Download - Kidney Lecture 2 Non-immune Glomerular Disease, Systemic Diseases, Infections, Vascular Diseases
Kidney Lecture 2Kidney Lecture 2
Non-immune Glomerular Non-immune Glomerular Disease, Systemic Diseases, Disease, Systemic Diseases, Infections, Vascular DiseasesInfections, Vascular Diseases
Learning ObjectivesLearning Objectives
Describe the clinical and pathologic features of:Describe the clinical and pathologic features of:– Minimal Change NephropathyMinimal Change Nephropathy– Focal Segmental GlomerulosclerosisFocal Segmental Glomerulosclerosis– Chronic GlomerulonephritisChronic Glomerulonephritis– Lupus ErythematosisLupus Erythematosis– Diabetes MellitusDiabetes Mellitus– AmyloidosisAmyloidosis– PyelonephritisPyelonephritis– Drug-Induced Acute Interstitial NephritisDrug-Induced Acute Interstitial Nephritis– Hypertensive NephropathyHypertensive Nephropathy– Thrombotic MicroangiopathyThrombotic Microangiopathy
Non-Immune GlomerulopathiesNon-Immune Glomerulopathies
Minimal Change NephropathyMinimal Change Nephropathy
Focal Segmental Glomerular SclerosisFocal Segmental Glomerular Sclerosis– IdiopathicIdiopathic– HIV NephropathyHIV Nephropathy
Hereditary NephritisHereditary Nephritis– AlportAlport– Thin Basement MembraneThin Basement Membrane
Chronic GlomerulonephritisChronic Glomerulonephritis
Minimal Change NephropathyMinimal Change Nephropathy
AKA Nil Disease, Lipoid NephrosisAKA Nil Disease, Lipoid Nephrosis
No abnormalities by light, IFNo abnormalities by light, IF
Fusion of foot processes by EMFusion of foot processes by EM– AKA foot process effacementAKA foot process effacement
Usually children 2 – 6Usually children 2 – 6
Nephrotic syndromeNephrotic syndrome
Responds to steroidsResponds to steroids
Minimal Change Disease – Epithelial Minimal Change Disease – Epithelial Cell Foot Process EffacementCell Foot Process Effacement
FOCAL SEGMENTAL FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)GLOMERULOSCLEROSIS (FSGS)
Clinical - proteinuria, often nephrotic syndromeClinical - proteinuria, often nephrotic syndrome
Primary: Idiopathic FSGS Primary: Idiopathic FSGS
- pathogeneis unknown possibly apolipoprotein L1 (ApoL1) - pathogeneis unknown possibly apolipoprotein L1 (ApoL1) mutation - related to trypanosome resistancemutation - related to trypanosome resistance
Primary: Heredetary FSGS - rarePrimary: Heredetary FSGS - rare
- pathogeneis due to nephrin, podocin, - pathogeneis due to nephrin, podocin, -actinin 4 mutation -actinin 4 mutation
Secondary – most common: Secondary – most common: - HIV- HIV
- Heroin nephropathy- Heroin nephropathy
- Adaptive response to lack of renal tissue (Compensatory)- Adaptive response to lack of renal tissue (Compensatory)
- Obesity related glomerulopathy- Obesity related glomerulopathy
Variable steroid response, tends to progress to renal failure Variable steroid response, tends to progress to renal failure
Focal Segmental Focal Segmental GlomerulosclerosisGlomerulosclerosis
HIV NephropathyHIV Nephropathy
Chronic GlomerulonephritisChronic Glomerulonephritis
Common cause of chronic renal failureCommon cause of chronic renal failureMay follow any other glomerulonephritis but May follow any other glomerulonephritis but frequently insidious without prior historyfrequently insidious without prior historySmall granular kidneysSmall granular kidneysWidespread glomerular scarring +/– cluesWidespread glomerular scarring +/– clues
Chronic GlomerulonephritisChronic Glomerulonephritis
Chronic GlomerulonephritisChronic Glomerulonephritis
Systemic DiseaseSystemic Disease
Lupus ErythematosisLupus Erythematosis
Diabetes MellitusDiabetes Mellitus
AmyloidosisAmyloidosis
Lupus Nephritis – WHO ClassificationLupus Nephritis – WHO Classification
Class I – Minimal or no alterationClass I – Minimal or no alterationClass II – Mesangial ProliferationClass II – Mesangial Proliferation– Mildly increased mesangium, mesangial deposits by IF, EMMildly increased mesangium, mesangial deposits by IF, EM
Class III – Focal Proliferative GNClass III – Focal Proliferative GN– Segmental proliferation, fibrinoid, in < 50% of glomeruliSegmental proliferation, fibrinoid, in < 50% of glomeruli– Hematuria, proteinuria, subendothelial deposits, capillary Hematuria, proteinuria, subendothelial deposits, capillary
and mesangial deposits of many types of Ig, complementand mesangial deposits of many types of Ig, complement
Class IV – Diffuse Proliferative GNClass IV – Diffuse Proliferative GN– More severe clinically than Class III, including nephrotic More severe clinically than Class III, including nephrotic
syndrome and renal insufficiencysyndrome and renal insufficiency– >50% glomerular involvement, “wire loops”, morphologic, IF >50% glomerular involvement, “wire loops”, morphologic, IF
and EM changes more pronouncedand EM changes more pronounced
Class V – Membranous GlomerulonephritisClass V – Membranous Glomerulonephritis– Morphologically identical to idiopathic membranousMorphologically identical to idiopathic membranous
Lupus Nephritis WHO Class IVLupus Nephritis WHO Class IV
Lupus – Subendothelial DepositsLupus – Subendothelial Deposits
Lupus- Endothelial Tubuloreticular BodiesLupus- Endothelial Tubuloreticular Bodies
Activity IndexActivity Index
Indication of level of inflammationIndication of level of inflammation– CresentsCresents– Glomerular inflammationGlomerular inflammation– Necrosis and karyorrhexisNecrosis and karyorrhexis– Interstitial inflammationInterstitial inflammation– Wire loopsWire loops– Endocapillary proliferationEndocapillary proliferation
Worse prognosis for higher scoreWorse prognosis for higher score
Chronicity IndexChronicity Index
Indication of irreversible damageIndication of irreversible damage– Interstitial fibrosisInterstitial fibrosis– Glomerular sclerosisGlomerular sclerosis– Fibrous CrescentsFibrous Crescents– Tubular atrophyTubular atrophy
Worse prognosis for higher scoreWorse prognosis for higher score
Question 1Question 1
A patient with lupus erythematosis has basement membrane spikes on histology and subepithelial deposits by electron microscopy, the WHO classification is which of the following:– Class I– Class II– Class III– Class IV– Class V
Question 1Question 1
A patient with lupus erythematosis has basement membrane spikes on histology and subepithelial deposits by electron microscopy, the WHO classification is which of the following:– Class I– Class II– Class III– Class IV– Class V
Kidney Lesions in DiabetesKidney Lesions in DiabetesEnd stage renal disease in up to 40%End stage renal disease in up to 40%Glomerular lesionsGlomerular lesions– Diffuse mesangial sclerosisDiffuse mesangial sclerosis– Nodular (Kimmelstiel-Wilson) glomerulosclerosisNodular (Kimmelstiel-Wilson) glomerulosclerosis– Capillary basement membrane thickeningCapillary basement membrane thickening– Exudative lesionsExudative lesions
Hyalinizing arteriolosclerosisHyalinizing arteriolosclerosisPapillary necrosisPapillary necrosisMechanismsMechanisms– Metabolic defectMetabolic defect– Non-enzymatic protein glycosylationNon-enzymatic protein glycosylation– Hemodynamic effectsHemodynamic effects
Kimmelsteil-Wilson NoduleKimmelsteil-Wilson Nodule
Question 2Question 2
The abnormality commonly seen in diabetic nephropathy by light microscopy is referred to as– Crescent– Spikes– Kimmelsteil-Wilson nodules– Fenestrated endothelium
Question 2Question 2
The abnormality commonly seen in diabetic nephropathy by light microscopy is referred to as– Crescent– Spikes– Kimmelsteil-Wilson nodules– Fenestrated endothelium
Papillary NecrosisPapillary Necrosis
Other Systemic Diseases Other Systemic Diseases Affecting GlomeruliAffecting Glomeruli
AmyloidosisAmyloidosis– Inflammatory – Amyloid AAInflammatory – Amyloid AA– Plasma Cell Dyscrasias – Amyloid ALPlasma Cell Dyscrasias – Amyloid AL– HeredetaryHeredetary
Bacterial EndocarditisBacterial Endocarditis
Essential Mixed CryoglobulinemiaEssential Mixed Cryoglobulinemia
AmyloidosisAmyloidosis
Congo RedCongo Red
IgG ImmunofluorescenceIgG Immunofluorescence
Infectious and Inflammatory Infectious and Inflammatory Tubulointerstitial DiseasesTubulointerstitial Diseases
PyelonephritisPyelonephritis– AcuteAcute– ChronicChronic– Reflux NephropathyReflux Nephropathy
Viral InfectionViral Infection
Acute Interstitial NephritisAcute Interstitial Nephritis
PyelonephritisPyelonephritis
PathogenesisPathogenesis– Gram neg– E. coli, Proteus, Klebsiella, etcGram neg– E. coli, Proteus, Klebsiella, etc– Hematogenous infection –sepsis, obstructionHematogenous infection –sepsis, obstruction– Ascending infection -Ascending infection -
AcuteAcute
ChronicChronic– Reflux NephropathyReflux Nephropathy– Chronic Obstructive PyelonephritisChronic Obstructive Pyelonephritis
Figure 20-35 Schematic representation of pathways
of renal infection. Hematogenous infection results from bacteremic
spread. More common is ascending infection, which results from a combination of urinary bladder infection, vesicoureteral reflux, and
intrarenal reflux.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease
© 2005 Elsevier
Acute Pyelonephritis- Acute Pyelonephritis- AscendingAscending
Acute Pyelonephritis -Acute Pyelonephritis -HematogenousHematogenous
Acute PyelonephritisAcute Pyelonephritis
Bacteria in TubulesBacteria in TubulesH and E GramH and E Gram
UrineUrine
Polyoma VirusPolyoma Virus
Polyoma Virus ImmunoperoxidasePolyoma Virus Immunoperoxidase
Chronic PyelonephritisChronic Pyelonephritis
Chronic PyelonephritisChronic Pyelonephritis
Chronic PyelonephritisChronic Pyelonephritis
Chronic PyelonephritisChronic PyelonephritisPredisposing factorsPredisposing factors
Progression of acute pyelonephritisProgression of acute pyelonephritis
Chronic obstructionChronic obstruction
Reflux nephropathyReflux nephropathy
Reflux NephropathyReflux Nephropathy
Drug-Induced NephritisDrug-Induced Nephritis
Tubulointerstitial NephritisTubulointerstitial Nephritis– Sulfonamides, synthetic penicillins and other Sulfonamides, synthetic penicillins and other
antibioticsantibiotics– Diuretics, NSAIDS, Misc Drugs (Allupurinol, Diuretics, NSAIDS, Misc Drugs (Allupurinol,
Cymetidine)Cymetidine)
Fever, eosinophilia, rash, renal Fever, eosinophilia, rash, renal abnormalitiesabnormalities– Rising creatinine, hematuria, leukocyturiaRising creatinine, hematuria, leukocyturia
Analgesic NephropathyAnalgesic Nephropathy– Papillary NecrosisPapillary Necrosis
Drug-Induced Drug-Induced Acute Interstitial NephritisAcute Interstitial Nephritis
Vascular DiseasesVascular Diseases
Hypertensive NephropathyHypertensive Nephropathy– EssentialEssential– MalignantMalignant– Renal Artery StenosisRenal Artery Stenosis
Thrombotic MicroangiopathyThrombotic Microangiopathy
ArteriosclerosisArteriosclerosis
Renal InfarctRenal Infarct
Scleroderma renal crisisScleroderma renal crisis
PreeclampsiaPreeclampsia
Hypertensive NephropathyHypertensive Nephropathy
Benign NephrosclerosisBenign Nephrosclerosis
Malignant HypertensionMalignant Hypertension– Hyperplastic arteriolitisHyperplastic arteriolitis– Fibrinoid necrosis of afferent arterioleFibrinoid necrosis of afferent arteriole
Renal Artery StenosisRenal Artery Stenosis– Increased renin secretion, conversion of Increased renin secretion, conversion of
angiotensinogenangiotensinogen
Benign NephrosclerosisBenign Nephrosclerosis
Arteriolar HyalinizationArteriolar Hyalinization
Hyperplastic ArteriolitisHyperplastic Arteriolitis
Malignant HypertensionMalignant Hypertension
Fibrinoid Necrosis of Afferent ArterioleFibrinoid Necrosis of Afferent Arteriole
Thrombotic MicroangiopathyThrombotic Microangiopathy
Hemolytic Uremic Syndrome (HUS)Hemolytic Uremic Syndrome (HUS)– Childhood – verocytoxin – uncooked meatChildhood – verocytoxin – uncooked meat– GI bleeding, oliguria, hematuria, hemolytic anemiaGI bleeding, oliguria, hematuria, hemolytic anemia– Adult –infection, SLE, pregnancy, immunosuppressionAdult –infection, SLE, pregnancy, immunosuppression– Familial Familial
Thrombotic Thrombocytopenic Purpura (TTP)Thrombotic Thrombocytopenic Purpura (TTP)– Usually adult Usually adult – CNS changes, hemolytic anemia, thrombocytopeniaCNS changes, hemolytic anemia, thrombocytopenia
PathogenesisPathogenesis– Endothelial injuryEndothelial injury– Platelet aggregationPlatelet aggregation– Vascular obstruction and vasoconstrictionVascular obstruction and vasoconstriction– Distal ischemiaDistal ischemia
Hemolytic Uremic SyndromeHemolytic Uremic Syndrome
Atherosclerotic Ischemic Renal DiseaseAtherosclerotic Ischemic Renal Disease
Renal InfarctRenal Infarct