Glomerulus and nephrotic & nephritic syndrome

Presented By Presented By Prof. Dr.Prof. Dr.

Nabil Tadros MikhailNabil Tadros Mikhail MBBS, MS Pathol., PhD Pathol.MBBS, MS Pathol., PhD Pathol.

Prof. of PathologyProf. of Pathology Alexandria University - EgyptAlexandria University - Egypt

Consultant & Chief PathologistConsultant & Chief Pathologist King Fahad Central Hospital King Fahad Central Hospital

Gizan - KSAGizan - KSA

Kidney diseases Glomerulonephritis , nephritic & nephrotic syndromes

The kidney can be divided into The kidney can be divided into

fourfour morphologic components morphologic components, ,

1.1. Glomeruli Glomeruli

2.2. Tubules Tubules

3.3. InterstitiumInterstitium

4.4. Blood vesselsBlood vessels. .

The kidney can be divided into The kidney can be divided into

fourfour morphologic components morphologic components, ,

1.1. Glomeruli Glomeruli

2.2. Tubules Tubules

3.3. InterstitiumInterstitium

4.4. Blood vesselsBlood vessels. .

Left: General organization of the kidney.

Right: Parts of a juxtamedullary nephron and its collecting duct and tubule

Portal circulation of the kidney 2 arterial capillaries

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The small spaces between adjacent processes constitute the filtration slits

subendothelium

subepithelium

intramembranous

Glomerular diseases are oftenGlomerular diseases are often immunologically mediatedimmunologically mediated

Whereas tubular and interstitium Whereas tubular and interstitium are more likely caused byare more likely caused by

toxic or infectious agentstoxic or infectious agents

Glomerular diseases are oftenGlomerular diseases are often immunologically mediatedimmunologically mediated

Whereas tubular and interstitium Whereas tubular and interstitium are more likely caused byare more likely caused by

toxic or infectious agentstoxic or infectious agents

Damage to one component almost Damage to one component almost always secondarily affect others. always secondarily affect others.

1.1. Severe Severe damage to glomerulidamage to glomeruli affect affect peritubular blood flowperitubular blood flow, ,

2.2. Tubular destructionTubular destruction, by increasing , by increasing intraglomerular pressure may induce intraglomerular pressure may induce glomerular atrophyglomerular atrophy. .

3.3. All forms of chronic renal disease will All forms of chronic renal disease will ultimately ultimately destroy all kidney componentsdestroy all kidney components and and lead to CRFlead to CRF..

Endless triangle

Glomerular diseasesGlomerular diseases

Glomerular diseases are a major problem in Glomerular diseases are a major problem in nephrology, nephrology,

Chronic glomerulonephritis (GN) is one of Chronic glomerulonephritis (GN) is one of the most common cause of CRF in humanthe most common cause of CRF in human..




Glomerular structureGlomerular structure

Glomerular structureGlomerular structure

The glomerulus consists of a network The glomerulus consists of a network of capillaries invested by epithelium. of capillaries invested by epithelium.

Structure of glomerular wallStructure of glomerular wall

The glomerular capillary wall is the filtering The glomerular capillary wall is the filtering area area

Consists of Consists of four basic structurefour basic structure::1.1. Thin layer of Thin layer of fenestrated endothelial cellsfenestrated endothelial cells..

2.2. Glomerular basement membraneGlomerular basement membrane (GBM) (GBM)::

3.3. Visceral epitheliumVisceral epithelium: (podocytes): (podocytes)

4.4. Mesangial cellsMesangial cells and and mesangial matrixmesangial matrix::


1- Thin layer of fenestrated 1- Thin layer of fenestrated endothelial cellsendothelial cells..

2- 2- Glomerular basement membrane (GBM)Glomerular basement membrane (GBM)::

It consists of It consists of

1.1. Collagen Collagen

2.2. Laminin Laminin

3.3. Fibronectin Fibronectin

4.4. Other proteins.Other proteins.


3- Visceral epithelium: (podocytes)3- Visceral epithelium: (podocytes)

It shows a characteristic foot processes It shows a characteristic foot processes (pedicles) (pedicles) embedded and adherent to GBM.embedded and adherent to GBM.

These foot processes are These foot processes are separated by separated by 20-30 nm filtration slit20-30 nm filtration slit which are bridged by a which are bridged by a thin diaphragmthin diaphragm

composed of nephrin molecules.composed of nephrin molecules.


3- Visceral epithelium: (podocytes)3- Visceral epithelium: (podocytes)

Visceral epithelium is critical to maintain Visceral epithelium is critical to maintain glomerular barrier functionglomerular barrier function..

It is the cell type that is largely responsible It is the cell type that is largely responsible for for synthesis of GBMsynthesis of GBM..


4- Mesangial cells and mesangial matrix4- Mesangial cells and mesangial matrix: : It serve as a It serve as a support of glomerular tuftsupport of glomerular tuft. . These cells is capable for These cells is capable for proliferation.proliferation. The whole glomerulus is surrounded by The whole glomerulus is surrounded by

parietal epitheliumparietal epithelium, which lines the , which lines the bowman’s space (urinary space),bowman’s space (urinary space), the cavity the cavity in which plasma filtrate first collect.in which plasma filtrate first collect.

15% of glomerular filtration15% of glomerular filtration

through the mesangiumthrough the mesangium,,

85% of glomerular filtration85% of glomerular filtration

through the fenestrated epitheliumthrough the fenestrated epithelium. .

PAS to highlight basement membranes. PAS to highlight basement membranes. The capillary loops of the glomerulus are well-defined and thin.The capillary loops of the glomerulus are well-defined and thin.

Glomerular barrier functionGlomerular barrier function

The major characteristic of glomerular The major characteristic of glomerular filtration are filtration are

1.1. High permeability to water and small High permeability to water and small moleculesmolecules

2.2. Almost Almost impermeableimpermeable to molecules of the to molecules of the

size of albuminsize of albumin (70KD). (70KD).

Glomerular barrier functionGlomerular barrier function

The latter characteristic is called The latter characteristic is called glomerular barrier functionglomerular barrier function, ,

Discriminates among protein depending on their sizeDiscriminates among protein depending on their size

(the larger, the less permeable). (the larger, the less permeable). Also Also the charge affect the permeabilitythe charge affect the permeability

(The more cationic the more permeable).(The more cationic the more permeable).


Glomerular diseasesGlomerular diseases Glomerular diseases may be Glomerular diseases may be Primary Primary ,where the kidney is the main or ,where the kidney is the main or

the only organ affected. the only organ affected. Secondary Secondary to other disease as to other disease as

1.1. SLE, SLE,

2.2. DM, DM,

3.3. Amyloidosis. ,Amyloidosis. ,

4.4. Polyarteritis nodosaPolyarteritis nodosa

5.5. others.others.

Here amyloid deposits are seen in glomeruli at the left and arteries at the right.Here amyloid deposits are seen in glomeruli at the left and arteries at the right.

Amyloidosis may beAmyloidosis may be

"AL""AL" type in patients with plasma cell type in patients with plasma cell dyscrasias (multiple myeloma) in which the dyscrasias (multiple myeloma) in which the amyloid is associated with excess amyloid is associated with excess immunoglobulin immunoglobulin light chain productionlight chain production, ,

"AA""AA" type or type or "amyloid associated""amyloid associated" in which in which the cause is often chronic inflammatory the cause is often chronic inflammatory

diseasesdiseases..

Pathogenesis of glomerular diseasesPathogenesis of glomerular diseases

Immune mechanisms underlie most cases Immune mechanisms underlie most cases of primary glomerular diseases .of primary glomerular diseases .

It may be It may be

1.1. Antibody mediatedAntibody mediated

2.2. Cell mediatedCell mediated..


1- Antibody mediated glomerular injury:1- Antibody mediated glomerular injury:


1- Antibody mediated glomerular injury:1- Antibody mediated glomerular injury:

Two forms are recognized:Two forms are recognized: A- Injury resulting from A- Injury resulting from

deposition of circulating immune complexes. (IC)deposition of circulating immune complexes. (IC) B- Injury by B- Injury by antibody reacting in situ within the glomerulus antibody reacting in situ within the glomerulus

(antiglomerular basement membrane antibodies) & (the Heymann’s model)(antiglomerular basement membrane antibodies) & (the Heymann’s model)

Immunofluorescence microscopy patternsImmunofluorescence microscopy patterns

Granular Linear

A- Circulating immune A- Circulating immune complexescomplexes

The antigen may be The antigen may be

1.1. EndogenousEndogenous as in SLE or as in SLE or

2.2. ExogenousExogenous as acute glomerulonephritis as acute glomerulonephritis follow certain follow certain

bacteria (Streptococci)bacteria (Streptococci) or or viral (HBV).viral (HBV).


Antigen antibody complexesAntigen antibody complexes are are formed in the circulation formed in the circulation and then and then trapped in the glomerulitrapped in the glomeruli, , where they where they produce injuryproduce injury through through binding of complement .binding of complement .


These IC are seen either byThese IC are seen either by Electron microscopyElectron microscopy as as

dense depositsdense deposits Immunofluorescence microscopyImmunofluorescence microscopy, as , as

granular depositsgranular deposits

granular immune depositsgranular immune deposits

Post-streptococcal glomerulonephritis is Post-streptococcal glomerulonephritis is immunologically mediated, immunologically mediated,

The immune deposits are distributed in the The immune deposits are distributed in the capillary loops in capillary loops in

A granular, bumpy pattern because of the A granular, bumpy pattern because of the focal nature of the deposition processfocal nature of the deposition process

((granular immune depositsgranular immune deposits))

B- nephritis in situB- nephritis in situ

The best example is The best example is anti glomerular anti glomerular basement membrane diseasebasement membrane disease..

In this type antibody are directed against In this type antibody are directed against fixed antigen in the GBM.fixed antigen in the GBM.

Also can react to planted non-glomerular Also can react to planted non-glomerular antigens interacting with intrinsic antigens interacting with intrinsic component component (Heymann’s model)(Heymann’s model)

B- nephritis in situB- nephritis in situ

Some times the anti GBM antibodies cross Some times the anti GBM antibodies cross react with basement membrane of alveoli react with basement membrane of alveoli resulting in simultaneous lung and kidney resulting in simultaneous lung and kidney disease disease (Good(Good Pasture syndrome).Pasture syndrome).

The antibody can be visualized along GBM The antibody can be visualized along GBM by indirect immunofluorescence microscopy, by indirect immunofluorescence microscopy, giving a characteristic giving a characteristic linear patternlinear pattern..

Antibody to IgG, has a smooth, diffuse, Antibody to IgG, has a smooth, diffuse, linear pattern that is characteristic for linear pattern that is characteristic for glomerular basement membrane antibody glomerular basement membrane antibody with Goodpasture's syndrome. with Goodpasture's syndrome.

Clinical findings of good pasture Clinical findings of good pasture syndromesyndrome

There is picture of RPGN with haematuria There is picture of RPGN with haematuria and may end in renal failure.and may end in renal failure.

Haemorraghic interstitial pneumonitis with Haemorraghic interstitial pneumonitis with haemoptysis, dyspnea,..haemoptysis, dyspnea,..

Iron ↓ anemia from recurrent hemorrahge.Iron ↓ anemia from recurrent hemorrahge.

Good Pasture SyndromeGood Pasture Syndrome

It is an example of It is an example of type II hypersensitivitytype II hypersensitivity with cytotoxic antibodieswith cytotoxic antibodies

Circulating anti GBM antibodies can be Circulating anti GBM antibodies can be detected in serum (by EIA).detected in serum (by EIA).

Renal biopsy:Renal biopsy: shows a characteristic shows a characteristic

linear immunofluorescence depositslinear immunofluorescence deposits of of IgGIgG and and C3.C3.

Good Pasture SyndromeGood Pasture Syndrome

Renal biopsy:Renal biopsy: shows a characteristic shows a characteristic

linear immunofluorescence depositslinear immunofluorescence deposits

of of IgGIgG and and C3.C3.

2- Cell mediated immunity2- Cell mediated immunity

2- Cell mediated immunity2- Cell mediated immunity

There is increasing evidence that sensitized There is increasing evidence that sensitized T cellsT cells can cause glomerular injury . can cause glomerular injury .

These may be the case in some forms of These may be the case in some forms of rapidly progressive glomerulonephritis.rapidly progressive glomerulonephritis.

Mediators of immune injuryMediators of immune injury

Glomerular damage is reflected Glomerular damage is reflected physiologically by physiologically by loss of barrier functionloss of barrier function manifested by manifested by proteinuriaproteinuria and and reduction of glomerular filtration ratereduction of glomerular filtration rate

(GFR). (GFR).

Mediators of immune injuryMediators of immune injury Many mechanisms are described:Many mechanisms are described:

Complement-leukocyte mechanismComplement-leukocyte mechanismC5-9 complement componentsC5-9 complement componentsCytotoxic antibodiesCytotoxic antibodiesMonocytes and macrophageMonocytes and macrophage..PlateletsPlatelets


1- Complement-leukocyte mechanism1- Complement-leukocyte mechanism: : Activation of complementActivation of complement Generation of chemotactic factorsGeneration of chemotactic factors (C5a) (C5a) Attract neutrophilsAttract neutrophils

1.1. Produce Produce ProteasesProteases which which degrade GBMdegrade GBM, ,

2.2. O2 freeO2 free radicalsradicals which which cause tissue damagecause tissue damage

3.3. Arachidonic acid metabolites (as TXA2) and Arachidonic acid metabolites (as TXA2) and which lead to which lead to reduction of GFR.reduction of GFR.


Endothelin & other vasoconstrictorsEndothelin & other vasoconstrictors also also contribute to reduction of GFR. contribute to reduction of GFR.

In addition GFR is also In addition GFR is also ↓↓ as a result of as a result of obstruction of glomerular lumenobstruction of glomerular lumen by by

1.1. infiltrating inflammatory cells and infiltrating inflammatory cells and

2.2. proliferating mesangial cells.proliferating mesangial cells.


2- C5-9 complement component2- C5-9 complement component: : This component causes This component causes epithelial damageepithelial damage. . It also It also up regulates the transforming growth up regulates the transforming growth

factor receptors on epithelial cellsfactor receptors on epithelial cells, and , and lead to lead to excessive synthesis of extra cellular excessive synthesis of extra cellular

matrix and GBM thickeningmatrix and GBM thickening..


3- Cytotoxic antibodies3- Cytotoxic antibodies: : antibodies directed against glomerular antibodies directed against glomerular

structure and produce cytotoxicity structure and produce cytotoxicity

(even if IC is absent)(even if IC is absent)


4- Monocytes and macrophage4- Monocytes and macrophage: : They secrete a number of biologically active They secrete a number of biologically active

mediators which contribute to glomerular mediators which contribute to glomerular damage.damage.

5- Platelet5- Platelet: : It aggregates in the glomerulus and release It aggregates in the glomerulus and release

PG and growth factors.PG and growth factors.


Epithelial injuryEpithelial injury: : is the most important factor in glomerular is the most important factor in glomerular

damage. damage. This can be induced byThis can be induced by

1.1. Antibody to visceral epitheliumAntibody to visceral epithelium or by or by

2.2. Toxins or othersToxins or others. .

Such injury is reflected Such injury is reflected 1.1. Morphologically by Morphologically by loss of foot processesloss of foot processes

2.2. Functionally by Functionally by proteinuria.proteinuria.

Nephrotic syndromeNephrotic syndrome

Nephrotic syndromeNephrotic syndrome Nephrotic syndrome refers to Nephrotic syndrome refers to clinical clinical

condition that include five main features;condition that include five main features;1.1. Massive proteinuria Massive proteinuria (more than 3.5 gm/day)(more than 3.5 gm/day)

2.2. Hypo-albuminaemia Hypo-albuminaemia (less than 3 gm/dl)(less than 3 gm/dl)

3.3. Generalized edemaGeneralized edema

4.4. Hyper-lipidaemia Hyper-lipidaemia (increase cholesterol & triglycerides)(increase cholesterol & triglycerides)

5.5. Lipiduria Lipiduria (Lipid casts in urine ).(Lipid casts in urine ).

At the onset renal function is normal (BUN, At the onset renal function is normal (BUN, creatinine) but later on it is impaired.creatinine) but later on it is impaired.

Pathogenesis of Nephrotic syndromePathogenesis of Nephrotic syndrome

The initial event is The initial event is damage to capillary walldamage to capillary wall resulting in resulting in increase permeability to plasma increase permeability to plasma

protein. protein. With long standing heavy proteinuria serum With long standing heavy proteinuria serum

albumin tend to become depleted and albumin tend to become depleted and decreased. decreased.

The The drop of osmotic pressuredrop of osmotic pressure will lead to will lead to generalized edemageneralized edema . .

Pathogenesis of Nephrotic syndromePathogenesis of Nephrotic syndrome

As fluid escape from vessels to tissues, As fluid escape from vessels to tissues,

1.1. there is there is decrease of plasma volumedecrease of plasma volume with with

2.2. compensatory secretion of compensatory secretion of aldosterone aldosterone

3.3. resulting in resulting in salt and water retentionsalt and water retention and and

4.4. further further aggravate the edema.aggravate the edema. Hypo-albuminaemia trigger Hypo-albuminaemia trigger increased increased

synthesis of lipids in the liver.synthesis of lipids in the liver.

Causes of Nephrotic syndromeCauses of Nephrotic syndrome

Nephrotic syndrome may be Nephrotic syndrome may be

1.1.PrimaryPrimary or or

2.2.Secondary.Secondary.

Causes of Nephrotic syndromeCauses of Nephrotic syndrome

Secondary nephrotic syndrome:Secondary nephrotic syndrome: Many disease can lead to Nephrotic Many disease can lead to Nephrotic

changes in the kidney as changes in the kidney as 1.1. DM, DM, 2.2. SLE, SLE, 3.3. Amyloidosis, Amyloidosis, 4.4. Drugs (gold, penicillamine), Drugs (gold, penicillamine), 5.5. Infection Infection

(malaria, syphilis, HBV, (malaria, syphilis, HBV, HIV, ..)HIV, ..)

Causes of nephrotic syndromeCauses of nephrotic syndrome Primary nephrotic syndrome:Primary nephrotic syndrome:

It is encountered in primary glomerular It is encountered in primary glomerular diseases as :diseases as :

1.1. Lipoid nephrosis Lipoid nephrosis (minimal change disease)(minimal change disease)

2.2. Membranous glomerulonephritisMembranous glomerulonephritis

3.3. Focal segmental glomerulosclerosisFocal segmental glomerulosclerosis

4.4. Membranoproliferative glomerulonephritisMembranoproliferative glomerulonephritis

Minimal change disease Minimal change disease lipoid nephrosislipoid nephrosis

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Minimal change diseaseMinimal change disease

This disease is also called This disease is also called lipoid nephrosislipoid nephrosis. . It is the most frequent cause of nephrotic It is the most frequent cause of nephrotic syndrome in children. syndrome in children.

It is characterized by normal appearance of It is characterized by normal appearance of glomeruli under light microscope, glomeruli under light microscope,

but it show but it show loss of visceral footloss of visceral foot processesprocesses when viewed under electron microscope.when viewed under electron microscope.

Lipoid nephrosisLipoid nephrosis

Pathogenesis:Pathogenesis:

The current evidence suggest that minimal The current evidence suggest that minimal change disease results from disorder in T change disease results from disorder in T cells. cells.

It is postulated that T cells elaborate a factor It is postulated that T cells elaborate a factor that affect nephrin synthesis.that affect nephrin synthesis.

Morphology of minimal change diseaseMorphology of minimal change disease

Light microscopyLight microscopy With With light microscopylight microscopy the glomeruli appear the glomeruli appear

nearly normal. nearly normal. The cells of proximal convoluted tubules The cells of proximal convoluted tubules

are are heavily laden with lipidsheavily laden with lipids and this is the and this is the basis of the name lipoid nephrosis. basis of the name lipoid nephrosis.

Slide 21.30

The cells of The cells of proximal convoluted tubulesproximal convoluted tubules are are

heavily laden with lipidsheavily laden with lipids (lipoid nephrosis).(lipoid nephrosis).

The cells of proximal convoluted tubules are The cells of proximal convoluted tubules are

heavily laden with lipidsheavily laden with lipids (lipoid nephrosis). (lipoid nephrosis).

Diffuse loss of the foot processes ofDiffuse loss of the foot processes of podocytespodocytes

Morphology of minimal change diseaseMorphology of minimal change disease

Electron microscopyElectron microscopy With With electron microscopy,electron microscopy, The only obvious abnormality is the The only obvious abnormality is the

uniform & diffuse uniform & diffuse loss of the foot loss of the foot processes ofprocesses of podocytespodocytes

This is minimal change disease (MCD) This is minimal change disease (MCD) loss of the epithelial cell (podocyte) foot loss of the epithelial cell (podocyte) foot

processes .processes .

Clinical courseClinical course

Gradual onset of nephrotic syndrome .Gradual onset of nephrotic syndrome . It affect only childrenIt affect only children.. Renal function is Renal function is preserved in most casespreserved in most cases.. Hypertension Hypertension is absentis absent.. Protein lossProtein loss is usually confined to small is usually confined to small

molecular proteins molecular proteins (selective proteinuria).(selective proteinuria).

Prognosis:Prognosis:

More than More than 90%90% of cases respond to of cases respond to corticosteroids.corticosteroids.

Recurrence may occur and CRF may Recurrence may occur and CRF may develop in less than develop in less than 5%5% of cases after of cases after about 25 years about 25 years

Membranous glomerulonephritis Membranous glomerulonephritis (MGN)(MGN)

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Membranous glomerulonephritis Membranous glomerulonephritis (MGN)(MGN)

It is a slowly progressive disease It is a slowly progressive disease AffectAffect adults adults between 30-50 years. between 30-50 years. It is characterized by the presence of It is characterized by the presence of

subepithelial immunoglobulin containing subepithelial immunoglobulin containing depositsdeposits along the GBM. along the GBM.

Diffuse thickening of GBMDiffuse thickening of GBM is shown under is shown under light microscopy in well developed cases. light microscopy in well developed cases.

Causes of MGNCauses of MGN

Primary Primary As a primary kidney involvement in As a primary kidney involvement in 85 85

% of cases (idiopathic) .% of cases (idiopathic) . It results from antibodies that It results from antibodies that react react in situin situ

to endogenous glomerular antigen. to endogenous glomerular antigen. The glomerular damage is due to the action The glomerular damage is due to the action

of of C5-9 lytic components of complement.C5-9 lytic components of complement.

Causes of MGNCauses of MGN

Secondary:Secondary:MGN may occur MGN may occur secondary to secondary to Many known disorders asMany known disorders as

1.1. HBV,HBV,2.2. Syphilis Syphilis 3.3. Malaria Malaria 4.4. SLESLE

Exposure to inorganic salts as Exposure to inorganic salts as 1.1. Gold Gold 2.2. MercuryMercury

Exposure to drugs asExposure to drugs as 1.1. Penicillamin captopril Penicillamin captopril 2.2. Non-steroidal anti-inflammatory drugs.Non-steroidal anti-inflammatory drugs.

Morphology of MGNMorphology of MGN

The basic change seen by light microscope The basic change seen by light microscope is is diffuse thickening of GBM. diffuse thickening of GBM.

By electron microscopyBy electron microscopy ,there is ,there is subepithelial deposits along GBM as wellsubepithelial deposits along GBM as well as as loss of foot processes. loss of foot processes.

Diffuse thickening of GBM.Diffuse thickening of GBM.

Subepithelial deposits along GBM as wellSubepithelial deposits along GBM as well as loss of foot processes.as loss of foot processes.

Morphology of MGNMorphology of MGN

With further progression glomeruli become With further progression glomeruli become sclerosed and hyalinizedsclerosed and hyalinized. .

Immunoflurescence stainingImmunoflurescence staining of patient of patient glomerulus show glomerulus show typical granular depositiontypical granular deposition of of immunoglobulin immunoglobulin and and complementcomplement along along GBM.GBM.

Membranous glomerulonephritis in which the capillary loops are Membranous glomerulonephritis in which the capillary loops are

thickened & prominent, but the cellularity is not increased.thickened & prominent, but the cellularity is not increased.

silver stain of the glomerulus highlights the proteinaceous basement membranes in silver stain of the glomerulus highlights the proteinaceous basement membranes in black. There are characteristic "spikes" seen with membranous glomerulonephritis black. There are characteristic "spikes" seen with membranous glomerulonephritis in which the black basement membrane material appears as projections around in which the black basement membrane material appears as projections around the capillary loops. the capillary loops.

By electron microscopy in membranous glomerulonephritis,By electron microscopy in membranous glomerulonephritis, the darker electron dense immune subepithelial deposits the darker electron dense immune subepithelial deposits are seen scattered within the thickened basement membrane.are seen scattered within the thickened basement membrane.

Membranous glomerulonephritis appear Membranous glomerulonephritis appear in a in a diffuse granular patterndiffuse granular pattern by immunofluorescence. by immunofluorescence.

Clinical picture of MGNClinical picture of MGN

Gradual onset of nephrotic syndrome.Gradual onset of nephrotic syndrome. It affect It affect only adultsonly adults,, In contrast to lipoid nephrosis, In contrast to lipoid nephrosis,

proteinuria is proteinuria is not selectivenot selective (i.e. ↑permeability also to large size proteins as globulins)(i.e. ↑permeability also to large size proteins as globulins)

Does not respondDoes not respond to corticosteroids to corticosteroids..

Clinical picture of MGNClinical picture of MGN

40%40% of patients suffer from of patients suffer from progressive diseaseprogressive disease terminating in terminating in renal failure after renal failure after 2 - 20 years2 - 20 years..

It is necessary to rule out secondary It is necessary to rule out secondary causes.causes.

Compare lipoid nephrosis A & C with membranous GN B & D

(FSG)(FSG)

Focal segmental Focal segmental glomerulosclerosis glomerulosclerosis

(FSG)(FSG)

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Focal segmental glomerulosclerosis Focal segmental glomerulosclerosis (FSG)(FSG)

FSG is characterized FSG is characterized histologically by sclerosis affecting histologically by sclerosis affecting

1.1. Some but notSome but not all glomeruli all glomeruli (focal)(focal)

2.2. Involving Involving only segments of only segments of each glomeruluseach glomerulus (segmental).(segmental).

Causes of FSGCauses of FSG

Primary or idiopathic:Primary or idiopathic: FSG account for about FSG account for about 10%10% of all cases of of all cases of

nephrotic syndrome. nephrotic syndrome. It affect It affect both children and adult. both children and adult. In children it is important to be differentiated In children it is important to be differentiated

from minimal change disease. from minimal change disease.


The following aspects are found in The following aspects are found in FSG onlyFSG only not found in minimal change disease;not found in minimal change disease;

Hypertension, Hypertension, Non-selective proteinuria, Non-selective proteinuria, Haematuria, Haematuria, Poor response to corticosteroid. Poor response to corticosteroid. Poor prognosis ,Poor prognosis ,

50% develop CRF50% develop CRF within 10 years within 10 years


Secondary FSG:Secondary FSG: occur in occur in HIV nephropathy, HIV nephropathy, IgA nephropathy ,….IgA nephropathy ,….

Morphology of FSGMorphology of FSG

The disease affect only some of glomeruli The disease affect only some of glomeruli (focal)(focal) initially the juxtamedullary glomeruli. initially the juxtamedullary glomeruli.

It affect only some tufts within the It affect only some tufts within the glomerulus and sparing the others glomerulus and sparing the others (segmental).(segmental).

The lesion exhibit The lesion exhibit 1.1. Increased mesangial matrixIncreased mesangial matrix and and

2.2. Deposition of hyaline masses and lipid droplets. Deposition of hyaline masses and lipid droplets.

FSG morphologyFSG morphology

On electron microscopyOn electron microscopy , ,1.1. Visceral epithelium show loss of foot processes as in Visceral epithelium show loss of foot processes as in

lipoid nephrosis and also lipoid nephrosis and also

2.2. Greater degree of epithelial detachmentGreater degree of epithelial detachment

On progression On progression 1.1. Glomeruli are completely sclerosed Glomeruli are completely sclerosed (global sclerosis)(global sclerosis)

2.2. With tubular atrophy.With tubular atrophy.

This is focal segmental glomerulosclerosis (FSGS). This is focal segmental glomerulosclerosis (FSGS). An area of collagenous sclerosis runs across the middle of this glomerulus.An area of collagenous sclerosis runs across the middle of this glomerulus.

Membranoproliferative Membranoproliferative glomerulonephritis glomerulonephritis

(MPGN)(MPGN)

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Membranoproliferative glomerulonephritis (MPGN)Membranoproliferative glomerulonephritis (MPGN)

MPGN is manifested histologically by MPGN is manifested histologically by 1.1. Alterations of basement membrane & mesangium Alterations of basement membrane & mesangium

2.2. Proliferation of glomerular cells. Proliferation of glomerular cells.

It affect both children andIt affect both children and adultadult. . It account for It account for 10-15 %10-15 % of cases of of cases of

nephrotic syndromenephrotic syndrome

Pathogenesis of MPGNPathogenesis of MPGN

Two types are recognized. Two types are recognized. Most cases of Most cases of type I MPGNtype I MPGN appear to be caused appear to be caused

by circulating IC. by circulating IC. It could be also secondary to SLE, HBV, and other It could be also secondary to SLE, HBV, and other

conditions .conditions . The pathogenesis of The pathogenesis of type II MPGNtype II MPGN is not clear . is not clear . It could result from activation of alternative It could result from activation of alternative

complement pathway through C3 nephritic factor.complement pathway through C3 nephritic factor.

Morphology of MPGNMorphology of MPGN

By light microscopeBy light microscope both types of MPGN are both types of MPGN are similar. similar.

The glomeruli are The glomeruli are 1.1. large large

2.2. Proliferation of mesangiumProliferation of mesangium, ,

3.3. Infiltrating leucocytesInfiltrating leucocytes

4.4. lobular appearancelobular appearance. .


The GBM is thickened and show The GBM is thickened and show double double contourcontour appearance.appearance.

This splitting of GBMThis splitting of GBM is caused by is caused by mesangial cells inclusion between GBM mesangial cells inclusion between GBM laminae. laminae.

It is not easily seen by ordinary microscope. It is not easily seen by ordinary microscope. EM or special stain is required. EM or special stain is required.

Membranoproliferative glomerulonephritis (MPGN).Membranoproliferative glomerulonephritis (MPGN).

Glomerulus has increased overall cellularity, mainly mesangialGlomerulus has increased overall cellularity, mainly mesangial


Immunofluorescence and electron Immunofluorescence and electron microscopy differentiate between the two microscopy differentiate between the two types of MPGN; types of MPGN;

type I MPGN is characterized by type I MPGN is characterized by subendothelialsubendothelial depositsdeposits(C3 and IgG).(C3 and IgG).

Type II MPGN is characterized by Type II MPGN is characterized by intramembranous denseintramembranous dense deposits deposits of C3 of C3 mainly (dense deposit disease)mainly (dense deposit disease)

Interposed mesangial

cell process

Subendothelial deposit

Intramembranous deposit

TYPE I

TYPE II

A mesangial cell at the lower left that is interposing its cytoplasm at the arrow into the A mesangial cell at the lower left that is interposing its cytoplasm at the arrow into the basement membrane, leading to splitting and reduplication of basement membrane. basement membrane, leading to splitting and reduplication of basement membrane.

This is MPGN type I. These are characteristic subendothelial immune deposits. This is MPGN type I. These are characteristic subendothelial immune deposits.

This EM demonstrates the dense deposits in the basement membrane of MPGN type II. This EM demonstrates the dense deposits in the basement membrane of MPGN type II. There are dark electron dense deposits within the basement membrane There are dark electron dense deposits within the basement membrane that often coalesce to form a ribbon-like mass of depositsthat often coalesce to form a ribbon-like mass of deposits

Clinical picture of MPGNClinical picture of MPGN

Nephrotic syndromeNephrotic syndrome is present in is present in 50% of 50% of

casescases.. 40% progress40% progress to CRF. to CRF. Type IIType II has a has a worse prognosisworse prognosis..

Clinical picture of MPGNClinical picture of MPGN

However MPGN may begin with However MPGN may begin with Acute Acute nephritic syndromenephritic syndrome With With haematuria & mild proteinuriahaematuria & mild proteinuria

Others has a combined Others has a combined nephritic- nephroticnephritic- nephrotic picture. picture.

Nephritic SyndromeNephritic Syndrome

Nephritic SyndromeNephritic Syndrome It is a clinical complex usually of acute onsetIt is a clinical complex usually of acute onset

characterized by characterized by five criteriafive criteria::1.1. HaematuriaHaematuria with diagnostic with diagnostic red cell castsred cell casts..

2.2. OliguriaOliguria and and impairment of kidney functionimpairment of kidney function..

3.3. Hypertension.Hypertension.

4.4. Mild proteinuriaMild proteinuria..

5.5. Mild edemaMild edema (localized to face) (localized to face)

PathogenesisPathogenesis GFR is decreasedGFR is decreased due to obstruction of due to obstruction of

glomerular lumen by glomerular lumen by The proliferating glomerular cellsThe proliferating glomerular cells Infiltrating inflammatory cellsInfiltrating inflammatory cells Due to haemodynamic changes Due to haemodynamic changes

(vasoconstriction). (vasoconstriction).

The The inflammatory reactions injure the inflammatory reactions injure the capillary wallcapillary wall and and produce hematuriaproduce hematuria..

pathogenesispathogenesis

Reduced GFRReduced GFR is manifested clinically by is manifested clinically by oliguriaoliguria. . HypertensionHypertension is the result of both is the result of both

1.1. Fluid retention and Fluid retention and

2.2. Renin release from ischemic kidney.Renin release from ischemic kidney. Acute nephritic syndrome may be produced Acute nephritic syndrome may be produced

SecondarySecondary to other disorders as SLE or to other disorders as SLE or may as a result of may as a result of PrimaryPrimary glomerular disease glomerular disease..

Kidney Diseases Associated WithKidney Diseases Associated With Nephritic SyndromeNephritic Syndrome

1.1. Acute diffuse proliferative post streptococcal Acute diffuse proliferative post streptococcal glomerulonephritis glomerulonephritis The commonest typeThe commonest type

2.2. Rapidly progressive glomerulonephritis Rapidly progressive glomerulonephritis (Crescentic) (Crescentic)

3.3. IgA nephropathy IgA nephropathy (Berger Disease)(Berger Disease)

4.4. Hereditary nephritisHereditary nephritis

5.5. Chronic glomerulonephritisChronic glomerulonephritis

Acute diffuse proliferative post Acute diffuse proliferative post streptococcal glomerulonephritis streptococcal glomerulonephritis

(PGN)(PGN)

Acute diffuse proliferative post Acute diffuse proliferative post streptococcal glomerulonephritis streptococcal glomerulonephritis

(PGN)(PGN)

1

Acute diffuse proliferative post streptococcal glomerulonephritis (PGN)Acute diffuse proliferative post streptococcal glomerulonephritis (PGN)

It is one of the more common glomerular disease It is one of the more common glomerular disease typically caused by Immune complex. typically caused by Immune complex.

The commonest organism is The commonest organism is streptococci,streptococci, however it can be caused by however it can be caused by

1.1. Pneumococci. Pneumococci. 2.2. Staphylococci, Staphylococci, 3.3. Viruses asViruses as

MeaslesMeasles MumpsMumps..

Acute diffuse proliferative post streptococcal glomerulonephritis (PGN)Acute diffuse proliferative post streptococcal glomerulonephritis (PGN)

PGN is an IC disease . PGN is an IC disease . IC are deposited as IC are deposited as granular patterngranular pattern on GBM on GBM there is also blood there is also blood decrease of complementdecrease of complement

(due to increase consumption).(due to increase consumption).

Morphology of PGNMorphology of PGN

Light microscopyLight microscopy

Increased cellularity of glomerular tuftIncreased cellularity of glomerular tuft Affect all glomeruli and hence it is termed diffuse.Affect all glomeruli and hence it is termed diffuse.

This is caused mainly by three cells:This is caused mainly by three cells:1.1. Proliferation and swelling of Proliferation and swelling of endothelial cellsendothelial cells

2.2. Proliferation of Proliferation of mesangial cellsmesangial cells

3.3. Infiltration by Infiltration by neutrophils and macrophagesneutrophils and macrophages


In few cases there may be also crescent In few cases there may be also crescent inside bowman capsule.inside bowman capsule.

Electron Microscopy:Electron Microscopy: Show immune complex deposits Show immune complex deposits Arranged Arranged subepithelialsubepithelial along GBM along GBM

(called (called humpshumps))


Immuno fluorescence microscopyImmuno fluorescence microscopy

Characteristic Characteristic granular depositsgranular deposits of of IgG & complementIgG & complement..

This glomerulus isThis glomerulus is hypercellularhypercellular and capillary loops are poorly defined. and capillary loops are poorly defined.

The hypercellularity of post-streptococcal glomerulonephritis is due to increased The hypercellularity of post-streptococcal glomerulonephritis is due to increased numbers of numbers of epithelial, endothelial, and mesangial cellsepithelial, endothelial, and mesangial cells as well as as well as neutrophilsneutrophils in and in and around the capillary loops.. around the capillary loops.. (high power)(high power)

By electron microscopy, the electron dense immune deposits of post-By electron microscopy, the electron dense immune deposits of post-streptococcal glomerulonephritis are predominantly subepithelial, as seen streptococcal glomerulonephritis are predominantly subepithelial, as seen here with a large subepithelial "hump" at the right of the basement here with a large subepithelial "hump" at the right of the basement membrane (BM). membrane (BM).

Clinical picture of PGNClinical picture of PGN

History of previous streptococcal infection History of previous streptococcal infection 2-3 weeks before2-3 weeks before..

Onset is Onset is sudden with fever ,and malaisesudden with fever ,and malaise.. There is picture of nephritic syndrome There is picture of nephritic syndrome

1.1. Oliguria ,Oliguria ,

2.2. Haematuria, Haematuria,

3.3. HypertensionHypertension

Laboratory finding of PGNLaboratory finding of PGN

1- 1- urine urine : : Smoky in color, Smoky in color, Many Many RBCsRBCs are found, are found, DiagnosticDiagnostic red cell castsred cell casts

Laboratory finding of PGNLaboratory finding of PGN

2- Evidence of recent streptococcal 2- Evidence of recent streptococcal infection: infection:

1.1. Increased ASOT Increased ASOT

2.2. Anti DNAseAnti DNAse

3- Mild elevation of 3- Mild elevation of urea and creatinineurea and creatinine.. 4- 4- Decreased serum complementDecreased serum complement..

Prognosis of PGNPrognosis of PGN

RecoveryRecovery occur in occur in most childrenmost children..

Few cases develop RPGN.Few cases develop RPGN.(Rapidly progressive glomerulonephritis)(Rapidly progressive glomerulonephritis)

In adult In adult 15-50%15-50% develop develop ESRDESRD (End stage renal disease) (End stage renal disease) over few years over few years

Rapidly progressive Rapidly progressive glomerulonephritis glomerulonephritis

(RPGN) (RPGN) (Crescentic), (Crescentic),

Rapidly progressive Rapidly progressive glomerulonephritis glomerulonephritis

(RPGN) (RPGN) (Crescentic), (Crescentic),

22

2-Rapidly progressive ,(Crescentic), glomerulonephritis (RPGN)2-Rapidly progressive ,(Crescentic), glomerulonephritis (RPGN)

RPGN is characterized by RPGN is characterized by 1.1. Rapid and progressive loss of renal function Rapid and progressive loss of renal function 2.2. Associated with severe oliguria and Associated with severe oliguria and 3.3. Death from renal failure within weeks if not treated.Death from renal failure within weeks if not treated.

RPGN may be caused by many diseases,RPGN may be caused by many diseases,1.1. Some are Some are Restricted to the kidneyRestricted to the kidney2.2. OthersOthers areare systemic systemic. .

Types of RPGNTypes of RPGN

Three typesThree types are recognized: are recognized:Type IType I

It is due to It is due to anti GBM antibodyanti GBM antibody. The typical . The typical example is example is good pasture syndromegood pasture syndrome. .

Diagnosis of this type is important because Diagnosis of this type is important because the patient improve from treatment by the patient improve from treatment by plasmapheresisplasmapheresis which remove pathological which remove pathological antibodiesantibodies

Types OF RPGNTypes OF RPGN

Type IIType II It is an immune complex mediated disorder. It is an immune complex mediated disorder. It can be a complication of any IC nephritis as It can be a complication of any IC nephritis as

post streptococcal GN, post streptococcal GN, IgA nephropathy, IgA nephropathy, henoch-schonlien purpura, and SLE. henoch-schonlien purpura, and SLE. In some cases the underlying cause is unknown. In some cases the underlying cause is unknown.

Immunofluorescence studies reveal Immunofluorescence studies reveal granulargranular deposition of ICdeposition of IC

Types of RPGNTypes of RPGNType III:Type III:

It is also called It is also called pauci-immune typepauci-immune type . . There is There is no anti GBM or ICno anti GBM or IC by by

immunofluorescence or even by EMimmunofluorescence or even by EM.. Most of these patients have Most of these patients have

Anti Neutrophil Cytoplasmic Antibodies Anti Neutrophil Cytoplasmic Antibodies in in serum. serum. (ANCA)(ANCA)

These antibodies play a role in some vasculitisThese antibodies play a role in some vasculitis. .

Types of RPGNTypes of RPGNType III:Type III:

This type may be associated with This type may be associated with disorders of systemic vasculitis as disorders of systemic vasculitis as

1.1. PAN PAN

2.2. wegener granulomatosiswegener granulomatosis. . However in many cases this type is However in many cases this type is

1.1. Limited to the kidneyLimited to the kidney & &

2.2. Idiopathic.Idiopathic.

Morphology of RPGNMorphology of RPGN

Histological pictureHistological picture is characterized by the is characterized by the presence of presence of crescents increscents in most of the most of the glomeruliglomeruli. (Crescentic GN).. (Crescentic GN).

Crescents are formed by Crescents are formed by 1.1. Proliferation of parietal cells Proliferation of parietal cells of the bowman capsule of the bowman capsule

2.2. Infiltration of Infiltration of mononuclear cellsmononuclear cells and and

3.3. Deposition of Deposition of fibrinfibrin within bowman space. within bowman space.

Morphology of RPGNMorphology of RPGN

The crescents eventually obliterate The crescents eventually obliterate bowman space and compress the glomeruli. bowman space and compress the glomeruli.

EM EM may reveal subepithelial deposits in may reveal subepithelial deposits in some casessome cases

Note in the lower left glomerulus that Note in the lower left glomerulus that the capillary loops are markedly thickenedthe capillary loops are markedly thickened(the so-called "wire loop" lesion of lupus nephritis(the so-called "wire loop" lesion of lupus nephritis..

Seen here within the glomeruli are Seen here within the glomeruli are crescentscrescents composed of proliferating epithelial cells. composed of proliferating epithelial cells.

Another glomerulus with epithelial crescentsAnother glomerulus with epithelial crescents squashing the glomerular tufts from all sides.squashing the glomerular tufts from all sides.

RPGN may be RPGN may be idiopathic or idiopathic or may result from may result from

1.1. SLE, SLE,

2.2. Post-infectious GN Post-infectious GN (some cases of post-streptococcal GN), (some cases of post-streptococcal GN),

3.3. Various types of vasculitis, and Various types of vasculitis, and

4.4. Goodpasture's syndromeGoodpasture's syndrome. .

With a rapidly progressive GN, the glomerular damage is so severe that fibrinogen With a rapidly progressive GN, the glomerular damage is so severe that fibrinogen leaks into Bowman's space, leading to proliferation of the epithelial cells leaks into Bowman's space, leading to proliferation of the epithelial cells and formation of a crescentand formation of a crescent

This immunofluorescence micrograph of a glomerulus demonstratesThis immunofluorescence micrograph of a glomerulus demonstrates positivity with antibody to fibrinogen.positivity with antibody to fibrinogen.

Clinical picture of RPGNClinical picture of RPGN

Onset is rapid with Onset is rapid with marked oliguriamarked oliguria and and azotemia azotemia (Increase urea and creatinine).(Increase urea and creatinine).

AnuriaAnuria may occur in some cases (require may occur in some cases (require dialysis).dialysis).

Prognosis is not goodPrognosis is not good, renal failure occur , renal failure occur within weeks if proper treatment in not done within weeks if proper treatment in not done rapidly.rapidly.

IgA nephropathyIgA nephropathy (Berger disease) (Berger disease)

33

IgA nephropathy (Berger disease)IgA nephropathy (Berger disease)

It is one of the most common causes of It is one of the most common causes of recurrent gross or microscopic hematuria.recurrent gross or microscopic hematuria.

Pathogenesis:Pathogenesis: Increase IgA concentrationIncrease IgA concentration is found in more than is found in more than

50% of cases. 50% of cases. Patients with IgA nephropathy have Patients with IgA nephropathy have increased increased

production of IgA in bone marrow. production of IgA in bone marrow. Also there is Also there is abnormalities in IgA clearanceabnormalities in IgA clearance. .

Pathogenesis of IgA nephropathyPathogenesis of IgA nephropathy

It may be It may be geneticgenetic and associated with HLA and associated with HLA typestypes

It could also be It could also be acquiredacquired due to increase IgA due to increase IgA synthesis in response to respiratory or GIT synthesis in response to respiratory or GIT infection. infection.

Pathogenesis of IgA nephropathyPathogenesis of IgA nephropathy

IgA nephropathy occur also in increased IgA nephropathy occur also in increased frequency frequency in patients with celiac diseasein patients with celiac disease (intestinal mucosal defect).(intestinal mucosal defect).

IgA and IgA complexes are then IgA and IgA complexes are then entrapped entrapped in mesangiumin mesangium where they activate where they activate alternative complement pathway and initiate alternative complement pathway and initiate glomerular injury.glomerular injury.

Morphology of Berger diseaseMorphology of Berger disease

The lesions vary considerably.The lesions vary considerably. The glomeruli may show The glomeruli may show focal and segmentalfocal and segmental

mesangial proliferationmesangial proliferation or or diffuse proliferationdiffuse proliferation.. Immunofluorescence staining show a Immunofluorescence staining show a

characteristic mesangial deposition of IgA characteristic mesangial deposition of IgA often often with C3 andwith C3 and properdin.properdin.

EMEM demonstrate electron demonstrate electron dense deposits in the dense deposits in the mesangium.mesangium.

Slide 21.38

This is Berger's disease, or IgA nephropathy.This is Berger's disease, or IgA nephropathy.

The IgA is deposited mainly in mesangium, which thenThe IgA is deposited mainly in mesangium, which then increases mesangial cellularity as shown at the arrow.increases mesangial cellularity as shown at the arrow.

This immunofluorescence micrograph demonstrates positivity with antibody to IgA. This immunofluorescence micrograph demonstrates positivity with antibody to IgA. Note that the pattern is that of Note that the pattern is that of mesangial staining. mesangial staining. This is IgA nephropathyThis is IgA nephropathy. (Berger. (Berger Disease)Disease)

Clinical picture of Berger diseaseClinical picture of Berger disease

The disease often present with The disease often present with grossgross hematuriahematuria after infection of respiratory tract after infection of respiratory tract or GIT. or GIT.

It affects It affects children or young adultschildren or young adults 30-40%30-40% has only has only microscopic hematuriamicroscopic hematuria..

Clinical picture of Berger diseaseClinical picture of Berger disease

Diagnosis depend on renal biopsy with Diagnosis depend on renal biopsy with immunofluorescence mesangial IgA immunofluorescence mesangial IgA deposition.deposition.

It is usually recurrent.It is usually recurrent. Many patients maintain normal renal function, Many patients maintain normal renal function, CRF occur in CRF occur in 25% of cases25% of cases after many years. after many years.

Hereditary nephritisHereditary nephritis

44


The most important disease is The most important disease is Alport’s syndrome .Alport’s syndrome . It is hereditary nephritis associated with nerve It is hereditary nephritis associated with nerve

deafness and eye disorders (cataract,…).deafness and eye disorders (cataract,…). It is due to gene abnormalities which encode It is due to gene abnormalities which encode

collagen production and so interfere with GBM collagen production and so interfere with GBM structurestructure

It affect male more frequently between 5-20 years.It affect male more frequently between 5-20 years.


MorphologyMorphology

A characteristic A characteristic foam cellsfoam cells is present due to is present due to accumulation of fat. accumulation of fat.

There is glomerular proliferation.There is glomerular proliferation.


Clinical pictureClinical picture Patients present with Patients present with

1.1. Haematuria, Haematuria,

2.2. Proteinuria Proteinuria

3.3. Nerve deafness and Nerve deafness and

4.4. Eye problems.Eye problems.

CRF may develop within yearsCRF may develop within years

Alport's syndromeAlport's syndrome

The renal tubular cells appear foamy The renal tubular cells appear foamy because of the accumulation of neutral fats and mucopolysaccharides. because of the accumulation of neutral fats and mucopolysaccharides. The glomeruli show irregular thickening and splitting of basement membranesThe glomeruli show irregular thickening and splitting of basement membranes

Chronic glomerulonephritisChronic glomerulonephritis(CGN)(CGN)

Chronic glomerulonephritisChronic glomerulonephritis(CGN)(CGN)

55

Chronic glomerulonephritis (CGN)Chronic glomerulonephritis (CGN)

CGN is a most important cause of ESRD CGN is a most important cause of ESRD (end stage renal disease) presenting as (end stage renal disease) presenting as CRF. CRF.

It probably represents the end stage of It probably represents the end stage of many disease as RPGN, FSG,MGN and many disease as RPGN, FSG,MGN and MPGN. MPGN.

However 20% of cases arise with no However 20% of cases arise with no history of symptomatic renal diseasehistory of symptomatic renal disease

Slide 21.42

Morphology of CGNMorphology of CGN

Gross:Gross: the kidneys are the kidneys are symmetricallysymmetrically contracted with diffuse granular surface.contracted with diffuse granular surface.

Microscopically:Microscopically: There is wide spread There is wide spread replacement of glomerular tuft by avascular replacement of glomerular tuft by avascular acellular hyaline materials acellular hyaline materials (hyalinization)(hyalinization) with complete glomerular obliteration. with complete glomerular obliteration.

There is also marked interstitial fibrosis and There is also marked interstitial fibrosis and tubular atrophy (due to impact on its blood tubular atrophy (due to impact on its blood flow) flow)

Slide 21.43

•Chronic glomerulonephritisChronic glomerulonephritis•Complete replacement of glomeruli by Complete replacement of glomeruli by blue stained collagen (Masson trichrome)blue stained collagen (Masson trichrome)

Clinical picture of CGN Clinical picture of CGN

Gradual onset ,usually discovered late in its Gradual onset ,usually discovered late in its course after the onset of renal insufficiency.course after the onset of renal insufficiency.

First manifestations include First manifestations include hypertension ,proteinuria ,haematuria, hypertension ,proteinuria ,haematuria, azotemiaazotemia

Progression to CRF and death unless renal Progression to CRF and death unless renal dialysis or transplantation is done.dialysis or transplantation is done.

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Health & Medicine

Glomerulus and nephrotic & nephritic syndrome