LECTURE 4:

Carmina Bianca M. Salumbides, RPh

Part I
 INTRODUCTION

 What are ELETROLYTES?

 Electrolytes concentration COMPUTATION

 Major Physiological Ions

What is Homeostasis?
EXTERNAL STIMULUS
 The ability of the body to
regulate, to seek and maintain a
condition of EQUILIBRIUM or
STABILITY within its INTERNAL Internal
environment
ENVIRONMENT when dealing
with external changes.
 Regulatory mechanisms:
– pH Control – Buffer Systems
– Ionic Balances
 REPLACEMENT THERAPY
– Osmotic Balances
– Thermoregulatory Controls  Electrolytes
– Feed-back mechanisms  Acids and Bases
 Blood products
 Carbohydrates
 Amino acids
 Proteins
• A SOLUTION is the homogenous product obtained when a substance (the
SOLUTE) is dissolved in the SOLVENT.

• SOLUTES are classified according to their behaviour when an electric

current is passed through the solution
• ELECTROLYTES – dissociate into ions and conduct electric current
– NaCl  Na + Cl
• NON-ELECTROLYTES – do not dissociate (remain intact) and do not
conduct electric current
– Urea and Dextrose
The electrolyte concentration will vary with a particular fluid compartment
[3] COMPARTMENTS
 Intracellular fluid
 Interstitial fluid
ECF
 Plasma or Vascular Fluid

Each compartment has distinct solute patterns.

Solution in each compartment is IONICALLY BALANCED.
Na and Cl ions  ECF
K, Mg and PO4 (HPO4)  ICF
 Electrolytes in body fluids play an important role in maintaining the acid-
base balance in the body, in controlling body water and help to regulate
body metabolism.
 mEq - Used to express the concentration of electrolytes in solution
(US)
 It is related to the total number of ionic charges in solution and takes note the
valence of the ions
 It is a UNIT OF MEASUREMENT of the amount of chemical activity of an
electrolyte
 Internationa System (SI) – Molar concentrations are used to
express most clinical laboratory values, including those of electrolytes
 mmol/L and umol/L
 Normal Conditions – equal number of Anions and Cations
 NOTE: the total concentration of cations always equals the total
concentration of anions
[Any number of mEq of any cations always react with
precisely the same number of mEq or any anions]
for a chemical compound:
mEq of the CATION = mEq of the ANION = mEq of the COMPOUND
Example:
 KCl dissolved in water gives 40 mEq of K = 40 mEq of Cl = 40 mEq of KCl
• Conversion of concentration of electrolytes (mEq/unit or volume 
weight/unit of volume) or vice versa (NOTE: Table 5-3)
What is the concentration, in mg/mL, of a solution containing
2 mEq of Potassium chloride per mL?

Note the following:

 The units given= mg/mL and mEq/mL
 What is asked? = covert mEq/mL to mg/mL
 Looking for mg/mL
 What formula will be used?
What is the concentration in grams per mL, of a solution
containing 4 mEq of Calcium Chloride (CaCl2.2H2O) per mL?
 NOTE: the water of hydration molecules does not interfere in the
calculation as long as the correct molecular weight is used.
 Units given; mEq/mL and g/mL
 What is asked? To convert mEq/mL to g/mL
looking for g/mL
 What formula will be used?
What is the percent (w/v) concentration of a solution 100
mEq of Ammonium Chloride per liter?
 Units given: Percent w/v = g/mL and mEq/L
 What is asked? Percent Weigh/Volume (%)

2 approaches:
(1) Convert 100 mEq/L into mg/L

(2) Get the % w/v of the solution

mg/L  g/mL
A solution contains 10mg/100mL of K ions. Express the
concentration in terms of mEq/L.

A solution of 10mg/mL of Ca ions. Express this concentration

in terms of mEq/L.
NOTE:
 Units given
 What is asked?
 Formula to be used
A magnesium level in blood is determined to be 2.5 mEq/L.
express this concentration in terms of mg/L.

How many mEq of KCl are represented in a 15-mL dose of a

10% KCl Elixir?
NOTE:
 Units given
 What is asked?
 Formula to be used
How many mEq of Magnesium Sulfate are represented in 1 g
of anhydrous magenesium sulfate?

How many mEq of KCl are represented in a 15-mL dose of a

10% KCl Elixir?
NOTE:
 Units given
 What is asked?
 Formula to be used
How many mEq of Na would be contained in a 30-mL
dose of the following solution?
Disodium Hydrogen Phospate = 18g
Sodium Biphosphate = 48g
Purified water = 100mL

MW of Na2HPO4.7H2O = 268 valence (2)

MW of NaH2PO4.H2O = 138 valence (1)
A person is to receive 2 mEq of sodium chloride per
kg of body weight. If the person weighs 132lb, how
many mL of a 0.9% Sterile NaCl should be
administered?

NOTE:
 Interconversion of lb to kg
 Formula of % w/v
• MAJOR EXTRACELLUAR ANION
• Principally responsible for maintaining proper hydration, osmotic
pressure, acid-base balance and normal cation-anion
balance in the vascular and interstitial fluid compartments
• CHLORIDE SALTS are preferred dosage form (providing the
pharmaceutical and toxicological criteria are met)
• Main source – FOOD
• Rapidly and completely absorbed from intestinal tract
• RDA – 5 – 10g as NaCl
• Eliminated by Glomerular filtrations (undergo tubular
reabsorption)
 CHLORIDE

Causes:
 Salt-losing nephritis associated with chronic pyelonephritis
 lead to lack to tubular reabsorption of chloride ions
 Metabolic Acidosis
 Diabetes Mellitus
 Renal Failure
(Replacement of chloride by acetoacetate and phoshpate)
 Prolonged vomiting (loss of gastric HCl)
 CHLORIDE

Causes:
 Dehydration
 Decreased Renal blood flow
 Congestive heart failure severe renal damage
 Excessive chloride intake
• HPO4 - PRINCIPAL ANION of the INTRACELLULAR
FLUID COMPARTMENT
• Food sources:
– Milk (Products), egg yolk, meat, whole grains, legumes and nuts
• Phosphorous RDA – ~ 0.7 - 0.8g
• Readily absorbed and excreted in the kidneys
– Vit D aids Phosphate intestinal absorption
– Proximal tubule (Reabsorption)
• Mostly stored in BONES
Biochemical functions
 Hexoses are metabolized as Phosphates
 Glycolysis (Aerobic and Anaerobic pathway)
 ATP generation
 Involves KINASES -> catalyze phosphorylation
 Phosphoanhydride bond
 HIGH-ENERGY BOND  ATP
~ 8000 cal/mole
released during the
hydrolysis of a
pyrophosphate bond
Biochemical functions
 Phosphate Buffer system
 Acid-base balance (Physiologically
and pharmaceutically
 Phosphorus is essential for proper Calcium Metabolism
 Phosphorus is essential for normal bones and teeth development
 Component of HYDROXYAPATITE
- the main calcium salt found in
the bones and teeth
DIHYDROGEN PHOSPHATE (H2PO4)
 Only the form that will be absorbed from the intestines
 The only form found in the acid stomach and in the upper part of the
duodenum
 At pH 6.8 – exists as a 1:1 ration of HPO4/H2PO4

MONOHYDROGEN PHOSPHATE (HPO4)

 Poorly absorbed  used as SALINE CATHARTICS
PHOSPHATE ACIDS
 ORTHOPHOSPHORIC ACID
 “Most highly hydroxylated” form
 H3PO4

 METAPHOSPHORIC ACID
 Loses the equivalent of one
molecule of water
 SODIUM METAPHOSPHATE (aka Graham’s Salt)
 Used as Water Softening agent
NOTE: Table 5-4
HYPERPHOSPHATEMIA
Causes:
 Hypervitaminosis D – enhances intestinal absorption
 Renal Failure – inability to excrete phosphate in urine
 Hypoparathyroidism
Complication:
 Formation of phospahtic urinary calculi (Kidney stone) -> kidney damage
 Treatment:
– Basic Aluminum Carbonate – Al (OH) CO3 (Basaljel)
• Remove dietary phosphate by excreting in the feces as slightly soluble
ALUMINUM PHOSPHATAE
HYPOPHOSPHATEMIA
Causes:
 Vitamin D deficiency (Rickets)
 Hyperparathyroidism
 Lack of phosphate reabsorption due to other causes (Infections, cancers.
Etc.)
 Long-term aluminum hydroxide gel antacid therapy
 aluminum hydroxide gel forms insoluble (slightly soluble) Aluminum
phosphates  Preventing absorption
Complications:
 Lack of phosphate source
 PARATHYROID HORMONE (PTH) is
released by the parathyroid gland in the neck.
It regulates the blood levels of both CALCIUM
AND PHOSPHATE.
 Stimulates production of the biologically-active
form of vitamin D within the kidney
ACTIVE FORM – 1,25-dihydroxyvitamin D3 (acts
as a steroid hormone)
 Facilitates mobilization of calcium and phosphate
from bone
 Promotes renal tubular excretion of
phosphates in the urine (proximal tubule)
 SECOND MOST PREVALENT ANION in the
EXTRACELLULAR FLUID COMPARTMENT
 Biological Function
 Bicarbonate/Carbonic Acid Buffer system – the MOST important
buffer system in the body
 85% of HCO3 is reabsorbed in the PROXIMAL TUBULE (KIDNEYS)
 METABOLIC ACIDOSIS
 due to LACK of BICARBONATE IONS
 METABOLIC ALKALOSIS
 due to EXCESS BICARBINATE IONS
 PRINCIPAL EXTRACELLULAR CATION
 Responsible for maintaining normal hydration and osmotic pressure
 RDA < 2300mg/day
 KIDNEY – regulator of sodium content
 Hormonal control and Sympathetic Control
(Renin – Angiotensin – Aldosterone - System)  RAAS
 Na Reabsorption*
 Proximal (65 – 67% Na) and Loop of Henle (20 – 30% Na) –
regardless of the Na load (total amount of Na in the body), a certain % od Na is
reabsorbed
 Na Reabsorption
 DISTAL TUBULE (5-10% Na) and COLLECTING TUBULE/DUCT (2-5% Na)
 Regulated by R-A-A-S (activation)  Na REABSORPTION

JGA

Afferent
Arterioles

Distal Tubules
RENIN is a proteolytic (enzymatic) hormone
released/secreted by GRANULAR CELLS
(afferent arterioles) in the JGA in
response to:
 Reduced NaCl load
 Reduced Extracellular fluid (ECF) / Blood
volume (Body Fluid)
 Reduced Mean Arterial Pressure (MAP)

RENIN CONVERTS ANGIOTENSINOGEN TO

ANGIOTENSIN I
RENIN clips off 10 amino acid peptide
from angiotensinogen 
ANGIOTENSIN I

ACE – ANGIOTENSIN CONVERTING

ENZYME
 Removes 2 amino acid from Angiotensin I
forming ANGIOTENSIN II
ANGIOTENSIN II
 Potent VASOCONSTRICTOR  increases the peripheral vascular
resistance  increase in Mean Arterial Pressure  increase BP
 Increase THIRST (fluid intake)
 MAIN STIMULUS for the secretion of ALDOSTERRON and VASOPRESSIN
ALDOSTERONE VASOPORESSIN
Mineralocorticoid hormone produced by Aka ANTIDIURETIC HORMONE (ADH)
zona glomerulosa of the adrenal cortex synthesized in the hypothalamus and
Site of action: Principal cells of the distal stored and released from the
and collecting tubules PITUITARY GLANDS
MOA: Promotes Na (Salt) Retention or Site of action: Principal cells of the
Reabsorption and K secretion (Collecting distal and collecting tubules
Tubule) MOA: WATER CONSERVATION
 Sodium and water reabsorption or conservation is important in
maintaining osmotic balance in the body. This helps in preserving the
sufficient blood volume necessary to keep body organs well supplied
with blood (Adequate blood perfusion).
DRUGS AFFECTING SODIUM REABSORPTION
 DIURETICS
 Loop Diuretics (Thick Ascending Loop of Henle) – Furosemide, Ethacrynic Acid, Torseminde,
Bumetanide
 Thiazide Diuretics (Early Distal Tubule) – Hydrochlorothiazide, Chlorothiazide, Indapamide
 Potassium Sparing Diuretics – Spironolactone and Eplerenone (ALDOSTERONE ANTANGONIST),
Triamterene and Amiloride
 ACE INHIBITORS “-PRIL”
 Enalapril, Captopril, Benazarpil, Fosinopril, Lisinopril, Moexipril, Quinapril, Perindopril, Ramipril
Causes:
 Extreme urine loss (diabetes insipidus - defined as the passage of large
volumes (>3 L/24 hr) of dilute urine)
 Metabolic Acidosis
 Leads to excretion of Na ions in the urine
(Compensatory mechanism)
 Addison’s Disease
 Insufficient production (amount) of Cortisol,
Aldosterone and other hormones
 Diarrhea and Vomitting
 Kidney damage
Causes:
 Hyperadrenalism (Cushing’s Syndrome)
 Excessive production of CORTISOL due to excessive production of ACTH by the
pituitary gland (presence of tumor)
 Severe dehydration Neocurtasal, Co-Salt
 Certain types of brain damage/ injury Sodium-free salt substitutes
NEOCURTASAL
 Excess treatment with sodium salts (Potassium chloride, Glutamic acid,
K glutamate, Ca Silicate, Tribasic
COMPLICATIONS: Cs PO4, KI
 Hypertension (BP = PVR x CO) Co-SALT
(Choline, KCl, Ammonium Chloride,
 Congestive Heart Failure (Edema) Tricalcium Phosphate)
 MAJOR INTRACELLULAR CATION
 Intracellular concentration is 23x greater that its concentration outside
the cell
 ACTION POTENTIAL – NERVE IMPULSE
 Involves changes in ION gradients inside and outside the cells
 Facilitated by Voltage gated ion channels

DENDRITES
CELL BODY
AXON
IMPORTANT BIOLOGICAL FUNCTIONS:
 Maintenance of proper ELECTRICAL CONDUCTION in CARDIAC and SKELETAL MUSCLES (muscle
and nerve excitability)
 Influence on the body’s water balance (Intracellular volume)
 Plays a role in acid-base equilibrium
REGULATION:
 KIDNEYS – Reabsorption (Proximal and TAL) and
Secretion (Collecting tubule)
 Aldosterone
 Arterial pH
 Potassium intake
 Insulin – stimulate cellular uptake of K
 Sodium delivery to distal tubules
 The NERVOUS
Between SYSTEM
impulse, carries signals
the membrane is saidthrough
to be inthe
its
body in the form of RESTING
nerve impulse/
STATE ACTION POTENTIAL
ACTION POPTENTIAL
*RESTING STATE INNERis a wave of CHEMICAL
SURFACE and
of the cell
ELECTRICAL
membrane: has change
a more that movesCHARGE
NEGATIVE along the
(-)
membrane
OUTER SURFACE of the
: has nerve
a more cell. CHARGE
POSITIVE
(+)
 The stimulus changes the permeability of the cell membrane to
Na and K. This alters the charge in the cell body and trigger a
A Meanwhile
stimulus thethe
cause NaVGions insideto the
channel opencell
anddiffuse
Na ion
signal called action potential and moves down the axon.
to the
rush adjacent
into theVG
cell.
Theareas
cell causing
become slightonchange
positive the insidein and
the negative
polarityoncauses
channels in the membrane open and close depending on the the the VGVery
outside. Na
channel
quickly the Naalong the membrane
channels close while the to VG
open and again
K channel openNa ions rush
allowing the
voltage charges across the membrane. When no Nerve signals
Kinionand
are being transmitted, these channels are closed of the
the action potential
to rapidly diffuse out that spread the
returns to be + adjacent part
on the outside and
negative
neuron. In thisonway,
the inside. And thepotential
the action K channeltravels
closes. down the
axon like a wave.
ACTION POTENTIAL Na

K
K

Na

Na
K Na
Na
 Depolarization- change in cell membrane potential
making it more positive, less negative
 Influx of Na/Ca ions (+ charged)

Excitatory NT:
Aspartate/Glutamate
Acetycholine
ACTION POTENTIAL Na

Na

Na
 Hyperpolarization- Change in the cell membrane
potential making it more negative
 Influx of Cl ion (negatively charged)
 Efflux of K ion (positively charged)

Inhibitory NT:
GABA
Glycine
 Has diuretic effect
 Renal COLLECTING TUBULE serves as the most important site of K
secretion
 PRINCIPAL CELLS ALDOSTERONE regulates K secretion
 Na Reabsorption and Na Reabsorption
 K secretion
 INTERCALATED CELLS
 H secretion (alpha cells) – in response to Acidic body fluid (ACID-BASE Balance)
 HCO3 reabsorption (beta cells)
 K reabsorption (beta cells)
 ACID-BASE status of the body affect the magnitude of K secretion
HYPOKALEMIA
 May occur due to vomiting, diarrhea, burns, haemorrhages, diabetic coma,
overuse of thiazides and loop diuretics and ALKALOSIS.
 ALKALOSIS – Basic body fluid
 To increase the acidity of body fluid, H+ ions must be conserved by
reducing its secretion into the lumen, increasing K excretion in the urine
 HYPOKALEMIA

HYPERKALEMIA
 Less common and usually occurs in the presence of renal failure and
ACIDOTIC conditions
 99% is found/ stored in BONES
 ABSORPTION – the ionized water soluble salt form of calcium is
absorbed from the upper part of the small intestines (acidic
environment)
 Alkali environment causes precipitation of Calcium as DIBASIC
PHOSPHATE (CaHPO4), carbonate, oxalate and sulfate salts, and as
insoluble calcium salts  POORBLY ABSORBED
IMPORTANT PHYSIOLOGICAL FUNCTION:
 Vital to the EXOCYTOTIC RELEASE of Neurotransmitters, Insulin
(pancreas) and H ions (stomach)
 Blood Clotting and Muscle Contraction
Osteoclast
 The amount of phosphate in the blood affects the level of calcium in the
blood.
 Calcium and phosphate in the body react in opposite ways:
“as blood calcium levels rise, phosphate levels fall”
 If the calcium level is low, the parathyroid gland will release PTH, which tells the
kidneys to produce more active vitamin D. This helps the body to absorb more
dietary calcium and phosphorus through the intestine, tells the bone to release
calcium and phosphorus into the blood and tells the kidneys to excrete more
phosphorus in the urine.
 BLOOD CLOT

 Thrombin – Serine protease enzyme

 Prothrombin – Clotting factor II
NEUROTRANSMITTER RELEASE
MUSCLE CONTRACTION
Causes: Causes:
 Hyperparathyroidism  Hypoparathyroidism
 Hypervitaminosis D  Hypovitaminosis D
 Bone cancer  Osteoblastic metastasis
 Steatorrhea (fatty stool)
TREATMENTS:  Cushing’s syndrome
MOA: Reduce INTESTINAL ABSORPTION  Acute pancreatitis
 EDTA – ETHYLENE DIAMINE TETRAACETIC  Acute hyperphosphatemia
ACID
 Precipitate Calcium as insoluble salts
SEVERE FALL IN SERUM LEVELS
 Cellulose phosphate  Hypocalcemic tetany
 Form complex with calcium ions
• OSTEOPOROSIS
– Reduced volume of bone tissues per unit volume of
anatomical bones  FRAGILE and WEAK BONES
– TREATMENT:
• Calcium supplements
• PAGET’S DISEASE
– Characterized by initial phase of decalcification and
softening of the bones
– Followed by CALCIUM DEPOSITION with resultant
thickening and deformity
– TREATMENT:
• Phosphate salts
• Calcitonin
 SECOND MOST plentiful CATION in the intracellular fluid
 FOURTH MOST abundant CATION in the BODY
 SOURCE: Chlorophyll, nuts, legumes, whole grains
 50% of total body magnesium is combined with
calcium and phosphorus in bones
FUNCTIONS:
 Component of many enzymatic reactions such as carbohydrate, fat, and
electrolyte metabolism.
 Magnesium ions are indispensible in protein synthesis, for smooth functioning
of the neuromuscular system as well as membrane transport integrity
HYPOMAGNESEMIA Symptoms:
Causes:  Personality changes (after
depletion for 3-4 months
 Malnutrition
duration)
 Dietary restrictions
 Failure to gain weight
 Chronic Alcoholism
 Cardiac disturbances
 Faulty absorption or utilization
 Weakness
 GIT diseases
 Muscle fasciculation with tremor
 Medications
 Tetany
 PTH imbalances
 Increased reflexes
HYPERMAGNESEMIA Symptoms:
 Bradycardia
Causes:
 Flushing
 Increased magnesium intake  Sweating
in the setting of renal  Nausea and vomiting
insufficiency  Decreased Calcium levels
 Hepatitis  Decreased deep-tendon reflexes
 Addison’s disease  Flaccid paralysis
 Increased pulse rate and QRS
intervals
 Respiratory distress
Pharmacologic Action:
 IV and IM administration -> powerful general anesthetic action
(resembles that of choroform’s)
 Depressant action in the neurons and neuromuscular junction (Skeletal
Muscles)
 Excessive Magnesium ions  Decreases the amount of
Neurotransmitters released into the synapse
 CALCIUM ions relives the effect
 Magnesium salts (MgSO4) – used as CNS depressant in obstetrics,
convulsant states, and for symptoms of tetanus
ABSORPTION
 Retarded by ALKALINE SOLUTION
 SITE of ABSORPTION -> Duodenum
 Slow absorption leads to a SALINE LAXATIVE ACTION (upon the
ingestion of any water soluble magnesium compounds)

NOTE:
IV/IM administration should be avoided in patients with IMPAIRED RENAL
FUNCTION
TABULATION OF ELECTROLYTE PREPARATIONS
 Replacement Therapy
 Acid-Base Balance
 Combined Therapy
 PART II
ESSENTIAL and
NON-ESSENTIAL IONS