Ca+2 Mg+2

PO4-2

and Cl-

• Most of the calcium in the body is stored in the bones as hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂).

• Calcium in the plasma : 45% free ionized form

45% bound to proteins (predominantly albumin) 10% complexed with anions (eg: citrate ,sulfate,phosphate)

Normal serum Ca+29-11mg/dl.

Physiologically active

Typically measured in routine

blood tests

In addition to its regulation by serum Ca+2,PTH is also regulated by serum acid –base status.

↓SERUM pH ↑PTH

↑urinary excretion of Phosphate

↑buffering of H+ions excreted

in the distal tubule

↑serum pH

Hypercalcemia

PTH excessHormone Independent Bone Resorption

Vitamin D excess

Excessive Dietary intake of Ca+2

Thiazides

Rare Miscellaneous Mechanisms

Hyperparathyroidism

Osteolytic bone metastases

↑intake of Vitamin D

Milk-Alkali Syndrome(↑intake of CaCO3)

Adrenal Crisis

PTHrP –secreting malignancy

Paget’s disease

Ectopic Calcitriol Production

Severe Rhabdo. Complicated by AKI

Lithium Hyperthyroidism

Theophylline Toxicity

Familial Hypocalciuric hypercalcemia

Immobilization

Clinical manifestations

• Stones , bones,groans and psychiatric overtones (moans).

• Other symptoms include : Constipation Anorexia Nausea Weakness lethargy There are no reliable physical findings of

hypercalcemia.

• Short QT interval • Additional findings are: Dehydration Renal Insufficiency Nephrogenic Diabetes insipidus Type 1 Renal tubular acidosis

Diagnostic Evaluation

• Step1: correct calcium for low albumin

• Step2:Perform thorough Physical examination and obtain Chest X-ray.

• Step3 : Measure PTH.

Elevated calcidiol

Bone mets,rare

causes

Ectopic productio

n of Calcitriol

malignancyExcessive

dietary intake of

calcium or Vitamin D

None of 3 are

elevated

PTHrP elevated

Elevated calcitriol

with normal calcidiol10Hyperp

arathyroidism

High or High-normal

Low or low - normal

Hypocalcemia

etiology

•Hypoparathyroidism:• s/p thyroidectomy or other neck surgery• s/p I131 therapy for graves disease or thyroid cancer• Autoimmune hypoparathyroidism• Infiltration of parathyroids• Hypomagnesemia• Genetic /congenital

• Vitamin D deficiency• Low dietary intake of Ca+2• Miscellaneous Osteoblastic bone metastases

• Pancreatitis• Hungry bones syndrome•Multiple Transfusions• Acute Respiratory Alkalosis • Hyperphosphatemia• Bisphosphonates

Symptoms• Perioral paresthesias• Muscle stiffness ,spasms and cramps• Shortness of breath (diaphragmatic spasms)• Diaphoresis

• EKG finding –long QT interval• Other severe symptoms –seizures, hypotension,

emotional lability , psychosis.

Signs

• Chvostek’s sign:Facial spasm elicited by tapping on the ipsilateral facial nerve anterior to the ear.

• Trousseau’s sign- Carpopedal spasm induced by inflation of a BP cuff above SBP for 3 minutes.

Diagnostic evaluation

• Step1 :correct calcium for low albumin

• Step 2: Measure PTH , creatinine , phosphate , magnesium , calcidiol and calcitriol

Treatment

• Oral calcium(1500-2000mg elemental calcium daily in divided doses)

• IV calcium

• Vitamin D

• Magnesium

Should be reserved for the pts with severe symptoms-seizures ,tetany, prolonged QT ,abrupt decrease

<7.5mg/dl

Although common to give as a slow bolus(ie.

over 10-20 min)this improves calcium

levels only transiently.

Magnesium sulfate IV (1-2gm)with frequent monitoring

Pts with moderate def. – 600-800units/day

Pts with severe malabsorption- 10000-50000units/day.

Phosphate • Serum phosphate level Reference range in adults, 2.5-4.5 mg/dL • in children, 3-6 mg/dL• hemolysis or hyperlipidemia of the

serum sample may lead to falsely elevated phosphorus levels

• Most of the phosphate in the body is also stored in the bones as hydroxyapatite.

• Most of the remainder of the body’s phosphate is intracellular ,as component of phospholipids in cell membranes ,DNA,RNA and ATP and ADP.

• The small fraction of phosphate that is in the serum exists as circulating phospholipids and inorganic phosphate.

• Inorganic phosphate consists of HPO4-2 and

H2PO4-1 in a 4:1 ratio at pH 7.40 which is

physiologically active and what is typically measured in routine blood tests.

Hypophosphatemia

Etiology↓GI absorption:

↓Intake of dietary Phosphate(only seen in malnourished alcoholic)

Malabsorption Phosphate binders (eg. Calcium

acetate,Al+3 and Mg+2 containing antacids)

• ↑Urinary Excretion:•Vitamin D deficiency •Hyperparathyroidism•Variety of rare genetic disorder• Fanconi syndrome(proximal tubule

dysfunction

• Internal Redistribution:–Refeeding syndrome–Hungry bones syndrome–Acute respiratory alkalosis

MECHANISM

EARLY MANIFESTATIONS

(serum phosphate 1-2 mg/dl)

LATE MANIFESTATIONS(serum phosphate <1mg/dl)

Dysfunctional bone metabolism

↓bone mineralization

Bone pain

Rickets(children)Osteomalacia

(adults)

↓Intracellular

ATP

↓Myocardial contractility

Proximal muscle weakness

↑RBC rigidityEncephalopathy

Heart failureRhabdomyolysis

Hemolysis Seizures , coma

↓RBC 2,3DPG

↑affinity of Hb for O2

Systemic ischemia

Diagnostic evaluation

• The first step is measurement of 24hr urine phosphate excretion , and/ or fractional excretion of phosphate.(FE PO4)

Patients with uncorrectable ,ongoing urinary loss of phosphate will require ongoing oral phosphate repletion

even after serum phosphate is normalized

Hyperphosphatemia

Hyperphosphatemia symptoms

• Altered mental status• Delirium• Obtundation• Coma• Convulsions and seizures• Muscle cramping or tetany• Neuromuscular hyperexcitability (ie, Chvostek and

Trousseau signs)• Paresthesias (particularly perioral and distal

extremities)

Diagnostic evaluation

• The cause of the clinically relevant hyperphosphatemia is rarely a diagnostic mystery.

• Pseudohyperphosphatemia should be identified

• When uncertain as to the etiology , it is best to start by working up the likely concurrent calcium disorder.

Acuity Renal function Treatment

Acute

intact

For mild hyperphosphatemia ,therapy is

unnecessaryWill usually resolve within 6-

12hrs.IF degree is Life threatening Consider normal saline +/-

acetazolamide

impairedConsider

Hemodialysis

Acuity Renal function Treatment

ChronicIntact

For Vitamin D excess and Hypoparathyroidism treatment

of the underlying condition is usually sufficient

For Familial tumoral calcinosis ,treatment requires

low phosphate diet and phosphate binders

impaired low phosphate diet and phosphate binders

Magnesium

• needed for more than 300 biochemical reactions in the body. It helps to maintain – normal nerve and muscle function– supports a healthy immune system,– keeps the heart beat steady, and helps bones

remain strong.– It also helps regulate blood glucose levels and– aid in the production of energy and protein.

• ~50% of Mg is stored in bone• ~49% is in the intracellular space

• Of the remaining 1%:• ~20%bound to albumin• ~10% complexed with anions• ~70% Unbound(ie. Biologically

active)

• Serum Mg correlates poorly with total body Mg content.

• Average daily intake: 360mg

Hypomagnesemia

Etiology

• ↓GI uptake:–Poor dietary intake(particularly

common in alcoholics)–Proton pump Inhibitors–Primary intestinal Hypomagnesemia–Excessive GI losses:–Chronic diarrhea

• Renal losses :• Medications:Loop and Thiazide diuretics

• Amphotericin B• Aminoglycosides

• Electrolyte abnormalitiesHypercalcemia

Hypokalemia• Transient renal tubular dysfunction• Familial Renal Mg wasting syndromes• Miscellaneous Pancreatitis

•Hungry bones syndrome

Symptoms/Signs :

– Tetany (seizures in children/neonates)– Hypokalemia– Hypoparathyroidism hypocalcemia (<1.2mg/dL)– Vitamin D deficiency (due to low calcitriol)– EKG changes: widened QRS, peaked T-waves, PR

interval prolongation, – Ventricular arrhythmias (especially during

ischemia or bypass), like TORSADE de POINTES.

Treatment• Abrupt increases in serum Mg (as seen during IV

administration )inhibit Mg reabsorption in the loop of henle and lead to transient Mg wasting ,limiting the utility of the IV route.

• In the absence of symptoms ,arrhythmias ,or concurrent hypokalemia oral repletion is usually preserved.

• Treat underlying disease (PPI, diuretics, alcohol, uncontrolled diabetes)

• In the presence of symptoms ,arrhythmias , and/or hypokalemia , IV Mg can be given ,usually 1-2gms at a time .

• Although it is common practice to give IV Mg relatively quickly (ie.,<15min/gram),this speed is usually not necessary.

• Avoid replacement in patients with reduced GFR

Hypermagnesemia

etiology• Renal failure

• Excessive Mg intake– Magnesium citrate– Overdose of Epsom salts

• Excessive IV Mg infusion (eg: ecclampsia)• Magnesium containing enemas

• Miscellaneous –Tumor lysis syndrome

Clinical manifestations

CardiovascularBradycardiaConduction

blockHypotension

NeuromuscularDecreased reflexesMuscle weaknessDrowsiness , comaParasympathetic

blockade-Cutaneous flushing

Dry mouthDilated pupils

Urinary retention

Chloride Cl-

• Chloride - the major anion of extracellular fluid

• Chloride accounts for two-thirds of all serum anions.

–Chloride moves passively with Na+ or against HCO3

- to maintain neutral electrical charge

–Chloride usually follows Na (if one is abnormal, so is the other)

Functions –- not completely known,–it maintains cellular integrity by:•hydration•osmotic pressure• electrical neutrality & other functions

• Chloride is secreted by the stomach's mucosa as hydrochloric acid.

• Normal range: 98-106 mmol/L

• Critical values: < 70 or >120 mmol/L

• Chloride daily requirements for adults are 80-120 mEq/d as NaCL

• CSF – 120-132 mEq/L

Hypochloremia

• Total body chloride depletion

Extrarenal:– Inadequate NaCl intake   –Vomiting   –Small bowel fistulas 

• Renal:• Diuretic abusers • Salt-losing nephropathy  • Interstitial nephritis  • Adrenal insufficiency

• Dilutional :(decreased chloride concentration)• Increased effective circulatory blood

volume •Hypertonic infusions  • Pathologic water drinkers • Intrinsic renal diseases

Symptoms

• Excess fluid loss or dehydration (diarrhea, vomiting)

• Muscle hypertonicity (Spasticity)• Tetany• Shallow, depressed breathing• Muscle weakness• Sweating• High fever• Weight loss

diagnosis• Serum chloride levels < 98 mEq/L confirm the diagnosis.• Serum pH is above 7.45• Serum carbon dioxide levels > 32 mEq/L.• Serum osmolarity < 280mOsm/L

• Arterial blood gas analysis for identifying any acid base imbalance.

• Sometimes, a chloride test can be done.This finds out how much chloride is excreted in the urine.

Treatment• Electrolyte replacement therapy• IV administration of normal (0.9 NaCl) or half

strength saline (0.45 NaCl).• Ammonium chloride (an acidifying agent) – This is

for treating the metabolic alkalosis. Dosage depends up on the serum chloride level and weight of the patient. This is contraindicated in cases of impaired renal or liver functions.

• Oral or intravenous KCl (10-40mEq PO). IV should not exceed 20 mEq/hr.

• Dietary modifications–Consume sodium and potassium rich

diet, as hypochloremia causes deficiency of these nutrients.

Hyperchloremia

Causes of hyperchloremia may include

• Loss of body fluids from prolonged vomiting, diarrhea, sweating or high fever (dehydration).

• High levels of blood sodium.• Kidney failure, or kidney disorders• Diabetes insipidus or diabetic coma• Drugs such as: androgens, corticosteroids,

estrogens, and certain diuretics.

Symptoms/signs

• Excess fluid loss or dehydration (diarrhea, vomiting)• High blood sugar• Kussmaul’s breathing (deep and rapid breathing)• Dyspnea• Intense thirst• Weakness• Tachypnea• Hypertension• Pitting edema• Diminished cognitive ability• Possible coma

Hyperchloremia Diagnosis

• Serum chloride levels > 106 mEq/L confirm the diagnosis.

• Serum pH is under 7.35

• Serum carbon dioxide levels < 22 mEq/L.

• Sometimes, a chloride test can be done .

Treatment• Sodium bicarbonate I.V infusion– This is to raise the bicarbonate level in blood and

for permitting renal excretion of chloride anion, as chloride and bicarbonate compete to combine with sodium.

• Lactated Ringer’s solution– This is administered in cases of hyperchloremia. In

liver, this gets converted to bicarbonate, thereby increasing the base bicarbonate for correcting the acidosis caused.

• Low sodium diet– The excess chloride ions may combine with sodium

to form hypernatremia.