Calcium & Phosphate

Metabolism

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 regulatedhormonally- 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=??????????????
Acid base disturbance .

( Affect binding to protein .)

Increase when PH increased .
Decrease when PH decreased .

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-OHcholecalciferol(kidney)

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 2 nd
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 calcitonin, 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 role

Hypoparathyroidism:

1.

2.

3.
4.

DiGeorge syndrome: aplasia or hypoplasia of

parathyroid gland.
associated with different anomalies including
cardiac and facial anomaly mainly and also VATER
and CHARGE associations.
X-linked hypoparathyroidism (absent of the gland
that affect boys and appeared with the first 6 months
of age.
AR hypoparathyroidism with dymorphic features:
mutation of parathyroid hormone gene.
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.

Hypomagnesemia by: decrease parathyroid

hormone secretion and by blunting tissue
response to PTH.
Pseudohypoparathyroidism lack of response of
inadequate available PTH.

1.
2.
3.
4.

5.

Decerease Ca, increase phosphorus, decrease Vit D.

Defect in alpha subunit of G proteins (2nd messenger)
Administration of synthetic PTH fail to increase Ca
level or increasing excretion of phosphorus in urine.
There are three types
- Type IA: (Alpright hereditory oasteodystrophy)
- Type IB.
- Type II.
Diagnostic test is by failure to increase CAMP in
urine in response to PTH infusion

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.

2.

Hungry bone syndrome classicaly happen after

parathyroidectomy of hyperparathyroid tumor
(decrease Ca, phosphorus and Mg).
3. 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

Diagnosis
Lab:
Serum Ca: total and ionized.
Serum Mg.
Phosphorus: increase in hypoparathyroidism, renal
failure,
Serum Lytes and glucose mainly in neonate with
seizure .
PTH level in serum:

 Vit

D (1-25 OH vit D and 25 OH vit D

levels).
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 defect and RF

Determination of Ca
Specimen:
serum or lithium heparin plasma

Anticoagulants such as EDTA or oxalate bind Ca very tightly

and interfere with its measurement

Methods: ( For total Ca )

- Photometric Methods
- Atomic Absorption spectrophotometric methods

Corrected [Ca] =
measured [Ca] + 0.02

( 40 [albumin] )

Methods: ( for Free Ca )

Calcium ion-selective electrodes

Phosphate
Physiological function :
80% of the total body phosphate is contained in
bone .
High-energy phosphate bond in ATP
Essential element in

- Phospholipid cell membranes

- Nucleic acids
- Phosphoproteins

Phosphate is critical for activity for several

important enzyme

Regulation:
PTH lowers blood phosphate concentrations by

Increasing renal excretion .

Vitamin D acts to increase phosphate in the blood
due to
- Increase phosphate absorption in the intestine
Increase phosphate reabsorption in the kidney

Clinical Application:
- Hypophosphatemia
- Hyperphosphatemia

Hypophosphatemia

Hypophosphatemia is very common in hospitalized patients

Infusion of dextrose solution
Use of antacids that bind phosphate
Alcohol withdrawal

Hyperphosphatemia
Renal failure : phosphate excretion
Neonates are susceptible to hyperphosphatemia
Increased breakdown of cells
eg: - severe infections - neoplastic disorders

Determination of inorganic phosphorus

Specimen:
serum or lithium heparin plasma
hemolysis should be avoided

Methods:
Formation of an ammonium phosphomolybdate complex measured at 340 nm
- can be reduced to form molybdenum blue (measured at 660 nm)

Thank You