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CALCIUM AND

PHOSPHORUS
MINERAL AND BONE
METABOLISM
 Skeleton undergoes
continuous remodeling
 Maintain skeleton
integrity
 Metabolic functions –
storage of Ca and P
 Net balance :
 Bone mineral deposition
and resorption
 Intestinal absorption
 Renal excretion
MINERAL AND BONE
METABOLISM
 PRINCIPAL HORMONES:
 Parathyroid hormones
 Calcitonin
 1,25 dihydroxy vitamin D
MINERAL AND BONE
METABOLISM
 Bone – Ca, P,
inorganic matrix
(collagen)
 Types of Bone
1. Cortical or compact
bone – 80%
2. Cancellous or
trabecular bone –
20%
- Large surface area for
short term mineral
exchange
MINERAL AND BONE
METABOLISM
 Osteoclasts – resorb bone
 Osteoblasts – synthesize and
control mineralization of organic
matrix
MINERAL AND BONE
METABOLISM
 Bone metabolism reflects the
body’s efforts to maintain serum
calcium and phosphorus levels
CALCIUM
 5th most common element
 Most prevalent cation
 1-1.3 kg
 99% hydroxyapatite in skeleton
 1% ECF and soft tissues
CALCIUM
3 forms:
2. Free or ionized calcium - 50%
3. Complex calcium-bound to anions
(bicarbonates, lactate, phosphates)-10%
4. Plasma protein-bound calcium - 40%

 Distribution altered by pH changes in ECF


and plasma protein changes
e.g. alkalosis - ↑ protein binding - ↓ free Ca;

acidosis - ↓ protein binding - ↑ free Ca


CALCIUM
Functions:
 Skeletal mineralization
 Blood coagulation
 Neural transmission
 Plasma buffering capacity
 Enzyme activity
 Normal muscle tone, excitability of
skeletal and cardiac muscle
 Glandular synthesis, regulation of glands
 Preserve cell membrane integrity and
permeability
CALCIUM
Average dietary intake: 600 – 800
mg/day
Post menopausal, lactating: 1500
mg/day

 Only half is absorbed in adults –


duodenum and upper jejunum by
active transport
CALCIUM
Loss: majority in urinary excretion
sweat

Urinary excretion increased in :


 Hypercalcemia
 Acidosis
 Glucocorticoids

Decreased excretion:
 PTH
 Certain diuretics
 Vit D
CALCIUM
Homeostasis
 Ionized calcium = 1.25 umol/L
 Primary determinant of hormonal
influences – PTH, 1,25 (OH)2 D3 ,
calcitonin
CALCIUM
 Total calcium measurements: protein
bound and ionized calcium
 Falsely low total Ca in
hypoalbuminemia
CALCIUM

3 common methods
1. Colorimetric analysis w/
metallochromic indicators
2. Atomic absorption spectrometry (AAS)
– reference method
3. Indirect potentiometry
CALCIUM
Reference Interval:
Total Ca = 8.8 – 10.3 mg/dl (2.2 – 2.58
mmol/L)
Serum – preferred specimen

Ionized (free) Ca = 4.6 – 5.3 mg/dl (1.16-


1.32 mmol/L)
Whole blood, heparinized, serum
Anaerobic, transport on ice, stored 4oc
Causes of Hypercalcemia

PTH mediated
Primary hyperparathyroidism (most common):
Sporadic
Multiple endocrine neoplasia (types 1 and 2)
Familial hypocalciuric hypercalcemia
Ectopic secretion of PTH by neoplasms (rare)?
Non - PTH mediated
Malignancy associated (most common)
Vitamin D mediated:
  Vitamin D intoxication
  Increased generation of 1,25(OH)2D/
Other endocrinopathies:
  Thyrotoxicosis
  Hypoadrenalism
Immobilization with increased bone turnover
Milk–alkali syndrome
Sarcoidosis
Multiple myeloma
Causes of Hypocalcemia

PTH mediated
PTH deficiency:
  Permanent:
    Acquired:
      Postsurgical(/L3)
    Hereditary:
      Idiopathic hypoparathyroidism
      DiGeorge syndrome (branchial dysgenesis)
      Polyglandular autoimmune syndromes
  Reversible:
    Severe hypomagnesemia
  Longstanding hypercalcemia
PTH resistance:
  Pseudohypoparathyroidis

Vitamin D mediated
Vitamin D deficiency
25(OH)D deficiency
1,25(OH)2 deficiency:
  Reversible inhibition of 1-hydroxylase
  Intrinsic renal defects (chronic renal failure, tubulopathies, Fanconi's
syndrome)
Defective response to 1,25(OH)2D
PHOSPHORUS
 Total body phosphorus = 700-800
gm
 80-85% skeleton – inorganic – Ca
phosphate, hydroxyapatite
 15% - ECF
 Intracellular – organic phosphates –
phospholipids, nucleic acids, ATP
PHOSPHORUS

Homeostasis:
 Diet – 800 – 1400 mg

 Bone metabolism

 60-80% absorbed in gut – passive

and active transport


 Freely filtered in glomerulus
PHOSPHORUS
 Blood – 12 mg/dL
 RBC – organic phosphates

 Plasma – inorganic phosphates –

divalent and monovalent buffers


 pH dependent
PHOSPHORUS
 10% serum phosphorus protein
bound
 35% complexed w/ Na, Ca, Mg
 55% free

 Inorganic phosphates are measured


in routine clinical settings
PHOSPHORUS
Functions:
 Skeleton
 Intra and extracellular functions
 Nucleic acids
 Phospholipids, phosphoproteins
 ATP, NADP
 Intermediary metabolism and enzyme
systems
 Normal muscle contractility, neurologic
function, electrolyte transport, O2 carrying
capacity by hemoglobin (2,3 DPG)
PHOSPHORUS
Homeostasis:
 Diet – 800 – 1400 mg

 Bone metabolism

 60-80% absorbed in gut – passive and

active transport
 Freely filtered in glomerulus

 80% reabsorbed prox tubules


PHOSPHORUS
Homeostasis:
 PTH – dec serum phosphate

 Vit D and growth hormone – inc serum

phosphate
PHOSPHORUS
Analytical Techniques:
2. Direct UV measurement of colorless
unreduced complex
3. Use reducing agents – molybdenum blue
4. Enzymatic methods

 Serum
 Fasting morning specimen
PHOSPHORUS
Analytical Techniques:

 Increased in prolonged storage,


hemolysis
PHOSPHORUS
Reference Interval:

Adults: 2.8 – 4.5 mg/dl (0.89 – 1.44 mmol/L)


Children: 4 -7 mg/dl ( 1.29 – 2.26 mmol/L)
Causes of Abnormal Phosphate Levels

Elevated
Hypoparathyroidism and
pseudohypoparathyroidism
Renal failure
Hypervitaminosis D
Cytolysis
Pyloric obstruction
Decreased
Alcohol abuse
Primary hyperparathyroidism
Acute respiratory alkalosis
Myxedema
Exogenous/endogenous steroids
Diuretic therapy
Renal tubular defects
Oncogenic phosphaturia
Diabetic coma
Thank You

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