calcium metabolism and hypocalcimia / dental implant courses by Indian dental academy

CALCIUM METABOLISM
AND
HYPOCALCEMIA
INDIAN DENTAL ACADEMY
LEADER IN CONTINUING DENTAL
EDUCATION
www.indiandentalacademy.com

Calcium metabolism
 99% of total body calcium in the bone .
 1% in ICF ,ECF ,& cell membranes .
 Calcium weight is 400mg/kg in infant &
950mg/kg in adult .
 The 1% can be divided in 3 components :
1) 50% ionized . 2) 40% bound to protein .
3)10% complex w/anions{citrate,phosphate,..

Calcium metabolism
 physiologic functions :
1.blood coagulation .
2.muscle contraction .
3.neuromuscular transmission .
4.Skeletal growth & mineralization
 Ionized Ca is physiologically important .

Calcium metabolism
 Serum CA level is determined by net
absorption (GI) & excretion (RENAL).
 Each components is tightly regulated-
hormonally- to keep normal serum level .
 Total CA is usually measured & provides
satisfactory assessment of ionized form .
 However we have exceptions:

Calcium metaolism
 However we have exceptions:
 Decreased serum albumin .
Each 1 g/dl of serum albumin binds about 0.8
mg/dl of calcium .
Cac=Cam+{0.8* decrease in serum
albumin .}
 Acid base disturbance .
( Affect binding to protein .)
Increase when PH increased .
Decrease when PH decreased .www.indiandentalacademy.com

Calcium metabolism
 Calcium regulation :mainly by 3 common
hormones :
1}Parathyroid hormone .
2}Vitamin D .
3}Calcitonin .

Calcium metabolism
Vitamin D
 Vitamin D :provide Ca & PO4 to ECF for bone
mineralization .
 Deficiency in children……..Rickets
 Deficiency in adult……..Osteomalacia
 7-dehydrocholestrol(skin)…cholecalciferol
25-OH- cholecalciferol(liver)…1- 25-OH-
cholecalciferol(kidney)
 MOA: steroid so enter nucleus & bind
receptor that leads to expose part of DNA…
mRNA…Calbindin-D protein in epithlium of
intestine,kidney,..that do the action .

Calcium metabolism
Vitamin D
 Actions:
1)increase Ca absorption from intestine.
2) increase PO4 absorption from intestine.
3) increase renal reabsorption of Ca &PO4.
4) increase bone resorption from old bone
&mineralize new bone{net resorption} .
 Overall effect :increase serum Ca & PO4 .

Calcium metabolism
Vitamin D
 Regulation :
 Ca…..-ve PTH .
 PO4….-ve VIT D .
 VIT D…..-ve PTH .
 VIT D….-ve 25OHD .
 PTH ……+ve VIT .

Calcium metabolism
PTH hormone
 Major hormone in regulation serum Ca .]
 Synthesis & secreted from chief cells of
parathyroid gland .
 MOA :
 polypeptide that binds to specific receptors
{G proteins} that lead to increase 2nd
messenger cAMP that leads to physiologic
actions of the hormone .

Calcium metabolism
PTH hormone
 Actions :
 1)increase bone resorption..increase Ca & PO4
in serum .
 2)increase renal Ca reabsorption .
 3)increase Ca absorption from intestine
indirectly by increase VITD .
 4)decrease PO4 reabsorption from proximal
tubules …increase ionized Ca .
 Overall effect :increase serum Ca & decrease
serumPO4 .

Calcium metabolism
PTH hormone
 Regulation:
 Ca senor proteins that increase PTH when Ca
level decreased & decrease PTH when Ca
level increased .
 PTH increase VIT D level by activation 1-
Ohlase .
 Increase PO4 leads to increase PTH(by
decreasing Ca level ) .
 Mg decrease leads to deacrease PTH level .

Calcium metabolism
Calcitonin
 Is synthesized & secreted by Para follicular cells
of thyroid .
 MOA :1) Peptide that inhibit bone osteoclast
& so inhibit bone resorption .
2)increase renal excetion .
 Increase secretion when Ca level increase .
 Action:decrease CA level .
 Overall effect : decrease serum Ca .

Hypocalcemia
 Causes of hypocalcemia
 Specific causes in neonates
I. Early neonatal hypocalcemia:(within 48-72
hour of birth)
Causes: 1- prematurity: poor intake, decrease
response to Vit. D, increase calcitoni,
decrease albumin.
2- birth asphyxia: delayed
introduction to feed, increase calcitonin,
increased endogenous PO4 load, alkali
therapy.
3- infant of diabetic mother:
functional parahypothyroidism induced by Mg
defficiency has predominant rolewww.indiandentalacademy.com

Spe cific cause s in ne o nate s (co nt. )
4- IUGR: interruption Ca delivery across placenta,
prematurity, asphyxia.
 Serum Ca correlate directly to gestational age.

Spe cific cause s in ne o nate s (co nt. )
II. Late neonatal hypocalcemia: happen from
5 days of birth, may appear till 6 weeks of
age.
 Causes:
1. Exogenous PO4 load, most common due to
high PO4 content in formula, or cows milk and
decreased in GFR contribute also.
2. Mg deficiency.
3. Transient hypoparathyroidism
4. Hypoparathyroidism due to other causes:
(idiopathic, congenital, maternal
hyperparathyroidism, hypomagnesemia)www.indiandentalacademy.com

 Hypoparathyroidism:
1. DiGeorge syndrome: aplasia or hypoplasia of
parathyroid gland.
associated with different anomalies including
cardiac and facial anomaly mainly and also
VATER and CHARGE associations.
2. X-linked hypoparathyroidism (absent of the
gland that affect boys and appeared with the
first 6 months of age.
3. AR hypoparathyroidism with dymorphic
features: mutation of parathyroid hormone
gene.
4. HDR syndrome: AD consist from (nerve
deafness, renal dysplasia, and
hypoparathyroidism)

5. Autoimmune polyglandular syndrome type I: AR,
due to mutation in autoimmune regulator gene
Consist from (hypoparathyroidism, addisson
disease, mucocutaneous candidiasis).
6. Calcium sensor receptor gene mutation.

7. Kearns-Sayre syndrome: mitochondrial inherited
disorder. (ie, external ophthalmoplegia, ataxia,
sensorineural deafness, heart block, and elevated
cerebral spinal fluid [CSF] protein), are associated
with hypoparathyroidism. Hypothyroidism affect
after age of 5 years
8. Hemochromatosis: iron overload
9. Wilson disease: copper overload
10. Postsurgical and irradiational hypoparathyroidism.

 Hypormagnesemia by: decrease
parathyroid hormone secretion and by
blunting tissue response to PTH.
 Pseudohypoparathyroidism lack of
response of inadequate available PTH.
1. Decerease Ca, increase phosphorus, decrease
Vit D.
2. Defect in alpha subunit of G proteins (2nd
messenger)
3. Administration of synthetic PTH fail to increase
Ca level or increasing excretion of phosphorus
in urine.
4. There are three types
- Type IA: (Alpright hereditory oasteodystrophy)
- Type IB.
- Type II. www.indiandentalacademy.com

CONTINUE.. 12.Pseudohypoparathyroidism
 Albright hereditary osteodystrophy
characterized by Short stature, obesity, round
face, short distal phalanges of the thumbs,
brachymetacarpals and brachymetatarsals,
subcutaneous calcifications, dental
hypoplasia, and developmental delay
characterize this phenotype.
 Pseudopseudohypoparathyroidism (PPHP) is
characterized by normal calcium homeostasis
in the setting of the AHO phenotype.

 Vit D defficiency: causes
1. Poor intake
2. Inadequate exposure to UV light
3. Malabsorption (liver disease, GI disease,
pancreatic insufficiency).
4. Increase metabolism (as in anticonvulsant
that activate P450 system enzyme in liver
that increase degradation of vit D.
5. Renal disease: CRF mainly.
6. Vitamin D dependent ricket type 1(AR
absence of one alpha hydroxylase enzyme).
7. Vitamin D dependent ricket type 2(AR defect
in vit D receptor, 50% have alopecia

 Redistribution of plasma Ca:
1. Hyperphosphatemia due to:
 Excessive phosphate intake because of inproper
formula and decreased GFR.
 Loading in TPN.
 Ecessive intake by inappropriate PO4 enema or
laxative.
 Renal failure.
 Increase endogenous phosphorus by anoxia, TLS,
Rhabdomyolysis.
1. Hungry bone syndrome classicaly happen after
parathyroidectomy of hyperparathyroid tumor
(decrease Ca, phosphorus and Mg).
2. Pancreatitis: break down omentum by lipase.

 Citrate in transfused blood products that
causes binding to ionized Ca but normal
total Ca.
 Drugs like thiazide.
 Septic shock and ICU cases: unkown
mechanism

Clinical picture
 Symptoms:
• Related to degree and rate of
hypocalcemia.
• Mild hypocalcemia is asymptomatic.
• Most clinical picture due to neuromuscular
irritability.
• Symptoms can be provoked by
hyperventilation.

• Symptoms depend on the age:
• In neonate: lethargy, vomitting, poor feeding
(sepsis picture), abdominal distention, seizure,
jitterness.
• In children: seizure, muscle cramp, tetany,
larygospasm, parasthesia of perioral and hand
area.
• Others like basal ganglia calcification in PHP,
rikets in vit D deficiency, others depend on
syndrome.
• Arrhythmia

 Physical findings:
• Hyper-reflexia (carpopedal spasm, chvostec
sign- 10-20% nonspecific, trousseau sign,
stridor and cyanosis).
• Abdominal distention.
• Seizure.
• Lethargy.
• Apnea.
• Depend on syndrome (PHP, DiGeorge, …)

Diagnosis
A. History
B. Lab:
 Serum Ca: total and ionized.
 Serum Mg.
 Phosphorus: increase in hypoparathyroidism,
renal failure, others, decrease in vit D deficiency.
 Serum Lytes and glucose mainly in neonate
with seizure .
 PTH level in serum: indicated if hypocalcemia
persist in presence of normal Mg and normal or
increased phosphorus
 Decrease or normal in hypoparathyroidism: PTH
challenge, increase Ca level.
 decrease PTH due to vit D deficiency and PHP, no
increase in Ca when doing PTH challengewww.indiandentalacademy.com

 Vit D (1-25 OH vit D and 25 OH vit D levels).
Poor intake, malabsorption, decrease light
exposure, excessive metabolism cause
decrease in 25 OH and normal or increase or
decrease 1-25 OH.
 Vit D1 rickets cause normal 25 OH and decrease 1-
25 OH.
 Vit D2 rickets causes increase in both of 25 OH and
1-25 OH.
 Decrease PTH causes decrease 1-25 OH
 PHP causes increase 1-25 OH
 Alkaline phosphatase: increase in vit D
defeciency and normal to decrease in
Hypoparathyroidism.
 Total protein, albumin, PH
 KFT
 Urine Ca, Mg, PO4 and Cr in renal tubular

T.CAT.CA I.CaI.Ca PO4PO4 PTHPTH
HYPOALUMEIAHYPOALUMEIA DECDEC NN NN NN
ALKALOSISALKALOSIS NN DECDEC NN N/INCN/INC
VIT D DEFVIT D DEF DECDEC DECDEC DECDEC INCINC
CRFCRF DECDEC DECDEC INCINC INCINC
HYPOPTHHYPOPTH DECDEC DECDEC INCINC DECDEC
PHPPHP DECDEC DECDEC INCINC INCINC
PACREATITISPACREATITIS DECDEC DECDEC N/DECN/DEC INCINC

Radiology
 CXR: loss of thymic shadow in DiGeorge
syndrome and osteopenia in rickets.
 Wrist X-ray: rickets changes.
 Hand X-Ray: in PHP
 Echocardiogram in DiGeorge syndrome there
is cardiac anomaly.
 Brain MRI: basal ganglion calcification in
PHP.
 Renal ultrasonography: Treatment of
hypoparathyroidism can lead to
nephrocalcinosis as a result of calciuria.
Baseline renal ultrasonography with initial
treatment should be performed.

D. Others
A. ECG show prolonged QT interval
B. Malabsorption work up
C. Total lymphocytes

Treatment
 Symptomatic hypocalcemia needs IV calcium and
continuous monitoring for arrhythmias.
 Once serum Ca is in safe range ( >7 mg/dl) IV Ca
can be stopped, and oral Ca started.
 Oral Ca and vit D are initiated as soon as possible
when patient is tolerating oral feed.
 Active form of vit D is preferred in treatment of
HPH or PHP and hyperphosphatemia because
both impair activation of 25 OH vit D by one alpha
hydroxylase.
 Diet, no specific diet is required but adequate Ca
and vit D intake is recommended. (in late neonatal
hypocalcemia low phosphorus formula needed likewww.indiandentalacademy.com

 Calcium, intravenous –
 Calcium gluconate 10% (ie, 100 mg/mL) IV solution
contains 9.8 mg/mL (0.45 mEq/mL) elemental
calcium.
 Calcium chloride 10% (ie, 100 mg/mL) contains 27
mg/mL (1.4 mEq/mL) elemental calcium.
Calcium chloride is more irritating to the veins and
may affect pH; therefore, it is typically avoided in
pediatric patients.
 Dose:
 10-20 mg/kg elemental calcium (1-2 mL calcium
gluconate/kg) IV slowly over 5-10 min to control
seizures; may be continued by 50-75 mg/kg/d IV
infusion over 24 h

 Use extreme care in peripheral infusion because
extravasation can cause severe tissue necrosis.
 rapid IV infusion may cause bradycardia and
hypotension.
 may cause liver necrosis if administered in an
umbilical venous catheter lodged in a branch of portal
vein.
 prolonged use of calcium chloride may lead to
hyperchloremic acidosis

 Calcium glubionate (Neo-Calglucon) -- Calcium
supplement for PO use. The glubionate salt
(1800 mg/5 mL) contains 115 mg elemental
calcium/5 mL.
 Dose: 50-75 mg/kg/d (as elemental calcium) PO
divided q6-8h
 Use with caution in small neonates because of high
osmolar load; may cause diarrhea in older children

 Calcium carbonate (Oystercal, Caltrate,
Tums, Os-Cal)
 Supplement for PO use.
 In many ways, the calcium supplement of choice
because it provides 40% elemental calcium.
 Thus, 1 g of calcium carbonate provides 400 mg of
elemental calcium.
 Well absorbed orally and unlikely to cause
diarrhea.
 Available in tab and liquid forms.
 Dose: -Neonates: 30-150 mg/kg/d PO divided
qid; may be added to formula (eg, Similac PM
60/40 to make a calcium-phosphorous ratio of 4:1)
-Children: 20-65 mg/kg/d PO divided
bid/qid
 Hypercalcemia or hypercalcuria may occur when

 Calcitriol (Rocaltrol) –
 Active metabolic form of vitamin D (ie, 1,25-
dihydroxycholecalciferol).
 Especially useful in impaired liver or renal function
causing inability to hydroxylate vitamin D to its
active forms.
 Generally is rapidly acting.
 however, may act more slowly in neonates (36-48
h). Preterm infants may be resistant to its actions.
 Also used to treat acute hypocalcemia.
 Dose: 0.01-0.05 mcg/kg/d IV qd/bid; adjust dosage
until normocalcemia is attained
 May cause hypercalciuria; give with calcium salts to
attain optimum results; may add
hydrochlorothiazide to regimen to control
hypercalciuria www.indiandentalacademy.com

 Dihydrotachysterol (DHT, Hytakerol) –
 Synthetic analog of vitamin D, which does not
require activation by renal 1 hydroxylase for
activity.
 Also available in liquid form facilitating
administration of variable doses in infants and
young children.
 1 mg equivalent to 120,000 U (ie, 3 mg) vitamin D-
2.
 Dose:
 Neonates: 0.05-0.1 mg/d PO
Children: 0.5-2 mg/d PO
 May cause hypercalciuria; give with calcium salts
to attain optimum results; may add

 Symptomatic hypocalcaemia :
 In neonate: Ca gluconate of 100-200 mg/kg or
1-2ml/kg of 10% conc. Over 5-10 min & can repeated every 6
to 8 hrs , or may continued as continuous infusion of 50-75
mg/kg over 24 hrs .
 In children: Ca gluconate of 100-200 mg/kg or
1-2ml/kg of 10% conc. Over 5-10 min & can repeated every 6
to 8 hrs
*The above medication should administered under cardiac
monitoring .
 Once symptoms resolved oral Ca used to
correct serum level ,& Ca level should kept
below half normal range of Ca
 Tapering of oral dose depends on serum Ca
level .

 Ca supplement with food binds PO4 insid
intestine so can decrease PO4 level when
used in TLS,CRF,hypoPTH .
 Ca supplement between meals prevent
decrease PO4so used when we have low
Ca & PO4 .
 Vit D used in:
 Malsbsorption, poor intake, and increase
metabolism with Ca supplements.
 Children with CRF, HPT, PHP, and vit D1
rickets as a primary treatment

Further Outpatient Care:
 Carefully monitor medication dose and serum
calcium concentrations. Therapeutic goal is to
maintain serum calcium in the low-normal
range to decrease risk for nephrocalcinosis.
 Perform periodic renal ultrasonographic
studies to assess for nephrocalcinosis
development

Certain Situations
 In pacreatitis and rhabdomyolysis complete
correction of hypocalcemia should be avoided
because with resolution of the primary
problem there is release of the complexed Ca
and hypercalcemia may happen.
 If acidemia is present hypocalcemia should if
possible be corrected first, acidemia increases
the ionized Ca concentration by displacing Ca
from albumin, so the correction of acidemia
causes the ionized Ca concentration to
decrease.
 In hypomagnesemia Mg should be corrected
first www.indiandentalacademy.com

Medical/Legal Pitfalls:
 Intravenous infusion with calcium-containing
solutions can cause severe tissue necrosis.
 Failure to distinguish calcium receptor defects
from hypoparathyroidism
 Failure to consider an associated cardiac
lesion in an infant with hypocalcemia
 Failure to monitor serum calcium
concentrations for at least 24 hours after
intravenous calcium withdrawal (Rebound
hypocalcaemia can occur when intravenous
calcium is withdrawn, even on adequate
amounts of oral calcium.)

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