Calcium homeostasis and hypercalcemia/hypocalcemia are summarized. Calcium plays important roles and is tightly regulated. Hypercalcemia can be caused by primary hyperparathyroidism, malignancy, vitamin D excess, or renal failure. Symptoms involve bones, kidneys, GI tract, and neuromuscular systems. Treatment focuses on increasing calcium excretion and inhibiting bone resorption. Hypocalcemia has causes like hypoparathyroidism, vitamin D deficiency, and alkalosis. Symptoms are weakness, tingling, and muscle spasms. Treatment provides calcium supplementation and addresses the underlying cause.

1. HYPERCALCEMIA
AND
HYPOCALCEMIA
Dr Govind Desai
1st Year Junior Resident
Department of Pulmonary Medicine

2. TOPICS TO BE COVERED
1. ROLE OF CALCIUM
2.HOMEOSTASIS OF CALCIUM
3.HYPERCALCEMIA
a)CAUSES
b)CLINICAL FEATURES
C)MANAGEMENT
4.HYPOCALCEMIA
a)CAUSES
b)CLINICAL FEATURES
c)MANAGEMENT

3. Introduction
Calcium is one of the most abundant mineral in the
human body and it has many important biological
Functions
1.2 kg to 1.4 kg of Ca is present normally in human
Body
99% - in the skeleton
Remaining amount -distributed in the ECF(0.25%) and
other soft tissues(0.75%)

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

5. Protein binding of calcium
Influenced by pH.
Metabolic acidosis decrease protein binding
increase ionized calcium.
Metabolic alkalosis increase protein
binding,decrease ionized calcium.
*Fall in pH by o.1 increases ionized calcium by 0.1
mmol/L

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)]
(Calcium in mg/dl; albumin in g/dl)

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

11. HYPERCALCEMIA

12. Hypercalcemia is defined as total serum calcium
> 10.2 mg/dl (>2.5 mmol/L )
or ionized serum calcium > 5.6 mg/dl ( >1.4 m
mol/L )
Severe hypercalemia is defined as total serum
calcium > 14 mg/dl (> 3.5 mmol/L)
Hypercalcemic crisis is present when severe
neurological symptoms or cardiac arrhythmias
are present in a patient with a serum calcium > 14
mg/dl (> 3.5 mmol/L).

14. Hypercalcemia Causes
I.Parathyroid-related
-Primary hyperparathyroidism
-Lithium therapy
II. Malignancy-related
-Solid tumor with metastases (breast)
-Solid tumor with humoral mediation of hypercalcemia (lung, kidney)
-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
-Milk-alkali syndrome

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

16. NOTE
Primary
Hyperparathyroidism and
Malignancies account for 90% of
cases of
hypercalcemia

17. Clinical Manifestations of
Hypercalcemia
Renal “stones”
Nephrolithiasis
Nephrogenic diabetes insipidus
Dehydration
Nephrocalcinosis

18. Skeleton “bones”
Bone pain
Arthritis
Osteoporosis
Osteitis fibrosa cystica in
hyperparathyroidism (subperiosteal
resorption, bone cysts)

19. Gastrointestinal “abdominal
moans”
Nausea, vomiting
Anorexia, weight loss
Constipation
Abdominal pain
Pancreatitis
Peptic ulcer disease

20. Neuromuscular “psychic groans”
Impaired concentration and memory
Confusion, stupor, coma
Lethargy and fatigue
Muscle weakness
Corneal calcification (band
keratopathy)

21. Cardiovascular
Hypertension
Shortened QT interval on ECG
Cardiac arrhythmias
Vascular calcification

22. 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 BE ASKED FOR IN HISTORY

23. INVESTIGATIONS
1. Serum Electrolytes
2. BUN,Creatinine
3. Serum Protein Electrophoresis
4. PTH levels
5. Chest Xray

24. 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

26. TREATMENT
• MEASURES TO INCREASE URINARY EXCRETION
• MEASURE TO INHIBIT BONE RESORPTION
• MEASURE TO DECREASE INTESTINAL
ABSORPTION
• SPECIFIC TREATMENT

27. 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

28. 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

29. 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

30. SPECIFIC TREATMENT
1. Discontinue drugs responsible
2. Surgical treatment in primary hyperparathyroidism
3. Specific treatment in cases of malignancy and
granulomatous conditions

31. HYPOCALCEMIA

32. HYPOCALCEMIA
A decrease in the SERUM CALCIUM
<8.5mg/dl or
IONIZED CALCIUM <3-4.4mg/dL is
termed as hypocalcemia

33. CAUSES OF HYPOCALCEMIA
1)HYPOALBUMINEMIA
2)HYPOPARATHYROIDISM
a)Post Surgical
b)Idiopathic
3)DEFECT IN VITAMIN D METABOLISM
a)Nutritional
b)Malabsorption and Drugs(anticonvulsants)
c)Liver and Renal diseases
4)MISCELLANEOUS
a)Metabolic or Respiratory Alkalosis
b)Sepsis
c)Massive Blood transfusion
d)Tumour lysis
e)Rhabdomyolysis

34. NOTE
In Hypoalbuminemia the Total
calcium levels are reduced but
ionized calcium is normal

36. HISTORY
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/PSYCOSIS

38. PHYSICAL EXAMINATION
1)CHVOSTEK’S SIGN
2)TROSSEAU’S SIGN

40. INVESTIGATIONS
• 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

42. TREATMENT
• ACUTE MANAGEMENT
• LONG TERM MANAGEMENT
• VITAMIN D SUPPLEMENTATION

43. ACUTE MANAGEMENT
• 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 < 1.9 mmol/L) or ionzied Ca < 4 mg/dl or < 1
mmol/L
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

47. Mx OF SEVERE SYMPTOMMATIC
HYPOCALCEMIA

48. LONG TERM MANAGEMENT
TREATMENT OF UNDERLYING CAUSE
ORAL ELEMENTAL CALCIUM 1-3gm /DAYGIVEN
BETWEEN MEALS
VITAMIN D SUPPLEMENTATION

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)
6)CHVOSTEK’S SIGN &TROSSEAU’S SIGN are specific physical
signs of hypocalcemia
7) AVOID RINGER LACTATE WHEN INFUSING CALCIUM
PREPARATIONS
In Hypoalbuminemia the Total
calcium levels are reduced but
ionized calcium is normal

52. REFERENCES
1. Practical Guidelines on fluid therapy-Dr
Sanjay pandya
2. Harrisons textbook of internal medicine
3. NCBI/PUBMED
4. https://en.ecgpedia.org/wiki/Electrolyte_Dis
orders
5. emedicine.medscape.com/article/766373-
workup

53. THANK YOU