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CCHM 312
LECTURE / SECOND SEMESTER
Dianne Rose C. Mendoza, RMT, MPH

WEEK 4 & 5: WATER BALANCE AND ELECTROLYTES

BODY WATER

Bulk of body mass  WATER

Constitutes the medium by which solutes are dissolved and by which metabolic reactions
take place

Two main compartments:

 Intracellular Fluid
 Extracellular Fluid

DISTRIBUTION

• 40-75% - AVERAGE WATER CONTENT of the human body

• ECF – 1/3 (16 L)

- intravascular extracellular fluid (PLASMA)

PHYSIOLOGIC RESPONSE (INCREASED ECF OSMOLALITY)
- interstitial cell fluid
ANTIDIURETIC HORMONE (ADH) or Vasopressin release via hypothalamic
• ICF – 2/3 (24 L)
chemoreceptors
• NORMAL PLASMA - 93% water and 7% solutes (glucose, lipids, NPN, amino acids
Stimulation of the HYPOTHALAMIC THIRST CENTER
and ions)
Redistribution of water from the intracellular fluid compartment

OSMOLALITY
PHYSICAL PROPERTY of a solution that is based on the concentration of solutes
(expressed as millimoles) per kilogram of solvent (w/w)
Parameter to which the HYPOTHALAMUS responds affects the Na+ concentration in
PLASMA
RESPONSES TO CHANGES IN BLOOD OSMOLALITY
REGULATION OF ECF VOLUME
• Regulation of Renal Excretion of Sodium or GLOMERULAR FILTRATION RATE
 70% of Na is reabsorbed by the earlier parts of the renal tubule
• Aldosterone via RAA System  Juxtaglomerular cells of the kidneys release
RENIN  converts angiotensinogen  angiotensin I  Angiotensin II  stimulates
adrenal cortex to produce Aldosterone  promote retention of sodium and excretion of
potassium

DISORDERS OF WATER BALANCE

• DEHYDRATION

- Pure Water loss or deficit  Leads to INCREASED ECF Osmolality

 Compensates by recruiting water from the ICF
 LOWERS total BODY WATER but total BODY SODIUM
remains NORMAL

- Water and Sodium Loss  HYPOVOLEMIA readily takes place

 OVERHYDRATION  excessive intake of water or excessive
reabsorption of water

WHAT ARE ELECTROLYTES

• Electrolytes are ions that carry an electric charge. (ANIONS/CATIONS)

FORMULA FOR OSMOLALITY • Electroneutrality

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• Dissociation of solutes into charged particles (ions) depends on the chemical • For every 100 mg/dL INCREASE in blood glucose, serum sodium DECREASES by
composition of the compound and on the concentration of other charged particles in the 1.6 mmol/L
medium

REGULATION OF SODIUM
REGULATION OF ELECTROLYTES
• Diet
ACTIVE TRANSPORT - mechanism that REQUIRES ENERGY to move ions across
cellular membranes • Kidney  renal threshold for sodium (110-130 mmol/L)

DIFFUSION - PASSIVE movement of ions across a membrane. - 70-80%  reabsorbed at the proximal tubule

• RAA  release of ALDOSTERONE

FUNCTIONS: • ATRIAL NATRIURETIC FACTOR (ANF)  produced by the ATRIAL
MYOCARDIUM; promotes natriuresis and relaxation of the vascular smooth muscle
Volume and osmotic regulation

Myocardial rhythm and contractility

HYPONATREMIA
Cofactors in enzyme regulation
• is an electrolyte disturbance in which the sodium concentration in the serum is
Regulation of adenosine triphosphatase (ATPase) ion pumps
LOWER THAN NORMAL.
Acid-base balance
• Hyponatremia is defined as a serum level of less than 135 mEq/L and is considered
Blood coagulation SEVERE when the serum level is below 125 mEq/L.

Neuromuscular excitability

Production and use of ATP from glucose

ANION GAP

Refers to the difference between the sums of the concentration of the Principal
CATIONS (Na+ & K +) and of the Principal ANIONS (Cl- & HCO3- )

CAUSES OF HYPONATREMIA:

 Use of DIURETICS
INCREASED ANION GAP
 Syndrome of Inappropriate ADH (SIADH) secretion
 Uremia
 Ketoacidosis (Starvation or Diabetes)  Aldosterone deficit secondary to Addison's disease
 Methanol, Aspirin, or ethylene glycol poisoning
 Severe dehydration  BARTTER'S SYNDROME - it is a rare condition wherein sodium
chloride gradients CANNOT FORM in the loop of Henle causing the
 Lactic Acidosis
retention of chloride ion that is not available for the countercurrent
DECREASED ANION GAP mechanism.

 Multiple myeloma  DIABETIC HYPEROSMOLAR STATE - it causes EFFLUX of cellular

 Protein and instrument error water with consequent osmotic dilution of serum sodium.

 Congestive Heart Failure

SODIUM
 Azotemia
• It is the MAJOR CATION in the extracellular fluid (ECF)
 Burns
• It plays a central role in maintaining the normal distribution of water and osmotic
pressure in the ECF compartments.  Vomiting

• RENAL REGULATION
SYMPTOMS OF HYPONATREMIA
• Principal osmotic particle outside the cell

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• 125-130 mmol/L  GASTROINTESTINAL (GI)

• Below 125 mmol/L  NEUROPSYCHIATRIC

- nausea and vomiting

- muscular weakness
- headache, lethargy, and ataxia

• Severe symptoms

– seizures, coma, and respiratory depression.

• Below 120 mmol/L for 48 hours or less (ACUTE HYPONATREMIA)  is

considered a medical emergency.

PSEUDOHYPONATREMIA

- occurs when Na+ is measured using indirect ion-selective electrodes (ISEs) in a

patient who is HYPERPROTEINEMIC or HYPERLIPIDEMIC.

HYPERNATREMIA

•It is a serum sodium concentration ABOVE THE UPPER LIMIT of the reference
interval

SYMPTOMS OF HYPERNATREMIA

• CNS  altered mental status, lethargy, irritability, restlessness, seizures, muscle

twitching, hyperreflexes, fever, nausea or vomiting, difficult respiration, and increased
thirst REFERENCE INTERVAL

• 160 mmol/L is associated with a mortality rate of 60%–75%. • SERUM - 135-145 mmol/L
• URINE - 40-220 mmol/L
• CSF - 138-150 mmol/L

POTASSIUM

• It is the Major INTRACELLULAR CATION

• Its functions include e regulation of:

- Neuromuscular excitability
- Contraction of the heart
- Intracellular fluid volume
- Hydrogen ion concentration

REGULATION OF POTASSIUM

• Na+-K+ ATPase pump  fueled by oxidative energy  transports K+ into the cell
against a concentration gradient
CAUSES OF HYPERNATREMIA
• Diffusion of K+ out of the cell into the ECF and plasma (decreased pump activity):
 Diabetes insipidus
 Hyperaldosteronism – Depletion of metabolic substrate  e.g. glucose for ATP production
 Hyperadrenocorticism – Competition for ATP between the pump and other energy consuming
activities
METHODS OF DETERMINATION – Slowing of cellular metabolism

• Ion-specific Electrodes

• Atomic Absorption Spectrophotometry (AAS) HYPERKALEMIA

• Flame Emission Spectrophotometry (FES) / Emission Flame Photometry (FEP) • It is a serum potassium concentration ABOVE THE UPPER LIMIT of the reference
interval.
• COLORIMETRIC METHOD – Albanese Lein
• Hyperkalemia is seen in the following conditions:
– Combining SODIUM with ZINC URANYL ACETATE  sodium uranyl
acetate precipitate  addition of water produces YELLOW solution – Dehydration
– Diabetes insipidus
– Hypoadrenalism
– Acidosis
– Hemolysis

SYMPTOMS OF HYPERKALEMIA

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• muscle weakness, tingling, numbness, or mental confusion

• by altering neuromuscular conduction

• Hyperkalemia DISTURBS CARDIAC CONDUCTION  cardiac arrhythmias and

possible cardiac arrest.

• 6–7 mmol/L may alter the electrocardiogram

• >10 mmol/L may cause FATAL CARDIAC ARREST

HYPOKALEMIA

 acute myelogenous leukemia

 acute myelomonocytic leukemia
 acute lymphocytic leukemia

ANALYTICAL METHODS

• Ion Selective Electrode (ISE) is the METHOD OF CHOICE

HYPOKALEMIA • Atomic Absorption Spectrophotometry (AAS)

• It is a serum potassium concentration BELOW THE LOWER LIMIT of the • Flame Emission Spectrophotometry (FES)
reference interval
REFERENCE INTERVAL:
• It is seen in the following conditions:
• SERUM 3.5 – 5.1 mmol/l
- Infusion of insulin to diabetics
- Alkalosis • PLASMA Male: 3.5 – 4.5 mmol/l
- Vomiting
Female 3.4 – 4.4 mmol/l
- Over hydration
- Use of Loop diuretics • URINE (24 h) - 25 – 125 mmol/day

◦ Syndrome of Inappropriate ADH (SIADH) secretion

◦ BARTTER'S SYNDROME (it is a condition whose primary cause is the excess CHLORIDE
excretion of potassium)
• It is the Major EXTRACELLULAR ANION.
SYMPTOMS OF HYPOKALEMIA
• Together with sodium, they represent the majority of the osmotically active
• 3 mmol/L constituent of the plasma.

• Weakness • Maintaining electrical neutrality

• Fatigue • Regulate fluid content on the body and its influence in the kidney

• Constipation

• Can lead to muscle weakness or paralysis HYPERCHLOREMIA

• Sudden death would be caused by arrythmia • It can be seen in the following conditions:

– Dehydration
– Renal tubular acidosis
– Acute renal failure
– Metabolic acidosis associated with prolonged diarrhea

HYPOCHLOREMIA

• It is seen in:

– Prolonged vomiting
– Profuse sweating
– Increased gastric juice secretion

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– Salt-losing nephritis • PTH also stimulates renal production of ACTIVE VITAMIN D
– Addison’s disease

ANALYTICAL METHODS
REGULATION (VITAMIN D)
• Ion-selective electrode
• Vitamin D3 (CHOLECALCIFEROL) - obtained from the diet or exposure of skin to
• MERCURIMETRIC TITRATION (Schales-Schales method) sunlight.

- Colorimetric method uses mercuric thiocyanate and ferric nitrate to form • Vitamin D3  25-hydroxycholecalciferol (25-OH-D3)  1,25-
a REDDISH-COLORED complex with a peak at 480 nm. dihydroxycholecalciferol (1,25-[OH]2-D3)  BIOLOGICALLY ACTIVE FORM

• Coulometric-Amperometric Titration (Cotlove Chloridometer) • This active form of vitamin D INCREASES Ca2 ABSORPTION in the
INTESTINE and enhances the effect of PTH on bone resorption.
REFERENCE INTERVAL

• NORMAL serum concentration 98 – 106 mmol/L

REGULATION (CALCITONIN)
• DAILY URINARY OUTPUT: 110 – 250 mmol/L
• CALCITONIN  MEDULLARY CELLS of the Thyroid Gland

CALCIUM • Secreted when the concentration of Ca2 in BLOOD INCREASES.

• It is the FIFTH (5 ) MOST COMMON ELEMENT and the most PREVALENT

TH
• Calcitonin exerts its Ca2-lowering effect by inhibiting the actions of both PTH and
CATION in the human body vitamin D.

FUNCTIONS • Not secreted during normal regulation of the ionized Ca2 concentration in blood, it is
secreted in response to a HYPERCALCEMIC stimulus.
• It is important in skeletal mineralization
DISTRIBUTION:
• It plays a vital role in:
 FREE or ionized form (50%)
- Blood coagulation
 Bound to plasma protein (40%)
- Neural transmission
 COMPLEX form (10%)
- Enzyme activity
- Maintenance of normal tone
CLINICAL SIGNIFICANCE
- Excitability of skeletal and cardiac muscle
• INCREASED calcium levels are seen in:
• It is involved in glandular synthesis and regulation of EXOCRINE and
ENDOCRINE GLANDS – Periods of rapid growth in children
– Pregnancy
• It preserves the cell membrane's integrity and permeability particularly in terms of
– Lactation
sodium and potassium exchange
• DECREASED calcium level is seen in:
REGULATION
– Old age
• PTH, vitamin D, and calcitonin, are known to regulate serum Ca2 by altering their
secretion rate in response to changes in Ionized Ca2 FACTORS INFLUENCING CALCIUM LEVELS:

• INCREASED calcium absorption

- Vitamin D (major stimulus of calcium absorption)

- Growth hormone
- Increased dietary protein

• DECREASED calcium absorption

- Formation of insoluble salts with phosphorus

- Phytic acid
- Dietary oxalate
- Fatty acids
- Cortisol

• INCREASED urinary calcium excretion

- Hypercalcemia
- Phosphate deprivation
- Acidosis
REGULATION (PTH) - Glucocorticoid
• PTH secretion in blood is STIMULATED by a DECREASE in ionized Ca2 and,
• DIMINISHED urinary calcium excretion
conversely, PTH secretion is STOPPED by an INCREASE in ionized Ca2
- PTH
• In the bone, PTH activates a process known as BONE RESORPTION, in which
- Certain diuretics
ACTIVATED OSTEOCLASTS break down bone and subsequently RELEASE Ca2
- Vitamin D
into the ECF

• In the kidneys, PTH conserves Ca2 by increasing tubular reabsorption of Ca2 ions
HYPERCALCEMIA

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• It is a condition characterized by an INCREASED serum calcium level
• It is associated with anorexia, nausea, vomiting, constipation, hypotonia, depression &
coma
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• HENLE’S LOOP is THE MAJOR RENAL REGULATORY SITE  50%–60%
of filtered Mg2+ is reabsorbed in the ascending limb
• renal threshold for Mg2+ is approximately 0.60–0.85 mmol/L (1.46–2.07 mg/dL)

CAUSES • Parathyroid hormone (PTH) INCREASES the renal reabsorption of Mg2+ and
enhances the absorption of Mg2+ in the intestine.
• The most common causes are:
• ALDOSTERONE and THYROXINE  opposite effect of PTH in the kidney 
– Primary hyperthyroidism increasing the renal excretion of Mg2+
- Multiple endocrine neoplasia
– Familial hypocalciuria hypercalcemia
- Vitamin D intoxication
HYPERMAGNASEMIA
- Thyrotoxicosis
- Hypoadrenalism – It is a condition with HIGH LEVEL of serum magnesium.
- Multiple myeloma
– Increased magnesium level in the BLOOD IS RARE and usually IATROGENIC.

HYPOCALCEMIA – ELDERLY and patients with BOWEL DISORDER and RENAL

INSUFFICIENCY are the MOST AT RISK.
• It is a condition characterized by a LOW serum calcium level.
– Clinical manifestations include hypotension, bradycardia, respiratory depression,
• Severe hypocalcemia will eventually lead to tetany. depressed mental status and electrocardiographic (ECG) abnormalities.

CAUSES

• The most common causes are:

- Hypoparathyroidism
- Pseudohypoparathyroidism
- Deficiency in Vitamin D or its metabolite
- Chronic renal failure
- Hypomagnesemia
- Acute pancreatitis

ANALYTICAL METHODS

• TOTAL CALCIUM

o Spectrophotometric analysis with the metallochromic indicators.

- (Orthocresolphthalein complexone & Arsenazo III are MOST
WIDELY USED INDICATORS)
o Titration of fluorescent calcium complex with ethylene diamine tetra acetic
acid (EDTA) or ethylene glycol tetra acetic acid (EGTA).
o Atomic Absorption Spectrophotometry (AAS)
o Clark and Collip Method (Redox Titration Method)

• IONIZED CALCIUM

o Ion-Selective Electrode (ISE) for Calcium

REFERENCE INTERVAL:

PLASMA/SERUM

• 8.8-10.3 mg/dL (2.20-2.58 mmol/L) TOTAL CALCIUM in adults

• 4.6-5.3 mg/dL (1.16-1.32 mmol/L) IONIZED CALCIUM in adults

URINE:
HYPOMAGNASEMIA
• 300 mg/day (7.9 mmol/day) in NORMAL adults
• It is a condition with LOW serum magnesium level

• The most common causes of hypomagnesemia are:

MAGNESIUM
- Loss of magnesium in the GI tract as in chronic diarrhea and malabsorption
• It is essential for the function of cellular enzymes and energy metabolism. steatorrhea
- Diabetes mellitus secondary to glycosuria and osmotic diuresis
• It has an important role in membrane stabilization, nerve conduction, and ion
- Alcohol
transport and calcium channel activity.
- Stress
• It also plays an important role in maintenance of INTRACELLULAR K*
Concentration.

REGULATION

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• It is an IMPORTANT CONSTITUENT in nucleic acid, phospholipid and
phosphoproteins,

• It forms high energy compounds such as ATP and cofactor (NADP) and is involved
in intermediary metabolism and various enzyme systems.

• It is essential for muscle contractility, neurologic function, and electrolyte transport

and oxygen-carrying by hemoglobin.

HYPERPHOSPHATEMIA

• It is a condition characterized by a serum phosphorus concentration above the upper

limit of the reference interval.

• The usual causes are:

o DECREASE RENAL EXCRETION in acute and chronic renal failure

o INCREASE INTAKE with excessive oral, rectal, intravenous
administration.
o INCREASE extracellular load due to transcellular shift in acidosis
o Secondary to over medication with Vitamin D and production of Vitamin by
granulomatous tissue.

HYPOPHOSPHATEMIA

• It is a condition characterized by a serum phosphorus concentration below the lower

limit of the reference interval

• It can be seen in:

o Alcohol abuse
o Intestinal loss due to vomiting, diarrhea, and use of phosphate binding
antacids
o Induced by a shift of phosphorus from extracellular fluid into cells.
o Increased urinary excretion, secondary to hyperparathyroidism, renal
tubular defects and diuretic therapy.
o Decreased intestinal absorption is observed in malabsorption.
o Vitamin D deficiency and steatorrhea

ANALYTICAL METHODS

• Reaction of phosphate with ammonium molybdate (FISKE SUBBAROW)

ANALYTICAL METHODS
• Reduction of phosphomolybdate to molybdenum blue which can be measured at 600-
700 nm spectrophotometrically.
• TOTAL MAGNESIUM
• Enzymatic method
o Atomic Absorption Spectrophotometry (AAS) is the REFERENCE
METHOD but it is NOT ROUTINELY DONE in the clinical laboratory. REFERENCE INTERVAL

o Photometric methods on automated analyzers - These methods employ

 ADULT: 2.8-4.5 mg/dL (0.89-1.44mmol/L)
metallochromic indicators or dyes such as Calmagite, Formazan Dye,
 CHILDREN: 4.0-7.0mg/dL (1.29-2.26mmol/L)
Magon, and Titan Yellow Dye.

• Ionized (Free) Magnesium ELECTROLYTE AND RENAL FUNCTION

• Ion-Selective Electrode for magnesium RENAL TUBULES

- Intracellular Magnesium • Phosphate reabsorption is inhibited by PTH and INCREASED BY 1,25-

dihydroxycholecalciferol.
• Fluorescence measurement using furapta (magnesium binder)
• EXCRETION OF PO4 is stimulated by CALCITONIN.
• Nuclear magnetic resonance spectroscopy
• Ca2+ is reabsorbed under the influence of PTH and 1,25-dihydroxycholecalciferol.
• Ion selective microelectrode
• CALCITONIN stimulates excretion of Ca2 +.
• Electroprobe microanalysis
• Mg2 + REABSORPTION occurs largely in the thick ASCENDING LIMB OF
REFERENCE INTERVAL HENLE’S LOOP.

 1.6 - 2.6 mg/dL • Cl is reabsorbed, in part, by PASSIVE TRANSPORT in the proximal tubule along
 0.66 - 1.07 mmol/L the concentration gradient created by Na.

PHOSPHORUS

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