00

0
BASICS OF BONE AND MINERAL
METABOLISM

'fypes of bones 00:01:25

• eorHc.oJ bone/ eompo..ct bone -+ sha.~ ~ lon.9 bones.

• n-o.beculo..r / eo.ncenous bone -+ ends o\l long bones1
vertebr~

c.omcru bone vs n-o.beculo.r bone :

--
Po..ro..meters cortic.oJ Tro..becu.lo..r

~~s Compo.cl bone Co.ncel\ous, spo~

Contribu..too to toto.l 80'h aO'h
bone ~
I
Predommnt sites Sha.~~ lof'9 end ~ lon_g bones,
bones vertebra.

Por-os~ 5-IS'h 30-90'h

~w-is.~wn Present Absent

meto.bolic Clciiv~ LOW Hi9h

2emod.eli~ relte LOW Hi9h

Predominc1nt PTH, th~:fO)(ine ~ono..do.l steroids,

honnonoJ control 5ca8 . ~ 768
- - ~--- - -- -

T score t o T E?,$ :
&mo CfJone mos~ oens~ / T 5c.ore) WP-S previrusl~ used to
di0-3nose osteoporos,s.
Tf?JS (Tro.beculo.r eone score); t-Jewer concept which looKs
into the tro.beculo.r bone strv.ctu.re.
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S-lr uclure COJl(l<!l\ous bone

• .::iii
Bone and mineral metabolism 00:06:42

SKeleton is hi_9hl~ "o.sculM, IO'h o~ -the total co.rdiac ou.tpu.t iS

to -the bones.
FunclionoJ unit o~ o.. corhc.o.1/ compo.ct bone : OS.teon.
FunctionoJ unit o~ o.. c.o.ncel\ous/spo~ bone: Tro.beculo..
Tro.beculOJ" bone hos increased sur~ Meo.. t o bone ~
nmo o.nd hence responsible ~or 80~ ~ -the total bone
turnover.
Tro.beculM bone shows increased e,mo while being treo..ted.
~r osteoporosis.

Constituents ~ bone
~ne constituents

Cells (a1,4)
• ~ e s (gs'4)
• osteoblo.sts
• ost eocla.sts
• E?>ooe linin.9 cells

i 5calf3~bclof68 04 3c01168
f ----~
I 1nor.9o.n1c moir"IX
(<oo-10'.\)
0r.9o.nic ma.tri>< (30-40'4)
• T~pe I coll~en (go'4)
• Calcium • tJon col\~ en proteins (541)
~
u • Phosphorus osteopontln
C'O • ~ neslum OSteoCAlcln
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Q NNt SS Medicine• v5.0 • Marrow 5.0 • 202 1

Page 2{7
 O\her non col\aeen prot eins. :
Thrombo~ndin.
mo..-h"i>< ~ protein.
Flbronect in.

Cartilage types and distribution 00:11 :36

- ~ ~pe l Oistribu.tion

\ tJoncc..rtilo...9inous connective t iS&u.es, inclu.dins

bone, tendon, skin
-
"\\I iI ~eosible
Co.rtilaee, Vl~ OUS humor kevlnjoymandhra@gmail.com

connective tiS&u.es, inclu.dins Skin, \un,9,

vosculo.r s~stem
I
lV €>nsernent membrones

V minor component in ti~ues conto..inin.9 col\aeen I

V1 muscle o.nd most connecfo/e tis~u.es

vn oermoJ : epider~ junction

V\\I endothelium o.nd other ti~ues

lX T~u.es conto..inin.9 col\aeen \I

X ~pertrnphic co.rt,io.se

qenetlc o.s&ocio..tions o~ bone meto..bolism disorders :

6'ene or enz~me Oiseo..se

A~-\ected

COL..,IAI. COLIAa Osteo.9enesis irnper~cto.. ~pe lb

Osteop<>rosis
fhlers- Do.nlos s~ndrome, Sub~pe
Q!"throchoJosio..

COLaAI Severe chondrod~fplos,o..

osteoo.rfurit is

ehlers oanlos s~ndrome, suh~pe

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(.) vo.sculo.r
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Q Neet 55 Medicine • v5.0 • Marrow 5.0 •

 qene or enz~me Oise o.se
A~~ec-ted
COL4A3-COL41¼> Alport s~ndrome Ca.u.tosomoJ and
x-linked)

COL1AI epidermol~ sis bul\osa. (~strophic)

COLIOAI Schmid metaph~seoJ
Chond.r od~jSplo.sio..
,__

COLSAt, COLSAa, e.hlers-oonlo s s~ndrome, su.bt~pe

COUAt cl~ icoJ

COL3At. teno.scin x e, e.hlers Danlos s~ndrome, ~ p e

(Th.lxe,) h~permobil ~

~ s~I ~drox~lo.se e.hlerS-DoJ)\OS S~ndrome. s~pe

k~phoscoliosis

ADAm e.hlers-DoJ)los S~ndrome, ~pe

metoJopeptido.se dermo..tosposax:is
with thrombos-
pond.in ~pe I mofi~
CADAmTsa) (also
coJ\ed procol\~en
tJ-proteino.s e)

~s~I oxido..se menkes diseo.se

Bone mineralisation 00:1 6:36

CoJciwn H~drox~OfD._ti-te iS ~ r med ~ om runorphous coJcium

(UJhich 9ets ~rst converted t o coJcium phospho..t e).
rno..tri)( hos to be mineralised wifu inor9anic mineroJs.
minero.lisation o~ the ma.½ri)( occurs o..t -the
rnetaf)h~seo.l ends, with the help ~ t he mo..trix: vesicles
pre$ent o..t -the meto..ph~seo.l ends ~ the bone.
e.n~~~ ~~dy{~ vesicles :
• AIKoJine phosphoJo.se CALP).
f • s) tJu.cieotid.a.se.
I • Ame)(inS.
ALP o.nd s) nuclet\do.se o.re increo.sed in cholesto..tic liver
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diseo.ses o.lso, €:\Eff enz~me is spec.l\\c to the liver.
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Q Neet SS Medicine • v5.0 • Marrow 5.0 • 2021

 00 Basics of bone
and mineral
metaboflsm
T~pes ~ bone ~rmo..tion :
• enchondroJ bone ~rrnoJion.
G
• \n-tro.membrMOus bone -9ormo..-tion : Cla.vici e, sKuJ\ bones.
OSteoblo.st ~ t ion ~rom -the mesench~moJ cel\s requ.ire
run Xa o.s o.. transcription ~ ctor.
So, run xa tro.nscription ~ tor mu.to.Hon co.uses cleidocro.nioJ
~splo.sio..

~ cnd.ochondro.l
bone -Vorr'f')Qfoo

Chondro blosts

~ lntrame mbro.nous
bone~n
osteobla.sts

Osteo blasts and osteo cytes 00:21 :30

osteoblosts ori.9ino±e .\1'om the mesen c~moJ stem cells

Cmsc), transcription ~o.clor is requir ed is runxa..
osteoblosts secret es -the or.9o.nic mo..-tr-ix which is ~urthe r
mneroJiSed. o.nd -then eel\ becomes o.n osteoc ~e.
Function ~ the osteocute : mecho .noreceotor ~ctio n t o
J kevinjoymandhra@gmail.com
sense the d~ree ~ loo..di"'3 o.nd unloo.din.9 ~ the joint .
ost~ tes ore the maste r re.9uJo.tors ~ bone ~ rmo..tion
o.nd. resorpnon.
ALP h~drol~ses the inhibit ors o~ mineranso.tion o.nd thus
promo te bone minero.Jistion.
ALP is the moJ"Ker ~ bone minero.Jiso.tion.
mecho.nism o~ bone ~onna±ion :
Old ~ pothesis : oone is mlnero.Jlsed. ~om ou.-tside to inside
b~ osteoblCl.Sts. I
tJew h~e sis: e,one is mlneroJlsed ~om Inside to ov..-tside j
b_i:, the osteoc ~es.

.:¥:.
ost~ tes secret e the ~ l\owin.9:
0
C'O • FqF-a.a : It inhibits the ~ l\owin,g enz._i:,mes :
..a
""O 1. Sodium-phosphorous co -tr-o.nsp 0rter in the PCT o-9 the
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n Neel SS Medicine • v5.0 • Marrow 5.0 • 202 1 ,..,, ___ C.17

 6 Sub Topic Name 00

Kidne~s, COJ.A.Sri.9 increo.sec:l excretion~ -the

phosphorous (it iS the most potent phospho..-turic
substance in -the bo~ .
a. a - h~drox'11ose o.nd. inhibit -the -9.ormo.iion ~ o..clive
v.to.min o.
• Sc.lerostin.
\+ inhihlts the osteob\o..sts 0-nd -thus inhibrnn.9 bone
~rmoJion b~ inh1b1-t1n9 the W~T po..~
\t o..c-\i"o..tes osteoclo.s-\s o.nd bone resorption.

rr«l"orc4I
- ~<ltllc...,.._, ~
t

"""""'llil~.....- -.....__.....__..._. :::;,.,-

~-.,. -~~

Osteoclasts 00:29:22

1t is o.. mJJtinu.cleo±ed eel\ which ori9 ina.tes ~om the

mo..cr~es.
~ l'5o.nd is produced b:j -the osteoblosts o.nd binds to -the
~ receptor on the sur~ClC-e o~ -the osteoc.\Mt pr~nitors
and o.cbvaie osteoclo.st.
PTH and v1t 0Jnin D inc.reo..ses -the produ.c·hon ~ ~t'\ liSc.md
~om the os¼eoblo.sts and -thus increa.ses bone resorption.
Co.lci-tonin btnds to receptor on bo..stAI SAAr~ce ~ osteoclo.sts
o.nd thlAS \nhtb itirs it s a.ction.
Co.lcitonW1 c.o..uses ~PocaJcem,a. b~ stimulo..tiOn ~ the r eno.l
eo..a• cleo.rance.
I es~a.d\01 decrea.ses the osteoc.la.s-t: number, inhibiti"9 the

I bone resorption.
~ Cos-teopronto~rin) mib~s 2.At-JK L o.nd 2.PIJK receptor
~
0 5~~M~o~ ~ siok>9\caJ conditions.
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Q Neel SS Medicine• v5 0 • Marro
 00 Bulca o1 bone
and mineral
metabollsm
Mechanism of action of PTH 00:30:31

Pni, Vito.min D.
i+
osteoblo.sts.
!
12.~l~o.nd.
i (inhibiW f - - 0 ~ (~eopronto3erirv.
12.~ L receptor.

i
o s ~ (1nh\bi~ f-- es-tro9en, coJcrtonin.
i
ex>ne resorption.

1rr~ulo.r co..v ~ ~med. b~ -the osteoclost resorpnon a.re

co.1\ed HOWShips lo..cuno..e.
Co-rbonic ~ cl.rose ~pe a enz.~me within the osteoclos-ts
.9enerates enoush protons ~ bone resorption.

Steps of bone cycle 00:36:1 3

1.Ac+iva.ton ~ osteoclosts.
a. 2esorption.
These a steps to.xe o.round 3 weeKs duro..tion.
3. 2eversa.l (c~ e ~om osteoclost precursor -to
O$teoblost precursors).
2e3uJo.ied b~ osteo~tes.
4. ex>ne ~rmo..tion (h~ osteoc~te).
s. mineroJisanon.
The$e 3 steps reqwre 3 monfus duro..tiOn.
oone remodel~ - s.chemc.die. rep-esenta½ion

06teoclo.st
&one
rernodeh"9 unit

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 CALCIUM METABOLISM : PART 1

CoJcum reo.bsorpt,on occurs \n Kidne~.

Toto.l bod~ stores o~ coJc\um \s 1000-12>00 s, ~ which
gq,2, percento.se is in fue bone.
o.to percent~ e in so\4 t iS~ue.
0 .1 percent o.se in e.cF.
A\fero..3e coJcium into.Ke \s 1000 m9 per ~ -
rnAXifnum o.bso.--pt1on occurs \nj ~unum (upper srnoJ\
kevinjoymandhra@i•l''~ l e).

C4lcium reo..bsorphon in fue r-.~

~ DiStoJ corWOL&.ted iubule
s~- 10'.'
I

i
~ L!- --_J
ProximoJ

Thici', COIi e ~
PrOl(irnoJ [ o.scencf ~
~,~o. lrnb
(aO'l--aS~
11"9 <all

Henle's
loop

P e r ~ ~ coJcium o.bsorptton :
.l\lek co.lcium o.bsorphon is a.a% or aoo m3.
Ou.t ~ 1000 mg, on\~ 4-00 fn9 is o.bsorbed bu.-t aoo °"'9 iS \ost
o.s intes-t\noJ secrehons.

Urinary calcium excretion 00:03:13

tJor moJ : 4msfK9/per ~ -

>4 fn91K_9 in a4 hours urine , H~perc.alcu.rio.. !
3
<4 r'n9/K3 in a4 hours urine : H~coJcu rio..
~
u 1
(lJ Common rne-to..bolic o.bnormoJ~~ wifu s-tone ~rmers is
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 192 Endocrine
System
22
0
CoJcium homeosto.sls

!)lg\~ CAIClum
1000""'9
Ab50'bed

l Cdlclum
400 ""'9

e.ctv-o.cellular Quid

I TI 1
I000 ""9
secr.U833bd516807043 f7768
e~enous
~cal CGlclum'
'1Colco.lclum
150""'9
IS() ""9 ""~
F',ltered qoc,c, rrsf~
1!.eAbs«bed. S"1SO "'o/ ~

l
urine
a.so "'o/~

CoJcium homeosto.sis in normoJ rumo.ns shou.>inS the runounts ~

co.lcium o.bsorbed. in the intestine ru-.d reo.bsorbed. b~ the K ~

Three mosl- common meto.bolic o.bnormali~ in sl-one

~rmers:
H~percoJcu.rio.. (,4 r'n3/K_S in a4 hours urine).
H~peruricosurio.. (,1 m3"K9 in a4 hours u.rine).
H~pocitro..turio.. (< 11 m3"K.9 in a4 hours urine).

\n h~percoJcu.rio.. -. Locp diuretics (e,o..rH:er's s~ndrome).

\n h~pacoJcurio.. -. Thio.zides (€\rtelmo.n's s~ndrome).

Gastro intestinal regulation of calcium absorption 00:07:56

It involves :
I. Active -tro.nscel\ulo.r dbsorpfun :

gs 'A o~ coJcium dbsorbed.

control\ed b~ vito..min o.
a. ~ ive po.ro.cel\ulo.r a.bsorption:

s~ ~ coJcium o..bsorbed.
l\!ot contrnl\ed b~ Vit o..min D.

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 22 Calcium 193
Metabolism :
Part 1

____)
T r ~ l o J CAicium transport \n Stnllll intest ine

~ elood
Limefl

CAicium ~o..tes into the enteroc~te ch<mnels """'- o.. tro.nsient

receptor po+entiru co.lclum chru"lnel (TIZ.Pvlo) fur0U9h the brush
bon:ter membro.ne Qlo"e o.. ~o..voro.ble electrochemicAI 3rculient. under
~'°'°3ic conditions, the co..tlon is pumped ou.t ~ the cell o..t the
bo.so'°-tero.l side ~o..i~ o.. ste~ electrochemico.l 3rculient b~ the
o..denosine triphospno..te consumi"9 pump ea.a•-ATPQ.se. v.:A-1en fuere iS
o.. maj<>r elevo..t\on ~ intro..~ toplo.smic ea.a•, the ~ n leo..ves the cell
USir9 the tJo:-ci,._a• ex~er. Po.s&ive CA.a• i ~ as well as e«lux is
sensitive to co.lcitriol, whieh binds the \/ltQJrtin o receptof (vocz).

Active -u-o.nsce\\uh.r o.bsorption :

9S4 ~ CAicium o.bsorbed in srroJ\ intesttne o.cll'llel~ cal\ed as

o.cl:ive kro.nscel\uJo.r o.bsorpoon and it iS cornrol\ed b~ ~a.min D.
• On bo.solcl..tera.l membro.ne,

1,as dih~ox~ D2> enters furoU9h basoloJera.l side Clnd.

einds to its receptor in nucleus

l
'2.ele<1Ses calbindin

l
'2.esponsible ~ eo..a• comin.9 in
• In o.pical membrone, trn.nsport ~ e l is coJ\ec.~bds1sao1 043bbtnsa
T~V(o is present i
Co.l\ed o.s o.ctive o.s on bo.solo.teral membro.ne ~-·-ea·· j
excho.n,¥r o.nd eo..a•- ATPAo.se excho.n.9er responsible ~r
~
0 pu.shn9 eaa.• ou.t is o.c.tive.
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0 Neet SS Medicine • vl .0 • Marrow 6.0 • 2022

 System

~h ie po..ro.c.ellulo.r po.. th~ :

Ont~ so% is goes vio.. this po.. th~ bu.t become signi
~co.nt 0
when coJcium into.ke )4 9/~ .

CAicium into.ke is regulo..ted b~ coJcitriol up to 3 g/~

into.ke o.nd no h~percoJcemio.. ca.used
-.
When into.Ke )4 9/d ~ -. t.,eru;ls t o h~rc oJce mio. .
o.c.compo.nied b~ h~pe rcoJ curh COJJSin.9 stone ~orrna.tion,
~rm ing milK o.lko.li s~ndrome.
!\lot regulo..ted b~ vito.min D.

This po..t hw~ Is not o..ctlvo..ted but o..s ea.a• o.rno

unt

inc~ es, more ea.a+ goes vio.. po.ra.cellu.la.r ~

00:14:46
Total Adjusted calcium (TAC)
mirv.
Total Ac!justed Co.lciwn (TAC)= Co..a+ + 0.8 (4-s..oJbu
seru m co.lcium le¥eFi~ ~-~ to 10.3 rrsfdi.
H~perco.lcemio.. : >~10..ffn3/di.
TAC is clinicoJI~ Si_gni~co.nt.
• 48'% is in ~ee ~rm (ionizecO.
• sa ~ o..s plo..smo.. ea.a+ ~ which 40 per cen t~ iS bound
to o.lbumin o.nd 1a o% is to o.nionic protein.

eonversion :
o.as mmot/lm-e =o.s milli equ.ivoJent/litre =1 mg/di o~ ea.a•.
ea.a+ is meo.su.red b~ ion sensitive elec-h'odes cmd nonno.l
vo.lues 4.tos to s.a.8 m,s/dl.

00:20:24
Calcium Sens ing Receptors (CaSR)

CoSl2. in po.raiht..foid:
6~a833bd616°d07043b0f7768
IOniseo. calcium is the sens ing point fur C.OS2 .
nds.
In po.ro.ih~fo id comes to pl~ immedio..tel~ in seco
f Ine r~ in iorn2ed co.lclum co.uses inhibition ~
PTH o.nd
I decr ~e co.uses o..c.tivcrlion o~ PTH.
PTH r~ul crle s co.lcium In co..se ~ ioniz.ed c~ci um
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0 Neel SS Medicine • v1 .0 • Manow 6.0 • 2022
Page 4/9
 22 Calcium 195
Metabolism :
Part 1
C4S2 is seen o..t fue boso\o..teroJ membro.ne o~ thic.K oscend-
i~ loop ~ Henle.
0
\n h~perc.oJc.emi°'1 bo~ exc.retes ou.t CAa♦ through u.rine b~
inhibitin9 reo.bsorption ~ co.lcium.

CoJclum homeostasis

o~~ co.1c1um
IOOO~
Ab~becl

l coJcu.m
~00~

L? ~ co.lclum
,so ""9

urine
asorrsfc:1a_~

CAicium homeost-o.siS in normal humo.ns shooli"9 -the o.mounts ~

ca.lciwn o.bsofbed in ~ intestine Md reo.bSOl'bed. b~ -the Kidne~

Free c.oJcium :
measured ~ ion sensitive elec-lrndes.
Co.rdinoJ o..cllons :

sensed b~ Co.5'2..
'2.eqwred. ~ : Co.rdio.c. m~oc~e contro.clili~.
tJeuromusculo.r o.clivi~
e,one mineroJisa±ion.

'2elo..non belween coJciu.m Md o.c.idosis :

Acidosis, co.uses increo.se in ~ee coJciu.m (H~percoJcemia)
o.nd. oJKoJosis causes decreo.se in ~ee coJciu.m (H~pcc.oJce-
mio).

Co..lciu.m o.nd. H♦ both co~tes t o bind to Cllbumin cmd when

pH ~ \s increase in 1-f" ---+ H. will bind t o oJbu.min bl.lt eaa•
COJV)()t bind, so ~ee eo..a• increoses.
i
Renal handl"!L 00:26:14
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0 IDS'k o~ c.aJciu.m reo.bsorption occurs a.½ PCT.
ro
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0 Neet SS Med1c1ne • vl .0 • Marrow 6.0 • 2022

 "196 t noocnne LL
System

-these ore mostl~ reo.bsorbed oJ PCT except ~r ~nesium.

ao to as ,,; CAicium reabsorbed o..t TALH. 0
S to 10'.4 o..t DCT.
CoJciu.m lost in urine 1 4 1n9/K.9 in a4 hours.
Oceurs o..t 3 levels ,
PCT.
Thiel-\ o.scend.1n9 loop ~ Henle.
OCT.

Bone modeling 00:27:40

Colcium reo.bsorptlon o..t PCT 1

80'A o~ CAicium o.bsorbed o..t level ~ PCT is p~ive

pa..ro..cel\uJOJ" tro.nsport medlo..ted b~ CLAUDl~a o.nd. iS PTH
kevinjoyma~~~~~~f.

12.est aoo is b~ a.clive tro.nscel\uJor transport medio±ed ~

TI2.PV5 o.nd TI2.PV<o o.nd is PTI1 dependent.

mecho.niSm and re9uJo..tion o~ co.lcium tro.ns.port o..,t ThicK As-

cendiri.s Locp o~ Henle (TALH):
\t iS po.ro..cel\uJM tro.nsport.
ThrOIJ.9h this po..thwo_:, CAicium ,rno.snes.ium 9oes in and
medio..ted b~ Cfo•.udin 1<o/1g or po.ro..cellilin tho..t increo..ses.
c.oJcwn reo.bsorption o..t TALH.

Bone remodeling - Schematic representation

ll'IIMCellular

Ctil· · .. •· ... ► c~· ........ •► Ca2••••• • • .. :::::·:•• •

Na' • ··

I
1 t l'IIQCelluflll - c.2•
2
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D Neel SS Medicine • v 1 0 • Marrow 6.0 • 2022

 22 Calcium 197
Metabolism :

At level o~ TALH a receptors present on bo.solo±ero.l

Part 1
0
membro.ne:
1.For PTI1 1
When Pn-4 binds to receptor -4 tnhlbl~ clru1.dJn 14 (which is
o.n inhibitor o~ c.lo.wiln IW -4 There b~ 1nc.reos1r19 c.lo.udin Ito
-4 c.o.lcum .9oes inside.

a. For CoSf2. : kevinjoymandhra@gmail .com

It ,s o..clive Md It's bindin.9 \S dependent on .\?fee calcium.

Whe"' coJcium inc.reo..ses inhibitS reo.bsorpbon Mid co.uses
excretion o~ CAicium.
PTI-\ increo..ses coJcium rea.bsorpnon
CoS(2. inhibitS coJcium rea.bsorption
Mech:inisms nnd regulation of calclum transport In
the thick ascending limb of Henle (TALH).

D
CUlN111'11

~
" ........,o
Claudln-14

In 1M TAI.Ji. calcium 11 ~ via parac.. ula, m«:haniam1 lhrcxq, a

poM ~ in pett by claudin-18 and claudn• 111. The actlvl1y ol lhe
IMl&' proletnS Is SUJlt)mllMd by daudln- 14, Whose ellp,esaion 19 conllOlled
by pa,afly,oid hormone (FTH) and Ca'·. PTH binds to ~• ,_plOf and
onhoblta 1he eap,euK>n ol deudln-14, wh..... extracellular NUld Ca'·
.,...,_ Ile calcium......ng NCeptOf (CaSR) and lncn1- clludln- 14
~ ,...,tt
- Tlw 1811bolorption ol Ca' In 11w TALI-l la 1h11 ol oppoelnu
. , . _ c,1 PTH and Ca'· llw'Ou~ their ~ O f l. Ct.ON 111/111, Claudln-16
and 18: PTH, pa,alhy,okl hotmone: PTH R, pnlhyrold l9CeplOr

AtOCT :
Acti\/e -tro.nsport occurs rned.ia.ted b~ PTH b~ T2PV5 o.nd
TI2.PV!o.
Co.lcium o..bsorphon is vita.min D dependent .
Order ~ mo.ximum PTH dependen~ : DCT ) TAL..H ) PCT.

PTH : I
Ver~ sensiti\/e t o smo.l\ dipS in ionised coJclum. i
Stimu.la..tor 0~ I o.lpho.. h~ox~lo.se .
..:::t:.
u PTH o.nd v1fo.min D t o.9ether increo.se ca.lc\um o..bsorptlon
co
..0
"'O OJ"td. Cl.ls.<> co.uses increo.sed reo.bsorption ~ co.lcium.
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 Pn-t in smoJ\ in-rermtttent doses c.o..uses bone ~mo..-tion bu.t
in con-tinuous stimu.loJion c.o..uses born resorption. 0
enhancers in-restinoJ llbsor ption b~ increo.sed co.Jcitriol.

Calcium transport in OCT

n-aneceflul• Cet· n-eneport

Bnofart•af
- - - -- - - -
· · ·►

· ··►

kevinjoymandhra@gmail.com

Summary 00:36:02

When decrease in pl!l.Sm(l co.lcium occurs ~ Increase in

Pn-t o.nd vice verso.. o.s re3u.lo..ted b~ CaS2.

Decrease in ionized
coJciurn

lno..ctlvo..t\on ~ C4512

lncreo.se in PTH

lno.ctivo..tion ~ Co.S.12

l,n S
cr
L:~~;:n_J
l increo.se in
L C4lcitf i01
lncreo.sed
reo.bsorpti<>n
f. _ j_
I locreo.se in o.bsorpt\o~

::,t.
u IJor'rnQJise C4leiurn levels
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□ Neel SS Medicine • v1.0 • Marrow 6.0 • 2022

Page 8/9
 Ho.W ,~ I
-
22 Calcium
Metabolism :
Part 1

PTH : a.- 4 minu.tes

CoJci-tt"io\ : to-8 hours
a.s(0\-0 02> : a- 2, wee.Ks

oe~nse °'90..lnst h~pocoJcemlo..

----- -
oecreosii
plo.smo.. Ca •

loo.cl\vo..tion o~ Co..a•
sensi"S receptor

t Po..ro..fu~roid
hormone releo.se

'v '/ ',,

! Frociiono.l renal t R.enoJ as-1drox~vito.min D3
ea...a• excretion \o.h~ rox~lo.se

,,
j CAa.. mobiliscilion ~om
t CoJcrh'iol s~nthesis
sKeleton o.nd ~ ti~ues

j CoJcmrio\ s~nfuesis

' I,

'--- t-Jormo.l serum CA' ' _ _t

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 CALCIUM METABOLISM: PART 2

Hypercalcemia 00:00:24

eose dis~lon 1

eose , : A too ~ear old ~male wi-th recurrent episodes

cevinjoymandhra@gmail .cotn
~ rn,\d un (2,-4 time~. tllrin_g one such episode, an us~
o.bd.ornen o.nd pelvis was done o.nd rt showed nepnrocrucinosiS
o.nd s~ne, o.nd s. CoJcium : II.Co ms/dL., PTH : 400 pg/mL
On~ in co.se 1, Pn-. , so r3/mL. SO probo.bl~ o.. CASe ~ p--~
~ o..fu~roidism.

eose a : A fc;O ~eo.r o\d mo.le, as~mptomo.±lc, with no

comorbiclmes, exper,encin:9 ~o.±t~ ~ -the post 3-4 rnomns,
o.nd. on evoJULilion s. CDJciu.m - 12,J rrsldL., Pn-. : ao f)9I'mL_j,,
s.co..t s.PJ, ➔ 12.uJe out moJ9noJ1~.

Cose 3 : An 18 ~eo.r old bo~ presented to fue ~ wtth

Cl.Cu.t e pa.in o.bd.ornen, no .9uo..rd,11_9 or r9icl~ present, on
evoJwmon s. coJciurn : 13.Co rrsldL., P™ : 15 ps/~, S.Pc : SJ
ms/ dL.t ➔ ChecK Vito.min D.

Cose 4 : A 45 ~eo..r old ~mo.le dio.anosed wi'th CA breo.st in

ao,a, w'\derwent treatment ~ -the same o.nd is. curr ent\~ in
rem~ion, and ho..s come bo.cK wtth severe bone, b<l.~ o.nd rib
po..in, on evo.luanon hers. CoJcum: 14.to msl dL..., PTI-1 : 15 P9/'mL
➔ '2u1e ou.t meta.sto.sis.

PTH de__pendent hypercalcemia 00:03:30

• most o~ the cases ~ h~rcalcemio.. o.re relo..ted _.

I Pa.ro.½honnone -+ Pn-1 dependent h~rcoJc.emio..
1 • c.o.lculote o.c!)usted total c4lcwn ~ albumin ~ 10.4 ""9f'ell.

.:::£.
• ChecK ~ Pn-1 levels in al\ h~percoJc.emio.. po..-tients.
u • tJonnoJ values o~ PT\-1 50-IOO P9/m.
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 23 Calcium
Metabolism:
201
Part 2
• Second 3ener0Jion mmmoro..diometric ~ ~/ sandwich
~ : meo.sures nto..ct PTI1 molecule (cold. chrun methocO.
0
~rM!cemlo..
I
.[ 1,
~~ ~ po.m.'"1~,rotd unrelo.½ed ~ po.rn½h~old
31o.nd .9to.nd
1
P™ MS \'O ro""8(lSe
1
P™ ho.s to 3et suppre~ b~
eru, be > so, 100, soo or e-...en Mlclum o.nd the vo.lues ho..ve
IOOO -to bet. so f'slml

~ : In 0-. p<ilient wifu h~perco.lcem~ even ~ s. PTH levels

Me beMeen SO-IOO r3/ rrt.., it implies 0-. po.ro..th~roid. ,910J'id
irn/Olveinent, os i~ it wos non po.ro..fu~roid. 3land rela.ted.,
Co.lcium lOOuki ho..ve ~ e d Pni, o.nd. Pni should ho..'lle
been ( so P.9'1mL
> SO P9'1dL -+ Presumed t o be -+ PTH exc.€S!).
Causes of hypercalcemia
Pwathy,oid Dependent Hypercak;emia
Prlmaty hyperparathyroidlsm
Tertiary hype!parathyroidism
Famiial hypocak:k.n:: hypercalcemia
Llthun-associated hypercalcemia
Antagonistic autoantlbodles to tne calcun-senslng recepeor
Pwathy,old-~1depeode11t Hypen:alcemle
Neoplasms
PTHrP dependent
Other humoral syndromes
Local Olleolytlc disease Oncludlng metastases)
PTHP.,__ t , o n ~ )
e - YlwTin D ection
lngNtior, of exceea vitamin D or vitamin D INllogues
Toplcel vtamln D INlogues
GrwlulomatouadilNM
Willilml 1yndrome
Thy,olDlcicol,II
Adllflelinlufflclency
kAJa,.,.,...
'-lllfaiue
0wonlc l1lf1ill flilu,1 with aplalllc bone diMMe
IIMloblaaion
0rU{j$
llllamln A inlOlclcallon
Mik-alkall syndrome
Thiault~
Thaooh~

PTHIP · Pa,111/lyrold re1a1eO pi'Oliln

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□ Neet SS Medicine • v1 .0 • Marrow 6.0 • 2022

 System

COm<nOn cause s fur PTHexce~ :

• Prirro.r~ h~perpo.roJh~roidism : m/c co.use ~ 0
h~percoJcemio..
,. Adenoma. 1 m.c.
a. H~perplo.slo.. CmerJ- 1, metJ ao). m.c ea.use iS
3. co.rcinomo.. (ve~ ro..re). PTH 1' PrlmM~

(me,QtJ/H~perpa.ro..th~roidism s.coJciuM 1' ~per

..J. s. phosphorus J,, po:ro.-
Jo.w -tumor s~nu.rome 1
Poro..~bromin gene/ CD 13). ~oidi sm

lm°'9in.9 ~ ~he po..ro..~roid gland : Tc.~ ses-w nibi scan.

P114 voJu.e usuoJI~ in -the rarse ~ S0-50 0 f>Sl'ml
tJormoJ s. phosphorus : a.s - 4.S mi
di.

• seco n~ ~perp o.ro.. ~roidiSm : occurs when s. coJcium is

scaa3 3bd~ ~ c relhia), o.nd is common\~ seen in O\D.

P114 1' Secon~

s. CoJc.iurr) -1r-- H~perpo.ra±h~roid.ism
s. Phosphorus t

• Terbo..r~ ~perpo.ro..th~foidism :
LOns sto.nding secondo.r~ ~perpo..ro..th~roidiSm -+
~perpla.stic gland o.denomo.. -+ PTH , 1000 pg/dL -+
Tertio.r~ h~perpo.ro..~ roidiSm.
USW>.11~ seen in Ions standing Ct'\D po..tients.

PTH t Terb~
S. Calcium 1' H~perpo.ro..th~roidism
s. Phosphorus 1'

• DrlJ.9 \J;duced h~perpo..ro.:th~roidiSm : Ltthiurn.

f C/F of_primary hyperparathyroidism 00:21 :47
I
Primo..r~ h~perpo.raih~roidism o..ccounts fur S0-80'A o~ o.l\
.:::.::.
0 coses.
cu
.D
"O Adenomo.. m.c Cast case~ , in~rior po..ro..th~roid mos~.
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D Neel SS Medicine • v1.0 • Marrow 6.0 • 2022

P..iue 3 9
 23 Calcium
Metabolism:
Part 2
Femrues me.
Ase 9roup : tao-80 ~ea.rs.
As~mptomo-.'tic.
Fo..ti9ue.
'2.ee.curent un o.nd stones (aoo).
< 40 'leo..rS -+ m~ S~ndrome -+ HtjperplO.Sio.. -.
~~me\r'iool ln\/Olvement ~ 4 3lcmds.
Pn4 i s. CAlciwn t -+ ~peroolciurio.. -+ stones -+
Obs-truclion, recurrent un.

eondmons. or.I~ seen in children (OJ.A.tosomoJ clomlno.nt-) :

Pn4 t s. CoJcium t Urine CoJcium J, -+ Calcium sensi09
receptor no\- ~tionirs-+ H~pooolc\urio..--+ FHI-\ CFo.milioJ
~ c ~ e m ia).
P~ ~ - - + €\0-.in ~ mu.tctlion--+ S. Co.lcium1' --+ Supre~
Pni --+ Pit-\J, --+ Jans.en meto.ph~seoJ chonclr~stroph~ --+
met~ ~splosio.. cmcl short sto..-lure.

DI~ between FFH ~81JM~W~07043b0f7768

FFH ~

Sever"~ mild $e'l/ere

P™ 1' J,
$. Calcium 1' 1'
u.rino.n-1 Calcium J, - -
Du.eke Co.lcium senslnS PTH receptor ,9C>.-in ~

~
receptor \os~ o~ ~ n IY'Uto..~n
m..d-o.non
--- -
mode o!/ irhe<it<lnce - Al.ltoSOlnell dominMt ~tosomo.l clomino.nt
-- -- -- ~

PTH < 50 _pj/dL 1cenario1 00:29:28

When PTH < 50 f>9l'm1 :

PTH- rp supres&es PTH.
l
PTH- rp <Po.ro..thormone pef>lide) -+ Po.ro.neoplashc peptide t
-+ os&>eio..ted with squ.osnous eel\ CA -+ Hence Pf.T scan
..::L
u rou.tinel~ clone -+ ,~ pTH <SO r9/ rrL ~ '2.ule Ol.lt moJi9no.nc~.
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 23
204 Endocrine
System 0
CD.Se a : s ~ eel\ c.o.rcinomo..

Presento..tion o~ po.nmeoplo..stic h~rcoJcemio.. :

I. Fo..ti9ue.
a. Acu..~ presento..tion I tJeurops~chio..½T"ic s~mptoms.
Acu.te abdomen.
Arrh~i os .

'll II

--- ~~:
Short QT Interval

11

QT \ntervoJ : t:ntire ventt"iculo.r o.c.tiv~ ---+ ~ining ~ Qr2S

Complex to end o~ T u.lo..ve ---+ io-1a smoJ\ boxes ---+ o.4-0.48
---+ normo.l QT \ntervoJ
~cem io.. : LOr-'9 QT \ntervoJ.

,f>T"M '- 50 p9"mL ---+ PeT $CM) tJormo.l -+ 2elcrllvel~ beH:eY-

pro9nosis ---+ ~ ~r Vito.min o ---+ as(OW03, 1,as(()-UaD2>
Levels.

as(oH)D2i-tJormru as(OI-Oo3 - ~
as(OWD2i t1'
1,as(ol-l)aoo t1' t,as(QWaD3 t1' 1,asCOI-Oaoo - tJormoJ
L _) ~ ........
. . ~ J y
·kevinJoyman hra@gi ail .com
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Vito.min D Twnor produc.i"3 miSc.co.uses
lntoxicc..hon 1a hy<l'o~lo.sej l
f. l Pheochr omoc~
Th~rotoxicOSIS
I ½1,nphorna.
So.rco\dos is
Add1SOn1s diseo.se
~~I
~ ~te CAlsoproduces
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 23 Calcium
Metabolism:
Part 2
Co.se 3 : SMcoidosis.
FlMl\~ ~ o.l\ <>\her co.uses ~ h~percoJcemio.. OJ"e ruled ou.t,
chec.K ~ metostosiS os~ol~tic h'jperca.lc.emio.. wi-th CA breo.st
(CASe 4-).

Diagnostic summary of hypercalcemia 00:42:34

t s. Cokum ~ H~perc.rucemlo..
Cheek ~-Or iPTH j l0russ ca.usins,
J J, -1
P™ '> saps/dl. Pru '- SOPWdl.. lhio.Zide
J, J, diute-tics
~id Cheek pr sphorus (co.use
co.use -l, h~ia.
J,
m.co.denomo... Pt o.lso)

J, I
'r~
~
Follow
i
2.ule out
Po.ro.neoplo.slic Vito.min D metostasiS
~o.ro.
co.use Flowe.ho.rt
, not
fu~fOiciism

Oth,er- CQUS,eS :
Squo.mous
cell
FHI-I
co.rcinomo..
Llmium
Tertio.r~
~po.r~oidism

s~~oms ~ h~perco.lcemio.. :
• ~ bones.
• ~ s-lones.
• Abdornino.l ?foo.ns.
• Ps~chotic moo..ns.
• Fo...ti9u.e overtones.

LoVibond. ~le
moJnto.ined.
~ itl.4dlnoJ ru'\d
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~ f\0.11 increased
-L
()
C'O H~perpo..ro..th~roid\sm + Aero.I osteol~s\s (terminoJ bone
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Q)
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 206 Endoer'n,e 23
System
Hyporcalccmla - Clinical Features

lmptfr9d ~ration . 1011 of memo,y, heedoen., drowliMN. leltwgy,

dl9olllntotton. confus,on, t.rttabfftty. depr~. paranoia, hal1uclnations,
ltlMla. apeect, m,fects v18Unl dislurbflnce,, dee~ (dUII lo cak:lllcatlon al
the Mrdrvm), prurit'-" ,,_tnl relnrd8tlon (lnfa~). stupo,, coma

Muscle - " " -· hypore!leMln or n'-'11 refleMe, , hypotonlttt, mytllgla,

arthratgln, bone pain , 1<>4n1effusion, chondroclllclno98, dwarfism pnfantt)

Clellrlllnteetlnll ~ OIAC2(2~

Loss cl appetite, dry mouth, thnt , polydlpale, neu-. vomttlng. constlpalon,

abdominal J)tlln, weight 1011, acute pencrealttl1 (celcifylngl, Plllllc ..-:.r, acute
gnstrlc dilation Reno!
Pol¥itl.~
Polyurln, noctun&, n@lll1roc,,lclno8ls, nephrollt~ls, lnle,stttlel nephltti9, ecute
and chronic renlll failure
imp«tArrt-
CD die , II CIller
Short QT~
Arrtiy1hmla, bradycardla, first-degree heart block, short ar lnlsval bundle
~tcmt
,........
brandl black, cardiac arrest (rare), hypertension, vatcul• calcrflcatlon

Calcification Band lceratopathy, r9d ay9 syndrome, conJunctlllal calcification.

Ml)IYocald noals. vaecui. calcMcatton. pn,ritus

Pseudoclubbin9: ~ e n in ~perpo.ro.ih~roidsm.

Investigations~in~Primary Hyperparathyroidism 00:52:34

Tc sestarnibi-+ o..vidl~ binds-+ mitochondrio..

Che~cells
f>o.ro.fu~:f Oid
~ {
Ox~ntic cells -+ pie~ ~ mrtochondrio.. -+ Tc
sesto.mibi.

Adenomo.s mo.in!~ comprise -+ o~nbc cel\s

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 23 Calcium
Metabolism:
Part2
x-~ ~ndin_9s in ~perpa-ro..fu~foidism:

O.~e bone resorplion (m.c).

~98M~O'Uf)penm~ r fuan bone -9orma.kion -+
ino..deq.AAte bone mlnero.Hso-.tion _. coJclum h~dr"o~e-trte -+
~o..ced b~ -+ Amorphous coJcwn phospno..te -+ Ver~ eo.sil~
res.or-pea ~ broKen d ~ -+ po..in, ~o..c.-\ures.
eone replo..ood. oJso ho..s ~brous tiS5ues -+ Osteitis ~brous
~ieo..

Subper'iosteoJ resorption on
the ro.dioJ side ~ ind.ex o.nd.
middle ~r19er ~ the proximo.l
o.nd middle phoJanx.

Aero.I
osteol~SiS

E,rown>s Twnor: mo..c.rnp~es, ~st

debris --+ Pseudo twnor

➔ x-r~ showir9 bone

resorption

I
i
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()
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' - - - ---+ x-r~ showi~
o.cro.l os-teol~iS

x-r~ SKul\ la:tero.l view

show~ endosteoJ resorptoo
wrfu reduced mineroJiU\hon
~ -the outer and inr'le\'" table
~ -the s><uJ\ : ~es·h.Je ~
srut and pepper Qf)peo.ro.nce
~ SY-ul\

---
lntra.corncoJ bone
resorption