Lab 3, Case 1Case 1: A father brings in his 2.5-year-old daughter because she has had puffy

eyes for the last two days. A week prior to her presentation she had an upper respiratory tract infection. On exam she is afebrile with a blood pressure of 90/60 mmHg (normal). She has periorbital and ankle edema bilaterally but no rashes or bruising. Her family history is positive only for a paternal grandfather with nephrolithiasis.

Questions:1. What are the potential causes of edema in this girl?

2. What additional information do you need to narrow down the differential diagnosis (e.g., physical exam findings, lab tests, imaging studies)?

3. Is this clinical presentation consistent with nephritic or nephritic syndrome? Why?

4. What would the renal biopsy show and when is a biopsy indicated?

H&E stain of kidney biopsy specimen, low magnification

H&E stain of glomerulus, high magnification

Jones’ silver stains matrix of GBM, mesangia, Bowman’s capsule & TBM

Jones’ silver stains matrix of GBM, mesangia & Bowman’s capsule

Direct immunofluorescence of glomerulus labeled with anti-IgG

normal for comparison patient’s biopsy

Electron microscopy – note podocyte foot processes

vascularlumen

urinaryspace

urinaryspace

vascularlumen

vascularlumen

urinaryurinaryspacespace

vascularvascularlumenlumen

podocytepodocyteurinaryurinaryspacespace

vascularvascularlumenlumen

vascularvascularlumenlumen

mesangiummesangium

urinaryspace

vascularlumen

vascularlumen

vascularlumen

podocytepodocyte

podocytepodocyte

podocytepodocyte

podocytepodocyte

podocytepodocyte

Electron microscopy – note podocyte foot processes

vascularlumen

urinaryspace

podocytepodocytenucleusnucleus

fenestratedfenestratedendotheliumendothelium

Lab 3, Case 2A primary care physician refers a patient to you for consultation. This 50-year-

old African-American male is an electrical engineer who is working on the new Clarian Pathology building at 10th and West streets. He is otherwise healthy except for mild hypertension and new leg edema up to his knees. The edema has not improved with anti-diuretic therapy and salt restriction as previously prescribed by his physician. He began smoking during a 3-year tour in the Navy and now has a 35-pack-year history. There are no known risk factors for HIV, hepatitis B or hepatitis C. His family history is unremarkable except for his father who died of colon cancer at age 60.

Questions1. What are the potential causes of edema in this adult male? What is the

importance of viral risk factors in a patient with edema?

2. What additional information do you need to narrow down the differential diagnosis (physical exam findings, lab tests, imaging studies)?

3. What clinical syndrome does this clinical presentation represent?

4. What might the renal biopsy show and when is a biopsy indicated?

H&E stain of glomerulus – note thick capillary loops – why?

vascular pole

H&E stain of glomerulus H&E stain of glomerulus –– note thick capillary loops note thick capillary loops

Jones’ silver stain of glomerulus – compare to case #1 in lab #1

The silver stain helps to explain why the capillary loops appear thickened on the H&E

Direct immunofluorescence with anti-IgG (low magnification)

Direct immunofluorescence with anti-IgG (high magnification of capillary loops)

Electron microscopy of capillary loop

Correlate EM to vacuoles seen on silver stain of glomerulus

urinaryurinaryspacespace

vascularlumen

Electron microscopy of capillary loop (more advanced disease)

vascularlumen

podocyte withpseudovilli

urinary space

endothelial cell

Lab 3, Case 327-year-old Biochemistry graduate student from Japan presents with

complaints of bloody urine over the past 24 hours. He developed an upper respiratory infection two days ago but is not febrile. The patient also recalls a similar episode about six years prior to this occurrence. His exam is normal except for clear rhinorrhea and a blood pressure of 148/98 mmHg. His family history is negative.

Questions:1. What are the potential sources for blood in the urine of this patient? How

would you differentiate between these possibilities based on theurinalysis?

2. How can you narrow down the differential diagnosis at this stage? What laboratory tests would you order?

3. How would you evaluate the extent of injury to the kidney? 4. What test or procedure would provide definitive information that would

assist you in your management of this case?5. What is the importance of the negative family history for renal diseases? 6. Would you perform a renal biopsy on this patient?7. If you perform a renal biopsy what would you expect to be the

characteristic pathology?

H&E of glomerulus – cellularity is increased – where?

H&E of glomerulus – cellularity is increased – where?

H&E anti-fibrinogen

Jones’ silver stain of glomerulus – what’s happening in Bowman’s space?

What is this ‘tail’?

Direct immunofluorescence of glomerulus with anti-IgA

Mesangial or capillary loop labeling?

Direct immunofluorescence with anti-IgA

Mesangial or capillary loop labeling?

What is this electron dense ‘stuff’ in the mesangium?

RBC RBC

urinaryspace

vascularlumen

vascularlumen

RBC

RBC

RBCpo

docy

te

podocyte