ELECTROLYTES

Solutes that affect plasma osmolality

These are ions capable of carrying an electric charge
Fluid (ECF and ICF) always contain equal numbers of cations and anions (to maintain electroneutrality)
40 75% is the average water content of the human body
Total body water: (1) Extracellular fluid (2) intracellular fluid (more water compared to ECF)
o Sodium major cation; abundant in ECF; chloride (major anion)
o Potassium major cation; abundant in ICF ; magnesium (second abundant)
Normal plasma is composed of 93% water and 7% solutes (glucose, proteins, NPN, AA and ions)
Aging and obesity causes body water volume to decrease
Water content of plasma is 12% higher than that of whole blood
Retention of 3 liters of fluid in the tissues will result to edema (pregnant women, patients with renal Diseases)
Deficiency of vasopressin (ADH) causes 10-20 liters of water excreted daily
Sweat contains about 50 mmol/L of sodium (extracellular) and 5 mmol/L potassium (intracellular; increases
during cell lysis)
1500 mL normal volume of water excreted of a healthy individual
Mannitol high molecular weight substance that absorbs water; increased plasma osmolality

Open notes: ELECTROLYTES

ELECTROLYTES
fluids where these anions and cations are found need to have equal number of charges to maintain
ELECTRONEUTRALITY
in the body the fluid where these electrolytes are suspended would be the total body water that comprises the
ECF and ICF

Refer to 2nd page of the chapter on electrolytes

Total body water is distributed into ICF and ECF.

Total body water is about 42 L,
28L are considered to be ICF
14L are ECF, which is further divided into
o Interstitial fluid
o Plasma
The concentration of the electrolytes that are suspended in the total body water is greatly affected by water intake and
water output
Daily we lose about 1500mL of water through the:
Kidneys
Skin
Lungs
Gut
That would be mean that there could be a change in the concentration of the solute, specifically the electrolytes in the
plasma
- Loss of water has to be compensated, so that we maintain the normal concentration or amount of electrolytes that
are distributed in the total body water

Water that is lost maybe compensated by water that is taken in the body through
Diet that is why we are required to take a minimum if 8 glasses daily
Water released by Oxidative metabolism of cells remaining amount provided by the body
In that way we are able to compensate for the 1500mL of water that we lose daily through the
Sweat
Urine
Respiration
Between the ICF and EC, its the ECF that we are concerned about because it is where we obtain our samples, esp
through
Venipuncture
Capillary puncture

The solutes that we can measure in the laboratory mostly comprises of:
o 92% of plasma osmolality - Sodium
o 8% - would come from the other solutes [glucose, urea-most abundant NPN substance, protein]
o Protein, although circulating in the plasma, has less concentration than glucoe, because it doesnt stay
long in thye plasma, since most of the protein that are synthesized in the liver are also also in order to
maintain nitrogen balance in the body
o Albumin, that is synthesized in the liver would ususally find their weway to the interstitial fluid to
maintain ONCOTIC PRESSURE between the tissues and the plasma

Concentration of the ECF that would greatly affect the suspended electrolytes in the plasma
o There are two important properties of the ECF
OSMOLALITY
VOLUME

OSMOLALITY concentration of solute suspended in the solvent (concentration of sodium, glucose, urea
and protein that are found in the plasma)

- Any change of the ratio of the solute to the solvent would greatly affect the osmolality. Such that,
- if there is loss of water and is not compensated, the plasma osmolality is higher/increased because more
solutes are suspended in the solvent due to water loss
- if more water is taken in the body, Overhydration, there will be solvent, the solute suspended in it are
considered lesser plasma osmolality is lower

*aside from intake of water and production of water through the cells, the body normally responds to changes
in osmolality, especially if there is water loss.

When water is lost by the body, automatically there would be a change in the osmolality, and the change in
osmolality will immediately send signals to the hypothalamus, and hypothalamus will activate hypothalamic
thirst center.

Hypothalamus activates
Change in plasma osmolality Send signals to hypothalamus
HYPOTHALAMIC THIRST CENTER

- That is why when the water is lost, the body will immediately feel thirsty
Not only that..
- The hypothalamus automatically synthesizes the hormone ADH/Vasopressin
- ADH , once synthesized will be stored in the posterior pituitary gland
- And when there is changes in plasma osmolality (esp when it increases)
- The posterior pituitary gland will secret ADH
- The ADH secreted will be carried by the circulation to the target cells (DCT)
- The hormone ADH will attach to plasma receptor of the DCT
- The attachment of the hormone to the receptor in the DCT cells will activate 2nd messengers specifically
cAMP (cyclic adenosine monophosphate)
 - Its the 2nd messenger, cAMP, that will send the hormone-receptor complex signals to the nucleus of the
cells of the DCT
- Since the nucleus is the brain of the cell, it will respond to the hormone-receptor complex carried by the 2nd
messenger
- The cells will produce aquaporins in the plasma membrane
- The aquaporins will be a way by which water will be reabsorbed back to the plasma in order to maintain
plasma osmolality

Water loss -> CHANGE cAMP sends hormone-

activation of 2nd
in PLASMA receptor complex to
messanger (cAMP)
OSMOLALITY the nucleus of the cells

send signals to Nucleus responds by

HYPOTHALAMUS ADH/Vasopressin
producing
attach to plasma
-synthesis of AQUAPORINS in the
receptoon DCT cells
ADH/Vasopressin plasma membrane

POSTERIOR PITUITARY
GLAND AQUAPORINS
ADH/Vasopressin in
-secretes reabosorb water back
the circulation
ADH/Vasopressin to plasma
stored
=This is how the normal healthy individual would normally respond to changes in plasma osmolality specifically
if there is an increase in plasma osmolality

On the other hand, if the plasma osmolality decreases, it would be very easy to return plasma osmolality to
normal because the only way by which we can return it normal is to eliminate the excess water
- ADH will not be secreted
- However, it will initiate elimination of excess water

As you can see of page 134, you will see the conditions that are associated with plasma osmolality increase
would usually be due to loss of water. The most common cause of increase in plasma osmolality is
excessive loss of water like dehydration
Addition of solutes like metabolites of alcohol or any any alcoholic products could increase plasma
osmolality
Increase in electrolytes like Calcium increase osmolality
Deficiency in ADH, Diabetes Insipidus will increase plasma osmolality bc ADH will not be secreted.
o If ADH will not be secreted by the Posterior Pituitary Gland -> water will not be reabsorbed -> most
water will be eliminated-> plasma osmolality will remain elevated
Individuals who are taking X-ray dyes and Mannitol
o Substances that have large molecular weights, if they are seen in the plasma
o These molecules will absorb water
o If they water is absorbed by these molecules, then
o Less amount of solvents are seen circulating in the plasma
o Causing a increase in osmolality

On the other hand ..

Conditions that are associated with decrease in Plasma Osmolality would be due to excess water in the plasma
Most common cause would be secretion of inappropriate amount of ADH
This would be due to inappropriate secretion of ADH by the posterior pituitary gland
Even if plasma osmolality is normal, if the DCT continues to reabsorb water bc of secretion of ADH,
then more water will be seen circulating in the plasma
causing decrease in plasma osmolality
Another important property of ECF is Extracellular Volume
If osmolality changes, due to intake of water

VOLUME
- when we talk about Volume, we are referring to the amount of solutes that are suspended in the plasma
that could affect osmolality

Since the most abundant solute in the plasma is sodium

It is the concentration of sodium that could markedly affect colume
Increase sodium that could affect volume, it would in turn affect osmolality
The body also responds to changes in sodium concentration
Hormones play an important role in these changes..

When sodium levels are low,

- Macula densa cells of the kidneys, automatically release renin
- Renin is converted into an active enzyme/growth hormone, angiotensinogen
- Prohormone Angiotensinogen is converted into to the active hormone which is Angiotensin 1
- Angiotensin 1 formed in the kidney cells is immediately secreted into the circulation ( it has to be
released to the circulation to reach the lungs)
- Angiotensin reaches lungs
- It is only in the lungs where ACE converts angiotensin 1 to angiotensin 2)
- Angiotensin 2 hormone secreted by the lungs is carried by the circulation
- It will attach to receptors of the adrenal cortex
- Hormone-receptor complex in the adrenal cortex activates the adrenocortical cells
- Adrenocortical cells secrete the hormone aldosterone
- Aldosterone secreted by the Adrenal cortex has its receptors in the DCT cells
- Attachment of aldosterone to the receptors of the DCT cells
- DCT cells will respond by reabsorbing sodium
Sodium levels are Angiotensin 2 attach
low Hormone-recpetor
to receptors of the
complex activates
->MACULA DENSA cells in the adrenal
adrenocortica l cells
releases RENIN cortex

Angiotensin2 from
Renin -> Adrenal cells
lungs released to
Angiotensinogen secrete Aldosterone
the circulation

Aldoesterone
ACE converts
Angiotensinogen -> attaches to
Angiotensin 1 to
Angiotensin 1 receptors of DCT
angiotensin 2
cells

Angiotensin 1
Angiotensin 1 DCT will reabsorb
released into the
reaches the lungs sodium
circulation

=That would respond to the decrease sodium levels

Several hormones play an important role in maintaining sodium levels (very low sodium levels)

When sodium levels are very high,

- The cardiac cells secrete Atrial Natriuretic Factor/Peptide (ANF)
- Once ANF is secreted
- ANF inhibits aldosterone secretion
- ANF also inhibits the release of renin
 - When renin and aldosterone are inhibited, sodium will not be reabsorbed by the DCT
- It will not absorb bc the sodium levels are very high
Sodium level is Renin and
low aldosterone
inhibition

Sodiumnot
Cardiac cells
reabsorbed by
secrete ANF
the DCT

ANF inhibit
Sodium level
renin and renin
high
secretion

There has to be a mechanism to eliminate the excess sodium

(gnstop mo gd man ang reabsorption, but there should be a mechanism to eliminate the excess sodium in the
plasma
That will only happen if the ANF will act on the PCT
stopping reabosption of sodium
stopping the exchange in electrolytes in the Loop of Henle
Sodium will not be reabsorbed in exchange for Potassium
Sodium will be eliminated directly through the urine

Main action of ANF

Natriuresis eliminate excess sodium by preventing sodium reabsorption

There are 2 conditions that can greatly affect OSMOLALITY and VOLUME
Loss of water
Water intake

Loss of water
- Will not only affect osmolality bc the loss of water can be accompanied by loss of sodium
o If this happens, Osmolality will not only one affected but this will also affect ECF Volume
- So the plasma osmolality will vary on what is lost
o Only Loss of water, or
o Loss of water accompanied by Loss of Sodium

Water content is 12% higher than that of Whole blood

- whole blood contains RBC
Retention of 3L of fluid in the tissues will result to EDEMA
- water will not only stay in the plasma , it will its way to the Interstitial Fluis
Deficiency in ADH causes 10-20L of water excreted daily
- bc ADH is responsible for water reabsorption
- patient suffer extreme dehydration unless the patient is given continuous water intake through mouth or IV
Sweat contains about 50mmol/L of sodium and 5mmol/L of potassium
- less concn of potassium than sodium
- Why?
o (Intracellular) Most Potassium is found in the cells

Functions (very essential in the normal functioning of several cells)

For volume and osmotic regulation (Na, Cl, K)
For myocardial rhythm and contractility (K, Mg, Ca)
Important cofactor and enzyme activation (Ca, Mg, Zn) ; found in the ICF
o Proper linkage between the enzyme and substrate acting as activators
For the regulation of ATPase ion pumps (Mg)
 For neuromuscular excitability (K, Mg, Ca)
For the production and use of ATP from glucose (Mg, PO4)
Maintenance of acid base balance ; buffers (PO4, HCO3, K, Cl)
o Most anions play an important role as buffers not only in the ICF but also the ECF
Replication of DNA and the translation of mRNA (PO4)

SODIUM
Natrium ; 92% of the dissolved solutes in the plasma
Major extracellular cation
Major contributor of plasma osmolality (ECF is half of the total body water)
The principal osmotic particle outside the cell
Its plasma concentration depends greatly on the intake and excretion of water
o How is sodium /levels affected by water intake?
Sodium levels will be decreased
o How will it affect osmolality?
Osmolality will also be decreased
------------------------------------------------------------------------------------------------------------------------
o How is elimination of water affect sodium concentrations in the plasma?
Sodium concentration increases
o How will that affect osmolality?
Increase osmolality
As you can see, though volume will be mainly affected by sodium concentration, it will in turn affect osmolality

However, we dont only need serum/plasma samples to asses sodium abnormalities,

Collect urine samples
o To measure urine sodium and urine osmolality
o Esp. if patient is restricted with fluids
o
*Right side and left side of the room tukso-tukso by maam*

How does fluid restriction affect serum/plasma osmolality and how will it turn affect urine osmolality?
If fluid is restricted
o Plasma osmolality will be increased
o Urine osmolality will be increased
How?
- ADH regulation (ara sa babaw lol)
Why is urine osmolality increased?
- Because water is reabsorbed

All confirmed serum sodium abnormalities must be followed up with urinalysis including urine sodium and
urine osmolality on the patient, who should be on fluid restricted diet
Reference value: 135-145 mmol/L
Threshold critical value: 160 mmol/L (hypernatremia ; secretion of ADH and atrial natriutretic peptide) 120
mmol/L (hyponatremia ; secretion of aldosterone)
CSF sodium: 136 150 mmol/L
o Very little difference in the plasma sodium concentrations

Most commonly quantitated electrolyte in the plasma

Hormones Affecting Sodium Levels

Aldosterone
promotes absorption of sodium in the distal tubule
Promotes sodium retention and potassium excretion (maintaining electrical neutrality)
When is aldosterone secreted?
- When sodium levels are decreased
- Secreted by adrenal gland specifically adrenal cortex
Atrial Natriuretic Factor (ANF)
Maintain normal excretion of excess Na in the urine
It is an endogenous antihypertensive agent (prevents increased blood pressure) secreted from the cardiac atria
It blocks aldosterone and renin secretion and inhibits the action of angiotensin II and vasopressin
It causes natriuresis

When is ANF secreted?

- When sodium kevels are increased
- Inhibit secretion of renin and aldosterone
- Promote natriuresis

PAGE 136
Table is shows the cations and anions in the ECF and ICF
Sodium is most abundant in the plasma , abundant in the ICF
There are also other cations like Calcium and Magnesium that are distributed in the plasma

Chloride- most abundant anion in the plasma

- Cl attracted to Na bc they are opposite in charge
- They exist as salt in the plasma
That is why there is exchange in sdium and potassium between the cells and the plasma
If sodium enters the cell, usualy accompanied by Cl

Bicarbonate is also found in the plasma

- Acts as a buffer
- Not that high in concentration because it usually enters the RBC in thelungs combining with Hydrogen Ions to
form carbonic acid that will rapidly breakdown into CO2 and H2O
- CO2 will be eliminated by the lungs through respiration
- Important buffer in the plasma

Phosphate
Abundant in the ICF because it acts as intracellular buffer

Computation of most abundant and cations in the plasma

is essential to arrive at the anion gap
Anion Gap
- would tell you the distribution of the anion and cations in the total body water is normal
- (refer to book please)
- Subtracting the sum of the anions with that of the cations
- Only get the concentration of the chloride & bicarbonate and sodium & potassium
- Reference range will vary depending on the cations that will be measured

If its only sodium that is measured

o Ref value: 7-14mmol/L
If potassium will also be measured
o Add concentration potassium and sodium and subtract chloride and bicarbonate concentration from the
sum of the K and Na
o Ref value: 10-18mmol/L
Increased Anion gap:
Similarity: Increased plasma Osmolality
Decreased Anion gap:
Decreased plasma osmolality
Multiple Myeloma decreased Ig
Protein error decreased synthesis of proteins
No QC of the instrument

Conditions affecting ECF osmolality: Hypernatremia and Hyponatremia

HYPERNATREMIA
Iatrogenic increased Na levels post operation, because of treatment or medications
Increased sodium concentration of plasma water
Generally diagnosed at serum sodium levels >145 mmol/L
Caused by loss of water, gain of sodium, or both
It usually results from excessive water loss
Perspiration and breathing would result to one liter of water loss/day in adults
A water deficit of 1-2% leads to severe thirst
Serum levels of 150-160 mEq/L is indicative of moderate deficit of water; >165 mEq/L is severe water deficit
With rapid intake of water, venous sodium concentration will be about 4 mmol/L higher than that of arterial
blood
o Rationale: water intake immediately promotes diuresis
o Dasig intake, dasig loss of water
o Sipping of water most water will be retained by the body
o Depend on plasma osmolality
o Plasma osmolality is decreased, you want water to be retained, take water slowly
o If you want water to be eliminated-rapid drinking
Drinking 20 mL/kg of water in 15 minutes reduces arterial sodium by about 8 mmol/L and results in rapid water
diuresis, but the same amount given by slow sipping does not produce water dieresis
Chronic hypernatremia in an alert patient is indicative of hypothalamic disease (possible defect in hypothalamic
thirst center responsiveness)

Conditions associated with increased sodium levels due to 3 causes:

1.) Excess water loss

- diabetes insipidus (incapability of secreting ADH- H20 not reabsorbed)
- renal tubular disorder (- H20 not reabsorbed in the PCT and DCT)
- prolonged diarrhea (H20 is eliminated)
- profuse sweating (H20 is eliminated)
- severe burns (H20 is eliminated-wala sng skin that prevent water loss) ( water and albumin are lost gatapik ang gauze)
- vomiting (H20 is eliminated)
- fever (high temp)
- hyperventilation (water loss bc of respiration)
Osmolality increases

2.) Increased intake or retention of sodium

3.) Decreased water intake

- hyperaldosteronism (Cohns disease) adrenal cortex secretes aldosterone regardless of the Na levels (sodium
reabsorbed)
Defect in adrenal gland
- sodium bicarbonate infusion
Increased intake through IV
- increased oral or IV intake of NaCl
Increased intake through IV
-ingestion of sea water
Increased intake
Sea water is high in sodium die bc of increased plasma osmolality =HYPERVOLEMIA
-decreased water intake

HYPONATREMIA

1.) increased sodium loss

- diuretic use
Pagwa nya
Promotes diuresis
Loss of water and sodium
- saline infusion

Volume is mainly affected

Sodium is lost abi
Inturn affect osmolality

2.) Increased water retention

- renal failure (failure to concentrate urine)
- nephritc syndrome
- aldosterone deficiency
- Cancer ( Ectopic secretion of ADH)
- SIADH (oversecretion of ADH)
- hepatic cirrhosis
- Primary polydypsia
Osmolality is affected
o How? decrease plasma osmolality
That will in turn affect sodium concentration

HYPONATREMIA
Reduced plasma sodium concentration to a value less than 135 mmol/L
If renal failure occurs, the kidneys ultimately fail to concentrate the urine resulting to hyponatremia
o What part of nephron/Kidney?
DCT fine tuning prior to eliminating
Loop of Henle
Collecting duct
If urine sodium is more than 20 mmol/day, there is ongoing renal loss of sodium and water
For every 100 mg/dL increase in blood glucose, serum sodium decreases by 1.6 mmol/L
o Rationale: dependent on Potassium concentration
o Why? potassium will only enter the cell in the presence of insulin
Potassium intake of cells is dependent on insulin
Diabetics (esp DM1) absolute deficiency in Insulin
Postassium increases in plasma
Sodium decrease in plasma
Accumulation of glucose or mannitol in the ECF (transfer of fluid from ICF) is a well-known cause of
hyponatremia
o Why? Because plasma and mannitol are large mol weight substances
 o Osmotically active water from the ICF will diffuse to the ECF -> diluting electrolytes
In diabetes mellitus, sodium loss occurs with ketonuria
o Ketones will also be eliminated through the urine
o Why? -In DM1 excess ketone bodies bc it is the source of energy of the cells
Decreased serum sodium in SIADH is due to excess retention of water in the collecting ducts
o Hypothamus defect increased synthesis of ADH even if Plasma Osmo is normal
o Posterior Pituitary gland defect increase secretion of ADH even if Plasma Osmo is normal
o Reabsorb water, decrease plasma osmo, dilute solutes
Potassium deficiency in ICF (insulin deficiency ; K cannot enter the cells) causes loss of sodium
o Kulang si potassium sa plasma, hawiran sng body si potassium to maintain normal levels
o So kung hawiran , No elimination of potassium, sodium is eliminated instead
In Bartters syndrome (mutation in basolateral chloride channel [sodium, chloride, potassium co-transpoter] this
is the co-transporter medium that will allow reabsorption of sodium in the kidneys. If this co-transport is not
present, all other electrolytes will not be reabsorbed.
o hyponatremia is not corrected with fluid restriction, patient will still have hyponatremia even if fluid is
withheld
o In normal people, doctor will restrict patient fluid intake to make levels of Sodium back to normal
There is loss of theexcess water -> hypo will return back to normal
Symptoms of hyponatremia occurs if the serum level is 125-130 mmol/L
Serum sodium level of <125 mmol/L may result to severe neuropsychiatric symptoms (decreased neuromuscular
excitability)
By examining the urinary sodium, potassium and osmolarity, the causes of hyponatremia and hypernatremia can
be readily determined

PSEUDOHYPONATREMIA (false decrease in sodium)

Reduction in serum sodium concentration caused by a systematic error in measurement
Most common cause is in vitro hemolysis ( a well known cause off pseudohyperkalemia)
Marked hemolysis may cause decreased sodium levels (increased K levels) due to dilutional effect
Artifactual hyponatremia is also associated with hyperlipidemia or hypoproteinemia
Cause:
o Langka (daw) ang Med Tech (AHAHAHAHAHAHAHA)
May also be a side effect to the person with hyperlipidemia/hyerlipoproteinemia

If you are in doubt of whether the sodium levels are truly the that:
DELTA Check previous result
Interview

HYPONATREMIA with NORMAL RENAL FUNCTION

Cause Serum Na Urine Na 24-hour Na Urine Serum K

osmolality
Overhydration Low Low Low Low Norma or Low
Diuretics Low Low High Low Low
SIADH Low High High High Normal or Low
(increased
water
retention)
Adrenal Failure Mildly elevated Normal High High
Bartters Low Low High Low Low
Diabetic Low Normal Normal Normal High
hyperosmolality
METHODS
EFP (Emission Flame Photometry)
o Principle:
Qualitative EFP: The concentration of sodium is directly proportional to the intensity of the color
of the flame (Qualitative EFP)
Sodium color yellow
Quantitative EFP: The concentration of the sodium is directly proportional to the emitted light
intensity of the atoms from the excited state to the ground state (kung manug naog na
maproduce photon)
Disadv: TEMP of the flame (multiple stoms are excited), COEXCITATION
ISE (Glass aluminum Silicate) entry of sodiums only ; most commonly used method ; potentiometry
o Is the electrode similar in structure to the pH electrode or pCO2?
o Yes. pH electrode gn butangan lang sng membrane->pCO2
o Preho man for sodium
o Daw si pH lang pero lainay lang sila membrane ni pCO2
o Teflon-membrane for pCO2
o Sa ISE-glass aluminum silicate - measure sodium ions- allowing entry of sodium ions only and not other
cations
AAS most preferred mthod for measurement of sodium
o concentration of the electrolyte is proportional to light absorbed in neutral ground state
o Hollow cathode lamp light source specific to sodium measured
Colorimetry (Albanese Lein)
o Reagents: Zinc Uranyl Acetate
o Product: Sodium uranyl acetate ppt
o Visible: yellow solution

POTASSIUM
Kalium
Major intracellular cation
Only 20% of the bodys total potassium circulates in plasma
The concentration in the RBCs is 105 mmol/L (23x higher than its concentration in plasma)
It is filtered at the glomeruli and is mostly (70-80%) reabsorbed by active and passive mechanisms in the PCT
In the ascending limb of the loop of Henle, K+ is reabsorbed together with Na+ and Cl- (basolateral chloride
channel) by the sodium potassium chloride cotransporter
The single most important analyte in terms of an abnormality being immediately life threatening
Functions: heart contraction, neuromuscular excitability, ICF, volume regulation and hydrogen ion concentration
Reference Value: 3.5 5.2 mmol/L (plasma)
Threshold critical value: 6.5 mmol/L (hyperkalemia) 2.5 mmol/L (hypokalemia)

Specimen considerations
Hemolysis of 0.5% RBC can increase levels by 0.5 mmol/L (30% increase in gross hemolysis)
Plasma levels are lower (0.1 0.7 mmol/L) compare to serum levels because of the release of platelets into the
serum during clot formation
Muscular activity like exercise and prolonged standing 10 to 20% increase (0.3 1.2 mmol/L inc in mild to
moderate exercise and 2.3 mmol/L inc in vigorous exercise and fist clenching)
Prolonged contact of serum and red cell
Prolonged application of tourniquet

HYPERKALEMIA

Decreased renal excretion

 Acute or chronic renal failure
Severe dehydration
Addisons disease
Increased intake
Oral or IV infusion
Extracellular shift
Acidosis (inc H+ ion concentration, eliminated instead of potassium ; H+ ions and potassium cannot be
eliminated together because of similarity in charges; K is retained)
Muscle/cellular injury
Chemotherapy
Vigorous exercise
Digitalis intoxication
Use of immuonosuppresive drugs
Tacrolimus and Cyclosporin
HYPOKALEMIA

Gastrointestinal Loss
Gastric suction and laxative abuse
Intestinal tumor and malabsorption
Cancer and radiotherapy
Vomiting and diarrhea
Intracellular shift
Alkalosis
Insulin overdose
Renal Loss
Use of diuretics (thiazides)
Hyperaldosteronism (increased sodium)
Cushing syndrome
Leukemia
Bartters Syndrome
Gitelmans Syndrome
Liddles syndrome
Malignant hypertension

HYPERKALEMIA
Always due to impaired renal excretion
Elevations in serum K+ can directly stimulate the adrenal cortex to release aldosterone (increased Na ;
decreased K)
3 major mechanisms of diminished renal K+ excretion
o Reduced aldosterone or aldosterone responsiveness due hyporeninemic hypoaldosteronism ; macula
densa cells cannot secrete renin (decreased Na ; increased K)
o Renal failure
o Reduced distal delivery of Na

Renal Failure
Reduced GFR and decreased tubular secretion causes accumulation of potassium including magnesium and
phosphorus in the plasma

Effects to cardiac muscle

Hyperkalemia decreases the resting membrane potential (mV) of the cell
Severe hyperkalemia can ultimately cause a lack of muscle excitability (8 mmol/L)
Plasma K+ levels of 6-7 mmol/Lmay alter ECG
 Plasma K+ levels of 10 mmol/L is fatal ( cardiac arrest)

pH imbalance ( acidosis) and Drugs

In acidosis, plasma K+ increases by 0.2 1.7 mmol/L for each unit reduction of pH (H+ enters the RBC and as an
exchange, K+ moves out of the cells)
Low insulin levels cause high serum potassium
Therapeutic K+ administration
Hyperkalemic drugs captopril, spironolactone (K+ sparing-diuretic), digoxin, cyclosporine and heparin therapy
Digitalis inhibits the Na+-K+-ATPase pump
PSEUDOHYPERKALEMIA
Sample hemolysis
Thrombocytosis
Prolonged tourniquet application
Fist clenching
Blood stored in ice
IV fluid
High blast counts in acute or accelerated phase leukemias (blast may lyse during standard phlebotomy releasing
K+)
Thrombocytosis and severe leukocytosis cause potassium release from the platelets and white blood cells
during blood clotting
Recentrifugation of SST (Serum Separator Tube)
Electrocardiographic (ECG) abnormalities of hyperkalemia are absent in pseudohyperkalemia, but the absence of
ECG changes does not rule out true hyperkalemia because ECG changes are rare in chronic hyperkalemia

HYPOKALEMIA
Plasma K+ levels of 3.0 3.4 mmol/L is mild hypokalemia
Hypomagnesemia (magnesium acts enzyme activator) leads to hypokalemia by promoting urinary loss of
potassium
If plasma K+ levels are low, it will be retained and NH4+ ions will be secreted if balancing cations are needed
Extra Renal Loss
Diarrhea
Vomiting (alkalosis)
Urine

EFFECTS TO CARDIAC MUSCLE

Hypokalemia decreases cell excitability by increasing RMP (increased K+ inside the cell), resulting in arrhythmia
and paralysis
The heart may experience cessation of contraction in either hyperkalemia or hypokalemia
Heart failure does not lead to hypokalemia despite secondary hyperaldosteronism, unless distal delivery of Na+
is increased by diuretic therapy

pH IMBALANCE (ALKALOSIS) AND HORMONES

In alkalosis, plasma K+ decreases by 0.4 mmol/L/0.1 pH unit rise
pH balance due to increased concentration of bicarbonate and pCO2 leads to movement of K+ into the cells
direct stimulation of aldosterone secretion by metabolic acidosis
insulin and catecholamines

PSEUDOHYPOKALEMIA
Leukocytosis can cause falsely decrease potassium levels because K+ is taken up by WBC, like active leukemic
cells, if sample is left at room temperature

METHODS
 EFP (purple or violet flame)
ISE (valinomycin) allow entry of potassium only
AAS
Colorimetry (Lockhead and Purcell) (book)
Type 1 reagent grade water is used for analysis

INORGANIC PHOSPHORUS

It is omnipresent in its distribution

85% in the bones
stored together with calcium to form hydroxyapatite crystals
strengthens bone
15% in the ECF in the form of inorganic phosphate
PTH produces an inverse relationship to calcium
Maximally absorbed in the jejunum
Phosphate is essential for the insulin-mediated entry of glucose into cells by a process involving phosphorylation
of glucose and the co-entry of potassium
Cellular uptake of potassium requires insulin

Why is phosphate needed for glucose entry?

Once glucose enters the cells it undergoes phosphorylation. Glucose in the presence of the enzyme hexokinase,
will convert glucose into glucose-6-phosphate.
Phosphorylation is needed to make sure that the glucose that entered the cell does not go out of the cell and to
ensure that the glucose that entered the cell can provide energy.

Reference values

Child Adult
4.5-5.5 2.2-4.5
mg/dL mg/dL
Higher in children because needed for growth and development of bones.

Organic phosphate- principal anion within cells (bone cells)

Inorganic phosphate- part of the blood buffer

Three forms of phosphorus:

1. Free or unbound - 55%

2. Complexed with ions (ions like Ca) 35%
3. Protein bound (albumin) 10%

Factors affecting phosphate concentration

PTH- when secreted, phosphate levels are decreased by renal excretion

Calcitonin- inhibits *bone resorption (*breakdown of bone tissues to release Ca)
Growth hormone- increases renal reabsorption
Growth hormone will increase phosphate levels if phosphate levels in the plasma are low
PTH and calcitonin will be secreted if phosphate levels in the plasma are too high
Notes to remember when assaying phosphate

Fasting is required
A high carbohydrate diet can result decreased levels
Used by the cells for phosphorylation
Separate the serum from the red cells immediately after clotting is completed
Since its an intracellular anion, hemolysis can release phosphates that can falsely increase the results

Methods (page 145)

Fiske Subbarow method

Reagent: ammonium molybdate, pictol (aminonaphthol sulfonic acid) reducing agent
End product: ammonium-molybdate complex (unstable)
Visible result: blue
Measure @ 700nm
Other reducing agents: elon (methyl amino phenol), ascorbic acid and senidine (N-phenyl-p-phenylene diamine
hydrochloride)
Prepare PFF to remove proteins that can act as interference
The pH must be maintained in the acid range because higher range (alkaline) can result to reduction of the
complex

Daly - Ertingshausen method

Reagent: ammonium molybdate in sulfuric acid
Used to precipitate the proteins: tween 80 (wetting agent)
Visible result: colorless read @ 340nm

Hyperphosphatemia and hyphophosphatemia (page 146)

Rickets- Vitamin D deficiency in children

Osteomalacia- Vitamin D deficiency in adults

Notes to remember:

Phosphorus is measured in the form of phosphate

Usually expressed in mEq/L
Has circadian rhythm
higher in the afternoon compared in the morning
first morning samples are the most appropriate
the amount of phosphate in cells is determined by carbohydrate metabolism
increased CHO intake, decreased phosphate because of phosphorylation
blood pH
acidosis= decreased because it will act as a buffer
In individuals who have renal diseases- renal tubules are affected; the elimination of phosphate will be inhibited.
Phosphate levels will increase, calcium levels will decrease.
If an individual has a increased phosphate, decreased calcium, elevated BUN and creatinine, then it is strongly
suggestive of tubular failure.
Deficiency in phosphate can lead to ATP depletion
Phosphate is needed for the synthesis of ATP
 Transcellular shift (shift of phosphate from the plasma to the cells) is a major cause of hypophosphatemia (can
deplete phosphate in the blood)
Severe hypophosphatemia will result to plasma concentration of <1.0g/dL or 0.3mmol/L

MAGNESIUM

Is an intracellular cation second in abundance to potassium

Is the fourth most abundant cation in the body
An enzyme activator
Majority is stored in the bones- 53% in bones; 46% in muscles and soft tissues; 1% in serum and rbc
It is a vasodilator and cause decreased uterine blood flow
Life threatening symptoms occur if the serum level reach 5 mmol/L
Loss of magnesium will also lead to decreased intracellular potassium levels
Both are found inside the cells. If the cells undergo lysis, potassium decreases, consequently magnesium will also
decrease.

Functions:

Maintains the structure of DNA, RNA, and ribosomes.

Synthesis of CHO, CHON, and lipids
Acts as an activator
Responsible for neuromuscular transmission
Cofactor
Regulates movement of potassium across the myocardium

Reference range: 1.2-2.1 mEq/L

Three forms of magnesium:

1. Free or ionized- 55% (physiologically active)

2. Protein bound magnesium- 30%
3. Complexed with ions- 15%

Factors affecting magnesium concentration:

PTH- increases renal reabsorption of Mg; increases intestinal absorption of Mg (the same function with Ca)
Aldosterone and thyroxin- increases renal excretion of Mg
PTH- Secreted when Mg levels are low
Aldosterone & thyroxin- secreted when Mg levels are high

Hypermagnesemia

Diabetic coma
Addisons disease
Chronic renal failure
Increased intake of antacids, enemas, and cathartics

Hypomagnesemia
 Acute renal failure
Malnutrition
Chronic alcoholism
Severe diarrhea
Malabsorption syndrome (sprue)

Methods (page 146)

Colorimetric methods
Calmagite method
Reagent: naphthol sulfonic acid derivative or calmagite
Polyvinylpyrrolidone- minimize effects of serum proteins
Visible result: reddish - violet complex read @ 520nm

Formazan- dye method colored complex

Magnesium thymol blue method- colored complex
AAS reference method
Dye- Lake method (clayton yellow/ titan yellow/ thiazole yellow)
Visible result: red lake colloidal precipitate

BICARBONATES

Important electrolyte because it is the most important buffer in the blood.

The rbcs are responsible for secreting bicarbonates
In plasma, it maintains blood ph in acidosis by combining with hydrogen ions

Requirements
Collect the sample anaerobically

Method
ISE PCO2 electrode (severine house electrode)

Reference value:
21-28 mEq/L

- Venous blood can be used to obtain plasma/ serum sample

-Bicarbonates have a relationship with chloride

When chloride levels are increased bicarbonate levels are decrease (inversely proportional)

Chloride shift
Process of the shifting or the changes in the chloride

When hco3 ions go out of the rbc tendency is, to maintain electrical neutrality within the rbc, chloride ions are required
to enter. That is why when bicarbonate ions are high in the plasma, chloride levels will be low because there will be a
transfer of chloride ions from the plasma to the red blood cell.

IRON
 It is about 3.5 g of iron in the body
Found in the rbcs

It is important because:
- it is responsible for carrying oxygen in hemoglobin
- it prevents dna damage and carcinogenesis

Transferrin
The carrier of iron in the plasma

Transferrin picks up iron from the reticuloendothelial cells or spleen where rbcs undergo lysis. When rbcs are lysed,
hemoglobins are released.

Haptoglobin
Picks up the hemoglobin from the lysed rbcs and bring it to the RES. Then hb will breakdown into heme and globin.
Globin will be broken down into amino acids that are stored in the liver cells
Heme Some will be taken by hemopexin and bring it to the liver or bone marrow while some will be taken by
transferrin and bring it to the bone marrow or keep it in the spleen or liver

Apoferretin
A substance in the bone marrow, spleen and liver that waits for iron from transferrin.

When apoferretin receives iron, it will be converted to ferretin

Ferritin
The storage form of iron

Hemosiderin
Denatured form of ferritin and it is converted into a pigment

Hemoglobin: 2- 2.5 g
Myoglobin: 130 mg
Tissue: 8mg
Plasma(albumin/free hb): 3-5 mg

- Before iron levels decrease in the plasma, stored ferritin should first be depleted in cells.
- It is possible that the iron is normal but the ferritin in low. It means transferrin is defective. Transferrin may not be able
to carry iron.

Reference value:
Male: 50-160 ug/dl
Female: 45 150 ug/dl

Females have lesser value because they lose

Increased iron levels

Pernicious (ineffective of decreased erythrocyte)
Hemolytic anemia (increased hemolysis)
Lead poisoning or pyridoxine deficiency (cannot synthesize heme)
Increased iron intake
Decreased iron levels
Decreased intake of iron
Accelerated loss of iron
Acute blood loss or late pregnancy
Infection
Neoplasia
Rheumatoid arthritis
Acute hepatic cell necrosis (iron is not stored in the liver therefore it cannot synthesize heme and cannot
produce hemoglobin)

Methods (page 148)

A. Colorimetry
HCl and ferrozine blue color
Reagent: Thioglycolic acid
8
- proteins are precipitated
- Conversion of ferric to ferrous so that all the iron bound to transferrin will dissociate. If not dissociated, results will be
falsely decreased
- Ferrous form is measured

B. Quantitate transferrin
by adding Ferric ions more than the normal amount to make sure that the binding site of transferrin will be
saturated to measure Total binding iron capacity (TIBC)
Total binding iron capacity (TIBC)
- measures the functional ferrous binding sites of transferrin.

Transferrin saturation = serum iron/ TIBC x 100

TIBC may vary from 240 460 ug/dL

Transferrin saturation ranges between 20 -50 %

- If TIBC increases, transferrin also increases

- If transferrin is high, there will be more binding sites for iron

TIBC increased in
Pregnancy- because it produces for both the mother and the baby
IDA - there will be no iron left to attach to the receptor of the transferrin.
Acute hemorrhage when blood is lost, iron levels decrease
Destruction of hepatic cells

- Iron levels are higher in the morning

- Collect samples in the morning like in inorganic phosphates
- add more than enough amounts of iron

Non iron deficiency anemia have low TIBC because iron levels are still normal

TIBC = UIBC + Serum iron

Reference value
Male or female: 245 425 ug/dl
 >40 yrs: 10 250 ug/dl
Newborn or child: 150 200 ug/dl

UIBC (Unsaturated iron binding capacity)

Measures the reserve iron binding capacity of transferrin

UIBC = TIBC serum iron

Reference value:
20 50%

Ratio
1:3 normal individual
1:5 IDA (increased transferrin, decreased iron)

Serum transferrin
ST (mg/dl) = TIBC (ug/dl) x 0.70

C. Voltametry

D. Zinc protoporphyrin/heme ratio (ZPP/H)

A screening test and not diagnostic

for ida measure iron, the idc and the transperrin saturation.

- Prepare cyanmethemoglobin

- Drop blood

- Read on the spectrophotometer at 424 nm

Normal range:
30 80 mmol/L

Disadvantage:
- The result of ZPP/H is normal for thalassemia patients, it is abnormal for IDA.

Thalassemia
-There is something wrong in the globin chain

MISCELLANEOUS ELECTROLYES
(Page 150 151)