Laboratory Investigations:
Arterial blood gases:↓pO2, ↑pCO2: respiratory center depression, aspiration pneumonia, pulmonary edema
Plasma electrolytes - potassium:
Hypokalemia
normal:
3.5 - 5 mE/L
- β2 agonists, caffeine, theophylline → ↑cAMP →↑ NaK-ATPase activity.
- Diuretics that ↑K+ loss into urine (loop diuretics and thiazides).
- Toluene (unknown mechanism; causes extreme muscle weakness)
- Barium (Ba2+ blocks K+ channels in the membrane of excitable cells → ↓K+ efflux
Hyperkalemia
- β blockers →↓cAMP →↓NaK-ATPase activity.- Digitalis, fluoride (inhibits NaK-ATPase) and lithium.
- Rhabdomyolysis (e.g., after convulsion), hemolysis (e.g., arsine intoxication)
Plasma electrolytes-Anion-gap: calculated from plasma Na+, K+, HCO3- and Cl- levels
Calculation(Na+ + K+) (Cl- + HCO3-) NORMAL VALUE: <12 mE/LIncreased
anion
gapOccurs when an acid accumulates in the blood and causes a decrease in HCO3- concentration. The acid protonates HCO3- and thus H2CO3 is formed, which is converted into CO2 and H2O by carbonic anhydrase.
Examples:
- aspirin, isoniazid, iron; methanol, ehtylene glycol intoxication.
- drug-induced seizure (causes lactic acidosis).
Diff. diagnosis: shock-induced lactic acidosis, diabetic ketoacidosis
Plasma osmolality (Posm), osmolal gap:
Posm can be * measured or * calculated.
Measured PosmObtained by Freezing Point Depression OsmometerCalculated Posm= 2 x plasma [Na] + [glucose] + [BUN]Osmolal gap= MEASURED Posm CALCULATED Posm
(NORMAL VALUE: <10 units)Iincreased
osmolal gapOccurs when large amounts of an osmotically active compound accumulate in the blood.
Examples: ethanol, isopropanol, methanol, ethylene glycol intoxication
Osmolality is a measure of the osmoles (Osm) of solute per kilogram of solvent (Osm/kg), osmolarity is the number of osmoles of solute per liter (L) of solution (Osm/L).
Freezing-point depression is the decrease of the freezing point of a solvent on addition of a non-volatile solute. Examples include salt in water, alcohol in water. The radiator fluid in an automobile is a mixture of water and ethylene glycol.
Laboratory tests for renal function:
BUN, serum creatinine: their elevation indicates ↓ in the GFR; caused by nephrotoxic drugs and shockOxalate crystals in urine sediment: caused by ethylene glycol (converted into oxalic acid → Ca-oxalate)
Pinkish color of urine: phenothiazine intoxication
Ketonuria without metabolic change: isopropyl alcohol and acetone intoxication
ketonuria with metabolic acidosis: salicylate poisoning
Laboratory tests for hepatic function:
↑ serum ALT, AST (indicate hepatocellular injury)↑ serum GGT, AP (indicate cholestasis)
Instrumental examinations:
ECG Bradycardia, AV block: beta receptor blockers
Extreme bradycardia, PQ prolongation or AV block, ventricular arrhythmias: digitalis
Widening of QRS (>0.1 sec): tricyclic AD, carbamazepine, quinidine, amantadine, Ca-channel blockers
QT prolongation (indicate delayed repolarization): phenothiazines, fluorokinolones, Ca-channel blockers, As
Ischemic changes (ST elevation): carbon monoxide (hypoxia), cocain
Endoscopic examination: obligatory after corrosive ingestion (e.g., acids, bases)
To determine if gastric surgery is needed or not (perforation?)
Do not be afraid, the gastroscop does not cause perforation in the hand of an expert!
X-ray examination
Abdominal X-ray: radiopaque toxins such as iron-containing pills, enteric-coated tablets, heavy metals can be visualized Chest X-ray: may reveal aspiration pneumonia and pulmonary edema
CT scan: when head trauma is suspected (intracranial hemorrhage?)
Analysis of the toxicant:
a. Qualitative analysis (screening) for unknown toxicants from urine or blood to answer the question:What may have caused the intoxication?
1. Rapid screening tests using special kits and one-step analysis used for:
- street drugs and common hypnotics
These typically detect:
morphine, methadone, barbiturates, benzodiazepines, amphetamine, cocaine, cannabinoids from urine.
- paracetamol and salicylate from a few drops of blood: (a one-step immunoassay)
2. Screening tests for a wider range of compounds:
- TLC analysis
- Special HPLC analysis: for identification of 450 drugs (except paracetamol, aspirin)
- HPLC-MS/MS: an ultimate method for toxicant identification
b. Quantitative analysis of the serum level of a known toxicant in order to answer the questions:
How severe is the toxicant exposure? Is a specific treatment procedure needed?
Examples:
Acetaminophen (by FPIA) - Fluorescence polarization immunoassay to determine if the acetaminophen plasma conc is high (>150 mg/L at 4 hrs) and N-acetylcysteine administration is needed.
Li (by flame photometry) – is hemodialysis necessary?
Salicylate (by Trinder reaction:) – is hemodialysis necessary?
Methanol, ethylene glycol (by GC) – is hemodialysis necessary?
Digoxin*, theophylline*, phenytoin*, (by FPIA) – is hemoperfusion necessary?
NOTE: (FPIA is also used for monitoring drug levels in plasma, e.g., gentamicin.)
2
IMPORTANT NOTE:
The Posm and osmolal gap are used as a rapid screening tests for methanol and ethylene glycol intoxication. A high plasma osmolal gap is highly suggestive of the presence of either methanol or ethylene glycol (and their acidic metabolites).(Differential dg.: A high plasma osmolal gap is also seen in diabetic or alcoholic keto-acidosis, lactic acidosis, and after infusion of hypertonic mannitol.)