Professional Documents
Culture Documents
Physiology
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
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.
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
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)
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.
Peritubular capillaries
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
Cortical
nephron
Juxtamedullary
nephron
Renal cortex
(a)
Renal medulla
Glomerulus
Blood
flow
(b)
Collecting duct
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
Podocyte
cell body
Primary
process of
podocyte
Branching
pedicels
Glomerulus
Proximal convoluted tubule
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Afferent
arteriole
Blood
flow
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
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
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
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.
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.
Reabsorption
Filtration
Glomerular
(Bowmans) capsule
Glomerulus
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.
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
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
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
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).
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
Blood flow
Renal
cortex
Capillary
Tissue fluid
300
350
475
425
625
575
775
725
925
875
1,025
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
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
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
Extracellular
fluid
Cytoplasm
ADH
Vesicle
Aquaporin
channels
(a)
No
ADH
ADH
(c)
Stimulus
Stimulus
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
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
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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
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
C. Clearance of PAH
1.
2.
3.
4.
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
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
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.
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.
Filtered
Reabsorbed
Secreted
K+
K+
Cortical portion
of collecting duct
K+
Proximal
convoluted
tubule
Excreted
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
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
Sensor
Integrating
center
Effector
Stimulus
Low Na+
intake
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
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
HCO3
Na
Proximal tubule
HCO3
ATPase
CA
H2CO3
Na
Distal tubule
H2O + CO2
Na+
H+
Blood
CA
Na
HCO3
Filtration
Lumen
+ H
Na+
H2O + CO2
H2CO3
HPO4
NH3
H2PO4
+
NH4
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+.
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.
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
Carbonic
anhydrase
inhibitors
Na+
Cortex
Amino acids
Glucose
HCO3, PO43
Thick
ascending
limb
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
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