HYPER AND HYPOCALCEMIA

1. HYPERCALCEMIA
AND
HYPOCALCEMIA
Dr Anupam Anand JR-1
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
1.2 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)]

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. HYPERCALCE
MIA

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

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

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. NOT
E
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

23. INVESTIGATI
ONS
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. TREATME
NT
• 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. HYPOCALCE
MIA

32. HYPOCALCE
MIA
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)Rhabdomyoly

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

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/PS
YCOSIS

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

40. 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

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 < 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) 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

52. THANK
YOU