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Renal
Pathology
MD4 Block
III.
Renal Pathology Outline
• Introduction
• Glomerular diseases
• Tubular and interstitial diseases
• Diseases involving blood vessels
• Cystic diseases
• Tumors
Renal Pathology Outline
• Introduction
Introduction
• Functions of the kidney:
– excretion of waste products
– regulation of water/salt
– maintenance of acid/base
balance
– secretion of hormones
• Diseases of the kidney
–
–
–
–
glomeruli
tubules
interstitium
vessels
Introduction
• Azotemia:  BUN, creatinine
• Uremia: azotemia + clinical disease
-Pericarditis ,Skin lesions, Gastro intestinal symptoms,
Peripheral neuropathy
• Acute renal failure: oliguria(urine output between 300500mls/day
• Chronic renal failure: prolonged uremia
Introduction
Nephrotic syndrome
• Massive
proteinuria>3.5gm/day
• Hypoalbuminemia
Nephritic syndrome
• Proteinuria<3.5gm/day
•Hematuria
• Oliguria
• Edema
• Hyperlipidemia/-uria
• Azotemia
• Hypertension
Renal Pathology Outline
• Introduction
• Glomerular diseases
Normal glomerulus
Nephrin
Nephrin molecules
extend towards each
other from neighbouring
foot processes
Within the cytoplasm of
the foot processes,It
forms molecular
connections.
Mutations in genes
encoding these proteins
gives rise to nephrotic
syndrome.
Characteristics of Glomerular Filtration
• Glomerular filtration allows for highly permeable
molecules i.e. water and small solutes to pass through.
This is known as glomerular barrier function
• The barrier is completely impermeable to solutes, which
are close to the molecular size and molecular charge of
albumin
• Cationic (positive) charged molecules are more
permeable
• Podocytes contain the slit diaphragm which maintains
the integrity by providing a diffusion barrier to the
filtration of proteins
Glomerular Diseases
Can be divided into :
1. Primary Glomerular Diseases
• Nephrotic syndrome
• Nephritic
• Idiopathic RPGN
2. Secondary Glomerular diseases
• Nephrotic
• Nephritic
• RPGN
3. Hereditary disorders
4.Chronic GN.
Primary Glomerular Disease
Nephrotic
• Minimal change disease (MCD)
• Focal and segmental glomerulosclerosis
• Membranous nephropathy
• Membrano-proliferative
Nephritic
• Acute postinfectious GN
• Membranoproliferative GN
• IgA nephropathy
• Idiopathic RPGN or CrGN
• Focal segmental glomerulosclerosis
Secondary glomerular disease
Nephrotic:
• D/M Nephropathy
• Focal segmental
glomerulosclerosis
• Amyloidosis
• Drugs
Nephritic
• Lupus nepritis- (SLE)
• Diabetic nephropathy
• Goodpasture syndrome
• Microscopic polyangiitis
• Wegener’s
granulomatosis
• Henoch-Schonlein
purpura
• Bacterial endocarditis
related GN
• Thrombotic
• RPGN• FSGS
Hereditary Disorders
• Alport syndrome
• Fabry disease
• Podocyte/slit –diaphragm protein mutations
Pathogenesis of Glomerular Disease
Three mechanisms:
• Immunological
• Podocyte injury
• Nephron loss
Immunological:
• Most forms of glomerulonephritis (GN) result
from immunologic mechanisms .Three
mechanisms of immunological damage:
1) circulating immune complexes ( type III
hypersensitivity)
2) in situ immune complexes
3) cell mediated immune reaction (
hypothetical mainly)
Circulating Immune Complexes
• These are Type III hypersensitivity reactions
• Endogenous ( associated with SLE) or exogenous
(bacterial, viral, parasitic) are different antigens involved
in the immunological process
• Immunofluorescence microscopy reveals a granular
pattern in the glomerulus
Circulating Immune Complexes
• Ag-Ab complexes are formed in situ or in the
circulation  complexes are trapped and deposited in
the glomeruli i.e. mesangium. GBM activation of
complement and leukocyte (mainly lymphocytes)
infiltration occur proliferation of various cells i.e.
endothelial, mesangial, and epithelial cells
complexes may be degraded or phagocytosed
acute infection i.e post-streptococcal may subside.
In Situ Immune Complexes
• Classic example includes: anti- GBM Ab GN. In
which case the Ab’s are aimed at the fixed Ag in
the GBM.
• Goodpasture syndrome is an example of antiGBM Ab’s cross reacting with basement
membranes of lung alveoli and kidney
• Can cause severe glomerular damage i.e. RPGN
(rapidly progressive GN)
• Immunofluorescence microscopy will create a
linear pattern when these Ab’s deposit.
• Anti bodies can also react against antigens in
other parts of the glomerulus.
In Situ Immune Complexes
• This could be in any of the following location:
-Sub-endothelial
-Sub-epithelial
-Intra-membranous.
Antibody response against previously implanted
non glomerular antigen. E.g of such antigen
includes: DNA, bacteria protein particle such
as endostreptosin and aggregated antigenantibody complexes.
• The pattern of immunoflouresence is granular
in all of these cases.
• Molecular charge and size of the inciting agent are
important factors in determining the type of glomerular
injury.
• Proximally located complexes (endothelial or sub
endothelial location) elicit an inflammatory response
predominantly of leukocytes .Distally located Lesions
produce less inflammatory response(epithelial or sub
epithelial location)
• Complement mediated
C5a –recruits neutrophils/monocytes
C5b-9- known as MAC (membrane attack complex)
• Other mediators
monocytes/ macrophages/ platelets/ glomerular
cells i.e. epithelial, mesangial, endothelial
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Cell Mediated Immune Response
• There is a proposed theory that cell mediated
immune response plays a role in glomerular injury
• Not a proven method of glomerular injury
Mechanisms of Glomerular injury
II. Podocyte injury:
Causes of podocyte injury includes: antibodies against
podocyte antigens,Toxins or mutations affecting Nephrin
or any of the components of the slit –diaphragm.
Ab’s attach to podocyte Ag and cause effacement,
detachment of epithelial cells, and leakage of
proteins.
Mechanisms of Glomerular injury
III. Nephron Loss:
Any process that leads to nephron loss =>GFR
reduction of between 30-50% leads to end stage
renal disease.
• Adaptive changes in the remaining undamaged
nephrons , such as, hypertrophy of glomeruli =>,
hemodynamic changes and capillary hypertension.
=>Will eventually lead to further destruction of
epithelial and endothelial cells.
=>to proteinuria , glomerulosclerosis,
• Eventually, capillaries collapse and obliterate, and
glomeruli undergo segmental or global sclerosis
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Renal Pathology Outline
• Introduction
• Glomerular diseases
– Nephrotic syndrome
• Minimal change disease
• Focal segmental
glomerulosclerosis
• Membranous nephropathy
• Membranoproliferative GN
– Nephritic syndrome
• Postinfectious GN
• IgA nephropathy
Renal Pathology Outline
• Introductory stuff
• Glomerular diseases
– Nephrotic syndrome
Symptoms of Nephrotic Syndrome
• Massive
proteinuria>3.5g/day
• Hypoalbuminemia
• Edema
• Hyperlipidemia,
lipiduria
Causes of Nephrotic Syndrome
• Adults: systemic disease
(DM,SLE,Drugs,E.T.C)
• Children: minimal change disease
• Characterized by loss of foot
processes
• Response to steroids in 90% of
children
Renal Pathology Outline
• Introductory stuff
• Glomerular diseases
– Nephrotic syndrome
• Minimal change disease
Minimal Change Disease
• #1 cause of nephrotic syndrome in
children
• Loss of foot processes
• Selective proteinuria
• Pathogenesis unknown
• Good prognosis
Minimal change disease
MCD- light
microscopy
The glomeruli appear
normal
Lipid accumulation in
proximal tubule cells
may be present
Normal glomerulus
Minimal change disease
Minimal change disease
Renal Pathology Outline
• Introductory stuff
• Glomerular diseases
– Nephrotic syndrome
• Minimal change disease
• Focal segmental
glomerulosclerosis
Focal Segmental Glomerulosclerosis
Primary or secondary
Some (focal) glomeruli show partial (segmental)
hyalinization
• Unknown pathogenesis. Continuum with MCD?
Primary or Idiopathic :congenital disease,
Genetics(mutation of nephrin).
Secondary: HIV,Heroin,other nephropathies: . IgA neph.
• Hypertension and hematuria may be present (i.e
may also give nephritic picture)
• Prognosis: end stage renal disease in 50% within 10
years. Worse in adults.
'Manukura’
Focal Segmental Glomerulosclerosis
• Histology: The affected glomeruli exhibit
increased mesangial matrix, obliterated
capillary lumen, and deposition of hyaline
masses (hyalinosis) and lipid droplets.
• Occasionally, glomeruli are completely sclerosed
(global sclerosis).
• Electron microscopy: effacement of foot
processes as in MCD.
• progression =>to global sclerosis of the
glomeruli with pronounced tubular atrophy and
interstitial fibrosis.
Focal Segmental Glomerulosclerosis
Clinical disease
• Commonest cause of nephrotic syndrome
in adults(U.S, blacks)
• Presents with non selective proteinuria
Focal segmental glomerulosclerosis
Renal Pathology Outline
• Introductory stuff
• Glomerular diseases
– Nephrotic syndrome
• Minimal change disease
• Focal segmental
glomerulosclerosis
• Membranous nephropathy
Membranous Nephropathy
Summary:
• Peak age 30 and 50 years of age, Idiopathic in about 85% of
cases
• Auto immune antibodies against a yet to be identified renal
antigen.
• Slowly progressing disease
• Morphology: sub epithelial deposits (that contains
immunoglobulin's) along the GBM.
• Little or no inflammation
• Spike and dome
• Immunoflourescence: Granular pattern
• Glomeruli may appear normal by light microscopy initially =>
diffuse thickening with disease progression.
• Podocyte effacement may also be seen
Membranous nephropathy
Membranous Nephropathy
• secondary membranous nephropathy:
• Infections (chronic hepatitis B, syphilis,
schistosomiasis, malaria)
• Malignant tumors, carcinoma of the lung , colon
and melanoma
• SLE and other autoimmune conditions
• Exposure to inorganic salts (gold, mercury)
• Drugs (penicillamine, captopril, nonsteroidal
NSAIDS).
Membranous Nephropathy
Pathogenesis:
• Idiopathic forms are induced by antibodies
reacting in situ to endogenous or planted
glomerular antigens.
• Circulating immune complexes are
responsible for secondary diseases.
Membranous Nephropathy
Pathogenesis:
• Immune complex deposition activate the
c5b-9 (MAC)=>direct podocyte and
messangial cell injury=>Proteases and
Oxidant production.
• Spike and dome:Subepithelial deposits
that are separated from each other by
small, spike-like protrusions of GBM matrix
that form in reaction to the deposits.
Membranous Nephropathy
• Clinical course:
• Slowly developing disease
• Non selective proteinuria/contrast with
MCD(globulins as well as albumin lost)
• Poor steroid response
• Variable course, remission in 10-30%
• End stage renal disease in up to 40%
within 2-20 years
Membranous nephropathy
Membranoproliferative GN (MPGN)
• Characterized by alterations in the GBM and
mesangium and proliferation of glomerular cells.
• 5% to 10% of cases of idiopathic nephrotic
syndrome in children and adults.
• Some present only with hematuria or proteinuria
in the non-nephrotic range(nephritic); others
have a combined nephrotic-nephritic picture.
• Two major types of MPGN (I and II) Type I
accounts for 80% of cases)
• Different pathogenetic mechanisms responsible
for the two types of MPGN
Membranoproliferative GN (MPGN)
• Type I.
• Circulating immune complexes responsible
for most cases.
• Inciting antigen is not yet known.
Also occurs in association with :
• hepatitis B ,
• C antigenemia
• and SLE
Membranoproliferative GN (MPGN)
•
•
•
•
•
Type II
Also known as dense deposit disease
Pathogenesis unclear
Excessive complement activation
Some patients possess C3 nephritic
factor which is an autoantibody against
C3 convertase.
-It stabilizes the enzyme and prolong its
activity=>extensive alternative
pathway complement activation.
Membranoproliferative GN (MPGN)
• Type II
• Mutations affecting regulatory protein
such factor H has also been
described.=>excessive complement
activation.
• Low complement level is a feature of
type 2 disease. Due to excessive
consumption of complements as well as
reduced synthesis of factor 3 by the
liver.
• Type II
• How complement activation leads to
glomerular injury is still not very clear.
Membranoproliferative GN (MPGN)
Morphology:
• The two types of MPGN are similar on light
microscopy
• Large glomeruli ,lobular appearance with
proliferation of mesangial and endothelial
cells. There is increased cellularity.
• There is thickened basement membrane
with tram track appearance due to
apparent splitting of the GBM.
• Mesangial proliferation and interposition
causes the apparent split.
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PAS showing tram track
Membrano-proliferative GN
Type II MPGN
Intramembranous dense deposit
Morphology:E/M and Immunoflourescence
Type I
E.M
• Subendothelial
electron dense
deposit
Immunoflouresence:
• Granular pattern of
C3,IgG ,c1q-c4
seen.
Type II
E.M
• Intramembranous
very electron dense
deposit.
• Immunoflouresence:
• Linear pattern of
C3,IgG and C1q-c4
absent
• C3 nephritic factor
may be seen
Membranoproliferative GN (MPGN)
Clinical Disease
• 50% as nephrotic syndrome
• Mixed presentation also possible
• Progression to end stage disease in
40% of cases in 10 years
• Prognosis worse for dense deposit
disease.
Renal Pathology Outline
• Introductory stuff
• Glomerular diseases
– Nephrotic syndrome
• Minimal change disease
• Focal segmental
glomerulosclerosis
• Membranous nephropathy
– Nephritic syndrome
Symptoms of Nephritic Syndrome
•
•
•
•
Hematuria
Oliguria, azotemia
Hypertension
Non Nephrotic proteinuria < 3.5g/day
Causes of Nephritic Syndrome
• Post-infectious GN, IgA
nephropathy
• Immunologically-mediated
• Characterized by proliferative
changes and inflammation
Renal Pathology Outline
• Glomerular diseases
– Nephrotic syndrome
• Minimal change disease
• Focal segmental glomerulosclerosis
• Membranous nephropathy
– Nephritic syndrome
• Postinfectious GN
Post-Infectious Glomerulonephritis
•
•
•
•
•
•
Child ,1-4 weeks after strep throat
Immune complexes
Hypercellular glomeruli
Subepithelial humps
Hypo complementemia
Increased ASO titres
Post-Infectious Glomerulonephritis
“Sore throat, swollen face ,
pee coke”
Post-infectious glomerulonephritis
Post-infectious glomerulonephritis
Post-Infectious Glomerulonephritis
• Glomerular deposition of immune
complexes
• Caused by certain "nephritogenic"
strains of β-hemolytic streptococci
• Other exogenous antigens such as
staph aureus,pneumococcus,mumps
measles,chicken pox.
• Endogenous antigens from SLE may
also cause it(but more likely to give a
membranous pattern)
PSGN -IF
Post-infectious
glomerulonephritis is
immunologically
mediated,
The immune deposits
are distributed in the
capillary loops in a
granular, bumpy pattern
Renal Pathology Outline
• Introduction
• Glomerular diseases
– Nephrotic syndrome
• Minimal change disease
• Focal segmental
glomerulosclerosis
• Membranous nephropathy
– Nephritic syndrome
• Postinfectious GN
• IgA nephropathy
• A 25-years-old woman presented with 10 days
history of facial edema and no other symptoms.
She relates that one-year ago she saw the doctor
because of hematuria. She does not have fever,
weight loss.
• There was no personal or family history of major
medical problems.
• Physical examination : blood pressure: 190/100, t
Otherwise normal.
• Urinalysis revealed 60 erythrocytes HPF, proteins
4.27 g/24 h; a complete blood count was normal.
• What is your clinical diagnosis?
• What is the differential diagnosis
IgA Nephropathy
• Commonest cause of nephritic syndrome
• Bergers disease
• Child with hematuria after URI,UTI or GI
infection
• Typically recurrent hematuria even years
after the primary episode
• IgA in mesangium
• Variable prognosis
• May also cause nephrotic range
proteinuria(less common)
IgA Nephropathy
• Abnormality in IgA production and clearance.
• IgA, is at low levels in normal serum but increased in 50%
of patients with IgA nephropathy due to increased
production in the marrow.
• In addition, circulating IgA-containing immune complexes
are present in some individuals. .
• The prominent mesangial deposition of IgA suggests
entrapment of IgA immune complexes in the mesangium,
• increased frequency in celiac disease and in liver disease
• Clinical Course. Common in children and young adults.
• Nephritic-Nephrotic picture or typical nephritic syndrome
• Slow progression to chronic renal failure occurs in 25% to
50% of cases during a period of 20 years.
IgA nephropathyE/M
Electron dense deposits
can be seen in the
mesangial area
IgA nephropathy
Alport Syndrome (Hereditary Nephritis)
•
•
•
•
Hereditary nephritis
Caused by mutations in GBM proteins.
X linked disorder
Along with nephritis, Alport syndrome is
associated with nerve deafness, lens
dislocation, cataract, and corneal defects
• Mutations in any one of the alpha chains of
collagen type IV result in defective assembly
of these chains
Alport Syndrome
• Clinical findings in a female carrier will result in
asyptomatic hematuria.
• Male with the disease would present with
hematuria, proteinuria and eventual renal failure
• Microscopy : foam cells, which are due to
accumulation of fat and mucopolysaccharides in
interstitial cells.
• E/M: The GBM develops irregular foci of
thickening or attenuation with pronounced
splitting and lamination of the lamina densa,
yielding a "basket-weave" appearance.
Rapidly Progressive (Crescentic) GN (RPGN)
• Rapid decrease in GFR and loss of renal function
in weeks to several months
• Major pathologic finding :extensive glomerular
crescent formation within Bowman’s space
• due to proliferation of the parietal epithelial cells
of Bowman’s capsule
• These crescents are composed of parietal
epithelial cells, macrophages, monocytes, and
fibrin
• It may be associated with other diseases or it
may be idiopathic
RPGN
• Three main types of RPGN, based upon the
immunological process:
1)Type I- Anti-GBM Ab- Goodpasture syndrome
2)Type II-Immune complex-poststreptococcal, SLE,
HSP,
IgA nephropathy
3)Type III- Pauci immune –ANCA associatedWegener
granulomatosis, microscopic
angiitis
• On immunofluorescence, granular or linear deposits
of immunoglobulins may be present +/- complement
• Electron microscopy may show GBM disruption
RPGN
Clinical findings includes:
• nephritic syndrome
• severe oliguria
• Poor prognosis with rapid progression
to renal failure
• Long term dialysis or transplantation
may be required
RPGN – M/E
There are epithelial
crescents squashing the
glomerular tufts from all
sides.
RPGN may be idiopathic
or may result from SLE,
post-infectious GN (as in
some cases of postinfectious GN), from
various types of
vasculitis, and from
Goodpasture syndrome.
Type I RPGN
• This is characterized deposits of IgG and C3 on the
GBM .
• Note: anti-GBM Ab’s also deposit on the pulmonary
alveolar basement membrane => pulmonary
hemorrhage and renal failure- known as Goodpasture
syndrome
• In idiopathic cases, there is only renal involvement.
• Treatment: plasmapheresis
Type I RPGNGoodpasture
syndrome- IF
There is strong linear
reactivity for IgG along
the glomerular basement
membranes.
Type II RPGN
• These are characterized by the presence of immune
complexes
• An underlying cause i.e. poststreptococcal GN, IgA
nephropathy,etc. may be present
• Immunofluorescence reveals a granular (“lumpy
bumpy”) pattern on the GBM or mesangium
Type III RPGN
• This is also known as pauci immune RPGN
• No significant immune complex or anti-GBM Ab
deposition seen on immunofluorescence or electron
microscopy
• There is the presence of ANCA in the serum of these
individuals
• Vasculitides i.e. Wegener granulomatosis and
microscopic angiitis play a role in the pathogenesis of
renal disease
• Severe segmental necrosis may be seen in the
glomeruli
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Chronic GN
Important cause of end stage renal disease (ESRD)
characterized by chronic renal failure and uremia
• Clinical features:
• Hypertension,
• Proteinuria,
• Azotemia,
• Anemia,
• Nephritic or Nephrotic syndrome
• The glomeruli get obliterated and the degree of
proteinuria decreases with disease progression.
• Treatment with renal dialysis and transplantation .
• Prognosis is poor .
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Diabetes Nephropathy
• Glomerular lesions are the commonest cause of
end stage renal disease in Diabetes
• Three major patterns of Glomerular disease:
• -Non Nephrotic Proteinuria
• -Nephrotic syndrome
• Chronic renal failure
• Diabetes also affects the arterioles.
Characteristically involving both the afferent and
efferent arterioles. Efferent arterioles are not
affected in non diabetics.
Diabetes Glomerulonephritis
• Pathogenesis
• D/M Microangiopathy (small vessel disease)is
responsible.
1.Metabolic effect=>Hyperglycemia=> None
enzymatic glycosylation of proteins=>AGE.
=> Increased type IV collagen in the GBM and
decreased Heparan sulfate=>thickened GBM,
increased mesangial matrix.
2.Hemodynamic effects. Initial GFR
increase=>glomerular
hypertrophy=>glomeruloscleorsosis
Diabetes Glomerulonephritis
• Morphology:3 main lesions
1. Capillary Basement Membrane
Thickening:Thickening of basement membrane
occurs in all diabetics.
• Starts from 2 – 5 years of D/M onset
• Detectible only by E/M.
2. Diffuse Mesangial Sclerosis:
• Diffuse progressive increase in mesangial matrix
• The mesangial depositions are PAS positive
• Mesangial cell proliferation is not significant.
• May also be seen in old age and hypertension.
Diabetes Glomerulonephritis
3.Nodular sclerosis otherwise known as
Kimmelstiel-Wilson Disease
• Ball like deposits of PAS positive
laminated matrix located in the
periphery of the glomerulus.
• Usually contained trapped mesangial
cells.
• Seen in 15-30% of long term diabetics
• More Pathognomonic of D/m than
diffuse sclerosis.
Exudative lesions in D/m Fibrin Cap.Hyaline deposits in the
peripheral tufts of capillaries.
Exudative Lesions of D/M. capsular drop.Hyalin deposits in
bowmans capsule.
Chronic GN-gross
In ESRD, the kidneys are
small and shrunken
bilaterally, as shown
here.
Chronic GN- micro
There is interstial
fibrosis, the glomeruli
are sclerotic, and there
are scattered chronic
inflammatory cell
infiltrates
Tubulointerstitial nephritis
• Kidney diseases that involve structures in the kidney
apart from the glomerulus.
Two main categories:
• Pyelonephritis
• Interstitial Nephritis
Renal Pathology Outline
• Introductory stuff
• Glomerular diseases
• Tubular and interstitial diseases
– Tubulo-interstitial Nephritis
• pyelonephritis
• drug-induced interstitial nephritis
– Toxic/ischemic lesions
• Acute tubular necrosis
Renal Pathology Outline
• Introductory stuff
• Glomerular diseases
• Tubular and interstitial
diseases
– Inflammatory lesions
• pyelonephritis
Pyelonephritis
• Invasive suppurative infection of the
kidneys and the renal pelvis.
• Usually ascends from UTI
• Fever, flank pain
• Hematogenous spread is also possible
in the immuno-compromised,severe
sepsis and debilitated pateients.
Organisms:
• E. coli, Proteus,enterobacter
,Pseudomonas
• Urinary tract mainipulations,anomalies
of the lower urinary tract
Acute Pyelonephritis
Pathogenesis
• Bacteria can reach the kidneys via two
pathways: the bloodstream or the lower
urinary tract (ascending infection)
• Ascending infection from the lower urinary
tract (most important route) :
bacteria adhere to the mucosa colonize
distal urethra (introitus in females) gain
bladder accessmove upstream against
flow of urine ascend ureters and enter
pelvis of kidney
Acute Pyelonephritis
Pathogenesis
Predisposing factors for infection include:
• access to bladder via instrumentation i.e.
catheterization and cystoscopy
• females :short urethra,urethral trauma during
intercourse,
• outflow obstruction or bladder dysfunction
may lead to stasis and lead to multiplication
of bacteria
• VUR (vesicoureteral reflux)- most important.
• congenital or acquired
-congenital- defective ureterovesical valve
Acute Pyelonephritisgross
There is a variable
number of small ,
yellowish abscesses
scattered over the renal
surface
The kidney may be
normal sized or enlarged
Acute Pyelonephritis
• Clinical findings: fever, chills, malaise
costovertebral tenderness
urinary symptoms: dysuria,
frequency, and urgency
urinalysis: pyuria and WBC casts
Complications: chronic pyelonephritis
papillary necrosis
perinephric abscess
Acute pyelonephritismicro
Numerous PMN's are
seen filling renal tubules
Acute pyelonephritis
Cellular cast
• White cell cast differentiates between
pyelonephritis and a mere UTI.
Chronic pyelonephritis
• Renal injury induced by recurrent or persistent
renal infection.
• Associated with progressive renal scarring, which
can lead to end-stage renal disease (ESRD)
• Continuous damage and scarring of renal
parenchyma=>ESRD
• There are two types:1) chronic obstructive
pyelonephritis- recurrent infections, due to
obstruction, lead to renal failure
2) reflux nephropathy- this is
due to VUR, which causes chronic renal damage
Chronic Pyelonephritis con’t
• Hallmark of chronic pyelonephritis is scarring of pelvis
or calyces, which leads to papillary blunting and an
asymmetric ally contracted kidney
• Clinical findings and diagnosis:
hypertension
ultrasound-looks at size and shape of kidney
Chronic pyelonephritis
Drug-Induced Interstitial Nephritis
• Antibiotics, NSAIDS
• IgE and T-cell-mediated immune
reaction
• Fever, eosinophilia, hematuria
• Patient usually recovers
• Analgesic nephritis is different
(bad)
Drug Induced Nephritis
• Injury to the kidney can be caused by a number of drugs,
which include:
penicillin (ampicillin, methicillin)
rifampin
NSAIDS
Pathogenesis: - Type I (eosinophilia and rash) and Type IV
hypersensitivity reactions ( granulomatous
reaction)
-drugs act as haptens, which bind tubular
cells and become immunogenic
Microscopically, there is infiltration by lymphocytes,
neutrophils and eosinophils. Granulomas may be present.
Drug Induced Nephritis
• Clinical findings include: fever
eosinophila
rash
hematuria
proteinuria +/Note: complete recovery of renal function can
occur
following cessation of drug
intake
Drug-induced interstitial nephritis
Analgesic Nephropathy
• Chronic usage of analgesic mixtures leads to
papillary necrosis.
• Drugs implicated include:
Aspirin inhibits the vasodilatory action of PGE2
and causes ischemia
Acetaminophen causes free radical formation
that damage renal tubules.
• Pathogenesis: papillary necrosis followed by
interstitial nephritis
• Clinical findings: gross hematuria , proteinuria
• Increased risk of transitional cell carcinoma of the
renal pelvis in survivors
Acute Tubular Necrosis
• The most common cause of ARF!
• Reversible tubular injury
• Many causes: ischemic (shock),
toxic (drugs)
• Most patients recover
Acute Tubular Necrosis (ATN)
• ATN is a renal disorder involving damage to
the tubular epithelial cells.
• It is the most common causes of acute renal
failure, which is manifested by anuria or
oliguria( < 400 ml/24hrs)
• ATN usually occurs after an acute ischemic or
toxic event. Examples include: septicemia,
acute pancreatitis, hemorrhage, trauma, etc.
ATN
• There are two types of patterns seen in ATN:
1. Ischemic ATN
2. Nephrotoxic ATN
• Ischemic ATN
Hypovolemia and shock are the most common
causes of ischemic ATN
Ischemia damages endothelial cells.
Causes decrease in vasodilators i.e. nitric oxide, PGI2
Increase in vasoconstrictors i.e endothelin
These effects lead to vasoconstriction of afferent
arterioles, which decrease GFR.
ATN
• Nephrotoxic type
Causes include:
Aminoglycosides i.e. gentamicin
Radiographic contrast agents
Heavy metals (i.e. lead and mercury)
Organic solvents ( carbon tetrachloride)
ATN
Pathogenesis:
Toxins or anoxia causes shedding of
tubular cells into the urine  continual
injury leads to further damage of tubules
tubular debris (casts) accumulates leads
to increased intra-tubular pressure fluid
is pushed into interstitium GFR is
reduced
Final result: oliguria
Note: necrosis of tubular segments leads to
the production
of proteinaceous
casts- brown colored granular casts
ATN
•
•
•
•
•
•
•
•
•
Clinical findings:
Well-defined sequence of events.
Initiation phase- (first 36 hours)
Acute decrease in GFR (and oliguria)
Sudden increase in serum creatinine and blood urea
nitrogen (BUN) concentrations.
The maintenance phase (first week)
Sustained severe reduction in GFR,
continues for a variable length of time(about 1-2
weeks.)
Oliguria and increased BUN/creatinine persists
ATN
• The recovery phase,
• Tubular function is restored,
• Increase in urine volume (up to a few liters a
day)
• there is an increased susceptibility to
infection thus, a higher mortality rate
• Renal function is restored and urine output
returns to normal.
• Some kidney abnormalities may persist for
several months.
• With appropriate therapy, there is a good
prognosis
Acute tubular necrosis
Acute tubular necrosis
Urinary Tract Infection
• Women, elderly
• Patients with catheters or
malformations
• Dysuria, frequency
• Organisms: E. coli, Proteus
UTI: Common Bugs
E. coli
uncomplicated
complicated
Urinary catheter colonized by Proteus
Renal Pathology Outline
• Introduction
• Glomerular diseases
• Tubular and interstitial diseases
• Diseases involving blood vessels
– Benign nephrosclerosis
– Malignant nephrosclerosis
Benign Nephrosclerosis
• Found in patients with benign
hypertension
• Hyaline thickening of arterial walls
• Leads to mild functional impairment
• Rarely fatal
• Affects only afferent arterioles
• When seen in daibetes affects both
afferent and efferent arterioles
Benign nephrosclerosis
Malignant Nephrosclerosis
• Arises in malignant
hypertension
• Hyperplastic vessels
• Ischemia of kidney
• “Flea beaten”kidney on gross
appearance
• Medical emergency
Malignant Hypertension
• 5% of cases of hypertension
• Super-high blood pressure, encephalopathy,
heart abnormalities
• First sign often headache, scotomas
• Decreased blood flow to kidney leads to
increased renin, which leads to increased BP!
• 5y survival: 50%
• Histology:Necrotising arteriolitis
Malignant nephrosclerosis
Malignant nephrosclerosis
Renal Pathology Outline
• Introductory stuff
• Glomerular diseases
• Tubular and interstitial diseases
• Diseases involving blood vessels
• Cystic diseases
– Adult polycystic kidney disease
– Childhood polycystic kidney disease
Adult Polycystic Kidney Disease
•
•
•
•
Autosomal dominant
Huge kidneys full of cysts
Usually no symptoms until 30s
Associated with berry aneurysms
and Hypertension
• Germline mutation affecting PKD1
gene on chromosome 16(85-90).
or PKD2 gene on chromosome
4(15%)
ADPKD
• Cysts can be formed anywhere in the kidney
i.e. tubules, collecting ducts, bowman’s
space, etc.
• Expanding cysts cause pressure on the
surrounding tissues and lead to ischemic
changes
Adult polycystic kidney disease
ADPKD
• Clinical findings:
- Most patients remain asymptomatic until middle age
- Abdominal mass – massive bilateral kidney
enlargement
- Flank pain
- Hypertension
- Gross hematuria
- Berry aneurysms, liver cysts are extrarenal findings
• Diagnosis: ultrasound
• Most patients develop end stage renal failure
Childhood Polycystic Kidney Disease
• Autosomal recessive
• Numerous small cortical
cysts
• Associated with liver cysts
• Patients often die in
infancy
Autosomal Recessive (Childhood) Polycystic
Kidney disease
• This rare disease has a autosomal recessive pattern,
which result from a mutation in the PKHD1 genecodes for the fibrocystin gene on chromosome 6
• It presents bilaterally as small cysts, which are
usually found in the cortex and medulla- give a
spongelike appearance
• Cysts may be found in the liver
• There is a high mortality rate associated with with
neonates or young infants. In the surviving patient,
liver cirrhosis will ensue
Childhood polycystic kidney disease
Urinary Outflow Obstruction
Renal stones
-passage of a urinary stone is a frequent cause of
obstruction to urinary tract
-calculus (stone formation) can occur anywhere along the
urinary tract
The first phenomenon is supersaturation of the urine by
stone-forming constituents, including calcium, oxalate, and
uric acid.
Crystals or foreign bodies can act as nidi, upon which the
supersaturated urine form microscopic crystalline structures
-
Urinary Outflow Obstruction con’t
• Composition of renal stones:
1. calcium oxalate or calcium oxalate + calcium
phosphate (approximately 80 %)
2. magnesium ammonium phosphate (struvite
stones) (approximately 10 %)
3. Uric acid (approximately 6 -7%)
4. Cystine stones (approximately 1-2%)
Urinary Outflow Obstruction con’t
• Pathogenesis
Calcium containing stones (calcium oxalate, calcium
phosphate)
- Idiopathic hypercalciuria occurs in more than one half of
patients with calcium oxalate stones. Most causes of
hypercalciuria are absorptive
-Increased absorption in individuals after a normal diet
causes an elevation of serum calcium levels
-Hypercalcemia due to hyperparathyroidism, sarcoidosis,
vitamin D intoxication
-The presence of uric acid , oxalates, and citrates in the
urine provide a conducive environment for calcium
deposition
- Crystallization of calcium phosphate stones occurs in a high
pH
Urinary Outflow Obstruction con’t
Magnesium ammonium phosphate (struvite stones)
- Urinary tract infections provide an alkaline
environment, which naturally cause urea splitting
bacteria i.e. Proteus vulgaris to flourish
-deposition in the kidney creates a cast in the renal
pelvis and calyces, which is known as staghorn calculi
Uric acid stones
• Hyperuricemia due to gout or leukemias
• The most important determining factor in uric stone
production the presence of acidic urine-
Urinary Outflow Obstruction con’t
Cystine stones
-there is a defect in renal transport of cystine
Clinical findings:
-The patient may remain asymptomatic until a small
stone passes out into the ureter. This typically
causes a colicky pain, which radiates to the groin
-Gross hematuria
-Obstruction caused by stones leads to infection
- Xray shows radiopaque calcium stones
Urolithiasis-CXR
Radiopaque stones can
be seen in this xray
These are are composed
of calcium
Staghorn calculi
This is an x-ray of
staghorn calculi
Hydronephrosis
• Hydronephrosis is defined as a dilation of the renal
pelvis and calyces, due to the interruption of urine
outflow
• The obstruction can be anywhere along the urinary
tract
• Causes include:
congenital- urethral atresia, kinked ureter, etc.
acquired- stones, carcinoma prostate, BPH, spinal
cord damage, prostatitis, ureteritis
Hydronephrosis
• Can be unilateral or bilateral. It is bilateral if the
obstruction is below the level of the urethra; and, it is
unilateral if it is above.
• Pathogenesis:
If the flow of urine is obstructed, urine backs up behind
the point of blockage, eventually reaching the small tubes
of the kidney and renal pelvis
Continued filtration (GFR) and back pressure (due to the
obstruction) cause compression of the renal vasculature
Obstruction leads to tubular dysfunction and reduction in
GFR
Hydronephrosis con’t
• Bilateral hydronephrosis leads to renal failure. In contrast,
unilateral hydronephrosis causes an enlarged kidney
• There is atrophy and compression of renal parenchyma,
along with loss of papillae and flattening of the pyramids
• Hydroureter may result depending upon the level of
obstruction
• On M/E: tubular dilation/ atrophy and fibrosis of tubular
epithelium/ loss of glomeruli (late finding), papillary
necrosis eventually, cortical atrophy progresses to the
point at which only a thin rim of parenchyma is present
Hydronephrosis
• Clinical findings:
-obstruction bilaterally leads to anuria
-obstruction unilaterally may be asymptomatic
-with acute obstruction, patients may present
with
pain, which is usually described as severe,
intermittent, and dull
Hydronephrosisgross
The cut surface shows a
very thin rim of cortex
The area of the pelvis
and calyx are distended,
and large cystic spaces
occupy the pyramids.
The ureter is dilated.
Renal Pathology Outline
• Introductory stuff
• Glomerular diseases
• Tubular and interstitial
diseases
• Diseases involving blood
vessels
• Cystic diseases
Renal Cell Carcinoma
• Renal cell carcinoma accounts for 3 % of all
malignancies
• The tissue of origin for renal cell carcinoma
is the proximal renal tubular epithelium
• Risk factors include: smoking,
hypertension, cadmium exposure, obesity
• The classification of the three most
common types of tumors is based upon
genetic predisposition
RCC con’t
• The three most common types of RCC include:
1. Clear cell carcinoma
2. Papillary renal cell carcinoma
3. Chromophobe renal carcinoma
RCC con’t
• Clear cell carcinoma
-This is the most common type ( 70-80%)
-As the name suggests, it is made up of cells
with clear or granular cytoplasm
-There may be an association with von Hippel
Lindau (VHL) disease
-VHL is an autosomal dominant disease that
is characterized by cerebellar or retinal
hemangioblastomas
- Clear cell carcinoma presents as bilateral
and multiple cysts
RCC
Clear cell carcinoma con’t
-VHL gene (tumor suppressor gene) is present on
chromosome 3 (3p25) and an individual inherits the germ
line mutation.
-Somatic “hit” or somatic mutation causes the loss of the
second allele. This leads to clear cell mutation, by
uncontrolled tumor growth and angiogenesis
-The tumor invades the renal vein, as it enlarges and
extends through the kidney to reach other parts of the
body- IVC penetration and invade the heart
-they can metastasize to lungs (most frequent) and bone
(causes lytic lesions)
RCC con’t
• Papillary Renal Cell Carcinoma
- They make up 10-15 % of all renal cancers
- These tumors are multifocal and bilateral;
they have a papillary growth pattern
-It is associated with the METprotooncogene, which is located on
chromosome 7 (7q31)
- Grossly, they appear as a yellow mass, but
to a lesser degree than clear cell carcinoma
(due to lower lipid content)
RCC con’t
• Chromophobe Renal Carcinoma
- These tumors represent 5 % of all renal cell carcinomas
-They are made up of intercalated cells of the collecting
duct.
-Grossly, the tumor appears tan brown. Microscopically,
nuclei are surrounded by clear cytoplasm
-This type of tumor has many missing chromosomes i.e.
chromosomes 1,2 6, 10, 13, 17, and 21. This leads to
hypodiploidy
-This tumor has a good prognosis
This photograph shows
the cut surface of a
kidney
There is a large renal
cell carcinoma in the
upper pole with bright
yellow areas, areas of
hemorrhage, and tan
and white areas
They appear as spherical
masses
RCC (clear cell
carcinoma)- M/E
The malignant cells have
abundant clear or empty
appearing cytoplasm
The tumor may appear
vacuolated or solid
RCC con’t
• Clinical findings:
-triad of :
painless hematuria, palpable abdominal mass,
and dull flank pain
-fever
-polycythemia-erythropoiesis
-paraneoplastic syndrome:
hypertension, hypercalcemia, Cushing
syndrome
Renal cell carcinoma
Renal cell carcinoma
Renal cell carcinoma