Calcium & Phosphate

Metabolism
BY :Dr Haider Nadhem
Learning Objectives
By the end of this lecture, the students will be able to:

 Describe the content and functions of calcium and phosphate in the body
 Explain ways to balance calcium and phosphate in the body
 Identify the different forms of calcium and phosphate
 Demonstrate conditions affecting calcium form
 Analyse the mechanisms of regulating level of calcium and phosphate in the
body
 Compare and contrast the causes and pathophysiology of calcium and
phosphate disorders
 Apply the approach to diagnose and manage disorders of calcium and
phosphate
Calcium& Phosphate
Content & Functions
Calcium & Phosphate Contents

Calcium Phosphate
Most abundant mineral 25 • Phosphate is a divalent anion
mol (1 kg)
20 %
Soft Tissues ,
Plasma
80% Muscle
9 mmol

99% ECF
22.5 mmol Phosphate Is the major
Intracellular Anion
and shifts between the
intracellular
and extracellular compartments
Calcium & Phosphate Function

Calcium Phosphate
Structural Neuromuscular activity Structural Intra cellular organic
fraction as ATP
• Bone • Control of excitability • Bone
• Teeth • Release of Hydroxyapatite phospholipid in
neurotransmitte cell membrane
r DNA, RNA
• Initiation of
muscular
contraction

In plasma present as either Inorganic Phosphate

and in phospholipids
Enzymatic Signaling ( typically measured in routine blood
test)
• Cofactor for • Intracellular
coagulation second messenger
factors
Calcium& Phosphate
How to balance within body
 Endocrine
system
Food
25 mmol/ 24
h

Absorptio
n Calcium 7.5 mmol/24 h
7/26
6–12
mmol Bon
GI Phosphate e
system

Filte reabsor
r b
Kidne
Faeces
12.5 mmol/ 24 y
h 2.5–7.5 mmol/24
h
 Bone

Calcium Plasma
Forms
How to present in the body
Calcium in Bone
Bone
• osteoid, a collagenous organic matrix,
• inorganic hydrated calcium salts known as
hydroxyapatites
Bone remodeling
• bone resorption (mediated by osteoclasts),
• bone formation (mediated by osteoblasts)

Alkaline phosphatase, secreted by osteoblasts, is essential to the process, probably acting by releasing
phosphate from pyrophosphate.
Calcium in Plasma
• Bound to protein (mainly
albumin)
• Complexed with citrate and
phosphate
• Free ions. (Physiological
Active)
Conditions affect Calcium forms

Albumin Alkalosis
& &
Plasma Plasma
Calcium Calcium
Albumin & Plasma Calcium
Changes in plasma Albumin concentration will affect total calcium
concentration independently of the ionized calcium concentration
leading to possible misinterpretation of results in both
hypoproteinemia and hyperproteinemia states
Corrected Serum Calcium (Adjusted)

[Calcium]corrected = [Calcium (mg/dl)] measured +0.8[4-albumin(g/dl)]

Adjusted calcium (mmol/L) = Total calcium (mmol/L) + 0.02 [40 –albumin (g/L)]
 Alkalosis & Plasma Calcium

• Binding of calcium is pH dependent

H
HCA
Alkalosis ++
CA++ CA++
CA++

Albumin H
CA++ CAH CA++ CA++
++
H
H
CA++ CA++
H

the concentration of free ionized calcium falls, and this may be sufficient to produce clinical symptoms and signs
of hypocalcaemia, although total plasma calcium concentration is unchanged.
Buzz
Groups
Discussion
Case Scenario
72-year-old woman with chronic live disease, recently hospitalization
for pneumonia

Lab investigation:
• Calcium (total) 7.9 mg/dl ( 8.5 – 10.5 mg/dl)
• Albumin 2.5 g/dl (3.5 – 5.0 g/dl)

Do you expect the patient will develop sign and symptoms of

hypocalcemia ?
Calcium-Regulating
Hormones
Calcium-Regulating Hormones

Calcitriol
(1,25- Parathyroid Hormone
dihydroxycholecalciferol).
(PTH)
FGF2 Calcitonin
3 minor role
Parathyroid Hormone
 single-chain polypeptide, (84 amino acids)
 The biological activity of PTH resides in the N-terminal (1–34).

 Stimuli :(ionized) calcium

 Inhibition: hypercalcemia.
Actions of parathyroid hormone (PTH).
• Bone
 rapid release of calcium to ECF mediated
by osteocytes
 longer term response dependent on
the proliferation of osteoclasts.
• Kidney
 PTH increases the fraction of the filtered
load that is reabsorbed.
 PTH promotes Phosphaturia by decreasing
the reabsorption of filtered phosphate
 stimulates the formation of calcitriol
Calcitriol
derived from vitamin D by successive
hydroxylation :
• the liver (25-hydroxylation)
• kidneys (1α-hydroxylation)

Hydroxylation in the liver is not subject to

feedback control, but that in the kidneys is
closely regulated
 Calcitonin Fibroblast growth factor 23
This polypeptide hormone, produced by the C-cells of • FGF23 is a member of the fibroblast
the thyroid, growth factor (FGF) family which is
inhibit osteoclast activity, and thus bone resorption, responsible for phosphate and
vitamin D metabolism.
Stimulated by • FGF23 is secreted by osteocytes
• High Calcium Level in response to elevated calcitriol
• Gut Hormones

Function
• FGF23 decreases the reabsorption
and increases excretion of
phosphate
• suppress 1-alpha-hydroxylase,
reducing its ability to
activate vitamin D
Calciumand phosphate
homeostasis
• Hypocalcemia stimulates the secretion of PTH
• Increase release from bone.
• Increases the production of calcitriol
• Increase uptake of both calcium and phosphate from the gut
• PTH is phosphaturic, so the excess phosphate is excreted
Calciumand phosphate
Calcium Disorders
Hypercalcemia
• hypercalcemia is often clinically silent,

Stones, Bones, Groans, and Psychiatric

overtones
• Stones – Nephrolithiasis
• Bones – Bone Pain
• Groans – Abdominal pain

• Psychiatric overtone – Depression, anxiety,

confusion
Cardiac
Arrythmias
 5 Mechanisms of Hypercalcemia
Vitamin PTH
D Excess
Excessive Excess PT
dietary Calcitriol H -
intake of Ca Calcium
Calcium
+ Phosphat
Phosphat
e
Blood e
Calcium
Phosphate
+
+ PTH
- PTH
Calcitriol
+ +
Calcitriol
Excessive
Calcium Phosphate hormone
Thiazid independen
e t bone
diuretic resorption
s
PTH Excess Hormone independent Vitamin D Excessive
bone resorption Excess Intake

Hyperparathyroidism Osteolytic bone  Intake Milk Alkali

metastases of vitamin syndrome
D

1 Or 3 Paget’ s disease of Ectopic  Intake CaCO3

bone Calcitriol
production

PTH rP secreting Hyperthyroidism i.e. granuloma

Malignancy TB and
lymphoma
 Malignanc 10- 30 % of course of Malignancy
y
Mechanism Typical Associated Cancers

Production of PTH rP
(humoral hypercalcemia of
Lung, breast, Ovarian,
renal
80%
Malginancy

Osteolytic Metastasis Almost All 20 %

(Breast, Lung & Multiple
Myeloma )  transforming growth factors,
 prostaglandins
 osteoclast-activating
cytokines

Ectopic production of Calcitriol Lymphoma 1%

Hyperparathyroidism
Primary
• One case per 1000 persons.
• Parathyroid adenoma, 90 %
• Asymptomatic hypercalcemia
• Increased risk of developing
osteoporosis and renal
impairment,
• Complications (e.G. Calculus
formation, osteoporosis or renal
impairment)
Tertiary
• Autonomous PTH secretion,
• Result of the prolonged
hypocalcemia
stimulus.
• Such hypercalcemia may
manifest for the first time in a
patient given a renal transplant
• Who becomes able to
metabolize vitamin D normally.
 What is
Familial
hypocalciuric
hypercalce
mia??
Hypocalcemia
• Neurological feature: tetany, mental
changes
• Cardiovascular abnormality :
abnormal ECG finding
• Cataract formation
 3 Mechanisms of Hypocalcemia
Vitamin PTH
D Deficiency
Low dietary intake deficienc PT
of Ca Calcitriol y H -
Calcium
Calcium
+ Phosphat
Phosphat
e
Blood e
Calcium
Phosphate
+
+ PTH
- PTH
Calcitriol
+ +
Calcitriol

Calcium Phosphate
Causes
• Hypoparathyroidism
• Vitamin D deficiency
• Renal disease
• Pseudo hypoparathyroidism
• others
Hypoparathyroidism
• Acquired
o Surgery
o Autoimmune
o Idiopathic
o Hemochromatosis
• Congenital form may be associated with thymic aplasia and immune
deficiency,
the DiGeorge syndrome.
Pseudohypoparathyroidism
• resembles hypoparathyroidism, but
plasma concentrations of PTH are
elevated
• There are two types: both are hereditary
disorders
• The effects of PTH are mediated through
the formation of cyclic 3,5-adenosine
monophosphate (cyclic AMP).
Pseudohypoparathyroidism
• In type 1, activation of adenyl cyclase is
defective and cyclic AMP is not formed
in response to the binding of PTH to
its receptor.
• In type 2, cyclic AMP is formed, but the
responses to it are blocked.

The two types can be distinguished by measuring

urinary cyclic AMP after administration of PTH.
Magnesium deficiency
Magnesium is required for both PTH
secretion and its action on target tissues,

Magnesium deficiency can cause

hypocalcemia or render patients insensitive
to the treatment of hypocalcemia with
vitamin D or calcium, or both.
Calciumand phosphate
Phosphate Disorders
Phosphate Disorders
Hyperphosphatemia Hypophosphatemia

• Renal Failure oHyperparathyroidism

• Hypoparathyroidism oCongenital defect in tubular
reabsorption
• Hemolysis
oIngestion of large amount of
antacid
Thank
you