6 - Iron

Question 1

What is the leading cause of fatal poisonings in children?

Answer 1

Iron toxicity

Question 2

Rate the 3 types of iron based on % of elemental iron

Answer 2

Gluconate < sulfate < fumarate

Question 3

Describe iron absorption

Answer 3

• Active process regulated by level of body iron stores and demands of erythropoiesis
• Ferrous iron absorbed into mucosal cell (duodenum and jejunum), oxidized to ferric iron

Question 4

Which form of iron is most available for absorption?

Answer 4

Heme iron (instead of inorganic forms)

Question 5

What is the daily intake of iron and how much is absorbed?

Answer 5

• Daily intake = 10-20 mg

- Amount absorbed = 1-2 mg

Question 6

Describe distribution of iron

Answer 6

• In plasma, iron is bound to transferrin (transferrin system normally 1/3 saturated, normally no free iron present in serum)
• In OD, acute corrosive effect of iron on GI tract mucosa enhances absorption (transferrin system may become saturated)
• In tissue, iron is stored as ferritin

Question 7

Describe iron elimination

Answer 7

• No physiologic mechanism for iron excretion

- Sweat, bile, desquamation of skin and mucosal surfaces

Question 8

What is a toxic dose of iron?

Answer 8

10-20 mg/kg of elemental iron

Question 9

What are the effects of iron toxicity?

Answer 9

• Direct corrosive effects on gastric and intestinal mucosa (vomiting, abdominal pain, diarrhea, ulceration, hematemesis, melena)
• • Hypovolemia = tissue hypoperfusion = metabolic acidosis
• High ferritin levels cause tissue damage and release of vasoactive substances
• Iron concentrates in mitochondria disrupting oxidative phosphorylation, free radical formation, lipid peroxidation = cell death and tissue injury

Question 10

Describe the effects of iron toxicity in the GI tract

Answer 10

• Clinically correlates to -> N/V, abdominal pain, hematemesis, diarrhea, melena
• Acute corrosive effects = perforation and peritonitis, which may enhance iron absorption

Question 11

What causes hepatic effects of iron toxicity?

Answer 11

Direct result of free iron concentrations in hepatocyte during first absorptive pass

Question 12

Acute manifestations of hepatic effects of iron toxicity

Answer 12

• Electron transport abnormalities
• Lactate production
• Glycogen depletion
• Enzymatic dysfunction (metabolic acidosis and hyperglycemia)

Question 13

Severe manifestations of hepatic effects of acute iron toxicity

Answer 13

• Hyperbilirubinemia
• Aminotransferase abnormalities
• Coagulopathy
• Diffused tissue necrosis
• Disruption of normal metabolic pathways

Question 14

CV effects of iron toxicity

Answer 14

• Free Fe -> venodilation, CV compromise, shock
• Acute volume loss from GI tract -> vomiting, diarrhea, hemorrhage
• Direct cytotoxic effects -> capillary leakage, plasma loss

Question 15

Neurological effects of iron toxicity

Answer 15

• Lethargy and weakness common in severe poisonings

- Coma

Question 16

Describe the initial period of iron toxicity (stage 1)

Answer 16

• 0.5 - 6 hours after ingestion
• Considered local toxicity
• N/V, severe gastroenteritis, abdominal pain, diarrhea, hypotension, lethargy; may proceed rapidly to stage 3

Question 17

Describe the latent period of iron toxicity (stage 2)

Answer 17

• 6 - 24 hours after ingestion

- Pt may recover or progress to stage 3 (depends on dose)

Question 18

Describe the period of systemic iron toxicity (stage 3)

Answer 18

• 4 - 40 hours after ingestion –> pallor or cyanosis, lethargy, hypotension, disorientation, coma, shock, convulsions, fever, hyperglycemia, leukocytosis, metabolic acidosis
• 2-4 days after ingestion –> jaundice, hypoglycemia, elevated transaminases, prolonged clotting times, thrombocytopenia, hemorrhage, renal failure, pulmonary edema

Question 19

Describe late complication of iron toxicity

Answer 19

• 2-8 weeks after ingestion

- GI obstruction, pyloric stenosis secondary to scarring, gastric fibrosis, strictures

Question 20

What do the different doses of iron ingestion correlate to?

Answer 20

• < 20 mg/kg = usually asymptomatic
• 20 – 30 mg/kg = may produce self-limiting vomiting and diarrhea
• > 40 mg/kg = potentially serious
• > 60 mg/kg = potentially lethal

Question 21

Diagnosis of iron toxicity

Answer 21

• Hx of exposure
• Presence of vomiting, diarrhea, hypotension
• Lab involvement (Fe serum level)
• Abdominal radiograph

Question 22

What does the Fe serum level correlate to?

Answer 22

• Normal Fe serum level = 80-180 mcg/dL
• Toxicity associated w/ values > 350 mcg/dL
• “Action” level > 500 mcg/dL

Question 23

Interventions for iron toxicity

Answer 23

• ABC, basic life support
• Gastric emptying (gastric lavage, whole-bowel irrigation) -> must be careful especially in px w/ GI tract injuries as this procedures can lead to perforation
• Chelators

Question 24

Is activated charcoal used for iron toxicity?

Answer 24

• Not effective and dangerous

- Iron not really absorbed by AC

Question 25

What is deferoxamine mesylate (DFO)? How is it administered

Answer 25

- Specific iron-binding ligand - Affinity constant for iron over other metal ions or calcium - Chelates free iron and iron of ferritin (not iron bound to hemoglobin or cytochromes) - Constant IV infusion at rate of up to 15 mg/kg/h

Question 26

AE of DFO

Answer 26

- Histamine release - DFO-iron complex - Excessive intracellular chelation (oxidant damage) - In acute use --> hypotension, infections, pulmonary toxicity - In chronic use --> auditory/ ocular and pulmonary toxicity and infections

Question 27

What is ferrioxamine? How is it administered?

Answer 27

- Iron-DFO complex that is non-toxic and excreted in urine (orange, pink or brown) - IV, IM, or SC (IV preferred, removes much more iron)

Question 28

When to discontinue DFO therapy?

Answer 28

- Pt returns to asymptomatic state after presumed latent period has passed - Serum iron < 150 ug/dL - Return to normal urine colour

Question 29

Can ferrioxamine be used in pregnant women?

Answer 29

Yes