This is about glomerulonephritis and all that you need to know. It contains different images illustrating this subject matter, well defined outline, different aspect of glomerulonephritis, which include acute and chronic glomerulonephritis, nephritic and nephrotic syndrome, investigations, how to diagnose glomerulonephritis, treatment and important discussions on Glomerulonephritidis. It is a presentation you need to check out.

1. GLOMERULONEPHRITIDES
AKINMOLADUN PRECIOUS TITILOPE
CLI/2017/033

2. Outline
• Introduction
• Normal structure of the kidney
• Glomerulonephritis
• Epidemiology
• Risk factors
• Aetiology
• Pathogenesis
• Broad Classifications
• Hereditary and systemic disorders causing glomerular lesions.
• Investigations
• Conclusion

3. Introduction
• Glomerular diseases encompass a large and clinically significant
group of renal diseases
• The disease severity varies from asymptomatic microscopic haematuria
to rapidly progressing renal failure.
• Glomerulopathy is a word that encompasses any disease of the
glomeruli, whether inflammatory or not.
• Glomerulonephritis refers to inflammation of theglomeruli.
• How about glomerulonephritides?

4. Normal anatomy of the kidney
• Brief embryology.
• Each human kidney weighs about
150g.
• Functions: A WET BED
• Anatomy of the normal kidney.
• Blood vessels.
• Kidneys from the standpoint of
diseasewill be divided into:
glomeruli, tubules, interstitium,
Blood vessels(BV)

5. Normal Kidney Histology

6. Glomerulus
• The glomerulus consists of an anatosmosing network of capillaries with
fenestrated endothelium invested by two layers of epithelium.
• It performs the function of filtering the blood.
• The capillary wall is madeup of:
1. Endothelial cells
2. Glomerular basement membrane (GBM)
3. Visceralepithelial cells (podocytes)
• Note the function of mesangial matrix and cells

8. Definition
• Glomerulonephritis or
Bright’s
disease(archaic term)
is inflammation of
the tiny filters in the
kidneys (glomeruli).

9. Epidemiology
• GN represents 10-15% of glomerular diseases. Variable incidence has been
reported, in part because of the subclinical nature of the disease in more than
half the affected population.
• Glomerulonephritis constitutes 25% to 30% of all end-stage renal disease
cases
• Glomerulonephritis is a relatively common condition worldwide. The
prevalence varies significantly across different regions and populations. It
affects individuals of all ages, from children to elderly.
• Some form of glomerulonephritis is also predominant in people suffering
from various diseases like SLE, diabetes and other autoimmune disorders.
• Acute GN predominantly affects males (2:1 male-to-female ratio).
• In Port Harcourt, Nigeria, the incidence of acute GN in children aged 3-16 years
was 15.5 cases per year, with a male-to-female ratio of 1.1:1.

10. General risk factors
• Infections
• Autoimmune disorders
• Some drugs like NSAIDs, antibiotics.
• Genetic factors
• Age and gender
• Chronic diseases
• Environmental exposures

11. Etiology
• In the majority of cases of
glomerulonephritis the etiology is
unknown.
• Known etiological factors for
glomerulonephritis include:
• 1.bacteria: Staphylococcus spp,
streptococci, Treponema pallidum
2. viruses: Coxsackie virus, EBV, hepatitis B
virus, measles, mumps.
3. parasites: Schistosoma spp
• 4. drugs: penicillamine.
• 5. Endogenous substance: DNA,
tumour antigens.
• 6. Secondary glomerulonephritides
are due to other systemic diseases
e.g SLE, diabetes, amyloidosis, PAN,
Henoch-Scholein purpura
• 7. Hereditary causes: Alport
syndrome, thin basement membrane
disease, fabry disease.

12. PATHOGENESIS OF GLOMERULAR INJURY
• Immune mechanisms are responsible for most of primary
glomerulonephritides and many of the secondary glomerular disorders
• Specific mechanisms involved in glomerular injury include
1. Antibody-Mediated Injury
a) In situ immune complex deposition
b) Circulating immune complex deposition
2. Cytotoxic Antibodies
3. Cell-Mediated Immune Injury
4. Activation of Alternative Complement Pathway

14. Morphology – Histological Alterations
Glomerulonephritis/glomerulopathies may show one or more of four
basic histological changes namely:
1) Increased cellularity
2) Basement membrane thickening
3) Hyalinization
4) Sclerosis
• Histological changes are further classified into diffuse, global, focal,
segmental and mesangial.

15. Clinical manifestations of GN

16. A. Nephrotic Syndrome: Massive (>3.5 g/day) proteinuria,
hypoalbuminemia, hypogammaglobulinaemia, hyperlipidemia and
hypercholesterolaemia, lipiduria, hypercoagulable state
B. Nephritic Syndrome: Limited Proteinuria (< 3.5g/day), Hematuria,
azotemia, proteinuria, oliguria, edema, and hypertension. Biopsy
reveals hypercelluar, inflamed glomeruli

17. Classification of Glomerulonephritides
According to Aetiology
A. Primary Glomerulonephritides : these are disorders in which the
kidney is the only or predominant organ involved.
B. Systemic diseases with Glomerular involvement (Secondary
Glomerulonephritides)
C. Hereditary disorders

19. Classification of Glomerulonephritides
According to Glomerular Syndromes

21. Nephrotic syndrome
• Characterized by
• massive proteinuria >3.5g daily
• Hypoalbuminemia>3g/dl
• Generalized edema
• Hyperlipidemia and lipiduria
• Usually seen in MCD, MGN, FSGN
• Usually non proliferative.

22. A. Glomerulonephritides causing Nephrotic
Syndrome
• Minimal Change Disease
• Focal Segmental Glomerulosclerosis
• Membranous Nephropathy
• Membranoproliferative Glomerulonephritis
• Diabetes
• Amyloidosis

23. MINIMAL CHANGE DISEASE
• It is the most frequent cause of nephrotic syndrome in children.
• Characterised by diffuse effacement of foot processes of epithelial cells.
• Appears normal under light microscopy, hence called ‘minimal’. Also ‘nill
disease’
• It follows a respiratory tract infection
• Great response to corticosteroids therapy.
• The cytoplasm of epithelial cells lining the proximal tubules contains lipid
vacuoles and glassy (hyaline) protein droplets. These are due to the tubular
reabsorption of lipoproteins passing through damaged glomeruli.

24. MINIMAL-CHANGE DISEASE
Etiology and Pathogenesis
• The etiology of MCD is unknown, but there are proofs that it has immunologic
basis.
• MCD involves some immune dysfunction that results in the elaboration of a
cytokine that damages visceral epithelial cells and cause proteinuria.
• There are suggestions of loss of glomerular polyanions, hence a charge barrier
defect.

25. MINIMAL-CHANGE DISEASE
Morphology
Gross
• Kidneys are mildly enlarged with smooth capsular surface.
• Cut section shows pale to yellow cortex.
Light Microscopy
• Glomeruli: Appear normal by light microscopy.
Electron Microscopy
• GBM appears normal without any electron-dense deposit.
• Changes in the visceral epithelial cells: Most characteristic feature is uniform and diffuse
effacement of foot processes in the visceral epithelial cells.
Immunofluorescence
• Does not show immunoglobulin or complement deposits

26. MINIMAL-CHANGE DISEASE

27. MINIMAL-CHANGE DISEASE
Clinical Features
• Classically it present as nephrotic syndrome.
• Proteinuria usually is highly selective (albumin more than globulins).
• Other features: Generalized edema, hypoalbuminemia, and
hyperlipidemia.

28. FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)
• Most common cause of nephrotic syndrome in Hispanics and African
Americans
• Focal and segmental sclerosis on H&E stain
• Diffuse Effacement of foot processes on EM
• No immune complex deposits; negative Immunofluorescence
• Poor response to steroids; progresses to chronic renal failure

29. FOCAL SEGMENTAL GLOMERULOSCLEROSIS
Pathogenesis
• Primary (idiopathic).
• Secondary:
• Viruses: e.g. HIV infection
• Drugs: e.g. Heroin addiction
• Sickle-cell disease
• Massive obesity
• Congenital (e.g. unilateral agenesis) and
• acquired (e.g. reflux nephropathy)

30. FOCAL SEGMENTAL GLOMERULOSCLEROSIS
Morphology
• Light Microscopy
The focal and segmental lesions involve only a minority of the glomeruli. The
glomerular shows hyalinosis and sclerosis.
• Hyalinosis: It is characterized by extracellular accumulation of homogeneous and
eosinophilic material in the glomeruli. It represents leaked plasma proteins due to
endothelial or capillary wall injury.
• Sclerosis: It is an extracellular accumulation of collagenous matrix in the mesangium
or in the capillary loops, or both.
• Severe hyalinosis and sclerosis occludes the capillary lumens in affected glomerular
tuft leading to fibrous adhesions between the sclerotic portions of glomeruli and the
nearby parietal epithelium.
• Glomeruli, which do not show segmental lesions appear normal on light microscopy.

32. FOCAL SEGMENTAL GLOMERULOSCLEROSIS
Electron Microscopy
• Both sclerotic and nonsclerotic areas show diffuse effacement of foot
processes.
Immunofluorescence Microscopy
• IgM and C3 may be seen in the sclerotic areas and/or in the mesangium
Clinical Course
• Focal segmental glomerulosclerosis manifest as nephrotic syndrome.
• Prognosis: Children have better prognosis than adults.

33. Nephritic syndrome
• Seen in most proliferative types of Glomerulonephritis such as
postinfectious glomerulonephritis, Crescentic GN
• Its caused by glomerular cell proliferation, and inflammatory leucocyte
infiltration which injures the capillary walls and allows blood, proteins to
enter into urine which induces hemodynamic changes that decreases GFR.
• It's characterized by hematuria, azotemia, mild to moderate hypertension,
oliguria. They may also present with proteinuria and edema.

34. B. Glomerulonephritides causing Nephritic
Syndrome
I. Acute Proliferative (Poststreptococcal, Postinfectious)
Glomerulonephritis)
II. Nonstreptococcal Acute Glomerulonephritis (Postinfectious
Glomerulonephritis)
III. Rapidly Progressive (Crescentic) Glomerulonephritis
IV. IgA Nephropathy (Berger Disease)
V. Alport Syndrome

35. I.) Acute Proliferative Glomerulonephritis
These are immune complexes mediated diseases. The inciting antigen may
be
Exogenous: e.g. postinfectious glomerulonephritis, which commonly follows
streptococcal infection.
Endogenous: e.g. systemic lupus erythematosus (SLE).
Characterized histologically by diffuse proliferation of glomerular cells, and
infiltration by leukocytes (Diffuse Proliferative Glomerulonephritis)

36. Ia.) Poststreptococcal (postinfectious)
glomerulonephritis
• Etiology and pathogenesis
• Nephritic syndrome that arises alter group A beta-hemolytic
streptococcal infection of the skin (impetigo) or pharynx
• Occurs with nephritogenic strains (which carry the M protein
virulence factor)
• Usually seen in children, but may occur in adults
• Hypercellular, inflamed glomeruli on H&E
• Mediated by immune complex deposition: subepithelial 'humps' on
EM

37. Ia.) Poststreptococcal (postinfectious)
glomerulonephritis (cont.d)
Mechanism of Damage
• Immune complexes are formed in the circulation and gets deposited
within glomeruli.
• These immune complexes initiate inflammation by activating
complement and other humoral and cellular mediators of inflammation.
• The inflammatory mediators attract and activate neutrophils and
monocytes and stimulate proliferation of mesangial and endothelial cell.
• The result is a hypercellular glomerulus.

38. Ia.) Poststreptococcal (postinfectious) glomerulonephritis
Morphology
Microscopy
i. Glomeruli:
Enlarged hypercellular glomerulus: It is the classical diagnostic feature, which is seen in
all glomeruli (hence called diffuse proliferative glomerulonephritis). The hypercellularity
is due to:
Infiltration by leukocytes: It includes both neutrophils and monocytes.
Proliferation and swelling of endothelial and mesangial cells.
Rarely proliferation of parietal cells lining Bowman’s capsule: It forms crescent.
Presence of crescents is a poor prognostic feature
Obliteration of glomerular capillary lumen: It is due to swelling and proliferation of
endothelial and mesangial cells + infiltration by leukocytes.

41. Ib.) Nonstreptococcal Acute Glomerulonephritis
(Postinfectious Glomerulonephritis)
Acute proliferative glomerulonephritis may also occur in association
with other infections:
• Bacteria: Examples, staphylococcal endocarditis, pneumococcal
pneumonia, and meningococcemia.
• Virus: Examples, hepatitis (B and C), mumps, HIV infection, varicella,
and infectious mononucleosis.
• Parasite: Examples, malaria, toxoplasmosis.
The morphological changes are similar to poststreptococcal
glomerulonephritis.

42. Rapidly Progressive (Crescentic)
Glomerulonephritis
• If not treated, death occurs due to renal failure within weeks to months.
• RPGN is classified into three types based on immunological findings. Each
type may be idiopathic or associated with a known disorder.
• Type I
• Type II
• Type III
• It is a syndrome that progresses to renal failure in weeks to months
associated with severe oliguria and signs of nephritic syndrome.
• Characterized by crescents in Bowman space (of glomeruli) on H&E
stain; crescents are comprised of fibrin and macrophages.

44. 2. Rapidly Progressive (Crescentic) Glomerulonephritis .d
GOODPASTURE SYNDROME
• In Goodpasture syndrome, anti-GBM antibodies cross-react with pulmonary
alveolar basement membranes causing pulmonary hemorrhage associated with
acute renal failure
Pathogenesis
• High prevalence of certain HLA subtypes (e.g. HLA-DRB1) in these patients point
towards genetic predisposition to autoimmunity.
• Anti-GBM antibodies are formed against Goodpasture antigen. This antigen
results from conformational changes in the alpha-3 chain of type IV collagen of
GBM.
• Anti-GBM antibodies cross react with the target antigen, which is also
expressed on pulmonary alveolar capillary basement membranes. This results in
pulmonary hemorrhages and hemoptysis, which may be life threatening.

45. 2. Rapidly Progressive (Crescentic) Glomerulonephritis
GOODPASTURE SYNDROME
Microscopy
• Glomeruli: Its characteristic feature is crescents in most of the
glomeruli. Hence, the term crescentic glomerulonephritis.
• Crescents Components: Crescents are formed by;
Proliferation of the parietal epithelial cells lining Bowman capsule
Infiltration of monocytes and macrophages into the urinary space.
Stimulus: Fibrin leaked into the Bowman space is the stimulus and is found
between the cellular layers. Fibrin is derived from fibrinogen, which escaped
through the ruptured GBM into Bowman space.

47. 2. Rapidly Progressive (Crescentic) Glomerulonephritis
GOODPASTURE SYNDROME
Immunofluorescence Microscopy
• Goodpasture syndrome show linear GBM fluorescence for IgG and C3
complement.
Electron Microscopy
• Ruptures in the GBM: It allows leukocytes, proteins, and
inflammatory mediators to leak into the bowman space and initiates
crescent formation.

48. CHRONIC GLOMERULONEPHRITIS
• Chronic glomerulonephritis is an end-
stage of many types of
glomerulonephritis
Morphology
Gross:
• Both kidneys are symmetrically
contracted and show diffusely granular
cortical surfaces and symmetrical
contraction.
• Cut section: It shows thinned cortex
and an increase in perinephric fat. The
capsule is difficult to remove because
of adhesion.

49. CHRONIC GLOMERULONEPHRITIS
Microscopy
• Glomeruli: The glomerular changes depend on the stage of the
disease:
• Early stages: It may show features of the primary disease.
• Late stages: Obliteration of glomeruli, which appear as acellular eosinophilic
masses consisting of plasma proteins, increased mesangial matrix, basement
membrane-like material, and collagen. glomeruli are completely effaced by
hyalinised connective tissue, making it impossible to identify the cause of the
antecedent lesion

52. Hereditary syndromes
Alport syndrome
• Etiology:
Defective GBM synthesis because of production of abnormalcollagen
type IV.
• Pathogenesis
The lesion so formed interfere with the structure and function of GBM.
• Clinical course:
Severe hematuria, proteinuria and rarely nephrotic syndrome develops.
Presence of auditory defect.

53. Glomerular lesions associated with systemic
diseases
Amyloidosis
• Review
SLE
• Review

54. Investigations
• The specific investigations performed may vary depending on the suspected underlying
cause and the clinical presentation of the individual.
1. Urine test
• Urinalysis, urine mcs
2. Blood test
• Kidney function test
• Complete blood count
• Autoimmune and infectious disease markers
3. Imaging studies
• Renal ultrasound
• Renal biopsy

55. Conclusion
• Glomerulonephritides are a common cause of mortality well
distributed in people of all ages and sexes.
• They are suspected when an individual presents with any of their
clinical manifestations (nephritic and nephrotic syndrome)
• It is important to know their diagnosis and mechanism of action.

56. THANK YOU!

57. References
• Robbins and Cotran Pathologic Basis of Disease by Kumar et al. 9th
Edition
• Path to pathology