Renal Pathology Guide on Kidney Structure and Function

1
1
Renal Pathology
Dr.Dexter, MDFRCPath

Undercover Professor
Department of Pathology

St. Georges University School of
Medicine
2
Normal Kidney and investigations
for renal disease
Shivayogi Bhusnurmath, MD
Department of Pathology
3
Kidney
Glomeruli
Tubules
Interstitium
Blood vessels
Ureters
Urinary bladder
Urethra
Kidney and the urinary
collecting system
4
Compartments
Glomeruli
Tubules
Interstitium
Vasculature
5
Glomerular capillary
Fenestrated ECS
300 50 nm
Collagen IV (1-6)
Goodpasture Ag on NC1 domain of 3
collagen chain
Podocytes foot processes
6
Glomerular filtration
membrane
Fenestrated endothelial cells
Glomerular basement membrane (GBM)
Central lamina densa with lamina rara on either
side
Visceral epithelial cells
Interdigitating foot processes
Filtration slits (20-30 nm)
Filtration slit diaphragm
Mesangial cells and matrix
2
7
Laboratory assessment of
renal disease
8
Diagnostic work up for renal
problems
History
Physical examination
Urinalysis
Blood chemistry
CBC and peripheral smear
Radiology and imaging
Renal biopsy
9
Lab tests in renal disease
Glomerular Function
creatinine
blood urea nitrogen (BUN)
Urinalysis
physical
chemical
microscopic
10
Tests of glomerular function
Creatinine - muscle creatinine
degradation product
Blood urea nitrogen (BUN) - waste
product of protein metabolism
Clearance tests
11
creatinine & BUN = glomerular
filtration rate (GFR)
prerenal: volume loss, effective
volume, and fluid sequestration,
postrenal: obstruction
intrinsic renal disease: glomerular, tubular,
vascular, interstitial diseases
12
BUN in decreased renal function
BUN liver disease, celiac disease,
SIADH
3
13
Clearance tests
Amount of plasma cleared of a particular
substance in one minute
Better estimate of renal function
Creatinine clearance
14
Urinalysis
Urine analysis helps to define the
specific process affecting the kidneys.
Assessment includes:
physical - color, specific gravity, turbidity
chemical - pH, numerous molecules
microscopic - cells, crystals, casts
15
Urinalysis- physical
assessment
Color normal: yellow to amber and
clear
cloudy
cells
bacteria
16
Urinalysis- volume
Normal
750 ml - 2.5L/24 hours = 25-30 ml/hr
Abnormal
polyuria = urine output
oliguria = urine output
anuria = no urine output
17
Urinalysis- specific gravity
SG reflects the kidneys ability to concentrate
or dilute urine relative to the plasma.
Normal = 1.010 - 1.025
Increased = concentrated
dehydration - diarrhea, vomiting, sweating
SIADH
blood flow to the kidneys
glycosuria or proteinuria
18
Urinalysis-specific gravity
Decreased = dilute
diabetes insipidus ( ADH)
glomerulonephritis
pyelonephritis
renal failure (1.007-1.010)
low and fixed in End stage renal
disease
4
19
Chemical analysis
20
Microscopy
Crystals
Cells
Casts
21
Cells in urine
RBCs
Crenated/fragmented- ?
glomerular
Bacteria
22
Casts in urine
Casts are formed in the distal
convoluted tubule and
collecting ducts.
Finding indicates disease of
nephron and not lower down
23
Casts
Hyaline casts
may be normal
Red cell casts
glomerular or tubule injury
White cell casts
pyelonephritis
glomerulonephritis
24
Casts
Fatty casts
nephrotic syndrome
Granular
ATN
5
25
Radiological investigations
Plain X-Ray
Ultra sound
CT scan
Intravenous pyelography ( IVP)
Cystogram
Micturating cystogram
26
Clinical investigations
Cystoscopy
Fine needle aspiration
Needle biopsy
Nephrectomy
27
Renal biopsy
Needle biopsy- true cut, gun
Light microscopy
Immunofluorescence
Electron microscopy
28
Clinical manifestations of renal
disease and pathogenesis of
glomerular injury

29 30
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Basic functions of the kidney
Excretion of waste products
Regulation of salt and water balance
Regulation of acid base balance
Regulation of blood pressure
Secretion of certain hormones
Tremendous reserve capacity
32
Clinical manifestations of urinary
system
SYMPTOMS
Edema
Headache
Hematuria
Oliguria
Frequency
Urgency
Hesitancy
Painful urination
Flank pain
Mass
SIGNS
Azotemia
Uremia
Hematuria
Proteinuria
Hypertension
Hypoalbuminemia
Edema
Hyperlipidemia
Lipiduria
Bacteruria
Pyuria
Mass
33
Major clinical syndromes of
urinary system
Acute renal failure
Chronic renal failure
End stage renal disease
Nephritic syndrome
Nephrotic syndrome
Asymptomatic proteinuria
Asymptomatic hematuria
Urinary tract obstruction
Urinary tract infection
Nephrolithiasis
Mass lesion ( tumors)
34
Renal syndromes
Acute renal failure (days to a few weeks)
sudden onset of azotemia with oliguria or anuria
Chronic renal failure (CRF) - Azotemia
progressing to uremia over several months
(3 months) or years
failure to concentrate urine-
End stage renal disease - less than 10%
function-(fixed SG 1010) usually follows CRF
35
Major clinical syndromes of
urinary system
ARF - Acute glomerulonephritis
Acute tubular necrosis
Acute interstitial nehpritis
Malignant hypertension
CRF - Chronic glomerulonephritis
Chronic interstitial nephritis
Benign hypertension
36
Acute nephritic syndrome
acute onset
hematuria
mild to moderate proteinuria
HTN
7
37
Nephrotic syndrome
heavy proteinuria (> 3.5 gms/day)
hypoalbuminemia
edema
hyperlipidemia
lipiduria
38
Nephritic Nephrotic
Syndrome Syndrome
Proteinuria +
Edema +
Hyperlipidemia +
Hematuria +++
RBC casts ++
Hypertension ++
+++
+++
+++
+/-
-
+/-
39
Asymptomatic hematuria - microscopic
Asymptomatic proteinuria - dip stick (+)
Rental tubule defects
polyuria, nocturia, and electrolyte disorders
40
Urinary tract infection (UTI)
bacteria and pyuria
Nephrolithiasis
renal colic, hematuria, recurrent stone
formation
41
Mass lesions
Tumors
Hydronephrosis
Polycystic kidney
42
Systemic manifestations of renal
disease
Systemic effects of renal failure and uremia
involve
fluid and electrolyte control
calcium and phosphate metabolism
hematologic
cardiopulmonary
gastrointestinal
Neuromuscular
skin
8
43
Fluid and electrolyte manifestations
dehydration
edema
hyperkalemia ( K)
metabolic acidosis
44
Calcium and phosphate metabolism
hyperphosphatemia ( PO
4
)
hypocalcemia ( Ca)
secondary hyperparathyroidism ( PTH)
renal osteodystrophy
45
Hematologic manifestations
anemia
bleeding diathesis
46
Cardiopulmonary manifestations
Hypertension
Congestive heart failure
pulmonary edema
uremic pericarditis
47
GI manifestations
nausea and vomiting
bleeding
esophagitis, gastritis, colitis
48
Neuromuscular manifestations
myopathy
peripheral neuropathy
encephalopathy
9
49
Dermatologic manifestations
sallow color
pruritis (itching)
dermatitis
50
Renal failure
Azotemia = BUN and creatinine
prerenal - perfusion
renal - kidney disease
postrenal - obstruction
Uremia = azotemia + clinical signs and
symptoms
51
Sites of renal damage
Glomerular
Tubular- Interstitial
Vascular
Irrespective of the site of primary
damage- eventually all the three
components get damaged- sclerosed
glomeruli, atrophied tubules, scarred
interstitium and hyalinized vessels
52
Glomerular damage
Primary
The kidney is the predominant organ
involved in the disease process.
Secondary
Systemic disease process that secondarily
involves the kidney.
Consequences
Loss of selective barrier function
Decreased GFR
53
Pathogenesis of glomerular
disease
Circulating immune complexes
Anti-GBM = immune complexes
formed at the site
Cell mediated immune response-
cytokines
54
Complement- leukocyte mechanism
Complement only mechanism
C5-C9 Lytic component
Cytotoxic antibody mechanism
Monocytes and macropahges
Infiltrate damaged areas and release
biologically active molecules
Platelets
Release prostaglandins and PDGF
Fibrin related products - (PMN Infiltration
and cell proliferation)
Cytokines
Mediators of injury
10
55
Consequences of glomerular
injury
Manifestations
GFR
proteinuria
Ablation glomerulonephropathy
When some glomeruli are damaged, it puts
additional load on surviving glomeruli. They are
hyperperfused leading to further damage to more
glomeruli.Vicious progressive cycle of scarring of
glomeruli even if the original inciting agent is
removed.
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Glomerulonephritis

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Classification of glomerular
disease
Clinical syndromes
Morphological
Etiological
Primary
Secondary ( systemic diseases )
Hereditary
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Clinical classification-
glomerular diseases
Nephritic syndrome
Nephrotic syndrome
Mixed nephritic- nephrotic
Incidental hematuria
Incidental proteinuria
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Morphological classification-
glomerular diseases
Proliferative GN:
Acute diffuse proliferative GN
Rapidly proliferative GN
Membranoproliferative GN
Focal proliferative GN
Nonproliferative GN:
Minimal change disease
Membranous GN
Focal segmental Glomerulosclerosis
Mixed patterns
Chronic GN
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Chronic GN
End point of many progressive GN
FSGS, IgA nephropathy, MGN, MPGN
30-50% of all end stage renal disease due to CGN
Often impossible to determine the original lesion
20% may have no prior history of renal disease
Others have episodes of nephritic / nephrotic
illness
Proteinuria gets reduced because glomeruli get
obliterated
ESRD- <10% function, low fixed SG of urine
62
Morphology
Symmetrically contracted kidneys
Diffusely granular surface
Advanced scarring of glomeruli and Bowmans
space
End stage kidneys
Hyalinization of glomeruli
Marked interstitial fibrosis
Tubular atrophy
Sclerosis of arteries and arterioles
Lymphocytic infiltrates
Chronic GN
63
Relationships
MPGN
IG-A
FSG
MCD
MGN
APGN
RPGN
Nephrotic syndrome Nephritic syndrome
Chronic GN
64
Nephritic syndrome - clinical
Acute onset
Oliguria, hematuria
Edema (periorbital)
Red cell casts
azotemia
Hypertension
Mild proteinuria
65
Acute poststreptococcal
glomerulonephritis
Usually 6-10 year olds, can affect
adults
History of nausea, fever, malaise
History of pharyngeal or skin strep
infection, 1-4 weeks prior
could follow other infections
66
Nephritic syndrome-
pathogenesis
Inflammation
Capillary wall
damage
RBC
extravasation
Hemodynamic
changes
GFR
Fluid + Renin
retention release
Hypertension
12
67
glomerulonephritis
Group A -hemolytic streptococcus
90% of cases are types 12, 4, 1 or 49
Immune complex mediated
antibodies to streptococcal antigen
complement and immune complexes
deposited in the glomeruli
68
glomerulonephritis
Hypercellular glomeruli due to:
proliferation of endothelial cells
and mesangial cells
PMNs and macrophages
Tubules with red cell casts
Light microscopy
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glomerulonephritis
IF: granular deposits of IgM, IgG, and C3
along GBM and mesangium
EM: scattered subepithelial
electron dense deposits like humps
70
glomerulonephritis
Presentation
Hypertension, edema and BUN
Labs
ASO titers, C3,
Outcome
children - 95% recover with conservative
treatment ( no need for biopsy)
adults 60% recover spontaneously
71
Outcome
Sometimes
Clinical presentation of acute nephritic
illness but severe and downhill course
Called - Rapidly progressive GN (RPGN)
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Rapidly progressive
glomerulonephritis
Rapid decline in renal function
(anuria and uremia) leading to
ESRD (90%)
Characterized by crescent
formation
proliferation of parietal epithelial cell
infiltration of monocytes macrophage
fibrin deposition
13
73
Rapidly progressive
glomerulonephritis
Type I - idiopathic
Anti- GBM disease / Goodpastures
Syndrome
Type II - immune complex mediated
Postinfectious eg. PSGN
SLE
IgA nephropathy
74
Rapidly progressive
glomerulonephritis
Type III - pauci-immune
no anti-GBM or immune complexes
Most have serum ANCA positivity
Wegners granulomatosis (c- ANCA)
Microscopic polyarteritis (p-ANCA)
75
Good Pastures syndrome
Pulmonary and renal symptoms
hemoptysis and pulmonary hemorrhage
hematuria and RBC casts
proteinuria and edema
Hypertension
Rapid decline in renal function in days
and weeks- End stage renal disease
M:F = 3:1, usually in the 3rd decade
Treatment: plasmapheresis, steroids,
cytotoxic drugs
76
Crescents in most of glomeruli
Focal segmental fibrinoid necrosis
Casts
Light microscopy
77
IF: diffuse linear
deposition of IgG and C3
in the GBM and
pulmonary alveolar BM
EM: no deposits
disrupted GBM
78
Wegners granulomatosis
Renal pathology
20% with renal disease at the time of
presentation
80% involvement of the kidneys over
time
Renal insufficiency, proteinuria,
hematuria
14
79
Focal segmental necrotizing
glomerulosclerosis and
crescents
Pauci immune- no immune
complexes on IF, EM
Small and medium arteritis
Granulomatous inflammation -
rare
80
Wegners granulomatosis-
pathogenesis
Environmental injury with increased
macrophage IL-12 and TH1 cytokine
profile
Development of pathogenic ANCA
81
Wegners granulomatosis- ANCA
Anti-neutrophilic antibody (ANCA)
>90% sensitivity and specificity
Antibody titers
decline after therapy
increase before a relapse
Two patterns
C-ANCA = anti-serine protease- more specific for
Wegners
P-ANCA = anti-myeloperoxidase- nonspecific-
seen in other vasculitides like polyarteritis
82
83
Glomerulonephritis-
Nephrotic syndrome
84
Nephrotic syndrome
Massive proteinuria - > 3.5g/day
Edema (anasarca)
Hypoalbuminemia (<3g/dl)
Hyperlipidemia
Lipiduria free fat, fatty casts, or oval
fat bodies in the urine
15
85
Proteinuria
< 100-150 mg/day - normal
Up to 300 mg/day - microalbuminuria
>1- 2 g/day - frequently the result of glomerular
disease
>3.5 g/day - nephrotic range
Selective - albuminuria only
Non selective -all proteins (usually more
severe glomerular injury)
86
Nephrotic syndrome
Minimal change disease (MCD)
Membranous glomerulonephritis (MGN)
Focal segmental glomerulosclerosis
(FSG)
Membranoproliferative
glomerulonephritis (MPGN)
Diabetic glomerulosclerosis
Amyloidosis
87
Minimal change disease (MCD)
Primary cause of nephrotic syndrome in
children (peak 2-6 y/o)
No HTN or hematuria
No azotemia
Proteinuria selective for albumin
Rapid response to steroids in children
Immunologic basis- no immune complexes
demo. ? T cell mediated cytokine induced
damage to foot processes
88
LM: Normal
IF: Normal
EM: uniform and diffuse broadening
of the foot processes
89
Lipoid nephrosis
Earlier days- in untreated minimal
change disease
Large amounts of lipid coming out of
leaking glomeruli picked up by lining
epithelial cells of PCT
Cells appeared large foamy and
vacuolated
Gave large pale appearance to kidneys
Was termed as lipoid nephrosis
90
60-80% develop complete remission
following steroid treatment (steroid
sensitive)- do not need a biopsy
Some patients relapse if steroid treatment is
stopped (steroid dependent)
Some patients may be or become steroid
resistant
Only patients who eventually turn out to have
FSGS progress
16
91
Membranous glomerulonephritis
(MGN)
Most frequent cause of nephrotic syndrome in
non-diabetic elderly 40% of adults
Nonselective proteinuria
Rarely- hypertension and hematuria
85% idiopathic (autoimmune)
15% secondary: SLE; IDDM; carcinomas;
hepatitis B & C; syphilis; Rx: Au, penicillamine
and NSAIDs
92
Caused by the subepithelial accumulation of
immune complexes
circulating Ab-Ag complex
? Ag, tumor Ag, or Hepatitis B & C Ag
Anti-glomerular autoantigen complex
HLA susceptibility
C5b-C9 mediated
93
LM: Diffuse thickening of glomerular
capillary loops.
IF: Granular deposits along glomerular
capillary loops (IgG, C3).
EM: Subepithelial electron dense
deposits along glomerular capillary
basement membrane.
94
Thickening of GBM due to irregular
dense deposits. The GBM between
them appears as spikes
IF: diffuse/granular IgG and C3
GBM staining
Light and IF Microscopy
95
Electron dense deposits between
the GBM and the overlying epithelial
cells
Electron Microscopy
96
30 - 40% of cases may show
spontaneous remission.
Progression is very slow.
Approximately 20% of patients develop
ESRD (proteinuria drops because of
glomerulosclerosis)
Secondary cases can be cured if
etiologic factor can be eliminated.
17
97
Focal segmental
glomerulosclerosis- FSG
Nephrotic syndrome in children and adults
Black race is a predisposing factor
Presentation - nonselective proteinuria (
nephrotic range )
Associated with hematuria and
hypertension
Poor response to steroids
50% progress to ESRD in 10 yrs
20% rapid progression in 2 yrs
Recurrence in grafts
98
Focal glomerulosclerosis- FSG
Primary - idiopathic
Secondary
HIV, heroin, sickle cell disease, massive
obesity
Superimposed upon other GN like IgA
nephropathy
Renal ablation glomerulopathy
Genetic- nephrin, podocyn molecules
HIV linked- can involve entire tuft- (global)-
collapsing glomerulopathy- proliferation of
visceral epithelial cells also seen
99
Focal segmental
glomerulosclerosis- FSG
Varying numbers of glomeruli (focal) are
affected - juxtamedullary first-
segmental collapse of the GBM with
mesangial matrix & hyaline masses
sclerosis.
Light Microscopy
100
Nonsclerotic areas show diffuse loss of
foot processes and broadening
Pronounced focal detachment of the
epithelial cells
Electron Microscopy
101
Affects juxta medullary glomeruli
first
Because of their deep location and
the patchy nature of the disease
process, the renal biopsy may fail
to pick up diseased glomeruli
Misdiagnosed as minimal change
disease
102
Mixed Nephritic- Nephrotic
Significant proteinuria with
hematuria and hypertension
glomerulonephritis (MPGN)
FSG
IgA nephropathy
18
103
Membrano proliferative
glomerulonephritis- MPGN
5-10% of idiopathic nephrotic
syndrome
Older children and young adults
Presentation
hematuria
proteinuria
Progressive course - 50% CRF in 10
years
104
Primary MPGN - idiopathic
immune complex mediated - activation of
complement, Source of antigen unknown
Secondary MPGN
chronic immune complex disorders (SLE)
malignancies (e.g. CLL)
hereditary deficiency of complement
regulation
105
Type 1
2/3 cases
immune complexes and C activation via
both alternate and classical pathways
106
Lobular appearance
Hypercellular glomeruli due to
mesangial cell proliferation
mesangial matrix
GBM thickening on HE, split
appearance on PAS and silver
stains - tram track
Light Microscopy
107
glomerulonephritis- MPGN-type1
Electron Microscopy
double-contour basement
membrane
subendothelial electron dense
deposits
108
Type 2 dense deposit disease
1/3 cases
activation of the alternate complement
pathway
serum C3
normal C1 and C4
C3 nephritic factor (autoantibody to C3
convertase)
19
109
glomerulonephritis- MPGN-type2
IF: granular C3 within the GBM, no IgG
EM: irregular ribbon-like electron dense
deposits within the lamina densa
110
Diabetic nephropathy
Diabetes #1 cause of ESRD in the US.
Progressive disease
microalbuminemia - initial presentation
nephrotic proteinuria - 12 - 22 yr period
ESRD within 5 years of diagnosis of
nephrotic syndrome
Hypertension is common
Treatment - good control of diabetes
111
Diabetic nephropathy
Glomerulosclerosis
Pyelonephritis
Hypertension
Papillary necrosis
Tubular epithelial vacuolation- seen in
the pre-insulin era due to glycogen
accumulation
112
LM - Early:
-Large glomeruli
- Later:
-Diffuse mesangial widening-cells
and matrix
-Nodular mesangial sclerosis
(Kimmelstiel-Wilson nodules)
-Glomerular capillary basement
membrane thickening
IF - Nonspecific
EM - GBM thickening and mesangial
matrix increase
113
IF: negative
EM: thickened glomerular capillary
basement membranes and
increased mesangial matrix
114
Amyloidosis
Kidney most common sight for amyloid
deposition.
Presentation
proteinuria to nephrotic syndrome
infrequent hematuria or hypertension
results in renal failure
20
115
Amyloidosis
Eosinophilic (pink) nodular
deposits in the mesangium,
GBM, tubular basement
membrane, arterioles
116
117
Other Glomerulopathies
118
Miscellaneous
Ig A nephropathy
Alport syndrome
SLE nephropathy
119
IgA nephropathy
Bergers disease
Most common glomerulonephritis worldwide
Any age, peak 15-30 years, M > F
Asia > U.S., rare among Blacks
Presentation
recurrent hematuria - gross (40%) or microscopic
(40%)
often follows a mucosal infection (IgA in mucosa)
nephrotic syndrome (10%)
renal failure (10%)
120
IgA nephropathy
Slowly progressive - CRF in 50% of
cases over a 20 year period
Markers for poor outcome:
hypertension, crescents, glomerular
sclerosis, interstitial fibrosis, heavy
proteinuria
May recur in up to 60% of
transplanted kidneys
21
121
IgA nephropathy
IgA containing immune complexes in the
mesangium
serum polymeric IgA
circulating IgA complexes
Unknown antigen
GI or respiratory tracts infections can
induce recurrence
Celiac disease, liver disease (IgA
metabolized in the liver)
122
IgA nephropathy
Histology- variable
Increase in mesangial cells and
matrix- most common
Can mimic any type of GN
morphologically
123
IgA nephropathy
Mesangial widening
cellularity & mesangial
matrix
Segmental proliferation
124
IgA nephropathy
Mesangial
deposition of IgA
and C3
Dense deposits in
the mesangium
IF and EM
125
Alports syndrome
Hereditary glomerulonephritis
X-linked disorder, autosomal dominant
and recessive forms as well
mutations in COL4A5 (5) gene for type
IV collagen
126
Alports syndrome
Combination of nephritis, nerve deafness,
eye disorders, disorders of the skin,
platelets
M>F in frequency and severity
Present at age 5 - 20, CRF by age 20 - 50
Hematuria - gross or microscopic
Progresses to nephrotic syndrome and
ERSD
Treatment: dialysis and renal transplant
22
127
Alports syndrome
Nonspecific -
segmental or global
glomerulosclerosis
Nonspecific - foamy
macrophages
Light microscopy
128
Alports syndrome
IF: negative
EM: thickening and attenuation of the
GBM, with splitting of the lamina
densa
IF and EM
129
Glomerular involvement in systemic
diseases
130
Lupus nephritis
60-70% of patients have abnormalities
in the glomeruli on light microscopy
>95% of patients have abnormalities on
IF and EM
IF generally shows abundant IgG, IgA,
IgM, and C3
EM generally shows subepithelial,
subendothelial, and mesangial deposits
131
Lupus nephritis
Patterns of glomerular disease (WHO)
normal
mesangial
focal proliferative
diffuse proliferative
membranous
combinations
(wireloop lesions- irregular thickeming of
basement membrane like twisted wire- due to
irregual dense immune complex deposits,
hematoxyphil bodies- small dense bluish bodies
representing denatured nuclear material),
necrosis, thrombi,crescents
Intersitial lesions
Vascular lesions
132
Focal proliferative
glomerulonephritis
Can be a renal manifestation of systemic illness
like SLE or Infective endocarditis or Ig A
nephropathy
Should not be mistaken for FSGS
23
133 134
Tubular and interstitial
diseases
135
Tubular and interstitial
diseases
Tubulointerstitial nephritis
Acute tubular necrosis (ATN)
136
Tubulointerstitial nephritis
Acute pyelonephritis
Chronic pyelonephritis
Acute drug induced interstitial nephritis
Chronic analgesic abuse nephropathy
137
Acute onset
pain - costovertebral
fever (>39.4 C, 103 F) shaking chills,
C/O dysuria and urgency
138
Lab findings
WBC
pyuria with WBC casts
hematuria - acute phase
(+) urine cultures
24
139
Complications
papillary necrosis
perinephric abscesses
pyonephrosis
140
Ascending
E. coli - causes 80%
ureteric reflux
instrumentation
obstruction
pregnancy (10%with bacteruria)
141
Hematogenous (bacteremia)
E. coli and Staph.
preexisting renal lesion
diabetes
immunosuppression
Microabscesses
142
Gross appearance:
Surface - areas
of microabscess
Hyperemia
Hydronephrosis(+-)
143
Microscopic features:
Patchy acute
inflammation
Progresses
throughout tubules
144
Insidious - symptoms only after it is
well advanced
ESRD - frequency, fatigue, nausea
Hypertension
History of:
recurrent acute UTIs
urinary tract abnormalities (e.g. reflux
and/or obstruction)
25
145
Gross features:
Broad coarse scars (poles)
Distorted medulla and
calyces
146
Thyroidization
dilated atrophic tubules
eosinophilic casts
chronic inflammation
147
Glomerular
sclerosis
hyalinosis
capsular thickening
necrosis
148
Interstitial changes:
plasma cells
lymphocytes
fibrosis
149
Drug induced interstitial
nephritis
Clinical presentation includes:
fever
skin rash
Labs
hematuria
mild proteinuria
WBC casts
eosinophilia
150
nephritis
Signs and symptoms follow 2 - 40 days
after Rx
cephalosporins
thiazides
NSAIDS (phenylbutazone)
cimetidine
Type IV hypersensitivity
26
151
nephritis
Microscopic features:
interstitial chronic inflammation
lymphocytes
macrophages
eosinophils
granulomas (+/-)
152
Analgesic nephropathy
Chronic use, and >2kg, of phenacetin
with aspirin, acetaminophen, or
caffeine
F>M 3-5:1, age - 50s
up to 5% progress to ESRD
153
Analgesic nephropathy
Papillary necrosis
occurs first
various stages of damage
Chronic tubulointerstitial nephritis
secondary event
154
Acute tubular necrosis
Most common cause of ARF
Usually follows shock
Three stages
Initiating stage
Maintenance stage
Recovery stage
155
Acute tubular necrosis- initial phase
36 hrs
inciting process
ischemia or toxin
exposure
+/- renal function
156
Acute tubular necrosis-
maintenance phase
Oliguria with ischemia and non-oliguric
ATN with nephrotoxins
salt and water overload
BUN
serum K+
Metabolic acidosis and uremia
Requires supportive therapy
27
157
Acute tubular necrosis- recovery
phase
Polyuria
Hypokalemia
creatinine
158
Benign nephrosclerosis
Renal atrophy
Kidney surface has an even, fine, granularity
and the cortex is thinned.
Gross appearance:
159
Medial and intimal thickening in response to
hemodynamic changes.
Hyaline deposition following endothelial cell
injury.
Ischemia results
160
tubular atrophy
interstitial fibrosis
glomerular sclerosis
intimal & medial thickening
161
Luminal narrowing due to:
Intimal and medial thickening
Hyaline deposited in arteriole walls
Leads to ischemia
162
1-5% of HTN patients - malignant
hypertension
Superimposed on other forms of
hypertension
Syndrome
diastolic pressures > 130 mm Hg (e.g. 300/150)
papilledema
encephalopathy
cardiovascular abnormalities
renal failure
28
163
Pure form
Younger adults
M > F
African American
50% 5 year survival
164
Flea-bitten appearance - pinpoint
petechial hemorrhages on the cortical
surfaces.
165
Endothelial injury leads to fibrin escape
(fibrinoid necrosis of arterioles)
PDGF from activated platelets induces
smooth muscle hyperplasia (hyperplastic
arteriolitis or "onion skinning.)
166
Thrombotic microangiopathies
Clinical characteristics include:
microangiopathic hemolytic anemia,
thrombocytopenia
acute renal failure
Childhood hemolytic-uremic syndrome
Adult hemolytic-uremic syndrome
Thrombotic thrombocytopenic purpura
167
Hemolytic uremic syndrome-
HUS
Clinical features
Flu-like prodome
Sudden onset of:
Bleeding hematemesis and melena
Severe oliguria and hematuria
50% with HTN
168
HUS
Clinical features:
Microangiopathic hemolytic anemia.
dialysis leads to recovery
25% develop CRF
29
169
HUS - etiology
Endothelial injury - Shiga-like bacterial
endotoxins, cytokines, viruses or anti-EC
Abs
Infections - E. coli (O157:H7) and viral
Complication of pregnancy
Secondary HUS - scleroderma, SLE,
malignant hypertension, chemotherapy, or
immunosuppressive drugs.
Hereditary
170
HUS
Petechial hemorrhages
Cortical necrosis
171
HUS
Vascular thrombosis
Subendothelial widening in an arteriole
Fibrinoid necrosis
Fibrin deposition
Intimal proliferation
Subendothelial space expansion
172
Renal artery stenosis
Unilateral
Presents clinically as hypertension
Fibromuscular dysplasia
Cause not known
Surgical excision resolves
173
Vasculitis
Any systemic vasculitis can also
involve the kidney
Polyarteritis nodosa
Microscopic polyarteritis
174
Atheroembolism
Scattered infarcts with coagulative
necrosis- small depressed scars on the
cortex
Cholesterol clefts within accurate and
intralobular arteries
30
175
Atheroembolism
The clinical impact is usually minimal
and depends on pre-existing renal
function.
Associated with:
severe atherosclerosis
abdominal surgery on atherosclerotic
aneurysms
aortography or intra-aortic canulization
176
177
Urinary tract obstruction

178
Causes
Pelvis- calculi, tumor, Ureteropelvic
junction (UPJ) stricture
Ureter- Calculi, pregnancy, tumor
Bladder- Calculi, tumor, neurogenic
Prostate- Benign hyperplasia
Urethra- stricture
179
Urolithiasis
Common urologic disorder -
10% US population
Calculi - rocklike particles
that vary from a grain of sand
to golf ball in size
180
Urolithiasis- Clinical features
M > F - 3-4:1
Hereditary in many cases
20 - 50 yrs age group
500,000 cases/year
$2,000,000,000 cost/year
31
181
May be asymptomatic - usually when in
the kidney
Renal colic - abrupt onset
when the stone is in the ureter
intense pain - urine back flow pressure on
the kidney
flank pain - lower abdomen - groin
182
Nausea, vomiting due to severe renal
colic
Hematuria - 95% cases - gross or
microscopic
Ureter blockage
hydronephrosis
recurrent pyelonephritis
183
Urolithiasis- Etiology
Increased urine concentration leads
to super saturation due to:
Excessive mineral excretion
calcium - 75% of stones (oxalate/PO4)
Stuvite (Mg
2
NH
4
PO
4
) (10-15%) -
infections
uric acid (5-10%)
cystine (rare)
2) Dehydration - low fluid volume
184
Urolithiasis- Treatment
Drink fluids - prevention
Extracorporeal shock wave lithotripsy
(ESWL)
Dietary changes based on stone
analysis
calcium supplements
oxalate (excess - meat, chocolate, tea)
185
Urolithiasis- Pathology
unilateral 80% of cases
branching stones - Staghorn
calculus
186
Hydronephrosis
The clinical implications vary:
bilateral vs. unilateral hydronephrosis
complete vs. incomplete obstruction
Unilateral
obstruction at or above the ureters
often clinically silent due to compensatory
action of contralateral unaffected kidney
32
187
Hydronephrosis
Unilateral hydronephrosis
obstruction at or above the ureters
Bilateral hydronephrosis
obstruction below the ureters
188
Hydronephrosis
Incomplete obstruction may lead to:
polyuria, nocturia - renal concentration
calculi and interstitial nephritis
Hypertension is common
permanent renal damage in 3 months
Complete obstruction
anuria
permanent renal damage in 3 weeks
189
Hydronephrosis
Dilated renal pelvis / calyces
Tubular atrophy, interstitial
fibrosis, chronic inflammation
190
191
Cystic renal diseases
Shivayogi Bhusnurmath, MD
Department of pathology
St. Georges university
192
Renal cysts
Adult Polycystic Kidney Disease
Childhood Polycystic Kidney Disease
Medullary Sponge Kidney
Dialysis Acquired Cysts
Simple Cysts
33
193
Renal cysts
Hereditary, developmental and
acquired disorders.
Cystic distortion
Confused with renal cancer
194
Adult polycystic kidney
usually asymptomatic
30 - 40 years
mass
proteinuria
hypertension
rupture flank pain & hematuria
10% of CRF>50 y/o
Clinical Presentation (insidious)
195
Incidence - 1/400 - 1/1000
Etiology
autosomal dominant
mutations involving PKD1 (90%), PDK2
(10%) and PKD3 genes
196
polycystic liver disease (40%)
cysts- lungs, spleen & pancreas
(rare)
Berry aneurysms in Circle of Willis
(10%)
mitral valve prolapse (20-25%)
Other Congenital Anomalies
197
Bilateral
Variable size cysts in cortex and medulla
Clear - yellow fluid
Lined by atrophic epithelial lining
Parenchymal atrophy
Morphologic Findings
198
Childhood Polycystic Kidney
Autosomal recessive
Dilated collecting ducts
Associations-
Polycystic liver
Hepatic fibrosis
Death in infancy or childhood
34
199
Medullary sponge kidney
5 mm cysts in the renal papillae
connect with collecting ducts
Often incidental
Associated with
UTIs
hematuria
calculi (medullary nephrocalcinois)
200
Dialysis acquired cysts
Patients with ESRD & prolonged
dialysis
cortical and medullary cysts
tubule obstruction
often asymptomatic
hematuria
renal cell ca (7%)
201
Simple renal cysts
Single - multiple cortical cysts
Incidental
hematuria
202
203
Renal tumors
204
Renal tumors
Renal Cell Carcinoma (RCC)
hypernephroma / adenocarcinoma
Wilms Tumor (Nephroblastoma)
Transitional Cell Carcinoma (TCC)
35
205
Renal cell carcinoma
Most common renal tumor (85-90%)
3% of all adult malignancies
Age - 50-70 years
M:F - 3:1
206
Renal cell carcinoma-
etiology
Tobacco use - men > women
Chronic dialysis for CRF (3-6x risk)
Drugs/chemicals phenacetin
Genetic - 5% inherited
207
Von Hippel-Lindau Syndrome
Autosomal dominant
Unbalanced translocation (t3;6, 3;8, 3;11) VHL gene
3p25-26
Several tumor types
multiple RCC
hemangioblastomas CNS and eye
pheochromocytomas
208
Renal cell carcinoma- clinical
Hematuria (60%) - often painless
Hematuria (60%) - often painless
Costovertebral (flank) pain (40%)
Palpable abdominal mass (40%)
Fever, weight loss, anemia
Paraneoplastic syndromes
Associated with metastatic disease
lungs (50%), bone (33%)
209
Renal cell carcinoma- clinical
Paraneoplastic Syndromes
common
polycythemia - erythropoietin
hypercalcemia - PTH-like protein
hypertension - renin
hyponatremia - ADH
Cushings syndrome - ACTH
210
3-15 cm mass in the renal poles
Yellow with areas of hemorrhage
and necrosis.
Sharp margins
Tendency to invade the renal vein
36
211
Clear cell
Granular (eosinophilic)
Sarcomatoid
Papillary
212
Renal cell carcinoma- prognosis
Overall 5 year survival is 45%
Treatment
nephrectomy (stages I and II)
radiation and chemotherapy
213
Renal cell carcinoma-
inherited
Bilateral
Multifocal
Appear at a younger age than
sporadic RCC
214
Wilms tumor- nephroblastoma
Most common renal tumor in children -
450 new cases/year
Mutations of WT-1 or WT-2 tumor
suppressor genes
2 - 5 years old at time of presentation
palpable mass, abdominal pain and/or
hematuria
90% 5 year survival with therapy
215
Wilms tumor
Tan lobulated mass that replaces
much of the kidney
216
Wilms tumor
Three components:
stromal - spindle cells and muscle
epithelial tubules
blastemal - small immature cells with a
high N/C ratio
Varying degrees of differentiation- related
to prognosis and subtypes
37
217
Transitional carcinoma- renal
pelvis
5-10% renal tumors
50% have urinary bladder TCC
Etiology - similar to TCC of the bladder
Presentation - painless, gross hematuria
Derived from urothelium

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