Heavy metal disease and solvent

abuse

Unit 19.
Arsenic poisoning:
Diarrhoea Specimens:
Polyneuropathy Hair and
Pain Nails.
Vomiting
Shock Sources:
Coma Insecticides pesticides
Renal failure herbicides, shellfish,
murder.
Aluminum poisoning:

Encephalopathy Specimens:
Osteodystrophy Plasma
Alzheimer’s
disease – some Sources:
evidence for this. Contamination.
Dialysis
Cadmium poisoning

Renal tubular Specimens:

failure Blood
Urine.
Liver disease
Bone disease Sources:
Food cans
Batteries
Tires.
Lead poisoning

Acute: colic, Specimens:

Blood
seizures, coma.
Urine
Chronic: Blood smear.
anaemia, Sources:
encephalopathy, Paint, gasoline,
batteries, ceramics,
infertility, glass, pipes, solder,
abdominal pain. cosmetics.
Basophilic stippling:
Mercury poisoning
Specimens:
Nausea Urine
Vomiting Erythrocytes.
Sources:
Nephrotoxicity Vapour from spills,
thermometers etc.
Neurological Sea/lake food
Dental amalgam, say some
Paper industry waste.
Mercury vapour
Inhaling mercury vapour once used as a
cure for syphilis.
Shakespeare’s writing, baldness and social
withdrawal might have been result of Hg.
Mozart’s appearance in portrait just before
death could have been results of Hg therapy
Source: Globe and Mail 2005 01 13.
Laboratory issues:
Best methods in general use is Tandem
mass spectrometer – expensive and need
special skills to operate.
Poor precision and dubious accuracy is
common.
“Healthy” reference ranges are not known.
 30 year-old man, foundry worker,
complains of tiredness
microcytosis, anisocytosis, poikilocytosis,
anaemia – Haemoglobin 102 g/L (130-170)
Mean corpuscular volume 0.36 (0.41-0.53)
Iron 38 umol/L (10-30)
TIBC 60 umol/L (40-70)
What is his disease?
What else should be done?
What sample should be used?
Herbicides:
Products used in gardening and agriculture
can be poisonous.
The manufacturer usually has a laboratory
which will measure the herbicide and
metabolic products for no charge.
Public health authorities are interested:
Paraquat poisoning.
Dioxin
Crop duster pilot spraying
Paraquat. Inhaled some.
Respiratory failure.
Lung transplant being considered to be
carried out at TGH. Lung to be supplied by
Sunnybrook.

Paraquat measured at Chevron

Laboratories.
53 year old man in Montreal
restaurant. Grand mal seizures:
Nausea, vomiting, diffuse abdominal pain.
Blood gas pH 6.54 (7.35-7.45)
pCO2 12 mm Hg (35-45)
pO2 121 mm Hg (80-100)
Bicarbonate 2 mmol/L (21-28)
Plasma anion gap 44 mmol/L
2 hours serum CK, LD, AST, myoglobin
increased. Albumin in urine.
Montreal malmuncher (2):
Acute renal failure,
Anaemia
13th day acute pancreatitis.
Self poisoning:
Herbal and traditional remedies:
Vedic - Guggul
Chinese remedy for arthritis.
Self medications:

Some traditional remedies

contain heavy metals.
Some modern versions of
traditional remedies have drugs
added.
 55 year old Indo-Canadian, 3
months of anorexia and nausea,
abdominal pain, hypertension and arthritis.
Blood haemoglobin 74 g/L (135-170)
Mean corpuscular volume 62 fl (80-100)
Reticulocytes 9.5% (0.2-2.0)
ALT 160 U/L (5-40)
GGT 205 U/L (10-48)
Indo-Canadian (2)

Bilirubin 20 umol/L (<17)

Taking “Guggul” for arthritis.

What further tests?

Source: Arun Garg CMAJ
 58 year old Chinese-Canadian
suffers from arthritis.
He is becoming more emotionally labile and
weak. He has fat body and thin limbs.
Glucose in urine.

Laboratory work up showed steroids when

he was on the traditional medicine, less to
none when he did not take this.
 Solvents
Use liver and kidney functions tests.

Examples:
Carbon tetrachloride in varnish stripping.
Dry cleaning solvents.
Children glue sniffing.
Dioxin
Family of chemical compounds with a basic
structure of two oxygen atoms joining a pair
of benzene rings.
2,3,7,8-tetrachloridibenzo-p-dioxin usually
abbreviated to TCDD is the most common
version.
By product in the manufacturing of Agent
Orange and other herbicides.
Dioxin’s effects on man
Chloracne.
Hyperpigmentation.
Hyperkeratosis.
Sebaceous cysts.
Other: eye infections, disrupted thyroid
hormones, lowered sperm count, heart
disease, liver and nerve damage, cancer.
Dioxin
1949 250 workers exposed at Monsanto.
122 cases of chloracne. No excess deaths
after 30 years.
1963 106 workers at Philips in Amsterdam.
44 cases of chloracne. No deaths.
1976 156 workers at ICMESA plant in
Seveso, Italy. 134 cases of chloracne. No
excess mortality.
Dioxin
Press has called this the most toxic
synthetic chemical known to man.
Lethal dose to kill half (LD 50) for a male
guinea pig is 0.6 microg/kg.
LD 50 for a rat is 22 microg/kg.
But LD 50 for a hamster is 3,000
microg/kg.
LD 50 for a human is what?
Dioxin, conclusion:
Nasty substance.
Not a good murder weapon.
May cause increased cancer in humans but
this is not proven.
Hype and public fear drive the hysteria
regarding this substance. Viktor Yushenko,
Ukrainian position leader then president
2004.
Toxicology screen using urine:
Usually picks up cocaine, marijuana
amphetamines, tricyclic antidepressants.
Can use thin layer chromatography.
Separate technique for the alcohols. Dip
stick or TLC or gas chromatography
Bebe Driver in MVA
Osmolality of 330 mosm/kg (280-300)
indicated another anion present more than
just ethanol.
This could contributed up to 20 mmol/L to
the osmolality
Urine drug screen needed for forensic needs
or just to know how to get her down.
Hair analysis:
Refer to earlier section.
Pre analytical factors
Analytical factors
Post analytical factors
Therapeutic drug monitoring

Unit 20.
 Therapeutic drug monitoring
Used to check that dose is right.
Issues with absorption, metabolism, excretion.
Need to get to the “steady state”.
Used when there is no objective measure of
effectiveness.
Must be a relationship between plasma drug
and clinical effect.
Present use of therapeutic drug
monitoring:
Carbamazepine Seizures
Cyclosporin Transplant
immunosuppression
Congestive heart
Digoxin failure, arrhythmias.

Gentamicin Antibiotic
Lithium Bipolar disease
Methotrexate Cancer, abortions.
Present TDM (2):
Phenytoin Seizures
Phenobarbitone Seizures
Valproate Seizures.

Theophylline Bronchodilator
Caffeine Bronchodilator
Sub therapeutic levels:
Not enough given
Patient does not take it
Malabsorption
Metabolism/excretion is exceptionally
rapid.
Toxic levels:
Too much given
Patient overdosing
Renal function is impaired
Hepatic metabolism is impaired.
Current problems:
Modern medicine is suffering from drug
addiction.
Benefit of many drugs has not been
established.
Drugs interact. (David Bailey – Canada’s
first sub 4 minute mile is expert, Western)
Sunnybrook – elderly come in on 8 drugs
and leave with two.
6 year-old boy on carbamazepine
blood 5.5 mg/L,
saliva 1.8 mg/L initially
One year later test saliva gave15 mg/L
Orange juice 1 hour before sample.
Blood 6.2 mg/L
Pre analytical problem.
18 year-old chronic asthmatic
900 mg theophylline/day, to give serum 18
mg/L
Acute asthma attack.
0.9 mg/kg/hr IV to 1300 mg/day for 72
hours. No measurement of theophylline.
Patient became brain damaged.
Functions gradually returned except for
sight.
Renal diseases

Unit 21.
disease: nitrogenous waste
effects
Nausea, vomiting, Smell,
dyspepsia. Sallow skin
Pruritus. Scratch marks
Anorexia Pericardial or pleural
Lethargy rub
Chest pain, Cognitive impairment,
Mental dullness twitching,
Parathesia. Neuropathy.
Symptoms and signs: protein
loss, electrolyte loss

Thirst Oedema.
Polyuria, Signs of heart
nocturia, oliguria, failure.
anuria. Hypertension or
Weakness. hypotension.
Breathlessness.
Symptoms and signs of renal
disease: acidosis

Breathlessness Kussmaul
respiration.
Cognitive
impairment.
Symptoms and signs of renal
disease: endocrine
Anaemia (EPO Pallor.
lack)
 Lethargy
 Dyspnoea

Impaired vitamin Signs of

D osteomalacia or
 Bone pain.
rickets.
Symptoms and signs of diseases
with renal failure as a feature:
Urinary tract Loin tenderness.
infections Palpable kidneys or
 Haematuria bladder.
 Loin pain
 Dysuria
Vasculitic skin rash
Systemic disease such
as lupus
in collagen
diseases.
And so on.
And so on.
Testing for renal diseases:
Glomerular filtration rate:
plasma creatinine,
Creatinine clearance,
plasma urea.
[plasma Cystatin C]
Tubular functions:
plasma and urine sodium
plasma and/or urine Osmolality.
Urinalysis, the famous five:
pH – acidification function.
Protein – glomerular membrane problem or
inflammatory disease of tubules.
Glucose – overload or lower renal threshold
Blood – bleeding into the genital urinary
tract.
Specific gravity – concentrating function.
 Renal disease is acute or chronic
Renal disease may be
Pre renal
Renal
 Glomerular membrane
 Tubule

Post renal.
Pre renal failure:
Low glomerular filtration rate,
Lack of blood volume/ renal shut down to
maintain blood pressure as in
Dehydration
Shock
Blood loss
Compare serum to urine Na and / or
osmolality
Pre renal case:
20 year old man fell into pet food meat
grinder. Legs are crushed.
Rushed to the emergency department.
Now making little or no urine.

In the last few years there have been two

cases like this from North York.
Young man with severe crushing
injuries, oliguria:
Serum sodium 135 mmol/L(135-147)
Urine sodium 55 mmol/L(50-150)
Serum potassium 6.3 mmol/L(3.5-5)
Serum chloride 96 mmol/L (96-108)
Serum bicarbonate 15 mmol/L(22-30)
Serum creatinine 790 umol/L(50-120)
Urine creatinine 5.3 mmol/L(7-16)
Serum urea 55 mmol/L (3-7)
 Young man with severe crushing
injuries (2):
Serum osmolality 335 mmol/kg (290-300)
Urine osmolality 360 mmol/kg (50-1,250)

What is the evidence for renal failure?

Compare serum to urine for Na, creatinine
and osmolality.
Why is serum K so high? Tissue damage
Renal failure:
Acute glomerular damage
Acute tubular necrosis
Chronic diffuse bilateral kidney disease or
damage.
GFR: Plasma creatinine, urea, creatinine
clearance adjusted for age, sex, race.
Tubular problems: s- and u-Na /osmolality.
Acute renal failure:
Oliguria, diuretic and recovery.

Causes:
pre renal causes 60%
Urinary obstruction 10%
Glomerulonephritis 10%
Drugs and interstitial nephritis 10%
Acute tubular necrosis, tests:

Plasma creatinine
Plasma and urine sodium.
Plasma potassium.
Urine protein.
Urinalysis for casts.
40 year old woman, manic
depressive, on lithium therapy
Sent home for Christmas, now returned to
metabolic unit in tired and confused state.
Serum sodium 180 mmol/L (137-145)
Serum potassium 3.5 mmol/L (3.5-5.0)
Serum chloride 135 mmol/L (96-108)
Serum bicarbonate 20 mmol/L (22-30)
Serum urea 20 mmol/L (3-7)
Serum creatinine 140 umol/L (50-120)
Chronic renal failure:
Progressive renal damage.
Can be slowed by decreasing protein intake
and
Lowering blood pressure
Goes on to end stage renal disease
Then dialysis or renal transplant.
Death.
Chronic renal failure symptoms:
Tired Mental confusion
Skin colour gray, Feet burn
yellow Muscles twitch
Oedema Libido decreased
Short of breath Skin itches
Irritable Atherosclerosis
Insomnia Osteodystrophy
Gastric Anaemia.
Chronic renal failure, laboratory
Urine protein
Plasma creatinine
Plasma calcium
Plasma phosphate
Plasma urate.
Blood gases (acidosis), sodium, urinalysis,
Immunological test in diagnosis.
 70 year-old woman took aspirin
regularly. Now is dopey.
Serum sodium 133 mmol/L (135-147)
Urine sodium 29 mmol/L (50-150)
Serum potassium 5.1 mmol/L (3.5-5)
Serum chloride 101 mmol/L (96-108)
Serum bicarbonate 16 mmol/L (22-30)
Serum creatinine 1,130 umol/L (50-120)
Urine creatinine 7 mmol/L (7-16)
 Old woman Aspirin user (2):
Serum osmolality 315 mmol/kg (290-300)
Urine osmolality 330 mmol/kg (50- 1,250)
Serum calcium 1.7 mmol/L (2.2-2.6)
Serum phosphate 2.8 mmol/L (0.8-1.5)

What is the evidence for renal disease?

Creatinine, urea, calcium and phosphate.
End stage renal (kidney) failure:

Peritoneal dialysis
Haemodialysis.
Transplant.
Death.
Early renal failure -proteinuria

A useful marker for early renal failure.

About 30 mg/L excreted usually.
Overflow or
Glomerular or
Tubular or
Secretory.
 The most proteinuria: Nephrotic
syndrome:
Protein loss 5-10 g/d.
High molecular weight proteins are spared
so lipoproteins, serum cholesterol increased.
Causes:
Glomerulonephritis, 2-7 cases/100,000
children/year.
Lupus erythematosus.
Diabetic nephropathy.
 Young girl had sore throat and
fever.
A week later: polyuria ,frothy urine.
Serum sodium 130 mmol/L (135-147)
Serum potassium 4 mmol/L (3.5-5)
Serum chloride 95 mmol/L (96-108)
Serum bicarbonate 15 mmol/L (22-30)
Serum creatinine 50 umol/L (50-120)
Serum urea 3 mmol/L (3-7)
Serum calcium 1.5 mmol/L (2.3-2.6)
Serum albumin 15 g/L (35-50)
 Girl with nephrotic syndrome (2):
Serum protein 35 g/L (60-80)
Serum cholesterol 11 mmol/L (<5.2)
Urine protein 12 g/d (0.15)

Why is serum cholesterol increased?

Will she get tetany with low calcium?
Post renal failure:

Kidney stones – obstruction.

Prostate cancer – obstruction and
cancer. This may spread into lower
spine.
Symptoms of obstruction:
Flank pain
Colic
Nausea
Vomiting
Abdominal distension.
Burning
Dysuria, urgency, frequency.
Causes of renal stones:

Dehydration.
Mineral excess:
 Diet
 Metabolic disease
 Drugs

Infections
Common causes of renal stones:
Women – urinary tract infections – triple
ammonium phosphates in urine.
Men – calcium oxalate or phosphate
Gout – urates from rich living.
Inherited diseases may lead to stones
Cystine – a Libyan jewish family.
Laboratory work in renal stones
Stone analysis for calcium, phosphate,
oxalate, urate.
Plasma calcium, albumin, phosphate,
bicarbonate, urate and ALP.
Dipstick urinalysis – blood in urine.
24 hour urine collection for metabolic
diseases.
Renal Function Tests, microbiology, X ray.
Laboratory work in prostate
enlargement:

Serum prostate specific antigen –

for cancer.
Serum alkaline phosphatase – for
spread to bone
Serum acid phosphatase - obsolete.
X ray – for spread to bone.
60 year old man with prostate
enlargement,
chronic urinary retention, lethargic, short of
breath.
Plasma sodium 140 mmol/L (135-147)
Urine sodium 74 mmol/L (50-150 mmol/d)
Plasma potassium 5.0 mmol/L (3.5-5.0)
Plasma chloride 107 mmol/L (96-108)
Plasma bicarbonate 21 mmol/L (22-30)
60 year old man with prostate
enlargement (2):
Plasma urea 57 mmol/L (3-7)
Plasma creatinine 900 umol/L (50-120)
Urine creatinine 3.6 mmol/L (7-16)
Plasma osmolality 323 mmol/L (290-300)
Urine osmolality 305 mmol/L (50-1250)
60 year-old man with prostate
problem symptoms, continued.

What are the laboratory results which

indicate renal failure?
Creatinine, urea, osmolality.

What else should be known?

Serum prostate specific antigen for prostate
cancer.