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URINARY SYSTEM
Functions
• Excretion
– removal of organic wastes from body fluids
• Creatinine-by-product of muscle metabolism
• Nitrogenous wastes-urea from protein break down
• Elimination
– discharge of wastes from body
– micturition
• Homeostasis
– help regulate
• blood volume-has effects on blood pressure
• osmolarity-by integrating kidney function with behavioral
drives such as thirst
• ion balance-Na, K & Cl
• pH
• Detoxification
– excrete foreign substances found in blood
– drugs and toxins
Urinary System
• Kidneys
–
–
–
–
bean-shaped organs
either side of backbone
retroperitoneal area
between dorsal body wall &
parietal peritoneum
– Hilum
– area for entrance of blood
vessels, nerves, etc.
• excretory functions
•
– produce urine
Ureters
• hollow tube
• peristalsis moves urine to
bladder
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Bladder
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urine storage
capable of expanding
transitional epithelium
Urethra
–
carries urine to outside
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Kidney Structure
Renal Cortex
– outer
– light colored
Renal Medulla
– deeper
– made of 6-18 cone shaped tissue
masses-renal pyramids
base of each faces cortex
striped appearance
– collecting tubules
Renal columns
– inward extensions of cortical tissue
– separates pyramids
tip of each pyramid-renal papilla
– projects into renal sinus
ducts in renal papilla discharge urine into
minor calyx
8-18 minor calycesmergemajor calyx
2-3 major calices renal
pelvisureterbladder
Blood Supply
• served by renal artery
• enters hilus segmental
arteries  interlobar a.
arcuate a. interlobular
aretery  feeds renal lobes
• branch of interlobular a.
afferent arteriole
glomerulus
• departs by efferent
arteriole drains into
peritubular capillaries
surrounding nephron
interlobular veinarcuate v
interlobar v renal vein
Nephron
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basic structural & functional unit
– comprise bulk of kidneys
1 X 106 per kidney
urine production begins
85%-in cortex
– cortical nephrons
others begin in cortex & dip into
medulla
– juxtamedullary nephrons
consists of renal tubule + renal
corpuscle
renal tubule
long tube beginning at renal
corpuscle
renal corpuscle
consists of capillary networkglomerulus & a two layered
Bowman's or glomerular capsule
Renal Tubules
• proximal convoluted
tubule
– leaves glomerular capsule
– remains in cortex
• loop of henle
– hairpin loop
– descending & ascending
limbs
– extends into medulla
• distal convoluted tubule
– forms end of
tubule
– leads into collecting
duct
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Renal Corpuscle
things leaving plasma pass through renal
corpuscle
Bowman’s capsule + glomerulus
Bowman’s capsule
– outer, parietal layer
• made of simple squamous
epithelieum
– inner visceral layer
• made of podocytes
Podocytes wrap around capillaries of
glomerulus
forms filtration membrane
– comprised of glomerular capillary
visceral endothelium, basal lamina &
simple squamous parietal epithelium of
Bowman’s capsule
capsular space separates parietal & visceral
epithelia
glomerular capillaries are fenestrated
– pores-large allowing most blood
components to filter out of plasma but
small enough so RBCs cannot escape.
podocytes terminate in foot like processes
called pedicels that intertwine forming
openings-filtration slits
Juxtaglomerular Apparatus-JGA
• group of epithelial cells of
DCT near renal corpuscle
• taller than cells located
elsewhere along duct
• nuclei are clustered
together forming macula
densa
– lies adjacent to
juxtaglomerular cells (JC)
• Macula densa + JC cells
= JGA
• secretes renin &
erythropoietin
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Renal Physiology
goal of kidneys is to maintain homeostasis
does so by regulating blood volume & blood composition
involves excretion of solutes
Urea
– produced by amino acid breakdown
• Creatinine
– generated by skeletal muscle breakdown of creatinine PO4
• uric acid
– formed by recycling nitrogenous wastes from RNA
• solutes are dissolved in blood
– only eliminated dissolved in urine
• therefore to remove them kidney must also remove
water
• kidneys concentrate urine to prevent excess fluid loss
Urine Formation
• result of 3
processes
• Filtration
• Reabsorption
• Secretion
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Filtration
blood pressure forces water &
dissolved solutes out of capillaries into
capsular space
function of glomerulus
– only occurs at renal corpuscle
solutes removed from plasma by size
as fluid moves from blood into lumen
of nephron-passive
bad & good things are filtered out
creates filtrate
liquid almost identical to plasma in
composition-glomerular filtrate
– similar to plasma but without
proteins
– two are nearly isoosmotic
180 L of plasma move into nephrons
each day
destined for removal
Tubular Reabsorption
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removal of waste & solute from filtrate
from lumen of nephron into peritubular
capillaries & back into blood
job of renal tubules
primary function of proximal tubules
material not reabsorbed passes from
proximal tubule into Loop of Henle
– primary site for creation of dilute
fluids
filtrate passes through loop
– more solute is reabsorbed than water
– producing hypoosmostic fluid
by time filtrate leaves loopaverage
osmolarity is 100mOsm
volume has been reduced to 18L
from loop of Henle filtrate passes into
distal tubule &collecting ducts
– fine regulation of Na & water balance
– hormonally controlled
Tubular
Secretion
• movement of fluid
from blood into
tubular fluid
• selective
• takes place along
length of renal
tubules
• backs up filtration
– filtration does not
force all dissolved
materials out of
plasma
Glomerular Filtration
• passive, non-selective
• fluids & solutes are forced
through filtration membrane
by hydrostatic pressure
• filtration membrane is
simple
• mechanical filter
• requires no metabolic
energy
• water & small molecules are
filtered out by size
• determined by fenestrations
& slits of filtration
membrane
Glomerular Filtration
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primary pressures involved
GBHP-glomerular blood
hydrostatic pressure
– result of blood pressure in
glomerular capillaries
– higher here than elsewhere
– about 55 mm Hg
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because afferent arteriole is much
larger than efferent arteriole
change in diameter creates
resistance & therefore higher
pressure is needed to force blood
into efferent arteriole
pressure pushes water & solutes
out of plasma into filtrate
GBHP-opposed by capsular
hydrostatic pressure-CHP
– about 15mm Hg
•
capsular hydrostatic pressure
tends to push water & solutes out
of filtrate into plasma
Glomerular Filtration
• BCOP-blood colloid
osmotic pressure
• pressure due to
proteins in blood
• 30mm Hg
• NFP-net filtration
pressure equals
• GBHP – CHP – BCOP
• 55 mm Hg -15mm Hg 30mm Hg = 10 mm Hg
• favors filtration
Glomerular Filtration Rate-GFR
• amount of filtrate formed/minute
• normal-125ml/min for males &
105ml/min for females
• homeostasis of body fluids
requires that kidneys maintain
relatively constant GFR
• if too high substances pass so
quickly that some are not
reabsorbed & are lost in urine
• if too low, nearly all filtrate may
be reabsorbed & certain wastes
may not be eliminated & ph
control may be jeopardized
Glomerular Filtration Rate-GFR
• GFR is related to pressures that
determine filtration pressure
• any change in NFP will affect
GFR
• NFP is determined by renal
blood flow & blood pressure
• changes in either will affect GFR
• severe blood loss reduces MAP
(mean arterial pressure) &
decreases glomerular blood
hydrostatic pressure
• filtration ceases if GBHP drops to
45mm Hg because opposing
pressures add up to 45mm Hg
• when systemic blood pressure
rises above normal NFP, GFR
increases very little
• GFR is nearly constant when
blood pressure is 80 – 180mm
HG
Controlling GFR
• regulatory mechanisms ensure GFR is kept within
normal limits
• mechanisms that regulate GFR
– adjust blood pressure into & out of the glomerulus
– alter glomerular capillary surface area available for
filtration
• GFR increases when blood flow into glomerulus
increases
• 3 mechanism control GFR
• renal autoregulation
• nervous regulation
• hormonal mechanisms
Renal Autoregulation
• ability of nephrons to adjust
own blood flow & GFR
• two mechanisms
• myogenic mechanisms
• tubuloglomerular feedback
Myogenic Mechanisms
• works by changing diameter of afferent arteriole
• based on tendency of smooth muscle to contract when
stretched
• increase in blood pressure increases GFR because renal
blood flow increases
• blood pressure increasessmooth muscles in afferent
arteriole’s wall stretchesmuscle cells contract
narrows lumen of arteriole
(vasoconstriction)increases resistance to flow
blood flow to glomerulus decreasesreduces GFR to
previous level
• blood pressure decreasessmooth muscle cells
stretched lessafferent arteriole dilatesrenal blood
flow increasesGRF increases
• normalizes blood flow & GFR within seconds
Tubuloglomerular Feedback
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GFR-above normal due to elevated
blood pressure fluid flow increases
along tubules
PCT & loops of Henle have less time
to absorb Na, Cl & water
macula densa cells detect this
release a paracrine
paracrine causes constriction of
afferent arteriolereduces GFR
when blood pressure decreases &
GRF decreases macula densa
cells secrete another paracrine
afferent arterioles dilate (relax)
blood flow increases GFR
increases
Neural Regulation of GFR
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autoregulation cannot compensate for extreme
blood pressure changes
sympathetic nerve fibers supply efferent &
afferent arterioles
blood pressure risesrelease
norepinephrinebinds to alpha one receptors in
afferent arteriolesvasoconstriction  inhibits
filtrate formation decreases GFR
at rest sympathetic innervations is moderately
lowafferent & efferent arterioles are
dilatedrenal autoregulation controls GFR
moderate sympathetic stimulationafferent &
efferent arterioles contract to same degree
blood flow into & out of glomerulus is restricted
to same extentdecreases GFR only slightly
greater stimulation of sympathetic nerves
(exercise, hemmorage)afferent arteriole
constrictsblood flow & GFR decreased
lowering renal blood flow has two
consequences: reduces urine output which
helps to conserve blood volume
permits greater flow of blood to other tissues
Hormonal Control
• 2 hormones important to GRF
regulation
• Angiotensin II-reduces GFR
• vasoconstrictor
• causes constriction of both
afferent & efferent arterioles
reduces renal blood flow &
decreases GFR
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ANP (atrial natriuretic peptide) made
in atria of heart
increases GFR
blood volume increasesatria
stretchANP secretedrelaxes
glomerular mesangial
cellsincreases surface area
available for filtrationGFR
increases as surface area increases
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Renal Tubules
Proximal convoluted tubule
– absorbs organic nutrients, ions &
water
Loop of Henle
– descending limb
– ascending limb
peritubular capillaries connect limbs to
vasa recta
– long straight capillaries in medulla
running parallel to loop of Henle
distal convoluted tubule (DCT)
– initial part passes between
afferent & efferent arterioles
secrete solutes into filtrate
reabsorbs Na, Ca &water
opens into collecting ducts
receives filtrate from many
nephronspapillary ductminor
calyx
Reabsorpton
• recovers useful materials that enter
filtrate
• organic nutrients
– facilitated transport & cotransport
– 90% of glucose, amino acids &
other organic nutrients
reabsorbed by PCT
– PCT actively transports Na, K,
Mg, HCO3, PO4 & SO4
– 90% of bicarbonate is
reabsorbed by PCT
– 65% water is reabsorbed by
osmosis at PCT
• passively reabsorbs urea, Cl & lipid
soluble materials
• ascending limb reabsorbs Na, K &
Cl
• DCT reabsorbs Na, Cl, HCO3, water
• Collecting duct reabsorbs water and
urea
Reabsorpton Methods
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Diffusion
Osmosis
Carrier mediated transport
facilitated diffusion
– uses carrier protein transports
without spending energy
• active transport
– uses ATP
– includes pumps & carrier
proteins
• cotransport
– 2 substrates cross membrane
bound to one carrier protein
• counter (anti) transport
– 2 transported substances move
in opposite directions
Transport Maximum
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transport proteins are limited
there is a limit to amount of solute that
can be reabsorbed
all transport proteins are full
saturation point
– transporters are saturated some
solute will appear in urine
– maximum rate of transport is reached
– transport maximum Tm
Tm determines renal threshold
– plasma concentration at which
specific compound appears in urine
renal thresholds vary with substance
– glucose-180mg/dL
normal plasma glucose concentrations- all
glucose entering nephron is reabsorbed
before reaches end of proximal tubule
tubule epithelium has enough carriers to
capture glucose as flows past
glucose concentrations too highcarriers
saturatedglucose in urine
Tubular Secretion
• transports materials from
blood into glomerular
filtrate
• in PCT & nephron loop
secretion serves to
remove waste-urea, uric
acid, bile acids, ammonia,
catecholamines,
prostaglandins & creatine
• tubule secretion of
hydrogen & bicarbonate
ions help regulate pH
levels
Nephron Loop & Urine Formation
• limbs have different
permeability
• descending limb
– permeable to water
– impermeable to solutes
• ascending limb
– impermeable to water &
solutes
– has active transport
mechanisms to pump Na, Cl
& K from tubular fluid into
extracellular fluid
Nephron Loop & Urine
Formation-Countercurrent Multipliation
Mechanisms
• recaptures salt, returning
it to medullary tissue
• Multitplier-multiplies
salinity of medulla
• Countercurrent-fluid flows
in opposite directions in
the two limbs
• establishes
concentration gradient
allowing passive
reabsorption of water from
tubular fluid into collecting
system
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Consequences of Permeability
Differences
descending limb
– permeable to water
– impermeable to solutes
water passes by osmosis from tubule
into extracellular fluid leaving salt
behind
tubule contents continue to increase in
osmolarity reaching about 1200
mOsm/L by time fluid reaches bend at
end of loop
keeps osmolarity of medulla high
ascending limb
– impermeable to water & solutes
– has active transport mechanisms
to pump Na, Cl & K from tubular
fluid into extracellular fluid
water remains in tubule making tubular
fluid more and more dilute as nears
cortex
about 100 mOsm/L by time reaches
top of loop
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Counter Current Multiplication
Review
Na & Cl pumped out of ascending limb into ECF
– elevates osmotic concentration in extracellular fluid
(ECF) around descending limb resulting in osmotic
flow of water out of descending limb ECF
descending limb is permeable to water but not to solutes
removal of water increases solute concentration in
descending limb
fluid becomes hypertonic
arrival of highly concentrated solution in ascending
limb (osmolarity of filtrate peaks at elbow of loop at
1200mOsm) accelerates transport of Na & Cl into ECF of
medulla
osmolarity of medulla increases along descending limb
no osmosis can occur at ascending limb because is not
permeable to water
as Na & Cl are removed solute concentration in tubular
fluid decreases becoming hypotonic
– positive feedback arrangement
key to making concentrated urine is high osmolarity of
medulla
– without this there would be no concentration
gradient & as result no osmotic movement of water.
loss of Na & Cl from lumen causes osmolarity of tubule
fluid to decrease from 1200 to 100 mOSM at cortex
net result
high solute concentration generated & maintained in
medulla while tubule fluid becomes hypotonic
Countercurrent Exchange-Vasa
Recta
• blood vessels surrounding
nephron-vasa recta
• water & solutes which move
into surrounding tissue are
removed by vasa recta
– freely permeable to water
& salt
• return water to blood
• maintain high osmolarity of
medulla
Hormonal Control of
without hormones, distal
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Reabsorption
tubules & collecting
ducts are relatively
impermeable to water
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Angiotensin II Control of
Reabsorption
blood volume or blood pressure decrease
walls of afferent arterioles stretched
lessJG cells renin
converts angiotensinogenangiotensin I
angiotensin converting enzyme, ACE, in
lungs, proximal tubules & other tissues,
converts angiotensin I to angiotensin II
angiotensin II vasoconstricts afferent
arteriolesincreases blood pressure
increases GFR
stimulates NaCl & water reabsorption at
proximal convoluted tubule
stimulates adrenal cortex to secrete
aldosterone
promotes sodium & water retention by
distal convoluted tubule & collecting duct
Angiotension II further stimulates
secrection of ADH by pituitary water
reaborption increases & stimulates thirst to
encourage behavioral changes in water
consumption
all together these raise blood pressure by
reducing water loss, encouraging water
intake & constricting blood vessels
Aldosterone
• reninadrenal
cortex aldosterone
 water & Na
retention
increases blood
volume & blood
pressure
• aldosterone
stimulates principle
cells in collecting
ducts to absorb Na
and Cl & to secrete
more K ions
ADH
• ADH or vasopressin released
from posterior pituitary
regulates facultative
reabsorption of water by
increasing water permeability
of principle cells in late part of
DCT & collecting ducts
• Na & water reabsorption are
separately regulated in distal
nephron
• Facultative-reabsorption of
water not coupled to other
solutes
• Obligatory-reabsorption of
water that is coupled to other
solutes-where sodium goes
water follows
ADH
• within principle cells are tiny
vesicles containing many copies of
water channel proteins-Aquaporin2
• ADH stimulates insertion of these
into apical membrane of cells in
DCT & collecting ductsincreases
water permeability
• controlled by negative feedback
mechanism
• osmolarity or osmotic pressure of
plasma is increased (ie. when water
concentration is low)
osmoreceptors in hypothalamus
detect changesends impulses to
posterior pituitaryADHprinciple
cells more permeable to
waterwater reabsorption
increasesplasma osmolarity
returns to normalosmoreceptors
noticestop ADH release
ANP
• made by atria of heart
• inhibits reabsorption of
Na & water in PCT and
collecting duct
• also suppresses
secretion of ADH &
aldosterone
• these increase excretion
of Na in urine
• increases urine output
which decreases blood
volume & blood pressure
Parathyroid Hormone
• released from
parathyroid gland
in response to low
levels of blood
calcium
• increases Ca
reabsorption by
early DCT
Evaluation of Kidney Function
• several ways to determine how effectively kidneys are
functioning
• most used & easiest-urinalysis
• urine is evaluated for volume, physical & chemical
properties
• renal clearance
– way to access functions & to access renal function
indirectly
– volume of blood cleaned or cleared of a substance per
unit time (ml/min)
– assesses renal function by using urine &blood values
• Renal Clearance = S = U X V/P U=concentration of
substance in urine, P=concentration of substance in
plasma and V= urine flow in ml/minute
Renal Clearance
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Renal clearance (C) = UV/P
U = urea concentration in urine
V = rate of urine output
P = urea concentration in plasma
U = 6.0 mg/ml, V = 2ml/min and P = 0.2 mg/ml
then C = 60ml/min
means 60ml of blood is completely cleared of
urea each minute
estimates GFR
cannot be exactly determined by urea excretion
some urea is secreted into renal tubule and not
filtered by glomerulus
some urea that is filtered by glomerulus not
reabsorbed
Renal Clearance
• depends on 3 basic processes: filtration, secretion &
reabsorption
• for a substance that is filter but not reabsorbed or secreted
clearance = GFR
• all the molecules that pass filtration membrane appear in
urine
• GFR can be obtained with inulin
– polysaccharide from dahlia plant
– not normally found in body
– neither reabsorbed or secreted
• rate at which it appears in urine can be used to calculate
GFR
• all inulin will be filtered & end up in urine
• for inulin GFR = Renal Clearance = 125ml/min
Creatinine Clearance Test
• can be used to estimate GFR
• compares blood & urine creatinine concentrations
• creatinine-breakdown product of phosphocreatine
– energy storage compound in muscle
• produced & removed at constant rate from blood
• filtered & not reabsorbed in significant amounts (15%)
• only 2 ways for substance to be in urine
• filtered at glomerulus or secreted from peritubular capillaries into
tubules
• GFR = amount of substance eliminated divided by amount of
substance in plasma
• Kidneys eliminate 84mg of creatinine/hour & plasma creatinine =
1.4mg/dL
• 84/1.4 = 60dL/hr = 100ml/min
• because nearly all creatinine appears in urinechange in rate of
creatinine excretion may reflect renal disorder
• Filtration
Excretion
– occurs as blood flows through
glomerulus
– removes materials from blood
• Reabsorption
– materials & fluids are taken back
into the blood
• Secretion
– along nephron tubular system
– substances not cleared by
filtration are placed into filtrate
– resulting fluid called urine bears
little resemblance to filtrate made
at Bowman’s capsule
• glucose, amino acids, useful
metabolites have been
reabsorbed
• organic wastes have become
more concentrated
Ureters
• from collecting
ducts, urine enters
renal
pelvisureter
• lined with
transitional
epithelium
The Bladder
• from ureterbladder
– urine is stored
– released in process termed
micturition
• hollow muscular sac
• lined with transitional
epithelium
• can hold 700 – 800 ml
• neck-continuous with urethra
• opening closed by 2 muscle
rings or sphincters
• Internal
– smooth muscle
• External
– skeletal muscle
• sphincters operate by simple
spinal reflex
Micturition
• bladder fills (200-400mls)walls
stretchstretch receptors
sensory neurons spinal
cordmicturition center in sacral
spinal cordparasympathetic
smooth muscle in bladder wall &
internal sphinctercontraction of
detrusor muscles of bladder &
relaxation of internal sphincter
• for urination to completeexternal
sphincter must relax
• fibers from cerebrum inhibit
neurons supplying sphincter
– voluntary component of
urination process.
– ability to prevent reflex is
learned