Kidney Anatomy and
Physiology
Presented by Ifeoma Ezeonyebuchi
1
Kidney Functions
• Regulating total water volume and total solute concentration
in water
• Regulating ECF ion concentrations
• Ensuring long-term acid-base balance
• Removal of metabolic wastes, toxins, drugs
2
Kidney Functions
• Endocrine functions
• Renin - regulation of blood pressure
• Erythropoietin - regulation of RBC production
• Activation of vitamin D
• Gluconeogenesis during prolonged fasting
3
Urinary System Organs
•
•
•
•
Kidneys - major excretory organs
Ureters - transport urine from kidneys to urinary bladder
Urinary bladder - temporary storage reservoir for urine
Urethra transports urine out of body
4
Figure 25.1 The urinary system.
Hepatic veins (cut)
Esophagus (cut)
Inferior vena cava
Adrenal gland
Renal artery
Renal hilum
Aorta
Renal vein
Kidney
Iliac crest
Ureter
Rectum (cut)
Uterus (part of female
reproductive system)
Urinary
bladder
5
Urethra
Kidney Anatomy
•
•
•
•
Retroperitoneal, in the superior lumbar region; ~ T12 to L5
Right kidney crowded by liver  lower than left
Adrenal (suprarenal) gland atop each kidney
Convex lateral surface, concave medial surface; vertical renal
hilum leads to renal sinus
• Ureters, renal blood vessels, lymphatics, and nerves enter and
exit at hilum
6
Figure 25.2b Positionof the kidneysagainst the posteriorbody wall.
12th rib
7
Kidney Anatomy
• Layers of surrounding supportive tissue
• Renal fascia
• Anchoring outer layer of dense fibrous connective tissue
• Perirenal fat capsule
• Fatty cushion
• Fibrous capsule
• Prevents spread of infection to kidney
8
Internal Anatomy
• Renal cortex
• Granular-appearing superficial region
• Renal medulla
• Composed of cone-shaped medullary (renal) pyramids
• Pyramids separated by renal columns
• Inward extensions of cortical tissue
9
Internal Anatomy
• Papilla
• Tip of pyramid; releases urine into minor calyx
• Lobe
• Medullary pyramid and its surrounding cortical tissue; ~ 8/kidney
• Renal pelvis
• Funnel-shaped tube continuous with ureter
10
Internal Anatomy
• Minor calyces
• Drain pyramids at papillae
• Major calyces
• Collect urine from minor calyces
• Empty urine into renal pelvis
• Urine flow
• Renal pyramid  minor calyx  major calyx  renal pelvis 
ureter
11
Homeostatic Imbalance
• Pyelitis
• Infection of renal pelvis and calyces
• Pyelonephritis
• Infection/inflammation of entire kidney
• Normally - successfully treated with antibiotics
12
Figure 25.2a Position of the kidneys against the posteriorbody wall.
Anterior
Inferior
vena cava
Aorta
Peritoneum
Peritoneal cavity
(organs removed)
Supportive
tissue layers
• Renal fascia
anterior
posterior
Renal
vein
Renal
artery
• Perirenal
fat capsule
• Fibrous
capsule
Body of
vertebra L2
Body wall
13
Posterior
Figure 25.3 Internalanatomy of the kidney.
Renal
hilum
Renal cortex
Renal medulla
Major calyx
Papilla of
pyramid
Renal pelvis
Minor calyx
Ureter
Renal pyramid in
renal medulla
Renal column
Fibrous capsule
Photograph of right kidney, frontal section
14
Diagrammatic view
Blood and Nerve Supply
• Kidneys cleanse blood; adjust its composition  rich blood
supply
• Renal arteries deliver ~ ¼ (1200 ml) of cardiac output to
kidneys each minute
• Arterial flow into and venous flow out of kidneys follow similar
paths
• Nerve supply via sympathetic fibers from renal plexus
15
Figure 25.4a Blood vesselsof the kidney.
Cortical radiate
vein
Cortical radiate
artery
Arcuate vein
Arcuate artery
Interlobar vein
Interlobar artery
Segmental arteries
Renal vein
Renal artery
Renal pelvis
Ureter
Renal medulla
Renal cortex
Frontal section illustrating major blood vessels
16
Aorta
Inferior vena cava
Renal artery
Renal vein
Segmental artery
Interlobar vein
Interlobar artery
Arcuate vein
Arcuate artery
Cortical radiate artery
Afferent arteriole
Cortical radiate vein
Peritubular
capillaries
or vasa recta
Efferent arteriole
Glomerulus (capillaries)
17
Nephron-associated blood vessels
(see Figure 25.7)
(b) Path of blood flow through renal blood vessels
Nephrons
• Structural and functional units that form urine
• > 1 million per kidney
• Two main parts
• Renal corpuscle filtration unit (glomerulus and Bowman’s
capsule)
• Renal tubule regions of the nephron responsible for the
reabsorption of substances back into the blood supply
18
Renal Corpuscle
• Two parts of renal corpuscle
• Glomerulus
• Tuft of capillaries; fenestrated endothelium  highly porous 
allows filtrate formation
• Glomerular capsule (Bowman's capsule)
• Cup-shaped, hollow structure surrounding glomerulus
19
Figure 25.5 Locationand structureof nephrons.
Renal cortex
Renal medulla
Glomerular capsule: parietal layer
Renal pelvis
Ureter
Kidney
Renal corpuscle
• Glomerular capsule
• Glomerulus
Distal
convoluted
tubule
Basement
membrane
Podocyte
Fenestrated endothelium
of the glomerulus
Glomerular capsule: visceral layer
Apical
microvilli
Mitochondria
Highly infolded basolateral
membrane
Proximal convoluted tubule cells
Proximal
convoluted
tubule
Cortex
Apical side
Medulla
Thin segment
Nephron loop
• Descending limb
• Ascending limb
Thick
segment
Basolateral side
Distal convoluted tubule cells
Nephron loop (thin-segment) cells
Collecting
duct
Principal
cell
Intercalated cell
Collecting duct cells
20
Renal Tubule
• Glomerular capsule
• Parietal layer - simple squamous epithelium
• Visceral layer - branching epithelial podocytes
• Extensions terminate in foot processes that cling to basement
membrane
• Filtration slits between foot processes allow filtrate to pass into
capsular space
21
Figure 25.5 Locationand structureof nephrons.(2 of 7)
Glomerular capsule: parietal layer
22
Figure 25.5 Locationand structureof nephrons.(3 of 7)
Basement
membrane
Podocyte
Fenestrated endothelium
of the glomerulus
Glomerular capsule: visceral layer
23
Renal Tubule
• Three parts
• Proximal convoluted tubule
• Proximal  closest to renal corpuscle
• Nephron loop
• Distal convoluted tubule
• Distal  farthest from renal corpuscle
24
Renal Tubule
• Proximal convoluted tubule (PCT)
• Cuboidal cells with dense microvilli (brush border  surface
area); large mitochondria
• Functions in reabsorption and secretion
• Confined to cortex
25
Figure 25.5 Locationand structureof nephrons.(4 of 7)
Apical microvilli
Mitochondria
Highly infolded
basolateral membrane
Proximal convoluted tubule cells
26
Renal Tubule
• Nephron loop
• Descending and ascending limbs
• Proximal descending limb continuous with proximal tubule
• Distal descending limb = descending thin limb; simple squamous
epithelium
• Thick ascending limb
• Cuboidal to columnar cells; thin in some nephrons
27
Figure 25.5 Locationand structureof nephrons.(6 of 7)
Nephron loop (thin-segment) cells
28
Renal Tubule
• Distal convoluted tubule (DCT)
• Cuboidal cells with very few microvilli
• Function more in secretion than reabsorption
• Confined to cortex
29
Figure 25.5 Locationand structureof nephrons.(5 of 7)
Apical side
Basolateral side
Distal convoluted tubule cells
30
Collecting Ducts
• Two cell types
• Principal cells
• Sparse, short microvilli
• Maintain water and Na+ balance
• Intercalated cells
• Cuboidal cells; abundant microvilli; two types
• A and B; both help maintain acid-base balance of blood
31
Figure 25.5 Locationand structureof nephrons.(7 of 7)
Principal cell
Intercalated cell
Collecting duct cells
32
Collecting Duct
• Receive filtrate from many nephrons
• Run through medullary pyramids  striped appearance
• Fuse together to deliver urine through papillae into minor
calyces
33
Classes of Nephrons
• Cortical nephrons—85% of nephrons; almost entirely in cortex
• Juxtamedullary nephrons
• Long nephron loops deeply invade medulla
• Ascending limbs have thick and thin segments
• Important in production of concentrated urine
34
Cortical nephron
• Short nephron loop
• Glomerulus further from the cortex-medulla junction
• Efferent arteriole supplies peritubular capillaries
Glomerulus
Renal
corpuscle (capillaries)
Glomerular
capsule
Efferent
arteriole
Proximal
convoluted
tubule
Juxtamedullary nephron
• Long nephron loop
• Glomerulus closer to the cortex-medulla junction
• Efferent arteriole supplies vasa recta
Cortical radiate vein
Cortical radiate artery
Afferent arteriole
Collecting duct
Distal convoluted tubule
Afferent
Efferent
arteriole
arteriole
Peritubular
capillaries
Ascending
limb of
nephron loop
Kidney
Cortex-medulla
junction
Arcuate vein
Arcuate artery
Vasa recta
Nephron loop
Descending
limb of
nephron loop
35
Nephron Capillary Beds
• Renal tubule associated with two capillary beds
• Glomerulus
• Peritubular capillaries
• Juxtamedullary nephron associated with
• Vasa recta
36
Nephron Capillary Beds
• Glomerulus - specialized for filtration
• Different from other capillary beds – fed and drained by
arteriole
• Afferent arteriole  glomerulus  efferent arteriole
• Blood pressure in glomerulus high because
• Afferent arterioles larger in diameter than efferent arterioles
• Arterioles are high-resistance vessels
37
Nephron Capillary Beds
• Peritubular capillaries
• Low-pressure, porous capillaries adapted for absorption of water
and solutes
• Arise from efferent arterioles
• Cling to adjacent renal tubules in cortex
• Empty into venules
38
Nephron Capillary Beds
• Vasa recta
• Long, thin-walled vessels parallel to long nephron loops of
juxtamedullary nephrons
• Arise from efferent arterioles serving juxtamedullary nephrons
• Instead of peritubular capillaries
• Function in formation of concentrated urine
39
Juxtaglomerular Complex (JGC)
• One per nephron
• Involves modified portions of
• Distal portion of ascending limb of nephron loop
• Afferent (sometimes efferent) arteriole
• Important in regulation of rate of filtrate formation and blood
pressure
40
Juxtaglomerular Complex (JGC)
• Three cell populations
• Macula densa, granular cells, extraglomerular mesangial cells
• Macula densa
• Tall, closely packed cells of ascending limb
• Chemoreceptors; sense NaCl content of filtrate
41
Juxtaglomerular Complex (JGC)
• Granular cells (juxtaglomerular, or JG cells)
• Enlarged, smooth muscle cells of arteriole
• Secretory granules contain enzyme renin
• Mechanoreceptors; sense blood pressure in afferent arteriole
42
Juxtaglomerular Complex (JGC)
• Extraglomerular mesangial cells
• Between arteriole and tubule cells
• Interconnected with gap junctions
• May pass signals between macula densa and granular cells
43
Figure 25.8 Juxtaglomerularcomplex(JGC) of a nephron.
Glomerular
capsule
Efferent
arteriole
Afferent
arteriole
Glomerulus
Parietal layer
of glomerular
capsule
Capsular
space
Foot
processes
of podocytes
Podocyte cell body
(visceral layer)
Red blood cell
Proximal
tubule cell
Efferent
arteriole
Juxtaglomerular
complex
• Macula densa
cells
of the ascending
limb of nephron loop
• Extraglomerular
mesangial cells
• Granular
cells
Afferent
arteriole
Lumens of
glomerular
capillaries
Endothelial cell
of glomerular
capillary
Glomerular mesangial
cells
Juxtaglomerular complex
Renal corpuscle
44
Kidney Physiology: Mechanisms
of Urine Formation
• 180 L fluid processed daily; only 1.5 L  urine
• Three processes in urine formation and adjustment of blood
composition
• Glomerular filtration
• Tubular reabsorption
• Tubular secretion
45
Kidney Physiology: Mechanisms
of Urine Formation
• Glomerular filtration – produces cell- and protein-free filtrate
• Tubular reabsorption
• Selectively returns 99% of substances from filtrate to blood in
renal tubules and collecting ducts
• Tubular secretion
• Selectively moves substances from blood to filtrate in renal
tubules and collecting ducts
46
Kidney Physiology: Mechanisms
of Urine Formation
• Kidneys filter body's entire plasma volume 60 times each day;
consume 20-25% oxygen used by body at rest; produce urine
from filtrate
• Filtrate (produced by glomerular filtration)
• Blood plasma minus proteins
• Urine
• <1% of original filtrate
• Contains metabolic wastes and unneeded substances
47
Figure 25.9 A schematic,uncoiled nephron showingthe three major renal processesthat adjust plasma composition.
Afferent
arteriole
Glomerular
capillaries
Efferent arteriole
Cortical
radiate
artery
1
Glomerular capsule
Renal tubule and
collecting duct
containing filtrate
2
Peritubular
capillary
3
To cortical radiate vein
Three major
renal processes: Urine
Glomerular filtration
1
Tubular reabsorption
2
Tubular secretion
3
48
Glomerular Filtration
• Passive process
• No metabolic energy required
• Hydrostatic pressure forces fluids and solutes through
filtration membrane
• No reabsorption into capillaries of glomerulus
49
The Filtration Membrane
• Porous membrane between blood and interior of glomerular
capsule
• Water, solutes smaller than plasma proteins pass; normally no
cells pass
• Three layers
• Fenestrated endothelium of glomerular capillaries
• Basement membrane (fused basal laminae of two other layers)
• Foot processes of podocytes with filtration slits; slit diaphragms
repel macromolecules
50
Figure 25.10a The filtration membrane.
Efferent
arteriole
Glomerular
capsular space
Cytoplasmic extensions
of podocytes
Filtration slits
Podocyte
cell body
Afferent
arteriole
Glomerular
capillary covered by
podocytes that form
the visceral layer of
glomerular capsule
Proximal
convoluted
tubule
Parietal layer
Fenestrations
of glomerular
(pores)
capsule
Glomerular capillaries and the
visceral layer of the glomerular
capsule
Glomerular
capillary endothelium
(podocyte covering
and basement
membrane removed)
Foot
processes
of podocyte
51
Figure 25.10b The filtration membrane.
Filtration slits
Podocyte
cell body
Foot
processes
52
Filtration slits between the podocyte foot processes
Figure 25.10c The filtrationmembrane.
Capillary
Filtration membrane
• Capillary endothelium
• Basement membrane
• Foot processes of podocyte
of glomerular capsule
Filtration
slit
Plasma
Fenestration
(pore)
Filtrate
in capsular
space
Slit
diaphragm
Foot
processes
of podocyte
Three layers of the filtration membrane
53
The Filtration Membrane
• Macromolecules "stuck" in filtration
membrane engulfed by glomerular
mesangial cells
• Allows molecules smaller than 3 nm to
pass
• Water, glucose, amino acids, nitrogenous wastes
• Plasma proteins remain in blood 
maintains colloid osmotic pressure 
prevents loss of all water to capsular space
• Proteins in filtrate indicate membrane problem
54
OBJECTIVES:
Kidney Physiology: Mechanisms of Urine Formation:
4. Describe the forces (pressures) that promote or counteract glomerular filtration.
5. Compare the intrinsic and extrinsic controls of the glomerular filtration rate.
6. Describe the mechanisms underlying water and solute reabsorption from the renal tubules into
the peritubular capillaries.
7. Describe how sodium and water reabsorption are regulated in the distal tubule and
collecting duct.
8. Describe the importance of tubular secretion and list several substances that are secreted.
9. Describe the mechanisms responsible for the medullary osmotic gradient.
10. Explain formation of dilute versus concentrated urine.
55
Pressures That Affect Filtration
• Outward pressures promote filtrate formation
• Hydrostatic pressure in glomerular capillaries = Glomerular
blood pressure
• Chief force pushing water, solutes out of blood
• Quite high – 55 mm Hg (most capillary beds ~ 26 mm Hg)
• Because efferent arteriole is high resistance vessel with diameter smaller
than afferent arteriole
56
Pressures That Affect Filtration
• Inward forces inhibiting filtrate formation
• Hydrostatic pressure in capsular space (HPcs)
• Pressure of filtrate in capsule – 15 mm Hg
• Colloid osmotic pressure in capillaries (OPgc)
• "Pull" of proteins in blood – 30 mm Hg
• Sum of forces  Net filtration pressure (NFP)
• 55 mm Hg forcing out; 45 mm Hg opposing = net outward force of
10 mm Hg
57
Net Filtration Pressure (NFP)
• Pressure responsible for filtrate formation (10 mm Hg)
• Main controllable factor determining glomerular filtration
rate (GFR)
58
Figure 25.11 Forces determiningnet filtration pressure(NFP).
Efferent
arteriole
Glomerular
capsule
HPgc = 55 mm Hg
OPgc = 30 mm Hg
Afferent
arteriole
HPcs = 15 mm Hg
NFP = Net filtration pressure
= outward pressures – inward pressures
= (HPgc) – (HPcs + OPgc)
= (55) – (15 + 30)
= 10 mm Hg
59
Glomerular Filtration Rate
(GFR)
• Volume of filtrate formed per minute by both kidneys (normal
= 120–125 ml/min)
• GFR directly proportional to
• NFP – primary pressure is hydrostatic pressure in glomerulus
• Total surface area available for filtration – glomerular mesangial
cells control by contracting
• Filtration membrane permeability – much more permeable than
other capillaries
60
Regulation of Glomerular
Filtration
• Constant GFR allows kidneys to make filtrate and maintain
extracellular homeostasis
• Goal of intrinsic controls - maintain GFR in kidney
• GFR affects systemic blood pressure
•  GFR  urine output   blood pressure, and vice versa
• Goal of extrinsic controls - maintain systemic blood pressure
61
Regulation of Glomerular
Filtration
• Intrinsic controls (renal autoregulation)
• Act locally within kidney to maintain GFR
• Extrinsic controls
• Nervous and endocrine mechanisms that maintain blood
pressure; can negatively affect kidney function
• Take precedence over intrinsic controls if systemic BP < 80 or >
180 mm Hg
62
Regulation of Glomerular
Filtration
• Controlled via glomerular hydrostatic pressure
• If rises  NFP rises  GFR rises
• If falls only 18% GFR = 0
63
Intrinsic Controls
• Maintains nearly constant GFR when MAP in range of 80–
180 mm Hg
• Autoregulation ceases if out of that range
• Two types of renal autoregulation
• Myogenic mechanism
• Tubuloglomerular feedback mechanism
64
Intrinsic Controls: Myogenic
Mechanism
• Smooth muscle contracts when stretched
•  BP  muscle stretch  constriction of afferent arterioles 
restricts blood flow into glomerulus
• Protects glomeruli from damaging high BP
•  BP  dilation of afferent arterioles
• Both help maintain normal GFR despite normal fluctuations in
blood pressure
65
Intrinsic Controls:
Tubuloglomerular Feedback
Mechanism
• Flow-dependent mechanism directed by macula densa cells;
respond to filtrate NaCl concentration
• If GFR  filtrate flow rate   reabsorption time  high
filtrate NaCl levels  constriction of afferent arteriole  
NFP & GFR  more time for NaCl reabsorption
• Opposite for  GFR
66
Extrinsic Controls:
Sympathetic Nervous System
• Under normal conditions at rest
• Renal blood vessels dilated
• Renal autoregulation mechanisms prevail
67
Extrinsic Controls:
Sympathetic Nervous System
• If extracellular fluid volume extremely low (blood pressure
low)
• Norepinephrine released by sympathetic nervous system;
epinephrine released by adrenal medulla 
• Systemic vasoconstriction  increased blood pressure
• Constriction of afferent arterioles   GFR  increased blood
volume and pressure
68
Extrinsic Controls: ReninAngiotensin- Aldosterone Mechanism
• Main mechanism for increasing blood pressure – see Chapters
16 and 19
• Three pathways to renin release by granular cells
• Direct stimulation of granular cells by sympathetic nervous
system
• Stimulation by activated macula densa cells when filtrate NaCl
concentration low
• Reduced stretch of granular cells
69
Extrinsic Controls: Other
Factors Affecting GFR
• Kidneys release chemicals; some act as paracrines that affect
renal arterioles
• Adenosine
• Prostaglandin E2
• Intrinsic angiotensin II – reinforces effects of hormonal
angiotensin II
70
Tubular Reabsorption
• Most of tubular contents reabsorbed to blood
• Selective transepithelial process
• ~ All organic nutrients reabsorbed
• Water and ion reabsorption hormonally regulated and adjusted
• Includes active and passive tubular reabsorption
• Two routes
• Transcellular or paracellular
71
Tubular Reabsorption
• Transcellular route
•
•
•
•
Apical membrane of tubule cells 
Cytosol of tubule cells 
Basolateral membranes of tubule cells 
Endothelium of peritubular capillaries
72
Tubular Reabsorption
• Paracellular route
• Between tubule cells
• Limited by tight junctions, but leaky in proximal nephron
• Water, Ca2+, Mg2+, K+, and some Na+ in the PCT
73
Figure 25.13 Transcellularand paracellularroutes of tubular reabsorption.
Slide 1
The paracellular route
The transcellular route 3 Transport across the
involves:
basolateral membrane. (Often
involves:
•
Movement through leaky
involves the lateral intercellular
1 Transport across the spaces because membrane
tight junctions, particularly in
apical membrane.
the PCT.
transporters transport ions into
• Movement through the inter2 Diffusion through the these spaces.)
stitial fluid and into the
4 Movement through the intercytosol.
capillary.
stitial fluid and into the capillary.
Filtrate
Tubule cell
Interstitial fluid
in tubule
PeriLateral
Tight junction
lumen
tubular
intercellular capillary
space
3
H2O and
solutes
Apical
membrane
H2O and
solutes
1
2
4
3
4
Transcellular Capillary
endothelial
route
cell
Paracellular route
74
Basolateral
membranes
Tubular Reabsorption of
Sodium
• Na+ - most abundant cation in filtrate
• Transport across basolateral membrane
• Primary active transport out of tubule cell by
Na+-K+ ATPase pump  peritubular capillaries
• Transport across apical membrane
• Na+ passes through apical membrane by secondary active transport
or facilitated diffusion mechanisms
75
Reabsorption of Nutrients,
Water, and Ions
• Na+ reabsorption by primary active transport provides energy
and means for reabsorbing most other substances
• Creates electrical gradient  passive reabsorption of anions
• Organic nutrients reabsorbed by secondary active transport;
cotransported with Na+
• Glucose, amino acids, some ions, vitamins
76
Passive Tubular Reabsorption
of Water
• Movement of Na+ and other solutes creates osmotic gradient
for water
• Water reabsorbed by osmosis, aided by water-filled pores
called aquaporins
• Aquaporins always present in PCT  obligatory water
reabsorption
• Aquaporins inserted in collecting ducts only if ADH present 
facultative water reabsorption
77
Passive Tubular Reabsorption
of Solutes
• Solute concentration in filtrate increases as water reabsorbed
 concentration gradients for solutes 
• Fat-soluble substances, some ions and urea, follow water into
peritubular capillaries down concentration gradients
•  Lipid-soluble drugs, environmental pollutants difficult to
excrete
78
Figure 25.14 Reabsorptionby PCT cells.
Slide 1
1 At the basolateral membrane, Na+ is
pumped into the interstitial space by the
Na+-K+ ATPase. Active Na+ transport
creates concentration gradients that drive:
Nucleus
Filtrate
in tubule
lumen
Tubule cell
Interstitial
fluid
Peritubular
capillary
2
Glucose
Amino
acids
Some
ions
Vitamins
1
3
4
Lipid5
soluble
substances
6
Various
Ions
and urea
2 “Downhill” Na+ entry at the
apical membrane.
3 Reabsorption of organic
nutrients and certain ions by
cotransport at the apical
membrane.
4 Reabsorption of water by
osmosis through
aquaporins. Water
reabsorption increases the
concentration of the
solutes that are left behind.
These solutes can then be
reabsorbed as they move
down their gradients:
5 Lipid-soluble substances
diffuse by the transcellular
route.
Tight junction
Primary active transport
Secondary active transport
Passive transport (diffusion)
Paracellular
route
Transport protein
Ion channel
Aquaporin
6 Various ions (e.g., Cl−,
Ca2+, K+) and urea diffuse
by the paracellular route.
79
Transport Maximum
• Transcellular transport systems specific and limited
• Transport maximum (Tm) for ~ every reabsorbed substance;
reflects number of carriers in renal tubules available
• When carriers saturated, excess excreted in urine
• E.g., hyperglycemia  high blood glucose levels exceed Tm 
glucose in urine
80
Reabsorptive Capabilities of
Renal Tubules and Collecting
Ducts
• PCT
• Site of most reabsorption
•
•
•
•
All nutrients, e.g., glucose and amino acids
65% of Na+ and water
Many ions
~ All uric acid; ½ urea (later secreted back into filtrate)
81
Reabsorptive Capabilities of
Renal Tubules and Collecting
Ducts
• Nephron loop
• Descending limb - H2O can leave; solutes cannot
• Ascending limb – H2O cannot leave; solutes can
• Thin segment – passive Na+ movement
• Thick segment – Na+-K+-2Cl- symporter and Na+-H+ antiporter; some
passes by paracellular route
82
Reabsorptive Capabilities of
Renal Tubules and Collecting
Ducts
• DCT and collecting duct
• Reabsorption hormonally regulated
•
•
•
•
Antidiuretic hormone (ADH) – Water
Aldosterone – Na+ (therefore water)
Atrial natriuretic peptide (ANP) – Na+
PTH – Ca2+
83
Reabsorptive Capabilities of
Renal Tubules and Collecting
Ducts
• Antidiuretic hormone (ADH)
• Released by posterior pituitary gland
• Causes principal cells of collecting ducts to insert aquaporins in
apical membranes  water reabsorption
• As ADH levels increase  increased water reabsorption
84
Reabsorptive Capabilities of Renal
Tubules and Collecting Ducts
• Aldosterone
• Targets collecting ducts (principal cells) and distal DCT
• Promotes synthesis of luminal Na+ and K+ channels, and
basolateral Na+-K+ ATPases for Na+ reabsorption; water follows
•  little Na+ leaves body; aldosterone absence  loss of 2%
filtered Na+ daily - incompatible with life
• Functions – increase blood pressure; decrease K+ levels
85
Reabsorptive Capabilities of Renal
Tubules and Collecting Ducts
• Atrial natriuretic peptide
• Reduces blood Na+  decreased blood volume and blood
pressure
• Released by cardiac atrial cells if blood volume or pressure
elevated
• Parathyroid hormone acts on DCT to increase Ca2+
reabsorption
86
Tubular Secretion
• Reabsorption in reverse; almost all in PCT
• Selected substances
• K+, H+, NH4+, creatinine, organic acids and bases move from
peritubular capillaries through tubule cells into filtrate
• Substances synthesized in tubule cells also secreted – e.g., HCO3-
87
Tubular Secretion
• Disposes of substances (e.g., drugs) bound to plasma proteins
• Eliminates undesirable substances passively reabsorbed (e.g.,
urea and uric acid)
• Rids body of excess K+ (aldosterone effect)
• Controls blood pH by altering amounts of H+ or HCO3– in urine
88
Figure 25.15 Summary of tubular reabsorptionand secretion.
Cortex
65% of filtrate volume
reabsorbed
• H2O
• Na+, HCO3−, and
many other ions
• Glucose, amino acids,
and other nutrients
• H+ and NH4+
• Some drugs
Outer
medulla
Regulated reabsorption
• Na+ (by aldosterone;
Cl− follows)
• Ca2+ (by parathyroid
hormone)
Regulated
secretion
• K+ (by
aldosterone)
Regulated
reabsorption
• H2O (by ADH)
• Na+ (by
aldosterone; Cl−
follows)
• Urea (increased
by ADH)
• Urea
Inner
medulla
Regulated
secretion
• K+ (by
aldosterone)
• Reabsorption or secretion
to maintain blood pH
described in Chapter 26;
involves H+, HCO3−,
and NH4+
Reabsorption
Secretion
89
Regulation of Urine
Concentration and Volume
• Osmolality
• Number of solute particles in 1 kg of H2O
• Reflects ability to cause osmosis
90
Regulation of Urine
Concentration and Volume
• Osmolality of body fluids
• Expressed in milliosmols (mOsm)
• Kidneys maintain osmolality of plasma at ~300 mOsm by
regulating urine concentration and volume
• Kidneys regulate with countercurrent mechanism
91
Countercurrent Mechanism
• Occurs when fluid flows in opposite directions in two adjacent
segments of same tube with hair pin turn
• Countercurrent multiplier – interaction of filtrate flow in
ascending/descending limbs of nephron loops of juxtamedullary
nephrons
• Countercurrent exchanger - Blood flow in ascending/descending
limbs of vasa recta
92
Countercurrent Mechanism
• Role of countercurrent mechanisms
• Establish and maintain osmotic gradient (300 mOsm to
1200 mOsm) from renal cortex through medulla
• Allow kidneys to vary urine concentration
93
Figure 25.16a Juxtamedullarynephronscreate an osmoticgradient within the renal medulla that allows the kidney to produce urine of varying concentration.(1 of 4)
The three key players and their
orientation in the osmotic gradient:
(c) The collecting ducts of
all nephrons use the gradient
to adjust urine osmolality.
300
300
(a) The long nephron loops of
juxtamedullary nephrons create
the gradient. They act as
countercurrent multipliers.
400
600
900
(b) The vasa recta preserve the
gradient. They act as
countercurrent exchangers.
1200
The osmolality of the medullary
interstitial fluid progressively
increases from the 300 mOsm of
normal body fluid to 1200 mOsm
at the deepest part of the medulla.
94
Countercurrent Multiplier:
Loop of Henle
• Descending limb
• Freely permeable to H2O
• H2O passes out of filtrate into hyperosmotic medullary interstitial
fluid
• Filtrate osmolality increases to ~1200 mOsm
95
Countercurrent Multiplier:
Loop of Henle
• Ascending limb
• Impermeable to H2O
• Selectively permeable to solutes
• Na+ and Cl– actively reabsorbed in thick segment; some passively
reabsorbed in thin segment
• Filtrate osmolality decreases to 100 mOsm
96
The Countercurrent Multiplier
• Constant 200 mOsm difference between two limbs of nephron
loop and between ascending limb and interstitial fluid
• Difference "multiplied" along length of loop to ~ 900 mOsm
97
The Countercurrent Exchanger
• Vasa recta
• Preserve medullary gradient
• Prevent rapid removal of salt from interstitial space
• Remove reabsorbed water
• Water entering ascending vasa recta either from descending
vasa recta or reabsorbed from nephron loop and collecting
duct 
• Volume of blood at end of vasa recta greater than at beginning
98
Figure 25.16a Juxtamedullarynephronscreate an osmoticgradient within the renal medulla that allows the kidney to produce urine of varying concentration.(2 of 4)
Long nephron loops of juxtamedullary nephrons create the gradient.
The countercurrent multiplier depends on three properties
of the nephron loop to establish the osmotic gradient.
Fluid flows in the
opposite direction
(countercurrent)
through two
adjacent parallel
sections of a
nephron loop.
The descending
limb is permeable
to water, but not
to salt.
The ascending limb
is impermeable to
water, and pumps
out salt.
99
Figure 25.16a Juxtamedullarynephronscreate an osmoticgradient within the renal medulla that allows the kidney to produce urine of varying concentration.(3 of 4)
Long nephron loops of juxtamedullary nephrons create the gradient.
These properties establish a positive feedback cycle that
uses the flow of fluid to multiply the power of the salt pumps.
Interstitial fluid
osmolality
Start
here
Water leaves the
descending limb
Osmolality of filtrate
in descending limb
Salt is pumped out
of the ascending limb
Osmolality of filtrate
entering the ascending
limb
100
Figure 25.16a Juxtamedullarynephronscreate an osmoticgradient within the renal medulla that allows the kidney to produce urine of varying concentration.(4 of 4)
(continued) As water and solutes are reabsorbed, the loop first concentrates the filtrate, then dilutes it.
Active transport
Passive transport
Water impermeable
300
300
Osmolality of interstitial fluid (mOsm)
300
100
Cortex
1 Filtrate entering the
nephron loop is isosmotic to
both blood plasma and
cortical interstitial fluid.
400
600
300
100
5 Filtrate is at its most dilute as it
leaves the nephron loop. At
100 mOsm, it is hypo-osmotic
to the interstitial fluid.
400
200
4 Na+ and Cl- are pumped out
of the filtrate. This increases the
interstitial fluid osmolality.
Outer
medulla
600
400
900
700
2 Water moves out of the
filtrate in the descending limb
down its osmotic gradient.
This concentrates the filtrate.
900
1200
Inner
medulla
3 Filtrate reaches its highest
concentration at the bend of the
loop.
Nephron loop
1200
101
Figure 25.16b Juxtamedullarynephronscreate an osmoticgradient within the renal medulla that allows the kidney to produce urine of varying concentration.
Vasa recta preserve the gradient.
The entire length of the vasa recta is highly permeable to water
and solutes. Due to countercurrent exchanges between each
section of the vasa recta and its surrounding interstitial fluid, the
blood within the vasa recta remains nearly isosmotic to the
surrounding fluid. As a result, the vasa recta do not undo the
osmotic gradient as they remove reabsorbed water and solutes.
Blood from
efferent
arteriole
To vein
325
300
300
400
The countercurrent
flow of fluid moves
through two adjacent
parallel sections of
the vasa recta.
400
600
600
900
102
900
Vasa recta
1200
Figure 25.16c Juxtamedullarynephronscreate an osmoticgradient within the renal medulla that allows the kidney to produce urine of varying concentration.
Collecting ducts use the gradient.
Under the control of antidiuretic hormone, the collecting
ducts determine the final concentration and volume of
urine. This process is fully described in Figure 25.17.
Collecting duct
400
600
900
Osmolality of interstitial fluid (mOsm)
300
103
Urine
1200
Formation of Dilute or
Concentrated Urine
• Osmotic gradient used to raise urine concentration > 300
mOsm to conserve water
• Overhydration  large volume dilute urine
• ADH production ; urine ~ 100 mOsm
• If aldosterone present, additional ions removed  ~ 50 mOsm
• Dehydration  small volume concentrated urine
• ADH released; urine ~ 1200 mOsm
• Severe dehydration – 99% water reabsorbed
104
Figure 25.17 Mechanismfor forming dilute or concentratedurine.
If we were so overhydrated we had no ADH...
If we were so dehydrated we had maximal ADH...
Osmolality of extracellular fluids
Osmolality of extracellular fluids
ADH release from posterior pituitary
ADH release from posterior pituitary
Number of aquaporins (H2O channels) in collecting duct
Number of aquaporins (H2O channels) in collecting duct
H2O reabsorption from collecting duct
H2O reabsorption from collecting duct
Large volume of dilute urine
Small volume of concentrated urine
Collecting
duct
Cortex
100
600
300
400
600
100
Outer
medulla
900
700
900
1200
300
300
100
300
300
400
600
400
600
600
900
900
Outer
medulla
Urea
700
900
Urea
100
Inner
medulla
1200
Large volume
of dilute urine
Active transport
Passive transport
150
Cortex
Urea
Inner
medulla
300
100
DCT
100
Osmolality of interstitial fluid (mOsm)
DCT
300
Descending limb
of nephron loop
300
100
Osmolality of interstitial fluid (mOsm)
Descending limb
of nephron loop
Collecting duct
1200
1200
1200
Small volume of
Urea contributes to concentrated urine
the osmotic gradient.
ADH increases its
recycling.
105
Urea Recycling and the
Medullary Osmotic Gradient
• Urea helps form medullary gradient
• Enters filtrate in ascending thin limb of nephron loop by
facilitated diffusion
• Cortical collecting duct reabsorbs water; leaves urea
• In deep medullary region now highly concentrated urea 
interstitial fluid of medulla  back to ascending thin limb  high
osmolality in medulla
106
Diuretics
• Chemicals that enhance urinary output
• ADH inhibitors, e.g., alcohol
• Na+ reabsorption inhibitors (and resultant H2O reabsorption),
e.g., caffeine, drugs for hypertension or edema
• Loop diuretics inhibit medullary gradient formation
• Osmotic diuretics - substance not reabsorbed so water remains in
urine, e.g., high glucose of diabetic patient
107
Clinical Evaluation of Kidney
Function
• Urine examined for signs of disease
• Assessing renal function requires both blood and urine
examination
108
Renal Clearance
• Volume of plasma kidneys clear of particular substance in
given time
• Renal clearance tests used to determine GFR
• To detect glomerular damage
• To follow progress of renal disease
109
Renal Clearance
• C = UV/P
•
•
•
•
C = renal clearance rate (ml/min)
U = concentration (mg/ml) of substance in urine
V = flow rate of urine formation (ml/min)
P = concentration of same substance in plasma
110
Renal Clearance
• Inulin (plant polysaccharide) is standard used
• Freely filtered; neither reabsorbed nor secreted by
kidneys; its renal clearance = GFR = 125 ml/min
• If C < 125 ml/min, substance reabsorbed
• If C = 0, substance completely reabsorbed, or not
filtered
• If C = 125 ml/min, no net reabsorption or
secretion
• If C > 125 ml/min, substance secreted (most drug
metabolites)
111
Homeostatic Imbalance
• Chronic renal disease - GFR < 60 ml/min for 3 months
• E.g., in diabetes mellitus; hypertension
• Renal failure – GFR < 15 ml/min
• Causes uremia syndrome – ionic and hormonal imbalances;
metabolic abnormalities; toxic molecule accumulation
• Treated with hemodialysis or transplant
112
Physical Characteristics of
Urine
• Color and transparency
• Clear
• Cloudy may indicate urinary tract infection
• Pale to deep yellow from urochrome
• Pigment from hemoglobin breakdown; more concentrated urine 
deeper color
• Abnormal color (pink, brown, smoky)
• Food ingestion, bile pigments, blood, drugs
113
Physical Characteristics of
Urine
• Odor
• Slightly aromatic when fresh
• Develops ammonia odor upon standing
• As bacteria metabolize solutes
• May be altered by some drugs and vegetables
114
Physical Characteristics of
Urine
• pH
• Slightly acidic (~pH 6, with range of 4.5 to 8.0)
• Acidic diet (protein, whole wheat)   pH
• Alkaline diet (vegetarian), prolonged vomiting, or urinary tract
infections  pH
• Specific gravity
• 1.001 to 1.035; dependent on solute concentration
115
Chemical Composition of Urine
• 95% water and 5% solutes
• Nitrogenous wastes
• Urea (from amino acid breakdown) – largest solute component
• Uric acid (from nucleic acid metabolism)
• Creatinine (metabolite of creatine phosphate)
116
Chemical Composition of Urine
• Other normal solutes
• Na+, K+, PO43–, and SO42–, Ca2+, Mg2+ and HCO3–
• Abnormally high concentrations of any constituent, or
abnormal components, e.g., blood proteins, WBCs, bile
pigments, may indicate pathology
117
OBJECTIVES:
Urine Transport, Storage, and Elimination
14. Describe the general location, structure, and function of the ureters.
15. Describe the general location, structure, and function of the urinary bladder.
16. Describe the general location, structure, and function of the urethra.
17. Compare the course, length, and functions of the male urethra with those of
the female.
18. Define micturition and describe its neural control.
118
Urine transport, Storage, and
Elimination: Ureters
• Convey urine from kidneys to bladder
• Begin at L2 as continuation of renal pelvis
• Retroperitoneal
• Enter base of bladder through posterior wall
• As bladder pressure increases, distal ends of ureters close,
preventing backflow of urine
119
Ureters
• Three layers of ureter wall from inside out
• Mucosa - transitional epithelium
• Muscularis – smooth muscle sheets
• Contracts in response to stretch
• Propels urine into bladder
• Adventitia – outer fibrous connective tissue
120
Figure 25.19 Cross-sectionalview of the ureter wall (10x).
Lumen
Mucosa
• Transitional
epithelium
• Lamina
propria
Muscularis
• Longitudinal
Layer
• Circular
layer
Adventitia
121
Homeostatic Imbalance
• Renal calculi - kidney stones in renal pelvis
• Crystallized calcium, magnesium, or uric acid salts
• Large stones block ureter  pressure & pain
• May be due to chronic bacterial infection, urine retention,
Ca2+ in blood, pH of urine
• Treatment - shock wave lithotripsy – noninvasive; shock waves
shatter calculi
122
Urinary Bladder
• Muscular sac for temporary storage of urine
• Retroperitoneal, on pelvic floor posterior to pubic symphysis
• Males—prostate gland inferior to bladder neck
• Females—anterior to vagina and uterus
123
Urinary Bladder
• Openings for ureters and urethra
• Trigone
• Smooth triangular area outlined by openings for ureters and
urethra
• Infections tend to persist in this region
124
Urinary Bladder
• Layers of bladder wall
• Mucosa - transitional epithelial mucosa
• Thick detrusor muscle - three layers of smooth muscle
• Fibrous adventitia (peritoneum on superior surface only)
125
Urinary Bladder
• Collapses when empty; rugae appear
• Expands and rises superiorly during filling without significant
rise in internal pressure
• ~ Full bladder 12 cm long; holds ~ 500 ml
• Can hold ~ twice that if necessary
• Can burst if overdistended
126
Figure 25.18 Pyelogram.
Kidney
Renal
pelvis
Ureter
Urinary
bladder
127
Figure 25.20a Structureof the urinary bladder and urethra.
Peritoneum
Ureter
Rugae
Detrusor
Adventitia
Ureteric orifices
Trigone of bladder
Bladder neck
Internal urethral sphincter
Prostate
Prostatic urethra
Intermediate part of the urethra
External urethral sphincter
Urogenital diaphragm
Spongy urethra
Erectile tissue of penis
External urethral orifice
Male. The long male urethra has three regions:
prostatic, intermediate, and spongy.
128
Figure 25.20b Structureof the urinary bladder and urethra.
Peritoneum
Ureter
Rugae
Detrusor
Ureteric orifices
Bladder neck
Internal urethral
sphincter
Trigone
External urethral
sphincter
Urogenital diaphragm
Urethra
External urethral
orifice
Female.
129
Urethra
• Muscular tube draining urinary bladder
• Lining epithelium
• Mostly pseudostratified columnar epithelium, except
• Transitional epithelium near bladder
• Stratified squamous epithelium near external urethral orifice
130
Urethra
• Sphincters
• Internal urethral sphincter
• Involuntary (smooth muscle) at bladder-urethra junction
• Contracts to open
• External urethral sphincter
• Voluntary (skeletal) muscle surrounding urethra as it passes through
pelvic floor
131
Urethra
• Female urethra (3–4 cm)
• Tightly bound to anterior vaginal wall
• External urethral orifice
• Anterior to vaginal opening; posterior to clitoris
132
Figure 25.20b Structureof the urinary bladder and urethra.
Peritoneum
Ureter
Rugae
Detrusor
Ureteric orifices
Bladder neck
Internal urethral
sphincter
Trigone
External urethral
sphincter
Urogenital diaphragm
Urethra
External urethral
orifice
Female.
133
Urethra
• Male urethra carries semen and urine
• Three named regions
• Prostatic urethra (2.5 cm)—within prostate gland
• Intermediate part of the urethra (membranous urethra) (2 cm)—
passes through urogenital diaphragm from prostate to beginning of
penis
• Spongy urethra (15 cm)—passes through penis; opens via external
urethral orifice
134
Figure 25.20a Structureof the urinary bladder and urethra.
Peritoneum
Ureter
Rugae
Detrusor
Adventitia
Ureteric orifices
Trigone of bladder
Bladder neck
Internal urethral sphincter
Prostate
Prostatic urethra
Intermediate part of the urethra
External urethral sphincter
Urogenital diaphragm
Spongy urethra
Erectile tissue of penis
External urethral orifice
Male. The long male urethra has three regions:
prostatic, intermediate, and spongy.
135
Micturition
• Urination or voiding
• Three simultaneous events must occur
• Contraction of detrusor muscle by ANS
• Opening of internal urethral sphincter by ANS
• Opening of external urethral sphincter by somatic nervous system
136
Micturition
• Reflexive urination (urination in infants)
• Distension of bladder activates stretch receptors
• Excitation of parasympathetic neurons in reflex center in sacral
region of spinal cord
• Contraction of detrusor muscle
• Contraction (opening) of internal sphincter
• Inhibition of somatic pathways to external sphincter, allowing its
relaxation (opening)
137
Micturition
• Pontine control centers mature between ages 2 and 3
• Pontine storage center inhibits micturition
• Inhibits parasympathetic pathways
• Excites sympathetic and somatic efferent pathways
• Pontine micturition center promotes micturition
• Excites parasympathetic pathways
• Inhibits sympathetic and somatic efferent pathways
138
Figure 25.21 Controlof micturition.
Brain
Higher brain
centers
Urinary bladder
fills, stretching
bladder wall
Allow or inhibit micturition
as appropriate
Pontine micturition
center
Afferent impulses
from stretch
receptors
Inhibits micturition by
acting on all three
Spinal efferents
Promotes micturition
by acting on all three
spinal efferents
Simple
spinal
reflex
Pontine storage
center
Spinal
cord
Spinal
cord
Parasympathetic
activity
Sympathetic
activity
Detrusor contracts;
internal urethral
sphincter opens
Somatic motor
nerve activity
Parasympathetic activity
Sympathetic activity
Somatic motor nerve activity
External urethral
sphincter opens
Micturition
Inhibits
139
Homeostatic Imbalance
• Incontinence usually from weakened pelvic muscles
• Stress incontinence
• Increased intra-abdominal pressure forces urine through external
sphincter
• Overflow incontinence
• Urine dribbles when bladder overfills
140
Homeostatic Imbalance
• Urinary retention
•
•
•
•
Bladder unable to expel urine
Common after general anesthesia
Hypertrophy of prostate
Treatment - catheterization
141
Homeostatic Imbalance
• Polycystic kidney disease
• Many fluid-filled cysts interfere with function
• Autosomal dominant form – less severe but more common
• Autosomal recessive – more severe
• Cause unknown but involves defect in signaling proteins
142
Developmental Aspects
• Frequent micturition in infants due to
small bladders and less-concentrated urine
• Incontinence normal in infants: control of
voluntary urethral sphincter develops with
nervous system
• E. coli bacteria account for 80% of all
urinary tract infections
• Untreated childhood streptococcal
infections may cause long-term renal
damage
• Sexually transmitted diseases can also
inflame urinary tract
143
Developmental Aspects
• Most elderly people have abnormal kidneys histologically
• Kidneys shrink; nephrons decrease in size and number; tubule
cells less efficient
• GFR ½ that of young adult by age 80
• Possible from atherosclerosis of renal arteries
• Bladder shrinks; loss of bladder tone  nocturia and
incontinence
144