan Zakaria C l i n i c a l P h a r m a c y S p e c i a l i s t ( F I B M S ) Clinical Chemistry Functions OF The Liver The liver has essential synthetic and excretory functions and can be thought of as a large ‘metabolic factory’. It also detoxifies and, like the kidneys, excretes the end products of metabolism. The main blood supply to the liver is via the portal vein. ‫وﻇﺎﺋﻒ اﻟﻜﺒﺪ‬ ً ‫ ﻛﻤﺎ ﻳﻘﻮم‬.‫ﻛﺒﻴﺮا‬ ‫ ﻳﻘﻮم‬،‫ وﻣﺜﻞ اﻟﻜﻠﻰ‬،‫أﻳﻀﺎ ﺑﺈزاﻟﺔ اﻟﺴﻤﻮم‬ ً " ‫ﺎ‬ ‫أﻳﻀﻴ‬ ً ‫ﺎ‬ ً‫ﻣﺼﻨﻌ‬" ‫اﻋﺘﺒﺎره‬ ‫وﻳﻤﻜﻦ‬ ‫واﻹﺧﺮاج‬ ‫اﻟﺘﺮﻛﻴﺐ‬ ‫ﻓﻲ‬ ‫أﺳﺎﺳﻴﺔ‬ ‫وﻇﺎﺋﻒ‬ ‫ﻳﺆدي اﻟﻜﺒﺪ‬.‫ ﻳﺘﻢ إﻣﺪاد اﻟﻜﺒﺪ ﺑﺎﻟﺪم ﺑﺸﻜﻞ رﺋﻴﺴﻲ ﻋﻦ ﻃﺮﻳﻖ اﻟﻮرﻳﺪ اﻟﺒﺎﺑﻲ‬.‫ﺑﺈﺧﺮاج اﻟﻤﻨﺘﺠﺎت اﻟﻨﻬﺎﺋﻴﺔ ﻟﻌﻤﻠﻴﺔ اﻷﻳﺾ‬  Clinical Chemistry General Metabolic Functions When the glucose concentration is high in the portal vein, it is converted to glycogen and the carbon skeletons of fatty acids, which are transported to adipose tissue as very low- density lipoprotein (VLDL). During fasting, the systemic plasma glucose concentration is maintained by the breakdown of glycogen (glycogenolysis) or by the synthesis of glucose from substrates such as glycerol, lactate and amino acids (gluconeogenesis). Fatty acids reaching the liver from fat stores may be metabolized in the tricarboxylic acid cycle, converted to ketones or incorporated into triglycerides ‫اﻟﻮﻇﺎﺋﻒ اﻷﻳﻀﻴﺔ اﻟﻌﺎﻣﺔ‬ ‫ واﻟﺘﻲ‬،‫ ﻓﺈﻧﻪ ﻳﺘﺤﻮل إﻟﻰ ﺟﻠﻴﻜﻮﺟﻴﻦ وﻫﻴﺎﻛﻞ ﻛﺮﺑﻮﻧﻴﺔ ﻟﻸﺣﻤﺎض اﻟﺪﻫﻨﻴﺔ‬،‫ﻋﻨﺪﻣﺎ ﻳﻜﻮن ﺗﺮﻛﻴﺰ اﻟﺠﻠﻮﻛﻮز ﻣﺮﺗﻔﻌً ﺎ ﻓﻲ اﻟﻮرﻳﺪ اﻟﺒﺎﺑﻲ‬ ‫ ﻳﺘﻢ اﻟﺤﻔﺎظ ﻋﻠﻰ ﺗﺮﻛﻴﺰ‬،‫ أﺛﻨﺎء اﻟﺼﻴﺎم‬.(VLDL) ‫ﻳﺘﻢ ﻧﻘﻠﻬﺎ إﻟﻰ اﻷﻧﺴﺠﺔ اﻟﺪﻫﻨﻴﺔ ﻋﻠﻰ ﻫﻴﺌﺔ ﺑﺮوﺗﻴﻦ دﻫﻨﻲ ﻣﻨﺨﻔﺾ اﻟﻜﺜﺎﻓﺔ ﺟﺪً ا‬ ‫اﻟﺠﻠﻮﻛﻮز ﻓﻲ اﻟﺒﻼزﻣﺎ اﻟﺠﻬﺎزي ﻋﻦ ﻃﺮﻳﻖ ﺗﺤﻠﻞ اﻟﺠﻠﻴﻜﻮﺟﻴﻦ )ﺗﺤﻠﻞ اﻟﺠﻠﻴﻜﻮﺟﻴﻦ( أو ﻋﻦ ﻃﺮﻳﻖ ﺗﺨﻠﻴﻖ اﻟﺠﻠﻮﻛﻮز ﻣﻦ رﻛﺎﺋﺰ ﻣﺜﻞ‬ ‫ ﻳﻤﻜﻦ اﺳﺘﻘﻼب اﻷﺣﻤﺎض اﻟﺪﻫﻨﻴﺔ اﻟﺘﻲ ﺗﺼﻞ إﻟﻰ اﻟﻜﺒﺪ ﻣﻦ ﻣﺨﺎزن‬.(‫اﻟﺠﻠﺴﺮﻳﻦ واﻟﻼﻛﺘﺎت واﻷﺣﻤﺎض اﻷﻣﻴﻨﻴﺔ )ﺗﻜﻮﻳﻦ اﻟﺠﻠﻮﻛﻮز‬ ‫ أو ﺗﺤﻮﻳﻠﻬﺎ إﻟﻰ ﻛﻴﺘﻮﻧﺎت أو دﻣﺠﻬﺎ ﻓﻲ اﻟﺪﻫﻮن اﻟﺜﻼﺛﻴﺔ‬،‫اﻟﺪﻫﻮن ﻓﻲ دورة ﺣﻤﺾ ﺛﻼﺛﻲ اﻟﻜﺮﺑﻮﻛﺴﻴﻞ‬ Clinical Chemistry Synthetic Functions Hepatocytes synthesize: Plasma proteins ex. albumin, globulin and etc., excluding immunoglobulins and complement, Most coagulation factors, including fibrinogen and factors II (prothrombin), V, VII, IX, X, XI, XII and XIII – of these, prothrombin (II) and factors VII, IX and X cannot be synthesized without vitamin K, Primary bile acids, The lipoproteins, such as VLDL and high-density lipoprotein (HDL) ‫اﻟﻮﻇﺎﺋﻒ اﻟﺘﺮﻛﻴﺒﻴﺔ‬ ‫ ﺑﺎﺳﺘﺜﻨﺎء اﻟﻐﻠﻮﺑﻮﻟﻴﻨﺎت اﻟﻤﻨﺎﻋﻴﺔ‬،‫ ﺑﺮوﺗﻴﻨﺎت اﻟﺒﻼزﻣﺎ ﻣﺜﻞ اﻷﻟﺒﻮﻣﻴﻦ واﻟﻐﻠﻮﺑﻴﻮﻟﻴﻦ وﻣﺎ إﻟﻰ ذﻟﻚ‬:‫ﺗﻘﻮم اﻟﺨﻼﻳﺎ اﻟﻜﺒﺪﻳﺔ ﺑﺘﺨﻠﻴﻖ‬ ،‫واﻟﻤﻜﻤﻼت‬ ‫ ﻻ ﻳﻤﻜﻦ‬،‫ ﻣﻦ ﺑﻴﻨﻬﺎ‬- XIII‫ و‬V، VII، IX، X، XI، XII ،(‫ )اﻟﺒﺮوﺛﺮوﻣﺒﻴﻦ‬II ‫ ﺑﻤﺎ ﻓﻲ ذﻟﻚ اﻟﻔﻴﺒﺮﻳﻨﻮﺟﻴﻦ واﻟﻌﻮاﻣﻞ‬،‫ ﻣﻌﻈﻢ ﻋﻮاﻣﻞ اﻟﺘﺨﺜﺮ‬ ،K ‫ ﺑﺪون ﻓﻴﺘﺎﻣﻴﻦ‬X‫ و‬VII، IX ‫( واﻟﻌﻮاﻣﻞ‬II) ‫ﺗﺨﻠﻴﻖ اﻟﺒﺮوﺛﺮوﻣﺒﻴﻦ‬ (HDL ) ‫ واﻟﺒﺮوﺗﻴﻦ اﻟﺪﻫﻨﻲ ﻋﺎﻟﻲ اﻟﻜﺜﺎﻓﺔ‬VLDL ‫ ﻣﺜﻞ‬،‫ اﻟﺒﺮوﺗﻴﻨﺎت اﻟﺪﻫﻨﻴﺔ‬،‫ اﻷﺣﻤﺎض اﻟﺼﻔﺮاوﻳﺔ اﻷوﻟﻴﺔ‬ Clinical Chemistry Synthetic Functions The liver has a very large functional reserve. Deficiencies in synthetic function can be detected only if liver disease is extensive. Before a fall in plasma albumin concentration is attributed to advanced liver disease, extrahepatic causes must be excluded, such as the loss of protein through the kidney, gut or skin, or across capillary membranes into the interstitial space, as in even mild inflammation or infection. ‫اﻟﻮﻇﺎﺋﻒ اﻻﺻﻄﻨﺎﻋﻴﺔ‬ ‫ وﻻ ﻳﻤﻜﻦ اﻛﺘﺸﺎف أوﺟﻪ اﻟﻘﺼﻮر ﻓﻲ اﻟﻮﻇﻴﻔﺔ اﻻﺻﻄﻨﺎﻋﻴﺔ إﻻ إذا ﻛﺎن ﻣﺮض اﻟﻜﺒﺪ‬.‫ﻳﺘﻤﺘﻊ اﻟﻜﺒﺪ ﺑﺎﺣﺘﻴﺎﻃﻲ وﻇﻴﻔﻲ ﻛﺒﻴﺮ ﻟﻠﻐﺎﻳﺔ‬ ‫ ﻣﺜﻞ‬،‫ ﻳﺠﺐ اﺳﺘﺒﻌﺎد اﻷﺳﺒﺎب ﺧﺎرج اﻟﻜﺒﺪ‬،‫ وﻗﺒﻞ أن ﻳُﻌﺰى اﻧﺨﻔﺎض ﺗﺮﻛﻴﺰ أﻟﺒﻮﻣﻴﻦ اﻟﺒﻼزﻣﺎ إﻟﻰ ﻣﺮض اﻟﻜﺒﺪ اﻟﻤﺘﻘﺪم‬.‫واﺳﻊ اﻟﻨﻄﺎق‬ ‫ ﻛﻤﺎ ﻫﻮ اﻟﺤﺎل ﻓﻲ اﻻﻟﺘﻬﺎب أو‬،‫ أو ﻋﺒﺮ اﻷﻏﺸﻴﺔ اﻟﺸﻌﺮﻳﺔ إﻟﻰ اﻟﺤﻴﺰ اﻟﺨﻼﻟﻲ‬،‫ﻓﻘﺪان اﻟﺒﺮوﺗﻴﻦ ﻣﻦ ﺧﻼل اﻟﻜﻠﻰ أو اﻷﻣﻌﺎء أو اﻟﺠﻠﺪ‬.‫اﻟﻌﺪوى اﻟﺨﻔﻴﻔﺔ‬ Clinical Chemistry Synthetic Functions Prothrombin levels, assessed by measuring the prothrombin time, may be reduced because of impaired hepatic synthesis, whether due to failure to absorb vitamin K or to hepatocellular damage. If hepatocellular function is adequate, parenteral administration of vitamin K may reverse the abnormality. ‫اﻟﻮﻇﺎﺋﻒ اﻟﺘﺮﻛﻴﺒﻴﺔ‬ ‫ ﺳﻮاء‬،‫ ﺑﺴﺒﺐ ﺿﻌﻒ ﺗﺨﻠﻴﻖ اﻟﻜﺒﺪ‬،‫ اﻟﺘﻲ ﻳﺘﻢ ﺗﻘﻴﻴﻤﻬﺎ ﻋﻦ ﻃﺮﻳﻖ ﻗﻴﺎس زﻣﻦ اﻟﺒﺮوﺛﺮوﻣﺒﻴﻦ‬،‫ﻗﺪ ﺗﻨﺨﻔﺾ ﻣﺴﺘﻮﻳﺎت اﻟﺒﺮوﺛﺮوﻣﺒﻴﻦ‬ ‫ ﻓﻘﺪ ﻳﺆدي إﻋﻄﺎء ﻓﻴﺘﺎﻣﻴﻦ‬،‫ إذا ﻛﺎﻧﺖ وﻇﻴﻔﺔ اﻟﺨﻼﻳﺎ اﻟﻜﺒﺪﻳﺔ ﻛﺎﻓﻴﺔ‬.‫ﺑﺴﺒﺐ اﻟﻔﺸﻞ ﻓﻲ اﻣﺘﺼﺎص ﻓﻴﺘﺎﻣﻴﻦ ك أو ﺗﻠﻒ اﻟﺨﻼﻳﺎ اﻟﻜﺒﺪﻳﺔ‬.‫ك ﻋﻦ ﻃﺮﻳﻖ اﻟﺤﻘﻦ إﻟﻰ ﻋﻜﺲ اﻟﺨﻠﻞ‬  Clinical Chemistry Excretion and detoxification The excretion of bilirubin Other substances that are inactivated and excreted by the liver include the following: Cholesterol – excreted in the bile either unchanged or after conversion to bile acids. Amino acids – which are deaminated in the liver. Amino groups, and the ammonia produced by intestinal bacterial action and absorbed into the portal vein, are converted to urea. Steroid hormones – which are metabolized and inactivated by conjugation with glucuronate and sulphate and excreted in the urine in these water- soluble forms. ‫اﻹﺧﺮاج وإزاﻟﺔ اﻟﺴﻤﻮم‬ ‫ ﻳﺘﻢ إﻓﺮازه ﻓﻲ اﻟﺼﻔﺮاء إﻣﺎ‬- ‫ اﻟﻜﻮﻟﻴﺴﺘﺮول‬:‫إﺧﺮاج اﻟﺒﻴﻠﻴﺮوﺑﻴﻦ ﺗﺸﻤﻞ اﻟﻤﻮاد اﻷﺧﺮى اﻟﺘﻲ ﻳﺘﻢ ﺗﻌﻄﻴﻠﻬﺎ وإﺧﺮاﺟﻬﺎ ﻣﻦ اﻟﻜﺒﺪ ﻣﺎ ﻳﻠﻲ‬ ‫ ﻳﺘﻢ ﺗﺤﻮﻳﻞ اﻟﻤﺠﻤﻮﻋﺎت‬.‫ اﻟﺘﻲ ﻳﺘﻢ ﻧﺰع أﻣﻴﻨﻬﺎ ﻓﻲ اﻟﻜﺒﺪ‬- ‫ اﻷﺣﻤﺎض اﻷﻣﻴﻨﻴﺔ‬.‫دون ﺗﻐﻴﻴﺮ أو ﺑﻌﺪ ﺗﺤﻮﻳﻠﻪ إﻟﻰ أﺣﻤﺎض ﺻﻔﺮاوﻳﺔ‬.‫اﻷﻣﻴﻨﻴﺔ واﻷﻣﻮﻧﻴﺎ اﻟﻨﺎﺗﺠﺔ ﻋﻦ ﻋﻤﻞ اﻟﺒﻜﺘﻴﺮﻳﺎ اﻟﻤﻌﻮﻳﺔ واﻟﺘﻲ ﻳﺘﻢ اﻣﺘﺼﺎﺻﻬﺎ ﻓﻲ اﻟﻮرﻳﺪ اﻟﺒﺎﺑﻲ إﻟﻰ ﻳﻮرﻳﺎ‬ ‫ اﻟﺘﻲ ﻳﺘﻢ اﺳﺘﻘﻼﺑﻬﺎ وﺗﻌﻄﻴﻠﻬﺎ ﻋﻦ ﻃﺮﻳﻖ اﻻﻗﺘﺮان ﻣﻊ اﻟﺠﻠﻮﻛﻮروﻧﺎت واﻟﻜﺒﺮﻳﺘﺎت وﺗﻔﺮز ﻓﻲ اﻟﺒﻮل ﻓﻲ‬- ‫ اﻟﻬﺮﻣﻮﻧﺎت اﻟﺴﺘﻴﺮوﻳﺪﻳﺔ‬.‫ﻫﺬه اﻷﺷﻜﺎل اﻟﻘﺎﺑﻠﺔ ﻟﻠﺬوﺑﺎن ﻓﻲ اﻟﻤﺎء‬ Clinical Chemistry Excretion and detoxification Many drugs – which are metabolized and inactivated by enzymes of the endoplasmic reticulum system; some are excreted in the bile. Toxins – the reticuloendothelial Kupffer cells in the hepatic sinusoids are well placed to extract toxic substances that have been absorbed from the gastrointestinal tract. ‫اﻹﺧﺮاج وإزاﻟﺔ اﻟﺴﻤﻮم‬ ‫ واﻟﺘﻲ ﻳﺘﻢ اﺳﺘﻘﻼﺑﻬﺎ وﺗﻌﻄﻴﻠﻬﺎ ﺑﻮاﺳﻄﺔ إﻧﺰﻳﻤﺎت ﻧﻈﺎم اﻟﺸﺒﻜﺔ اﻹﻧﺪوﺑﻼزﻣﻴﺔ؛ وﺑﻌﻀﻬﺎ ﻳﻔﺮز ﻓﻲ‬- ‫ اﻟﻌﺪﻳﺪ ﻣﻦ اﻷدوﻳﺔ‬.‫اﻟﺼﻔﺮاء‬ ‫ اﻟﺨﻼﻳﺎ اﻟﺸﺒﻜﻴﺔ اﻟﺒﻄﺎﻧﻴﺔ ﻛﻮﺑﻔﺮ ﻓﻲ اﻟﺠﻴﻮب اﻷﻧﻔﻴﺔ اﻟﻜﺒﺪﻳﺔ ﻟﺪﻳﻬﺎ اﻟﻘﺪرة ﻋﻠﻰ اﺳﺘﺨﺮاج اﻟﻤﻮاد اﻟﺴﺎﻣﺔ اﻟﺘﻲ‬- ‫ اﻟﺴﻤﻮم‬.‫ﺗﻢ اﻣﺘﺼﺎﺻﻬﺎ ﻣﻦ اﻟﺠﻬﺎز اﻟﻬﻀﻤﻲ‬ Clinical Chemistry Excretion and detoxification Efficient excretion of the end products of metabolism and of bilirubin depends on: Normally functioning liver cells, Normal blood flow through the liver, Patent biliary ducts. ‫اﻹﺧﺮاج وإزاﻟﺔ اﻟﺴﻤﻮم‬ ‫ ﺧﻼﻳﺎ‬:‫ﻳﻌﺘﻤﺪ اﻹﺧﺮاج اﻟﻔﻌﺎل ﻟﻠﻤﻨﺘﺠﺎت اﻟﻨﻬﺎﺋﻴﺔ ﻟﻌﻤﻠﻴﺔ اﻟﺘﻤﺜﻴﻞ اﻟﻐﺬاﺋﻲ واﻟﺒﻴﻠﻴﺮوﺑﻴﻦ ﻋﻠﻰ‬.‫ اﻟﻘﻨﻮات اﻟﺼﻔﺮاوﻳﺔ اﻟﺴﻠﻴﻤﺔ‬،‫ ﺗﺪﻓﻖ اﻟﺪم اﻟﻄﺒﻴﻌﻲ ﻋﺒﺮ اﻟﻜﺒﺪ‬،‫اﻟﻜﺒﺪ اﻟﻌﺎﻣﻠﺔ ﺑﺸﻜﻞ ﻃﺒﻴﻌﻲ‬.‫ ﻓﻲ اﻟﻤﻘﺎم اﻷول ﻓﻲ اﻟﻄﺤﺎل‬،‫ﻳﺘﻢ ﺗﻜﺴﻴﺮ ﺧﻼﻳﺎ اﻟﺪم اﻟﺤﻤﺮاء ﺑﻮاﺳﻄﺔ اﻟﺠﻬﺎز اﻟﺸﺒﻜﻲ اﻟﺒﻄﺎﻧﻲ‬ ‫ واﻟﺬي ﻳﺘﺤﻮل إﻟﻰ ﺑﻴﻠﻴﺮوﺑﻴﻦ ﺑﻌﺪ‬،‫ واﻟﻬﻴﻢ‬،‫ واﻟﺬي ﻳﺪﺧﻞ إﻟﻰ ﻣﺠﻤﻮﻋﺔ اﻟﺒﺮوﺗﻴﻦ اﻟﻌﺎﻣﺔ‬،‫ ﻳﻨﻘﺴﻢ اﻟﻬﻴﻤﻮﺟﻠﻮﺑﻴﻦ إﻟﻰ ﻏﻠﻮﺑﻴﻦ‬.‫إزاﻟﺔ اﻟﺤﺪﻳﺪ وإﻋﺎدة اﺳﺘﺨﺪاﻣﻪ‬ ‫ ﻣﻦ اﻟﺒﻴﻠﻴﺮوﺑﻴﻦ ﻣﻦ ﺗﻜﺴﻴﺮ اﻟﻬﻴﻢ ﻓﻲ اﻟﺠﻬﺎز اﻟﺸﺒﻜﻲ اﻟﺒﻄﺎﻧﻲ؛ وﺗﺸﻤﻞ اﻟﻤﺼﺎدر اﻷﺧﺮى ﺗﻜﺴﻴﺮ ﺧﻼﻳﺎ اﻟﺪم‬٪80 ‫ ﻳﻨﺸﺄ ﺣﻮاﻟﻲ‬ Clinical Chemistry.‫اﻟﺤﻤﺮاء ﻏﻴﺮ اﻟﻨﺎﺿﺠﺔ ﻓﻲ ﻧﺨﺎع اﻟﻌﻈﺎم واﻟﻤﺮﻛﺒﺎت ذات اﻟﺼﻠﺔ ﻣﺜﻞ اﻟﻤﻴﻮﻏﻠﻮﺑﻴﻦ واﻟﺴﻴﺘﻮﻛﺮوم‬ Formation and excretion of Bilirubin Red blood cells are broken down by the reticuloendothelial system, primarily in the spleen. Hemoglobin is split into globin, which enters the general protein pool, and heme, which is converted to bilirubin after iron is removed and reused. Around 80% of bilirubin originates from heme breakdown in the reticuloendothelial system; other sources include immature red cell breakdown in the bone marrow and related compounds like myoglobin and cytochromes. Less than 300 μmol of bilirubin is produced daily, while the liver can conjugate up to 1 mmol/day, making hyperbilirubinemia an unreliable indicator of liver disease. Unconjugated bilirubin is transported to the liver bound to albumin; it is lipid-soluble and potentially toxic but normally protein-bound at physiological levels. ‫ ﻓﻲ ﺣﻴﻦ ﻳﻤﻜﻦ ﻟﻠﻜﺒﺪ أن ﻳﻘﺘﺮن ﺑﻤﺎ ﻳﺼﻞ إﻟﻰ‬،‫ﻳﻮﻣﻴﺎ‬ 1 ً ‫ ﻣﻴﻜﺮوﻣﻮل ﻣﻦ اﻟﺒﻴﻠﻴﺮوﺑﻴﻦ‬300 ‫ﻳﺘﻢ إﻧﺘﺎج أﻗﻞ ﻣﻦ‬.‫ﻣﺆﺷﺮا ﻏﻴﺮ ﻣﻮﺛﻮق ﺑﻪ ﻷﻣﺮاض اﻟﻜﺒﺪ‬ ً ‫ ﻣﻤﺎ ﻳﺠﻌﻞ ﻓﺮط ﺑﻴﻠﻴﺮوﺑﻴﻦ اﻟﺪم‬،‫ ﻳﻮم‬/ ‫ﻣﻠﻴﻤﻮل‬ ‫ﺳﺎﻣﺎ‬ ً ‫ﻣﺮﺗﺒﻄﺎ ﺑﺎﻷﻟﺒﻮﻣﻴﻦ؛ وﻫﻮ ﻗﺎﺑﻞ ﻟﻠﺬوﺑﺎن ﻓﻲ اﻟﺪﻫﻮن وﻗﺪ ﻳﻜﻮن‬ ً ‫ ﻳﺘﻢ ﻧﻘﻞ اﻟﺒﻴﻠﻴﺮوﺑﻴﻦ ﻏﻴﺮ اﻟﻤﻘﺘﺮن إﻟﻰ اﻟﻜﺒﺪ‬.‫وﻟﻜﻨﻪ ﻳﺮﺗﺒﻂ ﻋﺎد ًة ﺑﺎﻟﺒﺮوﺗﻴﻦ ﻋﻠﻰ اﻟﻤﺴﺘﻮﻳﺎت اﻟﻔﺴﻴﻮﻟﻮﺟﻴﺔ‬ Clinical Chemistry Formation and excretion of Bilirubin Approximately 300 μmol of bilirubin reaches the liver daily, where it is transferred from albumin to hepatocytes. Bilirubin binds to ligandin (Y protein) in hepatocytes, is transported to the smooth endoplasmic reticulum, and conjugated with glucuronate by uridine diphosphate glucuronyl transferase. Conjugated bilirubin is secreted into bile canaliculi, a process dependent on bile acid secretion, which can be impaired by liver damage or increased biliary pressure. Drugs and other anions may compete with bilirubin for ligandin binding, potentially inhibiting conjugation and excretion. Novobiocin inhibits glucuronyl transferase, worsening unconjugated hyperbilirubinemia. ‫ﺗﻜﻮﻳﻦ اﻟﺒﻴﻠﻴﺮوﺑﻴﻦ وإﺧﺮاﺟﻪ‬.‫ ﺣﻴﺚ ﻳﺘﻢ ﻧﻘﻠﻪ ﻣﻦ اﻷﻟﺒﻮﻣﻴﻦ إﻟﻰ اﻟﺨﻼﻳﺎ اﻟﻜﺒﺪﻳﺔ‬،‫ﻳﻮﻣﻴﺎ‬ ً ‫اﻟﻜﺒﺪ‬ ‫إﻟﻰ‬ ‫اﻟﺒﻴﻠﻴﺮوﺑﻴﻦ‬ ‫ﻣﻦ‬ ‫ﻣﻴﻜﺮوﻣﻮل‬ 300 ‫ ﻳﺼﻞ ﺣﻮاﻟﻲ‬ ‫ وﻳﺮﺗﺒﻂ ﺑﺎﻟﺠﻠﻮﻛﻮروﻧﺎت‬،‫ وﻳﻨﺘﻘﻞ إﻟﻰ اﻟﺸﺒﻜﺔ اﻹﻧﺪوﺑﻼزﻣﻴﺔ اﻟﻤﻠﺴﺎء‬،‫( ﻓﻲ اﻟﺨﻼﻳﺎ اﻟﻜﺒﺪﻳﺔ‬Y ‫ ﻳﺮﺗﺒﻂ اﻟﺒﻴﻠﻴﺮوﺑﻴﻦ ﺑﺎﻟﻠﻴﺠﺎﻧﺪﻳﻦ )ﺑﺮوﺗﻴﻦ‬.‫ﺑﻮاﺳﻄﺔ ﻳﻮرﻳﺪﻳﻦ ﺛﻨﺎﺋﻲ ﻓﻮﺳﻔﺎت ﺟﻠﻮﻛﻮروﻧﻴﻞ ﺗﺮاﻧﺴﻔﻴﺮاز‬ ‫ واﻟﺘﻲ ﻳﻤﻜﻦ أن ﺗﺘﺄﺛﺮ ﺑﺘﻠﻒ‬،‫ وﻫﻲ ﻋﻤﻠﻴﺔ ﺗﻌﺘﻤﺪ ﻋﻠﻰ إﻓﺮاز اﻷﺣﻤﺎض اﻟﺼﻔﺮاوﻳﺔ‬،‫ ﻳﺘﻢ إﻓﺮاز اﻟﺒﻴﻠﻴﺮوﺑﻴﻦ اﻟﻤﻘﺘﺮن ﻓﻲ اﻟﻘﻨﻮات اﻟﺼﻔﺮاوﻳﺔ‬.‫اﻟﻜﺒﺪ أو زﻳﺎدة اﻟﻀﻐﻂ اﻟﺼﻔﺮاوي‬ ‫ ﻳﺜﺒﻂ‬.‫ ﻣﻤﺎ ﻗﺪ ﻳﺆدي إﻟﻰ ﺗﺜﺒﻴﻂ اﻻﻗﺘﺮان واﻹﺧﺮاج‬،‫ ﻗﺪ ﺗﺘﻨﺎﻓﺲ اﻷدوﻳﺔ واﻷﻧﻴﻮﻧﺎت اﻷﺧﺮى ﻣﻊ اﻟﺒﻴﻠﻴﺮوﺑﻴﻦ ﻋﻠﻰ ارﺗﺒﺎط اﻟﻠﻴﺠﺎﻧﺪﻳﻦ‬.‫ ﻣﻤﺎ ﻳﺆدي إﻟﻰ ﺗﻔﺎﻗﻢ ﻓﺮط ﺑﻴﻠﻴﺮوﺑﻴﻦ اﻟﺪم ﻏﻴﺮ اﻟﻤﻘﺘﺮن‬،‫ﻧﻮﻓﻮﺑﻴﻮﺳﻴﻦ ﺟﻠﻮﻛﻮروﻧﻴﻞ ﺗﺮاﻧﺴﻔﻴﺮاز‬ Question