BMS130

Physiological Sciences 2
School of Biomedical Sciences, Charles Sturt University

Topic: Urine formation I and II

Reference: Saladin, CH 23 pp 898-908
Lecturer: Drs James Wickham & Brian Spurrell

1 Images provided by Saladin, K. (2012). Anatomy & Physiology: the unity of formSchool
and function
of Biomedical Sciences
 Learning Objectives

1. Describe the filtration membrane and the process by which the

kidney filters the blood plasma
2. Explain the forces/factors that promote and oppose filtration
3. Describe how renal autoregulation controls glomerular filtration
rate
4. Describe how the nervous system controls glomerular filtration
rate
5. Describe how the renin-angiotensin-aldosterone mechanism acts
to control blood pressure
6. Describe tubular reabsorption and how it takes place
7. Describe tubular secretion and state solutes that are excreted
8. Describe how the nephron regulates water conservation

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 1. Describe the filtration membrane and the blood filtration process
Basic stages of urine formation
Blood flow
Conversion of glomerular filtrate
1 Glomerular filtration Renal to urine involves the removal
Creates a plasma like corpuscle
filtrate of the blood and addition of chemicals by
Flow of tubular reabsorption and
filtrate
2 Tubular reabsorption secretion
Removes useful solutes
from the filtrate, returns
Peritubular • Occurs through PCT to DCT
capillaries
them to the blood
• Tubular fluid is modified
3 Tubular secretion
Removes additional Basic stages of urine formation
wastes from the blood, include:
adds them to the filtrate Renal tubule
1. Glomerular filtration
4 Water conservation H2O
Removes water from the
H2O
2. Tubular reabsorption
urine and returns it to
blood; concentrates H2O 3. Tubular secretion
wastes
Saladin, Figure 23.9 4. Water conservation
Urine
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 1. Describe the filtration membrane and the blood filtration process
1: Glomerular filtration
• a special case of the capillary fluid
exchange process in which water
and some solutes in the blood
plasma pass from the capillaries of
the glomerulus into the capsular
space of the nephron
• Almost any molecule smaller than
Google images “blood filtration process”
3 nm can pass freely through the
filtration membrane
• Water, electrolytes, glucose,
fatty acids, amino acids,
nitrogenous wastes & vitamins
• 99% reabsorbed! = only 1-2 litres
of urine is formed/day Google images “filtration membrane of glomerulus”

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1. Describe the filtration membrane and the blood filtration process

Saladin, Figure 23.10

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 1. Describe the filtration membrane and the blood filtration process
The Filtration Membrane
• Filtration membrane—three
barriers through which fluid
passes
1. Fenestrated endothelium
of glomerular capillaries
• 70 to 90 nm filtration
Google images “glomerular basement membrane”
pores in capillaries
• Highly permeable type of
capillary
• Excludes larger molecules
like blood cells from
filtrate
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 1. Describe the filtration membrane and the blood filtration process

Filtration membrane

Capsular space
Podocyte

Foot processes
Filtration slits
Basement membrane

Filtration pore
Endothelial cell
Blood plasma

Erythrocyte
Saladin, Figure 23.10

0.5 mm

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 1. Describe the filtration membrane and the blood filtration process
The Filtration Membrane
2. Basement membrane
• Consists of a proteoglycan gel
• size alone excludes molecules > 8 nm
• Some smaller molecules also repelled
due to negative charge of membrane
(i.e. albumin; anion)
Google images
• Small protein bound solutes don’t pass “glomerular basement membrane”

3. Filtration slits of podocyte

• Podocyte cell extensions (pedicels)
wrap around the capillaries to form a
barrier layer with 30 nm filtration slits
• Also negatively charged which is an
additional obstacle for large anions Google images “podocyte”

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 2. Explain the forces/factors that promote and oppose filtration

Filtration Pressure
• Glomerular filtration rate (GFR), the
volume of filtrate formed per minute
(125 ml/min or 180ltrs/day for a male),
is governed by the same pressures that
determine filtration in the other blood
capillaries
• Glomerular hydrostatic pressure
(blood pressure) ~60mmHg
• Colloid osmotic pressure
(~32mmHg) opposes filtration
• Capsular hydrostatic pressure
(~18mmHg) exerted by fluids in
capsule
• Capsular colloidal osmotic pressure
~0mmHg
• Net Filtration Pressure
Saladin, Figure 23.12
= 60-32-18 = 10mmHg

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 2. Explain the forces/factors that promote and oppose filtration
Filtration Pressure
• Other factors promoting
filtration:
• Renal artery is one of the first
branches of abdominal aorta
and also a large branch hence
it receives a high volume of
blood flow
• Smaller diameter efferent
arteriole (exit point)
compared with afferent Google images “renal artery”
arteriole (entry point)
promotes higher pressures in
the glomeruli
• Also dependant on your blood
pressure, filter permeability
and surface area of the
filtration membrane

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3. Describe how renal autoregulation controls glomerular filtration rate

Regulating Glomerular Filtration Rate

• GFR - controlled by adjusting glomerular blood
pressure by multiple mechanisms:
• Renal Autoregulation
• Myogenic mechanism
• Tubuloglomerular feedback
• Sympathetic control
• Hormonal mechanisms
• Renin and Angiotensin

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3. Describe how renal autoregulation controls glomerular filtration rate

Renal Autoregulation of GFR

• The ability of the nephron’s to adjust their own
blood flow and GFR without external control

• Myogenic mechanism: based on the tendency of

smooth muscle to contract when stretched
• Aim: to regulate blood flow so urine production
remains relatively constant
• Increased blood pressure stretches the afferent
arterioles  vasoconstriction of afferent arteriole
• Decreased blood pressure in afferent arteriole 
vasodilation or relaxation of afferent arteriole
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3. Describe how renal autoregulation controls glomerular filtration rate

Renal Auto regulation of GFR

• Tubuloglomerular
feedback
• High GFRs = less
reabsorption of NaCl in
renal tubules
• Macula densa provides
feedback to glomerulus
when NaCl levels in renal
tubules (DCT) are high
• Macula densa cells signal
(paracrines) JG cells to
inhibit release of nitric
oxide (a potent
vasodilator)
• Leads to vasoconstriction
of afferent arteriole
Saladin, Figure 23.13

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3. Describe how renal autoregulation controls glomerular filtration rate
Negative Feedback Control of GFR

Saladin, Figure 23.14

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4. Describe how the nervous system controls glomerular filtration rate

Sympathetic Control of GFR

• Strenuous exercise, acute conditions (circulatory shock) or simply
“fight or flight” situations stimulate afferent arterioles to constrict
which leads to  GFR and urine production and hence redirecting
blood flow to heart, brain and skeletal muscles where blood is
more urgently needed

Google images “smooth muscle

contraction”

Google images “glomerulus”

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4. Describe how the nervous system controls glomerular filtration rate

Sympathetic Control of GFR

• Sympathetic
stimulation can
also initiate renin
release when BP
drops

Google images “renin

sympathetic nervous system”

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5. Describe renin-angiotensin-aldosterone mechanism in controlling BP

Hormonal Control of GFR: The Renin-

Angiotensin-Aldosterone Mechanism
• Renin secreted by juxtaglomerular cells if BP drops
dramatically
• Renin converts angiotensinogen, a blood protein, into
angiotensin I
• In the lungs angiotensin-converting enzyme (ACE)
converts angiotensin I to angiotensin II, the active
hormone
• Works in several ways to restore fluid volume and BP

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5. Describe renin-angiotensin-aldosterone mechanism in controlling BP

Hormonal Control
of GFR: the Renin-
Angiotensin-
Aldosterone
Mechanism

Saladin, Figure 23.15

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5. Describe renin-angiotensin-aldosterone mechanism in controlling BP
The Renin–Angiotensin–Aldosterone
Mechanism
• Angiotensin II
• Potent vasoconstrictor raising BP throughout body
• Constricts efferent arteriole raising GFR despite low BP
• Lowers BP in peritubular capillaries enhancing reabsorption of
NaCl and H2O

• Angiotensin II stimulates adrenal cortex to secrete

aldosterone promoting Na+ and H2O reabsorption in DCT
and collecting duct

• Stimulates posterior pituitary to secrete ADH which

promotes water reabsorption by collecting duct
• Stimulates thirst and H2O intake
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5. Describe renin-angiotensin-aldosterone mechanism in controlling BP

Effects of
angiotensin II

Saladin, Figure 23.15

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 Learning Objectives

1. Describe the filtration membrane and the process by

which the kidney filters the blood plasma
2. Explain the forces/factors that promote and oppose
filtration
3. Describe how renal autoregulation controls glomerular
filtration rate
4. Describe how the nervous system controls glomerular
filtration rate
5. Describe how the renin-angiotensin-aldosterone
mechanism acts to control blood pressure

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 6. Describe tubular reabsorption and how it takes place
2: Tubular Reabsorption
Blood flow
2. Tubular Reabsorption:
1 Glomerular filtration Renal
Creates a plasma like corpuscle • Reclaiming water and
filtrate of the blood
Flow of solutes from the filtrate
filtrate
2 Tubular reabsorption and returning them to
Removes useful solutes
from the filtrate, returns
Peritubular the blood
capillaries
them to the blood
3 Tubular secretion
Removes additional
wastes from the blood,
adds them to the filtrate Renal tubule
4 Water conservation H2O
Removes water from the
H2O
urine and returns it to
blood; concentrates H2O
wastes
Saladin, Figure 23.9
Urine
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 6. Describe tubular reabsorption and how it takes place

Proximal Convoluted Tubules (PCT)

• Reabsorbs 65% of GF to
peritubular capillaries
• Great length, prominent
microvilli and abundant
mitochondria for active
transport
• Reabsorbs greater variety
of chemicals than other
parts of nephron

Google images “proximal

convoluted tubule”

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 6. Describe tubular reabsorption and how it takes place

Proximal Convoluted Tubule (PCT)

• Multiple routes in which fluid and solutes are reabsorbed
through tubule wall to capillaries
•transcellular route - through epithelial cells of PCT
•paracellular route - between epithelial cells of PCT
•Tight junctions between the cells are quite ‘leaky’
•Water absorbed by osmosis & carries other solutes with it
(solvent drag)
• NaCl uses symporters and antiporters that pump it into and out of
PCT epithelium
• Glucose is co-transported into the epithelium with Na + via sodium-
glucose transporters, 100% reabsorption
• Water is reabsorbed via aquaporins (transcellular route) and also
via paracellular route (180 ltrs of filtrate becomes 1-2 ltrs of urine)
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 6. Describe tubular reabsorption and how it takes place

Peritubular Tissue Tubule epithelial cells Tubular fluid

capillary fluid

Sodium–glucose
Glucose transport protein
Na
ATP + (SGLT) (symport)
Na+ Glucose
Na+–K+ pump
K+ Na+ Na+–H+
ADP + Pi H+
antiport
K+ Cl–
Cl––anion antiport
Cl– Anions
K+–Cl– Aquaporin
H2
symport
Tight junction O
Solvent drag
Transcellular route Brush H2O, urea, uric acid,
Paracellular route border Na+, K+, Cl–, Mg2+, Ca 2+, Pi

Saladin, Figure 23.16

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 7. Describe tubular secretion and state solutes that are secreted
III: Tubular Secretion
Blood flow

1 Glomerular filtration Renal

Creates a plasma like corpuscle 3. Tubular Secretion:
filtrate of the blood
Flow of • Movement of molecules
filtrate
2 Tubular reabsorption
Removes useful solutes
from the capillary blood
Peritubular
from the filtrate, returns
capillaries into the filtrate
them to the blood
3 Tubular secretion
Removes additional
wastes from the blood,
adds them to the filtrate Renal tubule
4 Water conservation H2O
Removes water from the
H2O
urine and returns it to
blood; concentrates H2O
wastes
Saladin, Figure 23.9
Urine
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 7. Describe tubular secretion and state solutes that are secreted
Tubular Secretion of PCT and the Nephron
Loop
• Waste removal
• urea, creatinine, uric acid,
bile salts, ammonia,
catecholamines, many
drugs
• Acid-base balance
• An ↑ secretion of
hydrogen ions and ↑
reabsorption of
bicarbonate ions ↑ pH of
body fluids
• A ↓ secretion of H+ and
↓ reabsorption of HCO3-
↓ pH of body fluids
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 8. Describe how the nephron regulates water conservation
4: Water conservation
Blood flow
4. Water conservation:
1 Glomerular filtration Renal
Creates a plasma like corpuscle • Movement of water
filtrate of the blood
Flow of from collecting duct into
filtrate
2 Tubular reabsorption blood
Removes useful solutes
Peritubular
from the filtrate, returns
capillaries
them to the blood
3 Tubular secretion
Removes additional
wastes from the blood,
adds them to the filtrate Renal tubule
4 Water conservation H2O
Removes water from the
H2O
urine and returns it to
blood; concentrates H2O
wastes
Saladin, Figure 23.9
Urine
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 8. Describe how the nephron regulates water conservation

The Nephron Loop

• Primary function of nephron loop
• water conservation
• generates salinity gradient, allows CD to concentrate
urine
• also involved in electrolyte reabsorption
• 25% of Na+, K+ and Cl- remaining in filtrate
• K+ is secreted back into the tubular fluid via the Na+-K+
pump
• NaCl stays in the tissue fluid of the medulla
• 15% of water remaining in filtrate
• Only in the thin portion of the loop

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 8. Describe how the nephron regulates water conservation

Summary of Tubular
Reabsorption and
Secretion

Saladin, Figure 23.22

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 8. Describe how the nephron regulates water conservation

The Distal Convoluted Tubule

and Collecting Duct
• Fluid arriving in the DCT still contains about 20% of the water
and 7% of the salts from glomerular filtrate
• If this were all passed as urine, it would amount to 36 L/day

• DCT and collecting duct reabsorb variable amounts of water

salt and are regulated by several hormones
• Aldosterone, atrial natriuretic peptide, ADH, and parathyroid
hormone
• More on this in next lecture.

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 8. Describe how the nephron regulates water conservation
Water Reabsorption by the Collecting Duct
Saladin, Figure 23.19
• Collecting duct (CD) begins in
Tubular fluid the cortex where it receives
(300 mOsm/L) tubular fluid from several
nephrons
300
Cortex • As CD passes through the
medulla, water is reabsorbed
Osmolarity of tissue fluid (mOsm/L)

Medulla
(aquaporins) and the urine
600 H2O
becomes 4 x more concentrated
H2O
• Medullary portion of CD is more
Collecting
900
H2O duct permeable to water than to NaCl
• As urine passes through the
H2O
Nephron increasingly salty medulla, water
1,200 loop
H2O is reabsorbed by osmosis,
Urine (up to 1,200 mOsm/L) concentrating urine
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 Learning Objectives

6. Describe tubular reabsorption and how it takes

place

7. Describe tubular secretion and state solutes that

are excreted

8. Describe how the nephron regulates water

conservation

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