高鑫內(nèi)分泌總論課件

1、內(nèi)分泌系統(tǒng)疾病總 論Introduction to Endocrinology and Metabolic Diseases 復(fù)旦大學(xué)附屬中山醫(yī)院內(nèi)分泌科 高鑫1內(nèi)分泌系統(tǒng)疾病總 論IntroductionHistory and development of Endocrinology (1)Roughly a hundred years ago, Starling coined the term hormone to describe secretin, a substance secreted by the small intestine into the blood stream to

2、stimulate pancreatic secretion. In his Croonian Lectures, Starling considered the endo- crine and nervous systems as two distinct mechanisms for coordination and control of organ function. Thus, endocrinology found its first home in the discipline of mammalian physiology.2History and development of

3、EndWork over the next several decades by biochemists, physiologists, and clinical investigators led to the characterization of many hormones secreted into the blood stream from discrete glands or other organs. These investigators showed for the first time that diseases such as hypothyroidism and dia

4、betes could be treated successfully by replacing specific hormones. These initial triumphs formed the foundation of the clinical specialty of endocrinology.History and development of Endocrinology (2)3Work over the next several decAdvances in cell biology, molecular biology, and genetics over the en

5、suing years began to help explain the mechanisms of endocrine diseases and of hormone secretion and action. Although these advances have embedded endocrinology into the framework of molecular cell biology, they have not changed the essential subject of endocrinology _the signaling that coordinates a

6、nd controls the functions of multiple organs and processes. History and development of Endocrinology (2)4Advances in cell biology, moleHormone formation may occur either in localized collections of specific cells, in the endocrine glands, or in cells that have additional roles.Many protein hormones:

7、 growth hormone? parathyroid hormone? prolactin? insulin? glucagon? Leptin?Formation of small hormone molecules initiates with commonly found Precursors: Such as: adrenals, gonads, or thyroid.In the case of the steroid hormones, the precursor is cholesterol, which is modified by various hydroxylatio

8、ns, methylations, and demethylations to form the glucocorticoids, androgens, and estrogens.In contrast, the precursor of vitamin D, 7-dehydrocholesterol, is produced in skin keratinocytes, again from cholesterol, by a photochemical reaction. ENDOCRINE GLANDS5Hormone formation may occur ei 內(nèi)分泌系統(tǒng)內(nèi)分泌腺臟

9、器內(nèi)分泌組織激素體液調(diào)節(jié)系統(tǒng)（包括旁分泌、自分泌）代謝過(guò)程臟器功能生長(zhǎng)發(fā)育生殖衰老Endocrine System6 內(nèi)分泌系統(tǒng)內(nèi)分泌腺臟器內(nèi)分泌組織激素代謝過(guò)程臟器功能生長(zhǎng)發(fā)內(nèi)分泌學(xué)發(fā)展三階段腺體內(nèi)分泌學(xué) Organic Endocrinology組織內(nèi)分泌學(xué) Histological Endocrinology分子內(nèi)分泌學(xué) Moleculer Endocrinology7內(nèi)分泌學(xué)發(fā)展三階段腺體內(nèi)分泌學(xué)7激素的種類(lèi)Hormones 肽類(lèi)/蛋白類(lèi)激素 （Protein or peptide) : ACTH,LH, FSH, PHT, TSH, Insulun ,Glucagon, IGFs氨基

10、酸衍生物（Amino Acid derivatives)： 兒茶酚胺類(lèi)（腎上腺素、去甲腎上腺素）脂肪酸衍生物(Fatty acid derivatives ): 前列腺素類(lèi)、視黃酸 膽固醇衍生物（Cholesterol derivatives )： 考的松， 醛固酮、1,25(OH)2 D3性激素8激素的種類(lèi)肽類(lèi)/蛋白類(lèi)激素 （Protein or pept激素的作用機(jī)制（1） 與膜受體結(jié)合 G蛋白偶聯(lián) 發(fā)揮生物效應(yīng) （肽類(lèi)激素、生物胺、前列腺素） 與膜受體結(jié)合 受體自身磷酸化 發(fā)揮生物學(xué)效應(yīng) （酪氨酸激酶） （生長(zhǎng)因子家族、Insulin , IGFs)與核受體結(jié)合 與DNA特異序列結(jié)合 功

11、能蛋白轉(zhuǎn)錄 （甾體類(lèi)激素）9激素的作用機(jī)制（1） 與膜受體結(jié)合 G蛋白偶聯(lián) 1010G-protein-coupled 7-membrane spanning receptor11G-protein-coupled 7-membrane sG-protein-coupled 7-membrane spanning receptor12G-protein-coupled 7-membrane s131314141515激素的作用機(jī)制（2）激素信息在細(xì)胞內(nèi)的信號(hào)傳導(dǎo)Coris: 發(fā)現(xiàn)了磷酸化酶的可逆磷酸化 （無(wú)活性的磷酸化酶b/有活性的磷酸化酶a之間的互變） 獲得1951年諾貝爾獎(jiǎng)。Sutherl

12、and: 成功分離和確定的腺苷酸環(huán)化酶和磷酸二酯酶 （cAMP合成與分解的兩個(gè)關(guān)鍵酶） 提出了激素作用的第二信使學(xué)說(shuō) 獲得1971年諾貝爾生理醫(yī)學(xué)獎(jiǎng)。Krebs & Fisher: 于60年代末發(fā)現(xiàn)蛋白激酶A(PKA) （依賴(lài)cAMP , 刺激多種底物蛋白磷酸化) 闡明了PKA啟動(dòng)的磷酸化和去磷酸化途徑。 獲得1992年諾貝爾生理醫(yī)學(xué)獎(jiǎng)。 16激素的作用機(jī)制（2）激素信息在細(xì)胞內(nèi)的信號(hào)傳導(dǎo)Coris: 內(nèi)分泌系統(tǒng)的相互調(diào)節(jié)神經(jīng)-內(nèi)分泌系統(tǒng)的相互調(diào)節(jié)內(nèi)分泌系統(tǒng)的反饋調(diào)節(jié)免疫系統(tǒng)與內(nèi)分泌系統(tǒng)的關(guān)系神經(jīng)-內(nèi)分泌-免疫網(wǎng)絡(luò)調(diào)節(jié)17內(nèi)分泌系統(tǒng)的相互調(diào)節(jié)神經(jīng)-內(nèi)分泌系統(tǒng)的相互調(diào)節(jié)171818神經(jīng)-內(nèi)分泌-

13、免疫網(wǎng)絡(luò)調(diào)節(jié) （三大系統(tǒng)的共性）該網(wǎng)絡(luò)在機(jī)體全部生命活動(dòng)中有極其重要的調(diào)節(jié)作用整合作用 維持機(jī)體內(nèi)環(huán)境穩(wěn)定，抵抗外來(lái)有害因素；儲(chǔ)存和記憶信息 神經(jīng)系統(tǒng)和免疫系統(tǒng)均有記憶功能；周期性活動(dòng) 季節(jié)性、晝夜節(jié)律性；反饋調(diào)節(jié)機(jī)制年齡影響19神經(jīng)-內(nèi)分泌-免疫網(wǎng)絡(luò)調(diào)節(jié)該網(wǎng)絡(luò)在機(jī)體全部生命活動(dòng)中有極其重內(nèi)分泌疾病的分類(lèi)按病變器官分類(lèi)按功能分類(lèi)：亢進(jìn)、減退、正常；按病變部位分類(lèi)：原發(fā)性、繼發(fā)性、三發(fā)性激素分泌缺陷受體基因缺陷-激素抵抗20內(nèi)分泌疾病的分類(lèi)按病變器官分類(lèi)激素分泌缺陷20內(nèi)分泌疾病的診斷原則三大原則： 功能診斷 定位診斷 病因/病理診斷21內(nèi)分泌疾病的診斷原則三大原則：21內(nèi)分泌疾病的診斷原則功能

14、診斷癥狀、體征實(shí)驗(yàn)室資料：代謝紊亂的證據(jù)； 激素分泌異常的證據(jù)； 內(nèi)分泌功能試驗(yàn)：興奮試驗(yàn) 抑制試驗(yàn) 激發(fā)試驗(yàn) 同位素檢查 細(xì)胞學(xué)檢查 骨密度檢查22內(nèi)分泌疾病的診斷原則功能診斷癥狀、體征22內(nèi)分泌疾病的診斷原則 定位診斷同位素顯象掃描磁共振CT B超聲檢查23內(nèi)分泌疾病的診斷原則 定位診斷同位素顯象掃描23內(nèi)分泌疾病的診斷原則病因診斷 免疫學(xué)檢查 組織病理學(xué)檢查 細(xì)胞學(xué)檢查 染色體檢查 受體測(cè)定 分子生物學(xué)檢查24內(nèi)分泌疾病的診斷原則病因診斷 免疫學(xué)檢查24 內(nèi)分泌疾病的防治原則預(yù)防為主： 地方性甲狀腺腫 甲狀腺危象 腎上腺危象 低血糖反應(yīng) 黏液性水腫昏迷25 內(nèi)分泌疾病的防治原則預(yù)防為主：

15、 地方性甲狀腺腫25治療原則病因治療：垂體瘤、腎上腺腺瘤、嗜鉻細(xì)胞瘤、 甲狀旁腺腺瘤等糾正代謝紊亂：腺體功能亢進(jìn)的治療； 腺體功能減退的治療；26治療原則病因治療：垂體瘤、腎上腺腺瘤、嗜鉻細(xì)胞瘤、 26腺體功能亢進(jìn)的治療： 手術(shù)、放射治療、抑制激素合成與釋放的藥物； 化療藥物；腺體功能減退的治療： 替代治療 補(bǔ)充生理劑量的激素 甲狀腺激素、腎上腺皮質(zhì)激素、生長(zhǎng)激素等治療原則27腺體功能亢進(jìn)的治療：治療原則27How to study clinical endocrinology28How to study 28The Endocrine PatientA textbook of medicin

16、e is inevitably about disease, but the practice of medicine deals with illness.The topic of “the endocrine patient to be discussed include : initial evaluation, the nature of referral, the fact finding required in clinical evaluation, the use of the laboratory and imaging, the formulation of a diffe

17、rential diagnosis, decision making, and management. 29The Endocrine PatientA textbooMany features of being an endocrine patient are common to all experiences of illness. A few minutes spent in getting to know the patient can pay enormous dividends in the accuracy of the history obtained and in setti

18、ng the stage for further cooperation with testing and treatment.In as much as most endocrine consultation is elective rather than emergent, an experienced physician favors asking a few simple questions, such as Where are you from? What do you do? How did you come to us? Were you referred? and so on.

19、 Almost always, some common experience or acquaintance is discovered that provides the basis for a rapport that does not emerge from formal medical questioning. This step also immediately conveys that you are interested in the patient as a person and not just as a disease.General considerations30Man

20、y features of being an endoNumerous special features of endocrine disease make patient presentation quite different from that seen in general medicine. One is the discovery of abnormality through screening of asymptomatic individuals, for example: a high serum calcium level discovered through multip

21、hasic screening ; a high blood glucose level discovered in a shopping mall kiosk. The very absence of symptoms lends an unreality to the moment and should become an explicit topic of the patient-doctor interaction. In this circumstance, it is worth emphasizing the value of early discovery and preven

22、tion of greater morbidity.SPECIAL FEATURES OF ENDOCRINE ILLNESS31Numerous special features of eThe symptoms of endocrine disorders overlap a great range of normal characteristics, including: body contour, facial configurations, weight distributions, skin and hair coloring, and muscular capacity. The

23、y also overlap with other conditions that are far more common, including: depression and normal aging. The added adipose tissue of hyperadrenocorticism is more difficult to recognize in a person who is already obese. The nervousness associated with hyperthyroidism is less apparent in a thin, hyperki

24、netic man than in a person of moderate body weight.The effects of an androgen-producing adrenal tumor are less likely to be noticed in a family of swarthy, hirsute individuals.Overlap with Other Diseases (1)32The symptoms of endocrine disoOverlap with Other Diseases (2)Finally, most endocrine disord

25、ers evolve gradually over months to years instead of appearing suddenly,.This combination of varied host background and slow evolution of disease leads to considerable delay in diagnosis: both the patient and primary care physician adapt to the changes as part of the person, and definitive evaluatio

26、n, now relatively easy for most disorders, is not undertaken. Hypothyroidism and acromegaly are good examples of this phenomenon. All series show a remarkable delay in diagnosis despite sometimes disabling symptoms.33Overlap with Other Diseases (2Overlap with Other Diseases (3)Hormones have more distant effects than local effects. This, of course, reflects their