Urinary System I: Kidneys and Urine Formation

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Urinary System I: Kidneys and Urine Formation
 Functions of the Urinary System
 Organs of the Urinary System
 The Kidney
• Coverings and Regions
• Blood Flow
• Nephrons: Glomeruli and Renal
Tubules
• Urine Formation
 Urinalysis
 Ureters, Bladder, and Urethra
Functions of the Urinary System: Blood Filtration
 Elimination of waste products
• Nitrogenous wastes (amino groups from amino acids)
• Toxins
• Drugs
 Regulate aspects of homeostasis
• Water balance
• Electrolytes
• Acid-base balance in the blood
• Blood pressure
• Red blood cell production (erythropoietin)
• Activation of vitamin D
Organs of the Urinary system
 Kidneys
• Against the dorsal body wall
• At the level of T12 to L3
• The right kidney is slightly
lower than the left
• Retroperitoneal (posterior to
and outside of parietal
peritoneum)
• Attached to ureters, renal blood
vessels, and nerves at renal
hilus
• Covered with adipose
 Ureters
 Urinary bladder
 Urethra
Coverings of the Kidneys
 Renal capsule
• Surrounds each kidney
 Adipose capsule
 Fascia layer/adventitia
(connective tissue) substitutes
for serosae outside of
peritoneal cavity
• Surrounds the kidney
• Provides protection to the
kidney
• Helps keep the kidney in
its correct location
Regions of the Kidney
 Kidney Regions
• Renal cortex – outer region
• Renal medulla – inside the
cortex
• Renal pelvis – inner
collecting tube
 Kidney Structures
• Medullary pyramids –
triangular regions of tissue
in the medulla
• Renal columns –
extensions of cortex-like
material inward
• Calyces – cup-shaped
structures that funnel urine
towards the renal pelvis
Blood Flow in the Kidneys
Glomerular capillaries
Peritubular
capillaries
Unique: Incoming vessels
enter as an arteriole,
narrow into a capillary
bed in the glomerulus,
leave in an arteriole, and
then break into the
peritubular capillary
bed before leaving as
venus blood.
The Nephron
Glomerulus and Bowman’s Capsule

A specialized capillary bed

Attached to narrow arterioles on
both sides (maintains high
pressure in capsule)

Fenestrated glomerular
endothelium
•

Allows filtrate to pass from
plasma into the glomerular
capsule
Filtration
slits
Layers of Bowman’s capsule
•
•
Parietal layer: simple
squamous epithelium
Visceral layer: branching
epithelial podocytes
o
Extensions
terminate in foot
processes that cling
to basement
membrane
o
Filtration slits
allow filtrate to
pass into the
capsular space
Capsular
space
Renal Tubule
 Proximal
convoluted tubule
 Loop of Henle
 Distal convoluted
tubule
 Collecting duct
Figure 15.3b
Two Types of Nephrons
 Cortical nephrons
• Located entirely in
the cortex
• Includes most
nephrons (> 85%)
Cortex
 Juxtamedullary
nephrons
• Found at the
boundary of the
cortex and medulla
• Important in the
production of
concentrated urine
Medulla
Juxtaglomerular Apparatus (JGA)



Macula densa: sensors of the filtrate
•
Tall, closely packed cells lining the ascending Lof H or PCT
•
Water and NaCl concentration detected by osmo -and
chemoreceptors
•
If ↓filtrate water volume, then stimulation of renin release by
JG, ↑blood water volume , ↑blood pressure .
•
If ↓NaCl in PCT filtrate; ↑dilation of afferent arteriole 
↓reduce filtration rate, ↑Na + stays in filtrate by tubules,
↑blood Na+ ,
•
If ↑NaCl in PCT filtrate; then ↑renin release by JG, ↑blood
water volume , ↑blood pressure .
Granular cells (juxtaglomerular, or JG cells): pressure sensors of
incoming blood and storage of renin
•
Enlarged, smooth muscle cells of blood afferent arteriole
•
Secretory granules release renin when epi & NE in blood
•
Act as mechanoreceptors that sense low blood pressure
•
Responds to stimuli by macula densa
Extraglomerular mesangial cells
Peritubular Capillaries

Arise from efferent arteriole of
the glomerulus

Cling to adjacent renal tubules in
cortex

Low-pressure, porous capillaries
adapted for absorption

Reabsorb (reclaim) some
substances from collecting tubes

Empty into venules

Vasa recta are the long vessels
parallel to long loops of Henle
Filtrate
efferent afferent
arterioles
Water is
reclaimed
from filtrate
into venous
circulation
via
peritubular
capillaries
Epithelia in the Tubules Are Designed for Filtration and Absorption
Glomerular capsule: parietal layer
Renal cortex
Renal medulla
Basement
membrane
Renal corpuscle
• Glomerular capsule
• Glomerulus
Renal pelvis
Ureter
Podocyte
Distal
convoluted
tubule
Kidney
Fenestrated
endothelium
of the glomerulus
Glomerular capsule: visceral layer
Microvilli
Mitochondria
Proximal
convoluted
tubule
Highly infolded plasma
membrane
Proximal convoluted tubule cells
Cortex
and thick
ascending
L 0f H
Medulla
Thick segment
Thin segment
Loop of Henle
• Descending limb
• Ascending limb
Distal convoluted tubule cells
Collecting
duct
Loop of Henle (thin-segment) cells
Principal cell
Mostly cuboidal epithelium with modifications in membrane surfaces
Intercalated cell
Collecting duct cells
Figure 25.5
Urine Formation Processes
 A. Filtration
•
Nonselective passive process
•
Water and solutes smaller than proteins are forced
through capillary walls, no cells - essentially plasma
•
Filtrate is collected in the glomerular capsule and leaves
via the renal tubule
•
Blood pressure relatively high in glomerulus
•
Efficient filtration driven by hydrostatic pressure
 B. Tubular Reabsorption
•
The peritubular capillaries reabsorb several materials:
H2O, glucose, amino acids, ions
•
Some reabsorption is passive, most is active
•
Nitrogenous waste products not reabsorbed, nor excess
water, urea, uric acid, or creatinine
•
Most reabsorption occurs in the proximal convoluted
tubule
 C. Tubular Secretion
•
Some materials pumped from the peritubular capillaries
into the renal tubules: H+, K+, creatinine
•
Materials left in the renal tubule move toward the ureter
Net Filtration Pressure (NFP) at the Glomerulus
Afferent
arteriole
Glomerular
capsule
NFP = HPg – (OPg + HPc)
= (push outwards - back pressure inwards)
10
mm
Hg
Net
filtration
pressure
Glomerular (blood) hydrostatic pressure
(HPg = 55 mm Hg)
Blood colloid osmotic pressure
(Opg = 30 mm Hg)
Capsular hydrostatic pressure
(HPc = 15 mm Hg)
Figure 25.11
Glomerular Filtration Rate
 Volume of filtrate formed per minute by the
kidneys (120–125 ml/min)
 Governed by (and directly proportional to)
• Total surface area available for filtration
• Filtration membrane permeability
• Flow rate (GFR) is tightly controlled by two
types of mechanisms
o Intrinsic controls (renal autoregulation)
o Extrinsic controls (nervous and endocrine regulation
Intrinsic Controls (Renal Autoregulation) of GFR
 Local action within the kidney
• Myogenic mechanism
o
 BP  constriction of afferent arterioles
 Helps maintain normal GFR
 Protects glomeruli from damaging high BP
o
 BP  dilation of afferent arterioles
 Helps maintain normal GFR
• Tubuloglomerular feedback mechanism, which senses changes in
the juxtaglomerular apparatus
o
Flow-dependent mechanism directed by the macula densa cells
o
If GFR increases, filtrate flow rate increases in the tubule
o
Filtrate NaCl concentration will be high because of insufficient time for
reabsorption
o
Macula densa cells of the JGA respond to NaCl by releasing a
vasoconstricting chemical that acts on the afferent arteriole   GFR
Extrinsic controls of GFR
 Nervous and endocrine mechanisms that maintain
blood pressure, but affect kidney function
 Under normal conditions at rest
• Renal blood vessels are dilated
• Renal autoregulation mechanisms prevail
 Under extreme stress
• Norepinephrine is released by the sympathetic nervous
system; epinephrine is released by the adrenal medulla
• NE and Epi cause constriction of afferent arterioles,
inhibiting filtration and triggering the release of renin
from JGA cells leading to renin-angiotensin cascade
Extrinsic Controls: Renin-Angiotensin Mechanism
 Triggered when the granular cells of the JGA
release renin
angiotensinogen (a plasma globulin)
renin 
angiotensin I
angiotensin converting
enzyme (ACE) 
angiotensin II
Effects of Angiotensin II
1.
Constricts arteriolar smooth muscle, causing mean arterial
pressure to rise (hypertensive)
2.
Stimulates the reabsorption of Na+
•
Acts directly on the renal tubules
•
Triggers adrenal cortex to release aldosterone
(hypertensive
3.
Stimulates the hypothalamus to release ADH and activates
the thirst center (increases hydration)
4.
Constricts efferent arterioles, decreasing peritubular capillary
hydrostatic pressure and increasing fluid reabsorption (saves
water)
5.
Causes glomerular mesangial cells to contract, decreasing the
surface area available for filtration (saving water)
Extrinsic Controls: Renin-Angiotensin Mechanism
 Triggers for renin release by granular cells
• Reduced stretch of granular cells (MAP
below 80 mm Hg)
• Stimulation of the granular cells by
activated macula densa cells
• Direct stimulation of granular cells via 1adrenergic receptors by renal nerves
SYSTEMIC BLOOD PRESSURE
(–)
Blood pressure in
afferent arterioles; GFR
Baroreceptors in
blood vessels of
systemic circulation
Granular cells of
juxtaglomerular
apparatus of kidney
GFR
Release
Stretch of smooth
muscle in walls of
afferent arterioles
Filtrate flow and
NaCl in ascending
limb of Henle’s loop
Targets
Vasodilation of
afferent arterioles
(+)
(+)
Sympathetic
nervous system
Catalyzes cascade
resulting in conversion
Angiotensinogen
(+)
Macula densa cells
of JG apparatus
of kidney
(+)
Renin
Angiotensin II
(+)
Adrenal cortex
Systemic arterioles
(+)
Releases
Aldosterone
Release of vasoactive
chemical inhibited
Vasoconstriction;
peripheral resistance
Targets
Kidney tubules
Vasodilation of
afferent arterioles
Na+ reabsorption;
water follows
GFR
(+) Stimulates
(–) Inhibits
Increase
Decrease
Blood volume
Systemic
blood pressure
Myogenic mechanism
of autoregulation
Tubuloglomerular
mechanism of
autoregulation
Intrinsic mechanisms directly regulate GFR despite
moderate changes in blood pressure (between 80
and 180 mm Hg mean arterial pressure).
Hormonal (renin-angiotensin)
mechanism
Neural controls
Extrinsic mechanisms indirectly regulate GFR
by maintaining systemic blood pressure, which
drives filtration in the kidneys.
Figure 25.12
Urine Formation Processes
 A. Filtration
•
Nonselective passive process
•
Water and solutes smaller than proteins are forced
through capillary walls, no cells - essentially plasma
•
Filtrate is collected in the glomerular capsule and leaves
via the renal tubule
•
Blood pressure relatively high in glomerulus
•
Efficient filtration driven by hydrostatic pressure
 B. Tubular Reabsorption
•
The peritubular capillaries reabsorb several materials:
H2O, glucose, amino acids, ions
•
Some reabsorption is passive, most is active
•
Nitrogenous waste products not reabsorbed, nor excess
water, urea, uric acid, or creatinine
•
Most reabsorption occurs in the proximal convoluted
tubule
 C. Tubular Secretion
•
Some materials pumped from the peritubular capillaries
into the renal tubules: H+, K+, creatinine
•
Materials left in the renal tubule move toward the ureter
Mechanism of Urine Formation
Hormone regulated
reabsorption of
Ca2+ ( by PTH),
water ( ADH)
Na+ ( aldosterone
and ANP)
Most reabsorption
occurs here
In general:
 ADH
 Concentrated urine
 Water conservation
--------------- Aldosterone (often
triggered by  Angiotensin II)
H2O
 Dilute urine
 Na+ conservation
 Blood pressure
 Urea reabs.
with  ADH
Reduces the volume and
saltiness of the filtrate
Na+, K+
resabsorbed
Countercurrent Mechanism
 Occurs when fluid flows in opposite directions in
two adjacent segments of the same tube
• E.g. Filtrate flow in the loop of Henle
(countercurrent multiplier)
• E.g. Blood flow in the vasa recta (countercurrent
exchanger)
 Role of countercurrent mechanisms
• Establish and maintain an osmotic gradient
• Allow the kidneys to vary urine concentration
(but especially make dilute urine)
• Allow for more efficient exchange of ions or gases
Countercurrent Multiplier: Loop of Henle
 Descending limb
• Freely permeable to H2O, which
passes out of the filtrate into the
hyperosmotic medullary interstitial
fluid
• Filtrate osmolality increases to
~1200 mOsm
 Ascending limb
• Impermeable to H2O
• Selectively permeable to solutes
o Na+ and Cl– are passively
reabsorbed in the thin segment,
actively reabsorbed in the thick
segment
• Filtrate osmolarity decreases to
100 mOsm
Countercurrent in Loop of Henle Extracts Water then Salt
Osmolality
of interstitial
fluid
(mOsm)
Active transport
H2O
NaCI
H2O
NaCI
H2O
NaCI
H2O
NaCI
Cortex
Passive transport
Water impermeable
The salty outer medulla created by the
ascending loop amplifies the extraction of
water in the descending loop. Without
countercurrent, much less water would be
removed and therefore would be less
efficient.
Outer
medulla
H2O
NaCI
H2O
H2O
Inner
medulla
Loop of Henle
Renal function online
animation
(a) Countercurrent multiplier.
The long loops of Henle of the
juxtamedullary nephrons
create the medullary
osmotic gradient.
Figure 25.16a
Countercurrent Exchanger: Vasa Recta
 The Vasa Recta (peritubular
capillaries parallel to the Loop
of Henle
• Maintain the osmotic
gradient
• Deliver blood to the
medullary tissues
• Protect the medullary
osmotic gradient by
preventing rapid removal
of salt, and by removing
reabsorbed H2O
Countercurrent in Loop of Henle Peritubular Capillaries Maintains Salt Gradient
Osmolality
of interstitial
fluid
(mOsm)
Cortex
The saltier cortex
created by the
ascending vasa recta
peritubular capillaries
amplifies the extraction
of water in the
descending loop.
Without
countercurrent, much
less would remain in
the blood.
Blood from
efferent
arteriole
Passive transport
To vein
NaCI
H2O
NaCI
H2O
NaCI
H2O
NaCI
H2O
Outer
medulla
NaCI
H2O
NaCI
H2O
NaCI
H2O
NaCI
H2O
Online kidney
physiology
animation
Inner
medulla
Vasa recta
(b) Countercurrent exchanger.
The vasa recta preserves the
medullary gradient while
removing reabsorbed water
and solutes.
Figure 25.16b
Urea Recycling
 Urea moves between the collecting ducts and
the loop of Henle
• Secreted into filtrate by facilitated
diffusion in the ascending thin segment
• Reabsorbed by facilitated diffusion in the
collecting ducts deep in the medulla
• More collecting duct reabsorption if ADH
present
 Contributes to the high osmolality in the
medulla
Diuretics
 Chemicals that enhance the urinary output
• Osmotic diuretics: substances not
reabsorbed, (e.g., high glucose in a
diabetic patient) causes increased water
and urine volume
• ADH inhibitors such as alcohol
• Substances that inhibit Na+ reabsorption
and obligatory H2O reabsorption such
as caffeine and many drugs
Kidney Dialysis
Continuous ambulatory peritoneal dialysis (CAPD)
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