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Chapter 17

Physiology
of the
Kidneys

I. Structure and Function of


the Kidneys

A. Kidney Functions
1. Regulation of the extracellular fluid environment in
the body, including:
a. Volume of blood plasma (affects blood pressure)
b. Wastes
c. Electrolytes
d. pH

B. Gross structure of the urinary system


1. Introduction
a. Urine made in the kidney drains into the renal pelvis,
then down the ureter to the urinary bladder.
b. It passes from the bladder through the urethra to exit the
body.
c. Urine is transported using peristalsis.

Organs of the urinary system


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Inferior
vena cava
Kidney
Renal artery
Renal vein

Renal vein
Renal artery
Abdominal
aorta
Ureter

Urinary
bladder
Urethra

2. Kidney Structure
a. The kidney has two distinct regions:
1) Renal cortex
2) Renal medulla, made up of renal pyramids and
columns
b. Each pyramid drains into a minor calyx major
calyx renal pelvis.

Radiograph of the urinary system


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Twelfth
thoracic
vertebra
Twelfth
rib
Minor
calyx
Renal
pelvis
Kidney
Ureter

Urinary
bladder
SPL/Photo Researchers

C. Control of Micturition
1. Detrusor muscles line the wall of the urinary
bladder.
a. Gap junctions connect smooth muscle cells.
b. Innervated by parasympathetic neurons, which
release acetylcholine onto muscarinic ACh
receptors
2. Sphincters surround urethra.
a. Internal urethral sphincter: smooth muscle
b. External urethral sphincter: skeletal muscle

Control of Micturition, cont


3. Stretch receptors in the bladder send information
to S2S4 regions of the spinal cord.
a. These neurons normally inhibit parasympathetic
nerves to the detrusor muscles, while somatic
motor neurons to the external urethral sphincter
are stimulated.
b. Called the guarding reflex
c. Prevents involuntary emptying of bladder

Control of Micturition, cont


4. Stretch of the bladder initiates the voiding reflex.
a. Information about stretch passes up the spinal
cord to the micturition center of the pons.
b. Parasympathetic neurons cause detrusor
muscles to contract rhythmically
c. Inhibition of sympathetic innervation of the
internal urethral sphincter causes it to relax.
d. Person feels the need to urinate and can control
when with external urethral sphincter.

D. Microscopic Kidney Structure


1. Nephron: functional unit of the kidney
a. Each kidney has more than a million nephrons.
b. Nephron consists of small tubules and
associated blood vessels.
c. Blood is filtered, fluid enters the tubules, is
modified, then leaves the tubules as urine

Kidney Structure
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Renal cortex

Renal medulla
Renal
cortex

Minor calyx

Renal column

Renal pelvis

Nephron

Major calyx

Renal pyramid

Renal
artery
Renal
vein

Renal
medulla

Ureter
Renal papilla

Renal
papilla
(a)

Minor calyx
(b)
Glomerular
capsule

Distal
convoluted
tubule

Collecting
duct

Proximal
convoluted
tubule

Loop of Henle

(c)

2. Renal Blood Vessels


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Renal artery
Interlobar arteries
Arcuate arteries
Interlobular arteries
Afferent arterioles
Glomerulus
Efferent arterioles
Peritubular capillaries
Interlobular veins
Arcuate veins
Interlobar veins
Renal vein

Interlobular artery
and vein
Renal cortex
Arcuate artery
and vein
Interlobar artery
and vein
Renal medulla
Renal artery
Renal pelvis
Renal vein

Ureter

3. Nephron Tubules
a.

b.
c.
d.
e.
f.

Glomerular (Bowmans) capsule surrounds the


glomerulus. Together, they make up the renal
corpuscle.
Filtrate produced in renal corpuscle passes into the
proximal convoluted tubule.
Next, fluid passes into the descending and ascending
limbs of the loop of Henle.
After the loop of Henle, fluid passes into the distal
convoluted tubule.
Finally, fluid passes into the collecting duct.
The fluid is now urine and will drain into a minor calyx.

Nephron Tubules & Associated Blood Vessels


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Peritubular capillaries

Distal convoluted tubule

Glomerulus
Glomerular capsule
Efferent arteriole
Afferent arteriole
Interlobular artery
Proximal
convoluted
tubule

Interlobular vein

Arcuate artery
and vein
Interlobar
artery and vein

Peritubular
capillaries
(vasa recta)
Nephron loop
(of Henle)

Descending
limb
Ascending
limb

Collecting
duct

4. Two Types of Nephrons


a. Juxtamedullary: better at making concentrated
urine
b. Cortical
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Cortical
nephron
Juxtamedullary
nephron

Renal cortex

(a)

Renal medulla

Glomerulus
Blood
flow
(b)
Collecting duct

II. Glomerular Filtration

A. Glomerular Corpuscle
1. Capillaries of the glomerulus are fenestrated.
a. Large pores allow water and solutes to leave but
not blood cells and plasma proteins.
2. Fluid entering the glomerular capsule is called
filtrate

Glomerular Corpuscle, cont


3. Filtrates must pass through:
a. Capillary fenestrae
b. Glomerular basement membrane
c. Visceral layer of the glomerular capsule
composed of cells called podocytes with
extensions called pedicles

Glomerular Capillaries & Capsule


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Podocyte
cell body

Primary
process of
podocyte
Branching
pedicels

Professor P.M. Motta and M. Sastellucci/SPL/Photo Researchers

Glomerular Corpuscle & Filtration Barrier


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Glomerulus
Proximal convoluted tubule
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Afferent
arteriole

Glomerular (Bowmans) capsule

Blood
flow

Podocyte of visceral layer


of glomerular capsule

Foot
processes

Efferent
arteriole

Slit diaphragm

Parietal layer of
glomerular capsule

Fenestrae

Filtrate
Pedicel
(foot
process)

Basement membrane
Fenestrae
Capillary endothelium
Glomerular basement
membrane
Slit diaphragm
Podocyte foot process

Filtration
slits

Capillary lumen
Plasma

Fenestra
Erythrocyte
Donald Fawcett & D. Friend/Visuals Unlimited, Inc

Glomerular Corpuscle, cont


d. Slits in the pedicles called slit diaphragm pores are
the major barrier for the filtration of plasma
proteins.
1) Defect here causes proteinuria = proteins in
urine.
2) Some albumin is filtered out but is reabsorbed
by active endocytosis.

B. Glomerular Ultrafiltrate
1. Fluid in glomerular capsule gets there via
hydrostatic pressure of the blood, colloid osmotic
pressure, and very permeable capillaries.
2. These forces produce a net filtration pressure of
about 10mmHg

Formation of Glomerular Ultrafiltrate


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Glomerular
(Bowmans)
capsule

Protein

Afferent
arteriole

Other
solutes
Glomerular
ultrafiltrate
Efferent
arteriole

3. Filtration Rates
a. Glomerular filtration rate (GFR): volume of filtrate
produced by both kidneys each minute = 115125
ml.
1) 180 L/day (~45 gal)
2) Total blood volume is filtered every 40 minutes
3) Most must be reabsorbed immediately

C. Regulation of Glomerular Filtration Rate


1. Vasoconstriction or dilation of afferent arterioles
changes filtration rate.
a. Extrinsic regulation via sympathetic nervous
system
b. Intrinsic regulation via signals from the kidneys;
called renal autoregulation

2. Sympathetic Nerve Effects


a. In a fight/flight reaction, there is vasoconstriction of
the afferent arterioles.
b. Helps divert blood to heart and muscles
c. Urine formation decreases to compensate for the
drop in blood pressure

Sympathetic Nerve Effects


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Stimuli
Blood pressure

Exercise

Baroreceptor reflex

Sympathetic
nerve activity

Vasoconstriction
in skin, GI tract
Cardiac
output

Vasoconstriction
of afferent arterioles
in kidneys

GFR

Total
peripheral
resistance

Urine
production

Blood volume
Negative feedback corrections

3. Renal Autoregulation
a. GFR is maintained at a constant level even when
blood pressure (BP) fluctuates greatly.
1) Afferent arterioles dilate if BP < 70.
2) Afferent arterioles constrict if BP > normal.
b. Myogenic constriction: Smooth muscles in
arterioles sense an increase in blood pressure.

Renal Autoregulation, cont


c. Tubuloglomerular feedback: Cells in the
ascending limb of the loop of Henle called
macula densa sense a rise in water and
sodium as occurs with increased blood
pressure (and filtration rate).
1) They send a chemical signal (ATP) to
constrict the afferent arterioles.

Regulation of Glomerular Filtration Rate

III. Reabsorption of Salt and


Water

A. Introduction
1. Reabsorption return of filtered molecules to the
blood
2. 180 L of water is filtered per day, but only 12 L is
excreted as urine.
a. This will increase when well hydrated and
decrease when dehydrated.
b. A minimum 400 ml must be excreted to rid the
body of wastes = obligatory water loss.
c. 85% of reabsorption occurs in the proximal
tubules and descending loop of Henle. This
portion is unregulated.

Filtration and Reabsorption


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Reabsorption

Filtration

Glomerular
(Bowmans) capsule

Glomerulus

B. Reabsorption in the Proximal Tubule

1. The osmolality of filtrate in the glomerular capsule


is equal to that of blood plasma (isoosmotic).
2. Na+ is actively transported out of the filtrate into
the peritubular blood to set up a concentration
gradient to drive osmosis.

3. Active Transport
a. Cells of the proximal tubules are joined by tight
junctions on the apical side (facing inside the
tubule).
b. The apical side also contains microvilli.
c. These cells have a lower Na+ concentration than
the filtrate inside the tubule due to Na+/K+ pumps
on the basal side of the cells and low permeability
to Na+.
d. Na+ from the filtrate diffuses into these cells and is
then pumped out the other side.

4. Passive Transport
a. The pumping of sodium into the interstitial space
attracts negative Cl out of the filtrate.
b. Water then follows Na+ and Cl into the tubular
cells and the interstitial space.
c. The salts and water diffuses into the peritubular
capillaries.

Salt and Water Reabsorption in the Proximal Tubule


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Reabsorption
Na+
H2O follows
Cl
transport transport salt by
(passive) (active)
osmosis

Fluid reduced to
1/ original volume,
3
but still isosmotic

Filtration
Glomerular
(Bowmans)
capsule

5. Significance of proximal tubule reabsorption


a. 65% of the salt and water is reabsorbed, but that is
still too much filtrate
b. An additional 20% of water is reabsorbed through
the descending limb of the Loop of Henle.
1) Happens continuously and is unregulated
2) The final 15% of water (~27 L) is absorbed later
in the nephron under hormonal control.
3) Fluid entering loop of Henle is isotonic to
extracellular fluids.

C. Countercurrent Multiplier System


1. Water cannot be actively pumped out of the tubes,
and it will not cross if isotonic to extracellular fluid.
a. The structure of the loop of Henle allows for a
concentration gradient to be set up for the
osmosis of water.
b. The ascending portion sets up this gradient.

2. Ascending Limb of the Loop of Henle


a. Salt (NaCl) is actively pumped into the interstitial
fluid from the thick segment of the limb
1) Movement of Na+ down its electrochemical
gradient from filtrate into tubule cells powers the
secondary active transport of Cl and K+.
2) Na+ is moved into interstitial space via Na+/K+
pump. Cl follows Na+ passively due to electrical
attraction, and K+ passively diffuses back into
filtrate.

Transport of Ions in the Ascending Limb of the


Loop of Henle
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Ascending limb of loop

Filtrate
(tubular
lumen)

Interstitial
space

Apical
membrane
2 Cl

Na+
2 Cl

Na+

ATP
ADP
K+

Na+

K+

Na+
K+

K+

K+

K+

Cl

K+

Cl

Cl
Cl
Basolateral
membrane

Ascending Limb of the Loop of Henle, cont


b. Walls are not permeable to water, so osmosis
cannot occur from the ascending part of the loop.
c. Surrounding interstitial fluid becomes increasingly
solute concentrated at the bottom of the tube.
d. Tubular fluid entering the descending loop of
Henle becomes more hypotonic as it descends the
loop.

3. Descending Limb of the Loop of Henle


a. Is not permeable to salt but is permeable to water
b. Water is drawn out of the filtrate and into the
interstitial space where it is quickly picked up by
capillaries.
c. As it descends, the fluid becomes more solute
concentrated.
1) This is perfect for salt transport out of the fluid in
the ascending portion.

Countercurrent Multiplier System


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Loop of Henle

400

300
mOsm

Cortex

800

2
H2O
H2O

600

1
Na+Cl

Na+Cl

Na+Cl

Na+Cl

Na+Cl

Na+Cl

Na+Cl
1,000

Capillary

Na+Cl
1,000

H2O

800

600

Medulla

1,400
Descending limb

Ascending limb

Passively permeable
to water

Active transport of Na+,


Cl follows passively;
impermeable to water

4. Countercurrent Multiplication
a. Positive feedback mechanism is created between
the two portions of the loop of Henle.
1) The more salt the ascending limb removes, the
saltier the fluid entering it will be (due to loss of
water in descending limb).

b. Steps of countercurrent mechanism


1) Interstitial fluid is hypertonic due to NaCl pumped
out of the ascending limb
2) Water leaves descending limb by osmosis, making
the filtrate hypertonic going into the ascending limb
3) More NaCl in the ascending limb can now be
pumped out into the interstitial fluid
4) The greater concentration of the interstitial fluid
draws more water from the descending limb
5) Filtrate in ascending limb now more concentrated
6) Continues until the maximum NaCl concentration
of the inner medulla is reached.

c. Vasa Recta
1) Specialized blood vessels around loop of Henle,
which also have a descending and ascending
portion
2) Help create the countercurrent system because
they take in salts in the descending region but lose
them again in the ascending region
a) Keep salts in the interstitial space

Vasa Recta, cont


3) High salt concentration (oncotic pressure) at the
beginning of the ascending region pulls in water,
which is removed from the interstitial space.
a) Also keeps salt concentration in the interstitial
space high
4) There are also urea transporters and aquaporins
to aid in the countercurrent exchanges

Countercurrent Exchange in the Vasa Recta


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Blood flow
Renal
cortex

Capillary

Tissue fluid
300
350

475

425

625

575

775

725

925

875

1,025

Diffusion of NaCl and urea


Osmosis of water

Outer renal
medulla

1,075

1,200

Inner renal
medulla

5. Effects of Urea
a. Urea is a waste product of protein metabolism
b. Contributes to countercurrent system
1) Transported out of collecting duct and into
interstitial fluid
2) Diffuses back into ascending limb and cycles
around continuously
3) Helps set up solute concentration gradients

Role of Urea in Urine Concentration


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Distal tubule
Cortex

H2O

Outer
medulla

H2O

Collecting
duct
H2O

Inner
medulla

H2O
H2O

2
1

H2O
3
NaCl

H2O

Urea
Water

Loop of Henle

Renal Tubule Transport Properties

Renal Tubule Osmolality


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Proximal
tubule

Distal
tubule
100
300

Collecting
duct
Cortex

300
300

320
100

Vasa recta

H2 O
200
400
400

400

400

400
Outer medulla
H2 O

600
Descending
limb of loop

600

600

H2 O

800

800

Ascending
limb of loop

800

800

800
Inner medulla
H2 O

1,200

1,200

1,400

1,200

1,400

1,400

H2 O

D. Collecting Duct and ADH


1. Last stop in urine formation
2. Impermeable to NaCl but permeable to water
a. Also influenced by hypertonicity of interstitial
space water will leave via osmosis if able to
b. Permeability to water depends on the number of
aquaporin channels in the cells of the collecting
duct
c. Availability of aquaporins determined by ADH
(antidiuretic hormone)

Collecting Duct and ADH, cont


3. ADH binds to receptors on collecting duct cells
cAMP Protein kinase Vesicles with
aquaporin channels fuse to plasma membrane.
a) Water channels are removed without ADH.
4. ADH is produced by neurons in the hypothalamus
but stored and released from the posterior
pituitary gland
a) Release stimulated by an increase in blood
osmolality

ADH Stimulation of Aquaporin Channels


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Extracellular
fluid

Cytoplasm
ADH

Vesicle
Aquaporin
channels
(a)

Fusion of exocytotic vesicle


(b)

No
ADH

ADH

Plasma membrane with


aquaporin channels
No
ADH
Formation of
endocytotic vesicle
(d)

(c)

Homeostasis of Plasma Concentration by ADH


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Stimulus

Stimulus

Low water intake


(dehydration)

High water intake


(over-hydration)

Plasma
osmolality

Plasma
osmolality
Osmoreceptors in
hypothalamus

Sensor
Integrating center
Effector

Posterior pituitary

ADH

ADH
Kidneys

Negative
feedback
correction

Water
reabsorption

Water
reabsorption

Less water
excreted in urine

More water
excreted in urine

Negative
feedback
correction

ADH Secretion and Action

IV. Renal Plasma Clearance

A. Transport processes affecting renal clearance


1. Kidneys must also remove excess ions and wastes
from the blood.
a. Sometimes called renal clearance
b. Filtration in the glomerular capsule begins this
process.
c. Reabsorption returns some substances to the
blood (decreases renal clearance)
d. Secretion finishes the process when substances
are moved from the peritubular capillaries into
the tubules. (increases renal clearance)

2. Excretion Rate
a. Excretion rate = (filtration rate + secretion rate)
reabsorption rate
b. Used to measure glomerular filtration rate
(GFR), an indicator of renal health

Secretion is the reverse of reabsorption

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Secretion

Excretion

Reabsorption

Filtration

3. Secretion of Drugs
a. Membrane carriers specific to foreign substances
transport them into the tubules.
b. Called organic anion transporters (OATs) or
organic cation transporters (OCTs)
c. Carriers are polyspecific overlap in function
d. Very fast; may interfere with action of therapeutic
drugs

B. Clearance of Inulin
1. Inulin is a compound found in garlic, onion,
dahlias, and artichokes.
a. Great marker of glomerular filtration rate
because it is filtered but not reabsorbed or
secreted
VXU

GFR = ---------P
V = rate of urine formation
U = inulin concentration in urine
P = inulin concentration in plasma

Renal Clearance of Inulin


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Inulin

(a)

(b)
To peritubular
capillaries
Renal artery
with inulin

Renal vein
inulin concentration lower
than in renal artery

(c)

Ureter
urine containing all
inulin that was filtered

2. Renal Plasma Clearance Calculation


a. Volume of plasma from which a substance is
completely removed by the kidneys in 1 minute
1) Inulin is filtered only. Clearance = GFR
2) Anything that can be reabsorbed has a
clearance < GFP.
3) If a substance is filtered and secreted, it will
have a clearance > GFR.
4) Renal plasma clearance uses same formula as
GFR.
b. Clearance of urea is less than GFR means some
is reabsorbed

Renal Plasma Clearance

C. Clearance of PAH
1.

2.
3.
4.

Not all blood delivered to the glomeruli is filtered in each


pass, so blood must make several passes to completely
clear a substance.
PAH (para-aminohippuric acid) is an exogenous molecule
injected for measurement of total renal blood flow.
Substances not filtered must be secreted into the tubules
by active transport from the peritubular capillaries
All PAH in the peritubular capillaries will be secreted by
OATs, so the time it takes to clear all PAH injected
indicates blood flow to these capillaries.

Renal Clearance of PAH


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PAH

Filtration

(a)
To peritubular
capillaries

Renal artery
containing PAH

Renal vein
almost no PAH

Peritubular capillaries
To renal vein
(c)

Filtration plus
secretion
(d)

Ureter
urine containing almost
all PAH that was in
renal artery

D. Reabsorption of Glucose
1. Glucose (and amino acids) is easily filtered out into
the glomerular capsule
2. Completely reabsorbed in the proximal tubule via
secondary active transport with sodium, facilitated
diffusion, and simple diffusion

Mechanism of Reabsorption in the proximal tubule


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Lumen of
kidney tubule

Glucose

Apical
membrane

Na+

Cotransport

Proximal
tubule cell
Basolateral
membrane
ATP
ADP

3
K+

Facilitated
diffusion

2
Simple
diffusion

Primary active
transport

Glucose

K+
Na+

Capillary

Reabsorption of Glucose, cont


3. Glucose/Na+ cotransporters have a transport
maximum (Tm).
a. If there is too much glucose in the filtrate, it will
not be completely reabsorbed because all the
carriers are in use (saturated).
b. Extra glucose spills over into the urine =
glycosuria and is a sign of diabetes mellitus.
c. Extra glucose in the blood also results in
decreased water reabsorption and possible
dehydration.

V. Renal Control of Electrolyte


and Acid-Base Balance

A. Introduction
1. Kidneys match electrolyte (Na+, K+, Cl,
bicarbonate, phosphate) excretion to ingestion.
a. Control of Na+ levels is important in blood
pressure and blood volume.
b. Control of K+ levels is important in healthy
skeletal and cardiac muscle activity.
c. Aldosterone plays a big role in Na+ and K+
balance.

B. Role of Aldosterone in Na+/K+ Balance


1. About 90% of filtered Na+ and K+ is reabsorbed
early in the nephron.
a. This is not regulated.
2. An assessment of what the body needs is made,
and aldosterone controls additional reabsorption of
Na+ and secretion of K+ in the distal tubule and
collecting duct.

3. Potassium Secretion
a. Aldosterone independent response: Increase in
blood K+ triggers an increase in the number of K+
channels in the cortical collecting duct.
1) When blood K+ levels drop, these channels are
removed.
b. Aldosterone-dependent response: Increase in
blood K+ triggers adrenal cortex to release
aldosterone.
1) This increases K+ secretion in the distal tubule
and collecting duct.

Potassium is Reabsorbed and Secreted


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Filtered

Reabsorbed
Secreted
K+
K+

Cortical portion
of collecting duct

K+
Proximal
convoluted
tubule

Excreted

c. Sodium and Potassium


1) Increases in sodium absorption drive extra
potassium secretion.
2) Due to:
a) Potential difference created by Na+ reabsorption
driving K+ through K+ channels
b) Stimulation of renin-angiotensin-aldosterone
system by water and Na+ in filtrate
c) Increased flow rates bend cilia on the cells of
the distal tubule, resulting in activation of K+
channels

4. Control of Aldosterone Secretion

a. A rise in blood K+ directly stimulates production of


aldosterone in the adrenal cortex.
b. A fall in blood Na+ indirectly stimulates production
of aldosterone via the renin- angiotensinaldosterone system.

C. Juxtaglomerular Apparatus
1. Located where the afferent arteriole comes into
contact with the distal tubule
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Glomerulus
Glomerular
capsule

Glomerulus

Region of the
juxtaglomerular
apparatus
Afferent
arteriole

Afferent
arteriole

Distal
tubule
Efferent
arteriole

Granular
cells

Macula
densa

Efferent
arteriole

Loop of Henle
(a)

(b)

Thick
ascending limb

Juxtaglomerular
apparatus

Juxtaglomerular Apparatus, cont


2. A decrease in plasma Na+ results in a fall in
blood volume.
a. Sensed by juxtaglomerular apparatus
b. Granular cells secrete renin into the afferent
arteriole.
c. This converts angiotensinogen into
angiotensin I.
d. Angiotensin-converting enzyme (ACE)
converts this into angiotensin II.

Juxtaglomerular Apparatus
3. Stimulates adrenal cortex to make aldosterone
a. Promotes the reabsorption of Na+ from cortical
collecting duct
b. Promotes secretion of K+
c. Increases blood volume and raises blood
pressure

4. Regulation of Renin Secretion


a. Low salt levels result in lower blood volume due to
inhibition of ADH secretion.
1) Less water is reabsorbed in collecting ducts and
more is excreted in urine.
b. Reduced blood volume is detected by granular
cells that act as baroreceptors. They then secrete
renin.
1) Granular cells are also stimulated by
sympathetic innervation from the baroreceptor
reflex.

Homeostasis of Plasma Na+


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Sensor
Integrating
center
Effector

Stimulus
Low Na+
intake

Negative feedback correction

Na+ retention
in blood

Na+ concentration

Na+ reabsorption in
cortical collecting duct

Hypothalamus

Aldosterone

Posterior pituitary

Adrenal cortex

ADH

Angiotensin II

Water reabsorption
in collecting ducts

Renin

Low plasma

Urine volume

Blood volume

Sympathetic
nerve activity

Juxtaglomerular apparatus

5. Macula Densa
a. Part of the distal tubule that forms the
juxtaglomerular apparatus
b. Sensor for tubuloglomerular feedback needed for
regulation of glomerular filtration rate
1) When there is more Na+ and H2O in the filtrate,
a signal is sent to the afferent arteriole to
constrict limiting filtration rate.
2) Controlled via negative feedback

Macula Densa, cont


c. When there is more Na+ and H2O in the filtrate, a
signal is sent to the afferent arteriole to inhibit the
production of renin.
1) This results in less reabsorption of Na+, allowing
more to be excreted.
2) This helps lower Na+ levels in the blood.

D. Atrial Natriuretic Peptide


1. Increases in blood volume also increase the
release of atrial natriuretic peptide hormone from
the atria of the heart when atrial walls are
stretched.
2. Stimulates kidneys to excrete more salt and
therefore more water
3. Decreases blood volume and blood pressure

Regulation of Renin and Aldosterone Secretion

E. Relationship Between Na+, K+, and H+


1. Reabsorption of Na+ stimulates the secretion of
other positive ions; K+ and H+ compete.
2. Acidosis stimulates the secretion of H+ and inhibits
the secretion of K+ ions; acidosis can lead to
hyperkalemia.
3. Alkalosis stimulates the secretion and excretion of
more K+.
4. Hyperkalemia stimulates the secretion of K+ and
inhibits secretion of H+; can lead to acidosis

Reabsorption of Na+ and Secretion of K+, and H+


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Peritubular capillaries
Blood
Na+

Na+
Na+

Na+

K+ or H+

H+
Na+

K+/H+

Na+

K+

K+
K+

Distal tubule
Cortical collecting duct

Na+

Na+
H+
Na+

Na+
K+
Na+

Na+

Ascending limb
of Henles loop

Medullary
collecting
duct

F. Acid-Base Regulation
1. Kidneys maintain blood pH by reabsorbing
bicarbonate and secreting H+; urine is thus acidic.
2. Proximal tubule uses Na+/H+ pumps to exchange
Na+ out and H+ in.
a. Some of the H+ brought in is used for the
reabsorption of bicarbonate.
b. Antiport secondary active transport

Acid-Base Regulation, cont


3. Bicarbonate cannot cross the inner tubule
membrane so must be converted to CO2 and H2O
using carbonic anhydrase.
a. Bicarbonate + H+ carbonic acid
b. Carbonic acid (w/ carbonic anhydrase)
H2O + CO2
c. CO2 can cross into tubule cells, where the
reaction reverses and bicarbonate is made
again.
d. This diffuses into the interstitial space.

Acidification of the Urine


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HCO3

Na

Proximal tubule

HCO3

ATPase
CA
H2CO3

Na

Distal tubule
H2O + CO2

Na+

H+

Blood

CA

Na

HCO3

Filtration

Lumen

Proximal tubule cell

+ H

Na+
H2O + CO2

H2CO3

HPO4

NH3

H2PO4
+

NH4

Acid-Base Regulation, cont

4. Aside from the Na+/H+ pumps in the proximal


tubule, the distal tubule has H+ ATPase pumps to
increase H+ secretion.

5. pH Disturbances
a. Kidneys can help compensate for respiratory
problems
b. Alkalosis: Less H+ is available to transport
bicarbonate into tubule cells, so less bicarbonate is
reabsorbed; extra bicarbonate secretion
compensates for alkalosis.

pH Disturbances, cont
c. Acidosis: Proximal tubule can make extra
bicarbonate through the metabolism of the amino
acid glutamine.
1) Extra bicarbonate enters the blood to
compensate for acidosis.
2) Ammonia stays in urine to buffer H+.

Disturbances of Acid-Base Balance

G. Urinary Buffers
1. Nephrons cannot produce urine with a pH
below 4.5.
2. To increase H+ secretion, urine must be
buffered.
a. Phosphates and ammonia buffer the urine.
b. Phosphates enter via filtration.
c. Ammonia comes from the deamination of
amino acids.

VI. Clinical Applications

A. Use of Diuretics
1. Used clinically to control blood pressure and
relieve edema (fluid accumulation)
a. Diuretics increase urine volume, decreasing
blood volume and interstitial fluid volume.
b. Many types act on different portions of the
nephron.

2. Types of Diuretics
a. Loop diuretics: most powerful; inhibit salt transport
out of ascending loop of Henle
1) Example: Lasix
2) Can inhibit up to 25% of water reabsorption
b. Thiazide diuretics: inhibit salt transport in distal
tubule
1) Can inhibit up to 8% of water reabsorption
c. Carbonic anhydrase inhibitors: much weaker;
inhibit water reabsorption when bicarbonate is
reabsorbed
1) Also promote excretion of bicarbonate

Types of Diuretics, cont


d. Osmotic diuretics: reduce reabsorption of water by
adding extra solutes to the filtrate
1) Example: Mannitol
2) Can occur as a side effect of diabetes
e. Potassium-sparing diuretics: Aldosterone
antagonists block reabsorption of Na+ and
secretion of K+.

Actions of Classes of Diuretics

Sites of Action of Clinical Diuretics


Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Carbonic
anhydrase
inhibitors

Proximal convoluted tubule

Na+

Cortex

Amino acids
Glucose
HCO3, PO43

Thick
ascending
limb

Distal convoluted tubule


Thiazide
diuretics

NaCl
H2O
Passive

(with ADH)
Potassium-sparing
diuretics

Glomerulus

H2O
no
ADH

Cortical
collecting
duct

Na+
Loop
diuretics

K+
Collecting
duct

Descending
limb
Medulla

Increasing
NaCl and urea
concentrations

H2O

H2O
(with ADH)

Ascending
limb

H2O
no
ADH

H2O

Urea
NaCl

Passive

Medullary
collecting
duct

B. Renal Function Tests


1. PAH and inulin clearance
a. Can diagnose nephritis or renal insufficiency
2. Urinary albumin excretion rate: detects abovenormal albumin excretion
a. Called microalbuminuria
b. Signifies renal damage due to hypertension or
diabetes
3. Proteinuria: overexcretion of proteins; signifies
nephrotic syndrome

C. Kidney Diseases
1. Acute Renal Failure
a. Ability of kidneys to regulate blood volume, pH,
and solute concentrations deteriorates in a
matter of hours/days.
b. Usually due to decreased blood flow through
kidneys due to:
1) Atherosclerosis of renal arteries
2) Inflammation of renal tubules
3) Use of certain drugs (NSAIDs)

2. Glomerulonephritis
a. Inflammation of the glomerulus
b. Autoimmune disease with antibodies produced in
response to streptococcus infection
c. Many glomeruli are destroyed, and others are
more permeable to proteins.
d. Loss of proteins from blood reduces blood osmotic
pressure and leads to edema.

3. Renal Insufficiency
a. Any reduction in renal activity
b. Can be caused by glomerulonephritis, diabetes,
atherosclerosis, or blockage by kidney stones
c. Can lead to high blood pressure, high blood K+
and H+, and uremia = urea in the blood.
d. Patients with uremia are placed on a dialysis
machine to clear blood of these solutes.

4. Dialysis
a. Artificial kidney
b. Hemodialysis blood cleansed of wastes as it
passes through dialysis fluid
c. CAPD continuous ambulatory peritoneal dialysis
dialysis fluid introduced to the abdominal cavity
where wastes can pass out of abdominal blood
vessels; fluid is then pumped out of the abdominal
cavity

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