The document discusses magnesium homeostasis and hypomagnesemia. It states that magnesium is predominantly stored in bone and plays a role in many enzymatic reactions. Hypomagnesemia can result from reduced intake, malabsorption, renal wasting, or redistribution from extracellular to intracellular spaces. Clinical manifestations include neuromuscular excitability, seizures, arrhythmias, and hypocalcemia. Diagnosis involves measuring serum magnesium levels and treatment consists of oral magnesium replacement or intravenous supplementation for severe cases.

1. PRESENTED BY
SHREYA JHA

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.  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. 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.  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.  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. 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. 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. 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.  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. 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. III. Related to GI Mg loss
 Diarrhea
 Vomiting and nasogastric suction
 Gastrointestinal fistulas and ostomies
 Hypomagnesemia with secondary
hypocalcemia (HSH)

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. 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. OTHERS
 Hypercalcemia
 Chronic metabolic acidosis
 Volume expansion
 Primary hyperaldosteronism
 Recovery phase of acute tubular necrosis
 Postobstructive diuresis

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.  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.  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.  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.  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.  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.  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.  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. 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.  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.  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. 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.  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.  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.  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.  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.  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.  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.  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.  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. 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. 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. 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.  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.  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.  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.  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.  Brenner and Rector’s THE KIDNEY 9th edition
 Harrison’s principles of internal medicine,
17th edition
 Medscape.com

44. THANK YOU!!!!