this poerpoint includes introduction to kidney disorders - anatomyof kidney, histology of glomeruli , pathogenesis and pathology of glomerular disease

3.  The main purpose of the kidney is to
separate urea, mineral salts, toxins, and
other waste products from the blood.
 They also do the job of conserving water,
salts, and electrolytes.
 At least one kidney must function properly
for life to be maintained.

7. GLOMERULUS:
 Glomerular capillary wall:
1. Fenestrated endothelium –70 – 100
nm,
2. Glomerular Basement Membrane
.. Lamina rara interna,
.. Lamina densa,
.. Lamina rara externa
3. Visceral epithelial cells (podocytes)
4. Mesangial cells – contract,
proliferate, collagen & matrix,
secretion;

8. Three-dimensional schematic drawing of the glomerulus
Afferent arteriole
Efferent arteriole
Bowman’
s Capsule
Basement
membrane
Visceral
Epithelium(Podocyte)
Parietal
Epithelium
Capillary
loops
Bowman’s Space
Endothelial
cells
Stucture of renal
glomerulus
Mesangial matrix
and cell

9. Ultramicroscopic
Stucture of
glomerullar
Capillaries
Filtration
Mem

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12. Light microphotograph of
glomerulus
•Normal
celluarity
;
•Patent
capillary
lumens

14.  DISEASES OF GLOMERULI
 DISEASES OF TUBULES
 DISEASES OF INTERSTITIUM
 DISEASES OF BLOOD VESSELS

15.  AZOTEMIA – BUN, Creatinine
--- GFR
 UREMIA – Azotemia + Clinical signs and
symptoms + Biochemical abnormalities +
Involvement of G I tract, Peripheral nerves
.. and heart;

16. Glomerular disease

19.  DEFINITION
Abnormalites of glomerular funtion can be
caused by damage to the major components of the
glomerulus: Epithelium (podocytes), Basement
membrane, capillary endothelium, mesangium.
 Damage manifested by an inflammatory process.

21. Histologic alterations
a) hypercellularity:
i) cell proliferation of mesangial cells or
endothelial cells
ii) leukocyte infiltration (neutrophils,
monocytes and sometimes lymphocytes)
iii) formation of crescents
- epithelial cell proliferation (from
immune/inflammatory injury)
- fibrin thought to elicit this injury
(TNF, IL-1, IFN- are others)
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22. b) basement membrane thickening
- thickening of capillary wall
c) hyalinization (hyalinosis) and sclerosis
-accumulation of material that is
eosinophilic and homogeneous
- obliterates capillary lumen of glomerulus
(sclerotic feature)
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23. classification is based on histology.
Subdivided:
a) diffuse (all glomeruli)
b) global (entire glomerulus)
c) focal (portion of glomeruli)
d) segmental (part of each glomerulus)
e) mesangial (affecting mesangial region)
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24. What causes
glomerular disease ?
Most are of
immunologic origin, and
caused by immune
complexes !
• metabolic stress: DN
• mechanical stress:
• hypertension

25.  Antibody mediated injury
 In situ immune complex deposition
Fixed intrinsic tissue antigens
collagen type4 antigen [anti GBM-nephritis]
Heymann antigen [membranous nephropaty
Mesangial antigens
Circulating immune complex deposition
Endogenous antigen[DNA,Nuclear
proteins,immunoglobulins,igA]
Exogenous antigen [infectiousagents,drugs]
Cytotoxic antibodies
Cell mediated immune injury
Activation of alternative complement pathway

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27. Pathogenesis of Glomerular Disease
Immune mechanisms underlie most cases of
primary GN and many of the secondary cases
a) 2 forms of Ab-associated injury
i) injury resulting from soluble Ag-Ab
deposits in glomerulus
ii) injury from Ab reacting in-situ with
glomerulus
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28. • In Situ Immune Complex Deposition
a) Ab act directly with intrinsic tissue Ag
“planted” in the glomerulus from the
circulation
b) 2 forms of Ab-mediated glomerular
injury
i) anti-GBM Ab-induced nephritis
- Ab directed against fixed Ag in
ii) Heymann nephritis
- a form of membranous GN
- Ab bind along GBM in “granular
pattern”
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29. Location: Mesangial and sub-endothelial

30. Location: GBM sub-epithelial
• circulating auto antibodies with intrinsic
autoantigens (component of normal parenchyma)

31. Location: GBM sub-epithelial
Extrinsic antigens planted within the glomerulus

33. In situ immune
complex
Circulating
immune
complex
Activation of T
lymphocytes
Acitvation of complements
cytokines
C5b-9 C5a,C3a
Epithelial, mesangial,
Endothelial cells
Macrophagepolynuclear
leucocyte,
platelets
Mesangial
cells
oxidative stress, protease, matrix accumulations
Glomerular Disease

34. Glomerular Diseases
PRIMARY GLOMERULOPATHIES
Acute proliferative glomerulonephritis Post-
infectious
Rapidly progressive (crescentic) glomerulonephritis
Membranous glomerulopathy
Minimal-change disease
Focal segmental glomerulosclerosis
Membranoproliferative glomerulonephritis
IgA nephropathy
Chronic glomerulonephritis
SYSTEMIC DISEASES WITH GLOMERULAR INVOLVEMENT
Systemic lupus erythematosus
Diabetes mellitus
Amyloidosis
Goodpasture syndrome
Microscopic polyarteritis/polyangiitis
Wegener granulomatosis
Henoch-Schönlein purpura
Bacterial endocarditis
HEREDITARY DISORDERS
Alport syndrome
Thin basement membrane disease

35. Various types of glomerulopathies are
characterized by one or more of four basic
tissue reactions:
1. Hypercellularity
2. Basement membrane thickening
3. Hyalinosis
4. Sclerosis

37.  Common form of GN in developing countries.
 6 to 10yrs of age
 1 - 4 weeks after a streptococcal infection of pharynx
or skin (Impetigo)
 Group A β-haemolytic streptococci - types 12, 4, 1
 Immunologically mediated disease
 Immune Complex mediated
 Anti - endostreptosin & other cationic antigens .
 Serum – C

38. Glomeruli-
 Enlarged , hypercellular glomeruli
- infiltration by leukocytes
- proliferation of endothelial &
mesangial cells,
- crescent formation (severe cases)
- obliteration of capillary lumen
 Fibrin deposition in capillary lumen &
mesangium.
 Interstitial edema and leucocytic infiltration
 Tubules contain red cell cast.
Diffuse

39. Normal glomerulus

40. Acute
Proliferative GN

41. Acute
Proliferative GN

43. Immunofluorescence:
- granular deposits of IgG , IgM , C3 in
mesangium , along BM

44. Electron microscopy:
 Discrete , amorphous , electron dense deposits
on epithelial side of BM often having the
appearance of “humps

46.  Sudden onset in a young child - malaise,
fever , nausea , oliguria , hematuria,
 Edema , mild - moderate hypertension ,
elevation of BUN
 Urine - RBC casts, proteinuria
 Lab - antistreptococcal antibody titre ,
C3

47.  95% -- children recover,
 < 1% - rapidly progressive GN
 1-2% - slow progression to
chronic GN,
 Persistent proteinuria,
 Abnormal GFR
 Adults
Poor
prognosis

48. (Rapidly Progressive Glomerulonephritis)
[RPGN]

49.  Severe glomerular injury
 Does not denote a specific etiologic form
of GN
 Clinically - rapid & progressive loss of
renal function & death within weeks to
months
 Crescents in most glomeruli – parietal
epithelial cells proliferation;

50.  Type - I RPGN ( Anti-GBM antibody
induced disease)
.. Idiopathic,
.. Goodpasture syndrome;
 Type - II RPGN (immune Complex)
.. Idiopathic, postinfecious, SLE,
Henoch-Schonlein purpura (IgA), others;
 Type - III RPGN ( Pauci-immune )
.. ANCA associated, Idiopathic,
Wagener granulomatosis, PAN;

51.  Linear deposits of IgG , C3 in GBM
 Cross reaction with pulmonary
alveolar BM
 Good - Pasture’s antigen located in
noncollagenous portion of α3
domain of collagen type - IV

52.  Immune complex mediated disease
 Complication of immune complex nephritides
- Post infectious GN , SLE , IgA nephropathy
 Granular deposit of immune complexess of
IgG and C3 along glomerular capillary walls.
 IF - lumpy bumpy granular pattern

53.  Lack of anti GBM antibody , immune
complexes by IF , EM
 ANCA present- defect in humoral immunity.
 Usually a component of systemic vasculitis -
Wegeners Granulomatosis , Polyarteritis
 Idiopathic

54.  Gross :
Kidneys enlarged , pale ,smooth
outer surface.
C/S petechial hemorrhages on
cortical surface

55.  Crescents
proliferation of parietal cells migration of
monocytes ,macrophages into Bowmans space
 Crescents obliterate Bowman’s space ,
compress glomerular tuft
 Fibrin strands are prominent between cellular
layers in the cresents.

58.  Crescents Sclerosis
 EM : subepithelial deposits
ruptures in GBM
 IF : Postinfectious cases - granular
Good Pastures syndrome - linear
Idiopathic - granular / linear

59. Electron micrograph showing characteristic wrinkling of GBM
with focal disruptions (arrows).

61.  Hematuria , RBC casts , proteinuria
 Hypertension , Edema
 Good - Pastures syndrome -
Hemoptysis
 Anti - GBM , antinuclear , ANCA
 Renal involvement - progressive

62.  a) massive proteinuria (> 3.5 g/day)
 b) hypoalbuminemia
 c) generalized edema
 d) hyperlipidemia and lipiduria

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64. Latent GN
(asymptomatic
urinary
abnormalities)
Nephrotic
syndrome
Acute GN RPGN Chronic GN
microscopic or
Macroscopic
hematuria
Proteinuria
Dysmorphic
Glomerular
erythrocytes
Proteinuria>3.5g/d
Hypoalbuminemia
Hyperlipidemia
Edema
Hematuria
Proteinuria
(1-3g/d)
ARF
Edema
Hypertension
Red cell casts
•Rapidly
deterioration of
renal function
•Hematuria,
Proteinuria
• oliguria or
anuria
Red cell casts
•With or
without
systemic
symptom
•Hematuria
Proteinuria
•Hypertens
on
•Reduced
GFR