PEM Board Review Series

Pulmonary, Renal, & Electrolytes

Nonfebrile seizures in young infants more commonly are caused by metabolic abnormalities than similar seizures in older infants and children. The most likely cause of such seizures, especially in an infant being fed a proprietary formula, is hyponatremia, which should be treated with 3 mL/kg 3% sodium chloride.

Typically, affected infants have been fed supplemental water (or another low-solute liquid) or excess water has been used in preparation of the infant's formula either intentionally (eg, due to economic hardship and being unable to provide adequate volumes of formula) or inadvertently. Water intoxication such as this and gastrointestinal losses replaced with dilute fluids are said to be the two most common causes of hyponatremia among children in the emergency department.

Symptoms of hyponatremia include altered mental status (somnolence or irritability), hypothermia, edema, and seizures. Cheyne–Stokes respirations have been reported. Although the underlying cause of the seizure is a global metabolic derangement, the seizures often are focal. It is believed that the seizures are due to a disruption in the ion gradient among neurons rather than cerebral edema because cerebral edema or other anatomic abnormalities are not found on computed tomography scan.

Immature renal function, especially the inability to excrete excess free water, is believed to contribute to the metabolic derangement for infants fed excess water. The infants frequently have relatively increased weight and once treated, show a brisk diuresis and weight loss over a short period of time. Children presenting with seizures who also have hypothermia (temperature <97.7°F [36.5°C]) often have metabolic abnormalities, including hyponatremia.

In addition, as noted previously, most children presenting with hyponatremia are experiencing fluid overload, and additional fluid therapy is not indicated. A child receiving proprietary formula only rarely presents with hypocalcemia or hypomagnesemia.

The goal of therapy is to raise the serum sodium concentration rapidly enough to stop the seizure. The administration of 3% sodium chloride at a dose of 3 mL/kg usually raises the serum sodium concentration about 3 mEq/dL (3 mmol/L), which is sufficient to end the seizure. POC testing may be used to guide electrolyte therapy, but therapy should not be delayed if hyponatremic seizures are suspected.

Further correction should be undertaken more gradually and often may be accomplished by appropriate feeding, fluid restriction in patients who are water-intoxicated, or intravenous administration of isotonic fluids. After initial stabilization, serum sodium concentrations should be normalized gradually. Too rapid correction can lead to central pontine myelinolysis. This life-threatening complication can produce neurologic symptoms that range from confusion to flaccid or spastic quadriparesis and even death.

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Often, hyponatremic seizures are resistant to treatment with standard anticonvulsant therapy. Once the sodium is corrected, additional anticonvulsant therapy typically is not required.

The age, symptoms, physical examination findings, and radiographic results described for the girl in the vignette support a diagnosis of Mycoplasma pneumoniae pneumonia. M pneumoniae is the most common cause of pneumonia in children between the ages of 5 and 15 years and usually presents with a more subacute onset and less severe symptoms than typical bacterial pneumonia. Prodromal symptoms, including myalgias, headaches, nausea, and vomiting, frequently precede the cough and respiratory symptoms by 4 to 5 days. Chest radiographic findings vary (Figures 1 and 2) and can include reticular or reticulonodular interstitial infiltrates, alveolar infiltrates with or without lobar consolidation, or a combination of alveolar and interstitial infiltrates.

 Figure 1: Radiologic features of M pneumoniae pneumonia. Bilateral pneumonia with major foci in the right upper, right middle, and left upper lobes. Reprinted with permission from Cimolai N. Mycoplasma pneumoniae respiratory infection.

Pediatr Rev. 1998;19:327-332 

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 Figure 2: Radiologic features of M pneumoniae pneumonia. Bilateral reticular

pattern with accentuated left upper lobe involvement. Reprinted with permission from Cimolai N. Mycoplasma pneumoniae respiratory infection. Pediatr Rev.

1998;19:327-332 

Hilar adenopathy and pleural effusions are seen in a small percentage of patients. Otitis media, pharyngitis, sinusitis, and rash occur in some patients. Uncommon complications of M pneumoniae infection include myocarditis, encephalitis, necrotizing pneumonia, arthritis, hepatitis, and pancreatitis.Macrolide antibiotics, including erythromycin, azithromycin, and clarithromycin, are first-line treatment of M pneumoniae infections. Doxycycline and tetracycline also are effective and can be used in children older than 9 years of age and adults. Another atypical organism, Chlamydia pneumoniae, is a common pathogen causing pneumonia in school-age children and adolescents and is susceptible to the same antimicrobials.

Oseltamivir can be considered for treatment of a documented influenza infection if the diagnosis is made within the first 48 hours of symptom onset. Viral pathogens, including influenza, respiratory syncytial virus, adenovirus, and rhinovirus, frequently are implicated as either the sole cause or coinfection in cases of pediatric pneumonia. This occurs more commonly in infants and young children; viruses are less likely to cause pneumonia in older children and adolescents. As with atypical bacterial pneumonia, viral pneumonia has an extremely variable radiographic appearance. Because this patient's symptoms began at least 5 days prior to evaluation, she would not be a candidate for oseltamivir therapy, even if influenza were identified as the causative agent.

High-dose amoxicillin is the recommended first-line agent for outpatient management of bacterial pneumonia in infants and children. Streptococcus pneumoniae is the most common causative organism in these cases. Although increasing rates of penicillin resistance have been documented with this organism, the resistance is due to an altered

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penicillin-binding protein, not beta-lactamase production, and high doses of amoxicillin can overcome such resistance. Intravenous therapy for patients requiring hospitalization can include ampicillin or a second- or third-generation cephalosporin.

Typical bacterial pneumonia usually presents more acutely with high fever, chills, focal chest pain, and lung findings as well as lobar consolidation on chest radiography.

C trachomatis pneumonia usually presents between 4 and 12 weeks of age with staccato cough, tachypnea, and diffuse rales on examination. Fever typically is absent. Radiographic findings range from normal to hyperinflation with or without diffuse infiltrates; lobar consolidation is rare. The diagnosis is confirmed by identifying C trachomatis in nasopharyngeal culture. Treatment consists of 14 days of erythromycin, 50 mg/kg per day. Limited evidence suggests that azithromycin also may be effective.

In general, infants and young children are more likely to have typical bacterial, viral, or bacterial-viral coinfection. School-age children and adolescents are more likely to have atypical bacterial infection with M pneumoniae or C pneumoniae. Identification of the specific causative organism(s), although not feasible or necessary in most cases, may be achieved through culture of blood, tracheal secretions, or pleural fluid; direct antigen detection in nasopharyngeal, blood, or urine specimens; or serologic studies. Sputum cultures are not helpful or indicated in children. In most cases, empiric therapy is guided by the most likely agent(s), based on the patient's age, presenting history, physical examination, laboratory, and radiographic findings.

HUS is a clinical diagnosis characterized by the triad of thrombocytopenia, renal impairment, and microangiopathic hemolytic anemia. Its clinical presentation and course can vary. Usually HUS occurs in previously healthy children between 6 months and 4 years of age. It is one of the most common causes of acute renal failure in children.

The causes for HUS have been divided into two categories based on clinical presentation and prognosis: diarrhea-associated (D+ HUS) and nondiarrhea-associated (D- HUS). Most cases in children are D+ HUS, associated with Shiga toxin-producing strains of Escherichia coli (STEC). O157:H7 is the most common serotype. Atypical HUS (D- HUS) occurs in only about 10% of affected children and tends to encompass a larger number of etiologic sources. Streptococcus pneumoniae and complement factor disorders are the two most common causes, but certain systemic conditions (pregnancy, malignant hypertension, malignancies), other infectious agents (human immunodeficiency virus, Epstein-Barr virus, Shigella dysenteriae type 1, Citrobacter, Campylobacter), and drugs (chemotherapeutic agents, oral contraceptives, immunosuppressants) also have been implicated. Patients who have atypical HUS tend to have no prodromal symptoms, a poorer prognosis, and a higher relapse rate.

A peripheral blood smear in HUS demonstrates normocytic normochromic anemia, with fragmented and deformed red blood cells (helmet cells, burr cells, and schistocytes) and reduced numbers of platelets. Therefore, it is the most appropriate test to help establish the diagnosis. A complete blood count typically shows an elevated white blood cell count, anemia with a median hemoglobin concentration of 8.0 g/dL (80.0 g/L) and

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hematocrit of 24% (0.24), and platelet count of 5.0 to 50.0x103/mcL (5.0 to 50.0x109/L). A corresponding elevation in the reticulocyte count occurs. Results of other hematologic studies in HUS include a negative Coombs test (with the exception of S pneumoniae-associated HUS), an increase in fibrin degradation products, and normal coagulation studies.

Stool cultures to detect E coli O157:H7 should be ordered in cases of D+ HUS, and methods for direct detection of Shiga toxin (specific antibodies and enzyme-linked immunosorbent assay) are necessary to detect non-O157:H7 STEC. Blood urea nitrogen and creatinine values are elevated, and urinalysis reveals proteinuria, hematuria, and red blood cell casts. Electrolyte abnormalities are consistent with the severity of renal dysfunction. Electrocardiography is helpful in the setting of significant electrolyte derangements, particularly hyperkalemia.

Fractional excretion of sodium is a measure of the percentage of sodium excreted in the urine compared with the sodium reabsorbed by the kidney, using the ratio of the products of urinary sodium and plasma creatinine concentration to the products of the plasma sodium and urine creatinine concentration. Such a finding is helpful to determine if the cause of acute renal failure is prerenal or intrarenal, but it is not a particularly useful ancillary study in diagnosing HUS.

Children who have typical HUS usually experience a prodrome of 2 days of nonbloody diarrhea that subsequently becomes painful and bloody. They also may have crampy abdominal pain, nausea, or vomiting. Other gastrointestinal complications that have been described include pancreatic insufficiency, intussusception, and bowel necrosis. The hemolytic anemia may manifest as pallor or jaundice. Patients may have some petechiae from the thrombocytopenia, but overt bleeding is uncommon. Fever is usually low-grade or absent. Urine output varies substantially along a spectrum from normal to complete anuria. Renal involvement also can vary from microscopic hematuria to fulminant renal failure. Most affected children have oliguria. Hypertension is common and may develop due to fluid overload or renal ischemia. Significant central nervous system symptoms are not a common feature in HUS; they usually develop after anuria. Some patients may present with seizures, ataxia, cranial neuropathies, hemiparesis, altered mental status, or coma. Central nervous system dysfunction is the predominant clinical feature in thrombotic thrombocytopenic purpura, another cause of microangiopathic hemolytic anemia.

Unfortunately, no specific treatment for HUS has proven value. Management consists of supportive therapy, with a focus on careful fluid and electrolyte management. Hemodialysis or peritoneal dialysis may be necessary in severe cases of renal failure and significant electrolyte abnormalities or fluid overload. Hypertension should be addressed with oral or intravenous medications to prevent the serious sequelae of hypertensive encephalopathy or congestive heart failure. Red blood cell transfusions may be necessary for symptomatic anemia, and platelet transfusions may be necessary prior to placement of central vascular catheters and other surgical procedures. There is no role for antibiotics in the treatment of HUS.

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The clinician examining the preschool-age child who presents with asymptomatic gross hematuria must exclude the possibility of abdominal mass in association with hematuria so as not to miss a presentation of Wilms tumor. Although this is an uncommon cause of hematuria, the limited physical examination described in the vignette does not allow exclusion of this possibility. Therefore, abdominal ultrasonography is the most appropriate next test to obtain. In contrast to patients who have microscopic hematuria, a clinically important cause generally can be identified after evaluation of most patients who have gross hematuria.

Hematuria can be categorized into glomerular and nonglomerular causes. The primary pathophysiology in glomerular causes is damage to the glomerular basement membrane, generally mediated by immunologic pathways, which allows red blood cells to pass into the urine. The most common glomerular cause in childhood is poststreptococcal glomerulonephritis with a history of antecedent pharyngitis or impetigo. Children who have poststreptococcal glomerulonephritis often present with tea-colored urine and frequently have hypertension and edema. The C3 complement titer is low in this setting, and antistreptolysin O or anti-DNAse B titers frequently are positive. Another common cause of glomerular origin is immunoglobulin A nephropathy, which is characterized by recurrent episodes of gross hematuria in association with active upper respiratory tract infection. The mean age at presentation is 9 to 10 years. For patients who have Alport syndrome (hereditary nephritis), an X-linked disorder characterized by abnormal glomerular basement membrane, a family history of nephritis or deafness often can be elicited. Quantifying the urine protein is appropriate when glomerulonephritis is suspected, but the child in the vignette does not have other symptoms typical of this condition. Benign familial hematuria is another cause of asymptomatic hematuria that likely also is related to a congenital basement membrane defect.

Among the nonglomerular causes of gross hematuria, urinary tract infection and trauma (including urethral irritation) are the most common identified in children. Renal calculi and hypercalciuria are two additional causes of hematuria, although these have a significantly lower frequency. Urinary tract infection is more common in younger girls, and local urethral trauma (of which there is no evidence in this child) is more common in boys. Hemorrhagic cystitis due to adenovirus is another cause of gross hematuria, but this patient has no other symptoms of adenoviral infection. In the setting of trauma, gross hematuria necessitates investigation with abdominal computed tomography scan.

The differential diagnosis of gross hematuria in an infant includes renal venous or arterial thrombosis due to a previously placed umbilical catheter, birth asphyxia causing corticomedullary necrosis, renal stone as a consequence of furosemide therapy for chronic lung disease, or an as yet undiagnosed hemorrhagic disorder. If abdominal swelling is present, tumor, polycystic kidney disease, ureteropelvic junction obstruction, and posterior urethral valves need to be considered.

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A:

B:

C:

D:

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E:

The Kussmaul respirations, altered mentation, and emesis described for the girl in the vignette suggests an acute acid-base disorder. Acidosis is seen frequently in critically ill patients presenting to the emergency department, and all of the pH values provided as choices are consistent with acidosis (<7.35). The predominant mechanism can be ascertained by examining the bicarbonate and PCO2 values. A low bicarbonate value suggests a metabolic process resulting from a gain in acid or loss of alkali. An elevated PCO2 points to respiratory acidosis as the primary disturbance. The lungs and kidneys primarily maintain the acid-base balance.

Metabolic acidosis prompts a compensatory increase in ventilatory drive, leading to venting of carbon dioxide. The keys to appropriate diagnosis and treatment of acidosis are to confirm the primary acid-base disorder and identify the presence of a coexisting second process (such as salicylate poisoning, sepsis, or lactic acidosis) or a metabolic alkalosis (as seen in a patient who has acidosis and substantial vomiting).

Combined results of blood gas and electrolyte determinations enable the physician to determine the underlying mechanism for the acid-base disturbance. Normal values for

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arterial blood gases are: pH of 7.4, bicarbonate of 24 mEq/L (24 mmol/L]), PCO2 of 40 torr. The next step is to calculate the anion gap (AG) (Table) and determine whether the ventilatory response is appropriate. If the decrease in PCO2 equals the decrease in bicarbonate, respiratory compensation is appropriate. Alternatively, adding 15 to the bicarbonate (when >10 mEq/L [mmol/L]) should equal the PCO2. For bicarbonate values less than 10 mEq/L (mmol/L), the expected PCO2 should equal 1.5xHCO3 + 8. An unexplained increased anion gap acidosis requires evaluation for an osmolar gap (Table). If the osmolar gap is increased, the clinician should consider toxic alcohol ingestion. 

Table: Calculations to Determine Mechanism of Acidosis 

The values in option A suggest an increased AG acidosis with appropriate respiratory compensation, as expected for the girl in the vignette, who has diabetic ketoacidosis. Increased AG acidosis is observed in the following conditions that are represented by the pneumonic MUDPILES (methanol ingestion; uremia; diabetic ketoacidosis; paraldehyde, iron or isoniazid ingestion; lactic acidosis [as in sepsis or carbon monoxide or cyanide poisoning], ethylene glycol or ethanol ingestion; and salicylate poisoning, shock, or seizures that are prolonged).

A PCO2 of 40 torr (option B) is higher than the expected value of 31 torr for the degree of metabolic acidosis (decrease in bicarbonate). Such a finding suggests a concomitant respiratory acidosis from possible early central hypoventilation, as may be seen in diabetic ketoacidosis with onset of cerebral edema.

The values in option C suggest appropriate respiratory compensation, but the AG is normal. Causes of a normal AG acidosis may be recalled by the pneumonic USED-CARP (ureterostomies, small bowel fistulas, extra chloride intake, diarrhea, carbonic anhydrase inhibitors, aldosterone deficiency, renal tubular acidosis, pancreatic fistula or drainage].

The values in option D suggest metabolic acidosis with increased AG and coexisting respiratory alkalosis, as may be seen with salicylate ingestion or sepsis. The PCO2 is lower than the expected value of 25 torr for the degree of metabolic acidosis.

The values in option E represent a primary acute respiratory acidosis. A helpful formula to calculate the expected change in pH for changes in the PCO2 is as follows: the pH rises by 0.08 for every 10-torr fall in PCO2.

The causes of metabolic acidosis can be categorized according to whether or not an elevation in the AG is present.

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The treatment of metabolic acidosis is based on the treatment of the underlying illness.

Administration of large volumes of NS can result in hyperchloremic acidosis and an artificially normal AG.

Metabolic alkalosis is a disturbance characterized by an increase in serum bicarbonate resulting from either a loss of H or a gain in bicarbonate. Respiratory compensation for metabolic acidosis is by hypoventilation.

The prototype of processes characterized by gastric acid loss is pyloric stenosis, where large amounts of gastric HCl can be lost through vomiting or NG suctioning. Hyperaldosteronism or other mineralocorticoid excess causes an increase in renal sodium absorption with secretion of H and K into the tubular lumen.

An increase in HCO3 may occur through the administration of exogenous alkali as in antacid OD, milk-alkali syndrome, large transfusions of blood with citrate anticoagulant, and parenteral therapy with acetate, lactate, or bicarbonate containing fluids. Licorice ingestion can cause a metabolic alkalosis.

The problem is that an elevated pH shifts the oxyhemoglobin dissociation curve to the left, impeding O2 delivery to the tissues. The compensatory hypoventilation from a metabolic alkalosis may worsen the hypoxemia.

Vomiting, is the most common cause in the ED of met alkalosis.

Bartter’s Syndrome is a group of 3 inherited disorders caused by dysfunction of renal ion channels. Classic Bartter’s Syndrome is caused by impaired sodium chloride reabsorption, resulting in hypokalemic metabolic alkalosis with hypercalciuria.

Eighteen hours after ingesting 20 of his mother's ferrous sulfate tablets (65 mg elemental iron per tablet), a 2-year-old boy presents to the emergency department manifesting signs of severe iron toxicity, including intractable shock.

The MOST likely arterial blood gas and chemistry results for this boy are

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1

2

11

3

4

12

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Severe iron toxicity causes a high anion gap metabolic acidosis, as indicated by the values in option 1. An anion gap [Na+ – (Cl- + HCO3

-)] of greater than 11 is considered abnormal. The anion gap of 33 for option 1 is abnormally high. The metabolic acidosis associated with iron toxicity is due, in part, to disruption of mitochondrial energy metabolism by high intracellular iron concentrations. Hepatic mitochondria, in particular, are affected.

The values in option 3 represent a normal anion gap (9) metabolic acidosis (with respiratory compensation). Severe diarrhea, with bicarbonate loss in the stool and chloride retention by the kidneys, is the most common cause of a normal anion gap metabolic acidosis in a previously healthy infant. The values in option 2 indicate a primary respiratory acidosis, those of option 4 indicate a metabolic alkalosis, and those of option 5 indicate a primary respiratory alkalosis.

High anion gap metabolic acidosis has numerous causes beyond iron toxicity, as indicated by the mnemonic MUDPILES. Additional causes include toxicity from carbon monoxide, cyanide, hydrogen sulfide, metformin, phenformin, sulfur (inorganic), theophylline, and toluene.

Normal-anion gap metabolic acidosis occurs when there is a loss of bicarbonate (either from stools, typically in acute gastroenteritis, or in urine due to renal tubular acidosis) and the body increases chloride absorption to maintain electroneutrality (thus, the anion gap is not altered). In addition, acid excretion (hydrogen) is increased in the urine, accounting for an acidic urinary pH. Decreased intravascular volume causes aldosterone secretion and a resultant sodium absorption in the kidneys in exchange for potassium

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losses. Severe cases of dehydration are associated with an increased anion gap due to production of lactic acid.

RTA Summary Points:RTA is characterized by a hyperchoremic, non-anion gap metabolic acidosis in which bicarbonate handling by the kidney is deranged. The classic presentation is of an infant who is failing to thrive.

In Type 1 (Distal) RTA, there is a failure to secrete hydrogen ion from the blood into the distal tubule, therefore, you get an acidosis in the blood and a more basic urine (pH > 5.5); hypokalemicIn Type 2 (Proximal) RTA, there is a failure to reabsorb the filtered bicarb (85% of filtered bicarb is normally reabsorbed at the proximal tubule into the blood), thus you get an acidosis but there is more time for the bicarb to get reabsorbed along the tubule so the urine pH is < 5.5; Proximal RTA rarely occurs in isolation; it often is a part of Fanconi syndrome, which is characterized by low-molecular weight proteinuria, glycosuria, phosphaturia, and aminoaciduriaType 4 RTA is due to aldosterone deficiency or aldosterone resistance that results in an inability to secrete hydrogen ions and potassium ions. Hyperkalemia distinguishes this type of RTA from the other two.

The urine anion gap sometimes is calculated to distinguish RTA from extrarenal causes. This test is based on the assumption that extrarenal losses of bicarbonate are associated with high urinary ammonia excretion, and ammonia excretion is low in patients who have RTA. The measured cations and anions in the urine are sodium, potassium, and chloride. Thus, the urine anion gap is determined via the equation: UAG= Na + K - Cl

In healthy individuals, the urine anion gap usually is near zero or is positive. Because of the increase in urinary chloride concentrations, the urine anion gap, becomes negative, ranging from -20 to more than -50 mEq/L. The negative value occurs because the chloride concentration exceeds the sum total of sodium and potassium. In contrast, if kidney function is impaired, resulting in an inability to increase ammonium excretion (ie RTA), chloride ions are not increased in the urine, the urine anion gap is not be affected, and it is positive or zero. For a patient who has a hyperchloremic metabolic acidosis, a negative urine anion gap suggests gastrointestinal loss of bicarbonate (eg, diarrhea), and a positive urine anion gap suggests impaired renal acidification (ie, RTA).

Management of RTA types 1 and 2 requires replacement of bicarbonate in the form of citric acid sodium citrate (1 mEq/mL of sodium citrate) or citric acid potassium citrate (2 mEq/mL of citrate and 2 mEq/L of potassium). Type 4 RTA requires treatment with fludrocortisone and use of orally administered potassium binders and a potassium-restricted diet.

The treatment for Laryngospasm from the placement of an oral or NP airway is succinylcholine to allow the child to be bagged and intubated. Benzos would not be helpful and could cause more laryngospasm as a side effect.

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Recent weight gain and a brisk response to diuretic therapy suggest a recent increase in total body water but a normal total body sodium, which is the cause of the hyponatremia. The most appropriate therapy for hypervolemic hyponatremia is fluid restriction. The most appropriate fluid would be isotonic saline at 2/3 the maintenance rate.

In hypertensive emergencies, Sodium Nitroprusside is a very potent vasodilator. It has an immediate onset of action and its effects are present as long as it is being infused. Labetalol can be used but its onset of action is 5 minutes and it is contraindicated in patients with asthma, heart block, or heart failure.

Renal artery stenosis is a common cause of secondary hypertension in children with history of prematurity and umbilical artery catheterization.

In management of hyperkalemia, 10% calcium gluconate should be given first to help stabilize the myocardium membrane in order to help prevent arrhythmias; Sodium bicarb, insulin (with glucose), and albuterol can be then given after the calcium gluconate has been administered. Sodium polystyrene sulfonate will clear excess potassium but will take much longer to work.

Sodium deficit= (measured sodium/1000ml) x (0.6) x fluid deficit (in ml) = sodium deficit.

In APSGN, the urinalysis is the most important study to obtain to make the diagnosis. CBC would show mild anemia, ASO titer would be elevated, demonstrating recent infection, and the C3 complement level would be decreased.

HSP presents between 2-12 years of age with arthritis/arthralgia and a papular/purpuric rash in the dependent areas of the body. Treatment is largely supportive for HSP—NSAIDS can be given for treatment of the arthralgias/arthritis; Steroids are only given to acutely ill children with severe abdominal pain, suspected renal involvement, or recurrent disease.

JRA presents with a centripetal salmon colored rash.

Mycoplasma pneumoniae typically presents with fever, generalized malaise, and non-productive cough. It has been associated with bullous myringitis.

50% of infants with pneumonia due to Chlamydia present with a history of conjunctivitis; these patients have a “staccato cough”.

Most young infants (neonates) with chlamydial pneumonia require admission to the hospital for treatment with erythromycin and observation, since it can be associated with severe mucous plugging of the airway leading to apnea and/or hypoxemia.

Children with Nephrotic syndrome have an increased risk of infection (peritonitis, cellulitis, sepsis, and meningitis—mostly due to S. pneumoniae)

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Acute Renal Failure (ARF) can cause hyperkalemia causing cardiac arrhythmias. In addition, malignant HTN leading to CHF, uremic encephalopathy, and metabolic seizures can be seen as presenting signs of ARF.

Nephrolithiasis can be due to renal stasis.

A pneumothorax is confirmed on chest x-ray. If > 10%, chest thoracostomy in the ED and admission are indicated.

In hypernatremic dehydration, you want to decrease the serum sodium levels gradually at a rate of 10 mEq/L per 24 hours in order to limit the chances of developing cerebral edema.

Children with obstructive and/or reflux nephropathy are at particular risk for developing Type IV RTA, which is characterized by a non-anion gap hyperkalemic, hyperchloremic metabolic acidosis. Type IV RTA occurs when the kidneys are resistant to aldosterone or when circulating levels are low.

Exudates occur from disease of the pleural surface due to increased capillary permeability or lymphatic obstruction. Transudates result from a change in hydrostatic pressure or osmotic pressure. The 3 criteria used (only meeting a single one is sufficient) to differentiate exudate from transudate are: 1) pleural fluid protein to serum protein ratio > 0.5; 2) Pleural fluid LDH to serum LDH ratio > 0.6; and 3) pleural LDH concentration more than 2/3 normal upper limit for serum.

When performed with thin cuts without IV contrast, CT scan is the most sensitive clinical imaging modality for calcifications.

A history of previous episodes of urolithiasis is not an indication for admission; many patients with recurrent urolithiasis are managed successfully as outpatients with oral hydration and pain control.

Any patient with CF and significant hemoptysis of 30-60 ml should be admitted to the hospital for observation. The hemoptysis is usually the result of blood vessel erosion. If it continues, Vitamin K should be given if the PT is prolonged. CF patients with massive hemoptysis (>300 ml) may develop airway compromise and consultation with a pulmonologist and thoracic surgeon should be obtained. Steroids are NOT helpful in treating hemoptysis.

Primary hyperparathyroidism is most commonly due to a solitary adenoma or as part of a hereditary syndrome (MEN). Primary hyperparathyroidism is characterized by hypercalcemia (secondary to increased bone resorption), hypophosphatemia (due to decreased reabsorption of phosphorus), and elevated Alk Phos levels ( due to induced bone turnover).

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Patients with Rhabdomyolysis will have dark urine as a result of excreted myoglobin, which will test positive for “blood” on reagent strips. Their urine, however, will NOT have increased RBC’s on microscopy. CPK is the most reliable test for confirming the diagnosis; CPK levels peak at 24-36 hours and persist for several days. CPK release occurs rapidly after muscle injury. The major complication is acute renal failure.

For bronchiolitis, only the use of supplemental Oxygen is indicated for treatment; Bronchodilators, oral steroids, and ribavirin should not be used routinely in management.

In comparison to croup, bacterial tracheitis usually presents with high fever and a systemically toxic-appearing child. The patient has a poor response to treatment with racemic epi and steroids. The illness usually presents with a longer duration of symptoms than croup. In contrast to epiglottitis, the patient with bacterial tracheitis usually has an insidious onset of symptoms, and patients can exhibit both inspiratory and expiratory stridor. The patient with bacterial tracheitis is comfortable lying flat and will not drool. Patients with bacterial tracheitis usually have an elevated WBC count. First priority in these patients is intubation and suctioning the airway, which may have purulent secretions and a pseudomembrane; Broad spectrum IV ABX given and early PICU and ENT consults. Bugs: S. aureus, S. pneumoniae, alpha-hemolytic strep, and Moraxella catarrhalis.

Disorders causing supraglottic obstruction (i.e. epiglottitis) cause stridor that is mostly heard on inspiration.

Stridor that occurs due to glottic (i.e. croup) and tracheal (i.e. tracheitis) disorders is often biphasic or heard during both inspiration and expiration.

Expiratory stridor is often due to intrathoracic obstruction.

On lat neck x-ray, to diagnose epiglottitis, the epiglottic width-to-third cervical vertebral width ratio greater than 0.5

Retropharyngeal abscesses are most common in those under age 4 since retropharyngeal lymph nodes are present at this age, often disappearing by age 4-5 years.

The classic triad of rhabdomyolysis includes myalgias, muscle weakness, and dark urine (myoglobinuria). Elevations in CK are diagnostic, not prognostic. A U/A positive for blood with the absence of RBC’s occurs. Tx=aggressive hydration, alkalinization of the urine, and adequate diuresis to prevent the development of ARF. The most devastating complication is ARF; others are hyperkalemia, hypocalcemia from deposition of the calcium in the injured tissues, both leading to arrhythmias.

For dehydration maintenance fluids, do 4 cc/kg/hr for the first 10kg, then 2 cc/kg/hr for the next 10 kg, and for the remaining weight, give 1 cc/kg/hr.

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The most common clinically evident signs and symptoms of hypokalemia are neuromuscular and cardiac. Symptoms may include muscle cramps, hyporeflexia, and weakness. More severe presentations may include bradycardia, hypotension, and arrhythmias, and respiratory muscle paralysis.

It is uncommon for children to present with a serum potassium level below 3. This degree of hypokalemia is a reasonable trigger point for pursuing a definitive diagnosis and initiating proper treatment.

In DKA, the official ADA recommendations are to hold K replacement if the K is > 5, to replace K at 30-40 in the infusing fluids, if the K is between 3.5-5 and to replace K at 40-60 in the infusing fluids if the K is between 2.5-3.5. Do 1/3 KPhos and 2/3 KCl. If the K is < 2.5, give 1 mEq/L KCl over 1 hour with insulin withheld until the K rises about 2.5. Infants receiving IV KCl should be on a cardiac monitor.

ECG findings associated with hypokalemia: Low-voltage QRS complexes Prolonged QT interval Widening of QRS complexes ST segment depression T-wave flattening or inversion U waves Ventricular dysrhythmias

The most expeditious test for assessing hyperkalemia is an ECG.

Hyperkalemia is rare in previously children who have not sustained trauma such as large burns or a crush injury, since most of the body’s K is intracellular.

Succinylcholine can causes electrolyte shifts causing hyperkalemia.

The neurologic manifestations of hyperkalemia are paresthesias and weakness.

Since renal excretion plays a key role in K levels, obtaining BUN/Cr is reasonable in cases of suspected hyperkalemia.

Treatment of Hyperkalemia depends on the underlying cause. An example of this is DKA, where the “treatment” merely is to avoid adding K to the IV fluids until the child demonstrates normal urine and the acidosis corrects itself. In another example, administering steroids to neonates with CAH should normalize the K.

For symptomatic Hyperkalemia, however, you treat with: Calcium Choride 20mg/kg or Calcium Gluconate 60 mg/kg slow IV push first to

stabilize cardiac membrane Then give Sodium bicarbonate 1-2 mEq/Kg slow IV push Give 0.5g/kg Dextrose (= 2cc/kg of D25) + 0.1 unit/kg regular insulin IV

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Give albuterol 2.5mg Neb Give Furosemide 1mg/kg IV Give Kayexalate 1 g/kg po or by retention enema Hemodialysis if last resort

Symptomatic hypocalcemia involves neuromuscular and cardiac symptoms.

Once hypocalcemia has been identified, an ionized calcium level helps in identifying the cause.

Hypocalcemia is often associated with other electrolyte abnormalities.

Calcium is the most abundant mineral in the body. 99% is in bone, and 1 % is bound to proteins or in free ionized form. Serum total calcium measures this last 1% and the “active” form is the fraction that is free ionized.

Calcium is regulated by PTH, calcitonin, and Vitamin D levels. PTH increases bone resorption which increases serum calcium. Vitamin D increases gut absorption of calcium. Calcitonin, in opposition to PTH and vitamin D, acts to lower serum calcium levels.

The most important test for calcium is an ionized calcium level. Low total serum calcium associated with a normal ionized calcium suggests hypoproteinemia due to insufficient protein production (malabsorption, hepatic disease) or excessive protein loss (nephrotic syndrome). Hypocalcemia, in which both the total and ionized calcium levels are low suggests hypoparathyroidism, vitamin D Deficiency, magnesium or phosphate abnormality, a medication effect, or an underlying disease process (malignancy, pancreatitis, sepsis). Therefore, other helpful studies include renal and hepatic function, mag, phos, and albumin levels. Radiographs may be indicated in suspected rickets, trauma, or pathologic fractures.

Common neuromuscular manifestations of hypocalcemia include paresthesias, muscle cramping, carpopedal spasm, generalized weakness, tetany, Chvostek’s sign, and seizures. Psychiatric manifestations include depression, anxiety, dementia.

Cardiac manifestations include arrhythmias, hypotension, QT prolongation, ventricular disrhythmias, and syncope.

Respiratory manifestations include laryngospasm, bronchospasm, stridor, respiratory distress, and apnea.

GI effects include abdominal distention, poor feeding, vomiting, crying, dysphagia.

The abrupt onset of respiratory symptoms after vomiting described for the neurologically compromised boy in the vignette suggests aspiration pneumonia. Little evidence is available to guide physicians in the acute management of this condition; supportive

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therapy is the treatment of choice. Airway protection is required in the presence of an ongoing risk of aspiration (continued depressed neurologic status) or impending respiratory failure, neither of which is present at this time for this patient. Suctioning the oropharynx to clear secretions or particulate matter is indicated. Corticosteroids have not been proven to be beneficial early in the course of disease, and their role in the subsequent development of pneumonia is unclear. Although approximately 50% of patients eventually develop bacterial pneumonia, presumptive use of antibiotics also has not been proven to alter the course of disease. Noninvasive ventilation is a poor choice for this boy because it is likely to distend his stomach, and with his baseline neurologic function, repeat aspiration may occur. Beta-2 agonists such as albuterol do not have a role in the treatment of aspiration pneumonia unless clinical signs of bronchoconstriction or wheezing are present.

Hypocalcemia is defined as a total serum calcium concentration less than 9.0 mg/dL (2.25 mmol/L) in children, 8.0 mg/dL (2.0 mmol/L) in term infants, and 7.0 mg/dL (1.75 mmol/L) in preterm infants. Serum calcium is regulated in a narrow range by parathyroid hormone (PTH) and calcitonin. Calcium is present in the bones, and less than 1% of the total body calcium is present in the serum and extracellular spaces. Approximately 50% is in the active or ionized form, 40% is bound to albumin, and 10% is present in the chelated form. Even minimal reductions in serum ionized calcium stimulate the calcium-sensing receptors that, in turn, trigger the release of PTH. PTH increases serum calcium concentrations by increasing renal calcium reabsorption, mobilizing bone calcium, and increasing 1,25-dihydroxyvitamin D (active form of vitamin D) that, in turn, increases renal and intestinal calcium absorption. Calcitonin is secreted in response to an elevated serum calcium concentration and reduces serum calcium by reducing bone reabsorption.

The characteristic of hypocalcemia is neuromuscular irritability, which manifests as perioral numbness, paresthesias, and muscle cramps in mild cases and carpopedal spasms and seizures in severe cases. Signs and symptoms of hypocalcemia vary along a continuum. Mild, nonspecific systemic symptoms can include vomiting, muscle weakness, and irritability. At the other end of the spectrum are life-threatening, anticonvulsant-resistant seizures; arrhythmias (QT prolongation, ST prolongation that leads to supraventricular tachycardia, complete heart block, and torsades de pointes ventricular tachycardia); and laryngospasm. Neonates may present only with nonspecific symptoms such as apnea, tachycardia, lethargy, poor feeding, vomiting, and abdominal distension. In addition, patients may show signs of underlying disease such as rachitic changes in bones due to vitamin D deficiency or resistance, dental abnormalities (failure of tooth eruption, dental hypoplasia), developmental delay (mitochondrial disorders that include mitochondrial encephalopathy, lactic acidosis and strokelike episodes [MELAS] syndrome and Kearns Sayre syndrome), or cardiac abnormalities (DiGeorge syndrome).

Evaluation of the patient in whom hypocalcemia is suspected varies according to the potential cause. Minimum studies in the emergency department should include measurements of serum calcium (total and ionized), total protein, albumin, magnesium, phosphorous, alkaline phosphatase, and creatinine; blood gas for pH; and urinary calcium and urinary creatinine assessment. Blood for assessment of serum PTH, vitamin D, PTH

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antibodies, and calcium-sensing receptor antibodies may be obtained after consultation with the endocrinologist. Serum ionized calcium values correlate with signs and symptoms of hypocalcemia and must be measured directly or calculated from the total serum calcium values after adjusting for serum albumin. As a rough estimate, the calcium concentration decreases 0.8 mg/dL (0.2 mmol/L) for every 1.0-g/dL (100-g/L) decrease in albumin concentration. Calcium binding to albumin is pH-dependent, with acidemia increasing ionized calcium concentrations and alkalosis increasing albumin binding, thus effectively reducing serum ionized calcium concentrations. For every change of 0.1 units in pH, ionized calcium changes by 10% without altering the total calcium concentration.  

Emergency management of symptomatic hypocalcemia requires administration of intravenous calcium. Suggested intravenous doses are 2-mL/kg of 10% calcium gluconate or 0.7 mL/kg of 10% calcium chloride. Each provides 20 mg/kg elemental calcium and should be administered over 10 to 20 minutes with careful monitoring for cardiac arrhythmias. Care should be taken to avoid coadministration with other solutions that result in calcium precipitation, such as sodium bicarbonate. Repeat bolus doses may be provided if the patient continues to be symptomatic. Following the bolus, calcium concentrations should be monitored and maintained either by continuous intravenous infusion (200 to 500 mg/kg per day) or via oral replacement.

Dilute urine in the face of intravascular volume depletion points to diabetes insipidus as the likely cause of hypernatremia and circulatory compromise for the child described in the vignette. Normal (0.9%) saline should be infused in the event of circulatory compromise. Subsequent rehydration should follow calculations of free water deficits and aim for correction over 48 to 72 hours. The volume needed to change an elevated serum sodium concentration is approximately 4 mL/kg of free water for each 1-mEq/L reduction in serum sodium. This should be accomplished over 48 hours. After restoring intravascular volume with normal saline, the usual rehydration fluid is 0.2% saline to 0.45% saline with 5% glucose. Care must be taken not to administer hypotonic fluid at too fast a rate because water will equilibrate across the cerebral blood-brain barrier almost immediately (long before the sodium is corrected), causing cellular edema and increased intracranial pressure.

The boy described in the vignette has severe hypercalcemia and a history of secondary urolithiasis and pathologic fracture. Initial management of symptomatic hypercalcemia consists of aggressive hydration, with initial fluid boluses of normal saline administered to correct dehydration and intravascular fluid depletion. Loop diuretics such as furosemide induce calciuresis but should be administered only after extracellular fluid volume has been restored. Thiazide diuretics such as chlorothiazide increase renal tubular reabsorption of calcium and, therefore, are contraindicated in patients who have hypercalcemia. Pamidronate is a bisphosphonate that can be used to decrease serum calcium concentrations, but it should be reserved for patients who fail initial therapy with aggressive rehydration and loop diuretics. Dialysis is rarely necessary for hypercalcemia and is reserved for severe cases or those who have failed conventional therapy. Fluid

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restriction is inappropriate in the presence of hypercalcemia.Hypercalcemia can be a manifestation of multiple endocrine neoplasia (MEN) syndrome, which can be identified through measurement of serum prolactin, growth hormone, insulin-like growth factor-1, gastrin, glucagon, calcitonin, and catecholamines. Although such assessment may be indicated in the evaluation of this patient, they are not part of the initial emergency department evaluation and management. Noncontrast abdominal computed tomography scan can be used to diagnose urolithiasis but is not indicated in the initial evaluation of the patient in the vignette.Hypercalcemia in the pediatric patient can be the result of an underlying endocrinologic disorder, medication or dietary intake, prolonged immobilization, or malignancy (Table).

Table: Causes of Hypercalcemia

• Hyperparathyroidism• Familial• Sporadic• Secondary (hyperphosphatemia, kidney transplant)• Excess Vitamin D• Dietary• Inflammatory/granulomatous diseases• Neoplastic• Bone metastases• Production of parathyroid hormone-related protein• Production of cytokines/osteoclast-activating factors• Secretion of vasoactive intestinal polypeptide• Immobilization• Familial hypocalciuric hypercalcemia• Drugs• Thiazide diuretics• Lithium• Vitamin A analogs• Calcium• Alkali• Aluminum• Hypophosphatemia• Miscellaneous

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• Hypoadrenalism• Hyperthyroidism• Juvenile rheumatoid arthritisEvaluation of the patient in whom hypercalcemia is suspected should begin with a thorough personal and family history. Findings suggesting hypercalcemia include a history of urolithiasis, pathologic fractures, and pancreatitis. Dietary history should exclude excess intake of vitamins A or D or calcium. A history of exposure to medications associated with hypercalcemia, including thiazide diuretics, lithium, and alkali, should be sought.Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder associated with hypercalcemia, hypermagnesemia, and hypocalciuria. FHH typically is asymptomatic and requires no therapy. Hyperparathyroidism (HPT) can be sporadic or familial; familial forms typically are autosomal dominant and often associated with the MEN syndrome. HPT can be diagnosed by measurement of serum parathyroid hormone (PTH), calcium, and phosphorus and urine calcium. Urine calcium values should be elevated in HPT, in contrast to the low values seen in FHH. Hormones associated with the additional endocrine abnormalities of MEN should be measured, as discussed previously.Immobilization can lead to excess boney resorption and secondary hypercalcemia; treatment should include mobilization, increased fluid intake, and avoidance of excess dietary vitamin D and calcium. Malignancy is an unusual cause of hypercalcemia in children but occasionally is seen in cases of leukemia, lymphoma, rhabdomyosarcoma, hepatoblastoma, neuroblastoma, Ewing sarcoma, or metastatic disease to bone. Malignancy-associated hypercalcemia can result from secretion of PTH-related peptide, PTH, or calcitriol or from direct invasion and destruction of bone by the tumor. Excess vitamin D concentrations can result either from excess intake or from ectopic production due to neoplasms, chronic inflammatory disorders, or granulomatous diseases. Hypervitaminosis D can be diagnosed from elevated serum and urinary calcium, low PTH, and elevated calcidiol or calcitriol concentrations.Mild degrees of hypercalcemia (<12 mg/dL [3.0 mmol/L]) are rarely symptomatic in children, and emergent treatment is unnecessary. Evaluation is aimed at identification and treatment of the underlying cause. As calcium concentrations increase, typical symptoms include anorexia, constipation, nonspecific abdominal pain, and nausea. Severe hypercalcemia (>14 mg/dL [3.5 mmol/L]) can be associated with significant neurologic symptoms that range from lethargy and poor concentration to stupor and coma. Infants may present with poor feeding leading to failure to thrive. Complications of hypercalcemia include urolithiasis, pancreatitis, pathologic fractures, gastric ulceration, and severe renal fluid losses due to impaired concentrating ability. Electrocardiography typically reveals a shortened QT interval.Treatment is indicated for any patient whose symptoms are due to hypercalcemia as well as those whose calcium concentrations are greater than 12 mg/dL (3 mmol/L). Management of symptomatic or severe hypercalcemia begins with hydration. Initial fluid boluses with normal saline should be administered to correct intravascular fluid depletion. Rehydration then should be continued with 1.5 to 2 times maintenance therapy for the first 24 to 48 hours. Hydration improves hypercalcemia by diluting intravascular calcium and promotes calciuresis by increasing glomerular filtration of calcium and decreasing renal tubular calcium reabsorption. Once intravascular volume has been restored, administration of intravenous loop diuretics

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further increases calcium excretion in the urine by inhibiting resorption of both calcium and sodium in the ascending loop of Henle.If hypercalcemia is severe or does not improve with these initial measures, medications that inhibit bone resorption by inhibiting osteoclast function can be administered. Bisphosphonate agents, including pamidronate and etidronate, are the currently used medications. They are administered by intravenous infusion over several hours, and their hypocalcemic effect can persist for days to weeks. Calcitonin can be administered subcutaneously as an adjunct to the bisphosphonates at the beginning of treatment to augment the hypocalcemic effect. Glucocorticoids can aid in decreasing serum calcium concentrations in patients who have hypervitaminosis D or malignancy-related hypercalcemia. Dialysis rarely is necessary but can be used for patients who have severe and refractory hypercalcemia.

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