腎上腺皮質(zhì)病理生理學(xué)課件

1、ADRENOCORTICAL PATHOPHYSIOLOGY 腎上腺皮質(zhì)病理生理學(xué)ADRENOCORTICAL PATHOPHYSIOLOGY The hormones(激素) of the adrenal glands(腎上腺) are essential for survival.adrenal cortex(腎上腺皮質(zhì))adrenal medulla(腎上腺髓質(zhì)) ADRENOCORTICAL PATHOPHYSIOLOGY The hormones(激素) of theADRENOCORTICAL PATHOPHYSIOLOGYThe adrenal cortex(腎上腺皮質(zhì))is t

2、he source of the two important steroid hormones(類固醇激素)Cortisol (皮質(zhì)醇) Aldosterone (醛固酮)ADRENOCORTICAL PATHOPHYSIOLOGY The adrenal medulla(腎上腺髓質(zhì)) is embryologically (胚胎學(xué)) and histologically (組織學(xué)) distinct from the cortex. It synthesizes, stores and secretes :Adrenaline(腎上腺素)Noradrenaline(去甲腎上腺素)Dopami

3、ne(多巴胺)ADRENOCORTICAL PATHOPHYSIOLOGY The adrenal medulla(腎上腺腎上腺皮質(zhì)病理生理學(xué)課件The hormones of the adrenal glandsCortisol (皮質(zhì)醇) Adrenal androgens(腎上腺雄激素)Aldosterone (醛固酮)The hormones of the adrenal glCORTISOL皮質(zhì)醇CORTISOL皮質(zhì)醇Cortisol (皮質(zhì)醇) is produced in the zona fasciculata (束狀帶 ) and zona reticularis (網(wǎng)狀帶)

4、 of the adrenal cortex.It is the end product of a series of hormones which make up thehypothalamic-pituitary-adrenocortical，HPA axis (下丘腦-垂體-腎上腺皮質(zhì)調(diào)節(jié)軸).CortisolCortisol (皮質(zhì)醇) is produced in Cortisolthe influence of cerebral factorsthe hypothalamusCorticotrophin releasing hormone (CRH) 促腎上腺皮質(zhì)激素釋放激素(AC

5、TH釋放激素)Cortisolthe influence of cerebCortisolCRHanterior pituitary 前垂體Adrenocorticotrophic hormone（ ACTH） 促腎上腺皮質(zhì)激素maintain the fascicular and reticular zones of the adrenal cortex and to stimulate the secretion of cortisol.CortisolCRH Hypothalamic secretion (下丘腦分泌 ) of CRH and pituitary secretion of

6、 ACTH are regulated by cortisol in negative feedback loops (負(fù)反饋途徑).Cortisol Hypothalamic secretion (下丘腦分腎上腺皮質(zhì)病理生理學(xué)課件ASSESSING THE FUNCTION OF THE HPA AXIS下丘腦-垂體-腎上腺調(diào)節(jié)軸功能的檢測(cè)ASSESSING THE FUNCTION OF THE Assessing of the HPA axisCortisol secretion varies widely throughout the daysingle serum measureme

7、nts are of little value in clinical practiceDynamic tests (動(dòng)態(tài)試驗(yàn)) of cortisol production form an important part of investigations of adrenocortical hyper-or hypo-functionAssessing of the HPA axisCortiDynamic tests(動(dòng)態(tài)試驗(yàn)) involving stimulation of the adrenal cortex (刺激腎上腺皮質(zhì))by synthetic ACTH (Synacthen

8、)stimulation or suppression of the whole HPA axisAssessing of the HPA axisDynamic tests(動(dòng)態(tài)試驗(yàn)) involving Adrenal cortex cells have many low-density lipoprotein receptors (LDL-R) on their surface. This enables them to take up cholesterol (膽固醇) rapidly, from which the adrenal steroid hormones are synth

9、esized.Biosynthesis of Cortisol Adrenal cortex cells have manThe conversion of cholesterol to pregnenolone (孕烯醇酮) is the rate-limiting step (限速步驟) in the biosynthesis of cortisol. This conversion is stimulated by ACTH.Biosynthesis of CortisolThe conversion of cholesterol 腎上腺皮質(zhì)病理生理學(xué)課件The Role of Cort

10、isolCortisol is an important hormone with effects on many tissues in the body. It plays a major role in metabolismThe Role of CortisolCortisol iThe Role of Cortisolpromoting protein breakdown(蛋白質(zhì)分解) in muscle and connective tissue(結(jié)締組織) the release of glycerol(甘油) and free fatty acids(游離脂肪酸) from ad

11、ipose tissue(脂肪組織). Thus, cortisol provides the substrates (底物) necessary for gluconeogenesis (葡萄糖異生) The Role of Cortisolpromoting Natural or synthetic steroids with cortisol-like effects are called glucocorticoids (糖皮質(zhì)激素). GlucocorticoidsNatural or synthetic steroids So unbound cortisol is filtere

12、d into the urine.Dexamethasone suppression testCortisol excess secretion, will rapidly exceed the available capacity of cortisol binding globulin.The possibility that a patient may have Cushings syndrome frequently arises because they are obese（肥胖的 ）or hypertensive.ANDROGEN EXCESShyponatraemia (低鈉血癥

13、);A natural or synthetic steroid with aldosterone-like activity is called a mineralocorticoid (鹽皮質(zhì)激素).Dexamethasone suppression testleads to pathological sodium loss(病理性鈉流失) by the kidneyAdrenal insufficiency Adrenal crisisADRENOCORTICAL PATHOPHYSIOLOGYPrimary adrenocortical insufficiency17- hydroxy

14、progesterone) are secreted in large amounts.Failure of the adrenal cortex to produce cortisol and aldosterone may be due to autoimmune or infiltrative diseases(浸潤(rùn)性疾病) (infiltrative carcinoma).All of the 21-hydroxylated steroids (21-羥化類固醇) have mineralocorticoid effects to varying degrees.Glucocortic

15、oidsThey can act as anti-inflammatory(抗炎) or immunosuppressive agents(免疫抑制劑). Synthetic glucocorticoids have found therapeutic applications in a wide range of clinical situations, e.g. asthma (哮喘) and connective tissue disorders (結(jié)締組織病).So unbound cortisol is filtereADRENAL ANDROGENS腎上腺雄激素 ADRENAL A

16、NDROGENS腎上腺雄激素 The androgens (雄激素) produced by the fascicular and reticular zones of the adrenal cortex are :Androstenedione 雄烯二酮Dehydroepiandrosterone (DHA) 脫氫表雄酮DHA sulphate 脫氫表雄酮硫酸鹽. Adrenal androgens The androgens (雄激素) proALDOSTERONE醛固酮ALDOSTERONE醛固酮Aldosterone (醛固酮) is produced exclusively by

17、the zona glomerulosa (球狀帶). primarily controlled by the renin-angiotensin system (腎素血管緊張素系統(tǒng) )The metabolic pathway for the synthesis of aldosterone has many of the same enzymes involved in cortisol biosynthesis. AldosteroneAldosterone (醛固酮) is produced Other factors, including ACTH, are also involve

18、d in the regulation of aldosterone synthesis. Aldosterone is responsible for promoting sodium reabsorption and potassium excretion in the kidney.AldosteroneOther factors, including ACTH,CORTISOL皮質(zhì)醇Primary adrenocortical insufficiencyHypothalamic secretion (下丘腦分Dehydration (脫水)（繼發(fā)性腎上腺皮質(zhì)功能不全）stimulati

19、on of the adrenal cortex (刺激腎上腺皮質(zhì))by synthetic ACTH (Synacthen)ADRENAL INSUFFICIENCY腎上腺（皮質(zhì)）功能不全An initial blood sample will be taken to check the baseline level of cortisol(280-720nmol/l ).negative feedback loops (負(fù)反饋途徑).Determining the causeA prolonged excessive exposure of body tissues to cortisol

20、 or any other glucocorticoid results in Cushings syndrome(庫(kù)欣綜合征).ALDOSTERONE EXCESS2 mmol/L (hypoglycaemia)Adrenocortical insufficiency is rare but life-threatening.1mg of Dexamethasone (地塞米松 ) taken at 23:00trauma (創(chuàng)傷）Insulin-induced hypoglycaemia testNauseaA natural or synthetic steroid with aldos

21、terone-like activity is called a mineralocorticoid (鹽皮質(zhì)激素). All of the 21-hydroxylated steroids (21-羥化類固醇) have mineralocorticoid effects to varying degrees.MineralocorticoidCORTISOL皮質(zhì)醇A natural or synthCONGENITAL ADRENAL HYPERPLASIA (CAH)先天性腎上腺增生癥 CONGENITAL ADRENAL HYPERPLASIAan inherited enzyme d

22、efect in corticosteroid biosynthesis. The 21-hydroxylase (21-羥化酶) is the deficient enzyme in 95% of cases of CAH The adrenals cannot secrete cortisol. If aldosterone biosynthesis is also affected , electrolyte disturbances(電解質(zhì)紊亂) may lead to severe hyponatraemia and hyperkalaemia . It is life threat

23、ening.CAH(先天性腎上腺增生癥) an inherited enzyme defect in Because of the lack of cortisol negative feedback to the pituitary is absent ACTH secretion continues to stimulate steroid biosynthesis Cortisol precursors (皮質(zhì)醇前體) (e.g. 17- hydroxyprogesterone) are secreted in large amounts.CAH(先天性腎上腺增生癥)Because of

24、 the lack of cortisoHere, large amounts of 17- hydroxyprogesterone (17-羥孕酮)are secreted lead to virilization (男性化) in baby girl or precocious puberty(早熟性青春期) in boy CAH(先天性腎上腺增生癥)Here, large amounts of 17- hydSUMMARYSUMMARY The adrenal glands comprise three separate hormone systems: the zona glomeru

25、losa which secretes aldosterone. the zona fasciculata and reticularis which secrete cortisol and the adrenal androgens the adrenal medulla which secretes adrenaline.SUMMARY (ADRENOCORTICAL PATHOPHYSIOLOGY) The adrenal glands compriseSteroids with cortisol-like activity are known as glucocorticoids;

26、they are potent metabolic regulators and immunosuppressants.Steroids with aldosterone-like activity are called mineralocorticoids; they promote renal sodium retention.SUMMARY (ADRENOCORTICAL PATHOPHYSIOLOGY)Steroids with cortisol-like ac Adrenal steroid concentrations in serum fluctuate widely. Sing

27、le measurements are therefore of limited value in clinical investigations, and dynamic tests are widely used in diagnosis Congenital adrenal hyperplasia（先天性腎上腺增生癥） is an inherited enzyme defect in corticosteroid biosynthesis which can be fatal unless diagnosed early.SUMMARY (ADRENOCORTICAL PATHOPHYS

28、IOLOGY) Adrenal steroid concentration21-hydroxylase deficiency is the most commonly encountered form of CAH. The finding of a raised plasma 17-hydroxyprogesterone confirms the diagnosis.SUMMARY (ADRENOCORTICAL PATHOPHYSIOLOGY)21-hydroxylase deficiency is tADRENAL INSUFFICIENCY腎上腺（皮質(zhì)）功能不全 ADRENAL INS

29、UFFICIENCY腎上腺（皮質(zhì)）功Acute adrenal insufficiency (急性腎上腺功能不全) is a rare condition which if unrecognized is potentially fatal (引起死亡的). It is often relatively simple to treat once the diagnosis has been made and patients can lead a normal life. Adrenal insufficiencyAcute adrenal insufficiency (急The main c

30、linical features of Adrenal insufficiencylack of aldosteroneHyponatraemia (低鈉血癥)Hyperkalaemia (高鉀血癥)lack of cortisolLethargy(嗜睡）Anorexia（厭食）Abdominal painWeight lossPigmentation (色素沉著)The main clinical features of Adrenal crisis (腎上腺危象)Infectionoperation stress trauma (創(chuàng)傷）Adrenal insufficiency Adren

31、al crisis (life-threatening) Postural hypotension (體位性低血壓 ) Vomiting Nausea Dehydration (脫水) Adrenal crisis (腎上腺危象)Infecti腎上腺皮質(zhì)病理生理學(xué)課件Primary adrenocortical insufficiency原發(fā)性腎上腺皮質(zhì)功能不全Secondary adrenocortical insufficiency繼發(fā)性腎上腺皮質(zhì)功能不全Adrenal insufficiencyPrimary adrenocortical insuffiPrimary adrenocor

32、tical insufficiency（原發(fā)性腎上腺皮質(zhì)功能不全）Adrenal gland destruction was often due to tuberculosis (結(jié)核病) and auto-immune disease (自身免疫病).Both cortisol and aldosterone production may be affected.Adrenal insufficiencyPrimary adrenocortical insuffiSecondary adrenocortical insufficiency（繼發(fā)性腎上腺皮質(zhì)功能不全）Secondary adr

33、enal failure is frequently due to therapeutic administration of corticosteroids（皮質(zhì)類固醇）. long-standing suppression（長(zhǎng)期抑制） and the impairment（損害）of the HPA axisAdrenal insufficiencySecondary adrenocortical insufFollowing are the causes of adrenal insufficiencyFollowing are the causes of adBiochemical f

34、eatures of adrenocortical insufficiency In addition to the clinical observations, a number of biochemical results may help in the diagnosis of adrenocortical insufficiency. These are: hyponatraemia (低鈉血癥); hyperkalaemia (高鉀血癥); elevated serum urea; These are the biochemical features in many patients

35、 with Addisons Disease阿狄森氏病(primary adrenocortical insufficiency).Biochemical features of adren In primary adrenal insufficiency, patients become hyponatraemic(低鈉血癥 )for two reasons:lack of aldosterone leads to pathological sodium loss(病理性鈉流失) by the kidney contraction of the ECF (細(xì)胞外液) volumecausin

36、g hypotension and pre-renal uraemia Patients may develop life-threatening sodium depletion（鈉流失 ）and potassium retention（鉀潴留）Biochemical featuresHyponatraemic In primary adrenal inshypovolaemia（低血容量）and hypotension stimulate arginine vasopressin， AVP（精氨酸加壓素） secretioncausing water retention（水潴留）In th

37、e absence of cortisol, the kidneys ability to excrete (排泄) a water load is impaired thus leading to hyponatraemiaBiochemical featuresHyponatraemichypovolaemia（低血容量）and hypotensPigmentationLack of negative feedback of cortisol on the anterior pituitary （垂體前葉）results in an excessive secretion of ACTH.

38、 Biochemical featuresPigmentationPigmentationBiochemical featuBiochemical featuresPigmentationSince the structure of ACTH contains part of the amino acid sequence of melanocyte-stimulating hormone促黑(素細(xì)胞)激素so an excessive ACTH secretion leads to the darkening of the patients skin and mucous membranes

39、(皮膚和黏膜變黑) Pigmentation（色素沉著）Biochemical featuresPigmentatDiagnosis of adrenocortical insufficiencyIf a patient is suspected to be suffering from adrenal insufficiency, it is essential to ensure that they have an adequate sodium intake before investigations. Serum aldosterone measurements have no rol

40、e to play in the initial diagnosis of adrenal insufficiency.Diagnosis of adrenocortical in Synacthen tests Synacthen tests Synacthen is a synthetic analogue of ACTH(合成ACTH類似物) There are two kind of Synacthen teststhe short Synacthen test the depot Synacthen testSynacthen tests in the diagnosis of ad

41、renocortical insufficiency Synacthen is a synthetic analShort Synacthen test procedureAn initial blood sample will be taken to check the baseline level of cortisol(280-720nmol/l ).0.25mg Synacthen is administered intravenously (iv injection) to stimulate your own body production of cortisol. A blood

42、 sample will be taken at 30 minutes and 60 minutes after the stimulation to measure the cortisol level.Short Synacthen test procedureNormally, the resting value is within the reference range 280720nmol/l at 08:0010:00 Am. There should be an increment of more than 200nmol/L after Synacthen the final

43、value should be greater than 500 nmol/L. Diagnostic criteria of Short Synacthen test Normally, the resting value isAll criteria must be met. Failure to meet any of the criteria indicates adrenocortical inadequacy.A normal response to the Synacthen test excludes primary hypofunction. Diagnostic crite

44、ria of Short Synacthen test All criteria must be met. DiagIf a patient with an impaired response to the Synacthen test. An elevated ACTH concentration will confirm the diagnosis of primary adrenal failure in such a patient.Diagnostic criteria of Short Synacthen testIf a patient with an impaired Pati

45、ents with equivocal responses(不明確應(yīng)答) to the short Synacthen testafter stimulation of the adrenal cortex with depot Synacthen ( long-acting material長(zhǎng)效的). the short Synacthen test may be retested.The depot Synacthen testPatients with equivocal respThis depot Synacthen is given intramuscularly (IM inje

46、ction) for 3 days. On the fourth day a short Synacthen test is carried out as before.If the normal criteria for the short Synacthen test are satisfied on the second testing, it is not primary but secondary adrenocortical insufficiency.Depot Synacthen test procedureThis depot Synacthen is given an ex

47、cellent diagnostic test for adrenal insufficiencyused to check the amount of cortisol in the body and how well it can produce It also indicates the ability of adrenal cortex to respond to ACTH. Synacthen tests in the diagnosis of adrenocortical insufficiencyan excellent diagnostic test fThe HPA axis

48、 may be investigated by performing an insulin tolerance test (ITT) (胰島素耐量試驗(yàn)). ITT is used in diagnosis of pituitary insufficiency (垂體機(jī)能減退) which may lead to secondary failure of the adrenal cortex.Diagnosis of adrenocortical insufficiencyThe HPA axis may be investigatSUMMARY(Adrenal insufficiency) A

49、drenocortical insufficiency is rare but life-threatening. Failure of the adrenal cortex to produce cortisol and aldosterone may be due to autoimmune or infiltrative diseases(浸潤(rùn)性疾病) (infiltrative carcinoma).SUMMARY(Adrenal insufficiency The Synacthen test is used in diagnosis of primary adrenocortica

50、l failure. The insulin tolerance test is used in diagnosis of pituitary insufficiency which may lead to secondary failure of the adrenal cortex.SUMMARY(Adrenal insufficiency) The Synacthen test is used inHYPERFUNCTION OF THE ADRENAL CORTEX腎上腺皮質(zhì)功能亢進(jìn)HYPERFUNCTION OF THE ADRENAL C Hyperfunction of the

51、adrenal cortex can be conveniently discussed in terms of the overproduction of the three main products:Cortisol (皮質(zhì)醇)Adrenal androgens (腎上腺雄激素) Aldosterone (醛固酮) Hyperfunction of the adrenal cortex Hyperfunction of the adCORTISOL EXCESSCORTISOL EXCESSA prolonged excessive exposure of body tissues to

52、 cortisol or any other glucocorticoid results in Cushings syndrome(庫(kù)欣綜合征).It is one of the most difficult endocrine diagnoses to make. Cortisol excessA prolonged excessive exposureThe main clinical features of Cushings syndromeDisorders of lipid metabolismDisorders of protein metabolism Disorders of

53、 glycometabolism Electrolyte disturbances HypertensionBreakdown of immune function sexual disturbance The main clinical features of 腎上腺皮質(zhì)病理生理學(xué)課件 In any investigation of Cushings syndrome the clinician should ask two questions:Does the patient actually have Cushings syndrome? The possibility that a p

54、atient may have Cushings syndrome frequently arises because they are obese（肥胖的 ）or hypertensive. Cortisol excess In any investigation ofOnce the diagnosis of Cushings syndrome is established, then a second question may be asked:What is the cause of the excess cortical secretion?Cortisol excessOnce t

55、he diagnosis of CushinDiagnosis of Cortisol excess（1）Iatrogenic（醫(yī)源性） Cushings syndrome should be diagnosed from the patient history and clinical examination (the steroid may have been taken)Cortisol excess secretion, will rapidly exceed the available capacity of cortisol binding globulin. Diagnosis

56、of Cortisol excess（1So unbound cortisol is filtered into the urine.Urinary free cortisol(尿游離皮質(zhì)醇) in a 24h collectionor assessed as a cortisol / creatinine ratio(皮質(zhì)醇/肌酐) in an early morning urine sampleIt is the initial screening test in a patient suspected of adrenocortical hyperfunction. Diagnosis

57、of Cortisol excess（2）So unbound cortisol is filteRepeatedly high early morning urine cortisol / creatinine ratios are evidence enough to proceed with further investigations of the patient. If the test is negative on three occasions, Cushings syndrome may be excluded from the differential diagnosis.D

58、iagnostic criteriaRepeatedly high early morning Disappearance of circadian rhythm Cortisol concentrations measured at 08:00 and 22:00 normally show a circadian rhythm（晝夜節(jié)律） the evening sample having a lower value than that in the morning. This difference is usually not apparent in the patient with C

59、ushings syndrome. Diagnosis of Cortisol excess（3） Disappearance of circadian rhDexamethasone suppression test地塞米松抑制試驗(yàn)Insulin-induced hypoglycaemia testDiagnosis of Cortisol excess（4）Dexamethasone suppression testDexamethasone suppression test1mg of Dexamethasone (地塞米松 ) taken at 23:00 to suppress th

60、e serum cortisol level at 08:00 the following morningor to suppress the urinary cortisol secretion overnight (as measured by an early morning urine cortisol / creatinine ratio)Dexamethasone suppression testIf failure to the suppression of dexamethasoneIt is another indicator of Cushings syndrome.Dex