Calcium Disorders Lecture Notes PDF

Calcium Disorders Dr. Mona Mohamed  Intoduction ❑Most calcium in the body is in the form of hydroxyapatite in bone (99%). ❑Small fraction of total body calcium is contained in the extracelluar fluid (ECF). Approximately 60% of calcium in the ECF is ultrafilterable and exi...

Calcium Disorders Dr. Mona Mohamed  Intoduction ❑Most calcium in the body is in the form of hydroxyapatite in bone (99%). ❑Small fraction of total body calcium is contained in the extracelluar fluid (ECF). Approximately 60% of calcium in the ECF is ultrafilterable and exists either free in solution as ionized calcium (50%) or complesed to anions such as citrate, phosphate, sulfate, and bicarbonate (10%). The remaining 40% is bound to proteins (primarily albumin).  Introduction Serum or plasma calcium concentration is measured as either total or ionized calcium. Total calcium concentration is measured with a colorimetric assay and includes ionized, complexed, and bound calcium. Ionized calcium concentration is measured with a calcium-specific electrode and represents physiologically regulated calcium.  Introduction Both total and ionized calcium can be expressed in conventional units of mg per dl or mEq per L or in International System (SI) of units of mmol perL SI units (mmol per L) can be converted to mg per dl by multiplying by 4.  Summary 99% of total body calcium is stored in bone. Extracellular calcium accounts for a small fraction: of this, 50% is bound to albumin, with 40% available as physiologically active, free (or ionized) calcium.  Summary Total plasma calcium is composed of three components: Ionized calcium (50%). Complexed calcium (10%). Protein bound calcium (40%).  Why calcium is important? Calcium is important in skeletal health, membrane function, cell signalling, neuromuscular integrity and coagulation. The serum normal range is 2.1-2.5 mmol/L (1.2 mmol/L ionized), with calcium available from both the gut and bone stores.  Calcium Regulation Plasma-ionized calcium is regulated through a complex and coordinated interplay of parathyroid hormone (PTH) and 1,25 (OH)2 vitamin D3 (calcitriol) in the intestine, bone, and kidney.  Calcium regulation The parathyroid gland senses ESF-ionized calcium concentration through a calcium- sensing receptor. The parathyroid gland responds quickly (within minutes) to alterations in ionized calcium concentration.  Calcium regulation High concentrations of ESF calcium stimulate the receptor and activate second messenger pathways that, in, inhibit PTH release. Low ECF calcium concentration stimulates PTH secretion and production and increases parathyroid gland mass.  Calcium regulation An inverse sigmoid relationship exists between ECF calcium concentration and PTH secretion.  Calcium regulation In bone, PTH in the presence of permissive amounts of calcitriol stimulates reabsorption by increasing osteoclastic number and activity. In intestine, PTH enhances calcium and phosphate absorption indirectly by promoting the formation of cacitriol. In kidney, PTH augments distal tubular calcium reabsorption, stimulates calcitriol formation in the proximal tubule, and decreases proximal tubular phosphate and bicarbonate reabsorption.  Calcium regulation Calcitriol is produced in the proximal tubule through 1 alpha-hydroxylation of 25 (OH) vitamin D3 (calcidiol). The principal stimulators of 1 alpha- hydroxylase are PTH and hypophosphatemia.  Calcium regulation The major function of calcitriol is to enhance calcium and phosphate availability for new bone formation and prevention of symptomatic hypocalcemia and hypophosphatemia. In intestine and kidney, calcitriol increases production of calcium-binding proteins (calbindins) that aid in transcellular calcium movement. In bone, calcitriol potentiates PTH actions, stimulates osteoclastic reabsorption, and induces differentiation of monocytes into osteoclasts.  Calcium regulation Gut calcium absorption is controlled by calcitriol (active form of vitamin D). The ionized fraction is freely filtered, and mainly re-absorbed in the PCT and loop of Henle.  Calcium regulation Falling calcium activates parathyroid calcium- sensing receptors, leading to parathyroid hormone (PTH) release. PTH increases renal tubular calcium reabsorption and hydroxylation of vitamin D3 to the active metabolite, increasing intestinal uptake. PTH also enhances bone osteoclastic activity.  Hypercalcemia Etiology : Three basic pathophysiologic mechanisms contribute to hypercalcemia: Increased calcium absorption from the gastrointestinal tract. Decreased renal calcium excretion. Increased bone calcium resorption.  Increased calcium absorption from gastrointestinal tract Milk-alkali syndrome. Hypercalcemia in chronic kidney disease (CKD). Vitamin D intoxication. Granulomatous disorders.  Milk-alkali syndrome It is the result of ingestion of excess calcium and alkali.  Milk-alkali syndrome In the past, peptic ulcer disease was treated with milk and sodium bicarbonate. This calcium and alkali source used to be the most common cause of the milk-alkali syndrome. This regimen was replaced with histamine antagonists and proton pump inhibitors so that milk and sodium bicarbonate are now rare causes of this syndrome.  Milk-alkali syndrome Currently, this syndrome most often occurs in elderly women consuming excess calcium carbonate or calcium citrate for the treatment of osteoporosis. As a result, may now refer to this as the calcium-alkali syndrome rather than the milk- alkali syndrome.  Milk-alkali syndrome Alkalosis decreases renal calcium excretion and the resultant hypercalcemia, nephrocalcinosis, and subsequent renal dysfunction prevent correction of the alkalosis. Many of these patients are also receiving vitamin D supplements that increase intestinal calcium absorption.  Milk-alkali syndrome ❑ Patients present with the classic triad of : Hypercalcemia. Metabolic alkalosis. Elevated serum creatinine concentration.  Hypercalcemia in CKD Hypercalcemia in CKD is uncommon, except in patients treated with calcium and vitamin D supplements. This disorder and milk-alkali syndrome illustrate the important concept that hypercalcemia from excessive dietary calcium ingestion alone does not occur in the absence of renal impairment.  Vitamin D intoxication Vitamin D intoxication also results in hypercalcemia. Calcium is absorbed primarily in the small intestine, and this process is stimulated by calcitriol.  Granulomatous disorders Hypercalcemia may also be secondary to granulomatous disorders such as sarcoidosis, how? Activated macrophages produce calcitriol, which leads to increased intestinal absorption of dietary calcium.  Causes of increased calcium resorption from bone: Hyperparathyroidism. Malignancy. Hyperthyroidism. Immobilization. Paget’s disease. Drugs e.g. thiazide diuretics. Signs and symptoms of hypercalcemia Signs and symptoms of hypercalcemia are related to the severity and rate of rise in the plasma-ionized calcium concentration. Mild hypercalcemia is generally asymptomatic and often discovered on routine blood chemistries. In contrast, severe hypercalcemia is often associated with polyuria, polydepsia, neurological and gastrointestinal symptoms.  Neurological symptoms of hypercalcemia The patient may present with a wide range of central nervous system symptoms, from mild mental status changes to depression, confusion, and coma. Gastrointestinal symptoms include: Constipation. Anorexia. Nausea. Vomiting. Abdominal pain may result from hypercalcemia-induced peptic ulcer disease or pancreatitis.  Hypocalcaemia Causes of hypocalcaemia: Vitamin D deficiency. - Malnutrition. - Malabsorption. - Chronic renal failure (CRF). - Vitamin D-depentent rickets. Hypoparathyroidism. Hyperphosphataemia. Acute pancreatitis. Hypomagnesemia.  Symptoms & signs of hypocalcaemia Depression and mental status changes.. Anxiety and irritability. Peri-oral (circumoral) and distal extremity paraesthesia. Carpo-pedal spasm. Tetany. Convulsions. Arrythmias.  Symptoms & signs of hypocalcaemia Examine for Chvostek’s sign and Trousseau’s sign. If chronic, cataract, dental changes, bone pain and muscle weakness with or without skeletal deformities.  Trousseau’s sign It is the development of wrist flexion, metacarpophalangeal joint flexion, hyperextended fingers, and thumb flexion a sphygmomanometer cuff is inflated around the arm to 20 mmHg above systolic pressure for 3 minutes. i.e occlude brachial artery with BP cuff inflated above SPB, observe wrist and finger flexion.  Chvostek’s sign It is a facial twitch elicited by tapping on the facial nerve just below the zygomatic arch with the mouth slightly open. i.e. tap over the parotid for facial muscle twitching as Cr. VII excited