Lecture 6 - Iron Flashcards
Why are we only dealing with treatment of acute iron toxicity?
chronic toxicity usually doesn’t happen, we don’t absorb more than what we need unless you take a bunch at once (acute)
What is iron commonly used for?
- anemia
- prenatal supplement
- daily nutritional supplement
Absorption of iron is an active process regulated by the level of body iron stores and demands for ________
erythropoiesis (production of red blood cells)
_____ iron is absorbed into the mucosal cell (duodenum and jejunum) and is oxidized to ferric iron
ferrous
____ iron is more available for absorption than inorganic forms of iron
heme
What is the daily intake or iron?
10-20mg
How much is actually absorbed from 10-20mg?
1-2 mg
In plasma, iron is bound to ______
transferrin
Transferrin system is normally ___ saturated
1/3
T or F: normally there is free iron present in serum
False: normally there is no free iron present in serum
In overdose, the acute corrosive effect of iron on the GIT mucosa ______ absorption and the transferrin system may become saturated.
enhances
In tissue, iron is stored as ______
ferritin
Is there a physiologic mechanism for iron excretion?
No
How will the body try and excrete iron?
- sweat
- bile
- desquamation of the skin and mucosal surfaces (sort of like peeling)
What is the toxic dose of elemental iron?
10-20mg/kg of elemental iron
What are some direct corrosive effects of iron on the gastric and intestinal mucosa?
ulceration, severe edema, hemorrhage, infarction, venous thrombosis
which leads to:
vomiting, abdominal pain, diarrhea, ulceration, hematemesis, melena
hypovolemia = tissue perfusion = ______ _________
metabolic acidosis
What do high ferritin levels do?
cause tissue damage and release of vasoactive substances
Iron concentrates in the _______ which disrupts oxidative phosphorylation, free radical formation and lipid peroxidation which leads to cell death and tissue injury
mitochondria
What are acute corrosive effects of iron toxicity?
perforation and peritonitis - which may enhance iron absorption
How does iron cause hepatic toxicity?
Free iron concentrations in the hepatocyte during first absorptive pass will cause:
- electron transport abnormalities
- lactate production
- glycogen depletion
- enzymatic dysfunction
What type of acid base disorder comes from iron toxicity?
metabolic acidosis
How does iron toxicity affect blood sugar?
hyperglycemia
With acute iron poisoning, hepatocellular toxicity may be severe. What will this cause?
- hyperbilirubinemia
- aminotransferase abnormalities
- coagulopathy
- diffused tissue necrosis
- disruption of normal metabolic pathways
How will free iron affect CV toxicity?
- venodilation
- CV compromise
- shock
What does acute volume loss from GIT cause?
- vomiting
- diarrhea
- hemorrhage
What will direct cytotoxic effects cause?
- capillary leakage
- plasma loss
What neurological effects will iron toxicity have?
- lethargy and weakness are common in severe poisonings
- coma
How long is the Stage 1 (initial period) after ingestion?
0.5-6 hours post-ingestion
Describe symptoms of stage 1 toxicity (local toxicity)
- n/v/d
- gastroenteritis
- hematemesis
- ab pain
- melena
- lethargy
- hypotension
- tachycardia and tachypnea (may be present)
How long is the Stage 2 (latent period) after ingestion?
6-24 hours
What happens in Stage 2?
patient may recover or progress to stage 3
How long is the Stage 3 (period of systemic toxicity?)
4-40 hours
What happens in Stage 3?
- pallor or cyanosis
- lethargy
- hypotension
- disorientation
- convulsions
- coma
- shock
- coagulopathy
- fever
- leukocytosis
- hyperglycemia
- metabolic acidosis
How long is stage 4 after ingestion?
2-4 days
What happens in Stage 4?
- jaundice
- hypoglycemia
- elevated transaminases
- prolonged clotting times
- thrombocytopenia
- hemorrhage
- renal failure
- pulmonary edema
How long is stage 5 (late complications) after ingestion?
2-8 weeks
What happens in stage 5?
- GI obstruction
- pyloric stenosis secondary to scarring
- gastric fibrosis
- strictures
Management:
What dose is usually asymptomatic?
< 20mg/kg
Management:
What dose may produce self-limiting vomiting and diarrhea?
20-30 mg/kg
Management:
What dose is potentially serious?
> 40mg/kg
Management:
What dose is potentially lethal?
> 60mg/kg
Management:
Refer children with a dose of ____ to an emergency facility
> 10 mg/kg
What is the lowest reported lethal dose in a child?
600 mg
Describe the diagnosis of iron toxicity
- History of exposure
- Presence of vomiting, diarrhea, hypotension
- Laboratory involvement
- Abdominal radiograph
What is a normal Fe serum level?
80-180 mcg/dL
Iron toxicity is associated with values > _____
350 mcg/dL
What is the “action” level?
> 500 mcg/dL
What interventions are appropriate for iron toxicity?
- ABC
- Basic life support
- Gastric emptying (gastric lavage or whole-bowel irrigation)
- Chelators
Why is activated charcoal not useful?
metals are not really absorbed well by AC
What is DFO (deferoxamine mesylate) ?
A specific iron-binding ligand
What does DFO do?
chelates free iron and the iron of ferritin
*does not affect iron bound to hemoglobin or cytochromes!!
What is Ferrioxamine?
iron/DFO complex
Iron/DFO complex is _____
non-toxic
Iron/DFO complex is excreted in the urine as what color?
orange, pink or brown
How much DFO equals iron??
100mg DFO = 9mg iron
How is DFO administered?
IV, IM or SC
*iv is recommended
What is the dose of DFO?
- Initial dose of 90mg/kg IM
- Max 1 g in children, 2g in adults
-Subsequent IM dosing of 90mg/kg (to a max of 2g) at 4-12 hour intervals depending on serum iron levels and urine color
OR
-constant IV infusion at a rate up to 15mg/kg/h
Why is IV therapy preferred to IM for DFO?
IV therapy removes several times more iron than IM
When do you d/c DFO therapy?
- Patient returns to an asymptomatic state after the presumed latent period has passed
- Serum iron is < 150 ug/dL
- Return to normal urine color
With DFO, need to ensure proper _____
hydration
Can DFO be used in pregnant patients?
yes
What are the general side effects of DFO?
- histamine release
- DFO-iron complex, growth factor for Yersinia enterocolitica
- Excessive intracellular chelation (oxidant damage)
What are the acute side effects of DFO?
- hypotension
- infections
- pulmonary toxicity
What are the chronic side effects of DFO?
- auditory/ocular toxicity
- pulmonary toxicity
- infections
