DrFIranmanesh CalciumPhysiologic chemistry Distribution 5 th most common element Most prevalent cation in the body Healthy adult contain 113kg of calcim99 in the form of hydroxyapatite1 in ECF amp Soft tissue ID: 776650
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Slide1
Mineral and bone metabolism
Dr.F.Iranmanesh
Slide2Slide3Calcium,Physiologic chemistry
Distribution:
5
th
most common element
Most prevalent
cation
in the body
Healthy adult contain 1-1.3kg of calcim,99% in the form of hydroxyapatite,1% in ECF & Soft tissue
Serum(Plasma) calcium exists in three forms:
1:Free(Ionized) #50%
2:Complex with anions #10%
3:Bound to plasma proteins#40%,Mostly Albumin,80%
Slide4Calcium binds to negatively Charged sites of proteins ,so dependent to PH & Protein
cncentration
.
Alkalosis :↑ binding so decreased free ca.
Acidosis : ↓Binding so Increased free ca.
[Ca++][pr--]/[
Capr
]=ĸ
Hostings
&Mclean 1939
[Ca++]=ĸ[pr--]/[
Capr
]
Slide5Calcium Function
mineralization
Blood coagulation
Neural transmission
Maintenance of normal tone and
excitabilityof
Skeletal and cardiac muscle.
Glandular synthesis and regulation of exocrine & endocrine glands.
Preservation of cell membrane integrity and permeability.
Slide6Calcium intake
Average dietary Intake : 600-800mg/Day
Recommended 1200 mg during
preg
.& Lactation and 800-1200 mg during childhood.
Ca absorption : Active transport in Duodenum and upper jejunum.(50%)
Increased in pregnancy, lactation and rapid growth and decreased with advanced ages.
Major stimulus of ca. absorption
is vitamin D.
Slide7Absorption enhanced by Growth
hormone,acid
medium,incresed
protein intake.
Decreased
with:Ca
/
phos
ratio >2
Phytic
acid,Oxalate,Fatty
acids,Cortisol
,
Excessive alkalinity of intestinal contents.
Slide8Ca Excretion
Sweath:15-100mg/day
Major
loss:Urine
100-200mg/day
Wide variation in intake has little effect on
U.Excretion
Enhanced by:
Acidosis,hypercalcemia,phosphate
deprivation and
glucocorticoids
.
Decresedby
PTH,Diuretics,VitaminD
Slide9ECF
Kidney
Parathyroid
Bone
Liver
Thyroid c cells
Intestine
Hypocalemia
PTH
255
Hyper ca
Phosphorus
Urine
PTH
Ca++
Ca++
25-OH-D3
1,25(OH)2D3
Ca++
1,25(OH)2D3
Calcitonin
Calcium Homeostasis
Slide10Slide11Slide12Analytical techniques :Total Calcium
Clark and
collip
method
Today 3 methods:
1)Colorimetric analysis
2)Atomic absorption spectrometry(AAS)
3)Indirect
Potentiometry
Slide13Colorimetric
Metallochromatic
indicators:
O-
Cresolphthalein
complexon
(CPC)
Red color in alkaline solution.
Measured at 580nm.
Addition of 8 -
hydroxyquinolone
:↓Mg.
Arsenazo
III ,Ca-indicator complex:
Measured at 650nm
High specificity at slightly acidic PH
Hemolysis
,
lipemia,icterus,paraproteins
and Mg
intrfere
with colorimetric methods.
Slide14Calcein
forms fluorescent complex
Stimulates at 490nm & emits at 590nm
Titration of complex with EDTA
AAS is the reference method
Dilution with Lanthanum hydrochloride to reduce viscosity and interference
from proteins and organic and inorganic ions.
Ind.Potentiometry:An
electrode selective for
ca.measures
a sample that is also measured against a Na selective electrode.
Slide15Analytical techniquesIonized calcium
Ion selective electrodes(ISE)
Accurate,precise,automatic
determination of ionized(Free)Ca.
Consists of a membrane separating a reference solution (CaCl2,AgCl)and a reference electrode(Ag/
AgCl
or calomel) from the solution to be analyzed.
Slide16Reference intervalsTotal calcium
Total ca. in adults 8.8-10.3mg/dl(2.20-2.58mmol/L)
Serum is the preferred Specimen
Heparinized
plasma is also acceptable.
Citrate,Oxalate,EDTA
interfere with commonly used methods.
Hemolysis
,
icterus,lipemia,paraproteins
and Mg interfere with colorimetric methods.
Total
ca.corrected
for
hypoalbuminemia
=total ca(measured)+
[(Normal Albumin-
patient,sAlb
.)x0.8]
Normal albumin=4.4
Slide17Reference intervalIonized calcium
4.6-5.3mg/dl(1.16-1.32
mmol
/L)
Whole
blood,Heparinized
plasma or serum are acceptable.
Specimens should be collected
anaerbically
and transported on ice and stored at 4⁰C to prevent loss of CO2 and
glycolysis
and stabilize PH.
Slide18Reference interval Urinary calcium
Varies with diet
Average 300mg/day
Urine collection with appropriate acidification to prevent calcium salt precipitation.(15 ml hydrochloric acid)
Slide19PhosphorusPhysiologic chemistry
Adult body content :700mg
85% in Skeleton(Inorganic),15% in ECF & soft tissue(Organic)
In
blood,Plasma
(Inorganic) ,cells (Organic)
In serum ratio of H2PO4-:HPO4-- is pH dependent.
1:1 in acidosis,1:4 in pH 7.4,1:9 in alkalosis.
Serum phosphorus 10% bound to proteins,35% complex with
Na,calcium;Mg
and 55% free.
Only inorganic
ph.is
measured in routine.
Slide20Function
Skeleton
Intra & extracellular role.
Nucleic
acid,phospholipid,phosphoproteins
ATP and
NADP.In
various enzyme systems(
Adenylate
cyclase
)
Essential for normal muscle
contractility,Neurologic
function,Electrolyte
transport and oxygen carrying by
Hb
.
Slide21Phosphorus homeostasis
Present in virtually all foods.
Average dietary intake 800- 1400 mg/day.
60% -80% of intake is absorbed mainly by passive
transport.Active
transport stimulated by 1.25(OH)2D3
Freely filtered in
glomerulus
.
>80% reabsorbed in proximal tubule and smaller in distal tubule.
Proximal transport:(Na-P
cotransport
)mainly regulated by
ph.intake
and PTH.
PTH inhibits Na-P
Cotransport
and causes
phsphaturia
.
Slide22Reference intervals
Adults:2.8-4.5 mg/dl(0.89-1.44
mmol
/L)
Higher in growing children(4.0-7.0)
Serum phosphate has DIURNAL VARIATION.
Higer
levels in afternoon and evenings.
Best measured in FASTING MORNING.
Levels are influenced by dietary
intake,meals,and
exercise.
Slide23Analytical techniques
Reaction of inorganic phosphate with ammonium
molibdate
to form
phosphomolibdate
complex measured at 340 nm in
autoanalyzers
.
Complex can be reduced to form
molibdenum
blue measured at 600 to 700 nm.
Enzymatic methods.
Serum is preferred.
Most anticoagulants(Except heparin) interfere
Prolonged storage with cells at room temperature causes
↑Ph.
Hemolyzed
specimens are Unacceptable (RBC organic esters
hydrolize
to inorganic phosphate during storage.)
Slide24Slide25Disorders of mineral metabolismHypercalcemia
↑Serum ca is associated with:
Anorexia,Nausea,vomiting,Constipation,hypotonia
,
depression,high
voltage T waves on
ECG,lethargy,coma
Persistent
hyperca
. Causes ectopic deposition of ca(
vessels,connective
tissue ad joints ,gastric
mucosa,kidney
)
Most common
causes:Primary
hyperpara,Malignancy
Others :Renal
Failure,Diuretics,Endocrine
disorderes,Vitamin
A and D
intoxication,Lithium
therapy,Milk
alkali
synd.,immobilization,Hyperthyroidism,familial
hypercalciuric
hypercalcemia
.
Slide26Primary Hyperparathyroidism(PHPT)
↑↑PTH in the absence of an appropriate physiologic stimulus causing generalized disorder of
Ca,Ph,Bone
metabolism.
100,000 case/Year in USA
F/M : 2/1
Majority caused by solitary parathyroid adenoma.
Others:Multiple
adenoma,Hyperplasia
,Rarely carcinoma.
↑
Ca,↓Phosphate,Mild
acidosis(↓Renal Bicarbonate
reabsorption
)
↑Ca due to :1)Direct action PTH on
Bone,increased
resorption.2)PTH activated renal
reabsorption
3)PTH stimulated increased renal biosynthesis of 1,25(OH)2D3 which increases intestinal calcium absorption
½ or more
are asymptomatic.
Slide27Hyperparathyroidism
PHPT:Sporadic
MEN1 (Pituitary &pancreas
tumors,Zollinger
Ellison synd.)MEN2A(
Pheo
. &
Medullary
CA of thyroid.)
Secondary Hyperparathyroidism:
Resistance to PTH: RF,VIT D
deficincy
,
Low to normal
Ca,High
phosphate.
Renal
osteodistrophy
Slide28Malignancy :the most frequent cause of
Hpercalcemia
in the hospital inpatient population.
Malignancy associated
hypercalcemia
:
With and without bony metastasis.
With
B.M:Hemathologic
(Multiple
Myeloma,Lymphoma,lukemia
)
breast,Lung,others
Osteoclast
activating
factor,tumor
necrosis factor,IL1
Without
B.M:Humoral
hypercalcemia
of malignancy;
Renal,hepatic,epidermoid
of
head,neck,lung
and
ilet
cell of pancreas…PTH-
rP
↑Urinary CAMP excretion + ↓ or normal PTH
Slide29Vitamin D intoxication
Granulomatous
disorders(
Sarcoidosis
)
Milk alkali syndrome(
↓
Serumca,
↓U.ca,Azotemia,Alkalosis
)
Lab tests in diff DX of
hypercalcemia
:
Serum total & Ionized ca. ,Urine ca.
Serum &urine phosphorus
Alkaline
phospatase,Albumin,PTH
,PTH-
rP,Urine
CAMP
VitaminD,cortisol,GH
,…
Slide30Magnesium
4th most abundant
cation
in the body(after
Na,K,Ca
)
2
nd
most prevalent intracellular
cation
.
Normal body content:1000mmol (22.66mg)
50-60% in Bone,40-50% in soft tissue.
1/3 skeletal Mg is
exchangeable.Reservoir
for extracellular Mg(1% of total body Mg)
Serum:55% Ionized(Mg2+),15%complex with
phosphate,citrate
,…,30% protein bound(Albumin)
45% of TB Mg, is intracellular.(ATP,Nucleus,mith0chondria;RE)
Slide31Function,Mg
Essential for >300 cellular Enzymes.
(Transfer of phosphate
groups,DNA
replication ,
transcription,RNA
translation,ATP
)
Cellular energy
metabolism,Membrane,nerve
conduction,Cardiac
muscle(K pump)
↓Mg after cardiac
Surgury,causes
refractory plasma electrolyte abnormalities(K)and
arrythmia
Slide32Mg
GI
absorption,Renal
Excretion
MG:diatery
intake:300-350 mg/day
Sturable
transport system and passive diffusion
Renal excretion:120-140 mg/24hour
Thick ascending loop of
henle
(60-70%)
Distal tubule(10%),Major regulation site.
Mg2+ the most important regulator.(
PTH,Calcitonin,glucagon
,…)
Slide33Analytical techniques
Serum is preferred over plasma.
Anticoagulants interfere.
Methods:
AAS,Reference
method(remove of ph. With lanthanum)
Photometric
methods,Routine,Metallochromatic
indicators(
Calmagite:collor
in Alk.sol.520nm)
Ionized(Free)
Mg:ISE
(Neutral
ionophores
selective for Mg2+)Interference with ca.
Slide34Reference interval,Mg
Total Mg:1.7-2.2mg/dl(0.75-0.95
mmol
/L)
No age or sex difference in total Mg concentration.
CSF Mg:2.0-2.7mg/dl
Ionized Mg:0.44-0.60
mmol
/L
Slide35Thank you for your attention