Calcium, Phosphorous, Magnesium

3 major forms of Ca in serum & %

50% ionized/free (iCa)

40% protein (albumin) bound

10% complexed w phosphate, citrate, bicarb, lactate

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most prevalent cation

99% skeleton

1% soft tissue

<0.2% extracellular fluid

bone

• osteoclast precursor

• osteoclast

• osteoblast

• osteoclast precursor → osteoclast → osteoblast

• osteoclast - bone resorption

• osteoblast - bone formation

homeostatic mechanism for ctrl of circulatory Ca levels

Ca maintained by

1. Ca absorption from intestines

2. kidney excretion

3. mvmt of Ca ions in/out of bone

hormones

1. parathyroid hormone

2. 1,25--dihydroxy vitamin D (active form of vit D = aka calcitriol)

Ca functions

1. bone formation

2. clotting cascade

3. muscle contraction/relax

4. nerve impulse transmission

5. enzyme activation

6. fat/carb metabolism

7. pH balance

A/L 5 causes for hypocalcemia

1. hypoalbuminemia (via chronic liver dz, nephrotic syndrome, CHF)

2. chronic renal dz

3. hyperphosphatemia

4. vit D defic

5. GI dz

6. alkalosis (m/c cause of low ionized Ca)

7. hypomagnesemia (→ impaired PTH secretion → PTH resistance)

8. (pseudo/)hypoparathyroidism

9. bone d/o - osteomalacia, Rickets, osteoporosis, Paget dz

when hypocalcemic → Ca inc via

• PTH

• vit D

PTH inc Ca

• gets Ca & PO4 from bone

• conserve Ca excretion by stim reabs by renal tubules

• inc rate of excretion of P in urine

• stim prodn of active vit D

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1,25-dihydroxy vit D

• inc intestinal absorption of dietary Ca ingested

• inc bone resorption

5 causes for hypercalcemia

1. hyperparathyroidism

2. cancer → tumor produce PTH-related proteins

3. hypervitaminosis D (inc skeletal resorption)

4. acromegaly (inc GH)

5. multiple myeloma (plasma proteins inc)

6. drug induced (thiazides, antacids w Ca)

7. chronic renal dz (inc renal retention, dec Ca excretion)

8. acidosis (inc ion Ca)

when hypercalcemia → Ca is dec

• PTH

1. xs Ca → turns off secretion of PTH by neg feedback

2. stim thyroid gland to secrete calcitonin (at high blood Ca) to inhibit activity of osteoclasts → suppress bone resorption

compare roles of what influences Ca levels

diet (medicine), presence of cancer, GI/bone/renal dz

differentiate at least 2 Ca methods used in the lab

1. atomic absorption

2. spectrophotometric method

3. ion selective electrode

spectrophotometric method for Ca

less accurate than AA

metallochromic indicator changes color when binds Ca, directly prop to [Ca]

• oCPC indicator - Mg & Fe can interfere → 8-hydroxyquinolone is used to minimize (580nm)

• Arsenazo III - higher Ca affinity (650nm)

ISE method for Ca

• fast, direct, easy to automate

• measures free Ca in plasma (Nerst eqn)

interferences

• anionic surfactants & ethanol

• falsely dec iCa

  • PO4, citrate, lactate, EDTA, EGTA, proteins, sulfate form complexes w Ca

  • higher pH → greater protein-bound → f-dec iCa

  • xs heparin → bind to free Ca → f-dec

how is Ca metabolism affected by parathyroid hormone (PTH)?

PTH inc Ca

• from bone

• reabs from kidney

• inc rate of P excreted in urine

• stim vit D

how is Ca metabolism affected by vitamin D?

inc dietary Ca absorption

hypoparathyroidism pathology

1. hyperexcitability : tetany or seizures

2. a rapid dec of Ca → assoc w hypotension & ECG abnromalities

hyperparathyroidism pathology

1. lethargy

2. vomiting

3. nausea

Ca sample req

serum, heparinized plasma

DON’T use EDTA → chelates Ca → inc K, dec Ca

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what are the methods to measure P?

special precautions?

spectrophotometric method

• P ion + ammonium molybdate → phosphomolybdate complex (340nm)

  • sensitive to L/I/H!

• or reduced → molybdenum blue (600-700nm), dependent on pH

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EDTA, citrate, oxalate interfere w formation of P-molybdate comlex!

incorporation of exogenous P

??

distribution of P in body

in almost all metabolism

55% free

35% complexed w Na, Ca, Mg

10% protein-bound

• organic P: mostly confined to soft tissues cells

• inorganic P: ECF (what is measured in lab)

role of P in regulation of various metabolic function

1. muscle, nervous system, rbc formation

2. generating & storing E for bone formation

3. constituent of nucleic acid, phospholipids, and phosphoproteins

4. intermediary metabolism of carb, prot, fats

fate of dietary P

??

hypophosphophatemia causes

1. intracellular shift

2. secondary hyperparathyroidism

3. renal tubuluar dz

4. malabsorption

5. intracellular depletion

6. tumor-induced osteomalacia

hyperphosphotemia causes

1. dec renal P excretion

2. hypoparathyroidism

3. acromegaly

4. inc PO4 intake

5. hypervit D

6. a shift of PO4 into ECF

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magnesium

• dietary sources

• distribution in body & forms

cofactors for 300 enzymes

diet: meat, green veg, spices, nuts

adult body

• 55% in bones

• 45% intracellular

• 1% extracellular

• 55% free

• 30% albumin bound

• 15% complexed w PO4, citrate

Mg functions

1. cell metabolism

2. nucleic acid synthesis

3. oxidative P’tion, replication, protein synthesis, enzyme activation

4. glycolysis

5. muscle contractions (opposite to Ca)

6. involved in N/K transport

hypomagnesemia causes

1. impaired GI absorption

   1. GI malabsorption d/o

   2. diarrhea

   3. xs vomiting

2. xs renal excretion or fluid loss

   1. chronic alcoholism/cirrhosis

   2. diuretics

   3. metabolic acidosis

   4. post kidney transplant

   5. diabetes mellitus

   6. pancreatitis?

hypermagnesemia

1. xs intake of Mg

   1. antacids w/ Mg hydroxide

   2. laxatives

2. renal failure - can’t excrete

effects on CNS of hypo vs hypermagnesemia

hypo

• hyperexcitability, twitching, muscle cramps, tetany, convulsions, irritability

hyper

• lethargy, dec respiration, CNS depression, muscle weakeness, BP drops might lead to cardiac arrest

• in pregnancy: to prevent preterm labor & protect baby from injury → inject high Mg (5 mg/dL expected while critical value 3-4 mg/dL, closely monitor every 3-6 hr)

spectrophotometric method for Mg

• most conventional method

• indicator calmagite+Mg complex (600nm)

• sensitive to hemolysis & lipemia

IS

ISE for Mg

not selective for Mg

iCa is measured & free Mg is calculated using signal from Mg electrode

Mg specimen req

serum, heparinized plasma

not acceptable: EDTA, citrate, and oxalate (will compete w Mg)

avoid hemolysis, intracellular leakage → f-high Mg

Ca // P // Mg ref ranges

Ca

serum total: 8.6 mg/dL

serum free: 4.6-5.3 mg/dL

urine 24h: 420-560 mg/day

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P

serum: 2.3-4.1 mg/dL

urine 24h: 0.4-1.3 g/day

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Mg

serum: 1.8-2.5 mg/dL

urine 24h: 6-10 mg/day