The document provides a comprehensive overview of glomerulonephritis, including its definition, classification, pathogenesis, and morphology. It categorizes glomerular diseases into acute and chronic forms, detailing their causes and associated syndromes like nephrotic and nephritic syndromes. Additionally, it discusses the pathophysiology, complications, and various types of glomerular diseases, including their etiology and mechanisms.

1. Glomerulonephritis:
Definition, Classification,
Pathogenesis
and Morphology
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2. Normal Anatomy of Kidney
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3. 4/24/2022 3

4. Normal glomerulus
• Glomerulus has been cut through the
vascular pole which is seen at 6 o’clock.
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5. • Glomerular filtration membrane/barrier
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6. 4/24/2022 6

7. • Definition:
– Inflammation of glomeruli is called
glomerulonephritis.
– Glomerular diseases which do not have a cellular
inflammatory component are called
glomerulopathy.
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8. Classification of glomerulonephritis
A]. Acute glomerulonephritis
B]. Chronic glomerulonephritis
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9. Acute Glomerulonephritis
1. Acute Proliferative GN
(Poststreptococcal/Postinfectious GN)
2. Membranous glomerulopathy
3. Membranoproliferative GN
4. Minimal change disease
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10. 5. Focal Segmental Glomerulosclerosis
6. Rapidly Progressive GN (Crescentic GN)
7. HIV nephropathy
8. IgA nephropathy
9. Henoch-Schönlein Purpura
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11. • Chronic glomerulonephritis refers to
end-stage glomerular disease.
• It is of two types:
a). Chronic GN developing secondary to acute
glomerulonephritis
b). Chronic GN developing de novo:
- These cases develop without antecedent acute
glomerulonephritis.
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Chronic Glomerulonephritis

12. Causes of Chronic Glomerulonephritis
1. Membranous glomerulopathy,
2. Membranoproliferative glomerulonephritis,
3. IgA nephropathy,
4. Focal Segmental Glomerulosclerosis
5. Acute Poststreptococcal GN in adults
6. Crescentic glomerulonephritis
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13. Second method of Classification of Glomerular
Diseases
A]. Primary Glomerulopathies:
– Acute proliferative GN
– Rapidly progressive (crescentic) GN
– Membranous glomerulopathy
– Minimal-change disease
– Focal segmental glomerulosclerosis
– Membranoproliferative GN
– IgA nephropathy
– Chronic GN
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14. B]. Systemic Diseases with Glomerular
Involvement:
– Systemic lupus erythematosus
– Diabetes mellitus
– Amyloidosis
– Goodpasture syndrome
– Microscopic polyarteritis/polyangitis
– Wegener granulomatosis
– Henoch-Schönlein purpura
– Bacterial endocarditis
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15. Third method of classification of glomerular
diseases
• Glomerular diseases can also be classified in
the following way:
a). Glomerular diseases which cause nephrotic
syndrome
b). Glomerular diseases which cause nephritic
syndrome
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16. Etiology of Nephrotic Syndrome
A]. Primary causes:
a). Most common causes are:
1. Minimal change disease (MCD):
- most frequent cause of nephrotic syndrome in children.
2. Focal segmental glomerulosclerosis (FSGS):
- 20-30% cases of nephrotic syndrome
3. Membranous glomerulopathy (MGN)
b). Other causes are:
1. Membranoproliferative Glomerulonephritis (MPGN)
2. IgA Nephropathy
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17. B]. Secondary causes:
1. Diabetic nephropathy
2. Preeclampsia (new-onset hypertension and
proteinuria after 20 wk gestation)
3. Lupus nephritis
4. Hypertensive nephropathy due to malignant HTN
(hypertensive emergency)
5. Amyloidosis
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18. • Memory clue:
- Diseases which cause effacement of foot
processes of podocytes cause nephrotic
syndrome: MCD, MGN, Diabetic nephropathy
and FSGS.
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19. Etiology of Nephritic syndrome
1. Hereditary nephritis (Alport’s syndrome)
2. Ig A nephropathy
3. Rapidly Progressive Glomerulonephritis (RPGN)
4. Acute Proliferative Glomerulonephritis (APGN)
5. Lupus nephritis
• IgA nephropathy and Lupus nephritis also can
cause nephrotic syndrome and mixed
nephritic-nephrotic syndrome.
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HIRA Lal

20. Nephrotic syndrome
• Nephrotic syndrome is characterized by:
a). Heavy proteinuria (>3.5 gm/24 hours)
b). Hypoalbuminemia (<3.0 gm/dL)
c). Hyperlipidemia and lipiduria: fatty casts and oval fat
bodies are seen in urine.
e). Generalized edema: Severe generalized edema is called
anasarca.
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21. Pathophysiology of Nephrotic syndrome
• Following events occur sequentially:
1). Glomerular diseases
2). Heavy proteinuria
3). Hypoalbuminaemia
4). Compensatory increase in protein synthesis by
the liver including lipoproteins LDL and VLDL =
Hyperlipidemia.
5). Hyperlipidemia leads to loss of lipid in urine =
lipiduria.
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22. 6). Hypercoagulability:
• The causes of hypercoagulability are:
– Loss of antithrombin III
– Increased hepatic synthesis of clotting factors
– Hyperviscosity caused by hypovolemia.
7). Edema is due to a decrease in oncotic pressure
because of:
- Hypoalbuminaemia and
- Primary defect in sodium excretion.
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23. Complications of nephrotic syndrome
1. Thromboembolism especially renal vein
thrombosis and pulmonary embolism.
– Occurs in up to 5% of children and 40% of adults.
• The causes of hypercoagulability are:
– Loss of antithrombin III
– Increased hepatic synthesis of clotting factors
– Hyperviscosity caused by hypovolemia
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24. 2. Increased risk of infection:
- due to loss of immunoglobulins and complement
in urine.
3. Coronary artery disease in adults due to
hyperlipidemia.
4. Anemia due to loss of erythropoietin and
transferrin.
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25. • Components of nephrotic syndrome: a to d.
a). Heavy proteinuria: >3.5 gm/24 hours
b). Hypoalbuminemia (< 3.0 gm/dL)
c). Hyperlipidemia and lipiduria
d). Generalized edema
• Patients presenting with proteinuria without
other components of nephrotic syndrome:
– nephrotic-range proteinuria.
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26. Nephritic Syndrome
• Nephritic syndrome is characterized by the
presence of following features:
– Hematuria with dysmorphic RBCs and RBC casts in the urine.
– Proteinuria: <3.5 g/day (non nephrotic-range proteinuria)
– Edema
– Hypertension
– Uremia
– Azotemia
– Oliguria (urine output <400 mL/day)
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27. • Azotemia:
– elevation of blood urea nitrogen (BUN) (reference
range: 8-20 mg/dL) and/or
– serum creatinine (normal value: 0.6-1.2 mg/dL)
levels.
• Uremia:
– Azotemia plus clinical manifestations.
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28. • Hypertension in glomerular diseases is due to a
number of factors:
1. Activation of renin-angiotensin-aldosterone system
(RAS):
- Hypovolemia in nephritic syndrome activates renin-
angiotensin-aldosterone system.
2. Increased activity of RAS causes:
- Increased sodium reabsorption from collecting ducts and
thus sodium retention by aldosterone.
- Increased total peripheral resistance because of
vasoconstriction. Vasoconstriction is caused by
angiotensin.
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29. 3. Activation of sympathetic nervous system:
- Intrarenal ischemia also causes increased activity of
sympathetic nervous system leading to vasoconstriction.
4. Endothelial cell dysfunction (decreased NO activity)
leading to reduced vasodilation.
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30. Acute Proliferative (Poststreptococcal, Postinfectious) GN
• Streptococcal infections are associated with
overcrowding and poor hygiene.
• Etiology:
A]. Group A β-hemolytic streptococci:
- 90% cases are due to 12,4,1 serotypes.
- Infection occurs in the pharynx or skin (impetigo).
- Age group: 6 to 10 yrs, but adults may also get
affected.
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31. B]. Non-streptococcal postinfectious glomerulonephritis
(less common):
:Bacteria other than streptococci- staphylococcal
endocarditis, pneumococcal pneumonia, and
meningococcemia.
:Viral- hepatitis B and C, mumps, HIV, varicella
:Parasitic- malaria, toxoplasmosis
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32. Pathogenesis of APGN
APGN is an immune complex mediated disease
(type 3 hypersensitivity rxn):
1). First event is exposure to antigen of microbe:
APGN appears 1 to 4 wks after the infection.
2). Formation of immune complex:
- Antibodies are formed in blood against microbial
antigens which bind with antigens to form immune
complexes.
- They are carried by blood to kidneys and they are
deposited in the glomerular capillary wall.
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33. Pathogenesis of APGN continued
3). Classical pathway of complement system is
activated by the immune complexes:
- Complement products C3a and C5a are produced which
attract neutrophils and monocytes to the glomeruli.
- Inflammatory cells produce lysosomal enzymes and
reactive oxygen species which injure glomeruli.
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34. Membranous Glomerulopathy (MGN)
• Aka: Membranous nephropathy
• It is an immune complex mediated disease.
a). 75 % of cases are primary:
 Primary membranous glomerulopathy (idiopathic MG).
 It is an autoimmune disease.
 Antigen is present in podocytes. Major antigen is
phospholipase A2.
b). 25 % cases are secondary:
 Secondary membranous glomerulopathy
Associated with other diseases: presented in the following
slide.
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35. • Causes of secondary membranous glomerulopathy:
• These antigens are planted in the podocytes:
1. Drugs: NSAIDs, Gold, Penicillamine.
2. Underlying malignant tumors: Ca of lung and colon,
and melanoma.
3. Viral infections: Hepatitis B and C
4. Bacterial infections: syphilis, malaria
5. Autoimmune disease: 10% to 15% of
glomerulonephritis in SLE is of the membranous type.
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36. Pathogenesis of Primary MGN
Primary MGN is an autoimmune disease.
1). Formation of autoantibodies (IgG4) to an antigen
in the visceral epithelial cells (podocytes):
- phospholipase A2 receptor is the most common
antigen.
2). Immune complex (antibody+antigen) forms
in-situ which activates the lectin pathway of
complement system.
- IgG4 subtype, that is formed in this disease, cannot
activate classical pathway of complement system.
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37. 3). Membrane attack complex (C5b-C9) is the
product of complement activation:
 It activates glomerular epithelial and mesangial
cells.
The cells produce proteases and ROS, which injure
GFM.
• Inflammatory cells are scant in the glomeruli
because C3a and C5a do not have a role in the
pathogenesis.
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38. Pathogenesis of Secondary Membranous
Glomerulopathy continued
• Antibodies are formed against microbes, drugs
or neoplastic cells.
• Antibodies bind with antigen and immune
complexes are formed.
• Immune complexes activate classical pathway
of complement system.
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39. Membranoproliferative Glomerulonephritis
(MPGN)
Synonym: mesangiocapillary glomerulonephritis
It can be primary or secondary.
Primary MPGN is of two types:
- Type 1 and Type 2
- Now it is thought that type 1 and type 2 are different
disease processes.
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40. Pathogenesis of type 1 MPGN
1. Antigens: not known (idiopathic).
2. Immune complexes (antibodies+ antigens)
are deposited in the glomerular capillary wall=
Type 3 hypersensitivity rxn.
3. Activation of Classical Pathway of
Complement system and inflammation by C3a
and C5a fragments.
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41. Pathogenesis of type 2 MPGN
1. Type 2 MPGN= dense deposit disease.
2. It is now kept under “C3 glomerulopathy”
3. Activation of alternative pathway of complement
system. Inciting antigen: unknown.
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42. 4. Patients have an autoantibody (C3 nephritic
factor) which binds with C3 convertase and
stabilizes it; that means it can not be
degraded.
 Persistent generation of C3a and C5a occurs
because of persistent activation of C3 by C3
convertase.
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43. Secondary MPGN
• Pathogenesis is similar to type I.
• Arises in the following settings:
Chronic infections: HIV, hepatitis B and C infection,
chronic visceral abscesses.
Autoimmune disease: SLE
Malignant diseases: CLL and lymphoma
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44. Minimal-Change Disease (MCD)
• Synonym: lipoid nephrosis
• More common in children (2 to 6 yrs).
• Sometimes follows a respiratory infection or
immunization.
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45. Pathogenesis of MCD
• Exact mechanism is not clearly known.
• Two hypotheses are as follows:
a). Loss of charge-dependent barrier function
of glomerular filtration membrane:
 It occurs because some kind of immune
dysfunction produces loss of glomerular
polyanions.
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46. Pathogenesis of MCD continued
b). Loss of size-dependent barrier function of GFM
occurs because of mutations in structural proteins,
which are localized in the filtration slits.
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47. Focal Segmental Glomerulosclerosis (FSGS)
• FSGS occurs in the following settings:
1. As a primary disease (Idiopathic FSGS): no
associated systemic diseases.
2. Secondary to other diseases (Secondary FSGS): HIV
infection, sickle-cell disease and massive obesity.
3. As an adaptive response to loss of renal tissue in
other renal disorders (hypertensive nephropathy,
unilateral renal agenesis).
4. Mutations in genes that encode proteins of
filtration slits.
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48. • Pathogenesis is similar to that of MCD.
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49. Rapidly progressive GN (Crescentic GN)
 Does not denote a specific disease process.
 Is a syndrome associated with severe
glomerular injury because of other glomerular
diseases.
 Rapid and progressive loss of renal function
and death from RF can occur within weeks to
months.
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50. Classification of Causes of RPGN
A). Type 1: cause is anti-GBM antibody
- Renal limited and
- Good Pasture Syndrome
B). Type 2: caused by deposition of ICs in the
glomeruli:
 APGN
 Lupus nephritis
 Henoch-Schönlein purpura
 IgA nephropathy
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51. C). Type 3: vasculitic diseases
- Wegener granulomatosis
- Microscopic polyangitis
In 50% cases, the disorder is idiopathic: cause is
not known.
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52. HIV Nephropathy
• HIV infection can cause:
- Postinfectious glomerulonephritis
- Secondary MPGN
- FSGS
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53. Ig A Nephropathy
• Synonym: Berger disease.
• It was first described by Berger and Hinglais in
1968.
• Most common type of glomerulonephritis
worldwide.
• It is an autoimmune disease.
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54. • Ig A:
– two subclasses: Ig A1 and Ig A2
• Only Ig A1 can cause nephropathy.
• Some experts think that IgA nephropathy is a
localized form of Henoch Schonlein Purpura.
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55. Pathogenesis of IgA Nephropathy
a). IgA1 is abnormally glycosylated (it is galactose-deficient) in
this disease.
b). The abnormal Ig A1 induces formation of antibody (IgG)
against it.
- Immune complexes containing Ig A1 and IgG are
deposited in the mesangium of glomerulus.
c). Immune complexes activate mesangial cells to proliferate
and produce mesangial matrix, growth factors and
cytokines. Cytokines recruit inflammatory cells.
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56. c). ICs also activate alternative pathway of
complement system and hence the presence
of C3 and the absence of C1q and C4 in
glomeruli are typical of this disorder.
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57. Henoch-Schönlein Purpura
• It is an acute IgA–mediated disorder.
• Generalized vasculitis involving the small vessels
of:
– Skin, GI tract, Kidneys,
– Joints, and,
– rarely, lungs and CNS.
• Most common in children 3 to 8 years old, but it
also occurs in adults, in whom the renal
manifestations are usually more severe.
• Onset often follows an URTI.
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58. • Pathogenesis same as in IgA nephropathy.
• IgA nephropathy and Henoch-Schönlein
purpura are thought to be manifestations of
the same disease.
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59. Pathogenesis of Glomerulonephritis in a nutshell
S.N. Type of GN
Pathogenesis
1. APGN - Antigen (Ag): microbe (most common is Streptococcus pyogenes).
- Antibody forms and binds with Ag (Immune complex formation).
- Immune complex activates classical complement pathway.
- C3a, C5a recruit inflammatory cells. Glomerular injury occurs by
inflammatory mediators.
2. Primary MGN - Antigen is in podocytes. IgG4 antibody is formed.
- Immune complex activates lectin complement pathway.
- C5b-C9 activates glomerular epith. cells and mesangial cells which
produce proteases and oxygen species.
3. Type 1 Primary
MPGN
As in APGN.
4. Type 2 Primary
MPGN
- Activation of alternative complement pathway.
- C3 nephritic factor binds with C3 convertase and persistent
activation of C3 by C3 convertase occurs.
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60. Pathogenesis of Glomerulonephritis in a nutshell
SN Type of GN Pathogenesis
6. Secondary
MPGN
Same as in APGN
7. MCD a. Loss of charge-dependent barrier function of glomerulus
b. Loss of size-dependent barrier function of glomerulus
8. FSGS Same as in Minimal-change disease
9. Ig A
Nephropathy
- Deposition of immune complex containing Ig A1+antibody in
the mesangium which induce proliferation of mesangial cells
and secretion of growth factor and cytokines. Mesangial matrix
expansion and inflammation occur.
- Alternative pathway of complement system also activated.
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61. Morphological features of Glomerulonephritis
Acute postinfectious Glomerulonephritis:
 enlarged, diffusely hypercellular glomeruli.
Hypercellularity is caused by:
1. Inflammatory cells: neutrophils and monocytes;
2. Proliferation of endothelial and mesangial cells;
and
3. In severe cases crescent formation occurs.
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62. Morphology of APGN continued
4. Swelling of endothelial cells.
5. Combination of
proliferation, swelling, and
leukocyte infiltration
obliterates the capillary
lumens.
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63. Immunofluorescence microscopic features in APGN
Deposits of IgG, IgM, C1, C4 and C3 are found
in:
Deposits are mainly in subepithelial location in the
form of humps.
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64. Subepithelial humps
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65. Immunofluorescence microscopic picture of
APGN
Deposits are seen as bright
green fluorescence in a
granular, bumpy pattern.
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66. Electron microscopic picture of APGN
Subepithelial location
of deposits, often
having the appearance
of “humps”
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67. Morphology of MGN
• Uniform, diffuse filtration membrane thickening
due to:
a). Subepithelial deposits of immune complexes:
- Deposits between BM and visceral epithelium.
b). Diffusely thickened GBM: subepithelial immune deposits
stimulate glomerular epithelial cells to secrete basement
membrane material.
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68. Electron microscopic features of MGN
GBM spikes are present:
The spikes represent intervening matrix of
basement membrane between the subepithelial
deposits (spike and dome pattern).
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69. • Foot processes of podocytes are effaced in
MGN.
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70. 4/24/2022 70

71. Immunofluorescence microscopic features in
Primary Membranous Glomerulopathy
• Deposits of IgG4 and C3
appear in a diffuse
granular pattern by
immunofluorescence.
- C1 and C4 are absent.
Presence of C1 and C4
indicate secondary MGN.
4/24/2022 71

72. Immunofluorescence microscopic features in
Secondary Membranous Glomerulopathy
• Deposits of IgG, C1, C4
and C3 appear in a
diffuse granular pattern
by
immunofluorescence.
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73. Minimal-change disease
• Glomeruli are normal by light microscopy.
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74. EM features in MCD
• The only lesion is diffuse effacement of foot
processes of visceral epithelial cells.
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75. Morphology of MCD
• Effacement of foot processes is d/t flattening,
retraction and swelling of the processes.
– It is also seen in membranous glomerulopathy, FSGS
and diabetic nephropathy.
• Diagnosis of MCD = normal glomeruli by light
microscopy + effacement of foot proceses.
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76. 4/24/2022 76

77. Morphology in MPGN
A]. Light microscopic features:
• By light microscopy, both types of MPGN are
similar.
1. Glomeruli are large and hypercellular.
• Hypercellularity is produced by:
- Proliferation of mesangial cells and endothelial cells.
- Infiltration of glomerulus by leukocytes.
2. Expansion of mesangial matrix.
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78. Morphology in MPGN continued
3. Lobular accentuation:
 Glomeruli have an accentuated “lobular”
appearance due to proliferating mesangial cells and
increased mesangial matrix.
4/24/2022 78

79. Morphology in MPGN continued
4. Crescents are present in
many cases.
– These are made up of
proliferating cells.
4/24/2022 79

80. Morphologic features specific to Type 1 MPGN
5. GBM is thickened in type I MPGN.
• Glomerular capillary wall often shows a
“double-contour” or “tram-track” appearance,
especially evident in silver or PAS stains.
4/24/2022 80

81. • Tram-tracking is caused by “duplication” of the
basement membrane (also commonly referred
to as splitting), b/o new basement membrane
synthesis in response to subendothelial
deposits of immune complexes.
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82. • Tram in Oslo • Tram track in Belgium
4/24/2022 82

83. 4/24/2022 83

84. EM features in MPGN
• Type 1 and type 2 MPGN differ in their ultrastructural
features.
A]. Type 1 MPGN:
- Presence of discrete subendothelial electron-dense
deposits.
- Tram tracking of GBM
4/24/2022 84

85. • Interposition of mesangial cytoplasm occurs
into the split GBM.
4/24/2022 85

86. 4/24/2022 86

87. B]. Type 2 MPGN (Dense
Deposit Disease):
- ribbon-like electron-dense
deposition of dense
material of unknown
composition in the GBM.
4/24/2022 87

88. Immunofluorescence microscopy in
MPGN
• Type 1 MPGN:
– Classical Pathway Complement components C3, C1
and C4 and Ig G are deposited in a granular pattern.
• Type 2 MPGN:
- C3 is present in linear or granular pattern but classical
pathway complement components (C1, C4) and Ig G
absent. It indicates alternative complement pathway
activation.
- C3 is also present in the mesangium in characteristic
circular aggregates (mesangial rings).
4/24/2022

89. • Mesangial rings in type II MPGN
4/24/2022 89

90. Light microscopic features in FSGS
In this disease:
There is sclerosis of <50%
glomeruli (thus, it is focal)
and in the affected
glomeruli, only a portion
of the capillary tuft is
involved (thus, it is segmental).
4/24/2022 90

91. • In the focus of sclerosis, there is:
- collapse of capillary loops,
- increase in mesangial matrix, and
- deposition of plasma proteins along the capillary wall
(hyalinosis)
- presence of lipid droplets and foam cells.
4/24/2022 91

92. • EM features in FSGS:
• In both sclerotic and nonsclerotic areas:
- There is diffuse effacement of foot processes of
podocytes.
• IF microscopic features in FSGS:
– IgM and C3 may be present in the sclerotic areas
and/or in the mesangium.
– These deposits neither represent immune
complexes nor are pathogenic.
4/24/2022 92

93. Morphology of glomerulus in IgA nephropathy
Light microscopy:
• Morphology is variable:
– Glomeruli may appear normal.
– Inflammation may be present in only
a segment of some glomeruli (focal
segmental inflammation).
– Mesangial cells may be increased.
– Widening of mesangium may be seen
due to increased synthesis of
mesangial matrix.
4/24/2022 93

94. IF microscopic features
• C3, IgA1 and IgG are
present in the mesangial
deposits, but C1 and C4
are absent.
4/24/2022 94

95. Electron microscopic features of Ig A
Nephropathy
• Electron-dense deposits in the mesangium
4/24/2022 95

96. Light microscopic features of glomerular diseases in a
nutshell
S.N. Type of GN Light microscopic changes in the glomerulus
1. APGN • Enlarged, diffusely hypercellular glomeruli
(inflammatory cells, mesangial cells and endothelial cells)
• Obliteration of capillary lumen
2. MGN  Diffuse filtration membrane thickening
3. MCD  Glomeruli appear normal by light microscopy.
4. MPGN  Glomeruli are large and hypercellular ( inflammatory cells,
mesangial cells and endothelial cells).
 Increased mesangial matrix
 Lobular accentuation
4/24/2022 96

97. Light microscopic features of glomerular diseases in a nutshell
continued
S.N. Type of Glomerulonephritis Light microscopic changes in the glomerulus
5. FSGS  Focal and segmental sclerosis of glomeruli
6. Ig A nephropathy  Expansion of mesangial matrix
 Proliferation of endothelial and mesangial cells
4/24/2022 97

98. Electron microscopic features of glomerulonephritis in a
nutshell
S.N. Type of Glomerulonephritis Electron microscopic features
1. APGN  Subepithelial deposition of immune complex in the form
of humps
2. MGN  Discrete subepithelial deposition of immune complex
 GBM spikes
 Effacement of foot processes of podocytes
3. MCD o Effacement of foot processes of podocytes
3. Type 1 MPGN  Discrete subendothelial electron-dense deposits
 Tram-track appearance of GBM
4. Type 2 MPGN • Ribbon like electron-dense deposit in the GBM
4/24/2022 98

99. Electron microscopic features of glomerulonephritis in a
nutshell continued
S.N. Type of GN Electron microscopic features
5. Ig A nephropathy Electron-dense deposits in the mesangium
6. FSGS Effacement of foot processes of podocytes
4/24/2022 99

100. Immunofluorescence microscopic features of
glomerulonephritis in a nutshell
S.N. Type of GN Immunofluorescence microscopic features
1. APGN Deposits are seen as bright green fluorescence in a granular, bumpy
pattern. C1, C4, C3 (classic pathway complement system products)
and Ig G present.
2. Primary MGN Deposits of IgG and complement C5b-C9 appear in a diffuse granular
pattern
3. Secondary MGN Deposits having C1 and C4 indicate secondary MGN.
4. Type 1 MPGN Deposits contain same components as in APGN.
5. Type 2 MPGN C3 present in linear or granular pattern but classical pathway
components and Ig G absent.
C3 present in mesangial rings.
4/24/2022 100

101. Immunofluorescence microscopic features of
glomerulonephritis in a nutshell continued
S.N. Type of GN Immunofluorescence microscopic features
6. Ig A Nephropathy Immune complex deposit containing Ig A1 and C3 in the
mesangium.
Classical pathway components not present.
7. FSGS IgM and C3 may be present in the sclerotic areas and/or in
the mesangium.
Classical pathway components not present.
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102. Type 3 hypersensitivity
reaction (immune complex
diseases)
1. APGN
2. MGN
3. Type 1 MPGN
4. Secondary MPGN
5. IgA nephropathy
Activation of alternative
complement pathway
1. Type 2 MPGN
2. Ig A nephropathy
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• Classical pathway of
complement activation:
1. APGN
2. Type 1 MPGN
3. Secondary MPGN
• Lectin pathway of complement
activation
- Primary MGN

103. Effacement of foot processes of podocytes
1. Minimal-change disease
2. Focal segmental glomerulosclerosis
3. Membranous glomerulopathy
4. Diabetic nephropathy
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104. Subepithelial deposits
1. Acute Proliferative
Glomerulonephritis
2. Membranous
glomerulopathy
1. Type 1 MPGN
Subendothelial deposits
Deposits in the GBM
1. Type 2 MPGN
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105. Morphology in RPGN
• Kidneys are enlarged and pale.
• Petechial hemorrhages on the cortical
surfaces.
• Crescents are formed by:
– Parietal epithelial cells and
– Inflammatory cells in the bowman’s space
(monocytes, macrophages, neutrophils,
lymphocytes).
– Fibrin strands are frequently prominent between
the cellular layers in the crescents.
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106. Crescents
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107. Morphology in RPGN contd.
• Crescents eventually obliterate Bowman space
and compress the glomerular tuft.
• Electron microscopy may show ruptures in the
GBM, the severe injury that allows leukocytes,
proteins, and inflammatory mediators to reach
the urinary space, where they trigger the
crescent formation.
• In time, most crescents undergo sclerosis.
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108. Good Pasture Syndrome (Anti-GBM antibody disease)
• It is an autoimmune disease in which
autoantibodies are formed against antigen located
in the glomerular basement membrane and
alveolar basement membrane.
• Goodpasture syndrome most often manifests
as diffuse alveolar hemorrhage and
glomerulonephritis together.
– But it can occasionally cause glomerulonephritis (10 to
20%) or pulmonary disease (10%) alone.
– M > F.
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109. • Renal failure can occur in days: rapidly
progressive glomerulonephritis.
– Patient present with hematuria and other features of
renal failure.
• Commonly the first lung symptoms develop days,
weeks or months before kidney damage becomes
evident. :
– Clinical manifestations vary from dry cough and minor
dyspnea to severe lung hemorrhage.
– Hemoptysis is a useful presenting symptom.
• Anti-GBM antibody-mediated disease
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110. Pathogenesis of GPS
• Classical pathway of complement system is
activated by the immune complexes.
• Complement fragments C3a and C5a recruit
inflammatory cells to the glomerulus.
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111. • People with HLA-DRB1 antigen are found to be
genetically susceptible to develop the disease.
• There is negative association with HLA-DR7.
(Absence of this antigen is protective.)
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112. • Light microscopy:
– Crescents are seen in the glomeruli.
– Inflammatory cells infiltration
– Proliferation of mesangial cells and endothelial
cells.
• Immunofluorescence microscopy:
– The disease is characterized by linear deposits of
IgG, C1, C4 and C3 in the GBM.
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116. • Thank You !!
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117. Glomerular filtration membrane:
- Is highly permeable to water.
- Permeability of solute is size and charge-dependent:
larger, the less permeable and the more cationic, the more
permeable.
- So, the membrane prevents the passage of large
and/or negatively charged molecules (anionic
molecules), such as albumin. This barrier is called
glomerular filtration barrier.
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118. Factors responsible for glomerular filtration
barrier
1). Negatively charged molecules(proteoglycans of GBM and
sialoglycoproteins of epithelial and endothelial cell
membrane)are responsible for charge-dependent glomerular
filtration barrier function of glomerular filtration membrane.
2). Filtration slits and the proteins in the slits are responsible for
size-dependent as well as charge-dependent glomerular
filtration barrier function.
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119. • Entire glomerular tuft is
supported by mesangial
cells and mesangial
matrix lying between
the capillaries.
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120. • Mesangial cells:
- are contractile and phagocytic
- are capable of proliferation,
- can lay down both matrix and collagen
- can secrete several biologically active mediators.
Normal mesangium contains about 2 to 4
mesangial cells.
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121. • About 15% of
glomerular filtration
occurs through the
mesangium, with the
remainder through the
fenestrated
endothelium.
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122. Composition of Urine
• water 95%
• urea
• chloride
• sodium
• potassium
• creatinine
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123. • Protein and glucose are not present in urine
because of glomerular filtration barrier.
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124. Normal glomerulus
• Glomerular capillary loops thin and delicate.
• Endothelial and mesangial cells normal in number
• Surrounding tubules normal
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125. Normal glomerulus stained with PAS stain
• Basement membranes of glomerular capillary loops and tubular
epithelium highlighted.
• Capillary loops of this normal glomerulus are well-defined and thin.
• Endothelial cells are seen in capillary loops.
• Mesangial regions are of normal size.
• Podocytes along visceral epithelial surface. Bowman's space is seen along
with parietal epithelial cells.
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