7/31/2019 Ca Mg R

1/48

7/31/2019 Ca Mg R

2/48

Mineral content: average 70

kilogram man

Calcium 25.0mol 1 kg

Sodium 3.5 mol 30 g

Potassium 3.0 mol 120 g

Magnesium 1.0 mol 24 g

7/31/2019 Ca Mg R

3/48

Plasma calcium components

Calcium component % Total plasma calcium

Ionized calcium (Ca2+) 50-65

Protein bound calcium 30-45

Complexed calcium 5-10

7/31/2019 Ca Mg R

4/48

Plasma calcium components The physiologically active component is

plasma Ca2+

Ca2+ controls the feedback mechanismsresponsible for PTH secretion

7/31/2019 Ca Mg R

5/48

Calcium balance and requirementsBalance:

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

7/31/2019 Ca Mg R

6/48

Calcium requirements Late pregnancy and lactation: 2.0 g/day

recommended

Growing child: 1.0-1.5g/day

Human breast milk contains 300 mg/Lcalcium

7/31/2019 Ca Mg R

7/48

Phosphorus Normal daily intake in adults: 1.5-3.0 g

Minimum recommended intake: 1.0-1.5g/day

Defective absorption of calcium resultsin defective absorption of phosphorus

as a result of precipitation of calciumphosphate in the gut

7/31/2019 Ca Mg R

8/48

Phosphate absorption Enhanced by vitamin D probably secondary to

calcium

Reduced by giving aluminium hydroxide dueto precipitation of insoluble aluminiumphosphate

Plasma [phosphorus]: 0.8-1.4 mmol/L (from

inorganic phosphate) Organic phosphorus is mostly derived from

phospholipids and nucleic acids

7/31/2019 Ca Mg R

9/48

Plasma calcium and phosphate There is generally a reciprocal

relationship between the two in plasma

maintained through solution of bonesalt:

[Ca2+] x [phosphate] = 15 mg/dL

[Calc.] x [phosphate] = 35 mg/dL Metastatic calcification when product >

70 mg/dL

7/31/2019 Ca Mg R

10/48

Composition of bone 40% inorganic material

20% organic matrix

40% water

Ca2+

bone

ECF

7/31/2019 Ca Mg R

11/48

Bone formation Active osteoblasts synthesize and extrude

collagen

Collagen fibrils form arrays of an organicmatrix called the osteoid.

Calcium phosphate is deposited in theosteoid and becomes mineralized

Mineralization involves deposition of 3Ca3(P04)2 .Ca(OH)2 (hydroxyapatite).

7/31/2019 Ca Mg R

12/48

Bonescells

7/31/2019 Ca Mg R

13/48

Mineralization

Requires adequate Calcium andphosphate

Dependent on Vitamin D

Alkaline phosphatase and osteocalcinplay roles in bone formation

Their plasma levels are indicators ofosteoblast activity.

7/31/2019 Ca Mg R

14/48

Functions of calcium in the ECF Neuromuscular activity

Membrane permeability

Enzyme activity

Hormone action

Blood coagulaton

7/31/2019 Ca Mg R

15/48

7/31/2019 Ca Mg R

16/48

Parathyroid Hormonereference ranges

(

7/31/2019 Ca Mg R

17/48

Parathyroid hormone(0-1g/L)

Made up of 84 amino-acids

Pre-pro PTH contains 115 aa

25 + 6 aa removed from the N terminalend of pre-pro PTH PTH

Biological activity resides in N terminal30 aa

Principal fn is the control of ECF Ca2+

7/31/2019 Ca Mg R

18/48

PTH effect on the kidneys

Promotes the release of cAMP in the kidneys

Decreases the proximal tubular reabsorptionof phosphate

Reduces renal clearance of calcium

7/31/2019 Ca Mg R

19/48

Actions of parathyroidhormone

.

7/31/2019 Ca Mg R

20/48

Effect of PTH on glomerulus

.

7/31/2019 Ca Mg R

21/48

7/31/2019 Ca Mg R

22/48

Calcitonin and Katacalcinp CT:

7/31/2019 Ca Mg R

23/48

Formation of active vitamin D .

calcitriol

7/31/2019 Ca Mg R

24/48

Pathways of vitamin D metabolism

.

7/31/2019 Ca Mg R

25/48

Actions of vitamin D

Helps facilitated diffusion of calciumacross intestinal mucosal cells by

promoting synthesis of calcium bindingprotein in the intestines (1,25 / 24,25)

Promotes the release of calcium frombone by osteoclasts (1,25)

7/31/2019 Ca Mg R

26/48

Summary of metabolism of calcium

.

7/31/2019 Ca Mg R

27/48

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 changeswith the change in [albumin]

e.g. nephrotic syndrome

malnutrition, pregnancy, protein losingenteropathy

7/31/2019 Ca Mg R

28/48

H+ effect on plasma calcium

[H+] stronger binding of calcium toalbumin [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)

7/31/2019 Ca Mg R

29/48

In chronic renal failure

There is a decrease in plasma [calcium]

Rapid correction of acidosis rapid

[H+] stronger binding of ionizedcalcium tetany

7/31/2019 Ca Mg R

30/48

Metabolic bone disease1

Osteoporosis: Results of all routinechemical 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, butthe bone cannot maintain the same

mass of mineral matrix

7/31/2019 Ca Mg R

31/48

Metabolic bone disease2

Rickets and osteomalacia

Failure of deposition of calcium salts in

new bone

Increased amount of osteoid oruncalcified matrix

7/31/2019 Ca Mg R

32/48

Metabolic bone disease3Hyperparathyroidism

Primary

Parathyroid adenoma: (80-85% solitary

adenoma)

Parathyroid hyperplasia: (15-20%hyperplasia of all glands)

Parathyroid carcinoma: (

7/31/2019 Ca Mg R

33/48

HyperparathyroidismPresentation:.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

7/31/2019 Ca Mg R

34/48

Excessive resorption of bone

Proliferation of osteoclasts and

replacement of bone by fibrous tissue.

Bone cysts may form.

Hyperparathyroidism

Presentation:.2

7/31/2019 Ca Mg R

35/48

Hyperparathyroidism

Secondary

Malnutrition/ malabsorption syndrome

/vit D deficiency, 1-hydroxylasedeficiency, renal failure

plasma [Ca2+]

PTH

7/31/2019 Ca Mg R

36/48

Hyperparathyroidism

Tertiary

Malnutrition/ malabsorption syndrome

/vit D deficiency, 1-hydroxylasedeficiency/ renal failure plasma [Ca2+]

Hyperplasia/ adenoma of parathyroids PTHAutonomous PTH, / plasma [Ca2+]

7/31/2019 Ca Mg R

37/48

7/31/2019 Ca Mg R

38/48

7/31/2019 Ca Mg R

39/48

7/31/2019 Ca Mg R

40/48

Correction of plasma [calcium] usingthe plasma [albumin]

Formula:

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

[Calcium] in mmol/L

(Plasma albumin Ref: 35-50g/L)

7/31/2019 Ca Mg R

41/48

Investigations to consider inhypercalcaemia

Plasma [albumin]

Plasma fasting [phosphate]

Plasma [alkaline phosphatase] Plasma [urea] and [creatinine]

Plasma [PTH]

Plasma total [CO2] Urinary calcium excretion

Urinary hydroxyproline

7/31/2019 Ca Mg R

42/48

7/31/2019 Ca Mg R

43/48

Magnesium: absorption &excretion

Absorbed from both small and largeintestine

Only a small amount is present infaeces

Excretion is mainly urinary

7/31/2019 Ca Mg R

44/48

Magnesium: homeostasis

Plasma magnesium is normally keptwithin narrow limits 1.7-2.4 mg/100 ml

35% of the Mg in plasma is proteinbound

Factors concerned with Mg metabolismare not yet defined

Low [magnesium] tends to prevent PTHrelease and may cause hypocalcemia

[Magnesium] tends to follow that of Ca+

& K+

7/31/2019 Ca Mg R

45/48

7/31/2019 Ca Mg R

46/48

7/31/2019 Ca Mg R

47/48

Causes of Magnesium deficiencyplasmaMg 0.5 mmol/L

Abnormal losses

Renal disease: RTA & chronic

pyelonephritis

Extra-renal: diuretics, 1 & 2aldosteronism

Hyperparathyroidism

7/31/2019 Ca Mg R

48/48

Causes of Magnesium deficiencyplasmaMg 0.5 mmol/L

Reduced intake

Kwashiorkor

Marasmus