Magnesium, Calcium, Phosphate, Lactate

• Magnesium


  Mg+2 (divalent cation), second major intracellular cation after potassium, important for neuromuscular conduction, enzyme phosphorylation, and protein anabolism
• Distribution of Magnesium in the body

  • Bone 53%, Muscle and other organs 46%, Serum and RBC less than 1%
• Forms of Magnesium in Serum (Blood)


  • Protein Bound (Albumin) 33%, Free/Ionized Form 61%, Complexed with Phosphate and Citrate 5%
• Hormones that regulate Magnesium

  Parathyroid hormone (PTH) promotes renal reabsorption and intestinal absorption of magnesium, Aldosterone and Thyroxine increase renal excretion of Mg and K; Na reabsorption
• Clinical Applications of Magnesium

  • Cause of HYPOmagnesemia: Reduced intake, decreased absorption, others
• Causes of HYPOmagnesemia


  • Reduced intake of food rich in Mg (poor diet/starvation, prolonged Mg deficiency, chronic alcoholism), Decreased absorption (malabsorption syndrome, pancreatitis, diarrhea, vomiting, laxative, neonatal due to surgery, primary selective malabsorption, congenital transport defect in SI ), Others (excess lactation, pregnancy)
• Causes of HYPOmagnesemia - Increased Excretion

  • Renal (tubular disorder, pyelonephritis, glomerulonephritis), Drug Induced (diuretics, antibiotics, cyclosporin, digitalis and digoxin), Endocrine (hyperparathyroidism, hyperaldosteronism, hyperthyroidism, hypercalcemia, diabetic ketoacidosis)
• Causes of HYPERmagnesemia


  • Decreased excretion (acute/chronic renal failure, hypoaldosteronism), Increased intake (medications and therapy, antacids, dehydration), Pseudo Hypermagnesemia, Bone Carcinoma and Bone metastases
• Determination of Magnesium


  Specimen: Serum/Plasma (lithium heparin, 24 hr urine), Hemolysis cause: False increase, Methods: mostly colorimetric
• MgCl2 is basic
• Determination of Magnesium


  1. Specimen: Serum/ Plasma (lithium heparin, 24 hr urine)

  2. Hemolysis cause: False increase

  3. Methods: Calmagite, Formazan Dye, Methylthymol blue, Titan Yellow, Fluorometric
• Calmagite Method


  1. Measurement of absorbance at 532 nm

  2. Reaction: Mg + Calamite—> Reddish violet (532nm)
• Formazan Dye Method


  1. Measurement of colored complex at 660nm

  2. Reaction: Mg + Dye—> Colored complex (660nm)
• Methylthymol blue Method


  1. Measurement of the absorbance

  2. Reaction: Mg + chromogen—> blue colored complex
• Titan Yellow


  Reaction: Serum TCA filtrate + Titan Yellow—> red compound
• Trichloro-acetic Acid (TCA) is used as a deproteinizing agent
• Fluorometric method


  Reaction: Mg + 8-hydroxy-5-quinoline sulfonic acid—> Fluorescence (380-410nm)
• Reference Values for Magnesium

  • 0.63 - 1.0 mmol/L
  • 1.26 - 2.10 mEq/L
• Calcium


  • A divalent cation (Ca+2)
  • Used for muscle contraction
  • Evaluated with phosphorus for bone metabolism
  • Used for blood coagulation
• Calcium is important in blood coagulation activation


  Calcium is Factor IV
• Calcium is absorbed in the small intestine in the presence of vitamin D


  • Vitamin D is essential for the intestinal absorption of calcium
  • Vitamin D will not be absorbed if it is in “inactivated” form
• Distribution of Calcium in the Blood

  • Ionized Ca+2
  • Protein-bound Ca+2
  • Complex Ca+2
• Factors affecting Ca+2 level in blood: bone resorption/destruction, bone deposition/mineralization, intestinal absorption
• Bone resorption/ Bone destruction

  • Promoted by Osteoclast cells
  • Causes calcium elevation in the blood
  • Promoted by action of hormone PTH
• Bone Deposition/ Bone mineralization

  • Promoted by osteoblast cells
  • Promoted by action of hormone calcitonin
  • Use: Can cause decrease calcium level in the plasma
  • Bone deposition happens when calcium in the plasma is too much
• Calcium regulation in the body

  Activated when there is hypercalcemia

  Bone deposition happens when calcium in the plasma is too much and will be transported to the bones. If there is a deficiency of calcium in the plasma, the bones will release calcium. Calcium is not excreted, it is either in the plasma or bones

  
  

  while...

  Bone resorption activates when there is hypocalcemia

  Bone deposition activates when there is hypercalcemia
• Intestinal Absorption of Calcium


  Calcium is absorbed in the small intestine in the presence of activated Vitamin D. Vitamin D can be obtained from the diet (inactive) and exposure to sunlight helps to activate it. Without Vitamin D, calcium absorption is not possible
• Melanin provides protection from harmful sun rays, preventing skin diseases or cancer. Excessive melanin can block UV exposure, leading to certain disorders. African Americans have high melanin and are prone to bone diseases like osteomalacia and Rickets due to calcium deficiency
• Bone disease is common among African Americans due to excessive melanin blocking UV rays exposure, preventing Vitamin D activation and leading to calcium deficiency
• Activation of Parathyroid Gland (PTG)

  Activated when calcium is low in the plasma and suppressed when calcium is high. In hypercalcemia, PTG is suppressed as there is no need for calcium release from bones. In hypocalcemia, PTG is activated to promote calcium reabsorption and activation of renal 1-a-hydroxylase
• 1. a-hydroxylase promotes the hydroxylation of substrate to activate circulating vitamin D, converting it to the physiologically active form 1-25 dihydroxy vitamin D
• 1-25 dihydroxy vitamin D is the physiologically active form of vitamin D, specifically for calcium reabsorption. Vitamin D3 or cholecalciferol is the specific active form
• Hydroxylation of the substrate occurs in the liver and kidneys to activate vitamin D3 or cholecalciferol
• Stimulation of osteoclastic activity by PTH in bones

  PTH stimulates osteoclastic activity, releasing Ca++ and HPO
• Vitamin D3


  Specific vitamin D active for calcium reabsorption
• Organs where hydroxylation of the substrate occurs

  • Liver
  • Kidneys
• In Bone, PTH stimulates osteoclastic activity


  Releases Ca++ and HPO4-
• In the kidney, PTH promotes

  1. Absorption of Ca++

  2. Excretion of HPO4-

  3. Activation of renal 1-a-hydroxylase
• Vitamin D promotes


  1. Intestinal absorption of Ca++ and HPO4-

  2. Renal reabsorption of Ca++ and HPO4-
• Cause of Hypocalcemia ( ↓ Ca+)


  1. Primary hypoparathyroidism

  2. Hypo/hypermagnesemia

  3. Hypoalbuminemia

  4. Acute Pancreatitis

  5. Vit. D deficiency

  6. Renal Disease

  7. Rhabdomyolysis