Pathology of Kidney Pathology of Kidney Part IIPart II

Dr. Sachin Kale, MD.Dr. Sachin Kale, MD.

Asso. Professor, Dept of Asso. Professor, Dept of Pathology.Pathology.

Nephrotic syndromeNephrotic syndrome

Massive proteinuria (>3.5 gm/24 Massive proteinuria (>3.5 gm/24 hrs)hrs)

HypoalbuminemiaHypoalbuminemia Generalised edemaGeneralised edema HyperlipidemiaHyperlipidemia Why? – derangement in glomerular Why? – derangement in glomerular

capillary wall – Increased capillary wall – Increased permeabilitypermeability

NS: pathophysiologyNS: pathophysiology

Proteinuria –depletion of serum Proteinuria –depletion of serum albuminalbumin

Edema – results from loss of colloid Edema – results from loss of colloid pressure of blood – accumulation pressure of blood – accumulation of fluid in interstitial tissueof fluid in interstitial tissue

Sodium/ HSodium/ H22O retention –O retention – Aldosterone, ADH, decreased ANPAldosterone, ADH, decreased ANP Edema: soft and pitting – Edema: soft and pitting –

periorbital regionperiorbital region

Largest proportion of protein lost Largest proportion of protein lost is albuminis albumin

Highly selective proteinuria – low Highly selective proteinuria – low molecular wt proteinsmolecular wt proteins

Poorly selective proteinuria : Poorly selective proteinuria : HMW in addition to albuminHMW in addition to albumin

NS: pathophysiologyNS: pathophysiology

Genesis of Genesis of HyperlipidemiaHyperlipidemia Increased levels of Increased levels of

Cholesterol, TG, Cholesterol, TG, VLDL, LDL, LP(a), VLDL, LDL, LP(a), apolipoproteinsapolipoproteins

Increased synthesis Increased synthesis of Lipoproteins in of Lipoproteins in liver, abnormal liver, abnormal transport of lipids, transport of lipids, decreased decreased catabolism.catabolism.

Lipiduria: Lipiduria: lipoproteins leak lipoproteins leak across glomerular across glomerular capillary wall.capillary wall.

Oval fat bodiesOval fat bodies

Vulnerability towards infectionVulnerability towards infection Staph, peumococci, why? Loss of Staph, peumococci, why? Loss of

Immunoglobulins, LMW Immunoglobulins, LMW complementcomplement

Thrombotic/thomboembolic Thrombotic/thomboembolic complications – loss of complications – loss of anticoagulant factorsanticoagulant factors

Renal vein thrombosisRenal vein thrombosis

Primary glomerular diseases:Primary glomerular diseases: Membranous GN (5, 40%), Lipoid Membranous GN (5, 40%), Lipoid Nephrosis (65, 15%), FSGS (10, 15%), Nephrosis (65, 15%), FSGS (10, 15%), MPGN (10, 7%), IgA nephropathyMPGN (10, 7%), IgA nephropathy

Systemic diseases: Systemic diseases: Diabetes, amyloidosis, SLE, Drugs Diabetes, amyloidosis, SLE, Drugs (Gold, penicillamine, heroin), (Gold, penicillamine, heroin), Infections (malaria, syphilis, Hepatitis Infections (malaria, syphilis, Hepatitis B, AIDS), Malignancy (carcinoma, B, AIDS), Malignancy (carcinoma, melanoma), Misc (bee sting, melanoma), Misc (bee sting, hereditary nephritis)hereditary nephritis)

Causes of NSCauses of NS

Membranous GNMembranous GN

Major cause of NS in adultsMajor cause of NS in adults Presence of electron dense, Ig Presence of electron dense, Ig

containing deposits subepithelial containing deposits subepithelial side of BMside of BM

Early: normal by light microscopy Early: normal by light microscopy Diffuse: thickening of capillary Diffuse: thickening of capillary wallwall

Secondary MGNSecondary MGN

Malignant epithelial tumors, carcinoma Malignant epithelial tumors, carcinoma lung, colon and melanomalung, colon and melanoma

SLESLE Exposure to inorganic salts (Gold, Exposure to inorganic salts (Gold,

mercury)mercury) Drugs (Penicillamine, Captopril)Drugs (Penicillamine, Captopril) Infections (Chr Hep B), syphilis, thyroiditisInfections (Chr Hep B), syphilis, thyroiditis Met. Disorders (GM, thyroidis)Met. Disorders (GM, thyroidis) 85% Idiopathic85% Idiopathic

Etiology/PathogenesisEtiology/Pathogenesis

Chr antigen-antibody mediated Chr antigen-antibody mediated diseasedisease

Secondary forms – specific antigens Secondary forms – specific antigens implicated – Exogenous/Endogenous implicated – Exogenous/Endogenous (thyroglobulin)(thyroglobulin)

Majority of patients antigens unknownMajority of patients antigens unknown Genetic susceptibilityGenetic susceptibility In situ immune reaction – glomerular In situ immune reaction – glomerular

or planted antigensor planted antigens Heymann’s nephritisHeymann’s nephritis Why capillaries are leaky? Membrane Why capillaries are leaky? Membrane

attack complex complentattack complex complent

MorphologyMorphology Early stages: normalEarly stages: normal Uniform, diffuse thickening of Uniform, diffuse thickening of

capillary wallcapillary wall

Clinical featuresClinical features

Insidious NS, 15% non-nephrotic Insidious NS, 15% non-nephrotic proteinuriaproteinuria

Hematuria/Mild HT – (15 – 35%)Hematuria/Mild HT – (15 – 35%) Course: indolentCourse: indolent Progression: increasing sclerosis, Progression: increasing sclerosis,

rising BUN, reduction of proteinuria, rising BUN, reduction of proteinuria, HT.HT.

Proteinuria persists 60%, 10% die, Proteinuria persists 60%, 10% die, 40% develop renal insufficiency40% develop renal insufficiency

Minimal change Minimal change diseasedisease Relatively benign disorderRelatively benign disorder Most frequent cause in childrenMost frequent cause in children Diffuse loss of foot processes of Diffuse loss of foot processes of

epithelial cellsepithelial cells Glomeruli virtually normal by light Glomeruli virtually normal by light

microscopymicroscopy Peak incidence: 2 – 6 yrsPeak incidence: 2 – 6 yrs

Etiology/ pathogenesisEtiology/ pathogenesis

Immunologic basis –Immunologic basis – Clinical asso with respiratory Clinical asso with respiratory

infections and immunizations infections and immunizations Response to steroid and Response to steroid and

immunosuppressive therapyimmunosuppressive therapy Asso with other atopic disordersAsso with other atopic disorders Increased prevalence of certain Increased prevalence of certain

HLA haplotypesHLA haplotypes

Increased incidence in HDIncreased incidence in HD Recurrence of proteinuria after Recurrence of proteinuria after

transplantationtransplantation

Minimal Change Minimal Change Disease:Disease:

Loss of Foot processes

Clinical featuresClinical features

ProteinuriaProteinuria Renal function goodRenal function good No HT or HematuriaNo HT or Hematuria 90% rapid response to steroids90% rapid response to steroids May recurMay recur Steroid dependentSteroid dependent Long term prognosis: excellantLong term prognosis: excellant

Focal segmental Focal segmental glomerulosclerosisglomerulosclerosis Sclerosis of some (focal) but not Sclerosis of some (focal) but not

all, glomeruliall, glomeruli Only a portion of capillary tuft Only a portion of capillary tuft

(segmental) is involved.(segmental) is involved. A) IdiopathicA) Idiopathic B) FSG superimposed on other B) FSG superimposed on other

primary GN (IgA nephropathy)primary GN (IgA nephropathy) C) Renal ablation FSGC) Renal ablation FSG Secondary FSG (HIV, Heroin)Secondary FSG (HIV, Heroin)

FSG..FSG..

10 - 15 % cases of 10 - 15 % cases of NSNS Hematuria, GFR, HTHematuria, GFR, HT Proteinuria: Non-selectiveProteinuria: Non-selective Poor response to steroidsPoor response to steroids Progress to Chr GNProgress to Chr GN IgM, C3 deposits IgM, C3 deposits

FSG..FSG.. Sclerotic segments: collapse of BMSclerotic segments: collapse of BM Increased mesangial matrixIncreased mesangial matrix Deposition of Hyaline masses Deposition of Hyaline masses

(Hyalinosis)(Hyalinosis) Lipoid dropletsLipoid droplets Diffuse loss of foot processesDiffuse loss of foot processes Pronounced, focal detachment of Pronounced, focal detachment of

epithelial cellsepithelial cells Denudation of underlying GBMDenudation of underlying GBM Hyaline thickening of afferent arteriolesHyaline thickening of afferent arterioles Global sclerosisGlobal sclerosis Tubular atrophy and interstial fibrosisTubular atrophy and interstial fibrosis

FSG: Clinical featuresFSG: Clinical features

No spontaneous remissionsNo spontaneous remissions Children : better prognosis.Children : better prognosis. Malignant focal sclerosis: 20% Malignant focal sclerosis: 20%

unusually rapid courseunusually rapid course HIV: Idiopathic FSG, focal cystic HIV: Idiopathic FSG, focal cystic

dilation of tubule segments, dilation of tubule segments, tubuloreticular inclusionstubuloreticular inclusions

Membranoproliferative Membranoproliferative GNGN Alteration in BM & proliferation of Alteration in BM & proliferation of

glomerular cellsglomerular cells Mesangiocapillary GNMesangiocapillary GN 5 – 10% idiopathic NS5 – 10% idiopathic NS Hematuria/proteinuriaHematuria/proteinuria Asso with systemic disorders, Asso with systemic disorders,

Primary or secondaryPrimary or secondary

MPGNMPGN

Glomeruli: large, HypercellularGlomeruli: large, Hypercellular Proliferation of mesangial cells, Proliferation of mesangial cells, Leukocytic infiltrate, parietal Leukocytic infiltrate, parietal

epithelial crescentsepithelial crescents Lobular appearance of glomeruliLobular appearance of glomeruli GBM thickenedGBM thickened

MPGNMPGN

Gomerular capillary wall shows Gomerular capillary wall shows ‘double contour’ or ‘Tram track ‘double contour’ or ‘Tram track apperence”apperence”

Splitting of BM due to extension Splitting of BM due to extension of processes of mesangial cells : of processes of mesangial cells : Mesangial interpositionMesangial interposition

Type I: Type I: Subendothelial electron Subendothelial electron dense depositsdense deposits

MPGNMPGN

Type IIType II: Deposition of dense : Deposition of dense material of unknown composition material of unknown composition in GBM properin GBM proper

C3 is present in granular linear C3 is present in granular linear foci and as foci and as mesangial ringsmesangial rings..

IgG absentIgG absent Type IIIType III: Subendothelial and : Subendothelial and

subepithelial depositssubepithelial deposits

MembranoproliferativeMembranoproliferative“tram-tracking”“tram-tracking”

MPGNMPGN

Type I: Immune complexes, Type I: Immune complexes, activation of classic and alternate activation of classic and alternate pathway of complementpathway of complement

Type II: Activation of alternate Type II: Activation of alternate pathway of complementpathway of complement

C3 Nephrtic Factor (C3NeF) in blood C3 Nephrtic Factor (C3NeF) in blood Presents as NSPresents as NS Progresses slowly but unremittinglyProgresses slowly but unremittingly Some develop RPGNSome develop RPGN 50% develop CRF in 10 years50% develop CRF in 10 years

Secondary MPGNSecondary MPGN

Usually of Type IUsually of Type I SLE, Hepatitis B, CSLE, Hepatitis B, C CryoglobulinemiaCryoglobulinemia Chronic liver diseaseChronic liver disease Certain malignanciesCertain malignancies SchistosomiasisSchistosomiasis

Chronic Chronic GlomerulonephritisGlomerulonephritis End stage pool of gomerular disease End stage pool of gomerular disease

-- RPGNRPGN Membranous GNMembranous GN Focal GlomerulosclerosisFocal Glomerulosclerosis MPGNMPGN IgA nephropathyIgA nephropathy Poststreptococcal is rare, othersPoststreptococcal is rare, others

MorphologyMorphology

Symmetrically contracted kidneysSymmetrically contracted kidneys Diffuse granular cortical surfaceDiffuse granular cortical surface Cortex is thinnedCortex is thinned Peripelvic fat is increasedPeripelvic fat is increased Hyaline obliteration of glomeruliHyaline obliteration of glomeruli Acellular, eosinophilic PAS-Acellular, eosinophilic PAS-

positive massespositive masses

Arterial arteriolar sclerosis: HTArterial arteriolar sclerosis: HT Atrophy of tubulesAtrophy of tubules Interstitial fibrosisInterstitial fibrosis Lymphocytic infiltrateLymphocytic infiltrate Stigmata of uremia: pericarditis, Stigmata of uremia: pericarditis,

gastroenteritis, renal gastroenteritis, renal osteodystrophy, LVH due to HT, osteodystrophy, LVH due to HT, Uremic pneumonitisUremic pneumonitis

Clinical featuresClinical features

Develops insidiouslyDevelops insidiously Nonspecific GI complaintsNonspecific GI complaints Finding of azotemia, proteinuria, Finding of azotemia, proteinuria,

HT on routine check upHT on routine check up EdemaEdema HT – CNS, CVS problemsHT – CNS, CVS problems Dialysis or transplantationDialysis or transplantation

False about NSFalse about NS

Proteinuria results from deranged Proteinuria results from deranged capillary wallscapillary walls

In selective proteinuria Albumin is In selective proteinuria Albumin is lostlost

HyperlipidemiaHyperlipidemia Vulnerability to infectionVulnerability to infection Bleeding complicationsBleeding complications

False about MCD..False about MCD..

Frequent cause of NS between 2 – Frequent cause of NS between 2 – 6 yrs6 yrs

Glomeruli show thickening of GBM Glomeruli show thickening of GBM by light microscopyby light microscopy

Immune deposits are not seenImmune deposits are not seen Tubules are ladden with lipids.Tubules are ladden with lipids.

FSGS: True or False FSGS: True or False Seen in Heroin abuse and HIVSeen in Heroin abuse and HIV Selective proteinuriaSelective proteinuria Respond well to steroidsRespond well to steroids Many Progress to chronic GNMany Progress to chronic GN Sclerotic segments show Sclerotic segments show

hyalinosis and lipoid droplets hyalinosis and lipoid droplets There is no podocyte fusionThere is no podocyte fusion Represents evolution of MCD Represents evolution of MCD

True

False

False

True

True

False

True

False about MPGN..False about MPGN.. Type I is commonType I is common Type I shows subendothelial Type I shows subendothelial

electron dense depositselectron dense deposits Type I is called dense deposit Type I is called dense deposit

diseasedisease In type II GBM is, irregular, ribbon-In type II GBM is, irregular, ribbon-

like structurelike structure Type I shows Immune complexesType I shows Immune complexes Type II has activation of alternate Type II has activation of alternate

complement pathwaycomplement pathway Secondary MPGN is usually type ISecondary MPGN is usually type I

Following commonaly Following commonaly leads to Chronic leads to Chronic Glomerulonephritis Glomerulonephritis exceptexcept RPGNRPGN Membranous GNMembranous GN MPGNMPGN Post-streptococcal GN in childrenPost-streptococcal GN in children

False about CGNFalse about CGN

Asymmetrically contracted Asymmetrically contracted kidneyskidneys

Thinned cortexThinned cortex Hyaline obliteration of glomeruliHyaline obliteration of glomeruli HypertensionHypertension Atrophy of tubulesAtrophy of tubules UremiaUremia

Which of the following Which of the following is a clinical feature of is a clinical feature of CGNCGN Loss of appetite, nausea,Loss of appetite, nausea, Proteinuria, HTProteinuria, HT EdemaEdema All of the aboveAll of the above

Spot the diagnosis…Spot the diagnosis…

FSGS

Spot the diagnosis…Spot the diagnosis…

CGN

Spot the diagnosis…Spot the diagnosis…

MGN

Spot the diagnosis…Spot the diagnosis…

MCD

Spot the diagnosis…Spot the diagnosis…

MPGN

Thought for the day…Thought for the day…

Life is like lemon & spoon race, if Life is like lemon & spoon race, if you drop the lemon there is no you drop the lemon there is no use coming first..use coming first..

Same is with life, where health Same is with life, where health and family are your lemon!and family are your lemon!

Thank you!Thank you!

Contact:Contact:

http://sachinkale1.tripod.com