Diabeticmicroangiopathy.Oneofthemostconsistentmorphologicfeaturesofdiabetesisdiffusethickeningofbasementmembranes.Thethickeningismostevidentinthecapillariesoftheskin,skeletalmuscle,retina,renalglomeruli,andrenalmedulla.However,italsomaybeseeninnonvascularstructuressuchasrenaltubules,theBowmancapsule,peripheralnerves,andplacenta.Bybothlightandelectronmicroscopy,thebasallaminaseparatingparenchymalorendothelialcellsfromthesurroundingtissueismarkedlythickenedbyconcentriclayersofhyalinematerialcomposedpredominantlyoftypeIVcollagen(
Fig.20.28 ).Ofnote,despitetheincreaseinthethicknessofbasementmembranes,diabeticcapillariesareleaky,leadingtoextravasationofplasmaproteins.Themicroangiopathyunderliesthedevelopmentofdiabeticnephropathy,retinopathy,andsomeformsofneuropathy.Anindistinguishablemicroangiopathycanbefoundinagednondiabeticpatients,butrarelytotheextentseeninindividualswithlong-standingdiabetes.
Diabeticnephropathy.Thekidneysareprimetargetsofdiabetes(seealsoChapter14).Renalfailureissecondonlytomyocardialinfarctionasacauseofdeathfromthisdisease.Thelesionsincludemainly:(1)glomerularlesions;(2)renalvascularlesions,principallyarteriolosclerosis;and(3)pyelonephritis,includingnecrotizingpapillitis.
Themostimportantglomerularlesionsarecapillarybasementmembranethickening,diffusemesangialsclerosis,andnodularglomerulosclerosis.Theglomerularcapillarybasementmembranesarethickenedalongtheirentirelength.Thischangecanbedetectedbyelectronmicroscopywithinafewyearsoftheonsetofdiabetes,sometimeswithoutanyassociatedchangeinrenalfunction(
Fig.20.29
Fig.20.27Severerenalhyalinearteriolosclerosisinaperiodicacid–Schiffstainedspecimen.Notethemarkedlythickened,tortuousafferentarteriole.Theamorphousnatureofthethickenedvascularwallisevident.(Courtesy of Dr. M.A. Venkatachalam, Department of Pathology, University of Texas Health Science Center, San Antonio,Texas.) http://ebooksmedicine.net
Fig.20.28Renalcortexshowingthickeningoftubularbasementmembranesinaspecimenfromadiabeticpatient.(Periodicacid–Schiffstain.)
Diffusemesangialsclerosisreferstoanincreaseinmesangialmatrixassociatedwithmesangialcellproliferationandbasementmembranethickening.Itisfoundinmostindividualswithdiseaseofmorethan10years’duration.Whenglomerulosclerosisissevere,patientsdevelopthenephroticsyndrome,characterizedbyproteinuria,hypoalbuminemia,andedema(Chapter14).
Fig.20.30 ).ThesenodulesarePAS-positiveandusuallycontaintrappedmesangialcells.Nodularglomerulosclerosisisencounteredinapproximately15%to30%ofindividualswithlong-termdiabetesandisamajorcontributortorenaldysfunction.Diffuse
Fig.20.29Renalglomerulusshowingmarkedlythickenedglomerularbase-mentmembrane(B) inadiabetic.L,Glomerularcapillarylumen;U,urinaryspace.(Courtesy of Dr. Michael Kashgarian, Department of Pathology,Yale Univer-sity School of Medicine, New Haven, Connecticut.)