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Genito-Urinary

Tract Module

University of Santo Tomas


Faculty of Medicine and Surgery
Department of Pathology
Pathology of the Kidney
Part 1

Diseases of the Glomerulus

by
Normando C. Gonzaga, M.D., FPSP
Objectives
• To analyze clinical manifestations of renal
diseases utilizing the steps of science
• To be aware of the common glomerular
diseases seen in the Country
• To recognize and describe the gross and light
microscopic appearances of glomerular lesions
• Correlate the above with immunofluorescense
and electron microscopic findings
• To explain the pathogenesis of these lesions
utilizing the basic principles of pathology
• To make a clinico-pathologic correlation
Urine is an ultrafiltrate of plasma.

Blood Cross-section of Urine


Kidney
1. Identify and describe the gross of a
normal kidney.
2. Discuss briefly the gross, microscopic,
and biochemical characteristics of blood
and urine, and their salient differences.
Urine is formed by the nephron. Discuss briefly the formation
of urine.

Blood

Urine
Using the illustration at the left picture, identify the different
components of the normal glomerulus at the right picture as
labeled in the illustration. Identify the lobule and describe the
cellularity.
Below is the PAS stain of a normal glomerulus showing the
normal thickness of the basement membrane. Study the
morphology of the normal glomerulus. This will be used as
reference in recognizing the different light microscopic
abnormalities.
An electron micrograph of the normal glomerulus. Study the
different components especially their relationship with one
another. What are the functions of the mesangial cells?
Another electron micrograph of the glomerulus. Study the
mesangial cells, endothelial cells, and the foot processes,
and their relationship with one another.
Lower magnification of the foot processes, basement
membrane, and visceral epithelial cell. Study well the
structural appearance of the foot processes.
E.M. of the basement membrane. Study the lamina densa,
lamina rara externa, and lamina rara interna. What are the
terms used for dense deposits in the A. lamina densa. B.
lamina rara externa, C. lamina rara interna?
Various types of glomerulonephritis are
characterized by one or more of four basic tissue
reactions.
• Hypercellularity is characterized by one or more
combination of the following:
- Cellular proliferation of mesangial or
endothelial cells
- Leukocytic infiltration, consisting of
neutrophils, monocytes and, in some instances,
lymphocytes.
- Formation of crescent by proliferating
parietal epithelial cells.
Robbins 7th Ed, p 967
A glomerulus showing hypercellularity. Identify the component
cells. High power view of encircled area at right. Predict the
effects physiologic effects of this lesion. What are the expected
findings in the urine?
Crescent formation. Black arrow indicates the crescent.
Identify the compressed glomerulus. What cell is proliferating?
If a large percentage of the glomeruli shows this lesion,
predict the pathophysiologic effects.
Various types of glomerulonephritis are
characterized by one or more of four basic tissue
reactions.
2. Basement membrane thickening appears as
thickening of the capillary wall, best seen in
sections stained with periodic acid Schiff (PAS).
This thickening may be due to:
- deposition of amorphous electron dense
material, most often immune complexes on the
endothelial or epithelial side of the basement
membrane or within the GBM itself.
- thickening of the BM proper, as occurs in
diabetes glomerulosclerosis.
Robbins 7th Ed, p 967
Basement membrane thickening in which the capillary
loops are thickened and prominent, but the cellularity is
not increased.
Combined hypercellularity and membranous thickening of
the glomerulus (membrano-proliferative lesion). Identify
the lesion. What cell are proliferating? Predict the
physiologic effects and expected findings in the urine?
Various types of glomerulonephritis are
characterized by one or more of four basic
tissue reactions.
3. Hyalinization and Sclerosis denote the
accumulation of material that is homogeneous
and eosinophilic by light microscopy. By
electron microscopy, the hyalin is extracellular
and consists of amorphous substance, made
up of protein plasma. It is typically the end
result of various forms of glomerular injury. It
can be (1) diffuse, (2) segmental, (3) global,
and (4) mesangial.

Robbins 7th Ed, p 967-968


Segmental glomerulosclerosis. Identify and describe the
area affected. Predict the pathophysiologic effects of this
lesion if diffuse. What are the expected findings in the
urine?
Case No. 1

A 10-year old boy consulted a physician because


of tea colored urine, puffiness of the eyelids noted
especially in the morning, and oliguria. This
symptoms were noticed 3 weeks after he had fever
and sore throat.
Urinalysis showed RBCs and RBC casts, white
blood cells, and proteinuria.
Blood examination showed low complement (C3)
and azotemia.
Describe and classify this lesion according to the light
microscopic basic reactions as shown earlier.
Identify and describe the immune deposits in the supepithelial
region. What are these deposits composed of?
Higher view of subepithelial deposits as indicated by
the arrows. Identify the other components of the
glomerulus.
IF showing deposits of IgG and C3 in the mesangium and
along the basement membrane. Describe the classical
appearance of these deposits?
1. Using the basic principles of immune
reactions to injury, discuss the
probable etiopathogenesis of the
lesion.
2. Make a clinico-pathologic correlation,
including possible outcomes
Case No. 2

A 17-year old female was discovered to have


recurrent microscopic hematuria first discovered
on routine urinalysis during a required physical
examination prior to entry to college. One week
prior to the physical examination, she
experienced a severe upper respiratory tract
infection. No other signs or symptoms were
noted. A renal biopsy was performed.
Identify and describe the glomerular changes, and classify
the lesion according to the light microscopic basic
reactions as shown earlier. The arrow indicates an area
of the mesangium.
Another glomerulus showing more severe changes.
Identify and describe the changes.
PAS stain defining the mesangium. Identify and
describe the lesion.
Study the area of the mesangium and the deposit.
Correlate the changes with the previous slides.
IF studies show immunofluorescence to IgA antibody
but negative to IgG and IgM.
1. Using the basic principles of immune
reactions to injury, discuss the
probable etiopathogenesis of the
lesion.
2. Make a clinico-pathologic correlation,
including possible outcomes
Case No. 3

A 5-year old boy was noticed to have periorbital and


pedal edema for the last 2 months. Urinalysis
showed +++ protein. Blood exam showed 40 g/L
protein and 1.80 mmol/l cholesterol. Renal biopsy
disclosed normocellular glomeruli.
Immunofluorescence studies were negative to all
antibodies.
Transmission electron
microscope (left) and scannic
electron microscope (right)
findings. Identify and describe
the lesion.
1. Using the basic principles of immune
reactions to injury, discuss the
probable etiopathogenesis of the
lesion.
2. Make a clinico-pathologic correlation,
including possible outcomes.
Case No. 4

A 30 year-old male was diagnosed to have


schistosomiasis a year ago. Two months prior
to consultation, he complained of generalized
edema. Urinalysis showed ++++ protein.
Blood examination showed protein – 2.5 /L,
cholesterol – 2.00 mmol/l.
Below are the light microscopic findings: H& E (left), Silver
impregnation (right).
The picture on the left shows the IF findings with IgG; on the
right, the EM findings. Identify and describe the location of the
irregular dense deposit in the EM picture.
1. Using the basic principles of immune
reactions to injury, discuss the
probable etiopathogenesis of the
lesion.
2. Make a clinico-pathologic correlation,
including possible outcomes.
Case No. 5

A 25-year old female consulted a nephrologist


because of blood in the urine (gross hematuria).
P.E. showed a BP of 160/100 and generalized
edema.
Urinalysis showed 3+ protein. Blood chemistry
revealed low protein, high triglycerides and
cholesterol.
Below are the PAS stain (left) and silver stain (right) of the renal
biopsy. Identify, describe, and classify the lesion according to
the basic lesions described earlier.
Identify the electron dense deposits in the subendothelial region
and the splitting of the basement membrane.
1. Using the basic principles of immune
reactions to injury, discuss the
probable etiopathogenesis of the
lesion.
2. Make a clinico-pathologic correlation,
including possible outcomes
Blood is red; urine is yellow.
Nice color combination.

Module edited by ERF, RLM