Heavy Metals

Question 1

The main absorption route of lead in adults and children:

Answer 1

Respiratory tract 30-70% in adults (less complete in GIT 10%)
Alimentary absorption in children 50% (three times than for adults)

Question 2

Lead disposition in the body comprises three major pools:

Answer 2

Blood pool
Intermediate pool (skin and muscle)
Stable pool (dentine and skeleton)

Question 3

S&S of mild lead poisoning:

Answer 3

Lethargy
Anorexia
Abdominal discomfort
Arthralgia

Question 4

S&S of moderate lead poisoning:

Answer 4

Anemia
Headache
Abdominal cramps
Gingival lead line
Peripheral neuropathy (motor)

Question 5

S&S of severe lead poisoning:

Answer 5

Convulsion
Coma
Encephalopathy
Renal failure

Question 6

Pathophysiology of lead poisoning :

Answer 6

1. High affinity to sulfahydryl group, thus inihibits sulfahydryl dependent enzymes.
2. It competes with calcium, inhibiting its action in important areas, such as mitochondria oxidative phosphorylation.
3. It can affect the genetic transcription of DNA by interaction with nucleic acid binding proteins.

Question 7

Complications of lead poisoning :

Answer 7

Hematological: Hypochromic microcytic anemia with basophilic stippling RBCs.
Renal:
Chronic : interstitial nephritis and CRF
Acute: PT dysfunction (gycosyrua, aminoaciduria, and hyperphosphaturia).
Neurological:
Adult: range from mild lethargy to severe motor neuropathy (wrist drop)
Children: encephalopathy (acute) and impaired intelligence (chronic low-level exposure)

Question 8

How does lead toxicity cause intelligence impairment:

Answer 8

Due to the effect on cell to cell connections in the immature brain.

Question 9

How does lead toxicity cause encephalopathy :

Answer 9

1. Disruption of the BBB
2. Impairment of intracellular functions of Ca lead to loss of integrity of tight junctions bt brain epithelial cells, thus subsequent passage of plasma into the brain cuase cerebral edema.

Question 10

Diagnosis of lead toxicity:

Answer 10

Blood lead concentration (>30ųg/dl)
Zinc protoporphyrin (>50ųg/dl)
urinary lead excretion following a dose of sodium calcium adetate
Urinary ALA excretion and ALAD activity

Question 11

Treatment of lead poisoning:

Answer 11

Chelating agent:

Sodium calcium adetate 50-80mg/kg/12 for 2-5 days

Succimer (2-3 dimercaptosuccinic acid)
High affinity to lead, suitable for mouth administration, and wide therapeutic index. 10-30mg/kg/day for 5-7 days.

Question 12

Why is arsenic considered a murder weapon?

Answer 12

It resembles white sugar, tastless, and odorless

Question 13

Therapeutic uses of arsenic:

Answer 13

Arsenic trioxide:Acute promyelocytic leukemia
Arsenic sulfide: psoriasis, syphilis, asthma, rheumatism, hemorrhoids, cough, and pruritus.

Question 14

Arsenic exist in:

Answer 14

1. Arsine gas
2. Metalloid :
   Inorganic arsenite (trivalent)
   Organic arsenate (pentavalent)
   Note: III is 60 times more toxic than V

Question 15

Mode of exposure and sources of arsenic:

Answer 15

Inhalation
Ingestion
Absorption from skin
Seafood and fish (organic)
Plant or soil that irrigated with arsenic contaminates water (inorganic)

Question 16

Arsenic metabolism:

Answer 16

Hepatic biomethylation to form:
Monomethylarsonic acid and dimethylarsinic acid that are less toxic
50% excreted to urin
Small amoun ot Inorganic is excreted unchanged

Question 17

Acute arsenic poisoning, highest concentration is found in

Answer 17

Liver and kindeys

Question 18

Even when arsenic is eliminated from vital organs, a small amount remains in:

Answer 18

Keratin rich tissues: nails, hair, and skin.

Question 19

Mechanism of arsenic toxicity:

Answer 19

1. Inactivate more than 200 enzymes (enzymes with SH group).
2. substituted for phosphate in high energy compound such as ATP.
3. Massive transudation of fluid into the bowel lumen.
4. Inhibits gluconeogensis (block conversion of pyruvate to actyle coenzyme A).
5. Direct effects on blood vessels or large organs (caustic)
6. Nerve damage and cancer (long-term exposure)
7. Inhaled gas combines with Hg (severe hemolysis and anemia).

Question 20

Lethal dose of arsenic:

Answer 20

100-300 mg
0.6mg/kg/day

Question 21

S&S of acute arsenic poisoning

Answer 21

1. N&V, abdominal pain, and profuse watery or bloody diarrhea.
2. Cardiac arrest, shock, prologed QT interval, and hypotension.
3. Acute tubular necrosis
4. Central hepatic necrosis
5. Anemia due to hemolysis and GIT hemorrhage.
6. Rhabdomyolysis, acute myopathy, and fevere.

Question 22

S&S of chronic arsenic poisoning:

Answer 22

Peripheral neuropathy: sensory more than motor (painful paresthesias)
Black foot disease: acrocyanosis and raynaud’s phenomenon.
Dermatological affects: alopecia, palmoplantar keratosis, hyper or hypo-pigmentation, and Mee’s lines

Question 23

What is mee’s lines:

Answer 23

Transverse white lines in the nails appear several weeks after arsenic exposure.

Question 24

Aresnic toxicity investigation:

Answer 24

• 24h urine test: most reliable.
• Arsenic level in hair, nail, and other tissues.
• Abdominal radiograph: opaque on x-ray, and it appears as barium like opacities

Question 25

Investigation for differentiation between acute and chronic arsenic toxicity:

Answer 25

Level bt 0.1 to 0.5mg/kg on hair sample indicates chronic poisoning while 1.0 to 3.0mg/kg indicates acute poisoning.

Question 26

Treatment of arsenic toxicity:

Answer 26

chelation therapy: Chelation may be of greatest benefit to:
1. patient exposed to a high level of arsenic for a short period.
2. To patients with chronic poisoning who recently were exposed to high levels that were superimposed on their chromic toxicity.

Question 27

Arsenic chlating agents :

Answer 27

Dimercaprol
Succimer (DMSA)
Di-merval (DMPS)
D-penicillamine