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What Every

M e d i c a l

Student Needsto Know About . . .

What Every

M e d i c a l

Student Needsto Know About . . .

Roger S. Riley, M.D., Ph.D.November, 2001

rsriley@hsc.vcu.edu

http://www.pathlabonline.com

Renal

Pa tho logy

Renal

Pa tho logy

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Course ContentsCourse Contents

s Anatomy/physiology review

s Glomerular diseases

s Tubulointerstitial diseasess Vascular diseases

s Urinary tract infections

s Obstructive diseases

s Congenital anomalies

s Neoplastic diseases

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Anatomy ReviewAnatomy Review

Bladder

Ureters

Kidneys

Renal FunctionRenal Function

s Remove wastes

s Maintain hemostasis

s Secrete EPO

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Rena l Ana t om yRena l Ana tom y

Renal column

(of Bertin)

Minor calyx

Papilla

Renal column

(of Bertin)

Cortex

Renal

Pelvis

Medullary

pyramid

Majorcalyx

Minor calyx

Papilla

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A na t o m y o f t he

N e p h r o n

A na t o m y o f t he

N e p h r o n

Afferent arteriole

Proximal convoluted tubule

Glomerulus

Efferent arteriole

Distal convoluted

tubule

Collecting

duct

Bowmans capsule

Loop of Henle

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A n a t o m y o f t h e G lo m e r u lu sA n a t o m y o f t h e G lo m e r u lu s

Glomerular capsule

Capillary lumen

Mesangial cell

GBM

Mesangial matrix

Endothelial cell

Visceral epithelial cell

Parietal epithelial cell

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G lo m e r u la r An a t o m yG lo m e r u la r An a t o m y

Capillary Lumen

Endothelial cell

Glomerular

basement

membrane

Epithelial

cell

Podocytes

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Classi f icat ion of Glomerular DiseaseClassi f icat ion of Glomerular Disease

EtiologyEtiology

PathologyPathology

Clinical

Features

Clinical

Features

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Nephr i t ic SyndromeNephr i t ic Syndrome

s Acute, rapidly progressive, or chronic

s Manifestations

Hematuria

Variable proteinuria

Impaired renal function

Hypertension

Edema

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Nephrot ic SyndromeNephrot ic Syndrome

s Insidious onset

s Manifestations

Proteinuria

Hypoalbuminemia

Edema

Hyperlipidemia

Lipiduria

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Pr im a ry G lom eru la r D isea sesPr im a ry G lom eru la r D isea ses

s Nephrotic presentationMinimal change disease

Focal segmental glomerulosclerosis

Membranous glomerulonephritis

Membranoproliferative glomerulonephritis

s Acute nephritis

Acute proliferative glomerulonephritis

Crescentic glomerulonephritis

Anti-GBM Disease

s Primary hematuria

IgA Nephropathy

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Freq ue ncy o f G lom eru la r D isea sesFreq ue ncy o f G lom eru la r D isea ses

Lupusnep

hr

itis

FSGS

IgA

Nep

hropa

thy

Mem

branous

Diabe

tic

Po

lyar

ter

itis

Crescen

tic

MPGN

My

eloma

Nep

hropa

thy

MCGN

HIVNep

hropa

thy

Here

ditary

Acu

tePro

lifera

tive

Amy

loidos

is

Other

0

20

40

60

80

100

Presbypterian-University Hospital

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Et io log y o f G lom er u la r D isea seEt io log y o f G lom eru la r D isea se

Disruption of GBM

Injury to glomerular

epithelial cells

Neutralization of GBM

negative charge

Hydrodynamic factors

Proteinuria Hematuria Decreased GFR

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What causes

glomerular disease ?

Most are of immunologic

origin, and caused by

immune complexes !

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Et io lo g y o f

Glomeru lar D isease

Et io lo g y o f

Glomeru lar D isease

Idiopathicor Other Mechanism Anti-GBM Ab

GBM Immune

Complexes

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Glomerular Response to In jury

Ant i -GBM Disease

Glomerular Response to In jury

Ant i -GBM Disease

Mesangium

Anti-GBM

Chemotaxis

CC3a

Epithelium

GBM

Endothelium

PMN

Fibrin Crescent

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Glom er u la r Resp on se t o In ju ry

Im m un e Com p lex D isea se

Glom eru la r Resp on se t o In ju ry

Im m un e Com p lex D isea se

Immunecomplexes

Protein loss

Chemotaxis

Epithelium

GBM

Endothelium

DepositsMesangialdeposits

Deposits

C

C3a

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How are renal diseases

diagnosed ?

Usually by history, physical

findings, Urinalysis and other

laboratory data. Occasionally a

renal biopsy must be

performed !

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Renal Biopsy ProcessingRenal Biopsy Processing

LightMicroscopy

H&E stain

PAS stain

Silver stain

Trichrome stain

Fluorescence

Microscopy

IgG, IgA, IgM

C3, C4, C1q

Fibrinogen

Kappa, Lambda

ElectronMicroscopy

Liquid N2

Frozen

Sections

Fixative

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?

There is a diffuse proliferative

glomerulonephritis with mesangial

and subendothelial deposits and

acute interstitial nephritis !

Gl l I jG l m l I j

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Glomeru la r In ju ry

Dif f u se vs. Fo ca l

Glomeru la r In ju ry

Dif f u se vs. Fo ca l

XX

XX XX

XX

XX

XXXX

XX

XXXX

XX

XX

Diffuse DiseaseDiffuse Disease Focal DiseaseFocal Disease

Gl l I jG lomeru la r In ju ry

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Glomeru la r In ju ry

G lob a l vs. Seg m en ta l

G lomeru la r In ju ry

G lob a l vs. Seg m en ta l

XX

XX

XXXX

XX

XX

XX

Global DiseaseGlobal Disease

Segmental DiseaseSegmental Disease

I C lImmune Complexes

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Immune Complexes

Subep i the l ia l

Immune Complexes

Subep i the l ia l

Epithelial Cell

Capillary Lumen

I C l

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Immune Complexes

Subendo the l i a l

Immune Complexes

Subendo the l i a l

Epithelial Cell

Capillary Lumen