PHAR359

Electrolyte, other minerals & trace elements 1

Alla El-Awaisi MPharm, MRPharmS, MSc 10th October 2011

Learning Objectives
Describe the homeostatic mechanisms involved in sodium and water balance, hyponatremia, and hypernatremia. Describe the physiology of intracellular and extracellular potassium regulation, and the signs and symptoms of hypokalemia and hyperkalemia. List common causes of serum chloride abnormalities. List common conditions resulting in serum magnesium abnormalities and describe signs and symptoms of hypomagnesaemia and hypermagnesaemia.
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Distribution of Body Solids & Fluids

We are approximately two-thirds water.

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Varies slightly depending on such factors as the persons age, lean body mass, and sex.

Composition of Body Fluids

ECF and ICF contain oxygen from the lungs, dissolved nutrients from the GI tract, excretory products of metabolism such as CO2, and charged particles called ions. An ion is an atom or molecule carrying an electrical charge. Substances capable of breaking into electrically charged ions when dissolved in a solution are called electrolytes. 1. Cations: Ions that develop a positive charge. 2. Anions: Ions that develop a negative charge These charges are the basis of chemical interactions in the body necessary for metabolism and other functions.

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Osmolality
Because a hypertonic solution has a greater osmolality, water moves out of the cells and is drawn into the intravascular compartment, causing the cells to shrink. Due to a lower osmolality, a hypotonic solution in the intravascular space moves out of the intravascular space and into intracellular fluid, causing cells to swell and possibly burst. Normal serum osmolality is usually between 280295 mOsm/kg H2O. The presence of a significant amount of other extracellular solutes (e.g., alcohol, glucose, and organic solvents) can further elevate serum osmolality, thus affecting body water and sodium status.
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Maintaining Homeostasis
Fluid homeostasis normally functions automatically and effectively. Almost every organ and system in the body helps in some way to maintain fluid homeostasis. Fluid balance is threatened when any organ fails to function properly. The kidneys, frequently referred to as the master chemists of the body, normally filter 135 to 180 L of plasma daily in the adult, while excreting only 1.5 L of urine; selectively retain electrolytes and water and excrete wastes and excesses.

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 As a result of changes in effective circulating volume, baroreceptors and osmoreceptors will respond accordingly in an attempt to restore an isovolemic state of the body. Baroreceptors are located in the carotid sinus, aortic arch, cardiacatria, hypothalamus, and the juxtaglomerular apparatus in the kidney. Stimulation of these receptors will promote urinary loss of water and sodium. Osmoreceptors are present primarily in the hypothalamus.

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Fluid Volume Disturbances

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Fluid Volume Deficit (Hypovolemia)

Fluid Volume Disturbances 2

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Fluid Volume Excess (Hypervolemia)

Fluid Volume Disturbances 3

Hypovolemia Pathophysiology results from loss of body fluids and occurs more rapidly when coupled with decreased fluid intake Insufficient intake, vomiting, diarrhea, hemorrhage. Oliguria, Concentrated urine, Postural hypotension, Weak, rapid, heart rate, Flattened neck veins, Increased temperature, Decreased central venous pressure. Hypervolemia Pathophysiology may be related to fluid overload or diminished function of the homeostatic mechanisms responsible for regulating fluid balance Contributing factors CHF, renal failure, cirrhosis. Clinical manifestations edema, distended neck veins, crackles, tachycardia, increased blood pressure, increased weight
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Normal Dietary Intake of Electrolyte, Other Minerals, and Trace Elements

Nutrient Sodium
Potassium Chloride Magnesium Calcium Phosphate Copper Zinc Manganese Chromium

Normal Daily Dietary Intake

50-100 mEq Varies with potassium and sodium intakes 300-400mg ^1000mg 700-800g 2-5mg 4-14mg 3-4mg 50-100mcg
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Highly variable; average 5.6-7.2g

Lau A, Chan LN . Electrolytes, Other minerals, and trace elements. Chapter 6, p. 119 - 160

Electrolytes are important for:

Maintaining fluid balance
Contributing to acid-base regulation Facilitating enzyme reactions Transmitting neuromuscular reactions.
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Electrolyte
Most electrolytes enter the body through dietary intake and are excreted in the urine. Some electrolytes, such as sodium and chloride, are not stored by the body and must be consumed daily to maintain normal levels. Potassium and calcium, on the other hand, are stored in the cells and bones, when serum levels drop, ions can shift out of the storage into the blood to maintain adequate serum levels for normal functioning.
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Sodium
Sodium is the most abundant cation in the extracellular fluid Normal range 136 to 145 mmol/L Primary regulator of ECF volume (a loss or gain of sodium is usually accompanied by a loss or gain of water). Major contributor to serum osmolality. Serum osmolality is an estimate of the water-solute ratio in the vascular fluid. It is useful in determining volume status, especially the intravascular volume.
Sodium is unique among electrolytes because water balance, not sodium balance, usually determines its concentration
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Sodium Function
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http://www.youtube.com/watch?v=W3t8gtN-Wfk

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Causes
Hyponatremia
Diet Water Retention Diuretics Hypoaldosteronism Excessive ADH: SIADH Nausea

Hypernatremia
Sweating Water Loss Too much sodium in diet. Decreased ADH
Alcohol Hyperaldosteronsim. Diabetes insipidus
Central Nephrogenic
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What are the clinical features of .?

Hyponatremia
Cells swell Cells hyperpolarize CNS dysfunction Cardiac Dysfunction Muscle weakness Decrease blood volume Stimulates Na+ driven PCT reuptake

Hypernatraemia
Cell shrink Cells depolarize Increase blood pressure CNS dysfunction Muscle cramping Lethargy Seizures Inhibit Na+ driven PCT reuptake.
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Hyponatremia (> 136mmol/L) Overall decrease in Na+ in ECF

Depletional (extracellular volume deficit)
Na+ loss:

Decreased intake
Low sodium diet Enteral feeds

Loss of Na containing fluids

GI losses (vomiting, NGT, diarrhea) Renal losses (diuretics or primary renal disease Decreased aldosterone Iatrogenic High ADH (increases reabsorption of free water, causing increase in volume and hypoNa)
SIADH- low serum Na, high Urine Na and U Osm

Renal dysfunction with intake of hypotonic fluids Excessive sweating increased thirst intake of excessive amounts of pure water
High ADH (increases reabsorption of free water, causing increase in volume and hypoNa)
SIADH- low serum Na, high Urine Na and U Osm

Oliguric renal failure, severe congestive heart failure, cirrhosis all lead to: Impaired renal excretion of water Hyperglycemia attracts water (Excess
solute relative to free water (ie: hyperglycemia). Drugs causing water retention

Antipsychotics, tricylcic antidepressants, ACE inhibitors

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Dilutional (Excess extracellular water/ volume)

Fractional Excretion of Sodium (FENa)

Normal range: 1% to 2%
Is abnormality associated with low, normal, or high total body sodium? The FENa may be determined by the use of a random urine sample to determine renal handling of sodium. FENa: the percentage of filtered sodium excreted in the urine.

<2% usually suggest that the kidneys are excreting a higher than normal fraction of the filtered sodium, implying likely renal tubular damage. >1% generally implies renal sodium retention, suggesting prerenal causes of renal dysfunction (e.g., hypovolemia and cardiac failure).

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Categorizing hypernatremia < 145 mmol/L

Similar to hyponatremia, hypernatremia may occur in the presence of high, normal, or low total body sodium content

Homeostasis of water and sodium Pathways:

1. Vasopressin or antidiuretic hormone (ADH). 2. Renin-angiotensin-aldosterone system (RAAS). 3. Natriuretic peptides.
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Homeostatic mechanisms involved in sodium, potassium, and water balance.

Lau A, Chan LN . Electrolytes, Other minerals, and trace elements. Chapter 6, p. 119 - 160

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Water Deprivation

Drink Water Plasma Osmolality Activation of osmoreceptors in anterior hypothalamus ADH secretion from Post. Pituitary

Water permeability in late DT and CT

Water Reabsorption

Urine Osmolality

Urine Volume

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Water Loading
Drink Water Plasma Osmolality Activation of osmoreceptors in anterior hypothalamus ADH secretion from Post. Pituitary

Water permeability in late DT and CT

Water Reabsorption

Urine Osmolality

Urine Volume

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Altering the amount of water reabsorbed by the kidney has a pivotal effect on serum sodium concentration.

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ADH Abnormalities
Syndrome of inappropriate ADH secretion (SIADH) An abnormally high quantity of ADH is present. This condition results in increased water reabsorption. In conjunction with an increased free water intake. Central diabetes insipidus (DI) Occurs when hypothalamic ADH synthesis or release is impaired. In some cases, the kidneys fail to respond to normal or high quantities of circulating ADH. This condition is called nephrogenic diabetes insipidus. In central or nephrogenic diabetes insipidus, little water reabsorption occurs, resulting in a large urine output with low urine osmolality.
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Finding the problem

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Look at the urine Look at the serum sodium

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Disorder
SIADH

Serum Na+

Serum Osmo

Urine Osmo

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Dehydration
Diabetes Insipidus

So what's the problem???

Because of their ability to increase ADH release, some of these drugs are used in the treatment of central DI.

Lau A, Chan LN . Electrolytes, Other minerals, and trace elements. Chapter 6, p. 119 - 160

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Homeostasis of water and sodium Pathways:

1. Vasopressin or antidiuretic hormone (ADH). 2. Renin-angiotensin-aldosterone system (RAAS) 3. Natriuretic peptides.
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2. Renin angiotensin aldosterone system on Na+ excretion

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3. Atrial natriuretic peptide on Na+ excretion

ANP actions: 1. Na+ reabsorption from deep medullary collecting duct 2. glomerular filtration rate Both actions Na+ excretion
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Sweating on salt & water excretion

Extracellular fluid volume

Extracellular osmolality thirst

Water reabsorption

Water excretion

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ADH secretion

Im not fat Im just really swollen from the salt in my chili cheese fries

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Potassium (K+)
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Most prevalent cation in the intracellular fluid. 98% of the bodys potassium is inside the cells Normal serum potassium concentration : 3.5 to 5.0 mmol/L. Hypokalemia is an abnormally low potassium level (less than 3.5mmol/L). Hyperkalemia is an abnormally high potassium level (greater than 5.5 mmol/L). It is more dangerous than hypokalemia because cardiac arrest is frequently associated with high serum K+ levels. One of the few things you can die from without any symptoms

Regulation of muscle and nerve excitability Acid Base Balance Acidosis/ Alkalosis
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Potassium
Na+, K+-ATPase Contractility of cardiac, skeletal, and smooth muscle. Effect on Cardiac muscle is the most important due to the potential life threatening effect of arrhythmias.

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Insulin

Changes in Acid base balance Aldosterone

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Potassium Homeostasis

GI and skin Losses

Renal function

Potassium Homeostasis (1)

Na+, K+-ATPase maintains the high intracellular K+ concentration
Pumping Na+ out of the cell and K+ into the cell.
Insulin activates the Na+, K+-ATPase- drives K+ into the cell Acidosis (high H+) drives potassium extracellularly; (H+ in for K+ out) Alkalosis drives K+ into the cell -Adrenergic agonists stimulate the Na+, K+-ATPase, cellular uptake of K+ -Adrenergic agonists and exercise cause a net movement of K+ out.
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Quick way: Shift the plasma potassium into cells

CELLULAR-EXTRACELLULAR SHIFTS Insulin deficiency predisposes an individual to hyperkalemia Cellular uptake of K+ ions is enhanced by insulin. Provides protection from extracellular K+ overload
Insulin

K+ K+ K+

K+ K+

Click to view animation

K+

Potassium Homeostasis (2)controlled by EXCRETION

Kidney plays the most important role
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90% is of K+ is resorbed before the distal tubule and collecting duct In distal tubule and collecting duct- K+ absorbed and secreted while sodium is reabsorbed. Tubular secretion that regulates the amount of K+ in the urine Potassium secretion is influenced by: Aldosterone. Delivery of large quantities of sodium and fluid to the distal tubules . Presence of anions in the distal tubules. Potassium concentration in distal tubular cells. Serum pH.

Alkalosis: hypokalemia (>3.5mmol/L) Acidosis: hyperkalemia (<5.0mmol/L)

Lau A, Chan LN . Electrolytes, Other minerals, and trace elements. Chapter 6, p. 119 - 160

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CLINICAL MANIFESTATIONS
Hypokalemia Hyperkalemia

Hyperpolarization CNS Dysfunction Cardiac Dysfunction Muscle Weakness Respiratory Arrest

Depolarization CNS Dysfunction Restlessness Cardiac Dysfunction Diarrhea

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The ACUTE homeostatic sequence of events in the body to maintain serum potassium within a narrow concentration range.

Lau A, Chan LN . Electrolytes, Other minerals, and trace elements. Chapter 6, p. 119 - 160

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