The structural and functional unit of kidney, the nephron is highly specialized in view of its function. Here we look at the various histological variations/modification in relation to its function of the Renal Tubule

1. Histological Variation/Modification in
relation to function of the Nephron
Dr. Saran A K
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2.  Nephron
 Tubular Segments
Common Histological Features
Histological Features
• 1. Renal Corpuscle
• 2. Proximal Convoluted Tubule
• 3. Loop of Henle
• 4. Distal Convoluted Tubule
• 5. Collecting Duct
 Applied Aspects
 References
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3. • The nephron is the structural and
functional unit of the kidney.
• Each kidney contains approximately
1.3 million nephrons.
• The nephron consists of the
• Renal corpuscle
• Glomerulus
• Bowman’s Capsule
• Tubule system
Coronal Section Through a Unipapillary Kidney
Fig 1.1 Comprehensive Clinical Nephrology
3

4. Nephron Divisions Length
Bowman’s Capsule
Proximal Tubule
PCT and PST(pars recta)
15 mm, 55µm in diameter
Loop of Henle
Descending Thin Segment
Ascending Thin Segment
Thick Ascending Limb
Length variable up to 25mm
Cortical Nephrons
Juxta Medullary (15%)
Distal Convoluted Tubule 5 mm
Collecting Duct
Cortical Collecting Duct
Medullary Collecting Duct
20 mm
45-65 mm (Total Length)
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5. General Histological Features
1. Single-layer epithelium
2. Basolateral Membrane invaginated to form
basal spaces
3. Cytoplasmic processes from lateral and
basal surfaces of the cells interdigitate
with the similar processes of adjacent cells,
forming Lateral Intercellular space.
Lateral space continuous with peritubular space
functionally
Diagram of a Juxtamedullary Nephron
Fig 38-1 Ganong’s Review of Medical Physiology 26th Edition
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6. 2. Tight Junctions
• Adjacent cells united by apical tight
junctions consisting of a tight
junction (zonula occludens), an adherens
junction, and, rarely, a desmosome
• Leaky tight junctions
• Tight tight junctions
Fig 38-8 Ganong’s Review of Medical Physiology 26th Edition
Peritubular
Space
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7. 1. Paracellular transport : depends
on the type of tight junction
2. Transcellular transport depends
on specific channels, carriers, and
transporters included in the apical and
basolateral cell membranes.
Figure 1.10. Tubular epithelia
Comprehensive Clinical Nephrology
Transport Systems
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8. • Glomerulus
• Capillary Endothelium (E)
• Bowman’s Capsule
• Parietal Layer (PE)
• Visceral Layer
• Podocytes (PO)
• Glomerular Membrane
Renal Corpuscle
Figure 1.4. Comprehensive Clinical Nephrology
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1. Renal Corpuscle

9. Glomerular Membrane/ Filtration Barrier
1. Glomerular Endothelium :
numerous fenestrae - pore size
70-90 nm
2. Glomerular Basement Membrane
(GBM): acts as a physical barrier
and an ion-selective filter
3. Visceral layer of Bowman’s
capsule: podocytes -foot processes
or pedicels. Slits closed by
filtration slit diaphragm acts as a
size-selective filter.
Three Layers of Filtration Barrier
Fig 22.13 Medical Physiology Rhodes and Rhotney 4th Edition
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10. Scanning Electron Micrograph of a Glomerulus EM of Glomerular Capillary and Podocyte
Fig 20.12, Fig 20.13 Histology A Text and Atlas, Michael H Ross
GM permits the free passage of neutral substances up to 4nm in diameter
and almost totally excludes those with diameters greater than 8nm.
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11. • Mesangial Cells
• Intra glomerular
• Structural Support
• Regulate Blood Flow
• Phagocytic Activity
• Extra glomerular (lacis cells)
• Juxtaglomerular Cells
• Macula Densa
Juxta Glomerular Apparatus
• feedback control of GFR and
Blood flow in same nephron
Structure of Renal Corpuscle
Fig 20.7 Histology A Text and Atlas, Michael H Ross
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12. 2. Proximal Convoluted Tubule
• The epithelial cells are cuboidal in
shape
• A layer of closely packed microvilli
covers the luminal surface forming a
brush border
• The cells have prominent basal and
lateral processes and interdigitate
extensively
Drawing of proximal convoluted tubule cells
Fig 20.17 Histology A Text and Atlas, Michael H Ross
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13. Electron Micrograph of Proximal Tubule Cell
Fig 20.18 Histology A Text and Atlas, Michael H Ross
• Prominent Gogli Apparatus with ER
and vacolues for synthesizing
membrane components, sorting and
targeting them to surface sites
• Numerous mitochondria
concentrated in the basal processes
created by the invagination of basal
membrane.
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14. Cellular Ultrastructure and Primary Transport in PCT
Fig 27-6 Guyton and Hall Medical Physiology
• Glucose, Sodium Chloride and Sodium
Bicarbonate actively absorbed
• Transporters present in plasmalemma
membrane (SGLT1 and NHE3)
• Na+-K+-ATPase in basolateral membrane
• Abundant mitochondria supplies energy
• Water : 66% of all the water absorption
• well adapted for the processes of
reabsorption and secretion brush border
and basal processes
• Aquaporin1 abundance (Obligatory)
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15. • Proteins and large peptides are
endocytosed
• Prominent Endosomal-Lysosomal system
present towards the apex
• Organic acids and bases, such as drugs and
drug metabolites are secreted.
Figure 1.11. PCT
Comprehensive Clinical Nephrology
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16. • Consist of the Thin Descending Limb and the Thick Ascending Limb
• Long Looped Nephrons have a Thin Ascending Limb
• The Thin Descending Limb is permeable to water and few solutes while the
Thick Ascending Limb is impermeable to water but not to solutes.
3. Loop of Henle
Thin Descending Limb Thick Ascending Limb
• 2-14mm,30 µ • 12mm, 60µ
• Flat squamous cell
• Leaky Tight Junctions
• Cuboidal cell
• Tight Tight Junctions
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17. Thin Descending Limb Thick Ascending Limb
• Few mitochondria • Large number of mitochondria
• Poorly developed luminal and
basolateral surface
• Extensive invagination of basal
membrane
• Passive Diffusion of Substances
• Water 15-20%
• Active Reabsorption
• Na+-K+-2Cl- Co-transporter
• Na+-H+ Counter transport
• Na+-K+ ATPase
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18. • Thin Descending Limb helps in the absorption of
water and increases tubular fluid osmolality
• Leaky Tight Junctions
• low level of metabolic activity
• designed for the passive diffusion of water
and urea
• Thick Ascending Limb forms Diluting Segment of
the kidney along with DCT
• Impermeable to water (tight tight junctions)
• Metabolically active and designed to perform
active reabsorption of solutes
Cellular Ultrastructure and Primary Transport in LoH
Fig 27-8 Guyton and Hall Medical Physiology
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19. Distal Nephron
• Made up of
• Distal Convoluted Tubule
• Connecting Tubule
• The Collecting Duct
• The junction between the cortical thick ascending limb and the distal nephron
contains JG Apparatus
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20. 4. Distal Convoluted Tubule
Electron Microscope of a Distal Convoluted Tubule Cell
Fig 20.18 Histology A Text and Atlas, Michael H Ross
• Cuboidal Epithelium
• Extensive basal and lateral IP
• Greatest numerical density of Mitochondria
• Lack a brush border but has Microvilli
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21. • Reabsorption of Na
• Early DCT: Transporters present in plasmalemma
membrane (Na+-Cl- Co transporter)
• Late DCT: ENaC (P Cells)
• Regulated by Aldosterone – Na+ Balance
• Na+-K+-ATPase in basolateral membrane
• Abundant Mitochondria
• 5% filtered water reabsorbed
• Early DCT : impermeable
• Late DCT : Controlled by ADH ( V2 Receptors and
Aquaporin 2 in P Cells) and by Na+ absorption by
aldosterone
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Cellular Ultrastructure and Primary Transport DCT
Fig 27-9Guyton and Hall Medical Physiology

22. 5. Collecting Duct
• Collecting Duct is divided into
• Cortical Collecting Duct
• Medullary Collecting Duct
• Cells appear like in DCT but taller and
more granular
• Contains two distinct type of cells
• Principal Cells (P)
• Intercalated Cells (I)
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23. Principal (P) or the Light Cells Intercalated (I) or Dark Cells
• More in number • Less in number
• Relative paucity of cell organelles • Abundant mitochondria
• Basally located interdigitations with
neighboring cells.
• Few short microvilli • Have more microvilli
• Numerous vesicles are present in the
apical cytoplasm
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24. • Water Reabsorption : Fine Control of Urine Conc.
• 8-10%
• P Cell
• Antidiuretic hormone (ADH) acts on V2R
• aquaporin-2 (AQP-2) to luminal surface,
AQP3 and AQP4 to interstitium
• Facultative Reabsorption
• Sodium Reabsorption and Potassium Secretion
• P Cells
• through ENaC
• ENaC respond to Aldosterone - RAAS
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Cortical Collecting Duct

25. • Secretion of H+ : Acidification of Urine
• The intercalated cells are involved in the
Reabsorption of HCO3
- with concomitant
secretion of H+ leading to further
acidification in Late DCT and CD
• In Acidosis number of H+ pumps increases
by insertion of the tubulovesicles into
apical cell membrane
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Primary Active Secretion of H+ Intercalated Cells
(Late DCT and CD)
Fig 30-6 Guyton and Hall Medical Physiology

26. • Urea Transport : Concentrating Mechanism
• The terminal portions of CD express the
urea transport system (UTB1) - recycling
of Urea
• H+-ATPase Transporter
• H2O Reabsorption depending on the level of
ADH
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Medullary Collecting Duct
Cellular Ultrastructure and Primary Transport Medullary CD
Fig 27-13 Guyton and Hall Medical Physiology

27. • Filtration Membrane
1. Alport’s syndrome (Hereditary Glomerulonephritis)
Mutation in 5th chain of type IV collagen
2. Autoimmune response to 3rd chain of type IV collagen Goodpasture
syndrome
• Mesangial Cells
1. IgA nephropathy (Berger disease)
2. Diabetic Nephropathy
Applied Aspects
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28. • Diabetes Insipidus
1. Central Diabetes Insipidus (CDI)
2. Nephrogenic Diabetes Insipidus defective AQP-2 and ADH receptor proteins
• Diuretics
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Type Action Examples
Loop Diuretics Inhibit Na+-K+-2Cl- in Thick
Ascending Limb of LoH
Furosemide
Thiazide Diuretics Inhibit Na+Cl- symporter in DCT Chlorothiazide
K+ Sparing Diuretics
• Aldosterone antagonist
• Direct ENaC Blocker
Inhibit ENaC in late DCT and
Cortical CD
Spironolactone
Amiloride
Carbonic Anhydrase Inhibitor Prevent HCO3
- Reabsorption in PCT
and secretion of H+
Na+-H+ Antiport blocked
Acetazolamide
Dorzolamide
Osmotic Diuretics Increases fluid osmolality LoH Mannitol

29. 29
• Renal Tubular Syndromes
1. Fanconi Syndrome : Generalized reabsorption defect in PCT
2. Bartter Syndrome : Reabsorption Defect in Thick Ascending Loop of
Henle Na+-K+-2Cl- Co-transporter (mimics Loop Diuretic)
3. Gitelman Syndrome : Reabsorption Defect of NaCl in DCT (mimics
thiazide Diuretic)
4. Liddle Syndrome : Gain of function mutation of ENaC Channels in
Collecting Tubule

30. 30

31. References
1. Ganong. Review of Medical Physiology 22nd Edition McGraw Hill
2. Best and Taylor’s Physiological Basis of Medical Practice 12th Edition
Williams & Wilkins
3. Michael H Ross. Histology : A Text and Atlas 6th Edition Williams & Wilkins
4. Samson Wright’s Applied Physiology 13th Edition Oxford University Press
5. Guyton & Hall. Textbook of Medical Physiology 11th Edition Saunders
Elsevier
6. Ganong. Review of Medical Physiology 26th Edition McGraw Hill
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32. Thank You!
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