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Chemical Pathology > Calcium And Magnesium Metabolism > Flashcards

Calcium And Magnesium Metabolism Flashcards

1
Q

State one function of calcium

A

Ca2+ controls the feedback mechanisms responsible for PTH secretion

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2
Q

Which people need calcium

A

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

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3
Q

What are the calcium balance and requirements

A

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

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4
Q

What is the most important anion associated with calcium

A

Phosphate

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5
Q

What is the normal daily intake of phosphate

A

1.5-3 g

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6
Q

What is the normal recommended intake of phosphate

A

1 - 1.5g/day

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7
Q

Defective absorption of calcium results in defective absorption of ……. as a result of ……

A

Phosphorus, precipitation of calcium phosphate in the gut

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8
Q

Describe phosphate absorption

A

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

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9
Q

What is the composition of bone

A

40% inorganic material
●20% organic matrix
●40% water
●There is a dynamic relationship between bone and ECF calcium:
Ca2+
bone ⇔ ECF

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10
Q

Describe plasma calcium and phosphate absorption

A

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

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11
Q

Describe mineralization of bone

A

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.

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12
Q

What are some functions of calcium in the ECF

A

Mineralization of bone
●Neuromuscular activity (e.g. generation of nerve impulse / cardiac muscle contraction)
●Membrane permeability
●Intracellular signalling
●Enzyme activity
●Hormone action
●Blood coagulaton

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13
Q

What are some hormones involved with calcium metabolism

A

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

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14
Q

What is parathyroid hormone

A

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

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15
Q

What is PTH-RP

A

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

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16
Q

What is the effect of PTH on the kidneys

A

Promotes the release of cAMP in the kidneys
●Decreases the proximal tubular reabsorption of phosphate (causes phosphaturia)
●Reduces renal clearance of calcium

17
Q

What is calcitonin and katacalcin

A

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

18
Q

What are some actions of vitamin D

A

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)

19
Q

What is plasma calcium

A

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

20
Q

What is H+ effect on plasma calcium

A

●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

21
Q

With respect to calcium, what occurs in renal failure

A

Reduction in protein bound calcium
●A decrease in plasma total calcium
●Rapid correction of acidosis rapid [H+]  stronger binding of ionized calcium tetany

22
Q

With respect to calcium, what happens in osteoporosis

A

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

23
Q

With respect to calcium, what happens to rickets and osteomalacia

A

Failure of deposition of calcium salts in new bone
●Increased amount of osteoid or uncalcified matrix

24
Q

What is hyperparathyroidisn

A

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+]

25
Q

What are some causes of hypercalcemia

A

Artefact: Excessive venous stasis
●Parathyroid disease 1(MEN) and 3
●Ectopic PTH production
●Bone disease: Cancer with osteolytic deposits, multiple myeloma, leukaemia, Paget’s (usually normocalc) , Sarcoidosis: (10-20%)
●Vitamin D intoxication
●Familial hypocalciuric hypercalcaemia

26
Q

What are some causes of hypocalcemia

A

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+)

27
Q

What is the formula to correct plasma calcium with plasma (albumin)

A

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

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

28
Q

What are some investigations to consider in hypercalcemia

A

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

29
Q

What is magnesium

A

Second most abundant ICF cation
●Only a small fraction in the ECF
●65% of the body’s magnesium in bone, 34% in cells and 1% extra-cellular

30
Q

What is the daily intake of magnesium

A

Daily intake 10 mmol (250 mg)
●Significant quantities in gastric and biliary secretions

31
Q

Describe the absorption and excretion of magnesium

A

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

32
Q

Describe the homeostasis of magnesium

A

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 Ca2+ & K +
●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+

33
Q

Magnesium deficiency is plasma magnesium below …….

A

0.5 mmol/L

Chemical Pathology (16 decks)

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