glommerulo disease

1. Glomerular diseases

2. Glomerular diseases (glomerulopathy)
 heterogeneous group of diseases
Dividing:
a) Primary glomerulopathy
b) Secondary glomerulopathy
c) Hereditary glomerulopathy
– can be manifestation of systemic diseases, vascular, metabolic or
genetic disorders affecting also other organs
The mechanisms for glomerular injury are complex

more often are iniciated by an immune response
exclude

3. • A group of diseases:
pathological changes:glomerular
injury
clinical manifestation:protenuria/
hematuria
complicated causes/mechanisms
various clinical manifestation
different prognosis
multiple treatment

4. What kind of nephritis does Alport syndrome belong to？
1 Primary glomerular diseases
2 Secondary glomerular diseases
3 Hereditary glomerular diseases

5. Drugs and poisons product of metabolism
Special capillary bulb structure
The renal blood supply is abundant
Vasculitis

6. Clinical manifestation of GN
initiation hematuria proteinuria Edema,hyp
ertention
Renal
failure
Acute GN acute 100% 100% frequent resumable
rapid
progressive
GN
acute 100% 100% frequent ARF
Chronic GN latent frequent frequent frequent CRF
Latent GN latent frequent <1g/d - -
Nephrotic syntrome

7. Diffuse
Membranous nephropathy
proliferative glomerulonephritis
Sclerosing glomerulonephritis
Mesangial proliferative
glomerulonephritis
endocapillary proliferative
glomerulonephritis
Mesangial capillary
glomerulonephritis
Crescentic and necrotizing
glomerulonephritis
Minor glomerular abnormalities
Focal segmental lesions

8. Fig. Glomerular basement membrane (GBM)
negative charge barrier
Immunopathologic mechanisms

9. Immunopathologic mechanisms
Damage of kidney depend on:
- mechanism and intensity of immune reaction
- collocation of antigens (Ag)
Mechanisms:
 Damage by immunocomplexes
 Damage by cytotoxic antibodies (Ab)
 Cell-mediated immune injury = delayed-type
hypersensitivity
 Damage by complement and proinflammatory mediators

10. Cytotoxic (Type II) reaction
– antibody mediated cytotoxicity (ADCC)
These occur when antibodies interact
with antigens found on cell
surface
2 mechanisms of cytotoxicity:
1. Ab mediate cell destruction
via mechanism ADCC (cell
cytotoxicity dependent on Ab)
2. Ab directed against cell-
surface antigens mediate cell
destruction via complement
activation

11. Type III reaction – immune complex-
mediated hypersensitivity
- The reaction of antibody with
antigen generates immune
complexes. In some cases, large
amounts of immune complexes can
lead to tissue damage
They deposited in various
tissues

induce complement activation
and ensuing inflammatory response
Antigens can be:
a) Endogenous – for example DNA in
SLE
b) Exogenous – bacteria, viral,
parasitical Ag

12. The magnitude of the reaction depends on the quantitity of immune
complexes as well as distribution within the wall of glomerular capillary

13. Location of immune deposits in the glomerular capillary wall

14. Delayed – type hypersensitivity (Type IV)
T lymphocytes may also recognize
antigen
When they do, a mononuclear cell
infiltrate may accumulate at the
site of Ag concentration and
lead to the elaboration of toxic
products and tissue injury

15. Immune
mechanisms
Humoral
Cell mediated
Non immune
mechanisms
inflammation
Glomerular diseases

16. • Immune mechanisms
deposits of immuno- complex(IC)
antigen+antibody
kidney deposits

17. • Extrinsic
drug:nonhomologous serum,penicilin
Foods:xenogenic protein
Pathogens:specific serotypes streptococci,HBV,HCV
• Intrinsic
Nucleus(SLE)
Cytoplasm(ANCA)
Cellular membrane
Antigen of tumor
Antigen of thyroid

18. Why does IC deposit in the glomeruli
• Large area of glomurular capallaries
More chances of contact
• Net structure of CIC
Easy to deposit and settle down
• Decrease clearance of CIC
clearance dysfunction of mesangial cells
Disability of mononuclear macrophage
Component or function defect of complements

19. Balance of deposit and clearance of IC
determines thd situation of the diseases
• Persistence of antigen
• Clearance dysfunction of mesangial cells
• Disability of mononuclear macrophage
• Component or function defect of
complements
IC deposit>clearance

20. • Non immune mechanisms
Glomerular hypertension
Hyperlipidemia(LDL-Cho)
Advanced glycosylation end products
protein
glomerulosclerosis

21. inflammation
• Mediators of inflammation
A group of molecules which act as mediators of
inflammation and complicated biological function
• Original mediators in kidney
Extrinsic cells in kidney
Infiltrative neutrophil,lymphocyte,mononuclear
macrophage,platelet
intrinsic cells in kidney
Mesangial cells,tubular cells,endothelial cells

22. Mediators of inflammation
• Active oxygen and active nitrogen
• Lipids
• Complements
• Cytokines
• Adhension molecules
• Growth factors
• Vasoactive substances

23. Effects of inflammation
mediators
• To arouse or promote
Proliferation of cells
Accumulation of extracellular matrix
Changes of histological structure
Expression of immunomodulating
molecules and adhension molecules

24. Mechanism of primary GN
Immune
Mesangial cells,tubular
cells,endothelial cells
Essential in the initiation
Essential in the progressive period
inflammation
Inflammation cells
Extrinsic cells Intrinsic cells
Infiltrative
neutrophil,lymphocyte,mononucl
ear macrophage,platelet
Inflammation mediators
Active oxygen and active nitrogen,cytokines,growth factors,chemotatic factors,
complments,vasoactive subtances,coagulation and fibrolysis system,enzyme
Glomerular injuries
Non immune

25. Sites of pathological changes
• Mesangium
mesangial cell
mesangial matrix
• Basement membrane
Podocyte
Endothelial cell

26. Pathogenesis
Normal glomerular structure
• Glomerular tuft composed 4 major components
– Endothelial cells
– Visceral epithelial cells or Podocytes
– Mesangium
– Capillary loop basementmembrane
• Capillary wall
– carries a net negative charge
– acts as both
– charge-selective
– size-selective filter

27. Glomerular capillary wall:
Size selective filter
The capillary wall restricts the passage of large molecules into Bowman's space, while
there is less restriction of smaller molecules.
As radii increase, filtration decreases, approaching zero at radii > 4.2 nm

28. Glomerular capillary wall:
Charge-Selective Filter
The capillary wall restricts the passage of negatively charged molecules such as albumin
while neutral substances pass more freely and are restricted by size from passing into
Bowman's space.

29. Pathological changes
• LM
Mesangial cells,matrix of mesangium
Endothelial cells
Epithelial cells
Basement membrane
Loops of glomeruli
• EM（Electron microscope）
• Foot process
Basement membrane
Hyperplasy of mesangium(electron dense deposits)
• IF
Sites,appearances,type of deposits（IG or C）

30. Basical changes
• Proliferation
• Fibrosis and sclerosis
• Necrosis
• Infiltration of inflammation cells

31. Extents of injury
• Primary GN:glomerular injury-only or dominating
injury
• Secondary GN: glomerular injury-a part of systematic
diseases
• Diffuse:impaired glomeruli>50%
• Focal: impaired glomeruli>50%
• Global:impaired capillary loops of a glomerule>50%
• Segmental:impaired capillary loops of a
glomerule<50%

32. Pathological types of primary
GN
• Minimal change of glomerulonephritis
• Focal segmental lesions
• Diffuse glomerulonephritis
• Unclassified glomerulonephritis

33. Minimal Change Disease (MCD)
• Most common cause of nephrotic syndrome in childhood
– In a prospective study of untreated children with N.S.:
• minimal change disease was found in 76.6%.
• Only 10% to 30% of adult cases of nephrotic syndrome
– Percentages vary in different parts of the world
• The clinical onset of nephrotic syndrome associated with:
– upper respiratory infection
– with routine prophylactic immunizations
– Other genetic and environmental factors may also be
important

34. Morphologic Features (LM & IF)
• LM: normal in glomeruli, tubules and interstitium
• IF: No immune deposits

35. • diffuse effacement of the epithelial cell (podocyte) foot processes
Morphologic Features (EM)

36. Clinical Course
• Most patients with MCD develop mild periorbital edema as
initial complaint
• Proteinuria: to be "selective“
– primarily of albumin
– Microscopic hematuria is rare (13 to 36%)
– Hypertension: also unusual
• Treatment:
– Most patients (90%) respond to an 8 week course of steroids
– Cytotoxic agents: may be used in steroid resistant cases (~10%)
– Renal failure: rare
– Relapses are common

37. Focal Segmental Glomerulosclerosis
(FSGS)
(a ) often present with severe proteinuria
(b ) 30-50% combine with hypertension
(c ) HIV may associated with FSGS
(d ) subepithelial “ hump” of glomuerulus in
electron microscopy

38. Focal Segmental Glomerulosclerosis
(FSGS)
• Prevalence in idiopathic nephrotic syndrome :
– 10% of childhood
– 15-20% of cases of adult
• Symptoms and signs: common with
– proteinuria
– microscopic hematuria
– Hypertension
• Pathogenesis:
– sclerosing lesions and their progressive nature are debated
• hyperfiltration,
• increased intracapillary glomerular pressure

39. Morphologic Features
• LM: focal and segmental glomerular sclerosis with capillary loop collapse, hyaline and
lipid deposition and often adhesion to Bowman's capsule
– The remainder of the glomerular tuft is normal in appearance; thus the term 'segmental'.
The lesions are considered to begin or to be more common near the corticomedullary
junction.
• IF: Deposition of IgM and C3 in the mesangium or in the areas of segmental sclerosis
may be seen, but no immune complex deposition is present.
• EM: effacement of podocyte foot processes. Podocyte denudation may be present
focally as an early lesion, and segmental sclerosis may also be seen

40. Clinical Course
• FSGS may be :
– primary (idiopathic)
– secondary to a number of etiologic agent :
• Unilateral renal agenesis
• Renal ablation
• Sickle cell disease
• Morbid obesity (with or without sleep apnea)
• Congenital cyanotic heart disease
• Heroin nephropathy
• HIV nephropathy
• Aging kidney

41. Membranous Glomerulonephritis（MGN）
• Antibody mediated disease
– ICs localize to subepithelial of the capillary
loop
• between outer aspect of GBM and podocyte
• Immune complexes
– develop in situ
– deposition of circulating ICs (less likely)
– antibody may bind to
• intrinsic glomerular antigen
• exogenous antigen planted on the capillary wall
– Serum complement level was normal

42. Clinical Manifestation
• more common in adults (peak 40-50 y/o)
• mostly older than 30 years at diagnosis
• 35-50% of cases of adult nephrotic
syndrome
• Most patients present with:
– heavy proteinuria: most commonly in nephrotic
range
– insidious in onset
– few patients accompanying microscopic
hematuria

43. Morphologic Features
Capillary walls are thickened and numerous subepithelial "spikes" are
present on capillaries of this glomerulus, representing elaboration of
basement membrane between subepithelial immune deposits.
LM

44. Immunofluorescence
Microscopy
Direct immunofluorescence microscopy of frozen tissue demonstrates
bright granular staining of the subepithelial aspect of the capillary
loops with antibody to IgG

45. Electromicroscopy
Ultrastructurally numerous subepithelial electron dense deposits are
present. The deposits are separated by basement membrane
correlating with the "spikes" seen by light microscopy.

46. Membranoproliferative Glomerulonephritis
(MPGN) (mesangiocapillary glomerulonephritis)
• Chronic progressive glomerulonephritis
– occurs in older children and adults
• Circulating immune complexes (CIC)
have been identified in 50% of patients
• activation of the complement system
with hypocomplementemia, is a
hallmark of MPGN.

47. MPGN (IF)
Type I: subendothelial and mesangial deposits of IgG and C3

48. MPGN (EM)
Electron microscopy
Electron microscopy
Type I: deposits in subendothelial and mesangial
Duplication of the capillary loop basement membrane between the
deposits and interposed mesangium, and the endothelial cells.

49. Clinical Course of MPGN
Clinical manifestation:
• Nephrotic syndrome
• Abnormal urinary sediment with non-
nephrotic proteinuria
• Acute nephritis
• Lab. Data:
– depressed serum complement levels

50. In summary
• Proliferation of mesangium can presents in various
types of GN
• Proliferation and subsequent stiffness of mesangium
may be the results of various types of GN
• FSGS:primary—later phase of the disease itself
secondary—later phase of other type of GN
• Crescents can presents in different types of GN

51. Clinical menifestation
• Proteinuria
Urinary protein test—positive
Urinary protein excretion
rate>150mg/24h

52. • Quantity:
• Mild:<1.5g/d
• Moderate:1.5-3.5g/d
• Severe:>3.5g/d

53. • Hematuria
RBC>3/HP(fresh,10ml/sample,1500rmp
centrifuge for 5min,sediment observation)
• Gross hematuria
Red color of urine,1ml blood/1L urine

54. RBC from glomeruli
Squeezing through
GBM
Changing when passing tubule
with different osmosis
Dismorphic RBC
Phase contrast
microscopy
Dismorphic
RBC>50%,hypothesis
of glomerular bleeding
Dismorphic
RBC>50%,final
diagnosis of
glomerular bleeding
Urinary RBC volume distribution curve
Dissymmetry curve
MCV of urinary
RBC<that in blood

55. edema
Glomerular diseases
GFR↓
Intrinsic RAS or
aldosterone↑
Water sodium filtration↓
Water sodium readsorpation↑
Primary Water and sodium
retention
Effective circulation
blood volumn↑
edma
Effective circulation blood volumn↓
Large ammount of
urinaryprotein lost
hypoalbuminemia
Colloid osmotic
pressure↓
secondary water and
sodium retention

56. hypertention
Glomerular diseases
Primary Water and sodium
retention
Volumn dependent
hypertension
Stimulus,such as ischemia
Vessoconstrictive
substances↑ RAS ALD
Vessoactive substances
dependent
Vessodilatory
substances↓ PGI2,PGE2

57. Clinical types of GN
• Glomerulonephropathy
Confined concept
Leading manifestation: proteinuria /hematuria
Extensive concept
Glomerular diseases
• Glomerulonephritis
Leading manifestation:hematuria /proteinuria

58. Clinical manifestation of GN
initiation hematuria proteinuria Edema,hyp
ertention
Renal
failure
Acute GN acute 100% 100% frequent resumable
rapid
progressive
GN
acute 100% 100% frequent ARF
Chronic GN latent frequent frequent frequent CRF
Latent GN latent frequent <1g/d - -

59. Acute glomerulonepritis
• Etiology:streptococcus
others:bacteria
viruses
parasites
• antigen:components of cytoplasm/
membrane
• frequently CIC
•

60. Pathological changes
• Endocapillary proliferative GN
Acute phase
Proliferation of endothelial
/mesangium
Recovery phase
Only mesangium
proliferation,sometimes minor injure

61. Clinical manifestation
• Epidemiology:primarily children,sometimes
adult/aged
• Preliminary infection
Frequently tonsillitis,upper respiratory
infection
• Latent period:1-3w
Occasionally skin infection
Latent period:longer,less than 4w

62. Nephritis syndrome
• Hematuria:100%,40% are gross
hematuria
• Proteinuria:frequently,<20% are NS
• Edema:>90%
• Hypertension:80%
• Renal failure:mild,ARF

63. Laboratory finding
• Acute phase of infection of strep.
Elevated ASO titer
Only the marker of infection,not
nephritis
• Acute phase of immune reaction
Serum C3/total complement↓,return
normal within 8w
Blood CIC↑

64. Natural history
• Edema and hypertention
Disappear in one month
• Hematuria,proteinuria
Usually reduce in one month,resolve in2-
3 months
Some resolve in 6-8 months
• C3:return to normal in two months

65. diagnosis
• Points:
• Preliminary infection/latent period
• Acute onset
• Surely hematuria,frequently edema and
hypertention
• ASO↑c3↓--dynamic change
• Self limitation

66. Indications of renal biopsy
• Oligouria>1w,except
ECBV,insufficient,urinary tract
obstruction,etc
• Progressive renal failure
Unresolved in 2 months
Untypical manifestation,or with NS

67. treatment
• Supportive treatment
• Rest
• Food and water
• Restrictive intake of NaCL<5g/d
If moderate to severe edema or hypertention
• Water
If decreased urine volumn
• Protein
Renal failure,but not dialysis yet

68. Treatment of infection
• Penicilin for 2w
• Tonsillectomy if recurrent attacks of tonsillitis
• Patient is stable:U pro<1g/d,Urbc<10/HP
• Penicilin for 2w before and after the surgery
• Symptomatic treatment
Diuresis
Antihypertention
dialysis

69. prognosis
• Hematuria,proteinuria
Usually reduce in one month,resolve in
2-3 months
Some resolve in 6-12months
• 1% ARF death
• 6-18% CGN?

70. Rapidly progressive glumerulonephritis
• Rapidly progressive glumerulonephritis
syndrome
• Some induced by respiratory infection
• Acute onset,rapidly progressive
• Renal failure within a few weeks to a few
months

71. • Primary RPGN:crescentic GN
• Other primary GN:other pathological
changes with lots of crescents
• Secondary RPGN:SLE,SHP,etc

72. Type 1
Anti GBM
Type 2
IC
Type 3
Pauci-immune
Linear GBM
deposits
Granular
GBM/mesangium
deposits
-
Anti-GBM+ C3↓CIC↑ 70-80%small
vessel ANCA+
The
young/middle
aged
The middle
aged/aged
The middle
aged/aged

73. diagnosis
• Acute onset
• Rapidly progressive
• Renal failure within a few weeks to a few
months
• Acute renal failure-chronic renal failure

74. Treatment-early!!!
• Aim to humoral immune mechanism
• Plasmapheresis discard the antibodies
plasm exchange immoadsorption,type1
typ2
• Drugs:glucocorticoid+cytotoxic drugs
MP05.-1.0g/d,repeat if necessary
CTX
type2-type3

75. Symptomatic treatment
• Renal failure
Balance of fluid,electrolytes and acid
base
Dialysis
• Infection
• hypertension

76. prognosis
• Hardly relieve
• Mostly CRF-death
• Risk factors:type1 worst,type2 worse,type
3 bad
Treatment:not
progressive,not prompt
Age:the aged

77. Chronic glomerulonephritis
• Clinical manifestation:chronic nephritis
syndrome
• Pathological change:except
MCD,MmRPN,crescentic GN

78. Clinical manifestation
• Age:any age,frequently young
• Priliminary infection:upper respiratory
infection,intestinal tract,latent period<1w
• Nephritis syndrome:
Hematuria,proteinuria,edema
hypertention,Renal failure
uremia

79. Prognosis factor
• Pathological properties
• Treatment
• Hypertension
• Infection,prerenal factors(hypertension etc)
• Nephrotoxic drugs

80. Point of diagnosis
• Chronic onset
• proteinuria and/or hematuria
• Protracted and progressive

81. AGN CGN
age children Young/middle-aged
Preliminary
infection
frequently sometimes
Latent period 1-3w <1w
onset acute Chronic,insidious
hematuria 100% Sometimes no
edema frequently Sometimes no
hypertension frequently Sometimes no
ASO frequently↑ normal
Blood C3 ↓,<8W persistent↓/normal
prognosis <1y protracted and

82. Secondary GN
• SLE:sysmetic presentation
Immune abnormality
Pathological changes

83. Treatment
• Target Inhibit immune reaction
Halt the progression of disease
• Restrictive intake of protein
<0.5-0.8g/kg/d
Protein of high biological value
↓Pressure in glomeruli

84. antihypertention
• Less than 140/90mmHg
Ideal target125/83mmHg
• ACEI/ARB:dialation of efferent glomerular
Arteriole>dialation fo afferent
Pressure in glomeruli↓
Upro↓
Postpone glomerulosclerosis

85. • Antiplatelet
• Immunosuppression
• Glucocorticoid

86. Four major pathogenetic forms of glomerular
injury
In non-proliferative glomerulopathy:
 Damage by antibodies
 Damage mediate by complement
In proliferative glomerulopathy:
 Damage by circulating proinflammatory cells (especially
neutrophils and macrophages)
 Damage by localy activating resident cells (for example
mesangial cells)

87. Classification of glomerulopathies
• Clinical: primary x secondary
• According time period: acute x subacute x chronic
• According renal biopsy: focal x segmental x diffuse
• According number of cells: non-proliferative x
proliferative
• According imunofluorescence:

88. Pathogenic mechanisms of glomerular diseases
 NEPHRITIC
NEPHROTIC
Chronic
glomerulonephritis

89. Pathogenesis of nephritic diseases

90. Histologic pattern
• May not correlate with
the clinical presentation
• Various histological
types of
glomerulonephritis

91. B: “Minimal changes” GN = lipoid nephrosis: some mesangial proliferation,
edematous podocytes, fusion (“loss”) of their foot processes
C: Intracapillary mesangial proliferative GN: proliferation of endothelia and
mesangium, peeling off of enthelial cells from the GBM, duplication of GBM,
“humps” formed by immunocomplexes
D: Crescentic GN: proliferation of all components (aggressive white cells, endo-
and epithelia, mesangium, epitheloid and giant cells), leakage of fibrin.
Hypersensitivity reaction type II or IV
E: Membranous GN: Precipitation of immunoglobulins on the outer surface of the
GBM (“spikes”  complete incorporation of Ig into the membrane)
F: Proliferative sclerotizing GN: advanced mesangial proliferation  narrowing
and destruction of capillaries

92. Acute glomerulonephritis (poststreptococcal
GN)
 Is commonly caused by infection by certain
strains of group A beta-hemolytic
Streptococci (pharyngitis, pyoderma)

Ab against streptococci react with vimentin
 imunokomplexes
 nephritis develop after a latent period of
about 2-3 weeks
 Clinical syndrome: nephritic syndrom
 Histologic pattern: intracapillary
proliferation of mesangial and endothelial
cells with subepithelial („humps“) and
subendothelial deposits (C3, or IgG)
Acute diffuse proliferative GN

94. Postinfectional non-streptococcus
glomerulonephritis
 Acute glomerulonephritis can develope also in the course of other infections:
- stafylococci - herpes virus
- pneumococci - EBV
- Klebsiella pneumonie - virus hepatitis B
 GN in infection endocarditis
 GN in visceral abscessus (especially lung)
Histologic pattern and clinical syndrome – similar one as in poststreptococcal GN

95. Focal proliferative glomerulonephritis
- different etiology:
 IgA nefropathy
 Nephritis in systemic lupus erythematodes (SLE)
 Nephritis in bacterial endocarditis
 Henoch-Schölein purpura

96. Rapidly progressive glomerulonephritis
(RPGN)
 Heterogeneous group of diseases, it is characterised by intense proliferation
of glomerular/capsular epithelial cells in the form of a crescent.
 crescemt = accumulation and proliferation of extracapillary cells.
 The glomerular capillaries collapse and are bloodless, and fibrin can be
identified within the capsule

it can stimulate proliferation of parietal epithelial cells

deposits of fibrin compress the glomerula capillaries tuft
( GFR and destruction of glomerulus)

97. Three forms of RPGN
 GN with creation of antiobdies (IgG, IgA) agains
GBM (anti-GBM)
- linear deposits of Ig
(+ alveolocapillary BM) Goodpastures´ syndrome
 GN with granular deposits of Ig and complemen
- formation of crescent is complication less serious
intracapillary proliferative GN (IgA nefropathy, SLE,
acute GN e.g.)
 GN with ANCA antibodies
- ANCA ab (Ab agains cytoplasma of neutrophiles)
2 forms – systemic disorders
(Wegener granulomatosis)
- only renal disease
Crescent GN

98. Goodpastures´ syndrome
 It is charecterised antibodies against basal membrane of glomeruli
(alveolocapillary membrane)
 Etiology: combination of exogenous factors (smoking, infection, toxines)
with genetic predisposition (HLA B7, DR2)
 Pathogenesis: GBM is composed by collagen IV with proteins
(laminine, entaktine, tenascine) and proteoglycans
Goodpastures antigen
(localised in C-terminal non-collagen globular
domain (NC1) of the molecule 3 chain of collagen IV

formation of Ab (IgG1 – can activate complement)

damage of BM
 Clinical manifestation: typically presents with crescentic glomerulonephritis
+ pulmonary hemorrhage

99. Slowly progressive glomerulonephritis
 Group of GN called membrane-proliferative GN
 2 forms:
in 1 form : -  levels of complements in plasma
- subendothelial and mesangial deposits are present
findings: proteinuria or picture of nephrotic syndrom
in 2 form: - activation of complement is due to nephritic factor C3
- intramembranous deposits are present
findings: proteinuria or picture of nephritic syndrom (similary as in
RPGN)

100. Pathogenesis of nephrotic diseases

101. „Minimal changes“ GN (lipoid nephrosis)
 Especially in children
 Pathogenesis ambiguous – connection with
viral infections, vaccination, atopy,
application some drugs (antiphlogistics etc.),
Association with several HLA antigens (DRw7,
B8, B12 …)
 Finding: loss of negative charge
( permeability for some proteins –
albumins)
 Histologic pattern: fusion („loss“) of foot
processes of podocytes (pedicules), edematous
podocytes, some mesangial proliferation
 Therapy: corticoids

103. Focal (segmental) glomerulosclerosis
 More serious degree
- focal: < 50% glomeruli are affected
- diffuse: > 50% glomerulů are affected
- segmental: only a part of the glomerular tuft is
involved
- glomerulosclerosis: obliteration of capillary
lumens

104. Membranous GN
• Diffuse thickness of GBM due to deposition
of IK in basement membrane
• Strong association with HLA (B8, DR3) and
genes of alternative way of activation of
complements (Bf)
• Often secondary etiology:
- drugs (Au, penicilamin…)
- tumors (especially ca GIT)
- infection (hepatitis B)
• Clinical manifestation: nephrotic syndrome
with mikroscopic hematuria and sometimes
hypertension
• Therapy: according etiology

105. Stages of membranous GN

106. Idiopatic membranous glomerulopathy

107. Membranoproliferative (mesangiocapillary)
glomerulopathy
- Is characterised by hypercellularity of the glomerular cells and basement
membrane thickening
- 2 forms: classical form – proliferation of mesangial matrix with expansion to
capillary walls between endothelium and BM
disease of dension deposits – non-linear accumulation of material in
lamina densa of the basal membrane
- etiopathogenesis: ??? - association with infection (endocarditis, abscessus….)
- genetic faktors (HLA B8, DR3…)
- Clinical syndrome: nephrotic proteinuria with microhematuria, hypertension,
anemia and decreased levels of the complements (C3)

108. IgA nephropathy (Berger´s disease)
• Mesangioproliferative GN with deposits of IgA, event. C3
• Etiology: - unknown, clinical manifestation is associated with infection –
with latent period 2-3 days
- association with HLA (DQ, DP)
T-lymphocytes produce  levels of IL-2 (+  IR-2R) and they
are constantly stimulate

 production of IgA by B-lymphocytes
• Clinical manifestations: asymptomatic hematuria - nephrotic syndrome

109. Chronic glomerulonephritis
 Common terminal result of many glomerular
diseases
(„end stage kidney“)
 It is charecterised by different degrees of
sclerotization and proliferation
Pathogenesis: damage (loss) of nephrons

hyperperfusion

hyperfiltration

sclerosis of glomeruli

110. Glomerulopathy in connective tissue disorders
 SLE predominantly affects women, who account for 90% cases
 The age of onset is usually between 20 and 40 years
 Many different tissues and organs may be involved (the body produces
antibody against its own DNA), but renal involvement is the most
significant in terms of outcome
 Histologic pattern:
WHO classification – normal glomerules (typ I)
- mezangial GN (typ II)
- focal proliferative GN (typ III)
- diffuse proliferative GF (typ IV)
- membranous GN (typ V)
- glomerular sclerosis (typ VI)
Systemic lupus erythematosis

111. Vasculitis
 Heterogenous group of diseases characterised
by necrotizing inflammation of vessels
 Etiology: primary x secondary
 Pathogenesis:
- damage by immunocomplexes
- ANCA (pauciimmune form)
- damage by cells (IV. typ)

112. Henoch-Schönlein purpura
- systemic vasculitis affecting medium-sized vessels
 especially in children and younger people
 It is frequently develops post-infections
 Clinical manifestation: - non-trombocytopenic purpura
- affect joints, serose membrane, GIT and
glomeruli

alterations are similar to finding in IgA nephropathy

113. Polyarteritis nodosa
- is an inflammatory and necrotizing disease involving the
medium-sized and small arteries throughout the body.
- Men are more commonly affected than women
 Etiopathogenesis: usually unknown
 Clinical manifestation: variable – general symptoms +
specific symptoms
(skin, kidney, GIT, heart…)
 Histologic pattern: focal glomerular sclerosis, crescents

114. Pauci-immune necrotizing GN
Wegener´s granulomatosis
- is a vasculitis leading to sinus, pulmonary and renal disease
glomerulonephritis

90% of such patients have a positive ANCA
ANCA – react with neutrophils

respiratory burst of phagocytic cells

release of free radicals

degranulation

injury to endothelial cells

115. Diabetic nephropathy
= diabetic intracapillary glomerulosclerosis (sy Kimmelstielův-Wilsonův)
Etiopathogenesis: hyperglycemia affects conformation BM and mesangial matrix
 renal flow and glomerular pressure
(hyperfiltration)
 proliferation of cells
thickness GMB with expansion of mesangia
glomerulosclerosis
Clinical manifestation: latent stage - asymptomatic
incipient stage
manifest stage of diabetic nepropathy
chronic renal failure

116. Schematic demonstration of running diabetic
nephropathy

117. Amyloidosis
Kidney belong to organs most frequently affected by amyloidosis
AL amyloidosis – is a complication of myeloproliferative diseases (myelom,
(primary) makroglobulinémie)
AA amyloidosis – is a complication of chronic inflammatory diseases (RA,
(secondary) TBC, Crohn´s disease e.g.)
Clinical manifestation: nephrotic syndrom, subsequently renal failure
develops

118. Hereditary nephropaties
Alport syndrom
- Hereditar nephritis with deafness (X chromosome)
- Pathogenesis: congenital defect of collag synthesis

GMB very slight or with more layers
GN focal (diffuse) proliferation with segmental sclerosis
 hematuria, proteinuria or renal failure (males)
Congenital nephotic syndrom
- AR heredity
- Pathogenesis: defect of syntesis of basal membrane
- pronounced and non-selective proteinuria
 Nephrotic syndrom from first weeks of the life --- renal failure