Laboratory aspect of electrolyte and

acid based disturbance

IRA PUSPITAWATI
CLINICAL PATHOLOGY AND LABORATORY MEDICINE DEPARTMENT
Electrolyte Imbalance
Introduction

 Electrolyte abnormalities are common in emergency

medicine and can vary greatly in importance, severity, and
symptoms.
 Asymptomatic electrolyte abnormalities can usually be
gradually corrected, but those that cause alterations in
consciousness or life threatening dysrhythmias require
immediate therapy to avoid permanent sequele or death.
ELECTROLYTE IMBALANCE

Dissorder of Dissorder of
Potassium Sodium

Hypokalemia Hyponatremia

Hyperkalemia Hypernatremia
HYPOKALEMIA
Hypokalemia

 Hypokalemia is the most common electrolyte

abnormality encountered in clinical practice. When it is
defined as a value of less than 3.5 mEq/L, hypokalemia
is found in more than 20% of hospitalized patients and
in 10 to 40% of patients treated with thiazide diuretics in
the outpatient setting.
Hypokalemia

•The K+ shift into the cell can cause severe

Intracellular hypokalemia.

shift •Alkalosis, insulin, b2 agonist can cause hypokalemia

by stimulating Na+K+ATP ase activity.

•Poor intake by itself is rarely a cause of hypokalemia

Reduced because it is usually accompanied by poor caloric
intake intake, which causes catabolism and release of K+
from the tissues.

Excessive • The most common cause of hypokalemia.

renal loss
 Hypokalemia

 Transmembrane electrical gradients

cause diffusion of cellular K+ out of cells
and Na+ into cells. Because the Na+-K+
pump, which reverses this process, is
stimulated by insulin and catecholamines
(through β-2-adrenergic receptors)
alterations in levels of these hormones
can affect K+ transport and its serum
level.
 Cells can act as buffers. In acidosis, cells
can take up H+ ions in exchange for K+
ions, and, in alkalosis, cells extrude H+
ions in exchange for K+ ions
Differential diagnosis of hypokalemia

 The first step in the differential diagnosis is to measure urinary excretion of K. If

urinary excretion is low (<20mEq/day or <0,001 mEq/mg) the cause is low intake,
extrarenal loss of K+ or intracellular shift.
 Superacute development of hypokalemia usually suggest intracellular shift as the
mechanism.
 The most common extrarenal loss is diarrhea, which can be suspected by history
and a low or negative urine anion gap (Urine Na+K+Cl-), the normal urine anion gap
is 40 mmol/24 hours.
 If urinaly excretion is normal or increased (urine K+>30 mEq/day or 0.02 mEq/mg of
creatinine) the cause is renal loss.
 Once a renal cause is suspected, the next step should be the measurement of
Plasma Renin Angiotensin (PRA) and plasma aldosterone.
Renin, Angiotensin, Aldosteron
Hypokalemia

 High PRA and high aldosterone suggest secondary

hyperaldosteronism which includes diuretic therapy, renal artery
stenosis, renin producing tumors, hereditary deffect in renal salt
transport (Barter syndrome).
 Low PRA and high aldosterone suggest primary
hyperaldosteronism which is caused by adrenal adenoma or
bilateral hyperplasia.
Control of potassium secretion
 Hypokalemia

 Increased excretion of potassium, especially coupled with poor intake, is the most
common cause of hypokalemia, and patients receiving diuretics represent the
single most common patient group encountered in clinical practice.

 Hypokalemia from thiazide diuretics occurs through increases in distal sodium

delivery in the nephron and by activation of the renin-angiotensin-aldosterone
system.
Mechanism of Thiazide
Hypokalemia

 Renal Tubular Acidosis (RTA) is characterized by the inability

of the tubules to secrete adequate hydrogen ion despite a
normal Glomerular filtration rate (GFR). Consequently
despite being in acidosis these patients are unable to
produce an acid urine (I.E Ph<5.3).
Hypokalemia

 Individuals with secondary hyperaldosteronism, whether it is due to

congestive heart failure (CHF), hepatic insufficiency, or nephrotic
syndrome, may also exhibit hypokalemia.
 Patients with renal tubular acidosis can become hypokalemic because a
defect in the distal tubule leads to increased potassium excretion.
 Administration of insulin may cause a reduction in serum potassium
because of insulin’s ability to stimulate the Na+K+ATPase pump and move
potassium Intracellularly; hypokalemia can be a dangerous complication
with intentional overdoses of insulin and during treatment of Diabetic
ketoacidosis (DKA).
Hypokalemia

 Clinical manifestation
Hypokalemia is usually asymptomatic
but can be manifested with nonspecific
complaints, including palpitations,
skeletal muscle weakness, easy
fatigability, depression, and muscle
pain.
Hypokalemic patients can demonstrate
first- and second-degree heart block,
atrial fibrillation, ventricular fibrillation,
and asystole. Hypokalemia can also
promote metabolic acidosis.
HYPERKALEMIA
Hyperkalemia

 Hyperkalemia defined as serum potassium level greater

than 5.0 Meq/L, is the most dangerous acute electrolyte
abnormality, potentially leading to life-threatening
arrhythmias and death.

 Upwards of 98% of potassium in the body is contained

intracellularly, whereas less than 2% remains circulating in
the blood. Serum potassium concentration is normally
between 3.5 and 5.0 mEq/L and is tightly regulated by the
kidney
Hyperkalemia

Shift of potassium from the cells to the ECF

Increased potassiun intake

Reduced potassium excretion

Hyperkalemia

 Extracellular potassium shift

Rhabdomyolysis or hemolysis, and acute acidosis.
Rhabdomyolysis and hemolysis can cause hyperkalemia when there
are accompanied by renal failure.
Digitalis intoxication ➔ Digitalis inhibit NA+K+ATPase pumps
 Increased intake of potassium
The ability of kidney to excrete potassium is so great that
hyperkalemia rarely occurs solely on the basis of increased intake of
potassium.
Pseudohyperkalemia

 Increase in potassium concentration only in the local blood vessel or in

vitro and has no physiologic consequences.
 Prolonged use of tourniquet with first exercises can increase the serum
potassium level by as much as 1 mmol/L. Thrombocytosis and
leucocytosis cause pseudohyperkalemia through potassium release from
the platelets and white blood cells, respectively during blood clotting.
Differential diagnosis of hyperkalemia

 First step is to rule out pesudohyperkalemia.

Pseudohyperkalemia should be suspected when conditions known to
cause pseudohyperkalemia such as thrombocytosis or in vitro hemolysis exist.
One pseudohyperkalemia is rule out, the next step is to differentiate among the
three major causes of hyperkalemia.
 Measurement of a 24 hour urine K+ will distinguish increased intake from the
other two causes. Although hyperkalemia due to a shift of K+ from the cell
would result increased urinary excretion of K+, renal excretiom of K+ is often
not increased, unless the patient is deliberately trying to decieve the
physician.
 Chronic hyperkalemia is almost always due to impaired renal excretion and
a 24 hour urine K+ measurement is rarely needed to proove impaired renal
excretion of K+ as the cause of hyperkalemia.
Hyperkalemia

 The most common cause of acute hyperkalemia is acute renal failure,

and this will be obvious from the serum creatinine and BUN
 For differential diagnosis of chronic hyperkalemia of renal causes, the frst
step is to measure plasma renin activity, plasma aldosterone and urinary
excretion of Na+, and K+. A very low urinaly Na+ and a low K+ in the
absence of polyuria suggest that the aldosterone effect is normal; in this
setting, K+ excretion is impaired by the reduced availability of Na+ and a
marked reduction in collecting duct urine flw.
 Markedly increased proximal reabsorbtion of Na+ due to low effective
vascular volume such as severe congestive heart failure, can cause
hyperkalemia by such mechanism.
 If urinary Na+ is adequate (>20 mmol/L), plasma renin activity and
aldosterone should be measured.
Hyperkalemia

 Clinical Manifestation:
 Patients with moderate to severe hyperkalemia may have
gastrointestinal effects such as nausea, vomiting, and
diarrhea often in association with their underlying disease.
Neuromuscular findings, including muscle cramps,
generalized weakness, paresthesias, tetany, and focal or
global paralysis, may be seen in patients with severe
hyperkalemia.
HYPONATREMIA
Hyponatremia

 Hyponatremia, defined as serum sodium concentration of

less than 135 mEq/L, is the second most common
electrolyte abnormality encountered in clinical practice.
 Generally clinical concern arises when the concentration
is less than 130 mmol/L.
Hyponatremia

 The most common causes of

severe hyponatremia in adults
are therapy with thiazides, the
postoperative state including
transurethral prostatectomy,
the syndrome of inappropriate
secretion of antidiuretic
hormone (SIADH), polydipsia in
psychiatric patients, and
unintentional water
intoxication.
Hyponatremia

 Clinical manifestation
Central nervous system (CNS) damage due to
hyponatremia may be caused by cerebral edema and
increased intracranial pressure, by Osmotic fluid shifts
during overly aggressive treatment, or by both.
Types of Hyponatremia

Hypovolemic hyponatremia

Hypervolemic hyponatremia

Euvolemic hyponatremia
Hypovolemic hyponatremia

 Hypovolemic hyponatremia, or hyponatremia in association

with dehydration, occurs when there is decreased
extracellular volume combined with an even greater loss of
sodium.
 Hyponatremia secondary to body fluid losses must be
differentiated from that due to renal losses. Hyponatremia
with dehydration due to body fluid losses includes sweating,
vomiting, diarrhea, and gastrointestinal suction.
Hypervolemic hyponatremia

 Hyponatremia with increased extracellular volume,

occurs when sodium and water are retained but water
retention exceeds sodium retention. Most of these
patients present with edema. Hyponatremia with
increased total body sodium occurs in patients with
heart failure, chronic renal failure, and hepatic failure.
 Euvolemic hyponatremia

 The final category of hyponatremia is

one in which patients are euvolemic
but have increased total body water.
Causes of this type of hyponatremia
include SIADH, psychogenic
polydipsia, hypothyroidism, diuretic
use in patients with mild CHF, and
accidental or intentional water
intoxication.
 These patients do not present with
edema because most of the
increased body water is intracellular
and not intravascular.
Sindroma of inapropriate ADH (SIADH)

 SIADH is an important cause of hyponatremia that occurs when normal

antidiuretic hormone secretion is lost and antidiuretic hormone is secreted
independently of the body’s need to conserve water. The process results from
excess antidiuretic hormone production that causes total body water to
increase, diluting the body’s sodium and causing the serum sodium to
decrease.
 Patients with SIADH have inappropriately concentrated urine despite a low
serum osmolality and normal circulating blood volume. Patients with SIADH
have excess total body water but no signs of edema, ascites, or heart failure
because most of the increased body water is intracellular, not intravascular.
Hyponatremia

 Clinical manifestation
 Nonspecific signs of hyponatremia include anorexia, nausea,
vomiting, and generalized weakness. Acutely hyponatremic
patients whose sodium level drops below 120 mE q/L during 24 to
48 hours may present with severe neurologic findings, including
confusion, seizures, cerebral edema, coma, and brainstem
herniation.
 Central nervous system (CNS) damage due to hyponatremia may
be caused by cerebral edema and increased intracranial
pressure, by Osmotic fluid shifts during overly aggressive
treatment, or by both.
Pseudohyponatremia

 Pseudohyponatremia
A spurious reduction in serum sodium concentration
caused by a systematic error in measurement. The most
common cause is in vitro hemolysis, a well known cause
of pseudohyperkalemia. Because cell lysis doesn’t
change osmolality of the plasma, any rise in serum
potassium must be met by a reciprocal decrease in
serum sodium.
Pseudohyponatremia

 Other cause of pseudohyponatremia include hyperlipidemia, hyperproteinemia

and increased viscocity of the plasma. The error in measurement in
pseudohyponatremia due to hyperproteinemia and hyperlipidemia results from
dilution of the sample as occurs with the common technique of indirect ion-
specific electrode measurement.
 In hypergammaglobulinemic states, such as Multiple myeloma, serum sodium
may be falsely low necause displacement of serum water by gamma globulins
but the sodium concentration is also truly low because cationic charges of
gamma globulins displace sodium to maintain electrical neutrality.
 Hyponatremia induced by hyperglycemia is nor pseudohyponatremia because
sodium concentration in the ECF is truly low, this occurs as a result of water shift
from the cell caused by hyperglycemia. Serum sodium is decreased by 1.6
mmol/L for every 100 mg/dL rise in serum glucose.
HYPERNATREMIA
Pathogenesis of Hypernatremia

 Hypernatremia is defined as an increased sodium concentration in

plasma water and is generally diagnosed at serum sodium level
>145 mmol/L.
 Whereas hyponatremia may not accompanied by hypoosmolality,
hypernatremia is always associated with an increased effective
plasma osmolality and hence with a reduced cell volume.
However, the Extracellular fluid (ECF) volume in hypernatremia
may be normal, decreased or increased.
Pathogenesis of Hypernatremia

• Kidney: diabetes insipidus, osmotic

diuresis
Loss of water • Gastrointestinal: osmotic diarrhea, gastric
suction

Reduced • Commonly in comatose patients

intake

• In conscious person won’t result

Gain of hypernatremia becuase a proportional
sodium water is retained to maintain normal body
fluid.
Other electrolytes imbalance

 Hypercalcemia
 Hypocalcemia
 Hypermagnesemia
 Hypomagnesemia
 Hyperphosphatemia
 Hypophosphatemia
ACID BASE DISTURBANCE
 DEFINITIONS OF ACID AND BASE

 Arrhenius’s definition: An acid is a substance that increases

the concentration of hydrogen ion (H+) when dissolved in
water, and a base is a substance that increases the
concentration of hydroxyl ion (OH−) when dissolved in
water.
DEFINITIONS OF ACID AND BASE

 Bronsted and Lowry’s definition:

An acid is a substance that donates a proton in a reaction, and a
base is substance that accepts a proton in a reaction.
 Because HCO3 − and CO2 are the major buffers of the body, pH is
typically expressed as a function of their ratio, ( the Henderson-
Hasselbalch equation) as follows:

 pH = 6.1+ log HCO3⁻ × 0.03

pCO2
 The Henderson-Hasselbalch equation indicates that pH
depends on the ratio of HCO3⁻ / pCO2.
 pH increases when the ratio increases (alkalosis),
 pH decreases when the ratio decreases (acidosis).
 The ratio may be increased by an increase in HCO3 ⁻
(metabolic alkalosis) or by a decrease in pCO2(respiratory
alkalosis).
 The ratio may be decreased by a decrease in HCO3 ⁻
(metabolic acidosis) or by an increase in pCO2 (respiratory
acidosis).
Acid-Base Disorders

Metabolic acidosis

Respiratoric acidosis

Metabolic alkalosis

Respiratoric alkalosis
METABOLIC ACIDOSIS

• Renal Acidosis
1

• Extrarenal Acidosis
2

• Lactic Acidosis
3
Causes of Metabolic Acidosis According to Net
Acid Excretion
Causes of L-Lactic Acidosis
 SERUM ANION GAP
Na+ − (Cl− + HCO3−) or
(Na+ + K+) − (Cl− + HCO3−)

total serum cations =

Na+ + unmeasured cations (UC),
total serum anions =
Cl− + HCO3− + unmeasured anions(UA).
Because total serum cations = total serum anions,
Na+ + UC = (Cl− +HCO3−) + UA.
Na+ − (Cl− + HCO3−) = UA − UC.
The anion gap = UA − UC
anion gap = Na+ − (Cl− + HCO3−),

The normal value : ± 12 mmol/L (8–16 mmol/L)

The anatomy of anion gap
Classification of Metabolic Acidosis by Anion Gap
Compensation of Metabolic Acidosis

 Compensation of metabolic acidosis is achieved by

hyperventilation, which results in decreased pCO2. The
compensation is moderately effective, and the maximal
compensation is completed within 12 to 24 hours.
 The formula that predicts the expected decrease in pCO2
(ΔpCO2) is as follows:
 METABOLIC ALKALOSIS
Mechanisms and Causes to Increase extracellular
Bicarbonate Concentration
Compensation of Metabolic Alkalosis

 Compensation of metabolic alkalosis is achieved by

hypoventilation that results in increased pCO2.
 In part because hypoxemia occurs inevitably with
hypoventilation in the absence of oxygen supplement,
among the four types of acid-base disorders,
compensation is least effective in metabolic alkalosis.
 The maximal compensation is completed within 12–24 hours.
Observations have shown that no matter how severe the
metabolic alkalosis, pCO2 rarely exceeds 60 mmHg unless a
complicating independent respiratory disorder that
compromises ventilation coexists.
 The formula that predicts the expected increase in pCO2
(ΔpCO2) is as follows:
RESPIRATORY ACIDOSIS
Compensation of Respiratory Acidosis

 The normal compensatory response to respiratory

acidosis is to increase HCO3 − concentration in an
attempt to minimize the reduction in pH.

 This occurs in two distinct stages:

1. tissue buffering of CO2, and
2. increased renal excretion of acid.
 Tissue Buffering
 This phase of compensation is extremely fast and occurs within
a second

KBuff is a non-HCO3− buffer

HBuff is cellular acid buffers,

The relationship between an increase in pCO2 (ΔpCO2) and

the increase in serum levels of HCO3 − (ΔHCO3−) in acute
respiratory acidosis is shown in the following equation:
 Renal Compensation
 Renal compensation for respiratory acidosis is delayed,
but it increases the HCO3− concentration to a much
higher level.
 The increased concentration of HCO3− is achieved by
increased net acid excretion, primarily in the form of NH4
+.
 Maximal compensation requires 5 days but is 90%
complete in 3 days
 The relationship between the increase in pCO2
(ΔpCO2) and the increase in HCO3− (ΔHCO3−) in
chronic fully compensated respiratory acidosis is
shown in the following equation :
RESPIRATORY ALKALOSIS
 Two types of compensation lower plasma HCO3− and
minimize the increase in blood pH in respiratory alkalosis:
tissue buffering and renal compensation.

 Tissue Buffering
 Compensation by buffering of HCO3 − is completed within a
second with the following reactions (Carroll, 1989):
 Renal Compensation
 Renal compensation of respiratory alkalosis is achieved by
reduction in net acid excretion (Carroll, 1989; Oh, 2003).
 This is achieved initially by increased excretion of HCO3−,
but later by reduced excretion of NH4+ and titratable acid.
 The magnitude of reduction in plasma HCO3−
concentration due to renal compensation can be predicted
from the following equation:
 Among the four types of acid-base disorders,
compensation is most effective in respiratory alkalosis;
pH after compensation sometimes returns to normal
levels. The process is completed within 2–3 days. When
complete compensation does occur, one should look
for evidence of complicating metabolic acidosis.
 MIXED ACID-BASE DISORDERS

 The term mixed acid-base disorder refers to a clinical condition

in which two or more primary acid-base disorders coexist.
 They generally present with one obvious disturbance with what
appears to be an inappropriate (excessive or inadequate)
compensation
Classification and Characteristics of Simple Acid-Base Disorders
Disorder Primary Change Compen- Expected Compesation
satory
Metabolic ↓↓↓ cHCO3_ ↓↓ pCO2 = 1,5( cHCO3_) + 8 ±2
Acidosis pCO2 pCO2 ↓ 1,0-1,3 mmHg for each 1 mmol/L ↓
cHCO3_
Metabolic ↑↑↑cHCO3_ ↑↑ pCO2 ↑6 mmHg for each 10 mmol/L ↑ in
Alkalosis pCO2 cHCO3_
Respiratory Acidosis
Acute ↑↑↑ pCO2 ↑ cHCO3_ cHCO3_ ↑ by 1,0 mmol/L for each 10 mmHg
↑ in pCO2
Chronic ↑↑↑ pCO2 ↑↑ cHCO3_ ↑s by 3,5 mmol/L for each 10 mmHg
cHCO3_ ↑ in pCO2
Respiratory Alkalosis
Acute ↓↓↓ pCO2 ↓ cHCO3_ cHCO3_ ↓ by 2 mmol/L for each 10 mmHg
↓ in pCO2
Chronic ↓↓↓ pCO2 ↓↓ cHCO3_ ↓ by 5 mmol/L for each 10 mmHg
cHCO3_ ↓ in pCO2
 A step-wise approach to
Acid-Base Status Interpretation

1. Examine the pH and comparing it to the normal range

2. Identify the primary process that led to the change in pH
3. Calculate the serum anion gap
4. Identify the compensatory process
5. Identify if any other disorder are present or there is mixed
acid-base prosess.

Example interpretation arterial blood gas analysis:

This patient has a prymary respiratory acidosis with a
compensatory metabolic alkalosis
1. Examine the pH and comparing it to the normal range

pH < 7,35 -------- > 7,45

acidemia
alkalemia
 pH

Low Normal high

No abnormality or
Acidemia mixed acid base disorder alkalemia

High pCO2 Low HCO3- Low pCO2 High HCO3-

Respiratory Metabolic Respiratory Metabolic

acidosis acidosis alkalosis alkalosis

Identifying the Primary Process

3. Calculate the serum anion gap

* Serum Anion Gap (SAG) : Na+ - ( Cl- + HCO3- )

* If this value is elevated (> 12) : elevated anion gap
* metabolic acidosis
* Normal anion gap is roughly three times the
albumin value. Albumin 4,0 g/dL = 12
 Primary and Compensatory Process
pH
Primary
process
Low Normal high

No abnormality or
Acidemia mixed acid base disorder alkalemia

High pCO2 Low HCO3- low pCO2 High HCO3-

Respiratory Metabolic Respiratory Metabolic

acidosis acidosis alkalosis alkalosis
Compensation
Metabolic Respiratory Metabolic Respiratory
alkalosis alkalosis acidosis acidosis
Case study

 A 50 year-old man came to the emergency departement after travelling.

His symptoms included persistent darrrhea (over past 3 days) and rapid
respiration (tachynea). Blood gases were drawn with the following
results.
 pH : 7,21
 pCO2 : 19 mmHg
 pO2 : 96 mmHg
 HCO3- : 7 mmol/L
 SO2 : 96%