potential test 3 questions.docx

8/17/2019 Potential test 3 questions.docx

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Potential Questions for TEST 3: If they are in bold --- take a 2nd and 3rd look at them.

KIDNEY;

1. Describe glomerular filtration and how it works, tubular reabsorption a

purpose, and tubular secretion and its purpose.

Urine formation involves three ro!esses" glomerular filtration, tubular reabsorptio

tubular secretion

Urinary e#!retion $ %lomerular filtration & tubular se!retion ' tubular reabsortion

()*+E,U), I)T,TI*/:

01 )4 day5 1-2.6) be!ome urine

27 is filtered durin% glomerular filtration.

8lood enters the kidney via the renal arter!.

The diameter of the afferent 0in!omin%5 arteriole is %reater than the diameter of the efferent ar

and hen!e the ressure of the blood inside the %lomerulus.

9ater and solutes of relative mole!ular mass less than " form the filtrate

The %lomerular filtrate enterin% the !asule !ontains ;ater" %lu!ose" amino a!ids" urea" uri

!reatine" !reatinine" /a"


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TU8U), ,E8S*,PTI*/:

)iid soluble to#i!ants are reabsorbed durin% tubular reabsorption> olar !hemi!als and io

e#!reted.

or the most art it o!!urs in the ro#imal !onvoluted tubule.

*nly about 17 of the %lomerular fitrate a!tually leaves the body be!ause the rest 0the other??75 is reabsorbed into the blood ;hile it asses throu%h the renal tubules and du!ts by

"smosis" Diffusion" and #cti$e %ransport.

In &'%

9ater is reabsorbed in the P


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(oop of )enle

@es!endin% )imb of )oo of Aenle

The eithelium linin% of the des!endin% limb of Aenle is relatively permeable to water - but

much much less permeable to the salts Na+ and Cl - , and to urea. Therefore ;ater %radually

moves from the des!endin% limb and into the interstitium

Thin s!endin% )imb of )oo of Aenle

it is impermeable to water, but is highly permeable to Na+ and Cl - , and somewhat permeable t

urea. Therefore /a& and


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@urin% the late sta%es of /a& ion reabsortion in the P


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2. 9hat are and 8 !ellsG Ao; do they ;orkG Ao; do transort systems

eliminate sodium in the kidneyG 9hy is the transort of a!ids and bases

imortant in kidney and sometimes bladder to#i!ityG

and 8 !ells in the distal !onvoluted tubule !an hel modulate the bodyHs A by

sele!tively eliminatin% a!ids or bases and are tyes of inter!alated !ells 0!uboidal !ells

;ith abundant mi!rovilli"5 .

The inter!alated !ells !an be subdivided based on:

%!pe of cell *ecretes +eabsorbs

-

inter!alated

!ells

a!id 0via an ai!al A& -

TPase and A& 4=& e#!han%er 5 in

the form of hydro%en ions

bi!arbonate 0via band 3" a

basolateral


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-tye:

• Turned on ;hen the blood is too a!idi!

•


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Sodium:

• Uses /a-A antiort" /a-%lu!ose symort"sodium ion !hannels

• lmost eliminated in %lomerular filteration

• The kidneys also have a re%ulated me!hanism for reabsorbin% sodium in the distal

nehron.

This me!hanism is !ontrolled by aldosterone" a steroid hormone rodu!ed by the

adrenal !orte#.

ldosterone romotes the e#!retion of otassium ions and the reabsortion of

sodium ions.

https://en.wikipedia.org/wiki/Sodium-hydrogen_antiporterhttps://en.wikipedia.org/wiki/Sodium_ion_channelhttps://en.wikipedia.org/wiki/Sodium-hydrogen_antiporterhttps://en.wikipedia.org/wiki/Sodium_ion_channel


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The release of ldosterone is initiated by the kidneys.

The reabsortion of sodium ions is follo;ed by the reasortion of ;ater.

This !auses blood ressure as ;ell as blood volume to in!rease.

• ,eabsorbtion

P


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3. The !ehalosorin" !ehalosoridine" a!!umulates in the renal !orte#. 9hyG


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+e!hanisms underlyin% !ehalosorine nehroto#i!ity:

t the !ellular level" the me!hanism of !ehalosorine to#i!ity is based on !on!entrative

utake of the dru% into ro#imal tubular eithelia in the kidney !orte#.

Se!i!ally" !ehaloridine is raidly transorted a!ross the basolateral membrane via the

or%ani! anion transorter" *T1.

The transort at the ai!al side is less ;ell !hara!teriNed" but it is !lear that the movement

of !ehaloridine a!ross the !ell-to-tubular lumen membrane is %reatly restri!ted" robablydue to the !ationi! %rou ;ithin the same mole!ule" leadin% to a !onsiderable intra!ellular

a!!umulation of the dru%.

In !ontrast" the anioni! !ehalothin mole!ule raidly moves a!ross the eithelia from the

blood into urine.


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urther do;nstream" at the mole!ular level" the to#i!ity of !ehalosorins has multile

!auses.

These in!lude redo# !y!lin% of the yridine rin% 0see se!tion 6.1.15" a!ylation and

ina!tivation of tubular !ell roteins throu%h the sontaneous rea!tivity of the M-la!tamrin% 0see se!tion 1.35" and inhibition of mito!hondrial fatty a!yl !arnitine transort 0see

se!tion 16.15.

3. 4ercur! and h!dro5uinone are highl! to6ic to the kidne! for the same

reason. 7hat is it8 Describe how the! are acti$ated in detail. During

what process are the! absorbed and thus cause to6icit!8

+er!ury: %lutathione !on%u%ates are metaboliNed by %amma-%lutamyltransetidase

0%-(T5 and dietidase 0@PP5 than reabsorbed. 67 of mer!ury is found in kidney

;ithin a !oule of hours of intake

The kidneys are the rimary tar%et or%ans for a!!umulation of A%2" and the S3

se%ment of the ro#imal tubule is the initial site of to#i!ity.

s the dose or duration of treatment in!reases" the S1 and S2 se%ments may be

affe!ted.

,enal utake of A%2 is very raid ;ith as mu!h as 6 er!ent of a nonto#i! dose of

A%2 found in the kidneys ;ithin a fe; hours of e#osure.


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AydroDuinone: !tivation in kidney by %lutamyl transetidase and dietidase


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8enNohydroDuinone is an intermediate used in the !hemi!al industry and a metabolite

of benNene" and it also o!!urs naturally in !i%arette smoke.

8enNohydroDuinone is nehroto#i! and also indu!es renal tubular adenomas

+e!hanisms of benNohydroDuinone'%lutathione-S-!onRu%ate nehroto#i!ity:


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ollo;in% o#idation of the benNohydroDuinone to the benNoDuinone" this latter is

!onRu%ated to (SA.

This !an o!!ur as a multiste ro!ess" leadin% from the monosubstituted !onRu%ate to

the di-" tri- and even tetra-(S !onRu%ate.

(enerally" (S !onRu%ation has been !onsidered a !ytorote!tive ste be!ause (SA

fun!tions as a sa!ri!ialH nu!leohile sarin% other" more !riti!al !ellular thiol %rous

from irreversible dama%e.

Ao;ever" the multisubstituted (S-!onRu%ates e#hibit differential to#i!ity> ;hile the

mono- and the tetra-(S-!onRu%ates are essentially nonto#i!" the di-(S-!onRu%ate

isomers sho; intermediate to#i!ity" and the 2"3"6-0tri%lutathionylS-yl5 hydroDuinone

e#hibits the hi%hest to#i!ity in the kidney.

These multi-(SA substituted !onRu%ates are a!tively transorted from liver into bile.

fter reabsortion from the %ut" the (S-!onRu%ates rea!h the kidney" ;here they !ome

into !onta!t ;ith the luminal side of the tubular eithelial !ells.

This ole of the !ell is ri!h in t;o etidases ;hi!h seDuentially !leave t;o amino

a!ids off the (S moiety> rst" -%lutamyl transetidase 0(T5" ;hi!h !leaves off the

%lutamate residue" and then dietidase 0@PP5" ;hi!h !atalyNes the removal of

%ly!ine. s a result" the !ysteine !onRu%ate is left behind.

This !ysteine !onRu%ate is readily taken u by the amino a!id transorter into the

ro#imal tubular eithelia.

Inside the !ell" the !ysteine !onRu%ate is o#idiNed to the substituted benNoDuinone.

Quinones" in!ludin% benNoDuinone" are rea!tive se!ies be!ause they are ele!trohiles

;hi!h !an !ovalently bind to nu!leohili! sites of tar%et !omounds" but also be!ause

they !an under%o redo# !y!lin% durin% the redu!tion4o#idation !y!le from the

semiDuinone to the Duinone 0see se!tion 6.1.15.

The 0multi5-!ysteineS-!onRu%ates of benNoDuinone retain this mole!ular !hara!teristi!

of the arent !omound.


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Thus" the key me!hanism underlyin% the nehroto#i!ity of benNohydroDuinone and

other olyhenols is the transort and delivery to the kidney as a result of

(S!onRu%ation.

*n!e in the kidney" the (S-!onRu%ates are metaboli!ally de%raded and a!!umulate in

the tubular !ells 0see i%ure F.15.

6. Ae#a!hlorobutadiene to#i!ity is a !lassi!ial e#amle of liver metabolism

!ausin% to#ity in another or%an 0kidney5. 9hat is the me!hanism by ;hi!h

he#o!hlorobutadiene !auses kidney to#i!ityG Ao; are the (STs involvedG

9hat is -lyase and ho; is it involvedG

Ae#a!hlorobutadiene is an undesired but unavoidable industrial by-rodu!t that arises

durin% the manufa!turin% of !hlorinated hydro!arbons.

The !omound is also released into the environment and a!!umulates in fresh;ater and

marine or%anisms" and it is a ersistent ollutant.

Ae#a!hlorobutadiene is minimally heatoto#i!" but it is a !lassi!al and dosedeendent

nehroto#i!ant in mi!e and rats" dama%in% the S2-se%ment of the ro#imal tubule.

t the ai!al membrane of the tubular !ells" the enta!hlorobutadiene'S-%lutathione

!onRu%ate is de%raded enNymati!ally to enta!hlorobutadiene-S-!ysteine.

This latter !omound is taken u into the !ells throu%h the amino a!id transorter

system.

In the !ell" the !ysteine !onRu%ate !an either be /-a!etylated and e#!reted 0deto#i!ation

ste5" or else bioa!tivated by M-lyase.

+e!hanisms of M-lyase-mediated he#a!hlorobutadiene nehroto#i!ity:


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The !ysteine-S-!onRu%ate of enta!hlorobutadiene 0derived from its %lutathione-

S!onRu%ate5 is a substrate for the enNyme M-lyase.

The !leava%e of the thioether bond results in the %eneration of a nehroto#i! metabolite

;hi!h !an !ause !ovalent bindin% to ma!romole!ules and to#i!ity.

%ain" or%an sele!tivity is determined by the interor%an transort of the %lutathione-

!onRu%ate and the raid a!!umulation and bioa!tivation in the ro#imal tubular eithelia

of the kidney

Its (SA-!onRu%ate is bioa!tivated by a b-lyase in the kidney" or deto#ified by /T.

potential test 3 questions.docx

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