Complete Renal Pathology

1. CLINICAL MANIFESTATIONS OF
RENAL DISEASES
1

2. Terms
• 1. Azotemia:
– elevation of blood urea nitrogen and creatinine levels
– related to a decreased glomerular filtration rate (GFR).
• Prerenal azotemia:
– Kidney hypoperfusion leading to decreased GFR in the
absence of parenchymal damage.
• Postrenal azotemia:
– Obstruction of urine flow below the level of kidney.
2

3. Terms
• 2. Uremia:
– azotemia with clinical manifestations and systemic
biochemical abnormalities
– failure of renal excretory function with metabolic
and endocrine alterations incident to renal damage
• gastrointestinal (e.g., uremic gastroenteritis),
• neuromuscular (e.g., peripheral neuropathy), and
• cardiovascular (e.g., uremic fibrinous pericarditis)
involvement.
3

4. Major syndromes
• 1. Acute nephritic syndrome, a glomerular
syndrome characterized by:
– acute onset of usually grossly visible hematuria
(RBCsin urine),
– mild to moderate proteinuria,
– azotemia,
– edema, and
– hypertension;
• Classic presentation of acute poststreptococcal
glomerulonephritis.
4

5. Major syndromes…
• 2. Nephrotic syndrome, a glomerular
syndrome , characterized by:
– heavy proteinuria (excretion of >3.5 gm of
protein/day in adults),
– hypoalbuminemia,
– severe edema,
– hyperlipidemia, and
– lipiduria (lipid in the urine).
5

6. Major syndromes
• 3. Asymptomatic hematuria or proteinuria, or a
combination of these two,
– manifestation of subtle or mild glomerular
abnormalities.
• 4. Rapidly progressive glomerulonephritis:
• Loss of renal function in a few days or weeks;
– microscopic hematuria,
– RBCs and RBC casts the urine sediment, and
– mild-to-moderate proteinuria.
6

7. Major syndromes
• 5. Acute renal failure:
– oliguria or anuria(Abnormally small production of
urine)
– with recent onset of azotemia.
• Causes:
– crescentic glomerulonephritis
– interstitial injury,
– vascular injury (such as thrombotic
microangiopathy), or
– acute tubular necrosis. 7

8. Major syndromes
• 6. Chronic renal failure characterized by :
– prolonged symptoms and signs of uremia
– end result of all chronic renal diseases.
• 7. Urinary tract infection characterized by:
– Bacteriuria and pyuria(white blood cells in the urine)
– Infection; symptomatic or asymptomatic, and it may
affect the kidney (pyelonephritis) or the bladder
(cystitis) only.
• 8. Nephrolithiasis (renal stones)
– renal colic, hematuria, and recurrent stone
formation. 8

9. Acute nephritic syndromes
Classically present with the following:
• Hypertension
• Hematuria
• Red blood cell casts
• Mild to moderate proteinuria
• Extensive inflammatory damage to glomeruli:
• fall in GFR
• uremic symptoms with salt and water retention,
• leading to edema and hypertension
9

10. Causes of Acute Nepritic
syndromes
• Poststreptococcal Glomerulonephritis
• Subacute Bacterial Endocarditis
• Lupus Nephritis
• IgA Nephropathy
• ANCA Small Vessel Vasculitis
• Membranoproliferative Glomerulonephritis
• Mesangioproliferative Glomerulonephritis
10

11. Poststreptococcal Glomerulonephritis
• Immune-mediated disease involving:
– Streptococcal antigens
– Circulating immune complexes
– Activation of complement in association with
cell-mediated injury.
11

12. Nephrotic Syndrome
• Clinical complex that includes the following:
– (1) massive proteinuria: 3.5 gm or more in 24 hrs in
adults;
– (2) hypoalbuminemia; with plasma albumin levels
less than 3 gm/dL;
– (3) generalized edema
– (4) hyperlipidemia and lipiduria.
• At the onset there is little or no azotemia,
hematuria, or hypertension. 12

13. Pathogenesis
• Initial event is a derangement in the capillary
walls of the glomeruli,
• Increased permeability to plasma proteins
– Heavy proteinuria -decreased serum albumin i.e.
hypoalbuminemia.
– Drop in plasma colloid osmotic pressure : generalized
edema
– Decreased plasma volume- decreased GFR
– Compensatory secretion of aldosterone; retention of
salt & water by kidneys;
– Further aggravates edema: ANASARCA 13

14. Pathogenesis
• Genesis of the hyperlipidemia is more obscure:
– hypoalbuminemia triggers increased synthesis of
lipoproteins in the liver.
– abnormal transport of circulating lipid particles and
impairment of peripheral breakdown of
lipoproteins.
• Lipiduria; increased permeability of the GBM to
lipoproteins.
14

15. Causes of Nephrotic syndrome
Primary Glomerular Disease
• Membranous GN
• Minimal-change disease
• Focal segmental glomerulosclerosis
• Membranoproliferative GN
• IgA nephropathy and others
% in
Children Adults
5 30
65 10
0 35
10 10
10 15
15

16. Causes of Nephrotic syndrome
• Systemic Diseases with Renal Manifestations
– Diabetes mellitus‡
– Amyloidosis‡
– Systemic lupus erythematosus
– Ingestion of drugs (gold, penicillamine, "street
heroin")
– Infections (malaria, syphilis, hepatitis B, HIV)
– Malignancy (carcinoma, melanoma)
– Miscellaneous (bee-sting allergy, hereditary
nephritis)
16

17. 17

18. Pathogenesis of Glomerular
diseases
18

19. Normal Physiology of Glomerular
filtration
• Extraordinarily high permeability to water
and small solutes and
• Almost complete impermeability to
molecules of the size and charge of albumin
(size: 3.6 nm radius)
19

20. Normal Physiology of Glomerular
filtration
• Selective permeability, called glomerular
barrier function
– larger, the less permeable
– more cationic, the more permeable
20

21. Normal Physiology of Glomerular
filtration
• Nephrin, a transmembrane glycoprotein-major
component of the slit diaphragms between foot
processes.
• Nephrin and its associated proteins podocin, have a
crucial role in maintaining the selective permeability
• Increased permeability:
– Aqcquired defects in the function or structure of slit
diaphragms;
– Important mechanism of proteinuria (hallmark of the
nephrotic syndrome)
21

22. Physiologic role of Glomerular components and consequences
in Glomerular injury
Component Physiologic function Consequence of
injury
Related glomerular
disease
Endothelial cells •Glomerular
perfusion
•Prevent leukocyte
adhesion
•Prevent platelet
aggregation
•Vasoconstriction
•Leukocyte
infiltration
•Microthrombi
•ARF
•Proliferative GN
•Thrombotic
microangiopathies
Mesangial cells Control GFR Proliferation and
increased matrix
Membranoproliferative
GN
Visceral Epithelial
cells
Prevent plasma
protein filtration
Proteinuria MCD
GBM Prevent plasma
protein filtration
Proteinuria Membarnous GN
Parietal Epithelial cell Maintain Bowman’s
space
Crescent
formation
Membranous, RPGN
22

23. Glomerular Diseases
• Glomeruli may be injured by diverse mechanisms:
• Primary Glomerular Diseases:
– Kidney is the only or predominant organ involved
• Secondary Glomerular Diseases:
– Immunologically mediated diseases e.g. SLE)
– Vascular disorders e.g. hypertension
– Metabolic diseases such as diabetes mellitus,
– Some hereditary conditions such as Alport syndrome
23

24. Pathogenesis of Glomerular Injury
• 1. Most of the Primary and secondary injuries
have immunologic pathogenesis
– Primarily Antibody-mediated (Immune Complex
reactions)
– Cell-mediated immune reaction ; in some cases
• 2. Non-immune mechanism
24

25. Pathogenesis of Glomerular Injury
• I. Immunologic mechanism:
• A. Antibody-mediated glomerular injury
– Immune complex disease: In situ & circulating
– Anti-neutrophil cytoplasmic antibodies (ANCA)
– Anti-endothelial cell antibodies (AECA)
• B. Cell mediated glomerular injury
25

26. Immunologic Mechanism of
Glomerular injury
A. Antibody-mediated: Immune complex (IC);
Complex of IgG, IgM IgA and complement:
• 1. IC In situ:
– Fixed: Anti-Glomerular Basement Membrane (GBM)
Antibody Glomerulonephritis
• antibodies are directed against fixed antigens in the
GBM
– Planted antigens: DNA, bacterial products: protein of
group A streptococci; large aggregated proteins (e.g.,
aggregated IgG),
26

27. Immunologic Mechanism of Glomerular
injury
• 2. Nephritis Caused by Circulating Immune
Complexes; Antigen not of glomerular origin:
– Endogenous;
• SLE GN,
–Exogenous;
• bacterial (streptococcal),
• viral (hepatitis B),
• parasitic (Plasmodium falciparum
malaria),
• Spirochetal (Treponema pallidum)
27

28. Pathogenesis of Glomerular injury in IC-
mediated reaction
• Immune Complexes:
• Formed in situ or in the circulation
• Trapped in the glomeruli
– Activation of complement and the recruitment of
leukocytes.
– Inflammation
• Glomerular lesions;
• leukocytic infiltration into glomeruli and
• proliferation of endothelial, mesangial, and parietal
epithelial cells.
28

29. Pathogenesis of Glomerular injury in
IC- mediated reaction
• Electron microscopy reveals the immune
complexes deposits that lie at one of three
sites:
– in the mesangium,
– between the endothelial cells and the GBM
(subendothelial deposits),
– or between the outer surface of the GBM and the
podocytes (subepithelial deposits).
29

30. 30

31. Other mechanisms of Antibody
mediated injury
• Anti-neutrophil cytoplasmic antibodies (ANCA)-
associated vasculitis is the most common cause
of RPGN
• Massive necrosis of the vascular wall with endo-
and peri-vascular inflammatory infiltrates
• ANCAs activate neutrophils and monocytes to
produce endothelial injury thru generation of
free radicals
31

32. Other mechanisms of Antibody
mediated injury
• Anti-endothelial cell antibodies (AECA)
• Autoantibodies agaist endothelial Ag in:
– Inflammatory vasculitis
– Glomerulonephritis
• Abs increase adhesiveness of leukocytes to
endothelial wall
32

33. Cell-Mediated Immune
Glomerulonephritis
• Injury by sensitized T cells, formed during the
course of a cell-mediated immune reaction
• T cell-mediated injury
• no deposits of antibodies or immune complexes or
• deposits do not correlate with the severity of
damage.
• Even when antibodies are present, T-cell-
mediated injury cannot be excluded.
33

34. Mediators of immunologic injury
• Activation of complement;
• Generation of chemotactic agents (mainly C5a)
and recruitment of neutrophils and monocytes.
– Neutrophils;
• release proteases, which cause GBM degradation;
• oxygen-derived free radicals, which cause cell
damage;
• arachidonic acid metabolites, which contribute to
reduction in GFR.
34

35. Mediators of immunologic injury
• Complement-dependent but not neutrophil-dependent injury,
due to an effect of the C5-C9 component (MAC)
– causes epithelial cell detachment
– stimulates mesangial and epithelial cells to secrete
various mediators of cell injury.
• MAC also:
• up-regulates TGF-β receptors on podocytes;
• TGF-β stimulates synthesis of extracellular matrix- alters GBM
composition and thickening.
35

36. Other mediators of Cell injury
– Monocytes and macrophages, when activated,
release a vast number of biologically active
molecules;
– Platelets, which aggregate in the glomerulus
during immune-mediated injury and release
prostaglandins and growth factors;
36

37. Other mediators of Cell injury
• Glomerular cells (epithelial, mesangial, and
endothelial):
– secrete mediators; interleukin, arachidonic acid
metabolites, growth factors
• Fibrin-related products;
• leukocyte infiltration
• glomerular cell proliferation
• intraglomerular thrombosis.
37

38. Mediators of immunologic injury
38

39. Non-immune mechanism of
glomerular injury
• Metabolic: DM- due to hyperglycemia
• Hemodynamic: HTN, intraglomerular HTN in
FSGS
• Deposition disease: Amyloidosis
• Infectious diseases: HBV, HCV, HIV, E Coli
• Drugs: MCD; NSAIDS
• Inherited: Alport’s disease; Can’t see, can’t hear
& can’t pee
39

40. Classification
• Primary Glomerular Diseases
– Minimal-change disease
– Focal and segmental glomerulosclerosis
– Membranous nephropathy
– Acute postinfectious
– Membranoproliferative
– IgA nephropathy
– Chronic GN
40

41. Classification
• Glomerulopathies Secondary to Systemic
Diseases
– Lupus nephritis (systemic lupus erythematosus)
– Diabetic nephropathy
– Amyloidosis
– GN secondary to lymphoplasmacytic disorders
– Goodpasture syndrome
– Microscopic polyangiitis
– Wegener's granulomatosis
– Henoch-Schönlein purpura
– Bacterial endocarditis-related GN 41

42. 42

43. Acute Glomerulonephritis:
Pathogenesis and Morphology
43

44. Normal Anatomy of Kidney
44

45. 45

46. Normal Glomerulus
•
46

47. Normal glomerulus
• Glomerulus has been cut through the
vascular pole which is seen at 6 o’clock.
47

48. • Glomerular filtration membrane/barrier
48

49. 49

50. Acute Proliferative (Poststreptococcal,
Postinfectious) Glomerulonephritis
• Infections are associated with overcrowding
and poor hygiene.
• Age group:
– 6 to 10 yrs, but adults may also get affected.
50

51. Pathogenesis of APGN
APGN is an immune complex mediated disease
(type 3 hypersensitivity rxn):
1). Exposure to antigen:
APGN appears 1 to 4 wks after infection by group
A β-hemolytic streptococci (90% cases= 12,4,1
serotypes) of the pharynx or skin (impetigo).
2). Immune complexes (antibody+antigen)
formed in blood are carried to kidneys and
deposited in glomerular capillary wall.
51

52. Pathogenesis of APGN continued
3). Classical pathway of complement system is
activated:
- Complement products C3a and C5a attract neutrophils and
monocytes to the glomeruli.
- Injury of glomeruli by inflammatory mediators.
52

53. • Nonstreptococcal postinfectious glomerulonephritis:
- A similar form of GN occurs d/t other infections:-
:bacterial- staphylococcal endocarditis, pneumococcal
pneumonia, and meningococcemia
:viral- hepatitis B and C, mumps, HIV, varicella, and
:parasitic- malaria, toxoplasmosis
53

54. Membranous Glomerulopathy
• An immune complex mediated disease.
• 85 % of cases= Primary membranous glomerulopathy
(idiopathic MG); it is an autoimmune disease.
• 15 % cases: associated with other causes=
Secondary membranous glomerulopathy:
- Drugs: NSAIDs, Gold, Penicillamine,
- Underlying malignant tumors: Ca of lung and colon,
and melanoma.
- SLE, Hepatitis B and C.
54

55. Pathogenesis of Primary MG
1). Formation of autoantibodies to an antigen
in the visceral epithelial cells.
2). Immune complex (antibody+antigen) forms
in-situ.
3). Activation of classical complement pathway
by the ICs.
55

56. 4). Membrane attack complex (C5b-C9):
activates glomerular epithelial and mesangial
cells.
Mesangial cells produce proteases and ROS, which
cause capillary wall injury and proteinuria.
• Inflammatory cells are scant in the glomeruli.
56

57. Pathogenesis of Secondary Membranous
Glomerulopathy continued
 In SLE, pathogenesis is type 3 hypersensitivity
reaction:
 Autoantibodies+ self antigen= immune complex.
 ICs are deposited in the glomerular capillary wall:
 Classical pathway of complement system is
activated.
57

58. Pathogenesis of Secondary Membranous Glomerulopathy
continued
 Hepatitis B and C infection:
- Immune complexes (antibodiy+ antigen) are
deposited in the glomerular wall which activate CP
of complement system.
58

59. Membranoproliferative Glomerulonephritis
(MPGN)
Synonym: mesangiocapillary
glomerulonephritis
It can be primary or secondary.
Primary MPGN: two types
- Type 1 and Type 2
59

60. Pathogenesis of type 1 MPGN
1. Presumed antigens: hepatitis B and C virus.
2. Immune complexes (antibodies+ antigens) are
deposited in the glomerular capillay wall= Type
3 hypersensitivity rxn.
3. Activation of CP of complement system and
inflammation.
60

61. Pathogenesis of type 2 MPGN
1. Type 2 MPGN= dense deposit disease.
2. Activation of alternative pathway of
complement system. Inciting antigen: unknown.
3. Patients have an autoantibody (C3 nephritic
factor) which binds with C3 convertase and
stabilizes it; that means it can not be degraded.
 As a result there is persistent activation of C3 by C3
convertase.
61

62. Secondary MPGN
• It is invariably type I and pathogenesis is
similar to type I.
• Arises in the following settings:
chronic infections: HIV, hepatitis B and C infection,
chronic visceral abscesses.
Autoimmune disease: SLE
Malignant diseases: CLL and lymphoma
62

63. Minimal-Change Disease (MCD)
• Synonym: lipoid nephrosis
• More common in children (2 to 6 yrs).
• Sometimes follows a respiratory infection or
immunization.
63

64. Pathogenesis of MCD
• Exact mechanism is not clearly
known.
• Two hypotheses are as follows:
a). Loss of charge-dependent GFBF:
 Some kind of immune dysfunction produces
loss of glomerular polyanions causing deranged
charge-dependent barrier function of GFM.
64

65. Pathogenesis of MCD continued
b). Mutations in structural proteins, which are
localized in the filtration slits lead to loss of
size-dependent barrier function of GFM.
65

66. Focal Segmental Glomerulosclerosis (FSGS)
• FSGS occurs in the following settings:
As a primary disease (Idiopathic FSGS): no associated
systemic diseases.
Secondary to other diseases (Secondary FSGS): HIV
infection, sickle-cell disease, and massive obesity.
As an adaptive response to loss of renal tissue in other
renal disorders (hypertensive nephropathy, unilateral
renal agenesis).
 Mutations in genes that encode proteins of filtration
slits.
66

67. • Pathogenesis is similar to that of MCD.
67

68. Rapidly progressive GN (Crescentic GN)
 Does not denote a specific disease process.
 Is a syndrome associated with severe
glomerular injury b/o other glomerular
diseases.
 Rapid and progressive loss of renal function
and death from RF can occur within weeks to
months.
68

69. Classification of Causes of RPGN
A). Type 1: cause is anti-GBM antibody
- Renal limited and
- Good Pasture Syndrome
B). Type 2: caused by deposition of ICs in the
glomeruli:
 APGN
 Lupus nephritis
 Henoch-Schönlein purpura
IgA nephropathy
69

70. C). Type 3:
- Wegener granulomatosis
- Microscopic polyangiitis
In 50% cases, the disorder is idiopathic: cause is
not known.
70

71. HIV Nephropathy
• HIV infection can cause:
- Postinfectious glomerulonephritis
- Secondary MPGN
- FSGS
71

72. Ig A Nephropathy
• Synonym: Berger disease.
• It was first described by Berger and Hinglais in 1968.
• Most common type of glomerulonephritis worldwide.
• Ig A:
– two subclasses: Ig A1 and Ig A2
• Only Ig A1 can cause nephropathy.
72

73. Pathogenesis of Ig A Nephropathy
a). Immune complex containing Ig A1 is
deposited in the mesangium of glomerulus by
unknown mechanism.
b). Immune complexes activate mesangial cells
which proliferate and produce mesangial
matrix, growth factors and cytokines.
Cytokines recruit inflammatory cells.
c). ICs also activate alternative pathway of
complement system.
73

74. Henoch-Schönlein Purpura
• It is an acute IgA–mediated disorder.
• generalized vasculitis involving the small vessels
of the skin, the GI tract, the kidneys, the joints,
and, rarely, the lungs and the CNS.
• most common in children 3 to 8 years old, but it
also occurs in adults, in whom the renal
manifestations are usually more severe.
• onset often follows an URTI.
74

75. • Pathogenesis same as in IgA nephropathy.
• IgA nephropathy and Henoch-Schönlein
purpura are thought to be manifestations of
the same disease.
75

76. Pathogenesis of Glomerulonephritis in a nutshell
S.N. Type of
Glomerulonephritis
Pathogenesis
1. APGN Type 3 hypersensitivity reaction (IC mediated)
Activation of classical complement pathway
C3a, C5a recruit inflam cells, Glomerular injury by
inflammatory mediators.
2. Primary Membranous
Glomerulopathy Activation of classical complement pathway
C5b-C9 Glomerular epith. cells and mesangial cells
activated, produce proteases and oxygen species gl injury
3. Secondary Membranous
Glomerulopathy
Eg. SLE: Type 3 hypersensitivity reaction and Classical Pathway
of complement activation
4. Type 1 Primary MPGN As in APGN.
76

77. Pathogenesis of Glomerulonephritis in a nutshell
S.N. Type of
Glomerulonephritis
Pathogenesis
5. Type 2 Primary MPGN - Activation of alternative complement pathway
- C3 nephritic factor binds with C3 convertase and persistent
activation of C3 by C3 convertase occurs.
6. Secondary MPGN Same as in type 1 Primary MPGN
7. Minimal-change disease a. Loss of charge-dependent barrier function of glomerulus
b. Loss of size-dependent barrier function of glomerulus
8. FSGS Same as in Minimal-change disease
9. Ig A Nephropathy - Deposition of immune complex containing Ig A1 in the
mesangium which induce proliferation of mesangial cells and
secretion of growth factor and cytokines. Mesangial
matrix expansion and inflammation occur.
- Alternative pathway of complement system also activated.
77

78. Morphological features of Glomerulonephritis
Acute postinfectious Glomerulonephritis:
 enlarged, diffusely hypercellular glomeruli.
Hypercellularity is caused by:
1. infiltration by leukocytes: neutrophils and
monocytes;
2. proliferation of endothelial and mesangial cells;
and
In severe cases crescent formation occurs.
78

79. Morphology of APGN continued
• swelling of endothelial
cells.
• combination of
proliferation, swelling,
and leukocyte
infiltration obliterates
the capillary lumens.
79

80. • Normal glomerulus • APGN
80

81. Morphological features in APGN contd.
• Products of:
type 3 hypersensitivity reaction and
complement activation are found within the
glomerulus which can be seen only by
immunofluorescence or electron microscopy.
81

82. Immunofluorescence microscopic
features in APGN continued
Deposits of Ig G, Ig M and C3 are found in:
Subepithelial location in the form of humps. These
are characteristic feature of APGN.
Deposits are also found in
- glomerular basement membrane,
- subendothelial location and
- mesangium as well.
82

83. Subepithelial humps
83

84. Immunofluorescence microscopic picture
of APGN
Deposits are seen as
bright green fluorescence
in a granular, bumpy
pattern.
84

85. Electron microscopic picture of APGN
Subepithelial location
of deposits, often
having the appearance
of “humps”
85

86. Morphology of MGN
• Uniform, diffuse filtration
membrane thickening,
but cellularity is not
increased.
• Capillary wall thickening
is due to:
a). Subepithelial deposits of
immune complexes:
between BM and visceral
epithelium
86

87. b). and diffusely thickened
glomerular basement
membrane: subepithelial
immune deposits stimulate
glomerular epithelial cells
to secrete basement
membrane material.
87

88. Electron microscopic features of MGN
GBM spikes are present:
The spikes represent
intervening matrix of
basement membrane
between the subepithelial
deposits.
88

89. • Foot processes of podocytes are effaced in
MGN.
89

90. Immunofluorescence microscopic features in
membranous glomerulopathy
Deposits of IgG and
complement
appear in a diffuse
granular pattern by
immunofluorescence.
90

91. Minimal-change disease
• Glomeruli are normal by light microscopy.
91

92. EM features in MCD
• The only lesion is diffuse effacement of foot
processes of visceral epithelial cells.
92

93. Morphology of MCD
• Effacement of foot processes is d/t flattening,
retraction and swelling of the processes.
– It is also seen in membranous glomerulopathy,
FSGS and diabetic nephropathy.
• It is only when effacement is associated with
normal glomeruli by light microscopy that the
diagnosis of MCD can be made.
93

94. Morphology in MPGN
A]. Light microscopic features:
• By light microscopy, both types of MPGN are
similar.
1. Glomeruli are large and hypercellular.
• Hypercellularity is produced by:
- Proliferation of mesangial cells and endothelial
cells
- Infiltration of glomerulus by leukocytes.
2. Expansion of mesangial matrix.
94

95. Morphology in MPGN continued
3. Lobular accentuation:
 Glomeruli have an accentuated “lobular”
appearance due to proliferating mesangial cells and
increased mesangial matrix.
95

96. Morphology in MPGN continued
4. Crescents are present in
many cases.
• These are made up of
proliferating cells.
96

97. Morphologic features specific to Type 1 MPGN
5. GBM is thickened in type I MPGN.
• Glomerular capillary wall often shows a “double-
contour” or “tram-track” appearance, especially
evident in silver or PAS stains.
• Tram-tracking is caused by “duplication” of the
basement membrane (also commonly referred to
as splitting), b/o new basement membrane
synthesis in response to subendothelial deposits
of immune complexes.
97

98. Morphology in MPGN continued
• Silver-stained section shows tram-tracking.
98

99. Interposition of mesangial cytoplasm occurs into the
split glomerular basement membrane.
99

100. • Tram in Oslo • Tram track in Belgium
100

101. EM features in MPGN
• Type 1 and type 2 MPGN differ in their
ultrastructural features.
A]. Type 1 MPGN:
- Presence of discrete subendothelial electron-
dense deposits.
- Mesangial and occasional subepithelial deposits
may also be present.
101

102. 102

103. Subendothelial electron-dense deposits in type 1 MPGN
103

104. B]. Type 2 MPGN (Dense
Deposit Disease):
- ribbon-like electron-
dense structure due to
the deposition of dense
material of unknown
composition in the
GBM.
104

105. Immunofluorescence microscopy in MPGN
• Type 1 MPGN:
– Classical Pathway Complement components C3, C1
and C4 and Ig G are deposited in a granular pattern.
• Type 2 MPGN:
- Alternative complement pathway component C3
present in linear or granular pattern but classical
pathway complement components (C1, C4) and Ig G
absent.
- C3 is also present in the mesangium in characteristic
circular aggregates (mesangial rings).
105

106. • Mesangial rings
106

107. Light microscopic features in FSGS
In this disease:
There is sclerosis
of some, but not all
glomeruli (thus, it is focal)
and in the affected
glomeruli, only a portion
of the capillary tuft is
involved (thus, it is segmental).
107

108. • In the focus of sclerosis, there is:
- collapse of capillary loops,
- increase in mesangial matrix, and
- deposition of plasma proteins along the capillary wall
(hyalinosis)
- presence of lipid droplets and foam cells
108

109. • EM features in FSGS:
• In both sclerotic and nonsclerotic areas:
- There is diffuse effacement of foot processes of
podocytes.
• IF microscopic features in FSGS:
– IgM and C3 may be present in the sclerotic areas
and/or in the mesangium.
109

110. Morphology of glomerulus in IgA nephropathy
• IgA is deposited mainly
within the mesangium,
which then increases
mesangial cellularity as
shown at the arrow.
110

111. IF microscopic features
• Immunofluorescence
pattern demonstrates
positivity with antibody
to IgA.
111

112. Electron microscopic features of Ig A
Nephropathy
• Electron-dense deposits in the mesangium
112

113. Light microscopic features of glomerular diseases in a
nutshell
S.N. Type of GN Light microscopic changes in the glomerulus
1. APGN • Enlarged, diffusely hypercellular glomeruli
(inflammatory cells, mesangial cells and endothelial
cells)
• Obliteration of capillary lumen
2. MGN  Diffuse filtration membrane thickening
3. MCD  Glomeruli appear normal by light microscopy.
4. MPGN  Glomeruli are large and hypercellular ( inflammatory cells,
mesangial cells and endothelial cells).
 Increased mesangial matrix
 Lobular accentuation
113

114. Light microscopic features of glomerular diseases in a nutshell
continued
S.N. Type of Glomerulonephritis Light microscopic changes in the glomerulus
5. FSGS  Focal and segmental sclerosis of glomeruli
6. Ig A nephropathy  Expansion of mesangial matrix
 Proliferation of endothelial and mesangial cells
114

115. Electron microscopic features of glomerulonephritis in a
nutshell
S.N. Type of Glomerulonephritis Electron microscopic features
1. APGN  Subepithelial deposition of immune complex in the form
of humps
2. MGN  Discrete subepithelial deposition of immune complex
 GBM spikes
 Effacement of foot processes of podocytes
3. MCD o Effacement of foot processes of podocytes
3. Type 1 MPGN  Discrete subendothelial electron-dense deposits
 Tram-track appearance of GBM
4. Type 2 MPGN • Ribbon like electron-dense deposit in the GBM
115

116. Electron microscopic features of glomerulonephritis in a
nutshell continued
S.N. Type of GN Electron microscopic features
5. Ig A
nephropathy
Electron-dense deposits in the mesangium
6. FSGS Effacement of foot processes of podocytes
116

117. Immunofluorescence microscopic features of
glomerulonephritis in a nutshell
S.N. Type of GN Immunofluorescence microscopic features
1. APGN Deposits are seen as bright green fluorescence in a granular, bumpy
pattern. C1, C4, C3 (classic pathway complement system products)
and Ig G present.
2. Primary MGN Deposits of IgG and complement C5b-C9 appear in a diffuse granular
pattern
3. Secondary MGN Deposits contain same components as in APGN
4. Type 1 MPGN Deposits contain same components as in APGN.
5. Type 2 MPGN C3 present in linear or granular pattern but classical pathway
components and Ig G absent.
117

118. Immunofluorescence microscopic features of
glomerulonephritis in a nutshell continued
S.N. Type of GN Immunofluorescence microscopic features
6. Ig A Nephropathy Immune complex deposit containing Ig A1 and C3 in the
mesangium. Classical pathway components not present.
7. FSGS IgM and C3 may be present in the sclerotic areas and/or in
the mesangium. Classical pathway components not
present.
118

119. Type 3 hypersensitivity
reaction
1. APGN
2. Secondary MGN
3. Type 1 MPGN
4. Secondary MPGN
Activation of alternative
complement pathway
1. Type 2 MPGN
2. Ig A nephropathy
119

120. Effacement of foot processes of podocytes
1. Minimal-change disease
2. Focal segmental glomerulosclerosis
3. Membranous glomerulopathy
4. Diabetic nephropathy
120

121. Subepithelial deposits
1. Acute Proliferative
Glomerulonephritis
2. Membranous
glomerulopathy
1. Type 1 MPGN
Subendothelial deposits
Deposit in the GBM
1. Type 2 MPGN
121

122. Morphology in RPGN
• kidneys are enlarged and pale, often with
petechial hemorrhages on the cortical
surfaces.
• Crescents are formed by proliferation of
parietal cells and by migration of monocytes
and macrophages into the urinary space.
Neutrophils and lymphocytes may be present.
– Fibrin strands are frequently prominent between
the cellular layers in the crescents.
122

123. Crescents
123

124. Morphology in RPGN contd.
• Crescents eventually obliterate Bowman space
and compress the glomerular tuft.
• Electron microscopy may show distinct ruptures
in the GBM, the severe injury that allows
leukocytes, proteins, and inflammatory mediators
to reach the urinary space, where they trigger the
crescent formation.
• In time, most crescents undergo sclerosis.
124

125. • Anti-GBM antibody-mediated disease is
characterized by linear deposits of IgG and, in
many cases, C3 in the GBM.
• In some of these patients, the anti-GBM
antibodies cross-react with pulmonary alveolar
basement membranes to produce the clinical
picture of pulmonary hemorrhage associated
with renal failure (Goodpasture syndrome).
125

126. Nephrotic syndrome
• Nephrotic syndrome is characterized by:
a). Heavy proteinuria (>3.5 gm/1.73 sq m/24 hours
b). Hypoalbuminemia (< 3.0 gm/dL)
c). Hyperlipidemia and lipiduria
e). Generalized edema
Severe generalized edema is called anasarca.
There is often an associated hypercoaguable
state.
126

127. Left sample: urine with lipid
Right sample: normal urine
127

128. • Patients presenting with proteinuria without
the other components of nephrotic syndrome
are described as having nephrotic-range
proteinuria.
128

129. Pathophysiology of Nephrotic syndrome
1). Hypoalbuminaemia
2). Compensatory increase in protein synthesis by
the liver including lipoproteins LDL and VLDL =
Hyperlipidemia
3). Hyperlipidemia leads to loss of lipid in urine =
lipiduria.
4). Hypercoagulability seen in nephrotic syndrome
results from the loss of anticoagulants (which are
proteins) in the urine and increased synthesis of
procoagulatory factors by the liver. 129

130. 5). Edema is d/t a decrease in oncotic pressure
from hypoalbuminaemia, as well as a primary
defect in sodium excretion.
6). Patients with nephrotic syndrome are also at
increased risk of infection due to loss of
immunoglobulins and complement and other
compounds being lost in the urine.
130

131. Etiology of Nephrotic Syndrome
1. Membranous
glomerulonephropathy:
most common cause in
adults.
2. Minimal-change
disease: most common
cause in children.
131

132. Etiology of Nephrotic Syndrome continued
Other causes:
3). FSGS
4). MPGN
5). Ig A Nephropathy
132

133. Etiology of Nephrotic Syndrome continued
Systemic diseases which cause Nephrotic
syndrome:
1. Diabetic nephropathy
2. Lupus nephritis
133

134. • Memory clue:
- Disease which cause effacement of foot
processes of podocytes cause nephrotic
syndrome: MCD, MGN, Diabetic nephropathy
and FSGS.
134

135. Nephritic Syndrome
• Nephritic syndrome is characterized by:
– Hematuria with red blood cell (RBC) casts present
in the urine
– Proteinuria: <3.5 g/day
– Hypertension
– Uremia
– azotemia (elevated blood urea nitrogen)
– oliguria (low urine output <400 mL/day)
135

136. • Azotemia: elevation of blood urea nitrogen
(BUN) (reference range, 8-20 mg/dL) and/or
serum creatinine (normal value, 0.7-1.4
mg/dL) levels.
• Uremia: in the presence of azotemia, when
clinical manifestations develop then it is called
uremia. Eg. uremic pericarditis.
136

137. Etiology of Nephritic syndrome
1. APGN
2. RPGN
3. Ig A nephropathy
4. Lupus nephritis
137

138. • After treatment • Before treatment:
moon-face in nephrotic
syndrome
138

139. 139

140. 140

141. 141

142. • Thank You !!
142

143. Glomerular filtration membrane:
- Is highly permeable to water.
- Permeability of solute is size and charge-dependent:
larger, the less permeable and the more cationic, the more
permeable.
- So, the membrane prevents the passage of large
and/or negatively charged molecules (anionic
molecules), such as albumin. This barrier is called
glomerular filtration barrier.
143

144. Factors responsible for glomerular filtration
barrier
1). Negatively charged molecules(proteoglycans of GBM and
sialoglycoproteins of epithelial and endothelial cell
membrane)are responsible for charge-dependent glomerular
filtration barrier function of glomerular filtration membrane.
2). Filtration slits and the proteins in the slits are responsible for
size-dependent as well as charge-dependent glomerular
filtration barrier function.
144

145. • Entire glomerular tuft is
supported by mesangial
cells and mesangial
matrix lying between
the capillaries.
145

146. • Mesangial cells:
- are contractile and phagocytic
- are capable of proliferation,
- can lay down both matrix and collagen
- can secrete several biologically active mediators.
Normal mesangium contains about 2 to 4
mesangial cells.
146

147. • About 15% of
glomerular filtration
occurs through the
mesangium, with the
remainder through the
fenestrated
endothelium.
147

148. Composition of Urine
• water 95%
• urea
• chloride
• sodium
• potassium
• creatinine
148

149. • Protein and glucose are not present in urine
because of glomerular filtration barrier.
149

150. Normal glomerulus
• Glomerular capillary loops thin and delicate.
• Endothelial and mesangial cells normal in number
• Surrounding tubules normal
150

151. Normal glomerulus stained with PAS stain
• Basement membranes of glomerular capillary loops and tubular
epithelium highlighted.
• Capillary loops of this normal glomerulus are well-defined and thin.
• Endothelial cells are seen in capillary loops.
• Mesangial regions are of normal size.
• Podocytes along visceral epithelial surface. Bowman's space is seen along
with parietal epithelial cells.
151

152. 152

153. 153

154. 154

155. 155

156. Acute tubular necrosis
156

157. Defn:
• Acute tubular injury (ATI) is a
clinicopathologic entity characterized
clinically by acute renal failure and often, but
not invariably, morphologic evidence of
tubular injury, in the form of necrosis of
tubular epithelial cells.
157

158. • It is the most common cause of acute kidney
injury (acute renal failure).
• ATI can be caused by a variety of conditions.
158

159. 1)Ischemia, due to decreased or interrupted
blood flow, examples:
Diffuse involvement of the intrarenal blood
vessels such as in microscopic polyangiitis,
malignant hypertension, microangiopathies
and systemic conditions associated with
thrombosis (e.g., HUS, TTP and DIC or
decreased effective circulating blood volume,
as occurs in hypovolemic shock).
159

160. 2)Direct toxic injury to the tubules by
endogenous
e.g., myoglobin,hemoglobin, monoclonal light
chains, bile/bilirubin) or exogenous agents
(e.g., drugs, radiocontrast dyes, heavy
metals,organic solvents).
160

161. Causes
ATI is a reversible process that arises in a variety
of clinical settings.
severe trauma
acute pancreatitis,
 inadequateblood flow to the peripheral
organs, usually followed by marked
hypotension and shock.
This pattern is called ischemic ATI.
161

162. The second pattern, called nephrotoxic
ATI, is caused by a multitude of drugs,
 such as gentamicin;
 radiographic contrast agents; poisons, including
heavy
 metals (e.g., mercury); and organic solvents (e.g.,
carbontetrachloride).
 Combinations of ischemic and nephrotoxic ATI
also can occur.
162

163. • exemplified by mismatched blood transfusions
and other hemolytic crises causing
hemoglobinuria and skeletal muscle injuries
causing myoglobinuria.
• Such injuries result in characteristic
intratubular hemoglobinor myoglobin casts,
respectively; the toxic iron contentof these
globin molecules contributes to the ATI.
163

164. Pathogenesis
• The critical events in both ischemic and
nephrotoxic ATI are believed to be
(1) Tubular injury and
(2) Persistent and severe disturbances in blood
flow
164

165. 1) Tubule cell injury: Tubular epithelial cells are
particularly
• sensitive to ischemia and are also vulnerable to toxins.
• Several factors predispose the tubules to toxic injury,
• including an increased surface area for tubular
reabsorption,
• active transport systems for ions and
• Organic acids, a high rate of metabolism and oxygen
consumption,
165

166. • Ischemia causes numerous structural and functional
alterations in epithelial cells.
• One early reversible result of ischemia is loss of cell
polarity due to redistribution of membrane proteins
(e.g., the enzyme Na,K+-ATPase) from the basolateral to
the luminal surface of the tubular cells, resulting in
abnormal ion transport across the cells and increased
sodium delivery to distal tubules
166

167. • Ischemic tubular cells express cytokines and
adhesion molecules, thus recruiting
leukocytes that appear to participate in the
subsequent injury.
• Finally injured cells detach from the basement
membranes and cause luminal obstruction,
increased intratubular pressure, and
decreased GFR.
167

168. • Disturbances in blood flow: Ischemic renal injury
is also
• characterized by hemodynamic alterations that
cause reduced GFR. The major one is intrarenal
vasoconstriction, which results in both reduced
glomerular blood flow and reduced oxygen
delivery to the functionally important tubules in
the outer medulla (thick ascending limb and
straight segment of the proximal tubule).
168

169. 169

170. Morphology
• focal tubular epithelial necrosis at multiple points
along the nephron, with large skip areas in between,
often accompanied by rupture of basement
membranes (tubulorrhexis) and occlusion of tubular
lumensby casts. The distinct patterns oftubular injury
in ischemic and toxic ATI .
• Straight portion of the proximal tubule and the
ascending thick limb in the renal medulla are the
target sites.
• but focal lesionsmay also occur in the distal tubule,
often in conjunction with casts.
170

171. • Eosinophilic hyaline casts, as well as
pigmented granular casts, are common,
particularly in distal tubules and collecting
ducts. These casts consist principally of Tamm-
Horsfall protein(a urinary glycoprotein
normally secreted by the cells of ascending
thick limb and distal tubules) in conjunction
with other plasma proteins.
171

172. • Other findings in ischemic ATI are interstitial
edema and accumulations of leukocytes
within dilated vasa recta.
• Evidence of epithelial regeneration in the form
of flattened epithelial cells with
hyperchromatic nuclei and mitotic figures.
172

173. Toxic ATI
• manifested by acute tubular injury, most
obviousin the proximal convoluted tubules.
• On histologic examination the tubular necrosis
may be nonspecific, but it is somewhat distinctive
in poisoning with certain agents.
• With mercuric chloride,for example, severely
injured cells may contain large acidophilic
inclusions. Later, these cells become necrotic, are
desquamated into the lumen, and may undergo
calcification.
173

174. • Carbon tetrachloride poisoning, in contrast, is
characterized by
• the accumulation of neutral lipids in injured cells;
again, suchfatty change is followed by necrosis.
• Ethylene glycol produces marked ballooning and
hydropic or vacuolar degeneration of proximal
convoluted tubules.
• Calcium oxalate crystals are often also found in
tubular lumens in ethylene glycol poisoning.
174

175. Clinical course
• Highly variable:divided into three stages.
1) • Initiation phase, lasting about 36 hours
175

176. 2) Maintenance phase is characterized by
sustained decreases in urine output to
between 40 and 400 mL/day (oliguria), salt
and water overload, rising BUN
concentrations,hyperkalemia, metabolic
acidosis, and other manifestations of uremia.
176

177. 3) Recovery phase: steady increase in urine
volume that may reach up to 3 L/day.
The tubules are still damaged, so large amounts
of water, sodium, and potassium are lost in
the flood of urine. Hypokalemia,rather than
hyperkalemia.
177

178. Summary
• Acute Tubular Injury
• ■ Acute tubular injury is the most common cause
of acute kidney injury and attributed to ischemia
and/or toxicity from an endogenous or
exogenous substance.
■ Tubular epithelial cell injury and altered intrarenal
hemodynamics are the primary contributors to
acute tubular injury.
■ The clinical outcome is determined by the
magnitude and duration of acute tubular injury.
178

179. ATN
179

180. 181

181. Chronic glomerulonephritis
• End-stage glomerular disease of different
types of glomerulonephritis
• Poststreptococcal glomerulonephritis  rare
antecedent of chronic glomerulonephritis
182

182. • Crescentic glomerulonephritis  usually
progress to chronic glomerulonephritis
• Membranous nephropathy, MPGN, IgA
nephropathy, and FSGS all may progress to
chronic renal failure
183

183. 184

184. 185

185. • Glomerular histology depends on stage of
disease
• In early cases, glomeruli may show evidence
of primary disease (membranous nephropathy
or MPGN)
186

186. Clinical Course
• Chronic glomerulonephritis develops
insidiously
• Slowly progresses to renal insufficiency or
death from uremia
187

187. • Presentations - loss of appetite, anemia,
vomiting, or weakness
• Proteinuria, hypertension, or azotemia on
routine medical examination
• Nephrotic patients - glomeruli become
obliterated and GFR decreases, protein loss in
urine diminishes
188

188. Lupus nephritis (SLE nephritis)
• Inflammation of kidneys caused by systemic
lupus erythematosus (SLE)
• Secondary glomerulonephritis
189

189. Class I disease (minimal mesangial GN)
• Histology - normal appearance
under light microscope
• Mesangial deposits are visible
under electron microscope
• Urinalysis is normal.
190

190. Class II disease (mesangial
proliferative GN)
• Mesangial hypercellularity and
matrix expansion
• Microscopic haematuria
with/without proteinuria
• HTN, nephrotic syndrome, and
acute kidney insufficiency are very
rare
191

191. Class III disease (focal proliferative
GN)
• Proliferation of endothelial and mesangial cells
• Neutrophilic infiltration
• Fibrinoid necrosis
• Capillary thrombosis
192

192. • Electron microscopy - subendothelial deposits
are noted
• Immunofluorescence – positive for IgG, IgA,
IgM, C3, and C1q.
• Clinically, haematuria and proteinuria with or
without nephrotic syndrome, hypertension,
and elevated serum creatinine
193

193. Class IV disease (diffuse proliferative
nephritis)
• Most severe, most common subtype
• > 50% of glomeruli are involved
• Lesions can be segmental or global, and active
or chronic, with endocapillary or extracapillary
proliferative lesions
194

194. • EM - subendothelial deposits and some
mesangial changes may be present
• Clinically, haematuria and proteinuria with
nephrotic syndrome, HTN,
hypocomplementemia, elevated anti-dsDNA
titres and elevated serum creatinine
195

195. Class V disease (membranous GN)
• Characterized by diffuse thickening of
glomerular capillary wall (segmentally or
globally), with diffuse membrane thickening,
and subepithelial deposits
196

196. • Clinically, presents with signs of nephrotic
syndrome
• Microscopic haematuria and hypertension
may also been seen
• Thrombotic complications - renal vein
thromboses or pulmonary emboli
197

197. Wire loop lesion
• Massive subendothelial immune complex
deposition with capillary wall thickening
• Seen in classes III, IV & V
198

198. 199

199. Renal Calculi, Stones
Types, causes and morphology
Dr Moni Subedi
200

200. • Renal stones are formed by precipitation of
urinary constituents .
• Men are affected more than women, the peak
age 20 and 30 years.
201

201. Pathogenesis
• The function of kidney is to conserve water and excreation of low
solubility material
• Balance between two opposing requirements affected by diet ,
environment , physical activities .
• Increased urinary concentration of the stones' constituents, exceeds
their solubility (supersaturation).
• A low urine volume in some metabolically normal patients may also
favor supersaturation.
202

202. Types of renal stones
• Calcium stone
• Struvite stone (triple stones )
• Uric acid stone
• Cystine stone
203

203. Calcium stone
• Calcium stones are either calcium oxalate or calcium phosphate or a mixture of
the two .
• Common type of stone -75% of all urinary calculi
• Deposited in acidic urine
• More common in male
• Dumbell shaped
204

204. Causes
• Hypercalcemia and hypercalciuria-
• hyperparathyroidism
• diffuse bone disease
• sarcoidosis
• About 55% have hypercalciuria without hypercalcemia.
• Caused by hyperabsorption of calcium from the intestine (absorptive hypercalciuria),
an intrinsic impairment in renal tubular reabsorption of calcium (renal
hypercalciuria), or idiopathic fasting hypercalciuria with normal parathyroid function.
• As many as 20% of calcium oxalate stones are associated with increased uric acid
secretion (hyperuricosuric calcium nephrolithiasis), with or without hypercalciuria.
205

205. 206

206. Struvite stone
• Second most common stone-15%
• Made up of magnesium, ammonium and phosphate
• Result of urinary tract infection with urea –splitting bacteria ,usually
proteus and some staphylococci
• They grow to a large size filling renal pelvis and calyces called stage
horn calculus since its appears like the branching horn of a stag
• Deposits in alkaline urine
207

207. 208

208. Uric acid stone
• 5-10%
• Occurs in hyperuricemia, such as gout, and diseases involving rapid cell
turnover, such as the leukemias
• More than half of all patients with uric acid calculi have neither
hyperuricemia nor increased urinary excretion of uric acid.
• In such there is unexplained tendency to excrete urine of pH below 5.5
predispose to uric acid stones, because uric acid is insoluble in acidic urine.
• Radiolucent
209

209. 210

210. Cystine stones
• 1-5%
• Caused by genetic defects in the renal reabsorption of amino acids, including
cystine, leading to cystinuria.
• Stones form at low urinary pH.
• Lemon yellow colour
211

211. 212

212. Morphology
• Unilateral in about 80% of patients.
• Sites- for their formation are within the renal calyces and pelves and in the
bladder.
• Renal pelvis -small, having an average diameter of 2 to 3 mm.
• Smooth contours take the form of an irregular, jagged mass of spicules.
• Many stones are found within one kidney.
• Progressive accretionan( increase by natural growth ) of salts leads to the
development of branching structures known as staghorn calculi, which create a
cast of the pelvic and calyceal system
213

213. Symptoms
• Severe pain in the side and back, below the
ribs
• Pain that spreads to the lower abdomen
and groin
• Pain on urination
• Pink, red or brown urine
• Cloudy or foul-smelling urine
• Nausea and vomiting
• Persistent need to urinate
214

214. 215

215. 216

216. GLOMERULAR LESIONS
ASSOCIATED WITH
SYSTEMIC DISEASES
217

217. Lupus nephritis
• Renal involvement of systemic lupus
erythromatosis are termed as Lupus nephritis.
• Lupus nephritis affects up to 50% of SLE patients.
• The principal mechanism of injury is immune
complex deposition in the glomeruli, tubular or
peritubular capillary basement membranes
218

218. morphologic classification
Five patterns are recognized
• minimal mesangial (class I)
• mesangial proliferative (class II)
• focal proliferative (class III)
• diffuse proliferative (class IV)
• membranous (class V)
219

219. Minimal mesangial (class I)
Light microscopy-no or slight abnormality.
Electron microscopy or immunofluorescence-show
deposits within the mesangium which consist of
IgG and C3.
220

220. Mesangial proliferative (class II)
is seen in 10% to 25% of patients
• LM-increase in mesangial cells and mesangial
matrix
• EM-granular mesangial deposits of IgG and C3 .
221

221. Focal proliferative
glomerulonephritis (class III)
• is seen in 20% to 35% of patients
• 50% involvement of all glomeruli.
222

222. Morphology
The lesions may be segmental (affecting only a
portion of the glomerulus) or global (involving the
entire glomerulus).
• -crescent formation
• -fibrinoid necrosis
• -proliferation of endothelial and mesangial cells
• -infiltrating leukocytes, and eosinophilic deposits
or intracapillary thrombi
223

223. Diffuse proliferative
glomerulonephritis (class IV)
LM-is the most severe form of lupus nephritis
• occurring in 35% to 60% of patients.
• Diffuse proliferation of endothelial,
mesangial and epithelial cells
• Entire glomerulus is frequently affected but
segmental lesions also may occur.
224

224. Membranous glomerulonephritis
(class V
LM-is characterized by diffuse thickening of
the capillary walls
seen in 10% to 15% of lupus nephritis
EM-subendothelial deposits of immune
complexes containing IgG ,IgM and C3
225

225. Diabetic nephropathy
• Renal involvement in complication of DM
• Advanced or end-stage kidney disease
occurs in as many as 40% of both insulin-
dependent type 1 diabetics and type 2
diabetics
226

226. Pathogenesis
• Hyperglycemia –glomerular hypertension –
renal hyperperfusion –deposition of proteins
in the mesangium –glomerulosclerosis –
renal failure .
227

227. The morphologic changes in the glomeruli
include
• (1) capillary basement membrane
thickening
• (2) diffuse mesangial sclerosis
• (3) nodular glomerulosclerosis.
228

228. Capillary Basement Membrane
Thickening.
• Widespread thickening of the glomerular
capillary basement membrane (GBM)
• Pure capillary basement membrane thickening
can be detected by electron microscopy.
229

229. Diffuse Mesangial Sclerosis.
• Diffuse increase in mesangial matrix
• Mild proliferation of mesangial cells early in the disease process
• As the disease progresses, the expansion of mesangial areas can extend
to nodular configurations.
• The mesangial increase is typically associated with the overall
thickening of the GBM.
• The matrix depositions are PAS-positive
230

230. 231

231. 232

232. 233

233. Nodular Glomerulosclerosis.
 Known as intercapillary glomerulosclerosis or Kimmelstiel-Wilson disease.
 Glomerular lesions form of ovoid or spherical, laminated, nodules of matrix situated in the
periphery of the glomerulus.
 Nodules is surrounded by peripherally by glomerular capillary loops.
 Nodular lesions enlarge ,compress the glomerular capillaries and obliterate the glomerular
tuft .
 These nodular lesions are accompanied by prominent accumulations of hyaline material in
capillary loops (“fibrin caps”) or adherent to Bowman's capsules (“capsular drops-)
 Consequence of the glomerular and arteriolar lesions, the kidney suffers from ischemia,
develops tubular atrophy and interstitial fibrosis and undergoes contraction in size
 -PAS-positive. 234

234. 235

235. 236

236. Renal atherosclerosis and
arteriolosclerosis
• constitute part of the macrovascular disease
in diabetics.
• Hyaline arteriolosclerosis affects not only
the afferent but also the efferent arteriole
237

237. Henoch-Schönlein Purpura
• purpuric skin lesions characteristically
involving the extensor surfaces of arms and
legs as well as buttocks
• abdominal manifestations including pain,
vomiting, and intestinal bleeding
• renal abnormalities
• IgA is deposited in the glomerular
mesangium in a distribution
• most common in children 3 to 8 years old
238

238. 239

239. Morphology
• LM-mild focal mesangial proliferation to
diffuse mesangial proliferation and
endocapillary to crescentic
glomerulonephritis.
• EM-deposition of IgA, sometimes with IgG
and C3, in the mesangial region.
240

240. 241

241. Nephrosclerosis
242

242. • Nephrosclerosis is the term used for the renal
pathology associated with sclerosis of renal
arterioles and small arteries and is strongly
associated with hypertension.
243

243. • Affected vessels have thickened walls and
consequently narrowed lumens, changes that
result in focal parenchymal ischemia.
244

244. Pathogenesis
• Two processes participate in the arterial lesions:
• •1) Medial and intimal thickening, as a response
to hemodynamic changes, aging, genetic defects,
or some combination of these.
• •2) Hyalinization of arteriolar walls, caused by
extravasation of plasma proteins through injured
endothelium and by increased deposition of
basement membrane matrix
245

245. Morphology
• Kidneys : either normal or moderately
reduced in size,
• With average wt betn 110 and 130 gm.
• The cortical surfaces have a fine, even
granularity that resembles grain leather (Fig.
20-36). The loss of mass is due mainly to
cortical scarring and shrinking.
246

246. • Histologic examination: narrowing of the
lumens of arterioles and small arteries, caused
by thickening and hyalinization of the walls
(hyaline arteriolosclerosis) (Fig. 20-37).
• fibroelastic hyperplasia
247

247. • There is patchy ischaemiac atrophy which
consists of
• (1) foci of tubular atrophy and interstitial fibrosis
and
• (2) a variety of glomerularalterations. The latter
include collapse of the GBM, deposition of
collagen within Bowman space, periglomerular
fibrosis, and total sclerosis of glomeruli.
• Ischemic changes: affect large areas of
parenchyma, produce wedge shaped infarcts or
regional scars.
248

248. C/F
• Renal insufficiencyor uremia
• Three groups of hypertensive patients with
nephrosclerosis are at increased risk of
developing renal failure:
249

249. • 1)People of African descent,
• 2) people with severe blood pressure
elevations,
• 3)persons with a second underlying disease,
especially diabetes.
250

250. Close-up of the gross appearance of the cortical surface in
benign nephrosclerosis illustrating the fine, leathery granularity of the surface
251

251. Figure 20-37 Hyaline arteriolosclerosis. High-power view of two
arterioles
with hyaline deposition, marked thickening of the walls, and a
narrowed
lumen.
252

252. Malignant Nephrosclerosis
• Malignant nephrosclerosis is a renal vascular
disorder associated with malignant or
accelerated hypertension.
• Develops suddenly in previously normotensive
individuals but more often is superimposed on
preexisting essential hypertension, secondary
forms of hypertension, or an underlying
chronic renal disease, particularly
glomerulonephritis or reflux nephropathy.
253

253. Pathogenesis
• The fundamental lesion in malignant
nephrosclerosis is vascular injury.
• Longstanding hypertension, arteritis, or a
coagulopathy, alone or in combination.
254

254. • Initiating event injures endothelium and
results in increased permeability of the small
vessels to fibrinogen and other plasma
proteins, focal death of cells of the vascular
wall, and platelet deposition.
• Fibrinoid necrosis of arterioles and small
arteries, with activation of platelets and
coagulation factors causing intravascular
thrombosis.
255

255. Morphology
• The kidney size varies depending on the
duration and severity of the hypertensive
disease.
• Small, pinpoint petechial hemorrhages may
appear on the cortical surface from rupture of
arterioles or glomerular capillaries, giving the
kidney a peculiar “flea-bitten” appearance.
• Two histologic alterations characterize blood
vessels in malignant hypertension (Fig. 20-38):
256

256. 1) Fibrinoid necrosis of arterioles:
In this form of necrosis,
• Cytologic detail is lost and the vessel wall takes
on a smudgy eosinophilc appearance due to
fibrin deposition.
• Minimal inflammation.
• Sometimes the glomeruli become necrotic and
infiltrated with neutrophils, and the glomerular
capillaries may thrombose.
257

257. 2) In the interlobular arteries and arterioles:
Intimal thickening caused by a proliferation of
elongated, concentrically arranged smooth
muscle cells, together with fine concentric
layering of collagen and accumulation of pale-
staining material that probably represents
deposition of proteoglycans and plasma proteins.
This alteration has been referred to as onion-
skinning because of its concentric appearance.
• The lesion, also called hyperplastic arteriolitis,
correlates with renal failure.
258

258. • There may be superimposed intraluminal
thrombosis.
• The arteriolar and arterial lesions result in
considerable narrowing of all vascular lumens,
ischemic atrophy and, at times, infarction
distal to the abnormal vessels.
259

259. Figure 20-38 Accelerated
hypertension. A, Fibrinoid necrosis of
afferent arteriole (PAS stain
260

260. B, Hyperplastic arteriolitis (onion-skin
lesion).
261

261. Clinical Features. The full-blown
syndrome of malignant
hypertension
• Systolic pressures > 200 mm Hg and diastolic p>
120 mHg, papilledema, retinal hemorrhages,
encephalopathy, cardiovascular abnormalities,
and renal failure.
• Early symptoms : ↑ed intracranial pressure and
include headaches, nausea, vomiting,and visual
impairments, particularly scotomas or spots
before the eyes.
• “Hypertensive crises” characterized by loss of
consciousness or even convulsions.
262

262. Renal artery stenosis
• Unilateral renal artery stenosis is responsible
for 2% to 5% of hypertension cases, and is
important to recognize because it is
potentially curable by surgery.
263

263. Pathogenesis
• Hypertension secondary to renal artery
stenosis is caused by increased production of
renin from the ischemic kidney.
264

264. Morphology
• The most common cause of renal artery
stenosis (70% of cases) is narrowing at the
origin of the renal artery by an atheromatous
plaque. This occurs more frequently in men,
and the incidence increases with advancing
age and diabetes mellitus.
265

265. • The plaque is usually concentrically placed, and
superimposed thrombosis often occurs.
• The second most frequent cause of stenosis is
fibromuscular dysplasia of the renal artery.
• This heterogeneous entity is characterized by
fibrous or fibromuscular thickening that may
involve the intima, the media, or the adventitia of
the artery (Fig.20-39).
• Stenoses are more common in women and tend
to occur in younger age groups (i.e., in the third
and fourth decades).
266

266. • Ischemic kidney is reduced in size and shows
signs of diffuse ischemic atrophy, with
crowded glomeruli, atrophic tubules,
interstitial fibrosis, and focal inflammatory
infiltrates.
• In contrast, the contralateral nonischemic
kidney may show more severe
arteriolosclerosis, depending on the severity
of the hypertension.
267

267. C/f
• Few distinctive features suggest the presence of renal
artery stenosis, and in general, these patients
• resemble those with essential hypertension.
• On occasion, a bruit can be heard on auscultation of
the affected kidneys.
• Elevated plasma or renal vein renin, response to
angiotensinconverting enzyme inhibitor, renal scans,
and intravenous pyelography may aid with diagnosis,
but arteriography is required to localize the stenotic
lesion.
• The cure rate after surgery is 70% to 80% in well-
selected cases.
268

268. Figure 20-39 Fibromuscular dysplasia of the renal artery, medial type (elastic
tissue stain). The media shows marked fibrous thickening, and the lumen is
stenotic.
269

269. 270

270. Renal failure
271

271. • It is of two types:
- acute and chronic.
• Acute kidney injury (AKI) has replaced the
term ‘acute renal failure’.
• Chronic Kidney Disease (CKD) has replaced the
term ‘chronic renal failure’.
272

272. Acute Kidney Injury
(Acute Renal Failure)
• Definition:
– ARF is defined as an abrupt or rapid, reversible
decline in renal filtration function.
– It is marked by a rise in serum creatinine
concentration or azotemia.
273

273. • Azotemia:
- a rise in blood urea nitrogen [BUN] concentration.
• Normal values:
- BUN: 8-20 mg/dL
- serum creatinine: 0.7-1.4 mg/dL (males)
1.1 mg/dL (females)
274

274. • Patients with AKI may or may not have oliguria
and anuria.
• Oliguria: urine excretion <400 ml/day.
• Anuria: urine excretion <100 ml/day.
275

275. Classification:
• Prerenal:
- occurs in hypovolemic, cardiogenic and septic shock.
- Kidneys are normal.
• Renal (Intrinsic):
- in response to cytotoxic, ischemic, or inflammatory
insults to the kidney, with structural and functional
damage
• Postrenal:
- from obstruction to the passage of urine.
276

276. • Causes of Pre-renal ARF:
1. Volume depletion
• Renal losses (diuretics, polyuria)
• GI losses (vomiting, diarrhea)
• Cutaneous losses (burns)
• Hemorrhage
277

277. 2. Decreased cardiac output
• Heart failure
• Acute myocardial infarction
3. Systemic vasodilation
• Septic shock
• Anaphylactic shock
278

278. • Causes of intrinsic ARF:
– Glomerular diseases:
• Several types of glomerulonephritis
• Glomerular injury occur d/t reaction oxygen species
produced during inflammation.
– Injury to tubular epithelium by drugs (e.g.
aminoglycosides: gentamicin, amikacin), chemicals
(e.g. contrast material used in radiology),
septicemia, ischemia due to hypotension
279

279. • Causes of postrenal ARF:
– Ureteric obstruction (stones, tumors)
– Bladder neck obstruction (benign prostatic
hypertrophy, cancer of prostate)
– Urethral obstruction (strictures, tumors)
280

280. Chronic Kidney Disease
• Definition:
- CRF is defined as:
1. azotemia for > 3 months with or without kidney
damage, or
2. GFR <60 ml/minute/1.73 sqm for > 3 months
with or without kidney damage.
281
• Normal GFR: 125 mL/min (10% less for women),
or 180 L/day.

281. • Uremia may be present in CRF.
• Uremia: azotemia with symptoms and signs of
renal failure (nausea, vomiting, fatigue,
anorexia, very itchy skin, change in mental
status)
282

282. • End-stage renal disease: GFR is <5% of
normal. The patient requires kidney
transplantation or dialysis for survival.
283

283. Causes of CRF
1. Previous episodes of acute renal failure
2. Kidney diseases:
- polycystic kidney disease,
- glomerulonephritis,
- analgesic nephropathy due to daily ingestion of
analgesics for many years:
- Mechanism: Renal papillary necrosis occurs which is
d/t medullary ischaemia secondary to suppression of
prostaglandin synthesis.
284

284. 3. Systemic diseases:
- Diabetes:
Glomerular lesions occur: thickening of glomerular basement
membrane.
Hyaline arteriolosclerosis causes glomerular ischemia and
glomerulosclerosis.
- Hypertension:
Glomerular ischemia occurs d/t hyaline arteriolosclerosis.
Ischemia causes sclerosis in glomeruli (glomerulosclerosis).
Glomeruli lose function gradually.
285

285. Glomerulosclerosis
286

286. Complications of CRF
1. Anemia:
- due to reduced erythropoietin hormone
production by kidney.
(Erythropoietin is required for erythropoiesis.)
2. Hyperkalemia:
- K+ retention occurs b/o lack of glomerular and
tubular filtration.
- Because of acidosis, there is shift of K+ from
intracellular compartment to extracellular
compartment.
287

287. 3. Fluid overload:
- Pulmonary edema can occur.
288

288. 4. Severe osteoporosis (Renal
osteodystrophy/Metabolic bone disease):
- Decreased GFR causes decreased clearance of
phosphate leading to hyperphosphatemia.
- Hyperphosphatemia causes hypocalcemia.
- Hypocalcemia stimulates parathyroid glands.
- Increased secretion of PTH from parathyroid
glands causes increased bone resorption to bring
blood calcium level to its normal range.
- Excessive calcium resorption from bone makes
them osteoporotic.
289

289. - Due to pathology of renal parenchyma, vitamin D
can not be converted to its active form.
- Low vitamin D causes poor absorption of calcium
from GI tract resulting in hypocalcemia.
- Hypocalcemia stimulates parathyroid glands.
290

290. 5. Hyperphosphatemia causes Ca phosphate
precipitation in tissues.
6. Acidosis develops because hydrogen ions can
not be excreted by kidneys.
291

291. 7. Bleeding tendency:
- increased urea level causes platelet dysfunction.
292

292. • Thank You !!
293

293. Risk Factors for
Adverse Outcomes of CKD
AJKD 2002: 39(2) 294

294. Potential Risk Factors for
Susceptibility to and
Initiation of CKD
AJKD 2002: 39(2)
295

295. 296

296. Why Estimate GFR From SCr, Instead
of Using SCr for Kidney Function?
*B = black; †W = all ethnic groups other than black.
GFR calculator available at: www.kidney.org/index.cfm?index=professionals. Accessed 3/28/05.
Age
Gend
er Race
SCr
(mg/dL)
eGFR
(mL/min/1.73
m2)
CKD
Stage
20 M B* 1.3 91 1
20 M W† 1.3 75 2
55 M W 1.3 61 2
20 F W 1.3 56 3
55 F B 1.3 55 3
50 F W 1.3 46 3
297

297. Evaluation of Proteinuria in Patients
Not Known to Have Kidney Disease
AJKD 2002: 39(2) 298

298. Why Classify Severity as the
Level of GFR?
AJKD 2002: 39(2) 299

299. Guideline 4.
Estimation of GFR
AJKD 2002: 39(2)
300

300. Guideline 4.
Estimation of GFR (cont’d)
AJKD 2002: 39(2) 301

301. Guideline 4.
Estimation of GFR (cont’d)
AJKD 2002: 39(2) 302

302. Advantages of Estimating GFR
Using Equations
AJKD 2002: 39(2) 303

303. Serum Creatinine
Corresponding to GFR of
60 mL/min/1.73 m2
AJKD 2002: 39(2)
304

304. Prevalence of Individuals at
Increased Risk for CKD
AJKD 2002: 39(2)
305

305. 306

306. 307

307. Drug Induced Tubulointerstitial
Nephritis
• Drugs can produce renal injury by:
–Triggering interstitial immunological
reaction acute hypersensitivity nephritis
induced by methicillin
308

308. –Causing acute renal failure
–Causing subtle but cumulative injury to
tubules resulting in chronic renal
insufficiency
309

309. Acute Drug-Induced Interstitial
Nephritis
• Occurs with synthetic penicillins (methicillin,
ampicillin), other synthetic antibiotics
(rifampin), diuretics (thiazides), NSAIDs, and
miscellaneous drugs (allopurinol, cimetidine)
310

310. • Begins about 15 days after exposure to drug
• Characterized by fever, eosinophilia, rash in
about 25% of patients, and renal
abnormalities (hematuria, mild proteinuria,
and leukocyturia)
311

311. • 50% of cases  rising serum creatinine level
or acute renal failure with oliguria develops
312

312. Pathogenesis
• Immune response  idiosyncratic and not
dose-related
• Drugs act as haptens, bind to some
cytoplasmic or extracellular component of
tubular cells and become immunogenic
313

313. • Resultant injury is due to IgE and/or cell-
mediated immune reactions to tubular cells or
their basement membranes
314

314. Morphology
• Interstitium
–Edema and infiltration of lymphocytes and
macrophages
–Eosinophils and neutrophils may be present
–Non-necrotizing granulomas containing
giant cells may be seen
315

315. • Tubules
–Lymphocytic infiltration
–Variable degrees of tubular necrosis and
regeneration
• Glomeruli
–Normal
–NSAIDs may cause minimal-change disease
and nephrotic syndrome
316

316. Analgesic Nephropathy
• Chronic renal disease caused by excessive
intake of analgesic mixtures
• Characterized morphologically by chronic
tubulointerstitial nephritis and renal papillary
necrosis
317

317. Pathogenesis
• Papillary necrosis occurs first, and cortical
tubulointerstitial nephritis follows as a
consequence of impeded urine outflow
318

318. • Phenacetin metabolite acetaminophen
reduces glutathione from cells and injures
cells by generation of oxidative metabolites.
319

319. • Aspirin potentiates effect by inhibiting
vasodilatory effects of prostaglandins,
predisposing papillae to ischemia
• Papillary damage  combination of direct
toxic effects of phenacetin metabolites and
ischemic injury
320

320. Morphology
• Gross  kidneys  normal or slightly reduced
in size
• Cortex  depressed areas representing
cortical atrophy overlying necrotic papillae
• Papillae show various stages of necrosis,
calcification, fragmentation, and sloughing
321

321. • Microscopic  papillary changes in early
cases  patchy necrosis
• Advanced form  entire papilla is necrotic,
remaining structureless mass (ghosts of
tubules) and foci of dystrophic calcification
322

322. • Segments of entire portions of papilla may be
sloughed and excreted in urine
• Cortical changes  loss and atrophy of
tubules and interstitial fibrosis and
inflammation
• Cortical columns of Bertin are spared from
atrophy
323

323. Obstructive Uropathy
• Obstruction of urinary outflow increases
susceptibility to infection and stone
formation, and unrelieved obstruction leads to
permanent renal atrophy, termed
hydronephrosis or obstructive uropathy
324

324. • Obstruction  sudden or insidious, partial or
complete, unilateral or bilateral
• May occur at any level of the urinary tract
from urethra to renal pelvis
• Can be caused by lesions that are intrinsic to
urinary tract or extrinsic lesions that compress
ureter
325

325. Causes of
obstructive
uropathy
326

326. Hydronephrosis
• Dilation of renal pelvis and calyces associated
with progressive atrophy of kidney due to
obstruction to the outflow of urine
• Affected calyces and pelvis become dilated
327

327. • High pressure in pelvis is transmitted back
through collecting ducts into cortex, causing
renal atrophy, compression of renal
vasculature of the medulla  diminution in
inner medullary blood flow
328

328. • Initial functional alterations  impaired
concentrating ability of tubules
• Later  GFR begin to fall
• Obstruction also triggers interstitial
inflammatory reaction, leading to interstitial
fibrosis
329

329. Morphology
• Sudden and complete obstruction 
glomerular filtration is reduced
• Leads to mild dilation of pelvis and calyces
and sometimes to atrophy of renal
parenchyma
• Subtotal/intermittent obstruction 
glomerular filtration is not suppressed, and
progressive dilation
330

330. Progressive blunting of apices of pyramids,
eventually become cupped
Advanced cases  kidney transformed into thin-
walled cystic structure with parenchymal
atrophy, total obliteration of pyramids, and
thinning of cortex
331

331. Clinical Features
• Acute obstruction  pain due to distention of
collecting system or renal capsule
• Calculi in ureters give rise to renal colic, and
prostatic enlargements to bladder symptoms.
332

332. • Unilateral complete or partial hydronephrosis
may remain silent for long periods
• Bilateral partial obstruction  earliest
manifestation polyuria and nocturia due to
inability to concentrate urine
333

333. • Complete bilateral obstruction results in
oliguria or anuria and is incompatible with
survival unless obstruction is relieved
334

334. 335

335. Classification of kidney tumors
• Renal cell tumours
–Benign
• Papillary adenoma
• Oncocytoma
–Malignant
• Clear cell renal cell carcinoma
• Multilocular clear cell renal cell carcinoma
• Papillary renal cell carcinoma
336

336. • Chromophobe renal cell carcinoma
• Carcinoma of the collecting ducts of
Bellini
• Renal medullary carcinoma
• Metanephric tumours
–Metanephric adenoma
–Metanephric adenofibroma
–Metanephric stromal tumour
337

337. • Nephroblastic tumours
–Nephrogenic rests
–Nephroblastoma
• Mesenchymal tumours
–Occurring Mainly in Children
• Clear cell sarcoma
• Rhabdoid tumour
• Ossifying renal tumour of infants
338

338. –Occurring Mainly in Adults
• Leiomyosarcoma (including renal vein)
• Angiosarcoma
• Rhabdomyosarcoma
• Malignant fibrous histiocytoma
• Metastatic tumours
339

339. Renal Cell Carcinoma
• Tumors occur most often in older individuals,
usually in sixth and seventh decades of life
• Male:Female - 2 : 1
340

340. Risk factor
• Tobacco  most significant risk factor,
incidence is double in smokers
• Obesity (particularly in women)
• Hypertension
• Unopposed estrogen therapy
• Exposure to asbestos, petroleum products,
and heavy metals
341

341. • Most renal cancer is sporadic
• Autosomal dominant familial cancers may
occur in younger individuals which includes:
1. Von Hippel-Lindau (VHL) syndrome:
 develop renal cysts and bilateral, often
multiple, renal cell carcinomas
 VHL gene  in both familial and sporadic
clear cell tumors.
342

342. 2. Hereditary (familial) clear cell carcinoma,
without other manifestations of VHL variant.
3. Hereditary papillary carcinoma, manifested
by multiple bilateral tumors with papillary
histology.
343

343. Clear cell carcinoma
• Most common type (70%-80%)RCC
• Cells have clear or granular cytoplasm and are
nonpapillary
• 95% of cases are sporadic, few are familial
344

344. • In 98% of cases  loss of sequences on short
arm of chromosome 3 in the region of VHL
gene
• Second nondeleted allele of VHL gene shows
somatic mutations
345

345. Papillary carcinoma
• 10% to 15% of renal cancers
• Papillary growth pattern
• Common cytogenetic abnormalities 
–Trisomies 7, 16, and 17
–Loss of Y in male patients in sporadic form
–Trisomy 7 in the familial form
• Frequently multifocal in origin
346

346. Chromophobe renal carcinoma
• 5% of renal cell cancers
• Composed of cells with prominent cell
membranes and pale eosinophilic cytoplasm,
with halo around the nucleus
• Excellent prognosis compared with that of the
clear cell and papillary cancers
347

347. Collecting duct (Bellini duct)
carcinoma
• Approx. 1% or less of renal epithelial
neoplasms
• Arise from collecting duct cells in the medulla.
• Histologically  characterized by nests of
malignant cells enmeshed within prominent
fibrotic stroma
348

348. Morphology
• Commonly arise in poles of kidney
Clear cell carcinomas
–Arise from proximal tubular epithelium
–Usually solitary unilateral lesions
–Spherical masses, composed of bright
yellow-gray-white tissue
349

349. –Yellow color is due to lipid accumulations in
tumor cells
–Margins  sharply defined and confined
within the renal capsule
350

350. Microscopic
• Solid to trabecular (cordlike) or tubular
pattern of growth
• Tumor cells  rounded or polygonal shape
and abundant clear or granular cytoplasm
• Tumors have delicate branching vasculature
and may show cystic as well as solid areas
351

351. Clear cell carcinomas
352

352. Papillary tumors
• Arise from distal convoluted tubules
• Can be multifocal and bilateral
• Hemorrhagic and cystic
• Most common type of renal cancer in patients
who develop dialysis-associated cystic disease
353

353. Microscopic
• Composed of cuboidal or low columnar cells
arranged in papillary formations
• Psammoma bodies may be present.
• Stroma is usually scanty but highly
vascularized.
354

354. Chromophobe renal carcinoma
• Made up of pale eosinophilic cells, often with
perinuclear halo
• Arranged in solid sheets with concentration of
largest cells around blood vessels
355

355. Collecting duct carcinoma
• Rare variant showing irregular channels lined
by highly atypical epithelium with a hobnail
pattern
356

356. • Sarcomatoid changes arise infrequently in all
types of renal cell carcinoma
• One of the characteristics of renal cell
carcinoma  tendency to invade the renal
vein and grow as a solid column of cells within
this vessel
357

357. • Further growth may produce a continuous
cord of tumor in the inferior vena cava that
may extend into the right side of the heart
358

358. Clinical Features
• Three classic diagnostic features of renal cell
carcinoma  costovertebral pain, palpable
mass, and hematuria
• Paraneoplastic syndromes associated with RCC
 polycythemia, hypercalcemia,
hypertension, hepatic dysfunction,
feminization or masculinization, Cushing
syndrome, eosinophilia, leukemoid reactions,
and amyloidosis.
359

359. • common locations of metastasis lungs
(>50%) and bones (33%), followed by regional
lymph nodes, liver, adrenal, and brain.
360