·       LABORATORY VALUES ARE THAT OF TOTAL SERUM CALCIUM

(IONIZED+COMPLEXED+ALBUMIN (80%)/ GLOBULIN (20%) BOUND) N=8.8-

10.2 mg%

·       % age of protein-bound Calcium= 80 x albumin (g/Dl) + 20X globulin (g/Dl ) + 3

·       Conversion for calcium values in mg% = 2 x meq/L = 4x mmol/L

·       Out of these, only the ionized component is necessary for the neuromuscular events, the component which is acted upon influences the Parathormone activity and it is a deficiency/excess of this component solely which is responsible for theclinical manifestations observed.

·       SERUM CALCIUM TO BE GIVEN AS A FASTING SAMPLE (Because of the falsely highlevels, postprandially due to prompt intestinal absorption.)

·       SAMPLE SHOULD NOT BE COLLECTED WITH A TOURNIQUET IN PLACE. (Falsely

highCalcium due to hypoxia-muscle cells extruding calcium from its sarcoplasmic reticulum- T tubule system into the ECF.)

·       CHANGES IN Ph, (bicarbonate and citrates), being an acute event, change the

ionized component of calcium without changing the total serum calcium, e.g.

In alkalosis, more albumin is ionized, more of calcium binds to it, and therefore, the ionized fraction falls resulting in a hypocalcemic manifestation in the presence of normaltotal serum calcium. The reverse takes place in acidosis.

In the physiological range, ionized calcium decreases by 0.5mmol/L for each 0.1 unit increases in pH (i.e alkalosis)

·       CHANGES IN SERUM PROTEIN (mainly albumin) , being gradual event, changes the total serum calcium without changing the ionized component, e.g

In hypoalbuminemia, as the ionized fraction of the total calcium tends to rise due to less available albumin to bind to calcium, it is subject to counter regulatory influenceof the Parathormone, which brings it down. In effect, the measured total serum calcium falls through the ionized calcium is constant (which is our field of concern). Therefore we have to correct for hypo/hyper proteinemic states.

Formula to be used :-

 Each fall/rise in serum albumin level by 1.0 g/dl (beyond the normal range of 4-5g/dl) is associated with a fall or rise of serum calcium concentration of approximately 0.8 mg/dl.

ACTUAL CALCIUM = MEASURED CALCIUM + (4 – SERUM ALBUMIN) x F where F= 0.8

for mg% 0.4 for meq/L, 0.2 for mmol/L

HYPOCALCEMIA

 Definition :- Serum calcium (in the presence of normal proteins ) < 8.8 mg% (2.2 mmol/L, 4.4 meq/L). This can be caused by either reduced ionized or protein bound calcium.

Causes :- with (lab. Interpretation of Calcium, Phosphates and Alkaline phosphatase)

·       Hypoparathyroidism, pseudohypoparathyroidism, (L Ca, H p, N alkphos)

·       Vitamin D deficiency/malabsorption. (L Ca, L p, N Alkphos)

·       In acute care settings, excessive calcium sequestration (burns, toxic shock, septicemia, pancreatitis)

·       Renal osteodystrophy (secondary hyperparathyroidism) ( L Ca, H p, H Alkphos)

·       Reduced ionized calcium with normal total serum calcium (citrate toxicity in massive transfusion, and respiratory alkalosis with PaCO2 < 21 mm of Hg, Hypomahnesemia.)

·       Hypomagnesaemia

(L= low, H= high, N=normal, Ca= calcium, p= phosphates.)

Clinical features :-

 Tetany of muscles of the extremely and the larynx

TROSSEAUS sign :- inflate BP cuff above systolic and maintain at that for 3minutes- to look for carpo-pedal spasm.

CHVOSTEK’S contraction of ipsilateral facial muscle by tapping over the facialnerve at the angle of the jaw.

Physiology of all these tests depend on the fact that neuro-muscular tissue is irritable in the presence of hypocalcemia and using a BP cuff to occlude bloodsupply and make the muscles ischemic (TROUSSEAU’S ) or to tap on the facial nerve ( CHVOSTEK’S) are further insults or precipitating factors to elicit the tetany over a localized group of muscles.

Other features include circumoral paresthesiae, or fingertip tingling/burning, cramps, mental changes

(hallucination/confusion) areflexia, seizures and hypotension.

Chronic hypocalcemia can present with cataracts, papilloedema, basal ganglia calcification, alopecia, coarse dry skin.

Treatment :- for acute hypocalcemia

·       IV calcium in symptomatic patients.

·       CALCIUM CHLORIDE has 3 x the CALCIUM CONTENT in mmol. Than CALCIUM GLUCONATE for equal CONCENTRATIONS and VOLUMES.

·       10 ml of 10% Calcium gluconate IV over 3-5 mins.

·       In severe cases, IV infusion of calcium gluconate 10%, 100 ml in 1000ml of 5% dextrose over 3-4 h. May need repetition of such supplements.

·       In post parathyroidectomy hypocalcemia IV infusion of calcium gluconate 10%, 50 ml in 500 ml of 5% dextrose over Q12 hrly.

For chronic hypocalcemia

·       Oral calcium supplements :- Tab.Sandocal (Calcium carbonate) 1 OD-TID.

HYPERCALCEMIA

 Definition :- Total serum calcium > 10.2mg (2.55mmol/L, 5.1 meq/L) or increased ionized Calcium.

Causes :-

·       A and D Vitamin toxicity, Alkali-milk syndrome.

·       B one disease (Pagent’s disese)

·       Cancers (Lymphoma/lithium)

·       Drugs (thiazides, lithium)

·       Endocrine (thyrotoxicosis, phaeochromocytoma, Addison’s disease, Acromegaly, VIPomas)

·       Factitious (Haemoconcentration, postprandial)

·       Granulomas (Tb, sarcoid)

·       Hyperparathyroidism (primary, tertiary)

(Secondary hyperparathyroidism has a low serum calcium, i.e in Renalosteodystropy. A persisting secondary hyperparathyroidism can go on to tertiary hyperparathyroidism due to chronic stimulus resulting in autonomy.)

Clinical Features : usually with serum calcium >3.0mmol/L (12mg%, 6meq/L)

·       GIT-anorexia, nausea, constipation, vomiting, pancreatitis, peptic ulcers

·       URINARY- polyuria, polydipsia (Nephrogenic DI), nephrocalcinosis,

·       CNS- depression, psychosis, apathy, somnolence, confusion, coma

·       MUSCULOSKELETAL- arthralgia, myalgia, hypotonia, weakness.

Popularly known as – ‘BONES (painful), GROANS (abdominal), MOANS (psychic)’ Investigations :- Ca, Mg, HCO3, albumin, Phosphate, urinary hydroxyproline, Alkaline phosphatase, screening for malignancy with necessary lab investigations and imaging techniques.

Interpretation of lab. Results :-

Summarizing, single diagnosis to be considered based on various combinations of the lab. Tests :-

High Calcium-Low Phosphate-High Alkaline phosphatase….. Hyperparathyroidism

High Calcium- normal phosphates- High Alkaline phosphatase… metatastic carcinoma

High (mild) calcium-normal phosphates- Very Alkaline phosphatase… Pagets,

High       calcium-normal         phosphates-        moderately               high/normal               Alkaline

phosphatase…. Sarcoidosis.

High Calcium-High Phosphates-high bicarbonate… Milk-alkali syndrome,

High Calcium :- High Phosphates- Low/Normal Alkaline phosphatase….Vitamin D intoxication,Multiple myeloma

High calcium- High Phosphates- High Alkaline phosphatase…thyrotoxicosis.

Management :-

·       Correct dehydration (which occurs due to NDI in hypercalcemia). A central line is preferred;monitor intake-output. Initially 2L of fluid is loaded (1L of 0.9%Nacl and 1L of 5% dextrose) followed by IV Frusemide 80 mg 2-4hly. The urine output is replaced by alternating 0.9% NS and 5%D upto 6L/day. Significant fall in calcium occurs in the first 4h. DO NOT USE DIURESE WITHOUT ENSURING ADEQUATE VASCULAR FILLING.

Monitor Potassium, Calcium, Magnesium, Phosphate.

·       Corticosteroids can be used at a dosage of 1-2mg/kg/day (PREDNISOLONE); effective only in sarcoidosis, melanoma, lymphoma, leukemia, Vitamin D intoxication (not useful in solid tumors). Desirable effect has a latency of 2-3 weeks to appear. Mechanism of action is by decreasing bone resorption and intestinal absorption of Vitamin D. IV 100-500mg of Hydrocortisone can be used for resistant hypercalcemias.

·       Mithramycin 25 mcg/kg over 4-8h. as a SD. If hypercalcemia persists for24-48h after that, repeat the dose daily for 2-4 days. If necessary thereafter wkly.

·       Calcitonin 100-200 U IV/IM, reduces calcium within 2-4h; short lived action, can be prolonged by addition of corticosteroids. Subcutaneous 4 U/kg q 12hly can be given.

·       Bisphosphonates induce a slower but more sustained and complete response. IVPamidronate (upto 90mg), Etidronate (500mg) can be given.

·       Phosphate infusions no longer recommended because of vessel wall and metastaticcalcification.