Electrolyte imbalances

Hyponatremia

• ECV (extracellular fluid) is hypo-osmolar compared to ICV (intracellular fluid), causing water to move into the ICV.
• The brain is confined within a fixed cranium, making cerebral edema the most significant effect of hyponatremia.
• Limited diffusion of solutes across the BBB (blood-brain barrier) prevents equilibration of solutes among fluid compartments.

Initial Treatment of Hyponatremia

• Initial treatment involves fluid restriction, diuresis, and potential use of vasopressin receptor antagonists (such as tolvaptan and conivaptan).

Correction of Hyponatremia

• Rapid correction of hyponatremia can cause neurologic complications, including central pontine myelinolysis.
• Correction should be limited to 1-2 mEq/L/hr using 3% saline at 1-2 mL/kg/hr.
• The sodium level should not be raised more than 10-15 mmol/L in 24 hours.

Hyponatremia

• ECV (extracellular fluid) is hypo-osmolar compared to ICV (intracellular fluid), causing water to move into the ICV, leading to cerebral edema.
• The brain's fixed cranium and limited diffusion of solutes across the BBB (blood-brain barrier) prevent equilibration of solutes among fluid compartments, exacerbating cerebral edema.

Treatment of Hyponatremia

• Initial treatment involves fluid restriction, diuresis, and potential use of vasopressin receptor antagonists (e.g., tolvaptan and conivaptan).
• Rapid correction of hyponatremia should be avoided to prevent neurologic complications, including central pontine myelinolysis.
• Correction should not exceed 1-2 mEq/L/hr with 3% saline at 1-2 mL/kg/hr, and not raised more than 10-15 mmol/L in 24 hours.

Sodium Levels and Physiologic Manifestations

• 135-130 mEq/L: Little to no symptoms, with possible mild neurologic signs.
• 129-125 mEq/L: Nausea and malaise.
• 124-115 mEq/L: Headache, lethargy, and altered level of consciousness (LOC).

Hyponatremia

• ECV is hypo-osmolar compared to ICV, causing water to move into ICV
• Most significant effect is cerebral edema due to the brain being confined within the fixed cranium
• Limited diffusion of solutes across the BBB prevents equilibration of solutes among fluid compartments

Treatment of Hyponatremia

• Initial treatment involves fluid restriction, diuresis, and potential use of vasopressin receptor antagonists (tolvaptan and conivaptan)
• Rapid correction of hyponatremia can cause neurologic complications including central pontine myelinolysis
• Correction rate: no more than 1-2 mEq/L/hr with 3% saline at 1-2 mL/kg/hr, not raised more than 10-15 mmol/L in 24 hours

Sodium Levels and Physiologic Manifestations

• 135-130 mmol/L: little to no symptoms, may see mild neurologic signs
• 129-125 mmol/L: nausea, malaise
• 124-115 mmol/L: headache, lethargy, altered level of consciousness

Hyponatremia

• ECV is hypo-osmolar compared to ICV, causing water to move into ICV
• Most significant effect is cerebral edema due to the brain being confined within the fixed cranium
• Limited diffusion of solutes across the BBB prevents equilibration of solutes among fluid compartments

Treatment of Hyponatremia

• Initial treatment involves fluid restriction, diuresis, and potential use of vasopressin receptor antagonists (tolvaptan and conivaptan)
• Rapid correction of hyponatremia can cause neurologic complications including central pontine myelinolysis
• Correction rate: no more than 1-2 mEq/L/hr with 3% saline at 1-2 mL/kg/hr, not raised more than 10-15 mmol/L in 24 hours

Sodium Levels and Physiologic Manifestations

• 135-130 mmol/L: little to no symptoms, may see mild neurologic signs
• 129-125 mmol/L: nausea, malaise
• 124-115 mmol/L: headache, lethargy, altered level of consciousness

Classification of Hyponatremia

• Isotonic Hyponatremia (Pseudohyponatremia) is characterized by a serum osmolality of 270-300.
• Causes of Isotonic Hyponatremia include: • Hyperlipidemia • Hyperproteinemia • Multiple myeloma • Excess isotonic nonelectrolyte solutions

Hypertonic Hyponatremia

• Hypertonic Hyponatremia is characterized by a serum osmolality greater than 300.
• Causes of Hypertonic Hyponatremia include: • Hyperglycemia • Mannitol excess • Glycerol therapy

Hypotonic Hyponatremia

• Hypotonic Hyponatremia is characterized by a serum osmolality less than 270.

Classification of Hyponatremia

• Isotonic Hyponatremia (Pseudohyponatremia) is characterized by a serum osmolality of 270-300.
• Causes of Isotonic Hyponatremia include: • Hyperlipidemia • Hyperproteinemia • Multiple myeloma • Excess isotonic nonelectrolyte solutions

Hypertonic Hyponatremia

• Hypertonic Hyponatremia is characterized by a serum osmolality greater than 300.
• Causes of Hypertonic Hyponatremia include: • Hyperglycemia • Mannitol excess • Glycerol therapy

Hypotonic Hyponatremia

• Hypotonic Hyponatremia is characterized by a serum osmolality less than 270.

Hyponatremia

• ECV (extracellular fluid) is hypo-osmolar compared to ICV (intracellular fluid), causing water to move into the ICV.
• The most significant effect of hyponatremia is cerebral edema, which occurs because the brain is confined within the fixed cranium.
• Limited diffusion of solutes across the BBB (blood-brain barrier) prevents equilibration of solutes among fluid compartments.

Treatment of Hyponatremia

• Initial treatment involves fluid restriction, diuresis, and potential use of vasopressin receptor antagonists (tolvaptan and conivaptan).
• Rapid correction of hyponatremia can cause neurologic complications, including central pontine myelinolysis.
• Correction of hyponatremia should be limited to 1-2 mEq/L/hr with 3% saline at 1-2 mL/kg/hr, and not raised more than 10-15 mmol/L in 24 hours.

Sodium Levels and Physiologic Manifestations

• 135-130 mEq/L: Little to no symptoms, may see mild neurologic signs.
• 129-125 mEq/L: Nausea, malaise.
• 124-115 mEq/L: Headache, lethargy, altered LOC.

Classification of Hyponatremia

• Isotonic Hyponatremia (Pseudohyponatremia): Serum osmolality 270-300 mEq/L, caused by hyperlipidemia, hyperproteinemia, multiple myeloma, or excess isotonic nonelectrolyte solutions.
• Hypertonic Hyponatremia: Serum osmolality >300 mEq/L, caused by hyperglycemia, mannitol, or excess glycerol therapy.
• Hypotonic Hyponatremia: Serum osmolality <270 mEq/L.

Hyponatremia

• ECV is hypo-osmolar compared to ICV, so water moves into ICV, causing cerebral edema due to the confined space of the cranium.
• Limited diffusion of solutes across the BBB prevents equilibration of solutes among fluid compartments.

Treatment of Hyponatremia

• Initial treatment involves fluid restriction, diuresis, and potential use of vasopressin receptor antagonists (tolvaptan and conivaptan).
• Rapid correction of hyponatremia can cause neurologic complications, including central pontine myelinolysis.
• Correction should be no more than 1-2 mEq/L/hr with 3% saline at 1-2 mL/kg/hr, and not raised more than 10-15 mmol/L in 24 hours.

Sodium Levels and Physiologic Manifestations

• 135-130 mEq/L: Little to no symptoms, may see mild neurologic signs.
• 129-125 mEq/L: Nausea, malaise.
• 124-115 mEq/L: Headache, lethargy, altered level of consciousness.

Classification of Hyponatremia

• Isotonic Hyponatremia (Pseudohyponatremia): Serum osmolality 270-300, caused by hyperlipidemia, hyperproteinemia, multiple myeloma, and excess isotonic nonelectrolyte solutions.
• Hypertonic Hyponatremia: Serum osmolality >300, caused by hyperglycemia, mannitol excess, and glycerol therapy.
• Hypotonic Hyponatremia: Serum osmolality <270, caused by excessive water intake, heart failure, liver failure, and nephrotic syndrome.

Free Water Deficit Calculation

• Free water deficit can be calculated using the formula: [(Na/140)-1]xTBW

Classification of Hypernatremia

• Hypernatremia can be classified into three types based on total body water and sodium levels

Hypernatremia with Dehydration and Low Total Body Sodium

• Characterized by low total body water and low total body sodium
• Causes include:
  • Vomiting
  • Diarrhea
  • Continuous gastrointestinal suctioning
  • Osmotic diuresis

Hypernatremia with Low Total Body Water and Normal Total Body Sodium

• Characterized by low total body water and normal total body sodium
• Causes include:
  • Diabetes
  • Neurogenic disorders
  • Renal disease
  • Sickle cell disease
  • Aminoglycosides

Hypernatremia with Increased Total Body Sodium

• Characterized by high total body sodium
• Causes include:
  • Hypertonic saline infusion
  • Cushing syndrome
  • Conn syndrome
  • Hemodialysis

Clinical Signs of Hypernatremia with Increased Serum Osmolality

• At a serum osmolality of 350-375, symptoms include confusion, restlessness, agitation, and headache
• At a serum osmolality of 376-400, symptoms escalate to ataxia, tremors, and weakness
• At a serum osmolality of 401-430, symptoms further progress to hyperreflexia, muscle twitching, and muscle spasm
• At a serum osmolality above 430, severe and life-threatening symptoms occur, including coma, seizures, and ultimately, death

Clinical Signs of Hypernatremia with Increased Serum Osmolality

• At a serum osmolality of 350-375, symptoms include confusion, restlessness, agitation, and headache
• At a serum osmolality of 376-400, symptoms escalate to ataxia, tremors, and weakness
• At a serum osmolality of 401-430, symptoms further progress to hyperreflexia, muscle twitching, and muscle spasm
• At a serum osmolality above 430, severe and life-threatening symptoms occur, including coma, seizures, and ultimately, death

Hyponatremia

• Hyponatremia occurs when the ECV is hypo-osmolar compared to the ICV, causing water to move into the ICV.
• This leads to cerebral edema, as the brain is confined within the fixed cranium, and limited diffusion of solutes across the BBB prevents equilibration of solutes among fluid compartments.

Initial Treatment of Hyponatremia

• Initial treatment involves fluid restriction, diuresis, and potential use of vasopressin receptor antagonists (tolvaptan and conivaptan).
• Rapid correction of hyponatremia can cause neurologic complications, including central pontine myelinolysis.
• Correction should be done at a rate of 1-2 mEq/L/hr with 3% saline at 1-2 mL/kg/hr, and not raised more than 10-15 mmol/L in 24 hours.

Sodium Levels and Physiologic Manifestations

• Sodium levels of 135-130 mmol/L: little to no symptoms, may see mild neurologic signs.
• Sodium levels of 129-125 mmol/L: nausea, malaise.
• Sodium levels of 124-115 mmol/L: headache, lethargy, altered LOC.

Classification of Hyponatremia

• Isotonic Hyponatremia (Pseudohyponatremia): serum osmolality 270-300 mmol/L, caused by hyperlipidemia, hyperproteinemia, multiple myeloma, and excess isotonic nonelectrolyte solutions.
• Hypertonic Hyponatremia: serum osmolality >300 mmol/L, caused by hyperglycemia, mannitol excess, and glycerol therapy.
• Hypotonic Hyponatremia: serum osmolality <270 mmol/L, calculated using the formula: free water deficit = [(Na/140)-1]xTBW.

Hypernatremia

• Hypernatremia can be classified into three types:
  • Hypernatremia with dehydration and low total body sodium, caused by vomiting, diarrhea, continuous gastrointestinal suctioning, and osmotic diuresis.
  • Hypernatremia with low total body water and normal total body sodium, caused by diabetes, neurogenic, renal disease, sickle cell disease, and aminoglycosides.
  • Hypernatremia with increased total body sodium, caused by hypertonic saline infusion, Cushing syndrome, Conn syndrome, and hemodialysis.

Clinical Signs of Hypernatremia

• Serum osmolality of 350-375 mmol/L: confusion, restlessness, agitation, and headache.
• Serum osmolality of 376-400 mmol/L: ataxia, tremors, and weakness.
• Serum osmolality of 401-430 mmol/L: hyperreflexia, muscle twitching/spasm.
• Serum osmolality >430 mmol/L: coma, seizures, and death.

Hyponatremia

• Hyponatremia occurs when ECV is hypo-osmolar compared to ICV, causing water to move into the ICV and resulting in cerebral edema.
• Cerebral edema is the most significant effect due to the brain being confined within the fixed cranium.
• Limited diffusion of solutes across the BBB prevents equilibration of solutes among fluid compartments.

Treatment of Hyponatremia

• Initial treatment involves fluid restriction, diuresis, and potential use of vasopressin receptor antagonists (tolvaptan and conivaptan).
• Rapid correction of hyponatremia can cause neurologic complications, including central pontine myelinolysis.
• Correction should be done at a rate of 1-2 mEq/L/hr with 3% saline at 1-2 mL/kg/hr, and not raised more than 10-15 mmol/L in 24 hours.

Sodium Levels and Physiologic Manifestations

• 135-130 mmol/L: Little to no symptoms, may see mild neurologic signs.
• 129-125 mmol/L: Nausea, malaise.
• 124-115 mmol/L: Headache, lethargy, altered LOC.

Classification of Hyponatremia

• Isotonic Hyponatremia (Pseudohyponatremia): Serum osmolality 270-300, caused by hyperlipidemia, hyperproteinemia, multiple myeloma, and excess isotonic nonelectrolyte solutions.
• Hypertonic Hyponatremia: Serum osmolality >300, caused by hyperglycemia, mannitol excess, and glycerol therapy.
• Hypotonic Hyponatremia: Serum osmolality <270, caused by free water deficit.

Hypernatremia

• Classification:
  • Hypernatremia with dehydration and low total body sodium, caused by vomiting, diarrhea, continuous gastrointestinal suctioning, and osmotic diuresis.
  • Hypernatremia with low total body water and normal total body sodium, caused by diabetes, neurogenic, renal disease, sickle cell disease, and aminoglycosides.
  • Hypernatremia with increased total body sodium, caused by hypertonic saline infusion, Cushing syndrome, Conn syndrome, and hemodialysis.

Clinical Signs of Hypernatremia

• 350-375 mmol/L: Confusion, restlessness, agitation, headache.
• 376-400 mmol/L: Ataxia, tremors, weakness.
• 401-430 mmol/L: Hyperreflexia, muscle twitching/spasm.
• >430 mmol/L: Coma, seizures, death.

Potassium Imbalance and Hyponatremia

• Patients with potassium levels >5.5 mmol/L or hyponatremia are at risk of complications.
• ECV (extracellular fluid) is hypo-osmolar compared to ICV (intracellular fluid), causing water to move into the ICV and leading to cerebral edema.
• The brain's confinement within the fixed cranium exacerbates the edema.
• Limited diffusion of solutes across the BBB (blood-brain barrier) prevents equilibration of solutes among fluid compartments.

Treatment of Hyponatremia

• Initial treatment involves fluid restriction, diuresis, and potential use of vasopressin receptor antagonists (tolvaptan and conivaptan).
• Rapid correction of hyponatremia can cause neurologic complications, including central pontine myelinolysis.
• Correction should be limited to 1-2 mEq/L/hr with 3% saline at 1-2 mL/kg/hr, and not raised more than 10-15 mmol/L in 24 hours.

Sodium Levels and Physiologic Manifestations

• Sodium levels between 135-130 mmol/L: little to no symptoms, with possible mild neurologic signs.
• Sodium levels between 129-125 mmol/L: nausea, malaise.
• Sodium levels between 124-115 mmol/L: headache, lethargy, altered level of consciousness.

Hyponatremia Classification

• Isotonic Hyponatremia (Pseudohyponatremia): serum osmolality 270-300 mmol/L, caused by hyperlipidemia, hyperproteinemia, multiple myeloma, or excess isotonic nonelectrolyte solutions.
• Hypertonic Hyponatremia: serum osmolality >300 mmol/L, caused by hyperglycemia, mannitol excess, or glycerol therapy.
• Hypotonic Hyponatremia: serum osmolality <270 mmol/L, caused by free water excess.

Hypernatremia Classification

• Hypernatremia with dehydration and low total body sodium: caused by vomiting, diarrhea, continuous gastrointestinal suctioning, or osmotic diuresis.
• Hypernatremia with low total body water and normal total body sodium: caused by diabetes, neurogenic, renal disease, sickle cell disease, or aminoglycosides.
• Hypernatremia with increased total body sodium: caused by hypertonic saline infusion, Cushing syndrome, Conn syndrome, or hemodialysis.

Clinical Signs of Hypernatremia

• Serum osmolality 350-375 mmol/L: confusion, restlessness, agitation, headache.
• Serum osmolality 376-400 mmol/L: ataxia, tremors, weakness.
• Serum osmolality 401-430 mmol/L: hyperreflexia, muscle twitching/spasm.
• Serum osmolality >430 mmol/L: coma, seizures, death.

Potassium Imbalance and Hyponatremia

• Hyponatremia occurs when serum sodium (Na) level is <135 mmol/L
• In hyponatremia, ECV is hypo-osmolar compared to ICV, causing water to move into the ICV
• Most significant effect is cerebral edema due to limited diffusion of solutes across the BBB
• Initial treatment involves fluid restriction, diuresis, and potential use of vasopressin receptor antagonists (tolvaptan and conivaptan)
• Rapid correction of hyponatremia can cause neurologic complications, including central pontine myelinolysis

Sodium Levels and Physiologic Manifestations

• 135-130 mmol/L: Little to no symptoms, may see mild neurologic signs
• 129-125 mmol/L: Nausea, malaise
• 124-115 mmol/L: Headache, lethargy, altered LOC

Hyponatremia Classification

• Isotonic Hyponatremia (Pseudohyponatremia): Serum osmolality 270-300, caused by hyperlipidemia, hyperproteinemia, multiple myeloma, or excess isotonic nonelectrolyte solutions
• Hypertonic Hyponatremia: Serum osmolality >300, caused by hyperglycemia, mannitol, or excess glycerol therapy
• Hypotonic Hyponatremia: Serum osmolality <270, caused by free water excess or deficient solute intake

Hypernatremia Classification

• Hypernatremia with dehydration and low total body sodium: caused by vomiting, diarrhea, continuous gastrointestinal suctioning, or osmotic diuresis
• Hypernatremia with low total body water and normal total body sodium: caused by diabetes, neurogenic, renal disease, sickle cell disease, or aminoglycosides
• Hypernatremia with increased total body sodium: caused by hypertonic saline infusion, Cushing syndrome, Conn syndrome, or hemodialysis

Clinical Signs of Hypernatremia

• 350-375 mmol/L: Confusion, restlessness, agitation, headache
• 376-400 mmol/L: Ataxia, tremors, weakness
• 401-430 mmol/L: Hyperreflexia, muscle twitching/spasm
• >430 mmol/L: Coma, seizures, death

Potassium Imbalance

• Patients with K > 5.5 are at risk of potassium imbalance
• Hypokalemia occurs when serum potassium levels are low

Hyponatremia

• Serum osmolality is hypo-osmolar compared to intracellular volume (ICV)
• Water moves into the ICV, causing cerebral edema due to the brain's fixed cranium
• Initial treatment involves fluid restriction, diuresis, and potential use of vasopressin receptor antagonists (tolvaptan and conivaptan)
• Rapid correction can cause neurologic complications, including central pontine myelinolysis
• Correction should be limited to 1-2 mEq/L/hr with 3% saline at 1-2 mL/kg/hr and not raised more than 10-15 mmol/L in 24 hours

Sodium Levels and Physiologic Manifestations

• 135-130: Little to no symptoms; may see mild neurologic signs
• 129-125: Nausea, malaise
• 124-115: Headache, lethargy, altered LOC

Classification of Hyponatremia

• Isotonic Hyponatremia (Pseudohyponatremia): Serum osmolality 270-300; associated with hyperlipidemia, hyperproteinemia, multiple myeloma, and excess isotonic nonelectrolyte solutions
• Hypertonic Hyponatremia: Serum osmolality > 300; associated with hyperglycemia, mannitol, and excess glycerol therapy
• Hypotonic Hyponatremia: Serum osmolality < 270; associated with free water deficit, calculated as [(Na/140)-1]xTBW

Hypernatremia

• Classification:
  • Hypernatremia with dehydration and low total body sodium; associated with vomiting, diarrhea, continuous gastrointestinal suctioning, and osmotic diuresis
  • Hypernatremia with low total body water and normal total body sodium; associated with diabetes, neurogenic disease, renal disease, sickle cell disease, and aminoglycosides
  • Hypernatremia with increased total body sodium; associated with hypertonic saline infusion, Cushing syndrome, Conn syndrome, and hemodialysis

Clinical Signs of Hypernatremia

• 350-375: Confusion, restlessness, agitation, and headache
• 376-400: Ataxia, tremors, and weakness
• 401-430: Hyperreflexia, muscle twitching/spasm
• >430: Coma, seizures, and death

Guidelines for Hyperkalemia Treatment

Clinical Features

• Electrocardiographic evidence of impending arrest (loss of P wave and QRS widening) requires immediate therapy
• Peaked T waves indicate potassium deficit and prompt therapy is necessary

Therapy

• IV infusion of calcium (10 mL of 10% calcium chloride over 10 min or 10 mL 10% calcium gluconate over 3-5 min) for membrane stabilization
• IV infusion of sodium bicarbonate (50-100 mEq over 10-20 min) to shift potassium intracellularly
• Glucose and insulin infusion (IV infusion of 50mL of D50W and 10 units of regular insulin, monitor glucose) to shift potassium intracellularly
• Immediate hemodialysis for 30 min to 4-6 hours to shift potassium intracellularly
• K-binding resins in GI tract to promote GI excretion
• Diuretic (furosemide 40mg IV) to promote renal potassium excretion

Onset and Duration of Action

• Calcium: 1-3 min onset, 30-60 min duration
• Sodium bicarbonate: 1-3 min onset, 30-60 min duration
• Glucose and insulin: 1-2 hours onset, 4-6 hours duration
• Hemodialysis: 30 min to 4-6 hours duration
• K-binding resins: 1-2 hours onset, 2-3 hours duration
• Diuretic: 15-30 min onset, 4-6 hours duration

Causes of Hyperkalemia

Increased K Intake/Absorption

• K supplements can cause hyperkalemia
• Salt substitutes can contribute to increased potassium intake
• Stored blood transfusions can lead to hyperkalemia
• Certain medications containing potassium can increase K levels

Impaired Renal Excretion

• Renal failure can cause hyperkalemia due to reduced K excretion
• Tubular defects can impair renal potassium excretion
• Nephropathy, obstructive uropathy, and nephritis can lead to hyperkalemia
• Pyelonephritis, a kidney infection, can cause hyperkalemia
• K-sparing diuretics can reduce potassium excretion
• Hypoaldosteronism, a condition characterized by low aldosterone levels, can cause hyperkalemia
• Systemic lupus erythematosus (SLE) can lead to hyperkalemia
• Addison's disease, a condition characterized by adrenal insufficiency, can cause hyperkalemia
• Adrenal hyperplasia, a condition characterized by adrenal gland overgrowth, can lead to hyperkalemia
• Certain drugs can impair renal potassium excretion

Transcellular Shift

• Acidosis, a condition characterized by high blood acidity, can cause potassium to shift out of cells
• Hypertonicity, a condition characterized by high blood osmolarity, can lead to potassium shift
• Insulin deficiency, common in diabetes, can cause potassium to shift out of cells
• Beta blockers, a type of medication, can cause potassium shift
• Digitalis, a medication used to treat heart conditions, can lead to potassium shift
• Succinylcholine, a medication used in anesthesia, can cause potassium shift
• Exercise, particularly strenuous exercise, can cause potassium shift
• Hyperkalemic periodic paralysis, a rare genetic disorder, can cause potassium shift

Cellular Injury

• Rhabdomyolysis, a condition characterized by muscle breakdown, can cause potassium release
• Severe intravascular hemolysis, a condition characterized by red blood cell destruction, can lead to potassium release
• Acute tumor lysis syndrome, a condition characterized by rapid tumor cell destruction, can cause potassium release
• Burns and crush injuries can cause potassium release from injured cells

Calcium Distribution

• 99% of calcium is stored in bones as hydroxyapatite, while 1% is found in plasma and cells.

Calcium Levels

• Total serum calcium levels range from 8.5-10.5 mg/dL.
• Serum levels are primarily maintained by Parathyroid hormone.

Calcium Forms

• Calcium is found in three forms:
• Ionized and physiologically active form (50%)
• Bound to anions (10%)
• Bound to proteins (40%)

Factors Affecting Calcium Levels

• Total amount of calcium is largely dependent on albumin concentration.
• Measuring ionized calcium is preferred, especially in patients with critical illness or hypoalbuminemia.

Effect of pH on Calcium

• Acidemia decreases protein-bound calcium and increases ionized calcium.
• Conversely, alkalosis increases protein-bound calcium and decreases ionized calcium.

Physiological Roles of Calcium

• Calcium acts as a second messenger in many cellular responses.
• It plays a role in:
  • Muscle contraction
  • Release of neurotransmitters and hormones
  • Blood coagulation
  • Myocardial contractility

Calcium Distribution

• 99% of calcium is stored in bones as hydroxyapatite, while 1% is found in plasma and cells.

Calcium Levels

• Total serum calcium levels range from 8.5-10.5 mg/dL.
• Serum levels are primarily maintained by Parathyroid hormone.

Calcium Forms

• Calcium is found in three forms:
• Ionized and physiologically active form (50%)
• Bound to anions (10%)
• Bound to proteins (40%)

Factors Affecting Calcium Levels

• Total amount of calcium is largely dependent on albumin concentration.
• Measuring ionized calcium is preferred, especially in patients with critical illness or hypoalbuminemia.

Effect of pH on Calcium

• Acidemia decreases protein-bound calcium and increases ionized calcium.
• Conversely, alkalosis increases protein-bound calcium and decreases ionized calcium.

Physiological Roles of Calcium

• Calcium acts as a second messenger in many cellular responses.
• It plays a role in:
  • Muscle contraction
  • Release of neurotransmitters and hormones
  • Blood coagulation
  • Myocardial contractility

Hyperkalemia

• Serum level > 5 mmol/L
• Occurs less frequently than hypokalemia
• At potassium levels > 8 mmol/L, ECG changes can lead to:
  • QRS widening
  • Sine waves
  • Ventricular fibrillation (V fib)
  • Cardiac arrest
• Treatment should rule out pseudohyperkalemia, a lab artifact caused by:
  • Hemolysis of the blood sample
  • Leukocytosis
  • Thrombocytosis
  • Prolonged clenching of the fist during blood draw
• Treatment goals:
  • Stabilize the cardiac membrane
  • Drive potassium from the extracellular compartment (ECV) to the intracellular compartment (ICV)
  • Remove potassium from the body

Causes of Hypocalcemia

Parathyroid Hormone Insufficiency

• Primary hypoparathyroidism can be caused by congenital syndromes or maternal hyperparathyroidism
• Secondary hypoparathyroidism can be caused by neck surgery, metastatic carcinoma, infiltrative disorders, or certain conditions such as hypo/hypermagnesemia, sepsis, pancreatitis, burns, or exposure to chemotherapy agents, ethanol, or cimetidine

Vitamin D Insufficiency

• Causes of vitamin D insufficiency include congenital rickets, malnutrition, malabsorption, liver disease, or renal disease (acute/chronic failure, nephrotic syndrome)
• Certain conditions can also contribute to vitamin D insufficiency, such as hypomagnesemia, sepsis, or taking anticonvulsants like phenytoin or primidone

PTH Resistance States

• Pseudohypoparathyroidism is a condition of PTH resistance

Calcium Chelation

• Calcium chelation can cause hypocalcemia due to hyperphosphatemia, citrate, free fatty acids, alkalosis, or fluoride poisoning

Neuromuscular Symptoms

• Paresthesia, muscle weakness, and muscle spasms occur due to hypocalcemia
• Tetany is a characteristic symptom of hypocalcemia
• Chvostek's sign is a facial or eye muscle twitching that indicates hypocalcemia
• Trousseau's sign is a carpopedal spasm that occurs in hypocalcemic patients
• Hyperreflexia is another notable symptom of hypocalcemia

Cardiovascular Symptoms

• Hypocalcemia can cause bradycardia (slow heart rate)
• Angina, hypotension, and congestive heart failure (CHF) are cardiovascular complications of hypocalcemia
• Cardiac arrest can occur in severe cases of hypocalcemia
• Hypocalcemia can lead to digitalis insensitivity, making digoxin therapy less effective
• QT prolongation is a cardiac symptom of hypocalcemia

Pulmonary Symptoms

• Bronchospasm and laryngospasm are respiratory complications of hypocalcemia

Psychiatric Symptoms

• Anxiety, depression, irritability, and confusion can occur due to hypocalcemia
• Psychosis and dementia are rare but possible psychiatric symptoms of hypocalcemia

Causes of Hypercalcemia

• Primary hyperparathyroidism is a cause of hypercalcemia
• Malignant diseases can cause hypercalcemia through: • Production of parathyroid hormone-related protein • Ectopic production of 1,25-dihydroxyvitamin D • Release of bone-resorbing substances • Osteolytic bone metastasis
• Certain medications can cause hypercalcemia, including: • Thiazide diuretics • Lithium • Estrogens • Vitamin D toxicity • Vitamin A toxicity • Calcium ingestion

Granulomatous Disorders

• Granulomatous disorders can cause hypercalcemia, including: • Sarcoidosis • Tuberculosis • Coccidioidomycosis • Berylliosis • Histoplasmosis • Leprosy

Non-Parathyroid Endocrine Disorders

• Certain endocrine disorders can cause hypercalcemia, including: • Hyperparathyroidism • Adrenal insufficiency • Pheochromocytoma • Acromegaly • Vasoactive intestinal polypeptide-producing tumor

Miscellaneous Causes

• Other causes of hypercalcemia include: • Milk-alkali syndrome • Immobilization • Idiopathic hypocalcemia of infancy

Neurological Symptoms of Hypercalcemia

• Fatigue, weakness, and lethargy may occur due to hypercalcemia
• Confusion and seizures are potential neurological symptoms
• Hypotonia, characterized by decreased muscle tone, can be a sign of hypercalcemia
• Diminished deep tendon reflexes may indicate hypercalcemia
• In severe cases, hypercalcemia can lead to coma

Cardiovascular Symptoms of Hypercalcemia

• Hypercalcemia can cause hypertension
• Electrocardiogram changes include ST segment elevation, sinus bradycardia/arrest, and AV block
• A short QT interval is a potential cardiac symptom
• Bundle branch block (BBB) can occur in hypercalcemia
• Ventricular dysrhythmias, including ventricular tachycardia and fibrillation, are potential complications
• Hypercalcemia can potentiate digoxin toxicity

Renal Symptoms of Hypercalcemia

• Polyuria (excessive urine production) and polydipsia (excessive thirst) are common symptoms
• Dehydration can occur due to excessive urine production
• Electrolyte imbalance and loss of electrolytes are potential complications
• Prerenal azotemia, a type of kidney failure, can occur in hypercalcemia
• Nephrolithiasis, the formation of kidney stones, is a potential complication
• Nephrocalcinosis, the deposition of calcium in the kidneys, can occur in hypercalcemia

Gastrointestinal Symptoms of Hypercalcemia

• Nausea and vomiting are common gastrointestinal symptoms
• Anorexia, or loss of appetite, can occur in hypercalcemia
• Peptic ulcers, which are sores in the lining of the stomach or duodenum, can be a complication
• Pancreatitis, or inflammation of the pancreas, can occur in hypercalcemia
• Constipation and ileus, a condition in which the intestine fails to function, can be gastrointestinal symptoms

Phosphate Distribution

• 85% of phosphate is found in the bone, with a small amount in the plasma

Phosphate Forms in Plasma

• Phosphate exists in plasma as:
  • Phospholipids
  • Phosphate esters
  • Inorganic phosphate (ionized form)

Intracellular Phosphate Functions

• Component of ATP
• Component of 2,3 DPG
• Acts as a buffer in acid-base balance

Phosphate Regulation

• Phosphate concentration in plasma is inversely proportional to calcium concentration
• Regulated by same mechanisms as calcium, including:
  • PTH (parathyroid hormone)
  • Vitamin D
  • Calcitonin

Treatment of Phosphate Imbalances

• Hypophosphatemia: treated with oral or IV supplementation
• Hyperphosphatemia: treated with aluminum hydroxide, which binds phosphate in the GI tract

Hypophosphatemia

• Defined by a blood phosphorus level of 4.7 mg/dL or lower
• Causes include:
  • Acute or chronic renal failure
  • Treatment of metastatic tumor
  • Long-term use of laxatives or enemas containing phosphates
  • Hypoparathyroidism
• Complications include:

  Symptoms related to hypocalcemia

  • Chronic calcification of soft tissues
  • Affected tissues include:
    • Joints
    • Lungs
    • Kidneys

Hypomagnesemia (Low Magnesium Levels)

• Normal range of magnesium levels in the body is 1.5-3 mEq/L.
• Regulation of magnesium levels occurs in the intestines and kidneys.
• Magnesium plays a crucial role in various bodily functions, including enzymatic processes, Na/K pump, protein synthesis, and nerve-muscle excitability.

Causes of Hypomagnesemia

• Renal loss: renal failure, postobstructive diuresis, tubular necrosis, glomerulonephritis, interstitial nephropathy, transplant.
• GI loss: chronic diarrhea, NG suction, short-bowel syndrome, protein-calorie deficit, bowel fistula, TPN, pancreatitis.
• Endocrine disorders: DM, hyperaldosteronism, hyperthyroidism, hyperparathyroidism, acute porphyria.
• Medications: aminoglycosides, amphotericin, beta-agonists, cisplatin, cyclosporine, diuretics, foscarnet, pentamidine, PPI, theophylline.
• Congenital: familial hypomagnesemia, maternal diabetes, maternal hypothyroidism, maternal hyperparathyroidism.
• Miscellaneous: pregnancy, excessive alcohol intake, citrate binding with blood administration.

Symptoms and Treatment of Hypomagnesemia

• Symptoms: inhibits Na/K pump, decreasing ICV K, N/V, tetany, flat T-waves, U-waves, prolonged QT, wide QRS, arrhythmias.
• Treatment: 1-2 g IV magnesium sulfate over 5 minutes, followed by 1-2 g/hr. IV infusions can also relieve severe bronchospasm, arrhythmias, and decrease post-operative pain.

HYPERMAGNESEMIA

• Occurs due to overadministration during treatment of preeclampsia, preterm labor, ischemic heart disease, and dysrhythmias
• Potentiates the action of nondepolarizing neuromuscular blockers (NMB)

Treatment of HYPERMAGNESEMIA

• Involves stopping the magnesium infusion (if given)
• In urgent situations, calcium gluconate 10-15 mg/kg can be given as an antagonist

HYPERMAGNESEMIA Causes and Manifestations

• Caused by renal failure, excessive magnesium administration, and adrenal insufficiency
• Manifestations vary by serum level:
  • 4-5 mmol/L: decreased deep tendon reflexes (DTR)
  • 5-7 mmol/L: hypotension
  • 10 mmol/L: respiratory paralysis and coma
  • 10-20 mmol/L: heart block and cardiac arrest

Magnesium Uses

Preeclampsia

• Improves symptoms by systemic, vertebral, and uterine vasodilation via direct effects and increasing concentrations of endogenous vasodilators
• Typically administered as 4 g IV load over 15 minutes, followed by 1 g/hr for 24 hours
• Crosses the placenta, potentially causing neonatal lethargy, hypotension, and respiratory depression

Dysrhythmias

• Blocks calcium influx, decreasing SA node activity and prolonging AV conduction time
• Recommended for treating torsade's de pointes

Analgesia

• Functions as a calcium and NMDA antagonist

Asthma

• Induces bronchodilation via calcium inhibition in smooth muscle

Pheochromocytoma

• Reduces catecholamine release and dilates vasculature