Acid-base disturbances in children, Acidosis, Alkalosis

1. Description of the Problem

What every clinician needs to know

The pH of the blood is controlled via three systems: chemical buffering, respiratory function, and renal function.

Definitions

Acidosis means a clinical disturbance in which there is an increase in plasma acidity, whether due to increased production by the tissues, loss of buffering ability or decreased clearance by the kidneys. A multitude of problems, congenital and acquired, can result in metabolic acidosis. The hallmark of a metabolic acidosis is a low serum HCO₃ level.

Metabolic alkalosis means the patient has an elevated HCO₃, most typically seen with administration of loop diuretics.

A respiratory acidosis means an increase in the partial pressure of carbon dioxide in the blood (PaCO₂) due to inadequate respiration.

Respiratory alkalosis typically occurs in response to a metabolic stimulus, such as hyperammonemia (seen in urea cycle defects) or diabetic ketoacidosis (DKA).

Metabolic and respiratory mechanisms affect the acid-base state. The relationship between the pH and PaCO₂ is dependent upon the plasma bicarbonate-plasma carbonic acid pool. To estimate the effect of pH change, for every 10 mmHg PaCO₂, the pH will change by approximately 0.08; for example, if the PaCO₂ rises to 50 from a normal 40 mmHg, then the expected pH will be approximately 7.32, or decreased by 0.08.

Comparison of the base excess with the reference range assists in determining whether an acid-base disturbance is caused by a respiratory, metabolic or mixed metabolic/respiratory problem. While CO₂ defines the respiratory component of acid-base balance, base excess defines the metabolic component. To generalize, a metabolic acidosis will have a low serum HCO₃ and a respiratory acidosis will have an elevated PaCO₂, and in compensating states, as HCO₃ decreases, the physiologic response is for minute ventilation to increase and PaCO₂ to decrease, and vice versa.

When faced with a metabolic acidosis, the calculation of an anion gap will aid determining the etiology:

Anion gap (AG) = [Na⁺] – ([Cl^– ]+ [HCO₃^–]) Normal range: 3-11 mEq/L

Of note, the older calorimetric method of measurement had a normal range of 8-16 mEq/L. One should verify the normal range for your respective laboratory.

In an elevated anion gap endogenous or exogenous acids are present, whereas a normal gap means a loss of bicarbonate from the gastrointestinal tract or the kidneys either losing bicarbonate or failing to excrete H⁺. The normal gap reflects the presence of unmeasured anions such as albumin and sulphates.

Clinical features

Metabolic acidosis

The respiratory and renal systems will try to compensate for acidosis. This is manifested by an increase in respiratory rate and depth of breathing, facilitating a respiratory alkalosis to partially offset the metabolic acidosis. In extreme states of acidosis, there may be lethargy, altered mental status and cardiovascular instability.

Symptoms associated with lactic acidosis:

• Poor feeding

• Failure to thrive

• Lethargy

• Altered mental status

• Seizures

• Hypotonia

• Ataxia

• Developmental delay

• Optic nerve atrophy

• Deafness

Diabetic ketoacidosis (DKA) has as its clinical features:

• Tachypnea, hyperventilation, Kussmaul breathing

• Nausea/vomiting – due to increased β-hydroxybutyrate

• Dehydration

• Polydipsia

• Lethargy

• Polyuria, nocturia

• Acetone “fruity” breath

• Weight loss

• Altered mental status; in severe cases, coma

Inborn errors of metabolism – organic acidurias:

• Encephalopathy

• Vomiting

• Often present as neonates

Renal tubular acidosis, distal (RTA type 1):

• Elevated urine pH, greater than 5.5

• Infantile, recessive form

  Severe hyperchloremic acidosis, serum bicarbonate may be less than 10 mEq/L

  Growth retardation

  Hypokalemia

  Dehydration

  Rickets

  Nephrocalcinosis

  Hearing loss

• Adolescent form, dominant

  Nephrocalcinosis

  Mild acidosis

  Mild hypokalemia

Renal tubular acidosis, proximal (RTA type 2):

• Growth retardation

• Vomiting

• Feeding issues

• Tachypnea

• Hypophosphatemia

• Hypokalemia

• Rickets

• Muscle weaknes

Respiratory acidosis

Respiratory acidosis is due to alveolar hypoventilation, which results in an increased PaCO₂. Acute respiratory insufficiency and failure may result from lung disease, neuromuscular disease, airway obstruction or CNS dysfunction causing impaired respiratory drive.

As the PaCO₂ rises, the pH of the blood decreases; estimated as a 0.08 pH decrease for each 10 mmHg increase in PaCO₂. When the respiratory insufficiency is chronic, the kidneys compensate by holding on to plasma bicarbonate. For each 10 mmHg increase in PaCO₂ chronically, the plasma bicarbonate level will increase by approximately 3.5 mEq/L.

As PCO₂ rises, symptoms may include somnolence from hypercarbia. The acidosis may result in cardiac arrhythmias and decreased responsiveness to inotropes.

Metabolic alkalosis

Metabolic alkalosis appears in the setting of increased H⁺ losses or when exogenous buffer is administered. When assessing a patient with metabolic alkalosis, one should use the urine chloride in the evaluation.

The most common type of metabolic alkalosis encountered in the ICU is the chloride-responsive type. Patients with chloride-responsive metabolic alkalosis have a urine chloride less than 10 mEq/L. Typically this form of acid-base disturbance results from therapy with loop diuretics or thiazides. The loss of fluid secondary from Na⁺ excretion and HCO₃^– reabsorption results in a contraction alkalosis. Vomiting and prolonged NG drainage also may result in a metabolic alkalosis due to loss of HCl in gastric fluid.

Chloride-resistent metabolic alkalosis, when the urine chloride is greater than 20 mEq/L, is most commonly seen with overuse of antacids or the incorporation of excessive acetate in hyperalimentation fluids. Most commonly this is seen with overuse of antacids or the incorporation of excessive acetate in hyperalimentation fluids.

Respiratory alkalosis

Primary respiratory alkalosis is most frequently encountered in the ICU setting due to over-ambitious mechanical ventilation. Outside of that situation, the causes of respiratory alkalosis include:

• CNS: disturbances of the respiratory regulation – apneustic respirations (or agonal respirations – deep, gasping breaths with pause at full inspiration), central neurogenic hyperventilation (deep, rapid), Cheyne-Stokes respirations (oscillatory pattern of breathing of deep breathing then apnea followed again by deep breaths) due to tumor, meningitis, encephalitis, psychosis or pain.

• Hyperammonemia.

• Anxiety and panic attacks.

• Fever.

• Nicotine.

• Salicylates.

• Methylxanthines.

• Progesterone.

• Hyperthyroidism.

Signs and symptoms:

• Paresthesias.

• Dizziness.

• Headache.

• Slurred speech.

• Brief loss of consciousness due to the combination of hypocarbia-induced cerebral vascular vasoconstriction and decreased off-loading of oxygen from hemoglobin due to the Bohr effect.

• Hypokalemia.

• Hypophosphatemia.

• Hypocalcemia.

Chronic respiratory alkalosis can be diagnosed if the serum HCO₃ is below the normal range.

2. Emergency Management

Metabolic acidosis

Acidosis, whether metabolic or respiratory, warrants immediate attention. Alkalosis will allow a more measured evaluation and response.

Metabolic acidosis is generally well tolerated, but extremes can be life-threatening. Myocardial depression, arrhythmias and diminished response to inotropic agents can occur and can then result in a ever-deepening cycle of worsening acidosis. Hyperventilation, sometimes profound, is an appropriate physiologic response to acidosis.

DKA

IV fluid resuscitation. Initial resuscitation is aimed at providing adequate intravascular volume. After an initial normal saline bolus, 20 cc/kg x 1-2, fluid deficit replacement is begun with 0.9% saline.

Insulin replacement. No bolus of insulin is given. An insulin infusion is begun at 0.1 unit/kg/hr with the goal of a gradual correction of the serum glucose by 50-100 mg/dL/hr. Once the blood glucose level falls below 300 mg/dL, then dextrose should be added to the IV fluids rather than decreasing the insulin infusion.

Observation for changes in mental status indicating potential cerebral edema. If coma is present, then treatment with hypertonic saline (3% NaCl) 5 cc/kg or mannitol (0.5-1 g/kg) and monitoring of intracranial pressure (ICP) is warranted.

A recent study used MRI to determine the degree of cerebral edema in children with DKA and found that the degree of edema during DKA episodes correlated with the degree of dehydration and hyperventilation and thus cerebral hypoperfusion, and not the hyperosmolarity or osmotic changes incurred with therapy.

Management of potassium repletion. Serum potassium levels may decrease rapidly once insulin is started. Once urine flow is adequate, special attention needs to be paid to the child’s potassium. Children with hypokalemia on presentation are severely total body potassium depleted. Potassium may be given at 30-40 mEq/L as potassium chloride or phosphate.

Serum sodium. In patients with DKA, the measured serum sodium will be reduced by 1.6 mEq/L for each 100-mg/dL rise in glucose >100 mg/dL.

Monitor sodium, potassium, glucose, and pH every 2 hours until factors stabilize.

Bicarbonate is not recommended as this can lead to a paradoxical worsening of CNS acidosis.

In patients with DKA, the measured serum sodium will be reduced by 1.6 mEq/L for each 100-mg/dL rise in glucose greater than 100mg/dL. A normal or high serum sodium in a patient in DKA indicates severe free water losses. Sodium levels that fail to rise with appropriate treatment may reflect excessive free water accumulation.

Total body potassium and phosphate stores are typically depleted due to urinary losses and need to be repleted. Use of a two-bag system, one bag of 10% dextrose and another bag without dextrose, can be employed to more easily titrate the amount of glucose being infused without having to order and then wait for a new bag with a differing concentration.

Inborn error of metabolism

• Extracorporeal removal of toxic metabolite via hemofiltration or hemodialysis.

• Avoid catabolism.

• Specific emergency treatment depends upon the diesease entity. A few are below:

  Urea cycle defects:

  Arginine

  Sodium benzoate

  Sodium phenylacetate

  Sodium phenylbutyrate

  Methylmalonic aciduria – hydroxycobalamin

  Organic acidurias, fatty acid oxidation disorders: L-carnitine

  Mitochondrial disorders

  Coenzyme Q

  Carnitine

  Vitamin E

  B complex vitamins

  α-lipoic acid

Respiratory acidosis

• Positive pressure ventilation, whether invasive or non-invasive.

• Naloxone (Narcan), if history of narcotic exposure.

Metabolic alkalosis:

• Generally emergent care is not warranted and correction may be facilitated slowly.

• Intravascular volume expansion with normal saline.

• If a neonate, consider pyloric stenosis.

• Consider anti-emetics, H⁺ blockers, or proton pump inhibitors (PPI) if H⁺ losses are from GI tract.

• Discontinue or decrease diuretic therapy.

• Acetazolamide.

• Ammonium chloride.

• Potassium supplementation.

Respiratory alkalosis

• Generally, emergent care is not warranted.

• Seek diagnosis of underlying cause.

• If patient is mechanically ventilated, decrease minute ventilation by:

  Decreasing tidal volume

  Decreasing respiratory rate

  Decreasing peak inspiratory pressure

  Increasing T-high

  Increasing Hz

• Sedation or anxiolysis, if patient is agitated and hyperventilating.

3. Diagnosis

Diagnostic testing

The diagnosis of metabolic or respiratory acidosis and alkalosis may be made from a basic electrolyte profile and an arterial, or arteriolized, capillary blood gas. Once acidosis or alkalosis have been identified, additional testing will be needed to determine the etiology.

Additional testing

• Urine pH.

• Lactate.

• Glucose – elevated in DKA and hyperosmolar hyperglycemia syndrome (HHS), though pH is usually greater than 7.3 in HHS.

• Toxic substances screen – salicylates, ethylene glycol, methanol.

• Urinalysis for crystals.

• Complete blood count – to evaulate for sepsis or severe anemia.

• Liver function tests – hepatic failure may result in hypocarbia.

• Cultures, as indicated, from blood, urine, sputum, CSF.

Figure 1 shows a decision tree to determine the type of acid-base disturbance.

Figure 1.n

How do I know this is what the patient has?

Any disturbance of the acid-base status of a patient requires a comprehensive review of the acute and chronic medical conditions, medications (many have electrolyte effects, especially diuretics), and laboratory findings. The basic analysis requires a serum chemistry and blood gas. The remainder of the laboratory investigation will depend upon the intial findings.

DKA is typically diagnosed by the following:

• Presence of serum ketones greater than 5 mEq/L.

• Serum glucose greater than 250 mg/dL.

• Blood pH less than 7.3.

• Ketonuria.

• Low serum bacarbonate, less than 18 mEq/L.

• In severe cases there may be altered mental status or coma.

Renal tubular acidosis, proximal (RTA 2):

• Serum bicarbonate greater than 15 mEq/L.

• Fractional excretion of bicarbonate greater than 15% in RTA 2, when serum bicarbonate is greater than 20 mEq/L.

• Urine pH less than 5.5 when HCO₃ low.

• Fractional excretion of HCO₃greater than 15-20% during alkali therapy.

• Rickets.

Renal tubular acidosis, distal (RTA 1):

• Non-gap hyperchloremic acidosis.

• Urine pH greater than 5.5.

• Serum HCO₃ may be less than 10 mEq/L.

• Fractional excretion of HCO₃less than 10%.

• Generally hypokalemia.

• Nephrocalcinosis.

Extrarenal etilogy of acidosis:

• Elevated urine ammonium. Urine electrolytes will typically reveal [urine chloride] greater than ([urine sodium] + [urine potassium]) by approximately 50mEq/L.

Salicylate poisoning:

• Tachypnea.

• Tinnitus.

• Vertigo.

Ethylene glycol:

• Cranial nerve palsies.

Methanol ingestion:

• Retinal edema.

Other possible diagnoses

Metabolic acidosis:

• Presence of lactic acidosis may be seen in inborn errors of metabolism, including disorders of carbohydrate metabolism, electron transport and some organic acidurias. If multiple organ systems are affected, a mitochondrial oxidative phosphorylation disorder should be suspected.

• DKA may clinically appear very similarly to sepsis, toxic ingestion, acute gastroenteritis, pneumonia or urinary tract infection.

• RTA, either acquired or congenital, affects the kidney’s ability to absorb bicarbonate or excrete ammonia or an acid. In general, the anion gap is normal in these patients. RTA 1 (distal RTA) and RTA 2 (proximal RTA) are the two most common types in children.

• Ingestion.

• Thiamine deficiency, especially if child is dependent upon total parenteral nutrition without sufficient multivitamins.

Metabolic alkalosis:

• Pyloric stenosis.

• Hyperaldosteronism.

• Bartter’s syndrome.

• Liddle syndrome.

• Hyperglucocorticoidism.

• Deoxycorticosterone (DOC) excess syndrome.

• 11B-hydroxylase deficiency.

• 17-alpha-hydroxylase deficiency.

• Congenital chloride diarrhea.

• Licorice ingestion.

Respiratory acidosis:

• Narcotic use.

• Bronchitis/ bronchiolitis/pneumonia/croup.

• Asthma.

• Bronchopulmonary dysplasia – usually well compensated.

• Cystic fibrosis.

• Restrictive lung disease, such as severe scoliosis, asphyxiating thoracic dystrophy.

• Diaphragmatic hernia.

• Cystic adenoid malformation.

Respiratory alkalosis:

• Heatstroke.

• Head trauma.

• Brain tumor.

• Hyperthyroidism.

• Meningitis.

• Pneumonia.

• Salicylate ingestion.

• Methylxanthine ingestion.

Confirmatory tests

If an inborn error of metabolism is suspected, then the following should be obtained:

• Blood

  Blood gas

  Serum glucose

  Basic electrolytes

  Ammonia

  Lactate

  Pyruvate

  β-hydroxybutyrate

  Transaminases

  Coagulation profile

  Creatine kinase

  Plasma amino acids

  Plasma acylcarnitine profile

  Carnitine

  Lactate/pyruvate ratio – Normal approximately 20 mMol/L:

  Ratio less than 10 suggests pyruvate dehydrogenase deficiency.

  Ratio greater than 25 suggests tissue hypoxia, pyruvate decarboxylase deficiency, mitochondrial oxidative phosphorylation disorders.

• Urine

  Ketones

  pH

  Organic acids

  Reducing substances

  Bicarbonate

  Fractional excretion of bicarbonate greater than 15% in RTA 2, when serum bicarbonate is less than 20 mEq/L

• CSF

  Lactate

  Pyruvate

• Ophthalmologic exam

• Muscle biopsy – Useful in cases of suspected mitochondrial phosphorylation defects, looking for ragged red fibers.

4. Specific Treatment

Metabolic acidosis

Treat the underlying disorder.

In cases of extreme acidosis (pH less than 7.0), sodium bicarbonate may be given, but it must be acknowledged that this may improve or correct the acidotic state but not alter the cause of the acidosis, which may be ongoing and clinically significant.

Rapid infusions of bicarbonate are not needed and may be deleterious in certain situations. Hypernatremia may result from overzealous bicarbonate administration. Tromethamine (THAM) may also be given to buffer, especially in situations where additional HCO₃ (CO₂) load is undesirable. To achieve equivalent dosing to NaHCO₃, about three-fold more volume of THAM must be given.

Estimated bicarbonate replacement (about half should be replaced in the first few hours) = (desired HCO3 – measured HCO3) x Weight (in kg) x 0.6

In DKA, the use of bicarbonate administration is not recommended except in cases of extreme acidosis as use may exacerbate CSF acidosis and contribute to the development of cerebral edema.

RTA 2 (proximal) will respond to exogenous alkali administration. Sodium bicarbonate or citrate can be given, 5-15 mEq/kg/day. Potassium supplementation is generally needed once alkali administration is begun due to enhanced urine potassium losses. Treatment with thiazide diuretics can enhance proximal reabsorption of bicarbonate but may have the secondary effect of potassium loss.

In cases of GI losses of HCO₃, agents to slow motility may be helpful. The etiology of diarrhea should be investigated.

In cases of salicylate intoxication, use of bicarbonate can facilitate toxin elimination.

Metabolic alkalosis

Treat the underlying disorder.

Reduce or eliminate diuretic use, if clinically possible.

If vomiting or gastric loses are present, the use of anti-emetics, H₂ blockers, or proton pump inhibitors (PPI) may be beneficial.

Respiratory acidosis

Treat the underlying disorder.

If patient is mechanically ventilated, decrease effective minute ventilation by:

• Increasing tidal volume

• Increasing respiratory rate

• Increasing peak inspiratory pressure

• Decreasing T-high

• Decreasing Hz

Administer naloxone if receiving or potentially has received narcotics.

Respiratory alkalosis

Treat the underlying disorder.

If patient is mechanically ventilated, decrease effective minute ventilation by:

• Decreasing tidal volume

• Decreasing respiratory rate

• Decreasing peak inspiratory pressure

• Increasing T-high

• Increasing Hz

Treat anxiety, if present.

5. Disease Monitoring, Follow-up and Disposition

Expected response

DKA – Factors associated with an increased risk of developing cerebral edema include: younger age, longer duration of symptoms, lower pCO₂, severe acidosis, elevated BUN, failure of serum sodium to rise with therapy, treatment with bicarbonate and a higher volume of fluid resuscitation. See chapter on diabetes mellitus for specifics.

Acidosis and alkalosis are secondary findings of underlying diseases or medical conditions. Monitoring and follow up of the disease state are etiology specific. For example, children with RTA 2 can have growth retardation, rickets, osteomalacia and abnormal vitamin D metabolism but that is beyond the scope of this text ICU text.

Patient follow-up

Acidosis in general is more alarming than alkalosis and warrants close monitoring of the patient’s response to therapy. If bicarbonate has been administered, a follow-up blood gas is recommended. If a ventilator adjustment has been made, then follow up monitoring by a blood gas or measurement of end-tidal CO₂ should be done.

Pathophysiology

General

Acid-base balance is maintained by buffering of the acid load via intracellular and extracellular mechanisms, excretion of hydrogen ions in the urine, reabsorption of bicarbonate from the urine and alveolar ventilation. Metabolism of dietary carbohydrates, fats, and proteins results in the addition of acids to the blood.

Alveolar ventilation is a major contributor to extracellular buffering. CO₂, a product of fat and carbohydrate metabolism, is excreted by the lungs. Other non-volatile acids are buffered by the HCO₃^–/H₂CO₃system and CO₂ is expired.

The kidneys contribute by resorbing any filtered HCO₃ (approximately 90% in the proximal tubule via carbonic anhydrase and approximately 10% via the thick ascending limb and the medullary collecting duct) and excreting H+ via the collecting duct. Of note, urine cannot achieve a pH much less than 5.0. Phosphate and ammonia also act as buffers in the urine.

Additionally, as plasma pH decreases, the respiratory system attempts to compensate by increasing minute ventilation, which decreases PaCO₂. Therefore the respiratory system is a buffering system with limited gain as it cannot completely compensate for changes in pH due to metabolic disorders. The respiratory system is an efficient mechanism to buffer in the short term until the kidneys can manifest chronic buffering.

The kidneys have the capacity to control acid-base balance by excreting acidic or basic pH urine. Large volumes of bicarbonate and H⁺ are filtered by the kidneys and the regulation of how much is excreted versus how much is resorbed determines the net flux of the pH.

The kidneys excrete H⁺ and resorb excreted HCO3^– from the renal tubule. The filtered HCO3^– reacts with secreted H⁺via conversion by carbonic anhydrase in order to be resorbed as H₂CO₃. During periods of alkalosis, excess HCO3^– is not bound by H⁺ and gets excreted, effectively increasing H⁺ in the plasma, correcting the alkalosis.

Over time, the kidneys can completely correct for pH abnormalities. H⁺ secretion and HCO3^– reabsorption take place in all segments of the kidney, with varying efficiency, except in the thin loop of Henle.

The classification of the acid-base disorder depends upon determination of the presence of a base excess or base deficit, then eliciting the metabolic and respiratory impacts.

Metabolic

Metabolic acidosis has many etiologies. In general it can be divided into gap acidoses and non-gap acidoses. Gap acidoses result from the accumulation of organic acids (lactate, ketoacids, renal dysfunction) or the effect of toxins (methanol, ethylene glycol, salicylates, paraldehyde).

• Lactic acidosis be seen in:

  Prolonged exercise.

  Low cardiac output syndrome, shock.

  Severe dehydration.

  Hypoglycemia.

  Salicylate ingestion.

  Liver failure.

  Hypoxemia, with anaerobic metabolism.

  Seizures.

  Alcohol abuse.

  Inborn errors of metabolism, such as electron transport chain disorders, carbohydrate metabolism errors and some types of organic acidurias (proprionic acidemia, methylmalonic acidemia).

• Hyperchloremic acidosis is associated with:

  Excessive bicarbonate losses, typically from profuse diarrhea.

  RTA 2 (proximal) – bicarbonate wasting or Fanconi’s syndrome.

  Excessive administration of NaCl-containing IV fluids.

• Ketoacidosis is seen in:

  DKA – A state of relative or absolute deficiency of insulin observed in new or known diabetics. Increases in counter-regulatory hormones including glucagon, cortisol, growth hormone and epinephrine occur, resulting in hepatic gluconeogenesis, glycogenolysis and lipolysis. Lipolysis yields an increase in free fatty acids, which are used as an alternative energy source and result in an increase of ketoacid metabolites, such as beta-hydroxybutyrate, acetoacetate and acetone. Initially these ketoacids are buffered by various mechanisms, but once those mechanisms are overloaded, they spill into the urine, causing ketonuria.

  Starvation.

• RTA, several types:

  Distal.

  Proximal – RTA 2 results from defects in the proximal renal tubule’s ability to resorb bicarbonate. In the first year of life, an immature proximal tubule may result in symptoms and poor growth, which resolves with alkali administration for several years. A more common cause of RTA 2 in children is Fanconi’s syndrome, a generalized dysfunction of the proximal tubule, which may be associated with various genetic disorders or may be acquired as a result of exposure to heavy metals or certain drugs, such as aminoglycosides, ifosfamide and cisplatin.

• Ingestions:

  Salicylate (aspirin).

  Ethylene glycol (antifreeze).

  Methanol (wood alcohol).

Metabolic alkalosis occurs due to gastrointestinal loss of HCl or as a result of renal issues.

Chloride-responsive alkalosis is seen in:

• Loss of gastric fluid, typically from emesis or NG drainage.

• Diuretic-induced contraction alkalosis. Generally this is seen with use of loop diuretics and thiazides.

• Resolution of compensated hypercarbia.

Chloride-resistant metabolic alkalosis can seen in other syndromes and situations, including:

• Overuse of antacids.

• Exogenous buffer administration, such as acetate in hyperalimentation fluids.

• Hyperaldosteronism (Conn’s syndrome).

• Bartter’s syndrome – inherited defect in the thick ascending loop of Henle; associated with low potassium, hypercalcuria, polyuria, polydipsia.

• Liddle’s syndrome – rare disorder characterized by dysregulation of the epithelial sodium channel (ENaC) due to a genetic mutation causing excessive loss of potassium with sodium reabsorption in the renal tubule resulting in hypertension, hypokalemia, hypoaldosteronism

• 17-α-hydroxylase deficiency – uncommon form of congenital adrenal hyperplasia characterized by high levels of ACTH and manifested as hypertension, hypokalemia, low renin.

• Licorice ingestion – inhibition of 11-β-hydroxysteroid dehydrogenase results in hypokalemia and hypertension.

See Figure 2.

Respiratory

Respiratory acidosis

Acute respiratory acidosis may be due to airway obstruction, central nervous system depression, neuromuscular disease and acute pulmonary disease. No matter what the etiology of respiratory acidosis is, there is primary hypoventilation, which results in retention of carbon dioxide and acidosis.

Buffering of the acidotic state occurs acutely via various cellular mechanisms, including renal retention of bicarbonate. Within a few days, renal mechanisms will maximally compensate for respiratory acidosis.

Chronic respiratory acidosis is usually compensated via renal mechanisms. Causes of chronic respiratory acidosis include chronic obstructive and restrictive lung disease, neuromuscular disease, and obesity-related hypoventilation.

See Figure 3.

Respiratory alkalosis

Respiratory alkalosis results from hyperventilation, which increases exhalation of CO₂. The increased alveolar ventilation pulls CO₂ from the circulation. In an effort to maintain chemical equilibrium, circulating H⁺ and bicarbonate via carbonic anhydrase generates more CO₂, consuming H⁺and resulting in an increased pH or alkalotic state.

HCO3^– + H⁺ → H₂CO₃ → CO₂ + H₂O

Epidemiology

Metabolic acidosis

In general, metabolic acidosis can occur in any age group and has no sex or race predilection.

DKA

• Accounts for 50% of diabetes-related hospital admissions in children.

• Admission for DKA is much more common in children than adults.

Inborn errors of metabolism do have more defined ages of presentation, and race and gender predilection. Specifics are beyond the scope of this ICU text.

Metabolic alkalosis

In general, metabolic alkalosis can occur in any age group and has no sex or race predilection. It is common after cardiac surgery in children

Respiratory acidosis

In general, respiratory acidosis can occur in any age group and has no sex or race predilection.

Respiratory alkalosis

In general, respiratory alkalosis can occur in any age group and has no sex or race predilection.

Prognosis

The prognosis of any disturbance in acid-base equilibrium in a child is dependent upon the etiology. Physiologic alterations in neurologic, cardiovascular, pulmonary, gastrointestinal, renal and musculoskeletal systems can cause acid-base disequilibrium.

Complications of acidosis

• Respiratory

  Hyperventilation, tachypnea

  Dyspnea

  Respiratory muscle fatigue

• Cardiovascular

  Decreased contractility

  Arteriolar dilatation

  Venoconstriction

  Increased pulmonary vascular resistance

  Reduced splanchnic blood flow

  Decreased arrhythmia threshold

  Decreased responsiveness to catecholamines

• Central nervous system

  Obtundation

• Metabolic

  Insulin resistance

  Increased metabolic demands

  Inhibition of anaerobic glycolysis

  Hyperkalemia

  Hypercalcemia

  Reduction in synthesis of ATP

  Increased protein degradation

DKA: For children under 10, DKA causes 70% of all diabetes-related deaths.

Certain inborn errors of metabolism result in cerebral edema due to accumulation of toxic metabolites. In urea cycle defects, ammonia is not metabolized to urea and it accumulates, crossing the blood-brain barrier. In the brain ammonia is buffered by production of glutamine, but this process is rapidly overwhelmed. As brain ammonia levels rise, astrocytes swell, cerebral blood flow increases and brain ATP is depleted. Cerebral cytotoxic edema and stroke may result.

Children with RTA 2 require exogenous alkali in order to reduce the effects of acidosis on growth.

Special considerations for nursing and allied health professionals.

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What's the Evidence?

Glaser, N, Barnett, P, McCaslin, I. “Risk factors for cerebral edema inchildren with diabetic ketoacidosis. The pediatric Emergency medicineCollaborative Research Committee of the American Academy of Pediatrics”. NEJM. vol. 344. 2001. pp. 264-9.

Chua, HR, Schneider, A, Bellomo, R. “Bicarbonate in diabetic ketoacidosis – a systematic review”. Ann Intensive Care. vol. 1. 2011. pp. 23(This is a systematic analysis of the data presented in 44 studies. The authors find that there were no benefits of bicarbonate administration and it may lead to paradoxical ketosis and cerebral edema.)

Davenport, Horace W. “The ABC of Acid-Base Chemistry: The Elements of Physiological Blood-Gas Chemistry for Medical Students and Physicians”. 1974.

Glaser, N, Barnett, P, McCaslin, I. “Risk factors for cerebral edema in children with diabetic ketoacidosis. The pediatric Emergency medicine Collaborative Research Committee of the American Academy of Pediatrics”. NEJM. vol. 344. 2001. pp. 264-9. (The authors found the only significant risk factor for the development of cerebral edema in children with DKA is the use of bicarbonate.)

van Thiel, RJ, Koopman, SR, Takkenberg, JJ. “Metabolic alkalosis after pediatric cardiac surgery”. Eur J Cardiothorac Surg. vol. 28. 2005. pp. 229-33.

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