MT 120 LECTURE 1: ELECTROLYTES

Lectured by: Lovelyn Mae E. Cuison, RMT, MSMT

Objectives:
 Determine the clinical significance of electrolytes  Correlate the causes and abnormal levels of electrolyte results
 Determine the physiology and clinical applications of each electrolyte

Electrolytes
 Ions capable of carrying an electric charge.
 Electrolytes are classified as either cations (+) or anions (-), based on the type of charge
that they carry, and also based on how these electrolytes migrate in an electric field
o (+) charge→ (-) pole (cathode) o (-) charge→ (+) pole (anode)
 Key Functions of Electrolytes

Water Balance and Distribution

 40-75%= average water content of the human body (these values decrease as the person ages, and also in terms of obesity)
o Comparing males and females physiologically, women have lower average water content than men as a result of higher fat content.
 Water is the solvent for all processes in the human body (called as the universal solvent)
 Functions:
o Transports nutrients to cells (so it can do its function, because 90% of the fluid portion of the blood is water)
o Determines cell volume by its transport into and out of cells (balances the concentration of substances in and out of the cell to
maintain the cell volume, like in the processes of diffusion or osmosis)
o Removes waste products by way of urine o Acts as body’s coolant by way of sweating
 Water Compartments in the Body
o Blood inside of a test tube is centrifuged and the RBC settles at the bottom, and around it is the fluid portion of the blood (plasma).
The electrolytes K+, Mg2+, and PO43- are inside of the cell. Outside of that (in the plasma) are extracellular cations Na 2+ (main
extracellular cation), Cl-, and HCO3-. 60% of total body’s water is inside of the cells, and the rest is in the bloodstream/tissue fluids.
o Intracellular Fluid (ICF)
 Found inside the cells.  Approximately 60% (24 L) or 2/3 of total body water
 Main electrolytes: K+, Mg2+, and PO43-
o Extracellular Fluid (ECF)
 Found outside the cells.  Approximately 40% (16 L) or 1/3 of total body water
 Main electrolytes: Na2+ (main extracellular cation), Cl-, and HCO3-
 Fluid shifts that occur during changes in hydration, or in the intake of water can have a marked effect, particularly on the ECF
 In most disease states, loss of fluids occurs initially from the extracellular fluids. Examples: Diarrhea
(large volume of GI fluid that is lost), and Renal failure (large of volume of ECF may be excreted)
 It is important to be able to estimate the volume of the extracellular fluid compartment and also the
volume of fluid lost to initiate appropriate fluid replacement and to monitor fluid therapy.
 3 compartments
 Interstitial Fluid- Fluid found between the cells and blood vessels
 Intravascular Fluid- Fluid found inside of the vasculature (blood vessels); main fluid in the compartment: plasma
 Transcellular Fluid- Fluid inside the epithelial-lined spaces (e.g. CSF, pericardial fluid, and synovial fluid)
o Note:
 About 30 L of fluid passes from the blood to the tissue spaces daily.
 Normal plasma is composed of 93% of water (plasma is the main intravascular fluid) and 7% solutes (such as glucose, lipids
proteins, NPNs, amino acids, ions such as electrolytes).
 Water content of plasma is 12% higher than that of the whole blood.
 Retention of 3 L of fluid in the tissues will result to edema.
 Deficiency of vasopressin (anti-diuretic hormone/ADH) causes 10-20 L of water excreted daily.
 Salt content of the body is the main determinant of the extracellular volume.
 Sweat contains about 50 mmol/L of sodium and 5 mmol/L of potassium.
o Sources of Body Water
 Water inside the body is taken through consumption, or it is produced by metabolism.
 Drinking is a major route of water intake.
 For water losses, normally, an average adult would lose about 2500 mL of water each day through excretion.
 1500 mL- lost in the urine through urination
 1000 mL- insensible losses (e.g. sweating, perspiration or exhalation of water vapor through the lungs, or excretion from the
intestine with fecal material), compensated by consuming water
 Average adult consumes about 1000 mL of water a day (average water level taken in every day). Depending on the diet, another
1000-1200 mL/day of water enters the body from food.
 Water is also generated as part of several biochemical processes (water of oxidation).
 100 grams of fats metabolized= 100 mL of water  100 grams of proteins oxidized= 44 mL of water
  Oxidation of 100 grams of carbohydrates= 60 mL of water

Regulation of Blood Volume

 Renin Angiotensin Aldosterone System (RAAS)- Involves the sympathetic nervous system, which is also involved in the
stimulation of activities that prepare the body for action (e.g. increasing the heart rate, increasing the release of sugar from the liver
into the blood, and other generally considered as a fight or flight responses).
 Important because once blood volume is regulated, it follows that the blood pressure and perfusion (blood flow to all tissues and
organs) will also be maintained.
 Regulation of both sodium and water is interrelated in controlling the blood volume.
 3 organs that maintain the function of this entire system: Kidneys, Liver, and Lungs
o Low blood volume/Low blood pressure→ renin will be released from the kidneys (in the juxtaglomerular apparatus)
 Activates the entire system of RAAS
o Renin (angiotensinogenase)- an enzyme produced from the kidney that will stimulate the liver
o Once renin is released from the kidneys, it will send a signal to another organ (liver) to produce another substance,
angiotensinogen.
o Once angiotensinogen is produced from the liver, it will be converted to another substance, angiotensin I.
 Angiotensinogen is converted to angiotensin I by the renin; still inactive (needs to be activated).
o The surface pulmonary and renal endothelium will produce an enzyme, called as Angiotensin Converting Enzyme (ACE), which
will convert angiotensin I (inactive form) to angiotensin II (its active form).
o Angiotensin II will send signal to the sympathetic nervous system to generate its activities (e.g. increasing the heart rate and
increasing the blood sugar, so that the BP will also be increased to its baseline level).
 Angiotensin II will also help in the reabsorption of sodium and chloride, excretion of potassium, and the retention of water.
 It will stimulate the adrenal gland (on top of the kidneys), particularly the adrenal cortex to produce a hormone known as
aldosterone (2 main functions: ↑ Na in the blood, ↓ K in the blood)
 Helps in the reabsorption of sodium, so that it will be increased in the blood.
 Helps in the excretion of potassium, so it will be decreased in the blood.
 It will also activate the process of vasoconstriction, so once the vessels are
constricted, then it will increase the blood pressure (since there is a low BP).
 It can also stimulate the posterior lobe of the pituitary gland to produce
another hormone, antidiuretic hormone (ADH).
 ADH mainly functions by stimulating the collecting duct of the kidney to
reabsorb water (↑ ADH leads to ↑ water level; ↓ ADH leads to ↓ water level)
o If these functions are already maintained and if the BP and blood volume are already returned to its baseline level, then it will send
a negative feedback to the kidney to stop the production of renin.

Major Electrolytes of the Body

 Sodium (Na2+)
o Also known as “natrium”.
o Most abundant extracellular cation (as opposed to potassium, which is the major intracellular cation).
 Outside the cell, sodium is the major extracellular cation, and inside the cell, potassium is the major intracellular cation.
 The concentration of sodium in the ECF is much greater than the ICF, whereas the potassium is greater inside the cell.
 Na and K can readily diffuse through the cell membrane (can diffuse in and out of the cell) so the 2 sides of the cell would
eventually reach equilibrium. In order to prevent equilibrium from happening, there are active transport systems such as Na-K
ATPase pump
 Na-K ATPase pump is a type of active transport system which would move 3 Na ions out of the cell in exchange for 2 K ions
into the cell, as the ATP is converted to ADP.
o Largely determines the osmolality of the plasma.
 Osmolality reflects the ion concentrations in the blood
 Normal plasma osmolality: 295 mmol/L→ 270 mmol/L is because of Na and other associated ions
o Regulates water balance in the body (wherever sodium goes, water follows).
 Since water follows Na across the cell membranes, the continual removal of Na from the cell prevents osmotic rupture of the cell
by also drawing water from the cell.
o Its plasma concentration depends greatly on the intake and excretion of water.
o Reference range: 135-145 mmol/L or 135-145 mEq/L (for serum) or 136-150 mmol/L or 136-150 mEq/L (for CSF)
o Renal threshold/Threshold critical value: 160 mmol/L (hypernatremia); 120 mmol/L (hyponatremia)
 Renal threshold means the concentration level up to which a substance (Na in the blood) is prevented from passing through the
kidneys into the urine.
o Hormones Affecting Sodium Levels
 Aldosterone
 Sodium retention by increasing its reabsorption in the DCT and increases potassium excretion.
 In some diseases when there is a very high aldosterone, that would not only lead to increased sodium, but also potassium
wasting.
  Atrial Natriuretic Peptide (ANP)
 An endogenous anti-hypertensive agent secreted by the cardiac atria.
 Blocks aldosterone and renin secretion
 Has an opposite effect to aldosterone because whenever ANP is released, aldosterone is inhibited. It lowers Na and increases
K.
 In the RAAS, renin increased BP and blood volume, but the ANP will suppress the action of renin (anti-hypertensive agent)
 Inhibits the action of angiotensin II and vasopressin (ADH) resulting to natriuresis.
 Natriuresis is the excretion of sodium in the urine.
o Sodium Regulation
1. Depends on the intake of water in response to thirst (if plasma osmolality is ↓)
2. The excretion of water is largely affected by ADH 3. Blood volume status through RAAS and ANP
release
o Clinical Applications
 Hyponatremia (↓blood Na levels; Na <135 mmol/L, most common electrolyte disorder)
 Clinically, if the sodium falls <130 mmol/L, that is already considered as clinically significant
 Top Causes:
1. Overhydration- relative decrease of Na because of increased water intake
2. Diuretic use and abuse- initially, there are two types of diuretics: thiazide diuretics (acts on the distal tubule of the nephron)
and loop diuretics (acts on the Loop of Henle itself); if there is diuretics abuse, this will induce Na-K loss without interfering
with ADH-mediated water retention
In the ascending Loop of Henle, there is a Chloride pump, which actively transports chloride back to the interstitium
(initiates chloride reabsorption). It increases the chloride in the interstitium, and because Na passively follows Cl -, so there is
an increased Na level if the chloride pump is functioning well.
If the chloride pump is blocked (e.g. no reabsorption of chloride to the interstitium), it will lead to a decrease in Cl - and Na
levels. If the Cl- and Na decreases, then that would also mean a decrease in osmolality. No Cl - will be reabsorbed, and since
Na passively follows Cl-, then no Na will be reabsorbed, leading to a decrease in Na and Cl -. Since Na largely determines the
osmolality of the plasma, that means there will be a decreased osmolality. However in this case, the ADH is not activated
because the ADH release is triggered by an increased osmolality in the interstitium, so in this case there is a decrease
osmolality so ADH will not be released and there will be no water retention.
3. SIADH (Syndrome of Inappropriate ADH Secretion)- there is increased ADH (vasopressin), so a lot of water will be
reabsorbed in the collecting duct, which will decrease the Na level
4. Adrenal failure- in the RAAS system, there is the action of angiotensin II, which would stimulate the adrenal cortex to release
aldosterone, but in cases of adrenal failure, the adrenal cortex cannot produce aldosterone either because of tumors or
destruction of the adrenal cells, leading to a decrease in Na and increase in K
5. Bartter’s syndrome- this condition is caused by a defect in the kidneys’ ability to reabsorb Na
In this the defect, the ascending limb could not reabsorb Na, and people affected by this syndrome lose too much Na through
the urine, that is why it leads to decreased Na. Because there is a decrease in Na in the blood because of too much loss of Na
in the urine, that will now lead to an increased aldosterone level.
There is also K wasting because more aldosterone is produced as a compensation of the losses of the Na in the urine, that is
why also the K will be excreted.
This also resembles diuretics abuse except that the decrease in Na is not corrected with fluid restriction.
6. Diabetic hyperosmolarity- In cases of diabetes mellitus, when the osmolality of the ECF increases because of hyperglycemia,
the water will go out of the cell because of increased osmolality (water will go out of the cell), which will lead to a dilution of
serum Na.
For every 100 mg/dL increase in serum glucose= 1.6 mEq/L decrease in Na
 Causes of Hyponatremia
 Hypovolemic Hyponatremia- results from sodium loss in excess of water loss (hypovolemic state and low Na level in blood)
Renal loss (excretion of Na >20 mmol/day)
 Diuretics- in the ascending Loop of Henle, there is a chloride pump which actively transports Cl - back to the interstitium,
so the Cl- is reabsorbed and since Na passively follows Cl -, the Na is also reabsorbed back (normal mechanism). However
in the use of diuretics, the chloride pump is being blocked so there will be no chloride reabsorption, so Cl - is decreased, and
since Na follows Cl-, so there is also a decrease in Na level, and because of these levels of these electrolytes, there is also a
decrease in osmolality (ADH not activated and no water retention because the ADH release is triggered by an increased
osmolality in the interstitium and not a decrease in osmolality)
 Potassium depletion- when the K is depleted, the Na will move into the cell as a compensation for the loss of Na (plasma
Na will decrease) that will lead to hypovolemia
 Aldosterone deficiency- if aldosterone is deficient, then it follows that Na reabsorption is also hindered
 Ketonuria (DM)- the sodium loss occurs with this condition, diabetic hyperosmolality
 Salt-losing nephropathy (e.g. polycystic kidney diseases)
Extra-renal loss or Cellular shift (excretion of Na <20 mmol/day)
 Vomiting  Excess fluid loss (burns, sweating, trauma)
 Diarrhea  Potassium depletion
 In these instances, thirst is stimulated by hypovolemia, so that results in replacement by relatively more hypotonic fluid
  Normovolemic Hyponatremia
Causes
 SIADH- increased secretion of ADH, there will be retention of water (↑ H 2O), which leads to ↓ Na levels because the Na
will be diluted in the plasma due to the increased water level
 Usually secondary to head trauma, seizures, or CNS diseases and neoplastic conditions that secrete ADH-like hormones
 Normally would initiate mild hypervolemia (↑ H 2O levels)→ triggers the release of ANP (blocks the aldosterone, and if
aldosterone is being blocked, Na will not be reabsorbed, resulting to a ↓Na and ↓H2O levels)
 Pseudohyponatremia (artifactual hyponatremia)- usually occurs in cases of severe hyperlipidemia or hyperproteinemia;
there is ↑ lipids and ↑ proteins; no Na ions are dissolved in lipids, which can take up a considerable volume of serum
(therefore the decrease of Na is relative or secondary to hyperlipidemia or hyperproteinemia)
 Severe hyperglycemia- induces water movement to plasma to normalize the osmolality
 Excess water intake- use of hypotonic fluid/psychogenic polydipsia
 Adrenal insufficiency- leads to a ↓ aldosterone and also ↓ cortisol, because cortisol is also produced from the adrenal
gland, and cortisol inhibits the ADH release, so if the ADH is inhibited then no
water is being retained; the initial phase of this process results in hypovolemia,
however the ADH-induced water retention typically restores volume status to
normal
 Pregnancy
 Hypervolemic Hyponatremia
Nearly always a problem of water overload, which causes edema.
Na >20 mmol/day- acute or chronic renal failure
Na <20 mmol/day- nephrotic syndrome, hepatic cirrhosis, congestive heart failure
Usual therapy: water restriction, Na should not be given (because it could increase the severity of edema)
 Example: In congestive heart failure and hepatic cirrhosis, there is an increased venous blood pressure in the circulation,
which would promote movement of fluid from the blood to the interstitium, causing edema.
 Serum and Urine Electrolyte Patterns in common causes of hyponatremia (Normal renal function)
 Overhydration- caused by consumption of large amount of water or hypotonic fluids
Because the consumed water is excreted by the kidneys, the urine is also diluted.
There is a triad of ↓ Na level, ↓ Hct values, and ↓ BUN
The serum K can also be low, but it often remains within the reference range (normal or ↓ K levels)
Since mainly water is excreted in the urine in this condition, the total 24-hour Na excretion will also be low ( ↓ 24-h urine
Na)
 Diuretic abuse- the loop diuretics usually block the chloride pump in the Loop of Henle
The chloride pump is necessary for water conservation. If this pump is blocked, water is lost and Na is depleted, because it
follows Cl- in the loop.
The loop diuretics could result to severe potassium depletion (unless drugs or substances that could spare potassium was
used)
The total 24-hour Na excretion is high (unlike in overhydration)
 SIADH
Serum Na is decreased because of excessive retention of water in the collecting ducts because of ↑ ADH levels, which results
in the depletion of water in the renal tubules (this concentrates the urine)
 Adrenal failure- usually secondary to Addison’s disease (no aldosterone)
Since there is no aldosterone, the exchange of Na and K in the DCT and collecting ducts does not occur, there will be ↓
serum Na concentration and ↑K concentration (owing to the function of the aldosterone)
Urinary sodium is mildly ↑ (as opposed to SIADH, that is very high, difference between SIADH)
 Barter’s syndrome- resembles diuretics use and abuse
The only difference from diuretics abuse is that hyponatremia is not corrected with fluid restriction in Barter’s syndrome,
and in this case, the kidneys of the patients fail to retain K (↓K and ↓Na, hyponatremia accompanied by hypokalemia)
 Diabetic hyperosmolarity- when the osmolality of the ECF increases because of increased blood glucose, water will go out of
the cell, that would result to the dilution of serum Na
 Hypernatremia (↑blood Na levels; Na >145 mmol/L or 145 mEq/L)
 Causes:
1. Excess loss of water relative to sodium loss 3. Increased sodium intake
2. Decreased water intake
 Specific causes: Dehydration, Diabetes insipidus, and Hyperaldosteronism
 Major defense of the body to hypernatremia and hyperosmolality: activation of thirst in which the osmoreceptors in the
hypothalamus will respond to the elevated blood osmolality by triggering the sensation of thirst and by increasing the secretion
of antidiuretic hormone (ADH).
 Dehydration- one of the main causes of hypernatremia
Profuse sweating or breathing- insensible losses, could account for about 1L of water loss per day in adults
Diarrhea Severe burns
Conditions that increase water (e.g. fever, burns, and exposure to heat)
 Can occur in adults with altered mental status and also in infants, because they can be thirsty, but they are unable to ask
for water or obtain water by themselves.
Note: Serum sodium is elevated and the urine sodium is also high due to increased renal secretion of NaCl.
 Diabetes Insipidus (DI)
Characterized by copious production (high in amount/volume) of dilute urine (because there is too much excretion of water,
usually the urine is diluted, and the volume of urine excreted is about 3-20 L/day)
Absence of ADH function results to inadequate water retention (if ADH is defective or if there are factors that contribute to
loss of function of ADH, water will not be retained, leading to an increased urine output, which is diluted)
Increased serum sodium (but decreased urinary sodium because of dilutional effect) due to water loss, relative increase
Neurogenic DI (decreased ADH secretion)
 Posterior pituitary gland releases ADH/vasopressin→ acts on the collecting duct of the kidneys in order to reabsorb water
 Decreased ADH secretion- there is a problem in the pituitary gland, which results in ADH to not be released
 The collecting duct will not be stimulated, so water retention will not occur→ leads to ↑urine volume but ↓specific gravity,
because of dilutional effect
Nephrogenic DI (decreased renal response)
 The pituitary gland is functioning well (it could release ADH), but it is the kidney that has problem.
 The collecting duct is not responsive to the ADH production, so water reabsorption will also not occur→ leads to ↑urine
volume with ↓specific gravity (differentiates DI from DM, which has also polyuria- ↑urine volume with ↑specific gravity)
To differentiate Neurogenic DI from Nephrogenic DI (which has same signs and symptoms): Vasopressin administration
 Neurogenic DI will respond to vasopressin- if the patient is given vasopressin, this will be corrected and the collecting duct
could respond to vasopressin administration and water could be reabsorbed
 In cases of Nephrogenic DI, despite of the administration of vasopressin, still the kidneys are the problem so even if
vasopressin is administered, the kidneys will still not respond to it so water will still not be reabsorbed
 Hyperaldosteronism
Adrenal hyperplasia- a genetic disorder that results from overproduction of hormones (e.g. aldosterone and cortisol), there
is hyperplasia
 Adrenal glands are triangular glands on top of the kidneys, and if there is a problem in the adrenal glands (e.g. it is
undergoing hyperplasia), then usually it would result to ↑aldosterone production, and in adrenal hyperplasia if aldosterone
production is increased, Na will also be ↑ because there will be too much reabsorption of Na (high levels of Na in the
blood)
Cushings syndrome and disease- hypercortisolism (increased level of cortisol produced from the adrenal cortex)
 Cortisol will inhibit the ADH production. Once ADH (or its release) is inhibited because of high cortisol, then water will
not be retained (no water retention), which would result to increased Na in the blood
because of too much water excreted (relative increase of Na)
Hyperaldosteronism (Conn’s disease)- primary hyperaldosteronism
 Characterized by excessive secretion of aldosterone (increased aldosterone level) from
the adrenal glands.
 The elevated levels of aldosterone causse excessive reabsorption of Na (↑Na levels), and
the person will have hypokalemia (↓ K levels/K wasting), because aldosterone excretes K.
 Serum and Urine Electrolyte Patterns in common causes of hypernatremia (Normal renal function)
 Potassium (K+)
o Also known as “kalium”. o Major intracellular cation.
o It is the chief counterbalance of sodium (because Na is more abundant outside of the cell, as compared to K which is more
abundant inside of the cell)
 Only 2% of K circulates in the plasma, and most of the K is found inside the RBCs, that is why even slight hemolysis would
increase the K values (hemolyzed specimen intended for K analysis should not be run).
o It is the single most electrolyte wherein any abnormality is life threatening (referred to as lethal electrolyte)
 Lethal electrolyte- because little changes in the levels of K could result to serious consequences, because K has a major effect on
the contraction of the skeletal muscles, and particularly on the cardiac muscles (the heart may cease to contract)
 Example: If ↑K (hyperkalemia), there will be a ↓resting membrane potential (RMP) of the cell (because of hyperkalemia), it
would result to a ↓net difference between the RMP of the cell and the action potential of the cell. If the net difference is lower
than the normal difference, it results to ↑cell excitability, which results to muscle weakness (hyperkalemia is very lethal to
patients because it can damage the heart muscles)
 Example: If ↓K (hypokalemia), there will be ↑net difference or ↑RMP, so there will be ↓cell excitability, which would result to
paralysis or arrhythmia (hypokalemia is also dangerous for the heart)
o RBC concentration: 105 mmol/L (23x higher than its concentration in the plasma)
o Reference range: 3.5-5.2 mmol/L or 3.5-5.2 mEq/L
o Threshold critical value: 6.5 mmol/L (hyperkalemia); 2.5 mmol/L (hypokalemia)
o Regulation of Potassium
 Filtered at the glomeruli and is mostly reabsorbed (70%-80%) by active and passive transport mechanisms in the proximal
tubules.
 In the ascending Loop of Henle, potassium is reabsorbed together with sodium and chloride by the sodium potassium chloride
transporter.
o Functions
 Regulation of neuromuscular activity (important in regulating heartbeat and muscle contraction)
 Hyperkalemia (↑K)= ↓RMP= ↓net difference between RMP and action potential= ↑muscle excitability→ Muscle weakness
 Hypokalemia (↓K)= ↑RMP= ↑net difference= ↓muscle/cell excitability→ Paralysis or Arrhythmia
 Contraction of the heart (the heart may cease to contract in increased or decreased K)
 Regulates ICF volume and hydrogen ion concentration
 Hypokalemia- K ions are lost from the body, so as a compensation, the Na and H ions move into the cell, so the H ions are
therefore decreased in the ECF, which results to alkalosis
o Specimen Considerations
 Hemolysis of 0.5% RBC can increase K+ levels by 0.5 mmol/L (30% increase in gross hemolysis)
 Important to prevent hemolysis because even a slight hemolysis could increase the values of K.
 Plasma levels are lower (by about 0.1-0.7 mmol/L) as compared to serum levels
 Due to the release of platelets into the serum during clot formation.
 When obtaining serum, the platelets could be released from the cells that would add up to the K values.
 Muscular activities (e.g. exercise and prolonged standing)= ↑10-20%
 Mild to moderate exercise= ↑ by 0.3-1.2 mmol/L
 Vigorous exercises or when patient was requested to clench the fist upon specimen collection= ↑2.3 mmol/L
 Prolonged application of tourniquet (leads to hemoconcentration and ↑K levels)
 Prolonged contact of serum and RBCs (it is very important to separate the serum from RBCs within 30 minutes)
o Clinical Applications
 Hypokalemia (↓blood K levels; most commonly caused by impaired renal function)
 The dangers of hypokalemia are of concern in all patients (especially with cardiovascular disorders), because they could have an
increased risk of arrhythmias (the condition may cause sudden death in certain patients with cardiac disorders)
 Normal value of potassium: 3.5-5.2 mmol/L, but a decreased level of around 3.0-3.4 mmol/L is classified as mild hypokalemia
 Treatment: Oral potassium chloride, intravenous replacement of potassium, and for chronic cases, foods with high
potassium content incorporated in the diet (e.g. nuts, bananas, orange juice, cereals)
 Causes:
1. Insulin overdose- in patients having DM
Insulin will enable the entry of glucose from the bloodstream into the cell (cellular uptake of glucose)
In insulin overdose, there will be excessive cellular uptake of glucose as facilitated by insulin results to large influxes of
potassium into cells, lowering it in serum (K present in the plasma will be lowered)
2. Alkalosis- there is ↓H+ concentration and ↑pH
Red blood cells are excellent buffers, they can exchange potassium for hydrogen ions. Thus in alkalosis, hydrogen ions leave
the red cells to neutralize excess base while K+ ions enter the red cells.
Inside the RBCs, the major cation is K, with several H + ions present. Outside that RBC, several K (much lower as compared
to the red cell level) and H+ ions in the ECF. In alkalosis, since there is ↓H + ions, so as a compensation, the H+ ions from the
RBC will shift towards the outside of the cell, so H + ions (a cation) is lost in the RBCs. As a replacement, the K will be
delivered inside of the RBCs (so the K ions in the ECF is lost, lowering it in the plasma).
3. Vomiting- this results to the depletion of both hydrogen (H+) and potassium (K+) ions from the stomach
Decrease in K levels is usually the cause of potassium loss in the urine.
Cause metabolic alkalosis- there is an increased bicarbonate ion, the body would tend to eliminate the bicarbonate ions from
the kidneys, leading to an increased excretion of bicarbonate ions, which also leads to renal potassium wasting.
4. Renal Tubular Acidosis (RTA)
Hydrogen ions (H+) cannot be excreted into the urine because of the pathologic impermeability of the DCT membrane to it.
 In DCT, both the H+ and K are excreted, in exchange for Na that is reabsorbed (hormone responsible: aldosterone)
 If there is impermeability to H+ ions, these ions cannot be excreted out to the urine
Hydrogen ions build up in the blood, causing acidosis (↓pH in the blood).
Urine is alkaline, because these hydrogen ions are not excreted.
Hypokalemia results from the increased excretion of potassium to compensate for the inability to excrete H+.
 H+ is a (+) ion, so since it is not excreted, K+ (which is also a positive ion) will compensate for its excretion (hypokalemia)
5. Hyperaldosteronism- Increased action of aldosterone in the DCT will excessively reabsorb Na2+, resulting to the excretion of
increased amount of K+.
6. Pseudohypokalemia
Leukocytosis (increased WBC count) can cause falsely decreased K+ levels because K+ is taken up by the WBCs (like active
leukemic cells), if sample is left at room temperature.
 Hyperkalemia (↑blood K levels)
 An abnormal physiological state resulting from high concentrations of potassium
 Main Causes:
1. Reduced aldosterone/aldosterone responsiveness
2. Impaired renal excretion in renal failure (almost always due to this)
3. Reduced distal delivery of sodium
 These elevations in serum potassium will directly stimulate aldosterone release in order to excrete potassium level.
 Hyporeninemic hypoaldosteronism- most common cause of chronic hyperkalemia (↓renin levels, ↓aldosterone levels)
  Administration of potassium- most common cause of hyperkalemia for hospitalized patients
 Usually, the greatest risk is by giving the patient IV potassium replacement
 Whenever hyperkalemia occurs, the treatment must be started whenever the serum potassium reaches the level of <6-6.5
mmol/L, or if the person has changes in its ECG pattern.
 In order to offset the effect of potassium (which lowers the resting membrane potential of the heart), calcium should be given.
 Calcium (Ca2+) will reduce the action potential of the heart, but is just an immediate and short-lived protection to the
myocardial cells against the effect of hyperkalemia.
 Bicarbonate (NaHCO3), Glucose, and Insulin can also be administered to the patient, because these substances shift the
potassium back into the cells (increases the cellular uptake of potassium).
 Loop diuretics can be given to patients in order to remove the potassium out of the body.
 Top Causes:
1. Hypoaldosteronism- decreased excretion of potassium resulting to increased serum level (e.g. Addison’s disease)
2. Acidosis- hydrogen ions enter the cell in exchange for potassium ions.
Usually ↑H+ and H+ ions will enter the cell in order to balance the blood pH. As exchange to that, the K + will move out of the
cell (K+ will be increased in the ECF in cases of acidosis)
3. Cellular injury
Any kind of cell damage can cause an increase in potassium level, basically because it is highly found inside the cells (just
little values are in the ECF).
Popular causes are rhabdomyolysis and hemolysis.
4. Artifactual (Pseudohyperkalemia)
Hemolyzed sample Excessive fist clenching
Prolonged tourniquet application Blood stored in ice
High blast counts in leukemias
 The blast may also lyse during standard phlebotomy techniques, releasing the K + (also a cause of hemoconcentration of K+)
Thrombocytosis and severe leukocytosis- can cause increased K+ because the K+ will be released from platelets and WBCs,
especially during blood clotting
Use of EDTA as anticoagulant- EDTA exists as Na2EDTA or K2EDTA; never use this anticoagulant when examining blood
for K+
 Chloride (Cl-)
o Major extracellular anion.
o It is the chief counterion of sodium (because outside the cell, the main cation is the Na2+, whereas the main anion is Cl-)
o Works with Na2+ in the maintenance of water balance and osmolality.
 Disorders of Cl- are usually the same with Na2+ (both extracellular ions)
o Has a close relationship with HCO3- in the maintenance of acid-base balance.
o The only anion to serve as an enzyme activator.
o Reference range: 98-107 mmol/L or 98-107 mEq/L
o Heavy hemolysis- decreased Cl- and Na2+ because both will be diluted
o Slight hemolysis- will not affect Cl- and Na2+ (unlike K+)
o Chloride Shift Mechanism
 One of the processes in which the Cl - can maintain electron neutrality aside
from being a rate-limiting component in sodium reabsorption.
1. In this process of cellular respiration, the tissue cells would generate carbon dioxide whenever they receive oxygen.
2. The carbon dioxide generated by cellular metabolism within the tissues will diffuse out into the plasma, and also into the RBCs.
3. Inside the RBCs, the carbon dioxide will also combine with water to form carbonic acid, and with the help of carbonic
anhydrase, the carbonic acid will be split into hydrogen ion (H+) and bicarbonate (NaHCO3)
 Deoxyhemoglobin will buffer the H+ ion released from the carbonic acid
 Bicarbonate ion will diffuse out into the plasma in order to neutralize the excess acid, because of this increased CO 2 release
 Chloride in the ECF will diffuse into the RBC in order to establish electroneutrality.
o Clinical Applications
 Chloride disorders are often a result of the same causes that disturb the Na 2+ levels because
chloride passively follows sodium, however there are few exceptions because hyperchloremia
may also occur when there is an excess loss of bicarbonate (e.g. in GI loses in cases of diarrhea,
renal tubular acidosis, metabolic acidosis).
 Calcium (Ca2+)
o It is present almost exclusively in the plasma.
o 99% is part of the bones and only 1% is in the blood and ECF (very little amount of calcium is found in the plasma).
o Involved in blood coagulation, enzyme activity, excitability of skeletal and cardiac muscles (used in the treatment of hyperkalemia),
and it helps in the maintenance of BP.
o Forms of Calcium
 Ionized (active) calcium (50%)- circulates freely as Ca2+ ions (a sensitive and specific marker for Ca2+ disorders)
 Protein-bound calcium (40%)- Ca2+ is mostly bound to albumin (whenever there is ↓serum albumin, hypocalcemia could follow)
 1 g/dL decrease in albumin= 0.8 mg/dL ↓total calcium (hypocalcemia due to reduced albumin levels in blood)
 Complexed with anions (10%)- usually complexed with bicarbonate, citrate, phosphate, and lactate
o Calcium Regulation
 1,25 Dihydroxycholecalciferol (1,25-(OH)2-D3/active Vitamin D3)- ↑blood calcium level (hypercalcemic)
 It increases the intestinal absorption of calcium.
 It increases the reabsorption of calcium in the kidneys.
 It increases the mobilization of calcium from the bones (it activates the process of bone resorption).
 Parathyroid hormone (PTH)- ↑blood calcium level (hypercalcemic)
 It conserves calcium also by increasing reabsorption in the kidneys
 It increases the level by mobilizing bone calcium
 It activates the process of bone resorption (in which the level of Ca2+ is being increased through mobilization from the bone)
 It suppresses urinary loss of calcium
 It stimulates the conversion of inactive Vitamin D to active Vitamin D3 in the kidneys
 Calcitonin- ↓blood calcium level (hypocalcemic)
 Hypocalcemic hormone  Inhibits PTH and Vitamin D3
 Secreted by the parafollicular C cells of the thyroid gland  Inhibits bone resorption
 Promotes urinary excretion of calcium (does not reabsorb calcium).
o Hormonal Response to Hypercalcemia and Hypocalcemia
 The PTH secretion is stimulated by hypocalcemia, whereas PTH is not secreted in
hypercalcemia.
 PTH has major effects on the kidneys and bones
 Bone- stimulate bone resorption, so there will be osteoclastic activity in which the
osteoclasts will break down the bone (resulting to increase Ca2+ level in the ECF)
 Kidneys
 PTH can conserve Ca2+ by increasing its tubular absorption
 PTH can stimulate the renal production of Vitamin D
Vitamin D3 obtained from diet or exposure of skin to sunlight is still in its inactive form, and will be converted to 25-
Hydroxycholecalciferol (in the liver), but it is still inactive.
Once it reaches the kidneys, that is where it will have its biologically active form (in the kidneys, the Vitamin D 3 will be
activated) and the active form is called as 1,25 Dihydroxycholecalciferol, and its action is towards the intestine and kidney.
 Intestine- Vitamin D promotes intestinal absorption of calcium (Ca2+) and phosphate (HPO4-)
 Kidneys- Vitamin D promotes renal reabsorption of Ca2+ and HPO4-
o Clinical Applications
 Hypocalcemia (↓blood Ca levels)
 Causes:
1. Alkalosis- causes plasma proteins to have a greater negative charge
Whenever there is alkalosis, there is ↓H+ ion concentration (lesser cations in the plasma)
Protein is more on negative charge, so it will bind more Ca2+ ions (since Ca2+ ions are + charged), decreasing Ca2+ levels.
2. Vitamin D deficiency
3. Primary hypoparathyroidism- decreased level of parathyroid hormone secretion
Also in this case, the kidney could excrete more calcium levels out of the blood.
4. Acute pancreatitis 6. Malabsorption syndrome
5. Hypomagnesemia 7. Renal tubular failure
 Hypercalcemia (↑blood Ca levels)
 Causes:
1. Primary hyperparathyroidism- main cause, in which a lot of tumors could produce PTH-like substances that could bind to
normal PTH receptors, and can cause increased calcium levels
2. Cancers (lung and mammary) 6. Sarcoidosis
3. Acidosis 7. Hyperthyroidism
4. Increased Vitamin D 8. Milk-alkali syndrome
5. Multiple myeloma
 Phosphate (PO43-)
o It is omnipresent in its distribution; because 85% in the bones and 15% in the ECF in the form of inorganic phosphate.
o Inversely related to calcium, because of the action of the parathyroid gland
o Reference range: 2.7-4.5 mg/dL (adults); 4.5-5.5 mg/dL (child)
o Inorganic phosphorus exists as:
 Organic phosphate- principal anion within the cell
 Inorganic phosphate- part of the blood buffer; most phosphate in serum is in inorganic form
o Factors affecting Phosphate concentration
1. PTH- decreased phosphate by renal excretion
 Because of its action, Ca2+ and PO43- is inversely related (↑Ca2+,
↓PO43-)
 GI tract- increased absorption of both calcium and phosphate, as stimulated by the release of
PTH
  Kidneys- increased reabsorption of calcium; increased excretion of phosphate
 Calcium and phosphate have an inverse relationship because the PTH could trigger the reabsorption of calcium, but the
phosphate is excreted.
 Bones- increased bone resorption, wherein calcium and phosphate leak into the plasma
 In the stimulation of the bones, the PTH could increase the calcium and phosphate levels
2. Calcitonin- inhibits bone resorption (↓Ca2+, ↓PO43-)
 GI tract- decreased absorption of calcium and phosphate
 Kidneys- decreased reabsorption of calcium and phosphate
 Bones- inhibits bone resorption, promote the shift of calcium and phosphate into the bones
3. Growth hormone- increased renal absorption of phosphate
4. Active Vitamin D3- (↑Ca2+, ↑PO43-)
 GI tract- increased absorption of calcium and phosphate
 Kidneys- increased reabsorption of calcium and phosphate
 Bones- increased bone resorption, wherein calcium and phosphate leak into the plasma
o Phosphate (PO43-) deficiency can lead to ATP depletion.
o Transcellular shift is a major cause of hypophosphatemia- an increased shift of phosphate into cells can deplete phosphate in the
blood, and once it is taken up by the cells, it remains there to be used in the synthesis of phosphorylated compounds
o The equilibrium between serum phosphatases and intracellular phosphate stores is determined
largely by carbohydrate metabolism and blood pH.
o In renal disease, where tubular failure occurs, phosphate excretion is inhibited by the no
responsiveness of the tubules to PTH- phosphate levels rise, while calcium levels fall (↑PO43-,
↓Ca2+)
o Increased serum phosphate causes serum tubular failure.
o Severe hypophosphatemia will result to plasma concentration of <1.0 g/dL or 0.3 mmol/L
 Magnesium (Mg2+)
o Second most abundant intracellular cation (although only 1%, 2nd to potassium).
o The 4th most abundant cation in the body; an enzyme activator.
o Majority is stored in the bones- 53% in bones; 46% in muscles and soft tissues; 1% in serum and RBC
o Reference range: 1.2-2.1 mmol/L or 1.2-2.1 mEq/L
o It is a vasodilator and cause decreased uterine hyperactivity in eclampsic states and increased uterine blood flow.
o Life-threatening symptoms occur if the serum level reaches 5 mmol/L
o Magnesium loss leads to a decreased intracellular K levels (Mg2+ regulates the movement of K+ across the myocardium)
o Factors affecting Magnesium levels in blood
1. PTH
 It increases renal absorption of magnesium.
 It increases intestinal absorption of magnesium.
2. Aldosterone and Thyroxine
 It increases renal excretion of magnesium (lowers the magnesium level in the blood)
 Bicarbonate (HCO3-)
o Second most abundant anion in the ECF (2nd to chloride).
o Accounts for 90% of the total CO2 at physiologic pH
o Buffers excess hydrogen ion by combining with acid.
o Major component of the buffering system in the blood (very important in the regulation of
the acid-base status of the patient).
o Reference range: 21-28 mmol/L or 21-28 mEq/L