2. • Relatively new metal in terms of humans
– Encountered in earth’s crust combined with chlorine
(CdCl2), oxygen (CdO),sulphur (CdS)
– Exists as small particles in air, result of smelting, soldering or
other high temprature industrial processes.
• Sources:
– natural rock weathering
– copper, lead and zinc smelting auto exhaust
– cigarette smoke (a cigarette contains 1-2 ug Cd)
• Uses:
– metal plating
– nickel-cadmium batteries
– paint pigments (blue)
– plastic stabilizers
– photographic chemicals
– fungicides
• readily absorbed and accumulated in plants and Food are most
common routes of exposure for general population

3. Pharmacokinetics
• inhalation:
–smelters, cigarette smoke
–18-50% absorbed
• ingestion:
• main source is liver and kidney of meats
• 6% absorbed
• greater if deficient in calcium, zinc or
iron

4. • distribution:
– bound to albumin in plasma and red blood
cells
– transported to liver, pancreas, prostate and
kidney, with eventual transfer to kidney
• 50-75% of total body Cd is found in liver and
kidney
Metallothionein: protein rich in cysteine
-traps Cd especially in kidney
-synthesis induced by Cd
• Elimination:
- urine
– half-life in humans is 22 - 30 years

5. Cadmium toxicity
• Caused by excessive exposure to cadmium
• No constructive purpose in the human body.
• Extremely toxic even in low
concentrations, and will accumulat in
organisms and ecosystems

7. pathophysiology
–binding to –SH groups
–competing with Zn and Se for inclusion into
metalloenzymes
–competing with calcium for binding sites
(calmodulin)
• Kidney toxicity:
–free Cd binds to kidney glomerulus
–proximal tubule dysfunction

8. • Lung toxicity:
– edema and emphysema by killing lung
macrophages
• Skeletal effects:
– Osteoporosis and osteomalacia (pseudofractures)
• Cancer:
– carcinogenic in animal studies
– ~8% of lung cancers may be attributable to Cd

9. Two mechanisms are involved in cadmium
mutagenicity,
 Induction of reactive oxygen species and
 Inhibition of DNA repair
 Cystein is a precursor to the anti-oxidant protein
glutathione and is also required for metallothionein
which is a protein that binds to cadmium specifically
 Intracellular, cadmium binds to metallothionein
 Cadmium is released into the plasma after haemolysis
or when the erythrocytes lifetime has expired
 Cadmium is transported in blood plasma initially bound
to albumin
 Cadmium bound to albumin is preferentially taken up
by the liver

10. In the liver, cadmium induces the synthesis of
metallothionein
After a few days exposure metallothionein-
bound cadmium appears in the blood plasma.
Plasma metallothionein play an important role
in transport of cadmium

11. Mechanism responsible for the selective accumulation of cadmium in proximal tubular cells
Mechanism

13. EFFECTS OF POISONING:

14. Signs and symptoms of toxicity
Eating food or drinking water contaminated with high levels of
cadmium can result in:
• Vomiting / nausea
• Stomach cramps
• diarrhea
• Kidney damage
• Fragile bones
• Death
Breathing in cadmium can result in:
• Lung damage (chest pain or shortness of breath)
• Kidney disease
• Fragile bones
• Death

15. Cadmium detection and treatment
• What would cause you to suspect Cd toxicity?
- mainly the history
• What tests could you do to detect exposure or effects?
– detected via increased excretion of proteins, amino acids
and calcium by the kidney (proteinurea)
– Urine and blood cadmium levels can be detected
– Level of cadmium in liver also may be obtained
• What could you prescribe for treatment?
– Acute inhalation: fluid replacement, mechanical ventilation
– Acute ingestion: emesis and gastric lavage
– Chronic:
• chelation therapy is ineffective so only treatment is to
remove source

16.  Elements like calcium and selenium are shown to
have protective effect against cadmium-induced
toxicity
 Adequate levels of zinc in the body helps to
displace cadmium from the tissues
 Potent antioxidants like Vitamin C, E,
glutathione, methionine, glycine, cysteine has
great protective efficiency.
TREATMENT

17. Cadmium (Cd)
Epidemics/case studiesJapan (1940s)
• effluent (outflow) from a lead-
processing plant washed over adjacent
rice paddies for many years
– rice accumulated high level of Cd
– community was poor (and therefore
malnourished with respect to
calcium)
– acute toxicity: renal
failure, anemia, severe muscle pain
• named "Itai-Itai" disease
("ouch, ouch")
Itai-itai victim

19. prevention
• Do not smoke. Smoking is the single most important source
of cadmium intake for most persons.
• If you maintain a vegetable garden, consider having
fertilizers tested for cadmium. Some fertilizers have been
found to be high in cadmium, which may then concentrate
in your vegetables. Avoid any use of cadmium containing
fungicides near your vegetable gardens.
• Eat a balanced diet that provides enough
calcium, iron, protein, and zinc.
• Take inventory of and properly store (out of the reach of
children) cadmium-containing products in your home
(eg, fungicides, batteries, metals, fabric dyes, ceramic/glass
glazes, fertilizer); check the label for cadmium or call the
manufacturer to find out if the product contains cadmium.

20. Case
• A 2 year old boy presents to the emergency
department with a chief complaint of blood-
tinged vomiting. His mother was tending to her
newborn infant when the patient climbed up and
grabbed his mom's bottle of iron pills from the
counter. He was able to open the bottle and
thinking that the pills looked like candy, he ate
them. His mother brought in her bottle of ferrous
sulfate 325 mg (65 mg elemental iron) tablets.
Counting the iron tablets in the bottle there is a
maximum of 15 tablets missing (975 elemental
Fe/11kg= 81 mg/kg of elemental iron ingested).

21. • Exam: VS T 36.9, P 120, R 30, BP 88/60, weight 12kg
(10th percentile). He is alert, and being carried by
mom. His skin is pink and warm with good perfusion
and capillary refill. HEENT exam is negative. His oral
mucosa is moist and there are no lesions. His neck is
nontender. Heart regular rhythm and normal rate.
Lungs are clear with good aeration. His abdomen is soft
and slightly tender in the upper quadrants, with active
bowel sound and no guarding. His distal pulses are
strong and his distal extremities are warm. He is
responding appropriately to mom.
• An abdominal series reveals radiopaque tablets in the
stomach and intestine.

22. iron toxicity
• Iron overdose has been one of the leading causes
of death caused by toxicological agents in
children younger than 6 years.
• Iron is used as a pediatric or prenatal vitamin
supplement and for treatment of anemia. Iron is
particularly tempting to young children because it
appears similar to candy.
• Patients with anemia that require frequent blood
transfusions also are at risk for developing
chronic iron toxicity.
• This condition develops in patients with sickle cell
disease, thalassemia, and myelodysplastic
syndromes.

23. • Iron is a serious and potentially fatal ingestion. It used
to be one of the leading causes of fatal poisonings in
the pediatric age group.
• Toxicity is based on the amount of elemental iron
ingested.
• The most common forms of iron include: ferrous
sulfate (20% elemental iron), ferrous fumarate (33%
elemental iron), and ferrous gluconate (11%)
• Children's multivitamin with iron preparations contain
8 to 18 mg of elemental iron per chewable tablet. A
common iron containing medication is a prenatal
vitamin, which has 325 mg ferrous sulfate (65 mg
elemental iron) per tablet.

24. PATHOPHYSIOLOGY
• Iron toxicity can be classified as corrosive or cellular toxicant:
• Corrosive toxicity: Iron is an extremely corrosive substance to the
GIT. It acts on the mucosal tissues and manifests as
nausea, hematemesis and diarrhea; patients may become
hypovolemic because of fluid and blood loss which may aggravate
the hypoperfusion, exacerbating lactic acidosis.
• Cellular toxicity: The absorption of excessive quantities of ingested
iron results in systemic iron toxicity. Excessive cellular uptake leads
to the generation of free radicals and hydrogen ions through
Fenton’s reaction. Excessive free radicals production impairs
oxidative phosphorylation causing anaerobic metabolism and lactic
acid production. The liver is one of the organs most affected by iron
toxicity, but other organs such as the heart, kidneys, lungs, and the
hematologic systems also may be impaired.

25. • There are other unknown mechanisms for cellular
injury.
• Lactic acidosis results from tissue
hypoperfusion/cellular hypoxia.
• Free iron may also cause direct damage to the
heart leading to decreased myocardial
contractility (negative inotropic effect on the
myocardium).
• Coagulopathies may occur from effects of iron on
clotting factors

26. • Fenton’s reaction:
• (1) Fe2+ + H2O2 → Fe3+ + OH· (hydroxyl radical) + OH−
• (2) Fe3+ + H2O2 → Fe2+ + OOH· (peroxide radical) + H+
• Iron is absorbed in the intestine. The peak serum level
ranges from 2 to 6 hours after ingestion of iron. Iron is
absorbed in the ferrous (Fe++) form and is oxidized to the
ferric from (Fe+++) within the cells. It is transported in the
blood bound to transferrin. The iron binding capacity
(transferrin level) is usually 300-500 mcg/dl (TIBC) and
normal serum iron levels are 50-150 mcg/dl

27. • Both corrosive and cellular toxicities of excessive
iron ingestion lead to metabolic acidosis
•
• Individuals demonstrate signs of GI toxicity with
ingestions of more than 22 mg/kg, but less than
or equal to 40 mg/kg. Moderate-to-severe
intoxication occurs when ingestion of elemental
iron exceeds 40 mg/kg. Ingestions exceeding 60
mg/kg may be lethal.

28. • With a serum iron level of less than 300 mcg/dl, the
patient is usually asymptomatic. There is potentially
moderate toxicity with an iron level between 300 to
500 mcg/dl. Serum iron levels greater than 500 mcg/dl
fall in the severe toxicity range. If the iron tablet is
enteric-coated or a sustained-released tablet, the
absorption may be delayed and a second level drawn
6-8 hours after ingestion should be considered. The
serum iron level may not be reliable if deferoxamine
has been given. Other laboratory tests that are
recommended are serum electrolytes, BUN, and
creatinine. A baseline CBC can be drawn. An abdominal
radiograph to look for radiopaque iron pills may be
helpful. There are several tests previously used in iron
poisoning which are no longer recommended

29. SIGNS AND SYMPTOMS
• Iron poisoning is often classified into 4 distinct
stages. Understanding the course of poisoning is
important, especially the second (recovery)
stage, which may lure the physician into a false
sense of security and result in premature and
inappropriate discharge of a patient.
• Stage 1[the gastrointestinal (GI) phase]:
– Nausea and diarrhea, often accompanied by
abdominal pain
– When the intoxication is severe, a hemorrhagic
component is observed in conjunction with
gastroenteritis.
– The combination of fluid and blood loss, with
additional third-spacing, may result in hypovolemia or
shock. [fatal in significant% of cases].

30. • Stage 2 [recovery phase]:
– This stage is characterized by resolution of GI
symptoms.
– This deceptive phase usually occurs 6-11 hours
postingestion and may last as long as 26 hours.
– Metabolic abnormalities during this phase may
include hypotension, metabolic acidosis, and
coagulopathy.
•
• Stage 3:
– Stage 3 is characterized by metabolic acidosis.
– Elevated liver enzymes and bilirubin are commonly
observed with coagulopathy, indicative of hepatic
dysfunction.
– Hypoglycemia may accompany liver dysfunction.

31. • Stage 4 [experienced weeks after a severe
poisoning]:
– This stage is characterized by scarring of the
healing GI tract. The stomach and/or intestines
may be affected, resulting in gastric outlet or
intestinal obstruction.

32. TREATMENTT
1. Terminate further exposure.
2- Supportive and symptomatic treatment:
-For Hypovolemia: Administer vigorous isotonic crystalloid
therapy (e.g., 0.9 isotonic sodium chloride solution, LR
solution) to attain and maintain hemodynamic stability.
3- Physical examination and history.
4- Prevent further absorption from the gut:
Because adsorption to activated charcoal is minimal, whole
bowel irrigation is the GI decontamination method of choice.
This is done using Polyethylene glycol bowel preparation
administered through NG or OG tube until rectal effluent is
clear. [Mode of action: PEG is a Laxative with strong
electrolytic and osmotic effects that has cathartic actions in
the GI tract.]

33. • Enhance elimination (move to the specific antidote)
• 6- Specific antidote [Chelating agent]:
• Chelation is the mainstay of therapy and is indicated
for:
• Serum iron levels >350 μg/dL with evidence of toxicity
• Serum iron levels >500 μg/dL regardless of signs or
symptoms.
– Deferoxamine: 8 mg of iron is bound by 100 mg of
deferoxamine. It readily chelates iron from ferritin and
hemosiderin but not transferrin. The complex is excreted
in urine and bile and gives urine a red discoloration (Vin-
rosé urine).
– Deferasirox: oral, Binds iron with high affinity in a 2:1 ratio.

34. • Deferoxamine chelates the ferric ion (Fe+++). It is
given intravenously to patients who are
symptomatic with vomiting, diarrhea, increased
anion gap metabolic acidosis, gastrointestinal
bleeding, lethargy, or hypotension. Deferoxamine
therapy is also recommended if the serum iron
level is greater than 500 mcg/dl. The iron-
deferoxamine complex (ferrioxamine) is water-
soluble and is excreted in the urine. It may cause
the urine to be pinkish-orange ("vin-rose"). The
initial dose of deferoxamine is 15 mg/kg/h. The
rate may be increased up to 25 to 40 mg/kg/h.
Rapid infusion of deferoxamine may cause
hypotension.

35. • Mortality is low in iron poisoning patients if they
do not have shock or coma. With supportive
treatment of patients with shock or coma, the
mortality rate is about 50%. If deferoxamine
treatment is added, the mortality rate drops to
10%. Patients may be discharged home from the
emergency department after 4-6 hours of
observation if they are asymptomatic, have
serum iron levels less than 300 to 500
mcg/dl, and have a negative abdominal X-ray. A
psychiatric evaluation is needed if it was an
intentional ingestion.