Libyan International Medical University
Faculty Of AMS
2rd year (2020-2021)
Block : Renal system
Week I
Glomerular disease I
Dr: Warda Musbah
Dr. Warda Musbah
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Intended learning outcomes
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By the end of this session you will be able to:
 Describe the pathogenesis and mechanism of glomerular
damage
 Outline mediators of glomerular damage and recognized
the different mechanisms of progression in glomerular
disease.
 List classification of glomerular disease and list causes of
nephrotic syndrome.
PATHOGENESIS OF GLOMERULAR
INJURY
1. Antibody-Mediated Injury
 In situ immune complex deposition
 Circulating immune complex deposition
2. Cytotoxic Antibodies
3. Cell-Mediated Immune Injury
4. Activation of Alternative Complement Pathway
Antibody-Mediated Injury
1. In Situ immune complex disease
Anti-GBM antibody induced nephritis
Heymann nephritis
Antibodies against planted antigens
1. In Situ immune complex disease
Anti-GBM antibody induced nephritis
The antibodies are directed against intrinsic fixed antigens
that are normal components of (GBM) proper resulting
in a diffuse linear pattern of staining for the antibodies by
immunofluorescence techniques.
This is the model of anti-GBM disease (Goodpasture syndrome)
which is caused by antibodies against non-collagenous domain of
the alpha 3 chain of collagen type IV.
1. In Situ immune complex disease
Heymann nephritis
The antibodies are directed against intrinsic fixed antigen called
Heymann antigen or ‘megalin’ located on visceral epithelial cells
resulting in complement activation and the formation of
subepithelial deposits and a granular pattern of staining for the
antibodies by immunofluorescence techniques.
1. In Situ immune complex disease
Antibodies against planted antigens
Antibodies can react with antigens that are not normally present in
the glomerulus but are “planted” there.
These antigens include cationic molecules like DNA, nuclear
proteins, bacterial, viral and parasitic products and drugs.
A granular pattern of staining is observed by immunofluorescence
techniques.
2. Circulating immune complex disease
o The glomerular injury is caused by entrapment of circulating
antigen-antibody complex within the glomeruli.
o This results in complement activation, leukocytic infiltration and
proliferation of glomerular and mesangial cells.
o The endogenousantigens include DNA and tumor antigens
o the exogenous antigens include infectious products.
o Granular deposits along the basement membrane, in the
mesangium or both by IHC .
Mediators of Immune Injury
• The mediators—both cells and molecules—are the usual suspects
involved in acute and chronic inflammation
Cells:
• Neutrophils and monocytes
• Macrophages and T lymphocytes
• Platelets
• Resident glomerular cells
Soluble Mediators:
• Complement activation
• Eicosanoids, nitric oxide, angiotensin, and endothelin
• Cytokines particularly IL-1 and TNF
• Chemokines(PDGF), (TGF-β), (VEGF).
Mechanisms of Progression in Glomerular
Diseases
The two major histologic characteristics of such
progressive renal damage are:
Glomerulosclerosis
 Tubulointerstitial fibrosis.
Glomerulosclerosis
Sclerosis involving portions of some glomeruli (also referred to as
secondary FSGS develops after many types of renal injury and
can lead to proteinuria and increasing functional impairment.
Glomerular sclerosis may be seen even in cases in which the
primary disease was non glomerula.
Tubular Injury and Interstitial Fibrosis
Tubulointerstitial injury, manifested by tubular damage
and interstitial inflammation, is a component of many
acute and chronic glomerulonephritides.
Tubulointerstitial fibrosis contributes to progression in both
immune and nonimmune glomerular diseases, for example,
diabetic nephropathy.
Indeed, there is often a much better correlation of decline in
renal function with the extent of tubulointerstitial damage than
with the severity of glomerular injury.
Glomerular diseases
Glomerular diseases encompass a large and clinically significant
group of renal diseases.
classify glomerular diseases into 2 broad groups:
I. Primary glomerulonephritis in which the glomeruli are the
predominant site of involvement.
II. Secondary glomerular diseases include certain systemic
and hereditary diseases which secondarily affect the glomeruli.
Clinical Manifestations of Glomerular Diseases
Syndrome
Manifestations
Nephritic syndrome
Hematuria, azotemia, variable proteinuria,
oliguria, edema, and hypertension
Rapidly progressive
glomerulonephritis
Acute nephritis, proteinuria, and acute
renal failure
Nephrotic syndrome
>3.5 g/day proteinuria, hypoalbuminemia,
hyperlipidemia, lipiduria
Chronic kidney
disease
Azotemia → uremia progressing for
months to years
Isolated urinary
abnormalities
Glomerular hematuria and/or
subnephrotic proteinuria
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References
• Robbins pathologic basis of diseases , 10th
edition, 2020.
• Harsh Mohan, textbook of pathology, 7th
edition , 2015.
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