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PRACTICAL TOXICOLOGY CASES
IRON TOXICITY
Distribution in body
Fe
formation of Hb → carry O2 (Fe2+)
65%
erythrocytes
17.5%
17.5%
stored as
• Ferritin
(soluble)
• hemosiderin
(Insoluble)
(Fe3+) (in
Macrophages)
• Cyt
oxidase
• Myoglobin
Types of ironFe2+
Stomach Intestine
Blood
blood
Fe3+
Types of
Fe2+
salts
Ferrous Elemental iron
Fe2+ gluconate 12%
Fe2+ ferrochlorinate 13%
Fe2+ Sulfate 20%
Fe2+ chloride 28%
Fe2+ fumarate 33%
Fe2+
Bind with mucoprotein
Become Fe3+ & bind with transferrin
< 20 mg/kg → mild
(asymptomatic).
20 – 60 mg/kg → moderate.
60 – 180 mg/kg → severe.
200 – 250 mg/kg → lethal.
Elemental iron & degree of intoxication
E.g: patient (55 kg) ingested 60 tablets of FeSO4
325mg each.60 tab x 325 mg = 19500 mg.
20% …..i.e 100 mg FeSO4 → 20 mg elemental Fe.
19500 mg → X so X = 3900 mg.
3900 mg → 55 kg.
X ← 1kg so X = 70 mg/kg so severe.
Patients who remains asymptomatic 6 or more hrs after
ingestion are unlikely to develop symptoms later.
Iron poisoning can be divided into 4 stages.
Clinical manifestations
Stage I: 1 -6 hrs.
Stage II: 6 – 14 hrs.
Stage III: 14 – 48 hrs.
Stage IV: 4 – 6 weeks.
Diarrhoea Vomiting
Fe
Bloody diarrhoea(Melena)
Bloody vomitus(Hematemesis)
Irritation
Corrosion
Irritation Corrosion
Stage I: 1 -6 hrs
GIT
Nausea &
Vomiting
DiarrhoeaBleeddin
g
Fluid Loss
Blood Loss
Hypovolemia
Hypotension
VD of arteriol
es
Stage I: 1 -6 hrs
CVS↑ capillary permeabili
ty
Reflex tachycardia
GIT
Ferritin
Released from
damaged GIT tissue
↓ B.P hypoperfusion hypoxemia anaerobic lactic à.
Fe →uncoupling oxidation phosphorylation →↓ ATP production.
Stage I: 1 -6 hrs (cont.)CNS Lethargy, severe coma or seizures.
Lactic acidosis
Glucose not consumed Hyperglycemia (at early stage).
RS↑Medullary respiratory
center
Acidosis H+ + HCO3- H2CO3 H2O + CO2 BBB
↑R.R Tachypnea
Stage of recovery (Signs & symptoms of GIT subsides,
patient feel normal).
If patients treated early in right way cure at this stage
Stage II: 6 – 14 hrs
Fe Fe Fe
Fe Fe Fe Fe
Fe Fe
Transferrin
Fe Fe Fe
Fe
FerritinHepatic
Necrosis
↓ Prothrombin
↓ Glycogenolysis
& gluconeogenes
is
↓ NH3 detoxification
Hypoglycemia
Hepatic encephalopathy (Hepatic
coma)
Fe in GIT(erosion)
carrier (part of iron) + Free ironblood
Fe Fe Fe
Fe
deposition in soft tissue.
↑ Prothrombin time
Stage III: 14 – 48 hrs (hepatic stage)
Hypoperfusio
n Hypoxia
Uncoupling oxidative phosphorylation
Excretion of
HCO3-
Metabolic
AcidosisFe
↓
Lipolysis (due to
Hypoglycemia)
FFA Ketones
bodies
Stage III: 14 – 48 hrs (cont.)
Invasion of damaged intestinal
mucosa by bacteria
Leukocytosis
Passed into blood
Sepsis
Fever
Uncoupling oxidative
phosphorylation
Shock
Hypotension
Stage III: 14 – 48 hrs (cont.)
Hepatic cirrhosis.
Pyloric stricture (pyloric stenosis) → corrosive
action.
Stage IV: 4 – 6 weeks
Laboratory Diagnosis
1. Serum iron concentration: (70 – 170 mg/dl)
If > 170 mg/dl but < 300 mg/dl→ Mild toxicity
(rarely).
If = 300–500 mg/dl→ Moderate toxicity (potential).
If > 500 mg/dl → Severe & Lethal.
N.B: we must make X-ray in the same time to be sure that all iron is absorbed into the blood & there is no opaque body in the stomach for 48 hrs.
Laboratory Diagnosis (cont.)2. Total iron binding capacity (TIBC): measurement of
transferrin (200 – 400 μg/dl).
3. % Transferrin saturation
• = Serum Fe conc / TIBC
• Normal: 15-50% in♀, 20-50 % in ♂
• % indicates amount of free Fe in serum
4. Blood glucose > 150 mg/dl serious (early stage).
5. Leucocytes > 15000/cm³ serious.
6. PT.
7. Electrolytes (HCO3, Vomiting).
8. Blood matching test (exchange transfusion).
9. X-ray → opaque.
Therapeutic Measures
a. Emetics: as Ipeca syrup (if no hypotension or vomiting
(hematemesis)).
b. Gastric lavage: by NaHCO3 2-3%
NaHCO3 + Fe2+ → ferrous carbonate (insoluble salt, thus
prevent absorption to blood)
A) Gut decontamination:
c. Activated charcoal: Not used (has no affinity).
d. Cathartics: used if no diarrhea & some iron reach
intestine.
A) Gut decontamination (cont.):
Therapeutic Measures (cont.)
B) Antidote (Deferoxamine, Desferal)
Used when?
Serum iron > 500 mg/dl, ↑ blood glucose, ↑ WBCs, ↓ B.P,
seizures.
Bind what?
Deferoxamine + free iron (Fe3+ )→ Ferrioxamine (sol coloured).
Also bind with transferrin, ferritin, hemosiderin
Not bind with iron in Hb or in cyt P 450.
Therapeutic Measures (cont.)
B) Antidote (cont.)
• Dose:
Provocative dose: 25 – 50 mg/kg I.M if vin rose
colour of urine excessive iron in blood.
Dose: 50 mg/kg I.M every 4-6hrs.
In Severe case: 15 mg/kg/hr I.V infusion.
If ↑ rate: hypotension, erythema & urticaria.
Antidote must be tapered on 24hrs to prevent
pulmonary edema.
Endpoint of ttt is the disappearance of vin rose
colour.
Therapeutic Measures (cont.)
B) Antidote (cont.)
N.B:
• Deferoxamine is not contraindicated in pregnancy.
• Deferoxamine may be transported across the placenta, chelating
iron in utero so making iron therapy necessary at birth.
Therapeutic Measures (cont.)
Therapeutic Measures (cont.)
Hypotension:
• Patients should be placed in Trendlenburg position.
• Normal saline (I.V, 1-2 liter)- not ↑ to avoid cerebral &
pulmonary oedema)
• Dopamine (2-5 mg/kg/min).
• NE (0.1 – 0.2 mg/kg/min, if ↑ dose tissue ischemia).
Seizures: diazepam.
Exchange transfusion: may be attempted in patients who
remain oliguric.
C) Adjunctive treatment:
A 5 year old girl, weighing 25 kg, was brought 5 hours to
hospital after ingesting 25 tablets of her mother’s
ferrous chloride medicament. The girl was lethargic, with
abdominal pain, diarrhea and hemotemesis. Her vital
signs were B.P 70/50mmHg, R.R 30/min. Blood analysis
revealed elevated level of lactic acidosis, and a serum
iron level of 400µg/dl.
CASE-1
Was this a toxic dose, CALCULATE in
details.
If this was a toxic dose, what is the
degree of toxicity, WHY?
In which stage is this girl?, rationalize
your answer.
What is the cause of her low blood
pressure?
Answer the following:
A 16 year old boy, weighing 60 kg, committed suicide
by ingesting 70 tablets of ferrous sulfate. He was
brought to the E.D 6 hours after ingestion. The boy
was lethargic and complained of homotemesis and
abdominal pain. Upon examination he was found
hypotensive, with increased level of lactic acid;
testing his serum iron level it was 400µg/dl. In the
department they started giving him an antidote, and
shortly after his urine turned vin-rose.
CASE-2
Was this a toxic dose, CALCULATE in
details
If this was a toxic dose, what is the degree
of toxicity, WHY?
Explain WHY was the urine color turned
vin-rose? What does this color indicate?
What is the cause of his elevated lactic
acid level?
Answer the following:
C. B. is a 35-year-old 55 kg female who ingested sixty
325 mg tablets of ferrous sulfate six hours before
coming to the hospital. On admission, she was
diaphoretic, lethargic, and complained of abdominal
pain, nausea, and vomiting. Emesis in the emergency
department was guaiac positive. Vital signs were BP
85/60 mm Hg, pulse 135/minute, respirations
34/minute, and temperature 98.6° F.
CASE-3
Assess the potential severity of this
ingestion.
What additional laboratory information
would be useful?
A flat plate x-ray of the abdomen revealed
a clump of undissolved tablets in C. B.’s
stomach. What measures can be taken to
decrease iron absorption?
Answer the following:
C. B.’s serum iron concentration (on
admission was 680 mcg/dL (70 to 170); her
TIBC was 400 mcg of iron/dL (300 to 400).
Is chelation therapy with deferoxamine
indicated?
How should deferoxamine be
administered? What side effects are
associated with its use? What are the
endpoints of treatment?
What general treatment measures are
necessary in C. B.’s case?