Lecture 6 - Iron

Question 1

Why are we only dealing with treatment of acute iron toxicity?

Answer 1

chronic toxicity usually doesn’t happen, we don’t absorb more than what we need unless you take a bunch at once (acute)

Question 2

What is iron commonly used for?

Answer 2

• anemia
• prenatal supplement
• daily nutritional supplement

Question 3

Absorption of iron is an active process regulated by the level of body iron stores and demands for ________

Answer 3

erythropoiesis (production of red blood cells)

Question 4

_____ iron is absorbed into the mucosal cell (duodenum and jejunum) and is oxidized to ferric iron

Answer 4

ferrous

Question 5

____ iron is more available for absorption than inorganic forms of iron

Answer 5

heme

Question 6

What is the daily intake or iron?

Answer 6

10-20mg

Question 7

How much is actually absorbed from 10-20mg?

Answer 7

1-2 mg

Question 8

In plasma, iron is bound to ______

Answer 8

transferrin

Question 9

Transferrin system is normally ___ saturated

Answer 9

1/3

Question 10

T or F: normally there is free iron present in serum

Answer 10

False: normally there is no free iron present in serum

Question 11

In overdose, the acute corrosive effect of iron on the GIT mucosa ______ absorption and the transferrin system may become saturated.

Answer 11

enhances

Question 12

In tissue, iron is stored as ______

Answer 12

ferritin

Question 13

Is there a physiologic mechanism for iron excretion?

Answer 13

No

Question 14

How will the body try and excrete iron?

Answer 14

• sweat
• bile
• desquamation of the skin and mucosal surfaces (sort of like peeling)

Question 15

What is the toxic dose of elemental iron?

Answer 15

10-20mg/kg of elemental iron

Question 16

What are some direct corrosive effects of iron on the gastric and intestinal mucosa?

Answer 16

ulceration, severe edema, hemorrhage, infarction, venous thrombosis

which leads to:

vomiting, abdominal pain, diarrhea, ulceration, hematemesis, melena

Question 17

hypovolemia = tissue perfusion = ______ _________

Answer 17

metabolic acidosis

Question 18

What do high ferritin levels do?

Answer 18

cause tissue damage and release of vasoactive substances

Question 19

Iron concentrates in the _______ which disrupts oxidative phosphorylation, free radical formation and lipid peroxidation which leads to cell death and tissue injury

Answer 19

mitochondria

Question 20

What are acute corrosive effects of iron toxicity?

Answer 20

perforation and peritonitis - which may enhance iron absorption

Question 21

How does iron cause hepatic toxicity?

Answer 21

Free iron concentrations in the hepatocyte during first absorptive pass will cause:

• electron transport abnormalities
• lactate production
• glycogen depletion
• enzymatic dysfunction

Question 22

What type of acid base disorder comes from iron toxicity?

Answer 22

metabolic acidosis

Question 23

How does iron toxicity affect blood sugar?

Answer 23

hyperglycemia

Question 24

With acute iron poisoning, hepatocellular toxicity may be severe. What will this cause?

Answer 24

• hyperbilirubinemia
• aminotransferase abnormalities
• coagulopathy
• diffused tissue necrosis
• disruption of normal metabolic pathways

Question 25

How will free iron affect CV toxicity?

Answer 25

- venodilation - CV compromise - shock

Question 26

What does acute volume loss from GIT cause?

Answer 26

- vomiting - diarrhea - hemorrhage

Question 27

What will direct cytotoxic effects cause?

Answer 27

- capillary leakage | - plasma loss

Question 28

What neurological effects will iron toxicity have?

Answer 28

- lethargy and weakness are common in severe poisonings | - coma

Question 29

How long is the Stage 1 (initial period) after ingestion?

Answer 29

0.5-6 hours post-ingestion

Question 30

Describe symptoms of stage 1 toxicity (local toxicity)

Answer 30

- n/v/d - gastroenteritis - hematemesis - ab pain - melena - lethargy - hypotension - tachycardia and tachypnea (may be present)

Question 31

How long is the Stage 2 (latent period) after ingestion?

Answer 31

6-24 hours

Question 32

What happens in Stage 2?

Answer 32

patient may recover or progress to stage 3

Question 33

How long is the Stage 3 (period of systemic toxicity?)

Answer 33

4-40 hours

Question 34

What happens in Stage 3?

Answer 34

- pallor or cyanosis - lethargy - hypotension - disorientation - convulsions - coma - shock - coagulopathy - fever - leukocytosis - hyperglycemia - metabolic acidosis

Question 35

How long is stage 4 after ingestion?

Answer 35

2-4 days

Question 36

What happens in Stage 4?

Answer 36

- jaundice - hypoglycemia - elevated transaminases - prolonged clotting times - thrombocytopenia - hemorrhage - renal failure - pulmonary edema

Question 37

How long is stage 5 (late complications) after ingestion?

Answer 37

2-8 weeks

Question 38

What happens in stage 5?

Answer 38

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

Question 39

Management: What dose is usually asymptomatic?

Answer 39

< 20mg/kg

Question 40

Management: What dose may produce self-limiting vomiting and diarrhea?

Answer 40

20-30 mg/kg

Question 41

Management: What dose is potentially serious?

Answer 41

> 40mg/kg

Question 42

Management: What dose is potentially lethal?

Answer 42

> 60mg/kg

Question 43

Management: Refer children with a dose of ____ to an emergency facility

Answer 43

> 10 mg/kg

Question 44

What is the lowest reported lethal dose in a child?

Answer 44

600 mg

Question 45

Describe the diagnosis of iron toxicity

Answer 45

- History of exposure - Presence of vomiting, diarrhea, hypotension - Laboratory involvement - Abdominal radiograph

Question 46

What is a normal Fe serum level?

Answer 46

80-180 mcg/dL

Question 47

Iron toxicity is associated with values > _____

Answer 47

350 mcg/dL

Question 48

What is the "action" level?

Answer 48

> 500 mcg/dL

Question 49

What interventions are appropriate for iron toxicity?

Answer 49

- ABC - Basic life support - Gastric emptying (gastric lavage or whole-bowel irrigation) - Chelators

Question 50

Why is activated charcoal not useful?

Answer 50

metals are not really absorbed well by AC

Question 51

What is DFO (deferoxamine mesylate) ?

Answer 51

A specific iron-binding ligand

Question 52

What does DFO do?

Answer 52

chelates free iron and the iron of ferritin *does not affect iron bound to hemoglobin or cytochromes!!

Question 53

What is Ferrioxamine?

Answer 53

iron/DFO complex

Question 54

Iron/DFO complex is _____

Answer 54

non-toxic

Question 55

Iron/DFO complex is excreted in the urine as what color?

Answer 55

orange, pink or brown

Question 56

How much DFO equals iron??

Answer 56

100mg DFO = 9mg iron

Question 57

How is DFO administered?

Answer 57

IV, IM or SC *iv is recommended

Question 58

What is the dose of DFO?

Answer 58

- 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

Question 59

Why is IV therapy preferred to IM for DFO?

Answer 59

IV therapy removes several times more iron than IM

Question 60

When do you d/c DFO therapy?

Answer 60

- Patient returns to an asymptomatic state after the presumed latent period has passed - Serum iron is < 150 ug/dL - Return to normal urine color

Question 61

With DFO, need to ensure proper _____

Answer 61

hydration

Question 62

Can DFO be used in pregnant patients?

Answer 62

yes

Question 63

What are the general side effects of DFO?

Answer 63

- histamine release - DFO-iron complex, growth factor for Yersinia enterocolitica - Excessive intracellular chelation (oxidant damage)

Question 64

What are the acute side effects of DFO?

Answer 64

- hypotension - infections - pulmonary toxicity

Question 65

What are the chronic side effects of DFO?

Answer 65

- auditory/ocular toxicity - pulmonary toxicity - infections