CALCIUM AND
PHOSPHORUS
DR SUNIL KUMAR NANDA
PROFSSOR AND HEAD
DEPARTMENT OF BIOCHEMISTRY
1 PIMS
INDICATIONS OF MEASURING SERUM
CALCIUM LEVELS
1. Neurological symptoms, irritability, seizures
2. Renal calculi
3. Ectopic calcification
4. Suspected malignancies
5. Polyuria and polydypsia
6. Chronic renal failure
7. Prolonged drug treatment, which may cause
hypercalcemia (Vitamin D, thiazide diuretics).
2
CALCIUM
Total body Calcium : 1 to 1.5 KG, 99% present in
bone
Sources:
Milk- good source
Egg, fish, vegetables- moderate source
Cereals- small amount
Requirement:
Adult- 500 mg/day
Pregnancy and lactation- 1500 mg/day
children- 1200mg/day 3
CALCIUM- ABSORPTION
Takes place from first and second part of
duodenum
Against conc. Gradient, require carrier protein-
calbindin.
Vitamin D (calcitriol) induces synthesis of
Calbindin in the intestinal cells increased Ca
absorption
Parathyroid hormones - ↑Ca transport from
intestinal cells by increasing activity of 1 alpha
hydroxylase
Acidity, amino acids- lysine, arginine increase
calcium absorption 4
C= CALCITRIOL; CR = CALCITRIOL
RECEPTOR COMPLEX; CB = CALBINDIN
5
FACTORS DECREASING CALCIUM
ABSORPTION
Phytate
Oxalate
Phosphate (The optimum ratio of calcium to
phosphorus which allows maximum absorption is 1:2 to
2:1 as present in milk)
Malabsorption syndrome- ↓
absorption
6
CALCIUM- FUNCTIONS
Activation of enzymes- Calmodulin is a Ca
binding regulatory protein- binds 4 Ca ions
activation of enzymes.
Eg. Adenylyl cyclase, Phospholipase C, Glycogen
synthase, myosin kinase.
Enzymes directly activated by Ca2+: Pancreatic
lipase
7
8
Nerve conduction- transmission of nerve
impulses from presynaptic to post-synaptic
region
Muscle contraction- mediates excitation and
contraction of muscles by interaction with
troponin C increases interaction of actin and
myosin
9
Hormone secretion- mediates secretion of
insulin, calcitonin, parathyroid hormone
Second messenger- Eg. Glucagon
Vascular
permeability- decreases passage of
serum through capillaries
10
Coagulation- factor IV in blood coagulation
cascade.
Myocardium- prolongs systole. Hypercalcemia-
heart stops in systole
Bone and teeth- Bulk quantity used for bone
and teeth formation. Bones are reservoir of
calcium in the body. Osteoblasts- bone
deposition, osteoclasts- bone demineralisation
11
CALCIUM IN BLOOD
Normal blood level- 9 - 11 mg/dl.
Effectivecontrols are present to maintain this
narrow range of blood calcium
12
FACTORS REGULATING BLOOD CALCIUM
LEVELS
Vitamin D
Parathyroid hormone
Calcitonin
Phosphorus
Serum proteins
Acidosis and alkalosis
kidney threshold
13
REGULATION- BLOOD
CALCIUM
Role of Vit D (Calcitriol)
Promotes absorption of calcium and phosphorus
from the intestine by increasing synthesis of
the protein calbindin elevation of blood Ca
Inbone, increases the no. of osteoblasts,
leading to bone mineralization.
Inrenal tubules, increases the reabsorption of
calcium and phosphorus. 14
Role of parathyroid hormone:
PTH increases serum calcium level.
In bone, PTH causes demineralization and
osteoclast increase increase Ca into blood.
Inkidney, PTH decreases renal excretion of
Ca and increased excretion of phosphates.
Inintestine, stimulates calcitriol production
15
increases Ca absorption from kidney.
Role of Calcitonin:
Secreted by thyroid parafollicular cells.
Decreases serum calcium level by decreasing
bone resorption
In kidney, promotes phosphorus excretion.
Calcitonin,
calcitriol and PTH act together to
maintain blood calcium
16
17
18
VITAMIN D PTH CALCITONIN
Blood calcium Increases Drastically Decreases
increases
Main action Absorption Demineralization Opposes
from gut demineralization
Calcium Increases Increases -
absorption (indirect)
from gut
Bone resorption Decreases Increases Decreases
Deficiency Rickets Tetany
manifestation
Effect of excess Hypercalcemia Hypercalcemia Hypocalcemia 19
Roleof phosphorus:
Reciprocal relationship- ionic product in
serum- constant.
Normal adult- ca=10 mg/dl x p=4 mg/dl, so ionic
product= 40
High phosphorus may lead to low Ca - tetany
20
ROLE OF SERUM PROTEIN:
In hypoalbuminemia (eg. malnutrition)
total Ca is decreased.
About 0.8 mg/dL of calcium is reduced
with lowering of each g/dL of albumin
Metabolically active ionic form normal- no
deficiency manifestation
21
Acidosisand alkalosis:
Alkalosis favors binding of Ca with
protein low ionized Ca deficiency
manifested.
Renal threshold:
Renal threshold is 10 mg/dl. Excreted in
urine when level crosses 10 mg/dl.
22
CALCIUM RELATED
DISEASES
Hypercalcemia: plasma Ca > 11 mg/dl. Major
causes include
1. Hyperparathyroidism
2. Multiple myeloma
3. Paget’s disease
4. Metastatic carcinoma of bone
5. Thyrotoxicosis
6. Addison’s disease
23
HYPOCALCEMIA
Hypocalcemia: < 8.8 mg/dl
Causes include
Deficiency of Vitamin D
Deficiency of Parathyroid hormone
Increased Calcitonin
Intestinal malabsorption
Increase in Phosphorus level
24
PHOSPHORUS
Totalbody phosphate is about 1 kg;
80% of which is seen in bone and
teeth
25
INDICATIONS OF MEASURING SERUM
PHOSPHORUS LEVELS
1.Renal tubular disease
2. Hyperparathyroidism
3. Hypoparathyroidism
4. Bone diseases, such as rickets
5. Muscle weakness
6. Renal failure
26
REQUIREMENT AND SOURCE
Requirement is about 500 mg/day
Milkis a good source
Cereals, nuts and meat are moderate
sources
27
FUNCTIONS OF PHOSPHATE IONS
1. Formation of bone and teeth
2.Production of high energy phosphate.
compounds, such as ATP, CTP, GTP,
creatine phosphate, etc.
3.Synthesis of nucleoside co-enzymes, such
as NAD and NADP
4.DNA and RNA synthesis, where
phosphodiester linkages form the
backbone of the structure
28
5.Formation of phosphate esters, such as
glucose-6-phosphate, phospholipids
6.Formation of phosphoproteins, e.g. casein
7.Activation of enzymes by phosphorylation
8.Phosphate buffer system in blood. The
ratio of Na2HPO4: NaH2PO4 in blood is
4:1. This maintains the pH of blood at 7.4
29
SERUM LEVEL OF PHOSPHORUS
Serum level of phosphate is 3 – 4 mg/dL in
normal adults
Phosphorus holds an inverse relationship
with calcium.
An excess of serum calcium or phosphate
results in the excretion of the other by the
kidney.
The phosphate level is regulated by
excretion through urine.
Renal threshold is 2 mg/dL 30
Like calcium, phosphate level in
blood is controlled by the
parathyroid hormone.
PTH increases calcium and
phosphate release from the bone and
decreases loss of calcium and
increases loss of phosphate in the
urine
31
CAUSES OF HYPOPHOSPHATEMIA
Decreased absorption of phosphate
(Malabsorption)
Increased urinary excretion of phosphate
(Hyperparathyroidism)
Hypercalcemia
32
CAUSES OF HYPERPHOSPHATEMIA
Increased absorption of phosphate (Excess
vitamin D)
Increased cell lysis (Chemotherapy for
cancer)
Decreased excretion of phosphorus (Renal
impairment)
Hypocalcemia
33
QUESTIONS
Describe the sources, daily
requirement, absorption, functions of
calcium
Describe the mechanism of
regulation of blood calcium level
Name the causes of Hypocalcemia
Describe the functions of phosphorus
34