Cdsa Genito Urinary Tract Final

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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 Kidney

Urine

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

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