Ca++ Mg

1.

++

Metabolism

Synonyms: Blood Calcium, Ca, Total calcium Ionized calcium, Ca++ , Filterable calcium, Free calcium, Unbound calcium, Ionic calcium

2.

Mineral content: average 70 kilogram man

Calcium Sodium
Potassium Magnesium

25.0mol 3.5 mol

3.0 mol 1.0 mol

1 kg 30 g
120 g 24 g

Plasma calcium components

Calcium component Ionized calcium (Ca2+) Protein bound calcium Complexed calcium

% Total plasma calcium 50-65 30-45 5-10

Plasma calcium components

The physiologically active component is plasma Ca2+

Ca2+ controls the feedback mechanisms responsible for PTH secretion

Calcium balance and requirements

Balance: 0 in adults + in infancy and childhood in old age and in some disease states Requirements: Intake : 25 mmol (1g) / day Daily requirement : 0.5g / day

Calcium requirements

Late pregnancy and lactation: 2.0 g/day recommended Growing child: 1.0-1.5g/day Human breast milk contains 300 mg/L calcium

Phosphorus

Normal daily intake in adults: 1.5-3.0 g Minimum recommended intake: 1.0-1.5 g/day Defective absorption of calcium results in defective absorption of phosphorus as a result of precipitation of calcium phosphate in the gut

Phosphate absorption

Enhanced by vitamin D probably secondary to calcium Reduced by giving aluminium hydroxide due to precipitation of insoluble aluminium phosphate Plasma [phosphorus]: 0.8-1.4 mmol/L (from inorganic phosphate) Organic phosphorus is mostly derived from phospholipids and nucleic acids

Plasma calcium and phosphate

There is generally a reciprocal relationship between the two in plasma maintained through solution of bone salt: [Ca2+] x [phosphate] = 15 mg/dL [Calc.] x [phosphate] = 35 mg/dL Metastatic calcification when product > 70 mg/dL

Composition of bone

40% inorganic material 20% organic matrix 40% water Ca2+ bone ECF

Bone formation

Active osteoblasts synthesize and extrude collagen Collagen fibrils form arrays of an organic matrix called the osteoid. Calcium phosphate is deposited in the osteoid and becomes mineralized Mineralization involves deposition of 3Ca3 (P04)2 .Ca(OH)2 (hydroxyapatite).

Bones cells

Mineralization

Requires adequate Calcium and phosphate Dependent on Vitamin D Alkaline phosphatase and osteocalcin play roles in bone formation Their plasma levels are indicators of osteoblast activity.

Functions of calcium in the ECF

Neuromuscular activity Membrane permeability Enzyme activity Hormone action Blood coagulaton

Hormones involved with calcium metabolism

Plasma calcium elevating Parathyroid hormone 1,25Dihydroxycholecalciferol (calcitriol) Plasma calcium lowering Calcitonin Katacalcin

Parathyroid Hormone reference ranges

(<0.8-8.5pmol/L)

Parathyroid hormone (0-1g/L)

Made up of 84 amino-acids Pre-pro PTH contains 115 aa 25 + 6 aa removed from the N terminal end of pre-pro PTH PTH Biological activity resides in N terminal 30 aa Principal fn is the control of ECF Ca2+

PTH effect on the kidneys

Promotes the release of cAMP in the kidneys Decreases the proximal tubular reabsorption of phosphate Reduces renal clearance of calcium

Actions of parathyroid hormone

Effect of PTH on glomerulus

.thyroid gland structure

Calcitonin and Katacalcin p CT:<0.1 g/L

Produced by the C cells of the thyroid CT: 32 aa, KC: 21 aa Inhibit bone resorption Reduce hypercalcaemia towards normocalcaemia CT in pharmacological doses increases renal excretion of calcium and phosphate Marker for recurrence or metastasis of medullary carcinoma of the thyroid

Formation of active vitamin D .

calcitriol

Pathways of vitamin D metabolism

Actions of vitamin D

Helps facilitated diffusion of calcium across intestinal mucosal cells by promoting synthesis of calcium binding protein in the intestines (1,25 / 24,25) Promotes the release of calcium from bone by osteoclasts (1,25)

Summary of metabolism of calcium

Plasma calcium (2.12-2.62 mmol/L) Ca2+ (1.12-1.23 mmol/L)

PTH maintains the plasma Ca2+ constant Plasma albumin bound calcium changes with the change in [albumin] e.g. nephrotic syndrome malnutrition, pregnancy, protein losing enteropathy

H+ effect on plasma calcium

[H+] stronger binding of calcium to albumin [Ca2+] tetany A slow [H+] adjustment of [Ca2+] by PTH [H+] weaker binding of calcium to albumin (e.g. chronic renal failure, diabetic keto-acidosis, lactic acidosis)

In chronic renal failure

There is a decrease in plasma [calcium] Rapid correction of acidosis rapid [H+] stronger binding of ionized calcium tetany

Metabolic bone disease1

Osteoporosis: Results of all routine chemical tests are normal as a rule Urinary hydroxyproline There is loss of organic matrix and reduction in bone mass, seen on XR Deposition of calcium salts (mineralization) occurs normally, but the bone cannot maintain the same mass of mineral matrix

Metabolic bone disease2

Rickets and osteomalacia Failure of deposition of calcium salts in new bone Increased amount of osteoid or uncalcified matrix

Metabolic bone disease3 Hyperparathyroidism

Primary Parathyroid adenoma: (80-85% solitary adenoma) Parathyroid hyperplasia: (15-20% hyperplasia of all glands) Parathyroid carcinoma: (<0.5%)

Hyperparathyroidism Presentation:.1

Often asymptomatic Polyuria, polydipsia,weakness, tiredness Abdominal pain, pancreatitis Associated with MEN and ZE Associated with PUs, duodenal: gastric = 7:1 plasma [Ca2+] , PTH, PO43-* Renal calculi and nephrocalcinosis Metabolic bone disease

Hyperparathyroidism Presentation:.2

Excessive resorption of bone Proliferation of osteoclasts and replacement of bone by fibrous tissue. Bone cysts may form.

Hyperparathyroidism
Secondary Malnutrition/ malabsorption syndrome /vit D deficiency, 1-hydroxylase deficiency, renal failure plasma [Ca2+] PTH

Hyperparathyroidism
Tertiary Malnutrition/ malabsorption syndrome /vit D deficiency, 1-hydroxylase deficiency/ renal failure plasma [Ca2+] Hyperplasia/ adenoma of parathyroids PTH Autonomous PTH, / plasma [Ca2+]

Causes of hypercalcaemia

Artefact: Excessive venous stasis Parathyroid disease 1(MEN) and 3 Ectopic PTH production Bone disease: Cancer with osteolytic deposits, multiple myeloma, leukaemia, Pagets , Sarcoidosis Vitamin D intoxication Familial hypocalciuric hypercalcaemia

Causes of hypocalcaemia

Thyroid or parathyroid surgery If PO3-4 , chronic renal failure, hypoparathyroidism, pseudohypoparathyroidism, acute rhabdomyolysis (plasma [Ca2+] , PO43-, K+ ) If PO3-4 or , osteomalacia (ALP), overhydration or pancreatitis
(Fat necrosis lipolysis saponification sequestration of Ca2+)

Causes of hypocalcaemia

Respiratory alkalosis: total calcium may be normal whereas Ca2+ may be depressed.

Correction of plasma [calcium] using the plasma [albumin]

Formula: (40-[albumin] x 0.02) + [calcium]

[Calcium] in mmol/L (Plasma albumin Ref: 35-50g/L)

Investigations to consider in hypercalcaemia

Plasma [albumin] Plasma fasting [phosphate] Plasma [alkaline phosphatase] Plasma [urea] and [creatinine] Plasma [PTH] Plasma total [CO2] Urinary calcium excretion Urinary hydroxyproline

Magnesium
Second most abundant ICF cation Only a small fraction in the ECF 65% of the bodys magnesium in bone, 35% in cells Requirements Daily intake 10 mmol (250 mg) Significant quantities in gastric and biliary secretions

Magnesium: absorption & excretion

Absorbed from both small and large intestine Only a small amount is present in faeces Excretion is mainly urinary

Magnesium: homeostasis

Plasma magnesium is normally kept within narrow limits 1.7-2.4 mg/100 ml 35% of the Mg in plasma is protein bound Factors concerned with Mg metabolism are not yet defined Low [magnesium] tends to prevent PTH release and may cause hypocalcemia [Magnesium] tends to follow that of Ca+ &K+

Magnesium: homeostasis

There are specific Mg malabsorption syndromes Renal conservation mechanisms are very efficient Mg deficiency paraesthesia, fits, tetany, muscle weakness, cardiac arrhythmias Usually there is also K+ & Ca2+

Causes of Magnesium deficiency plasma Mg 0.5 mmol/L

Abnormal losses Prolonged GIT aspiration Diarrhoea Malabsorptive disease Alcohol Fistula Keto-acidosis Small bowel resection

Causes of Magnesium deficiency plasma Mg 0.5 mmol/L

Abnormal losses Renal disease: RTA & chronic pyelonephritis Extra-renal: diuretics, 1 & 2 aldosteronism Hyperparathyroidism

Causes of Magnesium deficiency plasma Mg 0.5 mmol/L

Reduced intake Kwashiorkor Marasmus