Lecture 1 - Dyshemoglobinemias Flashcards
At what oxidation state does hemoglobin-bound iron bind oxygen?
Ferrous state (2+)
Describe CO interaction with Hb
Binds 200-250X > oxygen, shifts oxygen curve to left, decrease 2,3 DPG (therefore difficult to release oxygen at tissue)
Describe CO toxicity of the heart
CO binds to myoglobin and results in myocardial toxicity
Describe CO toxicity of mitochondria
CO binds to cytochrome oxidase and inhibits cellular respiration. Effect exacerbated with hypoxia and hypotension.
Describe CO toxicity of platelets
CO displaces NO from platelets and forms peroxynitrites which result in free radical mediated damage which contributes to central nervous system long-term toxicity
Syx of acute mild CO toxicity
Headache, Nausea, Vomiting, Dizziness
Syx of acute moderate CO toxicity
Chest pain, blurred vision, dyspnea on exertion, tachycardia, tachypnea, cognitive deficits, myonecrosis, ataxia
Syx of acute severe CO toxicity
Seizures, coma, dysrythmias, hypotension, MI/ischemia, skin bullae
Late/Chronic Effects of CO toxicity
Cognitive dysfunction, dementia, psychosis, amnesia, parkinsonism, paralysis chorea, cortical blindness, apraxia, agnosias, peripheral neuropathy, incontinence
Mechanism of Late CO toxicity effects
Reperfusion injury - During recovery WBCs adhere to brain microvasculature, release proteases, convert xanthine dehydrogenase to xanthine oxidase -> free radical formation -> lipid peroxidation
CO toxicity patient evaluation
Look for end organ manifestations of toxicity (CNS, cardiac, perfusion), check oxygen levels
When evaluating a patient who presents with CO poisoning, what should you be aware of when analyzing oxygen levels?
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.
Tx for CO toxicity
Airway, Breathing, Circulation (ABCs) and oxygen, and possibly Hyperbaric oxygen
How does administering oxygen and placing a patient in a hyperbaric oxygen chamber effect t1/2 of CO?
T1/2 of CO goes from 2-7 hrs to 30-150 min (oxygen) or 4-86 min (hyperbaric oxygen)
Sources of cyanide
Gas (chemical warfare/fires) or crystals (jewelers, electroplating, house fires
Cyanide toxicity mechanism of action
Binds to cytochrome A3 on electron transport chain and therefore no ATP production
Tx for CN toxicity
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)
Indications to use Hydroxocobalamin
Any smoke inhalation victim not improving despite O2 care, intentional CN exposure
What is metHb?
Heme iron oxidized to ferric (3+) form
Name 4 methods in which oxidants are reduced to protect Hb(2+)
Catalase (formation of H2O), Glutathione, Sulfhydryl, Ascorbate
Name 4 methods by which metHb(3+) is reduced to Hb(2+)
Ascorbate, NADH metHb Reductase (coenzyme B), Glutathione, NADPH metHb reductase (methylene blue)
Syx of metHb toxicity
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
Oxygen saturation analysis of CN poison patient
Pulse oximetry - falsely and abberantly low
CO-oximeter - appropriate readings
Arterial Blood Gas - Falsely normal because pO2 is not effected
Tx for CN poisoning patient
ABC’s, decontamination, methylene blue is mjr antidote, minor antidotes - n-acetylcysteine, exchange transfusion, hyperbaric oxygen
Causes of metHb
Nitrites most frequent, Nitrates in infants
Mechanism for methylene blue antidote
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.
Indications and cautions of methylene blue to treat
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
Conditions in which methylene blue fails to treat metHbemia
Hemoglobin M disease, G6PD deficiency (can’t make enough NADPH to regenerate metHb reductase
What is the treatment and cure for sulfhemoglobinemia?
There is no cure, only supportive treatment
