renal path lecture 3

7/28/2019 Renal Path Lecture 3

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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


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


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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renal path lecture 3

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