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HYPERCALCEMIA
AND
HYPOCALCEMIA
PRESENTER-Dr Anupam Anand JR-2
MODERATOR-Prof. Dr. Pankaj Bansal
Deptt. Of General Medicine
TOPICS TO BE
COVERED
1. ROLE OF CALCIUM
2.HOMEOSTASIS OF
CALCIUM
3.HYPERCALCE
MIA a)CAUSES
b)CLINICAL
FEATURES
C)MANAGEMENT
4.HYPOCALCE
MIA a)CAUSES
b)CLINICAL FEATURES
Introduction
Calcium is one of the most abundant mineral in
the human body and it has many important
biological Functions
1-2kgs of Calcium is present normally in
human body out of which 99% is in the
skeleton
Remaining amount -distributed in the
ECF(0.25%) and other soft tissues(0.75%)
Concentration in ECF-1.1-1.3mmol/L
Concentration in ICF- 100nmol/L
Distribution of calcium outside skeletal
system
In Blood , total Ca concentration is normally 8.5-10.5
mg/dl, of which approx 50% is ionized(normal value-
4.8 mg/dl)
Remainder is bound ionically to negatively
charged proteins- Predominantly albumin and
immunoglobulins or lossely complexed with
PO4 , citrate ,SO4 and other anions.
Influenced by pH.
Metabolic acidosis decrease protein binding
increase ionized calcium.
Metabolic alkalosis increase protein
As ionized form is the active form of
calcium, serum calcium levels should be
adjusted for abnormal serum albumin
levels
Corrected calcium
For every 1-g/dL drop in serum albumin
below 4 g/dL, measured serum calcium
decreases by 0.8 mg/dL.
Corrected calcium =
Measured Ca + [0.8 x (4 - measured
albumin)]
FUNCTIONS of Calcium
1. Muscle contraction
2. Neuromuscular / nerve
conduction
3. Intracellular signalling
4. Bone formation
5. Coagulation
6. Enzyme regulation
7. Maintainance of plasma
membrane stability
HYPERCALCE
MIA
Hypercalcemia is defined as total serum
calcium
> 10.2 mg/dl or ionized serum calcium > 5.6
mg/dl
Severe hypercalemia is defined as total
serum
calcium > 14 mg/dl
Hypercalcemic crisis is present when
severe neurological symptoms or cardiac
arrhythmias are present in a patient with a
serum calcium > 14 mg/dl
CAUSES FOR HYPERCALCEMIA
I.Parathyroid-related
-Primary hyperparathyroidism
-Lithium therapy
II.Malignancy-related
-Solid tumor with metastases (breast)
-Solid tumor with humoral mediation of hypercalcemia (lung, kidney)
Squamous cell Carcinoma Lung and Renal Cracinoma
-Hematologic malignancies (multiple myeloma, lymphoma, leukemia)
III.Vitamin D-related
-Vitamin D intoxication
- 1,25(OH)2D; sarcoidosis and other granulomatous diseases
IV.Associated with high bone turnover
-Hyperthyroidism
-Immobilization
-Thiazides
V.Associated with renal failure
-Severe secondary hyperparathyroidism
-Aluminum intoxication
MECHANISM OF
HYPERCALCEMIA IN
LUNG CANCERS
PRODUCTION OF HUMORAL FACTORS BY PRIMARY
TUMOR,COLLECTIVELY KNOWN AS HUMORAL
HYPERCALCEMIA OF MALIGNANCY(HHM) IN ALMOST 80 %
OF CASES
1)TUMOR PRODUCED PARATHYROID HORMONE RELATED
PROTEIN(PTHrp)
2)PRODUCTION OF 1,25 DIHYDROXYCALCITRIOL
THE REST 20% ARE DUE TO METASTASIS TO THE BONE
LEADING TO OSTEOLYSIS
NOT
E
Primary
Hyperparathyroidism and
Malignancies account for
90% of cases of
hypercalcemia
Clinical
Manifestations of
Hypercalcemia
Renal “stones”
Nephrolithiasis
Nephrogenic diabetes insipidus Dehydration
Nephrocalcinosis
Skeleton “bones” Bone pain Arthritis Osteoporosis
Osteitis fibrosa cystica in hyperparathyroidism (subperiosteal resorption, bone
cysts)
Neuromuscular “psychic groans” Impaired concentration and memory
Confusion, stupor, coma
Lethargy and fatigue Muscle weakness,Corneal calcification
(band keratopathy)
Cardiovascular
Hypertension
Gastrointestinal “abdominal moans”
Nausea, vomiting Anorexia, weight loss Constipation Abdominal pain
Pancreatitis
Peptic ulcer disease
DIAGNOSTIC
APPROACH
HISTORY AND PHYSICAL EXAMINATION
• NOTE:PATIENT WITH PRIMARY
HYPERTHYROIDISM ARE USUALLY
ASSYMTOMMATIC .
• IF HYPERCALCEMIA IS PRESENT FOR
MORE THAN 6 MONTHS PRIMARY
HYPERTHYROIDISM IS MOST CERTAIN.
• HYPERCALCEMIA WITH RENAL STONES
FAVOURS LONG DURATION AND IS UNLIKELY
DUE TO MALIGNANCY
• USE OF VITAMIN D ,CALCIUM
SUPPLEMENTATIONS AND LITHUIM SHOULD
INVESTIGATI
ONS
1. Serum Electrolytes
2. BUN,Creatinine
3. Serum Protein Electrophoresis
4. iPTH levels
5. Chest Xray
6. Vit 25(OH)D
NOTE
• As a general rule, primary
hyperparathyroidism is the etiology in
OPD patients who are assymptommatic
with Sr Ca Concentrations of <11.0
mg/dl
• On the other hand malignancy is often the
cause in symptommatic patients with
abrupt onset and serum calcium levels
higher than 14 mg/dl and survival is <6
months after detection of hypercalcemia.
TREATME
NT
• MEASURES TO INCREASE URINARY
EXCRETION
• MEASURE TO INHIBIT BONE
RESORPTION
• MEASURE TO DECREASE
INTESTINAL ABSORPTION
• SPECIFIC TREATMENT
MEASURES TO INCREASE
URINARY
EXCRETION
1) Volume Restoration expansion and saline diuresis are most
useful and effective measures to correct hypercalcemia
0.9 % NaCl is infused to correct dehydration for volume
expansion and diuresis.(almost 4-6 litres is required to cause
flushing of calcium)hence always use cautiously in HEART
FAILURE AND ELDERLY patients to avoid pulmonary oedema
2)FURUSEMIDE – Additive effect with 0.9 NS as it leads to forced
Diuresis.
3)HAEMODIALYSIS- Reserved for treatment of patients with
severe hypercalcemia and in CRF
MEASURE TO INHIBIT
BONE
RESORPTION
1)BISPHOSPHONATES- PAMIDRONATE is the most
potent and most widely used bisphosphonate
DOSAGE-60-90 mg IV over 4 hours
2)PLICAMYCIN-Rarely used owing to high toxicity
3)CALCITONIN
MOA-Inhibits bone resorption and increases urinary
excretion useful in acute crisis
DOSAGE-4IU/KG s.c 12hourly
MEASURE TO DECREASE
INTESTINAL
ABSORPTION
GLUCOCORTICOIDS
CAUSES DECREASED ABSORPTION AND
INCREASES URINARY EXCRETION
ARE EFFECTIVE IN
SARCOIDOSIS,MALIGNANCY,VIT D TOXICITY
BUT NOT IN PRIMARY HYPERPARATHYROIDISM
ORAL PHOSPHATES
HYPOCALCE
MIA
HYPOCALCE
MIA
A decrease in the SERUM
CALCIUM
<8.5mg/dl or
IONIZED CALCIUM <3-
4.4mg/dL is
termed as hypocalcemia.
CAUSES OF
HYPOCALCEMIA
TYPES OF HYPOCALCEMIA
1. CHRONIC HYPOCALCEMKIA-
CKD,VIT D DEFICIENCY
2. ACUTE HYPERCALCEMIA- SEEN
IN SEPSIS BURNS, ICU SETTINGS
WHERE CITRATED BLOOD HAS
BEEN GIVEN FREQUENTLY
3.TRANSIENT HYPOCALCEMIA-
AFTER PARATHYROID SURGERY
HISTO
RY
1. REDUCED FOOD/NUTRITIONAL
INTAKE
2. H/O SURGERY OF PARATHYROID
3. H/O RADIATION
4. H/O BLOOD TRANSFUSION
CLINICAL
FEATURES
1.WEAKNESS
2.CIRCUMORAL PARAESTHESIA
3.DISTAL EXTREMITY PARAESTHESIA
4.MUSCLE SPASM
5.CARPOPEDAL SPASM
6.TETANY
7.IRRITABILITY/DEPRESSION/PSYCHOSIS
8.INCREASED INTRACRANIAL PRESSURE WITH
PAPILLOEDEMA
9.EXTRAPYRAMIDAL SYMPTOMS –
CHOREATHETOSIS AND DYSTONIA
INVESTIGATI
ONS
• Serum Calcium (Total and Ionic
calcium)
• Serum Albumin (3.5-5.3g/dL)
• Serum Phosphorus (2.7-4.5mg/dL)
• Serum Magnesium (0.7-1.0mmol/L)
• Urinary calcium excretion (100-
250mg/24h)
• RFT
• 25-hydroxyvitamin D levels (>20ng/ml)
• Serum PTH (10-65pg/ml)
*ECG-PROLONGED QT INTERVAL
TREATME
NT
• ACUTE MANAGEMENT
• LONG TERM
MANAGEMENT
• VITAMIN D
SUPPLEMENTATION
ACUTE
MANAGEME
NT
• Goals of Therapy
• Total Serum Ca 8.6-10.2 mg/dl (2.15-
2.55 mmol/L) or
• Ionized serum Ca > 4.5 mg/dl or >
1.12 mmol/L
• Manage underlying illness
Management
Mild to moderate : Oral
supplementation
IV Calcium
Intermittent iv boluses for severe symptomatic (total
serum ca < 7.5 mg/dl or ionzied Ca < 4 mg/dl
Symptomatic hypocalcemia is an emergency
Administer 1 g Calcium chloride or Ca
Gluconate(1000 mg of elemental
calcium/10ml) iv over 10 minutes
Refractory hypocalcemia: Continuous infusion of
elemental calcium
NOTE : AVOID RINGER LACTATE WHEN INFUSING CALCIUM
PREPARATIONS
Mx OF SEVERE
SYMPTOMMATIC
HYPOCALCEMIA
LONG TERM
MANAGEMENT
TREATMENT OF UNDERLYING CAUSE
ORAL ELEMENTAL CALCIUM 1-3gm
/DAYGIVEN BETWEEN MEALS
VITAMIN D SUPPLEMENTATION
TAKE HOME MESSAGE
1)Metabolic acidosis decrease protein binding
increase ionized calcium.
Metabolic alkalosis increase protein binding,decrease ionized
calcium.
2)Corrected calcium
For every 1-g/dL drop in serum albumin below 4
g/d L, measured serum calcium decreases by 0.8mg/dL.
3) ALWAYS RULE OUT MALIGNANCY WHEN PATIENT
PRESENTS WITH ACUTE HYPERCALCEMIA
4)GLUCOCORTICOIDS ARE USEFUL IN Mx OF
HYPERCALCEMIA
TAKE HOME MESSAGE
5) In Hypoalbuminemia the Total
calcium levels are reduced but
ionized calcium is normal
6)CHVOSTEK’S SIGN &TROSSEAU’S SIGN are
specific physical
signs of hypocalcemia
7) AVOID RINGER LACTATE WHEN INFUSING
CALCIUM PREPARATIONS
THANK
YOU

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ANUPAM PPT 5.pptx

  • 1. HYPERCALCEMIA AND HYPOCALCEMIA PRESENTER-Dr Anupam Anand JR-2 MODERATOR-Prof. Dr. Pankaj Bansal Deptt. Of General Medicine
  • 2. TOPICS TO BE COVERED 1. ROLE OF CALCIUM 2.HOMEOSTASIS OF CALCIUM 3.HYPERCALCE MIA a)CAUSES b)CLINICAL FEATURES C)MANAGEMENT 4.HYPOCALCE MIA a)CAUSES b)CLINICAL FEATURES
  • 3. Introduction Calcium is one of the most abundant mineral in the human body and it has many important biological Functions 1-2kgs of Calcium is present normally in human body out of which 99% is in the skeleton Remaining amount -distributed in the ECF(0.25%) and other soft tissues(0.75%) Concentration in ECF-1.1-1.3mmol/L Concentration in ICF- 100nmol/L
  • 4. Distribution of calcium outside skeletal system In Blood , total Ca concentration is normally 8.5-10.5 mg/dl, of which approx 50% is ionized(normal value- 4.8 mg/dl) Remainder is bound ionically to negatively charged proteins- Predominantly albumin and immunoglobulins or lossely complexed with PO4 , citrate ,SO4 and other anions. Influenced by pH. Metabolic acidosis decrease protein binding increase ionized calcium. Metabolic alkalosis increase protein
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  • 8. As ionized form is the active form of calcium, serum calcium levels should be adjusted for abnormal serum albumin levels Corrected calcium For every 1-g/dL drop in serum albumin below 4 g/dL, measured serum calcium decreases by 0.8 mg/dL. Corrected calcium = Measured Ca + [0.8 x (4 - measured albumin)]
  • 9. FUNCTIONS of Calcium 1. Muscle contraction 2. Neuromuscular / nerve conduction 3. Intracellular signalling 4. Bone formation 5. Coagulation 6. Enzyme regulation 7. Maintainance of plasma membrane stability
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  • 12. Hypercalcemia is defined as total serum calcium > 10.2 mg/dl or ionized serum calcium > 5.6 mg/dl Severe hypercalemia is defined as total serum calcium > 14 mg/dl Hypercalcemic crisis is present when severe neurological symptoms or cardiac arrhythmias are present in a patient with a serum calcium > 14 mg/dl
  • 13.
  • 14. CAUSES FOR HYPERCALCEMIA I.Parathyroid-related -Primary hyperparathyroidism -Lithium therapy II.Malignancy-related -Solid tumor with metastases (breast) -Solid tumor with humoral mediation of hypercalcemia (lung, kidney) Squamous cell Carcinoma Lung and Renal Cracinoma -Hematologic malignancies (multiple myeloma, lymphoma, leukemia) III.Vitamin D-related -Vitamin D intoxication - 1,25(OH)2D; sarcoidosis and other granulomatous diseases IV.Associated with high bone turnover -Hyperthyroidism -Immobilization -Thiazides V.Associated with renal failure -Severe secondary hyperparathyroidism -Aluminum intoxication
  • 15. MECHANISM OF HYPERCALCEMIA IN LUNG CANCERS PRODUCTION OF HUMORAL FACTORS BY PRIMARY TUMOR,COLLECTIVELY KNOWN AS HUMORAL HYPERCALCEMIA OF MALIGNANCY(HHM) IN ALMOST 80 % OF CASES 1)TUMOR PRODUCED PARATHYROID HORMONE RELATED PROTEIN(PTHrp) 2)PRODUCTION OF 1,25 DIHYDROXYCALCITRIOL THE REST 20% ARE DUE TO METASTASIS TO THE BONE LEADING TO OSTEOLYSIS
  • 17. Clinical Manifestations of Hypercalcemia Renal “stones” Nephrolithiasis Nephrogenic diabetes insipidus Dehydration Nephrocalcinosis Skeleton “bones” Bone pain Arthritis Osteoporosis Osteitis fibrosa cystica in hyperparathyroidism (subperiosteal resorption, bone cysts) Neuromuscular “psychic groans” Impaired concentration and memory Confusion, stupor, coma Lethargy and fatigue Muscle weakness,Corneal calcification (band keratopathy) Cardiovascular Hypertension
  • 18. Gastrointestinal “abdominal moans” Nausea, vomiting Anorexia, weight loss Constipation Abdominal pain Pancreatitis Peptic ulcer disease
  • 19. DIAGNOSTIC APPROACH HISTORY AND PHYSICAL EXAMINATION • NOTE:PATIENT WITH PRIMARY HYPERTHYROIDISM ARE USUALLY ASSYMTOMMATIC . • IF HYPERCALCEMIA IS PRESENT FOR MORE THAN 6 MONTHS PRIMARY HYPERTHYROIDISM IS MOST CERTAIN. • HYPERCALCEMIA WITH RENAL STONES FAVOURS LONG DURATION AND IS UNLIKELY DUE TO MALIGNANCY • USE OF VITAMIN D ,CALCIUM SUPPLEMENTATIONS AND LITHUIM SHOULD
  • 20. INVESTIGATI ONS 1. Serum Electrolytes 2. BUN,Creatinine 3. Serum Protein Electrophoresis 4. iPTH levels 5. Chest Xray 6. Vit 25(OH)D
  • 21. NOTE • As a general rule, primary hyperparathyroidism is the etiology in OPD patients who are assymptommatic with Sr Ca Concentrations of <11.0 mg/dl • On the other hand malignancy is often the cause in symptommatic patients with abrupt onset and serum calcium levels higher than 14 mg/dl and survival is <6 months after detection of hypercalcemia.
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  • 24. TREATME NT • MEASURES TO INCREASE URINARY EXCRETION • MEASURE TO INHIBIT BONE RESORPTION • MEASURE TO DECREASE INTESTINAL ABSORPTION • SPECIFIC TREATMENT
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  • 26. MEASURES TO INCREASE URINARY EXCRETION 1) Volume Restoration expansion and saline diuresis are most useful and effective measures to correct hypercalcemia 0.9 % NaCl is infused to correct dehydration for volume expansion and diuresis.(almost 4-6 litres is required to cause flushing of calcium)hence always use cautiously in HEART FAILURE AND ELDERLY patients to avoid pulmonary oedema 2)FURUSEMIDE – Additive effect with 0.9 NS as it leads to forced Diuresis. 3)HAEMODIALYSIS- Reserved for treatment of patients with severe hypercalcemia and in CRF
  • 27. MEASURE TO INHIBIT BONE RESORPTION 1)BISPHOSPHONATES- PAMIDRONATE is the most potent and most widely used bisphosphonate DOSAGE-60-90 mg IV over 4 hours 2)PLICAMYCIN-Rarely used owing to high toxicity 3)CALCITONIN MOA-Inhibits bone resorption and increases urinary excretion useful in acute crisis DOSAGE-4IU/KG s.c 12hourly
  • 28. MEASURE TO DECREASE INTESTINAL ABSORPTION GLUCOCORTICOIDS CAUSES DECREASED ABSORPTION AND INCREASES URINARY EXCRETION ARE EFFECTIVE IN SARCOIDOSIS,MALIGNANCY,VIT D TOXICITY BUT NOT IN PRIMARY HYPERPARATHYROIDISM ORAL PHOSPHATES
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  • 32. HYPOCALCE MIA A decrease in the SERUM CALCIUM <8.5mg/dl or IONIZED CALCIUM <3- 4.4mg/dL is termed as hypocalcemia.
  • 34.
  • 35. TYPES OF HYPOCALCEMIA 1. CHRONIC HYPOCALCEMKIA- CKD,VIT D DEFICIENCY 2. ACUTE HYPERCALCEMIA- SEEN IN SEPSIS BURNS, ICU SETTINGS WHERE CITRATED BLOOD HAS BEEN GIVEN FREQUENTLY 3.TRANSIENT HYPOCALCEMIA- AFTER PARATHYROID SURGERY
  • 36. HISTO RY 1. REDUCED FOOD/NUTRITIONAL INTAKE 2. H/O SURGERY OF PARATHYROID 3. H/O RADIATION 4. H/O BLOOD TRANSFUSION
  • 37. CLINICAL FEATURES 1.WEAKNESS 2.CIRCUMORAL PARAESTHESIA 3.DISTAL EXTREMITY PARAESTHESIA 4.MUSCLE SPASM 5.CARPOPEDAL SPASM 6.TETANY 7.IRRITABILITY/DEPRESSION/PSYCHOSIS 8.INCREASED INTRACRANIAL PRESSURE WITH PAPILLOEDEMA 9.EXTRAPYRAMIDAL SYMPTOMS – CHOREATHETOSIS AND DYSTONIA
  • 38.
  • 39. INVESTIGATI ONS • Serum Calcium (Total and Ionic calcium) • Serum Albumin (3.5-5.3g/dL) • Serum Phosphorus (2.7-4.5mg/dL) • Serum Magnesium (0.7-1.0mmol/L) • Urinary calcium excretion (100- 250mg/24h) • RFT • 25-hydroxyvitamin D levels (>20ng/ml) • Serum PTH (10-65pg/ml) *ECG-PROLONGED QT INTERVAL
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  • 42. TREATME NT • ACUTE MANAGEMENT • LONG TERM MANAGEMENT • VITAMIN D SUPPLEMENTATION
  • 43. ACUTE MANAGEME NT • Goals of Therapy • Total Serum Ca 8.6-10.2 mg/dl (2.15- 2.55 mmol/L) or • Ionized serum Ca > 4.5 mg/dl or > 1.12 mmol/L • Manage underlying illness
  • 44. Management Mild to moderate : Oral supplementation IV Calcium Intermittent iv boluses for severe symptomatic (total serum ca < 7.5 mg/dl or ionzied Ca < 4 mg/dl Symptomatic hypocalcemia is an emergency Administer 1 g Calcium chloride or Ca Gluconate(1000 mg of elemental calcium/10ml) iv over 10 minutes Refractory hypocalcemia: Continuous infusion of elemental calcium
  • 45. NOTE : AVOID RINGER LACTATE WHEN INFUSING CALCIUM PREPARATIONS
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  • 48. LONG TERM MANAGEMENT TREATMENT OF UNDERLYING CAUSE ORAL ELEMENTAL CALCIUM 1-3gm /DAYGIVEN BETWEEN MEALS VITAMIN D SUPPLEMENTATION
  • 49.
  • 50. TAKE HOME MESSAGE 1)Metabolic acidosis decrease protein binding increase ionized calcium. Metabolic alkalosis increase protein binding,decrease ionized calcium. 2)Corrected calcium For every 1-g/dL drop in serum albumin below 4 g/d L, measured serum calcium decreases by 0.8mg/dL. 3) ALWAYS RULE OUT MALIGNANCY WHEN PATIENT PRESENTS WITH ACUTE HYPERCALCEMIA 4)GLUCOCORTICOIDS ARE USEFUL IN Mx OF HYPERCALCEMIA
  • 51. TAKE HOME MESSAGE 5) In Hypoalbuminemia the Total calcium levels are reduced but ionized calcium is normal 6)CHVOSTEK’S SIGN &TROSSEAU’S SIGN are specific physical signs of hypocalcemia 7) AVOID RINGER LACTATE WHEN INFUSING CALCIUM PREPARATIONS

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