HYPOCALCEMIC TETANY

by G.NAGARJUNA GOUD

CALCIUM O

BJEC

TIVE

S Sources and RDA

Metabolism of calcium

Functions of calcium

Regulation of plasma calcium

Disorders of calcium metabolism

CALCIUM

Calcium is the most abundant mineral in the body

Human body contain about 1-1.5 kg of calcium

SOURCES OF CALCIUM

DAILY REQUIREMENTS OF CALCIUM

Children 1000mg/day

Adults 500mg/day

Pregnancy and lactation1500mg/day

METABOLISM OF CALCIUM

Absorption Factors

affecting absorption

Mechanism of absorption

Excretion of calcium

Distribution and storage

METABOLISM OF CALCIUM - ABSORPTION

Site

Efficiency

Upper small

intestine

20-30% of dietary Ca

FACTORS AFFECTING CALCIUM ABSORPTION

Calcium absorption is increased by

CalcitriolPTHHigh protein dietOptimum Ca:P ratioAcidic pHBile salts

Absorption is decreased by

Alkaline pHPhytates and oxalatesSteatorrheaVitamin D deficiencyExcess phosphate in diet

MECHANISM OF CALCIUM

ABSORPTIONCalcium

absorption occurs by 1,25(OH)2D3

mediated mechanism.

EXCRETION OF CALCIUM

Stools

Unabsorbed calcium in

the diet60 – 70%

Urine

50-200mg/day

Sweat

15mg/day

DISTRIBUTION AND STORAGE OF CALCIUM

Human body contain

about 1-1.5 kg of calcium

99% present in bone and teeth

1% in soft tissue and extracellular fluid

Plasma calcium : 9-11mg/100mlIonized calcium: 4.65-5.25mg/100ml

FUNCTIONS OF CALCIUM

Formation of bone and teeth

Nerve conduction

Muscle contraction

Activation of enzymes

Blood coagulation Secretion of hormones

As a second messenger

Action on myocardium

REGULATION OF ENZYME ACTIVITY

Ca++ activates • Glycogen

phosphorylase kinase

• Amylase • PDH, IDH and α-

KGDH

Ca++ Inhibits • Pyruvate kinase• Trypsin

REGULATION OF PLASMA CALCIUM

50%40%

10%

%

Free or ionized calcium

Protein bound(mainly albumin) 40

complex with anions-citrates,bicarbonates,lactates,phosphates

REGULATION OF PLASMA CALCIUM

3 Organs

Gut

Bone

Kidney

3 Hormones

Calcitriol

PTH

Calcitonin

DISORDERS OF CALCIUM METABOLISM

HypocalcemiaHypercalcemia

HYPOCALCEMIA

Causes Features Treatment

HYPOCALCEMIA CAUSES Inadequate intake

Impaired absorption

Increased excretion

Magnesium deficiency

Acute pancreatitis

Causes of hypocalcemiaCauses of hypocalcemiaI. Factitious hypocalcemia:

Is the reduction of the total , not the ionized fraction of serum calcium with reduction of serum albumin, the patient don't have any symptoms or signs of hypocalcaemia If the serum albumin levels fall to < 4 g/dl., the usual correction is to add 0.8 mg/dl to the measured total serum calcium for every 1.0 gm/dl reduction of serum albumin.

II. Hypoparathyroidism

Hypoparathyroidism is the state of decreased secretion or decreased activity of PTH

Manifestations that occur result from associated hypocalcemia and hyperphosphatemia.

Three categories of hypoparathyroidismThree categories of hypoparathyroidism

Deficient PTH secretion(> 99% of all cases

Deficient PTH secretion(> 99% of all cases

In ability to make an active form of PTH care.

In ability to make an active form of PTH care.

Inability of kidneys and bones to respond to parathyroid hormone being produced by normal parathyroid .

Inability of kidneys and bones to respond to parathyroid hormone being produced by normal parathyroid .

III. Magnesium depletion and hypocalcemia: Normal mg serum level is 1.6-2.1 mEq/L Mg metabolism has a close association with

that of calcium: Are competitive for renal tubular reabsorption Are physiological antagonists in CNS Mg is necessary for PTH release and for its action

Patients with hypocalcemia due to Mg deficiency should be treated with IV mg at a dose of 48 mEq over 24 hours.

IV. Hypocalcemia and hyper phosphatemia: 85% is free and only 15% is protein bound Hypocalcemia and tetany may occur if

serum phosphorus rises rapidly Hyperphosphatemia alters calcium and

phosphate ion solubility products, and calcium deposition in soft tissue may occur.

V. Medications and toxins causing hypocalcemia:

Mithramycin, bisphosphonates, calcitionin, oral or parentral phosphate preparation, anticonvulsants manly (phenytoin or phenobarbital)

Plasmapheresis with citrated blood Radiographic contrast dyes Chemotherapeutic agents. During surgical procedures, hypocalcemia may

occur in the absence of citrated bl. Infusion, may be due to acute hemodilution by physiological saline.

VI.Hungry Bone syndrome

VII.Hypocalcemia and pancreatitis

VIII. Hypocalcemia associated with critical

illness.

IX.Vitamin D disorders resulting in hypocalcemia:

Both inherited and aquired disorders of vit D and its metabolites may be associated with hypocalcemic disorder.

Decreased synthesis of vit D3 in the skin may be due to lack of sun exposure

Fat malabsorption Extensive liver disease Drugs, mainly anticonvulsant. Nephrotic syndrome, may be due to excretion of vit D

binding protein. Ch. R.F. with reduction of GFR to <30% may present

with production of 1-25 dihydroxy vit D.

Hypocalcemia - Features Muscle cramps

and tetany

Laryngospasm

Convulsion

Cardiac arrhythmias

Prolongation of QT interval

Cataract

Chronic hypocalcemia

HYPOCALCEMIA – SIGNS OF TETANY

Contraction of facial muscle in response to tapping the facial nerve, (insensitive test)

Chvostek’s sign

Carpal spasm occurring after occlusion of the brachial artery with BP cuff with pressure 20 mm of Hg above systolic BP for 3-5min.

Trousseau’s sign

Differential diagnosis• Hyperventilation syndrome in hystericals due

to respiratory alkalosis. Rx- simple mask with rebreathing exercises and tranquilisers.

Management1. Dependent on the underlying cause and severity2. Administration of calcium alone is only transiently

effective3. Mild asymptomatic cases: Often adequate to

increase dietary calcium by 1000 mg/day4. Symptomatic: Treat immediately

Investigations• Serum calcium • Ionic calcium• Serum magnesium• Blood urea• Serum creatinine• Serum amylase & serum lipase• Serum proteins;- total proteins,albumin,globulin• Serum electrolytes• PTH hormone immunoassay.• Tests for vitamin D metabolites.• Measurements of the urinary cyclic AMP response to exogenous PTH.• 25(OH)D assays.

HYPOCALCEMIA - TREATMENTSevere symptomatic

cases

Intravenous Calcium gluconate

Asymptomatic cases

Calcium carbonate

Vitamin D

Rx for factitious hypocalcemia• Low serum albumin levels can cause a reduction in

the total, but not the ionized ,fraction of serum calcium.

• Each 1g/dL reduction in the serum albumin concentration will lower the total calcium concentration by approximately 0.8mg/dL without affecting the ionized calcium concentration.

-:Formula:-• Thus ,calcium level should be corrected in patients with low

serum albumin levels ,using the formula :• Corrected calcium(mg/dL)= measured total

Ca(mg/dL)+0.8(4.0-serum albumin <g/dL>),• Where 4 respresents the average albumin

level.

i. Acute hypocalcaemia:

Calcium gluconate is the preferred IV calcium.Calcium gluconate contains 90 mg of elemental calcium/ 10 ml ampoule.Usually 1-2 ampoule (180 mg of elemental calcium) diluted in 50-100 ml of 5% dextrose, is infused over 10 minutes. This can be repeated until the patient's symptoms have cleared. The goals should be to raise serum calcium by 2-3 mg/dl with the administration of 15mg/kg of elemental calcium over 4-6 hours.Calcium should be maintained in the low normal range. If possible oral calcium supplementation should be initiated together with vit D.

ii- Chronic hypocalcemia• Patients who are asymptomatic or with mild

symptomatic hypocalcaemia can be treated with oral calcium and vit D.

• The overall goal of therapy is to maintain serum calcium in the low normal, range, serum calcium should be tested every 3-6 months.

Hypocalcemia with concurrent hypomagnesemia

• Often cannot correct the Ca unless the Mg is corrected• Give 2 gm of Mg (16 meq) of MgSO4 as a 10% solution over

10 to 20 minutes• Followed by 1 gm MgSO4 (8 meq) at 100 mL/hr• Continue intravenous MgSO4 as long as Mg < 1 mg/dL• Careful monitoring if patient has impaired renal function

Calcium saltsDrug preparation: Ca= elemental calcium• Calcium chloride (27.2% cal) 10% solution

(100 mg/ml) given IV but cause local irritation.• Calcium gluconate.• Calcium carbonate: 40% calcium e.g oscal,

titralac.• Calcium citrate 21% cal (citracal).• Calcium lacate 13% calcium.

Vit D preparation: Ergocalciferol: (calciferol) Calcifediol (25-hydoxy vit. ) Calcitriol: (1,25 dihydroxy vit D )

Vitamin D dosage in Rx of chronic hypocalcemia

Simple dietary deficiency - can be corrected by the use of ergocalciferol 400-2000 IU/day

• However in conjunction with other hypocalcemic disorders (e.g., underlying impairments in vitamin D metabolism or renal insufficiency) larger doses may be needed e.g., a 6 to 8 week regimen of 50,000 units, dosed weekly

• Severe malnutrition or malabsorption – may require even higher doses