Clinical Chemistry 3 Toxicology Cases 9 May 2013

CASE 1

A 54 yr old male was admitted to the emergency department. The patient was conscious, but his level of consciousness (LOC) was diminished. He was neither very alert nor coherent in responding to verbal questioning. He was responsive to pain stimulus. He did not have alcohol breath or a fruity odour upon exhalation. The patient admitted that his vision was slightly blurred and that he was seeing double (diplopia). Slight nystagmus was evident. Patient experienced multiple episodes of emesis. Additional symptoms included cephalagia, slurred speech, and unsteady gait. Lips and fingernails were bluish in colour. Vital signs were as follows:

Pulse = 110 beats per minute Normal: ~ 80 Blood pressure = 100/74 mmHg Normal: 120/80 Respirations = 28 per minute Normal: 12 16

Results of initial laboratory tests were as follows: SERUM

TEST RESULT REFERENCE RANGE

Na+ 135 mmol/L [135 -145] K+ 4.5 mmol/L [3.5 5.5] Chloride 108 mmol/L [98 108] CO2, total 7.0 mmol/L [23 33] Urea 6.1 mmol/L [3.0 8.0] Creatinine 133 umol/L [60 120] Glucose random 9.0 mmol/L [

1. What course of action should the doctor pursue? 2. What is the possible origin of the calcium oxalate crystals? 3. What additional laboratory tests should be considered? 4. Calculate the osmolal gap and comment on the result. 5. Why did the urine emit a yellow-green colour when irradiated with ultraviolet light using a

Woods lamp? 6. Is the ethylene glycol concentration representative of a toxic dose? 7. Why is ethylene glycol toxic to the human body? 8. What is the treatment for ethylene glycol ingestion?

CASE 2 A 20-year-old male student was brought into hospital in a confused state, having been found at home by his flatmate with an empty bottle of salicylate tablets on his desk. On admission he was hyperventilating and sweating profusely. He was not grossly dehydrated but the inside of his mouth was dry and there was a smell of ketones on his breath. There was no history of diabetes mellitus. His pulse was 112/min, blood pressure 110/60 and temperature 39.5 C. His salicylate level was 75 ug/100mL.

2.1 Provide a possible explanation for the ketone smell on the patients breath. (2)

2.2 Describe the sequence of events resulting from high - dose salicylate ingestion (12)

2.3 When should another blood specimen be collected in this patient and why? (2)

2.4 Provide an explanation for the increased in temperature in this patient. (2)

CASE 3 A 29-year old female, arrives at the Casualty Unit of Groote Schuur Hospital by ambulance. She's pale and complains of intermittent episodes of nausea after an intentional overdose of acetaminophen at home. Awake and oriented to person, place and time, she says that she was depressed about her recent job loss and took thirty 500-mg acetaminophen tablets about 3 hours ago.

She vomited twice at home and saw a few pill fragments in the emesis. She called the ambulance after she started to vomit. She says she hasn't taken any other medication or substances, except for her daily 10 mg of loratadine for seasonal allergic rhinitis. She has no known drug or food allergies and her physical examination is unremarkable.

3.1 Discuss the effect of a toxic dose of acetaminophen on the body. (8) 3.2 When should blood samples for acetaminophen analysis be obtained? Why? (3) 3.2 Which antidotes can be used in the treatment of acetaminophen toxicity? (2) 3.3 List methods that may be used for the estimation of acetaminophen in blood. (2)

CASE 4

A 29-year-old exterminator was spraying with diazinon on the morning before he was

admitted to Karl Bremer Hospital. Shortly thereafter he noticed the onset of mild

wheezing, cough, and increased sputum production. He also began to feel

light-headed and nauseated. About one-hour later he developed vomiting, diarrhoea,

and crampy abdominal pain.

4.1 Name one cholinergic agent and state its function. (3) 4.2 How would agents e.g. diazinon affect the function of the cholinergic agent stated

in 4.1? (3) 4.3 What would be the result of the effect of agents like diazinon on the human body? (5) 4.4 Which assay would you recommend for the patient in this case? (1) 4.5 Comment on the result that you would expect for the test stated in 4.2 (2)

ANSWERS TO CASES

CASE 1

1. What course of action should the doctor pursue? The doctor suspects the patient may have ingested an abused drug or volatiles other than ethanol based on the initial group of laboratory tests. The clinician tested the patients urine for the presence of ethylene glycol by subjecting the specimen to ultraviolet light using a Wood's lamp

2. What is the possible origin of the calcium oxalate crystals. The urine oxalate crystals originate from the metabolic product oxalic acid. The identification of these crystals supports the diagnosis of ethylene glycol poisoning but does not confirm ethylene glycol exposure because there are several other reasons for finding oxalate crystals in the urine.

3. What additional laboratory tests should be considered? The clinical laboratory does not offer additional volatile substance testing and must send out specimens to a reference laboratory. Therefore, the clinician orders volatile testing (reference laboratory]; the following tests will be done in the hospital laboratory:

Measured serum osmolality by freezing-point depression osmometry

Drug of abuse urine [DAU] screen The ED physician exposed a urine specimen provided by the patient to a Wood's lamp, and the specimen emitted a yellow-green colour (i.e., it glowed). The physician suspected the presence of a chemical substance in the urine that might be ethylene glycol.

Additional laboratory tests were requested and included the following:

SERUM

TEST RESULT REFERENCE RANGE

Serum osmolality 135 ugl/L [135 -145] cTnI 0.05 ugl/L [

4. Calculate the osmolal gap and comment on the result.

Osmolal Gap = Measured Osmolality Calculated Osmolality Calculated Osmolality (mOsm/kg) = 2xNa+ + Glucose + Urea

= 2 x 135 mmol/L + 9 mmol/L + 6.1 mmol/L

= 270 + 9 + 6.1 = 285 mOsm/kg

Osmolal Gap = Measured Osmolality Calculated Osmolality Osmolal Gap = 372 285

= 87 mOsm/kg [Ref. range 5 10 mOsm/kg]

The Osmolal Gap will be increased in the presence of volatiles (e.g., methanol, ethylene glycol, ethanol, and isopropanol) using freezingpoint depression osmometer, not a vapour pressure osmometer

5. Why did the urine emit a yellow-green colour when irradiated with ultraviolet light using a Woods lamp?

Many manufacturers of radiator fluid add fluorescein, a fluorescent dye, that will produce yellow-green colour when subjected to ultraviolet light [eg, from a Wood's lamp.)

6. Is the ethylene glycol concentration representative of a toxic dose? Yes. Toxic concentrations of ethylene glycol are defined as >20.0 mg/dl., and "potentially fatal" concentrations are defined as >50.0 mg/dL.

7. Why is ethylene glycol toxic to the human body? Ethylene glycol itself is relatively nontoxic but is metabolized into toxic metabolites (e.g., oxalic acid.) 8. What is the treatment for ethylene glycol ingestion? Depending on the patient's condition, treatments may include but are not limited to haemodialysis or the administration of ethanol or fomepizole.

CASE 2

2.1 Provide a possible explanation for the ketone smell on the patients breath. (2)

At high levels of exposure salicylates stimulates fatty acid breakdown, leading to the production of ketones.

2.2 Describe the sequence of events resulting from high - dose salicylate ingestion (12)

See Notes

2.3 When should another blood specimen be collected in this patient and why? (2)

Blood should be drawn 6 hr after ingestion i.e. Absorption & distribution will then be complete.

2.4 Provide an explanation for the increased in temperature in this patient. (2)

See Notes

CASE 3 3.1 Discuss the effect of a toxic dose of acetaminophen on the body. (8) See Notes 3.2 When should blood samples for acetaminophen analysis be obtained? Why? (3) See Notes 3.2 Which antidotes can be used in the treatment of acetaminophen toxicity? (2) See Notes 3.3 List two methods that may be used for the estimation of acetaminophen in blood. (2) See Notes

CASE 4 4.1 Name one cholinergic agent and state its function. (3) Acetylcholinesterase

4.2 How would agents e.g. diazinon affect the function of the cholinergic agent in 4.1? (3) Diazinon cause acetylcholine to accumulate in the vicinity of cholinergic nerve terminals and thus are capable of producing effects equivalent to excessive stimulation of cholinergic receptors throughout the central and peripheral nervous systems.

4.3 What would be the result of the effect of agents like diazinon on the human body? (5) o Diazinon increase acetylcholine stimulation of smooth-muscle receptors

and the following can be seen:

=> heart & exocrine glands (tight chest, wheezing, sweating) => GI disruptions (vomiting, cramps, diarrhoea) => skeletal muscles (weakness, involuntary twitching, cramps) => CNS effects (tension, anxiety, insomnia, confusion)

o Death usually occurs as result of respiratory failure.

4.4 Which assay would you recommend for the patient in this case? (1) Serum butyrylcholinesterase.

4.5 Comment on the result that you would expect for the test stated in 4.2 (2) I would expect the serum butyrylcholinesterase results to be reduced.