Lecture 1 - Dyshemoglobinemias

Question 1

At what oxidation state does hemoglobin-bound iron bind oxygen?

Answer 1

Ferrous state (2+)

Question 2

Describe CO interaction with Hb

Answer 2

Binds 200-250X > oxygen, shifts oxygen curve to left, decrease 2,3 DPG (therefore difficult to release oxygen at tissue)

Question 3

Describe CO toxicity of the heart

Answer 3

CO binds to myoglobin and results in myocardial toxicity

Question 4

Describe CO toxicity of mitochondria

Answer 4

CO binds to cytochrome oxidase and inhibits cellular respiration. Effect exacerbated with hypoxia and hypotension.

Question 5

Describe CO toxicity of platelets

Answer 5

CO displaces NO from platelets and forms peroxynitrites which result in free radical mediated damage which contributes to central nervous system long-term toxicity

Question 6

Syx of acute mild CO toxicity

Answer 6

Headache, Nausea, Vomiting, Dizziness

Question 7

Syx of acute moderate CO toxicity

Answer 7

Chest pain, blurred vision, dyspnea on exertion, tachycardia, tachypnea, cognitive deficits, myonecrosis, ataxia

Question 8

Syx of acute severe CO toxicity

Answer 8

Seizures, coma, dysrythmias, hypotension, MI/ischemia, skin bullae

Question 9

Late/Chronic Effects of CO toxicity

Answer 9

Cognitive dysfunction, dementia, psychosis, amnesia, parkinsonism, paralysis chorea, cortical blindness, apraxia, agnosias, peripheral neuropathy, incontinence

Question 10

Mechanism of Late CO toxicity effects

Answer 10

Reperfusion injury - During recovery WBCs adhere to brain microvasculature, release proteases, convert xanthine dehydrogenase to xanthine oxidase -> free radical formation -> lipid peroxidation

Question 11

CO toxicity patient evaluation

Answer 11

Look for end organ manifestations of toxicity (CNS, cardiac, perfusion), check oxygen levels

Question 12

When evaluating a patient who presents with CO poisoning, what should you be aware of when analyzing oxygen levels?

Answer 12

When using pulse oximetry, you may get a falsely normal oxygen reading because carboxyHb is read as oxyHb. When using arterial blood gas, you may get a false normal reading because ABG measures dissolved O2. There may be an extremely high level of dissolved CO in the blood. CO-oximeters are ideal because they can measure the concentrations of carboxyHb, oxyHb, metHb, and reducedHb.

Question 13

Tx for CO toxicity

Answer 13

Airway, Breathing, Circulation (ABCs) and oxygen, and possibly Hyperbaric oxygen

Question 14

How does administering oxygen and placing a patient in a hyperbaric oxygen chamber effect t1/2 of CO?

Answer 14

T1/2 of CO goes from 2-7 hrs to 30-150 min (oxygen) or 4-86 min (hyperbaric oxygen)

Question 15

Sources of cyanide

Answer 15

Gas (chemical warfare/fires) or crystals (jewelers, electroplating, house fires

Question 16

Cyanide toxicity mechanism of action

Answer 16

Binds to cytochrome A3 on electron transport chain and therefore no ATP production

Question 17

Tx for CN toxicity

Answer 17

ABC’s, supportive care
Cyanide antidote kit
1) Nitrites for metHb (Dangerous in concurrent CO poisoning
2)Sodium Thiosulfate - enhance CN metabolism
3)Hydroxocobalamin (Vitamin B12a) - binds with CN to make cyanocobalamin (B12)

Question 18

Indications to use Hydroxocobalamin

Answer 18

Any smoke inhalation victim not improving despite O2 care, intentional CN exposure

Question 19

What is metHb?

Answer 19

Heme iron oxidized to ferric (3+) form

Question 20

Name 4 methods in which oxidants are reduced to protect Hb(2+)

Answer 20

Catalase (formation of H2O), Glutathione, Sulfhydryl, Ascorbate

Question 21

Name 4 methods by which metHb(3+) is reduced to Hb(2+)

Answer 21

Ascorbate, NADH metHb Reductase (coenzyme B), Glutathione, NADPH metHb reductase (methylene blue)

Question 22

Syx of metHb toxicity

Answer 22

Shift oxygen curve to left
0-10% - asymptomatic
10-20% - Apparent cyanosis
20-50% - dizziness, fatigue, headache, exertional dyspnea
>50% - stupor
>70% - coma and death

Question 23

Oxygen saturation analysis of CN poison patient

Answer 23

Pulse oximetry - falsely and abberantly low
CO-oximeter - appropriate readings
Arterial Blood Gas - Falsely normal because pO2 is not effected

Question 24

Tx for CN poisoning patient

Answer 24

ABC’s, decontamination, methylene blue is mjr antidote, minor antidotes - n-acetylcysteine, exchange transfusion, hyperbaric oxygen

Question 25

Causes of metHb

Answer 25

Nitrites most frequent, Nitrates in infants

Question 26

Mechanism for methylene blue antidote

Answer 26

MB reduces metHb; MB is regenerated by metHb reductase which is regenerated with NADPH produced by G6PD. This pathway is rarely used but utilized by physicians.

Question 27

Indications and cautions of methylene blue to treat

Answer 27

metHb levels >20-30% or symptoms
Cautions: Hemolytic anemia, painful injection site, higher doses of MB result in dyspnea, restlessness, tremor, precordial pain, and apprehension

Question 28

Conditions in which methylene blue fails to treat metHbemia

Answer 28

Hemoglobin M disease, G6PD deficiency (can’t make enough NADPH to regenerate metHb reductase

Question 29

What is the treatment and cure for sulfhemoglobinemia?

Answer 29

There is no cure, only supportive treatment