胆汁酸代谢及其异常.pptx
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1、1bile pigment cholesterolinorganic salt第1页/共62页2qTo promote digestion and absorption of fatTo promote digestion and absorption of fat 促进脂肪的消化和吸收促进脂肪的消化和吸收 qTo promote the absorption of fat-soluble To promote the absorption of fat-soluble vitaminsvitamins 促进脂溶性维生素的吸收促进脂溶性维生素的吸收qRegulation of choleste
2、rol metabolism,The Regulation of cholesterol metabolism,The maintenance of cholesterol in the bile of the maintenance of cholesterol in the bile of the state of dissolutionstate of dissolution 调节胆固醇代谢调节胆固醇代谢,维持胆汁中胆固醇的溶解状态维持胆汁中胆固醇的溶解状态二、胆汁二、胆汁(主要是胆汁酸主要是胆汁酸)的功能的功能Functon of bile acid Functon of bile a
3、cid 第2页/共62页3qReduce oil/water surface tension 降低油降低油/水两相之间的水两相之间的界面张力界面张力qMake the hydrophobic lipids in aqueous micro-emulsion into a small micelle使疏水性的脂类在水相使疏水性的脂类在水相中乳化成细小的微团中乳化成细小的微团立体构象立体构象:亲水面亲水面-疏水面疏水面(较强的乳化剂)(较强的乳化剂)第3页/共62页4原料原料(precursor)precursor)precursor)precursor):胆固醇:胆固醇(cholesterolc
4、holesterolcholesterolcholesterol)部位部位(site)site)site)site):肝细胞肝细胞(liver)liver)liver)liver)种类种类(type)type)type)type):游离型、结合型游离型、结合型三、胆汁酸的代谢与功能三、胆汁酸的代谢与功能 Metabolism and function of bile acidsMetabolism and function of bile acids(一)初级胆汁酸的生物合成(一)初级胆汁酸的生物合成 Biosynthesis Biosynthesis of of primarybile ac
5、idsprimarybile acidsprimarybile acidsprimarybile acids概念(概念(concept)concept)胆固醇在肝细胞内转化生成的胆汁酸。胆固醇在肝细胞内转化生成的胆汁酸。Cholesterol in the liver cells generated into Cholesterol in the liver cells generated into bile acidsbile acids第4页/共62页5胆酸胆酸 cholic acidcholic acid鹅脱氧胆酸鹅脱氧胆酸 chenodeoxy cholic acidchenodeox
6、y cholic acid游离型游离型甘氨胆酸甘氨胆酸glycocholic acidglycocholic acid牛磺胆酸牛磺胆酸 taurocholic acidtaurocholic acid甘氨鹅脱氧胆酸甘氨鹅脱氧胆酸glycochenodeoxycholic acidglycochenodeoxycholic acid牛磺鹅脱氧胆酸牛磺鹅脱氧胆酸taurochenodeoxycholic acidtaurochenodeoxycholic acid结合型结合型第5页/共62页6第6页/共62页7部位部位(site):(site):小肠小肠(small intestine)small
7、 intestine)大肠大肠(large intestine)(large intestine)(二)次级胆汁酸的生物合成(二)次级胆汁酸的生物合成Biosynthesis second bile acidBiosynthesis second bile acid初级胆汁酸分泌到肠道后受肠道细菌作用生成的初级胆汁酸分泌到肠道后受肠道细菌作用生成的产物产物。Primary bile acid secretion by the intestinal Primary bile acid secretion by the intestinal bacterial role in post-gener
8、ated productbacterial role in post-generated product概念(概念(concept)concept):第7页/共62页8第8页/共62页97 73 312127 73 312127 77 717173 33 312122121第9页/共62页10第10页/共62页11第11页/共62页12第12页/共62页13q胆汁酸本身的负反馈调节胆汁酸本身的负反馈调节 Bile acid is a negative feedback regulationBile acid is a negative feedback regulationq甲状腺激素可促进胆
9、汁酸合成甲状腺激素可促进胆汁酸合成 Thyroid hormone may promote bile acid Thyroid hormone may promote bile acid synthesissynthesis(三)合成过程(三)合成过程(synthesis process)(synthesis process)关键酶:关键酶:7-7-羟化酶羟化酶(Hydroxylase)(Hydroxylase)调节调节(regulation)(regulation)第13页/共62页14 胆汁酸经肝细胞合成后,分泌入胆汁,进入肠道后大部分可被重吸收,经胆汁酸经肝细胞合成后,分泌入胆汁,进入肠
10、道后大部分可被重吸收,经门脉循环回到肝脏,再由肝细胞摄取,与新合成的胆汁酸一同分泌入胆汁,肠门脉循环回到肝脏,再由肝细胞摄取,与新合成的胆汁酸一同分泌入胆汁,肠-肝之间的胆汁酸循环称为胆汁酸的肠肝循环。肝之间的胆汁酸循环称为胆汁酸的肠肝循环。Bile acid synthesis by the liver cells,secreted into Bile acid synthesis by the liver cells,secreted into the bile into the intestine after most of the weight the bile into the in
11、testine after most of the weight can be absorbed through the portal vein back to can be absorbed through the portal vein back to the cycle of the liver,liver cells from the intake,the cycle of the liver,liver cells from the intake,and the synthesis of new bile acid secretion with and the synthesis o
12、f new bile acid secretion with bile into the intestines-Between the liver and bile into the intestines-Between the liver and intestine bile acid cycle known as the bile acid intestine bile acid cycle known as the bile acid enterohepatic circulation.enterohepatic circulation.概念(概念(concept)concept)四四.
13、胆汁酸的肠肝循环胆汁酸的肠肝循环 Enterohepatic circulation of bile acid第14页/共62页15有限的胆汁酸发挥最大的乳化作用有限的胆汁酸发挥最大的乳化作用;并使胆汁中胆汁酸并使胆汁中胆汁酸/胆固醇比例恒定胆固醇比例恒定,不易不易形成胆固醇结石。形成胆固醇结石。Limited Bile acids play maximize the role of the Limited Bile acids play maximize the role of the emulsion;Bile acid/cholesterol ratio constant,emulsio
14、n;Bile acid/cholesterol ratio constant,Is not easy to formIs not easy to form cholesterol gallstone.cholesterol gallstone.胆汁酸的肠肝循环胆汁酸的肠肝循环 Enterohepatic circulation of bile acid意义意义(signification)(signification)第15页/共62页16结合型胆汁酸结合型胆汁酸结合型胆汁酸结合型胆汁酸游离型胆汁酸游离型胆汁酸游离型胆汁酸游离型胆汁酸第16页/共62页17第四节第四节 肝病的生物化学代谢紊乱肝
15、病的生物化学代谢紊乱一、肝硬化的临床生物化学一、肝硬化的临床生物化学Clinical biochemistry of hepatocirrhosisClinical biochemistry of hepatocirrhosis肝硬化是一种以肝组织弥漫性纤维化、假小叶和再生肝硬化是一种以肝组织弥漫性纤维化、假小叶和再生结节形成为特征的慢性肝病。是许多肝脏疾病晚期的结节形成为特征的慢性肝病。是许多肝脏疾病晚期的共同病变。临床上有多系统受累,以肝功能减损、门共同病变。临床上有多系统受累,以肝功能减损、门脉高压两大症侯群为主要表现,晚期常出现上消化道脉高压两大症侯群为主要表现,晚期常出现上消化道出血
16、,肝性脑病,继发感染等严重的并发症。出血,肝性脑病,继发感染等严重的并发症。概念(概念(concept)Cirrhosis is a pathological diagnosis.It is characterized by widespread fibrosis with nodular regeneration.Its presence implies previous or continuing hepatic cell damage.第17页/共62页18注意:注意:肝小叶、血管结构改变,即假小叶形成。如小肝小叶、血管结构改变,即假小叶形成。如小叶结构大部分完好(先天性肝纤维化)也不是
17、叶结构大部分完好(先天性肝纤维化)也不是肝硬化。肝硬化。纤维化和结节再生必须同时存在。只有再生结节纤维化和结节再生必须同时存在。只有再生结节或纤维化不是肝硬化。(如肝门脉性硬化症没有或纤维化不是肝硬化。(如肝门脉性硬化症没有结节再生)结节再生)肝硬化的病变为弥漫性,累及整个肝脏。局部纤肝硬化的病变为弥漫性,累及整个肝脏。局部纤维化不是肝硬化。维化不是肝硬化。第18页/共62页19l常见的病因包括:常见的病因包括:l病毒性肝炎病毒性肝炎(viral hepatitis)(viral hepatitis)l酒精性肝炎酒精性肝炎(alcoholic hepatitis)(alcoholic hepa
18、titis)l胆汁郁积胆汁郁积(cholestasis)(cholestasis)l严重心力衰竭(严重心力衰竭(severe heart failure)severe heart failure)l肝豆状核变性肝豆状核变性(hepatolenticular disease)(hepatolenticular disease)l -抗胰蛋白酶缺乏症抗胰蛋白酶缺乏症(-antitrypsin deficiency)-antitrypsin deficiency)病病 因因 AetiologyAetiology引起肝硬化的病因较多,同一病因可发展为不同病理引起肝硬化的病因较多,同一病因可发展为不同病
19、理类型的肝硬化,而同一病理类型的肝硬化亦可由不同类型的肝硬化,而同一病理类型的肝硬化亦可由不同病因引起。病因引起。第19页/共62页201.1.肝硬化的生物化学机制肝硬化的生物化学机制 Cirrhosis of the biochemical mechanismsCirrhosis of the biochemical mechanisms缺氧和炎症刺激,导致胶原纤维合成增强。以缺氧和炎症刺激,导致胶原纤维合成增强。以I I型型及及型为主。型为主。Hypoxia and inflammatory stimulation,resulting in Hypoxia and inflammatory
20、 stimulation,resulting in enhanced synthesis of collagen fibers.I type in the main-and enhanced synthesis of collagen fibers.I type in the main-and.机体免疫机能不足,肝细胞反复遭受机体免疫机能不足,肝细胞反复遭受HBVHBV破坏,破坏,以及肝细胞结节状再生,纤维组织不断增生,导致以及肝细胞结节状再生,纤维组织不断增生,导致肝硬化。肝硬化。Lack of immune function,liver cells from recurring Lack
21、of immune function,liver cells from recurring destruction of HBV,as well as nodular liver cell destruction of HBV,as well as nodular liver cell regeneration,continuous proliferation of fibrous tissue,regeneration,continuous proliferation of fibrous tissue,leading to cirrhosis.leading to cirrhosis.第2
22、0页/共62页21跟跟Kuffer细胞分泌多种细胞因子及胶原酶等生细胞分泌多种细胞因子及胶原酶等生物活性物质以及储脂细胞产生胶原等有关。物活性物质以及储脂细胞产生胶原等有关。Kuffer cells with a variety of cytokines and bio-active substances,such as collagenase,as well as fat-storing cells produce collagen and so on.涉及许多遗传因素,这已成为肝细胞对损伤涉及许多遗传因素,这已成为肝细胞对损伤反应的独立病原因素。肝细胞和胆管上皮细胞反应的独立病原因素。肝细
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