1

Plasma anion gap and diagnosis of acute metabolic acidosis in children.

Anion Gap:
1. The sum of cations and anions in ECF is always equal, so as to maintain the electrical neutrality.
Sodium and potassium together account for 95% of the cations whereas chloride and bicarbonate
account for only 86% of the anions. Only these electrolytes are commonly measured. The remaining
plasma anions (not normally measured in the laboratory) include proteins, phosphate, sulfate, urate
and organic acids.
2. Hence there is always a difference between the measured cations and the anions. The unmeasured
anions constitute the anion gap.
3. The anion gap is calculated as the difference between (Na+ + K+) and (HCO3 – + Cl–). Normally this is
about 12 mmol/liter.
4. Increase in the AG: Is most often due to increased serum lactate or acetoacetate.
5. Decrease in the AG:
a. Increase in unmeasured cations
b. Reduction in a major plasma protein such as albumin (renal loss).
Diagnosis Of Acute Metabolic Acidosis In Children
Etiology: occur via 3 basic mechanisms:
1. Loss of bicarbonate from the body
2. Impaired ability to excrete acid by the kidney
3. Addition of acid to the body (exogenous or endogenous)
Causes of metabolic acidosis:
1. Diarrhea, due to loss of bicarbonate from the body.
2. All 3 forms of renal tubular acidosis (RTA): distal (type I), proximal (type II), and hyperkalemic (type
IV).
3. Lactic acidosis:
a. Most commonly occurs when inadequate oxygen delivery to the tissues leads to anaerobic
metabolism and excess production of lactic acid.
b. Lactic acidosis may be secondary to shock, severe anemia, or hypoxemia.
4. In insulin-dependent diabetes mellitus, inadequate insulin leads to hyperglycemia and diabetic
ketoacidosis.
5. In starvation ketoacidosis, the lack of glucose leads to keto acid production,
6. Renal failure causes a metabolic acidosis because of the need for the kidneys to excrete the acid
produced by normal metabolism.
7. Salicylate intoxication is now much less common because aspirin is no longer recommended for
fever control in children.
8. Many inborn errors of metabolism cause a metabolic acidosis.
Diagnosis of acute metabolic acidosis:
History and Physical Examination
1. History should be first evaluated in a child with metabolic acidosis. The clinical context will often point to the
underlying disorder leading to metabolic acidosis.
2. For example, metabolic acidosis in a child with severe diarrhoea suggests an acute HCO3– loss through the
gastrointestinal tract, while recent-onset polyuria, polydipsia, weight loss, and hyperglycaemia suggest new-
onset diabetes with ketoacidosis.
Laboratory Evaluation
1. A diagnostic evaluation that includes serum electrolytes, blood glucose, renal function tests, serum lactic acid,
serum anion gap (SAG), and urine anion gap usually sufficient.
 2

2. In some cases, a blood gas measurement is needed to differentiate primary metabolic acidosis from
compensated respiratory alkalosis.
Blood Gas
1. If the patient’s pCO2 is within the predicted range, then there is no additional respiratory
disturbance. If the pCO2 is greater than expected, this indicates an additional respiratory acidosis. If
the pCO2 is less than expected, there is an additional respiratory alkalosis occurring.
2. Anion Gap:
a. Once metabolic acidosis has been confirmed, serum electrolyte values are used to calculate the SAG.
The AG further divides patients into two groups: those with normal AG metabolic acidosis and those
with increased AG metabolic acidosis.
b. Increased anion gap metabolic acidosis
i. Increased AG metabolic acidosis occurs when there is an increase in the number of both
H+ and unmeasured anions. For example, in diabetic ketoacidosis (DKA), β-hydroxybutyrate
and acetoacetate are the unmeasured anions. In lactic acidosis, lactic acid is composed of
negatively charged lactate ions and positively charged H+.
3. Osmolar Gap
a. The metabolites of certain toxic alcohols and glycols can generate a high AG metabolic acidosis. The
accumulation of these alcohols, because of their low molecular weight, substantially elevates the serum
osmolality and causes a disparity between the estimated and measured serum osmolality.
b. An elevated serum osmol gap suggests acidosis is due to components such as methanol or ethylene
glycol.
4. Delta ratio
a. This Delta Ratio is sometimes useful in the assessment of metabolic acidosis. The Delta
Ratio is defined as:
Delta ratio = (Increase in Anion Gap / Decrease in bicarbonate)
b. If the delta ratio is very low (less than 0.4) then it supports the diagnosis of a normal anion
gap acidosis. If the delta ratio is high (greater than 2) then it suggests that the bicarbonate
was high prior to the onset of the acidosis (as seen in compensated respiratory acidosis). A
ratio between 0.4 and 2.0 suggests a mixed picture.
Basic laboratory tests:
1. Basic laboratory tests for a child with a metabolic acidosis should include measurements of
electrolytes, blood urea nitrogen (BUN), creatinine, and serum glucose levels, as well as a urinalysis.
2. Elevated BUN and creatinine = renal insufficiency
3. elevated BUN : creatinine ratio (>20 : 1)= prerenal azotemia
4. Metabolic acidosis, hyperglycemia, glycosuria, and ketonuria= diabetic ketoacidosis.
5. metabolic acidosis and hypoglycemia = Adrenal insufficiency
6. Metabolic acidosis, normoglycemia, and glycosuria= type II RTA
7. Increased serum potassium with acidosis: renal insufficiency;
8. metabolic acidosis, hyperkalemia, and hyponatremia = aldosterone deficiency

Outline the algorithmic approach to metabolic alkalosis in children.

Definition
Metabolic alkalosis has been defined as any condition wherein:
1. Plasma pH is above 7.45, with normal or high Pco2 and TCO2 (total CO2) greater than 32 mM.
2. Base excess (BE) is greater than 2 mM (normal range -2 to +2 mM).
3. Metabolic alkalosis-Aue to an increase in bicarbonate.
4. Respiratory alkalosis-due to a decrease in carbonic acid.
 3

Causes of Metabolic alkalosis

(1) An inherited condition
a. Gitelman’s syndrome,
b. Bartter’s syndrome,
c. Congenital chloride-losing diarrhea,
d. Cystic fibrosis,
e. Liddle’s syndrome,
f. Apparent mineralcorticoid excess (ame),
g. Glucocorticoid remediable hypertension [gra], and the
h. 11- or 17-Beta OH deficient variants of congenital adrenal hyperplasia [CAH]);
(2) Acquired disease
a. Gastroenteritis,
b. Bulemia,
c. Anorexia,
d. Cushing’s syndrome,
e. Nephrotic syndrome,
f. Liver disease and
g. Hyperaldosteronism
(3) Drugs, surgery, medication or other treatments
a. Thiazide or loop diuretics,
b. Laxatives,
c. Fludrocortisone,
d. Milk-alkali syndrome,
e. Short bowel syndrome,
f. Penicillin,
Evaluation:
1. The evaluation of metabolic alkalosis starts with measurement of the urinary chloride level.
2. If the urinary chloride level is low (less than 20 mEq/L), the metabolic alkalosis is most likely the
result of a volume-responsive condition. Volume resuscitation with saline typically leads to
resolution.
3. If the urinary chloride level is high (greater than 20 mEq/L), measure the patient's blood pressure.
4. If the patient is hypertensive, the differential diagnosis includes:
a. Aldosterone excess (an aldosterone-to-renin ratio greater than 20:1 indicates primary
hyperaldosteronism).
b. Cushing syndrome, which involves excess cortisol.
c. Liddle syndrome, which is characterized by a renal tubular sodium channel defect that
results in excess sodium reabsorption and potassium wasting; the resultant volume
expansion also suppresses renin and aldosterone.
d. Hydroxylase deficiencies (rare); signs and symptoms may include hirsutism and
clitoromegaly, decreased renin and aldosterone levels, and (usually) hypertension; elevated
levels of 17-ketosteroids and dihydroepiandrosterone sulfate are diagnostic.
e. Diuretic use, which produces elevated renin and aldosterone levels.
f. Renal artery stenosis, which results in elevated renin and aldosterone levels.
g. Renin-secreting tumors, which result in an increase in the aldosterone as well as the renin
level.Measurement of renin and aldosterone levels can help narrow the differential.
5. If the patient is normotensive and has metabolic alkalosis and a high urinary chloride level, the
differential diagnosis includes:
 4

a. Bartter syndrome (not a single disorder), which is characterized by hypokalemia, metabolic

alkalosis, and elevated renin and aldosterone levels. (Patients who have classic Bartter
syndrome, which occurs during early childhood, also have increased urinary prostaglandin
excretion and normal urinary calcium excretion; rarely, this condition is associated with
hypomagnesemia.)
b. Gitelman syndrome (a variant of Bartter syndrome), which is often associated with low
serum magnesium levels, normal prostaglandin excretion, and decreased urinary calcium
excretion.
c. Villous adenoma (unlikely if diarrhea is not present).
d. Diuretic use.

Describe the etiology and pathophysiology of hyponatremia in children.

Pathophysiology:
1. Hyponatremia is defined as a serum sodium level of less than 135 mEq per L. Severe hyponatremia
(serum sodium level less than 125 mEq per L)
2. Plasma osmolality has a role in the pathophysiology of hyponatremia. Changes in serum osmolality
are determined by changes in the serum concentration of sodium and its associated anions.
3. The major mechanisms responsible for regulating water metabolism are thirst and the pituitary
secretion and renal effects of vasopressin.
4. Thirst mechanism:
a. Hyponatremia results from the inability of the kidney to excrete a water load or excess water
intake. Water intake depends upon thirst mechanism. Thirst is stimulated by increase in
 5

osmolality. Thirst is sensed by osmoreceptors located in the hypothalamus and leads to the
release of anti-diuretic hormone (vasopressin) from the posterior pituitary.
b. Antidiuretic hormone acts on the V2 receptors located at the basolateral aspect of the
collecting duct cells and leads to increased aquaporin expression on the luminal aspect of
the collecting duct cells which increases water absorption and abolishes thirst.
5. Release of Arginine vasopressin (ADH)
a. Arginine vasopressin (ADH) is produced in the hypothalamus and released from the
posterior pituitary.
b. Osmoregulation of ADH: Osmoreceptive neurons located in the anterior hypothalamus
detect changes in systemic osmolality. This leads to both increased release of vasopressin
from the pituitary gland. Vasopressin in turn increases the re-absorption of water from the
urine in the distal tubules of the nephron, which leads to urine that is more concentrated.
c. Baroregulation of ADH: Stretch-sensitive receptors in the left atrium, carotid sinus and aortic
arch sense circulating volume. When the circulating volume is increased, afferent neural
impulses inhibit the secretion of vasopressin. Conversely, when the volume is decreased, the
discharge rate of the stretch receptors slows and vasopressin secretion increases.
6. Renal regulation:
a. ADH increases water absorption by increasing the permeability to water in the collecting
tubule.
b. The renin-angiotensin system acts by controlling renal reabsorption of sodium and
determines the extracellular fluid volume.
Classification of hyponatremia:
The most common classification system for hyponatremia is based on volume status:
a. Hypovolemic (decreased total body water with greater decrease in sodium level),
b. Euvolemic (increased total body water with normal sodium level), and
c. Hypervolemic (increased total body water compared with sodium).
Hypovolemic hyponatremia:
1. Gastrointestinal (emesis, diarrhea)
2. Skin sweating or burns
3. Third space losses
4. Renal losses
a. Diuretics
b. Polyuric phase of acute tubular necrosis
5. 21-hydroxylase deficiency
EUVOLEMIC HYPONATREMIA:
1. Syndrome of inappropriate antidiuretic hormone
2. Desmopressin acetate
3. Glucocorticoid deficiency
4. Hypothyroidism
5. Water intoxication
6. Iatrogenic (excess hypotonic intravenous fluids)
7. Feeding infants excessive water products
HYPERVOLEMIC HYPONATREMIA:
1. Congestive heart failure
2. Cirrhosis
3. Nephrotic syndrome
4. Renal failure
 6

5. Capillary leak due to sepsis

6. Hypoalbuminemia due to gastrointestinal disease (protein-losing enteropathy
PSEUDOHYPONATREMIA:
7. In patients with elevated serum lipids or proteins, the water content of the serum decreases
because water is displaced by the larger amount of solids.
8. When the solid component increases, there is a decrease in the sodium concentration per liter of
serum, despite a normal concentration of sodium when based on the amount of sodium per liter of
serum water.
9. The most common etiology is hyperglycemia, such as during diabetic ketoacidosis.
 7

Regulation of calcium metabolism and its role of vitamin D in calcium homeostasis.

Calcium Distribution:
1. Total body calcium is 1-1.5 kg; 99% in bone and 1% in ECF. The extracellular fluid contains
approximately 22.5 mmol, of which about 9 mmol is in the serum.
2. In serum, calcium exists in 3 forms:
a. Protein-bound: about 40% of serum Ca (4-5mg/dl) is bound to proteins, mostly albumin
and, to a lesser extent, globulin.
b. Ionized (free): About half of this (5 mg/dl) is in the ionized form which is functionally the
most active.
c. Complexed (chelated). 1 mg/dl serum Ca is found in association with citrate and/or
phosphate.
d. The total concentration of plasma or serum Ca is 9-11 mg/dl.
Absorption:
1. Absorption is from I and II part of duodenum. It is absorbed against concentration gradient and
requires energy. Absorption requires carrier protein and calcium dependant ATPase.
2. Factors increasing absorption:
a. Vit. D induces synthesis of Ca binding protein (Calbindin) in intestinal epithelial cells and thus
facilitate absorption.
b. Parathyroid hormone increases calcium transport from intestinal cells.
3. Factors decreasing absorption:
a. Phytates in food and oxalates in leafy vegetables form insoluble salts and interfere with Ca
absorption
b. Malabsorption syndromes: unabsorbed fatty acid form insoluble calcium salt.
c. Phosphate precipitate Ca.
d. Alkaline pH in GIT
e. High content of dietary fiber.
Regulation of plasma calcium:
1. The hormones calcitriol, parathyroid hormone (PTH) and calcitonin are the major factors that
regulate the plasma calcium within a narrow range of 9-11 mg/dl.
2. Regulation depends on:
a. Three Calcitropic hormones
a. PTH
b. 1,25 (OH) Vit.D
c. Calcitonin
 8

b. Three target organs:

a. Bone
b. Gut
c. Kidney
c. Three bone cells
a. Osteoblasts
b. Osteocytes
c. Osteoclasts
Role of VIT.D in Ca Homeostasis:
Activation of Vitamin D:
1. Liver: The cholecalciferol is first transported to liver, where hydroxylation at 25th position occurs, to
form 25-hydroxy cholecalciferol (calcidiol). The hepatic 25-hydroxylase is a microsomal
monooxygenase. It requires cytochrome P-450 and NADPH. 25-HCC is the major storage form.
2. Plasma: 25-HCC is bound to "vitamin D binding protein" (VDBP), an alpha-2 globulin.
3. Kidney: In kidney, it is further hydroxylated at the 1st position to form 1,25-dihydroxy
cholecalciferol. Since it contains three hydroxyl groups at 1, 3 and 25 positions, it is also called
Calcitriol. It is the active form of vitamin.D
Biochemical Effects of Vitamin D: The sites of action are:
1. GIT-intestinal villi cells
2. bone osteoblasts
3. kidney distal tubular cells.
GIT:
1. Calcitriol promotes the absorption of calcium and phosphorus from the intestine. Calcitriol binds
with a cytosolic receptor to form a calcitriol-receptor complex. This complex then approaches the
nucleus and interacts with a specific DNA leading to the synthesis of a specific calcium binding
protein. Calcium uptake is enhanced by Calbindin.
Effect of Vitamin D in Bone:
1. In the osteoblasts of bone, calcitriol stimulates calcium uptake for deposition as calcium
phosphate
2. Calcitriol stimulates osteoblasts which secrete alkaline phosphatase. Due to this enzyme, the
local concentration of phosphate is increased. The ionic product of calcium and phosphorus
increases, leading to mineralization.
3. Along with PTH it mobilizes Ca and phosphates from the bone to maintain their plasma level
also.
Effect of Vitamin D in Renal Tubules:
1. Calcitriol increases the reabsorption of calcium and phosphorus by renal tubules, therefore both
minerals are conserved (PTH conserves only calcium) bone.
2. Kidney converts 25, Hydroxy cholecalciferol to 24,25 - DHCC an inactive form instead of 1-25-
DHCC when Vit D is available in plenty so that its biological action is kept optimum levels.
 9

Sodium metabolism and hypernatremia in children.

Sodium metabolism
Body Content and Physiologic Function
1. Sodium is the dominant cation of the ECF, and it is the principal determinant of extracellular
osmolality. Sodium is therefore necessary for the maintenance of intravascular volume.
2. Less than 3% of sodium is intracellular. More than 40% of total body sodium is in bone; the
remainder is in the interstitial and intravascular spaces.
Intake
1. A child’s diet determines the amount of sodium ingested. An occasional child has salt craving
because of an underlying salt-wasting renal disease or adrenal insufficiency. Children tend to have
very high sodium intakes because their diets include a large amount of “junk” food or fast food.
Infants receive sodium from breast milk (≈7 mEq/L) and formula (7-13 mEq/L, for 20 calorie/oz
formula).
2. Sodium is readily absorbed throughout the gastrointestinal tract. The presence of glucose enhances
sodium absorption owing to the presence of a cotransport system.
Excretion
1. Sodium excretion occurs in stool and sweat, and the kidney regulates sodium balance and is the
principal site of sodium excretion.
2. Sweat sodium concentration is increased in children with cystic fibrosis, aldosterone deficiency, or
pseudohypoaldosteronism. The higher sweat losses in these conditions may cause or contribute to
sodium depletion.
3. When the sodium concentration increases, it causes increased thirst and increased secretion of ADH,
which leads to renal conservation of water to increase the water content of the body, and the
sodium concentration returns to normal.
4. The plasma volume determines the amount of sodium in the urine. This is mediated by the renin–
angiotensin–aldosterone system.
Hypernatremia:
Hypernatremia is a sodium concentration >145 mEq/L, although it is sometimes defined as >150
mEq/L
Causes:
Water deficit:
Nephrogenic diabetes insipidus
Water and sodium deficits:
Gastrointestinal losses
Diarrhea
Emesis/nasogastric suction
Osmotic cathartics (lactulose)
Cutaneous losses
Burns
Excessive sweating
Renal losses
Osmotic diuretics (mannitol)
Diabetes mellitus
Chronic kidney disease (dysplasia and obstructive uropathy)
Polyuric phase of acute tubular necrosis
Clinical Manifestations
 10

1. Doughy feel of the skin,

2. Woody consistency of the tongue,
3. Alteration in sensorium,
4. Patients are irritable, restless, weak, and lethargic.
5. Some infants have a high-pitched cry and hyperpnea
6. Seizures, and
7. Intracranial bleeds: Patients may have subarachnoid, subdural, and parenchymal hemorrhage.
8. Thrombotic complications occur in severe hypernatremic dehydration; they include stroke, dural
sinus thrombosis, peripheral thrombosis, and renal vein thrombosis. This is secondary to
dehydration and possibly hypercoagulability associated with hypernatremia.
Diagnosis
1. In hyperaldosteronism, hypernatremia is associated with hypertension, hypokalemia, and metabolic
alkalosis.
2. In nephrogenic diabetes insipidus, the urine is inappropriately dilute and urine volume is not low.
Measurement of ADH and a water deprivation test, including a trial of desmopressin acetate will
differentiate between nephrogenic diabetes insipidus and central diabetes insipidus.
Management:
1. Mild hypernatremia:
a. Administration of ORS in conscious patients.
b. Free water or breast feeds should be offered to the child.
2. Severe hypernatremia:
a. Most dangerous form of dehydration
b. Rapid treatment of hypernatremic dehydration may cause cerebral edema, seizures, brain
herniation and death.
c. Serum sodium concentration should not decrease by >12 mEq/L every 24 hr. The deficits in
severe hypernatremic dehydration may need to be corrected over 2-4 days.
3. Phase I: Restore intravascular volume: Normal saline: 20 mL/kg over 20 min (repeat until
intravascular volume restored)
4. Phase II: Determine time for correction on basis of initial sodium concentration:
[Na] 145-157 mEq/L: 24 hr
[Na] 158-170 mEq/L: 48 hr
[Na] 171-183 mEq/L: 72 hr
[Na] 184-196 mEq/L: 84 hr
5. Fluid:
a. Typical fluid: 5% dextrose + half-normal saline (with 20 mEq/L KCl unless contraindicated)
b. Typical rate: 1.25-1.5 times maintenance
6. If the serum sodium concentration is more than 200 mEq/L, peritoneal dialysis should be performed
using a high-glucose, low-sodium dialysate.

Pathophysiology of body fluid volume and its clinical applications.

Total Body Water
1. Total body water (TBW) varies with age. During the 1st yr of life, TBW decreases to approximately
60% of body weight and basically remains at this level until puberty.
2. At puberty, the fat content of females increases more than that in males, who acquire more muscle
mass than females. Because fat TBW in females decreases to approximately 50% of body weight.
3. TBW is distributed as follows:
a. Intracellular fluid 40%
 11

b. Extracellular fluid 20%

i. Intravascular 5%
ii. Interstitial fluid 15%.
c. The ECF volume is approximately 20-25% of body weight, and the ICF volume is
approximately 30-40% of body weight.
d. Transcellular fluid, refers to fluid in areas such as cerebrospinal, synovial, intrapleural, and
gastrointestinal system.
Movement of fluid between compartments
1. Fluid is separated into compartments by semipermeable membranes. The membranes are highly
permeable to water but require energy to transport ions.
2. Distribution of fluid between intracellular and extracellular compartments is determined by the
concentration of Na+, chloride Cl–), and other electrolytes.
3. Water moves between compartments following osmotic gradients. A change in the relative
concentration of solute or water will cause water to shift between compartments.
Fluid regulation:
1. The major mechanisms responsible for regulating water metabolism are thirst and the pituitary
secretion and renal effects of vasopressin.
2. Thirst mechanism:
a. Water intake depends upon thirst mechanism. Thirst is stimulated by increase in osmolality.
Thirst is sensed by osmoreceptors located in the hypothalamus and leads to the release of
anti-diuretic hormone (vasopressin) from the posterior pituitary.
b. Antidiuretic hormone acts on the collecting duct cells which increases water absorption and
abolishes thirst.
3. Release of Arginine vasopressin (ADH)
d. Arginine vasopressin (ADH) is produced in the hypothalamus and released from the
posterior pituitary.
e. Osmoregulation of ADH: Osmoreceptive neurons located in the anterior hypothalamus
detect changes in systemic osmolality. This leads to both increased release of vasopressin
from the pituitary gland. Vasopressin in turn increases the re-absorption of water from the
urine in the distal tubules of the nephron.
f. Baroregulation of ADH: Stretch-sensitive receptors in the left atrium, carotid sinus and aortic
arch sense circulating volume. When the circulating volume is increased, afferent neural
impulses inhibit the secretion of vasopressin. Conversely, when the volume is decreased, the
discharge rate of the stretch receptors slows and vasopressin secretion increases.
4. Renal regulation:
c. ADH increases water absorption by increasing the permeability to water in the collecting
tubule.
d. The renin-angiotensin system acts by controlling renal reabsorption of sodium and
determines the extracellular fluid volume.
Clinical applications:
Dehydration:
1. Mild: loss of 5% of body weight
2. Moderate: loss of 7.5% of body weight
3. Severe: loss of 10% of body weight
Types:
1. Isonatremic dehydration or isotonic or iso-osmolar dehydration. Serum Sodium 135-145 meq/L
2. Hypernatremic dehydration or hypertonic or hyperosmolar dehydration.> 145 Meq/L
 12

3. Hyponatremic or hypotonic or hypo osmolar dehydration. < 135 Meq/L

Causes
1. Severe diarrhea and vomiting due to gastrointestinal disorders
2. Excess urinary output due to renal disorders
3. Excess loss of water through urine due to endocrine disorders such as diabetes mellitus, diabetes
insipidus and adrenal insufficiency
4. Insufficient intake of water
5. Prolonged physical activity without consuming adequate amount of water in hot environment
6. Excess sweating leading to heat frustration (extreme loss of water, heat and energy). Severe
sweating and dehydration occur while spending longer periods on regular basis in the saunas
7. Use of laxatives or diuretics.

Etiology and management of hypokalemia

Hypokalemia is defined as serum potassium concentration < 3.5 mEq/l.
Pseudohypokalemia is seen when blood samples containing very high number of white blood cells as the
result of K+ uptake by white blood cells. This is seen in acute myelogenous leukemia (AML).
Etiology:
1. Intracellular potassium shift
a. Insulin and β2 receptors agonists (such as epinephrine, albuterol, and ephedrine) are the major
causes of intracellular K+ shift.
b. Redistribution is seen in hypokalemic periodic paralysis. This is a rare disorder seen more
commonly in association with thyrotoxicosis
c. The antipsychotic medications risperidone and quetiapine can rarely cause intracellular K+ shift.
2. Non-renal potassium loss
a. The most common causes are diarrhea, vomiting, nasogastric (NG) suctioning, and laxatives.
b. Hypokalemia due to K+ loss via excessive perspiration is uncommon.
3. Renal potassium loss
a. Diuretics cause of hypokalemia due to increased distal flow and secondary hyperaldosteronism
resulting from volume depletion.
b. Aldosterone is the main K+ regulating hormone and excess aldosterone as in primary
aldosteronism leads to hypokalemia.
c. In 11β-hydroxylase deficiency an 17α-hydroxylase deficiency, the value of 11-
deoxycorticosterone is elevated, causing variable hypertension and hypokalemia.
d. In cystic fibrosis, there is chloride loss in sweat and in congenital chloride-losing diarrhea, an
autosomal recessive disorder, there is high stool loss of chloride, leading to metabolic alkalosis.
The kidney compensates for the metabolic alkalosis by excreting bicarbonate in the urine, with
obligate loss of potassium and sodium with the bicarbonate.
e. Magnesium deficiency may result in refractory hypokalemia. Magnesium inhibits ROMK
channels, subsequently hypomagnesemia increases potassium secretion in the collecting duct.
f. Both proximal and distal renal tubular acidosis cause hypokalemia due to renal K+ loss.
g. Renal K+ loss is also seen in certain rare disorders such as Bartter’s syndrome, Gitelman’s
syndrome, and Liddle’s syndrome.
h. Inadequate intake: patients on total parenteral or enteral nutrition, anorexia, and starvation.
Treatment
1. Patients with serum K+ in the range of 3.0-3.5 mEq/l are usually treated with oral K+ salts as long as
they can take oral medications. Liquid preparations are bitter tasting; microencapsulated or wax
 13

matrix formulations are less irritating than tablets to the gastric mucosa , Oral dose: 2-4 mEq/kg/day
with a maximum of 120-240 mEq/day in divided doses.
2. Patients with serum K+ < 3 mEq/l require IV K+ especially in emergencies such as arrhythmias. IV
replacement should be cautious. The dose of intravenous potassium is 0.5-1.0 mEq/kg, usually given
over 1 hr. The adult maximum dose is 40 mEq. Conservative dosing is generally preferred.