physiology of the renal system

7/21/2019 Physiology of The Renal System

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Physiology of kidneysPhysiology of kidneys


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The Nephron Is the Functional UnitThe Nephron Is the Functional Unit

of the Kidneyof the Kidney Each kidney in theEach kidney in the

human contains abouthuman contains about1 million nephrons,1 million nephrons,each capable ofeach capable offorming urine. Theforming urine. Thekidney cannotkidney cannotregenerate newregenerate newnephrons. Therefore,nephrons. Therefore,with renal injury,with renal injury,disease, or normaldisease, or normal

aging, there is aaging, there is agradual decrease ingradual decrease innephron number.nephron number.


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Each nephronEach nephroncontains (1) a tuftcontains (1) a tuftof glomerularof glomerular

capillaries calledcapillaries calledthe glomerulus,the glomerulus,through whichthrough whichlarge amounts oflarge amounts offluid are filteredfluid are filteredfrom the blood,from the blood,and (2) a longand (2) a longtubule in whichtubule in whichthe filtered fluidthe filtered fluidis conerted intois conerted intourine on its wayurine on its way

to the pelis ofto the pelis ofthe kidney.the kidney.


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The macula densa plays an important role in controllingThe macula densa plays an important role in controllingnephron function. !eyond the macula densa, fluid entersnephron function. !eyond the macula densa, fluid entersthe distal tubule that, like the pro"imal tubule, lies in thethe distal tubule that, like the pro"imal tubule, lies in the

renal corte".renal corte".


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Renal Blood SupplyRenal Blood Supply

!lood flow to the two kidneys is normally about 22 per cent of!lood flow to the two kidneys is normally about 22 per cent ofthe cardiac output, or 11## ml$min.the cardiac output, or 11## ml$min.

The renal artery enters the kidney through the hilum and thenThe renal artery enters the kidney through the hilum and thenbranches progressiely to form the interlobar arteries, arcuatebranches progressiely to form the interlobar arteries, arcuate

arteries, interlobular arteries (also called radial arteries), andarteries, interlobular arteries (also called radial arteries), andafferent arterioles, which lead to the glomerular capillaries,afferent arterioles, which lead to the glomerular capillaries,where large amounts of fluid and solutes (e"cept the plasmawhere large amounts of fluid and solutes (e"cept the plasma

proteins) are filtered to begin urine formation.proteins) are filtered to begin urine formation. The distal ends of the capillaries of each glomerulus coalesceThe distal ends of the capillaries of each glomerulus coalesce

to form the efferent arteriole, which leads to a second capillaryto form the efferent arteriole, which leads to a second capillarynetwork. the peritubular capillaries, that surrounds the renalnetwork. the peritubular capillaries, that surrounds the renaltubules.tubules.

%ideo%ideo
http://217.196.164.19/data/teacher/video/fiz_pat/Video1/F199975_kidney.movhttp://217.196.164.19/data/teacher/video/fiz_pat/Video1/F199975_kidney.movhttp://217.196.164.19/data/teacher/video/fiz_pat/Video1/F199975_kidney.mov


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PHYSI!"I# #NTR! F "!$%RU!&RPHYSI!"I# #NTR! F "!$%RU!&R

FI!TR&TIN &N' R%N&! B!' F!(FI!TR&TIN &N' R%N&! B!' F!(

The determinants of &' thatThe determinants of &' thatare most ariable and subject toare most ariable and subject to

physiologic control include thephysiologic control include theglomerular hydrostatic pressureglomerular hydrostatic pressureand the glomerular capillaryand the glomerular capillarycolloid osmotic pressure.colloid osmotic pressure.

These ariables, in turn, areThese ariables, in turn, areinfluenced by the sympatheticinfluenced by the sympatheticnerous system, hormones andnerous system, hormones andautacoids (asoactie substancesautacoids (asoactie substances

that are released in the kidneysthat are released in the kidneysand act locally), and otherand act locally), and otherfeedback controls that arefeedback controls that areintrinsic to the kidneys.intrinsic to the kidneys.


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Sy)pathetic Ner*ous Syste)Sy)pathetic Ner*ous Syste)

&cti*ation 'ecreases "FR&cti*ation 'ecreases "FR trong actiation of the renal sympathetic neres can constrict the renaltrong actiation of the renal sympathetic neres can constrict the renal

arterioles and decrease renal blood flow and &'.arterioles and decrease renal blood flow and &'. *oderate or mild sympathetic stimulation has little influence on renal*oderate or mild sympathetic stimulation has little influence on renal

blood flow and &'. 'or e"ample, refle" actiation of the sympatheticblood flow and &'. 'or e"ample, refle" actiation of the sympatheticnerous system resulting from moderate decreases in pressure at the carotidnerous system resulting from moderate decreases in pressure at the carotid

sinus baroreceptors or cardiopulmonary receptors has little influence onsinus baroreceptors or cardiopulmonary receptors has little influence onrenal blood flow or &'. *oreoer, because the baroreceptors adaptrenal blood flow or &'. *oreoer, because the baroreceptors adaptwithin minutes or hours to sustained changes in arterial pressure, il iswithin minutes or hours to sustained changes in arterial pressure, il isunlikely that these refle" mechanisms hae an important role in longtermunlikely that these refle" mechanisms hae an important role in longtermcontrol of renal blood flow and &'.control of renal blood flow and &'.

The renal sympathetic neres seem to be most important in reducing &'The renal sympathetic neres seem to be most important in reducing &'during seere, acute disturbances, lasting for a few minutes to a few hours,during seere, acute disturbances, lasting for a few minutes to a few hours,such as those elicited by the defense reaction, brain ischemia, or seeresuch as those elicited by the defense reaction, brain ischemia, or seerehemorrhage. +n the healthy resting person, there appears to be littlehemorrhage. +n the healthy resting person, there appears to be littlesympathetic tone to the kidneys.sympathetic tone to the kidneys.


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&ngiotensin II #onstricts %fferent&ngiotensin II #onstricts %fferent

&rterioles&rterioles powerful renal asoconstrictor, angiotensin ++, can be powerful renal asoconstrictor, angiotensin ++, can be

considered as a circulating hormone as well as a locallyconsidered as a circulating hormone as well as a locallyproduced autacoid because it is formed in the kidneys as wellproduced autacoid because it is formed in the kidneys as wellas in the systemic circulation. !ecause angiotensin ++as in the systemic circulation. !ecause angiotensin ++preferentially constricts efferent arterioles, increasedpreferentially constricts efferent arterioles, increasedangiotensin ++ leels raise glomerular hydrostatic pressureangiotensin ++ leels raise glomerular hydrostatic pressurewhile reducing renal blood flow.while reducing renal blood flow.

+t should be kept in mind that increased angiotensin +++t should be kept in mind that increased angiotensin ++formation usually occurs in circumstances associated withformation usually occurs in circumstances associated withdecreased arterial pressure or olume depletion, which tend todecreased arterial pressure or olume depletion, which tend to

decrease &'decrease &' +ncreased angiotensin ++ leels that occur with a low3sodium+ncreased angiotensin ++ leels that occur with a low3sodium

diet or olume depletion help to presere &' and to maintaindiet or olume depletion help to presere &' and to maintaina normal e"cretion of metabolic waste products, such as ureaa normal e"cretion of metabolic waste products, such as ureaand creatinine, that depend on glomerular filtration for theirand creatinine, that depend on glomerular filtration for their

e"cretion.e"cretion.


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%ndothelial+'eri*ed Nitric ,ide 'ecreases Renal%ndothelial+'eri*ed Nitric ,ide 'ecreases Renal

-ascular Resistance and Increases "FR-ascular Resistance and Increases "FR

basal leel of nitric o"ide production appears to be basal leel of nitric o"ide production appears to beimportant for preenting e"cessie asoconstrictionimportant for preenting e"cessie asoconstrictionof the kidneys and allowing them to e"crete normalof the kidneys and allowing them to e"crete normalamounts of sodium and water.amounts of sodium and water.

dministration of drugs that inhibit the formation ofdministration of drugs that inhibit the formation ofnitric o"ide increases renal ascular resistance andnitric o"ide increases renal ascular resistance anddecreases &' and urinary sodium e"cretion,decreases &' and urinary sodium e"cretion,eentually causing high blood pressure.eentually causing high blood pressure.

+n some hypertensie patients, impaired nitric o"ide+n some hypertensie patients, impaired nitric o"ideproduction may contribute to renal asoconstrictionproduction may contribute to renal asoconstrictionand increased blood pressure.and increased blood pressure.


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Prostaglandins and Bradykinin TendProstaglandins and Bradykinin Tend

to Increase "FRto Increase "FR /ormones and autacoids that cause asodilation and increased/ormones and autacoids that cause asodilation and increased

renal blood flow and &' include the prostaglandins (&E 2renal blood flow and &' include the prostaglandins (&E 2and &12) and bradykinin.and &12) and bradykinin.

!y opposing asoconstriction of afferent arterioles, the!y opposing asoconstriction of afferent arterioles, the

prostaglandins may help to preent e"cessie reductions inprostaglandins may help to preent e"cessie reductions in&' and renal blood flow.&' and renal blood flow.

4nder stressful conditions, such as olume depletion or after4nder stressful conditions, such as olume depletion or aftersurgery, the administration of nonsteroidal anti3inflammatorysurgery, the administration of nonsteroidal anti3inflammatoryagents, such as aspirin, that inhibit prostaglandin synthesisagents, such as aspirin, that inhibit prostaglandin synthesismay cause significant reductions in &'.may cause significant reductions in &'.


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Function of nephroneFunction of nephrone -ideo-ideo
http://217.196.164.19/data/teacher/video/fiz_pat/Video1/F204353_nephron.mpghttp://217.196.164.19/data/teacher/video/fiz_pat/Video1/F204353_nephron.mpghttp://217.196.164.19/data/teacher/video/fiz_pat/Video1/F204353_nephron.mpg


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&UTR%"U!&TIN F "FR &N' R%N&!&UTR%"U!&TIN F "FR &N' R%N&!

B!' F!(B!' F!(

'eedback mechanisms intrinsic to the kidneys normally keep the renal'eedback mechanisms intrinsic to the kidneys normally keep the renalblood flow and &' relatiely constant, despite marked changes in arterialblood flow and &' relatiely constant, despite marked changes in arterialblood pressure. These mechanisms still function in blood3perfused kidneysblood pressure. These mechanisms still function in blood3perfused kidneysthal hae been remoed from the body, independent of systemic influences.thal hae been remoed from the body, independent of systemic influences.This relatie constancy of &' and renal blood flow is referred to asThis relatie constancy of &' and renal blood flow is referred to asautoregulation.autoregulation.

The primary function of blood flow autoregulation in most other tissuesThe primary function of blood flow autoregulation in most other tissues

besides the kidneys is to maintain deliery of o"ygen and nutrients to thebesides the kidneys is to maintain deliery of o"ygen and nutrients to thetissues at a normal leel and to remoe the waste products of metabolism,tissues at a normal leel and to remoe the waste products of metabolism,despite changes in the arterial pressure. +n the kidneys, the normal blooddespite changes in the arterial pressure. +n the kidneys, the normal bloodflow is much higher than re5uired for these functions. The major functionflow is much higher than re5uired for these functions. The major functionof autoregulation in the kidneys is to maintain a relatiely constant &'of autoregulation in the kidneys is to maintain a relatiely constant &'and to allow precise control of renal e"cretion of water and solutes. Theand to allow precise control of renal e"cretion of water and solutes. The

&' normally remains autoregulated (that is, remains relatiely constant),&' normally remains autoregulated (that is, remains relatiely constant),despite considerable arterial pressure fluctuations that occur during adespite considerable arterial pressure fluctuations that occur during aperson6s usual actiities. +n general, renal blood flow is autoregulated inperson6s usual actiities. +n general, renal blood flow is autoregulated inparallel with &', but &' is more efficiently autoregulated under certainparallel with &', but &' is more efficiently autoregulated under certainconditions.conditions.


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$yogenic &utoregulation of Renal$yogenic &utoregulation of Renal

Blood Flo. and "FRBlood Flo. and "FR second mechanism that contributes to the maintenance of a second mechanism that contributes to the maintenance of a

relatiely constant renal blood flow and &' is the ability ofrelatiely constant renal blood flow and &' is the ability ofindiidual blood essels to resist stretching during increasedindiidual blood essels to resist stretching during increasedarterial pressure, a phenomenon referred to as the myogenicarterial pressure, a phenomenon referred to as the myogenic

mechanism.mechanism. tretch of the ascular wall allows increased moement oftretch of the ascular wall allows increased moement of

calcium ions from the e"tracellular fluid into the cells, causingcalcium ions from the e"tracellular fluid into the cells, causingthem to contract through the mechanisms. This contractionthem to contract through the mechanisms. This contraction

preents oerdistention of the essel and at the same time, bypreents oerdistention of the essel and at the same time, by

raising ascular resistance, helps to preent e"cessieraising ascular resistance, helps to preent e"cessieincreases in renal blood flow and &' when arterial pressureincreases in renal blood flow and &' when arterial pressureincreases.increases.


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URIN% FR$&TINURIN% FR$&TIN The rates at which different substances are e"creted in theThe rates at which different substances are e"creted in the

urine represent the sum of three renal processes, (1)urine represent the sum of three renal processes, (1)glomerular filtration, (2) reabsorption of substances from theglomerular filtration, (2) reabsorption of substances from therenal tubules into the blood, and (7) secretion of substancesrenal tubules into the blood, and (7) secretion of substancesfrom the blood into the renal tubules.from the blood into the renal tubules.

E"pressed mathematically,E"pressed mathematically, 4rinary e"cretion rate 8 'iltration rate4rinary e"cretion rate 8 'iltration rate 3 eabsorption rate 9 ecretion rate3 eabsorption rate 9 ecretion rate


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4rine formation4rine formationbegins with filtrationbegins with filtrationfrom the glomerularfrom the glomerular

capillaries intocapillaries into!owman6s capsule of!owman6s capsule ofa large amount of fluida large amount of fluidthat is irtually free ofthat is irtually free of

protein.protein.

*ost substances in the*ost substances in theplasma, e"cept forplasma, e"cept forproteins, are freelyproteins, are freelyfiltered so that theirfiltered so that theirconcentrations in theconcentrations in theglomerular filtrate inglomerular filtrate in!owman6s capsule are!owman6s capsule arealmost the same as inalmost the same as inthe plasma.the plasma.


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(hy &re !arge &)ounts of Solutes Filtered(hy &re !arge &)ounts of Solutes Filtered

and Then Rea/sor/ed /y the Kidneys0and Then Rea/sor/ed /y the Kidneys0

:ne adantage of a high &' is that it allows the kidneys to:ne adantage of a high &' is that it allows the kidneys torapidly remoe waste products from the body that dependrapidly remoe waste products from the body that depend

primarily on glomerular filtration for their e"cretion. *ostprimarily on glomerular filtration for their e"cretion. *ostwaste products are poorly reabsorbed by the tubules and,waste products are poorly reabsorbed by the tubules and,therefore, depend on a high &' for effectie remoal fromtherefore, depend on a high &' for effectie remoal fromthe body.the body.

second adantage of a high &' is that it allows all the second adantage of a high &' is that it allows all thebody fluids to be filtered and processed by the kidney manybody fluids to be filtered and processed by the kidney manytimes each day. !ecause the entire plasma olume is onlytimes each day. !ecause the entire plasma olume is onlyabout 7 liters, whereas the &' is about 1;#


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"lo)erular #apillary $e)/rane"lo)erular #apillary $e)/rane

The glomerular capillary membrane is similar to thatThe glomerular capillary membrane is similar to thatof other capillaries, e"cept that it has three (instead ofof other capillaries, e"cept that it has three (instead ofthe usual two) major layers>the usual two) major layers>

(1) the endothelium of the capillary,(1) the endothelium of the capillary, (2) a basement membrane, and(2) a basement membrane, and (7) a layer of epithelial cells (podocytes) surrounding(7) a layer of epithelial cells (podocytes) surrounding

the outer surface of the capillary basement membrane.the outer surface of the capillary basement membrane. Together, these layers make up the filtration barrierTogether, these layers make up the filtration barrier

that, despite the three layers, filters seeral hundredthat, despite the three layers, filters seeral hundredtimes as much water and solutes as the usual capillarytimes as much water and solutes as the usual capillarymembrane.membrane.


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"lo)erular #apillary $e)/rane"lo)erular #apillary $e)/rane

lthough the fenestrations are relatiely large,lthough the fenestrations are relatiely large,

endothelial cells are richly endowed with fi"edendothelial cells are richly endowed with fi"ed

negatie charges that hinder the passage ofnegatie charges that hinder the passage of

plasma proteins.plasma proteins.

The basement membrane effectiely preentsThe basement membrane effectiely preents

filtration of plasma proteins.filtration of plasma proteins.


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PodocytesPodocytes The final part of theThe final part of the

glomerularglomerularmembrane is a layermembrane is a layerof epithelial cellsof epithelial cells

(podocytes) that(podocytes) thatencircle the outerencircle the outersurface of thesurface of thecapillaries.capillaries.

The foot processesThe foot processesare separated byare separated by

gaps called slitgaps called slitpores throughpores throughwhich thewhich theglomemlar filtrateglomemlar filtratemoes. Themoes. Theepithelial cells,epithelial cells,which also haewhich also haenegatie charges,negatie charges,

proide additionalproide additionalrestriction torestriction tofiltration of plasmafiltration of plasma

proteins.proteins.


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Three /asic renal processesThree /asic renal processes

The substance is freely filtered but is alsoThe substance is freely filtered but is alsopartly reabsorbed from the tubules back intopartly reabsorbed from the tubules back intothe blood.the blood.

'or each substance in the plasma, a particular'or each substance in the plasma, a particularcombination of filtration, reabsorption, andcombination of filtration, reabsorption, andsecretion occurs. The rate at which thesecretion occurs. The rate at which the

substance is e"creted in the urine depends onsubstance is e"creted in the urine depends onthe relatie rates of these three basic renalthe relatie rates of these three basic renalprocesses.processes.


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Filtration1 Rea/sorption1 andFiltration1 Rea/sorption1 and

Secretion of 'ifferent Su/stancesSecretion of 'ifferent Su/stances

+n general, tubular, reabsorption is 5uantitatiely more+n general, tubular, reabsorption is 5uantitatiely moreimportant than tubular secretion in the formation of urine, butimportant than tubular secretion in the formation of urine, butsecretion plays an important role in determining the amountssecretion plays an important role in determining the amounts

of potassium and hydrogen ions and a few other substancesof potassium and hydrogen ions and a few other substancesthat are e"creted in the urine.that are e"creted in the urine. *ost substances that must be cleared from the blood,*ost substances that must be cleared from the blood,

especially the end products of metabolism such as urea,especially the end products of metabolism such as urea,creatinine, uric acid, and urates, are poorly reabsorbed and are,creatinine, uric acid, and urates, are poorly reabsorbed and are,therefore, e"creted in large amounts in the urine.therefore, e"creted in large amounts in the urine.

-ertain foreign substances and drugs are also poorly-ertain foreign substances and drugs are also poorlyreabsorbed but, in addition, are secreted from the blood intoreabsorbed but, in addition, are secreted from the blood intothe tubules, so that their e"cretion rates are high.the tubules, so that their e"cretion rates are high.


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Filtration1 Rea/sorption1 andFiltration1 Rea/sorption1 and

Secretion of 'ifferent Su/stancesSecretion of 'ifferent Su/stances

utritional substances, such as amino acidsutritional substances, such as amino acids

and glucose, are completely reabsorbed fromand glucose, are completely reabsorbed from

the tubules and do not appear in the urine eenthe tubules and do not appear in the urine een

though large amounts are filtered by thethough large amounts are filtered by the

glomerular capillaries. Each of the processes 3glomerular capillaries. Each of the processes 3

glomerular filtration, tubular reabsorption, andglomerular filtration, tubular reabsorption, and

tubular secretion 3 is regulated according to thetubular secretion 3 is regulated according to theneeds of the body.needs of the body.


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Tu/ular rea/sorptionTu/ular rea/sorption


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Tu/ular secretionTu/ular secretion


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#ountercurrent )ecanis) and#ountercurrent )ecanis) and

concentration of urineconcentration of urine


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$U!TIP!% FUN#TINS F TH% KI'N%YS IN$U!TIP!% FUN#TINS F TH% KI'N%YS IN

H$%ST&SISH$%ST&SIS E"cretion of metabolicE"cretion of metabolic

waste products and foreignwaste products and foreignchemicalschemicals

egulation of water andegulation of water andelectrolyte balanceselectrolyte balances

egulation of body fluidegulation of body fluid

osmolality and electrolyteosmolality and electrolyteconcentrationsconcentrations

egulation of acid3baseegulation of acid3basebalancebalance

egulation of arterialegulation of arterial

pressurepressure ecretion, metabolism, andecretion, metabolism, and

e"cretion of hormonese"cretion of hormones &luconeogenesis&luconeogenesis


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Regulation of (ater and %lectrolyteRegulation of (ater and %lectrolyte

BalancesBalances 'or maintenance of homeostasis, e"cretion of water and electrolytes'or maintenance of homeostasis, e"cretion of water and electrolytes

must precisely match intake. +f intake e"ceeds e"cretion, the amountmust precisely match intake. +f intake e"ceeds e"cretion, the amountof that substance in the body will increase. +f intake is less thanof that substance in the body will increase. +f intake is less thane"cretion, the amount of that substance in the body will decrease.e"cretion, the amount of that substance in the body will decrease.+ntakes of water and many electrolytes usually are goerned mainly+ntakes of water and many electrolytes usually are goerned mainly

by a person6s eating and drinking habits, necessitating that theby a person6s eating and drinking habits, necessitating that thekidneys adjust their e"cretion rates to match intakes of the ariouskidneys adjust their e"cretion rates to match intakes of the arioussubstances.substances.

?ithin 2 to 7 days after raising sodium intake, renal e"cretion also?ithin 2 to 7 days after raising sodium intake, renal e"cretion alsoincreases to about 7## mE5$day, so that a balance between intakeincreases to about 7## mE5$day, so that a balance between intakeand output is re3established. /oweer, during the 2 to 7 days ofand output is re3established. /oweer, during the 2 to 7 days of

renal adaptation to the high sodium intake, there is a modestrenal adaptation to the high sodium intake, there is a modestaccumulation of sodium that raises e"tracellular fluid olumeaccumulation of sodium that raises e"tracellular fluid olumeslightly and triggers hormonal changes and other compensatoryslightly and triggers hormonal changes and other compensatoryresponses that signal the kidneys to increase their sodium e"cretion.responses that signal the kidneys to increase their sodium e"cretion.


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Regulation of &rterial PressureRegulation of &rterial Pressure

+n addition, the+n addition, thekidneys contributekidneys contributeto short3termto short3termarterial pressurearterial pressureregulation byregulation by

secretingsecretingasoactie factorsasoactie factorsor substances, suchor substances, suchas renin, that leadas renin, that leadto formation ofto formation ofasoactieasoactie

products (forproducts (fore"ample,e"ample,angiotensin ++).angiotensin ++).

The kidneys play a dominant role inThe kidneys play a dominant role inlongterm regulation of arteriallongterm regulation of arterial

pressure by e"creting ariablepressure by e"creting ariableamounts of sodium and water.amounts of sodium and water.


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Regulation of &cid+Base BalanceRegulation of &cid+Base Balance

The kidneys contribute to acid3base regulation, along with theThe kidneys contribute to acid3base regulation, along with thelungs and body fluid buffers, by e"creting acids and bylungs and body fluid buffers, by e"creting acids and byregulating the body fluid buffer stores. The kidneys are theregulating the body fluid buffer stores. The kidneys are theonly means for eliminating from the body certain types ofonly means for eliminating from the body certain types of

acids generated by metabolism of proteins, such as sup furicacids generated by metabolism of proteins, such as sup furicacid and phosphoric acid. kidneys is hypo"ia. +n the normalacid and phosphoric acid. kidneys is hypo"ia. +n the normalperson, the kidneys account for almost all the erythropoietinperson, the kidneys account for almost all the erythropoietinsecreted into the circulation.secreted into the circulation.

+n people with seere kidney disease or who hae had their+n people with seere kidney disease or who hae had their

kidneys remoed and hae been placed on hemodialysis,kidneys remoed and hae been placed on hemodialysis,seere anemia deelops as a result of decreased erythropoietinseere anemia deelops as a result of decreased erythropoietin

production.production.


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Regulation of 2134+'ihydro,yRegulation of 2134+'ihydro,y

-ita)in ' 5 Production-ita)in ' 5 Production

The kidneys produce the actie form ofThe kidneys produce the actie form ofitamin , 1,2@3dihydro"y itamin 7itamin , 1,2@3dihydro"y itamin 7(calcitriol) by hydro"ylating this itamin at the(calcitriol) by hydro"ylating this itamin at the

number A1A position.number A1A position. -alcitriol is essential for normal calcium-alcitriol is essential for normal calcium

deposition in bone and calcium reabsorptiondeposition in bone and calcium reabsorption

by the gastrointestinal tract. -alcitriol plays anby the gastrointestinal tract. -alcitriol plays animportant role in calcium and phosphateimportant role in calcium and phosphateregulation.regulation.


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"lucose Synthesis"lucose Synthesis

The kidneys synthesi0e glucose from amino acids and otherThe kidneys synthesi0e glucose from amino acids and otherprecursors during prolonged fasting, a process referred to asprecursors during prolonged fasting, a process referred to asgluconeogenesis. The kidneys6 capacity to add glucose to thegluconeogenesis. The kidneys6 capacity to add glucose to the

blood during prolonged periods of fasting rials that of theblood during prolonged periods of fasting rials that of thelier.lier.

?ith chronic kidney disease or acute failure of the kidneys,?ith chronic kidney disease or acute failure of the kidneys,these homeostatic functions are disrupted, and seerethese homeostatic functions are disrupted, and seereabnormalities of body fluid olumes and composition rapidlyabnormalities of body fluid olumes and composition rapidlyoccur. ?ith complete renal failure, enough accumulation in theoccur. ?ith complete renal failure, enough accumulation in the

body of potassium, acids, fluid, and other substances occursbody of potassium, acids, fluid, and other substances occurs

within a few days to cause death, unless clinical interentionswithin a few days to cause death, unless clinical interentionssuch as hemodialysis are initiated to restore, at least partially,such as hemodialysis are initiated to restore, at least partially,the body fluid and electrolyte balances.the body fluid and electrolyte balances.


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B&SI# PRIN#IP!%S F S$SISB&SI# PRIN#IP!%S F S$SIS

&N' S$TI# PR%SSUR%&N' S$TI# PR%SSUR% :smosis is6 the net diffusion of water across a selectiely:smosis is6 the net diffusion of water across a selectiely

permeable membrane from a region of high waterpermeable membrane from a region of high waterconcentration to one thai has a lower water concentration.concentration to one thai has a lower water concentration.?hen a solute is added to pure water, this reduces the?hen a solute is added to pure water, this reduces theconcentration of water in the mi"ture.concentration of water in the mi"ture.

+f a solute such as sodium chloride is added to the e"tracellular+f a solute such as sodium chloride is added to the e"tracellularfluid, water rapidly diffuses from the cells through the cellfluid, water rapidly diffuses from the cells through the cellmembranes into the e"tracellular fluid until the watermembranes into the e"tracellular fluid until the waterconcentration on both sides of the membrane becomes e5ual.concentration on both sides of the membrane becomes e5ual.-onersely, if a solute such as sodium chloride is remoed-onersely, if a solute such as sodium chloride is remoed

from the e"tracellular fluid, thereby raising the waterfrom the e"tracellular fluid, thereby raising the waterconcentration, water diffuses from the e"tracellular fluidconcentration, water diffuses from the e"tracellular fluidthrough the cell membranes and into the cells. The rate ofthrough the cell membranes and into the cells. The rate ofdiffusion of water is called the rate of osmosis.diffusion of water is called the rate of osmosis.


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Isos)otic1 Hyperos)otic1 and Hypo+Isos)otic1 Hyperos)otic1 and Hypo+

os)otic Fluidsos)otic Fluids olutions with an osmolarity the same as the cell are called isosmotic,olutions with an osmolarity the same as the cell are called isosmotic,

regardless of whether the solute can penetrate the cell membrane.regardless of whether the solute can penetrate the cell membrane. The terms hyperosmotic and hypo3osmotic refer to solutions that hae aThe terms hyperosmotic and hypo3osmotic refer to solutions that hae a

higher osmolarity or lower osmolarity, respectiely, compared with thehigher osmolarity or lower osmolarity, respectiely, compared with thenormal e"tracellular fluid, without regard for whether the solute permeatesnormal e"tracellular fluid, without regard for whether the solute permeatesthe cell membrane.the cell membrane.

/ighly permeating substances, such as urea, can cause transient shifts in/ighly permeating substances, such as urea, can cause transient shifts influid olumes between the intracellular and e"tracellular fluids, but gienfluid olumes between the intracellular and e"tracellular fluids, but gienenough time, the concentrations of these substances eentually becomeenough time, the concentrations of these substances eentually becomee5ual in the two compartments and hae little effect on intracellulare5ual in the two compartments and hae little effect on intracellularolume under steady3state conditions.olume under steady3state conditions.

'luid usually enters the body through the gut and must be transported by'luid usually enters the body through the gut and must be transported bythe blood to all tissues before complete osmotic e5uilibrium can occur. +tthe blood to all tissues before complete osmotic e5uilibrium can occur. +tusually takes about 7# minutes to achiee osmotic e5uilibrium eerywhereusually takes about 7# minutes to achiee osmotic e5uilibrium eerywherein the body after drinking water.in the body after drinking water.


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S$R%#%PTR+&'H F%%'BK SYST%$S$R%#%PTR+&'H F%%'BK SYST%$

1. n increase in e"tracellular fluid osmolarity causes the1. n increase in e"tracellular fluid osmolarity causes thespecial nere cells called osmoreceptor cells, located in thespecial nere cells called osmoreceptor cells, located in theanterior hypothalamus near the supraoptic nuclei, to shrink.anterior hypothalamus near the supraoptic nuclei, to shrink.

2. hrinkage of the osmoreceptor cells causes them to fire,2. hrinkage of the osmoreceptor cells causes them to fire,sending nere signals to additional nere cells in thesending nere signals to additional nere cells in thesupraoptic nuclei, which then relay these signals down thesupraoptic nuclei, which then relay these signals down thestalk of the pituitary gland to the posterior pituitary.stalk of the pituitary gland to the posterior pituitary.

7. These action potentials conducted to the posterior pituitary7. These action potentials conducted to the posterior pituitarystimulate the release of /, which is stored in secretorystimulate the release of /, which is stored in secretorygranules (or esicles) in the nere endings.granules (or esicles) in the nere endings.

B. / enters the blood stream and is transported to theB. / enters the blood stream and is transported to thekidneys, where it increases the water permeability of the latekidneys, where it increases the water permeability of the late

distal tubules, cortical collecting tubules, and inner medullarydistal tubules, cortical collecting tubules, and inner medullarycollecting ducts.collecting ducts.

@. The increased water permeability in the distal nephron@. The increased water permeability in the distal nephronsegments causes increased water reabsorption and e"cretion ofsegments causes increased water reabsorption and e"cretion ofa small olume of concentrated urine.a small olume of concentrated urine.


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& second neuronal& second neuronal

areaarea

second neuronal area second neuronal areaimportant in controllingimportant in controllingosmolarity and /osmolarity and /secretion is locatedsecretion is located

along the anteroentralalong the anteroentralregion of the thirdregion of the thirdentricle, called theentricle, called the+$7% region.+$7% region.


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R!% F THIRST IN #NTR!!IN"R!% F THIRST IN #NTR!!IN"

%6TR%!!U!&R F!UI' S$!&RITY &N'%6TR%!!U!&R F!UI' S$!&RITY &N'

S'IU$ #N#%NTR&TINS'IU$ #N#%NTR&TIN

The kidneys minimi0e fluid loss during water deficits throughThe kidneys minimi0e fluid loss during water deficits throughthe osmoreceptor3/ feedback system. de5uate fluidthe osmoreceptor3/ feedback system. de5uate fluidintake, howeer, is necessary to counterbalance whateer fluidintake, howeer, is necessary to counterbalance whateer fluidloss does occur through sweating and breathing and throughloss does occur through sweating and breathing and through

the gastrointestinal tract.the gastrointestinal tract. 'luid intake is regulated by the thirst mechanism, which,'luid intake is regulated by the thirst mechanism, which,

together with the osmoreceptor3/ mechanism, maintainstogether with the osmoreceptor3/ mechanism, maintainsprecise control of e"tracellular fluid osmolarity and sodiumprecise control of e"tracellular fluid osmolarity and sodiumconcentration. *any of the same factors that stimulate /concentration. *any of the same factors that stimulate /

secretion also increase thirst, which is defined as the conscioussecretion also increase thirst, which is defined as the consciousdesire for water.desire for water.


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#entral Ner*ous Syste) #enters for Thirst#entral Ner*ous Syste) #enters for Thirst


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Sti)uli for ThirstSti)uli for Thirst :ne of the most important is increased e"tracellular fluid:ne of the most important is increased e"tracellular fluid

osmolarity, which causes intracellular dehydration in the thirstosmolarity, which causes intracellular dehydration in the thirstcenters, thereby stimulating the sensation of thirst. The aluecenters, thereby stimulating the sensation of thirst. The alueof this response is obious> it helps to dilute e"tracellularof this response is obious> it helps to dilute e"tracellularfluids and returns osmolarity toward normal.fluids and returns osmolarity toward normal.

ecreases in e"tracellular fluid olume and arterial pressureecreases in e"tracellular fluid olume and arterial pressure

also stimulate thirst by a pathway that is independent of thealso stimulate thirst by a pathway that is independent of theone stimulated by increased plasma osmolarity. Thus, bloodone stimulated by increased plasma osmolarity. Thus, bloodolume loss by hemorrhage stimulates thirst een though thereolume loss by hemorrhage stimulates thirst een though theremight be no change in plasma osmolarity.might be no change in plasma osmolarity.

This probably occurs because of neutral input fromThis probably occurs because of neutral input fromcardiopulmonary and systemic arterial baroreceptors in thecardiopulmonary and systemic arterial baroreceptors in thecirculation. third important stimulus for thirst is angiotensincirculation. third important stimulus for thirst is angiotensin++. tudies in animals hae shown that angiotensin ++ acts on++. tudies in animals hae shown that angiotensin ++ acts onthe subfornical organ and on the organum asculosum of thethe subfornical organ and on the organum asculosum of thelamina terminalis.lamina terminalis.


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Sti)uli for ThirstSti)uli for Thirst These regions are outside the blood3brain barrier, and peptidesThese regions are outside the blood3brain barrier, and peptides

such as angiotensin ++ diffuse into the tissues. !ecausesuch as angiotensin ++ diffuse into the tissues. !ecauseangiotensin ++ is also stimulated by factors associated withangiotensin ++ is also stimulated by factors associated withhypoolemia and low blood pressure, its effect on thirst helpshypoolemia and low blood pressure, its effect on thirst helpsto restore blood olume and blood pressure toward normal,to restore blood olume and blood pressure toward normal,along with the other actions of angiotensin ++ on the kidneys toalong with the other actions of angiotensin ++ on the kidneys to

decrease fluid e"cretion.decrease fluid e"cretion. ryness of the mouth and mucous membranes of theryness of the mouth and mucous membranes of the

esophagus can elicit the sensation of thirst. s a result, a thirstyesophagus can elicit the sensation of thirst. s a result, a thirstyperson may receie relief from thirst almost immediately afterperson may receie relief from thirst almost immediately afterdrinking water, een though the water has not been absorbeddrinking water, een though the water has not been absorbed

from the gastrointestinal tract and has not yet had an effect onfrom the gastrointestinal tract and has not yet had an effect one"tracellular fluid osmolarity. &astrointestinal and pharyngeale"tracellular fluid osmolarity. &astrointestinal and pharyngealstimuli influence thirst. 'or e"ample, in animals that hae anstimuli influence thirst. 'or e"ample, in animals that hae anesophageal opening to the e"terior so that water is neeresophageal opening to the e"terior so that water is neerabsorbed into the blood, partial relief of thirst occurs afterabsorbed into the blood, partial relief of thirst occurs afterdrinking, although the relief is only temporary.drinking, although the relief is only temporary.


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Threshold for s)olar Sti)ulus of 'rinkingThreshold for s)olar Sti)ulus of 'rinking

The kidneys must continually e"crete at least some fluid, eenThe kidneys must continually e"crete at least some fluid, een

in a dehydrated person, to rid the body of e"cess solutes thatin a dehydrated person, to rid the body of e"cess solutes thatare ingested or produced by metabolism. ?ater is also lost byare ingested or produced by metabolism. ?ater is also lost byeaporation from the lungs and the gastrointestinal tract andeaporation from the lungs and the gastrointestinal tract and

by eaporation and sweating from the skin. Therefore, there isby eaporation and sweating from the skin. Therefore, there isalways a tendency for dehydration, with resultant increasedalways a tendency for dehydration, with resultant increased

e"tracellular fluid sodium concentration and osmolarity.e"tracellular fluid sodium concentration and osmolarity.

?hen the sodium concentration increases only about 2 mE5$


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#ardio*ascular Refle, Sti)ulation of &'H Release#ardio*ascular Refle, Sti)ulation of &'H Release

/y 'ecreased &rterial Pressure and7or/y 'ecreased &rterial Pressure and7or

'ecreased Blood -olu)e'ecreased Blood -olu)e

/ release is also controlled by cardioascular refle"es in response to/ release is also controlled by cardioascular refle"es in response todecreases in blood pressure and$or blood olume, including (1) the arterialdecreases in blood pressure and$or blood olume, including (1) the arterial

baroreceptor refle"es and (2) the cardiopulmonary refle"es. These refle"baroreceptor refle"es and (2) the cardiopulmonary refle"es. These refle"pathways originate in high3pressure regions of the circulation, such as thepathways originate in high3pressure regions of the circulation, such as theaortic arch and carotid sinus, and in the low3pressure regions, especially inaortic arch and carotid sinus, and in the low3pressure regions, especially inthe cardiac atria. fferent stimuli are carried by the agus andthe cardiac atria. fferent stimuli are carried by the agus and

glossopharyngeal neres with synapses in the nuclei of the tractusglossopharyngeal neres with synapses in the nuclei of the tractussolitarius. rojections from these nuclei relay signals to the hypothalamicsolitarius. rojections from these nuclei relay signals to the hypothalamicnuclei that control / synthesis and secretion.nuclei that control / synthesis and secretion.

Thus, in addition to increased osmolarity, two other stimuli increase /Thus, in addition to increased osmolarity, two other stimuli increase /secretion> (1) decreased arterial pressure and (2) decreased blood olume.secretion> (1) decreased arterial pressure and (2) decreased blood olume.?heneer blood pressure and blood olume are reduced, such as occurs?heneer blood pressure and blood olume are reduced, such as occurs

during hemorrhage, increased / secretion causes increased fluidduring hemorrhage, increased / secretion causes increased fluidreabsorption by the kidneys, helping to restore blood pressure and bloodreabsorption by the kidneys, helping to restore blood pressure and bloodolume toward normal.olume toward normal.


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Role of &ngiotensin II and &ldosterone inRole of &ngiotensin II and &ldosterone in


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Role of &ngiotensin II and &ldosterone inRole of &ngiotensin II and &ldosterone in

#ontrolling %,tracellular Fluid s)olarity and#ontrolling %,tracellular Fluid s)olarity and

Sodiu) #oncentrationSodiu) #oncentration

!oth angiotensin ++ and aldosterone play an important role in regulating!oth angiotensin ++ and aldosterone play an important role in regulatingsodium reabsorption by the renal tubules. ?hen sodium intake is low,sodium reabsorption by the renal tubules. ?hen sodium intake is low,increased leels of these hormones stimulate sodium reabsorption by theincreased leels of these hormones stimulate sodium reabsorption by thekidneys and, therefore, preent large sodium losses, een though sodiumkidneys and, therefore, preent large sodium losses, een though sodiumintake may be reduced to as low as 1# per cent of normal. -onersely, withintake may be reduced to as low as 1# per cent of normal. -onersely, withhigh sodium intake, decreased formation of these hormones permits thehigh sodium intake, decreased formation of these hormones permits the

kidneys to e"crete large amounts of sodium. !ecause of the importance ofkidneys to e"crete large amounts of sodium. !ecause of the importance ofangiotensin ++ and aldosterone in regulating sodium e"cretion by theangiotensin ++ and aldosterone in regulating sodium e"cretion by thekidneys, one might mistakenly infer that they also play an important role inkidneys, one might mistakenly infer that they also play an important role inregulating e"tracellular fluid sodium concentration. lthough theseregulating e"tracellular fluid sodium concentration. lthough thesehormones increase the amount of sodium in the e"tracellular fluid, theyhormones increase the amount of sodium in the e"tracellular fluid, theyalso increase the e"tracellular fluid olume by increasing reabsorption ofalso increase the e"tracellular fluid olume by increasing reabsorption ofwater along with the sodium. Therefore. angiotensin / and aldosteronewater along with the sodium. Therefore. angiotensin / and aldosteronehae little effect on sodium concentration, e"cept under e"tremehae little effect on sodium concentration, e"cept under e"tremeconditions.conditions.


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S&!T &PP%TIT% $%#H&NIS$ FR #NTR!!IN"S&!T &PP%TIT% $%#H&NIS$ FR #NTR!!IN"


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S&!T+&PP%TIT% $%#H&NIS$ FR #NTR!!IN"S&!T+&PP%TIT% $%#H&NIS$ FR #NTR!!IN"

%6TR%!!U!&R F!UI' S'IU$ #N#%NTR&TIN%6TR%!!U!&R F!UI' S'IU$ #N#%NTR&TIN

&N' -!U$%&N' -!U$%

*aintenance of normal e"tracellular fluid olume and sodium*aintenance of normal e"tracellular fluid olume and sodiumconcentration re5uires a balance between sodium e"cretion andconcentration re5uires a balance between sodium e"cretion andsodium intake. +n modern ciili0ations, sodium intake is almostsodium intake. +n modern ciili0ations, sodium intake is almostalways greater than necessary for homeostasis. 4sual highalways greater than necessary for homeostasis. 4sual highsodium intake may contribute to cardioascular disorders such assodium intake may contribute to cardioascular disorders such as

hypertension.hypertension. alt appetite is due in part to the fact that animals and humansalt appetite is due in part to the fact that animals and humans

like salt and eat it regardless of whether they are saltdeficient.like salt and eat it regardless of whether they are saltdeficient.There is also a regulatory component to salt appetite in whichThere is also a regulatory component to salt appetite in whichthere is a behaioral drie to obtain salt when there is sodiumthere is a behaioral drie to obtain salt when there is sodium

deficiency in the body.deficiency in the body. +n general, the two primary stimuli that are belieed to e"cite+n general, the two primary stimuli that are belieed to e"cite

salt appetite are (1) decreased e"tracellular fluid sodiumsalt appetite are (1) decreased e"tracellular fluid sodiumconcentration and (2) decreased blood olume or blood pressure,concentration and (2) decreased blood olume or blood pressure,associated with circulatory insufficiency.associated with circulatory insufficiency.


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physiology of the renal system

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