Unit 2 - Dyshemoglobinemia Flashcards
explain what hemoglobin is and its purpose
conjugated protein (64,500 D)
- two pairs of polypeptide chains (4 heme molecules attached total)
- for tissue perfusion
what is heme’s structure?
Fe complexed at the center of a porphyrin ring
- ferrous state (2+) of the Fe carries O2, CO
- globin chain protects Fe moiety from inappropriate oxidation
difference between carboxyhemoglobin, oxyhemoglobin, and methemoglobin?
carboxy = CO oxy = O2 met = O2, but heme Fe in +3 form
what are sources of CO?
- incomplete combustion of carbon containing material
- gasses: methane VS coal VS gasoline - internal production (minimal, only if ingest/inhale methyline Cl)
explain the entry/exit of CO (pharmacokinetics)
- absorption/excretion
- CO gains entry through respiration
- methylene cloride is converted to CO in vivo only - distribution
- via hemoglobin, myoglobin, etc.
explain CO pharmacology?
binds to Hb (200-250 x O2)
- shifts O2 dissociation curve to the left
- decrease in RBC 2,3-DPG
explain the mechanism of CO?
- mitochondrial cytochrome oxidase binding
- increased with hypoxia and hypotension - NO displaced from platelets from peroxynitrites
explain the mild, moderate, and severe effects of CO?
mild: HA, nausea/vomiting, dizziness
moderate: cheset pain, blurred vision, dyspnea on exertion, tachycardia, tachypnea, cognitive deficits, myonecrosis, ataxia
severe: seizures, coma, dysrhythmias, hypotension, MI/ischemia, skin bullae
what are “late/chronic effects” of CO? when do they occur?
- cognitive dysfunction
- dementia, psychosis, amnesia
- parkinsonism, paralysis chorea, cortical blindness, apraxia, agnosias, peripheral neuropathy, incontinence
these are preceded by a “lucent” period of 2-40 days, meaning it can seem like a patient got better, but then has these effects
what is the theory behind the mechanism of late effects of CO?
reperfusion injury
- during recovery, WBC are attracted and adhere to brain microvasculature due to cyclooxygenase dysfunction (?)
- WBCs release proteases, convert xanthine dehydrogenase to xanthine oxidase, promoting FR formation, leading to delayed lipid peroxidation
at what ages are adults at greatest risk?
> 30 yo
how should one evaluate CO poisoning?
look for end-organ manifestations of toxicity
- CNS, cardiac, perfusion
- CO level is of relative importance
what is pulse oximetry in CO poisoning?
falsely normal
-carboxyhemoglobin is read as oxyhemoglobin
what is arterial blood gas in CO poisoning?
co-oximeter will be appropriate
calculation will be falsely normal b/c pO2 is not affected
what is treatment for CO poisoning?
- ABC’s, O2 to shorten CO half-life (from 2-7 hr to 30-150 min)
- hyperbaric O2 under pressure (HBO)
- shortens half-life to 4-86 minutes, increases O2
- prevents lipid peroxidaiton in animal models
what are indications for HBO?
- loss of consciousness
- syncope, coma, seizures - GCS < 15 on presentation
- CO level > 10%
- MI, ventricular dysrhythmias
- neurologic signs 2-4 hours out
what are some neuroanatomical side effects of CO?
bilateral low density areas of globus pallidus, putamen, and caudate nuclei
-rarely seen
how does one “pick out” cyanide poisoning?
- lactate > 10 mmol/L
2. patient doesn’t respond to supportive care
what are the forms of cyanide?
- gas (usually chemical warfare/industrial accidents)
- crystal (requires mucous membranes or po exposure)
- jewelers, electroplating, other industries, house fires
where does cyanide bind?
cytochrome A3 on ETC
-rapid onset of multi-system organ failure (no ATP)
what is treatment for cyanide?
- ABCs, supportive care, ACLS, largely not successful
- cyanide antidote kit/package (sodium/amyl nitrite)
- hydroxocobalamin
- binds with cyanide to make cyanocobalamin (B12) - HBO +/0
when and how should one treat with hydroxocobalamin?
- any smoke-inhalation victim that is NOT improving despite supportive care including O2
- any intentional cyanide exposure
- 5 g dose, can be repeated x1
- give concurrently with sodium thiosulfate
- may cause increased BP
what is the mechanism of sodium/amyl nitrite in cyanide poisoning?
sodium/amyl nitrite makes met-Hb, so the CN (and H2S, if any) bind to met-Hb instead of cytochromes
- these cyanomet-Hb or SHmet-Hb are then excreted
- -cyanometHb needs thiosulfate to be excreted
define what methemoglobin is?
heme Fe oxidized to ferric (+3) form
-normal amounts 1-3%
what is the mechanism of methemoglobinemia?
- rate of heme oxidation increases
- reduction of heme is limited
- structural abnormalities of heme
what are causes of methemoglobinemia?
- congenital
- infantile disposition
- external causes
how does methemoglobin exert its toxicity?
- incapacitates O2 transport
2. shifts O2 dissociation curve to left
what are symptoms of methemoglobin at: 0-10% 10-20% 20-50% >50% >70%
0-10%: asymptomatic 10-20% apparent cyanosis 20-50% dizziness, fatigue, HA, exertional dyspnea >50% lethargy/stupor >70% coma/death
what is pulse oximetry in methemoglobin?
falsely and aberrantly lowered
-measured as both oxy and deoxyhemoglobin, will fall rapidly into high 80s
what is arterial blood gas in methemoglobin?
- co-oximeter will be appropriate
2. calculation will be falsely normal b/c pO2 is not affected
what are drugs that give methemoglobinemia?
- nitrites (major)
- nitrates in infants (major)
- sulfonamides
- phenazopyridine
- dapsone
- local anesthetics
these cause oxidant stress
what are toxins that give methemoglobinemia?
- nitrites (major)
- nitrates in infants (major)
- aniline dye
- potassium chlorate
- diarrheal illness in infants (make nitrites; major)
what is treatment for methemoglobinemia?
- ABC’s
- decontamination
- methylene blue (tetramethyl tionine chloride; specific antidote)
- minor antidotes and in non-responders to methylene blue
- -N-acetylcysteine
- -exchange transfusion
- -hyperbaric O2
explain the mechanism of methylene blue
used in treatment of methemoglobinemia
- cofactor of NADPH reductase
- gains electron, then donates directly to methemoglobin
- methemoglobin reduction to (Fe 2+)
when is methylene blue treatment indicated?
if methemoglobin level >20-30%, or symptoms
what are cautions in using methylene blue?
- hemolytic anemia from weak oxidizing capability
- painful at injection site (dysuria)
- higher doses can cause dyspnea, restlessness, tremor, precordial pain, apprehension
what are possible reasons for methylene blue non-responders?
- hemoglobin M disease
- G6PD deficiency - lack generation of NADPH dependent methemoglobin reducase
- CL salts inactivating G6PD
- sulfhemoglobinemia
- more benign, levels up to 10 g/dL don’t cause cyanosis - wrong diagnosis
what is sulfhemoglobinemia?
symptoms similar to methemoglobinemia
- methemoglobin levels will be elevated
- laboratory can “tease out” by adding cyanide to blood
- treatment is supportive only
what are causes of sulfhemoglibnemia?
acetanilid, phenacitin, nitrites, trinitrotoluene, sulfur
