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Chapter 17
Physiologyof the
Kidneys
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I. Structure and Function ofthe Kid neys
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A. Kidney Functions
1. Regulation of the extracellular fluid environment inthe body, including:
a. Volume of blood plasma (affects blood pressure)b. Wastesc. Electrolytesd. pH
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B. Gross structure of the urinary system
1. Introductiona. 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 p eristalsis.
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Organs of the urinary system
Renal arteryRenal vein
Inferior vena cava
Kidney
Renal vein
Renal artery
Abdominalaorta
Ureter
Urinarybladder
Urethra
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2. Kidney Structure
a. The kidney has two distinct regions:1) Renal cortex2) Renal medulla, made up of renal pyramids and
columns
b. Each pyramid drains into a minor calyx major
calyx renal pelvis.
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Radiograph of the urinary systemCopyright The McGraw-Hill Companies, Inc. Permission required for reproduction or di splay.
Twelfththoracicvertebra
Twelfthrib
Minor
calyx
Renalpelvis
Kidney
Ureter
Urinary
bladder SPL/Photo Researchers
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Control of Micturition, cont
3. Stretch receptors in the bladder send informationto S2S4 regions of the spinal cord.
a. These neurons normally inhibit parasympatheticnerves to the detrusor muscles, while somaticmotor neurons to the external urethral sphincterare stimulated.
b. Called the guarding reflex
c. Prevents involuntary emptying of bladder
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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 detrusormuscles to contract rhyt hmicallyc. 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.
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D. Microscopic Kidney Structure
1. Nephron: functional unit of the kidneya. Each kidney has more than a million nephrons.b. Nephron consists of small tubules and
associated blood vessels.c. Blood is filtered, fluid e nters the tubules, is
modified, then leaves t he tubules as urine
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Renal cortex
Renal medulla
Renal pyramid
Renal column
Renal pelvis
Renal papilla
(a)
Distalconvolutedtubule
Collectingduct
(c)
Minor calyx
Major calyx
Renalcortex
Renalartery
Renalvein
Ureter
Renalmedulla
Renalpapilla
Minor calyx
Glomerular capsule
Proximalconvolutedtubule
Loop of Henle
Nephron
(b)
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Kidney Structure
I
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2. Renal Blood Vessels
Renal arteryInterlobar arteries
Arcuate arteriesInterlobular arteries
Afferent arteriolesGlomerulusEfferent arteriolesPeritubular capillaries
Interlobular veins Arcuate veinsInterlobar veinsRenal vein
Interlobular arteryand veinRenal cor tex
Arcuate arteryand vein
Interlobar arteryand vein
Renal med ullaRenal arter y
Renal pelvi s
Renal vein
Ureter
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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Nephron Tubules & Associated Blood Vessels
Glomerulus
Glomerular capsule
Efferent arteriole
Aff erent art erio le
Interlobular artery
Proximalconvolutedtubule
Arc uate art eryand vein
Interlobar artery and vein
Nephron lo op(of Henle) Ascending
limb
Descendinglimb
Collectingduct
Interlobula r vein
Peritubular capillaries(vasa recta)
Distal convoluted tubulePeritubular capillaries
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4. Two Types of Nephrons
a. Juxtamedullary: better at making concentratedurine
b. CorticalCopyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Renal cortex
Renal medulla
Collecting duct
(b)
Bloodflow
Glomerulus
(a)
Juxtamedullarynephron
Corticalnephron
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II. Glomerular Filtration
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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 glomeru lar capsule is calledfiltrate
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Glomerular Corpuscle, cont
3. Filtrates must pass through:a. Capillary fenestraeb. Glomerular basement membrane
c. Visceral layer of the glomerular capsulecomposed of cells called podocytes withextensions called pedicl es
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Glomerular Capillaries & Capsule
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Podocytecell body
Primaryprocess o f podocyte
Branchingpedicels
Professor P.M. Motta and M. Sastell ucci/SPL/Photo Researchers
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Glomerular Corpuscle & Filtration Barrier
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Proximal convoluted tubule
Glomerular (Bowmans) capsule
Podocyte of vis ceral layer of glomerular capsule
Pedicel(footprocess)
Fenestrae
Filtrationslits
Podocyte foot process
Slit diaphragm
Glomerular basementmembrane
Capillary endothelium
Fenestrae
Parietal layer of glomerular capsule
Efferentarteriole
Bloodflow
Aff eren tarteriole
Glomerulus
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Footprocesses
FiltrateSlit diaphragm
Basement membrane
FenestraPlasma
Capillary lumen
Erythrocyte
Donald Fawcett & D. F riend/Visuals Unlimited, Inc
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Glomerular Corpuscle, cont
d. Slits in the pedicles called slit diaphragm pores arethe major barrier for the filtration of plasmaproteins.
1) Defect here causes proteinuria = proteins inurine.
2) Some albumin is filtered out but is reabsorbe dby active endocytosis.
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B. Glomerular Ultrafiltrate
1. Fluid in glomerular capsule gets there viahydrostatic pressure of the blood, colloid osmoticpressure, and very permeable capillaries.
2. These forces produce a net filtration pressure ofabout 10mmHg
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Formation of Glomerular Ultrafiltrate
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Glomerular (Bowmans)capsule
Glomerular ultrafiltrate
Efferentarteriole
Other solutes
Protein Afferentarteriole
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3. Filtration Rates
a. Glomerular filtration rate (GFR): volume of filtrateproduced by both kidneys each minute = 115125ml.
1) 180 L/day (~45 gal)2) Total blood volume is fil tered every 40 minute s3) Most must be reabsorbe d immediately
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C. Regulation of Glomerular Filtration Rate
1. Vasoconstriction or dilation of afferent arterioleschanges filtration rate.
a. Extrinsic regulation via sympathetic nervoussystem
b. Intrinsic regulation via si gnals from the kidne ys;called renal autoregulati on
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2. Sympathetic Nerve Effects
a. In a fight/flight reaction, there is vasoconstriction ofthe afferent arterioles.
b. Helps divert blood to heart and muscles
c. Urine formation decreases to compensate for thedrop in blood pressure
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Sympathetic Nerve EffectsCopyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Exercise
Stimuli
Blood pressure
Baroreceptor reflex
Sympatheticnerve activity
Vasoconstrictionin ski n, GI tract
Negative feedback corrections
Blood volume
Urineproduction
GFR
Totalperipheralresistance
Cardiacoutput
Vasoconstrictio nof afferent arterioles
in kidneys
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3. Renal Autoregulation
a. GFR is maintained at a constant level even whenblood pressure (BP) fluctuates greatly.
1) Afferent arterioles dilate if BP < 70.
2) Afferent arterioles constrict if BP > normal.b. Myogenic constriction: Sm ooth muscles inarterioles sense an increa se in blood pressure.
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Renal Autoregulation, cont
c. Tubuloglomerular feedback: Cells in theascending limb of the loop of Henle calledmacula densa sense a rise in water andsodium as occurs with increased bloodpressure (and filtration rate).
1) They send a chemical signal (ATP) toconstrict the afferent arterioles.
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Regulation of Glomerular Filtration Rate
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III. Reabsorption of Salt and
Water
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A. Introduction
1. Reabsorption return of filtered molecules to theblood
2. 180 L of water is filtered per day, but only 12 L isexcreted as urine.
a. This will increase when well hydrated anddecrease when dehydra ted.
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. Thisportion is unregulated.
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Filtration and ReabsorptionCopyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
FiltrationReabsorption
GlomerulusGlomerular (Bowmans) capsule
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B. Reabsorption in the Proximal Tubule
1. The osmolality of filtrate in the glomerular capsuleis equal to that of blood plasma (isoosmotic).
2. Na+
is actively transported out of the filtrate intothe peritubular blood to se t up a concentrationgradient to drive osmosis.
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3. Active Transport
a. Cells of the proximal tubules are joined by tight junctions on the apical side (facing inside thetubule).
b. The apical side also contains microvilli.c. These cells have a lower N a + concentration tha n
the filtrate inside the tubul e due to Na +/K+ pump son the basal side of the cells and low permeability
to Na+.
d. Na + from the filtrate diffuses into these cells and isthen pumped out the other side.
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4. Passive Transport
a. The pumping of sodium into the interstitial spaceattracts 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 diffus es into the peritubular
capillaries.
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Salt and Water Reabsorption in the Proximal Tubule
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or di splay.
Glomerular (Bowmans)
capsule
FiltrationReabsorption
Cl
transport(passive)
Na +
transport(active)
H2O followssalt byosmosis
Fluid reduced to1/3 original volume,
but still isosmotic
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5. Significance of proximal tubule reabsorption
a. 65% of the salt and water is reabsorbed, but that isstill too much filtrate
b. An additional 20% of water is reabsorbed throughthe descending limb of the Loop of Henle.
1) Happens continuously a nd is unregulated2) The final 15% of water ( ~27 L) is absorbed la ter
in the nephron under hormonal control.
3) Fluid entering loop of Henle is isotonic toextracellular fluids.
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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 theosmosis of water.b. The ascending portion s ets up this gradient.
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2. Ascending Limb of the Loop of Henle
a. Salt (NaCl) is actively pumped into the interstitialfluid from the thick segment of the limb
1) Movement of Na + down its electrochemicalgradient from filtrate into tubule cells powers thesecondary active transport of Cl and K +.
2) Na + is moved into inters titial space via Na +/K+
pump. Cl follows Na + passively due to electrical
attraction, and K+
passively diffuses back intofiltrate.
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Transport of Ions in the Ascending Limb of theLoop of Henle
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or di splay.
1
3
2
K+
Interstitialspace
Filtrate(tubular lumen)
Apicalmembrane
2 Cl
Na +
K+
K+
Na +
Ascending limb of loop
Na + Na +
ADP
ATP
K+ K+
K+
K+
Cl
Cl
Cl
Cl
Basolateralmembrane
2 Cl
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Ascending Limb of the Loop of Henle, cont
b. Walls are not permeable to water, so osmosiscannot occur from the ascending part of the loop.
c. Surrounding interstitial fluid becomes increasinglysolute concentrated at the bottom of the tube.
d. Tubular fluid entering the d escending loop ofHenle becomes more hyp otonic as it descends theloop.
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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 bycapillaries.
c. As it descends, the fluid b ecomes more soluteconcentrated.
1) This is perfect for salt transport out of the fluid in
the ascending portion.
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Countercurrent Multiplier System
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or di splay.
2
1
3
6 0 0
8 0 0
1 , 0 0
0 1
, 0 0 0
8 0 0
6 0 0
4 0 0
1,400
Cortex
Medulla
Capillary
300mOsm Loop of Henle
Na +Cl
Na +Cl
Na +Cl
Na +Cl
Na +Cl
Na +Cl
Na +Cl
Na +Cl
H2O
H2O
H2O
Ascend ing li mb
Act ive t ranspor t of Na +,
Cl
follows passively;impermeable to water
Descending limb
Passively permeable
to water
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4. Countercurrent Multiplication
a. Positive feedback mechanism is created betweenthe two portions of the loop of Henle.
1) The more salt the ascending limb removes, thesaltier the fluid entering it will be (due to loss ofwater in descending limb).
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b. Steps of countercurrent mechanism
1) Interstitial fluid is hypertonic due to NaCl pumpedout of the ascending limb
2) Water leaves descending limb by osmosis, makingthe filtrate hypertonic going into the ascending limb
3) More NaCl in the ascendin g limb can now bepumped out into the inters titial fluid
4) The greater concentration of the interstitial fluid
draws more water from the descending limb5) Filtrate in ascending limb now more concentrated6) Continues until the maximum NaCl concentration
of the inner medulla is reached.
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Vasa Recta, cont
3) High salt concentration (oncotic pressure) at thebeginning of the ascending region pulls in water,which is removed from the interstitial space.
a) Also keeps salt concentration in the interstitialspace high
4) There are also urea transp orters and aquaporin sto aid in the countercurrent exchanges
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5. Effects of Urea
a. Urea is a waste product of protein metabolismb. Contributes to countercurrent system
1) Transported out of collecting duct and intointerstitial fluid
2) Diffuses back into ascen ding limb and cycles around continuously
3) Helps set up solute concentration gradients
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Role of Urea in Urine ConcentrationCopyright The McGraw-Hill Companies, Inc. Permission required for reproduction or d isplay.
2
1
3
H2O
Collectingduct
H2O
H2O
Cortex
Outer medulla
NaCl
Urea
Water Loop of Henle
H2O
H2O
H2OH2O
Inner medulla
Distal tubule
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Renal Tubule Transport Properties
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Renal Tubule OsmolalityCopyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Proximal
tubule
300
Distal
tubule
Collectingduct
Cortex
Outer medulla
Inner medullaH2O
H2O
800
1,200
1,400 H2O1,400
800800
1,200
1,400
1,200
Ascen din glimb of loop
Descendinglimb of loop
Vasa recta
800
600
800
400
400
400
200
100
300
400
600 600
400
320
300
100
H2O
H2O
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D. Collecting Duct and ADH
1. Last stop in urine formation2. Impermeable to NaCl but permeable to water
a. Also influenced by hypertonicity of interstitialspace water will leave via osmosis if able to
b. Permeability to water de pends on the numbe r ofaquaporin channels in t he cells of the collecti ngduct
c. Availability of aquaporins determined by ADH(antidiuretic hormone)
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Collecting Duct and ADH, cont
3. ADH binds to receptors on collecting duct cellscAMP Protein kinase Vesicles withaquaporin channels fuse to plasma membrane.
a) Water channels are removed without ADH.4. ADH is produced by neur ons in the hypothalam us
but stored and released fr om the posteriorpituitary gland
a) Release stimulated by an increase in bloodosmolality
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Homeostasis of Plasma Concentration by ADHCopyright The McGraw-Hill Companies, Inc. Permission required for reproduction or di splay.
StimulusStimulus
Negative
feedbackcorrection
Negative
feedbackcorrection
ADH ADH
Sensor
Integrating center Effector
Water reabsorption
More water excreted in urine
Less water excreted in urine
Water reabsorption
Kidneys
Posterior pituit ary
Osmoreceptors in
hypothalamus
Plasmaosmolality
Plasmaosmolality
High water intake(over-hydration)
Low w ater intake(dehydration)
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ADH Secretion and Action
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IV. Renal Plasma Clearance
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A. Transport processes affecting renal clearance
1. Kidneys must also remove excess ions and wastesfrom the blood.a. Sometimes called renal clearanceb. Filtration in the glomerular capsule begins this
process.c. Reabsorption returns so me substances to th e
blood (decreases renal clearance)
d. Secretion finishes the process when substancesare moved from the peritubular capillaries intothe tubules. (increases renal clearance)
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2. Excretion Rate
a. Excretion rate = (filtration rate + secretion rate) reabsorption rateb. Used to measure glomerular filtration rate
(GFR), an indicator of renal health
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Secretion is the reverse of reabsorption
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
FiltrationReabsorptionSecretion
Excretion
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3. Secretion of Drugs
a. Membrane carriers specific to foreign substancestransport them into the tubules.b. Called organic anion transporters (OATs) or
organic cation transporters (OCTs)c. Carriers are polyspecific overlap in functiond. Very fast; may interfere wi th action of therapeut ic
drugs
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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 orsecreted
V X UGFR = ----------
P
V = rate of urine formationU = inulin concentration in urineP = inulin concentration in plasma
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2. Renal Plasma Clearance Calculation
a. Volume of plasma from which a substance iscompletely removed by the kidneys in 1 minute1) Inulin is filtered only. Clearance = GFR2) 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 asGFR.
b. Clearance of urea is less than GFR means someis reabsorbed
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Renal Plasma Clearance
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C. Clearance of PAH
1. Not all blood delivered to the glomeruli is filtered in eachpass, so blood must make several passes to completelyclear a substance.
2. PAH (para-aminohippuric acid) is an exogenous moleculeinjected for measurement of total renal blood flow.
3. Substances not filtered must be secreted into the tubulesby active transport from the pe ritubular capillaries
4. All PAH in the peritubular capillaries will be secreted byOATs, so the time it takes to clear all PAH injected
indicates blood flow to these capillaries.
l l f
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Renal Clearance of PAHCopyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
PAH
Filtration
To peritubular capillaries
Renal arterycontaining PAH
Renal veinalmost no PAH
Ureter urine containing almostall PAH that w as in
renal artery
Filtration plussecretion
(d)To r enal vein
Peritubular capillaries
(a)
(c)
f
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D. Reabsorption of Glucose
1. Glucose (and amino acids) is easily filtered out intothe glomerular capsule2. Completely reabsorbed in the proximal tubule via
secondary active transport with sodium, facilitateddiffusion, and simple diffusion
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Mechanism of Reabsorption in the proximal tubuleCopyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
K+
K+
1
2
3
Lumen of kidney tubule
Api cal
membraneGlucose
Na +
Cotransport
Basolateralmembrane
Facilitateddiffusion
Proximaltubule cell
Primary activetransport
Glucose
Na +
Capillary
ATP ADP
Simplediffusion
R b i f Gl
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Reabsorption of Glucose, cont
3. Glucose/Na + cotransporters have a transportmaximum (T m).
a. If there is too much glucose in the filtrate, it will
not be completely reabsorbed because all thecarriers are in use (satu rated).b. Extra glucose spills ove r into the urine =
glycosuria and is a sign of diabetes mellitus.
c. Extra glucose in the blood also results indecreased water reabsorption and possibledehydration.
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V. Renal Control of Electrolyte
and Acid-Base Balance
A I d i
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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 im portant in healthy
skeletal and cardiac muscle activity.c. Aldosterone plays a big role in Na + and K +
balance.
B R l f Ald t i N +/K+ B l
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B. Role of Aldosterone in Na +/K+ Balance
1. About 90% of filtered Na + and K + is reabsorbedearly in the nephron.
a. This is not regulated.
2. An assessment of what th e body needs is mad e,and aldosterone controls additional reabsorption ofNa + and secretion of K + in the distal tubule andcollecting duct.
3 P t i S ti
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3. Potassium Secretion
a. Aldosterone independent response: Increase inblood 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 re sponse: Increase in
blood K + triggers adrenal cortex to release
aldosterone.1) This increases K + secretion in the distal tubuleand collecting duct.
P t i i R b b d d S t d
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Potassium is Reabsorbed and Secreted
Filtered Reabsorbed
Secreted
Cortical portionof collecting duct
ExcretedProximalconvolutedtubule
K+
K+
K+
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or di splay.
S di d P t i
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c. Sodium and Potassium
1) Increases in sodium absorption drive extrapotassium secretion.2) Due to:
a) Potential difference created by Na + reabsorptiondriving K + through K + ch annels
b) Stimulation of renin-ang iotensin-aldosteronesystem by water and Na + in filtrate
c) Increased flow rates bend cilia on the cells ofthe distal tubule, resulting in activation of K +
channels
4 Control of Aldosterone Secretion
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4. Control of Aldosterone Secretion
a. A rise in blood K + directly stimulates production ofaldosterone in the adrenal cortex.
b. A fall in blood Na + indirectly stimulates production
of aldosterone via the renin- angiotensin-aldosterone system.
C Juxtaglomerular Apparatus
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C. Juxtaglomerular Apparatus
1. Located where the afferent arteriole comes intocontact with the distal tubuleCopyright The McGraw-Hill Companies, Inc. Permission required for reproduction or di splay.
Aff eren tarteriole
Juxtaglomerular apparatusMacula
densa
Granular cells
Thickascending limb
(a)
Loop of Henle
(b)
Glomerulus
Glomerular capsule
Region of the juxt agl omeru lar
apparatus
Aff eren tarteriole
Glomerulus
Efferentarteriole
Distaltubule
Efferentarteriole
Juxtaglomerular Apparatus cont
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Juxtaglomerular Apparatus, cont
2. A decrease in plasma Na+
results in a fall inblood volume.a. Sensed by juxtaglomerular apparatusb. Granular cells secrete renin into the afferent
arteriole.c. This converts angioten sinogen into
angiotensin I.
d. Angiotensin-converting enzyme (ACE)converts this into angiotensin II.
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4 Regulation of Renin Secretion
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4. Regulation of Renin Secretion
a. Low salt levels result in lower blood volume due toinhibition 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 barorecep tors. They then secr eterenin.
1) Granular cells are also stimulated bysympathetic innervation from the baroreceptorreflex.
Homeostasis of Plasma Na +
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Homeostasis of Plasma NaCopyright The McGraw-Hill Companies, Inc. Permission required for reproduction or di splay.
Juxtaglomerular apparatus
Renin
Ang io tensin II
Adrenal co rt ex
Aldos terone
Na + reabsorption incortical collecting duct
Low plasmaNa + concentration
Hypothalamus
Posterior pituitary
ADH
Water reabsorptionin collecting ducts
Urine volume
Sympatheticnerve activity
Blood volume
Negative feedback correctionStimulusSensor
Integratingcenter Effector
Low Na +intake
Na + retentionin blood
5 Macula Densa
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5. Macula Densa
a. Part of the distal tubule that forms the juxtaglomerular apparatusb. Sensor for tubuloglomerular feedback needed for
regulation of glomerular filtration rate1) When there is more Na + and H 2O in the filtrat e,
a signal is sent to the af ferent arteriole toconstrict limiting filtration rate.
2) Controlled via negative feedback
Macula Densa cont
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Macula Densa, cont
c. When there is more Na + and H 2O in the filtrate, asignal is sent to the afferent arteriole to inhibit theproduction of renin.
1) This results in less reabsorption of Na+
, allowingmore to be excreted.2) This helps lower Na + levels in the blood.
D Atrial Natriuretic Peptide
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D. Atrial Natriuretic Peptide
1. Increases in blood volume also increase therelease of atrial natriuretic peptide hormone fromthe atria of the heart when atrial walls arestretched.
2. Stimulates kidneys to excrete more salt andtherefore more water
3. Decreases blood volume and blood pressure
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Reabsorption of Na + and Secretion of K + and H +
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Reabsorption of Na and Secretion of K , and H
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or di splay.
K+ or H +
Peritubular capillariesBlood
Na +
Na + Na +
Na +
Na +
Na +
Na + Na +
K+
Na +
H+Na +
K+
K+Na +
K+H+
Na +
Ascending limbof Henles loop
Medullarycollectingduct
Distal tubuleCortical collectin g duct
K+/H+
F Acid-Base Regulation
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F. Acid Base Regulation
1. Kidneys maintain blood pH by reabsorbingbicarbonate 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
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Acid Base Regulation, cont
3. Bicarbonate cannot cross the inner tubulemembrane so must be converted to CO 2 and H 2Ousing carbonic anhydrase.
a. Bicarbonate + H + carbonic acidb. Carbonic acid (w/ carbo nic anhydrase)
H2O + CO 2c. CO 2 can cross into tubule cells, where the
reaction reverses and bicarbonate is madeagain.
d. This diffuses into the interstitial space.
Acidification of the Urine
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Acidification of the Urine
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
H+
+
+ H+
H++
K+
Blood
Proximal tubule cell
Lumen
Distal tubule
Proximal tubule
CA
HCO 3
HCO 3
Na +
Na +
HCO 3 H+
H+
CA
H2CO 3
H2O CO 2
H2OH2CO 3 CO 2 Na +
Na +
NH4+
NH3
H2PO 4 HPO 4
2
ATPase
Na +
Filtration
Acid-Base Regulation cont
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Acid Base Regulation, cont
4. Aside from the Na +/H+ pumps in the proximaltubule, the distal tubule has H + ATPase pumps toincrease H + secretion.
5. pH Disturbances
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5. pH Disturbances
a. Kidneys can help compensate for respiratoryproblemsb. Alkalosis: Less H + is available to transport
bicarbonate into tubule cells, so less bicarbonate isreabsorbed; extra bicarbo nate secretioncompensates for alkalosis.
pH Disturbances, cont
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pH Disturbances, cont
c. Acidosis: Proximal tubule can make extrabicarbonate through the metabolism of the aminoacid glutamine.
1) Extra bicarbonate enters the blood tocompensate for acidosis .2) Ammonia stays in urine to buffer H +.
Disturbances of Acid-Base Balance
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Disturbances of Acid Base Balance
G. Urinary Buffers
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G. Urinary Buffers
1. Nephrons cannot produce urine with a pHbelow 4.5.
2. To increase H + secretion, urine must be
buffered.a. Phosphates and amm onia buffer the urine.b. Phosphates enter via filtration.
c. Ammonia comes from the deamination ofamino acids.
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A. Use of Diuretics
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1. Used clinically to control blood pressure andrelieve edema (fluid accumulation)
a. Diuretics increase urine volume, decreasing
blood volume and interstitial fluid volume.b. Many types act on differ ent portions of the
nephron.
2. Types of Diuretics
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yp
a. Loop diuretics: most powerful; inhibit salt transportout of ascending loop of Henle
1) Example: Lasix2) Can inhibit up to 25% of water reabsorption
b. Thiazide diuretics: inhibit s alt transport in distaltubule
1) Can inhibit up to 8% of water reabsorption
c. Carbonic anhydrase inhibitors: much weaker;inhibit water reabsorption when bicarbonate isreabsorbed
1) Also promote excretion of bicarbonate
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Sites of Action of Clinical Diuretics
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Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
K+
Carbonicanhydraseinhibitors
Thiazidediuretics
Distal convoluted tubuleProximal convoluted tubule
Cortex
Medulla
Passive
Glomerulus
Passive
NaCl
Thick
ascendinglimb
H2O
Corticalcollectingduct
Collectingduct
Medullarycollectingduct
UreaNaCl
H2O
H2O
Na +
Loopdiuretics
Na +
H2O
(with ADH)
H2Ono
ADH
Asc endinglimb
Descendinglimb
Ami no acidsGlucose
H2Ono
ADH
(with ADH)
Potassium-sparing
diuretics
HCO 3 , PO 4
3
IncreasingNaCl and ureaconcentrations
B. Renal Function Tests
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1. PAH and inulin clearancea. Can diagnose nephritis or renal insufficiency2. Urinary albumin excretion rate: detects above-
normal albumin excretiona. Called microalbuminuriab. Signifies renal damage due to hypertension o r
diabetes
3. Proteinuria: overexcretion of proteins; signifiesnephrotic syndrome
C. Kidney Diseases
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y
1. Acute Renal Failurea. Ability of kidneys to regulate blood volume, pH,
and solute concentrations deteriorates in amatter of hours/days.
b. Usually due to decrease d blood flow through kidneys due to:1) Atherosclerosis of renal arteries
2) Inflammation of renal tubules3) Use of certain drugs (NSAIDs)
2. Glomerulonephritis
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p
a. Inflammation of the glomerulusb. Autoimmune disease with antibodies produced inresponse to streptococcus infection
c. Many glomeruli are destroyed, and others aremore permeable to protein s.
d. Loss of proteins from bloo d reduces blood osm oticpressure and leads to edema.
3. Renal Insufficiency
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a. Any reduction in renal activityb. 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 = ure a in the blood.
d. Patients with uremia are placed on a dialysismachine to clear blood of these solutes.
4. Dialysis
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a. Artificial kidneyb. Hemodialysis blood cleansed of wastes as itpasses through dialysis fluid
c. CAPD continuous ambulatory peritoneal dialysis dialysis fluid introduced t o the abdominal cavi tywhere wastes can pass ou t of abdominal blood vessels; fluid is then pumped out of the abdominalcavity
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8/10/2019 Chapter 17 kidneys physio
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THANK Y OU !!!
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