kishore slides

7/21/2019 Kishore Slides

http://slidepdf.com/reader/full/kishore-slides 1/26

Kidney Function:Kidney Function:

What Can We Learn From Operations?What Can We Learn From Operations?

B. K. Kishore, M.D., Ph.D., MBAB. K. Kishore, M.D., Ph.D., MBA

ni!. o" tah #choo$ o" Medicine % &A Medica$ Center ni!. o" tah #choo$ o" Medicine % &A Medica$ Center



Functions o" the Kidney

' ()cretion()cretion o" *aste products o" meta+o$ism and druso" *aste products o" meta+o$ism and drus

' -eu$ation-eu$ation o" homeostasis o" +ody *ater o" homeostasis o" +ody *ater

homeostasis o" ions in the +ody homeostasis o" ions in the +ody

+$ood !o$ume and pressure +$ood !o$ume and pressure

' (ndocrine(ndocrine /0ormona$1 Functions/0ormona$1 Functions

' (rythropoietin 2 stimu$ated red +$ood ce$$ "ormation(rythropoietin 2 stimu$ated red +$ood ce$$ "ormation

' -enin 2 contro$s +$ood pressure-enin 2 contro$s +$ood pressure

' Ca$citrio$ /acti!e "orm o" !itamin D1 2 +one "ormationCa$citrio$ /acti!e "orm o" !itamin D1 2 +one "ormation



3(P0-O3 2 the Basic Functiona$ nit o" the Kidney3(P0-O3 2 the Basic Functiona$ nit o" the Kidney

One mi$$ion nephronsOne mi$$ion nephronsper 4idney in humansper 4idney in humans



Orani5ation o" 3ephrons and B$ood &esse$s

Source: Vander’s Human Physiology. MCGraw-Hill Higher Education

C or t ex

M

e d ul l a

6nside a Microchip6nside a Microchip



3ephron3ephron is a 0ih (""iciency Processin nitis a 0ih (""iciency Processin nit

http://www.youtube.com/watch?v=glu0dzK4dbU








Kidney is a 0ih (""iciency P$antKidney is a 0ih (""iciency P$ant

' 6n humans +oth 4idneys account "or 7.89 o" +ody *eiht6n humans +oth 4idneys account "or 7.89 o" +ody *eiht

' But they recei!e 89 o" cardiac outputBut they recei!e 89 o" cardiac output

' Cardiac output in a hea$thy adu$t is ;.< $iters=minCardiac output in a hea$thy adu$t is ;.< $iters=min

' #o, >. $iters o" +$ood passes throuh 4idneys e!ery minute#o, >. $iters o" +$ood passes throuh 4idneys e!ery minute /;.< @ 7.8 >.1 /;.< @ 7.8 >.1

' ota$ !o$ume o" +$ood in a hea$thy adu$t is . $itersota$ !o$ume o" +$ood in a hea$thy adu$t is . $iters

' 6t ta4es on$y 8 min "or the *ho$e +$ood in the +ody to pass6t ta4es on$y 8 min "or the *ho$e +$ood in the +ody to passthrouh the 4idneys /. $iters >. $iters=min 8 min1throuh the 4idneys /. $iters >. $iters=min 8 min1

' 3o manmade machine or "i$ter can reach such e""iciency *ith3o manmade machine or "i$ter can reach such e""iciency *ith thethe

i!en si5e o" the "i$terin unit 2 the 4idneyi!en si5e o" the "i$terin unit 2 the 4idney



-ena$ 0and$in o" Water, ($ectro$ytes and #o$utes-ena$ 0and$in o" Water, ($ectro$ytes and #o$utes

#u+stance#u+stance Fi$teredFi$tered ()creted()creted -ea+sor+ed-ea+sor+ed 9 Fi$tered9 Fi$tered$oad rea+s.$oad rea+s.

Water Water

aa

>E7>E7 >.8>.8 >E.8>E.8 <<.<<.

3a3aGG

++

8,778,77 >87>87 8,7878,787 <<.;<<.;

KKGG

++

77 >77>77 77 E.>E.>

CaCaGG

++

8;78;7 >7>7 8787 <E.<E.

++

aa

L=dayIL=dayI

++

m(J=dayIm(J=dayI

cc

mmo$=dayImmo$=dayI

dd

=day=day



Water 0and$in +y the 0uman Kidney

Fi$tered Water>E7 L=dayFi$tered Water>E7 L=day

-ea+sor+ed Water>E.8 L=day-ea+sor+ed Water>E.8 L=day

()creted Water..>.8 L=day()creted Water..>.8 L=day

Fractiona$ -ea+sorption.....<<.9Fractiona$ -ea+sorption.....<<.9



Fractiona$ -ea+sorption o" Water !s. Dai$y rine OutputFractiona$ -ea+sorption o" Water !s. Dai$y rine Output

9979899100

0

1

2

3

4

5

6

99.2% 98.6%

0.6%

ractional !ea"sor#tion $%&

' a i l y ( r i n e

) u t # u t

$ * i t e r

s &



#tar$in Forces and H$omeru$ar Fi$tration -ate /HF-1#tar$in Forces and H$omeru$ar Fi$tration -ate /HF-1

KK" " Fi$tration Coe""icient o" Fi$tration Coe""icient o"

$omeru$ar +ed$omeru$ar +ed

> sJ meter



Water A+sorption A$on the 3ephronWater A+sorption A$on the 3ephron

AJuaporin> AJuaporin>

AJuaporins, % ; AJuaporins, % ;



#tations 6n!o$!ed in Water Processin +y 3ephron#tations 6n!o$!ed in Water Processin +y 3ephron



6nteration o" Processin +y 3ephrons and B$ood &esse$s6nteration o" Processin +y 3ephrons and B$ood &esse$s



Desin o" the Kidney as 0ih (""iciency P$ant

' niJue architectureniJue architecture and arranement o" nephrons and +$oodand arranement o" nephrons and +$ood!esse$s 2 compara+$e to the desin o" a physica$ p$ant!esse$s 2 compara+$e to the desin o" a physica$ p$ant

' O!era$$ "unctionO!era$$ "unction o" the 4idney is the sum o" the "unctiona$o" the 4idney is the sum o" the "unctiona$capacity o" each nephroncapacity o" each nephron

' 0ih input0ih input o" ra* materia$s and hih processin capacityo" ra* materia$s and hih processin capacity

' #tations:#tations: Di""erent sements o" nephronDi""erent sements o" nephron

' Machines:Machines: Di""eent aJuaporins and ion transportersDi""eent aJuaporins and ion transporters

' #upp$y Chains#upp$y Chains "or ra* materia$s: B$ood !esse$s arteries"or ra* materia$s: B$ood !esse$s arteries

' De$i!ery $inesDe$i!er y $ines "or the "inished product co$$ectin ducts"or the "inished product co$$ectin ducts

' -ecyc$in mechanisms:-ecyc$in mechanisms: rea+osorption throuh capi$$aries,rea+osorption throuh capi$$aries,

*hich drain into !eins*hich drain into !eins



Princip$es and Metrics o" Process Ana$ysisPrincip$es and Metrics o" Process Ana$ysis />=1/>=1

' Process Boundaries:Process Boundaries: H$omeru$us /entry point1 to the end o" theH$omeru$us /entry point1 to the end o" the

co$$ectin duct /e)it point1co$$ectin duct /e)it point1

' Process F$o* Diaram:Process F$o* Diaram: A$ready sho*n A$ready sho*n

' Capacity o" (ach #tation in the Process:Capacity o" (ach #tation in the Process: A$ready discussed A$ready discussed

' Process Capacity:Process Capacity: #ummation o" the capacities o" indi!idua$#ummation o" the capacities o" indi!idua$nephrons /> mi$$ion in each 4idney1 2 much hiher than *hatnephrons /> mi$$ion in each 4idney1 2 much hiher than *hat isis

needed to hand$e *ater e!en at times o" increased demand.needed to hand$e *ater e!en at times o" increased demand.' Capacity ti$i5ation:Capacity ti$i5ation: O!era$$ capacity uti$i5ation under norma$O!era$$ capacity uti$i5ation under norma$conditions is a+out 7.conditions is a+out 7.



Princip$es and Metrics o" Process Ana$ysisPrincip$es and Metrics o" Process Ana$ysis /=1/=1

' hrouhout -ate /F$o* -ate1:hrouhout -ate /F$o* -ate1: At $omeru$us >8 m$=min />E7 $iters "i$trate per day1 At $omeru$us >8 m$=min />E7 $iters "i$trate per day1

F$o* rate decreases dramatica$$y to*ards the end to a+out >F$o* rate decreases dramatica$$y to*ards the end to a+out >m$=min />.8 m$ urine = ; hours1m$=min />.8 m$ urine = ; hours1

' F$o* ime:F$o* ime: #ome *hat di""icu$t to determine#ome *hat di""icu$t to determine

' Cyc$e ime:Cyc$e ime: For *ho$e +$ood in the +ody /. $iters1 it is a+out 8 minFor *ho$e +$ood in the +ody /. $iters1 it is a+out 8 min

' Process ime:Process ime: For > $iter o" +$ood is 7.E min /8 . 7.E1For > $iter o" +$ood is 7.E min /8 . 7.E1

' 6d$e ime6d$e ime: For acti!e$y processin nephrons there is no id$e time.: For acti!e$y processin nephrons there is no id$e time. For the nephrons at rest /79 under norma$ conditions1 For the nephrons at rest /79 under norma$ conditions1

there is id$e timethere is id$e time



u+u$o$omeru$ar Feed+ac4 Mechanism /HF1u+u$o$omeru$ar Feed+ac4 Mechanism /HF1



6nsihts into Process F$o* "rom Hene Knoc4out Mice6nsihts into Process F$o* "rom Hene Knoc4out Mice

' Hene 4noc4out techno$oy pioneered +y Pro". Mario CapecchiHene 4noc4out techno$oy pioneered +y Pro". Mario Capecchi

' Pro!ides e)treme$y use"u$ too$s into +io$oica$ processes andPro!ides e)treme$y use"u$ too$s into +io$oica$ processes and ho*ho*they operate and ho* they can +e deranedthey operate and ho* they can +e deraned

' Hene codin "or a particu$ar protein is suppressed at ear$yHene codin "or a particu$ar protein is suppressed at ear$y

em+ryonic staeem+ryonic stae

' echno$oy has ad!anced to the e)tent that *e can 4noc4out theechno$oy has ad!anced to the e)tent that *e can 4noc4out thetaret ene "rom speci"ic ce$$s /or stations1 in the 4idneytaret ene "rom speci"ic ce$$s /or stations1 in the 4idney

' sin this techno$oy speci"ic aJuaporins ha!e +een 4noc4edsin this techno$oy speci"ic aJuaporins ha!e +een 4noc4ed out inout inthe 4idneys o" micethe 4idneys o" mice

' When speci"ic aJuaporins are de$eted, each de$etion producedWhen speci"ic aJuaporins are de$eted, each de$etion produceddi""erent types o" de"ects at the indi!idua$ stations, or atdi""erent types o" de"ects at the indi!idua$ stations, or at the *ho$ethe *ho$e

anima$ $e!e$.anima$ $e!e$.



Knoc4in o" AJuaporin>, the Machine at #tation >Knoc4in o" AJuaporin>, the Machine at #tation >

Knoc4in out AJuaporin> had sini"icant e""ect +oth at station > and atKnoc4in out AJuaporin> had sini"icant e""ect +oth at station > and at

the *ho$e 4idney $e!e$.the *ho$e 4idney $e!e$.

At #tation > At #tation > At Who$e Kidney At Who$e Kidney



Knoc4in o" AJuaporin;, the Machine at #tation ;Knoc4in o" AJuaporin;, the Machine at #tation ;

Knoc4in out AJuaporin; had sini"icant at station ; on$y *ith modestKnoc4in out AJuaporin; had sini"icant at station ; on$y *ith modest

e""ect at the *ho$e 4idney $e!e$.e""ect at the *ho$e 4idney $e!e$.

At #tation ; At #tation ; At Who$e Kidney At Who$e Kidney



Future Perspecti!esFuture Perspecti!es

App$ication o" princip$es o" operation *i$$ pro!ide: App$ication o" princip$es o" operation *i$$ pro!ide:+ Better understandin o" norma$ 4idney "unctionBetter understandin o" norma$ 4idney "unction

+ 3e*er insihts into the disease processes3e*er insihts into the disease processes

+ -ationa$i5ation o" dru de!e$opment-ationa$i5ation o" dru de!e$opment

+ 0e$p identi"y e""ect o" dru interactions +ased on process "$o*0e$p identi"y e""ect o" dru interactions +ased on process "$o*

+ Open a ne* interdiscip$inary "ie$d to ad!ance 4no*$edeOpen a ne* interdiscip$inary "ie$d to ad!ance 4no*$ede



he (ndhe (nd



Manitude o" Kidney Diseases in the #A

' Chronic Kidney Disease /CKD1 2 mi$$ion = <7,777 die each year Chronic Kidney Disease /CKD1 2 mi$$ion = <7,777 die each year

' Leadin cause o" CKD 2 dia+etes me$$itus and hypertensionLeadin cause o" CKD 2 dia+etes me$$itus and hypertension/account "or =rds o" a$$ CKD1/account "or =rds o" a$$ CKD1

' 3um+er o" (#-D /(nd#tae -ena$ Disease1 patients in the #A3um+er o" (#-D /(nd#tae -ena$ Disease1 patients in the #A

877,777 2 Medicare cost in 77 *as +i$$ion877,777 2 Medicare cost in 77 *as +i$$ionBy 77 (#-D patients >. m, Medicare cost 8. +i$$ionBy 77 (#-D patients >. m, Medicare cost 8. +i$$ion

' Acute Kidney Fai$ure 2 an 6C condition 2 a""ects 89 o" a$$ Acute Kidney Fai$ure 2 an 6C condition 2 a""ects 89 o" a$$hospita$i5ed patients *ith a morta$ity rate o" N 879hospita$i5ed patients *ith a morta$ity rate o" N 879

' One mi$$ion Americans su""er "rom 4idney stones. Most o" themOne mi$$ion Americans su""er "rom 4idney stones. Most o" them areare

aed +et*een 7 to ;7 yearsaed +et*een 7 to ;7 years

' Anemia associated *ith 4idney "ai$ure > +i$$ion annua$ mar4et 2 Anemia associated *ith 4idney "ai$ure > +i$$ion annua$ mar4et 2

pharma iants "ihtin nec4 to nec4, o"ten in the courtspharma iants "ihtin nec4 to nec4, o"ten in the courts



Centra$ Contro$ o" Water Processin +y the KidneyCentra$ Contro$ o" Water Processin +y the Kidney



#ensors 6n!o$!ed in Centra$ Contro$ Mechanisms#ensors 6n!o$!ed in Centra$ Contro$ Mechanisms



C$inica$ App$ications o" Process F$o* in 3ephronC$inica$ App$ications o" Process F$o* in 3ephron

Deranement o" process "$o* in a num+er o" c$inica$ conditionsDeranement o" process "$o* in a num+er o" c$inica$ conditions

Dia+etes 6nsipidus:Dia+etes 6nsipidus: /Water Dia+etes1/Water Dia+etes1

An um+re$$a roup o" disorders 2 e)cess *ater $oss An um+re$$a roup o" disorders 2 e)cess *ater $oss

6nherited /rare1 or acJuired /common1 "orms6nherited /rare1 or acJuired /common1 "orms AcJuired D6 is o"ten due to de"ecti!e "unctions o" one or AcJuired D6 is o"ten due to de"ecti!e "unctions o" one ormore stations a$on the nephron /o"ten station ;1more stations a$on the nephron /o"ten station ;1

Loop Diuretics:Loop Diuretics: /e.., Furosemide o" Lasi)1/e.., Furosemide o" Lasi)1

6nhi+it the "unction station 86nhi+it the "unction station 8-esu$ts in reduced *ater a+sorption at station ;-esu$ts in reduced *ater a+sorption at station ;Loss o" *ater in the urineLoss o" *ater in the urine

kishore slides

Documents