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?