RENAL LECTURE NOTES Flashcards
(99 cards)
1
Q
Blood Vessels
l ___________ – most richly vascularized part;
receives 90% of total renal blood supply
l Renal artery–> interlobar arteries –>arcuate arteries –>interlobular arteries–> l Afferent arterioles enter glomerular tuft; subdivide into 20 to 40 capillary loops
l Capillary loops merge to exit as efferent arterioles
A
Cortex
2
Q
What is the blood flow of the kidney?
A
l Renal artery–> interlobar arteries –>arcuate arteries –>interlobular arteries–> l Afferent arterioles enter glomerular tuft; subdivide into 20 to 40 capillary loops
Note: l Capillary loops merge to exit as efferent arterioles
3
Q
Blood Vessels
l Efferent arterioles from superficial nephrons form _____________
A
peritubular vascular network
4
Q
l Deeper juxtamedullary glomeruli give rise to ____________
A
vasa recta
5
Q
l Vasa recta descend as straight vessels to supply _____________
A
outer and inner medulla
6
Q
l Anastomosing network of capillaries lined by fenestrated endothelium invested by two layers of epithelium
l Visceral epithelium – part of the capillary wall; separated from endothelial cells by a basement membrane
l Parietal epithelium – lines the urinary space (cavity in which plasma filtrate first collects)
A
Glomeruli
7
Q
____________– part of the capillary wall; separated from endothelial cells by a basement membrane
)
A
l Visceral epithelium
8
Q
____________ – lines the urinary space (cavity in which plasma filtrate first collects
A
l Parietal epithelium
9
Q
Glomerular capillary wall – filtering membrane and consists of:
A
- Endothelial cells
- Glomerular basement membrane (GBM)
– lamina densa,
lamina rara interna
and externa
- Visceral epithelial cells (podocytes)
– foot processes and filtration slits
- Mesangial cells – lie between capillaries; basement membrane-like mesangial matrix
10
Q
§ Contractile, phagocytic, capable of proliferation, lay down both matrix and collagen, secrete biologically active mediators
§ Important players in many forms of glomerulonephritis
A
Mesangial cells:
11
Q
Glomeruli Major characteristics of normal glomerular filtration:
A
§ High permeability to water and small solutes
§ Impermeability to proteins (albumin)
– glomerular barrier function (size- and chargedependent)
12
Q
________________- is important for the maintenance of glomerular barrier function
l Proteins located in slit diaphragm control glomerular permeability
l Mutations in genes encoding proteins give rise to nephrotic syndrome
A
l Visceral epithelial cell (slit diaphragm)
13
Q
_______________
: l Reabsorption of 2/3 of filtered Na, H2O, glucose, K, phosphate, amino acids and proteins
l Vulnerable to ischemic damage
l Toxins are frequently reabsorbed rendering it susceptible to chemical injury
A
Tubules Proximal tubules
14
Q
Tubules Juxtaglomerular apparatus:
A
l JG cells – modified smooth muscle cells in the media of afferent arteriole; produce renin
l Macula densa
l Lacis cells or nongranular cells – resemble mesangial cells
15
Q
________- – modified smooth muscle cells in the media of afferent arteriole; produce renin
A
JG cells
16
Q
_________________– resemble mesangial cells
A
Lacis cells or nongranular cells
17
Q
l Normal cortex: compact interstitial space occupied by peritubular capillaries and fibroblast-like cells
l Expansion of the cortical interstitium is abnormal (edema or inflammatory cells)
A
Interstitium
18
Q
___________– elevation of BUN and creatinine levels;
related to decreased GFR
A
Azotemia
19
Q
_________– hypoperfusion of the kidneys (hemorrhage, shock, volume depletion, CHF) that impairs renal function in the absence of parenchymal damage
A
l Prerenal
20
Q
____________– urine flow obstruction below the level of kidney
A
l Postrenal
21
Q
___________
l Azotemia with S/Sx
l Characterized by failure of renal excretory function and metabolic and endocrine alterations
A
Uremia
22
Q
Principal Systemic Manifestations
of CRF and Uremia
Fluid and Electrolytes:
A
l Dehydration
l Edema
l Hyperkalemia
l Metabolic acidosis
23
Q
Calcium Phosphate and Bone:
A
l Hyperphosphatemia
l Hypocalcemia
l Secondary hyperparathyroidism
l Renal osteodystrophy
24
Q
Hematologic:______________
A
l Anemia l Bleeding diathesis
25
Cardiopulmonary:
l HPN
l CHF
l Cardiomyopathy
l Pulmonary edema
l Uremic pericarditis
26
Gastrointestinal:
l Nausea and vomiting l Bleeding l Esophagitis, gastritis, colitis
27
Neuromuscular: l
Myopathy l Peripheral neuropathy l Encephalopathy
28
Dermatologic:
l Sallow color
l Pruritus
l Dermatitis
29
CLINICAL MANIFESTATIONS OF RENAL DISEASES l Acute nephritic syndrome
l Nephrotic syndrome
l Rapidly progressive glomerulonephritis –
l Acute renal failure –
l Chronic renal failure
30
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ – nephritic syndrome with rapid decline (hours to days) in GFR
Rapidly progressive glomerulonephritis
31
\_\_\_\_\_\_\_\_\_\_\_\_\_\_ – oliguria or anuria with recent onset azotemia; can result from glomerular, interstitial, vascular or acute tubular injury
Acute renal failure
32
\_\_\_\_\_\_\_\_\_\_\_ – prolonged S/Sx of uremia; end result of all chronic renal parenchymal diseases
Chronic renal failure
33
Polyuria, nocturia, electrolyte disorders – \_\_\_\_\_\_\_\_\_\_\_\_\_\_
renal tubular defects
34
l Bacteriuria and pyuria – \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
UTI
35
l Renal colic, hematuria – \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
nephrolithiasis
36
l Asymptomatic hematuria or proteinuria \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
– subtle glomerular abnormalities
37
GLOMERULAR DISEASES Primary Glomerulopathies:
l Acute proliferative glomerulonephritis – postinfectious, other
l Rapidly progressive (crescentic) glomerulonephritis
l Membranous glomerulopathy
l Minimal change disease
l Focal segmental glomerulosclerosis
l Membranoproliferative glomerulonephritis
l IgA nephropathy
l Chronic glomerulonephritis
38
GLOMERULAR DISEASES
Systemic Diseases with Glomerular Involvement:
l SLE
l DM l
Amyloidosis
l Goodpasture syndrome
l Microscopic polyarteritis/polyangiitis
l Wegener granulomatosis
l Henoch-Schönlein purpura
l Bacterial endocarditis
39
GLOMERULAR DISEASES
Hereditary Disorders:
l Alport syndrome
l Thin basement membrane disease
l Fabry disease
40
Clinical Manifestations
Glomerular Syndromes:
l Nephritic syndrome
l Rapidly progressive glomerulonephritis
l Nephrotic syndrome
l Chronic renal failure
l Isolated urinary abnormalities: hematuria and/or subnephrotic proteinuria
41
Histologic Alterations
l Hypercellularity
l Basement membrane thickening
l Hyalinization and sclerosis
42
Histologic Alterations
- Hypercellularity
l Cellular proliferation of mesangial or endothelial cells
l Leukocytic infiltration
l Formation of crescents
l Proliferating parietal epithelial cells and infiltrating leukocytes
l Fibrin as well as tissue factor, IL-1, TNF, interferon- γ elicit crescentic response
43
Histologic Alterations –BM Thickening
Light microscopy: l\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
Electron microscopy:
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
Thickening of capillary walls (PAS stain)
* l Deposition of amorphous electron-dense material (immune complexes, fibrin, amyloid, cryoglobulins, abnormal fibrillary protein)
* l Thickening of the basement membrane in diabetic glomerulosclerosis
44
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
l Accumulation of homogeneous and eosinophilic materia
l l Hyalin - plasma proteins from circulating plasma into glomerular structures
l Consequence of endothelial or capillary wall injury;
end result of glomerular damage
l A common feature of **FSGS**
Hyalinosis:
45
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
l Accumulation of extracellular collagenous matrix
l Mesangium (DM) or capillary loops
l May result in obliteration of capillary lumina in affected glomeruli
Sclerosis:
46
\_\_\_\_\_\_\_\_\_ underlie most forms of **primary glomerulopathy** and **many of the secondary glomerular disorders**
Immune mechanisms
47
Immune Mechanisms of Glomerular Injury
l Antibody-Mediated Injury
l In Situ Immune Complex Deposition
l Circulating Immune Complex Deposition
l Cytotoxic Antibodies
l Cell-Mediated Immune Injury
l Activation of Alternative Complement Pathway (occurs in dense deposit disease)
48
\_\_\_\_\_\_\_\_\_\_\_\_\_\_
l In these forms of injury, antibodies react directly with intrinsic tissue antigen, or antigens "planted" in the glomerulus from the circulation
l Anti-GBM antibody induced nephritis
l Heymann nephritis (membranous glomerulopathy)
Immune Complex Deposition Involving **Intrinsic and in Situ Renal Antigens**
49
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
l Antibodies are directed against **intrinsic fixed antigens that are normal components of the GBM prope**r
l Anti-GBM antibodies **cross-react** with other BM: Goodpasture syndrome
l GBM antigen is a component of the noncollagenous domain of the alpha 3-chain of collagen type IV
Anti-GBM Antibody-Induced Nephritis:
50
l Diffuse **linear staining** for the antibodies by immunofluorescent techniques
l Characterized by severe crescentic glomerular damage and the clinical syndrome of RPGN
Anti-GBM Antibody-Induced Nephritis:
51
Immune Complex Deposition Involving Intrinsic and in Situ Renal \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
l Antibodies react in situ with antigens **not normally present in the glomerulus but are “planted” there**
l Cationic molecules; DNA, nucleosomes, other nuclear proteins; bacterial products; large aggregated proteins; immune complexes l **Granular staining** pattern by IF microscopy
Antigens Antibodies against Planted Antigens:
52
\_\_\_\_\_\_\_\_\_\_\_\_\_
l Presence of numerous electron-dense granular deposits (immune reactants) along the subepithelial aspect of basement membrane
l Membranous glomerulopathy
Heymann Nephritis:
53
Circulating Immune Complex
Nephritis
l Glomerular injury is caused by the trapping of
circulating Ag-Ab complexes within glomeruli
l Abs have no immunologic specificity for
glomerular constituents
l Complexes localize within the glomeruli due
to their physicochemical properties and
hemodynamic factors
l Antigens that trigger formation of circulating immune
complexes may be endogenous (SLE) or exogenous
(infections)
l Microbial antigens include bacterial products
(streptococci), HBsAg, Hepatitis C antigen, antigens
of T. pallidum, P. falciparum
l Tumor antigens also cause IC-mediated nephritis
l In many cases, inciting antigen is unknown
Circulating Immune Complex
Nephritis
54
Circulating Immune Complex
Nephritis
l Glomerulus:\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
l EM:\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
l IF: \_\_\_\_\_\_\_\_\_\_\_\_\_\_
* leukocytic infiltration and proliferation of mesangial and endothelial cells
* immune complexes as
electron-dense deposits
(mesangium, subendothelial,
subepithelial)
* ICs seen as granular
deposits along the basement
membrane, in mesangium or
both
55
Antibodies to Glomerular Cells
l Abs to mesangial cell antigens –\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
l Abs to endothelial cell antigens – \_\_\_\_\_\_\_\_\_\_\_\_\_\_
l Abs to podocyte components – \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
* mesangiolysis and mesangial cell proliferation
* endothelial injury and intravascular thrombosis
* proteinuria
56
Mechanisms of Progression in Glomerular Diseases
Two major histologic characteristics of progressive renal damage:
l Focal segmental glomerulosclerosis
l Tubulointerstitial fibrosis
57
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
l Proteinuria
l Sclerosis initiated by the adaptive change that occurs in unaffected glomeruli of diseased kidneys
l TGF-ß play a role in induction of sclerosis
l Contributing to progressive injury is the inability of podocytes to proliferate after injury
Focal Segmental Glomerulosclerosis
58
\_\_\_\_\_\_\_\_\_\_\_\_\_\_
l Component of many acute and chronic GN
l Contributes to progression in both immune and nonimmune glomerular diseases (DM)
l Factors that lead to tubulointerstitial injury: ischemia of tubule, acute and chronic inflammation in the adjacent interstitium, damage or loss of the peritubular capillary blood supply
Tubulointerstitial Fibrosis
59
l Hematuria, **red cell casts in the urine,** azotemia, oliguria, **mild to moderate HPN**
l Proteinuria and edema
l Glomerular diseases presenting with nephritic syndrome are **characterized by inflammation in the glomeruli**
l Characteristic of acute proliferative GN and **is an important component of crescentic GN**
l **May occur in multisystem diseases: SLE, microscopic polyangiitis**
Nephritic Syndrome
60
l **Diffuse proliferation of glomerular cells** with influx of leukocytes l Caused by immune complexes
l Inciting antigen may be exogenous (postinfectious glomerulonephritis) or endogenous (lupus nephritis)
Acute Proliferative (Poststreptococcal, Postinfectious) Glomerulonephritis
61
l Appears **1-4 weeks after a streptococcal infection of pharynx or skin (impetigo)**
l Occurs most frequently in children 6-10 years old
Poststreptococcal Glomerulonephritis
62
s Etiology and Pathogenesis:
l Group **A ß-hemolytic streptococci**
l **Immunologically-mediated**
l Elevated titers of Abs against streptococcal antigens
l Low serum complement levels (activation and consumption of complement components)
l Granular immune deposits in glomeruli and electron dense deposits immune complex mediated mechanism
Poststreptococcal Glomerulonephriti
63
Morphology:
l **Enlarged, hypercellular glomeruli** caused by: **infiltration by leukocytes, proliferation of endothelial and mesangial cells, crescent formation**
**l Capillary lumen obliteration**
**l Interstitial edema and inflammation**
**l Tubules with red cell casts**
Poststreptococcal Glomerulonephritis
64
l IF microscopy: granular deposits of IgG, IgM, and C3 in mesangium and along GBM
Poststreptococcal Glomerulonephritis
65
Poststreptococcal Glomerulonephritis
Electron Microscopy:
l Discrete, amorphous, electron dense deposits on epithelial side of membrane (“humps”)
l Subendothelial, intramembranous and mesangial deposits are also seen Acute proliferative glomerulonephritis.
A, Normal glomerulus.
B, Glomerular hypercellularity is due to intracapillary leukocytes and proliferation of intrinsic glomerular cells.
C, Typical electron-dense subepithelial "hump" and a neutrophil in the lumen.
66
Poststreptococcal Glomerulonephritis
Clinical Course:
l Malaise, fever, nausea, oliguria, **hematuria 1-2 weeks after recovery from a sore throat**
l Red cell casts in urine, mild proteinuria (\<1 gm/day)
l Periorbital edema, mild to moderate HPN l
Elevations of antistreptococcal Ab titers; decline in serum C3 l **95% of affected children recover**
67
l Occurs sporadically in association with bacterial infections (staph endocarditis), viral disease, parasitic infections
l Granular immunofluorescent deposits and subepithelial humps are present
Nonstreptococcal Acute Glomerulonephritis (Postinfectious Glomerulonephritis)
68
l A syndrome associated with severe glomerular injury
l Characterized clinically by **rapid and progressive loss of renal** function with **severe oliguria and signs of nephritic syndrome**
l If untreated, death from renal failure occurs within weeks to months
l Most common histologic picture: **crescents in most of the glomeruli**
Rapidly Progressive (Crescentic) Glomerulonephritis
69
Rapidly Progressive (Crescentic) Glomerulonephritis Classification (immunological findings) and Pathogenesis:
l Type I RPGN – anti-GBM antibody-induced disease
l Type II RPGN – immune complex-mediated disease
l Type III RPGN – pauci-immune type
70
Rapidly Progressive (Crescentic) Glomerulonephritis
l **All 3 types** may be associated with a **welldefined renal or extrarenal disease,** but in approximately **50% of cases**, the disorder is idiopathic
l The common denominator in all types of RPGN is \_\_\_\_\_\_\_\_\_\_\_\_\_\_
severe glomerular injury
71
Rapidly Progressive (Crescentic) Glomerulonephritis
l **Linear deposits of IgG and C3 in the GBM**
l **Anti-GBM antibodies cross-react with pulmonary alveolar bm Goodpasture syndrome**
l Tx: **Plasmapheresis** to remove circulating Abs combined with steroids and cytotoxic agents
l Goodpasture antigen is a peptide within the noncollagenous portion of the α3 chain of collagen type IV
Type I RPGN:
72
Rapidly Progressive (Crescentic) Glomerulonephritis
l Can be a **complication of any of the immune complex** nephritides: postinfectious GN, lupus nephritis, IgA nephropathy, Henoch-Schönlein purpura
l IF: **granular pattern of staining characteristic of immune complex deposition**
l Cellular proliferation within glomerular tuft and crescent formation
l Require tx of underlying disease
Type II RPGN:
73
Rapidly Progressive (Crescentic) Glomerulonephritis
l Lack of anti-GBM Abs or immune complexes by IF and EM
l Most patients have circulating ANCAs that produce cytoplasmic (c) or perinuclear (p) staining patterns
l Component of systemic vasculitis – Wegener granulomatosis or microscopic polyangiitis
l In many cases, pauci-immune crescentic GN is isolated and hence idiopathic
Type III RPGN:
74
Rapidly Progressive (Crescentic) Glomerulonephritis
Morphology:
l Glomeruli: focal necrosis, diffuse or focal endothelial proliferation, mesangial proliferation
l Distinctive crescents - obliterate Bowman space and compress the glomerular tuft
l Fibrin strands are prominent between the cellular layers in the crescents
75
Rapidly Progressive (Crescentic) Glomerulonephritis
Morphology:
l EM: \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
l IF:\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
1. ruptures in the GBM; allows leukocytes, proteins and inflammatory mediators to reach urinary space trigger crescent formation
2. granular immune deposits (immune complex-mediated cases); linear fluorescence for Ig and complement (Goodpasture syndrome); little or no deposition (pauci immune)
76
Nephrotic Syndrome -
Causes Primary Glomerular Disease: l
Membranous glomerulopathy
l Minimal change disease
l Focal segmental glomerulosclerosis
l Membranoproliferative glomerulonephritis
l Other proliferative glomerulonephritides (focal, pure mesangial, IgA nephropathy)
77
Nephrotic Syndrome -
Causes Systemic Diseases:
l DM
l Amyloidosis
l SLE
l Drugs (NSAIDs)
l Infections (malaria, syphilis, hepatitis B and C, HIV)
l Malignant disease (carcinoma, lymphoma)
l Miscellaneous (hereditary nephritis)
78
l Common cause of nephrotic syndrome in
**adults**
l Diffuse thickening of the glomerular capillary
wall and
l Accumulation of electron-dense, Igcontaining
deposits along the subepithelial
side of bm
Membranous Nephropathy
79
Membranous Nephropathy
Secondary Membranous Glomerulopathy: occurs in association with other systemic diseases
l Drugs (Penicillamine, Captopril, NSAIDs)
l Underlying malignant tumors (carcinomas of lung and colon; melanoma)
l SLE
l Infections (chronic hepatitis B, hepatitis C, syphilis, schistosomiasis, malaria)
l Other autoimmune disorders (thyroiditis) 85% idiopathic
80
Membranous Nephropathy
Etiology and Pathogenesis:
l Idiopathic membranous glomerulopathy, **like Heymann nephritis, is considered an autoimmune disease linked to susceptibility genes and caused by antibodies to a renal autoantigen**
l C5b-C9 activation of glomerular epithelial and mesangial cells liberate proteases and oxidants capillary wall injury protein leakage
81
Membranous Nephropathy
LM:
uniform, diffuse thickening of the glomerular capillary wall
82
Membranous Nephropathy
l BM material laid down between IC deposits, appearing as _______________ protruding from the GBM
irregular spikes
## Footnote
Note : l Spikes are best seen by silver stains
83
Membranous Nephropathy
l EM:
irregular dense deposits of immune complexes between bm and overlying epithelial cells (with **effaced foot processes)**
84
Membranous Nephropathy l
IF:
**granular deposits** contain both Igs and complement Characteristic granular immunofluorescent deposits of IgG along GBM.
85
Membranous Nephropathy Clinical Course:
Begins with** insidious onset of nephrotic syndrome or with non-nephrotic proteinuria (15% of patients)**
l Hematuria and mild HPN (15 - 35%)
l Nonselective proteinuria
l Indolent course
l Does not respond well to steroid
l Progression is associated with increasing sclerosis of glomeruli, rising serum creatinine and development of HPN
86
l Most frequent cause of nephrotic syndrome in
**children**
l Peak incidence: between **2 and 6 years**
l **Diffuse effacement of foot processes** of
**podocytes in glomeruli** that appear virtually
**normal by LM**
l Sometimes **follows a respiratory infection or
routine prophylactic immunization**
l Most characteristic feature: r**esponse to
corticosteroid therapy**
Minimal Change Disease
87
Minimal Change Disease
Pathogenesis:
l MCD involves some immune dysfunction,
resulting in the elaboration of a cytokine that
**damages podocyte**s and **causes proteinuria**
l Nephrotic syndrome resulting from mutations in
**nephrin and podocin (localized to the slit**
**diaphragm)** illustrates that structural defects of
the **podocyte are sufficient to cause marked**
**proteinuria** in the absence of an immune injury
88
Minimal Change Disease
Morphology:
l LM:\_\_\_\_\_\_\_\_\_\_\_\_\_\_
l EM: \_\_\_\_\_\_\_\_\_\_\_\_\_\_
l IF: \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
1. glomeruli normal
2. no electron-dense
material; uniform and
diffuse effacement of
foot processes
3. no immunoglobulin
or complement deposits
89
Minimal Change Disease
Clinical Course:
l** Renal function remains good** despite massive proteinuria
l Highly selective proteinuria (albumin)
l** Response to corticosteroid therapy**
l** Excellent long-term prognosis**
l MCD in adults** can be associated with Hodgkin
lymphoma**
l **Secondary MCD may follow NSAID therapy in
association with AIN**
90
l Characterized by **sclerosis of some**, **but not
all glomeruli**; in the affected glomeruli, only a
portion of the capillary tuft is involved
**l Accompanied by nephrotic syndrome**
**l Most common cause of nephrotic syndrome
in adults in the US**
Focal Segmental Glomerulosclerosis
91
FSGS occurs in the following settings:
l HIV infection, heroin addiction, sickle cell disease,
massive obesity
l As a secondary event in focal glomerulonephritis
(reflecting glomerular scarring)
l As a component of adaptive response to loss of
renal tissue
l In certain inherited forms of nephrotic syndrome
**l As a primary disease (idiopathic FSGS)**
92
Clinical signs differ from those of MCD in the
following respects:
l Higher incidence of hematuria, reduced GFR,
HPN
l Proteinuria is more often nonselective
l Poor response to steroid
l Progression to chronic kidney disease
93
Focal Segmental Glomerulosclerosis
Morphology:
l EM: \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
l IF:\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
1. l **Collapse of BMs**, increase in matrix and hyalinosis
```
l **Global sclerosis of glomeruli**, **tubular atrophy** and
interstitial fibrosis (with disease progression)
```
2. sclerotic and nonsclerotic areas show diffuse
effacement of foot processes; focal detachment of
epithelial cells with denudation of GBM
3. IgM and C3 in the sclerotic areas and/or
mesangium
94
Focal Segmental Glomerulosclerosis
Collapsing glomerulopathy
l Retraction and/or
collapse of glomerular
tuft
l Proliferation and
hypertrophy of podocytes
l Tubular microcysts
l May be idiopathic but is
the most characteristic
lesion in HIV-AN
l Poor prognosis
95
Focal Segmental Glomerulosclerosis
Pathogenesis:
l\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_– **hallmark of FSGS due to
l Circulating cytokine**
l Genetically determined **defects affecting slit
diaphragm components**
**l Hyalinosis and sclerosis** – entrapment of plasma
proteins in extremely hyperpermeable foci and
increased ECM deposition
Epithelial damage
96
Focal Segmental Glomerulosclerosis
Pathogenesis:
l Genetic basis:\_\_\_\_\_\_\_\_\_\_\_- gene in chromosome
**19q13 encodes nephrin** – **component of slit
diaphragm** – control glomerular permeability
l Mutations of this gene give rise t**o congenital
nephrotic syndrome of the Finnish type,**
**producing minimal change disease-like
glomerulopathy**
NPHS1
97
Focal Segmental Glomerulosclerosis
Pathogenesis:
l **\_\_\_\_\_\_\_\_\_\_\_\_** gene in chromosome 1q25-q31 encodes
**podocin** – component of slit diaphragm
l Mutations in NPHS2 result in a syndrome of
**steroid-resistant nephrotic syndrome of
childhood onset**
l Podocin mutations may account for **30% of
cases of steroid-resistant NS in children**
**NPHS2**
98
Focal Segmental Glomerulosclerosis
Clinical Course:
l Little tendency for spontaneous remission in
idiopathic FSGS
l Variable responses to corticosteroid therapy
l Progression of renal failure occurs at variable
rates
l Recurrences are seen in 25 to 50% of patients
receiving allografts
99
Membranoproliferative
Glomerulonephritis
l Characterized by alterations in the GBM,
proliferation of glomerular cells and leukocyte
infiltration
l Mesangiocapillary GN
l May present only with hematuria or proteinuria in
the non-nephrotic range or combined nephroticnephritic
syndromes
l Primary (idiopathic) or secondary
l Primary MPGN: types I and II
