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PRESENTED BY
SHREYA JHA
 The total body stores of magnesium are
between 21 and 28 g in the average 70 kg
adult.
 Normal serum magnesium usually ...
 Magnesium is the second-most abundant
intracellular cation and, overall, the fourth-most
abundant cation.
 Intracellula...
In plasma
• 60% of Mg exists as physiologically active
ionised form
• 30% is protein bound mainly to albumin
• remaining 1...
 About 30-40% of dietary magnesium (140–
360 mg/d) is absorbed, principally in the
jejunum and ileum.
 Absorption is sti...
 Serum magnesium concentration is regulated by
renal magnesium reabsorption.
 Parathyroid hormone increases magnesium
re...
About 60% of magnesium is reabsorbed in
the cortical thick ascending limb of loop of
Henle (cTAL), whereas 20% of filtered...
THICK ASCENDING LIMB OF LOOP OF HENLE
• Paracellular Mg transport is driven by a favorable
lumen positive electrochemical ...
DISTAL CONVOLUTED TUBULE
• The transport rate in this segment defines the
final urinary Mg+ concentration as no
reabsorpti...
 Hypomagnesemia is an electrolyte
disturbance in which there is an abnormally
low level of magnesium in the blood.
 Hypo...
I. Related to decreased Mg intake
 Starvation
 Alcohol dependence
 Total parenteral nutrition
II. Related to redistribu...
III. Related to GI Mg loss
 Diarrhea
 Vomiting and nasogastric suction
 Gastrointestinal fistulas and ostomies
 Hypoma...
IV. Related to renal Mg loss
 Gitelman syndrome
 Classic Bartter syndrome (Type III Bartter
syndrome)
 Familial hypomag...
DRUGS
 Diuretics - Loop diuretics, osmotic diuretics,
and chronic use of thiazides
 Antimicrobials - Amphotericin B,
ami...
OTHERS
 Hypercalcemia
 Chronic metabolic acidosis
 Volume expansion
 Primary hyperaldosteronism
 Recovery phase of ac...
 Alcoholics and individuals on magnesium-
deficient diets or on parenteral nutrition for
prolonged periods can become
hyp...
 Hungry bone syndrome, in which magnesium is
removed from the extracellular fluid space and
deposited in bone following p...
 Hyperadrenergic states, such as alcohol
withdrawal, may cause intracellular shifting of
magnesium and may increase circu...
 When the small bowel is involved, due to
disorders associated with malabsorption,
chronic diarrhea, or steatorrhea, or a...
 Hypomagnesemia with secondary hypocalcemia (HSH) is a
rare autosomal-recessive disorder characterized by
profound hypoma...
 Familial hypomagnesaemia with hypercalciuria
and nephrocalcinosis (FHHNC), an autosomal-
recessive disorder, there is pr...
 Autosomal-dominant hypocalcemia with
hypercalciuria (ADHH) is another disorder of
urinary magnesium wasting.
 Individua...
 Isolated dominant hypomagnesemia (IDH) with
hypocalciuria is an autosomal-dominant condition
associated with few symptom...
Bartter’s syndrome
 Autosomal recessive disorder involving
impaired Thick Ascending Limb salt
reabsorption
Gitelman syndr...
 Drugs like loop diuretics (including
furosemide, bumetanide, and ethacrynic
acid), produce large increases in magnesium
...
 Aminoglycosides are thought to induce the action
of the CaSR on the TAL and DCT, producing
magnesium wasting
 Cisplatin...
The risk of hypomagnesemia can be
summarized as follows:
 2% in the general population
 10-20% in hospitalized patients
...
 A careful family history is important,
particularly when acquired causes of
hypomagnesemia have to be excluded
 Often a...
 Hypokalemia is a common event in patients with
hypomagnesemia, occurring in 40-60% of cases
 Partly due to underlying d...
 The classic sign of severe hypomagnesemia (<
1.2 mg/dL) is hypocalcemia.
 The mechanism is multifactorial.
 Impaired m...
 The cardiovascular effects of magnesium deficiency
include effects on electrical activity, myocardial
contractility, pot...
 Hypertension is seen in cases of
hypomagnesemia due to decrease in
intracellular free magnesium that causes an
increase ...
 The earliest manifestations of magnesium
deficiency are usually neuromuscular and
neuropsychiatric disturbances, the mos...
 Measurement of serum magnesium
 Its use in evaluating total body stores is
limited
Mg++ Normal
sMg 1.7 – 2.5 mg/dl
RBC ...
 Because 30% of magnesium is bound to
albumin and is therefore inactive,
hypoalbuminemic states may lead to
spuriously lo...
GOLD STANDARD
 A surrogate for direct intracellular magnesium is
the measurement of magnesium retention after
acute magne...
Excretion Analysis
FEMg = [(UMg x PCr) / (PMg x UCr x 0.7)]
 distinction between gastrointestinal and renal
losses can be...
Diet
 The normal recommended daily allowance of Mg
is 420 mg for men and 320 mg for women
 Green vegetables such as spin...
 oral replacement should be given in the
asymptomatic patient, preferably with a
sustained-release preparation
 Bioavail...
 The hypocalcemic-hypomagnesemic patient with
tetany or the patient who is suspected of having
hypomagnesemic-hypokalemic...
 The main adverse effect of Mg replacement is
hypermagnesemia due to administration at an
excessive rate or excessive amo...
 Patients with diuretic-induced hypomagnesemia who
cannot discontinue diuretic therapy may benefit from
the addition of a...
 Brenner and Rector’s THE KIDNEY 9th edition
 Harrison’s principles of internal medicine,
17th edition
 Medscape.com
THANK YOU!!!!
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Hypomagnesemia

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Hypomagnesemia

  1. 1. PRESENTED BY SHREYA JHA
  2. 2.  The total body stores of magnesium are between 21 and 28 g in the average 70 kg adult.  Normal serum magnesium usually has a range of 1.7 to 2.5 mg/dL.  Most of the body's magnesium is in the skeletal bone mass, which accounts for more than 50% of the body's stores.  The remainder is located in soft tissue, of which only 1% is located extracellularly.
  3. 3.  Magnesium is the second-most abundant intracellular cation and, overall, the fourth-most abundant cation.  Intracellular magnesium is an important cofactor for various enzymes, transporters, and nucleic acids that are essential for normal cellular function, replication, and energy metabolism
  4. 4. In plasma • 60% of Mg exists as physiologically active ionised form • 30% is protein bound mainly to albumin • remaining 10 % forms complexes with plasma anions such as phosphates and citrates
  5. 5.  About 30-40% of dietary magnesium (140– 360 mg/d) is absorbed, principally in the jejunum and ileum.  Absorption is stimulated by 1,25(OH)2 D.  Magnesium excretion in urine usually matches net intestinal absorption (100 mg/d).
  6. 6.  Serum magnesium concentration is regulated by renal magnesium reabsorption.  Parathyroid hormone increases magnesium reabsorption in the cTAL, whereas hypercalcemia and hypermagnesemia inhibit magnesium reabsorption.
  7. 7. About 60% of magnesium is reabsorbed in the cortical thick ascending limb of loop of Henle (cTAL), whereas 20% of filtered magnesium is reabsorbed in the proximal tubule, and another 5–10% in the distal convoluted tubule. PROXIMAL TUBULE • Mg absorption in the proximal tubule is dependant on the filtered load as well as net salt and water reabsorption.
  8. 8. THICK ASCENDING LIMB OF LOOP OF HENLE • Paracellular Mg transport is driven by a favorable lumen positive electrochemical gradient which is generated by a transcellular reabsorption of NaCl • It is dependant on the activity of Na+-k+-cl- cotransporter, renal outer medullary channel, Na+-k+-ATPase pump and renal Cl- channel • Claudins are the major components of tight- junction strands in the TAL, where the reabsorption of magnesium occurs
  9. 9. DISTAL CONVOLUTED TUBULE • The transport rate in this segment defines the final urinary Mg+ concentration as no reabsorption takes place beyond this level • The cells in this nephron segment have highest energy consumption of the nephrons • Na+-cl- cotransporter, which is exclusively present in the DCT is important for active reabsorption of Mg  Approx 3% of filtered Mg is excreted in the urine
  10. 10.  Hypomagnesemia is an electrolyte disturbance in which there is an abnormally low level of magnesium in the blood.  Hypomagnesemia is not necessarily magnesium deficiency. Hypomagnesemia can be present without magnesium deficiency and vice versa.
  11. 11. I. Related to decreased Mg intake  Starvation  Alcohol dependence  Total parenteral nutrition II. Related to redistribution of Mg from ECF to ICF  Hungry bone syndrome  Treatment of diabetic ketoacidosis  Alcohol withdrawal syndromes  Refeeding syndrome  Acute pancreatitis
  12. 12. III. Related to GI Mg loss  Diarrhea  Vomiting and nasogastric suction  Gastrointestinal fistulas and ostomies  Hypomagnesemia with secondary hypocalcemia (HSH)
  13. 13. IV. Related to renal Mg loss  Gitelman syndrome  Classic Bartter syndrome (Type III Bartter syndrome)  Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC)  Autosomal-dominant hypocalcemia with hypercalciuria (ADHH)  Isolated dominant hypomagnesemia (IDH) with hypocalciuria  Isolated recessive hypomagnesemia (IRH) with normocalcemia
  14. 14. DRUGS  Diuretics - Loop diuretics, osmotic diuretics, and chronic use of thiazides  Antimicrobials - Amphotericin B, aminoglycosides, pentamidine, capreomycin, viomycin, and foscarnet  Chemotherapeutic agents - Cisplatin  Immunosuppressants - Tacrolimus and cyclosporine  Proton-pump inhibitors  Ethanol
  15. 15. OTHERS  Hypercalcemia  Chronic metabolic acidosis  Volume expansion  Primary hyperaldosteronism  Recovery phase of acute tubular necrosis  Postobstructive diuresis
  16. 16.  Alcoholics and individuals on magnesium- deficient diets or on parenteral nutrition for prolonged periods can become hypomagnesemic without abnormal gastrointestinal or kidney function.  The addition of 4-12 mmol of magnesium per day to total parenteral nutrition has been recommended to prevent hypomagnesemia.
  17. 17.  Hungry bone syndrome, in which magnesium is removed from the extracellular fluid space and deposited in bone following parathyroidectomy or total thyroidectomy or any similar states of massive mineralization of the bones  Hypomagnesemia may also occur following insulin therapy for diabetic ketoacidosis and may be related to the anabolic effects of insulin driving magnesium, along with potassium and phosphorus, back into cells.
  18. 18.  Hyperadrenergic states, such as alcohol withdrawal, may cause intracellular shifting of magnesium and may increase circulating levels of free fatty acids that combine with free plasma magnesium.  Refeeding syndrome is a condition in which previously malnourished patients are fed high carbohydrate loads, resulting in a rapid fall in phosphate, magnesium, and potassium, along with an expanding extracellular fluid space volume, leading to a variety of complications.
  19. 19.  When the small bowel is involved, due to disorders associated with malabsorption, chronic diarrhea, or steatorrhea, or as a result of bypass surgery on the small intestine.  Patients with ileostomies can develop hypomagnesemia as there is some degree of magnesium absorption in the colon
  20. 20.  Hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal-recessive disorder characterized by profound hypomagnesemia associated with hypocalcemia.  Pathophysiology is related to impaired intestinal absorption of magnesium accompanied by renal magnesium wasting as a result of a reabsorption defect in the DCT.  Mutations in the gene coding for TRPM6, a member of the transient receptor potential (TRP) family of cation channels, have been identified as the underlying genetic defect.  Patients usually present within the first 3 months of life with the neurologic symptoms of hypomagnesemic hypocalcemia, including seizures, tetany, and muscle spasms.
  21. 21.  Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC), an autosomal- recessive disorder, there is profound renal magnesium and calcium wasting.  The hypercalciuria often leads to nephrocalcinosis, resulting in progressive renal failure.  Other symptoms reported in patients with FHHNC include urinary tract infections, nephrolithiasis, incomplete distal tubular acidosis, and ocular abnormalities
  22. 22.  Autosomal-dominant hypocalcemia with hypercalciuria (ADHH) is another disorder of urinary magnesium wasting.  Individuals who are affected present with hypocalcemia, hypercalciuria, and polyuria  About 50% of these patients have hypomagnesemia  ADHH is produced by mutation of CaSR gene (calcium-sensing receptor) which is involved in renal calcium and magnesium reabsorption
  23. 23.  Isolated dominant hypomagnesemia (IDH) with hypocalciuria is an autosomal-dominant condition associated with few symptoms other than chondrocalcinosis.  Patients always have hypocalciuria and variable (but usually mild) hypomagnesemic symptoms  Isolated recessive hypomagnesemia (IRH) with normocalcemia is an autosomal-recessive disorder in which the individuals who are affected present with symptoms of hypomagnesemia early during infancy.  Hypomagnesemia due to increased urinary magnesium excretion appears to be the only abnormal biochemical finding. IRH is distinguished from the autosomal-dominant form by the lack of hypocalciuria
  24. 24. Bartter’s syndrome  Autosomal recessive disorder involving impaired Thick Ascending Limb salt reabsorption Gitelman syndrome  autosomal recessive disorder involving loss of function of the thiazidesensitive sodium- chloride symporter located in the distal convoluted tubule
  25. 25.  Drugs like loop diuretics (including furosemide, bumetanide, and ethacrynic acid), produce large increases in magnesium excretion through the inhibition of the electrical gradient necessary for magnesium reabsorption in the TAL.  Long-term thiazide diuretic therapy also may cause magnesium deficiency due to enhanced magnesium excretion, it specifically reduces renal expression levels of the epithelial magnesium channel TRPM6
  26. 26.  Aminoglycosides are thought to induce the action of the CaSR on the TAL and DCT, producing magnesium wasting  Cisplatin and amphotericin B induced magnesium deficiency is associated with hypocalciuria, which suggests injury to the DCT  Many nephrotosic drugs also cause hypomagnesemia by increased urinary magnesium excretion, but the causes are still unknown
  27. 27. The risk of hypomagnesemia can be summarized as follows:  2% in the general population  10-20% in hospitalized patients  50-60% in intensive care unit (ICU) patients  30-80% in persons with alcoholism  25% in outpatients with diabetes
  28. 28.  A careful family history is important, particularly when acquired causes of hypomagnesemia have to be excluded  Often associated with multiple biochemical abnormalities, including hypokalemia, hypocalcemia, and metabolic acidosis.  As a result, hypomagnesemia is sometimes difficult to attribute solely to specific clinical manifestations
  29. 29.  Hypokalemia is a common event in patients with hypomagnesemia, occurring in 40-60% of cases  Partly due to underlying disorders that cause magnesium and potassium losses, including diuretic therapy and diarrhea  The mechanism for hypomagnesemia-induced hypokalemia relates to the intrinsic biophysical properties of renal outer medullary K+ (ROMK) channels mediating K+ secretion in the TAL and the distal nephron.
  30. 30.  The classic sign of severe hypomagnesemia (< 1.2 mg/dL) is hypocalcemia.  The mechanism is multifactorial.  Impaired magnesium-dependent adenyl cyclase mediates the decreased release of PTH causing hypocalcemia.  Skeletal resistance to this hormone in magnesium deficiency has also been implicated.  Hypomagnesemia also alters the normal heteroionic exchange of calcium and magnesium at the bone surface, leading to an increased bone release of magnesium ions in exchange for an increased skeletal uptake of calcium from the serum.
  31. 31.  The cardiovascular effects of magnesium deficiency include effects on electrical activity, myocardial contractility, potentiation of digitalis effects, and vascular tone  Hypomagnesemia is also recognized to cause cardiac arrhythmia like Monomorphic ventricular tachycardia, Torsade de pointes, Ventricular fibrillation.  Changes in electrocardiogram are non specific like prolongation of conduction and slight ST depression, Nonspecific T-wave changes, U waves may b seen, Prolonged QT and QU interval seen
  32. 32.  Hypertension is seen in cases of hypomagnesemia due to decrease in intracellular free magnesium that causes an increase in total peripheral resistance due to increased vascular tone and reactivity  Epidemiologic studies also show an association between magnesium deficiency and coronary artery disease (CAD)
  33. 33.  The earliest manifestations of magnesium deficiency are usually neuromuscular and neuropsychiatric disturbances, the most common being hyperexcitability.  Neuromuscular irritability, including tremor, fasciculations, tetany, Chvostek and Trousseau signs, and convulsions, may be present.  Other manifestations include Apathy, Muscle cramps, Hyperreflexia, Acute organic brain syndromes, Depression, Generalized weakness, Anorexia, Vomiting
  34. 34.  Measurement of serum magnesium  Its use in evaluating total body stores is limited Mg++ Normal sMg 1.7 – 2.5 mg/dl RBC Mg 4.04 – 6.9 mg/dl 24 hr urinary Mg 120 – 150 mg
  35. 35.  Because 30% of magnesium is bound to albumin and is therefore inactive, hypoalbuminemic states may lead to spuriously low magnesium values  Patient's protein status is an important consideration in interpreting magnesium levels.
  36. 36. GOLD STANDARD  A surrogate for direct intracellular magnesium is the measurement of magnesium retention after acute magnesium loading  An infused magnesium load - 2.4 mg/kg of lean body weight over the initial 4 h is given  A magnesium deficiency is indicated if a patient has reduced excretion (< 80% over 24 h)  Patients with malnutrition, cirrhosis, diarrhea, or long-term diuretic use typically have a positive test, whether or not they have signs or symptoms referable to magnesium depletion.
  37. 37. Excretion Analysis FEMg = [(UMg x PCr) / (PMg x UCr x 0.7)]  distinction between gastrointestinal and renal losses can be made by measuring the 24-hour urinary magnesium excretion or the FE of magnesium on a random urine specimen  daily excretion of more than 24 mg or calculated FE of magnesium above 3% in a subject with normal renal function indicates renal magnesium wasting.
  38. 38. Diet  The normal recommended daily allowance of Mg is 420 mg for men and 320 mg for women  Green vegetables such as spinach are good sources of magnesium (which is contained in the chlorophyll molecule)  Some legumes (beans and peas), nuts and seeds, and whole, unrefined grains are also good sources of magnesium
  39. 39.  oral replacement should be given in the asymptomatic patient, preferably with a sustained-release preparation  Bioavailability of oral preparations is assumed to be 33% in the absence of intestinal malabsorption • Mag-Ox 400, containing magnesium oxide • Slow-Mag, containing magnesium chloride • and Mag-Tab, containing magnesium lactate  These preparations provide about 60 – 84 mg of Mg per tablet  500mg of magnesium gluconate contain 27 mg of elemental magnesium & 1gm of magnesium sulfate contains 98 mg of elemental magnesium
  40. 40.  The hypocalcemic-hypomagnesemic patient with tetany or the patient who is suspected of having hypomagnesemic-hypokalemic ventricular arrhythmias are given 50 mEq of intravenous magnesium, given slowly over 8-24 hours  This dose can be repeated as necessary to maintain the plasma magnesium concentration above 1.0  Non emergency cases 64 mEq in first 24 hrs and 32 mEq daily for 2 to 6 days, should be continued for 1 – 2 days after serum Mg level normalises
  41. 41.  The main adverse effect of Mg replacement is hypermagnesemia due to administration at an excessive rate or excessive amount  Side effect include facial flushing, loss of deep tendon reflex, hypotension, AV block  May precipitate tetany as well in cases of hypocalcemia by increasing urinary calcium excretion  antidotes for hypermagnesemia is Intravenous calcium chloride or gluconate (1-2 ampules should be administered immediately )
  42. 42.  Patients with diuretic-induced hypomagnesemia who cannot discontinue diuretic therapy may benefit from the addition of a potassium-sparing diuretic  Amiloride, spirolonolactone and triamterene can be used.  Also useful in patient with hypomagnesemia refractory to oral therapy or in cases where oral therapy result in diarrhoea  Passive reabsorption of Mg in late distal convoluted tubule  These drugs may decrease magnesium excretion by increasing its reabsorption in the collecting tubule.  These drugs also may be useful in Bartter and Gitelman syndrome or in cisplatin nephrotoxicity.
  43. 43.  Brenner and Rector’s THE KIDNEY 9th edition  Harrison’s principles of internal medicine, 17th edition  Medscape.com
  44. 44. THANK YOU!!!!

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