Pathology of KidneyPathology of Kidney

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

Associate Professor, Dept of Associate Professor, Dept of Pathology.Pathology.

Anatomy of KidneyAnatomy of Kidney

Note the Note the positions of positions of

GlomerulusGlomerulus

PCT, PCT, DCT, CTDCT, CT

Cortex, Cortex, Medulla, Medulla, Pelvis.Pelvis.

Glomerular diseases:Glomerular diseases: PrimaryPrimary

– Acute diffuse post streptococcalAcute diffuse post streptococcal– RPGNRPGN– Membranous GNMembranous GN– FSGSFSGS– MPGNMPGN– Lipoid nephrosis or minimal changeLipoid nephrosis or minimal change– IgA nephropathyIgA nephropathy

SecondarySecondary– SLE, Diabetes, Amyloidosis, SLE, Diabetes, Amyloidosis,

Goodpasture’s syndrome, PAN, WG, Goodpasture’s syndrome, PAN, WG, HSP, Hypertension etc.HSP, Hypertension etc.

Clinical Syndromes:Clinical Syndromes: NeNephritic syndrome.phritic syndrome.

– Oliguria, Haematuria, Proteinuria, Oedema, Oliguria, Haematuria, Proteinuria, Oedema, Azotemmia, Hypertension.Azotemmia, Hypertension.

Nephrotic syndrome.Nephrotic syndrome.– >3.5 gm proteinuria, Hypoalbuminemia >3.5 gm proteinuria, Hypoalbuminemia

hyperlipidemia, Lipiduriahyperlipidemia, Lipiduria RPGN.RPGN.

– Nephritis, loss of Kidney function - within weeksNephritis, loss of Kidney function - within weeks Chronic renal failure.Chronic renal failure.

– Azotemia/uremia progressing over months and yearsAzotemia/uremia progressing over months and years Asymptomatic Hematuria or proteinuriaAsymptomatic Hematuria or proteinuria

Fluid and Electrolytes: Dehydration, Edema, Hyperkalemia, Metabolic acidosis

Calcium Phosphate and Bone: Hyperphosphatemia, Hypocalcemia, Secondary hyperparathyroidism, Renal osteodystrophy

Hematologic: Anemia, Bleeding diathesis

Cardiopulmonary: Hypertension, Congestive heart failure, Pulmonary edema, Uremic pericarditis

Gastrointestinal: Nausea and vomiting, Bleeding, Esophagitis, gastritis, colitis

Neuromuscular: Myopathy, Peripheral neuropathy, Encephalopathy

Dermatologic: Sallow (greenish-yellow) color, Pruritus, Dermatitis

CHRONIC RENAL FAILURE

ACUTE TUBULAR NECROSIS• Destruction of renal TUBULAR epithelium• Loss of renal function• 50% of ACUTE renal failure• Two types:

ISCHEMIC NEPHROTOXIC

-AMINOGLYCOSIDES

-AMPHOTERICIN B

-CONTRAST AGENTS

NORMAL

ATN

ATN PATHOGENESIS• BLOOD FLOW

DISTURBANCES (ISCHEMIC)

• TUBULAR INJURY (NEPHROTOXIC)

CLINICAL COURSE• INITIATION (36 hours)

– Mild OLIGURIA– Mild AZOTEMIA

• MAINTENANCE– More OLIGURIA– More AZOTEMIA– DIALYSIS NEEDED

• RECOVERY– HYPOKALEMIA main problem– BUN, CREATININE return to normal

Immune Mechanisms Immune Mechanisms of Glomerular injury:of Glomerular injury:

Antibody mediatedAntibody mediated:: In-Situ immune complex depositionIn-Situ immune complex deposition

– Tissue antigens - Goodpasture anti GBM AgTissue antigens - Goodpasture anti GBM Ag– Planted antigens - infections, toxins, drugs.Planted antigens - infections, toxins, drugs.

Circulating immune complex deposition.Circulating immune complex deposition.– Endogenous - DNA as in SLEEndogenous - DNA as in SLE– Exogenous – infections – HBsAg, Syphilis, Exogenous – infections – HBsAg, Syphilis,

Streptococcal, Falciparum,Streptococcal, Falciparum, Cell mediated Immune injuryCell mediated Immune injury Activation of alternate complement Activation of alternate complement

pathwaypathway

Immune Immune Glomerulonephritis:Glomerulonephritis:

1.1. Antigen or Antibody - Immune Antigen or Antibody - Immune reactionreaction

2.2. Activation of complements, Activation of complements, Neutrophils…Neutrophils…

3.3. destruction of glomerular structuredestruction of glomerular structure

4.4. Inflammation, exudation Inflammation, exudation swelling. swelling.

5.5. ↓ ↓ blood flow, GFR, - blood flow, GFR, -

6.6. Oliguria, Proteinuria, Hematuria, Oliguria, Proteinuria, Hematuria, Hypertension.Hypertension.

Neutrophil ActivityNeutrophil Activity

Proteases – GBM degradationProteases – GBM degradation Reactive oxygen metabolites – cell damageReactive oxygen metabolites – cell damage Arachidonic acid metabolites –Reduction in Arachidonic acid metabolites –Reduction in

GFRGFR

Other MediatorsOther Mediators

Cytotoxic antibodiesCytotoxic antibodies MacrophagesMacrophages PlateletsPlatelets Resident glomerular cellsResident glomerular cells Fibrin related productsFibrin related products

Nephritic Syndromes :Nephritic Syndromes :

Diffuse Proliferative GNDiffuse Proliferative GN– Post Streptococcal.Post Streptococcal.

Rapidly Progressive GN (or Crescentic)Rapidly Progressive GN (or Crescentic)– Post Streptococcal, Goodpasture’s, Post Streptococcal, Goodpasture’s,

Focal GlomerulonephritisFocal Glomerulonephritis– Primary: Bergers disease (IgA Nephritis)Primary: Bergers disease (IgA Nephritis)– Secondary IgA nephritis, Henoch Schonlein Secondary IgA nephritis, Henoch Schonlein

purpura, SBE, Coeliac Disease etc.purpura, SBE, Coeliac Disease etc.

Diffuse Proliferative Diffuse Proliferative GN:GN: Post streptococcal* common – Post streptococcal* common – Primary infection - Pharynx, skin, Primary infection - Pharynx, skin,

ear etc.. ear etc.. Kidney damage – 1-4 weeks after Kidney damage – 1-4 weeks after

infection.infection. Malaise, fever, nausea, edema*, Malaise, fever, nausea, edema*,

↑↑ASO, ASO, ↓C3↓C3 Resolution in 6-8 weeks.Resolution in 6-8 weeks.

Post Streptococcal GN Post Streptococcal GN (Prol.GN):(Prol.GN): 1-4 weeks following streptococcal 1-4 weeks following streptococcal

infection by nephritogenic strains infection by nephritogenic strains (time for Ab formation)(time for Ab formation)

Immune mediatedImmune mediated Granular deposits of IgG,IgM & C3 in Granular deposits of IgG,IgM & C3 in

GBM, (subepithelial location common)GBM, (subepithelial location common) Humps in GBM on EM or IF MicroscopyHumps in GBM on EM or IF Microscopy

•Normal

•Inflammation

•Proliferation

•Swelling.

•Narrow capillary

•↓GFR-Renin-BP•Post Strepto GN

Diffuse Proliferative Diffuse Proliferative GN:GN:

Enlarged hypercellular Enlarged hypercellular glomeruli.glomeruli.

Hyperplasia of epithelium Hyperplasia of epithelium & endothelium. Cell & endothelium. Cell Swelling.Swelling.

Inflammatory cells.Inflammatory cells. Collapsed capillaries. Collapsed capillaries.

Obstruction to blood Obstruction to blood flow.flow.

IF- Diffuse IF- Diffuse Proliferative GNProliferative GN

Pathogenesis of Pathogenesis of Diffuse PGN:Diffuse PGN:

Streptococcal infection – Antibody Streptococcal infection – Antibody attack GBM - inflammation & attack GBM - inflammation & proliferation.proliferation.

Glomerular capillary obstruction:Glomerular capillary obstruction:– J.G.A stimulation – Renin – high blood J.G.A stimulation – Renin – high blood

pressurepressure– Reduced filtration – raised blood ureaReduced filtration – raised blood urea– Fluid retention – OedemaFluid retention – Oedema

Damage to GBM:Damage to GBM:– Unselective proteinuria (form Pr. casts in Unselective proteinuria (form Pr. casts in

tubule)tubule)– Haematuria (form RBC casts in tubule)Haematuria (form RBC casts in tubule)

Progression of DPGN:Progression of DPGN:

PoststreptococcaPoststreptococcal DPGNl DPGN

CGNCGNCardiac Failure or Uremia; death in acute phase

Complete HealingComplete Healing

Rapidly Progressive GN

RPGNRPGN

Clinicopathologic syndromeClinicopathologic syndrome Glomerular damageGlomerular damage Rapid progressive decline in renal Rapid progressive decline in renal

functionfunction Histology: accumulation of cells in Histology: accumulation of cells in

Bowman’s space in the form of Bowman’s space in the form of “Crescents”“Crescents”

RPGN: Classification & RPGN: Classification & PathogenesisPathogenesis PostinfectiousPostinfectious GN associated with systemic GN associated with systemic

diseasesdiseases Idiopathic RPGNIdiopathic RPGN Glomerular injury is Glomerular injury is

immunologically mediated.immunologically mediated. Goodpasture’s syndrome – classic Goodpasture’s syndrome – classic

anti-GBM nephritisanti-GBM nephritis

RPGN classificationRPGN classification

Post-infectious RPGNPost-infectious RPGN Systemic diseases –Systemic diseases –

– SLE, Goodpasture’s, Vasculitis (PAN), SLE, Goodpasture’s, Vasculitis (PAN), Wegener’s granulomatosus, HSP, Wegener’s granulomatosus, HSP, Essential cryoglobulinemiaEssential cryoglobulinemia

Idiopathic RPGNIdiopathic RPGN

RPGN cont..RPGN cont..

Idiopathic : ½ the cases,Idiopathic : ½ the cases, Linear, Granular or minimal to Linear, Granular or minimal to

none immune depositsnone immune deposits Gross: Enlarged pale kidneys Gross: Enlarged pale kidneys Large Large

white kidneywhite kidney Petechial hemorrhages in cortexPetechial hemorrhages in cortex M/E: Glomeruli: focal necrosis, M/E: Glomeruli: focal necrosis,

endothelial proliferationendothelial proliferation

RPGN…RPGN…

Formation of crescents: Formation of crescents: Proliferation of parietal cells, Proliferation of parietal cells,

migration of monocytes and migration of monocytes and macrophages into Bowman’s macrophages into Bowman’s spacespace

Crescents obliterate Bowman’s Crescents obliterate Bowman’s space, compression capillary tuftspace, compression capillary tuft

Crescents undergo sclerosisCrescents undergo sclerosis

RPGN: Clinical featuresRPGN: Clinical features

Goodpasture’s Syndrome: Goodpasture’s Syndrome: recurrent hemoptasis & renal recurrent hemoptasis & renal manifestationsmanifestations

Hematuria, Red cell casts, Hematuria, Red cell casts, Moderate proteinuria,Moderate proteinuria,

Variable HT and edemaVariable HT and edema OliguriaOliguria

Which of the following Which of the following presents with hematuria, presents with hematuria, proteinuria and proteinuria and hypertensionhypertension

Nephrotic syndromeNephrotic syndrome Nephritic SyndromeNephritic Syndrome UTIUTI Renal Tubular AcidosisRenal Tubular Acidosis

All of the following are All of the following are seen in renal failure seen in renal failure exceptexcept

HypercalcemiaHypercalcemia HyperkalemiaHyperkalemia Bone lesionsBone lesions Metobolic AcidosisMetobolic Acidosis

Anemia in renal failure Anemia in renal failure is generallyis generally Microcytic hypochromicMicrocytic hypochromic Normocytic normochromicNormocytic normochromic DimorphicDimorphic megaloblasticmegaloblastic

Which of the following Which of the following is not a primary GNis not a primary GN Minimal Change diseaseMinimal Change disease Membranous GNMembranous GN Diabetes mellitusDiabetes mellitus RPGNRPGN

Which of the following is Which of the following is not part of nephrotic not part of nephrotic syndromesyndrome LipiduriaLipiduria HypertensionHypertension ProteinuriaProteinuria Edema Edema

True about Post-True about Post-strepto GN -strepto GN -

Occurs 1 – 4 months after Occurs 1 – 4 months after infectioninfection

Occurs 1 – 4 days after infectionOccurs 1 – 4 days after infection Occurs 1 – 4 weeks after infectionOccurs 1 – 4 weeks after infection Non of the aboveNon of the above

False about RPGN..False about RPGN..

Formation of crescentsFormation of crescents Small contracted kidneysSmall contracted kidneys HematuriaHematuria OliguriaOliguria

Spot the diagnosisSpot the diagnosis

RPGN

Spot the diagnosisSpot the diagnosis

ATN

Spot the diagnosisSpot the diagnosis

Poststreptococcal GN

Thought for the day…Thought for the day…

Ours is a world where people Ours is a world where people don't know don't know what they want and are willing to what they want and are willing to go go through hell to get it. through hell to get it. 

Thanks…Thanks…

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