M-K 03 Metabolisme Kalsium

7/25/2019 M-K 03 Metabolisme Kalsium

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Metabolisme Kalsium

Hafiz Suwoto


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Metabolisme Kalsium

Kalsium adalah mineral terbanyak ditemukandalam tubuh manusia.

Rata-rata seorang dewasa mengandung sekitar

1 kg, ! diantaranya terda"at "ada rangka. #airan ekstrasel $%#&' mengandung sekitar

((.) mmol, dimana sekitar mmol terda"atdalam serum.

*ebih kurang )++ mmol kalsium mengalami"ertukaran diantara tulang rangka dengan %#&selama waktu ( am. $Marshall, 1)'.
http://en.wikipedia.org/wiki/Blood_plasmahttp://en.wikipedia.org/wiki/Blood_plasma


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Nilai Normal : Serum Kalsium mem"unyai "engaturan yang

ketat dengan nilai normal total calcium (.(-(.

mmol/* $-1+.) mg/d*' dan normal ionizedcalcium 1.1-1. mmol/* $.)-). mg/d*'. Kadarkalsium darah ini diatur se0ara ketat terutamakadar ionized 0al0ium.

umlah kalsium total berbeda sesuai dengan

kadar albumin, suatu "rotein dimana kalsiumda"at terikat.

%fek biologis kalsium ditentukan oleh umlahionized calcium, dan bukan oleh kadar total

kalsium. 2onized0al0ium diketahui ternyata tidakberbeda dan "aralel dengan kadar albumin, halini berguna untuk "engukuran ion kalsium, bilakadar albumin tidak normal tentu ditemukankelainan metabolisme kalsium meski"un kadar

kalsium total di "lasma normal.
http://en.wikipedia.org/wiki/Albuminhttp://en.wikipedia.org/wiki/Ionizedhttp://en.wikipedia.org/wiki/Ionizedhttp://en.wikipedia.org/wiki/Albumin


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Kadar kalsium yang telah dikoreksi :

3ila ditemukan kelainan "ada kadar albumin, kadar kalsiumda"at ditentukan melalui suatu "roses koreksi.

Hal ini digunakan untuk menentukan kadar sebenarnya daritotal kalsium yang disebabkan oleh "erubahan "ada ikatankalsium-albumin. Hal ini memberikan "erkiraan bera"a

seharusnya kadar total kalsium bila kadar albumin beradadalam kisaran normal.

4 Kadar kalsium yang telah dikoreksi $mg/dl' 5 kadar total kalsium yangterukur $mg/dl' 6 +.7 $.+ 4 kadar serum albumin terukur $g/dl''

4 nilai .+ mem"resentasikan nilai rata albumin.

3ila terda"at hy"oalbuminemia $kadar albumin 8 normal'maka kadar kalsium yang telah dikoreksi akan lebih besardari "ada kadar total kalsium terukur akan teta"i kadarionized 0alsium akan lebih rendah.


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Sumber kalsium :

*ebih kurang () mmolkalsium dikonsumsi olehmanusia "ada diet yang normal.

3ila diet mem"unyai kadar susu yang rendahtermasuk bahan-bahan yang mengandung kalsiumtinggi maka asu"an dari diet akan rendah uga.

Sekitar +! $1+ mmol' diabsor"si di lambung dan )mmol akan keluar dari tubuh bersama fe0es.Sisanya akan diabsor"si di usus halus.

9itamin :meru"akan ko-faktor "enting "ada "roses

;intestinal absor"tionof 0al0ium


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Ekskresi :

=inalmemfiltrasi sekitar ()+ mmol "er haridan meresorb"si kembali sekitar () mmol,

sehingga kehilangan melalui urin hanya sekitar

) mmol/l.

=inal uga ber"eran mem"roses >itamin :menadi kalsitriol$1,()-bis?Hkolekalsiferol',

yang meru"akan bentuk aktif yang ber"eran

membantu absor"si di usus halus.

Kedua "roses diatas distimulasi oleh hormon

"arathyroid $@AH'.
http://en.wikipedia.org/wiki/Kidneyhttp://en.wikipedia.org/wiki/Calcitriolhttp://en.wikipedia.org/wiki/Calcitriolhttp://en.wikipedia.org/wiki/Calcitriolhttp://en.wikipedia.org/wiki/Parathyroid_hormonehttp://en.wikipedia.org/wiki/Parathyroid_hormonehttp://en.wikipedia.org/wiki/Parathyroid_hormonehttp://en.wikipedia.org/wiki/Parathyroid_hormonehttp://en.wikipedia.org/wiki/Calcitriolhttp://en.wikipedia.org/wiki/Calcitriolhttp://en.wikipedia.org/wiki/Calcitriolhttp://en.wikipedia.org/wiki/Calcitriolhttp://en.wikipedia.org/wiki/Kidney


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Peran tulang pada metabolisme kalsium :

Aulang ber"eran sebagai 0adangan "enyim"ankalsium terbesar karena ! total kalsium tubuhterda"at di tulang. :alam keadaan normal sekitar )mmol mengalami "ertukaran di tulang.

#al0ium da"at dibebaskan dari tulang oleh hormon"arathyroid.

#al0itonin ber"eran menstimulasi masuknyakalsium ke dalam tulang meski"un "rosesnyasendiri tidak di"engaruhi oleh 0al0itonin.

Rendahnya asu"an kalsium dalam diet da"atmenadi faktor risiko "ada "erkembanganosteo"orosis.

:engan mem"ertahankan keseimbangan kalsium

"roses osteo"orosis da"at di0egah.


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Organ-organ pengatur :

?rgan "engatur ter"enting adalah kelenar"arathyroid. Kelenar ini terda"at dibawahkelenar thyroid, dan menghasilkan hormon"arathyroid bila kadar kalsium darah

menurun. Sel-sel "arafolli0ular dari kelenar thyroidmenghasilkan 0al0itonin bila kadar kalsiumdarah meningkat.

Bkan teta"i dalam hal ini "eran @AH lebihmenentukan dalam "engaturan kadarkalsium darah.


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Kelainan yang ditemukan pada metabolisme

kalsium :

Hy"o0al0emia dan hy"er0al0emia meru"akan

kelainan yang sangat serius.

Renal osteodystro"hy da"at teradi sebagai

konsekwensi dari 0hroni0 renal failure yangberhubungan dengan metabolisme kalsium.

?steo"orosis dan osteomala0ia uga meru"akan

kelainan yang disebabkan oleh gangguan "ada

metabolisme kalsium.


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@eran Kalsium sebagai "engatur

kontraksi otot C

Dntuk teradinya kontraksi otot miosin harusberikatan dengan a0tin, akan teta"i tropomyosinyang terda"at dalam struktur filamen a0tin akanmemblok situs "engikatan "ada "rotein a0tin

sewaktu otot berada dalam keadaan relaksasi. 3ila kontraksi distimulasi oleh im"uls saraf maka

troponinyang terda"at dalam struktur filamena0tin akan menggeser tro"omiosin sehingga situs

"engikatan "ada a0tin terbuka dan da"at mengikatmiosin. @erubahan "ada struktur filamen a0tin akan

membentuk a0tomiosin dan kontraksi otot akanberlangsung. @roses "embukaan situs "engikatanini diregulasi oleh adanya ion #a66.


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Pengaturan oleh ion kalsium berlangsung sbb: 3ila saraf motorik memi0u timbulnya "otensial aksi "ada

sel otot akan dihasilkan suatu senyawa "en0etus beru"a

neurotransmiter. @erbedaan "otensial antara bagian luardan dalam akan mengalami "embalikan "olarisasi. Brus"olarisasi yang teradi dengan segera ditransmisikankeseluruh serat otot oleh A tubuli dan menembus sam"aike sar0omer. Setia" A tubulus berada "ada E line.

Sar0o"lasmi0 reti0ulum sangat sensitif terhada""erubahan "olarisasi itu. Selanutnya sisterna terminalismenadi "ermeabel terhada" ion #a66 dan akanmembebaskan ion tersebut ke sar0omer. #a66 ion akanmengikat tro"onin yang selanutnya mengikattro"omyosin dan membuka situs "engikatan "ada

"rotein a0tin, dan selanutnya akan mengikat miosin. 3egitu terikat "ada a0tin miosin akan meme0ah BA@

dan membebaskan energi yang di"erlukan untukmenarik filamen a0tin ke arah "usat sar0omer kontraksi otot teradi.


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Kontraksi otot ini akan terus berlanutselama masih terda"at ion #a66 bebas didalam sar0omer.

3ila stimulasi saraf berhenti makamembran dari sisterna terminalis dengan

0e"at akan memom"akan ion #a66 bebaskemabali ke sisterna. Menghilangnya ion#a66, tro"onin tidak da"at lagi mengikattro"omiosin, sehingga tro"omiosin akan

kembali memblokir situs "engikatanmiosin "ada "rotein a0tinkontraksi ototberhenti.


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Ryanodine Re0e"tor

Kanal "embebasan ion Ca++ pada membran

Retikulum sarkoplasmik sel otot$SR' disebut he

ryanodine receptor, karena rese"tor ini sangatsensitif terhada" alkaloid tumbuhan ryanodin.

Skeletal dan otot kardiak kontraksinya diaktifkan

bila ion #a66dibebaskan dari lumen SR ke sitosolmelalui ryanodin rese"tor.


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Activation of voltage-gated Ca++channels, by an action

potential in the T tubule, leads to opening of ryanodine-sensitive Ca++-release channels.

Ca++movesfrom the SR lumen to the cytosol, passing

through the transmembrane part of the ryanodine receptor,

& then through the receptors cytoplasmic assembly.

Ca++

cytosol

SR lumenryanodinereceptor

e!tracellular space

"T tubule lumen#voltage-gatedCa

++channel

T tubules$ invaginations of

muscle plasma membrane.

Voltage-gatedCa++channelsin the T tubulemembrane interact %ith

ryanodine receptorsin the

closely apposed SRmembrane.


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ultiple biological !unctions o! calcium #ell signalling

Feural transmission

Mus0le fun0tion

3lood 0oagulation

%nzymati0 0o-fa0tor

Membrane and 0ytoskeletal fun0tions

Se0retion 3iomineralization


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"istribution o! Calcium

Aotal body 0al0ium- 1kg4 ! in bone

4 1! in blood and body fluids 2ntra0ellular 0al0ium

4 #ytosol

4 Mito0hondria

4 ?ther mi0rosomes

4 Regulated by G"um"sG

3lood 0al0ium - 1+mgs $7.)-1+.)'/1++ mls4 Fon diffusible - .) mgs

4 :iffusible - .) mgs


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#one Structure $cellular and non-cellular%

2norgani0 $!'

4 HydroIya"atite - ! #a1+ $@?' $?H'(

?rgani0 $((!'4 #ollagen $+!'

4 Fon-0ollagen stru0tural "roteins "roteogly0ans

sialo"roteins

gla-0ontaining "roteins

4 J(HS-gly0o"rotein &un0tional 0om"onents

growth fa0tors

0ytokines


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#lood Calcium - &'mgs(&'' mls$)*+mmoles(,%

Fon diffusible - .) mgs4Blbumin bound - (.74 =lobulin bound - +.

:iffusible - .) mgs

4 2onized - ).4 #om"leIed - 1.( mgs

bi0arbonate - +. mgs 0itrate - +. mgs "hos"hate - +.( mgs

other4 #lose to saturation "oint

tissue 0al0ifi0ation kidney stones


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"iet :ietary 0al0ium

4 Milk and dairy "rodu0ts $1Lt 5 1gm' :ietary su""lements4 ?ther foods

?ther dietary fa0tors regulating 0al0ium absor"tion4 *a0tose4 @hos"horus

Calcium bsorption $'*.-&*+ g(d% @rimarily in duodenum

4 1)-(+! absor"tion

Bda"tati>e 0hanges4 low dietary 0al0ium

4 growth $1)+ mg/d'4 "regnan0y $1++ mg/d'4 la0tation $++ mg/d'

&e0al eI0retion


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echanisms o! /0 Calcium bsorption

9itamin : de"endent

:uodenum eunum ileum

B0ti>e trans"ort a0ross 0ells

4 0al0ium binding "roteins $e.g., 0albindins'

4 0al0ium regulating membranomes

2on eI0hangers

@assi>e diffusion


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1rinary Calcium :aily filtered load

4 1+ gm $diffusible'4 ! reabsorbed

Awo general me0hanisms4 B0ti>e - trans0ellular4 @assi>e - "ara0ellular

@roIimal tubule and *oo" of Henle reabsor"tion4 Most of filtered load4 Mostly "assi>e4 2nhibited by furosemide

:istal tubule reabsor"tion4 1+! of filtered load4 Regulated $homeostati0'

stimulated by @AH inhibited by #A >itamin : has small stimulatory effe0t stimulated by thiazides

Drinary eI0retion4 )+ - ()+ mg/day4 +.) - 1! filtered load


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Regulation o! 1rinary Calcium Hormonal - tubular reabsor"tion

4 @AH - de0reases eI0retion $0learan0e'

4 #A - in0reases eI0retion $0al0iureti0'4 1,()$?H'(: - de0reases eI0retion

:iet4 *ittle effe0t4 *ogarithmi0

?ther fa0tors4 Sodium - in0reases eI0retion4 @hos"hate - de0reases eI0retion4 :iureti0s - thiazides >s loo"

thiazides - inhibit eI0retion

furosemide - stimulate eI0retionOther Routes o! E2cretion

@ers"iration *a0tation


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:isorders of #al0ium and

@hos"hate Metabolism


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?utline

1. Re>iew of 0al0ium and "hos"hate

metabolism

(. Bbnormalities of 0al0ium balan0e

. Bbnormalities of "hos"hate balan0e

. %Iam"le 0ases


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Maor Mediators of #al0ium and

@hos"hate 3alan0e

@arathyroid hormone $@AH'

#al0itriol $a0ti>e form of >itamin :H'


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Role of @AH

Stimulates renal reabsor"tion of 0al0ium

2nhibits renal reabsor"tion of "hos"hate

Stimulates bone resor"tion 2nhibits bone formation and mineralization

Stimulates synthesis of 0al0itriol

Fet effe0t of @AHFet effe0t of @AH NN serum 0al0iumserum 0al0ium

OO serum "hos"hateserum "hos"hate


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Regulation of @AH

*ow serum P#a6(Q2n0reased @AH se0retion

High serum P#a6(Q:e0reased @AH se0retion


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Role of #al0itriol

Stimulates =2 absor"tion of both 0al0ium

and "hos"hate

Stimulates renal reabsor"tion of both

0al0ium and "hos"hate

Stimulates bone resor"tion

Fet effe0t of 0al0itriolFet effe0t of 0al0itriol NN serum 0al0iumserum 0al0ium

NN serum "hos"hateserum "hos"hate


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Regulation of #al0itriol


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?>er>iew of #al0ium-@hos"hate Regulation


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:ifferent &orms of #al0ium

Bt any one time, most of the 0al0ium in the body eIists as themineral hydroIya"atite, #a1+$@?,'.$?H'(.

#al0ium in the "lasmaC

)! in ionized form $the "hysiologi0ally a0ti>e form')! bound to "roteins $"redominantly albumin'

1+! 0om"leIed with anions $0itrate, sulfate, "hos"hate'

Ao estimate the "hysiologi0 le>els of ionized 0al0ium in statesof hy"oalbuminemiaC

P#a6(Q#orre0ted5 P#a6(QMeasured 6 P +.7 $ 4 Blbumin' Q


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?>er>iew of 3io0hemi0al Homeostasis


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?>er>iew of #al0ium 3alan0e


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%tiologi Hy"er0al0emia

2n0reased =2 Bbsor"tion

Milk-alkali syndrome

%le>ated 0al0itriol

9itamin : eI0ess

%I0essi>e dietary intake

=ranuomatous diseases

%le>ated @AHHy"o"hos"hatemia

2n0reased *oss &rom 3one

2n0reased net bone resor"tion

%le>ated @AH

Hy"er"arathyroidism

Malignan0y

?steolyti0 metastases

@AHr@ se0reting tumor

2n0reased bone turno>er

@agets disease of bone

Hy"erthyroidism

:e0reased 3one Mineralization

%le>ated @AH

Bluminum toIi0ity

:e0reased Drinary %I0retion

Ahiazide diureti0s

%le>ated 0al0itriol

%le>ated @AH


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%tiologi Hy"o0al0emia

:e0reased =2 Bbsor"tion

@oor dietary intake of 0al0ium

2m"aired absor"tion of 0al0ium

9itamin : defi0ien0y

@oor dietary intake of >itamin :

Malabsor"tion syndromes

:e0reased 0on>ersion of >it. : to 0al0itriol

*i>er failure

Renal failure

*ow @AH

Hy"er"hos"hatemia

:e0reased 3one Resor"tion/2n0reased Mineralization*ow @AH $aka hy"o"arathyroidism'

@AH resistan0e $aka "seudohy"o"arathyroidism'

9itamin : defi0ien0y / low 0al0itriol

Hungry bones syndrome

?steoblasti0 metastases

2n0reased Drinary %I0retion

*ow @AH s/" thyroide0tomy

s/" 211treatment

Butoimmune hy"o"arathyroidism

@AH resistan0e



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?>er>iew of @hos"hate 3alan0e


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%tiologi Hy"er"hos"hatemia

2n0reased =2 2ntake

&leets @hos"ho-Soda

:e0reased Drinary %I0retion

Renal &ailure*ow @AH $hy"o"arathyroidism'

s/" thyroide0tomy

s/" 211treatment for =ra>es disease of thyroid 0an0er

Butoimmune hy"o"arathyroidism

#ell *ysis

Rhabdomyolysis

Aumor lysis syndrome


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%tiologi Hy"o"hos"hatemia:e0reased =2 Bbsor"tion

:e0reased dietary intake $rare in isolation':iarrhea / Malabsor"tion

@hos"hate binders $0al0ium a0etate, Bl Mg 0ontaining anta0ids'

:e0reased 3one Resor"tion / 2n0reased 3one Mineralization

9itamin : defi0ien0y / low 0al0itriolHungry bones syndrome

?steoblasti0 metastases

2n0reased Drinary %I0retion

%le>ated @AH $as in "rimary hy"er"arathyroidism'


&an0oni syndrome

2nternal Redistribution $due to a0ute stimulation of gly0olysis'

Refeeding syndrome $seen in star>ation, anoreIia, and al0holism'

:uring treatment for :KB


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#ase 1

Mrs. A is a ) year old woman with a "ast medi0al historysignifi0ant for hy"ertension who 0omes for a routine 0lini0 >isit.She initially states that she has no sym"tomati0 0om"laints, butlater in the inter>iew des0ribes 0hroni0 fatigue and a mildly

de"ressed mood. Her eIam is unremarkable. *abs are asfollowsC

#al0ium $total' 4 11. mg/d* $normal T 7.)-1+.( mg/d*'

@hos"hate 4 1.7 mg/d* $normal T (.+-. mg/d*'

Blbumin 4 .7 g/d* $normal T .)-).+ g/d*'

@AH 4 1( "g/m* $normal T 1+-+ "g/m*'

#reatinine 4 1.( mg/d*


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#ase (

Mr. = is a + year old man with a history of al0oholism. He had not seen ado0tor for 1) years before "oli0e brought him to the %R after finding him0onfused and dishe>eled behind a lo0al 0on>enien0e store. 2n the %R, hewas thought to be 0onfused sim"ly due to intoIi0ation, but was admitted formild al0oholi0 he"atitis and marked malnutrition. His mental status 0learedu" about 7 hours after admission. :uring morning rounds on hos"ital dayU(, he 0om"lained of feeling fatigued and weak. *ater that day, the nurses

find him seizing. Ahe seizures sto" with low dose 29 diaze"am. Stat labsare sentC

Sodium 4 1 meL/*

@otassium 4 .( meL/*

#al0ium $total' 4 .7 mg/d* $normal T 7.)-1+.( mg/d*'@hos"hate 4 +. mg/d* $normal T (.+-. mg/d*'

Blbumin 4 1.7 g/d* $normal T .)-).+ g/d*'

#reatinine 4 1. mg/d*

#K 4 )++ D/*


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#ase Mr. H is a year old man with a "ast history signifi0ant forhy"ertension and #?@: from smoking ( "a0ks "er day for thelast + years. He "resented to an urgent "ulmonary 0lini0a""ointment with ( months of in0reased 0ough and ) days of;mild< hemo"tysis. D"on further obtaining further history, here"orts feeling fatigued, nauseous, and 0hroni0ally thirsty for

se>eral weeks. His eIam is signifi0ant for bilateral rhon0hi $no0hange from baseline lung eIam' and absent refleIes. Statlabs are ordered from 0lini0C

Sodium 4 17 meL/* #3#, @A/@AA 4 VF*

@otassium 4 . meL/* @AH - @endingMagnesium 4 1.7 mg/d* Blbumin 4 (.( g/d*

#al0ium $total' 4 1.1 mg/d*

@hos"hate 4 1. mg/d*

#reatinine 4 (.7 mg/d* $baseline 0reatinine 5 1.1'


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#ase

Miss * is a 1 year old woman with no signifi0ant "ast medi0alhistory, who is brought to the %R by her mother after she notedher to be a0ting bizarrely for the "ast se>eral weeks. Ahoughtto be a0ti>ely "sy0hoti0, a "sy0hiatry 0onsult is asked to seethe "atient, who re0ommends 0he0king routine labsC

Sodium 4 1( meL/* Drine toI. s0reen 4 Fegati>e

@otassium 4 .1 meL/* Drine "regnan0y - Fegati>e

Magnesium 4 (. mg/d*

#al0ium $total' 4 . mg/d*@hos"hate 4 . mg/d*

Blbumin 4 .( g/d*

#reatinine 4 +.7 mg/d*


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M-K 03 Metabolisme Kalsium