Calcium And Magnesium Metabolism Flashcards
State one function of calcium
Ca2+ controls the feedback mechanisms responsible for PTH secretion
Which people need calcium
Late pregnancy and lactation: 2.0 g/day recommended
●Growing child: 1.0-1.5g/day
●Human breast milk contains 300 mg/L calcium
●Large amounts of phosphates and fatty acids complex with calcium and prevent absorption
What are the calcium balance and requirements
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
●Absorption : 0.25-0.5g / day
What is the most important anion associated with calcium
Phosphate
What is the normal daily intake of phosphate
1.5-3 g
What is the normal recommended intake of phosphate
1 - 1.5g/day
Defective absorption of calcium results in defective absorption of ……. as a result of ……
Phosphorus, precipitation of calcium phosphate in the gut
Describe 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
What is the composition of bone
40% inorganic material
●20% organic matrix
●40% water
●There is a dynamic relationship between bone and ECF calcium:
Ca2+
bone ⇔ ECF
Describe plasma calcium and phosphate absorption
Absorption produces a direct relationship between the two. PTH regulation produces a reciprocal relationship between the two
●[Ca2+] x [phosphate] = 15 mg/dL
●[Calc.] x [phosphate] = 35 mg/dL
●Metastatic calcification starts when product > 70 mg/dL
Describe mineralization of bone
Requires adequate calcium and phosphate
●Dependent on Vitamin D
●Alkaline phosphatase and osteocalcin play roles in bone formation
●Their plasma levels are indicators of osteoblastic activity.
What are some functions of calcium in the ECF
Mineralization of bone
●Neuromuscular activity (e.g. generation of nerve impulse / cardiac muscle contraction)
●Membrane permeability
●Intracellular signalling
●Enzyme activity
●Hormone action
●Blood coagulaton
What are some hormones involved with calcium metabolism
Plasma calcium elevating:
●Parathyroid hormone
●1,25–Dihydroxycholecalciferol (calcitriol)
Plasma calcium lowering:
●Calcitonin
●Katacalcin
What is parathyroid hormone
84 aa
●Synthesised by parathyroid glands
●Bio-activity in aa 1-34 (N-terminal fragment)
●Intact PTH T1/2 is 3-4 mins
●Synthesis inhibited by 1,25 vit D
●Secretion inhibited by hypercalcaemia
25 + 6 aa removed from the N terminal end of pre-pro PTH⇒ PTH
●Biological activity resides in N terminal 30-34 aa
●Principal fn is the control of ECF Ca2+
●Metabolized by renal, hepatic and bone cells
What is PTH-RP
Peptide hormone with similar aa sequence at the N terminal as PTH
●Activates same receptors as PTH
●Function uncertain, may be important in calcium metabolism in the fetus
●Gene for PTH-RP widely distributed in the tissues but normally suppressed
●May cause hypercalcaemia in some tumours in which it is derepressed
What is the effect of PTH on the kidneys
Promotes the release of cAMP in the kidneys
●Decreases the proximal tubular reabsorption of phosphate (causes phosphaturia)
●Reduces renal clearance of calcium
What is calcitonin and katacalcin
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
What are some 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)
What is plasma calcium
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
What is H+ effect on plasma calcium
●rapid [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. in: chronic renal failure, diabetic keto-acidosis, lactic acidosis)
Key: = increase, = decrease, = leads to
With respect to calcium, what occurs in renal failure
Reduction in protein bound calcium
●A decrease in plasma total calcium
●Rapid correction of acidosis rapid [H+] stronger binding of ionized calcium tetany
With respect to calcium, what happens in osteoporosis
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
With respect to calcium, what happens to rickets and osteomalacia
Failure of deposition of calcium salts in new bone
●Increased amount of osteoid or uncalcified matrix
What is hyperparathyroidisn
Primary
●Parathyroid adenoma: (80-85% solitary adenoma)
●Parathyroid hyperplasia: (15-20% hyperplasia of all glands)
●Parathyroid carcinoma: (<0.5%)
Often asymptomatic
●Polyuria, polydipsia,weakness, tiredness
●Abdominal pain, pancreatitis
●Associated with MEN and ZE
●Associated with PUs, duodenal: gastric = 7:1
●Plasma Chem: plasma [Ca2+] , [PTH], [PO43-]
●Renal calculi and nephrocalcinosis
●Metabolic bone disease
Excessive resorption of bone
●Proliferation of osteoclasts and replacement of bone by fibrous tissue.
●Bone cysts may form.
Secondary
●Malnutrition/ malabsorption syndrome /vit D deficiency, 1-hydroxylase deficiency, renal failure (any of the above resulting in):
●plasma [Ca2+]
● PTH
Tertiary
●History of: 2˚ hyperparathyroidism
●(Malnutrition/ malabsorption syndrome /vit D deficiency, 1-hydroxylase deficiency/ renal failure
plasma [Ca2+] leading to):
●Hyperplasia/ adenoma of parathyroids
● PTH
●Autonomous PTH, / plasma [Ca2+]
