1. Introduction to Renal Histology Part 2 of 2 Anjali Satoskar MD PhD Department of Pathology anjali.satoskar@osumc.edu

2. Tubules - - Proximal tubule - Loop of Henle - Distal convoluted tubule - Collecting tubule - Collecting duct Tubules

3. Tubules – Modify the glomerular filtrate by reabsorption and secretion (180 liters to 1.5 liters)

4. 95% of the renal cortex is occupied by tubules (proximal tubules)

5. Renal medulla contains only tubules, no glomeruli

6. - Proximal tubule - Loop of Henle - Distal convoluted tubule - Collecting tubule - Collecting duct Tubules

7. PROXIMAL TUBULE Reabsorption S1 and S2 segments –Reabsorb most of NA +, Cl -, K +, H 2 O and most of HC03 - as well as glucose, amino acids. –Luminal brush border and basolateral membrane infoldings, many mitochondria. S3 segment (or pars recta) –Secretion of various ions, drugs, toxins Susceptible to toxic injury. –Less prominent brush border, less mitochondria, little basolateral infoldings.

8. Proximal tubule Metabolically active cells. Tall, lots of cytoplasm. Mitochondria at the base. Brush border at the luminal surface, to increase surface area of absorption.

9. Proximal convoluted tubule – Brush border and basolateral infoldings

10. Histology of proximal tubules, prominent brush border

11. Proximal tubules - Basolateral folds with mitochondria

12. Ultrastructural appearance of proximal tubule

13. Loop of Henle Small flattened cells

14. LOOP OF HENLE Urine concentration (Medullary concentration gradient countercurrent multipliers) Thin descending limb –Simple thin cells, few organelles –Water permeable Thin ascending limb –Simple thin cells, few organelles –Water impermeable Thick ascending limb of Henle (TALH) –Cuboidal cells, basolateral infoldings, mitochondria –Relatively water impermeable –Produces Tamm-Horsfall protein –No brush border

15. Loop of Henle – Maintenance of Medullary concentration gradient

16. Thin loop of Henle Thin limbs of Loop of Henle

17. Thick ascending loop of Henle (secrete Tamm-Horsfall protein)

18. Juxta-glomerular apparatus Tubulo-glomerular feedback

19. Location of the Juxta- glomerular apparatus

20. Juxta-Glomerular Apparatus (JGA) 3 major components:- Juxta-glomerular cells - arterioles Macula densa – distal tubule Lacis cells – mesangial cells

21. Juxta-Glomerular Apparatus (JGA)

23. Function of Juxtaglomerular apparatus Tubuloglomerular feedback Autoregulation – Adjust renal blood flow and the GFR Long term blood pressure control

24. JG apparatus seen in a histologic section

25. Renin granules (electron microscopy)

26. Questions to Review 1. Where is the JGA apparatus located? 2. Renin is secreted by which cells? 3.Proximal tubule brush border serves what purpose? 4. Where does the proximal tubule arise from?

27. Distal tubule

28. DISTAL CONVOLUTED TUBULE Absence of brush border Basolateral infoldings. Similar to TALH Higher N/C ratio than proximal tubular epithelial cells Connecting segment is between the distal convoluted tubule and the cortical collecting duct.

29. Distal convoluted tubules (arrows)

30. Distal convoluted tubule

31. Collecting tubule

32. COLLECTING DUCT Principal cells (2/3 of cells) –Light cells with few organelles –ADH sensitive and role in K+ secretion Intercalated cells (1/3 of cells) –Dark cells –Acid base regulation –Type A: H + secretion –Type B: HCO3 - secretion

33. Type A

34. Type B

35. Medullary collecting ducts COLLECTING DUCT

37. RENAL INTERSTITIUM Extracellular space Peritubular capillaries RELATIVE INTERSTITIAL VOLUME 7% in cortex 10-15% medulla 30-40% deep medulla - papilla

38. Cortex with little interstitium

39. Outer renal medulla with interstitial space between collecting ducts

40. Deep renal medulla with more interstitial space between collecting ducts and loops of Henle

41. FUNCTIONS OF RENAL INTERSTITIUM Tubular oxygen supply Osmoregulation (together with distal tubules) Immune function (interstitial dendritic cells) Some endocrine function (interstitial cells)

42. Renal vasculature Renal artery Segmental arteries Interlobar arteries Arcuate arteries Interlobular arteries Afferent arterioles Glomeruli Efferent arterioles Peritubular capillaries Venules-veins

43. Nephron and the surrounding vascular framework

44. Cross-section of the intra-renal arteries

45. Arteriole

46. Renal oxygen supply is provided by the postglomerular capillaries (peritubular capillaries in the cortex, vasa recta in the medulla)

47. Quiz for revision 1.In which segment of the tubules, does the majority of reabsorption of solutes take place? 2.Aldosterone influences potassium excretion in which segment of the tubules? 3.Where is the renal papilla situated? 4.Where are the slit diaphragms situated?

48. Summary Kidney Glomerulus Tubules Vasculature Interstitium Pair of bean-shaped organs, retroperitoneal. Capsule, cortex, medullary pyramids, calyces, pelvis, ureter. Functional unit - Nephron Glomerular basement membrane structure. Podocytes foot processes, slit diaphragm. Fenestrated endothelium. Glomerular filtration barrier. Proximal, distal, loop of Henle, collecting ducts. Juxta-glomerular apparatus – Autoregulation Renal arteries directly branch from aorta. Elaborate branching pattern in the kidney Surrounds the nephrons and vasculature Less in cortex, more in the medulla. Important in maintenance of osmotic gradient around the loops of Henle. Oxygen supply of tubules – peritubular capillaries

50. Thank you, Any questions? Contact me at: anjali.satoskar@osumc.edu Department of Pathology Division of Renal and Transplant pathology

51. References Basic Histology Lange medical text book Pathologic Basis of Disease Robbins and Cottran

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