Preface

Agam is a group of budding medicos, who are currently doing their under graduation in
various Medical Colleges across Tamil Nadu and Pondicherry. The group was initiated on 18th
November 2017, in the vision of uniting medicos for various social and professional causes.

We feel delighted to present you Agam Pathology notes prepared by Agam Divide and Rule
2020 Team to guide our fellow medicos to prepare for university examinations.

This is a reference work of 2017 batch medical students from various colleges. The team
took effort to refer many books and make them into simple notes. We are not the authors of the
following work. The images used in the documents are not copyrighted by us and is obtained from
various sources.

Dear readers, we request you to use this material as a reference note, or revision note, or
recall notes. Please do not learn the topics for the 1st time from this material, as this contain just the
required points, for revision.
Acknowledgement

On behalf of the team, Agam would like to thank all the doctors who taught us Pathology.
Agam would like to whole heartedly appreciate and thank everyone who contributed towards the
making of this material. A special thanks to Vignesh M, who took the responsibility of leading the
team. The following are the name list of the team who worked together, to bring out the material in
good form.

• Neelavathi S
• Artheshivani S M
• Sowmya T D
• Jeyendra Jayanth M
• Keerthana Muthuraman
• Kirubhahari C
• Pavithra Devi K
• Prasanna Sri P
• Swathikrishna S
• Daleesh D
• Dharani D
• Habeeb Nathira
• Krishna Priyaa S
• Swathika N G
• Vennmadhi Vellentina D
• Diptha Viswanathan
• Dhanshree Bakhru
• Yashwantha Elumalai Jagadeesan
• Vignesh. M
 THE KIDNEY
ESSAY:
1. Nephrotic syndrome
2. Nephritic syndrome
3. Chronic pyelonephritis
4. Mechanism of glomerular injury in primary glomerular diseases
5. Post-streptococcal glomerulonephritis.
SHORT NOTES:
1. Pathogenesis of Carcinoma kidney
2. Renal cell carcinoma
3. Difference between nephrotic and nephritic syndrome
4. Nephrosclerosis
5. Cystic lesions of kidney
6. Autosomal Dominant Polycystic kidney disease
7. Wilms tumor
8. Acute pyelonephritis
9. Chronic pyelonephritis
10.Immune complex nephritis
11.Renal stones
12.Acute tubular necrosis
13.Proteins in urine
SHORT ANSWERS:
1. Microscopic changes of chronic pyelonephritis
2. Myeloma kidney
3. Grading of urothelial malignancy
4. Pathogenesis of Renal edema
5. Importance of casts in urine
6. Urinary casts
7. Clear cell carcinoma of kidney
8. Contracted granular kidney
9. Autosomal Recessive Polycystic kidney disease
UPDATES

AGAM PATHOLOGY
ESSAY
1. NEPHROTIC SYNDROME
PATHOPHYSIOLOGY:
 Caused by derangement of glomerular capillary walls resulting in ↑ permeability to
plasma proteins.
 Main plasma protein lost-albumin (selective proteinuria)
 To compensate the loss, liver produces less proteins, as a result lesser lipoprotein
produced. Increased free lipid → hyperlipidemia.

CLINICAL FEATURES:
 Foamy urine – lipid may be as free fat or oval fat bodies.
 Massive proteinuria – loss of 3.5 g or more of protein within 24hrs
 Highly selective proteinuria – contain low molecular weight proteins
 Poorly selective proteinuria – contain high molecular weight proteins.
 Hypo albuminemia – plasma albumin = 1-3 gm/ dl. Normal range (3.5-5.5 gm/dl).
 Generalized edema – due to ↓ plasma oncotic & ↑ capillary hydrostatic pressure.
 Hyperlipidemia and lipiduria –due to compensatory activity of liver
 Na & H2O retention aggravates the periorbital edema.
 Hypercoagulability- spontaneous arterial & venous thrombosis is seen. Due to many
factors - loss of Antithrombin III, decreased fibrinolysis, Platelet aggregation,
 Hyperfibrinogenemia, altered C & S protein levels.
CAUSES:
Primary causes: Due to kidney lesions, they include;
 Membranous glomerulonephritis
 Minimal change disease
 Focal segmental glomerulosclerosis
 Membranoproliferative glomerulonephritis
 Ig A Nephropathy
Secondary causes:
 Systemic diseases:  Systemic infections:
 Diabetes mellitus  Viral Infections (HIV, HBV, HCV)
 Amyloidosis  Bacterial infections
 SLE 

AGAM PATHOLOGY
COMPLICATIONS:
 Pleural effusion
 Ascites
 Thrombotic and thromboembolic complications –due to loss of anticoagulants
 Renal vein thrombosis

A. MEMBRANOUS NEPHROPATHY:
 Characterised by deposits of subepithelial immunoglobulin containing spikes.
 In well-developed cases, diffuse thickening of glomerular capillary wall.
 It is due to the presence of circulating autoantibodies against podocyte antigen- Anti
Phospho-Lipase A2 Receptor Antigen (Anti-PLA2R)
 This is secondary to- any systemic infections / diseases or any other malignancies.

PATHOGENESIS:
 It is a chronic immune complex mediated disease, mainly Membrane Attack Complex
(MAC)

Immune complex deposits activate glomerular epithelial and mesangial cells

Induces the release of proteases and oxidants with activation of complement system

Cause capillary wall injury

Glomerular basement membrane damaged by immune complex deposits

↑ Protein leakage

Nephrotic syndrome

TYPES:
 Primary membranous nephropathy:
 Autoimmune disease linked to HLA allele like HLA-DQ1 .
 IgG4 is the principal immunoglobin deposited.

AGAM PATHOLOGY
 Secondary membrane nephropathy:
 Here autoantibodies are generated in response to following conditions.
 Infections –Hepatitis B, Hepatitis C virus, Syphilis
 Drugs – NSAIDS, penicillin,
 Autoimmune diseases-SLE
 Malignancy
 Autoantibodies that target glomerular basement membrane
 M –type phospholipase A2 receptor
 Neural endopeptidase

MORPHOLOGY: Grossly, the kidneys are enlarged, pale & smooth

LAB DIAGNOSIS:
 Light microscopy:
 Uniform diffuse thickening of glomerular capillary wall.
 Thickened basement membrane with Fibrosis of the interstitium.
 Thickening is caused by immune complex deposits (electron dense deposits) between
basement membrane and epithelial cells
 Electron microscopy:
 Irregular spikes protruding from basement membrane.
 These spikes further develop dome like protrusions and buries the immune deposits
within them
 These deposits contain both immunoglobulins and complement.
 Progressively sclerosis of glomeruli occurs.
 Immuno fluorescence:
 Granular appearance that shows deposits of IgG with complement C3

CLINICAL FEATURES:
 Hematuria
 Hypoalbuminuria
 Edema
 Mild HT
 Non selective proteinuria
 Lipiduria
 Hypercoagulability
 Renal insufficiency

AGAM PATHOLOGY
B. FOCAL SEGMENTAL GLOMERULOSCLEROSIS:
 Incidence- 1/3rd cases of nephrotic syndrome in adults.
 Characterised by sclerosis and hyalinosis that involves only part of capillary tuft of
some glomeruli

PATHOGENESIS:
 Visceral epithelial damage (due to circulating factors and genetically determined defects)
is the hallmark of FSGS.
 It represents are subset minimal change disease due to similar regeneration.

Proteins get Buildup inside Scar Glomerulo-

Hyalinosis
trapped glomeruli Tissue sclerosis

CLASSIFICATION:
 Primary:  Other causes:
 Idiopathic  Congenital anomalies eg: renal dysplasia
 Secondary causes:  Acquired causes eg: reflux nephropathy
 Viruses: HIV infection  Mutations of NPHS1 & NPHS2, actinin-4 & apo –L1
 Drugs: Heroin addiction genes
 Sickle cell disease

RISK FACTORS:
 Obesity
 More common in blacks of American descent
 Chronic kidney disease

CLINICAL FEATURES:
 Hypoalbuminaemia  Proteinuria
 Hyperlipidemia  Edema
 Hypercoagulability  Lipiduria
 Poor response to corticosteroid therapy
 Complications: End stage renal failure

MORPHOLOGY:
 Collapsing glomerulopathy
 Diffuse loss of foot processes

AGAM PATHOLOGY
LABORATORY DIAGNOSIS:
 Urine protein > 3.5 g/l
 Light microscopy: Hyalinosis, segmental sclerosis of one or more lobules of tuft of
glomeruli.
 Electron microscopy: diffuse loss of foot processes of podocytes with Ig deposits.
 Immunofluorescence: Non-specific focal deposits of IgM and C3 (sometimes not visible if
trapped in hyalinosis)

C. MINIMAL CHANGE DISEASE:

 Benign disorder
 Type of glomerulonephritis that is most common in children.

PATHOGENESIS:
 Immunologic mechanism: Foot processes of podocytes are damaged by cytokines
secreted by T cells → Albumin permeates but bigger proteins can’t penetrate through
(selective proteinuria)
 Non immunological mechanism: Due to injury to visceral epithelial cells due to:
 Mutation in structural proteins like nephrin, podocin
 Mutation in the Nephrin gene

MORPHOLOGY:
 Kidneys are mildly enlarged, cut section shows pale to yellow cortex.
 Lipoid nephrosis

LAB DIAGNOSIS:
 Protein in urine > 3.5 g/day
 Light microscopy: Glomeruli appear normal; PCT shows lipid vacuoles in cytoplasm.
 Electron microscopy: Uniform and diffuse effacement of foot processes.
 Immunofluorescence: No immune complex deposition.

CLINICAL FEATURES:
 More rapid onset than other nephrotic syndromes
 Selective proteinuria  Edema
 Hypoalbuminemia  Hyperlipidemia

AGAM PATHOLOGY
D. MEMBRANO PROLIFERATIVE GLOMERULONEPHRITIS:
PATHOLOGY: Immune mediated injury seen

Immune complex activates complement system

Protease and oxidase release

Damage to podocytes and mesangial cells

Inflammation of GBM & mesangium

Decreased kidney function

Proteinuria

Nephrotic Syndrome

RISK FACTORS:
 Dysregulation of complement system
 Immune suppression

TYPE 1: Causes:
 Secondary to Chronic infections- HIV, HBV, HCV, Bacterial Endocarditis
 Systemic Diseases- SLE, mixed cryoglobulinaemia, Sjögren’s syndrome
 Malignancies- Lymphomas & Leukemias

TYPE 2: (also called dense deposit disease)

 Belongs to a group of disorders called C3 glomerulopathies
 due to mutation of factor C3NeF
 due to excessive activation of alternative complement pathway
 C3 is present in GBM but not on dense deposits

AGAM PATHOLOGY
 Antibody against Nephritic factor (C3NeF)

Binds C3 convertase of alternate pathway

More stable C3 convertase

Protect from inactivation

Hypocomplementemia

CLINICAL FEATURES:
 Has the symptoms of both nephritic and nephrotic syndrome
 Nephrotic syndrome symptoms:  Nephritic syndrome symptoms:
o Proteinuria o Hematuria
o Peripheral edema o Oliguria
o Foamy urine o HT
o Hypolipidemia
o Lipiduria
 Complications: Chronic renal failure

MORPHOLOGY:
 Glomeruli are large and hypercellular, have a ’lobular appearance’ due to proliferation
mesangial cells and increased mesangial matrix.
 GBM thickened - Tram track appearance
 Leukocyte infiltration
 Type1:
 Subendothelial electron deposits
 IgG &C3 are deposited in granular pattern
 Type 2:
 Complement deposits along GBM
 Intra membranous deposit (ribbon like homogenous electron dense material)

AGAM PATHOLOGY
TREATMENT:
 Immunosuppressive therapy
 Antiviral therapy
 Antiplatelet drugs

E. HIV ASSOCIATED NEPHROPATHY:

 A high frequency of collapsing variant of FSGS
 Seen in 5-10 % of HIV patients
 Now the incidence of this lesion is very much reduced.
MORPHOLOGY:
 Focal cystic dilation of tubule filled with proteinaeceous material, inflammation, fibrosis.
 Presence of large number of tubulo reticular inclusions within sub endothelial cells.
COMPLICATIONS:
 Acute renal failure  Thrombotic micro angiopathies
 Acute interstitial nephritis  Post infectious glomerulonephritis

2. NEPHRITIC SYNDROME:
 Characterized by inflammation of glomerulus

Nephritic Syndrome

Acute Proliferative Glomerulonephritis Rapidly progressive (crescentic)

glomerulonephritis
 Post- streptococcal glomerulonephritis
 Post- infectious glomerulonephritis  Type 1: Anti GBM antibody
(Non-Streptococcal Acute Glomerular  Type 2: Immune complex deposition
Nephritis)  Type 3: Pauci immune

ACUTE PROLIFERATIVE GLOMERULONEPHRITIS:

 Immune complex mediated disorder where the antigen can be exogenous or
endogenous
 Also occur in multisystem diseases like SLE, microscopic polyangiitis (endogenous antigen
involved)
 Diffuse proliferation of glomerular cells with influx of leukocytes is seen.

AGAM PATHOLOGY
POST STREPTOCOCCAL GLOMERULONEPHRITIS:
 Immune complex mediated glomerular disease.
 It appears 1-4 weeks after a streptococcal infection of pharynx or skin. Streptococcal
pyogenic exotoxin Spe –B is the antigenic determinant in most of the cases.
RISK FACTORS:
 Overcrowding and poor hygiene.
 6-10 years of children and adults of any age.
 MORPHOLOGY: Grossly, Flea-Bitten appearance of symmetrically enlarged kidneys-
sign of petechial hemorrhages
HISTOLOGY:
 Enlarged hypercellular glomeruli.
 Infiltration of leukocytes (both neutrophils and monocytes)
 Proliferation of endothelial and mesangial cells.
 Swelling of endothelial cells
 Interstitial edema and inflammation may be present .
 Tubules contain red cell casts
IMMUNOFLUORESCENT MICROSCOPY:
 Shows granular deposits of IgG and C3. sometimes, IgM
 Focal and sparse arrangement
ELECTRON MICROSCOPY :
 Amorphous electron dense deposits on epithelial side of basement membrane.
 Hump like appearance.
 Sub-endothelial deposits are seen.
 Mesangial and intramembranous deposits may be present.
LABORATORY FINDINGS:
 ↑antistreptococcal antibody titers like- ASO, Anti-DNAase B, ASKase , Anti-NADase
 ↓ serum C3 concentration
 Elevation of BUN
CLINICAL FEATURES:
 Hematuria ⇒ Smoky red or cola coloured urine ⇒ Red cell casts are present.
 Proteinuria  Malaise
 Periorbital edema  Fever
 Mild to moderate HT  Nausea
 Oliguria
COMPLICATIONS: Chronic glomerulonephritis

AGAM PATHOLOGY
POST INFECTIOUS GLOMERULONEPHRITIS:
 Caused due to infections like:
 Bacterial infections (eg: pneumococcal pneumonia, meningococcemia)
 Viral infections (eg; hepatitis b, hepatitis c, mumps, varicella, HIV)
 Parasitic infections (eg; malaria, toxoplasmosis)
MORPHOLOGY:
 Granular immune fluorescent deposits (sometimes IgA deposits are formed rather
than IgG)
 Subepithelial hump

RAPIDLY PROGRESSIVE (CRESCENTRIC) GLOMERULONEPHRITIS:

 Syndrome associated with severe glomerular injury.
 Auto immune mediated or immune complex deposition

MICROSCOPY: Presence of casts in most of glomeruli

CLASSIFICATION:
 Anti GBM antibody mediated disease – type 1
 Renal limited
 Good pasture syndrome: Pulmonary hemorrhage + renal failure due to anti GBM
antibodies cross reaction
 Treatment: Plasmapheresis
 Immune complex deposition – type 2
 Idiopathic (or) May be due to:
 Post infectious glomerulonephritis,
 Lupus nephritis
 Henoch –Schönlein purpura
 IgA nephropathy
 Pauci immune RPGN – type 3
 Includes granulomatosis with polyangitis (Wegener granulomatosis)
 Anti-Neutrophil Cytoplasmic Antibody (ANCA) associated
 Idiopathic
 Microscopic polyangiitis

AGAM PATHOLOGY
MORPHOLOGY OF RPGN:
 Enlarged and pale kidney with petechial hemorrhage on cortex.
 Focal or segmented necrosis of glomeruli.
 Endothelial proliferation
 Mesangial proliferation

HISTOLOGY:
 Distinctive crescents are formed due to proliferation of parietal cells and by migration
of monocytes.
 Lymphocytes and neutrophils are seen.
 Presence of fibrin strands.

IMMUNOFLUORESCENCE:
 Granular immune deposits
 Good pasture syndrome → has linear GBM fluorescence for Ig and complement
 Pauci immune cases → have no immune complex deposition

ELECTRON MICROSCOPY:
 Wrinkling of GBM is seen.
 Shows rupture in GBM which causes leukocytes, complements, coagulation factors
inflammatory mediators to reach urinary space and to trigger crescent formation.

CLINICAL FEATURES:
 Hematuria with red cell casts
 Proteinuria
 Oliguria
 Hypertension &edema
 Recurrent hemoptysis and pulmonary hemorrhage-seen in good pasture syndrome

TREATMENT:
 Plasmapheresis
 With steroids and cytotoxic agents

AGAM PATHOLOGY
3. CHRONIC PYELONEPHRITIS
 Chronic pyelonephritis is a disorder in which chronic tubulointerstitial inflammation and
scarring involving the renal calyces and pelvis .
 An important cause of kidney destruction in children with severe lower urinary tract
abnormalities.
 Diagnostic clue : Only chronic pyelonephritis and analgesic nephropathy affect the
calyces, making pelvocalyceal damage.

CLASSIFICATION:
REFLUX NEPHROPATHY CHRONIC OBSTRUCTIVE PYELONEPHRITIS
More common form of chronic Scarring is not so common
pyelonephritic scarring
Occurs early in childhood as a result Occurs in adulthood mostly
of superimposition of a urinary
infection on congenital vesicoureteral
reflux and intrarenal reflux
Can be Unilateral or Bilateral, latter Unilateral - in calculi and unilateral obstructive
leads to chronic renal insufficiency anomalies of the ureter. Bilateral - with posterior
urethral valves (a congenital anomaly)
Continuous renal damage causes Recurrent infections superimposed on diffuse or
scarring and atrophy localized obstructive lesions lead to repeated bouts
of renal inflammation and scarring
Vesicoureteral reflux occasionally Obstruction predisposes the kidney to infection and
causes renal damage in the absence contributes to parenchymal atrophy
of infection (sterile reflux), but only
when obstruction is severe

MORPHOLOGY:
Gross :
 Irregularly scarred
 If bilateral, the involvement is asymmetric
 Hallmarks of chronic pyelonephritis are : Coarse, discrete, corticomedullary scars
overlying dilated, blunted, or deformed calyces, and flattening of the papillae.

AGAM PATHOLOGY
Microscopic changes:
 Tubules - Atrophy in some areas and hypertrophy or dilation in others.
 Thyroidization - Dilated tubules with flattened epithelium filled with casts resembling
thyroid colloid.
 Varying degrees of chronic interstitial inflammation and fibrosis in the cortex and
medulla.
 Arcuate and interlobular vessels demonstrate obliterative intimal sclerosis in the scarred
areas.
 In the presence of hypertension :
 Hyaline arteriolosclerosis is seen in the entire kidney.
 Fibrosis around the calyceal epithelium as well as a marked chronic inflammatory
infiltrate.
 Glomeruli may appear normal except for a variety of ischemic changes, including
periglomerular fibrosis, fibrous obliteration and secondary changes related to
hypertension.
 Individuals with chronic pyelonephritis and reflux nephropathy who develop proteinuria
in advanced stages show secondary focal segmental glomerulosclerosis with significant
proteinuria .

XANTHOGRANULOMATOUS PYELONEPHRITIS:
 Relatively rare form of chronic pyelonephritis characterized by accumulation of foamy
macrophages intermingled with plasma cells, lymphocytes, polymorphonuclear
leukocytes, and occasional giant cells.
 Often associated with Proteus infections and obstruction, the lesions sometimes produce
large, yellowish orange nodules that may be grossly confused with renal cell carcinoma.

CLINICAL FEATURES:
 Silent onset
 Presentation with manifestations of acute recurrent pyelonephritis, such as back pain,
fever, pyuria, and bacteriuria.
 Gradual onset of renal insufficiency and hypertension.
 Reflux nephropathy is often the cause of hypertension.
 Loss of tubular function (concentrating ability)—gives rise to polyuria and nocturia.

AGAM PATHOLOGY
LAB DIAGNOSIS:
 Urinalysis & Culture: Significant bacteriuria may be present, but it is often absent in the
late stages.
 Radiographic studies: show asymmetrically contracted kidneys with characteristic coarse
scars and blunting and deformity of the calyceal system.
DIFFERENTIAL DIAGNOSIS:
 Analgesic abuse nephropathy
 Renal tuberculosis
 Renal dysplasia
COMPLICATIONS :
 Focal glomerulosclerosis, attributable to the adaptive glomerular alterations secondary
to loss of renal mass caused by pyelonephritic scarring (renal ablation nephropathy).
 Progressive renal scarring leading to end stage renal disease.
 Proteinuria
TREATMENT: Elimination of obstruction (Correction of any structural disorders)
PROGNOSIS: The onset of proteinuria and focal segmental glomerulosclerosis is a poor
prognostic sign, which may progress to End Stage Renal Disease (ESRD).

AGAM PATHOLOGY
4. PATHOGENESIS OF PRIMARY GLOMERULAR INJURY
 Immune mechanisms (by immune complexes) are the most common underlying
pathology of primary glomerulopathy.
 Components of complement system are also often associated with antigen-antibody
complexes.
 Cell mediated immunity also plays an important role.
 Two forms of immune complexes associated injury are identified:
 Injury by antibodies reacting in situ within glomerulus, either with intrinsic glomerular
proteins or with planted antigens.
 Injury associated with deposition of circulating antigen-antibody complexes in the
glomerulus.
 Major cause of primary glomerulopathy is due to formation of immune complexes in situ
in the glomerulus.

Immune mechanism of cellular injury in glomerulus

Antibody Mediated Immune Complex Mediated

Fixed Antigens Planted Antigen Endogenous Exogenous

Antigens Antigens
 NC1 domain products Exogenous
(Anti- GBM nephritis)  Drugs  DNA Infectious
 Heymann antigen  Infectious agent  Tumour agents
 Mesangial antigens Endogenous: Antigens
 DNA
 Nuclear protein

Glomerulopathy by Insitu Formation of Immune Complexes:

 Immune complexes are formed locally within the glomerulus triggered by either intrinsic
tissue antigens or by extrinsic ‘planted’ antigens.

AGAM PATHOLOGY
Membranous Nephropathy:
 It is a classic example for glomerulopathy resulting from in situ immune complexes
formation.
 Intrinsic antigen involved in membranous glomerulopathy is a phospholipase A2 receptor
- PLA2R antigen present in the glomerular epithelial cells membrane.
 Thickened glomerular basement membrane (GBM) is seen because of deposition of
immune complexes along the subepithelial side of the membrane.
 Immunofluorescence microscopy shows large discrete granular deposits of complexes
along subepithelial side if GBM.
 Membranous nephropathy can be primary (autoimmune) or secondary (induced by
drugs or graft-versus-host disease).

Anti-GBM Nephritis (Anti-GBM Antibody Induced Glomerulonephritis):

 In this variant of nephritis antibodies are directed against the components of glomerular
basement membrane.
 Immune complexes thus formed are homogenously distributed along the entire length of
GBM.
 Immunofluorescence shows diffuse linear deposits in the GBM.
 Most common intrinsic antigen involved is NC1 domain of type IV collagen.
 Antibodies produced often cross-react with other basement membranes, like in lung
alveoli.
 Goodpasture syndrome shows anti-GBM nephritis pattern in which lesions are formed in
both lung and kidney basement membranes.
 Anti-GBM nephritis can progress to severe necrotizing and crescent forming
glomerulopathy.

Antibodies against Planted/Extrinsic Antigens:

 Planted antigens include cationic molecules, DNA, nucleosomes, large aggregated
proteins and bacterial products.
 They react with antibodies and form immune complexes within the glomeruli.
 Immunofluorescence show discrete granular deposits same as endogenous antigens.

AGAM PATHOLOGY
Glomerulopathy by Deposition of Circulating Immune Complexes:
 Glomerular injury is cause by trapping of circulating antigen-antibody complexes within
glomeruli.
 Antibodies have no immunologic specificity for glomerular antigens.
 Immune complexes are just localized within the glomeruli because of hemodynamic
factors of glomeruli.
 Trigger for immune complexes formation can be endogenous (SLE, Ig-A nephropathy) or
exogenous (post infectious).
 Microbial exogenous antigens are: Streptococcal proteins (PSGN),
 Surface antigens of HBV, HCV, Antigens of Treponema, Plasmodium.

Mechanism of Glomerular Injury by Immune Complexes:

 Local inflammatory response caused by immune complexes are responsible for
producing glomerular injury
 After deposition these complexes are degraded by infiltrating leukocytes, macrophages,
mesangial cells and release of pro-inflammatory cytokines and growth factors takes
place.
 Glomerular lesions include leukocytic infiltration and proliferation of mesangial and
endothelial cells.
 Electron microscope reveals that immune complexes can be lodged in:
 Mesangium
 Subendothelial deposits (between endothelium and GBM)
 Subepithelial deposits (between GBM and podocytes layer).
 Molecular charge is also an important factor affecting glomerular localization:
 Cationic complexes-subepithelial deposition.
 Anionic complexes – subendothelial deposition.
 Neutral charge complexes – Mesangium
 Subendothelial deposits – causes inflammation because circulating leukocytes are easily
available.
 Subepithelial deposits – non inflammatory pathology.
 Trapping of circulating immune complexes can initiate further in situ complex formation.
 Other mechanisms of Antibody mediated injury- ANCA & AECA

AGAM PATHOLOGY
Cell Mediated Immunity in GN:
 Although initiation of glomerular injury is done by immune complexes progression and
propagation of inflammation is done by activated T cells and macrophages.
 GN in humans primarily from T cell activation is unclear.
 Various cells involved in glomerular injury are:
 Neutrophils & Monocytes: activation of complement system and release of proteases
and other ROS.
 Macrophages and T cells: release cytokines, chemokines and other pro –
inflammatory biological molecules.
 Mesangial cells: these cells release various growth factors like PDGF, VEGF, TGF-beta;
cytokines, ROS, NO.
 Epithelial Injury (Podocytopathy): seen in diabetic nephropathy and FSGN. It results in
proteinuria.
 Effacement, Vacuolization & detachment of cells from GBM.
 Mutations in slit diaphragm proteins causes hereditary nephrotic syndrome.

AGAM PATHOLOGY
5. POSTSTREPTOCOCCAL GLOMERULONEPHRITIS (PSGN)
 PSGN is a prototype of exogenous-antigen induced pattern of post infective
glomerulonephritis.
 It develops usually after 1-4 weeks after streptococcal infection of pharynx
(Streptococcus pharyngitis) or skin (S.impetigo).
 It is usually seen in children of 6 to 10 yrs. but adults can also be affected.
PATHOGENESIS:
 Caused by immune complexes containing streptococcal antigen and specific antibodies.
 Only some strains of group A beta-hemolytic streptococci are nephritogenic.
 Serotypes commonly involved are types 1, 4, 12, 49 (according M protein typing).
 The principal antigenic component responsible for PSGN is streptococcal pyogenic
exotoxin B (SpeB).
 Excessive activation and consumption of complement system proteins results in reduces
serum complement levels.
 Hump-like granular immune deposits in glomeruli are observed because of immune
complexes deposition.
 Initially immune complexes form hump-like deposits along the subendothelial wall, later
these complexes dissociate and migrate along the glomerular basement membrane
(GBM) and re-form on the subepithelial side.

Streptococcal infection (Pharyngitis/pyoderma)

Streptococcal proteinase exotoxin B

(SpeB)
Development of in-situ circulating immune complexes

Granular deposits in sub-endothelial and mesangial locations

Initiate an inflammatory reaction (local complement

activation, recruitment of neutrophils and macrophages)

Cationic antigens or dissociation of immune complexes into the outer aspect

Post-streptococcal glomerulonephritis

AGAM PATHOLOGY
HISTOLOGICAL FINDINGS:
 Enlarged and hypercellular glomeruli.
 Global and diffuse proliferation and leukocytic infiltration.
 Interstitial edema and inflammation, and red cell casts are seen.
 Immunofluorescence microscopy shows IgG and C3 granular deposits in the mesangium
and along GBM.
 Electron microscopic findings are ‘hump’ like immune complexes deposits on
subepithelial membrane.

CLINICAL FEATURES:
 Clinical presentation is as Nephritic syndrome:
 Oliguria
 Hematuria- smoky or cola colored urine
 Mild to moderate hypertension
 Mild proteinuria
 Dysmorphic red cells in urine.
 Typical presentation is of a young child, 1 to 2 weeks after recovery from sore throat.
 More than 95% eventually recover renal function with conservative therapy of
maintaining sodium and water balance.
 Some patients (less than 1%) develop Rapidly-progressive/Crescentic form of
glomerulonephritis.
 And remaining patients undergo slow progression into chronic glomerulonephritis.

LABARATORY FINDINGS:
 Elevation of anti-streptococcal antibody titers.
 Elevation of BUN.
 Decline in concentrations of serum C3 and other complement proteins.

AGAM PATHOLOGY
SHORT NOTES
1. PATHOGENESIS OF CARCINOMA KIDNEY
 Most renal carcinomas are sporadic.
 3p deletion
 Trisomy 7,16,17
 Mutated MET proto-oncogene
 Pediatric papillary RCC t(X:1)

 Autosomal dominant familial variant account for 4% of cases

Von Hippel-Lindau (VHL) syndrome
 Located on chromosome 3q
 VHL is a tumor suppressor gene that encodes part of a ubiquitin ligase complex
 Associated with both familial and sporadic form
 Most commonly associated with bilateral clear cell type of renal cell carcinoma

Hereditary leiomyomatosis and renal cell cancer syndrome

 Autosomal dominant disease
 It is due to mutation of FH gene (fumarate hydratase gene)
 It is characterized by cutaneous and uterine leiomyoma and metastatic type of
aggressive papillary carcinoma

Hereditary papillary carcinoma

 Autosomal dominant inheritance
 Due to mutation of MET proto-oncogene
 MET proto-oncogene encodes tyrosine kinase receptor for hepatocyte growth factor
(scatter factor)

Birt-Hogg-Dude syndrome
 Autosomal dominant inheritance pattern due to BHD gene mutation (this gene expresses
folliculin)
 It is most commonly associated with chromophobe type of renal cell carcinoma.

AGAM PATHOLOGY
2. RENAL CELL CARCINOMA
 Also known as hypernephroma or Gradwitz's tumors
 They are adenocarcinomas arising from tubular epithelium
 Commonly affects male of age group 50-70 years
Risk factors
 unopposed estrogen  tobacco
 exposure to asbestos  obesity
 Petroleum products and heavy metals.  hypertension

Clinical features
 Presents with classical triad of
 Hematuria (most common and earliest presentation)
 Abdominal mass
 Flank pain
 They are associated with following paraneoplastic syndromes
 Increased ESR (most common)
 Hypertension
 Hypercalcemia
 Polycythemia
 Amyloidosis (AA type)
 Nephrotic syndrome and fever
 Stauffer syndrome (non-metastatic hepatic dysfunction)
 Cushing syndrome
 Most Angio invasive cancer (more than hepatocellular carcinoma)
 Venous system involvement is seen in 10% of renal cell carcinoma
 Most common site of metastasis is lung

Morphology:
 Site: Upper pole
 Size: Varies.
 Outer surface: Bosselated
 Cut surface: Tumor looks yellow grey white and shows area of hemorrhage, necrosis
and cystic change.
 RCC has the tendency to invade renal vein.

AGAM PATHOLOGY
TYPES OF RENAL CELL CARCINOMA
Clear cell type
 Cell of origin – Proximal tubules
 Clinical features
 Most common type
 Solitary
 Unilateral
 Most commonly from upper pole
 Histology: Tumor cell with clear cytoplasm due to cytoplasmic vacuoles containing
glycogen and lipids.
 Cytogenetics
 Sporadic: 3p deletion (most common cytogenetic abnormality)
 Familial:
 VHL gene mutation
 VHL gene hypermethylation
 t(3:6),t(3:8),t(3:11)

Papillary/chromophilic
 Cell of origin –Proximal tubule
 Clinical features
 Multifocal and bilateral
 Most angioinvasive subtype
 MC renal cancer associated with dialysis associated cystic disease
 Histology: Papillary pattern with psammoma bodies
 Cytogenetics
 Sporadic: trisomy 7,16,17; pediatric papillary RCC t(X:1); mut. MET proto-oncogene
 Familial: trisomy 7; mutated /activated MET proto-oncogene

Chromophobe type
 Cell of origin – collecting duct (intercalated cells)
 Clinical feature – best prognosis
 Histology
 tumor cells are eosinophilic cytoplasm; perinuclear halo with plant like appearance
 electron microscopy shows numerous microvesicles (150-300nm)
 Cytogenetics: Loss of multiple chromosome; extreme hypodiploidy

AGAM PATHOLOGY
Bellini’s duct carcinoma
 Cell of origin – collecting duct cell in medulla
 Clinical feature – worse prognosis
 Histology – hobnail pattern and desmoplastic reaction
Xp11 translocation
 Clinical feature – rare tumor; young patient
 Histology – tumor cells have clear cytoplasm with papillary architecture
 Cytogenetics –TFE3 gene translocation on chromosome Xp11

3. DIFFERENCE BTW NEPHRITIC AND NEPHROTIC SYNDROME

Nephritic syndrome Nephrotic syndrome
PATHOPHYSIOLOGY Inflammation of glomeruli Increased permeability of glomeruli
Causes I. Primary glomerulonephritis I. Primary glomerulonephritis
1. Acute glomerulonephritis 1. Minimal change disease
2. Rapidly progressive 2. Membranous glomerulonephritis
glomerulonephritis 3. Focal segmental
3. Membranoproliferative glomerulosclerosis
glomerulonephritis II. Systemic diseases
II. Systemic diseases 1.SLE
1.SLE 2.Amyloidosis
2. Polyarteritis nodosa 3. Diabetes mellitus
3. Henoch-Schönlein purpura 4. Drugs, infections, malignancies
CLINICAL FEATURES
Proteinuria <3gm/day >3gm/day
Hypoalbuminemia Uncommon Present
Edema Due to ↓ osmotic pressure & Due to Na+ and water retention
Na+ and H2O retention
Hematuria Present , microscopic Absent
Hypertension Present Present in advanced cases
Hyperlipidemia Absent Present
Lipiduria Absent Present
Oliguria Present Present in advanced case
Hypercoagulability Absent Present

AGAM PATHOLOGY
4. NEPHROSCLEROSIS
BENIGN NEPHROSCLEROSIS
 Elderly patients with benign hypertension are most commonly affected
 Gross:
 Bilateral symmetrical contraction of kidney
 Diffuse granular surfaces due to scarring and contraction of individual glomeruli
(leather grain appearance)
 Microscopy:
 Atherosclerotic changes in large vessels
 Afferent arterioles are characteristically affected
 Hyaline arteriolosclerosis: homogenous eosinophilic hyaline material is deposited and
thickened the vessel wall
 Cystic medial necrosis is arcuate and interlobular arteries
 Proteinuria is mild
 Renal failure is rare
 Activity of RAAS is normal
MALIGNANT NEPHROSCLEROSIS
 Malignant nephrosclerosis is associated with accelerated hypertension
 Gross:
 Variable size of kidney
 Flea bitten kidney : characteristic pinpoint petechial hemorrhages on the surface of
kidney due to rupture of arterioles and capillaries
 Microscopy:
 Hyper plastic arteriopathy : concentric hyper plastic proliferation of smooth muscles
together with collagen will give appearance of onion skin lesion
 Fibrinoid necrosis : it involves arterioles with inflammation and thickening of vessel
wall (necrotizing arteriolitis)
 Glomerular thrombotic microangiopathy
 Renal failure is more common
 Proteinuria is marked
 Signs of malignant hypertension such as retinopathy encephalopathy is seen
 Activity of RAAS is increased.

AGAM PATHOLOGY
 5. CYSTIC LESIONS OF KIDNEY
 Hereditary, developmental and acquired disorders.
 Maybe congenital/acquired and neoplastic/non-neoplastic (mostly congenital and non-
neoplastic)
 Clinical presentation: Abdominal mass, Infection, Respiratory distress, Hemorrhage,
Neoplastic transformation

DISEASE PATHOLOGIC FEATURES CLINICAL FEATURES TYPICAL OUTCOME

Adult polycystic Large multicystic kidneys, Hematuria, UTI, Renal Chronic renal failure
kidney disease Liver cysts, Berry stones, Hypertension beginning at 40-60
aneurysms years
Childhood Enlarged, cystic kidneys at Hepatic fibrosis Variable, death in
polycystic kidney birth infancy or
disease childhood
Medullary sponge Medullary cysts on Hematuria, UTI, Benign
kidney excretory urography Recurrent renal stones
Familial juvenile Corticomedullary cysts, Salt wasting, Polyuria,
Progressive renal
nephronophthisis Shrunken kidneys Growth retardation, failure benign in
Anemia childhood
Adult-onset Corticomedullary cysts, Salt wasting, Polyuria
Chronic renal failure
medullary cystic Shrunken kidneys beginning in
disease adulthood
Multi-cystic renal Irregular kidneys with Association with other Renal failure if
dysplasia cysts of variable size renal anomalies bilateral, surgically
curable if unilateral
Acquired renal Cystic degeneration in end Hemorrhage,Neoplasia Dependence on
cystic disease stage kidney disease Erythrocytosis, dialysis
Simple cysts Single or multiple cysts in Microscopic hematuria Benign
normal sized kidneys

AGAM PATHOLOGY
 6. AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
 Multiple, expanding cysts on both kidneys
 Destroys the renal parenchyma and cause renal failure
Genetics:
Gene affected PKD1 PKD2
Located on chr. 1p13.3 4q 21
Protein encoded Polycystin-1 Polycystin-2
Located at Tubular epithelial cells - distal nephron All segments of renal tubules
Function of protein Cell-cell/cell-matrix interactions Ca2+ permeable cation channel
Pathogenesis: Mutations in Polycystin 1, 2 or fibrocystin

Altered mechanosensation by tubular cilia Altered Calcium flux

Altered tubular epithelial growth and differentiation

Abnormal extracellular matrix Cell proliferation Fluid secretion

Morphology: Cyst
 Gross:
 Bilaterally enlarged upto 4kg/kidney
 Cysts with a diameter of 3-4 cm filled with clear serous/turbid fluid.
 Microscopically:
 Variable lining epithelia
 Bowman’s capsule occasionally involved
Clinical features:
 Asymptomatic until renal insufficiency occurs
 Hemorrhage/dilation---cause pain
 Hematuria, polyuria, proteinuria, hypertension
 40% of cases have extra-renal congenital anomalies (like polycystic liver disease)
 20-25%-- mitral valve prolapse

AGAM PATHOLOGY
7. WILM’S TUMOR (NEPHROBLASTOMA)
 Embryonic tumor-derived from primitive renal epithelial/mesenchymal components
 Most common primary renal tumor of children (incidence being increased b/w 2-5 years)
Etiology and Pathogenesis:
 DEFECT of WT1 gene on chromosome 11p13 results in abnormal growth of metanephric
blastema without differentiation into normal tubules and glomeruli.
 Higher incidence: monozygotic twins,cases with family history
 The risk of Wilm’s tumor is increased in
 WAGR syndrome
 (Wilm’s tumor, Aniridia, Genital abnormalities, Mental retardation)
 Carry germline deletions of chromosome 11p13-which contains genes WT1 (Wilm’s
tumor associated gene) and PAX6 (aniridia)
 Denys-Drash syndrome: (mutation of WT1 gene) Due to common genetic mutation,
individuals with gonadal dysgenesis are at a higher risk.
 Beckwith-Wiedemann syndrome (WT2 gene imprinting abnormalities)
 Associated with other malignancies like retinoblastoma, neuroblastoma.
Morphology:
 Gross:
 Large, solitary, well-circumscribed mass.
 Usually unilateral
 On cut section- Soft, homogeneous, tan to gray with occasional foci of hemorrhage,
cysts and necrosis.
 Microscopically: Cell types seen:
 Blastemal- sheets of small round to oval blue cells with scanty cytoplasm
 Immature Stromal- undifferentiated fibroblast like spindle cell. (Sarcomatoid tumor
cell).
 Immature Epithelial-abortive tubules/glomeruli
 5% of tumors reveal anaplasia.
Clinical features:
 Large abdominal mass.
 Hematuria, pain in abdomen, intestinal obstruction, hypertension.
 Pulmonary metastases-seen in some cases.
 Increased risk of developing soft tissue sarcomas, leukemia, lymphomas and breast
cancers.

AGAM PATHOLOGY
8. ACUTE PYELONEPHRITIS
 It is a common inflammation of kidney and renal pelvis, caused by bacterial infections
 It is a manifestation of UTI
 Infections can be:
 Lower tract infection –cystitis, prostatitis and urethritis
 Upper tract infections- pyelonephritis
 or both
 Lower tract infections are mostly localized and do not spread to the kidney
Pathogenesis
 Causative agent-
 Enteric gram-negative bacilli:  Uncommon
 Escherichia coli (common)  Staphylococci
 Proteus  Enterobacter  Streptococcus
 Klebsiella  Pseudomonas
 Routes of infection;
 Ascending infection
 Hematogenous infection
 Adhesion of bacteria to the mucosal surface by fimbriae and colonization of distal
urethra
 Then they reach the urinary bladder by expansive growth of colonies (increased
during catheterization or cystoscopy)
 Mostly affect females due to
 Close proximity of urethra and rectum
 Short urethra
 Trauma to urethra during sexual intercourse
 Bladder urine is sterile due to
 Antimicrobial property of bladder mucosa
 Flushing mechanism
 Outflow obstruction (uterine prolapsed, prostatic hyperplasia) and bladder disfunction
lead to UTI
 Bacteria multiply inside the bladder, ascend through the ureter to infect renal pelvis and
parenchyma
 Incompetence of vesicourethral orifice- congenital or acquired (vesicourethral reflex)
also lead to ascending infection and residual urine

AGAM PATHOLOGY
 Intrarenal reflux also leads to parenchymal infection
 UTI increased in case of diabetes, neurogenic bladder and pregnancy
 Risk factors
 Diabetes  Intraparenchymal obstruction
 Neurogenic bladder  Immunosuppressive therapy
 Pregnancy  Immunodeficiency
 Renal surgery
 Hematogenous spread- occur by septicemia and infective endocarditis
Morphology
 Discrete yellowish raised abscesses on the renal surface –scattered or limited
 Microscopically liquefactive necrosis and abscess formation are seen
 Pus formation in tubules (large masses of neutrophils can be seen in interstitium –
white blood cast in urine)
 When obstruction is prominent it causes pyelonephritis
 Papillary necrosis –grey white-yellowish necrosis at the apices of pyramids
Clinical features Complications
 Pain at costovertebral angle  Papillary necrosis.
 Systemic-chills, fever, nausea, malaise  Pyonephrosis.
 Localized-dysuria, frequency, urgency  Perinephric abscess.
 Turbid urine-pyuria

9. CHRONIC PYELONEPHRITIS
 Grossly visible scarring and deformity of pelvicalyceal system

Types
 Chronic obstructive pyelonephritis
 Obstructive lesions lead to recurrent bout of renal inflammation
 It can be bilateral (congenital anomaly of urethra) (or)
 Unilateral (calculi, unilateral obstructive lesions of ureter)

 Chronic reflux associated pyelonephritis

 Superimposition of UTI on congenital vesicourethral reflux and intrarenal reflux
 It can be unilateral or bilateral

AGAM PATHOLOGY
Morphology
 Uneven scarring
 Scarring involve pelvis, calyces or both lead to calyceal deformity
 Interstitial fibrosis and inflammatory infiltrate
 Dilatation or contraction of tubules with colloid cast

Clinical features
 Late detection
 Asymmetrically contracted kidney with blunting or deformity of calyces
 Bilateral-hyposthenuria (polyuria and nocturia)
 Secondary glomerulosis (proteinuria)
 Chronic kidney disease
 Arteriosclerosis caused by associated hypertension

10. IMMUNE COMPLEX GLOMERULONEPHRITIS:

 Deposition of anti-bodies specific for fixed or planted antigens in the glomerulus leading
to glomerular injury is called Immune complex glomerulonephritis.
 Types of deposits based on Site of deposition- Mesangial deposits, Subendothelial
deposits & Subepithelial deposits.

Site and factor

 Molecular charge- Highly cationic- subepithelial location, highly anionic-subendothelial
region, neutral charge- accumulate in mesangium.
 Molecular size- medium size with slight excess antigen enter glomerular basement
membrane.
 Mechanisms of Antibody deposition- Local immune complexes & Circulating immune
complexes.

Electron microscope: shows immune complex as electron dense deposits in mesangium,

subendothelial, subepithelial, basement membrane, or more than one site

Immunofluorescent microscopy: Immune complex deposits as granular

immunofluorescence in either basement membrane or mesangium or in both.

AGAM PATHOLOGY
11. RENAL STONES
 They are found most commonly in the renal calyces and pelvis of kidney.
 Primary bladder stone- Develops in sterile urine and originates in kidney.
 Secondary bladder stone-Seen in infections and outflow obstruction.
Pathogenesis:
 Supersaturation of urine occurs due to increase in solubility of urine.
 Deficiency of inhibitors of crystal formation in urine enhances precipitation of crystals -
nephrocalcin, GAGs, pyrophosphate, citrate and osteopontin.
Clinical features of renal stones: Complications:
 Ulceration, bleeding  Hematuria
 Colicky pain.  Hydronephrosis
 Larger stones present with hematuria.  Pyelonephritis and Pyelonephrosis
 Predisposes to infection.  Squamous cell carcinoma.
TYPES OF RENAL STONES:
A. CALCIUM OXALATE STONES
 Majority (80%) of renal stones are composed of calcium and oxalate or phosphate.
 These are radio opaque.
 Etiology:
 Hypercalciuria without hypercalcemia- Hyperabsorption of calcium from intestine,
defective tubular reabsorption of calcium in renal tubules.
 Hypercalcemia with hypercalciuria- Hyperparathyroidism.
 Hyperoxaluria
 Idiopathic
 Morphology:
 It is hard and covered with sharp projections.
 May appear black due to hemorrhage from mucosa.
B. STRUVITE/TRIPLE STONES
 Composed of calcium phosphate often with magnesium and ammonium phosphate.
 Etiology: They usually develop after urinary tract infections by urease splitting bacteria
like Proteus leading to alkaline pH and precipitating magnesium, ammonium phosphate.
 Morphology:
 ‘Staghorn Calculus’ – Fills up pelvis and calyces to form a cast.
 Yellow white in colour.
 They are the largest stones.
 Radio opaque.

AGAM PATHOLOGY
 C. URIC ACID AND URATE STONES
 Seen in patients having hyperuricemia (Gout) or rapid cell turnover (leukemias).
 Could be idiopathic also.
 Acidic pH predisposes to these stones.
 Morphology:
 They are radiolucent.
 Smooth, hard and yellow.
 Usually multiple in number.
D. CYSTINE STONES
 Associated with cystinuria and occurs at a low urinary pH.
 Morphology:
 Small, round and smooth.
 Yellow and waxy.
 Radio opaque.
E. OTHER TYPES (e.g. hereditary xanthinuria developing xanthine stones).

12. ACUTE TUBULAR NECROSIS.

 It results from destruction of tubular epithelial cells.
 It is of two forms:
 Ischemic: Occurs due to hypoperfusion of kidneys resulting in focal damage to distal
parts of the convoluted tubules.
 Toxic: Occurs as a result of direct damage to tubules, more marked in proximal
portions, by ingestion, injection or inhalation of a number of toxic agents.

FEATURE ISHAEMIC ATN TOXIC ATN

Synonyms Tubulorrhectic ATN Nephrotoxic ATN
Frequency More common Less common
Gross Kidneys enlarged, swollen Similar to ischemic ATN.
appearance Cut section: cortex pale, medulla dark
Morphological Distal tubular damages prominent Proximal tubular damage prominent
features Focal tubular necrosis More diffuse tubular injury
Regenerating epithelium Regenerating epithelium
Casts: hyaline, pigment Tubular lamina with dystrophic
Myoglobin calcification.
Prognosis Worse Good

AGAM PATHOLOGY
PATHOGENESIS

AGAM PATHOLOGY
13. PROTEINS IN URINE (PROTEINURIA)
 Selective Proteinuria: In this type, only intermediate- sized proteins (such as albumin,
transferrin) leaks through the glomerulus.
 Nonselective Proteinuria: It is characterized by leakage of range of different proteins
including larger proteins (e.g., immunoglobulins) through the glomerulus

BENCE JONES PROTEINS:

 Bence Jones proteins are light chains of immunoglobulins, secreted in multiple myeloma.
 It may also be found in macroglobulinemia and lymphoma.
 Bence Jones proteins precipitate at temperature between 40°C and 60°C, and re-dissolve
near 100°C. It reappears on cooling to 40°–60°C.

MICROALBUMINURIA:
 Microalbuminuria is the presence of albumin in urine above the normal level but below
the detectable range of conventional methods.
 It is defined as the persistent elevation of the urinary albumin excretion of 20–200 mg/L
(or 20–200 micrograms/min) in an early morning urine sample.
 It indicates early and possibly reversible glomerular damage.
 Causes of microalbuminuria:
 Diabetes mellitus: In diabetic patients, presence of microalbuminuria is associated
with increased cardiovascular mortality and is a risk factor for renal mortality. Early
detection can predict the development of renal complications in diabetics.
 Essential hypertension: In hypertensive patients, microalbuminuria predicts
cardiovascular morbidity and mortality.

AGAM PATHOLOGY
SHORT ANSWERS:
1. MICROSCOPY OF CHRONIC PYELONEPHRITIS.
 Interstitium: shows chronic inflammatory infiltrate of lymphocytes and macrophages
and fibrosis.
 Tubules:
 Thyroidisation: dilated tubules with flattened epithelium filled with eosinophilic
hyaline material and resembles colloid containing thyroid follicles.
 Blood vessels: shows endarteritis obliterans.
 Glomeruli: periglomerular fibrosis.
 Calyces: shows fibrosis and chronic inflammatory infiltrate.

2. MYELOMA OF KIDNEY
 Malignant non renal tumors that affect the kidney
 Most common one is tubulointerstitial multiple myeloma (plasma cell neoplasm)
 Factors contributing to renal damage
 Bence jones proteinuria
 Ig light chain –toxic to epithelial cell
 Combine with urinary glycoprotein (Tamm – Horsfall protein –tubular cast) that obstruct
lumen
 Light chain cast neutrophil
 Amyloidosis(AL type)-formed by free light chain(lambda)
 Light chain deposition disease
 Hypercalcemia (nephrocalcinosis), hyperuricemia are also present

3. GRADING OF UROTHELIAL MALIGNANCY

 Stage 0: Carcinoma confined to the mucosa.
 Stage A: Carcinoma invades the lamina propria but not the muscularis.
 Stage B1: Carcinoma invades the superficial muscle layer.
 Stage B2: Carcinoma invades the deep muscle layer.
 Stage C: Carcinoma invades the perivesical tissue.
 Stage D1: Carcinoma shows regional metastases.
 Stage D2: Carcinoma shows distant metastases.

AGAM PATHOLOGY
4. PATHOGENESIS OF RENAL EDEMA
 Edema in case of renal failure is due to salt and water retention.
 Increased salt retention associated with water causes both increased hydrostatic
pressure and diminished vascular colloid osmotic pressure.
 Salt retention occurs whenever renal function is compromised, such as primary kidney
disorder and in cardiovascular disorder.
 Renal hypoperfusion is due to congestive heart failure which results in activation of RAAS
system.
 In early heart failure, it may be beneficial but as if heart failure worsens –cardiac output
diminishes, retained fluid merely increases hydrostatic pressure, leading to edema.
 Edema due to renal dysfunction often appears in loose connective tissue such as
PERIORBITAL EDEMA.

5. IMPORTANCE OF CASTS IN URINE

 The presence of casts in urine indicates following conditions:
 Hyaline casts- fever, dehydration, stress
 RBC casts—glomerulonephritis
 WBC casts – pyelonephritis
 Broad/waxy cast – chronic renal failure
 Lipid cast – nephrotic syndrome
 Muddy brown granular cast – acute tubular necrosis.

6. URINARY CASTS
 They are organized elements which are formed only in kidney and or indicator of renal
disease.
 They are formed due to solid solidification of Tamm Horsfall protein a glycoprotein which
is secreted in the distal convoluted tubules and collecting tubules.
 They are cylindrical in shape with parallel sides and rounded ends.
 CLASSIFICATION OF CASTS
 Matrix: Hyaline, waxy
 Cells: RBCs and it’s remnants, leucocytes, renal tubular epithelial cells, mixed cells.
 Inclusions: Granules (proteins, cell debris), fat globules (triglycerides, cholesterol
esters), hemosiderin granules.
 Pigments: Hemoglobin, myoglobin, bilirubin.

AGAM PATHOLOGY
7. CLEAR CELL CARCINOMA OF KIDNEY
 Clear cell carcinoma of kidney is a type of renal cell carcinoma.
 Cell of origin – proximal tubules
 Clinical features
 Most common type
 Solitary
 Unilateral
 Most commonly from upper pole
 Histology: Tumor cell with clear cytoplasm due to cytoplasmic vacuoles containing
glycogen and lipids.
 Cytogenetics:
 Sporadic: 3p deletion (most common cytogenetic abnormality) 95% are sporadic
 Familial:
 VHL gene mutation
 VHL gene hypermethylation
 t(3:6), t(3:8), t(3:11)

8. CONTRACTED GRANULAR KIDNEY

 It is the specific gross appearance seen in chronic glomerulonephritis, chronic
pyelonephritis and benign nephrosclerosis.
 Bilateral symmetrically involvement with fine, uniform and small, granular scars.
 Scars are V-shaped in benign nephrosclerosis whereas U-shaped in chronic
glomerulonephritis.

9. AUTOSOMAL RECESSIVE (CHILDHOOD) POLYCYSTIC KIDNEY DISEASE:

Types - Perinatal, Neonatal, Infantile, Juvenile
Genetics - Mutation of PKHD1 gene encoding fibrocystin
Morphology:
 Gross
 Enlarged kidney
 Smooth outer surface.
 Sponge- like appearance on cut section.
 Microscopically- Saccular dilation of collecting tubules.

AGAM PATHOLOGY
UPDATES
1. NEPHRITIC SYNDROME:
 Nephritic syndrome is the typical clinical presentation of most proliferative types of GN
such as postinfectious GN, crescentic GN, and proliferative lupus GN.
 The lesions that cause the nephritic syndrome have in common proliferation of the cells
within the glomeruli, often accompanied by an inflammatory leukocytic infiltrate.
 This inflammatory reaction severely injures the capillary walls, permitting blood to pass
into the urine and inducing hemodynamic changes that lead to a reduction in GFR.
 The reduced GFR is manifested clinically by oliguria, fluid retention, and azotemia.
 Hypertension probably is a result of both the fluid retention and renin release from the
ischemic kidneys.

2. GLOMERULONEPHRITIS
 Glomerulonephritis similar to PSGN occurs sporadically in association with other
infections, including those of
 Bacterial (staph. endocarditis, pneumococcal pneumonia & meningococcemia),
 Viral (hep B, hep C, mumps, HIV infection, varicella & infectious mononucleosis)
 Parasitic (malaria, toxoplasmosis) origin.
 In these settings, granular immunofluorescent deposits and subepithelial humps
characteristic of immune complex nephritis are also present

3. PLAR2:
 PLA2R - a membrane protein at the basal surface of the glomerular epithelial cell.
 Autoantibody binding to PLA2R is followed by complement activation and then shedding
of the immune aggregates from the cell surface.
 They form characteristic deposits of immune complexes along the subepithelial aspect of
the basement membrane
 Seen in Membranous Nephropathy

4. MEMBRANOUS NEPHROPATHY – ONE LINERS:

 Immunostains also reveal PLA2R or THSD7A glomerular positivity in the majority of
patients; however, a significant proportion of patients with secondary membranous
nephropathy can also be positive.
 As the disease advances, segmental sclerosis may occur; in the course of time, glomeruli
may become totally sclerosed.

AGAM PATHOLOGY
5. MALIGNANT HYPERTENSION:
 A small percentage of hypertensive persons (as many as 5%) show a rapidly rising blood
pressure that, if untreated, leads to death within 1 to 2 years.
 This form of hypertension, called malignant hypertension, is characterized by severe
pressure elevations (i.e., systolic pressure >200 mm Hg, diastolic pressure >120 mm Hg),
renal failure, and retinal hemorrhages and exudates, with or without papilledema
(swelling of the optic nerve that reflect increased intracranial pressures)

6. ONE LINERS
 Renal Papillary Adenoma are small tumors less than 1.5 cm in diameter.

7. NEW TOPIC
 Pg 934: Autosomal Dominant Tubulointerstitial Kidney Disease

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AGAM PATHOLOGY