Urinary System
Kidneys: formation of urine
-contains the functional unit for filtration =
Nephron
-production of urine, absorption of water
and salts
Ureters: transfer of urine from kidneys
to bladder
Urethra: transfer of urine from bladder to
outside
- longer into the male (20 cm vs. 4 cm in
the female)
Kidneys
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10-12 cm
retroperitoneal – behind the peritoneum
– not part of the abdominal cavity
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surrounded by three layers of tissue
– 1. deepest layer = renal capsule – transparent
sheet of dense irregular connective tissue
• continuous with the outer coat of the ureter
– 2. middle layer = adipose capsule
• amass of fatty tissue surrounding the renal
capsule
– 3. outer layer = renal fascia
• thin layer of dense irregular connective tissue that
anchors the kidney to the abdominal wall
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divided internally into an outer cortex and an
inner medulla
– medulla consists of 8 to 18 cone-shaped regions
called renal pyramids
– the wider base faces towards the cortex, the
narrow region (renal papilla) projects down
into a cup-like structure called a minor calyx
– renal cortex is divided into an outer cortical
zone and a deeper juxtamedullary zone
– the cortex also extends down in between the
pyramids to form the renal columns
– renal lobe = renal pyramid + the overlying
renal cortex + ½ the adjacent renal colum
Blood supply
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supplied by a renal artery and drained by a renal
vein(s)
kidney receives 20-25% of the resting cardiac output
through the renal arteries (1200mL per minute)
renal artery divides into segmental arteries –
supply segments of the kidney
the segmental arteries give off branches that pass
through the renal columns – interlobar arteries
at the base on the renal pyramids – between the
medulla and cortex – they are called arcuate
arteries
divisions from the arcuate are called the
interlobular arteries (pass between the renal lobes)
the afferent arterioles are derived from the
interlobular arteries
afferent arteriole supplies one nephron and forms
the glomerulus (capillary network)
drainage of the glomerulus is via the efferent
arteriole
efferent arteriole forms the peritubular capillary
network which surround the upper portions of the
nephron
an extension of this network covers the lower
portion of the nephron (loop of henle) – vasa recta
the peritubular capillaires form the interlobular veins
– arcuate veins – interlobar veins – renal vein
The Nephron
-about one million nephrons
-kidneys filter 180 L fluid per day!!!!
-each nephron is a renal corpuscle + renal tubules
-renal corpuscle: filtering unit consisting of a
tangled cluster of capillaries -> glomerulus +
Bowman’s capsule
-tubules: for reabsorption of water and ions leading
to final urine volume and composition
-PCT +Loop of Henle + DCT
Cortical Nephron
• 80-85% of nephrons are cortical nephrons
• Renal corpuscles are in outer cortex and loops of Henle lie
mainly in cortex
Juxtamedullary Nephron
• 15-20% of nephrons are juxtamedullary nephrons
• Renal corpuscles close to medulla and long loops of Henle extend into
deepest medulla enabling excretion of dilute or concentrated urine
Urinary System Function
1. Excretion of Metabolic Wastes: nitrogenous wastes
-Urea: by-product of amino acid metabolism
-produced when ammonia + carbon dioxide
-Creatinine: produced by breakdown of creatine phosphate
(high energy molecule reserve of muscles)
-Uric acid: by-product of nucleotide breakdown
-insoluble and ppts in the blood, concentrates in joints
2. Water-Salt balance of blood: reabsorption into blood from the descending
Loop of Henle, from collecting duct
-reclaim salt from the ascending portion of Loop of Henle
-reclaim urea from bottom section of collecting duct
-release of anti-diuretic hormone by pituitary: increase reabsorption of water
3. Acid-Base balance of blood: reabsorption of bicarbonate ions from urine in the
nephron decreases levels in blood (decreases carbonic acid levels)
-movement of hydrogen ions from blood into the nephron, combines
with ammonia to form ammonium (NH4+)
4. Secretion of hormones: release of renin by kidneys which leads
to release of aldosterone by adrenal glands (reabsorption of
salts by kidneys)
-release of erythropoietin by kidneys (stimulates RBC production)
-activation of vitamin D produced by the skin
Water Balance
-extracellular fluids: blood plasma, interstitial fluid, CSF, etc….
-intracellular fluids: cytosol
-unique distribution of ions in ECF and ICF
e.g. -intracellular fluids: higher potassium, phosphate, magnesium
- lower sodium, chloride and bicarb ions than in extracellular fluid
-of the 40 liters of water in the average male - 37% is ECF and 63%
is ICF
-so the kidney’s ability to modulate the composition of blood plasma
can determine the composition of interstitial fluid and therefore ICF
Water Intake
-average intake - 2.5 L
(60% from drinking water, 30% from moist foods, 10% byproduct
of metabolism)
-regulation of intake - thirst center within the hypothalamus
e.g. as body loses water - osmoreceptors within the thirst center
detect increase in osmotic pressure within the ECF
(increase as little as 1%)
-drinking distends the stomach which inhibits signalling from the
thirst center
Water output
-loses through urine, feces and sweat plus respiration and skin evaporatio
-2.5 L of water must be lost for water balance
-60% lost in urine, 6% in feces, 6% in sweat, 28% evaporation
from skin and lungs
-primary means of controlling output is through urine production
-dehydration: ECF becomes concentrated - increase osmotic pressure
- pressure increase detected by osmoreceptors in hypothalamus
-posterior pituitary gland releases anti-diuretic hormone (ADH)
-ADH causes distal convoluted tubule and collecting duct to
increase water reabsorption
-excess water intake: ECF less concentrated - decrease in O.P
-osmoreceptors signal to the post. pituitary
-P.P decreases ADH release
-kidney/nephrons decrease water reabsorption
Renal physiology
• comprised of filtration at the capsule (1)
• reabsorption through the tubules (2)
• direct secretion by the cells lining these tubules (3)
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glomerulus: capillary tangle derived from afferent arterioles (into) and lead into
efferent arterioles (out)
surrounded by a glomerular capsule (Bowman’s capsule) – single layer of epithelial
cells
glomerular capsule: site of initial filtration and the first step in the formation of urine
– consists of visceral and parietal layers
– visceral layer consists of modified epithelial cells = podocytes
– the podocytes wrap around the endothelial cells of the glomerular capillaries and forms the
filtration membrane together with the endothelial cell wall
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slits are covered with a slit membrane that permits the passage of small molecules such as water, vitamins, amino
acids, wastes and small plasma proteins
– space between the visceral and parietal layers = glomerular capsule
– between the union of the afferent and efferent arterioles are mesangial cells that help regulate
the rate of glomerular filtration
• 1. Glomerular filtration
Renal Physiology
– depends on three main pressures
• 1. glomerular blood pressure (GBP) – BP in the glomerular capillaries (55 mmHg)
– promotes filtration by forcing water and solutes through the filtration membrane
• 2. caspsular hydrostatic pressure (CHP) – hydrostatic pressure exerted against the filtration
membrane by fluid already in the bowman’s capsule
– opposes filtration from the blood
– 15 mm Hg
• 3. blood collioid osmotic pressure (BCOP) – due to the presence of plasma proteins in the
blood
– opposes filtration from the blood
– 30 mmHg
• net filtration pressure (NFP) = GBP – CHP – BCOP = 10 mm Hg
• loss of plasma proteins in the urine can cause edema (increased interstitial fluid)
– damage to the glomerular capillaries can increase their permeabilty – loss of the larger
plasma proteins
– this increases the BCOP which draws larger amounts of water out of the blood and into
the urine
– but the BCOP decreases because we are losing these plasma proteins in the urine
– the overall drop in BCOP causes water to leave the blood and enter the tissues
systemically
Glomerular filtration rate
• glomerular filtration rate (GFR) – amount of filtrate
formed per minute (125 mL/min)
– affected dramatically by NFP
– adjusted by regulating: 1) blood flow into and out of the
glomerulus and 2) the glomerular capillary surface area available
for reabsorption
– three mechanisms control GFR
GFR
• 1. renal autoregulation – two mechanisms – myogenic mechanism and
tubuloglomerular feedback
– myogenic mechanism – increased blood volume can increased GFR
• by the stretching of the afferent arterioles triggers the contraction of the smooth
muscle lining these arterioles
– tubulogomerular mechanism – feedback provided to the glomerulus from the
renal tubules
• increase in the fluid through the PCT, LH and DCT – less time to reabsorb
materials
• cells in these tubules induce vasoconstriction in the afferent arterioles
• if GFR drops below normal – these cells stimulate the release of NO from the
juxtaglomerular cells – vasodilation which increases blood flow and GFR
• 2. neural regulation – sympathetic ANS fibers release norepinephrine
which causes vasoconstriction of the smooth muscle in the afferent
arteriole
• 3. hormonal regulation
– release of angiotensin II reduces GFR by inducing vasoconstriction
– also release of atrial natriureic peptide (ANP – from the cardiac cells)
increases GFP by increasing the surface area of the glomerulus
PCT and Loop of Henle
• proximal convoluted tubule: first area of reabsorption into blood ->
Loop of Henle -> distal convoluted tubule -> collecting duct ->
union of ducts into ureter
• cells of these tubules are also single epithelial layers – vary as either
cuboidal (PCT and DCT, descending) or squamous (ascending LH)
• PCT and DCT surrounded by the peritubular network of capillaries for
reabsorption back into the blood, LH is covered with the vasa recta
• PCT is the site of water reabsorption (PASSIVE) - associated with the
ACTIVE reabsorption of sodium and potassium ions
– active Na+ and K+ uptake by the blood from the PCT is by sodium pumps
- sodium pumped from the PCT and chloride, bicarbonate and phosphate
ions follow it - salt reabsorption
– the active transport of ions into the blood plasma increases osmotic
pressure within the blood
– therefore water moves out of the PCT into the capillaries PASSIVELY!
• PCT reabsorbs about 70% of filtered Na+, ions and water
– the apical surface of the PCT epithelium forms microvilli which increases
the surface area of this region
Loop of Henle
• active transport of Na+ continues through the loop of Henle
and DCT
• descending loop of Henle is quite permeable to water but
impermeable to solute movement – urine becomes hypertonic
(increased ions within the urine, decreased water)
• ascending loop is the opposite – permeable to salt (salt pumped
out of the urine back
• into the blood plasma)
• the wall of the arterioles alongside the ascending portion of the
LH contain modified smooth muscle cells = juxtaglomerular
cells
– regulate blood pressure within the kidneys
DCT and Collecting Duct
• two types of cells found in the DCT and CD
– principal cells – receptors for ADH and aldosterone
– intercalated cells – play a role in the homeostasis of
blood pH
• DCT and collecting duct are impermeable to water
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• the DCT and CD become permeable upon action
of hormones
Renal Physiology
• Tubular reabsorption
– tubule cells reabsorb about 99% of the filtered water and many of the
solutes
– principal materials reabsorbed – glucose, aminao acids, urea, Na+, K+, Ca+,
Cl-, HCO3- and HPO4– return to the blood through reabsorption into the peritubular capillary
network and vasa recta
– reabsorption = return to the blood
– absorption = entrance of new materials into the blood (e.g. via digestive
absorption)
– reabsorption routes – one of two routes before re-entering the blood
Reabsorption Routes
• Paracellular reabsorption
• between adjacent tubule cells into the
blood
– 50% of reabsorbed material
moves between cells by
diffusion in some parts of
tubule
• Transcellular reabsorption
– material moves through
both the apical and basal
membranes of the tubule
cell by active transport
Renal Physiology
• Tubular secretion
– tubular cells also secrete other materials –
wastes, drugs, excess ions into the urine
– this also removes these materials from the
blood
Reabsorption in the PCT
Reabsorption of Nutrients
• Na+ symporters help
reabsorb materials from
the tubular filtrate
• Glucose, amino acids,
lactic acid, water-soluble
vitamins and other
nutrients are completely
reabsorbed in the first half
of the proximal convoluted
tubule
• Intracellular sodium levels
are kept low due to
Na+/K+ pump
Reabsorption of Bicarbonate, Na+ & H+ Ions
• Na+ antiporters reabsorb Na+
and secrete H+
– PCT cells produce the H+ &
release bicarbonate ion to the
peritubular capillaries
– important buffering system
• For every H+ secreted into the
tubular fluid, one filtered
bicarbonate eventually returns
to the blood
Passive Reabsorption in the 2nd Half of PCT
• Electrochemical gradients
produced by symporters &
antiporters causes passive
reabsorption of other
solutes
• Cl-, K+, Ca+2, Mg+2 and
urea passively diffuse into
the peritubular capillaries
• Promotes osmosis in PCT
(especially permeable due
to aquaporin-1 channels
Secretion of NH3 & NH4+ in PCT
• Ammonia (NH3) is a poisonous waste
product of protein deamination in the liver
– most is converted to urea which is less toxic
• Both ammonia & urea are filtered at the
glomerus & secreted in the PCT
– PCT cells deaminate glutamine in a process that
generates both NH3 and new bicarbonate ion.
• Bicarbonate diffuses into the bloodstream
– during acidosis more bicarbonate is generated
Reabsorption in the Loop of Henle
• Tubular fluid
– PCT has reabsorbed 65% of the filtered water
so chemical composition of tubular fluid in the
loop of Henle is quite different from plasma
– since many nutrients were reabsorbed as well,
osmolarity of tubular fluid is close to that of
blood
Countercurrent Mechanism:
Reabsorption at Loop of Henle
Symporters in the Loop of Henle
• Thick limb of loop of
Henle has Na+ K- Clsymporters that
reabsorb these ions
• K+ leaks through K+
channels back into the
tubular fluid leaving
the interstitial fluid
and blood with a
negative charge
• Cations passively
move to the vasa recta
Reabsorption in the DCT
• Removal of Na+ and Cl- continues in the
DCT by means of Na+ Cl- symporters
• Na+ and Cl- then reabsorbed into
peritubular capillaries
• DCT is major site where parathyroid
hormone stimulates reabsorption of Ca+2
– DCT is not very permeable to water so it is not
reabsorbed with little accompanying water
Reabsorption & Secretion in the
Collecting Duct
• By end of DCT, 95% of solutes & water
have been reabsorbed and returned to the
bloodstream
• Cells in the collecting duct make the final
adjustments
– principal cells reabsorb Na+ and secrete K+
– intercalated cells reabsorb K+ & bicarbonate
ions and secrete H+
Actions of the Principal Cells
• Na+ enters principal cells
through leakage channels
• Na+ pumps keep the
concentration of Na+ in
the cytosol low
• Cells secrete variable
amounts of K+, to adjust
for dietary changes in K+
intake
– down concentration gradient due to Na+/K+ pump
• Aldosterone increases this Na+ reabsorption (and passive water
reabsorption) & K+ secretion by principal cells by stimulating the
synthesis of new pumps and channels.
Secretion of H+ and Absorption of
Bicarbonate by Intercalated Cells
• Proton pumps (H+ATPases) secrete H+
into tubular fluid
– can secrete against a concentration gradient
so urine can be 1000 times more acidic than
blood
• Cl-/HCO3- antiporters move
bicarbonate ions into the blood
– intercalated cells help regulate pH of body
fluids
• Urine is buffered by HPO4 2- and
ammonia (secreted by cells of PCT),
both of which combine irreversibly
with H+ and are excreted
Production of Dilute or Concentrated Urine
• Homeostasis of body fluids despite variable fluid
intake
• Kidneys regulate water loss in urine
• ADH controls whether dilute or concentrated urine
is formed
– if lacking, urine contains high ratio of water to solutes
– dilute urine – reabsorption of ions is unchanged
(normal) but ADH decreases reabsorption of water
Summary
• H2O Reabsorption
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PCT---65%
loop---15%
DCT----10-15%
collecting duct--5-10% with ADH
Renin-Angiotensin-Aldosterone
• when blood volume and BP drop – the walls of the
afferent arterioles are stretched less –
juxtaglomerular cells secrete renin into the blood
(also stimulated by sympathetic stimulation)
• in the blood renin cleaves angiotensinogen (made
by hepatocytes) to form angiotensin I
• the enzyme ACE (in the lung) – cleaves this even
more to form angiotensin II
– 1. decreases GFR by causing vasoconstriction of
afferent arterioles
– 2. enhances reabsorption of Na+, Cl+ and water in the
PCT by stimulating the Na/H antiporter
– 3. stimulates the release of aldosterone by the adrenal
cortex – stimulates the principal cells of the DCT
collecting ducts to reabsorb more Na and Cl and secrete
more K into the blood
• osmotic consequence of this causes an increased reabsorption
of water
ADH and ANP
• ADH – released by the posterior pituitary
– regulated water reabsorption by increasing the permeability of the
principal cells in the DCT to water
– in the absence of ADH the principal cells of the DCT and CT have low
permeability to water
– within the principal cells are vesicles containing a protein called
aquaporin-2
• ADH stimulates the insertion of aquaporin-2 into the apical membrane
• water permeability increases
• when the OP of the blood plasma increases (decreased water concentration )
via increased filtration – osmoreceptors in the hypothalamus detect this drop
and stimulate the release of ADH
• increased permability to water reintroduces water back into the blood and
lower the OP of the blood plasma
• ANP – inhibits the reabsorption of Na and water in the PCT and the
collecting duct
– also suppresses the secretion of aldosterone and ADH
• increases the excretion of Na in the urine (natriuresis) and increase urine
output (diuresis) which decreases blood volume and BP and inhibits its further
release