Renal Corpuscle & Glomerular Filtration Barrier

Structural Overview of the Renal Corpuscle

• The renal corpuscle = glomerulus (capillary tuft) + Bowman's capsule.
• Capillaries are fenestrated:
  • Endothelial cells possess large fenestrations (openings) without diaphragms.
  • Fenestrations speed transfer of plasma while retaining formed elements (RBCs, WBCs, platelets).
• Bowman's capsule encases the capillaries and creates Bowman’s (urinary) space – the first location of the ultrafiltrate.

Layers and Cells of Bowman's Capsule

• Two concentric layers:
  • Parietal layer
  • Simple squamous epithelium.
  • Forms the outer wall; nuclei appear flattened on light microscopy.
  • Visceral layer
  • Highly specialized epithelial cells = podocytes.
  • Directly apposed to glomerular capillaries.
• Three cell types present in the glomerulus
  • Fenestrated endothelial cells (capillary wall).
  • Podocytes (visceral epithelial cells).
  • Intraglomerular mesangial cells (within interstitial connective tissue between capillary loops).

Podocyte Architecture

• Cell body gives rise to:
  • Primary processes → elongate around capillaries.
  • Foot processes (pedicels) – secondary projections that interdigitate with pedicels of neighboring podocytes.
• Spaces between pedicels = filtration slits (≈ 25{-}30\,\text{nm} wide).
• A thin, zipper-like slit diaphragm bridges each filtration slit.
  • Major protein: nephrin (anchored to actin cytoskeleton via podocin, CD2AP, etc.).
  • Provides size-selective and charge-selective filtration.

Glomerular Basement Membrane (GBM)

• Fused basal laminae of capillary endothelium & podocytes.
• Tripartite ultrastructure (EM):
  • Inner lamina rara (lucida) interna – adjacent to endothelium.
  • Middle lamina densa – electron-dense, thick.
  • Outer lamina rara (lucida) externa – adjacent to podocytes.
• Principal molecular components
  • Type IV collagen → meshwork forming physical sieve.
  • Heparan sulfate proteoglycans (e.g., perlecan) → impart strong negative charge, repel anionic plasma proteins.
  • Laminin & fibronectin → adhesive glycoproteins anchoring cells to GBM.

Filtration Barrier: Route of Ultrafiltrate

1. Capillary lumen → passes through endothelial fenestrations.
2. Crosses GBM (lamina rara interna → lamina densa → lamina rara externa).
3. Traverses filtration slit diaphragm between podocyte pedicels.
4. Enters Bowman’s space → flows into proximal convoluted tubule (PCT).

Functional Poles of the Corpuscle

• Vascular pole
  • Site where afferent arteriole enters & efferent arteriole exits.
  • Mesangial cells cluster here; juxtaglomerular apparatus situated nearby.
• Urinary pole
  • Opposite side; continuous with lumen of the PCT where ultrafiltrate drains.

Mesangial Cells

• Location: between capillary loops, enclosed by glomerular basement material.
• Functions
  • Phagocytosis: remove debris trapped in GBM, keep filter patent.
  • Structural support for capillaries.
  • Secrete ECM, cytokines, prostaglandins; modulate glomerular blood flow via contractile filaments.

Quantitative & Physiological Highlights

• Renal blood flow filtered daily ≈ 180\ \text{L} plasma → ultrafiltrate.
• Vast majority (>99\%) reabsorbed along nephron (mainly PCT), returning water, Na$^+$, K$^+$, glucose, amino acids, etc.
• Counter-current multiplier in Loop of Henle & exchanger in vasa recta fine-tune osmotic gradients for water reabsorption.
• Final urine concentration regulated in collecting ducts under ADH influence.

Microscopic Identification Tips

• Light Microscopy (H&E)
  • Glomerulus appears as a round tuft; Bowman’s space a clear halo.
  • Parietal layer nuclei = flattened; visceral layer nuclei harder to discern.
  • PCTs surround corpuscles; look acidophilic, have brush border, irregular “star-shaped” lumen.
• Electron Microscopy
  • Endothelial fenestrations visible (~70{-}90\,\text{nm}).
  • GBM shows three distinct electron densities.
  • Interdigitating pedicels produce slit pores; diaphragms appear as thin dense lines with central pores.

Clinical & Pathological Correlations

• Glomerulonephritis / Nephritic syndromes
  • Immune complex or anti-GBM antibody deposition in specific GBM zones (subendothelial vs subepithelial) used for classification.
• Minimal-change disease
  • Effacement (fusion) of podocyte foot processes → massive proteinuria with normal LM appearance.
• Heparan sulfate loss (e.g., diabetes) reduces negative charge → albumin leakage (albuminuria).
• Podocyte injury via infection, toxins, or autoimmunity compromises slit diaphragms → nephrotic syndrome.

Ethical / Practical Implications

• Understanding molecular composition of GBM and slit diaphragm has led to genetic testing for congenital nephrotic syndromes (mutations in nephrin, podocin).
• Targeting mesangial proliferation & immune deposition is central to emerging renal therapeutics.