Download Urinary Physiology Urine Formation Urine Formation Glomerular

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Urine Formation
• Filtrate
– Blood plasma minus most proteins
Urinary Physiology
Urinary Section pages 9-17
• Urine
– <1% of total filtrate
– Contains metabolic wastes and unneeded
substances
Urine Formation
Afferent arteriole
Glomerular capillaries
Efferent arteriole
1. Glomerular filtration
2. Tubular reabsorption
Cortical
radiate
artery
Glomerular capsule
Returns components to blood
Rest of renal tubule
containing filtrate
Glucose, amino acids, water and salt
3. Tubular secretion
Reverse of reabsorption
Selective addition to urine
4. Water conservation
Peritubular
capillary
Three major
renal processes:
Glomerular filtration
Tubular reabsorption
Tubular secretion
To cortical radiate vein
Urine
Figure 25.10
Glomerular Filtration
Occurs at renal corpuscle
Passive process driven by hydrostatic pressure
Glomerulus is a very efficient filter
Permeable membrane
Water and small solutes pushed through filter
Large surface area
Higher blood pressure
Efferent
arteriole
Glomerular capsular space
Proximal
convoluted
tubule
Afferent
arteriole
Glomerular capillary
covered by podocytecontaining visceral
layer of glomerular
capsule
Cytoplasmic extensions
of podocytes
Filtration slits
Parietal layer
of glomerular
capsule
(a) Glomerular capillaries
and the visceral layer of
the glomerular capsule
Podocyte
cell body
Fenestrations
(pores)
Glomerular capillary
endothelium (podocyte
covering and basement
membrane removed)
Foot processes
of podocyte
Figure 25.9a
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Glomerular Filtration
Filtration membrane
• Capillary endothelium
• Basement membrane
• Foot processes of podocyte
of glomerular capsule
Capillary
• Filtration membrane
– 3 components
• Fenestrated capillary endothelium
• Basement membrane
• Podocytes
– Allows passage of water and small solutes
• Fenestrations prevent filtration of blood cells
• Negatively charged basement membrane repels large
anions
Plasma
Fenestration
(pore)
Filtration slits
Filtrate in
capsular
space
Filtration
slit
Slit
diaphragm
Foot processes
of podocyte
(c) Three parts of the filtration membrane
Glomerular Filtration
Podocyte
cell body
Foot
processes
• Net Filtration Pressure (NFP)
– Glomerular hydrostatic pressure (HPg)
– Capsular hydrostatic pressure (HPc)
– Blood osmotic pressure (OPg)
(b) Filtration slits between the podocyte foot processes
Glomerular Filtration
Afferent
arteriole
Glomerular
capsule
• Net Filtration Pressure (NFP)
– The pressure responsible for filtrate formation
NFP = HPg – (OPg + HPc)
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
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Net Filtration Pressure
Glomerular Filtration
• Glomerular Filtration Rate (GFR)
NFP = HPG – (OPG + HPC)
= 55 mm Hg – (30 mmHg + 15 mmHg)
= 10 mmHg
Glomerular Filtration
• Factors affecting GFR
– Kidney disease
• ↓ blood osmo>c pressure, ↑ capsular osmo>c
pressure
– Hemorrhage
• ↓ glomerular blood hydrostatic pressure
– Hypotension
• Glomerular blood hydrostatic pressure = capsule
hydrostatic and blood osmotic pressure = filtration
stops!
– 125 ml/min
1800 liters of blood through kidneys/day
= 1200 ml/min = about 180 liters filtrate/day
Glomerular Filtration
• GFR is tightly controlled by two types of
mechanisms
– Intrinsic control (renal autoregulation)
• Act locally within the kidney
– Extrinsic controls
• Nervous and endocrine mechanisms that maintain
blood pressure and affect kidneys
– Termed renal suppression
Intrinsic Control
• Goal = Maintain a nearly constant GFR when
MAP is in the range of 80–180 mm Hg
– Renal autoregulation
• Mechanisms that cause vasoconstriction of afferent
arterioles in response to increased BP
• Reduces glomerular flow to keep
GFR the same
Extrinsic Controls
• Sympathetic nervous system
– At rest
• Renal blood vessels are dilated
• Renal autoregulation mechanisms prevail
• GFR maintained
– Extreme stress
• Norepinephrine and epinephrine released
• Both cause constriction of afferent arterioles
– Inhibits filtration
– Shunts blood to other vital organs
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Tubular Reabsorption
•
•
•
•
•
125 ml/min of filtrate produced
Most of this fluid is reabsorbed
A selective transepithelial process
Includes active and passive process
Most occurs in PCT
Tubular Reabsorption
• Transcellular route
Luminal membranes of tubule cells
Cytosol of tubule cells
Basolateral membranes of tubule cells
Tubular Reabsorption
• PCT
– Site of most reabsorption
•
•
•
•
65% of Na+ and water
All nutrients
Ions
Small proteins
Movement via the
transcellular route
involves:
1 Transport across the
luminal membrane.
2 Diffusion through the
cytosol.
Lateral intercellular space
Tight junction
Filtrate
in tubule
lumen
The paracellular route
involves:
• Movement through
leaky tight junctions,
particularly in the PCT.
3 Transport across the basolateral
membrane. (Often involves the lateral
intercellular spaces because
membrane transporters transport ions
into these spaces.)
4 Movement through the interstitial
fluid and into the capillary.
Interstitial
fluid
Capillary
endothelial
cell
Tubule cell
Peritubular
capillary
Paracellular
H2O
2
1
3
4
Transcellular
Luminal
membrane
1
Transcellular
3
4
2
Solutes
3
4
Endothelium of peritubular capillaries
Paracellular
Basolateral
membranes
Active
transport
Passive
transport
Figure 25.13
Tubular Reabsorption
• Paracellular route
– Between cells
– Limited to water movement and reabsorption of
Ca2+, Mg2+, K+, and some Na+ in the PCT where
tight junctions are leaky
Tubular Reabsorption
• Sodium
– Most abundant cation in filtrate
– Primary active transport out of the tubule cell by
Na+-K+ ATPase in the basolateral membrane
– Na+ passes in through the luminal membrane by
secondary active transport or facilitated diffusion
mechanisms
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Tubular Reabsorption
1 At the basolateral membrane,
Na+
Nucleus
Filtrate
in tubule
lumen
Na+
Interstitial
fluid
Tubule cell
2
3Na+
3Na+
Glucose
Amino
acids
Some
ions
Vitamins
H2O
Lipid-soluble
substances
Cl–, Ca2+, K+
and other
ions, urea
1
2K+
2K+
3
K+
4
5
6
Primary active transport
Secondary active transport
Passive transport (diffusion)
Tight junction
Cl–
Paracellular
route
Peritubular
capillary
is pumped into the
interstitial space by the Na+-K+
ATPase. Active Na+ transport
creates concentration gradients
that drive:
2 “Downhill” Na+ entry at the
luminal membrane.
3 Reabsorption of organic
nutrients and certain ions by
cotransport at the luminal
membrane.
4 Reabsorption of water by
osmosis. Water reabsorption
increases the concentration of
the solutes that are left
behind. These solutes can
then be reabsorbed as
they move down their
concentration gradients:
5 Lipid-soluble
substances diffuse by the
transcellular route.
Transport protein
Ion channel or aquaporin
• Sodium
– Low hydrostatic pressure and high osmotic
pressure in the peritubular capillaries
• Promotes bulk flow of water and solutes (including Na+)
6 Cl– (and other anions),
K+, and urea diffuse by the
paracellular route.
Figure 25.14
Tubular Maximum
– Transport maximum (Tm) reflects the number of
carriers in the renal tubules available
– When the carriers are saturated, excess of that
substance is excreted
– Example: too much glucose in the blood entering
glomerulus will cause glucosuria
Tubular Reabsorption
• Reabsorption of nutrients, water and ions
– Blood becomes hypertonic to filtrate
– Water is reabsorbed by osmosis
– Cations and fat-soluble substances follow by
diffusion
Tubular Secretion
• Reabsorption in reverse
– K+, H+, NH4+, creatinine and organic acids move
from peritubular capillaries or tubule cells into
filtrate
– Involves active transport since no concentration
gradients in this case
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Na+ (65%)
Glucose
Amino acids
H2O (65%) and
many ions (e.g.
Cl– and K+)
Milliosmols
Tubular Secretion
Cortex
(d)
(a)
300
(e)
Outer
medulla
(b)
600
Some
drugs
–
H+, HCO3
NH4+
• Foreign substances (penicillin and other drugs)
• Nitrogenous wastes
• Excess K+
Inner
medulla
Blood pH regulation
(a) Proximal convoluted tubule:
• 65% of filtrate volume reabsorbed
• Na+, glucose, amino acids, and other nutrients actively
transported; H2O and many ions follow passively
• H+ and NH4+ secretion and HCO3– reabsorption to
maintain blood pH (see Chapter 26)
• Some drugs are secreted
• Principle effects
– Rids body of
(c)
– Controls blood pH:
1200
• Altering amounts of H+ or HCO3– in urine
Active transport
(primary or
secondary)
Passive transport
Figure 25.18a
Variations in Urine Formation
• Composition varies
– Fluid volume
– Solute concentration
Variations in Urine Formation
• Water intake must equal water loss
– Kidney regulates water loss by producing:
• Hypotonic urine (dilute)
• Hypertonic urine (concentrated)
Osmolality
of interstitial
fluid
(mOsm)
Countercurrent Mechanism
• Role of countercurrent mechanisms
– Establish and maintain an osmotic gradient
– Creates hypertonic interstitial fluid within kidney
medulla
– Hypertonic interstitial fluid allows the kidneys to
vary urine concentration
Active transport
H2O
NaCI
H2O
NaCI
H2O
NaCI
H2O
NaCI
Cortex
Passive transport
Water impermeable
Countercurrent multiplier
The long loops of Henle of the
juxtamedullary nephrons
create the medullary
osmotic gradient.
Outer
medulla
H2O
NaCI
H2O
H2O
Inner
medulla
Loop of Henle
Figure 25.16a
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Active transport
Passive transport
Formation of Concentrated Urine
Collecting duct
H2O
Descending limb
of loop of Henle
• Depends on the medullary osmotic gradient
and the ability to alter permeability of the
collecting tubules
DCT
H2O
Cortex
H2O
NaCI
H2O
osmolarity of extracellular fluid (also
plasma volume)
H2O
NaCI
Outer
medulla
ADH release
H2O
Urea
NaCI
aquaporins in collecting duct
H2O
Urea
H2O
Inner
medulla
H2O reabsorption in collecting duct
H2O
(b) Maximal ADH
Small volume of concentrated urine
Small volume of
concentrated urine
Figure 25.17b
Active transport
Passive transport
Formation of Dilute Urine
Collecting duct
• Filtrate is diluted in the ascending Loop of Henle
• In the absence of ADH, dilute filtrate continues into the renal
pelvis as dilute urine
Descending limb
of loop of Henle
DCT
Cortex
NaCI
osmolarity of extracellular fluid
H2O
ADH release
NaCI
Outer
medulla
NaCI
aquaporins in collecting duct
H2O reabsorption in collecting duct
H2O
Urea
Inner
medulla
(a) Absence of ADH
Large volume
of dilute urine
Large volume of dilute urine
Acid-Base Balance
• pH affects all functional proteins and
biochemical reactions in the body
– Regulation prevents changes in body’s internal environment
• Alkalosis or alkalemia: arterial blood pH >7.45
• Acidosis or acidemia: arterial pH < 7.35
Figure 25.17a
Acid-Base Balance
• Concentration of hydrogen ions is regulated by
1. Chemical buffer systems in blood
• Rapid, first line of defense
2. Brainstem respiratory centers
• Acts within 1–3 minutes
3. Renal mechanisms
• Most potent
• Requires hours to days to affect pH changes
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Acid-Base Balance
Acid-Base Balance
• Most important renal mechanisms:
– Blood
– Conserving (reabsorbing) HCO3–
– Excreting HCO3–
– Secretion of H+
• CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+
– Lungs
• Regulate carbonic acid levels by CO2 manipulation
• H+ secretion occurs in the PCT and in collecting tubules
– Kidneys
• Selectively secrete and reabsorb to maintain pH
Acid-Base Balance
• Examples
– Respiratory Acidosis
• Lungs are unable to eliminate CO2 adequately
• Kidneys reabsorb HCO3–, secrete H + (and NH4 +)
– Respiratory Alkalosis
• CO2 levels are low
• Kidneys secrete HCO3–, retain H + (and NH4 +)
1 CO2 combines with water
within the tubule cell,
forming H2CO3.
3bFor each H+ secreted, a HCO3– enters the
peritubular capillary blood either via symport
with Na+ or via antiport with CI–.
2 H2CO3 is quickly split,
forming H+ and bicarbonate
ion (HCO3–).
4 Secreted H+ combines with HCO3– in the
filtrate, forming carbonic acid (H2CO3). HCO3–
disappears from the filtrate at the same rate
that HCO3– (formed within the tubule cell)
enters the peritubular capillary blood.
3aH+ is secreted into the filtrate.
Nucleus
Filtrate in
tubule lumen
Peritubular
capillary
PCT cell
2K+
2K+
ATPase
3Na+
HCO3– + Na+
3Na+
Cl–
Cl–
HCO3–
3a
H+
HCO3–
4
H+
*
5
HCO3–
2
ATPase
H2CO3
3b
HCO3–
H2CO3
1
Na+
CO2
6 CO2 diffuses
into the tubule
cell, where it
triggers further H+
secretion.
Na+
CA
6
H2O
5 The H2CO3
formed in the
filtrate dissociates
to release CO2
and H2O.
CO2
+
H2O
CO2
Tight junction
Primary active
transport
Secondary active
transport
Simple diffusion
Transport protein
Carbonic anhydrase
Figure 26.12
Variations in Blood Pressure
Variations in Blood Pressure
• Activity of kidney related to variations in blood
pressure
• Renal mechanisms influencing blood pressure
– Blood pressure and blood volume are related
– Blood volume is controlled by
• Solute concentration
• Water regulation
– ADH
• Water
– Renin-angiotensin mechanism
• Sodium
• Potassium
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Antidiuretic Hormone (ADH)
Aldosterone
• Produced in adrenal cortex in response to…
• Plasma osmolarity
– Low blood volume
– Low blood pressure
– Low plasma Na +
– High plasma K +
Increases (what could cause this?)
Osmoreceptors stimulated
Thirst & ADH secretion
• Stimulates K+ secretion and Na+ reabsorption
• Changes in plasma sodium levels affect…
Water reabsorption (decreased urine output)
Increased blood volume
– Plasma volume
– Blood pressure
Increased blood pressure
Aldosterone
Aldosterone
• Regulation of sodium balance
• Renin-angiotensin mechanism is the main
trigger for aldosterone release
– Na+ reabsorption
• 65% is reabsorbed in the proximal tubules
• 25% is reclaimed in the Loops of Henle
– Granular cells of JGA secrete renin in response to
• Sympathetic nervous system stimulation
• ↓ Filtrate osmolality (decreased sodium)
• ↓ Stretch (due to ↓ blood pressure)
– Aldosterone causes active reabsorption of
remaining Na+ in DCT and collecting ducts
– Water follows Na+
– How would this affect blood volume and blood
pressure?
Efferent
arteriole
Glomerular capsule
Glomerulus
Afferent
arteriole
Parietal layer
of glomerular
capsule
Capsular
space
Aldosterone
Foot processes
of podocytes
Red blood cell
Proximal
tubule cell
Efferent
arteriole
Juxtaglomerular
apparatus
• Macula densa cells
of the ascending limb
of loop of Henle
• Extraglomerular
mesangial cells
• Granular cells
Lumens of
glomerular
capillaries
Endothelial cell
of glomerular
capillary
Mesangial cells
between capillaries
Afferent arteriole
Juxtaglomerular
apparatus
Podocyte cell
body (visceral
layer)
• Renin catalyzes the production of angiotensin
II
– Prompts aldosterone release from the adrenal
cortex
• Targets cells of DCT and collecting ducts
• Initiates sodium reabsorption
– Causes systemic vasoconstriction
– Effect on BP?
Renal corpuscle
Figure 25.8
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K+ (or Na+) concentration
in blood plasma*
Blood Pressure Control
Renin-angiotensin
mechanism
Stimulates
• 3 main mechanisms
Adrenal cortex
Negative
feedback
inhibits
– Renin-angiotensin system
– Neural regulation (sympathetic control)
– ADH release
Releases
Aldosterone
Targets
Kidney tubules
Effects
Na+ reabsorption
K+ secretion
Restores
Homeostatic plasma
levels of Na+ and K+
Figure 26.8
Systemic
blood pressure/volume
Filtrate NaCl concentration in
ascending limb of loop of Henle
Stretch in afferent
arterioles
(+)
Factors Affecting Urine Volume
Inhibits baroreceptors
in blood vessels
(+)
(+)
(+)
• Increased temperature
Sympathetic
nervous system
Granular cells of kidneys
Release
(+)
Renin
Systemic arterioles
Angiotensin I
Angiotensinogen
(from liver)
– Increases vasodilation and perspiration
– Decreases blood flow to kidneys
Causes
Catalyzes conversion
Vasoconstriction
Results in
Converting enzyme (in lungs)
(+)
Peripheral resistance
Angiotensin II
Posterior pituitary
• Decreased temperature
(+)
(+)
Releases
(+)
Systemic arterioles
Adrenal cortex
ADH (antidiuretic
hormone)
– Increases blood flow to kidneys
Secretes
Causes
(+)
Vasoconstriction
Aldosterone
Results in
Peripheral resistance
Targets
Collecting ducts
of kidneys
Causes
Distal kidney tubules
Causes
H2O reabsorption
Na+ (and H2O)
reabsorption
Results in
Blood volume
(+) stimulates
Blood pressure
Renin-angiotensin system
Neural regulation (sympathetic
nervous system effects)
ADH release and effects
Figure 26.10
Diuretics
Factors Affecting Urine Output
• Chemicals that increase urine output
– Osmotic diuretics
• Substances not reabsorbed
– Glucose in a diabetic patient
– ADH inhibitors
• Alcohol and water
– Substances that inhibit Na+ reabsorption
• Caffeine, thiazides (class of medications), loop diuretics
(inhibit Na+-K+-Cl- symport proteins)
•
•
•
•
↑ blood pressure
↑ blood solute concentration
↓ plasma proteins
Psychological factors
– Potassium levels are affected by some diuretics
• Can be extremely dangerous
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