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Chapter 17
Physiology of the Kidneys
17-1
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Chapter 17 Outline
Overview
of Kidney Structure
Nephron
Glomerular
Filtration
Function of Nephron Segments
Renal Clearance
Hormonal Effects
Na+, K+, H+, & HC03- Relationships
Clinical Aspects
17-2
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Kidney Function
Is
to regulate plasma & interstitial fluid by formation of
urine
In process of urine formation, kidneys regulate:
Volume of blood plasma, which contributes to BP
Waste products in blood
Concentration of electrolytes
Including Na+, K+, HC03-, & others
Plasma pH
17-3
Overview of Kidney Structure
17-4
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Structure of Urinary System
Paired
kidneys are
on either side of
vertebral column
below diaphragm
About size of fist
Urine flows from
kidneys into ureters
which empty into
bladder
Fig 17.1
17-5
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Structure of Kidney
 Cortex
contains many capillaries & outer parts of nephrons
 Medulla consists of renal pyramids separated by renal columns
 Pyramid contains minor calyces which unite to form a major
calyx
Fig 17.2
17-6
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Structure of Kidney continued
Fig 17.3
 Major
calyces join
to form renal pelvis
which collects urine
 Conducts urine
to ureters which
empty into
bladder
17-7
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Micturition Reflex (Urination)
 Actions
of internal & external urethral sphincters are regulated
by reflex center located in sacral part of cord
 Filling of bladder activates stretch receptors that send impulses
to micturition reflex center
 This activates Parasymp neurons causing contraction of
detrusor muscle that relaxes internal urethral sphincter
creating sense of urgency
 There is voluntary control over external urethral sphincter
 When urination is consciously initiated, descending motor tracts
to micturition center inhibit somatic motor fibers of external
urethral sphincter & urine is expelled
17-8
Nephron
17-9
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Nephron
 Is
functional unit of kidney responsible for forming urine
 >1 million nephrons/kidney
 Is a long tube & has associated blood vessels
Fig 17.2
17-10
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Renal Blood Vessels
Blood
enters kidney through renal artery
Which divides into interlobar arteries
That divide into arcuate arteries that give rise to
interlobular arteries
Fig 17.4
17-11
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Renal Blood Vessels
Interlobular
arteries give rise to afferent arterioles
which supply glomeruli
Glomeruli are mass of capillaries inside glomerular
capsule that gives rise to filtrate that enters nephron
tubule
Efferent arteriole drains glomerulus & delivers that
blood to peritubular capillaries (vasa recta)
Blood from peritubular capillaries enters veins
17-12
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Fig 17.5
17-13
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Nephron Tubules
 Tubular
part of nephron begins with glomerular capsule which
transitions into proximal convoluted tubule (PCT), then to
descending & ascending limbs of Loop of Henle (LH), & distal
convoluted tubule (DCT)
 Tubule ends where it empties into collecting duct (CD)
Fig 17.2
17-14
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Glomerular (Bowman's) Capsule
 Surrounds
glomerulus
 Together they form
renal corpuscle
 Is where glomerular
filtration occurs
 Filtrate passes into
PCT
PCT
Glomerular
capsule
Fig 17.6
17-15
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Proximal Convoluted Tubule
Walls
consist of single layer of cuboidal cells with
millions of microvilli
Which increase surface area for reabsorption
Nephron Function animation
17-16
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Type of Nephrons
 Cortical
nephrons
originate in outer 2/3
of cortex
 Juxtamedullary
nephrons originate
in inner 1/3 cortex
 Have long LHs
 Important in
producing
concentrated
urine
Fig 17.6
17-17
Glomerular Filtration
17-18
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Glomerular Filtration
Glomerular
capillaries & Bowman's capsule form a
filter for blood
Glomerular Caps are fenestrated--have large pores
between its endothelial cells
100-400 times more permeable than other Caps
Small enough to keep RBCs, platelets, & WBCs
from passing
Pores are lined with negative charges to keep
blood proteins from filtering
17-19
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Glomerular Filtration continued
 To
enter
tubule filtrate
must pass
through
narrow
filtration slits
formed
between
pedicels of
podycytes of
glomerular
capsule
Fig 17.8
17-20
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Fig 17.7
17-21
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Fig 17.9
17-22
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Glomerular Ultrafiltrate
 Is
fluid that enters
glomerular
capsule, whose
filtration was driven
by blood pressure
Fig 17.10
17-23
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Glomerular Filtration Rate (GFR)
Is
volume of filtrate produced by both kidneys/min
Averages 115 ml/min in women; 125 ml/min in men
Totals about 180L/day (45 gallons)
So most filtered water must be reabsorbed or
death would ensue from water lost through
urination
17-24
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Regulation of GFR
Is
controlled by extrinsic & intrinsic (autoregulation)
mechanisms
Vasoconstriction or dilation of afferent arterioles affects
rate of blood flow to glomeruli & thus GFR
17-25
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Sympathetic Effects
 Sympathetic
activity
constricts afferent
arteriole
 Helps maintain
BP & shunts
blood to heart &
muscles
Fig 17.11
17-26
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Renal Autoregulation
Allows
kidney to maintain a constant GFR over wide
range of BPs
Achieved via effects of locally produced chemicals on
afferent arterioles
When average BP drops to 70 mm Hg afferent
arteriole dilates
When average BP increases, afferent arterioles
constrict
17-27
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17-28
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Renal Autoregulation
 Is
also maintained by negative feedback between afferent
arteriole & volume of filtrate (tubuloglomerular feedback)
 Increased flow of filtrate sensed by macula densa (part of
juxtaglomerular apparatus) in thick ascending LH
 Signals afferent arterioles to constrict
17-29
Function of Nephron Segments
17-30
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Reabsorption of Salt & H20
In
PCT returns most molecules & H20 from filtrate back
to peritubular capillaries
About 180 L/day of ultrafiltrate produced; only 1–2 L
of urine excreted/24 hours
Urine volume varies according to needs of body
Minimum of 400 ml/day urine necessary to
excrete metabolic wastes (obligatory water loss)
17-31
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Reabsorption of Salt & H20 continued
 Return
of filtered
molecules is called
reabsorption
 Water is never
transported
 Other molecules are
transported & water
follows by osmosis
Fig 17.13
17-32
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PCT
 Filtrate
in PCT is
isosmotic to blood (300
mOsm/L)
 Thus reabsorption of H20
by osmosis cannot occur
without active transport
(AT)
 Is achieved by AT of
Na+ out of filtrate
 Loss of + charges
causes Cl- to
passively follow
Na+
 Water follows salt
by osmosis
Fig 17.14
17-33
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Insert fig. 17.14
Fig 17.15
17-34
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Significance of PCT Reabsorption
≈65%
Na+, Cl-, & H20 is reabsorbed in PCT & returned
to bloodstream
An additional 20% is reabsorbed in descending loop of
Henle
Thus 85% of filtered H20 & salt are reabsorbed early in
tubule
This is constant & independent of hydration levels
Energy cost is 6% of calories consumed at rest
The remaining 15% is reabsorbed variably,
depending on level of hydration
17-35
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Concentration Gradient in Kidney
In
order for H20 to be reabsorbed, interstitial fluid must
be hypertonic
Osmolality of medulla interstitial fluid (1200-1400
m O sm) is 4X that of cortex & plasma (300 m O sm)
This concentration gradient results largely from loop
of Henle which allows interaction between
descending & ascending limbs
17-36
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Descending Limb LH
 Is
permeable to H20
 Is impermeable to, &
does not AT, salt
 Because deep regions
of medulla are 1400
m O sm, H20 diffuses
out of filtrate until it
equilibrates with
interstitial fluid
 This H20 is
reabsorbed by
capillaries
Fig 17.17
17-37
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Ascending Limb LH
 Has
a thin segment in
depths of medulla &
thick part toward
cortex
 Impermeable to H20;
permeable to salt;
thick part ATs salt out
of filtrate
 AT of salt causes
filtrate to become
dilute (100
m O sm) by end of
LH
Fig 17.17
17-38
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Vasa Recta
Fig 17.18
 Is
important component of
countercurrent multiplier
 Permeable to salt, H20 (via
aquaporins), & urea
 Recirculates salt, trapping
some in medulla interstitial
fluid
 Reabsorbs H20 coming out
of descending limb
 Descending section has
urea transporters
 Ascending section has
fenestrated capillaries
17-42
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17-44
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Collecting Duct (CD)
Plays
important role in water conservation
Is impermeable to salt in medulla
Permeability to H20 depends on levels of ADH
17-45
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ADH
Fig 17.21
 Is
secreted by post
pituitary in response to
dehydration
 Stimulates insertion of
aquaporins (water
channels) into plasma
membrane of CD
 When ADH is high, H20
is drawn out of CD by
high osmolality of
interstitial fluid
 & reabsorbed by vasa
recta
17-46
Renal Clearance
17-48
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Renal Clearance
 Refers
to ability of kidney to remove substances from blood &
excrete them in urine
 Occurs by filtration & by secretion
 Secretion is opposite of reabsorption--substances from vasa
recta are transported into tubule & excreted
 Reabsorption decreases renal clearance; secretion increases
clearance
Fig 17.22
17-49
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Secretion of Drugs
Many
drugs, toxins, & metabolites are secreted by
organic anion transporters of the PCT
Involved in determining half-life of many therapeutic
drugs
17-50
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Measurement of Renal Blood Flow
Not
all blood delivered to glomerulus is filtered into
glomerular capsule
20% is filtered; rest passes into efferent arteriole &
back into circulation
Substances that aren't filtered can still be cleared by
active transport (secretion) into tubules
17-55
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Glucose & Amino Acid Reabsorption
Filtered
glucose & amino acids are normally 100%
reabsorbed from filtrate
Occurs in PCT by carrier-mediated cotransport with
Na+
Transporter displays saturation if ligand
concentration in filtrate is too high
 Level needed to saturate carriers & achieve
maximum transport rate is transport maximum
(Tm)
Glucose & amino acid transporters don't saturate
under normal conditions
17-58
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Glycosuria
Is
presence of glucose in urine
Occurs when glucose > 180-200mg/100ml plasma
(= renal plasma threshold)
Glucose is normally absent because plasma levels
stay below this value
Hyperglycemia has to exceed renal plasma
threshold
Diabetes mellitus occurs when hyperglycemia
results in glycosuria
17-59
Hormonal Effects
17-60
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Electrolyte Balance
regulate levels of Na+, K+, H+, HC03-, Cl-, &
PO4-3 by matching excretion to ingestion
Control of plasma Na+ is important in regulation of
blood volume & pressure
Control of plasma of K+ important in proper function of
cardiac & skeletal muscles
Kidneys
17-61
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Role of Aldosterone in Na+/K+ Balance
filtered Na+ & K+ reabsorbed before DCT
Remaining is variably reabsorbed in DCT & cortical
CD according to bodily needs
Regulated by aldosterone (controls K+ secretion
& Na+ reabsorption)
In the absence of aldosterone, 80% of remaining
Na+ is reabsorbed in DCT & cortical CD
When aldosterone is high all remaining Na+ is
reabsorbed
90%
17-62
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Renin-Angiotensin-Aldosterone System
Is
activated by release of renin from granular cells
within afferent arteriole
Renin converts angiotensinogen to angiotensin I
Which is converted to Angio II by angiotensinconverting enzyme (ACE) in lungs
Angio II stimulates release of aldosterone
17-65
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Regulation of Renin Secretion
Inadequate
intake of NaCl always causes decreased
blood volume
Because lower osmolality inhibits ADH, causing less
H2O reabsorption
Low blood volume & renal blood flow stimulate renin
release
Via direct effects of BP on granular cells & by
Symp activity initiated by arterial baroreceptor
reflex (see Fig 14.26)
17-66
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Macula Densa
 Is
region of
ascending limb in
contact with afferent
arteriole
 Cells respond to
levels of Na+ in
filtrate
 Inhibit renin
secretion when
Na+ levels are
high
 Causing less
aldosterone
secretion, more
Na+ excretion
Fig 17.26
17-68
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17-69
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Atrial Natriuretic Peptide (ANP)
Is
produced by atria due to stretching of walls
Acts opposite to aldosterone
Stimulates salt & H20 excretion
Acts as an endogenous diuretic
17-70
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Renal Acid-Base Regulation
help regulate blood pH by excreting H+ &/or
reabsorbing HC03Most H+ secretion occurs across walls of PCT in
exchange for Na+ (Na+/H+ antiporter)
Normal urine is slightly acidic (pH = 5-7) because
kidneys reabsorb almost all HC03- & excrete H+
Kidneys
17-73
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Urinary Buffers
Nephron
cannot produce urine with pH < 4.5
Excretes more H+ by buffering H+s with HPO4-2 or NH3
before excretion
Phosphate enters tubule during filtration
Ammonia produced in tubule by deaminating amino
acids
Buffering reactions
 HPO4-2 + H+  H2PO4 NH3 + H+  NH4+ (ammonium ion)
17-76
Clinical Aspects
17-77
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Diuretics
 Are
used to lower blood volume because of hypertension,
congestive heart failure, or edema
 Increase volume of urine by increasing proportion of glomerular
filtrate that is excreted
 Loop diuretics are most powerful; inhibit AT salt in thick
ascending limb of LH
 Thiazide diuretics inhibit NaCl reabsorption in 1st part of DCT
 Carbonic anhydrase inhibitors prevent H20 reabsorption in PCT
when HC0s- is reabsorbed
 Osmotic diuretics increase osmotic pressure of filtrate
17-78
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Kidney Diseases
In
acute renal failure, ability of kidneys to excrete
wastes & regulate blood volume, pH, & electrolytes is
impaired
Rise in blood creatinine & decrease in renal plasma
clearance of creatinine
Can result from atherosclerosis, inflammation of
tubules, kidney ischemia, or overuse of NSAIDs
17-80
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Kidney Diseases continued
Glomerulonephritis
is inflammation of glomeruli
Autoimmune attack against glomerular capillary
basement membranes
Causes leakage of protein into urine resulting in
decreased colloid osmotic pressure & resulting
edema
17-81
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Kidney Diseases continued
 In
renal insufficiency, nephrons have been destroyed as a result
of a disease
 Clinical manifestations include salt & H20 retention & uremia
(high plasma urea levels)
 Uremia is accompanied by high plasma H+ & K+ which
can cause uremic coma
 Treatment includes hemodialysis
 Patient's blood is passed through a dialysis machine
which separates molecules on basis of ability to diffuse
through selectively permeable membrane
 Urea & other wastes are removed
17-82