医学精品课件：2014 中德班尿崩症.ppt

1、Tongji HospitalHushuhong2014.9.Diabetes insipidus DI Physiology of urine concentration and dilutionAdenohypophsis(anterior pituitary)ACTH,Gonadotropin (FSH,LH),Prolactin,GH,TSH Neurohypophysis(posterior pituitary):antidiuretic hormone(ADH)oxytocin ADH also known as arginine vasopressin(AVP)in human

2、and other mammals The actions of ADHThe actions of ADH are mediated through V2 receptors by altering the water permeability of the cortical and medullary collecting tubules(CCD and MCD).Concentration of urine CCDMCDUrine Osmolality:Without ADHMin:Urine Osm=50 mOsmWith ADHMax :Urine Osm=1200 mOsm Reg

3、ulator of ADH1.Effective extracellular fliud(ECF)osmolality changes sensed by osmoreceptors in supraoptic and periventricular nuclei (in hypothalamus)2.Effective ECF volume sensed by baroreceptors in aortic arch,carotid sinus,left atrium.Other ADH stimulantsEmotional factors and stressSleepMedcines:

4、chlorpropamide clofibrate opiates nicotine phenobarbitoneDiabetes insipidus(DIDI)Diabetes insipidusDiabetes insipidus(DIDI)is a condition characterized by:Excretion of large amounts of severely diluted urine(polyuria)andExcessive fluid intake (polydipsia)Caused by:1.a deficiency of ADHcentral diabet

5、es insipidus(CDI)or 2.an insensitivity of the kidneys to ADHnephrogenic diabetes insipidus(NDI)*Diabetes:pass through*Insipidus:without tasteCauses of CDI1.SecondaryNeurosurgeryNeurotrauma Suprasellar tumors Infiltrative diseases (histiocytosis X,sarcoidosis)Hypoxic or ischemic Radiation Infection(m

6、eningitis or encephalitis)vascular lesions2.Idiopathic Autoimmune:destruction of the ADH hormone-secreting cells,characterized by lymphocytic inflammation of the pituitary stalk and posterior pituitary Normal pituitary gland:Sagittal T1-weighted image shows normal appearing pituitary gland with post

7、erior pituitary bright spot(arrow)T1-weighted MR images showing a small pituitary gland with absent bright spot of the neurohypophysis(arrow)and thickened pituitary stalk in 18-years-old man with sudden onset of polyuria and polydipsia 3.Genetic Usually an autosomal dominant disease caused by mutati

8、ons involving AVP gene.Causes of NDI1.Primary(familial)X-linked recessive genetic defect of the V2V2 receptor gene.A rare autosomal recessive or dominant pattern of mutation in the aqua-porin gene AQP2AQP2 2.Secondary chronic pyelonephritis/tubulointerstitial disease/CRF/obstructive uropathy/polycys

9、tic diseaseDrugs(lithium,colchcine,fluoride,demeclocycline)hypercalcemiahypokalemiaProtein deprivationAmylodosisSjoegren syndromeClinical featuresPolyuria(including Polyuria(including nocturianocturia)urine volum:4L/day urine SG:1.005 urine osmolality 50-200 mOsm/kg(300 mOsm/kg)PolydipsiaPolydipsia

10、predilection for drinking cold liquidsSymptoms of underlying causeSymptoms of underlying causeComplications:Complications:*Body weight reduction*Obstipation*Hypernatremic dehydration and its neurologic sequelea*Growth retardation(children)*HydronephrosisDiagnostic workupIn a normal well hydrated sub

11、ject with intact function of ADH,the random plasma osmolality is 290mOsm/L and urine osmolality is 300-450mOsm/LIn a patient with DI and free excess to water,plasma osmolality is 290mOsm/L and urine osmolality is 50-200mOsm/LSmultaneous measurement of plasma and urine osmolality establish the diagno

12、sis in most severe DI2012.9.27A male outpatient presented with polydipsia and polyuriasmultaneous measurement of urine osmolality=687mOsm/kg.H2O plasma osmolality=304mOsm/kg.H2OExclusion of DIwater deprivation test-When?Water deprivation test is needed(1)for patients with partial ADH deficiency(2)to

13、 differentiate DI from primary polydipsia water deprivation test-how?Be done in the morning under observationWeigh the patient and measure plasma and urine osmolality every 2 hours,4-18 hours deprivation is enough.water deprivation test-when endend?The test should be ended once one of the following

14、occurs:(1)The urine osmolality reaches a normal value of above 600 mOsm/kg(2)The urine osmolality is stable on 2 or 3 successive measurements(difference30mOsm/L,indicating a Plateua phase)(3)Syndrome and sign of dehydration*At the end of test,exogenous ADH is administered(ADH 5Uor DDAVP 2 ug sc;or 2

15、0 ug DDAVP nasally).Urine osmolality is then measured hourly for the next 2 hours(q1hr).water deprivation test-InterpretationNormal subjects or primary polydipsiaNormal subjects or primary polydipsia After water deprivation:the urine output is reduced Urine osmolality rises 600-1200 mOsm/kgplasma os

16、molality hardly rises(300 mOsm/kg),urine/plasma osmolality ratio rises2.0 After exogenous ADH:Urine osms increase minimally(5-10%)DI patientsDI patientsAfter water deprivation:*The plasma but not the urine osmolality rises*U/P osmolality ratio remains 1.5:1.0 complete CDI 1.0-1.5 partial CDI After e

17、xogenous ADHCDI:urine osms increase *over 50-100%in complete CDI *over 10-50%in partial CDI.NDI:urine osms increase by less than 5-10%.water deprivation test results of normnal,CDI and NDI subjectswater deprivation test-Case 1female，49 yr。ID:977049polydipsia，polyuria for 2m，but no nuctouriaPhysical

18、examination:normalOGTT and thyroid function test:normaltimeUrine SGU-sms(mOsm/L)P-osms(mOsm/L)UrinevolumeBw(kg)BP(mmHg)HR/min10pm1.02050912052.5101/63706am1.02061815051.5100/62668am1.01568110051.5104/676610am1.0156024051.1108/696911am7222711051.5104/686912N*ADH 5u sq705 1051.56913:20651?饮水？279 10251

19、.5102/6869U/P=2.66diagnosis：normal or primary polydipsia010020030040050060070080010pm6am8am10am11am12N2pmU-OsmP-OsmADH 5u sqU/P=2.66diagnosis：normal or primary polydipsiawater deprivation test-Case 2male，aged 36 yPolydipsia for 6m。Urine volume7000-8000ml/d，polyuria despite of no drinking,nuctouria.w

20、ater deprivation test-resulttimeU-osms(mOsm/LP-osms(mOsm/L6am668am9410am12128510:30*ADH 5u sq11:3053312:30551U/P=0.42diagnosis:complete CDI(551-121)/121=355%water deprivation test-result01002003004005006006am8am10am11am12NU-OsmP-OsmADH 5u sqU/P=0.42diagnosis:complete CDI(551-121)/121=355%water depri

21、vation test-Case 3male,27 yPolydipsia and polyuria for 1y。Urine volume 6000ml/d,no headache and visiual disordersPE：normaltimeU-(ml)U-SGU-mOsmBw(Kg)（reduction%）BP-mmHg1:256001.0109867118/803:38 4501.0121246.18 6101.0101358.08 4001.01218364.5(3.73%)119/7610:40 3501.01223254(4.47%)127/80timeU-(ml)U-SG

22、U-mOsmBw(Kg)（reduction%）BP-mmHg12:40 3501.01019814:15 3001.01026563.5(5.22%)124/9015:30 1501.014308113/8816.171001.01436217:00*(ADH)1001.01637863(4.62%)132/87 18:301101.02254119:301001.02257164(4.47%)116/92 Diagnose:partiale CDI(571-378)/378=51%01002003004005006001:253:386.188.0810:4012:4014:1515:30

23、16.1717:00*18:3019:30U-Osm(ADH)Diagnose:partiale CDI(571-378)/378=51%MRI of Case 3Pituitary MRI in T1-weighted images showed (1)loss of the hyperintense signal of the posterior pituitary (2)thenckening of the pituitary stalk Cause may be lymphocytic infundibulo-neurohypophysitis*Treatment:with DDAVP

24、(Minirin)100mg Bid,urine volume reduced to 2100ml/24hr.Treatment of DI DesmopressinDesmopressintwo-amino acid of ADH are substituted potent antidiuretic activity but no vasopressor activity safe during pregnancy for both the mother and the fetusRisks:Water retention and the development of hyponatremia.Thiazide Thiazide diureticsdiureticsAct independent of ADH.via a hypovolemia-induced increase in sodium and water reabsorption in the proximal tubule Follow up1.Urin volume and medication dosis2.Sellar and pituitary MRI pro 1-2 yr Thanks!