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DISORDERS OF
CALCIUM HOMEOSTASISBY
UNIT III
PROFESSOR :Dr. K.B.R.SASTRYASST PROF :Dr. P. ANURADHA
Dr. SUNEEL KUMAR
PGs :Dr. MUJEEB AFZAL
Dr. P.PRIYADARSHINI
Dr. ABDUL SAMAD
Dr. SURESH
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Approx 1000 to 1200 g calciumpresent in adult
99.3 % in bone & teeth ashydroxyapatite crystals
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Corrected calcium
For eery 1!g"d# drop in serumalbumin belo$ g"d# measuredserum calcium decreases by 0.'
mg"d#.
Corrected calcium ( measured Ca)*0.'x+!measured albumin,- +Calcium
in mg"dl albumin in g"dl,
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FUNCTIONS
/one
Coagulation cascade
eurotransmitter release Contraction o cardiac seletal and
smooth muscle
ndocrine and exocrine secretions 4ntracellular signalling
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Why is the stringent
control of extracellularcalcium concentrationimportant ????
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PARATHYROID HORMONE
Pre pro PTH ( ! ""#
Pro PTH ( $% "" #
PTH ( &' "" #
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PARATHYROID HORMONE
ACTION ON BONE 5elease o interstitial calcium and phosphate
6timulates osteoblasts $hich releasecytoines lie 4#!7 $hich actiate osteoclasts
8steoclasts cause release o
hydroxyproline calcium phosphate
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ACTION ON KIDNEY Calcium and phosphate are reely ltered in
the glomeruli
:hosphate is absorbed rom :C; throughsodium!phosphate co!transporter
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CA#C4 ?0 % ! :C;
20 % ! ;hicascending limb o
loop o henle
@ > 10 % ! C; C;
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4;6;4A# BA#4 8F CA#C4 '0 % o ingested calcium isabsorbed
=ainly in duodenum & DeDunum.
Absorption is both passie and actie
:assie E paracellular route nonsaturable @ % ingested Ca absorbedby this route.
ActieE transcellularE receptormediated 2@% ingested Caabsorbed.
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ROLE OF ITAMIN D
. Promotes intestinal calcium
absorption
/ 1. Formation o calcium bindingprotein
+calbindin, 2. Formation o calcium stimulated
A;:ase
3. Formation o alaline phosphatase
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CA#C4;84
:roduced by the paraollicular cells " C cells othyroid gland.
5emnants o ultimobrachial body
6;4=
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HYPERCALCEMIA
6erum calcium I 10.@ mg"dl +I2.@ mmol"l,
4oniJed calcium I @.3 mg"dl +1.3 mmol"#,
=ild E;otal ca 10.@!11.9 mg"dl +2.@!3
mmol"l, +i @.7!' mg"dl 1.!2 mmol"l, =oderate E ;otal ca 12!13.9 mg"dl +3!
3.@mmol"l,
i ca '!10 mg"dl +2!2.@ mmol"l,
6eereE ;otal ca 1!17 mg"dl +3.@! mmol"l,
i ca 10!12 mg"dl +2.@!3 mmol"l,
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EPIDEMIOLOGY
4ncidence 1!2 case per 1000 adults.
Bigher incidence in 6outh Arica and6candinaia.
=ales I emalesE diKerencediminishes $ith increasing age.
Bypercalcemia rom all causeincrease $ith adancing age.
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)HEN TO SUSPECT
HYPERCALCEMIA***
=any are asymptomatic
;he mnemonic LstonesL LbonesMNthronesM Labdominal groansL andLpsychic oertonesL describes theconstellation o symptoms and signs
o hypercalcemia
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Bypercalcemia can result in atiguedepression mental conusionanorexia nausea omiting
constipation reersible renal tubulareKects increased urination short O;interal arrhythmias
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Phen calcium I13mg"dl >calcication inidneyssinesselslungsheartsto
mach and renal insuQciency
Phen calcium 1@!1'mg"dl > coma
and cardiac arrest can occur
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CAUSES OFHYPERCALCEMIA
:A5A;B584 > 5#A; :rimary hyperparathyroidism
#ithium therapy
Familial hypocalciuric hypercalcemia
6olid tumor $ith metastases
6olid tumor $ith humoral hypercalcemia
Bematological malignancies
=A#4AC ! 5#A;
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CAUSES OFHYPERCALCEMIA
R4;A=4 > 5#A; Ritamin intoxication
6arcoidosis
4diopathic hypercalcemia o inancy
A668C4A; P4;B B4B /8;
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CAUSES OFHYPERCALCEMIA
A668C4A; P4;B 5A# FA4# alali syndrome
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:roximal muscle $asting easyatiguibility atrophy o muscles
uodenal ulcer
:ancreatitis
Asymptomatic primaryhyperparathyroidism
Bypercalcemic parathyroid crisis
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LABORATORY TESTS Bypercalcemia
Bypophosphatemia
5aised :;B
5aised alaline phosphatase
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LITHIUM THERAPY
4t shits the :;B cure to right inresponse to calciumi.e. highercalcium leels are reSuired to lo$er
:;B secretions probably acting atthe calcium sensor
;here is complete reersal ohypercalcemia $hen lithium isstopped
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FAMILIAL HYPOCALCIURICHYPERCALCEMIA
Autosomal dominant trait
Caused by inactiating mutation in asingle allele o the calcium sensingreceptor
Abnormal sensing o the bloodcalcium by the parathyroid gland and
renal tubule causing inappropriatesecretion o :;B and excessie renalreabsorption o calcium
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JANSEN+S DISEASE
Autosomal dominant
Actiating mutation in the :;B":;Br:receptor
6hort limbed d$arsm
Bypercalcemia andhypophosphatemia $ithundetectable or lo$ :;B leels
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MALIGNANCY RELATED
HYPERCALCEMIA
Bistological character o tumor ismore important than extent ometastases
=CBA46=6 Bumoral hypercalcemia o malignancy
irect bone marro$ inasion 6eletal metastases
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ITAMIN D INTO,ICATION
Chronic ingestion o 0!100 times thenormal physiological reSuirement oitamin
Bypercalcemia is due to increasedactiity in the intestine and bone
4t is the conseSuence o increased
leels o 2@ +8B , iagnosis is by documenting
eleated leels o 2@+8B,
I100mg"ml
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Gr"-/o0"1os 23se"ses
4n granulomatous diseases liesarcoidosis tuberculosis and ungalinections excess 12@+8B, is
synthesiJed in macrophages andother cells
;here is a positie correlation
bet$een 2@+8B, and 12@+8B, :;B leels are lo$
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)ILLIAM+S SYNDROME
Autosomal dominant
CharacteriJed by supraalular aorticstenosis mental retardation elnacies
4t is due to abnormal sensitiity toitamin due to microdeletions at
the elastic locus and other genes onchromosome ?
#eels o 12@+8B, are eleated
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HYPERTHYROIDISM
About 20% o hyperthyroid patientshae high!normal or mildly eleatedserum calcium
4t is due to increased bone turnoer$ith bone resorption exceeding bone
ormation
;6B itsel has a bone protectie
eKect
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IMMOBILIZATION
4t is a rare cause o hypercalcemia inadults in the absence o anassociated diseasebut may cause
hypercalcemia in children andadolescents
Pith resumption o ambulation
hypercalcemia returns to normal ;here is a disproportion bet$een
bone ormation and bone resorption
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THIAZIDE DIURETICS
4ncrease calcium reabsorption.
=echanismE 2 hypothesis proposed.
First hypothesis E
6econd hypothesisE increased aCaexchanger in /# membrane o C;
CFdepletio
n
ecreased calciumltrate
4ncreased $ater & a absortion in:C; driing increased Ca absorption
in :C;
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ITAMIN A INTO,ICATION
Calcium leels may be eleated aterthe ingestion o @0000 to 100000units o itamin A daily
4t is presumed to increase boneresorption
Pithdra$al o the itamin is usually
associated $ith promptdisappearance o hypercalcemia
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SECONDARY
HYPERPARATHYROIDISM
;P8 =CBA46=6 4mpaired phosphate excretion
5aised leels o FF23 leads to reduction o
calcitriol leels
;5A;=; :hosphate excretion
6eelamer
calcitriol
ALUMINIUM
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ALUMINIUMINTO,ICATION
4t is characteriJed by acutedementia unresponsie and seereosteomalcia
Bypercalcemia deelops $hen thesepatients are treated $ith itamin
Aluminium is present at the site o
osteoid mineraliJation and calciumincorporation into the seleton isimpaired
MILK ALKALI
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MILK 4 ALKALISYNDROME
4t is due to excessie ingestion ocalcium and absorbable antacidssuch as mil or calcium carbonate
CharacteriJed by hypercalcemiaalalosis renal ailure
Chronic orm o the disease is termed
as /urnettTs syndrome
MILK ALKALI
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MILK 4 ALKALISYNDROME
A cycle o mild hypercalcemiaalalosis
seere hypercalcemia renalCa retention
C C
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B::5CA#C=4A
CA5F
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;BAH 8< VVVV