CALCIUM & PHOSPHORUS DR. AKIF AHSAN Assistant Professor

Dept. of Biochemistry JNMC, AMU, Aligarh

OBJECTIVES By the end of this session you should be able to:

Define principal elements & trace elements. 1.

Enumerate the functions of Ca & P. 2.

Tell the normal levels of Ca & P in blood. 3.

Discuss the factors affecting the absorption of Ca.

4.

Discuss the role of Vit-D, PTH & Calcitonin in Ca-P homeostasis.

5.

Minerals

Required in relatively large quantities (>100 mg/day) - Principal elements or macronutrients

Required in minute quantities (<100 mg/day) - Trace elements or micronutrients

Ca, P, Mg, Na, K, Cl and S

Fe, I, Cu, Zn, Co, Mn, Mo, Cr, Se and F

CALCIUM

Calcium

Most abundant mineral in human beings.

Total Ca: 1000 grams » 99% is present in bones and teeth (Calcium phosphate)

Different forms of CALCIUM

Hydroxyapatite Ca10(PO4)6(OH)2

in Plasma

45% - free ionized form

45% - bound to proteins

10% - complexed with anions (citrate, sulfate, phosphate)

Typically measured in routine blood tests (9-11 mg/dL).

Physiologically active

Functions of Ca

Formation of bones & teeth

Nerve conduction

Neuromuscular transmission

Excitation & contraction of muscles

Coagulation of blood

Action of hormones

Activation of enzymes

Actin filaments

Synaptic vesicles containing Neurotransmitter molecules

Synapsin-I Reserve Pool

Ca2+

Calmodulin dependent kinase II

ATP

ADP P

Releasable Pool

Neurotransmitter molecules are released by exocytosis

Coagulation of Blood

Some clotting factors (II, VII, IX, and X) require Ca2+(Factor IV): » For their enzymatic action. » To bind with phospholipids (of platelets and

tissues).

Many of the anticoagulants used to prevent in vitro coagulation of blood (Oxalate, citrate & EDTA), act by binding Ca ions.

Action of Hormones

Ionized Ca acts as a second messenger for some of the hormones (Angiotensin, GnRH, TRH, oxytocin).

Moreover, the secretion of hormones which are stored in granular form also requires the presence of Ca ions (Insulin, calcitonin, vasopressin).

Activation of Enzymes

via Calmodulin » activates kinases

Direct activation » pancreatic lipase » enzymes of coagulation pathway

PHOSPHORUS

Phosphorus

Total P: 700 grams » 80% in bones & teeth » Remainder is distributed all over the body (nerves & muscles are particularly rich in P)

Different forms of PHOSPHATE

Hydroxyapatite Ca10(PO4)6(OH)2 in Plasma

Intracellular Phosphate (Phospholipids, DNA, RNA,

ATP, ADP)

Circulating Phospholipids

Inorganic Phosphates (HPO4

2- & H2PO4-)

Physiologically active and is typically measured in routine blood

tests (2.5-4 mg/dL)

Formation of bones & teeth

Formation of high energy compounds

Role in metabolism

Formation of nucleic acids

Formation of membranes

Formation of nervous tissues

Maintenance of pH

Functions of P

Role in Metabolism

P is a constituent of many co-enzymes: » FMN » FAD » NAD » NADP » Thiamine pyrophosphate » Pyridoxal phosphate » Coenzyme A

MCQ

a) Phosphorus b) Sulfur c) Magnesium d) Iron

Which is a trace element?

[KEY: d]

MCQ

a) Calcium phosphate b) Free ionized calcium c) Calcium bound to albumin d) Calcium bound to citrate

Which form of calcium is physiologically active?

[KEY: b]

MCQ

a) Insulin b) Angiotensin c) GnRH d) Oxytocin

Ca2+ acts as a second messenger for all the following hormones, except:

[KEY: a]

MCQ

a) Cycline b) Calmodulin c) Collagen d) Kinesin

A small Ca binding protein that modifies the activity of many enzymes and other proteins in response to

changes of Ca2+ concentration, is known as:

[KEY: b]

ABSORPTION of Calcium

and Phosphorus

Absorption of Ca

Absorption of Ca occurs by an active uptake system in the upper part of small intestine. » 10-20% of the dietary Ca is absorbed.

Ca absorption is affected by: » pH » Calcium : Phosphorus ratio » Proteins » Vitamin-D & Paratharmone

Vit-D & PTH

Active form of Vit-D: Calcitriol » Vit-D is converted into its active form with the help of PTH.

Calcitriol acts on intestinal mucosa and induces the synthesis of: » Ca-binding protein (Calbindin) » Ca-dependent ATPase » Alkaline phosphatase

These are required for the active absorption of Ca.

Cholecalciferol Calcidiol

Calcitriol

Liver

Kidney Hydroxylase Hydroxylase

Ca-binding protein Ca-dependent ATPase Alklaline phosphatase

Calcium absorption

Int. mucosa

Int. mucosa

Plasma Ca

Parathyroid gland

PTH

Released into circulation

Induction

pH

A relatively low pH increases solubility of Ca salts. » This increases Ca absorption.

Proteins

Presence of proteins and amino-acids (lysine & arginine) in the food facilitates the absorption of Ca.

Calcium : Phosphorus Ratio

Oxalic acid, phytic acid and malabsorption syndrome decreases Ca absorption.

The ideal ratio is 1:1 but the absorption may occur satisfactorily as long as the ratio lies between 1:2 and 2:1.

Absorption of P

P is absorbed from the small intestine along with Ca.

If Ca absorption is normal, so will be that of P.

MCQ

a) Calcitriol b) Low pH c) Oxalates d) Amino acids

All of the following factors increase calcium absorption, except:

[KEY: c]

Calcium-Phosphate HOMEOSTASIS

Normal Levels & Requirements

CALCIUM

9-11 mg/dL

1000 mg

Normal plasma level

Daily requirement

PHOSPHORUS

2.5-4 mg/dL

700 mg

Normal plasma level

Daily requirement

Calcium-Phosphate Homeostasis

Body’s property to maintain the normal plasma level of Ca & P.

Ca-P homeostasis is mediated by: » Vit-D (calcitriol) » PTH » Calcitonin

Cholecalciferol (Vitamin D3)

Ergocalciferol (Vitamin D2)

7-Dehydrocholesterol Calcidiol Calcitriol

Vitamin D 25- Hydroxylase

Vitamin D 1α- Hydroxylase

PTH

↓ Serum Phosphate

FGF23

↑ Serum Phosphate

Vitamin-D activation

GI System

Calcium

Phosphate

Renal System

Bones

Endocrine System

Food

Feces

Absorption

Filtration Reabsorption

Urine

Bone Turnover

(Mediated by Hormones)

Calcium, Phosphate

Calcium, Phosphate

Calcium, Phosphate

Calcium, Phosphate

Calcitriol

Calcitriol

PTH PTH, Calcitriol

Calcitonin

Calcitonin

Calcium Phosphate

PTH

GI Tract

Kidneys

Bones FGF-23

Net Effect

Calcitriol: ↑ calcium, ↑ phosphate PTH: ↑ calcium, ↓ phosphate Calcitonin: ↓ calcium, ↓ phosphate

Ca-P homeostasis

Summary

Calcitriol Intestine Kidneys Bones

PTH Intestine Kidneys Bones

Calcitonin Intestine Kidneys Bones

↑ absorption of Ca & P

↑ reabsorption of Ca & P ↑ bone resorption

↑ Ca (& ↓ P ) reabsorption ↑ resorption & ↓ mineralization

↓ reabsorption of Ca & P ↓ bone resorption

↑ Calcium

↑ Phosphate

↑ Calcium

↓ Phosphate

↓ Calcium

↓ Phosphate

Acts via calcitriol

Hormone Organ Action Net Effect

MCQ

a) Calcitriol b) FGF23 c) Decreased serum phosphate d) Increased serum phosphate

Which of the following factors increases the activity of 1α- hydroxylase?

[KEY: c]

MCQ

a) Calcitriol b) PTH c) FGF23 d) Calcitonin

Urinary excretion of phosphate is increased by all, except:

[KEY: a]

MCQ

a) Both A and R are true and R is the correct explanation of A.

b) Both A and R are true but R is NOT the correct explanation of A.

c) A is true but R is false. d) A is false but R is true. e) Both A and R are false

Assertion: PTH decreases serum P levels. Reason: PTH enhances bone resorption.

[KEY: b]

CAN YOU ??? Define principal elements & trace elements. 1.

Enumerate the functions of Ca & P. 2.

Tell the normal levels of Ca & P in blood. 3.

Discuss the factors affecting the absorption of Ca.

4.

Discuss the role of Vit-D, PTH & Calcitonin in Ca-P homeostasis.

5.