Calcium and Phosphorus Metabolism

Competency Table by NMC for CBME

S.N Competency Title Domain Level Core TLM Assessment Vertical Horizontal
o Number integration integration
1. BI 6.10 * K KH Y Lecture Written/ General
, SGD viva voce medicine
* Enumerate and describe the disorders associated with mineral metabolism

Minerals:
Essential for normal growth and maintenance of the body
• Major elements- requirement > 100mg/day
• Minor elements (also called Micro elements or Trace elements) - requirement <
100mg/day
 MICROELE
MENTS
(Minor
Elements)

Iron
Iodin
e
Copp
er
Mang
MACROMINERA
LS anes
(Major
e
Elements)
Zinc
Calcium Moly
Phosphor bden
us um
Magnesiu Sele
m nium
 Sodium Fluor
Chloride ide
CALCIUM
sulfur
Most abundant mineral in body
Mainly an extracellular cation
99% in skeleton and teeth, 1% in soft tissue, <0.2 % in ECF
Contributes to hardness of teeth and bones
Sources of Calcium
Major Source: Cow milk (100mg/100ml), Drum stick leaves
Moderate Source: Egg, Fish, Vegetables
Poor Source: Cereals
Daily Requirement:
- Adult: 500mg/day
- Child: 1200mg/day
- Pregnant & Lactation: 1500mg/day
Absorption of Calcium:
Absorbed at Ist and IInd part of duodenum
Absorption requires a carrier protein called calbindin
Absorbed against a concentration gradient & requires energy (helped by Ca dependant ATPase)
Factors that increase Ca absorption:
Vit-D (calcitriol) à Calbindin à absorption of Ca
Parathyroid hormone (PTH)
Acidity and aminoacids (lysine & arginine) increases Ca absorption
Factors that decrease Ca absorption:
Phytates, Oxalates, phosphate, malabsorption syndromes

FUNCTIONS OF CALCIUM
Physical strength
Bone matrix contain type I collagen 90 % and major protein
Crystals of hydroxyapatite is found within and between collagen
The calcium also present as calcium phosphate and calcium carbonate
Bone serves as a prime reservoir of body Ca++.
700 mg of Ca++ may leave or enter the bones each day
Role of Calcium:
Formation of bone and teeth
Blood clotting (factor IV)
Muscle excitation & contraction of muscle fibers
Transmission of nerve impulse (release of neurotransmitters from presynaptic vesicles)
Release of hormones (insulin, PTH, calcitonin, vasopressin)
Activation of Enzymes
Act as secondary messenger
Decreases capillary permeability
Calcium dependant Enzymes / Proteins
Pancreatic amylase, Trypsinogen, Succinate dehydrogenase, ATPase, Phospholipase-C, Protein
kinase-C, etc.
Calmodulin and Troponin
Enzymes mediated by Ca-calmodulin:
Glycogen synthase, pyruvate carboxylase, pyruvate dehydrogenase, pyruvate kinase
Calcium level in blood:
Total Ca level in blood: 9 – 11 mg/dl
Ionized Ca (free Ca): 5 mg/dl (metabolically active)
About 1 mg/dl of Ca complexed with P & HCO3, but easily diffusible
About 4 mg/dl of Ca complexed with Protein (non diffusible)

Calcium excreted in feces : 150 mg / day

in urine : 300 – 400 mg / day
Methods to Estimate Calcium:
Photometry (Arsenazo method, O-cresolphthalein complexone method)
Ion Selective electrode
Atomic absorption spectrophotometry

Factors regulating blood calcium level:

Actions of Calcitriol (active form of vit-D):
- Promotes absorption of Ca & P from the intestine
- Increases reabsorption of Ca & P from renal tubules
- Increases osteoblastic activity – bone formation
Vitamin D is activated to calcitriol passes into the cytoplasm of intestinal cells and binds with
receptor and pass through nucleus
It causes transcription of gene to form mRNA. mRNA in turn synthesis calbindin protein in the
cytoplasm
Calbindin binds with calcium, transports across the membrane and secreted into the serum. This
is energy dependent active process.
Factors regulating blood calcium level:
Actions of PTH:
Stimulates 1-hydroxylation of 25-hydroxycalciferol in kidney
Increases reabsorption of Ca in kidney,
Causes demineralization of bone
Actions of Calcitonin
Increased Ca stimulates calcitonin secretion from parafollicular cells of thyroid gland
Calcitonin decreases serum Ca level
Inhibits resorption of bone
Antagonizes PTH activity
Calbindin
Intracellular proteins that bind to Ca2+ with high affinity.
However the rate of binding is slow.
Present in intestine, kidney, brain, uterus in mammals.
Regulated by 1,25 (OH)2 D
Functions:
Act as cytosolic calcium buffers
Interacts and activates apical Ca2+-ATPase

Other Factors Influencing Serum Calcium

Phosphorous:
Calcium and phosphorous have a reciprocal relationship.
In renal insufficiency, phosphorous excretion is diminished causing a rise in blood phosphate
level and a consequent fall in blood calcium levels.
Serum Proteins:
Total calcium is decreased in hypoalbuminemia.
0.8 mg/dl calcium is decreased for each gm/dl of albumin.
Blood pH:
Alkalosis favors the binding of free calcium to proteins thereby decreasing the levels of
ionized calcium in the blood.

HOMEOSTASIS OF CALCIUM IN SERUM

Normal serum calcium : 9 – 11 mg / dl
PTH, Calcitriol, Calcitonin are regulators
Thyroxine, GH, Estrogen play minor role
Calcitonin antagonist to PTH
It decrease calcium by decreasing osteoclastic acitivity
Target tissues of PTH are bone, kidney and small intestine

Disorders of Calcium Metabolism

Abnormalities in serum calcium levels
Hypercalcemia: Calcium level >11.5mg/dl
Hypocalcemia: Calcium level<8.5mg/dl
Bone mineralisation and demineralisation
Osteoporosis
Rickets and Osteomalacia
Causes of Hypercalcemia (> 11 mg/dl)
Hyperparathyroidism
Multiple myeloma
Paget’s disease, Carcinoma of bone
Thyrotoxicosis
Tuberculosis, Leprosy
Acidosis
Prolonged immobilization
Drugs: Thiazide diuretics, Excess Vit-D, etc
Clinical manifestations of Hypercalcemia
Anorexia, nausea, vomiting
Polyuria, polydypsia
Confusion, depression, psychosis
Renal stones
Ectopic calcification and pancreatitis
Blood ALP is increased
Causes of Hypocalcemia (< 8.8 mg/dl)
Vit-D deficiency (causes of Vit-D deficiency)
Hypoalbuminemia
Renal failure (Proteinuria & inc. P level)
Nephrotic syndrome
Alkalosis
Hypoparathyroidism & Pseudohypoparathyroidism
Increased Calcitonin (medullary carcinoma of thyroid)
Malabsorption
Trousseau sign:
A blood pressure cuff is inflated to a pressure above the patients systolic level.
Pressure is continued for several minutes.
Carpopedal spasm:
* flexion at the wrist
* flexion at the MP joints
* extension of the IP joints
* adduction thumbs/fingers
Osteoporosis:
At the age of 40 -50 Ca absorption is reduced and calcium excretion is increased.
Demineralization of bone occurs
Reduced bone strength and increased risk of fracture
Reduced level of androgen and estrogen
Decreased absorption of Vit-D
Osteoporosis:
Disease of Bone Growth & Calcium Metabolism
Bone reabsorption exceeds deposition
Osteoclasts mobilize Ca2+ to plasma
Factors: inadequate Ca2+ intake, genes, hormones, smoking
Markers of Bone diseases:
Serum Ca, P, Mg
Urinary excretion of Ca & P
serum ALP & ACP
Vit- D and PTH estimation
PHOSPHORUS

Body phosphate – 1 kg
85% - bone and teeth
15 % - soft tissue, muscles
<0.1% in ECF
Mainly intracellular
Present in all cells
Requirement and sources
500 mg/day
Good source – milk
Moderate source – cereals, nuts & meat
Functions of phosphate ions
Formation of bone & teeth
Production of high energy po4 compounds – ATP etc
Synthesis of co enzymes – NAD, NADP
DNA ,RNA sythesis
Formation of phosphate esters - phospholipids
Formation of phosphoproteins
Activation of enzymes
Maintains blood pH – phosphate buffer
Phosphorus level
Serum 3-4 mg/dl - adults
5 -6 mg/dl - children
Whole blood 40 mg/dl
Hemolysed sample to be avoided
Regulation
Vit-D increases Phosphorus absorption & reabsorption

PTH –
- Increases Phosphorus release from bone
- Increases Phosphorus excretion in urine

Renal threshold – 2mg/dl

Excretion influenced by – muscle mass, renal function & age

Hyper phosphatemia - causes Hypo phosphatemia - causes

1. Increased absorption of po4 1. Decreased absorption of po4

Excess vit D vit D deficiency
Phosphate infusion Mal nutrition
2. Increased cell lysis Malabsorption
chemotherapy chronic diarrhea
bone secondaries 2. Increased excretion
rhabdomyolysis Hyperparathyroidism
3. Decreased excretion Fanconi syndrome
renal impairement Hypophosphatemic rickets
Hypoparathyroidism 3. Hypercalcemia
4. Hypocalcemia 4. Chronic alcoholism
5. Massive blood transfusion 5.Drugs – antacids, diuretics
6. Drugs – furosemide, nifedipine

Methods to Estimate phosphate:

Photometry
 Atomic absorption spectrophotometry

Calcium Vs Phosphorus
Ca has reciprocal relationship with phosphorus
Increased Ca level decreases P level and vice versa
The ionic product of Ca and P in serum is kept at constant
Ca level X P level = 40