Chapter 17 kidneys physio

8/10/2019 Chapter 17 kidneys physio

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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)


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



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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


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


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


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


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


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


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


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+


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


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


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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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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y

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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THANK Y OU !!!

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Chapter 17 kidneys physio