DISORDERS OF
CALCIUM
DR SRUDI
2ND YR PG
CALCIUM
• Calcium is the most abundant electrolyte in the human body (out of which
99% is present in the bone and remaining 1% in ECF)
• The total plasma calcium concentration is divided into 3 fractions:
*45% physiologically active ionized form
*40% bound to albumin
*15% bound to multiple organic and inorganic anions such as phosphate,
lactate, citrate.
• The calcium ion plays a critical role in normal cellular function and signaling,
regulating diverse physiologic processes such as neuromuscular signaling,
cardiac contractility, hormone secretion, and blood coagulation
• Normal level of total calcium :9-10 mg/dl ; ionized calcium – 4.6 -5mg/dl
Extracellular calcium concentrations are
maintained within an exquisitely narrow range(4.6
to 5.1mg/dl),for a optimal neuromuscular
function,through a series of feedback mechanisms
that involve parathyroid hormone (PTH) and the
active vitamin D metabolite 1,25-
dihydroxyvitamin D [1,25(OH)2 D]. These
feedback mechanisms are orchestrated by
integrating signals between the parathyroid glands,
kidney, intestine and bone.
HYPOCALCEMIA
CLINICAL MANIFESTATION:
• Mild and chronic hypocalcemia is usually asymptomatic.
• Neuromuscular and cardiovascular symptoms are usually predominant
with moderate to severe hypocalcemia.
• The clinical manifestation include:
*Paresthesia of toes ,fingers, circumoral region
* Tetany
* Seizures
* Hyper reflexia
• Clinically we can elicit two signs namely, chovstek sign and trousseau’s
sign
Other manifestation include:
• Confusion
• Hypotension
• Bradycardia
• Prolongation of QT interval
• Brochospasm
• Laryngospasm
• Decreased cardiac output
• Ventricular ectopic activity
PREDISPOSING FACTORS:
• Magnesium deficiency- hypomagnesiumia can impair PTH secretion
• Pseudo hypocalcaemia- associated with albumin depletion
• Sepsis – mechanisms involved in hypocalcemia is unclear . Many patients
have found to have elevated levels of procalcitonin. Some suggests that
this procalcitonin and it’s precursor may be the cause of hypocalcemia in
sepsis.
• Blood transfusion
• Pancreatic
• Renal failure
• Drugs- heparin, aminoglycosides
DIAGNOSTIC APPROACH
• To measure serum calcium (specifically to measure ionized
calcium)
• Other than calcium ; albumin , magnesium and phosphate
levels should also be determined
• To know the cause of hypocalcemia, levels of PTH and
levels of 25 hydroxy vitamin D (for nutritional causes ) and
1,25 Dihydroxy vitamin D levels (to rule out renal
insufficiency and vitamin D resistance)
TREATMENT:
• Treatment of hypocalcemia depends on its severity, rapid onset and it’s
accompanying complications.
• Acute symptomatic hypocalcemia is treated with calcium gluconate
• Dosing Regimen :
• A bolus dose of 200 mg elemental calcium (diluted in 100 mL isotonic saline
and given over 5–10 minutes) should raise the total serum calcium by 0.5
mg/dL, but levels will begin to fall after 30 minutes .
• Therefore, the bolus dose of calcium should be followed by a continuous
infusion at a dose rate of 1–2 mg/kg/hr (elemental calcium) for at least 6 hours.
• Individual responses will vary, so calcium dosing should be guided by the level
of ionized calcium in blood
• Two formulation of calcium is available – calcium gluconate and calcium
chloride
• Calcium gluconate is preferred over Calcium chloride because it is less
irritating when injected and has low osmolarity.
• Accompanying hypomagnesiumia if present should be corrected with magnesium
sulfate infusion -2gm bolus through IV.
• If symptomatic hypocalcemia present is due to hyperphosphatemia, correction
should be withheld because it may cause rebound hypercalcaemia.
• If hypocalcemia is due to certain chelating agents then consider dialysis with high
calcium dialysate.
• Asymptomatic or chronic hypocalcemia can be corrected with oral calcium
supplements (1000–1500 mg/day elemental calcium in divided doses) and either
vitamin D2 or D3 (25,000–100,000 U daily) or calcitriol [1,25(OH)2 D, 0.25–2
μg/day]
• Nutritional vitamin D deficiency generally responds to relatively low doses of
vitamin D (50,000 IU, 2–3 times per week for several months), whereas vitamin D
deficiency due to malabsorption may require much higher doses (100,000 IU/d or
more).
• PTH (1-84) (Natpara) is now approved by the Food and Drug Administration for the
treatment of refractory hypoparathyroidism
HYPERCALCAEMIA
• Hypercalcaemia – corrected calcium more than 10.3mg/dl or ionized
calcium more than 5.1mg/dl.
• Excess PTH production, which is not appropriately suppressed by increased
serum calcium concentrations, occurs in primary neoplastic disorders of the
parathyroid glands (parathyroid adenomas; hyperplasia; or, rarely,
carcinoma) that are associated with increased parathyroid cell mass and
impaired feedback inhibition by calcium.
• Inappropriate PTH secretion for the ambient level of serum calcium also
occurs in familial hypocalciuric hypercalcemia (FHH), which is an autosomal
dominant syndrome(impairs extracellular calcium sensing by the
parathyroid glands and the kidneys, leading to inappropriate PTH secretion
and increased renal tubular calcium reabsorption)
• Many solid tumors produce PTH-related peptide (PTHrP), which
shares homology with PTH and binds the PTH receptor, thus
mimicking effects of PTH on bone and the kidney ( PTH levels are
suppressed by high calcium levels)
• Hypercalcemia associated with granulomatous disease (e.g.,
sarcoidosis) or lymphomas is caused by enhanced conversion of
25(OH)D to the potent 1,25(OH)2 D
• Disorders that directly increase calcium mobilization from bone, such
as hyperthyroidism or osteolytic metastases, also lead to
hypercalcemia with suppressed PTH secretion as does exogenous
calcium overload, as in milk-alkali syndrome, or total parenteral
nutrition with excessive calcium supplementation.
Clinical manifestation
• Clinical manifestation are usually seen in levels above 12mg/dl
• Patient may complain vague neuropsychiatric complaint like difficulty in
concentrations, Confusion, personality changes, in severe cases depression,
stupor and coma
• Gastrointestinal symptoms- Nausea, vomiting, constipation, ileum,
occasionally pancreatic
• Cardiovascular symptoms: Hypotension, Hypovolemia, shortened QT
interval ,AV block
• Renal symptoms: polyuria , nephrocalcinosis
• Bone pain, pathological fracture
DIAGNOSTIC APPROACH
• Serum calcium levels
• Serum albumin levels
• Serum PTH levels
• Renal function test
• Serum phosphate levels
• Test for detecting Serum PTH related peptide levels
• Serum vitamin D levels
TREATMENT
THANK YOU!!
