1. Pathology of the Urinary System Lecture-2

2. Recap.. Anatomy and physiology of kidney Structure of nephron and components Functional aspects Clinical aspects Pathogenesis

3. Recap.. Glomerular basement membrane: 320 nm thick in adults Central lamina densa Lamina rara on either side. Contains in addition to IV collagen and other components, polyanionic proteoglycans. Plays a very important role in charge dependant filtration. Does not allow anions (proteins) but allows water and cations

4. Recap.. Filtration barrier of glomerulus: Fenestrated endothelial cells (70-100 nm) Glomerular basement membrane Filtration slits of podocyte (20-30 nm) Size dependant and charge dependant filtration. Allows particles below 3.5 nm to pass. Restricts albumin (3.6 nm) and other proteins.

5. Recap.. Juxta-glomerular apparatus: JG cells of afferent arteriole Macula densa of DCT Lacis cells of mesangium Important source of renin Plays a role in hypertension

6. Clinical syndromes related to renal disease

7. Chr renal failure Ac renal failure Nephrotic synd Acute nephritis Clinical syndromes related to renal disease

8. Chr renal failure Ac renal failure Nephrotic synd Acute nephritis Clinical syndromes related to renal disease Hematuria, proteinuria, hypertension

9. Chr renal failure Ac renal failure Nephrotic synd Acute nephritis Clinical syndromes related to renal disease Hematuria, proteinuria, hypertension Proteinuria > 3.5 g/day, hypoalbuminemia <2 g/dl, edema, hyperlipidemia, lipiduria

10. UremiaChr renal failure Oliguria / anuria, azotemia, (Anuria <100 ml; oliguria 100-400 ml) Ac renal failure Proteinuria > 3.5 g/day, hypoalbuminemia <2 g/dl, edema, hyperlipidemia, lipiduria Nephrotic synd Hematuria, proteinuria, hypertensionAcute nephritis Clinical syndromes related to renal disease

12. Pathogenesis of Glomerulonephritis

13. Pathogenesis of glomerulonephritis Immune mechanisms underlie majority of the primary glomerulonephritis 1. In situ immune complex deposition a. Intrinsic (fixed) glomerular antigens Anti GBM, Heymann nephritis, membranous nephropathy b. Planted antigens (proteins, bacterial, viral) 2. Circulating immune complexes Others: cytotoxic antibodies, chemical mediators, cell mediated injury, non-immune mechanisms.

17. Glomerular response to injury Glomerulus responds to a variety of injuries in a very limited manner Hypercellularity - mesangial, endocapillary, extracapillary (crescents), exudation Basement membrane changes Sclerosis Others - Necrosis, deposits of fibrin, abnormal proteins, etc.

20. Diffuse: All glomeruli in the biopsy / kidney are affected Focal: Only few glomeruli are affected (<50%) Global: The entire glomerulus is involved Segmental: Only part of the glomerulus (few tufts) are involved Terminology

21. Diffuse changes

22. Focal changes

23. Global changes

24. Segmental changes Less than 80% of glomerular surface is involved