Renal Pathology Tutorial

Written by: J. Charles Jennette, MD
Produced by: F.W. Maddux, MD
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Normal Kidney Histology

The normal renal cortex contains glomeruli, other vessels, tubules and interstitium. When evaluating a renal specimen by light microscopy on an H&E stained section,(slide 1) the following glomerular features should be evaluated: the overall cellularity of the glomerulus, the symmetry of the glomerulus (which of course is broken at the hilum if there is a section through it) and the thickness of the capillary walls. Normally, all the glomerular capillaries should be about the same thickness, which is very thin (almost wispy). With normal cellularity, cell nuclei are not clustered or overlapping. Clusters of cells, especially away from the hilum, indicate abnormal hypercellularity. Increased cells within the lumens of capillaries indicate leukocyte infiltration or, rarely, an angiotrophic lymphoma. In the cortex but not the medulla, the tubules should be almost back to back, i.e. the tubular basement membranes should be almost touching. There is very little interstitium in the cortex, therefore, if there is space between the tubules, there is something wrong in the tubulointerstitial compartment (e.g. edema or fibrosis). Intrarenal arteries have very little intima, i.e. there is little or no space between the endothelium and the muscularis. Pathologic processes expand the arterial intima, e.g. collagen in arteriosclerosis and proteinaceous insudate in an acute thrombotic microangiopathy.

In the glomerular diagram in slide 2, the different colors indicate the various cell types that are of interest in assessing the pathologic changes that occur in a glomerulus (green = epithelial cells, yellow = endothelial cells, red = mesangial cells). Visceral epithelial cells line the capillary walls. Parietal epithelial cells line Bowman's capsule, and are continuous with the proximal tubular epithelial cells. Endothelial cells line capillary lumens. Mesangial cells are in the middle (meso) between the capillaries (angis). The mesangial cells are modified smooth muscle cells that are continuous with the vascular smooth muscle cells in the hilar arterioles. As such, they have a contractile capability and can tug on the edges of the capillaries and thus control blood flow through the glomerulus. Mesangial cells also produce a variety of cytokines when stimulated, and are capable of phagocytosis. There is a route for trafficking of debris through the mesangium that begins in the subendothelial zone and enters the mesangium and then passes through physiologic if not actual channels through the matrix to the hilum.

Slide 3 shows special stains that often are used in evaluating renal biopsy specimensIfrom left to right: PAS,trichrome, H&E, Jones silver stains). Many laboratories use a battery of stains for evaluating renal disease, e.g., H&E, PAS, trichrome, and silver stains. The silver stain accentuates collagenous structures, e.g., in the glomerulus, the mesangial matrix and the glomerular basement membrane. The PAS stain also accentuates matrix and basement membrane constituents, as does the blue or green component on the trichrome stain. In certain circumstances the trichrome stain demonstrates immune deposits as fuchsinophilic (red) structures.

Slide 4 is a diagram of a single glomerular capillary and illustrates the ultrastructural features that are assessed when evaluating renal biopsy specimens. The peripheral endothelial cell cytoplasm, which has pores through it, looks like a little string of sausages on cross section. This allows recognition of the lumenal side of the capillary wall. The visceral epithelial cells, or podocytes, have foot processes that are intact in normal glomeruli and often effaced in proteinuric conditions. The glomerular basement membrane has 3 ultrastructural zones that can be disturbed in various glomerular diseases: the lamina densa in the middle, the lamina lucida (rara) externa and the lamina lucida (rara) interna. The glomerular basement membrane does not completely enclose the lumen, unlike the endothelial basement membrance in most vessels, but rather splays out over the mesangium to become the paramesangial basement membrane. This leaves a functional gap where materials from the capillary lumen or subendothelial zone (having passed through the endothelial pores) can directly enter the mesangium without traversing the basement membrane. This explains why the mesangium is a preferential sequestration point for some types of debris, including immune complexes.

Slide 5 is an electron micrograph that shows a portion of 1 capillary loop with adjacent mesangium. The endothelial cell nucleus sits over the origin of the mesangium, which is where it is usually found. A few pores through the endothelial cytoplasm can be seen. The glomerular basement membrane lamina lucida externa is the thin lucent zone just under the foot processes of the visceral epithelial cell. The bulk of the basement membrane is the lamina densa.

Slide 6 is a much higher magnification electron micrograph. The urinary space and the foot processes are at the top. Slit pore diaphragms connect the epithelial cell foot processes. The pores through the endothelial cell are below the basement membrane. The thickness of the glomerular basement membrane lamina densa is about 5-6 times thicker than the lamina lucida externa in this particular electron micrograph. The lamina lucida externa thickness is a useful landmark that can be used to assess the normal thickness of the glomerular basement membrane. The thickness of the lamina densa is important in making the diagnosis, for example, of thin basement membrane nephropathy and diabetic glomerulosclerosis. Another internal reference point for basement membrane thickness is an intact foot process. If you average the width of intact foot processes and then turn that 90 degrees, that is about the normal thickness of the laminar densa. Therefore, if you compare the thickness of the lamina densa to that of the lamina lucida externa or to an intact foot process, you can determine whether the basement membrane is normal or abnormal thickness.


[Renal Pathology Tutorial Home Page]
[Normal Histology] [Clinical Presentation] [Nephrotic Syndrome] [Minimal Change]
[Membranous] [FSGS] [Type I MPGN] [Type II MPGN]