Unit 2 - Dyshemoglobinemia Flashcards Preview

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Flashcards in Unit 2 - Dyshemoglobinemia Deck (39):

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?

1. incomplete combustion of carbon containing material
-gasses: methane VS coal VS gasoline
2. internal production (minimal, only if ingest/inhale methyline Cl)


explain the entry/exit of CO (pharmacokinetics)

1. absorption/excretion
-CO gains entry through respiration
-methylene cloride is converted to CO in vivo only
2. 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?

1. mitochondrial cytochrome oxidase binding
-increased with hypoxia and hypotension
2. 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?

1. ABC's, O2 to shorten CO half-life (from 2-7 hr to 30-150 min)
2. 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?

1. loss of consciousness
-syncope, coma, seizures
2. GCS < 15 on presentation
3. CO level > 10%
4. MI, ventricular dysrhythmias
5. 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?

1. lactate > 10 mmol/L
2. patient doesn't respond to supportive care


what are the forms of cyanide?

1. gas (usually chemical warfare/industrial accidents)
2. 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?

1. ABCs, supportive care, ACLS, largely not successful
2. cyanide antidote kit/package (sodium/amyl nitrite)
3. hydroxocobalamin
-binds with cyanide to make cyanocobalamin (B12)
4. HBO +/0


when and how should one treat with hydroxocobalamin?

1. any smoke-inhalation victim that is NOT improving despite supportive care including O2
2. 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?

1. rate of heme oxidation increases
2. reduction of heme is limited
3. structural abnormalities of heme


what are causes of methemoglobinemia?

1. congenital
2. infantile disposition
3. external causes


how does methemoglobin exert its toxicity?

1. incapacitates O2 transport
2. shifts O2 dissociation curve to left


what are symptoms of methemoglobin at:

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?

1. co-oximeter will be appropriate
2. calculation will be falsely normal b/c pO2 is not affected


what are drugs that give methemoglobinemia?

1. nitrites (major)
2. nitrates in infants (major)
3. sulfonamides
4. phenazopyridine
5. dapsone
6. local anesthetics

these cause oxidant stress


what are toxins that give methemoglobinemia?

1. nitrites (major)
2. nitrates in infants (major)
3. aniline dye
4. potassium chlorate
5. diarrheal illness in infants (make nitrites; major)


what is treatment for methemoglobinemia?

1. ABC's
2. decontamination
3. methylene blue (tetramethyl tionine chloride; specific antidote)
-minor antidotes and in non-responders to methylene blue
--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?

1. hemolytic anemia from weak oxidizing capability
2. painful at injection site (dysuria)
3. higher doses can cause dyspnea, restlessness, tremor, precordial pain, apprehension


what are possible reasons for methylene blue non-responders?

1. hemoglobin M disease
2. G6PD deficiency - lack generation of NADPH dependent methemoglobin reducase
3. CL salts inactivating G6PD
4. sulfhemoglobinemia
-more benign, levels up to 10 g/dL don't cause cyanosis
5. 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