Ch 26: The Urinary System
Summary of Kidney functions:
•  Kidneys regulate Blood…
–  Volume : conserve / eliminate H2O
–  Pressure : secrete Renin enzyme
–  Osmolarity : keep a constant 300
milliosmoles of solute/L
–  Ions: Na+, K+, Ca2+, Cl-, HPO42–  pH : excrete H+, conserve HCO3–  Glucose: can do gluconeogenesis
•  Kidney, Ureters,
Bladder, Urethra
•  scientific study of
above: Nephrology
•  branch of medicine:
Urology
•  medical specialist:
Urologist
Kidney size & location
•  Produce 2 hormones…
–  Calcitrol (active Vit D)
–  Erythropoietin (RBC production)
•  Excrete wastes from…
–  metabolic reactions: urea,
ammonia, bilirubin, creatinine, uric
acid
–  foreign substances: drugs,
medicines, environmental toxins
Renal Cortex & Medulla
•
•
‘Parenchyma’means functional
part of any organ. For kidney:
renal cortex + renal pyramids
RENAL CORTEX includes:
–  Outer, Cortical zone
–  Inner, Juxtamedullary zone
–  Renal columns are bits of the
cortex that extend between renal
pyramids
•
•  Size: 5-7cm x 10-13 cm, Mass: 130-140g
•  Location: above the waist from T12 - L3 w R kidney slightly lower
because of liver.
•  Retroperitoneal ie behind the peritoneum, the sac which contains
the abdominal organs. Lie between peritoneum and posterior
abdominal wall
RENAL MEDULLA
–  Renal pyramids: 8-18, coneshaped
•
•
•
Base faces cortex
Apex /‘renal papilla’ points
toward hilum
1 RENAL LOBE = 1 renal pyramid
+ overlying cortex area + ½ of
each adjacent renal column
1
Renal Arteries
•  Segmental arteries branch
into interlobar arteries.
•  These divide at the arcs at
the top of pyramids into
arcuate arteries.
•  Blood enters the kidneys via R & L Renal Arteries
•  Kidneys receive 20-25% of resting cardiac output.
•  The renal arteries branch into segmental arteries.
•  Arcuate arteries divide into
interlobular arteries
Urine Formation & Drainage
Afferent &
Efferent
Arterioles
• The Afferent arteriole
divides into a specialized
ball of Glomerular
Capillaries
• Glomerular capillaries
reunite to form the
Efferent Arteriole.
• The Efferent arteriole
then divides to form
Peritubular Capillaries
• Peritubular capillaries
unite to form interlobular
veins
•
•
•
•
•
•
•
Nephron: Formation of urine. Functional unit of kidney.
Papillary Ducts: hole for urine to drain out of medullary papilla
Minor Calyces (8-18) collect from each renal pyramid
Major Calyces (2-3)
Renal pelvis - Urine exits kidney
Ureters connect and empty into Urinary Bladder
Urethra - Urine exits body
2
Glomeruli are covered by a capsule
Glomerulus & Bowman’s Capsule
RENAL CORPUSCLE
Bowman’s Capsule
•  A glomerulus is a ball of fenestrated capillaries.
•  Each glomerulus is covered by a double-walled capsule called Bowman’s
Capsule. It is the first part of the nephron
•  Together, glomerulus + bowman’s capsule are called a Renal Corpuscle
•  There are 1 million glomeruli per kidney
Glomerular Filtration Membrane Structure
The leaky filtration membrane is made of
3 layers:
•
•
•
Bowman’s capsule has a visceral and parietal layer.
The visceral layer of bowman’s capsule is made of Podocyte cells.
The plasma, along with its solutes, is forced out of the glomerular capillaries and
through podocytes that surround them to enter the subcapsular (urinary) space
1.  Fenestrations of glomerular capillaries
2.  Basal lamina
3.  Filtration slits between the podocyte’s
pedicels
3
Glomerular Membrane Permeability
YES: Permits filtration of PLASMA
—  water
—  glucose
—  vitamins
—  amino acids
—  very small plasma proteins
—  ammonia & urea
—  Ions (Na, Cl, K, HCO3)
NO: Prevents filtration of
—  most plasma proteins
(*Albumin is too large to
easily pass through the
slits)
—  blood cells
GFR
GLOMERULAR FILTRATION
—  platelets
Step 1:
Glomerular
FILTRATION
Net Filtration
Pressure
PRESSURE THAT
PROMOTES FILTRATION:
1.
GLOMERULAR BLOOD
HYDROSTATIC PRESSURE:
blood pressure in glomerular
capillaries forces water and
solutes out of filtration slits
(55mmHg)
PRESSURES THAT
OPPOSE FILTRATION:
•  Blood Pressure forces plasma fluids and solutes out
through the membrane. This is called FILTRATION
1.
CAPSULAR HYDROSTATIC
PRESSURE: pressure from fluid
already in capsule (15mmHg)
2.
BLOOD COLLOID OSMOTIC
PRESSURE: proteins in plasma
(30mmHg)
NET FILTRATION PRESSURE
GBHP - (CHP + BCOP) =
55mmHg -(15+30)= 10mmHg
Glomerular filtrate: fluid that
enters bowman’s capsule
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*Glomerular Filtration Rate (GFR )
•  Glomerular Filtration Rate: amount
of filtrate formed by all renal
corpuscles of both kidneys per
minute
•  The GFR depends on the net
filtration pressure
•  Kidneys must maintain a
relatively constant GFR.
•  Normal GFR:
•  125ml/min in males
•  105ml/min in females
–  If GFR is too high – good solutes
pass through tubules too quickly so
they are lost or not reabsorbed
125mL/min
Hormonal, Neural and Local
REGULATION OF GFR
–  If GFR is too low – nearly all
solutes, including wastes, are
reabsorbed so waste is not
adequately excreted
GFR Regulation
•  GFR is regulated in 3 ways:
Renal Autoregulation of GFR
Everyday changes in BP are
regulated by 2 mechanisms:
1.
1.  Renal Autoregulation (By the kidney itself)
–  Macula Densa
–  Afferent & Efferent Arterioles
–  Mesangial Cells
2.
•  Sympathetic Nervous system (Norepinephrine)
3.  By hormones
•  Renin-Angiotensin (RA)
•  Atrial Natriuretic Peptide (ANP)
If BP rises, it stretches the smooth
muscle of Afferent Arteriole, which
reflexively constricts to ↓GFR
Or
•
If BP drops the smooth muscle of
the Afferent Arteriole dilates, or
reflexively relaxes, allows more
blood in, which raises GFR
•  Myogenic mechanism of the arterioles
•  Tubuloglomerular feedback in the Juxtaglomerular apparatus
2.  By the nervous system
Myogenic mechanism
•
TubuloGlomerular feedback
•
•
•
•
Macula Densa receptors detect↑
NaCl
If BP is too high, GFR is
increased & solutes cannot be
reabsorbed. so filtrate NaCl ↑
ie↑NaCl=↑GFR
Macula Densa sends signals to
surrounding cells to constrict
afferent arterioles, which
reduces GFR
5
Renal Autoregulation:
MESANGIAL CELLS
•
Intraglomerular Mesangial
cells are contractile cells
located among the podocytes
and glomerular capillaries.
•
Their surface is stuck to part
of the basement membrane of
the capillaries
Sympathetic Regulation of GFR (NE & α1)
–  When they contract:
•  they tug on the capillary
basement membrane
•  This reduces capillary
diameter/ surface area
•  GFR decreases
–  When they are relaxed,
as with ANP:
•  Capillary diameter/
surface area increases
•  GFR increases
Neural (NE) Regulation of GFR
At rest, the Afferent and Efferent arterioles are dilated & GFR is normal
–
–
–
–
Under stress, when Sympathetic nerves are stimulated,
Renal Vasomotor Nerves secrete Norepinephrine.
NE binds to α1 receptors on arterioles & they constrict.
GFR will decrease.
Hormonal: Renin è Angiotensin increases GFR
•
•
Low GFR causes Renin release
•
Low peripheral Blood Pressure
causes low GFR
•
Low GFR leads to low NaCl
detected by Macula Densa
•
Granular, or Juxtaglomerular
cells in JGA release renin
Renin raises both BP & GFR
•
•
•  Under Moderate stress, ↑NE:
•  Afferent: moderate constriction, Efferent: moderate constriction
•  GFR is slightly decreased
•
Renin cleaves
Angiotensinogen into
Angiotensin I.
Angiotensin II constricts all
peripheral arterioles and the
efferent arterioles
thus renin & angiotensin raises
peripheral BP & restores GFR
•  Great stress (eg intense exercise, hemorrhage) ↑↑ NE :
•
•
•
•
Afferent: very constricted, Efferent: less constricted
GFR is greatly decreased
urine output is decreased to conserve blood volume
Blood must flow to other, more critical, tissues
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ANP increases GFR
•  Increased blood volume
stretches the atria of the
heart which then secrete
ANP
•  ANP relaxes mesangial
cells.
•  increased glomerular
capillary surface area
increases GFR
•  More filtrate is produced/
min. plasma (blood
volume) levels reduce
GFR Regulation Summary
Regulatory
Mechanism
Effect
on GFR
Triggered By
Corrective Mechanism
Myogenic
mechanism
↓ or ↑
stretch or slack in
afferent arteriole
Reflexive relaxation or
contraction of smooth
mm
Tubuloglomerular
feedback
↓
Increased NaCl
(GFR) around
macula densa
Reduce NO production
by macula densa
Sympathetic
Nerves (NE)
↓
Exercise, shock,
stress
Vasoconstriction of
afferent arterioles.
Reduce blood to kidney
ReninAngiotensin
↑
Low NaCl (GFR)
around macula
densa
Renin is released from
granular cells
Atrial Natriuretic ↑
Peptide
High blood
pressure in heart
Relax mesangial cells.
Increase capillary sa
Parts of the Nephron
•  Bowman’s Capsule
•  Proximal Convoluted
Tubule (PCT)
From nephron back into blood
REABSORPTION
•  Descending Loop of
Henle
•  Ascending Loop of Henle
•  Distal Convoluted Tubule
(DCT) with Macula Densa
•  Collecting Duct
7
Step 2: PCT & Reabsorption
Substances FILTERED at the glomerulus
*notice that 0 CreaTINine is reabsorbed
•  The Proximal Convoluted Tubule (PCT) epithelial cells are the
main site of reabsorption
•  Reabsorption: 65% of water & useful substances that were
filtered out at the glomerulus are returned to the blood
Reabsorption of Solutes in PCT
Water reabsorbed into blood
•  All water reabsorption into the
blood occurs via osmosis paracellular & transcellular
aided by aquaporin-1 water
channels
Solutes are reabsorbed into the blood from the tubules by 2 routes:
1.  Paracellular: 50% Between PCT cells. Passive route/ diffusion.
2.  Transcellular: Through PCT cells
–  Solutes are pumped across the tubule membrane by active transport.
–  Na is the most abundant ion in the filtrate & is actively pumped out the
basolateral side of the epithelial cell. This keeps Na low within the PCT cell
–  Most 2˚ active transport mechanisms are then powered by Na+ gradient
•
•  Solute reabsorption creates
an osmotic gradient that
drives H2O reabsorption
•  Obligatory water
reabsorption: water must
follow the solutes out of the
tubules
Na Symport: Glucose, AAs, lactic acid, water-soluble vitamins, phosphate, sulfate
8
FYI -Transport Maximum & Glycosuria
Reabsorption – blood takes back the good stuff
•  Transport maximum (Tm): Upper limit to how fast transporter proteins
can work mg/min
•  When blood concentration of glucose is above 200 mg/ml, the renal
symporters are “all full”. They cannot work fast enough to reabsorb
any more glucose that enters the glomerular filtrate.
•  So…Some of the glucose exits in the urine (glycosuria)
•  Diabetes mellitus is the most common cause of glycosuria
Secretion of Waste from blood into Filtrate
•  Secretion: unwanted
material from the blood is
transferred into tubular fluid
(urine) by active transport
From blood to nephron
SECRETION
•  Unwanted materials:
–  K+
–  H+ (reduces blood
acidity)
–  Urea
–  NH4+ (ammonium)
–  Drugs
•  Helps eliminate waste
substances from the
body
9
pH balance
& the kidney
Distal Convoluted Tubule
•  CO2, both from the filtrate, and
interstitial fluid, diffuses into
proximal tubular epithelial cells.
•  Carbonic Anhydrase in PCT
cells converts CO2 to carbonic
acid, then to bicarb HCO3- & H+
•  Bicarb (HCO3-) is
reabsorbed, while…
•  hydrogen ions (H+) are
secreted.
•  This one mechanism that
keeps blood from becoming
too acidic
Late DCT
•  Reabsorption:
Early DCT reabsorbs:
–  Na, Cl
–  *Ca2+ if Parathyroid
hormone (PTH) is present
–  HCO3- (bicarb)
•  Secretion:
–  K+ secretion varies in
response to dietary intake
–  H+ secretion regulates pH
Loop of Henle & The Salty Medulla
CONCENTRATION OF URINE
10
Loop of Henle
Salty Medulla allows for Concentration of Urine
•  Osmolarity of blood refers to the
concentration of dissolved
substances, such as proteins, amino
acids, glucose, and ions in a liter of
plasma.
1.  Thin Descending limb is
passively permeable to H2O
•
As H2O leaves, filtrate
increases in osmolarity
2.  Thin Ascending limb is
passively permeable to
SOLUTE
•  Normal osmolarity of blood plasma
is about 300 mOsm/L
•
•  As a result of the function of the
Loops of Henle, interstitial fluid in
the medulla becomes progressively
hyperosmotic (1200mOsm/L)
towards the papilla
Na,Cl diffuses out through
leak channels
3.  Thick Ascending limb
Actively pumps out 1Na+ &
2Cl- against its
concentration gradient,
–  leaves very low osmolarity
filtrate (100mOsm) to enter
the DCT
•  *This osmotic gradient allows for
concentration of urine
Countercurrent
multiplier
•
•
Filtrate in Loop of Henle & blood in
Vasa Recta flow in opposite
directions.
Ascending limb actively pumps Na,
Cl out of filtrate and into blood.
•
The vasa recta carry the NaCl down
towards the papilla, picking up more
NaCl as it travels down, and creating
a hyperosmolar region (1200mOsm).
•
When blood in vasa recta travels up,
towards the cortex, it passes next to
the descending loop of henle, and
picks up water.
The blood returns to 300mOsm &
the water from the descending limb
is removed so it doesn’t “wash out”
the salty gradient.
•
ADH, ANP, RAA, PTH
HORMONAL REGULATION OF
SECRETION &
REABSORPTION
11
Hormonal Regulation of
Reabsorption & Secretion
Collecting Duct: ADH & Urine Concentration
5 Hormones affect reabsorption and
secretion:
1.
2.
3.
4.
5.
Antidiuretic Hormone (ADH) = Vasopressin
Angiotensin II
Aldosterone
Atrial Natriuretic Peptide (ANP)
Parathyroid Hormone (PTH)
ADH,aquaporins
•  The collecting duct is normally impermeable to water. Urine would
always be dilute if not for the presence of ADH (Anti Diuretic Hormone)
•  Only in the presence of ADH, can water leave the collecting duct
(facultative water reabsorption) following its concentration gradient
•  Filtrate becomes more concentrated
ADH Water Retention
•  ADH is secreted when blood
osmolality is high.(>300mOsm)
•  ADH causes Thirst & Water
Retention to correct the
elevated solute levels.
•  Since less water leaves in urine,
the Urine is more concentrated
•  Increased plasma osmolarity (or decreased blood volume) eg from
hemorrhage or severe dehydration stimulates osmoreceptors in hypothal.
•  Posterior pituitary releases ADH from brain into blood
•  ADH stimulates thirst & insertion of water channel proteins, aquaporin-2
into apical (luminal) side of principal cells.
•  Water can now leave lumen of collecting duct through aquaporins & diffuse
out basolateral side to enter blood capillaries, raising blood volume
•  Water that was reabsorbed into
the blood, raises Blood Volume
and decreases blood
osmolality
12
Angiotensin II: Retain NaCl & H2O. Vasoconstrict
Renin - Angiotensin - Aldosterone: RENIN
•  Juxtaglomerular
(Granular) Cells secrete
renin enzyme into blood
•  Triggers for renin release
1.  Low BP or Low blood
volume detected by
afferent arteriole
2.  Low NaCl- detected by
Macula densa or
3.  Sympathetic stimulation
•  Renin cleaves
angiotensinogen into
Angiotensin I
1.
2.
Aldosterone:
make more
Na/K Channels
•
•
•
•
ADRENAL CORTEX secretes Aldosterone in response to Angiotensin
Increases production of Na-K-ATPase pumps & Na, K, channel proteins
Results in Increased Na+ pumped into blood & K+ secretion into urine
Water follows NaCl, and is reabsorbed increasing blood volume
Increases TUBULAR NaCl reabsorption, and thus water reabsorption,
increasing blood volume & raising Blood Pressure. Powerful vasoconstrict
Stimulates Aldosterone release (affects collecting duct).
(ANP) Atrial
Natriuretic
Peptide:
Pee salt
•  Produced by atria of heart when blood
volume is increased
•  Causes natriuresis or excretion of Na+
•  Water follows sodium & Increases urine
output
•  Thus decreases blood volume.
13
Parathyroid Hormone (PTH) & Vit D
Kidney Activates
Vitamin D
Hormone
•  When blood Ca+ is low parathyroid glands make PTH
•  Stimulates early DCT to reabsorb more Ca2+
•  Vitamin D & PTH work together to increase blood calcium
Diuretics increase urine output
•  Diuretics are substances prescribed to treat hypertension because they
KIDNEY FUNCTION TESTS
–  decrease reabsorption of water
–  thus causing diuresis, an elevated urine excretion
–  which reduces blood volume
•  Some naturally occuring diuretics include
–  Caffeine- inhibits Na+ reabsorption; alcohol- inhibits secretion of ADH
14
Kidney Function is evaluated by:
•  Urine tests
–  24-hr Urine: Quantity of urine
–  Urinalysis: Quality of urine
•  Blood tests
–  blood urea nitrogen (BUN) (high is bad)
–  plasma creatinine (high is bad)
•  Renal plasma clearance tests
Dipstick urinalysis
Characteristics Of Normal Urine
•  Volume: 1-2 liters / 24hr
•  Color: yellow or amber
–  Concentrated urine is darker
–  Diet -reddish color from
beets medications, and
diseases may affect color
–  Kidney stones can produce
darker urine due to blood
•  Turbidity: transparent when
freshly voided
–  but becomes turbid (cloudy)
upon standing
•  Odor: mildly aromatic
–  becomes ammonia-like upon
standing
–  Diabetic urine has a fruity odor
due to ketone bodies.
•  pH: 4.6 - 8.0 (average 6.0)
–  High protein diets increases
acidity
–  vegetarian diets increase
alkalinity
•  Specific gravity (density): 1.001
- 1.035
–  Greater concentration of
solutes yields greater specific
gravity
BLOOD Urea Nitrogen (BUN)
•  Urea is a waste product
formed in the liver from
breakdown of dietary &
body proteins
•  Urea helps concentrate
urine in the renal
medulla
•  W/ low GFR (renal
disease / obstruction),
more urea is
reabsorbed into blood
& BUN rises.
•  Decreasing protein
intake decreases urea
production
15
Plasma Creatinine
•  Creatine is made in liver, stored
in muscle where it’s used for
phosphate storage
•  2% of creatine in muscle
degrades to creatinine
(waste)
•  Creatinine enters blood at
constant rate because muscle
mass is constant
•  100% of creatinine entering
kidneys is eliminated b/c its
small & not reabsobed
•  if your kidneys aren't
functioning properly,
creatinine may accumulate in
your BLOOD. High blood
creatinine (>1.5 mg/dL) = poor
renal function
•  Decreased blood creatinine
indicates decreased muscle
mass (i.e. muscular dystrophy)
Renal Plasma Clearance
•  How completely kidneys remove a given substance
from blood plasma in mL/min.
–  High renal plasma clearance = efficient excretion of a
substance in urine
–  low clearance = inefficient excretion of a substance
•  Examples:
–  Glucose clearance = 0. It’s all reabsorbed.
–  Penicillin’s clearance is high, requiring high dosage to
maintain adequate therapeutic value
–  Creatinine clearance - creatinine is filtered but not
reabsorbed or secreted. Thus creatinine clearance = GFR
Dialysis
•  With severe renal disease or
injury, blood must be
cleansed artificially by
dialysis.
•  Dialysis is the separation of
large solutes from smaller
ones through the use of a
selectively permeable
membrane.
•  After passing though the
dialysis tubing, the cleansed
blood flows back into the
patient’s body
URINE – STORAGE,
TRANSPORT & URINATION
16
Urine Transportation,
Storage, &
Elimination
•  Transportation:
–
–
–
–
–
–
collecting ducts
papillary ducts
minor calyces
major calyces
renal pelvis
ureters
•  Storage
–  urinary bladder
•  Elimination
–  urethra
Ureters
•  Peristaltic contractions of
the muscular walls of the
ureters push urine
towards the bladder
•  No anatomical valve
exists between the
ureters and bladder
•  Pressure from filling
bladder compresses
ureter openings
•  Prevents backflow of
urine and microbes
Urethra
Urinary Bladder
•  Hollow, distensible, muscular
organ posterior to pubic
symphysis. The muscularis,
also called the detrusor
muscle, is smooth muscle
•  When bladder is empty, it is
collapsed. When it is full, it
becomes spherical in shape.
•  internal urethral sphincter is
involuntary smooth muscle
•  external urethral sphincter is
voluntary skeletal muscle
•  Small tube from internal urethral orifice in floor of
the urinary bladder to the exterior of the body
•  In males, discharges semen from the body as well
as urine.
17
Micturition=
Urination
Urinary Incontinence
•  A lack of voluntary control over micturition is called urinary incontinence.
•  Micturition (urination, voiding) is discharge of urine from the urinary bladder
•  Bladder capacity is 700-800mL but Micturition reflex occurs when the
volume within the bladder exceeds 200 – 400 mL
•  stretch of the bladder wall sends signals to the micturation center at S2-S3.
•  Stress incontinence – physical stresses that increase abdominal
pressure, coughing, sneezing, laughing, exercising, pregnancy, walking
can cause leakage of urine from the bladder.
•  Those who smoke have twice the risk or developing urinary incontinence.
Su Wen Ch 6
The northern quadrant gives rise to the cold,
cold gives rise to water,
water gives rise to the salty taste,
the salty taste gives rise to the kidneys
the kidneys give rise to bones & marrow,
the marrow gives rise to the liver,
the kidneys master the ear.
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