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PRESENTED BY
DR.ZANNATUL FIRDAUS
MD RESIDENT
PHASE A
INTERNAL MEDICINE
TOPIC:
HYPOCALCEMIA & HYPERCALCEMIA
CALCIUM
• Calcium, a divalent cation ,one of the most abundant mineral in the
human body that plays a critical role in numerous biological
functions.
• Normal total serum calcium (Ca+2) concentration is 8.8-10.4 mg/dl,
and this is equivalent to 4.4-5.2 mEq/L or 2.2-2.6 mmol/L
• 99% in the skeleton
• Remaining amount distributed in serum .
Serum Ca+2 exists in three forms:
A. ionized (free; 48%),
B. protein-bound (mostly to albumin and less to globulins; 45%),
C. complexed (bound to citrate, oxalate, carbonate, and
phosphate; 7%),
Both ionized and complexed Ca+2 are diffusible (ultrafilterable by
the kidney), while protein-bound Ca+2 is not
CONT.
PROTEIN BINDING OF CALCIUM
• mostly to albumin and less to globulins; 45%
• Intracellular Ca+2 is bound to calmodulin and other Ca+2-binding
proteins.
• Hypoalbuminemia will lead to hypocalcemia due to a decrease in
protein-bound Ca+2
• Influenced by pH.
Metabolic acidosis decrease protein binding,increase ionized
calcium.
Metabolic alkalosis increase protein binding,decrease ionized
calcium.
• Fall in pH by 0.1, increase ionized calcium by 0.05 mmol/L.
CONT
• As ionized form is the active form of calcium,serum calcium level should be
adjusted for abnormal serum albumin level.
Corrected calcium
• For every 1-g/dL drop in serum albumin below 4 g/dL, measured serum
calcium decrease by 0.8 mg/dL
• Corrected calcium = measured calcium(mg/dl) + 0.8( 4 - measured albumin)
• Calcium in mg/dl, Albumin in g/dL
FUNCTION OF CALCIUM
• Calcium plays very important role.
• Componant of bone and teeth.
• Responsible for the excitation & contraction of muscle cell.
• Essential blood clotting factor.
HORMONE INVOLVE IN CALCIUM
HOMEOSTASIS:
11
CALCIUM, PTH, AND VITAMIN D FEEDBACK
LOOPS
NORMAL BLOOD Ca
RISING BLOOD Ca
FALLING BLOOD Ca
SUPPRESS PTH
STIMULATE PTH
BONE RESORPTION
URINARY LOSS
1,25(OH)2 D PRODUCTION
BONE RESORPTION
URINARY LOSS
1,25(OH)2 D PRODUCTION
INVESTIGATION IN A CASE OF CA
DISORDER
• Serum calcium (ionized/ total)
• Phosphate
• Magnesium
• Alkaline phosphatase
• Renal function
• iPTH
• 25(OH)D.
HYPOCALCEMIA
CAUSE:
CONT
The most common cause of hypocalcaemia is a low serum albumin with normal
ionised calcium concentration.
Conversely, ionised calcium may be low in the face of normal total serum calcium
in patients with alkalosis: for example, as a result of hyperventilation.
HYPOPARATHYROIDISM
• Deficient secretion of PTH
• Manifests itself biochemically by hypocalcemia, hyperphosphatemia
diminished or absent circulating iPTH
• Clinically the symptoms of neuromuscular hyperactivity.
PSEUDOHYPOPARATHYROIDISM
Target organ insensitivity to PTH (bone /
kidney)
• Hypocalcemia
• Hyperphosphatemia
• Elevated PTH
• in association with short stature, short
fourth metacarpals and metatarsals,
rounded face, obesity and
subcutaneous calcifcation
HYPOMAGNESEMIA
Hypocalcaemia may also develop as a result of magnesium depletion
and should be considered in patients with
• malabsorption
• diuretic or
• proton pump inhibitor therapy,
• history of alcohol excess.
MECHANISM
• Impairing the ability of the parathyroid glands to secrete PTH (resulting in PTH
concentrations that are low or inappropriately in the reference range)
• impair the actions of PTH on bone and kidney.
CLINICAL FEATURES:
• Paraesthesia
• Tetany
• Hyperventilation
• Adrenergic symptoms
• Chvostek sign
• Trousseau sign
• Extrapyramidal signs (due to
basal ganglia calcification)
• Grandmal epilepsy
• Cataract
• Convulsion
• Stridor
• Papillodema
• Psychosis
Mild hypocalcaemia is often asymptomatic
TETANY
Tetany can occur in profound reductions in serum calcium,. This is characterised by
muscle spasms due to increased excitability of peripheral nerves. Children are more
liable to develop tetany than adults .
It present with a characteristic triad of
• carpopedal spasm,
• stridor and
• convulsions,
Although one or more of these may be found independently of the others. In
carpopedal spasm, the hands adopt a characteristic position with flexion of the
metacarpophalangeal joints of the fingers and adduction of the thumb (‘main
d’accoucheur’). Pedal spasm can also occur but is less frequent.
Trousseau’s sign:
• inflation of a sphygmomanometer cuff on the upper arm to more than the
systolic blood pressure is followed by carpal spasm within 3 minutes.
• Latent tetany may be detected by eliciting Trousseau’s sign.
Chvostek’s sign:
• tapping over the branches of the facial nerve as they emerge from the
parotid gland produces twitching of the facial muscles.
• Less specific
ECG
• Long QT interval with normal T waves
• Prolongation of the ST segment with little shift from the baseline
BASAL GANGLIA CALCIFICATION
HYPOPARATHYROID
ISM
PSEUDO
HYPOPARATHYROIDISM
SENILE
TREATMENT
• The mainstay of treatment is a combination of oral calcium with
pharmacological doses of vitamin D or its potent analogues.
• Phosphate restriction in diet may also be useful with or without
aluminum hydroxide gel to lower serum phosphate level.
HYPOCALCEMIA: CHRONIC THERAPY
• Oral calcitriol 0.25-2 mcg/day
• Calcium carbonate 1-2 gm BID-TID
HYPERCALCEMIA
CAUSE
• Primary hyperparathyroidism and malignant hypercalcaemia are by far the
most commom. Familial hypocalciuric hypercalcaemia (FHH) is a rare but
important cause.
• Lithium may cause hyperparathyroidism by reducing the sensitivity of the
calcium-sensing receptor.
CONT
• Classic symptoms of hypercalcemia are described by the adage
• ‘bones,
• stones and
• abdominal groans’.
but few patients present in this way nowadays
• Patients with malignant hypercalcemia can have a rapid onset of symptoms and may
have clinical features that help to localize the tumor.
• About 50% of patients with primary hyperparathyroidism are asymptomatic
• 5% of first stone formers and 15% of recurrent stone formers have primary
hyperparathyroidism.Hypertension is a common feature of
hyperparathyroidism.
SYMPTOMS AND SIGNS OF HYPERCALCEMIA:
• polyuria and polydipsia,
• renal colic,
• lethargy,
• anorexia,nausea, dyspepsia and peptic ulceration,
• constipation,
• depression,
• drowsiness and
• impaired cognition
CONT
INVESTIGATION
• The most discriminatory investigation is measurement of PTH.
• If PTH levels are detectable or elevated in the presence of hypercalcaemia,
then primary hyperparathyroidism is the most likely diagnosis.
• High plasma phosphate and alkaline phosphatase accompanied by renal
impairment suggest tertiary hyperparathyroidism.
• Hypercalcaemia may cause nephrocalcinosis and renal tubular impairment,
resulting in hyperuricaemia and hyperchloraemia.
• FHH can be con rmed by screening family members for hypercalcaemia
and/or identifying an inactivating mutation in the gene encoding the
calcium-sensing receptor,as it has similar biochemical picture to primary
hyperparathyroidism but typically have low urinary calcium excretion(a
ratio of urinary calcium clearance to creatinine clearance of <0.01).
ECG
39
Short QT interval with shortening of ST segment.
Radiology of hyperparathyroidism
MANAGEWMENT
DIAGNOSIS
The presence of established hypercalcaemia in more than one serum
measurement accompanied by elevated immunoreactive PTH is characteristic
(iPTH).
SURGICAL TREATMENT
Surgical treatment should be considered in all cases with established
diagnosis of primary hyperparthyroidism.
LOCALIZATION OF PARATHYROID GLAND
TECHNIQUE
PARATHYROID LOCALIZATION
Sestamibi scans
After 1 hour, there is uptake in the thyroid gland (thick arrow) and
3 hours, uptake is evident only in the parathyroid (thin arrow).
99mTc-sestamibi scan of a patient with primary hyperparathyroidism
secondary to a parathyroid adenoma
Parathyroid - 99mTechnetium/201Thallium subtraction scan
INDICATIONS OF SURGERY
• Symptomatic hypercalcemia
• Asymptomatic significant hypercalcemia (corrected serum calcium > 2.85 mmol/L or >
11.4 mg/dL
• Complications of hypercalcemia –
peptic ulceration
renal stones
renal impairment (CCR < 30)
osteoporosis (T score any site <-2.5)
• Urinary ca excretion > 400 mg/day
• Aged less than 50 years,
• If PTH is low and no other cause is apparent, then malignancy with or without
bony metastases is likely.
• PTH-related peptide, which is often responsible for the hypercalcaemia
associated with malignancy, is not detected by PTH assays, but can be
measured by a specifc assay (although this is not usually necessary).
• Unless the source is obvious, the patient should be screened for malignancy
with a chest X-ray, myeloma screen and CT.
HYPERCALCEMIA OF MALIGNANCY
THANK YOU

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Calcium (1)............................................pdf

  • 1. PRESENTED BY DR.ZANNATUL FIRDAUS MD RESIDENT PHASE A INTERNAL MEDICINE
  • 3. CALCIUM • Calcium, a divalent cation ,one of the most abundant mineral in the human body that plays a critical role in numerous biological functions. • Normal total serum calcium (Ca+2) concentration is 8.8-10.4 mg/dl, and this is equivalent to 4.4-5.2 mEq/L or 2.2-2.6 mmol/L • 99% in the skeleton • Remaining amount distributed in serum .
  • 4. Serum Ca+2 exists in three forms: A. ionized (free; 48%), B. protein-bound (mostly to albumin and less to globulins; 45%), C. complexed (bound to citrate, oxalate, carbonate, and phosphate; 7%), Both ionized and complexed Ca+2 are diffusible (ultrafilterable by the kidney), while protein-bound Ca+2 is not CONT.
  • 5.
  • 6. PROTEIN BINDING OF CALCIUM • mostly to albumin and less to globulins; 45% • Intracellular Ca+2 is bound to calmodulin and other Ca+2-binding proteins. • Hypoalbuminemia will lead to hypocalcemia due to a decrease in protein-bound Ca+2 • Influenced by pH. Metabolic acidosis decrease protein binding,increase ionized calcium. Metabolic alkalosis increase protein binding,decrease ionized calcium. • Fall in pH by 0.1, increase ionized calcium by 0.05 mmol/L.
  • 7. CONT • As ionized form is the active form of calcium,serum calcium level should be adjusted for abnormal serum albumin level. Corrected calcium • For every 1-g/dL drop in serum albumin below 4 g/dL, measured serum calcium decrease by 0.8 mg/dL • Corrected calcium = measured calcium(mg/dl) + 0.8( 4 - measured albumin) • Calcium in mg/dl, Albumin in g/dL
  • 8. FUNCTION OF CALCIUM • Calcium plays very important role. • Componant of bone and teeth. • Responsible for the excitation & contraction of muscle cell. • Essential blood clotting factor.
  • 9.
  • 10. HORMONE INVOLVE IN CALCIUM HOMEOSTASIS:
  • 11. 11 CALCIUM, PTH, AND VITAMIN D FEEDBACK LOOPS NORMAL BLOOD Ca RISING BLOOD Ca FALLING BLOOD Ca SUPPRESS PTH STIMULATE PTH BONE RESORPTION URINARY LOSS 1,25(OH)2 D PRODUCTION BONE RESORPTION URINARY LOSS 1,25(OH)2 D PRODUCTION
  • 12. INVESTIGATION IN A CASE OF CA DISORDER • Serum calcium (ionized/ total) • Phosphate • Magnesium • Alkaline phosphatase • Renal function • iPTH • 25(OH)D.
  • 15. CONT The most common cause of hypocalcaemia is a low serum albumin with normal ionised calcium concentration. Conversely, ionised calcium may be low in the face of normal total serum calcium in patients with alkalosis: for example, as a result of hyperventilation.
  • 16. HYPOPARATHYROIDISM • Deficient secretion of PTH • Manifests itself biochemically by hypocalcemia, hyperphosphatemia diminished or absent circulating iPTH • Clinically the symptoms of neuromuscular hyperactivity.
  • 17. PSEUDOHYPOPARATHYROIDISM Target organ insensitivity to PTH (bone / kidney) • Hypocalcemia • Hyperphosphatemia • Elevated PTH • in association with short stature, short fourth metacarpals and metatarsals, rounded face, obesity and subcutaneous calcifcation
  • 18. HYPOMAGNESEMIA Hypocalcaemia may also develop as a result of magnesium depletion and should be considered in patients with • malabsorption • diuretic or • proton pump inhibitor therapy, • history of alcohol excess.
  • 19. MECHANISM • Impairing the ability of the parathyroid glands to secrete PTH (resulting in PTH concentrations that are low or inappropriately in the reference range) • impair the actions of PTH on bone and kidney.
  • 20. CLINICAL FEATURES: • Paraesthesia • Tetany • Hyperventilation • Adrenergic symptoms • Chvostek sign • Trousseau sign • Extrapyramidal signs (due to basal ganglia calcification) • Grandmal epilepsy • Cataract • Convulsion • Stridor • Papillodema • Psychosis Mild hypocalcaemia is often asymptomatic
  • 21. TETANY Tetany can occur in profound reductions in serum calcium,. This is characterised by muscle spasms due to increased excitability of peripheral nerves. Children are more liable to develop tetany than adults . It present with a characteristic triad of • carpopedal spasm, • stridor and • convulsions, Although one or more of these may be found independently of the others. In carpopedal spasm, the hands adopt a characteristic position with flexion of the metacarpophalangeal joints of the fingers and adduction of the thumb (‘main d’accoucheur’). Pedal spasm can also occur but is less frequent.
  • 22. Trousseau’s sign: • inflation of a sphygmomanometer cuff on the upper arm to more than the systolic blood pressure is followed by carpal spasm within 3 minutes. • Latent tetany may be detected by eliciting Trousseau’s sign.
  • 23. Chvostek’s sign: • tapping over the branches of the facial nerve as they emerge from the parotid gland produces twitching of the facial muscles. • Less specific
  • 24. ECG • Long QT interval with normal T waves • Prolongation of the ST segment with little shift from the baseline
  • 26.
  • 27. TREATMENT • The mainstay of treatment is a combination of oral calcium with pharmacological doses of vitamin D or its potent analogues. • Phosphate restriction in diet may also be useful with or without aluminum hydroxide gel to lower serum phosphate level.
  • 28. HYPOCALCEMIA: CHRONIC THERAPY • Oral calcitriol 0.25-2 mcg/day • Calcium carbonate 1-2 gm BID-TID
  • 29.
  • 31. CAUSE
  • 32. • Primary hyperparathyroidism and malignant hypercalcaemia are by far the most commom. Familial hypocalciuric hypercalcaemia (FHH) is a rare but important cause. • Lithium may cause hyperparathyroidism by reducing the sensitivity of the calcium-sensing receptor. CONT
  • 33. • Classic symptoms of hypercalcemia are described by the adage • ‘bones, • stones and • abdominal groans’. but few patients present in this way nowadays • Patients with malignant hypercalcemia can have a rapid onset of symptoms and may have clinical features that help to localize the tumor. • About 50% of patients with primary hyperparathyroidism are asymptomatic • 5% of first stone formers and 15% of recurrent stone formers have primary hyperparathyroidism.Hypertension is a common feature of hyperparathyroidism. SYMPTOMS AND SIGNS OF HYPERCALCEMIA:
  • 34. • polyuria and polydipsia, • renal colic, • lethargy, • anorexia,nausea, dyspepsia and peptic ulceration, • constipation, • depression, • drowsiness and • impaired cognition CONT
  • 35. INVESTIGATION • The most discriminatory investigation is measurement of PTH. • If PTH levels are detectable or elevated in the presence of hypercalcaemia, then primary hyperparathyroidism is the most likely diagnosis. • High plasma phosphate and alkaline phosphatase accompanied by renal impairment suggest tertiary hyperparathyroidism. • Hypercalcaemia may cause nephrocalcinosis and renal tubular impairment, resulting in hyperuricaemia and hyperchloraemia. • FHH can be con rmed by screening family members for hypercalcaemia and/or identifying an inactivating mutation in the gene encoding the calcium-sensing receptor,as it has similar biochemical picture to primary hyperparathyroidism but typically have low urinary calcium excretion(a ratio of urinary calcium clearance to creatinine clearance of <0.01).
  • 36.
  • 37.
  • 38.
  • 39. ECG 39 Short QT interval with shortening of ST segment.
  • 41.
  • 43. DIAGNOSIS The presence of established hypercalcaemia in more than one serum measurement accompanied by elevated immunoreactive PTH is characteristic (iPTH).
  • 44. SURGICAL TREATMENT Surgical treatment should be considered in all cases with established diagnosis of primary hyperparthyroidism.
  • 45. LOCALIZATION OF PARATHYROID GLAND TECHNIQUE
  • 46.
  • 48. After 1 hour, there is uptake in the thyroid gland (thick arrow) and 3 hours, uptake is evident only in the parathyroid (thin arrow). 99mTc-sestamibi scan of a patient with primary hyperparathyroidism secondary to a parathyroid adenoma
  • 50. INDICATIONS OF SURGERY • Symptomatic hypercalcemia • Asymptomatic significant hypercalcemia (corrected serum calcium > 2.85 mmol/L or > 11.4 mg/dL • Complications of hypercalcemia – peptic ulceration renal stones renal impairment (CCR < 30) osteoporosis (T score any site <-2.5) • Urinary ca excretion > 400 mg/day • Aged less than 50 years,
  • 51. • If PTH is low and no other cause is apparent, then malignancy with or without bony metastases is likely. • PTH-related peptide, which is often responsible for the hypercalcaemia associated with malignancy, is not detected by PTH assays, but can be measured by a specifc assay (although this is not usually necessary). • Unless the source is obvious, the patient should be screened for malignancy with a chest X-ray, myeloma screen and CT. HYPERCALCEMIA OF MALIGNANCY
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  • 53.