Functional anatomy of glomerulus and tubules

1. FUNCTIONAL ANATOMY OF
GLOMERULUS AND TUBULES
Presenter – Prem Mohan Jha

2. Development Of Urogenital System
• Verterate kidney is derived from The Intermediate
Mesoderm of the Urogenital Ridge, found in posterior
wall of abomen in the developing fetus.
• Develops in 3 successive stages-
– Pronephros
– Mesonephros
– Metanephros
• Only the METANEPHROS gives rise to definitine adult
kidney.

3. Gross Features Of Kidney
• Paired
• 11 cm x 6 cm x 2.5 cm
• Retroperitoneal
• Between T12 and L3
• Left kidney higher than the
right
• Weight :
– 125 to 170 gm in adult
male
– 115 to 155 gram in adult
female
• On MRI , normal refference
values(mean+-2SD)
– For length
• Male – 10.7 to 14.3
cm
• Female – 9.5 to 13.9
cm
– For Volumes
• Male – 132 to 276 ml
• Female – 87 to 223 ml

4. Outer Kidney Anatomy
Layers of supportive tissue
• Renal fascia
– The anchoring outer
layer of dense fibrous
connective tissue
• Perirenal fat capsule
– A fatty cushion
• Fibrous capsule
– Prevents spread of
infection to kidney

5. Internal Anatomy
• Renal cortex (Thickness – 1 cm)
– A granular, superficial, pale, outer region
• Renal medulla
– Darker, inner, cone-shaped medullary (renal) pyramids (8 –
18) separated by renal columns
• Lobe
– A medullary pyramid and its surrounding cortical tissue
• Papilla
– Tip of pyramid; releases urine into minor calyx

6. Internal Anatomy
• Renal pelvis
– The funnel-shaped tube within the renal sinus
• Major calyces
– The branching channels of the renal pelvis that
• Collect urine from minor calyces
• Empty urine into the pelvis
• Urine flows from the pelvis to ureter
– Ureters originate from the lower portion of renal pelvis at
uretero-pelvic junction.
– Descend 28 to 34 cm to open into fundus of the bladder
– Mean size of the ureters in adults is 1.8cm, with maximum
width of 3.0 cm is considered to be normal.

7. Renal cortex
Renal medulla
Major calyx
Papilla of
pyramid
Renal pelvis
Ureter
Minor calyx
Renal column
Renal pyramid
in renal medulla
Fibrous capsule
Renal
hilum
Photograph of right kidney, frontal section
(Diagrammatic view

8. Blood and Nerve Supply
• Renal arteries deliver 25% (1200 ml) of cardiac output to the
kidneys each minute
• Arterial flow into and venous flow out of the kidneys follow
similar paths
• Lymphatic Drainage:
– The lymph vessels follow the arteries. Lymph drains to the lateral
aortic lymph nodes around the origin of the renal artery.
• Nerve supply
– The nerve supply is the renal sympathetic plexus. The afferent fibers
that travel through the renal plexus enter the spinal cord in the 10th,
11th, and 12th thoracic nerves

9. Aorta
Renal artery
Segmental artery
Interlobar artery
Arcuate artery
Cortical radiate artery
Afferent arteriole
Glomerulus (capillaries)
Inferior vena cava
Renal vein
Interlobar vein
Arcuate vein
Cortical radiate
vein
Peritubular
capillaries
and vasa recta
Efferent arteriole

10. Nephrons
• Structural and functional units that form urine
• 1 to 3 millions per kidney
• Two main parts
1. Glomerulus (renal corpuscle)
– A tuft of capillaries
2. Renal tubule
– Begins as cup-shaped glomerular (Bowman’s)
capsule surrounding the glomerulus
• Cortical nephrons— 80%
• Juxtamedullary nephrons- 20%

12. Glomerular Basement Membrane
• Skeleton of glomerular tuft
• Trilaminar structre
– Lamina desa
– Lamina rara interna
– Lamina rara externa
• Outer aspect : completely
covered with podocytes
• Interior : filled with
capillaries and mesangium
• Components
– Type 4 collagen : major
component
– Laminin
– Heparan sulphate
proteoglycans
– Others
• Type 5 & 6 collagen
• Nidogen (entactin)

13. • Mature GBM consists of type 4 collagen made of alfa-3,4,5 chains ,
instead of alfa 1 &2 chains of most of other membranes.
• Laminin 11 is made of : alfa5, beta2 & gamma1 chains.
• Type 4 collagen is the antigenic target in Goodpasture Disease.
• Mutations in the genes of alfa 3,4,5 chains of type 4 collagen are
responsible for Alport Syndrome
• Three dimensional network of type 4 collagen/ triple helix that is
400nm in length
• Negatively charged because of polyanionic proteoglycans like
heparan sulphateproteoglycans includind perlecan and agrin

14. Mesangium
• 3 major cell types occur
within glomerular tuft
– Mesangial cells
– Endothelial cells
– Podocytes
• Mesangial/Endothelial/Pod
ocyte Cell Ratio -- 2 : 3 : 1
• Glomerular mesangium
– Mesangial cells
– Mesangial matrix

15. • Mesangial cells
– Irregular
– Possess receptors for
• Angiotensin 2
• Vasopressin
• Atrial natriuretic
factor
• Transforming growth
beta
• Others : PDGF, EGF,
CTGF
• Mesangial matrix
– Anchor mesangial cells
to gbm
– Components
• Collagen type – 4/ 5/
6
• Fibrillin
• Glycoproteins
(fibronectin is most
abundant)
• Several types of
proteoglycans

16. • Endothelium
– Consists of cell bodies
and cytoplasmic sheets
– Glomerular endothelial
pores lake diaphragm
– Pore size : 50 – 100 nm
– Negatively charged
• Parietal epithelium
– Consists of squamous
cells resting on
basement membrane
– Predominent
proteoglycan is
chondroitin sulphate

17. Visceral Epithelium
• Also known as PODOCYTES
• Highly differentiated cells
• Unable to replicate therefore degenerated podocytes can not
be replaced in adults
• Most specific structural feature of podocytes : pattern of foot
processes covering the outer aspect of glomerular capillaries
• Form the filtration slit or slit diaphragm

18. Filtration Barrier
• Endothelial Pores, GBM, Slit
Diaphragm
• Quite permeable to water, small
solutes, ions
• Barrier function is selective For
Size, Shape And Charge
• Uncharged macromolecules upto
an effective radius of 1.8 nm pass
freely through the filter
• Totally restricted at an effective
radii of more than 4 nm
• Plasma Albumin has an effective
radium of 3.6 nm

19. Nephron Capillary Beds
1. Glomerulus
– Afferent arteriole  glomerulus  efferent arteriole
– Specialized for filtration
– Blood pressure is high because
• Afferent arterioles are smaller in diameter than efferent
arterioles
• Arterioles are high-resistance vessels
2. Peritubular capillaries
– Low-pressure, porous capillaries adapted for absorption
– Arise from efferent arterioles
– Cling to adjacent renal tubules in cortex
– Empty into venules
3. Vasa recta
– Long vessels parallel to long loops of Henle
– Arise from efferent arterioles of juxtamedullary nephrons
– Function information of concentrated urine

20. Cortical nephron
• Has short loop of Henle and glomerulus
further from the corticomedullary junction
• Efferent arteriole supplies peritubular
capillaries
Juxtamedullary nephron
• Has long loop of Henle and glomerulus
closer to the corticomedullary junction
• Efferent arteriole supplies vasa recta
Corticomedullary
junction
Cortical radiate vein
Cortical radiate artery
Afferent arteriole
Afferent arteriole
Collecting duct
Distal convoluted tubule
Efferent arteriole
Vasa recta
Loop of Henle
Arcuate artery
Arcuate vein
Peritubular capillaries
Glomerular capillaries
(glomerulus)
Glomerular
(Bowman’s) capsule
Renal
corpuscle
Ascending or thick limb
of the loop of Henle
Descending
or thin limb of
loop of Henle
Efferent arteriole
Proximal
convoluted tubule

21. Renal Tubule
• Loop of Henle
– with descending and ascending limbs
– Thin segment usually in
descending limb
– Simple squamous
epithelium
– Freely permeable to water
– Thick segment of ascending limb
• Cuboidal to columnar cells
• Distal convoluted tubule (DCT)
– Cuboidal cells with very few
microvilli
– Function more in secretion than
reabsorption
– Confined to the cortex
Subdivided into
•Proximal tubule
•Intermediate tubule
•Distal tubule
•Connecting tubule
•Collecting duct

22. Proximal Tubule
• Reabsorb bulk of filtered water and solutes
• Prominent brush border
• Basolateral cell membrane : Na-K-ATPase
• Luminal cell membrane : Na+ /H+ exchanger
• Aquaporin 1
• Reabsorption of polypeptides, proteins such as albumin
• 3 segments – s1, s2, s3 or P1, P2, P3

23. Loop Of Henle
• Straight portions of proximal
tubule/ thick descending limb
• Thin descending limb –
– Highly permeable to water
due to AQP1
• Thin ascending limb
– Impermeable to water
• Thick ascending limb
– Diluting segnment
– Reabsorb NaCl
• Function
– Generate medullary osmotic
gradient
– Salt is trapped in medulla &
water is carried to cortex
which may return to systemic
circulation
– Na/K/2Cl cotransporter
– Tamm Horsfall protein
• Prevent stone formation
• Contain Macula Densa

24. Distal Convoluted Tubule
• Most extensive interdigitation of cells
• Greatest density of mitochondria
• Numerous microvilli
• Luminal Na-Cl cotransporter
• Target of thiazide diuretics

25. Collecting Ducts
• Receive filtrate from many nephrons
• Fuse together to deliver urine through papillae into minor
calyces
• Cell types
– Intercalated cells
• Cuboidal cells with microvilli
• Function in maintaining the acid-base balance of the
body
– Principal cells
• Cuboidal cells without microvilli
• Help maintain the body’s water and salt balance

26. Fenestrated
endothelium
of the glomerulus
Microvilli
Cortex
Medulla
Podocyte
Basement
membrane
Mitochondria
Highly infolded plasma
membrane
Proximal
convoluted
tubule
Distal
convoluted
tubule
• Descending limb
Loop of Henle
• Ascending limb
• Glomerular capsule
Renal corpuscle
• Glomerulus
Thick segment
Collecting
duct
Intercalated cell
Principal cell
Thin segment
Proximal convoluted tubule cells
Glomerular capsule: parietal layer
Glomerular capsule: visceral layer
Distal convoluted tubule cells
Loop of Henle (thin-segment) cells
Collecting duct cells
Renal cortex
Renal medulla
Renal pelvis
Ureter
Kidney

27. Cortical nephron
• Has short loop of Henle and glomerulus
further from the corticomedullary junction
• Efferent arteriole supplies peritubular
capillaries
Juxtamedullary nephron
• Has long loop of Henle and glomerulus
closer to the corticomedullary junction
• Efferent arteriole supplies vasa recta
Corticomedullary
junction
Ureter
Renal pelvis
Kidney
Cortex
Medulla
Cortical radiate vein
Cortical radiate artery
Afferent arteriole
Afferent arteriole
Collecting duct
Distal convoluted tubule
Efferent arteriole
Vasa recta
Loop of Henle
Arcuate artery
Arcuate vein
Peritubular capillaries
Glomerular capillaries
(glomerulus)
Glomerular
(Bowman’s) capsule
Renal
corpuscle
Ascending or thick limb
of the loop of Henle
Descending
or thin limb of
loop of Henle
Efferent arteriole
Proximal
convoluted tubule

28. Juxtaglomerular Apparatus (JGA)
• One per nephron
• Important in regulation of filtrate formation and blood
pressure
• Involves modified portions of the
– Distal portion of the ascending limb of the loop of Henle
– Afferent (sometimes efferent) arteriole
• Granular cells (juxtaglomerular, or JG cells)
– Enlarged, smooth muscle cells of arteriole
– Secretory granules contain renin
– Act as mechanoreceptors that sense blood pressure

29. Juxtaglomerular Apparatus (JGA)
• Macula densa
– Tall, closely packed cells of the ascending limb
– Act as chemoreceptors that sense NaCl content of filtrate
• Extraglomerular mesangial cells
– Interconnected with gap junctions
– May pass signals between macula densa and granular cells

30. Glomerulus
Glomerular capsule
Afferent
arteriole
Efferent
arteriole
Red blood cell
Podocyte cell
body (visceral
layer)
Foot processes
of podocytesParietal layer
of glomerular
capsule
Proximal
tubule cell
Lumens of
glomerular
capillaries
Endothelial cell
of glomerular
capillary
Efferent
arteriole
• Macula densa cells
of the ascending limb
of loop of Henle
• Granular cells
• Extraglomerular
mesangial cells
Afferent arteriole
Capsular
space
Renal corpuscleJuxtaglomerular
apparatus
Mesangial cells
between capillaries
Juxtaglomerular
apparatus

31. THANK YOU