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What Every
M e d i c a l
Student Needsto Know About . . .
What Every
M e d i c a l
Student Needsto Know About . . .
Roger S. Riley, M.D., Ph.D.
November , 2001
Renal
Pa tho logy
Renal
Pa tho logy
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Second a ry G lom eru la r D isea sesSecond a ry G lom eru la r D isea ses
s Acute proliferative
glomerulonephritis
s Lupus nephritis
s Diabetic glomerulosclerosis
s Renal amyloidosis
s Chronic glomerulosclerosis
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Pa t ie n t G .C.Pa t ie n t G .C.
s 16 year old, female, student
s History: Weakness
urine output x 2 days
Recent history of sore throat, URI
s Physical: Mild peripheral edema
s Urinalysis: 2 protein
10 RBC/HPF
Frequent RBC casts
Few hyaline and granular casts
s Lab Data: BUN - 45 mg/dLCreatinine - 6.3 mg/dL
H/H - 8.2/28.5
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IgGIgG
C3C3
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Acute Post-Streptococcal GNAcute Post-Streptococcal GN
Synonyms:
Incidence:
Etiology:
Clinical:
Lab:
Path:
Clinical
Course:
Acute prol iferat ive glomerulonephri tis,
acute post-infectious GN.
Glomerular trapping of circulating anti-
streptococcal immune complexes. Group A,
B-hemolytic streptococci, type 12.
Acute nephrit ic syndrome post-s trept
pharyngitis or pyoderma. Other infections.Nephri tic urine with RBC casts. Evidence
of st reptococcal infection or serologic
evidence of recent infection. Decreased
serum complement.
Children - Excellent prognosis. Adults -
Worse prognosis, some develop
progressive disease.
Enlarged, hypercellular glomeruli with
endothelial and mesangial cell
prol iferation. Acute inflammation. IgG andC3 in very coarsely granular pattern along
GBMs. Discrete, subepithelial hump-like
deposits.
Peak incidence in children (3-14). Sporatic,
mostly winter and spring.
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Post-Streptococcal GNPost-Streptococcal GN
CNS
+ Strep Assay
Hypertension
Proteinuria
Hematuria
Streptococcal
Infection
Latent Period
Acute Nephritis
Edema
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Lupus NephritisLupus NephritisIncidence:
Etiology:
Clinical
Features:
Lab:
Path:
Clinical
Course:
Auto immune disorder with denatured
DNA as the antigen.
Poor disease prognosis with renal
involvement. Crescent formation more
omnious. Renal disease is cause of death
in 30%. Recurs in transplanted kidneys.
Six types of glomerular disease by WHO
classification. (I) Normal glomerul i, (II) Pure
mesangial alterations, (III) Focal segmental
glomeuulonephritis, (IV) Diffuse
glomerulonephritis, (V) Diffusemembranous glomerulonephritis, (VI)
Advanced sclerosing glomerulonephrit is .
Common, autoimmune, multi-system
disease. Black, female bias. Renal
involvement in > 70% SLE patients,
common cause of death.
Skin, GI, and renal. May present as
nephrotic or acute nephritic syndrome.
Hematuria, RBC casts, some proteinuria.Positive assays for anti-nuclear and anti-
DNA antibodies.
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Patient T.R.Patient T.R.
s 25 year-old auto mechanic
s History: urine output x 10 days
Hematuria x 2 days
Headaches, myalgia, lassitude
s Physical: Obesity, mild HTNs Urinalysis: 3 protein
Many RBCs, RBC casts
s Lab Data: BUN - 102 mg/dL
Creatinine - 10.2 mg/dL
Total protein 5.9 g/dL
H/H - 12.5/28.4
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The Biopsy
showed
anti-GBM Disease !
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Anti-GBM DiseaseAnti-GBM Disease
Synonyms:
Incidence:Etiology:
Clinical
Features:
Lab:
Path:
Clinical
Course:
Goodpastures Syndrome.
Anti -renal /pu lmonary BM Abs.
Inflammation and complement.
Acute nephr it ic syndrome with very rapid
disease progression Hemoptysis usually
present. Frequent history of preceeding
viral-like illness. History of exposure to
volatile hydrocarbons in some patients.
Nephritic urine with RBC casts. Positive
assay for anti -GBM antibodies.
Progression to ESRD in 1-2 years in >
90% patients. High in itial mortality rate.
Aggressive Rx with steroids,
plasmapheresis, and cytotoxic therapy
mandatory.
Proliferative and necrotizing GN with
crescent formation. Extensive interstitial
inflammatory infiltrates. Diffuse, linear IgG
deposits outlining GBMs.
Primarily 2nd to 4th decade. Males.
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Pa t ien t L.M .Pa t ien t L.M .
s 65 year old females History: Recent anemia and proteinuria
History of ASCVD & hypothyroidism
History of adult-onset diabetes
s Physical: Moderate obesity
s Urinalysis: 4 protein
3-5 WBCs/HPF
Few granular, hyaline casts
Few WBC casts
s Lab data: BUN - 49 mg/dL
Creatinine - 4.8 mg/dL
Hgb - 8.3 g/dL
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H&EH&E
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H&EH&E
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PASPAS
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H&EH&E
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H&EH&E
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Mrs. M.
has
diabetic glomerulosclerosis!
Di b ti Gl l l iDiabeticGlomer losclerosis
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Diabetic GlomerulosclerosisDiabetic Glomerulosclerosis
Synonyms:
Incidence:
Etiology:
Clinical
Features:
Lab:
Path:
Clinical
Course:
Kimmelstiel-Wilson disease.
Renal disease secondary to diabetic
microangiopathy, with thickening of BMs.
Related to DM severity/duration.
Gradual progression to ESRD, usually
within six years. Progression slowed with
control of hyperglycemia. Transplantation
is option.
Gross - Small, contracted kidneys with
granular sur face. Diffuse diabetic
glomerulosclerosis - Increased mesangial
matrix, thickened BMs, hyaline arteriosclerosis
of afferent and efferent arterioles. Nodular
diabetic glomerulosc lerosis - Same as diffuseform + mesangial nodules (Kimmelstiel-Wilson
lesion). Marked GBM thickening.
Common cause of renal failure in
diabetics. 30-50% IDDM patients.
Proteinuria is major manifestation, nephrotic
syndrome may develop. Hypertension andmicroscopic hematuria.
Proteinur ia hematur ia. Elevated glucose,
BUN, creatinine.
Diffuse
Nodular
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Pa t ie nt L.G.Pa t ie n t L.G.
s 81 year old females History: Progressive L.E. edema x 5 mos.
Multiple recent UTIs
History of hypertension
s Physical: Pitting L.E. edema to mid-calf
s Urinalysis: 4 proteinHyaline casts and gitter cells
12 grams protein/24 hrs.
s Lab data : BUN - 35 mg/dL
Creatinine - 2.0 mg/dL
Serum total protein - 3.4 g/dL
Serum cholesterol - 308 mg/dL
ESR - 107 mm/hr
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PASPAS
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PASPAS
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Anti-Lambda
Anti-Lambda
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Th bi
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The biopsy
Showed a myeloma
kidney!
Renal Disease in Plasma Cell DyscrasiaRenal Disease in Plasma Cell Dyscrasia
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a s as as a C ys as ay
Synonyms:
Incidence:
Etiology:
Clinical:
Lab:
Path:
Clinical
Course:
Myeloma kidney.
Deposition of monoclonal immunoglobulins or
Ig light chains in glomeruli or
tubulointerstitium.
Poor prognosis. Transplantation contraindicated.
LM - Ig deposits , may be nodular. Light chains
may deposit as amyloid or precipitate as hard
casts. Membranous or proliferative pattern
possible. Cryoglobulins produce microthrombi.
IgM deposits in Waldenstroms. IF -
Autofluorescence. + kappa or lambda stain. EM
- Amyloid may be identified.
Common in patients with plasma celldyscrasias.
Proteinuria, nephrotic syndrome, or renal
insufficiency.Proteinuria, increased renal s ize, abnormal
serum and/or urine protein electrophoresis.
Renal AmyloidosisRenal Amyloidosis
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Renal AmyloidosisRenal Amyloidosis
Incidence:
Etiology:
ClinicalFeatures:
Lab:
Path:
Clinical
Course:
Disorder of protein metabolism with
extracellular deposits of amyloid. Amyloid is
a proteinaceous material with a beta-pleated
structure. Four biochemical forms of
amyloid, all with identical light and
ultrastructural features.
Poor prognosis , especially primary form.
Death usually from other manifestations of
amyloidosis. Transplantation
contraindicated.
Amyloid deposi ts in mesangium and small
vessels, later in GBM. Congo red stain
shows apple-green birefringence under
polarized light. Small, nonbranched fibrilswith criss-cross ( felt-like ) pattern, 7-10
nm.
Common in patients with amyloidosis.
Proteinuria, nephrotic syndrome, or renalinsufficiency common, especially in primary
(idiopathic) form. Hypertension.
Proteinur ia, increased renal size.
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Congo Red
Congo Red
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ChronicGlomerulosclerosisChronicGlomerulosclerosis
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Chronic GlomerulosclerosisChronic Glomerulosclerosis
Synonyms:
Incidence:
Etiology:
Clinical
Features:
Lab:
Path:
Clinical
Course:
End-stage renal d isease, dif fusesclerosing glomerulonephritis
The pathogenesis usually cannot be
determined.
Both sexes, all ages and races. A history
of a preceeding renal disease is present
in many patients.
Severe renal failure. Uusually no diagnostic
findings of a specific renal disease.
Irreversible, progressive renal failure.Treatment options are chronic dialysis or
renal transplantation.
Small contracted kidneys. Diffuse, global
hyaline sclerosis of glomeruli accompanied
by marked tubular atrophy, patchy
interstitial fibrosis, and interstitiallymphocytic infiltrate.
End-stage of many renal d iseases.
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