Renal Anatomy and Physiology
Transcript of Renal Anatomy and Physiology
Renal Anatomy
Rosella N. Blancas, M.D.
Renal Anatomy
Vimar A. Luz, MD, FPCP, DPSN
Gross Features:• paired retroperitoneal organ• Upper pole: T12; Lower pole: L3• Weight: adult man: 125 -170 g
adult woman: 115 - 155 g
• Length: 11 to 12 cm • Width: 5.0 to 7.5 cm• Thickness: 2.5 to 3.0 cm• Hilus: renal pelvis, the renal artery and
vein, the lymphatics, and a nerve.• Blood supply: single renal artery• Anterior branch: 3 segmental or lobar
arteries supply the upper, middle, and lower thirds of the anterior surface of the kidney
• Posterior branch: > ½ of the posterior surface; small apical segmental branch
Gross Features
Relation to other layers:
• The renal fascia relates to the other layers in
the following manner (moving from innermost
to outermost):
renal cortex
renal capsule
perinephric fat (or "perirenal fat")
renal fascia
paranephric fat (or "pararenal fat")
peritoneum (anteriorly)
transversalis fascia (posteriorly)
Cut surface of a bisected kidney:
• pale outer region
(the cortex) • darker inner region
(the medulla)
8 to 18 striated conical
masses (renal pyramids)
Base: corticomedullary boundary
Apex: renal pelvis to form a papilla : 10 - 25 small openings that represent the distal ends of the collecting ducts (of Bellini) area cribrosa
Renal cortex:
- 1 cm in thickness
- renal columns of Bertin
- "medullary rays of Ferrein“ - formed by the collecting ducts and the straight segments of the proximal and distal tubules.
• Renal pelvis: expanded portion of the upper urinary tract
• Major calyces: 2 or 3 outpouchings, extend outward from the upper dilated end of the renal pelvis
Ureters: lower portion of the renal pelvis at the ureteropelvic junction, descend a distance 28 - 34 cm to open into the fundus of the urinary bladder.
Minor calyces: extend toward the papillae of the pyramids and drain the urine formed by each pyramidal unit.
THE NEPHRON
• functional unit of the kidney 0.4 × 10 6 to 1.2 × 10 6
• Essenttal components:
renal or malpighian corpuscle (glomerulus and Bowman's capsule)
proximal tubule
the thin limbs
distal tubule
connecting segment or connecting tubule
Two main populations of nephrons:
(1) possessing a short loop of Henle (7x more)
(2) long loop of Henle
THE NEPHRON
• Length of the loop of Henle is generally related to the position of its parent glomerulus in the cortex.
• Superficial and midcortical locations : short loops of Henle• Juxtamedullary region: long loops of Henle
Division of the kidney (cortical & medullary )and the further subdivision of the medulla (inner and outer zones) : relating renal structure to the ability of an animal to form a maximally concentrated urine
Countercurrent hypothesis for urine : the maximal urine concentration that can be achieved is directly related to the length of the multiplier system.
Renal Corpuscle (Glomerulus)
• capillary network lined by a thin layer of endothelial cells
• central region of mesangial cells with surrounding mesangial matrix material
• the visceral epithelial cells (Podocytes) and the associated basement membrane
• average diameter: 200 µm• The diameters of glomeruli
from juxtamedullary nephrons: are 20% greater than superficial glomeruli
Renal Corpuscle (Glomerulus)
• Responsible for the production of an ultrafiltrate of plasma
• Filtration barrier 1.fenestrated endothelium 2.peripheral GBM3.slit pores between the foot processes of the visceral epithelial cells
• Mean area of filtration surface per glomerulus: 0.136 mm2 in the
human kidney
Mesangial cells
Visceral Epithelial cellParietal Epithelial cell
Endothelial cell
Endothelial cell
• glomerular capillaries are lined by a thin fenestrated endothelium
• human kidney range
fr 70 - 100 nm• Thin diaphragms: extend across
the fenestrae w/c when present,
are not believed to represent a
significant barrier to the passage
of macromolecules.• surface is negatively charged
because of the presence of a
polyanionic surface glycoprotein, podocalyxin (principal sialoprotein of glomerular epithelial cells)
Endothelial cell
• synthesize both nitric oxide (EDRF) and endothelin-1 (vasoconstrictor)
• Express vascular endothelial growth factor (VEGF) receptors• VEGF: regulator of microvascular permeability that is
produced by the glomerular VEC (Podocytes)
- In vitro studies demonstrated that VEGF increases endothelial cell permeability and induces the
formation of endothelial fenestrations.
- endothelial cell survival and repair in glomerular diseases and an important regulator of endothelial cell function and permeability.
• form the initial barrier to the passage of blood constituents from the capillary lumen to Bowman's space.
• contribute to the charge-selective properties of the glomerular capillary wall through their negative surface charge.
Visceral Epithelial Cells (podocytes)
• largest cells in the glomerulus• long cytoplasmic processes
(trabeculae) that extend from the
main cell body and divide into
individual foot processes (pedicels),
that come into direct contact with
the GBM.• Distance between adjacent foot
processes near the BM: 25 to 60 nm.• filtration slit membrane (slit
diaphragm) - 60 nm. fr the BM.
- role in establishing the permselec
tive properties of the filtration
barrier is still a matter of dispute.
Filtration slit / slit pore
Visceral Epithelial Cells (podocytes)
Nephrin protein - a key component of
filtration barrier• membrane components on the
surface of the visceral epithelial
cells (slit diaphragm)
CD2-associated protein (CD2AP) –
slit diaphragm; connect nephrin to cytoskeleton
Functions:
Endocytosis (lysosomes ) uptake of proteins and other components from the ultrafiltrate
Synthesis and maintenance of the GBM, type IV collagen, and glycosaminoglycan , PgE2 and thromboxanes.
Mesangial Cells
• Mesangium : cells + matrix• Irregular in shape, with a dense nucleus
and elongated cytoplasmic processes that
can extend around the capillary lumen and
insinuate themselves between the BM and
the overlying endothelium.• provides structural support for the
glomerular capillary loops• contractile properties • regulation of glomerular filtration• exhibit phagocytic properties (clearance or disposal of
macromolecules from the mesangium)• generation and metabolism of the extracellular mesangial
matrix and participate in various forms of glomerular injury
Glomerular Basement Membrane
• central dense layer (lamina densa)
two thinner, more electron-lucent
layers, the lamina rara externa and
the lamina rara interna• layered configuration results from
the fusion of endothelial and epithelial
BM during development.• mean width: 315 nm - 329 nm• biochemical composition:
glycoproteins (type IV collagen,
laminin, fibronectin, entactin/
nidogen, various heparan sulfate
proteoglycan (perlecan and agrin)
Glomerular Basement Membrane
• possesses fixed, negatively charged sites that influence the filtration of macromolecules
• anionic sites : glycosaminoglycans rich in heparan sulfate• Glomerular capillary wall: sieve or filter that allows the
passage of small molecules but almost completely restricts the passage of molecules the size of albumin or larger.
• size-selective and charge-selective properties • Fenestrated endothelium GBM epithelial slit
diaphragm• Fenestrated endothelium (negative surface charge) excludes
formed elements of the blood and probably plays a role in determining the access of proteins to the GBM - - - plays a role in establishing the ultrafiltration characteristics of the glomerular capillary wall.
• principal structure responsible for the charge-selective permeability properties of the glomerulus
Parietal Epithelial cells
• parietal epithelium: forms the outer wall
of Bowman's capsule
- continuous with the visceral epithelium
at the vascular pole.
- squamous in character, but at the
urinary pole there is an abrupt transition
to the taller cuboid cells of the proximal
tubule• thickness of the BM of Bowman's
capsule :1200 to 1500 nm.• In RPGN the parietal epithelial cells
proliferate to contribute to the formation
of crescents.
Peripolar Cells:
• component of the JG apparatus• located at the origin of the glomerular tuft in Bowman's space
and is interposed between the visceral and parietal epithelial cells
• In most animals studied so far, they have been localized predominantly in glomeruli in the outer cortex
• are ideally situated to release factors into Bowman's space that might affect subsequent tubule transport events.
Juxtaglomerular Apparatus
•
The Nephron: Juxtaglomerular Apparatus:
Juxtaglomerular Apparatus
• located at the vascular pole of the
glomerulus• Vascular component: composed of
the terminal portion of the afferent
arteriole, the initial portion of the
efferent arteriole, and the extraglo-
merular mesangial region. • Tubule component : macula densa,
(that portion of the thick ascending limb that is in contact with the vascular component)
• Represents a major structural component of the renin-angiotensin system.
• Role: regulate glomerular arteriolar resistance and GF and to control the synthesis and secretion of renin.
Juxtaglomerular Granular Cells
Within the vascular component:
1. Juxtaglomerular granular cells (epithelioid / myoepithelial cells)
2. Agranular extraglomerular mesangial cells (lacis cells or pseudomeissnerian cells of Goormaghtigh)
• Located primarily in the walls of the afferent and efferent arterioles, but they are also present in the extraglomerular mesangial region.
• are characterized by the presence of
numerous membrane-bound granules that
represent renin or its precursor. • Immunohistochemical studies: presence
of both renin and angiotensin II in the
JG granular cells, with activities being
highest in the afferent arteriole.
Extraglomerular Mesangium (Lacis / Cells of Goormaghtigh)
• Located between the afferent and efferent arterioles in close contact with the macula densa
• In contact with the arterioles and the macula densa, and gap junctions are commonly observed between the various cells of the vascular portion of the JG apparatus
• Serve as a functional link between the macula densa and the glomerular arterioles and mesangium.
EM
Macula Densa
• a specialized region of the thick
ascending limb adjacent to the
hilus of the glomerulus.• lacks the lateral cell processes and
interdigitations that are charac
teristic of the thick ascending limb.• sense changes in the luminal
concentrations of Na and Cl
via absorption of Na and Cl across the luminal membrane by the Na+ -K+ -2Cl- cotransporter.
Proximal Tubule
• begins abruptly at the urinary pole
of the glomerulus• Length:14 mm (human);
Outside diameter: 40 µm• Reabsorbs the bulk of filtered water and
solutes• Prominent brush border ( luminal cell
surface area) and extensive interdigita
tion by basolateral cell pro-
cesses that extends to the
leaky jxn providing a greatly in-
creased passage for the pas-
sive ion transport• Generally divided into 3
segments: S1, S2, S3
Proximal Tubule
It consists of:
Pars convoluta (initial convoluted portion)
- direct continuation of the parietal epithelium of Bowman's capsule
Pars recta (straight portion)
- located in the medullary ray; contains a well-developed endocytic-lysosomal apparatus that is involved in the reabsorption and degradation of macromolecules from the ultrafiltrate.
Loop of Henle:
Consists of:
1. Straight portion of the proximal tubule
2. Thin ascending limb
- impermeable to water
3. Thin descending limb
- highly permeable to water (aquaporin-1)
4. Thick ascending limb (diluting segment)
- water impermeable (carried away into the
cortex to the systemic circ.) but reabsorbs
considerable amounts of salt that is trap-
ped in the medulla(Na-K-2Cl cotransporter)
- Tam-Horsefall pretein
Before transition to the DCT. Thick AL contains
the macula densa.
Distal Covoluted Tubule
• Exhibits the most extensive basolateral
interdigitation of cells and greatest
density of mitochondria.• Na-Cl cotransporter – speific
Na transporter (Thiazide diuretics)
COLLECTING DUCT SYSTEMIncludes:
1. Connecting tubule
2. Cortical collecting ducts
3. Medullary CD
Outer MCD
Inner MCD
Connecting tubule (CNT) :- Joining of 2 nephrons- 2 types of cell:
1. CNT cell
2. Intercalated cell
Both share sensitivity to ADH; CNT cell lacks
sensitivity to mineralocorticoids
Collecting Ducts:
Lined by 2 types of cells:
1. Principal cells (CD)
Contain luminal shuttle system for
aquaporin -2 under the control of
vasopressin (permeability from zero
to permeable)• Luminal Amloride-sensitive Na channel – involved in the
responsiveness of the cortical collecting ducts to aldosterone.• Inner medulary collecting ducts – expresses urea transporter
UTB1 w/c in an ADH – dependent fashion accounts for the recycling of urea (urine concentrating mechanism)
Collecting Ducts:
2. Intercalated cells (IC)
2 types:
a. Type A cells – express H-ATPase at
their luminal memb.; secretes proton
b. Type B – basolateral membrane;
secrete HCO3 ions and reabsorb
protons.• Final regulators of fluid and electrolye balance• Impt roles in handling NA,Cl, K and acid-base.• Urine concentrating capability
INTERSTITIUM
• Comparatively sparse:
5-7%: cortex ( w/ age); 3-4%: outer stripe; 10%: inner stripe
30%: inner medulla• Fibroblast: central cells; forms the scaffold frame
renal cortex: ecto 5 nucleotidas enzyme (5’-NT) – synthesizes epoetin
renal medulla: Lipid-laden IC; produce large amount of glycosaminoglycans and Vasoactive lipids (Pg E2)
• Dendritic cells- MHC class II antigen• Extracellular matrix, fibrils and interstitial fluid
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Renal Anatomy
Rosella N. Blancas, M.D.
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