PHYSIO Notes - Renal

7/31/2019 PHYSIO Notes - Renal

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CHAPTER

EXCRETORY SYSTE

Excretory SystemKidney Blood VesselsKidney - StructureJuxtaglomerular ApparatusUrine FormationForces Involved in FiltrationWater Reabsorption - Pr oxi ma l TubuleWater Reabsorption - Distal and Collecting TubulesFunction of the Loop of HenleRole of Urea in the Counter-Current MechanismFunction of the Vasa RectaMaintenance of Acid-Base BalanceSodium ReabsorptionDefence of Body Fluid VolumeRenal Regulation of Potassium ExcretionDefence of Body Fluid TonacityPlasma ClearanceThe 'Clearance' of Inulin in the NephronUrea 'Clearance'PAH 'Clearance'Urinary Bladder and UretersStorage and Expulsion of UrineUrine

166167168169170171172173, 174175, 176177178179-181182183184185186187188189190191192


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EXCRETORY SYSTE M

EXCRETORY SYSTEM

The RENAL ARTERY divides into/ INTERLOBAR ARTERIES",'-' +_ I/. : divide into ' ARCUAT. .. : A % ' " .- . _ - c _______ ..... . '< , ... _. ; : : ;- ------- - . . ----: give rise to -z: ....y .. - - ... -/ :: . STRAIGHT . -.....-; :...:..... - '-:--'-=-==f .: . :-ARTERIES - . _" -:-..:. I : '":... - . - ......... --------- .. - . .... - from which arise - .. '-,:- - -' - AFFERENT - __-

'-.;: ....:..::-- . --..... - ---- ...... .... .. ------.-:

\ \

Each Afferent Arteriole . divides into a t uf t o f i Icapillaries which stay 1,close together t o f or m I

the GLOMERULUS(or glomerular capillaries).

Al l t he glomeruli lie within th e cortex of th e kidney. The capillariesof each glomerulus rejoin to form an efferent arteriole.

arteriesare also cal ledINTERLOBULAR

arteries

I

.. _ .:-- -,. .BLADDER - - - - - - - - - -

" , '"storage and ../ ....expulsion of ....URINE ",,,,,,,,,,,'"URETHRA

KIDNEYS - - - ...."formationof URINE ....' J1,...,...;'.

\,...../ --------.:':._-------URETERS

The respiratory system, the skin and the kidneys are the chief excretory organs of thebody .Function of the KidneysThe kidneys adjust loss of water and electrolytes from the body to keep body fluidsconstant in amount and composition. They excrete waste products of metabolism, foreignchemicals such as drugs and food additives, secrete the hormones renin and erythropoietinand they activate vitamin D.

They are involved in blood pressure regulation since, in controlling sodium balance, theyalso control total body water and extracellular volume . The renin-angiotensin systemis similarly involved. They produce such vasoactive substances as prostaglandins which can

be constrictor or dilator, and bradykininthe vasodilator peptide.

To understand the way inwhich the kidney carries ou tthese functions, it is essential tounderstand first the way inwhich it is supplied with blood.About 25% of the leftventricle's output of blood ineach cardiac cycle is distributedto the kidneys for filtration.

166


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EXCRETORY SYST

KIDNEY BLOOD VESSEL

The route taken by the blood after it passes through the efferent arterioles depends onwhether the efferent arter ioles are from a juxta-medullary (next to the medulla) glomerulusor an ou ter cortical glomerulus. - --

, ARCUATE, ARTERY- - -----------CORTICO -MEDULLARYJUNCTIONARCUATE VEIN

VASA RECTA-formed by efferent arteriole of juxta-medullary glomerulus branching to formcapillaries. These form long loops whichrun d ow n i nt o the medulla and surroundcollecting ducts, then run back up andjo in arcuate vein.

",,/OUTER CORTICAL GLOMERULAR;' CAPILLARIES

,; EFFERENT ARTERIOLE -;; gives rise to a second network ofcapillaries which are confined tothe cortex, hence surround proximaland distal convoluted tubules andcortical part of collecting tubu les,then join inter lobar vein which joinsthe arcuate vein.

AFFERENTARTERIOLES\\\\\,

\,,

STRAIGHT .........ARTERY

EFFERENT / "ARTERIOLE

JUXTA-MEDULLARYGLOMERULUS

-

CORTEX

-- - - - - - -

The efferent ar terioles are narrower than the afferen t which causes a h igher pressu re inthe glomerular capillaries than in capillaries in other parts of th e body.

Arcuate veins join to form interlobar veins which then join to form renal vein.


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EXCRETORY SYSTEM

KIDN EY -STRUCTURE

Each kidney contains approximately one million functional units - nepbrons - which formurine.

In the tubules

Ascending limbof loop of Henle-- - - - contactsafferent andefferent arteriolesand becomes thedistalconvolutedtubule.

urineformation iscompleted by

REABSORPTIONacross the tubulewalls into theblood stream

of somesubstancesand bySECRETION

from the bloodinto the tubule ofothers; andSYNTHESISin tubular cells of

other substances.F..--1-- - - COLLECTING

TUBULESempty formedurine into thepelvis of thekidney at the

tip of the pyramid(papilla).

\

II

DESCENDINGAND \ ASCENDlNG --LIMBS OFLOOPOFHENLE

PELVIS

..--ROXIMALCONVOLUTEDTUBULE

Each AFFERENT ARTERIOLE "',_leads to a tuft of GLOMERULAR ' ,capillaries. - __-urrounding this tuft is the closed end - BOWMAN'S CAPSULE - - - - - -- of a long tortuousRENAL TUBULE whichhas various parts -

In the renalcorpuscleurme

formationstarts withfiltrationof the blood

168


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EXC RETO RY SY

JUXTAGLOMERULAR APPARAT

As the ascending limb o f th e loop of Henle passes between th e afferent an d efferentarterioles to become th e distal convoluted tubule, th e cells in this part o f t he n e ph r on aredifferent an d form what is called th e m a c u la densa . These cells, nearest th e glomerulartuft, a re smalle r t han t he rest o f the convoluted tubule cells an d form on e part of th ejuxtaglomerular apparatus (JGA). T h e two other parts of th e JG A are th e granular orjuxtaglomerular cells and the la cis or e x t raglom e r u lar m esan gia l cells .

- BOWMAN's SPACE

_ .... EFFERENT-. - - ARTERIOLELACIS CELLS orextraglomerular

mesangial cellsUnknown function bu t

they contain ren in .

DISTAL CONVOLUTEDTUBULE

- - - PROXIMALCONVOLUTED TUBULE

- -li6t-- MESANGIAL CELLSFound between theglomerular capillaryloops. They are

" contractile and playa.\.. role in cont rolling filtration (not part of the JGA).

:"..

--LOMERULAR -CAPILLARIES

SYMPATHETICNERVES

MACULA DENSA" Cells detect fall in Na" and cr in I tubule and cause renin secretion.

GRANULAR orJUXTAGLOMERULAR CELLS "Epithe lioid cel ls withmembrane-bound granulesin wall of the afferentand efferent arterioleswh ich secrete renin .

Renin is secreted by th e juxtaglomerular cells in response to a decrease in extracellularfluid volume an d blood pressure or an increase in sympath etic nerve activity. In addition, afall in t ub ul ar N a '" an d cr is detec ted by th e macula densa an d causes an increased renin

secretion.


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EXCRETORY SYSTEM

URINE FORMATION

Urine formation begins with the filtration of essentially protein free plasma through theglomerular capillaries into Bowman's space. 20% of the water and crystalloid constituents(solute molecules of small size) of the plasma which enters the kidney via the renal artery isfiltered through the glomerular membrane.

There are over one million excretory units called nephrons in each kidney. We canrepresent all the nephrons together in one simple diagram.

GLOMERULUS

Peritubular---- bloodSECRETION - This is the process bywhich substances from theperitubular blood pass into the

tubular fluid.

REABSORPTION - This is the processby which substances from thetubular fluid pass to the surrounding(peritubular) fluid then the peritubularblood." L---;,.

"""."ROXIMAL"and DISTAL -----4:=1TUBULES

FILTRATION180 Iitres/day(125 ml/minute)(NB. Total plasmavolume is about3 lltres, so th isgives some idea ofhow often theplasma has to befiltered andreabsorbedeach day.)

EXCRETION is when substances pass from the1.8 Iitres/day body in the urine.

Note that there are 2 routes for a substance in the blood to be excreted in the urine. 1. Itcan be filtered and not reabsorbed or 2. it can be secreted and not reabsorbed. In bothcases the substances will then be excreted in the urine.The transport mechanisms for reabsorption and secretion are the same as the transport

170 mechanisms in other cells (see pages 60, 61).


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EXC RETORY SYS

FORCES INVOLVED IN FILTRATIOAbout 25% of the left ventricle's total output of blood is distributed through the renalarteries to the kidneys where n It ra tion of 20% of its plasma takes place.

AFFERENT ARTERIOLE EFFERENTARTERIO LE

TheGLOMERULUSAt efferent endof capillary Peffdecreases, main lybecause water isfiltered off andconcentration ofplasma proteins andtherefore osmotic

pressure IncreasesPeff=58 - (35 + 15)= 8mm Hg.About 180 Iitres of dilute

fi ltrate areformed in th is way eachday by the glomeruliof the kidneys.Such filtrate containsglucose, salts, urea,uric acid, potassium,phosphates, sulphates, etc.,in the same proportionsas in blood plasma.

-125 ml f il trate _e...aor deproteinizedplasma per minute .....-- \[WATER, CRYSTALLOIDS . . 0No COLLOIDS OR CELLS] 0are fil tered throughcapillary and t tcapsular membranesintoRENAL TUBULE

eQ

[The figures representthe volume of bloodentering and leavingglomeruli of bothhuman kidneys.]

At AFFERENT end ofcapillary th is resultsin an effectivefiltration pressure (Peff)of 60 - (25 + 15) mmHg= 20 mmHgThis value decreasesas the blood f lowsalong these capillaries

The glomerular membrane acts as a simple nIter - i.e. no energy is used up by the cells infiltration. It has 3 layers: capillary endothelial cells with large pores; a basementmembrane; epithelial cells of Bowman's capsule called podocytes which have octopus-likeextensions or foot processes embedded in the basement membrane.


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XC RETORY SYSTEM

ER REABSORPTION - PROXIMAL TUBULE

Water is not actively reabsorbed by the tubular cells. It s movement is determinedpassively by the osmotic gradient set up by solutes, chiefly by sodium.65% of the water and sodium filtered into Bowman's capsule from the glomerularcapillaries is reabsorbed in the proximal convoluted tubule.Na + moves into the epithelial cells of the proximal tubule, see p. 182. It is then actively

transported into the lateral intercellular spaces by a Na + , K + ATPase pump.

TUBULELUMEN Na+ Na+ TIGHTJUNCTIONS

Na+ LATERALINTERCELLULAR

H20 ... - - - SPACES - - - BASEMENT

PERITUBULAR CAPILLARYTRANSCELLULARPATHWAY

PARACELLULARPATHWAY

Accumulation of Na+ in the lateral intercellular spaces creates an osmotic gradient acrossthe epithelium. This osmotic gradient moves water into the lateral intercellular spaceseither through the cells (i.e. via the transcellular pathway) or across the so-called tightjunctions (i.e. via the paracellular pathway).As fluid accumulates in the intercellular spaces the hydrostatic pressure increases and

forces fluid across the basement membrane into the peritubular capillaries.A similar mechanism exists for concentrating bile in the gall bladder by waterreabsorption and for the reabsorption of water and electrolytes in the intestines.This method of fluid absorption coupling water movement to sodium transport across

tight-junctioned epithelia is called the standing gradient mechanism.


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EXCRETORY SYS

WATER REABSORPTION - DISTAL AND COLLECTINTUBULES -

As tubular fluid movesthrough medulla, watercontinues to move out.Fluid acquires sameosmotic pressure assurrounding interstitialflu id l.e, rises from300 to 1400 mosmollkg H20 .

300mosmol/kg H20

LATEDISTAL TUBULE

(ADH makes cells permeable to H20 )HOi A2 , IH20 moves out " _oJ ' Iand tubular , ' , ' f ' \ " I . .fl

ld b ' , H20, ..... I InterstitialUI ecomes , , I , ' " ftuid300 mosmol/kg " " I 'H 20 130U0 l/k, " I mosmo gH20 ; sam.e as ' " H20 throughoutsurrounding " " k'f ' I I cortex.fluid. , ' , ' H20,' ,' I

_,,",' I I I- - - - - .." 300 I I I, I300 - -+-- - H2 0 , " 300 mosmol/kg H2 0H20 *- - - - -, ,

I I/ I, ,I I, II ,4 , 'I ,, ,

I XI '1400 mosmol/kg H2 0 " r--...... 1400mosmol/kg H2 0HYPERTONIC URINE (1400 mosmol/kg) EXCRETED

CORTICO-MEDULLARYJUNCTION

Water reabsorption in the distal convoluted tubules and the collecting ducts depends on (1)the permeability of the tubules to water, and (2) the osmotic pressure of the interstitialfluid surrounding the tubules.

The function of the EARLY distal convoluted tubule (first two thirds) differs from that ofthe last third, called the LATE distal tubule.

The late distal tubule and the collecting tubules are made permeable to water by thepresence in the circulation of antidiuretic hormone (ADH) released from the posteriorpituitary gland (p . 212). The early distal tubule is not pe rmeab le to water and itspermeability is not changed by ADH.

The osmotic pressure of the interstitial fluid which surrounds the tubules throughoutthe cortex is isosmotic or the clinical term isotonic (300 mosmol /kg H 20 , the same asinside the cells). In the medulla there is a gradient of osmotic pressure in the interstitialfluid. I t increases from 300 mosmol/kg H 20 at the cortico-medullary junction to 1400mosmol /kg H20 at the t ip of the papilla. The gradient is formed by the counter-currentmechanism in the loops of Henle (pp. 175, 176).When ADH is PRESENT in circulation:

EARLYDISTAL TUBULE(Not permeable to water)_...Fluid from Na"ascend inglimb of 300loop of Henle

is hypotonic.Ii: It becomeso more hypotonicu in early tubuleas Na " is 300reabsorbed.

ADH increases intracellular cAMP which causes the insertion of water channels into themembrane of the cells, making them permeable to water. .


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ORY SYSTEM

ER REABSORPTION - DISTAL AND COLLECTING- 2.

Secretion of antidiuretic hormone is inhibited by a decrease in the osmotic pressure ofthe plasma or an increase in circulating blood volume. These are detected respectively byosmoreceptors in the hypothalamus and low pressure receptors in the left atrium.Inhibition of ADH secretion results in the excretion of a greater volume of dilute urine,thus decreasing the body fluid volume and increasing its osmotic pressure.

When ADH is ABSENT from the circulation:EARLYDISTAL TUBULE

(Not permeable to water)

LATEDISTAL TUBULE(Absence of ADH makes cells

impermeable to H20 ) .

As no ADH ispresent, nowater will bereabsorbed anda large volumewill be excreted.

Interstitialfluid300 mosmol/I kg H20throughoutcortex.

Fluid intubule- say100 mosmollkg H20,.-300

Fluid intubule -

say 100 mosmollkg H20I

HYPOTONICURINEEXCRETED

No H20 moves ou tas tube is no tpermeable towater. Fluidin tubuleremains

hypotonic.

300

300 mosmollkg H2 0

1400 mosmollkg H2 0

300

300

CORTICO-MEDULLARY JUNCTION

Fluid fromascending limb ofloop of Henleis hypotonic.It becomesmore hypotonicin early tubuleas Na " isreabsorbed.

xwI -a::ou

:5...J:::>ow:;E

The degree of inhibition of ADH secretion will depend on the osmotic pressure of theplasma or the volume of the plasma. The amount of ADH secreted will be adjusted so thatthe osmotic pressure of the plasma and the blood volume are returned to normal values.


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EXCRETORY SYS

FUNCTION OF THE LOOP OF HENLE -

200

A200

200

200

350--\-,.. H2 035050

350350

D350

----.-

EQUILIB-RATIONBETWEENDESC.lIMBAND ISF200

A200

200

400Na

400Na++-

400Na-4f-

400 20000

D

300

300300

TRANSPORTFROMASCENDINGLIMBTOISF00

300

ASC.LIMB (A)300

30000300300

300300300

T h e function of th e loop of Henle is to form a g r a d i e n t o f osm ot i c p r e s s u r e in th ei n t e r s t i t i a l flu id of th e m e d u l l a of th e kidney. This enables th e f luid in th e collectingtubules to be concentrated as t he t ub ul es run t hr ou gh t he medulla, an d urine, which ish yp e rt o nic t o plasma, to be excreted.

Fluid in th e descending limb of th e loop of H en le r un s in th e opposite direction to (i.e.counter to) th e fluid in th e ascending limb, hence th e mechanism is known as th ec o u n t e r - c u r r e n t m e c h a n i s m for th e concent r at i on of urine.

T he different characteristics of th e two limbs ar e very important an d must ber e me mb er ed in order to und er s ta nd t he mechanism.

T he descending limb is p e r m e a b l e to water bu t n o t p e rm e a b le to solute (especiallyNa + an d C l ) . T h e ascending limb is i m p e r m e a b l e to water but p e r m e a b l e to solute. Inaddition, the fluid is continuously flowing round th e loop.

I t is instruct ive to imagine that this continuous process can occur in separate stages and,to he lp to understand ho w th e gradient is formed, consider what changes in osmoticp ressure would o cc ur i n each separate stage.

Imagine that we can start with all tubular fluid an d interst it ial fluid (ISF) at 300 mosmol{kg H 2 0 .DESC.LIMB (D)300 300

SUPPOSE A LITTLE FLOW OCCURS THEN STOPSt A D A D A300 350 200 300 400 150 350 350 150Na" Na EQU l lIB- H2O300 350 200

TRANSPORT 300 400 150 RATION 350 350 150AGAIN Na AGAIN H2O350 350 350 350 450 250 400 400 250Na H2O 350 350 350 350 450 250 400 400 250FLOW

Further flow would increase the osmotic pressure at th e tip to 400 mosmol jkg H20 . Th egradient in th e interstitial fluid has started to form. I f more values were used i n each limban d th e processes repeated many times over, th e steady state shown on page 176 would bereached.


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CRETORY SYSTEM

OF THE LOOP OF HENLE - 2.As fluid moves down th e descending limb of the loop of Henle, w a t e r moves o u tbecause th e surrounding interstit ial f luid is at a.higher osmotic pressure. With maximumconcentration the osmotic pressure of the fluid at t he b en d of the loop can reach1400 mosmol/kg H 20 . As fluid flows up th e ascendi ng limb, solute, especially Na + an dcr, m oves o u t into th e interstitial fluid and, since th e ascending limb is i m p e r m e a b l e towater, water does not follow th e solute an d the fluid passing on to th e distal convolutedtubule is hypotonic.Values of th e osmotic pressure, with maximum concentration, when the steady state isreached:

DESCENDINGLIMBASCENDINGLIMB COLLECTINGDUCT

300

600

1200

900

1400

URINEINTO PELVIS

OF KIDNEY

300NaCI

1400

700

400

100

1000

NaCI

NaCI

NaCI

1400

Not permeableto water

1200

[UNITS are mosmol/kg H20 .]

300

900

600

1400

1200

900

300

600

The site of f inal concentration is in th e collecting duct s which ru n through themedulla to th e tips of the papillae. I f AD H is present, water diffuses ou t of th e collectingduct fluid into th e interstitial fluid. T h e result is that th e fluid at th e en d of the collectingduct is equilibrated with th e interstitial fluid at th e tip of th e papillae an d is hypertonic.I t passes into the pelvis of th e kidney as hypertonic ur i ne.


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EXCRETORY SY

ROLE OF UREA IN THE COUNTER-CURRENT MECHANIS

T h e gradient of osmotic pressure in th e interstitial flu id o f th e medulla of the kidney isnot due solely to Na + an d C r. At th e tips of th e papillae a bo ut 5 0% of th e osmoticpressure is du e to u r e a .

The distal tubule,the cortical andouter medullarycollecting tubulesare NOT permeabto urea. Sincewater is reabsorbethere, theconcentrationof urea rises.----

-. -- -

UREA

COLLECTINGDUCT

H20_________ UREA

NaCI-r'J-.-NaCI

UREA

- - - -

H20 NaCI- - - - UREA - - - - - - - - - -

DISTALCONVOLUTEDTUBULE \ \ \...---....

NaCI

--- - -- ---4

- - - - - - -CORTEX

OUTERMEDULLA

Fluid in proximaltubule remains isotornc sinceH20 and NaCI arereabsorbed atequivalent rates.

When urea reachesthe inner medullarycollecting tubuleits concentrationhas risen to a h ighlevel. Th is portionof the tubule ispermeable to ureaand it diffuses outinto the interstitialfluid of the medulla.

UREA

UREA

UREANaCI

Some urea diffusesinto the descendingand ascending limbsof the loop of Henle.

INNERMEDULLA

The osmoticpressure of 1400mosmollkgH20 in the tubuleis almostentirely due toNaCI. - - - - -- . . tNaCI

It-\ \, LOOP OF HENLEAt th e bend of th e loop of Henle th e osmotic pressure in th e tubule is the same as th at of

the su rrounding in terstitial fluid, 1400 mosmol/kg H 20 . Bu t, since inside th e tubule th eosmotic pr essure is practically all du e to NaCI and in the surrounding interstitial fluid it isonly 50% du e to NaCI, there is a large NaCI concentration gradient. Hence, as the tubularfluid goes up th e thin ascending limb, which is permeable to NaCI, NaCI diffuses passivelyou t of th e tubule into the interstitial fluid an d contributes to th e osmotic pressure of th einterstitial fluid in the inner medulla.


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ORY SYSTEM

OF THE VASA RECTA

Creating the osmotic gradient in the medulla of the kidney and producing urine hypertonicto plasma involve the reabsorption into the medullary interstitial fluid of sodium, chloride,urea and water. Accumulation of excess quantities of these substances in the medulla isprevented by their removal into the blood stream by the vasa recta . These capillariesfrom the efferent arteriole of the juxtamedullary glomeruli have an ascending limb, adescending limb and a hairpin bend.

Arcuateartery,,,f ferent - -- ./ farteriole Juxta-medullaryglomerulus < ;

..... ...

- - - - - - - - - ' .. Arcuate vein........ ..

Blood at thebeginning of thedescending l imb hasan osmolality of300 mosmol/kg H 20 .As i t descends intothe medulla, NaCIand urea move intothe capillaries bydiffusion, watermoves out and theosmolality increases.

Descending -vasa recta

NaCI . . . . .

- - Ascendingvasa recta

After the bend, theblood flows up theascending l imb andsolute and watermove in the oppositedirection. NaCI andurea move out andwater moves into thecapillaries. Thecapillary loop is saidto act as a counter-current exchanger.

In fact, not all the NaCI and urea that enters the descending limb comes out theascending limb and more water goes into the ascending limb than leaves the descendinglimb. The blood that empties into the arcuate vein is sl ightly hypertonic and its volume isgreater than that of the blood which comes into the descending l imb from the efferentarteriole. About 10 m1 of blood per minute with an osmolality of 300 mosmol/kg H 20enter the descending capillary and II ml of blood per minute with an osmolality of325 mosmol/kg H 20 flow from the ascending limb into the arcuate veins. The solute andwater reabsorbed into the medullary interstitial fluid are thus returned to the circulation

8 and a steady state is maintained in the medulla of the kidney.


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EXCRETORY SYS

MAINTENANCE OF ACI D- BASE B A L A N C EAn acid is a substance which liberates H + ions (proton donor). A base is a substance whichcan accept a H + ion (p roton acceptor). Acids are formed in the body during thebreakdown of food) during cell metabolism and) especially) by the production of CO2 andits combination with water. However the concentration of free H + in the body fluids iskept relatively constant at about pH 7.4 (pH 7.4 = 4 x 10-8 mol/litre of H +).This equilibrium is maintained by buffer systems binding free H +; by the lungs

eliminating CO 2 and finally by the kidneys excreting H + and conserving base (mainlyHC03- ) .The main extracellular fluid buffer system is the bicarbonate buffer systemCO 2+H 20 H 2C 0 3 H + + HC03- . Thus i fH + is libera ted i t combines with HC03- )forming carbonic acid which breaks down to CO 2 + H 2 0 . NB: HC0 3- is 'used up ' in thisreaction .The Henderson-Hasselbalch equation shows the relationship between pl-l, CO2 and HC0 3-

H ex: Concentration o f HCOip Dissolved CO 2The lungs decrease H + (increase pH) by eliminating CO 2 in expired ai r.The kidneys decrease H + (increase pH) by reabsorption ofHC03- and by excretion of H +.CONSERVATION OF BASE

NB: brushborder

BLOOD

H+HC 03

tH2C03 ...CO 2+H20

FILTRATE

Secreted hydrogen ions reactwith bicarbonate to form __ ---arbon acid. - _ _This carbonic acid breaks d ow n t oform CO 2 and H2 0 . Reaction isin cell membrane o f proximal - - -tubule.

Secretion o f free hydrogen ions counter-transported with sodium ions(secondary active transport) -- - - ......

REABSORPTION OF B/CARBONATEBicarbonate is in a concentrationo f about 24 mmol/1 in fil trate. Mostis reabsorbed in the proximal tubuleby this mechanism - _ _ - -

This mechanism reabsorbs base (HC03-)


16/28

RY SYSTEM

OF ACID-BASE BALANCE - 2To maintain the body fluids at a constant pH, the same quantity of hydrogen ion that isingested in the diet must be excreted. In addition, the body must be capable of alteringthe H + excretion in response to changes in I i + production and to compensate for anygastrointestinal loss or gain resulting from disease e.g. by vomiting.

The cells of the proximal, late distal convoluted tubule and cortical collecting tubules ofthe kidney all secrete H + into the tubules. There are 2 mechanisms:In the PROXIMAL TUBULE TUBULE CELL

PERITUBULARFLUID

carbonicanhydraseCA

H2C03/ -,W + HC03 _-+---'

TUBULELUMENH + is made available by thespeedy combination of H2 0and CO 2 in the presence ofthe enzyme carbonicanhydrase. The H 2C 0 3 soformed dissociates into H +and HC03- . The latter isreabsorbed. H + ions arecounter-transported withNa + and secreted into thetubular lumen.

PERITUBULARFLUIDCA

CELL

" ,ATP

LUMENH + ions are made availablein a similar way and are thensecreted into the lumen ofthe tubules by active, ATPdriven pumps called protonpumps.

In the LATE DISTALTUBULE AND CORTICALCOLLECTING DUCTS

The epithelium of the collecting ducts is made up of principal cells (P cells) andintercalated cells (I cells). I cells are also present in the late distal tubules. The protonpumps are located in the I cells which also contain abundant carbonic anhydrase.

In acidosis (excess H + in the body) the number of proton pumps in the membraneIncreases.


17/28

EXC RETORY SYS

MAINTENANCE OF ACID-BASE BALANCEA large increase in concentration of free H+ in the tubular filtrate (to pH 4.5) wouldprevent the secretion of H + ions from the tubular cells. Two mechanisms bind free H + inthe filtrate and allow continued secretion of H + .

BLOOD

(

BLOOD

EPITHELIUMOF TUBULEMAINLY DISTALH20 + CO2 ..... . . . - : ---- CO2Carbonic

anhydrase Reabsorptionenzvrne ofH2C03\ base ,H: HC03- HC03-Nat

FILTRATE

URINEW EXCRETION

Secreted hydrogen ion isbound and excreted as - - -- -- ..-.. ---monobasic phosphate. -

PHOSPHATE MECHANISM

This mechanism excretes H+and reabsorbs some base (HC0 31.

Hydrogen ion is secretedeither counter-transported with Na+ - - - - - ..., ,or by primary active transport - ' , " ,(proton pump).

Dibasic phosphatein fi l trate - - - - - _---- --- ----

r-----;- NH3 formed as NH4+ fromglutamine in proximaltubule cells. Passes intoproximal t ubule -reabsorbed in loop ofHenle into medullarylnterstitial'fluid.Diffuses from there as NH3into collecting tubule.

EPITHELIUM OF BLOODCOLLECTINGTUBULEH2 0 + CO 2 4 CO 2ICarbonic It anhydrase ReabsorptionH2C03 enzyme ofmore base

lfR " "+- - - - '

FILTRATE

URINEW EXCRETION

Hydrogen ion is secreted , ,by a proton pump: -'. , ' . Secreted H+ combines with - {.- H+ammonia (NH3) which +iffuses from the tubular cell- __NH3 4- -- +Thus an ammonium ion (NH4+)is formed. NH/Ce ll membrane is permeable toNH3 but not to NH4+so NH4+containing secreted H+ is excreted.

This is the most importantmechanism fo r buffering Win tubule.

AMMONIA MECHANISM

This mechanism excretes H+and reabsorbs some base (HC03- ).


18/28

ETORY SYSTEM

REABSORPTION

More than 99% of the sodium filtered from the glomerular capillaries of the kidneys isreabsorbed as the tubular fluid passes along the nephron. I ts reabsorption is dependenton the active transport by a Na+, K + A mechanism which pumps Na + from thebasolateral membrane of the tubular cells into the peritubular fluid. The intracellularconcentration of sodium is thus kept low. Since, in the tubular fluid, its concentration ishigh, Na + moves across the apical membrane into the cell down the electrochemicalgradient.Na + REABSORPTION

DISTAL TUBULES ANDCOLLECTING DUCTSReabsorb about 10% of thefiltered Na+ .-

LOOP OF HENLEII Reabsorbs about 25% of

I the filtered Na + The'thick ascending limb ofHenle's loop is particularlyimportant for Na+reabsorption whichoccurs by cotransportwith 2Cr and IK +(a INa+, 2Cr, IK +symporter). It is alsocountertransportedwith H +.

The early distal tubule. .. cotransports Na + with cr., The late distal tubule

....

' . / and collecting ducts;' /' reabsorb Na + by its'" diffusion through water-filled channels of the

principal cells, drivenby their internalnegative potential.

--.

-

,

' .

.-

- - -

-- . !" r .

In the second half of .-the tubule, the high cr ". ,-concentranon enables ,-it to diffuse passivelythrough tight junctionsto the lateral intercellularspaces, making the basalside of the cell negativelycharged with respect tothe tubular fluid side, soNa + follows cr acrossthe tight junctions intothe intracellular spacesalong the electrical gradient.Na + is also reabsorbed bythe transcellular route,countertransported with H +.

In the proximal tubule, 65% of both the filtered Na + and water are reabsorbed, hencethe osmolality of the fluid leaving the proximal tubule to enter the loop of Henle isvirtually the same as that of plasma.

PROXIMAL TUBULEReabsorbs about 65% ofthe filtered Na + .In first half of tubule,Na + is reabsorbed bycotransport with bicarbonate,glucose, amino acids, phosphate 'and lactate. "Water fol lows the Na+ and,since little cr is reabsorbedhere, its concentration rises.


19/28

EXCRETORY SYS

DEFENCE OF BODY FLUID VOLUM

The volume of the extracellular fluid (ECF) is determined mainly by the amount ofosmotically active solute it contains. Na + is the most important active solute in the body,hence mechanisms that control Na + balance will also control ECF volume.

Hencedecreasglomerufi ltratiorate

Decreasesfi lteredexcr

KIDNEY

DECREASED Na" INTAKEcauses excretion of water

DECREASESBLOOD VOLUME+LOWER PRESSUREdetected by - - - - - Afferent Carotid andarteriole Aortic baro-receptorsti All sympathenerve fi ring(including re

sympatheticnerv+ConstrrenaarterioReleasesadreno-cortical

Releasesrerun

StimulatesThirstConstricts

blood vesselsStimulatesADH release

.

Increasedreabsorption of : ' sodium . ;

Collectingducts becomepermeableto water

ALDOSTERONE

ANGIOTENSIN II

BLOOD

ANGlO-TENSINOGENANGIOTENSIN Iconvertmg

enzyme inlungs

Collectingducts becomeimpermeableto water

Decreasedreabsorptionof water

KIDNEY

ReflexlyinhibitsADHrelease

,,

, ,

. ,, .

, ..""'" .

INCREASESBLOODVOLUMEt stretchesAtria ofHeart

ReleasesAtrialNatriureticPeptide(ANP)IncreasesNa"excretion

INCREASED Na+ INTAKEcauses retention of water

Increased Na" and H20 Decreased Na" andExcretion H2 0 ExcretionRestores body fluid volume Restores body f lu id volumeControl of vasopressin (ADH) release by changes in volume overrides its contro l by

osmo tic changes.


20/28

RY SYSTEM

REGULATION OF POTASSIUM EXCRETION

If subject is potassiumdepleted - REABSORB

potasstum.If intake is normal orincreased - SECRETE

potassium .

DISTAL AND COLLECTINGTUBULES- ' \,,,

'\ ,

,-

,

,

V: .', ',,,, .

- , ,

,.'

PROXIMAL TUBULEreabsorbs about -... ,65% of filtered ....... ..... / :'potassium . " i. -. . .. '. . '- ... ' : ., ., ., .

LOOP OF HENLEreabsorbs about20% of filteredpotassium

About 85% of the potassium that is filtered by the kidney nephron is r e a b s o r b e dregardless of the state of potassium balance of the subject, Regulation of excretion is,mainly contro lled by altering potassiu m secr et i on by th e distal t ub ul es a nd collectingducts.

T he commonest regulatory mechanism occurs when the intake is normal ,

: : I J. 7 ,., . , .

-,

,,

"

Tubu lar secretion producesincreased excretion

Increases intracellular K+of principal cells of tubules __-nd thus increases _ -----ecretion from _ - - - __. , , ' - - - -them. _ . , - --- ,-o r ,-- ,;,", " Increases cell Na+, K+ ATPase" which raises" intracellular K+ of

/ tubular cells and/ increases K+secretion.

-,,,,,/ALDOSTERONE

; t,,,,,,Releases"Aldosterone

BLOODPLASMA+

Nonnal or increasedintake of K in d ie traisesplasma K+

directlystimulates ,

aldosterone /secretion ,I,,..,., I

AD H, flow rate of tubular fluid, acid-base balance, a nd t ub ul ar fluid Na + concentrationalso mo dify K + secre tion but are much less important than al dost er one an d p l a s m a K +concent r at i on .


21/28

EXCRETORY SYST

DEFENCE OF BODY FLUID TONICIT

The tonic ity or osmolality of body fluids is controlled by THIRST which alters waterintake, and VASOPRESSIN (antidiuretic hormone, ADH) released from the posteriorpituitary gland (page 214) which alters water output by the kidney.

THIRST

Increasedwaterintake

DILUTION OF BODYFLUIDS

.- .

. ..: lb.. WATERj . ."" RETENTION

. "" .

: KIDNEY. . /; t lIncreases permeabilityto water of the distal

: Increased tubular. : \ . reabsor tion of water .J:

".

!, .

POSTERIOR PITUITARY..... '. discharges ADH to." .". blood stream

TISSUE FLUIDCONCENTRATEDMovement of H20OSMOTIC from area of low

PRESSURE OP to area ofincreasedY higher OP\,. I . . OSMORECEPTORS ANTERIOR':"""" stimulated HYPOTHALAMU SUPRA-OPTIC 4 (centre in Brai ..;. , .. u- NUCLEUS and->"evel ofADHin b loodrises

DRY /'I"'" Sensory nerves from mouth and pharynx ------- - . .MOUTHI

01 INISHEDSALIVARY BLOOD INTRACELLULAR FLUID CONCEN- CONCENTRATED \ .....- : ---Al l cells share this...... J


22/28

RETORY SYSTEM

CLEARANCE

The plasma clearance of a substance can be defined in 2 ways. (1) I t is the volume ofplasma (in ml) cleared of a given substance per minute by the kidney or (2) it is thevolume of plasma (in ml) which contained the amount of the substance which isexcreted in the urine in one minute.Consider three hypothetical substances, all of which are filtered. 'A ' is a substancewhich is neither reabsorbed nor secreted by the kidney tubules, 'B ' is a substancesome of which is reabsorbed but none secreted, and 'C' is a substance none of whichis reabsorbed but some is secreted by the tubules.

VPP +

Since A is not reabsorbed or secreted, _ + _ of Awill appear in the urine per minute.

Let VP contain _ amount of substance A.Let VP contain 0 amount of substance B.Let VP contain [111 amount of substance C.Suppose 2 x VP ml is filteredper minute i.e, theglomerular filtration rate =Hence the amounts of each substance going into thetubular f luid each minute will be:A = _ + _ B = 0 + -;;. L and C = IT . + I!mB

Let this rectangle 'VP' represent a volume VPin ml of plasma.

-.,c

-_oB 0 ,:""'"""""'

AmountInurinel

min.VP VP

+..

The plasma clearance i.e. the amount of plasmain which _ + _ was contained will be L_-- I

VP

Some of substance B is reabsorbed. Let us say 0 amount/min.Hence 0 will appear in the urine per minute.The plasma clearance of B will be ----- - -------- I - - . .JSome of substance C is secreted. Let us say g amount/min,Hence _ +1M + will appear in the urine per minute.The plasma clearance of C will be VP + VP + VP

A substance which is neither reabsorbed from nor secreted into the tubules, like inulin,will have a clearance value equal to the glomerular filtration rate.A substance which is reabsorbed into the blood again, like urea, will have a clearancevalue less than the glomerular filtration rate.A substance which is secreted into the tubular fluid from the peritubular blood, likePAH, will have a clearance value greater than the glomerular filtration rate.


23/28

EXCRETORY SYS

THE 'CLEARANCE' OF INULIN IN THE NEPHRO

The ra te of glomerular filtration (GFR) can be found by measuring the 'plasma clearance'of a substance like substance 'A' on page 186 which is filtered by the renal corpuscle bu tneither reabsorbed nor secreted by the tubular epithelium. Inulin and creatinine are suchsubstances. The use of inulin is more accurate but the technique using creatinine issimpler.

UVP

By 'plasma clearance'is meant the volume ofplasma which containedthe amount of thesubstance which isexcreted in the urinein 1 minute.

CALCULATfONPlasma contained50 mg inulin/100 ml (P)Ur ine contained6250 mg inulin/100 ml (U)

Urine excreted at rate of1 ml/m inute (V).'. inulin clearance orglomerular filtration

t 6250 x 1 .ra e = 50 r.e.= 125 mi/minute

I

..

Inulin

I

T his idea of clearance can be applied to other substances naturally present such as urea,or artificially introduced, such as diodone .


24/28

EXCRETORY SYSTEM

UREA 'CLEARANCE'

Urea, like inulin, is fil tered by the renal corpuscle. Unlike inulin some urea is reabsorbedback into the blood stream from the tubules . See substance 'B' on page 186.

Plasma contained30 mg urea/100 ml (PIUrine contained2000 mg urea/100 ml (UIUrine excreted at rate of1 mllminute (VI

. , Volume of plasmacleared of urea bynormal kidney in oneminute = 2000 x 1 . UV30 I.e. P= 66.7 ml /m inute.Le. urea clearance.

I

I

-

- \ -Urea

20 mg

Water-\) -

Glomerular filtrate125 mllm inuteUrea 30 mg/100 ml(i.e, 37.5 mg/minl

f. .-oj -- -e P-_() IJ- -c 1 ml

,

- ---....,..- --_ ....... Urine

1 m l/minute20 mg urea/ml(or 2000 mg/100 mil

Plasmaleaving kidney659 mllm inutewith 178 mg (160.5 + 17.51 mgUrea/minute

Urea clearance is used as a test of renal function.

188


25/28

EXC RETORY SYS

PAH 'CLEARANCCertain special substances are filtered by the renal corpuscle and the rest that escapesfiltration is then secreted totally from the peritubular blood into the tubule. Thus the renalartery contains the substance bu t the renal vein contains none. Para-aminohippuricacid (PAH) and diodone are such substances. The 'Plasma Clearance' of these substancesmeasures the renal plasma flow rate. Compare this with substance 'C ' on page 186.

The renalblood flow canbe calculated fromthe renal plasmaflow by firstmeasuring theproportion of RBCto plasma in theblood (theHAEMATOCRIT)

,

,

..

10.7 mgPAH-

Plasma leaving

; ; ; :-


26/28

Y SYSTEM

URINARY BLADDER AND URETERS

A resistant, distensible transitional epithelium lines all ur inary passages.

conveys urine toextenor.

acts as reservoir fo rurine.[Size and posit ion varywith amount of ur ine stored(120-320 cc).]

- Smooth muscle coats -distend as ur ine collects;contract periodical ly toexpel urine to urethra.

!,,Js-- Ii - ---. t

- - _ _ _ _ _ _ convey urine fromkidneys to bladder.,",- Smooth muscle coats - slow

waves of contraction(every 10 seconds) propelurine along ureter.1-5 small 'spurts' enterbladder per minute.

Circular striated muscle (undervo luntary control - central nervoussystem)

---

,!

----...---RETHRA .--:..-- - - - - - --- - - - - - - - - --- - - -- - - -

Membranous tube

,

URETERS - - - - - - - - - - -Long, narrowmusculartubeswith outerfibrous tissue " ,coat and .....Inner mucousmembrane

BLADDER - - - - - -Hollowmuscularorgan ...

...... ,

...,...


27/28

EXCRETORY SYST

STORAGE AND EXPULSION OF URIN

Urine is formed continuously by the kidneys. It collects, drop by drop, in the urinarybladder which expands to hold about 300 ml. When the bladder is full the desire to voidurine is experienced.

In adul t-the ref lex can becontrolled andinhibited

voluntarilythroughHIGHERCENTRESI

IIII

234

LUMBAR 123

SACRAL

Sensationsto- consciousnessIIII

,\\\\\MIDBRAINPONSIIIIII

reflexmechanismcan berestrainedIIIIIIReflexcontractions of bladderwall can be inhibited;contractions of sphinctercan be induced voluntarily.

//When restrain t is removed'sensory afferents are allowedto activate parasympathetic-- - efferents and bladder contracts

(As bladder distends,walls of ureter arepressed togetherpreventingregurgitation of urine.)

PARASYMPATHETICEfferents

Constrict blood vessels_V SYMPATHETIC... Efferents . " ,, ,'Inhibits ganglia I

..".".,-" Afferents (

EFFERENT PATHWAYSMotor impulses inPARASYMPATHETICma y be inhibitedby impulses inSYMPATHETICImpulses in motor

somatic nervescan controlexternal sphincter(sympathetic efferents constrict blood vessels andinh ibit parasympathetic ganglia).

r-.....: r-;! :/ .) \

External sphincterrelaxes

MICTURITION is essentially reflex -carried o u t t hr ou gh centres in spinal cord

EFFECT - - - - - URINEVOIDED

EFFECTORSSmooth musclein BLADDER WALLand URETHRAcontract, openingvesical or ifice

STIMULUSDistension ofreceptors in ----_ _ AFFERENTPATHWAYSsmooth muscle

/ '"1"A \I ...I When empty,\ pressure in bladder is zeroWhen 50 ml urine collect -+ pressure T to 10 cm H20 . Up to 300 or 400 ml -+ little\ increase in pressure., Thereafter pressure in" bladder rises steeply

" -+ stretch


28/28

EXCRETORY SYSTEM

URINE

VOLUME: In adult1000-1500 ml/24 hoursSPECIFICGRAVITY:

1.010-1.035

Vary with fluid intake and withfluid output from other routes -skin, lungs, gut .[Volume reduced during sleep andmuscular exercise:specific gravity greater on proteindiet.]

REACTION: Usually sl ightly acid -(pH 4.5-8)

Varies with diet[acid on ordinary mixed diet:alkaline on vegetarian diet].

COMPOSITIONWater --- 1000-1500 ml /24 h

Urea ----------- 400 --derived from breakdown of protein -therefore varies with protein in diet.Uric Acid - - ------ 4 --comes from purine of food and body

tissues.Creatinine ------- 10 --from breakdown of body tissues;uninfluenced by amount of dietary protein.Ammonia - - - - - - - - 40 - - formed in kidney from glutamine

brought to it by blood stream;varies with amounts of acid substancesrequiring neutralization in the kidney.

millimolesexcreted in 24 h

[These figures areapproximate andvary widely in healthyindividuals]

Sodium -------- 200Chloride-------- 200Calcium ---------- 5Potassium ------- 50Phosphates ------ 25Sulphates-------- 50Organicsubstances

Inorganicsubstances

ODOUR:Aromatic

when fresh -+ammoniacalon standingdue tobacterialdecomposition

of urea to

COLOUR:Yellow due tourochrome

pigment -probably fromdestruction of tissue protem.

Moreconcentrated

and darker inearly morning- less waterexcreted atnight but

unchangedamounts of

urinary solids.

ammoma .

Documents

PHYSIO Notes - Renal